Objective To investigate the role of nucleotide-binding oligomerization domain-containing protein 1 (NOD1) in inducing insulin resistance in differentiated human adipocytes.Methods Human preadipocytes obtained via liposuction were induced to differentiate into mature adipocytes.iE-DAP,a specific ligand for NOD1,was administered to human adipocytes in culture.NF-κB transcriptional activity and proinflammatory cytokines production were determined by luciferase assay and enzyme-linked immunosorbent assay.Glucose uptake in adipocytes was measured by 2-deoxy-D-[3 H] glucose uptake (P＜0.05).The expression of phosphatidylinositol-3-kinase p85 (PI-3K p85),insulin receptor substrate-1 (IRS-1) and Akt phosphorylations were detected by Western blotting.Results NF-κB transcriptional activity and cytokines such as interleukin (IL)-6,IL-8,and monocyte chemotactic protein 1 secretion were markedly increased after stimulation with iE-DAP (P＜0.05 or P＜0.01).Insulin-induced glucose uptake was decreased with the activation of NOD1 in a dose-and time-dependent fashion.NOD1 activation weakened insulin signal transduction as being revealed by increasing IRS-1 Ser307phosphorylation,reducing protein expression of PI-3K p85,and attenuating insulin-induced phosphorylation of Akt on Ser473 and Thr308in human adipocytes.Conclusion These results indicate that NOD1 activation induces inflammatory response and insulin resistance via IRS-1/PI3-K/Akt signaling pathway in human adipocytes.

Objective To investigate the effects of Saussurea involucrata extract pretreatment on the expression of the Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) in focal cerebral ischemia/reperfusion in mice and its possible neuroprotective mechanism.Methods Seventy-two Kunming mice were randomly divided into four groups:sham operation,saline,Saussurea involucrata extract,and edaravone groups (n =18 in each group).Saussurea involucrata extract 0.8 g/kg was given intraperitoneally in the Saussurea involucrata extract group; edaravone 3 mg/kg was given in the edaravone group; and the same volume of saline was given in the saline group.A model of middle cerebral artery occlusion (MCAO) was induced after 7 days of continuous injection.Cerebral infarct volume was determined by 2,3,5-triphenyltetrazolium staining.Immunohistochemical staining was used to detect TLR4-positive cells in ischemic brain tissue.Reverse transcriptase polymerase chain reaction was used to detect the expression of TLR4/NF-κB mRNA.Results The cerebral infarct volume in mice in the saline,Saussurea involucrata extract and edaravone groups was 131.55± 28.25 mm3,84.10 ±13.92 mm3 and 65.10 ± 6.78 mm3,respectively.There were significant difference (F =10.158,P =0.012).The infarct volume in the Saussurea involucrata extract group (P =0.020) and edaravone group (P0.005) was significantly less than that in the saline group,and there was no significantly difference between the 2 groups.The numbers of cortex and TLR4 positive cells in hippocampus area at the ischemic sides in the saline group were significantly more than those in the sham operation group (all P ＜0.001).The numbers of positive cells of cortex and TLR4 in the Saussurea involucrata extract group and the edaravone group were significantly decreased compared to the saline group (all P ＜ 0.05),and there was no significant differences between the Saussurea involucrata extract group and the edaravone group.The expressions of TLR4,p50,and p65 mRNA in the saline group were significantly up-regulated compared to the sham operation group (all P =0.000).Saussurea involucrata extract could significantly down-regulate the expressions of TLR4,p50,and p65 mRNA at 24 hours after ischemia/reperfusion (all P =0.000).Edaravone could significantly down-regulate the expressions of TLR4 and p65 mRNA (all P =0.000) and it had a down-regulated trend for the expression of p50 mRNA (P =0.053); while there was no significant difference in the expressions of TLR4 and p65 mRNA between the Saussurea involucrata extract group and the edaravone group.Conclusions Saussurea involucrata extract pretreatment may significantly reduce the cerebral infarct volume,down-regulate the expressions of TLR4 and NF-κB subunit,and play a neuroprotective effect by inhibiting inflammatory response after ischemia.

