1.A study on the association between insulin resistance and genome-wide DNA methylation based on Shanghai monozygotic twins
Jingyuan FENG ; Rongfei ZHOU ; Hongwei LIU ; Zihan HU ; Fei WU ; Huiting WANG ; Junhong YUE ; Zhenni ZHU ; Fan WU
Chinese Journal of Epidemiology 2024;45(7):932-940
Objective:To explore the association between insulin resistance (IR) and genome-wide DNA methylation based on Shanghai twin study.Methods:Monozygotic twins (MZ) from Shanghai were recruited during 2012-2013, 2017-2018, and 2022-2023. Data were collected by questionnaire survey, physical examination and laboratory tests. Genome-wide DNA methylation was quantified. Generalized linear mixed effect model was applied to analyze the association between methylation level at each site and homeostatic model assessment 2-insulin resistance (HOMA2-IR). Non-paired and paired designs were used to assess the association between DNA methylation and phenotype of IR. Cluster analysis was conducted to identify the clusters of top significant sites. Generalized linear regression was performed to examine the differential methylation patterns from clusters.Results:A total of 100 MZ pairs were included in this study. Hypermethylated cg10535199-2q23.1 ( β=0.74%, P=1.51×10 -7, OR=1.06, 95% CI: 1.03-1.09) and ch.17.49619327- SPOP ( β=0.23%, P=7.54×10 -7, OR=1.17, 95% CI: 1.08-1.28) were identified with suggestive significance. After correcting for multiple testing, no sites reached genome-wide significance. There was no statistical significance in the paired analysis. Two clusters with hypomethylated ( β=-0.39%, P<0.001) and hypermethylated ( β=0.47%, P<0.001) patterns were observed for HOMA2-IR. Conclusions:IR was significantly associated with DNA methylation, and genetic factors might contribute to the association.
2.Prognostic performance of pulmonary effective arterial elastance in patients with heart failure
Yihang WU ; Boping HUANG ; Jiayu FENG ; Liyan HUANG ; Xuemei ZHAO ; Jing WANG ; Jingyuan GUAN ; Xinqing LI ; Yuhui ZHANG ; Jian ZHANG
Chinese Journal of Cardiology 2024;52(4):397-404
Objective:To explore the predictive value of pulmonary effective arterial elastance (Ea) in patients with heart failure (HF).Methods:This is a retrospective cohort study, which retrospectively included 284 patients with HF who underwent right heart catheterization at Heart Failure Center in Fuwai Hospital between September 2013 and February 2022. Data regarding baseline clinical characteristics, hemodynamic profiles, and prognosis were collected. Ea was calculated as mean pulmonary arterial pressure/stroke volume. Patients were divided into Ea<0.555 group and Ea≥0.555 group according to the median value of Ea (0.555 mmHg/ml, 1 mmHg=0.133 kPa). The primary outcome was the primary clinical event, set as the first occurrence of a series of composite events, including all-cause death, heart transplantation, left ventricular assist device implantation, and HF rehospitalization. Event-free survival was defined as the absence of primary clinical events. Spearman correlation analysis was used to calculate the correlation coefficient between Ea and parameters reflective of right heart function. The Kaplan-Meier analysis was used to compare the different groups for the estimation of outcomes with the log-rank test. We used Cox proportional-hazards regression models to estimate hazard ratios ( HR) for primary clinical event. Subgroup analysis was performed based on the age, gender, New York Heart Association (NYHA) functional class, left ventricular ejection fraction, presence of pulmonary hypertension, and serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) values. We used receiver operating characteristic (ROC) curve to calculate the area under the curve ( AUC) of Ea for predicting event-free survival in patients with HF. Results:The median age was 51 years, and 206 (72.5%) patients were male. Ea and pulmonary vascular resistance (PVR) were significantly correlated ( r=0.698, P<0.001). The correlation between Ea and pulmonary arterial elastance (PAC) were even more significant ( r=-0.888, P<0.001). Compared with Ea<0.555 group, Ea≥0.555 group presented with higher serum NT-proBNP values (4 443 (1 792, 8 554) ng/L vs. 1 721 (480, 4 528)ng/L, P<0.001), higher PVR (3.4 (2.5, 4.7) Wood vs. 1.4 (0.9, 2.2) Wood, P<0.001), lower cardiac output (3.0 (2.3, 3.9) L/min vs. 4.3 (3.8, 4.9) L/min, P<0.001), and lower PAC (1.6 (1.3, 2.0) ml/mmHg vs. 4.0 (3.0, 6.0) ml/mmHg, P<0.001). The median follow-up time was 392 (166, 811) days. The Kaplan-Meier survival curve demonstrated a lower event-free survival rate in the Ea≥0.555 group compared to the Ea<0.555 group ( Plog-rank<0.001). After multivariate adjustment, Ea ( HR=1.734, P<0.001) remained significantly associated with the primary outcome. Subgroup analysis indicated that Ea was associated with the primary outcome across all subgroups. The AUC was 0.724 ( P<0.001) for Ea to predict event-free survival calculated from ROC analysis. Conclusions:Ea is closely related to parameters reflective of right ventricular afterload. Increased Ea is an independent predictor of adverse outcomes in patients with HF.
