Analysis of maternal and fetal outcomes and establishment of prediction model of vaginal delivery in pregnant women with pre-eclampsia complicated with fetal growth restriction.

OBJECTIVE: This study aimed to analyze the maternal and fetal outcomes of pregnant women with pre-eclampsia (PE), complicated with fetal growth restriction (FGR), and establish a prediction model of vaginal delivery to guide the selection of the delivery mode. PATIENTS AND METHODS: The study included 208 pregnant women with PE complicated with FGR. Of them, 49 patients were in the vaginal delivery group, and 159 patients were in the cesarean section group. The relevant maternal and fetal outcomes were analyzed. Patients were randomly divided into the training sample group and the test group with a ratio of 2:1. The three-layer neural network was used to select 24 maternal and infant outcome factors as the input nodes of the neural network to build a vaginal delivery prediction model. RESULTS: Results showed that the gestational age, the highest systolic and diastolic blood pressure, body weight, body length, and placental weight of the newborns in the vaginal delivery group were significantly higher than those in the cesarean section group. Incidence of preterm birth, amniotic fluid grade III, oligohydramnios, and severe small-for-gestational-age (sSGA) neonates were significantly lower in the vaginal delivery group compared to the cesarean section group (p < 0.05). A three-layer neural network delivery prediction model was constructed, and the accuracy rate of fitting with test samples was 91.80%. CONCLUSIONS: There is no significant difference in the incidence of maternal and fetal complications in PE complicated with FGR in different delivery methods. The three-layer neural network prediction model has good prediction ability for vaginal delivery of PE complicated with FGR and may be applied in clinical practice.

[Regional analysis of high risk factors of hypertensive disorders in pregnancy with organ or system impairment].

Objective: To explore the influencing factors of pregnancy-induced hypertensive disorders in pregnancy (HDP) with organ or system impairment in pregnant women, and to analyze and compare the differences of HDP subtypes in different regions of China. Methods: A total of 27 680 pregnant women with HDP with complete data from 161 hospitals in 24 provinces, autonomous regions and municipalities were retrospectively collected from January 1, 2018 to December 31, 2018. According to their clinical manifestations, they were divided into hypertension group [a total of 10 308 cases, including 8 250 cases of gestational hypertension (GH), 2 058 cases of chronic hypertension during pregnancy] and hypertension with organ or system impairment group [17 372 cases, including 14 590 cases of pre-eclampsia (PE), 137 cases of eclampsia, 2 645 cases of chronic hypertension with PE]. The subtype distribution of HDP in East China (6 136 cases), North China (4 821 cases), Central China (3 502 cases), South China (8 371 cases), Northeast China (1 456 cases), Southwest China (2 158 cases) and Northwest China (1 236 cases) were analyzed. By comparing the differences of HDP subtypes and related risk factors in different regions, regional analysis of the risk factors of HDP pregnant women with organ or system impairment was conducted. Results: (1) The proportions of HDP pregnant women with organ or system impairment in Northeast China (79.05%, 1 151/1 456), Central China (68.42%, 2 396/3 502) and Northwest China (69.34%, 857/1 236) were higher than the national average (62.76%, 17 372/27 680); the proportions in North China (59.18%, 2 853/4 821), East China (60.85%, 3 734/6 136) and South China (59.56%, 4 986/8 371) were lower than the national average, and the differences were statistically significant (all P<0.05). (2) Univariate analysis showed that the proportions of primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history in the hypertension with organ or system impairment group were higher than those in the hypertension group, and the differences were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history were independent risk factors for HDP pregnant women with organ or system impairment (all P<0.05). (3) Primipara: the rates of primipara in Northeast China, North China and Southwest China were higher than the national average level, while those in South China, Central China and Northwest China were lower than the national average level. Non-Han nationality: the rates of non-Han nationality in Northeast China, North China and Northwest China were higher than the national average, while those in East China, South China and Central China were lower than the national average. Non-urban household registration: the rates of non-urban household registration in Northeast China, North China, and Southwest China were lower than the national average, while those in East China, Central China were higher than the national average. Irregular prenatal examination: the rates of irregular prenatal examination in North China, South China and Southwest regions were lower than the national average level, while those in Northeast China, Central China and Northwest China were higher than the national average level. History of PE: the incidence rates of PE in Northeast China, North China, South China and Southwest China were lower than the national average level, while those in Central China and Northwest China were higher than the national average level. Conclusions: Primiparas, non-Han, non-urban household registration, irregular prenatal examination, and PE history are risk factors for HDP pregnant women with organ or system impairment. Patients in Northeast, Central and Northwest China have more risk factors, and are more likely to be accompanied by organ or system function damage. It is important to strengthen the management of pregnant women and reduce the occurrence of HDP.

