No abstract

Left ventricular remodeling results in cardiac dysfunction and accounts for the majority of the morbidity and mortality following myocardial infarction (MI). The aim of the present study was to investigate the effect of asiatic acid (AA) on cardiac function and left ventricular remodeling in a rat model of MI and explore the underlying mechanisms. Rats were subjected to coronary artery ligation to model MI and orally treated with AA. After 4 weeks, cardiac function was assessed by echocardiography. Cardiomyocyte cross-sectional area was recorded, and the expression levels of a number of inflammatory cytokines were detected using ELISA. The degree of interstitial fibrosis was determined by evaluating the mRNA expression levels of collagen II and III. Western blot analysis was performed to detect the expression levels of total and phosphorylated p38 MAPK and ERK1/2, to investigate whether they are involved in the mechanism underlying the effect of AA on the heart. Rats subjected to MI displayed significantly impaired cardiac function compared with those subjected to a sham procedure, while this change was reversed by treatment with AA. Furthermore, AA markedly inhibited cardiac hypertrophy, reduced the mRNA expression levels of inflammatory cytokines and decreased interstitial fibrosis in the infarct border zone of MI model rats compared with those in vehicle-treated MI model rats. Furthermore, the phosphorylation of p38 MAPK and ERK1/2 was blocked by AA in the MI rats but not in the sham rats. In summary, AA treatment preserved cardiac function and inhibited left ventricular remodeling, potentially by blocking the phosphorylation of p38 MAPK and ERK1/2 in the infarct border zone of the ischemic myocardium, indicating that AA may be a novel candidate for development as a therapy for MI.

Changes in matrix metalloproteinase (MMP)-2, MMP-9, inflammation, blood coagulation factors and intestinal mucosal permeability in patients with active ulcerative colitis (UC) were investigated. A total of 50 active UC patients treated in our hospital from January 2016 to December 2018 were selected as the UC group, whereas 50 normal subjects receiving physical examination were selected as the control group. Venous blood was drawn to detect the content of early predictors, C-reactive protein (CRP), follistatin-like protein 1 (FSTL1) and D-dimer in serum. The disease activity index (DAI) score was recorded in both groups, the levels of MMP-2 and MMP-9 were determined, and the inflammatory factors interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF)-α were also detected. Moreover, the blood coagulation factors, platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen level were detected, the content of lactulose (L) and mannitol (M) in the urine after oral administration of L and M test liquid was determined via high-performance liquid chromatography in both groups, and the L/M ratio was calculated. In UC group, the content of CRP, FSTL1 and D-dimer was significantly higher than that in the control group (P<0.05). The DAI score was significantly higher (P<0.05), the content of MMP-2 and MMP-9 was remarkably raised (P<0.05), the platelet count, PT, APTT and fibrinogen level were all obviously increased (P<0.05), and the L/M ratio was notably lower (P<0.05) in the UC group than in the control group. In patients with active UC, MMP-2, MMP-9 and inflammatory factors were significantly increased, and there were changes in the blood coagulation factors and intestinal mucosal permeability, which further promote the occurrence and development of UC.

No abstract

The proportion of SubD was estimated to be 11.6% among T2DM patients in Beijing. Having more diabetic complications and being divorced/widowed made the odds of having SubD 8-fold and 3-fold higher than not having it, respectively. The relationship between SubD and diabetes necessitates early screening for milder forms of depression, which can alleviate the social burden and individual impairment from major depression or other chronic diseases.

Will individuals, especially high-risk individuals, avoid a disease test because of information avoidance? We conduct a field experiment to investigate this issue. We vary the price of a diabetes test (price experiment) and offer both a diabetes test and a cancer test (disease experiment) after eliciting participants’ subjective beliefs about their disease risk. We find evidence that, first, some people avoid the test even when there is neither a monetary nor a transaction cost, and second, both low- and high-risk individuals select out of the test as the price increases. We explain our findings using three classes of models of anticipatory utility. This paper was accepted by Yan Chen, decision analysis.

No abstract

Kidney disease is manifested in a wide variety of phenotypes, many of which have an important hereditary component. To delineate the genotypic and phenotypic spectrum of pediatric nephropathy, a multicenter registration system is being implemented based on the Chinese Children Genetic Kidney Disease Database (CCGKDD). In this study, all the patients with kidney and urological diseases were recruited from 2014 to 2020. Genetic analysis was conducted using exome sequencing for families with multiple affected individuals with nephropathy or clinical suspicion of a genetic kidney disease owing to early-onset or extrarenal features. The genetic diagnosis was confirmed in 883 of 2256 (39.1%) patients from 23 provinces in China. Phenotypic profiles showed that the primary diagnosis included steroid-resistant nephrotic syndrome (SRNS, 23.5%), glomerulonephritis (GN, 32.2%), congenital anomalies of the kidney and urinary tract (CAKUT, 21.2%), cystic renal disease (3.9%), renal calcinosis/stone (3.6%), tubulopathy (9.7%), and chronic kidney disease of unknown etiology (CKDu, 5.8%). The pathogenic variants of 105 monogenetic disorders were identified. Ten distinct genomic disorders were identified as pathogenic copy number variants (CNVs) in 11 patients. The diagnostic yield differed by subgroups, and was highest in those with cystic renal disease (66.3%), followed by tubulopathy (58.4%), GN (57.7%), CKDu (43.5%), SRNS (29.2%), renal calcinosis /stone (29.3%) and CAKUT (8.6%). Reverse phenotyping permitted correct identification in 40 cases with clinical reassessment and unexpected genetic conditions. We present the results of the largest cohort of children with kidney disease in China where diagnostic exome sequencing was performed. Our data demonstrate the utility of family-based exome sequencing, and indicate that the combined analysis of genotype and phenotype based on the national patient registry is pivotal to the genetic diagnosis of kidney disease.