Efficacy and safety of janagliflozin monotherapy in Chinese patients with type 2 diabetes mellitus inadequately controlled on diet and exercise: A multicentre, randomized, double-blind, placebo-controlled, Phase 3 trial.

AIMS: To evaluate the efficacy and safety of janagliflozin, a selective renal sodium-glucose cotransporter-2 inhibitor, as monotherapy in drug-naive Chinese patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: This Phase 3 trial included a 24-week, multicentre, randomized, double-blind, placebo-controlled period, followed by a 28-week extension period. A total of 432 patients with glycated haemoglobin (HbA1c) levels ≥7.0% (53 mmol/mol) and ≤10.5% (91 mmol/mol) were randomized (1:1:1) to receive once-daily placebo, 25 mg or 50 mg janagliflozin. After 24 weeks, patients on placebo were switched and re-randomized (1:1) to 25 mg or 50 mg janagliflozin, whereas patients on janagliflozin maintained the initial therapy. The primary endpoint was change from baseline in HbA1c after 24 weeks. RESULTS: At Week 24, the placebo-adjusted least squares mean changes in HbA1c were -0.80% (95% confidence interval [CI] -0.98% to -0.62%)/-8.7 mmol/mol (95% CI -10.7 mmol/mol to -6.8 mmol/mol) and -0.88% (95% CI -1.06% to -0.70%)/-9.6 mmol/mol (95% CI -11.6 mmol/mol to -7.7 mmol/mol), respectively (P < 0.001 for both). A higher proportion of patients achieved HbA1c <7.0% (53 mmol/mol) with janagliflozin 25 mg and janagliflozin 50 mg compared with placebo (47.2%, 49.3%, and 23.5%, respectively). Both janagliflozin doses significantly decreased fasting plasma glucose, 2-hour postprandial glucose, body weight and systolic blood pressure, as well as increased high-density lipoprotein (HDL) cholesterol and insulin sensitivity compared with placebo (P < 0.05 for all). The trends in improvement of these variables were sustained during the 28-week extension period. Overall incidences of adverse events were 67.8%, 71.5% and 60.7% with janagliflozin 25 mg, janagliflozin 50 mg and placebo, respectively. The incidence of urinary tract infections and genital fungal infections was low. No severe hypoglycaemia or ketoacidosis occurred. CONCLUSIONS: Janagliflozin 25 mg and 50 mg monotherapy once-daily effectively improved glycaemic control, reduced body weight and blood pressure, improved HDL cholesterol and insulin sensitivity, and was generally well tolerated.

Evaluating the Efficacy of Atorvastatin on Patients with Carotid Plaque by an Innovative Ultrasonography.

BACKGROUND: The present study aimed to explore the efficacy of atorvastatin on patients with carotid plaque, applying superb microvascular imaging (SMI), and contrast-enhanced ultrasound (CEUS) for evaluating carotid intraplaque neovascularization. METHODS: A total of 82 patients (82 carotid plaques) who were randomized into treatment group and control group underwent conventional ultrasound, CEUS, and SMI examinations. Patients in treatment group received a dose of 20 mg atorvastatin per day for 6 months while those in control group received placebo instead. Lipid parameters were assessed and intraplaque neovascularization were evaluated by CEUS and SMI before and 6 months after atorvastatin treatment. RESULTS: No significant differences were found between the 2 groups at the study entry. Patients with atorvastatin treatment received marked improvement in total cholesterol, triglyceride, and LDL-cholesterol compared with those in control group (P < .001). In treatment group, SMI-detected intraplaque neovascularization reduced from 69.23% to 48.72% while CEUS-detected ones reduced from 76.92% to 69.23%. By contrast, the percentage of intraplaque neovascularization in control group did not change too much either by SMI (65.12%, 67.44%) or CEUS (74.41%, 74.41%). The consistency between CEUS and SMI was above .75 at all assessments (P < .001). CONCLUSIONS: Atorvastatin treatment works for patients with carotid plaque by reducing LDL-cholesterol and improving plaque regression. Second, the consistency between SMI and CEUS in visualizing intraplaque neovascularization is good. That indicates a high possibility to identify carotid plaque instability by a safer and cheaper ultrasonography without contrast agent.

The prevalence and characteristics of obstructive sleep apnea in hospitalized patients with type 2 diabetes in China.

