Cervical insufficiency (CI) affects 0.1%-2% of pregnancies and represents a significant cause of second-trimester pregnancy loss and preterm birth; yet, its pathophysiology remains incompletely understood. This study investigated whether aquaporin-3 (AQP3) facilitates hydrogen peroxide (H₂O₂) transport into cervical macrophages, driving their polarization toward a pro-inflammatory phenotype and subsequent cervical matrix degradation. Cervical tissues from women with CI demonstrated 1.45-fold higher AQP3 expression compared to gestational age-matched controls, with increased colocalization with macrophages. Tissue H₂O₂ levels were elevated 2.43-fold in CI, accompanied by increased oxidative damage markers and reduced collagen content. In vitro studies using THP-1 macrophages revealed that AQP3 knockdown prevented intracellular H₂O₂ accumulation despite pro-inflammatory stimulation, blocking M1 polarization and NF-κB activation. Co-culture experiments demonstrated that AQP3-dependent M1 macrophages increased matrix metalloproteinase (MMP)-9 activity 3.8-fold and reduced fibroblast collagen content by 59%. Both H₂O₂ scavenging with PEG-catalase and NF-κB inhibition with Bay 11-7082 prevented macrophage-mediated matrix degradation. These findings suggest that AQP3 may serve as an important mediator linking oxidative stress to inflammatory cervical remodeling through facilitation of H₂O₂ influx, NF-κB activation, and M1 macrophage polarization. Targeting AQP3 or its downstream signaling may represent a potential therapeutic approach that requires preclinical validation to prevent CI-associated pregnancy complications.

BackgroundThis study was performed to characterize the relationship of various laboratory test indicators with clinical information and Preeclampsia (PE) development. Then, prediction models for early-onset preeclampsia (EOPE), late-onset preeclampsia (LOPE), and preterm preeclampsia (Preterm PE) were developed using maternal characteristics and laboratory data.MethodsBetween January 2019 and December 2021, we retrospectively recruited 144 EOPE, 363 LOPE, 231 Preterm PE, and 1458 healthy participants from six hospitals. We utilized all available clinical and laboratory data obtained during routine prenatal visits in early pregnancy. The models for EOPE, LOPE, and Preterm PE were created using ensemble machine learning models with patient clinical and laboratory data. Results: By comparing laboratory variables between PE patients and healthy controls, we identified 7, 18, 8, 15, 7,29 laboratory markers for EOPE, LOPE, and Preterm PE, severe PE, superimposed PE, first-time PE respectively. The ensemble EOPE and LOPE models incorporating clinical and laboratory predictors outperformed the clinical factor models respectively. The ensemble EOPE model demonstrated good sensitivity (72.22%,95% confidence interval [CI]: 57.59%-86.85%) and specificity (85.25%,95% CI: 80.54%-89.97%) in distinguishing EOPE from controls in early pregnancy. Similarly, the ensemble LOPE model showed good accuracy in differentiating LOPE from healthy participants (sensitivity: 69.57%, 95% CI: 56.27%-82.86%; specificity: 85.25%, 95% CI: 80.54%-89.97%). The prediction scores demonstrated notable positive correlations with blood pressure at admission, while they showed inverse correlations with 24-hour urine protein levels and fetal growth restriction among PE patients. In conclusion, our study identified key laboratory indicators for forecasting PE. The developed models exhibited good predictive capability for assessing preeclampsia risk and severity based on clinical and laboratory data.Clinical trial numberNot applicable.

Preterm birth (PTB) significantly contributes to maternal and perinatal mortality and lifelong morbidity. While large language models (LLM) offer considerable potential for disease risk prediction and early detection, their application to PTB prediction using multi-omics data remains limited. We developed a novel transformer-based architecture for integrating cell free (cfDNA) and cfRNA sequencing data for PTB risk prediction. In the test set, the cfDNA LLM model achieved an AUC of 0.822, and the cfRNA LLM model achieved 0.851. Integrating cfDNA and cfRNA data within the transformer-based framework outperformed both, reaching an AUC of 0.890, a significant improvement over single-modality models. Additionally, we explored cfRNA and cfDNA integration using RNA editing and achieved an AUC of 0.82. This underscores the potential of multi-omics data fusion, with transformer-based architectures providing a powerful framework for disease risk assessment, and demonstrates the potential of AI-driven multi-omics for broader applications in precision obstetrics and biomedicine.

