Near Infrared Light-Triggered Photocatalytic Decaging for Remote-Controlled Spatiotemporal Activation in Living Mice.

Spatiotemporal manipulation of biological processes in living animals using noninvasive, remote-controlled stimuli is a captivating but challenging endeavor. Herein, we present the development of a biocompatible photocatalytic technology termed CAT-NIR, which uses external near infrared light (NIR, 740 nm) to trigger decaging reactions in living mice. The Os(II) terpyridine complex was identified as an efficient NIR photocatalyst for promoting deboronative hydroxylation reactions via superoxide generation in the presence of NIR light, resulting in the deprotection of phenol groups and the release of bioactive molecules under living conditions. The validation of the CAT-NIR system was demonstrated through the NIR-triggered rescue of fluorophores, prodrugs as well as biomolecules ranging from amino acids, peptides to proteins. Furthermore, by combining genetic code expansion and computer-aided screening, CAT-NIR could regulate affibody binding to the cell surface receptor HER2, providing a selective cell tagging technology through external NIR light. In particular, the tissue-penetrating ability of NIR light allowed for facile prodrug activation in living mice, enabling noninvasive, remote-controlled rescue of drug molecules. Given its broad adaptability, this CAT-NIR system may open new opportunities for manipulating the functions of bioactive molecules in living animals using external NIR light with spatiotemporal resolution.

Association of circulating proprotein convertase subtilisin/kexin type 9 levels and the risk of incident type 2 diabetes in subjects with prediabetes: a population-based cohort study.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates cholesterol metabolism by targeting the low-density lipoprotein receptor. Recent studies have shown that circulating PCSK9 is associated with glucose homeostasis and insulin resistance. The aim of this study was to examine the association of circulating PCSK9 levels and risk for the development of type 2 diabetes in individuals with prediabetes. METHODS: A population-based prospective study was conducted among 4205 Chinese subjects with prediabetes (average age 56.1 ± 7.5 years). Incident type 2 diabetes was diagnosed according to 2010 American Diabetes Association criteria. Circulating PCSK9 levels were measured using a commercially available enzyme-linked immunosorbent assay (ELISA). The association of circulating PCSK9 levels with the risk of incident type 2 diabetes was assessed by Cox regression analysis. RESULTS: During a median follow-up period of 3.1 years, 568 subjects developed type 2 diabetes. Baseline circulating PCSK9 levels were significantly higher in female subjects developing incident type 2 diabetes than in those not developing incident type 2 diabetes (p < 0.001). In female subjects, the risk of incident type 2 diabetes was significantly higher in the highest PCSK9 quartile group (hazard ratio 2.16; 95% confidence interval 1.16-4.04) than in the lowest quartile group after adjustments for age, body mass index, waist circumference, C-reactive protein, γ-glutamyltransferase, triglycerides, low-density lipoprotein cholesterol, systolic blood pressure, and homeostatic model assessment of insulin resistance score. No significant association was observed between PCSK9 and incident type 2 diabetes in male subjects. CONCLUSION: Elevated circulating PCSK9 levels are associated with an increased incidence of type 2 diabetes in female subjects with prediabetes.

Circulating heat shock protein 27 as a novel marker of subclinical atherosclerosis in type 2 diabetes: a cross-sectional community-based study.

BACKGROUND: Heat shock protein 27 (HSP27) has been proposed as a vital protective factor in atherosclerosis. The objective of the present study was to evaluate the association between circulating HSP27 and carotid intima-media thickness (IMT) in individuals with type 2 diabetes and to determine whether HSP27 represents an independent marker of subclinical atherosclerosis in this patient population. METHODS: We performed a cross-sectional community-based study in 186 Chinese subjects with a median duration of type 2 diabetes of 8.2 years who underwent ultrasound carotid IMT measurement. Serum HSP27 levels were assessed by ELISA. RESULTS: Serum HSP27 levels were significantly higher in the IMT (+, > 1.0 mm) group than in the IMT (-, ≤1.0 mm) group, with the median values of 8.80 ng/mL (5.62-12.25) and 6.93 ng/mL (4.23-9.60), respectively (P = 0.006). The discriminative value of HSP27 to evaluate IMT was 7.16 ng/mL and the area under the curve was 0.72 (95%CI = 0.64-0.80, P = 0.0065). Spearman's rank correlation analysis demonstrated that the concentrations of circulating HSP27 were positively associated with carotid IMT (r = 0.198, P = 0.007) and blood urea nitrogen (r = 0.170, P < 0.05). Furthermore, in the logistic model, serum HSP27 levels were found to be independent predictors for carotid IMT in type 2 diabetic patients after adjustment for onset age of diabetes, blood pressure, total cholesterol and C-reactive protein (OR = 1.085, P = 0.022). CONCLUSIONS: Circulating HSP27, positively correlates with carotid IMT, is an independent predictor for early atherosclerotic changes in diabetes, and may represent a novel marker of subclinical atherosclerosis in type 2 diabetes.

