The transcriptional repressor RE1 silencer transcription factor(NRSF/REST) is an important factor that restricts some neuronal traits in neurons.Since these traits are also present in pancreatic islet cells,NRSF-regulated genes involved in islet function are searched.A NRSE-like motif was analysed in human insulin promoter.The role of NRSE was evaluated by generating a model of insulin-secreting cells that firmly express NRSF.The presence of NRSF led to a decrease in activity of human insulin promoter by stable or transient transfection with human insulin-promoter luciferase.The predicted NRSE-like motif also confers NRSF-dependent transcriptional repression in the context of a surrogate gene promoter.Specific binding activity of NRSF/REST to the NRSE-like motif was confirmed by EMSA.Moreover,the binding activity is competed by consensus NRSE sequence.These data showed that human insulin promoter is regulated by the transcriptional repressor NRSF/REST via the NRSE-like motif.

Objective:To explore a better indicator that can predict septic shock induced acute kidney injury (AKI) by combining renal resistive index (RRI) and central venous pressure (CVP).Methods:A prospective observational study was conducted. Patients with septic shock admitted to department of critical care medicine of Hebei General Hospital from November 2017 to October 2018 were enrolled. Baseline characteristics such as age, gender, underlying diseases, infection sites, acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) in the first 24-hour, sequential organ failure assessment (SOFA) were recorded; Doppler-based RRI was obtained on the first day when hemodynamics was relatively stable, meanwhile the dose of norepinephrine and hemodynamic parameters were assessed. Urine output per hour, the total duration of mechanical ventilation, the length of intensive care unit (ICU) stay and 28-day mortality were also collected. Observational end point was death at discharge or the 28th day after ICU admission, whenever which came first. The patients were divided into AKI and non-AKI groups according to the 2012 Kidney Disease: Improving Global Organization (KDIGO) clinical practice guideline. The baseline and prognostic indicators, variables potentially associated with AKI were compared between the two groups. The variables independently associated with septic shock induced AKI were identified using multivariable Logistic regression. The predictive value of RRI and RRI combining CVP for AKI were analyzed by the receiver operating characteristic (ROC) curve.Results:A total of 107 patients were enrolled, with 59 patients in AKI group and 48 patients in non-AKI group. There was significant difference in RRI, CVP, percentage of norepinephrine dosage ≥0.5 μg·kg -1·min -1, procalcitonin (PCT), lactate (Lac), and serum creatinine (SCr) between the two groups. Logistic regression analysis showed that high CVP, RRI, Lac and PCT were independent risk factors for septic shock induced AKI [CVP: odds ratio ( OR) = 1.20, 95% confidence interval (95% CI) was 1.03-1.40, P = 0.022; RRI: OR = 3.02, 95% CI was 2.64-3.48, P = 0.006; Lac: OR = 2.43, 95% CI was 1.32-4.50, P = 0.005; PCT: OR = 1.20, 95% CI was 1.05-1.38, P = 0.009]. ROC curve analysis showed that the area under ROC curve (AUC) values of CVP≥9.5 mmHg (1 mmHg = 0.133 kPa) and RRI≥0.695 for predicting septic shock induced AKI were 0.656 and 0.662 respectively. The AUC value of the combination of RRI and CVP was greater compared with either RRI or CVP alone in predicting septic shock induced AKI, which AUC value was 0.712, 95% CI was 0.615-0.809, the sensitivity was 59% and the specificity was 75%. Conclusions:High CVP and RRI were independent risk factors for septic shock induced AKI. The combination of RRI and CVP performs poorly in predicting septic shock induced AKI. Further studies are needed to describe factors influencing Doppler-based assessment of RRI, which may help clinicians to prevent AKI early.

Objective To investigate the impact of clinical factors on survival in patients receiving concurrent chemotherapy and three?dimensional radiotherapy ( 3DRT) for stage IV non?small cell lung cancer ( NSCLC) . Methods A total of 203 patients were enrolled in a prospective clincial study from 2008 to 2012, and among these patients, 178 patients were eligible for analysis of clinical factors. All patients were treated with platinum?based doublets chemotherapy, with a median number of chemotherapy cycles of 4( 2?6 cycles) and a median dose of 3DRT of 60?3 Gy (36?0?76?5 Gy).The Kaplan?Meier method was used to calculate overall survival ( OS) rates, the log?rank test was used to compare survival rates between groups, and the Cox regression model were used for multivariate analysis. Results The 1?, 2?, and 3?year overall survival rates were 56%, 16%, and 10%, respectively, and the median survival time was 13 months (95% CI=11?500?14?500). The univariate analysis showed that platelet count ≤221×109/L, neutrophil count ≤5.2×109/L, white blood cell count<7×109/L, and improvement in Karnofsky Performance Scale ( KPS) after treatment significantly prolonged OS ( P=0?000,0?022,0?003, and 0?029) , and metastasis to a single organ and hemoglobin≥120 g/L tended to prolong OS (P=0?058 and 0?075). The multivariate analysis showed that white blood cell count<7×109/L, platelet count ≤221×109/L, and improvement in KPS after treatment were beneficial to OS ( all P<0?05) . Conclusions White blood cell count and platelet count before treatment and KPS after treatment are prognostic factors for patients with stage IV NSCLC receiving concurrent chemotherapy and 3DRT. Clinical Trial Registry ClinicalTrials. gov, registration number:ChiCTRTNC10001026.

Objective To investigate the efficacy and safety of three?dimensional radiotherapy (3DRT) with concurrent chemotherapy for stage IV non?small?cell lung cancer ( NSCLC). Methods A total of 198 eligible patients from 2008 to 2012 were enrolled as subjects. With an age ranging between 18 and 80 years and a Karnofsky Performance Status ( KPS) score of 70 or more, those patients had no contraindication for radiotherapy and chemotherapy, and were newly diagnosed with stage IV NSCLC confirmed by histology or cytology, as well as limited metastatic disease (≤3 organs). Survival rates and acute toxicities in those patients were evaluated. Results The 3?year follow?up rate was 98?? 5% and the 3?year sample size was 165. The median overall survival (OS) and progression?free survival (PFS) were 13?? 0 months (95% CI,11?? 7 ?14?? 3 months) and 9?? 0 months (95% CI,7?? 7 ?10?? 3 months), respectively, while the 1?, 2?, and 3?year OS rates were 53?? 5%, 15?? 8%, and 9?? 2%, respectively. Multivariate analysis showed that a primary tumor volume smaller than 134 cm3 , a stable or increased KPS score after treatment, and a radiation dose of 63 Gy or more were independent prognostic factors for longer survival time ( P=0?? 008;P= 0?? 010;P= 0?? 014). The incidence rates of grade 3?4 neutropenia, thrombocytopenia, anemia, grade 3 radiation esophagitis, and grade 3 radiation pneumonitis were 37?? 9%, 10?? 1%, 6?? 9%, 2?? 5%, and 6?? 6%, respectively. The main cause of death was distant metastasis, and only 10% of the patients died of recurrence alone. Conclusions 3DRT with concurrent chemotherapy achieves satisfactory treatment outcomes with tolerable toxicities for stage IV NSCLC. Primary tumor volume, change in the KPS score after treatment, and radiation dose are independent prognostic factors for OS.Clinical Trial Registry Chinese Clinical Reistry,registration number:ChiCTRC10001026.