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Background: The onset and progression of type 1 diabetes mellitus (T1DM) is closely related to autoimmunity. Effective monitoring of the immune system and developing targeted therapies are frontier fields in T1DM treatment. Currently, the most available tissue that reflects the immune system is peripheral blood mononuclear cells (PBMCs). Thus, the aim of this study was to identify key PBMC biomarkers of T1DM.Methods: Common differentially expressed genes (DEGs) were screened from the Gene Expression Omnibus (GEO) datasets GSE9006, GSE72377, and GSE55098, and PBMC mRNA expression in T1DM patients was compared with that in healthy participants by GEO2R. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interaction (PPI) network analyses of DEGs were performed using the Cytoscape, DAVID, and STRING databases. The vital hub genes were validated by reverse transcription-polymerase chain reaction using clinical samples. The disease-gene-drug interaction network was built using the Comparative Toxicogenomics Database (CTD) and Drug Gene Interaction Database (DGIdb).Results: We found that various biological functions or pathways related to the immune system and glucose metabolism changed in PBMCs from T1DM patients. In the PPI network, the DEGs of module 1 were significantly enriched in processes including inflammatory and immune responses and in pathways of proteoglycans in cancer. Moreover, we focused on four vital hub genes, namely, chitinase-3-like protein 1 (CHI3L1), C-X-C motif chemokine ligand 1 (CXCL1), matrix metallopeptidase 9 (MMP9), and granzyme B (GZMB), and confirmed them in clinical PBMC samples. Furthermore, the disease-gene-drug interaction network revealed the potential of key genes as reference markers in T1DM.Conclusion: These results provide new insight into T1DM pathogenesis and novel biomarkers that could be widely representative reference indicators or potential therapeutic targets for clinical applications.

Background Time in range (TIR), a novel proxy measure of glucose control, is found closely related to diabetic microangiopathy and some other chronic complications, but the correlation between TIR and lower limb angiopathy has not been studied yet. Our purpose is to explore the relationship between TIR and abnormal ankle-brachial index(ABI) in type 2 diabetes. Methods We retrospectively collected patients’ information from the database and performed cross-sectional analysis. A total of 405 type 2 diabetes patients were enrolled in this study. ABI was measured and patients were stratified into low, normal, and high groups according to ≤ 0.9, > 0.9 and Results The overall prevalence of abnormal ABI was 20.2% (low 4.9% and high 15.3%). TIR was lower in patients with abnormal ABI values (P = 0.009). The prevalence of abnormal ABI decreased with increasing quartiles of TIR (P = 0.026). Abnormal ABI was negatively correlated with TIR and positively correlated with hypertension, age, diabetes duration, UREA, Scr, ACR, TAR, MBG, and M values (P Conclusions In type 2 diabetes patients, abnormal ABI is associated with lower TIR, and the correlation is stronger than that with HbA1C. Therefore, the role of TIR should be emphasized in the evaluation of lower limb vascular diseases.

AimsThe aim of this retrospective single-center is to research the relationship between time in range(TIR), an important novel metric of glycemic control, assessed with continuous glucose monitoring(CGM) and brachial-ankle pulse wave velocity(BaPWV), a unique index of systemic arterial stiffness in type 2 diabetes.MethodsStudy participants included 469 hospitalized patients with type 2 diabetes and no history of serious cardiovascular disease who underwent CGM and BaPWV measurements. TIR of 3.9-10.0 mmol/L was evaluated with CGM. BaPWV was measured by non-invasive arteriosclerosis detector and high baPWV was defined as a mean baPWV≧1800m/s. The spearman correlation and the partial correlation analysis were applied to analyze the correlation between TIR and baPWV. The binary logistic regression was used to examine the independent association of TIR and high BaPWV.ResultsThe presence of high baPWV was 32.2%. Compared with patients of low baPWV, those with high baPWV had significantly reduced TIR(PConclusionTIR is correlated with BaPWV independent of HbA1c in patients with type 2 diabetes, confirming a link between TIR and arterial stiffness.