The effect of cold exposure on the levels of glucocorticoids, 11-hydroxysteroid dehydrogenase 2, and placental vascularization in a rat model.

OBJECTIVE: Cold exposure (CE) before birth is one of the initial stressors that may impact mammalian pregnancy, changing placental and fetal development and affecting the health of the offspring. While glucocorticoids (GCs) participate in the body's response to the stress of CE, the specific mechanisms of their action are unclear. This study aims to determine the effect of CE stress on the placenta and to test whether stress, caused by cold exposure in pregnancy impairs fetal development by changing placental angiogenesis via excessive GC expression. MATERIALS AND METHODS: CE rat model was created by exposing 30 SD rats to cold preconception, or during the first, second, and third weeks of pregnancy. Serum cortisol and soluble fms-like tyrosine kinase-1 (sFlt-1) expression levels, physiological index changes (food intake, body weight change and blood pressure), and pregnancy outcomes (fetal rat weight, number of live fetal rats, and placental weight) were collected at baseline and at different time points after the conception. Protein expression levels of 11 ß-hydroxysteroid dehydrogenase 2 (11ß-HSD2), glucocorticoid receptor, vascular endothelial growth factor A (VEGF-A), placental growth factor (PIGF), and sFlt-1 in placental tissues were measured by western blotting. Cytokeratin (CK) and laminin (LN) in trophoblasts, and α-actin in vascular smooth muscle of the spiral arteries of pregnant rats after the systemic cold treatment were assessed by immunofluorescence and visualized by fluorescent microscopy. To test the effect of 11ß-HSD2 levels on the placental recasting, human first-trimester extravillous trophoblast cells (HTR8/SVneo) underwent knockdown using specific 11ß-HSD2 siRNA constructs.  Expression levels of 11ß-HSD2 were analyzed by quantitative real-time PCR (qPCR) and into HTR8 cells, and the expression levels of the 11ß-HSD2 gene in each group were measured using qPCR. Cell migration and invasion was assessed by Transwell migration assay, and sFlt-1 levels in HTR8 cells were measured by ELISA. RESULTS: CE pre-conception led to consistently increasing serum corticosterone and sFlt-1 levels throughout pregnancy, and persistently increased diastolic blood pressure (DBP) in rat CE model compared to control animals. CE during the second week of gestation (Gp.3) was associated with significantly lower placental weight (p=0.0003). Cold exposure in the third week (Gp.4) was associated with significantly (p=0.001) lower fetal weight. CE pre-conception was associated with significantly decreased placental levels of 11ß-HSD2, glucocorticoid receptor, VEGF-A, PIGF, and sFlt-1 proteins and α-actin compared to the control group. Silencing 11ß-HSD2 by siRNA led to reduced cell migrations and invasion, and markedly increased expression levels of sFlt-1 in HTR8/SVneo cells (p<0.05). CONCLUSIONS: Pre-conception cold exposure and during early pregnancy leads to increased GCs levels and impaired placental 11ß-HSD2 activity. We suggest that the subsequent 11ß-HSD2-induced increase in the sFlt-1expression during early pregnancy may affect placental vascular remodeling and change placental morphological structure and function.

Effect of induction of labor on maternal and perinatal outcomes in low-risk singleton pregnancies: a retrospective case-control study.

