OBJECTIVES: To investigate the role and mechanism of fibroblast growth factor (FGF) 19 in inflammation-induced injury of vascular endothelial cells caused by high glucose (HG). METHODS: Human umbilical vein endothelial cells (HUVECs) were randomly divided into four groups: control, HG, FGF19, and HG+FGF19 (n=3 each). The effect of different concentrations of glucose and/or FGF19 on HUVEC viability was assessed using the CCK8 assay. Flow cytometry was utilized to examine the impact of FGF19 on HUVEC apoptosis. Levels of interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), total superoxide dismutase (T-SOD), and malondialdehyde (MDA) were measured by ELISA. Real-time quantitative PCR and Western blotting were used to determine the mRNA and protein expression levels of vascular endothelial growth factor (VEGF), nuclear factor erythroid 2 related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Cells were further divided into control, siRNA-Nrf2 (siNrf2), HG, HG+FGF19, HG+FGF19+negative control, and HG+FGF19+siNrf2 groups (n=3 each) to observe the effect of FGF19 on oxidative stress injury in HUVECs induced by high glucose after silencing the Nrf2 gene. RESULTS: Compared to the control group, the HG group exhibited increased apoptosis rate, increased IL-6, iNOS and MDA levels, and increased VEGF mRNA and protein expression, along with decreased T-SOD activity and decreased mRNA and protein expression of Nrf2 and HO-1 (P<0.05). Compared to the HG group, the HG+FGF19 group showed reduced apoptosis rate, decreased IL-6, iNOS and MDA levels, and decreased VEGF mRNA and protein expression, with increased T-SOD activity and increased Nrf2 and HO-1 mRNA and protein expression (P<0.05). Compared to the HG+FGF19+negative control group, the HG+FGF19+siNrf2 group had decreased T-SOD activity and increased MDA levels (P<0.05). CONCLUSIONS FGF19 can alleviate inflammation-induced injury in vascular endothelial cells caused by HG, potentially through the Nrf2/HO-1 signaling pathway.
Humans ; NF-E2-Related Factor 2/genetics* ; Signal Transduction ; Human Umbilical Vein Endothelial Cells/drug effects* ; Fibroblast Growth Factors/pharmacology* ; Heme Oxygenase-1/physiology* ; Apoptosis/drug effects* ; Glucose ; Inflammation ; Interleukin-6/analysis* ; Vascular Endothelial Growth Factor A/genetics* ; Nitric Oxide Synthase Type II/analysis* ; Cells, Cultured

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Drug-induced liver injury (DILI) is one of the most common adverse drug reactions that may seriously threaten the health of children and is receiving increasing clinical attention day by day. There is still no independent diagnosis and treatment guideline for DILI in children, but its clinical features are not completely similar to those in adults. This article reviews the epidemiology, clinical features, diagnosis, and treatment progress in order to provide a reference for the management of DILI in children.
Child ; Humans ; Chemical and Drug Induced Liver Injury/therapy* ; Drug-Related Side Effects and Adverse Reactions ; Liver/pathology* ; Risk Factors

Drug-induced liver injury (DILI) risk prediction, diagnosis establishment, clinical management, and all other aspects are facing great challenges. Although the current understanding of its pathogenesis is still incomplete, research over the past 20 years has shown that genetic susceptibility may play an important role in the occurrence and development of DILI. In recent years, pharmacogenomics studies have further revealed the association between human leukocyte antigen (HLA) genes, some non-HLA genes, and hepatotoxicity from certain drugs. However, due to the lack of well-designed, prospective, large-sample cohort validation and low positive predictive values, there may still be some way to go before the current results can be truly translated into clinical practice for precise prediction and prevention of DILI risk.
Humans ; Genetic Predisposition to Disease ; Prospective Studies ; Risk Factors ; Chemical and Drug Induced Liver Injury/genetics* ; Drug-Related Side Effects and Adverse Reactions ; Liver

