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Objective To investigate the effect of tetrahydrobiopterin (BH4), superoxide dismutase-polyethylene glycol (PEG-SOD) and N(G)-nitro-L-arginine (L-NNA) on impaired endothelial progenitor cell (EPC) functions in DOCA-salt hypertensive mice. Methods DOCA-salt hypertension was created and systolic blood pressure was measured by tail-cuff methods. EPC was isolated from bone marrow of mice and characterized by flow cytometry and fluorescence microscopy. EPC of DOCA-salt mice was incubated with BH4, PEG-SOD, and L-NNA for 24 h, then in vitro EPC function assays were performed. Results Compared with control group, systolic blood pressure was significantly increased in DOCA-salt mice. Both EPC adhesion and angiogenesis functions were impaired in DOCA-salt mice compared to control animals, which were reversed by incubation with BH4, PEG-SOD and L-NNA. Conclusion BH4, PEG-SOD and L-NNA rescued the impairments from EPC functions in DOCA-salt hypertensive mice.
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PURPOSE: To identify the potential therapeutic role of postoperative radiotherapy (RT) in patients with locally advanced (stage II and stage III) gastric signet ring cell carcinoma (SRC).MATERIALS AND METHODS: Patients with locally advanced gastric SRC from the Surveillance, Epidemiology, and End Results program database between 2004 and 2012 were included in our study. Univariate and multivariate Cox proportional models were performed, and survival curves were generated to evaluate the prognostic effect of postoperative RT and surgery alone on SRC patients. Propensity score matching (PSM) was used to avoid selection bias among the study cohorts.RESULTS: We found that patients with postoperative RT had better probability of survival compared with those who did not receive RT (overall survival [OS], P<0.001; cancer-specific survival [CSS], P<0.001). After PSM, analysis of both overall and CSS showed that patients who underwent postoperative RT had better prognosis than those receiving surgery alone in the matched cohort (OS, P=0.00079; CSS, P=0.0036). Multivariate Cox proportional model indicated that postoperative RT had better effect on prognosis compared with surgery alone with respect to both overall (hazard ratio [HR], 0.716; 95% confidence interval [95% CI], 0.590–0.87; P=0.001) and CSS (HR, 0.713; 95% CI, 0.570–0.890; P=0.003).CONCLUSIONS: Postoperative RT had better prognosis compared with surgery alone for both overall and CSS for patients with locally advanced gastric SRC.
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Humans , Carcinoma, Signet Ring Cell , Cohort Studies , Nomograms , Prognosis , Propensity Score , Radiotherapy , SEER Program , Selection Bias , Stomach NeoplasmsABSTRACT
Objective:To explore the effect of interleukin-1α (IL-1 α) on the senescence of human umbilical vein endothelial cells (HUVECs) and the function of high mobility group protein 1 (HMGB 1).Methods:HUVECs were randomly divided into a control group,a IL-1α group (10 ng/mL IL-1α),a HMGB 1 group (100 ng/mL HMGB 1),and a HMGB 1 +IL-1α group (100 ng/mL of HMGB 1 plus 10 ng/mL of IL-lα).Senescence associated β-galactosidase (SA β-gal) staining was used to assess the number of senescent cells,Western blot were performed to detect the protein levels of silent information regulator 1(SIRT1),and quantitative real-time PCR (qRT-PCR) was used to detect the mRNA levels of p53,p21 and p 16.Restlts:Compared with the control group,the number of SA β-gal positive cells were significantly increased in the IL-1α group (P＜0.05),while the expression of SIRT1 protein significantly decreased (P＜0.01).Compared with the IL-1 α group,the expression of SA β-gal positive cells in the HMGB 1+IL-1α group was decreased and the mRNA levels of p21 and p53 were down-regulated (all P＜0.05),however,there was no statistical significance in the mRNA expression ofp16 (P＞0.05).Conclusion:IL-1α can induce the senescence of HUVECs,and HMGB1 may inhibit IL-1α-induced endothelial cell senescence via p53-p21 pathway.
