1.To explore the causal relationship between rheumatoid arthritis and iron deficiency anemia in European population by two-sample Mendelian randomization
Yong WANG ; Xiaoling YAO ; Yuzheng YANG ; Yi LING ; Xueming YAO ; Wukai MA
Acta Universitatis Medicinalis Anhui 2024;59(7):1251-1256
Objective To explore the causal relationship between rheumatoid arthritis(RA)and iron deficiency a-nemia(IDA)in European population by two-sample Mendelian randomization analysis.Methods The single nu-cleotide polymorphisms(SNPs)of RA and IDA were analyzed using public genome-wide association studies(GWAS).The inverse variance weighting method(IVW)was used as the main analysis method to evaluate the causal effect of RA on IDA.MR-Egger method,weighted median method(WM),weighted model method and simple model method were used as regression supplements to evaluate the robustness of sensitivity analysis results.The het-erogeneity function was used to calculate the P-value to test the heterogeneity,and the intercept term intercept was used to test the level pleiotropy.Results In the FINNGEN database at the genome-wide level,strong-related SNPs that removed linkage disequilibrium and met the P<5.0 × 10-8 by Mendelian randomization analysis were select-ed.After integrating exposure and outcome data,31 SNPs were obtained as the final effective instrumental variables.IVW showed that RA was a risk factor for IDA(the risk of IDA in RA patients was 1.064 times higher than that in non-RA patients,OR=1.064,95%CI:1.028-1.103).The weighted median method and MR-Egger method re-sults supported the positive correlation between RA and IDA.The intercept value was close to 0,indicating that there was no horizontal pleiotropy between exposure and outcome.The heterogeneity function's P<0.05 indicated that there was heterogeneity between exposure and outcome,but the random effect model test showed P<0.05,indi-cating that even if there was heterogeneity in causality,the overall trend was stable.Conclusion RA is a risk factor for IDA,and there is a positive correlation between RA and IDA.
2.Microbiomes combined with metabolomics reveals the changes of microbial and metabolic profile of articular cavity effusion in rheumatoid arthritis, urarthritis and osteoarthritis patients
Hanzhi Yi ; Wukai Ma ; Minhui Wang ; Chunxia Huang ; Guangzhao Gu ; Dan Zhu ; Hufan Li ; Can Liu ; Fang Tang ; Xueming Yao ; Liping Sun ; Nan Wang ; Changming Chen
Acta Universitatis Medicinalis Anhui 2024;59(12):2237-2245
Objective:
To investigate the changes of microorganisms and metabolites in joint effusion of patients with Rheumatoid arthritis(RA), Osteoarthritis(OA) and Urarthritis(UA). To provide new ideas for the study of the effect of microbiota on the pathogenesis of arthritis.
Methods:
Joint effusion samples were collected from 20 patients with RA, 20 patients with OA, and 20 patients with UA. 16S rRNA gene sequencing and untargeted ultra-high performance Liquid chromatography-mass spectrometry(LC-MS) were used to explore the differences in microorganisms and metabolites among the three groups. Pearson correlation analysis was used to detect the correlation between effusion microbiota and metabolites.
Results:
There were differences in microbial diversity and microbiota composition among the three groups. Combined with VIP>1 from OPLS-DA andP<0.05 from two-tailed Students t-test, 45 differential metabolites(Between RA and OA groups), 38 differential metabolites(Between UA and OA groups) and 16 differential metabolites(Between RA and UA groups), were identified. GO analysis and KEGG pathway analysis showed that the differential metabolic pathways among the three groups were mainly concentrated in citric acid cycle(TCA cycle), nucleotide metabolism, amino acid metabolism and glycolysis pathway. Correlation analysis of joint effusion microbiota and metabolites suggested that bacteria enriched in the three groups of joint effusion, such asPrevotella,Clostridium ruminosus,Prevotellaceae_UCG-001, were related to many key metabolites such as lysozyme, uric acid, glucose, and L-glutamine.
Conclusion
This study shows that there are a variety of bacterial flora in joint cavity effusion of RA, OA, and UA patients, and the differential metabolites produced by them are involved in the pathogenesis of the three types of arthritis by affecting a variety of metabolic pathways.
