腹腔镜联合促性腺激素释放激素激动剂治疗子宫内膜异位症伴不孕症的疗效观察

目的:探讨腹腔镜与促性腺激素释放激素激动剂(Gn RH-a)联合治疗子宫内膜异位症(EMS)伴不孕症的临床疗效。方法:选择2012年1月~2014年12月期间我院收治的108例EMS伴不孕症患者作为研究对象,随机分为研究组与对照组,每组各54例。对照组患者采用腹腔镜治疗,研究组在此基础上于术后应用达菲林治疗。两组均行宫腔镜检查,观察两组临床疗效,1年内的妊娠率、复发率及两组患者治疗前后血浆雌二醇(E2)及卵泡刺激素(FSH)水平变化。结果:研究组治疗总有效率为98.15%,显著高于对照组的85.19%(P0.05);两组1年内复发率对比差异无统计学意义(P0.05);研究组1年内妊娠率为55.56%,高于对照组的27.78%(P0.05)。研究组治疗后E2、FSH显著低于对照组及治疗前(P0.05)。结论:腹腔镜联合Gn RH-a治疗EMS伴不孕症应用效果显著,可以有效改善患者的临床症状,提高妊娠率。     

黄体酮对子宫内膜异位症在位内膜预处理与IVF治疗结局关系

摘要 目的：研究黄体酮对子宫内膜异位症在位内膜预处理改善IVF结局。方法：男性因素并卵巢子宫内膜异位囊肿168例,分两组：（1）实验组：IVF前自然周期月经第12天地屈孕酮30 mg/日、14天,3个月;（2）对照组：IVF前无干预。IVF前测血CA125,黄体期长方案促排卵,排卵后一周（垂体降调日）再测CA125并取子宫内膜行ER、PR、HOXA-10mRNA检测。HCG日测子宫内膜厚度、形态、血流。比较临床资料及结局、症状疼痛评分。结果：实验组胚胎种植率、临床妊娠率高于对照组（P<0.05）;HCG日对照组子宫内膜厚于实验组。实验组子宫内膜A型血流比率高于对照组（P<0.05）。实验组A型子宫内膜比率高于对照组,但无明显差异（P>0.05）;IVF前两组CA125均高于参考值,但无明显差异（P>0.05）。垂体降调日复查CA125,实验组明显低于对照组,实验组治疗后低于治疗前;实验组子宫内膜ER、PR、HOXA-10 mRNA表达量高于对照组,实验组分泌期子宫内膜比率高于对照组（P<0.05）;治疗后两组各项症状疼痛评分均较治疗前改善,且实验组优于对照组（P<0.05）。结论：IVF治疗中合并卵巢子宫内膜异位囊肿用黄体酮预处理在位内膜,可以降低血CA125,有利于转变子宫内膜组织类型、减小子宫内膜厚度、增加子宫内膜血流、增加子宫内膜ER、PR、HOXA-10 mRNA表达,改善在位内膜容受性,缓解症状疼痛,提高临床妊娠率。     

子宫内膜异位症与子宫内膜息肉发病机制的相关性研究进展

子宫内膜异位症(endometriosis,EMT)和子宫内膜息肉(endometrial polyp,EP)是两类常见的良性妇科疾病,以子宫内膜组织的异常种植或增生为主要病理特征。流行病学数据显示,EMT患者的EP发生率攀升,EP患者合并EMT的风险也增加,提示二者可能存在密切关系与潜在的关联机制。尽管EMT和EP的发病机制尚未完全明确,但近年研究表明,EMT和EP的发生可能与长期高水平雌激素刺激、雌激素受体与孕激素受体表达失衡、细胞凋亡与增殖异常、细胞因子的表达、局部慢性炎症刺激、免疫系统失调、氧化应激、微生物群紊乱、代谢异常等因素有关。两者共有多种危险因素,可能参与彼此的疾病进程,从而在临床治疗上显示出消极的相互作用。本文通过对EMT和EP发病机制的相关性进行综述,为二者的基础研究和临床治疗提供更多理论依据。     