Data on the prevalence of obstructive sleep apnea in subjects with type 2 diabetes mellitus in China is scarce. We conducted a multi-centre, cross-sectional study involving 12 hospitals from six regional cities to investigate the prevalence of obstructive sleep apnea in hospitalized patients with type 2 diabetes mellitus and to explore the association between obstructive sleep apnea and related risk factors, diabetic complications and comorbidities in China. Each hospital recruited at least 70 consecutive patients with type 2 diabetes mellitus who were admitted to the endocrinology ward. A total of 880 participants were enrolled and administered overnight sleep monitoring with a portable monitor (ApneaLink™, ResMed, San Diego, CA, USA); other information was collected from medical charts and a standardized questionnaire. In this study, 60.0% (95% confidence interval: 56.8%, 63.2%) of hospitalized patients in China with type 2 diabetes mellitus had comorbid obstructive sleep apnea (apnea-hypopnea index ≥ 5). Only 1.5% (eight of 528) of the patients with both conditions had been diagnosed previously with obstructive sleep apnea. The prevalence of moderate-severe (apnea-hypopnea index ≥ 15) and severe obstructive sleep apnea (apnea-hypopnea index ≥ 30) was estimated to be 25.6% (22.7, 28.5%) and 10.3% (8.3, 12.4%), respectively. Age, sex, body mass index, snoring, reported breath-holding in sleep or gasping or choking arousal, sleepiness, diabetes duration, hypertension, diabetic nephropathy and cardiovascular diseases history were correlated significantly with the severity of obstructive sleep apnea. In China, the prevalence of obstructive sleep apnea in hospitalized patients with type 2 diabetes mellitus is high. Routine screening for and treatment of obstructive sleep apnea is an important, but often neglected, part of the management of diabetes.

Bilateral cerebellar epithelioid hemangioblastoma with possible ependymal differentiation in a patient with von Hippel-Lindau disease.

There are controversies regarding the histogenesis of stromal cells of hemangioblastoma, and no hypothesis has conclusively been proven. We report a case of unusual hemangioblastoma in a middle-aged man with von Hippel-Lindau disease. Neuroimaging revealed multifocal gadolinium-enhancing masses were located within both sides of the cerebellar hemisphere. Histologically, only small areas showing the typical morphology of hemangioblastoma were recognized in masses. Most areas of masses were composed of cohesive epithelioid tumor cells with abundant cytoplasm and distinct boundaries. Epithelioid tumor cells were arranged around blood vessels, exhibiting perivascular anuclear zone structures like ependymoma. The epithelioid tumor cells were diffusely positive for vimentin, CD99, neuron-specific enolase, GFAP and focally positive for epithelial membrane antigen (EMA) and D2-40 in a dot-like pattern. Variable-sized lipid droplets and glycogen particles were noted in the cytoplasm of epithelioid tumor cells under an electron microscope. A diagnosis of epithelioid cellular hemangioblastoma with possible ependymal differentiation (WHO grade I) was made. To our knowledge, only a few cases of hemangioblastoma show epithelioid appearance or EMA immunoreactivity. The present case indicates that the stromal cells of hemangioblastoma might originate from primitive neuroectodermal cells, and they have the capacity to show a distinctive sign of glial or ependymal differentiation.

[The effects of Nrf2 gene expression induced by RU486 at different doses on A549 cell damage induced by paraquat].

OBJECTIVE: To observe the effects of Nrf2 gene expression induced by RU486 at different doses on A549 cell damage induced by paraquat (PQ). METHODS: After A549 cells transfected with Ad-RUNrf2 were treated by RU486 at the doses of 10(-10), 10(-9), 10(-8) and 10(-7) mol/L for 6 h, A549 cell cultures were exposed to 10(-3) mol/L of PQ for 48 h. Then qRT-PCR and EMSA assays were used to detect the expression of Nrf2 gene, and qRT-PCR and ELISA assays were utilized to measure the effects of Nrf2 gene on the expression of the inflammatory cytokines IL-6, IL-10 and TNF-α, apoptotic factors Caspase-3, Caspase-9 and Cytochrome C. The oxidation factors (CAT and MDA protein contents) were observed by Chemical Colorimetric Analysis. RESULTS: Nrf2 gene relative expression and protein contents increased with RU486 concentrations, and the above expression was the highest when the concentration of RU486 was 10(-7) mol/L, which was significantly higher than those in control and PQ exposure groups (P < 0.01 or P < 0.05). The relative gene expression and protein expression of IL-6 and TNF-α enhanced with the reduced concentrations of RU486, which were the lowest when RU486 concentration was 10(-7) mol/L, as compared with control and PQ exposure groups (P < 0.01 or P < 0.05), while the change of IL-10 content was the opposite. The relative expression of Caspase3, Caspase9 and Cytochrome C genes also increased with the reduced concentrations of RU486, which were the lowest when RU486 concentration was 10(-7) mol/L, as compared with control and PQ exposure groups (P < 0.01 or P < 0.05). The content of CAT enhanced with RU486 concentration, which was the highest when RU486 concentration was 10(-7) mol/L, as compared with control and PQ exposure groups (P < 0.05). But the change of MDA content was the contrary. CONCLUSION: Nrf2 expression induced by RU486 can promote the balance of oxidation-antioxidation system in A549 cells and inhibit the inflammation and apoptosis factors, which has a protective effect on A549 cell injury induced by PQ.

