Efficacy of Huangma Ding or autologous platelet-rich gel for the diabetic lower extremity arterial disease patients with foot ulcers.

BACKGROUND: Diabetes foot is one of the most serious complications of diabetes and an important cause of death and disability, traditional treatment has poor efficacy and there is an urgent need to develop a practical treatment method. AIM: To investigate whether Huangma Ding or autologous platelet-rich gel (APG) treatment would benefit diabetic lower extremity arterial disease (LEAD) patients with foot ulcers. METHODS: A total of 155 diabetic LEAD patients with foot ulcers were enrolled and divided into three groups: Group A (62 patients; basal treatment), Group B (38 patients; basal treatment and APG), and Group C (55 patients; basal treatment and Huangma Ding). All patients underwent routine follow-up visits for six months. After follow-up, we calculated the changes in all variables from baseline and determined the differences between groups and the relationships between parameters. RESULTS: The infection status of the three groups before treatment was the same. Procalcitonin (PCT) improved after APG and Huangma Ding treatment more than after traditional treatment and was significantly greater in Group C than in Group B. Logistic regression analysis revealed that PCT was positively correlated with total amputation, primary amputation, and minor amputation rates. The ankle-brachial pressure and the transcutaneous oxygen pressure in Groups B and C were greater than those in Group A. The major amputation rate, minor amputation rate, and total amputation times in Groups B and C were lower than those in Group A. CONCLUSION: Our research indicated that diabetic foot ulcers (DFUs) lead to major amputation, minor amputation, and total amputation through local infection and poor microcirculation and macrocirculation. Huangma Ding and APG were effective attreating DFUs. The clinical efficacy of Huangma Ding was better than that of autologous platelet gel, which may be related to the better control of local infection by Huangma Ding. This finding suggested that in patients with DFUs combined with coinfection, controlling infection is as important as improving circulation.

Cell-free DNA methylation profiles enable early detection of colorectal and gastric cancer.

Colorectal cancer (CRC) and gastric cancer (GC) rank the top five common and lethal cancers worldwide. Early detection can significantly reduce the mortality of CRC and GC. However, current clinical screening methods including invasive endoscopic techniques and noninvasive fecal occult blood test screening tests/fecal immunochemical test have shown low sensitivity or unsatisfactory patient's compliance. Aberrant DNA methylation occurs frequently in tumorigenesis and cell-free DNA (cfDNA) methylation has shown the potential in multi-cancer detection. Herein, we aimed to explore the value of cfDNA methylation in the gastrointestinal cancer detection and develop a noninvasive method for CRC and GC detection. We applied targeted methylation sequencing on a total of 407 plasma samples from patients diagnosed with CRC, GC, and noncancerous gastrointestinal benign diseases (Non-Ca). By analyzing the methylation profiles of 34 CRC, 62 GC and 107 Non-Ca plasma samples in the training set (n=203), we identified 40,110 gastrointestinal cancer-specific markers and 63 tissue of origin (TOO) prediction markers. A new integrated model composed of gastrointestinal cancer detection and TOO prediction for three types of classification of CRC, GC and Non-Ca patients was further developed through logistic regression algorithm and validated in an independent validation set (n=103). The model achieved overall sensitivities of 83% and 81.3% at specificities of 81.5% and 80% for identifying gastrointestinal cancers in the test set and validation set, respectively. The detection sensitivities for GC and CRC were respectively 81.4% and 83.3% in the cohort of the test and validation sets. Among these true positive cancer samples, further TOO prediction showed accuracies of 95.8% and 95.8% for GC patients and accuracies of 86.7% and 93.3% for CRC patients, in test set and validation set, respectively. Collectively, we have identified novel cfDNA methylation biomarkers for CRC and GC detection and shown the promising potential of cfDNA as a noninvasive gastrointestinal cancer detection tool.

Improving insulin self-injection accuracy in patients with diabetes mellitus through a nursing project.

