The incidence of immune checkpoint inhibitor (ICI)-induced type 1 diabetes mellitus (ICI-T1DM) has increased as the use of ICIs has increased. Autoimmune ICI-T1DM often presents as diabetic ketoacidosis, resulting from insulin deficiency, among which insulin resistance is extremely rare. Here, we describe a patient with advanced myxoid liposarcoma who developed sintilimab-induced fulminant autoimmune diabetes associated with insulin resistance and metabolic disorders. The patient eventually required the combined use of insulin, metformin, liraglutide, and dapagliflozin to reduce blood glucose due to erratic glycaemic excursions and high insulin requirements during his duration of hospital stay. Metformin, dapagliflozin and liraglutide were discontinued because of weight loss half a year after discharge, and intensive insulin therapy was continued. The patient's blood glucose control was poor, and liraglutide and metformin were then added again, half a year later. Together, metformin, dapagliflozin and liraglutide in combination with insulin may help control blood glucose in ICI-induced DM patients with insulin resistance.

Podocytes are highly specialized glomerular epithelial cells that play a crucial role in maintaining the glomerular filtration barrier, impairment of which usually leads to proteinuria. The phenotypic alterations of podocytes are described to be one of the critical mechnisms underlying podocyte detachment from the glomerular basement membrane. High glucose is the major factor mediating the renal damages and podocyte injuries in the process of diabetic nephropathy. It was revealed that high glucose stimulated the epithelial-to-mesenchymal transition of podocyte, thus contributing to proteinuria. When the podocytes converse from epithelial phenotype to mesenchymal phenotype, their migratory capacity significantly increases. Previously, cell migration is conventionally detected by the wound healing assay and the transwell assay. In this study, we investigated and comfirmed the possibility of using single cell motility assay for the anaysis of podocyte motility under high glucose condtition.

PURPOSE:To investigate the diagnostic value of synthetic MRI combined MUSE DWI and 3D-pCASL in hippocampal sclerosis (HS).METHOD:A total of 30 HS patients participated in the study. At the same time, 51 healthy volunteers were collected as the control group. All patients and healthy volunteers underwent epilepsy MR scanning protocol (including oblique coronal MAGiC, MUSE DWI, and axial 3D-pCASL) at 3.0 T MR scanner.The independent samples T test and Mann-Whitney U test were used to compare the differences of the apparent dispersion coefficient(ADC), cerebral blood flow(CBF) and quantitative parameters, including T1 relaxation time (T1), T2 relaxation time (T2), and proton density (PD) values, in the hippocampus of the affected side of HS and the contralateral and control groups, respectively. The diagnostic performance was evaluated using binary logistic regression analysis and area under the receiver operating characteristic (ROC) curves (AUC).RESULTS:Significant statistical differences in T1, T2, CBF, and ADC values were observed between the affected hippocampus of HS patients and contralateral and control hippocampus (all P < 0.005). The T2 has higher discrimination abilities compared with other univariable parameters, with the AUC of 0.899. The combined T2, ADC and CBF model had the best diagnostic performance of HS in MTLE patients with AUC, sensitivity and specificity of 0.946, 86.67 %, 93.33 %, respectively.CONCLUSIONS:Relaxometry parameters derived from synthetic MRI contributed to diagnosis of HS. The proposed approach combining T2, ADC and CBF showed a strong diagnostic capability.

Background Glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs) are involved in neuronal excitability, neurogenesis, and neuroinflammation. However, the roles of GRs and MRs in epilepsy in focal cortical dysplasia II (FCDII) have not been reported. Research Design and Methods We evaluated GRs and MRs expression and distribution in FCDII patients and methylazoxymethanol-pilocarpine-induced epilepsy model rats (MP rats), and the effects of a GR agonist on neurons in human FCDII and investigated the electrophysiological properties of rats' neurons after lentivirus-mediated GR knockdown or overexpression and GR agonist or antagonist administration. Results GR expression (not MR) was decreased in specimens from FCDII patients and model rats. GR agonist dexamethasone reduced neuronal excitatory transmission and increased neuronal inhibitory transmission in FCDII. GR knockdown increased the excitability of cultured neurons, and GR overexpression rescued the hyperexcitability of MP-treated neurons. Moreover, dexamethasone decreased neuronal excitability and excitatory transmission in MP rats, while GR antagonist exerted the opposite effects. Dexamethasone reduced the seizure number and duration by approximately 85% and 60% in MP rats within one to two hours. Conclusions These results suggested that GRs play an important role in epilepsy in FCDII and GR activation may have protective and antiepileptic effects in FCDII.

