Correlation between NGS panel-based mutation results and clinical information in colorectal cancer patients.

Early mutation identification guides patients with colorectal cancer (CRC) toward targeted therapies. In the present study, 414 patients with CRC were enrolled, and amplicon-based targeted next-generation sequencing (NGS) was then performed to detect genomic alterations within the 73 cancer-related genes in the OncoAim panel. The overall mutation rate was 91.5 % (379/414). Gene mutations were detected in 38/73 genes tested. The most frequently mutated genes were TP53 (60.9 %), KRAS (46.6 %), APC (30.4 %), PIK3CA (15.9 %), FBXW7 (8.2 %), SMAD4 (6.8 %), BRAF (6.5 %), and NRAS (3.9 %). Compared with the wild type, TP53 mutations were associated with low microsatellite instability/microsatellite stability (MSI-L/MSS) (P = 0.007), tumor location (P = 0.043), and histological grade (P = 0.0009); KRAS mutations were associated with female gender (P = 0.026), distant metastasis (P = 0.023), TNM stage (P = 0.013), and histological grade (P = 0.004); APC mutations were associated with patients <64 years of age at diagnosis (P = 0.04); PIK3CA mutations were associated with tumor location (P = 4.97e-06) and female gender (P = 0.018); SMAD4 mutations were associated with tumor location (P = 0.033); BRAF mutations were associated with high MSI (MSI-H; P = 6.968e-07), tumor location (P = 1.58e-06), and histological grade (P = 0.04). Mutations in 164 individuals were found to be pathogenic or likely pathogenic. A total of 26 patients harbored MSI-H tumors and they all had at least one detected gene mutation. Mutated genes were enriched in signaling pathways associated with CRC. The present findings have important implications for improving the personalized treatment of patients with CRC in China.

IL-8 from CD248-expressing cancer-associated fibroblasts generates cisplatin resistance in non-small cell lung cancer.

Chemotherapy-resistant non-small cell lung cancer (NSCLC) presents a substantial barrier to effective care. It is still unclear how cancer-associated fibroblasts (CAFs) contribute to NSCLC resistance to chemotherapy. Here, we found that CD248+ CAFs released IL-8 in NSCLC, which, in turn, enhanced the cisplatin (CDDP) IC50 in A549 and NCI-H460 while decreasing the apoptotic percentage of A549 and NCI-H460 in vitro. The CD248+ CAFs-based IL-8 secretion induced NSCLC chemoresistance by stimulating nuclear factor kappa B (NF-κB) and elevating ATP-binding cassette transporter B1 (ABCB1). We also revealed that the CD248+ CAFs-based IL-8 release enhanced cisplatin chemoresistance in NSCLC mouse models in vivo. Relative to wild-type control mice, the CD248 conditional knockout mice exhibited significant reduction of IL-8 secretion, which, in turn, enhanced the therapeutic efficacy of cisplatin in vivo. In summary, our study identified CD248 activates the NF-κB axis, which, consecutively induces the CAFs-based secretion of IL-8, which promotes NSCLC chemoresistance. This report highlights a potential new approach to enhancing the chemotherapeutic potential of NSCLC-treating cisplatin.

Impact of dipeptidyl peptidase-4 inhibitors on glucose-dependent insulinotropic polypeptide in type 2 diabetes mellitus: a systematic review and meta-analysis.

