ObjectiveTo explore the causal association between venous thromboembolism (VTE) and cardiovascular disease (CVD) risks using a two-sample bidirectional Mendelian randomization (MR) study. MethodsThe single-nucleotide polymorphism (SNP) data associated with VTE and CVD from genome-wide association studies were obtained as instrumental variables. Inverse variance weighted (IVW) was used as the main MR method and other methods were used as supplementary methods. Cochran's Q test, the intercept term of MR-Egger, and MR-PRESSO were used to assess pleiotropy and heterogeneity to ensure the robustness of the results. ResultsThe IVW method suggested a causal association between VTE and atrial fibrillation (OR=1.033, 95%CI 1.009 to 1.058, P=0.008), but no association was identified between VTE and coronary artery disease (OR=0.994, 95%CI 0.974 to 1.023, P = 0.551), heart failure (OR=1.021, 95%CI 0.992 to 1.050, P=0.159) and myocardial infarction (OR=1.012, 95%CI 0.971 to 1.055, P=0.568). The results of Cochran's Q test showed that there was no heterogeneity in the MR analyses of VTE and CVD. The MR-Egger intercept analysis and the MR-PRESSO global testing did not detect potential horizontal pleiotropy, and the results were robust. Reverse MR analysis was used to verify the presence of reverse causal associations. The reverse MR analysis demonstrated that reverse causal associations between VTE and CVD were not evidenced. ConclusionThe results of the MR study demonstrated a causal association between VTE and atrial fibrillation, but not with coronary artery disease, heart failure or myocardial infarction.
Hypertension is a strong risk factor for atherosclerotic cardiovascular disease (ASCVD), heart failure, and microvascular complications. Hypertension is common among patients with diabetes. Recently, the American Diabetes Association (ADA) published a new position statement which updated the assessment and treatment for hypertensive patients with diabetes. This interpretation is intended to help Chinese clinicians to understand the new ADA position statement.
Objective To investigate the potential causal associations between 731 immune cell traits and atherosclerosis by Mendelian randomization (MR) analysis. Methods Using single nucleotide polymorphisms (SNPs) as instrumental variables, genome-wide association study (GWAS) summary statistics (GCST90001391 to GCST90002121) for 731 immune cell traits were obtained from the GWAS Catalog database, and the atherosclerosis dataset (finn-b-I9_CORATHER) was retrieved from the IEU database for MR analysis. The inverse variance weighted method, MR-Egger regression, weighted median, simple mode, and weighted mode approaches were employed to estimate the causal effects between the 731 immune cell traits and atherosclerosis, using odds ratio (OR) with 95% confidence interval (CI) as the effect size. Cochran Q test was used to assess heterogeneity. Horizontal pleiotropy was evaluated using the MR-Egger intercept test and the MR-PRESSO method. Leave-one-out analysis was conducted to examine the sensitivity of the causal estimates to individual SNPs. Results MR analysis revealed potential causal associations between 24 immune cell traits and atherosclerosis (P<0.05). Among them, human leucocyte antigen (HLA)-DR on plasmacytoid dendritic cells (DC) [OR=1.035, 95%CI (1.016, 1.054), P<0.001] and hematopoietic stem cell absolute count (HSCAC) [OR=1.049, 95%CI (1.021, 1.077), P<0.001] showed significant positive causal associations with atherosclerosis (P≤0.001), whereas CD86 on CD62L+ myeloid DC [OR=0.953, 95%CI (0.926, 0.981), P=0.001] exhibited a significant negative causal association with atherosclerosis (P≤0.001). The results of Cochran Q test, MR-Egger regression, and MR-PRESSO indicated P-values>0.05, suggesting no evidence of heterogeneity or horizontal pleiotropy in the causal estimates for these three immune cell traits. Reverse MR analysis, using the 24 immune cell traits as outcome variables, showed no evidence of causal association (P>0.05), supporting a unidirectional causal relationship from immune cells to atherosclerosis. Conclusion HLA-DR on plasmacytoid DC and HSCAC may serve as risk factors for atherosclerosis, while CD86 on CD62L+ myeloid DC may play a protective role against atherosclerosis.
