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Jiang, Zhang. "Distinguishing between “Jie” and “Shi”." Social Sciences in China 41, no. 3 (July 2, 2020): 5–33. http://dx.doi.org/10.1080/02529203.2019.1674034.
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Harris, Amanda, Suzanne Belton, Lesley Barclay, and Jenny Fenwick. "Midwives in China: ‘jie sheng po’ to ‘zhu chan shi’." Midwifery 25, no. 2 (April 2009): 203–12. http://dx.doi.org/10.1016/j.midw.2007.01.015.
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이승신. "A Study on Guaishuo(怪說) Written by Shi, jie(石介)." JOURNAL OF CHINESE STUDIES ll, no. 61 (September 2018): 77–98. http://dx.doi.org/10.26585/chlab.2018..61.004.
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Eckfeld, Tonia. "Modeling Peace: Royal Tombs and Political Ideology in Early China by Jie Shi." China Review International 26, no. 3 (2019): 201–3. http://dx.doi.org/10.1353/cri.2019.0034.
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Bujard, Marianne. "Modeling Peace. Royal Tombs and Political Ideology in Early China, by Jie Shi." T’oung Pao 108, no. 1-2 (March 31, 2022): 237–47. http://dx.doi.org/10.1163/15685322-10801001.
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Na, Min-gu, and Ming-jie Dan. "Rhetorical Analysis on "Piao Tong Shi Yan Jie" --Value in Writing and Reading." Journal of Chinese Studies 86 (November 30, 2018): 199–222. http://dx.doi.org/10.36493/jcs.86.8.
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Pan, Tao. "Tocharian A ārkiśoṣi ‘world with radiance’ and Chinese suo po shi jie ‘world of sabhā’." Acta Asiatica Varsoviensia 34 (2021): 263–94. http://dx.doi.org/10.60018/acasva.abdn5783.
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This article provides an explanation for the single and puzzling Tocharian B gloss śaiṣṣe ‘world’ (instead of Tocharian A ārkiśoṣi) for Sanskrit jagat- ‘world’ on a Sanskrit fragment SHT 4438 with all the other glosses in Tocharian A. Based on a detailed study of the Sanskrit and Chinese texts, Tocharian A ārkiśoṣi is very likely the loan translation of Sanskrit sā̆bhāloka(dhātu)- ‘a world with radiance’, which is preserved in the Chinese translations by Kumārajīva and other translators connected with Kucha. In the Kucha area, the first part sā̆bhā- was understood as containing -(ā)bhā- ‘radiance’. Buddhist Sanskrit sa(b)hāloka(dhātu)- is built from sa(b)hāpati- ‘master of sa(b)hā world’, epithet of the highest divinity Brahmā in the sahāloka-, which derives via Middle Indic from the older epithet sabhāpati- ‘owner of the assembly hall’ in Atharvaveda. The excursus at the end offers a glimpse into the complicated transmission process of Chinese Buddhist terminology based on the analysis of Chinese sha men ‘monk’ and he shang ‘teacher, monk’.
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CIM, Editor. "Letter of Retraction." Clinical & Investigative Medicine 38, no. 3 (May 31, 2015): 142. http://dx.doi.org/10.25011/cim.v38i3.22708.
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It has come to our attention that the a manuscript published in CIM: JianXin J, Cha Y, ZhiPeng L, Jie X, Hao Z, Meiyuan C, ChengYi S “GOLP3 is a predictor of survival in patients with hepatocellular carcinoma” Clin Invest Med. 2014 Aug 1;37(4):E233-42 contains text identical to a manuscript published in Tumour Biology: Hu GS, Li YQ, Yang YM, Shi W, Liao AJ, Yao YH, Zeng B, Yuan J “High expression of Golgi phosphoprotein-3 is associated with poor survival in patients with hepatocellular carcinoma” Tumour Biol. 2014 Sep;35(9):8625-32. doi: 10.1007/s13277-014-2105-8. Epub 2014 May 28. For this reason, the publication in CIM has been retracted. Jonathan Angel, MD Editor, CIM
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Sheng, Kai, and Bangwei Zhou. "“Interpreting Buddhist Precepts with Confucian Rites” Based on Their Similarity and Dissimilarity: A Perspective of the History of Ideas in Wei, Jin, and Northern and Southern Dynasties." Religions 13, no. 11 (November 9, 2022): 1081. http://dx.doi.org/10.3390/rel13111081.
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The “similarity” (gongtong 共通) and “dissimilarity” (chayi 差異) between the Buddhist precepts and Confucian rites in the Wei, Jin, and Southern and Northern Dynasties reflected a “dialogue of civilizations” (wenming duihua 文明對話) at the levels of concept, system, and life. During these periods, the Chinese system of rites were compared and interpreted with the Buddhist monastic codes by Buddhist monks and Confucian scholars, so a history of the ideas interpretation process of “interpreting precepts with rites” (yi li shi jie 以禮釋戒) was achieved. The result of such a process was two-fold: from the perspective of lay Buddhist ethics, they were in common with each other; from the perspective of monastic precepts, they were irreconcilable contradictions. Thus, on the one hand, the eminent Chinese monks “were emulating the Confucian rites to justify Buddhist precepts” (ni li yi zheng jie 擬禮義證戒) to stress their commonalities. On the other hand, the differences between the precepts and rites continued to be discovered, and the Buddhist subjective consciousness (zhuti yishi 主體意識) of “the distinction between precepts and rites” (jie li you bie 戒禮有別) was gradually established.
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Shi, Jie, Rui Zhou, Shuo Wang, Yuxin Liu, Baorui Tian, Yanhua Liu, YaNan Chen, et al. "Abstract 1564: NEU4-mediated desialylation ignites the oncogenic receptors for the dissemination of ovarian carcinoma." Cancer Research 84, no. 6_Supplement (March 22, 2024): 1564. http://dx.doi.org/10.1158/1538-7445.am2024-1564.
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Abstract Background: Glycosylation profoundly influences the interactions between cancer cells and microenvironmental stromal cells during the peritoneal disseminated metastasis of ovarian carcinoma (OC), which is the major cause of cancer-related death. Although the characteristic cancer glycoconjugates are widely used as biomarkers for cancer diagnosis, our knowledge about cancer glycome remains quite fragmented due to the technique limitations in analyzing glycan chains with tremendous structural and functional heterogeneity. Method: Given the dysregulated cancer glycome is defined by the altered glycosylation machinery, here we performed a systematic loss-of-function screen on 498 genes involved in glycosylation for key regulators of OC dissemination. We identified neuraminidase 4 (NEU4), an enzyme capable of hydrolyzing terminal sialic acid from glycoconjugates, as a vital peritoneal dissemination-promoting modifier of OC glycome. What’s more, we also identified membrane proteins whose sialylation was able to be modified by NEU4 in OC cells by pull down and mass spectrum to investigate the functional significance of NEU4-mediated desialylation. Results: In human patients with high-grade serous OC (HGSOC), increased NEU4 was detected in the disseminated OC cells when compared with that in the primary tumor cells, which significantly correlated with the worse survival. Among three alternative splice-generated isoforms of human NEU4, we revealed that only the plasma membrane-localized NEU4 isoform 2 (NEU4-iso2) and intracellular isoform 3 promoted the peritoneal dissemination of OC by enhancing the cell motility and epithelial-mesenchymal transition. We also identified NEU4-iso2-regulated cell surface glycoproteome and found that NEU4-iso2 desialylated the epithelial growth factor receptor (EGFR), in particular at N196 residue, for the hyperactivation of EGFR and its downstream tumor-promoting signaling cascades. Conclusion: Our results provide new insights into how the OC glycome is dysregulated by NEU4 during OC progression and reveals a functionally important glycosite on EGFR for its abnormal activation in cancer. Citation Format: Jie Shi, Rui Zhou, Shuo Wang, Yuxin Liu, Baorui Tian, Yanhua Liu, YaNan Chen, Taoyu Hu, Yuhao Mu, Shufan Wang, Xintao Shao, Jie Yan, Pengpeng Qu, Wei Ding, Shuang Yang, Yi Shi, Jia Li, Longlong Wang. NEU4-mediated desialylation ignites the oncogenic receptors for the dissemination of ovarian carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1564.
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Pan, Jianguo. "A new perspective on Pu Tong Shi Yan Jie and its quotations from the Journay to the west." Han Mun Hak Bo 42 (June 30, 2020): 285–318. http://dx.doi.org/10.35496/han.42.10.
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Li, Qing-Jie, Xue-Liang Fang, Ying-Qin Li, Jia-Yi Lin, Cheng-Long Huang, Shi-Wei He, Sheng-Yan Huang, et al. "Abstract 1999: DCAF7 acts as a scaffold to recruit USP10 for G3BP1 deubiquitylation and facilitates chemoresistance and metastasis in nasopharyngeal carcinoma." Cancer Research 84, no. 6_Supplement (March 22, 2024): 1999. http://dx.doi.org/10.1158/1538-7445.am2024-1999.
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Abstract Though docetaxel plus cisplatin and 5-fluorouracil (TPF) induction chemotherapy becomes the standard care for locoregionally advanced nasopharyngeal carcinoma (NPC), some patients could not benefit from this therapy. The underlying mechanisms remain unclear. We found that DCAF7 was highly expressed in TPF resistant NPC patients, and promoted the cisplatin resistance and metastasis of NPC cells. Mechanistically, DCAF7 facilitates the interaction between USP10 and G3BP1, resulting in the removal of K48-linked ubiquitylation of G3BP1 at Lys76 mediated by USP10, thus preventing the degradation of G3BP1 through ubiquitin-proteasome pathway, and facilitates the stress granule (SG)-like structures formation. Moreover, knockdown of G3BP1 successfully reversed the SG-like structures formation and oncogenic effects exerted by DCAF7. Importantly, NPC patients with elevated DCAF7 expression exhibited high risks of metastasis, and is associated with a poor prognosis. This study identifies DCAF7 as a pivotal cisplatin resistance gene, and sheds light on the underlying mechanism of TPF resistance in NPC patients. The DCAF7-USP10-G3BP1 axis provides potential therapeutic targets and biomarker for NPC treatment. Citation Format: Qing-Jie Li, Xue-Liang Fang, Ying-Qin Li, Jia-Yi Lin, Cheng-Long Huang, Shi-Wei He, Sheng-Yan Huang, Jun-Yan Li, Sha Gong, Kai-Lin Chen, Na Liu, Jun Ma, Yin Zhao, Ling-Long Tang. DCAF7 acts as a scaffold to recruit USP10 for G3BP1 deubiquitylation and facilitates chemoresistance and metastasis in nasopharyngeal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1999.
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Robinson, Ryen, and Christian DesRochers. "“Voluntary Termination of Life Insurance Policies: Evidence from the U.S. Market,” Shi-jie Jiang, Vol. 14, No. 3, 2010." North American Actuarial Journal 15, no. 3 (July 2011): 468–71. http://dx.doi.org/10.1080/10920277.2011.10597631.
