The preclinical safety assessment of hepatotoxicity drugs has a low sensitivity and low specificity. Related tests often generate false negative results and unexpected toxicity,which is one of the major reasons for the cessation of development and withdrawal from the market. Proteomics enjoys advantages of rapidness,high sensitivity and high throughout,and therefore can be used in the search for new biomarkers of hepatotoxicity in preclinical studies,leading to the development of safer drugs and a more efficient drug discovery process. In this review,the current preclinical biomark?ers of liver toxicity and development of proteomic technologies in the discovery and validation of bio?markers of drug-induced liver injury are described,in general the application of proteomics to Chinese medicine-induced liver toxicity in particular. Compared with traditional methods,proteomic technologies show promising results for the discovery of novel hepatotoxic markers. Proteomics,in conjugation with other omics techniques,will play a major role in the early stage of hepatotoxicity screening and will prove to be a good bridge in clinics in the future.

Adult ; Cardiac Catheterization ; adverse effects ; Female ; Heart Septal Defects, Atrial ; therapy ; Hemolysis ; Humans

OBJECTIVE:To understand the status quo adverse drug reactions(ADR) occurred in our hospital and to promote clinical use of drugs.METHODS:By retrospective analysis,study 73 ADR cases collected from our hospital in 2009 were analyzed in respect of gender and age of patient,route of administration,category of drugs,organs and systems involved in ADR and its clinical manifestation.RESULTS:Of total 73 ADR cases,35.6% of cases were induced by anti-infective agents and 9.6% traditional Chinese medicines.Most of cases were caused by intravenous administration.Main clinical manifestations were lesion of skin and its appendents.CONCLUSION:Rational use of anti-infective agents and traditional Chinese medicine(TCM) should be strengthened.Quality control and standard application of TCM injection should be enhanced to reduced or avoid the incidence of ADR.

Objective To non-invasive assess coronary blood flow velocity changes of patients with slow coronary flow phenomenon (SCFP) by coronary blood flow imaging (CFI).MethodsTwenty-one patients who had no significant coronary artery stenosis but had thrombolysis in myocardial infarction (TIMI) slow-flow phenomenon were the experimental group,nine patients who has no significant coronary stenosis and TIMI flow normal were the control group.Using corrected TIMI frame count(CTFC) assess velocity of coronary artery.The left ventricular end diastolic diameter,end systolic diameter,ejection fraction,E peak velocity,A peak velocity,E/A ratio were measured by conventional echocardiography.The distal anterior descending coronary artery diastolic peak flow velocity(Vmax),mean velocity(Vmean) and blood flow velocity time integral(VTI) were measured by CFI.Results The corrected TIMI frame count (CTFC) of left anterior descending artery blood flow in slow blood group was (45.37 ± 8.62)frame,that in control group was (15.94± 4.66)frame,the difference was statistically significant (t = -9.596,P =0.000).The conventional echocardiographic measurements of two groups were not significantly different.The left anterior descending artery Vmax was (22.86 ± 3.04)cm/s,Vmean was (17.62 ± 2.89)cm/s,VTIwas (8.49± 2.01)cm in the slow blood flow group,the left anterior descending artery Vmax was (31.78 ± 9.28) cm/s,Vmean was (23.67 ± 7.60) cm/s,VTI was (10.91 ± 4.47) cm in the control group.The difference was statistically significant.The left anterior descending artery CTFC with Vmax and Vmean was negative correlation in the control group and the slow blood flow group.The left anterior descending artery CTFC was negatively correlated with VTI in the control group,there was no correlation between left anterior descending artery CTFC and VTI in the slow blood flow group.Conclusions Coronary artery flow velocity in the left anterior descending artery was declined.CFI can reflect changes in coronary TIMI flow,but in the diagnosis of coronary slow flow phenomenon CFI has limitations.

Objective To investigate self-management status of the DM patients,and to confirm scientifically the importance of emphasising diabetes education in the DM patients.Methods With the questionnaire on self-management status & the possessed degree of DM knowledge and the method of consulting the medical records,697 DM patients were investigated.Results There were about 47.20% of patients who did not take glycemic examination in one year.Awareness rates for the standards of blood lipids and the HbA_1C were 6.5% and 5.5% respectively.And the awareness rates for nutrition treatment principle and scientific mode of physical exercise were 30.3% and 21.8%,respectively.The prevalence of The DM complications was the highest in the cadre(29.52%) and the lowest in the peasants(3.59%).Conclusion The investigation revealed the self-management is imperfect and the DM knowledge in DM patients is insufficient.It should be accentuated for patients to take health education of DM knowledge and improve their level of self-management.

Ac-Phe-Lys-PABC-DOX (PDOX) is a smart doxorubicin (DOX) prodrug designed to decrease toxicities while maintaining the potent anticancer effects of DOX. This study was aimed at elucidating the effectiveness and toxicities of DOX and PDOX in patient-derived MCF-7 breast cancer cells in vitro. The MCF-7 cells were exposed to both PDOX and DOX, and cytotoxicities, cell cycle and P53/P21 signaling alterations were studied. Abundant cathepsin B was found in the MCF-7 cells, and treatment with PDOX and DOX triggered dose- and time-dependent cytotoxicity and resulted in a significant reduction in cell viability. The IC50 of PDOX and DOX was 3.91 and 0.94 μmol/L, respectively. Both PDOX and DOX caused an up-regulation of the P53/P21-related signal pathway, and PDOX significantly increased expression of P53 and caspase 3, and arrested the cell cycle at the G1/G2 phase. As compared with DOX, PDOX reduced toxicities, and it may have different action mechanisms on breast cancer cells.

