Objective To investigate whether gastroesophageal reflux can cause asthma-like pathophysiological changes and its mechanism.Methods Sixty BALB/c mice were randomly divided into 4 groups:group A was gastroesophageal reflux control group,group B was asthma control group,group C was gastroesophageal reflux group,and group D was asthmatic group.The asthmatic models were replicated with ovalbumin(OVA) and aluminum hydroxide,and gastroesophageal reflux models were replicated with hydrochloric acid solution pepsin.After the last inhaling ovalbumin and slow perfusion,the airway pressure was detected,and eosinophil (EOS) and neutrophil granulocyte in bronchial lavage fluid were counted.The flow cytometer was used to determinate IL-4,IFN-γ,and Th1/Th2 ratio changes of spleen cells;Lung tissue and esophagus sections were stained with HE,and pathological changes of lung tissue and esophagus were observed.Results In group C and group D,the airway hyper-responsiveness was significantly increased compared with group A and group B,and the differences were statistically significant (all P ＜ 0.05).In group C and group D,IL-4were significantly increased,while IFN-γand Thl/Th2 ratio were significantly decreased than that in the group A and B group,the differences were statistically significant (all P ＜ 0.05).EOS of group C and group D accounted for a high percentage of total cells and they were significantly higher than that in group A and group B,and the differences were statistically significant (all P ＜ 0.05).Through lung tissue biopsy,in group C and group D,bronchial lumen deformation,infiltration of inflammatory cells around the wall,basement membrane thickening,inflammatory cell infiltration around the wall,peripheral vascular edema,enlarging alveolar cavity,alveolar wall thinning,fracture,part of alveolar fusion into bullace of lung,could be observed.The lung pathological section showed that the endothelial cells in group A and group B were integrated and had no denaturation or necrosis,and there was no inflammation cell infiltrate around.EOS biopsy could be observed in group A and group B of lower esophagus markedly submucosal edema,submucosal inflammatory cell infiltration,and keratin hyper function,visible bacteria group A group B and group D were basic ally normal,with no pathological changes.Conclusions Gastroesophageal reflux can induce Th1/Th2 decreasing,airway hyper-responsiveness and pathophysiological changes similar to asthma.

OBJECTIVETo investigate the pathophysiological role of CXCL16 in immunological liver injury induced by Bacille de Calmette et Guerin (BCG) and lipopolysaccharides (LPS).

METHODSImmunological liver injury was induced by BCG and LPS in mice, and the expression of CXCL16 was detected in the liver tissues by real-time quantitative PCR and immunohistochemical examination. The relationship of the expression of CXCL16 and the extent of hepatic necrosis was investigated histopathologically and immunohistochemically. Mononuclear cells were isolated from the liver tissues and their numbers were counted; T lymphocytes populations in the liver tissue were also analyzed with FACS.

RESULTSThe immunological liver injury model was successfully created. Up-regulation of CXCL16 in injured livers correlated with the extent of liver injury and the amountmononuclear cell infiltrations.

CONCLUSIONThese findings suggest that up-regulation of CXCL16 was closely correlated with liver injury extent during the immunological liver injury induced by BCG-LPS in mice, and intrahepatic recruitment of specific lymphocytes might be an important mechanism of liver injury.

Animals ; Chemical and Drug Induced Liver Injury ; Chemokine CXCL16 ; Chemokine CXCL6 ; Chemokines, CXC ; biosynthesis ; genetics ; Lipopolysaccharides ; Liver Diseases ; metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mycobacterium bovis ; Receptors, Scavenger ; biosynthesis ; genetics

