AbstractBackgroundTo explore the clinical application value of pre‐conception expanded carrier screening (PECS) in the Chinese Han ethnicity population of childbearing age.MethodsThe results of genetic testing of infertile parents who underwent PECS in the Reproductive Medicine Center of the Second Affiliated Hospital of Zhengzhou University, China, from September 2019 to December 2021, were retrospectively analyzed. The carrier rate of single gene disease, the detection rate of high‐risk parents, and the clinical outcome of high‐risk parents were statistically analyzed.ResultsA total of 1372 Chinese Han ethnicity patients underwent PECS, among which 458 patients underwent the extended 108‐gene test, their overall carrier rate was 31.7%, and the detection rate of high‐risk parents was 0.3%. The highest carrier rates were SLC22A (2.4%), ATP7B (2.4%), MMACHC (2.2%), PAH (1.8%), GALC (1.8%), MLC1 (1.3%), UNC13D (1.1%), CAPN3 (1.1%), and PKHD1 (1.1%). There were 488 women with fragile X syndrome—FMR1 gene detection, and 6 patients (1.2%) had FMR1 gene mutation. A total of 426 patients were screened for spinal muscular atrophy—SMN1, and the carrier rate was 3.5%, and the detection rate of parents' co‐carrier was 0.5%.ConclusionMonogenic recessive hereditary diseases had a high carrier rate in the population. Pre‐pregnancy screening could provide good prenatal and postnatal care guidance for patients and preimplantation genetic testing for monogenic/single gene disorders (PGT‐M) and prenatal diagnosis could provide more precise reproductive choices for high‐risk parents.

Accumulating evidence has demonstrated that high-risk human papillomaviruses (HR-HPVs) are involved in the etiology of a subset of oropharyngeal squamous cell carcinoma (OPSCC). In this regard, the International Agency for Research on Cancer (IARC) has recommended direct molecular HPV testing. So far, there is no agreement on the most appropriate method for HPV detection on OPSCC formalin-fixed paraffin-embedded (FFPE) materials. In this study, we aimed to evaluate the performance of the high-sensitive SureX HPV assay in OPSCC FFPE tissues compared with LiPA-25 and p16ink4a immunostaining. A retrospective series of FFPE primary OPSCC cases were diagnosed between 2008 and 2019 and provided by the Henan Cancer Hospital, China. The level of agreement of two assays was determined using Cohen's Kappa (kappa) statistics. A total of 230 FFPE OPSCC samples from tumor resections (n = 160) and diagnostic biopsies (n = 70) were detected. Sixty-six (28.7%) and 70 (30.4%) samples were identified as HPV-DNA-positive by LiPA-25 and SureX, respectively, of which HPV16 was largely the most common type (95.5% vs 94.3%). We found a perfect concordance between LiPA-25 and SureX for HPV-DNA status (kappa = 0.906, 95% CI: 0.875-0.937) and for HPV16 (kappa = 0.925, 95% CI: 0.897-0.953). In addition, SureX and p16ink4a immunostaining had a perfect concordance (kappa = 0.917, 95% CI: 0.888-0.946). Moreover, the HPV-driven fraction, based on double positivity for HPV-DNA and p16ink4a, was similar between SureX (63 of 230, 27.4%) and LiPA-25 (60 of 230, 26.1%). Similar results were found in samples from resections and biopsies. SureX and LiPA-25 are comparable. SureX could be used for routine HPV-DNA detection and genotyping on archival OPSCC FFPE tissues.