Aims: Glucose-dependent insulinotropic polypeptide (GIP) confers a variety of metabolic benefits in type 2 diabetes mellitus (T2DM). This meta-analysis was conducted to investigate the impact of dipeptidyl peptidase 4 (DPP4) inhibitors on GIP levels in T2DM patients. Methods: Medline (PubMed), CENTER (Cochrane Library), and Embase (Ovid) were searched and randomized controlled trials (RCTs) evaluating the impact of DPP4 inhibitors on fasting and postprandial GIP levels were obtained. For postprandial GIP, only studies with the data of GIP changes reported as the total area under the curve (AUCGIP) using a meal or oral glucose tolerance test were included. A random-effects model was used for data pooling after incorporating heterogeneity. Results: Overall, 14 RCTs with 541 T2DM patients were included. Compared to placebo/no treatment, the use of DPP4 inhibitors significantly increased the fasting GIP level (standard mean difference [SMD]: 0.77, 95% confidence interval [CI]: 0.48-1.05, P<0.001; I2 = 52%) and postprandial AUCGIP (SMD: 1.33, 95% CI: 1.02-1.64, P<0.001; I2 = 65%). Influence analysis by excluding one dataset at a time showed consistent results. Sensitivity analyses only including studies with radioimmunoassay showed also consistent results (fasting GIP: SMD: 0.75, 95% CI: 0.51-1.00, P<0.001; I2 = 0%; and postprandial AUCGIP: SMD: 1.48, 95% CI: 1.18-1.78, P<0.001; I2 = 54%). Further subgroup analyses demonstrated that the influence of DPP4 inhibitors on fasting and postprandial GIP levels in T2DM patients was not significantly changed by study characteristics such as study design, patient mean age, baseline glycated hemoglobin (HbA1c) concentration, body mass index (BMI), background treatment, treatment duration, or method for postprandial GIP measurement (all P for subgroup effects <0.05). Conclusion: The use of DPP4 inhibitors effectively increases the fasting and postprandial GIP concentrations in T2DM patients. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022356716.

Efficacy and Safety of Ertugliflozin Added to Metformin: A Pooled Population from Asia with Type 2 Diabetes and Overweight or Obesity.

INTRODUCTION: The efficacy and safety of ertugliflozin have not been well characterized in Asian populations with type 2 diabetes (T2D) and overweight or obesity as defined by the Chinese Diabetes Society [body mass index (BMI) ≥ 24 kg/m2]. METHODS: These post hoc analyses of pooled data from two randomized, double-blind, 26-week studies assessed the efficacy and safety of ertugliflozin (5 mg or 15 mg) compared with placebo in participants from Asia with T2D and baseline BMI ≥ 24 kg/m2, with inadequate glycemic control on metformin. Longitudinal analyses were used to calculate least squares (LS) mean [95% confidence interval (CI)] change from baseline in glycemic indices and body weight. The proportions of participants achieving efficacy targets and experiencing adverse events (AEs) were assessed. RESULTS: The 445 participants had a mean age of 55.5 years, T2D duration 6.6 years, glycated hemoglobin (HbA1c) 8.1%, and BMI 27.6 kg/m2. At week 26, placebo-adjusted LS mean (95% CI) changes from baseline for ertugliflozin 5 mg and 15 mg, respectively, were - 0.78% (- 0.95% to - 0.61%) and - 0.80% (- 0.98% to - 0.63%) for HbA1c, and - 1.74 kg (- 2.29 kg to - 1.19 kg) and - 2.04 kg (- 2.60 kg to - 1.48 kg) for body weight. A greater proportion of participants receiving ertugliflozin 5 mg and 15 mg versus placebo, respectively, achieved HbA1c < 7.0% (42.1% and 46.3% vs. 13.9%), body weight reduction ≥ 5% (35.5% and 38.3% vs. 11.1%), and systolic blood pressure < 130 mmHg (42.4% and 34.5% vs. 21.7%). The proportion of participants with AEs was 52.6% (ertugliflozin 5 mg), 52.3% (ertugliflozin 15 mg), and 55.6% (placebo). CONCLUSIONS: In participants from Asia with T2D inadequately controlled by metformin monotherapy, and BMI ≥24 kg/m2, ertugliflozin (5 mg or 15 mg) resulted in greater glycemic and body weight reductions compared with placebo and was generally well tolerated. TRIAL REGISTRATION: Clinicaltrials.gov identifiers NCT02033889, NCT02630706.

Effect of dipeptidyl peptidase-4 inhibitors on postprandial glucagon level in patients with type 2 diabetes mellitus: A systemic review and meta-analysis.

