Therapeutic effect of Rab11 inhibitor cyclin-dependent kinase inhibitor-73 on liver fibrosis and its related mechanisms / 中华肝胆外科杂志

Objective:To investigate the therapeutic effect and potential molecular mechanisms of cyclin-dependent kinase inhibitor-73 (CDKI-73), the Rab11 inhibitor, on liver fibrosis.Methods:Human LX2 cells were divided into four groups: negative control group, transforming growth factor-β (TGF-β) group, CDKI-73 group and TGF-β+ CDKI-73 group. Fifteen 5-week-old female C57 mice with body weight of (18.04±0.62) g were divided into 3 groups with 5 mice in each group: control group (intraperitoneal injection of olive oil + vehicle gavage), carbon tetrachloride (CCl 4) group (intraperitoneal injection of CCl 4 + vehicle gavage) and CCl 4+ CDKI-73 group (intraperitoneal injection of CCl 4+ CDKI-73 gavage). Another 15 5-week-old female C57 mice with body weight of (18.06±0.34) g were divided into 3 groups with 5 mice in each group: sham operation group (Sham), bile duct ligation (BDL) group + vehicle group (BDL+ vehicle gavage) and bile duct ligation+ CDKI-73 group (BDL+ CDKI-73 gavage). The expression of α-smooth muscle actin (α-SMA) and fibronectin(FN)in LX2 cells were analyzed by Western blot. Masson and Sirius red were used to examine the liver fibrosis after CDKI-73 treatment in vivo. Immunohistochemistry (IHC) was utilized to examine the expression of α-SMA in mice liver. Results:Collagen content assessed by Sirius red and Masson staining and α-SMA expression evaluated by IHC were all increased in CCl 4 group compared with control group ( q=38.47, 24.99, 36.79). Moreover, the collagen content and α-SMA expression in CCl 4 + CDKI-73 treatment group were obviously decreased compared with CCl 4 group ( q=24.72, 14.87, 27.50), and the differences were statistically significant (all P<0.001). Compared with Sham group, collagen content and α-SMA expression in bile duct ligation group were increased ( q=28.23, 41.01, 44.16). Furthermore, in BDL group, after treatment with CDKI-73, the collagen content and α-SMA expression were notably decreased ( q=22.88, 34.31 and 33.97, all P<0.001). Consistent with in vivo results, the relative expression levels of α-SMA and FN protein in TGF-β group were higher than those in TGF-β+ CDKI-73 group (α-SMA: 3.71±0.34 vs. 1.28±0.31; FN: 3.21±0.39 vs. 0.83±0.06, all P<0.001). The mRNA relative expression levels of α-SMA and FN in TGF-β group were higher than those in TGF-β+ CDKI-73 group, and the differences were statistically significant ( P<0.001). However, the relative expression of TGF-β receptor Ⅱ protein in CDKI-73 group was higher than those in negative control group (4.68±0.63 vs. 1.00±0.22, P=0.004). The relative expression level of phosphorylated SMAD2 in TGF-β+ CDKI-73 group was lower than those in TGF-β group (1.67±0.24 vs. 3.99±0.44, P<0.001). Transwell assay showed that 0.5 μmol/L CDKI-73 could effectively inhibit the migration of LX2 cells, and the inhibitory ability became stronger with the increase of CDKI-73 concentration. Conclusion:CDKI-73 can inhibit the activation of hepatic stellate cells and liver fibrosis by inhibiting Rab11-dependent TGF-β signaling pathway both in vivo and in vitro.

Clinical diagnosis and treatment of liver perivascular epithelioid cell neoplasms / 中华肝胆外科杂志

Objective:To analyze the clinical features and prognosis of liver perivascular epithelioid cell neoplasms (PEComa).Methods:The clinical data of 12 patients with liver PEComa diagnosed by pathology at the First Affiliated Hospital of Xi 'an Jiaotong University from October 2011 to November 2021 were retrospectively analyzed. There were 1 male and 11 females, with a median age of 44 (range 20 to 63) years old. The clinical manifestations, laboratory examinations, imaging features, treatment methods, postoperative pathological features and treatment outcomes of these patients were collected and analysed. Postoperative follow-up by telephone or patient's follow-up records.Results:Among the 12 patients with hepatic PEComa, 8 patients (66.7%) were asymptomatic and 11 patients (91.7%) had a single lesion. All patients underwent surgical treatment, including local tumor resection in 10 patients (83.3%) and extended hemihepatectomy in 2 patients (16.7%). Enhanced CT showed the lesion to be a quasi-round homogeneous low-density mass, enhanced in arterial phase with hepatic artery branches in the lesion, and decrease in enhancement degrees in portal vein phase and delayed phase. Postoperative pathology of the lesions in all the 12 patients was benign. Immunohistochemical results showed that the positive rates of melanoma cell markers HMB45, Melan-A and smooth muscle actin were 100.0%(12/12), 83.3%(10/12) and 91.7%(11/12) respectively. The median follow-up period was 27 months, and no recurrence or metastasis was found.Conclusion:Hepatic PEComa occurred commonly in women with obscure symptoms. The lesion was mainly single and it had no correlation with hepatitis. It is easily confused with primary liver cancer and liver metastasis on medical imagings. PEComa expressed markers of both melanocyte and smooth muscle cell, and radical surgical resection resulted in good results.