氧化应激指标与子宫内膜异位症的关系及对病情严重程度的评估价值研究

摘要 目的：分析氧化应激指标与子宫内膜异位症（以下简称内异症）的关系及对病情严重程度的评估价值。方法：选择我院自2019年5月至2022年5月接诊的126例内异症患者作为观察组,另选同期的126例卵巢良性肿瘤患者作为对照组。检测所有患者血清氧化应激指标,包括脂质过氧化特异性产物8-异前列腺素F2α（8-iso-PGF2α）、人活性氧自由基（ROS）和对氧磷酶-1（PON-1）水平,使用Pearson相关性分析氧化应激指标与美国生殖医学协会子宫内膜异位症分期（r-AFS）评分的相关性,通过多因素Logistic回归分析和AUC评价氧化应激指标对中重度囊肿粘连的预测价值。结果：观察组血清8-iso-PGF2α、ROS水平均高于对照组,PON-1水平低于对照组（P＜0.05）;在126例内异症患者中,中重度组血清8-iso-PGF2α、ROS水平均高于微轻度组,PON-1水平低于微轻度组（P＜0.05）;经Pearson相关性分析,内异症患者血清8-iso-PGF2α、ROS水平均与r-AFS评分呈正相关,PON-1水平与r-AFS评分呈负相关（P＜0.05）;经多因素Logistic回归分析,血清8-iso-PGF2α、ROS和PON-1均是内异症患者发生中重度囊肿粘连的独立预测因素（P＜0.05）;经ROC曲线分析,血清8-iso-PGF2α、ROS联合PON-1预测内异症患者发生中重度囊肿粘连的AUC为0.912。结论：内异症患者血清8-iso-PGF2α、ROS水平均明显升高,PON-1水平明显降低,三者水平与病情严重程度密切相关,联合预测中重度囊肿粘连的效能较好,值得进一步研究应用。     

补肾温阳化瘀法对子宫内膜异位症患者子宫内膜腺上皮细胞OPN与MMP-9的影响

目的:探讨补肾温阳化瘀法对子宫内膜异位症患者子宫内膜腺上皮细胞骨桥蛋白(OPN)与基质金属蛋白酶-9(MMP-9)的影响。方法:选择我院2013年4月~2016年4月收治的92例子宫内膜异位症患者,分为对照组与观察组,各46例,对照组行常规西医治疗,观察组行补肾温阳化瘀法治疗,比较两组OPN及MMP-9,雌二醇(E2)、促黄体生成素(LH)、卵泡刺激素(FSH),肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8),CD3~+、CD4~+、CD8~+、CD4~+/CD8~+,临床疗效及安全性。结果:治疗后,观察组OPN、MMP-9,TNF-α、IL-6、IL-8,CD8~+低于对照组,观察组CD3~+、CD4~+、CD4~+/CD8~+高于对照组,差异有统计学意义(P0.05)。观察组总有效率高于对照组,不良反应率低于对照组(P0.05)。结论:补肾温阳化瘀法可下调子宫内膜异位症患者子宫内膜腺上皮细胞OPN及MPP-9表达。     

米非司酮联合桂枝茯苓丸治疗子宫内膜异位症的临床效果分析

目的:分析米非司酮联合桂枝茯苓丸治疗子宫内膜异位症的临床效果。方法:106例子宫内膜异位症患者按抽签法分为对照组(n=53)与实验组(n=53),对照组采用米非司酮治疗,实验组基于对照组加以桂枝茯苓丸治疗,比较两组的临床疗效,治疗前后血清癌抗原125(CA125)、癌抗原199(CA199)、血管内皮生长因子(VEGF)、超氧化物歧化酶(SOD),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)、超敏C反应蛋白(hs-CRP)、血浆黏度、全血黏度、红细胞聚集指数的变化。结果:实验组的治疗总有效率为94.33%,显著高于对照组,差异有统计学意义(P0.05)。实验组治疗后血清CA125、CA199、VEGF、SOD、IL-6、IL-8、TNF-α、hs-CRP水平、血浆黏度、全血黏度、红细胞聚集指数均明显低于对照组(P0.05)。结论:米非司酮联合桂枝茯苓丸治疗子宫内膜异位症的临床疗效确切,可能与其抗炎、抗氧化和改善血液流变学作用有关。     

