Efficacy of Exenatide Administered Twice Daily in Body Mass Index Reduction in Patients with Type 2 Diabetes Mellitus.

Background: Exenatide is a glucagon-like peptide-1 receptor agonist that can reduce body weight. This study aimed to determine the efficacy of exenatide on body mass index (BMI) reduction in patients with type 2 diabetes mellitus (T2DM) with differing baseline body weight, blood glucose, and atherosclerotic status and to determine if there is a correlation between BMI reduction and cardiometabolic indices in these patients. Methods: This retrospective cohort study used data from our randomized controlled trial. A total of 27 T2DM patients treated with combination therapy of exenatide twice daily and metformin for 52 weeks were included. The primary endpoint was a change in the BMI from the baseline to week 52. The secondary endpoint was a correlation between BMI reduction and cardiometabolic indices. Findings. The BMIs of overweight and obesity patients and those with glycated hemoglobin (HbA1c) ≥ 9% significantly decreased -1.42 ± 1.48 kg/m2(P=0.015) and -0.87 ± 0.93 kg/m2(P=0.003), respectively, at the baseline after 52 weeks of treatment. There was no reduction in BMI in patients with normal weight, HbA1c <9%, the nonatherosclerosis group, and the atherosclerosis group. The decrease in BMI was positively correlated with changes in blood glucose, high-sensitivity C-reactive protein (hsCRP), and systolic blood pressure (SBP). Conclusion: BMI scores improved after exenatide treatment for 52 weeks in T2DM patients. Weight loss was affected by baseline body weight and blood glucose level. In addition, BMI reduction from the baseline to 52 weeks was positively correlated with baseline HbA1c, hsCRP, and SBP. Trial Registration. Chinese Clinical Trial Registry (ChiCTR-1800015658).

Association of exposure to per- and polyfluoroalkyl substances with hemoglobin and hematocrit during pregnancy.

BACKGROUND: Per- and polyfluoroalkyl substances (PFASs) are common environmental contaminants and are widely detected in humans. Previous studies have linked PFASs exposure to adverse birth outcomes. However, the association between maternal exposure to PFASs and hemoglobin (Hb) and hematocrit (HCT) remains unclear. OBJECTIVES: We aimed to explore the relationship between PFASs exposure with Hb and HCT during pregnancy. METHODS: The present birth cohort study included 1044 pregnant women from Wuhan, China. Maternal HCT and Hb were measured in the first, second and third trimesters, and 13 PFASs were detected in the cord sera. Mixed linear models and general linear regression were applied to analyze the association between each single PFASs and Hb and HCT. Weighted quantile sum (WQS) regressions were used to investigate the association between PFASs mixture and Hb and HCT during pregnancy. RESULTS: In single-PFAS models, 10 PFASs were positively associated with HCT and Hb across pregnancy (a 10-fold increase in PFASs was associated with 1.47-3.54 % change in HCT and 1.46-3.20 % change in Hb (All P-FDR < 0.05). In addition, Hb and HCT were more positively related to PFASs in the second and third trimesters rather than the first trimester. The association between PFASs exposure and maternal HCT and Hb was not significant in the iron supplementation group, whereas significant in the non-iron supplementation group. A significant interaction between iron supplementation and non-iron supplementation was also detected. WQS regressions showed that perfluorononanoic acid (PFNA) and perfluorohexane sulfonate (PFHxS) contributed most to the association between PFASs and HCT and Hb in the second and third trimesters, respectively. CONCLUSION: Maternal PFASs exposure was positive with serum Hb and HCT. Moreover, maternal iron supplementation may play a modifying effect in influencing the relationship between PFASs and HCT and Hb.

Comparison of the effects of twice-daily exenatide and insulin on carotid intima-media thickness in type 2 diabetes mellitus patients: a 52-week randomized, open-label, controlled trial.

