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Des-Arg(9)bradykinin as a causal metabolite for autism spectrum disorder

World Journal of Psychiatry 2024年第1期14卷 88-101页

作者： Zhong-Yu Huang Zi-Pan Lyu Hong-Gui Li Hua-Zhi You Xiang-Na Yang Cai-Hui Cha Center for medical Research on Innovation and Translation Institute of Clinical MedicineGuangzhou First People’s HospitalSchool of MedicineSouth China University of TechnologyGuangzhou 510000Guangdong ProvinceChina School of Biological Sciences Nanyang Technological UniversityNanyang Ave 639798Singapore Department of Pediatrics First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510405Guangdong ProvinceChina Department of Nutrition First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510405Guangdong ProvinceChina Department of Pediatric Traditional Chinese Medicine Clinic Guangzhou Women and Children's Medical CenterGuangzhou 510632Guangdong ProvinceChina Department of Psychology Guangzhou Women and Children's Medical CenterGuangzhou 510632Guangdong ProvinceChina

BACKGROUND Early diagnosis and therapeutic interventions can greatly enhance the developmental trajectory of children with autism spectrum disorder(ASD).However,the etiology of ASD is not completely understood.The presence of confounding factors from environment and genetics has increased the difficulty of the identification of diagnostic biomarkers for ASD.AIM To estimate and interpret the causal relationship between ASD and metabolite profile,taking into consideration both genetic and environmental influences.METHODS A two-sample Mendelian randomization(MR)analysis was conducted using summarized data from large-scale genome-wide association studies(GWAS)including a metabolite GWAS dataset covering 453 metabolites from 7824 European and an ASD GWAS dataset comprising 18381 ASD cases and 27969 healthy controls.Metabolites in plasma were set as exposures with ASD as the main outcome.The causal relationships were estimated using the inverse variant weight(IVW)algorithm.We also performed leave-one-out sensitivity tests to validate the robustness of the results.Based on the drafted metabolites,enrichment analysis was conducted to interpret the association via constructing a protein-protein interaction network with multi-scale evidence from databases including Infinome,SwissTargetPrediction,STRING,and Metascape.RESULTS Des-Arg(9)-bradykinin was identified as a causal metabolite that increases the risk of ASD(β=0.262,SE=0.064,P_(IVW)=4.64×10^(-5)).The association was robust,with no significant heterogeneity among instrument variables(P_(MR Egger)=0.663,P_(IVW)=0.906)and no evidence of pleiotropy(P=0.949).Neuroinflammation and the response to stimulus were suggested as potential biological processes mediating the association between Des-Arg(9)bradykinin and ASD.CONCLUSION Through the application of MR,this study provides practical insights into the potential causal association between plasma metabolites and ASD.These findings offer perspectives for the discovery of diagnostic or predictive biomarkers to support clinical

关键词： Des-Arg(9)bradykinin Autism spectrum disorder Mendelian randomization Metabolite Enrichment analysis

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Elevated Kallistatin promotes the occurrence and progression of non-alcoholic fatty liver disease

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1730-1744页

作者： Zhenzhen Fang Gang Shen Yina Wang Fuyan Hong Xiumei Tang Yongcheng Zeng Ting Zhang Huanyi Liu Yanmei Li Jinhong Wang Jing Zhang Anton Gao Weiwei Qi Xia Yang Ti Zhou Guoquan Gao Department of Biochemistry Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhou 510080China Department of VIP medical Center the Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510080China Physical Examination Center the Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510080China Department of Clinical Laboratory Guangzhou First People's HospitalGuangzhou 510080China Guangdong Key Laboratory of Liver Disease Research the Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 51008China Department of Health Sciences College of Health SolutionsArizona State UniversityTempeUSA Guangdong Engineering&Technology Research Center for Gene Manipulation and Biomacromolecular Products Sun Yat-Sen UniversityGuangzhou 510080China Guangdong Province Key Laboratory of Diabetology Guangzhou 510o80China Guangdong Province Key Laboratory of Brain Function and Disease Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhou 510080China

Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide,and the development of nonalcoholic steatohepatitis(NASH)might cause irreversible hepatic damage.Hyperlipidemia(HLP)is the leading risk factor for NAFLD.This study aims to illuminate the causative contributor and potential mechanism of Kallistatin(KAL)mediating HLP to NAFLD.221 healthy control and 253 HLP subjects,62 healthy control and 44 NAFLD subjects were enrolled.The plasma KAL was significantly elevated in HLP subjects,especially in hypertriglyceridemia(HTG)subjects,and positively correlated with liver injury.Further,KAL levels of NAFLD patients were significantly up-regulated.KAL transgenic mice induced hepatic steatosis,inflammation,and fibrosis with time and accelerated inflammation development in high-fat diet(HFD)mice.In contrast,KAL knockout ameliorated steatosis and inflammation in high-fructose diet(HFruD)and methionine and choline-deficient(MCD)diet-induced NAFLD rats.Mechanistically,KAL induced hepatic steatosis and NASH by down-regulating adipose triglyceride lipase(ATGL)and comparative gene identification 58(CGl-58)by LRP6/Gas/PKA/GSK3βpathway through down-regulating peroxisome proliferator-activated receptor(PPARy)and up-regulating kruppel-like factor four(KLF4),respectively.CGl-58 is bound to NF-kB p65 in the cytoplasm,and diminishing CGl-58 facilitated p65 nuclear translocation and TNFa induction.Meanwhile,hepatic CGl-58-overexpress reverses NASH in KAL transgenic mice.Further,free fatty acids up-regulated KAL against thyroid hormone in hepatocytes.Moreover,Fenofibrate,one triglyceride-lowering drug,could reverse hepatic steatosis by down-regulating KAL.These results demonstrate that elevated KAL plays a crucial role in the development of HLP to NAFLD and may be served as a potential preventive and therapeutic target.

关键词： GSK3β inflammation elevated

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Perilipin 5 regulates hepatic stellate cell activation and high-fat diet-induced non-alcoholic fatty liver disease

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Animal Models and Experimental Medicine 2024年第2期7卷 166-178页

作者： Xuecui Yin Lin Dong Xiaohan Wang Zhenzhen Qin Yuying Ma Xiaofei Ke Ya Li Qingde Wang Yang Mi Quanjun Lyu Xia Xu Pengyuan Zheng Youcai Tang Department of Internal Medicine the Fifth Affiliated Hospital of Zhengzhou UniversityZhengzhouChina Department of Pediatrics the Fifth Affiliated Hospital of Zhengzhou UniversityZhengzhouChina Department of Clinical Nutrition the First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina Key Laboratory of Advanced Drug Preparation Technologies Ministry of Education of ChinaCo-innovation Center of Henan Province for New drug R&D and Preclinical SafetySchool of Pharmaceutical SciencesZhengzhou UniversityZhengzhouChina Department of Pediatrics GastroenterologyHenan Key Laboratory of Rehabilitation MedicineHenan Joint International Research Laboratory of Chronic Liver Injury and Henan Provincial Outstanding Overseas Scientists Chronic Liver Injury Studiothe Fifth Affiliated Hospital of Zhengzhou UniversityZhengzhouChina

Background:Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases globally.Hepatic stellate cells(HSCs)are the major effector cells of liver fibrosis.HSCs contain abundant lipid droplets(LDs)in their cytoplasm during quiescence.Perilipin 5(PLIN 5)is a LD surface-associated protein that plays a crucial role in lipid homeostasis.However,little is known about the role of PLIN 5 in HSC activation.Methods:PLIN 5 was overexpressed in HSCs of Sprague–Dawley rats by lentivirus transfection.At the same time,PLIN 5 gene knockout mice were constructed and fed with a high-fat diet(HFD)for 20 weeks to study the role of PLIN 5 in NAFLD.The corresponding reagent kits were used to measure TG,GSH,Caspase 3 activity,ATP level,and mitochondrial DNA copy number.Metabolomic analysis of mice liver tissue metabolism was performed based on UPLC-MS/MS.AMPK,mitochondrial function,cell proliferation,and apoptosis-related genes and proteins were detected by western blotting and qPCR.Results:Overexpression of PLIN 5 in activated HSCs led to a decrease in ATP levels in mitochondria,inhibition of cell proliferation,and a significant increase in cell apoptosis through AMPK activation.In addition,compared with the HFD-fed C57BL/6J mice,PLIN 5 knockout mice fed with HFD showed reduced liver fat deposition,decreased LD abundance and size,and reduced liver fibrosis.Conclusion:These findings highlight the unique regulatory role of PLIN 5 in HSCs and the role of PLIN 5 in the fibrosis process of NAFLD.

