Objective To investigate the intervention mechanism of Bushen Zhupai Decoction on polycystic ovary syndrome rats with insulin resistance based on IL-6/PI3K/AKT signaling pathway Methods A rat model of polycystic ovary syndrome with insulin resistance was established by feeding high-fat diet combined with oral administration of letrozole,and the blank group was fed with ordinary diet.The modeled rats were randomly divided into model group,metformin group and Bushen Zhupai Decoction low-,medium-and high-dosage groups.The corresponding intervention were given for 28 days.Fasting blood glucose(FBG)content was detected,and insulin resistance index(HOMA-IR)was calculated.ELISA was used to detect serum fasting insulin(FINS),testosterone(T),estradiol(E2),luteinizing hormone(LH)and follicle stimulating hormone(FSH)contents.HE staining was used to observe the morphology of ovarian tissue.Immunohistochemistry was used to detected the expressions of interleukin(IL)-6,p-PI3K,p-AKT and GLUT4 in ovarian tissue.Western blot was used to detect the protein expressions of IL-6,PI3K,p-PI3K,AKT,p-AKT and GLUT4 in ovarian tissue,while RT-PCR was used to detect the mRNA expressions of IL-6,PI3K,AKT and GLUT4.Results Compared with the blank group,the body mass,FBG,FINS and serum T and LH contents of the model group rats significantly increased(P<0.01),while the serum E2 and FSH contents significantly decreased(P<0.01);ovarian tissue showed polycystic changes,with reduced layers and loose arrangement of granulosa cells,the expression of IL-6 protein and mRNA in ovarian tissue significantly increased(P<0.01),the expressions of p-PI3K,p-AKT and GLUT4 proteins significantly decreased(P<0.01),and the expressions of PI3K,AKT and GLUT4 mRNA significantly decreased(P<0.01).Compared with the model group,the body mass of rats in each administration group decreased,and the contents of FBG,FINS and serum T and LH decreased(P<0.01,P<0.05),while the contents of E2 and FSH increased;polycystic changes in ovarian tissue were reduced,mature follicles increased,and granulosa cells were tightly arranged,the expression of IL-6 protein and mRNA in ovarian tissue decreased,the expressions of p-PI3K,p-AKT,GLUT4 protein and PI3K,AKT,GLUT4 mRNA increased.Bushen Zhupai Decoction high-dosage group showed statistical significance(P<0.01).Conclusion Bushen Zhupai Decoction can improve reproductive and metabolic disorders in polycystic ovary syndrome with insulin resistance rats,and its mechanism may be related to inhibiting IL-6 expression,activating the PI3K/AKT signaling pathway,and alleviating insulin resistance.

Objective:To analyze the clinical characteristics and gene mutations of 4 patients with the male phenotype of 17α-hydroxylase /17, 20-lyase deficiency(17-OHD), in order to improve the recognition and appropriate management of atypical cases.Methods:A retrospective analysis was performed on the clinical features, biochemical findings, and gene mutations of 4 patients with the male phenotype of 17-OHD treated in our hospital between 2018 and 2023.Results:The social gender of all 4 patients with 17-OHD was male. None of the 4 patients had hypertension or hypokalemia, but all had micropenis and gynecomastia. Two patients had adrenal hyperplasia, while adrenal morphology was normal in the other two. One patient had decreased bone mass. There were typical changes in the steroid synthesis-related hormone spectrum: progesterone was significantly elevated in all 4 patients, 17-hydroxyprogesterone was not markedly abnormal, cortisol, dehydroepiandrosterone sulfate(DHEAS) and estradiol levels were low, and testosterone levels were also low.Conclusion:17-OHD is a rare type of congenital adrenal hyperplasia, with the male phenotype being even rarer. Early symptoms are often atypical, resulting in high rates of misdiagnosis and missed diagnosis. Patients without hypertension and hypokalemia are particularly prone to diagnostic confusion. Male patients with unexplained progesterone elevation, poor secondary sexual development, and gynecomastia should undergo timely steroid hormone profiling and genetic testing to avoid misdiagnosis and missed diagnosis.

