Retrospective analysis of mortality among children under 5 years of age in Huangshi over the period 2002-2022, China.

BACKGROUND: The United Nations' Millennium Development Goals and Sustainable Development Goals both underscore the critical need to reduce the under-five mortality rate globally. China has made remarkable progress in decreasing the mortality rate of children under five. This study aims to examine the trends in child mortality rates from 2002 to 2022 and the causes of deaths among neonates, infants, and children under 5 years of age from 2013 to 2022 in Huangshi. METHODS: The data resource was supported and provided by the Huangshi Health Commission, Huangshi Maternal and Child Health Hospital, and the Huangshi Statistics Bureau. Figures were drawn using Origin 2021. RESULTS: The mortality rate among children under 5 years old significantly decreased, from 21.38 per 1,000 live births in 2002 to 3.53 per 1,000 live births in 2022. The infant mortality rate also saw a significant decline, to 15.06 per 1,000 live births. Among the 1,929 recorded child deaths from 2013 to 2022, the top three causes were: F2 (Disorders related to short gestation and low birth weight), accounting for 17.26% (333 deaths); I1 (Accidental drowning and submersion), for 14.83% (286 deaths); and I3 (Other accidental threats to breathing), for 12.29% (237 deaths). Of the 1,929 deaths, 1,117 were male children, representing 57.91%. The gender disparity in the Under-5 Mortality Rate (U5MR) was calculated to be 1.38 (boys to girls). The leading causes of death under the age of five shifted from F2 (Disorders related to short gestation and low birth weight) to I1 (Accidental drowning and submersion) as children aged, highlighting the need for policymakers and parents to intensify care and vigilance for children. CONCLUSIONS: Huangshi has achieved significant progress in lowering child mortality rates over the past two decades. The study calls for policymakers to enact more effective measures to further reduce the mortality rate among children under 5 years of age in Huangshi. Furthermore, it advises parents to dedicate more time and effort to supervising and nurturing their children, promoting a safer and healthier development.

COVID-19 pandemic amplified mortality rates among adolescents with bipolar disorder through family-related factors.

BACKGROUND: Recently, a growing number of adolescents have been afflicted with mental disorders, with annual morbidity rates on the rise. This trend has been exacerbated by the global coronavirus disease 2019 (COVID-19) pandemic, leading to a surge in suicide and self-harm rates among this demographic. AIM: To investigate the impact of the COVID-19 pandemic on adolescent bipolar disorder (BD), along with the underlying factors contributing to heightened rates of suicide and self-harm among adolescents. METHODS: A comprehensive statistical analysis was conducted utilizing clinical interviews and self-reports obtained from patients or their guardians. Diagnostic criteria for BDs were based on the Diagnostic and statistical manual of mental disorders, international classification of diseases-11, and the National institute of mental health research domain criteria. Statistical analyses were performed using SPSS 26.0 software, with significance set at P < 0.05. RESULTS: A cohort of 171 adolescents diagnosed with BD between January 1, 2018, and December 31, 2022, was included in the analysis. The gender distribution was 2.8:1 (female to male), with ages ranging from 11 to 18 years old. Major factors contributing to adolescent BDs included familial influences, academic stress, genetic predisposition and exposure to school-related violence. Notably, a significant increase in suicide attempts and self-harm incidents was observed among adolescents with BD during the COVID-19 pandemic. Statistical analysis indicated that the pandemic exacerbated familial discord and heightened academic stress, thereby amplifying the prevalence of suicidal behavior and self-harm among adolescents. CONCLUSION: The COVID-19 pandemic has exacerbated familial tensions and intensified the incidence of suicide and self-harm among adolescents diagnosed with BD. This study underscores the urgent need for societal, familial and educational support systems to prioritize the well-being of adolescents and offers valuable insights and guidelines for the prevention, diagnosis and treatment of adolescent BDs.

Application and Progress of Machine Learning in Pesticide Hazard and Risk Assessment.