散结镇痛胶囊联合孕三烯酮对子宫内膜异位症患者性激素、子宫动脉血流动力学和血清MMPs的影响

目的：探讨孕三烯酮和散结镇痛胶囊联合治疗对子宫内膜异位症（EMT）患者性激素、子宫动脉血流动力学和血清基质金属蛋白酶（MMPs）的影响。方法：选取中国人民解放军中部战区总医院2021年1月～2022年12月期间收治的EMT患者195例,采用双色球法将患者分为对照组（孕三烯酮治疗,n=97）和观察组（散结镇痛胶囊联合孕三烯酮治疗,n=98）。对比两组疗效、性激素指标、子宫动脉血流动力学和血清MMP-2、MMP-3、MMP-9/基质金属蛋白酶抑制剂-1(TIMP-1)水平,同时观察两组不良反应发生率。结果：与对照组相比,观察组的临床总有效率更高（P<0.05）。治疗后,观察组卵泡刺激素（FSH）、黄体生成素（LH）、雌二醇（E2）低于对照组（P<0.05）。治疗后,观察组搏动指数（PI）、阻力指数（RI）低于对照组,收缩期最大流速（PSV）、舒张末期流速（EDV）高于对照组（P<0.05）。治疗后,观察组MMP-2、MMP-3、MMP-9/TIMP-1低于对照组（P<0.05）。两组不良反应发生率差异无统计学意义（P>0.05）。结论：散结镇痛胶囊联合孕三烯酮...     

子宫内膜异位症的激素治疗对卵巢纤维化和卵巢储备的影响

摘要 目的：探讨子宫内膜异位症的激素治疗对卵巢纤维化和卵巢储备的影响。方法：选取2019年9月-2021年8月西安国际医学中心医院收治的86例子宫内膜异位症患者,将其随机分为四组（A、B1、B2、C）,A组未接受任何激素治疗,B1组和B2组接受炔诺酮孕激素治疗,C组接受促性腺激素释放激素（GnRH）治疗。比较四组24个月复发率、复发期间肿瘤直径大小、抗苗勒激素（AMH）和促卵泡激素（FSH）水平以及血清转化生长因子-β1（TGF-β1）和平滑肌肌动蛋白（α-SMA）的表达。结果：与治疗前相比,A组斑点样出血以及痛经情况未发生变化（P>0.05）,B1、B2和C组斑点样出血升高,痛经情况降低（P<0.05）;治疗后,B1、B2和C组较A组斑点样出血升高、痛经情况降低,C组较B1、B2组升高（P<0.05）。与治疗期间对比,四组子宫内膜异位症复发率均发生变化（P<0.05）。在治疗期间,与A组相比,B1组、B2组和C组子宫内膜异位症复发率降低,且B1组、B2组较C组降低;在随访期间,B1组、B2组复发率低于C组（P<0.05）。与治疗期间相比,A组随访期间子宫内膜瘤直径比较无差异（P>0.05）,B1、B2和C组增大（P<0.05）。B1、B2和C组较A组子宫内膜瘤直径减小（P<0.05）,而C组较B1、B2组增大（P<0.05）。与治疗前相比,四组治疗后血清FSH水平升高,血清AMH水平降低（P<0.05）;治疗后,B1、B2和C组较A组血清FSH水平降低,AMH水平升高（P<0.05）。各组治疗后较治疗前TGF-β1和α-SMA的蛋白表达降低（P<0.05）;治疗后B1、B2和C组较A组TGF-β1和α-SMA蛋白表达水平降低（P<0.05）。结论：与GnRH相比,孕激素可能是子宫内膜异位症术后卵巢储备和纤维治疗的更好选择。     

