Downregulation of CDC42 inhibits the proliferation and stemness of human trophoblast stem cell via EZRIN/YAP inactivation.

Placental dysplasia increases the risk of recurrent spontaneous abortion (RSA). However, the underlying mechanism regulating placental development remains unclear. In this study, we showed that the expression of CDC42 was decreased in the villous tissue of RSA samples compared to healthy controls. Further examination demonstrated that CDC42 deficiency led to the differentiation of human trophoblast stem cells (hTSCs) and inhibited their proliferation. Genetic manipulation of YAP and EZRIN in hTSCs revealed that CDC42 regulates the stemness and proliferation of hTSCs; this is dependent on EZRIN, which translocates YAP into the nucleus. Moreover, the expression pattern of EZRIN, YAP, and Ki67 was also abnormal in the villous tissue of RSA samples, consistent with in vitro experiments. In summary, these findings suggest that the CDC42/EZRIN/YAP pathway plays an important role in placental development.

Dexmedetomidine reduced cytokine release during postpartum bleeding-induced multiple organ dysfunction syndrome in rats.

Dexmedetomidine (DEX) is an α 2-adrenergic agonist. It decreases the levels of norepinephrine release, resulting in a reduction of postsynaptic adrenergic activity. In the present study, the effects of DEX on postpartum bleeding-induced multiple organ dysfunction syndrome (BMODS) were studied in rats in which BMODS was induced by the combination of hypotension and clamping of the superior mesenteric artery. We evaluated the role of dexmedetomidine (DEX) in cytokine release during postpartum BMODS in rats. In summary, the present study demonstrated that DEX administration reduced IFN-r and IL-4 release and decreased lung injury during postpartum BMODS. It is possible that DEX administration decreased inflammatory cytokine production in BMODS by inhibiting inflammation and free radical release by leukocytes independent of the DEX dose.

Geographic variation in management of patients with placenta accreta spectrum: An international survey of experts (GPASS).

OBJECTIVE: To describe global geographic variations in the diagnosis and management of placenta accreta spectrum (PAS). METHODS: An international cross-sectional study was conducted among PAS experts practicing at medical institutions in member states of the United Nations. Survey questions focused on diagnostic evaluation and management strategies for PAS. RESULTS: A total of 134 centers participated. Participating centers represented each of the United Nations' designated regions. Of those, 118 (88%) reported practicing in a medium-volume or high-volume center. First-trimester PAS screen was reported in 35 (26.1%) centers. Respondents consistently implement guideline-supported care practices, including utilization of ultrasound as the primary diagnostic modality (134, 100%) and implementation of multidisciplinary care teams (115, 85.8%). Less than 10% of respondents reported routinely managing PAS without hysterectomy; these centers were predominantly located in Europe and Africa. Antepartum management and availability of mental health support for PAS patients varied widely. CONCLUSION: Worldwide, there is a strong adherence to PAS care guidelines; however, regional variations do exist. Comparing variations in care to outcomes will provide insight into the clinically significant practice variability.

The Risk of Postpartum Hemorrhage Following Prior Prelabor Cesarean Delivery Stratified by Abnormal Placentation: A Multicenter Historical Cohort Study.

