Objective To determine the relationship between local microenvironment and cervical cancer (CC). Discovering differential florae and metabolites associating with CC. Design Observational study. Participants 10 LSIL patients, 10 HSIL patients, 10 CC patients and 10 healthy controls were enrolled in our study. Methods We performed 16S rDNA sequencing and metabolomic analysis in the cervicovaginal fluid to reveal the differential florae and metabolites during cervical carcinogenesis. Results Carcinogenesis was associated with alterations in microbiome diversity, individual taxa, and functions. Bacterial diversity was increased and the composition was changed by the influence of cervical cancer carcinogensis. Lactobacillus was significantly reduced in LSIL and CC patients. On the contrary, the relative abundance of Prevotella was significantly elevated in LSIL patients. Lipids were significantly declined in LSIL and HSIL patients compared to HC participants, and significantly elevated in CC compared to LSIL and HSIL patients. Pathway enrichment analysis found phenylalanine, tyrosine and tryptophan biosynthesis pathway was crucial in cervical carcinogenesis. Conclusions These results showed that microbic and metabolomic profiling are capable of distinguishing CC from precancer and highlighted potential biomarkers for the early detection of cervical dysplasia. These differential microorganisms and metabolites expected to become a potential tool to assist in the diagnosis of cervical cancer. Funding We would like to thank Development & Demonstration Program of Wuxi (N20192004), Key Research & Development Program of Jiangsu Province (BE2015617), The 5th Phase of “Project 333” of Jiangsu (BRA2019024) and Innovation and Entrepreneurship Training Program for College Students in Jiangsu Province (KYCX19_1182) for their support.

Premature rupture of membranes (PROM), with a prevalence of 15.3

BACKGROUND:Premature rupture of the membranes (PROM) is a key cause of preterm birth and represents a major cause of neonatal mortality and morbidity. Natural products N-acetyl-d-galactosamine (GalNAc), which are basic building blocks of important polysaccharides in biological cells or tissues, such as chitin, glycoproteins, and glycolipids, may improve possible effects of wound healing. METHODS:An in vitro inflammation and oxidative stress model was constructed using tumor necrosis-α (TNF-α) and lipopolysaccharide (LPS) action on WISH cells. Human amniotic epithelial cells (hAECs) were primarily cultured by digestion to construct a wound model. The effects of GalNAc on anti-inflammatory and anti-oxidative stress, migration and proliferation, epithelial-mesenchymal transition (EMT), glycosaminoglycan (GAG)/hyaluronic acid (HA) production, and protein kinase B (Akt) pathway in hAECs and WISH cells were analyzed using the DCFH-DA fluorescent probe, ELISA, CCK-8, scratch, transwell migration, and western blot to determine the mechanism by which GalNAc promotes amniotic wound healing. RESULTS:GalNAc decreased IL-6 expression in TNF-α-stimulated WISH cells and ROS expression in LPS-stimulated WISH cells (P < 0.05). GalNAc promoted the expression of Gal-1 and Gal-3 with anti-inflammatory and anti-oxidative stress effects. GalNAc promoted the migration of hAECs (50% vs. 80%) and WISH cells through the Akt signaling pathway, EMT reached the point of promoting fetal membrane healing, and GalNAc did not affect the activity of hAECs and WISH cells (P > 0.05). GalNAc upregulated the expression of sGAG in WISH cells (P < 0.05) but did not affect HA levels (P > 0.05). CONCLUSIONS:GalNAc might be a potential target for the prevention and treatment of PROM through the galectin pathway, including (i) inflammation; (ii) epithelial-mesenchymal transition; (iii) proliferation and migration; and (iv) regression, remodeling, and healing.

Cervical cancer (CC) continues to be one of the most common cancers among females worldwide. It takes a few years or even decades for CC to arise in a minority of women with cervical precancers. An increasing corpus of studies today indicates that local microecology and carcinogenesis are intimately related. To investigate the changes in cericovaginal microecology with the development of cervical cancer, we performed 16S rDNA sequencing and metabolomic analysis in cericovaginal fluid from 10 LSIL patients, 10 HSIL patients, 10 CC patients and 10 healthy controls to reveal the differential flora and metabolites during cervical carcinogenesis. Carcinogenesis is associated with alterations in microbiome diversity, individual taxa, and functions with notable changes in Lactobacillus, Prevotella and Aquabacterium, as well as in cervicovaginal metabolites that correlate with cervicovaginal microbial patterns. Increased bacterial diversity and a decline in the relative abundance of Lactobacillus, the dominant species in the cericovaginal flora, are observed when cervical lesions advance. According to KEGG pathway enrichment analysis, lipids and organic acids change as cervical cancer progresses, and the phenylalanine, tyrosine, and tryptophan biosynthesis pathway is essential for the development of cervical cancer. Our results reveal that microbic and metabolomic profiling is capable of distinguishing CC from precancer and highlights potential biomarkers for the early detection of cervical dysplasia. These differential microorganisms and metabolites are expected to become a potential tool to assist in the diagnosis of cervical cancer.

