1.Value of accordion severity grading system in predicting short-term outcome after orthotopic liver transplantation for severe hepatitis
Qikun ZHANG ; Menglong WANG ; Haitao ZHANG ; Zhen ZHANG ; Tianchi YANG
Chinese Journal of Organ Transplantation 2016;37(12):736-741
Objective To explore the value of the Accordion severity grading system (ASGS) in predicting short-term outcomes after orthotopic liver transplantation for severe hepatitis by classifying post-surgery complications.Methods The clinical documents of 159 patients were retrospectively analyzed who underwent orthotopic liver transplantation for severe hepatitis between Aug.1,2004 to Sept.1,2014 at our center.Complications were categorized according to the ASGS:grade 1 (mild),grade 2 (moderate),grade 3-5 (severe),and grade 6 (death).Outcome measures included ventilator support time,the length of ICU stay,postoperative recovery time.Spearman rank correlation analysis was used to test the correlation between the different grades with these outcome measures.1-year survival trends of different grade complication groups were demonstrated by Kaplan-Meier method and compared by Log-rank test.Results In total,43 (27.0%) patients had a grade 2 complication;41 (25.8%) grade 3;31 (19.5%) grade 4;9 (5.7%) grade 5;and 35 (22.0%) grade 6.There was no grade 1 patient.There was a significant correlation between the complication grades and the ventilator support time,the length of ICU stay and postoperative inpatient time (P<0.01).With the increase of the complication grades,the outcome measures were even worse.Severe grade complication group had a longer ventilator support time,the length of ICU stay and postoperative inpatient time than the moderate grade complication group (P<0.01).There was a significant downward trend in 1-year survival with the increase of the complication grade (P<0.01).Conclusion The ASGS is helpful to assess risks and predict short-term outcomes after liver transplantation for severe hepatitis.Higher Accordion grades are correlated with even worse short-term outcomes.
2.Age impact in mouse model of secondary hepatic alveolar echinococcus
Haiyang XIA ; Jiefeng ZHAO ; Qikun WANG ; Li LI ; Jingxia TANG ; Shijie ZHANG ; Xinyu PENG ; Hongqiang YANG
Chinese Journal of Zoonoses 2014;(7):723-726,732
Age impact in mouse model of secondary hepatic alveolar echinococcus was investigated in this research . Twenty-nine 8-week-old ,twenty-five 18-week-old and twenty-five 28-week-old female mice were anesthetized with 20% ure-thane by intraperitoneal injection and then transhepatically injected by Echinococcus multilocularis (E .m) tissue suspension through skin incision and abdominal muscle to liver in all three groups to establish mouse model of secondary hepatic alveolar e-chinococcus .Results showed that the survival rates for the three groups of mice were 62 .1% ,84% and 68% ,respectively (P>0 .05) .The E .m infection rates in liver were 72 .2% ,71 .4% and 76 .5% ,respectively (P>0 .05) .The diameter of E .m cysts in liver were 0 .915 ± 0 .103 cm ,1 .247 ± 0 .112 cm and 1 .215 ± 0 .197 cm ,respectively (P>0 .05) .The mass of E .m cysts in liver were 0 .332 ± 0 .035 g ,0 .532 ± 0 .155 g and 0 .382 ± 0 .085 g ,respectively (P> 0 .05) .HE stain showed no difference in pathology .Results indicated that the establishment of secondary hepatic alveolar echinococcus model by using transhepatic injection through skin incision and abdominal muscle of 18-week-old mice was capable of simplifying operation and improving the survival rate of the mice .
