The predictive model of microvascular invasion in hepatocellular carcinoma established based on multimodality imaging / 中华超声影像学杂志

Objective:To explore the risk factors of microvascular invasion (MVI) in hepatocellular carcinoma (HCC), and to predict MVI preoperatively, non-invasively and accurately.Methods:A total of 150 HCC patients (183 HCC lesions) were retrospectively collected in the First Affiliated Hospital of Xi′an Jiaotong University from January 2016 to June 2022.The clinical data and hematological data, gray-scale ultrasonography (US), contrast-enhanced ultrasonography (CEUS), enhanced magnetic resonance imaging with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (EOB-MRI) and pathological data of these patients were recorded. According to the pathological diagnosis of MVI, the lesions were divided into MVI (+ ) group and MVI (-) group. The indicators between the two groups were compared. All 183 lesions were put into the training set, and the prediction model with nomogram was constructed according to the risk factors of MVI selected by multivariate Logistic regression. The internal verification was carried out by ten-fold cross-validation method.Results:There were significant statistical differences in the following parameters between MVI (+ ) group ( n=109) and MVI (-) group ( n=74) (all P<0.05). These were cirrhosis, serological parameters (alpha-fetoprotein, albumin, total bilirubin), qualitative indexes of US (size, boundary, internal echo), qualitative indexes of CEUS (hyper/iso/hypovascularity of lesions in arterial phase, portal phase, and delayed phase compared with hepatic parenchyma), and quantitative indexes of EOB-MRI [post enhancement rate (post ratio) and gadolinium disodium rate (EOB ratio)] calculated mainly in terms of lesions and surrounding liver parenchyma in hepatobiliary phase and unenhanced T1 images). Finally, cirrhosis of patients, the size, boundary, internal echo of lesions in US; arterial phase (AP), portal phase (PP), post-vascular phase (PVP) features in CEUS; the EOB rate and post rate of EOB-MRI entered the prediction model of MVI. The training set exhibited good calibration and net gain rate. The areas under the ROC curve for the training set and the validation set were 0.981 and 0.961, respectively, while the diagnostic accuracy were 92.9% and 85.8%, respectively. Conclusions:The model constructed mainly by multimodality imaging methods can achieve favorable predictive performance for MVI, which provides valuable ideas for noninvasively predicting the incidence of MVI and optimizing the MVI-related treatment of MVI in HCC patients.

Content determination of five constituents in Shenfukang Ⅱ capsule by HPLC / 中国药房

OBJECTIVE To develop an HPLC method for the simultaneous dete rmination of morroniside ，loganin，paeoniflorin， salvianolic acid B and icariin in Shenfukang Ⅱ capsule. METHODS The determination was performed on Agilent 5 TC-C18 column with mobile phase consisted of acetonitrile- 0.1％ phosphate acid （gradient elution ）at the flow rate of 1 mL/min. The column temperature was 30 ℃，and detection wavelength was set at 240 nm. The sample size was 10 μL. RESULTS The linear range of morroniside，loganin，paeoniflorin，salvianolic acid B and icariin were 4.80-240.00，4.84-242.00，7.00-350.00，4.72-236.00 and 5.18-259.00 μg/mL（r≥0.999 8），respectively. RSDs of precision ，stability and reproducibility tests were all lower than 3％（n＝6）. Average recoveries were 97.22％-101.36％ with the RSDs of 1.19％-2.43％（n＝6）. The contents of above 5 components in 5 batches of samples were 2.019 3-2.360 0，1.624 2-1.847 1，5.637 7-6.828 0，5.015 9-5.717 0 and 1.208 8-1.754 6 mg/g，respectively. CONCLUSIONS The method is simple ，accurate and reproducible. It can improve the quality control level of Shenfukang Ⅱ capsule.

Diagnosis and treatment of hepatic artery thrombosis after adult orthotopic liver transplantation / 中华消化外科杂志

