Differential roles of RIG-I like receptors in SARS-CoV-2 infection.

Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) sense viral RNA and activate antiviral immune responses. Herein we investigate their functions in human epithelial cells, the primary and initial target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A deficiency in MDA5, RIG-I or mitochondrial antiviral signaling protein (MAVS) enhanced viral replication. The expression of the type I/III interferon (IFN) during infection was impaired in MDA5-/- and MAVS-/-, but not in RIG-I-/-, when compared to wild type (WT) cells. The mRNA level of full-length angiotensin-converting enzyme 2 (ACE2), the cellular entry receptor for SARS-CoV-2, was ~ 2.5-fold higher in RIG-I-/- than WT cells. These data demonstrate MDA5 as the predominant SARS-CoV-2 sensor, IFN-independent induction of ACE2 and anti-SARS-CoV-2 role of RIG-I in epithelial cells.

Tuning the Crystallinity and Coverage of SiO2-ZnIn2S4 Core-Shell Nanoparticles for Efficient Hydrogen Generation.

The coverage, thickness, and crystallinity of ZnIn2S4 (ZIS) shells on SiO2 core nanoparticles (SiO2@ZIS) were systematically investigated using microwave-assisted solvothermal methods aided by the addition of acid in ethanolic medium. The surface modification of the SiO2 cores with (3-mercaptopropyl)trimethoxysilane was found to be critical to generate a homogeneous coverage of ZnIn2S4. The SiO2@ZIS core-shell nanoparticles exhibited the best coverage but poor crystallinity when synthesized in pure ethanol, whereas best crystallinity but poor coverage was observed when synthesized in an aqueous solution. The addition of selected amounts of acid (HCl) led to improved crystallinity in the ethanolic medium. The thickness of the ZIS shell could be controlled in an ethanolic solution by judiciously varying the amounts of acid and the concentration of the ZIS precursor. Increasing the concentration of the ZIS precursor to twice the standard concentration in ethanolic solution with the addition of 100 µL of HCl afforded better crystallinity, homogeneous coverage, and optimal photocatalytic hydrogen production.

Liraglutide prevents ß-cell apoptosis via inactivation of NOX2 and its related signaling pathway.

AIMS: High glucose (HG)-induced pancreatic ß-cell apoptosis may be a major contributor to the progression of diabetes mellitus (DM). NADPH oxidase (NOX2) has been considered a crucial regulator in ß-cell apoptosis. This study was designed to evaluate the impact of GLP-1 receptor agonist (GLP-1Ra) liraglutide on pancreatic ß-cell apoptosis in diabetes and the underlying mechanisms involved. METHODS: The diabetic rat models induced by streptozotocin (STZ) and a high fat diet (HFD) received 12 weeks of liraglutide treatment. Hyperglycemic clamp test was carried out to evaluate ß-cell function in vivo. Flow cytometry analysis was used to measure apoptosis rates in vitro. DCFH-DA method was used to detected ROS level in vivo and in vitro. RESULTS: Liraglutide significantly improved islet function and morphology in diabetic rats and decreased cell apoptosis rates. Thr183/Thr185 p-JNK1/2 and NOX2 levels reduced in diabetic rats and HG-induced INS-1 cell following liraglutide treatment. In addition, liraglutide upregulated the phosphorylation of AMPKα (p-AMPKα), which prevented NOX2 activation and alleviated HG-induced ß-cell apoptosis. CONCLUSION: The p-AMPKα/NOX2/JNK1/2 pathway is essential for liraglutide to attenuate HG-induced ß-cell apoptosis, which further proves that GLP-1Ras may become promising therapeutics for diabetes mellitus.

Prevalence of dyslipidemia and its control in type 2 diabetes: A multicenter study in endocrinology clinics of China.

