The Relationship Between Systemic Lupus Erythematosus and Osteoporosis Based on Different Ethnic Groups: a Two-Sample Mendelian Randomization Analysis.

The previous observational studies could not overcome the effects of confounding variables and reverse causality. We aimed to determine whether there is a causal relationship between systemic lupus erythematosus and osteoporosis in East Asian and European populations, respectively, by two-sample Mendelian Randomization analysis. We obtained and downloaded data from publicly available genome-wide association study databases and analyses for East Asian and European populations, including systemic lupus erythematosus (SLE), osteoporosis (OP), multisite bone mineral density (BMD), and OP with fracture. After screening for instrumental single-nucleotide polymorphisms (SNPs) significantly correlated to SLE, the inverse-variance weighted (IVW) method was used for calculating the ratio and 95% confidence interval, besides utilizing MR-Egger, weighted median, and weighted mode to assess the robustness of the primary outcome. Moreover, multiple analyses, including MR-PRESSO, MR-Egger intercept, Cochran's Q test, as well as "leave-one-out" sensitivity, were used for evaluating horizontal pleiotropy, heterogeneity, and stability. Finally, we exchanged exposure and outcome and performed a reverse MR analysis. IVW (OR = 1.05, 95% CI = 1.01-1.09, P = 0.009) indicated a significant positive correlation between genetically predicted SLE and OP in East Asians. Furthermore, neither heterogeneity nor horizontal pleiotropy was observed. In Europe, there was no significant genetically predicted causal relation between SLE and OP. Bi-directional MR analysis showed no reverse causality between SLE and OP. In the East Asian population, genetically predicted SLE may have had a positive causal relationship with OP. In Europe, there is insufficient evidence for a potential causal relation between SLE and OP or BMD and fracture, and the correlations currently observed may be attributed to a variety of confounder variables.

[Current status of vaccination services for adults in urban and rural areas of nine provinces in China from 2019 to 2021].

Objective: To understand the current situation of vaccination services for adults in China, explore how to establish a stable and efficient vaccination service system for adults, and provide reference for formulating corresponding policies. Methods: The vaccination information systems of nine provinces in China were used to obtain information on urban and rural vaccination of influenza vaccine, 23-valent pneumococcal polysaccharide vaccine (PPV23), and human papillomavirus vaccine (HPV) from 2019 to 2021. The indicator, vaccination rate/full vaccination rate, was used for statistical description. Results: The vaccination rate/full vaccination rate of the three vaccines in eastern China was generally higher than that in central and western China. The vaccination rate/full vaccination rate in urban areas was generally higher than that in rural areas. From 2019 to 2021, the vaccination rates of influenza vaccine among people aged 60 years and above in urban and rural areas were 2.96%, 6.29%, 6.14% and 1.29%, 2.58%, 2.94%, respectively. The vaccination rates of the PPV23 among people aged 60 years and above in urban and rural areas increased year by year, with rates of 0.38%, 1.05%, 1.15% and 0.14%, 0.49%, 0.59%, respectively. From 2019 to 2021, the HPV coverage of female adults aged 27-45 years in urban and rural areas increased year by year, with rates of 0.46%, 0.93%, 1.88% and 0.17%, 0.40%, 1.08%, respectively. Conclusion: The vaccination rates of influenza vaccine,PPV23 vaccine and HPV vaccine for adults in China are relatively low, with higher rates in the eastern region than in the central and western regions, and higher rates in urban areas than in rural areas. It is recommended to formulate corresponding health and economic policies and explore a suitable vaccination service system for adults in China to improve vaccination rates.

[Association between obesity and risk for all-cause mortality in patients with type 2 diabetes].

Objective: To investigate the association between obesity and the risk for all-cause mortality in type 2 diabetes (T2DM) patients. Methods: The participants were from a rural community-based T2DM patient cohort in Zhejiang Province. The study used the data collected from baseline survey in 2016 and follow-up until December 31, 2021. A total of 10 310 participants were included, excluding those who were lost in follow-up or had incomplete data in follow-up. According to BMI and waist circumference, the study subjects were divided into 6 groups: low body weight, normal body weight, simple abdominal obesity, simple body obesity, complex overweight and complex obesity. Cox proportional hazards regression model was used to analyze hazard ratios (HRs) of all-cause mortality and their 95%CIs in T2DM patients with different obesity status. Results: The cumulative follow-up period was 57 049.47 person-years with an average follow-up of (5.53±0.89) person-years. During this period, 971 subjects died. The death density was 1 702.03/100 000 person-years. After adjusting for confounders, low-weight patients had a 104% increased risk for all-cause death compared with normal-weight patients (HR=2.04, 95%CI:1.42-2.92). The risk for all-cause death decreased by 34% (HR=0.66, 95%CI: 0.53-0.82), 22% (HR=0.78,95%CI: 0.66-0.92), 38% (HR=0.62, 95%CI: 0.49-0.78) in the patients with simple body obesity, complex overweight and complex obesity, respectively, there was no significant difference for all-cause death in the patients with simple abdominal obesity alone. In subgroup analysis, the risk of all-cause mortality increased in low-weight T2DM patients of different sexes and ages, the mortality risk in women with complex obesity was 50% lower than that in the women with normal body weight, but there was no significant difference in men in the comparison between complex obesity group and normal body weight group. The risk for all-cause mortality was significantly lower in ≥65 years old patients with simple body obesity, complex overweight and complex obesity than in patients with normal body weight (HR=0.61, 95%CI: 0.48-0.78; HR=0.76, 95%CI: 0.63-0.91; HR=0.56,95%CI: 0.42-0.73), there was no significant difference in the patients aged <65 years. There was no significant change in sensitivity analysis. Conclusions: There was an "obesity paradox" in the risk for all-cause mortality in T2DM patients. The risk of all-cause mortality in the low-weight patients was significantly higher than that in normal-weight patients, and the risk for death in the patients with simple body obesity or complex overweight and obesity were significantly lower.