Drug-induced liver injury (DILI) is an important adverse drug reaction that can lead to acute liver failure or even death in severe cases. Currently, the diagnosis of DILI still follows the strategy of exclusion. Therefore, a detailed history taking and a thorough and careful exclusion of other potential causes of liver injury is the key to correct diagnosis. This guideline was developed based on evidence-based medicine provided by the latest research advances and aims to provide professional guidance to clinicians on how to identify suspected DILI timely and standardize the diagnosis and management in clinical practice. Based on the clinical settings in China, the guideline also specifically focused on DILI in chronic liver disease, drug-induced viral hepatitis reactivation, common causing agents of DILI (herbal and dietary supplements, anti-tuberculosis drugs, anti-neoplastic drugs), and signal and assessment of DILI in clinical trials.
Humans ; Chemical and Drug Induced Liver Injury/therapy* ; Drug-Related Side Effects and Adverse Reactions ; Liver Failure, Acute ; Dietary Supplements/adverse effects* ; Risk Factors

Humans ; Arthroplasty, Replacement, Knee/adverse effects* ; Surgical Wound Infection/etiology* ; Retrospective Studies ; Risk Factors ; Arthroplasty, Replacement, Hip/adverse effects* ; Prosthesis-Related Infections/etiology*

OBJECTIVES: To study the features of catheter-related bloodstream infection (CRBSI) or central line-associated bloodstream infection (CLABSI) after peripherally inserted central catheterization (PICC) in neonates admitted to the neonatal intensive care unit (NICU) and the risk factors for CRBSI or CLABSI. METHODS: A retrospective analysis was performed on the medical data of the neonates who were treated and required PICC in the NICU of the Children's Hospital, Zhejiang University School of Medicine from June 1, 2018 to May 1, 2020. The catheterization-related data were collected, including placement time, insertion site, removal time, and antimicrobial lock of PICC. The multivariate logistic regression model was used to investigate the risk factors for CRBSI or CLABSI in the neonates. RESULTS: A total of 446 neonates were enrolled, with a mean gestational age of (30.8±4.0) weeks, a mean birth weight of (1 580±810) g, a median age of 9 days, and a median duration of PICC of 18 days. The incidence rates of CLABSI and CRBSI were 5.6 and 1.46 per 1 000 catheter days, respectively. Common pathogens for CLABSI caused by PICC included Staphylococcus epidermidis (n=19) and Klebsiella pneumoniae (n=11), and those for CRBSI caused by PICC included Klebsiella pneumoniae (n=6). The risk of CLABSI caused by PICC increased significantly with prolonged durations of PICC and antibiotic use, and the PICC-related infection probability at head and neck was significantly lower than that in the upper and low limbs (P<0.05), while the above conditions were more obvious in neonates with a birth weight of <1 500 g. The risk of CRBSI caused by PICC decreased with the increase in gestational age (P<0.05). CONCLUSIONS CRBSI and CLABSI remain serious issues in NICU nosocomial infection. The identification of the risk factors for CRBSI and CLABSI provides a basis for improving the quality of clinical care and management.
Catheter-Related Infections/etiology* ; Catheterization, Central Venous/adverse effects* ; Catheterization, Peripheral/adverse effects* ; Central Venous Catheters/adverse effects* ; Child ; Humans ; Infant ; Infant, Newborn ; Retrospective Studies ; Risk Factors ; Sepsis/etiology*

Objective: To investigate the associations between adverse childhood experiences (ACE) and substance use behaviors among lesbians to provide a scientific basis for high-risk population identification and formulation of targeted intervention measures. Methods: Lesbians who participated in routine AIDS voluntary counseling, testing services, activities, and peer recommendations were recruited from July to December 2018, with the help of LesPark in Beijing. Convenient sampling method was used. Demographic characteristics, ACE, and substance use behaviors of subjects were investigated using an online platform powered by www.wjx.cn. Subsequently, the associations between ACE and adulthood substance use behaviors were evaluated using the logistic regression model. The SPSS 22.0 was used for statistical analysis. Results: A total of 294 lesbians were recruited in the study, 81.3% (239/294) of them were lesbians, and 18.7% (55/294) were bisexuals. Besides, 55.8% (164/294) of subjects reported they had had ACE, with proportions of lesbians experiencing abuse, neglect, and family dysfunction as 33.3% (98/294), 24.5% (72/294), and 32.7% (96/294), respectively. 55.1% (162/294) of the lesbians reported they had smoked in the past 30 days, 11.2% (33/294) reported having drug-use behavior in the past three months, and 22.8% (67/294) claimed drinking alcohol weekly. Multivariate logistic regression analysis showed that lesbians with ACE were at high risks to smoke (OR=1.87, 95%CI: 1.13-3.08), drink (OR=2.13, 95%CI: 1.18-3.84), and use drugs (OR=3.33, 95%CI: 1.29-8.61) in adulthood. Moreover, lesbians with childhood family dysfunction were at higher risk of smoking cigarettes (OR=2.60, 95%CI: 1.46-4.62) and drinking alcohol (OR=2.65, 95%CI: 1.44-4.87). At the same time, those with abuse experience were at higher risk of drug use (OR=3.17, 95%CI: 1.26-7.96). Conclusions: Substance use behaviors, including cigarette smoking, drinking alcohol, and drugs use, were common among lesbians. Positive associations were found between ACE and adulthood substance use behaviors.
Adult ; Adverse Childhood Experiences ; Child ; Child Abuse/psychology* ; Female ; Humans ; Risk Factors ; Sexual and Gender Minorities ; Substance-Related Disorders/psychology*