Fingerprint technology is the key technology in modern Chinese medicine research, while spectrum-effect relationship research is the advanced stage of fingerprint research. Spectrum-effect relationship research can reveal the relationship between fingerprint and pharmacological effect through multiple statistical analyses, which can be used in Chinese medicine research. Spectrum-effect relationship has been used in many areas of Chinese medicine research, such as effective basis of single and compound Chinese medicine research, component compatibility research, processing mechanism research, pharmacological effect forecast research, technology optimization research, and so on. This paper systematically reviewed the application of spectrum-effect relationship in Chinese medicine research, and indicated some problems in spectrum-effect relationship research. At last, the authors give an outlook of the future of spectrum-effect relationship research.
Animals ; Biomedical Research ; China ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Humans ; Spectrum Analysis

OBJECTIVETo evaluate the correlation of 64-multidetector-row CT (64MDCT) perfusion imaging with microvessel density(MVD) and vascular endothelial growth factor(VEGF) in colorectal carcinoma.

METHODS64MDCT perfusion imaging was performed in 33 patients with pathologically verified colorectal carcinoma. Time-density curves (TDC) were created from the region of interest (ROI) drawn over the tumor, target artery and vein by 64MDCT with perfusion functional software. The individual perfusion maps generated were for blood flow (BF), blood volume (BV), mean transit time (MTT) and permeability-surface area product (PS). MVD and VEGF expression of surgical specimens were examined by immunohistochemical staining with anti-CD34, anti-VEGF monoclonal antibody. MVD and VEGF were compared among the different types of TDC in colorectal carcinoma. The correlation of CT perfusion parameters with MVD and VEGF was also examined.

RESULTSTDC of colorectal carcinoma was divided into five types according to their shapes. MVD in the colorectal carcinoma was 22.61+/-9.01. VEGF staining was found in 25 of 29 tumors (86.2%). The score of VEGF expression was 4.15+/-1.09. No significant differences of MVD and VEGF expression among TDC types were found (F=2.59, 1.11, P>0.05). There were also no correlations of MVD and VEGF expression with any dynamic CT parameters (P>0.05).

CONCLUSION64MDCT perfusion imaging, MVD and VEGF may reflect angiogenic activity, but no significant correlations are found among them.

Adult ; Aged ; Colorectal Neoplasms ; blood supply ; diagnostic imaging ; Female ; Humans ; Male ; Microvessels ; Middle Aged ; Neovascularization, Pathologic ; Tomography, Spiral Computed ; methods ; Vascular Endothelial Growth Factor A ; metabolism ; Young Adult

OBJECTIVETo study the association between the single nucleotide polymorphisms (SNPs) in FXYD6 gene and schizophrenia in a family-trios population.

METHODSSix SNPs (rs10790212, rs11544201, rs555577, rs1815774, rs4938446 and rs497768) in the FXYD6 gene were genotyped by allele-specific PCR method in 101 nuclear families, and transmission disequilibrium test (TDT) was performed.

RESULTSSNPs rs10790212 and rs11544201 showed significant association with schizophrenia (P<0.05). Furthermore, significant association of schizophrenia with the haplotype rs10790212-rs11544201 was found (P<0.05).

CONCLUSIONFXYD6 gene might play an important role in schizophrenia susceptibility and functional analysis of FXYD6 are needed.

Adolescent ; Adult ; Alleles ; Female ; Genetic Predisposition to Disease ; Haplotypes ; Humans ; Ion Channels ; genetics ; Linkage Disequilibrium ; genetics ; Male ; Polymorphism, Single Nucleotide ; genetics ; Schizophrenia ; genetics ; Young Adult

OBJECTIVETo study the effects of high-density lipoprotein (HDL) and oxidized high-density lipoprotein (ox-HDL) on the expression of ATP-binding cassette transporter A1 (ABCAl) and cholesterol efflux in human umbilical vein endothelial cells (HUVECs).

METHODSIn vitro cultured HUVECs were incubated in the presence of 100 microg/ml HDL or 100 microg/ml ox-HDL for 24 h, using PBS as the negative control. ABCA1 mRNA level and cholesterol efflux rate were determined using RT-PCR and a liquid scintillator, respectively.

