Association of sedentary time and carotid atherosclerotic plaques in patients with type 2 diabetes.

BACKGROUND: Atherosclerosis is a common complication in patients with type 2 diabetes (T2DM). Multiple factors are involved in the development and progress of atherosclerosis. We evaluated the association of weekly sedentary time (WST) with carotid plaque formation. METHODS: After data cleaning, a total of 26 664 participants with T2DM from 10 National Metabolic Management Centers (MMCs) from June 2017 to April 2021 were enrolled. Self-reported lifestyle data including WST, sleeping time, smoking and drinking information, carotid artery ultrasound, and biochemical parameters were obtained. The independent association of carotid plaue with sedentary and other lifestyle behaviors was evaluated using multivariable logistic regression models, and odds ratio (OR) with 95% confidence interval (CI) were reported. Moreover, stratified analysis was conducted to demonstrate the influence of confounding factors. RESULTS: The mean (SD) age of the participants was 54.0 (11.6) years, and the median (interquartile range) WST was 35.0 (21.0, 42.0) h. Comparing with participants in the first tertile of WST, those in the second or third tertile of WST were younger and with a shorter duration of diabetes. There were positive associations between longer sedentary time and odds of artery plaque after adjustment, with corresponding ORs in the second and third tertile were 1.40 (95% CI: 1.31-1.50) and 1.67 (95% CI: 1.56-1.79), respectively. However, the effect of WST on plaque in patients aged 18-40 years old had no statistical significance; the p value in the third tertile was 0.163. CONCLUSIONS: In summary, higher WST appears to be associated with higher prevalence of carotid plaque in patients with T2DM, especially in aged populations.

Risk Factors of Postoperative Vomiting in the Eye of "Real-World Evidence"-Modifiable and Clinical Setting-Dependent Risk Factors in Surgical Trauma Patients.

Numerous studies on postoperative nausea and vomiting (PONV) have been carried out since the early days of contemporary surgery. The incidence of PONV has been greatly reduced in recent years and new drugs for PONV keep evolving in the market; however, a substantial number of patients are still under the threat of PONV. Female gender, non-smokers, a history of PONV/motion sickness, and postoperative opioid use are four well-recognized risk factors of PONV. Many potential risk factors reported in previous studies were not consistently presented as predictors for PONV. Two questions then arise; are risk factors clinical setting dependent and are risk factors modifiable? We attempted to answer the questions through a comprehensive review of perioperative records of surgical patients from the Trauma Department of our hospital. As nausea is subjective and no standard is applicable for its measurement, postoperative vomiting (POV) was used as an endpoint in this study. To the best of our knowledge, this is the first study to address the POV issue in surgical trauma patients. A total of 855 patients were enrolled in this study after excluding age below 20 years old, total intravenous anesthesia, desflurane anesthesia, or records with missing data. Our results showed that female gender (OR 4.89) is the strongest predicting factor, followed by a less potent predicting factor-more intraoperative opioid consumption (OR 1.07)-which favor more POV. More intraoperative crystalloid supply (OR 0.71) and a higher body weight (OR 0.9) favor less POV. Other potential risk factors did not reach statistical significance in this study as independent risk factors. Our results also showed that when the intraoperative crystalloid infusion rate is greater than 4 mL/kg/h (OR 0.20), it favors a lower rate of POV; when intraoperative opioid consumption is greater than 12 mg morphine equivalents, MME (OR 1.87), it favors a higher rate of POV. We concluded that dominance of any independent risk factor over other risk factors depends on how individual factors interact with the clinical setting. Some risk factors could be modified, and a cut-off value could be derived to facilitate a better plan for POV prevention.

Artificial intelligence-enabled screening for diabetic retinopathy: a real-world, multicenter and prospective study.

