The leading cause of drug withdrawal from market and clinical trials failure is drug-induced liver injury (DILI). Varying clinical, histological and laboratory features of DILI, as well as undefined underlying mechanisms, hinder patients to be diagnosed in the early-stage of the disease and receive effective treatments. Conventional indicators, like serum transaminases and bilirubin, have inevitable limitations referring to sensitive prediction and specific detection of DILI. In order to reduce the occurrence of DILI, researchers have attempted to discover potential biomarkers with higher specificity and sensitivity from blood and urine in recent years. This article aims to review recent advances in biomarkers of DILI.
Biomarkers ; blood ; urine ; Chemical and Drug Induced Liver Injury ; diagnosis ; Humans ; Sensitivity and Specificity

AIM:To explore the expression and possible function of histamine H3 receptor (H3R) in striated myogenesis and the differentiated C2C12 cells.METHODS: H3R and myogenesis late marker myosin heavy chain (MHC) were detected at mRNA and protein levels during C2C12 myogenesis.H3R antagonist ciproxifan was added and the expression of the myogenesis early marker desmin, intermediate markers myogenin and MHC was detected.Differentia-ted myoblasts were loaded with Fluo-4 calcium indicator dye and the effect of R-( a)-methylhistamine ( RMeHA) on the cy-toplasmic calcium concentration was determined under the 200 mA electrical stimulation.RESULTS: The expression of H3R and MHC was increased during myogenesis.Ciproxifan incubation had no influence on the 3 striated myogenesis mar-kers (P>0.05).In C2C12 myoblasts, RMeHA (10 nmol/L~100 μmol/L) effectively diminished cytoplasmic calcium peak when the cells were electrically paced (P<0.05).The best inhibitory effect of RMeHA was observed at dose of 100 nM for 10 min and 20 min, which was higher than that for 5 min (P<0.05).CONCLUSION: H3R might have little effect on the myogenic differentiation, but diminishes cytoplasmic calcium peak of the differentiated myoblasts under electri-cal stimulation.

AIM: To observe the clinical effects of intravitreal injection of triamcinolone acetonide ( TA ) before vitrectomy for retinal detachment associated with choroidal detachment. · METHODS: Totally 23 cases ( 23 eyes ) of retinal detachment associated with choroidal detachment in our hospital were treated by intravitreal injection of TA 4-5d before 23-Gauge micro-invasive vitrectomy combined with silicone oil injection. All the cases were followed up between 6 to 9mo. The anatomic retinal reattachment, visual acuity, intraocular pressure and postoperative complications were observed and analyzed. ·RESULTS: After the surgery, the visual acuity of all patients were improved, with 9 eyes better than 0. 3 (39%), and 18 eyes better than 0. 05 (78%). The BCVA at 1wk, 1 and 3mo and last follow up were different compared with before operations (P<0. 05). The mean intraocular pressure was 4. 02±1. 47mmHg before injection, 13.69±4. 68mmHg before operation (P<0. 05), and17.72±5.87 mmHg after operation (P<0.05). The retina of all patients treated were reattached 2wk post-operatively. The retinal reattachment rate after the primary surgery and the secondary surgery was 87% and 100%, respectively. Post-operative complications included 7 eyes of transient high intraocular pressure, occurred during 12-14d after operations and returned to normal after less glucocorticoid eye drops and giving IOP lowering drugs. There were no intraocular hemorrhage, iatrogenic retinal breaks, infections, or lens injuries. · CONCLUSION: Intravitreal injection of TA before vitrectomy for retinal detachment associated with choroidal could improve the clinical effects, and decrease the difficulty of surgery while the injection itself is pretty safe.

