[The comparison between endoscopic and surgical treatment of delayed iatrogenic bile duct injury by propensity score matching].

Objective: To compare the safety and clinical efficacy of endoscopic and surgical treatment of patients with delayed iatrogenic bile duct injury (DBDI) with severity (SG) grade 1 to 2. Methods: The clinical data of 129 patients with SG grade 1 to 2 DBDI who received endoscopic or surgical treatment in the First Hospital of Lanzhou University from November 2007 to November 2021 were retrospectively collected. There were 46 males and 83 females,aged (M(IQR)) 54(22)years(range: 21 to 82 years). The baseline data of the two groups were matched 1∶1 by propensity score matching(caliper value was 0.2). Independent sample t test,rank sum test,χ2 test or Fisher exact probability test were used to analyze the data of the two matched groups. Results: There were 48 patients in each of the endoscopic treatment and surgical groups after matching,and there was no difference in general information between the two groups(both P>0.05). The bile duct injury-repair interval and intraoperative anesthesia complications were not statistically significant between the two groups after matching(all P>0.05). Compared with the surgical group, patients in the endoscopic treatment group had significantly shorter operative time(50 (30) minutes vs. 185 (100) minutes, Z=7.675,P<0.01) and postoperative hospital stay(5 (5) days vs. 12 (7) days, Z=5.848, P<0.01).For safety,there was no statistical difference in the incidence of immediate postoperative complications between the two groups with Clavien-Dindo classification of surgical complications<Ⅲ;the incidence of serious postoperative complications (Clavien-Dindo classification of surgical complications≥Ⅲ) was significantly higher in the surgical group than in the endoscopic treatment group(P=0.012). The incidence of long-term postoperative complications was not statistically different between the two groups(28.1% vs. 20.7%,P=0.562). In terms of efficacy,the postoperative liver function indexes of patients in both groups improved significantly compared with the preoperative period and returned to normal or near normal levels; the postoperative infection indexes of both groups showed an increasing trend,but were within the normal range. Of the 96 patients in both groups,61 obtained follow-up,and the follow-up time was (89.4±48.0)months(range: 3 to 165 months),and there was no statistical difference between the two groups(P=0.079). The probability of excellent long-term follow-up (78.1% vs. 86.2%) was not statistically different between the two groups(P=0.412).In patients with Strasberg-Bismuth type E1,the probability of excellent long-term follow-up was higher in the endoscopic treatment group compared with the surgical group(13/14 vs. 2/5,P=0.037). Conclusions: For DBDI patients with SG grade 1 to 2 and bile duct continuity,endoscopy can be used as the first deterministic treatment. The advantages of endoscopic therapy compared to surgery are the lower incidence of postoperative serious complications,and the shorter duration of surgery and postoperative hospital stay.

[Development of a Ranking Tool for Scientificity, Transparency and Applicability of Clinical Practice Guidelines].

Objective: To address the limitations of existing methods and tools for evaluating clinical practice guidelines, we aimed to develop a comprehensive instrument focusing on the three main dimensions of guideline development: scientificity, transparency, applicability. We will use it to rank the guidelines according to the scores. We abbreviated it as STAR, and its reliability, validity and usability were also tested. Methods: A multidisciplinary expert working group was set up, including methodologists, statisticians, journal editors, medical professionals, and others. Scoping review, Delphi methods and hierarchical analysis were used to determine the final checklist of STAR. Results: The new instrument contained 11 domains and 39 items. Intrinsic reliability of each domain was indicated by Cronbach's α coefficient, with a average value of 0.646. The Cohen's kappa coefficients for methodological evaluators and clinical evaluators were 0.783 and 0.618. The overall content validity index was 0.905. The R2 for the criterion validity analysis was 0.76. The average score for usability of the items was 4.6, and the mean time spent to evaluate each guideline was 20 minutes. Conclusion: The instrument has good reliability, validity and evaluating efficiency, and can be used for evaluating and ranking guidelines more comprehensively.

[Clinical observation of surgical resection combined radiofrequency in patients with CNLC â ¡a~â ¢a stage multiple hepatocellular carcinoma].

