Publications by authors named "Wuquan Deng"

45 Publications

The amputation and mortality of inpatients with diabetic foot ulceration in the COVID-19 pandemic and postpandemic era: A machine learning study.

Int Wound J 2021 Nov 24. Epub 2021 Nov 24.

Department of Endocrinology, School of Medicine, Bioengineering College, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing University, Chongqing, China.

This study aimed to explore the clinical characteristic and outcomes of inpatients with diabetic foot ulceration (DFU) in 2019 (prelockdown) and 2020 (postlockdown) due to the COVID-19 pandemic, at an emergency medical service unit. Prediction models for mortality and amputation were developed to describe the risk factors using a machine learning-based approach. Hospitalized DFU patients (N = 23) were recruited after the lockdown in 2020 and matched with corresponding inpatients (N = 23) before lockdown in 2019. Six widely used machine learning models were built and internally validated using 3-fold cross-validation to predict the risk of amputation and death in DFU inpatients under the COVID-19 pandemic. Previous DF ulcers, prehospital delay, and mortality were significantly higher in 2020 compared to 2019. Diabetic foot patients in 2020 had higher hs-CRP levels (P = .037) but lower hemoglobin levels (P = .017). The extreme gradient boosting (XGBoost) performed best in all models for predicting amputation and mortality with the highest area under the curve (0.86 and 0.94), accuracy (0.80 and 0.90), sensitivity (0.67 and 1.00), and negative predictive value (0.86 and 1.00). A long delay in admission and a higher risk of mortality was observed in patients with DFU who attended the emergency center during the COVID-19 post lockdown. The XGBoost model can provide evidence-based risk information for patients with DFU regarding their amputation and mortality. The prediction models would benefit DFU patients during the COVID-19 pandemic.
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http://dx.doi.org/10.1111/iwj.13723DOI Listing
November 2021

Time in range in relation to amputation and all-cause mortality in hospitalised patients with diabetic foot ulcers.

Diabetes Metab Res Rev 2021 Sep 29:e3498. Epub 2021 Sep 29.

Department of Endocrinology, College of Medicine, College of Bioengineering, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing University, Chongqing, China.

Aims: The aim of this study was to evaluate the association of time in range (TIR) with amputation and all-cause mortality in hospitalised patients with diabetic foot ulcers (DFUs).

Materials And Methods: A retrospective analysis was performed on 303 hospitalised patients with DFUs. During hospitalisation, TIR, mean blood glucose (MBG), coefficient of variation (CV), time above range (TAR) and time below range (TBR) of patients were determined from seven-point blood glucose profiles. Participants were grouped based on their clinical outcomes (i.e., amputation and death). Logistic regression was employed to analyse the association of TIR with amputation and all-cause mortality of inpatients with DFUs.

Results: Among the 303 enrolled patients, 50 (16.5%) had undergone amputation whereas seven (2.3%) were deceased. Blood glucose was determined in 41,012 samples obtained from all participants. Patients who underwent amputation had significantly lower TIR and higher MBG, CV, level 2 TAR and level 1 TBR whereas deceased patients had significantly lower TIR and higher MBG and level 2 TAR. Both amputation and all-cause mortality rate declined with an increase in TIR quartiles. Logistic regression showed association of TIR with amputation (p = 0.034) and all-cause mortality (p = 0.013) after controlling for 15 confounders. This association was similarly significant in all-cause mortality after further adjustment for CV (p = 0.022) and level 1 TBR (p = 0.021), respectively.

Conclusions: TIR is inversely associated with amputation and all-cause mortality of hospitalised patients with DFUs. Further prospective studies are warranted to establish a causal relationship between TIR and clinical outcomes in patients with DFUs.
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http://dx.doi.org/10.1002/dmrr.3498DOI Listing
September 2021

An explainable machine learning model for predicting in-hospital amputation rate of patients with diabetic foot ulcer.

Int Wound J 2021 Sep 14. Epub 2021 Sep 14.

Department of Endocrinology and Metabolism, Chongqing Emergency Medical Center, Chongqing Key Laboratory of Emergency Medicine, Chongqing University Central Hospital, Chongqing University, Chongqing, China.

Diabetic foot ulcer (DFU) is one of the most serious and alarming diabetic complications, which often leads to high amputation rates in diabetic patients. Machine learning is a part of the field of artificial intelligence, which can automatically learn models from data and better inform clinical decision-making. We aimed to develop an accurate and explainable prediction model to estimate the risk of in-hospital amputation in patients with DFU. A total of 618 hospitalised patients with DFU were included in this study. The patients were divided into non-amputation, minor amputation or major amputation group. Light Gradient Boosting Machine (LightGBM) and 5-fold cross-validation tools were used to construct a multi-class classification model to predict the three outcomes of interest. In addition, we used the SHapley Additive exPlanations (SHAP) algorithm to interpret the predictions of the model. Our area under the receiver-operating-characteristic curve (AUC) demonstrated a 0.90, 0.85 and 0.86 predictive ability for non-amputation, minor amputation and major amputation outcomes, respectively. Taken together, our data demonstrated that the developed explainable machine learning model provided accurate estimates of the amputation rate in patients with DFU during hospitalisation. Besides, the model could inform individualised analyses of the patients' risk factors.
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http://dx.doi.org/10.1111/iwj.13691DOI Listing
September 2021

Pain Management in People with Diabetes-Related Chronic Limb-Threatening Ischemia.

J Diabetes Res 2021 8;2021:6699292. Epub 2021 May 8.

Department of Rehabilitation, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.

Management of neuropathic pain in people with diabetes has been widely investigated. However, little attention was paid to address ischemic-related pain in patients with diabetes mellitus who suffered from chronic limb-threatening ischemia (CLTI), the end stage of lower extremity arterial disease (LEAD). Pain management has a tremendous influence on patients' quality of life and prognosis. Poor management of this type of pain owing to the lack of full understanding undermines patients' physical and mental quality of life, which often results in a grim prognosis, such as depression, myocardial infarction, lower limb amputation, and even mortality. In the present article, we review the current strategy in the pain management of diabetes-related CLTI. The endovascular therapy, pharmacological therapies, and other optional methods could be selected following comprehensive assessments to mitigate ischemic-related pain, in line with our current clinical practice. It is very important for clinicians and patients to strengthen the understanding and build intervention strategy in ischemic pain management and possible adverse consequence.
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http://dx.doi.org/10.1155/2021/6699292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128546PMC
May 2021

Comparison and Investigation of Exosomes Derived from Platelet-Rich Plasma Activated by Different Agonists.