In China, premature rupture of membranes (PROM) counts as a major pregnancy complication in China and usually results into adverse pregnancy outcomes. We analysed the vagina microbiome composition using 16S rDNA V3–V4 amplicon sequencing technology, in this prospective study of 441 women in their third trimester of pregnancy. We first divided all subjects into PROM and HC (healthy control) groups, in order to investigate the correlation of vagina microbiome composition and the development of PROM. We found that seven pathogens were higher in the PROM group as compared to the HC group with statistical significance. We also split all subjects into three groups based on Lactobacillus abundance-dominant (Lactobacillus > 90%), intermediate (Lactobacillus 30–90%) and depleted (Lactobacillus < 30%) groups, and explored nine pathogenic genera that were higher in the depleted group than the intermediate and dominant groups having statistical significance. Finally, using integrated analysis and logistics regression modelling, we discovered that Lactobacillus (coeff = −0.09, p = 0.04) was linked to the decreased risk of PROM, while Gardnerella (coeff = 0.04, p = 0.02), Prevotella (coeff = 0.11, p = 0.02), Megasphaera (coeff = 0.04, p = 0.01), Ureaplasma (coeff = 0.004, p = 0.01) and Dialister (coeff = 0.001, p = 0.04) were associated with the increased risk of PROM. Further study on how these pathogens interact with vaginal microbiota and the host would result in a better understanding of PROM development.

Cervical cancer(CC)continues to be the second leading cause of cancer death in women aged 20 to 39[1].Recent research has shown that the cervical microbiota differs in different stages of cervical carcinogenesis[2].It has been reported that the gut microbiota is linked to host metabolism,which influences the progression of the disease[3].The role of cervicovaginal flora in affecting host metabolism,thereby causing the progression of cervical cancer,requires further research.In this direction,metabolomics has been implemented to detect small molecular differential metabolites in cancer progression.Metabolomics is the study of the thousands of low-molecular-weight molecules found in biological fluids and tissues of different individuals,whether normal or afflicted with disease,and it reflects reasonable changes in biological functions.

BACKGROUND:Premature rupture of membranes (PROM) is a major pregnancy complication in China and usually leads to adverse pregnancy outcomes. The major aim of this study was to search for microorganisms and their related metabolites that have direct relationship with PROM.METHODS:For vaginal discharge samples, metagenomics sequencing was applied to identify microorganisms that were enriched in PROM subjects, and untargeted metabolomics was applied to characterize the metabolites changes in PROM subjects compared to healthy controls (HC). Correlation analysis was then used to explore the relationship between these microorganisms and metabolites changes.RESULTS:Two upstream metabolites of glycolysis, N-acetyl-D-galactosamine (GalNAc) and sucrose, were found downregulated in the PROM group (P=0.04 and P=0.041, respectively). Higher percentages of conditional pathogens, such as of Streptococcus (8.4% vs. 6.1% in HC group, P=0.15) and Chlamydia (4.3% vs. 2.3% in HC group, P=0.07) were found in PROM group. Other common conditional pathogens including Prevotella, Staphylococcus, Mycobacterium and Enterobacter, were also higher in PROM group, although their absolute percentages were low and the differences did not reach statistical significance due to relative small sample size. Correlation analysis further demonstrated a positive correlation of downregulation of glycolysis metabolites with higher percentage of conditional pathogens.CONCLUSIONS:Integrated metagenomics and metabolomics analysis can be used to track the subtle changes in the vaginal microenvironment. Downregulation of glycolysis substrates (GalNAc and sucrose) and increase of related pathogenic microorganisms (Streptococcus and Chlamydia) could serve as early warning biomarkers of PROM.