Background. Diaphanous related formin 1 (DIAPH1) is a novel component of advanced glycation end product (AGE) signal transduction that was recently found to participate in diabetes-related disorders, obesity, and androgen hormones. We investigated whether plasma DIAPH1 levels were a potential prognostic predictor for polycystic ovary syndrome (PCOS). Methods. The levels of circulating plasma DIAPH1 and indicators of glucose, insulin, lipid metabolism, liver enzymes, kidney function, sex hormones, and inflammation were measured in 75 patients with PCOS and 77 healthy participants. All of the participants were divided into normal-weight (NW) and overweight/obese (OW) subgroups. Statistical analyses were performed with R studio. Results. PCOS patients manifested hyperandrogenism, increased luteinizing hormone/follicle-stimulating hormone (LH/FSH), and accumulated body fat and insulin resistance. Plasma DIAPH1 levels were significantly decreased in women with PCOS compared to control participants, and DIAPH1 levels were distinctly reduced in OW PCOS compared to OW control subjects ( P < 0.001 ). DIAPH1 levels correlated with fasting blood glucose (FBG), total cholesterol (TC), the homeostasis model assessment of β-cell function (HOMA-β), and LH/FSH in all participants (FBG: r = 0.351 , P < 0.0001 ; TC: r = 0.178 , P = 0.029 ; HOMA-β: r = − 0.211 , P = 0.009 ; LH/FSH: r = − 0.172 , P = 0.040 ). Multivariate logistic regression analysis revealed that plasma DIAPH1 levels were an independent risk factor for PCOS. A model containing DIAPH1, BMI, FBG, and testosterone was constructed to predict the risk of PCOS, with a sensitivity of 92.0% and a specificity of 80.9%. A nomogram was constructed to facilitate clinical diagnosis. Conclusions. These findings suggest the association of plasma DIAPH1 with glucose metabolism, insulin resistance, and sex hormones and support DIAPH1 as a potential predictive factor for PCOS.

The imbalance of gut microbiota has been linked to manifold endocrine diseases, but the association with Graves’ disease (GD) is still unclear. The purpose of this study was to investigate the correlation between human gut microbiota and clinical characteristics and thyroidal functional status of GD. 14 healthy volunteers (CG) and 15 patients with primary GD (HG) were recruited as subjects. 16SrDNA high-throughput sequencing was performed on IlluminaMiSeq platform to analyze the characteristics of gut microbiota in patients with GD. Among them, the thyroid function of 13 patients basically recovered after treatment with anti-thyroid drugs (oral administration of Methimazole for 3–5 months). The fecal samples of patients after treatment (TG) were sequenced again, to further explore and investigate the potential relationship between dysbacteriosis and GD. In terms of alpha diversity index, the observed OTUs, Simpson and Shannon indices of gut microbiota in patients with GD were significantly lower than those in healthy volunteers (P

Aims Coronavirus disease (COVID-19), also referred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is instigated by a novel coronavirus. The disease was initially reported in Wuhan, China, in December 2019. Diabetes is a risk factor associated with adverse outcomes. Herein, our objective was to investigate the characteristics of laboratory findings of type 2 diabetes mellitus (T2DM) patients infected with SARS-CoV-2. Methods This was a retrospective study and included 80 T2DM patients of Jinling Hospital from 2010 to 2020, as well as 76 COVID-19 patients without T2DM and 55 COVID-19 patients with T2DM who were treated at Huoshen hill Hospital from February 11 to March 18, 2020. We then compared the differences in laboratory test results between the three groups. Results The levels of lymphocytes, uric acid (UA), and globulin in the T2DM group were significantly higher. In contrast, C-reactive protein (CRP), creatinine, and lactic dehydrogenase (LDH)levels were lower than those in the COVID-19 (p 0.05). Conclusion T2DM patients infected with SARS-CoV-2 showed decreased levels of body mass index (BMI), lymphocytes, UA, and albumin, and increased CRP levels. The decreased BMI, UA, and albumin levels may be associated with oxidative stress response and nutritional consumption. The decreased lymphocyte counts and increased CRP levels may be related to the infection.