Objective To research the combined prognostic utility of NT-proBNP and hs-CTNI in NSTE-ACS risk stratification and early intervention therapy .Methods A total of 245 NSTE-ACS patients were divided to 4 groups(Aa ,Ab ,Ba ,Bb groups) ac-cording to immediate admission NT-proBNP and hs-CTNI .Patients were accepted percutaneous coronary intervention (PCI) ,coro-nary artery bypass grafting and conservative treatment were taken 6 months follow-up .Results The heart failure incidence of Aa group was significantly higher than Ba group(P<0 .05) .6 patients happened left main lesion or multivessel lesion in Aa group were obviously higher than other groups .The incidence of Bb group accepted PCI was obviously higher than Aa group (P<0 .05) .Bb group patients were accepted PCI earlier than other groups ,there was no significance(P>0 .05) .In 6 months follow-up ,5 patients died and 10 patients accepted revascularization again because of severe angina and AMI .Conclusion In NSTE-ACS patient ,NT-proBNP and hs-CTNI elevation was closely related with severe coronary lesions and worse prediction ,which could undergo early in-tervention therapy .

Objective To investigate the analgesic efficacy of ultrasound?guided adductor canal blockade (ACB)after minor arthroscopic knee surgery. Methods Sixty patients undergone minor arthroscopic knee surgery were randomly divided into group ACB(n=20)and group Control(n=20). All patients received spinal anesthesia. The patients in group ACB received ultrasound?gGuided ACB with 20 ml 0.5% ropivacaine,and patients in group Control received 20 ml saline after the surgery. In addition ,all patients have a basic analgesic regimen with etoricoxib. Visual analogue scales(VAS) during rest and passive movement ,additional analgesic dose and side effects were recorded at 4,8,12,24 h Post?operation. At 24 h post?operation,the numbers of patients who can walk for 5 meters were recorded. Results VAS during rest and movement at 4 h,8 h and 12 h post?operation in group ACB were significantly lower than those in group Control. And all patients could walk 5m at 24 h post?operation. No headache,nausea and vomiting,urinary retention and other adverse reactions were observed in group ACB. There were four patients who received additional analgesic and one patient vomitted. Conclusions Significant analgesic effect of the ACB could be detected after minor arthroscopic knee surgery ,with less reduction in requirements for supplemental opioids.

OBJECTIVETo observe the effect of CKJ Recipe (consisting of Cordyceps sinensis polysaccharide, amygdaloside, and gypenosides) containing serum on the activation of rat primary hepatic stellate cells (rHSCs) and to explore its pharmacological mechanism.

METHODSrHSCs were isolated form liver and cultured for four days. Then they were divided into the normal control group, the model group, and the CKJ group. rHSCs in the model group and the CKJ group were treated with 2.5 ng/mL transforming growth factor beta1 (TGF-beta1) in serum-free DMEM for 24 h. Serum free DMEM (containing no TGF-beta1) was taken as the control for the normal control group. rHSCs in the CKJ group were treated with 5% CKJ-containing serum for 24 h. rHSCs in the other two groups were treated with 5% blank serum for 24 h.The protein expression level of a smooth muscle actin (alpha-SMA) was determined using high throughput screening (HCS) and Western blot. mRNA expression levels of alpha-SMA, collagen I (Col-I), platelet-derived growth factor receptor beta (PDGF-betaR), TGF-beta1, transforming growth factor beta receptor 1 (TGF-betaR1), and transforming growth factor beta receptor 2 (TGF-beta R2) were detected using quantitative RT-PCR.

RESULTSCompared with the normal control group, the protein expression level of alpha-SMA, mRNA expression levels of alpha-SMA, Col-I, PDGF-betaR, TGF-beta1, TGF-betaR1, and TGF-betaR2 significantly increased in the model group (P<0.05, P<0.01). Compared with the model group, the protein expression level of alpha-SMA, mRNA expression levels of alpha-SMA, Col-I, PDGF-betaR, TGF-beta1, TGF-beta1, and TGF-beta R2 significantly decreased in the CKJ group (P<0.05, P<0.01).

CONCLUSIONCKJ containing serum could inhibit the protein expression level of o-SMA, which was probably related with inhibiting TGF-beta1 and its related receptors.

Animals ; Cells, Cultured ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hepatic Stellate Cells ; metabolism ; Rats ; Transforming Growth Factor beta ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVETo study the distribution of polymorphism of c.212-37insC (rs3832879) in intron 1 of fibroblast growth factor 23 (FGF23) gene and its association with Kawasaki disease (KD) and coronary artery lesions (CAL).

METHODSForty children with KD were enrolled in this study, among whom 16 children had concurrent CAL. Twenty-six age-matched healthy children were enrolled as controls. PCR and gene sequencing were applied to explore the distribution of polymorphism of c.212-37insC (rs3832879) in FGF23 gene in KD patients and controls.

RESULTSAmong 40 children with KD, 14 (35%) carried the polymorphism of c.212-37insC (rs3832879) in FGF23 gene; among 26 controls, 6 (23%) carried such polymorphism. There was no significant difference in genotype distribution at this locus between the two groups (P=0.30). Among 16 children with CAL, 9 (56%) carried the polymorphism at this locus; among 24 children without CAL, 5 (21%) carried such polymorphism. As for the comparison of two subgroups with and without CAL, the difference in genotype distribution at this locus had statistical significance (P=0.02, OR=4.89, 95% CI: 1.21-19.71).

CONCLUSIONSThe polymorphism of c.212-37insC (rs3832879) in FGF23 gene may not be associated with the pathogenesis of childhood KD, but it may be associated with the development of CAL in children with KD.

Child ; Child, Preschool ; Coronary Artery Disease ; etiology ; genetics ; Female ; Fibroblast Growth Factors ; genetics ; Humans ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; etiology ; genetics ; Polymerase Chain Reaction ; Polymorphism, Genetic