Pregnancy ; Female ; Humans ; Placenta Accreta/surgery* ; Cesarean Section ; Retrospective Studies ; Biomarkers ; Hysterectomy ; Placenta Previa ; Placenta

Objective:To investigate the effects of scarred uterus on endometrium receptivity and invasion of placental trophoblasts using a mouse model.Methods:A scarred uterus mouse model was established on 30 female Specific Pathogen Free mice. Full-layer incision on unilateral uteruses was performed simulating a cesarean section to establish the scarred uterus mice model and the contralateral uteruses were used as control. The number of implanted blastocysts between the scarred and non-scarred uteruses was compared at 4.5 d after conception (windows of implantation, WOI). The morphology of pinopod was observed under electron microscopy, and the expression of endometrial receptivity-related molecules, such as leukemia inhibitor factor (Lif) and mucin-1 (MUC1), and mRNA of Lif and MUC1 were analyzed by immunohistochemistry and reversed transcription-polymerase chain reaction technique, respectively. During the placental formation period (day 13.5, 15.5, and 17.5 after conception), the development of the decidual layer, junction layer, and labyrinth layer of the placenta were observed under microscope, and the distribution of glycogenotrophoblast cells and the location of CK7-traced invasion trophoblasts were determined with immunohistochemistry. Paired t test and one-way analysis of variance were used for statistical analysis. Results:Compared with the control side, the number of blastocysts implantation on the scarred uterus decreased significantly at 4.5 d after conception (3.50±0.54 vs. 1.33±0.81, t=7.05, P=0.001). In the WOI, the scarred uteruses were found to have decreased scores of endometrial pinopodes coverage (1.60±0.44 vs. 2.75±0.28, t=15.06, P<0.001), decreased mRNA expression of Lif (0.71±0.12 vs. 1.49±0.30, t=5.16, P=0.004) and increased MUC1 mRNA [(2.19±0.45) vs.(1.03±0.17), t=7.51, P<0.001] comparing with the control. No significant changes in the area and general morphology were observed in the three different layers on either side during the placental formation period. In terms of trophoblast invasion, the grayscales of glycogen trophoblast cells in the junction layer and near the decidua layer on the scarred side were higher than those of the control on day 15.5 (31.01±1.502 vs. 23.63±0.90, t=12.76, P<0.001) and day 17.5 (31.96±2.37 vs. 24.03±1.87, t=4.36, P=0.008), respectively. In the mature placenta on the scarred side on day 18.5, CK7+ traced trophoblast cells were abundant in the decidua layer near the maternal side, showing an overall excessive trophoblast invasion. Conclusion:Scarred uterus in mice affects the endometrial function, contributing to reduced endometrial receptivity during pregnancy and excessive invasion of trophoblasts during placental development after implantation.

The information arising from pedigree analysis is important for clinicians to understand the inheritance pattern of the disease, filter the testing data, and provide suggestions to other family members. Along with the development and clinical implementation of new genetic testing, an increasing number of "positive" results are obtained and pedigree analysis is required to further verify the pathogenicity.

Objective:To evaluate the efficacy and safety of modified Atkins diet (MAD) in treating global growth retardation (GDD).Methods:A prospective multicenter clinical controlled study was conducted.The children were included from 8 departments of children′s rehabilitation in Henan Province from July 2017 to October 2017.A total of 154 children who met the inclusion criteria were randomly assigned into the routine treatment group (88 cases) and MAD therapy group (66 cases). A total of 62 children in MAD therapy group and 59 children in routine treatment group completed the study for 15 months.The routine treatment group was provided comprehensive rehabilitation training, and the MAD therapy group was given MAD treatment on the basis of rehabilitation training.Two-way repeated-measures ANOVA was used to compare the differences among datas at different time points. Results:After 3 months, there were significant differences in the scores of the Chinese Version of Urban Infant-Toddler Social and Emotional Assessment (CITSEA)/Achenbach Children′s Behavior Scale (CBCL) between the 2 groups (all P<0.05). Significant improvement was seen in the MAD group.After 6 months, the MAD therapy group had significantly higher scores on the Gesell Developmental Scale for language and social behavior than the routine treatment group (all P<0.05). After 9 months, the scores of the children in the MAD therapy group were better than those in the routine treatment group in the Gesell Developmental Scale adaptive energy area and the infant-junior high school student social life scale (S-M scale), and the differences were statistically significant (all P<0.05). After 15 months, the fine motor in the MAD therapy group was better than that in the routine treatment group ( P<0.05). At the early stage of MAD therapy, 28 patients showed mild adverse reactions that were reversed after symptomatic treatment.No severe adverse reactions were observed. Conclusions:MAD therapy can improve the neuro-development, emotional and social behaviors, and adaptive behaviors with no severe adverse effects.

