Objective:To study the effects of arsenic exposure on neurological function including voluntary motor ability, anxiety, and short-term memory ability of rats, as well as its impact on the expression levels of synaptic function related genes such as neuropeptide 1 (NLGN1), glutamate receptor 2A (NR2A), and postsynaptic density protein 95 (PSD95).Methods:Forty 3-week-old male specific pathogen free (SPF) grade Wistar rats [weighing (453.97 ± 35.68) g] were selected and divided into four groups using a random number table: 0 (control group) and 2, 10, and 50 mg/L arsenic exposure groups, with 10 rats in each group. They were given deionized water and 2, 10, and 50 mg/L sodium arsenite solutions for 12 weeks, respectively. The open field experiment and Y-maze experiment were used to test the voluntary motor ability, anxiety, and short-term memory ability of rats. Nissl staining was used to observe the pathological damage of the hippocampus in the brain. Real time fluorescence quantitative PCR and Western blot were used to detect the mRNA and protein expression levels of NLGN1, NR2A, and PSD95 in the hippocampus, respectively.Results:The results of the open field experiment revealed that the horizontal movement distances of rats in the 2 and 10 mg/L arsenic exposure groups were reduced compared to the control group, the movement distances in the central area in the 2, 10, and 50 mg/L arsenic exposure groups were reduced compared to the control group, and the residence time in the central area in the 10 and 50 mg/L arsenic exposure groups was reduced compared to the control group ( P < 0.05). The results of Y-maze experiment showed that the retention time of new arms in rats of the 2 and 10 mg/L arsenic exposure groups was shorter than that in the control group ( P < 0.05). The pathological examination results of Nissl staining showed that the control group had abundant Nissl bodies in hippocampal tissues of the cytoplasm with intact neuronal structures, tightly arranged cells, appearing blue purple in color and clear visible nuclei. However, the number of Nissl bodies decreased, intercellular gaps increased, disordered arrangement increased, cytoplasmic staining was lighter, and nuclear shrinkage phenomenon increased in the hippocampal tissues of rats in the 2, 10 and 50 mg/L arsenic exposure groups. The real-time fluorescence quantitative PCR detection results showed that there was a statistically significant difference in the mRNA expression levels of NLGN1, NR2A, and PSD95 in the hippocampal tissues of the four groups ( F = 13.85, 44.94, 4.63, P < 0.05). The results of Western blot analysis showed that the protein expression levels of NLGN1 and NR2A in the hippocampal tissues of rats in the 10 and 50 mg/L arsenic exposure groups were lower than those in the control group (0.65 ± 0.07, 0.69 ± 0.03 vs 1.00 ± 0.04, 0.51 ± 0.11, 0.51 ± 0.13 vs 1.00 ± 0.07, P < 0.05), and the expression level of PSD95 in the hippocampal tissues of rats in the 50 mg/L arsenic exposure group was lower than that in the control group (0.51 ± 0.09 vs 1.00 ± 0.05, P < 0.05). Conclusion:Arsenic may affect synaptic function and cause neurological dysfunction in rats by adjusting the expression levels of NLGN1, NR2A, and PSD95.

Objective:To study the effects of arsenic exposure on neurological function including voluntary motor ability, anxiety, and short-term memory ability of rats, as well as its impact on the expression levels of synaptic function related genes such as neuropeptide 1 (NLGN1), glutamate receptor 2A (NR2A), and postsynaptic density protein 95 (PSD95).Methods:Forty 3-week-old male specific pathogen free (SPF) grade Wistar rats [weighing (453.97 ± 35.68) g] were selected and divided into four groups using a random number table: 0 (control group) and 2, 10, and 50 mg/L arsenic exposure groups, with 10 rats in each group. They were given deionized water and 2, 10, and 50 mg/L sodium arsenite solutions for 12 weeks, respectively. The open field experiment and Y-maze experiment were used to test the voluntary motor ability, anxiety, and short-term memory ability of rats. Nissl staining was used to observe the pathological damage of the hippocampus in the brain. Real time fluorescence quantitative PCR and Western blot were used to detect the mRNA and protein expression levels of NLGN1, NR2A, and PSD95 in the hippocampus, respectively.Results:The results of the open field experiment revealed that the horizontal movement distances of rats in the 2 and 10 mg/L arsenic exposure groups were reduced compared to the control group, the movement distances in the central area in the 2, 10, and 50 mg/L arsenic exposure groups were reduced compared to the control group, and the residence time in the central area in the 10 and 50 mg/L arsenic exposure groups was reduced compared to the control group ( P < 0.05). The results of Y-maze experiment showed that the retention time of new arms in rats of the 2 and 10 mg/L arsenic exposure groups was shorter than that in the control group ( P < 0.05). The pathological examination results of Nissl staining showed that the control group had abundant Nissl bodies in hippocampal tissues of the cytoplasm with intact neuronal structures, tightly arranged cells, appearing blue purple in color and clear visible nuclei. However, the number of Nissl bodies decreased, intercellular gaps increased, disordered arrangement increased, cytoplasmic staining was lighter, and nuclear shrinkage phenomenon increased in the hippocampal tissues of rats in the 2, 10 and 50 mg/L arsenic exposure groups. The real-time fluorescence quantitative PCR detection results showed that there was a statistically significant difference in the mRNA expression levels of NLGN1, NR2A, and PSD95 in the hippocampal tissues of the four groups ( F = 13.85, 44.94, 4.63, P < 0.05). The results of Western blot analysis showed that the protein expression levels of NLGN1 and NR2A in the hippocampal tissues of rats in the 10 and 50 mg/L arsenic exposure groups were lower than those in the control group (0.65 ± 0.07, 0.69 ± 0.03 vs 1.00 ± 0.04, 0.51 ± 0.11, 0.51 ± 0.13 vs 1.00 ± 0.07, P < 0.05), and the expression level of PSD95 in the hippocampal tissues of rats in the 50 mg/L arsenic exposure group was lower than that in the control group (0.51 ± 0.09 vs 1.00 ± 0.05, P < 0.05). Conclusion:Arsenic may affect synaptic function and cause neurological dysfunction in rats by adjusting the expression levels of NLGN1, NR2A, and PSD95.