ObjectiveTo investigate the significance of expression and correlation of pyruvate kinase M2 (PKM2) and yes association protein (YAP) in hepatocellular carcinoma (HCC) tissue, and then explore the relationship between the 2 kinds of protein. MethodsA total of 120 patients' HCC tissues and adjacent tissues were collected retrospectively, who treated in our hospital from Apr. 2010 to Oct. 2013, the expressions of PKM2 and YAP protein in these HCC tissues and adjacent tissues were detected by SP immunohistochemical method, and then analyzed the relationship between the expressions of PKM2 and YAP ptotein with the clinicopathological features of HCC. Of the 120 patients, the expressions of YAP and PKM2 protein and its mRNA in 50 cases of HCC tissues and adjacent tissues were also examined by Western blot and real-time PCR methods respectively. Results① The immunohistochemical results showed that, the positive rate of PKM2 protein and YAP protein in HCC tissues were 67.50% (81/120) and 71.67% (86/120) respectively, which were both higher than those of adjacent tissues[PKM2 protein:20.83% (25/120); YAP protein:29.17% (35/120)], P < 0.050. ② The expression of PKM2 protein was significantly positively correlated with the expression of YAP protein in HCC tissues (r=0.519, P < 0.001). ③ In HCC tissues, the expression of PKM2 protein was significantly correlated with the diameter of tumor, TNM staging, differentiation of HCC, and lever of alpha fetal protein (P < 0.050), and the expression of YAP protein was significantly correlated with the differentiation of HCC and lever of alpha fetal protein (P < 0.050). ④ Western blot results showed that, the expression levels of PKM2 protein and YAP protein in HCC tissues were 1.25± 0.11 and 1.08±0.10 respectively, which were significantly higher than those of adjacent tissues (PKM2 protein:0.38±0.01, YAP protein:0.41±0.02), P < 0.050. ⑤ Real-time PCR assays results showed that, basing the expressions of PKM2 mRNA and YAP mRNA in adjacent tissues (both as 1), expressions of PKM2 mRNA and YAP mRNA in HCC tissues were 11.38±0.35 and 19.96±0.48 respectively, which were both higher than those of adjacent tissues (P < 0.050). ConclusionPKM2 and YAP protein were related to the initiation of HCC, and they were also closely correlated with the differentiation and prognosis of HCC.
ObjectiveTo evaluate the relation between protein expression of RAS-association domain family 1A (RASSF1A) gene and the occurrence and development of vulvar cancer. MethodsImmunohistochemistry was used to detect the expression of RASSF1A protein in 9 normal vulvar tissues, 12 vulvar intraepithelial neoplasm (VIN) tissues, as well as 35 vulvar cancer tissue samples which were taken from patients treated during January 2008 to December 2010. Then, we analyzed the correlation between the RASSF1A protein expression and the clinical pathological features of vulvar cancer. ResultsThe expression of RASSF1A protein in vulvar cancer samples was significantly different from that in samples of normal vulvar tissues and VIN tissues (P<0.05). Significant difference also existed in the expression of RASSF1A protein between normal vulvar tissues and VIN tissues (P<0.05). The expression of RASSF1A protein was not significantly correlated with age, grade, stage, lymph nodes involvement and sites (lateral/median) of vulvar cancer (P>0.05). ConclusionInactivation of RASSF1A gene involves in the occurrence of vulvar cancer but has no significant correlation with its development. There is no obvious correlation between cancer sites, onset ages and the expression of RASSF1A protein.
Morning glory syndrome (MGS) is a congenital optic disc anomaly. The characteristic ophthalmoscopic findings consist of a generally enlarged, funnel-shaped and excavated optic disc, surrounded by an elevated annulus of chorioretinal pigment disturbance, with a central glial tuft, multiple narrow branches of retina vessels radiating from the disc. There are peripheral non-perfusion retinal areas in most cases. The pathogenesis of MGS remains unclear. MGS might be associated with many ocular and systemic abnormalities, involving facial, central nervous, cerebrovascular and endocrine systems. Persistent hyperplastic primary vitreous and retinal detachments (RD) are the most common ocular complications of MGS. The mechanism RD in MGS is unclear. Vitrectomy with long-acting gas or silicone tamponade and photocoagulation around the breaks or the enlarged disc might be efficient for rhegmatogenous RD of MGS. Early diagnosis is crucial for recognition and treatment of the ocular and systemic complications, and maintenance of the visual function.
ObjectiveTo investigate the causal relationship between gut microbiota and idiopathic pulmonary fibrosis (IPF). MethodsGenome-wide association studies (GWAS) data of gut microbiota and IPF were obtained from MiBioGen and Finngen databases, respectively. Instrumental variables were screened by means of significance, linkage disequilibrium, weak instrumental variable screening, and removal of confounding factors (genetics, smoking, host characteristics). Inverse variance weighted (IVW) was used as the main Mendelian randomization (MR) analysis method, and the weighted median, simple mode, MR-Egger, and weighted mode were used to perform MR to reveal the causal effect of gut microbiota and IPF. The Cochrane's Q, leave-one-out, MR-Egger-intercept, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and Steiger tests were used to analyze the heterogeneity, horizontal pleiotropy, outliers, and directionality, respectively. ResultsIVW analysis results showed that Actinomycetes [OR=1.773, 95%CI (1.323, 2.377), P<0.001], Erysipelatoclostridium [OR=2.077, 95%CI (1.107, 3.896), P=0.023], and Streptococcus [OR=1.35, 95%CI (1.100, 1.657), P=0.004] could increase the risk of IPF. Bifidobacterium [OR=0.668, 95%CI (0.620, 0.720), P<0.001], Ruminococcus [OR=0.434, 95%CI (0.222,0.848), P=0.015], and Tyzzerella [OR=0.479, 95%CI (0.304, 0.755), P=0.001] could reduce the risk of IPF. No significant heterogeneity, horizontal pleiotropy, outliers, and reverse causality were found. ConclusionActinobacteria, Erysipelatoclostridium and Streptococcus may increase the risk of IPF, while Bifidobacterium, Ruminococcus and Tyzzerella may reduce the risk of IPF. Regulation of the above gut microbiota may become a new direction in the study of the pathogenesis of IPF.
