子宫内膜功能亢进性疾病的“异病同治”诊治研究思路＊

笔者根据现代临床子宫内膜的病理演变过程结合中医“异病同治”理念，提出“子宫内膜功能亢进性疾病”概念，涵盖5种常见的子宫内膜疾病：无排卵性异常子宫出血（Abnormal Uterine Bleeding Ovulatory dysfunction，AUB-O），子宫内膜息肉（Endometrial Polyp，EP），子宫内膜异位症（Endometriosis，EMs），子宫腺肌病（Adenomyosis，AM），子宫内膜癌（Endometrial Carcinoma，EC）。基于文献的汇总，分析得到此类疾病的子宫内膜病理演变与中医病因病机的关联性，为寻找关键通路、创新性治疗此类疾病提供了重要的参考方向，对深化中医妇科学常见疾病的共性病因病机提供了理论依据和探索思路。     

A novel CDKN1A-JAZF1 gene fusion in low-grade endometrial stromal sarcoma arising from endometriosis in abdominal wall cesarean section scar: A case report and literature review

ObjectiveWe report a low-grade endometrial stromal sarcoma (ESS) with a novel CDKN1A-JAZF1 fusion gene arising from abdominal wall endometrioma.Case reportA 40-year-old woman presented with a 5.5-cm abdominal wall mass juxtaposed to the postoperative scar of two cesarean sections. Histologically, the tumor exhibited obvious tongue-like protrusions into the surrounding tissue, showed spindle cells with multinodular growth pattern that occasionally rotate around small arteries. Immunohistochemically, the tumor cells were positive for CD10, estrogen receptor (ER), progesterone receptor (PR), negatively stained for smooth muscle actin (SMA), CD117, CyclinD1. In addition, a previously undescribed gene fusion between CDNK1A 5′ end of exon 1(NM_000389.5) and JAZF1 3′ end of exon 5 (NM_175,061,3) was reported in this case.ConclusionThis report of ESS suggesting that rapidly growing abdominal wall masses without menstruation-related should be promptly evaluated and treated aggressively. In addition, we have expanded the molecular landscape of low-grade ESS.     

Uso de inhibidores de la aromatasa en el tratamiento del dolor pélvico asociado a endometriosis: revisión sistemática

ObjectiveTo know the effect of the use of aromatase inhibitors (AI) in the treatment of endometriosis-associated pelvic pain (EAPP).Material and methodsSystematic review of the literature.Results173 articles were identified of which 25 were valid for the review, of which 4 were randomized clinical trials, 3 were non-randomized clinical trials, 10 were prospective non-comparative studies and 8 were clinical case reports. In most of the studies and/or case reports (24 of 27) the use of AI was associated with an improvement in EAPP. Important biases were identified that may influence the efficacy analysis, primarily the combined use of AI with other drugs widely used in the treatment of endometriosis.ConclusionsDespite the existence of numerous articles presenting and/or analysing the effect of AIs in the control of EEAP, the biases in the interpretation of their results, together with the side effect profile of this group of drugs, mean that their use has not become widespread, and they continue to be considered an experimental treatment for endometriosis. To date, there is insufficient evidence of sufficient quality to recommend the use of AI in the treatment of EEAP in routine clinical practice.     

Promising activity of Anthemis austriaca Jacq. on the endometriosis rat model and isolation of its active constituents

Anthemis austriaca Jacq. flowers are traditionally used to alleviate abdominal pain, hemorrhoids, ovary diseases and pneumonia. This study aimed to investigate the effects of A. austriaca flowers, which are frequently used in gynecological disorders, on the rat endometriosis model. The rat endometriosis model was used to evaluate the potential activity of the plant in endometriosis. The dried plant material was extracted with n-hexane, ethyl acetate (EtOAc), and methanol (MeOH), successively. The obtained extracts from A. austriaca flowers were applied to the rats. The adhesion scores, endometrial foci areas, and cytokine levels of the peritoneal fluids were measured on surgical induction of endometriosis in rats. The adhesion scores, endometriotic volume, and cytokine levels of the peritoneal fluids were reduced in the EtOAc, MeOH, and buserelin acetate-treated (reference) groups. The MeOH extract reduced the adhesion scores and endometrial foci areas from 3.1 to 1.1 (p < 0.01) and from 86.4 to 40.5 (p < 0.01), respectively and also the MeOH extract reduced tumor necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), and interleukin (IL)-6 levels of the peritoneal fluids from 13.7 to 3.8 (p < 0.01), from 28.4 to 16.3 (p < 0.05) and from 50.2 to 24.3 (p < 0.01), respectively. Therefore, isolation studies were conducted on the EtOAc and MeOH extracts. After the MeOH extract was fractionated using RP-18 column, the obtained subfractions were evaluated again on the endometriosis rat model. Subfractions A and C of the MeOH extract displayed statistically significant activity on the endometriosis rat model. Phytochemical investigation resulted in the isolation of 4-β-D-glucopyranosyloxy-6-methyl-2H-pyran-2-one (1) from Fr. A and quercetin (2), apigenin-7-O-(3″-O-acetyl)-β-D-glucopyranoside (3), apigenin-7-O-(6″-O-acetyl)-β-D-glucopyranoside (4), apigenin-7-O-β-D-glucopyranoside (5), quercetin-7-O-β-D-glucopyranoside (6) from Fr. C. Moreover, β-sitosterol-3-O-β-D-glucopyranoside (7) was isolated from the EtOAc extract. As a conclusion, the MeOH extract obtained from A. austriaca flowers contributed to the regression of endometriosis. In addition, flavonoids and sterols of the plant were detected as the possible compounds responsible for the activity.     

