1.Stromal Cell-Derived Factor 1α Inhibits Chondrocyte Apoptosis and Promotes Autophagy Through the Akt Signaling Pathway
Jiazhou LI ; Jing XIE ; Xuedong ZHOU
Journal of Sichuan University (Medical Sciences) 2024;55(1):53-59
Objective To investigate the effects of stromal cell-derived factor 1α(SDF-1α)on the apoptosis and autophagy of chondrocytes and the underlying mechanisms.Methods Chondrocytes were isolated from the knee joints of neonatal mice.The chondrocytes were then stimulated with 0(the control group),50,100,and 200 ng/mL of SDF-1α.CCK-8 assay was performed to determine the effects of SDF-1α stimulation for 24 h,48 h,and 72 h on the viability of the chondrocytes.Wound healing assay was conducted to determine the effects of SDF-1α stimulation for 12 h and 24 h on chondrocyte migration.The changes in the expression of Akt signaling pathway proteins in chondrocytes were determined by Western blot assay.Chondrocytes were stimulated with 0(the control group)and 200 ng/mL of SDF-1α.Flow cytometry was performed to determine the effect of SDF-1α on the apoptosis of chondrocytes.Transmission electron microscope was used to examine the effect of SDF-1α on chondrocyte autophagy.Immunofluorescence staining assays were performed to visualize the differences in p-Akt expression and distribution in chondrocytes treated with SDF-1α.Results Compared with the control group,findings for the experimental groups showed that SDF-1α at the concentrations of 50,100,and 200 ng/mL did not decrease chondrocyte activity at any time point(P<0.01)and it consistently promoted chondrocyte migration at 24 h(P<0.05).Western blot results revealed that,in comparison to the control group,SDF-1α at concentrations of 50,100,and 200 ng/mL significantly up-regulated the protein expression of p-Akt in chondrocytes,while no significant difference in Akt expression was observed.Flow cytometry demonstrated that SDF-1α could inhibit chondrocyte apoptosis(P<0.05)and transmission electron microscopic observation showed that SDF-1α promoted chondrocyte autophagy(P<0.05).Immunofluorescence staining showed that the expression of p-Akt in chondrocytes was concentrated in the perinuclear area of the cells and this expression was further enhanced in the perinuclear area of the chondrocytes after treatment with SDF-1α.Conclusion SDF-1α inhibits chondrocyte apoptosis and promotes chondrocyte migration and autophagy through activating the Akt signaling pathway.
2.Establishment and evaluation of a novel and non-invasive diagnostic model on cirrhotic patients
Rongyun MAI ; Jiazhou YE ; Jie ZENG ; Tao BAI ; Jie CHEN ; Shan HUANG ; Lequn LI ; Feixiang WU ; Guobin WU
Chinese Journal of Hepatobiliary Surgery 2019;25(4):254-258
Objective To establish and evaluate a novel and non-invasive diagnostic model using routine laboratory serological indexes in cirrhotic patients.Methods A retrospective study was conducted on 1044 consecutive patients with hepatocellular carcinoma (HCC) treated by hepatectomy in the Affiliated Tumor Hospital of Guangxi Medical University from September 2013 to December 2016.These patients were divided into a training cohort (n =783) and a validation cohort (n =261) using the 3 ∶ 1 matching principle.Logistic regression analysis was used to identify independent risk factors related to occurrence of cirrhosis in the training cohort,and then a PPH score was established.The accuracy of the model in predicting cirrhosis in two groups was evaluated respectively by the area under the receiver operating characteristic curve (AUC) and goodness of fit,and compared with the following commonly used predictive systems:the model for endstage liver disease (MELD) score,fibrosis index based on 4 factor score (FIB-4),Forns score and aspartate aminotransferase to platelet ratio index score (APRI).Results Univariate and multivariate Logistic regression analysis in the training cohort showed prothrombin time,platelet count and hepatitis B surface antigen positivity were closely related to occurrence of cirrhosis.The accuracy of the PPH score (AUC =0.705) in diagnosing cirrhosis in the training cohort was significantly better than the MELD score (AUC =0.557),APRI score (AUC =0.598),FIB-4 score (AUC =0.597) and Forns score (AUC =0.665).Similar results were obtained in the validation cohort (AUC:0.702 vs 0.554 vs 0.624 vs 0.634 vs 0.580).The goodness of fit indicated that there was no significant difference between the actual and predicted values of cirrhosis in the two cohorts,and the model was in good agreement.Conclusions A novel and non-invasive model for the diagnosis of cirrhosis was successfully established.The accuracy of this model in diagnosing cirrhosis was better than the MELD,APRI,Fib-4 and Forns scores.This model has significance in guiding clinical treatment decision in HCC patients with cirrhosis.