Objective:Falls often occur in patients with diabetic neuropathy due to biomechanical alternation. The implication of diabetic peripheral neuropathy (DPN) on gait and balance remains poorly understood.Methods:A total of 11 dynamic gait, balance and electrophysiological parameters were evaluated in 176 participants. The biomechanical parameters were compared between groups.Results:Stride length and stride velocity were significantly lower in all subgroups of DPN compared with healthy subjects (p<0.05). Stance phase and double support phase were significantly higher, but swing phase were significantly lower across all subgroups of DPN than healthy subjects (p<0.05). Under eyes-open standing, the ML and AP range parameters of CoM sway, ankle sway and hip sway, CoM sway index, ankle swing index in both subclinical and confirmed DPN patients were all significantly higher compared to healthy subjects (p<0.05). Under eyes-closed standing, AP range parameters of CoM sway in subclinical DPN and confirmed DPN patients were significantly higher than healthy subjects (p<0.05). The hip sway areas in diabetics were significantly higher compared to healthy subjects (p<0.05).Conclusion:The abnormal biomechanical parameters existed in the early stages of patients with DPN. The static balance under eyes-open and eye-closed condition is maintained by ankle joint compensation strategy and hip joint protection strategy. An early evaluation and better risk management is essential for diabetic patients with a history of more than 5 years even without DPN clinical symptoms and signs.Clinical Trial Registration Number:No. ChiCTR1800019179, www.chictr.org.cn.

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.

Malignant tumors are a major cause of death, and their incidence is increasing worldwide. Although the survival rate for some cancers has improved, treatments for other malignant tumors are limited, and their mortality rate continues to increase. People with type 2 diabetes have a higher risk of malignant tumors and a higher mortality rate than those without diabetes. Metformin is a commonly used hypoglycemic drug. In recent years, a growing number of studies have indicated that metformin has antitumor effects and increases the sensitivity of malignant tumors to chemotherapy. However, the effect of metformin on different tumors is currently controversial, and the mechanism of metformin's antitumor action is not fully understood. Insights into the effect of metformin on malignant tumors and the possible mechanism may contribute to the development of antitumor drugs.

ObjectiveTo investigate the prevalence and risk factors of diabetic kidney disease (DKD) among the patients with type 2 diabetes mellitus (T2DM) in rural and urban communities in the Chongqing Main City. MethodsA total of 735 T2DM patients from rural and urban communities in the Chongqing Main City were selected by stratified cluster random sampling. They were compared in terms of demographic characteristics, physical test results, metabolic indicators, compliance rate of diabetes comprehensive control and DKD prevalence. Multivariate logistic regression model was used to analyze the risk factors of DKD. Results①The prevalence of DKD was 31.3% in the T2DM patients, and was higher in the rural communities than that in the urban communities (35.9% vs 28.1%, P<0.01). ② There were statistical differences in the demographic characteristics, physical test results, metabolic indicators, and compliance rates between the patients from the urban and rural communities (P<0.05). ③ Systolic blood pressure (SBP, OR=2.393), course of diabetes (OR=2.471) and level of triglyceride (TG, OR=1.988) were independent risk factors, while taking ACEI (angiotensin converting enzyme inhibitors) or ARBs (angiotensin-receptor blockers, OR=0.163) were protective factors for DKD in the patients of rural communities. And, age (OR=1.682), SBP (OR=2.201), course of diabetes (OR=1.644), HbA1c (OR=2.844), uric acid (OR=2.182) were independent risk factors for those in the urban communities. ConclusionThe prevalence of DKD is higher in the rural communities than that in the urban communities. Attention should be paid to hyperlipidemia in rural communities. Blood glucose control should be strengthened in urban communities, and physicians should correct hyperuricemia and pay attention to the DKD screening in elderly population.

