OBJECTIVETo discuss the changes in Wnt pathway inhibiting factors in esophageal precancerosis lesions induced by methyl benzyl nitrosamine (MBNA) and the effect of Gexia Zhuyu decoction.

METHODWistar rats were subcutaneously injected with MBNA (3.5 mg x kg(-1) for twice per week to establish the model. Since the 1st day after the model establishment, they were orally administered with Gexia Zhuyu decoction (16, 8 mg x kg(-1)). At the 10th week, esophageal tissues were collected to observe the pathological changes of esophageal mucosa, detect SFRP1, sFRP4, Axin1, Axin2 and GSK-3β mRNA levels.by fluorescent quantitation PCR analysis and β-catenin protein level by Western blotting.

RESULTBeing induced by MBNA, rats in the model group showed slight atypical hyperplasia in the histopathological examination. Compared with the normal group, Gexia Zhuyu decoction dose high and low groups showed no significant pathomorphological and histological changes. The model group showed lower gene transcription levels of esophageal tissues sFRP1, sFRP4, Axin1 and Axin2 (P < 0.05 or P < 0.01) and higher β-catenin protein expression level (P < 0.01) than the normal control group. The Gexia Zhuyu decoction low dose group showed higher gene transcription levels of esophageal tissues sFRP1, sFRP4, Axin1 and Axin2 (P < 0.05 or P < 0.01) and lower β-catenin protein expression level (P < 0.01) than the normal control group.

CONCLUSIONUp-regulated β-catenin protein level and down-regulated Wnt pathway could enhance Wnt pathway activity of MBNA-induced esophageal precancerous lesions. Gexia Zhuyu decoction could down-regulate the β-catenin protein level and up-regulate the transcription level of Wnt pathway inhibiting factors, but could not block MBNA-induced esophageal precancerosis lesions.

Animals ; Axin Protein ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Esophageal Diseases ; drug therapy ; genetics ; metabolism ; pathology ; Glycogen Synthase Kinase 3 ; genetics ; metabolism ; Glycogen Synthase Kinase 3 beta ; Humans ; Male ; Necrosis ; Nitrosamines ; adverse effects ; Proteins ; genetics ; metabolism ; Rats ; Rats, Wistar ; Wnt Proteins ; genetics ; metabolism ; Wnt Signaling Pathway ; drug effects

Objective To construct a recombinant adenovirus vector of Hairpin RNA specific for MRP1 gene and study its inhibition of MRP1 gene expression in K562/AS2 cell line resistant to AS_2O_3 (ATO). Methods A MRP1-specific hairpin RNA recombinant adenovirus vector was constructed and used to infected K562/AS2 cells. Expression level of MRP1 mRNA detected by real-time fluorescent quantitative PCR. MRP1 protein detected by flow cytometry. MTT method was used to detected the cytotoxicity of ATO and etoposide. Results MRP1 mRNA and protein expression level in K562/AS2 cells before and after the pAd-MRPl-shRNA adenovirus infection was (34.70±0.28 vs 4.19±0.03, P <0.05) and (26.40±0.16 vs 10.85±0.37, P<0.05), respectively. RR of K562/AS2 to arsenic trioxide and etoposide was (11.4078±0.3183 fold vs 1.6126±0.3015 fold, P<0.05) and (5.9141 ±0.0149 fold vs 1.7664±0.1038 fold, P <0.05), respectively. The reversal fold of ATO and etoposide was (7.2409±1.3668) and (3.3555±0.1886), respectively. Conclusion Successfully constructed pAd-EGFP-U6-shRNA-MRPl adenovirus vector, the vector of infection K562/SA2 cells can inhibit MRP1 gene expression and reverse the resistance of the ATO and etoposide.

Objective To investigate the reversal effect of Topo Ⅱα-shRNA and Topo Ⅱβ-shRNA on Topo Ⅱ gene in K562/AS2 cells. Methods Three pieces of Topo Ⅱα-shRNA and three pieces of Topo Ⅱβ-shRNA were designed,synthesized and transfected into K562/AS2 cells by liposome. Expression level of Topo Ⅱα and Topo Ⅱβ mRNA were determined by real time fluorescence quantitative PCR. The expressions of Topo Ⅱα and Topo Ⅱβ protein were assayed with flow cytometer. Results After treated with Topo Ⅱα-shRNA or Topo Ⅱβ-shRN A for 24 hours,the expression level of Topo Ⅱα mRNA and Topo Ⅱβ mRNA protein in K562/AS2 cells decreased at most (78.22±0.01) %,(31.17±1.27) % (P <0.05),and (57.36±0.01)%,(23.98±1.22) % (P <0.05) respectively. Conclusion The expression of Topo Ⅱ gene can be down-regulated after infected with Topo Ⅱ-shRNA in K562/ AS2 cell line.