Objective To explore the mechanism of Bushen Zhupai Decoction in treating ovarian fibrosis in polycystic ovary syndrome(PCOS)model rats based on IL-17/TRAF6/NF-κB signaling pathway.Methods Totally 60 SPF grade female SD rats were randomly divided into blank group,model group,Yousiyue group and TCM low-,medium-and high-dosage groups,with 10 rats in each group.The PCOS model was replicated by gavage of 1 mg/kg letrozole for 21 days.The Yousiyue group was given a 10 mg/kg solution of drospirenone ethinylestradiol tablets by gavage,TCM low-,medium-and high-dosage groups were given 8.82,17.64 and 35.28 g/kg of Bushen Zhupai Decoction by gavage,once a day for 28 consecutive days.HE and Masson staining were used to observe the morphology of ovarian tissue and ovarian fibrosis,the contents of serum IL-17,IL-18 and IL-1β were detected by ELISA,the mRNA expression of IL-17,TRAF6,NF-κB p65 and TGF-β1 in ovarian tissue were determined by RT-qPCR,the protein expression of TRAF6,NF-κB p65,TGF-β1,α-SMA,E-cadherin and the positive expression of IL-17RA,TRAF6,NF-κB p65,TGF-β1 and α-SMA in ovarian tissue were detected by Western blot and immunohistochemical staining respectively.Results Compared with the blank group,the body mass,ovarian mass and ovarian index significantly increased of rats in model group,with follicular cystic dilation,thinning of granulosa cell layer,and significant increase in fibrosis positive range(P<0.01),the serum contents of IL-17,IL-18 and IL-1β significantly increased(P<0.01),the expressions of IL-17,TRAF6,NF-κB p65,TGF-β1 mRNA and IL-17RA,TRAF6,NF-κB p65,TGF-β1 and α-SMA proteins significantly increased(P<0.01,P<0.05),the expression of E-cadherin protein significantly decreased(P<0.01).Compared with the model group,the ovarian index of rats in Yousiyue group and TCM medium-and high-dosage groups significantly decreased(P<0.01,P<0.05),the rats in TCM high-dosage group showed dominant follicles,increased thickness of granulosa cell layer,and significantly reduced fibrosis positive range(P<0.01),the serum contents of IL-17,IL-18 and IL-1β significantly decreased in Yousiyue group and TCM low-,medium-and high-dosage groups(P<0.01),the mRNA expressions of IL-17,TRAF6,NF-κB p65,TGF-β1,and the protein expressions of IL-17RA,TRAF6,NF-κB p65,TGF-β1 and α-SMA in ovarian tissue significantly decreaed in TCM high-dosage group(P<0.01,P<0.05),the expression of E-cadherin protein significantly increased(P<0.01).Conclusion Bushen Zhupai Decoction can decrease the body mass,improve the ovarian index,decrease the expressions of inflammatory factors and improve the status of ovarian fibrosis in PCOS rats.The mechanism may be related to the regulation of IL-17/TRAF6/NF-κB signaling pathway.

Objective To explore the mechanism of Bushen Zhupai Decoction in treating ovarian fibrosis in polycystic ovary syndrome(PCOS)model rats based on IL-17/TRAF6/NF-κB signaling pathway.Methods Totally 60 SPF grade female SD rats were randomly divided into blank group,model group,Yousiyue group and TCM low-,medium-and high-dosage groups,with 10 rats in each group.The PCOS model was replicated by gavage of 1 mg/kg letrozole for 21 days.The Yousiyue group was given a 10 mg/kg solution of drospirenone ethinylestradiol tablets by gavage,TCM low-,medium-and high-dosage groups were given 8.82,17.64 and 35.28 g/kg of Bushen Zhupai Decoction by gavage,once a day for 28 consecutive days.HE and Masson staining were used to observe the morphology of ovarian tissue and ovarian fibrosis,the contents of serum IL-17,IL-18 and IL-1β were detected by ELISA,the mRNA expression of IL-17,TRAF6,NF-κB p65 and TGF-β1 in ovarian tissue were determined by RT-qPCR,the protein expression of TRAF6,NF-κB p65,TGF-β1,α-SMA,E-cadherin and the positive expression of IL-17RA,TRAF6,NF-κB p65,TGF-β1 and α-SMA in ovarian tissue were detected by Western blot and immunohistochemical staining respectively.Results Compared with the blank group,the body mass,ovarian mass and ovarian index significantly increased of rats in model group,with follicular cystic dilation,thinning of granulosa cell layer,and significant increase in fibrosis positive range(P<0.01),the serum contents of IL-17,IL-18 and IL-1β significantly increased(P<0.01),the expressions of IL-17,TRAF6,NF-κB p65,TGF-β1 mRNA and IL-17RA,TRAF6,NF-κB p65,TGF-β1 and α-SMA proteins significantly increased(P<0.01,P<0.05),the expression of E-cadherin protein significantly decreased(P<0.01).Compared with the model group,the ovarian index of rats in Yousiyue group and TCM medium-and high-dosage groups significantly decreased(P<0.01,P<0.05),the rats in TCM high-dosage group showed dominant follicles,increased thickness of granulosa cell layer,and significantly reduced fibrosis positive range(P<0.01),the serum contents of IL-17,IL-18 and IL-1β significantly decreased in Yousiyue group and TCM low-,medium-and high-dosage groups(P<0.01),the mRNA expressions of IL-17,TRAF6,NF-κB p65,TGF-β1,and the protein expressions of IL-17RA,TRAF6,NF-κB p65,TGF-β1 and α-SMA in ovarian tissue significantly decreaed in TCM high-dosage group(P<0.01,P<0.05),the expression of E-cadherin protein significantly increased(P<0.01).Conclusion Bushen Zhupai Decoction can decrease the body mass,improve the ovarian index,decrease the expressions of inflammatory factors and improve the status of ovarian fibrosis in PCOS rats.The mechanism may be related to the regulation of IL-17/TRAF6/NF-κB signaling pathway.

