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.

Vasculogenic mimicry (VM) is a pattern of neoplasm cells,which achieve their blood supplements through deformation and simulating capillary channels.Cumulative studies show that the formation of VM in glioma have a close relation with the glioma stem cells.In addition,some molecules such as microRNA,epithelial cell kinase-A2,vascular endothelial cadherin,transforming growth factor-Jβ,vascular endothelial growth factor receptor-2 and galectin-1 play important roles in the forming process of vasculogenic mimicry.Recently,it is found that VM is associated with the poor prognosis of patients with glioma and anti angiogenesis drug efficacy.So the research on VM about the discovery,formation mechanism,prognostic impact and the clinical significance will provide an opportunity for diagnosis and therapy of glioma in early stage.

Objective To analyze the clinical characteristics and treatment of post - renal acute renal failure (ARF)induced by Ceftriaxone in children. Methods The clinical data of 7 cases of post - renal acute renal failure in children from June 2012 to June 2014 induced by Ceftriaxone were analyzed. According to the changes in urine volume, serum creatinine,blood urea nitrogen and serum potassium level,liquid therapy,retrograde ureteral catheterization (RUC)and peritoneal dialysis was performed by step sequential therapy respectively. Results Seven cases were given intravenous Ceftriaxone under the fluid loss state. Abdominal pain,sudden anuria or oliguria appeared in the children af-ter 2. 6 d on the average,B ultrasonography and CT scanning showed multiple calculus in the bilateral renal pelvis and ureteral calculi. Blood BUN was 15. 2 - 37. 9 mmol/ L[(23. 3 ± 8. 6)mmol/ L],and blood Cr was 180 - 636 μmol/ L [(378. 9 ± 148. 4)μmol/ L]. These indicators met the diagnostic criteria for acute renal failure. In 7 cases,2 cases (28. 6% )received fluid therapy of sodium bicarbonate alkalization and anisodamine spasmolytic,4 cases(57. 1% )re-ceived fluid therapy and RUC,and 1 case(14. 3% )underwent fluid therapy and RUC and peritoneal dialysis. All of 7 cases(100% )were alive. In the average 4. 4 days renal function of 7 cases was returned to normal,and urine volume and electrolyte were also restored. Conclusions Step sequential therapy including fluid therapy,RUC and peritoneal dialysis is effective with post - renal ARF in children induced by Ceftriaxone.

Objective To investigate the ultrasound features of gouty joints during acute and past attacks. Methods Clinical data and ultrasound features of joints during the acute and past attacks of gouty patients who were experiencing an acute attack were collected. The differences of ultrasound features between two episodes, as well as the relationship with clinical characteristics were analyzed. Results Sixty-four patients were enrolled with 21 (33%) patients at their first attack. The first metatarsophalangeal (MTP1) joints were most frequently involved, meanwhile, 9.4% patients had two or more joints attacked during one episode. The most prevalent feature was synovitis at the acute phase, followed by double contour (DC) sign (18 cases, 28%), bone erosion (12 cases, 19%) and tophi (10 cases, 16%), while 23 patients had two or more pathological changes. Whereas, the DC sign was found most in previously attacked joints (10 cases, 33%), followed by tophi (8 cases, 27%), bone erosion (7 cases, 23%) and synovitis (4 cases, 13.3%). No positive pathological changes were found in asymptomatic joints. Synovitis was more common in joints during their acute attacks (80% vs 13%, χ2=20.475, P<0.01), however, DC sign and tophi were more common in previous attacked joints (10% vs 33% and 0 vs 27%, χ2=3.892, 6.642, P<0.05, respectively). Both the DC sign and tophi were positively correlated with the disease duration. Conclusion Synovitis is the most prevalent feature in gouty joints during acute episodes; even bone erosion can be found at the first attack. The DC sign, tophi and bone erosion are common in past attacked joints. The prevalence of both DC sign and tophi are increased along with disease durations. Subclinical synovitis can be detected in a small past of joints which are not at acute attack.

Objective To establish a cellulose acetate membrane electrophoretic method for separating the exogenous sulfated poly mannuguluronicate(911) from glycosaminoglycans.Methods 911 both in urine and ultrafiltrated urine were extracted with cetylpyridinium chloride (CPC), and then separated by two step electrophoretic method with two different buffer solutions. Results The results indicated that 911 was thoroughly separated from endogenous CSC and DS with its average recovery in urine approximately at 70%. Furthermore, the lowest sensitivity for determination of 911 in aquatic solution was 100 ?g?L -1 , whereas that in urine 250 ?g?L -1 and in ultrafiltrated urine 500 ?g?L -1 . And most importantly 911 in rat's urine was detectable after it's oral administration at dose of 200mg?kg -1 . Conclusions It is the first time for us to conduct the existence of 911 in urine by two step electrophoretic method with two different buffer solutions, suggestive of the feasibility to determine 911 in urine even following it's oral administration.

