BACKGROUND: Pulmonary arterial hypertension (PAH) presents a significant health burden in Asia and remains a critical challenge. This study aims to delineate the PAH burden in Asia from 1990 to 2021. METHODS: Using the latest data from the Global Burden of Disease 2021, we evaluated and analyzed the distributions and patterns of PAH disease burden among various age groups, sexes, regions, and countries in Asia. Additionally, we examined the associations between PAH disease burden and key health system indicators, including the socio-demographic index (SDI) and the universal health coverage (UHC) index. RESULTS: In 2021, there were 25,989 new PAH cases, 103,382 existing cases, 13,909 PAH-associated deaths, and 385,755 DALYs attributed to PAH in Asia, which accounted for approximately 60% of global PAH cases. The age-standardized rates (ASRs) for prevalence and deaths were 2.05 (95% uncertainty interval [UI]: 1.66-2.52) per 100,000 population and 0.31 (95% UI: 0.23-0.38) per 100,000 population, respectively. From 1990 to 2021, Asia reported the lowest ASRs for PAH prevalence but the highest ASRs for deaths compared to other continents. While the ASRs for prevalence increased slightly, ASRs for mortality and DALYs decreased over time. This increasing burden of PAH was primarily driven by population growth and aging. The burden was especially pronounced among individuals aged ≥60 years and <9 years, who collectively accounted for the majority of deaths and DALYs. Moreover, higher SDI and UHC levels were linked to reduced incidence, but higher prevalence rates. CONCLUSIONS Although progress has been made in reducing PAH-related mortality and DALYs, the disease continues to impose a substantial burden in Asia, particularly among older adults and young children. Region-specific health policies should focus on improving early diagnosis, expanding access to treatment, and effectively addressing the growing PAH burden in the region.
Humans ; Global Burden of Disease ; Male ; Female ; Middle Aged ; Adult ; Asia/epidemiology* ; Prevalence ; Aged ; Pulmonary Arterial Hypertension/mortality* ; Adolescent ; Young Adult ; Child ; Child, Preschool ; Infant ; Hypertension, Pulmonary/epidemiology*

Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC_{50, SMS2} = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t _{1/2, cornea} = 1.11 h; t _{1/2, meibomian glands} = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.

OBJECTIVES: To investigate the inhibitory effect of Zheng GanDecoction (ZGF) on tumor progression in a rat model of diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) and explore the possible mechanism. METHODS: Seventy SD rats were subjected to regular intraperitoneal injections of DEN (50 mg/kg) for 12 weeks to induce HCC tumorigenesis, with another 10 rats receiving saline injections as the normal control. After successful modeling, the rats were randomized into 5 groups (n=10) for daily treatment with distilled water ( model group), Huaier Granules (4 g/kg; positive control group), or ZGF at low, medium, and high doses (2, 4, and 8 g/kg, respectively) via gavage for 17 weeks. Body weight changes of the rats were monitored, and after completion of the treatments, the rats were euthanized for measurement of liver, spleen and thymus indices and morphological and histopathological examinations of the liver tissues using HE staining. The expressions of YAP, p-YAP, MST1, LATS1 and p-LATS1 in the liver tissues were detected using immunohistochemistry and Western blotting. RESULTS: Compared with the normal control rats, the rat models with DEN-induced HCC exhibited much poorer general condition with a significantly reduced survival rate, increased body weight and liver and spleen indices, and a lowered thymus index. ZGF treatment obviously reduced liver and spleen indices, increased the thymus index, and improved pathologies of the liver tissues of the rat models. Immunohistochemistry and Western blotting showed a dose-dependent reduction of YAP expression and an increment of p-YAP expression in ZGF-treated rats, which also exhibited significantly upregulated hepatic expressions of MST1, LATS1 and p-LATS1. CONCLUSIONS ZGF inhibits DEN-induced HCC in rats by activating the Hippo/YAP pathway via upregulating MST1 and LATS1 expression, which promotes YAP phosphorylation and degradation to suppress proliferation and induce apoptosis of the tumor cells.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Diethylnitrosamine ; Rats, Sprague-Dawley ; Rats ; Signal Transduction/drug effects* ; Protein Serine-Threonine Kinases/metabolism* ; Carcinoma, Hepatocellular/drug therapy* ; YAP-Signaling Proteins ; Liver Neoplasms/drug therapy* ; Hippo Signaling Pathway ; Male ; Liver Neoplasms, Experimental/metabolism* ; Transcription Factors/metabolism* ; Adaptor Proteins, Signal Transducing/metabolism*

Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.