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Bianchi, Ester. "Yi jie wei shi以戒為師: theory and practice of monastic discipline in modern and contemporary Chinese Buddhism." Studies in Chinese Religions 3, no. 2 (April 3, 2017): 111–41. http://dx.doi.org/10.1080/23729988.2017.1378004.
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Rudenko, N. V. "“Interpretation of Voidness and Fullness” and “Interpretation of Loftiness and Cleanliness”: Li Zhi’s Essays on the Qualities of Human Character." Orientalistica 3, no. 1 (March 29, 2020): 84–109. http://dx.doi.org/10.31696/2618-7043-2020-3-1-84-109.
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The paper continues the research of the chapter “Diverse Writings” (Za shu 雜述) of the famous “Book to Burn” (Fen shu 焚書), opus magnum of iconoclastic late Ming thinker Li Zhi (李贄, 1527–1602), and presents the first Russian translations of Li Zhi’s essays on qualities of human character: “Interpretation of Voidness and Fullness” (Xu shi shuo 虛實說) and “Interpretation of Loftiness and Cleanliness” (Gao jie shuo 高潔說). In these writings the thinker makes accent on the importance of real, not only nominal possession of virtues as well as of the ability to reconsider one’s own wrong views. He also protests against the hypocrisy and prejudice and puts forward the genuineness as a criteria of what makes the difference between ordinary people and a gentleman. The essays provide a bright reflection of the core features of Li Zhi’s philosophical views, such as oppositional authentism, naturalistic dualism and the synthesis of Buddhist, Daoist and Confucian elements.The author declares that there is no conflict of interest.
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Yang, Huiqin, Dehong Ma, Qin Li, Wen Zhou, Hongyi Chen, Xiyun Shan, Haipeng Zheng, et al. "Real-World Study on Chai-Shi-Jie-Du Granules for the Treatment of Dengue Fever and the Possible Mechanisms Based on Network Pharmacology." Evidence-Based Complementary and Alternative Medicine 2023 (August 30, 2023): 1–12. http://dx.doi.org/10.1155/2023/9942842.
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Objectives. Traditional Chinese medicine (TCM) is a widely used method for treating dengue fever in China. TCM improves the symptoms of patients with dengue, but there is no standard TCM prescription for dengue fever. This real-world study aimed to evaluate the effects of Chai-Shi-Jie-Du (CSJD) granules for the treatment of dengue fever and the underlying mechanisms. Methods. We implemented a multicenter real-world study, an in vitro assay and network pharmacology analysis. Patients from 5 hospitals in mainland China who received supportive western treatment in the absence or presence of CSJD were assigned to the control and CSJD groups between 1 August and 31 December 2019. Propensity score matching (PSM) was performed to correct for biases between groups. The clinical data were compared and analyzed. The antidengue virus activity of CSJD was tested in Syrian baby hamster kidney (BHK) cells using the DENV2-NGC strain. Network pharmacological approaches along with active compound screening, target prediction, and GO and KEGG enrichment analyses were used to explore the underlying molecular mechanisms. Results. 137 pairs of patients were successfully matched according to age, sex, and the time from onset to presentation. The time to defervescence (1.7 days vs. 2.5 days, P < 0.05 ) and the disease course (4.1 days vs. 6.1 days, P < 0.05 ) were significantly shorter in the CSJD group than those in the control group. CSJD showed no anti-DENV2-NGC virus activity in BHK cells. Network pharmacology analysis revealed 108 potential therapeutic targets, and the top GO and KEGG terms were related to immunity, oxidative stress response, and the response to lipopolysaccharide. Conclusions. CSJD granules exhibit high potential for the treatment of dengue fever, and the therapeutic mechanisms involved could be related to regulating immunity, moderating the oxidative stress response, and the response to lipopolysaccharide.
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Lin, Jia-Yi, Wei-Wei Zhang, Qing-Jie Li, Xue-Liang Fang, Jun-Yan Li, Shi-Wei He, Ying-Qin Li, et al. "Abstract 1113: USP18 impairs the sensitivity of radiotherapy for nasopharyngeal carcinoma by promoting the ubiquitination and nuclear translocation of TRIM29." Cancer Research 84, no. 6_Supplement (March 22, 2024): 1113. http://dx.doi.org/10.1158/1538-7445.am2024-1113.
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Abstract Radiotherapy is the main and preferred treatment for nasopharyngeal carcinoma (NPC), owing to its high sensitivity to radiation. However, there are ~20% patients suffering from tumor recurrence. Accumulating evidences show that protein ubiquitination plays a vital role in radiation caused DNA damage response. Here, we identified that the deubiquitinase USP18 is highly expressed in NPC tissues, and inversely associated with radiosensitivity of NPC cells. USP18 interacts with TRIM29 and promotes its K27-linked ubiquitination independent of its deubiquitinase activity. Further investigation reveals that USP18 acts as a scaffold to recruit the E3 ubiquitin ligase TRIM21 to directly ubiquitinate TRIM29 at Lys307, thus promoting its oligomerization and nuclear translocation, and thereby facilitates the DNA damage repair of NPC cells after irradiation. Clinically, higher expression of USP18 indicates poor response to radiotherapy and worse prognosis in NPC patients. Our findings reveal the critical role of USP18 in regulating radiosensitivity, and targeting USP18-TRIM21-TRIM29 axis maybe a novel strategy to synergize with radiotherapy for NPC patients. Citation Format: Jia-Yi Lin, Wei-Wei Zhang, Qing-Jie Li, Xue-Liang Fang, Jun-Yan Li, Shi-Wei He, Ying-Qin Li, Jun Ma, Na Liu, Yin Zhao, Rui Guo. USP18 impairs the sensitivity of radiotherapy for nasopharyngeal carcinoma by promoting the ubiquitination and nuclear translocation of TRIM29 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1113.
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Liu, Yuan, Adrian Lankenau-Ahumada, Emine Bayraktar, Paul Schwartz, Mamur Chowdhury, Sixiang Shi, Manu M. Sebastian, et al. "Abstract 2720: Enhancing oral delivery of plant-derived vesicles." Cancer Research 83, no. 7_Supplement (April 4, 2023): 2720. http://dx.doi.org/10.1158/1538-7445.am2023-2720.
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Abstract Plant-derived vesicles (PDVs) were attractive for therapeutic applications, including as potential nanocarriers. However, a concern with oral delivery of PDVs is whether they would remain intact in the gastrointestinal tract. We found that 82% of cabbage PDVs were destroyed under conditions mimicking the upper digestive tract. To overcome this limitation, we developed a delivery method whereby lyophilized Eudragit S-100-coated cabbage PDVs were packaged into a capsule (Cap-cPDVs). Lyophilization and suspension of PDVs in phosphate-buffered saline did not have an appreciable effect on PDV structure, number of PDVs, or therapeutic effect. However, packaging the lyophilized Eudragit S-100-coated PDVs into capsules allowed them to pass through the upper gastrointestinal tract for delivery into the colon better than did suspension of PDVs in phosphate-buffered saline. Cap-cPDVs demonstrated robust therapeutic effect in a dextran sulfate sodium-induced colitis mouse model. These findings could have broad implications for oral delivery of PDVs. Citation Format: Yuan Liu, Adrian Lankenau-Ahumada, Emine Bayraktar, Paul Schwartz, Mamur Chowdhury, Sixiang Shi, Manu M. Sebastian, Htet Khant, Natalia De Val, Zuliang Jie, Nicholas B. Jennings, Cristian Rodriguez-Aguayo, Jody Swain, Elaine Stur, Lingegowda S. Mangala, Yutuan Wu, Supriya Nagaraju, Brooke Erimas, Chun Li, Gabriel Lopez-Berestein, Janet Braam, Anil K. Sood. Enhancing oral delivery of plant-derived vesicles [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2720.
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Yıldırım, Gürol. "Discussion of “Experimental Study on the Multisegment Regime of the Water Flow in Drip Emitters” by Wei Qingsong, Lu Gang, Wang Li, Zheng Jincan, Liu Jie, and Shi Yusheng." Journal of Irrigation and Drainage Engineering 138, no. 12 (December 2012): 1097–100. http://dx.doi.org/10.1061/(asce)ir.1943-4774.0000454.
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Qingsong, Wei, Li Shuai, and Shi Yusheng. "Closure to “Experimental Study on the Multisegment Regime of the Water Flow in Drip Emitters” by Wei Qingsong, Lu Gang, Wang Li, Zheng Jincan, Liu Jie, and Shi Yusheng." Journal of Irrigation and Drainage Engineering 138, no. 12 (December 2012): 1100–1102. http://dx.doi.org/10.1061/(asce)ir.1943-4774.0000494.
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Peng, Li‐hong, Shi‐jie Tang, and Qin Li. "Answer to Letter to the editor: Li‐hong P, Shi‐jie T, Qin L. “Intense pulsed light and laser treatment regimen improves scar evolution after cleft lip repair surgery”." Journal of Cosmetic Dermatology 19, no. 1 (May 11, 2019): 259. http://dx.doi.org/10.1111/jocd.12978.
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Long, Haiping. "On the Formation of Modern Chinese Pseudo-Possessive-Object Constructions." Studies in Language 42, no. 2 (June 6, 2018): 297–328. http://dx.doi.org/10.1075/sl.16018.lon.
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Abstract Modern Chinese Pseudo-Possessive-Object Constructions (shortened as Modern Chinese PPO constructions; e.g. ta shuo le wo de haohua (他说了我的好话) ‘he has put in a good word for me’ and ta chi le wo de doufu (他吃了我的豆腐) ‘he has taken advantage of me’) are actually constructions displaying possessor-affectee syncretism. They derive from Early Modern Chinese Real-Possessive-Object constructions in bridging contexts, some examples being wo ye quande liewei daren de jiu (我也劝得列位大人的酒), ‘I also urged all the magistrates here to finish drinking your wine’ and shi nage zai jie wo de duan li (是那个在揭我的短哩) ‘who is uncovering my demerits’. Di-transitive constructions in Middle Chinese and Early Modern Chinese (e.g. Changxing! quan er yibei jiu (长星，劝尔一杯酒) ‘Comet! I urge you (to finish drinking) a cup of wine’ and shuru gan jie wu duanchu (竖儒敢揭吾短处) ‘how dare the Confucius scholar uncover my demerits’) have provided structural templates for the formation of Modern Chinese PPO constructions. They also have led to a condition in which there are more examples of a maleficiary Modern Chinese PPO construction than examples of a beneficiary Modern Chinese PPO construction (e.g. ta chi le wo de doufu (他吃了我的豆腐) ‘he has taken advantage of me’ vs. ta shuo le wo de haohua (他说了我的好话) ‘he has put in a good word for me’). The grammaticalization pathway can also explain the formation of other constructions including another Modern Chinese PPO construction (e.g. ta chi le wo de kui (他吃了我的亏) ‘he has suffered the loss caused by me’), a Modern Chinese pseudo-object construction (e.g. wo ganxie ni de haoxin (我感谢你的好心) ‘I thank you for your kindness’), and a Modern Chinese pseudo-modifier construction (e.g. wo pa le yi xiawu de shan (我爬了一下午的山) ‘I did mountain-climbing for the whole afternoon’).
