Effects of somatostatin receptor ligands on bone metabolism in acromegaly / 中华内分泌代谢杂志

Objective:To investigate the effect of somatostatin receptor ligands (SRLs) on bone metabolism in patients with acromegaly.Methods:Retrospective analysis of clinical data of acromegaly patients( n=100) received surgery or SRLs alone for 3 months. The changes of growth hormone (GH), insulin-like growth factor-1 (IGF-1), osteocalcin (OC), N-mid fragment of osteocalcin (N-MID), amino-terminal peptide of type I procollagen (P1NP) and C-terminal peptide degradation product of type I collagen(CTX) were compared before and after treatment. Patients were divided into drug treatment group and surgical group according to treatment methods. According to the decline of GH after medication, patients in the drug treatment group were further divided into drug sensitive group and drug insensitive group. Results:The average dynamic GH and IGF-1 indexes in the drug treatment group were significantly decreased after treatment compared with before treatment (both P<0.05), and CTX was also significantly decreased after treatment [1.25 (0.67, 1.40) ng/mL vs 1.34 (0.57, 1.68) ng/mL, P<0.05]. The mean dynamic GH, IGF-1 index, OC, N-MID, P1NP, and CTX in surgical group were significantly decreased after treatment compared with before treatment (all P<0.01). In the surgical group, there was a positive correlation between GH difference (ΔGH) and N-mid difference (ΔN-MID; r=0.454, P=0.026), and there was a positive correlation between IGF-1 index difference (ΔIGF-1 index) and CTX difference (ΔCTX; r=0.339, P=0.036). After treatment, the mean dynamic GH, IGF-1 index, CTX, P1NP, and N-MID in drug treatment group were significantly higher than those in surgical group (all P<0.001). CTX and N-MID decreased significantly after treatment in drug sensitive group compared with drug insensitive group (35.3% vs 7.2%, P<0.001; 24.1% vs 11.8%, P<0.05), and ΔGH was positively correlated with ΔCTX ( r=0.328, P=0.004). Conclusion:SRLs treatment can reduce bone formation marker N-MID and bone resorption marker CTX, improving the high turnover state of bone metabolism in patients with acromegaly, which may attribute to the reduction of GH and IGF-1 levels.

Transcriptome changes upon Toll-like receptor 9 pathway activation in primary renal tubular epithelial cells / 中华危重病急救医学

Objective:To explore the effect of Toll-like receptor 9 (TLR9) signaling pathway activation on the transcriptome in the renal tubular cells.Methods:Mouse primary renal tubular epithelial cells were extracted and cultured. When the degree of cell fusion reached 80%, they were divided into two groups, which were added with 10 μL phosphate buffered saline (PBS, PBS control group) and TLR9 activator cytosine phosphate guanidine oligodeoxynucleotide (CpG-ODN) with a final concentration of 5 μmol/L (CpG-ODN treatment group). The RNA sequencing was performed on the Illumina platform after extraction. DEGseq software was used to analyze the differential expression of genes between the two groups. Goatools and KOBAS online software were used to analyze the differential genes involved signal pathways. Homer software was used to predict transcription factors.Results:Compared with the PBS control group, there were a total of 584 differentially expressed genes in the CpG-ODN treatment group, of which 102 were up-regulated and 482 were down-regulated. The most significantly enriched gene ontology (GO) terms of differentially expressed genes included response to interferon-β, defense response to virus and other inflammatory pathway. The most significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways included 2'-5'-oligoadenylate synthase activity, regulation of ribonuclease activity, negative regulation of virus life cycle, cellular response to interferon-βand defense response to protozoan. The results of transcription factor prediction showed that interferon regulatory factor 3 (IRF3) was the most significantly enriched transcription factor in the promoter sequence of differential genes; the most significant transcription factor downstream of TLR9 was IRF3, and other predicted transcription factors such as transcription factor 21 (TCF21), zinc finger protein 135 (ZNF135), and PR domain containing 4 (PRDM4) might be new candidates for TLR9 signaling pathway.Conclusion:CpG-ODN activates TLR9 signaling pathway, and primary renal tubular epithelial cells can directly respond to CpG-ODN stimulation and undergo transcriptome changes, which provides a basis for further research on the molecular mechanism of TLR9 pathway in sepsis induced acute kidney injury.

