Objective To study the effects of ETP-508,a novel endothelin receptor antagonist,on the proliferation of pulmonary arterial smooth muscle cells(PASMCs) of rat cultured in hypoxia environment.Methods Primary culture of rat PASMCs was prepared by the method of tissue block anchorage,and they were assigned into four groups: normoxia group(21% O2),hypoxia group(2% O2),hypoxia+BQ-485 group(10-6,10-7,10-8,10-9mol/L) and hypoxia + ETP-508 group(10-6,10-7,10-8,10-9mol/L).MTT(492nm) assay was used to detect the A value of the four groups after cells were cultured for 24,48 and 72h.Flow cytometry and radioimmunoassay were respectively used to detect the cell cycle and ET-1 content at 48h time point.Results MTT assay demonstrated that A value of each group did not significantly differ at 24h time point.At 28h time point,A value of hypoxia group was markedly increased(P

Objective The objective of this study was to investigate the levels of serum miR-21 and miR-34a in patients with advanced gastric cancer before and after Folfox chemotherapy and its relationship with chemotherapy efficacy.Methods Forty-five patients with advanced gastric cancer who underwent Folfox chemotherapy were enrolled from May 2015 to October 2015.The levels of miR-21 and miR-34a were analyzed by Real-time PCR before and after chemotherapy.The relationship between miR-21 and miR-34a levels and chemotherapy efficacy was analyzed.The predictive values of miR-21 and miR-34a on the efficacy of chemotherapy were evaluated by the receiver operating curve(ROC).Results After chemotherapy,6 cases(13.33%)were relieved,10 cases(22.22%)were stable disease(SD),29 cases(64.44%)were disease progress(PD),the objective response rate(ORR)was 13.33%,the disease control rate(DCR)was 35.56%,the median survival time was 8.1 months.The level of miR-21 was down-regulated and up-regulation for miR-34a after chemotherapy.They were statistically significant(P<0.05).The level of miR-21 in the chemotherapy group was lower than that in the ineffective group,and the level of miR-34a was higher than that of the ineffective group(P<0.05).MiR-21 was negatively correlated with the efficacy of chemotherapy(rs=-0.431,P<0.05),while miR-34a was positively correlated with it(rs=0.504,P<0.05).The median survival time was 7.6 months for low-level patients with miR-21 and 6.0 months for high-level patients.The median survival time of miR-34a patients was 5.5 months,compared with 8.3 months for high-level patients,with a statistically significant difference(P<0.05).The Log-Rank test showed that the median survival of patients with low miR-21 was higher than that of patients with high miR-21(P<0.05).The median survival of patients with high miR-34a was higher than that of patients with low miR-34a(P<0.05).The miR-21 combined with miR-34a in predicting chemotherapy efficacy under the curve(AUC)was 0.865,the sensitivity was 80.9% and the specificity was 89.8%.Conclusion miR-21 and miR-34a are correlated with chemotherapy efficacy median survival time of patients with advanced gastric cancer.

OBJECTIVE To provide references for clinical diagnosis of catheter-related bloodstream infections(CRBSIs) and focus on studying the spectras of pathogenic bacteria and the drug sensitiveness. METHODS A total of 137 patients enrolled from Jan 2005 to Dec 2007 in our hospital with positive catheter cultures were admitted to our retrospective analysis.Pathogenic bacteria,contaminant bacteria and the drug sensitiveness of main pathogenic bacteria were analyzed. RESULTS From them 80 patients were diagnosed CRBSIs.Among 92 strains of pathogenic bacteria,43(46.7%) strains were Gram-positives,31(33.7%) coagulase negative staphylococci(CNS) strains,31(33.7%) Gram-negative bacilli strains and 18(19.6%) were Candida strains. CONCLUSIONS CNS are the most common bacteria of CRBSIs,and the second are Candida.The common pathogen show multi-drug resistance.

BACKGROUND: Neuropeptides, a kind of endogenous active substance in nerve tissues, can modulate physiological functions of multiple body systems.OBJECTIVE: To observe the effects of vascular bundles or sensory nerve tracts implanted into tissue-engineered bone for rabbit large bone defects on the expression levels of calcitonin gene-related peptide (CGRP) and neuropeptide-Y.METHODS: Fifty-four New Zealand rabbits were enrolled to make model of large bone defects, and then, the animal models were randomly divided into three groups, including sensory nerve tract, vascular bundle, and control groups (n=18 per group), followed by implanted with sensory nerve tracts, vascular bundle, and tissue-engineered bone without sensory tracts or vascular bundle, respectively. The defected bone received gross and Masson staining at 4, 8 and 12 weeks after modeling, to compare the expression levels of CGRP and neuropeptide-Y in each group.RESULTS AND CONCLUSION: mRNA expression levels of CGRP and neuropeptide-Y in the sensory nerve tract and vascular bundle groups were significantly higher than those in the control group at different time points after modeling (P < 0.05). mRNA expression levels of CGRP and neuropeptide-Y in the tissue-engineered bone began to be increased and peaked at the 8th week, and then decreased (P < 0.05), which were the lowest at the 4th week (P < 0.05).Immunohistochemical staining results showed that CGRP was mainly found in the bridge, periosteum of newly born bones and around blood vessels; while neuropeptide-Y mainly localized in the medullary cavity and around blood vessels. These results indicate that the implantation of vascular bundle and sensory nerve tracts for bone defects can upregulate the expression levels of CGRP and neuropeptide-Y, and promote bone repair. However, sensory tract implantation may cause sensory impairment; thereafter, vascular bundle implantation is more suitable for ideal tissue-engineered construction to meet physical requirements.