Iron-Catalyzed Direct Oxidative Alkylation and Hydroxylation of Indolin-2-ones with Alkyl-Substituted N-Heteroarenes.

Presented herein is the first direct alkylation and hydroxylation reaction between two different C(sp3 )-H bonds, indolin-2-ones and alkyl-substituted N-heteroarenes, through an oxidative cross-coupling reaction. The reaction is catalyzed by a simple iron salt under mild ligand-free and base-free conditions. The reaction is environmentally benign, employs air (molecular oxygen) as the terminal oxidant and oxygen source for the synthesis of O-containing compounds, and produces only water as the byproduct.

Elevated circulating cathepsin S levels are associated with metabolic syndrome in overweight and obese individuals.

OBJECTIVE: Cathepsin S is highly expressed in subcutaneous and visceral adipose tissue. Cathepsin S correlates with central obesity and contributes to the formation and progression of atherosclerosis. Here, we sought to evaluate the association of serum cathepsin S with metabolic syndrome (MS) in overweight and obese Chinese adults. METHODS: We evaluated serum cathepsin S levels in a cross-sectional sample of 781 overweight and obese Chinese adults by ELISA. Glucose, insulin, lipid profile, inflammatory markers, and adipokines were also measured. RESULTS: Cathepsin S was significantly associated with BMI, waist circumference, waist-to-hip ratio, fasting glucose, fasting insulin, the homeostatic model assessment of insulin resistance (HOMA-IR), systolic blood pressure, C-reactive protein (CRP), triglycerides, and HDL cholesterol (all P < 0.05). Plasma cathepsin S levels increased significantly (P = 0.045 for trend) with increasing numbers of MS components after adjustment for potential confounders. In the highest cathepsin S quartile, the MS risk was significantly higher (odds ratio 2.30; 95% confidence interval, 1.89-2.78) than in the lowest quartile after adjustment for age, gender, alcohol consumption, smoking, education, physical activity, self-reported CVD, and family history of diabetes. This association remained strong (odds ratio 1.97; 95% confidence interval, 1.72-2.48) after controlling further for CRP, adiponectin, HOMA-IR, and BMI. CONCLUSIONS: Elevated circulating cathepsin S concentrations are strongly and independently associated with MS in overweight and obese Chinese adults. Prospective studies are needed to establish the role of cathepsin S in the development of MS.

Anti-interleukin-1 therapy has mild hypoglycaemic effect in type 2 diabetes.

The aim of this study was to systematically evaluate the efficacy and safety of anti-interleukin-1 therapy for type 2 diabetes. A literature search of PubMed and Embase for available trials on anti-interleukin-1 therapy in type 2 diabetes was performed. The baseline characteristics, changes in HbA1c and other metabolic parameters, and adverse events were extracted from included randomized controlled trials (RCTs) and were analysed with Review Manager. Mean differences (MDs) and 95% confidence intervals (Cis) were calculated to measure differences in metabolic parameters. Odds ratio and 95% CIs were calculated for adverse event rates. Five RCTs were included in the current meta-analysis with 357 subjects undergoing anti-interleukin-1 therapy (IL-1 receptor antagonist or anti-IL-1beta antibody) and 221 controls who received placebo. The HbA1c decrement (%) of anti-interleukin-1 group was significantly higher than that of the placebo group (MD = 0.23; 95% CI, -0.39 to -0.07; P = .005). AUC of C-peptide was improved also (MD = 14.55; 95% CI, 1.81-27.28; P = .03) after anti-interleukin-1 intervention. There was no difference in the rate of adverse events (odds ratio,1.16; 95% CI, 0.90-1.49; P = .25) between 2 groups. Anti-interleukin-1 therapy has mild hypoglycaemic effect in type 2 diabetes.