Long-term exposure to pesticides is associated with the incidence of cancer. With the exponential increase in the number of new pesticides being synthesized, it becomes more and more important to evaluate the toxicity of pesticides by means of simulated calculations. Based on existing data, machine learning methods can train and model the predictions of the effects of novel pesticides, which have limited available data. Combined with other technologies, this can aid the synthesis of new pesticides with specific active structures, detect pesticide residues, and identify their tolerable exposure levels. This article mainly discusses support vector machines, linear discriminant analysis, decision trees, partial least squares, and algorithms based on feedforward neural networks in machine learning. It is envisaged that this article will provide scientists and users with a better understanding of machine learning and its application prospects in pesticide toxicity assessment.

Descriptive and associated risk factors analysis of mental disorders among adolescents in Huangshi, China.

Descriptive analysis of adolescent mental disorders in Huangshi was performed to explore the gender differences, influencing factors, and abnormal illness behaviors. A total of 674 patients in Huangshi Mental Health Center from 2017 to 2022 were collected. A rising trend of mental disorders has been observed since 2018, especially during the COVID-19 pandemic. More young cases led to suicidal attempts and self-harm, which reflects the severity of mental health in adolescents. This study aims to draw the attention of government, society, families, and schools to care about adolescents, which also provides guidance and references for clinical treatment of mental disorders.

p38α/S1P/SREBP2 activation by the SAM-competitive EZH2 inhibitor GSK343 limits its anticancer activity but creates a druggable vulnerability in hepatocellular carcinoma.

Enhancer of zeste homolog 2 (EZH2) mediates epigenetic gene silencing via tri-methylation of histone H3 lysine 27 (H3K27-me3). Increased expression of EZH2 is frequently detected in various cancers including hepatocellular carcinoma (HCC), which is associated with the silencing of tumor suppressor genes. S-adenosyl-L-methionine (SAM)-competitive EZH2 inhibitors fall into the major category of EZH2 inhibitors for cancer therapy. In this study, microarray analyses found that induction of genes related to cholesterol homeostasis is a common effect of SAM-competitive EZH2 inhibitors in cancer cells. As a representative, GSK343 induced lipid accumulation which promoted cancer cell survival. GSK343 selectively activated sterol regulatory element-binding protein 2 (SREBP2), but not SREBP1, in HCC cells. Inhibition of SREBP2 by siRNA reduced cell viability and enhanced the anticancer effect of GSK343. Cancer genomics analysis indicated that SREBP2 upregulation was associated with the poor overall survival of HCC patients. Mechanistically, GSK343-induced SREBP2 activation was unrelated to its original ability to compete with SAM and inhibit EZH2 activity. Instead, GSK343 activated SREBP2 in p38α- and site-1 protease (S1P)-dependent manners. Inhibition of p38α and S1P by SB-202190 and PF-429242, respectively, enhanced the in vitro anticancer activity of GSK343, thereby creating a vulnerability for treating HCC.

In silico and in vitro identification of inhibitory activities of sorafenib on histone deacetylases in hepatocellular carcinoma cells.

Although sorafenib has been approved for treating hepatocellular carcinoma (HCC), clinical results are not satisfactory. Polypharmacology (one drug with multiple molecular targets) is viewed as an attractive strategy for identifying novel mechanisms of a drug and then rationally designing more-effective next-generation therapeutic agents. In this study, a polypharmacological study of sorafenib was performed by mining the next-generation Connectivity Map (CMap) database, CLUE (https://clue.io/). We found that sorafenib may act as a histone deacetylase (HDAC) inhibitor based on similar gene expression profiles. In vitro experimental analyses demonstrated that sorafenib indirectly inhibited HDAC activity in both sorafenib-sensitive and -resistant HCC cells. A cancer genomics analysis using the cBioPortal online tool showed the frequent upregulation of HDAC mRNAs. Furthermore, HCC patients with higher expressions of HDAC1 and HDAC2 had worse overall survival. Taken together, our study suggests that inhibition of HDAC by sorafenib may provide clinical benefits against HCC, and enhancement of HDAC-inhibitory activity of sorafenib may improve its therapeutic efficacy. In addition, our study also provides a novel strategy to study polypharmacology.