目的 多中心回顾性地分析无锡地区阴道感染的城乡差异.方法 筛选2017年6月1日至2018年6月30日就诊于江苏省无锡市各级医院(包括城区、滨湖区、惠山区、锡山区、新吴区、宜兴市、江阴市)的阴道炎患者数据,使用EpiData3.1软件建立数据库并进行数据录入,采用SPSS20.0软件进行统计分析.结果 乡村35岁以上的阴道炎患者占乡村总患者人数的64.4％,而城市仅占52.2％;乡村阴道炎患者清洁度异常率和单一感染率分别为42.1％和90.2％,而城市分别为28.2％和94.0％;乡村阴道炎患者中孕妇比例为4.0％,城市为28.5％.结论 相对于城市女性,乡村阴道炎患者就诊时病情更为严重和复杂;年轻女性尤其是城市的年轻女性更倾向于大医院就诊.完善分级诊疗制度、合理分配医疗资源、加强卫生教育宣教有利于女性阴道炎的早发现、早治疗.

Toll样受体(Toll Like Receptor,TLR)是一种模式识别受体( pattern recognition receptor , PRR) ,微生物及其代谢产物入侵人体是通过识别PRR,激活固有免疫从而激活抗原特异性获得性免疫系统[1-2].TLRs是一个膜受体家族,在感知包括细菌、真菌和病毒在内的多种入侵病原体方面发挥着关键作用[3-4].TLR4是人类发现的第一个TLR,是介导信号转导的重要PRR,而且是唯一可以经髓样分化因子88 ( myeloid differ-entiation primary response protein 88 , MyD88 )依赖型和β干扰素TIR结构域衔接蛋白( TIR domain-containing adaptor indu-cing interferon-β,TRIF)依赖型两条信号通路的TLR家族成员.TLR4具有多种不同结构的配体,如植物二萜紫杉醇、呼吸道合胞病毒的融合蛋白、纤连蛋白和热休克蛋白,其中最重要的配体是脂多糖[1].脂多糖是革兰阴性菌外膜的重要成分,有强大的免疫刺激活性,TLR4通过识别脂多糖激活下游信号通路,在机体的细菌感染和免疫反应中起着重要作用.

Premature rupture of membranes (PROM) is usually associated with pregnant and neonatal complications. Most of the PROM cases are caused by ascending asymptomatic genital infection. In China, PROM (15.3%) is more common than spontaneous preterm labor (7.3%) and leads to more adverse pregnancy outcomes. Here, we designed a prospective cohort study to measure the metabolomics changes in vaginal swab samples and explored their potential contribution to PROM. A total of 260 differentially expressed metabolites were identified and further analyzed. In the PROM group, N-acetyl- d -galactosamine and sucrose were downregulated ( P = 0.0025, P = 0.0195, respectively), both of which are the upstream metabolites of the glycolysis pathway. Furthermore, estriol 3-sulfate 16-glucuronide ( P = 0.0154) and 2-methoxy-17beta-estradiol 3-glucosiduronic acid ( P = 0.004), two final metabolites in steroid hormone biosynthesis, were both downregulated in the PROM group. Finally, we found two catechin metabolites (epigallocatechin-7-glucuronide, P = 0.0009; 4′-methyl-epigallocatechin-7-glucuronide, P = 0.01) as well as DL-citrulline ( P = 0.0393) were also significantly downregulated in the PROM group compared with the healthy control (HC) group, which are related to important antioxidant and anti-inflammatory activities in the human body. Altogether, metabolite changes in glycolysis, steroid hormone biosynthesis, and antioxidant/anti-inflammatory pathways may contribute to (or be a consequence of) vaginal dysbiosis and PROM. Metabolite pathway analysis is a new and promising approach to further investigate the mechanism of PROM and help prevent its unfavorable pregnant outcomes at a functional level. Trial registration number: ChiCTR2000034721

阴道微生态是由阴道的局部解剖结构、周期性的内分泌变化、阴道局部免疫系统和阴道内微生物菌群共同组成的阴道环境和生态系统.多项研究证实阴道微生态失调通过局部炎症因子释放、黏膜免疫应答的改变和局部代谢变化,可引起早产的发生.阴道内小分子物质如糖类、短链脂肪酸和胺类通过代谢路径和代谢产物在阴道微生态失调与早产的发病机制起作用.近年来,阴道微生态的理念得到重视,治疗方法由传统的抗生素治疗转向了综合治疗,目的是恢复正常阴道菌群和阴道上皮黏膜免疫系统.但阴道微生态与宿主之间存在复杂的相互作用,因此仍需要进一步的研究.