OBJECTIVE: The aim of the study was to investigate the effect of induction of labor on maternal and fetal outcomes. PATIENTS AND METHODS: This retrospective case-control study included 4386 pregnant women with low-risk singleton pregnancies who underwent regular prenatal examination and successful vaginal delivery at ≥41 weeks and 0 days of gestation in Fujian Maternal and Child Health Hospital between January 2014 and December 2018. Clinical data of women were retrospectively divided into the induction of labor group (2007 cases) and spontaneous onset of labor group (2361 cases) based on the mode of labor initiation. Two-sample independent t-test and χ2 tests were used to analyze the differences in clinical characteristics, such as maternal age and parity between the two groups. RESULTS: The induction of the labor group had a significantly longer total duration of labor (9.37±5.37 vs. 8.82±5.13 h; p<0.001), more postpartum blood loss (219.18±188.32 vs. 199.95±124.69 mL; p=0.01) and a significantly higher incidence of severe postpartum hemorrhage (PPH) comparing to the spontaneous onset of labor group [0.8% (16/2007) vs. 0.33% (8/2361); p=0.041]. However, no significant difference was found in the neonatal outcomes. After adjusting for age, induction of labor in nulliparous women was more likely to lead to PPH than the spontaneous onset of labor [2.74% (55/2007) vs. 1.65% (39/2361); odds ratio=1.557; 95% confidence interval: 1.039-2.332; p<0.05]. CONCLUSIONS: Induction of labor increases the duration of labor and postpartum blood loss, especially in primary parturient, leading to an increased risk of PPH. This increase may be related to the overall higher duration of labor, associated with IOL. Therefore, low-risk nulliparous women should try to avoid induction of labor without medical indications.

[Cone-beam CT analysis of the correlation between incisor root resorption rate and tooth movement index in adult patients with fixed orthodontics appliance].

Objective: To analyze the correlation between the root resorption rate and tooth movement of the maxillary and mandibular incisors before and after orthodontic treatment in adult patients using cone-beam CT (CBCT), and to explore the related factors that affect the apical root resorption. Methods: In this retrospective study, 23 adult patients with classⅠor class Ⅱ division 1 malocclusion [2 males and 21 females, mean age (23.4±6.3) years, treatment time (2.1±0.7) years] who received orthodontic treatment with fixed appliance in Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital from January 2017 to June 2021 were enrolled. Full-column CBCT examination was performed before and after treatment. A three-dimensional model was established to observe and record the volume of the maxillary and mandibular central and lateral incisors before and after treatment. The change of the incisal edge, the angle of rotation of the incisal edge, and the direction of the long axis of the tooth were also measured. The root resorption in each tooth before and after treatment was compared, and the root resorption rate was calculated. Pearson correlation analysis was performed on the root absorption rate before and after treatment with age, treatment time and tooth movement. Results: After treatment, the tooth volume of the maxillary and mandibular central and lateral incisors decreased significantly (P<0.01). The root absorption volumes were (20.2±6.0) mm3 and (11.2±4.7) mm3 in maxillary central and lateral incisors, and (14.7±4.6) mm3 and (14.8±5.0) mm3 in mandibular central and lateral incisors, respectively. The root absorption rates were (9.49±1.75)% and (9.13±3.24)% in maxillary central and lateral incisors, and (8.56±3.43)% and (9.13±3.24)%, in mandibular central and lateral incisors, respectively (F=0.56, P=0.640). The root resorption rate of maxillary central incisors had a weak positive correlation with the change of sagittal distance of incisal edge (r=0.36, P=0.015). The root resorption rate of mandibular central incisors had a moderate positive correlation with the vertical movement distance (r=0.48, P=0.001). The root resorption rate of mandibular lateral incisors was weakly positively correlated with the vertical movement of incisal edge and the treatment time (r=0.35, P=0.016; r=0.34, P=0.021), and was moderately positively correlated wit the change of sagittal movement of incisal edge (r=0.44, P=0.002). Conclusions: During orthodontic treatment, both maxillary and mandibular incisors had a certain degree of root resorption, which was related to sagittal and vertical movement of the incisors and the time of orthodontic treatment.

A rapid detection of tomato yellow leaf curl virus using recombinase polymerase amplification-lateral flow dipstick assay.

