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

Objective To evaluate the clinical applications and surgical methods of combined laparoscopic common bile duct (CBD) exploration with choledochoscopy. Methods From 2006 to 2009,clinical data of 42 patients with choledocholithiasis undergoing laparoscopic common bile duct exploration were retrospectively analyzed. We applied a step-by-step electric coagulating incision technique on the CBD,the step-by-step suturing technique, and the step-by-step clamping technique with alligator forceps, and soft tube irrigating technique with suctioning by selecting the proper exploration route, improving the common bile duct incision technique and calculus removing techniques. Results Procedures were successful in all the cases. There was no conversions to open surgery, no postoperative bleeding and no operative mortality. The mean operating time was 120 minutes (ranging, 90 to 150 minutes) with minimal intraoperative blood loss ( ranging, 20 to 40 ml). Ductal stone clearance was successful in 41 out of 42 patients ( 93% ). The largest number of the common bile duct stones was 16. With the diameter of stones larger than 15 mm in 18 cases in which the biggest was 30 mm. Bile leak developed in 1 patient, retained stones found in 3 patients,including intrahepatic cholelithiasis in one case. As a result, 38 out of 42 patients underwent common bile duct exploration. 35 patients were placed on T-tubes. Four patients underwent cystic duct exploration in which 3 had primary suture of the cystic duct and 1 had drainage. There was no infection and stenosis of biliary tract in the 42 followed-up cases. Conclusions Laparoscopic common bile duct exploration with stone extraction can be performed with high efficiency, minimal morbidity and without mortality. Improving the way of operation and selecting suitable exploration can result in better clinical outcomes.

A new benzene derivative microintegerrin C (1) and a new norsesquiterpenoid microintegerrin D (2), along with six known compounds (3-8), were isolated and identified from stems and leaves of Micromelum integerrimum by various chromatographies such as silica gel, Sephadex LH-20, RP-18 column chromatography and HPLC. Their structures were mainly identified based on the spectral data analysis such as 1D-, 2D-NMR and HR-EI-MS. All known compounds were isolated from this plant for the first time.
Chromatography, High Pressure Liquid ; Plant Leaves ; chemistry ; Plant Stems ; chemistry ; Rutaceae ; chemistry ; Sesquiterpenes ; isolation & purification

As an important neurotransmitter, adenosine displays its functions by acting on the adenosine receptors. Recent studies have shown that the distribution, expression and balance among subtypes of adenosine receptors are closely related with cognitive activities, and changes of adenosine receptors play key roles in neurodegenerative disorders including Alzheimer's disease. It has been pointed out that prolonged activation of adenosine receptors by high level adenosine may lead to the disturbance of balance among adenosine receptor subtypes. This imbalance mainly performed as increased expression of A2a receptor and decreased expression of A1 receptor, and enhancement of the excitatory signals mediated by A2a receptor and weakened inhibitory signals mediated by A1 receptor. Changes of these two subtypes of adenosine receptors may lead to a lot of disorders of neurological activities which developed into dysfunction of cognition to the end. These findings imply that the potential of maintaining the balance among adenosine receptors on the treatment of AD would facilitate both the revealing of the mechanism and the cure of AD.
Adenosine ; physiology ; Alzheimer Disease ; physiopathology ; Humans ; Neurotransmitter Agents ; physiology ; Receptors, Purinergic P1 ; classification ; physiology

Objective To evaluate the therapeutic effects of somatostatin(stilamin)and rhubarb for severe acute pancreatitis(SAP).Method A total of 42 patients with SAP received traditional treatment in combination with somatostatin(stilamin)and rhubarb,and compared with 40 SAP patients with routine treatment.The changes of acute physiology and chronic health evaluationⅡ(APACHEⅡ),serum amylas,serum creatinine,blood calcium,blood glucose,white blood cell count,the duration of abdominal pain,abdominal bulge,fast and hospital stay,complications,morlality and operation rate on the fist day,third day and fifth day were compared between two groups.Results Somatostatin and rhubarb reduced the complications,operation rate and mortality, and shortened the duration of abdominal pain,abdominal bulge,fast and hospital stay.Conclusions Combination of somatostatin and rhubarb is effective in the treatment of SAP patients.