BACKGROUND: Exenatide, a glucagon like peptide 1 analog, has been suggested to reduce the cardiovascular disease risk factors, such as body weight, blood pressure and subclinical atherosclerosis in patients with type 2 diabetes mellitus (T2DM). This was the first randomized, open-label, controlled trial to compare the effects of exenatide versus insulin on subclinical atherosclerosis, as assessed by carotid-intima media thickness (CIMT), in patients with T2DM. METHODS: A total of 66 patients with T2DM admitted from March 10, 2015 to June 20, 2017 in the Department of Endocrinology, Beijing Hospital were randomized to receive twice-daily exenatide or aspartate 70/30 insulin for 52 weeks. The primary endpoint was change from baseline in CIMT, and secondary endpoints included changes at week 52 from baseline in body weight, glycemic markers, lipid metabolism markers, blood pressure, C-reactive protein, fibrinogen, 8-hydroxydeoxyguanosine, irisin, and brain natriuretic peptide. RESULTS: Exenatide more significantly reduced the CIMT from baseline compared with insulin after 52 weeks, with a mean difference of - 0.14 mm (95% interval confidence: - 0.25, - 0.02; P = 0.016). Weight and body mass index were both significantly reduced in the exenatide group over 52 weeks. Exenatide reduced total lipoprotein and low-density lipoprotein cholesterol levels more significantly than insulin at weeks 16 and 40. Correlation analyses showed that CIMT was positively correlated with low-density lipoprotein cholesterol. CONCLUSIONS: Twice-daily exenatide could prevent atherosclerosis progression in patients with T2DM over a 52-week treatment period compared with insulin therapy. Trial registration Chinese Clinical Trial Registry ChiCTR-1800015658.

Bioinformatic analysis of peripheral blood miRNA of breast cancer patients in relation with anthracycline cardiotoxicity.

BACKGROUND: The current diagnostic methods and treatments still fail to lower the incidence of anthracycline-induced cardiotoxicity effectively. In this study, we aimed to (1) analyze the cardiotoxicity-related genes after breast cancer chemotherapy in gene expression database and (2) carry out bioinformatic analysis to identify cardiotoxicity-related abnormal expressions, the biomarkers of such abnormal expressions, and the key regulatory pathways after breast cancer chemotherapy. METHODS: Cardiotoxicity-related gene expression data (GSE40447) after breast cancer chemotherapy was acquired from the Gene Expression Omnibus (GEO) database. The biomarker expression data of women with chemotherapy-induced cardiotoxicity (group A), chemotherapy history but no cardiotoxicity (group B), and confirmatory diagnosis of breast cancer but normal ejection fraction before chemotherapy (group C) were analyzed to obtain the mRNA with differential expressions and predict the micro RNAs (miRNAs) regulating the differential expressions. The miRanda formula and functional enrichment analysis were used to screen abnormal miRNAs. Then, the Gene Ontology (GO) analysis was adapted to further screen the miRNAs related to cardiotoxicity after breast cancer chemotherapy. RESULT: The data of differential analysis of biomarker expression of groups A, B, and C using the GSE40447-related gene expression profile database showed that there were 30 intersection genes. The differentially expressed mRNAs were predicted using the miRanda and Target Scan software, and a total of 2978 miRNAs were obtained by taking the intersections. Further, the GO analysis and targeted regulatory relationship between miRNA and target genes were used to establish miRNA-gene interaction network to screen and obtain seven cardiotoxicity-related miRNAs with relatively high centrality, including hsa-miR-4638-3p, hsa-miR-5096, hsa-miR-4763-5p, hsa-miR-1273 g-3p, hsa-miR6192, hsa-miR-4726-5p and hsa-miR-1273a. Among them, hsa-miR-4638-3p and hsa-miR-1273 g-3p had the highest centrality. The PCR verification results were consistent with those of the chip data. There are differentially expressed miRNAs in the peripheral blood of breast cancer patients with anthracycline cardiotoxicity. Among them, hsa-miR-4638-3p and hsa-miR-1273 g-3p are closely associated with the onset of anthracycline cardiotoxicity in patients with breast cancer. The signaling pathway is mainly concentrated in TGF-ß signaling pathway and adhesion signaling pathway. CONCLUSIONS: Changes in expression of hsa-miR-4638-3p and hsa-miR-1273 g-3p may contribute to the detection of anthracyclines induced cardiac toxicity, and their potential function may be related to TGF-ß signaling pathway and adhesion signaling pathway.

Urinary Biomarker of Prenatal Exposure to Disinfection Byproducts, Maternal Genetic Polymorphisms in CYP2E1 and GSTZ1, and Birth Outcomes.