Tomato yellow leaf curl disease which is caused by Tomato yellow leaf curl virus (TYLCV) is economically important and a widely spread tomato disease in China. Rapid and accurate detection methods are important in the control TYLCV. Here, a rapid method was developed to identify TYLCV on the basis of recombinase polymerase amplification (RPA) that can be visualized in 5 min using lateral flow dipsticks. The sensitivity and the specificity of this method were evaluated. This method can detect 0·5 pg DNA after 30 min at 37°C without any expensive instrumentation. In addition, it showed higher sensitivity than a PCR method when purified DNA was used. Moreover, the TYLCV was specifically detected, whereas other viruses infecting tomato produced negative results. The crude tomato extracts used in this assay has potential application in minimally equipped plant clinic laboratories. This method will facilitate the early and rapid detection of TYLCV for the timely application of control measures.

[Comparative analysis of high risk factors between early-onset pre-eclampsia and late-onset pre-eclampsia].

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/m2 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/m2 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/m2 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.

[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.

Scoring system to predict the success rate of external cephalic versions and determine the timing of the procedure.

OBJECTIVE: We aimed to examine the prenatal clinical characteristics of women with single pregnancies undergoing external cephalic version (ECV) without anesthesia, develop a novel scoring system for predicting the ECV success rate, and demonstrate that this scoring system can be used to individualize the timing of ECV attempts. PATIENTS AND METHODS: We enrolled 270 women who underwent ECV without anesthesia at 37-40 weeks of gestation in the Fujian Maternity and Child Health Hospital from 2016 to 2019 and divided them into two ECV outcome groups (success vs. failure). We identified five clinical features (the fetal buttocks' station, the sum of the fundal height and station, the fetal head location, and whether the fetal head or buttocks could be grasped) as independent factors affecting the ECV success rate, and we scored them using a regression coefficient. RESULTS: Women with scores of 0-3 points had ECV success rates, vaginal delivery rates, and delivery gestational ages at 16.67%, 16.67%, and 38.88 weeks, respectively; those with scores of 4-6 points had ECV success rates, vaginal delivery rates, and delivery gestational ages at 65.75%, 58.90%, and 39.62 weeks, respectively; and those with scores of 7-9 points had ECV success rates, vaginal delivery rates, and delivery gestational ages at 93.71%,74.83%, and 40.00 weeks, respectively. CONCLUSIONS: The ECV success and vaginal delivery rates increased with the score, and the delivery gestational age showed an initial increase. To optimize the ECV procedure and reduce the hospital burden, this scoring system should be used routinely to predict the ECV success rate and determine the timing of ECV attempts.

Relation of meconium-stained amniotic fluid and postpartum hemorrhage: a retrospective cohort study.

OBJECTIVE: Postpartum hemorrhage (PPH) is a major cause of maternal mortality and morbidity worldwide. The purpose of this study was to evaluate if meconium-stained amniotic fluid (MSAF) is a risk factor for PPH after vaginal delivery. PATIENTS AND METHODS: We retrospectively analyzed medical records of all patients who had a vaginal delivery at Fujian Provincial Maternity and Children's Hospital, between 1st January 2013 to 31st December 2018. Women with cesarean deliveries, multiple pregnancies, abnormal coagulation profile, and those with concomitant liver or kidney disorders were excluded. Patients were classified into MSAF (n=13686) and clear amniotic fluid (AF) (n=41511) groups. RESULTS: The incidence of PPH was significantly higher at 2.7% (370/13686) in the MSAF group as compared to 2.18% (904/41511) in the clear AF group (p=0.0004). There was no difference in the incidence of severe PPH between the two groups. Statistically significant difference in the incidence of PPH between MSAF and clear AF was seen in the maternal age groups of 30-34 and 35-39 years, gestational age>40weeks and >3 gravidity (p<0.05). CONCLUSIONS: Our study demonstrates that MSAF is a significant risk factor for minor and moderate PPH. Presence of meconium could therefore alert clinicians to expect PPH and make arrangements for further patient management. Further basic research is required to evaluate the mechanism by which meconium influences the incidence of PPH.

