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Anatomic resection improved the long-term outcome of hepatocellular carcinoma patients with microvascular invasion:A prospective cohort study

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World Journal of Gastrointestinal Oncology 2021年第12期13卷 2190-2202页

作者： Jiang-Min Zhou Chen-Yang Zhou Xiao-Ping Chen Zhi-Wei Zhang Hepatic Surgery center Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030Hubei ProvinceChina Translational medicine center Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030Hubei ProvinceChina

BACKGROUND The long-term effect of anatomic resection(AR)is better than that of nonanatomic resection(NAR).At present,there is no study on microvascular invasion(MVI)and liver resection *** To explore whether AR improves long-term survival in patients with hepatocellular carcinoma(HCC)by removing the peritumoral *** A total of 217 patients diagnosed with HCC were enrolled in the *** surgical margin was routinely *** to the stratification of different tumor diameters,patients were divided into the following groups:≤2 cm group,2-5 cm group,and>5 cm *** In the 2-5 cm diameter group,the overall survival(OS)of MVI positive patients was significantly better than that of MVI negative patients(P=0.031).For the MVI positive patients,there was a statistically significant difference between AR and NAR(P=0.027).AR leads to a wider surgical margin than NAR(2.0±2.3 cm vs 0.7±0.5 cm,P5 cm,both AR and NAR fail to obtain wide surgical margin(0.6±1.0 cm vs 0.7±0.4 cm,P=0.491).CONCLUSION For patients with a tumor diameter of 2-5 cm,AR can achieve the removal of peritumoral MVI by obtaining a wide incision margin,reduce postoperative recurrence,and improve prognosis.

关键词： Microvascular invasion Hepatocellular carcinoma Anatomic resection Surgical margin Recurrence Surgery

Sinoatrial node pacemaker cells share dominant biological properties with glutamatergic neurons

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Protein & Cell 2021年第7期12卷 545-556页

作者： Dandan Liang Zhigang Xue Jinfeng Xue Duanyang Xie Ke Xiong Huixing Zhou Fulei Zhang Xuling Su Guanghua Wang Qicheng Zou Yi Liu Jian Yang Honghui Ma Luying Peng Chunyu Zeng Gang Li Li Wang Yi-Han Chen Department of Cardiology East HospitalTongji University School of MedicineShanghai 200120China Key Laboratory of Arrhythmias of the Ministry of Education of China Tongji University School of MedicineShanghai 200120China Institute of Medical Genetics Tongji UniversityShanghai 200092China Department of Regenerative medicine Tongji University School of MedicineShanghai 200092China Reproductive medicine center Tongji HospitalTongji University School of MedicineShanghai 200065China Department of Pathology and Pathophysiology Tongji University School of MedicineShanghai 200092China Department of Cardiology Daping HospitalChongqing 400042China Department of Neurology East HospitalTongji University School of MedicineShanghai 200120China State Key Laboratory of Cardiovascular Disease Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China

Activation of the heart normally begins in the sinoatrial node(SAN).Electrical impulses spontaneously released by SAN pacemaker cells(SANPCs)trigger the contraction of the ***,the cellular nature of SANPCs remains ***,we report that SANPCs exhibit glutamatergic neuron-like *** comparing the single-cell transcriptome of SANPCs with that of cells from primary visual cortex in mouse,we found that SANPCs co-clustered with cortical *** and cellular imaging confirmed that SANPCs contained key elements of glutamatergic neurotransmitter system,expressing genes encoding glutamate synthesis pathway(G/s),ionotropic and metabotropic glutamate receptors(Grina,Gria3,Grm1 and Grm5)t and glutamate transporters(Slc17a7).SANPCs highly expressed cell markers of glutamatergic neurons(Snap25 and S/-c17a7)t whereas Gad1,a marker of GABAergic neurons,was *** studies revealed that inhibition of glutamate receptors or transporters reduced spontaneous pacing frequency of isolated SAN tissues and spontaneous Ca2+transients frequency in single ***,our work suggests that SANPCs share dominant biological properties with glutamatergic neurons,and the glutamatergic neurotransmitter system may act as an intrinsic regulation module of heart rhythm,which provides a potential intervention target for pacemaker cell-associated arrhythmias.