BACKGROUND: Few studies have explored the modifications by family stress and male gender in the relationship between early exposure to traffic-related air pollution (TRAP) and allergic rhinitis (AR) risk in preschool children. METHODS: We conducted a case-control study of 388 children aged 2-4 years in Shenyang, China. These children AR were diagnosed by clinicians. By using measured concentrations from monitoring stations, we estimated the exposures of particulate matter less than 10 μm in diameter (PM RESULTS: The prevalence of AR in children aged 2-4 years (6.4%) was related to early TRAP exposure. With an IQR (20 μg/m CONCLUSIONS Family stress and male gender may increase the risk of AR in preschool children with early exposure to PM
Air Pollution/adverse effects* ; Case-Control Studies ; Child, Preschool ; China/epidemiology* ; Cities ; Family/psychology* ; Female ; Humans ; Male ; Prevalence ; Rhinitis, Allergic/epidemiology* ; Risk Factors ; Stress, Psychological/complications* ; Traffic-Related Pollution/adverse effects*

BACKGROUND: Substance abuse is a worldwide problem that primarily affects adolescents, resulting in chronic health complications as well as psychosocial challenges and economic losses. However, the magnitude of the problem and the factors that contribute to it are not well studied in Ethiopia, particularly in the study area. As a result, this study was carried out to determine the prevalence and associated factors of substance use among preparatory school students in the Kolfe-Keraniyo sub-city of Addis Ababa, Ethiopia. METHODOLOGY: An institution-based cross-sectional study of 383 randomly selected preparatory school students in the Kolfe-Keraniyo sub-city was conducted. The data were gathered using a pretested self-administered structured questionnaire. Multivariable binary logistic regression analysis was employed to identify factors associated with substance use based on the adjusted odds ratio (AOR) and 95% confidence interval (CI) with p values less than 0.05. RESULT: This study revealed that the lifetime prevalence of substance use among preparatory students in Kolfe-Keraniyo sub-city, Addis Ababa, Ethiopia, was 26.5% (95% CI, 22.2, 30.7%). Specifically, 16% drunk alcohol, 9.6% smoked cigarette, and 9.4% chewed khat. The 16.3% were current users, of which 8.3% were drinkers, 6.4% were smokers, and 5.9% were khat chewers. Substance use was significantly associated with being male (AOR, 3.3; 95% CI, 1.284, 8.613), having alcohol drinking family member (AOR, 4.0; 95% CI, 1.704, 9.196), having khat chewing family member (AOR, 2.87; 95% CI, 1.161, 7.070), poor school substance use controlling rule (AOR, 6.64; 95% CI, 1.863, 23.687), availability of substance retailing shops in residential areas (AOR, 2.9; CI, 1.303, 6.606), strong relationship with parents (AOR, 0.005; 95% CI, 0.001, 0.026), and being member of school mini-media (AOR, 0.177; 95% CI, 0.048, 0.657). CONCLUSION According to the findings of this study, one-quarter of the study participants were substance users. Alcohol, khat, and cigarettes were all commonly used substances. Gender, parent-child relationship, family member substance use history, school substance use controlling rules, school mini-media and pro-social involvement, and the availability of substance retailing shops were all strongly associated with substance use. Strengthening school rules on substance use, controlling substance retailing shops near schools and residential areas, and providing students with health education are all strategies for reducing substance use among students.
Adolescent ; Cross-Sectional Studies ; Ethiopia/epidemiology* ; Female ; Humans ; Male ; Prevalence ; Risk Factors ; Schools ; Students/statistics & numerical data* ; Substance-Related Disorders/epidemiology* ; Surveys and Questionnaires ; Young Adult