Cell Transplant 2021 Jan-Dec;30:9636897211017833

The Key Laboratory of Laboratory Medical Diagnostics in the Ministry of Education and Department of Clinical Biochemistry, College of Laboratory Medicine, 12550Chongqing Medical University, Chongqing, China.

PRP-Exos are nanoscale cup-shaped vesicles that carry a variety of proteins, mRNAs, microRNAs, and other bioactive substances. PRP-Exos can be formed through several induction pathways, which determine their molecular profiles and facilitate their tailormade participation in intercellular communication. Currently, little is known on how the PRP-Exos activation method influences the quality and quantity of PRP-Exos. The present study aims to observe and analyze the number, profile, and growth factors of PRP-Exos through TEM, Nanoflow, and WB after PRP activation and compare the difference in function of PRP-Exos on HUVECs, with different stimuli (calcium gluconate, thrombin, or both). We found that PRP activated with both thrombin and calcium gluconate harvested the highest concentration of exosomes [(7.16 ± 0.46) × 10 particles/ml], compared to thrombin group [(4.87 ± 0.15) × 10 particles/ml], calcium gluconate group [(5.85 ± 0.43) × 10 particles/ml], or saline group [(7.52 ± 0.19) × 10 particles/ml], respectively ( < 0.05) via Nanoflow analysis. The WB analysis showed that cytokines (VEGF, PDGFBB, bFGF, TGF-β) are differentially encapsulated in PRP-Exos, depending on the PRP stimulus, in which the mixture-PRP-Exos yielded the highest concentration of cytokines. In the function assay of PRP-Exos on HUVECs, the mixture-PRP-Exos promoted HUVECs proliferation, increased HUVECs migration, promoted the formation of vessel-like by HUVECs via the AKT ERK signal pathway more dramatically, compared with other groups. In summary, our studies showed that PRP activated by the mixture of calcium gluconate and thrombin harvested the best quality of exosomes which had the top biological functions. This study provides a protocol for selecting appropriate PRP activators to obtain high-quality exosomes for future applications.
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http://dx.doi.org/10.1177/09636897211017833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138303PMC
May 2021

The Relationship Between Metabolic Parameters, Age, and Thyroid Status: A Cross-Sectional Study-Based National Survey of Iodine Nutrition, Thyroid Disease.

Risk Manag Healthc Policy 2021 23;14:1723-1730. Epub 2021 Apr 23.

Department of Rehabilitation, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People's Republic of China.

Aim: The relationship between thyroid status and metabolic factors was investigated as well as iodine nutrition in the general population and among the elderly population.

Methods: We performed a cross-sectional survey of 2483 subjects to assess the status of national iodine nutrition and incidence of thyroid disease. The general and elderly populations were divided into normal thyroid function (NTF) and subclinical hypothyroidism (SCH) groups. The anthropometric parameters and biochemical indicators were then analyzed.

Results: Overall, 327 participants were diagnosed with thyroid diseases, 73 (22.32%) of whom were 65 years or older. For the general population, compared with the NTF group, individuals in the SCH group were older, presented with higher systolic blood pressure, fasting blood glucose, serum cholesterol, and urinary iodine concentration (all p<0.05) but lower blood uric acid (UA) (p<0.05). Linear regression analysis further revealed that age and triglyceride (TG) serum levels positively correlated with serum thyroid-stimulating hormone (TSH) levels. Multiple regression analyses revealed that age, TG, waist circumference (WC), and body mass index were independent predictors for abnormal TSH serum levels. For the elderly population, compared with NTF group, individuals in the SCH group were substantially older (p<0.05) but presented with lower UA (p<0.05). Pearson linear regression analysis revealed a positive correlation between age (p=0.003) as well as TG levels (p<0.001) and serum TSH levels. In contrast, WC (p=0.003) was negatively related to TSH serum levels. Further multiple regression analysis revealed that age, TG, WC and heart rate were independent predictors of blood TSH.

Conclusion: The large-scale national study of iodine nutrition, thyroid disease has shown a vital relationship between metabolic indicators and serum TSH levels. Age and metabolic diseases increase the likelihood of developing thyroid diseases, both the general population and among the elderly.
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http://dx.doi.org/10.2147/RMHP.S306122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079349PMC
April 2021

Benefits of sucrose octasulfate (TLC-NOSF) dressings in the treatment of chronic wounds: a systematic review.

J Wound Care 2021 Apr;30(Sup4):S42-S52

International Medical Director, Urgo Education and Training Alliance, Singapore.

Objective: Management of chronic wounds remains one of the major challenges for health professionals and patients. An evidence-based decision is important to ensure that patients are receiving the best treatment proven to reduce healing time and improve outcomes, including economic benefits and patients' health-related quality of life (HRQoL). Due to recent restrictions because of the COVID-19 pandemic, including closure of wound care centres within hospitals and a drop in patient volume, chronic wound management needs simple-to-use dressings which are still effective and evidence-based solutions. This systematic review was conducted to identify the clinical evidence available on a sucrose octasulfate dressing (TLC-NOSF, UrgoStart dressing range, Laboratoires Urgo, France) to explore its efficacy in the management of chronic wounds, particularly lower limb ulcers, diabetic foot ulcers and pressure ulcers.

Method: A literature search of PubMed, Cochrane Library and Google Scholar was conducted based on the PICO model (patient/population, intervention, comparison and outcomes) to retrieve publications of different levels of evidence in order to evaluate outcomes of the use of TLC-NOSF dressings.

Results: A total of 21 publications of different levels, ranging from double-blind randomised control trials to case reports, involving over 12,000 patients, were identified through PubMed, with a further eight publications through Google Scholar and two publications through Cochrane Library. A total of seven results were omitted due to the lack of relevance or repetition.

