Multiparameter spectral CT-based radiomics in predicting the expression of programmed death ligand 1 in non-small-cell lung cancer.

AIM: To explore the value of radiomics for predicting the expression of programmed death ligand 1 (PD-L1) in non-small-cell lung cancer (NSCLC) based on multiparameter spectral computed tomography (CT) images. MATERIALS AND METHODS: A total of 220 patients with NSCLC were enrolled retrospectively and divided into the training (n=176) and testing (n=44) cohorts. The radiomics features were extracted from the conventional CT images, mono-energy 40 keV images, iodine density (ID) maps, Z-effective maps, and electron density maps. The logistic regression (LR) and support vector machine (SVM) algorithms were employed to build models based on radiomics signatures. The prediction abilities were qualified by the area under the curve (AUC) obtained from the receiver operating characteristic (ROC) curve. Internal validation was performed on the independent testing dataset. RESULTS: The combined model for PD-L1 ≥1%, which consisted of the radiomics score (rad-score; p<0.0001), white blood cell (WBC; p=0.027) counts, and air bronchogram (p=0.003), reached the highest performance with the AUCs of 0.873 and 0.917 in the training and testing dataset, respectively, which was better than the radiomics model with the AUCs of 0.842 and 0.886. The combined model for PD-L1 ≥50%, which consisted of rad-score (p<0.0001) and WBC counts (p=0.027), achieved the highest performance in the training and testing dataset with AUCs of 0.932 and 0.903, respectively, which was better than the radiomics model with AUCs of 0.920 and 0.892, respectively. CONCLUSION: The radiomics model based on the multiparameter images of spectral CT can predict the expression level of PD-L1 in NSCLC. The combined model can obtain higher prediction efficiency and serves as a promising method for immunotherapy selection.

Predicting coronary artery disease by carotid color doppler ultrasonography.

OBJECTIVE: In this study, the color ultrasound indicators of carotid atherosclerosis (CAS) intima-media thickness (IMT) and atherosclerotic plaque (AP) were retrospectively analyzed for the prediction of CHD with the help of compressed speckle denoising. PATIENTS AND METHODS: A total of 248 patients with suspected coronary atherosclerosis admitted to the Department of Cardiovascular Medicine of The First Affiliated Hospital of Harbin Medical University from August 2020 to January 2022 were retrospectively recruited as research subjects. RESULTS: The plaque detection rate (71.83%), IMT (1.26 ± 0.75) mm, and plaque index (PI) (2.31 ± 0.95) in the Obs group were greatly higher. The IMT and PI values in the patients with two CALs were superior to those in patients with a single CAL, and the IMT and PI values in the patients with three CALs were higher than those in patients with two CALs, illustrating considerable differences between the two groups (p < 0.05). The predictive sensitivity of IMT combined with AP was higher than that of IMT and AP (p < 0.05), and the predictive specificity of AP results was markedly inferior to that of IMT and IMT combined with AP (p < 0.05). CONCLUSIONS: The ultrasound examination of CAS had obvious predictive value for the occurrence and disease severity of CHD. The higher the IMT and AP, the higher the incidence and severity of CAD.

Effects of Birinapant on Proliferation and Invasion of MGC-803 Gastric Cancer Cells and Mechanism Underlying These Effects.

