Chinese Medical Journal最新文献

{"title":"Artificial intelligence-enabled discovery of a RIPK3 inhibitor with neuroprotective effects in an acute glaucoma mouse model.","authors":"Xing Tu, Zixing Zou, Jiahui Li, Simiao Zeng, Zhengchao Luo, Gen Li, Yuanxu Gao, Kang Zhang","doi":"10.1097/CM9.0000000000003387","DOIUrl":"https://doi.org/10.1097/CM9.0000000000003387","url":null,"abstract":"<p><strong>Background: </strong>Retinal ganglion cell (RGC) death caused by acute ocular hypertension is an important characteristic of acute glaucoma. Receptor-interacting protein kinase 3 (RIPK3) that mediates necroptosis is a potential therapeutic target for RGC death. However, the current understanding of the targeting agents and mechanisms of RIPK3 in the treatment of glaucoma remains limited. Notably, artificial intelligence (AI) technologies have significantly advanced drug discovery. This study aimed to discover RIPK3 inhibitor with AI assistance.</p><p><strong>Methods: </strong>An acute ocular hypertension model was used to simulate pathological ocular hypertension in vivo. We employed a series of AI methods, including large language and graph neural network models, to identify the target compounds of RIPK3. Subsequently, these target candidates were validated using molecular simulations (molecular docking, absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction, and molecular dynamics simulations) and biological experiments (Western blotting and fluorescence staining) in vitro and in vivo.</p><p><strong>Results: </strong>AI-driven drug screening techniques have the potential to greatly accelerate drug development. A compound called HG9-91-01, identified using AI methods, exerted neuroprotective effects in acute glaucoma. Our research indicates that all five candidates recommended by AI were able to protect the morphological integrity of RGC cells when exposed to hypoxia and glucose deficiency, and HG9-91-01 showed a higher cell survival rate compared to the other candidates. Furthermore, HG9-91-01 was found to protect the retinal structure and reduce the loss of retinal layers in an acute glaucoma model. It was also observed that the neuroprotective effects of HG9-91-01 were highly correlated with the inhibition of PANoptosis (apoptosis, pyroptosis, and necroptosis). Finally, we found that HG9-91-01 can regulate key proteins related to PANoptosis, indicating that this compound exerts neuroprotective effects in the retina by inhibiting the expression of proteins related to apoptosis, pyroptosis, and necroptosis.</p><p><strong>Conclusion: </strong>AI-enabled drug discovery revealed that HG9-91-01 could serve as a potential treatment for acute glaucoma.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884965","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":"Mechanism of action of the nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome and its regulation in liver injury.","authors":"Yifan Lu, Tianyu Wang, Bo Yu, Kang Xia, Jiayu Guo, Yiting Liu, Xiaoxiong Ma, Long Zhang, Jilin Zou, Zhongbao Chen, Jiangqiao Zhou, Tao Qiu","doi":"10.1097/CM9.0000000000003309","DOIUrl":"https://doi.org/10.1097/CM9.0000000000003309","url":null,"abstract":"<p><strong>Abstract: </strong>Nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) is a cytosolic pattern recognition receptor that recognizes multiple pathogen-associated molecular patterns and damage-associated molecular patterns. It is a cytoplasmic immune factor that responds to cellular stress signals, and it is usually activated after infection or inflammation, forming an NLRP3 inflammasome to protect the body. Aberrant NLRP3 inflammasome activation is reportedly associated with some inflammatory diseases and metabolic diseases. Recently, there have been mounting indications that NLRP3 inflammasomes play an important role in liver injuries caused by a variety of diseases, specifically hepatic ischemia/reperfusion injury, hepatitis, and liver failure. Herein, we summarize new research pertaining to NLRP3 inflammasomes in hepatic injury, hepatitis, and liver failure. The review addresses the potential mechanisms of action of the NLRP3 inflammasome, and its regulation in these liver diseases.