Exogenous kallikrein protects against diabetic nephropathy.

The kallikrein-kinin system has been shown to be involved in the development of diabetic nephropathy, but specific mechanisms are not fully understood. Here, we determined the renal-protective role of exogenous pancreatic kallikrein in diabetic mice and studied potential mechanisms in db/db type 2 diabetic and streptozotocin-induced type 1 diabetic mice. After the onset of diabetes, mice were treated with either pancreatic kallikrein (db/db+kallikrein, streptozotocin+kallikrein) or saline (db/db+saline, streptozotocin+saline) for 16 weeks, while another group of streptozotocin-induced diabetic mice received the same treatment after onset of albuminuria (streptozotocin'+kallikrein, streptozotocin'+saline). Db/m littermates or wild type mice were used as non-diabetic controls. Pancreatic kallikrein had no effects on body weight, blood glucose and blood pressure, but significantly reduced albuminuria among all three groups. Pathological analysis showed that exogenous kallikrein decreased the thickness of the glomerular basement membrane, protected against the effacement of foot process, the loss of endothelial fenestrae, and prevented the loss of podocytes in diabetic mice. Renal fibrosis, inflammation and oxidative stress were reduced in kallikrein-treated mice compared to diabetic controls. The expression of kininogen1, tissue kallikrein, kinin B1 and B2 receptors were all increased in the kallikrein-treated compared to saline-treated mice. Thus, exogenous pancreatic kallikrein both prevented and ameliorated diabetic nephropathy, which may be mediated by activating the kallikrein-kinin system.

Cross-sectional analysis of serum calcium levels for associations with left ventricular hypertrophy in normocalcemia individuals with type 2 diabetes.

BACKGROUND: Left ventricular hypertrophy (LVH) is prevalent in patients with type 2 diabetes mellitus (T2DM). Recent studies show that an increase in albumin-adjusted serum calcium level is associated with an elevated risk of T2DM. We speculate that increased serum calcium levels in T2DM patients are related to LVH prevalence. METHODS: In this echocardiographic study, 833 normocalcemia and normophosphatemia patients with T2DM were enrolled. The associations between serum calcium and metabolic parameters, left ventricular mass index (LVMI), as well as the rate of LVH were examined using bivariate linear correlation, multivariate linear regression and logistic regression, respectively. The predictive performance of serum calcium for LVH was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: Patients with LVH have significantly higher serum calcium than those without LVH. Serum calcium was positively associated with total cholesterol, triglycerides, low-density lipoprotein cholesterol, serum uric acid, HOMA-IR and fasting plasma glucose. Multivariate linear regression analysis demonstrated that serum calcium was independently associated with LVMI (p < 0.001). In comparison with patients in the lowest serum calcium quartile, the odds ratio (OR) for LVH in patients in the highest quartile was 2.909 (95% CI 1.792-4.720; p < 0.001). When serum calcium was analyzed as a continuous variable, per 1 mg/dl increase, the OR (95% CI) for LVH was [2.400 (1.552-3.713); p < 0.001]. Serum calcium can predict LVH (AUC = 0.617; 95% CI (0.577-0.656); p < 0.001). CONCLUSIONS: Albumin-adjusted serum calcium is associated with an increased risk of LVH in patients with T2DM.

Association of genetic predisposition to obesity with type 2 diabetes risk in Han Chinese individuals.