目的 分析宫颈剪切波弹性成像(SWE)预测体外受精-胚胎移植(IVF-ET)术后双胎妊娠早产的价值.方法 以2019年9月至2021年4月217例郑州大学第二附属医院IVF-ET术后双胎妊娠孕妇作为研究对象,在孕20～23周时使用经阴道超声分别测量宫颈内、外口,前、后壁的SWE杨氏模量值及宫颈长度(CL),门诊或电话随访妊娠结局.结果 根据分娩孕周,将研究对象分为自发性早产(sPTD)组(58例)和足月产组(159例);sPTD组与足月产组相比,宫颈SWE杨氏模量值较小,宫颈内口前壁(AI):Z=-9.099,P＜0.01;内 口后壁(PI):Z=-8.215,P＜0.01;外口前壁(AE):Z=-3.532,P＜0.01;外 口后壁(PE):Z=-6.426,P＜0.01);CL较短(Z=-6.850,P＜0.01);宫颈4个区域的杨氏模量值彼此相关,宫颈内口较外口硬(AI/AE:Z=-12.219,P＜0.01;PI/PE:Z=-12.645,P＜0.01),AI较PI软(AI/PI:Z=-8.376,P＜0.01);宫颈AI 的 SWE 杨氏模量值预测IVF-ET术后双胎妊娠孕妇早产的受试者工作特征(ROC)曲线下面积(AUC)值最大(0.904＞0.865＞0.657＞0.785),宫颈AI的SWE杨氏模量值相比CL预测效能更高(0.904＞0.804).结论 宫颈SWE可有效预测IVF-ET术后双胎早产,预测效能优于CL.

目的 评价取卵后使用促性腺激素释放激素拮抗剂(GnRH-ant)防治中/重度卵巢过度刺激综合征(OHSS)的应用价值.方法 收集2019年10月至2022年10月在郑州大学第二附属医院生殖中心接受拮抗剂方案助孕因OHSS高风险行全胚冷冻的160例患者作为研究对象,根据取卵术后使用的药物不同分为GnRH-ant组(n=80)与对照组(n=80);对照组采用常规治疗及取卵术后第2天开始给予低分子肝素钙治疗5 d,而GnRH-ant组在对照组治疗的基础上于取卵术后当日开始给予GnRH-ant治疗3～7 d.比较两组患者的一般资料、促排卵情况、OHSS相关临床和实验室指标及临床结局,并采用Spearman相关性分析探讨GnRH-ant组患者各临床指标与中/重度OHSS的关系.结果 GnRH-ant组的获卵数、2PN胚胎数及冷冻胚胎数均显著高于对照组(P＜0.05);GnRH-ant组取卵后提前来月经的患者比例显著高于对照组(P＜0.05);GnRH-ant组穿刺放腹水比例、中/重度OHSS发生率及取卵后2～5 d雌二醇(E2)、白细胞计数(WBC)、血红蛋白(Hb)、红细胞比容(HCT)、血管内皮生长因子(VEGF)、血浆纤维蛋白原(FIB)均显著低于对照组(P＜0.05).Spearman相关性分析结果显示,GnRH-ant组患者的中/重度OHSS发生与取卵后GnRH-ant总剂量呈负相关(r=-0.224,P＜0.05),与获卵数呈正相关(r=0.252,P＜0.05).结论 取卵后使用GnRH-ant可以加速黄体溶解并显著降低OHSS高危患者E2及VEGF水平,降低中/重度OHSS发生风险,并能改善患者的凝血功能,降低血栓风险.

目的 探讨孕前扩展性携带者筛查(preconception expanded carrier screening,PECS)在中国汉族育龄人群中的临床应用价值.方法 回顾性研究2019年9月至2022年5月期间于郑州大学第二附属医院生殖医学中心采用序贯筛查模式进行PECS的不孕不育夫妇的基因检测结果,对单基因病致病基因携带率、高危夫妇携带率及高危夫妇的临床结局进行统计和分析.结果 共有1 565例患者接受PECS,均为汉族人群,其中接受扩展型108种单基因病检测的女性患者420例,男性患者84例,目标基因总体携带率为30.75%(129/420).检出1对高危夫妇,携带率为1.19%(1/84),检测基因中携带率较高的分别是MMACHC[2.58%(13/504)]、ATP7B[(2.38%(12/504)]、SLC22A5[2.18%(11/504)]、GALC[1.79%(9/504)]、PAH[1.79%(9/504)]、MLC1[1.19%(6/504)],余下均不足1%.接受脆性X综合征FMR1基因检测的患者共555例,FMR1基因突变5例,占0.90%,对全突变患者直系亲属进行检测,其母亲为前突变携带者(CGG重复数为105).接受脊髓型肌萎缩症SMN1基因携带者筛查的患者共502例,女性阳性携带者14例,男性阳性携带者2例,总体携带率为3.19%.结论 单基因隐性遗传病在人群中携带率较高,孕前进行筛查可以为患者提供优生优育指导,选择胚胎植入前单基因遗传学检测(preimplantation genetic testing for monogenic/single gene disorders,PGT-M)和产前诊断,可避免患儿的出生.