Establishment and application value of a radiomics prediction model for lymph node metas-tasis of gallbladder carcinoma based on dual-phase enhanced CT / 中华消化外科杂志

Objective:To investigate the establishment and application value of a radio-mics prediction model for lymph node metastasis of gallbladder carcinoma based on dual-phase enhanced computed tomography (CT).Methods:The retrospective cohort study was conducted. The clinicopathological data of 194 patients with gallbladder carcinoma who were admitted to the First Affiliated Hospital of Xi'an Jiaotong University from January 2012 to December 2020 were collected. There were 70 males and 124 females, aged (64±10)years. All patients underwent curative-intent resection of gallbladder carcinoma. A total of 194 patients were randomly divided into 156 cases in training set and 38 cases in test set according to the ratio of 8:2 based on random number method in R software. The training set was used to establish a diagnostic model, and the test set was used to validate the diagnostic model. After the patients undergoing CT examination, image analysis was performed, radiomics features were extracted, and a radiomics model was established. Based on clinicopathological data, a nomogram prediction model was established. Observation indicators: (1) lymph node dissection and histopathological examination results; (2) establishment and characteristic analysis of a radiomics prediction model; (3) analysis of influencing factors for lymph node metastasis of gallbladder carcinoma; (4) establishment of a nomogram prediction model for lymph node metastasis; (5) comparison of the predictive ability between the radiomics prediction model and nomogram prediction model for lymph node metastasis. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were expressed as absolute numbers, and comparison between groups was performed by the chi-square test. Univariate analysis was conducted by the chi-square test, and multivariate analysis was performed by the Logistic regression model forward method. The receiver operating characteristic curve was drawn, and the area under curve, decision curve, confusion matrix were used to evaluate the predictive ability of prediction models. Results:(1) Lymph node dissection and histopathological examination results. Of the 194 patients, 182 cases underwent lymph node dissection, with the number of lymph node dissected as 8(range, 1?34) per person and the number of positive lymph node as 0(range, 0?11) per person. Postoperative histopathological examination results of 194 patients: 122 patients were in stage N0, with the number of lymph node dissected as 7(range, 0?27) per person, 48 patients were in stage N1, with the number of lymph node dissected as 8(range, 2?34) per person and the number of positive lymph node as 1(range, 1?3) per person, 24 patients were in stage N2, with the number of lymph node dissected as 11(range, 2?20) per person and the number of positive lymph node as 5(range, 4?11) per person. (2) Establishment and characteristic analysis of a radiomics prediction model. There were 107 radiomics features extracted from 194 patients, including 18 first-order features, 14 shape features and 75 texture features. According to the intra-group correlation coefficient and absolute median difference of each radiomics feature, mutual information, Select K-Best, least absolute shrinkage and selection operator regression were conducted to further reduce dimensionality. By further combining 5 different machine learning algorithms including random forest, gradient boosting secession tree, support vector machine (SVM), K-Nearest Neighbors and Logistic regression, the result showed that the Select K-Best_SVM model had the best predictive performance after analysis, with the area under receiver operating characteristic curve as 0.76 in the test set. (3) Analysis of influencing factors for lymph node metastasis of gallbladder carcinoma. Results of univariate analysis showed that systemic inflammation response index, carcinoembryonic antigen (CEA), CA19-9, CA125, radiological T staging and radiological lymph node status were related factors for lymph node metastasis of patients with gallbladder cancer ( χ2=4.20, 11.39, 5.68, 11.79, 10.83, 18.58, P<0.05). Results of multivariate analysis showed that carcinoembryonic antigen, CA125, radiological T staging (stage T3 versus stage T1?2, stage T4 versus stage T1?2), radiological lymph node status were independent influencing factors for lymph node metastasis of patients with gallbladder carcinoma [ hazard ratio=2.79, 4.41, 5.62, 5.84, 3.99, 95% confidence interval ( CI) as 1.20?6.47, 1.81?10.74, 1.50?21.01, 1.02?33.31, 1.87?8.55, P<0.05]. (4) Establishment of a nomogram prediction model for lymph node metastasis. A nomogram prediction model was established based on the 4 independent influencing factors for lymph node metastasis of gallbladder carcinoma, including CEA, CA125, radiological T staging and radiological lymph node status. The concordance index of the nomogram model was 0.77 (95% CI as 0.75?0.79) in the training set and 0.73 (95% CI as 0.68?0.72) in the test set, respectively. (5) Comparison of the predictive ability between the radiomics predic-tion model and nomogram prediction model for lymph node metastasis. The receiver operating characteristic curve showed that the areas under the curve of Select K-Best_SVM radiomics model were 0.75 (95% CI as 0.74?0.76) in the training set and 0.76 (95% CI as 0.75?0.78) in the test set, respectively. The areas under the curve of nomogram prediction model were 0.77 (95% CI as 0.76?0.78) in the training set and 0.70 (95% CI as 0.68?0.72) in the test set, respectively. The decision curve analysis showed that Select K-Best_SVM radiomics model and nomogram prediction model had a similar ability to predict lymph node metastasis. The confusion matrix showed that Select K-Best_SVM radiomics model had the sensitivity as 64.29% and 75.00%, the specificity as 73.00% and 59.09% in the training set and test set, respectively. The nomogram had the sensitivity as 51.79% and 50.00%, the specificity as 80.00% and 72.27% in the training set and test set, respectively. Conclusion:A dual-phase enhanced CT imaging radiomics prediction model for lymph node metastasis of gallbladder carcinoma is successfully established, and its predictive ability is good and consistent with that of nomogram.