OBJECTIVE: The aim of this study was to assess the levels of serum lipid and awareness, treatment, and control of dyslipidemia in type 2 diabetes mellitus (T2DM) patients from top-ranked endocrinology clinics in large cities of China. MATERIALS AND METHODS: A cross-sectional study in a representative sample of 4807 Chinese adults 40 to 75 years of age was conducted during 2010 to 2011 at 20 endocrinology clinics in top-ranked hospitals covering most of the major cities of China. Serum lipid levels were measured, and treatment of dyslipidemia was recorded and assessed. RESULTS: In the present study, the prevalence of dyslipidemia was 67.1% in T2DM subjects. Among those with dyslipidemia, the proportion of awareness and treatment was 68.7% and 55.9%. Among participants with lipid-lowering therapy, 686 subjects achieved the low-density lipoprotein cholesterol (LDL-C) control less than 2.60 mmol/L, with the rate being 39.4%. In those patients with previous cardiovascular disease, the percentage of participants who achieved LDL-C goal (1.80 mmol/L) was 15.3%. CONCLUSION: The prevalence of dyslipidemia is high, and the awareness, treatment, and control of dyslipidemia are relatively low in Chinese T2DM patients. This calls for the awareness and intervention of dyslipidemia in these patients.

Clinical outcomes of toe amputation in patients with type 2 diabetes in Tianjin, China.

The aim of this study is to determine the predictors for reulceration, reamputation and mortality in patients with diabetes following toe amputation, and the impact of activities of daily living on clinical outcomes. This prospective cohort study included 245 patients who had undergone toe amputation (202 healing and 43 non-healing) and was followed for a 5-year period. Data regarding new foot ulceration, reamputation and mortality were recorded, and the patients' activities of daily living were evaluated. The rate of wound healing was 82·4%. The rate of follow-up in the healed group was 91·6%. In years 1, 3 and 5, the cumulative incidence of patients who developed a new foot ulcer was 27·3%, 57·2% and 76·4%, respectively, leading to reamputation in 12·5%, 22·3% and 47·1%, respectively. The cumulative mortality was 5·8%, 15·1% and 32·7% at 1, 3 and 5 years, respectively. Multivariate analysis showed that GHbA1c > 9% (75 mmol/mol) was identified as an independent predictor of impaired wound healing, reulceration and reamputation. An age of >70 years was identified as an independent predictor of reamputation, mortality and impairment of activities of daily living. Despite a satisfactory initial healing rate after the first toe amputation, with the extension course after the toe amputation, the long-term outcomes are not optimistic. In developing countries like China, taking measures to prevent reulceration and reamputation is very important for patients with diabetic foot minor amputations, especially following toe amputation.

Chemerin expression in Chinese pregnant women with and without gestational diabetes mellitus.

OBJECTIVES: The aim of this study was to determine the effect of obesity, gestational diabetes mellitus (GDM) on circulating chemerin concentrations and chemerin gene expression of adipotissue in pregnancy women. MATERIAL AND METHODS: Totally 42 normal glucose tolerant (NGT) women and 48 women with GDM were included in this study. Their clinical features and biochemical parameters were analyzed. The NGT and GDM women were subgrouped by prepregnancy BMI as normal-weight group, overweight group, and obese group, respectively. Serum chemerin and tumor necrosis factor α (TNF-α) of these individuals were determined by ELISA methods, and subcutaneous adipose tissues' mRNA expressions of chemerin and CMKLR1 (encoding the receptor of chemerin) were analyzed by real-time PCR. RESULTS: Serum chemerin in obese-NGT group and normal-weight-GDM group was significantly higher than that of normal-weight-NGT group. Chemerin and CMKLR1 mRNA expression of subcutaneous adipose tissue was lower in the obese-NGT group than normal-weight-NGT group. There was no significant difference of CMKLR1 mRNA expression between normal-weight-NGT and normal-weight-GDM group. Serum chemerin significantly and positively correlated with triglycerides (TG) and homeostasis model assessment of insulin resistance (HOMA-IR) assessed both by uni- and multivariate. CONCLUSIONS: Gestational obesity, GDM may contribute to the elevating serum chemerin. Serum chemerin in pregnancy was associated with insulin resistance and triglycerides. Chemerin gene may play a role both in obese and GDM patients. CMKLR1 might exert its action only in obese individuals, not in GDM patients before delivery.

Risk factors and gene type for infections of MRSA in diabetic foot patients in Tianjin, China.