Background: Prior prelabor cesarean delivery (CD) was associated with an increase in the risk of placenta previa (PP) in a second delivery, whether it may impact postpartum hemorrhage (PPH) independent of abnormal placentation. This study aimed to assess the risk of PPH stratified by abnormal placentation following a first CD before the onset of labor (prelabor) or intrapartum CD. Methods: This multicenter, historical cohort study involved singleton, pregnant women at 28 weeks of gestation or greater with a CD history between January 2017 and December 2017 in 11 public tertiary hospitals within 7 provinces of China. PPH was analyzed in the subsequent pregnancy between women with prior prelabor CD and women with intrapartum CD. Furthermore, PPH was analyzed in pregnant women stratified by complications with PP alone [without placenta accreta spectrum (PAS) disorders], complications with PP and PAS, complications with PAS alone (without PP), and normal placentation. We performed multivariate logistic regression to calculate adjusted odds ratios (aOR) and 95% CI controlling for predefined covariates. Results: Out of 10,833 pregnant women, 1,197 (11%) women had a history of intrapartum CD and 9,636 (89%) women had a history of prelabor CD. Prior prelabor CD increased the risk of PP (aOR 1.91, 95% CI 1.40-2.60), PAS (aOR 1.68, 95% CI 1.11-2.24), and PPH (aOR 1.33, 95% CI 1.02-1.75) in a subsequent pregnancy. After stratification by complications with PP alone, PP and PAS, PAS alone, and normal placentation, prior prelabor CD only increased the risk of PPH (aOR 3.34, 95% CI 1.35-8.23) in a subsequent pregnancy complicated with PP and PAS. Conclusion: Compared to intrapartum CD, prior prelabor CD increased the risk of PPH in a subsequent pregnancy only when complicated by PP and PAS.

Effect of blood pressure on reversible posterior leukoencephalopathy syndrome in pre-eclampsia or eclampsia.

Reversible posterior leukoencephalopathy syndrome (RPLS) is a critical maternal complication in some pre-eclampsia (PE) and nearly all eclampsia patients; RPLS is associated with high blood pressure (BP). However, the effect of BP on RPLS and the different characteristics of RPLS in PE or eclampsia are largely unknown. We consecutively collected data from 69 patients who were diagnosed with RPLS in PE or eclampsia between 2013 and 2017. The BP and biochemical indicators at onset and post onset of RPLS were examined to explore their likely correlation with RPLS. We grouped patients into PE (n=40) and eclampsia (n=29) groups according to whether a seizure had occurred. Information regarding BP, clinical symptoms and imaging features was collected retrospectively to explore the differences between groups. BP measurements (moderate and severe hypertension, systolic pressure (SBP), diastolic pressure (DBP) and mean arterial pressure (MAP) levels) and biochemical indicators (uric acid, lactate dehydrogenase (LDH), C-reactive protein and WBC) were higher at the onset of RPLS than post-onset of RPLS (P<0.001), whereas normal BP and serum albumin levels were lower (P<0.001). Moreover, the BP values (SBP, DBP and MAP) and LDH levels were significantly correlated with the degree of edema (Spearman's correlation, P<0.01). These results suggest that hypertension and LDH are likely factors in the development of RPLS in PE or eclampsia. Moreover, BP and LDH were closely related to the degree of brain edema, However, no significant differences were found between the PE and eclampsia groups with the exception of age and consciousness impairment.

Outcomes of the second pregnancy after Triple-P procedure in women complicated with placenta accreta spectrum disorders / 中华妇产科杂志

Objective:To investigate the safety of the Triple-P procedure in women complicated with severe placenta accreta spectrum disorders (PAS) and its influence on second pregnancy.Methods:From January 2015 to December 2017, the outcomes of the second pregnancy after the Triple-P procedure in 11 pregnant women complicated with PAS in the Third Affiliated Hospital of Guangzhou Medical University and the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed.Results:By December 2021, a total of 11 pregnant women who underwent the Triple-P procedure for PAS had a second pregnancy, with a median interval of 3 years (2-3 years). Of the 11 pregnant women, 7 delivered after 36 weeks of gestation. The median gestational age was 38 weeks, and 4 terminated within the first trimester. PAS recurred in 1 of 7 pregnant women (1/7) and was associated with placenta previa. All of the 7 pregnant women were delivered by cesarean section, with a median postpartum blood loss of 300 ml (200-450 ml), and only one pregnant woman required blood transfusion. None of the pregnant women were transferred to the intensive care unit, and there were no uterine rupture, bladder injury, puerperal infection, and neonatal adverse outcomes.Conclusion:Pregnant women who underwent the Triple-P procedure for severe PAS could be considered for second pregnancy with strictly management by an experienced multidisciplinary team, which may result in a good outcome.

