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Intranasal adenovirus-vectored Omicron vaccine induced nasal immunoglobulin A has superior neutralizing potency than serum antibodies

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3507-3518页

作者： Si Chen Zhengyuan Zhang Qian Wang Qi Yang Li Yin Lishan Ning Zhilong Chen Jielin Tang Weiqi Deng Ping He Hengchun Li Linjing Shi yjun Deng Zijian Liu Hemeng Bu Yaohui Zhu Wenming Liu Linbing Qu Ligiang Feng Xiaoli Xiong Baoqing Sun Nanshan Zhong Feng Li ingchao Li Xinwen Chen Ling Chen guangzhou Institute of Infectious Disease Guangzhou Eighth People's HospitalGuangzhou Medical UniversityGuangzhouChina guangzhou National Laboratory GuangzhouChina State Key Laboratory of Respiratory Disease Center for Cell Lineage ResearchGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouChina University of Chinese Academy of Sciences BeijingChina State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina Xiamen United Institute of Respiratory Health XiamenChina

The upper respiratory tract is the initial site of SARS-CoV-2 *** spike-specific secretory immunoglobulin A(slgA)correlates with protection against Omicron breakthrough *** report that intranasal vaccination using human adenovirus serotype 5(Ad5)vectored Omicron spike in people who previously vaccinated with ancestral vaccine could induce robust neutralizing slgA in the nasal *** slgA was predominantly present in dimeric and multimeric forms and accounted for nearly 40%of total proteins in nasal mucosal lining fluids(NMLFs).A low-level IgG could also be detected in NMLFs but not IgM,IgD,and *** a complete nasal wash,slgA in the nasal passage could be replenished rapidly within a few hours.A comparison of purified paired serum IgA,serum IgG,and nasal slgA from the same individuals showed that slgA was up to 3-logs more potent than serum antibodies in binding to spikes and in neutralizing Omicron *** IgG and IgA failed to neutralize XBB and BA.2.86,while nasal slgA retained potent neutralization against these newly emerged *** analysis showed that slgA Was more effective than IgG or IgA in blocking spike-mediated cell-to-cell transmission and protecting hACE2 mice from XBB *** a slgA monoclonal antibody as a reference,we estimated that the total nasal slgA contains about 2.6-3.9%spikespecific slgA in NMLFs collected approximately one month after intranasal *** study provided insights for developing intranasal vaccines that can induce slgA to build an effective and mutation-resistant first-line immune barrier against constantly emerging variants.

关键词： nasal antibodies neutral

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The Correlation between Free Triiodothyronine, Free Thyroxine and Hypertension in Depression Patients with Hypothyroidism and Its Clinical Guiding Value

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Journal of Biosciences and Medicines 2024年第6期12卷 191-201页

作者： Jingxuan Liu Fang Wang Xinhua Zhou College of Pharmacy Jinan University Guangzhou China Department of Neurology Wuxue First Peoples Hospital Wuxue China guangzhou eighth peoples hospital Guangzhou Medical University Guangzhou China

Background: Cardiovascular diseases, such as hypertension and coronary heart disease, are often accompanied by thyroid and mental diseases, the harm of which poses great threats to patients’ health. Objective: To explore the correlation between free triiodothyronine (FT3), free thyroxine (FT4) and hypertension in depression patients with hypothyroidism and its clinical guiding value. Methods: A total of 548 patients diagnosed with hypothyroidism in Wuxue First People’s hospital of Hubei Province from January 2018 to September 2022 were enrolled. According to whether complicated with depression, they were divided into hypothyroidism without depression group (group A) and hypothyroidism with depression group (group B). The gender, age, comorbidities (such as depression, hypertension, diabetes, dyslipidemia, acute myocardial infarction), FT3, FT4, and thyroid stimulating hormone (TSH) levels were recorded. Spearman rank correlation was used to analyze hypertensive patients with hypothyroidism. Multivariate binary Logistic regression was used to analyze the influencing factors of hypertension in patients with hypothyroidism. Results: The TSH level, the number of hypertension, coronary heart disease and hyperlipidemia in group B were statistically significantly higher than those in group A (P 3 level in group B was statistically significantly lower than that in group A (P s = 0.092), coronary heart disease (rs = 0.000), hyperlipidemia (rs = 0.000), diabetes (rs = 0.000), and age (rs = 0.000), and negatively correlated with FT3 (rs = 0.000) (P 3 and FT4 were the influencing factors of hypertension. The risk of hypertension in patients with coronary heart disease and hyperlipidemia significantly increased by 3.425 and 1.761 times (P 3, the risk of hypertension increased (P 4, the risk of hypertension significantly increased (P 3 and FT4 are the influencing factors of hypertension. The lower the FT3 level, the higher the FT4 level, the higher the risk of hypertension. FT3 a