Gut-derived lipopolysaccharide promotes alcoholic hepatosteatosis and subsequent hepatocellular carcinoma by stimulating neutrophil extracellular traps through toll-like receptor 4

Background/Aims@#Binge drinking leads to many disorders, including alcoholic hepatosteatosis, which is characterized by intrahepatic neutrophil infiltration and increases the risk of hepatocellular carcinoma (HCC). Molecular mechanisms may involve the migration of bacterial metabolites from the gut to the liver and the activation of neutrophil extracellular traps (NETs). @*Methods@#Serum samples from both binge drinking and alcohol-avoiding patients were analyzed. Mouse models of chronic plus binge alcohol-induced hepatosteatosis and HCC models were used. @*Results@#A marker of NETs formation, lipopolysaccharide (LPS), was significantly higher in alcoholic hepatosteatosis and HCC patients and mice than in controls. Intrahepatic inflammation markers and HCC-related cytokines were decreased in mice with reduced NET formation due to neutrophil elastase (NE) deletion, and liver-related symptoms of alcohol were also alleviated in NE knockout mice. Removal of intestinal bacteria with antibiotics led to decreases in markers of NETs formation and inflammatory cytokines upon chronic alcohol consumption, and development of alcoholic hepatosteatosis and HCC was also attenuated. These functions were restored upon supplementation with the bacterial product LPS. When mice lacking toll-like receptor 4 (TLR4) received chronic alcohol feeding, intrahepatic markers of NETs formation decreased, and hepatosteatosis and HCC were alleviated. @*Conclusions@#Formation of NETs following LPS stimulation of TLR4 upon chronic alcohol use leads to increased alcoholic steatosis and subsequent HCC.

The upregulated intestinal folate transporters direct the uptake of ligand-modified nanoparticles for enhanced oral insulin delivery

Transporters are traditionally considered to transport small molecules rather than large-sized nanoparticles due to their small pores. In this study, we demonstrate that the upregulated intestinal transporter (PCFT), which reaches a maximum of 12.3-fold expression in the intestinal epithelial cells of diabetic rats, mediates the uptake of the folic acid-grafted nanoparticles (FNP). Specifically, the upregulated PCFT could exert its function to mediate the endocytosis of FNP and efficiently stimulate the traverse of FNP across enterocytes by the lysosome-evading pathway, Golgi-targeting pathway and basolateral exocytosis, featuring a high oral insulin bioavailability of 14.4% in the diabetic rats. Conversely, in cells with relatively low PCFT expression, the positive surface charge contributes to the cellular uptake of FNP, and FNP are mainly degraded in the lysosomes. Overall, we emphasize that the upregulated intestinal transporters could direct the uptake of ligand-modified nanoparticles by mediating the endocytosis and intracellular trafficking of ligand-modified nanoparticles via the transporter-mediated pathway. This study may also theoretically provide insightful guidelines for the rational design of transporter-targeted nanoparticles to achieve efficient drug delivery in diverse diseases.

The value of intravoxel incoherent motion magnetic resonance imaging and texture analysis for predicting BRAF gene mutation in rectal cancer / 中华消化外科杂志