Clinical efficacy of Atezolizumab and Bevacizumab in the treatment of initially borderline resectable advanced liver cancer / 中华消化外科杂志

Conversion therapy has become the core in the treatment of borderline resectable or unresectable liver cancer, which provides resectable opportunities for more advanced liver cancer patients. In accordance with the first-choice treatment regimen recommended by the guidelines, the authors reported a successful case of Atezolizumab and Bevacizumab (T+A regimen) conversion therapy. The patient with initially borderline resectable advanced liver cancer was performed liver segment resection sucessfully after conversion therapy, and non-tumor recurrence was observed at postoperative 9 months. Postoperative pathological examination showed combined hepatocellular-cholangiocarcinoma, which also indicated the important value of T+A regimen in the conversion therapy of combined hepatocellular-cholangiocarcinoma.

Research advances in SULF2 and its relationship with hepatocellular carcinoma / 中华肝胆外科杂志

Cell secreted sulfatase 2 is an endogenous sulphate esterase, which can hydrolyze the sulphate groups in extracellular matrix or on the chain of heparan sulphate on the outer surface of cell membrane, which can dissociate the growth factor bound to heparan sulphate proteoglycan, improve the local concentration of growth factor and activate the downstream signal. Sulfatase 2 is highly expressed in a variety of tumors, and the increased expression of sulfatase 2 in hepatocellular carcinoma is associated with poor prognosis. Sulfatase 2 can promote tumor progression by activating multiple signaling pathways in hepatocellular carcinoma cells. Inhibit the activity of hepatocellular carcinoma cell sulfatase 2, and then inhibit the proliferation, migration and tumorigenesis of hepatocellular carcinoma cells. In this paper, the research progress of sulfatase 2 and its role in the occurrence and development of hepatocellular carcinoma is summarized.

Pilot study of the relationship between clinical classification of gallbladder cancer and prognosis: a retrospective multicenter clinical study / 中华外科杂志

Objectives@#To propose a novel clinical classification system of gallbladder cancer, and to investigate the differences of clinicopathological characteristics and prognosis based on patients who underwent radical resection with different types of gallbladder cancer.@*Methods@#The clinical data of 1 059 patients with gallbladder cancer underwent radical resection in 12 institutions in China from January 2013 to December 2017 were retrospectively collected and analyzed.There were 389 males and 670 females, aged (62.0±10.5)years(range:22-88 years).According to the location of tumor and the mode of invasion,the tumors were divided into peritoneal type, hepatic type, hepatic hilum type and mixed type, the surgical procedures were divided into regional radical resection and extended radical resection.The correlation between different types and T stage, N stage, vascular invasion, neural invasion, median survival time and surgical procedures were analyzed.Rates were compared by χ2 test, survival analysis was carried by Kaplan-Meier and Log-rank test.@*Results@#Regional radical resection was performed in 940 cases,including 81 cases in T1 stage,859 cases in T2-T4 stage,119 cases underwent extended radical resection;R0 resection was achieved in 990 cases(93.5%).The overall median survival time was 28 months.There were 81 patients in Tis-T1 stage and 978 patients in T2-T4 stage.The classification of gallbladder cancer in patients with T2-T4 stage: 345 cases(35.3%)of peritoneal type, 331 cases(33.8%) of hepatic type, 122 cases(12.5%) of hepatic hilum type and 180 cases(18.4%) of mixed type.T stage(χ2=288.60,P<0.01),N stage(χ2=68.10, P<0.01), vascular invasion(χ2=128.70, P<0.01)and neural invasion(χ2=54.30, P<0.01)were significantly correlated with the classification.The median survival time of peritoneal type,hepatic type,hepatic hilum type and mixed type was 48 months,21 months,16 months and 11 months,respectively(χ2=80.60,P<0.01).There was no significant difference in median survival time between regional radical resection and extended radical resection in the peritoneal type,hepatic type,hepatic hilum type and mixed type(all P>0.05).@*Conclusion@#With application of new clinical classification, different types of gallbladder cancer are proved to be correlated with TNM stage, malignant biological behavior and prognosis, which will facilitate us in preoperative evaluation,surgical planning and prognosis evaluation.