Effects of placenta previa on surgical and pregnancy outcomes in patients with total/subtotal or segmental hysterectomy attributed to placenta accreta spectrum disorders / 中华围产医学杂志

Objective:To investigate the effects of placenta previa on the surgical and pregnancy outcomes in patients with total/subtotal or segmental hysterectomy attributed to placenta accreta spectrum disorders (PAS).Methods:This study retrospectively enrolled 510 patients who gave birth and underwent total/subtotal hysterectomy or segmental hysterectomy (local implantation site) due to PAS at the third Affiliated Hospital of Guangzhou Medical University from January 1, 2017, to December 31, 2022. These subjects were divided into the placenta previa group (427 cases) and non-placenta previa group (83 cases). According to the type of hysterectomy, they were further divided into the total/subtotal hysterectomy and placenta previa subgroup (221 cases), total/subtotal hysterectomy and non-placenta previa subgroup (23 cases), segmental hysterectomy and placenta previa subgroup (206 cases), and segmental hysterectomy and non-placenta previa subgroup (60 cases). Nonparametric test or Chi-square test were used to compare the differences in the clinical features, surgical and pregnancy outcomes between different groups. Binary logistic regression was used to analyze the effects of placenta previa on the risk of additional surgical procedures and adverse maternal outcomes. Results:(1) Compared with the non-placenta previa group, the hemorrhage volume within 24 h postpartum [1 541 ml (1 036-2 368 ml) vs 1 111 ml (695-2 000 ml), Z=－3.91] and the proportion of women requiring additional surgical procedures [84.8% (362/427) vs 69.9% (58/83), χ2=10.61], with total/subtotal hysterectomy [51.8% (221/427) vs 27.7% (23/83), χ2=16.10], cystoscopy and/or ureteral stenting [60.7% (259/427) vs 31.3% (26/83), χ2=24.25], total adverse pregnancy outcomes [86.9% (371/427) vs 65.1% (54/83), χ2=17.75], hemorrhage volume>1 500 ml within 24 h postpartum [54.1% (231/427) vs 33.7% (28/83), χ2=29.94], transfusion of blood products [75.9% (324/427) vs 47.0% (39/83), χ2=28.27] were all higher in the placenta previa group (all P<0.05). Binary logistic regression analysis found that for PAS patients with hysterectomy, regardless of the hysterectomy type (total/subtotal/segmental), placenta previa was risk factor for requiring additional surgical procedures ( aOR=3.26, 95% CI: 1.85-5.72) and adverse pregnancy outcomes ( aOR=5.59, 95% CI: 2.01-6.42), even if adjusting for the confounding factors such as maternal age, number of previous cesarean sections, parity, gestational weight gain, twin pregnancy, and the use of assisted reproductive technology. (2) In patients with total/subtotal hysterectomy, the proportion of women requiring additional surgical procedures was higher in those with placenta previa [82.8% (183/221) vs 56.5% (13/23), χ2=9.11] than those without placenta previa, especially the proportion of cystoscopy and/or ureteral stenting [67.9% (150/221) vs 34.8% (8/23), χ2=9.99] (both P<0.05). However, no significant difference was found in adverse pregnancy outcomes [89.6% (198/221) vs 87.0% (20/23), χ2<0.01, P=0.972] between the two groups. In patients with segmental hysterectomy, higher proportions of women requiring additional surgery [86.9% (179/206) vs 75.0% (45/60), χ2=4.94], with adverse pregnancy outcomes [84.0% (173/206) vs 56.7% (34/60), χ2=25.31], cystoscopy and/or ureteral stenting [52.9% (109/206) vs 30.0% (18/60), χ2=9.78], vascular occlusion [94.2% (194/206) vs 71.7% (43/60), χ2=24.23], hemorrhage volume>1 500 ml within 24 h postpartum [46.6% (96/206) vs 23.3% (14/60), χ2=10.37], and transfusion of blood products [68.9% (142/206) vs 33.3% (20/60), χ2=24.73] were found in the placenta previa group (all P<0.05). Furthermore, patients with placenta previa had more hemorrhage volume within 24 h postpartum [1 368 ml (970-2 026 ml) vs 995 ml (654-1 352 ml), Z=－3.66, P<0.001] in the segmental hysterectomy subgroup. After adjusting for the confounding factors such as age, number of previous cesarean sections, parity, gestational weight gain, twin pregnancy, and the use of assisted reproductive technology, binary logistic regression analysis found that placenta previa did not increase the risk of additional surgical operations ( aOR=2.71, 95% CI: 0.99-7.42) and adverse pregnancy outcomes ( aOR=2.14, 95% CI: 0.54-8.42) in patients with total/subtotal hysterectomy but were risk factors of the two outcomes for those with segmental hysterectomy ( aOR=4.67, 95% CI: 2.15-10.10; aOR=3.80, 95% CI: 1.86-7.77). Conclusions:Placenta previa increases the risk of additional surgical procedures and adverse pregnancy outcomes in patients with total/subtotal or segmental hysterectomy caused by PAS. Appropriate preparation is required after the clinical diagnosis of PAS with placenta previa.

