OBJECTIVE To investigate the intervention effect and potential mechanism of breviscapine on hepatic fibrosis （HF） in rats based on the transforming growth factor-β（1 TGF-β1）/Smad2/extracellular signal-regulated protein kinase 1（ERK1） and Kelch-like epichlorohydrin-associated protein 1（Keap1）/nuclear factor-erythroid 2-related factor 2（Nrf2）/heme oxygenase-1（HO-1） pathways. METHODS Totally 60 rats were randomly divided into normal control group， model group， breviscapine low-dose， medium-dose and high-dose groups （5.4， 10.8， 21.6 mg/kg）， and colchicine group （positive control， 0.45 mg/kg）， with 10 rats in each group， half male and half female. Except for the normal control group， HF model of the other groups was induced by carbon tetrachloride. Subsequently， each drug group was given corresponding medicine by gavage once a day for 28 days. The liver appearance of rats in each group was observed and their liver coefficients were calculated. The levels of alanineaminotransferase （ALT） and aspartate aminotransferase （AST）in serum， those of ALT， AST， superoxide dismutase （SOD），malondialdehyde （MDA） and glutathione peroxidase （GSH- Px） in liver tissue were detected. The liver tissue inflammatory and fibrotic changes were observed. The protein and mRNA expressions of TGF-β1， Smad2， ERK1， Nrf2， Keap1 and HO-in liver tissue were detected. RESULTS Compared with the normal control group， the model group showed large areas of white nodular lesions in the liver， obvious inflammatory cell infiltration and collagen fiber deposition. The body weight， the levels of SOD and GSH-Px in liver tissue， the protein and mRNA expressions of Nrf2 and HO-1 were significantly lowered in the model group （P＜0.05）； the liver coefficient， the percentage of Masson staining positive area， ALT and AST levels of serum and liver tissue， MDA level of liver tissue， the protein and mRNA expressions of TGF-β1， Smad2， ERK1 and Keap1 were significantly increased （P＜0.05）. Compared with the model group， the liver lesions of rats in each drug group were improved， and the above quantitative indexes were generally reversed （P＜0.05）. CONCLUSIONS Breviscapine has a good intervention effect on HF rats， which may be related to inhibiting TGF-β1/Smad2/ERK1 pathway for anti-fibrosis and regulating Keap1/Nrf2/HO-1 pathway to inhibit oxidative stress.

OBJECTIVE：To explo re the potential molecular mechanism of ursolic acid in the treatment of osteoporosis （OP）. METHODS：TCMSP，PubMed database and UniProt database were used to screen potential targets of monomer compound ursolic acid. OP related target genes were searched with GeneCards database. The common target genes of component-disease were obtained by Venny 2.1 online mapping tool. The protein-protein interaction （PPI）network of component-disease common target genes was constructed by using STRING database ，and topological analysis was carried out ；the core target genes ，whose degree value was greater than the average degree value ，were screened. GO functional annotation and KEGG pathway enrichment analysis of component-disease common target genes were carried out by DAVID database. AutoDock Vina 1.1.2 software was used for molecular docking ，using protein encoded by the core target gene as receptor and ursolic acid as ligand. RESULTS ：A total of 55 ursolic acid related target genes and 4 273 OP related target genes were excavated ，with a total of 44 common target genes. PPI network with above common target genes included 44 nodes and 513 edges，with an average node degree of 23.3. There were 24 core target genes ，including VEGFA，TP53，IL6，CASP3. There were 340 GO functional items were enriched （corrected P＜ 0.05），including 263 biological processes （negative regulation of apoptosis ，etc.），25 molecular functions （protein binding ，etc.） and 52 cell components （cytosol，etc.）. There were 90 KEGG signaling pathways （corrected P＜0.05），such as tumor pathway ， hepatitis B pathway ，TNF signaling pathway ，viral carcinogenesis and phosphatidylinositol 3 kinase/protein kinase B （PI3K-Akt） signaling pathway. The binding energy between ursolic acid and 6 proteins encoded by core target genes such as TP53 was lower than －5 kcal/mol，which had strong binding activity. CONCLUSIONS ：The therapeutic effect of ursolic acid on OP may be achieved by regulating VEGFA，TP53，IL6，CASP3，JUN and other core target genes and acting on multiple key pathways such as cancer pathway ， hepatitis B and TNF signaling