The China Prospective Multi-Center Birth Cohort Study was launched in 2022. In collaboration with medical centers in 12 cities, it aims to establish a high-quality, multidimensional cohort comprising 20,000 natural pregnancy and assisted reproductive families. As of June 26, 2024, 12,911 pregnant women have participated in this study, and 161,122 biological samples have been collected. These samples cover four critical periods (early pregnancy, mid-pregnancy, late pregnancy, and postpartum) and comprise 10 different types such as serum, plasma, and urine. The study has collected comprehensive information from early pregnancy to newborns. The participants have an average age of 29.76 years, an average height of 160.46 cm, an average pre-pregnancy BMI of 23.11, and an average BMI of 27.25 before delivery. The cohort includes individuals from 26 ethnic groups, with 25 minority groups comprising 5.03

Mesenchymal stem cells (MSCs) are a population of multipotent cells with remarkable regenerative and immunomodulatory properties. Wharton's jelly (WJ) from the umbilical cord (UC) has gained increasing interest in the biomedical field as an outstanding source of MSCs. However, challenges such as limited supply and lack of standardization in existing methods have arisen. This article presents a novel method for enhancing MSC yield by dissecting intact WJ from the umbilical cord. The method employs blunt dissection to remove the epithelial layer, maintaining the integrity of the entire WJ and resulting in an increased quantity and viability of harvested MSCs. This approach significantly reduces WJ waste compared to conventional sharp dissection methods. To ensure the purity of WJ-MSCs and minimize external cellular influence, a procedure utilizing internal tension to peel off the endothelium after flipping the UC was conducted. Additionally, the Petri dish was inverted for a short time during explant culture to improve attachment and cell outgrowth. Comparative analysis demonstrated the superiority of the proposed method, showing a higher yield of WJ and WJ-MSCs with better viability than traditional methods. The similar morphology and expression pattern of cell surface markers in both methods confirm their characterization and purity for various applications. This method provides a highyield and high-viability approach for WJ-MSC isolation, demonstrating great potential for the clinical application of MSCs.

Preterm birth (PTB), a leading cause of neonatal mortality, presents challenges in prediction with current methods focusing on traditional risk factors or biomarkers, particularly for spontaneous preterm birth (sPTB). Here, we developed a machine-learning framework based on untargeted cervicovaginal fluid proteomics from 707 individuals (136 sPTB and 571 FTB, Full-term birth) across five hospitals. Our analysis identified 293 proteins with potential predictive value, subsequently distilled into a robust predictive model composed of five protein markers (LUM, AMBP, B2M, FN1, and TIMP1) demonstrating outstanding performance in predicting the risk of sPTB. It achieved area under the receiver operating characteristic curve values of 0.89, 0.90, 0.92, and 0.94 in independent validation datasets from four hospitals, with an overall sensitivity = 0.73 and specificity = 0.92. Moreover, we reproduced the predictive performance of these five biomarkers using enzyme-linked immunosorbent assay (ELISA). At system level, integrating proteomics data from all hospitals, we delineated two distinct molecular subtypes of sPTB, revealing functional differences. Concurrently, we conducted a drug target analysis, unveiling potential preventative drugs for sPTB. In summary, this research expands the repertoire of sPTB prediction biomarkers, offers a novel non-invasive predictive model for sPTB and provides valuable data resources for further investigation into the pathogenesis of preterm birth.