3.A biomechanical study of a self-designed axially controlled compression spinal rod for lumbar spondylolysis
Jingyuan LI ; Yulei WANG ; Nengqi SHAO ; Fanzhe FENG ; Jinlong LIANG ; Lijun WANG ; Wenxiang HUANG ; Yongqing XU ; Yi CUI
Chinese Journal of Orthopaedic Trauma 2024;26(7):611-617
Objective:To compare the mechanical properties between our self-designed axially controlled compression spinal rod (ACCSR) and conventional spinal rod (CSR) for lumbar spondylolysis (LS).Methods:This study selected 36 ACCSRs (the ACCSR group) and 36 CSRs (the CSR group), both of which were in a diameter of 6.0 mm and manufactured in the same batch. They were subjected respectively to biomechanical tests of spinal rod and pedicle screw-rod internal fixation system. In spinal rod tests: the stiffness and yield load of the spinal rods were calculated using four-point bending tests ( n=7) and comparisons were made between the 2 groups; spinal rod fatigue tests ( n=8) recorded the successful compression loads after 2.5 million cycles of loading and compared them with the maximum force at the isthmus of a normal adult's unilateral lumbar spine (198.72 N). In tests of the pedicle screw-rod internal fixation system, the axial compression tests ( n=7) measured the axial gripping capacity, the axial torsion tests ( n=7) the torsional gripping capacity, and the lateral compression tests ( n=7) the stiffness and yield load of pedicle screws in the 2 groups respectively. Results:The stiffness [(1,543.37±61.41) N/mm] and yield load [1,338.57 (1,282.00, 1,353.80) N] of ACCSR group were significantly smaller than those of CSR group [(3,797.63±156.15) N/mm and 4,059.95 (3,813.80, 4,090.89) N] ( P<0.05). The spinal rod fatigue tests showed that the respective loads of CSR and ACCSR passing the 2.5 million fatigue tests were 640.00 N and 320.00 N, both larger than the maximum force at the unilateral lumbar isthmus of a normal adult (198.72 N). There were no significant differences between the ACCSR group and the CSR group in the axial gripping capacity and torsional gripping capacity, as well as in stiffness and yield load of screws between the 2 groups ( P>0.05). Conclusions:In fixation of LS, although the yield load, stiffness and fatigue resistance of ACCSR are inferior to those of CSR, the biomechanical properties of the two sets of pedicle screw-rod internal fixation system are comparable. The fatigue resistance of ACCSR can meet the stress requirements of the normal human isthmus.
4.Approaches in vascularization of tissue-engineered bone and their research progress
Yulei WANG ; Jingyuan LI ; Nengqi SHAO ; Wenhao XU ; Fanzhe FENG ; Zhijun CAI ; Zhongzheng YU ; Xiaoqing HE ; Yongqing XU ; Yi CUI
Chinese Journal of Orthopaedic Trauma 2024;26(10):915-920
Tissue engineering bone technology, grounded in seed cells, cytokines, and scaffold supports, provides an effective solution for addressing extensive bone defects, demonstrating significant potentials in the field of bone repair. However, this technology still faces numerous challenges. Focusing on vascularization in engineered bones, this article reviews various methods to enhance vascularization within tissue-engineered bones, including multicellular co-culture, application of angiogenic factors, advanced 3D printing, and aid of surgical interventions. This article also analyses the latest research developments and the limitations of the methods, and speculates future research directions for tissue engineered bone.