3.Distribution of endogenous sulfur dioxide in severe acute pancreatitisrats
Qikun WANG ; Jianyun YUE ; Yan LU ; Luanluan ZHANG ; Xiaoyun GUO ; Chen CHAI ; Rong ZHOU
Chinese Journal of Emergency Medicine 2015;24(10):1111-1114
Objective The present study is to investigate the distribution of endogenous sulfur dioxide (SO2) in severe acute pancreatitis (SAP) rats.Methods Thirty-two SPF male Sprague-Dawley rats were randomized (random number) into sham operation group,SAP rat 3 h group (SAP 3 h),SAP rat 6 hgroup (SAP6h),SAP rat 12 hgroup (SAP 12 h),n=8 in each group.The SAPmodel rats were induced by retrograde cholangiopancreatic infusion of 5% sodium taurocholate.Rats were sacrified 3 h,6 h or 12 h after treatment.,then we collected pancrease,liver,lung,kidney and serum.The SO2 concentration in each tissue or serum was detected by enzyme-linked immune sorbentassay.Results The concentration of SO2 in tissues of pancreas (1.72 ± 0.14) μmol/g,liver (1.62 ± 0.11) μmol/g,lung (1.65 ± 0.11) μ.mol/g,kidney (1.12 ± 0.06) μmol/g or serum (16.80 ± 1.27) μmol/g in SAP 3 h rats was not significant compared with the sham operation group (P > 0.05 in each group).The SO2 content in the pancreas (1.89 ± 0.17) μmol/g,liver (1.92 ± 0.16) μmol/g,lung (1.91 ± 0.15) μmol/g,kidney (1.30 ± 0.10) μmol /g and serum (14.93 ± 1.00) μmol /g of SAP 6 h was significantly increased compared with sham operation group (P < 0.05 each group).The content SO2 in the pancreas (2.31 ± 0.23) μmol /g,liver (2.22 ± 0.15) μmol /g,lung (2.17 ± 0.07)μmol /g,kidney (1.55 ± 0.15) μmol /gand serum (18.88 ± 1.56) μmol /g of SAP rats reached the peak 12Hafter treatment and was significantly higher compared with the sham operation group (P < 0.05).Conclusions The increase of SO2 concentration in SAP might be,at least in our present opinion,involved into the pathogenesis of SAP rats.
4.Expression of TRPM7 protein in cholangiocarcinoma and its correlation with prognosis
Li LI ; Yuwen CAO ; Hexing WU ; Qikun WANG ; Xiao CHU ; Lin YANG ; Jingxia TANG ; Xinyu PENG ; Shijie ZHANG ; Hongqiang YANG
Chongqing Medicine 2015;(25):3523-3525,3528
Objective To evaluate the expression of transient receptor potential melastatin 7(TRPM7)in cholangiocarcinoma and its correlation with prognosis.Methods The expressions of TRPM7 were detected by SP immunohistochemical in 49 cases of cholangiocarcinoma,7 cases of benign bile duct lesions and 36 cases of adjacent histologically noncancerous bile duct tissues,and to analysis its relationship with the clinical pathological characteristics of cholangiocarcinoma.Results The positive expression rate of TRPM7 in cholangiocarcinoma was 77.6%(38/49),which was higher than that in benign bile duct lesions(0,0/7)and adjacent his-tologically noncancerous bile duct tissues(2.8%,1/36),the difference was statistically significant(P <0.05).The positive expres-sion of TRPM7 in cholangiocarcinoma was correlated with the TNM stage of tumor,lymph node metastasis and organ metastasis (P <0.05),but not related to patients′age,gender,site,differentiation and hepatitis(P >0.05).Kaplan-Meier analysis showed that increased expression of TRPM7 was associated with shorted overall survival (P <0.05).Cox regression analysis showed that the expression level of TRPM7 was significantly associated with prognosis and an independent risk factor for prognosis(P <0.05 ). Conclusion TRPM7 plays an important role in the tumorigenesis progression,invasion,and metastasis of cholangiocarcinoma,and is an important factor for prognosis in patients with cholangiocarcinoma.