[Effect of ulinastatin on oxidative stress and nuclear factor E2-related factor 2 expression in the lung tissues of acute hydrogen sulfide intoxicated rats].

OBJECTIVE: To investigate the dynamic changes of oxidative stress and nuclear factor-E2 related factor 2 (Nrf2) expression in the lung tissues of acute hydrogen sulfide (H2S) intoxicated rats and intervention effects of ulinastatin (UTI). METHODS: A total of 96 SD rats of clean grade were divided randomly into four groups: normal control group (n = 8), UTI control group (n = 8), H2S -intoxicated model group (n = 40), and UTI treatment group (n = 40). The H2S-intoxicated model group and UTI treatment group were exposed to H2S (283.515 mg/m3) by inhalation for 1h, then UTI treatment group was intraperitoneally exposed to UTI at the dose of 10(5) U/kg for 2 h. H2S-intoxicated model group and UTI treatment group were sacrificed at 2, 6, 12, 24 and 48 h after exposure, respectively. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione (GSH) in the rat lung tissues were measured. The expression levels of Nrf2 mRNA in the rat lung tissues were detected. Pathological changes of rat lung tissues were observed under a light microscope and the lung injury scores were evaluated. RESULTS: Compared with control group, the pulmonary SOD, CAT and GSH levels at 2,6 and 12 h after exposure and the pulmonary GSH-Px levels at 2, 6, 12 and 24 h after exposure in H2S-intoxicated model group significantly decreased (P < 0.05 or P < 0.01). The levels of pulmonary MDA at 2, 6, 12 and 24 h after exposure in H2S-intoxicated model group were significantly higher than those in normal control group (P < 0.01). As compared with H2S -intoxicated model group, the pulmonary GSH-Px activities at 6 and 12 h after exposure, the pulmonary CAT activities at 2, 6 and 12 h after exposure, the pulmonary GSH levels at 2, 6, 12 and 24 h after exposure and the pulmonary SOD activities at 2, 6, 12, 24 and 48 h after exposure in UTI treatment group significantly increased (P < 0.05 or P < 0.01), the pulmonary MDA levels at 2, 6 and 12 h after exposure in UTI treatment group significantly decreased (P < 0.01). The expression levels of Nrf2 mRNA at 2, 6, 12, 24 h after exposure in H2S-intoxicated model group were 0.314 +/- 0.011, 0.269 +/- 0.010, 0.246 +/- 0.011 and 0.221 +/- 0.018, respectively, which were significantly higher than those (0.149 +/- 0.012) in control group (P < 0.01). As compared with H2S-intoxicated model group, the expression levels (0.383 +/- 0.017, 0.377 +/- 0.014, 0.425 +/- 0.017, 0.407 +/- 0.011 and 0.381 +/- 0.010) of Nrf2 mRNA at 2, 6, 12, 24 and 48 h after exposure in UTI treatment group significantly increased (P < 0.01). The lung injury at 24 h after exposure in H2S-intoxicated model group was higher than that in UTI treatment group. Histopathological examination showed that the scores of lung injury at 12, 24 and 48 h after exposure in UTI treatment group was significantly lower than those in H2S-intoxicated model group (P < 0.01). CONCLUSION: Oxidative stress and Nrf2 activation may be the important factors in rat lung injury induced by H2S-intoxicated, UTI may reduce the rat lung injury and protect the rat lung from damage induced by H2S by inhibiting ROS, improving the imbalance in redox and up-regulating Nrf2 mRNA expression.

