To study the protective effect and the mechanism of asiatic acid (AA) from Potentilla chinensis on alcohol hepatic injury in rats. Male Wistar rats were randomly divided into six groups: the normal control group, the AA control group (8 mg · kg(-1) AA), the model group (5.0-9.0 g · kg(-1) alcohol) and high, medium and low-dose AA-treated groups (alcohol + 8, 4, 2 mg · kg(-1) AA). Each group was orally administered with the corresponding drugs once a day for 24 weeks. Approximately 1. 5 hours after the final administration, all rats were killed, and their blood samples and hepatic tissues were collected. The AST and ALT in rat serum and the contents of MPO, TNF-α, IL-1β, SOD, GSH-Px, GSH-Rd and MDA in hepatic tissues were detected. The expressions of NF-κB, TLR4, CD14, MyD88, TRIF and protein expression in hepatic tissues were measured by western blot. The pathological changes in liver tissues were observed by histological examination. The results showed that compared with the model group, the AA-treated groups showed significant decreases in serum ALT, AST and MDA and increases in the activities of SOD, GSH-Px, GSH-Rd and MPO. Moreover, AA markedly inhibited the expressions of TNF-α, IL-1β, TLR4, CD14, MyD88 and NF-κB. The histological examination showed alleviated hepatic issue ijury to varying degrees. In short, asiatic acid (AA) from P. chinensis could protect alcohol-induced hepatic injury in rats. Its mechanism may be related to the inhibition of NF-κB inactivation and the reduction of inflammatory response.
Animals ; Liver ; drug effects ; pathology ; Liver Diseases, Alcoholic ; prevention & control ; Male ; NF-kappa B ; physiology ; Pentacyclic Triterpenes ; pharmacology ; Potentilla ; chemistry ; Protective Agents ; pharmacology ; Rats ; Rats, Wistar ; Toll-Like Receptor 4 ; antagonists & inhibitors

Objective To analyze the clinical data of patients with post-hepatectomy haemorrhage (PHH) and to discuss the treatment strategies.Method The clinicopathologic data of patients with PHH between 2005-2014 in the HPB Surgery Ward I,Peking University Cancer Hospital,were studied retrospectively.Results In the study period of 10 years,25 of 1 548 patients who underwent hepatectomy suffered from PHH,and 76％ (19/25) of these patients had underlying liver diseases.The common surgical operations followed by PHH were right hemihepatectomy (11/25),and segment Ⅶ/Ⅷ resection (8/25).The median time for PHH to be diagnosed was 27 h,and the median time from diagnosis of postoperative bleeding to reoperation or intervention was 3.5 h.Using the classification of PHH by the International Study Group of Liver Surgery (ISGLS),there were 1 patient in grade A,16 patients in grade B,and 8 patients in grade C.The perioperative mortality of PHH was 8％ (2/25).The most common bleeding site was from the hepatic artery.Conclusions PHH is a serious complication after liver resection,with low occurrence but high mortality.Most patients with PHH can be managed by conservative treatment.Emergency reoperation is required when instability in vital signs appears.Careful evaluation before operation,strict hemostasis during operation,and close monitoring after operation can effectively reduce the incidence and mortality of PHH.

Objective To evaluate the correlation between postoperative complications and prognosis after radical hepatic resection for colorectal liver metastasis (CRLM).Methods We retrospectively summarized patients' clinicopathological data and postoperative complications.Postoperative complications were graded using Dindo-Clavien system of classification.Then we investigate the relation between these data and prognosis.Results One hundred and seventy-three patients were recruited.Postoperative complications developed in 59 (34.1％) cases.37 patients had minor complications and 22 patients had major complications.On univariate (x2 =8.106,P =0.004) and multivariate analysis (x2 =8.006,P =0.005),complication was an independent predictor of overall survival (OS).However,in a subgroup of patients with minor compications,morbidity was not associated with a significant reduction in both OS (x2 =3.199,P =0.074) and disease-free survival (x2 =1.313,P =0.252).Conclusions Postoperative complications are an independent factor for long-term outcomes after hepatic resection for CRLM.