5.The predictive value of different scoring models on short-term outcome in patients with hepatitis B-related acute-on-chronic liver failure undergoing liver transplantation
Chinese Journal of Hepatobiliary Surgery 2021;27(6):438-444
Objective:To compare the prognostic accuracy of 16 pre-transplant scoring models in predicting the post-transplant short-term outcome of patients with hepatitis B-related acute-on-chronic liver failure (HBACLF), and to explore an efficient predictive model.Methods:A retrospective analysis of the clinical data of HBACLF patients who underwent liver transplantation at the Liver Transplant Center of Beijing Youan Hospital from August 2004 to September 2014. Score of 16 models (CTP, UNOS-MELD, Updated-MELD, Integrated-MELD, MELD-Na, MLED Na, CLIF-SOFA, CLIF-OFs, CLIF-C ACLFs, CLIF-C ADs, Refit MELD, Refit MELD Na, MELD-AS, Zheng's Risk, UKELD, MESO) was based on time-dependent operation characteristic curve, and the area under the curve (AUC) was calculated to evaluate the prediction accuracy of 3-month survival after transplantation. Selection of univariate factors associated with postoperative short-term mortality was performed, and then 16 scoring models one by one with statistically significant mortality-related factors were entered into LASSO regression (Least Absolute Shrinkage and Selection Operator regression) to confirm the independent variables. Finally, a predictive model was constructed by Cox regression.Results:A total of 135 patients were included in this study, including 106 males and 29 females, aged (45.0±10.5) years old. Among the 16 scoring models, the AUC of MELD-Na and CLIF-SOFA were more than 0.7 in early survival prediction after liver transplant. The MELD-Na was confirmed as an independent predictive variable in the final model with univariate and LASSO regression multivariate selection analysis ( HR=1.0481, 95% CI: 1.0136-1.0838, P<0.05). The model was constructed by MELD-Na and combined with other clinical parameters (female, systemic infection, placement of T tube during operation) could better predict the early survival after liver transplant. The overall C-index of the final model was 0.886, and the C-index at 3-month after liver transplant was 0.844 through internal validation (Bootstrap). Conclusion:Compared with other scoring models, MELD-Na and CLIF-SOFA were better for early survival prediction after liver transplantation for patients with HBACLF. The constructed predictive model based on MELD-Na was superior than single MELD-Na or CLIF-SOFA in prognostic assessment and case selection.
6.The impact of splenectomy and devascularization on liver function and liver fibrosis in patients with non-cirrhotic portal hypertension
Hongwei ZHANG ; Menglong WANG ; Zhen ZHANG ; Haitao ZHANG ; Qikun ZHANG
Chinese Journal of Hepatobiliary Surgery 2019;25(7):501-504
Objective To study the impact of splenectomy and devascularization on liver function and liver fibrosis in patients with non-cirrhotic portal hypertension (NCPH). Methods The clinical data of patients with NCPH who were treated in Beijing You'an Hospital of Capital Medical University from April 2008 to December 2017 were retrospectively analyzed. The patients were divided into the observation group (n=16 ) and the control group ( n =30 ) according to their treatment methods. The observation group underwent splenectomy combined with devascularization, while the control group received conservative treatment. The changes in liver function, ascites, varicose vein rupture and bleeding before and after treat-ment, and the changes in liver blood flow before and after treatment in the observation group were compared. Results The before and after treatment of the 2 groups in ALT, AST, total bilirubin, albumin showed no statistically significant difference (P>0. 05). Six months after treatment, the rates of ascites and bleeding were significantly higher than the observation group, (P<0. 05). Ten patients who had a history of preoper-ative variceal hemorrhage in the observation group did not bleed within 6 months after treatment. Further-more, in the observation group after treatment when compared with the control group, the PC-Ⅲ [(32. 3 ± 12. 1) g/L vs. (56. 7 ± 15. 3)g/L],Ⅵ-C [(46. 6 ± 35. 0) g/L vs. (121. 3 ± 30. 4)g/L], LN [(32. 5 ± 10. 5) g/L vs. (65. 8 ± 11. 1) g/L] were significantly lower than the control group ( P <0. 05). The preoperative portal venous blood flow in the observation group was significantly higher than that after surgery [(1 056. 8 ± 679. 8) ml/min vs. (481. 0 ± 227. 6) ml/min, P<0. 05]. Conclusion Splenectomy and devascularization effectively stopped variceal bleeding and delayed liver fibrosis in NCPH patients without affecting the liver function.