High iodine promotes autoimmune thyroid disease by activating hexokinase 3 and inducing polarization of macrophages towards M1.

Autoimmune thyroid disease (AITD), the most common autoimmune disease, includes Graves' disease (GD) and Hashimoto's thyroiditis (HT). Currently, the pathogenesis of AITD is not fully understood. Our study aimed to examine the presence of macrophage polarization imbalance in AITD patients, to investigate whether high iodine can cause macrophage polarization imbalance, and to investigate the role of key genes of metabolic reprogramming in macrophage polarization imbalance caused by high iodine. We synergistically used various research strategies such as systems biology, clinical studies, cell culture and mouse disease models. Gene set enrichment analysis (GSEA) revealed that M1 macrophage hyperpolarization was involved in the pathogenesis of AITD. In vitro and in vivo experiments showed that high iodine can affect the polarization of M1 or M2 macrophages and their related cytokines. Robust rank aggregation (RRA) method revealed that hexokinase 3 (HK3) was the most aberrantly expressed metabolic gene in autoimmune diseases. In vitro and in vivo studies revealed HK3 could mediate macrophage polarization induced by high iodine. In summary, hyperpolarization of M1-type macrophages is closely related to the pathogenesis of AITD. High iodine can increase HK3 expression in macrophages and promote macrophage polarization towards M1. Targeting HK3 can inhibit M1 polarization induced by high iodine.

Candidate sex-associated gene identification in Trachinotus ovatus (Carangidae) using an integrated SLAF-seq and bulked segregant analysis approach.

It is difficult to distinguish the sexes of Trachinotus ovatus based on appearance, and little data about sex-determining genes are available for this species. Here, we generated 200 F2 individuals using the parents R404 and R403. DNA samples were collected from 50 individuals of each sex and aggregated into sex-specific DNA pools. Specific-locus amplified fragment sequencing was integrated with bulked segregant analysis to detect candidate sex-associated genes. Approximately 3,153,153 high-quality single-nucleotide polymorphism (SNP) markers and 135,363 high-quality insertion-deletion (Indel) markers were generated. Six candidate regions within chromosome 14, encompassing 132 candidate genes, were identified as closely related to sex. Based on annotations, six genes (EVM0019817, EVM0004192, EVM0001445, EVM0005260, EVM0014734, and EVM0009626) were predicted to be closely associated with sex. These results present an efficient genetic mapping approach that lays a foundation for molecular sex discrimination in T. ovatus.

Dorzagliatin add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 3 trial.

Metformin, the first-line therapy for type 2 diabetes (T2D), decreases hepatic glucose production and reduces fasting plasma glucose levels. Dorzagliatin, a dual-acting orally bioavailable glucokinase activator targeting both the pancreas and liver glucokinase, decreases postprandial glucose in patients with T2D. In this randomized, double-blind, placebo-controlled phase 3 trial, the efficacy and safety of dorzagliatin as an add-on therapy to metformin were assessed in patients with T2D who had inadequate glycemic control using metformin alone. Eligible patients with T2D (n = 767) were randomly assigned to receive dorzagliatin or placebo (1:1 ratio) as an add-on to metformin (1,500 mg per day) for 24 weeks of double-blind treatment, followed by 28 weeks of open-label treatment with dorzagliatin for all patients. The primary efficacy endpoint was the change in glycated hemoglobin (HbA1c) levels from baseline to week 24, and safety was assessed throughout the trial. At week 24, the least-squares mean change from baseline in HbA1c (95% confidence interval (CI)) was -1.02% (-1.11, -0.93) in the dorzagliatin group and -0.36% (-0.45, -0.26) in the placebo group (estimated treatment difference, -0.66%; 95% CI: -0.79, -0.53; P < 0.0001). The incidence of adverse events was similar between groups. There were no severe hypoglycemia events or drug-related serious adverse events in the dorzagliatin and metformin combined therapy group. In patients with T2D who experienced inadequate glycemic control with metformin alone, dorzagliatin resulted in effective glycemic control with good tolerability and safety profile ( NCT03141073 ).

MicroRNA-199-3p targets Sp1 transcription factor to regulate proliferation and epithelial to mesenchymal transition of human lung cancer cells.