[目的]探讨基线细胞学正常妇女在3年随访过程中感染高危型人乳头瘤病毒(HR-HPV)及发生宫颈病变的情况.[方法]选择2017年4月至5月在河南省济源市宫颈癌筛查中细胞学结果正常的3 555名妇女为研究对象.对所有研究对象随访3年,HR-HPV阳性者每年随访1次,HR-HPV阴性者第3年随访1次.随访中以病理诊断结果为宫颈上皮内瘤变2级及以上(CIN2+)为终点,分析HPV感染变化和CIN2+的发病风险.[结果](1)HR-HPV阴性者:共2 455名基线细胞学正常且HR-HPV阴性妇女在第3年成功随访,HR-HPV新发阳性率为13.08％(321/2 455),其中HPV 16、18、33、52和58型别的新发阳性率分别为 2.00％、0.94％、0.90％、3.50％、1.71％;年龄＜45 岁者 HR-HPV、HPV 16、HPV 52 新发阳性率均低于≥45岁者(10.7％vs 14.6％、0.9％vs2.7％、2.2％vs 4.3％),差异均具有统计学意义(P均＜0.05).细胞学结果为意义不明的不典型鳞状细胞及以上者63例,8例被诊断为CIN1,3例被诊断CIN2,病变进展率为0.45％.(2)HR-HPV阳性者:共573名基线细胞学正常而HR-HPV阳性妇女需要随访,3次随访时 HR-HPV 转阴率分别为 29.68％、39.06％、46.80％,CIN2+检出率分别为 2.59％、2.58％、2.43％,3年CIN2+累计发生率为7.53％.年龄＜45岁者3次随访HR-HPV转阴率均高于≥45岁者(35.5％vs 26.8％、51.0％vs33.1％、58.6％vs 40.5％),差异均有统计学意义(P均＜0.05).[结论]宫颈癌筛查人群中细胞学正常且HR-HPV阴性妇女,其3年后随访时HR-HPV新发阳性率和CIN2+的发生风险均较低.细胞学正常而HR-HPV阳性妇女中,≥45岁者不仅清除既往HR-HPV感染的能力减弱,且更易出现新发感染或多种型别共感染现象,发生CIN2+的风险也较高.因此,可以适当延长基线细胞学正常且HR-HPV阴性妇女的随访时间间隔,对围绝经期女性人群应加强随访监测.

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OBJECTIVE:To analyze the effect of factors relevant to blastocyst transfer on the pregnancy outcome of in vitro fertilization-embryo transfer (IVF-ET). METHODS:The clinical data of 790 pregnant women who underwent IVF-ET in our hospital from July 2015 to July 2020 were retrospectively analyzed. The pregnancy outcome of blastocysts transferred on day 5 (D5, n=705) and those transferred on day 6 (D6, n=85) were compared. According to the pregnancy outcome, the cases were divided into a live birth group ( n=322) and a non-live birth group ( n=468), and multivariate logistic regression was conducted to study the effect of factors relevant to blastocyst transfer on the live birth outcome of IVF-ET. RESULTS:In the D5 group, the biochemical pregnancy rate, clinical pregnancy rate and live birth rate of blastocyst transfer were 69.93%, 64.96%, and 41.84%, respectively, which were significantly higher than those of the D6 group at 50.59%, 45.88%, and 30.59%, respectively. The difference was statistically significant ( P<0.05). There was no statistically significant difference in the miscarriage rate between the D5 group and the D6 group ( P>0.05). Multivariate logistic analysis revealed that age>35 years, years of infertility>5 years, endometrium thickness<9 mm on the day of blastocyst transfer, trophoblast cell rating of C, blastocyst transfer performed on D6, and multiparity were all risk factors for non-live birth outcome of IVF-ET ( P<0.05). CONCLUSION:The adverse pregnancy outcomes of IVF-ET were found to be associated with age, duration of infertility, endometrial thickness on the day of to blastocyst transfer, trophoblast cell rating, and blastocyst transfer performed after how many days of embryo development, and multiparity, which should be closely monitored, and effective measures should be adopted accordingly to prevent adverse outcomes of pregnancy.

