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Evaluating the influence of sarcopenia and myosteatosis on clinical outcomes in gastric cancer patients undergoing immune checkpoint inhibitor

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World Journal of Gastroenterology 2024年第8期30卷 863-880页

作者： Gui-Ming Deng Hai-Bin Song Zhong-Ze Du Ying-Wei Xue Hong-Jiang Song yuan-zhou Li Department of Gastrointestinal Surgery Harbin Medical University Cancer HospitalHarbin 150081Heilongjiang ProvinceChina Department of Radiology Harbin Medical University Cancer HospitalHarbin 150081Heilongjiang ProvinceChina

BACKGROUND The development and progression of gastric cancer(GC)are closely linked to the nutritional status of patients.Although immunotherapy has been demonstrated to be clinically effective,the relationships of sarcopenia and myosteatosis with the use of immune checkpoint inhibitors(ICIs)in patients with gastric cancer remain to be characterized.METHODS We performed a retrospective study of patients who were undergoing immuno-therapy for GC.For the evaluation of sarcopenia,the optimal cut-off value for the skeletal muscle index was established using receiver operating characteristic analysis of data obtained from pre-treatment computed tomography images at the L3 vertebral level.Myosteatosis was defined using the mean skeletal muscle density(SMD),with a threshold value of<41 Hounsfield units(HU)for patients with a body mass index(BMI)<25 kg/m^(2)and<33 HU for those with a BMI≥25 kg/m^(2).The log-rank test was used to compare progression-free survival(PFS)and overall survival(OS),and a Cox proportional hazard model was used to identify prognostic factors.Nomograms were developed to predict the PFS and OS of patients on the basis of the results of multivariate analyses.RESULTS We studied 115 patients who were undergoing ICI therapy for GC,of whom 27.4%had sarcopenia and 29.8%had myosteatosis.Patients with sarcopenia or myosteatosis had significantly shorter PFS and OS than those without these conditions.Furthermore,both sarcopenia and myosteatosis were found to be independent predictors of PFS and OS in patients with GC administering an ICI.The prediction models created for PFS and OS were associated with C-indexes of 0.758 and 0.781,respectively.CONCLUSION The presence of sarcopenia or myosteatosis is a reliable predictor of the clinical outcomes of patients with GC who are undergoing treatment with an ICI.

关键词： Gastric cancer Sarcopenia Myosteatosis,Immune checkpoint inhibitor Prognostic factor Overall survival Progression-free survival

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Integrative single-cell multiomics analyses dissect molecular signatures of intratumoral heterogeneities and differentiation states of human gastric cancer

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National Science Review 2023年第6期10卷 96-107页

作者： Shuhui Bian Yicheng Wang yuan zhou Wendong Wang Limei Guo Lu Wen Wei Fu Xin zhou Fuchou Tang Biomedical Pioneering Innovation Center School of Life Sciences Department of General Surgery Third Hospital Peking University State Key Laboratory of Reproductive Medicine and Offspring Health Nanjing Medical University Collaborative Innovation Center for Cancer Personalized Medicine Nanjing Medical University Beijing Advanced Innovation Center for Genomics (ICG) Ministry of Education Key Laboratory of Cell Proliferation and Differentiation Department of Pathology Peking University Third Hospital School of Basic Medical Science Peking University Health Science Center Peking University Third Hospital Cancer Center Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary Studies Peking University