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Peng, PeiJian, Xiao-Lu Xu, Jin-Cai Zhong, Jin-Hui Ye, Zhi-Hui Wang, Hong Wang, Hong Lin, et al. "Abstract PO3-05-10: Efficacy and safety of eribulin plus gemcitabine in second-line or beyond for patients with HER2-negative metastatic breast cancer (MBC): A multi-center, open-label, single-arm, phase II study." Cancer Research 84, no. 9_Supplement (May 2, 2024): PO3–05–10—PO3–05–10. http://dx.doi.org/10.1158/1538-7445.sabcs23-po3-05-10.
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Abstract Background: Eribulin is a halichondrin non-taxane inhibitor of microtubule dynamics approved in China for advanced breast cancer patients who have received at least two prior chemotherapy treatments. The combination of eribulin and gemcitabine has demonstrated a similar progression-free survival (PFS) benefit as paclitaxel plus gemcitabine, with less neurotoxicity, for patients with MBC who have not received prior cytotoxic chemotherapy. However, the effect of eribulin plus gemcitabine on PFS in second line or beyond remains unclear. Methods: This open-label, single-arm, phase II study (NCT05263882) was conducted at 13 institutions in China. Eligible patients had histologically confirmed HER2-negative MBC and had received at least one prior taxane-containing chemotherapy regimen for advanced disease, and anthracycline-containing regimens in the adjuvant setting. Patients received intravenous infusions of eribulin (1.4 mg/m2) and gemcitabine (1.0 g/m2) on days 1 and 8 of a 21-day cycle. Efficacy outcomes, including PFS, objective response rate (ORR), and disease control rate (DCR), were assessed using RECIST v1.1. Adverse events (AEs) were graded according to NCI-CTC version 5.0. Results: A total of 65 patients were enrolled from November 2021 to May 2023; 47 (72.3%) had HR+/HER2- and 18 (27.7%) had triple-negative MBC. The median patient age was 50 years (range: 31-68), and the sites of metastasis were the bone (70.8%), liver (58.5%), lymph nodes (50.8%), lung (43.1%) and brain (10.8%). Patients had received a median of 3 prior lines of systemic treatment, 2 lines of chemotherapy, and 1 line of endocrine treatment. Among all patients, the ORR was 52.3%, the DCR was 92.3% and the median PFS was 7.6 months (Table). For the HR-positive subgroup, the median PFS was 8.4 months, while for the triple-negative subgroup, it was 7.6 months. Among patients who had received prior CDK4/6 inhibitor treatment, the median PFS was 7.2 months. In the subgroup of patients who had not received CDK4/6 inhibitor treatment, the median PFS had not been reached. The most common grade 3-4 AEs were hematological, including neutropenia (41.6%), leukopenia (33.9%), anemia (23.1%), and thrombocytopenia (15.4%). No grade ≥3 perceived AEs were reported. Conclusion: Eribulin plus gemcitabine was effective in heavily pretreated patients with HER2- MBC, while maintaining a predictable and manageable safety profile. Table. Summary of efficacy outcomes Citation Format: PeiJian Peng, Xiao-Lu Xu, Jin-Cai Zhong, Jin-Hui Ye, Zhi-Hui Wang, Hong Wang, Hong Lin, Cai-Wen Du, Guorong Zou, Jie Ouyang, Ying-Ying Shi, Fei Xu, Geng-Sheng Yu, Yong-Kui Lu, Yong-Xia Wang, Shi-En Cui, Lu-Zhen Li. Efficacy and safety of eribulin plus gemcitabine in second-line or beyond for patients with HER2-negative metastatic breast cancer (MBC): A multi-center, open-label, single-arm, phase II study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-05-10.
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Ou, Yang, Kun Zhang, Qiuying Shuai, Chenyang Wang, Huayu Hu, Lixia Cao, Chunchun Qi, et al. "Abstract 4556: USP51-GRP78-ABCB1 axis promotes chemoresistance of triple negative breast cancer by decreasing the accumulation of doxorubicin in cells." Cancer Research 84, no. 6_Supplement (March 22, 2024): 4556. http://dx.doi.org/10.1158/1538-7445.am2024-4556.
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Abstract Background: Resistance to chemotherapy remains an obstacle for triple-negative breast cancer (TNBC) patients. The core components of the ubiquitin-proteasome system have been demonstrated to regulate chemoresistance of TNBC. As a novel deubiquitinase (DUB), ubiquitin-specific peptidase 51 (USP51) plays a pivotal role in chemotherapeutic resistance in multiple malignancies. Herein, we sought to better understand how USP51 performs a cell-intrinsic role in mediating chemotherapeutic resistance in TNBC. Methods: Western blotting, RNA-sequencing and CCK8 assays were used to identify the DUBs for chemoresistance of breast cancer. Coimmunoprecipitation, GST-pulldown, protein deubiquitination and immunohistochemistry assays were then used to determine the biological phenotypes of ectopic USP51 in TNBC chemoresistance and associated signaling pathways in several different cell lines, mouse models and patient tissue samples. Ubiquitin-7-amido-4-methylcoumarin (Ub-AMC)-based deubiquitinase activity, cellular thermal shift and surface plasmon resonance (SPR) analyses were performed to investigate the activity of USP51 inhibitors. Results: To identify the critical DUBs involved in breast cancer chemoresistance, we established doxorubicin-resistant Cal51 and MDA-MB-231 TNBC cell lines by multiple dose exposure. We found ectopic USP51 in doxorubicin-resistant cells compared with their parental cells. Moreover, USP51-interfered chemoresistant tumor cells exhibited impaired cell viability as well as increased DNA damage and cell apoptosis upon treatment with doxorubicin. On the contrary, overexpression of USP51 performed the opposite effects to enhance cell viability but decrease DNA damage and apoptosis in response to doxorubicin; however, these outcomes were not shown for its catalytically inactive mutant USP51C372S. At the molecular level, GRP78 was identified as a bona fide substrate of USP51. Importantly, knockdown USP51 increased doxorubicin-induced DNA damage and apoptosis, which was rescued by overexpression of GRP78 in vitro and in vivo. In addition, the activity of ABCB1, the main efflux pump of doxorubicin, was enhanced by GRP78. Consistently, the expression of USP51, GRP78 and ABCB1 were correlated with chemoresistant phenotypes in TNBC patients. Of note, we also explored a small molecular inhibitor of USP51, WCY-4-1, which conferred chemosensitization in TNBC. Conclusion: These findings collectively indicated that ectopic USP51 enhances the activity of ABCB1 by deubiquitinating and stabilizing GRP78, which leads to decreased accumulation of doxorubicin as well as decreased DNA damage and cell apoptosis in TNBC. Our results also revealed that specific inhibition of USP51 significantly impairs doxorubicin-resistance in TNBC. Citation Format: Yang Ou, Kun Zhang, Qiuying Shuai, Chenyang Wang, Huayu Hu, Lixia Cao, Chunchun Qi, Min Guo, Zhaoxian Li, Jie Shi, Yuxin Liu, Siyu Zuo, Xiao Chen, Yanjing Wang, Mengdan Feng, Hang Wang, Yi Shi, Guang Yang, Shuang Yang. USP51-GRP78-ABCB1 axis promotes chemoresistance of triple negative breast cancer by decreasing the accumulation of doxorubicin in cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4556.
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Komisarek, Oskar, Patrycja Bartkowska, and Teresa Matthews‐Brzozowska. "Li‐hong P, Shi‐jie T, Qin L. Intense pulsed light and laser treatment regimen improves scar evolution after cleft lip repair surgery. J Cosmet Dermatol. 2018;1‐4. https://doi.org/10.1111/jocd.12684." Journal of Cosmetic Dermatology 18, no. 6 (April 25, 2019): 2050. http://dx.doi.org/10.1111/jocd.12956.
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Shi, JiaJie, Wei Li, Zhongsheng Tong, Aimin Zang, Xiaohua Zeng, Shui Wang, Tao Huang, et al. "Abstract P4-01-21: Phase 2 Study of the CDK4/6 Inhibitor FCN-437c in Combination With Fulvestrant or Letrozole and Goserelin in Patients With HR+, HER2– Advanced Breast Cancer." Cancer Research 83, no. 5_Supplement (March 1, 2023): P4–01–21—P4–01–21. http://dx.doi.org/10.1158/1538-7445.sabcs22-p4-01-21.
