Global Trends and Frontier in Research on Pancreatic Alpha Cells: A Bibliometric Analysis from 2013 to 2023.

PURPOSE: Over the past 20 years, much of the research on diabetes has focused on pancreatic beta cells. In the last 10 years, interest in the important role of pancreatic alpha cells in the pathogenesis of diabetes, which had previously received little attention, has grown. We aimed to summarize and visualize the hotspot and development trends of pancreatic alpha cells through bibliometric analysis and to provide research direction and future ideas for the treatment of diabetes and other islet-related diseases. METHODS: We used two scientometric software packages (CiteSpace 6.1.R6 and VOSviewer1.6.18) to visualize the information and connection of countries, institutions, authors, and keywords in this field. RESULTS: A total of 532 publications, published in 752 institutions in 46 countries and regions, were included in this analysis. The United States showed the highest output, accounting for 39.3% of the total number of published papers. The most active institution was Vanderbilt University, and the authors with highest productivity came from Ulster University. In recent years, research hotspots have concentrated on transdifferentiation, gene expression, and GLP-1 regulatory function. Visualization analysis shows that research hotspots mainly focus on clinical diseases as well as physiological and pathological mechanisms and related biochemical indicators. CONCLUSIONS: This study provides a review and summary of the literature on pancreatic alpha cells through bibliometric and visual methods and shows research hotspot and development trends, which can guide future directions for research.

Risky-Driving-Image Recognition Based on Visual Attention Mechanism and Deep Learning.

Risky driving behavior seriously affects the driver's ability to react, execute and judge, which is one of the major causes of traffic accidents. The timely and accurate identification of the driving status of drivers is particularly important, since drivers can quickly adjust their driving status to avoid safety accidents. In order to further improve the identification accuracy, this paper proposes a risky-driving image-recognition system based on the visual attention mechanism and deep-learning technology to identify four types of driving status images including normal driving, driving while smoking, driving while drinking and driving while talking. With reference to ResNet, we build four deep-learning models with different depths and embed the proposed visual attention blocks into the image-classification model. The experimental results indicate that the classification accuracy of the ResNet models with lower depth can exceed the ResNet models with higher depth by embedding the visual attention modules, while there is no significant change in model complexity, which could improve the model recognition accuracy without reducing the recognition efficiency.

Efficacy and safety of liraglutide in type 2 diabetes mellitus patients complicated with coronary artery disease: A systematic review and meta-analysis of randomized controlled trials.

To evaluate the efficacy and safety of liraglutide in patients with Type 2 Diabetes Mellitus (T2DM) complicated with Coronary Artery Disease (CAD), we searched PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Chinese VIP Information (VIP), Wanfang Database and Chinese Biomedical Literature database (CBM) for relevant randomized controlled trials (RCTs) from inception to 7 October 2020. A total of 18 RCTs including 1557 patients with T2DM complicated with CAD were included. Meta-analysis revealed liraglutide reduced hemoglobin A1c (HbA1c) (WMD = -0.67; 95% CI[-0.94 to -0.39]; P < 0.00001), fasting plasma glucose (FPG) (WMD = -0.80; 95% CI[-1.06 to -0.54]; P < 0.00001) and 2 h plasma glucose (2hPG) (WMD = -1.64; 95% CI[-2.12 to -1.16]; P＜0.00001); improved left ventricular ejection fraction(LVEF) (WMD = 4.79; 95% CI[4.08-5.51]; P < 0.00001), left ventricular end-diastolic diameter (LVEDD) (WMD = -5.70; 95% CI[-6.67 to -4.72]; P＜0.00001), E/A (WMD = 0.13; 95% CI[0.11-0.14]; P < 0.00001) and left ventricular posterior wall thickness (LVPWT) (WMD = -1.86; 95% CI[-2.16 to -1.55]; P < 0.00001); reduced total cholesterol (TC) (WMD = -0.48; 95% CI[-0.56 to -0.39]; P < 0.00001), triglycerides (TG) (WMD = -0.42; 95% CI[-0.59 to -0.26]; P < 0.00001), low-density lipoprotein cholesterol (LDL-C) (WMD = -0.41; 95% CI[-0.55 to -0.26]; P < 0.00001), and increased high-density lipoprotein cholesterol (HDL-C) (WMD = -0.19; 95% CI[0.13-0.24]; P = 0.0005). As for safety assessment, liraglutide did not increase the incidence of hypoglycemia (OR = 0.75, 95% CI[0.32-1.77], P = 0.51) and gastrointestinal (OR = 1.15, 95% CI[0.72-1.85], P = 0.55) events. Consequently, liraglutide had favorable effects on blood glucose, cardiac function, lipid profile and an acceptable safety profile.