关键词： Hypothyroidism Depression Hypertension Coronary Heart Disease Correlation Analysis FT3 FT4

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Hierarchical learning of gastric cancer molecular subtypes by integrating multi-modal DNA-level omics data and clinical stratification

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Quantitative Biology 2024年第2期12卷 182-196页

作者： Binyu Yang Siying Liu Jiemin Xie Xi Tang Pan Guan Yifan Zhu Xuemei Liu Yunhui Xiong Zuli Yang Weiyao Li Yonghua Wang Wen Chen Qingjiao Li Li C.Xia Department of Statistics and Financial Mathematics School of MathematicsSouth China University of TechnologyGuangzhouChina School of Physics and Optoelectronics South China University of TechnologyGuangzhouChina Department of Pathology The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouChina School of Food Science and Engineering South China University of TechnologyGuangzhouChina Department of Laboratory Medicine the Eighth Affiliated HospitalSun Yat-sen UniversityShenzhenChina

Molecular subtyping of gastric cancer(GC)aims to comprehend its genetic ***,the efficacy of current subtyping methods is hampered by their mixed use of molecular features,a lack of strategy optimization,and the limited availability of public GC *** is a pressing need for a precise and easily adoptable subtyping approach for early DNA-based screening and *** on TCGA subtypes,we developed a novel DNA-based hierarchical classifier for gastric cancer molecular subtyping(HCG),which employs gene mutations,copy number aberrations,and methylation patterns as *** incorporating the closely related esophageal adenocarcinomas dataset,we expanded the TCGA GC dataset for the training and testing of HCG(n=453).The optimization of HCG was achieved through three hierarchical strategies using Lasso-Logistic regression,evaluated by their overall the area under receiver operating characteristic curve(auROC),accuracy,F1 score,the area under precision-recall curve(auPRC)and their capability for clinical stratification using multivariate survival ***-specific DNA alteration biomarkers were discerned through difference tests based on HCG defined *** HCG classifier demonstrated superior performance in terms of overall auROC(0.95),accuracy(0.88),F1 score(0.87)and auPRC(0.86),significantly improving the clinical stratification of patients(overall p-value=0.032).Difference tests identified 25 subtype-specific DNA alterations,including a high mutation rate in the SYNE1,ITGB4,and COL22A1 genes for the MSI subtype,and hypermethylation of ALS2CL,KIAA0406,and RPRD1B genes for the EBV *** is an accurate and robust classifier for DNA-based GC molecular subtyping with highly predictive clinical stratification *** training and test datasets,along with the analysis programs of HCG,are accessible on the GitHub website(***/LabxSCUT).