Conclusion: All the evidence provided suggest that these dressings provide clinicians with an evidence-based option for the management of chronic wounds; that the TLC-NOSF dressings are beneficial in promoting the healing process, reducing healing times, enhancing patients' HRQoL, and in allowing a more cost-effective procedure.
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http://dx.doi.org/10.12968/jowc.2021.30.Sup4.S42DOI Listing
April 2021

The Feasibility and Effectiveness of Wearable Sensor Technology in the Management of Elderly Diabetics with Foot Ulcer Remission: A Proof-Of-Concept Pilot Study with Six Cases.

Gerontology 2021 3;67(4):493-502. Epub 2021 Mar 3.

Bioengineering College and Department of Endocrinology, Chongqing University Central Hospital, Key Laboratory for Biorheological Science and Technology of Ministry of Education, Chongqing University, Chongqing, China,

Aims: Using specials wearable sensors, we explored changes in gait and balance parameters, over time, in elderly patients at high risk of diabetic foot, wearing different types of footwear. This assessed the relationship between gait and balance changes in elderly diabetic patients and the development of foot ulcers, in a bid to uncover potential benefits of wearable devices in the prognosis and management of the aforementioned complication.

Methods: A wearable sensor-based monitoring system was used in middle-elderly patients with diabetes who recently recovered from neuropathic plantar foot ulcers. A total of 6 patients (age range: 55-80 years) were divided into 2 groups: the therapeutic footwear group (n = 3) and the regular footwear (n = 3) group. All subjects were assessed for gait and balance throughout the study period. Walking ability and gait pattern were assessed by allowing participants to walk normally for 1 min at habitual speed. The balance assessment program incorporated the "feet together" standing test and the instrumented modified Clinical Test of Sensory Integration and Balance. Biomechanical information was monitored at least 3 times.

Results: We found significant differences in stride length (p < 0.0001), stride velocity (p < 0.0001), and double support (p < 0.0001) between the offloading footwear group (OG) and the regular footwear group on a group × time interaction. The balance test embracing eyes-open condition revealed a significant difference in Hip Sway (p = 0.004), COM Range ML (p = 0.008), and COM Position (p = 0.004) between the 2 groups. Longitudinally, the offloading group exhibited slight improvement in the performance of gait parameters over time. The stride length (odds ratio 3.54, 95% CI 1.34-9.34, p = 0.018) and velocity (odds ratio 3.13, 95% CI 1.19-8.19, p = 0.033) of OG patients increased, converse to the double-support period (odds ratio 6.20, 95% CI 1.97-19.55, p = 0.002), which decreased.

Conclusions: Special wearable devices can accurately monitor gait and balance parameters in patients in real time. The finding reveals the feasibility and effectiveness of advanced wearable sensors in the prevention and management of diabetic foot ulcer and provides a solid background for future research. In addition, the development of foot ulcers in elderly diabetic patients may be associated with changes in gait parameters and the nature of footwear. Even so, larger follow-up studies are needed to validate our findings.
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http://dx.doi.org/10.1159/000513729DOI Listing
November 2021

The Role of Oxidative Stress and Antioxidants in Diabetic Wound Healing.

Oxid Med Cell Longev 2021 4;2021:8852759. Epub 2021 Feb 4.

Department of Endocrinology, Multidisciplinary Diabetic Foot Medical Center, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing 400014, China.

Foot ulcers are one of the most common and severe complication of diabetes mellitus with significant resultant morbidity and mortality. Multiple factors impair wound healing include skin injury, diabetic neuropathy, ischemia, infection, inadequate glycemic control, poor nutritional status, and severe morbidity. It is currently believed that oxidative stress plays a vital role in diabetic wound healing. An imbalance of free radicals and antioxidants in the body results in overproduction of reactive oxygen species which lead to cell, tissue damage, and delayed wound healing. Therefore, decreasing ROS levels through antioxidative systems may reduce oxidative stress-induced damage to improve healing. In this context, we provide an update on the role of oxidative stress and antioxidants in diabetic wound healing through following four perspectives. We then discuss several therapeutic strategies especially dietary bioactive compounds by targeting oxidative stress to improve wounds healing.
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http://dx.doi.org/10.1155/2021/8852759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884160PMC
September 2021

Elevated Circulating Fetuin-B Levels Are Associated with Insulin Resistance and Reduced by GLP-1RA in Newly Diagnosed PCOS Women.

Mediators Inflamm 2020 30;2020:2483435. Epub 2020 Sep 30.

Key Laboratory of Diagnostic Medicine (Ministry of Education) and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, 400016 Chongqing, China.

Background: Previous studies have suggested that Fetuin-B seems to be a secreted adipokine related to metabolic diseases. However, the results have been inconsistent. Here, our objective is to investigate the changes in circulating Fetuin-B levels in women with polycystic ovary syndrome (PCOS) and analyze the association of Fetuin-B and insulin resistance (IR).

Methods: The current study is comprised of a cross-sectional study and a series of interventional studies. Oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp (EHC) were engaged to assess glucose tolerance and insulin sensitivity. Serum Fetuin-B levels were determined by ELISA.

Results: Serum Fetuin-B and TNF- levels were markedly increased in women with PCOS compared to healthy women. Circulating Fetuin-B was positively associated with body mass index, waist-to-hip ratio, the percentage of body fat (FAT%), systolic blood pressure, triglyceride, low-density lipoprotein cholesterol, fasting blood glucose, 2 h blood glucose after glucose overload, fasting insulin, 2 h insulin after glucose overload, HOMA-insulin resistance index (HOMA-IR), the area under the curve for insulin (AUCi), AUCg, and TNF-, while negatively associated with value and follicular stimulating hormone (FSH). During the EHC, Fetuin-B levels were found to be significantly increased in PCOS women. After a glucose challenge, serum Fetuin-B levels in healthy women were significantly increased. Lipid infusion reduced serum Fetuin-B levels in 30 healthy subjects. After six months of glucagon-like peptide-1 receptor agonist (GLP-1RA) intervention, serum Fetuin-B concentrations in PCOS women markedly decreased following ameliorated IR.