The effects of disinfection byproducts (DBPs) on adverse birth outcomes remain unsettled. Maternal genetic variants in relation to DBP metabolism may modify this effect. Pregnant women during late pregnancy (n = 1306) were included from a Chinese cohort. Maternal urinary trichloroacetic acid (TCAA) was measured as a biomarker of DBP exposure. Maternal genotyping was conducted in cytochrome P450 2E1 (CYP2E1; rs2031920, rs3813867, and rs915906) and glutathione S-transferase zeta-1 (GSTZ1; rs7975). The associations between maternal urinary TCAA and birth outcomes and statistical interactions between maternal exposure and genetic polymorphisms were estimated. We found that maternal urinary TCAA levels were associated with decreased birth weight (P for trend = 0.003) and ponderal index (P for trend = 0.004). Interaction analyses showed that maternal urinary TCAA in association with decreased birth weight was observed only among subjects with CYP2E1 rs3813867 GC/CC versus GG (Pint = 0.07) and associations with decreased birth length, ponderal index, and gestational age were observed only among subjects with GSTZ1 rs7975 GA/AA versus GG (Pint = 0.07, 0.02, and 0.02, respectively). Our results suggested that prenatal DBP exposure was negatively associated with birth weight and ponderal index, and maternal genetic polymorphisms in CYP2E1 and GSTZ1 might modify these associations.

Total cholesterol to high-density lipoprotein cholesterol ratio is a significant predictor of nonalcoholic fatty liver: Jinchang cohort study.

BACKGROUND: Some studies found out that TC/HDL-C ratio is a predictor of Cardiovascular disease (CVD) and Nonalcoholic fatty liver (NAFLD) is related to CVD. And some researches have already studied that Apolipoprotein B to Apolipoprotein A1 ratio (ApoB/ApoA1) and Triglyceride to High-density lipoprotein cholesterol ratio (TG/HDL-C) were both related with CVD and NAFLD, but few studied the association between TC/HDL-C ratio and NAFLD. So, we suspected the ratio was also related to NAFLD. The research aims to study the predictive value of TC/HDL-C to NAFLD and to help the early detection of NAFLD. METHODS: Based on the Jinchang Cohort, the study contained 32,121 participants. We assessed the incidence of NAFLD by the quartiles of TC, HDL-C and TC/HDL-C. Then, the does-response relationship between these indicators and the risk of NAFLD was obtained. Finally, the receiver operator characteristic curve (ROC) was applied to decide the predictive value of TC/HDL-C. RESULTS: Among the study participants, the cumulative incidence of NAFLD was 6.30% and the rate of dyslipidemia was 40.37%. The biochemical indicators of NAFLD had a difference with general population. The incidence of NAFLD raised with the quartiles of TC, TG and LDL-C raising, while decreased with the HDL-C' quartiles raising. After controlling confounding factors, TC and TC/HD-C had a positive relationship with NAFLD, while HDL-C had the opposite. Finally, the ROC analysis showed the area under the curve (AUC) of TC/HDL-C (0.645) was greater than TC (0.554), HDL-C (0.627) and Apolipoprotein B to Apolipoprotein A1 (ApoB/ApoA1) (0.613). CONCLUSIONS: The TC/HDL-C ratio has significant predictive value to NAFLD.

Improved small moving target detection method in infrared sequences under a rotational background.

The infrared image sequence contains both the rotational background and a moving target, causing great difficulties in target detection and the occurrence of massive false alarm rates. This paper proposes an improved method using an optical flow field, which can estimate and compensate for the rotational motion background, thus detecting a small moving target. First of all, we select the Shi-Tomasi angular points for image detection and represent the background rotation with the sparse optical flow field of a complete image. Then we use the least squares method to estimate the parameters of the perspective model of background rotation so as to reconstruct the background motion vector field and compensate for background rotation. Finally we detect the small moving target with the differential method and the morphological treatment. The experimental results verify that this method can accurately detect a small moving target against the violently rotational background and provide an idea for the target interception algorithm under the condition that an infrared imaging seeker is overlooking.

Safranal carried by nanostructured lipid vehicles inhibits generalized epilepsy in mice.