Objective:To search for circulating complement-related proteins that predict hypertensive disorders of pregnancy (HDP) based on reports of the development of gestational hypertension and proteinuria and to investigate the role of the complement system in the development of HDP.Methods:A nested case-control study was used, the serum samples of pregnant women who had been given birth or cesarean section in Guangzhou Women and Children′s Medical Center from November 2014 to March 2017 were collected. A total of 60 HDP and 60 normal pregnant women were included and matched 1∶1 by age and gestational week. Unlabeled mass spectrometry was used to screen the differential expression of complement factors in serum samples of 12 pairs of HDP patients and normal pregnancy collected before 20 weeks of pregnancy, and another 48 pairs of serum samples of HDP patients and normal pregnant women were used for preliminary verification. It was selected when the fold change (FC) of complement factor expression was>1.2 or <0.8 and P<0.05. ROC curve was used to evaluate the diagnostic value of corresponding factors. Results:FC of serum C1s, C8 beta chain (C8β) and C1 inhibitor (C1-INH) of HDP patients were 1.19, 1.23, 0.73 ( t=2.07, 2.06, -3.40; P<0.05), respectively. FC of serum C1s, C8 β, C1-INH, factor H-related protein 5 (CFHR5), clusterin (CLU), and C-reactive protein (CRP) of PE patients were 1.39, 1.50, 0.72, 2.49,4.38, and 1.82 respectively ( t=4.36, 5.61, -3.70, 6.82, 8.70, 7.27; P<0.05).The AUC of combining C1s, C8 β and C1-INH was 0.89 in HDP. The AUC of CFHR5, CLU, and CRP in preeclampsia was 0.88, 0.92, and 0.91. Conclusions:Before HDP, the activation and regulation of classic complement pathway and alternative pathway were disordered in pregnant women. The combined detection of complement C1s, C8 β and C1-INH is expected to be used in the prediction of HDP, and CFHR5, CLU, and CRP are expected to be used in the prediction of preeclampsia.

Objective Find abnormal changes of plasma lipid metabolism-related proteins before 20 weeks of gestation in patients with hypertensive disorder of pregnancy(HDP), and preliminarily investigate the role of plasma apolipoprotein C4 elevation in HDP. Methods A nested case-control study was used. The plasma were collected from pregnant women who underwent routine prenatal examination in Guangzhou Women and Children's Medical Center from November 2014 to March 2017. Label-free mass spectrometry was used to detect the differences in plasma lipid metabolism-related proteins before 20 weeks of gestation between 12 pairs of HDP patients and normal controls, and different 48 pairs of samples were used for verification. The protein with the most significant difference multiples was screened to study its effects on monolayer permeability and nitric oxide secretion of endothelial cells. One-way ANOVA was used for comparison between groups, and P<0.05 was considered as statistically significant difference. Results Compared with the control, the lipid metabolism-related proteins, APOC4, Fatty acid-binding protein 4 (FABP4), Apolipoprotein E (APOE), Apolipoprotein C3 (APOC3) and Beta-2-glycoprotein 1(APOH) raised to 1.94, 1.82, 1.59, 1.55 and 1.38 times, phospholipid transfer protein (PLTP) decreased to 0.78 times in plasma before 20 weeks of pregnancy of patients with HDP (t value were 2.499, 2.497, 2.081, 2.098, 2.426 and 2.564, respectively, P<0.05). Cell experiments results showed that 50 ng / ml APOC4 significantly increased 20％ HUVEC single layer cell permeability to FITC-labeled dextran (F=455.4, P<0.01), and significantly decreased the level of nitric oxide in the supernatant of HUVEC culture by 25％ (F=61.92, P<0.01). Conclusions Before diagnosis, plasma protein levels involved in lipid metabolism in HDP patients have been changed, resulting in abnormal lipid metabolism. APOC4 can increase the permeability of vascular endothelial cells, inhibit endothelial source of NO secretion, cause endothelial dysfunction.

