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Irisin alleviates hepatic steatosis by activating the autophagic SIRT3 pathway.
IF 7.5 3区 医学
Chinese Medical Journal Pub Date : 2025-02-18 DOI: 10.1097/CM9.0000000000003427
Ying Zhao, Jia Li, Anran Ma, Zhihong Wang, Yunzhi Ni, Di Wu, Yue Zhou, Na Zhang, Li Zhang, Yongsheng Chang, Qinghua Wang
{"title":"Irisin alleviates hepatic steatosis by activating the autophagic SIRT3 pathway.","authors":"Ying Zhao, Jia Li, Anran Ma, Zhihong Wang, Yunzhi Ni, Di Wu, Yue Zhou, Na Zhang, Li Zhang, Yongsheng Chang, Qinghua Wang","doi":"10.1097/CM9.0000000000003427","DOIUrl":"https://doi.org/10.1097/CM9.0000000000003427","url":null,"abstract":"<p><strong>Background: </strong>Disruption of hepatic lipid homeostasis leads to excessive hepatic triglyceride accumulation and the development of metabolic dysfunction-associated steatotic liver disease (MASLD). Autophagy, a critical process in liver lipid metabolism, is impaired in MASLD pathogenesis. Irisin, a skeletal muscle-driven myokine, regulates lipid metabolism, but its impact on hepatic lipid metabolism is not well understood. Here, we aimed to explore the role of irisin in hepatic steatosis and the underlying mechanisms involved.</p><p><strong>Methods: </strong>A high-fat diet (HFD)-induced MASLD mouse model was used, and the recombinant irisin protein, herein referred to as \"Irisin\", was intraperitoneally administered for 4 weeks to evaluate the effects of irisin on hepatic lipid accumulation. Liver tissues were stained with Oil red O (ORO), and triglyceride (TG) and total cholesterol (TC) contents were measured in serum and liver homogenates. The expression of the autophagosome marker microtubule-associated protein 1 light chain 3 (LC3), the autophagy receptor protein sequestosome-1 (SQSTM1/p62), autophagy initiation complex unc-51-like kinase 1 (ULK1) and the lysosomal functional protein cathepsin B was measured via Western blotting, and the expression of the transcription factor EB (TFEB) was analyzed via immunofluorescence to explore autophagic changes. The effect of irisin on autophagic flux was further evaluated in palmitic acid-induced HepG2 cells by measuring autophagic degradation with chloroquine (CQ), and analyzing the colocalization of LC3 and lysosome-associated protein 1 (LAMP1). The possible mechanism was examined by measuring the expression of the autophagic sirtuin 3 (SIRT3) pathway and further validated using overexpression of SIRT3 with plasmid transfection or siRNA-mediated knockdown. Student's t-test was utilized for statistical analysis.</p><p><strong>Results: </strong>Irisin significantly reduces hepatic lipid accumulation in mice fed with HFD, accompanied by enhanced hepatocyte autophagy and upregulation of the SIRT3 pathway. In HepG2 cells, Irisin attenuated palmitic acid-induced lipid accumulation, which was partially dependent on SIRT3 levels. Mechanistically, Irisin treatment upregulated SIRT3 and phosphorylated AMP-activated protein kinase (AMPK), inhibited mammalian target of rapamycin (mTOR) activity, promoted TFEB nucleus translocation, increased cathepsin B expression, enhanced autophagic degradation, and alleviated hepatic steatosis. No significant changes in phosphorylation of ULK1 in the hepatocytes were observed. However, when siRNA was used to knock down SIRT3, the changes of those protein were partially reversed, and hepatic steatosis was further exacerbated.</p><p><strong>Conclusions: </strong>Our findings highlight irisin as a potential therapeutic for hepatic steatosis by modulating autophagy and lipid metabolism, potentially providing a novel therapeutic target for the management of MASLD. ","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448414","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}
引用次数: 0
Targeting synthetic lethality in colorectal cancer.
