Li S, et al. Diabetes Metab J. 2019 Jan;43:e28. https://doi.org/10.4093/dmj.2018.0060

Appropriately defining and using the minimal important change (MIC) and the minimal clinically important difference (MCID) are crucial for determining whether the results are clinically significant. The aim of this study is to survey the status of randomized controlled trials (RCTs) for insomnia interventions to assess the inclusion and interpretation of MIC/MCID values. We conducted a cross-sectional study to survey the status of RCTs for insomnia interventions to assess the inclusion and appropriate interpretation of MIC/MCID values. A literature search was conducted by searching the main sleep medicine journals indexed in PubMed, the Excerpta Medica Database (EMBASE), and the Cochrane Central Register of Controlled Trials (CENTRAL) to identify a broad range of search terms. We included RCTs with no restriction on the intervention. The included studies used the Insomnia Severity Index (ISI) or the Pittsburgh Sleep Quality Index (PSQI) questionnaire as the outcome measures. 81 eligible studies were identified, and more than one-third of the included studies used MIC/MCID (n = 31, 38.3%). Among them, 21 studies with ISI as the outcome used MIC defined as a relative decrease ranging from 3 to 8 points. The most frequently used MIC value was a 6-point decrease (n = 7), followed by 8-point (n = 6) and 7-point decrease (n = 4), a 4 to 5-points decrease (n = 3), and a 30% reduction from baseline; 6 studies used MCID values, ranging from 2.8 to 4 points. The most frequently used MCID value was a 4-point decrease in the ISI (n = 4). 4 studies with PSQI as the outcome used a 3-point change as the MIC (n = 2) and a 2.5 to 2.7-point difference as MCID (n = 2). 4 non-inferiority design studies considered interval estimation when drawing clinically significant conclusions in their MCID usage. The lack of consistent MIC/MCID interpretation and usage in outcome measures for insomnia highlights the urgent need for further efforts to address this issue and improve reporting practices.

Angiogenesis is crucial to facilitate tendon healing, such as delivering oxygen and nutrients, removing waste products, and controlling immune responses. Vascular endothelial growth factor (VEGF) is one of the most vital angiogenic factors that regulate blood vessel formation in tendon healing. Recently, biological therapies, including the application of exogenous VEGF, have been attracting increasing attention. However, at present, the effect of the application of exogenous VEGF in tendon healing is controversial, as the role of endogenous VEGF in tendons has also not been fully elucidated. This article will summarize the role of both endogenous and exogenous VEGF in tendon healing and discuss possible reasons for the controversy. The present review shows that tendon repair is facilitated only by proper angiogenesis and VEGF at the early stage, whereas the persistent high VEGF expression and prolonged presence of blood vessels may impair tendon repair at a later stage.

Abstract  Loss of cardiomyocytes (CMs), which lack the innate ability to regenerate, due to ageing or pathophysiological conditions (e.g. myocardial infarction or MI) is generally considered irreversible, and can lead to conditions from cardiac arrhythmias to heart failure. Human (h) pluripotent stem cells (PSCs), including embryonic stem cells (ESC) and induced pluripotent stem cells (iPSCs), can self‐renew while maintaining their pluripotency to differentiate into all cell types, including CMs. Therefore, hPSCs provide a potential unlimited ex vivo source of human CMs for disease modelling, drug discovery, cardiotoxicity screening and cell‐based heart therapies. As a fundamental property of working CMs, Ca²⁺ signalling and its role in excitation–contraction coupling are well described. However, the biology of these processes in hPSC‐CMs is just becoming understood. Here we review what is known about the immature Ca²⁺‐handling properties of hPSC‐CMs, at the levels of global transients and sparks, and the underlying molecular basis in relation to the development of various in vitro approaches to drive their maturation.

Intervertebral disc degeneration (IDD) is the leading cause of low back pain (LBP) and disability in the elderly, imposing significant public health and economic burden worldwide. Meanwhile, the pathological mechanisms of IDD remain complicated, and treatment strategy to reverse IDD is primarily due to the unclear specific mechanisms of IDD and the lack of particular effective targets. Interleukin-1β (IL-1β), one of the most important members of the IL-1 family, can induce solid pro-inflammatory activity by stimulating the secretion of various pro-inflammatory mediators and is considered the key to IDD mediator. However, in recent years, IL-1β is considered to be able to regulate IVD cell death in many ways, such as apoptosis, pyroptosis, ferroptosis, and so on. At the same time, numerous studies on IL-1β inhibitors suggest that inhibition of IL-1β may be a promising biological therapy for IDD. Many IL-1β inhibitors have been investigated through various pathogenic biological mechanisms, including inhibiting inflammatory processes, regulating ECM degradation, and more. Therefore, anti-IL-1β therapy may have the effect of alleviating disc degeneration. This article mainly reviews the mechanisms and functions of IL-1β in IDD and investigates advances in IL-1β inhibition as a promising biotherapeutic approach for disc degeneration.

Background: Previous observational studies have investigated the association between endocrine and metabolic factors and idiopathic pulmonary fibrosis (IPF), yet have produced inconsistent results. Therefore, it is imperative to employ the Mendelian randomization (MR) analysis method to conduct a more comprehensive investigation into the impact of endocrine and metabolic factors on IPF.Methods: The instrumental variables (IVs) for 53 endocrine and metabolic factors were sourced from publicly accessible genome-wide association study (GWAS) databases, with GWAS summary statistics pertaining to IPF employed as the dependent variables. Causal inference analysis encompassed the utilization of three methods: inverse-variance weighted (IVW), weighted median (WM), and MR-Egger. Sensitivity analysis incorporated the implementation of MR-PRESSO and leave-one-out techniques to identify potential pleiotropy and outliers. The presence of horizontal pleiotropy and heterogeneity was evaluated through the MR-Egger intercept and Cochran’s Q statistic, respectively.Results: The IVW method results reveal correlations between 11 traits and IPF. After correcting for multiple comparisons, seven traits remain statistically significant. These factors include: “Weight” (OR= 1.44; 95% CI: 1.16, 1.78; P=8.71×10^-4), “Body mass index (BMI)” (OR= 1.35; 95% CI: 1.13, 1.62; P=1×10^-3), “Whole body fat mass” (OR= 1.40; 95% CI: 1.14, 1.74; P=1.72×10^-3), “Waist circumference (WC)” (OR= 1.54; 95% CI: 1.16, 2.05; P=3.08×10^-3), “Trunk fat mass (TFM)” (OR=1.35; 95% CI: 1.10,1.65; P=3.45×10^-3), “Body fat percentage (BFP)” (OR= 1.55; 95% CI: 1.15,2.08; P=3.86×10^-3), “Apoliprotein B (ApoB)” (OR= 0.78; 95% CI: 0.65,0.93; P=5.47×10^-3). Additionally, the sensitivity analysis results confirmed the reliability of the MR results.Conclusion: The present study identified causal relationships between seven traits and IPF. Specifically, ApoB exhibited a negative impact on IPF, while the remaining six factors demonstrated a positive impact. These findings offer novel insights into the underlying etiopathological mechanisms associated with IPF.