We studied the effects of birinapant, a mimetic of the second mitochondria-derived activator of caspase (SMAC), on invasion and proliferation of MGC-803 gastric cancer cells and the molecular mechanisms underlying these processes. The expression of cellular inhibitor of apoptosis 1 (cIAP1) and TNF receptor-associated factor 3 (TRAF3) in gastric cancer cell line MGC-803 and normal gastric mucosa GES-1 cells were analyzed by Western blotting and cell immunofluorescence assay. After pretreatment of MGC-803 cells with birinapant, a Transwell invasion assay was used to evaluate the cell invasion ability. MGC-803 cells were implanted under the skin of BALB/c nude mice. The tumors were removed 10 days later and its size was measured. Protein expression of proliferating cell nuclear antigen (PCNA) in the subcutaneous tumors was analyzed by immunohistochemical method. In addition, the expression of cIAP1, TRAF3, pNF-κB, and NF-κB in control and birinapant-treated cells was compared by Western blotting and the rate of cell apoptosis was evaluated by flow cytometry. In untreated MGC-803 gastric cancer cells, the expression of cIAP1 was higher and the expression of TRAF3 was lower than in normal gastric mucosa cell line GES-1. Pretreatment with birinapant inhibited the invasion and proliferation of MGC-803 cells and promoted cell apoptosis. Birinapant also promoted the expression of TRAF3 and inhibited the expression of cIAP1 and pNF-κB in MGC-803 cells. Thus, birinapant inhibited the expression of cIAP1, prevented degradation of TRAF3, and suppressed invasion and proliferation of MGC-803 cells by promoting cell apoptosis.

[Prevalence and associated risk factors of pre-hypertension and hypertension in young and middle-aged population in Nanjing].

Objective: To investigate the prevalence and associated risk factors of pre-hypertension and hypertension in young and middle-aged population in Nanjing. Methods: Subjects of the study were those who underwent physical examination in the physical examination center of Nanjing Drum Tower Hospital from 2009 to 2016. The prevalence and risk factors of pre-hypertension and hypertension in young (aged 18-44 years old) and middle-aged people (aged 45-59 years old) were analyzed. Results: A total of 142 857 participants aged 18-59 years old were analyzed. Among them, 64 220 cases in the pre-hypertension group and 13 912 cases in the hypertension group. The prevalence of hypertension was 9.74% (12.51% in males and 5.82% in females). The prevalence of pre-hypertension was 44.95% (53.31% in males and 33.15% in females). In the middle-aged group, the prevalence of pre-hypertension and hypertension were 51.68% and 15.13%, respectively, which was higher than that in the young group (37.95% and 4.13%, respectively). The prevalence of pre-hypertension and hypertension in 2013-2016 was 45.37% and 10.65%, respectively, which was higher than that in 2009-2012(44.52% and 8.78%). In addition, the prevalence of abnormal blood glucose metabolism, abnormal blood lipid metabolism and abnormal glucose and lipid metabolism in the pre-hypertension group was higher than that in the normal blood pressure group, but lower than that in the hypertension group (P<0.001). A logistic regression analysis indicated that age, overweight or obesity, hyperglycemia, hypertriglyceridemia and hypercholesterolemia were risk factors of pre-hypertension in male. Age, overweight or obesity, hyperglycemia, hypertriglyceridemia, hypercholesterolemia and hyper-low density cholesterolemia were associated with hypertension in male and with pre-hypertension and hypertension in female. Conclusions: Middle age, overweight/obesity, elevated fasting plasma glucose, elevated triglyceride and elevated total cholesterol were risk factors of pre-hypertension and hypertension in both men and women. Intervention on the related risk factors should be conducted as early as possible.

UV response characteristics of mixed-phase MgZnO thin films with different structure distributions, high Iuv/Idark ratios, and fast speed MgZnO UV detectors with tunneling breakdown mechanisms.

High-performance ultraviolet (UV) detectors with both high responses and fast speeds are hard to make on homogeneous crystal semiconductor materials. Here, the UV response characteristics of mixed-phase MgZnO thin films with different internal structure distributions are studied. The mixed-phase MgZnO-based detector with the given crystal composition has a high response at both deep UV light (96 A W-1 at 240 nm) and near UV light (80 A W-1 at 335 nm). Meanwhile, because of the quasi-tunneling breakdown mechanism within the device, the high-response UV detector also shows a fast response speed (tr = 0.11 µs) and recovery speed (td1 = 26 µs) at deep UV light, which is much faster than both low-response mixed-phase MgZnO-based UV detectors with other structure constitutions and reported high-response UV devices on homogenous crystal materials. The Idark of the device is just 4.27 pA under a 5 V bias voltage, so the signal-to-noise ratio of the device reached 23852 at 5.5 uW cm-2 235 nm UV light. The new quasi-tunneling breakdown mechanism is observed in some mixed-phase MgZnO thin films that contain both c-MgZnO and h-MgZnO parts, which introduce a high response, signal-to-noise ratio, and fast speed into mixed-phase MgZnO-based UV detectors at weak deep UV light.