AIM:To observe the efficacy and safety of 1g/L bromfenac sodium hydrate ophthalmic solution in the partial substitution of glucocorticoid after laser subepithelial keratomileusis (LASEK).METHODS: Totally 104 cases (208 eyes) were received LASEK, which were selected and divided into study group and control group.The study group were adopted 1g/L bromfenac sodium hydrate ophthalmic solution combined with tobramycin dexamethasone eye drops and fluorometholone eye drops, the control group were adopted tobramycin dexamethasone eye drops and fluorometholone eye drops.The changes of visual acuity and intraocular pressure of two groups were recorded before and after surgery, and the score of painness and the occurrence of haze were observed after surgery.RESULTS: At postoperative 1, 2, 3d, respectively, the pain score of the study group were 1.70±0.35, 1.25±0.34, 0.82±0.32, the pain score of the control group were 2.30±0.43, 1.68±0.44, 1.12±0.33, the differences were significant (P<0.05).Before and at 2wk, 1, 3mo after surgery, respectively, uncorrected visual acuity of study group were 0.035±0.02, 0.71±0.13, 0.89±0.17, 0.88±0.18, while which of control group were 0.037±0.015, 0.73±0.15, 0.87±0.14, 0.86±0.15 (P>0.05), and the differences were not significant(P>0.05).At preoperative and postoperative 1, 2wk, 1 and 3mo of surgery, respectively, the intraocular pressure of study group were 17.33±1.58, 7.54±1.28, 7.23±1.58, 7.26±1.47, and 7.30±1.36 mmHg;the intraocular pressure of control group were 17.53±1.43,7.57±1.32,7.73±1.55,7.80±1.38,7.86±1.43 mmHg,the differences were not significant between before and at 2wk after surgery(P>0.05), the differences were significant between the two groups at 2wk, 1mo and 3mo (P<0.05).At postoperative 1, 3mo of surgery, the score of haze level of the study group were 91.7% and 93.3%, respectively and which in control group were 92.0% and 92.9%, respectively, and the differences were not significant between the two groups at every time point(P>0.05).CONCLUSION: It is safe and effective that 1g/L bromfenac sodium hydrate ophthalmic solution in the partial substitution of glucocorticoid after laser subepithelial keratomileusis.The patient has a lower intraocular pressure, has similar therapeutic effect as glucocorticoid in vision and antiinflammatory.

Objective:To explore the relationship between development of social skills and executive function and theory of mind in children and adolescents with autism.Methods:Forty-six children and adolescents with autism aged 6 to 17 years were recruited.The diagnosis was made according to the Diagnostic and Statistical Manual of Mental Disorder,Fourth Edition(DSM-Ⅳ),and severe mental disorders were excluded by the screening of the Schedule for Affective Disorders and Schizophrenia for School-Age children (K-SADS).The Rey Complex Figure Test (RCFT),Trail-Making Test,Verbal Fluency Test,Stroop Color-word Task,the First-Order Belief Test and the Second-Order Belief Test were used to assess executive function and theory of mind,and Social Response Scale (SRS) was used to assess social skills.The correlation between results of Executive Function and SRS was analyzed.The SRS scores between groups passing and without passing of First-Order Belief Test and Second-Order Belief were compared.Results:In the aspect of Executive Function,RCFT scores were positively correlated with autistic behavior factor score of SRS (r =0.31-0.41,Ps ＜ 0.05),meanwhile,immediate recall structure scores of RCFT were positively correlated with social motivation factor scores of SRS (r =0.30,P ＜ 0.05),delayed recall structure scores of RCFT were positively correlated with SRS total scores(r =0.34,P ＜ 0.05).In Stroop Colorword Task,errors of the first task were positively correlated with social cognitive factor scores of SRS (r =0.32,P ＜ 0.05).There were no correlation between other Executive Function results and SRS scores (r =-0.21-0.24,Ps ≥0.05).In the aspect of Theory of Mind,there was no significant difference in SRS scores between groups passing or without passing (t =-0.68-1.73,Ps ≥ 0.05).Conclusion:The development of social skill in children and adolescents with autism may have relationship withexecutive function,but have no relationship with the theory of mind.

Objective To estimate the difference of PS、CBV/CBF in the evaluation pf angiogenesis and growth behavior of the C6 glioma.Methods Sixty adult Wistar rats were divided into 3 groups randomly.CT perfusion were performed at the time of 5,13,20 d after the rats were inoculated C6 glioma cells.Permeability surface(PS),cerebral blood volume(CBV),cerebral blood flow(CBF)of different part of the tumor(central part,peripheral part,adjacent part and contralateral normal parenchyma)were measured at different time.Results At the central parts of the lesions,there were obvious difference between different time of tumor growth among PS[(3.94?0.15),(8.47?0.34),(5.20?0.65)ml? 100g~(-1)?min~(-1)],CBF[(280.33?8.82),(388.33?14.00),(116.16?11.54)ml? 100g~(-1)?min~(-1)],CBV[(7.75?0.27),(12.73?0.98),(5.14?0.66)ml?100g~(-1)](F=4.421,P= 0.013;F=11.370,P=0.000;F=15.789,P=0.000).There were statistical difference of PS at the different time in both the peripheral and adjacent parts of the glioma.(F=13.567,P=0.000;F=12.470, P=0.000).No difference were detected in CBF or CBV at different time of the peripheral parts of the tumors(F=1.176,P=0.336;F=0.148,P=0.710).there were significant difference between different time of tumor growth among CBF[(175.33?12.95),(275.50?13.76),(246.33?12.81)ml? 100g~(-1)?min~(-1)],CBV[(4.15?0.47),(8.05?0.30),(7.54?0.89)ml?100g~(-1)]at the adjacent parts of the tumors(F=24.176,P=0.000;F=17.148,P=0.000;F=15.791,P=0.000). Coneluslon CBV,CBF can reflect the number and volume of the tumor vessels,while PS can directly reflect the function of the angiogenesis and the behavior of the glioma.