基质金属蛋白酶在子宫内膜异位症患者中的表达水平及在盆腔粘连中的作用

目的分析基质金属蛋白酶(MMPs)在子宫内膜异位症患者中的表达水平及在盆腔粘连中的作用。方法选取2017年1月-2018年12月在温州市人民医院进行腹腔镜手术的60例子宫内膜异位症患者为观察组,选取同期进行腹腔镜手术的30例非子宫内膜异位症患者为对照组。观察组根据术中盆腔粘连程度分为1组(无或仅有轻度盆腔粘连,子宫内膜异位症Ⅰ~Ⅱ期,24例)和2组(中重度盆腔粘连,子宫内膜异位症Ⅲ~Ⅳ期,36例)。采集3组腹腔液和血清,采用ELISA法检测腹腔液及血清基质金属蛋白酶-2 (MMP-2)、基质金属蛋白酶-3 (MMP-3)、基质金属蛋白酶-7 (MMP-7),血清雌二醇(E2)、黄体生成素(LH)、孕酮(P)、卵泡刺激素(FSH),白细胞介素-6 (IL-6)、白细胞介素-8 (IL-8)、肿瘤坏死因子-α(TNF-α)、C-反应蛋白(CRP)水平。结果 1组腹腔液MMP-2、MMP-3、MMP-7水平显著高于对照组,差异有统计学意义(均P<0. 05),2组腹腔液MMP-2、MMP-3、MMP-7水平显著高于1组(均P<0. 05)。1组血清FSH、LH水平显著高于对照组(均P<0. 05),2组血清FSH、LH水平显著高于1组(均P <0. 05)。1组血清E2、P水平显著低于对照组(均P<0. 05),2组血清E2、P水平显著低于1组(均P<0. 05)。1组血清IL-6、IL-8、TNF-α水平显著高于对照组(均P<0. 05),2组血清IL-6、IL-8、TNF-α水平显著高于1组(均P<0. 05)。结论子宫内膜异位症患者腹腔液中MMPs水平升高,可能与盆腔粘连的发生及严重程度相关。     

穴位埋线对肾虚血瘀型子宫内膜异位症患者IL-1β、TNF-α、VEGF和MMP-2水平的影响

目的:基于PI3K/Akt/mTOR信号通路,探讨穴位埋线疗法治疗肾虚血瘀型子宫内膜异位症的临床疗效及对IL-1β、TNF-α、VEGF和MMP-2等相关信号通路下游细胞因子的水平的影响。方法:选取肾虚血瘀型子宫内膜异位症的门诊和住院患者86例,按照随机数字表法随机分为穴位埋线组和西药组,西药组口服孕三烯酮胶囊(内美通),穴位埋线组在西药组的基础上采用穴位埋线进行治疗,治疗3个月后观察两组患者的临床疗效和IL-1β、TNF-α、VEGF、MMP-2等相关信号通路下游细胞因子的水平。结果:治疗后穴位埋线组总有效率93.02%(40/43),西药组总有效率83.72%(36/43),两组比较差异无统计学意义(P>0.05)。治疗3个月后,穴位埋线组和西药组的VAS评分、血清IL-1β、TNF-α、VEGF和MMP-2水平均较治疗前改善(P<0.01),但穴位埋线组较西药组改善更为明显(P<0.05或P<0.01)。治疗过程中,西药组不良反应发生率为18.60%(8/43),穴位埋线组不良反应发生率为4.65%(2/43),两组不良反应发生率比较,差异有统计学意义(P<0.05)。结论:穴位埋线可以显著改善子宫内膜异位症患者的临床症状和体征,并能显著降低孕三烯引起的不良反应,可见穴位埋线疗法可以作用PI3K/Akt/mTOR信号通路,通过改善通路下游的IL-1β、TNF-α、VEGF和MMP-2水平,发挥治疗子宫内膜异位症的作用。     

