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2023 2

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REC114 1

ZNF438 1

不孕症 1

不育夫妇 1

不良孕产 1

全外显子测序 1

多囊卵巢综合征 1

市级鉴定 1

并发症 1

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排卵反应 1

染色体断裂率 1

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一项关于药物和补充剂对改善男性不育症患者的自然妊娠和精液参数影响的系统综述和网状荟萃分析 Article

李建, 吴奇, Ernest Hung Yu Ng, Ben Willem J. Mol, 吴效科, Chi Chiu Wang

《工程（英文）》 2022年第16卷第9期页码 198-209 doi: 10.1016/j.eng.2021.07.009

摘要：

本研究采用网状荟萃分析对药物和补充剂治疗特发性男性不育症的疗效进行比较，以获得最佳治疗方法。对Medline、EMBASE、OVID和CNKI等数据库中发表于1990年1月至2021年6月的文献进行检索，检索关键词包括“男性不育”“药物疗法”“补充/营养疗法”及其相关术语等。将研究药物[主要包括促卵泡激素（FSH）、雄激素、克罗米芬/他莫昔芬（SERM）]或补充剂[主要是锌、硒、维生素C/E、卡尼丁、辅酶Q₁₀（CoQ₁₀）或联合治疗]治疗特发性不育男性的随机对照试验（RCT）纳入meta分析。按PRISMA声明中的报告规范提取数据，并使用偏倚风险工具和适用于网状meta分析的GRADE系统评估证据质量。研究的主要结局是活产率和自然妊娠率（SPR），次要结局是精子参数（包括精子浓度、前向运动百分比和形态）和不良反应。65项RCT被纳入分析，共包括7541名精子参数异常但激素水平正常的育龄男性。36项研究报道SPR，但仅三项研究报道活产率。纳入研究的质量评价为中、高级。与安慰剂或未治疗相比，卡尼汀联合维生素治疗显著增加SPR（RR = 3.7, 95% CI为1.6 ~ 8.5），脂肪酸补充剂显著增加精子浓度（MD = 12.5 × 10⁶ mL^–1, 95% CI为3.1 × 10⁶ ~ 22.0 × 10⁶）。SERM联合辅酶Q₁₀显著提升前向活力精子（MD = 11.0%, 95% CI为0.1% ~ 21.9%）和正常形态精子（MD = 11.0%, 95% CI为4.6% ~ 17.4%）。对改善SPR和精子浓度的最佳治疗方案分别是卡尼汀联合维生素和脂肪酸补充剂，即便排除具有高偏倚风险的研究，结果仍保持一致。对于少弱精子症男性，与安慰剂或未治疗相比，FSH（RR = 4.9, 95% CI为1.1 ~ 21.3）显著增加SPR，而SERM联合激肽酶可显著增加精子浓度（MD = 16.5 × 10⁶ mL^–1, 95% CI为1.6 × 10⁶ ~ 31.4 × 10⁶)，SERM联合辅酶Q₁₀则显著改善前向活力精子（MD = 11.3%, 95% CI为7.3% ~ 15.4%）和正常形态精子（MD = 11.2%, 95% CI为 5.4% ~ 16.9%）。在不良反应方面，脂肪酸补充剂和己酮可可碱分别与口臭或味觉差（RR = 8.1, 95% CI为1.0 ~ 63.5）和呕吐（RR = 8.0, 95% CI为1.0 ~ 63.0）相关。综上所述，对于改善不育男性配偶活产率的最佳治疗方案仍然不清楚。对于所有不孕夫妇和男性少弱精症不孕夫妇，卡尼汀联合维生素和FSH方案在成功实现自然妊娠方面分别优于其他方案。其他治疗方法对妊娠结局的疗效仍需要进一步验证。

关键词：男性不育症药物补充剂自然妊娠率精子参数

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DDB1- and CUL4-associated factor 8 plays a critical role in spermatogenesis

Xiuli Zhang, Zhizhou Xia, Xingyu Lv, Donghe Li, Mingzhu Liu, Ruihong Zhang, Tong Ji, Ping Liu, Ruibao Ren

