Objective: To examine the casual association between age at first sexual intercourse and gynecologic malignant tumors using Mendelian randomization (MR) approach. Methods: The single nucleotide polymorphisms (SNPs) associated with age at first sexual intercourse were obtained from a meta-analysis of genome-wide association study (GWAS), and the SNPs related to gynecologic malignant tumors (ovarian cancer, endometrial cancer, cervical cancer), and their subtypes were sourced from the IEU OpenGWAS database. Using age at first sexual intercourse as the exposure and gynecologic malignant tumors as the outcome, a MR analysis was performed with the inverse-variance weighted (IVW) method. Heterogeneity was assessed using Cochran's Q test, horizontal pleiotropy was evaluated using MR-Egger regression and MR-PRESSO test, and bias was examined using funnel plots. Results: The Mendelian randomization analysis demonstrated that younger age at first sexual intercourse was significantly associated with an increased risk of low-grade serous ovarian carcinoma (OR=0.553, 95%CI: 0.335-0.911), cervical cancer (OR=0.674, 95%CI: 0.466-0.974), endometrial cancer (OR=0.854, 95%CI: 0.730-0.999), and endometrioid carcinoma (OR=0.830, 95%CI: 0.690-0.998). No statistical association was found between the age at first sexual intercourse and ovarian cancer, high-grade serous ovarian cancer, mucinous ovarian cancer, endometrioid ovarian cancer, or non-endometrioid ovarian cancer (all P>0.05). Sensitivity analysis showed no evidence of undetected instrumental variable heterogeneity or horizontal pleiotropy (all P>0.05), and the funnel plot indicated no presence of bias. Conclusion Younger age at first sexual intercourse may be associated with an increased risk of certain gynecologic malignant tumors, highlighting the need to strengthen adolescent sex education.

The production of high-quality oocytes requires precisely orchestrated intercellular communication. Extracellular vesicles (EVs) are cell-derived nanoparticles that play a vital role in the transfer of bioactive molecules, which has gained much attention in the field of diagnosis and treatment. Over the past ten years, the participation of EVs in the reproductive processes of oocytes has been broadly studied and has shown great potential for elucidating the intricacies of female reproductive health. This review provides an extensive discussion of the influence of EVs on oocytes, emphasizing their involvement in normal physiology and altered cargo under pathological conditions. In addition, the positive impact of therapeutic EVs on oocyte quality and their role in alleviating ovarian pathological conditions are summarized.
Humans ; Extracellular Vesicles/physiology* ; Oocytes/cytology* ; Female ; Animals ; Cell Communication/physiology*

This study investigated the therapeutic effects and mechanisms of Modified Yiyi Fuzi Baijiang Powder on ulcerative colitis(UC) in rats from the perspective of dampness. SD rats were randomly allocated into six groups(n=10): control, model, mesalazine, and Modified Yiyi Fuzi Baijiang Powder at low(3.96 g·kg~(-1)·d~(-1)), medium(7.92 g·kg~(-1)·d~(-1)), and high(15.84 g·kg~(-1)·d~(-1)) doses. UC was induced in all groups except the control by administration with 3% dextran sulfate sodium(DSS) solution for 7 days. The disease activity index(DAI) was recorded, and the colon tissue was collected for analysis. Histopathological changes were assessed by hematoxylin-eosin staining. Serum levels of D-lactic acid(D-LA) and diamine oxidase(DAO) were measured by ELISA. Immunohistochemistry and PCR were employed to evaluate the expression of aquaporins(AQP3, AQP4) and tight junction proteins [zonula occludens-1(ZO-1) and occludin] at both protein and mRNA levels. Compared with the control group, the model group showed an increased DAI scores(P<0.05), intestinal mucosal damage, elevated serum levels of DAO and D-LA(P<0.05), and decreased expression of AQP3, AQP4, ZO-1, and occludin(P<0.05). Treatment with Modified Yiyi Fuzi Baijiang Powder reduced the DAI scores(P<0.05), lowered the serum levels of D-LA and DAO(P<0.05), and upregulated the expression of AQP3, AQP4, ZO-1, and occludin at both protein and mRNA levels compared with the model group. These findings suggest that Modified Yiyi Fuzi Baijiang Powder exerts therapeutic effects on UC by reducing the intestinal mucosal permeability, promoting colonic mucosal repair, and regulating abnormal intestinal water metabolism, which may involve the upregulation of AQP3 and AQP4 expression.
Animals ; Colitis, Ulcerative/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Intestinal Mucosa/metabolism* ; Male ; Aquaporin 3/metabolism* ; Aquaporin 4/metabolism* ; Permeability/drug effects* ; Humans ; Powders ; Intestinal Barrier Function

