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.

Aromatherapy refers to the method of using the aromatic components of plants in appropriate forms to act on the entire body or a specific area to prevent and treat diseases. Essential oils used in aromatherapy are hydrophobic liquids containing volatile aromatic molecules， such as limonene， linalool， linalool acetate， geraniol， and citronellol. These chemicals have been extensively studied and shown to have a variety of functions， including reducing anxiety， relieving depression， promoting sleep， and providing pain relief. Terpenoids are a class of organic molecules with relatively low lipid solubility. After being inhaled， they can pass through the nasal mucosa for transfer or penetrate the skin and enter the bloodstream upon local application. Some of these substances also have the ability to cross the blood-brain barrier， thereby exerting effects on the central nervous system. Currently， the academic community generally agrees that products such as essential oils and aromatherapy from aromatic plants have certain health benefits. However， the process of extracting a single component from it and successfully developing it into a drug still faces many challenges. Its safety and efficacy still need to be further verified through more rigorous and systematic experiments. This article systematically elaborated on the efficacy of aromatic substances， including plant extracts and natural small molecule compounds， in antibacterial and antiviral fields and the regulation of nervous system activity. As a result， a deeper understanding of aromatherapy was achieved. At the same time， the potential of these aromatic substances for drug development was thoroughly explored， providing important references and insights for possible future drug research and application.

BACKGROUND: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037). CONCLUSIONS Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Vascular Diseases/etiology* ; Risk Factors ; China/epidemiology* ; Adult ; Proportional Hazards Models ; Cerebrovascular Disorders/epidemiology* ; East Asian People

The disturbance of the human microbiota influences the occurrence and progression of many diseases. Live therapeutic bacteria, with their genetic manipulability, anaerobic tendencies, and immunomodulatory properties, are emerging as promising therapeutic agents. However, their clinical applications face challenges in maintaining activity and achieving precise spatiotemporal release, particularly in the harsh gastrointestinal environment. This review highlights the innovative bacterial functionalized encapsulation strategies developed through advances in physicochemical and biological techniques. We comprehensively review how bacterial encapsulation strategies can be used to provide physical barriers and enhanced adhesion properties to live microorganisms, while introducing superior material properties to live bacteria. In addition, this review outlines how bacterial surface coating can facilitate targeted delivery and precise spatiotemporal release of live bacteria. Furthermore, it elucidates their potential applications for treating different diseases, along with critical perspectives on challenges in clinical translation. This review comprehensively analyzes the connection between functionalized bacterial encapsulation and innovative biomedical applications, providing a theoretical reference for the development of next-generation bacterial therapies.

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective:To explore the genetic etiology for a child with Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 6 (PEOA6).Methods:A child who had attended the Women and Children′s Hospital Affiliated to Ningbo University on 7 August, 2023 was selected as the study subject. Clinical data of the child were analyzed retrospectively. The child and her parents were subjected to whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing and bioinformatic analysis. This study was approved by Medical Ethics Committee of the Women and Children′s Hospital Affiliated to Ningbo University (Ethics No. EC2020-048).Results:The child, a 7-year-old female, had presented with limb muscle pain, amyosthenia, significantly increased creatine kinase, congenital diaphragmatic hernia and recurrent respiratory tract infections. WES revealed that she has harbored a heterozygous c. 1590G>C (p.L530F) variant of the DNA2 gene, which was verified to have a de novo origin by Sanger sequencing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1590G>C was rated as a likely pathogenic variant (PS2+ PM2_Supporting+ PP3). Conclusion:The c.1590G>C (p.L530F) variant of the DNA2 gene probably underlay the PEOA6 in this child.

