Association between genetically proxied PCSK9 inhibition and systemic lupus erythematosus risk: A mendelian randomization study.

BACKGROUND: Preclinical and epidemiological studies suggest that proprotein convertase subtilisin/kexin type 9 (PCSK9) had a potential effect on the development of SLE, but it was unclear whether a causal relationship exists. We aimed to investigate the association between genetically proxied inhibition of PCSK9 and the risk of SLE using a two-sample Mendelian randomization (MR) approach. METHODS: Single nucleotide polymorphisms (SNPs) associated with PCSK9 were extracted from pooled data obtained from the Global Lipid Genetics Consortium (GLGC) Genome-wide Association Study (GWAS) related to LDL-c levels, which was used as a proxy for PCSK9 inhibition. Pooled statistics for SLE were obtained from an independent GWAS dataset including 5201 SLE patients and 9066 controls. Inverse variance-weighted random-effects models were used to examine the association between genetically proxied inhibition of PCSK9 and the risk of SLE. MR-Egger, weighted median, weighted mode, Simple mode, and co-location analyses were used as sensitivity analyses to test the robustness of the analyses. RESULTS: Genetically proxied inhibition of PCSK9 was associated with a reduced risk of SLE (OR = 0.51, 95% CI = 0.34 to 0.77, p = .001). This finding was replicated in an earlier GLGC GWAS analysis (OR = 0.59, 95% CI = 0.40 to 0.87, p = .007). Sensitivity analysis ensured that the results were robust. Co-localization analysis did not find evidence of shared causal variation between PCSK9 and SLE. CONCLUSIONS: This Mendelian randomization study showed that PCSK9 was associated with SLE pathogenesis, and its inhibition was associated with a reduced risk of SLE. This study has offered a prospective therapeutic avenue for intervening in the progression of SLE by inhibiting PCSK9 levels.

Long-term trends in Alzheimer's disease and other dementias deaths with high body mass index in China from 1990 to 2019, and projections up to 2042.

BACKGROUND: In China, the rising prevalence of high Body Mass Index (BMI) is linked to increasing health issues, including Alzheimer's disease (AD). This study analyzes mortality trends related to AD and other dementias associated with high BMI from 1990 to 2019, considering age, period, and birth cohort effects, and forecasts future trends. METHODS: We analyzed mortality data for AD and other dementias linked to high BMI in Chinese residents from the Global Burden of Disease 2019 database. Using Joinpoint regression, we examined age-standardized mortality rate (ASMR) trends and calculated annual and average annual percentage changes (APC and AAPC). Age-period-cohort models provided deeper insights, with Bayesian models used to project future ASMR trends to 2042. RESULTS: From 1990 to 2019, the ASMR for AD and other dementias associated with high BMI in China showed an overall increasing trend. Females had a lower increase rate than males, yet their overall levels remained higher. Specifically, the ASMR for males increased by an average of 2.70% per year, peaking between 2006 and 2010, while for females, it increased by an average of 2.29% per year, also peaking in the same period. Age-period-cohort analysis revealed increasing mortality relative risk with age and period, but a decrease with birth cohort. Projections suggest a continued rise in ASMR by 2042, with rates for males and females expected to be 2.48/100,000 and 2.94/100,000, respectively. CONCLUSION: The increasing mortality trend from AD and other dementias associated with high BMI highlights the urgent need for policy interventions focused on overweight prevention, particularly vital for addressing the health challenges in China's aging population.

Investigation on sleep-related cognition of Chinese health care workers during the first wave of COVID-19 pandemic.

Background: The COVID pandemic has brought tremendous negative effects on the mental health of health care workers, such as anxiety, depression, and sleep disorders. We conducted this study to evaluate the sleep-related cognition of Chinese health care workers (HCWs) during the first wave of COVID-19 pandemic and analyze its association with sleep quality, so as to provide scientific reference for improving sleep of HCWs. Patients and methods: A total of 404 HCWs from Yijishan Hospital of Wuhu City, China were enrolled in the study, selected by randomized cluster sampling in May 2020. We made a questionnaire to collect the general demographic information of the participants. The Pittsburgh Sleep Quality Index (PSQI) and a brief version of Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS-16) were used to measure sleep quality and sleep-related cognition, respectively. Results: The results showed that 312 HCWs (77.2%) had false beliefs and attitudes about sleep, while only 92 HCWs (22.8%) had correct beliefs about sleep. In addition, we found that those HCWs who were older, married, with a bachelor's degree or higher, nurses, more daily working hours (> 8 h) and monthly night shifts (≥ 5 times), had higher DBAS-16 scores (all p < 0.05). However, we did not find significant differences between men and women in DBAS-16 scores. According to the definition of PSQI, a total of 1/4 of the HCWs are poor sleepers and their DBAS-16 score was higher than good sleepers (t = 7.622, p < 0.001). In the end, we confirmed a positive correlation between sleep cognition and sleep quality (r = 0.392, p < 0.01). Conclusion: Our study revealed false beliefs and attitudes about sleep were prevalent among HCWs during the first wave of COVID-19 pandemic, and these false beliefs about sleep were closely correlated to sleep quality. We recommend fighting against these false beliefs about sleep.