Xingmei Shu, Ranjiaxi Wang, Yan Liu, Xiaoqian Shi, Yuhao Liu, Yinan Chen, Jinming Shi, Mingyang Liu, Yongmei Song, Dan Li
{"title":"S6K1 overexpression enhances autophagy in breast cancer cells by inducing the translation of CLU.","authors":"Xingmei Shu, Ranjiaxi Wang, Yan Liu, Xiaoqian Shi, Yuhao Liu, Yinan Chen, Jinming Shi, Mingyang Liu, Yongmei Song, Dan Li","doi":"10.1097/CM9.0000000000003596","DOIUrl":"https://doi.org/10.1097/CM9.0000000000003596","url":null,"abstract":"<p><strong>Background: </strong>Ribosomal protein S6 kinase B1 (S6K1) is frequently amplified and correlates with drug resistance and poor prognosis in patients with breast cancer. Although S6K1 functions primarily in the process of translation, the genome-wide translational profiles regulated by S6K1 remain unclear. This study sought to clarify the pivotal role of S6K1 in translational regulation and investigate its novel targets in breast cancer.</p><p><strong>Methods: </strong>Ribosome profiling sequencing (Ribo-seq) was performed to explore genome-wide translational profiles regulated by S6K1 in breast cancer cells. Integrated multiomics analyses, including Ribo-seq, RNA sequencing, and mass spectrometry, were employed to identify a new target of S6K1 translational regulation, the autophagy-related gene clusterin (CLU). Western blotting and immunofluorescence were utilized to confirm that S6K1 regulated CLU translation, thus influencing autophagy in breast cancer cells. Bafilomycin A1 (a late-stage autophagy inhibitor) was used to demonstrate that S6K1 regulated autophagosome formation in breast cancer cells through affecting the translation of CLU.</p><p><strong>Results: </strong>S6K1 depletion resulted in the downregulation of global messenger RNA (mRNA) translation and affected translation in multiple pathways that play crucial roles in carcinogenesis, with autophagy-related pathways being the most prominently affected. The role of S6K1 in autophagy was further confirmed in breast cancer cells, and CLU was identified as a novel target regulated by S6K1 at the translational level. Additionally, the overexpression of S6K1 promoted the translation of CLU, thus facilitating the formation of autophagosomes.</p><p><strong>Conclusion: </strong>This study demonstrated that the overexpression of S6K1 promoted autophagy in breast cancer cells by facilitating the translation of the autophagy-related gene CLU.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in patients with advanced non-small cell lung cancer: A retrospective, multicenter, observational study.","authors":"Yuequan Shi, Xiaoyan Liu, Anwen Liu, Jian Fang, Qingwei Meng, Cuimin Ding, Bin Ai, Yangchun Gu, Cuiying Zhang, Chengzhi Zhou, Yan Wang, Yongjie Shui, Siyuan Yu, Dongming Zhang, Jia Liu, Haoran Zhang, Qing Zhou, Xiaoxing Gao, Minjiang Chen, Jing Zhao, Wei Zhong, Yan Xu, Mengzhao Wang","doi":"10.1097/CM9.0000000000003620","DOIUrl":"https://doi.org/10.1097/CM9.0000000000003620","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to investigate the safety and efficacy of programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) according to different PD-L1 expression statuses in a real-world setting.</p><p><strong>Methods: </strong>This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate.</p><p><strong>Results: </strong>A total of 409 patients, 65.0% (n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% (n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 109/L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 109/L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs.</p><p><strong>Conclusions: </strong>A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hypoxia-inducible factor-prolyl hydroxylase inhibitors in treatment of anemia with chronic disease.","authors":"Zuolin Li, Lan Shen, Yan Tu, Shun Lu, Bicheng Liu","doi":"10.1097/CM9.0000000000003470","DOIUrl":"https://doi.org/10.1097/CM9.0000000000003470","url":null,"abstract":"<p><strong>Abstract: </strong>Anemia of chronic disease (ACD) is the most frequent clinical issue in patients with chronic disease, ACD is usually secondary to chronic kidney disease (CKD), cancer, and chronic infection, which is associated with poor health outcomes, increased morbidity and mortality, and substantial economic costs. Current treatment