3. Clinical applicaton of three-dimensional visualization technology in hepatectomy of complex hepatocellular carcinoma
Meng WEI ; Jiazhou YE ; Tao BAI ; Jie CHEN ; Rongyun MAI ; Yumeng PENG ; Lianda ZHANG ; Zhiwei CHEN ; Lequn LI ; Feixiang WU
Chinese Journal of Hepatobiliary Surgery 2019;25(9):653-655
Objective:
To study the clinical application of three-dimensional (3D) visualization technology in liver resection of complicated liver cancer.
Methods:
A retrospective analysis of 28 patients with complicated liver cancer treated from June 2017 to June 2018 in the Department of Hepatobiliary Surgery, the Affiliated Tumor Hospital of Guangxi Medical University. There were 26 males and 2 females, aged (46±10) years old. A treatment plan on how to perform liver resection for these patients was developed under the guidance of 3D visualization technology. The actual surgical procedures, operation time, intraoperative blood loss, and postoperative complications were documented. The virtual resected liver volume was compared with the actual resected liver volume. The virtual surgical resection margin was also compared with the actual surgical resection margin.
Results:
All the 28 patients with complicated liver cancer completed the 3D visualization analysis with the location, shape and quantity of tumor being clearly shown. Of the 27 patients who underwent liver resection, 13 underwent anatomical hepatectomy, and 14 underwent non-anatomical hepatectomy. The operation time ranged from 145 to 350 min (median 240 min). The intraoperative blood loss ranged from 100 to 1 500 ml (median 300 ml). The incisional wound healed slowly in 4 patients, pleural effusion developed in 8 patients, and ascites in 2 patients. There were no significant differences in the virtual resected liver volume compared with the actual resected liver volume (
4.Surgical effect analysis of hepatocellular carcinoma with different lymphovascular invasion
Teng WEI ; Jiazhou YE ; Yebin PANG ; Liang MA ; Zhiming ZHANG ; Weiping YUAN ; Bangde XIANG ; Lequn LI
Chinese Journal of Digestive Surgery 2018;17(3):285-291
Objective To compare the clinical features and surgical outcomes of hepatocellular carcinoma (HCC) combined with portal venous tumor thrombus (PVTT) and hepatic venous tumor thrombus (HVTT) or bile duct tumor thrombi (BDTT),and analyze the effects of different tumor thrombus (TT) types and different surgical methods for TT on prognosis.Methods The retrospective cross-sectional study was conducted.The clinical data of 220 HCC patients with lymphovascular invasion (LVI) who were admitted to the Affiliated Cancer Hospital of Guangxi Medical University between January 2004 and December 2014 were collected.Of 220 patients,140 were combined with PVTT,36 with HVTT and 44 with BDTT.According to patients' conditions,they underwent tumor and TT resection,and tumor resection + TT removal or single TT removal.Observation indicators:(1) comparisons of clinical features of HCC patients with PVTT or HVTT or BDTT;(2) surgical and postoperative situations;(3) follow-up and survival.Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival up to December 2015.Measurement data with normal distribution were represented as (x)±s.Comparisons among 3 indicators were analyzed using the one-way ANOVA,and comparisons between 2 indicators were analyzed using the t test.Comparisons of count data were analyzed using the chi-square test.The survival curve and rate were respectively drawn and calculated by the Kaplan-Meier method,and the Log-rank test was used for survival analysis.Results (1) Comparisons of clinical features of HCC patients with PVTT or HVTT or BDTT:number of patients with Child-pugh A,Child-pugh B and peritoneal effusion,tumor diameter and cases with tumor capsule were respectively detected in 133,7,23,(10±4)cm,91 in HCC patients with PVTT and 35,1,4,(9±4)cm,27 in HCC patients with HVTT and 35,9,16,(6±4)cm,15 in HCC patients with BDTT,with statistically significant differences (x2 =12.693,10.408,F=11.300,x2 =17.188,P< 0.05).