Aims: Hyperglucagonemia occurs in the pathogenesis of type 2 diabetes mellitus (T2DM). In this meta-analysis, we summarized the effects of DPP4 inhibitors on glucagon levels in patients with T2DM. Materials and methods: Randomized controlled trials (RCTs) comparing the influence of DPP4 inhibitors on circulating glucagon levels with placebo or other oral antidiabetic drugs (OADs) in patients with T2DM were identified by searches of Medline (PubMed), Embase (Ovid), and CENTER (Cochrane Library). Only studies reporting changes in glucagon level presented as total area under the curve (AUCglucagon) using a meal or oral glucose tolerance test were included. Results were combined using a random-effects model that incorporated potential heterogeneity among the included studies. Results: A total of 36 RCTs with moderate to high quality were included. Overall, the numbers of T2DM patients included for the meta-analyses comparing DPP4 inhibitors with placebo and other OADs were 4266 and 1652, respectively. Compared to placebo, DPP4 inhibitors significantly reduced circulating glucagon levels (standard mean difference [SMD]: -0.32, 95% CI: -0.40 to -0.24, P<0.001; I2 = 28%). Analysis of subgroups revealed that study characteristics had no significant effect on results, such as study design (parallel group or crossover), number of patients, mean patient age, proportion of men, baseline HbA1c, duration of diabetes, background therapy, treatment duration, or methods for glucagon measurement (all P for subgroup differences >0.05). Moreover, DPP4 inhibitors significantly reduced glucagon levels compared to other OADs (SMD: -0.35, 95% CI: -0.53 to -0.16, P<0.001; I2 = 66%), and the reduction in glucagon was greater in comparison with insulin secretagogues than in comparison with non-insulin secretagogues (P for subgroup difference =0.03). Systematic review registration: https://inplasy.com/, identifier INPLASY202280104. Conclusions: DPP4 inhibitors are effective at reducing the circulating postprandial glucagon level in T2DM patients.

Influence of dipeptidyl peptidase-4 inhibitors on glycemic variability in patients with type 2 diabetes: A meta-analysis of randomized controlled trials.

Objective: The influence of dipeptidyl peptidase-4 (DPP4) inhibitors on glycemic variability compared to other oral antidiabetic drugs (OADs), measured based on the mean amplitude of glycemic excursions (MAGE), has not been comprehensively analyzed. The aim of the study was to perform a meta-analysis to compare the effects of DPP4 inhibitors on MAGE with other OADs in type 2 diabetes mellitus (T2DM) patients without concurrent insulin treatments. Methods: The Medline (PubMed), Embase (Ovid), and CENTER (Cochrane Library) databases were searched for relevant randomized controlled trials (RCTs). Study characteristics and outcome data were independently extracted by two authors. A random-effect model was used to combine the results. Results: Fourteen studies with 855 patients were included. Compared to other OADs, DPP4 inhibitors significantly reduced MAGE (mean difference [MD]: -0.69 mmol/L, 95% confidence interval [CI]: -0.95 to -0.43, P<0.001) with mild heterogeneity (I2 = 28%). Predefined subgroup analyses suggested that DPP4 inhibitors were more effective in reducing MAGE compared to insulin secretagogues (MD: -0.92 mmol/L, P<0.001) and non-secretagogues (MD: -0.43 mmol/L, P=0.02), as well as compared to sulfonylureas (MD: -0.91 mmol/L, P<0.001) and sodium glucose cotransporter 2 inhibitors (MD: -0.67 mmol/L, P=0.03). Conclusions: DPP4 inhibitors may significantly reduce glycemic variability compared to other oral anti-diabetic drugs, as evidenced by MAGE in T2DM patients with no concurrent insulin treatment. Systematic review registration: INPLASY, registration number: INPLASY2021120113.

State-level political partisanship strongly correlates with health outcomes for US children.