The present study was undertaken to study the function of miRNA-199-3p in the regulation of human lung cancer growth and metastasis. The results showed significant (P < 0.05) downregulation of miRNA-199-3p in lung cancer tissues and cell lines. Overexpression of miR-197 caused considerable inhibition of the viability and colony formation of the lung cancer cells. The inhibition of proliferation was found to be due to the arrest of the SK-LU-1 lung cancer cells. At the G2/M phase of the cell cycle. In silico analysis and subsequent the dual-luciferase assays showed that miR-199-3p targets Sp1 at molecular. The expression of Sp1 was significantly (P < 0.05) upregulated in lung cancer cells and tissues. Nonetheless, miR-199-3p overexpression could cause post-transcriptional suppression of Sp1. Silencing of Sp1suppress the proliferation of SK-LU-1 lung cancer cells. However, overexpression Sp1 transcription factor prevents the tumor-suppressive effects of miR-199-3p on lung cancer cells. Additionally, miR-199-3p was found to suppresses the migration, invasion and epithelial-to-mesenchymal transition of human lung cancer cells. Summing up, miRNA-199-3p/SP1 axis controls the growth and metastasis of SK-LU-1 lung cancer cells.

Application and Effectiveness of Big Data and Artificial Intelligence in the Construction of Nursing Sensitivity Quality Indicators.

In order to explore the quality management efficiency of applying big data and artificial intelligence in nursing quality index, a method of building a nursing management platform integrating nursing indicators and nursing events is proposed. Based on the investigation of the application demand of nursing information system, the method achieves timely data sharing and transmission through WLAN technology and realizes nursing management monitoring, nursing quality index enquiry, and automatic statistical analysis under the vertical management mode of nursing. The results showed that 77 people (73%) thought the time decreased, 19 people (18%) thought the time was the same, and 9 people (7%) thought the time increased. In terms of intelligent application and big data of nursing information management system, there is a significant difference in nursing management efficiency before and after using nursing management information system (P < 0.001). The nursing management control platform is designed and applied, and the nursing quality control method and actual management process are improved, which is very good for strengthening nursing quality management. The overall optimization of the quality control process is realized, which helps to mobilize the initiative and enthusiasm of nursing staff and continuously improve the effectiveness of nursing management and nursing efficiency.

Clinical retrospective study on the expression of the PD-L1 molecule in sporadic colorectal cancer and its correlation with K-ras gene mutations in Chinese patients.

OBJECTIVE: To detect the expression of PD-L1 and K-ras gene status in colorectal cancer tissues and analyze the relationship between PD-L1 expression and the clinicopathological features and K-ras gene status in colorectal cancer. METHODS: Two hundred fifty colorectal cancer tissues were collected from the First Affiliated Hospital of Nanchang University. The normal intestinal mucosal tissues of 20 patients were randomly selected for inclusion in the control group. PD-L1 expression was detected by immunohistochemistry. K-ras gene mutation in colorectal cancer tissues was detected by sequencing. The clinical significance of PD-L1 expression and relationship between PD-L1 expression and K-ras gene mutation were analyzed. RESULTS: The immunohistochemistry assay showed that PD-L1 was highly expressed in colorectal cancer. The positive expression of PD-L1 was increased with lymph node metastasis and high TNM stage. The 5-year survival rate of PD-L1-positive patients was significantly lower than that of PD-L1-negative patients. The K-ras gene mutation rate was 35.6%, and the main mutation site was in codon 12. The positive PD-L1 expression rate in patients with K-ras gene mutations was significantly higher than that in patients with wild-type K-ras gene mutations. CONCLUSION: PD-L1 is highly expressed in colorectal cancer, and its expression is related to metastasis and tumor stage. PD-L1 expression is closely related to K-ras gene mutation, and the K-ras gene status may affect PD-L1 expression. TRIAL REGISTRATION: retrospectively registered.

Challenges in diagnosis of spinal epidural abscess: A case report.

RATIONALE: Spinal epidural abscess (SEA) is a rare condition that shows a high prevalence in immunocompromised patients. The clinical presentation of SEA includes the "classic triad" of pain, fever, and neurological dysfunction. However, these nonspecific features can lead to a high rate of misdiagnosis. SEA may lead to paralysis or even death; thus, prognosis of these patients remains unfavorable. PATIENT CONCERNS: We report a case of a multilevel (T6-T12) SEA in a 22-year-old woman. DIAGNOSIS: The patient was initially diagnosed with spinal tuberculosis at a local hospital based on a history of tuberculosis exposure, as well as radiography and computed tomography. Histopathological examination of the tissue resected during laminectomy confirmed the diagnosis of SEA in this patient. INTERVENTIONS: The patient underwent multilevel laminectomy combined with long-term antibiotic therapy. OUTCOMES: Physical examination performed 16 months postoperatively revealed that superficial and deep sensation was restored to normal levels in the lower extremities with improvement in the patient's motor function (muscle strength 2/5). LESSONS: This case report indicates that whole spine magnetic resonance imaging is warranted in patients with SEA and that prompt surgical intervention is important at symptom onset. Long-term antibiotic therapy is also essential postoperatively.