Clinical effects and prognostic analysis of radical surgery for primary gallbladder cancer / 中华消化外科杂志

Objective To investigate the clinical effects and prognostic factors of radical surgery for primary gallbladder cancer (GBC).Methods The retrospective case-control study was conducted.The clinicopathological data of 305 patients with primary GBC who underwent radical Ro resection in the First Affiliated Hospital of Xi'an Jiaotong University from 2013 to 2017 were collected,including 108 males and 197 females,aged from 30 to 88 years,with a median age of 62 years.According to the different tumor staging,patients underwent corresponding operation and adjuvant treatment based on the postoperative indication of chemotherapy.Observation indicators:(1) results of imaging and laboratory examinations;(2) treatment situations:① surgical situations,② postoperative adjuvant treatment;(3) results of postoperative pathological examination;(4) followup;(5) prognostic factors analysis.Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival up to December 5,2018,and death was used as the end point.Measurement data with normal distribution were represented as Mean±SD.Measurement data with skewed distribution were described as M (range).Count data were represented as percentage.The survival curve and survival rate were respectively drawn and calculated using the Kaplan-Meier method.The univariate analysis and multivariate analysis were respectively done using the Log-rank test and COX regression model.Results (1) Results of imaging and laboratory examinations:results of imaging examination showed that diagnostic rates of ultrasound,CT and MRI examination were respectively 84.06％ (174/207),85.71％ (168/196) and 63.11％ (65/103).Results of laboratory examination showed that the positive rates of CA19-9,CA125 and carcinoembryonic antigen (CEA) were respectively 55.34％ (145/262),48.06％ (124/258) and 46.15％ (126/273).(2) Treatment situations:① surgical situations:305 patients underwent radical R0 resection for primary GBC,including 145 undergoing liver wedge resection + D2 lymph node dissection,61 undergoing liver wedge resection + D1 lymph node dissection,55 undergoing liver Ⅳ B and Ⅴ segmentectomy + D2 lymph node dissection,11 undergoing liver Ⅳ B and Ⅴ segrnentectomy + D1 lymph node dissection,9 undergoing right hepatectomy + D2 lymph node dissection,5 undergoing liver wedge resection + D2 lymph node dissection + partial colectomy,4 undergoing pancreaticoduodenectomy,3 undergoing simple cholecystectomy in Tis stage,3 undergoing right hepatectomy + D1 lymph node dissection,2 undergoing liver ⅣB and Ⅴ segmentectomy + D2 lymph node dissection + partial colectomy,1 undergoing liver Ⅳ B and Ⅴ segmentectomy + resection and reconstruction of portal vein + D2 lymph node dissection,1 undergoing liver ⅣB and Ⅴ segmentectomy + D2 lymph node dissection + partial resection of the stomach or duodenum,1 undergoing pancreaticoduodenectomy + resection and reconstruction of portal vein,1 undergoing right hepatectomy + pancreaticoduodenectomy,1 undergoing right hepatic lobectomy + partial gastrectomy + D2 lymph node dissection,1 undergoing right hepatic lobectomy + D1 lymph node dissection and 1 undergoing right hepatic trilobectomy + D2 lymph node dissection.Of 94 patients with unsuspected GBC,78 who were diagnosed in the other hospitals received salvage surgery in the authors' center.Twenty-one patients had postoperative surgery-related complications,including 11 with bile leakage,8 with pulmonary infection and 2 with abdominal bleeding.Two patients died in the perioperative period.② Postoperative adjuvant treatment:26 patients underwent postoperative adjuvant chemotherapy.Chemotherapy regimen:gemcitabine + oxaliplatin were used in 12 patients,gemcitabine + tegafur in 7 patients,gemcitabine + cisplatin in 6 patients,oxaliplatin + tegafur in 1 patient.(3) Results of postoperative pathological examination.The postoperative pathological type of 305 patients:257,23,6,5,4,3,3,2,1 and 1 patients were respectively confirmed as pure adenocarcinoma,adenocarcinoma combined with squamous cell carcinoma,adenocarcinoma combined with neuroendocrine carcinoma,mucinous adenocarcinoma,neuroendocrine carcinoma,adenocarcinoma combined with mucinous carcinoma,squamous cell carcinoma,sarcomatoid carcinoma,adenocarcinoma combined with sarcomatoid carcinoma,adenocarcinoma combined with signet-ring cell carcinoma.Degree of tumor differentiation:highdifferentiated,moderate-differentiated and low-differentiated tumors were detected in 37,130 and 121 patients,respectively,17 with unknown differentiated degree.Of 305 patients,16 and 32 patients had respectively vascular invasion and nerve invasion.The number of lymph node dissected of 305 patients was 8±5,with positive lymph node of 0 (range,0-9),including 121 with lymphatic metastasis (26 with jumping lymphatic metastasis).TNM staging of 305 patients:stage 0,Ⅰ,Ⅱ,ⅢA,ⅢB,ⅣA and ⅣB were detected in 7,18,13,137,57,11 and 62 patients,respectively.(4) Follow-up:245 of 305 patients were followed up for 18.0 months (range,6.0-70.0 months).The survival time,1-and 3-year survival rates were respectively 29.5 months (range,0.5-69.9 months),71.6％ and 45.8％.One hundred and twenty-two patients died during the follow-up.(5) Prognostic factors analysis:the results of univariate analysis showed that preoperative level of bilirubin,pathological type,degree of tumor differentiation,liver invasion,vascular invasion,nerve invasion,T staging,N staging and postoperative chemotherapy were factors affecting prognosis of patients with primary GBC (x2 =10.26,3.96,45.89,34.64,12.75,27.05,35.09,39.44,4.40,P＜0.05).The results of multivariate analysis showed that low-differentiated tumor,liver invasion and N2 staging were independent risk factors affecting prognosis of patients with primary GBC [odds ratio (OR)=1.90,1.71,1.46,95％ confidence interval (CI):1.34-2.70,1.15-2.52,1.17-1.82,P＜0.05],and postoperative chemotherapy was a protective factor affecting prognosis of patients with primary GBC (OR=0.35,95％ CI:0.15-0.82,P＜0.05).Conclusions For patients with primary GBC undergoing radical resection,D2 lymph node dissection should be performed routinely.The low-differentiated tumor,liver invasion and N2 staging are independent risk factors affecting prognosis of patients,and postoperative chemotherapy is a protective factor.