AIM:To point the susceptible gene in Avellino corneal dystrophy family with autosomal dominant inheritance.
●METHODS: Genomic DNA was extracted from the peripheral blood samples of all individuals of the pedigree. Several microsatellite makers were selected for gene scan in the hot regions of mutation. Linkage analysis was carried out using a Linkage software package. The haplotype data were processed using Cyrillic software to define the region of the disease gene.
●RESULTS: ln our pedigree, significant evidence of linkage was obtained at marker D5S396 and D5S393 [LOD score (Z)=3. 01, recombination fraction (θ)=0. 00]. The haplotype analysis of our pedigree was located between the microsatellite markers D5S808 and D5S638.
●CONCLUSION:The pathogenic gene of the Avellino corneal dystrophy pedigree is traced to a 11. 2 cM region in the chromosome 5q.

Objective To discuss a real-time fluorescence quantitative polymerase chain reaction (FQ-PCR) wether if can be used to detect Brucella. Methods According to the BCSP31 gene sequences specific for Brucella, one pair of primers and one TaqMan probe were designed. A real-time PCR was developed with the BCSP31 fragments cloned into PMD18-T vector. The standard cure was established and the sensitivity, the species specificity and the stability of the assay were evaluated. The clinical blood specimens were detected by QT-PCR and compared with clinical diagnosis. Results The standard curve was established with the standard template and the relationship between the Ct and the DNA copy number was linear(r=0.999). The sensitivity of the real-time PCR was 5 copies/μl. The sensitivity of the common PCR was 5×102 copies/μl. The sensitivity was about 100 times higher than common PCR. Species specificity of this FQ-PCR assay evaluated using genomic DNA from 6 Bmcella strains and 5 non-Brucella strains and strong fluorescence was detected in all Brucella strains. The CV of intra-assay and inter-assay reproducibility were 0.71%,7.23%, reprectively. Twenty-four specimens from clinical brucellosis cases, 19 showed positive, the positive coincident rate was 79%(19/24). The negative results were obtained for all 31 negative control, and the negative coincident rate was 100%(31/31). Two were positive from all 30 specimens clinically suspected. Conclusions Highly specific, sensitive, repeatable and coincidental with clinic, this FQ-PCR is quite useful for rapid detection of tiny DNA of Brucella in various samples and laboratory diagnosis.

OBJECTIVETo follow up the cohort of a certain factory and analyze the death cause of the employees.

METHODSA dynamic cohort was adopted and the study population consisted of all workers stayed at the factory for more than 1 year. The cohort data was mainly from the personnel ministry in the factory,the death data provided by the personnel ministry,the labour union and the hospital. All cause of death of the all employee and the death condition of radiation group and no-radiation group were analyzed and compared.

RESULTSThe mortality of the workers in the factory was significantly lower than national population, the SMR of all cause of death in all employee, radiation group and no-radiation group were 0.41 (95% CI: 0.37-0.45), 0.24, 0.75 respectively; all cancer death in the three group was 0.59, 0.40 and 0.92. But the death order was different in radiation group and no-radiation group,the order of liver cancer was list first in radiation group, which was unlike that of the nation order and the no-radiation order.

CONCLUSIONThere have no excess death in the factory, but the order of liver cancer is precedence.

Cause of Death ; Cohort Studies ; Female ; Humans ; Male ; Middle Aged ; Neoplasms, Radiation-Induced ; mortality ; Nuclear Reactors ; Occupational Exposure ; Power Plants ; Prospective Studies ; Workplace

To study the chemical constituents of the 95% ethanol extract of Psidium guajava. Compounds were separated by using a combination of various chromatographic methods including silica gel, D101 macroporous resin, ODS, Sephadex LH-20 and preparative HPLC. Their structures were elucidated by physicochemical properties and spectral data Eighteen compounds were isolated and identified as (+) -globulol (1), clovane-2beta, 9alpha-diol (2), 2beta-acetoxyclovan-9alpha-ol (3), (+) -caryolane-1 ,9beta-diol (4), ent-T-muurolol (5), clov-2-ene-9alpha-ol (6), isophytol (7), tamarixetin (8), gossypetin (9), quercetin (10), kaempferol (11), guajaverin (12), avicularin (13), chrysin 6-C-glucoside (14), 3'-O-methyl-3, 4-methylenedioxyellagic acid 4'-O-beta-D-glucopyranoside (15), p-hydroxy-benzoic acid (16), guavinoside A (17) and guavinoside B (18). Compounds 2-9 and 14-16 were isolated from this plant for the first time. The ethanol extract showed 61.3% inhibition against the proliferation of colon cancer cell line SW480.
Drugs, Chinese Herbal ; chemistry ; Organic Chemicals ; analysis ; Plant Leaves ; chemistry ; Psidium ; chemistry