The blood-testis barrier (BTB), a unique structure established through intercellular connections of Sertoli cells, establishes a protective microenvironment for spermatogenesis and male fertility. Cadmium (Cd), known for its toxicity, is ubiquitously present in the environment. Here, our findings revealed that Cd exposure compromises BTB integrity, as demonstrated by decreased expression of BTB-associated proteins and elevated Dsignal/Dradius values. Mechanistically, we demonstrated that activation of the CXCL2/CXCR2 axis contributes to Cd-induced BTB impairment, as evidenced by experiments using a CXCR2 inhibition model. As key BTB components, Sertoli cells rely on autophagy to maintain their physiological functions. However, the specific role and mechanism of Sertoli cell autophagy in Cd-induced BTB damage remain unknown. Notably, our results showed that autophagy inhibition aggravated the Cd-induced BTB disruption and testicular CXCL2/CXCR2 axis activation in mice, whereas autophagy activation alleviates Cd-evoked BTB disruption and testicular CXCL2/CXCR2 axis activation. Further verification by Sertoli cell specific Atg5 knockout mouse model showed that the autophagy suppression exacerbated Cd-induced BTB disruption and upregulated the expression of CXCL2. Collectively, our finding points out that ATG5-dependent autophagy in Sertoli cells protects against Cd-induced BTB disruption via perturbing CXCL2/CXCR2 axis. Our study not only reveals a novel molecular mechanism underlying Cd-induced reproductive toxicity but also provides potential therapeutic targets for male infertility intervention.

Objectives This study aimed to investigate copy number variations (CNVs) and potential candidate genes associated with fetal congenital heart disease (CHD) and to compare the prevalence of CNVs among different CHD subtypes. Methods A retrospective analysis was performed on 391 fetuses diagnosed with CHD between 2019 and 2023. 391 fetuses with case were divided into three groups: isolated CHD (Group 1), complex CHD (Group 2), and CHD with extracardiac anomalies (Group 3). Amniocentesis was performed for all pregnant women, with both karyotyping and CMA conducted. Gene Ontology (GO) annotation and KEGG pathway analyses were conducted for isolated and complex CHD cases. Results CMA and karyotype detected total abnormalities in 22 % of all CHD fetuses, including a chromosomal aneuploidy rate of 7.2 %, a pathogenic CNV (pCNV) rate of 6.1 %. The overall detection rates for Groups 1, 2, and 3 were 11.6 %, 12.5 %, and 50 %, respectively. Group 3 exhibited significantly higher rates of chromosomal aneuploidy (23.7 %) and pCNV (17.8 %) compared to Groups 1 and 2 (p < 0.001 ). No significant differences in maternal age were observed among the three CHD groups. KEGG pathway analysis identified the top three enriched pathways for complex CHD were nucleocytoplasmic transport, cell adhesion molecules, and the mRNA surveillance pathway. Conclusions The rates of chromosomal aneuploidy and CNV abnormalities in CHD cases with extracardiac anomalies were significantly higher than in the other two groups. Maternal age was not associated with the chromosomal abnormalities observed in CHD cases. KEGG pathway analysis indicated more intricate molecular pathways in complex CHD.

To evaluate the application of targeted amplicon sequencing (TA-seq)—a method based on multiplex PCR and high-throughput sequencing—for the prenatal detection of uniparental disomy (UPD)-related imprinting disorders (ImpDis). This retrospective study included 370 samples suspected of UPD from 42 hospitals across China. Of these, 294 samples were successfully tested by TA-seq, and methylation multiplex ligation-dependent probe amplification (MS-MLPA) being regarded as the reference method for methylation-based detection of imprinting disorders. TA-seq identified 36 positives and 258 negatives, of which 30 positives and 255 negatives were consistent with the findings from MS-MLPA. The sensitivity, specificity, positive predictive value, and negative predictive value of TA-seq were 90.9