Treatment strategies of reoperation of benign biliary tract diseases in the era of precision surgery / 中华消化外科杂志

Reoperation on biliary tract diseases is a kind of complex and difficult surgery,with the high risk and recurrence rate.Benign biliary tract diseases included residual and recurrence of bile duct stone,bile duct injury and benign biliary stricture,which are still the most common causes for reoperation.The common causes,application of the precision surgery and new mode of multidisciplinary team (MDT) for the reoperation on benign biliary diseases were explored in this paper.With the techniques developments of minimal invasive and precision surgery,the new mode of MDT for the reoperation on benign biliary diseases will provide the best individual diagnosis and treatment to the patients.

Activated hepatic stellate cells and its relationship with hepatocellular carcinoma / 中华肝胆外科杂志

Interactions between hepatocellular carcinoma (HCC) cells and the tumor stromal microenvironment have profound effects on tumor growth,epithelial-mesenchymal transition (EMT),invasion and metastasis.Activated hepatic stellate cells (HSCs) are the major subtype of stromal cells in the liver tumor microenvironment.HCC cells can induce the activation of HSCs during carcinogenesis,while activated HSCs promote HCC cells growth and migration through secreting growth factors,inducing angiogenesis and immune suppression.Bidirectional interactions between HCC cells and HSCs may function as an ＂amplification loop＂ to further enhance metastatic growth in the liver.In this review,we summarized the most recent data from the research on HSCs and its relationship with HCC.

Inhibition of lipid peroxidation and protective effects on diabetic mice of extracts from Coreopsis tinctoria Nutt. in Xinjiang / 中国药理学通报

Aim To compare the inhibition of lipid peroxidation of ethyl acetate extract( EAE) and n-buta-nol( BE) extract from Coreopsis tinctoria Nutt. in vitro. To investigate the parameters such as body weight, bio-chemical indexes in plasma, and viscera indexes on type 2 diabetes mice by intraperitoneal injection of streptozotocin ( STZ ) . Methods The extracts were prepared by response surface methodology. The ex-tracts were suspended in distilled water and defatted with petroleum ether. The aqueous layer was succes-sively extracted with ethyl acetate and n-butanol. The inhibition of lipid peroxidation activity was determined by thiobarbituric acid method. The effects of extract BE on diabetic mice were observed at the dosage of 0. 2,0. 4,0. 8 g·kg-1 ( ig) for 4 weeks. The parame-ters were observed such as weight of body changes, or-gan coefficients of liver, pancreas and kidney, bio-chemical indexes in plasma and viscera pathological sections. Results In the linoleic acid reaction system, the SC50 value of the EAE and BE was ( 443. 96 ± 11. 24) mg·L-1, (840. 29 ± 16. 38) mg·L-1, re-spectively, and that in rat liver homogenate was (23. 59 ± 3. 67 ) mg · L-1 , ( 60. 37 ± 4. 27 ) mg · L-1 , respectively. Compared with diabetic model group, BE could significantly improve the trend of weight loss, and increase viscera indexes. The patho-logical sections showed that BE had the recovery and improvement effects on the damage of liver, pancreas and kidney. Conclusions The extracts of C. tinctoria have a certain anti-lipid peroxidation activity in vitro. And BE has a certain capacity to improve and repair damaged organs for DM mice.

Application of Myofascial Trigger Points Theory in Clinical Practice of Sports Rehabilitation (review) / 中国康复理论与实践

This article demonstrated the myofascial trigger points theory and the application of related techniques in the clinical prac-tice of sports rehabilitation, such as the treatment of athletes injury pain, rehabilitation of movement function limitation, elimination of sports fatigue and so on. The clinical treatments based on the myofascial trigger points theory are simple, effective, noninvasive, and with short recovery time and low recurrence rate. It provides scientific theoretical and practical foundation for the prevention, diagnosis, treat-ment and rehabilitation for sport injury.

Application of endoscopic retrograde cholangiopancreatography drainage in surgical treatment of hilar cholangiocarcinomas / 中国综合临床