AIMS/HYPOTHESIS: Obesity is a major risk factor for type 2 diabetes, but little is known about the contribution of BMI-associated loci to type 2 diabetes risk in East Asian populations. METHODS: In this study, 30 known BMI-associated variants and a genetic risk score (GRS) calculated by summing the BMI-increasing alleles of these variants were tested for associations with type 2 diabetes and related glycaemic traits in 1,873 cases of type 2 diabetes and 1,839 controls in Han Chinese individuals. Logistic and linear regression analyses were performed to determine the association with type 2 diabetes risk or related glycaemic traits, respectively, under an additive model with or without adjustment for BMI. RESULTS: The GRS was significantly associated with increased BMI (ß [SE] 0.070 [0.016]; p = 1.33 × 0(-5)) in the overall population. Each additional BMI-increasing allele in the GRS increased type 2 diabetes risk by 1.029-fold (95% CI 1.008, 1.050; p = 0.0056) without adjustment for BMI, and the association was slightly attenuated after adjustment for BMI (OR 1.022; 95% CI 1.002, 1.043; p = 0.035). In non-diabetic controls, the GRS was also associated with HOMA of beta cell function (HOMA-B) with adjustment for BMI (ß [SE] -0.876 [0.345]; p = 0.011). Notably, the association of GRS with type 2 diabetes was abolished after adjusting for HOMA-B (OR 1.012; 95% CI 0.986, 1.039; p = 0.380). CONCLUSIONS/INTERPRETATION: Our results suggested that genetic predisposition to obesity leads to increased risk of type 2 diabetes, independent of BMI and partly through impaired beta cell function.

Serum lipocalin-2, cathepsin S and chemerin levels and nonalcoholic fatty liver disease.

Several novel circulating adipokines are associated with insulin resistance and inflammation. Little information exists in NAFLD about three recently recognized adipokines lipocalin-2, cathepsin S and chemerin. To assess the relationship between serum lipocalin-2, cathepsin S and chemerin levels and the development of non-alcoholic fatty liver in Chinese subjects, we measured serum lipocalin-2, cathepsin S and chemerin levels in 903 Chinese subjects by ELISA. Among the study population, 436 patients are with B-mode ultrasound-proven NAFLD and 467 controls. Levels of lipocalin-2, but not cathepsin S and chemerin, were significantly elevated in NAFLD versus control [lipocalin-2, 89.67 ± 4.47 vs. 68.70 ± 3.65 ng/mL (p < 0.001)]. After stepwise linear regression analysis adjusting for potential cofounders, further revealed that serum lipocalcin-2 was an independent predictor of NAFLD in whole cohort (standardized ß = 0.114, t = 2.347, p = 0.02). Lipocalin-2 levels correlated with insulin resistance (homeostasis model assessment of insulin resistance) and inflammation (CRP) in whole cohorts and NAFLD, whereas cathepsin S and chemerin only correlated positively with insulin resistance and inflammation in whole cohorts. Our results indicated that circulating lipocalin-2, produced by adipocytes, are elevated and may contribute to the development of NAFLD. Serum lipocalin-2, which correlates with inflammation and insulin resistance, may have a direct pathogenic link to disease progression.

Association of lipid profiles and the ratios with arterial stiffness in middle-aged and elderly Chinese.

BACKGROUND: Serum lipids and the ratios are known to be associated with the cardiovascular diseases (CVD). However, the associations of serum lipids and the ratios related to arterial stiffness are unclear. We sought to compare the strength of these serum lipids and the ratios with arterial stiffness assessing by brachial-ankle pulse wave velocity (baPWV) in the middle-aged and elderly Chinese subjects. METHODS: A total number of 1133 Chinese aged from 50 to 90 years old were recruited from Shanghai downtown district. The serum lipids, baPWV and major cardiovascular risk factors of the participants were measured. RESULTS: Participants with high baPWV exhibited higher levels of non-HDL-c, TC/HDL-c, TG/HDL-c, LDL-c/HDL-c, and non-HDL-c/HDL-c, while HDL-c worked in the opposite direction (all P<0.05). In addition, TC, TG, LDL-c, non-HDL-c, TC/HDL-c, TG/HDL-c, LDL-c/HDL-c, and non-HDL-c/HDL-c had a positive relationship with the baPWV value, while HDL-c was on the contrary (all P <0.05). Finally, individuals with high non-HDL-c/HDL-c (OR 1.71, 95% CI 1.06-2.55, P = 0.013) and low HDL-c (OR 0.57, 95% CI 0.35-0.96, P = 0.024) were seem to be at high risk of arterial stiffness. CONCLUSIONS: As a risk indicator, non-HDL-c/HDL-c, which could be readily obtained from routine serum lipids, was significantly associated with baPWV. Non-HDL-c/HDL-c was superior to traditional lipid variables for estimating arterial stiffness in the middle-aged and elderly Chinese population.