Objective To investigate the expressions of EGFR,Her-2 and VEGF in cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma,as well as its clinic value of carcinogenesis,progression and metastasis in ccrvical squamous cell carcinoma.Methods EGFR,Her-2 and VEGF were evaluated by immunohistochemistry in tissues from normal cervix,CIN and squamous cell carcinoma.Results The expressions of EGFR,Her-2 and VEGF were negative in normal cervix.The positive rate of EGFR,Her-2 and VEGF in CIN tissues were 35.0 ％ (14/40),37.5 ％ (15/40),42.5 ％ (17/40),while in cervical carcinoma tissues were 70.0 ％ (35/50),78.0 ％ (39/50),76.0 ％ (38/50) respectively,which had statistical significance.There was relationship between the expressions of EGFR,Her-2,VEGF proteins with pathological grade andlymph node metastasis of squamous cell carcinoma.The expressions of Her-2 and VEGF correlated with the clinical stage of quamous cell carcinoma.Conclusion The expressions of EGFR,Her-2 and VEGF may be correlated with the occurrence,development and metastasis of cervical carcinoma.It may be used as an important marker to evaluate the malignant degree of cervical carcinoma and it can be helpful in the treatment of cervical carcinoma.

Objective To study the relationship and clinical significance of the serum level of Pro-gastrinreleasing peptide31-98 (ProGRP)and bronchoalveolar lavage fluid for small cell lung cancer of different TNM staging.Methods 96 cases of SCLC with definite pathohistological typing were divided into stage Ⅰ～Ⅱ SCLC group (n=30),stage ⅢSCLC group (n=31),stage IVSCLC group (n=35),and the benign cases (n=90)were taken as control.Using enzyme-linked immunoserbent assay ( ELISA),the serum levels of ProGRP and bronchoalveolar layage fluid of all patients were detected,meanwhile the neuronspecific enolase were served as controls.The relation between serum and bronchoalveolar lavage fluid ProGRP level and small cell lung cancer of different TNM staging was analyzed.Results The serum level of ProGRP in stage Ⅰ～Ⅱ SCLC group,stage Ⅲ SCLC group,stage Ⅳ SCLC group,and the benign group were (295.33±118.56),(421.13±196.66),(758.76±326.19)and (29.68±16.32)μg/mol,respectively (P＜0.01 ).The level in bronchoalveolar lavage fluid ProGRP were ( 516.67 ±208.45),( 1170.55±414.65 ),( 1739.12±696.08 )and (49.23±22.50)μg/mol,respectively (P＜0.01 ).The serum level of NSE in stage Ⅰ～Ⅱ SCLC group,stage Ⅲ SCLC group,stage Ⅳ SCLC group,and the benign group were (10.36±6.76),(24.19±10.88 ),(35.76±17.30)and (9.70 ±5.28)mg/mol.The level in bronchoalveolar lavage fluid NSE were (16.66±11.62),(45.47±20.74),(65.18±29.87)and (9.70±5.28)mg/mol,respectively (P＜0.01).The positive rate of serum ProGRP in stage Ⅰ～Ⅱ SCLC group,stage Ⅲ SCLC group,stage Ⅳ SCLC group,and the benign group were 0.6000,0.7097,0.8286 and 0.0667 ,respectively(P＜0.01).The positive rate in bronchoalveolar lavage fluid ProGRP were 0.6333,0.7419,0.8571 and 0.0444,respectively (P＜0.01).The positive rate of serum NSE in stage Ⅰ～Ⅱ SCLC group,stage Ⅲ SCLC group ,stage Ⅳ SCLC group,and the benign group were 0.2333,0.6774,0.8000 and 0.2222.The positive rate in bronchoalveolar lavage fluid NSE were 0.2667,0.7097,0.8286 and 0.2667 ,respectively(P＜0.01 ).Both the ProGRP level and positive rate in serum and bronchoalveolar lavage fluid were obviously higher in stage Ⅰ～Ⅱ,Ⅲ,and Ⅳ SCLC group than in benign group (P＜0.01 ),both the ProGRP and NSE level and positive rate in bronchoalveolar lavage fluid were obviously higher than that in the serum.The positive rate in serum and bronchoalveolar lavage fluid ProGRP in stage Ⅰ～Ⅱ SCLC group were obviously higher than that in the NSE (P＜0.01),but there was no significant difference in stage Ⅲ and Ⅳ SCLC group.Conclusion ProGRP level in serum and bronchoalveolar lavage fluid have great value to the diagnosis and clinical stages of SCLC,especially the early diagnosis,ProGRP is better than NSE;As to the diagnosis of small cell lung cancer of different TNM staging,ProGRP detection in bronchoalveolar lavage fluid is better than in serum.

