The systematic treatment based on gemcitabine plus cisplatin is recommended as the current standard chemotherapy for unresectable or metastatic biliary tract cancers.However,the exact benefits from the recognized regime are still dismal.We thus elicit this study in an attempt to analyze whether targeted therapy coupled with various chemotherapy could produce improvement of survival benefits.The clinical trials were searched electronically from databases till July 2016 published in English and Chinese.Nine hundred and sixty-four patients from 7 trials were identified in our analysis.The overall analysis achieved a significantly higher overall response rate (ORR) among the patients treated with targeted drugs plus chemotherapy than chemotherapy alone (OR=1.87;95％ CI:1.37-2.57;P=0.000),but failed in the overall progression-free survival (PFS) [mean difference (MD)=0.63;95％ CI:-0.45-1.72;P=0.26] and overall survival (OS) (MD=-0.67;95％ CI:-2.54-1.20;P=0.49).In the sub analysis,better ORR was obtained with the addition of EGFR (OR=1.75;95％ CI:1.20-2.56;P=0.004) and VEGFR (OR=2.5;95％ CI:1.28-4.87;P=0.007) targeted therapy.Furthermore,the sub analysis of EGFR target showed an significant improvement on PFS (MD=l.36;95％ CI:0.29-2.43;P=0.01).No significant differences were observed in the incidences ofneutropenia (OR=1.37;95％ CI:0.89-2.12),thrombocytopenia (OR=l.40;95％ CI:0.83-2.39),anemia (OR=l.21;95％ CI:0.62-2.38),peripheral neuropathy (OR=1.52;95％ CI:0.81-2.88),increased AST/ALT (OR=l.40;95％ CI:0.82-2.39) as well as fatigue (OR=1.65;95％ CI:0.96-2.84) in either of the treatment groups.In conclusion,better ORR associated with chemotherapy combined with targeted therapy (both targeting EGFR and VEGF) is found in the present mcta-analysis without the cost of increased unacceptable toxicities,but regretfully not for the OS.The sub-analysis of targeting EGFR instead of VEGF obtains a superior PFS.Otherwise,there is no statistically significant difference in the overall PFS between the combination regime and chemotherapy alone.Given the paucity of favorable data,we need further studies to characterize optimal targeted agents to confirm the potential value to biliary tract cancer.

AIM To study the chemical constituents from the roots tuber of Aconitum ouvrardianum H..METHODS The ethyl acetate fraction of methy extract from A.ouvrardianum roots tuber was isolated and purified by silica,aluminium oxide column,Sephadex LH-20,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Eighteen compounds were isolated and identified as kongboendine (1),anisoezochasmaconitine (2),lipo-14-O-anisoylbikhaconine (3),franchetine (4),talatisamine (5),chasmanine (6),crassicauline A (7),chasmaconitine (8),14-dehydrotalatisamine (9),lipoindaconitine (10),indaconitine (11),yunaconitine (12),lipoyunaconitine (13),liljestrandisine (14),transconitine B (15),ouvrardiantine (16),atropurpursine (17),8-deacetylyunaconitine (18).CONCLUSION Compounds 1-4,9-10,13,15,17 are isolated from this plant for the first time.

OBJECTIVETo evaluate the safety, effectiveness, and outcomes of holmium laser enucleation of the prostate (HoLEP) for patients with symptomatic enlarged prostate after 11 years of experience.

METHODSThe 3162 evaluable patients treated with holmium laser enucleation of the prostate at our institution between August 2001 and August 2011 were retrospectively analyzed. Study variables included International Prostate Symptom Score, quality of life, maximum urinary flow rate, and incidence of complications.

RESULTSHoLEP were performed successfully completed, not patients which occurs as electric cutting syndrome. The operation time was (60.8 ± 18.4) minutes; average resection of prostate quality was (45.4 ± 24.4) g. The hemoglobin reduce though surgery was (1.81 ± 0.93) g/L; percentage of red blood cell change was 1.24% ± 0.43%, and sodium blood drop was (1.14 ± 0.35) mmol/L. Postoperative patients of hospital stay (3.1 ± 1.1) days, average time of indwelling catheter time was (2.3 ± 0.8) days. Patients were followed up for 6-131 months time, an average of 32.4 months. Postoperative patients with international prostate symptom score progressive declined. The quality of life score was 2.2 ± 1.7, and it less than preoperative (5.7 ± 3.3, t = 2.447, P < 0.01). The time of follow-up droped further, and postoperative comparative differences have statistical significance (t = 2.179, 2.228, 2.306 and 2.365, P < 0.05). The maximum urinary flow rate also improved (P < 0.05). Postoperative complications included bladder neck contracture (4 cases), urinary tract infection (107 cases), urethral stricture (11 cases) and urinary incontinence (11 cases). The 11 patients reoperation.

