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Background Permethrin is a commonly used pyrethroid insecticide and has been found to be potentially neurotoxic. Microglia are innate immune cells in the central nervous system and are involved in the development of a range of neurodegenerative diseases. Objective To observe possible toxic effects of permethrin on human microglia clone 3 (HMC3) in vitro and explore associated mechanism. Methods HMC3 were treated with 0, 10, 25, and 55 μmol·L−1 permethrin for 72 h. Cell cycle and apoptosis were measured using flow cytometry. Cyclin-dependent kinase 1 (CDK1), cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin B2 (CCNB2), cellular tumor antigen p53 (p53), factor-related apoptosis (FAS), caspase 3 (CASP3), and H2A histone family member X (H2AX) were detected by quantitative real-time PCR (qPCR). The differential genes and enrichment pathways of HMC3 after 0 and 25 μmol·L−1 permethrin treatment was analyzed by RNA sequencing. HMC3 was treated by 0, 10, 25, and 55 μmol· L−1 permethrin for 72 h. The content of nitric oxide (NO) in the supernatant was detected using Griess reagent. The secretion level of interleukin-6 (IL-6) was detected by enzyme linked immunosorbent assay (ELISA). The mRNA expression levels of mitogen-activated protein kinase (MAPK) pathway (including MAPK1, MAPK8, and MAPK14), interleukin-1β (IL-1β), IL-6, and matrix metalloproteinase (MMP) families (including MMP1, MMP2, MMP3, and MMP9) were detected by qPCR. The protein expressions of phosphorylated p38 mitogen-activated protein kinase (p-p38), phosphorylated extracellular signal-regulated kinase (p-ERK), IL-1β, IL-6, and MMP1 were detected by Western blot. Results HMC3 was arrested in G2/M phase after 0, 10, 25, and 55 μmol·L−1 permethrin treatment for 72 h, of which there was a statistically significant difference between the 55 μmol·L−1 permethrin treatment group and the control group (P<0.01), and the mRNA expression of CDKN1A was up-regulated according to the qPCR (P<0.05). There was no statistically significant difference in the proportions of apoptosis between the groups (P＞0.05). The RNA sequencing showed that the differential genes were enriched in the MAPK pathway, and the mRNA expressions of MAPK1, MAPK8, and MAPK14 were up-regulated after the permethrin treatment at 55 μmol·L−1 compared to the control group by qPCR (P<0.05). The Western blot revealed that, compared to the control group, the levels of p-p38 and p-ERK were increased after the 10 μmol·L−1 permetrin treatment (P<0.05), the p-ERK level was increased after the 25 μmol·L−1 permetrin treatment (P<0.05), and the p-p38 level was up-regulated after the 55 μmol·L−1 permetrin treatment (P<0.05). The secretion of NO in the supernatant of HMC3 increased after permetrin treatment compared to the control group (P<0.05), the mRNA and protein expressions and the secretion of IL-6 showed an upward trend, the mRNA and protein expressions of IL-1β were up-regulated (P<0.05), and the mRNA and protein expressions of MMP1 were up-regulated in the 25 and 55 μmol·L−1 permethrin groups (P<0.05). Conclusion Permethrin inhibits HMC3 cell proliferation in vitro, induces cell cycle arrest, activates MAPK pathway, and promotes the expression of inflammatory factors IL-1β and MMP1, which may be one of the mechanism of neurotoxicity induced by permethrin.
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Objective:To investigate the effect of Duhuo Jisheng Decoction on early cartilage destruction markers in patients with rheumatoid arthritis with kidney-qi deficiency and cold syndrome.Methods:A total of 64 patients with rheumatoid arthritis in our hospital from March 2019 to March 2020 who met the inclusion criteria were divided into 2 groups, according to the random number table method, with 32 in each group. The control group was given conventional western medicine therapy, and the observation group was given Duhuo Jisheng decoction on the basis of the control group. Both groups were treated for 8 weeks. TCM syndrome scores were performed before and after treatment, serum CRP, IL-6, cartilage oligosaccharide protein (COMP) and β-catenin were detected by ELISA method, and adverse eventns during treatment were observed and compared. The clinical efficacy was evaluated.Results:The total effective rate was 87.5% (28/32) in the observation group and 65.6% (21/32) in the control group, and the difference between the two groups was statistically significant ( χ2=4.27, P=0.039). After treatment, the main symptoms, secondary symptoms and tongue and pulse scores of the observation group were significantly lower than those in the control group ( t=7.11, 3.11, 2.41, P<0.01 or P<0.05); serum CRP and IL-6 levels were significantly lower than those in the control group ( t=3.04, 4.56, P<0.01); serum COMP [(12.37±1.68) μg/L vs. (14.24±1.88) μg/L, t=4.20], β-catenin [(1.35±0.24) μg/L vs. (1.68±0.31) μg/L, t=4.76] levels were significantly lower than those in the control group ( P<0.01). During the treatment, the incidence of adverse events was 25.0% (8/32) in the observation group and 18.8% (6/32) in the control group, and there was no significant difference between the two groups ( χ2=0.37, P=0.546). Conclusion:The Duhuo Jisheng Decoction can help to reduce the levels of inflammatory cytokines and early cartilage destruction markers in patients with rheumatoid arthritis, and improve the clinical efficacy safely.
