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Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis

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Neural Regeneration Research 2024年第6期19卷 1325-1335页

作者： Li Sun Zhaoyan Zhao Jing Guo Yuan Qin Qian Yu Xiaolong Shi Fei Guo Haiqin Zhang Xude Sun Changjun Gao Qian Yang department of Experimental Surgery The Second Affiliated Hospital of Air Force Medical University department of Anesthesiology The Second Affiliated Hospital of Air Force Medical University

Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury. Autologous mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion injury. Thus, transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic disease. To explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke, in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site(in situ). Animal behavior tests, immunofluorescence staining, 2,3,5-triphenyltetrazolium chloride(TTC) staining, mRNA-seq, and western blotting were used to assess mouse anxiety and memory, cortical infarct area, pyroptosis, and neurogenesis, respectively. Using bioinformatics analysis, western blotting, co-immunoprecipitation, and mass spectroscopy, we identified S100 calcium binding protein A9(S100A9) as a potential regulator of mitochondrial function and determined its possible interacting proteins. Interactions between exogenous and endogenous mitochondria, as well as the effect of exogenous mitochondria on recipient microglia, were assessed in vitro. Our data showed that:(1) mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function, as well as reducing infarct area, inhibiting pyroptosis, and promoting cortical neurogenesis;(2) microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function;(3) in vitro, exogenous mitochondria enhanced mitochondrial function, reduced redox stress, and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria; and(4) S100A9 promoted internalization of exogenous mitochondria by the microglia, thereby amplifying their pro-prolifera

关键词： ischemic stroke microglia mitochondria transplantation neurogenesis pyroptosis

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Immunoglobulin G-mediated food intolerance and metabolic syndrome influence the occurrence of reflux esophagitis in Helicobacter pylori-infected patients

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World Journal of Gastroenterology 2024年第8期30卷 855-862页

作者： Li-Hui Wang Bin-Bin Su Sheng-Shu Wang Guan-Chao Sun Kun-Ming Lv Yi Li Hui Shi Qian-Qian Chen College Chinese PLA General HospitalBeijing 100853China department of Gastroenterology Second Medical Center of Chinese PLA General HospitalBeijing 100853China Institute of Geriatrics The 2nd Medical CenterBeijing Key Laboratory of Aging and GeriatricsNational Clinical Research Center for Geriatrics DiseasesSecond Medical Center of Chinese PLA General HospitalBeijing 100853China department of Gastroenterology First Medical Center of Chinese PLA General HospitalBeijing 100853China

BACKGROUND Reflux esophagitis has an increasing prevalence and complex and diverse *** its risk factors is crucial to understanding the etiology,prevention,and management of the *** occurrence of reflux esophagitis may be associated with food reactions,Helicobacter pylori(***)infection,and metabolic *** To investigate the risk factors for reflux esophagitis and analyze the effects of immunoglobulin(Ig)G-mediated food intolerance,*** infection,and metabolic syndrome on reflux *** Outpatients attending the second medical Center of the pla General Hospital between 2017 and 2021 were retrospectively *** patients’basic information,test results,gastroscopy results,*** test results,and IgG-mediated food intolerance results were *** logistic regression analysis was used to analyze risk factors for reflux *** mediation analysis was used to evaluate the effects of IgG-mediated food intolerance and metabolic syndrome on *** infection affecting reflux *** A total of 7954 outpatients were included;the prevalence of reflux esophagitis,IgG-mediated food intolerance,*** infection,and metabolic syndrome were 20.84%,61.77%,35.91%,and 60.15%,*** analysis showed that the independent risk factors for reflux esophagitis included IgG-mediated food intolerance(OR=1.688,95%CI:1.497-1.903,P<0.00001)and metabolic syndrome(OR=1.165,95%CI:1.030-1.317,P=0.01484),and the independent protective factor for reflux esophagitis was *** infection(OR=0.400,95%CI:0.351-0.456,P<0.00001).IgG-mediated food intolerance had a partially positive mediating effect on *** infection as it was associated with reduced occurrence of reflux esophagitis(P=0.0200).Metabolic syndrome had a partially negative mediating effect on *** infection and reduced the occurrence of reflux esophagitis(P=0.0220).CONCLUSION Patients with IgG-mediated food intol

