In recent years,research on human microbiota has become more and more in-depth.It has been found that microorganisms in human body affect the functions of the host's digestive,nervous,immune and many other systems,imperceptibly changing the growth and development of human beings and disease progression.This review summarized the results of research on intestinal microbiota in early life,suggesting that the period from early pregnancy to two years old is a critical period for the colonization of human gut microbiota.It is vital to understand and investigate the factors influencing bacterial colonization at this time.

Objective:To analyze the changes of preterm birth rate and proportion of multipara in 10 years, and to explore the possibility of multipara as a risk factor for preterm birth.Methods:This study was a cohort study. The general clinical data and pregnancy outcomes of 53 979 parturients delivered in Peking University First Hospital from January 2013 to December 2022 were collected, and the changes of preterm birth rate and proportion of multipara in the past 10 years were analyzed retrospectively. Single factor and multivariate logistic regression analysis were used to explore the risk factors of spontaneous preterm birth and the influence of multipara on pregnancy outcome.Results:(1) The total preterm birth rate of 53 979 parturients was 8.3%(4 478/53 979), and the overall preterm birth rate showed an upward trend in the past 10 years, among which the preterm birth rate was higher in 2017 and 2018, which were 8.9% and 9.2% respectively. The proportion of multipara was 24.9% (13 440/53 979), which showed a trend of rising first, then declining and then stabilizing. In 2017 and 2018, the proportion of multipara was the highest, accounting for 35.0%. (2) Multivariate logistic regression analysis showed that multipara was a risk factor for spontaneous preterm birth before 37 weeks of pregnancy ( OR=1.678, 95% CI: 1.523-1.850; P<0.001), which was also a risk factor for spontaneous preterm birth before 34 weeks of pregnancy ( OR=1.937, 95% CI: 1.632-2.301; P<0.001). The high risk factors of spontaneous preterm birth also include multiple pregnancies, hyperglycemia during pregnancy, abnormal amniotic fluid volume, premature rupture of membranes, intrauterine infection, cervical incompetence, history of cervical surgery and abnormal uterine development. (3) Compared with primiparas, multiparas was older, had earlier delivery weeks, higher premature delivery rate, higher birth weight and fewer multiple pregnancies. Among pregnancy complications, the incidence of gestational diabetes mellitus, placenta previa, placenta implantation, urgent delivery and macrosomia was higher, while the incidence of pregnancy-induced hypertension, pre-eclampsia, intrahepatic cholestasis of pregnancy, oligohydramnios, fetal growth restriction, premature rupture of membranes, intrauterine infection and postpartum hemorrhage was lower, and the differences were statistically significant ( P<0.05). Conclusions:In recent 10 years, the overall rate of preterm birth is on the rise, and the risk factors of preterm birth are basically similar to those in previous studies. Multipara is a high-risk group of spontaneous preterm birth, and the risk of various pregnancy complications increases, which should be paid attention to in pregnancy care.

OBJECTIVETo research and compare HLA-DQB1 gene frequency(GF) and polymorphism distribution between south and north population of Chinese in China.

METHODSCombining PCR-sequence specific primers(SSP) and sequence specific oligonucleotide probe(SSOP) techniques and DNA Microarray Kit for HLA-DQB1 Low Res Genotyping from Shenzhen Yi-Shengtang Biological LTD. Co. was used to type HLA-DQB1 gene polymorphisms of 700 individuals living in south China and 320 individuals in north China.

RESULTSWe inspected 10 alleles of HLA-DQB1 and got a series of comprehensive and accurate statistic data.

CONCLUSIONIt is tested that HLA-DQB1*02, 05, 0601, 0602, 0603 gene frequencies are different obviously(P<0.05) between south and north Chinese. And those data will be useful to kinds of research associated with disease relevant and anthropology research.