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Abstract Background: FCN-437c is a second-generation CDK4/6 inhibitor. Phase 1b clinical results indicated improved antitumor activity in patients (pts) with HR+, HER2– advanced breast cancer (ABC), treated with FCN-437c + letrozole. Methods: This Phase 2, multicenter, open-label clinical study evaluated the antitumor activity, pharmacokinetics (PK), and safety of FCN-437c + fulvestrant in post-menopausal pts (Cohort 1, treatment-naïve or 2L), FCN-437c + letrozole + goserelin in pre-menopausal pts (Cohort 2, treatment-naïve). Pts received FCN-437c (200 mg QD) in a 21-day-on and 7-day-off schedule either in combination with fulvestrant (500 mg D1) or letrozole (2.5 mg QD) + goserelin (3.6 mg once per cycle) in 28-day cycles. The primary endpoint was overall response rate (ORR) and secondary endpoints were progression-free survival (PFS), overall survival (OS), PK, and safety. Results: At study cutoff (Feb 7, 2022), 36 pts were enrolled in Cohort 1 and 31 pts were in Cohort 2; 42 (62.7%) pts had visceral metastases and 9 (13.4%) pts had bone-only metastases. In Cohort 1, 18 pts were treatment-naïve, 15 pts had received 1L treatment, and 3 pts had received ≥2L treatment. In Cohort 2, 25 pts were treatment-naïve and 6 pts had received 1L treatment. Overall, 27 pts in the per-protocol set achieved partial response (PR), resulting in an ORR of 40.9% (95% CI, 29.0-53.7). Median follow-up was 12.8 months, and median PFS (mPFS), OS, and DOR were not reached. However, at 12 months, the PFS rate was 67.7% (95% CI, 53.2-78.6) and the OS rate was 95.9% (95% CI, 84.5-99.0); the 6-month DOR rate was 96.0% (95% CI, 74.8-99.4). In Cohort 1 (n=35), 11 pts achieved PR: the ORR was 31.4% (16.9-49.3%) and mPFS was 12.9 months (95% CI, 9.2-NR); the 6-month DOR rate was 100%. In Cohort 2 (n=31), 16 pts achieved PR: the ORR was 51.6% (95% CI, 33.1-69.9%). mPFS, OS, and DOR were not reached; the 6-month DOR rate was 92.9% (95% CI, 59.08-98.96) (Table). Treatment-emergent adverse events (TEAEs) were observed in all pts. Majority of AE were G1 or 2 except for hematological TEAE. 58 (86.6%) pts reported grade ≥3 TEAEs, mainly neutropenia (74.6%), leukopenia (49.3%), hypertriglyceridemia (6.0%), lymphocyte count decrease (4.5%), and γ-glutamyltransferase increase (3.0%): most were reversed through dose interruption and symptomatic therapy. Steady-state PK parameters were analyzed after 15-21 days of QD administration: Cohort 1: median Tmax was 3 h, geomean T1/2 was 44.6 h, geomean Cmax was 1650.7 ng/mL, and geomean AUC0-24h was 29,148.08 h*ng/mL; the geomean accumulation ratios of AUC0-24h and RCmax were 2.18 and 1.74, respectively, compared with first dose. Cohort 2: median Tmax was 4 h, geomean T1/2 was 35.7 h, geomean Cmax was 1314.34 ng/mL, and geomean AUC0-24h was 22,889.96 h*ng/mL; the geomean accumulation ratios of AUC0-24h and RCmax were 1.95 and 1.63, respectively, compared with first dose. Conclusion: FCN-437c in combination with fulvestrant or letrozole + goserelin demonstrates antitumor activity and safety and is well tolerated in pts with HR+, HER2– ABC. This combination therapy will be further investigated in 2 ongoing Phase 3 trials (NCT05438810 and NCT05439499). Clinical trial number: NCT05004142. Research Sponsor: Avanc Pharmaceutical Co., Ltd Table. Clinical outcomes for patients in the per-protocol set. Citation Format: JiaJie Shi, Wei Li, Zhongsheng Tong, Aimin Zang, Xiaohua Zeng, Shui Wang, Tao Huang, Ying Wang, Yanqiu Song, Lihua Kang, Zheng Lv, Yehui Shi, Hua Yang, Jing Wu, Yongmei Yin, Yan Liang, Jie Tan, Jie Ming, Yaping Yang, Simin Luo, Xiujuan Gui, Ai-Min Hui, Zhuli Wu, Ling Tian, Yuchen Yang, Lei Diao, Wenjing Zhang, Yongjiao Zhang, Yunjiang Liu. Phase 2 Study of the CDK4/6 Inhibitor FCN-437c in Combination With Fulvestrant or Letrozole and Goserelin in Patients With HR+, HER2– Advanced Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-21.
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Zhang, Nannan, Bin Shen, Shenyan Liu, Cheng Dai, Haiyan Ying, Fushen Guo, Zhixuan Zhu, et al. "Abstract LB077: CSF-1R inhibition with Pimicotinib (ABSK021) enhanced anti-tumor efficacy of KRASG12C inhibitors in preclinical non-small cell lung cancer mouse models." Cancer Research 84, no. 7_Supplement (April 5, 2024): LB077. http://dx.doi.org/10.1158/1538-7445.am2024-lb077.
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Abstract Background: KRAS mutations are highly prevalent oncogenic drivers in human cancers and KRASG12C is the most frequent mutations found in KRAS-mutant non-small lung cancer (NSCLC). It is reported that tumor associated macrophages (TAMs) are enriched in KRAS-driven transgenic lung cancer models. Depletion of macrophage results in a significant decrease in tumor burden and increased survival. Sotorasib (AMG510), the first KRASG12C inhibitor approved by FDA, has been found to modulate tumor immunity, impacting the recruitment of macrophages. CSF-1R signaling is critical for macrophage proliferation and survival. CSF-1R inhibition depletes TAMs and reprograms tumor microenvironment (TME), resulting in enhancement of anti-tumor immunity. Therefore, the combination of KRASG12C and CSF-1R inhibitors may synergize to enhance anti-tumor efficacy. Pimicotinib (ABSK021) is a potential best-in-class small molecule inhibitor of CSF-1R in clinical development of multiple indications. Here, we conducted in vivo experiments to explore the combined effects of KRASG12C and CSF-1R inhibitors. Methods: In vivo efficacy studies were performed to evaluate the combined treatment of KRASG12C inhibitors (AMG510 and ABSK071, a next-generation inhibitor targeting KRASG12C with better inhibitory activity) and CSF-1R inhibitor (ABSK021) in NCI-H2122 PBMC humanized mice and LLC syngeneic mice. RNA sequencing was employed to investigate the mechanism of action underlying the synergistic anti-tumor effect. Immunohistochemistry (IHC) was utilized to examine the changes of immune cell populations in TME. Results: The combinatory regimen of ABSK021 and KRASG12C inhibitors showed improved anti-tumor effects than each single agent alone in both mouse NSCLC models. Bioinformatics and follow-up analysis revealed a reduction in immune suppressive TAMs in tumors treated with ABSK021 alone or in combination with KRASG12C inhibitors. Furthermore, modulation of TME related to anti-tumor immunity, such as activated CD4 T, CD8 T and NK cells, was increased, and pro-tumor immunity, such as MDSC, regulatory T cells, was decreased in combination group. IHC results confirmed that ABSK021 addition led to macrophage depletion and more CD8 T cell infiltration in TME. Conclusions: For the first time, we demonstrate that the combined inhibition of KRASG12C and CSF-1R leads to superior therapeutic efficacy in preclinical NSCLC mouse models. This results suggests a potential novel therapeutic regimen that could yield improved clinical benefit to patients. Citation Format: Nannan Zhang, Bin Shen, Shenyan Liu, Cheng Dai, Haiyan Ying, Fushen Guo, Zhixuan Zhu, Wan Shi, Min Tu, Jie Wang, Jie Zhang, Manqi Liu, Qi Zhang, Zhui Chen. CSF-1R inhibition with Pimicotinib (ABSK021) enhanced anti-tumor efficacy of KRASG12C inhibitors in preclinical non-small cell lung cancer mouse models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB077.
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Liu, Beibei, an Li, Xiangyang Zuo, Jie Yang, Ruifeng Wang, Feifei Fan, Wenting Shi, and Qingyang Gu. "Abstract 4984: Integrated platform enables KRAS-targeted drugs discovery." Cancer Research 83, no. 7_Supplement (April 4, 2023): 4984. http://dx.doi.org/10.1158/1538-7445.am2023-4984.
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Abstract The Kirsten rat sarcoma viral oncogene homolog (KRAS) is mutated in approximately 25% of all human cancers and is known to be a major player promoting and maintaining tumorigenesis through the RAS-MAPK pathway. Activating mutations in KRAS increase the ability for GTP-loading, making it difficult to displace, thus constitutively activate downstream MAPK pathway and promote cancer formation. Fortunately, a revolutionary strategy to use covalent allosteric inhibitors that target a shallow pocket on the KRAS surface has provided new impetus for KRAS inhibitor development efforts. These inhibitors, such as AMG510 and MRTX849, show promising results in patients with tumors harboring KRAS G12C mutation. While the approval of AMG510 was a major breakthrough for those patients harboring KRAS G12C mutations, G12C only accounts for a fraction of those with KRAS mutations and eventual resistance to G12C inhibitors is unavoidable. Therefore, develop new drugs direct various KRAS mutants and combination strategies that target resistance mechanisms have become vital in the war against KRAS-mutant tumors. To enable the discovery of novel KRAS inhibitors, we established a one-stop service platform, covering affinity detection of compounds to KRAS mutants, KRAS upstream and downstream protein-protein interaction detection, pathway activation detection, cell proliferation assay (2D/3D culture system), and in vivo efficacy evaluation in KRAS mutant xenograft models. Our platform provides assays on nearly all the current mainstream mutants of KRAS, such as G12C/G12D/G12R/G12S/G13D, and engineered Ba/F3 cell lines that harboring single or double KRAS mutation. In addition, we developed a panel of resistant models to KRAS G12C inhibitor that bringing a better understanding of the biological basis of drug resistance, and will serve as a new tool to optimize KRAS-G12C inhibitor regimens and combinatorial strategies. The comprehensive KRAS-targeted drug discovery platform is empowering new drug research and development. Citation Format: Beibei Liu, an Li, Xiangyang Zuo, Jie Yang, Ruifeng Wang, Feifei Fan, Wenting Shi, Qingyang Gu. Integrated platform enables KRAS-targeted drugs discovery. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4984.
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Lin, Yanan, Shengbang Zhang, Jie Ran, Can Song, Shengcang Zhu, Hui Shi, Ping Guo, Shengjiang Tan, Yuchun Gu, and Lida Wu. "Abstract 5135: Standardized off-the-shelf engineered NK cell therapy with improved ADCC properties to treat malignancies." Cancer Research 83, no. 7_Supplement (April 4, 2023): 5135. http://dx.doi.org/10.1158/1538-7445.am2023-5135.
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Abstract In the treatment of solid tumors, chimeric antigen receptor(CAR)-engineered NK (CAR-NK) cells have distinct advantages over CAR-T cells, such as a lack graft-versus-host disease in allogenic setting to make “off the shelf” medicine; much safer because they are less likely to cause cytokine storms; and NK cells have their own activated receptors that recognize tumor surface antigens and thus have a natural ability to kill a wide range of tumors. In addition, NK cells are the main performers of antibody-dependent cell-mediated cytotoxicity (ADCC), which binds to the Fc-terminus of antibodies through their surface Fc receptor CD16A, thereby killing antibody-targeted tumor cells. Enhancing the ADCC action of NK cells themselves enhances the therapeutic efficacy of monoclonal antibodies targeting tumor surface antigens and is therefore of great importance in the treatment of tumors, especially solid tumors. We screened two optimal structures among nine different Fc chimeric receptors, and NK cells overexpressing these two receptors killed K562 and Daudi six times more intensely than normal NK cells when combined with rituximab, while the killing ability was comparable to that of normal NK without rituximab, indicating that NK cells expressing chimeric Fc receptors have stronger ADCC effects. Moreover, these NK cells can kill target cells in multiple rounds. In vivo experiments in mice demonstrated that NK cells expressing chimeric Fc receptors in combination with EGFR monoclonal antibodies had a stronger inhibitory effect on tumor growth than monoclonal antibodies or NK cells alone. Here we provide a novel broad “off the shelf” NK cells that can significantly enhance the killing ability of hematological and solid tumors in combination with different monoclonal antibodies. Citation Format: Yanan Lin, Shengbang Zhang, Jie Ran, Can Song, Shengcang Zhu, Hui Shi, Ping Guo, Shengjiang Tan, Yuchun Gu, Lida Wu. Standardized off-the-shelf engineered NK cell therapy with improved ADCC properties to treat malignancies. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5135.
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Shi, Hui, Yanan Lin, Jie Ran, Yan Jin, Shengbang Zhang, Qi Wang, Huiyuan Zhang, et al. "Abstract CT099: First-in-human study of ALF501, polypeptide PSMA-targeted chimeric antigen receptor engineered natural killer cells) for castration-resistant prostate cancer." Cancer Research 83, no. 8_Supplement (April 14, 2023): CT099. http://dx.doi.org/10.1158/1538-7445.am2023-ct099.