Recommendations for the diagnosis and treatment of maternal SARS-CoV-2 infection / 中华围产医学杂志

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread worldwide and threatened human's health. With the passing of time, the epidemiology of coronavirus disease 2019 evolves and the knowledge of SARS-CoV-2 infection accumu-lates. To further improve the scientific and standardized diagnosis and treatment of maternal SARS-CoV-2 infection in China, the Chinese Society of Perinatal Medicine of Chinese Medical Association commissioned leading experts to develop the Recommendations for the Diagnosis and Treatment of Maternal SARS-CoV-2 Infection under the guidance of the Maternal and Child Health Department of the National Health Commission. This recommendations includes the epidemiology, diagnosis, management, maternal care, medication treatment, care of birth and newborns, and psychological support associated with maternal SARS-CoV-2 infection. It is hoped that the recommendations will effectively help the clinical management of maternal SARS-CoV-2 infection.

Analysis of the efficacy and related influencing factors of pelvic packing in the treatment of intractable postpartum hemorrhage after emergency perinatal hysterectomy / 中华妇产科杂志

Objective:To investigate the effect of pelvic packing on the control of intractable postpartum hemorrhage after emergency perinatal hysterectomy (EPH).Methods:Eleven cases with complete clinical data of pelvic packing due to failure of hemostasis after EPH were collected to evaluate the outcome, complications, hospital stay of pregnant women, and to analyze the factors affecting the effect of pelvic packing. The cases included patients who were admitted to the Third Affiliated Hospital of Guangzhou Medical University after pelvic packing treatment in the other hospital due to continuous bleeding after EPH or who were referred to our hospital for pelvic packing treatment due to continuous bleeding after EPH from January 2014 to August 2021.Results:The median gestational week of 11 pregnant women was 38.3 weeks(38.0-39.9 weeks) , and the methods of termination of pregnancy were cesarean section in 7 cases (7/11) and vaginal delivery in 4 cases (4/11). The median time between postpartum hemorrhage and pelvic tamponade was 10 hours (5-57 hours), the median amount of bleeding was 8 500 ml(4 800-15 600 ml) , the median number of pelvic tamponade was 3 pieces (2-7 pieces), and the median retention time of gauze pad was 6.0 days (3.0-6.0 days). The median frequency of laparotomy in this pregnancy was 3 times (2-3 times), with a maximum of 4 among the 11 cases, the first pelvic packing was successful in hemostasis in 9 cases, and the final successful treatment in all of the 11 cases. All parturients had hemorrhagic shock (11/11) and disseminated intravascular coagulation (11/11) before pelvic packing. Other common complications were multiple organ dysfunction syndrome (9/11), cardiac arrest (4/11), deep vein thrombosis (3/11), septic shock (3/11), and intestinal obstruction (1/11). All parturients took out the gauze after the coagulation function returned to normal and there was no active bleeding. The recovery time of coagulation function in 11 cases was 3 days (3-5 days), the retention time of gauze pad was 6 days (3-6 days), the median length of stay in intensive care unit was 14 days (11-26 days), and the median total length of stay was 22 days (16-49 days).Conclusions:Pelvic packing could be used as a temporary strategy for intractable postpartum hemorrhage after EPH, which provides a key time for injury control resuscitation for patients with unstable vital signs. This technology provides an opportunity for referral to superior medical institutions and further treatment.