目的 观察体外受精-胚胎移植(in vitro fertilization-embryo transfer,IVF-ET)反复种植失败患者宫腔镜检查情况及子宫内膜CD138表达情况,探讨子宫内膜CD138阳性表达联合宫腔镜检查对IVF-ET反复种植失败患者合并慢性子宫内膜炎的诊断价值.方法 行IVF-ET的患者147例,其中反复种植失败患者81例为失败组,一次移植成功患者66例为成功组,2组患者均行宫腔镜检查及子宫内膜组织病理检查,观察慢性子宫内膜炎发生情况;2组均行子宫内膜组织免疫组织化学检查,观察子宫内膜组织CD138阳性表达情况.比较不同临床病理特征的IVF-ET反复种植失败患者子宫内膜组织CD138阳性表达率;绘制ROC曲线,评估子宫内膜组织CD138阳性表达、宫腔镜检查对IVF-ET反复种植失败患者合并慢性子宫内膜炎的诊断效能.结果 失败组患者宫腔镜检查慢性子宫内膜炎检出率(60.49％)、子宫内膜组织病理检查慢性子宫内膜炎检出率(39.51％)、子宫内膜组织CD138阳性表达率(60.49％)均高于成功组(24.24％、10.61％、37.88％) (P＜0.05).有经期延长、慢性子宫内膜炎、输卵管阻塞、移植次数＞3次的IVF-ET反复种植失败患者子宫内膜组织CD138阳性表达率(88.24％、92.31％、66.18％、87.50％)分别高于无经期延长、无子宫内膜炎、无输卵管阻塞、移植次数2～3次者(53.13％、3.45％、30.77％、53.85％)(P＜0.05),不同年龄、体质量指数、月经周期、不孕时间及有无孕产史、既往流产史、宫颈衣原体感染、阴道炎史、宫颈支原体感染、盆腔炎的IVF-ET反复种植失败患者子宫内膜组织CD138阳性表达率比较差异均无统计学意义(P＞0.05).子宫内膜组织CD138阳性表达和宫腔镜检查诊断IVF-ET反复种植失败患者合并慢性子宫内膜炎的AUC分别为0.620(95％CI:0.496～0.744,P=0.069)、0.568(95％CI:0.441～0.696,P=0.301),灵敏度分别为75.0％、68.75％,特异度分别为48.98％、44.90％;二者联合诊断IVF-ET反复种植失败患者合并慢性子宫内膜炎的AUC[0.785(95％CI:0.685～0.886,P＜0.001)]大于单独检测(Z=3.823,P＜0.001;Z=4.528,P＜0.001),灵敏度为93.75％,特异度为63.27％.结论 有经期延长、慢性子宫内膜炎、输卵管阻塞、移植次数＞3次的IVF-ET反复种植失败患者子宫内膜组织CD138阳性表达率增高;子宫内膜组织CD138阳性表达联合宫腔镜检查可提高对IVF-ET反复种植失败患者合并慢性子宫内膜炎诊断率.