Objective To explore the feasibility,efficacy and safety of endoscopic retrograde cholangio?pancreatography ( ERCP ) drainage during peroperation of hilar cholangiocarcinoma for alleviate jaun?dice. Methods Nineteen cases patients with hilar cholangiocarcinoma who were treated with ERCP in the First Affiliated Hospital of Xi'an Jiao Tong University from January 2013 to December 2013,the drainage way,efficient rate,complication rate,and surgical situation were retrospective analyzed. Results Bilateral endoscopic drain?age was one?time achieved in all 19 patients. Among them,Eendoscopic nasobiliary drainage( ENBD) for unilat?eral bilateral drainage was 4 cases,ENBD and plastic stent for unilateral( left or right) drainage was 9 cases,EN?BD and plastic stent for bilateral drainage was 6 cases. The drainage efficiency rate was 89. 5% ( 17/19) . Serum alanine aminotransferase(ALT),total bilirubin(TBIL),direct bilirubin(DBIL),alkaline phosphatase(ALP) and Prothrombin time (PT) were significantly decreased after 7days post?ERCP((208. 4±47. 7) U/L vs. (90. 3 ±31. 57) U/L,(421. 7±85. 9) μmol/L vs. (150. 1±49. 7) μmol/L,(294. 6±30. 6) μmol/L vs. (95. 4±23. 2)μmol/L,(853. 1±133. 7) U/L vs. (600. 0±116. 4) U/L,(17. 7±1. 8) s vs. (13. 8±1. 0) s;P=0. 000,0. 001, 0. 000,0. 001,0. 004) . There were 6 cases occurred ERCP postoperative complications,including 2 cases of hy?peramylasemia, 1 case of pancreatitis, 3 cases of cholangitis. Seven cases of hilar cholangiocarcinoma patients were received hilar radical surgery by combination caudate lobectomy of the left or right hepatectomy,no postop?erative cholangitis was occurred. Conclusion ERCP biliary drainage is an important means to ensure the perio?perative safety and efficacy of hilar cholangiocarcinoma.

Construction and appraisal of recombinant adeno-associated virus vector for expressing shRNA targeting CIP2A mRNA / 西安交通大学学报(医学版)

Objective To construct the recombinant adeno-associated virus vector carrying cancerous inhibitor of PP2A (CIP2A)short hairpin RNA (shRNA)for preparation of high-titer viruses.Methods The small hairpin RNA of CIP2A (CIP2A shRNA)was designed,synthesized and cloned into pDC31 6-EGFP-U6 plasmid which was double digested by Bam HⅠ and Hin dⅢ.The resultant plasmid pDC31 6-EGFP-shRNA was confirmed and served as template to appraise primers.EGFP-CIP2A shRNA sequence was amplified by PCR,double digested with Eco RⅠand Sal Ⅰ and ligated to pSNAV2.0 plasmid digested with the same enzyme pair.pSNAV2.0-EGFP-CIP2A shRNA plasmid DNA was prepared,purified,identified and transfected into BHK-21 cells.BHK-21 cells expressing CIP2A shRNA (BHK-21/CIP2A-shRNA ) were obtained and subsequently infected with VGTC’s proprietary AAV packaging system to package the rAAV2-CIP2A shRNA.After purification,the functional and infectious virus was obtained and the titer of virus was detected.Real-time PCR and Western blot methods were used to detect the expression of CIP2A after infection with HepG2 cells,and the empty viral vector rAAV2-EGFP was used as control. Results A recombinant adeno-associated virus-2 vector carrying CIP2A shRNA was constructed successfully.The presence of the target sequence in the vector was confirmed by double enzyme digestion and sequencing.By transfecting the pSNAV2.0-EGFP-CIP2A shRNA plasmid into BHK-21 cells,BHK-21/CIP2A shRNA cells were infected with helper virus HSV1-rc/ΔUL2 to package the rAAV2-CIP2A shRNA to obtain a functional and infectious virus.The titer of the recombinant virus was 0.25×10 1 2 v.g./mL.The expression of CIP2A mRNA and screening value of 1×10 5 MOI effected HepG2 cells.Conclusion A high-titer recombinant adeno-associated virus-2 vector carrying CIP2A shRNA has been constructed successfully.

The value of MRCP combined with CT or MRI dynamic contrast-enhanced scan in biliary obstruction / 实用放射学杂志

Objective To investigate the value of MRCP in conjunction with CT or MRI contrast-enhanced scan in locating and qualitative diagnosis of biliary obstruction.Methods 954 patients with biliary obstruction confirmed by surgical pathology and clini-cal follow up underwent MRCP scans in our hospital.Contrast-enhanced CT scans in 87 patients,contrast-enhanced MRI scans in 52 and both CT and MRI enhancement in 37 were performed.Results The accuracy of location of biliary obstruction with MRCP was 100%,the accuracy of quality of biliary obstruction with MRCP combined with CT or MRI dynamic contrast-enhanced scan was 96%.Conclusion MRCP combined with CT or MRI dynamic contrast-enhanced scans has an important clinical value for the locali-zation and qualitative diagnosis of biliary obstruction.

