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.

Objective To establish a rapid assay for genotyping of IL-6-597G/A and-572G/C polymorphisms by duplex real-time PCR assay.Methods One pair of primers and two pairs of fluorescent hybridization probes had been used to genotype two mutation sites in the promoter region of IL-6 gene by fluorescent resonance energy transfer and melting curves.Results Duplex real-time PCR method for genotyping of two mutation sites simultaneously had been developed and 123 health people samples were analyzed by this new method.The results showed that three genotypes were found in IL-6 gene-572G/C polymorphisms.They were GG,GC and CC genotypes.IL-6 gene promoter-597G/A polymorphism analysis showed 4 cases displayed GA genotype and other possessed GG genotype.No AA genotype had been found.Conclusions Duplex real-time PCR method is simple and fast.It provided an accurate and economic method which is suitable for clinical gene genotyping.

BACKGROUND: Current research of mechano growth factor (MGF) mainly focuses on the muscles and nerve damage and repair, and it has bean confirmed that MGF can promote muscle cell hypertrophy and nerve repair significantly. Regarding its role in fracture healing is unclear. OBJECTIVE: To investigate the effect of MGF on radial fracture healing in rabbits. METHODS: By using random digital table method, 12 New Zealand rabbits were divided into 3 groups: blank control group, low-dose MGF group and high-dose MGF group. The models with 5 mm bone defect were produced in the middle of the left radius in rabbits. At 3 days after the surgical operation, the defective areas were given 0.2 mL PBS or 0.2 mL MGF (0.36 and 0.72 g/L) injected into the ends of fracture areas, respectively, once per day for continuous 5 days. At 4, 6, 8 weeks after operation, X-ray photography was used to evaluate the healing of fracture, and the histological examinations were performed at the 8~(th) weak to observe the call morphology at the fracture lesion. RESULTS AND CONCLUSION: At 1 day after operation, the activities of rabbits were reduced, with slightly reduced food intake, at 2 days they almost recovered to normal activities and diet. At 3 days, the surgical incision slightly swelled with a small amount of bleeding and without obvious signs of infection. All 12 rabbits entered the final analysis. X-rays showed that two fracture ends have basically combined in the high-dose MGF group at 4 weeks post-surgery, cortical bone was continuous and fracture lines were unclear. At 6 weaks the bone medullary cavity almost run through and fully run through at 8 weeks. The healing time in the high-dose MGF group was remarkably shorter than that in blank control group and low-dose MGF group, the healing was in high quality. At 8 weeks after operation, a large number of osteoid tissues were observed in the blank control group, a small amount of woven bone formed, at a transition period from the fibrous bone callus to the bony bone callus; a large number of woven bone formed inthe low-dose MGF group, at bony bone callus period; in the high-dose MGF group, a large number of woven bones converted into mature lamellar bone, at the callus rebuilding phase, which was consistent with imaging results. It is indicated that MGF can accelerate fracture healing significantly in a rabbit model and shows a dose-dependent manner in a certain range.

Objective To analyze the predictive factors of fever after percutaneous renal stone surgery,and to provide reference for clinical treatment.Methods A total of 147 patients underwent percutaneous nephrolithotomy in after operation was chosen in the Department of Urology in our hospital from January 2014 to January 2016.According to the existence of fever,patients were divided into fever (n =25,heating rate 17.0％) and control (n =122) groups.Preoperative information were collected,including age,gender,preoperative serum creatinine,stone size and shape,the involvement of calyceal number,water,urine culture results,operative time,blood loss,intraoperative perfusion volume,pyonephrosis,puncture channel length,hospitalization time and other information including intraoperative,postoperative information including fever,and postoperative renal fistula complications if there is information.SPSS 18.0 was used for statistical analysis.Results The fever group stone surface area,CT value affected calyx number,stone shape,stone properties,the involvement of calyceal number,degree of hydronephrosis,operative time,intraoperative blood loss,intraoperative perfusion,hospitalization time,and renal fistula complication rates were higher than the control group (P ＜ 0.05).There were no significant differences between two groups (P ＞0.05).The results of Logistic regression analysis found that the stone surface area (OR =5.19),stone,stone shape (OR =7.86) properties (OR =3.87),operation time (OR =5.68),intraoperative perfusion (OR =5.24),and renal fistula complications (OR =2.65) for the influence factors of fever.Conclusions The stone surface area is large,stone nature infection stones,stone shape for staghorn calculi,longer operation time,and intraoperative perfusion of large renal fistula complications were more prone to postoperative fever in postoperative.

