Two-step hard acid deprotection/cleavage procedure for solid phase peptide synthesis

A new two-step deprotection/cleavage procedure for t-butoxycarbonyl (Boc) based solid phase peptide synthesis is reported. First the protective groups are removed from 4-(oxymethyl)-phenylacetamidomethyl (PAM) resin attached peptide with the weak hard acid, trimethylsilyl bromide-thioanisole/trifluoroacetic acid (TFA). In the second step, the peptide is cleaved from the resin with a stronger hard acid such as trimethylsilvl trifluoromethanesulfonate in TFA or with HF. The method is also shown to deformylate Nⁱⁿ-formyltryptophan moiety efficiently. The usefulness of this procedure for practical solid phase peptide synthesis is demonstrated by comparison with other deprotection methods in the synthesis of urotensin II and human endothelin.     

Primary Prevention of Sudden Cardiac Death in Heart Failure: Will the Solution Be Shocking?

Sudden cardiac death (SCD) may occur in as many as 40% of all patients who suffer from heart failure. This review describes the scope of the problem, risk factors for SCD, the effect of medications used in heart failure on SCD and the potential effect of the implantable cardioverter-defibrillator in primary prevention.     

固相法合成心肌兴奋肽及其类似物

用Boc-和Tos-基团分别保护氨基和侧链胍基,以1%交联度聚苯乙烯二苯甲氨基树脂为载体,用DCC固相法合成肽,HF断裂肽树脂键和去除侧链保护基团,粗产物经高效液相层析纯化,合成了心肌兴奋肽Phe-Met-Arg-Phe-NH_2及其类似物Phe-Pro-Arg-Phe-NH_2,并观察了此二种肽对大鼠血压和心率的影响。     

乳腺癌肿瘤代谢异质性与p53基因表达和淋巴结转移相关性的研究

目的:分析乳腺癌肿瘤代谢异质性与p53基因表达和乳腺癌淋巴结转移的关系。方法:选取接受18F-FDG PET/CT检查的原发性乳腺癌患者34例,分别测定每例患者原发灶的肿瘤代谢异质因子（heterogeneity factor,HF）,同时将HF与p53基因表达和淋巴结转移进行相关性分析,采用受试者工作特性曲线（area under receiver operating characteristic curve,ROC）分析HF对p53基因突变及淋巴结转移的诊断效能。结果:HF与乳腺癌p53基因表达呈弱相关性（P<0.05）;HF与淋巴结转移无相关性（P>0.05)。结论:HF与乳腺癌p53基因表达具有相关性,HF对预测p53基因表达具有一定意义,然而,HF不能预测乳腺癌是否有淋巴结转移。     

HE4、CA125、ROMA联合应用诊断卵巢良性与恶性肿瘤的作用

目的探讨血清肿瘤标志物人附睾分泌蛋白4(HE4)、癌抗原125(CA125)和卵巢癌风险预测模型(ROMA)在卵巢癌预测和诊断的应用价值。方法回顾性分析因卵巢肿瘤住院接受手术的患者118例,健康体检女性45例,检测卵巢癌组56例和卵巢良性肿瘤组62例患者及健康女性45例血清中HE4与CA125水平;计算出ROMA值联合评估患卵巢癌的风险性。结果 HE4和CA125血清水平、ROMA值:卵巢癌组分别为(334.04±168.42)pmol/L、(424.66±188.55)U/m L,93.12%;卵巢良性肿瘤组分别为(48.24±14.20)pmol/L、(1.44±6.99)U/m L,11.56%;正常对照组分别(45.89±10.01)pmol/L、(19.14±5.01)U/m L,6.2%。卵巢癌组与良性肿瘤组、正常对照组比较,3项均有统计学差异(P0.001);良性肿瘤组与正常对照组比较,除HE4外,其它2项有统计学差异(P0.01)。HE4和CA125水平、ROMA值敏感度分别为80.6%、72.5%、85.5%,特异度分别为94.5%、76.8%、89.3%,ROC曲线线下面积(AUC)分别为0.876、0.826、0.904。结论对卵巢癌诊断,单项检查HE4临床价值优于CA125。ROMA指数表明血清CA125、HE4联合检查可以更好地预测和诊断卵巢恶性肿瘤。     

Cost-effectiveness of empagliflozin as a treatment for heart failure with reduced ejection fraction: an analysis from the Chinese healthcare perspective