关键词： AMPK apoptosis hepatic stellate cell liver fibrosis perilipin 5

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Acidic/hypoxia dual-alleviated nanoregulators for enhanced treatment of tumor chemo-immunotherapy

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Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 136-152页

作者： Xiaoju Guo Xiaoxiao Chen Jiayi Ding Feng Zhang Shunyang Chen Xin Hu Shiji Fang Lin Shen Chenying Lu Zhongwei Zhao Jianfei Tu Gaofeng Shu Minjiang Chen Jiansong Ji Lishui Central hospital Shaoxing UniversityShaoxing 312000China Zhejiang Key Laboratory of Imaging and Interventional Medicine Imaging Diagnosis and Interventional Minimally Invasive InstituteThe Fifth Affiliated Hospital of Wenzhou Medical UniversityLishui 323000China Clinical College of The affiliated Central hospital School of MedicineLishui UniversityLishui 323000China Key Laboratory of Precision Medicine of Lishui Lishui 323000China

Chemotherapy plays a crucial role in triple-negative breast cancer (TNBC) treatment as it not only directly kills cancer cells but also induces immunogenic cell death. However, the chemotherapeutic efficacy was strongly restricted by the acidic and hypoxic tumor environment. Herein, we have successfully formulated PLGA-based nanoparticles concurrently loaded with doxorubicin (DOX), hemoglobin (Hb) and CaCO3 by a CaCO3-assisted emulsion method, aiming at the effective treatment of TNBC. We found that the obtained nanomedicine (DHCaNPs) exhibited effective drug encapsulation and pH-responsive drug release behavior. Moreover, DHCaNPs demonstrated robust capabilities in neutralizing protons and oxygen transport. Consequently, DHCaNPs could not only serve as oxygen nanoshuttles to attenuate tumor hypoxia but also neutralize the acidic tumor microenvironment (TME) by depleting lactic acid, thereby effectively overcoming the resistance to chemotherapy. Furthermore, DHCaNPs demonstrated a notable ability to enhance antitumor immune responses by increasing the frequency of tumor-infiltrating effector lymphocytes and reducing the frequency of various immune-suppressive cells, therefore exhibiting a superior efficacy in suppressing tumor growth and metastasis when combined with anti-PD-L1 (αPD-L1) immunotherapy. In summary, this study highlights that DHCaNPs could effectively attenuate the acidic and hypoxic TME, offering a promising strategy to figure out an enhanced chemo-immunotherapy to benefit TNBC patients.

关键词： CaCO3-based nanoparticles Hypoxia attenuation Acidity neutralization Reversal of chemotherapy resistance Enhanced chemo-immunotherapy

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Efficacy and safety of anlotinib combined with the STUPP regimen in patients with newly diagnosed glioblastoma: a multicenter, single-arm, phase Ⅱ trial

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Cancer Biology & Medicine 2024年第5期21卷 433-444页