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Abstract Abstract Background: The mortality of castration-resistant prostate cancer (CRPC) is high due to lack of an effective treatment. Chimeric antigen receptor (CAR) based therapy is a promising immunotherapeutic strategy. In preclinical models, we established ALF501, a novel CAR-NK cells with both a high affinity for PSMA and a clinically significant tumoricidal effect on CRPC. Here we report the results from the first-in-human case of ALF501 for CRPC. Methods: In this study, ALF501was dosed intravenous for a total of three courses, with an interval of 3 months, each infusion of 5 × 108 cells, and 3 consecutive days of infusion as a course of treatment. Observation continued until progression or unacceptable toxicity for up to 1 years. Primary objectives were safety and tolerability; secondary objectives included preliminary antitumor activity. Results: An 80-year-old man who underwent laparoscopic radical prostatectomy in February 2018 and developed a relapse in April 2021. Starting with July 16 2021, he received three courses of ALF501. No liver and kidney toxicity was observed, and the safety profile was good. Progression-free survival was 12months as of April 23, 2022, during which PSA decreased by 97.5% from baseline. Imaging follow-up showed that the tumor was stable, and chest CT showed that the original pleural effusion and pericardial effusion disappeared, and the high-density shadow previously considered osteogenic bone metastasis was reduced overall. Conclusions: ALF501 is safe and feasible for the treatment of CRPC, and has preliminary anti-tumor efficacy. This is a case study, and it is necessary to expand the patient sample size in the future to confirm whether there is a difference in efficacy for different patients. Citation Format: Hui Shi, Yanan Lin, Jie Ran, Yan Jin, Shengbang Zhang, Qi Wang, Huiyuan Zhang, Lida Wu, Yuchun Gu, Shengjiang Tan, Yao Wang. First-in-human study of ALF501, polypeptide PSMA-targeted chimeric antigen receptor engineered natural killer cells) for castration-resistant prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT099.
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Na, Min Gu, and SooBin Lee. "An Analysis of Meanings and Sociolinguistic Features Shown in 說文解字今釋Shuo wen jie zi jin shi “口部字kou buzi” and 現代漢語大詞典The Contemporary Chinese Dictionary." Korea Journal of Chinese Linguistics 74 (February 28, 2018): 343–70. http://dx.doi.org/10.38068/kjcl.74.14.
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Iskatriati, Lidia, Lily Thamrin, and Suhardi Suhardi. "ANALISIS PENGUASAAN SUFIKS MANDARIN “JIA, YUAN, SHI, SHOU, ZHE” PADA MAHASISWA PRODI PENDIDIKAN BAHASA MANDARIN." CaLLs (Journal of Culture, Arts, Literature, and Linguistics) 8, no. 1 (June 30, 2022): 59. http://dx.doi.org/10.30872/calls.v8i1.7044.
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Sufiks adalah imbuhan yang diletakkan dibelakang akar kata atau kata dasar. Sufiks mandarin “Jia, Yuan, Shi, Shou, Zhe” merupakan imbuhan tanda kata benda yang menunjuk pada seseorang. Setiap kosa kata yang termasuk dalam imbuhan ini memiliki arti, namun tidak semua memiliki arti yang sama, sehingga tidak dapat digunakan bergantian.Tujuan dari penelitian ini adalah untuk mengetahui kondisi penguasaan dan kesulitan Mahasiswa Angkatan 2018 Prodi Pendidikan Bahasa Mandarin FKIP UNTAN terhadap Sufiks Mandarin “Jia, Yuan, Shi, Shou, Zhe”. Penelitian ini adalah penelitian kualitatif dengan metode analisis deskriptif kualitatif dengan menggunakan pengumpulan data soal tes. Hasil penelitian menyatakan, bahwa penguasaan Mahasiswa pada Sufiks “Jia” lebih baik dari pada Sufiks “Yuan, Shi, Shou, Zhe”. Presentase jawaban benar pada Sufiks “Jia” mencapai 55,47%, sedangkan Sufiks “Yuan” 39,06%, Sufiks “shi” 47,66%, Sufiks “Shou” 39,84% dan Sufiks “Zhe” 38,28%. Dalam analisis kesulitan, penulis menyadari bahwa Mahasiswa kurang menguasai pada Sufiks “Jia” menunjuk orang yang termasuk dalam kelas tertentu, pada Sufiks “yuan” menunjuk orang yang terlibat dalam profesi atau pekerjaan tertentu, pada Sufiks “Shi” menunjukkan panggilan nama yang baik untuk seseorang, pada Sufiks “Shou” menunjuk orang yang melakukan aktivitas dan tindakan tertentu, dan pada Sufiks “Zhe” menunjuk orang dengan sifat dan karakteristik tertentu
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김예신. "Zuo-zhuan(左傳) School’s View of Nature and Zai-yi(災異) Theory During the Later Han Dynasty: Focusing on Chun-qiu Zuo-shi Zhuan Jie-yi(春秋左氏傳解誼) Written by Fu-qian(服虔)." Historical Studies of Ancient and Medieval China ll, no. 37 (August 2015): 151–95. http://dx.doi.org/10.15840/amch.2015..37.005.
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Kühn, Sebastian Paul, Dominik Weintz, Martin Winter, and Isidora Cekic-Laskovic. "The SEI on Lithium Metal Anodes: From Understanding to Enhancement." ECS Meeting Abstracts MA2022-02, no. 4 (October 9, 2022): 373. http://dx.doi.org/10.1149/ma2022-024373mtgabs.
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Lithium metal batteries (LMB) have risen back into focus of battery research in resent years, due to the high theoretical specific capacity of the lithium metal anodes (3860 mAh g-1).[1] However, the utilization of lithium metal as an anode material requires an in depth understanding of the solid electrolyte interphase (SEI) on lithium metal electrodes, since its formation, composition and electrochemical characteristics significantly impact important LMB lifetime parameters, e.g. lithium stripping/plating behaviour, dendrite growth and in operando electrolyte consumption.[2] Lithium metal electrode performance is influenced by a variety of different, however often overlooked factors, e.g. the native passivation layer, inevitably present on each lithium metal electrode surface, which has only recently gathered more attention as an influencing factor in respect to SEI characteristics.[3] The presented research utilizes the preformation of an uncontaminated SEI on the lithium metal electrode surface to circumvent the influence of native lithium metal passivation. A systematic study of different preformed SEIs resulted in a better understanding of the influence by different electrolyte components on relevant SEI characteristics, namely, selected conducting salts (LiFSI, LiPF6) and functional additives (VC, FEC). Analyses of the SEIs electrochemical properties, composition, morphology and dynamics were conducted via stripping/plating experiments as well as in operando EIS, SEM (incl. cryogenic cross section and post mortem) and XPS (post mortem) measurements. Finally, careful tailoring of the preformed SEI was shown to have an enhancing effect on NMC811||Li cells, increasing the LMB lifetime by up to 25%. Furthermore, the application of a tailored preformed SEI has also shown a positive impact on the performance of solid state LMBs. The presented results highlight the importance of an in depth understanding regarding the cause and effect of varying electrolyte components on the SEIs characteristics. This understanding will ultimately have a significant impact on the research towards enhanced and reliable LMB performance and future applicability. References: [1] D. Jin, J. Park, M. H. Ryou, Y. M. Lee, Adv. Mater. Interfaces 2020, 7, 1–17. [2] B. Horstmann, J. Shi, R. Amine, M. Werres, X. He, H. Jia, F. Hausen, I. Cekic-Laskovic, S. Wiemers-Meyer, J. Lopez, D. Galvez-Aranda, F. Baakes, D. Bresser, C.-C. Su, Y. Xu, W. Xu, P. Jakes, R.-A. Eichel, E. Figgemeier, U. Krewer, J. M. Seminario, P. B. Balbuena, C. Wang, S. Passerini, Y. Shao-Horn, M. Winter, K. Amine, R. Kostecki, A. Latz, Energy Environ. Sci. 2021, 14, 5289–5314. [3] S. Otto, T. Fuchs, Y. Moryson, C. Lerch, B. Mogwitz, J. Sann, J. Janek, A. Henss, Appl. Energy Mater. 2021, 4, 12798–12807.
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Chen, Jie-yao, Shi-jun Chen, Wei-bin Huang, and Guang-wen Ma. "Erratum for “Discussion of ‘New Flood Early Warning and Forecasting Method Based on Similarity Theory’ by Zhangling Xiao, Zhongmin Liang, Binquan Li, Bo Hou, Yiming Hu, and Jun Wang” by Jie-yao Chen, Shi-jun Chen, Wei-bin Huang, and Guang-wen Ma." Journal of Hydrologic Engineering 26, no. 1 (January 2021): 08220003. http://dx.doi.org/10.1061/(asce)he.1943-5584.0002024.
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Zhu, Bing, Shi-Li Yao, Xin-Yan Wang, Rui Xu, Peng Guo, and Jie-Er Ying. "Abstract 6175: Developing antibody-drug conjugates against cholangiocarcinoma using a novel molecular target." Cancer Research 82, no. 12_Supplement (June 15, 2022): 6175. http://dx.doi.org/10.1158/1538-7445.am2022-6175.
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Abstract As a rare malignancy, cholangiocarcinoma (CCA) is a lethal disease with a 5-year overall survival rate of merely 5%. Highly invasive and asymptomatic characteristics of CCA cause most patients diagnosed at advanced stages, severely deteriorating their clinical outcomes. The drug treatment options for CCA are limited and surgical resection of CCA frequently suffers from a high recurrence rate of 66%. Albeit Pemigatinib, a FGFR2 inhibitor, has recently been approved by FDA as the first CCA-targeted therapeutic, only less than 10% of patients with CCA carry FGFR2 fusion mutations that can benefit from this drug. Ivosidenib, another targeted drug against IDH1 mutation, only works for 13% CCA patients carrying this mutation. Therefore, discovering new molecular targets and developing associated targeted drugs remain a significant and unmet medical need in CCA therapy. In this study, we first screened potential molecular targets for CCA by comparing the expression levels of a panel of cancer-related cell membrane antigens between human CCA cells and normal human intrahepatic biliary epithelial cells through flow cytometry. CD54 was identified as a remarkable molecular target of CCA with strong binding force to its antibodies and high endocytosis efficiency by flow cytometry and confocal fluorescent microscopy. Meanwhile, we confirmed that CD54 was absent in most normal human tissues but was highly upregulated in CCA tumor tissues through immunohistochemical (IHC) staining. Based on this newly discovered CCA target, we constructed a series of CD54 antibody-drug conjugates (ADCs) using different chemical linkers and payloads. We next evaluated and compared the half maximum inhibitory concentrations (IC50s) of each ADC in ablating human CCA cells in vitro in order to identify an optimized ADC formulation. Furthermore, we validated its anti-tumor efficacy against primary and peritoneal metastatic CCA tumors in vivo in comparison with conventional chemotherapy. Eventually, we determined the biodistribution and safety profile of this CD54 ADC in order to ensure that it is well-tolerated under the effective dose. In general, we identified CD54 as a novel molecular target for CCA through antibody library screening, and explored its potential in the development of CCA-targeted ADCs, providing a promising targeted therapeutic for clinical treatment of CCA. Citation Format: Bing Zhu, Shi-Li Yao, Xin-Yan Wang, Rui Xu, Peng Guo, Jie-Er Ying. Developing antibody-drug conjugates against cholangiocarcinoma using a novel molecular target [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6175.