不同病变类型子宫内膜异位症对卵巢储备功能及辅助生殖技术结果的影响

摘要 目的：探究不同病变类型子宫内膜异位症（Endometriosis,EMs）对卵巢储备功能及辅助生殖技术结果的影响。方法：选择2018年1月-2021年1月于承德医学院附属医院妇产科就诊的EMs合并不孕症患者188例作为研究对象,纳入实验组,另随机选择同期单纯男性因素不孕妇女160例作为对照。对符合临床标准的患者行IVF-ET治疗,计算其胚胎种植率、临床妊娠率、活产率,对患者血清抗苗勒氏管激素（AWH）、卵泡刺激素（FSH）、黄体生成素（LH）、窦卵泡素（AFC）水平进行检测。结果：r-AFS III期、IV期AWH水平显著低于对照组,差异具有统计学意义（t=7.00、11.86,P均<0.05）;II期、III期、IV期AFC计数显著低于对照组,差异具有统计学意义（t=4.50、8.49、9.06,P均<0.05）。r-AFS分期III期、IV期患者种植率、临床妊娠率、活产率显著低于对照组（x²=4.04、4.72、10.46、8.80、11.32、12.21,P均<0.05）。多因素logistic回归分析结果表明,r-AFS分期III期、IV期是IVF-ET不良结局的主要危险因素,具有统计学意义（P<0.05）。结论：III/IV期EMs可在一定程度上降低妇女的卵巢储备功能,同时降低了IVF-ET过程中的种植率及临床妊娠率,从而对其妊娠结局产生不良的影响。     

子宫内膜异位症的药物治疗

子宫内膜异位症(EMS)是妇科常见病,近年来发病率逐年上升,仅次于子宫肌瘤。虽然为良性疾病,却表现为恶性行为,主要特征为疼痛、不孕及性交困难,导致生活质量下降。其治疗目的在于消除病灶、缓解疼痛和解决生育问题,降低术后复发也不可忽视,因此,药物治疗尤为重要,不同的药物有不同的作用机理、副作用及用药时间。不同的患者需要根据其治疗目的、身体情况及经济状况选择不同的治疗方案。所以药物治疗应注意个体化、阶梯化和规范化。本文就近年来内异症的药物治疗做一综述。     

A Study of Changes in Uterine Leucocytes During Early Pregnancy in the Mouse-vole Interspesific Pregnancies

Mouse and vole embryos were allogeneically and xenogeneically transferred into pseudopregnant CD-1 and immunodeficient （scid） female mice, and we investigated the distribution of uterine leucocytes cells in the implantation sites on days 5,6,and 7 of pregnancy. Macrophages were evenly distributed in the endometrium on days 5 N 7. Neutrophils were rarely seen on days 5 ~ 7, but lymphoeytes were found throughout the endometrium,often in groups associated with glands or the luminal epithelium. The number of uNK cells increased markedly at the mesometrial triangle and the outer decidual area in the CD-1 uteri containing vole embryos; by contrast, scid uteri having vole embryos showed almost the same number as those having mouse embryos. Mast cells were present in large numbers at the myometrium,but rarely in the decidua in all types of pregnant uteri. Cells at the myometrium were more numerous in xenogeneic than in allogeneic transfer. Many mast cells appeared in the inner decidua where xenogeneically transferred vole embryos were dead and aborted. These results suggest the possibility that uterine leucocytes mediate various immunological events in the mouse-vole interspesific pregnancies.     

母胎界面自然杀伤细胞的研究进展

自然杀伤(natural killer,NK)细胞是母胎界面丰度最高的免疫细胞,在妊娠早期的子宫蜕膜中大量积聚.研究表明母胎界面NK细胞具有独特表型和功能,在妊娠期免疫耐受调节、子宫内膜蜕膜化、滋养细胞侵袭、子宫螺旋动脉重塑、胎盘形成和胎儿生长、发育等多方面都发挥关键作用,但是其在妊娠中的功能及其作用机制还有待深入研究...     