RESULTSHDL and ox-HDL significantly elevated the level of ABCA1 mRNA by 58% and 23% relative to the control level, respectively (P<0.05). The cholesterol efflux rate in ox-HDL group was significantly lower than that in HDL group (P<0.01).

CONCLUSIONHDL increases ABCAl expression and cholesterol efflux in HUVECs. Oxidative modification of HDL decrease cholesterol efflux by inhibiting the expression of ABCAl, suggesting a possible mechanism of ox-HDL in the pathogenesis of atherosclerosis.

ATP Binding Cassette Transporter 1 ; ATP-Binding Cassette Transporters ; genetics ; metabolism ; Cells, Cultured ; Cholesterol ; metabolism ; Endothelial Cells ; metabolism ; Humans ; Lipoproteins, HDL ; metabolism ; physiology ; Umbilical Veins ; cytology

OBJECTIVESix1 and Six4 are expressed in several tumors, and associated with tumor progress and poor prognosis. The aim of this study was to investigate the expression of Six1 and Six4 in esophageal squamous cell carcinoma (ESCC), and to evaluate their correlation with the clinicopathological factors and prognosis.

METHODSTissue microarray technology and immunohistochemical method (EnVision) were used to detect the expression of Six1 and Six4 in the tumor tissues and corresponding adjacent normal epithelium of esophagus from 292 ESCC patients.

RESULTSAmong the 292 ESCC patients, the positive rates of Six1 and Six4 protein expression in tumor tissues were 72.9% (213/292) and 56.2% (164/292), respectively, significantly higher than the expression rate of 33.2% (97/292) and 32.5% (95/292) in adjacent normal epithelium of esophagus (P < 0.05). Chi square test showed that the expression of Six1 protein was related to tumor size, depth of tumor invasion and patient survival status; higher Six4 protein expression level was related to poor differentiation and increased depth of invasion. Single factor Log-rank analysis revealed that gender, TNM stage, Six1 protein expression level were related to the overall survival of ESCC patients (P < 0.05), while the five-year survival rate was significantly higher in the Six1-negative group than the Six1-positive group [51.9% (41/79) vs. 43.7% (93/213)]. Multi-factor Cox proportional risk model analysis showed that TNM stage and positive expression of Six1 were independent prognostic factors for ESCC patients (P < 0.05).

CONCLUSIONSSix1 and Six4 are highly expressed in ESCC. Their expression levels are closely related to the progress and prognosis of ESCC. Over-expression of Six1 is related to poor prognosis in ESCC patients. Thus, Six1 could be used as an important prognostic indicator for ESCC patients.

Adult ; Aged ; Carcinoma, Squamous Cell ; metabolism ; pathology ; surgery ; Esophageal Neoplasms ; metabolism ; pathology ; surgery ; Female ; Follow-Up Studies ; Homeodomain Proteins ; metabolism ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Risk Factors ; Survival Rate ; Trans-Activators ; metabolism ; Tumor Burden

Aim To evaluate the efficacy of the combination of leonurine(SCM),polygonatum polysaccharide(PSP)and deoxynojirimycin(DNJ)in hypoglycemic and antithrombotic aspects by establishing and using zebrafish type II diabetes combined with thrombosis model. Methods On the basis of the zebrafish type II diabetes model established by streptozotocin,phenylhydrazine(PH),arachidonic acid(AA)and ponatinib(PT)were used respectively to establish thrombosis models,which were divided into control group,model group,metformin+aspirin group,and the high,medium and low concentration groups of the combination drugs. After drug intervention in the experimental group,the thrombosis of tail vein was observed. Kit was used to determine the sugar content of juvenile fish tissues in each group. Quantitative analysis of cardiac erythrocytes by o-dianisidine staining method was used to calculate the inhibition rate of thrombus. Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect the mRNA expressions of related genes in zebrafish. Results Compared with the model group,the combined drug could significantly increase the staining intensity of erythrocytes in zebrafish hearts,inhibit thrombosis,down-regulate the expression of thrombosis-related genes,and reduce tissue glucose content. Conclusions The combined use of the three drugs can effectively reduce the tissue sugar content and have antithrombotic effect,which show great potential in the development of drugs for the treatment of type II diabetes and thrombosis.