BACKGROUND: Exposure to organic dust has been widely investigated as a potential risk factor for asthma with different results. To clarify a potential relationship, we performed the present meta-analysis to integrate the results of studies examining the association of organic dust exposure with asthma. METHODS: A comprehensive literature search in the electronic databases including EMBASE, PubMed and Cochrane Library databases (up to August 2018) was conducted. The adjusted odds ratios (ORs) with corresponding 95% confidence interval (CI) for organic dust exposure and asthma were retrieved and pooled to generate summary effect estimates in Revman 5.2. RESULTS: Database searches retrieved 1,016 records. A total of 17 studies containing 3,619 cases and 6,585 controls were finally included in our meta-analysis. The summary estimates suggested that organic dust exposure was positively associated with asthma (OR, 1.48; 95% CI, 1.26–1.75; P < 0.00001), whether among population-based case-control studies (OR, 1.24; 95% CI, 1.13–1.35; P < 0.00001) or hospital-based case-control studies (OR, 2.79; 95% CI, 1.27–6.12; P = 0.01). Subgroup analysis showed that paper/wood (OR, 1.62; 95% CI, 1.38–1.90; P < 0.00001), flour/grain (OR, 1.48; 95% CI, 1.11–1.97; P = 0.008), and textile dust (OR, 1.50; 95% CI, 1.08–2.09; P = 0.02) exposure were significantly associated with asthma. CONCLUSIONS: Based on the studies evaluated, our meta-analysis results prompt that organic dust exposure is a risk factor inducing asthma, although precise analysis focus on specific organic dust materials is still warranted.
Asthma ; Case-Control Studies ; Dust ; Odds Ratio ; Risk Factors ; Textiles

As a promising candidate seed cell type in regenerative medicine, mesenchymal stem cells (MSCs) have attracted considerable attention. The unique capacity of MSCs to exert a regulatory effect on immunity in an autologous/allergenic manner makes them an attractive therapeutic cell type for immune disorders. In this review, we discussed the current knowledge of and advances in MSCs, including its basic biological properties, i.e., multilineage differentiation, secretome, and immunomodulation. Specifically, on the basis of our previous work, we proposed three new concepts of MSCs, i.e., "subtotipotent stem cell" hypothesis, MSC system, and "Yin and Yang" balance of MSC regulation, which may bring new insights into our understanding of MSCs. Furthermore, we analyzed data from the Clinical Trials database ( http://clinicaltrials.gov ) on registered clinical trials using MSCs to treat a variety of immune diseases, such as graft-versus-host disease, systemic lupus erythematosus, and multiple sclerosis. In addition, we highlighted MSC clinical trials in China and discussed the challenges and future directions in the field of MSC clinical application.
Cell Differentiation ; Humans ; Immune System Diseases ; immunology ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells ; immunology ; physiology ; Randomized Controlled Trials as Topic ; Regenerative Medicine

Objective To evaluate the technical success rate,effectiveness and safety of transcatheter arterial chemoembolization (TACE)via the omental branch in the treatment of hepatocellular carcinoma (HCC)with blood supply from the omental branch. Methods 45 patients with HCC fed by the omental branch who had undergone TACE were evaluated retrospectively.Results All patients had undergone several therapeutic procedures including TACE before the revelation of the blood supply from the omental branch,8 patients had a history of surgery of hepatic resection for HCC.45 patients had 48 tumors total,52 omental branches were observed angiographically,48 omental branches (9 2%)were successfully embolized.Stenosis or occlusion of the hepatic artery was observed in 37 patients(82%).The alpha fetoprotein (AFP)levels were reduced from 5.05－4 246.89 ng/mL(mean,1 748.52 ng/mL)before treatment to 3.78－1 048.32 ng/mL(mean,287.46 ng/mL)after TACE 4－6 weeks later.The tumors diminished in size in 32 patients,stabilized in 13 patients(29%),however,recurred 2－6 months (mean,3 months)after TACE.28 patients died after 6－18 months (mean,10 months),17 patients were alive for 3－32 months (mean,14 months),but tumor recurred in 8 patients.Severe complications were not observed in any patient.Conclusion TACE via the omental branch is safe,effective and had high technical success rate,it is important to embolize all the feeding arteries at the same time for reducing the recurrence rate.