Objective To investigate the intervention mechanism of Bushen Zhupai Decoction on polycystic ovary syndrome rats with insulin resistance based on IL-6/PI3K/AKT signaling pathway Methods A rat model of polycystic ovary syndrome with insulin resistance was established by feeding high-fat diet combined with oral administration of letrozole,and the blank group was fed with ordinary diet.The modeled rats were randomly divided into model group,metformin group and Bushen Zhupai Decoction low-,medium-and high-dosage groups.The corresponding intervention were given for 28 days.Fasting blood glucose(FBG)content was detected,and insulin resistance index(HOMA-IR)was calculated.ELISA was used to detect serum fasting insulin(FINS),testosterone(T),estradiol(E2),luteinizing hormone(LH)and follicle stimulating hormone(FSH)contents.HE staining was used to observe the morphology of ovarian tissue.Immunohistochemistry was used to detected the expressions of interleukin(IL)-6,p-PI3K,p-AKT and GLUT4 in ovarian tissue.Western blot was used to detect the protein expressions of IL-6,PI3K,p-PI3K,AKT,p-AKT and GLUT4 in ovarian tissue,while RT-PCR was used to detect the mRNA expressions of IL-6,PI3K,AKT and GLUT4.Results Compared with the blank group,the body mass,FBG,FINS and serum T and LH contents of the model group rats significantly increased(P<0.01),while the serum E2 and FSH contents significantly decreased(P<0.01);ovarian tissue showed polycystic changes,with reduced layers and loose arrangement of granulosa cells,the expression of IL-6 protein and mRNA in ovarian tissue significantly increased(P<0.01),the expressions of p-PI3K,p-AKT and GLUT4 proteins significantly decreased(P<0.01),and the expressions of PI3K,AKT and GLUT4 mRNA significantly decreased(P<0.01).Compared with the model group,the body mass of rats in each administration group decreased,and the contents of FBG,FINS and serum T and LH decreased(P<0.01,P<0.05),while the contents of E2 and FSH increased;polycystic changes in ovarian tissue were reduced,mature follicles increased,and granulosa cells were tightly arranged,the expression of IL-6 protein and mRNA in ovarian tissue decreased,the expressions of p-PI3K,p-AKT,GLUT4 protein and PI3K,AKT,GLUT4 mRNA increased.Bushen Zhupai Decoction high-dosage group showed statistical significance(P<0.01).Conclusion Bushen Zhupai Decoction can improve reproductive and metabolic disorders in polycystic ovary syndrome with insulin resistance rats,and its mechanism may be related to inhibiting IL-6 expression,activating the PI3K/AKT signaling pathway,and alleviating insulin resistance.

Objective:To analyze the clinical characteristics and gene mutations of 4 patients with the male phenotype of 17α-hydroxylase /17, 20-lyase deficiency(17-OHD), in order to improve the recognition and appropriate management of atypical cases.Methods:A retrospective analysis was performed on the clinical features, biochemical findings, and gene mutations of 4 patients with the male phenotype of 17-OHD treated in our hospital between 2018 and 2023.Results:The social gender of all 4 patients with 17-OHD was male. None of the 4 patients had hypertension or hypokalemia, but all had micropenis and gynecomastia. Two patients had adrenal hyperplasia, while adrenal morphology was normal in the other two. One patient had decreased bone mass. There were typical changes in the steroid synthesis-related hormone spectrum: progesterone was significantly elevated in all 4 patients, 17-hydroxyprogesterone was not markedly abnormal, cortisol, dehydroepiandrosterone sulfate(DHEAS) and estradiol levels were low, and testosterone levels were also low.Conclusion:17-OHD is a rare type of congenital adrenal hyperplasia, with the male phenotype being even rarer. Early symptoms are often atypical, resulting in high rates of misdiagnosis and missed diagnosis. Patients without hypertension and hypokalemia are particularly prone to diagnostic confusion. Male patients with unexplained progesterone elevation, poor secondary sexual development, and gynecomastia should undergo timely steroid hormone profiling and genetic testing to avoid misdiagnosis and missed diagnosis.