Objective:To investigate the diagnosis and treatment of hepatic artery thrombosis (HAT) after adult orthotopic liver transplantation.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 411 patients who underwent adult orthotopic liver transplantation in the First Affiliated Hospital of Xi ′an Jiaotong University from December 2011 to July 2018 were collected. There were 328 males and 83 females, aged from 21 to 66 years, with a median age of 46 years. Observation indicators: (1) incidence of HAT and its clinical characteristics; (2) diagnosis of HAT; (3) treatment of HAT; (4) follow-up. Follow-up using outpatient service, telephone interview or WeChat group communication was conducted to detect the incidence of biliary stricture and survival of patients up to August 2018. Measurement data with normal distribution were represented as Mean± SD, measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages. Survival rate was estimated using the Kaplan-Meier method. Results:(1) Incidence of HAT and its clinical characteristics: 11 of 411 patients had HAT after orthotopic liver transplantation with the incidence of 2.68%(11/411), including 10 males and 1 female, aged 44 years(range, 22-63 years). The time to occurrence of postoperative HAT was 4 days(range, 1-15 days). The etiologies of 11 patients included 6 cases of hepatitis B virus-related cirrhosis, 1 case of hapatitis related cirrhosis, 1 case of hepato-cellular carcinoma, 1 case of liver cirrhosis, 1 case of alcoholic hepatitis related cirrhosis, 1 case of wilson disease. All the 11 patients were ABO compatible. The cold ischemic time and warm ischemic time of donor liver were (316±89)minutes and (13±4)minutes, respectively. Type Ⅰ arterial anasto-mosis was conducted in 11 patients. The clinical manifestations included asymptomatic type in 10 patients and sepsis type in 1 patient. (2) Diagnosis of HAT: all the 11 patients were confirmed with HAT by endovascular angiography, including 7 cases showed no arterial flow under Color Doppler ultrasound, and contrast-enhanced ultrasound indicated HAT. Two patients showed increased hepatic artery resistance index under Color Doppler ultrasound, and contrast-enhanced ultrasound indicated 1 case of HAT and 1 case of anastomotic stenosis. One patient showed slow velocity of hepatic artery blood flow and low resistance index under color Doppler ultrasound, and contrast-enhanced ultrasound indicated HAT. One patient showed slight blood flow signals under Color Doppler ultrasound, and contrast-enhanced ultrasound indicated HAT. (3) Treatment of HAT: 11 patients received endovascular therapy. Six patients had HAT completely disappeared after thrombolytic therapy, 5 patients with residual thrombosis continued thrombolytic therapy with microcatheter urokinase. Six patients with complications were improved after symptomatic treatment. HAT completely disappeared after (6.7±2.6)days of treatment and the clinical success rate was 11/11. (4) Follow-up: 11 patients were followed up for 19-1 722 days, with a median follow-up time of 46 days. During the follow-up, 4 patients had biliary stricture and underwent stent implantation. Nine patients survived with 1-, 3-, 5-year overall survival rates of 75%, 75%, 75%, and 2 patients died.Conclusions:The incidence of HAT after adult orthotopic liver transplantation is low and clinical manifestations are atypical. Contrast enhanced ultrasound can improve diagnosis of suspected thrombosis. Endovascular therapy is safe and effective, which can significantly improve the blood flow of hepatic artery.

Prognostic value of preoperative red blood cell distribution width for hepatocellular carcinoma / 中华消化外科杂志

Objective:To investigate the prognostic value of preoperative red blood cell distribution width (RDW) for hepatocellular carcinoma (HCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 025 HCC patients who were admitted to three medical centers (586 in the First Affiliated Hospital of Xi'an Jiaotong University, 248 in the Second Affiliated Hospital of Xi'an Jiaotong University and 191 in the Qinghai University Affiliated Hospital) between April 2002 and August 2017 were collected. There were 809 males and 216 females, aged (54±11)years, with a range from 16 to 83 years. The average coefficient of variation of RDW (RDW-CV) of 1 025 patients was 14.3%. Of 1 025 patients, 347 cases had high RDW of RDW-CV >14.3%, and 678 had low RDW of RDW-CV ≤14.3%. Observation indicators: (1) clinico-pathological data of HCC patients; (2) influencing factors for prognosis of HCC patients; (3) follow-up and survival. (4) stratified analysis of independent influencing factors. Follow-up was performed by outpatient examination, telephone interview or internet interview to detect postoperative survival of patients up to October 2017. Measurment data with normal distribution were represented as Mean±SD, and measurment data with skewed distribution were described as M (range). Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test. The Graphpad Prism 7.0 was used to draw survival curves, and Log-rank test was used for survival analysis. Univariate and multivariate analyses were performed using the COX proportional hazard model. Results:(1) Clinicopathological data of HCC patients: cases with age ≤70 years or >70 years, cases without cirhhosis or with cirhhosis , cases of Child-Pugh grade A or Child-Pugh grade B or C, cases with the level of alpha fetoprotein (AFP) ≤200 μg/L or >200 μg/L, cases with single tumor or multiple tumors were 313, 34, 152, 186, 161, 53, 158, 143, 186, 109 for high RDW patients, versus 641, 37, 359, 310, 415, 48, 367, 227, 547, 131 for low RDW patients, respectively, showing significant differences in above indicators between the two groups ( χ2=6.709, 6.787, 23.906, 7.114, 34.375, P<0.05). (2) Influencing factors for prognosis of HCC patients: results of univariate analysis showed that age, Child-Pugh grade, AFP, RDW-CV, tumor diameter, the number of tumors were related factors for prognosis of patients ( hazard ratio=1.388, 1.432, 1.534, 1.455, 2.813, 1.505, 95% confidence interval as 1.004-1.920, 1.086-1.887, 1.263-1.864, 1.211-1.748, 2.293-3.450, 1.173-1.932, P<0.05 ). Results of multivariate analysis showed that age, RDW-CV, tumor diameter and the number of tumors were independent factors for prognosis of patients ( hazard ratio=1.020, 1.340, 2.427, 1.438, 95% confidence interval as 1.007-1.032, 1.027-1.749, 1.801-3.272, 1.057-1.956, P<0.05). (3) Follow-up and survival: 1 025 patients were followed up for 1-124 months, with a median follow-up time of 25 months. The median survival time was 23 months for high RDW patients, versus 44 months for low RDW patients, showing a significant difference in the overall survival between the two groups ( χ2=11.640, P<0.05). (4) Stratified analysis of independent influencing factors: the results of stratified analysis of 3 independent influencing factors including age, tumor diameter and the number of tumors showed that in the 954 patients with age ≤70 years, the median survival time was 25 months for high RDW patients, versus 48 months for low RDW patients, showing a significant difference in the overall survival between the two groups ( χ2=14.030, P<0.05). In the 71 patients with age >70 years, the median survival time was 11 months for high RDW patients, versus 29 months for low RDW patients, showing no significant difference in the overall survival between the two groups ( χ2=0.933, P>0.05). In the 459 patients with tumor diameter ≤5 cm, the median survival time was 44 months for high RDW patients, versus 76 months for low RDW patients, showing a significant difference in the overall survival between the two groups ( χ2=8.660, P<0.05). In the 487 patients with tumor diameter >5 cm, the median survival time was 14 months for high RDW patients, versus 18 months for low RDW patients, showing no significant difference in the overall survival between the two groups ( χ2=2.950, P>0.05). In the 733 patients with single tumor, the median survival time was 20 months for high RDW patients, versus 48 months for low RDW patients, showing a significant difference in the overall survival between the two groups ( χ2=13.530, P<0.05). In the 240 patients with multiple tumors, the median survival time was 15 months for high RDW patients, versus 20 months for low RDW patients, showing a significant difference in the overall survival between the two groups ( χ2=6.820, P<0.05). Conclusions:Preoperative RDW can be used as a predictive index for prognosis of HCC patients, and patients with high RDW have poorer prognosis. RDW have better predictive value in patients with age ≤70 years or tumor diameter ≤5 cm.

