OBJECTIVE: To analyze the clinical characteristics and genetic profile of patients with 46,XY Disorders of sex development (DSD) and a female phenotype in order to provide insights for the diagnosis and management of similar cases. METHODS: A retrospective analysis was conducted on 36 children with 46,XY DSD and a female phenotype who were treated at the Department of Endocrinology, Genetics and Metabolism of Henan Children's Hospital between March 1, 2016, and June 30, 2024. The evaluations included external genitalia scoring using the Prader scale and External Masculinization Score (EMS), imaging studies to assess gonadal development, and assessments of adrenal and gonadal function via adrenal hormone levels, sex hormone levels, and human chorionic gonadotropin (hCG) stimulation testing. Gender role behavior was assessed using gender role scales and sandplay therapy. Whole exome sequencing and Sanger sequencing were used to identify and validate genetic variants. A multidisciplinary team (MDT) comprehensively determined gender rearing based on molecular genetic diagnosis. This study was approved by the Medical Ethics Committee of Henan Children's Hospital (Ethics No.: 2024-K-105). RESULTS: The median age at initial consultation was 3 years and 1 month (range: 7 days to 16 years). Common symptoms included primary amenorrhea, clitoromegaly, and inguinal hernia. Fully feminized external genitalia were observed in 52.7% of the cases, and 80.5% had absence of the uterus. Internal gonads included absent gonads (5.6%), ovotestes (8.3%), streak gonads (5.6%), cryptorchidism (75.0%), and normally positioned testes (5.6%). At initial diagnosis, median luteinizing hormone (LH) was 1.305 IU/L, with elevated LH in 14 cases. Median follicle-stimulating hormone (FSH) was 4.87 IU/L, with elevated FSH in 17 cases. Median testosterone was 0.025 ng/mL. Median dihydrotestosterone (DHT) was 36.90 pg/mL. After hCG stimulation, median testosterone was 0.984 ng/mL and median DHT was 71.69 pg/mL. The testosterone/DHT ratio was elevated in one case (35.7). Testosterone levels remained below 1 ng/mL after hCG stimulation in 18 cases. Anti-Müllerian hormone (AMH) was decreased in 15 cases and increased in 3 cases. Inhibin B (InhB) was increased in 7 cases and decreased in 4 cases. Pathogenic variants were detected in 88.9% of the patients, involving AR (11 cases), CYP17A1 (4 cases), GATA4 (1 case), NR0B1 (1 case), NR5A1 (7 cases), SRD5A2 (1 case), WT1 (2 cases), STAR (4 cases), and LHCGR (1 case), totaling 34 variant sites. Among these, 9 variants were de novo, and 23 were inherited from parents. Sixteen variant sites were previously unreported. Gender assignment was male in 11 cases (30.6%) and female in 25 cases (69.4%). CONCLUSION Common symptoms in 46,XY DSD patients with a female phenotype include primary amenorrhea, clitoromegaly, and inguinal hernia. Elevated FSH, androgen deficiency, and decreased AMH and InhB may indicate testicular dysgenesis or impaired androgen synthesis. Adrenal insufficiency should raise suspicion for defects in steroid hormone synthesis pathway enzymes.
Humans ; Female ; Disorder of Sex Development, 46,XY/diagnosis* ; Child ; Male ; Phenotype ; Child, Preschool ; Retrospective Studies ; Adolescent ; Infant

Objective To explore the characteristics and influencing factors of family resilience among Chinese PLA Army personnel.Methods A total of 8 094 military personnel subjected with cluster sampling were surveyed with family resilience scale(FRS)and self-designed questionnaire for basic information on military families.Independent sample t test,one-way analysis of variance and step-up regression analysis were employed to analyze the family resilience.Results ① The results of demographic variable analysis showed that there were significant differences in family resilience among the personnel with different marital status,from one-child family or not,birth in rural/urban areas,personnel category,age and education level(P＜0.05).② Family factors analysis indicated that different family structure,different family relationships,family rearing styles,recent separation from family members,and frequency of contacting family members had certain effects on family resilience(P＜0.05).③ When family relationship,family rearing styles,frequency of contacting family members,birth place,recent separation from family,personnel category,from one-child family,and education level entered the regression equation,the resilience level of army personnel'families was increased by 8.197 for every 1 unit increase in family relationship,and the level of family resilience was increased by 4.688 for every 1 unit increase in family contact frequency(F=202.168,P＜0.05).Conclusion The overall level of family resilience of army personnel is good.The risk factors for family resilience are recent separation from their families for ≥1 year,officers,not from only-children family,and the protective factors are harmonious relationship with their families,democratic family rearing style,contacting with their families weekly,urban birth,and bachelor degree or above.