Ulcerative colitis followed by the development of typical intestinal Behçet disease: A case report.

RATIONALE: Intestinal Behçet disease (intestinal BD) and inflammatory bowel disease (IBD) share a lot of characteristics, including genetic background, clinical manifestations, and therapeutic strategies, especially the extraintestinal manifestations, such as oral ulcers, arthralgia, eye lesions, skin lesions, etc, but the coexistence of these 2 diseases are uncommon. Behçet disease with gastrointestinal involvement in ulcerative colitis (UC) patient has been reported in just 1 previous case report, but, which can not be diagnosed as definite intestinal BD based on Korean novel diagnositic criteria due to lacking the typical ileocecal ulcer. PATIENT CONCERNS: We present a 23-year-old woman with ulcerative disease who developed typical intestinal BD, which is the first case report of patient with coexisting UC and typical intestinal BD. DIAGNOSES: This patient was diagnosed as coexistence of intestinal BD and UC base on the clinical manifestations, extra intestinal manifestations and typical colonoscopic findings. INTERVENTIONS: Steroid and methotrexate were administered. OUTCOMES: This patient achieved clinical remission and mucosal healing. LESSONS: Coexistence of intestinal BD and UC is uncommon, and the combination with steroid, methotrexate, and 5-aminosalicylic acids is an effective therapy.

Plasma soluble CD36, carotid intima-media thickness and cognitive function in patients with type 2 diabetes.

INTRODUCTION: Diabetes and atherosclerosis are both risk factors of cognitive deficits. Scavenger receptor CD36 is associated with increasing risk of diabetes and atherosclerosis, and may play a role in cognitive deficits. The aim of this study is to determine the correlations of plasma soluble CD36 concentrations with carotid intima-media thickness (IMT) and cognitive function in patients with type 2 diabetes. MATERIAL AND METHODS: We determined the levels of soluble CD36 (sCD36), blood lipids, fasting blood glucose, glycosylated hemoglobin, carotid atherosclerosis as IMT, cognitive function by the Montreal Cognitive Assessment (MoCA) scoring system, and other clinical characteristics in 357 patients with type 2 diabetes. RESULTS: Diabetic patients with the lowest quartile of IMT (Q1) had lower sCD36 concentrations (ANOVA, ptrend < 0.05) and higher MoCA scores than upper ones (Q2-Q4) (ptrend < 0.05), and those with the highest quartile of sCD36(Q4) had higher FBG, LDL-C and carotid IMT than lower ones (Q1-Q3) (ptrend < 0.05 for all). Plasma log10(sCD36) was significantly correlated with carotid IMT (r = 0.202, p < 0.001) after adjustment for age, gender, and education level. Carotid IMT was significantly associated with MoCA scores (r = 0.284, p < 0.001) after adjustment for, age, gender, education level, duration of DM and hypertension. There were no correlations between sCD36 and MoCA scores (r = -0.038, p = 0.470). CONCLUSIONS: Our study shows that sCD36 is associated with carotid IMT, and carotid IMT is inversely correlated with cognitive function in type 2 diabetic patients. Nevertheless, no cross-sectional association between sCD36 and MoCA scores was detected in this study.

HtrA1 Down-regulation Induces Cisplatin Resistance in Colon Cancer by Increasing XIAP and Activating PI3K/Akt Pathway.