Introduction: Successful pregnancy in humans requires adequate maternal-fetal immune tolerance. During regulatory T (Treg) cells play a key role. Sphingosine-1-phosphate (S1P) and S1P receptor (S1PR) signaling represses Treg cell differentiation, but whether this relates to the process of recurrent pregnancy loss is still unclear. Methods: Treg cells in the placenta were examined using flow cytometry. The expression of sphingosine kinase-1 and -2(SPHK1 and SPHK2), two key kinases controlling S1P production, was detected in placenta samples from 36 patients with recurrent pregnancy loss (RPL) and 40 control participants using immunoblotting. The level of sphingosine-1-phosphate receptor-1 (S1PR1) in placental T cells was examined using RT-qPCR and immunoblotting. Cell surface S1PR1 levels were detected using flow cytometry. The interactions between miRNAs and S1PR1 mRNA were predicted using bioinformatics tools and were confirmed by dual luciferase assay and immunoblotting. Results: RPL patients had fewer Treg cells (p = 0.034) in the placenta, especially TIM3+ Treg cells (p = 0.0076). S1PR1 protein levels were significantly increased in placental T cells of patients with RPL (p = 0.0065). MiR-33a, miR-33b, and miR-181a were reduced in the placenta from patients with RPL, which were identified to repress S1PR1 expression by targeting the 3'UTR. Knockdown of miR-33a, miR-33b and miR-181a in human naive T cells inhibits Treg cell differentiation by upregulating S1PR1 in vitro. Discussion: This study, for the first time, successfully constructed the correlation between dysregulated miRNAs in placenta and RPL, which partially unveiled the etiology of RPL and provided a therapeutic potential for RPL treatment.

目的:探讨多囊卵巢综合征(PCOS)患者在卵泡期长效长方案助孕治疗中,血清抗米勒管激素水平(AMH)水平和促性腺激素(Gn)剂量对妊娠结局的预测价值.方法:选取2019年3月至2022年3月在郑州大学第二附属医院生殖医学部就诊接受体外受精-胚胎移植(IVF-ET)助孕治疗行卵泡期长效长方案的PCOS患者420例,根据血清AMH水平分为3组:低AMH水平组(血清AMH<5.01 μg/L,n=105)、中AMH水平组(血清AMH 5.01~9.09 μg/L,n=210)、高AMH水平组(血清AMH>9.09 μg/L,n=105),比较3组的妊娠结局.采用Logistic回归分析不同AMH水平组临床妊娠的影响因素.采用ROC曲线分析低、中AMH水平组Gn剂量对临床妊娠的预测价值.结果:低AMH水平组Gn剂量高于中、高AMH水平组;高AMH水平组HCG日E2水平、获卵数及卵巢过度刺激综合征高风险周期取消率高于低、中水平组;高AMH水平组新鲜周期移植率低于低、中水平组(P<0.05).Lo-gistic回归结果显示低、中AMH水平组Gn剂量是PCOS患者临床妊娠的影响因素.ROC曲线显示在低AMH水平组,Gn剂量对临床妊娠影响的AUC为0.707(95%CI为0.604~0.810),Gn剂量最佳截断值为2 789 IU,敏感度为0.828,特异度为0.605;在中AMH水平组,Gn剂量对临床妊娠影响的AUC为0.616(95%CI为0.540~0.692),Gn剂量最佳截断值为2 220 IU,敏感度为0.692,特异度为0.552.结论:低、中AMH水平组Gn剂量对妊娠结局有一定的预测价值.

目的 探讨基于杂交捕获原理的DH2检测技术在未明确意义的不典型鳞状细胞(Atypical squamous cells of undetermined significance,ASC-US)人群中的分流应用效果.方法 本研究于2016年10月—2018年10月在河南省新密市招募21～64岁普通女性参加研究.所有女性在签署知情同意书后完成妇科检查及宫颈脱落细胞学采集,并采用DH2进行高危HPV检测.同时,所有研究对象均进行阴道镜检查,并在必要时进行组织活检.阴道镜检查结果及病理诊断结果作为DH2的应用效果评价的金标准.结果 研究共入组302例女性,中位年龄为52岁.DH2检测结果为阳性者49例(16.2％)、3例(1％)被确诊为宫颈鳞状上皮内瘤样病变Ⅱ级(Cervical intraepithelial neoplasia grade 2,CIN2)、14例(4.6％)被确诊为宫颈鳞状上皮内瘤样病变Ⅲ级及以上(Cervical intraepithelial neoplasia grade 3 or worse,CIN3+)病变.以CIN2+为临床终点时,DH2的灵敏度、特异度、阳性预测值和阴性预测值分别为82.4％、87.7％、28.6％及98.8％;以CIN3+为临床终点时,DH2的灵敏度、特异度、阳性预测值和阴性预测值分别为85.7％、87.2％、24.5％、99.2％.结论 DH2在ASC-US人群中检出CIN2+病变、CIN3+病变的灵敏度和特异度均较高,是ASC-US人群分流的有效方法,有望与细胞学筛查联合,减轻宫颈癌的健康危害.

