ObjectiveThis study aims to investigate the molecular mechanism by which Guizhi Fulingwan （GFW） inhibits ferroptosis in endometriosis （EMT） through the regulation of the hypoxia inducible factor-1α/heme oxygenase 1 （HIF-1α/HO-1） signaling pathway. MethodsMachine learning was employed to identify ferroptosis-related biomarkers associated with EMT. Network pharmacology was utilized to identify the active components of GFW and its potential therapeutic targets against EMT， including core targets. Functional enrichment analysis was conducted to explore the biological processes， molecular functions， cellular components， and signaling pathways associated with the potential targets. An EMT rat model was established via autologous transplantation. Thirty female Sprague-Dawley （SD） rats were randomly divided into five groups： sham-operated， model， positive control （dienogest at 0.2 mg·kg^-1）， low-dose GFW （2.5 g·kg^-1）， and high-dose GFW （5 g·kg^-1）. After modeling， the rats received their respective treatment by oral gavage for 28 consecutive days， while the sham and model groups received equal volumes of distilled water. Serum and ectopic endometrial tissues were collected. Hematoxylin and eosin （HE） staining was employed to evaluate morphological alterations in ectopic lesions. Quantitative real-time polymerase chain reaction （Real-time PCR） and Western blot were conducted to assess mRNA and protein expression of HIF-1α， HO-1， glutathione peroxidase 4 （GPX4）， spermidine/spermine N1-acetyltransferase （SAT1）， and prostaglandin-endoperoxide synthase 2 （PTGS2）. Tissue levels of malondialdehyde （MDA）， glutathione （GSH）， and ferrous iron （Fe²⁺） were quantified using commercial assay kits. Serum levels of interleukin-6 （IL-6） and transforming growth factor-β₁ （TGF-β₁） were measured via enzyme-linked immunosorbent assay （ELISA）. ResultsFive ferroptosis-related biomarkers in EMT were identified： ALOX12， CHAC1， SAT1， AST1， and HO-1. Network pharmacology analysis revealed 42 active components of GFW and 192 potential therapeutic target genes related to EMT treatment， with FOS， JUN， HO-1 identified as core targets. Functional enrichment analysis indicated that the potential targets were primarily involved in oxidative stress response and reactive oxygen species metabolism and were enriched in the HIF-1 signaling pathway. Compared to the sham-operated group， the model group exhibited significant increases in both mRNA and protein expression of HIF-1α， HO-1， and PTGS2， as well as elevated tissue levels of Fe²⁺ and MDA. Conversely， GSH levels and the expression of GPX4 and SAT1 were markedly reduced， and serum levels of IL-6 and TGF-β₁ levels were significantly higher （P<0.01）. Compared with the model group， all GFW-treated groups showed significant downregulation of HIF-1α and HO-1， reduced Fe²⁺ levels， and downregulated expression of MDA， PTGS2， IL-6， and TGF-β₁. Meanwhile， GSH， GPX4， and SAT1 expression levels were significantly increased （P<0.05， P<0.01）， effectively ameliorating iron overload and oxidative stress， thereby demonstrating therapeutic efficacy in EMT， with the high-dose GFW demonstrating the most pronounced therapeutic effects. ConclusionGFW exerts therapeutic effects on endometriosis by regulating the HIF-1α/HO-1 signaling pathway to rectify iron metabolism disorders and attenuate free iron-induced oxidative damage. It upregulates the antioxidative defense system to inhibit lipid peroxidation cascades and modulates inflammatory cytokine networks. These effects collectively disrupt the pathological interaction between ferroptosis and chronic inflammation， providing a novel theoretical foundation for the clinical application of GFW in EMT treatment.

