Use of autologous iliac crest graft and free anterolateral femoral skin flap in diabetic foot ulcers: a case report.

BACKGROUND: Diabetic foot has a great impact on the life of patients. Its treatment involves a multi-disciplinary and multi-direction approach, which requires not only soft tissue repair, but also bone reconstruction and functional repair. CASE PRESENTATION: A 51-year-old Chinese man with a three-year history of diabetes was diagnosed with ulcers in his left foot. We performed a successful procedure, and the different strategies we adopted helped to avoid serious complications during treatment. The patient was treated with debridement, bone cement, iliac crest graft, and anterolateral femoral skin flap, and recovered well. CONCLUSION: There is a dearth of reports pertaining to treatment of diabetic foot in patients with midfoot bone and soft tissue loss. In this report, we present an effective method that we used to reconstruct the loss of midfoot in a patient with diabetic foot, illustrating a successful therapeutic strategy for saving limbs in this complex medical condition.

Maggot debridement therapy stimulates wound healing by altering macrophage activation.

The purpose of this study is to determine the impact of maggot debridement therapy (MDT) on macrophages during the healing process of diabetic foot ulcers (DFU). The activation phenotype of macrophages during wound healing following MDT was evaluated using double staining immunohistochemistry (IHC). In addition, markers associated with macrophage activation were discovered using immunoblotting and real-time polymerase chain reaction (PCR). During the process of diabetic wound healing following MDT, the presence and over-expression of M2 macrophages were observed, while the under-expression of M1 macrophages was noted. In addition, the activation markers of macrophages exhibited a correlation with the indicated Th1/Th2 cytokines. MDT interventions have the potential to modulate macrophage activity, thereby aiding in the healing of diabetic foot wounds.

Closed or Unclosed Mesentery? A Meta-analysis of Internal Herniation After Laparoscopic Roux-en-Y Gastric Bypass.

During the laparoscopic Roux-en-Y gastric bypass procedure, closing mesentery or not was still controversial according to preexisted studies. So, the current meta-analysis aimed to compare the outcome of closure versus non-closure of mesenteric defects in laparoscopic Roux-en-Y gastric bypass. Fifteen studies were included, enrolling 53,488 patients. Based on the outcome of analysis, regarding internal hernia, Petersen space's IH, jejunal mesenteric's IH, hospital days, and reoperation, closure of the mesentery was better than non-closure. Besides, small bowel obstruction, anastomosis ulcer, stenosis, leakage, bleeding, gastrointestinal perforation, and postoperative BMI of patients show no difference between non-closure and closure.

A gene chip study suggests that miR-17-3p is associated with diabetic foot ulcers.

Background of the Study Diabetic foot ulcers (DFUs) are severe effect of diabetes. This research aimed to discover the role of micro-ribonucleic acid (miRNA) in treating DFUs involved in maggot debridement therapy (MDT) via a miRNA chip study. A miRNA chip approach was adopted. Patients with diabetes (type 1 or 2) who had at least one-foot ulcer (current or previous) were enrolled in the study. The alterations of miRNA expressions in the granulation tissue during treatment with MDT were measured. Following MDT, the increased expression of miR17-92 was verified in vivo. The miR-17-3p expression increased, and Flk-1 (vascular endothelial growth factor) expression was significantly reduced in patients with DFUs who received MDT (P < 0.01). Results from human umbilical vein endothelial cells that excrete or secrete showed consistency with in vitro findings (P < 0.001, P < 0.05). The overexpression of miR-17-3p demonstrated inhibitory activity on tube formation (P < 0.05). When DFUs were treated with MDT, it revealed that miR-17-3p had a negative regulatory effect on Flk-1.

Advances in metformin for the treatment of non-alcoholic fatty liver disease in children.

INTRODUCTION: The increased economic and social burdens for NAFLD worldwide make treating such a disease a significant public health issue. Metformin, a kind of insulin sensitizer generally used to treat type 2 diabetes, has been recently found to have efficacy on children's NAFLD in various areas such as glucolipid metabolism, intestinal bacterial metabolism, oxidative stress, and anti-inflammatory response. This article aims to provide an overview of the possible mechanisms of NAFLD in children and the potential therapeutic application of metformin. AREAS COVERED: The Cochrane Library, PubMed, Scopus, and EMBASE database was systematically searched on 12 April 2022, using the keywords metformin; non-alcoholic fatty liver disease; and children to identify similar studies. An additional search for recently published research was performed in June 2020. EXPERT OPINION: Although metformin has been proved to have an excellent therapeutic effect on children's NAFLD; we can still explore its potential impacts and mechanisms from different angles, such as combined medication. At the same time, we should also pay attention to its side effects.

