Therapeutic Effectiveness of Leukocyte- and Platelet-rich Fibrin for Diabetic Foot Ulcers: A Retrospective Study.

OBJECTIVE: Diabetic foot ulcer (DFU) is one of the most serious complications of diabetes. Leukocyte- and platelet-rich fibrin (L-PRF) is a second-generation autologous platelet-rich plasma. This study aims to investigate the clinical effects of L-PRF in patients with diabetes in real clinical practice. METHODS: Patients with DFU who received L-PRF treatment and standard of care (SOC) from 2018 to 2019 in Tongji Hospital were enrolled. The clinical information including patient characteristics, wound evaluation (area, severity, infection, blood supply), SOC of DFU, and images of ulcers was retrospectively extracted and analyzed. L-PRF treatment was performed every 7±2 days until the ulcer exhibited complete epithelialization or an overall percent volume reduction (PVR) greater than 80%. Therapeutic effectiveness, including overall PVR and the overall and weekly healing rates, was evaluated. RESULTS: Totally, 26 patients with DFU were enrolled, and they had an ulcer duration of 47.0 (35.0, 72.3) days. The severity and infection of ulcers varied, as indicated by the Site, Ischemia, Neuropathy, Bacterial Infection, and Depth (SINBAD) scores of 2-6, Wagner grades of 1-4, and the Perfusion, Extent, Depth, Infection and Sensation (PEDIS) scores of 2-4. The initial ulcer volume before L-PRF treatment was 4.94 (1.50, 13.83) cm3, and the final ulcer volume was 0.35 (0.03, 1.76) cm3. The median number of L-PRF doses was 3 (2, 5). A total of 11 patients achieved complete epithelialization after the fifth week of treatment, and 19 patients achieved at least an 80% volume reduction after the seventh week. The overall wound-healing rate was 1.47 (0.63, 3.29) cm3/week, and the healing rate was faster in the first 2 weeks than in the remaining weeks. Concurrent treatment did not change the percentage of complete epithelialization or healing rate. CONCLUSION: Adding L-PRF to SOC significantly improved wound healing in patients with DFU independent of the ankle brachial index, SINBAD score, or Wagner grade, indicating that this method is appropriate for DFU treatment under different clinical conditions.

LILRB2/PirB mediates macrophage recruitment in fibrogenesis of nonalcoholic steatohepatitis.

Inhibition of immunocyte infiltration and activation has been suggested to effectively ameliorate nonalcoholic steatohepatitis (NASH). Paired immunoglobulin-like receptor B (PirB) and its human ortholog receptor, leukocyte immunoglobulin-like receptor B (LILRB2), are immune-inhibitory receptors. However, their role in NASH pathogenesis is still unclear. Here, we demonstrate that PirB/LILRB2 regulates the migration of macrophages during NASH by binding with its ligand angiopoietin-like protein 8 (ANGPTL8). Hepatocyte-specific ANGPTL8 knockout reduces MDM infiltration and resolves lipid accumulation and fibrosis progression in the livers of NASH mice. In addition, PirB-/- bone marrow (BM) chimeras abrogate ANGPTL8-induced MDM migration to the liver. And yet, PirB ectodomain protein could ameliorate NASH by sequestering ANGPTL8. Furthermore, LILRB2-ANGPTL8 binding-promoted MDM migration and inflammatory activation are also observed in human peripheral blood monocytes. Taken together, our findings reveal the role of PirB/LILRB2 in NASH pathogenesis and identify PirB/LILRB2-ANGPTL8 signaling as a potential target for the management or treatment of NASH.

Role of Peripheral Regulatory T Lymphocytes in Patients with Thyroid Associated Ophthalmopathy During Systemic Glucocorticoid Treatment: A Prospective Observational Study.