The objective was to study risk factors and gene type of DF patients infected with MRSA. A total of 429 DF patients were recruited. The patients with S aureus infections were divided into MRSA and MSSA groups. MRSA were genotyped by SCCmec. pvl and lukE-lukD were detected. A total of 559 pathogens were isolated from them, with G+ bacteria firstly(59.0%), followed G- bacilli (37.7%) and true fungi (3.3%). The 3 most frequently isolated pathogens were S aureus (35.2%), S epidermidis (12.3%), and Pseudomonas aeruginosa (11.2%). SCCmec III MRSA and SCCmec IVa MRSA had the same antibacterial spectrum. mecA positive rate was 100%. lukE-lukD and pvl positive rates were 100% and 0%, respectively. 28 strains belonged to SCCmec III and the others belonged to SCCmec IVa. The G+ cocci were the main pathogens, S aureus and S epidermidis were predominant among them. Antibiotic usage in 6 months prior to hospitalization, long course of ulcer, osteomyelitis and hypoproteinemia are risk factors for MRSA. SCCmec IVa is high in proportion to MRSA isolates, suggesting that CA-MRSA has become major pathogen of DF infection. All the MRSA were harboring lukE-lukD, which has been reported to present poor leucotoxin compared to pvl, and may be a response to atypical local inflammatory reaction in DF infection.

[The safety and effectiveness of once daily detemir in patients with type 2 diabetes previously failing oral agents: the Chinese cohort from SOLVE(TM) observational study].

OBJECTIVE: Study of Once-daily LeVEmir(®) (SOLVE(TM)) was a 24-week international observational study to evaluate the safety and effectiveness of initiating once-daily insulin detemir (Levemir) as add-on therapy in patients with type 2 diabetes mellitus (T2DM) who failed treatment of oral anti-diabetic drugs (OAD). METHODS: The present study was derived from the data of Chinese cohort. A total of 3272 patients with T2DM failing OAD were enrolled in the study. Determir were prescribed to the patients by the decision of the physician. Clinical data were collected at baseline, week 12 and week 24 to evaluate the safety and effectiveness of detemir. RESULTS: The age of the patients was (56.2 ± 10.8) years with a diabetes duration of (7.1 ± 5.2) years. Their BMI was (25.3 ± 3.3) kg/m(2). No patient experienced any major or nocturnal hypoglycaemic event during the study. After 24 weeks of treatment, the glycosylated hemoglobin A1c (HbA1c) decreased from (8.33 ± 1.69)% to (7.16 ± 1.18)% with a mean change of -1.17%, the fasting plasma glucose decreased from (9.52 ± 2.59) mmol/L to (6.84 ± 1.42) mmol/L with a mean change of -2.7 mmol/L, and the 7-point blood glucose profile improved overall. Totally 49.1% of patients achieved HbA1c < 7%. The mean body weight decreased by 0.15 kg. CONCLUSIONS: Insulin detemir administered once daily as add-on therapy in patients with T2DM failing OAD regimen significantly reduces the risk of major hypoglycemia, improves glycemic control, increases the percentage of patients achieving treatment target with neutral effect on body weight.

[Risk factors for infections of methicillin-resistant Staphylococci in diabetic foot patients].

OBJECTIVE: To examine the distribution patterns of pathogens isolated from the patients with diabetic foot ulcers and explore the risk factors for infections of methicillin-resistant S. aureus (MRSA) or methicillin-resistant S. epidermidis (MRSE). METHODS: A total of 388 diabetic-foot patients hospitalized at Tianjin Metabolic Diseases Hospital between January 2008 and June 2010 were recruited. The distribution profiles of pathogens isolated from diabetic foot ulcers were summarized. The patients with S. aureus infections were divided into MRSA and MSSA groups while those with S. epidermidis infections into MRSE and MSSE groups. The clinical features of these patients were compared between all groups. Logistic regression was employed to identify the risk factors for the MRSA/MRSE infections. RESULTS: A total of 362 pathogens were isolated from them. And the Gram-positive bacteria were the most predominant (57.2%, 207/362), followed by Gram-negative bacilli (39.2%, 142/362) and true fungi (3.6%, 13/362). The three most frequently isolated pathogens were S. aureus (27.1%), S. epidermidis (18.8%) and Pseudomonas aeruginosa (15.5%). Statistically significant differences existed in antibiotic usage in 6 months prior to hospitalization, course of ulcer, ulcer size, deep ulcer, osteomyelitis, hypertension, anemia, hypoproteinemia and erythrocyte sedimentation rate between the patients infected with MRSA and MSSA (P < 0.05). The MRSE infection was correlated with recurrent ulcer, osteomyelitis, hypoproteinemia, HbA1c and lower total serum protein (P < 0.05). Multiple Logistic regression analysis revealed that antibiotic usage in 6 months prior to hospitalization, long course of ulcer, osteomyelitis, hypertension and hypoproteinemia were risk factors for the MRSA infection. And HbA1c was a risk factor for the MRSE infection. CONCLUSION: In the present study, the Gram-positive cocci are the main pathogens isolated from diabetic foot ulcers. And S. aureus and S. epidermidis are the most frequently isolated pathogens. Antibiotic usage in 6 months prior to hospitalization, long course of ulcer, osteomyelitis, hypertension and hypoproteinemia are risk factors for the MRSA infection. And HbA1c is a risk factor for the MRSE infection.