关键词： sinoatrial node pacemaker cell glutamatergic neuron single-cell RNA-seq electrophysiology

Variants of genes encoding collagens and matrix metalloproteinase system increased the risk of aortic dissection

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Science China(Life Sciences) 2017年第1期60卷 57-65页

作者： Zongzhe Li Chengming Zhou Lun Tan Peng Chen Yanyan Cao Chenze Li Xianqing Li Jiangtao Yan Hesong Zeng Dao-Wu Wang Dao-Wen Wang Division of Cardiology Departments of Internal Medicine and Genetic Diagnosis CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and Technology Department of Cardiology the First Affiliated HospitalNanjing Medical University

Aortic dissection （AD） is a devastating, heterogeneous condition of aorta. The homeostasis between collagens and matrix metalloproteases （MMPs）/tissue inhibitors of MMPs （TIMPs） system in the extracellular matrix plays an important role for structure and functions of aorta. However, our knowledge on association between variants of genes in this system and pathogenesis of AD is very limited. We analyzed all yet known coding human genes of collagens （45 genes）, MMPs/TIMPs （27 genes） in 702 sporadic AD patients and in 163 matched healthy controls, by using massively targeted next-generation and Sanger sequencing. To define the pathogenesis of potential disease-causing candidate genes, we performed transcriptome sequencing and pedigree co-segregation analysis in some genes and generated Col5a2 knockout rats. We identified 257 pathogenic or likely pathogenic variants which involved 88.89% （64/72） genes in collagens-MMPs/TIMPs system and accounted for 31.05% （218/702） sporadic AD patients. In them, 84.86% patients （185/218） carried one variant, 12.84% two variants and 2.30% more than two variants. Importantly, we identified 52 novel probablY pathogenic loss-of-function （LOF） variants （20 nonsense, 16 frameshift, 14 splice sites, one stop-loss, one initiation codon） in 11.06% （50/452） AD patients, which were absent in 163 controls （P=2.5-10-5）. Transcriptome sequencing revealed that identified variants induced dyshomeostasis in expression of collagens-TIMPs/MMPs systems. The Col5a2-/- rats manifested growth retardation and aortic dysplasia. Our study provides a first comprehensive map of genetic alterations in collagens-MMPs/TIMPs system in sporadic AD patients and suggests that variants of these genes contribute largely to AD pathogenesis.

关键词： aortic dissection collagen matrix metalloproteinase next-generation sequencing genetic diagnosis

Propensity score-matched study and meta-analysis of cumulative outcomes of day 2/3 versus day 5/6 embryo transfers

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Frontiers of medicine 2017年第4期11卷 563-569页

作者： Ye Yin Ge Chen Kezhen Li Qiuyue Liao Sijia Zhang Nieying Ma Jing Chen Yan Zhang Jihui Ai Reproductive medicine center Tongii Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China Department of Obstetrics and Gynecology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China

The superiority of the cumulative outcomes of day 5/6 embryo transfer to those of day 2/3 embryo transfer in infertile couples has been debated. This retrospective study included data collected from 1051 patients from July 2011 to June 2014. Multiple maternal baseline covariates were subjected to propensity score matching analysis, and each day 5/6 group woman was matched to one day 2/3 group woman. A systematic meta-analysis was conducted to vaUdate the results. After matching was completed, 217 patients on the day 2/3 group were matched with those on the day 5/6 group, and no significant differences in the baseline characteristics were observed between the two groups. The cumulative pregnancy rate （57.14% vs. 53.46%, OR 1.16, 95% CI 0.79-1.70） and cumulative live birth rate （53.00% vs. 49.77%, OR 1.14, 95% CI 0.78-1.66） of day 5/6 embryo transfers were higher than those of day 2/3 embryo transfers, but this difference was not significant. The mean cycles per live birth and mean days per live birth in the day 5/6 group were significantly lower than those in the day 2/3 group. This study demonstrated that day 5/6 embryo transfer is a more cost-effective and time-efficient policy than day 2/3 embryo transfer to produce a live baby.