Objective To investigate predisposing factors for early infection in patients with severe acute pancreatitis.Methods The clinical and laboratory data including age、gender、APACHE Ⅱscore on admission、hemodiastase、mechanical ventilation、blood calcium、mean arterial blood pressure、blood glucose、 alanine aminotransferase、aspartate aminotransferase、total bilirubin、necrosis of the pancreas、hypoxemia、 entero-functional disturbance、etiological factor、serum albumin、serum creatinine、urea nitrogen and haematocrit were analyzed by multiple linear regression in relation with the infection incidence in the 86 SAP patients hospitalized from Jan 2002 to Mar 2007.Results The fasting time、hiliary panereatitis、 hypoxemia、necrosis of pancreas、entero-functional disturbance、serum creatinine、urea nitrogen and haematocrit were positively correlated with the incidence of pancreatic infection(all P

Objective To evaluate the value of endoscopic ultrasonography (EUS) in the diagnosis of Crohn's Disease (CD).Methods A total of 436 patients with endoscopically suspected CD underwent EUS and the clinical data of these patients were analyzed retrospectively.Changes of gastrointestinal wall stratification and perienteric complications detected by EUS were documented systematically.The consistency between the diagnosis of EUS and the results of pathology were recorded.Results A total of 297 cases of CD and 139 cases of non-CD were clinically diagnosed,while 277 CDs (including 17 non-CDs clinically diagnosed) and 159 non-CDs (including 37 CDs clinically diagnosed) were diagnosed by EUS.The sensitivity,specificity and accuracy rate of EUS in diagnosing CD were 87.5％ (260/297),87.8％ (122/139) and 87.6％ (382/436),respectively.Dilated vessels in submucosa were detected in 40 patients,fistulae in 13,abscesses in 5 and enlarged lymph nodes in 75.Conclusion EUS can show gastrointestinal wall stratification of CD clearly with high diagnostic accuracy.Meanwhile,EUS can detect extraluminal complications well to help in providing useful information for surgery.

Objective To study the influence of survivin targetedly inhibited with antisense oligonucleotide (ASODN)technique on the apoptosis of hepatoma carcinoma cells SMMC-7221,and to clarify the mechanism of promotion effect of survivin-ASODN on the apoptosis of SMMC-7721 cells.Methods The ASODN sequence of survivin marked by FAM fluorescein was designed and synthized. The SMMC-7721 cells were transfected by different concentrations (100,200,300,400,and 600 nmol· L-1 )of survivin-ASODN (ASODN transfection groups),at the same time blank control group and blank liposome control group and sense oligonucleotide (SODN) control group were set up.The apoptotic rates and the changes of cell cycle of the SMMC-7721 cells 24,48,and 72 h after transfected with different concentrations of survivin-ASODN were detected by FCM. The expression levels of survivin were measured by Western blotting method.Results Compared with each control group,24 h after transfection,the apoptotic rates of survivin-ASODN transfected SMMC-7221 cells were increased,the growth of cells was inhibited (P<0.05),and the effects had time-dose dependent tendency.48 h after transfection,the hypodiploid apoptotic peak appeared in ASODN transfection groups before G1 phase, the number of the cells at G0/G1 phase was decreased (P<0.05)and the number of the cells at G2/M phase wsa increased (P<0.05). Compared with each control group,the survivin expression levels in the SMMC-7721 cells in ASODN transfection groups were decreased (P<0.05 ), and the effects of survivin-ASODN was time-dose dependent (P<0.05 ). Conclusion Survivin-ASODN can block the expression of survivin in SMMC-7721 cells and inhibit the proliferation of SMMC-7721 cells by changing the cell cycle and increasing apoptosis in a time-dose dependent manner.

