Objective To evaluate the clinical significance and prognosis of tetus with lateral ventriculomegaly.Methods We retrospectively analyzed 92 singleton pregnant women who were antenatally diagnosed with fetal ventriculomegaly by ultrasound in genetic conselling clinics,Department of Gynaecology and Obstetrics,Nanfang Hospital,Southern Medical University between August 2007 and August 2010.All participants were divided into three groups according to the width of the lateral ventricles:group A (10.0-12.0 mm,n＝50),group B (12.1-14.9 mm,n=38) and severe ventriculomegaly group (≥15.0 mm,n=4).All fetuses were followed up.Chi-square test(or Fisher's exact test),Bonfferoni method,Mann Whitney or Kruskal-Wallis test were used for statistics.Results In group A,B and severe ventriculomegaly group,18％ (9/50),65.8％(25/38)and 3/4 of fetuses were complicated with structural malformation,respectively (x2 =22.934,P =0.000),and statistical significance were found only between group A and B (x2 =20.798,P=0.000).The incidences of fetal chromosomal aberration were 4.0％ (2/50),7.9％ (3/38)and 0/4 in the three groups,respectively (x2＝0.878,P ＝ 0.645).Eventually,all four cases with severe cerebral ventriculomegaly were terminated.Among cases of mild ventriculomegaly,63 women continued the pregnancy (48 in group A and 15 in group B).The intrauterine improvement of group B was poorerthan that of group A (Z=-3.317,P =0.001).Respectively,three,ten and two cases of ventriculomegaly deteriorated,stabilized and regressed in group B,and the corresponding figures were 3,15 and 30 in group A.In group A,the prognosis of fetus with non-isolated ventriculomegaly was poorer than that of fetus with isolated ventriculomegaly (Z=-2.631,P=0.009).For neonates 14 days after birth (n=62),the rates of normal neonatal behavioral neurological assessment (NBNA) scoring were respectively 93.8％ (45/48) and 71.4％ (10/14) for groups A and B with statistical difference (Fisher's exact test,P =0.040).Bayley scales of infant development (BSID) used to evaluate infants at 12-month-old revealed that the psychomotor developmental index (PDI) between group A and group B had statistical difference (8,26 and 1 case of good,moderate and poor development in group A; one,seven and three cases in group B; Z=-2.203,P=0.043).However,the mental developmental index (MDI) between group A and B had no statistical difference.Twenty babies among the survived ones received magnetic resonance imaging (MRI) examination.The results showed that lateral ventricle width regressed in nine babies (45.0％) and progressed in one baby (5.0％).Ten cases (50.0％) did not change.The change of ventriculomegaly after birth was related to BSID evaluation.Better prognosis of fetuses were found in those with regressed ventriculomegaly (P=0.033).Conclusions Fetuses with mild ventriculomegaly (10.0 12.0 mm) have a favorable outcome.Further investigations,such as fetal development,chromosomal examination,intrauterine infection screening and MRI if necessary,are suggested for fetus with ventriculomegaly.Moreover,intensive intrauterine and postnatal follow-up is recommended.

This study is to investigate the protection effect of schisandrin B (Sch B) against oxidation stress of HK-2 cells induced by cisplatin and the mechanisms involved. HK-2 cells were cultured and divided into different groups: solvent control group, cisplatin exposure group, positive group, Sch B treatment group. Cell viability and toxicity were evaluated by MTT and LDH assay. GSH level and SOD enzymes activities were also measured. DCFH-DA as fluorescence probe was used to detect ROS level by fluorescence microplate reader. Nrf2 translocation was detected by Western blotting. Real time Q-PCR was used to detect expressions of NQO1, HO-1 and GCLC mRNA level. The results showed that Sch B could significantly inhibit the decline of cell viability induced by cisplatin treatment (P < 0.05) and the protective effect was in a dose dependent manner. Furthermore, Sch B treatment significantly inhibited the increase of ROS level induced by cisplatin and reversed the decrease of GSH level (P < 0.05). When Sch B concentration was up to 5 micromol x L(-1), SOD enzyme activities were also enhanced significantly compared with that of the cisplatin group (P < 0.05). It was shown that Sch B could cause nuclear accumulation of Nrf2 in association with downstream activation of Nrf2 mediated oxidative response genes such as GCLC, NQO1 and HO-1. These results suggested Sch B could protect against the oxidative damage of HK-2 cells induced by cisplatin via the activation of Nrf2/ARE signal pathway.

