Objective:To explore and compare the reference ranges of four coagulation tests in normal pregnant women during early and late pregnancy and the influence of age.Methods:Values of four coagulation tests from 4 974 pregnant women, who gave single birth at Peking University First Hospital, Obstetrics and Gynecology Hospital of Fudan University, West China Second University Hospital, Peking University Third Hospital and Shengjing Hospital of China Medical University from February 2017 to July 2020, were measured and analyzed in this study, including prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib) and thrombin time (TT). The four normal reference ranges of coagulation during early and late pregnancy phases were expressed as P2.5- P97.5. The difference of two pregnancy phases was compared by non-parametric test of two related samples. And the difference between pregnant women of advanced and non-advanced age in the same pregnancy phase was compared by independent sample non-parametric test. Chi-square test was used to compare the incidence of pregnancy complications in different coagulation reference ranges. Results:The reference ranges of PT of normal pregnant women′s early and late pregnancy were 10.0-13.9 s and 9.6-12.3 s, the reference ranges of APTT were 22.6-35.3 s and 22.4-30.9 s, the reference ranges of Fib were 2.4-5.0 g/L and 3.0-5.7 g/L, the reference ranges of TT were 12.0-19.0 s and 11.5-18.4 s. Compared with early pregnancy, PT, APTT and TT shortened significantly, while the Fib significantly increased in late pregnancy (all P<0.001). PT, APTT and TT of advanced and non-advanced age pregnant women were significantly different (all P<0.01). Compared with the ranges of non-pregnant population, more pregnant women were included in the normal pregnant reference ranges of PT in early pregnancy and APTT in the early and late pregnancy, while the incidence of pregnancy complications had no significant differences (all P>0.05). The incidence of fetal distress was higher and the incidence of preterm birth was lower in the reference range of PT in late pregnancy. The incidence of gestational diabetes mellitus was higher in the early and late gestational Fib reference ranges, and the incidence of hypertensive disorders in pregnancy was higher in the late gestational Fib reference range (all P<0.05). Conclusions:The coagulation function of pregnant women increases significantly with the growth of pregnancy, and there is a significant difference between advanced significantly and non-advanced age pregnant women. The recommended ranges of normal pregnant women′s early and late pregnancy PT are 10.0-13.9 s and 9.6-12.3 s, the recommended ranges of APTT are 22.6-35.3 s and 22.4-30.9 s, the recommended ranges of TT are 12.0-19.0 s and 11.5-18.4 s. The appropriate ranges of normal pregnant women′s early and late pregnancy Fib still need further exploration.

Objective:To explore the difference of high-risk factors between early-onset and late-onset pre-eclampsia, and to further understand high-risk factors of pre-eclampsia.Methods:Clinical data of pre-eclampsia pregnant women in 160 medical institutions in China in 2018 were retrospectively analyzed, including 8 031 cases of early-onset pre-eclampsia and 12 969 cases of late-onset pre-eclampsia. The proportion of high-risk factors, different body mass index (BMI) and age stratification between early-onset group and late-onset group were compared.Results:(1) Univariate analysis of high-risk factors: the proportions of high-risk factors in early-onset group and late-onset group were compared, and the differences were statistically significant (all P<0.05). Among them, the proportions of primipara and multiple pregnancy in early-onset group were lower than those in late-onset group, while the proportions of pregnant women with advanced age, irregular antenatal examination, obesity, family history of hypertension, pre-eclampsia, diabetes, kidney diseases, immune system diseases and assisted reproductive technology were higher than those in late-onset group. (2) Hierarchical analysis of BMI: the proportion of pregnant women with BMI≥24 kg/m 2 in early-onset group [48.2% (2 828/5 872) vs 45.5% (4 177/9 181), respectively; P=0.001] and the proportion of pregnant women with BMI ≥28 kg/m 2 in early-onset group [19.5% (1 143/5 872) vs 18.0% (1 656/9 181), respectively; P=0.028] were significantly higher than those in late-onset group. (3) Age stratification analysis: the proportion of pregnant women aged 35-39 years in the early-onset group [21.8% (1 748/8 023) vs 17.5% (2 110/12 068), respectively; P<0.01], the proportion of pregnant women 40-44 years old [6.8% (544/8 023) vs 5.4% (648/12 068), respectively; P<0.01], and the proportion of pregnant women ≥45 years old [0.7% (58/8 023) vs 0.5% (57/12 068), respectively; P=0.021] were