长链非编码RNA与帕金森相关性的研究进展

帕金森（Parkinson’s disease,PD）作为全球第二大神经系统退行性疾病,多发于老人,随着全球人口老龄化加剧,其发病率亦逐年上升;长链非编码 RNA（Long non-coding RNA,LncRNA）主要通过转录水平、转录后水平和表观遗传水平参与基因表达调控。越来越多研究表明,LncRNA与PD的发生发展有着密切关系。本文主要对LncRNA AS Uchl1、AS MAPT、H19、p21、Malat1、Snhg1、HOTAIR、AS PINK等对PD相关基因的表达调控进行综述,为PD的诊断、治疗和预后提供新的思路。     

Growth differentiation factor-15 in Takotsubo cardiomyopathy: Diagnostic and prognostic value

Background

Growth differentiation factor-15 (GDF-15), a stress responsive cytokine, has emerged as a marker of adverse outcome in various cardiovascular diseases. Since GDF-15 has not been evaluated in patients with Takotsubo cardiomyopathy (TTC), the present study sought to investigate the diagnostic and prognostic value in this patient cohort.

Methods

A total of 22 patients presenting with TTC were matched for age and gender with 22 ST-segment elevation myocardial infarction (STEMI) patients. GDF-15 concentrations were measured at admission and 1 day thereafter. The primary clinical endpoint of the TTC cohort was the composite of death, cardiogenic shock, or new congestive heart failure within 6 months.

Results

TTC patients showed significantly higher GDF-15 values on admission compared to patients presenting with STEMI (median 3047 ng/l [interquartile range 2256–7572] versus median 1527 ng/l [interquartile range 1152–2677]; p = 0.002). TTC patients with a biventricular ballooning pattern and patients experiencing major adverse cardiac events during the first 6 months after acute presentation showed significantly higher GDF-15 concentrations on admission (p = 0.008 and p = 0.005, respectively). Biventricular ballooning was identified as a predictor for elevated GDF-15 values on admission (p = 0.03). High GDF-15 levels on admission were the only significant predictor for the combined clinical endpoint in multivariable regression analysis (p = 0.02).

Conclusion

TTC patients showed markedly high, but transient elevation of GDF-15 levels. Biventricular ballooning was associated with particularly high GDF-15 concentrations. Elevated GDF-15 values on admission were a strong predictor of adverse clinical outcome.     

长链非编码RNA相关中药作用机制研究进展

中药是我国医药文化的瑰宝,有数千年的应用历史。然而,中药的作用机制尚未完全阐明,这在一定程度上限制了其临床应用。非编码RNA （nocoding RNA,ncRNA）是一类不能编码蛋白的转录体。几类ncRNA已被证实对疾病的发生和发展具有重要的调控作用,包括微小RNA、长链非编码RNA和环状RNA等。近年来,长链非编码RNA相关中药作用机制已成为研究热点。本文综述该领域研究进展,以期为中医药研究提供新思路。     

An indirect treatment comparison of the efficacy of patisiran and tafamidis for the treatment of hereditary transthyretin-mediated amyloidosis with polyneuropathy

Background: Hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) is a progressive, life-threatening disease. Until recently, tafamidis was the only approved pharmacotherapy. Patisiran significantly improved polyneuropathy and quality of life (QoL) in the phase III APOLLO trial. In the absence of direct comparisons, this analysis aimed to evaluate the comparative efficacy of tafamidis and patisiran in hATTR amyloidosis with polyneuropathy.

Research design and methods: Randomized controlled trial evidence for tafamidis was identified by systematic literature review. Indirect treatment comparisons were performed using the standard pairwise Bucher method for endpoints used in both APOLLO and the tafamidis Fx-005 trial: change from baseline in Neuropathy Impairment Score-lower limbs (NIS-LL), Norfolk QoL-Diabetic Neuropathy questionnaire (QoL-DN), NIS-LL response, and mBMI vs. placebo. Inter-trial population differences were assessed by sensitivity analysis.

Results: The base-case analysis (FAP Stage 1 APOLLO patients vs. intent-to-treat Fx-005 population) suggested patisiran had a greater treatment effect vs. tafamidis for all endpoints, with significant improvements in mean change in NIS-LL (–5.49) and QoL-DN (–13.10) from baseline to Month 18. Similar trends were observed in all sensitivity analyses.

Conclusions: In the absence of direct comparisons, this analysis suggests patisiran has a greater treatment effect than tafamidis in patients with hATTR amyloidosis with polyneuropathy.     

Can transient elastography,Fib-4, Forns Index,and Lok Score predict esophageal varices in HCV-related cirrhotic patients?

Background

Gastroesophageal varices are present in approximately 50% of patients with liver cirrhosis. The aim of this study was to evaluate liver stiffness measurement (LSM), Fib-4, Forns Index and Lok Score as noninvasive predictors of esophageal varices (EV).

Methods

This prospective study included 65 patients with HCV-related liver cirrhosis. All patients underwent routine laboratory tests, transient elastograhy (TE) and esophagogastroduodenoscopy. FIB-4, Forns Index and Lok Score were calculated. The diagnostic performances of these methods were assessed using sensitivity, specificity, positive predictive value, negative predictive value, accuracy and receiver operating characteristic curves.

Results

All predictors (LSM, FIB-4, Forns Index and Lok Score) demonstrated statistically significant correlation with the presence and the grade of EV. TE could diagnose EV at a cutoff value of 18.2 kPa. Fib-4, Forns Index, and Lok Score could diagnose EV at cutoff values of 2.8, 6.61 and 0.63, respectively. For prediction of large varices (grade 2, 3), LSM showed the highest accuracy (80%) with a cutoff of 22.4 kPa and AUROC of 0.801. Its sensitivity was 84%, specificity 72%, PPV 84% and NPV 72%. The diagnostic accuracies of FIB-4, Forns Index and Lok Score were 70%, 70% and76%, respectively, at cutoffs of 3.3, 6.9 and 0.7, respectively. For diagnosis of large esophageal varices, adding TE to each of the other diagnostic indices (serum fibrosis scores) increased their sensitivities with little decrease in their specificities. Moreover, this combination decreased the LR− in all tests.

Conclusion

Noninvasive predictors can restrict endoscopic screening. This is very important as non invasiveness is now a major goal in hepatology.     

High-content analysis for mitophagy response to nanoparticles: A potential sensitive biomarker for nanosafety assessment

Mitophagy, a selective autophagy of mitochondria, clears up damaged mitochondria to maintain cell homeostasis. We performed high-content analysis (HCA) to detect the increase of PINK1, an essential protein controlling mitophagy, in hepatic cells treated with several nanoparticles (NPs). PINK1 immunofluorescence-based HCA was more sensitive than assays and detections for cell viability and mitochondrial functions. Of which, superparamagnetic iron oxide (SPIO)-NPs or graphene oxide-quantum dots (GO-QDs) was selected as representatives for positive or negative inducer of mitophagy. SPIO-NPs, but not GO-QDs, activated PINK1-dependent mitophagy as demonstrated by recruitment of PARKIN to mitochondria and degradation of injured mitochondria. SPIO-NPs caused the loss of mitochondrial membrane potential, decrease in ATP, and increase in mitochondrial reactive oxide species and Ca²⁺. Blocking mitophagy with PARKIN siRNA aggravated the cytotoxicity of SPIO-NPs. Taken together, PINK1 immunofluorescence-based HCA is considered to be an early, sensitive, and reliable approach to evaluate the bioimpacts of NPs.