Objective. The objective of this study is to investigate the relationship between time in range (TIR), a new metric of continuous glucose monitoring (CGM) and cardiovascular autonomic neuropathy (CAN) in individuals with type 2 diabetes mellitus (T2DM). Methods. A total of 349 individuals with T2DM were enrolled in this study. Evaluating by the standard cardiac autonomic reflex tests (CARTs), there were 228 diabetic individuals without cardiovascular autonomic neuropathy (without confirmed CAN) including absent CAN (n=83 cases) and early CAN (n=145 cases) and 121 diabetic individuals complicated with cardiovascular autonomic neuropathy (CAN) including definite CAN (n=109 cases) and severe CAN (n=12 cases). All patients underwent 3-day CGM. TIR is defined as the time percent during a 24-hour period when the glucose is in the range of 3.9-10 mmol/L. The Spearman analysis was used to analyze the correlation between TIR and CART parameters, total CAN score. The logistic regression was applied to analyze the relationship between TIR and CAN by adjusting for the age, duration of diabetes, sex, lipid situation, serum creatinine, body mass index, blood pressure, HbA1c (%), and other glycemic variability (GV) metrics. Results. The total presence of CAN was 34.67% (definite CAN 31.23% and severe CAN 3.44%). Patients with more severe CAN had lower TIR (P<0.001). With increasing quartiles of TIR, the presence of CAN by severity declined (P<0.05). TIR is inversely correlated with total score of CAN (P<0.001) and positively associated with heart rate variation during the lying to standing, Valsalva maneuver, and deep breathing (P<0.05). The logistic regression found a robust association between TIR and CAN independent of HbA1c and GV metrics. Conclusion. TIR is associated with the presence of CAN independent of HbA1c and GV metrics in Chinese type 2 diabetes.

Aims/Introduction Hypertension is one of the most significant risk factors for diabetes. The present study aimed to investigate the associations of lipid profiles, including the ratio of low‐density lipoprotein cholesterol (LDL‐C)‐to‐high‐density lipoprotein cholesterol (HDL‐C) and triglyceride (TG) levels, as well as their interactions, with type 2 diabetes in hypertensive patients. Materials and Methods Hypertensive patients without a history of diabetes and hypolipidemic agents were enrolled continuously at the Hypertension Clinic, Zhongshan Hospital, Fudan University (Shanghai, China) from 2014 to 2016. General clinical data, including body mass index, blood pressure, fasting glucose and 2‐h post‐load glucose levels, and lipid profiles, were collected. The LDL‐C/HDL‐C ratio, TG/HDL‐C ratio and TC/HDL‐C ratio were separately calculated. Statistical analyses were carried out by using SPSS software (version 13.0). Results In total, 935 hypertensive patients were included, of which 114 patients (12.2%) were diagnosed with diabetes. After multivariate adjustments, the LDL‐C/HDL‐C ratio and TG levels had the most significant and independent associations with diabetes. In the multivariate logistic regression, the LDL‐C/HDL‐C ratio and TG were independently associated with diabetes. After the interaction variable was included, the LDL‐C/HDL‐C ratio remained independently associated with diabetes, but TG was replaced by TG*LDL‐C/HDL‐C. Conclusions In conclusion, elevated LDL‐C/HDL‐C ratios and TG levels were associated with diabetes in patients with hypertension, with an interactive effect of the LDL‐C/HDL‐C ratio and TG on diabetes in the hypertensive population.

Tripterygium glycosides (TG) has been used to treat a spectrum of inflammatory and autoimmune diseases. Our preliminary studies have shown that TG is effective in the treatment of active Graves' ophthalmopathy (GO).We aimed to compare the efficacy and tolerability of TG with intravenous methylprednisolone (iv.MP) in patients with active moderate-to-severe GO.This study was an observer-masked, single-centre, block-randomised trial. Patients with active moderate-to-severe GO were randomly assigned to receive iv.MP (500 mg once per week for 6 weeks followed by 250 mg per week for 6 weeks) or with TG (20 mg tablet three times per day for 24 weeks). The primary endpoints were the overall response rate and the patients' quality of life at 12 and 24 weeks.In this study, 161 patients were enrolled and randomised from 2015 to 2019. A total of 79 were randomly assigned to receive iv.MP and 82 to receive TG. A greater overall response rate was found in the TG group compared with the iv.MP group at week 24 (90.2% vs 68.4%, P = 0.000). Similarly, the patients' quality of life of the TG group showed a significantly higher response than the iv.MP group at week 24 (89.02% vs 72.15%, P = 0.001). The TG therapy showed a better CAS response than the iv.MP (91.5% vs 70.9% improved, P0.05), and up to 91.2% of patients were inactive. Also, the TG group showed a significantly higher improved rate of diplopia, proptosis, visual acuity, soft tissue involved and the decrease of eye muscle motility than the iv.MP group at week 24. Significantly more patients in the iv.MP group than the TG group experienced adverse events.Compared with iv.MP treatment, TG therapy is more effective and safer for patients with active moderate to severe GO.