Interleukin-12 inhibits development of ectopic endometriotic tissues in peritoneal cavity via activation of NK cells in a murine endometriosis model

Involvement of impaired peritoneal immunosurveillance systems has been well established in the pathology of endometriosis. On the other hand, it has been observed that peritoneal administration of IL-12 suppress development of endometriotic lesions in a mouse endometriosis model. We investigated the effect of peritoneal administration of IL-12 on the peritoneal immunosurveillance system regarding NK cells in the mouse model. Treating the endometrial-tissue challenged mice with IL-12 for 5 consecutive days, from day -2 to day 2 (implantation of the endometrial tissues was done on day 0), cytotoxicity of splenic NK cells was enhanced immediately after the administration, on day 3, and development of the endometriotic lesions was reduced on day 21. In vivo NK cell depletion by administration of anti-IL-2Rβ mAb resulted in reduction of the cytotoxicity of splenic NK cells concomitant with a significant attenuation of suppressive effect of IL-12 on development of endometriotic lesions. Therefore, it was suggested that IL-12 suppresses development of endometriotic lesions via activation of NK cells, and that NK cells are involved in the primary defense for the development of endometriotic lesions.     

Studies on NK cell purification by negative selection in human peripheral blood

We have attempted to improve negative selection procedures for the large scale purification of human CD _in3 ^– CD56⁺ NK cells. In a series of experiments, purifications of NK cells from 10⁸ PBMC were performed by T cell depletion using either direct or indirect anti-CD3 labeling and the Magnetic Activated Cell Separation (MACS) procedure. Contaminating CD3⁺ cells were still present using either one of these two different T cell depletion protocols as shown by phenotyping IL-2 supplemented cell cultures on day 12. A second cycle of purification was therefore added. When MACS and Dynabeads were compared as complementary procedures to the first MACS cycle starting with 10⁸ cells, the Dynabeads method was found to be superior to the MACS with regard to the elimination of residual T cells. Starting from 10⁹ PBMC, we showed that this MACS+Dynabeads procedure gave similar satisfactory results when compared to the scaling-up of a previously established two steps procedure using Dynabeads. These two approaches (MACS+Dynabeads and 2 cycles of Dynabeads) have been also tested in a clinical setting to purify NK cells from cancer patients prior toin vitro expansion. The results indicate that the two methods are equivalent with respect to purity and recovery rate; a slight advantage in terms of feasibility was found in favor of 2 cycles of Dynabeads.     

Natural Killer Cell Receptor+ T‐Lymphocytes in Normal and Helicobacter pylori‐Infected Human Gastric Mucosa

Background: Helicobacter pylori infection is associated with development of chronic inflammation and infiltration of immune cells into the gastric mucosa. As unconventional T‐lymphocytes expressing natural killer cell receptors are considered to play central roles in the immune response against infection, a study investigating their frequencies in normal and H. pylori‐infected gastric mucosa was undertaken. Materials and Methods: Flow cytometry was used to quantify T‐cells expressing the natural killer cell markers CD161, CD56, and CD94 in freshly isolated lymphocytes from the epithelial and lamina propria layers of gastric mucosa. Thirteen H. pylori‐positive and 24 H. pylori‐negative individuals were studied. Results: CD94⁺ T‐cells were the most abundant (up to 40%) natural killer receptor‐positive T‐cell population in epithelial and lamina propria layers of H. pylori‐negative gastric mucosa. CD161⁺ T‐cells accounted for about one‐third of all T‐cells in both compartments, but the lowest proportion were of CD56⁺ T‐cells. Compared with H. pylori‐negative mucosa, in H. pylori‐infected mucosa the numbers of CD161⁺ T‐cells were significantly greater (p = .04) in the epithelium, whereas the numbers of CD56⁺ T‐cells were lower (p = .01) in the lamina propria. A minor population (< 2%) of T‐cells in both mucosal layers of H. pylori‐negative subjects were natural killer T‐cells, and whose proportions were not significantly different (p > .05) to those in H. pylori‐infected individuals. Conclusions: The predominance, heterogeneity, and distribution of natural killer cell receptor‐positive T‐cells at different locations within the gastric mucosa reflects a potential functional role during H. pylori infection and warrants further investigation.     