Objective:To investigate the correlation between triglyceride glucose index (TyG) and cerebral hemodynamic score values (CVHI) in population receiving physical examination.Methods:In this cross-sectional study, 12 785 people who had medical checkups and received physical examination at the Health Management Center of the First Affiliated Hospital of Xinjiang Medical University from June 2020 to May 2021 and met the criteria for natriuresis were selected as the study subjects. The general information, physical examination results and biochemical indexes were collected in these people. Using the visualization score box, the study subjects were divided into 4 groups according to TyG<8.379, 8.379-8.785, 8.785-9.236, and≥9.236: Q1 group (3 196 cases), Q2 group (3 196 cases), Q3 group (3 197 cases), and Q4 group (3 196 cases). The differences of the indices among the four groups were compared. The logistic regression analysis and Spearman rank correlation analysis were used to assess the correlation between TyG and CVHI in the population undergoing health checkups.Results:CVHI decreased gradually with the increase of TyG, and the abnormal rate of CVHI increased gradually with the increase of TyG ( H=451.007, χ2=188.571) (both P<0.001). The detection rates of individuals at high risk of CVHI in the Q1, Q2, Q3, and Q4 groups was 15.2%, 22.3%, 27.2%, and 35.3%, respectively. When TyG≥9.236, CVHI decreased in the population receiving physical examination ( OR=1.282, 95% CI: 1.028-1.598), and CVHI was negatively correlated with TyG ( rs=-0.200) (both P<0.05). Conclusion:There is a negative correlation between TyG and CVHI in the population receiving physical examination, and when TyG≥9.236, it suggests that cerebral hemodynamics may be abnormal, which warrants attention.

OBJECTIVE To explore the mechanism of modified Xianfang huoming decoction in the treatment of sepsis- induced liver injury from the perspective of gut microbiota and metabolites. METHODS Sixty SD rats were divided into blank group （normal saline）， model group （normal saline）， positive control drug group （Dexamethasone tablet， 5.0 mg/kg）， modified Xianfang huoming decoction high-dose， middle-dose and low-dose groups （6.0， 3.0， 1.5 g/kg， calculated by crude drug） according to equilibrium-partitioning approach of body mass， with 10 rats in each group. They were given relevant drug/normal saline 10 mL/ kg， once a day， for consecutive 14 days. After the last medication， except for blank group， other groups were given intraperitoneal injection of lipopolysaccharide 10 mg/kg to induce sepsis model. Twelve hours after modeling， serum levels of inflammatory indexes in rats [interleukin-1β （IL-1β）， IL-6， tumor necrosis factor-α （TNF-α）] and liver function indicators [total cholesterol （TC）， triglyceride （TG）， aspartate transaminase （AST）， alanine transaminase （ALT）] were detected. The changes of gut microbiota and liver metabolites in rats were analyzed by 16S rRNA technology and liver metabolomics. RESULTS Modified Xianfang huoming decoction could significantly improve the indexes of serum inflammatory indexes and liver function in rats with sepsis-induced liver injury （P＜0.05 or P＜0.01）； there was a significant callback effect on the relative abundance of 11 genera of bacteria （such as Akkermansia， Lactobacillus and Bilophila） among the 5 dominant phyla（P＜0.05 or P＜0.01）. Twelve metabolites related to liver injury caused by sepsis were identified， such as glycine cholic acid， phosphatidylcholine， taurine （P＜0.05 or P＜0.01）， mainly involving glycerol phospholipid metabolism， purine metabolism and primary bile acid metabolism. CONC LUSIONS Modified Xianfang huoming decoction can improve liver injury induced by sepsis by regulating gut microbiota and liver metabolites.

Objective:To evaluate the guidelines on discharged health education for solid organ transplant recipients at home and abroad, analyze the characteristics of each guideline, so as to provide reference for the development of health education for organ transplantation in China.Methods:This was a guideline quality evaluation study. The guidelines on health education for discharged recipients with solid organ transplantation were searched on the websites of clinical practice guidelines, the websites of transplantation professional associations, and Chinese and English databases at home and abroad through computers. The search time limit was from January 1, 2011 to January 1, 2022. The quality of guidelines that met the inclusion and exclusion criteria was evaluated using the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ) .Results:A total of 8 guidelines were included. The overall quality evaluation of the guideline was Grade A ( n=2) and Grade B ( n=6) . In terms of standardized scores in six areas of quality evaluation, the average values of scope and purpose, stakeholder involvement, rigour of development, clarity and presentation, applicability as well as editorial independence were 87.62% (70.37%-100.00%) , 75.46% (44.44%-97.22%) , 66.54% (43.75%-93.06%) , 90.16% (77.78%-96.30%) , 48.18% (20.83%-68.75%) and 74.13% (8.30%-97.22%) , respectively. The recommendations of the guidelines covered 9 aspects: team composition and support services, drug management, infection prevention, complication management, diet and nutrition, daily life and social reintegration, contraception and reproduction, psychological guidance and follow-up review. Conclusions:The development of guidelines for different types of solid organ transplantation varies. The overall quality of the guidelines needs to be improved and the content needs to be refined. In the future, we can learn from foreign high-quality guidelines to carry out localization practice, so as to build a health education related guideline for discharge of solid organ transplantation that is suitable for China's national conditions as soon as possible.

