BackgroundDiabetes mellitus (DM) is one of the most common endocrine disorders affecting various physiological systems and tissues, including the reproductive organs in men. However, the consequences of DM for male individuals undergoing assisted reproductive technology (ART) remain unclear.ObjectiveTo investigate the sperm quality and the outcomes of in vitro fertilization - embryo transfer (IVF-ET) and intracytoplasmic sperm injection - embryo transfer (ICSI-ET) in patients with type 2 diabetes mellitus (T2DM).MethodsWe retrospectively analyzed data from 318 infertile couples for IVF/ICSI cycle outcomes. The experimental group included 106 infertile couples (with male partners all diagnosed with T2DM) who underwent ART treatment at our center. The negative control group consisted of 212 non-diabetic infertile couples, matched by male/female body mass index (BMI) (± 1 kg/m²), male/female age (± 2 years), and serum anti-Müllerian hormone (AMH) levels (± 2 ng/mL). Patients were categorized into two groups based on clinical pregnancy. The χ² test and logistic regression analysis were used to identify and determine the influencing factors of clinical pregnancy.ResultsInfertile men with T2DM had significantly lower sperm volume (2.4 ± 2.2 vs. 2.7 ± 1.2, P < 0.01) and significantly decreased sperm motility compared to the control group (23.0 ± 17.2 vs. 29.7 ± 15.3, P < 0.01). In IVF/ICSI cycles, both groups exhibited similar results in two-pronuclear (2PN) fertilization rates and high-grade embryo rates (p > 0.05). The implantation rate, clinical pregnancy rate, and miscarriage rate also showed no significant differences (p > 0.05).ConclusionT2DM in infertile men exerts adverse effects on sperm quality; however, the decline in sperm quality did not translate into compromised clinical ART outcomes.

Background: Centromere protein A (CENPA) is a histone H3 variant essential for centromere function and has been implicated in tumorigenesis in several cancers. However, its clinical significance and biological role in endometrial cancer (EC) remain poorly characterized. This study aimed to elucidate the oncogenic function and underlying mechanisms of CENPA in EC progression. Methods: CENPA expression and its correlation with patient survival were analyzed using clinical datasets and tissue samples. Gain- and loss-of-function assays were performed to evaluate the effects of CENPA on EC cell proliferation, migration, and invasion. Metabolic assays, protein interaction studies, and in vivo xenograft models were utilized to investigate the molecular mechanisms driving CENPA-mediated tumorigenesis. Results: CENPA was significantly upregulated in EC tissues compared to normal endometrium, and high expression correlated with poor overall survival. Functionally, CENPA overexpression promoted, while its silencing suppressed, EC cell growth and metastasis. Mechanistically, CENPA facilitated metabolic reprogramming by enhancing aerobic glycolysis. We identified Yin Yang 1 (YY1) as a direct binding partner of CENPA. CENPA stabilized YY1 protein levels by inhibiting its proteasomal degradation. Importantly, YY1 knockdown rescued the glycolytic and tumorigenic phenotypes induced by CENPA both in vitro and in vivo. Conclusions: Our findings establish CENPA as a critical oncogenic driver in EC that functions by stabilizing YY1 to promote metabolic reprogramming. The CENPA-YY1 axis may represent a potential therapeutic target for EC.

Intimate partner violence (IPV) and infertility are significant global health and human rights concerns. Evidence has shown that infertile women face a higher risk of IPV, yet national-level data on its prevalence remain limited. This study aims to quantify the prevalence of IPV against infertile women in China and identify associated risk factors. A national cross-sectional study was conducted in China from October 2021 to August 2022, using multistage stratified cluster sampling. Infertile women were recruited from 30 reproductive centers across ten provinces. A self-administered questionnaire, including the Revised Conflict Tactics Scale (CTS-2) and the Scale of Economic Abuse-12 (SEA-12), measured IPV in the past 12 months and over a lifetime. A structural equation model (SEM) explored risk factors for past-12-month IPV victimization. A total of 12,392 infertile women were included. The weighted 12-month prevalence of IPV was 34.1