Conclusion: Our results indicate that Fetuin-B may be a biomarker of IR in individuals with PCOS. This trial is registered with ChiCTR-IIR-16007901.
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http://dx.doi.org/10.1155/2020/2483435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545451PMC
August 2021

Erratum to: Pharmaceutic application of vitamin D on particle-induced fibrotic effects through induction of Nrf2 signals.

Toxicol Res (Camb) 2020 Jul 7;9(4):589. Epub 2020 Aug 7.

Department of Occupational and Environmental Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Disease, School of Public Health, Soochow University, Suzhou 215123, PR China.

[This corrects the article DOI: 10.1093/toxres/tfaa003.].
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http://dx.doi.org/10.1093/toxres/tfaa064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467263PMC
July 2020

Ultrasensitive aptasensor for isolation and detection of circulating tumor cells based on [email protected] nanorods and DNA walker.

Biosens Bioelectron 2020 Nov 28;168:112516. Epub 2020 Aug 28.

Key Laboratory of Medical Diagnostics of Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China. Electronic address:

Herein, based on dual signal amplification by [email protected] nanorods ([email protected]) and enzyme-free DNA walker, a novel electrochemical aptasensor was developed for simultaneous isolation and detection of circulating tumor cells (CTCs). A membrane protein MUC1-targeting aptamer was used to specifically recognize and capture MCF-7 cells. Uracil DNA glycosylase could hydrolyze deoxyuracils of the aptamer to isolate the captured cells. Novel [email protected] with large surface area and high peroxidase activity were synthesized to amplify the signal, and the enzyme-free DNA walker was applied to release more signal probes combined with [email protected] Furthermore, to reduce steric hindrance by cells, the signal probes rather than the target cells, were directly combined with the electrode. The aptasensor could detect CTCs in the range of 2 to 2 × 10 cells mL with a limit of detection 1 cell mL. The developed aptasensor, which can simultaneously isolate and detect CTCs, has great application potential in the early monitoring of tumor metastasis and in individualized treatment.
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http://dx.doi.org/10.1016/j.bios.2020.112516DOI Listing
November 2020

Pharmaceutic application of vitamin D on particle-induced fibrotic effects through induction of Nrf2 signals.

Toxicol Res (Camb) 2020 Feb 20;9(1):55-66. Epub 2020 Mar 20.

Department of Occupational and Environmental Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Disease, School of Public Health, Soochow University, Suzhou 215123, PR China.

Fine particulate matter, a major air pollutant across the world, causes a series of pulmonary diseases. Vitamin D is a typical vitamin with emerging roles in inflammation and fibrosis. Different situations and diseases need different doses and modes of vitamin D administration, which challenges the existing vitamin D supplementary rules. Thus, studies of vitamin D applications and their mechanisms in various diseases are important for its future therapeutic applications. In this study, the therapeutic application of vitamin D in chronic particle-exposure-associated lung fibrosis and tissue remodeling was investigated. studies showed that vitamin D significantly attenuated fibrosis effects by decreasing α-smooth muscle actin-regulated extracellular matrix deposition and restoring expressions of E-cadherin and N-cadherin. With the importance of activated macrophage in the regulation of local epithelium and fibroblast in the process of tissue fibrosis, two separate systems of co-culture of macrophages with lung epithelium or fibroblast were built. The results confirmed that vitamin D promoted the proliferation of lung epithelium and depressed the fibrosis effects of fibroblasts as well. In addition, our results indicated that the therapeutic effects of vitamin D were through Nrf2 signals. Our work provides convincing experimental evidence for vitamin D therapeutic application to promote tissue repair and improve particle-associated lung fibrosis.
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http://dx.doi.org/10.1093/toxres/tfaa003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388330PMC
February 2020

Limb Salvage and Prevention of Ulcer Recurrence in a Chronic Refractory Diabetic Foot Osteomyelitis.

Diabetes Metab Syndr Obes 2020 30;13:2289-2296. Epub 2020 Jun 30.

Department of Endocrinology and Nephrology, Diabetic Foot Center, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing, People's Republic of China.

Biomechanical changes caused by structural foot deformities predispose patients to plantar ulceration. Plantar ulcer recurrence often leads to osteomyelitis, which is more commonly observed in patients with diabetes. Once the infection of diabetic foot ulcer (DFU) spreads and is complicated by osteomyelitis, treatment becomes more complicated and difficult. Osteomyelitis treatment remains challenging because of low drug concentration within the tissue caused by poor circulation and inadequate localized nutrition. Moreover, tissues around plantar ulcers are fewer and are thin, making the formation of granulation tissues difficult due to elevated plantar pressure. Furthermore, the skin around the wound is excessively keratinized, and the epidermis is hard to regenerate. Meanwhile, skin grafting at that site is often not successful due to poor blood circulation. Therefore, it is technically challenging to manage diabetic pressure plantar ulcer with osteomyelitis and prevent its recurrence. Here, we present a case of chronic DFU complicated by osteomyelitis due to foot deformity. The ulcer was successfully healed using advanced wound repair technology comprising of surgical bone resection, vancomycin-loaded bone cement implant, negative-pressure wound therapy, and autologous platelet-rich gel. Subsequently, preventive foot care with custom-made offloading footwear was prescribed. The plantar ulcer did not recur and improvement in biomechanical parameters was observed after the intervention. This case represents an effective and comprehensive management strategy for limb salvage and prevention in patients with complicated foot conditions.
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http://dx.doi.org/10.2147/DMSO.S254586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335304PMC
June 2020

Intractable hiccups as a rare gastrointestinal manifestation in severe endocrine and metabolic crisis: case report and review of the literature.

Ther Adv Endocrinol Metab 2020 20;11:2042018820934307. Epub 2020 Jun 20.

Department of Endocrinology and Nephrology, Chongqing Emergency Medical Hospital, Chongqing University Central Hospital, No.1 Jiankang Road, Yuzhong District, Chongqing 400014, China.