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885009","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":"Fecal siderophore genes are potential biomarkers for ulcerative colitis.","authors":"Jingshuang Yan, Rongrong Ren, Zhengpeng Li, Wanyue Dan, Xinyi Ma, Xiaohan Zhang, Xiaoyan Chi, Lihua Peng, Yunsheng Yang","doi":"10.1097/CM9.0000000000003424","DOIUrl":"https://doi.org/10.1097/CM9.0000000000003424","url":null,"abstract":"","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884993","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":"Cardiovascular diseases in patients with cancer: A comprehensive review of epidemiological trends, cardiac complications, and prognostic implications.","authors":"Ali A Alshahrani, Evangelos Kontopantelis, Catharine Morgan, Rathi Ravindrarajah, Glen P Martin, Mamas A Mamas","doi":"10.1097/CM9.0000000000003419","DOIUrl":"https://doi.org/10.1097/CM9.0000000000003419","url":null,"abstract":"<p><strong>Abstract: </strong>This article provides an overview of the current evidence on the epidemiology, overlapping risk factors, and pathophysiology of cardiovascular disease (CVD) in patients with cancer. It explores the cardiotoxic effects of anticancer therapy and their impact on prognosis. Although cancer survival rates have improved over the last two decades, the risk of CVD has risen over time in patients with cancer. CVD and cancer share similar risk factors and a common pathophysiology involving inflammation. Many chemotherapeutic agents used to treat cancer are associated with cardiovascular complications (such as heart failure, myocardial infarction, and thrombosis). Current evidence indicates a significant burden of CVD in patients with cancer, particularly in the first year following cancer diagnosis, with elevated risk persisting beyond this period. This short- and long-term risk of CVD may vary depending on the cancer type and treatment regimen. Early identification of potential cardiovascular risk in patients with cancer, can lead to more favorable clinical and survival outcomes. Given the acute and long-term consequences, patients with cancer require increased cardiovascular care and lifestyle optimization. This article offers valuable insights into the cardiovascular burden and needs of patients with cancer. It is intended for a general medical research readership interested in the intersection of cardiology and oncology.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884966","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":"EZH2/miR-142-3p/HMGB1 axis mediates chondrocyte pyroptosis by regulating endoplasmic reticulum stress in knee osteoarthritis.","authors":"Yang Chen, Shanshan Dong, Xin Zeng, Qing Xu, Mingwei Liang, Guangneng Liao, Lan Li, Bin Shen, Yanrong Lu, Haibo Si","doi":"10.1097/CM9.0000000000003186","DOIUrl":"https://doi.org/10.1097/CM9.0000000000003186","url":null,"abstract":"<p><strong>Background: </strong>Knee osteoarthritis (OA) is still challenging to prevent or treat. Enhanced endoplasmic reticulum (ER) stress and increased pyroptosis in chondrocytes may be responsible for cartilage degeneration. This study aims to investigate the effect of ER stress on chondrocyte pyroptosis and the upstream regulatory mechanisms, which have rarely been reported.</p><p><strong>Methods: </strong>The expression of the histone methyltransferase enhancer of zeste homolog 2 (EZH2), microRNA-142-3p (miR-142-3p), and high mobility group box 1 (HMGB1) and the levels of ER stress, pyroptosis, and metabolic markers in normal and OA chondrocytes were investigated by western blotting, quantitative polymerase chain reaction, immunohistochemistry, fluorescence in situ hybridization, fluorescein amidite-tyrosine-valine-alanine-aspartic acid-fluoromethyl ketone (FAM-YVAD-FMK)/Hoechst 33342/propidium iodide (PI) staining, lactate dehydrogenase (LDH) release assays, and cell viability assessments. The effects of EZH2, miR-142-3p, and HMGB1 on ER stress and pyroptosis and the hierarchical regulatory relationship between them were analyzed by chromatin immunoprecipitation, luciferase reporters, gain/loss-of-function assays, and rescue assays in interleukin (IL)-1β-induced OA chondrocytes. The mechanistic contribution of EZH2, miR-142-3p, and HMGB1 to chondrocyte ER stress and pyroptosis and therapeutic prospects were validated radiologically, histologically, and immunohistochemically in surgically induced OA rats.</p><p><strong>Results: </strong>Increased EZH2 and HMGB1, decreased miR-142-3p, enhanced ER stress, and activated pyroptosis in chondrocytes were associated with OA occurrence and progression. EZH2 and HMGB1 exacerbated and miR-142-3p alleviated ER stress and pyroptosis in OA chondrocytes. EZH2 transcriptionally silenced miR-142-3p via H3K27 trimethylation, and miR-142-3p posttranscriptionally silenced HMGB1 by targeting the 3'-UTR of the HMGB1 gene. Moreover, ER stress mediated the effects of EZH2, miR-142-3p, and HMGB1 on chondrocyte pyroptosis. In vivo experiments mechanistically validated the hierarchical regulatory relationship between EZH2, miR-142-3p, and HMGB1 and their effects on chondrocyte ER stress and pyroptosis.</p><p><strong>Conclusions: </strong>A novel EZH2/miR-142-3p/HMGB1 axis mediates chondrocyte pyroptosis and cartilage degeneration by regulating ER stress in OA, contributing novel mechanistic insights into OA pathogenesis and providing potential targets for future therapeutic research.