BackgroundThe effect of empagliflozin on the cardiovascular outcome is consistent in heart failure with reduced ejection fraction (HFrEF) patients regardless of the presence or absence of diabetes. More evidence is needed regarding the cost-effectiveness of empagliflozin in HFrEF patients. This study sought to evaluate the economic outcomes of adding empagliflozin to the standard treatment for HFrEF patients from the perspective of the Chinese healthcare system, and thus to provide information for decision makers.MethodsBased on the EMPEROR-Reduced clinical trial and other published literature data, the direct medical costs and quality-adjusted life years (QALYs) of patients with HFrEF over a 15-year study period were simulated by a Markov model, and the incremental cost-effectiveness ratio (ICER) was calculated. The price of empagliflozin referred to the data released by Menet, the hospitalization expenses and utility values were derived from published studies in China. A one-way sensitivity analysis and probabilistic sensitivity analysis were conducted to evaluate the robustness of the model.ResultsThe results of the cost-effectiveness analysis showed that the cost of the combination arm was $5,220.98, with a utility of 4.86 QALYs, and the cost of the standard arm was $4,873.96, with a utility of 4.68 QALYs, which equated to an ICER of $1,893.59 per QALY gained. The subgroup analysis showed that patients with HFrEF and diabetes in empagliflozin group had a higher QALY (4.62 vs. 4.35) and a lower cost ($5,213.28 vs. $5,958.60) than standard group. The corresponding ICER for non-diabetic patients was $2,568.15 per QALY. Deterministic sensitivity analysis showed robust results. At the willingness-to-pay threshold of 3 times gross domestic product (GDP) per capita ($31,510.57), almost all of the scattered points in three scenarios were below the threshold line.ConclusionsAt a willingness-to-pay threshold of $31,510.57, adding empagliflozin to standard treatment is a very cost-effective option for HFrEF patients with or without diabetes in China.     

Sudomotor dysfunction is frequent and correlates with disability in Friedreich ataxia

Objectives

To evaluate autonomic symptoms and function in Friedreich’s Ataxia (FRDA).

Integrated gene expression profiling analysis reveals SERPINA3, FCN3, FREM1, MNS1 as candidate biomarkers in heart failure and their correlation with immune infiltration

BackgroundThe purpose of this study was to identify possible diagnostic indicators for heart failure (HF) and to investigate the function of immune cell infiltration in this pathophysiology.MethodsHF datasets from the Gene Expression Metascape database were utilized. R software was used to the identify differentially-expressed genes (DEGs) and perform functional correlation analysis. Least absolute shrinkage and selection operator (LASSO) and Boruta algorithms elimination algorithms were then employed to screen and validate the HF diagnostic variables. Finally, Single-sample Gene Set Enrichment Analysis (ssGSEA) was utilized to assess immune cell infiltration in HF tissues, and the Spearman association between gene expression and immune cell concentration was investigated.ResultsA total of 239 DEGs were screened in this study. SERPINA3 (area under the curve, AUC =0.958), FCN3 (AUC =0.972), FREM1 (AUC =0.954), and MNS1 (AUC =0.948) were identified as diagnostic factors of HF. The gene set differentiation analysis (GSVA) (R package “GSVA”) results showed that the high expression of FREM1 and MNS1 genes was involved in bile acid, fatty acid, and heme metabolism, suggesting that the core gene affects the progression of HF by regulating metabolism. Meanwhile, the high expression of FCN3 and SERPINA3 was related to xenobiotic metabolism, inflammatory response, and adipogenesis.ConclusionsGiven the importance of immune cell infiltration in the genesis and progression of HF, SERPINA3, FCN3, FREM1, and MNS1 may be used as diagnostic variables for HF.     

Contribution of Cardiorespiratory Fitness to the Obesity Paradox

Until recently, cardiorespiratory fitness (CRF) has been overlooked as a potential modifier of the inverse association between obesity and mortality (the so-called obesity paradox), observed in patients with known or suspected cardiovascular (CV) disease. Evidence from five observational cohort studies of 30,104 patients (87% male) with CV disease indicates that CRF significantly alters the obesity paradox. There is general agreement across studies that the obesity paradox persists among patients with low CRF, regardless of whether adiposity is assessed by body mass index, waist circumference, or percentage body fat. However, among patients with high CRF, risk of all-cause mortality is lowest for the overweight category in some, but not all, studies, suggesting that higher levels of fitness may modify the relationship between body fatness and survival in patients manifesting an obesity paradox. Further study is needed to better characterize the joint contribution of CRF and obesity on mortality in diverse populations.