Mechanism of Gegen Qinlian Decoction in Treating Type 2 Diabetes Mellitus Complicated with NAFLD Based on Network Pharmacology

[Objectives]To explore the mechanism of Gegen Qinlian Decoction in treating type 2 diabetes mellitus(T2DM)complicated with non-alcoholic fatty liver disease(NAFLD)by analyzing the effective components of Gegen Qinlian Decoction.[Methods]TCMSP database was used to analyze the active components of Gegen Qinlian Decoction,and pubchem and Swiss ADME databases were also used to predict drug targets,extract T2DM complicated with NAFLD targets from OMIM and Genecards databases.Venny plot was drawn to obtain intersection targets,and finally Cytoscape was used to make core target maps and drug-target-disease network maps.Using DAVID and Metascape database to analyze the intersection targets,the gene ontology information of Go and KEGG was obtained.Microbial informatics technology was used to visualize GO,and Cytoscape was used to make drug-target-disease network map-enrichment pathway map.[Results]The network pharmacological analysis showed that Gegen Qinlian Decoction acted on the key targets of type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease,such as ALB and ALT1,through many components,and achieved the purpose of treating this disease.The chemical constituents of the drug include formononetin,5-hydroxyisomucronulatol-2,5-2-O-glucoside,cholesteryl laurate,isoliquiritigenin,etc.[Conclusions]This study provides a new idea and theoretical support for future drug research and clinical practice.

Obesity and the risk of cardiovascular disease and diabetes mellitus

The increasing prevalence of obesity worldwide has many experts concerned about the worsening health of a large proportion of the population. It is well recognized that obesity is associated with a higher mortality, an increased risk of hypertension and hyperlipidemia, cardiovascular disease, diabetes mellitus, osteoarthritis, gall bladder disease and possibly some cancers. Currently it is estimated that over two thirds of adults in the United States are overweight and nearly one third are clinically obese.1 Of special concern is the rapid increase in obesity among children. Other countries both developed and developing are experiencing similar trends.……

Clinical Characteristics and Coronary Angiographic Findings in Patients with Coronary Heart Disease and Type 2 Diabetes Mellitus

Objectives To study clini- cal and coronary angiographic findings in patients with both coronary heart diseases (CHD) and type 2 diabe- tes mellitus (T2DM). Methods 215 patients with CHD confirmed by coronary angiography were involved in this study. The patients were divided into two groups: 74 CHD patients with T2DM (mean age 64.7 ± 8.2 years, male/female 47/27), and 141 CHD pa- tients without T2DM ( mean age 66. 2 ±9. 2 years, male/female 100/41 ). The clinical features and the data from selective coronary angiographies were com- pared between type 2 diabetic and non - diabetic CHD patients. Results Compared to non - diabetic CHD patients, the patients with both CHD and T2DM suf- fered more from acute myocardial infarction, silent is- chemia and severe arrhythmias ( P < 0. 01, P < 0. 05 ) , and had higher serum triglycerides and apo - lipoprotein B, along with increased serum uric acid (P < 0. 01, P < 0.05), increased left ventricular end diastolic diameter ( P < 0. 01 ) , and decreased left ventricular ejection fraction ( P < 0. 001 ). Compared to non - diabetic CHD patients, the patients with both CHD and T2DM suffered more from triple vessel disease (P < 0. 01) , severe coronary artery stenosis, complete occlusions and diffuse lesions ( P < 0. 001). Conclusions Se- vere clinical manifestation, left ventricular dysfunction, diffuse or complicated lesions of coronary arteries weremore common in patients with both CHD and T2DM, it suggests that the type 2 diabetic CHD patients have poor prognosis.

Modified upper abdominal cluster transplantation in patients with end-stage liver diseases associated with insulin dependent type 2 diabetes mellitus

Objective Modified upper abdominal cluster transplantation ( MCT) ,which was inspired by classical cluster transplant technique,has been proven more effective and feasible in the treatment of patients with end stage liver diseases associated with insulin - dependent

A Retrospective Study of Branch Atheromatous Disease： Analyses of Risk Factors and Prognosis

