"Omics" and bioinformatics have brought new ideas to the study of traditional Chinese medicine. This study used metabonomics and network pharmacology to investigate the pharmacodynamic basis and regulation of Qishen Yiqi dropping pill (QDP) improving cardiac energy metabolism in rats with heart failure (HF). ¹H NMR metabonomics analysis showed that eight metabolites, including carnitine, glutamine, creatine, proline, homocitrulline, lactic acid, taurine and alanine appeared significant callback after QDP treatment for HF. The results indicate that QDP regulates the metabolism of carbohydrate, lipid, ATP and protein. The animal experiment was conducted in accordance with the regulations of the Ethics Committee for Experimental Animal Management and Animal Welfare of Institute of Materia Medica, Chinese Academy of Medical Sciences. A "drug-component-target-disease" network was established using network pharmacology, and the "component-target" sub-network related to the above energy metabolism processes was extracted by combining metabonomics results. Results revealed 79 chemical compounds and 47 potential targets of QDP involved in the regulation of energy metabolism, and identified key chemical components including ursolic acid, notoginsenoside G, ginsenoside-Rh1, and core targets such as INS, PPARG, and AKT1. The results also demonstrated the complex multi-target and multi-component relationship between QDP and HF from the perspective of energy metabolism. The molecular docking technique verified a strong interaction between some targets and chemical compounds, with affinities less than -5 kcal·mol^-1. The results of this study provide useful information for the clinical application, development, and utilization of QDP.

Studies have found that metformin is not only the preferred drug for lowering blood sugar, but also shows lipid-lowering and weight-loss effects. The purpose of this study was to use a hyperlipidemia hamster model to investigate the lipid-lowering effect of metformin and its effect on important metabolic pathways in lipid metabolism disorders. Fifty golden hamsters were divided into a control group, a model group, metformin high- and low-dose groups, and a simvastatin group. A high-fat diet was fed for 1 week to create the model, and then drug was administered for 11 weeks with the high-fat diet. Serum was taken for measurement of blood lipid and blood glucose at 2, 6, and 9 weeks after administration, and at weeks 3, 5, and 9 feces and urine were collected for ¹H NMR metabolomics tests. After 11 weeks of intravenous injection of [U-¹³C₆] glucose, serum was collected for a ¹³C NMR metabolic flux test. The results showed that the administration of metformin can significantly reduce blood lipids and glucose levels and can significantly affect metabolic pathways such as sugar metabolism, lipid metabolism, ketone metabolism, amino acid metabolism, and intestinal flora metabolism. The results of the metabolic flux analysis showed that the high-fat diet reduced the metabolism of tricarboxylic acids by 37.48%. After administration of low and high doses of metformin the metabolism of tricarboxylic acid increased by 98.14% and 143.10%, respectively. After administration of simvastatin tricarboxylic acid metabolism increased by 33.18%. The results indicate that metformin has a significant effect on promoting energy metabolism. This study used a combination of metabolomics and metabolic flow to explore the effect of metformin on lipid metabolism disorders and quantifies changes in the key pathway of energy metabolism-the tricarboxylic acid cycle. This study provides useful information for the study of the efficacy and mechanism of metformin, as well as a practical technical method for the screening of lipid-lowering drugs based on a hamster model.

BACKGROUNDThe accurate and comprehensive assessment of glycemic control in patients with diabetes is important for optimizing glycemic management and for formulating personalized diabetic treatment schemes. This study aimed to analyze the correlation between 1,5-anhydroglucitol (1,5-AG) and glycemic excursions in type 2 diabetic patients.