significantly higher than those in the late-onset group. (4) Multivariate analysis: advanced age (≥35 years old), multiple pregnancy, irregular antenatal examination or transfer from other hospitals, family history of hypertension (including paternal, maternal and parental lines), previous history of pre-eclampsia, kidney diseases, immune system diseases (systemic lupus erythematosus, antiphospholipid antibody syndrome) and assisted reproductive technology pregnancy were the risk factors affecting the severity of pre-eclampsia (all P<0.05). Conclusion:Pregnant women with high risk factors such as age ≥35 years old, BMI ≥24 kg/m 2 before pregnancy, family history of hypertension, history of pre-eclampsia, chronic kidney diseases, immune diseases (mainly including systemic lupus erythematosus and antiphospholipid syndrome) and assisted reproductive technology are more likely to have early-onset pre-eclampsia.

Objective To evaluate the risk factors and sonographic findings of pregnancies complicated by placenta increta or placenta percreta. Methods Totally, 2219 cases were retrospectively analyzed from 20 tertiary hospitals in China from January 2011 to December 2015. The data were collected based on the original case records. All cases were divided into two groups, the placenta increta (PI) group (79.1％, 1755/2219) and the placenta percreta (PP) group (20.9％, 464/2219), according to the degree of placental implantation. The risk factors and sonographic findings of placenta increta or percreta were analyzed by uni-factor and logistic regression statistic methods. Results The risk factors associated with the degree of placental implantation were age, gravida, previous abortion or miscarriage, previous cesarean sections, and placenta previa (all P<0.05), especially, previous cesarean sections (χ2=157.961) and placenta previa (χ2=91.759). Sonographic findings could be used to predict the degree of placental invasion especially the boundaries between placenta and uterine serosa, the boundary between placenta and myometrium, the disruption of the placental-uterine wall interface and loss of the normal retroplacental hypoechoic zone(all P<0.01). Conclusions Previous cesarean sections and placenta previa are the main independent risk factors associated with the degree of placenta implantation. Ultrasound could be used to make a prenatal suggestive diagnosis of placenta accreta spectrum disorders.

To investigate the clinical efficacy of sorafenib in the treatment of primary hepatic carcinoma (PHC) and its effects on serum vascular endothelial growth factor receptor -2 (VEGFR -2) and placental growth factor (PLGF) levels.Methods A total of 110 patients with a confirmed diagnosis of PHC who received treatment in Jinshan Hospital Affiliated to Fudan University from July 2014 to March 2016 were randomly and equally divided into observation group and control group .The control group was given routine treatment, while the observation group received sorafenib in addition to the routine treatment .Serum levels of VEGFR -2 and PLGF were measured by ELISA.Liver function parameters, aspartate aminotransferase (AST), prothrombin time (PT), total bilirubin (TBil), albumin (Alb), and alanine aminotransferase (ALT), were also recorded.Comparison of continuous data between groups was made by independent samples t -test, and the changes in continuous data after intervention in each group were evaluated by paired samples t -test.Comparison of categorical data between groups was made by chi -square test.Results The observation group showed significant reductions in serum VEGFR -2 and PLGF levels after treatment (VEGFR -2: 7053.2 ±1836.1 ng/L vs 8721.4 ±2427.8 ng/L, t =4.089, P <0.001; PLGF: 468.4 ±136.5 pg/ ml vs 656.8 ±191.4 pg/ml, t =5.975, P <0.001).After treatment, the observation group had significantly lower serum VEGFR -2 and PLGF levels than the control group (VEGFR -2: 7053.2 ±1836.1 ng/L vs 8097.5 ±2325.4 ng/L, t =2.64, P <0.05; PLGF: 468.4 ± 136.5 pg/ml vs 643.3 ±195.8 pg/ml, t =2.48, P <0.05).The observation group showed significant changes in serum AST and ALT lev - els after treatment (t =4.302 and 3.097, both P <0.05).After treatment, the observation group had significantly lower serum AST and ALT levels than the control group (t =2.56 and 2.39, both P <0.05).Compared with the control group, the observation group had better follow -up results, with a significantly increased disease control rate (27.3% vs 47.3% , χ2 =4.705, P =0.030), and had a significantly higher survival rate at 40 months after treatment (43.6% vs 69.1%, χ2 =7.245, P =0.007).Conclusion Sorafenib is effective in the treatment of PHC patients, as it can significantly reduce the serum levels of VEGFR -2 and PLGF, prolong the survival time of patients, and improve the prognosis of patients.