Skin, the largest organ of body, is a highly immunogenic tissue with a diverse collection of immune cells. Highly polymorphic human leukocyte antigen (HLA) molecules have a central role in coordinating immune responses as recognition molecules. Nevertheless, HLA gene expression patterns among diverse cell types within a specific organ, like the skin, have yet to be thoroughly investigated, with stromal cells attracting much less attention than immune cells. To illustrate HLA expression profiles across different cell types in the skin, we performed single-cell RNA sequencing (scRNA-seq) analyses on skin datasets, covering adult and fetal skin, and hair follicles as the skin appendages. We revealed the variation in HLA expression between different skin populations by examining normal adult skin datasets. Moreover, we evaluated the potential immunogenicity of multiple skin populations based on the expression of classical HLA class I genes, which were well represented in all cell types. Furthermore, we generated scRNA-seq data of developing skin from fetuses of 15 post conception weeks (PCW), 17 PCW, and 22 PCW, delineating the dynamic expression of HLA genes with cell type-dependent variation among various cell types during development. Notably, the pseudotime trajectory analysis unraveled the significant variance in HLA genes during the evolution of vascular endothelial cells. Moreover, we uncovered the immune-privileged properties of hair follicles at single-cell resolution. Our study presents a comprehensive single-cell transcriptomic landscape of HLA genes in the skin, which provides new insights into variation in HLA molecules and offers a clue for allogeneic skin transplantation.

Elucidating the physiological and pathological characteristics of preterm birth is critical to the development of effective prediction and intervention strategies. Here, we present a nested case control study on 51 spontaneous preterm birth (sPTB) and 70 women who delivered at term. Systems-level analysis revealed bacterial compositions and functional differences between two distinct pregnancy outcomes. As expected, the vaginal environment with preterm birth was dominated by a more complex bacteria interaction network, and these interactions frequently exhibited opposite effects on different pregnancy outcomes. Furthermore, key species and combinations were identified to construct preterm birth prediction model. The final model contained three features generated from six bacteria (A. christensenii and L. crispatus; B. breve and S. anginosus; P. timonensis and L. fermentum) (AUROC = 0.942 for independent test). The AUROC value was 0.965 when white blood cell (WBC) and neutrophil (NEU) data were included. Collectively, our study provided a comprehensive characterization of the vaginal microbiome and revealed the potential utilization of bacteria in predicting the risk of preterm birth.

Background Physiological glycated hemoglobin (HbA1c) values in each trimester are not well defined. This study aimed to determine trimester-specific reference intervals for HbA1c levels in non-diabetic pregnant women in China. Methods In this cross-sectional study, 5,042 Chinese pregnant women from 6 to 41 weeks of gestation were screened. An inclusion of 4,134 non-diabetic women was made to determine the reference intervals, they were divided into three trimesters: trimester 1 (T1), 6 weeks to 13 weeks + 6 days, trimester 2 (T2), 14 weeks to 27 weeks + 6 days, and trimester 3 (T3), 28 weeks to 41 weeks + 6 days. A total of 4,134 women (T1 n = 760, T2 n = 1,953, and T3 n = 1,421) provided blood samples which were analyzed for HbA1c concentrations. HbA1c was measured using high-performance liquid chromatography. The median and percentile (2.5th to 97.5th) for the HbA1c reference intervals were calculated for each trimester. Results In total, 8,732 HbA1c measurements were taken. Reference intervals for HbA1c expressed as median and percentile (2.5th to 97.5th) for each trimester were: T1: 4.7 (4.0–5.5%), T2: 4.5 (3.9–5.3%), and T3: 4.8 (4.1–5.7%) respectively. The HbA1c levels were significantly lower in the second trimester compared to those in the first trimester (p < 0.0001), and higher in the third trimester compared to the second trimester (p < 0.0001). Conclusions The reference intervals for HbA1c levels were 3.9–5.7% with upper limits of 5.5% in the first trimester, 5.3% in the second trimester, and 5.7% in the third trimester. These findings highlight the importance of considering trimester-specific reference intervals for HbA1c in non-diabetic pregnant women to promote maternal and fetal health.