Objective To investigate the effect of propofol on the secretory function of adrenal medullary chromaffin cells of rats.Methods The rat adrenal pheochromocytoma cells cultured in vitro were seeded in 24-well plates at a density of 1×1010 cells/ml and divided into 5 groups (n=12 each) using a random number table:control group (group C),different concentrations of propofol groups (P1 and P2 groups),and different concentrations of etomidate groups (E1 and E2 groups).Propofol was added with the final concentrations of 30 and 100 μmol/L in P1 and P2 groups,respectively.Etomidate was added with the final concentrations of 4 and 40 μmol/L in EI and E2 groups,respectively.The cells were then incubated for 10 min in an incubator at 37 ℃.At the end of incubation with drugs,6 wells in each group were selected,and physiological salt solution 200 μl was added;another 6 wells in each group were selected,and high K+ physiological salt solution was added.[3 H] PSS and [3 H] K+-PSS were measured by [3 H] norepinephrine release assays.Results Compared with group C,[3 H] K+-PSS and [3 H] K+-PSS/PSS were significantly decreased in P1,P2 and E2 groups (P＜0.05),and no significant changes were found in [3H] K+-PSS and [3H] K+-PSS/PSS in group E1 (P＞0.05).Compared with group P1,[3 H] K+-PSS and [3 H] K+-PSS/ PSS were significantly decreased in group P2 (P＜0.05).Conclusion Propofol can inhibit the secretory function of adrenal medullary chromaffin cells of rats in a concentration-dependent manner.

Aim To investigate the induction effect of ginsenoside Rc, Re, Rf and Rg1 on CYP1A1, and further validate the role of aryl hydrocarbon receptor in CYP1A1 expression. Methods Dual luciferase re-porter gene system was performed. Four kinds of gin-senoside were screened for aryl hydrocarbon receptor activation by reporter assays, and TCDD as the positive control. Further with different concentrations of ginsen-oside Rc, Re, Rf and Rg1 treated on LS174T cells, RNA and total protein were extracted to detect the reg-ulating effect of ginsenosides on CYP1 A1 mRNA and protein expression with Real-time PCR and Western blot technology respectively. Results Reporter gene screening showed that the ginsenoside Rc, Re, Rf and Rg1 could activate AhR and had potential effects on the induction of CYP1A1 enzyme. Meanwhile, dose-de-pendent induction of the gene expression were observed in response to ginsenoside Rc, Re, Rf and Rg1 and the levels of CYP1 A1 protein expression were increased by ginsenoside Rc, Re, Rf and Rg1 in varying de-grees. Conclusion Ginsenoside Rc, Re, Rf and Rg1 can up-regulate the gene and protein expression of CYP1 A1 possibly via the AhR-mediated CYP1 A1 path-way.

Objective To explore the relationship between the size of the kidney and gender,age,height,weight,waist circumference then derive an estimation formula of a normal kidney size for different people.Methods We investigated 1 000 normal cases who accepted the examination in Tianjin Medical University General Hospital from December 2011 to April 2012,including 462 males,538 females,aged 21-78 years.All the investigated subjects were healthy except for hypertension,diabetes,coronary heart disease.Blood urea nitrogen (BUN) and creatinine (Cr),fasting glucose,uric acid,routine urine test were all in the normal range.Height,weight,and waist circumference were measured for all the subjects.The renal length and transverse diameter in supine coronal sections,anteroposterior diameter in vertical cross-section of the renal hilum were measured by the same technical experts with Philip iU22 C5-1,3.5 MHz convex array probe.Results The right and left kidney size both are significantly related to height (right r=0.845,left r=0.876,P＜0.01).By multiple regression analysis,there was a significant association between height,weight,body surface area and kidney size (R2＞0.5).Linear regression formula for the kidney length and the height(H,cm):Kidney length of men:right 0.059×H+0.144; left:0.061 ×H+0.287.Kidney length of women:right 0.039×H+3.679; left:0.035×H+4.454.Regardless of gender,the formula of left kidney length:0.052× H+0.721.Linear regression formula about the left kidney length and the height,body weight and body surface area (unit:H cm,W kg,BSA m2):0.114×H+0.139×W-10.287×BSA+2.112.Conclusion There is the best correlation between kidney length and height.Height,weight,body surface area have great influence on kidney size.