麒麟丸联合炔雌醇环丙孕酮对多囊卵巢综合征致不孕症患者子宫内膜容受性、血清性激素和氧化应激水平的影响

摘要 目的：探讨麒麟丸联合炔雌醇环丙孕酮对多囊卵巢综合征（PCOS）致不孕症患者子宫内膜容受性、血清性激素和氧化应激水平的影响。方法：选取我院于2018年1月~2020年1月期间收治的PCOS致不孕症患者460例,符合要求的患者按照随机数字表法分为对照组和研究组,各为230例。对照组患者予以炔雌醇环丙孕酮治疗,研究组予以麒麟丸联合炔雌醇环丙孕酮治疗,对比两组疗效、子宫内膜容受性、性激素、氧化应激、排卵率、妊娠率和不良反应。结果：研究组的临床总有效率较对照组更高（P<0.05）。研究组治疗后子宫动脉搏动指数（PI）、子宫动脉血流阻力指数（RI）低于对照组,子宫内膜厚度大于对照组（P<0.05）。研究组治疗后促卵泡激素（FSH）和黄体生成素（LH）低于对照组,雌二醇（E2）高于对照组（P<0.05）。研究组治疗后丙二醛（MDA）、活性氧物质（ROS）低于对照组,过氧化物歧化酶（SOD）高于对照组（P<0.05）。随访6个月后,研究组的妊娠率、排卵率明显高于对照组（P<0.05）。两组不良反应发生率组间对比无差异（P>0.05）。结论：麒麟丸联合炔雌醇环丙孕酮治疗PCOS致不孕症患者,可以有效改善患者子宫内膜容受性、血清性激素和氧化应激状态,提高妊娠率、排卵率,安全有效。     

补脾滋肾汤联合针灸治疗多囊卵巢综合征不孕症的临床疗效观察

摘要 目的：观察补脾滋肾汤联合针灸治疗多囊卵巢综合征（PCOS）不孕症的临床疗效。方法：选择2018年9月~2020年9月就诊的120例PCOS不孕症患者,随机分为观察组和对照组各60例。均给予口服枸橼酸氯米芬基础治疗,观察组在基础治疗上增加补脾滋肾汤联合针灸治疗,28 d为一个治疗周期,对比两组患者3个疗程后总有效率、中医证候量表评分、BMI（体质量指数）、月经情况、排卵情况、妊娠情况、血清性激素指标[T（睾酮）、LH（促黄体生成激素）、FSH（促卵泡生成激素）]、B超测定子宫内膜容受性指标[子宫内膜厚度、PI（子宫内膜螺旋动脉搏动指数）与RI（阻力指数）]。结果：治疗3个疗程后观察组的临床总有效率为90%（54/60）,高于对照组的83%（50/60）（P<0.05）。经过3个疗程治疗后,两组PCOS不孕症患者中医症候量表评分改善,月经情况改善,两组排卵率、妊娠率提高,且观察组高于对照组（P<0.05）。治疗3个疗程后,两组BMI、RI、PI、LH、T均下降,且观察组低于对照组（P<0.05）;两组子宫内膜厚度、FSH均增高,且观察组高于对照组（P<0.05）。结论：补脾滋肾汤联合针灸治疗多囊卵巢综合征不孕患者通过中药滋补脾肾、针灸治疗后,有效缓解了临床症状,性激素水平得到调节、体重减轻,提高调经促排卵助孕率,疗效确切。     

