Downregulated FGFR3 Expression Inhibits In Vitro Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells of Mice with TBXT Gene Mutation.

We studied the effect of fibroblast growth factor receptor 3 (FGFR3) inhibitor BGJ-398 on the differentiation of bone marrow mesenchymal stem cells (BM MSC) into osteoblasts in wild type (wt) mice and in animals with mutation in TBXT gene (mt) and possible differences in the pluripotency of these cells. Cytology tests showed that the cultured BM MSC could differentiate into osteoblasts and adipocytes. The effect of different BGJ-398 concentrations on the expression of FGFR3, RUNX2, SMAD1, SMAD4, SMAD5, SMAD6, SMAD7, and SMAD8 were studied by quantitative reverse transcription PCR. The expression of RUNX2 protein was evaluated by Western blotting. BM MSC of mt and wt mice did not differ in pluripotency and expressed the same membrane marker antigens. BGJ-398 inhibitor reduced the expression of FGFR3 and RUNX2. In BM MSC from mt and wt mice have similar gene expression (and its changing) in FGFR3, RUNX2, SMAD1, SMAD4, SMAD5, SMAD6, SMAD7, and SMAD8 genes. Thus, our experiments confirmed the effect of decreased expression of FGFR3 on osteogenic differentiation of BM MSC from wt and mt mice. However, BM MSC from mt and wt mice did not differ in pluripotency and are an adequate model for laboratory research.

[Analysis of pregnancy-related adverse outcomes in patients with severe hypothyroidism during pregnancy].

Objective: To analyze the pregnancy-related adverse outcomes in patients with severe hypothyroidism during pregnancy. Methods: Using cross-sectional study, a total of 47 pregnant women with severe hypothyroidism in the Peking University First Hospital from January 2007 to December 2020 were retrospectively collected by electronic case system. According to the occurrence of adverse pregnancy events (defined as any pregnancy complication or adverse maternal-fetal/neonatal outcomes), the patients were divided into pregnancy-related adverse outcomes group (n=33) and no pregnancy-related adverse outcomes group (n=15). The demographic data, thyroid function and thyroid autoantibody levels during pregnancy, pregnancy complications and maternal-fetal/neonatal outcomes of the two groups were recorded and analyzed. Results: The age of severe hypothyroidism women was (30.5±4.1) years. The median of gestational week at delivery was 38.6 (36.3, 39.9) weeks, the median of gestational week for diagnosis was 7.0 (6.0, 8.8) weeks, the median of the highest TSH level was 32.7(23.1,60.2)mU/L and the period of reaching the target TSH level for the first time was 6.0(4.0, 10.0)weeks. Most cases (82.5%, 33/40) had thyroid autoimmunity. All women were treated with levothyroxine (L-T4) during pregnancy. A total of 37 cases (77.1%, 37/48) of them obtained the recommended target values. Fourty cases (83.3%, 40/48) gave birth. The birth weight of newborns was (3 041±452) g, the body length was (49.4±2.1) cm, and the head circumference was (33.6±0.7) cm. The period of reaching to target TSH level for the first time in patients without pregnancy-related adverse outcomes was shorter [5.0 (3.0, 9.0) vs 8.0 (4.5, 12.5) weeks) ] (P=0.033), and the times of thyroid function monitoring were more frequent [ (8.2±3.5) vs (6.0±3.6) times] (P=0.049) than the group with pregnancy-related adverse outcomes. Conclusions: The incidence of pregnancy complications and adverse maternal-fetal/neonatal outcomes is high in patients with severe hypothyroidism during pregnancy. Intense follow-up, treatment and restoration of euthyroidism as prompt as possible may improve pregnant outcomes.

[Comparison of clinical features in antepartum and postpartum HELLP syndrome].

Objective: To analyze the clinical features and pregnancy outcomes in antepartum and postpartum hemolysis, elevated live enzymes, and low platelet count syndrome(HELLP syndrome). Methods: A retrospective study was conducted to collect maternal and neonatal information of pre-eclampsia complicated with HELLP syndrome in Peking University First Hospital during the ten years from April 2009 to March 2019. A total of 83 pregnant women were included according to the Tennessee Classification System. They were then allocated into two groups based on the onset time of HELLP syndrome: antepartum HELLP syndrome group (n=70) and postpartum HELLP syndrome group (n=13). The clinical features, symptoms, laboratory biomarkers, and pregnancy outcomes were compared between the two groups. Results: Among the 83 pregnant women with HELLP syndrome, 70 occurred prenatally (84%, 70/83) and 13 occurred postpartum (16%, 13/83). The twin or triplet pregnancy rate in the postpartum HELLP syndrome group was significantly higher than that in the antepartum HELLP syndrome group [6/13 vs 6% (4/70), P=0.001]. The gestational weeks for HELLP onset and delivery in the postpartum HELLP syndrome group were significantly later than those in the antepartum HELLP syndrome group [(35.8±3.0) vs (31.5±5.2) weeks, P=0.025; (36.7±2.3) vs (32.2±5.0) weeks, P=0.002]. The incidence of early-onset pre-eclampsia in the antepartum HELLP syndrome group was significant higher than that in the postpartum HELLP syndrome group [64% (45/70) vs 2/13, P=0.002]. The quantitative of 24-hour proteinuria was significant higher in the antepartum HELLP syndrome group than that in the postpartum HELLP syndrome group [(4.8±5.1) vs (1.8±1.6) g, P=0.002]. But there were no statistical significances in the comparison of other laboratory test indexes (all P>0.05). There were no significant differences between the two groups in clinical symptoms, severe maternal complications, transfusion or adverse maternal outcomes (all P>0.05). Conclusions: Antepartum and postpartum HELLP syndrome have similar clinical symptoms and laboratory characteristics. Both antepartum and postpartum HELLP syndrome could lead to severe maternal complications, which should be paid special attention in clinical practice, especially to the postpartum HELLP syndrome.

[Investigation and analysis of the implementation status of "Diagnosis and therapy guideline of preterm birth (2014)"].