Intra-abdominal aortic balloon occlusion in the management of placenta percreta / 中华医学杂志(英文版)

BACKGROUND@#Massive bleeding is the main concern for the management of placenta percreta (PP). Intra-abdominal aortic balloon occlusion (IABO) is one method for pelvic devascularization, but the efficacy of IABO is uncertain. This study aims to investigate the outcomes of IABO in PP patients.@*METHODS@#We retrospectively reviewed the clinical data of PP cases from six tertiary centers in China between January 2011 and December 2015. PP cases with/without the use of IABO were analyzed. Propensity score matching analysis was performed to reduce the effect of selection bias. Postpartum hemorrhage (PPH) and the rate of hysterectomy, as well as neonatal outcomes, were analyzed.@*RESULTS@#One hundred and thirty-two matched pairs of patients were included in the final analysis. Compared with the control group, maternal outcomes, including PPH (68.9% vs. 87.9%, χ2 = 13.984, P < 0.001), hysterectomy (8.3% vs. 65.2%, χ2 = 91.672, P < 0.001), and repeated surgery (1.5% vs. 12.1%, χ2 = 11.686, P = 0.001) were significantly reduced in the IABO group. For neonatal outcomes, Apgar scores at 1 minute (8.67 ± 1.79 vs. 8.53 ± 1.68, t = -0.638, P = 0.947) and 5 minutes (9.43 ± 1.55 vs. 9.53 ± 1.26, t = 0.566, P = 0.293) were not significantly different between the two groups.@*CONCLUSIONS@#IABO can significantly reduce blood loss, hysterectomies, and repeated surgeries. This procedure has not shown harmful effects on neonatal outcomes.

Current situation and challenges in management of extremely premature infants / 中华围产医学杂志

Extremely premature infants with <28 weeks of gestational age are at higher risk of various complications after birth and have higher mortality and disability rate due to the extremely immature organs. In recent years, with the rapid development of the perinatal medical system and related therapeutic technology, extremely preterm infants' short- and long-term prognosis has been significantly improved. Since the new century, with the rapid social and economic development, the number of treated extremely premature infants and its survival rate in China has also significantly increased. However, compared with the developed countries, the gap still exists. Here we outline the current situation of the management of extremely premature infants in China and abroad and the challenges we faced.

New progress in prevention of preeclampsia / 中国医师杂志

Preeclampsia is a common gestational disease, involves multisystem disorder and carries risks for both mother and baby. Low-dose aspirin is the most comprehensive among the prevention candidates. The 2019 ACOG recommends the use of low-dose aspirin after 12 weeks of gestation as prevention if the patient has one or more of high-risk factors. WHO recommends calcium supplementation as one of strategy for prevention of preeclampsia, especially for the pregnant women who are likely to be low serum calcium or low calcium intake. Other medicines, antioxidants or sodium restriction are lack of evidence even present controversy. This paper highlights the latest guidelines, research findings and other new advances in preeclampsia prevention.

Clinical investigation in the methods for complete placenta previa labor induction in the second trimester / 中华妇产科杂志

Objective:To investigate the appropriate method of labor induction in the second trimester for complete placenta previa patients.Methods:The labor induction outcomes of 85 cases with complete placenta previa in the second trimester were retrospectively analyzed. Twenty patients in group A were treated with cesarean section, 30 patients in group B were treated with ethacridine and mifepristone combined with uterine artery embolization (UAE), and 35 patients in group C were induced by using ethacridine and mifepristone. The clinical features and induction outcomes of three groups were compared.Results:The total duration of labor in group B [(28.7±30.1) hours] was significantly longer than that of group C [(24.3±21.9) hours; P<0.05]. The total amount of blood loss during induction and labor in group B [(302±271) ml] was significantly lower than those of group C [(393±523) ml] and group A [(626±487) ml; P<0.05]. The incidence of fever in group B (13%, 4/30) was significantly higher than those of group C (11%, 4/35) and group A (10%, 2/20; P<0.05). In group C, 13 patients (37%, 13/35) underwent emergency UAE, and 2 patients (6%, 2/35) underwent emergency cesarean section. As to average hemoglobin level and blood transfusion rate, there were no difference among the three groups (all P>0.05). Conclusion:Prophylactic UAE combined with drug induction in patients with complete placenta previa in the second trimester could significantly reduce the amount of bleeding during induction and reduce the risk of emergency procedures.