Human gastric cancer is a highly lethal disease,but the underlying multiomic mole cular signatures remain largely uncle ar.Here,we performed multi-regional sampling,parallel single-cell multiomics sequencing and integrated analyses of human gastric cancer.We identified common transcrip tomic alterations of gastric cancer cells,such as aberrant down-regulation of genes associated with normal stomach function and up-regulation of KRT7,PI3,S100A4,etc.Surprisingly,aberrant and prevalent up-regulation of genes highly expressed in normal colorectal epithelial cells were also identified in cancer cells,which maybe partially regulated by promoter chromatin accessibility and DNA methylation levels.We reve aled the single-cell DNA methylome landscape of gastric cancer,and identified candidate DNA methylation biomarkers,such as hypermethylated promoters of TMEM240 and HAGLROS,and hypomethylated promoters of TRPM2-AS and HRH1.Additionally,the relationships between genetic lineages,D NA methylation and transcriptomic clusters were systematically revealed at single-cell level.We showed that DNA methylation heterogeneities were mainly among different genetic lineages of cancer cells.Moreover,we found that D NA methylation levels of cancer cells with poorer differentiation states tend to be higher than those of cancer cells with better differentiation states in the primary tumor within the same patient,although still lower than in normal gastric epithelial cells.Cancer cells with poorer differentiation states also prevalently down-regulated MUC1 expression and immune-related pathways,and had poor infiltration of CD 8+T cells.Our study dissected the mole cular signatures of intratumoral heterogeneities and differentiation states of human gastric cancer using integrative single-cell multiomics analyses.

关键词： gastric cancer single-cell multiomics analysis intratumoral heterogeneity tumor differentiation

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Ocular surface microbiota in patients with varying degrees of dry eye severity

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International Journal of Ophthalmology(English edition) 2023年第12期16卷 1986-1995页

作者： Xin-Rong Zou Pei Zhang yuan zhou Yao Yin Department of Ophthalmology Fengcheng HospitalFengxian DistrictShanghai 201411China Fengcheng Branch Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 201411China Department of Ophthalmology Huashan Hospital of Fudan UniversityShanghai 200040China Department of Ophthalmology Gonghui HospitalJing’an DistrictShanghai 200436China

AIM:To elucidate the profiles of commensal bacteria on the ocular surfaces of patients with varying severity of dry eye(DE).METHODS:The single-center,prospective,case-control,observational study categorized all participants into three distinct groups:1)control group(n=61),2)mild DE group(n=56),and 3)moderate-to-severe DE group(n=82).Schirmer’s tear secretion strips were used,and the bacterial microbiota was analyzed using 16S ribosomal ribonucleic acid gene sequencing.RESULTS:The three groups had significant differences in alpha diversity:the control group had the highest richness(Chao1,Faith’s phylogenetic diversity),the mild DE group showed the highest diversity(Shannon,Simpson),and the moderate-to-severe DE group had the lowest of the above-mentioned indices.DE severity was positively correlated with a reduction in beta diversity of the microbial community,with the moderate-to-severe DE group exhibiting the lowest beta diversity.Linear discriminant analysis effect size presented distinct dominant taxa that significantly differed between each.Furthermore,the exacerbation of DE corresponded with the enrichment of certain pathogenic bacteria,as determined by random forest analysis.CONCLUSION:As DE severity worsens,microbial community diversity tends to decrease.DE development corresponds with changes in microbial constituents,primarily characterized by reduced microbial diversity and a more homogenous species composition.

关键词： dry eye microbiota ocular surface tear film break up time

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MicroRNA–disease Network Analysis Repurposes Methotrexate for the Treatment of Abdominal Aortic Aneurysm in Mice

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Genomics, Proteomics & Bioinformatics 2023年第5期21卷 1030-1042页

作者： Yicong Shen yuanxu Gao Jiangcheng Shi zhou Huang Rongbo Dai Yi Fu yuan zhou Wei Kong Qinghua Cui Department of Physiology and Pathophysiology School of Basic Medical SciencesState Key Laboratory of Vascular Homeostasis and RemodelingPeking UniversityBeijing 100191China State Key Laboratory of Lunar and Planetary Sciences Macao University of Science and TechnologyMacao Special Administrative Region 999078China Department of Biomedical Informatics Center for Noncoding RNA MedicineSchool of Basic Medical SciencesPeking UniversityBeijing 100191China

