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Objective:To evaluate the role of connexin43 (Cx43) in sevoflurane anesthesia-induced cognitive dysfunction in aged rats.Methods:Fifty-two healthy male Sprague-Dawley rats, aged 18 months, weighing 400-500 g, were divided into 4 groups ( n=13 each) using a random number table method: control group (C group), sevoflurane group (SEV group), sevoflurane plus sh-NC group (SEV+ sh-NC group) and sevoflurane plus sh-Cx43 group (SEV+ sh-Cx43 group). Sevoflurane anesthesia model was established by inhaling 3% sevoflurane for 6 h. In SEV+ sh-NC group and SEV+ sh-CX43 group, sh-NC 5 nmol and sh-CX43 5 nmol were transfected into the lateral ventricles, respectively, at 1 day before sevoflurane anesthesia.Morris water maze test was performed at 30 min before anesthesia and 1, 2 and 3 days after the end of anesthesia, and the rats were sacrificed at each time point after Morris water maze test, the brains were removed, and the hippocampi were isolated for microscopic examination of the pathological changes and for determination of the expression of Cx43, cleaved caspase-3 and cleaved caspase-9 (by using Western blot), and contents of interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and IL-6 (by enzyme-linked immunosorbent assay). Results:Compared with group C, the escape latency was significantly prolonged, and the number of crossing the original platform was reduced, and the expression of CX43, cleaved caspase-3 and cleaved caspase-9 was up-regulated, and the contents of IL-1β, TNF-α and IL-6 were increased in group SEV ( P<0.05). Compared with group SEV, the escape latency was significantly shortened, the number of crossing the original platform was increased, and the expression of CX43, cleaved caspase-3 and cleaved caspase-9 was down-regulated, the contents of IL-1β, TNF-α and IL-6 were decreased ( P<0.05), and the hippocampal pathological injury was reduced in group SEV+ sh-CX43, and no significant change was found in the indicators mentioned above in group SEV+ sh-NC ( P>0.05). Conclusion:Cx43 is involved in the pathophysiological mechanism of sevoflurane-induced cognitive dysfunction probably by inducing neuroinflammatory responses and cell apoptosis in aged rats.
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Objective:To investigate the expression of coxsackievirus-adenovirus receptor (CAR) in thymic carcinoma and the relationship between CAR and the antitumor activity of oncolytic adenovirus H101.Methods:The expression of CAR in thymic carcinoma tissues and cells were detected by RT-qPCR and Western blot. H101 expression and virus titers in Bcap-37, MP59 and T1889 cells after infection were detected by RT-qPCR and 50% tissue culture infectious dose (TCID 50). The proliferation activity and apoptosis rates of T1889 cells infected with H101 at different multiplicity of infection (MOI) were detected by CCK-8 and flow cytometry. CAR expression in T1889 cells treated with different concentrations of trichostatin A (TSA), a histone deacetylase inhibitor, was detected. H101 expression and virus titers in the TSA-treated and H101-infected cells were detected. Cell activity was detected by CCK-8. The phosphorylation levels of MARK and ERK1/2 and the expression of CAR at protein level in TSA-treated or TSA+ TBHQ (ERK activator) treated cells were detected. Results:CAR expression at both mRNA and protein levels were significantly lower in thymic carcinoma tissues than in adjacent normal tissues ( P<0.01), and lower in MP59 and T1889 cells than in thymic epithelial cells (TEC) and Bcap-37 cells ( P<0.01). H101 expression in MP59 and T1889 cells and the titers of H101 in culture supernatants were significantly lower than those in Bcap-37 cells ( P<0.01). Compared with Bcap-37 cell, the activity of MP59 and T1889 cells was significantly increased and the apoptosis rates were significantly decreased 48 h after H101 infection ( P<0.01). The expression of CAR at both mRNA and protein levels in T1889 cells treated with different concentrations of TSA increased in a dose-dependent manner. When T1889 cells were treated with 0.25 μmol/L of TSA, the expression of H101 at mRNA level and H101 titers were significantly increased ( P<0.05); the phosphorylation levels of MAPK and ERK1/2 proteins were continuously decreased; the expression of CAR was continuously increased. Compared with the TSA treatment group, the expression of CAR at protein level in the TSA+ TBHQ treatment group decreased significantly ( P<0.01), and the p-ERK1/2/ERK1/2 ratio increased significantly ( P<0.01). Conclusions:TSA could up-regulate CAR expression in thymic carcinoma by inhibiting the MARK/ERK1/2 pathway, thereby enhancing the antitumor activity of H101.