加味补中益气汤治疗肥胖型多囊卵巢综合征患者的疗效及对子宫内膜容受性和糖脂代谢的影响

摘要 目的：探讨加味补中益气汤治疗肥胖型多囊卵巢综合征（PCOS）患者的疗效及对子宫内膜容受性和糖脂代谢的影响。方法：选择2018年3月~2020年5月期间我院收治的肥胖型PCOS患者280例，采用抽签法分为观察组140例和对照组140例。对照组给予二甲双胍片治疗，观察组给予加味补中益气汤治疗，对比两组疗效、体质量指数（BMI）、腰臀比、性激素指标[雌二醇（E2），促黄体生成激素（LH）、卵泡刺激素（FSH）]、子宫内膜容受性指标[子宫内膜厚度、子宫内膜螺旋动脉搏动指数（PI）与阻力指数（RI）]、糖脂代谢指标[总胆固醇(TC)、低密度脂蛋白 (LDL-C)、甘油三酯(TG)、高密度脂蛋白 (HDL-C)、空腹血糖（FPG）]。结果：观察组的临床总有效率为92.14%（129/140），高于对照组的80.71%（113/140）（P<0.05）。治疗3个月经周期后，两组BMI、腰臀比、PI、RI、LH、FSH、TC、LDL-C、TG、FPG均下降，且观察组低于对照组（P<0.05）。治疗3个月经周期后，两组子宫内膜厚度、HDL-C、E2升高，且观察组高于对照组（P<0.05）。结论：加味补中益气汤治疗肥胖型PCOS患者，可降低患者体质量，调节性激素、子宫内膜容受性和糖脂代谢水平，具有较好的疗效。     

苍附导痰汤联合通元针法对脾虚痰湿型多囊卵巢综合征患者脂代谢、性激素和子宫内膜容受性的影响

摘要 目的：探讨苍附导痰汤联合通元针法对脾虚痰湿型多囊卵巢综合征（PCOS）患者脂代谢、性激素和子宫内膜容受性的影响。方法：选取2019年3月~2021年11月期间我院收治的PCOS患者87例，均辨证分型为脾虚痰湿。根据随机数字表法分为对照组（常规药物治疗，43例）和研究组（对照组基础上接受苍附导痰汤联合通元针法，44例）。对比两组临床疗效、中医证候积分、脂代谢指标、性激素指标和子宫内膜容受性变化情况。结果：研究组的临床总有效率为86.36%，高于对照组的62.79%，差异有统计学意义（P<0.05）。治疗后研究组中医证候积分较对照组低（P<0.05）。研究组治疗后的腰臀比（WHR）和体质量指数（BMI）、胰岛素抵抗指数（HOMA-IR）低于对照组（P<0.05）。研究组治疗后的卵巢体积小于对照组，内膜厚度厚于对照组（P<0.05）。研究组治疗后的黄体生成素（LH）、雌二醇（E₂）、卵泡刺激素（FSH）和抗苗勒管激素（AMH）低于对照组（P<0.05）。研究组治疗后的高密度脂蛋白胆固醇（HDL-C）高于对照组，总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）低于对照组（P<0.05）。结论：苍附导痰汤联合通元针法治疗脾虚痰湿型PCOS患者，可改善患者的脂代谢、性激素和子宫内膜容受性。     

A Single Arm Pilot Study of Effects of Berberine on the Menstrual Pattern,Ovulation Rate,Hormonal and Metabolic Profiles in Anovulatory Chinese Women with Polycystic Ovary Syndrome

Objective

To evaluate the effects of berberine on the menstrual pattern, ovulation rate, hormonal and metabolic profiles in anovulatory Chinese women with polycystic ovary syndrome.

Methods

Berberine 0.4 g three times per day was given for four months to 102 anovulatory Chinese women with polycystic ovary syndrome. The menstrual pattern, ovulation rate, hormonal and metabolic profiles were compared before and after the berberine treatment. Ovulation was confirmed by serum progesterone level ≥10ng/ml.

Results

A total of 98 of 102 subjects (96.1%) completed the four month treatment, including 69 (70.4%, 69/98) normal weight and 29 (29.6%, 29/98) overweight/obese. Fourteen women (14.3%, 14/98) had regained regular menses after berberine treatment and there was no significant difference between normal weight and overweight/obese groups. The ovulation rate was 25.0% over four months in the whole group, 22.5% in the normal weight group and 31.0% in the overweight/obese group. Sex hormone binding globulin, insulin resistance, total cholesterol, total triglyceride and low-density lipoprotein cholesterol decreased after berberine treatment in the normal weight group only.