Objective To evaluate the feasibility and efficacy of betadine solution irrigation of gastrointestinal tract for infection prevention during the procedure of natural orifice transluminal endoscopic surgery(NOTES).Methods Twelve female porcine were divided into control group(n =4)to receive lavage with 500 ml normal saline and experimental group(n =8)to undergo lavage with 500 ml normal saline followed by 200 ml betadine solution.Fluid from gastrointestinal tract(5 ml)were collected before and after lavage,and after NOTES for culture.Endoscopy was performed 24 hours after NOTES to observe possible existence of inflammation,ulcer or bleeding.The animals were sacrificed 3 weeks after NOTES to explore intra-peritoneal adhesions,abscesses and other infections.Results One swine died of diaphragmatic injury and the other 11 animals successfully survived for 3 weeks.In trans-gastric approach,the average bacterial load of the fluid was 17.5 x 103 CFU/ml before lavage.In control group,the average bacterial load of the fluid was 2.5 × 103 CFU/ml after lavage and 5.5 × 103 CFU/ml after NOTES,while those in experimental group were 0 CFU/ml and 7.5 CFU/ml,respectively.In trans-colonic approach,the average bacterial load of the fluid before lavage was 76.2 × 103 CFU/ml.In control group,the average bacterial load of the fluid was 19.5 × 103 CFU/ml after lavage and 21 × 103 CFU/ml after NOTES,while those in experimental group were 2.25 × 103 CFU/ml and 1 × 103 CFU/ml,respectively.No inflammation,ulcer or bleeding were observed by endoscopy at 24 hours after NOTES.More adhesion and abscess were found in the control group than in the experimental group.In experimental group with trans-colonic approach,only one case of adhesion was observed.Conclusion It is effective and feasible of using betadine solution irrigation of gastrointestinal tract in infection prevention during the procedure of NOTES.However,further clinical studies assessing the effectiveness and safety are still necessary.

Aim Series of compounds,which were considered to be the antagonists of ET-1 receptor,were synthesized by Beijing Institute of Pharmacology and Toxicology.The biological activity of these compounds was screened and some active compounds were selected for further pharmacological characterization on pulmonary hypertension.Methods Radioligand binding assay was performed to study the binding affinity of compounds for ETA and ETB receptors.The biological activity of compounds was evaluated in isolated rat aortic ring and in systemic arterial pressure(SAP)of anesthetized rat experiments.In addition,hypotensive effect of compounds was investigated on monocrotaline induced pulmonary hypertension in rats.Results Compounds bind to ETA receptor had over 10 000 fold higher affinity than to ETB receptor.Contraction induced by ET-1 in isolated rat aortic ring was inhibited by compounds,and 1 ?mol?L-1 ETP-508 shifted the cumulative concentration-contraction response curve to ET-1 to right with no change in the maximal response.In vivo,the increase in SAP induced by ET-1 〔3.7 ?g?(0.5 ml)-1?kg-1〕 was inhibited by 2 mg?kg-1 compounds by intravenous infusion.Furthermore,BQ-485 and ETP-508 by intravenous infusion(0.4 mg?h-1)significantly inhibited 80 mg?kg-1(sc)monocrotaline induced pulmonary hypertension in rats.Conclusions These results indicate that ETP-508 and BQ-485 are highly selective ETA receptor antagonists and significantly inhibite monocrotaline induced pulmonary hypertension in rats.

Objective To use hemin as a catalyst in the formation of disulfide bonds in the synthesis of linaclotide. Methods The linaclotide peptide was synthesized by the standard 9-fluorenylmethyl(Fmoc)solid-phase synthetic strategy. Wang resin and Trt-protected cysteine were used in the synthesis. Hemin was used in random oxidation of line linaclotide. The result was compared with those of air,dimethyl sulfoxide(DMSO),and I2 oxidation systems. Results and Conclusion Hemin is a highly effective catalyst for disulfide bond formation in linaclotide synthesis. It overcomes some disadvantages in oxidation reactions with conventional oxidative re-agents,and supplies a convenient way for the synthesis of peptide with concentrated disulfide bonds.