OBJECTIVES:Chromosomal abnormalities are the most common cause of spontaneous abortion (SA). This study aims to analyze the association between SA and chromosomal abnormalities in products of conception, and to compare the impact of different pregnancy modes and different numbers of previous abortions on chromosomal abnormalities, providing clinical consulting references. METHODS:A total of 1 345 SA patients treated at the Affiliated Women's Hospital of Jiangnan University (Wuxi Maternity and Child Health Care Hospital) between January 2019 and December 2023 were enrolled. According to the mode of conception, patients were divided into 2 groups: a spontaneous pregnancy group (S group, n=1242) and an assisted reproductive technology (ART)-conceived group (ART group, n=103). Based on the number of miscarriages, the S group was further subdivided into a spontaneous sporadic abortion group (S-1 group, n=780) and a spontaneous recurrent abortion group (S-2 group, n=462); the ART group was subdivided into an ART sporadic abortion group (ART-1 group, n=68) and an ART recurrent abortion group (ART-2 group, n=35). Chromosomal microarray analysis (CMA) was performed on products of conception. RESULTS:The incidence of numerical chromosomal abnormalities was 56.79% (443/780) in the S-1 group and 52.38% (242/462) in the S-2 group, while the incidence of structural abnormalities was 4.36% (34/780) and 7.36% (34/462), respectively. There was a statistically significant difference in structural abnormalities between the 2 groups (P<0.05). Among the spontaneous pregnancy SA cases, the incidence of numerical abnormalities decreased with increasing numbers of miscarriages, and was significantly lower in the group with ≥4 miscarriages compared to those with 1 or 2 miscarriages (both P<0.05). The incidence of structural abnormalities in groups with 1, 2, 3, and ≥4 miscarriages was 3.46%, 5.65%, 5.88%, and 4.35%, respectively, with no statistically significant differences among groups (all P>0.05). The incidence of pathogenic copy number variants (pCNVs) plus likely pathogenic copy number variants (LP-CNVs) gradually increases in the group with 1-3 miscarriages, and there was a statistically significant difference between the group with 1 miscarriage and the group with 2 miscarriages (P<0.05). In the ART group, the incidence of numerical abnormalities was 47.06% (32/68) in ART-1 and 37.14% (13/35) in ART-2, while structural abnormalities occurred in 2.94% (2/68) and 11.43% (4/35), respectively, with no significant differences between the groups (both P>0.05). There were no statistically significant differences in the incidence of numerical or structural abnormalities between the S-1 and ART-1 groups, or between the S-2 and ART-2 groups (all P>0.05). CONCLUSIONS:Chromosomal numerical and structural abnormalities are common in SA patients from both spontaneous and ART-conceived pregnancies. Attention should be paid to patients with recurrent miscarriage in genetic investigation.

INTRODUCTION:Recurrent spontaneous abortion (RSA) is associated with maternal-fetal interface dysfunction, particularly abnormal trophoblast invasion and proliferation. However, our understanding of the cause of RSA remains limited. METHODS:Plasma Trp and Kyn levels were measured in two groups using enzyme-linked immunosorbent assay. Immunofluorescence and western blot analyses were employed to evaluate the expression of IDO1, VEGFA, and proteins associated with epithelial-mesenchymal transition (EMT) in villous and decidual tissues from patients with RSA. The effects of Tryptophan (Trp) and IDO1-driven Trp-Kynurenine (Kyn) metabolism on trophoblast proliferation, migration, EMT, and angiogenesis were investigated in the HTR-8/SVneo cell line using wound healing, transwell migration, quantitative real-time PCR (RT-qPCR), Western blotting, and tube formation assays. RNA sequencing (RNA-seq) identified differentially expressed genes in cells treated with 500 μM exogenous L-Trp. RESULTS:RSA patients exhibited elevated plasma Trp levels and significantly reduced Kyn levels, indicating decreased IDO1 activity (as assessed by the Kyn/Trp ratio) compared to controls. IDO1, EMT-related proteins, and VEGFA were downregulated in RSA patient tissues. In vitro, L-Trp enhanced trophoblast migration, invasion, EMT, and microvasculature formation via IDO1 activation. The reduced functional capabilities induced by the IDO1 antagonist 1-MT (500 μM) were rescued by Kyn (300 μM). RNA-seq revealed that L-Trp upregulation modulates trophoblast gene expression and functional pathways associated with amino acid metabolism, angiogenesis, and vasculature development. DISCUSSION:Our study reveals a novel molecular mechanism by which Trp metabolism regulates HTR-8 cell function, suggesting that modulating IDO1 activity may represent a therapeutic strategy to improve trophoblast function and pregnancy outcomes in RSA.

