Journal articles on the topic 'Wen hua yan jiu'

Abstract Background: Immune checkpoint inhibitors (ICIs) have heralded a new era in breast cancer treatment; however, response rates remain limited, making precision immune-oncology a major unmet need. In addition to T cells, effective immune responses to ICIs rely on coordinated interactions between innate and adaptive immune cells. Mast cells are evolutionarily conserved, tissue-resident cells of importance to human health. Specific subsets of mast cells might be endowed with opposite roles in cancer treatment, yet the extent of mast cell heterogeneity and its clinical merit in immunotherapy remain undefined. Objective: We sought to comprehensively characterize mast cells in breast cancer, investigate their association with immunotherapy response with in-depth mechanistic insights, and identify actionable strategies to modulate mast cell functional states, thereby optimizing immunotherapy efficacy. Methods: We employed single-cell profiling on longitudinal breast cancer samples from three independent clinical trials (NCT04613674, NCT03197389 and GSE169246) to delineate mast cell heterogeneity in anti-PD-(L)1 therapy. By integrating multi-omic analyses, tissue characterization, preclinical experiments, transgenic mice, and high-throughput drug screening, we outlined the molecular features, underlying mechanisms, and clinical relevance of distinct mast cells to elicit ICI-responsive microenvironments. Subsequently, we launched RENAISSANCE (NCT05076682), a proof-of-concept, Bayesian adaptive, phase 2 platform trial, to evaluate the efficacy and safety of combining mast cell therapeutics with anti-PD-1 backbone therapy in metastatic triple-negative breast cancer (TNBC) patients who progressed after immunotherapy. The primary endpoint was the objective response rate (ORR) assessed using RECIST v1.1 criteria. Results: We identified a distinct population of mast cells termed antigen-presenting mast cells (APMCs), constituting approximately 30% of intratumoral mast cells and correlating with improved clinical benefit of anti-PD-(L)1 therapy in TNBC. APMCs displayed MHC-II and costimulatory molecules, and indicated the presence of tumor-reactive T cells and tertiary lymphoid structures. Using three immunocompetent mouse models, we confirmed the immunomodulatory capacity of APMCs in immunotherapy. Mechanistically, by employing Cpa3CreERT2Cd74fl/fl mice, we demonstrated that APMCs potentiate anti-PD-1 efficacy and antitumor T cell immunity through their antigen-presentation machinery. Interestingly, we identified cromolyn, an FDA-approved drug for allergy, as a potential therapeutic agent that elicited APMC-dependent CD8+ T cell cytotoxicity to synergize with anti-PD-1 therapy. Between February 2022 and March 2023, 10 patients with immunotherapy-refractory metastatic TNBC were enrolled to receive cromolyn plus camrelizumab backbone treatment. Given Bayesian predictive probability, this arm was “graduated” due to meeting the pre-specified efficacy boundary, with an ORR of 40.0% (4/10). The treatment was well tolerated with similar safety profiles of relevant drugs. Conclusions: Our findings provide crucial insights into the impact of mast cell heterogeneity on the clinical response to ICIs at a single-cell level, and pave the way for APMC-directed therapeutic interventions in cancer treatment. To our knowledge, this is the first prospective study in breast cancer of cromolyn plus anti-PD-1 backbone regimen after anti-PD-(L)1 immunotherapy failure, demonstrating significant antitumor activity and commendable tolerability. Consequently, we suggest a phase 3 randomized study to consolidate this finding, which might be an effective treatment in patients for whom there are few effective treatment options. Citation Format: Song-Yang Wu, Xi Jin, Yin Liu, Wen-Jia Zuo, Li Chen, Xiyu Liu, Lei Fan, Zhong-Hua Wang, Yan-Fei Liu, Yi-Zhou Jiang, Zhi-Ming Shao. Programme of mast cell subsets to potentiate breast cancer immunotherapy: from bed to bench to bed (the phase 2 platform RENAISSANCE 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 PO1-14-07.

