Background: Inflammatory bowel disease (IBD) is a non-specific inflammatory disease of the gastrointestinal tract with a course of repeated episodes and remissions. Vedolizumab (VDZ), a selective blocker of interaction between leukocytes and vascular endothelium of the gut, has been demonstrated effective in treatment of active IBD. Aims: To systematically evaluate the efficacy and safety of VDZ for active IBD. Methods: PubMed, Embase, Cochrane Library and Google Scholar were retrieved to collect randomized controlled trials (RCTs) comparing VDZ and placebo in patients with IBD published in English before Aug. 2018. Meta-analysis was conducted by using RevMan 5.30 software. Results: Eight RCTs involving 3 159 active IBD patients were included. Meta-analysis showed that VDZ was superior to placebo in inducing clinical response, clinical remission and endoscopic remission in active UC (RR=1.62, 95% CI: 1.33-1.97, P<0.000 01; RR=2.45, 95% CI: 1.56-3.83, P<0.000 1; RR=1.75, 95% CI: 1.29-2.37, P=0.000 3, respectively) and in maintenance of clinical remission in inactive UC (RR=2.43, 95% CI: 1.73-3.41, P<0.000 01). Also, VDZ was superior to placebo in inducing clinical response and clinical remission in active CD (RR=1.47, 95% CI: 1.21-1.79, P=0.000 1; RR=1.87, 95% CI: 1.37-2.56, P<0.000 1, respectively). Subgroup analysis revealed that clinical remission was only achieved in CD patients naive to anti-tumor necrosis factor-α (TNF-α) therapy. Only one trial described the clinical remission in inactive CD, the results showed that VDZ was superior to placebo. Except for nasopharyngitis, adverse events were similar between VDZ group and placebo group. Conclusions: VDZ is safe and effective for induction and maintenance of remission in active IBD, but may be not more effective than placebo in CD patients failure to anti-TNF-α therapy.

Objective:To evaluate the value of pretreatment 18F-fluorodeoxyglucose (FDG) PET/CT-based heterogeneity for early prediction of targeted therapy outcome in patients with human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer. Methods:From May 2012 to April 2018, 29 patients (all females, median age: 52 (32-69) years) who had HER2 positive metastatic breast cancer and underwent pretreatment 18F-FDG PET/CT in Fudan University Shanghai Cancer Center were retrospectively enrolled. All patients received trastuzumab as first-line treatment and were followed up for 6-87 (median time: 35) months. The relations between clinicopathologic parameters or PET/CT-based parameters and progression-free survival (PFS)/overall survival (OS) were analyzed with Cox univariate analysis. The parameters with P≤0.01 were further analyzed with Cox multivariate analysis. Optimal cut-off values were determined by time-dependent receiver operating characteristic (ROC) curve analysis. The survival analyses were estimated by Kaplan-Meier method and log-rank test. Results:The median OS of the 29 patients was 30 (6-83) months, and the median PFS was 10 (2-29) months. The PET/CT-based heterogeneity index(HI), including the maximum standardized uptake value (SUV max) ratio (SUV max-R; hazard ratio ( HR)=8.6, 95% CI: 2.7-27.8, P<0.001), the mean standardized uptake value (SUV mean)-2.5 (the cut-off value of standardized uptake value (SUV)=2.5) ratio (SUV mean-2.5-R; HR=2.6, 95% CI: 1.2-5.9, P=0.020), the metabolic tumor volume(MTV)-2.5 ratio(MTV-2.5-R; HR=2.4, 95% CI: 1.1-5.2, P=0.030), and the total lesion glycolysis(TLG)-2.5 ratio(TLG-2.5-R; HR=3.2, 95% CI: 1.4-7.4, P=0.008) of the lesion with the highest SUV max to that with the lowest SUV max, were significantly associated with PFS. None of the parameters was significantly associated with OS (all P>0.05). Multivariate analysis showed that the SUV max-R was the only independent predictor for PFS ( HR=6.8, 95% CI: 1.8-26.1, P<0.01). Area under the ROC curve for SUV max-R was 0.747. With a cut-off value of 1.8, SUV max-R could effectively distinguish the benefit from non-benefit population treated with trastuzumab (15.0 vs 7.0 months; χ2=18.68, P<0.01). Conclusion:Pretreatment 18F-FDG PET/CT-based HI has potential value for early prediction of first-line trastuzumab treatment outcome in patients with HER2 positive metastatic breast cancer.

Objective To investigate the expression and significance of CXCL 9 in systemic lupus erythematosus (SLE ) . Methods The level of CXCL9 in peripheral blood from 20 patients with SLE and 20 normal controls were measured by enzyme linked immunosorbent assay .Compare the difference of the expression level of CXCL 9 in peripheral blood between two groups and analyzed their correlation with ages ,duration ,SLE diseases activity index (SLEDAI) .Results The level of CXCL9 in peripheral blood in patients with systemic lupus erythematosus was (1 549 .14 ± 362 .74)pg/L ,but in normal controls was(602 .54 ± 83 .70)pg/L .The level of CXCL9 in peripheral blood in patients with systemic lupus erythematosus was obviously higher than that in controls by statistical analysis ,there was significant difference between the two groups (P<0 .01) .The expression level of CXCL9 in pe‐ripheral blood of patients with systemic lupus erythematosus was positively correlated with SLEDAI (r=0 .892 ,P<0 .01) .Conclu‐sion CXCL9 may be involved in the pathogenesis of systemic lupus erythematosus .