Effects of dapagliflozin in the progression of atherosclerosis in patients with type 2 diabetes: a meta-analysis of randomized controlled trials.

AIMS: At present, an increasing number of studies are trying to determine whether dapagliflozin has a significant effect on the occurrence and development of atherosclerosis in patients with type 2 diabetes mellitus (T2DM), but there is no consensus. In addition, the former meta-analyses, relying on only a few previous studies and a minimal number of research indicators, have not been able to draw sufficient conclusions simultaneously. Consequently, we conducted a meta-analysis to evaluate the effectiveness of dapagliflozin in the occurrence and development of atherosclerosis in patients with T2DM. METHODS: We searched electronic databases (PubMed, Embase, Cochrane, and Scopus) and reference lists in relevant papers for articles published in 2011-2021. We selected studies that evaluated the effects of dapagliflozin on the risk factors related to the occurrence or development of atherosclerosis in patients with T2DM. A fixed or random-effect model calculated the weighted average difference of dapagliflozin on efficacy, and the factors affecting heterogeneity were determined by Meta-regression analysis. RESULTS: Twelve randomized controlled trials (18,758 patients) were incorporated in our meta-analysis. In contrast with placebo, dapagliflozin was associated with a significantly increase in high density lipoprotein-cholesterol (HDL-C) [MD = 1.39; 95% CI (0.77, 2.01); P < 0.0001], Δflow-mediated vasodilatation (ΔFMD) [MD = 1.22; 95% CI (0.38, 2.06); P = 0.005] and estimated Glomerular Filtration Rate(eGFR) [MD = 1.94; 95% CI (1.38, 2.51); P < 0.00001]. Furthermore, dapagliflozin had a tremendous advantage in controlling triglycerides (TG) in subgroups whose baseline eGFR < 83 ml/min/1.73m2 [MD = - 10.38; 95% CI (- 13.15, - 7.60); P < 0.00001], systolic blood pressure (SBP) [MD = - 2.82; 95% CI (- 3.22, - 2.42); P < 0.00001], HbA1c, BMI, body weight and waist circumference. However, dapagliflozin has an adverse effect on increasing total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C). Besides, there were no significant changes in other indicators, including adiponectin and C-peptide immunoreactivity. CONCLUSIONS: Our pooled analysis suggested that dapagliflozin has a terrifically better influence over HDL-C, ΔFMD, and eGFR, and it concurrently had a tremendous advantage in controlling TG, SBP, DBP, HbA1c, BMI, body weight, and waist circumference, but it also harms increasing TC and LDL-C. Furthermore, this study found that the effect of dapagliflozin that decreases plasma levels of TG is only apparent in subgroups of baseline eGFR < 83 ml/min/1.73m2, while the subgroup of baseline eGFR ≥ 83 ml/min/1.73m2 does not. Finally, the above results summarize that dapagliflozin could be a therapeutic option for the progression of atherosclerosis in patients with T2DM. Systematic review registration PROSPERO CRD42021278939.

Maggot treatment promotes healing of diabetic foot ulcer wounds possibly by upregulating Treg levels.

PURPOSE: Through the study of regulatory T cells (Tregs), we found a possible way to promote the healing of diabetic foot ulcers (DFUs) with maggot treatment and investigated the associated mechanism. METHODS: Immunohistochemistry was used to examinetissues from DFU patients treated with or without maggot debridement therapy (MDT). The expression of the signature Treg molecule Foxp3, interleukin-10 (IL-10), transforming growth factor-beta (TGF-ß), and interferon regulatory factor 4 (IRF-4) in patients with DFU treated with or without MDT was tested by real-time PCR (RT-PCR). CD4+ T cells from mouse spleen cells were cocultured in vitro with maggot excretions/secretions (ES), and Foxp3, IL-10, TGF-ß, and IRF-4 levels were measured by RT-PCR. RESULTS: Foxp3 expression was obviously increased in DFU patients treated using MDT but less pronounced in those treated without MDT (P < 0.05). Foxp3, IL-10, TGF-ß, and IRF-4 gene expression levels were higher in DFU patients treated with MDT than in those treated without MDT. Moreover, in vitro coculture of mouse spleen cells with ESs produced results consistent with the in vivo results (P < 0.001). CONCLUSION: MDT/ESs can obviously upregulate the Treg level and may affect DFU healing in different ways, suggesting a new direction for the future treatment of DFU.

