Objective To study the association of ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) promoter region methylation with human esophageal cancer. Methods Promoter region methylation of UCHL1 was dctcctcd by rnethylation specific PCR (MSP) in esophageal cancer cell lines and tissue samples.The expression of UCHL1 was detected by semi-quantitative RT-PCR and Western blot in esophagcal cancer cell lines.5-Aza-2'-deoxycytidine (5-Aza) was applied to reactivate methylated cell lines.ResultsComplete methylation of UCHL1 promoter region was detected in 8 cell lincs (KYSE30,KYSE150,KYSE140,KYSE450,KYSE510,TE3,TE7,TE10).Loss of UCHL1 expression was found in7 cell lines ( KYSE30,KYSE150,KYSE140,KYSE450,KYSE510,TE3,TE7).Reduced expression was found in TE10 cell line. Promoter region hypermethylation was correlated with UCHL1 expression in esophageal cancer cell lines.Re-expression of UCHL1 was induced by 5-Aza treatment in KYSE150 and TE3 cell lines.UCHL1 was frequently methylated in human primary esophageal cancer (74.51％,38/51 ),while no methylation was detected in normal esophageal mucosa (0/10). No association was found between promoter region methylation and age,gender,tumor location,tumor stage or lymph node metastasis.Conclusions UCHL1is silenced by promoter region hypermethylation in human esophageal cancer.Methylation of UCHL1 is frequently happened to primary esophageal cancer and may play an important role in the tumorigenesis.

Objective To investigate the prognostic factors of life and functional outcome of the first hemiparetic stroke patients. Methods One hundred and eighteen stroke subjects were registered prospectively. The Barthel index (BI) , Rankin scale (RS) , Mortricity index(MI) , Mini-mental state examination (MMSE) , Montgomery-Asberg depression scale (MADRS) and a scale of general state and risk factors were used to evaluate at the 48th hour, the 15th day and the 90th day after stroke. Results The patients' performance, as demonstrated by their scores with all the evaluation instruments, changed significantly at all the time points of evaluation after stroke (P ＜0.05). There was no significant difference between the performance at the 48th hour and the 15th day after stroke ( P ＞ 0.05 ). But at the 90th day after stroke, the activity of daily living performance and the depression status recovered significantly (P ＜ 0.01 ). Logistic regression analysis showed that, such factors as pneumonia, urinary incontinence within 48th hour and deep sensation disturbance might adversely influence patients' activity of daily living performance at the 90th day after stroke; the muscle strength of upper extremities at the 48th hour, and MMSE scores at the 15th day after stroke acted as the protective factors. Conclusions The stroke patients improved significantly with regard to their clinical and functional manifestations when evaluated 90 days after stroke onset. The main factors influencing the activity of daily living performance 90 days after stroke onset included deep sensation disturbance,pneumonia, urinary incontinence and muscles strength of upper extremities at 48th hour, and MMSE scores at the 15th days after onset.

Objective To evaluate the effect of age on the median-effective target plasma concentration (EC50) of propofol inhibiting body movement evoked by gastroscopy in the patients.Methods Ninety adult patients of both sexes,of ASA physical status Ⅰ or Ⅱ,with body mass index 19-25 kg/m2,scheduled for elective gastroscopy,were divided into 3 groups according to age (n =30 each):18-39 yr group (Ⅰ group),40-64 yr group (Ⅱ group) and 65-85 yr group (Ⅲ group).In Ⅰ,Ⅱ,Ⅲ groups,propofol was given by target-controlled infusion with the initial target concentrations of 2.5,2.0 and 1.5 μg/ml,respectively,and gastroscopy was performed when the target concentration was achieved.Body movement was defined as the directional movement in head or four extremities during gastroscopy.The target plasma concentration of propofol was determined by up-and-down sequential trial.Each time the plasma concentration of propofol increased/decreased by 0.5 μg/ml in the next patient depending on whether or not body movement developed.The EC50 and 95 ％ confidence interval of propofol inhibiting gastroscopy-evoked body movement were determined using Probit analysis.Results The EC50 (95 ％ confidence interval) of propofol was 4.2(3.8-4.5),4.1(3.7-4.4) and 2.4(1.8-2.7) μg/ml in Ⅰ,Ⅱ and Ⅲ groups,respectively.There was no significant difference in the EC50 of propofol between group Ⅱ and group Ⅰ.The EC50 of propofol was significantly lower in group Ⅲ than in Ⅰ and Ⅱ groups.Conclusion Age affects propofol-induced analgesia in patients with visceral pain,and the potency of propofol inhibiting visceral pain during gastroscopy in the elderly patients is significantly enhanced as compared with that in the young and middle-aged patients.