[Efficacy and safety of Changsulin® compared with Lantus® in type 2 diabetes: a phase â ¢ multicenter, randomized, open-label, parallel, controlled clinical trial].

Objective: To compare the efficacy and safety of Changsulin® with Lantus® in treating patients with type 2 diabetes mellitus (T2DM). Methods: This was a phase Ⅲ, multicenter, randomized, open-label, parallel-group, active-controlled clinical trial. A total of 578 participants with T2DM inadequately controlled on oral hypoglycemic agents were randomized 3∶1 to Changsulin® or Lantus® treatment for 24 weeks. The efficacy measures included changes in glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), 2h postprandial plasma glucose (2hPG), 8-point self-monitoring of blood glucose (SMBG) profiles from baseline, and proportions of subjects achieving targets of HbA1c and FPG. The safety outcomes included rates of hypoglycemia, adverse events (AEs) and anti-insulin glargine antibody. Results: After 24 weeks of treatment, mean HbAlc decreased 1.16% and 1.25%, FPG decreased 3.05 mmol/L and 2.90 mmol/L, 2hPG decreased 2.49 mmol/L and 2.38 mmol/L in Changsulin® and in Lantus®, respectively. No significant differences could be viewed in above parameters between the two groups (all P>0.05). There were also no significant differences between Changsulin® and Lantus® in 8-point SMBG profiles from baseline and proportions of subjects achieving the targets of HbA1c and FPG (all P>0.05). The rates of total hypoglycemia (38.00% and 39.01% for Changsulin® and Lantus®, respectively) and nocturnal hypoglycemia (17.25% and 16.31% for Changsulin® and Lantus®, respectively) were similar between the two groups (all P>0.05). Most of the hypoglycemia events were asymptomatic, and no severe hypoglycemia were found in both groups. No differences were observed in rates of AEs (61.77% vs.52.48%) and anti-insulin glargine antibody (after 24 weeks of treatment, 6.91% vs.3.65%) between the two groups (all P>0.05). Conclusions: Changsulin® shows similar efficacy and safety profiles compared with Lantus® and Changsulin® treatment was well tolerated in patients with T2DM.

[The value of serum dehydroepiandrosterone sulfate in differential diagnosis of Cushing's syndrome].

