Background & Aims: The influence of sex hormones on chronic liver disease (CLD) progression remains unclear, despite sex-related differences in disease susceptibility and outcomes. This study aimed to investigate the associations of total testosterone (TT) and sex hormone-binding globulin (SHBG) levels with CLD-related outcomes across sex and menopausal status. Methods: A retrospective cohort study was conducted using UK Biobank data. Serum TT and SHBG levels were measured at baseline. Participants were followed for incident liver fibrosis and cirrhosis, hepatocellular carcinoma (HCC), and liver-related death. Cumulative risk curve, restricted cubic spline, and multivariable Cox proportional hazards models were used to assess TT and SHBG associations with outcomes in males, premenopausal females, and postmenopausal females. Results: A total of 155,997 males, 79,637 postmenopausal females, and 28,174 premenopausal females were included, with a median follow-up of 13.53 years. Cumulative risk curve showed that males had the highest risk of CLD-related outcomes ( P < 0.001). Males in the highest quartile of SHBG had hazard ratios (HRs) of 3.58 for liver fibrosis and cirrhosis, 4.31 for HCC, and 5.18 for liver-related death compared to the lowest quartile. In the highest TT quartile, the HRs were 2.17 for liver fibrosis and cirrhosis, 2.22 for HCC, and 2.50 for liver-related death. In postmenopausal females, only SHBG levels were positively associated with outcomes, though weaker than males. No significant associations were observed in premenopausal females. Conclusions: Elevated TT and SHBG levels are associated with higher risks of CLD-related outcomes, particularly in males. Further studies are needed to clarify the causal roles and mechanisms.

The D−− phenotype is an extremely rare Rh blood group variant with absence of C, c, E, and e antigens but preserved D expression, predisposing to anti-Rh17 alloimmunization and hemolytic disease of fetus and newborn (HDFN). We report a 25-year-old Chinese woman (gravida 3, para 1) with D+C−c−E−e− phenotype and a history of severe neonatal jaundice and fetal demise. In her current pregnancy, admitted at 25 ⁺⁵ weeks for elevated fetal middle cerebral artery peak systolic velocity. PacBio sequencing (proband and her parents) and Oxford Nanopore whole-genome sequencing (ONT WGS; proband) were performed. PacBio sequencing preliminarily identified a compound heterozygous state at the RHCE locus involving two distinct RHCE -null haplotypes, a paternal complex structural variant and a maternal RHCE*02N.03 null allele with seven mutations. Subsequent ONT WGS resolved a novel paternal chimeric RHD–TMEM50A–RHCE rearrangement arising from dual recombination events. Serological and family evidence suggest that the maternal RHCE*02N.03 allele with c.486 + 1G>A results in a C−e− null phenotype in the compound heterozygous state. Four serial intrauterine transfusions used allogeneic D−− donor blood or maternal autologous washed irradiated packed red blood cells. All transfusions were well tolerated, with delivery at 37 weeks by cesarean section and favorable neonatal outcomes. This case demonstrates a sequential transfusion strategy for D−− pregnancies—prioritizing allogeneic D−− blood from rare donor networks when available, with maternal autologous blood as a safe alternative—and, through complementary PacBio and ONT WGS, adds evidence that complex RHD-RHCE inversion-recombination events may represent recurret mechanisms in the Chinese population while refining RHCE*02N.03 annotation from C− to C−e−.

Atherosclerosis (AS) is a chronic cardiovascular disease. Traditional lipid-lowering treatments have not fully reduced the risk of disease onset in high-risk patients. This review provides a systematic overview of immune microenvironment remodeling and the mechanisms of pyroptosis during the onset and progression of atherosclerosis. Studies have shown that AS is not only related to abnormal lipid metabolism, but also closely associated with inflammatory responses, activation of immune cells, and programmed cell death. Immune cells, including macrophages, T cells, and B cells, play key roles in plaque formation, progression, and rupture. At the same time, NLR family pyrin domain containing 3 (NLRP3) inflammasome-mediated pyroptosis exacerbates plaque instability by promoting the release of inflammatory mediators, including Interleukin-1β (IL-1β) and interleukin-18 (IL-18), We further summarize emerging therapeutic strategies targeting immune regulation and pyroptosis pathways, including NLRP3 inhibitors, cytokine-targeted agents, and nano-drug delivery systems, thereby offering new perspectives for the precise treatment of AS.

Background: Mental health disorders among older adults in rural China present substantial public health challenges, yet their differential risk factors and practical screening tools remain understudied. Methods: We analyzed data from 4,180 participants in the Taierzhuang Aging Cohort. Using multivariate logistic regression, we identified independent risk factors for depression, anxiety, and insomnia. Predictor variables were confirmed to be sufficiently independent by evaluating bivariate correlations, variance inflation factors, and linearity in the logit. Corresponding nomograms were developed for risk prediction. Results: The prevalence of anxiety symptoms, depressive symptoms, and insomnia was 22.1%, 22.7%, and 29.5%, respectively. Multivariate analysis revealed distinct risk profiles for each condition: the absence of a chronic disease (OR: 1.57; 95% CI: 1.28–1.94) and older age were independent predictors of depressive symptoms; while a poor spousal relationship (OR: 1.55; 95% CI: 1.11–2.16) was a risk factor for anxiety symptoms, while physical activity 1–2 times/week (vs. ≥3 times/week: OR = 0.69; 95% CI: 0.53–0.90) was associated with decreased risk; inconstrast, female gender (OR: 1.33; 95% CI: 1.06–1.67) and lower exercise frequency were significantly associated with insomnia. Based on these findings, we developed three clinical prediction nomograms that integrate these independent predictors to facilitate individualized risk assessment. Conclusion: This study establishes distinct risk profiles for common mental health conditions in rural Chinese older adults and provides practical nomograms for risk assessment in primary care settings, facilitating targeted prevention strategies for these under-served populations.