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Objective To survey the awareness and knowledge of Helicobacter pylori (Hp) infection among medical staff in Shanghai.Methods A questionnaire survey was conducted among 316 medical staff in Shanghai,including 74 gastroenterologists (GI),158 general practitioners (GP),and 68 gastroenterology nurses(GN),from October 2014 to September 2015.The questionnaire was designed according to the Fourth Helicobacter Pylori Infection Treatment Consensus Report of China (the Consensus).There were 4 parts and 29 questions in the questionnaire,including the knowledge and performance of the Consensus (8 questions),the indications of Hp eradication (8 questions),detection methods of Hp infection (7 questions)and the therapy of Hp eradication (6 questions).Results Total 300 valid questionnaires were received with a response rate of 94.9％ (300/316).The awareness rate of the Consensus in GI,GP and GN groups was 81.1％ (60/74),57.6％ (91/158) and 26.4％ (18/68),respectively (χ2 =43.67,P=0.001).GI had higher awareness rate than GP and GN in indications of Hp eradications (for peptic ulcer,mucosa-associated lymphoid malignancies,post-resection patients of early gastric cancer,and family history of gastric cancer,the χ2 values were 16.68,35.60,33.46 and 39.22,respectively;all P ＜0.05).In part of Hp infection detection methods,the responses of GI,GP and GN groups in C14 or C13 urea breathing test were 97.3％ (72/74),47.5％ (75/158) and 82.1％ (55/68),respectively (χ2 =72.38,P =0.001);in gastric mucosa tissue rapid urease test were 70.3％ (52/74),13.9％ (22/158) and 25.4％ (17/68),respectively (χ2 =78.22,P =0.001);in serological test were 58.1％ (43/74),20.9％ (33/158)and 44.8％ (30/68),respectively (χ2 =40.30,P =0.001);in gastric mucosa tissue section staining were 56.8％ (42/74),13.3％ (21/158) and 22.4％ (15/68),respectively (χ2 =50.35,P =0.00).In part of Hp eradication therapy the responses of GI,GP and GN groups in recommended bismuth quadruple therapy were 71.6％ (53/74),47.5％ (75/158) and 40.3％ (25/62),respectively (χ2 =15.93,P =0.001);in triple therapy were 27.0％ (20/74),51.6％ (81/158) and 42.0％ (26/62),respectively (χ2 =12.42,P =0.002);in 10 or 14 d for treatment duration were 78.4％ (58/74),78.5％ (124/158)and 67.6％ (46/68),respectively (χ2 =3.36,P =0.186).Conclusion Gastroenterologists are more likely to adhere with the Consensus than general practitioners and gastroenterological nurses in the management of Hp infection.The survey suggests that more attention should be paid for popularization and implementation of Hp infection guidelines and consensus among Shanghai medical staff,especially for GP and nurses.
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AIM:To investigate the effects of human induced pluripotent stem cell-derived exosomes (hiPSC-exo) on cell viability, capillary-like structure formation , and senescence in endothelial cells exposed to high glucose .METHODS: Exosomes were isolated from the conditional medium of hiPSCs and confirmed by transmission electron microscopy , nanoparticle tracking analysis , and Western blot analysis using Alix and CD63 as markers.hiPSC-exo were labeled with PKH26 for tracking.Cultured HUVECs were treated with high glucose (33 mmol/L) with or without hiPSC-exo (20 mg/L) for 48 h, and cell viability, capillary tube formation, and senescence were assessed .RESULTS:hiPSC-exo showed a typical cup shape and could be taken up by human umbilical vascular endothelial cells (HUVECs) in a concentration-dependent manner.When exposed to high glucose, viability and tube formation in HUVECs was signifi-cantly reduced, whereas the proportion of senescent cells was higher compared to that in control HUVECs (P<0.01).Furthermore, hiPSC-exo restored cell viability and capillary-like structure formation , and reduced senescence in HUVECs exposed to high glucose (P<0.01).However, hiPSC-exo had minimal effects on normal HUVECs.Therefore, stem cell-derived exosomes can promote cell proliferation, enhance capillary-like structure formation , and reduce senescence in endothelial cells exposed to high glucose . CONCLUSION:Our study highlights the role of exosomes derived from hiPSC and may provide a new strategy for maintaining vascular health, preventing vascular aging , and avoiding pathological vascular remodeling that occurs in many diseases .
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Objective To investigate the status of knowledge and performance on Chinese Heart Failure Diagnosis and Treatment Guideline (2014 version) in general practitioners of Shanghai Pudong communities.Methods The survey was conducted from April to June in 2014 with a self-designed questionnaire.Total 390 general practitioners (GPs) in Pudong New Area were selected by cluster sampling method.The contents of questionnaire included:diagnosis and differential diagnosis,drug therapy,non drug therapy of chronic heart failure.Result Total 385 questionnaires were retrieved with a response rate of 98.7％ (385/390).The results showed that in aspect of diagnosis and differential diagnosis,373 (96.9％) Gps made the diagnosis based on history and physical examination,171 (44.4％)Gps never used BNP or NTPro-BNP tests,280 (72.7％)GPs did not know how to identify systolic or diastolic heart failure,86 (22.3％)Gps made the differential diagnosis according to the EF value.In aspects of drug therapy,the rate of beta blockers use was 10％-30％ in 284 (73.8％) Gps,149 (38.7％) Gps did not use beta blockers because of not knowing the contraindications,289 (75.1％) Gps used a maximum dose of betaloc for 25-50 mg,no one used 101-200 mg,242 (62.9％)Gps did not know the target dose of betaloc,the rate of ACEI/ARB use was 10％-30％ in 330 (85.7％) Gps,258 (67.0％) Gps would increase the dose but not knowing the target dose.The main reason for not using the target dose of Betaloc and ACEI/ARB was not knowing the dose.In aspect of non-drug therapy:240 (62.3％)Gps never heard of cardiac resynchronization therapy (CRT) and 271 (70.4％)Gps never heard of implantable cardioverter defibrillator (ICD).The senior rank GPs grasped the guideline much better than Gps with primary and intermediate professional ranks.Conclusion General practitioners in community health centers should further study the guideline of heart failure,particularly need to strengthen the knowledge and ability of drug therapy.