INTRODUCTION: Early screening for diabetic retinopathy (DR) with an efficient and scalable method is highly needed to reduce blindness, due to the growing epidemic of diabetes. The aim of the study was to validate an artificial intelligence-enabled DR screening and to investigate the prevalence of DR in adult patients with diabetes in China. RESEARCH DESIGN AND METHODS: The study was prospectively conducted at 155 diabetes centers in China. A non-mydriatic, macula-centered fundus photograph per eye was collected and graded through a deep learning (DL)-based, five-stage DR classification. Images from a randomly selected one-third of participants were used for the DL algorithm validation. RESULTS: In total, 47 269 patients (mean (SD) age, 54.29 (11.60) years) were enrolled. 15 805 randomly selected participants were reviewed by a panel of specialists for DL algorithm validation. The DR grading algorithms had a 83.3% (95% CI: 81.9% to 84.6%) sensitivity and a 92.5% (95% CI: 92.1% to 92.9%) specificity to detect referable DR. The five-stage DR classification performance (concordance: 83.0%) is comparable to the interobserver variability of specialists (concordance: 84.3%). The estimated prevalence in patients with diabetes detected by DL algorithm for any DR, referable DR and vision-threatening DR were 28.8% (95% CI: 28.4% to 29.3%), 24.4% (95% CI: 24.0% to 24.8%) and 10.8% (95% CI: 10.5% to 11.1%), respectively. The prevalence was higher in female, elderly, longer diabetes duration and higher glycated hemoglobin groups. CONCLUSION: This study performed, a nationwide, multicenter, DL-based DR screening and the results indicated the importance and feasibility of DR screening in clinical practice with this system deployed at diabetes centers. TRIAL REGISTRATION NUMBER: NCT04240652.

Ischemic Postconditioning Mitigates Retinopathy in Tree Shrews with Diabetic Cerebral Ischemia.

Ischemic postconditioning (PC) is proved to efficiently protect diabetic patients with acute myocardial infarction from ischemia-reperfusion injury. We aimed to explore the protective roles of ischemic PC on diabetic retinopathy in tree shrews with diabetic cerebral ischemia. A diabetic tree shrew model was established through high-fat diet feeding combined with streptozotocin (STZ) injection, while cortical thrombotic cerebral ischemia was induced photochemically. Tree shrews were divided into the normal control group, sham operation group, diabetes mellitus group, diabetes mellitus+cerebral ischemia group, and diabetes mellitus+cerebral ischemia+PC group (in which the tree shrews with diabetic cerebral ischemia were treated with ischemic PC). H&E staining was used to examine the pathological changes in the retina, and immunohistochemistry was performed to determine the retinal expression of VEGF (vascular endothelial growth factor). The modeling resulted in 77% tree shrews with diabetes. Ischemic PC reduced the blood glucose levels in the tree shrews with diabetic cerebral ischemia. Tree shrews with diabetes had thinned retina with disordered structures, and these pathological changes were aggravated after cerebral ischemia. The retinopathy was alleviated after ischemic PC. Retina expression of VEGF was mainly distributed in the ganglion cell layer in tree shrews. Diabetes and cerebral ischemia increased retinal VEGF expression in a step-wise manner, while additional ischemic PC reduced retinal VEGF expression. Therefore, ischemic PC effectively alleviates retinopathy in tree shrews with diabetic cerebral ischemia, and this effect is associated with reduced retinal VEGF expression.

Composite Hydrogel Modified by IGF-1C Domain Improves Stem Cell Therapy for Limb Ischemia.

Stem cell treatment for critical limb ischemia yields a limited therapeutic effect due to cell loss and dysfunction caused by local ischemic environment. Biomimetic scaffolds emerge as ideal cell delivery vehicles for regulating cell fate via mimicking the components of stem cell niche. Herein, we prepared a bioactive hydrogel by mixing chitosan and hyaluronic acid that is immobilized with C domain peptide of insulin-like growth factor 1 (IGF-1C) and examined whether this hydrogel could augment stem cell survival and therapeutic potential. Our results showed that IGF-1C-modified hydrogel increased in vitro viability and proangiogenic activity of adipose-derived stromal cells (ADSCs). Moreover, cotransplantation of hydrogel and ADSCs into ischemic hind limbs of mice effectively ameliorated blood perfusion and muscle regeneration, leading to superior limb salvage. These therapeutic effects can be ascribed to improved ADSC retention, angiopoientin-1 secretion, and neovascularization, as well as reduced inflammatory cell infiltration. Additionally, hydrogel enhanced antifibrotic activity of ADSCs, as evidenced by decreased collagen accumulation at late stage. Together, our findings indicate that composite hydrogel modified by IGF-1C could promote survival and proangiogenic capacity of ADSCs and thereby represents a feasible option for cell-based treatment for critical limb ischemia.

Co-Transplantation of Skin-Derived Precursors and Collagen Sponge Facilitates Diabetic Wound Healing by Promoting Local Vascular Regeneration.