options for ACD are very limited. The discovery of the hypoxia-inducible factor-prolyl hydroxylase (HIF-PHD) pathway made it possible to develop novel therapeutic agents (such as hypoxia-inducible factor-prolyl hydroxylase inhibitor, HIF-PHI) to treat ACD by stabilizing HIF and subsequently promoting endogenous erythropoietin (EPO) production and iron absorption and utilization. Thus, HIF-PHIs appear to open a new door for the treatment of ACD patients with a novel mechanism. Here, we comprehensively reviewed the latest advancements in the application of HIF-PHIs in ACD. Specifically, we highlighted the key features of HIF-PHIs on ACD, such as stimulation of endogenous EPO, handling iron metabolism, inflammation-independent, and prolonging lifespan of red blood cells. In conclusion, the success of HIF-PHIs in the treatment of ACD may expand the therapeutic opportunity for other types of anemia beyond renal anemia.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Proteomic analysis reveals modulation of key proteins in follicular thyroid cancer progression.","authors":"Xue Cai, Rui Sun, Liang Yang, Nan Yao, Yaoting Sun, Guangmei Zhang, Weigang Ge, Yan Zhou, Zhiqiang Gui, Yu Wang, Haitao Zheng, Dong Xu, Yongfu Zhao, Xiu Nie, Zhiyan Liu, Hao Zhang, Pingping Hu, Honghan Cheng, Zhangzhi Xue, Jiatong Wang, Jing Yu, Chuang Chen, Dingcun Luo, Jingqiang Zhu, Tong Liu, Yifeng Zhang, Qijun Wu, Qiaonan Guo, Wanyuan Chen, Jianbiao Wang, Wenjun Wei, Xiangfeng Lin, Jincao Yao, Guangzhi Wang, Li Peng, Shuyi Liu, Zhihong Wang, Hanqing Liu, Jiaxi Wang, Fan Wu, Zhennan Yuan, Tingting Gong, Yangfan Lv, Jingjing Xiang, Yi Zhu, Lei Xie, Minghua Ge, Haixia Guan, Tiannan Guo","doi":"10.1097/CM9.0000000000003645","DOIUrl":"https://doi.org/10.1097/CM9.0000000000003645","url":null,"abstract":"<p><strong>Background: </strong>Cytopathology cannot be used to reliably distinguish follicular thyroid adenoma (FTA) from follicular thyroid carcinoma (FTC), the second most common form of thyroid cancer, because they exhibit nearly identical cellular morphology. Given the challenges in diagnosis and treatment, this study aims to identify the mechanisms underlying FTC is essential.</p><p><strong>Methods: </strong>Using parallel reaction monitoring-mass spectrometry (PRM-MS) assays, we identified and quantified 94 differentially expressed protein candidates from a retrospective cohort of 1085 FTC and FTA tissue samples from 18 clinical centers. Of these targeted proteins, those with the potential for distinguishing FTC from FTA were prioritized using machine learning. Co-immunoprecipitation (co-IP) and immunofluorescence co-localization assays, as well as gene interference, overexpression, and immunohistochemistry (IHC) experiments, were used to investigate the interactions and cellular functions of selected proteins.</p><p><strong>Results: </strong>Using machine learning models and feature selection methods, 30 of the 94 candidates were prioritized as key proteins. Co-IP and immunofluorescence co-localization assays using FTC cell lines revealed interactions among insulin-like growth factor 2 receptor (IGF2R), major vault protei (MVP), histone deacetylase 1 (HDAC1), and histone H1.5 (H1-5). Gene interference and overexpression experiments in FTC-133 cells confirmed the promotional role of these proteins in cell proliferation. IHC assays of patient samples further confirmed elevated expression of these four proteins in FTC compared with that in FTA.</p><p><strong>Conclusions: </strong>Our findings underscore the utility of advanced proteomic techniques in elucidating the molecular underpinnings of FTC, highlighting the potential significance of IGF2R, MVP, HDAC1, and H1-5 in FTC progression, and providing a foundation for the exploration of targeted therapies.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese Medical JournalPub Date : 2025-05-20Epub Date: 2024-05-09DOI: 10.1097/CM9.0000000000003127
Zhonghong Zeng, Hongying Shan, Mingmei Lin, Siyu Bao, Dan Mo, Feng Deng, Yang Yu, Yihua Yang, Ping Zhou, Rong Li