The Cook Partisan Voting Index (PVI) determines how strongly a state leans toward the Democratic or Republican Party in US presidential elections compared to the nation. We set out to determine the correlation between childhood health outcomes and state-level partisanship using PVI. Sixteen measures of childhood health were obtained from several US governmental agencies for 2003-2017. The median PVI for every state was calculated for the same time period. Pearson's rho determined the correlation between PVI and each health outcome. Multiple regression was also conducted, adjusting for educational attainment and percentage of non-White residents. We also compared childhood health in moderately Democratic and Republican states (5-9.9% more Democratic/Republican than the national mean) and, similarly, for extremely Democratic and Republican states (10% or more Democratic/Republican than the national mean), using Wilcoxon tests. For all 16 health measures, the median values in Democratic-leaning states represented better outcomes than Republican-leaning states (9/16 had a beta value for linear regression associated with P < 0.05). When compared to Republican states, the median values in moderately Democratic states represented better outcomes for 14 of 16 health measures (9/14 associated with P < 0.05). Similarly, the median values for extremely Democratic states represented better outcomes with regard to all 16 health measures, when compared to Republican-leaning states (8/16 associated with P < 0.05).Conclusions: Democratic-leaning states displayed superior outcomes for multiple childhood health measures when compared to Republican counterpart states. Future research should investigate the significance of these findings and attempt to determine which state-level policies may have contributed to such disparate health outcomes. What is Known: • In the United States, many health disparities exist among children along racial, economic and geographic lines. • Many US states lean strongly towards either the Democratic or Republican political parties in federal elections. What is New: • Trends for multiple measures of childhood health vary in association with the political partisanship of the state being examined. • Multiple barometers of childhood health are superior in Democratic-leaning states, while no measures are better in Republican-leaning states.

Enhanced Temporal Coupling between Thalamus and Dorsolateral Prefrontal Cortex Mediates Chronic Low Back Pain and Depression.

Numerous neuroimaging studies have demonstrated that the brain plasticity is associated with chronic low back pain (cLBP). However, there is a lack of knowledge regarding the underlying mechanisms of thalamic pathways for chronic pain and psychological effects in cLBP caused by lumbar disc herniation (LDH). Combining psychophysics and magnetic resonance imaging (MRI), we investigated the structural and functional brain plasticity in 36 patients with LDH compared with 38 age- and gender-matched healthy controls. We found that (1) LDH patients had increased psychophysical disturbs (i.e., depression and anxiety), and depression (Beck-Depression Inventory, BDI) was found to be an outstanding significant factor to predict chronic pain (short form of the McGill Pain Questionnaire, SF-MPQ); (2) the LDH group showed significantly smaller fractional anisotropy values in the region of posterior corona radiate while gray matter volumes were comparable in both groups; (3) resting state functional connectivity analysis revealed that LDH patients exhibited increased temporal coupling between the thalamus and dorsolateral prefrontal cortex (DLPFC), which further mediate the relationship from chronic pain to depression. Our results emphasized that thalamic pathways underlying prefrontal cortex might play a key role in regulating chronic pain and depression of the pathophysiology of LDH.

Factors associated with switching from sulphonylureas to dipeptidyl peptidase 4 inhibitors among patients with type 2 diabetes in the United States.