BACKGROUND/AIMS: Impaired diabetes wound healing can often lead to serious complications and remains a major health concern due to the lack of effective therapeutic approaches. Compromised angiogenesis, disrupted growth factor and cytokine activity are all attributable to diabetic wound healing impairment. The skin-derived precursors (SKPs) have been shown to differentiate into vascular and nerve cells, both of which are crucial components for wound repair. Given their easy accessibility and multipotency, the SKPs were proposed as an ideal therapeutic candidate for diabetic wound healing. Since the efficacy of cell therapy is limited by poor cell survival, collagen sponge was employed for better SKPs delivery. METHODS: SKPs were isolated and transplanted directly to the wound areas of diabetic mice in the absence and presence of collagen sponge. The effects of SKPs and/or collagen sponge on diabetic wound healing were examined histologically as well as immunostaining of isolectin and α-SMA. Mechanisms via which the SKPs facilitate wound healing were then investigated by transplanting SKPs that have been pre-labelled with a fluorescence dye, Dil. Expression patterns of Dil and an SKP marker, nestin, was also examined. RESULTS AND CONCLUSION: Accelerated wound healing and enhanced local capillary regeneration could be observed 14 days after skin ablation from both SKPs and collagen sponge co-transplanted and collagen sponge only groups. Subsequent analyses further revealed superior pro-angiogenic effects from the SKP and collagen sponge co-delivered group, which are mainly attributable to in vivo transdifferentation and paracrine signalling of the SKPs.

Skin-derived precursor cells promote angiogenesis and stimulate proliferation of endogenous neural stem cells after cerebral infarction.

Stroke is one of the most common diseases that caused high mortality and has become burden to the health care systems. Stem cell transplantation has shown therapeutic effect in ameliorating ischemic damage after cerebral artery occlusion mainly due to their neurogenesis, immune regulation, or effects on the plasticity, proliferation, and survival of host cells. Recent studies demonstrated that skin-derived precursor cells (SKPs) could promote central nervous system regeneration in spinal cord injury model or the neonatal peripheral neuron. Here, we investigated the therapeutic potential of SKPs in a rat model of cerebral ischemia. SKPs were isolated, expanded, and transplanted into rat cortex and striatum after transient middle cerebral artery occlusion. Our results revealed that SKPs transplantation could improve the behavioral measures of neurological deficit. Moreover, immunohistology confirmed that SKPs could secrete basic FGF and VEGF in the ischemic region and further markedly increase the proliferation of endogenous nestin(+) and ßIII-tubulin(+) neural stem cells. Furthermore, increased angiogenesis induced by SKPs was observed by vWF and α-SMA staining. These data suggest that SKPs induced endogenous neurogenesis and angiogenesis and protected neuron from hypoxic-ischemic environment. In conclusion, SKPs transplantation may be a promising approach in treatment of stroke.

Netrin-1 ameliorates myocardial infarction-induced myocardial injury: mechanisms of action in rats and diabetic mice.

Netrin-1 is typically known as a neuronal guidance factor. Studies have reported the proangiogenic, antiapoptotic, and antiinflammatory properties of Netrin-1. A critical role for Netrin-1 in ischemic organ damage, myocardial infarction (MI) in particular, has also been demonstrated, making Netrin-1 a potential therapeutic target for the treatment of cardiovascular diseases (CVDs). Mesenchymal stem cells (MSCs) have shown promising therapeutic efficacy in preclinical studies. However, limited clinical success was observed, mainly due to poor MSC survival. Given the reported beneficial impact of Netrin-1 in tissue repair and cell survival, we examined the effects of Netrin-1 in MSC therapy against MI-induced ischemic cardiac injury in rats and type 2 diabetic (T2D) mice. MSCs were isolated and Netrin-1-expressing MSCs were obtained by transduction with a Netrin-1-encoding retroviral vector. The Netrin-1-MSCs were then delivered intramyocardially to the infarct sites of rats and T2D mice with MI. Thirty days after MSC implantation, changes at the infarct area, level of collagen deposition, and cardiac hypertrophy were assessed. Molecular mechanisms underlying the effects of Netrin-1 were also investigated. Attenuated MI-induced myocardial dysfunction was observed after Netrin-1-MSC treatment. Protective effects of the Netrin-1-MSCs were attributable primarily to better MSC survival and migration, which is mediated by Netrin-1-induced phosphorylation of p44/42 mitogen-activated protein kinase. Netrin-1-stimulated nitric oxide production was also responsible, which could promote neovessel formation and progenitor cell mobilization in vivo. We report a protective role for Netrin-1 against MI-induced ischemic injuries, reinstating its promising potential as a therapeutic target for CVDs and, more importantly, for patients with CVD with coexisting diabetes.