AIMS To compare the efficacy and safety of saxagliptin and glimepiride in type 2 diabetes (T2D) patients who are inadequately controlled with metformin monotherapy. MATERIALS AND METHODS In this 48-week, multi-centre, open-label, randomized, parallel trial (NCT02280486, clinicaltrials.gov), a total of 388 T2D patients were randomized 1:1 to saxagliptin or glimepiride groups. The primary endpoint was achievement of HbA1c

Graves' orbitopathy (GO) is a potentially sight-threatening disease for which currently available medical therapy is not reliably successful. Mycophenolate mofetil (MMF) is a selective immunosuppressant used widely in many autoimmune diseases. Preliminary studies have shown that MMF is effective in the treatment of active GO.To evaluate the efficacy and safety of MMF in patients with active moderate-to-severe GO.One hundred and 74 patients with active moderate-to-severe GO were randomized to receive either MMF or glucocorticoids (GC).The primary outcome was overall response at the 12th and 24th weeks; the outcome assessments included clinical activity score (CAS), soft tissue involvement, pain, visual acuity, proptosis, diplopia and reduction in eye movements. The secondary outcome was changes in those individual parameters. Adverse effects were recorded at each visit.A greater overall response rate was found in the MMF group compared with the GC group at the 24th week (91·3% vs 67·9%, P = 0·000). MMF therapy showed a better CAS response than GC (92·5% vs 70·5% improved, P0·05). Patients treated with MMF showed a significantly improved rate of diplopia and proptosis than patients treated with GC at the 24th week (90·4% and 68·8% improved, respectively). Disease reactivation was not observed in the patients treated with MMF but was observed in five patients after GC therapy. Adverse events occurred in 4 of 80 patients treated with MMF (5%), all of which were mild to moderate. A severe adverse event was only observed in one patient treated with GC but not at all in patients treated with MMF.Compared with GC treatment, MMF therapy is more effective and safer for patients with active moderate-to-severe GO.

The aim of this study was to assess the prevalence of glucose abnormalities in a Chinese Han population with untreated new-onset hypertension. Four hundred and ninety-nine new-onset hypertensive patients without diabetes were enrolled in this study. An abnormal glucose metabolism was diagnosed in 57.1% of the new-onset hypertensive patients without previously diagnosed diabetes. Stratified by age, the prevalence of diabetes and prediabetes were increased with aging. Male sex, advanced age, higher serum triglycerides, and homeostasis model assessment of insulin resistance levels were all significantly associated with the increased risks of pre-diabetes or diabetes in new-onset hypertensive patients when analyzed by the logistic regression analysis.