Objective:To investigate the value of intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) and texture analysis for predicting BRAF gene mutation in rectal cancer.Methods:The clinical diagnositic trial was conducted. The clinicopathological data of 36 rectal cancer patients who were admitted to the First People's Hospital of Shangqiu from January 2016 to June 2021 were collected. There were 28 males and 8 females, aged (50±4)years. All the 36 patients were confirmed by pathological examination. After genetic testing, 12 patients with BRAF mutant type of BRAF V600E mutation were allocated into the mutation group, and 24 patients with BRAF wild type were allocated into the non-mutation group. All patients underwent MRI scan before surgery, and IVIM related post-processing images were received by Function Tool post-processing software. Observation indicators: (1) consistency test between observers of IVIM para-meters and texture parameters; (2) comparison of IVIM parameters on MRI between the two groups; (3) comparison of texture parameters on MRI between the two groups; (4) diagnostic efficacy of IVIM and texture parameters. The intraclass correlation coefficient (ICC) was used to evaluate the consistency between observers, with ICC >0.80 as good consistency. The average values of para-meters with ICC >0.80 were included for further analysis. Measurement data with normal distribu-tion were represented as Mean± SD, and comparison between groups was analyzed by the indepen-dent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was analyzed by the chi-square test. Comparison of ordinal data was analyzed by the non-parameter rank sum test. The texture parameters were combined using the Logistic regression model. Receiver operating charac-teristic curve was used to analyze the predictive performance and calculate the sensitivity and specificity. Results:(1) Consistency test between observers of IVIM parameters and texture parameters: the ICCs between two observers of IVIM parameters including apparent diffusion coefficient, diffusion related coefficient, perfusion-related diffusion coefficient and perfusion-related parameter were 0.91, 0.90, 0.91, 0.89, respectively. The ICCs of texture parameters including the minimum value, the maximum value, the 10th percentile and the 25th percentile between two observers were <0.80 while the ICCs of texture parameters including mean value, the 50th percentile, the 75th percentile, the 90th percentile, energy, entropy, skewness and kurtosis between two observers were >0.80. (2) Comparison of IVIM parameters on MRI between the two groups: IVIM parameters of diffusion related coefficient and perfusion-related parameter on MRI were (0.70±0.13)×10 -3 mm 2/s and 0.39±0.30 for the mutation group, versus (0.79±0.12)×10 -3 mm 2/s and 0.17±0.10 for the non-mutation group, showing significant differences between the two groups ( t=-2.17, 2.46, P<0.05). (3) Comparison of texture parameters on MRI between the two groups: the texture parameters of mean value and energy on diffusion related coefficient image were 0.54±0.23 and 0.00(0.00,0.01) for the mutation group, versus 0.77±0.34 and 0.01(0.00,0.01) for the non-mutation group, showing significant differences between the two groups ( t=-2.12, Z=-1.35, P<0.05). (4) Diagnostic efficacy of IVIM and texture parameters: the areas under the curve (AUCs) of diffusion related coefficient, perfusion-related parameter, IVIM parameters combination, mean value of diffu-sion related coefficient image, energy value of diffusion related coefficient image, texture parameters combination were 0.69[95% confidence interval ( CI) as 0.52-0.84], 0.76(95% CI as 0.59-0.88), 0.79(95% CI as 0.62-0.91), 0.71(95% CI as 0.52-0.85), 0.79(95% CI as 0.62-0.91), 0.84(95% CI as 0.68-0.94), which were all lower than the AUC of IVIM and texture parameters combination as 0.92(95% CI as 0.79-0.99). Conclusions:IVIM parameters and texture parameters of MRI can non-invasively predict the mutation status of BRAF gene in rectal cancer. The combination of IVIM and texture parameters has a better predictive efficacy.

Establishment of an intelligent cervical vertebrae maturity assessment system based on cone beam CT data / 浙江大学学报·医学版

To establish an intelligent cervical vertebra maturity assessment system, and to evaluate the reliability and clinical value of the system. Sixty children aged were recruited in the study. Lateral cephalometric radiograph and cone beam CT (CBCT) were taken at the same period. Based on the CBCT data, the system automatically extracted the patient's facial area through Otsu's method, intercepted the sagittal plane by three-dimensional least squares method, captured the second to fourth cervical vertebrae by superpixel segmentation. And then selected points were marked automatically through morphological algorithm and manual method. Consistency test was performed on the two sets of data to compare the reliability of automated cervical morphology capture. According to the parameters of morphological identification, positioning and staging algorithms were designed to form the intelligent cervical vertebra maturity assessment system. The cervical vertebra maturity was also judged manually on the lateral cephalometric radiograph. The weighted Kappa test and the Gamma correlation coefficient were subsequently applied to evaluate the consistency and correlation. The results showed that the cervical vertebra features automatically captured based on CBCT data had a high accuracy on the overall morphological recognition. In the prediction of 8 inflection points out of 13 points, there was no significant difference between automatic and manual method on both X and Y axes (all >0.05). The assessment results of the cervical vertebra maturity of the intelligent system had strong consistency and correlation with the manual recognition results (weighted Kappa value=0.877, Gamma value=0.991, both <0.05). The intelligent cervical vertebrae maturity assessment system based on CBCT data established in this study presents reliable outcome and high degree of automation, indicating that the system may be used clinically.