Objective To investigate the correlation between the level of circulating placental growth factor(PLGF)and the severity of preeclampsia(PE),maternal and infant outcomes and placental pathology.Methods A total of 159 PE patients were selected as the study subjects and divided into the PE1 group(62 PE patients with termination of pregnancy<34 weeks)and the PE2 group(97 PE patients with termination of pregnancy≥34 weeks)according to the gestational age of pregnancy termination.A total of 107 non-PE patients who gave birth during the same period were selected as the control group.Patients were divided into two groups according to the gestational age of termination:the non-PE1 group(41 non-PE patients with termination of pregnancy at<34 weeks)and the non-PE2 group(66 non-PE patients with termination of pregnancy at≥34 weeks).General data were collected in each group of pregnant women,including age,body mass index(BMI),admission systolic blood pressure,diastolic blood pressure,24 h urinary protein quantity,gestational times,presence of FGR and fetal embarrassment.General information of newborns during the operation were collected,for example,whether there was fecal contamination of amniotic fluid,neonatal asphyxia,and days of newborn stayed in NICU.PLGF in venous blood of pregnant women was detected on the day of delivery.The placenta was pathologically detected and scored.After delivery,blood gas of umbilical artery was analyzed,and PH(pH),base surplus(BE),lactic acid(LAC)were recorded.Results There were no significant differences in age,gestational times and delivery times between the PE1 group and the PE2 group and the corresponding the non-PE1 group and the non-PE2 group.BMI was higher in the PE1 group and the PE2 group than that in the non-PE1 group and the non-PE2 group.PLGF was lower in the PE1 group and the PE2 group than that in the non-PE1 group and the non-PE2 group,respectively,and PLGF was lower in the PE1 group than that in the PE2 group(P＜0.05).The 24 h urinary protein quantity,systolic blood pressure,diastolic blood pressure and pathological changes of placenta were higher in the PE1 group than those in the PE2 group(P＜0.05).There were no significant differences in fecal staining of amniotic fluid,fetal embarrassed condition and pH value of umbilical artery blood gas during delivery between the PE1 group and the PE2 group.Compared with the PE2 group,the proportion of neonatal asphyxia and FGR,the umbilical artery blood gas LAC were increased,the BE value was decreased,and the time of staying in NICU was prolonged in the PE1 group(P＜0.05).Conclusion The level of circulating PLGF is decreased in patients with preeclampsia.PLGF has certain value in evaluating PE and predicting adverse pregnancy outcome.

Objective:To detect the expression levels of miR-3074-5p and its target gene p27 in the placental tissues of pre-eclampsia (PE) patients, and to preliminarily explore the association of miR-3074-5p/p27 pathway in the pathogenesis of PE. Methods:From September 2017 to March 2018, 16 pregnant women with PE (PE group) and 9 normal pregnant women (control group) were enrolled in Obstetrics Department in the Second Hospital of Tianjin Medical University. The placental expression levels of miR-3074-5p, p27, cyclin D1 (CCND1) and cyclin dependent kinase 2 (CDK2) were determined by quantitative PCR (qPCR), Western blotting and immunohistochemistry (IHC) analyses. The dual-luciferase reporter assay was applied to authenticate the directly targeted effect of miR-3074-5p on expression of p27 mRNA. The expression of p27 in the human extravillous trophoblast cell line HTR-8/SVneo was down-regulated by its specific shRNA, and the effects of down-regulated p27 expression on physiological activities of HTR-8/SVneo cells were detected. Results:Compared with control group, the expression levels of miR-3074-5p ( P=0.034) and CCND1 ( P=0.031) protein in the placenta of PE patients were significantly decreased, whereas the placental p27 ( P=0.010) protein expression was significantly increased in PE group. IHC analysis showed that, the signals of p27 and CCND1 proteins were dominantly detected in syncytiotrophoblast. The results of dual-luciferase reporter assay confirmed that miR-3074-5p could inhibit the expression of p27 by directly bound to the 3'UTR of p27 mRNA. After the p27 expression was down-regulated, the proliferative and invasive activities of HTR-8/SVneo cells were significantly enhanced ( P=0.014, P=0.045). Conclusion:miR-3074-5p might participate in the regulation of physiological activities of extravillous trophoblast cells by its targeted inhibition on p27 expression, and the abnormally decreased miR-3074-5p in trophoblast cells might be associated with the pathogenesis of PE by promoting the expression of p27.

