OBJECTIVES: To investigate the molecular mechanism by which He's Yangchao Formula improves ovarian function in premature ovarian insufficiency (POI) mice through intestinal flora modulation. METHODS: Forty female ICR mice (aged 6-8 weeks) were intraperitoneally injected with cyclophosphamide (150 mg/kg) to establish a POI model, while 10 untreated mice served as the blank control. Successfully modeled mice were randomly divided into four groups (n=10/group): low-dose He's Yangchao Formula (6 g crude herb/kg), high-dose He's Yangchao Formula (25 g crude herb/kg), positive control (estradiol), and model control (distilled water). Treatments were admin-istered daily by gavage for 6 weeks. Vaginal exfoliated cells were stained with Wright-Giemsa solution to monitor estrous cycles. Serum estradiol and follicle-stimulating hormone (FSH) levels were measured by ELISA. Ovarian FSH receptor (FSHR) expression was assessed by immunohistochemistry. Glycolysis-related proteins pyruvate kinase M2 (PKM2) and glucose transporter 4 (GLUT4) were analyzed by Western blotting and immuno-fluorescence. Fecal samples from blank control, model control, and high-dose groups underwent metagenomic sequencing to evaluate intestinal microbiota diversity and com-position. RESULTS: He's Yangchao Formula restored estrous cyclicity, increased serum estradiol (P<0.05), decreased serum FSH (P<0.05), and upregulated FSHR expression in granulosa cells (P<0.05). Metagenomic analysis revealed significant structural differences in intestinal flora among blank control, model control, and high-dose groups (P<0.01). The high-dose group showed reduced abundance of conditional pathogens (e.g., Alistipes, Prevotella, Odoribacter, Blautia, Rikenella) compared to the model control (P<0.05). Functional enrichment analysis indicated involvement of glycolysis-related pathways. Concordantly, PKM2 and GLUT4 expression was downregulated in the model control but upregulated in He's Yangchao Formula groups (P<0.05). CONCLUSIONS He's Yangchao Formula ameliorates POI in mice by remodeling intestinal flora structure, enhancing glycolytic activity, improving ovarian sex hormone secretion, increasing granulosa cell FSHR expression, and restoring estrous cyclicity.

OBJECTIVES: To investigate the molecular mechanism by which He's Yangchao Decoction (HSYC) improves ovarian function in a mouse model of premature ovarian insufficiency (POI). METHODS: Forty ICR mice were used to establish a POI model via intraperitoneal injection of cyclophosphamide and were randomly assigned to four groups: model control group, low-dose HSYC group, high-dose HSYC group, and estradiol group (positive control). Additionally, 10 age-matched ICR mice were selected as the blank control group. After intragastric intervention, the ovarian index, serum follicle-stimulating hormone (FSH) levels, and ovarian tissue expression of the FSH receptor (FSHR) were measured. A POI cell model was established by treating the human granulosa tumor cell line (KGN) with 4-hydroxycyclophosphamide. The cells were divided into four groups: solvent control group, HSYC group, inhibitor control group, and inhibitor+HSYC group, which were respectively treated with TH5487 (an OGG1 inhibitor) and HSYC-containing serum. The expressions of OGG1, mitochondrial DNA (mtDNA) oxidative damage markers, and pyroptosis-related proteins were detected by molecular docking, Western blotting, and immunofluorescence. RESULTS: Compared with the blank control group, the model control group showed a decreased ovarian index (P<0.05) and increased serum FSH levels (P<0.01). The ovarian index was higher in both the low- and high-dose HSYC groups compared with the model control group (both P<0.05). FSHR expression in ovarian tissue was lower in the model control group than that in the blank control group, but was higher in the high-dose HSYC group compared with the model control group (P<0.05 or P<0.01). Molecular docking confirmed strong binding affinity between the active components of HSYC and OGG1 (binding energy: －6.3 to －8.3 kcal/mol). Western blotting analysis revealed that OGG1 protein expression in the ovaries of the model control group was significantly reduced compared with the blank control group, while it was increased in the low-dose HSYC group and the estradiol group (P<0.05 or P<0.01). Immunofluorescence results demonstrated that the expression levels of mito-chondrial transcription factor A (TFAM) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) were decreased in the model control group compared with the blank control group (P<0.01), whereas their expressions were significantly elevated in the high-dose HSYC group and the estradiol group (all P<0.01). Cell experiments showed that TH5487 intervention increased the expression of 8-oxoguanine (8-OxoG) (P<0.01), while HSYC-containing serum intervention reduced 8-OxoG expression and increased TFAM expression (P<0.01). The expression of pyroptosis-related proteins (GSDMD, N-GSDMD, caspase-1, IL-1β) increased after TH5487 intervention (P<0.05), whereas HSYC-containing serum suppressed their expression (all P<0.05). CONCLUSIONS HSYC improves POI by upregulating OGG1 expression, mitigating mtDNA oxidative damage, and inhibiting granulosa cell pyroptosis.