Safranal, a main component of Crocus sativus, is suggested to have neuroprotective effects. The aim of this study was to investigate the effect of safranal and nanostructured lipid vehicle (NLV) carried safranal in acute and chronic experimental mice models of epilepsy. In PILO acute seizure model, safranal dose-dependently extended latency to generalized seizure, decreased the highest seizure stages and the number of generalized seizures. Moreover, NLV carried safranal further enhanced the anti-seizure effect, which is comparable to the action of sodium valproate. Meanwhile, NLV carried safranal reduced and delayed the electroencephalogram spectra power after pilocarpine injection. In histological aspect, safranal dose-dependently reduced the loss of neurons induced by seizure and NLV system further improved this protection at the same dose. In MES acute model, safranal markedly increased the electroconvulsive threshold, where NLV further improved its effect. In PTZ chronic seizure model, NLV carried safranal significantly delayed the kindling rate of progress and the time it took to reach generalized seizures as compared to NLV control group. In conclusion, this study indicates that safranal inhibits generalized seizure in acute and chronic epilepsy models in mice and NLV can enhance this effect. So, NLV carried safranal may have potential value in treatment of generalized epilepsy.

Heavy Metal Assessment among Chinese Nonferrous Metal-exposed Workers from the Jinchang Cohort Study.

Environmental exposure to heavy metals has been linked to a wide range of human health hazards. We detected the levels of 15 metals in urine samples from 500 representative sub-samples in an ongoing occupational cohort study (Jinchang Cohort) to directly evaluate metal exposure levels. Fifteen metals, namely As, Ba, Be, Cd, Cs, Cr, Co, Cu, Pb, Mn, Ni, Se, Tl, U, and Zn, were detected by inductively coupled plasma quadruple mass spectrometry. The results showed that median creatinine adjustment and geometric mean urinary metal levels were higher in the heavy metal-exposed group, except Se and Zn, than other reported general or occupational populations. Further studies should address the effects of heavy metals on human health.

Dynamic Changes in DNA Damage and Repair Biomarkers with Employment Length among Nickel Smelting Workers.

Our study explored the dynamic changes in and the relationship between the DNA damage marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) and the DNA repair marker 8-hydroxyguanine DNA glycosidase 1 (hOGG1) according to the length of occupational employment in nickel smelting workers. One hundred forty nickel-exposed smelting workers and 140 age-matched unexposed office workers were selected from the Jinchang cohort. The 8-OHdG levels in smelting workers was significantly higher than in office workers (Z=-8.688, P<0.05) and the 8-OHdG levels among nickel smelting workers in the 10-14 y employment length category was significantly higher than among all peers. The hOGG1 levels among smelting workers were significantly lower than those of non-exposed workers (Z=-8.948, P<0.05). There were significant differences between employment length and hOGG1 levels, with subjects employed in nickel smelting for 10-14 y showing the highest levels of hOGG1. Correlation analysis showed positive correlations between 8-OHdG and hOGG1 levels (r=0.413; P<0.01). DNA damage was increased with employment length among nickel smelting workers and was related to the inhibition of hOGG1 repair capacity.

Metal Exposure and Risk of Diabetes and Prediabetes among Chinese Occupational Workers.

OBJECTIVE: To study the association between metal exposure and risk of diabetes and prediabetes among Chinese workers exposed to metals. METHODS: We used data obtained from the baseline survey of the Jinchang Cohort Study of workers in Jinchang Industry, the largest nickel production company in China. A total of 42,122 workers ⋝20 years of age were included in the study. A standardized, structured questionnaire was used to collect epidemiological information. Physical examinations and laboratory tests were conducted to evaluate the health status of the participants and to measure various biomarkers including blood sugar, lipids, and urinary metal concentrations. Logistic regression was used to study the association between occupational groups categorized according to the measured metal levels (office workers, low-level; mining/production workers, mid-level; and smelting/refining workers, high-level) and risk of diabetes and prediabetes. RESULTS: The overall prevalence of diabetes and prediabetes was 7.5% and 16.8%, respectively. The adjusted odds ratios for diabetes among mining/production workers and smelting/refining workers compared to office workers were 1.5 (95% CI: 1.3, 1.7) and 3.8 (95% CI: 3.4, 4.3), respectively. No association was observed between these occupational groups and prediabetes in this study. CONCLUSION: Occupations associated with higher levels of metal exposure were associated with an increased risk of diabetes in this cohort. More studies are needed to confirm this observed association.

Trend Analysis of Cancer Mortality in the Jinchang Cohort, China, 2001-2010.

