目的:基于中医传承辅助平台软件,分析总结国医大师何成瑶教授辨治输卵管性不孕的用药规律.方法:收集并规范国医大师何成瑶教授门诊收治输卵管性不孕患者病例数据,通过频次分析、关联规则、聚类分析等方法对病例进行数据挖掘和可视化分析,明确核心组方并挖掘潜在新处方.结果:分析纳入的65例病案得出101味中药,当归、甘草、牡丹皮、赤芍、川芎、白芍、茯苓、大血藤、金银花等使用频次最高,所用中药性味多为苦、甘、辛,主要归肝、心、脾、肾四经.通过关联规则分析,得到核心药物组合19条及新方5首.结论:国医大师何成瑶教授治疗输卵管性不孕以活血通络为主,辅以疏肝清热,补肾宁心.

目的 分析解脲支原体(UU)、沙眼衣原体(CT)感染对慢性盆腔炎(CPID)病情及阴道菌群的影响.方法 选取 2019 年 1 月-2022 年 11 月在贵州中医药大学第二附属医院妇科就诊的 185 例 CPID患者为病例组,随机选取同期 150 名女性健康体检者为对照组,对两组研究对象的 UU、CT感染情况及阴道炎症情况、阴道菌群情况进行分析.结果 病例组 UU、CT感染比例均高于对照组(P＜0.05),两组研究对象各类阴道炎的患病率比较,无统计学差异.病例组阴道菌群密度、菌群多样性以Ⅰ级或Ⅳ级为主,乳杆菌分级以Ⅱb 级为主,对照组阴道菌群密度、菌群多样性以Ⅱ级或Ⅲ级为主,乳杆菌分级以Ⅱa级为主;病例组阴道微生态异常的比较高于对照组,差异均有统计学意义(P＜0.05);与未感染 UU或CT的患者相比较,病例组中感染 UU 或 CT 患者的病情程度以重度为主,阴道菌群密度和阴道菌群多样性中Ⅰ级或Ⅳ级较多,阴道微生态异常比例较高,差异均有统计学意义(P＜0.05).结论 CPID患者具有较高的 UU、CT感染率和明显的阴道菌群异常,感染 UU 或 CT 患者的病情和阴道微生态异常更加严重,UU、CT等非细菌性病原微生物的感染可能在CPID发生和发展机制中发挥了重要的作用.

总结何成瑶教授治疗子宫内膜异位症合并崩漏经验.何成瑶教授认为内异症的发病以肾虚血瘀为主,气滞、痰湿、寒凝等均为致病因素.治疗上以"养精育胞"为理论原则,建立"宁心坚肾、温枢三焦"的治法.

目的 探讨淫羊藿苷(ICA)对早发性卵巢功能不全(POI)大鼠卵巢结构、功能的影响及可能作用机制.方法 从55只SPF级雌性SD大鼠中随机选取10只动情周期正常的大鼠作为对照组,剩余大鼠经腹腔注射环磷酰胺制备POI模型,成模大鼠随机分为模型组、ICA低(15 mg·kg-1)、中(30 mg·kg-1)、高(60 mg·kg-1)剂量组,对照组及模型组大鼠每日灌胃等量生理盐水,连续28 d.计算各组大鼠卵巢湿重和卵巢指数;HE染色观察卵巢组织结构;TUNEL染色检测颗粒细胞凋亡率;ELISA法检测血清促卵泡激素(FSH)、雌二醇(E2)、抗苗勒管激素(AM H)、丙二醛(MDA)及超氧化物歧化酶(SOD)含量;RT-qPCR技术检测磷脂酰肌醇3-激酶(PI3K)、蛋白激酶B(Akt)、哺乳动物雷帕霉素靶蛋白(mTOR)、核糖体S6蛋白激酶1(S6k1)mRNA相对表达量;Western blot法检测PI3K、Akt、mTOR和S6k1蛋白活性水平及B细胞淋巴瘤/白血病-2基因(Bcl2)、Bcl2相关X蛋白(Bax)和Cleaved Caspase-3蛋白相对表达情况.结果 成功诱导POI大鼠模型;与对照组比较,模型组及ICA低、中、高剂量组大鼠卵巢湿重、卵巢指数、成熟卵泡和黄体数、血清E2、AMH及SOD水平降低,闭锁卵泡数、颗粒细胞凋亡率、血清FSH、MDA水平升高,卵巢见有不同程度萎缩,卵泡结构、形态见有不同程度退化,另卵巢组织中Bax、Cleaved Caspase-3蛋白相对表达量升高,Bcl2蛋白相对表达量降低,PI3K、Akt、mTOR、S6k1 mRNA及其蛋白活性水平降低(P＜0.05);与模型组比较,ICA低、中、高剂量组大鼠上述指标及因子水平均逆转(P＜0.05);ICA作用效果呈剂量依赖性(P＜0.05).结论 ICA可提高POI大鼠血清E2水平,降低FSH水平,改善POI大鼠卵巢结构及卵巢储备功能,其作用机制可能与激活PI3K/Akt/mTOR通路有关.