METHODSSeventy-one outpatients with type 2 diabetes mellitus were randomly recruited from Chinese People's Liberation Army General Hospital. Using a continuous glucose monitoring system (CGMS), these patients' blood glucose levels were monitored for three consecutive days to obtain mean blood glucose (MBG) data. Intraday glycemic excursions were evaluated using the mean amplitude of glycemic excursions (MAGE), the largest amplitude of glycemic excursions (LAGE), standard deviation of blood glucose (SDBG) and the M-value. Interday glycemic excursion was assessed by absolute mean of daily difference (MODD). Postprandial glycemic fluctuations were evaluated using postprandial glucose excursions (PPGE) and postprandial incremental area under the curve (iAUC). Fasting venous blood samples were collected to measure serum 1,5-AG, whole-blood hemoglobin A1c (HbA1c) and serum glycated albumin (GA). Clinical markers of glycemia and parameters of glycemic excursions from CGMS were analyzed using the Pearson correlation coefficient and multivariate stepwise regression.

RESULTSPearson correlation analysis revealed that 1,5-AG was significantly correlated with MAGE, SDBG, M-value, LAGE, PPGE and iAUC (r values were -0.509, -0.430, -0.530, -0.462, -0.416 and -0.435, respectively, P < 0.01), especially in moderately and well-controlled patients, based on defined HbA1c levels. Multivariate stepwise regression analysis revealed a negative correlation between 1,5-AG and the above parameters, but not HbA1c and GA. Finally, HbA1c and GA were positively correlated with MBG and fasting blood glucose (FBG).

CONCLUSIONS1,5-AG was much better than HbA1c and GA as a marker of glycemic excursions in type 2 diabetic patients. Based on these results 1,5-AG is the best metric for assessing postprandial glucose levels in moderately and well-controlled patients, while HbA1c and GA were superior to 1,5-AG for monitoring MBG and FBG.

Aged ; Blood Glucose ; metabolism ; Deoxyglucose ; blood ; Diabetes Mellitus, Type 2 ; blood ; metabolism ; pathology ; Female ; Glycated Hemoglobin A ; metabolism ; Humans ; Male ; Middle Aged ; Postprandial Period ; physiology

AIMA series of triazole antifungals were synthesized to search for novel triazole antifungals with more potent activity, less toxicity and broader spectrum.

METHODSNineteen 1-(1,2,4-triazolyl-1H-1-yl)-2-(2,4-diflurophenyl)-3-(4-substituted benzyl-1-piperazinyl)-2-propanols were designed and synthesized, on basis of the three dimensional structure of P450 cytochrome 14 alpha-sterol demethylase (CYP51) and their antifungal activities were also evaluated.

RESULTSAll the title compounds were first reported. Results of preliminary biological tests showed that most of the title compounds exhibited high activity against the eight common pathogenic fungi and the activities against deep fungi were higher than that against shallow fungi.

CONCLUSIONMost of the title compounds showed higher antifungal activities than Fluconazole and Terbinafine. Compound VIII-1, 10, 12, 17 showed best antifungal activity with broad antifungal spectrum and were chosen for further development.

Antifungal Agents ; chemical synthesis ; chemistry ; pharmacology ; Aspergillus fumigatus ; drug effects ; Candida albicans ; drug effects ; Cryptococcus neoformans ; drug effects ; Microbial Sensitivity Tests ; Molecular Structure ; Triazoles ; chemical synthesis ; chemistry ; pharmacology

BACKGROUNDDiabetes has been associated with increased risk of fracture and impaired fracture healing. The aim of this study was to examine the influence of diabetes on perioperative complications, length of stay and ambulatory ability recovery in individuals with hip fracture, and to determine whether changes could be made to improve treatment outcome.

METHODSThe study included 707 hip fracture patients treated at Beijing Jishuitan Hospital between July 2009 and December 2010. The medical history and perioperative complications were compared between non-diabetic and diabetic groups. Length of stay, days awaiting surgery, and days of hospitalization after surgery were also analyzed. Ambulatory ability was compared at 1-year follow-up using the Chi-square test and Fisher's exact test. An independent Student's t-test was used to compare normally distributed continuous data.