Endocrinology Department, The First Affiliated Hospital of the Third Military Medical University (Army Medical University), Chongqing, People’s Republic of China; Endocrinology and Nephrology Department, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing, People’s Republic of China; Endocrinology Department, Dazu Hospital of Chongqing Medical University, The People’s Hospital of Dazu, Chongqing, People’s Republic of China

Autologous platelet-rich plasma (au-PRP) has been widely used for the management of refractory chronic wounds. However, patients with diabetic lower extremity ulcers (DLEUs) usually have complicated clinical conditions, and the utility of au-PRP is limited. In this study, the feasibility, effectiveness, and safety of allogeneic platelet-rich plasma (al-PRP) and au-PRP were investigated and compared in the treatment of DLEUs. A total of 75 in-patients with type 2 diabetes were assigned to the al-PRP group ( n = 20), au-PRP group ( n = 25), and conventional wound therapeutic (CWT) group ( n = 30) matched by the ankle brachial index and ulcer size from December 2015 to August 2018. Based on metabolic and nutritional regulation, infective control, and topical wound management, al-PRP, au-PRP, and CWT were administered to each group, respectively. Evaluation of treatment outcomes was determined by the parameters of wound healing and adverse reactions. The therapeutic times and average concentration of platelets were not significantly different between the au-PRP and al-PRP groups. The wound healing times of the al-PRP group (56.9 ± 29.22 d) and au-PRP group (55.6 ± 33.8 d) were significantly shorter than those of the CWT group (88.0 ± 43.4 d) ( P < 0.01), but there was no significant difference between the groups with PRP treatment. Although there was no significant difference in the daily healing area among all groups ( P > 0.05), the trend of the healing rate in the al-PRP group (16.77 ± 12.85 mm 2 ), au-PRP group (14.31 ± 18.28 mm 2 ), and CWT group (9.90 ± 8.51 mm 2 ) gradually decreased. No obvious adverse reactions (fever, edema, pain, skin itching, rash, or other sensory abnormalities) were observed in either the au-PRP or the al-PRP groups. Both al-PRP and au-PRP could effectively and safely promote wound healing in patients with DLEUs. Alternatively, al-PRP could be used for DLEUs as an off-the-shelf solution when au-PRP is limited. Registration number of clinical trials: ChiCTR1900021317

[This corrects the article DOI: 10.1155/2018/7653904.].

Objective Circulating miR-146a is aberrantly expressed in patients with type 2 diabetes (T2D), probably resulting from gene polymorphisms. However, the role of polymorphism rs2910164 in T2D pathogenesis remains controversial. Thus, we designed a meta-analysis to investigate the association between rs2910164 and T2D. Methods PubMed and Embase were searched for eligible papers in English published through September 2, 2019. Random or fixed effect models were used to determine risk estimates according to heterogeneities. Results Four studies, involving 2,069 patients and 1,950 controls, were included. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to pool the effect size. The pooled ORs and 95% CIs were 1.501 (0.887-2.541), 1.102 (0.931-1.304), 1.276 (0.900-1.811), 1.204 (0.878-1.652), 1.238 (0.880-1.740), and 1.350 (0.904-2.016) under the homozygote, heterozygote (CG vs. GG and CC vs. CG), dominant, allele, and recessive models, respectively. Heterogeneity was detected in most genetic models, with subgroup analyses performed by ethnicity, genotyping method, and disease duration. The co-dominant model was determined to be the most appropriate genetic model. Conclusions Our findings suggested that polymorphism rs2910164 is not correlated with T2D susceptibility. However, the results should be interpreted with caution because of confounding factors.