(2) Surgical and postoperative situations:of 140 HCC patients with PVTT,51 underwent tumor and PVTT resection,89 underwent tumor resection + PVTT removal through incising portal vein;68 received postoperative transcatheter arterial chemoembolization (TACE).Thirty-six HCC patients with HVTT underwent tumor and HVTT resection;24 received postoperative TACE.Of 44 HCC patients with BDTT,23 underwent tumor and BDTT resection,21 underwent tumor resection + BDTT removal through incising common bile duct;29 received postoperative TACE.(3) Follow-up and survival:① 220 patients were followed up for 1-73 months,with a median time of 12 months.The median survival time,1-,3-and 5-year survival rates were respectively 12 months,48.2%,25.0%,15.4% in 140 HCC patients with PVTT and 28 months,77.1%,45.6%,24.5% in 36 HCC patients with HVTT and 36 months,88.6%,48.3%,24.6% in 44 HCC patients with BDTT,with a statistically significant difference in survival (x2 =13.316,P<0.05).② Of 140 HCC patients with PVTT,49 were in type Ⅰ PVTT,and median survival time,1-,3-and 5-year survival rates were respectively 20 months,60.3%,32.6% and 17.1%;70 were in type Ⅱ PVTT,and median survival time,1-,3-and 5-year survival rates were respectively 13 months,51.4%,26.0% and 17.3%;21 were in type Ⅲ PVTT,and median survival time,1-,3-and 5-year survival rates were respectively 7 months,9.5%,4.8% and 0,showing a statistically significant difference in survival (x2=18.102,P<0.05).The median survival time,1-,3-and 5-year survival rates were respectively 21 months,72.5%,42.5%,26.2% in 51 patients undergoing tumor and TT resection and 9 months,40%,14.4%,0 in 89 patients undergoing tumor resection + PVTT removal through incising portal vein,showing a statistically significant difference in survival (x2=24.098,P<0.05).③ Of 36 HCC patients with HVTT,17 were detected in right HVTT,and median survival time,1-,3-and 5-year survival rates were respectively 14 months,64.7%,20.2% and 0;10 were detected in left HVTT,and median survival time,1-,3-and 5-year survival rates were respectively 53 months,80.0%,70.0% and 38.9%;9 were detected in middle HVTT,and median survival time,1-,3-and 5-year survival rates were respectively 40 months,88.9%,61.0% and 30.5%;showing no statistically significant difference in survival (x2 =5.951,P>0.05).④ Of 44 HCC patients with BDTT,24,6 and 14 were respectively detected in type Ⅰ,Ⅱ and Ⅲ BDTTs,and median survival time,1-,3-and 5-year survival rates were respectively 38 months,87.5%,60.4%,34.9% in type Ⅰ BDTT patients and 26 months,83.3%,16.7%,0 in type Ⅱ BDTT patients and 35 months,78.6%,50.0%,21.4% in type Ⅲ BDTT patients,showing no statistically significant difference in survival (x2 =5.312,P>0.05).Of 44 patients,median survival time,1-,3-and 5-year survival rates were respectively 38 months,91.3%,59.5%,34.3% in 23 patients undergoing tumor and TT resection and 26 months,85.7%,35.7%,15.3% in 21 patients undergoing tumor resection + TT removal through incising common bile duct,showing no statistically significant difference in survival (x2 =2.071,P>0.05).Conclusions HCC patients with PVTT have larger tumor diameter and worse liver dysfunction,and are prone to peritoneal effusion.HCC patients with different LVI undergo surgery.There is better prognosis in HCC patients with BDTT,and good prognosis in patients with HVTT,while poorer prognosis in patients with PVTT.The postoperative survival of HCC patients with PVTT is associated with TT type,and patients will have better prognosis after tumor resection + TT removal if TT type is confirmed earlier.The postoperative survival of HCC patients with BDTT is not associated with TT type,tumor resection + TT removal maybe prolong postoperative survival time.