BACKGROUND: It has been proved that the application of basic fibroblast growth factor (bFGF) combined with Brucea Javanica oil emulsion can accelerate wound healing and inhibit scar formation.OBJECTIVE: To observe the effects of bFGF plus Brucea Javanica oil emulsion cream on accelerating the skin wound healing of rabbits.DESIGN: A randomized controlled observation.SETTING: Center of Biotechnological Research and Development, Jinan University; College of Pharmacy, Jinan University.MATERIALS:The experiment was carried out in the College of Pharmacy, Jinan University from June to September in 2004. Eight Beijing big-ear white rabbits (4 males and 4 females) of 2.0-2.5 kg were provided by the experimental animal center of Southern Medical University (certification number: SoKx-2002-010). bFGF sterile freeze dried powder agent,provided by Guangzhou Changsheng Gene Pharmaceutical Co.,Ltd (batch number: 20040219; specific activity was 6 000 U/bottle), was prepared to solution with water for injection before application. Brucea Javanica oil emulsion (manufactured by Zhejiang 999 Bang'erkang Pharmaceutical Co.,Ltd.) was provided by Professor Yao from staff Room of Pharmacy, Shenyang Pharmaceutical University.METHODS: The rabbits were anesthetized and disinfected, 5 round wounds with diameter of 1.8 cm and area of 2.54 cm2were induced from front to back by bilateral incision at 1.5 cm from middle spine of rabbit. The 5 wounds of each rabbit were randomly divided into bFGF-treated group (90 U/cm2), bFGF+Brucea Javanica oil emulsion group [the wound was smeared with Brucea Javanica oil emulsion (30 mg/cm2) 30 minutes after bFGF (90 U/cm2)], Brucea Javanica oil emulsion treated group [the wound was smeared with Brucea Javanica oil emulsion (30 mg/cm2)], blank emulsion group (30 mg/cm2) and blank control group (the wound was smeared with saline). The medication was give immediately after injury, and changed once a day for 16 days. At 4, 8, 12 and 16 days after injury, the wound areas were recorded with the method of hyaline membrane tracing (the wound was covered with clean saran wrap, the size of wound was traced,and then sheared to be weighed, and converted to calculate the area), and the volume of wounded cavity was measured by infusing water. At 8 and 16 days, the wound tissue was removed, stained after routine tissue sections, and the conditions of growth of granulation tissue and reepithelization on the wound surface were observed.MAIN OUTCOME MEASURE: The wound area, volume of wounded cavity, and the conditions of growth of granulation tissue and reepithelization on the wound surface were obviously at different time points after injury in each group.RESULTS:All the 8 rabbits were involved in the analysis of results. ① Wound areas at different time points in each group: The wound areas in the bFGF+Brucea Javanica oil emulsion group at 4, 8 and 12 days after medication were smaller than those in the blank control group at corresponding time points [(2.05±0.35), (1.59±0.25), (0.55±0.25) cm2;(2.53±0.30), (2.41±0.19), (1.09±0.34) cm2, P＜0.05-0.01]. The wound areas in the bFGF group at 8 and 12 days after medication were (1.71±0.31) and (0.51±0.10) cm2, which were significantly smaller than those in the blank control group at corresponding time points (P＜0.05-0.01). ② Volume of the wounded cavity in each group: The wound volume in the bFGF group at 4 days after injury was markedly smaller than that in the blank control group at corresponding time point [(0.49±0.12), (0.59±0.1) mL, P＜0.05]. The wound volumes in the bFGF+Brucea Javanica oil emulsion group at 4 and 8days after injury were significantly smaller than those in the blank control group at corresponding time points [(0.47±0.12), (0.30±0.08) mL; (0.59±0.1), (0.41±0.07) mL, P＜0.05, 0.01]. ③ Growth of granulation tissue and reepithelization on the wound surface in each group: At 8 days after injury, the inflammatory reaction was milder and fibroblasts proliferated significantly in the bFGF+Brucea Javanica oil emulsion group, and the numbers of capillary plumules and fibroblasts were significantly more than those in the blank control group. The conditions in the blank control group and blank emulsion group were generally the same that there were severe inflammatory reactions, obvious increase of granulation tissue, fewer new capillaries, and unobvious proliferation of epidermic cells. At 16 days after injury, the contraction and reepithelization on the wound surface were obvious, and the new epithelia went towards the wound center rapidly in the bFGF+Brucea Javanica oil emulsion group.CONCLUSION : The application of Brucea Javanica oil emulsion plus bFGF can obviously accelerate the repair of incised wound on the back of rabbits.

OBJECTIVETo study the effect of Jinlida on changes in expression of skeletal muscle lipid transport enzymes in fat-induced insulin resistance ApoE -/- mice.

METHODEight male C57BL/6J mice were selected in the normal group (NF), 40 male ApoE -/- mice were fed for 16 weeks, divided into the model group (HF), the rosiglitazone group ( LGLT), the Jinlida low-dose group (JLDL), the Jinlida medium-dose group (JLDM), the Jinlida high-dose group (JLDH) and then orally given drugs for 8 weeks. The organization free fatty acids, BCA protein concentration determination methods were used to determine the skeletal muscle FFA content. The Real-time fluorescent quantitative reverse transcription PCR ( RT-PCR) and Western blot method were adopted to determine mRNA and protein expressions of mice fatty acids transposition enzyme (FAT/CD36), carnitine palm acyltransferase 1 (CPT1), peroxide proliferators-activated receptor α( PPAR α).

RESULTJinlida could decrease fasting blood glucose (FBG), cholesterol (TC), triglyceride (TG), free fatty acid (FFA) and fasting insulin (FIns) and raise insulin sensitive index (ISI) in mice to varying degrees. It could also up-regulate mRNA and protein expressions of CPT1 and PPARα, and down-regulate mRNA and protein levels of FAT/CD36.

CONCLUSIONJinlida can improve fat-induced insulin resistance ApoE -/- in mice by adjusting the changes in expression of skeletal muscle lipid transport enzymes.

Animals ; Apolipoproteins E ; deficiency ; genetics ; Blood Glucose ; metabolism ; CD36 Antigens ; genetics ; metabolism ; Carnitine O-Palmitoyltransferase ; genetics ; metabolism ; Dietary Fats ; adverse effects ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Hypoglycemic Agents ; administration & dosage ; Insulin ; metabolism ; Insulin Resistance ; Lipid Metabolism ; drug effects ; Male ; Metabolic Diseases ; drug therapy ; enzymology ; genetics ; metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Muscle, Skeletal ; drug effects ; metabolism