Objective To explore the high risk factors of brain injury in preterm infants,and to reduce its morbidity and improve the developmental outcome.Methods One hundred and thirty preterm infants,who were admitted to our neonatal intensive care unit(NICU)between Aug.2005 and Aug.2007,were scanned by echo in 1,3,4,7,15 days,and 1,3 and 6 months after birth,respectively.Those who had intraventricular hemorrhage(IVH)of grade Ⅰor Ⅱ were regarded as mild brain injury,whereas those who had IVH of grade Ⅲ or Ⅳ or periventricular leukomalacia(PVL)were regarded as severe brain injury.Logistic regression was adopted to analyze 17 factors:gestational age,birth weight,hypertension syndrome during pregnancy,premature rupture of membranes,modalities of delivery,fetal distress,asphy-xiate,resuscitation,surfactant,apnea,seizures,hypoxia,hypercarbia,hypocarbia,acidosis,use of oxygen,nasal constant positive airway pressure or mechanical ventilation.Results Among 130 preterm infants,88 cases(66.7%)were detected with brain injury,which included 29 cases(33%)with mild brain injury(5 cases with IVH of grade Ⅰ,24 cases with IVH of grade Ⅱ)and 59 cases(67%)with severe brain injury(53 cases with IVH of grade Ⅲ,1 case with IVH of grade Ⅳ and 5 cases with PVL).Gestational age and birth weight were the fundamental factors of brain injury in premature infants.The smaller the gestational age and the lower the birth weight,the highter the brain injury rate.Resuscitation,hypoxia,the use of auxiliary ventilation were also important high risk factors of brain injury in preterm infants.All these high risk factors could influence the autoregulation of cerebral blood and trigger or aggravate brain injury of preterm infants.Conclusions Smaller gestational age,lower birth weight,resuscitation,hypoxia,the use of auxiliary ventilation were all the high risk factors of brain injury in premature infants,which could influence the parameters of cerebral blood dynamics by influencing cerebral blood autoregulation of preterm infants and lead to the occurrence of brain injury in premature.

Objective To explore the mechanism of HMGB1 and TLR4 in pancreatic tissue of rats with severe acute pancreatitis and the intervention effect of Ulinastatin .Methods The 54 SD rats were completely random divided into control group ,SAP group and Ulinastatin treatment group ,and each group was divided into three groups :6 ,12 h and 24 h groups (each group n=6) .In con‐trol group ,we turned the pancreatic tissue ,in SAP group ,the SAP model was made with 5% taurocholic acid ;and in the treatment group ,and intravenous injection of ulinastatin was conducted after the SAP model was successfully made .Then we observed the pancreatic tissue pathology in the three groups .The amylase in serum was detected by EPS‐G7 assay ,the HMGB1 in serum and pancreatic tissue was detected by ELISA assay ,the expression levels of HMGB1 and TLR4 in pancreatic tissue were detected by Envision two‐step immunoassay .Results Compared with control group ,the amylase of each time point in SAP group and treatment group were significantly higher ,and the pathology changed obviously (P<0 .05) ,and the SAP model was successfully made .The HMGB1 expression in pancreatic tissue and serum started increase at 6 h ,increased quickly at 12 h and maintained the increasing trend to 24 h in SAP group and it was significantly higher at the same time point compared with that of control group (P<0 .05);at the same time point ,the HMGB1 in treatment group was significantly lower than that of SAP group (P<0 .05);in SAP group , the expression of TLR4 in pancreatic tissue started increasing at 6 h ,reached its peak at 12 h and started decreasing at 24 h ,it was significantly higher than the control group at the same time point (P<0 .05) .At the same time point ,the TLR4 was significantly lower in the treatment group than SAP group (P<0 .05) .Conclusion The proinflammatory effect of HMGB1 in SAP rats pancre‐atic could be partly combine its receptor TLR4 and MyD88‐dependent pathway through implementation ,and the protecting mecha‐nism of Ulinastatin could be interrupt the HMGB1 and TLR4 signaling pathway in SAP rats pancreatic tissue .