Objective: To understand the actual situation of the implementation of "Diagnosis and therapy guideline of preterm birth（2014）", "Guideline" for short, by front-line obstetricians, and to provide reference for the further update and supplement of the "Guideline". Methods: This study designed a structured questionnaire for the prominent problems in the prevention and treatment of preterm birth, which was determined by the expert team drafting the "Guideline". In October to November 2021, a cross-sectional survey was conducted among obstetricians, including members of the Perinatal Medicine Branch of Jiangsu Medical Association and the Obstetrics Subgroup,Chinese society of Obstetrics and Gynecology, Chinese Medical Association, on the implementation status of the "Guideline". The recommendations of the "Guideline" were used as standard answers to determine the implementation rate. A total of 328 valid questionnaires were collected. The total score of the questionnaire was 12 points. The questionnaire was divided into low executive ability group (<7 points) and high executive ability group (≥7 points) with a score of 7 as the threshold value, and the differences in baseline information such as hospital grade and professional title between the two groups were compared. Results: The score of 328 obstetricians was (7.6±1.6) points, including 250 (76.2%, 250/328) in the high execution group and 78 (23.8%, 78/328) in the low execution group. The execution rates of "the use of uterine contraction inhibitors for short courses"[97.0% (318/328)], "late umbilical cord breakage after birth of premature infants"[87.8% (288/328)] and "should preterm patients with intact membranes be treated with antibiotics"[86.6% (284/328)] were all over 80%, indicating good implementation. Multiple logistic regression analysis showed that hospital grade and professional title were independent factors influencing the performance of the "Guideline"(all P<0.05), and secondary hospitals had lower scores and worse execution than tertiary hospitals (OR=0.42, 95%CI: 0.23-0.77; P=0.005). Senior titles had higher scores and better execution than junior titles (OR=5.33, 95%CI: 2.35-12.07; P<0.001). When answering the question "gestational week at which premature infants could survive in your hospital", only 3.4% (11/328) answered 22 weeks, and 44.5% (146/328) answered 28 weeks, accounted for the highest proportion. The gestational week of surviving premature infants in tertiary hospitals was earlier than that in secondary hospitals (P<0.05). The gestational week of surviving premature infants answered by senior titles was earlier than that of junior titles (P<0.05). Conclusions: Obstetricians generally have a good implementation of the "Guideline", and their understanding of some recommended clauses in the guidelines needs to be improved. In the future, training of primary hospitals and physicians with junior titles should be strengthened.

[Exploration on appropriate fetal weight of twin pregnancies at different gestational weeks and pregnancy complications and outcomes].

Objective: To explore the appropriate fetal weight of twin pregnancies at different gestational weeks and the association with pregnancy complications and outcomes. Methods: Fetal weight at different gestational weeks and related pregnancy complications and outcomes from 1 225 twin pregnancies, who gave birth at Peking University First Hospital from January 2004 to December 2020, were analyzed in this study, including hypertensive disorders in pregnancy, gestational diabetes mellitus (GDM), fetal growth restriction (FGR), fetal distress, preterm birth and neonatal asphyxia. The appropriate fetal weight of twin pregnancies at different gestational weeks were analysed based on the information from 616 twin pregnancies without complications (except preterm birth), and were expressed as P10~P90. The chi-square test was used to compare the risk of pregnancy complications and adverse outcomes in large for gestational age (LGA), appropriate for gestational age (AGA) and small for gestational age (SGA) twin pregnancies and the difference in incidence of pregnancy complications and adverse outcomes in different years. Results: The appropriate fetal weights of normal twin pregnancies at 28 to 37 weeks and 38-40 weeks of gestation were 910-1 255 g, 996-1 518 g, 1 105-1 785 g, 1 295-1 825 g, 1 336-2 000 g, 1 754-2 321 g, 1 842-2 591 g, 1 913-2 615 g, 2 150-2 847 g, 2 350-3 130 g and 2 450-3 250 g, respectively. The incidences of hypertensive disorders in pregnancy, FGR, fetal distress and neonatal asphyxia related to SGA twin pregnancies were significantly higher than AGA twin pregnancies (all P<0.05). The incidence of GDM in twin pregnant from 2017 to 2020 was higher than that from 2004 to 2009 or from 2010 to 2016, but the incidence of fetal distress and neonatal asphyxia were lower than those from 2010 to 2016, and the differences were statistically significant (all P<0.05). Conclusions: The appropriate weights of twin fetuses at different gestational weeks are different from singleton. The incidence of pregnancy complications and adverse outcomes in AGA fetuses is significantly lower than that in SGA fetuses under the specific weight standard for twin fetuses, which could provide a practical basis for clinical management of twin pregnancy.

[Prediction and analysis of adverse pregnancy outcomes in pregnant women with cesarean scar diverticulum].

Objective: To investigate the pregnancy outcomes of pregnant women with cesarean scar diverticulum (CSD) and to find the relevant factors that predict the occurrence of adverse pregnancy outcomes. Methods: From January 2015 to March 2019, 501 singleton pregnant women with a history of cesarean section who underwent regular prenatal examination in early pregnancy and eventually delivered in Peking University First Hospital were prospectively collected. According to the presence or absence of CSD in the first trimester of pregnancy, the pregnant women were divided into the CSD group (n=127, 25.3%) and the non-CSD group (n=374, 74.7%). According to the mode of delivery and the classification of the lower uterine segment seen during cesarean section, the CSD group was further divided into the non-rupture group (including spontaneous delivery and lower uterine segment grade Ⅰ;n=108, 85.0%) and rupture group (including lower uterine segment grade Ⅱ-Ⅳ;n=19, 15.0%). The general clinical data, pregnancy outcomes, diverticulum-related indexes [including length, width, depth (D), average diameter, volume, and residual myometrial thickness (RMT)] were compared. The predictive values of D/adjacent myometrial thickness≥50%, RMT≤2.2 mm and D/RMT>1.3 for uterine rupture in CSD pregnant women were verified. Results: (1) Comparison between CSD group and non-CSD group: the lower uterine segment thickness in the third trimester of pregnancy in the CSD group was lower than that in the non-CSD group [(1.2±0.5) vs (1.4±0.6) mm, respectively], and the incidence of uterine rupture was higher than that in the non-CSD group [15.0% (19/127) vs 8.0% (30/374), respectively], and the differences were statistically significant (both P<0.05). There were no significant differences in other clinical data and pregnancy outcomes between the two groups (all P>0.05). (2) Comparison of rupture group and non-rupture group: the lower uterine segment thickness in the third trimester of pregnancy in rupture group [(0.6±0.5) mm] was lower than that in non-rupture group [(1.2±0.6) mm], and the difference was statistically significant (t=3.486, P=0.001). There were no significant differences in diverticulum-related indexes between the two groups (all P>0.05). (3) Relationship between high risk predictors of uterine rupture and actual uterine rupture: the sensitivity of D/adjacent muscle thickness ≥50%, RMT≤2.2 mm and D/RMT>1.3 in predicting the high risk of uterine rupture were 94.7%, 57.9% and 73.6%, the specificity were 12.0%, 40.7% and 24.1%, the positive predictive value were 15.9%, 14.7%, 14.6%, and the negative predictive value were 92.8%, 84.6%, 83.9%, respectively. Conclusions: The risk of uterine rupture in pregnant women with CSD is higher than that in those without CSD. There is no significant correlation between CSD related indexes and uterine rupture in the first trimester. Monitoring the lower uterine segment thickness in the third trimester might be helpful to predict the occurrence of adverse pregnancy outcomes.