Objective:To explore the effect of exercise intervention on regulation of Toll-like receptor 4 (TLR4) signaling pathway in overweight and obese pregnant women.Methods:The cohort was based on a randomized controlled trial (RCT) carried out by the same research group in Peking University First Hospital from December 2014 to July 2016. Overweight and obese patients who delivered by elective cesarean section without pregnancy complications were recruited, among which 12 cases in the exercise group and 11 cases in the control group were selected. Real-time polymerase chain reaction, Western Blot, and Luminex experiments were used to compare the expression of TLR4-myeloid differentiation factor 8(MyD88)-nuclear factor-κB(NF-κB) pathway in peripheral blood mononuclear cell (PBMC), rectus abdominis muscle, omental adipose, and subcutaneous adipose, as well as the levels of inflammatory factors (TNF-α, IL-1β, IL-10) in plasma between the two groups. Two independent samples t-test, generalized estimating equation, Chi-square test, and Pearson correlation analysis were adopted for statistical analysis. Results:(1) The expression of inflammatory factors TNF-α and IL-1β in the exercise group showed a downward trend compared with the control in the second and third trimester, but none of the differences were statistically significant (all P>0.05). (2) The mRNA expression of TLR4, MyD88, and NF-κB and the protein expression of TLR4 and NF-κB in PBMC of the exercise group were significantly lower than those in the control group during pregnancy (TLR4 mRNA: 0.06±0.03 vs 0.10±0.04 in the second trimester, 0.05±0.02 vs 0.11±0.05 in the third trimester, χ2=8.07; MyD88 mRNA: 0.09±0.03 vs 0.11±0.03 in the second trimester, 0.10±0.04 vs 0.17±0.06 in the third trimester, χ2=5.81; NF-κB mRNA: 0.10±0.03 vs 0.17±0.08 in the second trimester, 0.08±0.03 vs 0.20±0.08 in the third trimester, χ2=14.71; TLR4 protein: 1.7±0.5 vs 1.9±0.8 in the second trimester, 1.7±0.4 vs 2.3±0.8 in the third trimester, χ2=5.83; NF-κB protein: 1.0±0.4 vs 1.5±0.4 in the second trimester, 1.2±0.3 vs 1.5±0.5 in the third trimester, χ2=4.73; all P<0.05). Moreover, the differences in the mRNA expression of TLR4, MyD88, and NF-κB and TLR4 protein expression in PBMC between the two groups gradually increased. (3) NF-κB in rectus abdominis and omental adipose tissue (0.04±0.02 vs 0.08±0.04, t=－3.72; 0.25±0.05 vs 0.63±0.21, t=－5.41; both P<0.05) and TLR4 and MyD88 in subcutaneous adipose tissue (0.12±0.03 vs 0.30±0.10, t=－5.30; 0.24±0.09 vs 0.44±0.08, t=－5.38; both P<0.05) were observed a decreased mRNA level in the exercise group compared with the control group. The protein level of MyD88 and NF-κB in omental adipose tissue and NF-κB in subcutaneous adipose tissue in the exercise group were significantly lower than those in the control group (1.1±0.5 vs 2.0±0.8, t=－3.15; 1.3±0.5 vs 2.0±0.9, t=－2.23; 1.2±0.5 vs 1.9±0.8, t=－2.80, all P<0.05). (4) The expressions of TLR4 and NF-κB mRNA ( r=0.453 and 0.485) in rectus abdominis muscle, NF-κB mRNA, TLR4 and MyD88 protein ( r=0.539, 0.437 and 0.527) in omental adipose in the two groups were positively correlated with the level of fasting blood glucose ( P<0.05). Conclusions:Regular exercise during pregnancy can down-regulate the expression and activation of the TLR4-MyD88-NFκB pathway in overweight and obese pregnant women. The expression of related factors along this pathway has a certain correlation with fasting blood glucose.

Along with the development of screening, diagnostic and therapeutic technologies, the spectrum of fetal abnormalities has been constantly expanded. This brings increasing challenges to the clinical diagnosis and treatment, including but not limited to optimizing multidisciplinary cooperation, options of prenatal genetic testing methods, the uncertainty in the transition period of new technology implementation, and the comprehensiveness of genetic counseling before and after testing. We discuss the above issues aiming to meet the dilemma and achieve the leap of fetal medicine to the advanced level through multidisciplinary collaboration resulting in the improvement of diagnosis and treatment efficiency.

Objective:To observe the effect of observing good swallowing on the swallowing action of stroke survivors with dysphagia.Methods:Eighteen stroke survivors with dysphagia were randomly divided into a treatment group ( n=9) and a control group ( n=9). In addition to routine swallowing rehabilitation therapy, the treatment group was asked to simulate swallowing after watching a video of normal people′s swallowing action. They did so 5 times a week for 10 minutes, while the control group just watched landscape videos at the same time. The treatment lasted 8 weeks. Before and after the treatment, both groups were assessed using the eating assessment tool (EAT-10), the functional oral intake scale (FOIS) and the penetration and aspiration scale (PAS). Functional magnetic resonance imaging (fMRI) was also used to observe their swallowing action. Results:There was no significant difference between the two groups in any of the measurements before the treatment. After the 8 weeks of treatment the average EAT-10, FOIS and PAS scores of the treatment group were all significantly better than before the treatment and better than the control group′s averages at the time. fMRI showed significantly more areas activated in the precuneus, parietal lobe, posterior central gyrus, BA7, BA5, frontal lobe and paracentral lobule in the treatment group compared with before the intervention and also more than in the control group.Conclusions:Observing proper swallowing action can improve dysphagia and activation of the swallowing-related brain areas of stroke survivors.