Conclusions

Our study found that administration of berberine alone may improve the menstrual pattern and ovulation rate in anovulatory Chinese women with polycystic ovary syndrome. Berberine can also decrease sex hormone binding globulin, insulin resistance, total cholesterol, triglycerides and low-density lipoprotein cholesterol in normal weight polycystic ovary syndrome women.

Trial Registration

Chictr.org ChiCTR-OO-13003943     

Association Study between Polycystic Ovarian Syndrome and the Susceptibility Genes Polymorphisms in Hui Chinese Women

IntroductionPolycystic ovary syndrome (PCOS) is one of the most common endocrine-metabolic disorders. Evidence of familial aggregation analysis and different clinical traits among different regions and ethnicities indicated that the pathogenesis of PCOS is associated with multiple genetic and environmental factors. Our previous research had identified three susceptibility loci (rs2479106, DENND1A; rs13405728, LHCGR; rs13429458, THADA) for PCOS in Han Chinese women. The overall aim of this study was to investigate the relationship between three susceptibility gene polymorphisms and PCOS in Hui ethnic women.Methods151 patients with PCOS (case group) and 99 healthy women (control group) were recruited from the Reproductive Medicine Center of the General Hospital of Ningxia Medical University. Clinical data and serum hormone characteristics of case and control groups were collected and analyzed. The three susceptibility single-nucleotide polymorphisms have been replicated in both case and control groups. Gene polymorphisms were detected by direct sequencing after polymerase chain reaction.ResultsThe Body Mass Index, LH, LH/FSH ratio and total testosterone were significantly elevated in PCOS patients compared to control group (P<0.05). The frequencies of genotype and allele in rs13405728 were significantly different between the PCOS and the control groups (P<0.05). Of the SNP rs13405728, the PCOS cases with TT genotype stayed at a higher level of total testosterone, TG and LDL than those with the CC and CT genotypes. In contrary, there was no statistical difference between the two groups for SNP rs13429458 and rs2479106 (P>0.05).ConclusionThe present study suggested that the SNP rs13405728 in the LHCGR gene was associated with PCOS in Hui ethnic women, and its TT genotype characterized with higher level of TT, TG and LDL.     

Expression of apoptosis-related genes in the endometrium of polycystic ovary syndrome patients during the window of implantation

The present study investigated the expression of the apoptosis-related genes fas-associated via death domain (FADD) and Bcl-2 in the endometrium during the window of implantation in polycystic ovary syndrome (PCOS) patients. The aim was to explore the role of cell apoptosis in endometrial receptivity during this period. The subjects were divided into experimental and control group. The experimental group comprised 12 infertile women with PCOS, and the control group comprised 12 women who were infertile because of tubal pathological factors but had normal menstrual cycles. Endometria were collected by biopsy 7d after ovulation. Six samples from each group were randomly selected and subjected to gene chip analyses. The expression of endometrial FADD and Bcl-2 was determined by immunohistochemistry, and cell apoptosis was detected by the TUNEL method. Compared with the control group, 194 differentially expressed genes were found in the PCOS group, 102 of which were upregulated and 92 were downregulated. The differentially expressed genes were divided into 15 types according to function. Among the nine genes related to cell apoptosis, five (including Bcl-2) were upregulated and four were downregulated (including FADD). Bcl-2 expression during the window of implantation in the PCOS group increased compared with the control group, showing a significant difference (P<0.05). FADD expression in the PCOS group notably decreased compared with that in the control group, which also showed a significant difference (P<0.05). Cell apoptosis analysis showed a significant difference between the average apoptotic indices in the PCOS and control groups (P<0.05). Significant differences were observed between the endometrial gene expression in the PCOS and control groups. The decrease in cell apoptosis during the window of implantation in PCOS patients may be one of the causes of the reduced endometrial receptivity.     