作者： Shuzhen Lai Peijing Li Xiaohui Liu Guihong Liu Tieming Xie Xing Zhang Xiaoxuan Wang Jing Huang Yiqiang Tang Zhigang Liu Guoping Shen Chaoming Li Fangxiao Lu Lei Wang Fagui Jiang Caixing Sun Yuanyuan Chen Ming Chen Department of Radiotherapy Dongguan Institute of Clinical Cancer Research Dongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors Affiliated Dongguan Hospital Southern Medical University The Cancer Center The Fifth Affiliated Hospital of Sun Yat-Sen University Department of Radiation Oncology The First Affiliated Hospital of Sun Yat-Sen University Department of Oncology Maoming People's Hospital Department of Radiation Oncology Kecheng District People's Hospital Chinese Academy of Sciences Department of Radiation Oncology State Key Laboratory of Oncology in South China Sun Yat-sen University Cancer Center United Laboratory of Frontier Radiotherapy Technology of Sun Yat-sen university & Chinese Academy of Sciences Ion medical Technology Co. Ltd Department of Radiation Oncology The Second Affiliated Hospital of Soochow University Department of Radiation Oncology Yuebei People's Hospital Affiliated to the Medical College of Shantou University Chinese Academy of Sciences Department of Radiation Oncology The Second Clinical Medical College of Zhejiang Chinese Medical University Department of Radiation Oncology The Affiliated Hospital of Xuzhou Medical University Chinese Academy of Sciences State Key Laboratory of Translational Medicine and Innovative Drug Development Jiangsu Simcere Diagnostics Co. Ltd Department of Radiation Oncology The Affiliated Huai'an First People's Hospital of Nanjing Medical University Department of Radiation Oncology Jiangxi Cancer Hospital of Nanchang University

Objective: Glioblastomas are highly vascularized malignant tumors. We determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor, anlotinib, for a newly diagnosed glioblastoma.Methods: This multicenter, single-arm trial（NCT04119674） enrolled 33 treatment-na?ve patients with histologically proven glioblastomas between March 2019 and November 2020. Patients underwent treatment with the standard STUPP regimen [fractionated focal irradiation in daily fractions of 1.8-2 Gy given 5 d/w × 6 w（total = 54-60 Gy）] or radiotherapy plus continuous daily temozolomide（TMZ）(75 mg/m2of body surface area/d, 7 d/w from the first to the last day of radiotherapy), followed by 6 cycles of adjuvant TMZ（150±200 mg/m2× 5 d during each 28-d cycle） plus anlotinib(8 mg/d on d 1±14 of each 3-w cycle for 2 cycles during concomitant chemoradiotherapy, 8 maximal cycles as adjuvant therapy, followed by maintenance at 8 mg/d. The primary endpoint was progression-free survival（PFS）. Secondary endpoints included overall survival（OS） and adverse events（AEs）.Results: Thirty-three patients received the planned treatment. The median PFS was 10.9 months（95% CI, 9.9±18.7 months） and the 12-month PFS rate was 48.5%. The median OS was 17.4 months（95% CI, 14.5±21.1 months） and the 12-month OS rate was 81.8%. The most common AEs included hypertriglyceridemia [58%（n = 19）], hypoalbuminemia [46%（n = 15）], and hypercholesterolemia [46%（n = 15）] during concurrent chemoradiotherapy and leukopenia [73%（n = 24）], hypertriglyceridemia [67%（n = 22）], and neutropenia [52%（n = 17）] during adjuvant therapy. Five patients discontinued treatment due to AEs. HEG1（HR, 5.6; 95% CI, 1.3±23.7; P = 0.021） and RP1L1 alterations（HR, 11.1; 95% CI, 2.2±57.2; P = 0.004） were associated with a significantly shorter PFS.Conclusions: Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable toxicity. HEG1 and RP1L1 alterations might be novel predictive biomarkers of the response to anlotinib.

关键词： Glioblastoma anlotinib anti-angiogenesis multi-kinase inhibitor progression-free survival temozolomide

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Associations of sleeping patterns and isotemporal substitution of other behavior with the prevalence of CKD in Chinese adults

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Frontiers of Medicine 2024年第2期18卷 303-314页

