沉默stathmin基因增强食管鳞癌细胞对紫杉醇敏感度的实验

目的 探讨沉默stathmin基因后,食管鳞癌细胞对紫杉醇敏感度的改变。方法 利用RNA干扰技术特异性沉默食管鳞癌KYSE150细胞的stathmin基因;实时定量PCR及蛋白质印迹法检测stathmin表达变化;CCK-8检测紫杉醇敏感度变化;流式细胞仪检测细胞周期变化;细胞分裂指数实验观察细胞有丝分裂改变。结果 特异性转染后,stathmin基因mRNA 和蛋白表达均受抑制。沉默stathmin基因后,KYSE150细胞对紫杉醇敏感度增强191.4倍;紫杉醇对特异性转染和未转染的KYSE150细胞半数抑制浓度分别为0.018 nM和3.445 nM。经紫杉醇（0.01 nM）处理72 h后,相比于未转染细胞,特异性转染的KYSE150细胞出现明显G₂/M周期阻滞[（55.4±6.2%）vs.（19.1±2.7%）, P=0.000], 有丝分裂指数减少[（5.6±0.8%）vs.（13.5±3.7%）, P=0.000]。结论 stathmin基因沉默通过细胞周期G₂/M阻滞增强食管鳞癌细胞对紫杉醇的化疗敏感度。     

Hepatoprotective activity of leaves of Cassia occidentalis against paracetamol and ethyl alcohol intoxication in rats.

Cassia occidentalis L. (Caesalpiniaceae), commonly known as 'Kasondi', is used in Unani medicine for liver ailments and is an important ingredient of several polyherbal formulations marketed for liver diseases. The hepatoprotective effect of aqueous-ethanolic extract (50%, v/v) of leaves of kasondi was studied on rat liver damage induced by paracetamol and ethyl alcohol by monitoring serum transaminase (aspartate amino transferase and serum alanine amino transferase), alkaline posphatase, serum cholesterol, serum total lipids and histopathological alterations. The extract of leaves of the plant produced significant hepatoprotection.     

Glycemic Status and Incident Heart Failure in Elderly Without History of Diabetes Mellitus: The Health, Aging, and Body Composition Study

BackgroundIt is unclear whether measures of glycemic status beyond fasting glucose (FG) levels improve incident heart failure (HF) prediction in patients without history of diabetes mellitus (DM).Methods and ResultsThe association of measures of glycemic status at baseline (including FG, oral glucose tolerance testing [OGTT], fasting insulin, hemoglobin A_1c [HbA_1c] levels, and homeostasis model assessment of insulin resistance [HOMA-IR] and insulin secretion [HOMA-B]) with incident HF, defined as hospitalization for new-onset HF, was evaluated in 2386 elderly participants without history of DM enrolled in the Health, Aging, and Body Composition Study (median age, 73 years; 47.6% men; 62.5% white, 37.5% black) using Cox models. After a median follow-up of 7.2 years, 185 (7.8%) participants developed HF. Incident HF rate was 10.7 cases per 1000 person-years with FG <100 mg/dL, 13.1 with FG 100–125 mg/dL, and 26.6 with FG ≥126 mg/dL (P = .002; P = .003 for trend). In adjusted models (for body mass index, age, history of coronary artery disease and smoking, left ventricular hypertrophy, systolic blood pressure and heart rate [HR], and creatinine and albumin levels), FG was the strongest predictor of incident HF (adjusted HR per 10 mg/dL, 1.10; 95% CI, 1.02–1.18; P = .009); the addition of OGTT, fasting insulin, HbA_1c, HOMA-IR, or HOMA-B did not improve HF prediction. Results were similar across race and gender. When only HF with left ventricular ejection fraction (LVEF) ≤40% was considered (n = 69), FG showed a strong association in adjusted models (HR per 10 mg/dL, 1.15; 95% CI, 1.03–1.29; P = .01). In comparison, when only HF with LVEF >40%, was considered (n = 71), the association was weaker (HR per 10 mg/dL, 1.05; 95% CI; 0.94–1.18; P = .41).ConclusionsFasting glucose is a strong predictor of HF risk in elderly without history of DM. Other glycemic measures provide no incremental prediction information.     