BACKGROUND: Non-standardized insulin injection has an impact on the efficacy of glucose control. OBJECTIVES: The aim of the study was to explore the effectiveness of a nursing project in improving the insulin self-injection accuracy of diabetes mellitus patients. MATERIAL AND METHODS: A total of 200 type 2 diabetes patients who received insulin therapy with an insulin pen were recruited at the First Affiliated Hospital of Army Medical University (Chongqing, China). Patients were randomly assigned to a control (n = 100) or intervention (n = 100) group. Conventional health education was conducted in the control group, while a nursing project and conventional health education were undertaken in the intervention group. The following parameters were analyzed between the 2 groups: standardized insulin pen use at admission and discharge, glycosylated hemoglobin (HbA1c), time in range (TIR), and adipose hyperplasia incidence rate 6 months after discharge. RESULTS: Concerning standardized insulin self-injection, the intervention group was superior to the control group, and the difference between the 2 groups was statistically significant (p < 0.05). The HbA1c levels (p = 0.000), TIR (p = 0.005) and adipose hyperplasia incidence rate 6 months after discharge (p = 0.000) all improved in the intervention group compared to the control group. CONCLUSIONS: The application of the nursing project effectively improved the efficacy of glucose control in diabetes mellitus patients.

Adiponectin and metabolic cardiovascular diseases: Therapeutic opportunities and challenges.

Metabolic cardiovascular diseases have become a global health concern, and some of their risk factors are linked to several metabolic disorders. They are the leading causes of death in developing countries. Adipose tissues secrete a variety of adipokines that participate in regulating metabolism and various pathophysiological processes. Adiponectin is the most abundant pleiotropic adipokine and can increase insulin sensitivity, improve atherosclerosis, have anti-inflammatory properties, and exert a cardioprotective effect. Low adiponectin concentrations are correlated with myocardial infarction, coronary atherosclerotic heart disease, hypertrophy, hypertension, and other metabolic cardiovascular dysfunctions. However, the relationship between adiponectin and cardiovascular diseases is complex, and the specific mechanism of action is not fully understood. Our summary and analysis of these issues are expected to contribute to future treatment options.

Recent Advances in Biomass-Based Materials for Oil Spill Cleanup.

Oil spill on sea surfaces, which mainly produced by the oil leakage accident happened on tankers, offshore platforms, drilling rigs and wells, has bring irreversible damage to marine environments and ecosystems. Among various spill oil handling methods, using sorbents to absorb and recover spill oils is a perspective method because they are cost-effective and enable a high recovery and without secondary pollution to the ecosystem. Currently, sorbents based on biomass materials have aroused extensively attention thanks to their features of inexpensive, abundant, biodegradable, and sustainable. Herein, we comprehensively review the state-of-the-art development of biomass-based sorbents for spill oil cleanup in the recent five years. After briefly introducing the background, the basic theory and material characteristics for the separation of oil from water and the adsorption of oils is also presented. Various modification methods for biomass materials are summarized in section three. Section four discusses the recent progress of biomass as oil sorbents for oil spill cleanup, in which the emphasis is placed on the oil sorption capacity and the separation efficiency. Finally, the challenge and future development directions is outlined.

Sex Differences in Type 2 Diabetes Mellitus-Related Left Ventricular Remodeling: A Cardiovascular Magnetic Resonance Study.