Objective: To evaluate the changes and diagnostic value of serum dehydroepiandrosterone sulfate (DHEAS) in Cushing's syndrome (CS) with different etiologies. Methods: The study retrospectively recruited patients diagnosed as CS in Drum Tower Hospital affiliated to Nanjing University Medical School between January 2012 and June 2019, including 36 patients (8 males, 28 females, with an average age of 44 years) with Cushing disease (CD) and 64 patients (6 males, 58 females, with an average age of 39 years) with adrenal CS (ACS). Meanwhile, 97 patients diagnosed as nonfunctional adrenal adenoma (NFA) were also included as controls. Clinical characteristics, laboratory data, adrenocorticotropic hormone (ACTH), serum DHEAS level and sex-and age-adjusted DHEAS ratio of the three groups were collected. The sensitivity and specificity of DHEAS and its ratio in differential etiology diagnosis of CS were compared using receiver operating characteristic (ROC) curve analysis. Results: Compared to NFA group, ACS patients had lower DHEAS levels [0.39 (0.39, 0.63) µmol/L vs 2.96 (1.92, 4.60) µmol/L, P<0.01] and lower DHEAS ratio [0.58 (0.27, 0.98) vs 3.95 (3.08, 6.83), P<0.01]. DHEAS [6.49 (4.32, 11.63) µmol/L] and DHEAS ratio [9.17 (4.49, 15.41)] in CD patients were significantly higher compared to those in NFA and ACS patients (all P<0.01). There were 53 ACS patients (82.8%) with suppressed ACTH level (<2.2 pmol/L) and 11 patients (17.2%) with normal/high ACTH level (≥2.2 pmol/L). The level of 24 hour urine free cortisol in normal/high ACTH level group was lower than the suppressed ACTH group [(1 299±511) nmol/24 h vs (1 972±876) nmol/24 h, P=0.04]. No significant differences were found in the DHEAS and DHEAS ratio between the two groups. ROC analysis showed that the area under the curve of serum DHEAS and DHEAS ratio in diagnosing ACS from CD was 0.997 and 0.990, respectively. The optimal cut-off values for DHEAS and its ratio were 2.06 µmol/L and 2.10, respectively. The diagnostic sensitivity and specificity of DHEAS were 97.5% and 100%, and those of DHEAS ratio were 95.0% and 100%, respectively. Conclusion: There are significant differences in serum DHEAS level and DHEAS ratio between ACS and CD patients, which might be used as indicators for the identification of the two main CS etiologies, especially in the identification of ACS patients without plasma ACTH suppression from CD patients.

[Clinical features and outcomes of surgical versus conservative management in patients with subclinical Cushing's syndrome].

Objective: To examine the clinical characteristics and metabolic features of subclinical Cushing's syndrome (SCS), and determine the effects of surgical or conservative approaches on the hormone levels and metabolic comorbidities in patients with SCS, thereby providing the evidence for decision-making in SCS management. Methods: A total of 56 consecutive SCS patients were selected in Drum Tower Hospital Affiliated to Nanjing University Medical School between 2010 and 2018, with 41 patients undergoing surgical treatment and 15 patients receiving conservative therapy. Meanwhile, 56 and 68 cases of sex-and age-matched patients diagnosed as nonfunctional adrenal adenoma (NFA) and adrenal Cushing's syndrome (CS) were included respectively. Clinical characteristics of patients in different groups were compared. Hormone levels and metabolic comorbidities were also observed during follow-up. Results: There were 56 SCS patients, including 15 males and 41 females, with an age of (52.0±12.6) years. The circadian rhythms of adrenocorticotropic hormone (ACTH) and cortisol disappeared in CS and SCS groups. Compared to NFA group, patients with SCS were characterized by suppressed plasma ACTH level [2.40 (1.11, 4.33) pmol/L vs 4.23 (2.74, 6.26) pmol/L], elevated midnight cortisol level [(240±121) nmol/L vs (59±8) nmol/L] and increased cortisol level after 1 mg overnight dexamethasone suppression test [(241±130) nmol/L vs (34±12) nmol/L] (all P<0.01). The derangement of ACTH-cortisol axis was more obvious in CS patients compared to SCS patients. The prevalence of hypertension, glucose intolerance, dyslipidemia and osteopenia/osteoporosis were higher in SCS patients compared to NFA patients (75.0% vs 41.1%, 33.9% vs 12.5%, 62.5% vs 28.6%, 35.7% vs 8.9%, all P<0.05). The 24-hour urine free cortisol correlated positively with systolic blood pressure, glycated hemoglobin A1c (HbA1c) and fasting blood glucose in SCS patients (r=0.335, 0.562 and 0.463, respectively, all P<0.05). In the surgical group, body weight, body mass index (BMI) and blood pressure decreased significantly after surgery (all P<0.05). Glucose intolerance/diabetes mellitus improved in 6 of 9 patients, BMI of 4 of 11 overweight/obesity patients normalized, and hypertension in 54.5% of patients (12/22) showed improvement after surgery. However, no alterations of hormone levels and metabolic parameters were observed in conservatively-managed patients. Conclusions: Patients with SCS are characterized by mild autonomous cortisol secretion and increased risk of metabolic comorbidities. Compared with conservative management, hormone abnormalities were corrected and metabolic abnormalities were improved in some SCS patients after surgery.