ObjectiveTo investigate the effects of losartan on angiotensin (Ang)Ⅱ-induced the generation of oxidative stress and expression of transforming growth factor β1(TGF-β1) in rat proximal tubular epithelial cells and to explore its underlying mechanism. MethodsNRK-52E cells, a rat proximal tubular epithelial cell line, were applied to explore the antioxidationand antifibrosis of losartan. The expression of three subunits of nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase, including p47phox, Nox-4, p22phox, and TGF-β1 were determined by real-time RT-PCR and/or Western blot. The generation of reactive oxygen species (ROS) was measured by DCF fluorescence analysis. Superoxide dismutase (SOD) in the supernatant was measured by colorimetric method. Results10-7 mol/L Ang Ⅱ up-regulated p22prox, p47phox and Nox-4 mRNA and protein expression, and the mRNA increased by 5.57-fold, 5.55-fold and 9.41-fold at 24 h (P<0.01, respectively) and the protein increased by 4.53-fold, 4.17-fold and 6.50-fold at 24 h (P<0.01, respectively) as compared with control. Losartan greatly reduced the mRNA elevation of p22prox, p47phox and Nox-4 by 2.71-fold, 2.18-fold and 5.23-fold (P<0.01, respectively) and reduced the protein elevation by 3.20-fold, 2.30-fold and 4.30-fold (P<0.01, respectively) as compared with control. Losartan also inhibited ROS generation induced by Ang Ⅱ in rat proximal tubular epithelial cells. SOD level in the supernatant was markedly decreased after Ang Ⅱ stimulation, while losartan could increase SOD levels (P<0.01). Furthermore, losartan signficantly inhibited Ang Ⅱ-induced TGF-β1 mRNA up-regulation by 64% (P<0.01). ConclusionsLosartan acts as an anti-oxidative and anti-fibrotic agent via the mechanisms of blocking NADPH oxidase-dependent oxidative stress and inhibiting TGF-β1 expression.

Objective]To study the feasibility of Cartilage engineering using fibrin gel and chondrocyte cell sheets.[Methods]rabbit auricular chondrocytes were isolated and cultured to form cell sheets in flasks. The cell sheets were harvested using cell scrapers,and cut into fragments. The two precursor solutions of Fibrin gel were used to suspend the cell sheet fragments and isolated chondrocytes,and then added into the wells of a 48-well plate to form Gelatinous chondroid disc constructs. After in vitro culture, the constructs were implanted into nude mice. After 8 weeks,the constructs were harvested,and the specimens were evaluated using grossly observing, histological and immunohistochemical observation. [Results]Mature cartilage discs were obtained. The histomorphology of the explanted discs appeared non-uniform cartilaginous tissue comprise of regenerated cartilage islands with different size and irregular shape. Immunohistochemistry staining demonstrated that type II collagen highly expressed in the ECM of the cartilage islands. In 1 of the 8 discs,partial ossification was observed.[Conclusion]Fibrin gel is a favourable carrier. Artificial cartilage with stereochemical structure was constructed via combining the fibrin gel and chondrocyte cell sheets.

Objective To investigate the effect of simulated microgravity on growth , morphology, protein expression and virulence gene expression of Klebsiella pneumoniae (KPN).Methods KPN was divided into simulated microgravity group and control group in the experiment .The former group was in the ambient of simulated microgravity in a clinostat .The bacterial growth curves , morphologyical changes in electron microscopy , and protein expression were detected by SELDI-TOF-MS, and the expression of 4 virulence genes(ureA,wabG,uge and fimH) by real-time fluorescence quantitative PCR (RT-PCR) in both groups.Results Compared with the control group , the growth of KPN under simulated microgravity was accelerated , and the total bacterial count increased in microgravity group .The bacterial morphology in microgravity group was changed under scanning electron microscopy (SEM), and thinner and longer bacteria were increased .The transmission electron microscopy ( TEM) analysis revealed increase in cytoplasmic granular substance in microgravity group .Proteome analysis showed that the expression of 18 proteins was changed , half of which up-regulated and the rest were down-regula-ted.Those 18 proteins were searched in the protein library .And 21 proteins of a similar molecular mass were retrieved ,13 of which,proteins with known functions ,were closely related to bacterial life activities .RT-PCR results showed that four virulence genes of KPN were down-regulated.Conclusion Upon exposure to simulated microgravity , the growth and repro-duction of KPN are accelerated and enhanced .The bacterial morphology is changed .The strain′s protein expression and four virulence genes expressionare also changed .Therefore,microgravity can change the characteristics of KPN .