The prevalence and clinical characteristics of macroprolactinemia: A single center survey / 中华内分泌代谢杂志

Objective:To describe the prevalence and clinical characteristics of macroprolactinemia in hyperprolactinemia patients.Methods:Consecutive 111 outpatients diagnosed with hyperprolactinemia were included in this study. Macroprolactin was routinely screened using the polyethylene glycol(PEG) precipitation method. Recovery of monomeric prolactin less than 40% was defined as macroprolactinemia. Clinical characteristics were analyzed in this study.Results:Among the 111 cases included, 99 were female and 12 were male, with an average age of(32.2±7.9) years. There were 32 cases(28.8%) of macroprolactinemia and 28 of them with normal monomeric prolactin levels(simple macroprolactinemia). prolactin levels before precipitation in simple macroprolactinemia were significantly lower than those with true hyperprolactinemia[(49.81±23.58 vs 83.56±65.82) ng/mL, P<0.05]. No amenorrhea and infertility were observed in patients with simple macroprolactinemia. The clinical manifestations of prolonged menstruation, oligomenorrhea and galactorrhea in female patients accounted for 25.9%, 37.0%, and 7.4%, respectively. Imaging data were obtained in 92 cases. The prevalence of pituitary adenomas in simple macroprolactinemia and true hyperprolactinemia was 42.9% and 66.0%, respectively. Fifteen(46.8%) of the macroprolactinemia cases were receiving or had received bromocriptine treatment, and 66.7% of them failed to achieve normal prolactin levels during therapy. Conclusion:Macroprolactinemia might be common in clinical practice. Macroprolactin should be screened in hyperprolactinemia patients lack of amenorrhea and infertility, and with poor response to dopamine agonist therapy.

The moderating effect of social support on behavioral inhibition/activation system and internet addiction among college students / 中华行为医学与脑科学杂志

Objective:To explore the effect of behavioral inhibition/activation system on internet addiction among college students, and to investigate the moderating role of social support.Method:From May to June in 2019, a questionnaire survey was conducted on 630 college students in Tianjin by internet addiction questionnaire, social support rating scale and behavioral inhibition activation scale.SPSS 24.0 and PROCESS macro program were used to analyze the data and check the moderating effect.Results:(1)The score of internet addiction scale for college students(2.73±0.63) was negatively correlated with the scores of all dimensions of social support(objective support: 11.06±4.19, r=-0.35, P<0.01; subjective support: 22.14±4.26, r=-0.25, P<0.01; degree of support utilization: 8.22±2.26, r=-0.33, P<0.01), positively correlated with the behavioral inhibition(2.58±0.53, r=0.63, P<0.01) and activition system(2.55±0.43, r=0.53, P<0.01). The behavior inhibition/activation system positivly predicted Internet addiction behavior( β=0.48, 0.17, both P<0.01). (2)The three dimensions of social support played a moderating role between behavioral inhibition system, behavioral activation system and college students' Internet addiction problem( β=0.08-0.16, all P<0.05). Among them, the objective support had the greatest regulatory effect, and the degree of support utilization was the second. Conclusion:The behavior inhibition/activation system has an important influence on the Internet addiction behavior of college students, and social support plays a very important moderating role.

Prognostic value of preoperative red blood cell distribution width for hepatocellular carcinoma / 中华消化外科杂志

