Objective:To investigate the level of endogenous hydrogen sulfide (H 2S) in contrast-induced acute kidney injury (CIAKI), as well as the potential role of H 2S against CIAKI by down-regulating NLRP3 inflammasome. Methods:Twenty-four healthy male Sprague-Dawley rats, weighing 180-220 g, were randomly divided into three groups according to the random number table method: control group, CIAKI group (iopromide 2.9 g/kg) and CIAKI+NaHS group (NaHS 4 mg/kg for three days before 2.9 g/kg iopromide injection). Kidneys were collected for whole-genome sequencing and bioinformatic analysis. HE and PAS staining were used for kidney histological examination. TUNEL assays were applied to detect renal tubular epithelial injury. Expressions of NLRP3 inflammasome (NLRP3, ASC and caspase-1) were evaluated by immunofluorescence staining. The role of H 2S in contrast (iopromide 200 mgI/kg)-induced injury on human renal tubular epithelium (HK-2 cells) was investigated, and CCK-8 assay was used to detect cellular viability. Results:Compared with the control group, the expression of endogenous H 2S synthetases-related genes [cystathionine β-synthase ( CBS), cystathionine-γ-lyase ( CSE) and 3-mercaptopyruvate sulfurtransferase ( 3- MST)] was lower in CIAKI group (all P<0.05). The gene expression levels of CBS, CSE and 3- MST were negatively correlated with renal function biomarkers serum creatinine, blood urea nitrogen and cystatin-C (all P<0.05). Compared with the CIAKI group, CIAKI+NaHS group showed alleviated creatinine, blood urea nitrogen and cystatin-C, improved histological changes, reduced apoptosis. Moreover, the expression levels of NLRP3, ASC and caspase-1 in CIAKI+NaHS group were lower than those in CIAKI group (all P<0.05). In HK-2 cells, compared with the contrast group, the cellular viability was higher in the contrast+NaHS group; reducing endogenous H 2S by CBS inhibitor could enhance contrast-induced cell viability ( P<0.05). Conclusions:Injury of endogenous H 2S system is pivotal to CIAKI pathogenesis. Up-regulation of H 2S ameliorates renal injury of CIAKI rats, which may be related to regulation of NLRP3 inflammasome.

Objective: To evaluate the prevalence and future trend of change of the disease burden of injuries in Chinese children and adolescents from 1990 to 2021, so as to provide reference for injury prevention and control in this population. Methods: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021), the trend of change in the disease burden of injuries in children and adolescents in China from 1990 to 2021 was analyzed by the Joinpoint regression model. The Bayesian age period cohort model (BAPC) was used to predict the disease burden of injuries among children and adolescents in China from 2022 to 2031. Results: From 1990 to 2021, the standardized incidence rate, standardized prevalence rate, standardized mortality rate, and standardized disability adjusted life years (DALYs) rate of injuries among children and adolescents in China showed an overall downward trend (AAPC=-1.14%, -0.76%, -5.41%, -5.03%, P <0.05). For different genders, the standardized incidence rate (7 106.00/100 000, 5 388.00/100 000), standardized mortality rate (92.00/100 000, 19.00/ 100 000 ), and standardized DALYs rate (7 834.00/100 000, 1 673.00/100 000) of injuries in boys were higher than the rate of injuries in girls in 1990 and 2021 (5 188.00/100 000, 3 874.00/100 000; 61.00/100 000, 10.00/100 000; 5 398.00/100 000, 945.00/100 000). Compared with Asia and globally, China had the fastest decline in the standardized mortality rate (AAPC= -5.41 ) and the slowest decline in the standardized prevalence rate (AAPC=-0.76) among children and adolescents. The results of the Joinpoint burden trend analysis demonstrated that the standardized incidence rate of injuries showed an increasing trend from 2005 to 2021, and the standardized prevalence rate of injuries showed an increasing trend from 2006 to 2021. Among the different age groups, the disease burden of injuries was highest in the 15-19-year-old group in 2021. For different types of injuries, the standardized incidence rate, standardized mortality rate, and standardized DALYs rate of unintentional injury were higher than those of transport injury, and self harm and interpersonal violence from 1990 to 2021. The BAPC prediction model showed that the standardized incidence rate ( 4 833.05/ 100 000-5 313.70/100 000) and standardized prevalence rate (5 433.90/100 000-5 821.88/100 000) of injury showed an increasing trend, and the standardized mortality rate (13.69/100 000-5.52/100 000) and the standardized DALYs rate ( 1 226.37/ 100 000-510.14/100 000) showed a decreasing trend during 2022-2031. The analysis of influencing factors found that children and adolescents who drank alcohol were at high risk of injury burden. Conclusions From 1990 to 2021, the injury burden of children and adolescents in China generally showed a downward trend. The standardized incidence rate and standardized prevalence rate of injuries are predicted to increase from 2022 to 2031. More targeted and individualized intervention measures should be developed to reduce the injury burden in children and adolescents.

BACKGROUND:Inherited heart disease has a high prevalence and mortality rate,but its pathogenesis has not yet been clarified.Although relevant animal models have been established to provide a foundation for the pathogenesis research of inherited heart disease,the value of these research results has been significantly reduced due to differences among species.Therefore,a new model is needed to explore its occurrence and development. OBJECTIVE:To review the current role of induced pluripotent stem cells in disease modeling and potential application prospects in various inherited heart diseases. METHODS:The first author searched the relevant articles published nearly 13 years in PubMed from January to March 2023.The search terms were"induced pluripotent stem cell,inherited heart disease,congenital heart disease".Finally,76 articles were included for analysis. RESULTS AND CONCLUSION:Since 2007,when induced pluripotent stem cells were induced from human somatic cells,many studies have been reported on disease-specific induced pluripotent stem cells.Due to the ability of disease-specific induced pluripotent stem cells to reproduce disease phenotypes,they are expected to become a new research tool for in vitro disease modeling,used to analyze pathogenesis and develop auxiliary drugs.In the research of cardiovascular genetic diseases,cardiomyocytes derived from patient-specific induced pluripotent stem cells contain gene mutations that are involved in cardiac dysplasia.Therefore,it can be used as a new tool to study the potential mechanisms of inherited heart disease.Up to now,induced pluripotent stem cells-derived cardiomyocytes have been widely used to study the molecular mechanisms of various genetic heart diseases,such as cardiac electrophysiological diseases,cardiomyopathy,and some syndromic inherited heart diseases.