[Value of serum YKL-40 in the diagnosis of anti-MDA5-positive patients with dermatomyositis complicated with severe pulmonary injury].

OBJECTIVE: To investigate the value of serum and bronchoalveolar lavage fluid (BALF) chitinase-3-like-1 protein (YKL-40) in the diagnosis of anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (DM) patients complicated with serious pulmonary injury, including rapidly progressive interstitial lung disease (RP-ILD) and pulmonary infection. METHODS: Anti-MDA5 antibodies positive patients with DM who were hospitalized in the Department of Rheumatology of China-Japan Friendship Hospital from 2013 to 2018 were involved in this study. Demographic information, clinical, laboratory and imaging data were retrospectively collected. ELISA was used to detect the serum and BALF levels of YKL-40. The receiver operating characteristic (ROC) curve was drawn, and the area under ROC curve (AUC) was used to evaluate the diagnostic value of serum YKL-40 for pulmonary injury.Interstitial lung disease (ILD) was confirmed by chest high-resolution CT (HRCT). RP-ILD was defined as progressive respiratory symptoms such as dyspnea and hypoxemia within 3 months, and/or deterioration of interstitial changes or appearace of new pulmonary interstitial lesions on chest HRCT. Pulmonary infection was considered as positive pathogens detected in qualified sputum, blood, bronchoalveolar lavage fluid or lung biopsy specimens. RESULTS: A total of 168 anti-MDA5-positive DM patients including 108 females and 60 males were enrolled in the study. Of these patients, 154 had ILD, and 66(39.3%) of them presented RP-ILD. Seventy patients with pulmonary infection were confirmed by etiology. In the patients with RP-ILD, 39 (59.1%) of them were complicated with pulmonary infection. While only 31 cases(30.4%) had pulmonary infection in the non-RP-ILD patients. The incidence of pulmonary infection in the patients with RP-ILD was significantly higher than that of those with non-RP-ILD (P < 0.001). The serum YKL-40 levels in the RP-ILD patients with pulmonary infection were the highest compared with RP-ILD without pulmonary infection, non-RP-ILD with pulmonary infection and non-RP-ILD without pulmonary infection groups among all the patients [83 (42-142) vs. 42 (21-91) vs. 43 (24-79) vs. 38 (22-69), P < 0.01].The sensitivity, specificity and AUC of serum YKL-40 in the diagnosis of RP-ILD complicated with pulmonary infection were 75%, 67%, and 0.72, respectively. The AUC of diagnosed of anti-MDA5 positive DM patients complicated with RP-ILD and pulmonary infection was higher than that of patients complicated with only RP-ILD and only pulmonary infection (0.72 vs. 0.54 and 0.55, Z=2.10 and 2.11, P < 0.05). CONCLUSION: The prognosis of anti-MDA5-positive DM patients with RP-ILD and pulmonary infection were poor. Serum YKL-40 level can be used as a helpful tool for the diagnosis of coexistence of these conditions in the patients.

[Gender differences in risk factors and characteristics of young patients hospitalized for first acute coronary syndrome].

Objective: To analyze the characteristics of modifiable risk factors, coronary artery lesions, reperfusion and drug treatment in young women hospitalized for first acute coronary syndrome (ACS). Methods: Clinical data of young adults of 18 to 44 years hospitalized for first ACS in Beijing Anzhen Hospital between January 2007 and December 2017 were analyzed. A total of 7 106 young adults with ACS were enrolled, 6 593(92.8%) were male and 513(7.2%) were female. There were 2 254(31.7%) patients with ST-segment elevation myocardial infarction (STEMI), 704(9.9%) patients with non-ST-segment elevation myocardial infarction (NSTEMI) and 4 148(58.4%) patients with unstable angina (UA). Clinical characteristics, laboratory examinations, coronary angiography and medical treatment were recorded. The gender differences in the characteristics of modifiable risk factors and coronary artery stenosis in young patients with ACS were also analyzed. Results: Dyslipidemia (87.5%) followed by overweight/obese(83.8%) and smoking (68.5%) were most prevalent modifiable risk factors in men. Dyslipidemia (63.4%), overweight/obese (63.4%) and hypertension (45.5%) were most prevalent modifiable risk factors in women. The prevalence rates of at least 1 risk factor in men and women patients were 99.1% and 87.9%, respectively. Between 2007 and 2017, the rates of hypertension and overweight/obese in men increased, and the rates of dyslipidemia and smoking decreased (trend P<0.01). The changes of incidence of modifiable risk factors through the years in women were not statistically significant. The rate of men receiving coronary angiography was higher than that in women (96.6% vs 93.4%, P<0.01). Women were more likely to suffer left main coronary artery disease than men (7.3% vs 4.1%, P<0.01). Multi-vessel coronary artery disease occurred more in men (43.4%), and single vessel coronary artery disease occurred more in women (47.0%). Women presented with STEMI had a lower probability of receiving clopidogrel/ticagrelor (76.8% vs 86.1%, P<0.01) and angiotensin Ⅰ-converting enzyme inhibitor/angiotonin receptor blocker (ACEI/ARB) (46.5% vs 60.2%, P<0.01) than that in men. Women presented with UA had a lower probability of receiving aspirin (86.3% vs 89.9%), clopidogrel/ticagrelor (69.7% vs 75.6%), statin (78.8% vs 85.0%) and ACEI/ARB (32.7% vs 38.6%) than men (all P<0.01). Women had a higher probability of presenting Killip II-IV than men (38.6% vs 25.6%, P<0.05). Conclusion: The majority of young patients with ACS were men. The prevalence rates of modifiable risk factors are very high in both man and woman. Compared with man, women with AMI are more likely to develop acute heart failure with lower probability of reperfusion and drug treatment.