关键词： Gastroesophageal reflux Esophagitis Food intolerance Metabolic syndrome Helicobacter pylori Chemokines

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Chemoradiotherapy plus tislelizumab for mismatch repair proficient rectal cancer with supraclavicular lymph node metastasis:A case report

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2219-2224页

作者： Wen-Tao Zhong Yuan Lv Qian-Yu Wang Ran An Gang Chen Jun-Feng Du The second School of Clinical Medicine Southern Medical UniversityGuangzhou 510515Guangdong ProvinceChina department of General Surgery The 7^(th)Medical Center of PLA General HospitalBeijing 100700China department of Pathology The 7^(th)Medical Center of PLA General HospitalBeijing 100700China

BACKGROUND According to the latest report,colorectal cancer is still one of the most prevalent cancers,with the third highest incidence and mortality *** of advanced rectal cancer with distant metastases is usually unsatisfactory,especially for mismatch repair proficient(pMMR)rectal cancer,which leads to poor prognosis and *** SUMMARY We report a case of a pMMR rectal adenocarcinoma with metastases of multiple lymph nodes,including the left supraclavicular lymph node,before treatment in a 70-year-old *** received full courses of chemoradiotherapy(CRT)followed by 4 cycles of programmed death 1 inhibitor Tislelizumab,and a pathologic complete response(pCR)was achieved,and the lesion of the left supraclavicular lymph node also *** pMMR advanced rectal cancer with preserved intact distant metastatic lymph nodes may benefit from full-course CRT combined with immunotherapy.

关键词： Rectal cancer Metastasis Chemoradiotherapy Immunotherapy Prognosis Case report

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Development of a nomogram for predicting liver transplantation prognosis in hepatocellular carcinoma

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World Journal of Gastroenterology 2024年第21期30卷 2763-2776页

作者： Li He Wan-Sheng Ji Hai-Long Jin Wen-Jing Lu Yuan-Yuan Zhang Hua-Guang Wang Yu-Yu Liu Shuang Qiu Meng Xu Zi-Peng Lei Qian Zheng Xiao-Li Yang Qing Zhang department of Organ Transplantation The Third Medical Centre of Chinese PLA General HospitalBeijing 100039China School of Clinical Medicine Shandong Second Medical UniversityWeifang 261053Shandong ProvinceChina Clinical Research Center The Affiliated Hospital of Shandong Second Medical UniversityWeifang 261053Shandong ProvinceChina department of Laboratory Medicine The Third Medical Centre of Chinese PLA General HospitalBeijing 100039China Physiatry department Naval Aviation UniversityYantai 100071Shandong ProvinceChina

BACKGROUND At present,liver transplantation(LT)is one of the best treatments for hepatocellular carcinoma(HCC).Accurately predicting the survival status after LT can significantly improve the survival rate after LT,and ensure the best way to make rational use of liver *** To develop a model for predicting prognosis after LT in patients with *** Clinical data and follow-up information of 160 patients with HCC who underwent LT were collected and *** expression levels of alphafetoprotein(AFP),des-gamma-carboxy prothrombin,Golgi protein 73,cytokeratin-18 epitopes M30 and M65 were measured using a fully automated chemiluminescence *** best cutoff value of biomarkers was determined using the Youden *** regression analysis was used to identify the independent risk factors.A forest model was constructed using the random forest *** evaluated the accuracy of the nomogram using the area under the curve,using the calibration curve to assess consistency.A decision curve analysis(DCA)was used to evaluate the clinical utility of the *** The total tumor diameter(TTD),vascular invasion(VI),AFP,and cytokeratin-18 epitopes M30(CK18-M30)were identified as important risk factors for outcome after *** nomogram had a higher predictive accuracy than the Milan,university of California,San Francisco,and Hangzhou *** calibration curve analyses indicated a good *** survival and recurrence-free survival(RFS)of high-risk groups were significantly lower than those of low-and middle-risk groups(P<0.001).The DCA shows that the model has better clinical *** The study developed a predictive nomogram based on TTD,VI,AFP,and CK18-M30 that could accurately predict overall survival and RFS after *** can screen for patients with better postoperative prognosis,and improve longterm survival for LT patients.