{"title":"SIRT3 protects endometrial receptivity in patients with polycystic ovary syndrome.","authors":"Zhonghong Zeng, Hongying Shan, Mingmei Lin, Siyu Bao, Dan Mo, Feng Deng, Yang Yu, Yihua Yang, Ping Zhou, Rong Li","doi":"10.1097/CM9.0000000000003127","DOIUrl":"10.1097/CM9.0000000000003127","url":null,"abstract":"<p><strong>Background: </strong>The sirtuin family is well recognized for its crucial involvement in various cellular processes. Nevertheless, studies on its role in the human endometrium are limited. This study aimed to explore the expression and localization of the sirtuin family in the human endometrium, focusing on sirtuin 3 (SIRT3) and its potential role in the oxidative imbalance of the endometrium in polycystic ovary syndrome (PCOS).</p><p><strong>Methods: </strong>Endometrial specimens were collected from both patients with PCOS and controls undergoing hysteroscopy at the Center for Reproductive Medicine, Peking University Third Hospital, from July to August 2015 and used for cell culture. The protective effects of SIRT3 were investigated, and the mechanism of SIRT3 in improving endometrial receptivity of patients with PCOS was determined using various techniques, including cellular bioenergetic analysis, small interfering ribonucleic acid (siRNA) silencing, real-time quantitative polymerase chain reaction, Western blot, immunofluorescence, immunohistochemistry, and flow cytometry analysis.</p><p><strong>Results: </strong>The sirtuin family was widely expressed in the human endometrium, with SIRT3 showing a significant increase in expression in patients with PCOS compared with controls ( P <0.05), as confirmed by protein and gene assays. Concurrently, endometrial antioxidant levels were elevated, while mitochondrial respiratory capacity was reduced, in patients with PCOS ( P <0.05). An endometrial oxidative stress (OS) model revealed that the downregulation of SIRT3 impaired the growth and proliferation status of endometrial cells and reduced their receptivity to day 4 mouse embryos. The results suggested that SIRT3 might be crucial in maintaining normal cellular state by regulating antioxidants, cell proliferation, and apoptosis, thereby contributing to enhanced endometrial receptivity.</p><p><strong>Conclusions: </strong>Our findings proposed a significant role of SIRT3 in improving endometrial receptivity in patients with PCOS by alleviating OS and regulating the balance between cell proliferation and apoptosis. Therefore, SIRT3 could be a promising target for predicting and improving endometrial receptivity in this patient population.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":"1225-1235"},"PeriodicalIF":7.5,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12091677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140891620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese Medical JournalPub Date : 2025-05-20Epub Date: 2025-03-17DOI: 10.1097/CM9.0000000000003498
Yukun Wang, Xingkuo Zhang, Hongjun Wu, Li Xiao, Jie Liu
{"title":"Fine-tuning a large multimodal neural network with clinical and dermoscopic images for accurate detection and histopathological subtype prediction of basal cell carcinoma in long-tailed distributions.","authors":"Yukun Wang, Xingkuo Zhang, Hongjun Wu, Li Xiao, Jie Liu","doi":"10.1097/CM9.0000000000003498","DOIUrl":"10.1097/CM9.0000000000003498","url":null,"abstract":"","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":"1251-1253"},"PeriodicalIF":7.5,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12091604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese Medical JournalPub Date : 2025-05-20Epub Date: 2025-02-28DOI: 10.1097/CM9.0000000000003500
Lan Zhu, Zhangfei Shou, Jinliang Xie, Jianghua Chen, Changxi Wang, Wenli Song, Min Gu, Jing Wu, Martin Blogg, Mohamed Soliman, Ruijin He, Wujun Xue, Zhishui Chen
{"title":"Clinical outcomes of standard vs . delayed initiation of immediate-release tacrolimus following donation after circulatory death in kidney transplantation in China: Results from a randomized controlled trial.","authors":"Lan Zhu, Zhangfei Shou, Jinliang Xie, Jianghua Chen, Changxi Wang, Wenli Song, Min Gu, Jing Wu, Martin Blogg, Mohamed Soliman, Ruijin He, Wujun Xue, Zhishui Chen","doi":"10.1097/CM9.0000000000003500","DOIUrl":"10.1097/CM9.0000000000003500","url":null,"abstract":"","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":"1236-1238"},"PeriodicalIF":7.5,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12091582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}