AIM:To investigate the ameliorative effect of nociceptin/orphanin(N/OFQ)on anxiety-like be-havior in nicotine(NIC)withdrawal-induced rats and its regulatory mechanisms on the expression of neurotransmitters as-sociated with the hypothalamic-pituitary-adrenal(HPA)axis and inflammatory factors.METHODS:Thirty-two adult male Sprague-Dawley rats were randomly divided into 4 groups:normal control group,NIC withdrawal model group,low-dose N/OFQ treatment group,and high-dose N/OFQ treatment group,with 8 rats in each group.To establish NIC with-drawal model,the rats in the NIC model and N/OFQ treatment groups were subcutaneously injected with NIC(0.4 mg/kg),twice a day for 7 consecutive days followed by 3 days of withdrawal.During the withdrawal period,the rats in the low and high-dose N/OFQ treatment groups received intracerebroventricular injection of N/OFQ(1 nmol or 10 nmol)once per day for 3 consecutive days.Ten minutes after the third administration,all rats underwent open filed(OF)and elevated plus maze(EPM)tests to detect behavioral changes.The serum concentrations of corticotrophin-releasing hormone(CRH),adrenocorticotropic hormone(ACTH),corticosterone(CORT),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 were measured by ELISA.The mRNA expression levels of TNF-α,IL-1β and IL-6 in the central nu-cleus of the amygdala(CeA)of the brain were detected by RT-qPCR.Histological changes in neuron morphology in the CA1 region of the hippocampus were observed under a light microscope following hematoxylin and eosin(HE)staining.Norepinephrine(NE)levels in the CeA of the brain were determined by HPLC.The protein expression of tyrosine hydroxy-lase(TH)in the CeA of the brain was detected by Western blot.RESULTS:Compared with the NIC withdrawal model group,rats in the low and high-dose N/OFQ treatment groups showed significant increase in the distance and time spent in the central area of the open field(P<0.05 or P<0.01),as well as significant increase in the number of entries and the per-centage of time spent in the open arms of the EPM(P<0.05 or P<0.01).Furthermore,both low and high-dose N/OFQ treatment groups significantly inhibited serum concentrations of CRH,ACTH and CORT in NIC withdrawal rats(P<0.01).N/OFQ administration also significantly reduced the levels of inflammatory cytokines TNF-α,IL-1β,and IL-6 in the serum,as well as expression levels of TNF-α,IL-1β and IL-6 mRNA in the CeA(P<0.05 or P<0.01).The treatment with N/OFQ at both doses significantly alleviated neuronal damage in the CA1 region of the hippocampus and markedly re-duced thelevels of NE and TH protein expression in the CeA of NIC withdrawal rats(P<0.01).CONCLUSION:N/OFQ alleviates anxiety-like behavior in NIC withdrawal rats through mechanisms related to the regulation of HPA axis hormone levels and inflammatory factors.

Objective To explore the association of epidermal growth factor receptor(EGFR)mutant non-small cell lung cancer(NSCLC)with tyrosine kinase inhibitor(TKI)-related rash based on network pharmacology and to predict the potential traditional Chinese medicine.Methods Gene chip data of EGFR mutant NSCLC cell lines and normal fibroblasts before and after treatment with erlotinib,a TKI,were collected from Gene Expression Omnibus database.Differentially expressed genes were screened using limma package of R 4.3.2 software.Cross-over target genes were screened using venn package.The differentially expressed genes and cross-over target genes were analyzed using ClusterProfiler package.CoreMine Medical database was used to predict traditional Chinese medicine of the cross-over target genes,and the nature,flavour,and channel tropism were analyzed.The results were verified by molecular docking method.Results A total of 126 cross-over target genes were screened.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that the differentially expressed genes and cross-over target genes were enriched in chromosome,spindle and other regions,and were involved in biological processes such as mitosis and DNA replication.These genes were also associated with signaling pathways including DNA replication,lysosomes,and cell cycle.Gene set enrichment analysis results showed that chemokine pathway and nucleotide-binding oligomerization domain-like receptor signaling pathway were activated in the NSCLC cells,and mammalian target of rapamycin signaling pathway and amino acid metabolic pathway were disturbed in the fibroblasts after treatment with erlotinib.CoreMine Medical database predicted that 354 kinds of traditional Chinese medicines were mainly classified as cold,warm and flat,bitter,pungent and sweet,belonging to stomach,lung and liver meridians.Taking Scutellaria baicalensis as an example,molecular docking analysis of experimentally validated target genes and their active components revealed strong binding interactions between the target genes and active components.Conclusion EGFR mutant NSCLC and TKI-related rash have homology in pathogenesis,both involving DNA replication and cell cycle,which provides traditional Chinese medicine medication instruction for patients with EGFR mutant NSCLC and TKI-related rash.

Objective To explore the characteristics of response inhibition of military university students during multitasking operation. Methods Repeated measures of ANOVA as well as distribution test were employed to explore how the performance of 127 military university students in Go/No-Go test was affected by simulated driving task. Results The test results of 127 participants showed that there was a interaction between the interference task and the Go trial proportion on the hit rate and false alarm rate,that is,no significant difference was observed between the 60％ and 40％ of trial proportion without interference task (both P>0.05),but the hit rate and false alarm rate in the 60％ trial proportion condition were significantly higher than those in the 40％ trial proportion condition under interference task (both P<0.01).In addition,significant main effects of interference task were observed on hit rate,false alarm rate,and discrimination index d' (all P<0.01),that is,the interference task reduced the hit rate and discrimination,but increased the false alarm rate.Moreover,individual differences existed in the discrimination index d' changes,and the participants were divided into easily disturbed group (n=23,18.11％),undisturbed group (n=20,15.75％),and intermediate group (n=84,66.14％) by adding or subtracting 1 standard deviation from the mean of the difference. Conclusion The interference tasks increase the psychological load of military university students during multitasking operation,and impair the response inhibition;and individual differences exist in response inhibition.