[Overview of design and construction of hypertensive disorders of a pregnancy-cohort in Shenzhen].

Hypertensive disorder of pregnancy (HDP) involves two major public health issues: mother-infant safety and prevention and controlling major chronic disease. HDP poses a serious threat to maternal and neonatal safety, and it is one of the leading causes of maternal and perinatal morbidity and mortality worldwide, as well as an important risk factor for long-term cardiovascular disease (CVD). In order to explore effective strategies to prevent and control the source of CVD and reduce its risk, we have established a cohort of HDPs in Shenzhen for the primordial prevention of CVD. The construction of the HDP cohort has already achieved preliminary progress till now. A total of 2 239 HDP women have been recruited in the HDP cohort. We have established a cohort data management platform and Biobank. The follow-up and assessment of postpartum cardiovascular metabolic risk in this cohort has also been launched. Our efforts will help explore the pathophysiological mechanism of HDP, especially the pathogenesis and precision phenotyping, prediction, and prevention of pre-eclampsia, which, therefore, may reduce the risk of adverse pregnancy outcomes, and provide a bridge to linking HDP and maternal-neonatal cardiovascular, metabolic risk to promote the cardiovascular health of mothers and their infants.

Novel ALK-EML4 fusion with prominent mucous and hyaline stroma: Expanding the molecular genetic spectrum of S100 and CD34 positive spindle cell tumor

We report a case of a 49-year-old male patient suffering from an intraspinal tumor in the lumbar vertebra. The neoplasm was composed of mono-morphic spindle cells, arrayed in a patternless pattern in a background of prominent myxoid hyaline stroma with perivascular collagen rings in hyper-cellular regions. Instead, aggregated collagen fibers arranged into nodules and apparent calcium deposition were found in hypo-cellular regions. The tumor cells showed immunopositivity with S100 and CD34, whereas lacked SOX10 expression, which were reminiscent of a group of S100 and CD34 co-expression soft tissue spindle cell lesions having recurrent fusions including RAF1, BRAF, NTRK1/2/3, and RET genes. Interestingly, a novel anaplastic lymphoma kinase (ALK)- echinoderm microtubule-associated protein-like 4 (EML4) gene fusion was revealed. To our best knowledge, it was the first time to identify such gene fusion in the Orientals among this mentioned group, and it expands the molecular genetic spectrum of this specific group. The clinical relevance of this novel fusion requires further investigations.

Global microRNA profiles and signaling pathways in the development of cardiac hypertrophy

Hypertrophy is a major predictor of progressive heart disease and has an adverse prognosis. MicroRNAs (miRNAs) that accumulate during the course of cardiac hypertrophy may participate in the process. However, the nature of any interaction between a hypertrophy-specific signaling pathway and aberrant expression of miRNAs remains unclear. In this study, Spague Dawley male rats were treated with transverse aortic constriction (TAC) surgery to mimic pathological hypertrophy. Hearts were isolated from TAC and sham operated rats (n=5 for each group at 5, 10, 15, and 20 days after surgery) for miRNA microarray assay. The miRNAs dysexpressed during hypertrophy were further analyzed using a combination of bioinformatics algorithms in order to predict possible targets. Increased expression of the target genes identified in diverse signaling pathways was also analyzed. Two sets of miRNAs were identified, showing different expression patterns during hypertrophy. Bioinformatics analysis suggested the miRNAs may regulate multiple hypertrophy-specific signaling pathways by targeting the member genes and the interaction of miRNA and mRNA might form a network that leads to cardiac hypertrophy. In addition, the multifold changes in several miRNAs suggested that upregulation of rno-miR-331*, rno-miR-3596b, rno-miR-3557-5p and downregulation of rno-miR-10a, miR-221, miR-190, miR-451 could be seen as biomarkers of prognosis in clinical therapy of heart failure. This study described, for the first time, a potential mechanism of cardiac hypertrophy involving multiple signaling pathways that control up- and downregulation of miRNAs. It represents a first step in the systematic discovery of miRNA function in cardiovascular hypertrophy.