关键词： blastocyst embryo transfer cumulative pregnancy rate cumulative live birth rate IVF

Relationship between the Increase of Secretion of sTNF_α Induced by Lipopolysaccharides and the Enhanced Expression of TACE mRNA in HL-60 Cells and Adhesive Cells from Human Spleen

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Journal of tongji Medical University 2001年第4期21卷 265-268页

作者：丁廷波李凌波朱孔黎黄巍杨渝珍 Department of Molecular Biology Research Center of Experimental Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan 430030

In order to find out the potential modulators which influence the secretion of TNF α , the relationship between the amount of secreted TNF α (sTNF α ) and the level of TNF α converting enzyme (TACE) gene expression was studied before and after the stimulation by lipopolysaccharides (LPS) to HL 60 cells and adhered cells isolated from human spleen using cytological and molecular biology techniques and methods (RT PCR, Dot blot hybridization, etc.). The experimental results showed that: (1) LPS could induce the increase of expression of TNF α mRNA and TACE mRNA, reaching the peak value at 6 h and 10 h respectively after addition of LPS into cell culture medium; (2) The anti sense oligodeoxyribonucleotide (A ODN) complementary to TACE mRNA sequence really inhibited the secretion of TNF α as a result of blocked translation of TACE gene; (3) Furthermore, it was also observed that RDQ, a kind of injection derived from Chinese traditional herb, had strongly inhibitory effects on the expression of TACE mRNA and secretion of sTNF α stimulated by LPS. The above results suggested that the TACE indeed involved in delivering and processing of pro TNF α during the period of LPS stimulation and the study about the regulator/inhibitors of TACE gene expression would be very important to develop new types of therapy agents against toxic and side effects of sTNFα during the peroid of infection/inflammation to human body.

关键词： TNF α TNF α converting enzyme lipopolysaccharides anti sense oligodeoxyribonucleotide

ANALYSIS ON EPITOPES OF IGM WITH MONOCLONAL ANTI-ISOTYPIC AND ANTI-IDIOTYPIC ANTIBODIES AGAINST IgM FROM B-CLL

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Chinese Journal of Cancer Research 1992年第4期4卷 36-42页

作者：沈关心苏娜王晓林朱慧芬张悦秦立轩 Laboratory of Immunology Research Center of Experimental Medicine Tongji Medical University Wuhan Computer center Tongji Medical University Wuhan

A double antibodies additivity ELISA test was employed to identify the epltopes which can be recognized by monoclonal antibodies (McAbs) against IgM from B chronic lymphocyte leukemia (B-CLL). The computer grouping programme analysis showed that 4 and- isotypic MaAbs could be divided into two groups and 10 anti- idiotype McAbs could be divided into four groups. The result was consistent with that of the indirect sandwich ELISA and inhibition ELISA test. It suggested that there were at least 6 distinct IgM epitopes which can react specifically with 14 McAbs. Our study indicated that the combination of the additivity ELISA test and the computer grouping programme analysis is of help in studying the relationship of the structure and function of antigen.

关键词： antigen epltope, antibody, monoclonal additivity ELISA test, B chronic lymphocyte leukemia, computer grouping programme analysis.

Influence of Different Quality Sperm on Early Embryo Morphokinetic Parameters and Cleavage Patterns:A Retrospective Time-lapse Study

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Current Medical Science 2020年第5期40卷 960-967页

作者： Qiu-yue LIAO Bo HUANG Si-jia ZHANG Jing CHEN Ge CHEN Ke-zhen LI Ji-hui AI Reproductive medicine center Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Obstetrics and Gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

To investigate whether sperm with low concentration and motility can impact preimplantation embryos and to analyze how the effects present under a time-lapse incubation system,2905 oocytes were collected from 219 couples between January 2014 and December *** were divided into three groups according to sperm *** parameters and six cleavage patterns in the initial three cleavages were evaluated using the Primo Vision *** quality and clinic outcomes such as implantation rate,pregnancy rate and live birth rate were *** results showed that the concentration and motility of sperm correlated strongly with the rate of 2PN embryos,good-quality embryos on D3,blastocysts on D5/6 and good quality embryos on D5/*** time-lapse system recordings showed that compromised sperm quality could result in a significant delay in cc l and a decrease in cc2,and impact embryo developmental potential mainly through large fragments or/and blastomere fragmentation in the initial three *** conclusion,sperm with low concentration and motility can have paternal effects on preimplantation *** paternal effects present both as changes in morphokinetic parameters and cleavage patterns,which occur as early as fertilization and may cause severe damage to the preimplantation embryos.