Early-onset preeclampsia with or without fetal growth restriction: an analysis of 591 cases / 中华围产医学杂志

Objective To investigate whether fetal growth restriction (FGR) could be used as an indicator for severe early-onset preeclampsia.Methods A retrospective analysis was conducted on 591 women with early-onset preeclampsia and their fetuses and newborns in Departments of Obstetrics and Gynecology,Affiliated Hangzhou First People's Hospital,Zhejiang University School of Medicine,and the Third Affiliated Hospital of Guangzhou Medical University from January 2011 to December 2017.These cases were divided into two groups according to whether they were complicated by FGR (n=206,FGR group) or not (n=385,non-FGR group).Clinical datas were analyzed by t test or Chi-square test.Results (1) There was no significant difference between the two groups in terms of average maternal age,the ratio of primipara,the proportion of women with hypertension history,abnormal blood glucose or who received regular antenatal examination,gestational age at onset and termination or cesarean section rate.No maternal death was reported.(2)The systolic blood pressure and the incidence of hemolysis,elevated liver enzyme,low platelet count (HELLP) syndrome in the FGR group were lower than those in the non-FGR group [(167.0±21.5) vs (174.0±21.8) mmHg,t=-3.729 (1 mmHg=0.133 kPa);6.8％ (14/206) vs 13.8％ (53/385),x2=6.486].Although the incidence of absent or reverse diastolic umbilical artery flow in the FGR group was significantly higher [24.3％ (50/206) vs 14.5％ (56/385),x2=8.625],and the amniotic fluid index and placental weight were lower than those in the non-FGR group [(77.82±29.78) vs (90.53±43.83) mm,t=-2.837;(302.83±80.01) vs (330.98±61.01) g,t=-2.823],the stillbirth rate was lower[2.4％ (5/206) vs 6.5％ (25/385),x2=4.605] (all P ＜ 0.05).(3) Platelet counts in the FGR group were higher than those in the non-FGR group [(189.96 ± 65.43) vs (173.77 ± 62.88)× 109/L,t=2.923],while serum creatinine and D-dimer were lower [(70.99±22.97) vs (78.98±50.87) μ mol/L,t=-2.109;(491.01 ±401.98) vs (635.67±386.21) μg/L,t=-2.276] (all P ＜ 0.05).There was no significant difference in 24-hour urine protein excretion between the two groups.Conclusions FGR should not be used as an indicator for severe early-onset preeclampsia.

Regulatory effect of CLEC2D-CD161 interaction on killing capacity of decidual natural killer cells / 中华围产医学杂志