Abstract Background: Gemcitabine-Cisplatin (GP) chemotherapy is the standard first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). Toripalimab, a humanized IgG4K monoclonal antibody specific for PD-1, in combination with GP chemotherapy showed significant improvement in progression-free survival (PFS) as first-line treatment for RM-NPC at the interim analysis of the JUPITER-02 study (NCT03581786), a randomized, placebo-controlled, double-blinded international Phase III trial. Here we report the results of the final PFS analysis and the interim overall survival (OS) analysis. Methods: Patients (n=289) with advanced NPC with no prior chemotherapy in the recurrent or metastatic setting were randomized (1:1) to receive toripalimab 240 mg (n=146) or placebo (n=143) in combination with gemcitabine and cisplatin every 3 weeks (Q3W) for up to 6 cycles, followed by monotherapy with toripalimab or placebo Q3W until disease progression, intolerable toxicity, or completion of 2 years of treatment. Stratification factors were ECOG PS (0 vs. 1) and extent of disease (recurrent vs. primary metastatic) at enrollment. Tumor response was assessed by a blinded independent review committee (BIRC) per RECIST v1.1. The primary endpoint was PFS by BIRC in the intention-to-treat population. Secondary end points included PFS by investigator, OS, objective response rate (ORR), duration of response (DOR) and safety. Results: At the final PFS analysis, the median follow-up time was 22.1 months for the toripalimab arm and 21.4 months for the placebo arm by the cut-off date of June 8, 2021. The toripalimab arm had a significantly longer PFS than the placebo arm as assessed by BIRC: median PFS 21.4 vs. 8.2 months, HR=0.52 (95% CI: 0.37-0.73), two-sided p<0.0001. The 1-year PFS rates were 59.0% vs. 32.9%. The ORR was 78.8% vs. 67.1% (P=0.022) and the median DOR was 18.0 vs. 6.0 months, HR= 0.49 (95% CI: 0.33-0.72). Consistently, PFS as assessed by investigator was also significantly longer in the toripalimab arm than the placebo arm: median PFS 17.3 vs. 8.1 months, HR=0.43 (95% CI: 0.31-0.58), P<0.0001. As of June 8, 2021, the median OS was not reached in either arm, with a trend favoring the toripalimab arm, HR=0.59 (95% CI: 0.37-0.94), P=0.024. The improvements of PFS and OS in the toripalimab arm were observed across key subgroups, including PD-L1 expression subgroups. Notably, dynamic decrease of plasma Epstein-Barr Virus DNA copy number from baseline was associated with favorable response. No new safety signal was identified. The incidence of Grade ≥3 adverse events (AEs) (89.7% vs 90.2%) and fatal AEs (2.7% vs 2.8%) were similar between the two arms; however, investigator-determined immune-related AEs (irAEs) (53.4% vs. 21.7%) and Grade ≥3 irAEs (8.9% vs. 1.4%) were more frequent in the toripalimab arm. Conclusions: The addition of toripalimab to GP chemotherapy as first-line treatment for advanced NPC had a manageable safety profile and provided superior PFS with a favorable trend in overall survival than chemotherapy alone. Citation Format: Hai-Qiang Mai, Qiu-Yan Chen, Dongping Chen, Chaosu Hu, Kunyu Yang, Jiyu Wen, Jingao Li, Yingrui Shi, Feng Jin, Ruilian Xu, Jianji Pan, Shenhong Qu, Ping Li, Chunhong Hu, Yi-Chun Liu, Yi Jiang, Xia He, Hung-Ming Wang, Wan-Teck Lim, Rui-Hua Xu, Coherus Biosciences and Shanghai Junshi Biosciences. Final progression-free survival analysis of JUPITER-02, a randomized, double-blind, phase 3 study of toripalimab or placebo plus gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma [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 CT226.

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.