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863517","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":"Patient-reported quality of life in Asian patients with ER+/HER2- advanced breast cancer treated with palbociclib plus letrozole in the PALOMA-4 trial.","authors":"Binghe Xu, Xichun Hu, Wei Li, Tao Sun, Kunwei Shen, ChiunSheng Huang, Virote Sriuranpong, Roger Kc Ngan, Yee H Chia, Arlene Reisman, Huadong Zhao, Jiayun Shen, Edward Broughton","doi":"10.1097/CM9.0000000000003122","DOIUrl":"https://doi.org/10.1097/CM9.0000000000003122","url":null,"abstract":"<p><strong>Background: </strong>Palbociclib plus an aromatase inhibitor is approved for treatment of patients with ER+/HER2- advanced breast cancer (ABC). In the PALOMA-4 trial, adding palbociclib to letrozole prolonged median progression-free survival in Asian women with ER+/HER2- ABC. Here, we report patient-reported outcomes (PROs) from PALOMA-4.</p><p><strong>Methods: </strong>PALOMA-4 was a randomized, double-blind, phase 3 trial of palbociclib plus letrozole vs. placebo plus letrozole treatment in postmenopausal Asian women with ER+/HER2- ABC. PROs were longitudinally assessed using the Functional Assessment of Cancer Therapy-Breast (FACT-B) and EuroQoL 5D three level (EQ-5D-3L) questionnaires. Group comparisons were analyzed using longitudinal, mixed-effects models.</p><p><strong>Results: </strong>Patients were randomly assigned to palbociclib plus letrozole (n = 169) or placebo plus letrozole (n = 171) treated groups. No significant between-arm differences in change from baseline were observed in FACT-B and its subscales, or the EQ-5D-3L index. A significant, but not clinically meaningful difference was observed in change from baseline in mean EQ-VAS score favoring palbociclib plus letrozole (3.36; 95% confidence interval [CI], 0.88-5.83; P = 0.008). When patients from both arms were combined, significant differences in the mean change from baseline for FACT-B total were observed favoring treatment responders vs. non-responders (3.84; 95% CI, 0.33-7.36; P = 0.032) and for the Breast Cancer Subscale favoring patients without disease progression vs. those with progression (0.97; 95% CI, 0.05-1.89; P = 0.038).</p><p><strong>Conclusions: </strong>Quality of life was maintained when palbociclib was added to letrozole in Asian women with ABC. These findings are consistent with PALOMA-2 results and support the use of palbociclib as first-line treatment in postmenopausal Asian patients with ER+/HER2- ABC.</p><p><strong>Registration: </strong>clinicaltrials.gov, NCT02297438.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853042","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":"Intelligent imaging technology applications in multidisciplinary hospitals: A systematic review.","authors":"Ke Fan, Lei Yang, Fei Ren, Xueyuan Zhang, Bo Liu, Ze Zhao, Jianwen Gu","doi":"10.1097/CM9.0000000000003436","DOIUrl":"https://doi.org/10.1097/CM9.0000000000003436","url":null,"abstract":"<p><strong>Abstract: </strong>With the rapid development of artificial intelligence technology, its applications in medical imaging have become increasingly extensive. This review aimed to analyze the current development status and future direction of intelligent imaging technology by investigating its application in various medical departments. To achieve this, we conducted a comprehensive search of various data sources up to 2024, including PubMed, Web of Science, and Google Scholar, based on the principle of comprehensive search. A total of 332 articles were screened, and after applying the inclusion and exclusion criteria, 56 articles were selected for this study. According to the findings, intelligent imaging technology exhibits robust image recognition capabilities, making it applicable across diverse medical imaging modalities within hospital departments. This technology offers an efficient solution for the analysis of various medical images by extracting and accurately identifying complex features. Consequently, it significantly aids in the detection and diagnosis of clinical diseases. Its high accuracy, sensitivity, and specificity render it an indispensable tool in clinical diagnostics and related tasks, thereby enhancing the overall quality of healthcare services. The application of intelligent imaging technology in healthcare significantly enhances the efficiency of clinical diagnostics, resulting in more accurate and timely patient assessments. This advanced technology offers a faster and more precise diagnostic approach, ultimately improving patient care and outcomes. This review analyzed the socioeconomic changes brought about by intelligent imaging technology to provide a more comprehensive evaluation. Also, we systematically analyzed the current shortcomings of intelligent imaging technology and its future development directions, to enable future research.