少腹逐瘀汤联合孕三稀酮治疗子宫内膜异位症前瞻性研究

目的:探讨少腹逐瘀汤联合西药保守治疗子宫内膜异位症的临床价值。方法:我院诊治的80例子宫内膜异位症患者为研究对象,按随机双盲分组原则分为观察组和对照组,各40例。两组均给予孕三稀酮进行治疗,观察组在此基础上加用少腹逐瘀汤。对比两组临床疗效,记录两组治疗前后中医症状评分、血液流变学(血浆黏度、全血高切黏度、全血低切黏度、红细胞沉降速率、红细胞聚集指数、纤维蛋白原)及外周血糖类抗原125(CA125)含量,并观察两组在治疗期间不良反应发生情况。结果:观察组临床总有效率90.00%显著高于对照组72.50%,差异有统计学意义(P<0.05)。两组治疗后痛经、腰骶肛门坠胀、月经周期、经期、形寒肢冷症状评分较治疗前显著降低(P<0.05); 观察组治疗后痛经、腰骶肛门坠胀、月经周期、经期、形寒肢冷症状评分显著低于对照组(P<0.05)。观察组治疗后血液流变学指标及外周血CA125含量显著低于对照组(P<0.05)。结论:采用少腹逐瘀汤联合孕三稀酮治疗子宫内膜异位症,能提高临床疗效,减轻患者临床症状,加快病情康复。     

Clinical characteristics and pregnancy outcomes of infertile patients with endometriosis and endometrial polyps: A retrospective cohort study

ObjectiveThe aim of this study was to discuss the clinical characteristics and the prognosis of surgically diagnosed endometriosis complicated by endometrial polyps and investigate the association between pregnancy outcomes during subsequent pregnancies.Materials and methodsFrom January 2013 to December 2016, 1263 infertile patients were enrolled in the study. We identified 451 patients with endometriosis, and divided them into a polyp group (n = 204) and a non-polyp group (n = 247) based on whether or not they were associated with endometrial polyps. Postoperative clinical pregnant women (n = 82) among the polyp group were then classified into a study group and a control group composed of those undergoing a singleton pregnancy (n = 164) who delivered during the same time period. Clinical statuses and complications during pregnancy and delivery were collected from hospitals and by telephone interviews and surveys through the mail.ResultsThe prevalence rate of endometriosis infertile group was obviously higher than the non-endometriosis infertile group ([45.23%; 204/451] versus [17.12%; 139/812]). Women suffering from stage 1 to 4 endometriosis had a 42.44% (73/172), 40.69% (59/145), 55.89% (38/68) and 51.52% (34/66) occurrence rate of endometrial polyps, respectively. The frequency of endometrial polyps for stage 3 and 4 patients was obviously higher than that of stage 1 and 2 patients ([53.73%; 72/134] versus [41.64%; 132/317]). Moreover, the occurrence rate of deep infiltrating endometriosis (DIE) was 57.81% (37/64), which was obviously higher than that of ovarian endometriosis (42.42%; 98/231) and peritoneal endometriosis (44.23%; 69/156). Of the 204 women diagnosed with posterior endometrial polyps, 89 became pregnant, 7 pregnancies ended in a spontaneous abortion, and 82 successfully delivered a baby. The clinical pregnancy rate of patients in stages 1 and 2 was wholly higher than that of patients in stages 3 and 4 ([48.70%; 56/115] versus [37.71%; 26/82]). The postsurgical pregnancy status of patients suffering from peritoneal endometriosis was slightly better than those with ovarian or DIE, but differences were not statistically significant (P = 0.626). We also found that the pregnancy rate was statistically elevated in patients whose EFI scores range from 7 to 10. When compared to the control group, women with endometriosis and endometrial polyps had a higher risk of their pregnancy being complicated by placenta previa (13.41%) and cesarean delivery (59.76%).ConclusionPatients with endometriosis have a higher frequency of endometrial polyps. We found that a combined hysteroscopy and laparoscopy surgical procedure is an effective way to increase pregnancy rates. Different endometriosis stages and types in patients were associated with clinical pregnancy and spontaneous abortion rates. Women affected by both endometriosis and endometrial polyps have an independently elevated risk of placenta previa and cesarean delivery during pregnancy.