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Objective To investigate the effect of 2-h Ex Vivo Lung Perfusion (EVLP) on the pulmonary arterial endothelium by comparing the endothelium-dependent relaxation between EVLP group and fresh control group.Methods The lungs from 6 Swedish domestic pigs were divided into two groups:the right lungs as fresh control group and the left lungs as EVLP group.Lungs in EVLP group were perfused for 2 h.Pulmonary artery segments were obtained.The endothelium-dependent relaxation and pulmonary artery smooth muscle contraction were studied in organ bath.Results The contractions induced by U-46619 were 22.4 ± 2.2 mN and 24.5 ± 2.9 mN in two groups.The maximum endothelium dependent relaxations were 97 ± 0.67％ and 97 ± 0.68％ in two groups.The negative logarithm of 50％ relaxation (pEC50) was 6.74 ± 0.07 and 6.76 ± 0.07 in two groups.There was no statistically significant difference between the two groups.Conclusion The function of endothelium and smooth muscle of pulmonary artery was fully preserved after 2-h EVLP.
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Objective To understand the distribution and drug resistance of pathogens from patients with anastomotic fistula infection after esophageal cancer surgery, and provide basis for clinical diagnosis and treatment.Methods Patients were admitted to a hospital due to anastomotic fistula after esophageal cancer surgery between January 2012 and December 2015, microbial culture and antimicrobial susceptibility testing results of patients were retrospectively analyzed.Results 1 986 patients underwent radical resection of esophageal cancer within 4 years, 148 of whom developed anastomotic fistula, 104 (70.27％) were with positive microbial culture.A total of 197 pathogenic strains were isolated, 52(26.40％)and 145 (73.60％)strains were isolated from intrathoracic anastomotic fistula and cervical anastomotic fistula respectively;127 (64.47％)strains were gram-negative bacteria, the major were Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii, 62(31.47％) strains were gram-positive bacteria, the major were Staphylococcus aureus, Enterococcus spp., and Streptococcus viridans, 8 strains (4.06％) were fungi.49(47.12％) cases were with mixed pathogenic infection.The resistance rates of gram-negative bacteria to imipenem were 17.86％-47.62％, to polymyxin B was 0, resistance rates of Pseudomonas aeruginosa to other antimicrobial agents were all70％, Acinetobacter baumannii to most antimicrobial agents were all>50.00％;resistance rates of gram-positive bacteria to clindamycin and tetracycline were both>50.00％, to linezolid, vancomycin, and teicoplanin were all 0, resistance rates of Staphylococcus aureus to penicillin, oxacillin, and ciprofloxacin were all>60％,resistance rate of Enterococcus spp.to quinupristin/dalfopristin was 100.00％.Conclusion Postoperative anastomotic fistula combined with infection can affect the prognosis of patients after esophageal cancer surgery, regular monitoring on distribution and drug resistance of pathogens can provide the basis for initial empirical treatment, and is conducive to the early treatment and rational use of antimicrobial agents.