关键词： DNA alterations gastric cancer hierarchical classification molecular subtyping multi-omics

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Acceptance and Factors Associated With Participation in Functional Cure–Related Trials Among People Living With HIV: A Cross-sectional Study in Southern China

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Infectious Microbes & Diseases 2024年第1期6卷 11-19页

作者： Zhaomin Deng Minjuan Shi Yue Yuan GuangjinCao Chunyan Wen Lijuan Chen Xueying Fan Linan Wu Jianhui Yuan Huachun Zou Linghua Li Caijun Sun School of Public Health(Shenzhen) Shenzhen Campus of Sun Yat-sen UniversityShenzhenChina Department of Diseases Control Panyu District Center for Disease Control and PreventionGuangzhouChina Infectious Disease Center Guangzhou Eighth People's HospitalGuangzhou Medical UniversityGuangzhouChina Nanshan District Center for Disease Control and Prevention ShenzhenChina Key Laboratory of Tropical Disease Control(Sun Yat-sen University) Ministry of EducationGuangzhouChina

HIV remains a global health challenge,and research efforts directed towards a functional cure require people living with HIV(PLHIV)in-volvement in clinical *** study assessed willingness to participate in HIV functional cure–related clinical trials and associated factors among PLHIV in guangzhou,China,using a questionnaire survey *** analyzed responses from 718 questionnaires,finding that 71.2%were willing to participate in Phase Ⅲtrials,while 51.7%were willing to participate in Phase I trials and 42.9%expressed acceptability for analytic treatment *** logistic regression demonstrated that male PLHIV,those with awareness of functional cure,and PLHIV,who had been on antiretroviral therapy(ART)for less than 1 year,were more willing to partic-ipate in Phase Ⅲ*** with a body mass index greater than 24,and those without resistance to ART drug were more willing to participate in Phase I *** major motivations for participation in Phase Ⅲtrials were access to cutting-edge treatments(62.6%)and supporting research(55.3%).Safety was the main concern contributing to *** study revealed a high willingness to participate in HIV functional cure–related trials among PLHIV in guangzhou,China,and willingness varied across different trial phases and was influenced by multiple *** study provides valuable references for future clinical trial recruitment strategies and public health policy formulation.

关键词： people living with HIV functional cure clinical trials willingness

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Combination of manual lymphatic drainage and Kinesio taping for treating pigmented villonodular synovitis:A case report

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World Journal of Clinical Cases 2024年第19期12卷 3971-3977页

作者： Yan-Ping Qu Wei Jin Ben Huang Jie Shen Department of Rehabilitation Medicine Shanghai Eighth Peoples HospitalShanghai 200235China

BACKGROUND Pigmented villonodular synovitis(PVNS)is a benign proliferative disorder that affects the synovial joints,bursae,and tendon *** date,few studies have reported on the treatment of postoperative pain and edema in patients with ***,we present the case of a woman who developed pain and edema in the left lower limb 1 wk after synovectomy and arthroscopic partial meniscectomy and was unable to walk due to limited flexion and extension of the left *** SUMMARY A 32-year-old woman underwent synovectomy and arthroscopic partial meniscectomy successively and was treated with a combination of manual lymphatic drainage(MLD)and kinesio taping(KT)in our hospital to alleviate postoperative pain and *** following parameters were assessed at 2 wk post-treatment and 1 wk post-discharge follow up:suprapatellar circumference,infrapatellar circumference,visual analog scale score,knee range of motion,pittsburgh sleep quality index score,hamilton anxiety rating scale(HAMA)score,and hamilton depression rating scale(HAMD)*** treatment,the postoperative pain and edema in the patient’s left knee were effectively relieved,resulting in improved sleep quality and remarkably attenuated HAMA and HAMD *** Combined MLD and KT may be an effective approach for relieving postoperative pain and edema in patients with PVNS.