Background: The purpose of this study was to evaluate the sex differences in myocardial structure, tissue characteristics, and myocardial function in type 2 diabetes mellitus (T2DM) patients. Methods: A total of 62 T2DM patients and 40 controls were prospectively recruited for the study. All the participants were scanned using cardiovascular magnetic resonance (CMR) cine and underwent native and postcontrast T1 mapping to obtain left ventricular (LV) structure, function, and tissue characteristics. The differences between the control and T2DM patients were compared in males and females, respectively. Results: For myocardial structure, T2DM was associated with a larger ratio of myocardial mass to end-diastolic volume (MVR, T2DM: 0.87 ± 0.20 vs. controls: 0.73 ± 0.14, p = 0.008) and thicker wall thickness (WT, T2DM: 6.5 ± 1.1 mm vs. controls: 5.6 ± 1.0 mm, p = 0.002) in females. For tissue characteristics, T2DM was associated with a similar T1 value, elevated extracellular volume fraction (ECV, T2DM: 27.8 ± 3.6% vs. controls: 25.1 ± 2.5%, p = 0.002), and increased extracellular matrix volume index (ECMVi, T2DM: 15.8 ± 3.8 ml/m2 vs. controls: 13.4 ± 2.7 ml/m2, p = 0.008) in males. For myocardial function, in male, compared with control, T2DM was associated with decreased peak longitudinal diastolic strain rate (PLDSR, T2DM: 0.97 ± 0.19 1/s vs. control: 1.13 ± 0.29 1/s, p = 0.030). Conclusions: There might be sex differences in myocardial remodeling induced by T2DM, including LV structural concentric remodeling in female patients and extracellular matrix remodeling and subclinical diastolic dysfunction in male patients.

Assessment of right ventricular function using cardiovascular magnetic resonance in patients with type 2 diabetes mellitus.

BACKGROUND: Accurate evaluation of right ventricular (RV) function is always difficult due to its irregular shape and movement. Many indices have been proposed to assess RV function, but none have been universally accepted. This study evaluated RV function in type 2 diabetes mellitus (T2DM) patients using long-axis strain (LAS) and other traditional indices. METHODS: Fifty-seven patients with T2DM and 39 healthy controls were prospectively enrolled. Four-chamber cardiovascular magnetic resonance (CMR) and RV short-axis cine images were obtained from all participants to measure the tricuspid annular plane systolic excursion (TAPSE), RV ejection fraction (EF), peak longitudinal strain (PLS) and four LAS indices. The inter-and intraobserver variabilities were also calculated. RESULTS: Compared with healthy controls, T2DM was associated with a decreased LAS (apex/lateral wall) (-17.4%±4.2% vs. control, -19.7%±3.7%, P=0.008) and LAS (apex/middle point) (-17.5%±4.5% vs. control, -19.5%±3.9%, P=0.026), but both groups had a similar LAS (RV/lateral wall) and LAS (RV/middle point) (all P>0.05). After adjustments for age and body mass index, a significant difference was observed only for LAS (apex/lateral wall) (P=0.028). There were no significant differences in the TAPSE, RVEF and PLS (all P>0.05). LAS (apex/lateral wall) correlated with the TAPSE (r=-0.723, P<0.001), RVEF (r=-0.270, P=0.008) and PLS (r=0.210, P=0.040). The inter- and intraobserver variability of the LAS (apex/lateral wall) were lower than the other three LAS indices. CONCLUSIONS: Compared with traditional RV function indices, such as the TAPSE, RVEF and PLS, LAS is easy to obtain and shows high repeatability. LAS (apex/lateral wall) may provide a more sensitive T2DM-related RV dysfunction index.

CT-based radiomics nomograms for preoperative prediction of diffuse-type and signet ring cell gastric cancer: a multicenter development and validation cohort.

BACKGROUND: The prevalence of diffuse-type gastric cancer (GC), especially signet ring cell carcinoma (SRCC), has shown an upward trend in the past decades. This study aimed to develop computed tomography (CT) based radiomics nomograms to distinguish diffuse-type and SRCC GC preoperatively. METHODS: A total of 693 GC patients from two centers were retrospectively analyzed and divided into training, internal validation and external validation cohorts. Radiomics features were extracted from CT images, and the Lauren radiomics model was established with a support vector machine (SVM) classifier to identify diffuse-type GC. The Lauren radiomics nomogram integrating radiomics features score (Rad-score) and clinicopathological characteristics were developed and evaluated regarding prediction ability. Further, the SRCC radiomics nomogram designed to identify SRCC from diffuse-type GC was developed and evaluated following the same procedures. RESULTS: Multivariate analysis revealed that Rad-scores was significantly associated with diffuse-type GC and SRCC (p < 0.001). The Lauren radiomics nomogram showed promising prediction performance with an area under the curve (AUC) of 0.895 (95%CI, 0.957-0.932), 0.841 (95%CI, 0.781-0.901) and 0.893 (95%CI, 0.831-0.955) in each cohort. The SRCC radiomics nomogram also showed good discrimination, with AUC of 0.905 (95%CI,0.866-0.944), 0.845 (95%CI, 0.775-0.915) and 0.918 (95%CI, 0.842-0.994) in each cohort. The radiomics nomograms showed great model fitness and clinical usefulness by calibration curve and decision curve analysis. CONCLUSION: Our CT-based radiomics nomograms had the ability to identify the diffuse-type and SRCC GC, providing a non-invasive, efficient and preoperative diagnosis method. They may help guide preoperative clinical decision-making and benefit GC patients in the future.