Objective@#To investigate the regulatory effect of CLEC2D-CD161 interaction on killing capacity of decidual natural killer (dNK) cells during early pregnancy and its association with the incidence of recurrent spontaneous abortion (RSA).@*Methods@#Decidua tissues were collected from normal pregnancies (n=16) and RSA cases (n=6) at 6-10 gestational weeks in the Department of Obstetrics and Gynecology of Peking University Third Hospital from October 2018 to May 2019. (1) Expressions of CLEC2D and CD161 in decidua from early pregnancy were detected using immunofluorescence. (2) Primary dNK cells were isolated from decidua from early pregnancy. dNK cells pre-treated with CD161 antibody (blocking CD161, B-CD161) were co-cultured with JEG-3 cells which were knocked-down by CLEC2D small interfering RNA (siCLEC2D), followed by killing capacity assessment of dNK cells by cytotoxicity assay and determination of expressions of related molecules by quantitive real-time polymerase chain reaction. (3) Western blot and flow cytometry were used to detect the expression of CLEC2D and CD161 in decidua tissues. Cytotoxicity assay was performed to analyze the killing capacity of dNK cells. T test was used for statistical analysis between normal and RSA cases.@*Results@#(1) CLEC2D was mainly expressed in extravillous trophoblast (EVT) cells and CD161 was mainly detected in dNK cells. CD161-positive dNK cells and CLEC2D-positive EVT cells were adjacently located in decidua tissues allowing their interaction. (2) Cytotoxicity assay suggested that CD161 blocking in dNK cells or CLEC2D knockdown in JEG-3 cells could enhance the cytotoxicity of dNK cells. The target cell lysis rates at the effector-target ratios of 40∶1, 20∶1, 10∶1 and 5∶1 in B-CD161 group were (59.12±4.56)%, (25.96±5.44)%, (13.60±8.94)% and (12.53±8.94)%, and in IgG control group were (20.01±1.96)%, (8.51±1.32)%, (3.24±0.75)% and (3.82±1.92)%, respectively. There were significant differences between the two groups at the effector-target ratios of 40∶1 (t=13.922, P<0.01) and 20∶1 (t=5.403 P<0.05), but not at 10∶1 or 5∶1 (P>0.05). The target cell lysis rates at the effector-target ratios of 40∶1, 20∶1, 10∶1 and 5∶1 in si-CLEC2D group were (43.37±2.01)%, (32.99±2.08)%, (23.47±1.36)% and (11.48±0.37)%, and in the negative control (NC) group were (15.54±1.46)%, (13.84±1.68)%, (9.94±3.01) and (5.50±0.99)%, respectively. Differences between the two groups at all effector-target ratios were statistically significant (t=19.402, 12.400, 7.093 and 9.842, all P<0.01). Moreover, the expression of dNK killing-related factor granzyme B in the siCLEC2D group was higher than that in the NC group. (3) Compared with the normal pregnancy group, the RSA group showed decreased CD161 expression and increased killing capacity of dNK cells, but no significant difference in CLEC2D expression.@*Conclusions@#At early pregnancy, CLEC2D on EVT cells can interact with CD161 on dNK cells, which inhibits the cytotoxicity of dNK cells and induces immune tolerance at the fetal-maternal interface. Decreased expression of CD161 in decidua results in increased cytotoxicity of dNK cells, which may be one of the causes of immune rejection in RSA.

Regulatory effect of CLEC2D-CD161 interaction on killing capacity of decidual natural killer cells / 中华围产医学杂志