Objective Bisegmentectomy Ⅶ-Ⅷ can be an alternative option for the tumor localized in segments Ⅶ and Ⅷ and infiltrating the main trunk of RHV instead of a right hemihepatectomy.This study was to evaluate the safety and practicability of the removal of segments Ⅶ and Ⅷ of the liver with the resection of the main trunk of RHV without vascular reconstruction.Method 13 consecutive patients underwent bisegmentectomy Ⅶ-Ⅷ with the resection of the RHV between Nov.2006 and Dec.2012 at Beijing Cancer Hospital 1st Department.of HPB Surgery.Results Bisegmentectomy Ⅶ-Ⅷ with the resection of the RHV was performed in all 13 patients successfully without the distal vein reconstruction.The duration of the operations was 90-215 min.Mean blood loss was estimated to be 200 ml (100-700 ml).Indications for a bisegmentectomy Ⅶ-Ⅷ included hepatocellular carcinoma in 6 cases,intrahepatic cholangiocarcinoma in one,liver metastasis in 4 and hepatic hemangioma in 2 as confirmed pathologically.All patients recovered without severe complications.The atrophy of segment Ⅵ due to the venous drainage obstacle was observed in 3 patients without the dysfunction of liver postoperatively.Conclusions It is safe and practicable to perform Ⅶ and Ⅷ bisegmentectomy with resection of the right hepatic vein without vascular reconstruction for liver tumors.

Objective To study the survival outcome and the survival-related factors in patients who received liver resection for multiple (≥4) liver metastases of colorectal cancer.Method The results for patients who received partial hepatectomy for four or more colorectal hepatic metastases carried out in the 1 st Department of HPB Surgery,Peking University Cancer Hospital were studied retrospectively.Results Between 2002 and 2013,of 239 patients,60 patients with four or more colorectal hepatic metastases received partial hepatectomy.The median overall survival was 35.2 months and the 5-year survival was 28.2％ (17/60).There were two actuarial 5-year survivors.The median disease-free survival was 6.9 months,with 1 actuarial disease-free survivor at 5 years.There were no perioperative deaths,and the perioperative morbidity was 36.7％ (22/60).Major (hemi-liver or more) liver resection and 7 or more metastases were independently associated with poor survival outcome.Perineural Invasion (T4) of the primary tumor,size of the largest metastasis (≥4 cm),neoadjuvant chemotherapy,and resection of recurrent disease were also associated with survival outcome.Conclusions Long-term survival could be achieved after resection of multiple colorectal liver metastases.Minor resection for multiple colorectal metastases was superior in survival compared with major resection.Additional survival advantage could be achieved by resection of recurrent disease.

Objective To investigate survival for primary duodenal carcinoma patients after radical resection and identify risk factors associated with overall survival.Methods Data of 51 patients with primary duodenal carcinomas who underwent radical resection between December 2003 and December 2012 at Beijing Cancer Hospital were included.Survival analysis was drawn by Kaplan-Meier method,univariate and multivariate analyses were performed to identify variables associated with survival after resection by COX regression model.Results The median overall survival time was 67 months,and the median disease-free time was 40 months,1-,2-and 3-year overall survival rates were 88％,84％ and 67％,respectively.Multivariate analysis revealed that regional lymph-node positive (P =0.032) and CA199 ＞ 37 U/ml (P =0.037) were independent risk factors of patients' overall survival.Conclusions Radical resection improves survival for primary duodenal carcinoma patients.Regional lymph-node positive and CA199 ＞37 U/ml were the most important risk factors of patients'overall survival.

Objective To identify the risk factors associated with overall survival (OS) for patients undergoing partial hepatectomy for colorectal liver metastases,and to assess the predictive values of five published scoring systems in an independent patient cohort for the purpose of external validation.Methods The clinical,pathologic,and complete follow-up data were prospectively collected from 303 consecutive patients who underwent primary hepatic resection for colorectal liver metastases at the Beijing Cancer Hospital from January 2000 to Aug 2014.The predictive values of the Nordlinger score,the Memorial Sloan-Kettering Cancer Center (MSKCC) score,the Iwatsuki score,the Basingstoke index,and the Konopke scoring system were assessed in this patient set.The clinical and pathologic parameters were further analyzed using univariate and multivariate analyses.Results The 1-,3-and 5-year overall survival were 89.2％,50.8％ and 38.6％,respectively.The median survival time was 37 months.Two risk factors were found to be independent predictors of poor overall survival:the N stage of the primary tumor,and a carcinoembyonic antigen level ＞ 30 μg/L.The MSKCC score had the best independent predictive power for survival when compared with the other 4 prognostic systems (C-index:0.903).Conclusion In our patient cohort,the MSKCC score was the best staging system in predicting survival.

