Objective To investigate the effect of oxymatrine on the brain damage of rats with acute carbon monoxide(CO)poisoning through the sirtuin 1(SIRT1)/forkhead box protein O1(FOXO1)signaling pathway.Methods SD rats were used to establish an acute CO poisoning rat model,after intervention with low,medium,and high doses of oxymatrine and edaravone,the cognitive function of the rats was tested using shuttle box experiments to screen for the optimal dosage of oxymatrine.Construct a rat model of acute CO poisoning againand randomly divide it into five groups:control group,model group,oxymatrine group,edaravone group,EX527(SIRT1 inhibitor)group,and oxymatrine+EX527 group,the model group and drug intervention groupinhaled CO gas to construct acute CO poisoning rat model.After drug intervention,the shuttle box experiment was used to detect the cognitive function in rats,the step-through latency(STL)and the total time spent in the dark chamber(TDC)of each group were compared;fluorescent probe was performed to measure the mitochondrial membrane potential of rat brain tissue;TUNEL staining was performed to detect the apoptosis rate of hippocampal neurons in the rat brain;the kit was performed to determine the levels of serum inflammatory factors and the oxidative stress factor;immunoblotting and immunoprecipitation experimentswas performed to determine the expression of SIRT1/FOXO1 pathway protein.Results Compared with the control group,the STL,brain mitochondrial membrane potential,serum SOD level,and brain tissue SIRT1 protein expression in the model group were significantly reduced(P＜0.05),and the TDC,neuron apoptosis rate,serum ROS,PGE2,TNF-α,IL-18 and MDA levels,and brain tissue acely-FOXO1/FOXO1 were significantly increased(P＜0.05).Compared with the model group and the oxymatrine+EX527 group,the STL,brain mitochondrial membrane potential,serum SOD level,and brain tissue SIRT1 protein expression were all increased in the oxymatrine group(P＜0.05),and the TDC,neuron apoptosis rate,serum ROS,PGE2,TNF-α,IL-18 and MDA levels,and brain tissue acely-FOXO1/FOXO1 were all decreased(P＜0.05);the trend of changes in various indicators in the EX527 group is opposite to that of the oxymatrine group(P＜0.05).There was no significant change in the levels of various indicators between the edaravone group and the high-dose oxymatrine group(P＞0.05).Conclusion Oxymatrine can activate SIRT1/FOXO1 signal to reduce inflammation and oxidative stress in rats,inhibit hippocampal neuronal apoptosis,repair brain mitochondrial function,enhance cognitive ability of rats,and improve brain damage of acute CO poisoning rats.

Objective To investigate the effect of oxymatrine on the brain damage of rats with acute carbon monoxide(CO)poisoning through the sirtuin 1(SIRT1)/forkhead box protein O1(FOXO1)signaling pathway.Methods SD rats were used to establish an acute CO poisoning rat model,after intervention with low,medium,and high doses of oxymatrine and edaravone,the cognitive function of the rats was tested using shuttle box experiments to screen for the optimal dosage of oxymatrine.Construct a rat model of acute CO poisoning againand randomly divide it into five groups:control group,model group,oxymatrine group,edaravone group,EX527(SIRT1 inhibitor)group,and oxymatrine+EX527 group,the model group and drug intervention groupinhaled CO gas to construct acute CO poisoning rat model.After drug intervention,the shuttle box experiment was used to detect the cognitive function in rats,the step-through latency(STL)and the total time spent in the dark chamber(TDC)of each group were compared;fluorescent probe was performed to measure the mitochondrial membrane potential of rat brain tissue;TUNEL staining was performed to detect the apoptosis rate of hippocampal neurons in the rat brain;the kit was performed to determine the levels of serum inflammatory factors and the oxidative stress factor;immunoblotting and immunoprecipitation experimentswas performed to determine the expression of SIRT1/FOXO1 pathway protein.Results Compared with the control group,the STL,brain mitochondrial membrane potential,serum SOD level,and brain tissue SIRT1 protein expression in the model group were significantly reduced(P＜0.05),and the TDC,neuron apoptosis rate,serum ROS,PGE2,TNF-α,IL-18 and MDA levels,and brain tissue acely-FOXO1/FOXO1 were significantly increased(P＜0.05).Compared with the model group and the oxymatrine+EX527 group,the STL,brain mitochondrial membrane potential,serum SOD level,and brain tissue SIRT1 protein expression were all increased in the oxymatrine group(P＜0.05),and the TDC,neuron apoptosis rate,serum ROS,PGE2,TNF-α,IL-18 and MDA levels,and brain tissue acely-FOXO1/FOXO1 were all decreased(P＜0.05);the trend of changes in various indicators in the EX527 group is opposite to that of the oxymatrine group(P＜0.05).There was no significant change in the levels of various indicators between the edaravone group and the high-dose oxymatrine group(P＞0.05).Conclusion Oxymatrine can activate SIRT1/FOXO1 signal to reduce inflammation and oxidative stress in rats,inhibit hippocampal neuronal apoptosis,repair brain mitochondrial function,enhance cognitive ability of rats,and improve brain damage of acute CO poisoning rats.

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 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.

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.