3.Development of a CLDN18.2-targeting immuno-PET probe for non-invasive imaging in gastrointestinal tumors
Yan CHEN ; Xingguo HOU ; Dapeng LI ; Jin DING ; Jiayue LIU ; Zilei WANG ; Fei TENG ; Hongjun LI ; Fan ZHANG ; Yi GU ; Steven YU ; Xueming QIAN ; Zhi YANG ; Hua ZHU
Journal of Pharmaceutical Analysis 2023;13(4):367-375
Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer.It has been identified as a promising target and a potential biomarker to diagnose tumor,evaluate efficacy,and determine patient prognosis.TST001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human Claudin18.2.In this study,we constructed a solid target radionuclide zirconium-89(89Zr)labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell lines.The[89Zr]Zr-des-ferrioxamine(DFO)-TST001 showed high radiochemical purity(RCP,>99%)and specific activity(24.15±1.34 GBq/μmol),and was stable in 5%human serum albumin,and phosphate buffer saline(>85%RCP at 96 h).The EC50 values of TST001 and DFO-TST001 were as high as 0.413±0.055 and 0.361±0.058 nM(P>0.05),respectively.The radiotracer had a significantly higher average standard uptake values in CLDN18.2-positive tumors than in CLDN18.2-negative tumors(1.11±0.02 vs.0.49±0.03,P=0.0016)2 days post injection(p.i.).BGC823CLDN18.2 mice models showed high tumor/muscle ratios 96 h p.i.with[89Zr]Zr-DFO-TST001 was much higher than those of the other imaging groups.Immunohistochemistry results showed that BGC823CLDN18.2 tumors were highly positive(+++)for CLDN18.2,while those in the BGC823 group did not express CLDN18.2(-).The results of ex vivo biodistribution studies showed that there was a higher distribution in the BGC823CLDN18.2 tumor bearing mice(2.05±0.16%ID/g)than BGC823 mice(0.69±0.02%ID/g)and blocking group(0.72±0.02%ID/g).A dosimetry estimation study showed that the effective dose of[89Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq,which is within the range of acceptable doses for nuclear medicine research.Taken together,these re-sults suggest that Good Manufacturing Practices produced by this immuno-positron emission tomog-raphy probe can detect CLDN18.2-overexpressing tumors.
4.Discussion on the regional medical scientific research alliance
Ran YI ; Tianyu CAO ; Yingxia XU ; Yingmei FENG ; Xueming CHEN ; Zhili JI
Chinese Journal of Medical Science Research Management 2019;32(3):176-178
Objective Through analyzing and summarizing the experiences and reflections during the construction of regional medical scientific research alliance,to explore the ultimate goal and ideal model of such work.Methods Literature review,as well as working experience summary and analysis.Results The purpose of setting up regional medical scientific research alliance lies in shared regional medical scientific research data information,using the two-way transformation model of laboratory and clinical research to support the medical service of primary health care in local hospitals,at the same time,promoting the construction and development of regional medical alliance.The ideal model is to make good use of the regional clini cal scientific research data sharing platform and related information sharing platform to promote the collaborative development of regional medical scientific research.Conclusions The ultimate goal of collaborative development of scientific research is to establish "an information map of regional scientific research resources",the map can be used for scientific research project cooperation,resource allocation,integration of scientific research forces and training of talent echelon,thereby comprehensively improve the regional research capacity.
5.Evaluation the effect of MALDI-TOF MS on the detection of carbapenemase produced by enterobacteriaceae
Xiaofang XIE ; Huiqin ZHOU ; Yi ZHENG ; Min WANG ; Xueming ZHU ; Hong DU
Chinese Journal of Laboratory Medicine 2019;42(2):135-139
Objective To evaluate the effect of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS)on the detection of carbapenemase producing enterobacteriaceae. Methods A total of 21 carbapenem non-susceptible enterobacteriaceaeclinical strains were collectedfrom the Second Affiliated Hospital of Soochow University during January to May, 2018, including 11 strains of Klebsiella pneumonia, 3 strains of Klebsiella oxytoca, 3 strains of Enterobacter cloacae, and 4 strains of Escherichia coli. All the isolates were incubated with 0.5g/L meropenem solution for 2 hours. The supernatant was centrifuged and collected for MALDI-TOF MS detection. The characteristic peaks were captured to determin whether the strain was producing carbapenemase or not. And then, the results were compared with PCR results by Kappastatistical analysis. Results The PCR results showed that all the strains were positive for carbapenmase genes, among them 15 isolates were encoding KPC genes, 6 isolates encoding GES genes, 2 isolates encoding NDM genes, 1 isolate encoding VIM genes, 4 isolates encoding GIM and 1 isolate encoding SIM. And the strains could carry one or more carbapem-resistant determinants. MALDI-TOF MS showed that meropenem were hydrolyzed by 21 isolates and a characteristic drug hydrolysis peak appeared at 199 m/z, as a result of carbapenemase produced by enterobacteriaceae. The assay of MALDI-TOF MS was highly consistentwith PCR results. Conclusions The investigation showed that MALDI-TOF MS can directly detect the carbapenemase by capture the characteristic drug hydrolysis peak.
6.Analysis of future scientific research work planning of the tertiary from the perspective of subject declaration
Ran YI ; Tianyu CAO ; Yingxia XU ; Yingmei FENG ; Xueming CHEN ; Zhili JI
Chinese Journal of Medical Science Research Management 2019;32(1):34-38
Objective From the perspective of the application of Beijing Tongzhou district science and technology project,we can grasp the present situation,existing problems and opportunities of the hospital.Methods Taking the information of the application declared by Beijing Luhe Hospital in 2017 as the research object,using the Excel,statistical analysis of the applicants'age,professional title,degree and departments distribution;summing up the common problems of the expert feedback.Results The study found that the 144 subjects participated in the declaration had been laying particular stress on each of the five areas,including:research category,applicants‘ age,professional title,degree and department.Conclusions Based on the data of the application,we have made a preliminary discussion about the overall planning and management measures of the future hospital scientific research.