二甲双胍联合枸橼酸氯米芬对多囊卵巢综合征不孕患者性激素和胰岛素水平的影响

目的:探讨二甲双胍、枸橼酸氯米芬联合治疗对多囊卵巢综合征(PCOS)不孕患者性激素和胰岛素水平的影响。方法:选取我院于2017年1月到2018年7月期间收治的101例PCOS不孕患者,采用数字表法将患者随机分为对照组(n=50)和研究组(n=51),对照组给予枸橼酸氯米芬治疗,研究组在对照组基础上联合二甲双胍治疗,采用门诊复查等方式随访6个月,记录两组患者排卵率及妊娠率,比较两组患者治疗前、治疗后的性激素、胰岛素以及血管活性因子水平,记录不良反应发生情况。结果:两组患者治疗后黄体生成素(LH)、睾酮(T)、胰岛素(INS)、LH/卵泡刺激素(FSH)均较治疗前降低,且研究组低于对照组(P0.05)。研究组排卵率、妊娠率均高于对照组(P0.05)。两组患者治疗后血管紧张素(AT-Ⅱ)、血管内皮生长因子(VEGF)均较治疗前降低,且研究组低于对照组(P0.05)。两组不良反应发生率对比无统计学差异(P0.05)。结论:二甲双胍联合枸橼酸氯米芬治疗PCOS不孕,安全有效,可有效调节患者胰岛素、性激素水平,提高排卵率、妊娠率,改善血管活性因子水平。     

新疆维汉民族多囊卵巢综合征患者CYP17基因多态性及与发病机制的关系

目的:探讨细胞色素P450酶17(CYP17)基因多态性及其与多囊卵巢综合征(PCOS)发病机制的关系。方法:选择2015年1月~2017年2月我院收治的新疆维汉民族PCOS患者260例为PCOS组,另选取同期在我院门诊检查的健康育龄妇女237例为对照组,采用限制性片段长度多态性聚合酶链反应(PCR-RFLP)技术检测两组受试者的CYP17基因多态性,比较两组等位基因及基因频率的分布,结合其临床资料分析CYP17基因多态性与PCOS发病机制的关系。结果:PCOS组体质量指数(BMI)、卵泡刺激素(FSH)水平低于对照组,黄体生成激素(LH)、睾酮(TES)及黄体生成激素与卵泡刺激素的比值(LH/FSH)高于对照组,差异有统计学意义(P0.05)。PCOS组CYP17基因A1A1、A1A2、A2A2型频率分别为34.62%、41.92%、23.46%,与对照组的34.18%、43.88%、21.94%比较差异无统计学意义(P0.05);PCOS组等位基因A1、A2频率为55.58%、44.42%,与对照组的56.12%、43.88%比较差异无统计学意义(P0.05);PCOS组不同CYP17基因型者的FSH、LH及LH/FSH水平整体比较差异无统计学意义(P0.05);PCOS组BMI水平A2A2A1A2A1A1,TES水平A2A2A1A1A1A2,差异均有统计学意义(均P0.05);对照组不同CYP17基因型者的BMI、FSH、LH、TES及LH/FSH水平整体比较差异均无统计学意义(P0.05)。结论:CYP17基因-34bp处T/C单核苷酸多态性是人群中一种常见的碱基置换,与PCOS的发病机制无明显的相关性。     

罗格列酮结合二甲双胍对多囊卵巢综合征患者胰岛素抵抗指数的影响及临床疗效

目的:探讨罗格列酮与二甲双胍联合给药对多囊卵巢综合征(PCOS)患者胰岛素抵抗指数(HOMA-IR)的变化影响与临床效果的评价。方法:回顾性选取我院收治的PCOS患者127例列为研究样本,按照用药方案差异分为两组,对照组62例采用二甲双胍进行治疗;研究组65例采用罗格列酮联合二甲双胍治疗。观察并比较两组患者治疗前后HOMA-IR、血清性激素水平、排卵率及副反应发生情况。结果:治疗后,研究组HOMA-IR低于对照组,排卵率高于对照组(P0.05);研究组患者血清E2及T水平低于对照组,而FSH及SHBG水平高于对照组(P0.05);两组患者副反应发生率比较,差异无统计学意义(P0.05)。结论:罗格列酮辅助二甲双胍治疗PCOS可显著改善患者HOMA-IR,对性激素平衡有良好作用,副作用较小。     