Effect of Metformin on Breast Density in Overweight/Obese Premenopausal Women.

BACKGROUND: This study investigated the effects of metformin on breast density in overweight/obese premenopausal women. METHODS: Overweight/obese premenopausal women (n=120) were randomly assigned to the metformin or placebo group, and all women received lifestyle interventions. The outcomes included weight, BMI, FPG, FIN, glucose, HOMA-IR, LDL-C, HDL-C, TG, TC, SBP, DBP, FSH, E, AD, and the BIRADS grade, and the incidence of breast cancer was assessed by pathological biopsy and BIRADS grade greater than 4. RESULTS: In total, 120 overweight/obese women completed the 1-year trial. Seven patients had a BIRADS grade greater than 4, including 5 patients who were biopsy positive, in the control group, and 2 patients had a BIRADS grade greater than 4, including 1 patient who was biopsy positive, in the metformin group. Compared with those in the control group, the body weight, BMI, FIN, FPG, HOMA-IR, TC, BIRADS grade and positive pathological biopsy rate in the metformin group were significantly decreased (P<0.05), while AD was significantly increased (P<0.05). The correlation analysis indicated that the BIRADS grade was significantly correlated with weight, BMI, FPG, FIN, HOMA-IR, SBP, AD and the positive pathological biopsy rate, and the positive pathological biopsy rate was significantly correlated with weight, BMI, HOMA-IR, SBP, AD and BIRADS grade. The logistic regression analysis revealed that the BIRADS grade was significantly correlated with the positive pathological biopsy rate and AD and that the positive pathological biopsy rate was significantly correlated with the BIRADS grade. CONCLUSION: As adjunctive therapy, the combination of lifestyle changes and metformin was found to be a safe strategy for improving related metabolic markers and increasing adiponectin. The BIRADS grade was significantly correlated with the positive pathological biopsy rate and AD, and the positive pathological biopsy rate was significantly correlated with the BIRADS grade.

Dendrimer-modified gold nanorods as a platform for combinational gene therapy and photothermal therapy of tumors.

BACKGROUND: The exploitation of novel nanomaterials combining diagnostic and therapeutic functionalities within one single nanoplatform is challenging for tumor theranostics. METHODS: We synthesized dendrimer-modified gold nanorods for combinational gene therapy and photothermal therapy (PTT) of colon cancer. Poly(amidoamine) dendrimers (PAMAM, G3) grafted gold nanorods were modified with GX1 peptide (a cyclic 7-mer peptide, CGNSNPKSC). The obtained Au NR@PAMAM-GX1 are proposed as a gene delivery vector to gene (FAM172A, regulates the proliferation and apoptosis of colon cancer cells) for the combination of photothermal therapy (PTT) and gene therapy of Colon cancer cells (HCT-8 cells). In addition, the CT imaging function of Au NR can provide imaging evidence for the diagnosis of colon cancer. RESULTS: The results display that Au NR@PAMAM-GX1 can specifically deliver FAM172A to cancer cells with excellent transfection efficiency. The HCT-8 cells treated with the Au NR@PAMAM-GX1/FAM172A under laser irradiation have a viability of 20.45%, which is much lower than the survival rate of other single-mode PTT treatment or single-mode gene therapy. Furthermore, animal experiment results confirm that Au NR@PAMAM-GX1/FAM172A complexes can achieve tumor thermal imaging, targeted CT imaging, PTT and gene therapy after tail vein injection. CONCLUSION: Our findings demonstrate that the synthesized Au NR@PAMAM-GX1 offer a facile platform to exert antitumor and improve the diagnostic level of tumor.