[Effect and mechanism of TNF-α and etanercept on the invasion ability of extravillous trophoblast cell in URSA patients].

Objective: To investigate the effect and mechanism of tumor necrosis factor α (TNF-α) and its inhibitor etanercept (ETA) on the invasion ability of extravillous trophoblast in patients with unexplained recurrent spontaneous abortion (URSA). Methods: (1) Patients were collected from March to June in 2019. They were divided into the URSA group (n=15) and the normal control group (n=15), according to whether diagnosed with URSA or not. The mRNA expression levels of TNF-α in villi tissue of patients in the two groups were detected by quantitative real-time PCR (qRT-PCR). (2) The mRNA and protein expression levels of matrix metalloproteinase-2 (MMP-2), Slug and CXC chemokine rceptor 4 (CXCR4) in HTR-8/SVneo cells were detected by qRT-PCR or western blot after being stimulated by exogenous TNF-α (0.2, 2, 20 ng/ml) alone or TNF-α along with ETA, or phosphate buffered saline (PBS) as control. (3) The invasion ability of HTR-8/SVneo cells was investigated by transwell test after stimulating by TNF-α alone or TNF-α along with ETA. (4) The mRNA and protein expression levels of MMP-2, Slug and CXCR4 in HTR-8/SVneo cells, which were stimulated by TNF-α (2 ng/ml) alone after nuclear factor-κB (NF-κB) inhibitor, BAY 11-7028, preconditioning, were detected by qRT-PCR or western blot. Results: (1) The mRNA expression level of TNF-α in villi tissue of URSA group (4.10±0.49) was 4.1 times as much as the normal control group (t=10.51, P<0.05). (2) The mRNA and protein expression levels of MMP-2, Slug and CXCR4 in HTR-8/SVneo cells of TNF-α group were significantly lower than those in PBS control group (P<0.05) and those in TNF-α along with ETA group (P<0.05). (3) The invasion ability of HTR-8/SVneo cells in TNF-α group was significantly decreased than PBS group and TNF-α along with ETA group (78±14 vs 373±26 vs 227±44, P<0.05). (4) The mRNA and protein expression levels of MMP-2, Slug and CXCR4 in HTR-8/SVneo cells with BAY 11-7028 preconditioning (mRNA: 1.03±0.10, 1.03±0.06, 1.09±0.08; protein: 1.09±0.03, 1.49±0.03, 1.12±0.03) were significantly higher than without preconditioning after being stimulated by TNF-α (all P<0.05). Conclusions: The expression of TNF-α in the villi of URSA patients is much higher than normal early pregnant women. TNF-α could decrease the capacity of invasion by suppressing the expression of MMP-2, Slug and CXCR4 through NF-κB signaling pathway in extravillous trophoblast cells. While ETA could improve the invasiveness capability of extravillous trophoblast cells through inhibiting the negative effect of TNF-α.

[Effect of placenta previa attached to cesarean scar for adverse pregnant outcomes in patients with placenta accreta spectrum disorders].

Objective: To investigate the effect of placenta previa attached to cesarean scar for adverse pregnant outcomes in patients with or without placenta accreta spectrum disorders (PAS). Methods: The clinical information of patients with cesarean section history and placenta previa during the perioperative period at Peking University First Hospital from January 1st, 2015 to December 31st, 2020 were collected retrospectively. There were 53 cases without PAS and 172 cases with PAS, 153 cases with abnormally invasive placenta (containing placenta increta and placenta percreta) and 72 cases without PAS or with placenta accreta. The pregnant outcomes including rate of postpartum hemorrhage, transfusion, hysterectomy between the above groups were compared. Multivariate analysis was performed to study the factors significantly associated with PAS. Results: Pregnant women with PAS were at higher risk of adverse pregnant outcomes than those without PAS. Patients with PAS had higher incidences of hysterectomy [12.2% (21/172) vs 0(0/53); P=0.005], postpartum hemorrhage [60.5% (104/172) vs 5.7% (3/53); P<0.01] and blood transfusion [66.9% (115/172) vs 7.5% (4/53); P<0.01]. In the subgroup analysis stratified by the type of PAS, patients with abnormally invasive placenta were at higher risk of hysterectomy [13.7% (21/153) vs 0 (0/72); P<0.01], postpartum hemorrhage [66.7% (102/153) vs 6.9% (5/72); χ²=70.873, P<0.01] and blood transfusion [74.5% (114/153) vs 6.9% (5/72); χ²=90.869, P<0.01]. After multiple logistic regression, the type of creta had the positive relation with postpartum hemorrhage (OR=27.622, 95%CI:9.873~77.280; P<0.01) and blood transfusion (OR=36.912, 95%CI:13.239~102.922; P<0.01). There were no significant correlations between adverse pregnant outcomes and the type of placenta previa or the times of cesarean section (all P>0.01). Conclusions: Placenta previa attached to cesarean scar without PAS or with placenta accreta could not act as the factor of predicting adverse pregnant outcomes in clinic. Placenta previa attached to cesarean scar with placenta increta or placenta percreta could increase the risk of adverse pregnant outcomes.

[Clinical outcomes and influence factors of 435 singleton pregnancies with short cervix].