RESULTSPatients with diabetes were more likely than non-diabetic patients to develop cardiac perioperative complications (8.9% vs. 3.0%, P = 0.021), urinary tract infections (12.0% vs. 2.8%, P < 0.001), and gastrointestinal symptoms (15.0% vs. 6.8%, P = 0.003). No difference in perioperative complications was observed between the groups. Days awaiting surgery and length of hospital stay were both longer in the diabetic group ((8.0 ± 5.1) vs. (6.2 ± 3.7) days and (16.5 ± 3.8) vs. (13.3 ± 3.8) days, P < 0.001, respectively). Before the occurrence of fracture, patients with diabetes were less likely to be ambulatory outdoors (71.9% vs. 85.9%, P < 0.001) and had more restricted walking ability. After at least 1-year follow-up, similar proportions of patients in the non-diabetic and diabetic groups (16.1% and 15.9%, respectively), who were able to ambulate outdoors before the fracture, became housebound till the final follow-up.

CONCLUSIONSDiabetics are at increased risk of specific complications and have a longer time to surgery and longer in-hospital stay, but generally have similar recovery to non-diabetics thereafter.

Aged ; Aged, 80 and over ; Chi-Square Distribution ; Diabetes Mellitus ; physiopathology ; Female ; Hip Fractures ; physiopathology ; Humans ; Male ; Middle Aged ; Perioperative Period ; Treatment Outcome

OBJECTIVETo compare humoral immune response by co-inoculating mice with antigen HPV16L1 virus-like particle (VLP) and HPV16L1 recombinant plasmids and then observing the neutralizing antibody activity in vitro.

METHODSC57BL/6 mice were injected intramuscularly/subcutaneously with pcDNA-L1 plasmids plus HPV16L1 VLP. Serum IgG levels were detected by ELISA, antibody neutralizing protective activities were determined by hemagglutination inhibition and HPV16L1 VLP binding inhibition assay.

RESULTSSerum antibody titers and neutralizing antibody activities were increased in HPV16L1 plasmids plus HPV16L1 VLP proteins in co-immunized mice when compared with controls.

CONCLUSIONCo-inoculation of the HPV16L1 VLP protein can enhance production of neutralizing antibody activities against aimed antigen, which should be a more promising strategy for effective HPV16 prophylactic vaccine development.

Animals ; Antibodies, Viral ; blood ; Capsid Proteins ; genetics ; immunology ; Erythrocyte Aggregation ; Genes, Viral ; HeLa Cells ; Human papillomavirus 16 ; genetics ; immunology ; Humans ; Immunization ; Immunoglobulin G ; blood ; Mice ; Mice, Inbred C57BL ; Neutralization Tests ; Oncogene Proteins, Viral ; genetics ; immunology ; Plasmids ; Recombinant Proteins ; immunology

BACKGROUNDDiabetes has become one of the most common chronic diseases and the third leading cause of death in China. Many programs have been initiated at national and local levels to address the illness. However, the effect of these programs in daily outpatient clinics is still unclear. The objective of this study was to investigate the management status of type 2 diabetes mellitus (T2DM) and factors associated with it in diabetes clinics of tertiary hospitals in Beijing.

METHODSA cross-sectional survey was conducted in six tertiary hospitals in Beijing. Control criteria were defined based on 2007 China guideline for type 2 diabetes (CGT2D).

RESULTSA sample of 1151 patients, age (60.8 ± 9.2) years, and with a median disease duration of 7.3 years was included. The hemoglobin A1c (HbA1c) mean level was (7.15 ± 1.50)%, the percentage of patients achieving the targets for HbA1c was 37.8%, blood pressure 65.6%, triglyceride (TG) 48.8%, high-density lipoprotein (HDL) 59.2%, low-density lipoprotein (LDL) 34.0%, and total cholesterol (TC) 42.0%. The factors independently associated with glycemic control were diabetes duration (odds ratio (OR) = 0.95; 95% confidence interval (CI): 0.919 - 0.982, P < 0.01), body mass index (BMI) (OR = 0.914, 95%CI: 0.854 - 0.979, P = 0.01) and smoking (OR = 0.391, 95%CI: 0.197 - 0.778, P < 0.01). The factors independently associated with blood pressure control were BMI (OR = 0.915, 95%CI: 0.872 - 0.960, P < 0.01) and male gender (OR = 0.624, 95%CI: 0.457 - 0.852, P < 0.01). The factor independently associated with LDL control was education level (OR = 1.429, 95%CI: 1.078 - 1.896, P = 0.013).