作者： Yi Ding Xiaoli Xu Zhuojun Xin Qiuyu Cao Jiaojiao Huang Xianglin Wu Yanan Huo Qin Wan Yingfen Qin Ruying Hu Lixin Shi Qing Su Xuefeng Yu Li Yan Guijun Qin Xulei Tang Gang Chen Min Xu Tiange Wang Zhiyun Zhao Zhengnan Gao Guixia Wang Feixia Shen Zuojie Luo Li Chen Qiang Li Zhen Ye Yinfei Zhang Chao Liu Youmin Wang Tao Yang Huacong Deng Lulu Chen Tianshu Zeng Jiajun Zhao Yiming Mu Shengli Wu Yuhong Chen Jieli Lu Weiqing Wang Guang Ning Yu Xu Yufang Bi Mian Li Department of Endocrine and Metabolic Diseases Shanghai Institute of Endocrine and Metabolic DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China Shanghai National Clinical Research Center for Metabolic Diseases Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of ChinaShanghai Key Laboratory for Endocrine TumorState Key Laboratory of Medical GenomicsRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China Jiangxi Provincial People’s hospital Affiliated to Nanchang UniversityNanchang330000China Department of Endocrinology The Affiliated Hospital of Southwest Medical UniversityLuzhou646000China Department of Endocrinology The First Affiliated Hospital of Guangxi Medical UniversityNanning530000China Zhejiang Provincial Center for Disease Control and Prevention Hangzhou310000China Department of Endocrinology Affiliated Hospital of Guiyang Medical UniversityGuiyang550000China Xinhua hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200000China Tongji hospital Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430000China Sun Yat-sen Memorial hospital Sun Yat-sen UniversityGuangzhou510000China Department of Endocrinology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou450000China Department of Endocrinology The First Hospital of Lanzhou UniversityLanzhou730000China Fujian Provincial hospital Fujian Medical UniversityFuzhou350000China Dalian Municipal Central hospital Affiliated of Dalian Medical UniversityDalian116000China Department of Endocrinology The First Hospital of Jilin UniversityChangchun130000China Department of Endocrinology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou325000China Qilu hospital of Shandong university Jinan250000China Department of Endocrinology The Second Affiliated Hospital of Harbin Medical UniversityHarbin150000China Department of Endocrinology Cen

Studies have found a U-shaped relationship between sleep duration and chronic kidney disease(CKD)risk,but limited research evaluated the association of reallocating excessive sleep to other behavior with CKD.We included 104538 participants from the nationwide cohort of the Risk Evaluation of Cancers in Chinese Diabetic Individuals:A Longitudinal Study,with self-reported time of daily-life behavior.Using isotemporal substitution models,we found that substituting 1 h of sleeping with sitting,walking,or moderate-to-vigorous physical activity was associated with a lower CKD prevalence.Leisure-time physical activity displacement was associated with a greater prevalence reduction than occupational physical activity in working population.In stratified analysis,a lower CKD prevalence related to substitution toward physical activity was found in long sleepers.More pronounced correlations were observed in long sleepers with diabetes than in those with prediabetes,and they benefited from other behavior substitutions toward a more active way.The U-shaped association between sleep duration and CKD prevalence implied the potential effects of insufficient and excessive sleep on the kidneys,in which the pernicious link with oversleep could be reversed by time reallocation to physical activity.The divergence in the predicted effect on CKD following time reallocation to behavior of different domains and intensities and in subpopulations with diverse metabolic statuses underlined the importance of optimizing sleeping patterns and adjusting integral behavioral composition.

关键词： sleep physical activity chronic kidney disease isotemporal substitution behavioral pattern

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CHCHD2 Thr61Ile mutation impairs F1F0-ATPase assembly in in vitro and in vivo models of Parkinson's disease

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Neural Regeneration Research 2024年第1期19卷 196-204页

作者： Xiang Chen Yuwan Lin Zhiling Zhang Yuting Tang Panghai Ye Wei Dai Wenlong Zhang Hanqun Liu Guoyou Peng Shuxuan Huang Jiewen Qiu Wenyuan Guo Xiaoqin Zhu Zhuohua Wu Yaoyun Kuang Pingyi Xu Miaomiao Zhou Department of Neurology The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Department of Neurology The People’s Hospital of Guangxi Zhuang Autonomous RegionNanningGuangxi Zhuang Autonomous RegionChina School of Basic medical Sciences Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Department of Neurology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