Abdominal aortic aneurysm(AAA)is a permanent dilatation of the abdominal aorta and is highly lethal.The main purpose of the current study is to search for noninvasive medical therapies for AAA,for which there is currently no effective drug therapy.Network medicine represents a cuttingedge technology,as analysis and modeling of disease networks can provide critical clues regarding the etiology of specific diseases and therapeutics that may be effective.Here,we proposed a novel algorithm to quantify disease relations based on a large accumulated microRNA–disease association dataset and then built a disease network covering 15 disease classes and 304 diseases.Analysis revealed some patterns for these diseases.For instance,diseases tended to be clustered and coherent in the network.Surprisingly,we found that AAA showed the strongest similarity with rheumatoid arthritis and systemic lupus erythematosus,both of which are autoimmune diseases,suggesting that AAA could be one type of autoimmune diseases in etiology.Based on this observation,we further hypothesized that drugs for autoimmune diseases could be repurposed for the prevention and therapy of AAA.Finally,animal experiments confirmed that methotrexate,a drug for autoimmune diseases,was able to alleviate the formation and development of AAA.

关键词： Abdominal aortic aneurysm Network medicine MicroRNA-derived disease network Autoimmune disease Methotrexate

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The epidermal immune microenvironment plays a dominant role in psoriasis development,as revealed by mass cytometry

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Cellular & Molecular Immunology 2022年第12期19卷 1400-1413页

作者： yuan zhou Fan Xu Xue-Yan Chen Bing-Xi Yan Zhao-yuan Wang Si-Qi Chen Min Zheng Xiao-Yong Man Department of Dermatology Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina

Psoriasis is a common chronic inflammatory skin disease.The diversity and heterogeneity of immune cells in human skin have been studied in recent years,but the spatial distribution of immune cells at the single-cell level in the human psoriatic epidermis and dermis remains unclear.In this study,we mapped psoriatic skin immune cells from paired lesional,perilesional,and nonlesional skin samples using mass cytometry.Phenotypic dendritic cells(DCs)were found in the psoriatic epidermis and dermis.Psoriatic dermal CD1c^(+)CD11b^(+)cDC2s migrated to the epidermis in the perilesional skin during the preinitiation stage.CD1c^(+)CD11b^(+)cDC2s rapidly replaced EpCAM^(+)CD11c^(low) LC cells and initiated inflammation.Simultaneously,CD207^(+)CD11c^(hi) LC and CD5^(+)T cells accumulated in the psoriatic epidermis and orchestrated epidermal inflammation in psoriasis.The immune cell pool in the psoriatic dermis primarily included APCs and T cells.However,unlike that in the dermis,the epidermal immune environment was more significant and coincided with the inflammation occurring during psoriasis.

关键词： Psoriasis Cutaneous immune Mass cytometry Dendritic cell

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Roles of Cu doping in YbZn2Sb2 for thermoelectric performance enhancement

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Rare Metals 2024年第6期43卷 2869-2875页

作者： Xiong Zhang Hai-Hui Li Xiao-Liang Cao Bin Zhang Hong Wu Yu Zhang Guang Han Guo-Yu Wang Hao-Shuang Gu Xiao-yuan zhou College of Physics and Electronic Science Hubei Normal University Analytical and Testing Center Chongqing University School of Science Chongqing University of Posts and Telecommunications College of Materials Science and Engineering Chongqing University Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials-Hubei Key Laboratory of Ferro & Piezoelectric Materials and Devices Faculty of Physical and Electronic SciencesHubei University College of Physics Chongqing University

Recent research shows that increasing the carrier density after orbital alignment in AZn2Sb2（A=Ca,Yb,Eu,Sr,Mg） Zintl compounds yields remarkable results with regard to enhanced thermoelectric performance.However,research on carrier density increase via doping in these compounds is limited.In this study,we introduced Cu into the Zn sites in YbZn2Sb2and examined the thermoelectric properties.

