Background: The interaction between intestinal microbiota and infertility is less researched. This study was performed to investigate the causal association between gut microbiota and infertility. Methods: In this two-sample Mendelian randomization (MR) study, genetic variants of intestinal microbiota were obtained from the MiBioGen consortium, which included 18,340 individuals. Inverse variance weighting (IVW), MR-Egger, weighted median, maximum likelihood, MR Robust adjusted profile score, MR Pleiotropy residual sum, and outlier (MR-PRESSO) methods were used to explore the causal links between intestinal microbiota and infertility. The MR-Egger intercept term and the global test from the MR-PRESSO estimator were used to assess the horizontal pleiotropy. The Cochran Q test was applied to evaluate the heterogeneity of instrumental variables (IVs). Results: As indicated by the IVW estimator, significantly protective effects of the Family XIII AD3011 group (OR = 0.87) and Ruminococcaceae NK4A214 group (OR = 0.85) were identified for female fertility, while Betaproteobacteria (OR = 1.18), Burkholderiales (OR = 1.18), Candidatus Soleaferrea (OR = 1.12), and Lentisphaerae (OR = 1.11) showed adverse effects on female fertility. Meanwhile, Bacteroidaceae (OR = 0.57), Bacteroides (OR = 0.57), and Ruminococcaceae NK4A214 group (OR = 0.61) revealed protective effects on male fertility, and a causal association between Anaerotruncus (OR = 1.81) and male infertility was detected. The effect sizes and directions remained consistent in the other five methods except for Candidatus Soleaferrea. No heterogeneity or pleiotropy were identified by Cochran’s Q test, MR-Egger, and global test (all p > 0.05). Conclusions: This two-sample MR study revealed that genetically proxied intestinal microbiota had potentially causal effects on infertility. In all, the Ruminococcaceae NK4A214 group displayed protective effects against both male and female infertility. Further investigations are needed to establish the biological mechanisms linking gut microbiota and infertility.

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This study aimed to describe the temporal trends and risk factors of kidney cancer (KC) burden from 1990 to 2021, evaluate its age, period, and cohort effects, and project the disease burden over the next 15 years. Data were derived from the 2021 Global Burden of Disease (GBD) study. A joinpoint regression model was used to estimate the average annual percentage change (AAPC) in KC prevalence and mortality, while age-period-cohort analysis was applied to estimate age, period, and cohort effects. We extended the Bayesian age-period-cohort (BAPC) model to predict the disease burden of KC from 2022 to 2036. In 2021, the number of incident KC cases in China reached 65,799 (4.62 cases per 100,000 total population). Additionally, KC resulted in 24,867 deaths (1.75 deaths per 100,000 total population).The incidence rate of KC continued to rise from 1.38 per 100,000 in 1990 to 4.62 per 100,000 in 2021, with males consistently exceeding females in case numbers. Meanwhile, KC mortality rose from 0.77 per 100,000 in 1990 to 1.75 per 100,000 in 2021.Throughout the study period, the average annual percent changes (AAPC) in incidence and mortality were 3.92% and 2.61%, respectively. Males exhibited higher prevalence and mortality of KC. In the Age-Period-Cohort (APC) analysis, the risk of KC was observed to increase with advancing age in the age dimension. Period effects analysis revealed an overall downward trajectory in all age groups. Cohort-level analysis indicated that early birth cohorts had higher susceptibility, with those born before 1920–1925 exhibiting a higher risk profile that subsequently decreased over time. Smoking and high body mass index (BMI) were the primary risk factors for KC-related disability-adjusted life years (DALYs) and mortality, while the contribution of occupational exposure to trichloroethylene was relatively minor. By 2036, the age-standardized incidence and mortality of KC are projected to rise to 4.58 and 1.31 per 100,000, respectively. To alleviate the disease burden of KC, comprehensive strategies are required, including risk factor prevention in primary care settings, KC screening for the elderly and high-risk populations, and access to high-quality medical services.

Most mammals tolerate exposure to hypobaric hypoxia poorly as it may affect multiple regulatory mechanisms and inhibit cell proliferation, promote apoptosis, limit tissue vascularization, and disrupt the acid–base equilibrium. Here, we quantified the functional state of germ cell development and demonstrated the interaction between the germ and somatic cells via single-cell RNA sequencing (scRNA-seq). The present study elucidated the regulatory effects of hypobaric hypoxia exposure on germ cell formation and sperm differentiation by applying enrichment analysis to genomic regions. Hypobaric hypoxia downregulates the genes controlling granule secretion and organic matter biosynthesis, upregulates tektin 1 (TEKT1) and kinesin family member 2C (KIF2C), and downregulates 60S ribosomal protein 11 (RPL11) and cilia- and flagella-associated protein 206 (CFAP206). Our research indicated that prosaposin-G protein-coupled receptor 37 (PSAP-GPR37) ligands mediate the damage to supporting cells caused by hypobaric hypoxic exposure. The present work revealed that hypoxia injures peritubular myoid (PTM) cells and spermatocytes in the S phase. It also showed that elongating spermatids promote maturation toward the G2 phase and increase their functional reserve for sperm–egg binding. The results of this study provide a theoretical basis for future investigations on prophylactic and therapeutic approaches toward protecting the reproductive system against the harmful effects of hypobaric hypoxic exposure.

To evaluate the efficacy and safety of high-activity placenta-derived mesenchymal stem cells (hPMSCs) in combination with low-intensity extracorporeal shock wave therapy (LI-ESWT) for the treatment of diabetic erectile dysfunction (ED). This prospective, randomized, controlled clinical trial enrolled 33 patients with refractory diabetic ED. Participants were randomly assigned in a 1:1:1 ratio to one of three groups: the hPMSCs group, the LI-ESWT group, or the combined therapy group (H + L). All subjects discontinued ED medications for at least two weeks prior to receiving the intervention. Treatment efficacy was assessed at baseline and at 1,3 and 6 months post-intervention using the International Index of Erectile Function – Erectile Function (IIEF-EF), Erection Hardness Score (EHS), Sexual Encounter Profile (SEP-2/SEP-3), and Rigiscan parameters, with safety outcomes monitored concurrently. At the 6-month follow-up, the combined therapy group demonstrated significantly superior outcomes compared to the individual hPMSCs and LI-ESWT groups. Specifically, total erection time reached 22.20 (15.20, 30.25) minutes (p = 0.001) and full erection time reached 11.90 (11.55, 12.35) minutes (p = 0.004) in the combined group. Moreover, EHS scores improved markedly, with 70% of patients in the combined group achieving an EHS > 2 at 6 months (p = 0.045). No severe adverse events were observed in any group; any local mild pain resolved within one week. The combination of high-activity hPMSCs and LI-ESWT appears to be a safe and effective strategy for improving erectile function in patients with diabetic ED, demonstrating a synergistic effect in prolonging erection duration and enhancing penile hardness. This combined therapeutic approach represents a promising new option for the clinical management of diabetic ED, warranting further validation in larger, multi-center studies to confirm its long-term efficacy and safety.