AIMS: Studies examining the prevalence of and factors associated with switching from sulphonylureas (SUs) to dipeptidyl peptidase 4 (DPP-4) inhibitors in real-world settings are lacking. We assessed the factors associated with switching from SUs to DPP-4 inhibitors in the United States. MATERIALS AND METHODS: This retrospective cohort study was conducted using the Optum Clinformatics® Data Mart (2009-2018). Adults with type 2 diabetes and newly prescribed at least two SUs were included and were followed for 2 years after the initiation of SU (index date). We compared the characteristics of those who switched from SUs to DPP-4 inhibitors (only; no additional antidiabetic drugs) with those who continued with SUs (without adding other antidiabetic drugs) using multivariate logistic regression. Multinomial regression analyses were also conducted to assess the factors associated with switching to different drug classes versus continuation with SUs. RESULTS: In a sample of 119 107 new SU users, 2.2% (2633) switched to DPP-4 inhibitors, 3.8% (4542) switched to antidiabetic drugs other than DPP-4 inhibitors, 68.3% (81 394) discontinued SUs but did not switch to another antidiabetic drug, 12.9% (15 345) continued with SUs and added other antidiabetic drugs, and 12.8% (15 193) continued with SUs only. Multivariate logistic regression showed that those who had significantly higher likelihood of switching were younger, female [vs. males; adjusted odds ratio (AOR) = 0.70], and living in the south; had previous use of DPP-4 inhibitors (AOR = 1.71); were not using antidiabetic drugs at baseline; had more baseline diabetes-related emergency room visits (AOR = 1.13), depression (AOR = 1.34), post-index hypoglycaemia (AOR = 2.20), and an earlier index year; and were glyburide users (vs. glimepiride users; AOR = 1.29). CONCLUSIONS: The discontinuation rate for SUs is high. Factors associated with switching from SUs to DPP-4 inhibitors included age, sex, geographic region, baseline antidiabetic drug use, type of SU, baseline diabetes-related emergency room visits, hypoglycaemia and depression.

Is periodontal disease a risk indicator for colorectal cancer? A systematic review and meta-analysis.

AIMS: Existing epidemiological studies have suggested that periodontal disease (PD) may be a risk indicator for colorectal cancer (CRC). However, no formal systematic review and meta-analysis have been performed. Therefore, we aimed to evaluate the association between PD and CRC risk in this study. MATERIALS AND METHODS: We used the PubMed, EMBASE, Cochrane Library and Web of Science to search for related articles published from 1 January 1966 to 16 July 2020. Stata (Version 15) software was used to calculate the total risk ratio (RR) and 95% confidence interval (CI) of the included studies through the random-effects model to assess the association between PD and CRC risk. RESULTS: Nine studies were included in the narrative synthesis, and seven studies were included in the meta-analysis. Results showed that PD significantly increased the risk of CRC by 44% (RR, 1.44; 95% CI, 1.18-1.76; I2 , 55.2%). CONCLUSION: We found an association between PD and CRC. PD can be a potential risk indicator for the occurrence and development of CRC, and further studies are needed to assess causality. Hence, effective periodontal treatment could be a valuable preventive measure for CRC.

Effect of Dipeptidyl Peptidase 4 Inhibitors Used in Combination with Insulin Treatment in Patients with Type 2 Diabetes: A Systematic Review and Meta-analysis.

INTRODUCTION: To evaluate the efficacy and safety of dipeptidyl peptidase 4 inhibitors (DPP4i) used in combination with insulin in patients with type 2 diabetes mellitus (T2DM). METHODS: We searched the MEDLINE, Embase, and Cochrane library databases for randomized controlled trials (RCTs) published through June 2018. Studies with at least a 12-week treatment period were included to compare the addition of DPP4i to insulin with insulin control therapy. Meanwhile, groups on a stable insulin dosage (insulin-stable subgroup) or titrating insulin dosage (insulin-flexible subgroup) were analyzed separately. RESULTS: Twenty-one RCTs with 3697 patients randomized to a DPP4i/insulin treatment arm and 3538 to an insulin control arm were included. DPP4i, when added to insulin therapy, led to a significantly greater reduction in HbA1c (- 0.57%, 95% CI - 0.66, - 0.48) and provided significantly greater odds of achieving the HbA1c target < 7% (OR 3.45; 95% CI 2.58, 4.63). These effects were achieved in the context of a decrease in the daily insulin requirement, without increases in hypoglycemia risk and body weight, compared with the control treatment. Subgroup analysis showed control-adjusted reductions in HbA1c from baseline in the insulin-stable subgroup (-  0.64%; 95% CI - 0.74, - 0.53) and the insulin-flexible subgroup (- 0.43%; 95% CI - 0.56, - 0.30). Other results occurred similarly in both subgroups. CONCLUSIONS: The addition of DPP4i to insulin is associated with a statistically significant reduction in glycemic control as measured by HbA1c, fasting plasma glucose, and 2-h postprandial glucose, without increasing the risk of hypoglycemia and weight gain. These conclusions were also observed in both stable-dose and flexible-dose insulin subgroups.