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Objective To investigate the risk factors of cervical esophagogastric anastomotic fistula after esophagectomy of esophageal cancer.Methods The retrospective case-control study was conducted.The clinicopathological data of 956 patients who underwent esophagectomy and cervical esophagogastrostomy from January 2012 to December 2016 in the First Affiliated Hospital of Zhengzhou University were collected.Patients underwent Sweet or Mckeown surgery.Observation indicators:(1) intra-and post-operative situations;(2) the risk factors analysis of cervical esophagogastric anastomotic fistula after esophagectomy;(3) follow-up situations.Follow-up using outpatient examination and telephone interview was performed to detect the esophagogastric anastomotic stenosis of patients up to February 2017.Measurement data with normal distribution were represented as the (x)±-s.Univariate analysis and comparison of count data were done using the chi-square test or Fisher exact probability method.Multivariate analysis was done using the Logistic regression model.Results (1) Intra-and post-operative situations:all the 956 patients underwent successful operations,including 107 with Sweet operation and 849 with Mckeown operation.Of 956 patients,336 received thoracotomy and 620 received thoracoscopic surgery.Tumors located in upper,middle and lower esophagus were respectively detected in 143,627 and 186 patients.Operation time,volume of intraoperative blood loss and number of lymph node dissected in 956 patients were (274 ± 67) minutes,(210 ± 167) mL and 18 ± 11,respectively.Of 956 patients,117 had cervical esophagogastric anastomotic fistula,with an incidence of anastomotic fistula of 12.24％ (117/956).Of 117 patients with cervical esophagogastric anastomotic fistula,2 had early stage fistula,110 had middle stage fistula and 5 had later stage fistula;12 were cured by two-tube method (stomach tube and nutrition tube),24 were cured by three-tube method (stomach tube,nutrition tube and chest tube or mediastinal tube),43 were cured by open neck incision dressing,15 were cured by fistula cavity drainage and 17 were cured by esophageal stent implantation.Sixteen patients died in hospital postoperatively,including 6 with cervical esophagogastric anastomotic fistula and 10 without cervical esophagogastric anastomotic fistula.Duration of hospital stay of 956 patients was (16± 11)days,and durations of hospital stay of patients with and without cervical esophagogastric anastomotic fistula were (39± 19) days and (13±6) days.Postoperative pathological examinations:873,9 and 74 patients were respectively diagnosed with squamous cell carcinoma,adenocarcinoma and other types of cancer.TNM staging:stage 0,Ⅰ,Ⅱ,Ⅲ,Ⅳ and unidentified stage were respectively detected in 135,110,325,376,1 and 10 patients.(2) The risk factors analysis of cervical esophagogastric anastomotic fistula after esophagectomy:univariate analysis showed that gender,age,history of diabetes,surgical method,tubular stomach production,operation time,postoperative pulmonary infection and postoperative aspirating sputum through fiberbronchoscope were risk factors affecting cervical esophagogastric anastomotic fistula after esophagectomy,with statistically significant differences (x2 =4.179,6.174,4.427,4.377,6.266,7.057,55.036,51.806,P＜ 0.05).Multivariate analysis showed that tubular stomach production,postoperative pulmonary infection and aspirating sputum through fiberbronchoscope were independent risk factors affecting cervical esophagogastric anastomotic fistula after esophagectomy,with statistically significant differences (OR =1.922,2.907,2.323,95％ confidence interval:l.203-3.070,1.682-5.023,1.235-4.370,P＜0.05).(3) Follow-up situations:908 of 956 patients were followed up for 2-62 months,with a median follow-up time of 28 months.During the follow up,21 of 111 patients with cervical esophagogastric anastomotic fistula were complicated with cervical esophagogastric anastomotic stenosis,59 of 797 patients without cervical esophagogastric anastomotic fistula were complicated with cervical esophagogastric anastomotic stenosis,showing a statistically significant difference in cervical esophagogastric anastomotic stenosis (x2-16.803,P＜0.05).Conclusion Tubular stomach production,postoperative pulmonary infection,postoperative aspirating sputum through fiberbronchoscope are independent risk factors affecting cervical esophagogastric anastomotic fistula after esophagectomy.