Polycystic ovary syndrome (PCOS) affects 6%-10% of women of reproductive age and is known to be associated with disruptions in the gut bacteria. However, the role of the gut mycobiota in PCOS pathology remains unclear. Using culture-dependent and internal transcribed spacer 2 (ITS2)-sequencing methods, we discovered an enrichment of the gut-colonizable fungus Aspergillus tubingensis in 226 individuals, with or without PCOS, from 3 different geographical areas within China. Colonization of mice with A. tubingensis led to a PCOS-like phenotype due to inhibition of Aryl hydrocarbon receptor (AhR) signaling and reduced interleukin (IL)-22 secretion in intestinal group 3 innate lymphoid cells (ILC3s). By developing a strain-diversity-based- activity metabolite screening workflow, we identified secondary metabolite AT-C1 as an endogenous AhR antagonist and a key mediator of PCOS. Our findings demonstrate that an intestinal fungus and its secondary metabolite play a critical role in PCOS pathogenesis, offering a therapeutic strategy for improving the management of the disease.

BACKGROUND:Recent research has indicated a close connection between the three-dimensional (3D) structure of chromatin and early embryo development, with precise higher-order chromatin folding playing a significant role in mediating gene expression. However, the specific role of 3D genomic hierarchical structure and its dynamics in early embryo development remains largely unknown. RESULTS:In this study, we examined the hierarchical topological association domain (TAD) during early embryo development and its relationship with zygotic gene activation (ZGA), gene expression, and chromatin accessibility to gain a better understanding of the dynamics of TAD nesting levels during this developmental stage. Our findings show that ZGA precedes the establishment of hierarchical TAD, leading to widespread gene expression, an increase in the percentage of high-level TAD structures, and enhanced chromatin accessibility at higher hierarchical levels. Additionally, we utilized a deep neural network to investigate the formation of TAD boundaries and found that histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine trimethylation (H3K27me3) are key features in the establishment of TAD boundaries. Furthermore, we observed heterogeneous dynamics of hierarchical TAD among different species. CONCLUSIONS:Overall, our study sheds light on the folding dynamics of hierarchical TADs during early embryo development and underscores their close relationship with transcriptional programs.

Purpose: To investigate the combined effects of super-active platelet lysate (sPL) and acellular amniotic membrane (AAM) in promoting endometrial repair and enhancing endometrial receptivity in rats. Methods: The characteristics of sPL-AAM were examined through scanning electron microscopy, contact angle tester, and release experiments. We aimed to establish a rat model for endometrial injury. We divided sixty-four rats into four groups: the Injury group (Control group), the AAM group, the sPL group, and the sPL-AAM group. Our study compared the endometrial thickness, gland count, and fibrotic area recovery in rats at 6 days and 18 days post-treatment. Immunohistochemistry was utilized to assess the expressions of CD34 and ANG. Additionally, we used ELISA to detect the levels of IL-6 and TNF-alpha, while Western Blot was employed to compare the expressions of CK19, Integrin (33, and TGF-(31. One month after the treatment, we evaluated and compared the pregnancy recovery among the groups. Results: Compared to the Injury group, the sPL-AAM group demonstrated enhanced endometrial regeneration in rats at both 6 days and 18 days post-treatment, resulting in a favorable pregnancy outcome. This was achieved by promoting angiogenesis, suppressing the inflammatory response, and reducing fibrosis. The observed effects were superior to those of the sPL group alone. While sPL, when administered alone, showed some degree of endometrial restoration at 6 days post-treatment, its efficacy was diminished at 18 days post-treatment. The impact of AAM alone appeared inconspicuous compared to the injury group. This suggests that sPL serves as the primary agent in facilitating endometrial repair, while AAM functions as a carrier to extend the duration of sPL's effectiveness. Conclusion: sPL-AAM can release effective cytokines, repair endometrial damage in rats, enhance endometrial receptivity, and ultimately improve pregnancy outcomes.