关键词： Copper

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Acute mesenteric ischemia due to percutaneous coronary intervention:A case report

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World Journal of Clinical Cases 2022年第28期10卷 10244-10251页

作者： Peng Ding yuan zhou Kun-Lan Long Song Zhang Pei-Yang Gao Department of Critical Care Medicine Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072Sichuan ProvinceChina Department of Geriatrics The General Hospital of Western Theater CommandChengdu 610083Sichuan ProvinceChina

BACKGROUND Percutaneous coronary intervention(PCI) is extensively used to treat acute coronary syndromes(ACS).Acute mesenteric ischemia is a life-threatening disease if untreated.CASE SUMMARY An 81-year-old female presented with 3 d of lethargy and 1 d of dyspnea.On November 16,2021,the patient developed a coma.Her oxygen saturation dropped to 70%-80%,the patient was admitted to the intensive care unit for further treatment.Chest computed tomography(CT) showed chronic bronchitis,emphysema,and multiple lung infections.Abdominal CT scan showed no obvious abnormalities,but have severely calcified abdominal vessels.The patient received assisted ventilation,and vasoactive,and anti-infection drugs.Troponin level was elevated.Since the patient was in a coma,it could not be determined whether she had chest pain.The cardiologist assumed that the patient had developed ACS;therefore,the patient underwent PCI via the left femoral artery approach,and no obvious abnormalities were found in the left and right coronary arteries.On the second postoperative day,the patient presented with abdominal distension and decreased bowel sounds;constipation was considered and a glycerin enema was administered.On day 4,the patient suddenly lost consciousness,and had decreased blood pressure,abdominal wall swelling with increased tension,and absence of bowel sounds.An urgent abdominal CT scan revealed gas in her hepatic portal system with extensive bowel wall necrosis.The patient died on day 5 due to intractable shock.CONCLUSION The potential serious complications in patients undergoing PCI,especially the patients who are hemodynamically unstable and have severely calcified abdominal vessels,should all be considered.

关键词： Percutaneous coronary intervention Acute mesenteric ischemia Acute coronary syndrome Vascular calcification Case report

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Development of a novel virus-like particle-based vaccine for preventing tick-borne encephalitis virus infection

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Virologica Sinica 2023年第5期38卷 767-777页

作者： Jielin Tang Muqing Fu Chonghui Xu Bao Xue Anqi zhou Sijie Chen He Zhao yuan zhou Jizheng Chen Qi Yang Xinwen Chen Guangzhou National Laboratory Guangzhou510005China State Key Laboratory of Virology Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan430071China Guangzhou Institutes of Biomedicine and Health Chinese Academy of SciencesGuangzhou510530China GMU-GIBH Joint School of Life Sciences Guangzhou Medical UniversityGuangzhou511436China State Key Laboratory of Respiratory Disease Guangzhou Medical UniversityGuangzhou511436China

Tick-borne encephalitis virus(TBEV)is an important tick-borne pathogen that poses as a serious public health concern.The coverage and immunogenicity of the currently available vaccines against TBEV are relatively low;therefore,it is crucial to develop novel and effective vaccines against TBEV.The present study describes a novel strategy for the assembly of virus-like particles(VLPs)by co-expressing the structural(core/prM/E)and non-structural(NS2B/NS3Pro)proteins of TBEV.The efficacy of the VLPs was subsequently evaluated in C57BL/6 mice,and the resultant IgG serum could neutralize both Far-Eastern and European subtypes of TBEV.These findings indicated that the VLP-based vaccine elicited the production of cross-subtype reactive antibodies.The VLPs provided protection to mice lacking the type I interferon receptor(IFNAR^(-/-))against lethal TBEV challenge,with undetectable viral load in brain and intestinal tissues.Furthermore,the group that received the VLP vaccine did not exhibit significant pathological changes and the inflammatory factors were significantly suppressed compared to the control group.Immunization with the VLP vaccine induced the production of multiple-cytokine-producing antiviral CD4+T cells in vivo,including TNF-α^(+),IL-2^(+),and IFN-γ^(+)T cells.Altogether,the findings suggest that noninfectious VLPs can serve as a potentially safe and effective vaccine candidate against diverse subtypes of TBEV.