CONCLUSIONSHoLEP treatment of benign prostatic hyperplasia could achieve the advantages of open surgery the same effect. It had fewer damage, faster recovery, fewer complications, and is a good treatment option.

Adult ; Aged ; Aged, 80 and over ; Humans ; Lasers, Solid-State ; Male ; Middle Aged ; Prostatic Hyperplasia ; surgery ; Retrospective Studies ; Transurethral Resection of Prostate ; Treatment Outcome

OBJECTIVETo establish an animal model of congenital heart defect with decreased pulmonary blood flow for better understanding the pathophysiology of pulmonary vascular development and related regulatory mechanisms of congenital heart defect with decreased pulmonary blood flow.

METHODOne to two months old pigs were randomly divided into three groups: control group (group C, n = 6) with right chest small incisions induced transient pulmonary blood reduction; light-moderate stenosis groups (group T(1), n = 7): artificial atrial septum defect (ASD) plus controlled pulmonary artery banding to generate a systolic pressure gradient of 20 - 30 mm Hg (1 mm Hg = 0.133 kPa); severe stenosis groups (group T(2), n = 7): similar surgical procedures as group T(1), and controlled pulmonary artery banding to generate a systolic pressure gradient ≥ 30 - 50 mm Hg. 64-slice computed tomography scanning was performed at one month post operation. Arterial blood gas analysis, hemoglobin value, pulmonary vessel, ASD and banding ring diameters and trans-pulmonary artery banding pressure (Trans-PABP) were determined at two months post operation.

RESULTSOne pig died due to tracheal intubation accident in the C group, one pig died due to bowel obstruction in the T(1) group and two pigs died due to acute right heart failure and chronic heart failure respectively in T(2) group. 64-slice CT angiography results showed that aortic diameter of T(1) group was significantly lower than that of C group and banding diameter was significantly lower than aortic diameter in the T(1) and T(2) groups at one month post operation. Two months after operation, the size of ASD were (8.0 ± 0.5) mm and (8.9 ± 1.4) mm (P > 0.05) respectively in the T(1) and T(2) groups after operation. The Trans-PABP was significantly higher in the T(1) and T(2) groups than in C group (P < 0.01), and the Trans-PABP was significantly higher in the T(2) group than in T(1) group (P < 0.01). PaO2 and SaO2 in the T(1) and T(2) groups were significantly lower than those in C group.

CONCLUSIONArtificial atrial septum defect combined pulmonary artery banding procedures could be successfully used to establish model of congenital heart defect with decreased pulmonary blood flow and this model could help to understand the pathophysiology and monitor therapy efficacy for patients with congenital heart defect with decreased pulmonary blood flow.

Animals ; Disease Models, Animal ; Heart Defects, Congenital ; physiopathology ; Lung ; blood supply ; Pulmonary Artery ; physiopathology ; Pulmonary Circulation ; Pulmonary Veins ; physiopathology ; Swine

OBJECTIVETo study the possible role of JNK1, Raf-1 and Livin in the carcinogenesis of sporadic colorectal tubular adenoma.

METHODSImmunohistochemical staining was used to detect the expression of JNK1, Raf-1 and Livin proteins in 65 sporadic colorectal tubular adenomas with dysplasia of varying degrees and 22 colorectal tubular adenoma with cancerous area.

RESULTSIn normal colorectal mucosa, colorectal tubular adenoma with dysplasia and colorectal tubular adenoma with cancerous area, the positive rate of JNK1, Raf-1 and Livin expression was increased gradually. The positive expression of JNK1, Raf-1 and Livin was all significantly higher in the cases of colorectal tubular adenoma with dysplasia or with cancerous area than that in normal colorectal mucosa (P < 0.05), and the positive expression of JNK1, Raf-1 and Livin was significantly higher in colorectal tubular adenoma with cancerous area than that in colorectal tubular adenoma with dysplasia of different degrees (P < 0.05). In the cases of colorectal tubular adenoma with dysplasia of varying degrees, the positive expression of Raf-1 was increased along with the increasing dysplasia degree of colorectal tubular adenoma (P < 0.05). Coexpression of JNK1, Raf-1 and Livin increased gradually in the carcinogenesis of sporadic colorectal tubular adenoma, while positive correlation was found among the expressions of JNK1, Raf-1 and Livin.

CONCLUSIONJNK1, Raf-1 and Livin may be involved in the carcinogenesis of sporadic colorectal tubular adenoma.