Inwardly rectifying potassium (Kir) channels make it easier for K+ to enter into a cell and subsequently regulate cellular biological functions. Kir5.1 (encoded by KCNJ16) alone can form a homotetramer and can form heterotetramers with Kir4.1 (encoded by KCNJ10) or Kir4.2 (encoded by KCNJ15). In most cases, homomeric Kir5.1 is non-functional, while heteromeric Kir5.1 on the cell membrane contributes to the inward flow of K+ ions, which can be regulated by intracellular pH and a variety of signaling mechanisms. In the form of a heterotetramer, Kir5.1 regulates Kir4.1/4.2 activity and is involved in the maintenance of nephron function. Actually, homomeric Kir5.1 may also play a very important role in diseases, including in the ventilatory response to hypoxia and hypercapnia, hearing impairment, cardiovascular disease and cancer. With an increase in the number of studies into the roles of Kir channels, researchers are paying more attention to the pathophysiological functions of Kir5.1. This minireview provides an overview regarding these Kir5.1 roles.

Objective: To explore the effect of DPN on the gait and balance ability using new a biomechanical monitoring technology. Methods: 176 subjects were divided into 4 groups: Group A (no DPN signs and symptoms, NCV negative, 48), group B (no DPN signs and symptoms, NCV positive, 45), group C (with DPN signs and symptoms, NCV positive, 51) and group D (normal control, 32). The gait, balance, timed up and go test were conducted using the LEGSys and BalanSens system. The difference of biomechanics parameters and their relationship with NCV were analyzed. Results: The stride, stride to height ratio, walking speed, step height and swing (left) of diabetic groups were significantly lower than group D (P < 0.05). The support (left) and double support (right) of diabetic groups were significantly higher than group D (P < 0.05). In eyes-open hard surface stand test, the center of gravity (COG) sway range of side to side and front to back, the ankle sway range of side to side, the COG sway area, the ankle sway area, the COG sway index and the ankle sway index in group B and C were significantly higher than group D (P < 0.05). The stride length and stride to height ratio of group C were lower than group A (P < 0.05). The walking speed, step height and steps per minute of group C were significantly lower than group A and B (P < 0.05). In the eyes open or closed stand balance test, COG sway range of front to back and the sway index of group C were significantly higher than group A (P < 0.05). In the eyes open state, the ankle sway range of front to back, ankle sway index and COG sway velocity of group C were significantly higher than group A (P < 0.05). In the eyes closed state, the hip sway area of group C were higher than group A (P < 0.05). In the mCTSIB test, the COG sway index of group C were significantly higher than group A (P < 0.05). Conclusion: The biomechanics performance in diabetic patients are impaired and further worse by DPN. These defects may achieve an early detection by the new biomechanical monitoring technology. Disclosure W. Deng: None. F. Deng: None. B. Chen: None. Y. Ma: None. X. Jiang: None. D. Armstrong: None. H. Zhou: None. Funding Cultivation Project of Chongqing Youth Medical High-End Reserve Talents (2017HBRC015)

Hepatopulmonary syndrome (HPS) is a serious vascular complication in the setting of liver disease. Factors produced by the liver are essential to regulate pulmonary angiogenesis in the pathogenesis of HPS; however, the pathogenic mechanisms of pulmonary angiogenesis are not fully understood. We investigated the role of HPS rat serum exosomes (HEs) and sham-operated rat serum exosomes (SEs) in the regulation of angiogenesis. We found that HEs significantly enhance PMVEC proliferation, migration, and tube formation. We further identified miR-194 was the most notably increased miRNA in HEs compared to SEs. Once released, hepatocyte-derived exosomal miR-194 was internalized by PMVECs, leading to the promotion of PMVEC proliferation, migration, and tube formation through direct targeting of THBS1, STAT1, and LIF. Importantly, the pathogenic role of exosomal miR-194 in initiating angiogenesis was reversed by P53 inhibition, exosome secretion inhibition or miR-194 inhibition. Additionally, high levels of miR-194 were found in serum exosomes and were positively correlated with P(A-a)O 2 in HPS patients and rats. Thus, our results highlight that the exosome/miR-194 axis plays a critical pathologic role in pulmonary angiogenesis, representing a new therapeutic target for HPS.