关键词： Pigmented villonodular synovitis Manual lymphatic drainage Kinesio taping Postoperative pain Edema Case report

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Cancer immunotherapy with envelopedself-amplifying mRNA CARG-2020 thatmodulates IL-12,IL-17 and PD-L1 pathways toprevent tumor recurrence

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Acta Pharmaceutica Sinica B 2024年第1期14卷 335-349页

作者： Ju Chen Bhaskara Reddy Madina Elham Ahmadi Timur Olegovich Yarovinsky Marie Marthe Krady Eileen Victoria Meehan Isabella China Wang Xiaoyang Ye Elise Pitmon Xian-Yong Ma Bijan Almassian Valerian Nakaar Kepeng Wang Department of Immunology School of MedicineUniversity of Connecticut Health CenterFarmingtonCT 06030USA CaroGen Corporation FarmingtonCT 06030USA The eighth Clinical Medical College of guangzhou University of Chinese Medicine Foshan Hospital of Traditional Chinese MedicineFoshan 528000China The Loomis Chaffee School WindsorCT 06095USA

Targeting multiple immune mechanisms may overcome therapy resistance and further improve cancer immunotherapy for ***,we describe the application of virus-like vesicles(VLV)for delivery of three immunomodulators alone and in combination,as a promising approach for cancer *** vectors were designed to deliver single chain interleukin(IL)-12,shorthairpin RNA(shRNA)targeting programmed death ligand 1(PD-L1),and a dominant-negative form of IL-17 receptor A(dn-IL17RA)as a single payload or as a combination *** delivery of the VLV vector expressing IL-12 alone,as well as the trivalent vector(designated CARG-2020)eradicated large established ***,only CARG-2020 prevented tumor recurrence and provided long-term survival benefit to the tumor-bearing mice,indicating a benefit of the combined *** abscopal effects of CARG-2020 on the non-injected contralateral tumors,as well as protection from the tumor cell re-challenge,suggest immune-mediated mechanism of protection and establishment of immunological ***,CARG-2020 potently activates Th1 immune mechanisms and inhibits expression of genes related to T cell exhaustion and cancer-promoting *** ability of CARG-2020 to prevent tumor recurrence and to provide survival benefit makes it a promising candidate for its development for human cancer immunotherapy.

关键词： Virus-like vesicles Oncolytic virus IL-12 IL-17 PD-L1 T cell exhaustion Combination therapy Cancer immunotherapy

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Flux Balance Analysis Reveals Potential Anti-HIV-1 Metabolic Targets

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Infectious Diseases & Immunity 2024年第2期4卷 61-68页

作者： Runpeng Han Fei Luo Haisheng Yu Yajun Yan Yan Gong Conghua Xie Liang Cheng Department of Radiation and Medical Oncology Medical Research InstituteZhongnan Hospital of Wuhan UniversityWuhan UniversityWuhan 430071China Frontier Science Center for Immunology and Metabolism Zhongnan Hospital of Wuhan UniversityState Key Laboratory of VirologyWuhan UniversityWuhan 430071China guangzhou eighth People's hospital Guangzhou Medical UniversityGuangzhou 510440China Department of Infectious Diseases Zhongnan Hospital of Wuhan UniversityWuhan 430071China Department of Biological Repositories Zhongnan Hospital of Wuhan UniversityWuhan 430071China Wuhan Research Center for Infectious Diseases and Cancer Chinese Academy of Medical SciencesWuhan 430071China

Background:Human immunodeficiency virus type 1(HIV-1)remains a persistent global health ***,a continuous exploration of novel therapeutic strategies is essential.A comprehensive understanding of how HIV-1 utilizes the cellular metabolism machinery for replication can provide insights into new therapeutic ***:In this study,we performed a flux balance analysis using a genome-scale metabolic model(GEM)integrated with an HIV-1 viral biomass objective function to identify potential targets for anti–HIV-1 *** generated a GEM by integrating an HIV-1 production reaction into CD4+T cells and optimized for both host and virus optimal states as objective functions to depict metabolic profiles of cells in the status for optimal host biomass maintenance or for optimal HIV-1 virion *** analysis was used to predict biochemical reactions altered optimal for HIV-1 *** addition,we conducted in silico simulations involving gene and reaction knock-outs to identify potential anti–HIV-1 targets,which were subsequently validated by human phytohemagglutinin(PHA)blasts infected with ***:Differential analysis identified several altered biochemical reactions,including increased lysine uptake and oxidative phosphorylation(OXPHOS)activities in the virus optima compared with the host *** silico gene and reaction knock-out simulations revealed de novo pyrimidine synthesis,and OXPHOS could serve as potential anti–HIV-1 metabolic *** vitro assay confirmed that targeting OXPHOS using metformin could suppress the replication of HIV-1 by 56.6%(385.4±67.5 pg/mL in the metformintreated group vs.888.4±32.3 pg/mL in the control group,P<0.001).Conclusion:Our integrated host-virus genome-scale metabolic study provides insights on potential targets(OXPHOS)for anti-HIV therapies.