Mitochondrial dysfunction is a significant pathological alte ration that occurs in Parkinson's disease(PD),and the Thr61lle(T61I)mutation in coiled-coil helix coiled-coil helix domain containing 2(CHCHD2),a crucial mitochondrial protein,has been reported to cause Parkinson's disease.FIFO-ATPase participates in the synthesis of cellular adenosine triphosphate(ATP)and plays a central role in mitochondrial energy metabolism.However,the specific roles of wild-type(WT)CHCHD2 and T611-mutant CHCHD2 in regulating F1FO-ATPase activity in Parkinson's disease,as well as whether CHCHD2 or CHCHD2 T61I affects mitochondrial function through regulating F1FO-ATPase activity,remain unclea r.Therefore,in this study,we expressed WT CHCHD2 and T61l-mutant CHCHD2 in an MPP^(+)-induced SH-SY5Y cell model of PD.We found that CHCHD2 protected mitochondria from developing MPP^(+)-induced dysfunction.Under normal conditions,ove rexpression of WT CHCHD2 promoted F1FO-ATPase assembly,while T61I-mutant CHCHD2 appeared to have lost the ability to regulate F1FO-ATPase assembly.In addition,mass spectrometry and immunoprecipitation showed that there was an interaction between CHCHD2 and F1FO-ATPase.Three weeks after transfection with AAV-CHCHD2 T61I,we intraperitoneally injected 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into mice to establish an animal model of chronic Parkinson's disease and found that exogenous expression of the mutant protein worsened the behavioral deficits and dopaminergic neurodegeneration seen in this model.These findings suggest that WT CHCHD2 can alleviate mitochondrial dysfunction in PD by maintaining F1F0-ATPase structure and function.

关键词： ATP synthase(F1F0-ATPase) coiled-coil helix coiled-coil helix domain containing 2 dopaminergic neuron mitochondrial dysfunction neurodegeneration oligomycin sensitivity-conferring protein Parkinson's disease T61I mutation tyrosine hydroxylase

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Engineered extracellular vesicles: A new approach for targeted therapy of tumors and overcoming drug resistance

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Cancer Communications 2024年第2期44卷 205-225页

作者： Chen Ming-Kun Chen Zi-Xian Cai Mao-Ping Chen Hong Chen Zhuang-Fei Zhao Shan-Chao Department of Urology The Third Affiliated Hospital of Southern Medical UniversityGuangzhouGuangdongP.R.China The Third Clinical College Southern Medical UniversityGuangzhouGuangdongP.R.China Luoyang Key Laboratory of Organic Functional Molecules College of Food and DrugLuoyang Normal UniversityLuoyangHenanP.R.China Department of Urology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdongP.R.China

Targeted delivery of anti-tumor drugs and overcoming drug resistance in malig-nant tumor cells remain significant clinical challenges.However,there are only few effective methods to address these issues.Extracellular vesicles(EVs),actively secreted by cells,play a crucial role in intercellular information transmis-sion and cargo transportation.Recent studies have demonstrated that engineered EVs can serve as drug delivery carriers and showed promising application prospects.Nevertheless,there is an urgent need for further improvements in the isolation and purification of EVs,surface modification techniques,drug assem-bly processes,and precise recognition of tumor cells for targeted drug delivery purposes.In this review,we summarize the applications of engineered EVs in cancer treatment and overcoming drug resistance,and current challenges asso-ciated with engineered EVs are also discussed.This review aims to provide new insights and potential directions for utilizing engineered EVs as targeted delivery systems for anti-tumor drugs and overcoming drug resistance in the near future.

关键词： drug delivery drug resistance extracellular vesicles nanoparticles

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Machine learning identifies the risk of complications after laparoscopic radical gastrectomy for gastric cancer

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World Journal of Gastroenterology 2024年第1期30卷 79-90页