[Evaluation on the effect of clinic standardized blood pressure measurement model applying to first blood pressure measurement among community population aged 35 years old and above].

Objective: To evaluate the effect of clinic standardized blood pressure measurement model (SBPM) applying to first blood pressure measurement among community population aged 35 years old and above. Methods: SBPM was implemented in the community health service center of Dapuqiao street, Huangpu district of Shanghai from June 1, 2018, and the data between June 1 and December 31, 2018 was used as the SBPM data. The first-diagnosis blood pressure measurement data in this center between June 1 and December 31, 2017 was used as the conventional measurement (CM) model data. The detection rate of elevated blood pressure under SBPM was standardized according to the gender and age distribution of subjects in CM. The equilibrium of the value distribution of the end digit of blood pressure value in different pressure-measuring models and difference of elevated blood pressure rate of subjects with different characteristics and seasons were analyzed by using the χ(2) test, and the difference of standardized elevated blood pressure rate in different pressure-measuring models was analyzed by using the U test. Results: The SBPM included 1 548 subjects and 639 (41.28%) of them were males. The CM included 2 952 inpatients and 1 196 (40.51%) of them were males. The frequency of the end digit of blood pressure in SBPM ranged from 9.04% to 10.72%, and both systolic and diastolic blood pressure showed a balanced distribution of end digit (P values were 0.996 and 0.981 respectively). The frequency of blood pressure end digital in the CM ranged from 0.37% to 67.92%, and both systolic and diastolic blood pressure showed an unbalanced distribution (both P values <0.001). The crude rate and standardized elevated blood pressure rate in SBPM were 23.19% (359/1 548) and 23.05%, which were higher than that in CM, about 7.22% (213/2 952) (both P values <0.001). The elevated blood pressure rate in SBPM in summer, autumn and winter was 18.85% (141/748), 26.72% (152/591) and 31.58% (66/209), respectively, which was higher than that in CM, about 6.28% (91/1 450), 7.20% (82/1 139) and 11.02% (40/363), respectively (all P values <0.001). Conclusion: The quality of blood pressure data and the efficiency of hypertension screening of SBPM are better than those of CM when applying to first blood pressure measurement among community population aged 35 years old and above.

[Adrenal androgen measurement for assessing the selectivity of adrenal venous sampling in primary aldosteronism].

Objective: To investigate the usefulness of adrenal androgens for assessing the selectivity of adrenal venous sampling (AVS). Methods: Between January 2010 and December 2016, 37 consecutive patients [with an average age of (47±14) years, 16 males and 21 females] with primary aldosteronism (PA) who underwent AVS were enrolled. AVS procedures were performed with the bilateral simultaneous technique without cosyntropin stimulation. Cortisol, androstenedione, dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEAS) concentrations were measured in adrenal venous (AV) and peripheral venous (PV) samples, respectively. Results: The selectivity index (SI) based on androstenedione and DHEA was higher than that of cortisol (SI-left: 13.9, 13.1 vs 6.05, P=0.006, 0.035; SI-right: 30.4, 18.5 vs 11.6, P=0.028, 0.051). However, the SI based on DHEAS was lower than that of cortisol (SI-left: 1.3 vs 6.0, P=0.002; SI-right: 1.5 vs 11.6, P=0.038). Plasma androstenedione and DHEA concentrations were positively correlated with cortisol and aldosterone in AV samples (all P<0.001). Compared to cortisol, the variation ratio of AV androstenedione and DHEA was lower from t(-15) to t(0) (0.23, 0.43 vs 0.52, both P<0.05). Using the receiver operating characteristic curve, a SI ≥ 3.0 for androstenedione or DHEA provided optimal sensitivity(97.7%, 91.9%) and specificity (93.8%, 93.8%) in AVS. Conclusion: Given the greater AV/PV ratios and reduced variability compared to cortisol, the adrenal androgens androstenedione and DHEA are useful for assessing the selectivity of AVS without cosyntropin stimulation and may be superior analytes in conditions with marked variability of cortisol levels or with adrenocortical tumors co-secreting cortisol and aldosterone.