Objective:To compare the safety and long-term survival of patients with synchronous rectal cancer liver metastasis, who received either simultaneous or staged resection to treat primary tumor and liver metastases. Methods:Clinicopathologic and peri-operative data were collected retrospectively from 54 patients with synchronous rectal cancer liver metastasis, who received both prima-ry and liver resections between January 2000 and April 2015 at Peking University Cancer Hospital. Routine follow-up was conducted. The safety and long-term survival of 19 patients who underwent simultaneous resection were compared with those of 35 patients who received staged resection. Results:The clinicopathologic data between the two groups were comparable. Postoperative Clavien-Dindo grades 1, 2, 3, and 4 complications were 10.5%(2/19), 31.6%(6/19), 5.3%(1/19), and 10.5%(2/19) for the simultaneous group, respec-tively, and 8.6%(3/35), 17.1%(6/35), 25.7%(9/35), and 0%(0/35) for the staged group correspondingly, which were not significantly different (P=0.093). However, the median postoperative hospital stay of the simultaneous group was significantly shorter than that of the staged group (14 days versus 25 days, P<0.001). The median postoperative overall survival (OS) and disease-free survival (DFS) be-tween these groups were not significantly different [not reached versus 39 months for OS, respectively (P=0.649);10 months versus 10 months for DFS, respectively (P=0.827)]. Conclusion:The postoperative complications in simultaneous resection group were not sig-nificantly increased compared with those in staged resection group for synchronous rectal cancer liver metastasis. The long-term results among the groups were similar.

OBJECTIVETo clarify the effects of nylestriol on microarchitecture and interleukin-6 (IL-6) mRNA expression in tibial bone in ovariectomized rats.

METHODS30 female rats were randomly allocated into 3 groups: sham, OVX and nylestriol-treated group. Nylestriol-treated group were ovariectomized, then fed with nylestriol for 3 months and the bone mineral density (BMD) was measured in lumbar vertebra by dual energy x-ray absorptiometry. After sacrifice of the animal, bone histomorphometric parameters were measured to study the changes in bone microarchitecture, and RT-PCR was performed to detect the expression of IL-6 mRNA in bone tissue.

RESULTSBMD was significantly reduced, while IL-6 mRNA level elevated in the OVX group compared with the sham group. Static histomorphometric data showed that the trabecular bone volume, mean trabecular plate thickness and density were reduced while the mean trabecular plate space elevated remarkably in the OVX group in comparison with that in the sham group. As for dynamic parameters, trabecular osteoid surface, tetracyclin labeled surface and bone turnover rate were increased while osteoid maturation rate decreased significantly in the OVX group compared with the sham group. BMD, IL-6 mRNA expression and bone histomorphometric parameters were improved in nylestriol-treated rats.

CONCLUSIONNylestriol plays an important role in maintaining bone volume and improving bone microarchitecture by markedly inhibiting bone turnover and bone resorption, which might be to some degree attributed to reduced IL-6 expression.

Animals ; Bone Remodeling ; drug effects ; Bone Resorption ; prevention & control ; Estradiol Congeners ; pharmacology ; therapeutic use ; Female ; Interleukin-6 ; biosynthesis ; genetics ; Osteoporosis ; drug therapy ; etiology ; pathology ; Ovariectomy ; Quinestrol ; analogs & derivatives ; pharmacology ; therapeutic use ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Wistar ; Tibia ; pathology

OBJECTIVETo study the role of PAK6 in prostate cancer by cloning PAK6-N terminal sequence into E.coli and preparing its polyclonal rabbit antibody to detect PAK6 expression in prostate cancer.

METHODSBased on human PAK6 cDNA sequence, we designed a pair of primers to amplify the PAK6-N terminal sequence by PCR. The PCR product was subcloned into the bacterial expression vector pGEX-4T-1 via EcoRI/XhoI sites, and the recombinant plasmids were identified by enzymatic cleavage followed by DNA sequence analysis. By transforming the expression vector into component E.coli BL21 cells, the GST-PAK6-N fusion protein was expressed with IPTG induction. Glutathione-Sepharose beads were used to purify GST- PAK6-N fusion protein. Anti-PAK6 polyclonal antibody was produced by immunizing rabbits with purified GST-PAK6 N-terminal fusion protein. Anti-PAK6 polyclonal antibody was purified by protein A beads and used for detection of PAK6 expression in 3 prostate cancer specimens.

RESULTS AND CONCLUSIONWe cloned PAK6-N terminal gene fragment successfully, purified GST-PAK6 N-terminal fusion protein, and obtained polyclonal rabbit PAK6 antibody. Immunohistochemistry indicated that PAK6 expressed in the stroma instead of the cancer cells in prostate cancer. All of the 3 prostate cancer specimens showed positive staining in the stroma, suggesting that PAK6 may participate in the stroma-cancer cell interaction in prostate cancer.

Aged ; Animals ; Antibodies, Monoclonal ; immunology ; isolation & purification ; Cloning, Molecular ; DNA, Complementary ; chemistry ; genetics ; Electrophoresis, Polyacrylamide Gel ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Male ; Polymerase Chain Reaction ; Prostatic Neoplasms ; enzymology ; genetics ; Rabbits ; Recombinant Fusion Proteins ; immunology ; metabolism ; Sequence Analysis, DNA ; p21-Activated Kinases ; genetics ; immunology ; metabolism