OBJECTIVE: To describe the baseline data of cancers in the Jinchang Cohort, this paper examined trends in cancer mortality among adults investigated in Jinchang, Gansu province from 2001 to 2010. METHODS: Mortality data were collected from company departments through administrative documents, death certificates, etc. Trend analyses of cancer mortality were performed on the basis of 925 cancer deaths between 2001 and 2010. RESULTS: The crude mortality rate of cancer continuously increased from 161.86 per 100,000 in 2001 to 315.32 per 100,000 in 2010, with an average increase of 7.69% per year in the Jinchang Cohort (16.41% in females compared to 6.04% in males), but the age-standardized mortality rate increased only in females. Thirteen leading cancers accounted for 92.10% of all cancer deaths. The five leading causes of cancer mortality in males were lung, gastric, liver, esophageal, and colorectal cancer, whereas those in females were lung, liver, gastric, breast, and esophageal cancer. CONCLUSION: The overall cancer mortality rate increased from 2001 to 2010 in the Jinchang Cohort, with greater rate of increase in females than in males. Lung, breast, and gastric cancer, in that order, were the leading causes of increased cancer mortality in females.

Nickel-exposed workers in China: a cohort study.

There are more than 50 000 workers in Jinchuan Group Co, Ltd (JNMC). Since all staff in JNMC are eligible for a medical examination every two years, only 23 484 nickel-exposed subjects who participated in medical examination were included in this study. Their data, collected from June 22, 2011 to September 28, 2012, in a comprehensive epidemiological survey and during medical examinations, permitted an extensive evaluation of the relation between metal exposure, gene, epigenetics and risk of human diseases. Their lifestyle investigation showed that the overall prevalence of current smokers, alcohol drinkers, and tea drinkers was 39.1%, 19.7%, and 55.2%, respectively. The prevalence of hypertension, allergic rhinitis and cholecystitis , the top 3 prevalent diseases, was 11.7%, 11.0%, and 8.9%, respectively.

Prevalence of metabolic syndrome in Chinese nickel-exposed workers.

The prevalence of metabolic syndrome (MS) was investigated in Chinese nickel-exposed workers. A total of 35 104 subjects were enrolled in this study. The age-adjusted prevalence of MS, BMI⋝25, diabetes, hypertension, and abnormal lipid was 13.9%, 29.5%, 12.8%, 27.5%, and 47.1%, respectively. The prevalence of BMI⋝25, hyperglycemia, and hypertension increased with the age of males and females, and was higher in males than in females (37.1% vs 21.5%, 15.9% vs 12.1%, 35.0% vs 24.3%, 54.3% vs 40.4%).

Evaluation of ultrasound and pulsed electric field combinations on the cooking Losses, texture Profile, and Taste-Related amino acids of chicken breast meat.

The search to improve the quality of meat while maintaining its nutritional value and flavor profile has driven the investigation of emerging clean-label non-thermal technologies in the field of meat processing. Ultrasound (US) and pulsed electric field (PEF) treatments have emerged as promising tools for producing high-quality meat products. This study investigated the combined effects of ultrasound and PEF on chicken breast meat quality, focusing on cooking loss, texture, and taste-related amino acids. Ultrasound (24.5 kHz, 300 W, 10 min) combined with PEF for 30 s (1.6, 3.3, and 5.0 kV/cm as US + PEF 1, US + PEF 3, and US + PEF 5, respectively) significantly reduced cooking losses (up to 28.78 %), potentially improving the product yield. Although US + PEF significantly (p < 0.05) affected pH, particularly at a higher PEF intensity (5 kV/cm), the overall color appearance of the treated meat remained unchanged. The combined treatments resulted in a tenderizing effect and decreased meat hardness, adhesiveness, and chewiness. Interestingly, US + PEF with increasing PEF intensity (1.6 to 5.0 kV/cm) led to a gradual increase in taste-related amino acids (aspartic acid, glutamic acid, etc.), potentially enhancing flavor. FTIR spectra revealed alterations in protein and lipid structures following treatment, suggesting potential modifications in meat quality. Scanning electron microscopy (SEM) revealed significant changes in the texture and structure of US + PEF-treated meat, depicting structural disruptions. Furthermore, Pearson's correlation analysis and principal component analysis (PCA) revealed a clear relationship between the physicochemical characteristics, free amino acids, color, and texture attributes of chicken meat. By optimizing treatment parameters, US + PEF could offer a novel approach to improve chicken breast meat quality.

Design strategy and research progress of multifunctional nanoparticles in lung cancer therapy.