Protein tyrosine phosphatase (PTP)- 1B, encoded by the PTPN1 gene, negatively regulates insulin signaling by dephosphorylating the phosphotyrosine residues of the insulin receptor kinase activation segment. Several rare single nucleotide polymorphisms (SNP) have been linked to diseases accompanying insulin resistance such as Type 2 diabetes, obesity, and dyslipidemia in different populations.To investigate whether PTP-1B SNP are associated with hypertension and hypertension-related metabolic traits in Chinese subjects.A total of 239 Chinese patients with hypertension and 141 non-hypertensive subjects were screened. The genotypes of PTP-1B gene polymorphisms were determined by PCR-restriction fragment length polymorphism methods.The case-control study showed associations between the frequencies of T allelic g54281 TA and A allele of I5/37CA and hypertension (p0.0001, p=0.0371, respectively). In addition, significant associations were observed between the IVS6+G82A polymorphism and waist circumference, total cholesterol, and LDL-cholesterol levels in hypertensive patients (p=0.0005 approximately 0.0260). And g54281 T allele was associated with higher plasma triglyceride (p=0.0390) and LDL-cholesterol concentration (p=0.0141), while g58585 TC was associated with body mass index (BMI) (p=0.0308), waist circumference (p=0.0216), and homeostasis model assessment of insulin resistance (p=0.047). Multivariate logistic regression analysis showed that T allele carriers of g54281TA and A allele carriers of I5/37CA had higher risks of hypertension independent of age, gender, BMI, glucose levels, and lipids profiles [odds ratio (OR): 1.79, 95% confidence interval (CI): 1.09- 2.96, p=0.02; OR: 1.66, 95% CI: 1.13-2.44, p=0.01, respectively].PTP-1B polymorphisms contribute to pathogenesis of hypertension in Chinese subjects and PTP-1B SNP may be involved in the development of several features including dyslipidemia and obesity in hypertensive subjects.

This paper presents a detailed study of fractal-based methods for texture characterization of mammographic mass lesions and architectural distortion. The purpose of this study is to explore the use of fractal and lacunarity analysis for the characterization and classification of both tumor lesions and normal breast parenchyma in mammography. We conducted comparative evaluations of five popular fractal dimension estimation methods for the characterization of the texture of mass lesions and architectural distortion. We applied the concept of lacunarity to the description of the spatial distribution of the pixel intensities in mammographic images. These methods were tested with a set of 57 breast masses and 60 normal breast parenchyma (dataset1), and with another set of 19 architectural distortions and 41 normal breast parenchyma (dataset2). Support vector machines (SVM) were used as a pattern classification method for tumor classification. Experimental results showed that the fractal dimension of region of interest (ROIs) depicting mass lesions and architectural distortion was statistically significantly lower than that of normal breast parenchyma for all five methods. Receiver operating characteristic (ROC) analysis showed that fractional Brownian motion (FBM) method generated the highest area under ROC curve (A z = 0.839 for dataset1, 0.828 for dataset2, respectively) among five methods for both datasets. Lacunarity analysis showed that the ROIs depicting mass lesions and architectural distortion had higher lacunarities than those of ROIs depicting normal breast parenchyma. The combination of FBM fractal dimension and lacunarity yielded the highest A z value (0.903 and 0.875, respectively) than those based on single feature alone for both given datasets. The application of the SVM improved the performance of the fractal-based features in differentiating tumor lesions from normal breast parenchyma by generating higher A z value. FBM texture model is the most appropriate model for characterizing mammographic images due to self-affinity assumption of the method being a better approximation. Lacunarity is an effective counterpart measure of the fractal dimension in texture feature extraction in mammographic images. The classification results obtained in this work suggest that the SVM is an effective method with great potential for classification in mammographic image analysis.

Our previous study indicated that lapatinib induces p27-dependent G(1) arrest through both transcriptional and post-translational mechanisms. Using miRNA microarray technology and quantitative RT-PCR, we further investigated the potential miRNAs that involved in p27 upregulation and Her-2 signaling pathway alteration with lapatinib treatment. A subset of 7 miRNAs was significantly affected in both 0.5 µM and 2.0 µM and 24 h and 48 h lapatinib treatment. Among them, only miR-1470, miR-126, and miR-1208 were identified in the Her-2 pathway after KEGG pathway analysis. However, luciferase reporter assay confirmed that miR-1470 directly recognized the 3'-untranslated region of c-jun transcripts, which was consistent with TargetScan analysis. miR-1470 significantly decreased c-jun expression, thus miR-1470 may repressc-jun activation of cyclinD1 expression, and consequently promoted the upregulation of p27, a key molecule in the cell cycle arrest. Taken together, the present study provided the first evidences that miR-1470 mediated lapatinib induced p27 upregulation by targeting c-jun.