目的 评价加速康复外科(ERAS)干预对剖宫产术后功能恢复的影响.方法 收集2021年9月1日至2022年9月1日在深圳市龙岗区妇幼保健院产科行剖宫产分娩的194例产妇为研究对象,采用前瞻性、随机单盲的研究方法,使用随机数表法将产妇随机分为快速康复组(ERAS组,96例)和常规组(98例).ERAS组给予跨越术前、术中和术后的综合干预措施;常规组给予常规围手术期干预措施.观察剖宫产围手术期的ERAS措施对产妇疼痛视觉模拟评分(VAS)、术后阿片类药物使用情况、胃肠道恢复情况、膀胱功能、首次下床活动时间、24 h阴道出血量等的影响.结果 ERAS组和常规组基线资料比较均无显著性差异(P＞0.05).ERAS组产妇剖宫产术后回病房0 h的VAS与常规组无显著性差异(P=0.546),但术后回病房4 h、12 h、16 h和24 h的VAS显著低于常规组(P均＜0.05).ERAS组术后需要联合使用舒芬太尼和地佐辛的比率显著低于常规组(29.2％vs.46.9％,P＜0.05).ERAS组术后首次进食流质时间[(2.6±1.1)h vs.(4.3±2.3)h]、进食半流质时间[(7.5±6.8)h vs.(20.5±15.0)h]、进食普食时间[(35.1±15.7)h vs.(41.4±13.2)h]、拔尿管时间[(9.8±5.1)h vs.(23.5±4.5)h]、拔尿管后首次排尿时间[(12.9±5.4)h vs.(25.9±4.3)h]及首次下床时间[(13.8±6.0)h vs.(26.8±6.7)h]均显著短于常规组(P＜0.01).两组的首次肛门排气时间及产后24h出血量均无显著性差异(P＞0.05).结论 ERAS干预应用于剖宫产孕妇围手术期,能够减轻产妇疼痛,具有阿片节省效应,还能有效缩短孕产妇空腹时间,促进膀胱功能恢复和产后尽早活动.

目的 探讨以问题为基础的学习(PBL)联合临床技能多站式考试(OSCE)教学策略在高质量产科模拟教学中的应用效果.方法 选取2016级产科1班和2班为研究对象,按照实施教学管理方案不同,将产科1班作为试验组,实施PBL联合OSCE教学策略,产科2班作为对照组,实施常规教学指导,每组30名.比较两组教学效果和专业OSCE考试成绩.结果 试验组在提高分析及解决能力、激发学习兴趣、促进内容记忆、提高临床思维能力、加强团队协作及提高医患沟通能力占比均高于对照组,差异有统计学意义(P＜0.05).试验组病史采集、病历书写、产前检查、临床技能操作及产科手术操作评分均高于对照组,差异有统计学意义(P＜0.05).结论 产科模拟教学指导过程中,以PBL联合OSCE教学策略指导,能够提高产科模拟教学质量.

目的 探讨孕妇BMI及血脂指标与妊娠期高血压、子痫前期的相关性,分析其对妊娠结局的影响.方法 选取2019年6月1日-2020年1月31日于某院分娩的妊娠期高血压疾病产妇115例作为研究组,其中妊娠期高血压63例,子痫前期52例;健康产妇115例,作为对照组.比较2组孕产妇BMI及血脂指标差异,并进行多因素分析.比较2组不良妊娠结局的发生率.结果 孕前、孕16周、孕37周BMI及孕16周TC、TG、HDL、LDL、孕37周TC、TG均是影响孕产妇妊娠期高血压及子痫前期发生的独立危险因素(P<0.05).研究组胎儿窘迫、低体重儿发生率分别为4.35％、6.96％,显著高于对照组(P<0.05).结论 BMI及血脂异常与妊娠期高血压及子痫前期发生具有相关性,可导致不良妊娠结局发生,应对其进行干预,改善母婴结局.

目的:研究快速康复途径(ERAS)应用于剖宫产围手术期对母婴结局的影响.方法:选择我院收治剖宫产孕妇240例作为研究对象,病例均选自2020年7月至2021年8月.采用单盲、随机分组原则将孕妇分成两组,对照组120例给予常规手术干预方法,试验组120例给予ERAS临床干预(快速康复组).比较术中出血量、胃肠功能恢复时间、平均住院时间、住院平均费用;同时比较两组产后抑郁评分、疼痛耐受情况,以及术后并发症.结果:试验组术中出血量少于对照组,术后肠鸣音恢复、术后排气时间短于对照组,平均住院时间、住院费用均少于对照组,差异有统计学意义(P<0.05);试验组孕妇产后抑郁SDS评分与疼痛VAS评分均少于对照组,差异有统计学意义(P<0.05);试验组术后并发症发生率1.67％低于对照组7.50％,差异有统计学意义(P<0.05).结论:在剖宫产围手术期临床干预中应用ERAS快速康复途径可改善母婴结局,值得应用.