Objective:To investigate the prognostic value of preoperative red blood cell distribution width (RDW) for hepatocellular carcinoma (HCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 025 HCC patients who were admitted to three medical centers (586 in the First Affiliated Hospital of Xi'an Jiaotong University, 248 in the Second Affiliated Hospital of Xi'an Jiaotong University and 191 in the Qinghai University Affiliated Hospital) between April 2002 and August 2017 were collected. There were 809 males and 216 females, aged (54±11)years, with a range from 16 to 83 years. The average coefficient of variation of RDW (RDW-CV) of 1 025 patients was 14.3%. Of 1 025 patients, 347 cases had high RDW of RDW-CV >14.3%, and 678 had low RDW of RDW-CV ≤14.3%. Observation indicators: (1) clinico-pathological data of HCC patients; (2) influencing factors for prognosis of HCC patients; (3) follow-up and survival. (4) stratified analysis of independent influencing factors. Follow-up was performed by outpatient examination, telephone interview or internet interview to detect postoperative survival of patients up to October 2017. Measurment data with normal distribution were represented as Mean±SD, and measurment data with skewed distribution were described as M (range). Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test. The Graphpad Prism 7.0 was used to draw survival curves, and Log-rank test was used for survival analysis. Univariate and multivariate analyses were performed using the COX proportional hazard model. Results:(1) Clinicopathological data of HCC patients: cases with age ≤70 years or >70 years, cases without cirhhosis or with cirhhosis , cases of Child-Pugh grade A or Child-Pugh grade B or C, cases with the level of alpha fetoprotein (AFP) ≤200 μg/L or >200 μg/L, cases with single tumor or multiple tumors were 313, 34, 152, 186, 161, 53, 158, 143, 186, 109 for high RDW patients, versus 641, 37, 359, 310, 415, 48, 367, 227, 547, 131 for low RDW patients, respectively, showing significant differences in above indicators between the two groups ( χ2=6.709, 6.787, 23.906, 7.114, 34.375, P<0.05). (2) Influencing factors for prognosis of HCC patients: results of univariate analysis showed that age, Child-Pugh grade, AFP, RDW-CV, tumor diameter, the number of tumors were related factors for prognosis of patients ( hazard ratio=1.388, 1.432, 1.534, 1.455, 2.813, 1.505, 95% confidence interval as 1.004-1.920, 1.086-1.887, 1.263-1.864, 1.211-1.748, 2.293-3.450, 1.173-1.932, P<0.05 ). Results of multivariate analysis showed that age, RDW-CV, tumor diameter and the number of tumors were independent factors for prognosis of patients ( hazard ratio=1.020, 1.340, 2.427, 1.438, 95% confidence interval as 1.007-1.032, 1.027-1.749, 1.801-3.272, 1.057-1.956, P<0.05). (3) Follow-up and survival: 1 025 patients were followed up for 1-124 months, with a median follow-up time of 25 months. The median survival time was 23 months for high RDW patients, versus 44 months for low RDW patients, showing a significant difference in the overall survival between the two groups ( χ2=11.640, P<0.05). (4) Stratified analysis of independent influencing factors: the results of stratified analysis of 3 independent influencing factors including age, tumor diameter and the number of tumors showed that in the 954 patients with age ≤70 years, the median survival time was 25 months for high RDW patients, versus 48 months for low RDW patients, showing a significant difference in the overall survival between the two groups ( χ2=14.030, P<0.05). In the 71 patients with age >70 years, the median survival time was 11 months for high RDW patients, versus 29 months for low RDW patients, showing no significant difference in the overall survival between the two groups ( χ2=0.933, P>0.05). In the 459 patients with tumor diameter ≤5 cm, the median survival time was 44 months for high RDW patients, versus 76 months for low RDW patients, showing a significant difference in the overall survival between the two groups ( χ2=8.660, P<0.05). In the 487 patients with tumor diameter >5 cm, the median survival time was 14 months for high RDW patients, versus 18 months for low RDW patients, showing no significant difference in the overall survival between the two groups ( χ2=2.950, P>0.05). In the 733 patients with single tumor, the median survival time was 20 months for high RDW patients, versus 48 months for low RDW patients, showing a significant difference in the overall survival between the two groups ( χ2=13.530, P<0.05). In the 240 patients with multiple tumors, the median survival time was 15 months for high RDW patients, versus 20 months for low RDW patients, showing a significant difference in the overall survival between the two groups ( χ2=6.820, P<0.05). Conclusions:Preoperative RDW can be used as a predictive index for prognosis of HCC patients, and patients with high RDW have poorer prognosis. RDW have better predictive value in patients with age ≤70 years or tumor diameter ≤5 cm.

The impact of genetic and environmental regulation on the expression of antibiotic resistance genes in Enterobacteriaceae / 生物工程学报

Antibiotic resistance is a major global concern and challenge in the 21st century. Enterobacteriaceae are one of the important pathogens of hospital-acquired infections. With the increasing use of antibiotics in clinical practice, a variety of drug-resistant Enterobacteriaceae, especially multidrug-resistant Enterobacteriaceae have emerged, posing an increasingly serious threat to human health. Bacteria can acquire antibiotic resistance by mutation or horizontal transfer of antibiotic resistance genes, and it is often possible to predict the corresponding resistance phenotype from known mechanism. However, recent findings suggest that genetic background and environmental factors could alter the expression of specific resistance genes and that a given genotype does not always generate the expected resistance phenotype. The genotype-phenotype segregation greatly hampers our ability to predict antibiotic resistance phenotype from a genetic perspective. In this review, we explore the genetic and environmental regulation of the expression of antibiotic resistance genes in a variety of Enterobacteriaceae, with the aim to provide scientific evidence for genetic prediction of antibiotic resistance phenotype and clinical guidance on drug use.