Objective:To evaluate the efficacy and safety of Chinese medicine Jianpi Antai formula in infertile women undergoing in vitro fertilization-embryo transfer(IVF-ET).Methods:A total of 300 infertile women who underwent 2 frozen embryo transfer procedures at the Reproductive Medicine Center,Sir Run Run Shaw Hospital were included in the study.The participants were randomly divided into study group and control group.The study group received routine medication plus the Jianpi Antai formula during the period of embryo transfer,while the control group received routine medication only.The general condition,embryo implantation rate,clinical pregnancy rate,live birth rate,and the blood routine and liver and kidney function were evaluated and compared between two groups.Results:There were 277 cases who completed the study,including 134 in the study group and 143 in the control group.The embryo implantation rate(68.7%vs.55.9%),the clinical pregnancy rate(56.7%vs.44.8%)and the live birth rate(50.7%vs.37.8%)in the study group were all higher than those in the control group(all P＜0.05).Subgroup analysis revealed that in patients of advanced age(≥35 years)and those with decreased ovarian reserve function(anti-Müllerian hormone＜1.68 ng/mL),the embryo implantation rate,clinical pregnancy rate,and live birth rate in the study group were all higher than those in the control group(all P＜0.05).During the follow-up period,there were no abnormalities in the basic vital signs of both groups,and no adverse events were reported.Conclusion:Jianpi Antai formula can safely improve the embryo implantation rate in infertile women undergoing IVF-ET,reduce the embryo miscarriage rate,increase the live birth rate as well as improve the clinical outcomes.

Objective:To investigate the effect of Chinese medicine He's Yangchao recipe on premature ovarian insufficiency(POI)and its relationship with mitochondrial function of ovarian granulose cells in an animal model.Methods:Thirty-six female C57BL/6J mice were randomly divided into blank control group,model group,low-,medium-and high-dose He's Yangchao recipe treatment group and coenzyme Q10(Q10)treatment group(positive control).The POI model was induced by a single intraperitoneal injection of cyclophosphamide(90 mg/kg).The animals were sacrificed after 21 days.Primary granulose cells were obtained from POI mice and treated with He's Yangchao recipe,ERβ inhibitor PHTPP,and He's Yangchao recipe+PHTPP in vitro for 24 h,respectively.Ovarian histopathological changes were observed by hematoxylin-eosin(HE)staining,ATP levels were detected by luciferase assay,mtDNA copy numbers were detected by quantitative reverse transcriptase-polymerase chain reaction(qRT-PCR),mitochondrial structure changes were observed by transmission electron microscopy,protein and mRNA expression levels of estrogen receptor β(ERβ),peroxisome proliferator-activated receptor γ coactivator 1α(PGC1α),mitochondrial transcription factor A(TFAM),and superoxide dismutase 2(SOD2)were detected by Western blotting and qRT-PCR.Results:The ovarian tissue in model group exhibited few secondary and tertiary follicles,whereas the He's Yangchao recipe groups and Q10 group had abundant secondary and tertiary follicles.Compared with the blank control group,ATP and mtDNA levels in model group decreased(P＜0.01),mitochondrial crista disappeared or abnormal vacuolated structure increased;the protein and mRNA levels of ERβ,PGC1α,TFAM,and SOD2 decreased(all P＜0.01).ATP production increased in granulose cells of high-dose He's Yangchao recipe group and Q10 group;mtDNA copy numbers increased(P＜0.05 or P＜0.01);abnormal mitochondrial structure was reduced;the protein and mRNA expressions of ERβ,PGC1α,TFAM,and SOD2 increased(P＜0.05 or P＜0.01).Compared with the PHTPP intervention group,the proportion of normal mitochondrial structure in the granulose cells of He's Yangchao recipe+PHTPP group was higher;ATP content increased(P＜0.05 or P＜0.01);mtDNA copy numbers increased(P＜0.05 or P＜0.01);the protein and mRNA expression of ERβ,PGC1α,TFAM and SOD2 increased(P＜0.05 or P＜0.01).Conclusions:He's Yangchao recipe can regulate mitochondrial biogenesis through ERβ/PGC1α/TFAM pathway to improve ovarian function in POI mice.

