Examining the causal relationship between sex hormone-binding globulin (SHBG) and infertility: A Mendelian randomization study.

BACKGROUND: The causal relationship between sex hormone-binding globulin (SHBG) and infertility has remained unclear. Thus, we used Mendelian randomization (MR) to investigate this relationship. METHODS: Risk factors for SHBG were extracted from European individuals within the UK Biobank using single-nucleotide polymorphism (SNP) data. Summary-level data for infertility outcomes were obtained from the FinnGen dataset. The causal relationship between SHBG and infertility was examined using inverse variance weighted, weighted model, weighted median, and MR-Egger regression analyses. Additionally, Cochran's Q test and Egger intercept tests were used to confirm the heterogeneity and pleiotropy of identified instrumental variables (IVs). RESULTS: Our findings revealed a significant negative association between sex hormone-binding globulin (SHBG) levels and infertility, particularly with anovulation, a specific form of female infertility. However, SHBG did not exert a causal impact on male infertility or on female infertility of tubal origin. CONCLUSIONS: SHBG expression offers protection against the development of certain types of female infertility, suggesting it is a potential therapeutic target for infertility.

Direct Bilirubin, but not Indirect Bilirubin, is Associated with Short-term Adverse Events in HFpEF.

OBJECTIVE: Abnormal live function tests have been identified as independent risk factors for ominous prognosis in patients with heart failure. However, most of the previous studies have failed to determine the contribution of direct bilirubin (DBIL) and indirect bilirubin (IBIL) separately. Hence, we aimed to explore whether DBIL or IBIL is correlated with the prognosis of heart failure with preserved ejection fraction (HFpEF). METHODS: A total of 19837 patients were hospitalized for HFpEF between January 2012 and January 2022 in Fuqing City Hospital affiliated with Fujian Medical University. The primary endpoint was in-hospital all-cause mortality. Secondary endpoints included in-hospital cardiovascular mortality and 30-day re-admission for heart failure. RESULTS: Univariable analysis indicated that patients with elevated DBIL or IBIL were exposed to a higher risk of mortality and re-admission. However, in multivariable models, both ln-transformed DBIL and TBIL, but not IBIL, were independent risk factors for in-hospital all-cause mortality (hazard ratio (HR)=1.796, 95% confidential interval (CI)=1.477-2.183, P<0.001; HR=1.854, 95% CI=1.461-2.352, P.0.001; HR=1.161, 95% CI=0.959-1.407, P=0.126) and in-hospital cardiovascular mortality (HR=1.831, 95% CI=1.345-2.492, P.0.001; HR=1.899, 95% CI=1.300-2.773, P=0.001; HR=1.145, 95% CI=0.841-1.561, P=0.389). Only DBIL remained independently associated with 30-day readmission for heart failure (HR=1.361, 95% CI=1.036-1.787, P=0.027). Adding ln-transformed DBIL to model 1 increased its discriminatory capacity (C-statistic: 0.851 to 0.869, respectively), whereas adding ln-transformed IBIL yielded little increment (C-statistic: 0.851 to 0.852, respectively). CONCLUSION: DBIL, but not IBIL, was associated with short-term ominous prognosis in patients with HFpEF. Hence, DBIL may be the superior predictor for prognosis in HFpEF.

Elevated plasma pyruvate kinase M2 concentrations are associated with the clinical severity and prognosis of coronary artery disease.

Introduction: Pyruvate kinase M2 (PKM2) was involved in the pathophysiology of atherosclerosis and coronary artery disease (CAD). We tested whether plasma PKM2 concentrations were correlated with clinical severity and major adverse cardiovascular events (MACEs) in CAD patients. Materials and methods: A total of 2443 CAD patients and 238 controls were enrolled. The follow-up time was two years. Plasma PKM2 concentrations were detected by enzyme-linked immunosorbent assay (ELISA) kits (Cloud-Clone, Wuhan, China) using SpectraMax i3x Multi-Mode Microplate Reader (Molecular Devices, San Jose, USA). The predictors of acute coronary syndrome (ACS) were assessed by logistic regression analysis. The association between PKM2 concentration in different quartiles and MACEs was evaluated by Kaplan-Meier (KM) curves with log-rank test and Cox proportional hazard models. The predictive value of PKM2 and a cluster of conventional risk factors was determined by Receiver operating characteristic (ROC) curves. The net reclassification improvement (NRI) and the integrated discrimination improvement (IDI) were utilized to evaluate the enhancement in risk prediction when PKM2 was added to a predictive model containing a cluster of conventional risk factors. Results: In CAD patients, PKM2 concentration was the independent predictor of ACS (P < 0.001). Kaplan-Meier cumulative survival curves and Cox proportional hazards analyses revealed that patients with a higher PKM2 concentration had higher incidence of MACEs compared to those with a lower PKM2 concentration (P < 0.001). The addition of PKM2 to a cluster of conventional risk factors significantly increased its prognostic value of MACEs. Conclusion: Baseline plasma PKM2 concentrations predict the clinical severity and prognosis of CAD.