Systematic identification and analysis of dysregulated miRNA and transcription factor feed-forward loops in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease. Although some genes and miRNAs related with HCM have been studied, the molecular regulatory mechanisms between miRNAs and transcription factors (TFs) in HCM have not been systematically elucidated. In this study, we proposed a novel method for identifying dysregulated miRNA-TF feed-forward loops (FFLs) by integrating sample matched miRNA and gene expression profiles and experimentally verified interactions of TF-target gene and miRNA-target gene. We identified 316 dysregulated miRNA-TF FFLs in HCM, which were confirmed to be closely related with HCM from various perspectives. Subpathway enrichment analysis demonstrated that the method was outperformed by the existing method. Furthermore, we systematically analysed the global architecture and feature of gene regulation by miRNAs and TFs in HCM, and the FFL composed of hsa-miR-17-5p, FASN and STAT3 was inferred to play critical roles in HCM. Additionally, we identified two panels of biomarkers defined by three TFs (CEBPB, HIF1A, and STAT3) and four miRNAs (hsa-miR-155-5p, hsa-miR-17-5p, hsa-miR-20a-5p, and hsa-miR-181a-5p) in a discovery cohort of 126 samples, which could differentiate HCM patients from healthy controls with better performance. Our work provides HCM-related dysregulated miRNA-TF FFLs for further experimental study, and provides candidate biomarkers for HCM diagnosis and treatment.

[Expert consensus statement on treatment of type 2 diabetes with Xiaoke Pills in clinical practice].

Xiaoke Pills are Chinese and Western medicine compound preparations with effects of nourishing kidney and Yin,and supplementing Qi and promoting fluid. It is widely used in clinical treatment of type 2 diabetes( Qi and Yin deficiency syndrome),and continuously included in 2010,2013 and 2017 editions of Chinese prevention guide for type 2 diabetes. For the purpose of accurate positioning and rational use in clinic,it is necessary to further define the curative effect,indications,medication precautions and contraindications of Xiaoke Pills,in order to improve medication safety. This consensus was reached by reference of international clinical guidelines and expert consensus approach based on clinical evidence-based evidence,expert experience and standard specification. The evidence-based evaluation was oriented to clinical problems summarized by no less than 200 front-line clinical physicians in two rounds.GRADE system was adopted for quality classification and evaluation of the evidences,and then the nominal group method was used to form consensus recommendations or suggestions. This consensus defined the curative effect advantages,target users,dosage,administration method,contraindications and precautions of Xiaoke Pills,and provided valuable reference for the clinical use of the drug. Thisconsensus still needs to be updated and revised based on new clinical problems and evidence-based evidence in practical application in the future.

Circulating MicroRNA-146a and MicroRNA-21 Predict Left Ventricular Remodeling after ST-Elevation Myocardial Infarction.

OBJECTIVES: MicroRNA (miR)-146a and miR-21 have been reported to participate in inflammatory reactions and fibrosis.Excessive inflammation and cardiac fibrosis may play important roles in the development of left ventricular remodeling(LVR). This study assessed whether miR-146a, miR-21 and other biomarkers could predict LVR after myocardial infarction(MI). METHODS: Circulating miR-146a, miR-21 and other biomarker levels were measured in 198 patients with acute MI 5 days after primary percutaneous coronary intervention(PCI). All patients were assessed by transthoracic echocardiography on day 5 and 1 year after primary PCI. RESULTS: Concentrations of circulating miR-146a, miR-21, C-reactive protein, creatine kinase MB type and troponin I, as well as estimated glomerular filtration rate (eGFR) and left ventricular ejection fraction (LVEF), were significantly higher in patients with than in those without LVR (p < 0.05). Multivariate logistic regression analysis showed that circulating miR-146a (odds ratio, OR = 2.127, p < 0.0001), miR-21 (OR = 1.119,p < 0.0001), eGFR (OR = 0.939, p = 0.0137) and LVEF (OR =0.802, p = 0.0048) were independent predictors of LVR development. The area under the curve for the combination of miR-146a and miR-21 was significantly higher than for either alone. CONCLUSION: Circulating miR-146a and miR-21 may be novel biomarkers predictive of LVR after acute MI. Their combination may better predict LVR than either alone.