Objective: To investigate the clinical outcomes of different treatment options on singleton short cervix and its influence factors. Methods: Totally 435 cases of singleton pregnancies who were diagnosed with short cervix (≤25 mm) between 12 to 33+6 gestational weeks in Peking University First Hospital from January 2018 to December 2018 were enrolled, including 21 cases with cervical length <10 mm, 414 cases with cervical length between 10 to 25 mm. The onset time was <24 gestational weeks in 106 cases, while 104 cases were at 24-29+6 gestational weeks and 225 cases of ≥30 gestational weeks. Gestational outcomes including delivery before 37 weeks, delivery before 34 weeks, neonatal birth weight (NBW) and adverse neonatal outcome (ANO) were compared among three treatment groups: rest group, progesterone group and cerclage group. Influence factors were also investigated. Results: (1) The incidence of short cervix in pregnancy was 7.07% (435/6 155), while 106 cases were at <24 gestational weeks (1.72%, 106/6 155), 104 cases (1.69%, 104/6 155) at 24-29+6 gestational weeks and 225 cases (3.66%, 225/6 155) at ≥30 gestational weeks. (2) In the group of cervical length <10 mm, rate of delivery before 37 and 34 weeks were 62% (13/21) and 57% (12/21) respectively. One case of progesterone treatment underwent miscarriage. Compared with rest group (n=8), delivery weeks [28.5 (25.0-40.0) vs 37.0 (28.0-40.0), P=0.020] and NBW [1 245 g (630-3 830 g) vs 2 648 g (1 560-3 830 g), P=0.028] were higher in cerclage group (n=9), while ANO was not statistically different (P>0.05). (3) In the group of cervical length ≥10 mm before 24 gestational weeks, the delivery weeks, incidence of delivery before 34 weeks, adjusted incidence of delivery before 37 weeks, NBW and ANO were not statistically different (P>0.05) among rest group (n=36), progesterone group (n=26) and cerclage group (n=34). In vitro fertilization (OR=11.97, 95%CI: 1.88-76.44, P=0.009), infection (OR=46.03, 95%CI: 5.12-413.58, P=0.001), sludge on sonography (OR=9.87, 95%CI: 1.69-57.60, P=0.011) and history of short cervix (OR=7.24, 95%CI: 1.04-50.24, P=0.045) were independent risk factors of preterm birth. (4) In the group of cervical length ≥10 mm and gestational weeks between 24-29+6, the delivery weeks, incidence of delivery before 37 weeks, incidence of delivery before 34 weeks, NBW and ANO were not statistically different (P>0.05) among rest group (n=52), progesterone group (n=34) and cerclage group (n=9). Infection was an independent risk factor of preterm birth (OR=56.40, 95%CI: 4.67-680.61, P=0.002). (5) Outcomes of 223 cases were relatively good in the group of cervical length ≥10 mm beyond 30 gestational weeks. The incidence of delivery before 34 weeks was 6.3% (14/223). The delivery weeks, incidence of delivery before 37 and 34 weeks, NBW and ANO were not statistically different (P>0.05) among 3 groups. Infection (OR=10.91, 95%CI: 2.21-53.96, P=0.003) and history of preterm birth (OR=8.63, 95%CI: 1.25-59.65, P=0.029) were independent risk factors of preterm birth. Conclusions: Short cervix is a common complication of pregnancy. Cervical cerclage is related with better outcome for patients with cervical length <10 mm. Neither progesterone nor cervical cerclage improves pregnancy outcome for >10 mm cervical length patients comparing with rest. Infection, sludge, in vitro fertilization, history of short cervix and history of preterm birth are independent risk factors of preterm birth in short cervix pregnancies.

[Effects of interpregnancy interval on pregnancy outcomes of subsequent pregnancy: a multicenter retrospective study].

Objective: To explore the effects of interpregnancy interval (IPI) on pregnancy outcomes of subsequent pregnancy. Methods: A multicenter retrospective study was conducted in 21 hospitals in China. Information of age, height, pre-pregnancy weight, IPI, history of diseases, complications of pregnancy, gestational age of delivery, delivery mode, and pregnancy outcomes of the participants were collected by consulting medical records of pregnant women who had two consecutive deliveries in the same hospital during 2011 to 2018. The participants were divided into 4 groups according to IPI:<18 months, 18-23 months, 24-59 months and ≥60 months. According to the WHO's recommendation, with the IPI of 24-59 months group as a reference, to the effects of IPI on pregnancy outcomes of subsequent pregnancy were analyzed. Stratified analysis was further carried out based on age, history of gestational diabetes mellitus (GDM), macrosomia, and premature delivery, to explore the differences in the effects of IPI on pregnancy outcomes among women with different characteristics. Results: A total of 8 026 women were included in this study. There were 423, 623, 5 512 and 1 468 participants in <18 months group, 18-23 months group, 24-59 months group and ≥60 months group, respectively. (1) The age, pre-pregnancy body mass index (BMI), history of cesarean section, GDM, gestational hypertension and cesarean section delivery rate of <18 months group, 18-23 months group, 24-59 months group and ≥60 months group were gradually increased, and the differences were statistically significant (P<0.05). (2) After adjusting for potential confounding factors, compared with women in the IPI of 24-59 months group, the risk of premature delivery, premature rupture of membranes, and oligohydramnios were increased by 42% (OR=1.42, 95%CI: 1.07-1.88, P=0.015), 46% (OR=1.46, 95%CI: 1.13-1.88, P=0.004), and 64% (OR=1.64, 95%CI: 1.13-2.38, P=0.009) respectively for women in the IPI≥60 months group. No effects of IPI on other pregnancy outcomes were found in this study (P>0.05). (3) After stratified by age and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of oligohydramnios for women with advanced age (OR=2.87, 95%CI: 1.41-5.83, P=0.004); and <18 months could increase the risk of premature rupture of membranes for women under the age of 35 (OR=1.59, 95%CI: 1.04-2.43, P=0.032). Both the risk of premature rupture of membranes (OR=1.58, 95%CI: 1.18-2.13, P=0.002) and premature delivery (OR=1.52, 95%CI: 1.07-2.17, P=0.020) were significantly increased in the IPI≥60 months group. After stratified by history of GDM and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would lead to an increased risk of postpartum hemorrhage for women with a history of GDM (OR=5.34, 95%CI: 1.45-19.70, P=0.012) and an increased risk of premature rupture of membranes for women without a history of GDM (OR=1.44, 95%CI: 1.10-1.90, P=0.009). After stratified by history of macrosomia and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months could increase the proportion of cesarean section for women with a history of macrosomia (OR=4.11, 95%CI: 1.18-14.27, P=0.026) and the risk of premature rupture of membranes for women without a history of macrosomia (OR=1.46, 95%CI: 1.12-1.89, P=0.005). After stratified by history of premature delivery and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of premature rupture of membranes for women without a history of premature delivery (OR=1.47, 95%CI: 1.13-1.92, P=0.004). Conclusions: Both IPI≥60 months and <18 months would increase the risk of adverse pregnancy outcomes in the subsequent pregnancy. Healthcare education and consultation should be conducted for women of reproductive age to maintain an appropriate IPI when they plan to pregnant again, to reduce the risk of adverse pregnancy outcomes in the subsequent pregnancy.