Objective:To detect the expression levels of miR-3074-5p and its target gene p27 in the placental tissues of pre-eclampsia (PE) patients, and to preliminarily explore the association of miR-3074-5p/p27 pathway in the pathogenesis of PE. Methods:From September 2017 to March 2018, 16 pregnant women with PE (PE group) and 9 normal pregnant women (control group) were enrolled in Obstetrics Department in the Second Hospital of Tianjin Medical University. The placental expression levels of miR-3074-5p, p27, cyclin D1 (CCND1) and cyclin dependent kinase 2 (CDK2) were determined by quantitative PCR (qPCR), Western blotting and immunohistochemistry (IHC) analyses. The dual-luciferase reporter assay was applied to authenticate the directly targeted effect of miR-3074-5p on expression of p27 mRNA. The expression of p27 in the human extravillous trophoblast cell line HTR-8/SVneo was down-regulated by its specific shRNA, and the effects of down-regulated p27 expression on physiological activities of HTR-8/SVneo cells were detected. Results:Compared with control group, the expression levels of miR-3074-5p ( P=0.034) and CCND1 ( P=0.031) protein in the placenta of PE patients were significantly decreased, whereas the placental p27 ( P=0.010) protein expression was significantly increased in PE group. IHC analysis showed that, the signals of p27 and CCND1 proteins were dominantly detected in syncytiotrophoblast. The results of dual-luciferase reporter assay confirmed that miR-3074-5p could inhibit the expression of p27 by directly bound to the 3'UTR of p27 mRNA. After the p27 expression was down-regulated, the proliferative and invasive activities of HTR-8/SVneo cells were significantly enhanced ( P=0.014, P=0.045). Conclusion:miR-3074-5p might participate in the regulation of physiological activities of extravillous trophoblast cells by its targeted inhibition on p27 expression, and the abnormally decreased miR-3074-5p in trophoblast cells might be associated with the pathogenesis of PE by promoting the expression of p27.

Objective To detect the influence of rapamycin on the expression of 4 kinds of miRNAs and the effect cell autophagy.To study the relationship of miR-144 and Beclin-1 gene.Methods SKOV-3 cells were treated with 50 ng/mL rapamycin 2 hours and 10 nmol/L 3-methyl adenine 12 hours,the expression of miR-17,miR-20a,miR-144 and miR-155 was detected by RT-qPCR in SKOV-3 cell of different groups,the protein expression of Beclin-1 was detected by Western blot.The targeting effect of miR-144 on Beclin-1 gene was verified by the dual-luciferase reporter assay,Western blot and RT-qPCR.Results The expression of miR-17,miR-144 and miR-155 were in creased compared with NC groups in rapamycin group (P＜0.05);miR-17,miR-20a and miR-144 were down regulated compared with NC group in 3-MA group(P＜0.05);the protein of Beclin-1 was down expression compared with NC group in rapamycin group.miR-144 could suppress Beclin-1 expression by targeting the specific 3'untranslated region sequence of Beclin-1 gene.Conclusions miR-144 can inhibit the autophagy-related gene Beclin-1 expression and regulate the autophagy process in SKOV-3 cells.

Objective To explore the clinicalpathological characteristics of Lynch syndrome associated ovarian cancer.Methods Totally 260 cases ovarian cancer patients were admitted to Tianjin Medical University General Hospital during Jan.2004 and Jan.2011,among which 10 patients( LS group) belonged to Lynch syndrome associated ovarian cancer according to Amsterdam Ⅱ criteria.One hundred ovarian cancer patients without any family cancer history were enrolled randomizely as control group (sporadic group).Results Lynch syndrome associated ovarian cancer accounted for 3.8％ ( 10/260),the incidence rate of ovarian cancer for female family members of Lynch syndrome was 8.7％ ( 10/115 ).Mean age at time of diagnosis in LS group was (46 ±7) years,significantly earlier than that in sporadic group [ (56 ±11 ) years,P ＜ 0.05 ].There was no statistical difference between two groups in histological type or International Federation of Gynecology and Obstetrics ( FIGO ) stage ( P ＞ 0.05 ).Most of the tissue differentiation in LS group were well or moderate differentiated,there was statistical difference between the two groups(9/10 vs.55％,P ＜0.05).The 3-year and 5-year survival rate in LS group were 87.5％ and 52.5％respectively,compared with 55.4％and 22.7％ in sporadic group(all P＜0.05).Conclusion Compared with sporadic ovarian cancer,Lynch syndrome associated ovarian cancer is more likely present as the clinicalpathological characteristics of early age of onset,serous adenocarcinoma,lower grade and better prognosis.