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Objective To investigate the influence factors of tumor diameter and related prognostic factors on the prognosis of hilar cholangiocarcinoma.Methods The retrospective case-control study was conducted.The clinicopathological data of 240 patients who underwent resection of hilar cholangiocarcinoma in the West China Hospital of Sichuan University between January 1995 and January 2013 were collected,including 104 patients with tumor diameter ≤ 2 cm (8 with tumor diameter ≤ 1 cm and 96 with 1 cm ＜ tumor diameter ≤ 2 cm),85 with 2 cm ＜ tumor diameter ≤ 3 cm and 51 with tumor diameter ＞ 3 cm (40 with 3 cm ＜ tumor diameter ≤ 4 cm and 11 with tumor diameter ＞ 4 cm).Observation indicators:(1) surgical situations;(2) follow-up situations;(3) risk factors analysis affecting the prognosis of patients;(4) correlation analysis between related prognostic indicators and tumor diameter.The follow-up using outpatient examination and telephone interview was performed to detect the survival up to August 2016.The survival curve and survival rate were respectively drawn and calculated by the Kaplan-Meier method,and the Log-rank test was used for survival analysis.The prognostic factors and correlation between related prognostic indicators and tumor diameter were respectively analyzed using the COX proportional hazard model and logistic regression model.Results (1) Surgical situations:240 patients underwent successful resection of hilar cholangiocarcinoma and lymph node dissection.Of 73 patients with postoperative complications,1 died of intraperitoneal infection induced to systemic infection and multiple organ failure,1 diel of renal failure,and other patients were cured by symptomatic treatment.(2) Follow-up situations:240 patients were followed up for 12.0-98.0 months,with a median time of 47.4 months.The overall median survival time,1-,3-and 5-year overall survival rates were respectively 30.6 months,81％,47％ and 29％.The median survival time and 5-year survival rate were 46.5 months,34％ in patients with tumor diameter ≤ 2 cm and 30.5 months,30％ in patients with 2 cm ＜ tumor diameter ≤ 3 cm and 13.8 months,20％ in patients with tumor diameter ＞ 3 cm,respectively,with a statistically significant difference (x2 =17.83,P＜0.05).Results of further analysis showed the median survival time and 5-year survival rate were 31.3 months,38％ in patients with tumor diameter ≤ 1 cm and 46.5 months,34％ in patients with 1 cm ＜ tumor diameter ≤ 2 cm,respectively,with no statistically significant difference (x2=1.16,P＞O.05).The median survival time and 1-year survival rate were 14.7 months,62％ in patients with 3 cm ＜ tumor diameter ≤ 4 cm and 13.0 months,55％ in patients with tumor diameter ＞ 4 cm,respectively,with no statistically significant difference (x2 =2.34,P＞O.05).(3) Risk factors analysis affecting the prognosis of patients:univariate analysis showed that tumor diameter,surgical margin,lymph node metastasis,vascular invasion and histological differentiation were the related factors affecting patients' prognosis [hazard ratio (HR)=1.456,8.714,1.737,2.246,1.665;95％ confidence interval (C I):1.212-1.748,5.558-13.663,1.311-2.301,1.494-3.378,1.375-2.016,P ＜ 0.05].The multivariate analysis showed that 2 cm ＜ tumor diameter ≤ 3 cm,tumor diameter ＞ 3 cm,R1 resection,lymph node metastasis and low-differentiated tumor were the independent risk factors affecting poor prognosis of patients (HR =1.559,1.868,7.410,1.521,2.274,95％ CI:1.125-2.160,1.265-2.759,4.497-12.212,1.136-2.037,1.525-3.390,P＜0.05).(4) Correlation analysis between related prognostic indicators and tumor diameter:the results of univariate analysis showed that there was a correlation between lymph node metastasis,vascular invasion,histological differentiation and T staging of American Joint Committee on Cancer (AJCC) and tumor diameter of 2 cm as a cut-off point (x2 =6.063,4.950,8.770,9.069,P＜0.05).There was a correlation between surgical margin,lymph node metastasis,vascular invasion and histological differentiation and tumor diameter of 3 cm as a cut-off point (x2=10.251,9.919,5.485,15.632,P＜0.05).The results of multivariate analysis showed that lymph node metastasis and T staging of AJCC were independent related factors affecting tumor diameter of 2 cm as a cut-off point[odds ratio (OR) =1.882,2.104,95 ％CI:1.075-3.293,1.220-3.631,P＜0.05];surgical margin and lymph node metastasis were independent related factors affecting tumor diameter of 3 cm as a cut-off point (OR=3.187,2.211,95 ％CI:1.377-7.379,1.133-4.314,P＜0.05).Conclusions The 2 cm ＜ tumor diameter ≤ 3 cm,tumor diameter ＞ 3 cm,R1 resection,lymph node metastasis and low-differentiated tumor are the independent risk factors affecting the prognosis of patients with hilar cholangiocarcinoma.Three cm (T staging in De Oliveira staging system) as the second cut-off point is feasible,meanwhile,2 cm cut-off point may be become another potential tumor dividing point described in De Oliveira staging system.