A new predicting model of preeclampsia based on peripheral blood test value.

OBJECTIVE: To identify laboratory markers among platelet indices, coagulation parameters, blood lipid parameters, and liver/kidney function variables that can be used to predict preeclampsia. PATIENTS AND METHODS: We studied records of 568 women with preeclampsia, gestational hypertension (GH), or normal term pregnancies hospitalized in the Obstetrics Department of the Fujian Maternal and Child Health Hospital from September 2014 to September 2018. We divided the patients' records into three groups (216 with preeclampsia, 136 with gestational hypertension, and 216 with normal pregnancies). We conducted retrospective analyses to compare variable measurements between the groups and find correlations. We looked into maternal pre-onset platelet indices, coagulation parameters (thrombin time [TT], fibrinogen [FIB]), biochemical parameters (total cholesterol [TC], triglycerides [TG], high-density lipoproteins [HDL], alanine transaminase [ALT], serum creatinine [CRE], blood urea nitrogen [BUN], uric acid [UA]), maternal complications, and perinatal outcomes. In addition to our statistical analysis, we trained a back-propagation (BP) neural network to identify the strongest predictors of preeclampsia. RESULTS: We found significant differences among the groups in terms of values for PLT, MPV, PDW, PLCR, TT, FIB, TG, LDH, BUN, and others. After adjusting for confounding factors in a multivariate ordered logistic regression model, we found that mean values for MPV, BUN, TG, and LDH can independently predict the risk of preeclampsia (the OR values were 1.858, 1.583, 1.104, and 1.020, respectively), the C-index (concordance statistic) was 0.73. Also, our BP neural network derived ALB, MPV, BUN, LDH and TG as the strongest predictors of preeclampsia. CONCLUSIONS: MPV, TG, LDH, and BUN can help establish the risk for the development of preeclampsia to apply active measures and improve maternal and perinatal outcomes. The BP neural network can be used to study predictive models of preeclampsia.

[Etiology and molecular-epidemiological characteristics of viral meningo-encephalitis in Zhejiang province, 2002-2018].

Objective: To understand the pathogens and molecular-epidemiologic characteristics of viral meningo-encephalitis in Zhejiang province during 2002 to 2018. Methods: All the samples were collected from suspected patients admitted to the hospitals under the monitoring program. Of the total samples, 2 173 were cerebrospinal fluids while the other 455 were stool specimens. Cerebrospinal fluid (CSF) samples were subject to real-time qPCR for the detection of Human enterovirus (HEV), Mumps virus (MuV), Herpes simplex virus (HSV), Cytomegalovirus (CMV) and Japanese encephalitis virus (JEV). Stool sample were subject to real-time qPCR for HEV. ELISA was used to detect the IgM antibodies in CSF, in the 5 kinds of virus mentioned above. VP1 genes from all RNA-positive specimen were amplified, sequenced, for typing and for evolution analysis. Results: 871 (40.1%) of the 2 173 samples were detected as HEV nucleic acid positive during 2002 to 2018. 654 (38.1%) of the 1 718 CSF sample were HEV nucleic acid positive while 217 (47.7%) of the 455 stool sample were HEV nucleic acid positive. Among the total positive nucleic acid sample, 670 of them were VP1 sequence positive, including 5 HEV-A and 665 HEV-B. There were 23 HEV serotypes, including Coxsackievirus (CV) CVA4, CVA6, CVA9, CVA10, CVB1-5, Echovirus (EchoV; E) E3, E4, E6,E7, E9, E11, E14, E16, E18, E21, E25, E30, E33 and EV-71. The top three serotypes went to E30, E6 and CVB5. These three serotypes presented enhanced viral activity in every several years. 795 CSF samples were detected as virus nucleic acid positive, including 374 HEV, 6 MuV, 5 HSV and 5 CMV, from 2012 to 2015 and in 2018. 5 kinds of IgM antibodies were detected simultaneously in 368 CSF samples, including 2 HEV positive, 6 JEV positive and 1 MuV positive for 5 viruses, respectively. Except for EV-71, there were 517 EchoV and 152 CV viruses presented, with the ratio of 3.4∶1. These two kinds of viruses alternately changed for each predominant epidemic strains in every 3-5 years. Based on VP1, results from the phylogenetic tree showed that HEV from Zhejiang province clustered into HEV-A and HEV-B clades respectively. E30 developed both h and i sub-genotypes. Conclusions: HEV-B seemed the main pathogen for viral meningo-encephalitis in Zhejiang province. Ratio of positive detection on EchoV was significantly higher than that on CV. These two kinds of virus alternately presented changing tendency in every several years. Predominant epidemic strains E30, CVB5 and E6 were presenting enhanced viral activity, also in every several years. High correlation was found in both HEV viral activity from the surveillance sites and in time line of the viral meningo-encephalitis outbreaks.

