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

OBJECTIVETo compare the effect of reinforcing Shen method (RSM) and activating blood method (ABM) in treating osteoarthritis (OA) at the molecular level.

METHODSThe physical and chemical characteristics of components from respective recipes of RSM and ABM, and network features of component-target interaction network were analyzed by computer simulation methods including chemical space, molecular docking, and biological network, etc.

RESULTSThe chemical components of RSM and ABM were scarcely scattered with larger overlapping. Among established networks, the distribution of network features was partially similar in RSM and ABM. The average target number correlated with each component was 1.86 in RSM and 2.11 in ABM respectively. Each average target number was respectively correlated with 4.46 compounds and 3.93 compounds, reflecting multi-component and multi-target actions.

CONCLUSIONComputer simulation could intuitively trace out similarities and differences of two different methods and their interaction with targets, which revealed that the compatibility of RSM and ABM could have broader protein targets and potential synergism at the molecular level.

Computer Simulation ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Humans ; Osteoarthritis ; drug therapy ; Phytotherapy ; methods

OBJECTIVETo evaluate the prognostic effects of neoadjuvant chemotherapy (NAC) in patients with local advanced gastric cancer.

METHODSWe retrospectively analyzed prognosis in 191 patients with advanced gastric cancer, of whom 71 were treated with NAC and 120 received surgery only between February 2007 and July 2013. Postoperative complication rate was recorded. Survival by clinicopathological features, pathological T and N stages, and histopathological tumor regression was retrospectively compared between the two groups.

RESULTSAccording to Response Evaluation Criteria in Solid Tumors, none of the 71 patients in the NAC followed by surgery group showed complete response, 36 showed partial response, 25 had stable disease, and 10 had progressive disease. The chemotherapy response rate was 50.7%; the disease control rate was 85.9%. Grade 3/4 adverse events were seen in less than 20% patients, with acceptable toxicities. No difference was found in the overall postoperative complication rates between the two groups (7 versus 22 cases, P=0.18). Median survival time was significantly different, at 54 months in the NAC combined with surgery group and 25 months in the surgery-only group (P=0.025).

CONCLUSIONIn patients with operable gastric adenocarcinomas, NAC can significantly improve overall survival without increasing surgical complications.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Prognosis ; Retrospective Studies ; Stomach Neoplasms ; drug therapy ; mortality ; pathology

OBJECTIVETo explore the material basis of Caulis sinomenii (CS) in treating osteoarthritis (OA), and to give a pharmacodynamic illustration for the multi-targeting therapeutics of CS.

METHODSThe computational methods, consisting of molecular docking and biological network were carried out to search the database targeting twelve important OA related enzymes: ASAMTS4, ASAMTS5, MMP-1, MMP-3, MMP-13, MMP-8, MMP-2, COX-2, COX-1, IL-1beta, TNF-alpha, iNOS, and map the ligand-target interaction networks about molecules from CS and DrugBank. After that, an aggregate analysis was performed to analyze the mechanisms of compositions in CS.

RESULTSTotally 14 had good interaction in all molecules in database with two or more than two of the OA correlated enzymes, and 6 molecules had interaction with four or more enzymes. Moreover, both herb ligand-target interaction network and drug ligand-target interaction network were similar in the interaction profiles and network features, which revealed multi-drugs effects in CS.

CONCLUSIONSThere were a lot of multi-target molecules in CS, providing pharmacodynamic illustrations for the multi-target therapeutics of Chinese medicine. Meanwhile, they supplied certain reference and inspiration for finding out new drugs for OA therapy.

Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Molecular Docking Simulation ; Osteoarthritis ; drug therapy ; Phytotherapy ; Sinomenium

AIM: To screen TIGR/myocilin gene (MYOC) mutation in high myopic Chinese children with family history.METHODS: Gene sequencing was performed in exon 3 of the TIGR gene in high myopic Chinese Children. The coding sequence of TIGR exon 3 was screened by capillary electrophoresis sequencing. The sequence alterations were analyzed by bioinformatics.RESULTS: TIGR gene mutation was not found in high myopic patients and normal controls group.CONCLUSION: No identified gene mutation is found in TIGR gene in high myopic Chinese children.