The objective duality of the world, man and mankind should correspond to the pairing of Oriental studies and Western studies, however, science and pedagogy know only the first, or orientalistics. This monopoly was the result of the formation of the modern system of sciences in the field of the global domination of the West, representing the East as its opposite — the Non-West and / or interpreting interaction with it in value-asymmetric categories of culture and barbarism. The publication in 2006 of the Russian translation of E. Said's famous anti-Eastern book “Orientalism” and the scientific and educational reform of 2010-2013, provoked a discussion of Russian orientalists in the sense of the concepts of the East and the scientific status of Oriental studies as a complex and supra-branch discipline, which is either a syncretic underscience, or a synthetic superscience. Similar problems have been discussed in Russian Sinology since the 19th, since of all the highly developed cultures of the East, Chinese is the most syncretic, and the science about it is the most synthetic. In traditional China, there were no divisions customary for the West into philosophy and religion / theologians, philosophy and science, humanitarian and natural disciplines, fine and applied arts, etc. Russian Sinology, created at the beginning of the 18th century, corresponded to this specificity, simultaneously with “cutting a window to Europe” to address similar government requests. In the USSR, it was divided into classical Sinology, which was concentrated in Leningrad, with an emphasis on philology and wen-yan, and Soviet Sinology, which was concentrated in Moscow, with an emphasis on history, social studies, and bai-hua. As a result, it was possible to find the most complete reflection in accordance with the standards of classical sinology of the 6-volume encyclopedia “Spiritual Culture of China” (2006-2010). The results of this convergence were also recorded by the 10-volume “History of China from Ancient Times to the Beginning of the 21st Century”, which largely inherited Soviet Sinology (2013-2017). After analyzing these historical phenomena, the article describes the main achievements and problems of Russian Sinology over the past decade and the challenges it faces in the light of the modern rethinking of the scientific status of all oriental studies.

Abstract Chromatin instability has been associated with the expression of structural maintenance of chromosomes (SMC) family members and is a common feature in many tumors. SMC family members have been associated with poor outcomes in several cancer types. However, little is known about their functions and mechanisms in promoting cancer progression, particularly in non-small cell lung cancer (NSCLC). Here, we evaluated the expression of SMC family members in the tumor microenvironment of NSCLC specimens using single-cell RNA sequencing analyses. After a survival analysis, it was found that the sole factor associated with a poor prognosis for NSCLC was member SMC2 expression. Immunohistochemistry was used with data from the Human Protein Atlas, the Cancer Genome Atlas, and the Gene Expression Omnibus databases to confirm the overexpression of SMC2 in NSCLC. We demonstrated that SMC2 regulates not only the fluctuations in the critical states of tumor cells, which are defined by different transcriptome and metabolic properties but also coordinates the immunological components and cell-to-cell communications of the immune milieu, potentially through the pleiotrophin and the Galectin pathways. In vitro and in vivo evidence support the pro-metastatic role of SMC2 in NSCLC. Subsequent investigations showed that SMC2 increases NSCLC progression and metastasis via modulating the ERK/AKT/NF-κB pathway and the epithelial-mesenchymal transition process. Our research clarifies the role and potential mechanisms of SMC2 in NSCLC, providing new treatment options and valuable insights for the management of NSCLC. Citation Format: Yan He, Zhenyu Luo, Yiyao Wang, Shan Xiong, Rui Wan, Xue Zhang, Hua Bai, Jie Wang. SMC2 orchestrates non-small cell lung cancer proliferation, invasion, and metastasis by modulating the ERK/AKT/NF-κB pathways [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 5426.

Abstract Backgrounds: Since human epidermal growth factor receptor 2 (HER2)-positive breast cancers may have different HER2/CEP17 ratios and HER2 copy numbers, outcomes of HER2-positive breast cancer patients treated with anti-HER2 neoadjuvant chemotherapy (NACT) may be different. The aim of this study is to explore the relationship between different groups of HER2 fluorescence in situ hybridization (FISH) positive patterns and response to anti-HER2 NACT. Methods: 513 HER2-positive invasive breast cancers who received anti-HER2 NACT in Fudan University Shanghai Cancer Center, during January 2015 to September 2020, were collected. According to FISH results, 513 patients were divided into three groups. Group A: HER2/CEP17 < 2.0 and HER2 average copy number ≥6.0; Group B: HER2/CEP17≥2.0 and HER2 average copy number ≥4.0 and < 6.0; Group C: HER2/CEP17≥2.0 and HER2 average copy number ≥6.0. Clinicopathological characteristics and pathological complete response(pCR) rates of three groups were analyzed. Results: All 513 patients were treated with anti-HER2 NACT. The anti-HER2 treatment included trastuzumab in 463 (90.3%) patients, trastuzumab plus pertuzumab in 21 (4.1%) patients, trastuzumab plus lapatinib in 3 (0.6%) patients, and trastuzumab plus pyrotinib in 1 (0.2%) patient. 