目的 研究apelin受体的内源性配体(APELA)基因cg02779075位点在6项胎盘全基因组甲基化中与子痫前期关联的甲基化改变.方法 系统回顾APELA基因cg02779075位点在6项胎盘全基因组甲基化中与子痫前期关联的甲基化改变.此外,回顾性采集医院2019年1-2019年12月采集获取的47例子痫前期以及50例正常妊娠孕妇胎盘组织样本.分析两组母婴基线资料以及CpG稳点甲基化水平的差异.结果 6项研究中cg02779075位点于子痫前期胎盘中DNA甲基化水平显著下调,其中4项研究结果存在明显差异(均为P＜0.05).异质性检验分析结果显示:各文献之间存在明显异质性(I2=0.64,P=0.016),通过随机效应模型计算合并SMD值为-1.16,较各单项文献更为明显,但尚未达到全基因组显著水平.子痫前期孕周、产妇收缩压、产妇舒张压均高于正常妊娠,且胎盘重量、新生儿出生体质量均低于正常妊娠(均为P＜0.05).子痫前期APELA基因 CpG1～CpG4位点甲基化水平分别为(0.12±0.05)、(0.07±0.02)、(0.22±0.07)、(0.43±0.12),均明显低于正常妊娠的(0.22±0.08)、(0.18±0.04)、(0.30±0.10)、(0.51±0.16),差异有统计学意义(均为P＜0.05).结论 子痫前期产妇胎盘中APELA基因cg02779075位点甲基化调控异常,值得临床重点关注.

Mesenchymal stromal cells (MSCs) show potential for treating preclinical models of newborn bronchopulmonary dysplasia (BPD), but studies of their therapeutic effectiveness have had mixed results, in part due to the use of different media supplements for MSCs expansion in vitro. The current study sought to identify an optimal culture supplement of umbilical cord-derived MSCs (UC-MSCs) for BPD therapy. In this study, we found that UC-MSCs cultured with human platelet lysate (hPL-UCMSCs) were maintained a small size from Passage 1 (P1) to P10, while UC-MSCs cultured with fetal bovine serum (FBS-UCMSCs) became wide and flat. Furthermore, hPL was associated with lower levels of senescence in UC-MSCs during in vitro expansion compared with FBS, as indicated by the results of β-galactosidase staining and measures of senescence-related genes (CDKN2A, CDKN1A, and mTOR). In addition, hPL enhanced the proliferation and cell viability of the UC-MSCs and reduced their doubling time in vitro. Compared with FBS-UCMSCs, hPL-UCMSCs have a greater potential to differentiate into osteocytes and chondrocytes. Moreover, using hPL resulted in greater expression of Nestin and specific paracrine factors (VEGF, TGF-β1, FGF2, IL-8, and IL-6) in UC-MSCs compared to using FBS. Critically, we also found that hPL-UCMSCs are more effective than FBS-UCMSCs for the treatment of BPD in a rat model, with hPL leading to improvements in survival rate, lung architecture and fibrosis, and lung capillary density. Finally, qPCR of rat lung mRNA demonstrated that hPL-UCMSCs had lower expression levels of inflammatory factors (TNF-α and IL-1β) and a key chemokine (MCP-1) at postnatal day 10, and there was significant reduction of CD68+ macrophages in lung tissue after hPL-UCMSCs transplantation. Altogether, our findings suggest that hPL is an optimal culture supplement for UC-MSCs expansion in vitro, and that hPL-UCMSCs promote lung repair in rat BPD disease.