关键词： Tick-borne encephalitis virus(TBEV) Virus-like particle(VLP) Immunogenicity Neutralization Vaccine

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SENP3 Promotes Mantle Cell Lymphoma Development through Regulating Wnt10a Expression

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Current Medical Science 2024年第1期44卷 134-143页

作者： Yan-ni MA Yun-ding ZOU Zhi-long LIU Gui-xian WU yuan-ze zhou Cheng-xin LUO Xiang-tao HUANG Ming-ling XIE Shuang-nian XU Xi LI Department of Hematology Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Department of Hematology the Third Affiliated Hospital(Daping Hospital)Third Military Medical University(Army Medical University)Chongqing 400042China

Objective SUMO-specific protease 3(SENP3),a member of the SUMO-specific protease family,reverses the SUMOylation of SUMO-2/3 conjugates.Dysregulation of SENP3 has been proven to be involved in the development of various tumors.However,its role in mantle cell lymphoma(MCL),a highly aggressive lymphoma,remains unclear.This study was aimed to elucidate the effect of SENP3 in MCL.Methods The expression of SENP3 in MCL cells and tissue samples was detected by RT-qPCR,Western blotting or immunohistochemistry.MCL cells with stable SENP3 knockdown were constructed using short hairpin RNAs.Cell proliferation was assessed by CCK-8 assay,and cell apoptosis was determined by flow cytometry.mRNA sequencing(mRNA-seq)was used to investigate the underlying mechanism of SENP3 knockdown on MCL development.A xenograft nude mouse model was established to evaluate the effect of SENP3 on MCL growth in vivo.Results SENP3 was upregulated in MCL patient samples and cells.Knockdown of SENP3 in MCL cells inhibited cell proliferation and promoted cell apoptosis.Meanwhile,the canonical Wnt signaling pathway and the expression of Wnt10a were suppressed after SENP3 knockdown.Furthermore,the growth of MCL cells in vivo was significantly inhibited after SENP3 knockdown in a xenograft nude mouse model.Conclusion SENP3 participants in the development of MCL and may serve as a therapeutic target for MCL.

关键词： mantle cell lymphoma SENP3 cell proliferation apoptosis

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Potential threat of human pathogenic orthopoxviruses to public health and control strategies

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Journal of Biosafety and Biosecurity 2023年第1期5卷 1-7页

作者： Yongli Zhang yuan zhou Rongjuan Pei Xinwen Chen Yun Wang State Key Laboratory of Virology Center for Biosafety Mega-ScienceWuhan Institute of VirologyChinese Academy of Sciences.44 Hongshancelu AvenueWuhan 430071China Innovation Center for Pathogen Research Guangzhou LaboratoryGuangzhou 510320China

Orthopoxviruses(OPXVs)belong to a group of nucleo-cytoplasmic large DNA viruses.Human pathogenic OPXVs(hpOPXVs)include at least five viruses,among which smallpox virus and monkeypox virus are the most dangerous viral pathogens.Both viruses are classified as category-one human infectious pathogens in China.Although smallpox was globally eradicated in the 1980 s,it is still a top biosecurity threat owing to the possibility of either being leaked to the outside world from a laboratory or being weaponized by terrorists.Beginning in early May 2022,a sudden outbreak of monkeypox was concurrently reported in more than 100 disparate geographical areas,representing a public health emergency of international concern,as declared by the World Health Organization(WHO).In this review,we present the reasons for hpOPXVs such as monkeypox virus presenting a potential threat to public health.We then systematically review the historical and recent development of vaccines and drugs against smallpox and monkeypox.In the final section,we highlight the importance of viromics studies as an integral part of a forward defense strategy to eliminate the potential threat to public health from emerging or re-emerging hpOPXVs and their variants.

关键词： COVID-19 Control strategies Effect comparison

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