AIM:There is limited and conflicting evidence available regarding the correlation between maternal vitamin D status and childhood overweight and body mass index (BMI). The aim of this study was to investigate the following: (1) potential association between maternal 25-hydroxyvitamin D (25(OH)D) levels and newborn growth status; (2) relationship between maternal 25OHD levels and BMI and the risk of overweight with preschoolers being overweight. METHODS:A cohort of 3213 eligible singleton mother-infant pairs were used to investigate the possible associations between maternal 25(OH)D levels and fetal growth status. Data of 1767 available singleton mother-infant pairs and 6-year-old preschoolers was applied to analyze the potential correlations between maternal 25(OH)D status and risk of childhood overweight. RESULTS:Compared with sufficient 25(OH)D in pregnancy group (≥75 nmol/L), there were no correlations between the maternal 25(OH)D deficiency (<50 nmol/L) and large gestational age (LGA) (p = 0.465), small gestational age (SGA) (p = 0.607), lower birth weight (LBW) (p = 0.725) or fetal macrosomia (p = 0.535). Moreover, no significant associations between insufficient maternal 25(OH)D (50-75 nmol/L) and LGA (p = 0.505), SGA (p = 0.816), LBW (p = 0.816), or fetal macrosomia (p = 0.413) were observed. We found statistically significant disparities between the fetal birth weight and height (p < 0.001), weight (p < 0.001), head circumference (p = 0.001) of 6-years preschooler. No significant associations were found between the maternal 25(OH)D levels and BMI and risk of overweight at 6-year-old preschoolers. CONCLUSION:There were no apparent correlation found between maternal 25(OH)D concentrations and fetal birth status. There was no evidence found to suggest the effect of maternal 25(OH)D level on overweight at 6-year-old preschoolers.

Infertility caused by lipopolysaccharide (LPS) exposure due to infection is endangering male fertility worldwide, but the mechanism remains unclear. The blood-testis barrier (BTB) is essential for maintaining spermatogenesis and male fertility. In the present study, we showed that LPS (5.0 mg/kg) treatment markedly down-regulated the expression of BTB-related proteins, expanded the biotin penetration distance and caused histopathological injury in seminiferous tubules in mouse testes. Notably, testicular macrophage M1 polarization induced by LPS seems to be related to BTB damage, which was well confirmed by co-culture of RAW264.7 and TM4 cells in vitro. Interestingly, a low-dose LPS (0.1 mg/kg) pretreatment attenuated down-regulation of BTB-related proteins expression and histopathological injury and shorten biotin penetration distance in seminiferous tubules caused by LPS. Correspondingly, a low-dose LPS pretreatment suppresses testicular macrophage M1 polarization induced by LPS in mouse testes. Further experiments revealed that histone deacetylase 5 (HDAC5) was markedly down-regulated at 2 h and slightly down-regulated at 8 h, but up-regulated at 24 h in mouse testes after LPS treatment. Additionally, low-dose LPS pretreatment against the down-regulation of HDAC5 protein caused by LPS treatment. Notably, the suppressed testicular macrophage M1 polarization by low-dose LPS pretreatment was broken by BRD4354, a specific inhibitor of HDAC5 in vitro. These results suggest suppressed testicular macrophage M1 polarization by HDAC5 enforces insensitivity to LPS-elicited BTB damage.

Cadmium (Cd) is a widely distributed typical environmental pollutant and one of the most toxic heavy metals. It is well-known that environmental Cd causes testicular damage by inducing classic types of cell death such as cell apoptosis and necrosis. However, as a new type of cell death, the role and mechanism of pyroptosis in Cd-induced testicular injury remain unclear. In the current study, we used environmental Cd to generate a murine model with testicular injury and AIM2-dependent pyroptosis. Based on the model, we found that increased cytoplasmic mitochondrial DNA (mtDNA), activated mitochondrial proteostasis stress occurred in Cd-exposed testes. We used ethidium bromide to generate mtDNA-deficient testicular germ cells and further confirmed that increased cytoplasmic mtDNA promoted AIM2-dependent pyroptosis in Cd-exposed cells. Uracil-DNA glycosylase UNG1 overexpression indicated that environmental Cd blocked UNG-dependent repairment of damaged mtDNA to drive the process in which mtDNA releases to cytoplasm in the cells. Interestingly, we found that environmental Cd activated mitochondrial proteostasis stress by up-regulating protein expression of LONP1 in testes. Testicular specific LONP1-knockdown significantly reversed Cd-induced UNG1 protein degradation and AIM2-dependent pyroptosis in mouse testes. In addition, environmental Cd significantly enhanced the m6A modification of Lonp1 mRNA and its stability in testicular germ cells. Knockdown of IGF2BP1, a reader of m6A modification, reversed Cd-induced upregulation of LONP1 protein expression and pyroptosis activation in testicular germ cells. Collectively, environmental Cd induces m6A modification of Lonp1 mRNA to activate mitochondrial proteostasis stress, increase cytoplasmic mtDNA content, and trigger AIM2-dependent pyroptosis in mouse testes. These findings suggest that mitochondrial proteostasis stress is a potential target for the prevention of testicular injury.