INTRODUCTION: Lung cancer is one of the cancer types with the highest mortality rate, exploring a more effective treatment modality that improves therapeutic efficacy while mitigating side effects is now an urgent requirement. Designing multifunctional nanoparticles can be used to overcome the limitations of drugs and conventional drug delivery systems. Nanotechnology has been widely researched, and through different needs, suitable nanocarriers can be selected to load anti-cancer drugs to improve the therapeutic effect. It is foreseeable that with the rapid development of nanotechnology, more and more lung cancer patients will benefit from nanotechnology. This paper reviews the merits of various multifunctional nanoparticles in the treatment of lung cancer to provide novel ideas for lung cancer treatment. AREAS COVERED: This review focuses on summarizing various nanoparticles for targeted lung cancer therapy and their advantages and disadvantages, using nanoparticles loaded with anti-cancer drugs, delivered to lung cancer sites, enhancing drug half-life, improving anti-cancer drug efficacy and reducing side effects. EXPERT OPINION: The delivery mode of nanoparticles with superior pharmacokinetic properties in the in vivo circulation enhances the half-life of the drug, and provides tissue-targeted selectivity and the ability to overcome biological barriers, bringing a revolution in the field of oncology.

[Chemical Composition and Characterization of Nitroaromatic Compounds in Urban Areas of Shanghai].

The compositional characteristics, concentration of nitroaromatic compounds(NACs) in PM2.5 in urban Shanghai, and their correlation with gaseous precursors were investigated. A total of 39 winter and 46 summer PM2.5 samples from 2020 to 2021 were collected using a high-flow sampler and analyzed via ultra-performance liquid chromatography coupled with ESI-Orbitrap high-resolution mass spectrometry(UPLC-Orbitrap-HRMS). Quantitative analysis was performed on 12 NACs compounds, combined with backward trajectory meteorological elements, molecular composition, and classification analysis of CHON substances. The results showed that a total of 12 NACs had an average concentration in winter of 17.1 ng·m-3, which was three times higher than that in summer(5.7 ng·m-3), mainly due to air masses in winter coming primarily from the northern part of China with more biomass burning, whereas more air masses in summer came from the cleaner southeastern ocean. 4-Nitrophenol was the most abundant species of NACs in winter, whereas 4-nitrophenol(clean days) and 4-hydroxy-3-nitrobenzoic acid(polluted days) were the most abundant species in summer. Qualitative analysis based on features such as aromatic ring equivalence number(Xc), O/C, and H/C values for the identification and characterization of monocyclic and polycyclic aromatic compounds showed that CHON compounds were mainly aromatic compounds in winter and summer in urban Shanghai. The number and abundance of CHON compounds detected on PM2.5 polluted days were 2 and 1.5 times higher(winter) and 2.5 and 2 times higher(summer) than that on clean days, respectively. Comparing the analysis results of clean and polluted days in winter and summer, it was found that 80% of the CHON compounds with a relative abundance in the top 10 had O/N ≥ 3 and RDBE values between 5 and 8. The results suggest that these highly abundant CHON analogs may have had mononitro- or dinitro-substituted benzene rings. Correlation analysis between gaseous precursors and NACs indicated that oxidative reactive formation of VOCs(benzene, toluene, etc.) from anthropogenic emissions was the main source of NACs in summer. By contrast, it was influenced by a combination of biomass combustion emissions and secondary formation of oxidative NOx from anthropogenic VOCs in winter.

Antiatherogenic and Anti-Ischemic Properties of Traditional Chinese Medicine Xinkeshu via Endothelial Protecting Function.

Including herbal medicine, complementary and alternative medicine (CAM) is popular worldwide. The traditional Chinese medicine xinkeshu has been widely used to treat coronary heart disease in China. This study was designed to investigate the protective effect and probable mechanism of xinkeshu tablet to atherosclerotic myocardial ischemia rabbit. Rabbits were divided into four groups (n = 12 each) and fed with different diet for 12 weeks: Control (standard diet), Model (high-cholesterol diet), XKS (high-cholesterol diet with 184.8 mg/kg/d xinkeshu), and Atorvastatin (high-cholesterol diet with 5.0 mg/kg/d atorvastatin). Plasma lipoprotein, ECG, endothelium-dependent vessel relaxation, histomorphological study, and expressions of eNOS and VCAM-1 on coronary arteries were assessed. The findings showed that, similar to atorvastatin, xinkeshu presented significant effects on rescuing endothelium-dependent vessel relaxation, inhibiting atherosclerotic progress, preventing myocardial ischemia, and changing eNOS and VCAM-1 expression. However, xinkeshu showed no lipoprotein lowering effect in hypercholesterolemia rabbits. The results of the present study indicated that xinkeshu exerted potent antiatherogenic and anti-ischemic properties on atherosclerotic myocardial ischemia rabbit. An endothelial protecting effect may be involved in the mechanism other than antihyperlipidemic effect.