25 (4.9%) cases were unblinded in clinical trials, who were treated either with trastuzumab plus pertuzumab or with trastuzumab plus pyrotinib. Among 513 patients, 237 cases (46.2%)were luminal B (hormone receptor positive and HER2 positive) and 276 cases (53.8%) were hormone receptor negative and HER2 overexpressed (HER2 overexpression type). According to IHC results, cases with HER2 1+,2+ and 3+ were 8 (1.6%), 123 (24.0%) and 382(74.5%), respectively. Among them, 0.0%, 25.2%, and 48.7% achieved pCR (p<0.001). The pCR rate of HER2 overexpression type was higher than that of luminal B type (54.0% vs 28.7%, P<0.001). Lymph nodes with metastasis after NACT in luminal B type was higher than that of HER2 overexpression type (43.0% vs 21.4%, P<0.001). According to HER2-FISH results, 11 cases (2.1%) were group A, 28 cases (5.5%) were group B and 474 cases (92.4%) were group C. Compared with the pCR rate of group A (36.4%) and group C (44.5%), the pCR rate in group B (7.1%) was significantly lower (p<0.001). Conclusions: Among HER2-positive breast cancers, HER2 protein expression level was positively correlated with pCR rate. Luminal B(HER2+)patients benefited less from anti-HER2 NACT than HER2 overexpression patients. Although all were invasive breast cancers with positive HER2-FISH results, patients with HER2/CEP17≥2.0 and HER2 copy number ≥4.0 and <6.0 seemed to respond less favorably to anti-HER2 NACT compared with other groups. The biological characteristics of this group of patients are worthy of further study. Citation Format: Hong Lv, Qian-Ming Bai, Yin Liu, Zhong-Hua Wang, Ruo-Hong Shui, Hong-Fen Lu, Xiao-Li Xu, Bao-Hua Yu, Xiao-Yu Tu, Rui Bi, Yu-Fan Cheng, Xiao-Yan Zhou, Zhi-Min Shao, Wen-Tao Yang. Response to anti-HER2 neoadjuvant chemotherapy in invasive breast cancers with different HER2 FISH-positive patterns [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-11.

Abstract Lung cancer is the most lethal cancer worldwide, with a high incidence of distant metastasis. Many lung adenocarcinoma (LUAD) patients experience brain metastasis during the disease process with unfavorable prognosis. Our previous study has discovered that P4HA1 was exclusively upregulated in brain metastatic cells. Through the analysis of single-cell RNA sequencing of LUAD samples, we found that the expression of P4HA1 in brain metastatic tumor cells is higher than that in primary tumor cells. This finding was further confirmed by immunohistochemical staining. Significantly, a strong presence of P4HA1 in primary tumors is associated with a reduced duration of disease-free survival in individuals with LUAD. Overexpression of P4HA1 in A549 and PC9 cell lines significantly increased the incidence of brain metastasis in BALB/c nude mice, whereas knockdown of P4HA1 in high brain metastatic cells significantly decreased the incidence of brain metastasis and reduced the tumor foci in brain with improved survival. Utilization of DHB, a P4HA1 inhibitor, exerts both therapeutic and preventive effects in relieving brain metastases in nude mice. Furthermore, remarkable inhibition of tumor growth by DHB was observed in patient derived xenograft (PDX) models. RNA sequencing analysis demonstrated that the reduction of P4HA1 expression had a substantial impact on cell adhesion and extracellular matrix (ECM)-receptors interactions. Western blotting analysis verified that the decrease in P4HA1 expression led to a drop in the expression of adhesion molecules ICAM1, VCAM1, NCAM1, as well as integrin molecules ITGA2 and ITGA3. Furthermore, when endothelial cells were co-cultured with conditioned medium from tumor cells, it was observed that the expression of the tight junction molecule ZO1 was reduced after co-culturing with conditioned medium from P4HA1 knockdown A549 cells. The results from the in vitro blood-brain barrier (BBB) model and in vivo biofluorescence imaging indicate that P4HA1 promoted brain metastasis of LUAD via modulating the ability of tumor cells to cross the blood-brain barrier. In conclusion, our study reveals that overexpression of P4HA1 promotes metastatic spread to the brain, and targeting P4HA1 could be a promising therapeutic strategy for the treatment of lung adenocarcinoma brain metastasis. Citation Format: Yan He, Zhenyu Luo, Yucheng Dong, Rui Wan, Xue Zhang, Hua Bai, Jie Wang. Prolyl 4-hydroxylase subunit alpha 1 acts as a novel target for lung adenocarcinoma brain metastasis [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 4139.