Alleles ; Asian Continental Ancestry Group ; genetics ; China ; ethnology ; Female ; Gene Frequency ; Genetic Variation ; HLA-DQ Antigens ; genetics ; HLA-DQ beta-Chains ; Humans ; Male ; Oligonucleotide Array Sequence Analysis ; methods ; Oligonucleotide Probes ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Sequence Analysis, DNA

Objective To investigate the distribution characteristics of the gut microbiome in infants with different delivery mode and feeding pattern at six weeks of life.Methods A total of 60 infants delivered between June and September in 2017 at Peking University First Hospital were recruited.According to delivery modes and feeding patterns,they were respectively divided into two groups,which were vaginal delivery (n=42)and cesarean delivery (n=18) groups,and exclusively breastfeeding (n=40) and mixed-feeding (n=20) groups.Stool samples of all subjects were collected at six weeks after birth.The V3-V4 region of 16s rRNA gene was sequenced on Illumina Hiseq 2500 platform,and the results were analyzed with SILVA database and QIIME software.Independent samples t-test or Mann-Whitney U test was used for statistical analysis.Results (1)Eight bacterial phyla and 146 genera were identified in the 60 stool samples.Firmicutes,Proteobacteria,Actinobacteria and Bacteroidetes were four dominant phyla,and Bifidobacterium,Clostridium,Klebsiella,Bacteroides,Streptococcus,Escherichia-Shigella,Veillonella and Faecalibacterium were the top eight most abundant genera.(2) At the phyla level,the vaginal delivery group was characterized with reduced Firmicutes (0.56 ± 0.1 0 vs 0.42± 0.20,t=2.94,P＜0.05) and increased Actinobacteria and Bacteroidetes [0.04 (0.01-0.11)vs 0.20 (0.05-0.36),U=223,P＜0.05;0.05 (0.01-0.23) vs 0.09 (0.02-0.29),U=315,P＜0.05] as compared with the cesarean delivery group.However,there was no significant difference in the four dominant phyla between exclusively breastfeeding and mixed-feeding groups (all P＞0.05).At the genus level,the relative abundance of Bifidobacterium was higher in the vaginal delivery group than in the cesarean delivery group [0.19 (0.02-0.36) vs 0.01 (0.00-0.07),U=210,P＜0.01].Similarly,there was no significant difference in the eight dominant genus between exclusively breastfeeding and mixed-feeding groups(all P＞0.05).(3) The vaginal delivery group showed significantly lower Shannon and Simpson indexes than the cesarean delivery group [4.26 (3.61-5.52) vs 5.48± 1.19,U=227,P＜0.05;0.86±0.08 vs 0.94 (0.92-0.97),U=194,P＜0.05],while no significance was found in operational taxonomic unit (OTU) number and Chaol index (all P＞0.05).However,there was no significant difference in OTU number,Chaol,Shannon or Simpson index between the exclusively breastfeeding and the mixed-feeding groups (all P＞0.05).Conclusion The early infancy is a critical period for the establishment of gut microbiome.Significant differences in the composition and diversity of gut microbiota are found between infants born vaginally and abdominally,but not in infants with different feeding patterns.

Objective To investigate the gut microbial profiles of gestational mellitus diabetes (GDM) patients before and after treatment,and the relationship between gut microbiota and blood glucose level measured in 75 g oral glucose tolerance test (OGTT).Methods A prospective cohort-based nested case-control study was conducted in Peking University First Hospital from October 2016 to December 2017.Forty-five pregnancies at 24-28 gestational weeks with GDM (GDM group) and 45 healthy gravidas (control group)matched for age and pre-pregnancy body mass index (BMI) were involved.Stool samples of all participants were collected before (24-28 gestational weeks) and after (36-40 gestational weeks) treatment.The V3-V4 region of the 16S rRNA gene was sequenced on the Illumina Hiseq 2500 platform,and the results were analyzed.QIIME software was used for bioinformatics analysis.Student's t-test,Mann-Whitney U test,and Chi-square test were used for statistical analysis.Results (1) Before treatment,the Alpha diversity of the GDM group was significantly reduced compared with that of the control group (Chaol index:443.9±72.9 vs 474.0± 63.3,t=2.104,P＜0.05;Shannon index:5.6±0.5 vs 6.0±0.5,t=2.002,P＜0.05),and a significant difference in Beta diversity was also observed between the two groups (R2=0.04,P＜0.05).However,a significant difference was shown in neither Alpha nor Beta diversity between the two groups after the treatment.(2) Before treatment,the relative abundances of Blautia and Faecalibacterium of the GDM group were significantly higher than those of the control group [M (P25-P75):0.016 (0.009-0.022) vs 0.011 (0.007-0.016),U=782.000;0.114 (0.076-0.14 1) vs 0.091 (0.061-0.126),U=752.000;both P＜0.05],but the relative abundances ofAkkermansia,Odoribacter and Butyricimonas were significantly lower [0.001 (0.000-0.002) vs 0.001 (0.000-0.005),U=745.000;0.001 (0.000-0.004) vs 0.004 (0.001-0.006),U=766.500;0.001 (0.000-0.003) vs 0.003 (0.001-0.005),U=710.000;all P＜0.05].(3) A negative relationship was found between the fasting glucose level of OGTT and the relative abundances of Akkermansia,Odoribacter and Butyricimonas (r=-0.325,-0.273 and-0.284;all P＜0.05),and between the one-hour-OGTT glucose level and the relative abundances of Akkermansia and Butyricimonas (r=-0.285 and -0.265,both P＜0.05).The two-hour-OGTT glucose level was positively related to the relative abundance of Faecalibacterium (r=0.278,P＜0.05),but negatively related to the relative abundance ofAkkermansia (r=-0.245,P＜0.05).The area under the OGTT time-glucose curve was negatively related to the relative abundances of Akkermansia and Butyricimonas (r=-0.321 and-0.264,both P＜0.05).Conclusions There are significant differences in gut microbial composition and structure between GDM and healthy pregnant women,which are significantly associated with OGTT blood glucose level.Euglycemia achieved after GDM management could improve gut microbiota disorder.