Population dynamics of human activated natural killer cells in culture

The growth kinetics and population dynamics of recombinent interleukin-2 (rlL-2) stimulated human natural killer (NK) cell-enriched populations were studied in vitro. The NK-enriched populations was obtained from normal peripheral blood mononuclear cells (PBMNC) by immunomagnetic bead depletion of CD3(+) and CD5(+) T cells. The growth kinetics of NK cells, T cells, monocytes, and total cells are shown. In the absence of PBMNC accessory cells, the NK-enriched population showed limited expansion. In the presence of PBMNC accessory cells, the NK-enriched population expanded threefold more than in the absence of accessory cells due to increased NK cell growth rate and increased duration of exponential growth. Using a Transwell system, which separates two cell population by a polycarbonate membrane, the accessory cells were shown to act on the NK-enriched population via a diffusible factor. Accessory cell conditioned media was able to replace the accessory cell population to stimulate NK cell expansion. A monocyte-enriched population prepared by sheep red blood cell rosetting of T cells was extensively phenotyped and compared with the NK-enriched populations. Although the final cultured cells were phenotypically homogeneous for CD56(+)/CD3(-) NK cells, the initial NK precusor populations appear to be different. Namely, the NK cell precursors in the monocyte-enriched population were predominantly CD56(+)/CD2(-). Kinetic equations were formulated for this culture system and the effects of major culture variables are investigated.     

Successful adoptive immunotherapy with OK432-inducible activated natural killer cells in tumor-bearing mice

We had demonstrated that the NK cell mediated cytotoxicity of murine spleen cells could be augmented byin vivo priming and subsequentin vitro challenge with a streptococcal preparation OK432, and the cell surface phenotype of induced killer cells was Thy-1⁺, asialo GM1⁺, suggesting that the activated cells were of NK lineage (OK-NK cell). We had also clarified that IL-2 played a major role in inducing the OK-NK cells via the production of IFN-. In this study, we examined the effect of adoptive transfer of OK-NK cells on syngeneic tumors in mice. Mice were implanted with SP2 myeloma cells intraperitoneally (i.p.), or C26 colon adenocarcinoma cells subcutaneously to make the models of peritonitis carcinomatosa or solid tumor, and the OK-NK cells were transferred i.p. or intratumorally, adoptively. By the adoptive transfer of OK-NK cells, 92% of mice bearing SP2-tumor had be cured. The tumor growth of C26-solid tumor was inhibited, and the survival rate of mice bearing C26-tumor was significantly increased. The intratumoral remnants of¹²⁵I-labelled OK-NK cells were 61, 27 and 8% at 4, 12 and 36h after intratumoral transfer, respectively. By multiple transfer of OK-NK cells, the antitumor effect was more effectively augmented than that of a single transfer. Results in this study suggested that OK-NK cells could be useful for the therapy of cancer patients.     

Mechanisms of lymphocyte-mediated lysis

Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells use multiple mechanisms to destroy their target cells. Pore formation resulting in osmotic lysis of the target is one mechanism; the pore-forming protein (perforin) responsible for this activity has been purified. Antigenically and functionally it resembles proteins of the membrane attack complex of complement. The other known mediators of cytotoxicity appear to be closely interrelated. Tumor necrosis factor (TNF), lymphotoxin (LT), and leukalexin are the three members of this group that have been purified, although their mechanisms of action are still unknown. CTLs fragment the DNA of target cells, as do TNF, LT, and leukalexin; this may be one of the mechanisms of action of these mediators. CTLs and NK cells do not self lyse. The basis of this phenomenon is unclear, although recent advances have shed some light on the problem.