5.The effect of thrombin in preventing endoleaks and promoting sac regression after endovascular repair of abdominal aortic aneurysm
Shilu ZHAO ; Jingyuan LUAN ; Qichen FENG ; Jinman ZHUANG
Chinese Journal of General Surgery 2024;39(11):850-854
Objective:To investigate the effect of thrombin in preventing endoleaks and promoting sac regression after endovascular repair of abdominal aortic aneurysm.Methods:Retrospective study was performed on patients with abdominal aortic aneurysm (AAA) who were admitted to Peking University Third Hospital for endovascular repair (EVAR) from May 2018 to May 2023. Thrombin injection was performed during EVAR in patients with high risk of endoleaks, and the success rate of the operation, perioperative mortality (30 d), incidence of endoleak, thrombin-related allergic reactions and ectopic embolism were observed.Results:In 83 patients, the technical success rate was 100% (83/83). The average operation time was (89.9±17.1) min. The average hospitalization was (5.8±1.3) days. There were no thrombin-related allergic reactions and ectopic embolism in peri-operation. The median follow-up time was 36 months. Five patients lost follow-up. During the follow-up period, 3 patients died, of which 2 died of acute myocardial infarction at 16 and 24 months, respectively, and 1 died of lung cancer at 34 months. The remaining 75 patients survived, with an overall survival rate of 96.2% (75/78). Type Ⅱ internal leakage occurred in 3 of the 75 patients, with an incidence of 4.0%. The maximum diameter and volume of the sac did not increase significantly during follow-up, and conservative treatment was performed. The mean maximum sac diameter of 75 patients was (43.8±7.4) mm, which was significantly lower than that of (61.4±14.4) mm before EVAR ( P<0.001). The sac volume was also significantly decreased [(125.5±54.1) cm 3vs. (239.3±145.1) cm 3, P<0.01]. Conclusions:The use of thrombin in the prevention and treatment of endoleak during EVAR is safe and effective after mid-term follow-up. In the follow-up of EVAR, attention should be paid to the change of sac volume.
6.Progress of application of the twin method in diabetes factorial studies
Jingyuan FENG ; Zhenni ZHU ; Fan WU
Shanghai Journal of Preventive Medicine 2023;35(1):70-77
Diabetes is a complex disease caused by the combined effects of genetic and environmental factors, which seriously affects people’s health level and living quality. As a special research tool, the twin method can be used to estimate the relative effects of genes and environment on diabetes-related traits. Moreover, compared with regular study subjects, twins have natural controls. The extended methods combined with genetic statistics and molecular biology techniques also help to analyze risk factors of diabetes and clarify the true relationship between exposure and outcome. This paper reviewed the progress of the application of the twin method to diabetes factorial studies in the past ten years at home and abroad, and summarized the advantages and limitations of the classical twin model, co-twin control studies, and genome-wide and epigenetic epidemiological studies.
7.Detection of hepatitis A virus in strawberry by digital RT-PCR and fluorescence quantitative RT-PCR
Mengqi JIAO ; Feng SHI ; Wenjiao YIN ; Jingyuan CAO ; Shengli BI
Chinese Journal of Experimental and Clinical Virology 2023;37(4):443-448
Objective:To establish a digital droplet RT-PCR(dRT-PCR) method for Hepatitis A virus (HAV), and compare it with Real time RT-PCR(RT-qPCR) method, and select the best method for detecting hepatitis A virus in strawberry.Methods:Extract HAV vaccine RNA, optimize the reaction conditions of dRT-PCR and evaluate its specificity; Alkaline elution -PEG concentration method was used to extract nucleic acid from strawberry samples. At the same time, dRT-PCR and RT-qPCR method were used to detect the sensitivity and inhibition rate of HAV vaccine RNA in pure water and strawberry matrix, and the recovery rate of HAV in artificially contaminated strawberry was compared, which was applied to the detection of commercially available samples.Results:The optimal annealing temperature for dRT-PCR reaction was 60 ℃, and the optimal concentrations of primers and probes were 0.4 μmol/L、0.4 μmol/L and 0.2 μmol/L, with good specificity. There is no significant difference in sensitivity between the two method in detecting HAV vaccine RNA in pure water and strawberry matrix. The inhibition rate of dRT-PCR is low. The recovery rates of dRT-PCR and RT-qRCR in the detection of strawberry samples contaminated with HAV at higher concentrations were 12.90±0.006% and 30.12±0.02%, respectively. The recovery rates of lower concentrations of HAV contaminated strawberry samples were 18.27±0.07% and 10.85±0.03%, respectively, and the difference was statistically significant ( P<0.05). When strawberry samples on the market were tested, the result of both method were negative. Conclusions:The sensitivity of dRT-PCR method established in this study is not significantly different from that of RT-qPCR in detecting HAV RNA in different substrates, but dRT-PCR has good tolerance to PCR reaction inhibitors and high recovery rate when detecting low concentration HAV. Both detection method can be used for quantitative detection of hepatitis A virus in strawberry, and can be selected according to the actual situation.