A Prospective, Multicentered, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Keluoxin Capsules in the Treatment of Microalbuminuria in Patients with Type 2 Early Diabetic Kidney Disease.

Background: To evaluate the efficacy and safety of Keluoxin (KLX) capsules and provide validated evidence for the application of KLX in the treatment of diabetic kidney disease (DKD). Methods: A multicenter, randomized, double-blind, placebo-controlled trial design was used to screen 129 patients with DKD (urinary albumin-to-creatinine ratio [UACR]: male, 2.5-30 mg/mmol; female, 3.5-30 mg/mmol) and with Qi and Yin deficiency and blood stasis symptoms. Written informed consent was obtained from all patients. The patients were randomly divided into KLX and control groups. The KLX group was orally administered KLX (6 g/day) and irbesartan tablets (150 mg/day), whereas the control group was administered KLX placebo (6 g/day) and irbesartan tablets (150 mg/day). Patients were observed for 24 weeks to evaluate the natural logarithm of the UACR (log-UACR), the odds ratio (OR) for a sustained increase in the UACR of at least 30% and 40%, estimated glomerular filtration rate (eGFR), changes in symptoms and quality-of-life scores, and adverse events. Results: The changes of the natural log-UACR during the 24 weeks compared with baseline in the KLX group were better than those in the control group (LS mean ± standard error, -0.26 ± 0.10 vs. 0.01 ± 0.09, p = 0.0292). The incidence of a sustained increase in the UACR of at least 30% and 40% was found to be significantly lower in the KLX group (OR, 0.26; 95% confidence interval [CI], 0.09-0.75; OR, 0.29; 95% CI, 0.10-0.82). Changes in symptoms and quality-of-life scores in the KLX group were better than those in the control group. There was no statistically significant difference in eGFR or the incidence of adverse events between the groups. Conclusions: Overall, these results suggest that KLX capsules combined with irbesartan can reduce microalbuminuria, relieve the symptoms, and improve the quality of life for patients with type 2 early DKD compared with the use of irbesartan alone. Trial registration: Chinese Clinical Trial Registry, registration number: ChiCTR2100052764.

Analysis of clinical evidence on traditional Chinese medicine for the treatment of diabetic nephropathy: a comprehensive review with evidence mapping.

Objective: This study aims to map evidence from Randomized Controlled Trials (RCTs) and systematic reviews/Meta-analyses concerning the treatment of Diabetic Nephropathy (DN) with Traditional Chinese Medicine (TCM), understand the distribution of evidence in this field, and summarize the efficacy and existing problems of TCM in treating DN. The intention is to provide evidence-based data for TCM in preventing and treating DN and to offer a reference for defining future research directions. Methods: Comprehensive searches of major databases were performed, spanning from January 2016 to May 2023, to include clinical RCTs and systematic reviews/Meta-analyses of TCM in treating DN. The analysis encompasses the publishing trend of clinical studies, the staging of research subjects, TCM syndrome differentiation, study scale, intervention plans, and outcome indicators. Methodological quality of systematic reviews was evaluated using the AMSTAR (Assessment of Multiple Systematic Reviews) checklist, and evidence distribution characteristics were analyzed using a combination of text and charts. Results: A total of 1926 RCTs and 110 systematic reviews/Meta-analyses were included. The majority of studies focused on stage III DN, with Qi-Yin deficiency being the predominant syndrome type, and sample sizes most commonly ranging from 60 to 100. The TCM intervention durations were primarily between 12-24 weeks. Therapeutic measures mainly consisted of Chinese herbal decoctions and patented Chinese medicines, with a substantial focus on clinical efficacy rate, TCM symptomatology, and renal function indicators, while attention to quality of life, dosage of Western medicine, and disease progression was inadequate. Systematic reviews mostly scored between 5 and 8 on the AMSTAR scale, and evidence from 94 studies indicated potential positive effects. Conclusion: DN represents a significant health challenge, particularly for the elderly, with TCM showing promise in symptom alleviation and renal protection. Yet, the field is marred by research inconsistencies and methodological shortcomings. Future investigations should prioritize the development of standardized outcome sets tailored to DN, carefully select evaluation indicators that reflect TCM's unique intervention strategies, and aim to improve the robustness of clinical evidence. Emphasizing TCM's foundational theories while incorporating advanced scientific technologies will be essential for innovating research methodologies and uncovering the mechanisms underlying TCM's efficacy in DN management.