Nanoporous V-Doped Ni5P4 Microsphere: A Highly Efficient Electrocatalyst for Hydrogen Evolution Reaction at All pH.

Hydrogen economy is one of the most promising candidates to replace the current energy system on depleting fossil fuels. As a clean and sustainable way to produce hydrogen, electrocatalytic water splitting attracts ever-increasing interest from the research community. Although the wide application of platinum group metal (PGM) catalysts is limited because of the scarcity and high cost toward hydrogen evolution reaction (HER), the non-PGM electrocatalysts usually suffer from unsatisfactory activity and poor durability. In this work, we report an active and durable V-doped Ni5P4 electrocatalyst that can be used for all-pH HER. Particularly, V-Ni5P4 has an HER activity that is comparable to that of Pt in preferred alkaline media, with overpotentials as low as 13 mV and 295 mV at current densities of 10 and 1000 mA cm-2, respectively. The low-cost V-Ni5P4 that enables ultrahigh current density (i.e., at the level of A cm-2) would be of great interest to the hydrogen production industry.

Efficacy and safety of metformin and sitagliptin-based dual and triple therapy in elderly Chinese patients with type 2 diabetes: Subgroup analysis of STRATEGY study.

AIMS/INTRODUCTION: To assess the efficacy and safety of metformin/sitagliptin-based dual/triple therapy in elderly Chinese patients with type 2 diabetes mellitus. MATERIALS AND METHODS: This subgroup analysis included individuals aged ≥65 years from the STRATEGY study, a two-stage study in which type 2 diabetes mellitus patients with unsatisfactory glycemic control on metformin were first treated with the dual combination of metformin and sitagliptin for 16 weeks (n = 681), and then, if glycemic control had not been achieved, were treated with a third add-on oral antihyperglycemic drug for another 24 weeks (n = 291). The efficacy end-point was change in glycated hemoglobin (HbA1c) in each stage, and the safety end-point was adverse events with a focus on hypoglycemia. RESULTS: At week 16, the change in HbA1c was -0.81% from baseline, and the percentages of patients who achieved HbA1c targets of <7% and <7.5% were 44.9 and 67.2%, respectively. After 24 weeks, a further average HbA1c reduction of -0.60% was observed with specific reductions of -0.70% with glimepiride, -0.63% with gliclazide, -0.51% with repaglinide and -0.45% with acarbose. The proportions of patients who achieved HbA1c targets of <7% and <7.5% were 65.4 and 81.3%, respectively, over the entire study. The rates of drug-related adverse events and hypoglycemia were, respectively, 4.1 and 4.3% in the dual therapy stage, and 5.2% and 7.1% in the triple therapy stage, without occurrence of severe hypoglycemia. CONCLUSIONS: In elderly Chinese type 2 diabetes mellitus patients, metformin/sitagliptin-based dual and triple oral therapy can provide clinically meaningful glycemic control and is generally well tolerated with a low incidence of hypoglycemia.

Hierarchical Mesoporous MXene-NiCoP Electrocatalyst for Water-Splitting.