8.Radiofrequency ablation versus laparoscopic hepatectomy for hepatocellular carcinoma: a Meta-analysis
Qingbo FENG ; Jie QIU ; Yuanlin LIU ; Jian ZHANG ; Jingyuan HUANG ; Haoming WANG ; Kunming WEN
Chinese Journal of Hepatobiliary Surgery 2022;28(3):221-227
Objective:To compare the effectiveness and safety of laparoscopic hepatectomy (LH) versus radiofrequency ablation (RFA) in treatment of hepatocellular carcinoma (HCC).Methods:The medical literatures on LH and RFA for HCC were searched in PubMed, Web of Science, Embase, VIP, Wanfang, CNKI and other electronic databases. The retrieval date was from database construction to June 7, 2021. According to the inclusion and exclusion criteria, studies were extracted by two authors, and Revman 5.3 software was used to conduct a meta-analysis to compare differences in operation time, blood loss, length of hospital stay, total complications, overall survival and disease-free survival outcomes between the LH group and the RFA group.Results:Of 3 690 patients who were included in 32 studies, there were 1 708 patients in the LH group and 1982 patients in the RFA group. Meta-analysis showed that compared with the LH group, the RFA group had significantly shorter surgical duration ( MD=-86.41, 95% CI: -116.21--56.60), less blood loss ( MD=-213.22, 95% CI: -273.43--153.00), shorter hospital stay ( MD=-3.23, 95% CI: -4.13--2.32), and lower incidence of complications ( OR=0.33, 95% CI: 0.26-0.43). However, local recurrence rate was significantly higher ( OR=1.83, 95% CI: 1.38-2.41). (All P<0.05). The 5-year survival rate of the LH group was significantly better than the RFA group ( OR=0.68, 95% CI: 0.51-0.90, P=0.008). Conclusion:LH provided better overall survival outcomes and lower local recurrence rates than RFA in HCC patients.
9.IgA nephropathy standard dataset and quality control
Jingyuan XIE ; Yan OUYANG ; Jing CHEN ; Feng DING ; Leyi GU ; Lifeng ZHU ; Donglei FENG ; Yanyan SONG ; Zhangsheng YU ; Hong REN ; Nan CHEN
Chinese Journal of Nephrology 2022;38(6):543-549
Objective:To establish a IgA nephropathy (IgAN) standard dataset for the structured and standardization of IgAN clinical information, which will be beneficial to the integration and utilization of clinical information among different medical institutions. Therefore, the IgAN Expert Collaboration Group composed the "IgA Nephropathy Standard Dataset".Methods:Referring to the domestic information standards, guidelines, data standard and consensus of related fields, based on electronic medical history, the patient identification number was used as the primary key of the system to collect information. By standardizing each data element in the data set, the standardization of the management system in data and information exchange, data collaboration and sharing was ensured, and a quality control system was developed.Results:This standard dataset included 607 data elements and 8 business domains, which were patient information, medical history information, physical examination, laboratory examination, assistant examination, renal pathology, drug treatment, and follow-up, respectively. Each module was composed of module name, data element name, English name, definition, range, reference standard, etc. At the same time, a corresponding quality control system was formulated to evaluate data quality from multiple dimensions such as completeness, standardization, accuracy, timeliness, and security for ensuring the high quality and security of the data.Conclusion:The IgAN standard dataset is established, which will contribute to the structuration and standardization of clinical information of IgAN patients.