In current study, we aimed to investigate whether the gentiopicroside (GPS) derived from Gentiana manshurica Kitagawa could block the progression of alcoholic hepatic steatosis to fibrosis induced by chronic ethanol intake. C57BL/6 mice were fed an ethanol- containing Lieber-DeCarli diet for 4 weeks. LX-2 human hepatic stellate cells were treated with GPS 1 h prior to transforming growth factor-β (TGF-β) stimulation, and murine hepatocyte AML12 cells were pretreated by GPS 1 h prior to ethanol treatment. GPS inhibited the expression of type I collagen (collagen I), α-smooth muscle actin (α-SMA) and tissue inhibitor of metal protease 1 in ethanol-fed mouse livers with mild fibrosis. In addition, the imbalanced lipid metabolism induced by chronic ethanol-feeding was ameliorated by GPS pretreatment, characterized by the modulation of lipid accumulation. Consistently, GPS inhibited the expression of collagen I and α-SMA in LX-2 cells stimulated by TGF-β. Inhibition of lipid synthesis and promotion of oxidation by GPS were also confirmed in ethanol-treated AML12 cells. GPS could prevent hepatic steatosis advancing to the inception of a mild fibrosis caused by chronic alcohol exposure, suggesting GPS might be a promising therapy for targeting the early stage of alcoholic liver disease.

Objective To explore the influencing factors and correlation of positive surgical margin (PSM) and biochemical recurrence (BCR) in men after robot-assisted radical prostatectomy (RALP).Methods The clinical data of 190 patients with local or locally advanced prostate cancer who underwent RALP by single surgeon in the Department of Urology of Changhai Hospital from January 2016 to September 2017 were collected.Age was (67.5 ±6.9) years old;median body mass index (BMI),preoperative PSA,prostate weight were 24.2 kg/m2 (16.6-34.2 kg/m2),15.0 ng/ml (1.41-393.94 ng/ml) and 36.9 g (8.65-207.58 g) respectively.The group of surgical margin was divided into negative surgical margin,apex-only PSM,base-only PSM as well as apex and base PSM.Characteristics between patients stratified by surgical margin or BCR were compared using x2 test.The influencing factors of PSM were analyzed by logistic regression.Cox regression was used for the analysis of predictive factors of BCR.Log-rank test and Kaplan-Meier curves were used for comparing the BCR rate between the groups of surgical margin.Results Of all the 190 enrolled patients,total PSM rate was 24.7％ (47/190),apex-only PSM rate was 13.2 ％ (25/190),base-only PSM rate was 5.8％ (11/190),apex and base PSM rate was 5.8 ％ (11/190).Multivariate analysis showed the independent predictive factors influencing PSM were preoperative PSA (P =0.048) and pathological stage (P =0.004).The median follow-up period was 7.3 months (0.9-26.6months) and BCR happened in 19.5％ (37/190) patients.The rates of BCR were 15.4％ (22/143),16.0％ (4/25),27.3％ (3/11) and 72.7％ (8/11) in the patients with negative surgical margin,apexonly PSM,base-only PSM and both apex and base PSM respectively.Log-rank test revealed that the rate of BCR in patients with apex and base PSM was higher than that in patients with negative surgical margin (P ＜0.001) or patients with apex-only PSM(P =0.002).Cox analysis indicated that higher preoperative PSA (P =0.040),higher pathological stage (P =0.041) and higher pathological Gleason score (P =0.004) were the independent predictors of BCR.PSM was not a predictive factor of BCR (P =0.257).Conclusions Preoperative PSA and pathological stage are the influencing factors of PSM.Higher preoperative PSA,higher pathological stage and higher pathological Gleason Score are the predictive factors of BCR.PSM may not be a predictive factor of BCR.The relationship between PSM and BCR needs further study.