Diabetic ketoacidosis (DKA) and thyroid storm (TS) are severe metabolic and endocrine disorders. Both usually manifest with multiple systemic clinical signs and symptoms, and digestive symptoms, such as nausea and vomiting, are most common in these patients. Moreover, the presence of a concurrent severe or rare complication may worsen the condition or even cause death due to misdiagnosis, delayed diagnosis, or inappropriate treatment. The identification of these symptoms is usually closely related to the severity and prognosis of the disease. Although clinical prognosis might be improved by prompt diagnosis and aggressive treatment, some rare and insidious metabolic complications are difficult to identify early. Moreover, life-threatening gastrointestinal symptoms are very rare in patients with DKA and TS. Here, we report an inpatient diagnosed with DKA and Graves' disease who developed life-threatening intractable hiccups resulting in TS and respiratory failure during the treatment of DKA. In addition, we review the literature to discuss the possible underlying mechanism of intractable hiccups in the development of TS.
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http://dx.doi.org/10.1177/2042018820934307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307285PMC
June 2020

Re-evaluation of retested nucleic acid-positive cases in recovered COVID-19 patients: Report from a designated transfer hospital in Chongqing, China.

J Infect Public Health 2020 Jul 7;13(7):932-934. Epub 2020 Jun 7.

Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, PR China; The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases, The First Affiliated Hospital of Chongqing Medical University, PR China. Electronic address:

Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, Hubei Province, China [1], a large number of confirmed cases met the discharge criteria (one of which is two consecutive negative nucleic acid tests with an interval of at least 24 h) [2]. Previous studies have paid more attention to the epidemic situation of COVID-19 and patient diagnosis and treatment. Close attention also should be paid to the discharged patients. Surprisingly, a previous follow-up reported that some patients' nucleic acid retest results were positive again after discharge [3]. Factors impacting these follow-up test results should be further investigated. Since the first confirmed case was diagnosed in our hospital (Chongqing Emergency Medical Center, the designated transfer hospital) on February 4th, we confirmed a total of 17 cases. All patients infected with the novel coronavirus were transferred to a designated hospital in Southwest China's Chongqing by ambulance with an inbuilt negative-pressure chamber [4]. In the follow-up examination of these patients, RT-PCR tests were conducted again 3 days after discharged from the designated hospital. Four patients showed recurrence of positive results after a few days of discharge. Thus, we examined these cases herein, aiming to provide information for policy formulation and modification of discharge plans.
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http://dx.doi.org/10.1016/j.jiph.2020.06.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275981PMC
July 2020

Comparison of Allogeneic Platelet-rich Plasma With Autologous Platelet-rich Plasma for the Treatment of Diabetic Lower Extremity Ulcers.

Cell Transplant 2020 Jan-Dec;29:963689720931428

Department of Endocrinology and Nephrology, Chongqing University Central Hospital, Chongqing Emergency Medical Center, China.

Registration Number Of Clinical Trials: ChiCTR1900021317.
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http://dx.doi.org/10.1177/0963689720931428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563928PMC
June 2021

Two consecutive myocardial tissue insults for inpatients with COVID-19.

Crit Care 2020 May 26;24(1):259. Epub 2020 May 26.

Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL, 32610-0254, USA.

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http://dx.doi.org/10.1186/s13054-020-02981-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250263PMC
May 2020

Elevated cardiac biomarkers are associated with increased mortality for inpatients with COVID-19: A retrospective case-control study.

J Clin Anesth 2020 10 20;65:109894. Epub 2020 May 20.

Department of Intensive Care Unit, The Fifth Hospital of Wuhan, Wuhan, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.jclinane.2020.109894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237926PMC
October 2020

Central Sfrp5 regulates hepatic glucose flux and VLDL-triglyceride secretion.

Metabolism 2020 02 23;103:154029. Epub 2019 Nov 23.

The Key Laboratory of Laboratory Medical Diagnostics in the Ministry of Education and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. Electronic address:

Objective: Secreted frizzled-related protein 5 (Sfrp5) has been shown to be associated with energy homeostasis and insulin resistance in mouse models of obesity and diabetes. However, its central role in glucose and lipid metabolism is unknown.

Methods: HFD-fed rats received ICV infusions of vehicle or Sfrp5 during a pancreatic euglycemic clamp procedure. To delineate the pathway(s) by which ICV Sfrp5 modulates HGP and VLDL-TG secretion, we inhibited the hypothalamic K channel using glibenclamide, the DVC NMDA receptor with MK801, and selectively transected the hepatic branch of the vagal nerve while centrally infusing Sfrp5.

Results: ICV Sfrp5 in HFD-fed rats significantly increased the glucose infusion required to maintain euglycemia due to HGP inhibition during the clamp procedure; moreover, hepatic PEPCK and G6Pase expression was decreased, and InsR and Akt phosphorylation was increased in the liver. ICV Sfrp5 also decreased circulating triglyceride levels via inhibiting hepatic VLDL-TG secretion. These changes were accompanied by the inhibition of enzymes related to lipogenesis in the liver. ICV Sfrp5 significantly increased insulin-stimulated phosphorylation of InsR and Akt in the hypothalamus of HFD-fed rats, and insulin-stimulated immunodetectable PIP3 levels were higher in Sfrp5 group than in control group both in vitro and vivo. The glucose- and lipid-lowering effects of ICV Sfrp5 were eliminated by NMDA receptor or DVC K channel inhibition or HVAG.

Conclusions: The present study demonstrates that central Sfrp5 signaling activates a previously unappreciated InsR-Akt-PI3k-K channel pathway in the hypothalamus and brain-hepatic vagus neurocircuitry to decrease HGP and VLDL-TG secretion.
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http://dx.doi.org/10.1016/j.metabol.2019.154029DOI Listing
February 2020

Identification and quantitation of clinically relevant microbes in patient samples: Comparison of three k-mer based classifiers for speed, accuracy, and sensitivity.

PLoS Comput Biol 2019 11 22;15(11):e1006863. Epub 2019 Nov 22.

Department of Biosystems Engineering, University of Arizona, Tucson, Arizona, United States of America.