作者： Qing-Qi Hong Su Yan Yong-Liang Zhao Lin Fan Li Yang Wen-Bin Zhang Hao Liu He-Xin Lin Jian Zhang Zhi-Jian Ye Xian Shen Li-Sheng Cai Guo-Wei Zhang Jia-Ming Zhu Gang Ji Jin-Ping Chen Wei Wang Zheng-Rong Li Jing-Tao Zhu Guo-Xin Li Jun You Department of Gastrointestinal Oncology Surgery The First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen 361001Fujian ProvinceChina Department of Gastrointestinal Surgery Qinghai University Affiliated HospitalXining 810000Qinghai ProvinceChina Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery The First Hospital Affiliated to Army Medical UniversityChongqing 400038China Department of General Surgery The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an 710061Shaanxi ProvinceChina Department of General Surgery The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029Jiangsu ProvinceChina Department of Gastrointestinal Surgery The First Affiliated Hospital of Xinjiang Medical UniversityUrmuqi 830054Xinjiang Uygur Autonomous RegionChina Department of General Surgery Nanfang HospitalSouthern Medical UniversityGuangzhou 510515Guangdong ProvinceChina Department of Gastrointestinal Surgery Affiliated Hangzhou First People's HospitalZhejiang University School of MedicineHangzhou 310006Zhejiang ProvinceChina Department of Gastrointestinal Surgery Zhongshan Hospital of Xiamen UniversityXiamen 361004Fujian ProvinceChina Department of Surgery The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical UniversityWenzhou 325027Zhejiang ProvinceChina Department of General Surgery Unit 4 Zhangzhou Affiliated Hospital of Fujian Medical UniversityZhangzhou 363000Fujian ProvinceChina Department of Gastrointestinal Surgery The Second Affiliated Hospital of Xiamen Medical CollegeXiamen 361021Fujian ProvinceChina Department of Gastrointestinal Nutrition and Hernia Surgery The Second Hospital of Jilin UniversityChangchun 130041Jilin ProvinceChina Department of Digestive Diseases Xijing HospitalAir Force Military Medical UniversityXi'an 710032Shaanxi ProvinceChina Department of Gastrointestinal Surgery Quanzhou First Hospital Affiliated to Fujian Medical UniversityQuanzhou 362002Fujian Provin

BACKGROUND Laparoscopic radical gastrectomy is widely used,and perioperative complications have become a highly concerned issue.AIM To develop a predictive model for complications in laparoscopic radical gastrectomy for gastric cancer to better predict the likelihood of complications in gastric cancer patients within 30 days after surgery,guide perioperative treatment strategies for gastric cancer patients,and prevent serious complications.METHODS In total,998 patients who underwent laparoscopic radical gastrectomy for gastric cancer at 16 Chinese medical centers were included in the training group for the complication model,and 398 patients were included in the validation group.The clinicopathological data and 30-d postoperative complications of gastric cancer patients were collected.Three machine learning methods,lasso regression,random forest,and artificial neural networks,were used to construct postoperative complication prediction models for laparoscopic distal gastrectomy and laparoscopic total gastrectomy,and their prediction efficacy and accuracy were evaluated.RESULTS The constructed complication model,particularly the random forest model,could better predict serious complications in gastric cancer patients undergoing laparoscopic radical gastrectomy.It exhibited stable performance in external validation and is worthy of further promotion in more centers.CONCLUSION Using the risk factors identified in multicenter datasets,highly sensitive risk prediction models for complications following laparoscopic radical gastrectomy were established.We hope to facilitate the diagnosis and treatment of preoperative and postoperative decision-making by using these models.

关键词： Gastric cancer Laparoscopic radical gastrectomy Postoperative complications Laparoscopic total gastrectomy

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Effect of novel accelerated intermittent theta burst stimulation on suicidal ideation in adolescent patients with major depressive episode:a randomised clinical trial

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General Psychiatry 2024年第2期37卷 292-296页

作者： Dong Huang Shuming Zhong Xiaodong Song Rongxu Zhang Shunkai Lai Yanbin Jia Department of Psychiatry First Affiliated Hospital of Jinan UniversityGuangzhouGuangdongChina

To the editor:Affective disorders,including major depressive disorder(MDD)and bipolar disorder,have emerged as the primary cause of adolescent suicide.Moreover,suicide mostly occurs in the major depressive episode(MDE)of affective disorders.Suicidal ideation(SI)has been identified as an immediate precursor to suicide,such that reducing its severity is conducive to suicide prevention in adolescents.

关键词： prevention editor stimulation

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