Surgical treatment and prognosis analysis of intrahepatic cholangiocarcinoma with different lymph node metastasis status / 国际外科学杂志

Objective@#To analyze the effects of different N stages, surgical treatment, lymph node dissection and combined chemoradiotherapy on the prognosis of intrahepatic cholangiocarcinoma (ICC).@*Methods@#The clinical data and follow-up results of 4 555 ICCs in the SEER database were retrospectively analyzed. Including 3 710 patients with N0 phase and 845 patients with N1, all patients included complete TNM staging information, survival time and survival status information, surgical related information and radiotherapy and chemotherapy treatment information. The survival curve was described by Kaplan-Meier method. The survival of 120 months was described. The hypothesis test was performed by Log-rank test. The overall prognosis of patients with different N-stage ICCs was observed. Different surgical methods, lymph nodes were removed, and postoperatively. The effect of chemoradiotherapy on the prognosis of patients with different N-stage ICC. Measurement data with skewed distribution were expressed as medians, and count data were expressed as percentages.@*Results@#The median survival time of N1 patients was 12 months while 15 months in N0 patients. In N0 patients, the median survival time was 8 months of no operation performed patients, 26 months of local tumor destruction patients, and 45-59 months of surgical treatment performed patients. In N1 patients, the survival time was 9 months, 26 months and 14-22 months of no operation performed, local tumor destruction and surgical treatment performed patients, respectively. In the N0 stage, the median survival time was 37 months for lymph node dissection not performed patients, and the median survival time for lymph node dissection patients was 46-55 months. In N1 patients, the median survival time was 26 months and 18-20 months for without or with lymph node dissection patients. In the N0 stage, the median survival time was 41-42 months for without chemo- or radio-therapy, and it was 43-46 months for with chemo- or radio-therapy patients. In the N1 stage, the median survival time 10-17 months and 23 months for without or with chemo- or radio-therapy patients.@*Conclusions@#The prognosis of patients with N1 in ICC is significantly worse than that in patients with N0. Surgery is an effective method for the treatment of ICC. At the same time, routine lymphadenectomy should be recommended. Patients with N1 are recommended for radiotherapy and chemotherapy.

Risk factors of portal vein system thrombosis after splenectomy in patients with portal hypertension / 中华普通外科杂志

Objective:To investigate the risk factors of portal vein system thrombosis (PVST) after portoazygous devascularization in patients with portal hypertension.Methods:Clinical data of 215 patients with portal hypertension treated by splenectomy at the Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi′an Jiaotong University from Jan 2012 to Dec 2017 were retrospectively analyzed. Univariate analysis of variance and Logistic regression were used to analyze the clinical risk factors that may lead to PVST.Results:The incidence of PVST was 43.7%(94/215). Univariate analysis of variance showed that the diameter of portal vein, the diameter of splenic vein, the thickness of spleen, laparoscopic or open surgery, and postoperative platelet count were correlated with postoperative PVST (all P<0.05). Logistic regression analysis showed that splenic vein diameter ( OR=3.137, 95% CI 1.391-7.076, P=0.006), splenic thickness ( OR=3.065, 95% CI 1.418-6.626, P=0.004) and postoperative platelet count ( OR=7.446, 95% CI 3.057-18.137, P=0.000) were independent risk factors for PVST in patients with portal hypertension. Conclusion:Postoperative PVST in patients with portal hypertension are more likely to develope when preoperative splenic vein ≥11 mm, splenic thickness ≥60 mm and platelet count ≥300×10 9/L on the 7th day after operation.

