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Increased intestinal barrier permeability, leaky gut, has been reported in patients with autism. However, its contribution to the development of autism has not been determined. We selected dextran sulfate sodium (DSS) to disrupt and metformin to repair the intestinal barrier in BTBR T+tf/J autistic mice to test this hypothesis. DSS treatment resulted in a decreased affinity for social proximity; however, autistic behaviors in mice were improved after the administration of metformin. We found an increased affinity for social proximity/social memory and decreased repetitive and anxiety-related behaviors. The concentration of lipopolysaccharides in blood decreased after the administration of metformin. The expression levels of the key molecules in the toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88)-nuclear factor kappa B (NF-κB) pathway and their downstream inflammatory cytokines in the cerebral cortex were both repressed. Thus, "leaky gut" could be a trigger for the development of autism via activation of the lipopolysaccharide-mediated TLR4-MyD88-NF-κB pathway.
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Mice , Animals , NF-kappa B , Myeloid Differentiation Factor 88/metabolism , Lipopolysaccharides/pharmacology , Toll-Like Receptor 4/metabolism , Autistic Disorder/metabolism , Signal Transduction/physiologyABSTRACT
China and foreign regulators have conducted multiple discussions on how to use Real World Data (RWD) and Real World Evidence (RWE), also published relevant guidelines and framework files. The development and promotion of RWD/RWE application in China is relatively late, and there is a gap of systems and conditions between China and developed countries. This article aims to learn from advantage experiences of other countries and provide some referential ideas for exploring a strategy of RWD/RWE applications suitable for China by analyzing and comparing the current RWD/RWE application-related policies and guidelines in different regions.
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Objective@#To investigate the clinical featuresand related factors of anti-neutrophil cytoplasmic antibody associated vasculitis (AVV) with interstitial lung disease (ILD), and to explore the high-resolution computed tomography (HRCT) of the chest features between different anti-neutrophil cytoplasmic antibody (ANCA) serotypes.@*Methods@#Clinical date of 125 patients diagnosed with AAV by Tianjin Medical University General Hospital from January 1, 2010 to April 30, 2017 were analyzed retrospectively. Clinical manifestations between AAV patients with ILD or those without ILD (NILD) were compared. Patients who were complicated with ILD were divided into myeloperoxidase (MPO)-ANCA positive subset and proteimase (PR3)-ANCA positive subset, and the pulmonary computed tomographic mani-festation was compared among the two subsets. The count data was analyzed by t test, chi-square test/Fisher exact probality. Logistic regression model was applied to analyze the related factors.@*Results@#Of the 125 AAV patients, 86(68.8%) patients were complicated with inter-stitial lung disease, and the mean age of ILD subgroup was higher than that of the NILD subgroup [(66±11) years vs (56±15) years, t=-3.78, P=0.001]. Com-pared with NILD patients, ILD patients had more symptoms (χ2=4.676, P=0.031). The serum levels of carcinoe-mbryonic antigen (t=-1.908, P=0.012), carbohydrate antigen 19-9 (t=-2.286, P=0.025) and carbohydrate antigen 153 (t=-2.857, P=0.007) were higher than the NILD pa-tients. In addition, MPO-ANCA positivesubgroup was more likely to present with pulmonary fibrosis (χ2=7.736, P=0.005), reticular shadow (χ2=9.762, P=0.002) and honeycombing (χ2=4.278, P=0.039) than PR3-ANCA positive subgroup on CT images of all ILD patients. Multivariate Logistic regressive analysis showed that patients who were older than 65 years [OR(95%CI): 3.305(1.280, 8.531), P=0.013], and Birmin-gham vasculitis activity(BVAS) score higher than or equal to 15 [OR(95%CI): 3.249(1.280, 8.247), P=0.013] were risk factors for AAV patients with ILD, while the probability of PR3-ANCA positive patients complicated with ILD was low [OR(95%CI): 0.063(0.005, 0.851), P=0.037].@*Conclusion@#ILD is a very common clinical feature in AAV, especially for elders. The increase of serum CEA, CA199 and CA153 levels may be an early warning sign of interstitial lung disease. Pulmonary HRCT may more likely to present with pulmonary fibrosis in patients with MPO-ANCA positive.