The present study aimed to investigate the inhibitory effect and mechanism of Isodon terricolous-medicated serum on lipopolysaccharide(LPS)-induced hepatic stellate cell(HSC) activation. LPS-induced HSCs were divided into a blank control group, an LPS model group, a colchicine-medicated serum group, an LPS + blank serum group, an I. terricolous-medicated serum group, a Toll-like receptor 4(TLR4) blocker group, and a TLR4 blocker + I. terricolous-medicated serum group. HSC proliferation was detected by methyl thiazolyl tetrazolium(MTT) assay. Enzyme-linked immunosorbent assay(ELISA) was used to measure type Ⅰ collagen(COL Ⅰ), COL Ⅲ, transforming growth factor-β1(TGF-β1), intercellular adhesion molecule-1(ICAM-1), α-smooth muscle actin(α-SMA), vascular cell adhesion molecule-1(VCAM-1), cysteinyl aspartate-specific proteinase-1(caspase-1), and monocyte chemotactic protein-1(MCP-1). Real-time PCR(RT-PCR) was used to detect mRNA expression of TLR4, IκBα, and NOD-like receptor thermal protein domain associated protein 3(NLRP3), nuclear factor-κB(NF-κB) p65, gasdermin D(GSDMD), and apoptosis-associated speck-like protein containing a CARD(ASC) in HSCs. Western blot(WB) was used to detect the protein levels of TLR4, p-IκBα, NF-κB p65, NLRP3, ASC, and GSDMD in HSCs. The results showed that I. terricolous-medicated serum could inhibit the proliferation activity of HSCs and inhibit the secretion of COL Ⅰ, COL Ⅲ, α-SMA, TGF-β1, caspase-1, MCP-1, VCAM-1, and ICAM-1 in HSCs. Compared with the LPS model group, the I. terricolous-medicated serum group, the colchicine-medicated serum group, and the TLR4 blocker group showed down-regulated expression of p-IκBα, NLRP3, NF-κB p65, GSDMD, and ASC, and up-regulated expression of IκBα. Compared with the TLR4 blocker group, the TLR4 blocker + I. terricolous-medicated serum group showed decreased expression of TLR4, p-IκBα, NLRP3, NF-κB p65, GSDMD, and ASC, and increased expression of IκBα. In conclusion, I. terricolous-medicated serum down-regulates HSC activation by inhibiting the TLR4/NF-κB/NLRP3 signaling pathway.
NF-kappa B/metabolism* ; Hepatic Stellate Cells ; Transforming Growth Factor beta1/metabolism* ; NF-KappaB Inhibitor alpha/metabolism* ; Intercellular Adhesion Molecule-1/metabolism* ; Isodon ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Toll-Like Receptor 4/metabolism* ; Vascular Cell Adhesion Molecule-1/metabolism* ; Lipopolysaccharides/pharmacology* ; Signal Transduction ; Colchicine/pharmacology* ; Caspases