In silico and experimental analyses predict the therapeutic value of an EZH2 inhibitor GSK343 against hepatocellular carcinoma through the induction of metallothionein genes.

There are currently no effective molecular targeted therapies for hepatocellular carcinoma (HCC), the third leading cause of cancer-related death worldwide. Enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 (H3K27)-specific methyltransferase, has been emerged as novel anticancer target. Our previous study has demonstrated that GSK343, an S-adenosyl-L-methionine (SAM)-competitive inhibitor of EZH2, induces autophagy and enhances drug sensitivity in cancer cells including HCC. In this study, an in silico study was performed and found that EZH2 was overexpressed in cancerous tissues of HCC patients at both gene and protein levels. Microarray analysis and in vitro experiments indicated that the anti-HCC activity of GSK343 was associated with the induction of metallothionein (MT) genes. In addition, the negative association of EZH2 and MT1/MT2A genes in cancer cell lines and tissues was found in public gene expression database. Taken together, our findings suggest that EZH2 inhibitors could be a good therapeutic option for HCC, and induction of MT genes was associated with the anti-HCC activity of EZH2 inhibitors.

Angiotensin II downregulates ACE2-mediated enhancement of MMP-2 activity in human cardiofibroblasts.

Angiotensin converting enzyme II (ACE2) is a component of the renin-angiotensin system (RAS) that negatively regulates angiotensin II (Ang II). Ang II, in turn, affects the expression of matrix metalloproteinases (MMPs) to induce heart remodeling. The specific mechanisms by which ACE2 regulates MMP-2, however, remain unclear. The aim of this study was to investigate the regulatory relationships between Ang II, ACE2, and MMP-2. ACE2 expression was upregulated and downregulated in human cardiofibroblasts (HCFs) by lentiviral infection. Effects on MMP-2 activity, shed ACE2 activity, extracellular signal-regulated kinase (ERK) signaling pathway, and ADAM metallopeptidase domain 17 (ADAM17) expression were assessed. ACE2 increased MMP-2 activity, and Ang II inhibited this effect through the Ang II type-1 receptor (AT1R) and ERK1/2 signaling pathway. Ang II also reduced the effect of ACE2 on ERK1/2 levels, the activity of shed ACE2, and adam17 expression in HCFs. Additionally, these Ang II-mediated reductions could be attenuated by AT1R antagonist valsartan. In conclusion, these data help to clarify how ACE2 and Ang II interact to regulate MMP-2 and control tissue remodeling in heart disease.

Circulating matrix metalloproteinase-2 and -9 enzyme activities in the children with ventricular septal defect.

Ventricular septal defect (VSD) is the most common form of congenital heart diseases. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases involved in causal cardiac tissue remodeling. We studied the changes of circulating MMP-2 and MMP-9 activities in the patients with VSD severity and closure. There were 96 children with perimembranous VSD enrolled in this study. We assigned the patients into three groups according to the ratio of VSD diameter/diameter of aortic root (Ao). They were classified as below: Trivial (VSD/Ao ratio ≤ 0.2), Small (0.2 < VSD/Ao ≤ 0.3) and Median (0.3 < VSD/Ao) group. Plasma MMP-2 and MMP-9 activities were assayed by gelatin zymography. There was a significant higher MMP-2 activity in the VSD (Trivial, Small and Median) groups compared with that in Control group. The plasma MMP-9 activity showed a similar trend as the findings in MMP-2 activity. After one year follow-up, a significant difference in the MMP-9 activity was found between VSD spontaneous closure and non-closure groups. In conclusion, a positive trend between the severity of VSD and activities of MMP-2 and MMP-9 was found. Our data imply that MMP-2 and MMP-9 activities may play a role in the pathogenesis of VSD.