[Clinical characteristics and prognosis of young (<35 years) patients with acute ST-segment elevation myocardial infarction].

Objective: To analyze the risk factors and clinical characteristics as well as long-term prognosis of young patients (aged 18-35 years) with acute ST-segment elevation myocardial infarction (STEMI). Methods: In this retrospective study, from January 2007 to December 2017, STEMI patients who were hospitalized in Beijing Anzhen Hospital, Capital Medical University and younger than 45 years old were collected. Patients were divided to the 18-35 years old group and 36-44 years old group. The basic information of patients, clinical laboratory results, surgical information and discharge diagnosis of enrolled patients were extracted from the electronic medical record system. Subgroup analysis on STEMI patients aged 18 to 35 years was performed to compare the clinical features and outcome of patients with normal coronary angiography or stenotic coronary angiography. Results: 496 patients (20.3%) were between 18 and 35 years old, 480 cases (96.8%) were men, and 371 cases (74.8%) were smokers. The proportion of hypertension and diabetes was lower, but percent of obese (122 cases (43.3%)), level of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), uric acid and homocysteine ​​(Hcy) were significantly higher in patients aged 18 to 35 years compared with STEMI patients aged 36 to 44 years (all P<0.05). In the 18-35 years old group, there were 53 patients (10.7%) with normal coronary angiography and 443 patients (89.3%) with stenosis. The age, proportion of hypertension and diabetes, TC, LDL-C, and triglyceride (TG) levels were lower in the normal coronary angiography group than those in the coronary artery stenosis group (all P<0.05). The main coronary artery lesions were single vessel lesions (263 cases (59.4%)), and the main culprit vessels were left anterior descending artery lesions (238 cases (53.7%)). The follow-up time was 7.0 (4.0, 10.0) years, cardiovascular events were reported in 62 patients (18.9%), of which 14 patients (3.2%) died. The survival rate of patients without cardiovascular events in normal coronary angiography group was higher than that in stenosis group (P=0.029). Multivariate Cox regression analysis showed that diabetes (HR=2.713, 95%CI 1.479-4.976, P=0.001) and dyslipidemia (HR=2.819, 95%CI 1.564-5.079, P=0.001) were independent risk factors for recurrence of cardiovascular events in adult STEMI patients aged 18 to 35 years. Conclusions: STEMI patients aged 18 to 35 years were featured by male sex, obese and smokers. The proportion of hypertension and diabetes was low, while the levels of LDL-C, uric acid and Hcy were high in these patients. Coronary artery stenosis was common, and the stenosis was more likely to occur in the left anterior descending branch. Patients with normal coronary angiography had a better prognosis than those with stenosis. Diabetes and hyperlipidemia increased the risk of recurrent cardiovascular events.

[Difference on prevalence and trends of conventional risk factors for ASCVD between young Chinese and American adults with first acute myocardial infarction].

Objective: This study aimed to compare the prevalence and trends of conventional risk factors for atherosclerotic cardiovascular disease(ASCVD) between young Chinese and American adults with first acute myocardial infarction. Methods: This was a retrospective cohort analysis. Hospitalized yang adults (aged from 18 to 44 years old) with first acute myocardial infarction(AMI) from January 2007 through December 2017 were identified from Beijing Anzhen hospital medical record system. Prevalence and trends of hypertension, diabetes mellitus, obesity, smoking, and dyslipidemia were analyzed and compared with young American adults, whose data were reported by Yandrapalli et al, and the hospitalizations for a first AMI in young adults aged 18 to 44 years were identified from national inpatient sample from January 2005 through September 2015. Results: Chinese cohort included 2 866 young adults with a first AMI (male, n=2 739, female, n=127), the mean age was (39±5) years. Presentation of AMI was more frequently ST-segment elevation myocardial infarction (77.3%, 2 214/2 866). American cohort included 280 875 subjects (male, n=203 700, female, n=77 175), the mean age was 39±5 years. Presentation of AMI was more frequently non-ST-segment elevation myocardial infarction (53.6%, 150 549/280 875). In China, dyslipidemia 2 254 (78.6%), smoking 2 084(72.7%), and hypertension 1 170 (40.8%) were most prevalent, and 96.0% (2 752/2 866) of patients had at least 1 risk factor; in the United States, smoking 159 537(56.8%), dyslipidemia 145 212 (51.7%), and hypertension 139 876 (49.8%) were most prevalent, and 90.3% (253 630/280 875) of patients had at least 1 risk factor. Women had a prevalence of diabetes was higher in women, and prevalence of dyslipidemia and smoking was higher in men in China (all P<0.05);prevalence of obesity, diabetes and hypertension was higher in Women, and prevalence of dyslipidemia and smoking was higher in man in the United States (all P<0.001). Prevalence of dyslipidemia and smoking was higher Chinese men (79.3% vs. 54.6%, 75.5% vs. 58.1%,all P<0.001), and prevalence of obesity, diabetes and hypertension was lower (13.1% vs. 18.6%, 14.9% vs. 19.9%, 40.6% vs. 49.3%, all P<0.001)in Chinses cohort than those in the United States cohort. Prevalence of smoking and obesity was lower (12.6% vs. 53.4%, 10.2% vs. 26.9%, all P<0.001) and prevalence of dyslipidemia was higher (63.8% vs. 44.1% P<0.001) in Chinese women than those in the United States women. Patients presenting with non-ST-segment elevation myocardial infarction had a higher prevalence of obesity, diabetes and hypertension than patients presenting with ST-segment elevation myocardial infarction in China (20.1% vs.10.9%, 17.6% vs. 14.5%, 47.4% vs. 38.9%, all P<0.05). The prevalence of the three risk factors also was higher in patients presenting with non-ST-segment elevation myocardial infarction in the US (24.0% vs.17.0%, 25.0% vs. 20.0%, 54.6% vs. 44.2%, all P<0.001), prevalence of smoking and dyslipidemia was lower in these patients (53.5% vs. 60.5%,51.4% vs. 52.1%, all P<0.001). The prevalence of hypertension and obesity increased and the rate of smoking reduced in China from 2007 through 2017 (all trend P<0.001). The prevalence of all these five conventional risk factors increased temporally in the United States from 2005 to 2015 (all trend P<0.001). The prevalence of hypertension increased by 15.6% in China and 14.5% in the United States, respectively, accounting the largest increase. Conclusions: Smoking, dyslipidemia, and hypertension are most prevalent in China and United State. Significant sex and AMI subtype difference are observed for individual risk factors. The prevalence of hypertension and obesity increased significantly over time in China and all these five conventional risk factors increased significantly in the United States.