The high temperature requirement factor A1 (HtrA1), a member of serine protease family, has been reported to be down-regulated in various cancer types and correlate with chemoresistance. However, the function of HtrA1 in colon cancer remains unclear. This study investigated the role of HtrA1 in cisplatin (CDDP) resistance of colon cancer. We found that HtrA1 was up-regulated in colon cancer cell line SW480 incubated with CDDP. By treating SW480 cells to a continuous exposure to CDDP, we developed CDDP-resistant SW480/CDDP cells and found that the mRNA and protein levels of HtrA1 were reduced. Besides, the stable knock-down of HtrA1 in SW480 transfected with HtrA1 shRNA could also induce chemoresistance against CDDP. To the contrary, ectopic expression of HtrA1 in SW480/CDDP cells abrogated CDDP resistance. The mechanism underlying HtrA-1 down-regulation induced chemoresisance was also investigated. In SW480/CDDP cells and SW480 cells with HtrA1 knock-down, X-linked inhibitor of apoptosis protein (XIAP) was increased, while the interfering of XIAP impeded CDDP resistance in SW480/CDDP cells. We also found that Akt was activated in SW480/CDDP cells and SW480 cells with HtrA1 knock-down. The inhibition of Akt activation reversed CDDP resistance. In conclusion, our results indicate that HtrA1 down-regulation induces CDDP resistance in colon cancer by increasing XIAP and activating PI3K/Akt pathway. This study provides evidence that HtrA1 might be a therapeutic target for overcoming CDDP resistance in colon cancer.

Effects of body mass index or dosage on gastrointestinal disorders associated with extended-release metformin in type 2 diabetes: Sub-analysis of a Phase IV open-label trial in Chinese patients.

AIM: To determine whether gastrointestinal (GI) tolerability of metformin monotherapy varies according to baseline BMI or at doses >1500mg/day in patients newly diagnosed with type 2 diabetes. METHODS: We performed a sub-analysis of the safety population from a prospective, multicenter, Phase IV open-label study in which 371 Chinese patients with type 2 diabetes received extended-release metformin monotherapy for 16 weeks. The incidence, severity and duration of GI adverse events (AEs) were compared between normal-weight (BMI<25kg/m(2), n=155) and overweight/obese (BMI≥25kg/m(2), n=216) patients. The primary objective was to determine whether baseline BMI affect the incidence, severity and duration of GI AEs, using Fisher's exact test and Student's t-test. Secondary objectives were to compare these factors according to final metformin dose (≤1500mg/day versus 2000mg/day). RESULTS: The proportion of patients who reported ≥1 GI AE did not differ significantly between BMI groups (25.2% of the normal-weight group versus 21.3% of the overweight/obese group; p=0.3840). Patients who reported GI AEs in the two BMI groups experienced similar GI AE severity (p=0.5410), mean duration (p=0.3572) and duration distribution (p=0.1347). There was no significant difference in GI AE severity and duration between metformin dosage groups (≤1500mg/day versus 2000mg/day). CONCLUSIONS: Newly-diagnosed Chinese type 2 diabetes patients of normal weight are no more likely than overweight/obese patients to suffer from increased incidence rates, severity or duration of GI AEs when treated with first-line extended-release metformin monotherapy. Doses of 2000mg/day did not increase the severity or duration of GI AEs.

Correlations between serum levels of 25-hydroxyvitamin D and carotid atherosclerosis in patients with type 2 diabetes in Shanghai.

OBJECTIVE: To explore the potential association between the serum levels of 25-hydroxyvitamin D [25(OH)D] and carotid atherosclerosis in patients with type 2 diabetes. MATERIAL AND METHODS: Three hundred and fifty patients with type 2 diabetes were enrolled in this study in Shanghai, China. B-mode ultrasound was used to detect carotid plaques as indicators of atherosclerosis and measure carotid artery intima-media wall thickness (C-IMT) at two sites of carotid artery. Subjects were divided into group A (patients with carotid plaques) and group B (patients without carotid plaques) and be assessed clinically. Serum levels of 25(OH)D and other clinical parameters were measured. Multivariate logistic regression was performed to find predictors of carotid atherosclerosis in the entire group. RESULTS: The levels of serum 25(OH)D were lower in group A than in group B[19.60 (13.30-25.73) vs 23.19 (18.10-30.06)ng/ml, P<0.001]. The C-IMT levels [(1.00±0.17 vs 0.88±0.20)mm, Ptrend<0.001] and proportion of people with carotid plaques(44/88 vs 20/87, Ptrend<0.001) in the lowest quartile of 25(OH)D were higher than in the highest quartile. Vitamin D concentrations were inversely associated with HbA1c in women(r=-0.194, P=0.006), and C-IMT in men(r=-0.409, P<0.001). Logistic regression analysis showed age, male sex, current smoke, history of hypertension, SBP, LDL-C and lg[25(OH)D] (OR: 0.924, 95%CI: 0.893-0.955, P<0.001) were independently associated with the presence of carotid plaques in T2DM. CONCLUSIONS: Serum vitamin D level is significantly and independently associated with carotid atherosclerosis in patients with T2DM in Shanghai, China.