关键词： Hepatocellular carcinoma Liver transplantation Liver cancer Nomogram Prognosis

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Predictive value of preoperative routine examination for the prognosis of patients with pT2N0M0 or pT3N0M0 colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2429-2438页

作者： Peng-Fei Jing Jin Chen En-Da Yu Chao-Yu Miao department of Colorectal Surgery Changhai HospitalSecond Military Medical University/Naval Medical UniversityShanghai 200433China department of Endocrinology and Metabolism Changhai HospitalSecond Military Medical University/Naval Medical UniversityShanghai 200433China department of Pharmacology Second Military Medical University/Naval Medical UniversityShanghai 200433China

BACKGROUND In recent years,the incidence of colorectal cancer(CRC)has been *** the popularization of endoscopic technology,a number of early CRC has been ***,despite current treatment methods,some patients with early CRC still experience postoperative recurrence and *** To search for indicators associated with early CRC recurrence and metastasis to identify high-risk *** A total of 513 patients with pT2N0M0 or pT3N0M0 CRC were retrospectively enrolled in this *** of blood routine test,liver and kidney function tests and tumor markers were collected before *** were followed up through disease-specific database and telephone *** recurrence,metastasis or death were used as the end point of study to find the risk factors and predictive value related to early CRC recurrence and *** We comprehensively compared the predictive value of preoperative blood routine,blood biochemistry and tumor markers for disease-free survival(DFS)and overall survival(OS)of *** multivariate analysis demonstrated that low platelet count was significantly associated with poor DFS[hazard ratio(HR)=0.995,95% confidence interval(CI):0.991-0.999,P=0.015],while serum carcinoembryonic antigen(CEA)level(HR=1.008,95%CI:1.001-1.016,P=0.027)and serum total cholesterol level(HR=1.538,95%CI:1.026-2.305,P=0.037)were independent risk factors for *** cutoff value of serum CEA level for predicting OS was 2.74 ng/*** the OS of CRC patients with serum CEA higher than the cutoff value was worse than those with lower CEA level,the difference between the two groups was not statistically significant(P=0.075).CONCLUSION For patients with T2N0M0 or T3N0M0 CRC,preoperative platelet count was a protective factor for DFS,while serum CEA level was an independent risk factor for *** that these measures are easier to detect and more acceptable to patients,they may have broader applications.

关键词： Colorectal cancer platelet count Serum carcinoembryonic antigen Total cholesterol level Overall survival Disease-free survival

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New roles of tumor-derived exosomes in tumor microenvironment

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Chinese Journal of Cancer Research 2024年第2期36卷 151-166页

作者： Shiqian Chen Jinzhe Sun Huan Zhou Hongbin Lei Dan Zang Jun Chen department of Oncology the Second Hospital of Dalian Medical UniversityDalian 116023China department of Radiotherapy the Second Hospital of Dalian Medical UniversityDalian 116023China

Throughout tumorigenesis, the co-evolution of tumor cells and their surrounding microenvironment leads to the development of malignant phenotypes. Cellular communication within the tumor microenvironment(TME) plays a critical role in influencing various aspects of tumor progression, including invasion and metastasis. The release of exosomes, a type of extracellular vesicle, by most cell types in the body, is an essential mediator of intercellular communication. A growing body of research indicates that tumor-derived exosomes(TDEs) significantly expedite tumor progression through multiple mechanisms, inducing epithelial-mesenchymal transition and macrophage polarization, enhancing angiogenesis, and aiding in the immune evasion of tumor cells. Herein, we describe the formation and characteristics of the TME, and summarize the contents of TDEs and their diverse functions in modulating tumor development. Furthermore, we explore potential applications of TDEs in tumor diagnosis and treatment.