Evidence mapping of traditional Chinese medicine in diabetic peripheral neuropathy treatment.

Objective: Diabetic peripheral neuropathy (DPN) stands as a crucial complication of diabetes, significantly affecting patients' quality of life. This study aims to elucidate the evidence distribution from clinical randomized controlled trials (RCTs) on DPN treatment with traditional Chinese medicine (TCM) through evidence mapping. Methods: A comprehensive search was conducted from January 2017 to October 2022 in databases such as Wanfang (China Online Journals), CNKI (China National Knowledge Infrastructure), VIP (China Science and Technology Journal Database), SinoMed (Chinese Biomedical Literature Database), PubMed, Web of Science, and Cochrane Library. Literature related to the treatment of DPN with TCM was selected. From the 1,229 RCTs identified over the past 6 years, relevant data were extracted. The evidence mapping approach was utilized, and trends in publications, study scales, intervention types, and evaluation indicators were analyzed using descriptive text combined with tables and bubble charts. Results: Research on the treatment of DPN with TCM is extensive. The publication trend remains relatively stable with predominantly smaller sample sizes. The main treatments encompass oral Chinese medicine and traditional external treatments. The most common evaluation indicators are neurophysiological, efficiency rate, symptom signs, neuropathy scores, and traditional Chinese symptoms, with less focus on psychological status and the ankle-brachial index (ABI). Conclusion: Shedding light on contemporary research, this study explores the current RCTs evaluating TCM's efficacy in treating DPN. The findings not only highlight the potential role of TCM in addressing diabetic complications but also underscore areas that could benefit from refined research approaches, expanded intervention methods, and broader assessment criteria. Our observations aim to inform and inspire future research directions and clinical practices concerning TCM's role in managing diabetes-associated complications.

Recent updates on 1,2,3-triazole-containing hybrids with in vivo therapeutic potential against cancers: A mini-review.

1,2,3-Triazole moiety which is usually constructed by highly versatile, efficacious and selective copper-catalyzed azide-alkyne cycloaddition not only can act as a linker to connect different pharmacophores, but also is a useful pharmacophore with diverse biological properties. 1,2,3-Triazoles are readily interact with diverse enzymes and receptors in cancer cells through non-covalent interactions and can inhibit cancer cell proliferation, arrest cell cycle and induce apoptosis. In particular, 1,2,3-triazole-containing hybrids have the potential to exert dual or multiple anticancer mechanisms of action, representing useful scaffolds in expediting development of novel anticancer agents. The current review summarizes the in vivo anticancer efficacy and mechanisms of action of 1,2,3-triazole-containing hybrids reported in the last decade to continuously open up a map for the remarkable exploration of more effective candidates.

A dynamic study of the postoperative management of thyroid cancer from 2003 to 2022: a bibliometric analysis.