关键词： HIV-1 Flux balance analysis Genome-scale metabolic models Viral biomass objective function Therapeutic target

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Clinical efficacy and gene chip expression analysis of Shenzhu Guanxin recipe granules(参术冠心方颗粒) in patients with intermediate coronary lesions

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Journal of Traditional Chinese Medicine 2024年第3期44卷 545-553页

作者： JIN Xiao WU Bingxin LIN Miaoyang ZHONG Biying LIN Luoqi XU Danping Department of Traditional Chinese Medicine the First Affiliated Hospital of Jinan UniversityJinan UniversityGuangzhou 510630.510630China Department of Cardiology Second Clinical College of Guangzhou University of Chinese MedicineGuangzhou 510000China Department of Traditional Chinese Medicine the Eighth Affiliated HospitalSun Yat-Sen UniversityShenzhen 518033China

OBJECTIVE: To evaluate the clinical efficacy and safety of Shenzhu Guanxin recipe granules(参术冠心颗粒, SGR) in treating patients with intermediate coronary lesions(ICL), and to investigate the potential mechanism though a transcriptome sequencing approach. METHODS: ICL patients with Qi deficiency and phlegm stasis were adopted and randomly assigned to a case group or a control by random number generator in a 1∶1 randomization ratio to evaluate the clinical efficacy. RESULTS: There was no significant difference between the two groups in coronary computed tomography angiography related indexes in the two groups before and after intervention. Through the gene chip expression analysis, it is finally concluded that there are 355 differential mRNAs(190 up-regulated genes and 165 down regulated genes) when compared the SGR group and placebo group. Through protein-protein interaction network analysis of differentially expressed genes, 10 hub genes were finally obtained: CACNA2D2, CACNA2D3, DNAJC6, FGF12, SGSM2, CACNA1G, LRP6, KIF25, OXTR, UPB1. CONCLUSIONS: SGR combined with Western Medicine can be safely used to treat ICL patients with Qi deficiency and phlegm stasis. The possible mechanism of action and relevant gene loci and pathway were proposed.

关键词： intermediate coronary lesions gene expression profiling Qi deficiency and phlegm stasis Shenzhu Guanxin recipe granules

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Prevalence of bacteria, fungi, and virus coinfections with SARS-CoV-2 Omicron variant among patients with severe COVID-19 in guangzhou, China, winter 2022

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Biosafety and Health 2024年第2期6卷 92-97页

作者： Qinghong Fan Mengling Jiang Jun Zhang Guofang Tang Ming Gao Yingfen Wen Xizi Deng Jun Dai Honghao Lai Peng Qian Yaqing Lin Ruiying He Liya Li Yueping Li Zhengtu Li Xuesong Liu Yimin Li Na Yu Yun Lan Fengyu Hu Feng Li Institute of Infectious Diseases Guangzhou Eighth People's HospitalGuangzhou Medical UniversityGuangzhou 510440China State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of GuangzhouMedicalUniversityGuangzhou510120China guangzhou Laboratory Guangzhou 510700China