Identify Inflammatory Bowel Disease-Related Genes Based on Machine Learning.

The patients of Inflammatory bowel disease (IBD) are increasing worldwide. IBD has the characteristics of recurring and difficult to cure, and it is also one of the high-risk factors for colorectal cancer (CRC). The occurrence of IBD is closely related to genetic factors, which prompted us to identify IBD-related genes. Based on the hypothesis that similar diseases are related to similar genes, we purposed a SVM-based method to identify IBD-related genes by disease similarities and gene interactions. One hundred thirty-five diseases which have similarities with IBD and their related genes were obtained. These genes are considered as the candidates of IBD-related genes. We extracted features of each gene and implemented SVM to identify the probability that it is related to IBD. Ten-cross validation was applied to verify the effectiveness of our method. The AUC is 0.93 and AUPR is 0.97, which are the best among four methods. We prioritized the candidate genes and did case studies on top five genes.

Corrigendum to "EOLA1 Inhibits Lipopolysaccharide-Induced Vascular Cell Adhesion Molecule-1 Expression by Association with MT2A in ECV304 Cells".

[This corrects the article DOI: 10.1155/2015/301562.].

The SGLT2 inhibitor dapagliflozin attenuates the activity of ROS-NLRP3 inflammasome axis in steatohepatitis with diabetes mellitus.

BACKGROUND: Diabetes mellitus (DM) is considered as a risk factor for the progress of liver diseases. After tissue damage, there is the highest amplitude of ubiquitously sterile inflammatory response in the liver, resulting in a major clinical consequence concerning a high prevalence of steatohepatitis in DM patients. This study aimed to investigate the inhibitory efficacy of dapagliflozin (DAPA), a sodium glucose cotransporter-2 (SGLT2) inhibitor, on experimental steatohepatitis with DM. METHODS: DM-steatohepatitis model was established by dual intraperitoneal injection of streptozotocin (STZ) and feeding with the high-fat diet (HFD) in apolipoprotein E-deficient (ApoE-/-) mice (n=40). The mice were concurrently treated with DAPA (1 mg/kg/d) by gavage for 12 weeks. RESULTS: In ApoE-/- mice, dual HFD/STZ dramatically induced hepatic damage and inflammation as compared with HFD alone. DAPA treatment was effective to protect from hepatic damage and inflammation in dual HFD/STZ treated ApoE-/- mice. DAPA also significantly the probability decreased the blood glucose, hepatic lipid accumulation, liver steatosis, and fibrotic response in dual HFD/STZ treated ApoE-/- mice. Further mechanistic investigations indicated that the protection of DAPA on diabetic liver injury was associated with the suppressed production of hepatic reactive oxygen species (ROS) and malondialdehyde (MDA) and the inhibited activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. CONCLUSIONS: These data demonstrate the efficacy of DAPA for protecting liver damage, inflammation and steatosis from experimental steatohepatitis with DM, and indicate a possible involvement of the inhibited activity of ROS-NLRP3 inflammasome.

Lower limb arterial intervention or autologous platelet-rich gel treatment of diabetic lower extremity arterial disease patients with foot ulcers.