Abstract Objective To evaluate the value of chromosomal microarray analysis (CMA) in the prenatal diagnosis of high-risk pregnancies.Methods A total of 3459 pregnant women admitted to the Wuxi Maternal and Child Health Hospital between June 2020 and August 2022 were selected for this study. Both G-banding karyotype analysis and CMA were offered to all patients who underwent invasive prenatal diagnosis. Short tandem repeat (STR) analysis was performed to eliminate maternal contamination for interpretation.Results Chromosomal aberrations, including aneuploidies or triploid and mosaic aberrant karyotypes and copy number variants (CNVs) ≥ 5Mb, were detected by both G-banding karyotyping and CMA in 174 (5.0%) cases. A total of 326 (9.4%) cases with normal karyotypes were reported as CNVs in CMA, including 71 (2.1%) cases with pathogenic and likely pathogenic CNVs and 217(6.3%) cases with variants of uncertain significance (VOUS). On the other hand, 11 inversions, 23 balanced translocations, and 22 other chromosomal rearrangements were detected by karyotyping with normal CMA results.Conclusion The top 3 detection rates of different indications by CMA or karyotyping were 43.5% for NIPT high risk, 17.5% for abnormal ultrasound, and 17.7% for other indications. CMA is an effective diagnostic tool for high-risk pregnancies in perinatal medicine.

Cadmium (Cd), one of the most common contaminants in diet and drinking water, impairs testicular germ cell development and spermatogenesis. Autophagy is essential for maintaining Sertoli cell function and Sertoli-germ cell communication. However, the role of Sertoli cell autophagy in Cd-caused spermatogenesis disorder remains unclear. Here, the mice of autophagy-related gene 5 (Atg5) knockouts in Sertoli cells were used to investigate the effect of autophagy deficiency on Cd-impaired spermatogenesis and its underlying mechanisms. Results showed that Sertoli cell-specific knockout of Atg5 exacerbated Cd-reduced sperm count and MVH (a specific marker for testicular germ cells) level in mice. Additionally, Sertoli cell Atg5 deficiency reduced the number of spermato-cytes and decreased the level of meiosis-related proteins (SYCP3 and STRA8) in Cd-treated mouse testes. Loss of Atg5 in Sertoli cell exacerbated Cd-reduced the level of retinoic acid (RA) and retinal dehydrogenase (ALDH1A1 and ALDH1A) in mouse testes. Meanwhile, we found that the level of transcription factor WT1 was significantly downregulated in Atg5-/- plus Cd-treated testes. Further experiments showed that Wt1 overexpression restored Cd-decreased the levels of ALDH1A1 in Sertoli cells. Collectively, the above data suggest that knockout of Atg5 in Sertoli cell enhances the susceptibility of Cd-impaired testicular spermatogenesis. These findings provide new insights into autophagy of Sertoli cell preventing environmental toxicants-impaired testicular spermatogenesis.