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Objective To investigate the clinical featuresand related factors of anti-neutrophil cytoplasmic antibody associated vasculitis (AVV) with interstitial lung disease (ILD),and to explore the highresolution computed tomography (HRCT) of the chest features between different anti-neutrophil cytoplasmic antibody (ANCA) serotypes.Methods Clinical date of 125 patients diagnosed with AAV by Tianjin Medical University General Hospital from January 1,2010 to April 30,2017 were analyzed retrospectively.Clinical manifestations between AAV patients with ILD or those without ILD (NILD) were compared.Patients who were complicated with ILD were divided into myeloperoxidase (MPO)-ANCA positive subset and proteimase (PR3)-ANCA positive subset,and the pulmonary computed tomographic mani-festation was compared among the two subsets.The count data was analyzed by t test,chi-square test/Fisher exact probality.Logistic regression model was applied to analyze the related factors.Results Of the 125 AAV patients,86 (68.8％) patients were complicated with inter-stitial lung disease,and the mean age of ILD subgroup was higher than that of the NILD subgroup [(66±11) years vs (56±15) years,t=-3.78,P=0.001].Com-pared with NILD patients,ILD patients had more symptoms (x2=4.676,P=0.031).The serum levels of carcinoe-mbryonic antigen (t=-1.908,P=0.012),carbohydrate antigen 19-9 (t=-2.286,P=0.025) and carbohydrate antigen 153 (t=-2.857,P=0.007) were higher than the NILD pa-tients.In addition,MPO-ANCA positivesubgroup was more likely to present with pulmonary fibrosis (x2=7.736,P=0.005),reticular shadow (x2=9.762,P=0.002) and honeycombing (x~=4.278,P=0.039)than PR3-ANCA positive subgroup on CT images of all ILD patients.Multivariate Logistic regressive analysis showed that patients who were older than 65 years [OR(95％CI):3.305(1.280,8.531),P=0.013],and Birmingham vasculitis activity(BVAS) score higher than or equal to 15 [OR(95％CI):3.249(1.280,8.247),P=0.013] were risk factors for AAV patients with ILD,while the probability of PR3-ANCA positive patients complicated with ILD was low [OR (95％CI):0.063 (0.005,0.851),P=0.037].Conclusion ILD is a very common clinical feature in AAV,especially for elders.The increase of serum CEA,CA199 and CA153 levels may be an early warning sign of interstitial lung disease.Pulmonary HRCT may more likely to present with pulmonary fibrosis in patients with MPO-ANCA positive.
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Objective To compare the clinical effects and influence on CA125,endometrial antibody of trip-torelin the treatment of endometriosis surgery endometriosis surgery,to provide reference for clinical treatment. Methods 60 patients with endometriosis surgery were randomly divided into 30 cases of I group and 30 cases of II group,I group was treated with mifepristone on the first days after menstruation 12.5mg/d,qd,II group was given triptorelin 3.75mg,every 28 days for 1 times,treated for 3 months,the symptoms and signs before and after treatment were observed,then menstruation and dysmenorrhea score were evaluated,Elbow vein blood was taken out for calculat-ing CA125 and serum antiendometrial antibody,the clinical efficacy were evaluated and the adverse reactions were observed,all patients were followed up for 1 years,then 1 years cumulative pregnancy rate were recorded.Results The CA125,EMab,menstrual score,dysmenorrhea score of I group and II group after the treatment were (18.2 ±2.8)U /mL and (8.8 ±3.2)U /mL,(405.2 ±141.1)pg/mL and (202.1 ±79.8)pg/mL,(18.85 ±6.32)score and (7.68 ± 4.19)score,(1.91 ±0.35)score and (0.95 ±0.63)score,all index of both group after treatment were significantly lower than those before treatment(t =8.433 and 14.824,7.659 and 14.578,20.772 and 26.286,15.853 and 19.513,P 0.05);the irregular vaginal bleeding rate of I group was 23.33%,the II group were 3.33%,χ2 =5.192,P <0.05.Conclusion Triptorelin and mifepristone has same clinical effect in endometriosis postoperative,but triptorelin can reduce more effectively the CA125 and anti endometrium antibody,abnormal vaginal bleeding and reduce dysmen-orrhea postoperative,postoperative recurrence rate and pregnancy rate is good,can be used as a recommended drugs in the treatment patients with endometriosis surgery.
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Objective To analyze the clinical value of sTNFR-1,sIL-2Ra and IGF-1 on depression in patients with esophageal cancer by comprehensive nursing intervention and explore the possibility of serum indicators to replace DSI and HAMD. Methods 120 patients with pathologically confirmed esophageal cancer were included in the study.Zung depression status inventory (DSI)and hamilton depression rating scale (HAMD)were used to assess depression.Serum sTNFR-1,sIL-2Ra and IGF-1were detected by enzyme-linked immunosorbent assay (ELISA).Results 69 patients were classified as anxiety and depression group,51 patients were as normal control group.There were 32 patients with depression.Serum sTNFR-1, sIL-2Ra and IGF-1 levels in study group was higher than that in the control group (P<0.05)and these serological indexs increased from the minimal depression,mild-to-moderate depression group to severe depression group (P<0.05).Conclusion Serum sTNFR-1,sIL-2Ra and IGF-1 levels may be used as evaluation index of nursing intervention,but need further clini-cal validation.