目的:为了探讨盆腹腔上皮样炎性肌纤维母细胞肉瘤的临床特点、诊断、治疗和预后,对其病理学特点进行研究分析.方法:选取2018年06月我院接诊且病理科病理诊断为盆腹腔上皮样炎性肌纤维母细胞肉瘤的1例患者作为研究对象,分别通过巨检、镜检、免疫表型以及免疫组织化学的方法对病理标本进行分析,并通过查阅相关文献,复习相关文献,对盆腹腔上皮样炎性肌纤维母细胞肉瘤的临床特点做进一步的研究.结果:镜下见肿瘤细胞排列紊乱,连成片状,大小不一,形态多样.主要组成为上皮样细胞,肿瘤细胞形状呈圆形、短梭形、多边形、椭圆形及不规则形.细胞排列较为松散,弥散分布.肿瘤细胞核仁较大,镜下可见核分裂象和瘤巨细胞;间质中见明显的大量炎症细胞浸润,炎性浸润以中性粒细胞为主,伴有少量浆细胞、淋巴细胞及嗜酸性粒细胞;胞质丰富,肿瘤细胞有明显水肿和黏液样变性.部分癌变区域排列较为密集,细胞形态不清.肿瘤细胞免疫组化结果vimentin、desmin、核膜ALK、CD30弥漫性表达强阳性,而ALK特异性的在细胞核膜阳性表达.部分肿瘤细胞EMA、INI-1、AAT、SMA、CK部分、p53部分阳性.FISH检测结果显示肿瘤细胞多有单一红色信号及红绿分离信号,多为阳性.结论:盆腹腔上皮样炎性肌纤维母细胞肉瘤发病较为罕见,是高度恶性肿瘤,预后较差.但是其病理学和免疫组化特点较为突出,根据病理学结果更有利于临床诊断.

Objective To evaluate the clinical performance and utility for risk stratification of DH3 HPV assay in women (≥30 years) with NILM cytology. Methods A prospective cohort was established in Central China between November 8 to December 14, 2016 which consisted of 2180 women aging 30-64 years with NILM cytology. At baseline, all women were screened using DH3 HPV assay. HPV 16/18 positive women would be assigned to colposcopy and biopsied if necessary. Then, hr-HPV positive women without CIN2+ lesions would be followed up by cytology every 12 months for two years. In the 3rd year of follow up, all women that were not biopsy proven CIN2+ would be called back and screened by cytology again. In follow-up period, women with ASC-US and above were referred to colposcopy and biopsied if clinically indicated. CIN2+ was the primary endpoint in analysis. The clinical performance and utility for risk stratification of DH3 HPV assay were assessed by SPSS 22.0 and SAS 9.4. Results Of 2180 qualified women, the prevalence of hr-HPV was 8.5% (185/2180), 45(2.1%) were HPV 16/18 positive. The clinical performance for HPV16/18 was 91.7% for sensitivity, 98.4% for specificity, respectively against CIN2+ detection at baseline. In four years of study, the corresponding rates of HPV 16/18 were 51.5% and 98.7%, respectively. The cumulative absolute risk for the development of CIN2+ was as high as 37.8% for HPV 16/18 positive women, followed by hr-HPV positive (14.6%), other hr-HPV positive (11.0%) and HPV negative (0.3%) in three years. The relative risk was 125.6 and 3.4 for HPV 16/18 positive group when compared with HPV negative and other hr-HPV positive group, respectively. Conclusions DH3 HPV assay demonstrated excellent clinical performance against CIN2+ detection in cervical cancer screening and utility of risk stratification by genotyping to promote scientific management of women with NILM cytology.