Background: Over the past 20 years, the global incidence of thyroid cancer has continued to increase. The volume of literature on the postoperative management of thyroid cancer comprises 1,040 articles, from 64 countries, with 1,400 journals publishing the relevant literature, and several guidelines on the treatment of thyroid cancer. This study used bibliometric methods to identify research hotspots and explore future directions in this field. Methods: We comprehensively searched the Science Citation Index Expanded (SCI-E) database of the Web of Science Core Collection (WOSCC) for articles published from 2003 to 2022 on the postoperative management of thyroid cancer. Using CiteSpace 6.1.R6 and Microsoft Office Excel 2010, we evaluated and visualized the search results. Using R Studio, we generated a network of spatial geographic distribution maps and cooperative network. Results: A total of 1,040 publications were included in the study. The results revealed an overall upward trend in the number of publications and citations over the past 20 years. The United States of America (USA) had the largest number of publications and the highest centrality (n=282, centrality =0.28). Johns Hopkins University had highest centrality (centrality =0.15) and was the academic center of the field. Thyroid was the journal with the highest number of citations (n=826), and the American Journal of Surgical Pathology was the journal with the highest centrality (centrality =0.08). The top 10 citations in the literature were mainly guidelines and consensus statements on the management of thyroid cancer. A keyword-based clustering analysis revealed the prominence of clusters of keywords, such as follow-up, recurrent laryngeal nerve, and medullary thyroid carcinoma (MTC). A keyword burst detection analysis showed that the term papillary had the highest burst intensity (strength =8.02), while management guidelines, association guidelines, active surveillance (AS), microcarcinoma, and differentiated thyroid cancer were the current burst words. Conclusions: Over the past two decades, the number of relevant publications in the postoperative management of thyroid cancer field has continued to grow. Among the many research directions, follow-up, recurrent laryngeal nerve, and MTC are research hotspots. Future research is likely to revolve around guidelines and consensus statements on the management of thyroid cancer, AS, and microcarcinoma in differentiated thyroid cancer.

Knowledge domain and emerging trends in beta-cell research: A bibliometric and knowledge-map analysis.

Background: Up to now, the physiology, pathology, and recovery of beta-cells have been intensively studied and made great progress, and these are of major significance for the treatment of related diseases. Nevertheless, a comprehensive and objective report on the status of beta-cell research is lacking. Therefore, this study aims to conduct a bibliometric analysis to quantify and identify the current status and trending issues in beta-cell research. Methods: The articles and reviews related to beta-cell were obtained from the Web of Science Core Collection on August 31, 2022. Two scientometric software (CiteSpace 6.1.R3 and VOSviewer 1.6.18) were used to perform bibliometric and knowledge-map analysis. Results: A total of 4098 papers were published in 810 academic journals in 2938 institutions from 83 countries/regions. The number of beta-cell-related publications was increasing steadily. The United States was the most productive country, while Universite libre de Bruxelles, University of Toronto and University of Geneva were the most active institutions. Diabetes published the most beta-cell studies and received the largest number of co-citations. Decio I Eizirik published the most papers and had the most co-citations. Twelve references on reviews and mechanisms were regarded as the knowledge base. Four major aspects of beta-cell research included the pathological mechanism of beta-cell failure, the recovery of beta cells, the risk factor related to beta cells, and the physiology of beta cells. Endoplasmic reticulum stress and oxidative stress have been core elements throughout the research in this field. In addition, beta-cell dedifferentiation, inflammation, autophagy, miRNA, and lncRNA are hot topics nowadays. Additionally, stem cell replacement therapies might be the alternative way to reverse beta-cell failure. Restoring beta-cell mass and function will remain a research goal in the future. Conclusion: This study provided a comprehensive overview of beta-cell research through bibliometric and visual methods. The information would provide helpful references for scholars focusing on beta cells.

Comparative study of disease progression for heart failure with different etiologies via time-ordered network analysis.

OBJECTIVES: Heart failure (HF), the primary end-stage manifestation of multiple cardiovascular diseases, has become a global epidemic with high morbidity and mortality. However, the mechanisms underlying the pathogenesis of HF with different etiologies have yet to be fully elucidated. METHODS: In this study, we developed a novel method to determine the dysregulated lncRNA-mRNA regulation pairs (LMRPs) in the different causes that lead to HF. Time-ordered dysregulated lncRNA-mRNA regulation networks were constructed for comparing the HF progression initiated from different causes. Additionally, the random forest and support vector machine classification algorithm were applied to identify HF-related diagnostic biomarkers. RESULTS: Biological functional analysis indicated that similar functions were detected at the late stage across different causes of HF, whereas different characteristics were revealed during disease progression. Specifically, the disturbance of myocardial energy metabolism might be a cause of dilated cardiomyopathy (DCM) and peripartum cardiomyopathy (PPCM), while immune response appeared earlier in hypertrophic cardiomyopathy (HCM). Inflammatory response during HCM and PPCM progression might be mediated by complement system, whereas ischemic cardiomyopathy (ICM) might be induced by cytokines. Finally, we identified several panels of diagnostic biomarkers for distinguishing HF patients of different etiologies from non-heart failure (NF) controls. CONCLUSIONS: This study revealed distinct functional characteristics during the progression of HF from different causes and facilitated the discovery of candidate diagnostic biomarkers for HF.