《医学前沿（英文）》 2021年第15卷第2期页码 302-312 doi: 10.1007/s11684-021-0851-8

摘要： Cullin-RING E3 ubiquitin ligase (CRL)-4 is a member of the large CRL family in eukaryotes. It plays important roles in a wide range of cellular processes, organismal development, and physiological and pathological conditions. DDB1- and CUL4-associated factor 8 (DCAF8) is a WD40 repeat-containing protein, which serves as a substrate receptor for CRL4. The physiological role of DCAF8 is unknown. In this study, we constructed knockout mice. Homozygous mice were viable with no noticeable abnormalities. However, the fertility of deficient male mice was markedly impaired, consistent with the high expression of DCAF8 in adult mouse testis. Sperm movement characteristics, including progressive motility, path velocity, progressive velocity, and track speed, were significantly lower in knockout mice than in wild-type (WT) mice. However, the total motility was similar between WT and knockout sperm. More than 40% of spermatids in knockout mice showed pronounced morphological abnormalities with typical bent head malformation. The acrosome and nucleus of knockout sperm looked similar to those of WT sperm. tests showed that the fertilization rate of knockout mice was significantly reduced. The results demonstrated that DCAF8 plays a critical role in spermatogenesis, and DCAF8 is a key component of CRL4 function in the reproductive system.

关键词： Dcaf8 male infertility spermatogenesis

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Cell therapy for the treatment of reproductive diseases and infertility: an overview from the mechanism

《医学前沿（英文）》 2022年第16卷第6期页码 827-858 doi: 10.1007/s11684-022-0948-8

摘要： Infertility is experienced by 8%–12% of adults in their reproductive period globally and has become a prevalent concern. Besides routine therapeutic methods, stem cells are rapidly being examined as viable alternative therapies in regenerative medicine and translational investigation. Remarkable progress has been made in understanding the biology and purpose of stem cells. The affected pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs) are further studied for their possible use in reproductive medicine, particularly for infertility induced by premature ovarian insufficiency and azoospermia. Accordingly, this study discusses current developments in the use of some kinds of MSCs such as adipose-derived stem cells, bone marrow stromal cells, umbilical cord MSCs, and menstrual blood MSCs. These methods have been used to manage ovarian and uterine disorders, and each technique presents a novel method for the therapy of infertility.

关键词： infertility stem cell therapy mesenchymal stem cells pluripotent stem cells

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244对有不良孕产史夫妇初次染色体断裂率检测结果分析

余宏亮,常明秀,曹恒海,薄立伟,王艳丽,吴艳红

《中国工程科学》 2014年第16卷第5期页码 67-69

摘要：

为了了解有不良孕产史夫妇的染色体断裂率的发生情况，笔者对来河南省人口和计划生育科学技术研究院就诊的有不良孕产史夫妇的染色体断裂率分析的检查结果进行统计学分析。分析结果显示：男性患者的就诊年龄平均为29.07 岁，女性患者的就诊年龄平均为28.15 岁，年龄与染色体检测结果间无相关。男性患者中未发现断裂的占男性总数的32.38 %，女性患者中未发现染色体断裂的占女性总数的37.7 %；男性染色体断裂率为1 的占男性总数的38.11 %，女性染色体断裂率为1 的占女性总数的34.43 %；男性染色体断裂率为2 的占男性总数的21.72 %，女性染色体断裂率为2 的占女性总数的23.36 %；男性染色体断裂率为3 的占男性总数的7.79 %，女性染色体断裂率为3 的占女性总数的2.87 %；女性染色体断裂率为4 的占女性总数的0.82 %；女性染色体断裂率为6 的占女性总数的0.41 %；女性染色体断裂率为9 的占女性总数的0.41 %。男性患者的染色体断裂率均值无差别（P>0.05）。男、女患者的染色体断裂率均值在1.01，患者平均年龄为29.53 岁，经检查有染色体断裂占64.96 %。通过研究发现，染色体断裂率增高可能是引起夫妇中发生胎停、流产、胎儿发育不良等不良孕产现象的重要原因之一。

关键词：不育夫妇不良孕产染色体断裂率

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通过组学将中医体质理论应用于不孕症

王琦

《工程（英文）》 2023年第30卷第11期页码 30-31 doi: 10.1016/j.eng.2023.05.005

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Susceptibility of male and female Japanese medaka (