IF 7.5 3区 医学
Chinese Medical Journal Pub Date : 2025-02-18 DOI: 10.1097/CM9.0000000000003511
Pingting Chen, Junsha An, Jianbo Zhou, Jiayu Zou, Cheng Peng, Fu Peng
{"title":"Targeting synthetic lethality in colorectal cancer.","authors":"Pingting Chen, Junsha An, Jianbo Zhou, Jiayu Zou, Cheng Peng, Fu Peng","doi":"10.1097/CM9.0000000000003511","DOIUrl":"https://doi.org/10.1097/CM9.0000000000003511","url":null,"abstract":"","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448422","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}
引用次数: 0
Long-term clinical outcomes of wedge osteotomy of hemivertebra for adolescent patients with congenital scoliosis.
IF 7.5 3区 医学
Chinese Medical Journal Pub Date : 2025-02-18 DOI: 10.1097/CM9.0000000000003487
Fan Feng, Lingfeng Xu, Zude Liu, Xiuyuan Chen, Yucheng Ji, Bin Chen, Hongxing Shen, Lifeng Lao
{"title":"Long-term clinical outcomes of wedge osteotomy of hemivertebra for adolescent patients with congenital scoliosis.","authors":"Fan Feng, Lingfeng Xu, Zude Liu, Xiuyuan Chen, Yucheng Ji, Bin Chen, Hongxing Shen, Lifeng Lao","doi":"10.1097/CM9.0000000000003487","DOIUrl":"https://doi.org/10.1097/CM9.0000000000003487","url":null,"abstract":"","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448416","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}
引用次数: 0
Effects of psychological stress on inflammatory bowel disease via affecting the microbiota-gut-brain axis.
IF 7.5 3区 医学
Chinese Medical Journal Pub Date : 2025-02-18 DOI: 10.1097/CM9.0000000000003389
Yuhan Chen, Xiaofen Chen, Suqin Lin, Shengjun Huang, Lijuan Li, Mingzhi Hong, Jianzhou Li, Lili Ma, Juan Ma
{"title":"Effects of psychological stress on inflammatory bowel disease via affecting the microbiota-gut-brain axis.","authors":"Yuhan Chen, Xiaofen Chen, Suqin Lin, Shengjun Huang, Lijuan Li, Mingzhi Hong, Jianzhou Li, Lili Ma, Juan Ma","doi":"10.1097/CM9.0000000000003389","DOIUrl":"https://doi.org/10.1097/CM9.0000000000003389","url":null,"abstract":"<p><strong>Abstract: </strong>Inflammatory bowel disease (IBD) is an idiopathic intestinal inflammatory condition with chronic and relapsing manifestations and is characterized by a disturbance in the interplay between the intestinal microbiota, the gut, and the brain. The microbiota-gut-brain axis involves interactions among the nervous system, the neuroendocrine system, the gut microbiota, and the host immune system. Increasing published data indicate that psychological stress exacerbates the severity of IBD due to its negative effects on the microbiota-gut-brain axis, including alterations in the stress response of the hypothalamic-pituitary-adrenal (HPA) axis, the balance between the sympathetic nervous system and vagus nerves, the homeostasis of the intestinal flora and metabolites, and normal intestinal immunity and permeability. Although the current evidence is insufficient, psychotropic agents, psychotherapies, and interventions targeting the microbiota-gut-brain axis show the potential to improve symptoms and quality of life in IBD patients. Therefore, further studies that translate recent findings into therapeutic approaches that improve both physical and psychological well-being are needed.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448411","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}
引用次数: 0
Clinical and hematological factors affecting perioperative blood loss following total knee arthroplasty: A new clinical prediction model.
IF 7.5 3区 医学
Chinese Medical Journal Pub Date : 2025-02-13 DOI: 10.1097/CM9.0000000000003519
Hengyan Zhang, Xuemeng Mu, Zheping Zhang, Jin Lin, Jin Jin, Wenwei Qian, Bin Feng, Xisheng Weng
{"title":"Clinical and hematological factors affecting perioperative blood loss following total knee arthroplasty: A new clinical prediction model.","authors":"Hengyan Zhang, Xuemeng Mu, Zheping Zhang, Jin Lin, Jin Jin, Wenwei Qian, Bin Feng, Xisheng Weng","doi":"10.1097/CM9.0000000000003519","DOIUrl":"https://doi.org/10.1097/CM9.0000000000003519","url":null,"abstract":"","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413602","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}
引用次数: 0
Development and multicenter validation of machine learning models for predicting postoperative pulmonary complications after neurosurgery.