Objective Circular RNAs (circRNAs) are involved in the development of human cancers, including cervical cancer (CC). However, the role and mechanism of circ_0006789 (circSLC25A43) in CC are unclear. The purpose of this study was to investigate the functional role of circ_0006789 in CC.Methods The expression of circ_0006789 in CC tissues and cell lines was examined by RT-qPCR. The characterization of circ_0006789 in CC cells was verified by subcellular localisation, actinomycin D assay, and RNase R assay. After circ_0006789 was knocked down in CC cell lines, the proliferation, apoptosis, migration and invasion of CC cells were assessed by CCK-8 method, flow cytometry, and Transwell assay. RIP assay, FISH assay, dual luciferase reporter gene assay and Western blot were used to investigate the regulatory mechanism between circ_0006789, miR-615-5p and heat shock factor 1 (HSF1).Results circ_0006789 was upregulated in CC tissues and cell lines. CC cells were inhibited in their proliferation, migration, and invasion, as well as promoted to apoptosis when circ_0006789 was knocked down. It was found that circ_0006789 targeted miR-615-5p, and miR-615-5p expression was inversely correlated with circ_0006789 expression. Furthermore, HSF1 was a target gene of miR-615-5p. Furthermore, the suppressive effects on HeLa cells mediated by circ_0006789 knockdown were counter-balanced when miR-615-5p was knocked down and HSF1 was overexpressed. Mechanistically, circ_0006789 was found to promote CC development by reducing miR-615-5p and increasing HSF1 expressions.Conclusion circ_0006789 accelerates CC development via the miR-615-5p/HSF1 axis.

In mammals, during the post-fertilization pre-implantation phase, the expression of cell type-specific genes is crucial for normal embryonic development, which is regulated by cis-regulatory elements (CREs). TFs control gene expression by interacting with CREs. Research shows that transcription factor binding sites (TFBSs) reflect the general characteristics of the regulatory genome. Here, we identified TFBSs from chromatin accessibility data in five stages of early human embryonic development, and quantified transcription factor binding sites-clustered regions (TFCRs) and their complexity (TC). Assigning TC values to TFCRs has made it possible to assess the functionality of these regulatory elements in a more quantitative way. Our findings reveal a robust correlation between TFCR complexity and gene expression starting from the 8Cell stage, which is when the zygotic genome is activated in humans. Furthermore, we have defined long-range TFCRs (LR-TFCRs) and conjecture that LR-TFCRs may regulate gene expression through phase-separation mechanisms during the early stages of human embryonic development.

目的 探究双导-合作式情景模拟教学法在临床医学专业妇产科实习生教学中的应用.方法 选取 2020年 10 月—2022 年 1 月在哈尔滨医科大学附属第一医院参与妇产科教学的 98 名实习生,采取随机数字表法分为对照组和观察组,各 49 名,对照组给予常规教学法,观察组给予双导-合作式情景模拟教学法,两组均连续进行 1 个月教学,对比两组教学效果.结果 观察组实习生基础理论知识及临床操作技能评分均高于对照组,观察组对教学方法的评价结果优于对照组,差异有统计学意义(P＜0.05),带教老师对观察组实习生课堂表现的评价结果优于对照组,观察组实习生批判性思维能力指标得分均高于对照组,差异有统计学意义(P＜0.05).结论 双导-合作式情景模拟教学法应用于妇产科实习生教学中可明显提高实习生教学成绩,有利于培养实习生批判性思维能力,实习生课堂表现较好.