Premature ovarian insufficiency (POI) is characterized by the loss of ovarian function before 40 years of age and affects approximately 1% of women worldwide. Caragana sinica is a traditional Miao (a Chinese ethnic minority) medicine that improves ovarian function and follicular development. In the present study, we aimed to investigate the effect of active ingredients of C. sinica on POI and determine underlying mechanisms. Herein, the chemical composition of the C. sinica compound was analyzed using ultra-high-performance liquid chromatography, which identified hyperin (HR) as one of the main ingredients in C. sinica. Then, interaction targets of HR and POI were predicted and analyzed using network pharmacology and bioinformatics. The effect of HR on triptolide (TP)-induced granulosa cell injury was evaluated, and the underlying mechanism was explored based on bioinformatic results. A total of 100 interaction targets for POI and HR were obtained. The protein-protein interaction network of identified interaction targets emphasized the topological importance of AKT1. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that HR might regulate POI by modulating the mechanistic target of rapamycin (mTOR) signaling pathway. In addition, the KEGG graph of the mTOR signaling pathway revealed that AKT phosphorylation inhibits the TSC1/2, while TSC1/2 activation inhibits the expression of mTORC1. The fundamental experiment revealed that HR increased proliferation, progesterone receptor levels, and estradiol levels decreased by TP in KGN cells. Additionally, HR alleviated TP-induced apoptosis and G1/G1 phase arrest in KGN cells. Western blotting demonstrated that HR increased the phosphorylation of AKT and mTORC1 and decreased TSC1 expression in TP-induced KGN cells. Collectively, our findings revealed that HR alleviates TP-induced granulosa cell injury by regulating AKT/TSC1/mTORC1 signaling, providing insight into the treatment of POI.

不孕症是妇科的常见病,近年来全世界的不孕症发生率有增加的趋势.现代中医在继承前辈中医理论的基础上,利用现代科学技术及检查手段,采用更有针对性的药物,往往能取得更好的效果.全国名老中医何成瑶教授在中西医结合诊治方面从事妇科临床医疗和科研工作多年,有丰富的临床经验,在治疗不孕症的过程中,以主诉为主线,以西医的病名、定义、检查手段来明确诊断,在此基础上以中医中药为主进行中医的辨证论治来对症治疗,在临床中取得了较好的疗效,为此本文总结何成瑶教授治疗排卵障碍性不孕证的经验,提高临床知识.