Objective To study the changes in cesarean delivery rate (CSR) and indications against the background of two-child policy. Methods Maternal information and indications for cesarean delivery were retrospectively obtained from medical records of 62007 women who delivered at the Obstetrics and Gynecology Hospital of Fudan University between January 2013 and December 2016. Indications for cesarean section were divided into 16 categories, such as maternal or fetal indication, repeat cesarean section, maternal request, labor arrest disorders, fetal distress, and so on. Changes in CSR and the proportion of cesarean delivery for each indication were evaluated. One-way analysis of variance, Chi-square or Fisher's exact test were used for statistical analysis. The average annual percent change (AAPC) in cesarean delivery rate was calculated by Joinpoint Analyses software. Relative contribution of each indication to the overall increase or decrease in CSR was analyzed using the data of the years of 2013 and 2016. Results The CSR dropped from 45.2％ (6683/14798) in 2013 to 38.3％ (6546/17104) in 2016. The rate of cesarean delivery due to maternal request and labor arrest disorders decreased significantly (χ2=49.402 and 14.617, both P<0.05) .The rate of cesarean delivery due to labor arrest disorders in all cases decreased sharply from 14.7‰ in 2013 to 0.9‰ in 2016 at an annual decrease of 48.0％ (95％CI: - 67.6％- - 21.5％). It was also worth noting that the rate of cesarean delivery on maternal request in all cases decreased from 119.3 ‰ in 2013 to 40.7 ‰ in 2016 at an average annual decrease of 30.1％ (95％CI: - 31.3％- - 28.9％). Despite of a limited number of cesarean delivery cases for uterine scar caused by leiomyoma resection, its rate increased from 1.4 per 1000 deliveries in 2013 to 2.9 per 1000 deliveries in 2016 with the highest average annual increase of 32.3％ (95％CI: 10.1％-60.9％), followed by the rate of cesarean delivery due to maternal pyrexia, increasing from 6.6 per 1000 deliveries in 2013 to 16.4 per 1000 deliveries in 2016 at an average annual increase of 27.4％ (95％CI: 11.0％-46.5％), and the rate of cesarean delivery due to repeat cesarean section, increasing from 67.6 per 1000 deliveries in 2013 to 113.9 per 1000 deliveries in 2016 at an average annual increase of 19.0％ (95％CI: 5.0％-34.6％). The first two positive contributors to the total decrease of CSR were maternal request and labor arrest disorders (144.2％ and 27.7％, respectively), while the first two negative contributors were repeat cesarean section and maternal pyrexia (-102.3％ and -18.9％, respectively). Conclusions The CSR is reduced after the implementation of two-child policy through active control on maternal request and application of new partogram.

