Background::The association and its population heterogeneities between low-density lipoprotein cholesterol (LDL-C) and all-cause and cardiovascular mortality remain unknown. We aimed to examine the dose-dependent associations of LDL-C levels with specific types of cardiovascular disease (CVD) mortality and heterogeneities in the associations among different population subgroups.Methods::A total of 2,968,462 participants aged 35-75 years from China Health Evaluation And risk Reduction through nationwide Teamwork (ChinaHEART) (2014-2019) were included. Cox proportional hazard models and Fine-Gray subdistribution hazard models were used to estimate associations between LDL-C categories (<70.0, 70.0-99.9, 100.0-129.9 [reference group], 130.0-159.9, 160.0-189.9, and ≥190.0 mg/dL) and all-cause and cause-specific mortality.Results::During a median follow-up of 3.7 years, 57,391 and 23,241 deaths from all-cause and overall CVD were documented. We observed J-shaped associations between LDL-C and death from all-cause, overall CVD, coronary heart disease (CHD), and ischemic stroke, and an L-shaped association between LDL-C and hemorrhagic stroke (HS) mortality ( P for non-linearity <0.001). Compared with the reference group (100.0-129.9 mg/dL), very low LDL-C levels (<70.0 mg/dL) were significantly associated with increased risk of overall CVD (hazard ratio [HR]: 1.10, 95% confidence interval [CI]: 1.06-1.14) and HS mortality (HR: 1.37, 95% CI: 1.29-1.45). Very high LDL-C levels (≥190.0 mg/dL) were associated with increased risk of overall CVD (HR: 1.51, 95% CI: 1.40-1.62) and CHD mortality (HR: 2.08, 95% CI: 1.92-2.24). The stronger associations of very low LDL-C with risk of CVD mortality were observed in individuals with older age, low or normal body mass index, low or moderate 10-year atherosclerotic CVD risk, and those without diagnosed CVD or taking statins. Stronger associations between very high LDL-C levels and all-cause and CVD mortality were observed in younger people. Conclusions::People with very low LDL-C had a higher risk of all-cause, CVD, and HS mortality; those with very high LDL-C had a higher risk of all-cause, CVD, and CHD mortality. On the basis of our findings, comprehensive health assessment is needed to evaluate cardiovascular risk and implement appropriate lipid-lowering therapy for people with very low LDL-C.

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

BACKGROUND:The alteration of miR-146a-3p level is a common event in the pathogenesis of most neurological diseases,and the specific mechanism of miR-146a-3p regulation of astrocytes has not been studied. OBJECTIVE:To verify that miR-146a-3p regulates astrocyte proliferation,migration and apoptosis through insulin-like growth factor 1. METHODS:12 SD rats were divided into a sham operation group and a spinal cord injury group,with six rats in each group.RNA sequencing analysis was performed on the spinal cord tissues of all groups 2 weeks after surgery to screen out the differential genes(log2FC>2),and to select spinal cord injury-related genes(Score>20)in the Genecards database,and then to predict the target genes of miR-146a-3p by Targetscan.The intersection of three gene sets was obtained to screen out insulin-like growth factor 1 as one of the important target genes.qPCR,western blot assay and immunohistochemistry were performed to analyze the expression level of insulin-like growth factor 1 in spinal cord tissues.The primary astrocytes were divided into NC group,NC-mimics group and miR-146a-3p mimics group.Annexin-V/PI staining was used to detect cell apoptosis.CCK-8 assay was used to detect cell proliferation.Transwell assay was used to detect cell migration ability. RESULTS AND CONCLUSION:The expression of miR-146a-3p in the spinal cord tissue of the spinal cord injury group was lower than that of the sham operation group(P<0.05).The expression of insulin-like growth factor 1 in the spinal cord tissue of the spinal cord injury group was higher than that of the sham operation group(P<0.05).Compared with the NC group and NC-mimics group,the apoptotic rate of astrocytes was increased(P<0.01);the proliferation of astrocytes was decreased(P<0.01)and the number of migration was decreased(P<0.01)in the miR-146a-3p mimics group.To conclude,the expression of miR-146a-3p decreased and the expression of insulin-like growth factor 1 increased in spinal cord tissue after spinal cord injury.miR-146a-3p targeted regulation of insulin-like growth factor 1 in astrocytes,inhibited the proliferation and migration of astrocytes and promoted their apoptosis.