Objective:To study the therapeutic effect of liraglutide on rat models with non-alcoholic fatty liver disease (NAFLD) and its influence on the expression of fibroblast growth factor 21 (FGF21).Methods:Thirty five Sprague Dawley (SD) rats were randomly divided into normal control group (15 rats) and control group (20 rats). They were fed with normal diet and high fat diet respectively. The NAFLD rat model was established by feeding the model group for 12 weeks. After successful modeling, the model group was randomly divided into liraglutide group and model group. 600 μg/(kg·d) liraglutide and equal volume normal saline were injected intraperitoneally respectively. All rats were killed at the 16th week. Serum FGF21, alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting blood glucose (FBG), triglyceride (TG) and total cholesterol (TC) were measured; Hematoxylin-eosin (HE) staining was used to observe the pathological changes of rat liver tissue, and real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of FGF21 mRNA in rat liver tissue.Results:The liver index and serum ALT, AST, TC and TG contents in model group were significantly higher than those in normal control group (all P<0.05). The above indexes in liraglutide group were significantly lower than those in model group (all P<0.05). There was no significant difference in serum FBG level among the three groups ( P>0.05). HE staining showed that there were no abnormal pathological changes in liver of normal control group. Steatosis and inflammatory cell infiltration occurred in liver cells of model group. Compared with model group, liver steatosis and inflammatory cell infiltration in liraglutide group were significantly reduced. The level of FGF21 in serum and mRNA expression of FGF21 in liver tissue in model group were significantly higher than those in normal control group ( P<0.05). The levels of FGF21 in serum and FGF21 mRNA in liver tissue in liraglutide group were lower than those in model group ( P<0.05). Conclusions:Liraglutide can effectively delay the development of NAFLD in rats, and its mechanism may be related to the regulation of the expression of FGF21.

OBJECTIVE: To explore the genetic basis for a girl featuring bone and tooth mineralization disorder, premature deciduous teeth, rickets and short stature. METHODS: Genomic DNA was extracted and subjected to high-throughput whole exome sequencing. Suspected variants were confirmed by Sanger sequencing. Impact of potential variants was analyzed with bioinformatic software. RESULTS: The child was found to carry compound heterozygous missense variants of the ALPL gene, including c.1130C>T (p.A377V), a known pathogenic mutation inherited from her father, and c.1300G>A (p.V434M) inherited from her mother, which was unreported previously and predicted to be likely pathogenic based on standards and guidelines from the American College of Medical Genetics and Genomics (PM2+PM5+PP3+PP4). CONCLUSION The compound heterozygous variants of c.1130C>T (p.Ala377Val) and c.1300G>A (p.Val434Met) of the ALPL gene probably underlay the disease in this child. Above finding has enriched the spectrum of ALPL gene variants.
Alkaline Phosphatase ; Child ; Female ; Genomics ; High-Throughput Nucleotide Sequencing ; Humans ; Hypophosphatasia/genetics* ; Mutation ; Whole Exome Sequencing

Objective To investigate the endogenous carnosine,glutathione system and oxidative stress level in serum of patients with diabetic cardiomyopathy(DCM),and the potential relationships among them.Meth-ods The serum of 102 healthy people,96 patients with type 2 diabetes mellitus and 74 patients with diabetic car-diomyopathy in the third affiliated hospital of QiQihar Medical University were enrolled.Carnosine content was mea-sured by ELISA.T-GSH,GSH and GSSG were detected by using micro-enzyme labeling assay.GSH-Px,GST and GRAC were detected by using colorimetry. The content of NO was detected by nitrate reduction method. The con-tent of H2O2was detected by using molybdic acid coloring method. The activities of NOS and CAT was determined by colorimetry. Results Compared with the healthy control group,the average level of human serum carnosine, GSH content,GRAC,GSH/GSSG ratio,GST activity and T-SH content in the DM and DCM group were signifi-cantly reduced(P < 0.05,respectively). NO content,H2O2and iNOS activity were increased,but CAT activity was decreased in DCM group.Conclusion Decreases of levels of serum carnosine and glutathione(GSH)and the imbalance of redox state were observed in patients with diabetic cardiomyopathy,which may promote the occur-rence and development of the diabetic cardiomyopathy.