Objective: To assess the status of current e cigarette perception and its influencing factors among adolescents in Shanghai, so as to provide reference for the refinement of the prevention and control measures of teenagers e cigarette use. Methods: From May to June 2021, a stratified random cluster sampling was used to investigate 7 456 junior high and high school students in Shanghai. Harm and benefit perception of e cigarette as well as its social environment benefits were collected. Results: The rate of adolescents ever and current e cigarette use was 3.19% and 1.09%, respectively. The top four risk factors for low harm perception of e cigarette were adolescent e cigarette use( OR=2.74, 95%CI =2.10-3.59), high school students ( OR=1.47, 95%CI = 1.32 - 1.64 ), family members ( OR=1.45, 95%CI =1.24-1.70) and friends ( OR=1.36, 95%CI =1.20-1.54) using e cigarette. Adolescent ecigarette use ( OR=2.77, 95%CI =1.97-3.89), high school students( OR=2.11, 95%CI =1.89-2.36), friends ( OR= 1.63, 95%CI =1.42-1.87) and family members using e cigarette( OR=1.39, 95%CI =1.18-1.65) were the top four associated factors for high benefit perception of e cigarette. And, adolescent e cigarette use ( OR=1.95, 95%CI =1.47-2.59), high school students ( OR= 1.73, 95%CI =1.55-1.93), friends ( OR=1.60, 95%CI =1.40-1.82) and pocket money≥200 yuan using e cigarette( OR= 1.29 , 95%CI =1.17-1.43) were the top four risk factors for high social environmental benefit perception of e cigarette. Moreover, perception of e cigarette harm, benefit and social environmental benefit were associated with the risk of future use of e cigarette( OR = 0.78,1.44,1.21, P <0.01). Conclusion Being high school students and using e cigarette by oneself, friends, and family members are the important influencing factors for adolescents e cigarette perception. Both low harm and high benefit perception of e cigarette elevate the risk of future e cigarette use among adolescents, so effective measures should be taken to promote control education about e cigarette and smoke free environment construction.

Background Mitochondrial dynamin-related protein 1 (DRP1) regulates mitochondrial division and plays an important role in maintaining hepatocyte function. However, the role of DRP1 in cadmium exposure-induced maternal liver damage in pregnant mice remains unclear. Objective To investigate the role and mechanism of DRP1 in maternal liver damage induced by cadmium exposure during pregnancy. Methods This study consisted of animal experiments and cell experiments. (1) Animal experiments. Mice at 14 days of gestation were randomly divided into three groups: a control group, a low-dose cadmium group (LCd group: 2.5 mg·kg⁻¹), and a high-dose cadmium group (HCd group: 5 mg·kg⁻¹). The pregnant mice were intraperitoneally injected with cadmium chloride (CdCl₂) for 6 and 24 h in the next morning. The weights of pregnant mice, uterus, maternal liver, and fetal mice were recorded after sacrifice. Serum and liver of pregnant mice were collected, the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were detected, and liver tissues were stained with HE to observe changes in liver function and liver tissue structure. The expressions of oxidative phosphorylation-related proteins, hypoxia inducible factor-1α (HIF-1α) and DRP1 proteins in liver of pregnant mice were detected by Western blotting. (2) Cell experiments. AML12 cells were treated with CdCl₂ (10 μmol·L⁻¹) for 0, 2, 6, 12, and 24 h. The expressions of oxidative phosphorylation-related proteins, DRP1, and hypoxia inducible factor-1α (HIF-1α) proteins were detected. AML12 cells were pretreated with DRP1 inhibitor Mdivi-1 for 1 h and then CdCl₂ (10 μmol·L⁻¹) for 12 h to detect the expression of oxidative phosphorylation-related proteins and DRP1 protein. AML12 cells were treated with Hif-1α siRNA for 48 h and CdCl₂ (10 μmol·L⁻¹) for 6 h to detect the expression of HIF-1α and DRP1 proteins. Results The results of animal experiments showed that cadmium exposure in pregnant mice had no effects on maternal liver weight and liver coefficient. However, the histomorphological changes and necrosis in hepatocytes were observed. Compared with the control group, the serum ALT and AST levels of pregnant mice in the LCd group were significantly increased after 6 h (P＜0.05), and the levels in the HCd group were significantly increased after 6 and 24 h (P＜0.05). Cadmium exposure during pregnancy significantly up-regulated HIF-1α and DRP1 expressions and down-regulated the expressions of oxidative phosphorylation-related proteins in maternal livers. In vitro cell experiments showed that the expressions of oxidative phosphorylation-related proteins was significantly decreased and HIF-1α and DRP1 protein expressions were significantly increased in the AML12 cells treated with CdCl₂ for 6 h. Mdivi-1 pretreatment significantly antagonized the inhibitory effect of cadmium on the expressions of oxidative phosphorylation-related proteins in AML12 cells, while Hif-1α siRNA pretreatment significantly antagonized the up-regulative effect of cadmium on DRP1 expression in AML12 cells. Conclusion Cadmium exposure in pregnant mice may up-regulate DRP1 expression by activating HIF-1α signaling, then inhibit oxidative phosphorylation level of hepatic cells, and ultimately lead to maternal liver damage.