5.Clinical significance of serum prealbumin-bilirubin score (PALBI) in predicting posthepatectomy liver failure in patients with HBV-related hepatocellular carcinoma
Rongyun MAI ; Jiazhou YE ; Jie ZENG ; Xianmao SHI ; Zhongrong LONG ; Jinwu LIU ; Zhiwei CHEN ; Shan HUANG ; Fang LIAN ; Lequn LI ; Feixiang WU ; Guobin WU
Chinese Journal of Hepatobiliary Surgery 2018;24(11):737-741
Objective To study the value of serum prealbumin-bilirubin score (PALBI) in predicting posthepatectomy liver failure (PHLF) for patients with HBV related hepatocellular carcinoma (HCC).Methods A retrospective study was conducted on 919 HBV-related HCC patients who underwent hepatectomy from September 2013 to December 2016 at the Affiliated Tumor Hospital of Guangxi Medical University.These patients were divided into a training cohort (n =689) and a validation cohort (n =230) using the 3 ∶ 1 matching principle.The training cohort was divided into the control group (n=546) and the PHLF group (n=143) according to whether PHLF occurred.The multivariate logistic regression model was used to analyze the factors related to PHLF in the training cohort,and then the PALBI score was established.The ability of the PALBI score to predict PHLF was evaluated by the area under the receiver operating characteristic curve (AUC) and compared with the Child-Pugh,model for end-stage liver disease (MELD),and albumin-bilirubin (ALBI) scores.Results Univariate and multivariate logistic regression analyses showed the factors including HBV-DNA≥ 103 IU/ml,total bilirubin,prealbumin,platelet count,AST,prothrombin time,intraoperative blood loss ≥400 ml and major liver resection were closely related to PHLF.The ability of the PALBI score (AUC =0.733) to predict PHLF preoperatively was superior to the ChildPugh score (AUC =0.562),the MELD score (AUC =0.652) and the ALBI score (AUC =0.683) in the entire training cohort.Similar results were obtained in the entire validation cohort (AUC:0.752 vs.0.599 vs.0.641 vs.0.678).To eliminate the effect of a small residual liver volume on PHLF,the ability of each of these scores in the training and validation cohorts to predict PHLF was calculated respectively in these 2 cohorts of patients who underwent only minor liver resection,and similar results were obtained.Conclusion The PALBI score was significantly superior to the Child-Pugh,MELD and ALBI scores in predicting PHLF in patients with HBV-related HCC who underwent liver resection.The PALBI score is a simple,non-invasive and reliable novel model in predicting PHLF.
6.The impact of anatomical resection for hepatocellular carcinoma with microvascular invasion on early tumor recurrence
Zihui LI ; Jiazhou YE ; Jie CHEN ; Tao BAI ; Zongquan WU ; Ling ZOU ; Shanpo HUANG ; Lequn LI ; Feixiang WU
Chinese Journal of Hepatobiliary Surgery 2018;24(1):18-22
Objective To study the impact of anatomical resection (AR) for hepatocellular carcinoma with microvascular invasion on early tumor recurrence.Methods 178 consecutive patients with solitary hepatocellular carcinoma who underwent liver resection at the Affiliated Tumor Hospital of Guangxi Medical University from January 2012 to December 2015 were retrospectively studied.These patients were divided into four groups according the types of resection (anatomical resection AR or non-anatomical resection NAR) and the surgical margins (narrow or wide margin).All the patients were followed up until the tumor recurred or two years after surgery.The recurrence-free survival and the types of recurrence for the 4 different groups were compared.Results The 6 months,1-,2-year disease-free survival rates in the AR (n =55) and NAR groups (n =123) were 87.0%,79.2%,74.5% and 78.5%,61.3%,45.7 %,respectively,(P < 0.05).Through pair-wise comparisons of the four groups,there were no significant differences in early recurrence between the narrow surgical margin group and the wide surgical margin group,regardless of the types of surgery.The early recurrence rates of the AR groups were significantly lower than that of the NAR groups,regardless of the widths of the surgical margins.Multivariate analysis showed that AR was a protective factor of early recurrence (HR =0.417,95% CI 0.229 ~ 0.761).Further analysis of the recurrence patterns of AR and NAR showed that the recurrence types were mainly sohtary for AR (solitary,61.5%;multiple 30.8%) and multiple recurrence for NAR (solitary,32.2%;multiple 61.0%).Conclusion AR improved early recurrence-free survival of patients with microvascular invasion.