The utilization of nonprecious metal electrocatalysts for water-splitting may be the ultimate solution for sustainable and clean hydrogen energy. MXene, an emerging two-dimensional material, exhibits many unique properties such as possible metal-like conductivity, hydrophilic surface, and rich chemistry, rendering a group of promising catalysts and catalyst support materials. In this study, exfoliated Ti3C2 MXenes serve as a substrate to perpendicularly grow uniform mesoporous NiCoP nanosheets through an in situ interface-growth strategy and subsequent phosphorization. The obtained Ti3C2@mNiCoP materials with a stable hierarchical sandwich structure possess excellent conductivity, large surface area, and uniform mesopores with high pore volume. With these beneficial properties, the Ti3C2@mNiCoP material exhibits superior overall water-splitting performance compared with that of its building-block counterparts, matching the state-of-the-art water-splitting electrocatalysts.

Promoting Formation of Oxygen Vacancies in Two-Dimensional Cobalt-Doped Ceria Nanosheets for Efficient Hydrogen Evolution.

As an alternative for depleting fossil fuel energy, hydrogen economy desires low-cost and efficient hydrogen production from water splitting. In order to explore a cheap, abundant, active, and durable catalyst for the electrocatalytic hydrogen evolution reaction (HER), two-dimensional (2D) ceria nanosheets are produced through a thermal decomposition exfoliation method from CeCO3OH with a layer-stacked structure. The additional cobalt dopant promotes formation of oxygen vacancies in ceria nanosheets and, in turn, optimizes hydrogen binding/water dissociation and increases the active sites. As a result, the 2D Co-doped CeO2 nanosheets exhibit an excellent catalytic performance in alkaline HER such that the overpotential is as low as 132 and 215 mV to deliver a high current density of 100 and 500 mA cm-2, respectively, outperforming Pt. Such 2D Co-doped CeO2 nanosheets are also durable HER electrocatalysts, as the activity loss during an extended period of operation is nearly negligible.

Efficacy and safety of sitagliptin added to treatment of patients with type 2 diabetes inadequately controlled with premixed insulin.

To improve understanding of the safety and efficacy of adding sitagliptin to treatment of patients with type 2 diabetes taking premixed insulin, data from patients using premixed insulin ± metformin (screening HbA1c ≥7.5% and ≤11%) in either of two clinical trials in which sitagliptin 100 mg once-daily or placebo was added to various formulations of insulin treatment, were analysed. In both trials, insulin doses were to remain stable throughout the 24-week trial period. At week 24, the between-group difference (sitagliptin - placebo) in the least squares mean (95% confidence intervals) change from baseline in HbA1c in patients using premixed insulin was -0.43% (-0.58, -0.28), P <0.001. Adverse events were generally similar between the treatment groups. The incidence of symptomatic hypoglycaemia was slightly higher with sitagliptin, and the incidence of hypoglycaemia requiring medical attention was slightly higher with placebo; in both cases the difference was not statistically significant. The data from this pooled analysis confirm the utility of sitagliptin used in combination with premixed insulin in patients with type 2 diabetes.

Roles of genetic and microenvironmental factors in cancer epithelial-to-mesenchymal transition and therapeutic implication.

Epithelial-to-mesenchymal transition (EMT) is a process in which epithelial cells lose their cell-cell contacts resulting in the formation of mesenchymal cells with migratory properties. Increasing evidence indicate EMT plays a key role in the invasion, metastasis and therapeutic resistance of cancer and maintenance of the phenotype of cancer stem cells (CSCs), which makes the prognosis of patients worse. The progression of cancer from epithelial tissue towards a malignant phenotype is driven by multiple factors that remodel the tissue architecture. This review summarizes and analyzes current studies of genetic and microenvironmental factors in inducing and maintaining cancer EMT and therapeutic implications. This will enable a better understanding of the contribution of EMT-associated factors to cancer progression and highlights that genetic factors and tumor microenvironment responsible for EMT could be used as attractive targets for therapeutic intervention.

Direct head-to-head comparison of glycaemic durability of dipeptidyl peptidase-4 inhibitors and sulphonylureas in patients with type 2 diabetes mellitus: A meta-analysis of long-term randomized controlled trials.