[Value of lenvatinib for the treatment of advanced hepatocellular carcinoma].

Objective: To observe the safety and efficacy of lenvatinib for the treatment of medium-advanced hepatocellular carcinoma. Methods: A total of 36 patients with medium-advanced hepatocellular carcinoma from the First Medical Center of the Chinese PLA General Hospital were retrospectively analyzed from January 2018 to May 2019. All patients had shown tumor progression after at least 2 sessions of TACE. The patients were consisted of 30 males and 6 females with age range of 35 to 76 (54±10) years. Patients received orally administered lenvatinib at a dose of 12 mg once daily for patients ≥ 60 kg and 8 mg once daily for patients<60 kg. According to modified RECIST criteria the tumor response, disease control rate, overall survival and progression free survival were evaluated once every 6-8 weeks. The adverse events were recorded. Results: No patient was in complete response, 2 cases (5.7%) in partial response, and 5 cases (14.3%) in stable disease, respectively. Disease control rate was 20.0% (7/35), the overall survival was 11.5 months, and the progression free survival was 5.3 months. The overall incidence of adverse events was 66.7% (24/36). The most frequent adverse events were hypertension, proteinuria, hand-foot skin reaction and abdominal distension. Conclusion: Lenvatinib can extend the overall survival in a percentage of medium-advanced hepatocellular carcinoma patients who were unresectable and refractory to TACE. Although the incidence of adverse events is high, most of them are mild and reversible.

[Progression of diagnosis and treatment in pediatric colorectal carcinoma].

Colorectal carcinoma (CRC) is the third most common malignancy in adults. Pediatric colorectal carcinoma (PCRC) is a rare non-embryonal tumor with a significantly lower incidence compared to adults. The clinical manifestations of PCRC are not typical, and pediatricians usually have no enough experience in diagnosis and treatment. Therefore, early diagnosis is extremely difficult, which would always lead to late clinical stages when diagnosis is made. At present, the pathogenesis of PCRC is still not clear, and many countries have started to carry out researches at the level of genes, molecules and cells. In both tumor primary tumors and distant metastases, PCRC has obvious difference in distribution from adults, and the proportion of pathological type of mucous adenocarcinoma (including the signet ring cell carcinoma) was significantly higher than that of adults. Although treated according to adult colorectal cancer guidelines, PCRC has been unable to achieve ideal efficacy with poor prognosis and lower long-term survival rate. The purpose of this paper is to summarize the epidemiological characteristics, pathogenesis, clinical symptoms, pathological types, treatment and prognosis of colorectal cancer in children by reviewing the latest literatures at home and abroad.

Transarterial embolisation with bleomycin and N-butyl-2-cyanoacrylate -Lipiodol mixture for symptomatic polycystic liver disease: preliminary experience.