CONCLUSIONSThe management status of T2DM patients in tertiary hospitals in Beijing has improved remarkably. However, there is still room for further improvement to reach the guideline target. Long diabetes duration, high BMI, smoking, male gender and low education level were independently associated with poor metabolic control.

Adolescent ; Adult ; Aged ; Blood Glucose ; metabolism ; Blood Pressure ; China ; Cholesterol ; blood ; Diabetes Mellitus, Type 2 ; blood ; metabolism ; Female ; Glycated Hemoglobin A ; metabolism ; Hospitals ; statistics & numerical data ; Humans ; Lipoproteins, HDL ; blood ; Lipoproteins, LDL ; blood ; Male ; Middle Aged ; Triglycerides ; blood ; Young Adult

OBJECTIVETo observe the exercise single photon emission computed tomography (SPECT) myocardial perfusion imaging of patients with myocardial bridge and assess the association between myocardial ischemia and extent of myocardial systolic compression.

METHODSSeventeen patients with myocardial bridge diagnosed by coronary angiogram were included and underwent exercise SPECT myocardial perfusion imaging.

RESULTSAbnormal SPECT perfusion imaging was evidenced in 12 out of 17 patients with myocardial bridge (2 out of 6 patients with systolic compression induced stenosis < 50%, 3 out of 4 patients with systolic compression induced stenosis between 50% - 75% and 7 out of 7 patients with the systolic compression induced stenosis between 75% - 100%).

CONCLUSIONExercise stress SPECT myocardial perfusion imaging could detect myocardial ischemia in patients with myocardial bridge and abnormal perfusion is positively related to the extent of systolic compression induced stenosis.

Adult ; Aged ; Coronary Angiography ; Exercise Test ; Female ; Heart ; diagnostic imaging ; Humans ; Male ; Middle Aged ; Myocardial Bridging ; diagnostic imaging ; Myocardium ; Technetium Tc 99m Sestamibi ; Tomography, Emission-Computed, Single-Photon ; methods

OBJECTIVETo evaluate the inhibitory effect of Nandeshi, an acrosin inhibitor, on human acrosin activity.

METHODSWe collected sperm samples from 10 healthy fertile men and cultured them with Nandeshi at 30 degrees C for 5 minutes at the concentrations of 0. 100, 0.120, 0.144, 0.173, 0.207, 0.249, 0.299, 0.358 and 0.430 mmol/L, with the controls treated with a well-known acrosin inhibitor N-alpha-p-tosyl-L-lysine chloromethylketone (TLCK) at 150.0, 189.8, 213.6, 240.3, 270.3, 304.1 and 342.1 mmol/L. Then we determined the residual activity of human acrosin by improved Kennedy assay.

RESULTSThe residual activity of acrosin was negatively correlated with the Nandeshi concentration, and Nandeshi exhibited an inhibition rate about 800 times that of TLCK.

CONCLUSIONNandeshi has a powerful inhibitory effect on human acrosin, and improved Kennedy assay is a simple, practical and highly sensitive technique for the detection of human acrosin activity.

Acrosin ; antagonists & inhibitors ; metabolism ; Contraceptive Agents, Female ; pharmacology ; Enzyme Inhibitors ; pharmacology ; Humans ; Male ; Spermatozoa ; drug effects ; Tosyllysine Chloromethyl Ketone ; pharmacology