Serum levels of 25-hydroxyvitamin D are associated with cognitive impairment in type 2 diabetic adults.

Hypovitaminosis D is highly prevalent in type 2 diabetes. The aim of this study is to determine the serum levels of 25-hydroxyvitamin D [25(OH)D] in type 2 diabetic patients with and without mild cognitive impairment (MCI), and examine the relationship of 25(OH)D and MCI with other clinical factors. One hundred and sixty-five diabetic patients were enrolled in this study. Among whom, 95 patients were considered as MCI [Montreal Cognitive Assessment score (MoCA) < 26] and the other 70 as no MCI (MoCA ≥ 26). Subjects were assessed clinically. Diabetic patients with MCI had a longer duration of DM, fewer years of education, elevated fasting blood glucose (FBG), resistant index (RI) of carotid, and lower levels of 25(OH)D {[17.35 (13.02-25.92) vs 28.00 (19.67-34.30)] ng/ml, P < 0.001}. The MoCA score was positively correlated with log10[25(OH)D], education year, and inversely correlated with duration of DM, history of hypertension, intima-media thickness (IMT), FBG, max-RI, and min-RI. Log10[25(OH)D] was positively correlated with MoCA score, and inversely correlated with IMT, in multivariate regression analysis adjusted for age, sex, and education year, 25(OH)D (ß = 0.210, P = 0.003), history of hypertension (ß = -0.191, P = 0.007), IMT (ß = -0.194, P = 0.007), and FBG (ß = -0.157, P = 0.026) independently predicted MoCA score. In conclusion, our results suggest that levels of serum 25(OH)D are inversely associated with the cognitive impairment in diabetic patients. Vitamin D may be a potential protective factor for cognitive impairment in patients with type 2 diabetes.

Risk factors of mild cognitive impairment in middle aged patients with type 2 diabetes: a cross-section study.

UNLABELLED: The aim of this study was to evaluate the risk factors of mild cognitive impairment (MCI) in middle-aged patients with type 2 diabetes (T2DM). METHODS: Montreal Cognitive Assessment (MoCA) was applied as cognition assessment implement. One hundred and fifty-seven middle-aged type 2 diabetic patients were enrolled in this cross-section study (age 40~69, mean age 55 ± 7). There were 93 patients with MCI (MoCA score<26) in MCI group and 64 with normal cognitive function (MoCA score ≥ 26) in control group. Information of history of disease, family history, data of BMI, WHR, HbA1c, FINS, C-Peptide (C-P), SBP, DBP, blood lipid (TG, TC, LDL-C, HDL-C and carotid ultrasound (carotid IMT, carotid resistance index [RI]) was collected. RESULTS: There were significant differences in the rate of patients with hypertension ([40.63 vs. 58.06%], P=0.026), duration of diabetes mellitus ([3.09 ± 4.04 y vs. 4.80 ± 4.94 y], P=0.024), C-P ([2.79 ± 1.09 ng/ml vs. 2.26 ± 1.00 ng/ml], P=0.008), Max C-IMT ([0.81 ± 0.15 mm vs. 0.91 ± 0.15 mm], P<0.001), Min C-RI (0.71 ± 0.06 vs. 0.68 ± 0.06, P<0.05), and no significant differences in the duration of hypertension and hyperlipidemia, BMI, WHR, HbA1c, SBP, DBP and blood lipid between control group and MCI group. MoCA scores were positively correlated with C-P (r=0.252, P=0.005), and negatively correlated with the history of hypertension (r=-0.244, P=0.002), duration of DM (r=-0.161, P=0.044), Max C-IMT (r=-0.253, P=0.005) and Min C-RI (r=-0.183, P=0.023). Multiple regression analysis showed that history of hypertension (Beta=-0.267, P=0.002), C-P (Beta=0.281, P=0.001) and Min C-RI (Beta=-0.221, P=0.011) were significantly independent determinants for the MoCA scores. CONCLUSIONS: The longer duration of diabetes, history of hypertension, lower serum C-P levels, thickened C-IMT and higher C-RI could be risk factors of MCI in type 2 diabetic patients. This finding could have an important impact on the management of cognitive decline in diabetic patients.