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Amirghofran, Ahmadali, Mohammadreza Edraki, Elahe Nirooei, and Abbas Emaminia. "Reply to Hosseinpour et al. and Jia and Shi." European Journal of Cardio-Thoracic Surgery 60, no. 2 (February 18, 2021): 439. http://dx.doi.org/10.1093/ejcts/ezab074.
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Hamilton, Erika, Jian Zhang, Liming Liu, Jie Gao, Rong Shi, Shengxue Liu, Gu Wei, Yang Qiu, and Kathleen Moore. "Abstract CT247: A Phase 1/2a, multicenter, open-label, non-randomized first-in-human study to assess the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of DB-1303 in patients with advanced/metastatic solid tumors." Cancer Research 83, no. 8_Supplement (April 14, 2023): CT247. http://dx.doi.org/10.1158/1538-7445.am2023-ct247.
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Abstract Background: Epidermal growth factor receptor 2 (EGFR2 or HER2) has shown gene amplification/over-expression in more than 30% of all human cancers, including breast cancer, gastric, colon, salivary gland, bladder, and uterine serous carcinoma, and its overexpression in tumors is associated with poor prognosis. DB-1303 (developed by DUALITYBIO INC.) is an antibody-drug conjugate (ADC) comprised of a humanized anti-HER2 IgG1 monoclonal antibody (BAT0606), covalently linked to a proprietary DNA topoisomerase I inhibitor (P1003) via a cleavable linker containing maleimide tetrapeptide (GGFG), with a drug-to-antibody ratio (DAR) of approximately 8. Preclinical studies demonstrated a favorable safety profile and a potent antitumor activity of DB-1303 compared with approved HER2-ADC. These studies warrant further clinical development of the study drug. Methods: This is a global first-in-human Phase 1/2a study (NCT05150691) to assess the safety, tolerability, and anti-tumor activities of the study drug DB-1303 in patients with pretreated advanced/metastatic solid tumors. Patients should have histologically confirmed HER2-positive or HER2-expressing cancers who failed previously systemic therapies, ECOG 0-1, and adequate organ function. The dose escalation part will evaluate seven ascending dose levels of DB-1303 (accelerated titration design for the first dose level and “3+3” design for the rest dose levels) to determine recommended phase 2 dose (RP2D) or maximum tolerated dose (MTD). The study drug will be administrated iv infusion Q3W, and dose-limiting toxicity (DLT) will be assessed during Cycle 1 (1st 3 weeks). Phase 2a part will initiate after MTD and/or RP2D are determined. Phase 2a part only enrolls the patients with HER2-positive gastric, esophageal, or gastroesophageal junction adenocarcinoma, colorectal cancers, HER2 overexpression and HER2-low endometrial carcinoma, hormone receptor-positive (HR+)/HER2-low breast cancer, HER2-positive breast cancer, and activating HER2-mutated NSCLC. The study treatment of DB-1303 will continue until disease progression, withdrawal of consent, or unacceptable toxicity. Tumor responses will be assessed every 6-9 weeks with RECIST v1.1. The study planned to enroll 253 patients from sites in the United States, Australia, and China (88 patients in Phase I and 165 patients in Phase 2a). Citation Format: Erika Hamilton, Jian Zhang, Liming Liu, Jie Gao, Rong Shi, Shengxue Liu, Gu Wei, Yang Qiu, Kathleen Moore. A Phase 1/2a, multicenter, open-label, non-randomized first-in-human study to assess the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of DB-1303 in patients with advanced/metastatic solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT247.
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Gao, Yue, Chun-Jie Liu, Hua-Yi Li, Xiao-Ming Xiong, Sjors G. j. g. In ‘t Veld, Gui-Ling Li, Jia-Hao Liu, et al. "Abstract LB168: Platelet RNA signature enables early and accurate detection of ovarian cancer: An intercontinental, biomarker identification study." Cancer Research 82, no. 12_Supplement (June 15, 2022): LB168. http://dx.doi.org/10.1158/1538-7445.am2022-lb168.
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Abstract Background: Morpho-physiological alternations of platelets provided a rationale to harness RNA sequencing of tumor-educated platelets (TEPs) for preoperative diagnosis of cancer. Timely, accurate, and non-invasive detection of ovarian cancer in women with adnexal masses presents a significant clinical challenge. Patients and Methods: This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n=3; Netherlands, n=5; Poland, n=1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. Results: The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. Analysis of public datasets suggested that TEPs had potential to detect multiple malignancies (Table 1). Conclusions: TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, early-stage ovarian cancer as well as other malignancies. However, these observations warrant prospective validations in a larger population before clinical utilities. Table 1. Performance for TEPs in public pan-cancer datasets. Disease n Healthy Control AUC, area under the curve (95% CI) Women NSCLC (non-small-cell lung cancer) 126 77 0.758 (0.691-0.825) Breast cancer 38 77 0.817 (0.726-0.909) Colorectal cancer 18 77 0.973 (0.945-1.000) Pancreatic cancer 16 77 0.993 (0.981-1.000) Glioblastoma 10 77 0.923 (0.831-1.000) Men NSCLC 119 82 0.746 (0.677-0.815) Colorectal cancer 25 82 0.933 (0.884-0.982) Pancreatic cancer 22 82 0.993 (0.984-1.000) Glioblastoma 19 82 0.981 (0.959-1.000) All NSCLC 245 159 0.774 (0.728-0.820) Colorectal cancer 40 159 0.978 (0.961-0.996) Breast cancer 38 159 0.821 (0.736-0.906) Pancreatic cancer 35 159 0.987 (0.974-0.999) Glioblastoma 35 159 0.931 (0.890-0.972) Hepatobiliary carcinomas 14 159 0.991 (0.978-1.000) Citation Format: Yue Gao, Chun-Jie Liu, Hua-Yi Li, Xiao-Ming Xiong, Sjors G.j.g. In ‘t Veld, Gui-Ling Li, Jia-Hao Liu, Guang-Yao Cai, Gui-Yan Xie, Shao-Qing Zeng, Yuan Wu, Jian-Hua Chi, Qiong Zhang, Xiao-Fei Jiao, Lin-Li Shi, Wan-Rong Lu, Wei-Guo Lv, Xing-Sheng Yang, Jurgen M.j. Piek, Cornelis D de Kroon, C.a.r. Lok, Anna Supernat, Sylwia Łapińska-Szumczyk, Anna Łojkowska, Anna J. Żaczek, Jacek Jassem, Bakhos A. Tannous, Nik Sol, Edward Post, Myron G. Best, Bei-Hua Kong, Xing Xie, Ding Ma, Thomas Wurdinger, An-Yuan Guo, Qing-Lei Gao. Platelet RNA signature enables early and accurate detection of ovarian cancer: An intercontinental, biomarker identification study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB168.
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Shi, Pei-Yong. "An Interview with Pei-Yong Shi, PhD." Journal of Interferon & Cytokine Research 41, no. 6 (June 1, 2021): 197–99. http://dx.doi.org/10.1089/jir.2021.29022.exp.
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Sun, Hainan, Xiaoyun Dong, Yunzhou Lv, and Libing Huang. "Quercus texana ‘Jin Fen Shi Jia’: A New Colored Landscape Tree." HortScience 58, no. 9 (September 2023): 1093–94. http://dx.doi.org/10.21273/hortsci17187-23.
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Li, huihui, Dongdong Zhou, Zeshun Yv, Yuqian Liao, Jie Huang, Shujuan Sun, fangchao zheng, et al. "Abstract PO3-06-07: Efficacy and safety of sintilimab in combination with anlotinib plus metronomic chemotherapy in advanced triple negative breast cancer (SPACE): preliminary results of a single-arm, multicenter phase II trial." Cancer Research 84, no. 9_Supplement (May 2, 2024): PO3–06–07—PO3–06–07. http://dx.doi.org/10.1158/1538-7445.sabcs23-po3-06-07.
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Abstract Background: Antiangiogenic drugs have demonstrated synergistic effect with anti-PD-1 antibody in advanced triple negative breast cancer (TNBC). Anlotinib is an oral multi-target tyrosine kinase inhibitor (TKI) that strongly inhibits VEGFR, PDGFR, FGFR, and c-kit. Preclinical studies showed that metronomic chemotherapy inhibited angiogenesis and enhanced the efficacy of immunotherapy in TNBC via modulation of the tumor immune microenvironment. We hereby conducted a single-arm, multicenter, phase II trial to investigate the efficacy and safety of sintilimab (anti-PD-1 antibody) plus anlotinib and metronomic chemotherapy as a potential novel therapeutic strategy in advanced TNBC and explore potential biomarkers. Methods: Forty-four cases were planning to be included in this trial. The eligible patients who had received no more than two lines of chemotherapy for metastatic disease were enrolled and received sintilimab (200 mg iv q3w) and anlotinib (12 mg po d1-14 q3w) plus capecitabine (500 mg po, tid) or vinorelbine (40 mg po, tiw) until disease progression or intolerable toxicity. The primary endpoint is objective response rate (ORR) and secondary endpoints are disease control rate (DCR), progression free survival (PFS), and overall survival (OS). The safety profile has also been assessed. Results: As of April 2023, a total of 44 patients were enrolled, and 42 patients were evaluable for efficacy. 3 patients (7.1%) achieved complete response (CR). 6 patients (14.3%) achieved partial response (PR). 25 patients (59.5%) achieved stable disease (SD).The ORR is 21.4% (95%CI 0.103-0.368) and DCR is 81.0% (95%CI 0.810-0.659). The median PFS was 5.06 months (95%CI 2.051-8.069). The most common grade 1 or 2 adverse events (AEs) include elevated thyroid stimulating hormone (52.38%, 22/42), elevated bilirubin (23.81%, 10/42), hand-foot syndrome (22.22%, 8/42), leukopenia (16.67%,7/42), nausea (14.29%, 6/42). Grade 3 AEs include elevated bilirubin (2.38%, 1/42), hypertension (2.38%, 1/42) and herpes zoster (2.38%, 1/42). No grade 4 or 5 AEs occurred. Conclusions: Our date showed that sintilimab in combination with anlotinib plus metronomic chemotherapy have shown favorable efficacy and acceptable safety profile in patients with advanced TNBC. Clinical trial information: ChiCTR2100044725 Citation Format: huihui Li, Dongdong Zhou, Zeshun Yv, Yuqian Liao, Jie Huang, Shujuan Sun, fangchao zheng, Baojiang Li, Shu Fang, Ling Qiang, Guohua Ren, Bing Bu, Pengfei Qiu, Xinzhao Wang, Chao Li, Fangli Cao, Qian Shao, Dali Han, Lihua Song, Baoxuan Zhang, Bingjie Fan, Liang Xu, Xuemei Xie, Xianguang Zhao, Lanping Liu, Wanlong Li, Zhenbo Wang, Changmin Liu, Hui Fu, Xiao Sun, Zhiqiang Shi, Fengxiang Li. Efficacy and safety of sintilimab in combination with anlotinib plus metronomic chemotherapy in advanced triple negative breast cancer (SPACE): preliminary results of a single-arm, multicenter phase II trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-06-07.