The supplementation of multiple micronutrients throughout pregnancy can reduce the risk of adverse birth outcomes and various diseases in children. However, the long-term effect of maternal multiple micronutrient levels in the second trimester on the overall development of preschoolers remains unknown. Therefore, 1017 singleton mother–infant pairs and 6-year-old preschoolers were recruited based on the China-Wuxi Birth Cohort Study. Meanwhile, information on the demographic characteristics of pregnant women and preschoolers, maternal copper, calcium, iron, magnesium, and zinc levels in whole blood during the second trimester, and neonatal outcomes, were collected. We aimed to investigate the long-term impact of maternal copper, calcium, iron, magnesium, and zinc levels in the second trimester on mild thinness among 6-year-old preschoolers, and the modifying effect of small for gestational age (SGA), within the Chinese population. Multiple logistic regression models revealed that high-level maternal iron in the second trimester reduced the risk of mild thinness [adjusted OR: 0.46 (95% CI: 0.26, 0.80)] among 6-year-old preschoolers. However, no significant association was found for the remaining four maternal essential metal elements. Additionally, the restricted cubic spline function showed that the risk of mild thinness decreased when maternal iron concentration exceeded 7.47 mmol/L in whole blood during the second trimester. Furthermore, subgroup analysis indicated that the long-term protective effect of high-level maternal iron on mild thinness was only observed in SGA infants. Summarily, high-level maternal iron in the second trimester distinctly lowers the risk of mild thinness among 6-year-old preschoolers, especially in preschoolers with birth outcomes of SGA. Our findings offer evidence for the implementation of iron supplementation in the second trimester as a preventive measure against mild thinness in children.

Objective: To evaluate the diagnostic value of the BACs-on-Beads (BoBs) assay for the rapid diagnosis of common aneuploidies and microdeletions. Methods: A total of 4961 pregnant women admitted to the Wuxi Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University from January 2017 to March 2019 were enrolled. BoBs assay and conventional karyotyping were applied to detect amniotic fluid samples with various indications for prenatal diagnosis. Chromosomal microarray analysis (CMA) and maternal cell contamination (MCC) tests were used for further validation. Results: The overall abnormality detection rates (BoBs associated with karyotyping) were 4.25% (211/4961). The prenatal diagnosis success rate of karyotyping was 99.4% (4933/4961), compared to 100% (4961/4961) using the BoBs assays. The BoBs assay was similar to karyotyping for the detection of trisomy 21 (1.01%, 50/4961), trisomy 18 (0.40%, 20/4961), trisomy 13 (0.04%, 2/4961), and sex chromosomal aneuploidies (0.15%, 12/4961). The BoBs assay also identified sex chromosomal microduplications/microdeletions (1.73%, 86/4961), 22q11.2 microdeletions/microduplications (0.1%, 5/4961), and Cri du Chat syndrome (0.02%, 1/4961) which were missed by karyotyping. The sensitivity for the detection of numerical chromosomal abnormalities of the BoBs assay and karyotyping analysis was 100% (95/95, 95% CI: 1.0-1.0) and 98.9% (94/95, 95% CI: 0.969-1.010), respectively. The sensitivity of detecting structural chromosomal abnormalities in the BoBs assay was significantly higher than those of karyotyping (79.3%, 92/116, 95% CI: 0.718-0.868) versus 21.6% (25/116, 95% CI: 0.140-0.291) (p < .01). Conclusions: The BoBs assay is a reliable and rapid test for the detection of common aneuploidies and nine microdeletion syndromes with high sensitivity and accuracy in prenatal diagnosis. The assay can compensate for the limitations of karyotyping analysis.

Fetal chromosomal abnormalities are a common cause of spontaneous abortion. The present study investigated the association between fetal chromosomal abnormalities and the frequency of spontaneous abortions to enable clinicians to provide more informed genetic counseling. A total of 182 patients with a history of spontaneous abortions were recruited from July 2015 to August 2017. G-banding cytogenetic analysis and novel high-throughput ligation-dependent probe amplification (HLPA) techniques were performed on conception in all 182 patients to detect chromosomal abnormalities. Low-coverage whole-genome sequencing (WGS) was performed in 74 patients to detect copy number variations (CNVs). There were no significant differences in the incidence of karyotype abnormalities between patients with sporadic miscarriages (48.0%; SM group) and patients suffering recurrent spontaneous abortions (44.8%; RSA group). The maternal age was markedly higher in patients with 3 miscarriages. WGS indicated that the incidence of pathogenic CNVs in the RSA group was higher than that in the SM group, but the difference was not significant. In conclusion, a high incidence of karyotype abnormalities and pathogenic CNVs was observed in patients with spontaneous abortion. However, no association between fetal chromosomal abnormalities and the number of spontaneous abortions was observed. HLPA assays may be used as an alternative method for fetal karyotype analysis and determination of CNVs in patients with SM and RSA.