Segment-orientated anatomical liver resection for the treatment of hepatic alveolar echinococcosis in the middle lobe of the liver / 中华消化外科杂志

Objective To investigate the efficacy and feasibility of segment-orientated anatomical liver resection for the treatment of hepatic alveolar echinococcosis (HAE) in the middle lobe of the liver.Methods The clinical data of a female patient with HAE in the middle lobe of the liver who was admitted to the First Affiliated Hospital of Xi'an Jiaotong University in September 2013 were retrospectively analyzed.Before operation,various surgical plannings were facilitated by a three-dimensional reconstruction system,and then the surgical planning was determined with the assistance of the multivariate analysis (volume measurement of liver,resectability of remnant functional liver,evaluation of vascular resection and reconstruction,Child-Pugh score and indocyanine green retention at 15 minutes).Segment-orientated anatomical liver resection(segment Ⅴ,Ⅷ and Ⅳb) was performed on the patient.There was a close relationship between the HAE and the first and the second hepatic portal during operation,and the anatomical liver resection of segment Ⅴ,Ⅷ and Ⅳb was precisely carried out.The patient was followed up by outpatient examination and telephone interview every month up to April 2014.The condition of the liver was observed by B ultrasound and computed tomography examinations.Results The three-dimensional reconstruction of the CT data of the patient clearly displayed the anatomical structure and adjacent relationship between the tumor,abdominal organs and major abdominal vessels.The preoperative evaluation of the anatomy of tumor based on three-dimensional images was confirmed with operative findings.The operation time and volume of blood loss were 410 minutes and 1 000 mL,respectively.The patient did not receive blood transfusion.The intraoperative vital signs of the patient were stable.There were no complications such as hepatic insufficiency.The duration of postoperative hospital stay was 15 days.Surgical incision was healed at discharge.The results of blood routine and blood biochemistry test,daily diet and basic self-care ability were in normal condition.HAE was diagnosed based on the result of pathological examination.Albendazole was administered with 1 200 mg/d after operation.The patient was followed up for 6 months and returned to work.The weight of the patient increased by 5 kilograms than that at discharge,without complaint of discomfort.There was no recurrence of HAE and hepatic echinococcosis of organs.Conclusions Segment-orientated anatomical liver resection is not only a method for complete resection,but also maximizes the functional remnant of liver on the basis of intraoperative three-dimensional reconstruction system together with selective hepatic inflow occlusion and vessel reconstruction technique.The patient gets a full recovery with satisfactory outcome.

Expression of mucin 15 in hepatocellular carcinoma and its clinical implications / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expression of mucin 15 (MUC15) in hepatocellular carcinoma and explore its association with the prognosis of patients.</p><p><b>METHODS</b>The expression of MUC15 was detected by quantitative RT-PCR and Western blotting in liver cell line L02, liver cancer cell lines HepG2, MHCC-97H, and SMMC-7721, and in 122 HCC and corresponding adjacent non-tumor liver tissues. The association of MUC15 expression in HCC tissues with the clinical parameters and the patients' survival was analyzed.</p><p><b>RESULTS</b>The 1iver cell line L02 showed significantly higher MUC15 expression level than the liver cancer cell lines HepG2, MHCC-97H, and SMMC-7721 (P<0.05). The expression level of MUC15 was markedly lower in the HCC tissues than in the adjacent non-tumor liver tissues (P<0.05). MUC15 expression in the HCC tissues was significantly correlated with the tumor TNM stage, intrahepatic or lymphatic metastasis, portal vein thrombosis and tumor differentiation (P<0.05). Kaplan-Meier survival analysis suggested that a low MUC15 expression was associated with a poor clinical prognosis of the patients.</p><p><b>CONCLUSION</b>The expression of MUC15 is correlated with the clinicopathological features and prognosis of HCC patients, and may potentially serve as a novel prognostic marker for HCC.</p>

MicroRNA-218 expression and its role in hepatocellular carcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expression of microRNA-218 (miR-218) and its role in hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>Forty-six pairs of fresh surgical specimens of HCC and adjacent tissues were examined for miR-218 expression using qRT-PCR. A miR-218 mimic was transfected into HepG2 cells, and the cell viability and apoptosis were analyzed by MTT assay and flow cytometry, and the potential targets of miR-218 were detected by qRT-PCR and Western blotting.</p><p><b>RESULTS</b>The expressions of miR-218 in HCC tissues were significantly down-regulated compared to those in the adjacent tissues (P<0.05). Down-regulation of miR-218 was found to correlate significantly with the tumor size (>5 cm) and an advanced TNM stage (III+IV) (P<0.05). Ectopic expression of miR-218 in HepG2 cells resulted in suppressed cell proliferation and enhanced cell apoptosis as well as the down-regulation of Bmi-1 and CDK6 mRNA and protein expressions (P<0.05).</p><p><b>CONCLUSION</b>The low-expression of miR-218 is correlated with malignant clinicopathological characteristics of HCC, and miR-218 may inhibit cell proliferation and promote cell apoptosis by down-regulating Bmi-1 and CDK6 in HCC.</p>

Concomitant precise hemihepatectomy for the treatment of hilar cholangiocarcinoma / 中华消化外科杂志