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Objective To investigate the changes of osteopontin (OPN) expression in murine colitis induced by dextran sodium sulfate (DSS) and its role in inflammatory bowel disease (IBD).MethodsThirty-two male BALB/C mice were randomly assigned into 4 groups: control group (group A), DSS-induced murine colitis model group (group B), salazosulfapyridine treatment group (group C) and infliximab treatment group (group D). Plasma OPN concentration was measured by enzyme linked immunosorbent assay (ELISA). OPN mRNA level was detect by using reverse transcriptase polymerase chain reaction (RT-PCR) and protein expression in colonic tissues was analyzed by using Western blotting. The location expression of OPN in colonic tissues was determined by immunohistochemical staining. ResultsIn group A, B,C and D, the plasma concentrations of OPN were (5.26±1.93) ng/ml, (10.21±2.37) ng/ml, (4.58±1.83) ng/ml and (4.82±1.83) ng/ml,respectively: the mRNA levels of OPN in colonic tissues were (0.36±0.16), (0.71±0.17),(0.32±0.07) and (0. 34±0. 08), respectively; the protein levels of OPN in colonic tissues were (0.44±0.10), (0.85±0.04), (0.61±0.11) and (0.58±0.17), respectively. The OPN-positive cell numbers in lamina propria mononuclear were (46.6±10.9), (155.5±43.8), (73.1±6.8) and (70.6±8.3), respectively. The expression of OPN in group B was significantly higher than that in group A (P<0.05). Compared with group B, the expressions of OPN in group C and D were significantly decreased (all P valus <0. 05). No significant difference was detected between group C and D. Conclusions The study shows that the expression of OPN significantly increased in DSS-induced murine colitis and decreased after treated with drugs. OPN-mediated immune response contributes to DSS-induced murine colitis.
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Objective To analyse the clinical characteristics,follow up their prognsis and evaluate the treatment of patients with Crohn' s disease (CD). Methods The data of patients with CD were collected at Zhongshan Hospital of Fudan University from 2002 to 2007. The diagnosis was made according to the consensus recommended by Chinese Society of Gastroenterology. The disease severity, follow-up and prognsis were evaluated according to the consensus. Results Sixty-six CD patients were enrolled in this study. The ratio of males to females was 2.47 : 1. Age at diagnosis ranged from 12 to 76 years old, and the mean age was (32 ± 17)years old. The main gastroenterological manifestations were abdominal pain (80.3 %), diarrhea (54.6 %), fistula formation (31.8%) ; and the main systemic manifestation was fever (80.3 %) and defective nutrition. A total of 60.6 % of patients with CD had complications and 34. 8% of these patients had more than one complications. Extraintestial manifastation were presented in 7.6% of patients with CD. A total of 86.4% of patients with CD were active state cases and 57. 6% were suffered from inflammation of ileum and colon. Abdominal pain (P = 0. 011), hematochezia (P = 0. 008), fever (P = 0. 001), anemia (P = 0. 020), underweight (P = 0. 010) and heightening of CRP (P = 0. 033) were more common in patients who were in active state than those who were in slient state. During their inducing alleviate treatment, 33.3% of patients with CD were treated with aminosalicylate alone, 36.4% were treated with both aminosalicylate and glucocorticoids, 7. 6% were treated with aminosalicylate, glucocorticoids and immunosuppressant. After medicine treatment, 6.8% of the patients relieved, 62.7% turned better, 28.8% were ineffective, 1.7% died, 55.9% recurd. And 21.2% were treated by surgical operation. A total of 42.4% of patients with CD had histroy of surgical operation and 9.1% were carried on more than one surgical operation.ConclusionsActive state patients with CD had high rate of complications, low extraintestial manifestatons, rare rate of dysplasia and canceration, and high rates of surgical operation and recurring.