10.Risk factors and prognostic value of heart-type fatty acid binding protein in patients with heart failure
Yuyi CHEN ; Pengchao TIAN ; Changhong ZOU ; Jiayu FENG ; Yan HUANG ; Qiong ZHOU ; Mei ZHAI ; Xiaofeng ZHUANG ; Yihang WU ; Boping HUANG ; Jingyuan GUAN ; Jing WANG ; Xinqing LI ; Xuemei ZHAO ; Tianyu XU ; Yuhui ZHANG ; Jian ZHANG
Chinese Journal of Laboratory Medicine 2022;45(9):968-976
Objective:To investigate the prognostic value and related factors of heart-type fatty acid binding protein (H-FABP) in patients with heart failure.Methods:A total of 877 consecutive patients who were admitted to heart failure care unit of Fuwai hospital and diagnosed as heart failure from July 2015 to July 2017 were enrolled in this study. Baseline serum H-FABP concentration was measured by fluorescence lateral flow immunoassay. According to serum H-FABP levels, patients were divided into three groups: low H-FABP group (H-FABP≤4.04 ng/ml, n=292), middle H-FABP group (H-FABP 4.04-7.02 ng/ml, n=292) and high H-FABP group (H-FABP≥7.02 ng/ml, n=293). The general clinical characteristics were collected and compared among the three groups. According to whether heart failure was caused by coronary artery disease or not, patients with heart failure were divided into ischemic heart failure and non-ischemic heart failure. Multivariate linear regression analysis was performed to explore the independent risk factors of H-FABP. The primary endpoint events were the composite of all-cause death or heart transplantation. Multivariate Cox regression analyses, receiver operating characteristic (ROC) curves, risk prediction tests with multivariate Cox regression model and Kaplan-Meier analyses were conducted to investigate the relationship between H-FABP and the prognosis of heart failure. Results:Multivariate linear regression analysis showed that age, coronary artery disease, alanine aminotransferase, uric acid and N-terminal pro-B type natriuretic peptide (NT-proBNP) were positively associated with H-FABP (β=0.012, 0.238, 0.001, 0.345 and 0.063 respectively,all P<0.05), while female, hemoglobin, albumin, sodium, and estimated glomerular filtration rate (eGFR) were negatively associated with H-FABP (β=-0.184, -0.006, -0.016, -0.034 and -0.006 respectively, all P<0.05). One hundred and nineteen patients (13.6%) lost to follow-up, and 246 patients (32.5%) suffered from all-cause death or heart transplantation during the median follow-up duration of 931 (412-1 185) days. Multivariate Cox regression analysis showed that baseline H-FABP (log 2H-FABP) level was the independent predictor of all-cause death or heart transplantation in patients with heart failure ( HR=1.39, P<0.001). ROC curves showed that baseline H-FABP was a predictor of all-cause death or heart transplantation in patients with heart failure within 3 months, 1 year and 2 years (areas under the curves were 0.69, 0.69 and 0.71 respectively), and the best cut-off values were 5.85 ng/ml, 6.54 ng/ml and 6.54 ng/ml respectively. Risk prediction test with multivariate Cox regression model showed that baseline H-FABP could provide additional prognostic value in predicting all-cause death or heart transplantation for patients with heart failure on top of basic model and baseline NT-proBNP ( P<0.001). Taking 6.54 ng/ml and trisected levels of H-FABP as cut-off values respectively, Kaplan-Meier analyses showed that the survival rates were significantly different among the two or three groups ( P<0.001). Subgroup analyses showed that baseline H-FABP (log 2H-FABP) level was an independent predictor of all-cause death or heart transplantation in patients with ischemic heart failure ( HR=1.74, P<0.001), as well as in patients with non-ischemic heart failure ( HR=1.28, P=0.027). Conclusions:Age, sex, coronary artery disease, hemoglobin, albumin, alanine aminotransferase, sodium, eGFR, uric acid and NT-proBNP are associated with H-FABP level. Baseline H-FABP level is an independent predictor of all-cause death or heart transplantation in patients with heart failure. On top of basic model and baseline NT-proBNP, baseline H-FABP could provide additional prognostic value in predicting adverse events for patients with heart failure.

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