The theory of branch atheromatous disease（BAD） has been commonly underused in clinical practice and research since it was proposed in 1989. In this study, we sought to explore clinical characteristics of its substypes and biomarkers for prognosis of BAD. A total of 176 consecutive patients with BAD were classified into two groups： paramedianpontine artery group（PPA group, n=70） and lenticulostriate artery group（LSA group, n=106）. Bivariate analyses were used to explore the relationship between white matter hyperintensities（WMHs）, National Institutes of Health Stroke Scale（NIHSS） scores and prognosis evaluated by the modified Rank Scale（m RS） at 6th month after stroke. The differences in prevalence of diabetes mellitus and a history of ischemic heart disease were statistically significant between PPA group and LSA group（χ~2=8.255, P=0.004; χ~2=13.402, P〈0.001）. The bivariate analyses demonstrated a positive correlation between NIHSS and poor prognosis in patients with BAD and in the two subtype groups, and a positive correlation between WMHs and poor prognosis in the PPA group. It is concluded that a significantly higher prevalence of diabetes mellitus and a history of ischemic heart disease exist in the PPA group than in the LSA group. In addition, high grades of NIHSS scores imply poor prognosis in patients with BAD and in the two subtype groups. Moreover, WMHs are a positive predictor for poor prognosis in patients in the PPA group.

Impact of estimated HDL particle size via the ratio of HDL-C and apoprotein A-I on short-term prognosis of diabetic patients with stable coronary artery disease

BackgroundRevascularization and statin therapy are routinely used in the management of stable coronary artery disease. However, it is unclear whether the estimated high-density lipoprotein （HDL） particle size （eHDL-S）, the ratio of HDL cholesterol （HDL-C） to apoprotein A-I （apoA-I）, is associated with the clinical outcomes of diabetic patients with stablecoronary artery disease （CAD）.MethodsWe per-formed a prospective cohort study of 328 patients diagnosed with stable CAD by coronary angiography. Patients were followed up for a mean duration of 12 months. The patients were divided into three groups by the tertiles of eHDL-S： low eHDL-S （〈 0.71,n= 118）; interme-diate eHDL-S （0.71-0.79,n= 111）; and high eHDL-S （〉 0.79,n= 99）. The associations between the baseline eHDL-S and short-term out-comes were evaluated using the Kaplan-Meier method and Cox proportional regression.Results The low eHDL-S group had higher trig-lyceride, hemoglobin A1c, uric acid, and leukocyte count than the other groups. During the follow-up period, 47/328 patients experienced a pre-specified outcome. According to the Kaplan-Meier analysis, the incidence of pre-specified outcomes was lower in the high eHDL-S group （P = 0.04）. However, eHDL-S was not independently associated with adverse outcomes in Cox proportional hazards regression （haz-ard ratio （HR）： 0.23, 95% confidence interval （95% CI）： 0.01-11.24,P = 0.493）.ConclusionAlthough the eHDL-S was associated with inflammatory biomarkers, it was not independently associated with the short-term prognosis of diabetic patients with stable CAD in the era of revascularization and potent statin therapy.

Genetic variability in adapter proteins with APPL1/2 is associated with the risk of coronary artery disease in type 2 diabetes mellitus in Chinese Han population

Background Adaptor proteins containing PH domain, PTB domain, and leucine zipper motif 1 and 2 （APPL1/2） play a key role in cell proliferation in many tissues. APPL1 or APPL2 as an adaptor for adiponectin receptors mediates the signaling pathway of adiponectin which acts as an anti-atherosclerotic adipokine. This study aimed to investigate whether genetic variations in the APPL 1/2 genes affect the risk of coronary artery disease （CAD） in Chinese patients with type 2 diabetes mellitus （T2DM）. Methods Seven haplotype-tagging single nucleotide polymorphisms （tag-SNPs） were selected from CHB HapMap database （Phase II） and total 203 CAD-positive cases and 106 CAD-negative controls with T2DM were genotyped for the 7 tag-SNPs by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） assay. Results The minor allele G of rs4640525 at APPL1 locus was protective from CAD in patients with T2DM, with the carriers of genotype CC at higher risk of CAD compared with non-carriers （OR=2.830, 95% Cl 1.285-6.230, P=0.010; OR＇=4.992, 95% C1=1.758-14.173, P＇0.003, after adjustment for the other known CAD risk factors）; the homozygotes of AA at rs11112412 in APPL2 gene had higher risk of CAD compared with those of GG （adjusted OFt=5.697, 95% Cl 1.006-32.257, P=0.049）. Conclusion Genetic variation（s） in APPL 1/2 may be associated with CAD risk in T2DM in Chinese population.