Objective To study the influence of sex on the prognosis in acute ST elevated myocardial in- farction(STEMI)patients after primary percutaneous coronary intervention(PCI).Methods :The risk factors, coronary angiography and prognosis in 478 males and 101 females with STEMl were compared.Results:Mortality of STEMI was significantly different in different age groups(P<0.01).The attack of the STEMI in women was 10 vears later than that of men(P<0.01),especially in those women whose age was over 71 years oId.The complica- tion ratio of hypertension and type 2 mellitus diabetes was higher in female patients than that in male(P<0.01). More multi-vessel lesions were found in female patients than those in male(P<0.01).The incidence of in-hospital mortality,pseudoaneurysm,haematoma Was significantly higher in females than in males(P<0.05.P<0.01).Con- clusions The in-hospital mortalitv and puncture complications in STEMI female patients treated with primary PCI are higher than male patients.

Syndrome and formulae (or prescription) are two key issues in traditional Chinese medicine (TCM) and the premise research for material basis of TCM. However, vagueness of syndromes and complexity of formulae greatly limited the evaluation to syndromes and effective substance basis of prescription. Therefore, how to solve the evaluation of syndromes, confirming the efficacy material basis in prescription are the current hot issues of international concern. To solve these problems, establishing chinmedomics by integrated serum pharmacochemistry of TCM with metabolomics technology, that is a unique method of TCM research, made outstanding contributions in solving international concerns such as the effectiveness and security aspects of TCM. On the basis of the biological characterization of syndrome, the metabolic profiling of animal models of TCM syndrome, and related metabolic fingerprints as well as metabolic biomarkers were established to evaluate the overall effects of TCM formulae and corresponding relationship of syndrome-formulae. The active constituents were screened using the plotting of correlation between (endogenous) marker metabolites and (exogenous) serum constituents (PCMS), and is ongoing verification by further biological experiments. Correlation analysis between the ingredients in the body after oral formulae and endogenous markers in vivo can be used to clarify the active ingredients and synergistic properties. This method was successfully applied for rapid discovery of potentially bioactive components and metabolites from TCM, and through a series of studies on the chinmedomics, it proved that the established method could help to explore the effective substance for further research of TCM. As a new research approach, Chinmedomics is the best method to fit the holistic concept of TCM, and it can not only interpret the essence of syndrome but also elucidate the scientific connotation of Chinese medical formulae.
Animals ; Diagnosis, Differential ; Drug Prescriptions ; Drug Therapy ; Drugs, Chinese Herbal ; analysis ; pharmacokinetics ; Humans ; Medicine, Chinese Traditional

Toxicogenomics (TGx) refers to a set of technologies that assess genome-wide responses after toxic agent exposure. Altered gene expression patterns that are caused by specific exposures reveal how toxicants may disrupt cellular processes and lead to side effects. Development and application of " omics" technology facilitate the toxicogenomic research which sharing and interpretation of the enormous amount of biological information generated in toxicologic field. In recent years TGx has been widely valued and successfully applied as an effective research tool to evaluate the toxic effects of traditional Chinese medicine (TCM). Here we reviewed current progress in the field of TGx and focused on its application in traditional Chinese medicine safety evaluation, especially in revealing the mechanism, finding potential toxic biomarkers and studying compatibility detoxification of TCM.
Medicine, Chinese Traditional ; adverse effects ; Safety ; Toxicogenetics

Objective To report 11 cases with the tissue defects of their upper or lower limbs repaired with the anastomsed medial sural artery perforator flaps.Methods The free medial sural artery perforator flaps,with length of 8 cm to 15 cm and width of 6 cm to 14 cm were used for tissue defect reconstruction of the distal upper or lower limbs in 11 cases,including 6 females and 5 males.The flap was harvested from the ho- mo-lateral calf,confined between the posterior-medial edge of the tibia and the middle line of the calf and a- bove the distal half part of the medial sural muscle,with a same axis of this muscle.Results Ten cases survived very well,which was relatively thin,and the donor site can be acceptable.One case resulted in a complete flap necrotized and covered with a split skin graft.No obvious motor function defect was observed of the donor leg.Conclusion The anastomsed medial sural artery perforator flap is alternative donor flap for the upper or lower limb tissue defect repair,especially for the defect in the hand or foot.