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Objective DNA methylation in the pathogenesis of endometriosis is drawing more and more attention from the medical world.This study aimed to evaluate the methylation status of the Homeobox-A10 (HOXA10) gene promoter region and the expression of the HOXA10 protein in endometriosis,and to explore the relationship of endometriosis with the aberrant methylation and expression of HOXA10 and its clinical significance.Methods The methylation-specific PCR(MSP) and the immunohistochemical SP methods were employed to detect both the methylation status of the HOXA10 promoter and its expression in the eutopic and ectopic endometrial tissues from 36 endometriosis patients,with normal endometrial tissue samples from 12 healthy women as controls.Results Hypermethylation of the HOXA10 promoter region was present in 38.9% (14/36) of the ectopic endometrial tissue samples and 25.0% (9/36) of the eutopic endometrial tissue samples,all in endometriosis of stages Ⅲ and Ⅳ,but no hypermethylation was found in the endometrial tissues of the normal controls,with significant differences between the two groups (P
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Objective:To evaluate the efficacy and safety of controlled-release dinoprostone pessary(propess) in cervical ripening and intermediate labor induction.Methods:Eighty primiparas with uterogestation and Bishop score ≤6 points and no vaginal delivery taboo were equally divided into a study and a control group.The former received intravaginal administration of propess and the latter intravenous injection of low-dose oxytocin by the randomized control method.Comparisons were made of the Bishop score,delivery and the state of the fetuses and neonates between the two groups.The side effects of propess were observed.Results:Bishop scores were 7.75?2.227 and 6.38?2.862 in the study and the control group respectively 12 hours after the medication,significantly higher than 4.23?1.025 and 4.15?1.099 before the induction(P 0.05).The major side effect of propess was the over-frequent and over-strong contraction of the uterine,which occurred in 2 cases in the study group but subsided after its removal.Conclusion:Dinoprostone pessary,effective,safe and convenient,is obviously superior to oxytocin in cervical ripening and labor induction.
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Objectives:To investigate the level of soluble intracellular adhesion molecule 1 (sICAM 1) concentrations in the serum and peritoneal fluid from the patients with or without endometriosis.To discuss the relationship within sICAM 1 and pelvic endometriosis. Methods:35 serum and 30 peritoneal fluid of patients with endometriosis (test group) and 26 serum and 4 peritoneal fluid without endometriosis (control group) were studied.Soluble intracellular adhesion molecule 1 levels were detected by an enzyme linked immunoassay(ELISA).The results were analysed by T test. Results: The serum concentration of sICAM 1 was significantly higher in test group than controll group. However,There was no significant difference in between two groups. Conclusions: These results suggest that sICAM 1 could play some role in the persistence of endometriotic lesions.
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Objective: To investigate a moderate dose of levobupivacaine in spinal anesthesia for caesarean section.Methods: Eighty parturients undergoing caesarean section were randomly divided into 4 groups: GroupⅠ(0.75% levobupivacaine 1.00ml+10% glucose 1.00ml+cerebrospinal fluid 1.00ml),GroupⅡ(0.75% levobupivacaine 1.33ml+10% glucose 1.00ml+ cerebrospinal fluid 0.67ml),Group Ⅲ(0.75% levobupivacaine 1.67ml+10% glucose 1.00ml+ cerebrospinal fluid 0.33ml) and Group Ⅳ(0.75% levobupivacaine 2.00ml+10% glucose 1.00ml).The spinal puncture sites were all located at L_2,3.The onset time of sensation block,the highest plane of analgesia,the time to reach the highest plane of analgesia,the time of regression to the L_1 segment,the degree of motor block,VAS scores,the degree of muscle relaxation,the rate of hypotension incidents and neonatal Apgar scores were recorded. Results: There were no statistically significant differences in the onset time of sensation block,the time to reach the highest plane of analgesia and the highest plane of analgesia among the 4 groups.But the durations of regression to the L_1 segment were dramatically shorter in GroupⅠand Ⅱthan in Group Ⅲ and Ⅳ(P
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Objectives:To study the clinicopathological features of extraovarian peritoneal serous papillary carcinoma.Methods:The clinical pictures and pathological characteristics of 6 cases extraovarian peritoneal serous papillary carcinoma admitted to our hospital from 1992 to 1999 were studies retrospectively.H & E staining,histochemical staining and immunohistochemical staining were used.Results:The ages of the 6 patients were between 32～62(43.7) years old.The bilateral ovaries and fallopian tubes were almost normal.Tumors were examined histomorphologically by microscope and electron microscope,periodic acid-Schiff (PAS) stain was used in the histochemical study and carcinoembryonic antigen (CEA),CA125,p53,AE1 and AE3 monoclonal antibody assays were detected immunohistochemically.The results revealed no difference between extraovarian peritoneal serous papillary carcinoma and ovarian serous papillary carcinoma.Conclusions:Extraovarian peritoneal serous papillary carcinoma is considered arising from the secondary Müllerian system.Histologically,extraovarian peritoneal serous papillary carcinoma was identical to that of the similar epithelial carcinomas arising from the ovaries.The diagnosis was made only when the ovaries were not involved and without any evidence of similar epithelial carcinoma obtained in the ovaries.Histochemical staining and immunohistochemical staining are helpful as accessory criteria for the differential diagnosis between primary carcinoma of the peritoneum and malignant mesothelioma.The prognosis is poor.