目的 探讨痛风石破溃患者使用超声清创联合负压吸引治疗创面的临床疗效及安全性.方法 选择2014年9月至2017年12月我科住院的痛风合并痛风石破溃的患者96例,随机分为2组(n=48):试验组[年龄(51.3±7.6)岁,病程(6.8±1.1)年,BMI(25.7±1.2),创面面积(1.62±0.23) cm2]采取超声清创联合负压吸引术治疗,对照组[年龄(52.4±6.9)岁,病程(6.5±1.3)年,BMI(26.1±1.4),创面面积(1.65 ±0.21)cm2]采取常规手工清创换药治疗.比较2组患者的创面愈合程度、治愈率、显效率,以及治疗前后患处视觉模拟疼痛评分(visual analogue scale,VAS),住院费用和不良反应发生情况.结果 治疗后试验组:痛风石破溃创面疗效优于对照组(P＜0.05);第5天的显效率和第10、15、20、25、30天的治愈率显著高于对照组,患处VAS评分显著低于对照组,差异均有统计学意义(P＜0.05);2组间住院费用差异无统计学意义(P＞0.05);试验组超声清创过程中出现2例(4.2％)患处剧烈疼痛,对照组3例(6.3％)出现延迟愈合,两组不良反应发生率差异无统计学意义(P＞0.05).结论 超声清创联合负压吸引能够缩短痛风石破溃创面愈合时间、提高创面愈合质量、不增加不良反应发生率及总住院费用.

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.

Background and Objective: To observe the feasibility, efficacy and safety of al-PRP in the treatment of diabetic lower extremity ulcers. Furthermore, to explore the difference between au-PRP treatment, al-PRP treatment and only conventional treatment groups. Methods: A total of 75 inpatients with diabetic lower limbs ulcer (DLLU) were divided into au-PRP group (n=20), al-PRP group (n=25), conventional treatment group (n=30). All three groups were administered basic diabetic treatments. In addition, the above three different treatment methods were given. The feasibility, curative effect and safety of au-PRP in the treatment of DLLU were evaluated by observing wound healing time, the average daily healing area and adverse reactions. Results: No significant differences were observed in duration of diabetes, age, glycosylated hemoglobin, ankle brachial index, transcutaneous oxygen partial pressure, high-sensitivity C-reactive protein, IL-6, etc. among three groups (P>0.05). There was no significant difference in ulcer area and ulcer number between the three groups (8.43±6.93 cm2 vs. 5.64±3.91 cm2 vs. 9.73±9.72 cm2, P=0.19); The times and average of PRP treatment between two PRP groups have no significant difference (P>0.05). In the healing time, the al-PRP group and the au-PRP group were significantly shorter than the control group (56.9±29.22 days vs. 55.6±33.8 days vs. 88.0±43.4 days, P<0.01), while there was no significant difference between the al-PRP group and the au-PRP group (P>0.05). There was no significant difference in the average daily healing area (mm2) between the three groups (P>0.05). No significant adverse reactions (infection, itchy skin, redness, rash, etc.) were observed in two PRP groups. Conclusions: Al-PRP can effectively and safely promote the healing of diabetic lower extremity wounds. Al-PRP could be used as a beneficial cell therapy supplement when au-PRP is limited. Disclosure W. Deng: None. M. He: None. B. Chen: None. Y. Ma: None. D. Armstrong: None. J. Boey: None. Funding Natural Science Foundation of Chongqing (81500596)

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)], P = 0.043), infection of foot (HR 5.30 [95% CI (1.89, 14.92)], P = 0.002), and age ≥64 (HR 3.01 [95% CI (1.11, 8.15)], P = 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.