IF 7.5 3区 医学
Chinese Medical Journal Pub Date : 2025-02-13 DOI: 10.1097/CM9.0000000000003433
Ming Xu, Wenhao Zhu, Siyu Hou, Hongzhi Xu, Jingwen Xia, Liyu Lin, Hao Fu, Mingyu You, Jiafeng Wang, Zhi Xie, Xiaohong Wen, Yingwei Wang
{"title":"Development and multicenter validation of machine learning models for predicting postoperative pulmonary complications after neurosurgery.","authors":"Ming Xu, Wenhao Zhu, Siyu Hou, Hongzhi Xu, Jingwen Xia, Liyu Lin, Hao Fu, Mingyu You, Jiafeng Wang, Zhi Xie, Xiaohong Wen, Yingwei Wang","doi":"10.1097/CM9.0000000000003433","DOIUrl":"https://doi.org/10.1097/CM9.0000000000003433","url":null,"abstract":"<p><strong>Background: </strong>Postoperative pulmonary complications (PPCs) are major adverse events in neurosurgical patients. This study aimed to develop and validate machine learning models predicting PPCs after neurosurgery.</p><p><strong>Methods: </strong>PPCs were defined according to the European Perioperative Clinical Outcome standards as occurring within 7 postoperative days. Data of cases meeting inclusion/exclusion criteria were extracted from the anesthesia information management system to create three datasets: The development (data of Huashan Hospital, Fudan University from 2018 to 2020), temporal validation (data of Huashan Hospital, Fudan University in 2021) and external validation (data of other three hospitals in 2023) datasets. Machine learning models of six algorithms were trained using either 35 retrievable and plausible features or the 11 features selected by Lasso regression. Temporal validation was conducted for all models and the 11-feature models were also externally validated. Independent risk factors were identified and feature importance in top models was analyzed.</p><p><strong>Results: </strong>PPCs occurred in 712 of 7533 (9.5%), 258 of 2824 (9.1%), and 207 of 2300 (9.0%) patients in the development, temporal validation and external validation datasets, respectively. During cross-validation training, all models except Bayes demonstrated good discrimination with an area under the receiver operating characteristic curve (AUC) of 0.84. In temporal validation of full-feature models, deep neural network (DNN) performed the best with an AUC of 0.835 (95% confidence interval [CI]: 0.805-0.858) and a Brier score of 0.069, followed by logistic regression (LR), random forest and XGBoost. The 11-feature models performed comparable to full-feature models with very close but statistically lower AUCs, with the top models of DNN and LR in temporal and external validations. An 11-feature nomogram was drawn based on the LR algorithm and it outperformed the minimally modified Assess respiratory RIsk in Surgical patients in CATalonia (ARISCAT) and Laparoscopic Surgery Video Educational Guidelines (LAS VEGAS) scores with a higher AUC (LR: 0.824, ARISCAT: 0.672, LAS: 0.663). Independent risk factors based on multivariate LR mostly overlapped with Lasso-selected features, but lacked consistency with the important features using the Shapley additive explanation (SHAP) method of the LR model.</p><p><strong>Conclusions: </strong>The developed models, especially the DNN model and the nomogram, had good discrimination and calibration, and could be used for predicting PPCs in neurosurgical patients. The establishment of machine learning models and the ascertainment of risk factors might assist clinical decision support for improving surgical outcomes.</p><p><strong>Trial registration: </strong>ChiCTR 2100047474; https://www.chictr.org.cn/showproj.html?proj = 128279.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413604","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}
引用次数: 0
FMRP, an RNA-binding protein induced by the Mycoplasma pneumonia CARDS toxin, regulates multiciliogenesis and inflammation. FMRP是一种由肺炎支原体CARDS毒素诱导的RNA结合蛋白,可调节多纤毛生成和炎症。
IF 7.5 3区 医学
Chinese Medical Journal Pub Date : 2025-02-11 DOI: 10.1097/CM9.0000000000003474
Yuling Xu, Tingyu Yang, Shuai Shao, Fengjiao Liu, Nan Song, Jieqiong Li
{"title":"FMRP, an RNA-binding protein induced by the Mycoplasma pneumonia CARDS toxin, regulates multiciliogenesis and inflammation.","authors":"Yuling Xu, Tingyu Yang, Shuai Shao, Fengjiao Liu, Nan Song, Jieqiong Li","doi":"10.1097/CM9.0000000000003474","DOIUrl":"https://doi.org/10.1097/CM9.0000000000003474","url":null,"abstract":"","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390298","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}
引用次数: 0
Intracranial artery stenosis is associated with retinal arteriolar deficit.