Adult ; Arsenic ; pharmacology ; Chromosome Aberrations ; chemically induced ; Dose-Response Relationship, Drug ; Female ; Humans ; Lymphocytes ; drug effects ; metabolism ; Male ; Middle Aged

ObjectiveTo retrospectively evaluate the clinical efficacy of endoscopic submucosal tunnel resection for esophageal leiomyoma originating from muscularis propria.MethodsA total of 16 patients with esophageal mass originating from muscularis propria were recruited with informed consents from January 2011 to November 2011,and underwent esophageal submucosal tunneling endoscopic resection.ResultsAll lesions were completely resected.Histological examinations confirmed the diagnosis of leiomyona,and immunohistochemical staining indicated active hyperplasia in 9 cases.Intraoperative mediastinal,subcutaneous and retroperitoneal emphysema occurred in one patient,and the patient recovered one week later.No other complications or death were recorded.The patients were followed up for six months on average,and no cases of recurrence were found.ConclusionEndoscopic submncosal tunnel resection of esophageal leiomyoma originating from the muscularis propria is a minimally invasive,safe and effective procedure.

Objective To investigate the utility of plasma procalcitonin (PCT) as an early predictor for postoperative complications in patients who underwent elective pancreaticoduodenectomy (PD).Methods Clinical data of 87 patients who underwent elective PD in Changhai Hospital from March.1, 2016 to Dec.31, 2016 were collected.The general data, postoperative recovery, serum PCT level and white blood cell (WBC) count before, 1 d, 3 d and 5 d after PD were recorded.ROC curve was drawn and AUC was calculated to determine the cutoff value, sensitivity and specificity.Patients were divided into complication group (n=42) and noncomplication group (n=45) based on the occurrence of post-operative complications, and the comparisons between the two groups were performed.Results There were no significant differences on the age, gender, diabetes, obstructive jaundice, laboratory tests including PCT, operative time, blood loss volume during surgery and tumor type between the two groups, which were comparable.Complication group had longer hospitalization than noncomplication group (24 d vs 15 d,P<0.001), and the differences were statistically significant.In complication group, 18 patients had pancreatic fistula, 13 had peritoneal infection, 7 had gastric empty dysfunction, 8 had bleeding, 2 had bile fistula and 2 had incision infection after PD.The postoperative plasma PCT level in patients with gastric empty dysfunction, bleeding, bile fistula and incision infection was not statistically different from those in noncomplication group (all P>0.05), but the plasma PCT level in patients with pancreatic fistula and peritoneal infection on 3 d and 5 d after PD was significantly higher than those in noncomplication group, and the difference was statistically significant (all P<0.05).The combination of plasma PCT and WBC on 3 d and 5 d after PD was superior to PCT or WBC alone in predicting pancreatic fistula (sensitivity 88.9%, 72.7%;specificity 68.5%, 78.2%) and abdominal infection (sensitivity 100%, 100%;specificity 45.9%, 44.4%).Conclusions Plasma PCT could predict the occurrence of abdominal infection and pancreatic fistula after PD.The combination of PCT and WBC might be more valuable in predicting abdominal infection and pancreatic fistula.

Objective To investigate the short- to medium-term therapeutic effects of a new internal fixation device,intraosseous internal fixation(IO-FIX),in the foot-ankle arthrodesis.Methods From August 2016 to December 2018,32 patients(40 feet) underwent foot-ankle arthrodesis with IO-FIX at Department of Orthopaedic Surgery,The Ninth Peopled Hospital of Shanghai.They were 6 males and 26 females,aged from 23 to 83 years(61.7±15.1 years).There were 28 cases(36 feet) of hallux valgus,2 cases(2 feet) of ankle arthritis,one case(1 foot) of ankle rheumatoid arthritis and one case(1 foot) of naviculocuneiform arthrosis.The therapeutic effects were assessed in terms of imaging evaluation,American Orthopaedic Foot and Ankle Society(AOFAS) score,fusion rate and full weight-bearing time.Results The follow-up ranged from 3.0 to 31.3 months(mean,12.6 months).The total fusion rate was 95.0%(38/40);the total AOFAS score increased significantly from preoperative 41.9±9.5 to postoperative 86.9±4.7(P<0.05).The 28 patients(36 feet) with hallux valgus achieved a successful fusion rate of 97.2%(35/36) and full weight-bearing at 8 weeks after operation.Their fusion time ranged from 45 to 64 days(57.1 days).Their metatarsophalangeal angle was decreased significantly from 52.10±13.50 preoperatively to 13.40±4.90 postoperatively and their 1-2 intermetatarsal angle significantly from 14.5°±2.4°to 8.90±2.4°(P<0.05).Their AOFAS ankle-hindfoot score was improved significantly from 41.8±9.9 to 87.0±4.8(P<0.05).All the 3 cases of ankle arthrodesis achieved good bone union and full weight-bearing within 12 weeks and their AOFAS ankle-hindfoot score was improved significantly from preoperative 43.4±3.5 to 86.3±3.5 at the final follow-up.Conclusion In foot-ankle joint arthrodesis,due to advantages of stable fixation,zero profile,limited soft tissue irritation,reinforced bone bridge and easy reproducibility,10-FIX can lead to satisfactory short- to mid-term therapeutic effects.