[The baseline characteristics of patients with type 2 diabetes initiating insulin detemir : the Chinese cohort from the SOLVE(TM) study].

OBJECTIVE: To characterize the baseline status of Chinese diabetic patients based on data derived from Chinese cohort from SOLVE(TM) study. METHODS: Patients with type 2 diabetes initiating basal insulin detemir at the decision of the physician were eligible for the study. Data on demographics, medical history, glycemic profile and treatment regimen at baseline were collected by physicians. RESULTS: A total of 3272 patients [female 42%, male 58%, mean age (56.2 ± 10.8) years] were included in the study. Their BMI was (25.3 ± 3.3) kg/m(2). The duration of diabetes was 4.0 (0.1 - 27.0) years, and the duration of treatment with oral antidiabetic drugs (OADs) was 3.0 (0.0 - 20.2) years. The proportions of subjects with diabetic macro- and micro-vascular complications were 15.8% (515 cases) and 27.1% (866 cases), respectively. The hemoglobin A1c (HbA1c) at baseline was (8.33 ± 1.70)%, and the fasting blood glucose (FPG) was (9.5 ± 2.6) mmol/L. CONCLUSIONS: A large proportion of patients with type 2 diabetes remain in poor glycemic control, and the prevalence of diabetic complications is high, which requires optimal therapeutic strategy for the patients with suboptimal glycemic control.

Consistent sparse representations of EEG ERP and ICA components based on wavelet and chirplet dictionaries.

A randomized search algorithm for sparse representations of EEG event-related potentials (ERPs) and their statistically independent components is presented. This algorithm combines greedy matching pursuit (MP) technique with covariance matrix adaptation evolution strategy (CMA-ES) to select small number of signal atoms from over-complete wavelet and chirplet dictionaries that offer best approximations of quasi-sparse ERP signals. During the search process, adaptive pruning of signal parameters was used to eliminate redundant or degenerative atoms. As a result, the CMA-ES/MP algorithm is capable of producing accurate efficient and consistent sparse representations of ERP signals and their ICA components. This paper explains the working principles of the algorithm and presents the preliminary results of its use.

[Impact of advanced glycosylation end products-modified human serum albumin on migration of epidermal keratinocytes: an in vitro experiment].

OBJECTIVE: To explore the impact of advanced glycosylation end products (AGE)-modified human serum albumin (AGE-HSA) on keratinocyte migration and the mechanism thereof. METHODS: AGE-HSA was prepared in vitro. Epidermal keratinocytes from Sprague-Dawley rats' back were cultured and treated with AGE-HSA of the terminal concentrations of 0, 30, 60, 90, 120, and 150 microg/ml for 1, 3, 5, and 7 days respectively. MTT method was used to detect the keratinocyte adhesion rate, expressed by absorbance. Keratinocyte migration ability was assessed by scratch wound healing assay and Transwell assay. Expression of integrin alpha3 was determined by flow cytometry. Scanning electron and inverted microscopes were used to observe the pseudopodium and microfilament of the keratinocytes. Immunofluorescence staining was used to detect the form of F-actin in the cells. RESULTS: The adhesion rates of the keratinocyte cultured with AGE-HSA for 12 and 24 hours were (0.112 +/- 0.022) and (0.173 +/- 0.012) respectively, both significantly lower than those of the control group [(0.122 +/- 0.004) and (0.267 +/- 0.024) respectively, both P < 0.05)]. Scratch wound healing assay showed that the amount of migrating cells in the AGE-HSA group was (7 +/- 4)/HP, significantly less than that of the control group [(61 +/- 11)/HP, P < 0.05)], and Transwell assay showed that the amount of migrating cells in the AGE-HSA group was (72 +/- 18)/HP, significantly less than that of the control group [(288 +/- 52)/HP, P < 0.05]. The expression rate of keratinocyte integrin alpha3 in the AGE-HSA group was (3.2 +/- 1.2)%, significantly lower than that in the control group [(36.6 +/- 11.2)%, P < 0.05]. The spreading of cell body, and the formation of pseudopodium and microfilament of the AGE-HSA group were all depressed in comparison with the control group. CONCLUSION: Keratinocyte migration is inhibited by AGE accumulation in high glucose condition. The mechanism may be the abnormality in the integrin inside-out signaling pathway and AGE-RAGE signaling pathway.