Progress on diagnosis and treatment of sympathetic ophthalmia / 中华眼底病杂志

Sympathetic ophthalmia (SO) is a bilateral granulomatous uveitis that occurs after single eye surgery or internal eye surgery. Its pathogenesis is not yet clear, and it is mostly considered to be an immune disease caused by exposure to autoantigens. The clinical diagnosis mainly depends on the patient's medical history, typical clinical manifestations and signs, and auxiliary ophthalmic imaging examinations such as FFA, ICGA, OCT. The clinical manifestations of SO are complex and variable, and the disease is prone to relapse, which may eventually lead to blindness. At present, treatment is mainly through systemic glucocorticoid therapy combined with immunosuppressive agents and/or biological agents. Understanding the typical imaging manifestations of SO is helpful to confirm the diagnosis early in the clinic, and timely provide reasonable drug treatment to improve the prognosis of patients.

Synthesis and biological evaluation of a series of 2-(((5-akly/aryl-1-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimidin-4(3)-ones as potential HIV-1 inhibitors

A series of 2-(((5-akly/aryl-1-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimidin-4(3)-ones were synthesized and their anti-HIV-1 activities were evaluated. Most of these compounds were highly active against wild-type (WT) HIV-1 strain (IIIB) with EC values in the range of 0.0038-0.4759 μmol/L. Among those compounds, had an EC value of 3.8 nmol/L and SI (selectivity index) of up to 25,468 indicating excellent activity against WT HIV-1. anti-HIV-1 activity and resistance profile studies suggested that compounds and displayed potential anti-HIV-1 activity against laboratory adapted strains and primary isolated strains including different subtypes and tropism strains (ECs range from 4.3 to 63.6 nmol/L and 18.9-219.3 nmol/L, respectively). On the other hand, it was observed that those two compounds were less effective with EC values of 2.77 and 4.87 μmol/L for HIV-1A (K103N + Y181C). The activity against reverse transcriptase (RT) was also evaluated for those compounds. Both and obtained sub-micromolar IC values showing their potential in RT inhibition. The pharmacokinetics examination in rats indicated that compound has acceptable pharmacokinetic properties and bioavailability. Preliminary structure-activity relationships and molecular modeling studies were also discussed.

Advances in the effects on false lumen thrombosis after the endovascular treatment of aortic dissection and its intervention strategies / 中华外科杂志

Aortic dissection is a urgent and dangerous disease, and the endovascular treatments can cure it in an effective and efficient way. As an important indicator of aorta remodeling, false lumen thrombosis is related to the prognosis of aortic dissection after endovascular treatment. The relationships among false lumen thrombosis after endovascular treatment and prognosis of aortic dissection, and the clinical techniques that can promote the false lumen thrombosis are reviewed in this paper. The aim is to promote a comprehensive evaluation of aorta remodeling.

Finite Element Modeling and Analysis of Ventricular Septal Defect Occluders / 医用生物力学

Objective To analyze influences of the braiding angle and material on performance of ventricular septal defect (VSD) occluders, so as to provide theoretical basis and guidance for their design. Methods The finite element models of occluders with different braiding angles (30°, 45° and 60°) were developed respectively. The radial supporting and axial bending performances of nickel titanium (NiTi) occlude and poly-p-dioxanone (PPDO) occlude were then compared. Results Under 5 kPa radial loading, radial stiffness of the 30°, 45° and 60° NiTi occluder waists were 8.60, 1.51 and 0.99 mN/mm3,respectively, while that of 45° PPDO occluder waist was 7.35 mN/mm3. Under axial bending of 0.5 rad, the maximum radial deformation of the 30°, 45°, 60° NiTi occluder waists were 1.17, 1.24 and 0.22 mm, while that of the 45° PPDO was 0.54 mm. Conclusions Under the condition of using the same material, occluders with braiding angle of 60° show the lowest radial stiffness, indicating they have the best radial supporting ability. Furthermore, they also show the smallest maximum radial deformation, indicating they have the best axial bending ability and the compliance. On the other hand, under the condition of using the same braiding angle, NiTi occluders show lower radial stiffness, indicating they have better radial supporting ability. However, PPDO occluders show lower maximum radial deformation, indicating they have better axial bending ability and compliance.