Objective To analyze the coincidence of the patients with capillary electrophoresis hemoglobin A 2 increase with defi-nitely diagnosed beta thalassaemia and to investigate its application value in the diagnosis of beta thalassaemia.Methods Two hundreds and sixty outpatients and inpatients with hemoglobin A 2 increase in our hospital from May 2014 to May 2015 were per-formed the genetic testing.Results Among 260 patients with hemoglobin A2 increase ,beta thalassemia gene mutations were detec-ted in 257 cases ,the coincidence rate reached 98.85% ,and the common 17 beta thalassemia gene mutations were not detected in the other 3 cases ,follow-up further detection of rare beta thalassaemia gene and beta globin gene sequencing was performed ,1 case of SEA-HPFH βdeletion type was found ,1 case was Taiwaneseβdeletion type and 1 case was Codon 89-93(-AGT GAG CTG CAC TG) heterozygous mutation ,it was verified that 3 cases of hemoglobin A2 increase without detecting 17 kinds of common beta thalassemia gene mutations were still beta chain mutation occurrence or big fragment deletion.At the same time ,among 257 speci-mens of beta thalassemia gene mutations ,42 cases were compound alpha thalassaemia ,accounting for 16.34% of beta thalassaemia. Conclusion Capillary electrophoresis hemoglobin A2 increase can provide a fast and accurate basis for beta thalassemia diagnosis , but which can not rule out the possibility of compoound alpha thalassaemia ,when the patient's hemoglobin A2 is increased ,alpha and beta thalassaemia genetic diagnosis should be simultaneously carried out.

Objective: To investigate the impact of gender and age on in-hospital major adverse cardiovascular and cerebrovascular events of patients with acute ST-segment elevation myocardial infarction (STEMI). Methods: This is a retrospective single-center study. A total of consecutive 1 102 patients with acute STEMI admitted to our hospital from January 2001 to December 2010 were recruited and clinical data were analyzed. The primary end point was in-hospital death due to any cause, and the secondary end point was in-hospital composite end point including death, re-infarction and stroke. Multivariate logistic regression analyses were performed to identify the risk factors of in hospital death and composite end point. Results: The study population included 283(25.7%(283/1 102)) female patients and female patients were older than male patients ((68.7±11.2)years vs. (59.2±12.5)years, P<0.001). Compared with male patients, less female patients received primary percutaneous coronary intervention (50.9%(144/283) vs. 70.9%(581/819), P<0.001), had higher rates of in hospital death(10.6%(30/283)vs. 6.0%(36/819), P<0.001) and composite endpoint(14.1%(40/283)vs. 7.0%(57/819), P<0.001). Among STEMI patients aged <60 years, no differences were found in in-hospital mortality (1.7%(1/58)vs. 1.4%(6/437)) and composite endpoint(3.6%(3/58)vs. 3.4%(15/437)) rates between female and male patients (both P>0.05). Among STEMI patients aged ≥60 years, female patients had higher in-hospital mortality (12.9%(29/225)vs. 7.9%(30/382), P<0.001), and there was no difference on composite endpoint between female and male patients (16.4%(37/225)vs. 11.0%(42/382), P=0.054). Multivariate logistic regression analysis showed that female gender was not the independent risk factor of in-hospital death(OR=1.029, 95%CI 0.564-1.877, P=0.926) and composite end point(OR=1.593, 95%CI 0.989-2.566, P=0.055), but age was the independent risk factor of in-hospital death(OR=1.065, 95%CI 1.037-1.094, P<0.001) and composite end point(OR=1.050, 95%CI 1.029-1.071, P<0.001)in STEMI patients. Multivariate logistic regression analysis also showed that female was not the independent risk factor of in-hospital death(OR=1.539, 95%CI 0.572-4.142, P=0.394) and composite end point(OR=1.563, 95%CI 0.689-3.546, P=0.285), but age was the independent risk factor of in-hospital death(OR=1.052, 95%CI 1.011-1.096, P=0.013) and composite end point(OR=1.042, 95%CI 1.008-1.077, P=0.016)in STEMI patients received primary percutaneous coronary intervention. Conclusion Female patients with STEMI have higher incidence of in-hospital major adverse cardiovascular and cerebrovascular events than male patients, and age is the independent risk factor of in-hospital major adverse cardiovascular and cerebrovascular events of STEMI patients.