Adaptor Proteins, Signal Transducing ; metabolism ; Adenoma ; metabolism ; pathology ; Adult ; Carcinoma ; metabolism ; pathology ; Cell Transformation, Neoplastic ; Colorectal Neoplasms ; metabolism ; pathology ; Female ; Humans ; Inhibitor of Apoptosis Proteins ; metabolism ; Intestinal Mucosa ; metabolism ; pathology ; Male ; Mitogen-Activated Protein Kinase 8 ; metabolism ; Neoplasm Proteins ; metabolism ; Precancerous Conditions ; metabolism ; pathology ; Proto-Oncogene Proteins c-raf ; metabolism

OBJECTIVETo investigate the in vitro effect of caffeic acid phenethyl ester (CAPE), a NF-κB inhibitor, on the apoptosis of osteoarthritic (OA) chondrocytes and on the regulation of the gelatinases matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9).

METHODSAnnexin V-FITC/propidium iodide (PI) labeling and western blotting were used to observe and determine the apoptosis in TNFα-stimulated primary cultured osteoarthritic chondrocytes. Also, gelatin zymography was applied to examine MMP-2 and MMP-9 activities in supernatants.

RESULTSIt was confirmed by both flow cytometry and western blotting that chondrocytes from OA patients have an apoptotic background. Use of CAPE in combination with 10 ng/mL of TNFα for 24 h facilitated the apoptosis. MMP-9 in the supernatant could be autoactivated (from proMMP-9 to active MMP-9), and the physiologic calcium concentration (2.5 mmol/L) could delay the autoactivation of MMP-9. The activities of MMP-2 and MMP-9 in the fresh supernatant increased significantly in response to stimulation by 10 ng/mL of TNFα for 24 h. The stimulatory effect of TNFα just on proMMP-9 was counteracted significantly by CAPE.

CONCLUSIONNF-κB could prevent chondrocytes apoptosis though its activation was attributed to the increase of proMMP-9 activity induced by TNFα (a pro-apoptotic factor). Therefore, therapeutic NF-κB inhibitor was a 'double-edged swords' to the apoptosis of chondrocytes and the secretion of MMP-9.

Aged ; Apoptosis ; drug effects ; Caffeic Acids ; pharmacology ; therapeutic use ; Calcium ; physiology ; Cells, Cultured ; Chondrocytes ; drug effects ; enzymology ; secretion ; Drug Evaluation, Preclinical ; Female ; Humans ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Middle Aged ; NF-kappa B ; antagonists & inhibitors ; Osteoarthritis ; drug therapy ; enzymology ; Phenylethyl Alcohol ; analogs & derivatives ; pharmacology ; therapeutic use ; Tumor Necrosis Factor-alpha ; pharmacology

OBJECTIVETo establish an ultra-high performance liquid chromatography coupled with triple quadrupole mass (UPLC-TQ-MS) for determination of four terpene lactones.

METHODChromatographic separation was carried out on a ACQUITY UPLC BEH C18 column (2.1 mm x 100 mm, 1.7 microm) with isocratic elution of 70% methanol at a flow rate of 0.4 mL x min(-1), the column temperature was set at 30 degrees C; Waters Xevo TQ worked in multiple reaction monitoring mode.

RESULTAll calibration curves were linear (r > 0.990 3) over the tested ranges. The average recoveries ranged from 98.83% to 103.9% with RSD value below 3.0%. The contents of total terpene lactones in Ginkgo biloba leaves were significantly different in different ages. The contents in the leaves of young ginkgo tree were higher than that in old tree.

CONCLUSIONThe method was simple and fast with high precision, sensitivity and repeatability, which can be used for qualitative and quantitative analysis of terpene lactones in G. biloba leaves.

Calibration ; Chromatography, High Pressure Liquid ; methods ; Ginkgo biloba ; chemistry ; Lactones ; analysis ; Mass Spectrometry ; methods ; Plant Leaves ; chemistry ; Reproducibility of Results ; Terpenes ; analysis ; Time Factors

BACKGROUNDIncreased blood pressure and elevated total cholesterol (TC) level are the two most important modifiable risk factors of cardiovascular disease (CVD) in the world. Hypertension and hypercholesterolemia co-exist more often than would be expected and whether there is a synergistic impact on fatal CVD between elevated TC and hypertension need to be further examined in Chinese population.

METHODSWe conducted a cohort study which recruited 5092 Chinese male steelworkers aged 18 - 74 years in 1974 - 1980 and followed up for an average of 20.84 years. Totally 302 fatal CVD events were documented by the year of 2001. Cox proportional hazards regression models were undertaken to adjust for baseline variables with fatal CVD events as the outcome variable. Additive interaction model was used to evaluate the interaction between elevated TC and hypertension.