Objective To study effect of virus inactivation/removal treated by solvent/detergent method and dry heating at 80℃, 72 h for inactivation in human coagulation factor Ⅷ.Methods Human coagulation factor Ⅷextracted from healthy human plas-ma were treated by solvent/detergent method and dry heating at 80℃, 72 h for inactivation .The virus inactivation effect was validated by adding the indicator virus ( PRV, Sindbis, HIV, EMCV, PPV).Results The methods could effectively inactivate lipid-enveloped and non lipid-enveloped viruses which could be used for virus inactivation /removal during human coagulation factor Ⅷexperiments , the residual amount of TNBP in production was less than one percent ten thousand (10 ppm), the residual Tween-80 concentration was less than one percent hundred thousand (100 ppm),which all met the safety standards .Conclusion and no significant change was ob-served in the activation and other indicators of human coagulation factor Ⅷ.

Objective To study the relationship among the sense of organizational fairness, innovative self-efficacy (ISE) and innovative behavior in nurses. Methods A total of 392 nurses from a grade A tertiary hospital were selected as the research subjects using convenience sampling method. The Organizational Fairness Scale, Innovation Self-efficacy Scale, and Innovation Behavior Scale were used to evaluate the sense of organizational fairness, ISE, and innovation behavior, respectively. The mediate equation model was constructed, and Bootstrap analysis was applied for validation. Results The scores for organizational fairness, ISE, and innovative behavior among the nurses were (67.8±15.2), (23.9±3.5), and (30.5±6.7) points, respectively. Organizational fairness score was positively correlated with both innovative behavior and ISE scores ［correlation coefficients (r) were 0.38 and 0.36, respectively, both P<0.01］. ISE score was positively correlated with innovative behavior total score (r=0.51, P<0.01). The results of the mediation analysis indicated that the total effect of organizational fairness on innovation behavior was 0.34 (P<0.01),with a direct effect of 0.17 (P<0.01). ISE plays a mediating role between organizational fairness and innovation behavior among nurses(P<0.01) with standardized mediation effect of 0.17, accounting for 50.0% of the total effect. Conclusion Organizational fairness can influence the ability of innovative behavior directly or through the mediating role of ISE.

Purpose/Significance Taking Jiashan county's chronic disease management mode based on blockchain as an example,new strategies for chronic disease management under the integrated county medical community mode are discussed.Method/Process U-sing the PEST-SWOT analysis method,the paper analyzes the strengths,weaknesses,opportunities and threats of the chronic disease management mode based on blockchain in Jiashan county from 4 aspects:politics,economy,society,and technology.Result/Conclu-sion The chronic disease management mode based on blockchain technology can ensure seamless connection and sharing of data,guaran-tee the security and traceability of patients'personal information and health records,and promote the common development of blockchain technology and chronic disease management in Jiashan county.

BACKGROUND: Gene promoter methylation is a major epigenetic change in cancers, which plays critical roles in carcinogenesis. As a crucial regulator in the early stages of B-cell differentiation and embryonic neurodevelopment, the paired box 5 (PAX5) gene is downregulated by methylation in several kinds of tumors and the role of this downregulation in esophageal squamous cell carcinoma (ESCC) pathogenesis remains unclear. METHODS: To elucidate the role of PAX5 in ESCC, eight ESCC cell lines, 51 primary ESCC tissue samples, and eight normal esophageal mucosa samples were studied and The Cancer Genome Atlas (TCGA) was queried. PAX5 expression was examined by reverse transcription-polymerase chain reaction and western blotting. Cell apoptosis, proliferation, and chemosensitivity were detected by flow cytometry, colony formation assays, and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assays in ESCC cell lines with PAX5 overexpression or silencing. Tumor xenograft models were established for in vivo verification. RESULTS: PAX5 methylation was found in 37.3% (19/51) of primary ESCC samples, which was significantly associated with age (P = 0.007) and tumor-node-metastasis stage (P = 0.014). TCGA data analysis indicated that PAX5 expression was inversely correlated with promoter region methylation (r = -0.189, P = 0.011 for cg00464519 and r = -0.228, P = 0.002 for cg02538199). Restoration of PAX5 expression suppressed cell proliferation, promoted apoptosis, and inhibited tumor growth of ESCC cell lines, which was verified in xenografted mice. Ectopic PAX5 expression significantly increased p53 reporter luciferase activity and increased p53 messenger RNA and protein levels. A direct interaction of PAX5 with the p53 promoter region was confirmed by chromatin immunoprecipitation assays. Re-expression of PAX5 sensitized ESCC cell lines KYSE150 and KYSE30 to fluorouracil and docetaxel. Silencing of PAX5 induced resistance of KYSE450 cells to these drugs. CONCLUSIONS As a tumor suppressor gene regulated by promoter region methylation in human ESCC, PAX5 inhibits proliferation, promotes apoptosis, and induces activation of p53 signaling. PAX5 may serve as a chemosensitive marker of ESCC.
Animals ; Carcinoma, Squamous Cell/genetics* ; Cell Line, Tumor ; Cell Proliferation/genetics* ; Epithelial Cells/metabolism* ; Esophageal Neoplasms/genetics* ; Esophageal Squamous Cell Carcinoma/genetics* ; Gene Expression Regulation, Neoplastic ; Humans ; Mice ; PAX5 Transcription Factor/genetics* ; Tumor Suppressor Protein p53/genetics* ; Xenograft Model Antitumor Assays

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.