Objective: To investigate the effects of four therapeutic methods in the comprehensive treatment of China liver cancer staging (CNLC)Ⅱa~Ⅲa stage multiple hepatocellular carcinoma. Method: A retrospective study was conducted to collect clinical data of patients with multiple hepatocellular carcinoma (CNLC stage Ⅱa-Ⅲa), who received transhepatic arterial chemoembolization (TACE group, 73 cases), radiofrequency ablation (RFA group, 70 cases), TACE combined RFA (TACE combined RFA group, 69 cases) and surgical resection combined RFA (surgical resection combined RFA group, 57 cases) in the First Hospital of Lanzhou University from January 11, 2010 to January 31, 2017. The general data of age, gender, primary tumor, and laboratory examination were collected. The differences in overall survival rates and the survival rates among stratified subgrouping with different clinical factors between the four groups of patients were compared by the Kaplan-Meier method. Cox proportional hazards regression model analyzed the prognostic factors. Result: A total of 269 patients were enrolled and there were 194 males and 59 females with a median age of 58 years ranging from 23 to 84. The TACE group's 1, 3, and 5-year survival rates were 43.5%, 10.2%, and 0, respectively. The RFA group were 46.3%, 17.7%, and 0, respectively. The TACE combined RFA group were 56.8%, 21.5%, and 2.3%, respectively. The surgical resection combined RFA group was 76.5%, 38.7%, and 3.8%, respectively. The surgical resection combined RFA group has the best outcome(P<0.05). Univariate analysis showed that surgery combined RFA, tumor diameter<5 cm, no vascular invasion, preoperative AFP≤400 µg/L and TB<34 µmol/L are protective factors to improve the survival prognosis of patients with CNLCⅡa~Ⅲa stage multiple hepatocellular carcinoma(HR=0.784,0.718,0.633,0.846,0.617;all P<0.05). Multivariate Cox analysis showed that surgery combined RFA, tumor diameter<5 cm, preoperative AFP≤400 µg/L were independent risk prognostic factors for CNLCⅡa-Ⅲa stage multiple hepatocellular carcinoma (HR=0.702,0.743,0.647;all P<0.05). Conclusions: Surgical resection combined RFA is an effective method for the treatment of stage Ⅱa-Ⅲa hepatocellular carcinoma. Surgical resection combined RFA has more advantages in treatment patients with complicated hepatocellular carcinoma whose diameter<5 cm, tumor number<3, and preoperative AFP≤400 µg/L. Surgical resection combined RFA, tumor diameter<5 cm, preoperative AFP≤400 µg/L are independent influencing factors for the survival prognosis of patients with complicated hepatocellular carcinoma.

Effect of Bcl-2-siRNA on proliferation and apoptosis of pediatric acute B lymphoblastic leukemia (A-BLL) cells.

This study analyzed the effect of small interfering RNA specific for the Bcl-2 gene (siRNA Bcl-2) on the proliferation and chemotherapeutic sensitivity of pediatric A-BLL cells. Marrow samples were obtained from sixty newly-diagnosed A-BLL pediatric patients. The Bcl-2 mRNA expression in these samples was quantified by real time polymerase chain reaction. The Bcl-2 mRNA re-expression was analyzed by RNA interference using Bcl-2-siRNA. Cellular proliferation was detected using the MTT (Thiazolyl Blue Tetrazolium Bromide) assay. The cell apoptosis was quantified by flow cytometry. The Bcl-2 mRNA expression was significantly higher in the drug-resistance group than in the chemotherapy sensitivity group prior to chemotherapy (P < 0.05). In addition, the Bcl-2 mRNA expression in the chemotherapy sensitivity group was significantly higher before chemotherapy than that after chemotherapy (P < 0.05). The Bcl-2 mRNA expression significantly decreased in the leukemic cells of the Bcl-2-siRNA transfection group. We observed statistically significant differences in the relative mRNA expression levels among the Bcl-2-siRNA transfection, blank control, liposome empty transfection, and unrelated sequence oligonucleotide groups (P < 0.05). The rate of apoptosis in pediatric A-BLL leukemic cells was observed to increase significantly after transfection with Bcl-2-siRNA compared to the control, liposome empty transfection, and unrelated sequence oligonucleotide groups (P < 0.05). Therefore, we concluded that Bcl-2-siRNA can successfully inhibit the multiplicative capacity of A-BLL leukemic cells and promote apoptosis.

5-Azacytidine suppresses the proliferation of pancreatic cancer cells by inhibiting the Wnt/ß-catenin signaling pathway.

5-Azacytidine has been shown to be an effective anti-pancreatic cancer drug, but the mechanism remains unknown. In the current study, we explored the effect of 5-azacytidine on abnormal activation of the Wnt-ß-catenin signaling pathway in pancreatic cancer cells. The human pancreatic cancer cell line Bxpc-3 was treated with different concentrations of 5-azacytidine for various times. The proliferation and early apoptosis of the cells were evaluated using the CCK8 method and flow cytometry, respectively. mRNA and protein expression of ß-catenin, c-myc, and cyclinD1 were detected using real-time fluorescent quantitative polymerase chain reaction and Western blot analysis, respectively. The proliferation of Bxpc-3 cells was suppressed by 5-azacytidine. The early apoptosis of the cells was significantly enhanced over time and with increasing drug concentrations. The expression of ß-catenin, c-myc, and cyclinD1 were down-regulated, showing significant differences between different concentrations and treatment times (P < 0.05). 5-Azacytidine suppressed the proliferation of pancreatic cancer cells by inhibiting the Wnt/ß-catenin signaling pathway, particularly the expression of ß-catenin, c-myc, and cyclinD1. This study may provide a new potential strategy for diagnosing and treating pancreatic cancer.