Objective:To explore the clinical and pathological characteristics and prognostic factors of gastric neuroendocrine carcinoma(G-NEC)and gastric mixed adenoendocrine carcinoma(G-MANEC).Methods:Retrospective analysis was conducted on the clinical data of 67 patients with G-NEC and G-MANEC who underwent surgical treatment at Heping Hospital Affiliated to Changzhi Medical College from May 2015 to May 2023.The study included an analysis of the pathological characteristics distinguishing G-NEC from G-MANEC.Results:Com-pared to gastric adenocarcinoma,patients with G-NEC and G-MANEC in the stomach showed a higher incidence of gastric cancer in the male gastric cardia and were diagnosed at a later age.Tumors with larger diameters increase susceptibility to anemia,low albumin levels,and in-vasion of nerves and vasculature.Deeper tumor infiltration is associated with increased local lymph node metastases,later TNM staging,and a higher likelihood of distant metastasis post-surgery.The prognosis of G-NEC and G-MANEC is worse than that of gastric adenocarcinoma(P=0.001).However,there is no statistically significant difference in the pathological characteristics(P>0.05)and prognosis analysis(P=0.212)between G-NEC and G-MANEC.Univariate survival analysis identified age,preoperative albumin,preoperative CEA,number of lymph node metastases,TNM staging,and postoperative distant metastasis as risk factors affecting patient's overall survival(OS).In the multivariate ana-lysis,age,preoperative albumin,TNM staging,and postoperative distant metastasiswere identified as independent risk factors for OS.Con-clusions:There is a significant difference in clinical characteristics between G-NEC,G-MANEC,and gastric adenocarcinoma,often diagnosed at an advanced stage,which is prone to distant metastasis post-surgery.Poor prognosis is observed in patients aged over 60 years,with pre-operative albumin<40g/L,TNM stage Ⅱ/Ⅲ,and postoperative distant metastasis.

In recent years, with the vigorous marketing of e-cigarette manufacturers, e-cigarettes have become a popular tobacco product for adolescents. The problem of e-cigarette environmental exposure among adolescents is also getting worse and its associated adverse impacts cannot be ignored. However, domestic research on the environmental exposure to e-cigarettes among youth is insufficient, and experience on e-cigarette regulation is also limited. This review first briefly introduced the definition and sources of e-cigarette environment exposure, then focused on the differences of e-cigarette environmental exposure among adolescents with different characteristics to identify possible influencing factors, as well as the impacts of e-cigarette environmental exposure on adolescents, and finally summarized international countermeasures to prevent e-cigarette environmental exposure in adolescents, aiming to provide directional guidance for China to conduct e-cigarette control activities among adolescents.

Adverse childhood experience (ACE) is potentially negative experience that occurs between 0 and 18 years old. The ACE adolescents have prominent mental health problems such as emotional regulation disorder, unstable interpersonal relationship, poor coping ability, and cognitive dysfunction. Until now, the factors affecting the mental health of ACE adolescents are not clear, but it is certain that the ecosystem in which ACE adolescents life affects their mental health. Specifically, the parent-child relationship, the school environment, the peer relationship in the micro-system, and the interaction between the parent-child relationship and other interpersonal relationship in the meso-system have been confirmed to be significantly related to the mental health of ACE adolescents. In the appearance system, the neighborhood cohesion, the level of family income, the educational level of parents and the different social and cultural background in the macro-system all have different degrees of impact on the development of ACE adolescents' psychological behaviors. In the diachronic system, the time and frequency of suffering from ACE have different effects on the mental health regarding the ACE adolescents.
Adolescent ; Adverse Childhood Experiences ; Child ; Child, Preschool ; Ecosystem ; Health Status ; Humans ; Infant ; Infant, Newborn ; Mental Health ; Parents

Objective : To investigate the spatial distribution and the influencing factors of hypertensive patients aged 45 years and above,and to provide evidence for the prevention and control of hypertension among middle-aged and elderly population. Methods : Multi-stage stratified random sampling method was used to collect 150 counties（cities or districts）from 30 provinces（municipalities or autonomous regions）from CHARLS database in 2015 according to the per capita GDP in different areas. Then the probability proportionate to size sampling method was used to select three villages（neighborhood committees）,80 families were randomly selected from each village（neighborhood committees）,and residents aged 45 years and above were interviewed. Spatial analysis was based on the vector map of China's provincial boundaries,Geoda and ArcGIS 10.2 software were used to analyze the prevalence and influencing factors of hypertension at provincial levels. Results : The health data of 14 880 people aged 45 years and above in 28 provinces（municipalities or autonomous regions）were obtained,including 4 203 patients with hypertension（28.25%）and 5 408 people with pre-hypertension（36.34%）. The results of local spatial analysis showed that the clustering regions of hypertension patients were in northeast and eastern parts of China. The results of spatial regression analysis showed that males,age of 80 years and above and overweight were the main risk factors for hypertension（all P<0.05）,which had greater influence on the middle part of China,north and northeast of China,and the east and north of China,respectively. Conclusion Males,age of 80 years and above and overweight were the main risk factors for hypertension in middle-aged and elderly population in China. The main prevention and control areas of hypertension were eastern and northeast China.