Objective To construct a model that can predict the risk of diagnosing ABO-blood group sys-tem hemolytic disease of the newborn(ABO-HDN)and to verify its effectiveness.Methods A total of 446 children with neonatal hyperbilirubinemia who met the inclusion criteria and were first diagnosed in this hos-pital from January 2022 to March 2023 were selected as the modeling group,and were divided into the develo-ping group(200 cases)and the non-developing group(246 cases)according to whether ABO-HDN was diag-nosed.Totally 17 potential influencing factors were included for univariate analysis and multi-factor analysis,and independent risk factors were included in R software to establish a Nomogram model to predict the risk of ABO-HDN.Another 105 cases of neonatal hyperbilirubinemia in the hospital from April to September 2023 were selected as the verification group.Results In the modeling group,Logistic regression analysis showed that maternal pregnancy number,prenatal serum titer,hemoglobin level,white blood cell count,creatine ki-nase level and neonatal Apgar 1 min score were all independent risk factors for ABO-HDN(P＜0.05).Multi-variate Logistic regression analysis showed that the area under receiver operating characteristic(ROC)curve of the modeling group was 0.819(95％CI:0.779-0.859),sensitivity was 0.655,specificity was 0.878.In the verification group,the area under ROC curve was 0.867(95％CI:0.800-0.933),the sensitivity was 0.803,and the specificity was 0.773.Conclusion The established predictive model scoring system can effec-tively predict the risk of ABO-HDN.

Objective To investigate the effects of body weight and length of SD rats on the carotid artery balloon injury-induced vascular stenosis model in order to provide a reference for replicating an ideal vascular stenosis mod-el.Methods Male rats were divided into three groups based on body weight and length.The CONQUEROR? SC PTCA balloon catheter was employed,with a fixed balloon inflation volume of 0.2 mL to induce injury in the left common carotid artery,while the right side served as a control.As soon as surgery operation,one rat from each group was selected for Evans Blue dye verification.Fourteen days later,the injured and contra lateral common ca-rotid arteries from remaining rats were harvested for HE staining to check the extent of stenosis.Based on these find-ings,six rats within the optimal range of body weight and length were selected for further validation.Results Rats with body weights ranging from 280 to 380 g(corresponding body lengths of 21.0-26.5 cm)underwent balloon catheter injury,resulting in endothelial detachment and varying degrees of stenosis in the common carotid artery.In rats weighing 280-300 g(body lengths of 21.0-22.5 cm)had severe stenosis or occlusion of the common carotid artery with thrombosis.In rats weighing 320-340 g(body lengths of 23.0-24.5 cm),the internal and external elastic plates of the common carotid artery were ruptured and the vascular morphology was abnormal.Conversely,rats weighing 360-380 g(body lengths of 25.0-26.5 cm)did not show any ruptured elastic laminae or thrombus formation in the common carotid artery,and the extent of vascular stenos in rats with a body weight of 360 g was moderate and uniform.The results of the repeated validation experiments were consistent.Conclusions Rats with a body weight range of 360 g(corresponding body length of 25.0-26.5 cm)are suitable for development of an ideal vascular stenosis model.