目的 探讨妊娠期糖尿病(GDM)孕妇产后糖代谢变化.方法 分别于产后42 d和2年随访165例GDM孕妇(GDM组)和169例正常孕妇(对照组)的糖代谢相关指标.结果 GDM组产后42 d和2年的空腹血糖、口服糖耐量试验2h血糖、空腹胰岛素、胰岛素抵抗指数及糖代谢异常率高于对照组(P＜0.05或P＜0.01),产后2年GDM组的腰臀比和舒张压高于对照组(P＜0.01).多因素分析提示,孕期使用胰岛素是导致GDM产后糖代谢异常的危险因素,而母乳喂养则是其保护因素.结论 GDM孕妇产后发生糖代谢异常的风险高于正常孕妇,应大力提倡母乳喂养并加强产后随访.

Macrosomia is one of the most common perinatal complications of pregnancy and has life-long health implications for the infant. microRNAs (miRNAs) have been identified to regulate placental development, yet the role of miRNAs in macrosomia remains poorly understood. Here we investigated the role of miR-17-92 cluster in macrosomia. The expression levels of five miRNAs in miR-17-92 cluster were significantly elevated in placentas of macrosomia, which may due to the up-regulation of miRNA-processing enzyme Drosha and Dicer . Cell cycle pathway was identified to be the most relevant pathways regulated by miR-17-92 cluster miRNAs. Importantly, miR-17-92 cluster increased proliferation, attenuated cell apoptosis and accelerated cells entering S phase by targeting SMAD4 and RB1 in HTR8/SVneo cells. Furthermore, we found that expression of miR-17-92 cluster in serum had a high diagnostic sensitivity and specificity for macrosomia (AUC: 80.53%; sensitivity: 82.61%; specificity: 69.57%). Our results suggested that miR-17-92 cluster contribute to macrosomia development by targeting regulators of cell cycle pathway. Our findings not only provide a novel insight into the molecular mechanisms of macrosomia, but also the clinical value of miR-17-92 cluster as a predictive biomarker for macrosomia.

目的:对孕妇进行个体化营养指导,分析其营养状况及妊娠期并发症的发生情况.方法:根据《中国居民膳食指南(2007)》,应用围产营养管理系统软件制定营养指导方案并进行孕期个体化营养指导,统计各项营养相关指标及妊娠期并发症的发生率.结果:①营养指导组孕期增重低于对照组,差异有统计学意义(P＜0.05);②营养指导组蛋白质、膳食纤维、钙、铁、维生素B1及维生素B2摄入量高于对照组,碳水化合物摄入量低于对照组,差异有统计学意义(P＜0.05);③营养指导组高密度脂蛋白(HDL)、载脂蛋白A(ApoA)高于对照组,差异有统计学意义(P＜0.05);甘油三酯(TG)低于对照组,差异有统计学意义(P＜0.05);血清铁高于对照组,差异有统计学意义(P＜0.05);④营养指导组妊娠期糖尿病、妊娠期高血压疾病及缺铁性贫血的发生率均低于对照组,差异有统计学意义(P＜0.05).结论:通过个体化营养指导,可使孕期营养更合理,有助于降低妊娠期并发症的发生率.

目的:对孕妇进行个体化营养指导控制新生儿出生体重,并分析对围产儿结局的影响.方法:根据《中国居民膳食指南2007》,使用围产营养管理系统软件制定营养指导方案进行孕期个体化营养指导,分析孕前体重指数(BMI)、孕晚期BMI、孕期增重、新生儿体重、剖宫产率、产钳助产率、产后出血率.结果:①营养指导组晚孕期BMI、孕期增重低于对照组(P＜0.05).②营养指导组的新生儿出生体重低于对照组(P＜0.05);营养指导组中新生儿出生体重2 500～3 500 g组比例高于对照组(P＜0.01).③营养指导组的剖宫产率、产钳助产率均低于对照组(P＜0.05).④新生儿出生体重2 500～3 500 g组剖宫产率、产钳助产率、产后出血率低于3 500～4 000 g组及≥4 000 g组(P＜0.01).结论:通过孕期个体化营养指导,将孕妇体重指数、孕期体重增加及新生儿出生体重控制在合理范围内,有助于降低剖宫产率,改善新生儿分娩结局.