Objective To summarize the experience of multidisciplinary consultation for prenatal fetal deformity, and to explore the mode suitable for China. Methods The Obstetrics and Gynecology Hospital of Fudan University and Children's Hospital of Fudan University established a joint multidisciplinary consultation center, including obstetrics, pediatrics, pediatric surgery, ultrasound and other departments. A total of 3 378 pregnant women visited the consultation center from July 31, 2003 to August 1, 2013. After consultation, treatment was divided into three classes:pregnancy termination, pregnancy continuation and perinatal treatment. Follow-up was made through correspondence and telephone communication. Retrospective analysis on reasons for consultation, fetal structural abnormalities of the classification system, chronological order of abnormalities, gestational weeks of diagnosis, maternal-related factors, treatment and prognosis was performed. Results (1) Reasons for consultation:Among 3 378 women undertaking prenatal multidisciplinary consultation, 3 243 (96.00%) were due to fetal factors, and 135 (4.00%) were due to maternal factors. (2) Classification of fetal structural abnormalities:Among the 3 243 cases undertaking consultation with fetal factors, fetal abnormality was found in 80.85%(2 622/3 243). The most common were neurological abnormalities(23.19%, 608/2 622), followed by urinary tract malformation (20.25%, 531/2 622) and cardiovascular malformation (15.48%, 406/2 622). These were followed by digestive system malformation, limb deformities and space-occupying lesions. There were 156 cases of multiple malformations. (3) Average gestational weeks for diagnosis of fetal deformity:The 2 622 cases of fetal deformity were diagnosed at a mean (26.7± 2.1) of gestational weeks (21.1–30.4 weeks). Urinary tract malformations were detected at (24.0±0.7) weeks, whereas digestive system malformations were detected at (28.3±2.6) weeks. (4) Induced labor:Induced labor cases accounted for 35.66% (935/2 622), among which, 92 cases were fetal intrauterine death and 843 cases were active choice. The several highest induced labor rates resulted from multiple malformations (75.64%, 118/156), abdominal wall defects (62.22%, 28/45), diaphragmatic hernia (61.54%, 24/39), cleft lip and palate (55.32%, 26/47) and cardiovascular malformations (49.51%, 201/406). For nervous system (27.80%, 169/608), urinary tract (25.80%, 137/531) and digestive system malformations (26.94%, 66/245), induced labor rates were <30%. For abdominal lesions (14.04%, 25/178) and sacrococcygeal teratoma (13.64%, 3/22), induced labor rates were<15%. (5) Continuation of pregnancy in 1 687 cases:Cesarean section was conducted in 1 046(61.94%). Neonatal death occurred in 117(6.94%).(6) Perinatal treatment:Twenty-one cases were treated during pregnancy, including thirteen cases with fetal ascites and hydrothorax treated by drainage, five cases with fetal anemia treated by intrauterine transfusion and three cases with fetal tachycardia treated by digoxin. Ten cases were treated by ex-utero intrapartum treatment. After birth, 297 newborns immediately underwent neonatal surgery. Among these, 259 cases underwent radical surgery, eleven palliative surgery, and sixteen elective surgery after follow-up. Conclusions Prenatal multidisciplinary consultation can make comprehensive multidisciplinary assessment of fetal prognosis and improve the diagnosis and treatment of structural malformations.