Nannan LIU, Mei MA, Yiping XU, Jinmiao ZHA, Kaifeng RAO, Zijian WANG

《环境科学与工程前沿（英文）》 2013年第7卷第1期页码 77-84 doi: 10.1007/s11783-012-0466-z

摘要： 2,4,6-trichlorophenol (2,4,6-TCP) is a widespread probable human carcinogen and has been proven to have genotoxicity in assays. However, little genotoxicity information and no micronuclei induction data for 2,4,6-TCP is available from tests, especially for sex-specific differences. Following a preliminary test, a piscine peripheral erythrocyte micronucleus assay was conducted on medaka ( ) after a 28-day exposure to 2,4,6-TCP. In the present study, the mean micronuclei (MNC) frequencies of all of the groups increased in a dose-dependent manner, which indicated the potential genotoxicity of 2,4,6-TCP. Moreover, males were found to be more susceptible compared with females after a 28-day exposure to 2,4,6-TCP in all of the dosed groups above 10 μg·L . This is the first report on the potential of micronuclei induction and a sex-susceptible effect in the peripheral erythrocytes of mature fish after 2,4,6-TCP exposure.

关键词： 2 4 6-trichlorophenol genotoxicity Japanese medaka piscine micronucleus test in peripheral erythrocytes gender difference

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重庆市男性绝育术后并发症市级鉴定情况分析

李川海,马明福,杨皓,周署平

《中国工程科学》 2014年第16卷第5期页码 110-112

摘要：

2012—2013年根据国家卫生和计划生育委员会发布的《计划生育手术并发症鉴定管理办法（试行）》和《计划生育手术并发症鉴定分级标准（试行）》，通过填写重庆市统一的计划生育手术并发症鉴定申请表，对重庆市部分区（县）进行了计划生育手术并发症鉴定，并对市级鉴定情况进行了探讨。结果表明：2012—2013 年申请男性绝育术后并发症市级鉴定的56 例中，符合男性绝育术后并发症的有10 例，占申请人数的25.2 %；自述症状中有25 例与男性绝育术后并发症无关，占44.64 %；符合男性绝育术后并发症的都是20 世纪90 年代以前进行的绝育术。因此，男性绝育术后并发症鉴定应严格执行鉴定标准，做到公平、公开、公正，应做好男性绝育术相关知识的宣传，加强对老年病科普知识的宣传，并加强计划生育技术服务队伍的建设。

关键词：男性绝育术并发症市级鉴定技术服务

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Immunohistochemical measurement and expression of Mcl-1 in infertile testes

null

《医学前沿（英文）》 2015年第9卷第3期页码 361-367 doi: 10.1007/s11684-015-0395-x

摘要：

The diagnosis of azoospermia represents a major challenge to andrologists as this condition may occur despite normal spermatogenesis and genital tracts. Myeloid cell leukemia-1 (Mcl-1) is a member of the Bcl-2 family of proteins involved in regulation of apoptosis in various cell types. This study aimed to investigate the immunohistochemical expression of Mcl-1 in testicular biopsies of subjects with azoospermia. Eighty-six cases with azoospermia were obtained from 509 infertile patients admitted to the Andrology Unit of the Zagazig University Hospitals from January 2010 to December 2011. Biopsies were diagnosed and classified using H&E-stained slide sections. The specimens were subjected to immunohistochemical staining for Mcl-1 and examined through light microscopy. Forty-five cases of maturation arrest (25 at spermatids and 20 at the spermatocytes), 31 cases of hypospermatogenesis (20 moderate and 11 severe), 5 cases of Sertoli?cell-only syndrome, 2 cases of basement membrane hyalinization, and 1 case of tubular and peritubular sclerosis were observed. Normal spermatogenesis was detected in 2 cases. A strong positive immunoreaction in Leydig cells was observed among all investigated specimens. A moderate reaction was detected in spermatocytes and spermatozoa in cases of normal spermatogenesis and hypospermatogenesis, but a negative reaction was detected in cases of maturation arrest and germ cell aplasia. Apoptosis was found to be associated with decreased rate of spermatogenesis. High apoptosis rates may result in azoospermia, which can occur despite normal spermatogenesis and absence of duct obstruction.