Clinical efficacy of Scrophularia ningpoensis granules combined with fosinopril for congestive heart failure / 药学实践杂志

Objective To evaluate the efficacy of Scrophularia ningpoensis granules combined with fosinopril in treatment of congestive heart failure.Methods 60 congestive heart failure patients were randomly divided into 2 groups, 30 patients in the treatment group and 30 patients in the control group.Besides the conventional therapy, the control group was treated with fosinopril and the treatment group received Scrophularia ningpoensis granules plus fosinopril for 90 days.Left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular ejection fraction (LVEF) and serum B-type brain natriuretic peptide (BNP) were measured before and after treatment.Results The total effective rate in the treatment group and the control group were 90%, but significantly effective number in the treatment group was higher than the control group.The levels of BNP, LVEDD and LVESD in both groups were decreased, while LVEF was increased after the treatment.The difference was statistically significant (P<0.01).The degree of improvement of heart function in the treatment group was better than that in the control group (P<0.05).Conclusion The combination therapy of Scrophularia ningpoensis granules and fosinopril is efficacious in treating CHF.

The efficacy and safety of insulin degludec versus insulin glargine in insulin-naive subjects with type 2 diabetes: results of a Chinese cohort from a multinational randomized controlled trial / 中华内科杂志

Objective To compare the safety and efficacy of insulin degludec (IDeg) with those of insulin glargine (IGlar) in insulin-naive subjects with type 2 diabetes (T2DM).Methods This was a 26-week,randomized,open-label,parallel-group,treat-to-target trial in 560 Chinese subjects with T2DM (men/women:274/263,mean age 56 years,mean diabetes duration 7 years) inadequately controlled on oral antidiabetic drugs (OADs).Subjects were randomized 2:1 to once-daily IDeg (373 subjects) or IGlar(187 subjects),both in combination with metformin.The primary endpoint was changes from baseline in glycosylated hemoglobin(HbA1c) after 26 weeks.Results Mean HbA1c decreased from 8.2％ in both groups to 6.9％ in IDeg and 7.0％ in IGlar,respectively.Estimated treatment difference (ETD) of IDegIGlar in change from baseline was-0.10％ points (95％ CI-0.25-0.05).The proportion of subjects achieving HbA1c ＜ 7.0％ was 56.3％ and 49.7％ with IDeg and IGlar,respectively [estimated odds ratio of IDeg/IGlar:1.26 (95 ％ CI 0.88-1.82)].Numerically lower rateof overall confirmed hypoglycaemia and statistically significantly lower nocturnal confirmed hypoglycemia were associated with IDeg compared with IGlar,respectively [estimated rateratio of IDeg/IGlar 0.69 (95％ CI 0.46-1.03),and 0.43 (95％ CI 0.19-0.97)].No differences in other safety parameters were found between the two groups.Conclusions IDeg was non-inferior to IGlar in terms of glycaemic control,and was associated with a statistically significantly lower rate of nocturnal confirmed hypoglycaemia.IDeg is considered to be suitable for initiating insulin therapy in Chinese T2DM patients on OADs requiring intensified treatment.Clinical trail registration Clinicaltrials.gov,NCT01849289.

Effects of incretin class of antidiabetic drugs on lipid metabolism in patients with type 2 diabetes and its mechanism / 中华内分泌代谢杂志

Chronic hyperglycemia is often accompanied by abnormal lipid metabolism, hypertension, low-grade systemic inflammation and oxidative stress.These factors increase the risk of cardiovascular disease(CVD)in type 2 diabetes mellitus(T2DM)patients.Comprehensive treatment of T2DM should emphasize the improvement of abnormal lipid metabolism, prevention of weight gain and reduction of the CVD risk in addition to proper glycemic control.Incretin, as a new hypoglycemic drug, has more advantages in improving glucose and lipid metabolism, finally to reduce cardiovascular risk.Through possible mechanisms including direct influence on liver lipid metabolism, change of fat mobilization and delay of gastric emptying, incretin shows positive influence on the lipid metabolic markers such as low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, triglycerides, and total cholesterol, while it improves glucose control.Thus, incretin plays an important role in the comprehensive management of type 2 diabetes mellitus.