Guidelines on multidisciplinary approaches for the prevention and management of diabetic foot disease (2020 edition).

In recent years, as living standards have continued to improve, the number of diabetes patients in China, along with the incidence of complications associated with the disease, has been increasing. Among these complications, diabetic foot disease is one of the main causes of disability and death in diabetic patients. Due to the differences in economy, culture, religion and level of medical care available across different regions, preventive and treatment methods and curative results for diabetic foot vary greatly. In multidisciplinary models built around diabetic foot, the timely assessment and diagnosis of wounds and appropriate methods of prevention and treatment with internal and external surgery are key to clinical practice for this pathology. In 2019, under the leadership of the Jiangsu Medical Association and Chinese Diabetes Society, the writing group for the Guidelines on multidisciplinary approaches for the prevention and management of diabetic foot disease (2020 edition) was established with the participation of scholars from the specialist areas of endocrinology, burn injury, vascular surgery, orthopedics, foot and ankle surgery and cardiology. Drawing lessons from diabetic foot guidelines from other countries, this guide analyses clinical practices for diabetic foot, queries the theoretical basis and grades and gives recommendations based on the characteristics of the pathology in China. This paper begins with assessments and diagnoses of diabetic foot, then describes treatments for diabetic foot in detail, and ends with protections for high-risk feet and the prevention of ulcers. This manuscript covers the disciplines of internal medicine, surgical, nursing and rehabilitation and describes a total of 50 recommendations that we hope will provide procedures and protocols for clinicians dealing with diabetic foot.

Cytokine storm intervention in the early stages of COVID-19 pneumonia.

Clinical intervention in patients with corona virus disease 2019 (COVID-19) has demonstrated a strong upregulation of cytokine production in patients who are critically ill with SARS-CoV2-induced pneumonia. In a retrospective study of 41 patients with COVID-19, most patients with SARS-CoV-2 infection developed mild symptoms, whereas some patients later developed aggravated disease symptoms, and eventually passed away because of multiple organ dysfunction syndrome (MODS), as a consequence of a severe cytokine storm. Guidelines for the diagnosis and treatment of SARS-CoV-2 infected pneumonia were first published January 30th, 2020; these guidelines recommended for the first time that cytokine monitoring should be applied in severely ill patients to reduce pneumonia related mortality. The cytokine storm observed in COVID-19 illness is also an important component of mortality in other viral diseases, including SARS, MERS and influenza. In view of the severe morbidity and mortality of COVID-19 pneumonia, we review the current understanding of treatment of human coronavirus infections from the perspective of a dysregulated cytokine and immune response.

Efficacy of vitamin D supplementation on glycemic control in type 2 diabetes patients: A meta-analysis of interventional studies.

BACKGROUND: Conflicting evidence exists on the effect of vitamin D supplementation on glucose metabolism in subjects with type 2 diabetes (T2D). Therefore, this meta-analysis focuses on the relationship between vitamin D intervention and glycaemic control in subjects with T2D. METHODS: We reviewed available randomized controlled trials (RCTs) studies from the establishment time of each database to March 31, 2018. Stata 13.0 software was used to evaluate the included literature. RESULTS: Finally, a total of 19 RCT studies involving 747 intervention subjects and 627 placebo controls were included in this meta-analysis. Meta-analysis results showed that compared with the control group, the short-term vitamin D supplementation group had a decline in hemoglobin A1c (HbA1c), insulin resistance, and insulin. The Standard Mean Difference (SMD) (95% CI [95% confidence interval]) of HbA1c, insulin resistance, and insulin were -0.17 (-0.29, -0.05), -0.75 (-0.97, -0.53), -0.57 (-0.78, -0.35), respectively with all P value <.05. But there were no significant differences in long-term follow-up vitamin D intervention. CONCLUSION: Vitamin D supplementation in T2D patients can improve HbA1c, insulin resistance, and insulin in short-term intervention, suggesting that vitamin D can be considered as a therapeutic agent along with the other treatments for T2D.

Increasing the miR-126 expression in the peripheral blood of patients with diabetic foot ulcers treated with maggot debridement therapy.