Analysis of the correlation between non-alcoholic fatty liver disease and bone metabolism indicators in healthy middle-aged men.

OBJECTIVE: To investigate the relationship between bone metabolic indicators and non-alcoholic fatty liver disease (NAFLD) in healthy middle-aged men. PATIENTS AND METHODS: The bone metabolic indicators of 232 healthy middle-age men with NAFLD (NAFLD group) and 308 healthy controls without fatty liver (Control group) were measured, including non-collagenous osteocalcin, the procollagen type 1 N-terminal propeptide (P1NP), beta-C-terminal telopeptide of type I collagen (ß-CTX). The Student's t-test was used to analyze the differences in the bone metabolic indicators, age, clinical data, biochemical indicators, and the indicators of glucose and lipid metabolism between the two groups. The correlation of fatty liver-related indicators was detected using the logistic regression analysis. RESULTS: The body mass index (BMI), diastolic blood pressure, and heart rate in NAFLD group were significantly higher than those in Control group. Among the indicators of glucose and lipid metabolism in NAFLD group, the levels of blood glucose [fasting plasma glucose, postprandial blood glucose and hemoglobin A1c (HbA1c)] were significantly higher than those in Control group. In addition, the insulin resistance and secretion indexes were also significantly higher than those in Control group. The levels of lipid metabolic indicators such as triglyceride were higher, but high-density lipoprotein cholesterol was lower than that in Control group. From logistic regression analysis, the BMI, Homeostasis model assessment (HOMA)-ß, HOMA-IR, HbA1c and P1NP were positively associated with the occurrence of NAFLD. CONCLUSIONS: The bone metabolic indicator P1NP might be a potential predicator for the diagnosis of NAFLD in clinical application.

[Role of adrenal vein sampling in differential diagnosis of primary aldosteronism subtypes].

Objective: To investigate the role of adrenal vein sampling (AVS) in identifying the subtype of primary aldosteronism (PA). Methods: AVS was performed in 50 patients who were confirmed as PA between September 2010 and September 2016 in Nanjing Drum Tower Hospital. Clinical, biochemical and follow-up data were reviewed retrospectively. Bilaterally simultaneous catheterization without cosyntropin stimulation and contemporaneous cortisol measurement during AVS were used. Selectivity index (SI)≥1.5 suggested that the sample was from the adrenal vein.Lateralization index (LI) ≥2 suggested unilateral disease.Clinical data was further compared and the AVS findings were analyzed. Results: AVS was successful performed in 41 cases of 50 patients, and the success rate was 82%. According to the results of AVS and postoperative pathology, 41 cases were divided into aldosterone-producing adenoma (APA)/unilateral adrenal hyperplasia (UAH) group (24 cases) and idiopathic hyperaldosteronism (IHA) group (17 cases). Compared with IHA group, patients with APA/UAH showed longer duration of hypertension[10.0 (5.0, 13.0) y vs 4.0 (2.0, 8.0) y, P=0.046], higher proportion of hypokalemia (95.8% vs 64.7%, P=0.009). Furthermore, patients with APA/UAH demonstrated lower plasma renin activity (P=0.089), higher plasma aldosterone concentration and aldosterone to renin ratio (ARR) (both P<0.05). The diagnostic concordance between CT and adrenal vein sampling was only 48.8%(20/41). Conclusions: The application of bilaterally simultaneous catheterization and contemporaneous cortisol measurement improves success rate and diagnostic accuracy of AVS. AVS is useful in subtype diagnosis of PA with equivocal imaging findings.