Objective:To analyze clinical and genetic characteristics of congenital hypogonadotropic hypogonadism(CHH) in children.Methods:Clinical data of 0-18 year old CHH patients diagnosed in the Department of Endocrinology, Genetics and Metabolism of Children′s Hospital Affiliated to Zhengzhou University from January 1, 2016 to December 31, 2023 were retrospectively analyzed, including their hormone levels and genetic test results.Results:A total of 95 patients with CHH were included. Among them, 25 were diagnosed before the age of 3, 37 between the ages of 3-14, and 33 were over 14 years old at the time of first diagnosis. The primary manifestations were micropenis(95 cases, 100%) and cryptorchidism(46 cases, 48.5%). The incidence of cryptorchidism was the lowest in the group over 14 years of age. Hormonal analysis revealed that the peak levels of LH following statin B and GnRH stimulation, the peak levels of FSH after GnRH stimulation, and testosterone levels following hCG stimulation were the highest in the infant group. Genetic analysis identified 20 CHH-related genes in 61 out of 77 cases.Double-gene mutation accounted for 7.8%(6/77) and triple-gene mutation accounted for 3.9%(3/77). The most common mutations were FGFR1(18/77, 23.4%), CHD7(12/77, 15.6%), PROKR2(11/77, 14.3%) and ANOS1(6/77, 7.8%). The incidence of cryptorchidism in these four genotypes was 50%, 75%, 45.5% and 83.3%, respectively. The incidence of testicular dysfunction was 22.2%, 16.7%, 27.3%, and 16.7%, respectively, with no statistical significance.Conclusion:The primary manifestation of CHH is micropenis and cryptorchidism. In children with CHH, the incidence of testicular Leydig cell and Sertoli cell dysfunction increased with age in CHH children. FGFR1, CHD7, PROKR2 and ANOS1 were common variants of CHH.

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 investigate the expression of carcinoembryonic antigen-related cell adhesion molecule 19 (CEACAM19) in colorectal cancer tissues, and evaluate the clinical pathological characters and prognostic significance. Methods: Ninety-eight patients with colorectal cancer in Beijing Huairou Hospital from July 2015 to July 2018 were selected. The expression level of CEACAM19 protein in primary colorectal cancer and corresponding non-tumor tissues (>2 cm) was detected by immunohistochemistry. The correlation between clinical pathological characters and CEACAM19 expression level was analyzed. The prognostic influencing factors were analyze by univariate and multivariate Cox regression methods. Survival curve was drawn by Kaplan-Meier method. Results: The high expression rate of CEACAM19 in colorectal cancer tissues was significantly higher than that in adjacent non-tumor tissues: 69.4% (68/98) vs. 16.3% (16/98), and there was statistical difference (χ² = 45.060; P<0.01). Expression of CEACAM19 in colorectal cancer tissues was significantly associated with TNM stage (P<0.05), and was not associated with age, gender, tumor diameter, histological differentiation, tumor location, lymph node stage and invasion depth (P>0.05). Univariate Cox regression analysis result showed that lymph node stage, TNM stage and CEACAM19 expression were influencing factors of overall survival in patients with colorectal cancer (P<0.05 or <0.01), and the TNM stage and CEACAM19 expression were influencing factors of disease-free survival in patients with colorectal cancer (P<0.01). Multivariate Cox regression analysis result showed that TNM stage increased and CEACAM19 high expression were independent risk factors of overall survival (HR = 2.628 and 0.199, 95% CI 1.147 to 6.021 and 0.045 to 0.868, P = 0.022 and 0.032) and disease-free survival (HR = 2.009 and 0.303, 95% CI 0.965 to 4.185 and 0.101 to 0.911, P = 0.048 and 0.034) in patients with colorectal cancer. Survival curve analysis result showed that the median overall survival and disease-free survival in CEACAM19 low expression patients were significantly longer than CEACAM19 high expression patients (47.9 months vs. 27.8 months and 43.2 months vs. 26.3 months, P<0.01); the median overall survival and disease-free survival in TNM Ⅰ to Ⅱ stage were significantly longer than TNM Ⅲ stage patients (43.9 months vs. 24.2 months and 39.3 months vs. 23.7 months, P<0.01). Conclusions The CEACAM19 in colorectal cancer tissues is high expression, and the CEACAM19 expression level can be used as biomarker for prediction the prognosis of colorectal cancer.

Objective To explore the clinical value of Z score in assessing coronary artery lesions (CAL) of children with Kawasaki disease. Methods The clinical records of 102 children with Kawasaki disease from January 2012 to December 2016 in Gansu Provincial Hospital were retrospectively analyzed. The internal diameter of left main coronary artery (LMCA) and right coronary artery ( RCA) was measured by echocardiography (ECHO),and the incidence of CAL was preliminarily judged. The Z scores of LMCA and RCA were calculated on the basis of the coronary artery diameter,the age of the children and the body surface area,and the incidence of CAL was judged again. Results A total of 22 cases(21. 6%) of CAL were found in 102 cases by ECHO examination,of which 18 cases(17. 6%) of LMCA lesions,and 22 cases(21. 6%) of RCA lesions. A total of 33 cases(32. 4%) of CAL were found by calculating the Z score of coronary artery, of which 29 cases(28. 4%) of LMCA lesions and 33 cases(32. 4%) of RCA lesions. There was significant difference between two methods for determining LMCA lesions (χ2=3. 35,P＜0. 05),and there was no sig-nificant difference between two methods for determining RCA lesions (χ2=3. 01,P＞0. 05). Z score of coro-nary artery was more accurate to detect the CAL in Kawasaki disease,especially LMCA lesions. A large coro-nary artery aneurysm was found in the patients with the largest Z score by selective coronary angiography. Conclusion The Z score can be more conductive to assess the CAL in children with Kawasaki disease,and the higher the Z score,the more serious the CAL is.

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.