<p>1949年後北京故宮輾轉播遷至臺灣，落腳於臺中霧峰北溝(1950-1965)十六年。守護者莊嚴全家也落腳於此，此地乃當時臺中最重要的文化及旅遊勝地。然1965年北溝故宮北遷後，空餘庫房山洞供人憑弔。當時曾出現一批「故宮文學家」，他們與「北溝故宮」有或深或淺的關係，曾留下相關記憶的書寫，這些文本正是本論文考察的對象。職是，本論文以文化空間與文學記憶為論述概念，首論偏安北溝的「回憶空間」，莊嚴父子大半生與故宮文物流離至北溝所構建的回憶空間。其次則論在此文化空間的文人對傳統文化的傳承，即孔德成與臺靜農等人至北溝故宮清點文物的記憶。第三則論及個體記憶的再現，以臺靜農與林文月、凌叔華與蘇雪林的北溝旅行為主。第四則論及集體記憶中的文化旅遊勝地，兼論齊邦媛的英譯暨陪訪史。透過以上討論，可在集體的歷史大敘述外，呈現個體的文學記憶，豐富北溝故宮之文化記憶。</p> <p>&nbsp;</p><p>After 1949, the Palace Museum from Beijing relocated to Taiwan and settled in Beigou北溝 of Taichung (1950-1965) for 16 years. Zhuang Yan莊嚴 and his family who guard the Palace Museum in Beigou北溝故宮 is also setteled here, this place also was the most important cultural tourist attraction in Taichung.However, after the Palace Museum in Beigou北溝故宮 moved northward in 1965, the empty warehouse caves in this area were for people to hang. At that time, a group of &quot; the Palace Museum writers故宮文學家&quot; appeared. They had a deep or shallow relationship with the &quot; the Palace Museum in Beigou北溝故宮&quot;,they had left relevant memory writing,these texts are the objects of this paper. In this paper, the concept of cultural space and literary memory is discussed in this dissertation. Firstly, discussion is about the &ldquo;memory space&rdquo; in Beigou北溝,the memory space constructed by the Zhuang Yan莊嚴 father and son for most of his life and the Palace Museum 故宮’s cultural relics moved to Beigou北溝. Secondly, it discusses the inheritance of traditional culture by the literati in this cultural space, that is, the memory of Kung Te-Cheng孔德成 and Tai Jing-nong臺靜農 and others to the Palace Museum in Beigou北溝故宮 to count the cultural relics. Thirdly, on the reappearance of personal memory, mainly on the the Palace Museum in Beigou北溝故宮 trip of Tai Jing-nong臺靜農 and Lin Wen-yue林文月, Ling Shu-hua凌叔華and Su Xue-lin蘇雪林. Fourthly, the cultural tourism resort in the collective memory, as well as the history of Qi Bang-yuan’s齊邦媛English translation and accompanying visits. Through the above-mentioned discussion, the individual’s literary memory can be presented in addition to the collective grand historical narrative, especially enrich the cultural memory of the Palace Museum in Beigou北溝故宮.</p> <p>&nbsp;</p>

Abstract Background: MET gene amplification is associated with poor prognosis in gastric cancer (GC) and gastroesophageal junction adenocarcinomas (GEJ). Savolitinib is a potent and highly selective oral MET tyrosine-kinase inhibitor. Here we reported the preliminary efficacy and safety from a phase 2 trial of savolitinib monotherapy in patients (pts) with MET-amplified advanced or metastatic GC/GEJ. (NCT04923932). Methods: Eligible pts had 2L+ GEJ or GC, with MET amplification and measurable lesions. Pts received savolitinib at 600 mg QD for body weight (BW) ≥50 kg, while 400 mg QD for BW &lt;50 kg in 21-day cycles until disease progression or meeting other criteria for end of treatment. Savolitinib BID regimen has also been additionally explored. The primary endpoint was objective overall response rate (ORR) evaluated by Independent Review Committee (IRC). One interim analysis (IA) was pre-defined at the first 20 QD pts who had at least 2 tumor assessments. Results: As of IA, 20 pts were enrolled for QD