右归丸联合小檗碱对多囊卵巢综合征胰岛素抵抗的研究

目的:观察右归丸联合小檗碱治疗多囊卵巢综合征(PCOS)的临床疗效。方法:将114例PCOS伴胰岛素抵抗患者随机分为2组。对照组57例给予达英-35+二甲双胍,实验组57例给予右归丸联合小檗碱治疗。通过比较治疗前后的胰岛素水平(FINS)、胰岛素抵抗指数(HOMA-IR)、总胆固醇(TC)、甘油三酯(TG)、空腹血糖(FPG)、肿瘤坏死因子(TNF)及白介素-6(IL-6)水平的变化,观察右归丸联合小檗碱对PCOS胰岛素抵抗的作用疗效。结果:治疗前后实验组与对照组分别各自比较,HOMA-IR、FINS、TC、TG、TNF、IL-6显著下降,差异有统计学意义(P0.05);两组间治疗前各项指标无统计学意义(P0.05),治疗后与对照组比较,实验组TNF、IL-6水平显著下降(P0.05)。结论:右归丸联合小檗碱能显著改善患者的血脂及慢性炎症状态,最终改善胰岛素敏感性。     

ALG2 inhibits the epithelial-to-mesenchymal transition and stemness of ovarian granulosa cells through the Wnt/β-catenin signaling pathway in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects fertility in women of reproductive age, and a leading cause of anovulatory infertility. Ovarian granulosa cells are a major functional cell type in the ovary that undergo epithelial-to-mesenchymal transition (EMT) to initiate ovulation. Protein glycosylation, catalyzed by specific glycosyltransferases, has been implicated in reproductive events, such as embryo implantation, endometrial receptivity, and decidualization, etc. However, the relationship between glycosylation and EMT-mediated ovulation in PCOS is not well understood. To clarify the role of cobalt chloride (CoCl₂) and α-1,3/1,6-mannosyltransferase (ALG2) in PCOS, transwell assay, Real-time PCR, Western blot, immunofluorescence, and sphere formation assay were applied to assess cell migration, invasion, EMT, and stemness of ovarian granulosa cells. Enzyme-linked immunosorbent assay (ELISA) was performed to measure the serum level of ALG2 in PCOS patients. We found that CoCl₂ promoted the migration, invasion, EMT, and stemness of ovarian granulosa cells by downregulating the expression of ALG2. Upregulation of ALG2 rescued the effects of CoCl₂ partially, and inhibited the EMT and stemness of ovarian granulosa cells by inactivating the Wnt/β-catenin signaling pathway. Moreover, the serum level of ALG2 was increased in patients with PCOS. Elevated ALG2, in combination with testosterone, represented better diagnostic value for PCOS as a multimarker than ALG2 or testosterone alone as a single marker. Thus, ALG2, downregulated by CoCl₂, was increased in PCOS patients which inhibited the EMT and stemness of ovarian granulosa cells by deactivating the Wnt/β-catenin signaling pathway. The combination of ALG2 and testosterone might thus act as a novel but promising biomarker for PCOS detection.     