Objective This study aimed to identify PAX9 variants in non-syndromic tooth agenesis families of Chi-na,as well as to analyze the genotype-phenotype of non-syndromic tooth agenesis caused by PAX9 variants,which can provide a basis for the genetic diagnosis of tooth agenesis.Methods We collected the data of 44 patients with non-syn-dromic oligodontia who underwent treatment at Stomatological Hospital of Hebei Medical University between 2018 and 2023.Whole-exome sequencing was performed on the peripheral blood of the proband and its core family members,and the variants were verified by Sanger sequencing.Pathogenicity analysis and function prediction of the variants were per-formed using bioinformatics tools.The correlation between the genotype of PAX9 variant and its corresponding pheno-type was examined by reviewing 55 publications retrieved from PubMed.The studies involved 232 tooth agenesis pa-tients with PAX9 variants.Results A novel PAX9 c.447delG(p.Pro150Argfs*62)and a reported PAX9 c.406C>T(p.Gln136*)were identified in two Chinese families.Through bioinformatics analysis and three-dimensional structural mod-eling,we postulated that the frameshift variant was pathogenic.The outcome was the premature cessation of PAX9 pro-tein,which caused severe structural and functional deficiencies.Summarizing the PAX9 genotype-phenotype relationship revealed that patients carrying the PAX9 variant commonly led to loss of the second molars.Conclusion We identified the novel PAX9 c.447delG(p.Pro150Argfs*62)in a Chinese family of non-syndromic oligodontia,expanding the known variant spectrum of PAX9.The most susceptible tooth position for PAX9 variants of tooth agenesis was the second mo-lars and the deciduous molars during the deciduous dentition.

Objective:To explore the relationship between knowledge of a friend's non-suicidal self-injury (NSSI) behavior and self injury and suicide behaviors of adolescents.Methods:From January 2020 to January 2021, totally 1 683 students from a middle school in Xiamen were randomly selected by cluster sampling.The suicide items of the self-injurious thoughts and behaviors interview(SITBT) were used to assess whether students were aware of their friends' self injurious history and their self injurious behaviors.The suicide items of the mini international neuropsychiatric interview for children and adolescents (MINI-KID) were used to assess students' suicide ideation and behavior.The data were statistically analyzed by SPSS 21.0 software.Logistic regression model was used to analyze the relationship between knowledge of a friend's NSSI and adolescents' own self-reported NSSI and suicidal behaviors.Results:A total of 1 683 junior and senior high school students completed the survey, including 412 (24.4%) who knew their friend's NSSI history and 1 271 (75.6%) who did not know their friend's NSSI history.There were statistically significant differences between the adolescents known and unknown friends' NSSI histories in terms of age, gender, whether they were left-behind children, mental disorders, their own NSSI, suicide attempts, and suicidal ideation (all P<0.05). Knowledge of a friend's NSSI behavior had positive predictive effect on adolescents' own NSSI behavior ( β=0.558, OR=2.01, 95% CI=1.58-3.88), suicidal ideation( β=0.238, OR=3.03, 95% CI=2.08-5.55), and suicide attempts ( β=0.233, OR=2.88, 95% CI=1.55-5.45) (all P<0.05). Conclusion:Knowledge of a friend's NSSI behavior may have an impact on adolescents' own self-injury and suicidal behavior.

Melatonin receptor 1B (MT2, encoded by the MTNR1B gene), a high-affinity receptor for melatonin, is associated with glucose homeostasis including glucose uptake and transport. The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus (GDM); however, the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood. This article aims to investigate the relationship between rs10830963 variants and GDM development, as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts. TaqMan-MGB (minor groove binder) probe quantitative real-time polymerase chain reaction (qPCR) assays were used for rs10930963 genotyping. MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence, western blot, and qPCR. The relationship between MT2 and glucose transporters (GLUTs) or peroxisome proliferator-activated receptor γ (PPARγ) was established by western blot, and glucose consumption of trophoblasts was measured by a glucose assay kit. The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women (P<0.05). The fasting, 1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers (P<0.05). Besides, the protein and messenger RNA (mRNA) expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women (P<0.05). Melatonin could stimulate glucose uptake and GLUT4 and PPARγ protein expression in trophoblasts, which could be attenuated by MT2 receptor knockdown. In conclusion, the rs10830963 variant was associated with an increased risk of GDM. The MT2 receptor is essential for melatonin to raise glucose uptake and transport, which may be mediated by PPARγ.
Female ; Humans ; Pregnancy ; Blood Glucose/metabolism* ; Diabetes, Gestational/metabolism* ; Glucose/metabolism* ; Melatonin/metabolism* ; Polymorphism, Genetic ; PPAR gamma ; Receptor, Melatonin, MT2/genetics*