BACKGROUND: To investigate whether lower limb vascular intervention or autologous platelet-rich gel (APG) treatment would benefit diabetic lower extremity arterial disease (LEAD) patients with foot ulcers. METHODS: A total of 82 diabetic LEAD patients with foot ulcers were recruited and divided into three groups: group A (30 patients received basal treatment), group B (21 patients received basal and APG treatment), and group C (31 patients received basal and lower limb vascular intervention treatment). All patients underwent routine follow-up visits for 6 months. The baseline characteristics and parameters were examined. After treatment, changes in all parameters from baseline were recorded. The differences between groups and the relationship among each parameter were determined. RESULTS: There were no differences in the ankle brachial index (ABI) or major amputation between groups A and B (P>0.05). Compared with groups A and B, the ABI and major amputation rate of group C were improved (P<0.05). There were no significant differences in transcutaneous oxygen partial pressure (TcPO2), the heal rate or minor amputation between groups A and C (P>0.05). Compared with groups A and C, TcPO2, the heal rate and minor amputation of group B were improved (P<0.05). The logistic regression analysis indicated that major amputation was mainly associated with the ABI, and minor amputation was mainly associated with TcPO2. Lower limb vascular intervention improves the ABI and reduces major amputation, and APG improves TcPO2 and reduces minor amputation. CONCLUSIONS: In diabetic LEAD patients with foot ulcers, major amputation was mainly associated with the ABI, while minor amputation was mainly associated with TcPO2. Interventional surgery (angioplasty) mainly improves the ABI, reduces the incidence of major amputation and improves the macrovasculature, and APG mainly improves local TcPO2, reduces the incidence of minor amputation and improves the microcirculation.

Exenatide reduces cardiomyocyte apoptosis by stimulating adiponectin secretion and activating APPL1-AMPK-PPARα axis.

BACKGROUND: To explore the mechanism that exenatide reduces cardiomyocyte apoptosis via the adiponectin pathway in vitro. METHODS: Cardiomyocytes were randomly divided into the control group (group C), diabetic group (group D), diabetic + exenatide treatment group (group DE), diabetic + exenatide treatment + APPL1 overexpression group (group OE), and diabetic + exenatide treatment + APPL1 knock-down group (group KD). After 48 h culture, the apoptosis rate, the adiponectin level in the cell culture fluid, and the expression levels of APPL1, p-AMPK, PPARα and NF-κB were detected by TUNEL, ELISA, and Western blotting, respectively. RESULTS: Compared to group C, the apoptosis rate was markedly increased, the adiponectin level was decreased, the expression of APPL1, p-AMPK and PPARα was down-regulated and that of NF-κB was up-regulated in group D (P<0.05); in group DE, the apoptosis rate was significantly decreased, the expression of APPL1, p-AMPK and PPARα was up-regulated and that of NF-κB was down-regulated, as compared with group D (P<0.05). The apoptosis rate in group OE was lower than that in group DE, the expression of APPL1, p-AMPK and PPARα was up-regulated and that of NF-κB was down-regulated (P<0.05). In group KD, the adiponectin level was elevated and the cardiomyocyte apoptosis rate was increased, as compared to group D (P<0.05). Furthermore, the expression of APPL1, p-AMPK and PPARα was down-regulated and that of NF-κB was up-regulated compared with group DE (P<0.05). CONCLUSIONS: Exenatide can activate the "APPL1-AMPK-PPARα" anti-apoptosis signaling axis by promoting adiponectin expression in cardiomyocytes and reducing the apoptosis of diabetic cardiomyocytes, thus protecting cardiomyocytes.

The Reduced Expression of EOLA1 May Be Related to Refractory Diabetic Foot Ulcer.

BACKGROUND: Chronic diabetic foot ulcer (DFU) is one of the most intractable complications of diabetes mellitus (DM). Its pathogenesis is complex, and uncontrolled chronic inflammation is an important factor. Endothelial overexpressed lipopolysaccharide-associated factor 1 (EOLA1) discovered in our laboratory is an intracellular protein with the function of inflammatory regulation. This study was aimed at observing the expression of EOLA1 in DFU skin tissues and its relationship with inflammation and at exploring the possible role of EOLA1 in DFU and its mechanism. METHODS: The patients with DFU were divided into 2 groups based on the formation time of ulcer: the acute wound (AW) group with the course of disease ≤ 4 weeks and the chronic wound (CW) group with the course of disease > 4 weeks. The relevant clinical data of patients were collected, and the skin tissues around the ulcer were used for immunofluorescence detection and immunohistochemical staining to observe inflammation. The expression levels of EOLA1, metallothionein 2A (MT2A), nuclear factor-κB (NF-κB), and interleukin-6 (IL-6) were detected by western blot. RESULTS: A total of 79 patients were enrolled in the study. The results of immunofluorescence and immunohistochemistry showed that EOLA1 was expressed in the epithelial tissues of DFU. However, the expression of EOLA1 in the CW group was significantly lower than that in the AW group (P < 0.05), and the expression of NF-κB and IL-6 was obviously increased (P < 0.05). CONCLUSION: The refractory wounds in patients with DFU may be closely related to the uncontrolled activation of inflammatory pathways in cells caused by the reduced expression of negative regulators of inflammation (e.g., EOLA1), and such decreased expression may be also strongly linked to the persistent state of inflammation.