The anorexic effect of Ex4/Fc through GLP-1 receptor activation in high-fat diet fed mice.

Exendin-4 (Ex4), a peptide initially found in the saliva of the Gila monster, can activate the signaling pathway of the incretin hormone glucagon-like peptide-1 (GLP-1) through the GLP-1 receptor (GLP-1R). We previously reported that a chimera protein consisting of Ex4 and mouse IgG heavy chain constant regions (Ex4/Fc) can exert biological effects of GLP-1, such as improving glycemic control and ameliorating manifestations in diabetic mice. The aim of this study was to determine whether Ex4/Fc is effective in modulating energy homeostasis in mice. Our results showed that in vivo expression of Ex4/Fc by intramuscular injection of the plasmid encoding Ex4/Fc followed by local electroporation effectively decreased food intake in the mice on high-fat diet (HFD) feeding. In addition, the reduced energy intake was associated with the decreased excrements from the Ex4/Fc-treated HFD mice but not the Fc control mice. Remarkably, the Ex4/Fctreated HFD mice displayed significantly lower triglyceride (TG) levels when compared with the control mice. Interestingly, while the leptin levels were not changed, the circulating ghrelin levels were higher in Ex4/Fc mice than those in the Fc control mice. These results suggested that Ex4/Fc can improve energy metabolism and lipid metabolism through GLP-1R in mice under excessive nutrition conditions.

[A clinical analysis of thyrotropin-secreting pituitary adenomas in 20 patients].

OBJECTIVE: To explore the clinical characteristics of thyrotropin-secreting pituitary adenomas. METHODS: A total of 20 patients with thyrotropin-secreting pituitary adenomas hospitalized in Shanghai Huashan Hospital from 2006 to 2013 were enrolled in the study. The clinical features, hormone levels, imaging findings, treatment and follow-up data were reviewed and analyzed. RESULTS: Most of the patients were young and middle-aged with (40.0 ± 14.5) years old. The disease duration varied from 1 month to 15 years. Among them, 13 cases (65%) presented with thyrotoxicosis and/or thyroid goiters and 9 (45%) presented with symptoms of intracranial compression. All patients had unsuppressed levels of thyroid stimulating hormone (TSH) with elevated levels of thyroid hormones. Pituitary lesions were found in all patients by neuroimaging. Pituitary adenomectomy, and/or somatostatin analogs and/or radiotherapy were applied in all patients after definitive diagnosis. Restored euthyroidism and shrinks pituitary adenomas with no progression were observed in 18 patients. Relapse was found in 1 patient and another patient was lost to follow up. CONCLUSIONS: Thyrotropin-secreting pituitary adenomas mainly present with thyrotoxicosis and/or pituitary tumor. Comprehensive therapy, including adenomectomy, somatostatin analogues and radiotherapy, is often needed for the management.

Activity-Based Protein Profiling of RHBDL4 Reveals Proteolysis of the Enzyme and a Distinct Inhibitor Profile.

Rhomboid proteases have fascinated scientists by virtue of their membrane-embedded active sites and proposed involvement in physiological and disease pathways. The human rhomboid protease RHBDL4 has generated particular interest due to its role in endoplasmic reticulum-associated protein degradation and upregulation in several cancers; however, chemical tools for studying this enzyme are currently lacking. Here, we describe the development of an activity-based protein profiling (ABPP) assay for RHBDL4. We have employed this assay to determine that human RHBDL4 undergoes proteolytic processing in cells to produce multiple active proteoforms with truncated C-termini. We have also used this assay to identify chemical scaffolds capable of inhibiting RHBDL4 activity and have observed distinct inhibitor preferences between RHBDL4 and a second human rhomboid protease PARL. Our work demonstrates the power of ABPP technology to characterize active forms of enzymes that might otherwise elude detection and the potential to achieve selective inhibition among the human rhomboid proteases.

Characteristics of metabolic inflammatory syndrome among inpatients with type 2 diabetes: A cross-sectional study in China.