关键词： embryo development patermal effect time-lapse morphokinetic parameters cleavage patterns

Human umbilical cord mesenchymal stem cells attenuate diabetic nephropathy through the IGF1R-CHK2-p53 signalling axis in male rats with type 2 diabetes mellitus

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第7期25卷 568-580页

作者： Hao ZHANG Xinshu WANG Bo HU Peicheng LI Yierfan ABUDUAINI Hongmei ZHAO Ayinaer JIEENSIHAN Xishuang CHEN Shiyu WANG Nuojin GUO Jian YUAN Yunhui LI Lei LI Yuntong YANG Zhongmin LIU Zhaosheng TANG Hua WANG Department of Endocrinology Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China Research center for Translational medicine Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China Department of Cardiology Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China Department of Biochemistry and Molecular Biology School of MedicineTongji UniversityShanghai 200331China Shanghai Institute of Stem Cell Research and Clinical Translation Shanghai East HospitalShanghai 200120China Ji’an hospital Shanghai East HospitalJi’an 343000China

diabetes mellitus(DM)is a disease syndrome characterized by chronic hyperglycaemia.A long-term high-glucose environment leads to reactive oxygen species(ROS)production and nuclear DNA *** umbilical cord mesenchymal stem cell(HUcMSC)infusion induces significant antidiabetic effects in type 2 diabetes mellitus(T2DM)***-like growth factor 1(IGF1)receptor(IGF1R)is important in promoting glucose metabolism in diabetes;however,the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains *** this study,a DM rat model was induced with high-fat diet feeding and streptozotocin(STZ)administration and rats were infused four times with *** glucose,interleukin-6(IL-6),IL-10,glomerular basement membrane,and renal function were *** that interacted with IGF1R were determined through coimmunoprecipitation *** expression of IGF1R,phosphorylated checkpoint kinase 2(p-CHK2),and phosphorylated protein 53(p-p53)was examined using immunohistochemistry(IHC)and western blot ***-linked immunosorbent assay(ELISA)was used to determine the serum levels of 8-hydroxydeoxyguanosine(8-OHdG).Flow cytometry experiments were used to detect the surface markers of *** identification of the morphology and phenotype of HUcMSC was performed by way of oil red“O”staining and Alizarin red *** rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane,increased the expression of IGF1 and ***1R interacted with CHK2,and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown *** cisplatin was used to induce DNA damage,the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin *** infusion ameliorated abnormalities and preserved kidney structure and function in DM *** expression of IGF1,IGF1R,p-CHK2,and p-p53,and the level of 8-OHdG in the DM group increased sign

关键词： Insulin-like growth factor 1 receptor(IGF1R) Checkpoint kinase 2(CHK2) Protein 53(p53) Diabetes mellitus Human umbilical cord mesenchymal stem cell(HUcMSC) DNA damage repair

Preliminary Evaluation of Safety of Conditionally Replication Adenovirus M4

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2012年第6期32卷 893-898页

作者：陈彩虹方海燕饶玉梅吴鹏何杨马丁高庆蕾 Cancer Biology Research center Tongji Hospital Tongji Medical College Huazhong University of Science and Technology center of Reproductive medicine the First Affiliated Hospital of Zhengzhou University Department of Obstetrics and Gynecology the First Affiliated Hospital of Zhengzhou University

Conditionally replication adenovirus M4, which was constructed in our lab, was proved to have good clinical application prospect for its good antitumor and antimetastasis effect. However, clinically applying M4 faces many problems. One of the most important is the safety of M4. In this study, we investigated the safety of M4 by comparing with Adv-TK, which was proved to be safe in Ⅰ–Ⅲ phase clinical trials. M4 and Adv-TK were injected into mice via the tail vein separately, and the mice were sacrificed at the indicated time. Blood was collected for biochemical tests, the liver was harvested for hematoxylin and eosin (H&E) staining and viral quantification, and splenic lymphocytes were separated for adenovirus specific cellular immune response. Our results showed that M4 had no obvious effect on mouse general symptoms. A transient reversible infiltration of inflammatory cells in collect abbacy was only observed in M4 group, and a transient slight increase in Cr level was detected both after M4 and Adv-TK injection. The adenovirus specific cellular immune response induced by M4 was similar to that by Adv-TK, and the distribution and metabolism of M4 in the mouse liver were also similar to those of Adv-TK. It was concluded that conditionally replication adenovirus M4 had the same safety as Adv-TK. The study provides safety basis for the coming clinical trials of M4.

关键词： conditionally replication adenovirus M4 safety blood biochemistry distribution