OBJECTIVETo compare the effect of transumbilical single-site single-port with that of transumbilical single-site double-port laparoscopic varicocelectomy in the treatment of varicocele in adolescents.

METHODSWe randomly assigned 80 varicocele patients aged 10 - 16 years to two groups of equal number to receive transumbilical single-site single-port and single-site double-port laparoscopic varicocelectomy, respectively. We compared the operation time, postoperative hospital stay, incisional pain, complications and satisfaction with the abdominal cosmetic outcomes between the two groups.

RESULTSAll the operations were successfully performed. The double-port group showed a significantly higher score on the Visual Analogue Scale than the single-port group (4.8 +/- 1.4 vs 3.6 +/- 1.1, t = -4.986, P < 0.01), but there were no significant differences between the two groups in the operation time ([29.8 +/- 4.2] vs [31.2 +/- 4.6] min, t = 1.383, P = 0.171), postoperative hospital stay ([1.95 +/- 0.7] vs [1.82 +/- 0.8] d, t = -0.784, P = 0.436), complications (0 vs 0) and scores on the satisfaction with abdominal cosmetic outcomes (4.6 +/- 0.6 vs 4.8 +/- 0.5, t = 1.253, P = 0.214). No recurrence, umbilical hernia, hydrocele and orchiatrophy were found in the two groups of patients at 6 months after operation, and no visible scar was observed on the abdominal surface.

CONCLUSIONWith strict surgical indications, single-site single-port and single-site double-port laparoscopic varicocelectomies have similar clinical effects in the treatment of varicocele, which leave no scar on the abdominal surface. Single-site double-port laparoscopy needs no special instruments and therefore is worthier of wide clinical application.

Adolescent ; Child ; Humans ; Laparoscopy ; methods ; Length of Stay ; Male ; Operative Time ; Umbilicus ; surgery ; Varicocele ; surgery

Objective To investigate the regional left ventricular function after mitral valve replacement with and without chordal preservation by strain rate imaging. Methods A total of 55 patients undergoing mitral valve replacement were enrolled. Twenty underwent complete excision of the subvalvular apparatus (group A), 20 preserved the posterior chordopapillary apparatus only (group B) and the other 15 underwent total chordal preservation (group C). Systolic peak strain rate (SRs) were measured preoperatively, at 7-10 days and 3 months after operation. Results Before operation, SRs had no differences between different segments of the left ventricular in each group (F=0.37, 0.74, 0.90, all P>0.05). At 7-10 days after operation, SRs in the most segments of left ventricular were signiifcantly lower than those of before operation (F=3.91, 8.12, 7.57, all P<0.05). At 3 months after operation, SRs in some segments of left ventricular were signiifcantly higher than those of preoperation in each group (t=2.12, 3.19, 3.25, 2.08, 2.78, 4.79, 2.81, 2.58, 2.87, 1.60, 0.34, 1.04, 0.73, 0.70, 1.68, all P<0.05). SRs had no signiifcant differences between each segment of left ventricular in group C (F=1.76, P>0.05). By contrast, SRs in some segments of left ventricular were different from those of other segments in group A and group B (F=17.8, 8.52, both P<0.05). Conclusion Comparing to conventional mitral valve replacement and mitral valve replacement with preservation of posterior subvalvular apparatus, mitral valve replacement with preservation of total subvalvular apparatus makes the papiltary function preserved completely, which are beneifcial for the motor coordination of left ventricular wall and the recovery of regional left ventricular function.