BACKGROUND: As meta-inflammation is a common feature for obesity, type 2 diabetes (T2D), nonalcoholic fatty liver disease and atherosclerosis, we have proposed a new concept, metabolic inflammatory syndrome (MIS), to cluster such diseases. We aimed to characterize MIS and explore its association with coronary heart disease (CHD) among T2D inpatients in China. METHODS: A total number of 8344 T2D participants were enrolled. Each component of MIS and metabolic syndrome (MS) was analyzed. Their association with the risk of CHD was assessed using a binary logistic analysis. RESULTS: Among the T2D inpatients, the detection rate of MIS was much higher than that of MS (93.6 % vs. 53.2 %). Among all the components of MIS and MS, carotid atherosclerosis (71.9 %) was most commonly detected, which increased with aging in subgroups. Surprisingly, the most common combination of MIS was with all 4 components in T2D patients, with a constituent ratio of 30.9 %. According to the odds ratios (ORs), MIS was a better predictor of CHD than MS, especially after adjustment for age, sex, smoking, and alcohol consumption (adjusted OR for MIS: 3.083; for MS: 1.515). The presence of more components of MIS was associated with a higher detection rate of CHD (P < 0.001). Among all the components of MIS and MS, carotid atherosclerosis best predicted the risk of CHD (adjusted OR: 1.787). CONCLUSIONS: MIS is an independent risk factor for CHD, with a bigger OR value than MS. Carotid atherosclerosis, with the highest detection rate, was the best individual predictor of CHD and thus a critical component of MIS. The concept of MIS represents the understanding of metabolic diseases from the perspective of holistic integrative medicine.

Association of single-nucleotide polymorphisms in the STAT3 gene with autoimmune thyroid disease in Chinese individuals.

The aim of this study was to investigate the association between signal transducer and activator of transcription 3 (STAT3) polymorphisms and autoimmune thyroid diseases and clinical features. We genotyped six single-nucleotide polymorphisms (SNPs) rs1053005, rs2293152, rs744166, rs17593222, rs2291281, and rs2291282 of STAT3 gene in 667 patients with autoimmune thyroid disease (417 Graves' disease (GD) and 250 Hashimoto's thyroiditis (HT)) and 301 healthy controls. The allele A from rs1053005 was significantly less frequent in both GD and HT patients (P = 0.0024, OR = 0.6958, 95%CI = 0.5508-0.8788; P = 0.0091, OR = 0.7013, 95%CI = 0.5397-0.9112, respectively). The AA genotype of rs1053005 was less in GD and HT patients too (P = 0.0025,OR = 0.6278, 95%CI = 0.466-0.847) and (P = 0.0036,OR = 0.601, 95%CI = 0.428-0.843). The allele G from rs17593222 increased the susceptibility to the ophthalmopathy development both in autoimmune thyroid disease (AITD) and GD patients (P = 0.0007, OR = 3.980, 95%CI = 1.871-8.464; P = 0.0081, OR = 3.378, 95%CI = 1.441-7.919, respectively). The allele A and AA genotype of SNP rs1053005 may protect individuals from the susceptibility to AITD and their frequency decreased in AITD patients. In addition, the allele G of rs17593222 may increase the ophthalmopathy risk in AITD patients. Our findings suggest the existence of association between STAT3 gene and AITD, thus adding STAT3 gene to the list of the predisposing genes to AITD.

Low-grade albuminuria is associated with early but not late carotid atherosclerotic lesions in community-based patients with type 2 diabetes.