调经促孕丸联合奥利司他治疗肥胖型多囊卵巢综合征不孕的临床研究

摘要 目的：探讨调经促孕丸联合奥利司他治疗肥胖型多囊卵巢综合征（PCOS）不孕的临床疗效。方法：选取2017年6月到2019年8月期间我院收治的肥胖型PCOS不孕患者120例,按照随机数字表法将患者分为对照组（n=60）和研究组（n=60）。对照组予以奥利司他治疗,研究组在对照组的基础上联合调经促孕丸治疗,比较两组患者疗效、激素水平、排卵率、妊娠率、血糖及不良反应。结果：研究组治疗3个疗程后的临床总有效率为90.00%（54/60）,高于对照组的70.00%（42/60）（P<0.05）。两组治疗3个疗程后睾酮（T）、卵泡刺激素（FSH）、促黄体生成素（LH）均较治疗前下降,且研究组低于对照组（P<0.05）。研究组的排卵率为85%（51/60）、妊娠率为65%（39/60）均高于对照组的65%（39/60）、46.67%（28/60）（P<0.05）。两组餐后2 h血糖(2hPG)、空腹血糖（FBG）、糖化血红蛋白（HbAlc）均较治疗前下降,且研究组低于对照组（P<0.05）。两组治疗期间不良反应发生率对比未见统计学差异（P>0.05）。结论：调经促孕丸联合奥利司他治疗肥胖型PCOS不孕患者,疗效显著,可有效改善患者激素水平、血糖、排卵率、妊娠率,且不增加不良反应发生率。     

黄连素对PCOS模型大鼠LPS /NF-κB、MAPK信号通路的影响*

目的: 探讨黄连素对多囊卵巢综合征(PCOS)模型大鼠糖脂代谢、性激素结合蛋白和脂联素(LPS)以及NF-κB、MAPK信号通路的影响。方法: 将SD雌性大鼠随机分成空白组、PCOS模型组、黄连素组(0.216 g/kg)、二甲双胍组(0.135 g/kg)和达英-35(0.18 mg/kg)组,每组10只。PCOS模型组用来曲唑(1 mg/(kg·d))连续灌胃3周,随后药物干预28 d,检测大鼠体重、卵巢和子宫指数,HE染色观察大鼠卵巢卵泡数量变化,用ELISA法检测血清性激素水平、空腹葡萄糖和胰岛素、甘油三酯和胆固醇、性激素结合蛋白和脂联素水平以及用蛋白印迹法检测卵巢组织p38-MAPK、c-Jun和NF-κB蛋白表达。结果: 与空白组比较,模型组大鼠体重显著增加(P＜0.05),子宫指数显著降低(P＜0.05),囊状卵泡数量显著增加(P＜0.05),血清黄体生成素(LH)、睾酮(T)水平和LH/FSH比值显著升高(P＜0.05),卵泡刺激素(FSH)水平显著下降(P＜0.05),总胆固醇(TC)、甘油三酯(TG)、空腹胰岛素和胰岛素指数(HOMA)显著增加(P＜0.05),性激素结合蛋白(SHBG)含量显著减少以及脂联素(LPS)含量显著增加(P＜0.05),卵巢组织p38-MAPK、c-Jun和NF-κB蛋白表达上调(P＜0.05)。与模型组比较,黄连素能显著增加子宫指数(P＜0.05)、次级卵泡数量(P＜0.05),显著降低血清促黄体生成素(LH)水平、睾酮(T)水平和LH/FSH比值(P＜ 0.05),显著下调卵巢组织p38-MAPK和NF-κB蛋白表达(P＜0.05),作用类似达英-35;黄连素能明显降低血清甘油三酯(TG)、胰岛素水平和胰岛素指数(P＜0.05),升高血清SHBG水平,降低LPS水平(P＜0.05),作用类似二甲双胍。结论: 黄连素通过下调卵巢组织p38-MAPK和NF-κB蛋白表达,降低血清LPS含量,起到调控PCOS大鼠性激素紊乱和胰岛素抵抗(IR)的作用。     

LHCGR and ALMS1 defects likely cooperate in the development of polycystic ovary syndrome indicated by double-mutant mice