[Differences in risk factors of diabetic foot in the patients in South and North China].

OBJECTIVE: To investigate the differences on the diabetic foot problems and its risk factors in south and north of China. METHODS: Patients with foot problems were surveyed from January 1 to December 31, 2004 in 14 teaching hospitals located in different cities in China, including demographic data, present and past history of the foot problems and peripheral artery disease (PAD), the classification of the foot ulcers based on the Wagner' system, control of the hyperglycemia and lipids disorder, medical cost in hospital and the diabetic complications. All the patients were divided into two groups due to their geographical data, south and north. RESULTS: There were 285 and 349 patients for the group south and group north. No significant differences were found for duration of diabetes or foot problems, fasting or post-meal glucose, total cholesterol, triglycerides, HDL-C, and the numbers of patients with smoke, hypertension, nephropathy or neuropathy between the two groups. There were significant differences for the age (70 yrs vs 66 yrs), percentage of the patients with average person income with over RMB 1000 per month (57.7% vs 45.6%), coronary heart disease (42.6% vs 61.0%) and retinopathy (35.7% vs 49.5%), HbA1c (7.90% vs 8.80 %), LDL-C (2.75 mmol/L vs 2.98 mmol/L), WBC (6.70 x 10(9) vs 7.40 x 10(9)/L), HCT (0.37 vs 0.38), creatinine (87 micromol/L vs 76 micromol/L) and uric acid (333 mmol/L vs 271 mmol/L), and amputation rate (2.6% vs 9.7%) between south and north groups. Logistic analysis showed that severity of the foot problems was associated with ABI and WBC in south group, and with ABI, PLT and HCT in north group. CONCLUSION: Diabetic foot problems were more severe, with more risk factors and with more medical cost in north patients.

[Research on the clinical features and effective factors of 249 diabetic patients with deep foot infection].

OBJECTIVE: 249 diabetic patients with deep foot infection were retrospectively studied. Their clinical features and effective factors related to wound healing were analyzed. METHODS: 249 patients team (physician, surgeon and diabetes-specific nurse) were divided into 3 groups. Group A: patients healed without amputation (n = 107), group B: patients healed after amputation (n = 114), and group C: patients didn't heal after amputation. All patients' clinical features, lab examinations and foot wound features were compared. RESULTS: The group A patient were (59 +/- 12) years old, significantly younger than the group B (67 +/- 11, P < 0.01). Hypersensitive C reactive protein (hs-CRP, 18 +/- 5 mg/L) and plasma albumin (32 +/- 7 g/L) of group A were significantly higher than those of group B (13 +/- 5 mg/L and 29 +/- 5 g/L, respectively, P < 0.01). The duration of diabetes mellitus of group B (17 +/- 11) year was significantly longer than that of group A (10 +/- 6 year, P < 0.05). The possibility of probing bone, purulent secretion, necrosis, bone exposure, cacosmia, edema and critical limb ischemia of group B were more frequent (P < 0.01 or P < 0.05) compared to group A. The age of group B (67 +/- 11) are younger than that of group C (72 +/- 9, P < 0.05). In group B, temperature (38.1 +/- 1.1) degrees C, white blood cell (WBC) count (10 +/- 3) x 10(9)/L and hs-CRP (13 +/- 5) mg/L were higher than those of group C (37.4 +/- 0.8 degrees C, 8 +/- 2 x 10(9)/L and 7 +/- 6 mg/L, respectively, all P < 0.05). Critical limb ischemia of group B (37%) was more frequent than that of group A (7%, P < 0.05), but less frequent than that of group C (77%, P < 0.01). hs-CRP and plasma albumin were protective factors for wound healing. Age, the possibility of probing bone, purulent secretion, necrosis, bone exposure, cacosmia, edema and critical limb ischemia were risk factors for wound healing. CONCLUSION: diabetic patients with deep foot infection are difficult to be diagnosed in early stage since they often have no significant clinical syndrome such as fever, redness, swelling and pain, and their WBC count does not increase. Though multidisciplinary team manages these patients, more than half of them need amputation. Wound healing in the patients is related to multiple factors, including age, duration of diabetes mellitus, hs-CRP, plasma albumin, WBC count, level of limb ischemia and wound features.