regimen. Demographics and clinical outcomes are shown in table 1. The mean relative dose intensity of 93.07%. Median duration of exposure was 2.09 months. Confirmed ORR by IRC was 45%, and reached 50% in 16 patients with MET GCN (high) while only 1 PR was observed in 4 patients with MET GCN (low). Duration of response rate at 4-month was 85.7% with median follow up time of 5.5 months. The most common Gr≥3 TRAE (≥5%) were platelet count decreased, hypersensitivity, anemia, neutropenia and hepatic function abnormal. In all pts, only 1 patient discontinued treatment due to grade 4 liver function abnormal (TRAE) and no patient died due to TRAE. Conclusion: Savolitinib monotherapy had manageable safety and showed promising efficacy in pts with MET-amplified GEJ or GC, particularly in pts with MET high GCN. BID regimen is being investigated to further evaluate the efficacy and safety of savolitinib in pts with MET high GCN. Table 1. Pts baseline characteristics and clinical efficacy Baseline Characteristics ITT in IA (n=20) Median age (min, max), yearsSex (male/female), nECOG (0/1/2)Median BMI (min, max), (kg/m2)Primary location of tumor (GC/GEJ)Tumor stage (IV)Prior line of therapy (1/2/≥3)MET GCN (high/low) 57.00 (39.5, 76.8)17/33/15/220.8 (14.9, 25.8)16/4205/10/516/4 Clinical Efficacy By IRC By Investigator Confirmed objective response rateDisease control rate4m-DoR rate,% (95% CI) 45%65%85.7 (33.4, 97.9) 40%55%71.4 (25.8, 92.0) Citation Format: Zhi Peng, Hua Wang, Baorui Liu, Huiting Xu, Zhenyang Liu, Tianshu Liu, Jun Zhang, Yuxian Bai, Ying Yuan, Tao Wu, Feng Ye, Qinghua Pan, Jufeng Wang, Enxiao Li, Diansheng Zhong, Yueyin Pan, Yanru Qin, Yan Yang, Yusheng Wang, Aiping Zhou, Yongshun Chen, Dianbao Zhang, Hongli Liu, Xiujuan Qu, Shubin Wang, Ning Liu, Jinsheng Wu, Wei Li, Kejun Nan, Hongming Pan, Jianming Xu, Chunmei Bai, Heling Liu, Jia Wei, Runzhi Chen, Rongrong Li, Wei Li, Jinghong Zhou, Hongyan Yin, Qian Xu, Songhua Fan, Yongxin Ren, Weiguo Su, Lin Shen. A multicenter Phase II study of savolitinib in patients with MET-amplified gastroesophogeal junction adenocarcinomas or gastric 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 CT152.

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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Retraction: “Adipose‐derived mesenchymal stem cells ameliorate the inflammatory reaction in CLP‐induced septic acute lung injury rats via sTNFR1”, by Xian‐Fei Ding, Huo‐Yan Liang, Jun‐Yi Sun, Shao‐Hua Liu, Quan‐Cheng Kan, Le‐Xin Wang, Tong‐Wen Sun, J Cell Physiol. 2019; 234: 16582‐16591: The above article, published online on 18 February 2019 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/full/10.1002/jcp.28329) has been retracted by agreement between the journal's Editor in Chief, Alexander Hutchison, and Wiley Periodicals LLC.The retraction has been agreed following an investigation based on allegations raised by a third party. Several flaws and inconsistencies between results presented and experimental methods described were found. The authors were not able to provide comprehensive experimental data upon request. Thus, the editors consider the conclusions of this article to be invalid. The authors disagree with the retraction.