Objective To assess the incidence of contrast-induced nephropathy(CIN)in patients with chronic thromboembolic pulmonary hypertension(CTEPH)after receiving balloon pulmonary angioplasty(BPA),and to evaluate the effect of the contrast agents on renal function.Methods A total of 143 CTEPH patients,who received BPA at the China-Japan Friendship Hospital of China from December 2018 to May 2022,were enrolled in this study.The clinical data,hemodynamic indicators,and serum creatinine(SC)concentrations within one week before and 48-72 h after BPA were collected.The estimated glomerular filtration rate(eGFR)was calculated according to the Modification of Diet in Renal Disease(MDRD)formula.The SC concentration and eGFR changes before and after each BPA procedure were compared.The incidence of CIN and its risk factors were evaluated,and the changes in hemodynamics,SC and eGFR after the initial and last time of BPA treatment were analyzed.Results A total of 192 BPA procedures were performed in 115 CTEPH patients,including 88 BPA procedures in males and 103 BPA procedures in females.The mean amount of contrast agent used for each BPA was(145.58±47.26)mL.After BPA,12 patients developed 13 times of CIN,with an incidence of 6.8％.There was no significant differences(P＞0.05)in the baseline characteristics and SC concentration before BPA between CIN patients and non-CIN patients.In terms of the hemodynamic indexes,the mixed venous oxygen saturation(SvO2)in CIN patients was significantly lower than that in non-CIN patients(58.58％±10.38％vs.66.15％±8.02％,P=0.002),and no statistically significant differences(P＞0.05)in the other hemodynamic indexes existed between CIN group and non-CIN group.No statistically significant differences in SC concentration and eGFR existed before and after each BPA procedure.In patients who had received several BPA procedures,significant improvements in the SC[(78.09±18.760)μmol/L vs.(82.26±21.37)μmol/L,P＜0.001]and eGFR[(86.08±21.22)mL/(min·1.73 m2)vs.(82.07±22.05)mL/(min·1.73 m2),P=0.007]was achieved when compared with their baseline values.Conclusion CTEPH patients may develop CIN after receiving BPA treatment.After receiving several BPA treatments the patient's clinical symptoms and hemodynamics can be improved,and the patient's renal function is also significantly improved.

Background::Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.Methods::We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.Results::The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 ( ERAP1) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1. The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes. Conclusion::The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1. Trial Registration::No. NCT00454519 (https://clinicaltrials.gov/)

Objective To investigate the effect of dapagliflozin on myocardial work and energy metabolism in patients with heart failure with reduced ejection fraction(HFrEF)without type 2 diabetes mellitus(T2DM).Methods Patients with HFrEF without T2DM who visited Wuzhou People's Hospital from January 2021 to January 2022 were randomly divided into conventional group and dapagliflozin group(conventional treatment+dapagliflozin).After treatment(12 months),myocardial work[global work index(GWI),global constructed work(GCW),global wasted work(GW),and global work efficiency(GWE)],energy metabolism[(free fatty acids(FFA)and β-hydroxybutyric acid(β-HB)],traditional cardiac function[left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),and left ventricular ejection fraction(LVEF)],clinical efficacy,prognosis[mortality,rehospitalization,and incidence of major adverse cardiovascular events(MACE)]and adverse reactions were compared between the two groups.Results A total of 128 patients with HFrEF without T2DM were enrolled,including 63 patients in the dapagliflozin group and 65 patients in the conventional group.After treatment,the LVEDD,LVESD,GWW,NT-pro BNP in the dapagliflozin group was significantly lower than that in the conventional group(P＜0.05),while the LVEF,GWI,GCW,GWE,β-HB acid and FFA were significantly higher than those in the conventional group(P＜0.05).The total effective rate and hypoglycemia rates in the dapagliflozin group were significantly higher than those in the conventional group(P＜0.05),and the rehospitalization rate and MACE rate were significantly lower than those in the conventional group(P＜0.05).There were no significant differences in mortality,renal adverse events,urinary tract infections and gastrointestinal symptoms between the two groups(P＞0.05).Conclusion Dapagliflozin has significant clinical efficacy in patients with HFrEF without T2DM,which can increase the serum levels of FFA and ketones,improve effective work,and reduce ineffective work,but it is necessary to be vigilant against hypoglycemia.

Preimplantation genetic testing is an important part in assisted reproductive technology,which can block the intergenerational inheritance of a single gene or chromosomal diseases.Preimplantation genetic testing for polygenic disease risk(PGT-P)is one of the latest developments in the field.With the development of artificial intelligence and genetic detection technology,PGT-P can be used to analyze genetic material,calculate polygenic risk scores and convert these into incidence probability.Embryos with relatively low incidence probability can be screened for transfer,in order to reduce the possibility that the offspring suffers from the disease in the future.This has significant clinical and social significance.At present,PGT-P has been applied clinically and made phased progress at home and abroad.But as a developing technology,PGT-P still has some technical limitations as unstable results,environmental influences and racial differences cannot be ruled out.From the ethical perspective,if the screening indications are not strictly regulated,it is likely to cause new social problems.In this paper,we review the technical details and recent progress in PGT-P,and discuss the prospects of its future development,especially how to establish a complete and suitable screening model for Chinese population.