7.Quality control and safeguarding measures for the whole-process management of scientific research in tertiary hospitals
Ran YI ; Tianyu CAO ; Yingxia XU ; Lejie GAO ; Xueming CHEN
Chinese Journal of Medical Science Research Management 2018;31(2):158-160,封3-封4
Objective Sharing and exploring the efficient development of scientific research management with peers in large tertiary general hospital.Methods This article took the whole process management of scientific research in our hospital during the past five years as example,analyzed and elaborated the quality control and related safeguarding measures.Results According to the comparison between 2012 and 2016,the number of SCI papers published,the number of National Natural Science Funding and other important indicators all have been increased significantly in our hospital.Conclusions The implementation of the whole process quality control management and security measures of scientific research helps hospital to achieve initial and efficient development in research management.
8.Investigation and analysis on the NSFC application capacity and existing problems of a tertiary general hospital in Beijing
Ran YI ; Tianyu CAO ; Yingxia XU ; Yingmei FENG ; Xueming CHEN ; Zhili JI
Chinese Journal of Medical Science Research Management 2018;31(6):433-436
Objective To achieve the hospital's scientific research objectives during the 13th five-year plan period,we designed to know about the potential NSFC application capacity and existed problems in our hospital.Methods Using "Questionnaire Star" network investigation platform to design questionnaire and conduct data analysis.Results Respondents are divided into two groups,one was who intend to apply in next three years while the other would not.it is found that there are obvious differences between the publication of SCI,as well as the previous research project application and conducting experiences.Conclusions In order to improve the rate of NSFC application,the hospital scientific management workers can consider doing the following:Improve the number of SCI papers published from the perspective of helping to encourage and forcing pressure.Strive for financial support from all parties and build a central experimental platform to create conditions for basic experiments for clinical medical workers.Regular and in time training for NSFC application.Some pressure when necessary to promote the extension of low-level study.Pay more attention to the incentives of research performance at the department level.
9.Operating efficiency of endoscopic centers in the United States and its inspirations
Wanying CHEN ; Yi SU ; Yuxiu LIU ; Xueming YI
Chinese Journal of Hospital Administration 2017;33(12):948-950
Growth of demand for endoscopic services and limited medical resources have brought the efficiency of endoscopic services in spotlight in the world .A retrospective efficiency analysis of endoscopic centers in the United States , as made by the authors , revealed their selection of efficiency indicators , benchmark establishment , evaluation and intervention .These efforts help summarize the experiences of improving efficiency and provide references for such centers in China to improve their efficiency .
10.Analysis of the hemolysin and virulence-related genes of incomplete hemolysis Staphylococcus aureus
Yi ZHENG ; Xiaofang XIE ; Hong DU ; Haifang ZHANG ; Xueming ZHU ; Min WANG ; Huan YANG ; Aiqing LI ; Ye JIANG ; Huiqin ZHOU
Chinese Journal of Clinical Infectious Diseases 2016;9(3):236-242
Objective To analyze hemolysin and virulence -related genes in incomplete hemolytic Staphylococcus aureus.Methods Fifty strains of incomplete hemolytic Staphylococcus aureus were isolated from patients admitted in the Second Affiliated Hospital of Soochow University during 2013 and 2014, and the isolates with complete hemolytic phenotype were also collected at the same period as the control strains . All the strains were inoculated and subcultured on four kinds of sheep blood agar plates supplied by different manufacturers to compare their hemolytic phenotype .The relative mRNA expressions of hemolysin genes (hla, hlb, hlc, hld) in standard strain, complete and incomplete hemolytic phenotype strains were detected by real-time quantitative polymerase chain reaction (RT-qPCR), and valued by 2 -△△Ct method.t test was used to compare mRNA expressions of hemolysin genes .Western blot was performed to analyze the expression of α-hemolysin.Antibiotic susceptibility test of incomplete hemolytic strains was performed using broth microdilution method.Resistant gene mecA and virulence genes pvl, tst were detected by PCR.Results The steady and hereditary incomplete hemolysis was observed in 50 strains of incomplete hemolytic Staphylococcus aureus on the sheep blood agar plates from different suppliers .Taking mRNA expression of hla, hlb, hlc, hld in standard strain as 1, the relative mRNA expressions of hemolysin genes in incomplete hemolytic strains were 0.02, 7.51, 0.06 and 0.12 respectively, there were statistical differences between standard strain and incomplete hemolytic strains (t =8.46, -56.40, 8.12 and 7.61, all P <0.05).And the expression of α-hemolysin was decreased in incomplete hemolytic strains .All the strains were identified as methicillin resistant Staphylococcus aureus (MRSA).Three strains exhibited different minimum inhibitory concentrations of teicoplanin and linezolid after subcultured , but the differences had no impact on the final results of antibiotic susceptibility test .mecA, pvl and tst genes were positive in incomplete hemolytic strains . Conclusion Staphylococcus aureus with incomplete hemolytic phenotype is methicillin resistant with higher expression of β-hemolysin and lower expressions of α-hemolysin, γ-hemolysin and δ-hemolysin.It carries plv and tst virulence genes and is of high virulence .


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