Polycystic ovary syndrome(PCOS) is a heterogeneous disorder with evidence of polygenetic components,and obesity may be a risk factor for hyperandrogen ism.Previous studies have shown that LHCGR is en riched in the ovary and LHCGR deficiency causes infertility without typical PCOS phenotypes.ALMS1 is implicated in obesity and hyperandrogenism,the common phenotypes among PCOS patients.Through whole-exome sequencing of 22 PCOS families and targeted candidate gene sequencing of additional 65 sporadic PCOS patients,we identified potential causative mutations in LHCGR and ALMS1 in a sibling-pair PCOS family and three sporadic PCOS patients.The expression of LHCGRL638 P in granulosa-like tumor cell line(KGN) cells promoted cyclic adenosine monophosphate production and granulosa cell proliferation,indicating that LHCGRL638 P is an activating mutation.Lhcgr~(L642 P/L642 P) mice showed an irregular estrous cycle,reduced follicles with dynamic folliculogenesis,and increased testosterone(T),estradiol(E2),and dehydroepiandrosterone.Lhcgr~(+/L642 P) AIms1~(+/PB) mice displayed increased T and E2 but decreased late secondary and preovulatory follicles.We showed that activating mutation of LHCGR likely plays important roles in the pathophysiology of PCOS involving abnormal reproductive physiology,whereas ALMS1 deficiency may promote anovulatory infertility via elevated androgens,suggesting that the disturbed LHCGR and ALMS1 cooperatively induce PCOS phenotypes,characterized as anovulation and hyperandrogenemia frequently observed in PCOS patients with obesity.     

A Model Combining Testosterone,Androstenedione and Free Testosterone Index Improved the Diagnostic Efficiency of Polycystic Ovary Syndrome

ObjectiveHyperandrogenism is frequently observed in patients with polycystic ovary (PCO). The purpose of this study was to develop an easy-to-use tool for predicting polycystic ovary syndrome (PCOS) and to evaluate and compare the value of androstenedione (Andro) and other hormone indicators in the diagnosis of patients with hyperandrogenic PCOS.MethodsThis study included 139 women diagnosed with hyperandrogenic PCOS according to the Rotterdam criteria and 74 healthy control women from Shanghai Tenth People's Hospital. The serum hormone levels of the patients and controls were measured using a chemiluminescence immunoassay and incorporated for further analysis.ResultsTotal testosterone (TT), Andro, dehydroepiandrosterone sulfate (DHEAS), and free androgen index (FAI) were significantly higher in the PCOS group than the control group. Further, Andro, follicle-stimulating hormone (FSH), luteinizing hormone (LH), TT, FAI, and LH/FSH in the hyperandrostenedione group were higher than the normal Andro group. The Youden index was the highest for Andro (0.65), with 81.82% sensitivity and 83.16% specificity. Correlation analysis showed that FSH, LH, TT, FAI, insulin sensitivity index, and LH/FSH were positively correlated with Andro, while fasting blood glucose and 2-hour postprandial blood glucose were negatively correlated with Andro.ConclusionsThe model using Andro, TT, and FAI may help to identifying women with undiagnosed PCOS. Serum Andro is a meaningful biomarker for hyperandrogenism in PCOS patients and may further aid disease diagnosis.     

Effects of metformin on the expression of GLUT4 in endometrium of obese women with polycystic ovary syndrome

The objective was to explore the effects of metformin on the expression of endometrial glucose transporter 4 (GLUT4) and analyze the related factors of GLUT4 in patients with polycystic ovary syndrome (PCOS). This study included 20 obese patients with PCOS (PCOS group) and 20 obese patients who had infertility caused by oviducal or pelvic factors but had no PCOS (control group). Follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol-2 (E(2)), testosterone (T), fasting serum glucose (FSG), fasting insulin serum (FINS), homeostasis model assessment-insulin resistance (HOMA-IR), and endometrial GLUT4 expression were determined in the two groups. In PCOS group, patients were given 500 mg of metformin three times per day for 3 mo, and then the parameters above were determined again and compared with that before metformin treatment. The parameters above also were compared between PCOS and control groups. The correlation of GLUT4 with its related factors was analyzed. The levels of T, FINS, and HOMA-IR were higher in PCOS group than in the control group (P < 0.01). The levels of protein and mRNA of endometrial GLUT4 were lower in the PCOS group than in the control group (P < 0.001). The expression of protein and mRNA of endometrial GLUT4 increased after metformin treatment (P < 0.001). HOMA-IR was negatively correlated with GLUT4 expression (P = 0.027). In patients with PCOS, the levels of protein and mRNA of endometrial GLUT4 were lower compared with that in non-PCOS women, and HOMA-IR was strongly associated with endometrial GLUT4 expression. Metformin may up-regulate endometrial GLUT4 expression to improve endometrial IR.     