Objective To explore liver protective effects of the stems and leaves and roots of Scutellariae Radix from different areas of Gansu Province;To discuss differences in liver protection of the stems and leaves and roots of Scutellariae Radix. Methods All Kunming mice were randomly divided into 11 groups:normal group, model group, positive control group, Scutellariae Radix root groups and Scutellariae Radix stem-leaf groups of Longxi, Minxian, Weiyuan, Zhangxian. The mice received gavage with relevant medicine once a day for 7 days. 2 hours after the last medication, the mice were given peritoneal injection with 0.1%CCl4 and olive oil to establish the models with liver injury. Hepatic index, the activity of serum ALT and AST, the levels of T-AOC in the liver tissue were calculated in 18 hours after establishing the models. Results Compared with the model group, hepatic index, the activity of serum ALT and AST in the mice of Scutellariae Radix root groups from difference producing areas decreased significantly (P<0.05);the levels of T-AOC in the liver tissue was raised notably (P<0.05). Compared with stem-leaf groups from the same producing area, hepatic index, the activity of ALT and AST in the mice of Scutellariae Radix root groups were remarkably lower than these of Scutellariae Radix stem-leaf groups (P<0.05);the levels of T-AOC in the liver tissue was evidently higher than that of Scutellariae Radix stem-leaf group (P<0.05). Conclusion Scutellariae Radix root water decoction can prevent and protect CCl4-induced acute liver injury to a certain degree, while Scutellariae Radix stem-leaf water decoction shows no significant protective effect on acute liver injury.