OBJECTIVES: Adolescents are at high risk of non-suicidal self-injury (NSSI). Currently, there is no clinical assessment tool for adolescent NSSI behaviors measurement with global consistency. The Ottawa Self-injury Inventory (OSI) is considered as a relatively comprehensive assessment tool for NSSI, but the questionnaire is discussed with excessive content and timecostly, which may affect the reliability of the measurement results for adolescent.Thus, this study, based on OSI, aims to revise the assessment tool for adolescent with NSSI that is suitable for both clinically and scientifically, referring to the diagnostic criteria for NSSI in the 5th Diagnostic and Statistical Manual of Mental Disorder (DSM-5). METHODS: This study was led by the Second Xiangya Hospital of Central South University and collaborated with 6 mental health service institutions in China from August to December 2020. Adolescent aged from 12 to 24 years old who had self-injury behavior and met the DSM-5 diagnostic criteria for NSSI were continuously recruited in the psychiatric outpatient department or ward. After clinical diagnosis by an experienced attending psychiatrist or above, the general information and OSI were collected by questionnaires. SPSS 24.0 and AMOS structural equation model statistical softwares were used to conduct item analysis and exploratory factor analysis on the obtained data to complete the revision of the scale. Cronbach's alpha coefficient, split-half reliability, test-retest reliability, and content validity and structure validity were performed to analyze the reliability and validity and confirmatory factor analysis was carried out to test the structure validity for the revised scale. RESULTS: A total of 234 adolescent with NSSI were enrolled, including 33 (14.1%) males and 201 (85.9%) females with the mean age of (16.2±2.6) years old. The most common clinical diagnoses were depression disorder (57.4%), bipolar disorder (20.9%), adolescent mood disorder (17.1%), etc. Nine items (item 2, 7, 11, 13, 23, 24, 10, 17, 18) in the functional scale of OSI were deleted according to extreme grouping method, correlation analysis, and principal component analysis in exploratory factor analysis. The revised functional scale for NSSI consisted of 15 items. The reliability analysis showed that the Cronbach's alpha coefficients of NSSI thought and behavior frequency, addiction characteristics, and function scales were 0.799, 0.798, and 0.835, respectively, and the split-half coefficients were 0.714, 0.727, and 0.852, respectively. The test-retest coefficients of the latter 2 scales were 0.466 and 0.560, respectively. The correlation coefficient between sub-items and total scores in each part of the scale showed good content validity. The exploratory factor analysis showed that a component was extracted from the frequency of thoughts and behaviors of NSSI, one component was extracted from the addictive characteristics, and three components were extracted from the functional part. The three functional subscales were social influence, external emotion regulation, and internal emotion regulation. The factor load of each item was >0.400. CONCLUSIONS The revised Chinese version OSI targeted the adolescent patients with mental disorders has relatively ideal reliability and validity. The scale shows high stability, dependability, and a reasonable degree of fit. It is a suitable assessment tool for clinical and scientific research on adolescent with NSSI.
Adolescent ; Adult ; Child ; Factor Analysis, Statistical ; Female ; Humans ; Male ; Mental Disorders/diagnosis* ; Psychometrics/methods* ; Reproducibility of Results ; Self-Injurious Behavior/psychology* ; Surveys and Questionnaires ; Young Adult

Based on a research on judicial cases concerning the authenticity of electronic medical records in the past three years, the authors encountered judicial dilemmas in judicial practice. The challenges arise due to the special manifestations of electronic medical records, unclear and disputable criteria for the authenticity of electronic medical records, low application level of electronic medical records identification, and inconsistent responsibility attribution. In order to effectively apply the electronic medical record system, it is recommend to promote pre-litigation prevention by unifying the construction standards of the computerized patient record system, strengthening hospital electronic medical record management and entrusting third-party storage to ensure the evidential weight. In addition, it is necessary to establish standards for authenticity of medical records, improve the electronic medical record forensic identification system and clarify the attribution of the responsibility for untrue medical records, so as to improve the handling of such medical damage cases during litigation.

With the rapid development of " Internet+ healthcare" , medical data has gained an ever important role. How to determine the reasonable use boundary of medical data and leverage its supporting role, has grown an urgent problem to be solved. The authors analyzed the characteristics of medical data, and held that medical data is not equivalent to information, as it does not have the characteristics of legal objects in nature. In addition, it lacks originality. Therefore it is difficult to protect through the existing rights system. However, due to its property interest and personality, the authors tried to establish a new right for protection. In the construction of such medical data right, the authors claimed that patients should be the subject of the right, and medical institutions can appropriately restrict the freedom of patients′ through reasonable use rules and legal licensing system. In this way, we can not only promote medical data sharing and the development of social health, but also fully protect the legitimate rights and interests of patients.