目的:分析脐带间充质干细胞对卵巢早衰家兔的治疗效果及机制研究.方法:经腹腔连续注射2 d环磷酰胺50 mg/(kg·d)建立卵巢早衰家兔模型.将建模成功的10只家兔随机分成模型组和治疗组,每组5只.建模一周后,治疗组家兔每天经耳缘静脉注射5x 106/mL脐带间充质干细胞混悬液2mL,连续注射3d.模型组家兔经耳缘静脉注射等量无菌生理盐水.于治疗后0d、7d、14d和28 d,取家兔静脉血检查血清激素表达水平.于治疗后28 d,检测家兔卵巢中生长卵泡数、封闭卵泡数、黄体数、富半胱氨酸蛋白61(CYR61)和结缔组织生长因子(CTGF)mRNA及蛋白质相对表达量.结果:治疗前,模型组和治疗组家兔血清雌二醇(E2)、促卵泡生成素(FSH)、FSH/黄体生成素(LH)、抑制素B(INHB)和抗苗勒管激素(AMH)、均无显著差异(P＞0.05).与模型组相比,治疗后治疗组家兔血清E2和INHB水平显著上升(P＜0.05),FSH水平显著下降(P＜0.05),FSH/LH均无显著差异(P＞0.05).随着治疗时间延长,治疗组家兔血清E2和FSH水平周期性波动.治疗28 d后,与模型组相比,治疗组家兔血清AMH水平显著升高(P＜0.05);卵巢组织中CYR61和CTGF mRNA及蛋白质相对表达量均显著升高(P＜0.05);生长卵泡数显著升高(P＜0.05);封闭卵泡数和黄体数均显著降低(P＜0.05).结论:静脉注射脐带间充质干细胞可通过上调CYR61和CTGF的表达,促进卵泡生成,恢复卵巢功能,达到治疗卵巢早衰的临床效应.

何成瑶教授在临床诊疗中认为不孕症常与肾虚、肝郁、痰湿、血瘀有关,治疗上以补肾疏肝、调经种子为主,兼以活血化瘀、燥湿化痰、养血调经,并自拟经验方辨证加减,获得较好临床效果.本篇文章主要从病因病机及病案进行归纳,总结何成瑶教授对女性不孕症的辨治经验特色.

子宫腺肌病属于子宫内膜异位症的一种,临床表现以进行性痛经、经期延长为主,甚至导致不孕.现代医学认为该病的病因主要是子宫内膜腺体及间质部分种植在子宫肌层,肌纤维结缔组织增生,并且在性激素影响下随月经周期变化脱落.该文主要介绍何成瑶教授运用自拟妇科调经2号方治疗子宫腺肌病合并不孕症的临床经验.

随着社会的发展,人们性观念改变,婚前性行为日益增加,婚前人流史的人增加,输卵管性不孕症患者数量也不断上升,因此积极治疗输卵管性不孕意义重大.何成瑶教授认为肾虚瘀积是导致本病的主要原因.临床上以补肾调经,活血祛瘀,通络散结为法治疗输卵管炎所导致的不孕,收效甚显.本文从发病机理、辨证论治、基本方药、典型病案等方面进行整理,归纳总结何成瑶教授治疗肾虚血瘀型输卵管性不孕的学术思想及临床经验.

月经周期不同阶段肾阴阳消长以及气血盈亏有一定的变化规律,月经病重在调整月经周期,针灸辨证分期治疗月经病具有独特的优势,本文总结了首届全国名中医何成瑶教授针灸调整月经周期的临证经验,何教授认为经后以补肾益气、调节阴阳;经间期重阴必阳,此时应抓住时机,因势利导,促进阴阳转化;经前期阳气渐盛,阴气未衰,应阴中求阳,补火助阳.