Recurrent spontaneous abortions (RSA) are defined as aborting three or more times within 20 gestational weeks with the same sexual partner. The occurrence of RSA exhibits an upward trend in modern society. The NACHT, LRR and PYD domains‑containing protein 3 (NLRP3) inflammasome, which is an important component of innate immunity, serves a role in the immune response and in disease occurrence. In the present study, it was demonstrated that the disordered regulation of the NLRP3 inflammasome may induce the occurrence of RSA. The results of the present study demonstrated that caspase‑1 activity, interleukin (IL)‑1β and IL‑18 were upregulated in patients with RSA compared with healthy controls. Further investigation was performed to elucidate the mechanism of activation of the NLRP3 inflammasome in patients with RSA. The inhibition of the NLRP3 inflammasome in a RSA mouse model was able to decrease the rate of abortions. Finally, the present study demonstrated that the activated NLRP3 inflammasome was involved in the pathogenesis of RSA through regulation of the Th17 and regulatory T cell imbalance. The present study provides a potential future therapeutic target for RSA via the NLRP3 inflammasome.

BACKGROUND:Non-invasive prenatal testing (NIPT) is routinely used in clinical practice for fetal trisomy screening, but low total cfDNA content and low fetal fraction (LFF) are two factors that affect the detection rate. Samples with low total cfDNA or LFF usually end up with "no-call" results, followed by the blood redraw and re-testing, which is inconvenient for pregnant women and clinicians.METHODS:We created mock trisomy 21 (T21) samples to investigate the effects of low total cfDNA with low LFF and possible solutions to increase their detection rate.RESULTS:Samples with low total cfDNA resulted in the decreased unique reads number and increased duplication rate. Abnormal correlations between library concentration and raw reads number and the coverage fluctuation value, ZsdNorm, were also discovered, suggesting that low total cfDNA could lead to the overestimation of the library concentration. Additionally, a non-reference-based derivative value method (DV method) was evaluated and the data demonstrated that the detection sensitivity of trisomy 21 was increased from 33.33% (6/18) to 94.44% (17/18) in samples with 5% fetal fraction comparing with the z-score approach, whereas for LFF (3.5%) group, the performance was raised from 0% to 35.29% (6/17).CONCLUSION:Low total cfDNA has significant impacts on NIPT performance by altering sequencing quality. The non-reference-based DV method could increase the T21 detection rate in samples with limited cfDNA content and 5% fetal fraction, but it was not as effective for those with LFF.

目的:分析自然流产患者流产组织染色体数目和拷贝数异常的发生率与流产次数之间的关系,为临床医师提供咨询指导意见.方法:选择2014年7月-2016年12月本院就诊的孕14周内自然流产患者共173例,根据流产次数分4组:A组(偶发流产组,仅发生1次自然流产者)45例,B组(自然流产2次)86例,C组(自然流产3次)32例,D组(自然流产≥4次)10例,对绒毛组织采用细胞培养G显带分析技术、多重拷贝数变异检测技术、高通量基因测序技术等3种方法进行染色体检查.结果:173例自然流产患者绒毛染色体培养成功137例(79.2％),结合3种技术的检查结果,偶发流产组染色体数目异常率55.56％(25/45),复发性流产组(连续发生2次或2次以上的自然流产)染色体数目异常率39.06％(50/128),两者比较无统计学差异(P＞0.05).随着自然流产次数增加,胚胎染色体数目异常率呈下降趋势,但各组间无统计学差异(P＞0.05).在82例行NGS检测的病例中,染色体拷贝数变异(CNV)率在自然流产1、2、3、4次及4次以上组中分别为38.09％ (8/21)、36.67％(11/30)、31.82％ (7/22),11.1％(1/9),各组变异率均无统计学差异(P＞0.05).复发性流产组的致病性CNV率高于偶发流产组(P＞0.05).结论:染色体数目异常和拷贝数变异在自然流产患者中的发生率均高于正常人群,但与自然流产次数无关.