定坤丹对多囊卵巢综合征患者性激素水平、胰岛素抵抗及妊娠情况的影响

目的:探讨定坤丹对多囊卵巢综合征患者性激素水平、胰岛素抵抗及妊娠情况的的影响。方法:选择2016年5月至2018年5月我院收治的210例多囊卵巢综合征患者,根据随机化原则将其分为两组,每组105例。对照组患者接受达英-35与二甲双胍治疗,研究组在对照组的基础上口服定坤丹治疗。连续治疗3个月后,比较两组治疗前后的性激素水平及胰岛各相关指标的变化。治疗结束后随访1年,比较两组的排卵及妊娠情况。结果:与治疗前相比,两组治疗后的血清睾酮(Testosterone,T)、黄体生成素(Luteinizing hormone,LH)及LH/FSH均明显降低,且研究组以上指标均显著低于对照组(P<0.05)。两组治疗前后的卵泡刺激素(Follicle-stimulating hormone,FSH)水平比较无统计学差异(P>0.05)。与治疗前相比,两组治疗后的空腹胰岛素(Fasting insulin,FINS)、餐后2 h胰岛素(Postprandial 2 hours insulin,2hPINS)及β细胞胰岛素分泌功能(Homeostasis model assessment ofβcell,HOMA-β)均明显升高,胰岛素敏感指数(Homeostasis model assessment-Insulin sensitivity index,HOMA-IS)明显降低,且研究组以上指标较对照组改善更明显(P<0.05)。研究组排卵及成功妊娠率均显著高于对照组(P<0.05)。结论:定坤丹有助于改善多囊卵巢综合征患者性激素水平及胰岛素抵抗,提高排卵及妊娠率。     

Inhibition of CYP450 1A and 3A by berberine in crucian carp Carassius auratus gibelio

Berberine has long been considered as an antibiotic candidate in aquaculture. However, studies regarding its effects on drug-metabolizing enzymes in fish are still limited. In the present study, the effects of berberine on cytochrome P4501A (CYP1A) and CYP3A in crucian carp were investigated. Injection of different concentrations of berberine (0, 5, 25, 50, and 100 mg/kg) inhibited the CYP1A mRNA expression, thereby inhibiting further the catalytic activity of CYP1A-related ethoxyresorufin-O-deethylase (EROD). Furthermore, both CYP1A expression and EROD activity were further inhibited with increasing berberine concentrations. In addition, the CYP3A expressions at both the mRNA and the protein levels were downregulated by higher berberine concentrations. The catalytic activity of CYP3A-related erythromycin N-demethylase (ERND) was also inhibited by berberine at a dose of no less than 25 mg/kg. Moreover, at the berberine concentration exceeding 25 mg/kg, the inhibition of CYP3A expression and ERND activity increased with increasing berberine concentrations. In vitro experiments were also performed. When berberine was pre-incubated with the crucian carp liver microsomes, it competitively inhibited the corresponding EROD activity with the IC₅₀ of 11.7 μM. However, the ERND activity was slightly inhibited by berberine with the IC₅₀ of 206.4 μM. These results suggest that, in crucian carp, berberine may be a potent inhibitor to CYP1A, whereas the CYP3A inhibition needs a higher concentration of berberine.