Objective To investigate clinical presentations,laboratory examinations,magnetic resonance imaging (MRI) appearances and treatment of hypertrophic cranial pachymeningitis (HCP).Methods The clinical data of 13 patients with HCP receiving comprehensive therapy in Huashan Hospital from January 2007 to January 2013 were analyzed retrospectively.Results The onset of HCP was mostly chronic with an average duration of 26.7 months.The main clinical manifestations of the 13 patients were chronic headaches (12/13) and cranial nerve paralysis (12/13).Inflammation markers and cerebro-spinal fluid (CSF) protein levels increased in patients with HCP and gradually became normal after the treatment.The MRI demonstrated local or diffused thickened dura located in tentorium (10/13),falx cerebrum (5/13),frontal lobe (4/13),temporal lobe (7/13) and parietal lobe (4/13).The signal intensity was isointense on T1-weighted MR images and hypointense on T2-weighted MR images.Enhanced MR images showed conspicuous enhancement of the dural edges.Corticosteroid therapy improved the clinical symptoms in 12 of 13 patients.Conclusions HCP typically causes headache and paralysis of multiple cranial nerves.Enhanced MRI shows characteristic manifestations.At present corticosteroid therapy is the treatment of choice followed by immunosuppressive agent and radiotherapy.

Objective To investigate the most sensitive methods for diagnosing spontaneous internal carotid artery dissection (sICAD) and spontaneous vertebral artery dissection (sVAD) respectively,for the sake of earlier and more accurate diagnosis.Methods Consecutive patients with sICAD and sVAD who visited the Department of Neurology and Radiology,Huashan Hospital Affiliated to Fudan University during 2008-2013 were retrospectively reviewed and the sensitivity of CT angiography (CTA),magnetic resonance T1-weighted fat-suppressed images (MR T1-FS) and digital subtraction angiography (DSA) for the diagnosis of sICAD and sVAD was compared.Results Eighty patients (62 male,18 female; mean age (45.7 ± 11.9) years) were included in the study.There were 99 arterial dissections in total,45 cases of sICAD,52 cases of sVAD and 2 cases of spontaneous middle cerebral artery dissections.The sensitivity of CTA,DSA and MR T1-FS for diagnosing sICAD was 97.5％ (39/40),90.0％ (36/40) and 69.6％ (16/23) respectively,while for sVAD was 89.8％ (44/49),84.6％ (44/52) and 100.0％ (27/27) respectively.Conclusions sICAD and sVAD have significant differences in many aspects including diagnostic strategies.CTA and MR T1-FS seem to be the most sensitive methods for the diagnosis of sICAD and sVAD respectively.Although DSA has been considered as the gold standard for the diagnosis of artery dissection,this imaging technique does not allow analysis of artery wall thickness,thus also has limitations.It is likely that the diagnostic sensitivity will be improved by combining CTA and MR T1-FS.

Objective To explore the outcomes of the transplanted kidney as donor for clinical renal transplantation and summarize experience in combination with related literature.Method This study retrospectively analyzed the clinical documents of one case of uremia receiving renal allograft transplantation with the transplanted kidney as the donor in one case of renal transplantation after brain death in February,2015.The donor was a 31-year-old man who received renal transplantation for uremia in November,2014 and obtained normal renal function.Two months later,the patient was brain dead because of neurologic disorder and donated his transplanted kidney.The serum creatinine of the donor was 167 μmol/L,and the glomerular filtration rate was about 35 mL/min befor donation.The recipient was 27 years old who needed transplantation because of chronic renal function failure and uremia.Preoperation tests showed that PRA was negative,and serum creatinine was 1 353 μmol/L.After separating and dissecting the donor kidney carefully,we perfused and compensated the kidney by Lifeport Organ Perfusion and Preservation Conveyor.The warm ischemia time was about 15 min.The renal vein of the donor was anastomized with right external iliac vein of the receptor,artery with right external iliac artery,and ureter with right centrifugal ureter.Result The operating time was more than 3 h.Postoperatively,the recipient was given the immunosuppressive regimen as tacrolimus,mycophenolate mofetil and methylprednisolone to prevent rejection.At 1 st day postoperation,the 24-h urine volume of the receptor was 5 000 mL,serum creatinine was declined gradually to a minimum of 180μmol/L,and there was trace urine protein.The renal function of patient recovered well by now.Meanwhile,the patient was still under the follow-up.Conclusion It is practical that using transplanted kidney as donor kidney for re-transplantation.There were certain clinical significance for shortening the waiting time of renal transplantation in uremia patients and relieving the shortage of transplant kidney.