Objective:To analyze the prevalence and disease burden of male and female infertility in China from 1990 to 2019.Methods:The global disease burden database of 2019 was used to analyze the prevalence of male and female infertility and disability adjusted life years (DALY) in China from 1990 to 2019 among the total Chinese male and female population and different age groups.Results:In 2019, the number, prevalence, DALY and DALY rate of male infertility in China were 14 577 432, 2 011.18/100 000, 77 983 person years, 1 076/100 000, respectively. The number, prevalence, DALY and DALY rate of female infertility were 37 884 300, 5 431.22/100 000, 197 046 person years, 28.25/100 000, respectively. The prevalence and disease burden of female infertility were higher than those of male infertility. The age group with the highest male prevalence rate and DALY rate were 35-39 and 30-34 years old respectively, the age group with the highest female prevalence rate and DALY rate were 40-44 and 35-39 years old respectively, and the age group with the highest female prevalence rate and DALY rate was 5 years later than the male age group. From 1990 to 2019, the prevalence rate and DALY rate of male and female infertility increased in the first 20 years or so, and decreased in the last 10 years or so. The prevalence rate and DALY rate of male and female infertility in China were significantly higher than those in the whole world and different socio-demographic index (SDI) regions.Conclusion:Although the prevalence rate and DALY rate of male and female infertility in China have decreased in recent years, the population base of China is large, and the disease burden of male and female infertility in the world is still large. Active prevention and treatment measures should be taken to reduce the disease burden of male and female infertility.

目的 探讨研究团队情景模拟教育教学模式在临床妇产专业教学中的应用效果.方法 采取随机数字表法将本院自2020年9月至2022年6月接受临床妇产科教学的120名医学生分为对照组和观察组,每组各60名,对照组给予常规教学方法,观察组在对照组基础上实施团队情景模拟教育教学模式,对比两组考试成绩、教学效果、对教学方式的评价、对能力培养的自我评价、自我效能评估.结果 与对照组相比,观察组综合临床诊断、报告书写、专业基础理论知识评分均较高,差异有统计学意义(P＜0.05);观察组在提高学习兴趣、合作沟通能力、知识记忆理解能力、分析问题能力、解决问题能力等方面的医学生认可比例较高,差异有统计学意义(P＜0.05);观察组对教学方法感到满意、提高了对妇产科常见疾病的认识、更愿意主动学习、提高了自身对疾病诊断及教学的能力、对指导教师满意的医学生比例较高,差异有统计学意义(P＜0.05);观察组自我学习能力、多学科分析能力、临床思维能力、团队协作能力以及语言表达能力等对能力培养的自我评价认可的医学生比例较高,差异有统计学意义(P＜0.05);观察组中加大对临床妇产科常见疾病诊疗范围的了解、加深了解常见妇产科疾病的治疗手段、加深对妇产科疾病主要预后的了解程度、提高临床综合诊疗能力、对本学科的疑惑得到解答上的医学生比例较高,差异有统计学意义(P＜0.05).结论 团队情景模拟教育教学模式在临床妇产专业教学中可明显提高学生考试成绩和自我能力,改善自我效能,获得更好的教学效果.

目的 对比新鲜周期不同D3卵裂期胚胎移植策略的妊娠结局,优化移植策略.方法 回顾性分析2016年1月至2021年12月于哈尔滨医科大学附属第一医院生殖医学科行常规体外受精/卵胞浆内单精子显微注射(in vitro fertilization/intracytoplasmic sperm injection,IVF/ICSI)助 孕且为第一促排周期并行新鲜周期移植的2 251例患者的临床资料.根据移植胚胎个数及移植胚胎的质量不同分为移植两枚D3优质胚胎组(A组),移植1枚D3优质胚胎+1枚D3非优质胚胎组(B组),移植2枚D3非优质胚胎组(C组)和移植1枚D3优质胚胎组(D组).根据患者年龄分层,各组均再分为两个亚组,分别为≤35岁组和≥36岁组,对比各组间妊娠结局.结果 A、B、C、D四组患者活产率、临床妊娠率、种植率、多胎率、早期流产率和早产率比较,差异均有统计学意义(P＜0.05).在≤35岁患者亚组中,A1组、B1组、C1组和D1组活产率、临床妊娠率、种植率、多胎率、早期流产率和早产率比较,差异均有统计学意义(P＜0.05).A1组活产率高于B1组和D1组(P=0.003、P＜0.001),B1组和D1组活产率差异无统计学意义(P=0.021);A1组与B1组临床妊娠率高于D1组(P均＜0.001);A1组的种植率高于B1组(P=0.004),与D1组差异无统计学意义(P=0.541);A1组与B1组的多胎率和早产率均高于D1组(P＜0.001、P＜0.001,P=0.011、P=0.007);B1组的早期流产率高于A1组(P=0.004).在≥36岁患者亚组中,A2组、B2组、C2组和D2组活产率、临床妊娠率、种植率和多胎率比较,差异均有统计学意义(P＜0.05),而早期流产率和早产率比较,差异无统计学意义(P＞0.05).A2组的活产率和妊娠率高于D2组(P=0.011、0.001).A2组种植率高于B2组(P=0.003).A2组多胎率高于D2组(P=0.008).各组间早期流产率和早产率差异无统计学意义(P＞0.05).活产的二分类多因素Logistic回归分析结果显示,不同胚胎移植策略、年龄以及不同促排卵方案均是活产的独立影响因素.结论 对于年龄≤35岁的患者,第一周期首选移植1枚D3优质胚胎是较为适合的移植策略,而对于年龄≥36岁的患者,当患者有≥2枚D3优质胚胎时,第一周期可优先移植2枚优质胚胎以保证单次成功率;而当患者仅有1枚D3优质胚胎时,则建议给予1枚优质胚胎+1枚非优质胚胎的移植策略.