AIMS: To evaluate the therapeutic effect and safety of transarterial embolisation using a bleomycin-Lipiodol mixture and N-butyl-2-cyanoacrylate (NBCA)-Lipiodol mixture (BNL) for the treatment of polycystic liver disease (PLD). MATERIALS AND METHODS: From June 2012 to July 2018, a total of consecutive 14 symptomatic patients (13 women and 1 man; mean age, 49.3±9.9 years) with PLD were referred and underwent transcatheter arterial embolisation (TAE) with BNL. RESULTS: Technical success was achieved in all cases. PLD-related severe symptoms were improved remarkably in 13 of the treated patients. The mean maximum abdominal circumference decreased significantly from 100.6±9.4 to 94.9±9.1 cm (p<0.01). The total liver volume decreased significantly compared with pre-TAE in 13 patients at 6-12 months after TAE. It decreased from 9,776±2,219 to 8,303±2,009 cm3 (p<0.01). There were no major complications associated with the procedure. CONCLUSION: TAE with the bleomycin-Lipiodol mixture and NBCA-Lipiodol mixture may be an effective method for treating symptomatic PLD patients, with improvement of symptoms and shrinkage of cyst volume.

Effect miR-214-3p on proliferation and apoptosis of breast cancer cells by targeting survivin protein.

OBJECTIVE: Studies showed that microRNAs (miRs) play an important role in the development of breast cancer. It has been shown that there were significant differences between the expression levels of serum miR-214-3p in breast cancer patients and healthy controls. Since survivin is involved in cell cycle and apoptosis, this study aims to investigate the effect of miR-214-3p on the proliferation and apoptosis of breast cancer cells. MATERIALS AND METHODS: Dual-Luciferase reporter system was used to validate the cell cycle-related target gene survivin. miRanda and TargetScan were used to predict miR-214-3p target genes. Lipofectamine 2000 was used to transfect the miR-214-3p mimics, miR-NC into the MCF-7 cells. The quantitative Real Time-PCR (qRT-PCR) was used to detect the expression levels of miR-214-3p and survivin. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was used to examine the cell proliferation of breast cancer cells. The flow cytometry assay was used to evaluate the apoptosis of breast cancer cells. RESULTS: Dual-Luciferase reporter assay showed that cells co-transfected with wild-type vector and miR-214-3p mimics had significant lower ratios of hRluc/Luc fluorescence compared to that of the control group (p<0.05). The expression level of miR-214-3p was increased along with the increase of time after transfection, whereas the expression level of survivin mRNA was decreased along with the increase of time post transfection. This result suggests that miR-214-3p regulates the mRNA expression of survivin. Transfection of miR-214-3p inhibitor increased the proliferation of MCF-7 cells and transfection of miR-214-3p mimics decreased the proliferation of MCF-7 cells compared to control group (p<0.05). CONCLUSIONS: Survivin gene is a downstream target of miR-214-3p in breast cancer cells. The expression of miR-214-3p and survivin is correlated with the proliferation and apoptosis of breast cancer cells.

SHH expression in placental tissues and trophoblast cell oxidative stress injury during preeclampsia.

OBJECTIVE: To assess the association between Sonic hedgehog (SHH) protein expression levels on placental tissues and the presence of preeclampsia and to assess oxidative stress in cultured trophoblast cells from placentas of women with preeclampsia treated under different conditions. PATIENTS AND METHODS: We enrolled 30 pregnant women with early-onset preeclampsia (<34 weeks), 30 with late-onset preeclampsia (≥34 weeks), and 60 healthy pregnant women with early or late gestational ages for two control groups. We used ELISA tests to measure individual serum SHH levels. Also, we used real-time PCR, and Western blotting to detect Shh transcript and protein levels in placental tissues, respectively, and immunohistochemistry to localize the protein in placental tissues. We isolated trophoblast cells from placentas and cultured them in vitro under different conditions to compare oxidative stress injury and apoptosis rates between them. RESULTS: The mean serum SHH levels in early and late preeclampsia groups were similar (p>0.05). Placentas of women with and without preeclampsia both expressed SHH protein mainly in syncytiotrophoblast cytoplasms. The mean placental SHH protein expressions in both women with early-onset and late-onset preeclampsia were significantly higher than that in the women of the late gestational age control group (p<0.05). The mean Shh mRNA abundances in early-onset and late-onset preeclampsia placentas were significantly higher than that in the late gestational age control placentas (p<0.05). The placental mitochondria oxidative stress injury was significantly higher in the preeclampsia than in the control group (p<0.05). The oxidative stress injury and apoptosis of trophoblast cells were higher in preeclampsia groups than in the late gestational age control group (p<0.05). Trophoblast cells treated with SHH serum had significantly lower oxidative stress than the same cells grown in the presence of preeclamptic serum (p<0.05). CONCLUSIONS: The expression of Shh in placental tissues is associated with the oxidative stress mechanism during preeclampsia.