AIMS Currently, there is no reliable method to effectively predict and diagnose early-onset preeclampsia (EOPE). microRNAs (miRs) are promising biomarkers for EOPE. This study investigated the role of miR-320a in EOPE. METHODS Expressions of miR-320a and insulin-like growth factor-1 receptor (IGF-1R) in serum of EOPE patients and normal pregnant women were detected. The clinical diagnostic efficacy of miR-320a and IGF-1R for EOPE was analyzed using receiver operating characteristic curve. The correlation between miR-320a expression and EOPE clinical indicators [mean arterial pressure (MAP), 24-h urinary protein excretion, serum creatinine (SCR), uric acid (UA), albumin (ALB) and platelet count] was analyzed. The correlation and binding relationship between miR-320a and IGF-1R was predicted and verified. RESULTS miR-320a was upregulated, and IGF-1R was downregulated in EOPE patients with their differential expressions more obvious in severe EOPE than mild EOPE. miR-320a and IGF-1R possessed potent clinical diagnostic efficacy for EOPE. miR-320a expression showed a positive correlation with MAP, 24-h urinary protein excretion, UA and SCR levels, and a negative correlation with ALB level and platelet count in EOPE patients. Moreover, miR-320a targeted IGF-1R. CONCLUSION We demonstrated that miR-320a was aberrantly elevated in EOPE and showed powerful clinical diagnostic efficacy for EOPE, which may be achieved by directly targeting IGF-1R. This study provided great reference values for EOPE early diagnosis and novel targets for EOPE treatment.

胎母输血综合征(fetomaternal hemorrhage,FMH)是指一定量的胎儿血液经过已经受到损伤的胎盘绒毛进入母体中,导致胎儿失血和母亲体内出现溶血性反应的一种临床症状,是胎儿非免疫性水肿不可忽视的原因之一[1-2].在妊娠与分娩过程中,有体积程度的胎儿血液融入到母体当中,通常是5～30 mL不等,但由于孕妇的血容量比较多,胎儿血液进入到母体中很快被稀释,因此不会影响到血型的鉴定[3].但当胎儿血液体积较多,红细胞数量达到一定比例的时候,就会出现胎儿贫血的情况[4].本研究拟将2019年3月10日1例诊断为胎母输血综合征孕妇及其新生儿状态汇报如下.

胎盘间叶发育不良(PMD)在临床上较为罕见,其特征是干绒毛囊性扩张和囊泡形成、胎盘肥大和血管异常等,常伴有胎儿生长发育受限(FGR)、死胎、Beckwith-Wiedemann综合征,以及一些染色体异常等,临床上需与葡萄胎加以鉴别.本文报道1例母婴结局良好的PMD患者,并针对已知的PMD发病机制,对PMD临床诊疗的手段进行文献复习及讨论,以期为临床上PMD患者确定终止妊娠时机和分娩方式选择以及优化产前筛查等提供一定参考.

目的 :探讨在妇产科临床实习带教中采取PBL联合标准化病人教学的效果.方法 :选取15名妇产科实习生作为研究对象,均采取PBL结合标准化病人教学的带教方式,对实习3个月的带教效果进行评价.结果 :实习生对带教工作的较满意,在各调查项目上均给予正向的评价.结论 :在妇产科临床实习带教中采取PBL结合标准化病人教学方式,可取到满意的带教效果,值得推广.

目的 观察Genistein对大鼠卵巢颗粒细胞cAMP反应元件结合蛋白(CREB)基因表达的影响及其与雌激素受体(ER)的关系.方法 分离大鼠卵巢颗粒细胞进行培养,分别给予Genistein(0.1、1、5、10、100μmol/L)及ER阻断剂ICI182,780(1μmol/L)处理24 h后,采用RT-PCR检测CREB mRNA的表达.结果 1、5和10μmol/L Genistein组CREB mRNA表达显著高于空白对照组(P<0.05或P<0.01).细胞预先加入ER阻断剂ICI182,780处理30 min后,再加入1、10μmol/L Genistein处理24 h组,CREB mRNA表达与1、10μmol/L Genistein组比较,差异均无统计学意义(P>0.05).结论 1～10μmol/L的Genistein可上调大鼠卵巢颗粒细胞CREB基因的表达,但可能并非通过ER介导.