Objective To discuss the clinical use of radiotherapy in the treatment of giant vascular malformation. Methods Six patients with giant vascular malformation in oral and maxillofacial region were treated by three dimensional radiation therapy in Department of Stomatology, The Second Affiliated Hospital,School of Medicne, Zhejiang University in the last ten years and the cilinical data were reviewed. The treatment results were evaluated by clinical examination and radiology. Results No complication was observed during and after the radiotherapy. All patients were satisfied with the aesthetic results. The lesions in MRI were all reduced and even disappeared. There was no sign of recurrence during the follow-up period.Conclusions Three dimensional radiotherapy is safe and effective for oral and maxillofical vascular malformation.

OBJECTIVENeurally adjusted ventilatory assist (NAVA) is a new mode of mechanical ventilation that delivers ventilatory assist in proportion to neural effort. This study aimed to compare the hemodynamic safety, oxygenation and gas exchange effects ventilated with NAVA and with pressure support ventilation (PSV) in infants who underwent open-heart surgery.

METHODSTwenty-one infants who underwent open-heart surgery for congenital heart disease (mean age 2.9+/- 2.1 months and mean weight 4.2+/- 1.4 kg) were enrolled. They were ventilated with PSV and NAVA for 60 minutes respectively in a randomized order. The hemodynamic, oxygenation and gas exchange effects produced by the two ventilation modes were compared.

RESULTSThree cases failed to shift to NAVA because of the bilateral diaphragmatic paralysis after operation. In the other 18 cases, there were no significant differences in the heart rate (HR), systolic blood pressure (BPs) and central venous pressure (CVP) in the two ventilation modes. The PaO2/FiO2 (P/F) ratio in NAVA was slightly higher than in PSV, but there was no statistical difference. PaCO2 did not show significant differences in the two modes. The peak inspiratory pressure (PIP) and electrical activity of the diaphragm (EAdi) in NAVA were significantly lower than in PSV. The EAdi signal after extubation was higher in infants who needed reintubation or intervention of noninvasive mechanical ventilation than in those who were extubated successfully (30.0+/- 8.4 microV vs 11.1+/- 3.6 microV; P<0.01).

CONCLUSIONSAs the first study of application of NAVA in infants in China, this study shows that NAVA has the same homodynamic effects as PSV. However the PIP for maintaining the same level of PaCO2 in NAVA is significantly lower than that in the traditional PSV. Monitoring the EAdi signal after extubation may show the risks of reintubation or intervention of noninvasive mechanical ventilation.

Female ; Heart Defects, Congenital ; physiopathology ; surgery ; Hemodynamics ; Humans ; Infant ; Male ; Respiration, Artificial ; methods

Purpose To investigate the effect of grape seed proanthocyanidins on the phenotype-transforming marker protein expression of db/db renal cells in mice model of type 2 diabetes,and to explore the protective mechanism of grape seed extract on diabetic renal injury in db/db mice.Methods Male db/db diabetic mice were randomly divided into two groups:diabetic group (db/db group) and diabetic + grape seed proanthocyanidin extract group (db/db + GSPE).The same week-old male db/m mice was used as normal controls (db/m) and grape seed proanthocyanidin extract gavage treatment group (db/m +grape seed proanthocyanidin extract group,db/m + GSPE).The mice of db/db + GSPE group and db/m + GSPE group were administered daily with grape seed proanthocyanidin extract (5mg/kg) by gavage.Results Renal tissues of db/db diabetic mice showed increased expression of α-SMA,p-p38MAPK,pERK1/2 and 8-OHdG level,and down-regulation in E-cadherin expression compared with db/m group (P ＜ 0.05).However,the alternations of α-SMA,p-p38,p-ERK1/2,E-cadherin protein levels,and 8-OHdG level,in db/db group were reversed by addition of grape seed proanthocyanidin extract (P ＜ 0.05).Conclusion Grape seed proanthocyanidin extract inhibits the epithelial to mesenchymal transition (EMT) associated protein,by decreasing ROS production,and activating p38 MAPK and ERK1/2.These findings suggest that grape seed proanthocyanidin extract provides a treatment option for diabetic nephropathy.