Translocation breakpoints of chromosome 1 in male carriers: clinical features and implications for genetic counseling.

Reciprocal translocation is closely associated with male infertility and recurrent miscarriages. Balanced reciprocal translocations associated with reproductive failures are predominantly observed on chromosome 1. Additionally, infertile male patients present a number of breakpoints throughout chromosome 1. A translocation breakpoint might interrupt the structure of an important gene, leading to male infertility. Here, we report the breakpoints on chromosome 1 translocation and the clinical features presented in carriers, to enable informed genetic counseling of these patients. Balanced reciprocal translocations were found in 1.57% of the tested patients. Among 82 patients, 23 patients (28.05%) were carriers of the chromosome 1 translocation: 12 presented pre-gestational infertility with clinical manifestations of azoospermia or oligozoospermia, while 11 patients presented gestational infertility (able to conceive but with a tendency to miscarry or give birth to a stillborn). The breakpoint at 1p22 was predominantly observed in these patients; additionally, breakpoints at 1p31.2, 1p10, and 1q25 were associated with gestational infertility. Breakpoints at 1p13, 1q12, and 1q21 were associated with pre-gestational infertility. These results suggested that breakpoints at 1p32, 1p13, and 1q21 were predominantly associated with pre-gestational infertility, while that at 1q25 was associated with gestational infertility. Chromosome 1 translocation carriers with infertility presenting as azoospermia or oligospermia should be counseled on chromosomal breakpoints and the different molecular technologies available to facilitate reproduction.

Efficacy and safety of combination therapy with vildagliptin and metformin versus metformin uptitration in Chinese patients with type 2 diabetes inadequately controlled with metformin monotherapy: a randomized, open-label, prospective study (VISION).

AIMS: To compare the efficacy and safety of combination of vildagliptin and metformin therapy with metformin uptitration in Chinese patients with type 2 diabetes (T2DM) inadequately controlled with low-dose metformin. METHODS: In this 24-week prospective, randomized, multicentre, open-label study, patients with T2DM inadequately controlled with metformin ≤1000 mg daily were divided 1 : 1 : 1 : 1 into four prespecified subgroups based on age and body mass index (BMI). Patients in each subgroup were randomized 5 : 1 to receive either vildagliptin (50 mg twice daily) plus metformin [500 mg twice daily; vildagliptin and low-dose metformin (VLDM) group] or metformin uptitration [1000 mg twice daily; high-dose metformin (HDM) group]. The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline at week 24. The key secondary endpoints included percentage of patients achieving target HbA1c without adverse gastrointestinal (GI) events and mean change in fasting plasma glucose (FPG) from baseline to week 24. RESULTS: A total of 3084 patients were randomized. HbA1c reduction of 0.54% at week 24 in the VLDM group was non-inferior and statistically superior compared with 0.40% in the HDM group (P < 0.0001). VLDM's non-inferiority to HDM was confirmed in the four subgroups and its superiority was shown for all subgroups (p < 0.05) except for the subgroup of patients aged <60 years with a BMI of ≥24 kg/m(2) . Compared with HDM, VLDM significantly increased the percentage of patients achieving HbA1c ≤6.5% and HbA1c ≤6.5% without GI events. FPG levels in the VLDM group were lower at week 24 numerically than in the HDM group. The two treatment arms had similar safety profiles. CONCLUSIONS: VLDM was non-inferior and statistically superior to HDM in glycaemic control in Chinese patients with T2DM inadequately controlled with low-dose metformin.

Epigenomic elements analyses for promoters identify ESRRG as a new susceptibility gene for obesity-related traits.