We performed a meta-analysis of randomized controlled trials (RCTs) to compare the long-term glycaemic durability of dipeptidyl-peptidase 4 (DPP-4) inhibitors vs that of sulphonylureas (SUs) in patients with type 2 diabetes mellitus (T2DM), in terms of the changes in glycated haemoglobin (HbA1c) levels from an intermediate time point (26 or 52 weeks) to 104 weeks of treatment. The Medline (PubMed), Embase (Ovid), and CENTER (Cochrane Library) databases were searched for relevant RCTs. Eight RCTs were included. Compared with SUs, DPP-4 inhibitors were associated with significantly smaller increases in the HbA1c level from 24 to 28 weeks to 104 weeks (mean difference [MD]: -0.16%, 95% confidence interval [CI]: -0.21 to -0.11; P < .001) and from 52 weeks to 104 weeks (MD -0.06%, 95% CI -0.10 to -0.02; P = .001). No significant heterogeneities were detected among the included comparisons (I2 = 0%). These results suggest that long-term treatment with DPP-4 inhibitors confers better durability of glycaemic response than treatment with SUs in patients with T2DM, which may indicate that DPP-4 inhibitors better preserve islet ß-cell function compared with SUs.

Prevalence, treatment patterns and control rates of metabolic syndrome in a Chinese diabetic population: China Cardiometabolic Registries 3B study.

AIMS/INTRODUCTION: To investigate the prevalence and risk factors of metabolic syndrome (MetS) in Chinese type 2 diabetes mellitus patients, and assess the effect of MetS on the treatment patterns and blood glucose, blood pressure and blood lipids goal achievements. MATERIALS AND METHODS: Data from 25,454 type 2 diabetes mellitus patients including demographic data, anthropometric measurements, treatment patterns, and blood glucose and lipid profiles were retrospectively analyzed. RESULTS: Using modified Adult Treatment Panel III MetS criteria, the prevalence of MetS was 57.4% in type 2 diabetes mellitus patients. Multivariable logistic regression analysis showed that type 2 diabetes mellitus patients, who also fulfilled the criteria for MetS, tended to be women, living in the northeast, with a diabetes duration ≥5 years and leading a sedentary lifestyle. Most MetS (53.4%) and non-MetS (57%) diabetes patients received oral hypoglycemic drugs. Insulin or insulin combination therapies were more applied in MetS (37.5%) than in non-MetS (33.1%) diabetes patients, and the percentages of MetS diabetes patients receiving antihypertensive and lipid-modulating drugs were 52.9% and 28.2% vs 38.3% and 19.3% of the non-MetS diabetes patients. Just 37.5%, 15.6% and 32.9% of the MetS diabetes patients vs 54.6%, 45.6% and 40.4% of the non-MetS diabetes patients achieved the individual target goals for control of blood glucose (glycosylated hemoglobin <7%), blood pressure (systolic blood pressure <130 mmHg, diastolic blood pressure <80 mmHg) and blood lipids (total cholesterol <4.5 mmol/L), whereas just 2.1% achieved all three target goals. CONCLUSIONS: MetS with a high prevalence in Chinese type 2 diabetes mellitus patients is associated with poor blood glucose, blood pressure and blood lipids control rate.

A long noncoding RNA positively regulates CD56 in human natural killer cells.

Natural killer (NK) cells are innate immune lymphocytes that play critical roles in host defense against viral infection and surveillance against malignant transformation. Long noncoding RNAs (lncRNAs) are important immune system regulators. Here, we analyzed human primary lymphocyte lncRNA expression profiles to identify NK-lncRNA signatures. We detected numerous novel NK-specific lncRNAs with potential roles in regulating human NK cell differentiation and function. Expression of lnc-CD56, an NK-specific lncRNA, was positively correlated with that of CD56, a classical human NK cell surface marker. We showed that lnc-CD56 may function as a positive regulator of CD56 in primary human NK cells and differentiated NK cells from human CD34+ hematopoietic progenitor cells. Our data provide an annotated human NK cell lncRNA expression catalog and demonstrate a key role for lncRNAs in NK cell biology.