Comparing the effects of twice-daily exenatide and insulin on renal function in patients with type 2 diabetes mellitus: secondary analysis of a randomized controlled trial.

This is a secondary analysis of a randomized controlled trial (RCT) on the effects of the glucagon-like peptide-1 receptor agonists exenatide and insulin aspartate 30 injection on carotid intima-media thickness. Here, we report the renal outcomes of the intervention in patients with type 2 diabetes mellitus (T2DM). Data from the RCT study was used to evaluate the effect of exenatide or insulin given for 52 weeks on estimated glomerular filtration rate (eGFR) in patients with T2DM. The primary end point was the change in the eGFR from baseline between the exenatide and insulin groups in normal versus overweight patients and patients with obesity. The secondary end point was the correlation between change in eGFR and oxidative stress, glycemic control, and dyslipidemia. There was a significant difference in eGFR between the insulin and exenatide groups at 52 weeks (p=0.0135). Within the insulin group, the eGFR remained below baseline at 52 weeks in all patients, and there was an increase in body weight in the normal group compared with the overweight patients and patients with obesity. The opposite was observed in the exenatide group. A decrease in body weight was prominent in the exenatide group at 52 weeks (p<0.05), the eGFR was below baseline in overweight patients and patients with obesity and significantly above baseline in the normal group (p<0.05). The eGFR was positively correlated to 8-oxo-7,8-dihydroguanosine in the insulin group (p<0.05) but not the exenatide group. It can be concluded that compared with insulin, exenatide may improve renal function in overweight patients and patients with obesity more than in normal-weight patients with T2DM, but a further RCT is needed to confirm this effect.

Compassionate Use of Yuanjiang Decoction, a Traditional Chinese Medicinal Prescription, for Symptomatic Bradyarrhythmia.

Background: No effective medication is available for symptomatic bradyarrhythmia, particularly in low socioeconomic status (SES) population. Objective: To explore the safety and efficacy of Yuanjiang decoction, a traditional Chinese medicinal prescription, for symptomatic bradyarrhythmia on a compassionate-use basis. Methods: This compassionate-use study was conducted in Beijing, China between January 2019 and January 2020. Eligible participants were recruited and treated with Yuanjiang decoction (composed of 6 Chinese herbal medicines), 200 ml twice daily for 16 weeks. Analyses were done with the intention-to-treat (ITT) approach. The primary outcome measure was the proportion of participants who achieved a favorable treatment outcome at 16 weeks. Results: As of January 2020, 184 patients were included. After 16-weeks treatment, 12 participants were lost to contact while 21 participants were terminated from this study, with a drop-out rate of 17.93%. The most common treatment-related adverse events were xerostomia (6.52%), constipation (6.45%) and sleepiness (3.26%). The proportion of participants with favorable treatment outcome was 65.22% at 4 weeks, 59.78% at 8 weeks (OR: 1.11, 95% CI: 0.71-1.73), 61.41% at 12 weeks (OR: 1.16, 95% CI: 0.92-1.45) and 60.87% at 16 weeks (OR: 1.15, 95% CI: 0.98-1.35). In the multifactor regression analysis, the favorable treatment outcome at 16 weeks was significantly associated with completing at least 8 weeks treatment (OR: 2.053, 95% CI: 1.064-3.560), while unfavorable treatment outcome was significantly associated with an atrioventricular block (OR: 0.255, 95% CI: 0.083-0.784), current smoking (OR: 0.343, 95% CI: 0.027-0.487), and syncope in the month before treatment (OR: 0.321, 95%CI: 0.114-0.904). Conclusion: This compassionate-use study showed encouraging outcomes of treatment with Yuanjiang decoction, without serious adverse events. This study identified several key factors that may affect outcomes. These findings helped inform the design and assess the feasibility of a large-scale randomized clinical trial.