Objective:To investigate the effect of growth hormone replacement therapy(GHRT) on glucose and lipid metabolism in patients with hypopituitarism.Methods:Clinical data of patients with hypopituitarism who received GHRT in Department of Endocrine and Metabolic Diseases, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from December 2016 to February 2020 were retrospectively analyzed. The patients were divided into normal glucose regulation(NGR) group and impaired glucose regulation(IGR) group according to their glucose metabolism status before GHRT. The changes of the characteristics of glucose metabolism before and after GHRT were analyzed.Results:A total of 30 patients aged(23.0±5.2) years were included, 23 patients in NGR group and 7 patients in IGR group. After 12 months of GHRT, there were no significant changes in fasting plasma glucose(FPG), 2-hour postprandial plasma glucose(2hPG), and insulin sensitivity index(ISI) in both groups(all P>0.05), while homeostasis model assessment insulin resistance(HOMA-IR) in IGR group was significantly decreased compared with that before GHRT( P<0.05). None of the patients in NGR group progressed to IGR or diabetes mellitus, and none of the 7 patients in the IGR group progressed to diabetes mellitus, while 4 of them recovered from impaired glucose tolerance(IGT) to NGR. Triglyceride, total cholesterol, and low density lipoprotein-cholesterol levels were all significantly decreased in two groups(all P<0.05). Multivariate linear regression analysis showed that the increase of body mass index was an independent risk factor for the increase of FPG and 2hPG( P<0.05). Conclusion:12-month GHRT significantly improved their blood lipid profiles in patients with hypopituitarism without adversely affecting glucose homeostasis.

Autophagy is a critical cellular homeostatic mechanism, and its dysfunction is linked to invasive breast carcinoma (BRCA). Recently, several omics methods have been applied to explore autophagic regulators in BRCA; however, more reliable and robust approaches for identifying crucial regulators and druggable targets remain to be discovered. Thus, we report here the results of multi-omics approaches to identify potential autophagic regulators in BRCA, including gene expression (EXP), DNA methylation (MET) and copy number alterations (CNAs) from The Cancer Genome Atlas (TCGA). Newly identified candidate genes, such as

Objective To analyze clinical characteristics and gene mutation of two patients diagnosed with P450 oxidoreductase deficiency(PORD). Methods Clinical data of 2 patients with PORD was collected from Ruijin hospital. POR gene mutation was analyzed by PCR-Sanger sequencing. A retrospective analysis of literatures concerning PORD was performed. Results Patient 1, female, 16 years old, with 46,XX karyotype, presented with anorectal anomalies, clitoral hypertrophy at birth and irregular menstruation; Patient 2, female, 32 years old, with 46,XX karyotype, showed irregular menstruation and infertility, both without obvious skeletal deformity. Genetic test of POR gene mutation revealed that patient 1 carried a homozygous missense mutation (R457H) and patient 2 carried a heterozygous mutation (R223X/ Y607C). The two mutations (R223X and Y607C) are reported for the first time in China. Conclusion P450 oxidoreductase deficiency which caused by mutations in POR gene has a variety of clinical manifestations, including abnormal steroid hormone synthesis with or without Antley-Bixler syndrome. The affirmative diagnosis should rely on steroid hormone measurement and POR gene analysis.

Objective To explore more suitable calculation method of the insulin dosage in insulin hypoglycemia-growth hormone stimulation test(insulin tolerance test, ITT). Methods Fifty-six subjects suspected of growth hormone deficiency were divided into primary and secondary onset groups. All the patients took oral glucose tolerance test and ITT. Homeostasis model of assessment for insulin resistance index ( HOMA-IR) and insulin sensitivity index ( ISI), area under insulin curve ( AUCINS ) and the area under glucose curve ( AUCPG ) were calculated. The insulin dosages during ITT between two groups were compared and the main factors influencing the insulin dosage were analyzed. Results There was no difference in the insulin dosage during ITT between primary and secondary groups. The actual dosage of insulin in this cohort study revealed a significant difference from the initial insulin dosage recommended by the guideline. Multiple linear regression analysis found that AUCINS and body mass index were the independent factors affecting the insulin dosage. Then the optimized coefficient of ITT ( γ) were found. Conclusion The insulin dosage used in our study was inconsistent with the guidelines-recommended ones. In order to make ITT more efficient and safer, a more optimized calculation method to improve the successful rate of insulin-induced hypoglycemia in ITT is proposed.