Background To investigate whether micro ribonucleic acid-664a-3p (miR-664a-3p) targeting BCL2A1 affects the proliferation and apoptosis of ovarian granulosa cells. Methods Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-664a-3p in granulosa cells, granular tumor cell lines (KGN), and normal ovarian epithelial cell lines (IOSE80) in the polycystic ovary syndrome (PCOS) group and the control group. After overexpressing miR-664a-3p or inhibiting its expression in KGN cells, qRT-PCR and Western blotting were used to detect the messenger RNA (mRNA) and protein levels of related genes. At the same time, a cell counting kit-8 (CCK-8) and flow cytometer were used to detect cell proliferation and apoptosis. The TargetScan website was used to predict the potential binding sites of miR-664a-3p and B-cell lymphoma 2-related protein A1 (BCL2A1), which was further verified by qRT-PCR, Western blotting, and the luciferase reporter gene method. Results The expression of miR-664a-3p was significantly decreased in both PCOS tissues and KGN cells (both P<0.05), and the overexpression of miR-664a-3p inhibited the proliferation of KGN cells and induced their apoptosis. Moreover, our results confirmed that miR-664a-3p directly targets BCL2A1 (P<0.05), and the inhibitory effect of miR-664a-3p on KGN cells was reversed by BCL2A1 overexpression (both P<0.05). The up-regulation of BCL2A1 promotes cell proliferation and reduces cell apoptosis by the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway (both P<0.05). Conclusions The up-regulation of miR-664a-3p inhibits the proliferation of KGN cells and increases apoptosis by down-regulating the expression of BCL2A1 and blocking the MAPK/ERK signaling pathway.

Objective: To evaluate the performance of high risk human papilloma virus (HR-HPV) E6/E7 mRNA in triaging women with atypical squamous cells of undetermined signification (ASCUS). Methods: The ASCUS cohort determined by liquid-based cytology test in the cervical cancer screening queue in Luoshan County, Xinyang City, Henan Province 2017 were selected. The population underwent colposcopy biopsy and pathological tests, combined with HPV16 or 18 (HPV16/18), HR-HPV DNA and HPV E6/E7 mRNA test. By using the pathological result as the gold standard, the sensitivity, specificity, positive predictor (PPV), negative prediction (NPV), referral rate and 95% confident interval (CI) of HPV E6/E7 mRNA, HR-HPV DNA, HPV16/18 were calculated, respectively. Results: The average age of 312 ASCUS women was 52.6±7.3 years old. Among the 290 women diagnosed as normal by pathology, 64 (22.1%) were HPV E6/E7 mRNA positive, 86 (29.7%) were HR-HPV DNA positive, and 19 (6.6%) were HPV16/18 positive. All of the cervical intraepithelial neoplasia (CIN) cases determined by pathology were both HPV E6/E7 mRNA and HR-HPV DNA positive. The sensitivity, specificity, PPV, NPV and referral rate of HPV E6/E7 mRNA for predicting CIN2+ lesion in women with ASCUS were 100.0% (95%CI: 72.3, 100.0), 77.8% (95%CI: 72.8, 82.1), 13.0% (95%CI: 7.2, 22.3), 100.0% (95%CI: 98.4, 100.0) and 24.7%. Compared with HPV E6/E7 mRNA, the sensitivity of HR-HPV DNA was similar with HPV E6/E7 mRNA, but with a lower specificity [70.2% (95%CI: 64.8, 75.1), P<0.05], a higher referral rate (32.1%, P<0.05); while HPV 16/18 had a high specificity (93.4%, 95%CI: 90.0, 95.7) and a low sensitivity (30.0%, 95%CI: 10.8, 60.3). Based on the age stratification by age 45, the sensitivity of HPV E6/E7 mRNA in both age groups was 100.0%. The specificity of HPV E6/E7 mRNA in group of ≥45 years was a little higher than that in group of <45 years [79.0% (95%CI: 73.7, 83.5) versus 68.3% (95% CI: 53.0, 80.4)], but the difference was not statistically significant (P>0.05). Conclusions: The ASCUS woman triaging effect of HPV E6/E7 mRNA detection is better than those of HR-HPV and HPV16/18 under certain conditions. The application of HPV E6/E7 mRNA detection to triage ASCUS population can avoid unnecessary colposcopy referral and reduce the missed diagnosis of cervical lesions.