Objective To study the local irritation of repeated intrathecal injection of Ziconotide Acetate,and to provide reference for irritancy evaluation ofintrathecal injection.Methods Sixteen New Zealand rabbits were assigned into two groupsat random:Control group and Ziconotide Acetate group,eight animals each group.Totally 50 μL saline or Ziconotide Acetate (100 μg/mL) were administrated by repeated lumbar intrathecal injection once daily for 7 d.Animal behavior was observed every day,and four animals in each group were sacrificed 2 d later after the last injection,the lumbar spinal cord was removed for histopathological examination and irritancy evaluation.The remaining animals were sacrificed for initancy evaluation 14 d later after the last injection.Results Only one animal died after anesthesia on day three in saline group,while no obvious adverse reactions were observed in other rabbits during the entire study,and no intrathecal irritant reactions of histopathological examination were found in both groups.The reversible minor mechanical damage was observed at the injection point,2 d after the last administration.Conclusion For 7 d repeated lumbar intrathecal injection in rabbits,no intrathecal irritant reactions observed in Ziconotide group,and the New Zealand rabbit could be used as a local irritation evaluation model.

Objective To investigate the mRNA expression and methylation status of IL-13 receptor(IL-13R)α1 gene in peripheral T lymphocytes of patients with systemic lupus erythematosus(SLE).Methods Venous blood samples were obtained from 10 SLE patients(5 in active phase,5 in inactive phase)and 6 normal human controls.CD4+ and CD8+ T cells were isolated from these samples via magnetic activated cell sorting(MACS).Real-time quantitative PCR was used to test the mRNA expression of IL-13Rα1 gene,and methylation specific PCR to detect the methylation status.Results The expression level of IL-13Rα1 mRNA was 2.224±0.251,1.712±0.132.and 1.104±0.044 in CD4+ T cells of active SLE patients,inactive SLE patients and controls,respectively;the difference between the three groups was statistically significant(all P＜0.05).The expression level of IL-13Rα1 mRNA in CD8+T cells was significantly higher in active SLE patients than that in the normal controls(1.672±0.142 vs 1.238±0.106,P＜0.05),while no difference was noted between inactive and active SLE patients or normal controls.The methylation index of IL-13Rα1 gene was 0.454±0.023.0.635±0.065.0.844±0.097 in CD4+T cells of active SLE patients,inactive SLE patients and normal controls,respectively,and the difference between the three groups was significant(all P＜0.05),while no significant difference was observed in the methylation index in CD8+T cells among these groups(P＞0.05).The IL-13Rα1 mRNA expression in CD4+T and CD8+T cells was positively correlated with SLE disease activity index(SLEDAI)score(r=0.79,0.76,P=0.007,0.02 respectively).A negative correlation was found between the methylation level Of IL-13Rα1 in CD4+T cells and SLEDAI score(r=-0.89.P＜0.0 1).as well as between the IL-13Rα1 mRNA expression and its methylation level(r=-0.84,P＜0.0 1).Conclusion The development of SLE may be related to the overexpression of IL-13Rα1 gene induced by DNA hypomethylation in T cells.

OBJECTIVETo investigate the implications of a prenatal diagnosis of single umbilical artery (SUA) for chromosomal abnormalities and neonatal outcomes.

METHODSFrom January, 2008 to June, 2012, color Doppler ultrasound identified 44 fetuses with SUA. Prenatal diagnoses with amniocentesis or umbilical blood sampling were subsequently ordered for routine chromosome karyotyping and the newborns were followed up for assessing the neonatal outcomes.

