In the present study, we hypothesized that postcon (postconditioning) confers cardioprotection in vivo by reducing the production of ONOO- (peroxynitrite) and nitro-oxidative stress subsequent to the inhibition of the iNOS (inducible NO synthase). Patients with AMI (acute myocardial infarct) were randomly assigned to undergo percutaneous coronary intervention without (control) or with ischaemic postcon by three episodes of 30-s inflation and 30-s deflation of the angioplasty balloon. Animal models of MI/R (myocardial ischaemia/reperfusion) injury were induced in rats by occluding the left coronary artery for 40 min followed by 4-h reperfusion. Rats were randomized to receive vehicle, postcon (three cycles of 10-s reperfusion and 10-s coronary re-occlusion preceding full reperfusion), the selective iNOS inhibitor 1400W or postcon plus 3-morpholinosydnonimine (an ONOO- donor). Postcon in patients reduced iNOS activity in white blood cells, decreased plasma nitrotyrosine, a fingerprint of ONOO- and an index of nitro-oxidative stress, and improved cardiac function (P<0.01 compared with control). In rats, postcon reduced post-ischaemic myocardial iNOS activity and nitrotyrosine formation, reduced myocardial infarct size (all P<0.05 compared with control) and improved cardiac function. Administration of 1400W resembled, whereas 3-morpholinosydnonimine abolished, the effects of postcon. In conclusion, reduction in ONOO--induced nitro-oxidative stress subsequent to the inhibition of iNOS represents a major mechanism whereby postcon confers cardioprotection in vivo.

Ewing’s sarcoma (ES) is a highly aggressive and metastatic tumor in children and young adults caused by a chromosomal fusion between the Ewing sarcoma breakpoint region 1 (EWSR1) gene and the transcription factor FLI1 gene. ES is managed with standard treatments, including chemotherapy, surgery and radiation. Although the 5-year survival rate for primary ES has improved, the survival rate for ES patients with metastases or recurrence remains low. Several novel molecular targets in ES have recently been identified and investigated in preclinical and clinical settings, and targeting the function of receptor tyrosine kinases (RTKs), the fusion protein EWS-FLI1 and mTOR has shown promise. There has also been increasing interest in the immune responses of ES patients. Immunotherapies using T cells, NK cells, cancer vaccines and monoclonal antibodies have been considered for ES, especially for recurrent patients. Because understanding the pathogenesis of ES is extremely important for the development of novel treatments, this review focuses on the mechanisms and functions of targeted therapies and immunotherapies in ES. It is anticipated that integrating the knowledge obtained from basic research and translational and clinical studies will lead to the development of novel therapeutic strategies for the treatment of ES.

Current evidence suggests that GIK with insulin does not reduce mortality in patients with AMI. However, studies of glycaemia are inconclusive and it remains possible that glycaemic control is beneficial.

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IntroductionWith long-term follow-up, whether biodegradable polymer drug-eluting stents (DES) is efficient and safe in primary percutaneous coronary intervention (PCI) remains a controversial issue. This study aims to assess the long-term efficacy and safety of DES in PCI for ST-segment elevation myocardial infarction (STEMI).Material and methodsA prospective, randomized single-blind study with 3-year follow-up was performed to compare biodegradable polymer DES with durable polymer DES in 332 STEMI patients treated with primary PCI. The primary end point was major adverse cardiac events (MACE) at 3 years after the procedure, defined as the composite of cardiac death, recurrent infarction, and target vessel revascularization. The secondary end points included in-segment late luminal loss (LLL) and binary restenosis at 9 months and cumulative stent thrombosis (ST) event rates up to 3 years.ResultsThe rate of the primary end points and the secondary end points including major adverse cardiac events, in-segment late luminal loss, binary restenosis, and cumulative thrombotic event rates were comparable between biodegradable polymer DES and durable polymer DES in these 332 STEMI patients treated with primary PCI at 3 years.ConclusionsBiodegradable polymer DES has similar efficacy and safety profiles at 3 years compared with durable polymer DES in STEMI patients treated with primary PCI.

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Background: An increasing number of systematic reviews (SRs) and meta-analyses (MAs) of clinical trials have begun to investigate the effects of virtual reality (VR) in patients with Parkinson disease (PD). The aim of this overview of was to systematically summarize the current best evidence for the effectiveness of VR therapy for the rehabilitation of people with PD.Methods: We searched SRs/MAs based on randomized controlled trials (RCTs) for relevant literature in PubMed, Embase and Cochrane library databases from inception to December 5, 2020. The methodological quality of included SRs/MAs was evaluated with the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2), and the evidence quality of outcome measures with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Results: A total of nine SRs/MAs were included. The evaluation with AMSTAR-2 showed that all included SRs/MAs but one were rated as low or critically low quality studies. The GRADE criteria revealed 19 studies with very-low-quality evidences, 20 with low-quality evidences, 8 with moderate-quality evidences, and 1 with high-quality evidence. Effectiveness evaluation showed that VR therapy had greater improvement of stride length compared with control groups. However, there were inconsistent results (better or similar effects) regarding to gait speed, gait ability, balance, global motor function, activities of daily living, quality of life, postural control, cognitive function, and neuropsychiatric symptoms.Conclusions: VR therapy appears to be a promising and effective treatment for PD, but there is still a lack of high-quality evidence. In the future, rigorous-designed, high-quality RCTs with larger sample sizes are needed to further verify the effectiveness of VR therapy in the treatment of PD.

The objective of our overview of systematic reviews was to critically analyze the evidence from existing systematic reviews investigating the effectiveness and safety of low-level laser therapy (LLLT) in patients with breast cancer–related lymphedema (BCRL). In addition, an updated and comprehensive systematic review was conducted, which aimed to provide updated evidence about this topic. PubMed, EMBASE, and Cochrane Library databases were systematically searched for systematic reviews and randomized controlled trials (RCTs) investigating the effectiveness and safety of LLLT in patients with BCRL. The methodological quality for each of included systematic reviews or RCTs was assessed using the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR 2) tool or Cochrane risk of bias tool, respectively. The updated systematic review separately compared the effectiveness of LLLT to each of active or negative interventions. Data were pooled with random-effects models for each outcome per comparison. The evidence quality of outcomes was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) or GRADE-Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual) for quantitative studies and qualitative studies, respectively. Seven systematic reviews and ten RCTs met the eligibility criteria. Conflicting results regarding the effectiveness of LLLT were presented by the overview of systematic reviews. The AMSTAR 2 showed that the methodological quality of included systematic reviews was low or critically low quality due to one or more critical weaknesses. The GRADE and GRADE-CERQual showed that the evidence quality was low to very low for most outcomes. The updated systematic review showed that LLLT may offer additional benefits as compared to compression therapies (pneumatic compression or compression bandage), placebo laser, or no treatment for patients with BCRL. However, when compared to other types of active interventions, LLLT did not improve outcomes significantly. None of the treatment-related adverse event was reported. Many trials had a high or unclear risk of bias for two or more items, and our updated systematic review showed low quality of evidence per outcome using GRADE approach. Due to insufficient data and poor quality of evidence, there is uncertain to reach these conclusions that LLLT is superior to another active or negative intervention and is safe. More RCTs of high methodological quality, with large sample sizes and long-term follow-up, are needed to inform clinical guidelines and routine practice.