Polymorphism on chromosome 9p21.3 contributes to early-onset and severity of coronary artery disease in non-diabetic and type 2 diabetic patients

Background Susceptibility to coronary artery disease （CAD） and diabetes is encoded by distinct, tightly-linked single nucleotide polymorphisms on chromosome 9p21. This study aimed to examine the association of variant rs1333049 on chromosome 9p21.3 with early-onset and severity of CAD in Chinese patients with and without type 2 diabetes, and to determine the possible impact of rs1333049 on glucose metabolism and inflammation pathways. Methods Genotyping of variant rs1333049 on chromosome 9p21.3 was performed in 2387 patients with and without diabetes who were undergoing coronary angiography to evaluate suspected or established CAD. Serum levels of glucose, glycosylated hemoglobin Alc （HbAlo）, insulin, high-sensitivity C-reactive protein, tumor necrosis factor-a, and interleukin-6 were also measured, and compared with each patient＇s genotype. Results The homozygous CC genotype of rs1333049 was significantly associated with CAD in diabetic （OR： 1.270, P=-0.044） and non-diabetic （OR： 1.369, P=0.011） patients after adjusting for traditional risk factors. There was an association between CC genotype and number of diseased vessels in diabetics （P=0.019）, but not in non-diabetics （P=0.126）. Among diabetic patients, CC genotype carriers had an increased risk of early-onset CAD （OR：. 2.367, ,~=-0.008） and greater cumulative atherosclerotic burden compared with non-CC genotype carriers （Gensini score： 31.80＋17.20 vs. 23.09＋_21.63, P=-0.039）. No significant differences were observed between genotypes of rs1333049 in serum levels of glucose, insulin, HbAlc, or inflammatory cytokines for diabetic or non-diabetic patients with CAD. Conclusions This study demonstrated a significant association of rs1333049 polymorphism on chromosome 9p21.3 with CAD in Chinese diabetic and non-diabetic patients. The homozygous CC genotype of rs1333049 confers a magnified risk of early-onset and more severe CAD in diabetic patients through a novel biological pathway unrelated to glucose metabolism or inflammation.

IKK inhibition prevents PM_(2.5)-exacerbated cardiac injury in mice with type 2 diabetes

Epidemiological studies have found that individuals with diabetes mellitus（DM） display an increased susceptibility for adverse cardiovascular outcomes when exposed to air pollution.This study was conducted to explore the potential mechanism linking ambient fine particles（PM2.5） and heart injury in a Type 2 DM（T2DM） animal model. The KKay mouse, an animal model of T2DM, was exposed to concentrated ambient PM2.5 or filtered air for 8 weeks via a versatile aerosol exposure and concentrator system. Simultaneously, an inhibitor of IκB kinase-2（IKK-a）（IMD-0354）, which is a blocker of nuclear factor κB（NF-κB）nuclear translocation, was administrated by intracerebroventricular injection（ICV） to regulate the NF-êB pathway. The results showed that ambient PM2.5 induced the increase of, NF-êB, cyclooxygenase-2（COX-2） and mitogen activated protein kinase（MAPK） expression in cardiac tissue, and that IMD-0354 could alleviate the inflammatory injury. The results suggested that the NF-êB pathway plays an important role in mediating the PM2.5-induced cardiovascular injury in the T2DM model. Inhibiting NFκB may be a therapeutic option in air-pollution-exacerbated cardiovascular injury in diabetes mellitus.

Simultaneous pancreas-kidney transplantation in a single center： 10-year retrospective analysis

Background Simultaneous pancreas-kidney transplantation （SPKT） is the best treatment option for diabetic patients with advanced chronic renal failure. The current study aimed to analyze the surgical indications, treatments and prognosis of SPKT.Methods We retrospectively analyzed 40 cases of SPKT performed between December 1999 and January 2010 in our center, including the survival rate, complications and the reasons of reoperation.Results Of all the 40 SPKT cases, the one-year survival rates of the recipients, kidney and pancreas transplant graft were 97.6%, 97.6% and 92.7%, while 97.6%, 91.1%, 92.7% at 3 years and 83.6%, 78.0%, 79.4% at 5 years, respectively. After SPKT, 10 patients need reoperation because of surgical complications （14 operations）. The reoperation rate was 25%, including 2 patients （4 operations） with hematuria, 4 patients with abdominal hemorrhage, 2 patients （3 operations） with abdominal infection, 1 patient with pancreatic venous thrombosis, 1 patient with anastomotic leakage, and 1 patient with fistula.Conclusion Although SPKT provides a successful and effective treatment for diabetics with end-stage renal disease, how to reduce the complications of this treatment still need further effort.