Adult ; Body Temperature/drug effects* ; COVID-19/pathology* ; Drug Therapy, Combination ; Drugs, Chinese Herbal/therapeutic use* ; Ephedra sinica/chemistry* ; Female ; Fever/pathology* ; Glycyrrhiza/chemistry* ; Humans ; Indoles/administration & dosage* ; Male ; Medicine, Chinese Traditional/methods* ; Middle Aged ; Phytotherapy/methods* ; Pneumonia, Viral/pathology* ; Radiography, Thoracic ; SARS-CoV-2/drug effects*

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.

Objective:To investigate the optimal cut-off of sequential screening for Down syndrome (DS) with a cost-effectiveness analysis.Methods:A theoretical model, covering 1 000 000 singleton pregnancies, was established with the parameters from published articles and on-the-spot investigation. Two screening strategies were involved and both required conventional second-trimester serum triple screening first. For the next step, strategyⅠ was followed by cell-free fetal DNA (cffDNA) testing if the cut-offs were higher than 1/300 (Ⅰ-1) or 1/1 000 (Ⅰ-2), and if cffDNA testing indicated high risk, prenatal diagnostic testing would be performed. While strategy Ⅱ was followed by prenatal diagnostic testing in high-risk populations with cut-offs higher than 1/10 (Ⅱ-1), 1/50 (Ⅱ-2), 1/100 (Ⅱ-3), 1/150 (Ⅱ-4), 1/200 (Ⅱ-5), 1/250 (Ⅱ-6) or 1/300 (Ⅱ-7), or cffDNA testing for those with intermediate risks. The primary outcome was an incremental cost analysis on the baseline and alternative assumptions. The strategy was defined as "appropriate" when the incremental cost was less than the cost of raising one DS child. The secondary outcomes included total cost, cost-effectiveness analysis, cost-benefit analysis, and screening efficiency.Results:(1) More DS cases and less survived miss-diagnosed cases were detected by strategy Ⅱthan strategyⅠ (Ⅰ-1: 1 921, Ⅰ-2: 2 199 vs Ⅱ-1 to Ⅱ-7: 2 202-2 212; Ⅰ-1: 312; Ⅰ-2: 100 vs Ⅱ-1 to Ⅱ-7: 98-90). The total prenatal diagnosis cases and the number of case requring prenatal diagnosis for detecting one DS case were the lowest in strategy Ⅰ-1 group (2 081; 1.1, 2 081/1 921) and were the highest in Strategy Ⅱ-7 group (82 385; 37.2, 82 385/2 212). (2) Strategy Ⅰ-1 was the most cost-effective approach with the lowest total cost (￥928.896 million) and cost-effectiveness (￥237 000), and the highest benefit/cost ratio (4.90), followed by strategy Ⅱ-7 (￥957.380 million, ￥371 000 and 3.11). The most costly strategy was Ⅰ-2 (￥1 040.883 million, ￥404 000 and 2.85). (3) Setting strategyⅠ-1 as the baseline, strategyⅠ-2 had the highest incremental cost (￥1.580 million). The incremental cost of strategy Ⅱ ranged from ￥1.535 million (Ⅱ-1) to ￥1.259 million (Ⅱ-7), close to or less than the cost of raising a DS child (￥1.52 million). (4) The cost of cffDNA was a major factor in decision-making based on sensitivity analysis. When the price went down to ￥1 075, the incremental cost of strategy Ⅱ-1 was the lowest (￥757 000). If it further lowered to ￥697, strategy Ⅰ-2 was optimal (lower than ￥523 000). (5) The sensitivity analysis also suggested that the acceptance rate of cffDNA testing had no influence on the incremental cost-related findings (incremental cost: in strategy Ⅱ-7 was least and less than costs for one Down Syndrome patient). When the acceptance rate of prenatal diagnostic testing was lower than 80%, the incremental cost of strategy Ⅱ-7 (￥1.669 million) was the lowest, which was higher than raising a DS child.Conclusions:cffDNA testing in high-risk populations (strategyⅠ-1) could significantly reduce unnecessary diagnostic tests and is appropriate in total cost, cost-effectiveness and cost-benefit analysis, but misses more DS livebirths. Implementing prenatal diagnostic testing among pregnancies with risk cut-offs higher than 1/300 (strategy Ⅱ-7) could improve screening efficiency and reduce incremental costs, but require more cases to be tested. The cost of cffDNA testing is the most important influencing factor. On the premise of achieving substantial screening efficiency, strategy Ⅱ-1 and Ⅰ-2 are optimal with the lowest incremental costs if cffDNA testing cost drops to ￥1 075 and ￥697, respectively. Lower acceptance of prenatal diagnostic testing is accompanied by less detected DS cases and increased incremental costs than the baseline, which is not conducive to the prevention of birth defects.