关键词： spermatogenesis testis Mcl-1 expression immunohistochemical study infertility

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A 7-year follow-up study of the features and transformations of elderly male patients with OGTT-1h hyperglycemia

TIAN Hui, LI Chunlin, ZHONG Wenwen, PAN Changyu, LU Juming, CAO Xiutang

《医学前沿（英文）》 2008年第2卷第4期页码 396-399 doi: 10.1007/s11684-008-0076-0

摘要： The aim of this paper is to investigate the clinical features and transformation of elderly male patients with normal blood glucose levels at fasting and 2 hours after glucose intake but with hyperglycemia (≥ 11.1 mmol/L) 1 hour after oral glucose tolerance test (OGTT-1h HG). Seven years of follow-up visits were performed on 189 elderly male outpatients with OGTT-1h HG and data was recorded on their body mass index (BMI), blood pressure, serum cholesterol and triglyceride test results and on their glucose tolerance changes every 1–2 years after taking OGTT; their possible causes were analysed. Follow-up visits revealed that 19 patients with OGTT-1h HG were diagnosed with diabetes (10.1%), 78 patients with impaired glucose tolerance (IGT, 41.3%), 2 patients transformed to normal glucose tolerance (NGT, 1.1%) and the remaining 90 patients (47.6%) remained unchanged. Synchronized comparison with IGT patients showed that the ratio of OGTT-1h HG patients turning to diabetes was lower than that of IGT patients (21.1%, = 13.05, < 0.01), and the ratio of OGTT-1h HG patients transforming to NGT was slightly higher (0.4%, = 2.46, > 0.05). The prevalence of complications of hypertension, coronary heart disease, cerebral vascular diseases and dyslipidemia in patients with OGTT-1h HG were higher than those with NGT ( < 0.05) and were similar to that of IGT patients. As a special phenotype of OGTT and as part of an abnormal glucose tolerance conformation, patients with OGTT-1h HG warrant special attention, since about half of them were found to have developed diabetes or IGT, and their risk of suffering from vascular diseases were also increased.

关键词： special attention prevalence unchanged dyslipidemia elderly

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多囊卵巢综合征无排卵的胰岛素信号和雄激素合成的新遗传风险和代谢特征 Article

吴效科, 黄志超, 曹义娟, 李建, 李志强, 马红丽, 高敬书, 常惠, 张多加, 丛晶, 王宇, 吴奇, Xiaoxiao Han, Pui Wah Jacqueline Chung, Yiran Li, Xu Zheng, Lingxi Chen, Lin Zeng, Astrid Borchert, Hartmut Kuhn, Zi-Jiang Chen, Ernest Hung Yu Ng, Elisabet Stener-Victorin, 张和平, Richard S. Legro, Ben Willem J. Mol, 师咏勇

《工程（英文）》 2023年第23卷第4期页码 103-111 doi: 10.1016/j.eng.2022.08.013

摘要：

促排卵是多囊卵巢综合征（PCOS）不孕症的一线治疗方案。卵巢对促排卵治疗的排卵应答差被认为与胰岛素抵抗和高雄激素血症相关。在一个包含1000名PCOS不孕妇女（PCOSAct）的前瞻性队列中，我们开展了一项全外显子联合靶向单核苷酸多态性（SNP）测序以及代谢组学研究。在全基因组水平找出与无排卵显著相关的常见变异和罕见突变，并通过机器学习算法构建排卵预测模型。研究发现，ZNF438基因中标记为rs2994652 (p=2.47×10^–8)的常见变异和REC114基因中的一个罕见功能突变（rs182542888，p=5.79×10^–6）与促排卵治疗失败显著相关。携带rs2994652 A等位基因和REC114 p.Val101Leu (rs182542888)的PCOS不孕妇女进行促排卵治疗的总排卵率更低（分别为：比值比（OR）=1.96，95% 置信区间（CI）[1.55~2.49]；OR=11.52，95% CI [3.08~43.05]），出现排卵的间隔时间更长（平均56.7天vs.49.0天，p<0.001；78.1天vs.68.6天，p=0.014）。对于rs2994652突变者，L-苯丙氨酸水平升高并与胰岛素抵抗稳态模型（HOMA-IR）指数（r=0.22, p=0.05）和空腹血糖（r=0.33, p=0.003）呈正相关；对于rs182542888突变者，花生四烯酸代谢产物水平下降并与升高的抗苗勒管激素（r=－0.51, p=0.01）和总睾酮（r=－0.71, p=0.02）呈负相关。整合基因变异位点、代谢产物及临床特征的联合预测模型可提高对排卵的预测能力[曲线下面积（AUC）=76.7%]。ZNF438基因的一个常见变异和REC114基因的一个罕见功能突变，以及与二者相关的苯丙氨酸和花生四烯酸代谢物改变，与PCOS女性不孕症的促排卵治疗失败相关。