[Risk factor distribution features and trends of young adults with first acute coronary syndrome].

Objective: To observe the characteristics and trends during the last 11 years of risk factors of young adults with first acute coronary syndrome (ACS). Methods: It was a cross-sectional study. We included young adults (18 to 44 years old) hospitalized for acute coronary syndrome in Beijing Anzhen Hospital for a first time from January 2007 to December 2017. Acute coronary syndromes include ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), and unstable angina (UA). The general information, medical history and laboratory test were recorded. Risk factors of ACS were smoking, dyslipidemia, overweight/obesity, hypertension and diabetes. Results: Data from 7 106 patients were analyzed, mean age was (39.8±4.2) years old and 6 593(92.8%)were men, including 2 254 (31.7%) STEMI, 704 (9.9%) NSTEMI and 4 148 (58.4%) UA. Most patients were male (6 593(92.8%)). Dyslipidemia (85.8%(6 094/7 106)), overweight/obesity (82.3%(5 850/7 106)), and smoking (63.9%(4 545/7 106)) were most prevalent. 98.3% (6 885/7 106) patients had at least 1 risk factor. The prevalence of hypertension, diabetes and overweight/obesity increased from 2007 to 2017. Rates of hypertension increased from 37.1%(111/299) to 48.1%(498/1 035) (Ptrend<0.01), diabetes from 12.0%(36/299) to 19.4%(201/1 035) (Ptrend<0.01), overweight/obesity from 74.2%(222/299) to 83.9%(868/1 035) (Ptrend<0.05), respectively. Conclusions: Dyslipidemia, overweight/obesity and smoking are most prevalent risk factors in young adults with a first ACS and most patients have at least 1 risk factor for ACS. Rates of hypertension, diabetes and overweight/obesity progressively increases over time in this patient cohort.

Observation of Dynamical Quantum Phase Transitions with Correspondence in an Excited State Phase Diagram.

Dynamical quantum phase transitions are closely related to equilibrium quantum phase transitions for ground states. Here, we report an experimental observation of a dynamical quantum phase transition in a spinor condensate with correspondence in an excited state phase diagram, instead of the ground state one. We observe that the quench dynamics exhibits a nonanalytical change with respect to a parameter in the final Hamiltonian in the absence of a corresponding phase transition for the ground state there. We make a connection between this singular point and a phase transition point for the highest energy level in a subspace with zero spin magnetization of a Hamiltonian. We further show the existence of dynamical phase transitions for finite magnetization corresponding to the phase transition of the highest energy level in the subspace with the same magnetization. Our results open a door for using dynamical phase transitions as a tool to probe physics at higher energy eigenlevels of many-body Hamiltonians.

[Survey of related factors of maternal venous thromboembolism in nine hospitals of China].

Objective: To investigate and analyze disease status and risk factors of venous thromboembolism (VTE) during pregnancy and puerperium in our country. Methods: Clinical datas were collected from 575 patients diagnosed with VTE during pregnancy and puerperium and hospitalized in nine medical institutions in our country from January 1, 2015 to November 30, 2019, and retrospectively analyzed it's disease status and risk factors. Results: (1) The proportion of VTE in pregnancy and puerperium was 50.6% (291/575) and 49.4% (284/575), respectively. Four patients died, the mortality rate was 0.7% (4/575). The cause of death was pulmonary embolism. (2) The location of VTE during pregnancy and puerperium was mainly in the lower limb vascular (76.2%, 438/575), followed by pulmonary vessels (7.1%, 41/575). (3) In the risk factors of VTE, cesarean section accounted for 32.3% (186/575), maternal advance age accounted for 27.7% (159/575), braking or hospitalization during pregnancy accounted for 13.6% (78/575), other risk factors accounted for more than 5% were previous VTE, obesity, preterm birth, assistant reproductive technology conception and so on, pre-eclampsia and multiple pregnancy accounted for 4.9% (28/575) respectively. In addition, some patients with VTE did not have any of the above risk factors, and the incidence rate was as high as 23.1% (133/575). Conclusions: The occurrence of VTE during pregnancy and puerperium is related to multiple risk factors, and could lead to matemal death, It is very necessary to screen VTE risk factors for all pregnant women, to make corresponding prevention and control measures.

Clinical outcomes and predictive relapse factors of IgG4-related disease following treatment: a long-term cohort study.