Sample size requirements for one-year treatment effects using deep gray matter volume from 3T MRI in progressive forms of multiple sclerosis

Objective: The subcortical deep gray matter (DGM) develops selective, progressive, and clinically relevant atrophy in progressive forms of multiple sclerosis (PMS). This patient population is the target of active neurotherapeutic development, requiring the availability of outcome measures. We tested a fully automated MRI analysis pipeline to assess DGM atrophy in PMS.

Design/Methods: Consistent 3D T1-weighted high-resolution 3T brain MRI was obtained over one year in 19 consecutive patients with PMS [15 secondary progressive, 4 primary progressive, 53% women, age (mean±SD) 50.8±8.0 years, Expanded Disability Status Scale (median, range) 5.0, 2.0–6.5)]. DGM segmentation applied the fully automated FSL-FIRST pipeline (http://fsl.fmrib.ox.ac.uk). Total DGM volume was the sum of the caudate, putamen, globus pallidus, and thalamus. On-study change was calculated using a random-effects linear regression model.

Results: We detected one-year decreases in raw [mean (95% confidence interval): –0.749 ml (–1.455, –0.043), p = 0.039] and annualized [–0.754 ml/year (–1.492, –0.016), p = 0.046] total DGM volumes. A treatment trial for an intervention that would show a 50% reduction in DGM brain atrophy would require a sample size of 123 patients for a single-arm study (one-year run-in followed by one-year on-treatment). For a two-arm placebo-controlled one-year study, 242 patients would be required per arm. The use of DGM fraction required more patients. The thalamus, putamen, and globus pallidus, showed smaller effect sizes in their on-study changes than the total DGM; however, for the caudate, the effect sizes were somewhat larger.

Conclusions: DGM atrophy may prove efficient as a short-term outcome for proof-of-concept neurotherapeutic trials in PMS.     

Risk factor comparison in young patients presenting with acute coronary syndrome with atherosclerotic coronary artery disease vs. angiographically normal coronaries

Background: Acute myocardial infarction is a relatively rare phenomenon in the young population. The incidence has nevertheless increased from years past, likely due to the presence of multiple risk factors from an increasingly younger age. Regardless of whether they have atherosclerotic coronary artery disease or normal coronary angiogram, young patients with risk factors for coronary artery disease (CAD), chest pain, and positive troponin, are initially treated in a similar fashion. Our goal was to shed light on whether risk factors between these two groups differ to help guide physicians in clinically determining whether or not an atherosclerotic cardiovascular event has occurred, as well as to potentially identify young patients at risk of acute coronary syndrome (ACS) despite normal coronary arteries.Methods: A retrospective cross sectional study was undertaken over an 8 year period at Tawam Hospital. 576 patients aged 50 or under who underwent coronary angiography were selected for the study. Medical records were analyzed for the patient''s demographics and CAD risk factor profile, including the following variables: family history of CAD, smoking status, Body Mass Index category, lipid profile, and diagnosis of hyperlipidemia, diabetes, or hypertension. Details of the coronary angiogram were also reviewed.Results: Statistically significant outcomes included a higher prevalence of diabetes, hyperlipidemia, and smoking history in patients with CAD compared to the patients with normal coronary angiogram. Diabetes was one of the strongest risk factors in CAD patients, with an odds ratio of 1.98 (p= 0.011), followed by hyperlipidemia at 1.85 (p= 0.021). Smoking history had an odds ratio of 2.93 (p <0.001).Conclusion: Risk factors were present in both groups, but significantly more in the CAD group. No particular risk factor stood out for the development of ACS in those with normal coronary arteries, other than mean BMI being slightly higher in this group. Based on our analysis, no single variable can accurately predict the risk for ACS in normal coronaries. To our knowledge, few studies have been done in the young population with angiographically normal coronary arteries to determine possible risk factors for development of ACS. Further research needs to be done to determine whether the risk factors that were common amongst both groups are coincidental, or a cause of ACS in those with normal coronary arteries.     

The use of negative pressure wound therapy to prevent post-operative surgical site infections following pancreaticoduodenectomy

Background

Rates of superficial surgical site infection (SSI) following pancreaticoduodenectomy remain high. Following resection for cancer, complications such as SSI impact adjuvant therapy delivery and portend worse survival. An incisional negative pressure dressing (iVAC) has been demonstrated to reduce SSI in other high-risk cohorts.