[Transarterial chemoembolization with bleomycin treatment for moderate-advenced hepatocellular carcinoma].

Objective: To investigate the safety and efficacy of transarterial chemoembolization (TACE) using bleomycin for the treatment of medium-advanced hepatocellular carcinoma (HCC). Methods: Between December 2015 and December 2017, a total of 160 patients from the Chinese PLA General Hospital with moderate-advanced HCC whose diagnoses were confirmed by pathology or clinical imaging and were in accord with the Barcelona Clinic Liver Cancer (BCLC) staging criteria were prospectively analyzed.All patients had shown persistent viable tumor or tumor progression after at least 2 sessions of TACE.All patients included 135 males and 25 females , age 35-74 (57±8)years, were randomly divided into two groups, the treatment group: TACE procedures consisted of bleomycin+ pirarubicin+ oxaliplatin+ fluorouracil, the control group: pirarubicin+ oxaliplatin+ fluorouracil, and according to modified RECIST criteria the tumor response was evaluated once every 4-6 weeks, survival analysis was performed, overall survival and progression free survival were evaluated.the adverse events were recorded. Results: Response rate of the treatment group was 27.5%(22/80), the median progression free survival(mPFS)was 5.8 months, and the median overall survival (mOS) was 8.1 months.Response rate of the control group was 7.5%(6/80), mPFS of 2.9 months, and mOS of 4 months.The differences in mPFS and in mOS between the two groups were statistically significant (P=0.009, 0.002 respectively), and no serious adverse occurred. Conclusion: It is suggested that transarterial chemoembolization with bleomycin is safe and effective for medium-advenced HCC.

[The safety and effect of transhepatic hilar approach for the treatment of bismuth type â ¢ and â £ hilar cholangiocarcinoma].

Objective: To compare the efficiency between the transhepatic hilar approach and conventional approach for the surgical treatment of Bismuth type Ⅲ and Ⅳ hilar cholangiocarcinoma. Methods: There were 42 consecutive patients with hilar cholangiocarcinoma of Bismuth type Ⅲ and Ⅳ who underwent surgical treatment at Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University from January 2008 to December 2013.The transhepatic hilar approach was used in 19 patients and conventional approach was performed in 23 patients.There were no differences in clinical parameters between the two groups(all P>0.05). The t-test was used to analyze the measurement data, and the χ(2) test was used to analyze the count data.Kaplan-Meier analysis was used to analyze the survival period.Multivariate COX regression analysis was used to analyze the prognosis factors. Results: Among the 19 patients who underwent transhepatic hilar approach, 3 patients changed the operative planning after reevaluated by exposing the hepatic hilus.The intraoperative blood was 300(250-400)ml in the transhepatic hilar approach group, which was significantly less than the conventional approach group, 800(450-1 300)ml(t=4.276, P=0.00 1), meanwhile, the R0 resection rate was significantly higher in the transhepatic hilar approach group than in the conventional approach group(89.4% vs. 52.2; χ(2)=6.773, P=0.009) and the 3-year and 5-year cumulative survival rate was better in the transhepatic hilar approach group than in the conventional approach group(63.2% vs. 47.8%, 26.3% vs. 0; χ(2)=66.363, 127.185, P=0.000). On univariate analysis, transhepatic hilar approach, intraoperative blood loss, intraoperative blood transfusion, R0 resection and lymph node metastasis were significant risk factors for patient survival(all P<0.05). On multivariate analysis, use of transhepatic hilar approach, intraoperative blood loss, R0 resection and lymph node metastasis were significant independent risk factors for patient survival(all P<0.05). Conclusion: The transhepatic hilar approach is the preferred technique for surgical treatment for hilar cholangiocarcinoma because it can improve accuracy of surgical planning, safety of operation, R0 resection rate and survival rate compared with the conventional approach.