OBJECTIVE: To explore the clinical significance of circulating tumor DNA (ctDNA) in response evaluation and relapse monitoring for patients with primary mediastinal large B-cell lymphoma (PMBCL). METHODS: The clinical characteristics, efficacy and survival of 38 PMBCL patients in our hospital from January 2010 to April 2020 were retrospectively analyzed. The ctDNA monitoring was conducted by targeted next-generation sequencing (NGS). RESULTS: Among the 38 patients, 26 cases were female, and 32 cases were diagnosed with Ann Arbor stage I-II. The 5-year overall survival (OS) rate and progression-free survival (PFS) rate were 74.7% and 61.7%, respectively. Males and those with high aaIPI scores (3 points) had a relatively poor prognosis. The NGS results of 23 patients showed that STAT6 (65.2%), SOCS1 (56.5%), and TNFAIP3 (56.5%) were the most common mutated genes. Patients with stable disease (SD)/progressive disease (PD) exhibited enrichment in cell cycle, FoxO, and TNF signaling pathways. A total of 29 patients underwent end-of-treatment PET/CT (EOT PET/CT), and 16 of them received ctDNA monitoring with 12 negative. Among 6 patients with EOT PET/CT positive (Deauville 4), 4 underwent ctDNA monitoring, and 3 of them were negative, being still in continuous remission without any subsequent anti-tumor therapy. CONCLUSION CtDNA may be combined with PET/CT to assess efficacy, monitor relapse, and guide treatment of PMBCL.
Humans ; Circulating Tumor DNA/blood* ; Female ; Mediastinal Neoplasms ; Male ; Retrospective Studies ; High-Throughput Nucleotide Sequencing ; Prognosis ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Middle Aged ; Adult ; Aged ; Neoplasm Recurrence, Local ; Mutation

The liver regenerative capacity is crucial for patients with end-stage liver disease following partial hepatectomy (PHx). The specific bacteria and mechanisms regulating liver regeneration post-PHx remain unclear. This study demonstrated dynamic changes in the abundance of Parabacteroides distasonis (P. distasonis) post-PHx, correlating with hepatocyte proliferation. Treatment with live P. distasonis significantly promoted hepatocyte proliferation and liver regeneration after PHx. Targeted metabolomics revealed a significant positive correlation between P. distasonis and β-hydroxybutyric acid (BHB), as well as hyodeoxycholic acid and 3-hydroxyphenylacetic acid in the gut after PHx. Notably, treatment with BHB, but not hyodeoxycholic acid or 3-hydroxyphenylacetic acid, significantly promoted hepatocyte proliferation and liver regeneration in mice after PHx. Moreover, STAT3 inhibitor Stattic attenuated the promotive effects of BHB on cell proliferation and liver regeneration both in vitro and in vivo. Mechanistically, P. distasonis upregulated the expression of fatty acid oxidation-related proteins, and increased BHB levels in the liver, and then BHB activated the STAT3 signaling pathway to promote liver regeneration. This study, for the first time, identifies the involvement of P. distasonis and its associated metabolite BHB in promoting liver regeneration after PHx, providing new insights for considering P. distasonis and BHB as potential strategies for promoting hepatic regeneration.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

OBJECTIVE: This study reports the first imported case of Lassa fever (LF) in China. Laboratory detection and molecular epidemiological analysis of the Lassa virus (LASV) from this case offer valuable insights for the prevention and control of LF. METHODS: Samples of cerebrospinal fluid (CSF), blood, urine, saliva, and environmental materials were collected from the patient and their close contacts for LASV nucleotide detection. Whole-genome sequencing was performed on positive samples to analyze the genetic characteristics of the virus. RESULTS: LASV was detected in the patient's CSF, blood, and urine, while all samples from close contacts and the environment tested negative. The virus belongs to the lineage IV strain and shares the highest homology with strains from Sierra Leone. The variability in the glycoprotein complex (GPC) among different strains ranged from 3.9% to 15.1%, higher than previously reported for the seven known lineages. Amino acid mutation analysis revealed multiple mutations within the GPC immunogenic epitopes, increasing strain diversity and potentially impacting immune response. CONCLUSION The case was confirmed through nucleotide detection, with no evidence of secondary transmission or viral spread. The LASV strain identified belongs to lineage IV, with broader GPC variability than previously reported. Mutations in the immune-related sites of GPC may affect immune responses, necessitating heightened vigilance regarding the virus.
Humans ; China/epidemiology* ; Genome, Viral ; Lassa Fever/virology* ; Lassa virus/classification* ; Molecular Epidemiology ; Phylogeny

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Yigongsan is derived from Xiaoer Yaozheng Zhijue written by QIAN Yi in the Northern Song dynasty， which is the No. 3 formula in the Catalogue of Ancient Famous Classical Formulas（The Second Batch of Pediatrics） released by the National Administration of Traditional Chinese Medicine（TCM） in September 2022， and it can be developed as a class 3.1 new TCM drug. By referring to ancient medical books and modern literature， this study conducted herbal textual research on Yigongsan from five aspects， including historical evolution， origin and processing， dosage conversion， usage and preparation methods， and functional application， then formed the key information table of this formula， in order to provide reference for the development of reference samples and preparations of Yigongsan. Based on the results of the study， it is recommended that Panax ginseng should be removed the basal part of stem（rhizoma）， Poria cocos should be removed the peel， Citrus reticulata should be cut into shreds and Glycyrrhiza uralensis should be used. According to 4.13 g/Qian（钱）， 1 g/slice for ginger， 3 g for each jujube and 300 mL/Zhan（盏）， the doses of Ginseng Radix， Poria， Atractylodis Macrocephalae Rhizoma， Glycyrrhizae Radix et Rhizoma， Citri Reticulatae Pericarpium， Zingiberis Rhizoma Recens， Jujubae Fructus were 1.652， 1.652， 1.652， 1.652， 1.652， 5， 6 g， and the total amount was 19.26 g. The decocting method was to crush the medicinal materials into fine powder with 50-80 mesh， add 300 mL of water and decoct to 210 mL for each dose， then remove the dregs and take it warmly. This formula was recorded in ancient books as the main treatment for the cold-deficiency of spleen and stomach， and Qi stagnation in children with vomiting and diarrhea and lack of appetite. It has been flexibly applied by later generations of physicians， and is often used to treat anorexia， inflammation of the digestive tract， diarrhea and other diseases in children.