Objective To analyze whether there is a causal association between psoriasis and Alzheimer disease (AD) by a two-sample two-way Mendelian randomization (MR) method. Methods In the forward study, the single nucleotide polymorphisms (SNPs) associated with psoriasis were obtained from the comprehensive statistical data of the genome-wide association study database as the instrumental variables, and AD as the outcome; in the reverse study, the SNPs associated with AD were taken as instrumental variables, and psoriasis as the outcome. Using two-sample two-way MR analysis, the odds ratio (OR) value and 95% confidence interval (CI) of regression models, namely inverse variance weighted (IVW) method, MR-Egger regression method, weighted median method, simple pattern method, and weighted pattern method, were used to evaluate the causal relationship between psoriasis and AD. Cochran’s Q test was used to assess the heterogeneity of genetic instrumental variables, MR-Egger intercept method was used to test the horizontal pleiotropy of the assessment, “leave-one-out” method was used to assess the sensitivity of a SNP to the effect of causality, and the symmetry of funnel plot was observed to assess bias. Results A total of 19 SNPs associated with psoriasis were included as instrumental variables in the forward study. The IVW analysis of the forward study showed that there was a causal correlation between psoriasis and AD [OR=1.032, 95%CI (1.014, 1.051), P<0.001], and MR-Egger regression method [OR=1.042, 95%CI (1.012, 1.073), P=0.013], weighted median [OR=1.048, 95%CI (1.023, 1.074), P<0.001], and weighted model [OR=1.046, 95%CI (1.020, 1.073), P=0.002] all supported this result. Heterogeneity test (IVW result: Q=13.752, P=0.745; MR-Egger regression result: Q=13.134, P=0.727), MR-Egger intercept method (Egger intercept=–0.004, P=0.442), the results of “leave-one-out” method and funnel plot showed that the results of MR analysis were reliable. A total of 127 AD-related SNPs were included as instrumental variables in the reverse study. In reverse research, there was no evidence to support the AD could increase the risk of psoriasis (P>0.05). Heterogeneity test (IVW result: Q=232.496, P<0.001; MR-Egger regression result: Q=232.119, P<0.001) suggested heterogeneity, but MR-Egger intercept method (Egger intercept=0.003, P=0.652), the results of “leave-one-out” method and funnel plot showed that the results of MR analysis were reliable. Conclusion There is a causal association between psoriasis and AD, and psoriasis may increase the risk of AD.
ObjectiveA two-sample Mendelian randomization analysis was used to explore the causal associations between four basic body indices (basal metabolic rate, body fat percentage, BMI and hip circumference) and myasthenia gravis (MG). MethodsPooled gene-wide association study (GWAS) data were obtained from large publicly searchable databases, and four basic body indices were selected as the exposure factors and myasthenia gravis as the outcome factors, and single nucleotide polymorphisms (SNPs), which were strongly correlated with the phenotype of the exposure factors, were screened as the instrumental variables, and two-sample Mendelian randomization analyses were performed in order to assess the potential causal relationship between the exposure and the disease. ResultsInverse variance weighting (IVW) analysis showed that increased basal metabolic rate (OR=1.39, 95%CI 1.00 to 1.93, P=0.047), body fat percentage (OR=1.61, 95%CI 1.06 to 2.44, P=0.024), and hip circumference (OR=1.67, 95%CI 1.29 to 2.17, P<0.001) increased the risk of MG. But there was no significant causal relationship between BMI and MG. ConclusionBasal metabolic rate, body fat percentage and hip circumference have a positive causal relationship with MG, while BMI does not have a significant causal relationship with MG.
Under the background of a series of national policies, various forms of medical association have been established in recent years. The purpose of the medical association is to promote the coordination and integration of medical services and the rational distribution of medical resources. However, the implementation effect varies greatly. In the process of construction, there are problems such as the unsynchronized coordination and operation between the upper and lower levels, the inadequate integration of resources, the differences and conflicts in information standards and even cultural concepts, which limit the construction effect of the medical association to a certain extent. In order to solve these problems and explore a better path for the construction of medical association, this paper summarizes and analyzes the integrated development and construction measures of “discipline+operation” of the First People’s Hospital of Ziyang under the “government-hospital cooperation”, hoping to provide experience and reference for the construction of medical association to a certain extent through the summary and analysis, thus contributing to the better development of the construction of medical association.