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Objective To investigate the pathogenic mutations of BRCA1 and BRCA2 in patients with early-onset breast cancer(≤35 years) and explore the relationships between BRCA1/2 mutations and clinical features.Methods Seventy-four patients with early-onset breast cancer were enrolled,who were treated in Hospital 307 between September 2014 and June 2016.High-throughput sequencing was used to test the 49 exon sequences and adjacent sequences of BRCA1 and BRCA2.χ2 test was used to analyze the distribution of BRCA1/2 pathogenic mutations in each group that was set up according to clinical features.Results Fifteen mutations(20.27%) were identified,including 5(6.76%) in BRCA1 and 10(13.51%) in BRCA2.Eleven new pathogenic mutations were discovered,and BRCA1:c.5470_5477delTGCCCAAT was found in one patient.The frequency of BRCA1/2 mutations in the group with a family history of breast cancer or ovarian cancer was higher than in the group without a family history (40.91% vs 11.54%) (χ2=6.534,P=0.011).Conclusion BRCA1/2 pathogenic mutation is significant for early-onset breast cancer,especially for those with a family history of breast or ovarian cancer.The new mutations may be specific to Chinese people.BRCA1:c.5470_5477delTGCCCAAT may be the ancestor mutation among the Chinese.
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Objective To evaluate the efficacy and safety of antibacterial drugs conservative therapy versus appendectomy for treating simple acute appendicitis(AA).Methods Randomized controlled trials (RCT) on antibacterial drugs conservative therapy versus appendectomy for treating simple AA were retrieved from CBM (1978 June 2015),CNKI (1979-June 2015),Medline (1950-June 2015),Pubmed (1950-June 2015),Embase (1970-June 2015) and Cochrane library (issue 2,2015) by computer.The included RCTs were performed the data extraction according to the criteria of the Cochrane handbook by two researchers.Then the included d/literatures were performed the quality assessment and the extracted effective data were performed the meta analysis.Results Six RCTs were included involving 1510 patients with AA,among them,767 cases were treated with antibacterial drugs and 743 cases were treated with appendectomy.Compared with surgical treatment,the effect rate of antibacterial medication conservative therapy was decreased by 25.00％ (RD=-0.25,95％ CI:-0.35--0.14),the recurrence rate was increased by 48.43 times (OR=48.43,95％CI:16.94-138.44),the loss time of labor force was shortened by 1.52 d (MD=-1.52,95％ CI:-3.02 0.02),but the occurrence rate of complications(RD=-0.06,95％CI:-0.15 0.03),pain time(MD=-0.76,95％CI:-3.31 1.79),hospital stay time (MD=4.60,95％CI:-0.89 10.09) and sick leave time(MD=-2.39,95％CI:-5.62-0.84) had no statistical differences between the two kinds of treatment method(P＞0.05).Conclusion Appendectomy may be the gold standard method for treaung simple AA.
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Objective To construct humanized monoclonal antibodies against CD 20 and check their affinity to CD 20 antigen and their anti-tumor activity.Methods Based on the computer model , human IgG1 candidates closest to rituximab in crystal structure were selected in the Protein Data Bank ( PDB) .With the selected human IgG 1 candidates as the frame , we modified and transplanted the complementarity determining region ( CDR) of rituximab .First,the target gene fragments were obtained by overlapping PCR.Then, the sequences of the light chains(L) and the heavy chains(H) were inserted in-to the pcDNA3.3 and pOptiVEC vectors.Next, the constructed clones were transfected into 293F cells through transient transfection.After a large-scale cell culture, the mAb was purified by affinity chromatography rProtein A column.The puri-ty and expression level of the humanized antibodies was tested by sodium dodecyl sulfate ( SDS)-polyacrylamide gelelectro-phoresis(PAGE).The affinity of the humanized antibodies to CD20 was assessed with Fortebio assay.Finally, the anti-tumor activity of the constructed antibodies was detected by checking the tumor growth inhibition of the nude mice transplan-ted with tumor .Results Three humanized monoclonal antibodies against CD 20 were expressed and purified successfully . In reducing SDS-PAGE, the antibodies exhibited two bands of approximately 25 ×103 and 55 ×103 , respectively.The band size of the antibodies matched the expected value.Fortebio assay revealed that the humanized antibodies could bind to CD20 with high affinity (rituximab:6.48 ×10 -9mol/L, L4H7:1.91 ×10 -9mol/L, L5H5:7.35 ×10 -10mol/L,and L5H7:1.91 ×10 -9mol/L).The tumor growth inhibition experiment showed that the anti-tumor activity of L5H7 mAb was better than that of rituximab .Conclusion Three humanized monoclonal antibodies against CD 20 have been successfully construc-ted and expressed.L5H7 mAb possesses high affinity for CD20 and a good ability to kill tumor cells.