Objective To study expressions of heme oxygenase-1 mRNA and protein in rat hippocampus after hypoxic-ischemia brain damage(HIBD) as well as the relationship with apoptosis in brain.Methods Seven-day-old SD rats were randomly divided into hypoxic-ischemia brain damage group and sham control group.Expressions of HO-1 protein and mRNA as welll as the relationship with apoptosis after HIBD in neonatal rat were determined by immunohisochemistry and in situs hybridizaion as well as terminal deoxynucleotidy transferase mediated UTP-biotin nick end labeling(TUNEL).Results 1.In the right hippocampus,expression of HO-1 gene increased sharply at 4 h (P

Objective - （ ） To explore the influence on the diagnosis of occupational noise induced deafness ONID using three ， Methods versions of diagnostic criteria in 2002 2007 and 2014. A total of 1 766 workers who asked for ONID diagnosis were selected as the research subjects using judgment sampling method. The results of pure tone audiometry were collected. GBZ 49-2002Diagnostic Criteria of Occupational Noise-inducedHearing Loss（ The ONID was diagnosed using hereinafter referred to as GBZ 49-2002），GBZ 49-2007Diagnostic Criteria of Occupational Noise-induced Deafness（ GBZ 49-2007） hereinafter referred to as GBZ 49-2014 Diagnostic of Occupational Noise-induced Deafness（ GBZ 49-2014）， and hereinafter referred to as and the Results - - ， - diagnostic results were compared. Compared with GBZ 49 2002 and GBZ 49 2007 diagnosis with GBZ 49 2014 had （ vs ， vs ， P ）， （ vs ， a higher rate of ONID 57.9% 66.0% 44.8% 66.0% both <0.01 and had a higher rate of mild ONID 47.3% 54.6% vs ， P ） - - 36.0% 54.6% both <0.01 . The diagnostic rate for ONID using GBZ 492014 was higher than those using GBZ 49 2002 and - （ P ）Conclusion - GBZ 49 2007 in each age groups all <0.01 . GBZ 49 2014 improved the diagnostic rate of ONID compared - - with GBZ 49 2002 and GBZ 49 2007. The reason is related to the inclusion of 4 000 Hz hearing threshold with a weight of 0.1 - as the diagnostic hearing threshold and the use of a new age and gender correction method in GBZ 49 2014.

OBJECTIVETo establish the rat model of acute pulmonary embolism, and study the changes of vascular active substances in pulmonary embolism rats, and investigate the interventive effect of anticoagulant drugs on vascular active substances.

METHODSOne hundred and twenty-eight rats were randomly divided into four groups: control group, model group, low-molecular-weight heparin and warfarin treated group and rivaroxaban-treated group (n = 32 in each group). The method of autologous thrombosis was used to establish the animal model of acute pulmonary embolism. The animals were treated with saline or different anticoagulant drugs. The physiological and biochemical parameters were detected at different time points after embolization. The rats were killed after embolism of 24 h, 3 d, 5 d or 1 week respectively and the pathologic samples of lung tissues were collected to analyze the pulmonary pathological changes in different groups.

RESULTSRats in embolization group after blood clots injection showed shortness of breath, oral cyanosis; quicken heart rates and other symptoms. All embolization groups had pulmonary hypertension, the levels of type B natriuretic peptide (BNP) were increased significantly. The ratio of endothelin-1 (ET-1)/NO and thromboxane (TXB2) and prostacyclin (6-k-PGFla) were abnormal. After treated with effective anticoagulant drugs, the levels of BNP, ET-1, NO, TXB2 and 6-k-PGF1a were tended to the normal levels in the control group. The pulmonary hypertensions were gradually decreased. The efficacy of rivaroxaban on pulmonary embolism was the same as that of the low molecular weight heparin or warfarin.

CONCLUSIONAnticoagulation therapy can effectively improve endothelial function after pulmonary embolism, reduce pulmonary hypertension, and revise the increased BNP levels to normal levels. The efficacy of rivaroxaban is not inferior to that of low molecular weight heparin and warfarin.

Animals ; Anticoagulants ; pharmacology ; Disease Models, Animal ; Endothelin-1 ; metabolism ; Heparin, Low-Molecular-Weight ; pharmacology ; Hypertension, Pulmonary ; drug therapy ; metabolism ; Lung ; pathology ; Morpholines ; pharmacology ; Pulmonary Embolism ; drug therapy ; metabolism ; Rats ; Rivaroxaban ; Thiophenes ; pharmacology ; Warfarin ; pharmacology

Adolescent ; Adult ; Aged ; Antiviral Agents ; therapeutic use ; Female ; Hepatitis B, Chronic ; drug therapy ; Humans ; Interferon-alpha ; therapeutic use ; Male ; Middle Aged ; Young Adult