RESULTSHypercholesterolemia and hypertension were significantly associated with an increased hazard ratio (HR) of fatal CVD (1.67 (95%CI 1.18 - 2.38) and 2.91 (95%CI 2.23 - 3.80) respectively. Compared to participants with normotension and TC < 240 mg/dl, the HRs were 1.11 (95%CI 0.56 - 2.21), 2.74 (95%CI 2.07 - 3.64) for hypercholesterolemia and hypertension respectively, and 5.51 (95%CI 3.58 - 8.46) for participants with both risk factors. There was an additive interaction with a 2.65 (95%CI 0.45 - 4.85) relative excess risk (RERI) between hypercholesterolemia and hypertension on CVD.

CONCLUSIONWe found that the risk of fatal CVD was significantly associated with an additive interaction due to hypercholesterolemia and hypertension besides a conventional main effect derived from either of them, which highlights that the prevention and treatment of both risk factors might improve the individual risk profile thus reduce the CVD mortality.

Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; Cardiovascular Diseases ; blood ; etiology ; mortality ; Cholesterol ; blood ; Humans ; Hypercholesterolemia ; blood ; complications ; Hypertension ; blood ; complications ; Male ; Middle Aged ; Steel ; Young Adult

OBJECTIVETo evaluate the major causes of death and risk factors among male steelworkers in Beijing.

METHODSThe study included 5137 men from the cohort of Beijing Capital Steel and Iron Company. The baseline survey was performed in 1974, 1979 and 1980 and the final follow-up evaluation was made in 2001 with a mean follow-up of 20.8 years. Causes of death were coded according to the Ninth Revision of International Classification of Diseases (ICD-9). The mortality was calculated by person-years of follow-up and age-standardized according to the 2000 census data in China. Cox proportional-hazards models adjusting for risk factors were used to estimate the relative risk of death.

RESULTSThere is 760 deaths during follow-up. Age-standardized mortality from all causes was 643.0 per 100,000 person-years. The three leading causes of death were malignant neoplasms (mortality, 231.3 per 100,000 person-years), cerebrovascular diseases (mortality, 139.3 per 100,000 person-years) and heart diseases (mortality, 96.4 per 100,000 person-years). The multivariate-adjusted relative risk of death and the population attributable risk proportion for risk factors were as follow: cigarette smoking (95% CI, 1.174 to 1.765); hypertension (95% CI, 1.370 to 1.904) and hypercholesterolemia (95% CI, 1.057 to 1.537).

CONCLUSIONSOur study indicates that malignant neoplasms, cerebrovascular diseases and heart diseases were major causes of death among male steelworkers. Furthermore, cigarette smoking, hypertension and hypercholesterolemia are leading preventable risk factors for death.

Adolescent ; Adult ; Aged ; Cardiovascular Diseases ; mortality ; Cause of Death ; China ; epidemiology ; Follow-Up Studies ; Humans ; Male ; Metallurgy ; Middle Aged ; Neoplasms ; mortality ; Proportional Hazards Models ; Prospective Studies ; Risk Factors ; Stroke ; mortality

OBJECTIVETotal cholesterol (TC) is an important risk factor for myocardial infarction (MI), but the effect of TC on MI in Chinese male hypertension population has not been well documented. We conducted a prospective cohort study to determine the incidence and relative risk for MI across a wide range of TC levels in Chinese male hypertension population.

METHODSA cohort of 5298 male employees aged 18-74 years recruited from Capital Steel and Iron Company in Beijing of China in 1974-1980 was followed up for an average of 20.84 years. A total of 122 incident MI cases were identified during the period of follow-up.

RESULTSThe incidence of MI among participants with elevated TC and those with desirable TC in male non-hypertension population was 137.20 and 63.81 per 100,000 person-years, respectively; and the corresponding incidence in male hypertension population was 279.80 and 130.96 per 100,000 person-years, respectively. After adjustment for important covariables, 10.38%, 16.71%, and 23.80% of MI cases were attributable to hypertension, elevated TC, and hypertension plus elevated TC, respectively. In male hypertension population, the multivariate adjusted hazard ratios of MI were 1.21, 2.39, 3.38, and 3.95 for participants with TC level of 5.17-5.68, 5.69-6.20, 6.21-6.71, and > or = 6.72 mmol/L, compared with those with TC < 5.17 mmol/L. The corresponding population attributable risks were 2.92%, 9.20%, 8.87%, and 9.84%, respectively.

CONCLUSIONElevated TC is an important independent risk factor of MI both in male non-hypertension and hypertension populations. There is a linear association between TC level and MI incidence in Chinese male hypertension population.

Adolescent ; Adult ; Aged ; China ; epidemiology ; Cholesterol ; blood ; Humans ; Hypertension ; blood ; complications ; epidemiology ; Incidence ; Longitudinal Studies ; Male ; Middle Aged ; Myocardial Infarction ; blood ; complications ; epidemiology ; Proportional Hazards Models ; Risk Factors ; Young Adult