Objective To investigate the efficacy of concomitant precise hemihepateetomy for the treatment of hilar cholangiocarcinoma.Methods The clinical data of 38 patients with hilar cholangiocarcinoma who received concomitant precise hemihepatectomy at the First Affiliated Hospital of Xi'an Jiaotong University from January 2009 to October 2012 were retrospectively analyzed.All patients were examined by B ultrasonography,computed tomography (CT),magnetic resonance cholangiopancreatography (MRCP) and CT angiography (CTA)preoperatively.The hepatic function was tested before operation.Of the 7 patients with obstructive jaundice,5 received percutaneous transhepatic cholangial drainage,and 2 received endoscopic nosalbiliary drainage.Surgical procedures were determined according to the results of imaging examination.The resection of hilar cholangiocarcinoma,postoperative histopathological examination,pre-and postoperative hepatic function and prognostic indicators were analyzed.The count data and measurement data were analyzed using the chi-square test and t test,respectively; the survival curve was drawn by Kaplan-Meier method,and the survival rate was analyzed using the Log-rank test.COX proportion hazards model was used for multivariate analysis.Results The positive rates of B ultrasonography,CT and MRCP were 65.8％ (25/38),71.1％ (27/38) and 89.5％ (34/38),respectively.The results of 5 patients who received CTA were positive.Concomitant left hemihepatectomy was performed on 28 patients,concomitant right hemihepatectomy on 10 patients; concomitant caudate lobectomy on 22 patients,concomitant resection and reconstruction of portal vein on 4 patients (including 1 patient who received left hepatic vein repair),concomitant hepatic artery resection on 12 patients (including 3 patients who received hepatic artery reconstruction).Of the 38 patients,R0 resection was performed on 32 patients,R1 resection on 4 patients,R2 resection on 2 patients.Hepatic function indicators including total bilirubin,direct bilirubin,alkaline phosphatase,gamma-glutamyl-transferase,alanine aminotransferase and aspartate aminotransferase were significantly decreased after operation (t =7.799,8.445,5.697,6.633,4.469,4.140,P ＜ 0.05).Two patients died perioperatively,with the mortality rate of 5.3％ (2/38).The main postoperative complications included bile leakage and hepatic function insufficiency,with the incidences of 28.9％ (11/38) and 21.1％ (8/38),respectively.Postoperative histopathological findings included 31 patients with invasive adenocarcinoma,5 patients with nodular adenocarcinoma,1 patient with mucinous adenocarcinoma and 1 patient with adenosquamous carcinoma.The overall 1-,2-,3-year survival rates were 66％,37％ and 21％,and the median survival time was 22.0 months.There were significant differences in the survival rates between patients who received R0 resection and those with R1/R2 resection,and between patients with N0 and N1/N2 stage (x2 =4.516,10.397,P ＜ 0.05).The results of multivariate analysis showed that positive margin and lymph node metastasis were prognostic indicators.Conclusions Concomitant precise hemihepatectomy has significantly improved the radical resection rate and the efficacy of treatment for hilar cholangiocarcinoma.Comprehensive preoperative imaging examination and hepatic function test are important for the assessment for resectability of hilar cholangiocarcinoma.Selective preoperative biliary drainage are key points to decrease postoperative morbidity and morality.

Double lethal effects of fusion gene of wild-type p53 and JunB on hepatocellular carcinoma cells / 华中科技大学学报（医学）（英德文版）

This study explored the double lethal effects of pEGFP-C1-wtp53/junB fusion gene on hepatocellular carcinoma (HCC) cells. wtp53/junB fusion gene was constructed and transformed into HepG2 cell line. Expression of KAI1 was detected by quantitative real-time PCR and Western blotting, cells apoptosis rate was detected by flow cytometry, proliferation of cells was detected byMTT chromometry, cell transmigration was detected by using transwell systems. The results showed that after transformation with pEGFP-C1-wtp53/JunB, the expression level of KAI1 protein was up-regulated, being 8.13 times the blank control group in HepG2 cells and significantly higher than 2.87 times which transformed with pEGFP-C1-JunB, 3.11 times which transformed with pEGFP-C1-wtp53 (P<0.001). Apoptosis rate of HepG2 cells transformed with pEGFP-C1-wtp53/JunB was significantly higher than that of other groups (P<0.001), and invasive ability of HepG2 cells transformed with pEGFP-C1-wtp53/JunB was significantly lower than other groups(P<0.001). It was concluded that the fusion gene of wtp53 and JunB could not only inhibit the growth of hepatoma cells and promote tumor cell apoptosis, but also suppress the invasive ability of tumor cells by up-regulating the expression of KAI1.

Double lethal effects of fusion gene of wild-type p53 and JunB on hepatocellular carcinoma cells / 华中科技大学学报（医学）（英德文版）

This study explored the double lethal effects of pEGFP-C1-wtp53/junB fusion gene on hepatocellular carcinoma (HCC) cells. wtp53/junB fusion gene was constructed and transformed into HepG2 cell line. Expression of KAI1 was detected by quantitative real-time PCR and Western blotting, cells apoptosis rate was detected by flow cytometry, proliferation of cells was detected byMTT chromometry, cell transmigration was detected by using transwell systems. The results showed that after transformation with pEGFP-C1-wtp53/JunB, the expression level of KAI1 protein was up-regulated, being 8.13 times the blank control group in HepG2 cells and significantly higher than 2.87 times which transformed with pEGFP-C1-JunB, 3.11 times which transformed with pEGFP-C1-wtp53 (P<0.001). Apoptosis rate of HepG2 cells transformed with pEGFP-C1-wtp53/JunB was significantly higher than that of other groups (P<0.001), and invasive ability of HepG2 cells transformed with pEGFP-C1-wtp53/JunB was significantly lower than other groups(P<0.001). It was concluded that the fusion gene of wtp53 and JunB could not only inhibit the growth of hepatoma cells and promote tumor cell apoptosis, but also suppress the invasive ability of tumor cells by up-regulating the expression of KAI1.