OBJECTIVES: The aim of this study was to investigate the predictive factors for relapse of IgG4-related disease (IgG4-RD) and observe the long-term clinical outcomes in patients with IgG4-RD. METHODS: We included in the present analysis 122 patients who were newly diagnosed with IgG4-RD, treated with glucocorticoid (GC) monotherapy or GC and immunosuppressant combination therapy, and followed for at least 3 years. Clinical relapse, response and side effects were recorded. RESULTS: The cumulative relapse rates of patients in this study were 10.66%, 22.95% and 27.87% at 12, 24 and 36 months, respectively. Complete drug withdrawal was an independent risk factor for disease relapse. Higher serum IgG4 concentrations, involvement of more organs, higher IgG4 RI scores and elevation of eosinophils at baseline were closely associated with disease relapse. Re-elevation of serum IgG4 concentrations and low GC maintenance dosage during the follow-up period were significantly associated with clinical relapse. The GC dosage should be more than 6.25 mg day-1 as monotherapy during the maintenance stage; moreover, combining with immunosuppressants can reduce the GC dosage. Adding GC or immunosuppressants for patients with re-elevation of serum IgG4 levels could prevent later disease relapse. No serious complications were noted during long-term follow-up. CONCLUSIONS: The combination of GC with immunosuppressants was more effective than GC monotherapy during the steroid tapering and maintenance stages. Higher serum IgG4 levels, involvement of more organs, higher IgG4 RI scores, history of allergy, eosinophil elevation at baseline, re-elevation of serum IgG4 levels and lower GC maintenance dosage at follow-up might be predictive of relapse.

[Clinical and pathological characteristics of immune mediated necrotizing myopathy].

OBJECTIVE: To investigate the clinical and pathological features of immune-mediated necrotic myopathies (IMNM) with different myositis-specific antibodies (MSAs). METHODS: In the study, 104 IMNM patients who met any of the following three criteria were selected from idiopathic inflammatory myopathy patients who had MSAs results and underwent muscle biopsy from 2008 to 2018 in China-Japan Friendship Hospital: (1) Anti-signal recognition particle (SRP) antibody positive; (2) Anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) antibody positive; (3) MSAs negative and consistent with the pathological diagnostic criteria of IMNM defined by the European Neuromuscular Centre in 2004. The clinical, laboratory and muscle pathological information of the IMNM patients were retrospectively collected and compared in anti-SRP, anti-HMGCR and MSAs negative groups. RESULTS: Of 104 IMNM patients, 47 patients (45.2%) were positive for anti-SRP antibody, 23 (22.1%) were positive for anti-HMGCR antibody, and 34 (32.7%) were negative for MSAs. The common symptoms of IMNM patients were muscle weakness (92.3%), elevated serum creatine kinase level (92.3%), dysphagia (33.7%) and interstitial lung diseases (ILD) (49.5%). The anti-HMGCR-positive patients were more frequent to have "V" sign (30.4% vs. 4.3% and 5.9%, P<0.01) as compared with the anti-SRP-positive and MSAs-negative patients. The incidence of ILD in the anti-SRP-positive patients was higher than that in the anti-HMGCR-positive and MSAs negative patients (64.4% vs. 34.8% and 29.0%, P<0.01). The prevalence of the patients combined with other connective tissue diseases in MSAs-negative IMNM was higher than that in the other two groups (32.4% vs. 8.5% and 4.3%, P<0.01). 93.3% of the anti-SRP-positive patients were found with antinuclear antibody positivity, higher than those of the anti-HMGCR-positive and MSAs-negative patients (93.3% vs. 36.4% and 58.8%, P<0.001). The common pathological features of IMNM were muscle fibre necrosis (94.2%), regeneration (67.3%) and phagocytosis (65.4%), overexpression of major histocompatibility complex1 on sarcolemma (78.8%), infiltration of CD4+ T cells (81.7%) and CD68+ macrophage (79.8%) and expression of membrane attack complex (MAC) (77.8%). The endomysial infiltration of CD4+ T cells and CD68+ macrophage and MAC expression on sarcolemma in the MSAs-negative group were more common than that in the anti-SRP and anti-HMGCR groups (88.2% vs. 57.4% and 60.9%, 91.2% vs. 59.1% and 38.1%, 76.5% vs. 45.5% and 42.9%, respectively, P<0.01). CONCLUSION: There is heterogeneity in anti-SRP-positive, anti-HMGCR-positive or MSAs-negative patients. The detection of MSAs and performing of muscle biopsy are useful for distinguishing different types of IMNM.

[Analysis of genes related to hypothyroidism during pregnancy].

Objective: By comparing and analyzing the differential sites of single nucleotide polymorphisms (SNP) between pregnant women with hypothyroidism and normal controls, the possible pathogenesis of hypothyroidism during pregnancy was explored. Methods: A total of 53 pregnant women with hypothyroidism during pregnancy from January 2018 to October 2018 were enrolled. A total of 50 pregnant women who underwent concurrent delivery and matched age with the case group were selected. Whole blood scans were performed on blood samples from two groups of subjects using the Illumina ASA chip to analyze the SNP with significant differences between the two groups. The human genome database hg19_dbsnp_version150 was employed to locate related genes. The association of related genes with thyroid dysfunction and pregnancy complications were analyzed. Results: A total of 13 SNPs were found in the study: rs4668077 (P=2.87E-05) in CERS6, rs6717546 (P=5.92E-05) in UGT1A1, rs1965358(P=7.78E-05) in CASR, rs916801 (P=9.22E-05) near CXCL14, rs6886845 (P=8.67E-05)near MAT2B, rs76245053 in GRIK2 (P=2.07E-05), rs6977642 (P=2.10E-05)in HDAC9, rs6949597 (P=3.68E-05) near ATXN7L1, rs11186331 (P=2.08E-05) in HTR7, rs2415551 (P=4.53E-05) near FBXO33, rs75850124 (P=9.24E-05) and rs76519339 (P=9.24E-05)in MIR4527, rs1014971 (P=3.24E-05) near CBX6 were statistically significant in the hypothyroidism group compared with the control group. Conclusions: The related gene UGT1A1 is related to the metabolism of thyroxine in the liver. CASR, CXCL14 and CBX6 are related to reproductive ability. CXCL14, CASR, HBAC9 and CERS6 are related to metabolic syndrome, and GRIK2, HTR7 and FBOX33 are related to neuropsychiatric diseases. Abnormal serum thyroxine levels during pregnancy may be associated with abnormal metabolism of thyroxine caused by UGT1A1 mutation. Genes associated with reproduction, metabolism, and neuropsychiatric disorders suggest a pathogenic link between hypothyroidism and infertility, metabolic syndrome, and neuropsychiatric disorders.