[目的]探讨p16/Ki-67免疫细胞双染法对宫颈细胞学为未明确意义的非典型鳞状上皮细胞(ASCUS)人群的分流效果.[方法]以2016年4月至12月在郑州大学第二附属医院妇科门诊就诊且被诊断为ASCUS的135例妇女为研究对象,收集其宫颈脱落细胞标本,进行14种高危型HPV DNA及p16/Ki-67蛋白检测,所有妇女均进行阴道镜活检和病理学检查.以组织病理学诊断为金标准,分别计算p16/Ki-67双染、高危型HPV (HR-HPV)和HPV16/18检测的敏感性、特异性、阳性预测值(PPV)、阴性预测值(NPV)、转诊率及其95％CI.[结果]135例ASCUS妇女平均年龄为(46.48±10.19)岁(23～64岁),其中诊断为宫颈上皮内瘤变(CIN)1级者7例,诊断为CIN2级及以上(CIN2+)者22例.随异常病理结果的严重性增加,p16/Ki-67双染、HR-HPV和HPV16/18检出阳性率均升高(P＜0.001).以CIN2+作为疾病终点指标时,p16/Ki-67双染对ASCUS人群分流的敏感性、特异性、PPV、NPV和转诊率分别为86.4％(95％CI:66.7％～95.3％)、85.8％ (95％ CI:78.2％ ～91.1％)、54.3％ (95％ CI:38.2％～69.5％)、97.0％ (95％ CI:91.6％～99.0％)和25.9％,与之相比,HR-HPV检测敏感性稍高[95.5％(95％CI:78.2％～99.2％)],但特异性较低[68.1％ (95％ CI:59.1％～76.0％)],转诊率较高(42.2％),且差异均有统计学意义(P＜0.05).与p16/Ki-67双染法相比,HPV16/18的特异性较高[92.9％(95％CI:86.7％～96.4％)],但敏感性很低[59.1％(95％CI:38.7％～76.7％)].按照45岁进行年龄分层后,p16/Ki-67双染在≥45岁组ASCUS人群中分流效果要更好,敏感性为81.8％(95％CI.52.3％～94.9％),特异性为95.5％(95％CI:87.5％～98.4％).[结论]P16/Ki-67双染检测在保持高敏感性的同时,有更高的特异性,因此对ASCUS人群的分流效果优于HR-HPV和HPV16/18.P16/Ki-67双染检测具有简便、客观、高效、易于重复的特点,可为ASCUS人群提供一种新的分流方法.

患者女童,3岁,1年前无明显诱因左前臂突然出现一肿物,约"黄豆"大小,无明显压痛及叩击痛,后肿物缓慢增大.于当地医院就诊行局部肿物切除术,术后病理不详.2个月余前,原手术部位再次出现肿物,当地医院MRI示:左前臂前侧皮下软组织内异常信号,考虑软组织肿瘤,随后来我院就诊.

目的 探讨经皮雌二醇凝胶联合口服芬吗通在重度宫腔粘连术后治疗中的应用.方法 选择2019年5月至2020年10月在我院生殖医学部经宫腔镜确诊为重度宫腔粘连并实施宫腔粘连分离术的不孕患者60例为研究对象,按照随机数字表及1:1匹配分为研究组(30例,口服芬吗通联合经皮雌二醇凝胶给药)和对照组(30例,单纯口服芬吗通).比较两组患者给药2个人工周期后血清E2水平、宫腔形态恢复情况、内膜厚度、不良反应发生情况及满意度评分.结果 两组患者治疗前血清E2水平及子宫内膜厚度比较均无显著性差异(P>0.05);两组患者治疗后血清E2水平及子宫内膜厚度均显著高于治疗前(P=0.000).两组患者间治疗后血清E2水平、内膜厚度比较均无显著性差异(P>0.05);治疗后两组患者的月经量恢复情况、宫腔形态恢复情况比较亦无显著性差异(P>0.05);研究组患者治疗过程中不良反应发生率显著低于对照组(P<0.05),满意度评分则显著高于对照组(P<0.05).两组患者满意度评分与不良反应发生率均存在显著负相关关系(P<0.05).结论 经皮雌二醇凝胶联合口服芬吗通用于重度宫腔粘连术后治疗临床效果满意,可作为宫腔粘连术后应用雌激素的给药策略之一.