Efficacy and safety prediction of cephalosporins antibiotics combined with metronidazole for intra-abdominal infections: a Bayesian network meta analysis / 中华消化外科杂志

Objective:To predict the efficacy and safety of cephalosporins antibiotics combined with metronidazole for intra-abdominal infections using Bayesian network meta analysis.Methods:Databases including PubMed, Embase, the Cochrane Library, CNKI, Wanfang database, VIP database were searched for literatures from January 1990 to May 2018 with the key words of ( "intraabdominal infections" [MeSH Terms]) AND ( "Cephalosporins*" [MeSH Terms]) AND ( "randomized controlled trial" [MeSH Terms]),腹腔感染,继发性腹膜炎,腹腔脓肿,头孢. The randomized controlled trials (RCTs) about comparison of efficacy and safety between cephalosporins antibiotics combined with metronidazole versus other antibiotics for intra-abdominal infections were received and included. Experimental group included patients who received cephalosporins antibiotics combined with metronidazole for intra-abdominal infections, and control group included patients who received other antibiotics for intra-abdominal infections. The primary outcomes were the clinical cure rates, microbial clearance rate and incidence of serious adverse drug reactions. R 3.6.2 software random Bayesian model was used for meta analysis. The Markov Chain Monte Carlo was used for direct evaluation and indirect prediction. The tracing method, density plotting and leverage figure method were used to evaluate the model convergence and stability. No closed loop formed between intervention measures, so there was no need to evaluate consistency.Results:(1) Document retrieval: a total of 18 available RCTs were enrolled. There were 6 792 patients, including 3 402 in the experimental group, 3 390 in the control group. (2) Results of Bayesian network meta analysis. ① The clinical cure rates of the third generation cephalosporins+ metronidazole, carbapenems were significantly lower than the fourth generation cephalosporins+ metronidazole [ odds ratio ( OR)=0.46, 0.61, 95% confidence interval( CI) as 0.26-0.81, 0.38-0.97, P<0.05]. There was no significant difference in the clinical cure rate between the fifth generation cephalosporins+ metronidazole and carbapenems ( OR=1.03, 95% CI as 0.59-1.80, P>0.05). ② The microbial clearance rates of the fifth generation cephalosporins+ metronidazole, carbapenems were significantly lower than the fourth generation cephalosporins+ metronidazole ( OR=0.84, 0.41, 95% CI as 0.73-0.98, 0.23-0.74, P<0.05). There was no significant difference in the microbial clearance rate between the fifth generation cephalosporins+ metronidazole and carbapenems ( OR=0.76, 95% CI as 0.27-1.80, P>0.05). ③ The incidence of serious adverse drug reactions was significantly lower for the third generation cephalosporins+ metronidazole, the fourth generation cephalosporins antibiotics+ cetronidazole, the fifth generation cephalosporins+ metronidazole, carbapenems, quinolones+ metronidazole, and tigecycline than for quinolones ( OR=0.13, 0.13, 0.14, 0.13, 0.15, 0.13, 95% CI as 0.03-0.50, 0.02-0.98, 0.02-0.75, 0.02-0.59, 0.02-0.78, 0.02-0.57, P<0.05). Compared with carbapenems, the third generation cephalosporins+ metronidazole, the fourth generation cephalosporins+ metronidazole, the fifth generation cephalosporins+ metronidazole had no significant difference in the incidence of serious adverse drug reactions ( OR=0.96, 1.00, 1.10, 95% CI as 0.52-1.60, 0.31-3.50, 0.49-2.30, P>0.05). (3) Ranking of the efficacy and safety. ① The ranking list for clinical cure rates of different therapeutic regimens showed from high to low as quinolones+ metronidazole, the fourth generation cephalosporins+ metronidazole, synthetic penicillins, the second generation cephalosporins+ metronidazole, the fifth generation cephalosporins+ metronidazole, carbapenems, the third generation cephalosporins+ metronidazole, tigecycline, quinolones. The corresponding ranking probabilities of above regimens were 51.73%, 35.72%, 22.57%, 31.37%, 24.98%, 32.82%, 34.69%, 29.05%, 72.36%, respectively. ② The ranking list for microbial clearance rates of different therapeutic regimens showed from high to low as quinolones+ metronidazole, the fourth generation cephalosporins+ metronidazole, the second generation cephalosporins+ metronidazole, synthetic penicillins, the fifth generation cephalosporins+ metronidazole, carbapenems, the third generation cephalosporins+ metronidazole, tigecycline, quinolones. The corresponding ranking probabilities of above regimens were 89.62%, 77.01%, 38.60%, 20.94%, 26.26%, 26.39%, 22.22%, 20.19%, 62.55%, respectively. ③ The ranking list for incidence of serious adverse drug reactions of different therapeutic regimens showed from high to low as quinolones, quinolones+ metronidazole, the fifth generation cephalosporins+ metronidazole, carbapenems, the third generation cephalosporins+ metronidazole, tigecycline, the fourth generation cephalosporins+ metronidazole. The corresponding ranking probabilities of above regimens were 96.21%, 30.46%, 21.09%, 25.27%, 27.26%, 19.45%, 31.69%, respectively. Conclusion:In the treatment of middle- and low-risk intra-abdominal infections, it is recommended to empirically use cephalosporins+ metronidazole instead of carbapenems.

Surgical treatment and prognosis analysis of intrahepatic cholangiocarcinoma with different lymph node metastasis status / 国际外科学杂志