[A multicenter survey on the diabetic foot and its neuropathy in China].

OBJECTIVE: To investigate the characteristics of diabetic foot with neuropathy and its related factors. METHODS: 530 out- and in-patients in 14 grade A class 3 comprehensive hospitals in China with foot problems were surveyed. 337 of the 500 patients (63.58%) suffered from neuropathy, 172 (32.45%) with diabetic foot with simple neuropathy and 165 (31.13%) with simple neuropathy combined with peripheral artery disease (PAD). 193 of the 500 patients (36.42%) suffered from peripheral artery disease (PAD). 77.7% of ulcer were caused by physical factors. Questionnaire survey was conducted to collect the demographic data, present and past history, history of the hyperglycemia and lipid disorders, classification and phases of the foot ulcers based on Wagner' system and Texas system, characteristics of neuropathy and other diabetic complications, and relative risk factors. Detailed physical examination was performed, including 10 g nylon filament sensation examination. RESULTS: The duration of diabetic foot of the patients with simple neuropathy was 3 (1, 60) months, significantly shorter than that of the diabetic foot patients with PAD [5 (1, 96) months, P < 0.001]. The Wagner degree of ulcer was related to the duration of diabetes, economic income, foot deformity, nerve reflection, diapason vibration sensation of foot, sensation point of 10 g nylon filament, ankle/brachial index (ABI), foot artery pulse, fasting blood sugar (FBS) and glycated hemoglobin (HbA1c). Stepwise regression analysis revealed that ABI of left posterior tibial artery, vibration detection threshold and economic income were the most significant influencing factors of the degree of ulcer. CONCLUSION: Neuropathy ulcer is common in diabetic foot patients. The prognosis of healing in diabetic foot with neuropathy is prior to that of diabetic foot with PAD. The neuropathy and PAD of foot influence each other and aggravate the condition of diabetic foot. The examinations of diapason vibration sensation of foot, sensation point of 10 g nylon filament, and Achilles tendon reflex are simple and practical, and are worth recommending.

[The medical cost of diabetic patients with foot problems due to peripheral artery disease].

OBJECTIVE: To investigate the medical cost of diabetic patients with foot problems and peripheral artery disease. METHODS: Type 2 diabetic patients with foot problems admitted into the endocrinology departments of 14 teaching hospitals from Jan. 1 to Dec. 31, 2004 were surveyed for their type and phase of foot ulcers, diabetic complications, medical cost and general personal characteristics. RESULTS: The average medical cost of the hospitalization of these patients was RMB yen 14,906 +/- 7072 (about US $ 1640 +/- 873); medication and examination cost was separately 56% and 19% of the total cost. There was obviously higher medical cost for these patients with longer diabetes duration of over 20 years and with the occupation of laborer and retired worker. Patients with kidney disease had significantly higher medical cost than those without (RMB yen 11 690.7 vs yen 9493.0; P = 0.0013), even if the hospital stay was nearly the same (21 days vs 20 days). The medical cost increase with the severity of diabetic foot problems based on the classification of Wagner System or Texas System. Patients with infection, ischemic foot and gangrene foot stayed in the hospitals longer and had much higher medical cost. CONCLUSION: The medical cost is higher for diabetic patients with foot problems and is related with the presence of complicating kidney disease, infection and ischemia as well as the severity of foot ulcers.