Infections are a serious health concern worldwide, particularly in vulnerable populations such as the immunocompromised, elderly, and young. Advances in metagenomic sequencing availability, speed, and decreased cost offer the opportunity to supplement or even replace culture-based identification of pathogens with DNA sequence-based diagnostics. Adopting metagenomic analysis for clinical use requires that all aspects of the workflow are optimized and tested, including data analysis and computational time and resources. We tested the accuracy, sensitivity, and resource requirements of three top metagenomic taxonomic classifiers that use fast k-mer based algorithms: Centrifuge, CLARK, and KrakenUniq. Binary mixtures of bacteria showed all three reliably identified organisms down to 1% relative abundance, while only the relative abundance estimates of Centrifuge and CLARK were accurate. All three classifiers identified the organisms present in their default databases from a mock bacterial community of 20 organisms, but only Centrifuge had no false positives. In addition, Centrifuge required far less computational resources and time for analysis. Centrifuge analysis of metagenomes obtained from samples of VAP, infected DFUs, and FN showed Centrifuge identified pathogenic bacteria and one virus that were corroborated by culture or a clinical PCR assay. Importantly, in both diabetic foot ulcer patients, metagenomic sequencing identified pathogens 4-6 weeks before culture. Finally, we show that Centrifuge results were minimally affected by elimination of time-consuming read quality control and host screening steps.
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http://dx.doi.org/10.1371/journal.pcbi.1006863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6897419PMC
November 2019

Association between serum TSH levels and metabolic components in euthyroid subjects: a nationwide population-based study.

Diabetes Metab Syndr Obes 2019 22;12:1563-1569. Epub 2019 Aug 22.

Department of Endocrinology and Nephrology, Chongqing University Central Hospital, Chongqing Emergency Medical Center, Chongqing, People's Republic of China.

Background: Whether a relationship exists between various metabolic factors and thyroid-stimulating hormone (TSH) levels in euthyroid persons remains unknown. This study aims to explore the relationship between TSH levels and metabolic factors in euthyroid individuals.

Methods: A total of 2,663 subjects were enrolled from a nationwide population-based cross-sectional survey of iodine nutrition, thyroid disease and diabetes in China (2014-2017). Euthyroid individuals were divided into four groups according to quartiles of TSH levels: group A (n=305, 0.3-1.3 mIU/L), group B (n=829, 1.3-2.2 mIU/L), group C (n=673, 2.2-3.2 mIU/L) and group D (n=349, 3.2-4.2 mIU/L). Anthropometric parameters, biochemical indicators and TSH levels were determined.

Results: A total of 2,156 euthyroid subjects with serum TSH levels within the normal range accounted for 86.8% of the sample. The systolic blood pressure (SBP) in group D was significantly higher than that in the other three groups. Group C displayed significantly lower thyroid peroxidase antibody (TPOAb) levels than the other three groups. Group C also had lower anti-thyroglobulin antibody (TgAb) levels than groups A and D, whereas the TgAb levels in group B were only lower than those in group A. Spearman's or Pearson's linear regression analysis showed that SBP (r=0.054; =0.013) was positively correlated with TSH, but cholesterol (TC) (r=-0.043, =0.047) was negatively correlated with TSH. Multiple stepwise regression analysis revealed that SBP, the urinary iodine concentration (UIC), waist circumference (WC), body mass index (BMI), TC, triglycerides (TGs) and low-density lipoprotein cholesterol (LDL-C) were independent predictors of serum TSH levels.

Conclusion: This large population-based study demonstrates a significant interaction between metabolic factors and TSH levels. An adverse weight status, high blood pressure levels, blood lipid metabolism disorder and excessive iodine intake may be early manifestations of thyroid disease in euthyroid subjects.
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http://dx.doi.org/10.2147/DMSO.S202769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6709806PMC
August 2019

Short-term efficacy and safety of repaglinide versus glimepiride as augmentation of metformin in treating patients with type 2 diabetes mellitus.

Diabetes Metab Syndr Obes 2019 17;12:519-526. Epub 2019 Apr 17.

Department of Endocrinology and Nephrology, Chongqing University Central Hospital, Chongqing Emergency Medical Center, Chongqing 400014, People's Republic of China.

Consistent evidence is still lacking on which one, glimepiride plus metformin or repaglinide plus metformin, is better in treating type 2 diabetes mellitus (T2DM). Therefore, this study was conducted to compare the short-term efficacy and safety of these two methods in treating T2DM. The literature research dating up to August 2018 was conducted in the electronic databases. The randomized controlled trials (RCTs) comparing the short-term (treatment period ≤12 weeks) efficacy and safety of these two methods in treating patients with T2DM were included. No language limitation was used in this study. The decreased hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and 2h plasma glucose (2hPG) levels were used as the primary outcome to assess the efficacy, and the adverse events and hypoglycemia were used as the secondary outcome to assess the safety. In total, 11 RCTs composed of 844 T2DM patients were included. The results showed that there were no significant differences in decreasing HbA1c and FPG levels between the two methods, but the estimated standardized mean differences favored the repaglinide plus metformin. Meanwhile, the repaglinide plus metformin was significantly more effective in decreasing 2hPG levels than glimepiride plus metformin. In addition, fewer patients reported adverse events and experienced hypoglycemia in the repaglinide plus metformin group. These results indicated that the repaglinide plus metformin might have some advantages over glimepiride plus metformin in the short-term treatment of patients with T2DM, and should be further explored.
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http://dx.doi.org/10.2147/DMSO.S198154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6489581PMC
April 2019

Long-Term Outcomes of BMMSC Compared with BMMNC for Treatment of Critical Limb Ischemia and Foot Ulcer in Patients with Diabetes.

Cell Transplant 2019 05 27;28(5):645-652. Epub 2019 Mar 27.

1 Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, PR China.