Objective To establish a stable animal model for sequentially dynamic and direct monitoring of the skin wound infection. Methods The mice with full-thickness skin incisions were replicated. After immediate subcutaneous suture,the mice were randomly divided into four groups,ie,Group A was inoculated with 50 μl sterile PBS solution),Groups B,C and D were inoculated with 50 μl suspension containing 1 × 106,1 × 108 and 1 × 1010 colony forming unit (CFU)/ml bioluminescent methicillin-resistant staphylococcus aureus (MRSA) respectively.Then,the diet behavior of each group was observed and the mean weight and mortality of each group were also recorded at different time points.The bioluminescent intensity of fluoresce in the wounds was recorded at different time points by using the charge-coupled device (CCD) based imaging system.Local wound tissues were incised at 24 hours after inoculation for HE staining so as to observe wound inflammatory reaction in each group.Wound healing time of each group was also recorded. Results ( 1 ) Average weight:Groups A and B showed unobvious changes in weight; Group C lightened until day 3 after inoculation and then recovered gradually to the preinoculation level at day 14; Group D lightened gradually until death.(2)Mortality:Groups A and B had no death; Group C had 10％ deaths at day 14; Group D had 100％ deaths.(3) Bioluminescent intensity of wounds:Groups A and B showed a gradual weakened luminescence since the day of inoculation and had almost complete disappearance at days 5 and 7 respectively; there was no sign of obvious increase or decrease in Group C from the day of inoculation till day 14 ; Group D had a gradual increase since the day of inoculation and the luminous area expanded until the death.(4) HE staining at 24 hours after inoculation:all the four groups showed inflammatory cell infiltration,especially in Groups C and D.(5) Wound healing time:wound healed at days 5 and 7 after inoculation in Groups A and B; the wounds showed no healing even at day 14 in the Group C,but the wounds length and area did not show obvious enlargement or diminishment ; the wounds extended gradually until the death in the Group D,since the day of inoculation. Conclusions The inoculation of 50 μl suspension with 1 × 108 CFU/ml bioluminescent MRSA to full-thickness skin incision rats allows direct,real-time dynamic and continuous detection of the occurrence and development of the wound infections.The infection model is easy to make and has stability and high repeatability.

ObjectiveTo develop a new sutureless technique (photochemical tissue bonding,PTB ) for repair of corneal perforation. Methods A total of 60 rabbits were used for creating corneal perforation models.The corneal perforation on the left eye was repaired by sutures and the injury on the right eye was fixed with the use of amniotic membrane with PTB.The outcomes of the two mentioned repair methods were compared by observing the leakage of aqueous and the morphology of the anterior chamber at different instants,measuring the intraocular pressure (IOP) and observing the formation of neo-vessels and scars of cornea in the use of histological analysis. Results There was no leakage of aqueous and no difference for morphology evaluation in both treatments.PTB could adhere AM on the cornea to restore the corneal perforation.The peak IOP in the PTB treatment group at days 0,7 and 14 postoperative [ (531.2 ±49.5) mm Hg,(542.6 ±74.8) mm Hg and (603.9 ±69.1) mm Hg,respectively] was significantly higher than that in the suture group at the same instants [ (41.3 ±12.7) mm Hg,(142.6 ±25.4) mm Hg and (333.3 ± 66.7) mm Hg,respectively] (P ＜0.O1 ).Compared with suture repair,the treatment with PTB resulted in a better outcome of wound healing with less neo-vessels and less scars of cornea. Conclusion PTB treatment for repair of corneal perforation is superior to suture repair.