Objective:To find the correlation of wrist bone mineral density ( BMD ) to wrist synovitis and erosion , by comparing wrist BMD and ultrasonography .Methods: A number of 80 female RA pa-tients were examined by BMD measurement of the femoral neck , spine and non-dominant wrist using du-al-energy X-ray absorptiometry ( DXA ) .Synovitis of the wrist was examined by ultrasonography .The wrist joint ( radiocarpal joint , dorsal midline , and carpoulnar joint ) was assessed in the same side of DXA, with transverse and longitudinal scans for USGS synovial hypertrophy and proliferation , tenosynovi-tis,tendinitis and bone erosion .Colour and power doppler ultrasonography ( PDUS) were used to sum the synovitis score .Results:We found:( 1 ) In the study , 80 female RA patients were enrolled , the mean age was 54.6 ±13.3 (27.0-80.0) years, the disease duration was 48 (12-116) months, and the body Mass Index was 23.0 ±4.0 (14.8-31.2) kg/m2 .The Wrist BMD ( g/cm2 ) in RA significantly reduced, compared with normal controls (0.297 ±0.121 vs.0.420 ±0.180,P<0.01).(2) The Wrist BMD (g/cm2) exceeded in early RA compared with the established RA (0.326 ±0.103 vs.0.285 ± 0 .132 ,P<0 .01 );the positive rate of severe osteoporosis in wrist was lower in early RA compared with the established RA(47.8%vs.64.9%, P<0.05); the positive rate of bone erosion in wrist by ultra-sound was lower in early RA compared with the established RA (39.1%vs.56.1%, P<0.01).(3) The wrist BMD ( g/cm2 ) in RA with high disease activity reduced compared with moderate and low disease activity (0.267 ±0.140 vs.0.280 ±0.126) and (0.267 ±0.140 vs.0.320 ±0.103) respec-tively , P<0 .05 ) .The percentages of positive ACPA in the high and moderate disease activity groups were significantly higher than those in the remission group (85% vs.81.8% and 92.6% vs.81.8%, respectively).DAS28ESR was correlated with wrist BMD (r=-0.288, P<0.01).(4) A significant positive correlation was found between wrist and spine /femur BMD ( r=0.634, P<0.01, r=0.795, P<0.01), and a negative correlation between wrist and disease duration and DAS 28ESR (r=-0.286, r=-0.301,P<0.01).There was a highly significant positive correlation between wrist BMD and femur BMD (r=0.95,P<0.05).(5) RA patients in wrist osteoporosis group had higher RF positive rate and ACPA rate than wrist osteopenia group (75.5%vs.55.6%,P<0.05,100% vs.83.3%, P<0.05). The patients of BMD osteoporosis group had higher DAS 28ESR compared with osteopenia group (5.3 ± 1.8 vs.3.7 ±1.5, P<0.01).The percentages of synovitis (61.5%vs.51.7%, P<0.05), tendeni-tis (14.3%vs.10.0%, P<0.05) and bone erosion (54.2%vs.46.2%, P<0.05) in wrist by ultra-sonography in osteoporosis group were higher than those of osteopenia group .(6) The wrist BMD in ne-gative bone erosion group by ultrasonography was lower than that in positive bone erosion group [ (0.333 ± 0.107) g/cm2 vs.(0.264 ±0.125) g/cm2, P<0.01], also the PDUS score was higher than positive bone erosion group (4.53 ±1.40 vs.2.55 ±2.66,P<0.01).Compared with negative bone erosion group, the patients in positive bone erosion group had longer disease duration (96.0 ±104.7) months vs.(66.2 ±78.0) months, P<0.05), higher percentage of RF (81.0% vs.53.8%,P<0.01), ACPA (92.7%vs.79.5%, P<0.05).and higher DAS28ESR (5.4 ±1.8 vs.4.2 ±2.0,P<0.05). The percentage of wrist synovitis in positive bone erosion group was higher (75.6% vs.30.8%,P<0.01) than that of negative bone erosion group , and moreover , the percentage of severe osteoporosis in the wrist was significantly higher (75.0%vs.46.4%, P<0.01).(7) A stepwise multivariate linear regression model was constructed to explore the relationship between the different clinical factors studied and a low wrist BMD.Statistically significant variables were age (P=0.001), disease duration (P=0.017), DAS28ESR (P=0.021), and ACPA (P=0.05).Conclusion:This study shows a highly sig-nificant correlation between hand BMD with disease duration and disease activity , and female RA patients with high titer of ACPA have lower wrist BMD .ABSTRACT Objective:To find the correlation of wrist bone mineral density ( BMD ) to wrist synovitis and erosion , by comparing wrist BMD and ultrasonography .Methods: A number of 80 female RA pa-tients were examined by BMD measurement of the femoral neck , spine and non-dominant wrist using du-al-energy X-ray absorptiometry ( DXA ) .Synovitis of the wrist was examined by ultrasonography .The wrist joint ( radiocarpal joint , dorsal midline , and carpoulnar joint ) was assessed in the same side of DXA, with transverse and longitudinal scans for USGS synovial hypertrophy and proliferation , tenosynovi-tis,tendinitis and bone erosion .Colour and power doppler ultrasonography ( PDUS) were used to sum the synovitis score .Results:We found:( 1 ) In the study , 80 female RA patients were enrolled , the mean age was 54.6 ±13.3 (27.0-80.0) years, the disease duration was 48 (12-116) months, and the body Mass Index was 23.0 ±4.0 (14.8-31.2) kg/m2 .The Wrist BMD ( g/cm2 ) in RA significantly reduced, compared with normal controls (0.297 ±0.121 vs.0.420 ±0.180,P<0.01).(2) The Wrist BMD (g/cm2) exceeded in early RA compared with the established RA (0.326 ±0.103 vs.0.285 ± 0 .132 ,P<0 .01 );the positive rate of severe osteoporosis in wrist was lower in early RA compared with the established RA(47.8%vs.64.9%, P<0.05); the positive rate of bone erosion in wrist by ultra-sound was lower in early RA compared with the established RA (39.1%vs.56.1%, P<0.01).(3) The wrist BMD ( g/cm2 ) in RA with high disease activity reduced compared with moderate and low disease activity (0.267 ±0.140 vs.0.280 ±0.126) and (0.267 ±0.140 vs.0.320 ±0.103) respec-tively , P<0 .05 ) .The percentages of positive ACPA in the high and moderate disease activity groups were significantly higher than those in the remission group (85% vs.81.8% and 92.6% vs.81.8%, respectively).DAS28ESR was correlated with wrist BMD (r=-0.288, P<0.01).(4) A significant positive correlation was found between wrist and spine /femur BMD ( r=0.634, P<0.01, r=0.795, P<0.01), and a negative correlation between wrist and disease duration and DAS 28ESR (r=-0.286, r=-0.301,P<0.01).There was a highly significant positive correlation between wrist BMD and femur BMD (r=0.95,P<0.05).(5) RA patients in wrist osteoporosis group had higher RF positive rate and ACPA rate than wrist osteopenia group (75.5%vs.55.6%,P<0.05,100% vs.83.3%, P<0.05). The patients of BMD osteoporosis group had higher DAS 28ESR compared with osteopenia group (5.3 ± 1.8 vs.3.7 ±1.5, P<0.01).The percentages of synovitis (61.5%vs.51.7%, P<0.05), tendeni-tis (14.3%vs.10.0%, P<0.05) and bone erosion (54.2%vs.46.2%, P<0.05) in wrist by ultra-sonography in osteoporosis group were higher than those of osteopenia group .(6) The wrist BMD in ne-gative bone erosion group by ultrasonography was lower than that in positive bone erosion group [ (0.333 ± 0.107) g/cm2 vs.(0.264 ±0.125) g/cm2, P<0.01], also the PDUS score was higher than positive bone erosion group (4.53 ±1.40 vs.2.55 ±2.66,P<0.01).Compared with negative bone erosion group, the patients in positive bone erosion group had longer disease duration (96.0 ±104.7) months vs.(66.2 ±78.0) months, P<0.05), higher percentage of RF (81.0% vs.53.8%,P<0.01), ACPA (92.7%vs.79.5%, P<0.05).and higher DAS28ESR (5.4 ±1.8 vs.4.2 ±2.0,P<0.05). The percentage of wrist synovitis in positive bone erosion group was higher (75.6% vs.30.8%,P<0.01) than that of negative bone erosion group , and moreover , the percentage of severe osteoporosis in the wrist was significantly higher (75.0%vs.46.4%, P<0.01).(7) A stepwise multivariate linear regression model was constructed to explore the relationship between the different clinical factors studied and a low wrist BMD.Statistically significant variables were age (P=0.001), disease duration (P=0.017), DAS28ESR (P=0.021), and ACPA (P=0.05).Conclusion:This study shows a highly sig-nificant correlation between hand BMD with disease duration and disease activity , and female RA patients with high titer of ACPA have lower wrist BMD .