We first compared long-term clinical outcomes in treating critical limb ischemia (CLI) and foot ulcer in patients with diabetes between autologous bone marrow mesenchymal stem cell (BMMSC) and bone-marrow-derived mononuclear cell (BMMNC) transplants. Forty-one patients were enrolled and followed up for 3 years. They received an 18-day standard treatment before stem cell transplantation. Patients with bilateral CLI and foot ulcer were injected intramuscularly or basally with BMMSC, BMMNC, or normal saline (NS). Cox model analysis showed significant differences in the hazard ratio (HR) for amputation with treatment by BMMSC (HR 0.21 [95% CI (0.05, 0.95)], = 0.043), infection of foot (HR 5.30 [95% CI (1.89, 14.92)], = 0.002), and age ≥64 (HR 3.01 [95% CI (1.11, 8.15)], = 0.030), but no significant differences by BMMNC at 9 months after transplantation. Regarding ulcer healing and recurrence rate, the BMMSC group demonstrated a significant difference from the NS group during the 3-6 months after transplantation or healing, but the BMMNC group did not. This trial suggests that, compared with BMMNC treatment, BMMSC treatment leads to a longer time of limb salvage and blood flow improvement, and, when compared with conventional therapy, it can promote limb blood flow and ulcerative healing, and reduce ulcer recurrence and amputation within 9 months.
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http://dx.doi.org/10.1177/0963689719835177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103602PMC
May 2019

Platelet-rich plasma plays an antibacterial, anti-inflammatory and cell proliferation-promoting role in an in vitro model for diabetic infected wounds.

Infect Drug Resist 2019 29;12:297-309. Epub 2019 Jan 29.

Department of Endocrinology, Southwest Hospital, Army Medical University, Chongqing, People's Republic of China,

Aim: This study was designed to examine the potential mechanism underlying these roles of platelet-rich plasma in treating diabetic foot ulcers (DFUs).

Methods: and HaCaT were co-cultured under high glucose conditions to serve as an in vitro model for infected cells in DFUs. Platelet-rich gel (PRG) or extract liquid of platelet-rich gel (EPG) were used to interfere with the model to observe the growth of HaCaT cells and , and the effect of miR-21 changes in HaCaT cells on PDCD4, NF-κB activity and related inflammatory factors.

Results: Incubation of HaCaT cells with promoted the decline of cell proliferation. Under this condition, the level of PDCD4 and the activity of NF-κB were increased in HaCaT cells with concomitant increased of IL-6, TNF-α and decreased IL-10, TGF-β1 in cultured supernatant. Both of PRG and EPG exhibited specific anti- activity where they protect HaCaT cells from bacterial damage and promote cell proliferation. Meanwhile, EPG was observed to increase intracellular miRNA-21 while reduce PDCD4 expression and inhibit NF-κB activity to suppress the inflammation in HaCaT cells.

Conclusion: This in vitro model provides a valuable tool for study of wound healing in the treatment of DFUs. Our results suggest that miRNA-21 may regulate the expression of NF-κB through PDCD4 where it plays an anti-inflammatory role and promote proliferation in infected DFUs treated by PRP. These findings could provide novel therapeutic targets for refractory wounds.
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http://dx.doi.org/10.2147/IDR.S186651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357877PMC
January 2019

C1q/TNF-related protein-6 is associated with insulin resistance and the development of diabetes in Chinese population.

Acta Diabetol 2018 Dec 7;55(12):1221-1229. Epub 2018 Aug 7.

Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.

Aims: C1q/tumor necrosis factor-related protein-6 (CTRP6) is a novel adipokine and has emerged as an important mediator for lipid and glucose metabolism. However, to date, the relationship between CTRP6 and T2DM in humans has not been demonstrated. Our objective is to investigate the association of circulating CTRP6 with T2DM in a cross-sectional study.

Methods: 118 patients with newly diagnosed T2DM, 98 subjects with impaired glucose tolerant (IGT) and 132 healthy subjects were recruited for this study. OGTT were performed in 48 healthy individuals to investigate the association of CTRP6 with glucose, insulin and other adipokines. Circulating CTRP6, TNF-α and Adipoq were measured by ELISA.

Results: IGT and T2DM individuals had higher serum CTRP6 levels than healthy controls (406.2 ± 136.6 and 539.1 ± 169.7 vs. 354.3 ± 117.2 ng/mL; both P < 0.01), whereas serum CTRP6 concentrations were further increased in T2DM patients compared with IGT individuals (P < 0.01). Serum CTRP6 levels were found to be related positively to BMI, WHR, FAT%, TC, TG, HbA1c, FBG, 2 h-OGTT, fasting insulin (FIns), 2 h-Ins, HOMA-IR and TNF-α, and negatively with HDL-C and Adipoq in all individuals (P < 0.05 or P < 0.01). Multivariate logistic regression analysis demonstrated that CTRP6 was correlated with both IGT and T2DM. After an oral glucose challenge, serum CTRP6 concentrations exhibited a similar change with blood glucose, insulin, TNF-α and Adipoq.

Conclusions: CTRP6 may be a metabolism- and nutrition-related adipokine and may be related to insulin resistance and T2DM.

Trial Registrations: Clinical Trial Registration Number: ChiCTR-OCC-11001422. Registration name: Plasma cytokines and endothelial function in type 2 diabetes.
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http://dx.doi.org/10.1007/s00592-018-1203-2DOI Listing
December 2018

Efficacy and long-term longitudinal follow-up of bone marrow mesenchymal cell transplantation therapy in a diabetic patient with recurrent lower limb bullosis diabeticorum.

Stem Cell Res Ther 2018 04 10;9(1):99. Epub 2018 Apr 10.

Department of Endocrinology and Nephrology, Diabetic Foot Center, Affliated Central Hospital of Chongqing University, Chongqing Emergency Medical Hospital, Chongqing, China.

Bullosis diabeticorum is a rare presentation of cutaneous manifestation most commonly affecting the lower limbs in patients with diabetes. The appearance, often as insidious as its resolution, is characterized by tense blisters on the skin surfaces of the lower limbs and the feet. The cause still remains unclear, but it may relate to microangiopathy and neuropathy. In this report, we present a case of a 64-year-old male with multiple episodes of blistering in the left lateral lower limb after a traumatic fall who was subsequently diagnosed with type 2 diabetes mellitus. The patient had a history of poorly controlled blood glucose and subsequently developed vasculopathy and peripheral neuropathy. Despite appropriate glycemic control and antibiotics therapy, the patient developed recurrent bullosis diabeticorum on five separate occasions during a 2-year span from 2005 to 2007. Building on our success with ischemic diabetic foot, we used bone marrow mesenchymal stem cell (BMMSC) transplantation therapy for bullosis diabeticorum. After a 9-month treatment, this patient developed another episode of cellulitis in the same lower limb which was successfully treated with antibacterial therapy. It is interesting that the patient reported no recurrence in the next 10-year follow-up span. This study demonstrates that bullosis diabeticorum could appear even before the onset of diabetes, and vascular insufficiency predisposes to the occurrence of bullosis diabeticorum. Our findings suggest that autologous BMMSC transplantation therapy may be an effective measure for recurrent bullosis diabeticorum; however, this will require further investigation to be conclusive. Early identification of diabetes and its complications and appropriate treatment may improve clinical outcomes and prevent lower limb amputation.