Fragile X syndrome(FXS)is caused by abnormal duplication and amplification of the FMR1 gene CGG.This article reports a pair of brothers diagnosed with FXS by genetic testing.Two patients,aged 15 and 14 years old respectively,both had clinical manifestations such as language disorders,intellectual disabilities,attention deficit disorder,autism spectrum disorder,and FXS's characteristic facial features.The proband had a rare late-onset epileptic seizure,which was well treated with levetiracetam,while his younger brother had no electroencephalogram abnormalities after repeated follow-up.This pair of cases suggests that the clinical phenotype of FXS has diversity and heterogeneity.

In the context of the high-quality development of public hospitals,it focuses on the task of improving the level of comprehensive budget management,with the difficulties and challenges in budget management in a certain hospital,it explores the path of building a smart financial system to serve comprehensive budget management.The practical application of the system has shown that information technology has effectively improved the budget management level of medical use.At a deeper level,case studies on the construction of the intelligent financial system demonstrate the importance of information technology in assisting hospitals with comprehensive budget management,elucidating the significance of information technology in improving the hospital budget management level and promoting high-quality development.

In the context of the high-quality development of public hospitals,it focuses on the task of improving the level of comprehensive budget management,with the difficulties and challenges in budget management in a certain hospital,it explores the path of building a smart financial system to serve comprehensive budget management.The practical application of the system has shown that information technology has effectively improved the budget management level of medical use.At a deeper level,case studies on the construction of the intelligent financial system demonstrate the importance of information technology in assisting hospitals with comprehensive budget management,elucidating the significance of information technology in improving the hospital budget management level and promoting high-quality development.

In the context of the high-quality development of public hospitals,it focuses on the task of improving the level of comprehensive budget management,with the difficulties and challenges in budget management in a certain hospital,it explores the path of building a smart financial system to serve comprehensive budget management.The practical application of the system has shown that information technology has effectively improved the budget management level of medical use.At a deeper level,case studies on the construction of the intelligent financial system demonstrate the importance of information technology in assisting hospitals with comprehensive budget management,elucidating the significance of information technology in improving the hospital budget management level and promoting high-quality development.

In the context of the high-quality development of public hospitals,it focuses on the task of improving the level of comprehensive budget management,with the difficulties and challenges in budget management in a certain hospital,it explores the path of building a smart financial system to serve comprehensive budget management.The practical application of the system has shown that information technology has effectively improved the budget management level of medical use.At a deeper level,case studies on the construction of the intelligent financial system demonstrate the importance of information technology in assisting hospitals with comprehensive budget management,elucidating the significance of information technology in improving the hospital budget management level and promoting high-quality development.

In the context of the high-quality development of public hospitals,it focuses on the task of improving the level of comprehensive budget management,with the difficulties and challenges in budget management in a certain hospital,it explores the path of building a smart financial system to serve comprehensive budget management.The practical application of the system has shown that information technology has effectively improved the budget management level of medical use.At a deeper level,case studies on the construction of the intelligent financial system demonstrate the importance of information technology in assisting hospitals with comprehensive budget management,elucidating the significance of information technology in improving the hospital budget management level and promoting high-quality development.

In the context of the high-quality development of public hospitals,it focuses on the task of improving the level of comprehensive budget management,with the difficulties and challenges in budget management in a certain hospital,it explores the path of building a smart financial system to serve comprehensive budget management.The practical application of the system has shown that information technology has effectively improved the budget management level of medical use.At a deeper level,case studies on the construction of the intelligent financial system demonstrate the importance of information technology in assisting hospitals with comprehensive budget management,elucidating the significance of information technology in improving the hospital budget management level and promoting high-quality development.