目的 研究更年汤对围绝经期模型大鼠颗粒细胞磷脂酰肌醇-3激酶(PI3K)/蛋白激酶B(Akt)/哺乳动物雷帕霉素蛋白(mTOR)信号通路的影响.方法 10～14月龄雌性SD大鼠150只,筛选出围绝经期模型大鼠,随机分为模型组、替勃龙组(0.22 mg/kg)和更年汤低、中、高剂量(1.0、2.0、4.0 g/kg)组,连续ig给药15d,1次/d,第15天后采血,制备大鼠含药血清;3～4月龄雌性SD大鼠120只,筛选出动情前期老鼠,剔出卵巢行体外颗粒细胞原代培养,分别用各组含药血清培养液培养颗粒细胞,72～120 h后用实时荧光定量PCR (qRT-PCR)检测颗粒细胞中PI3K、Akt、mTOR、生长分化因子9 (GDF9)、翼状螺旋转录因子2(FOXL2) mRNA表达水平;Western blotting法检测PI3K、Akt、mTOR、GDF9、FOXL2蛋白表达.结果 与模型组比较,替勃龙组和更年汤各剂量组卵巢颗粒细胞中PI3K、mTOR mRNA和蛋白表达水平均显著升高(P＜0.05、0.01),Akt mRNA和蛋白表达水平显著降低(P＜0.05、0.01),GDF9、FOXL2 mRNA和蛋白表达水平均显著降低(P＜0.01).结论 更年汤含药血清在临床剂量上可提高卵巢颗粒细胞PI3K、mTOR的表达,抑制Akt及其下游的GDF9、FOXL2表达,从而推测更年汤可调节卵泡的生长发育,抑制卵泡闭锁、改善卵巢功能.

输卵管堵塞导致的不孕占女性不孕的35％以上[1].目前,西医治疗主要是手术治疗,但是由于手术创伤较大,手术治疗后患者恢复慢,加用中医治疗能明显提高患者输卵管再通率及受孕率.本文介绍1例输卵管堵塞导致的不孕患者在经过两次手术治疗后加予中药保留灌肠随访13年成功诞下1子1女病例,结合文献分析名老中医经验方保留灌肠治疗不孕症的疗效及中西医结合治疗不孕症的优势.

现代女性生活工作压力较大,对自身生活质量要求日渐提高,使得以经前乳房胀痛为主诉的病人渐多见,何教授博览经典,临床经验丰富,在治疗经行乳房胀痛有卓见,以调肝通络为妙,同时注重心理疏导,疗效显著。

OBJECTIVE: To investigate the efficacy of self-made Gengnian decoction on expressions of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt) and mammalian target of rapamycin (mTOR) in ovarian tissues of perimenopausal rats. They were identified with symptom pattern of kidney-Yang deficiency in terms of Traditional Chinese Medicine. METHODS: Female Sprague-Dawley rats aged 10-12 months were selected. Estrous cycle was observed by vaginal smears of keratinocytes to screen the perimenopausal model rats. The chosen rats were randomly divided into five groups, including perimenopausal model of kidney-Yang deficiency group (24 rats), self-made Gengnian decoction of high-dose group (24 rats), self-made Gengnian decoction of middle-dose group (24 rats), self-made Gengnian decoction of low dose group (24 rats) and tibolone control group (24 rats). In addition, rats aged 4-6 months were selected as young control group. The perimenopausal model rats of kidney-Yang deficiency were prepared by alternative intramuscular injection of hydrocortisone 5 mg . kg(-1).d(-1) The successfully prepared models in self-made Gengnian decoction of high-dose, middle-dose and low-dose groups and tibolone control group were given self-made Gengnian decoction 26.4, 13.2 and 6.6 mg . kg(-1).d(-1), and tibolone tablets solvent 0.22 mg . kg(-1).d(-1), respectively, through intragastric administration. Models group and young control group were given the same dose of normal saline, 1 time a day for 15 consecutive days. 24 h after the last administration, blood and ovarian tissues were collected after anesthesia with 20% ethyl carbamate. The follicles of different levels in ovarian tissue were observed and counted by histopathological hematoxylin-eosin staining. Enzyme linked immunosorbent assay was applied to test insulin-like growth factor-1 (IGF-1) level in the serum of experimental rats. The expression levels of PI3K, phosphorylated-Akt (p-Akt) and phosphorylated-mTOR (p-mTOR) mRNA in ovarian tissue were detected by quantitative real-time polymerase chain reaction. RESULTS: The total follicle counts of perimenopausal model rats with kidney-Yang deficiency were significantly reduced, and the number of follicles (mainly increased in preantral follicles and antral follicles) in perimenopausal model rats with kidney-Yang deficiency was significantly increased after intervention of high and middle doses of Gengnian decoction and tibolone (P < 0.05). Compared with normal rats in young control group, the levels of IGF-1 in serum of perimenopausal rats with kidney-Yang deficiency were significantly decreased (P < 0.01), and those intervened by high dose of Gengnian decoction and tibolone were significantly up-regulated. The relative expression levels of PI3K, p-Akt, p-mTOR mRNA in ovarian tissues of perimenopausal rats with kidney-Yang deficiency were significantly lower than those of young rats (P < 0.01), and those intervened by high dose of Gengnian decoction and tibolone were significantly up-regulated (P < 0.05). CONCLUSION: Self-made Gengnian decoction can increase the levels of IGF-1, PI3K, Akt and mTOR mRNA expression in serum. (C) 2019 JTCM. All rights reserved.