RESULTSOf all the 44 fetuses, 24 had uncomplicated SUA, and 20 had other concurrent abnormalities (including 8 with abnormal ultrasound soft indexes and 12 with chromosomal abnormalities). The two groups of fetuses showed significant differences in gestational weeks at delivery and incidence of chromosomal abnormalities but not in neonatal weight, placenta weight or APGAR score.

CONCLUSIONSFetuses with a prenatal diagnosis of SUA and other development abnormities need to undergo prenatal chromosomal examination. For fetuses with uncomplicated SUA, careful ultrasound examination is necessary to avoid missed diagnosis of potential congenital abnormalities.

Adult ; Chromosome Disorders ; diagnostic imaging ; genetics ; Female ; Fetus ; abnormalities ; Humans ; Karyotyping ; Pregnancy ; Pregnancy Trimester, Second ; Pregnancy Trimester, Third ; Single Umbilical Artery ; diagnostic imaging ; Ultrasonography, Prenatal ; Young Adult

Objective To investigate the role of miRNAs in maternal amniotic fluid exosomes in development of isolated ventriculomegaly(VM)in fetuses.Methods Amniotic fluid samples were collected from 9 cases of moderate isolated VM and 8 normal control cases to extract exosomal miRNA,and miRNA sequencing technique was used to identify differentially expressed miRNAs between the two groups.Three miRNAs with significant differential expression between the two groups,whose high expression was associated with VM,were selected for verification with RT-qPCR.Dual luciferase reporter assays were used to verify the regulatory effect of miR-122-5p on its predicted target genes AKT3 and CCDC88C.Gene ontology(GO)and KEGG pathway analyses were performed to explore the possible roles of the top 40 significant differential miRNAs in the pathophysiology of VM.Results We identified a total of 272 differentially expressed miRNAs in VM cases,including 43 up-regulated and 229 down-regulated miRNAs.The target genes of these differential miRNAs were associated with DNA and transcription factor binding,transmembrane transporter and nucleic acid binding transcription factor activity,and cell developmental process.These miRNAs were mostly enriched in the MAPK,cGMP-PKG and Wnt signaling pathways.Verification with RT-qPCR showed that miR-122-5p expression level was significantly lower in VM group than in the control group(P<0.05),which was consistent with miRNA sequencing results;let-7b-5p expression level was significantly lower in VM group,which was contrary to miRNA sequencing result.Dual luciferase reporter assays showed that miR-122-5p was not capable of regulating AKT3 or CCDC88C expressions.Conclusions The highly abundant differentially expressed miRNAs in maternal amniotic fluid exosomes play important roles in the occurrence of fetal VM possibly by regulating the MAPK,PI3K-Akt,Wnt and cGMP-PKG signaling pathways.

Objective To investigate the role of miRNAs in maternal amniotic fluid exosomes in development of isolated ventriculomegaly(VM)in fetuses.Methods Amniotic fluid samples were collected from 9 cases of moderate isolated VM and 8 normal control cases to extract exosomal miRNA,and miRNA sequencing technique was used to identify differentially expressed miRNAs between the two groups.Three miRNAs with significant differential expression between the two groups,whose high expression was associated with VM,were selected for verification with RT-qPCR.Dual luciferase reporter assays were used to verify the regulatory effect of miR-122-5p on its predicted target genes AKT3 and CCDC88C.Gene ontology(GO)and KEGG pathway analyses were performed to explore the possible roles of the top 40 significant differential miRNAs in the pathophysiology of VM.Results We identified a total of 272 differentially expressed miRNAs in VM cases,including 43 up-regulated and 229 down-regulated miRNAs.The target genes of these differential miRNAs were associated with DNA and transcription factor binding,transmembrane transporter and nucleic acid binding transcription factor activity,and cell developmental process.These miRNAs were mostly enriched in the MAPK,cGMP-PKG and Wnt signaling pathways.Verification with RT-qPCR showed that miR-122-5p expression level was significantly lower in VM group than in the control group(P<0.05),which was consistent with miRNA sequencing results;let-7b-5p expression level was significantly lower in VM group,which was contrary to miRNA sequencing result.Dual luciferase reporter assays showed that miR-122-5p was not capable of regulating AKT3 or CCDC88C expressions.Conclusions The highly abundant differentially expressed miRNAs in maternal amniotic fluid exosomes play important roles in the occurrence of fetal VM possibly by regulating the MAPK,PI3K-Akt,Wnt and cGMP-PKG signaling pathways.

Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40％of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated he-patic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and ther-apeutic targets for liver protection.

This study aims to investigate the value of pre-treatment computed tomography (CT) texture analysis in predicting therapeutic response of liver metastasis from colorectal cancer after combined targeting chemotherapy. A total of 82 patients with colorectal cancer liver metastases who underwent chemotherapy combined with targeted therapy (cetuximab) between March 2011 and October 2017 comprised this retrospective study population. According to the RECIST1.1, the best curative effect evaluation of patients was recorded. Complete response (CR) and partial response (PR) were assigned to the response group, and the stable disease (SD) and progressive disease (PD) were assigned to the non-response group. The CT texture analysis was based on the Omini-Kinetics software, and the three-dimensional (3D) texture analysis was performed on the marked lesion on portal phase. The differences of texture parameters between the response group and the non-response group were compared. The receiver operating characteristic (ROC) curves were depicted on the parameters which with statistically difference, to characterize value in predicting the response to target-combined chemotherapy. The differences of Entropy, Energy, Variance, std. Deviation, Quantile95 and sumEntropy between the two groups in pre-treatment lesions were significant ( < 0.05). And lesions with higher Entropy, lower Energy, higher Variance, higher std Deviation and higher sumEntropy seemed to indicate a better therapeutic response. When sumEntropy > 0.867, good diagnostic efficiency could be obtained, with sensitivity of 60.5% and specificity of 79.5%, respectively. In conclusion, texture parameters derived from baseline CT images of colorectal cancer liver metastasis have the potential value acting as imaging biomarkers in predicting tumor response to combined target chemotherapy.

OBJECTIVETo investigate the association between maternal serum neutrophil-lymphocyte ratio (NLR) and placental inflammatory response (PIR) in late pregnancy.

METHODSWe retrospectively analyzed the clinical and follow-up data of 478 pregnant women undergoing routine prenatal examination and delivery in our hospital in the year 2016. According to the placental pathological results, the women were divided into PIR group (238 cases) and control group (240 cases). The levels of serum inflammatory makers including leukocytes, neutrophils, lymphocytes, C-reactive protein (CRP) and NLR were compared between the two groups to analyze the association of these markers with PIR. Multivariate analysis was performed to identify the independent risk factors of PIR. Logistic regression model was established and the area under the receiver operating characteristic curve (ROC) was used for analyzing the prognostic value of these makers in late pregnancy.

RESULTSThe areas under the curve (AUC) of leukocytes, neutrophils, lymphocytes, CRP and NLR were 0.698 (95%: 0.485-0.766), 0.716 (95%: 0.453-0.783), 0.329 (95%: 0.228-0.431), 0.725 (95%: 0.677-0.765) and 0.801 (95%: 0.742-0.856), respectively. After adjusting the confounders, multivariate logistic regression analysis showed that preterm labor (OR=2.446, 95%: 1.003-4.590), premature rupture of membranes (OR=2.304, 95%: 1.049-4.161), NLR > 7 (OR=3.268, 95%: 2.071-6.920), and CRP > 15 mg/L (OR=2.137, 95%: 1.412-8.236) were independent risk factors for PIR.

CONCLUSIONSAn increased NLR in late pregnancy can serve as an effective indicator for predicting the risk of PIR.