OBJECTIVES: With ENCODE epigenomic data and results from published genome-wide association studies (GWASs), we aimed to find regulatory signatures of obesity genes and discover novel susceptibility genes. METHODS: Obesity genes were obtained from public GWAS databases and their promoters were annotated based on the regulatory element information. Significantly enriched or depleted epigenomic elements in the promoters of obesity genes were evaluated and all human genes were then prioritized according to the existence of the selected elements to predict new candidate genes. Top-ranked genes were subsequently applied to validate their associations with obesity-related traits in three independent in-house GWAS samples. RESULTS: We identified RAD21 and EZH2 as over-represented, and STAT2 (signal transducer and activator of transcription 2) and IRF3 (interferon regulatory transcription factor 3) as depleted transcription factors. Histone modification of H3K9me3 and chromatin state segmentation of 'poised promoter' and 'repressed' were over-represented. All genes were prioritized and we selected the top five genes for validation at the population level. Combining results from the three GWAS samples, rs7522101 in ESRRG (estrogen-related receptor-γ) remained significantly associated with body mass index after multiple testing corrections (P=7.25 × 10(-5)). It was also associated with ß-cell function (P=1.99 × 10(-3)) and fasting glucose level (P<0.05) in the meta-analyses of glucose and insulin-related traits consortium (MAGIC) data set.Cnoclusions:In summary, we identified epigenomic characteristics for obesity genes and suggested ESRRG as a novel obesity-susceptibility gene.

Dynamics of bouncing-versus-merging response in jet collision.

A new regime of oblique jet collision, characterized by low impact inertia and jet merging through bridge formation, is observed and thereby completes the entire suite of possible jet collision outcomes of (soft) merging, bouncing, and (hard) merging with increasing inertia. These distinct regimes, together with the observed dependence of the collision outcome on the impact angle and liquid properties, are characterized through scaling analysis by considering the competing effects of impact inertia, surface tension, and viscous thinning of the interfacial air gap leading to merging.

The beneficial effect of metformin on ß-cell function in non-obese Chinese subjects with newly diagnosed type 2 diabetes.

AIM: Studies with metformin suggest a favourable change in ß-cell function over sulphonylureas in the early course of obese type 2 diabetes mellitus (T2DM), but it remains unclear whether a similar effect is observed in non-obese individuals. Here we investigated the effects of metformin or glipizide gastrointestinal therapeutics system extended-release formulation (GITS) on ß-cell function in non-obese patients with newly diagnosed T2DM. METHODS: A total of 160 newly diagnosed patients with fasting glucose 7.0-13.0 mmol/L and body mass index <30 kg/m(2) from five centres in China were randomized to metformin or glipizide GITS for 24 weeks. Early insulin secretion [the ratio of area under the curve (AUC) of insulin to glucose during 0-30 min (InsAUC30 /GluAUC30 )] and insulin sensitivity [Matsuda index (ISIM )] were assessed during the standard meal tolerance test before and after therapy. Plasma glucagon-like peptide-1(GLP-1) and glucagon levels were also measured. RESULTS: Metformin improved InsAUC30 /GluAUC30 significantly (from 8.1 ± 0.6 pmol/mmol to 10.7 ± 0.7 pmol/mmol, p < 0.05), comparable to results with glipizide GITS. In the metformin-treated lean (body mass index < 25 kg/m(2) ) subgroup, the increase in ISIM was not significant, but the improvement in InsAUC30 /GluAUC30 was of great magnitude. Increased GLP-1 responses during meal tolerance test and decreased fasting glucagon level were observed after metformin treatment. Correlation analysis showed that the improvement of InsAUC30 /GluAUC30 was associated with the changes in HbA1c (r = -0.374, p = 0.000), ISIM (r = 0.356, p = 0.001), and ΔGLP-10-30 (r = 0.225, p = 0.02). CONCLUSIONS: Metformin improved ß-cell function in non-obese subjects with newly diagnosed T2DM, which was partly independent of the change in insulin sensitivity in these subjects. This study provides evidence-based data to support metformin use in non-obese patients with T2DM as the first-line agent, which can improve both insulin sensitivity and ß-cell function.