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Beardsley, Tim. "SDI: Physicists jib at inducements." Nature 316, no. 6027 (August 1985): 382–83. http://dx.doi.org/10.1038/316382c0.
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Wu, C. Y., Q. Wang, J. Shi, X. Zhang, R. Du, J. Gu, Q. H. Liu, et al. "AB0455 BARICITINIB IN THE TREATMENT OF PATIENTS WITH MODERATE TO SEVERE ACTIVE RHEUMATOID ARTHRITIS IN CHINA: 24-WEEK RESULTS OF POST-MARKETING SAFETY STUDY." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 1418. http://dx.doi.org/10.1136/annrheumdis-2023-eular.2148.
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BackgroundBaricitinib, an orally selective inhibitor of JAK1 and JAK2, was approved for adult patients with moderate-to-severe rheumatoid arthritis (RA) in China. The recommended dose is 2mg once daily and 4mg once daily in patients who have inadequately responded to baricitinib 2mg once daily (for 3 months) or TNF inhibitors. A single-arm, prospective, non-interventional post-marketing safety study (PMSS) was conducted in Chinese RA patients to describe the safety and effectiveness of baricitinib at 24 weeks.ObjectivesTo describe the safety and effectiveness of baricitinib in real-world setting of treating patients with moderate to severe active RA.MethodsThis PMSS (starting July 2020) included 667 patients with RA treated with baricitinib (2 mg or/and 4mg/day) and followed up for 24 weeks. Safety and effectiveness (disease activity) were assessed for 24 weeks. All statistical analyses are descriptive.ResultsSafety analyses included 667 patients (females=82.3%, mean age=53.3 years, mean RA duration 86.9 months). 106 (15.9%) were ≥65 and <75years and 19 (2.8%) were ≥75 years. 29 (4.3%) had previously received biologic therapy. Baricitinib dose regimen was as follows: 2 mg/day, n = 580 (87.0%); 4 mg/day, n = 53 (7.9%); 2/4 mg, n = 34 (5.1%). Concomitant use of MTX and leflunomide occurred in 54.3% and 35.5%, respectively. The overall exposure of baricitinib was 262.1 patient-years; 197 (29.5%) patients withdrew from the study, mostly for patient’s decision (n = 101). Adverse events (AEs) occurred in 250 (37.5%) patients [serious: 28 (4.2%)]. Two patients (0.3%) died: one of pneumonia and one with no cause reported. The incidence of serious infection, herpes zoster and hepatotoxicity was 0.6%, 1.0%, and 3.4%, respectively. No case met laboratory criteria for potential Hy’s Law (ALT/AST ≥3 x ULN and TBL ≥2 x ULN). Malignancy occurred in one patient (thyroid cancer). No venous thromboembolism (VTE) or major adverse cardiovascular event (MACE) were reported during the study observation period (Table 1).In the effectiveness analysis at Week 24, the proportions of patients achieving remission/ low disease activity were 66.6% (235/353) for DAS28-CRP, 64.6% (228/353) for SDAI, and 63.5% (242/381) for CDAI (Figure 1).ConclusionIn conclusion, the safety and effectiveness profile of baricitinib in this Chinese PMSS was generally similar to that in the global RA population with no VTEs or MACE reported and no new safety signals.ReferencesNIL.Table 1.Safety summary among patients with RA treated with baricitinibn (%) PYE [EAIR]Safety Population (N=667)12 weeks24 weeksAE214 (32.08)124.04 [172.52]250 (37.48)198.58 [125.89]AEs related to study treatmentas judged by the investigator95 (14.24)139.99 [67.86]120 (17.99)236.65 [50.71]Death/2 (0.30)261.30 [0.77]SAE22 (3.30)147.03 [14.96]28 (4.20)256.72 [10.91]SAEs related to study treatmentas judged by the investigator8 (1.20)148.32 [5.39]10 (1.50)260.30 [3.84]Treatment discontinuation due to AEs20 (3.00)148.18 [13.50]24 (3.60)260.79 [9.20]AESISerious infection3 (0.45)148.52 [2.02]4 (0.60)260.99 [1.53]Hepatotoxicity16 (2.40)147.13 [10.87]23 (3.45)256.76 [8.96]VTE0148.63 [0.00]0261.30 [0.00]Herpes zoster, n (%)3 (0.45)7 (1.05)Malignancy, n (%)1 (0.15)1 (0.15)MACE, n (%)00Abbreviations: AE= adverse event; AESI= adverse event with special interest; EAIR= exposure-adjusted incidence rate; MACE= major adverse cardiovascular events; N= number of patients in the safety analysis set; n= number of patients in the specified category; PYE= patient-years of exposure; RA= rheumatoid arthritis; SAE= serious adverse event; VTE= venous thromboembolismUsed EAIR per 100 PYE (patient exposure censored at the event).AESI was based on the judgement of investigator recorded in eCRF (electronic case report form)MACE included myocardial infarction, cardiovascular death, and stroke.Acknowledgements:NIL.Disclosure of InterestsChan-yuan Wu: None declared, Qian Wang: None declared, Jian Shi: None declared, XIUYING ZHANG: None declared, Rong Du: None declared, Jieruo Gu: None declared, Qi-huan Liu: None declared, Jiao Yu Employee of: Eli Lilly and Company, Jia-wei Xu Employee of: Eli Lilly and Company, Yan-jie Zhang Employee of: Eli Lilly and Company, Hao Zhu Employee of: Eli Lilly and Company, Mengtao Li: None declared, Xiaofeng Zeng: None declared.
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Zhao, Tianying, Jiajun Shi, Yaohua Yang, Jie Ping, Xiao Ou Shu, Wei Zheng, Jirong Long, and Qiuyin Cai. "Abstract LB045: Transcriptome-wide association study identifies susceptibility loci and genes for lung cancer risk." Cancer Research 83, no. 8_Supplement (April 14, 2023): LB045. http://dx.doi.org/10.1158/1538-7445.am2023-lb045.
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Abstract Objective: Genome-wide association studies (GWAS) have identified more than 50 loci for lung cancer risk. However, susceptibility genes and the underlying mechanisms for these risk loci remain largely unknown. We conducted a transcriptome-wide association study (TWAS) to identify susceptibility genes for lung cancer. Methods: Transcriptome data from normal lung tissue and whole-genome sequencing data from 444 participants of European ancestry in the Genotype-Tissue Expression (GTEx, version 8) were used to build lung-tissue models to predict gene expression levels. Lung-tissue prediction models were successfully established for 10,802 genes with a model performance r > 0.1 and P < 0.05. We also built joint-tissue models using the joint-tissue imputation (JTI) framework, which leverages transcriptome data from lung tissue and 48 other tissue types from the 444 participants in GTEx. Joint-tissue models were successfully established for 12,629 genes with a model performance r > 0.1 and P < 0.05. These prediction models were applied to the GWAS data comprised of 29,266 lung cancer cases and 56,450 controls of European ancestry, in order to evaluate genetically predicted gene expression levels in association with lung cancer risk. Results: We found 44 genes whose genetically predicted expression levels were significantly associated with overall lung cancer risk at the Bonferroni correction significance threshold. Among the 44 genes, four were located at least 500kb away from any of the leading variants identified previously in GWAS. Of these four genes, only the CCHCR1 gene has been reported in previous TWAS, and the other three genes, LY6G5B, PRSS16, and C19orf54, have never been reported in previous GWAS or TWAS. For each of these three novel genes, consistent associations were observed in both lung-tissue and joint-tissue models. For the 40 genes located in previously identified GWAS loci, after adjusting for GWAS-identified variants, the associations for the majority of them became non-significant. However, the associations did not change materially for UCKL1 or PRPF6. These results suggest that the associations for these two genes were independent from previous GWSA-identified signals. We also identified 10 genes located at least 500kb away from GWAS-identified loci that were associated with lung cancer histological subtypes, e.g., adenocarcinoma (DCBLD1 and AQP3), squamous cell carcinoma (ZSCAN26, BLOC1S2, ABCF1, and ZSCAN9), and small cell lung cancer (BTN2A2, TMA16, RP11-218F10.3, and FRS3). An additional 7 genes located in GWAS loci were associated with risk of lung cancer histological subtypes but not with overall lung cancer risk, including 4 genes for adenocarcinoma (TP63, STN1, FAM227B, and TPRG1) and 3 genes for squamous cell carcinoma (DDAH2, OR2H2, and NELFE). Conclusion: Our TWAS identified lung cancer susceptibility genes, providing new insight into the genetics of lung cancer etiology. Citation Format: Tianying Zhao, Jiajun Shi, Yaohua Yang, Jie Ping, Xiao Ou Shu, Wei Zheng, Jirong Long, Qiuyin Cai. Transcriptome-wide association study identifies susceptibility loci and genes for lung cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB045.
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Ueno, Naoto T., Jie Gao, Liming Liu, Rong Shi, Shengxue Liu, Lili Tang, Peizhen Miao, Yang Qiu, Wei Gu, and Cheng Ying. "Abstract CT248: First in human trial of DB1305 in patients with advanced malignant solid tumors." Cancer Research 83, no. 8_Supplement (April 14, 2023): CT248. http://dx.doi.org/10.1158/1538-7445.am2023-ct248.