Objective To retrospectively analyze medical data of patients with colorectal cancer (CRC) so as to provide evidence for clinical use of opportunistic screening.Methods A total of 2450 CRC patients (male 1377,female 1073) who were treated at five hospitals in North China during October 2001 and September 2011 and had complete medical records and pathological results were recruited.The correlations of incidenceofCRCwithage,gender,tumorlocationandhistologicaltypeswere analyzed.Results Of all the CRC patients,those less than 50 years old accounted for 18.14％ ; and the incidence of CRC was substantially increased in those over 50 years old.Seventy-three percent of tumor occurred at the rectum and sigmoid colon,6％ at descending colon,7％ at transverse colon and 14％ at ascending colon.Moderately,well or poorly differentiated adenocarcinoma accounted for 50.33％,40.35％and 9.32％,respectively.Histological differentiation was not correlated with age and gender ( P ＞ 0.05 ).Conclusions Age and gender should not be considered a determination of opportunistic screening for CRC.Colonoscopy is recommended as an alternative CRC screening procedure.

BACKGROUND:To seek for ideal scaffold materials is still an important task for cartilage tissue engineering.OBJECTIVE:To investigate the application of the AviteneTM microfibrillar collagen hemostat sponge in cartilage tissue engineering.METHODS:Rabbit auricular cartilage was harvested via surgical operation,and primary chondrocytes were isolated and amplified.Microfibrillar collagen hemostat sponge was cut into small bricks.The passage 2 chondrocytes were suspended and seeded onto the spongy bricks.After 1 week of in vitro culture,the constructs were then implanted into nude mice.After 8 weeks,the specimens were collected and evaluated using gross,histological and immunohistochamical observation.RESULTS AND CONCLUSION:During the cell seeding,the scaffold maintained its dimensions.No shrinkage was observed when the cell suspension was added.There was no considerable change in dimensions during the 1-week in vitro culture and at 8 weeks after implantation in nude mice.At 8 weeks post-implantation,mature cartilage blocks were harvested,which were white,translucent,and flexible.Histologically,the constructs appeared to have typical mature cartilaginous tissues,with robust extracellular matrix secretion,in which the microfibrillar collagen was incompletely degraded.We conclude that the microfibrillar collagen is a favorable scaffold material for cartilage tissue engineering.

BACKGROUND:The cell-sheet technology, based on a temperature-responsive culture, has been drawing more and more attention;however, the temperature-responsive culture dish is quite expensive. Therefore, it is imperative to develop a substitutive technique.OBJECTIVE: To study the feasibility of cell-sheet ulturing using common culture dish, and investigate the chondrogenesis of the cell sheet. METHODS: A piece of nasal septal cartilage was adopted from a patient with deviation of nasal septum to extract primary chondrocytes that were then cultured and amplified. The passage 3 chondrocytes were used to construct ell sheets. Monolayer cell sheet was formed by intensive culturing and allowing the extracellular matrix secretion. Bilayer cell sheet was constructed by seeding passage 2 chondrocytes on the monolayer cell sheet. The cell sheets were harvested using cell scraper, their properties were investigated prior to plantation into nude mice to construct the tissue-engineered cartilage. RESULTS AND CONCLUSION: Both bilayer and monolayer cell sheets with soft tremellose structures showed no significant difference through naked eyes. The newly harvested cell sheets appeared to have good fluidity and gelation. Eight weeks after mplantation into the nude mice, mature cartilage blocks were obtained. Histologically, the cell sheets were thin films composed by layered chondrocytes and extracellular matrix. Glycosaminoglycan formation and type Ⅱ collagen expressions were observed in the cell sheets cultured in vitro. The explanted samples exhibited ature cartilaginous tissue at 8 weeks after implantation. Biochemical analysis showed that the DNA contents of the neocartilages were higher than those of native human costal cartilage, while the contents of glycosaminoglycan and hydroxyproline were similar to native human nasal septal cartilage. To conclude, the hondrocyte cell sheets are likely to be constructed and harvested successfully using common culture dish, and the cell sheets exhibit favourable chondrogenesis.

ObjectiveTo explore the expression of hemopoietin(EPO) mRNA on cerebral ischemia-reperfusion injury in rats brain tissue and the effect of Tongxinluo on it.Methods The model of rat (MCAO) were perfused with Tongxinluo,the changes of neural stem cell proliferation and differentiation related cell factors of EPO mRNA were detected after ischemia-reperfusion injury 3、5、7、14 d by means of reverse transcriptase polymerase chain reaction(RT-PCR).ResultsEPO mRNA of ischemia-reperfusion models showed expression in different period,the expression enhanced in the third day,reached the highest in the fifth day; the ischemia side EPO mRNA expression enhanced in the third day after give Tongxinluo,in the 5,7 and 14 day,PCR expression gray values were higher than the model group.ConclusionEPO mRNA expression enhanced after cerebral ischemia,this expression can be strengthened by Tongxinluo,and may further induce neural stem cell proliferation and differentiation.