7.Evaluation of volumetric modulated arc therapy planning for rectal cancer based on Auto-Planning
Kaixuan LI ; Xi CHANG ; Jiazhou WANG ; Zhi CHEN ; Junqi WANG ; Zhen ZHANG ; Juefeng WAN ; Weigang HU
Chinese Journal of Radiation Oncology 2017;26(11):1308-1312
Objective To determine whether Auto-Planning-based volumetric modulated radiotherapy(Auto-VMAT)planning can improve planning efficiency without compromising plan quality compared with current manual trial-and-error-based volumetric modulated arc therapy(Manual-VMAT) planning for patients with rectal cancer. Methods Ten patients with stage Ⅱ-Ⅲ rectal cancer who underwent Dixon surgery were enrolled as subjects. The Pinnacle 9.10 planning system was used to design Manual-VMAT and Auto-VMAT plans. Dose distribution,homogeneity index(HI),conformity index(CI), D meanvalues of different organs at risk or dose-volume histogram of regions of interest,total planning time, and manual planning time were compared between the two plans. The differences were analyzed by paired t test. Results Dosimetric prescriptions were achieved in both plans. There were no significant differences in HI or CI between the Auto-VMAT plans and the Manual-VMAT plans(0.058 vs. 0.058, P=0.972;0.921 vs. 0.940,P=0.115). Compared with the Manual-VMAT plans,the V 40,D mean,and D 50%of the bladder were significantly reduced by 25.6%, 11.5%, and 8.9%, respectively, in the Auto-VMAT plans(P=0.004,0.016,0.001);the V 40,D mean,and D 50%of the small intestine were also significantly reduced by 12.1%,5.4%,and 6.8%,respectively,in the Auto-VMAT plans(P=0.023,0.001,0.001);the V 30, D mean,and D 50%of the left and right femoral heads were slightly reduced in the Auto-VMAT plans. The Auto-VMAT plans had significantly longer total planning time but significantly shorter manual planning time than the Manual-VMAT plans(50.38 vs. 36.81 min, P= 0.000;4.47 vs. 16.94 min, P= 0.000). Conclusions Compared with the Manual-VMAT plans, the Auto-VMAT plans have substantially shorter manual planning time and improved planning efficiency.
8.Application of radiomics approach for decoding normal liver features and predicting chemotherapy-associated liver injury:A preliminary study
Fan XIA ; Panpan HU ; Jiazhou WANG ; Weigang HU ; Guichao LI ; Zhen ZHANG
China Oncology 2016;26(6):521-526
Background and purpose:Radiomics refers to the comprehensive quantification of human tissues through assessing a large number of quantitative image features. Radiomics approach is used to decode tumor phenotypes and predict treatment outcomes. Here we present a study investigating radiomic analysis to assess normal liver features and predict chemotherapy-associated liver injury.Methods:Gastric cancer patients treated with surgery and adjuvant chemotherapy were enrolled in this study retrospectively. CT images were obtained before chemotherapy. The whole liver organ was delineated by radiation oncologists. Images were extracted and filtered by radiomic approach to extract radiomic features. Clustering was performed to reveal clusters of patients with similar radiomic expression patterns. Chi-squared tests were used to assess the association of radiomic data with clinical data and chemotherapy-related liver injury.Results:Radiomic features of 73 patients were clustered into two clusters. A significant association with gender (P=0.004, chi-squared test) was observed, where in male showed a higher presence in cluster Ⅰ. Incidence of abnormal liver function after chemotherapy was 48.7% in cluster I and 67.6% in cluster Ⅱ, respectively (Δ=18.9%). Clinical data including age, gender, chemotherapy modality, number of chemotherapy cycles, HBV infection history, HBs-antigen presence were not associated with liver function abnormalities after chemotherapy. Accuracy of radiomic analysis to predict liver injury is 0.59.Conclusion:Radiomic approach revealed different imaging features of liver between men and women. It could help to predict chemotherapy-associated liver injury. It is feasible to use radiomics approach to decode normal liver features and predict treatment-associated liver injury.