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Abstract Background: Trophoblast cell-surface antigen 2 (Trop-2) is known as tumor-associated calcium signal transducer 2 (TACSTD2) and plays a role in tumor progression, given its active interplay with several key molecular pathways associated with cancer development and progression. DB-1305 is a Trop-2 antibody-drug conjugate (ADC) composed of a humanized anti-Trop-2 immunoglobulin G1 (IgG1) monoclonal antibody, covalently linked to a proprietary DNA topoisomerase I inhibitor P1021 via a cleavable linker containing maleimide tetrapeptide, with a drug-to-antibody ratio (DAR) of approximately 4. Preclinical in vivo models show that DB-1305 demonstrates robust anti-tumor activity in Trop-2-high triple-negative breast cancer (TNBC), Trop-2-low small cell lung cancer (SCLC) and Trop-2-medium colon cancer but not Trop-2-negative SCLC, demonstrating the dependence of Trop-2 expression for the tumor-suppression activity of DB-1305 and appropriate safety profile supports the intended clinical use. This study aims to evaluate DB-1305 in terms of tolerability and preliminary anti-tumor activity in patients with advanced solid tumors. Methods: This is an open-label, multicenter, multiple-dose, Phase 1/2a study (NCT05438329), including dose escalation Phase 1 and dose-expansion Phase 2a in patients with pretreated advanced solid tumors. Patients should have histologically documented progressed/refractory disease on or after standard systemic anticancer treatments with proven benefits for their disease or without available standard treatments; adequate performance score (ECOG 0-1); adequate organ function and measurable disease as per RECIST v1.1 while without uncontrolled metastatic central nervous system (CNS) involvement and history of interstitial lung diseases. The dose escalation part will evaluate approximately five ascending dose levels of DB-1305 with accelerated titration for the first dose level followed by a “3+3” design for subsequent dose levels to identify the optimal dose, which will enroll up to 70 patients from the United States and China. Upon determining the optimal dose, seven tumor cohorts of 10-40 patients will be included in the dose expansion part, including non-small cell lung cancer, SCLC, hormone receptor-positive breast cancer, and TNBC. DB-1305 will be dosed in both parts until disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity. The primary objectives are evaluating safety tolerability and identifying the optimal dose from Phase 1; assessing safety, tolerability, and objective response rate per RECIST v1.1 from Phase 2a. Secondary objectives include the assessment of the pharmacokinetics and immunogenicity of DB-1305. Exploratory objectives include the assessment of pharmacodynamic biomarkers and Exposure-Response correlation. As of 19 Dec 2022, 20 patients have been enrolled in the dose escalation part. Citation Format: Naoto T. Ueno, Jie Gao, Liming Liu, Rong Shi, Shengxue Liu, Lili Tang, Peizhen Miao, Yang Qiu, Wei Gu, Cheng Ying. First in human trial of DB1305 in patients with advanced malignant solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT248.
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Sun, Yajun, Vijayapal Reddy, Palaniappan Kulanthaivel, Yanwen Feng, Jie Zhao, Zhiyan Chi, Junhao Wang, Lili Shi, Gang Qin, and Paul H. Song. "Abstract 7168: PBI-410 (GQ1010), A novel Trop-2-targeted ADC demonstrates a favorable safety and toxicokinetic profile in multiple preclinical assessments." Cancer Research 84, no. 6_Supplement (March 22, 2024): 7168. http://dx.doi.org/10.1158/1538-7445.am2024-7168.
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Abstract Introduction: Trop-2-targeting ADCs (Trop-2 ADC) have demonstrated notable clinical efficacy; however, safety concerns necessitate frequent dose adjustments or discontinuations. PBI-410 (GQ1010) is a next-generation TROP-2 ADC developed using GeneQuantum's Ligase-Dependent Conjugation (iLDC) technology, that integrates a highly stable linker and a novel camptothecin analogue payload, TopoIx. This study included comprehensive preclinical evaluations that demonstrated a favorable safety and TK profile and potential for broader therapeutic margin versus other Trop-2 ADCs approved or in development. Methods: TopoIx underwent extensive Good Laboratory Practice toxicity assessments in Sprague-Dawley (SD) rats (payload alone) and as part of the intact ADC in Non-Human Primates. Rats were administered repeated intravenous infusions of 0.5, 1.25, and 2.5 mg/kg of H0011 once a week over 5 doses. The potential toxicity profile of PBI-410 was evaluated in cynomolgus monkeys via repeated intravenous infusions of 10, 30, and 60 mg/kg doses every 3 weeks for 3 doses, followed by a six-week recovery phase. Results: TopoIx administration in SD rats exhibited good tolerance, with slight reductions in body weight gain and food consumption. Microscopic tissue changes resolved post-drug withdrawal, except for persistent findings in the sciatic nerve. Repeated doses of PBI-410 in cynomolgus monkeys were well-tolerated, primarily manifesting as skin pigmentation and associated microscopic alterations in specific tissues, such as eyes, esophagus, thymus, and lymph nodes typical for topoisomerase inhibitors. Importantly, these changes were reversible upon drug cessation. The HNSTD/NOAEL for PBI-410 was determined to be 60 mg/kg. This corresponds to mean Cmax of 1760 µg/mL and AUCinf of 235000 µg*hr/mL for ADC and for TopoIx mean Cmax of 16.4 ng/mL and AUCinf of 2610 ng*hr/mL. The lower exposure of TopoIx suggests minimum payload shedding in the systemic circulation. Notably, PBI-410 demonstrated a significantly enhanced safety profile compared to other Topo1-based Trop-2 ADCs, including an absence of hematopoietic and intestinal toxicities, and no pulmonary toxicity or interstitial lung disease (ILD) observed. Conclusion: PBI-410 demonstrated a favorable and differentiated nonclinical safety profile and favorable TK relative to those reported to date for other Trop-2 ADCs in development. This profile, in addition to the potent anti-tumor response and synergistic activity in combination with anti-PD1 reported previously, position PBI-410 as a best-in-class potential Trop-2 ADC and partner of choice for anti-PD1 combination therapy. Additionally, TopoIx has displayed excellent properties among the TOP1 inhibitors, making it suitable for a broader therapeutic application based on exceptional potency while maintaining a favorable safety profile. Citation Format: Yajun Sun, Vijayapal Reddy, Palaniappan Kulanthaivel, Yanwen Feng, Jie Zhao, Zhiyan Chi, Junhao Wang, Lili Shi, Gang Qin, Paul H. Song. PBI-410 (GQ1010), A novel Trop-2-targeted ADC demonstrates a favorable safety and toxicokinetic profile in multiple preclinical assessments [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7168.
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JIANG, JIGANG, WENYING YIN, JIANXIU CHEN, and ERNEST C. BERNARD. "Redescription of Hypogastrura gracilis, synonymy of Ceratophysella quinidentis with C. duplicispinosa, and additional information on C. adexilis (Collembola: Hypogastruridae)." Zootaxa 2822, no. 1 (April 18, 2011): 41. http://dx.doi.org/10.11646/zootaxa.2822.1.2.
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Hypogastrura gracilis Folsom is redescribed from cotypes and Chinese specimens, and a lectotype and 4 paralectotypes are designated. Specimens referable to Ceratophysella adexilis Stach are described. Ceratophysella quinidentis (Jia, Shi & Chen) is reevaluated from type specimens and recognized as a new junior synonym of C. duplicispinosa (Yosii).
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Schmalzer, Sigrid. "Weimin Xiong;, Kedi Wang. He cheng yi ge dan bai zhi: Jie jing niu yi dao su de ren gong quan he cheng [Synthesize a protein: The story of total synthesis of crystalline insulin project in China]. (Zhongguo jin xian dai ke xue ji shu shi yan jiu cong shu.). 194 pp., figs., bibl., app., index. Jinan: Shandong jiao yu chu ban she [Shandong Education Press], 2005. $25 (paper)." Isis 99, no. 1 (March 2008): 231–32. http://dx.doi.org/10.1086/589404.
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Zhang, Lina, Chao Yang, Jie Ma, Yuntao Li, Ruizhen Luo, Jianjun Han, Xiaochun Wang, et al. "Abstract PO2-02-05: CDK4/6 inhibitor dalpiciclib combined with letrozole as neoadjuvant therapy in postmenopausal patients with hormone receptor-positive, HER2-negative stage II-III breast cancer: a single-arm exploratory trial." Cancer Research 84, no. 9_Supplement (May 2, 2024): PO2–02–05—PO2–02–05. http://dx.doi.org/10.1158/1538-7445.sabcs23-po2-02-05.
Full textAbstract:
Abstract Background: Patients with HR-positive, HER2-negative breast cancer respond poorly to neoadjuvant chemotherapy. The phase 3 DAWNA-1 and DAWNA-2 studies have proved that adding dalpiciclib (a CDK4/6 inhibitor) to endocrine therapy can significantly improve progression-free survival in patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer. However, the evidence of dalpiciclib in the neoadjuvant setting is limited. This study aimed to explore the efficacy and safety of dalpiciclib plus letrozole as neoadjuvant therapy in in patients with HR-positive, HER2-negative stage II-III breast cancer. Methods: In this multicenter, single-arm exploratory trial (NCT05512780), adult postmenopausal women with HR-positive (estrogen receptor >10%), HER2-negative stage II-III invasive breast cancer were enrolled. Patients received oral dalpiciclib (150 mg on days 1-21 of each 28-day cycle) and oral letrozole (2.5 mg once daily) for 4 cycles, followed by surgery. The primary endpoint was objective response rate (ORR), assessed by investigator according to the Response Evaluation Criteria In Solid Tumors version 1.1. Secondary endpoints included complete cell cycle arrest (CCCA, defined as Ki-67 < 2.7% on day 15 of the first cycle) rate, total pathological complete response (tpCR; ypT0/is ypN0) rate, residual cancer burden (RCB) 0-I rate, and safety. Results: Between June 2022 and January 2023, 41 patients were screened at 9 sites, and 35 patients were enrolled and received at least one dose of study drug. The median age was 66 years (range, 52-83), and the median baseline Ki-67 level was 20% (range, 4%-40%). The majority of patients had T2 disease (65.7%), lymph node-positive disease (88.6%), and stage II disease (IIA: 45.7%; IIB: 40.0%). The ORR was 35.5% (11/31) at 8 weeks and 51.7% (15/29) at 16 weeks in patients with evaluable response. The CCCA rate was 70.0% (21/30) in patients with available data. Four patients refused surgery and chose to continue the drug therapy. Of 27 patients who had undergone surgery, one (3.7%) patient had tpCR and RCB 0. Of 35 patients, the most common adverse events were neutrophil count decreased (74.3%), white blood cell decreased (68.6%), anemia (34.3%), and fatigue (31.4%). The most common grade 3 or higher adverse event was neutrophil count decreased (45.7%). No febrile neutropenia or treatment-related deaths occurred. Conclusions: This is the first prospective study of neoadjuvant dalpiciclib in patients with HR-positive, HER2-negative breast cancer. The findings suggest the promising tumor response to neoadjuvant dalpiciclib plus letrozole in postmenopausal patients with HR-positive, HER2-negative breast cancer, with a manageable safety profile. This combination can effectively suppress the tumor cell proliferation, as reflected by change in Ki-67 level. Citation Format: Lina Zhang, Chao Yang, Jie Ma, Yuntao Li, Ruizhen Luo, Jianjun Han, Xiaochun Wang, Zhisheng Zhang, Li Ma, Haifeng Cai, Xiangshun Kong, Zunyi Wang, Xinping Zhou, Yueping Liu, JiaJie Shi, Yanshou Zhang, Meiqi Wang, Jiaxing Wang, Cuizhi Geng. CDK4/6 inhibitor dalpiciclib combined with letrozole as neoadjuvant therapy in postmenopausal patients with hormone receptor-positive, HER2-negative stage II-III breast cancer: a single-arm exploratory trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-02-05.