LDLR c.89_92dup: a novel frameshift variation in familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is a common inherited metabolic disease that causes premature atherosclerosis, cardiovascular disease, and even death at a young age. Approximately 95% of FH-causing genetic variants that have been identified are in the LDLR gene. However, only 10% of the FH population worldwide has been diagnosed and adequately treated, due to the existence of numerous unidentified variants, uncertainties in the pathogenicity scoring of many variants, and a substantial number of individuals lacking access to genetic testing. OBJECTIVE: The aim of this study was to identify a novel variant in the LDLR gene that causes FH in a Chinese family, thereby expanding the spectrum of FH-causing variants. METHODS: Patients were recruited from Beijing Anzhen Hospital, Capital Medical University. FH diagnosis was made according to the Dutch Lipid Clinical Network (DLCN) criteria. Whole-exome sequencing (WES) was conducted to identify the FH-causing variant in the proband, and amplicon sequencing was used to verify the variant in his family members. RESULTS: A three-generation Chinese family was recruited, and two FH patients were clinically diagnosed, both without known FH-causing variants. These two FH patients and another possible patient carried a novel variant, NC_000019.9(NM_000527.5):c.89_92dup (NP_000518.1:p.Phe32Argfs*21), in the ligand-binding domain of the low-density lipoprotein (LDL) receptor that led to a frameshift. The FH adults in the family showed severe clinical symptoms and statin therapy resistance. CONCLUSION: This study identified a novel pathogenic LDLR variant, c.89_92dup, associated with severe FH clinical manifestations and statin therapy resistance.

Sex Difference in Characteristics and Predictors of In-Hospital Mortality among Patients with COVID-19.

INTRODUCTION: With a surge in the prevalence of coronavirus disease-2019 (COVID-19) in Beijing starting in October 2022, hospitalisation rates increased markedly. This study aimed to evaluate factors associated with in-hospital mortality in patients with COVID-19. METHODS: Using data from hospitalised patients, sex-based differences in clinical characteristics, in-hospital management, and in-hospital mortality among patients diagnosed with COVID-19 were evaluated. Predictive factors associated with mortality in 1,091 patients admitted to the Beijing Anzhen Hospital (Beijing, China) for COVID-19 between October 2022 and January 2023 were also evaluated. RESULTS: Data from 1,091 patients hospitalised with COVID-19 were included in the analysis. In-hospital mortality rates for male and female patients were 14.9% and 10.4%, respectively. Multifactorial logistic analysis indicated that lymphocyte percentage (LYM%) (odds ratio [OR] 0.863, 95% confidence interval [CI] 0.805-0.925; p < 0.001), uric acid (OR 1.004, 95% CI: 1.002-1.006; p = 0.001), and high-sensitivity C-reactive protein (OR 1.094, 95% CI: 1.012-1.183; p = 0.024) levels were independently associated with COVID-19-related in-hospital mortality. Among female patients, multifactorial analysis revealed that LYM% (OR 0.856, 95% CI: 0.796-0.920; p < 0.001), older age (OR 1.061, 95% CI: 1.020-1.103; p = 0.003), obesity (OR 2.590, 95% CI: 1.131-5.931; p = 0.024), and a high high-sensitivity troponin I level (OR 2.602, 95% CI: 1.157-5.853; p = 0.021) were risk factors for in-hospital mortality. Receiver operating characteristic (ROC) curve analysis, including area under the ROC curve, showed that the efficacy of LYM% in predicting in-hospital death was 0.800 (sensitivity, 63.2%; specificity, 83.2%) in male patients and 0.815 (sensitivity, 87.5%; specificity, 64.4%) in female patients. CONCLUSION: LYM% is a consistent predictor of in-hospital mortality for both sexes. Older age and markers of systemic inflammation, myocardial injury, and metabolic dysregulation are also associated with a high mortality risk. These findings may help identify patients who require closer monitoring and tailored interventions to improve outcomes.

Mechanisms of and Potential Medications for Oxidative Stress in Ovarian Granulosa Cells: A Review.

Granulosa cells are essential for follicle initiation and development, and their abnormal function or apoptosis is a crucial factor leading to follicular atresia. A state of oxidative stress occurs when the balance between the production of reactive oxygen species and the regulation of the antioxidant system is disturbed. Oxidative stress is one of the most important causes of the abnormal function and apoptosis of granulosa cells. Oxidative stress in granulosa cells causes female reproductive system diseases, such as polycystic ovary syndrome and premature ovarian failure. In recent years, studies have confirmed that the mechanism of oxidative stress in granulosa cells is closely linked to the PI3K-AKT signaling pathway, MAPK signaling pathway, FOXO axis, Nrf2 pathway, NF-κB signaling pathway, and mitophagy. It has been found that drugs such as sulforaphane, Periplaneta americana peptide, and resveratrol can mitigate the functional damage caused by oxidative stress on granulosa cells. This paper reviews some of the mechanisms involved in oxidative stress in granulosa cells and describes the mechanisms underlying the pharmacological treatment of oxidative stress in granulosa cells.