Trial Registration: ClinicalTrials.gov Identifier: NCT00955669 . Registered on August 10, 2009.
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http://dx.doi.org/10.1186/s13287-018-0854-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891952PMC
April 2018

Psychosocial intervention for patients with type 2 diabetes mellitus and comorbid depression: a meta-analysis of randomized controlled trials.

Neuropsychiatr Dis Treat 2017 24;13:2681-2690. Epub 2017 Oct 24.

Department of Endocrinology and Nephrology, Chongqing Emergency Medical Center, the Fourth People's Hospital of Chongqing, Chongqing, China.

Background: The efficacy of psychosocial intervention has been proven in treatment of diabetic patients with depression in some studies. This meta-analysis was conducted to explore the efficacy as well as additional effects of this method during diabetic management in patients with type 2 diabetes mellitus (T2DM) and comorbid depression.

Methods: Electronic databases were searched from March 2000 to March 2017 for randomized controlled trials (RCTs) studying the effects of psychosocial intervention on T2DM patients with depression. There was no language limitation. Outcome measurements were symptoms of depression and anxiety, as well as glycemic control. A random effects model was conducted.

Results: In total, 31 RCTs composed of 2,616 patients were eligible for this analysis. The psychosocial intervention was effective for depression symptoms with pooled standardized mean difference (SMD) of -1.50 (95% CI =-1.83, -1.18) and anxiety symptoms with SMD of -1.18 (95% CI =-1.50, -0.85). Meanwhile, the additional effects indicated a better improvement of glycemic control, including the fasting blood-glucose with SMD of -0.93 (95% CI =-1.15, -0.71), 2-hour postprandial plasma glucose with SMD of -0.84 (95% CI =-1.13, -0.56), and hemoglobin A1c with SMD of -0.81 (95% CI =-1.10, -0.53).

Conclusion: These results demonstrate that the psychosocial intervention is very effective in treating T2DM patients with depression.
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http://dx.doi.org/10.2147/NDT.S116465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5661466PMC
October 2017

Treatment of pretibial myxedema with intralesional immunomodulating therapy.

Ther Clin Risk Manag 2017 8;13:1189-1194. Epub 2017 Sep 8.

Department of Endocrinology and Nephrology, Chongqing Emergency Medical Hospital (The Fourth People's Hospital of Chongqing).

Objective: Local immune regulation therapy has been one of the therapeutic methods used for the treatment of autoimmune thyroid disease in patients with pretibial myxedema (PTM). However, the poor response rate and high recurrence rate are still major problems. Whether a premixed corticosteroid, compound betamethasone, could enhance remission rate and decrease recurrence rate in patients with PTM was investigated in the present study.

Subjects And Methods: We have performed a clinical utility observation of compound betamethasone with intralesional injections based on basic thyroid disease treatment in 32 PTM patients between January 2008 and August 2016. The patients were followed up for 2 years, and the clinical outcomes and side effects were calculated and analyzed.

Results: All patients had a complete remission after different times of injection. A total of 21.7% patients had complete remission with one time of injection, 34.8% with two times of injection, 17.4% with three times of injection, 4.3% with four times of injection, and 4.3% with five times of injection. In all, 56.3% patients with a disease duration of <6 months had complete remission after a 1-month treatment, 37.5% patients with a disease duration between 6 months and 12 months had complete remission after a 2-month treatment, 3.1% patients with a disease duration of 2 years had complete remission after a 5-month treatment, and 3.1% with a disease duration of 5 years had complete remission after a 7-month treatment.

Conclusion: Compound betamethasone with multipoint intralesional injection is a feasible, effective, and secure novel strategy in the treatment of PTM.
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http://dx.doi.org/10.2147/TCRM.S143711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5598751PMC
September 2017

ADP-ribosylation factor-like GTPase 15 enhances insulin-induced AKT phosphorylation in the IR/IRS1/AKT pathway by interacting with ASAP2 and regulating PDPK1 activity.

Biochem Biophys Res Commun 2017 05 18;486(4):865-871. Epub 2017 Mar 18.

Department of Clinical Laboratory, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Electronic address:

Decreased phosphorylation in the insulin signalling pathway is a hallmark of insulin resistance. The causes of this phenomenon are complicated and multifactorial. Recently, genomic analyses have identified ARL15 as a new candidate gene related to diabetes. However, the ARL15 protein function remains unclear. Here, we show that ARL15 is upregulated by insulin stimulation. This effect was impaired in insulin-resistant pathophysiology in TNF-α-treated C2C12 myotubes and in the skeletal muscles of leptin knockout mice. In addition, ARL15 localized to the cytoplasm in the resting state and accumulated in the Golgi apparatus around the nucleus upon insulin stimulation. ARL15 overexpression can enhance the phosphorylation of the key insulin signalling pathway molecules IR, IRS1 and AKT in C2C12 myotubes. Moreover, ARL15 knockdown can also specifically inhibit the phosphorylation of PDPK1 Ser241, thereby reducing PDPK1 activity and its downstream phosphorylation of AKT Thr308. Co-immunoprecipitation assays identified ASAP2 as an ARL15-interacting protein. In conclusion, we have identified that ARL15 acts as an insulin-sensitizing effector molecule to upregulate the phosphorylation of members of the canonical IR/IRS1/PDPK1/AKT insulin pathway by interacting with its GAP ASAP2 and activating PDPK1. This research may provide new insights into GTPase-mediated insulin signalling regulation and facilitate the development of new pharmacotherapeutic targets for insulin sensitization.
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http://dx.doi.org/10.1016/j.bbrc.2017.03.079DOI Listing
May 2017
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