子宫内膜异位症( endometriosis,EMs)是一种治愈率低且复发率高的妇科疾病,累及10％ ～15％的育龄妇女[1].EMs在我国的发病率有显著增高的趋势,有研究显示,80％的EMs患者伴有盆腔痛,50％合并不孕,严重影响中青年妇女健康和生活质量[2].

随着女性生育年龄的推迟以及多胎政策的放开,越来越多患有子宫肌瘤的育龄女性会因有生育意愿而就诊.2017年Stewart EA等[1]发表的子宫肌瘤流行病调查显示,生育年龄女性因子宫肌瘤而就诊约有25％.有研究显示约20％ ～30％的子宫肌瘤患者会并发不孕, 2％ ～3％的女性中子宫肌瘤可能是导致不孕的唯一原因[2].纵观肌瘤对生育的影响主要有以下几种:①黏膜下肌瘤会影响子宫腔的形态、阻塞宫颈管或阻塞输卵管开口,压迫内膜导致腺体发育不良,影响受精卵着床[3];② 过大的肌壁间肌瘤会导致宫腔形态改变,影响子宫血液循环及子宫蠕动,影响受精卵着床及早期胚胎发育[4];③ 妊娠期出现的肌瘤变性、迅速生长增大会引发疼痛及诱发早产的发生[5].而浆膜下肌瘤因其远离子宫腔、对妊娠及生育影响较小[6].

During early mammalian embryo development, different epigenetic marks undergo reprogramming and play crucial roles in the mediation of gene expression. Currently, several databases provide multi-omics information on early embryos. However, how interconnected epigenetic markers function together to coordinate the expression of the genetic code in a spatiotemporal manner remains difficult to analyze, markedly limiting scientific and clinical research. Here, we present dbEmbryo, an integrated and interactive multi-omics database for human and mouse early embryos. dbEmbryo integrates data on gene expression, DNA methylation, histone modifications, chromatin accessibility, and higher-order chromatin structure profiles for human and mouse early embryos. It incorporates customized analysis tools, such as “multi-omics visualization,” “Gene&Peak annotation,” “ZGA gene cluster,” “ cis -regulation,” “synergistic regulation,” “promoter signal enrichment,” and “3D genome.” Users can retrieve gene expression and epigenetic profile patterns to analyze synergistic changes across different early embryo developmental stages. We showed the uniqueness of dbEmbryo among extant databases containing data on early embryo development and provided an overview. Using dbEmbryo, we obtained a phase-separated model of transcriptional control during early embryo development. dbEmbryo offers web-based analytical tools and a comprehensive resource for biologists and clinicians to decipher molecular regulatory mechanisms of human and mouse early embryo development.