Objective To analyze the effects of different N stages,surgical treatment,lymph node dissection and combined chemoradiotherapy on the prognosis of intrahepatic cholangiocarcinoma (ICC).Methods The clinical data and follow-up results of 4 555 ICCs in the SEER database were retrospectively analyzed.Including 3 710 patients with N0 phase and 845 patients with N1,all patients included complete TNM staging information,survival time and survival status information,surgical related information and radiotherapy and chemotherapy treatment information.The survival curve was described by Kaplan-Meier method.The survival of 120 months was described.The hypothesis test was performed by Log-rank test.The overall prognosis of patients with different Nstage ICCs was observed.Different surgical methods,lymph nodes were removed,and postoperatively.The effect of chemoradiotherapy on the prognosis of patients with different N-stage ICC.Measurement data with skewed distribution were expressed as medians,and count data were expressed as percentages.Results The median survival time of N1 patients was 12 months while 15 months in N0 patients.In N0 patients,the median survival time was 8 months of no operation performed patients,26 months of local tumor destruction patients,and 45-59 months of surgical treatment performed patients.In N1 patients,the survival time was 9 months,26 months and 14-22 months of no operation performed,local tumor destruction and surgical treatment performed patients,respectively.In the N0 stage,the median survival time was 37 months for lymph node dissection not performed patients,and the median survival time for lymph node dissection patients was 46-55 months.In N1 patients,the median survival time was 26 months and 18-20 months for without or with lymph node dissection patients.In the N0 stage,the median survival time was 41-42 months for without chemo-or radio-therapy,and it was 43-46 months for with chemo-or radio-therapy patients.In the N1 stage,the median survival time 10-17 months and 23 months for without or with chemo-or radio-therapy patients.Conclusions The prognosis of patients with N1 in ICC is significantly worse than that in patients with N0.Surgery is an effective method for the treatment of ICC.At the same time,routine lymphadenectomy should be recommended.Patients with N1 are recommended for radiotherapy and chemotherapy.

Hot-spot mutant genes in bile tract tumors: A comprehensive analysis based on RRA method / 西安交通大学学报(医学版)

Objective: To analyze mutant genes in intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC) and gallbladder carcinoma (GBC) by robust rank aggregation (RRA) method to identify the differentially expressed mutant genes among these different types of bile tract tumors. Methods: We searched the Web of Knowledge, Scopus and PubMed databases, screened related references according to inclusion and exclusion criteria. Fourteen studies were included. We analyzed the mutant genes mentioned in each paper; used RRA method to identify hot-spot mutant genes in ICC, ECC and GBC; allocated the special mutant genes in bile tract tumors. Results: We confirmed that IDH1 (mutation frequency 16.9%) and KRAS (mutation frequency 15.7%) were hot-spot mutant genes in ICC. KRAS (mutation frequency 47.0%) and TP53 (mutation frequency 29.4%) were hot-spot mutant genes in ECC. TP53 (mutation frequency 36.8%) and KRAS (mutation frequency 18.4%) were hot-spot mutant genes in GBC. Furthermore, among the three kinds of bile tract tumors, IDH1 was identified as a special mutant gene in ICC. Conclusion: IDH1, KRAS and TP53 are hot-spot mutant genes in patients with bile tract tumors. Moreover, mutant KRAS is the common mutant gene in cholangiocarcinoma and IDH1 mutation may play a special role in ICC.

Clinical efficacy of splenectomy combined with coronary-caval shunt in treatment of portal hypertension / 中华消化外科杂志