[Clinical effect of cortical incision with rapid maxillary expansion to assist orthodontic-orthognathic treatment of skeletal Class â ¢ malocclusion].

PURPOSE: To investigate the clinical effect of rapid maxillary expansion with cortical osteotomy combined with orthodontic- orthognathic treatment for skeletal Class Ⅲ malocclusion. METHODS: A total of 84 patients with skeletal Class Ⅲ malocclusion admitted to Jining Dental Hospital from March 2018 to May 2020 were randomly divided into experimental group and control group, with 42 cases in each group. The control group was treated with orthodontic-orthognathic treatment, while the experimental group was treated with orthodontic-orthognathic treatment with rapid maxillary arch expansion by cortical incision. The time of closing gap, alignment time, maxillary first molar and maxillary central incisor tooth movement distance in the sagittal direction were compared between the two groups. Before treatment and 4 weeks after treatment, the vertical distance from the end of the upper central incisor edge to the horizontal plane(U1I-HP), the distance from the apex of the upper central incisor to the coronal plane(U1I-CP), the vertical distance from the edge of the upper pressure groove to the coronal plane(Sd-CP), the vertical distance from the upper alveolar seat point to the horizontal plane(A-HP), the vertical distance from the point of the upper lip to the coronal plane(Ls-CP), and the vertical distance from the inferior point of nose to coronal plane(Sn-CP) were measured, and the relevant changes were calculated. During the treatment period, the complications of the two groups were compared. SPSS 20.0 software package was used for statistical analysis of the data. RESULTS: There was no significant difference in alignment time, A-HP change, Sn-CP change, maxillary first molar movement distance and maxillary central incisor movement distance between the two groups (P＞0.05). The closing interval in the experimental group was significantly shorter than that of the control group (P＜0.05). The changes of U1I-HP, U1I-CP, Sd-CP, and Ls-CP in the experimental group were significantly higher than those in the control group (P＜0.05). There was no significant difference in the incidence of complications between the two groups during treatment (P＞0.05). CONCLUSIONS: Rapid maxillary expansion of cortical incision assisted orthodontic-orthognathic treatment of skeletal Class Ⅲ malocclusion patients can shorten the closing gap time and improve the treatment effect, which has no obvious influence on the sagittal direction of the teeth.

Efficacy and Safety of Mulberry Twig Alkaloids Tablet for Treatment of Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Multicenter Clinical Study.

OBJECTIVE: To assess the efficacy and safety of mulberry twig alkaloids (Sangzhi alkaloids, SZ-A) for treatment of type 2 diabetes in a randomized, double-blind, placebo-controlled multicenter clinical trial. METHODS: A total of 200 patients were randomized to receive SZ-A (n=100) or placebo (n=100) for 16 weeks. The data analysis system for electronic data capture clinical trial central randomization system was used for randomization and dispensing of drugs. The primary outcome was the change in glycosylated hemoglobin (HbA1c) level. The secondary outcome included the proportions of cases with HbA1c <7.0% and HbA1c <6.5%, fasting blood glucose (FBG), postprandial blood glucose (PBG), area under curve for the PBG (AUC0-2h), body weight, and body mass index (BMI). Adverse events (AEs), severe adverse events (SAEs), treatment-related adverse events (TAEs), gastrointestinal disorders (GDs), blood pressure, routine blood tests, and liver and kidney function were monitored. RESULTS: Compared with baseline, the change of HbA1c at week 16 was -0.80% (95% CI: -0.98% to -0.62%) and -0.09% (95% CI: -0.27% to 0.09%) in SZ-A group and placebo group, respectively. The proportion of patients with HbA1c <7% and <6.5% was higher in the SZ-A group than in the placebo group (46.8% vs. 21.6% and 29.9% vs. 10.8%). The observed values and changes in FBG, 1 h-PBG, 2 h-PBG, and AUC0-2h differed significantly between groups (P<0.001), but differences were not significant in body weight and BMI (P>0.05). The incidence rates of AEs, TAEs, and GDs differed significantly between groups (P=0.010, P=0.005, and P=0.006, respectively), whereas the incidence rates of SAEs showed no significant differences between groups (P=1.000). CONCLUSION: SZ-A are effective and safe for treatment of type 2 diabetes. The protocol was registered in http://www.chictr.org.cn/showproj.aspx?proj=60117 (ChiCTR2000038550).