BACKGROUND: Low-grade albuminuria is associated with cardiovascular risk factors and mortality. Our aim was to investigate the association between low-grade albuminuria and carotid atherosclerotic lesions in community-based patients with type 2 diabetes. METHODS: A cross-sectional study was performed in 475 community-based patients with type 2 diabetes (190 males and 285 females) with normal urinary albumin-to-creatinine ratios (UACR) (< 3.5 mg/mmol) from Shanghai, China. The subjects were stratified into tertiles based on UACR levels (the lowest tertile was UACR ≤ 1.19 mg/mmol, and the highest tertile was UACR ≥ 2 mg/mmol). Carotid intima-media thickness (CIMT), carotid atherosclerotic plaque formation and stenosis were assessed and compared among the three groups based on ultrasonography. The urinary albumin excretion rate was determined as the mean of the values obtained from three separate early morning urine samples. RESULTS: Compared with the subjects with UACR in the lowest tertile, the subjects with UACR in the middle and highest tertiles had greater CIMT values (0.88 ± 0.35 mm, 0.99 ± 0.43 mm and 1.04 ± 0.35 mm, respectively; all p < 0.05) and a higher prevalence of carotid atherosclerotic plaques (25.3%, 39.0% and 46.2%, respectively; all p < 0.05) after adjusting for sex and age. Fully adjusted multiple linear regression and logistic regression analyses revealed that UACR tertiles were significantly associated with elevated CIMT (p = 0.007) and that, compared with the subjects in the first tertile of UACR, those in the second and third tertiles had 1.878- and 2.028-fold risk of carotid plaques, respectively. However, there was no statistical association between UACR tertile and the prevalence of carotid stenosis. CONCLUSIONS: Higher UACR within the normal range was independently associated with early but not late carotid atherosclerotic lesions in community-based patients with type 2 diabetes. Low-grade albuminuria contributes to the risk of carotid atherosclerosis and may be used as an early marker for the detection of atherosclerosis in patients with type 2 diabetes.

Glycemic control among patients in China with type 2 diabetes mellitus receiving oral drugs or injectables.

BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) is increasing rapidly among Chinese adults, and limited data are available on T2DM management and the status of glycemic control in China. We assessed the efficacy of oral antidiabetes drugs (OADs), glucagon-like peptide-1 (GLP-1) receptor agonists, and insulin for treatment of T2DM across multiple regions in China. METHODS: This was a multicenter, cross-sectional survey of outpatients conducted in 606 hospitals across China. Data from all the patients were collected between April and June, 2011. RESULTS: A total of 238,639 patients were included in the survey. Eligible patients were treated with either OADs alone (n=157,212 [65.88%]), OADs plus insulin (n=80,973 [33.93%]), or OADs plus GLP-1 receptor agonists (n=454 [0.19%]). The OAD monotherapy, OAD + insulin, and OAD + GLP-1 receptor agonist groups had mean glycosylated hemoglobin (HbA1c) levels (±SD) of 7.67% (±1.58%), 8.21% (±1.91%), and 7.80% (±1.76%), respectively. Among those three groups, 34.63%, 26.21%, and 36.12% met the goal of HbA1c <7.0%, respectively. Mean HbA1c and achievement of A1c <7.0% was related to the duration of T2DM. CONCLUSIONS: Less than one third of the patients had achieved the goal of HbA1c <7.0%. Glycemic control decreased and insulin use increased with the duration of diabetes.

Chemoproteomic strategy identified p120-catenin glutathionylation regulates E-cadherin degradation and cell migration.

Identification of cysteines with high oxidation susceptibility is important for understanding redox-mediated biological processes. In this report, we report a chemical proteomic strategy that finds cysteines with high susceptibility to S-glutathionylation. Our proteomic strategy, named clickable glutathione-based isotope-coded affinity tag (G-ICAT), identified 1,518 glutathionylated cysteines while determining their relative levels of glutathionylated and reduced forms upon adding hydrogen peroxide. Among identified cysteines, we demonstrated that CTNND1 (p120) C692 has high susceptibility to glutathionylation. Also, p120 wild type (WT), compared to C692S, induces its dissociation from E-cadherin under oxidative stress, such as glucose depletion. p120 and E-cadherin dissociation correlated with E-cadherin destabilization via its proteasomal degradation. Lastly, we showed that p120 WT, compared to C692S, increases migration and invasion of MCF7 cells under glucose depletion, supporting a model that p120 C692 glutathionylation increases cell migration and invasion by destabilization of E-cadherin, a core player in cell-cell adhesion.

Consensus of Chinese experts on strengthening personalized prevention and treatment of type 2 diabetes.

Up to now, there has not yet been guidance or consensus from Chinese experts in the field of personalized prevention and treatment of type 2 diabetes. In view of the above, the endocrinology diabetes Professional Committee of Chinese Non-government Medical Institutions Association, the integrated endocrinology diabetes Professional Committee of the integrated medicine branch of Chinese Medical Doctor Association, and the diabetes education and microvascular complications group of the diabetes branch of the Chinese Medical Association organized relevant experts to discuss and reach the "Chinese expert consensus on strengthening personalized prevention and treatment of type 2 diabetes" for reference in clinical practice.