BACKGROUND: miR-126 may increase angiogenesis in patients with diabetic foot ulcers (DFUs) treated with maggot debridement therapy (MDT). METHODS: Real-time quantitative PCR was used to detect expression of miR-126 mRNA in the peripheral blood among the non-diabetic population, type 2 diabetes mellitus patients without DFU, and patients with DFUs of type 2 diabetes mellitus. The expression of miR-126 mRNA in the peripheral blood of patients with DFUs was observed before and after MDT. Finally, human umbilical vein endothelial cells (HUVEC) were utilized to explore miR-126 mRNA expression with maggot excretions/secretions (ES). RESULTS: In the patients with DFUs, the miR-126 mRNA expression level in the peripheral blood was less than that type 2 diabetes mellitus patients without DFU, and much lower than that in the non-diabetic population (P<0.001). The miR-126 expression level was significantly increased in those DFU patients treated with MDT (P<0.05). Finally, using HUVEC co-cultured with ES, we showed the ES increased miR-126 expression in vitro (P<0.001). CONCLUSION: MDT upregulates the miR-126 expression in the peripheral blood of patients with DFUs.

Maggot debridement therapy promotes diabetic foot wound healing by up-regulating endothelial cell activity.

To determine the role of maggot debridement therapy (MDT) on diabetic foot wound healing, we compared growth related factors in wounds before and after treatment. Furthermore, we utilized human umbilical vein endothelial cells (HUVECs) to explore responses to maggot excretions/secretions on markers of angiogenesis and proliferation. The results showed that there was neo-granulation and angiogenesis in diabetic foot wounds after MDT. Moreover, significant elevation in CD34 and CD68 levels was also observed in treated wounds. In vitro, ES increased HUVEC proliferation, improved tube formation, and increased expression of vascular endothelial growth factor receptor 2 in a dose dependent manner. These results demonstrate that MDT and maggot ES can promote diabetic foot wound healing by up-regulating endothelial cell activity.

Cyclophilin A as a downstream effector of PI3K/Akt signalling pathway in multiple myeloma cells.

Cyclophilin A (Cyp A), a member of the peptidyl-prolyl isomerase (PPI) family, may function as a molecular signalling switch. Comparative proteomic studies have identified Cyp A as a potential downstream target of protein kinase B (Akt). This study confirmed that Cyp A is a downstream effector of the phosphatidylinositide 3-kinase (PI3K)/Akt signalling pathway. Cyp A was highly phosphorylated in response to interleukin-6 treatment, which was consistent with the accumulation of phosphorylated Akt, suggesting that Cyp A is a phosphorylation target of Akt and downstream effector of the PI3K/Akt pathway. Cyclosporine A (CsA), a PPI inhibitor, inhibited the growth of multiple myeloma (MM) U266 cells. Moreover, CsA treatment inhibited the activation of the signal transducer and activator of transcription 3 (STAT3) in MM U266 cells. Several Cyp A mutants were generated. Mutants with mutated AKT phosphorylation sites increased the G1 phase arrest in MM U266 cells. The other mutants that mimicked the phosphorylated state of Cyp A decreased the percentage of G1 phase. These results demonstrated that the states of phosphorylation of Cyp A by Akt can influence the progress of the cell cycle in MM U266 cells and that this effect is probably mediated through the Janus-activated kinase 2/STAT3 signalling pathway.

[Changes of nuclear matrix proteins during apoptosis of human osteosarcoma MG-63 cells induced by curcumin].

Human osteosarcoma MG-63 cells were induced into apoptosis by curcumin (Cur). Its nuclear matrix proteins were selectively extracted, and subjected to two dimensional gel electrophoresis analysis. The resulted protein patterns were analyzed by Melanie software. There were 27 spots changed remarkably during the apoptosis induced by curcumin, 21 of which were identified. There were seven up-regulated proteins including DNA polymerase zeta and forteen down-regulated proteins including Prohibitin. This study suggests that the induced apoptosis of carcinoma cells is accompanied with changes of nuclear matrix proteins, and confirms the presence of some specific nuclear matrix proteins associated with carcinoma cell growth, apoptosis and the associated signal transduction pathways in induced apoptosis of carcinoma cells. It provides proofs and a new way to study the mechanisms of gene expression carcinogenesis which reveal the relationship between configuration and composition of nuclear matrix and cell apoptosis. Besides, this study provides several potential target proteins for cancer diagnosis and cancer therapy.