Time-ordered dysregulated ceRNA networks reveal disease progression and diagnostic biomarkers in ischemic and dilated cardiomyopathy.

Ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) are the two main causes of heart failure (HF). Despite similar clinical characteristics and common "HF pathways", ICM and DCM are expected to have different personalized treatment strategies. The underlying mechanisms of ICM and DCM have yet to be fully elucidated. The present study developed a novel computational method for identifying dysregulated long noncoding RNA (lncRNA)-microRNA (miRNA)-mRNA competing endogenous RNA (ceRNA) triplets. Time-ordered dysregulated ceRNA networks were subsequently constructed to reveal the possible disease progression of ICM and DCM based on the method. Biological functional analysis indicated that ICM and DCM had similar features during myocardial remodeling, whereas their characteristics differed during progression. Specifically, disturbance of myocardial energy metabolism may be the main characteristic during DCM progression, whereas early inflammation and response to oxygen are the characteristics that may be specific to ICM. In addition, several panels of diagnostic biomarkers for differentiating non-heart failure (NF) and ICM (NF-ICM), NF-DCM, and ICM-DCM were identified. Our study reveals biological differences during ICM and DCM progression and provides potential diagnostic biomarkers for ICM and DCM.

Efficacy and Safety of Mulberry Twig Alkaloids Tablet for the Treatment of Type 2 Diabetes: A Multicenter, Randomized, Double-Blind, Double-Dummy, and Parallel Controlled Clinical Trial.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of mulberry twig alkaloids (Sangzhi alkaloids [SZ-A]) in the treatment of type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: This was a multicenter, randomized, double-blind, double-dummy, and parallel controlled noninferiority clinical trial that was conducted for 24 weeks. A total of 600 patients were randomly allocated to the SZ-A group (n = 360) or acarbose group (n = 240). The primary efficacy end point was the change of glycosylated hemoglobin (HbA1c) compared with baseline. In addition, adverse events (AEs), severe AEs (SAEs), treatment-related AEs (TAEs), and gastrointestinal disorders (GDs) were monitored. RESULTS: After treatment for 24 weeks, the change in HbA1c was -0.93% (95% CI -1.03 to -0.83) (-10.2 mmol/mol [-11.3 to -9.1]) and -0.87% (-0.99 to -0.76) (-9.5 mmol/mol [-10.8 to -8.3]) in the SZ-A and acarbose groups, respectively, and the least squares mean difference was -0.05% (95% CI -0.18 to 0.07) (-0.5 mmol/mol [-2.0 to 0.8]) between the two groups, with no significant difference on the basis of covariance analysis (P > 0.05). The incidence of TAEs and GDs was significantly lower in the SZ-A group than the acarbose group (P < 0.01), but no differences for AEs or SAEs between the two groups were observed (P > 0.05). CONCLUSIONS: SZ-A exhibited equivalent hypoglycemic effects to acarbose in patients with T2D. Nevertheless, the incidence of TAEs and GDs was lower following SZ-A treatment than acarbose treatment, suggesting good safety.

[Retrospective study on Chinese medicine syndrome patterns and their associated factors in patients with type 2 diabetic nephropathy stage III].