Objective To investigate the clinical efficacy of splenectomy combined with coronary-caval shunt in treatment of portal hypertension (PHT).Methods The retrospective descriptive study was conducted.The clinical data of 21 patients with PHT who underwent splenectomy combined with coronary-caval shunt at the First Affiliated Hospital of Xi'an Jiaotong University from January 2001 to December 2015 were collected.Observation indicators included (1) operation situations,changes of pre-and post-operative portal hemodynamics including operation time and volume of intraoperative blood loss,diameter and blood flow velocity of portal vein (PV),gastric coronary vein and superior mesenteric vein (SMV).(2) Clinical indexes in perioperative period (before operation,at postoperative 1 week and 1 month):① blood routine test:the counts of red blood cell (RBC),white blood cell (WBC) and platelet (PLT),② liver function:Child-Pugh score,alanine transaminase (ALT),total bilirubin (TBil),albumin (Alb),extended time of prothrombin time (PT) and international normalized ratio (INR).(3) Follow-up:postoperative 1-,3-,5-year complications [upper gastrointestinal re-bleeding,peritoneal effusion,hepatic encephalopathy,hepatic failure,portal vein thrombosis (PVT) and anastomotic stoma thrombosis].The follow-up using outpatient examination and telephone interview was regularly conducted once every 3 months within postoperative 1 year and once every 6 months after postoperative 1 year up to March 2016 or end of follow-up (death).Measurement data with normal distribution were presented as x ± s.The comparison of different time-point was analyzed by the repeated measures ANOVA and Student t test.Measurement data with sknewed distribution were presented as M (range).Results (1) Operation situations and changes of pre-and post-operative portal hemodynamics:21 patients underwent successful splenectomy combined with coronary-caval shunt,including 19 receiving splenic vein bypass combined with anastomosis of gastric coronary vein and inferior vena cava and 2 receiving anastomosis of gastric coronary vein and inferior vena cava.Operation time,volume of intraoperative blood loss were (187 ± 33)minutes and (233 ± 114)mL.Diameter and blood flow velocity of PV,gastric coronary vein and SMV were (1.39±0.20)cm,(0.66±0.15)cm,(0.74±0.32)cm,(11.2±3.4)cm/s,(6.6± 1.3)cm/s,(7.0 ±2.2)cm/s before operation and (1.36 ±0.22)cm,(0.42 ±0.11)cm,(0.81 ±0.23)cm,(10.4 ± 2.5) cm/s,(8.2 ± 2.5) cm/s,(6.9 ± 2.4) cm/s after operation,respectively,showing no statistically significant difference in the diameter and blood flow velocity of PV and SMV before and after operation (t =0.46,-0.81,0.87,0.14,P ＞ 0.05)and with statistically significant differences in the diameter and blood flow velocity of gastric coronary vein before and after operation (t =5.9 1,-2.60,P ＜ 0.05).(2) Clinical indexes in perioperative period:① routine blood test:the counts of RBC,WBC and PLT were (2.70 ± 0.50) × 1012/L,(2.6 ±2.3) × 109/L,(55 ±28) × 109/L before operation and (3.10 ±0.60) × 1012/L,(2.8 ±2.0) × 109/L,(248 ± 182) × 109/L at postoperative 1 week and (3.70 ±0.20) × 1012/L,(6.2 ± 1.9) × 109/L,(457 ± 184) × 109/L at postoperative 1 month,respectively,with statistically significant differences (F =31.91,11.03,30.74,P ＜ 0.05).There were statistically significant differences in the counts of RBC and PLT between 1 week postoperatively and before operation (t =-2.35,-4.81,P ＜ 0.05) and between 1 month postoperatively and 1 week postoperatively (t =-4.35,-5.65,-3.71,P ＜ 0.05).② Liver function:Child-Pugh score,ALT,TBil,Alb,extended time of PT and INR were 6.3 ± 1.2,(23 ± 17) U/L,(28 ± 18) μmol/L,(31.1 ± 6.8) g/L,(4.8 ±2.1) s,1.40 ± 0.20 before operation and 6.2 ± 0.9,(44 ± 24) U/L,(26 ± 11) μmol/L,(35.0 ± 7.4) g/L,(3.4 ± 2.0) s,1.30 ± 0.20 at postoperative 1 week and 6.0 ± 0.6,(36 ± 22) U/L,(23 ± 8) μmol/L,(34.2 ± 2.2) g/L,(3.7 ± 3.0) s,1.50 ± 0.30 at postoperative 1 month,respectively,showing no statistically significant difference (F =1.97,2.60,1.18,1.45,P ＞0.05).There were statistically significant differences in the ALT and extended time of PT (F =7.97,4.37,P ＜ 0.05) and in the ALT and extended time of PT between 1 week postoperatively and before operation (t =3.23,2.21,P ＜ 0.05).(3) Follow-up:21 patients were followed up for 3-168 months with a median time of 37 months.During follow-up,3 patients were dead.One,1,2 patients were complicated with upper gastrointestinal re-bleeding at postoperative 1,3,5 years and received hemostatic therapy under endoscopy,and then 2 were dead.Three,2 and 2 patients had peritoneal effusion and were improved by symptomatic treatment.One patient had hepatic encephalopathy and hepatic failure at postoperative 5 years and was dead after conservative treatment.PVT and anastomotic stoma thrombosis at postoperative 1,3,5 years were detected in 2,2,1 and 2,1,1 patients,with anticoagulant therapy,and 1 patient received vascular recanalization.Conclusion Coronary-caval shunt is a highly selective portosystemic shunt,it can significantly down regulate the regional pressure while ensure the normal blood flow of liver and decrease the rate of rebleeding,hepatic encephalopathy and thrombosis,meanwhile,it might be a potential therapy in management of PHT.

Clinical and genetic investigation of a multi-generational Chinese family afflicted with Von Hippel-Lindau disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Von Hippel-Lindau (VHL) disease is a hereditary tumor disorder caused by mutations or deletions of the VHL gene. Few studies have documented the clinical phenotype and genetic basis of the occurrence of VHL disease in China. This study armed to present clinical and genetic analyses of VHL within a five-generation VHL family from Northwestern China, and summarize the VHL mutations and clinical characteristics of Chinese families with VHL according to previous studies.</p><p><b>METHODS</b>An epidemiological investigation of family members was done to collect the general information. A retrospective study of clinical VHL cases was launched to collect the relative clinical data. Genetic linkage and haplotype analysis were used to make sure the linkage of VHL to disease in this family. The VHL gene screening was performed by directly analyzing DNA sequence output. At last, we summarized the VHL gene mutation in China by the literature review.</p><p><b>RESULTS</b>A five-generation North-western Chinese family afflicted with VHL disease was traced in this research. The family consisted of 38 living family members, of whom nine were affected. The individuals afflicted with VHL exhibited multi-organ tumors that included pheochromocytomas (8), central nervous system hemangioblastomas (3), pancreatic endocrine tumors (2), pancreatic cysts (3), renal cysts (4), and paragangliomas (2). A linkage analysis resulted in a high maximal LOD score of 8.26 (theta = 0.0) for the marker D3S1263, which is in the same chromosome region as VHL. Sequence analysis resulted in the identification of a functional C>T transition mutation (c. 499 C>T, p.R167W) located in exon 3 of the 167 th codon of VHL. All affected individuals shared this mutation, whereas the unaffected family members and an additional 100 unrelated healthy individuals did not. To date, 49 mutations have been associated with this disease in Chinese populations. The most frequent VHL mutations in China are p.S65 W, p.N78 S, p.R161Q and p.R167 W.</p><p><b>CONCLUSIONS</b>The results supported the notion that the genomic sequence that corresponds to the 167 th residue of VHL is a mutational hotspot. Further research is needed to clarify the molecular role of VHL in the development of organ-specific tumors.</p>