Graphene-based composites have received a great deal of attention in recent year because the presence of graphene can enhance the conductivity, strength of bulk materials and help create composites with superior qualities. Moreover, the incorporation of metal oxide nanoparticles such as Fe3O4 can improve the catalytic efficiency of composite material. In this work, we have synthesized a composite material with the combination of reduced graphene oxide (rGO), and Fe3O4 modified tissue-paper (mGO-PP) via a simple hydrothermal method, which improved the removal efficiency of the of methylene blue (MB) in water. MB blue is used as the model of contaminant to evaluate the catalytic efficiency of synthesized material by using a Fenton-like reaction. The obtained materials were characterized by SEM, XRD. The removal of materials with methylene blue is investigated by UV-VIS spectroscopy, and the result shows that mGO-PP composite is the potential composite for the color removed which has the removal efficiency reaching 65% in acetate buffer pH = 3 with the optimal time is 7 h. Keywords Graphene-based composite, methylene blue, Fenton-like reaction. References [1] Ma Joshi, Rue Bansal, Reng Purwar, Colour removal from textile effluents, Indian Journal of Fibre & Textile Research, 29 (2004) 239-259 http://nopr.niscair.res.in/handle/123456789/24631.[2] Kannan Nagar, Sundaram Mariappan, Kinetics and mechanism of removal of methylene blue by adsorption on various carbons-a comparative study, Dyes and pigments, 51 (2001) 25-40 https://doi.org/10.1016/S0143-7208(01)00056-0.[3] K Rastogi, J. N Sahu, B. C Meikap, M. 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This paper proposes the concept of multisensory landscape construction, pointing out that people’s perception and appreciation of a landscape is a process of overall impression and judgment formed with a combination of visual, auditory, olfactory, tactile, and even thermal and humid sense. Examples can be found in many famous traditional Chinese gardens. Around the West Lake area, there are famous soundscape scenic spots, e.g., Liu Lang Wen Ying (Orioles Singing in the Willows), Nan Ping Evening Bell (Evening Bell Ringing at the Nanping Hill), Zhejiang Qiu Tao (Autumn Wave of Zhejiang), and Jiu Li Song Tao (Wave of Pine Trees Lasts Nine Miles) . There are also some famous lightscape scenic spots, e.g., San Tan Ying Yue (Moon and Candlelight Mirrored in the Lake) and Ping Hu Qiu Yue (Moon over the Peaceful Lake in Autumn) . In terms of smellscape, in addition to the famous scenic spot Qu Yuan Feng He (Curved Yard and Lotus Pool in Summer), the West Lake area is also widely planted with osmanthus and other fragrant plants, forming a smellscape in which "late autumn is fragrant with osmanthus flowers and lotus in bloom for miles and miles." At Humble Administrator Garden, there are soundscape scenic spots such as Wu Zhu You Ju (Secluded Residence among Bamboo Bushes) and Liu Ting Ge (Pavilion to Pause and Listen); there are smellscape scenic spots such as the Orchid Field, the Magnolia Courtyard, the Panicum Pavilion, etc.; lightscape scenic spots such as Liu Ying Ge (Hall of Reflecting Shadows) and Ta Ying Ting (Pavilion of Shadow of Tower) can also be found there. In Chengde Summer Resort, there are soundscape scenic spots such as Wan He Song Feng (Wind of Ten Thousand Ravines and Pines) and lightscape scenic spots such as Xi Ling Chen Xia (Morning Sunset on West Ridge), etc.; smellscape scenic spots such as Qu Shui Hua Xiang (Fragrance of Flowers in the Curved Water) and Yuan Xiang Tang (Hall of Fragrance of Far Away) can also be found.The above classic cases eloquently prove that the creation of multisensory landscape and the integration of them are the valuable experience in traditional Chinese gardens, which play an important role in the achievement of famous landscape.Therefore, the design of landscape must pay attention to the creation and integration of soundscape, smellscape and lightscape. Another key point of the theory of multisensory landscape construction is that it is necessary to pay attention to both spatial and temporal dimensions so that the constructed landscape can be enjoyed everywhere and at all time periods. In this regard, the creation of the three-scape (specifically refer to soundscape, smellscape and lightscape) can also highlight their regional and temporal characteristics. By analyzing some classic cases of traditional Chinese gardens, this paper proposes that the construction of multisensory landscape and the integration of soundscape, smellscape and lightscape are the valuable experience in traditional Chinese gardens, which are also important for the achievement of famous landscapes and are excellent traditions that we should vigorously inherit and carry forward.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus , is causing a serious worldwide COVID-19 pandemic. The emergence of strains with rapid spread and unpredictable changes is the cause of the increase in morbidity and mortality rates. A number of drugs as well as vaccines are currently being used to relieve symptoms, prevent and treat the disease caused by this virus. However, the number of approved drugs is still very limited due to their effectiveness and side effects. In such a situation, medicinal plants and bioactive compounds are considered a highly valuable source in the development of new antiviral drugs against SARS-CoV-2. This review summarizes medicinal plants and bioactive compounds that have been shown to act on molecular targets involved in the infection and replication of SARS-CoV-2. Keywords: Medicinal plants, bioactive compounds, antivirus, SARS-CoV-2, COVID-19 References [1] R. Lu, X. Zhao, J. Li, P. Niu, B. Yang, H. 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