Increased fractal dimension of left ventricular trabeculations is associated with subclinical diastolic dysfunction in patients with type-2 diabetes mellitus.

The aim of this study was to investigate the relationship among left ventricular (LV) concentric hypertrophy, endocardial remodeling, and myocardial deformation in type-2 diabetes mellitus (T2DM). Fifty-three T2DM patients with normotension and 36 healthy controls underwent cardiovascular magnetic resonance imaging to assess for LV concentric hypertrophy (LV myocardial mass index, LVMMi; LVMMi-to-LV end-diastolic volume index ratio, MVR), endocardial remodeling (fractal dimension of trabeculations, FD), and myocardial deformation (global longitudinal, radial and circumferential strain, systolic and diastolic strain rate). When compared with healthy controls, T2DM was associated with LV concentric hypertrophy (LVMMi: T2DM, 52.7 ± 8.9 g/m2; controls, 48.7 ± 8.4 g/m2, p = 0.032; MVR: T2DM, 0.88 ± 0.19 g/mL; controls, 0.77 ± 0.16 g/mL, p = 0.007), endocardial remodeling (max. apical FD: T2DM, 1.265 ± 0.056; controls, 1.233 ± 0.055, p = 0.008; mean apical FD: T2DM, 1.198 ± 0.043; controls, 1.176 ± 0.043, p = 0.020), and subtle diastolic dysfunction (peak longitudinal diastolic strain rate, PDSRL: T2DM, 1.1 ± 0.2/s; controls, 1.2 ± 0.3/s, p = 0.031). In the stepwise multivariable regression model, the MVR was an independent determinant of the maximum apical FD (standardized ß, sß = 0.525, p < 0.001) and mean apical FD (sß = 0.568, p < 0.001). The mean apical FD was an independent determinant of the PDSRL (p = 0.004). LV concentric hypertrophy is an independent determinant of endocardial remodeling, a process that may contribute to subtle LV diastolic dysfunction in T2DM patients.

ß-Catenin phosphorylation at Y654 and Y142 is crucial for high mobility group box-1 protein-induced pulmonary vascular hyperpermeability.

OBJECTIVE: Endothelial hyperpermeability is a hallmark of acute lung injury in response to sepsis. The imbalance between adherence junction (AJ) mediated cell-cell adherence forces and stress fiber driven contractile forces contributes to increased endothelial permeability. Here, we spotlight the effects of ß-catenin Y654 andY142 phosphorylation on HMGB1-mediated endothelial barrier leakage. APPROACH AND RESULTS: Our results showed that phospho-deficiencies at both ß-catenin Y654and Y142ameliorated pulmonary vascular dysfunction in male C57 mice receiving a cecal ligation and puncture operation. In vitro analysis indicated that high mobility group box-1 protein (HMGB1) triggered ß-catenin Y654 and Y142 phosphorylation, causing ß-catenin translocation and adherence junction (AJ) disruptions as well as cytoskeleton rearrangement. In addition,ß-catenin Y654 dephosphorylation attenuated HMGB1-mediated dissociation of VE-cadherin/ß-catenin and, hence, partially prevented endothelial hyperpermeability. ß-catenin Y142 dephosphorylation abolished HMGB1-induced uncoupling of ß-catenin and α-catenin, suppressed cytoskeletal reassembly and, hence, alleviated endothelial hyperpermeability. Further investigation demonstrated that RAGE and Src were required forß-catenin Y654 phosphorylation in response to HMGB1, while FAK was responsible for HMGB1-triggered ß-catenin Y142 phosphorylation. CONCLUSIONS: In sum, this study revealed the role of ß-catenin Y654 and Y142 phosphorylation in HMGB1-mediated endothelial hyperpermeability through dysregulation between adherence and contractile forces. This result advances understanding of the mechanisms underlying pulmonary vascular hyperpermeability in sepsis.