Objective To assess the aorta elastic properties in the procession of atherosclerosis by ultra‐high frequency ultrasound ,and to detect the relationship between the aorta elastic properties and the atherosclerotic plaque burden .Methods Mice deficient for the apolipoprotein E (ApoE‐/‐) with high‐cholestrol diet were studied as an age‐dependent model of atherosclerosis .At 8 ,16 ,24 and 32 weeks of age , the blood pressure in the ascending aorta was measured by catheter ,and the aorta mechanical properties were assessed by measuring aortic elastic modulus of the ascending aorta with ultra‐high frequency ultrasound .The plaque burden was assessed by high‐frequency ultrasound and Masson′s trichrome stain , separately .Results Vessel thickness at the lesion‐prone sites of the lesser curvature of the aorta and the proximal brachiocephalic artery increased with age ,consistent with the Masson′s trichrome staining which showed age‐dependent worsening of atherosclerosis in the mice model .Elastic modulus of the aorta significantly increased from 8 to 32 weeks of age in E‐/‐mice .There was a statistically difference between any two groups .Conclusions With the progression of atherosclerosis and the increased plaque burden ,aorta mechanical properties deteriorated in Apo E‐/‐mice .Ultra‐high frequency ultrasound was a potential tool for assessment of plaque burden and aorta mechanical properties in mouse model .

The Epstein-Barr virus latent membrane protein 1 (LMP1) oncopro tein causes multiple cellular changes, including activation of the NF-κB trans cription factor. To elucidate its possible mechanism, the interaction between LM P1 and the tumor necrosis factor receptor associated factor (TRAF) molecules was detected by the immunoprecipitation-Western blotting assay. Results showed tha t LMP1 was co-precipitated with TRAF1,2,3 in the LMP1-HNE2 cell line. In the m eantime, κB reporter gene analysis revealed that over expression of TRAF1 or TR AF2 augmented LMP1-mediated NF-κB activation from LMP1, suprisingly, overexpr ession of either TRAF3 or an dominant negative TRAF3 inhibited the NF-κB activ ation, indicating that TRAF1 or TRAF2 is a positive modulator of LMP1-mediated NF-κB activation, whereas,TRAF3 is a negative modulator. Rather both CTAR1 (carboxy-terminal activating region 1) and CTAR2 domains of LMP1 can independently activate NF-κB by interacting with TRAF proteins. These data indicate that LMP1 interacts TRAF1,2,3 which are important for LMP1-mediated N F-κB activation, and further suggest that signaling from TRAFs may be involved in the progression to malignancy in cells of epithelial origin such as nasophar yngeal carcinoma (NPC).

Mild-symptom erectile dysfunction (MSED) is commonly seen in clinical practice, but receives inadequate attention from both the patients and clinicians. Increasing researches have indicated that MSED is associated with not only unhealthy living habits and psychological factors but also the early progression of endothelial, metabolic and endocrine diseases. The diagnosis and treatment of MSED should be based on the relevant guidelines, with consideration of both its specific and common features. The therapeutic principle is a combination of integrated and individual solutions aimed at the causes of the disease. Drug intervention should be initiated if psychological therapy fails. Negligence of MSED may affect the quality of life of the patients and their partners, and what's more, might delay the management of some other severe underlying diseases. Adequate attention to the early diagnosis and treatment for MSED is of great significance for a deeper insight into the etiology of ED, the prevention of potential cardiovascular and metabolic diseases, and the improvement of the overall health of males.
Attention ; Erectile Dysfunction ; diagnosis ; etiology ; therapy ; Humans ; Male ; Quality of Life

There is no a systemic performance metrics for clinical data management. While the CDMC in China starts to develop the quality metrics for clinical data management, it is essential to think over the performance and pursue metrics implementation of clinical data management in China. This article provides the basic concept, development and implementation of the performance metric in clinical data management.
China ; Clinical Trials as Topic ; standards ; Data Collection ; standards ; Information Storage and Retrieval ; standards