OBJECTIVE: To study the expression of c-fos in organs after rats electrified. METHODS: The brain, lung, heart, liver, spleen, kidney, muscle of electrified limb, and cutis of electrified limb of all experimental rats and those organs of control groups were dissected to detect the expression of c-fos by using immunohistochemistry staining, and the staining intensity were assessed by image analysis system. RESULTS: The expression of c-fos was observed in brain, heart, liver, lung, kidney and muscle in electrified directly group, the amount of expression reached peak at 2 h after electrified and decreasing at 8 h after electrified, and the expression showed faintness in electrified at the immediate after death group. The expressions of c-fos in spleen and cutis is negative in all groups. The expression of c-fos in all detected organs was negative in other rats that were electrified after death. CONCLUSION c-fos can be regard as a target in identifying electrical injury, whether it formed at antemortem or postmortem.
Animals ; Brain/pathology* ; Death ; Disease Models, Animal ; Electric Injuries/pathology* ; Immunohistochemistry ; Kidney/metabolism* ; Liver/metabolism* ; Lung/pathology* ; Male ; Myocardium/pathology* ; Proto-Oncogene Proteins c-fos/metabolism* ; Rats ; Rats, Sprague-Dawley ; Staining and Labeling ; Time Factors

Interleukin-2 (IL-2) therapy often results in potentially life-threatening side effects including hypotension. However, the mechanism has not been completely elucidated. In order to determine whether IL-2 modifies vascular tone, we investigated the effect of IL-2 on rat thoracic aorta rings and the underlying mechanisms. Effects of IL-2 on the contraction of high KCl and phenylephrine (PE) preconstricted rat thoracic aorta with or without endothelium were determined by organ bath technique. To explore the mechanism, nitric oxide synthase inhibitor L-N(G)-nitroarginine methyl ester (L-NAME), guanylyl cyclase inhibitor methylene blue, and cyclooxygenase inhibitor indomethacin were used. IL-2 (10-1000 U/ml) caused concentration-dependent relaxation of aorta rings preconstricted with PE (10 micromol/L) in endothelium-intact rings, but had no effect on KCl (120 mmol/L) preconstricted rings. Removal of the endothelium, or pretreatment with L-NAME (0.1 mmol/L) or methylene blue (10 micromol/L) or indomethacin (10 micromol/L), inhibited the relaxation of IL-2. The results indicate that the relaxation by IL-2 in rat aorta ring is endothelium-dependent and is possibly mediated by the NO-guanylyl cyclase pathway and cyclooxygenase-dependent pathway.
Animals ; Aorta, Thoracic ; drug effects ; physiology ; Endothelium, Vascular ; drug effects ; Endothelium-Dependent Relaxing Factors ; pharmacology ; Guanylate Cyclase ; metabolism ; In Vitro Techniques ; Interleukin-2 ; pharmacology ; Male ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitric Oxide ; metabolism ; Prostaglandin-Endoperoxide Synthases ; metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Vasodilation ; drug effects ; Vasodilator Agents ; pharmacology

OBJECTIVETo investigate the effect of interleukin-2 (IL-2) on myocardial impairment during ischemia/reperfusion or anoxia/reoxygenation.

METHODSChemical anoxia was introduced in the isolated rat ventricular myocytes by Krebs-Henseleit (K-H) solution containing 10(-3) mol/L sodium dithionite. The video-tracking system and spectrofluorometric method were employed to verify the cell contraction and calcium homeostasis of the single myocyte. Radioimmunoassay was used to analyze the IL-2 levels in myocardium.

RESULTSThe levels of IL-2 in myocardium subjected to ischemia/reperfusion were elevated [(14.34+/-5.99 compared with 22.25+/-3.68)ng/g, P<0.01]. During anoxia, cell contraction and the amplitude of electrically induced calcium transient were depressed and the parameters did not return to the pre-anoxia level during reoxygenation. IL-2 at 200 U/L administered during anoxia aggravated the effect of reoxygenation on cell contraction and calcium transient. After perfusion with IL-2, the malondialdehyde content of myocardial mitochondria was elevated.

CONCLUSIONCoexistence of IL-2 during anoxia aggravates the effect of reoxygenation on the cell contraction and calcium homeostasis in the isolated rat ventricular myocytes, in which the mitochondrial lipid peroxidation induced by IL-2 is involved.

Animals ; Calcium ; metabolism ; Interleukin-2 ; physiology ; Lipid Peroxidation ; Male ; Malondialdehyde ; blood ; Mitochondria, Heart ; metabolism ; Myocardial Ischemia ; physiopathology ; Myocardial Reperfusion Injury ; physiopathology ; Rats ; Rats, Sprague-Dawley