Objective To investigate the regulatory effect of CLEC2D-CD161 interaction on killing capacity of decidual natural killer (dNK) cells during early pregnancy and its association with the incidence of recurrent spontaneous abortion (RSA). Methods Decidua tissues were collected from normal pregnancies (n=16) and RSA cases (n=6) at 6-10 gestational weeks in the Department of Obstetrics and Gynecology of Peking University Third Hospital from October 2018 to May 2019. (1) Expressions of CLEC2D and CD161 in decidua from early pregnancy were detected using immunofluorescence. (2) Primary dNK cells were isolated from decidua from early pregnancy. dNK cells pre-treated with CD161 antibody (blocking CD161, B-CD161) were co-cultured with JEG-3 cells which were knocked-down by CLEC2D small interfering RNA (siCLEC2D), followed by killing capacity assessment of dNK cells by cytotoxicity assay and determination of expressions of related molecules by quantitive real-time polymerase chain reaction. (3) Western blot and flow cytometry were used to detect the expression of CLEC2D and CD161 in decidua tissues. Cytotoxicity assay was performed to analyze the killing capacity of dNK cells. T test was used for statistical analysis between normal and RSA cases. Results (1) CLEC2D was mainly expressed in extravillous trophoblast (EVT) cells and CD161 was mainly detected in dNK cells. CD161-positive dNK cells and CLEC2D-positive EVT cells were adjacently located in decidua tissues allowing their interaction. (2) Cytotoxicity assay suggested that CD161 blocking in dNK cells or CLEC2D knockdown in JEG-3 cells could enhance the cytotoxicity of dNK cells. The target cell lysis rates at the effector-target ratios of 40 ∶ 1, 20 ∶ 1, 10 ∶ 1 and 5 ∶ 1 in B-CD161 group were (59.12±4.56)%, (25.96±5.44)%, (13.60±8.94)% and (12.53±8.94)%, and in IgG control group were (20.01±1.96)%, (8.51±1.32)%, (3.24±0.75)% and (3.82±1.92)%, respectively. There were significant differences between the two groups at the effector-target ratios of 40∶1 (t=13.922, P<0.01) and 20∶1 (t=5.403 P<0.05), but not at 10∶1 or 5∶1 (P>0.05). The target cell lysis rates at the effector-target ratios of 40∶1, 20∶1, 10∶1 and 5 ∶ 1 in si-CLEC2D group were (43.37±2.01)%, (32.99±2.08)%, (23.47±1.36)% and (11.48±0.37)%, and in the negative control (NC) group were (15.54±1.46)%, (13.84±1.68)%, (9.94±3.01) and (5.50±0.99)%, respectively. Differences between the two groups at all effector-target ratios were statistically significant (t=19.402, 12.400, 7.093 and 9.842, all P<0.01). Moreover, the expression of dNK killing-related factor granzyme B in the siCLEC2D group was higher than that in the NC group. (3) Compared with the normal pregnancy group, the RSA group showed decreased CD161 expression and increased killing capacity of dNK cells, but no significant difference in CLEC2D expression. Conclusions At early pregnancy, CLEC2D on EVT cells can interact with CD161 on dNK cells, which inhibits the cytotoxicity of dNK cells and induces immune tolerance at the fetal-maternal interface. Decreased expression of CD161 in decidua results in increased cytotoxicity of dNK cells, which may be one of the causes of immune rejection in RSA.

Ratio of transfer cesarean section after trial of labor and maternal-fetal adverse outcomes based on Robson classifications / 中华妇产科杂志

Objective To investigate the ratio of transfer cesarean section after trial of labor and maternal-fetal outcomes based on Robson classifications.Methods The delivery data by cesarean section in Third Affiliated Hospital of Guangzhou Medical University from January 1st,2009 to December 31st,2015 (gestational age ＞28 weeks and newborn birth weight ＞1 000 g) were retrospectively collected.The ratio of transfer cesarean section after trial of labor and maternal-fetal adverse outcomes were analyzed by weighted adverse outcome score in different Robson classifications.Results (1) The highest ratio of transfer cesarean section after trial of labor was classification 9 (all abnormal lies,including previous cesarean section and breech were excluded) reached 47.31％ (431/911),followed by classification 2 (nulliparous women with a single cephalic pregnancy,＞37 weeks gestation who had labour induced) accounted for 44.90％(409/911).(2)The tops of weighted adverse outcome score of transfer cesarean section after trial of labor were classification 10 (single cephalic pregnancy at ＜37 weeks gestation,including women with previous cesarean delivery) 24.55,classification 5 (single cephalic pregnancy multiparous women,with at least one previous cesarean delivery,＞37weeks gestation) 3.64.Conclusion Carefully evaluating the delivery mode and emphasizing the intrapartum management in nulliparous women with a single cephalic pregnancy,at ＞ 37 weeks gestation who had labour induced and trial of labor after cesarean section is essential to reduce the risk of adverse outcomes in transfer cesarean section after trial of labor.

Risk factors and sonographic findings associated with the type of placenta accreta spectrum disorders / 中华妇产科杂志

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.

Prevention and management of severe maternal morbidity in China / 中华围产医学杂志

Maternal mortality rate in China remains higher than that in developed countries despite its remarkable reduction in recent years. Preliminary studies suggest that maternal mortality rate is associated with the incidence of severe maternal morbidity. Therefore, researches focusing on prevention and management of critial maternal cases is of great importance to reduce maternal mortality rate.