Autologous platelet-rich gel combined with in vitro amplification of bone marrow mesenchymal stem cell transplantation to treat the diabetic foot ulcer: a case report.

The diabetic foot ulcer (DFU) is the leading cause of the high mortality and morbidity rates of diabetes patients, and the DFU accounts for approximately 15% of all diagnosed diabetes cases in China. Traditional treatment is typically ineffective for DFUs. Here, we present a case of DFU that was successfully treated with an autologous platelet-rich gel (APG) and in vitro amplification of bone marrow mesenchymal stem cell (BMMSC) transplantation. A 54-year-old woman initially presented with a right foot diabetic ulcer at the hospital. A wound at the lateral malleolus of the right foot was observed with exudation and infection. The standard treatment included glucose reduction with insulin, blood lipid control with atorvastatin, circulation improvement with alprostadil, anti-infection treatment with sensitive antibiotics, debridement, dressing, and continuous negative pressure suction, and after the standard treatment, the APG combined with in vitro amplification of BMMSC transplantation was used to help the healing of the ulcer. All of the above interventions may have contributed to the healing of the ulcer, and an APG combined with in vitro amplification of BMMSCs may promote DFU healing. The difficulty of DFU treatment remains a challenge, particularly in diabetic patients who develop foot ulcers, due to the complexity of its multifaceted pathogenesis. This case represents an effective adjuvant treatment for such patients.

Distribution of Microbes and Drug Susceptibility in Patients with Diabetic Foot Infections in Southwest China.

OBJECTIVE: To investigate the microbial distribution and drug susceptibility among diabetic foot ulcers (DFUs) with different Wagner grades and between acute and chronic DFUs. Methods. We enrolled 428 DFU patients who were hospitalized and treated in the Southwest Hospital. We collected deep ulcer secretion for microbial culture and drug susceptibility tests and analyzed the results. We reexamined 67 patients with poor anti-infection efficacy and analyzed microbial species. Results: The 354 positive samples included 201 cases (56.8%) of single-pathogen infections and 153 cases (43.2%) of multiple-pathogen infections before antibiotic therapy. A total of 555 strains were cultivated, including 205 (36.9%) strains of gram-positive organisms (GPOs), 283 (51.0%) gram-negative bacilli (GNB), and 67 (12.1%) fungal strains. In terms of distribution, patients with different Wagner grades had different bacterial composition ratios (P < 0.01). Patients with Wagner grades 3-5 mainly had GNB. The specimens from chronic ulcer wounds were primarily GNB (54.2%), whereas fungi accounted for 14.4% of the infections; the distribution was significantly different from that of acute ulcers (P < 0.01). The susceptibility tests showed that the Staphylococcus genus was more susceptible to vancomycin, linezolid, and tigecycline. Tobramycin was the most effective drug (97%) for the treatment of Escherichia coli, followed by ertapenem (96.4%), imipenem (93.5%), and cefotetan (90%). Most of the remaining GNB were susceptible to antibiotics such as carbapenems, aminoglycosides, fluoroquinolones, ceftazidime, cefepime, and piperacillin-tazobactam (>63.2%). After antibiotic therapy, the positive rate of microbial culture was 52.2%, and the proportion of GNB and fungi increased to 68.9% and 20%. CONCLUSION: The distribution and types of bacteria in diabetic foot infection (DFI) patients varied with the different Wagner classification grades, courses of the ulcers, and antibiotic therapy. Multidrug resistance were increased, and the clinical treatment of DFIs should select the most suitable antibiotics based on the pathogen culture and drug susceptibility test results.