IF 7.5 3区 医学
Chinese Medical Journal Pub Date : 2025-02-11 DOI: 10.1097/CM9.0000000000003453
Le Cao, Hang Wang, Zhouwei Xiong, William Robert Kwapong, Yuying Yan, Jinkui Hao, Guina Liu, Yitian Zhao, Bo Wu
{"title":"Intracranial artery stenosis is associated with retinal arteriolar deficit.","authors":"Le Cao, Hang Wang, Zhouwei Xiong, William Robert Kwapong, Yuying Yan, Jinkui Hao, Guina Liu, Yitian Zhao, Bo Wu","doi":"10.1097/CM9.0000000000003453","DOIUrl":"https://doi.org/10.1097/CM9.0000000000003453","url":null,"abstract":"","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390393","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}
引用次数: 0
RNF115 deficiency upregulates autophagy and inhibits hepatocellular carcinoma growth.
IF 7.5 3区 医学
Chinese Medical Journal Pub Date : 2025-02-11 DOI: 10.1097/CM9.0000000000003466
Zhaohui Gu, Jinqiu Feng, Shufang Ye, Tao Li, Yaxin Lou, Pengli Guo, Ping Lv, Zongming Zhang, Bin Zhu, Yingyu Chen
{"title":"RNF115 deficiency upregulates autophagy and inhibits hepatocellular carcinoma growth.","authors":"Zhaohui Gu, Jinqiu Feng, Shufang Ye, Tao Li, Yaxin Lou, Pengli Guo, Ping Lv, Zongming Zhang, Bin Zhu, Yingyu Chen","doi":"10.1097/CM9.0000000000003466","DOIUrl":"https://doi.org/10.1097/CM9.0000000000003466","url":null,"abstract":"","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390395","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}
引用次数: 0
Poly(ADP-ribose) polymerase inhibitors in cancer therapy.
IF 7.5 3区 医学
Chinese Medical Journal Pub Date : 2025-02-11 DOI: 10.1097/CM9.0000000000003471
Ziqi Zhu, Yujun Shi
{"title":"Poly(ADP-ribose) polymerase inhibitors in cancer therapy.","authors":"Ziqi Zhu, Yujun Shi","doi":"10.1097/CM9.0000000000003471","DOIUrl":"https://doi.org/10.1097/CM9.0000000000003471","url":null,"abstract":"<p><strong>Abstract: </strong>Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) have emerged as critical agents for cancer therapy. By inhibiting the catalytic activity of PARP enzymes and trapping them in the DNA, PARPis disrupt DNA repair, ultimately leading to cell death, particularly in cancer cells with homologous recombination repair deficiencies, such as those harboring BRCA mutations. This review delves into the mechanisms of action of PARPis in anticancer treatments, including the inhibition of DNA repair, synthetic lethality, and replication stress. Furthermore, the clinical applications of PARPis in various cancers and their adverse effects as well as their combinations with other therapies and the mechanisms underlying resistance are summarized. This review provides comprehensive insights into the role and mechanisms of PARP and PARPis in DNA repair, with a particular focus on the potential of PARPi-based therapies in precision medicine for cancer treatment.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390394","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}
引用次数: 0
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