Objective To investigate the musculoskeletal ultrasound (MSUS) findings in Chinese knee osteoarthritis (OA) patients.Methods All the MSUS data were from the outpatients with knee OA who visited Department of Rheumatology and Clinical Immunology,Peking University First Hospital from February 2013 to August 2014.MSUS findings included number and position of osteophyte,synovitis,thickness of cartilage,and so on.Comparisons between groups were made using t test,Chi-square tests.Results Six hundreds and seventy-four patients were included.Almost all the patients (96.1％) had osteophytes,most patients had both knees osteophytes.The most common osteophyte location was femoral (85.2％),followed by tibia and the upper edge of patella.The number of osteophytes differed from none to ten,and the distribution of bilateral knee osteophytes was symmetrical in most patients.There was no significant difference in the number of osteophytes between male and female,and patients over 60 years old had more osteophytes than the patients aged 60 or below.In all bursae lesions,the suprapatellar bursa were the most commonly affected [effusion,279 (41.4％),synovial hyperplasia,189(28.0％),synovitis 24 (3.6％)].There was no significant difference in the cartilage thickness between bilateral knees.But the cartilage thickness of female patients was significantly thinner than that of men [left:(2.0±0.5) mm vs (2.5:1:0.8) mm,t=3.859,P＜0.05;right:(2.0:1:0.5) mm vs (2.5±0.8) mam,t=4.109,P＜0.05],and the patients over 60 years old had thinner cartilage than patients younger than 60 years old [left:(2.0±0.6) mm vs (2.2±0.6) mm,t=2.108,P＜0.05;right:(2.0±0.6) mm vs (2.2±0.6) mm,t=2.507,P＜ 0.05].None patient had Calcium pyrophosphate dehydrate (CPPD) deposition in the cartilage.Conclusion In the ultrasonographic findings of knee OA in China,osteophyte could be found in 96％ patients,the most common location of osteophyte is the femur area.The distribution of bilateral knee osteophytes is symmetrical in most patients.Patients over 60 years old have more osteophytes.Nearly haff patients have joint effusion,one third patients have synovial hyperplasia or synovitis.Bilateral knee cartilage degeneration is symmetrical.Women and patients over 60 years old have thinner cartilage.