Background and Aim Atypical coronary artery disease (ACAD) is characterized by atypical angina pectoris or silent myocardial ischemia. However, conventional diagnostic techniques are insufficient to identify this subtype of coronary atherosclerotic pathology, and specific and sensitive markers for diagnosing ACAD are still currently lacking. The aim of the present study is to identify a novel serum microRNA (miRNA) expression profile of ACAD patients and evaluate its clinical diagnostic value. Patients and Methods 127 patients who were diagnosed with ACAD and 54 age-matched controls were enrolled in this study. An initial screen of miRNA expression was performed in serum samples from 35 patients and 20 controls using TaqMan Low Density Array. A stem-loop quantitative reverse-transcription PCR (RT-qPCR) assay was conducted in the training and validation sets to confirm the levels of the altered miRNAs in 122 patients with ACAD and 68 controls. In addition, the potential target genes of the altered miRNAs were predicted using bioinformatics methods. Results The TaqMan low density array and RT-qPCR analysis identified four serum miRNAs including miR-487a, miR-502, miR-208 and miR-215 that were significantly increased, while one miRNA, miR-29b, that was significantly decreased in ACAD patients compared with normal controls (P

Relationship between the p27Kip1 (here after referred to as p27) V109G polymorphism and cancer risk has been extensively studied; however, results from different studies were not fully consistent. Therefore, we carried out a meta-analysis to comprehensively assess the correlation between the p27V109G polymorphism and the cancer risk. Articles on the relationship of the p27V109G polymorphism with cancer risk were searched from Medline, Pub Med, and Web of science databases. A total of eight eligible studies with 3591 cases and 3799 controls were included in this meta-analysis. Overall, it seemed that the G allele was not associated with the elevated cancer risk (pooled odds ratio [OR]=0.98, 95% confidence interval [CI]: 0.88-1.09, p=0.68, fixed effects). Analyses in different populations revealed that no statistically significant associations between the G allele and cancer risk were demonstrated in Caucasians or Asians. When analyzed in different types of cancer that, from two studies, the G allele was found to be associated with a decreased risk of prostate cancer in a dominant genetic model (pooled OR=0.60, 95% CI=0.36-0.98, p=0.04, fixed effects), but did not alter the breast cancer risk from four studies. In conclusion, this meta-analysis indicated that the p27V109G polymorphism did not correlate with the overall cancer risk in the general population.

The development and clinical application of TK domain inhibitors (TKIs) provide important insights into the broader field of cancer-targeted therapies. To discuss the recent advances in the atomic level understanding of EGFR TK domain mutations, we aim at highlighting the current and future importance of these studies on malignancies where the TK domain is improperly activated. The analysis is conducted on published TK domain crystal structures deposited in the Protein Data Bank, or homology structures generated by homology modeling and AutoDock 4.2 software using the program O. Mutations in exon 19 are the most common pathogenic mutations, so the crystal structures with these mutations are analyzed and compared in detail. In addition, we demonstrate how these crystal structures of EGFR conformation with TK domain mutations and those binding with small molecule inhibitors unveil the active or inactive mechanisms. As to the increasing resistance to the TKI, we summarize the progress on overcoming this challenge. Simultaneously, we predict the structure of BIKW-2992 binding to EGFR and compare it with the validated structure of HKI-272. It is hoped that a more accurate resistance mechanism would be found. In brief, we believe that this research will provide insights into EGFR targeted therapies.

There is growing evidence that chemerin, a novel adipokine elevated in obesity and metabolic syndromes, plays a crucial role in advanced atherosclerosis. This study aimed to determine the chemerin levels in diabetes and evaluate the effects of increased chemerin on early atherosclerosis. A total of 245 newly diagnosed diabetic patients and 148 age-matched, healthy, normal glucose tolerant (NGT) controls were enrolled. Anthropometric measurements and plasma parameters were examined, including body mass index (BMI), waist circumference, blood pressure, glucose, lipid profiles, inflammation markers, adipokines, and cell adhesion molecules. Vascular healthy was measured with brachial flow-mediated dilatation (FMD) and carotid intima-media thickness (IMT). Compared with NGT controls, plasma chemerin levels were higher in diabetic patients (P