Objective To investigate the relationship between total cerebral small vessel disease (CSVD) burden and intracranial hemorrhage transformation (HT) after intravenous thrombolysis in patients with acute ischemic stroke (AIS).Methods One hundred and fifty-four patients who suffered from ischemic stroke within 4.5 hours of onset and received recombinant tissue plasminogen activator thrombolytic therapy in the emergency green channel of the First Affiliated Hospital of Soochow University from August 2016 to January 2018 were enrolled.HT examined by computed tomography scan within 24 hours after thrombolysis was included.The magnetic resonance imaging examination was performed within 48 hours.The patients were divided into two groups:HT group and control group according to the presence or absence of HT.Periventricular white-matter hyperintensities (WMH) with Fazekas score of 3 or deep WMH with Fasekas score of 2 or 3 was recorded as 1 point,MRI of cerebral microbleeds (CMBs) or lacunar infarction (LI) was recorded as 1 point respectively,and peripheral vascular space (PVS) in basal ganglia graded 2-4 (≥11)was counted 1 point.Single-factor analysis was used to compare total CSVD burden score,baseline data and clinical data between the two groups.Multivariate Logistic regression analysis was performed to explore the relationship between total CSVD burden score and HT.Results The age of the 154 patients was 66.00(59.00,74.25) years,males accounted for 66.9％ (103/154),onset to treatment time (OTT) was 174.50 (131.50,200.00) minutes and the NIHSS score before thrombolytic therapy was 6.00 (3.00,10.25).There were 43 cases (27.9％) with moderate to severe WMH,35 cases (22.7％) with CMBs,52 cases (33.8％) with PVS graded 2-4,and 96 cases (62.3％) with LI.There were 21 enrolled patients (13.6％) who suffered from HT.Symptomatic intracranial hemorrhage occurred in nine cases (5.8％).In the multivariate Logistic regression model,the results demonstrated that baseline diastolic pressure (OR=1.072,95％CI 1.027-1.118,P=0.001)and atrial fibrillation (OR=28.564,95％CI 6.217-131.241,P=0.000) were independently associated with HT.After using the mild CSVD burden score as a reference,moderate CSVD burden (OR=0.810,95％ CI 0.154-4.257,P=0.804) was not associated with HT after thrombolysis,and severe CSVD burden (OR=8.429,95％ CI 1.643-43.227,P=0.011) was independently associated with HT.Conclusions The severity of total CSVD burden in patients with AIS was closely related to HT after thrombolysis.Severe CSVD was an independent risk factor for HT after thrombolysis.

We propose a computational workflow (I3) for intuitive integrative interpretation of complex genetic data mainly building on the self-organising principle. We illustrate the use in inter-preting genetics of gene expression and understanding genetic regulators of protein phenotypes, particularly in conjunction with information from human population genetics and/or evolutionary history of human genes. We reveal that loss-of-function intolerant genes tend to be depleted of tissue-sharing genetics of gene expression in brains, and if highly expressed, have broad effects on the protein phenotypes studied. We suggest that this workflow presents a general solution to the challenge of complex genetic data interpretation. I3 is available at http://suprahex.r-forge.r-pro-ject.org/I3.html.

The development of neuroimaging has led to a high diagnostic rate of cerebral small vessel disease (CSVD).The hemorrhage transformation (HT) and clinical prognosis after intravenous thrombolysis in acute ischemic stroke (AIS) with CSVD have become hot topics in recent years.Relevant studies have shown that different subtypes of CSVD may have different influences in HT and clinical prognoses in AIS.In clinic,each subtype of CSVD may not exist alone in one patient,therefore,some scholars put forward the concept of total burden of CSVD to further quantitatively assess the severity of CSVD in the whole brain and their effects on HT and clinical prognosis after intravenous thrombolysis of AIS.This article reviews the researches on HT and clinical prognosis after intravenous thrombolysis in AIS with CSVD.