子宫内膜异位症( endometriosis,EMs) ,指子宫腔外存在子宫内膜样组织,它是一种与不孕症相关的常见疾病,患病后许多女性会出现慢性疼痛[1].其潜在的病理生理机制包括增殖、凋亡、自噬、迁移、侵袭、纤维化、血管生成、氧化应激、炎症和免疫逃逸等[2] ,该病的确切发病机制尚不清楚,但是,EMs是一种雌激素依赖的疾病,已知其特征是异位子宫内膜的雌激素依赖性生长以及局部雌激素分泌增加[3].

Endometrial cancer (EC) is one of the three fatal tumors of the female reproductive system. Epigenetic alterations have been reported to be important in tumorigenesis, especially the chromatin accessibility changes and transcription factor binding differences. However, the regulatory mechanism underlying epigenetic alterations in EC development remains unclear. Here, we identified and characterized transcription factor binding site clustered regions (TFCRs) by integrating chromatin accessibility and transcription factor binding information. We totally identified 78,820 TFCRs and explored the relationship between TFCRs and regulatory elements, gene expression and mutation. Finally, we constructed a bioinformatic framework to identify candidate oncogenes and screened 13 candidate key genes, which may serve as potential diagnostic markers or therapeutic targets of EC.

子宫内膜异位症(endometriosis,EMs)是一种极具复发性和侵袭性的良性疾病,严重影响育龄女性的生活质量.目前临床上缺乏有效的生物标志物,是造成诊断延迟的重要原因之一.随着疾病的进一步进展,EMs给患者带来严重的健康损害和经济负担.目前,腹腔镜检查是确诊EMs的方法,但因其有创、手术并发症及费用昂贵等特点,限制了临床应用.探索敏感度和特异度均佳的生物标志物对于EMs的无创性早期诊断至关重要.微小RNA(microRNA,miRNA)是一类非编码小分子RNA,具有高度的组织特异性和稳定性,近年研究表明miRNA可作为EMs诊断的潜在生物标志物,早期识别有助于对患者的及时诊断和优化治疗.综述miRNA在EMs中的研究进展.

目的:探究哺乳动物早期胚胎发育过程中基因表达调控信息的变化规律.方法:收集小鼠早期胚胎发育各时期的RNA-seq,ATAC-seq,MethylC-Seq和H3K4me3 ChIP-seq数据进行整合分析,观察小鼠早期胚胎发育各时期转录因子表达量的变化,计算各时期基因表达量与转录因子结合位点数量及染色质可及性的相关性,筛选各时期表达量前10％的基因,统计其表达量和转录因子占比,并进行启动子可及性分析.根据前期报道的转录因子三节点调控网络,对早期胚胎各时期转录因子调控网络的富集模式进行分析.根据多组学数据分析结果,推测早期胚胎发育调控过程中转录因子和表观遗传修饰信息的共调控模型.结果:转录因子数量和调控关系变化以及染色质可及性、DNA甲基化修饰、组蛋白修饰等表观遗传修饰共同调控早期胚胎发育各时期的基因表达,这些因素在不同时期发挥不同程度的调控作用.结论:转录因子和表观遗传修饰在早期胚胎发育过程中动态调控基因表达.

子宫内膜异位症(EMs)是一种严重影响女性生活质量与生育能力的常见妇科良性疾病,其复杂的病理生理学机制尚未明确.尽管EMs的诊断标准与治疗方案在不断改进,但其高发病率与低治愈率却没有明显改善.维甲酸(RA)作为维生素A的活性代谢产物,参与各种细胞生长、分化与器官发生的过程.RA在EMs中因代谢缺陷而呈异常低水平,且大量研究显示RA信号缺陷可能通过提高局部内膜雌激素水平、抑制凋亡与自噬、促炎与异常免疫调节等方式参与EMs的发生、发展,因此RA及其衍生物有望成为EMs治疗的新药物.就EMs中RA异常代谢、RA信号缺陷促进EMs发生和发展的可能机制以及RA在EMs中的治疗潜力进行了综述,以期为EMs的发病机制与治疗提供新思路.