OBJECTIVE: Thyroid-associated ophthalmopathy (TAO) is an autoimmune disorder involving the orbital tissue. This study aimed to understand the role of regulatory T cells (Tregs) in TAO during 12-week systemic glucocorticoid (GC) treatment. METHODS: Thirty-two moderate-severe TAO patients with a clinical activity score (CAS) ≥3/7 or with prolonged T2 relaxation time (T2RT) on at least one side of extraocular muscle (EOM) were enrolled. The percentage of the peripheral CD4+CD25(high)CD127(-/low) Tregs was analyzed using flow cytometry before and after the GC treatment. The activity and severity of TAO, T2RT, and the clinical outcomes after the GC treatment were assessed. Their correlation with the peripheral Tregs was investigated. RESULTS: There was no significant association between the baseline Treg fraction and the activity and severity of TAO or the treatment response. A significant reduction of Tregs was observed after the GC therapy merely in patients without any clinical improvement. CONCLUSION: Treg reduction after systemic GC therapy is indicative of a poor therapeutic response. Accordingly, dynamic alterations of Tregs could help to evaluate the effectiveness of the GC treatment.

Liraglutide improves hepatic insulin resistance via the canonical Wnt signaling pathway.

Liraglutide, a modified form of glucagon­like peptide­1 (GLP­1), is used in the treatment of diabetes mellitus. However, the underlying mechanism by which liraglutide improves liver insulin resistance remains to be elucidated. The proto­oncogene Wnt (Wnt) signaling pathway has been reported to be associated with glucose and lipid metabolism. Using in vivo and in vitro models of diabetes and insulin resistance, it was investigated whether the beneficial effects of liraglutide on liver glucose metabolism are mediated by the Wnt signaling pathway. The results of the present study demonstrate that body weight, fasting blood glucose, insulin levels and the homeostasis model assessment for insulin resistance were markedly decreased in db/db mice treated with liraglutide compared with control mice. Liraglutide also improved liver morphology and reduced the accumulation of lipid droplets. Furthermore, the expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase was downregulated, whereas the expression of phosphorylated forkhead box O1, Wnt signaling pathway­associated molecules, ß­catenin, transcription factor 7­like 2 and phosphorylated glycogen synthase kinase-3ß was upregulated in the liver of mice treated with liraglutide. In the in vitro study, increased gluconeogenesis and decreased glucose uptake rates were observed in insulin resistant hepatocytes; treatment with liraglutide significantly reversed this effect. Furthermore, transfection of insulin resistant hepatocytes with ß­catenin small interfering RNA attenuated the effects of liraglutide, suggesting that liraglutide improves insulin resistance via activating the ß­catenin/Wnt signaling pathway. The results of the present study suggest a novel mechanism underlying liraglutide­mediated improvements in insulin resistance in the liver. The Wnt signaling pathway may be a potential therapeutic target for the treatment of altered hepatic physiology in insulin resistance.

Glycemic index, glycemic load, and glycemic response to pomelo in patients with type 2 diabetes.

Food intake has a great influence on blood glucose in patients with diabetes. This study was to determine the glycemic index (GI) and glycemic load (GL) of a particular pomelo named Majia pomelo and its effects on postprandial glucose (PPG) in patients with type 2 diabetes (T2D). Twenty healthy subjects and 20 T2D patients (controlled on lifestyle measures and/or metformin) were tested on 2 separate days with 50 g of glucose and 50 g equivalent of carbohydrates from Majia pomelo for GI measurement. To test effects of Majia pomelo on PPG, 19 hospitalized T2D patients (controlled on insulin therapy) were selected for a 9-day study. The dose of insulin for each patient was adjusted on the first 3 days. A total of 100 mg Majia pomelo was consumed per meal in the last 3 tested days. Blood glucose was measured to evaluate the glycemic excursions. The GIs for Majia pomelo in healthy individuals and T2D patients were 78.34±1.88 and 72.15±1.95 respectively. The value of GL was as low as 4.23 in diabetic patients with serving size of 100 g pomelo, indicting Majia pomelo as a high GI but low GL fruit. Consumption of Majia pomelo in hospitalized T2D patients did not cause significant glucose fluctuation. It was concluded that high GI pomelo can serve as a low GL fruit if it is consumed with a limited daily amount and thus can be supplied to diabetic patients. These results may mean more varieties of food choices for T2D patients.