关键词： Tumor-derived exosomes tumorigenesis tumor microenvironment diagnosis treatment

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Causal relationship between feelings and cognitive decline:An univariable and multivariable Mendelian randomization study

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World Journal of Psychiatry 2024年第3期14卷 421-433页

作者： Juan Liu Lin Liu Yi-Xin Hu Jian-Hua Li Xiao Zou Hao-Yun Zhang Li Fan department of Cardiology The Second Medical Center&National Clinical Research Center for Geriatric DiseasesChinese PLA General HospitalBeijing 100853China department of Pulmonary and Critical Care Medicine The Second Medical Center&National Clinical Research Center for Geriatric DiseasesChinese PLA General HospitalBeijing 100853China The Fourth department of Geriatric Health Care The Second Medical Center&National Clinical Research Center for Geriatric DiseasesChinese PLA General HospitalBeijing 100853China department of Anesthesiology First Medical Center of Chinese PLA General HospitalBeijing 100853China

BACKGROUND While the impact of depression on cognition is well-documented,the relationship between feelings and cognition has received limited *** To explore the potential association between feelings and cognition with a twosample Mendelian randomization(MR)*** Our analysis utilized genome-wide association data on various feelings(fed-up feelings,n=453071;worrier/anxious feelings,n=450765;guilty feelings,n=45-0704;nervous feelings,n=450700;sensitivity/hurt feelings,n=449419;miserableness,n=454982;loneliness/isolation,n=455364;happiness,n=152348)in the European population and their impact on cognitive functions(intelligence,n=269867).Conducting a univariable MR(UVMR)analysis to assess the relationship between feelings and *** this analysis,we applied the inverse variance weighting(IVW),weighted median,and MR Egger ***,we performed sensitivity analysis(leave-one-out analysis),assessed heterogeneity(using MR-PRESSO and Cochran’s Q test),and conducted multiple validity test(employing MR-Egger regression).Subsequently,a multivariable MR(MVMR)analysis was employed to examine the impact of feelings on *** served as the primary method in the multivariable analysis,complemented by median-based and MR-Egger *** In this study,UVMR indicated that sensitivity/hurt feelings may have a negative causal effect on cognition(OR=0.63,95%CI:0.43-0.92,P=0.017).After adjustment of other feelings using MVMR,a direct adverse causal effect on cognition was observed(OR_(MVMR)=0.39,95%CI:0.17-0.90,P_(MVMR)=0.027).While a potential increased risk of cognitive decline was observed for fed-up feelings in the UVMR analysis(ORUVMR=0.64,95%CI:0.42-0.97,PUVMR=0.037),this effect disappeared after adjusting for other feelings(OR_(MVMR)=1.42,95%CI:0.43-4.74,P_(MVMR)=0.569).These findings were generally consistent across MV-IVW,median-based,and MR-Egger ***-Egger regression revealed pleiotropy in the impact of worrier/anxious

关键词： Mendelian randomization analysis Feelings Cognition Intelligence

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In vivo imaging of the neuronal response to spinal cord injury:a narrative review

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Neural Regeneration Research 2024年第4期19卷 811-817页

作者： Junhao Deng Chang Sun Ying Zheng Jianpeng Gao Xiang Cui Yu Wang Licheng Zhang Peifu Tang department of Orthopedics The Fourth Medical Center of Chinese PLA General Hospital National Clinical Research Center for Orthopedics Sports Medicine and Rehabilitation School of Life Sciences Tsinghua University department of Orthopedics Air Force Medical CenterPLA medical School of Chinese pla Institute of Orthopedics The First Medical CenterChinese PLA General Hospital Key Lab of Regenerative Medicine in Orthopedics Key Laboratory of Musculoskeletal Trauma and War Injuries PLA