Survival Analysis of Hepatocellular Carcinoma: A Comparison Between Young Patients and Aged Patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>To compare the clinicopathological features and prognosis between younger and aged patients with hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>We analyzed the outcome of 451 HCC patients underwent liver resection, transcatheter arterial chemoembolization and radiofrequency ablation, respectively. Then risk factors for aged and younger patients' survival were evaluated by multivariate analysis, respectively.</p><p><b>RESULTS</b>The patients who were older than 55 years old were defined as the older group. The overall survival for aged patients was significantly worse than those younger patients. The younger patients had similar liver functional reserve but more aggressive tumor factors than aged patients. Cox regression analysis showed that the elevated levels of aspartate aminotransferase (AST) (Wald χ2 = 3.963, P = 0.047, hazard ratio [HR] =1.453, 95% confidence interval [CI]: 1.006-2.098), lower albumin (Wald χ2 = 12.213, P < 0.001, HR = 1.982, 95% CI: 1.351-2.910), tumor size (Wald χ2 = 8.179, P = 0.004, HR = 1.841, 95% CI: 1.212-2.797), and higher alpha-fetoprotein level (Wald χ2 = 4.044, P = 0.044, HR = 1.465, 95% CI: 1.010-2.126) were independent prognostic factors for aged patients, while only elevated levels of AST (Wald χ2 = 14.491, P < 0.001, HR = 2.285, 95% CI: 1.493-3.496) and tumor size (Wald χ2 = 21.662, P < 0.001, HR = 2.928, 95% CI: 1.863-4.604) were independent prognostic factors for younger patients.</p><p><b>CONCLUSIONS</b>Age is a risk factor to determine the prognosis of patients with HCC. Aged patients who have good liver functional reserve are still encouraged to receive curative therapy.</p>

Cisplatin induces cell cycle arrest and senescence via upregulating P53 and P21 expression in HepG2 cells / 南方医科大学学报

<p><b>OBJECTIVE</b>Cellular senescence as one of the important steps against tumor is observed in many cancer patients receiving chemotherapy and is related to chemotherapeutic response. To investigate the effect of cisplatin on hepatocellular carcinoma, we treated HepG2 cells exhibiting wild-type TP53 with gradient concentrations of cisplatin.</p><p><b>METHODS</b>The inhibitory effects of cisplatin on human hepatoma HepG2 cells were detected by MTT assay and colony formation test. The changes in cell cycle were analyzed by flow cytometry, and cellular senescence was detected with senescence associated β-galactosidase (SA β-gal) staining. The relative mRNA expression levels of TP53, P21 and P19 was estimated using semi-quantitative real-time RT-PCR, and the protein expressions of P53 and P21 were detected using Western blotting.</p><p><b>RESULTS</b>Cisplatin induced irreversible proliferation inhibition and G1 phase arrest of HepG2 cells. Elevated levels of senescence-associated β-galactosidase was observed in HepG2 cells exposed to low doses of cisplatin. P19 expression immediately increased following cisplatin exposure and reached the maximum level at 48 h, followed then by a rapid decrease to the baseline level, whereas the expressions levels of TP53 and P21 mRNA increased continuously. Western blotting confirmed P53 and P21 expression changes similar to their mRNA expressions during cisplatin-induced cellular senescence in HepG2 cells.</p><p><b>CONCLUSION</b>Our results revealed a functional link between cisplatin and hepatocellular senescence. Cellular senescence induced by cisplatin as a stabile senescent cellular model can be used for further research.</p>

Inflammation: a key factor of gallbladder cancer / 中华肝胆外科杂志

Previous studies have suggested that various kinds of inflammatory factors can influence the formation and development of tumor cells.Researche has shown that gallbladder cancer is closely linked with local inflammation,which is a risk factor for the development of gallbladder cancer.It is widely known that cholecystitis is closely correlated with gallstones,and that bile obtained from patients with gallbladder cancer contains a large variety of bacteria,such as Salmonella typhi,Helicobacter,and Escherichia coli.It is proposed that the gallbladder may be the result of the joint action of inflammation with the bacterial flora.Similarly,the inflammatory “tumor infiltrating lymphocyte” (TIL)can be observed in the tumor and its surrounding tissues,and may also play a role in tumor growth and metastasis.However,detailed mechanisms about the relationship between inflammation and gallbladder cancer is still not clear.No specific anti-inflammatory drugs for gallbladder cancer have been developed. In the near future,anti inflammatory drugs may play a more important role in gallbladder cancer prevention and treatment.

Dual-phase scanning characteristics of multislice spiral CT for acute myocardial infarction / 第二军医大学学报

Objective: To analyze the characteristics of multislice spiral computed tomography (CT) for acute myocardial infarction. Methods: The anterior descending coronary arteries of 6 pigs were ligated at the 1/3 distal end to establish acute myocardial infarction model without reperfusion. Dual multislice spiral CT scanning was performed in all animals and the CT characteristics were analyzed. Results: Acute myocardial infarction model was successfully established in all 6 animals. Myocardial perfusion deficits were detected during early phase scanning; the area of deficits were significantly decreased during late phase scanning (13.52 ± 5.22% vs 9.07 ± 3.47% P = 0.004), with a mean decrease of 32.14%. CT value of different myocardial varied at different scanning times: the values of LV cavity decreased from (586 ± 111) HU to (294±53) HU (P = 0.001), that of the normal myocardial area decreased from (247±54) HU to (132±25) HU (P = 0.001); the values of the perfusion deficit regions were not significantly changed ([42 ± 14] HU vs [29 ± 23] HU, P = 0.289). During late phase scanning, CT value around residual perfusion deficit was higher than that of normal myocardium ([156±21] HU vs [132±25] HU, P = 0.004). Conclusion: The dual-phase MSCT characteristics of AMI include early perfusion deficits, late enhancement and residual perfusion deficits. Early phase scanning may overestimate the infarction area.