Objective:Baduan jin for body guidance has regulating main and collateral channels,running blood,strengthening ridge to keep in good health,illnesses and fitness. The study of 54 ECG reports analysis on 22 cases keerkezi people farmers and herdsmen,ca-dres participation in standing type baduan jin more than a year considered that standing type baduan jin can not effectively improve the cardiac arrhythmia,but it will not increase the burden on the heart.

目的:比较正常孕妇、妊娠期糖尿病(GDM)孕妇、GDM并发子痫前期孕妇胎盘组织中内脂素mRNA及蛋白表达的差异.方法:采用RT-PCR法检测正常孕妇(A组)、GDM孕妇(B组)、GDM并发子痫前期孕妇(C组)胎盘组织中内脂素mRNA水平.采用Western Blot法检测3组胎盘组织中内脂素蛋白表达水平.测定并比较3组孕妇的体重指数(BMI)、空腹胰岛素及空腹血糖水平.结果:空腹胰岛素水平及胰岛素抵抗指数(HOMA-IR)从A组至C组递增,3组间两两比较差异均有统计学意义(P＜0.05).B组和C组胎盘组织中内脂素mRNA及蛋白表达水平均高于A组,差异均有统计学意义(P＜0.05).3组胎盘组织中内脂素mRNA及蛋白表达水平与空腹胰岛素、空腹血糖及HOMA-IR均无相关性(P＞0.05).结论:GDM并发子痫前期孕妇胎盘组织中的内脂素mRNA及蛋白表达水平均显著升高.

目的 探讨血清内脂素与妊娠期糖尿病(GDM)并发子痫前期的关系.方法 ELISA法检测GDM并发子痫前期孕妇(A组,12例)、GDM无子痫前期孕妇(B组,30例)和正常孕妇(C组,50例)外周血清内脂素浓度;并测定三组孕妇的平均动脉压(MAP)、空腹胰岛素(FIns)、空腹血糖(FBG)、甘油三酯(TG)、总胆固醇(TC),计算胰岛素抵抗指数(HOMA-IR)和体重指数(BMI),分析血清内脂素水平与GDM并发子痫前期的关系.结果 A组血清内脂素、FIns和HOMA-IR均高于B组(P＜0.05),B组高于C组(P＜0.01).多元回归分析显示,血清FIns水平是影响血清内脂素的重要因素.结论 GDM并发子痫前期孕妇血清内脂素水平明显升高,且与胰岛素抵抗有关.

Objective To study the Inhibitory effects of 20(S)-ginsenoside Rg3loaded human albumin nanopaticles(SPG-Rg3-HAS-NP)on human cervical cancer Hela cells in vitro.Methods Hela cells were treated with normal saline、blank human albumin nanopaticles、pure 20(S)-ginsenoside Rg3(SPG-Rg3)and 20(S)-ginsenoside Rg3loaded human albumin nanopaticles(SPG-Rg3-HAS-NP)respectively.Hela cells growth inhibition rates were detected after 24h、 48h、72hand 96hbeing treated with different drug concentration by MTT assay.Results Blank human albumin nanopaticles had no cytotoxicity on Hela cells without concentration-dependence and time-dependence in vitro.SPG-Rg3 group SPG-Rg3-HAS-NP group had significant anti-proliferation effect on Hela cells growth by MTT assay,and Hela cells growth had respectively concentration-dependence and time-dependence to SPG-Rg3group SPG-Rg3-HAS-NP group.Hela cells growth seemed to be platform phase and even have a down curve tendency after concentration of 80 μg/ml SPG-Rg3in SPG-Rg3group,but Hela cells growth had a continue ascend curve in SPG-Rg3-HAS-NP group.The SPG-Rg3-HAS-NP group had higher inhibitory effect than SPG-Rg3group after concentration of 20μg/ml SPGRg3and after 72hadministration(P0.05).The above results indicated anti-proliferation effect on Hela cells growth in SPG-Rg3-HAS-NP group had a certain time last and the SPG-Rg3-HAS-NP had a certain sustained-releasing effect.Conclusion SPG-Rg3-HAS-NP has a significant anti-proliferation effect on human cervical cancer Hela cells with concentration-dependence and time-dependence in vitro.