Deciphering the neuronal response to injury in the spinal cord is essential for exploring treatment strategies for spinal cord injury(SCI).However,this subject has been neglected in part because appropriate tools are *** in vivo imaging and labeling methods offer great potential for observing dynamic neural processes in the central nervous system in conditions of health and *** review first discusses in vivo imaging of the mouse spinal cord with a focus on the latest imaging techniques,and then analyzes the dynamic biological response of spinal cord sensory and motor neurons to *** then summarize and compare the techniques behind these studies and clarify the advantages of in vivo imaging compared with traditional neuroscience ***,we identify the challenges and possible solutions for spinal cord neuron imaging.

关键词： anterior horn neurons calcium imaging central nervous system dorsal horn neurons dorsal root ganglion in vivo imaging neuronal response spinal cord injury spinal cord two-photon microscopy

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Identifying Comprehensive Genomic Alterations and Potential Neoantigens for Cervical Cancer Immunotherapy in a Cohort of Chinese Squamous Cell Carcinoma of the Cervix

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Biomedical and Environmental Sciences 2024年第6期37卷 565-580页

作者： Meng Wu Jialu Zhou Zhe Zhang Yuanguang Meng School of Medicine Nankai UniversityTianjin 300071China department of Obstetrics and Gynecology The First Medical Center of Chinese PLA General HospitalBeijing 100853China department of Obstetrics and Gynecology Chinese PLA Medical SchoolBeijing 100853China department of Obstetrics and Gynecology The Seventh Medical Center of Chinese PLA General HospitalBeijing 100700China

Objective Genomic alterations and potential neoantigens for cervical cancer immunotherapy were identified in a cohort of Chinese patients with cervical squamous cell carcinoma(CSCC).Methods Whole-exome sequencing was used to identify genomic alterations and potential neoantigens for CSCC *** Sequencing was performed to analyze neoantigen *** Systematic bioinformatics analysis showed that C>T/G>A transitions/transversions were dominant in *** mutations were the most frequent types of somatic mutation in the coding sequence *** signature analysis detected signature 2,signature 6,and signature 7 in CSCC ***3CA,FBXW7,and BICRA were identified as potential driver genes,with BICRA as a newly reported *** variation profiling identified 4,960 potential neoantigens,of which 114 were listed in two neoantigen-related *** The present findings contribute to our understanding of the genomic characteristics of CSCC and provide a foundation for the development of new biotechnology methods for individualized immunotherapy in CSCC.

关键词： Cervical squamous cell carcinoma Genome alteration Neoantigens Immunotherapy

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Alterations in expression and localization of POMGNT1 in the APP/PS1 mouse model of Alzheimer’s disease

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Genes & Diseases 2024年第5期11卷 55-58页

作者： Hanxiao Jiang Yuxue Feng Xia Hao Guiqiong He Xiaofeng Li department of Neurology The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 401336China Chongqing Key Laboratory of Neurobiology Chongqing Medical UniversityChongqing 400016China department of anatomy Chongqing Medical UniversityChongqing 400016China department of Neurology The Fifth People’s Hospital of ChongqingChongqing 400062China

Alzheimer’s disease(AD)is a complex and progressive neurodegenerative disorder that causes dementia in the aging *** of the characteristic pathologic hallmarks of AD is the senile plaques,composed of the accumulation of *** b-amyloid results from the cleavage of transmembrane b-amyloid precursor protein(APP)by b-secretases and g-secretases,sequentially.O-mannosylation was found essential for the normal function of APP in Saccharomyces cerevisiae.1 Protein Olinked mannose b1,2-N-acetyl-glucosaminyltransferase 1(POMGNT1)is a glycosyltransferase crucial for the elongation of O-mannosyl glycans and catalyzes the transfer of Nacetylglucosamine from uridine 50-diphosphate-N-acetylglucosamine to O-mannose of glycoproteins.

关键词： APP/PS1 Alzheimer amyloid

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