Mechanism of α-naphthyl isothiocyanate inducing cholestatic hepatitis: a preliminary study / 临床肝胆病杂志

ObjectiveTo investigate the mechanism of α-naphthyl isothiocyanate (ANIT) inducing cholestatic hepatitis. MethodsA total of 60 healthy male Sprague-Dawley rats were randomly divided into normal control group (N group with 30 rats) and model group (ANIT group with 30 rats), and each group was further divided into three subgroups according to different time phases after gavage (at 24, 48, and 72 hours after gavage), with 10 rats in each group. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), and total bilirubin (TBil) were measured, and the level of malondialdehyde (MDA) in the liver was measured. A light microscope was used to observe the pathological changes in the liver, and a transmission electron microscope was used to observe the changes in the ultrastructure of the bile canaliculus. A confocal laser scanning microscope was used to analyze the mean fluorescence intensity of phalloidine labeled by fluorescein isothiocyanate in order to determine the change in the level of fibrous actin (F-actin). ResultsAfter the administration of ANIT by gavage, the model group showed significant increases in the serum levels of ALT, AST, GGT, and TBil and the level of MDA in liver tissue compared with the normal control group. The model group also showed damage in the structure of the hepatic lobules, hyaline degeneration of hepatocytes, spotted, patchy, and focal necrotic lesions, and neutrophil infiltration mostly confined to the hepatocytes around the bile duct, proliferation of biliary epithelial and fibrous tissues, widened perisinusoidal spaces, dilation of the bile canaliculi, extensive shedding of microvilli, and formation of bile thrombi in the bile capillaries, as well as a low fluorescence intensity of F-actin. The above changes were the most obvious at 48 hours; recovery began at 72 hours, but significant differences were still seen between the two groups. ConclusionANIT can cause lipid peroxidation in liver tissue and lead to degeneration and necrosis of liver cells, damage of microvilli of the bile canaliculi, and formation of bile thrombi, as well as reduction in the expression of F-actin in the bile canaliculi. Therefore, it affects the function of the liver to secrete bile and causes cholestatic hepatitis.

Determination of Nine Residual Solvents in Grape Seed Extract by Headspace Gas Chromatography / 医药导报

Objective To establish a headspace gas chromatography method for determination of nine residual solvents in grape seed extract. Methods The residual solvents in grape seed extract were separated on DB-WAX column (30 m× 0.45 mm, 0.85 μm) with an FID detector; the injector temperature and the detector temperature was set at 220 ℃ and 250 ℃ , respectively; the chapiter pressure was 27.58 kPa; the containers of headspace injector were in equilibrium for 30 min at 80 ℃ ;the N, N-dimethylformamide was used as the solvent. Results The detected solvents were well separated. Good linear relationship of the benzene and ethanol was obtained within the range of 0.04-0.3,100-750 μg?mL-1 , respectively. Good linear relationships of the hexane, o-xylene, m-xylene, p-xylene, styrene, toluene and 1,2-diethyl benzene solvents were obtained within the range of 0.4-3.0 μg?mL-1 (r≥0.995 8), respectively. The average recoveries (n = 3) of the nine solvents were 96.35%,97.08%,97.31%,89.93%,92.35%,90.65%,88.56%,93.84%,86.51% and the RSDs were 4.38%,2.16%,3.49%, 4.19%,4.80%,4. 83%,4. 70%,5. 00%,4. 39%, respectively. Conclusion The established method is simple, rapid and accurate, which can be used for the determination of residual solvents in grape seed extract and can simultaneously provide scientific basic for quality control.

Determination of 2-Indole Ketone Derivative and Its Related Substances by High Performance Liquid Chromatography / 医药导报

Objective To establish an high performance liquid chromatography method for determination of 2-indole ketone derivative and its related substances. Methods Agilent Eclipse XDB-C18(250 mm×4.6 mm,5 μm) column was adopted.The mobile phase was acetonitrile-water with gradient elution mode at a flow rate of 1. 0 mL?min-1; the column temperature was 35 ℃;the injection volume was 20 μL and the detection wavelength was set at 257 nm. Results 2-indole ketone derivative ID and related substances could be well separated. The 2-indole ketone derivative had good linear correlation ( r=0.999 4) within the range of 40-300 μg?mL-1 . It had a good precision ( RSD<1%) . The limit of detection was 8 ng. Conclusion The method is accurate,simple,sensitive and selective,which can be used for the quality control of 2-indole ketone derivative and related substances.