Alteration of nuclear matrix-intermediate filament system and differential expression of nuclear matrix proteins during human hepatocarcinoma cell differentiation.

AIM: To investigate the association between the configurational and compositional changes of nuclear matrix and the differentiation of carcinoma cells. METHODS: Cells cultured with or without 5 x 10(-3) mmol/L of hexamethylene bisacetamide (HMBA) on Nickel grids were treated by selective extraction and prepared for whole mount observation under electron microscopy. The samples were examined under transmission electron microscope. Nuclear matrix proteins were selectively extracted and subjected to subcellular proteomics study. The protein expression patterns were analyzed by PDQuest software. Spots of differentially expressed nuclear matrix proteins were excised and subjected to in situ digestion with trypsin. The peptides were analyzed by matrix-assisted laser-desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Data were submitted for database searching using Mascot tool (www.matrixscience.com). RESULTS: The nuclear matrix (NM) and intermediate filament (IF) in SMMC-7721 hepatocarcinoma cells were found relatively sparse and arranged irregularly. The nuclear lamina was non-uniform, and two kinds of filaments were not tightly connected. After induction for differentiation by HMBA, the NM-IF filaments were concentrated and distributed uniformly. The heterogeneous population of filaments, including highly branched ultrathin filaments could also be seen in the regular meshwork. The connection between the two kinds of filaments and the relatively thin, condensed and sharply demarcated lamina composed of intermediate-sized filaments was relatively fastened. Meanwhile, 21 NM proteins changed remarkably during SMMC-7721 cell differentiation. Four proteins, i.e. mutant Pyst1, hypothetical protein, nucleophosmin 1, and LBP were downregulated, whereas four other proteins, eIF6, p44 subunit, beta-tubulin, and SIN3B were upregulated with the last one, SR2/ASF found only in the differentiated SMMC-7721 cells. CONCLUSION: The induced differentiation of SMMC-7721 cells by HMBA is accompanied by the configurational changes of nuclear matrix-intermediate filament (NM-IF) system and the compositional changes of nuclear matrix protein expression. These changes may be important morphological or functional indications of the cancer cell reversion.

[Changes of nuclear matrix proteins during differentiation of human osteosarcoma MG-63 cells induced by HMBA].

Human osteosarcoma MG-63 cells were induced into differentiation by hexamethylene bisacetamide (HMBA). Its nuclear matrix proteins were selectively extracted, and subjected to two dimensional gel electrophoresis analysis. The resulted protein patterns were analyzed by Melanie software. There were 12 spots changed remarkably during the differentiation induced by HMBA, nine of which were identified. The up-regulated proteins were identified as MHC class II antigen, interferon-stimulated gene factor 3d, hypothetical protein DKFZp434M2221.1,8-hydroxy-guanine glycosylase homolog ogg1, and vimentin. The down-regulated ones were hnRNP A2/B1 and actin; and two newly expressed proteins under induction were 60S ribosomal protein L21 and ST2 protein. This study suggests that the induced differentiation of carcinoma cells is accompanied with changes of nuclear matrix proteins, and confirms the presence of some specific nuclear matrix proteins associated with carcinoma cell growth and differentiation. The changed nuclear matrix proteins are potential markers for cancer diagnosis or targets for cancer therapy.

Changes of nuclear matrix proteins following the differentiation of human osteosarcoma MG-63 cells.

Human osteosarcoma MG-63 cells were induced into differentiation by 5 mmol/L hexamethylene bisacetamide (HMBA). Their nuclear matrix proteins (NMPs) were selectively extracted and subjected to two-dimensional gel electrophoresis analysis. The results of protein patterns were analyzed by Melanie software. The spots of differentially expressed NMPs were excised and subjected to in situ digestion with trypsin. The maps of peptide mass fingerprinting were obtained by MALDI-TOF-MS analysis, and were submitted for NCBI database searches by Mascot tool. There were twelve spots changed remarkably during the differentiation induced by HMBA, nine of which were identified. The roles of the regulated proteins during the MG-63 differentiation were analyzed. This study suggests that the induced differentiation of cancer cells is accompanied by the changes of NMPs, and confirms the presence of some specific NMPs related to the cancer cell proliferation and differentiation. The changed NMPs are potential markers for cancer diagnosis or targets for cancer therapy.