9.Dosimetric study of simpliifed intensity-modulated radiation therapy for nasopharyngeal carcinoma
Kaixuan LI ; Jiazhou WANG ; Rui JIANG ; Weigang HU
China Oncology 2015;(12):978-982
Background and purpose:Radiotherapy has been the preferred method for the treatment of naso-pharyngeal carcinoma (NPC). The aim of this paper was to compare the dosimetric differences in target volume and organ at risk between simpliifed intensity-modulated radiation therapy (sIMRT) and intensity-modulated radiation therapy (IMRT) in nasopharyngeal carcinoma.Methods:Treatment plans for ten NPC cases were designed with the same dose prescription and objective by means of IMRT and sIMRT respectively. Compare:(1) Plan dosimetric dis-tribution, conformity index (CI) and homogeneity index (HI) of the targets, the dosimetric parameters of organ at risk (OAR); (2)The total monitor units (MU) and the total segments.Results:The CI and HI of the planning gross tumor volume(PGTV) were 0.647 and 0.057 (IMRT), 0.633 and 0.071 (sIMRT), respectively (t=2.14,P=0.062;t=-6.21, P=0.000). Compared to IMRT, sIMRT had less inferior target homogeneity. However both treatment plans could achieve the clinical dosimetric demands. There was no signiifcant difference between IMRT and sIMRT in protecting OAR (t=-0.51-2.22,P=0.053-0.621). The sIMRT plan was better than IMRT plan in total MU and total segments. Conclusion:sIMRT is slightly inferior to IMRT in terms of target homogeneity, with similar target conformity and OAR dosimetric parameters. The sIMRT plan can reduce total monitor units and total segments. Thus it provides a clinical solution with high effciency for radiotherapy center with a large number of patients.
10.Impact of treatment strategies on patients with hepatocellular carcinoma of less than 10 cm but with portal vein tumor thrombus
Liang MA ; Jiazhou YE ; Bangde XIANG ; Feixiang WU ; Yinnong ZHAO ; Lequn LI
Chinese Journal of Hepatobiliary Surgery 2013;(3):165-170
Objective To evaluate the impact of different treatment strategies on patients with hepatocellular carcinoma (HCC) of less than 10 cm but with portal vein tumor thrombus (PVTT),and to investigate the prognostic factors.Methods Between 2003 and 2008,338 HCC patients with PVTT from the Affiliated Tumor Hospital,Guangxi Medical University,were retrospectively studied.These patients were divided into four groups:the conservative treatment group (n =75),the transarterial chemoembolization (TACE) group (n=86),the surgical resection group (n =90) and the surgical resection with postoperative TACE group (n=87).Survival rates were analyzed by the Kaplan-Meier method and differences among groups were compared using the log-rank analysis.The Cox' s proportional hazards model was performed to explore the risk factors of survival.Results The mean survival periods of patients in the four groups were 3.8,7,8.2,15.1 months respectively.There were significant differences in survival rate among the 4 groups.The survival rates at 1-,2-,and 3-year in the surgical resection with postoperative TACE group were 49%,37% and 19%,which were significantly higher than the other 3 groups (P<0.05).The 1-,2-,and 3-year survival rates in the surgical resection group were 28%,20% and 15% compared with 17.5%,0% and 0% in the TACE group.The survival rates were significantly higher after surgical resection than TACE (P<0.05).The 1-,2-,and 3-year survival rates in the conservative treatment group were 0%.These were the lowest among the four groups (P<0.05).Univariate analysis indicated that portal vein occlusion by tumor thrombus was a significant predictor of poor prognosis.Multivariate analysis revealed that the strategy of treatment (TACE) and the number of TACE cycles were independent survival predictors for HCC patients with PVTT.Conclusions Surgical resection is the most effective therapeutic strategy for HCC patients with PVTT and with good liver functional reserve.Postoperative TACE is necessary in preventing recurrence and prolonging survival in patients who could tolerate chemoembolization.TACE should be recommended as an effective and safe treatment for unresectable HCC patients with PVTT.The treatment provided a significantly better survival than conservative treatment.

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