Glycemic Index, Glycemic Load, and Glycemic Response to Pomelo in Patients with Type 2 Diabetes / 华中科技大学学报（医学）（英德文版）

Food intake has a great influence on blood glucose in patients with diabetes.This study was to determine the glycemic index (GI) and glycemic load (GL) of a particular pomelo named Majia pomelo and its effects on postprandial glucose (PPG) in patients with type 2 diabetes (T2D).Twenty healthy subjects and 20 T2D patients (controlled on lifestyle measures and/or metformin) were tested on 2 separate days with 50 g of glucose and 50 g equivalent of carbohydrates from Majia pomelo for GI measurement.To test effects of Majia pomelo on PPG,19 hospitalized T2D patients (controlled on insulin therapy) were selected for a 9-day study.The dose of insulin for each patient was adjusted on the first 3 days.A total of 100 mg Majia pomelo was consumed per meal in the last 3 tested days.Blood glucose was measured to evaluate the glycemic excursions.The GIs for Majia pomelo in healthy individuals and T2D patients were 78.34± 1.88 and 72.15±1.95 respectively.The value of GL was as low as 4.23 in diabetic patients with serving size of 100 g pomelo,indicting Majia pomelo as a high GI but low GL fruit.Consumption of Majia pomelo in hospitalized T2D patients did not cause significant glucose fluctuation.It was concluded that high GI pomelo can serve as a low GL fruit if it is consumed with a limited daily amount and thus can be supplied to diabetic patients.These results may mean more varieties of food choices for T2D patients.

A meta-analysis of salicylates for type 2 diabetes mellitus.

The aim of this study was to assess the effects and safety of salicylates on type 2 diabetes mellitus (T2DM). We searched six databases (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CBM, CNKI and VIP) for all randomized controlled trials (RCTs) and self-control studies which investigated the effects of salicylates on T2DM. We included 34 RCTs and 17 self-control studies involving 13 464 patients with T2DM. It was demonstrated that salicylates had obvious effects on several parameters for patients with T2DM. (1) Any dose of salicylates could significantly reduce HbA1c level [mean difference (MD) -0.39%; 95% CI -0.47 to -0.32] in RCTs, but only high doses of salicylates (≥3000 mg/day) could effectively reduce fasting plasma glucose (FPG) level [standardized mean difference (SMD) -1.05; 95% CI -1.47 to -0.62] for patients with T2DM in both RCTs and self-control studies. Furthermore, high doses of salicylates could also increase plasma fasting insulin level (MD 12.20 mU/L; 95% CI 3.33 to 21.07); (2) In both RCTs and self-control studies, high doses of salicylates could significantly reduce plasma triglycerides concentration. The results for RCTs were MD -0.44 mmol/L, 95% CI -0.71 to -0.18, and those for self-control studies were 227±29 mg/dL (pre-treatment) and 117±8 mg/dL (post-treatment) (P=0.009); (3) All trials which reported cardiovascular events were RCTs using low doses (<1000 mg/day) of salicylates, and it was revealed that aspirin could significantly reduce the risk of myocardial infarction (OR 0.73; 95% CI 0.57 to 0.92); (4) Two RCTs and two self-control studies with ≥3000 mg/day salicylates reported adverse effects, and the overall effects were mild, and tinnitus occurred most frequently. No evidence of gastrointestinal bleeding was found in all these studies. In conclusion, from our systematic review, the anti-diabetic effect of salicylates is in a dose-dependent manner. High doses of salicylates may have beneficial effects on reducing FPG, HbA1c level and increasing fasting insulin concentration, and may also have some positive effects on lipidemia and inflammation-associated parameters for patients with T2DM, without serious adverse effects.