Objective To investigate the role of human leukocyte antigen-G ( HLA-G ) on the invasion and the molecular mechanism involved in this cellular progress in HTR-8/SVneo cell line. Methods There were three groups: groups of transfection, negative control and blank control, which corresponding to treatment by HLA-G specific siRNA, negative siRNA and only lipofectamine 2000 using lipofection technology in HTR-8/SVneo cell line. The efficiency of down-regulated of HLA-G was detected by reverse transcription-polymerase chain reaction and western blot analysis in mRNA and protein level,respectively. Changes of p38 mitogen-activated protein kinases (p-p38MAPK)/p38MAPK protein levels and the cell invasion were respectively detected by western blot analysis and transwell test. Results ( 1 ) The mRNA levels of HLA-G transfection group, negative control group and blank control group were 0. 26 ±0. 08, 0. 71 ±0. 11, 0. 79 ±0. 07, respectively. There was significant difference between transfection group and negative control group ( P ＜ 0. 01 ), while there was no significant difference between negative control group and blank control group ( P ＞ 0. 05 ). The efficiencies of down-regulated of HLA-G were ( 69. 8 ±6. 3)%, ( 14. 9 ± 2. 2 )%, 0 in transfection group, negative control group and blank control group respectively in mRNA level. (2)In protein levels, HLA-G were 0. 20 ±0. 15, 0. 75 ±0. 12, 0. 76 ±0. 21 in transfection group, negative control group and blank control group, respectively. There was significant difference between transfection group and negative control group ( P ＜ 0. 01 ), whereas there was no significant difference between negative control group and blank control group ( P ＞ 0. 05 ). The efficiencies of down-regulated of HLA-G were (81. 1 ± 14.4)%, ( 18.0 ± 7.7)%, 0 in transfection group, negative control group and blank control group respectively. ( 3 ) The invasive number of transfection group, negative control group and blank control group were 57 ± 38,364 ± 79 and 260 ± 84, respectively, with a significant difference between transfection group and negative control group (P ＜ 0. 01 ). There was no significant difference between negative control group and blank control group ( P ＞ 0. 05 ). ( 4 ) The p-p38MAPK/p38MAPK values of the HLA-G transfection group, negative control group and blank control group were 0. 74 ±0.04, 0. 47 ± 0. 09 and 0. 36 ± 0. 21, respectively. HLA-G transfection group was significantly different compared with the other two groups( P ＜0. 01 ). (5)Without or with SB203580, the p-p38MAPK/ p38MAPK values of the HLA-G transfection group were 0. 89 ± 0. 09 and 0. 16 ± 0. 04, the values of negative control group and blank control group were 0.76 ±0.08, 0. 14 ±0.03 and 0.51 ±0.05, 0.03 ±0.01, respectively. There was significant difference between without SB203580 and with SB203580 ( P ＜ 0. 01 ). (6)Without or with SB203580, the invasive number of transfection group were 51 ± 13 and 90 ± 21 ,respectively,which was significantly different ( P ＜ 0. 01 ). The invasive number of negative control group and blank control group were 290 ± 52, 298 ± 33 and 290 ± 73, 264 ± 64, respeczively, which was no significant difference between without SB203580 and with SB203580 (P ＞ 0. 05 ). Conclusions HLA-G gene may regulate invasion of trophoblast-derived cell line HTR-8/SVneo via p38MAPK signaling pathway. The lower expression of HLA-G in trophoblast cells may lead to the occurrence of pathologic pregnancy.

ObjectiveTo observe production of vascular endothelial growth factor (VEGF) induced by granulocyte/macrophage colony-stimulating factor (GMCSF)via ERK nerve growth factor (NF)-κB singling pathway in human fibroblasts during wound healing and explore relating mechanism.MethodsHuman fibroblasts from the injured skin were used for this study and treated with GMCSF.RT-PCR was used for analyzing the protein and mRNA levels of VEGF and Western blotting was employed to determine the phosphorylation of ERK. The fibroblasts were pre-treated with ERK specific inhibitor PD98059 and further treated with GMCSF, then the fibroblasts and the supernatant were collected for detection of protein level of VEGF by means of Western blot. ERK signal pathway was inhibited to detect the activation of NF-κB by means of immunofluorescence staining. Furthermore, the nuclear and cytoplasmic extraction kit was used to separate the cytoplasm and nucleus and Western blot employed for observation of the NF-κB activation. ResultsThe mRNA level and protein level of VEGF were increased significantly with treatment with higher concentration of GMCSF in a dose-dependent manner. VEGF mRNA level was increased two hours after administration with GMCSF and reached peak at 4-6 hours. GMCSF could remarkably activate the ERK phosphorylation. Compared with GMCSF, the ERK specific inhibitor PD98059inhibited significantly the effect of GMCSF in inducing VEGF expression (P ＜ 0.05). Western blot and immunofluorescence staining analyses showed that the activation of NF-ΚB was inhibited with reduced production of VEGF after GMCSF treatment.Conclusion GMCSF up-regulates production of VEGF through activating NF-κB via ERK signal pathway in the human fibroblasts.