目的 评估无锡地区外周血胎儿染色体非整倍高通量测序(NIPT)技术在胎儿染色体非整倍体疾病筛查中的应用价值及筛查效率.方法 收集2015年4月至2017年9月于南京医科大学附属无锡妇幼保健院就诊、行NIPT并完成妊娠结局随访的单胎妊娠孕妇10269例.对NIPT结果 为高风险的孕妇,建议进行羊膜腔穿刺行产前诊断,低风险者随访妊娠结局.评价无锡地区NIPT在筛查胎儿常见染色体疾病的敏感性、特异性、阴阳性预测值等指标.结果10269例单胎妊娠孕妇中,高风险131例(1.27％,131/10269),NIPT对筛查T21、T18、T13的敏感性分别为97.29％、100％、100％,特异性分别为99.98％、99.92％、99.97％,筛查T21、T18、T13阳性预测值分别为94.74％、39.46％、57.14％,阴性预测值分别为99.99％、100％、100％.结论 NIPT对T21的产前筛查效率近似诊断水平,对染色体数目异常嵌合体也有一定的筛查价值,对性染色体、常染色体拷贝数异常的筛查效率有待进一步提高.

To explore the differential protein profile of preeclampsia and identify its potential biomarker.

Objective. Ovarian cancer is one of the most serious disease in female reproductive system. Platinum is the first-line drug for the treatment of ovarian cancer, while the resistance of platinum drug in clinical hindered the relief ovarian cancer. Our previous study found that decreased FOXO3a might be a poor prognosis in human ovarian cancer. In this research, we study whether FOXO3a was involved in the mechanism of platinum drug resistance. Methods. The CCK-8 and FACS analysis were used to monitor the survival of ovarian cancer, and the FOXO3a expression was detected by western-blot. Results. We found that FOXO3a expression upregulated significantly in A2780 compared with A2780/DDP cells with the treatment of platinum. Moreover, overexpression of FOXO3a in ovarian cancer inversed the platinum resistance in ovarian cancer. Conclusion. These observations reminded that the role of FOXO3a might be one of the critical mechanisms in developing platinum drug resistance in ovarian cancer. (C) 2018 IMSS. Published by Elsevier Inc.

This present study was designed to investigate the effects of alpha-1-antitrypsin (AAT) on oxidative stress in preeclampsia (PE) by regulating p38 mitogen-activated protein kinase (p38MAPK) signaling pathway. HTR8/SVneo cells were randomly assigned into normal, hypoxia/reoxygenation (H/R), HR + AAT and HR + siRNA-AAT groups. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to detect the mRNA and protein expressions of p-p38MAPK, AAT, signal transducer and activator of transcription 1 (STAT1) and activating transcription factor2 (ATF2). Flow cytometry, scratch test, cell counting kit-8 (CCK-8) assay and the 3-(4,5)-dimethylthiazol (-z-y1)-3,5-di- phenyltetrazolium bromide (MTT) assay were conducted to detect reactive oxygen species (ROS) and cell apoptosis, cell migration, proliferation and cytotoxicity, respectively. Mouse models in PE were established, which were divided into normal pregnancy (NP), PE and PE + AAT groups with blood pressure and urine protein measured. Chromatin immunoprecipitation (ChIP) and enzyme-linked immunosorbent assay (ELISA) were conducted to detect the activity of oxidative stress-related kinases and expressions of inflammatory cytokines and coagulation-related factors in cells and mice placenta. Immunohistochemistry, Western blotting and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were performed to detect AAT and p38MAPK expressions, apoptosis-related protein expressions, and apoptosis rate in mice placenta. Compared with the normal group, the H/R group had decreased expression of AAT, activity of superoxide dismutase (SOD) and GSH-Px, cell proliferation and migration, but increased p38MAPK, STAT1, ATF2, MDA, H2O2, inflammatory cytokines, coagulation-related factors, cell cytotoxicity, ROS, apoptotic factors and apoptosis rate. Compared with the H/R group, the HR + ATT group had increased expressions of AAT, activity of SOD and GSH-Px, cell proliferation and migration but decreased p38MAPK, STAT1, ATF2, malonyldialdehyde (MDA), H2O2, inflammatory cytokines and coagulation-related factors, cell cytotoxicity, ROS, apoptotic factors and apoptosis rate, while opposite results were observed in the HR + siRNA-ATT group. Compared with the NP group, the PE group had decreased activity of SOD and GSH-Px but increased MDA, H2O2, AAT, p38MAPK, inflammatory cytokines, coagulation-related factors and apoptosis rate. The indexes in the PE + AAT group were between the NP and PE groups. Thus, we concluded that AAT suppressed oxidative stress in PE by inhibiting p38MAPK signaling pathway.