OBJECTIVE: To explore the relationship between Chinese medicine syndrome patterns (CMSP) and their associated factors in patients with type 2 diabetic nephropathy stage III (DN2-3). METHODS: Retrospective analysis was conducted on 209 patients with type 2 diabetes mellitus (T2DM). The patients were allocated into two groups, the DN2-3 group and the control group. Some related clinical materials and laboratory indexes, including age, course of disease, body mass index (BMI), glycosylated hemoglobin A1c (HbA1c), systolic blood pressure (SBP), diastolic blood pressure (DBP), blood levels of total cholesterol (TC), triglyceride (TG), high and low density lipoprotein (HDL and LDL), serum creatinine (Scr) and microalbuminuria (MALB) as well as their CMSP (both the essential syndrome and the superficial syndrome) in the DN2-3 group were collected and compared. RESULTS: Significant differences were found between the DN2-3 group and the control group in aspects of course of disease (months, 107.74 +/- 96.19 vs. 82.03 +/- 79.10), BMI (kg/m2, 26.25 +/- 4.02 vs. 24.95 +/- 3.56) and Scr level (mmoL/L, 71.93 +/- 24.24 vs. 65.91 +/- 13.70, P < 0.05). The qi-yin deficiency SP (38 cases, 36.19%), and the blood stasis (51 cases, 48.58%) presented as the dominant essential and superficial CM-SP respectively in DN2-3 patients, holding the highest proportion. Analysis on the relationship of associated indices among patients with different CMSP showed statistical differences presented in level of MALB, i.e. which in pi-shen qi-deficiency SP (128.77 +/- 103.59 mg/24 h) was higher than in yin-deficiency dryness-fire SP and qi-yin deficiency SP (88.43 +/- 68.93 mg/24h and 82.60 +/- 55.22 mg/24 h, P < 0.05); it also presented in HbA1c (%) and TG levels(mmol/L), those in stasis SP were 10.73 +/- 2.71 and 2.29 +/- 1.58 ), in dampness SP were 8.80 +/- 2.19% and 4.37 +/- 5.92, and in stasis-phlegm SP were 8.83 +/- 2.09 and 2.40 +/- 2.18 (all P < 0.05). CONCLUSIONS: The risk factors for occurrence of DN2-3 may be the course of disease, BMI and Scr. Qi-yin deficiency with blood-stasis is the most commonly encountered syndrome in patients with DN2-3. Relations of MALB with Pi-Shen qi-deficiency pattern; HbA1c with blood-stasis pattern, and TG with dampness syndrome are distinctly exhibited in them.

Systematic analysis of lncRNA and microRNA dynamic features reveals diagnostic and prognostic biomarkers of myocardial infarction.

Analyses of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) implicated in myocardial infarction (MI) have increased our understanding of gene regulatory mechanisms in MI. However, it is not known how their expression fluctuates over the different stages of MI progression. In this study, we used time-series gene expression data to examine global lncRNA and miRNA expression patterns during the acute phase of MI and at three different time points thereafter. We observed that the largest expression peak for mRNAs, lncRNAs, and miRNAs occurred during the acute phase of MI and involved mainly protein-coding, rather than non-coding RNAs. Functional analysis indicated that the lncRNAs and miRNAs most sensitive to MI and most unstable during MI progression were usually related to fewer biological functions. Additionally, we developed a novel computational method for identifying dysregulated competing endogenous lncRNA-miRNA-mRNA triplets (LmiRM-CTs) during MI onset and progression. As a result, a new panel of candidate diagnostic biomarkers defined by seven lncRNAs was suggested to have high classification performance for patients with or without MI, and a new panel of prognostic biomarkers defined by two lncRNAs evidenced high discriminatory capability for MI patients who developed heart failure from those who did not.

Recent Development of Coumarin Derivatives as Potential Antiplasmodial and Antimalarial Agents.

Malaria still remains one of the leading deadliest diseases throughout the world, leading to around 1 million deaths annually. The emergence and spread of growing resistance to the firstline antimalarials are an alarming the serious problem in malaria control, demanding the need for new drugs more potent than earlier with improved Absorption, Distribution, Metabolism, and Excretion (ADME) profiles. Coumarins, which exhibited various biological properties, also displayed potential in vitro antiplasmodial and in vivo antimalarial activities. Moreover, many of coumarin derivatives have already been used in clinical practice for the treatment of several diseases. Therefore, coumarin derivatives play a pivotal role in medicinal chemistry, also making them promising candidates for the treatment of malaria. This review aims to summarize the recent advances made towards the development of coumarin-containing derivatives as antiplasmodial and antimalarial agents and their structure-activity relationship is also discussed.