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845876","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":"Development of physical technology plays an important role in reducing radiation-induced lung injury.","authors":"Han Bai, Jie Bai, Li Wang, Xuhong Liu, Xiang Pan, Qianyan Li, Feifei Deng","doi":"10.1097/CM9.0000000000003418","DOIUrl":"https://doi.org/10.1097/CM9.0000000000003418","url":null,"abstract":"","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834348","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":"CAR-based cell therapies for systemic lupus erythematosus.","authors":"Yiyang Wang, Liangjing Lu, Shuang Ye, Qiong Fu","doi":"10.1097/CM9.0000000000003406","DOIUrl":"https://doi.org/10.1097/CM9.0000000000003406","url":null,"abstract":"<p><strong>Abstract: </strong>The remarkable efficacy of chimeric antigen receptor (CAR) T cell therapy in hematological malignancies has provided a solid basis for the therapeutic concept, wherein specific pathogenic cell populations can be eradicated by means of targeted recognition. During the past few years, CAR-based cell therapies have been extensively investigated in preclinical and clinical research across various non-tumor diseases, with particular emphasis in the treatment of autoimmune diseases (ADs), yielding significant advancements. The recent deployment of CD19-directed CAR T cells has induced long-lasting, drug-free remission in patients with systemic lupus erythematosus (SLE) and other systemic AD, alongside a more profound immune reconstruction of B cell repertoire compared with conventional immunosuppressive agents and B cell-targeting biologics. Despite the initial success achieved by CAR T cell therapy, it is critical to acknowledge the divergences in its application between cancer and AD. Through examining recent clinical studies and ongoing research, we highlight the transformative potential of this therapeutic approach in the treatment of SLE, while also addressing the challenges and future directions necessary to enhance the long-term efficacy and safety of CAR-based cell therapies in clinical practice.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834347","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":"Recent global patterns in skin cancer incidence, mortality, and prevalence.","authors":"Mingyue Wang, Xinghua Gao, Li Zhang","doi":"10.1097/CM9.0000000000003416","DOIUrl":"https://doi.org/10.1097/CM9.0000000000003416","url":null,"abstract":"<p><strong>Background: </strong>Skin cancer is a common skin disease whose incidence and mortality rates have been showing yearly increases. In this report, we update the most recent data on skin cancer as obtained from GLOBOCAN 2022.</p><p><strong>Methods: </strong>The incidence and mortality rates of skin cancer (melanoma of skin and non-melanoma skin cancer) in GLOBOCAN 2022 were reviewed. These data were analyzed and the characteristics of incidence and mortality across five continents and top five countries in each continent are presented. In addition, correlations between Human Development Index (HDI) and age-standardized incidence and mortality rates of these two skin cancers are described.</p><p><strong>Results: </strong>The GLOBOCAN 2022 data indicated that melanoma was the 17th most common cancer. An estimated 331,722 people were diagnosed with melanoma globally and approximately 58,667 died from this disease. For non-melanoma skin cancer, it ranks as the 5th most common cancer, and estimated 1,234,533 people were diagnosed with non-melanoma skin cancer globally and approximately 69,416 died from this disease. The incidence of skin cancer varies across geographic regions and countries, with a predominance observed in Oceania, North America, and Europe. Australia was ranked first in terms of incidence, while incidence rates in Africa and Asia were very low. Despite these regional differences in incidence, there was little geographic variation in mortality rates. Currently, the number of deaths from non-melanoma skin cancer exceeds that of melanoma of skin. HDI was positively associated with the incidence of both types of skin cancers, with a positive correlation obtained between HDI and mortality from melanoma of skin and a negative correlation between HDI and mortality from non-melanoma skin cancer.</p><p><strong>Conclusions: </strong>Skin cancer remains a major disease burden worldwide. Substantial variations are observed across countries and regions with incidence rates being greater in Caucasians, the elderly, and in groups with prolonged exposures to ultraviolet rays. Further research on skin cancer will be required to provide a rationale for more effective preventions and treatments of this condition.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834350","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}