Common syndrome factors of traditional Chinese medicine in chronic renal failure based on the questionnaire investigation among experts / 中西医结合学报

To screen common traditional Chinese medicine (TCM) syndrome factors of chronic renal failure (CRF) via questionnaire investigation among experts.

Effects of Apelin-13 on rat myocardial ischemia-reperfusion injury in vivo and its signal transduction pathway / 上海第二医科大学学报

Objective To investigate the role of apelin-13, a vasoactive peptide, in rat myocardial ischemia-reperfusion injury in vivo and explore its signal transduction pathway. Methods Rats were randomly divided into control group (n=10) and Apelin-13 group (n=15), and in vivo models of rat myocardial ischemia-reperfusion injury were established. Normal saline (control group) or Apelin-13 (Apelin-13 group) was administered intravenously 5 min before reperfusion. TTC and Evan's blue staining were used to determine the infarction size (IS) and area at risk (AAR), apoptotic cells were quantified by TUNEL method, and the expression of ERK1/2 was determined by Western blotting. Results IS/AAR and apoptosis index of Apelin-13 group were significantly lower than those in control group [(38.33±12.95) % vs (52.61±11.00)% and (0.21±0.02) vs (0.31±0.05)](P <0.05). The expression of p-ERK1/2 in Apelin-13 group was significantly increased than that in control group [(1.15±0.16) vs (0.63±0.07)](P < 0.05). Conclusion Apelin-13 may protect rat hearts from in vivo ischemia-reperfusion injury, reduce infarction size and attenuate myocardial apoptosis, which may be mediated by the activation of ERK1/2 MAPK signal transduction pathway.

Dual-phase contrast-enhancement multislice computed tomography imaging in assessment of acute myocardial infarction-reperfusion injury / 上海第二医科大学学报

Objective To explore the value of dual-phase contrast-enhancement multislice computed tomography (MSCT) in the assessment of acute myocardial infarction volume and perfusion in porcine models. Methods The distal left anterior descending coronary arteries of 5 pigs were balloon-occluded for 90 min and followed by reperfusion. MSCT was performed 1 min (early phase) and 5 min (delayed phase) after administration bolus of 100 mL of iodinated contrast material 30 min after reperfusion. On the same day, hearts were excised, sectioned in 8 mm short-axis slices, and stained with TTC. Infarction volume was defined as the sum of the hyper-enhanced area and surrounding hypo-enhanced area in all slices on delay enhanced phase of MSCT and the TTC-negative area on TTC staining slices. Infarction volume was expressed as percentage of total slice volume. Results Acute infarction detected by MSCT was characterized by early myocardial perfasion defects in the early phase of the contrast bolus (early defects) with surrounding residual defects and late enhancement observed in the late phase. Mean CT attenuation value of early defects was significantly different from CT attenuation value of remote myocardium [(213±55)HU vs (304±30)HU](P < 0.05), CT attenuation values of residual defects and late enhancement were also significantly different from those of remote myocardium [(360±75) HU vs (90±37) HU and (152±23) HU vs (190±37) HU, repectively](P < 0.01, P < 0.05). The mean infarction volume was (8.9± 1.0)% on MSCT and (9.2±1.4)% on TTC pathology images. The infarction volume assessed by MSCT compared well with TTC staining slices. Conclusion Acute reperfused myocardial infarction zone has specific enhancement pattens different to remote normal zone on dual phase MDCT, which is in good agreement with in vivo Trc pathology in the assessment of acute reperfused myocardial infarction shortly offer reperfusion.

A perspective of developing syndrome diagnostic criteria based on syndrome factors and combination of disease in modern medicine system and syndrome in traditional Chinese medicine system / 中西医结合学报

Syndrome differentiation treatment is the traditional model of diagnosis and treatment of diseases in traditional Chinese medicine (TCM). To establish scientific diagnostic criteria of TCM syndrome is one of the key points in TCM study. In this paper, the basic models of the relevant diagnostic criteria of TCM syndrome and existed problems were reviewed. The authors pointed out the advantages of establishing diagnostic criteria of TCM syndrome based on TCM syndrome factors and combination of disease in Western medicine system and TCM syndrome, in which not only the characteristics of the disease in Western medicine were considered, but also the complexity and flexibility of syndrome identification and convenient application in clinical practice were resolved. The basic model and frame of the above diagnostic criteria and the procedures and methods used in developing the diagnostic criteria were also described and discussed.

Molecular Mechanism of Hyaluronan Biosynthesis in Streptococci and Construction of Engineering Strains / 中国生物工程杂志

Hyaluronic acid(HA)is a linear polysaccharide chain composed of alternating ?-1,4-glucuronic acid(GlcA)and ?-1,3-N-acetylglucosamine(GlcNAc)moieties.Construction of engineering strain has become the prevailing strategy for increasing yield and improving its quality,especially the molecular weight.Here the molecular mechanism of HA biosynthesis in Streptococcus strains was reviewed,involving fermentation strains,operon structure,crucial enzyme and construction of engineering strains.In addition,the prevalent problems in HA fermentation production were also discussed and the protocols were tentatively put forward for the upcoming research and industrial production.