目的:探讨自拟更年汤对肾阳虚围绝经期模型大鼠卵巢功能的影响.方法:选取10～12个月龄雌性SD大鼠,采集阴道脱落细胞筛选出围绝经期模型大鼠,将围绝经期模型大鼠随机分为模型组、更年汤低剂量组、更年汤中剂量组、更年汤高剂量组、替勃龙组,每组24只,构建肾阳虚模型;另选24只4～6个月龄的青年大鼠为青年组;各组分别给予相应药物灌胃,末次给药24h后,检测血清中卵泡刺激素(FSH)水平及卵巢组织中FSHR、IGF-1以及其受体蛋白表达.结果:更年汤高剂量组、更年汤中剂量组、替勃龙组大鼠血清FSH水平明显低于模型组(P＜0.05或P＜0.01),卵巢组织中FSHR、IGF-1及其受体表达明显高于模型组(P＜0.05或P＜0.01).结论:更年汤能改善肾阳虚围绝经期模型大鼠卵巢功能,可能与调节大鼠血清中FSH水平,调节大鼠卵巢组织中FSH、IGF-1及其受体的表达有关.

目的 总结何成瑶教授治疗卵巢型内异症引起不孕的治疗经验及特色;方法 门诊跟师学习总结何老治疗该病的经验及特色.结论 何成瑶教授采用清热祛瘀法治疗卵巢型内异症引起的不孕症疗效颇佳.

总结何成瑶教授治疗崩漏的临床经验.通过门诊跟师学习总结何老治疗该病的经验及特色.何成瑶教授根据辨证论治采用分期用药方法治疗崩漏,临床疗效显著.

目的:探讨肾阳虚围绝经期模型大鼠在自拟更年汤不同剂量干预下对卵巢PI3K/AKT/mTOR蛋白表达的影响.方法:选24只4～6月龄的青年大鼠作为对照组,构建肾阳虚模型.另采集阴道脱落细胞将10～12月龄雌性SD大鼠筛选出围绝经期模型,并将该模型大鼠随机分为模型组、利维爱组、更年汤低、中及高剂量共5组,每组24只.以上6组均给予相应药物灌胃,末次给药24 h后,检测卵巢组织中IGF-1、IGF-1R及PI3K/AKT/mTOR蛋白表达.结果:更年汤高剂量组、西药组IGF-1、IGF-1R及PI3K/AKT/mTOR蛋白表达均较高,与模型组比较均有统计学差异(P<0.05).结论:更年汤能改善肾阳虚型围绝经期模型大鼠卵巢组织中PI3K/AKT/mTOR蛋白表达,可能与能调节IGF-1及其受体的表达量有关.

人类社会化进程,构成人类的疾病种类、疾病的病因及死亡原因也随之发生改变,随着人类物质生活条件的改善,对健康的需求也有了更多元化的需求,新医学模式随之诞生,妇产科技能训练如何适应新医学模式及现代教育发展,培养适合我国的国情的新时代高级医学人才,本文从医学文人素质培养、医学模拟教学方面进行探讨.