The status of coinfection during the national outbreak of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron BA.5.2 or BF.7 in China in the winter of 2022,which is suspected to contribute substantially to the overloaded severe cases,needs to be *** analyzed the coinfection status of 385 severe patients infected with the Omicron variant in guangzhou using metagenomic *** found that 317(82.3%)patients were coinfected with at least one additional pathogen(s),including bacteria(58.7%),fungi(27.1%)and viruses(73.5%).Pseudomonas aeruginosa(***)(24.2%),Staphylococcus aureus(***)(14.0%),andKlebsiella pneumoniae(***)(13.4%)ranked as the top three coinfected *** fumigatus(***)(39.5%),Pneumocystis jirovecii(***)(24.4%)andCanidia albicans(***)(22.1%)were the top three coinfected ***-Barr virus(EBV)(63.1%),Human herpesvirus 7(HHV-7)(34.8%),and Herpes simplex virus 1(HSV-1)(32.6%)were the top three coinfected *** note,the detection of multiple coinfections of potential pathogenic bacteria,fungi,and viruses,despite lacking consistent patterns,highlighted a complicated synergistic contribution to disease *** study presents the most comprehensive spectrum of bacterial,fungal,and viral coinfections in Omicron-associated severe coronavirus disease 2019(COVID-19),implying that the coinfection of conditional pathogens might synergistically deteriorate the Omicron infection outcomes.

关键词： SARS-CoV-2 Omicron BA.5.2 Omicron BF.7 Coinfection Severeinfection

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Comparison efficacy and safety of total laparoscopic gastrectomy and laparoscopically assisted total gastrectomy in treatment of gastric cancer

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World Journal of Gastrointestinal Surgery 2024年第6期16卷 1871-1882页

作者： Long Li Dong-Yuan Liu Jing Leng Xue-Mei Tao Hui-Qin Wu Yan-Peng Zhu Department of General Surgery The 971^(st)Hospital of Chinese People's Liberation ArmyQingdao 266071Shandong ProvinceChina Department of Surgery Qingdao Municipal HospitalQingdao 266071Shandong ProvinceChina Hyperbaric Oxygen Department The Eighth Peoples Hospital of QingdaoQingdao 266121Shandong ProvinceChina Department of Gastrointestinal Surgery The First Affiliated Hospital of Naval Medical UniversityShanghai 200433China

BACKGROUND The development of laparoscopic technology has provided a new choice for surgery of gastric cancer(GC),but the advantages and disadvantages of laparoscopic total gastrectomy(LTG)and laparoscopic-assisted total gastrectomy(LATG)in treatment effect and safety are still *** purpose of this study is to compare the efficacy and safety of the two methods in the treatment of GC,and to provide a basis for clinical *** To compare the efficacy of totally LTG(TLTG)and LATG in the context of radical gastrectomy for ***,we investigated the safety and feasibility of the total laparoscopic esophagojejunostomy *** Literature on comparative studies of the above two surgical methods for GC(TLTG group and LATG group)published before September 2022 were searched in the PubMed,Web of Science,Wanfang Database,CNKI,and other Chinese and English *** addition,the following search keywords were used:Gastric cancer,total gastrectomy,total laparoscopy,laparoscopy-assisted,esophagojejunal anastomosis,gastric/stomach cancer,total gastrectomy,totally/completely laparoscopic,laparoscopic assisted/laparoscopy assisted/laparoscopically assisted,and esophagojejunostomy/esophagojejunal *** Manager 5.3 software was used for the meta-analysis after two researchers independently screened the literature,extracted the data,and evaluated the risk of bias in the included *** After layer-by-layer screening,258 pieces of literature were recovered,and 11 of those pieces were eventually *** resulted in a sample size of 2421 instances,with 1115 cases falling into the TLTG group and 1306 cases into the LATG *** or sex differences between the two groups were not statistically significant,according to the meta-analysis,however the average body mass index of the TLTG group was considerably higher than that of the LATG group(P=0.01).Compared with those in the LATG group,the incision length in the TLTG

关键词： Total laparoscopic gastrectomy Laparoscopically assisted total gastrectomy Gastric cancer Meta-analysis

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