7.The value of MELD-Na score in predicting complication severity grades after orthotopic liver transplantation for severe hepatitis
Qikun ZHANG ; Menglong WANG ; Shichun LU ; Jushan WU ; Qingliang GUO ; Dongdong LIN ; Zhen ZHANG ; Haitao ZHANG ; Jinning LIU ; Xin WANG ; Lu WANG
Chinese Journal of Hepatobiliary Surgery 2017;23(12):793-798
Objective To study the value of preoperative MELD-Na score (Model for End-Stage Liver Disease-Sodium) in predicting complication severity grades after liver transplantation (LT) for severe hepatitis.Methods Patients who underwent LT for severe hepatitis between August 1,2004,and September 1,2014 were retrospectively studied.The Accordion severity grading system was used to classify the complication severity grades after LT.The grades were classified as grade 1 (mild),grade 2 (moderate),grade 3-5 (severe),and grade 6 (death).The area under the curve (AUC) was calculated by plotting the receiver operating characteristic curve (ROC) to evaluate the predictive accuracy of the MELD-Na score for the severe and mortality grades after LT.The correlation between the MELD-Na score with the complication severity grade after LT was studied by the Spearman correlation and by multivariate analysis.Results The incidences of postoperative complications for the 159 patients in this study were:grade 2 in 43 patients (27.0%,MELD-Na score 27.3 ±7.4),grade 3 in 41 patients (25.8%,MELD-Na score 32.7 ± 12.4),grade 4 in 31 patients (19.5%,MELD-Na score 34.3 ± 12.1),grade 5 in 9 patients (5.7%,MELD-Na score 30.7 ± 12.3),grade 6 in 35 patients (22%,MELD-Na score 37.1 ± 10.4).There was no grade 1 patient.The AUC of the MELD-Na score for the severe and death groups were 0.631 (P < 0.05;95 % CI,0.533 ~ 0.728) and 0.670 (P < 0.05;95 % CI,0.574 ~ 0.766) respectively.The MELD-Na score was significantly correlated with the Accordion severity grade (rho 0.297,P < 0.01) on Spearman correlation analysis.Multivariate analysis showed that a MELD-Na score ≥25 was a risk factor of postoperative severe grade complication (P < 0.05,OR =4.35),a MELD-Na score ≥35 was a risk factor of postoperative mortality (P <0.01,HR =4.72).Conclusion The MELD-Na score was significantly correlated with the Accordion severity grade,which efficaciously predicted the complication severity grades after liver transplantation.
8.Recent progress of hypoxia-modulated multifunctional nanomedicines to enhance photodynamic therapy: opportunities, challenges, and future development.
Yixin SUN ; Dongyang ZHAO ; Gang WANG ; Yang WANG ; Linlin CAO ; Jin SUN ; Qikun JIANG ; Zhonggui HE
Acta Pharmaceutica Sinica B 2020;10(8):1382-1396
Hypoxia, a salient feature of most solid tumors, confers invasiveness and resistance to the tumor cells. Oxygen-consumption photodynamic therapy (PDT) suffers from the undesirable impediment of local hypoxia in tumors. Moreover, PDT could further worsen hypoxia. Therefore, developing effective strategies for manipulating hypoxia and improving the effectiveness of PDT has been a focus on antitumor treatment. In this review, the mechanism and relationship of tumor hypoxia and PDT are discussed. Moreover, we highlight recent trends in the field of nanomedicines to modulate hypoxia for enhancing PDT, such as oxygen supply systems, down-regulation of oxygen consumption and hypoxia utilization. Finally, the opportunities and challenges are put forward to facilitate the development and clinical transformation of PDT.
9.Structurally defined tandem-responsive nanoassemblies composed of dipeptide-based photosensitive derivatives and hypoxia-activated camptothecin prodrugs against primary and metastatic breast tumors.
Mengchi SUN ; Hailun JIANG ; Tian LIU ; Xiao TAN ; Qikun JIANG ; Bingjun SUN ; Yulong ZHENG ; Gang WANG ; Yang WANG ; Maosheng CHENG ; Zhonggui HE ; Jin SUN
Acta Pharmaceutica Sinica B 2022;12(2):952-966
Substantial progress in the use of chemo-photodynamic nano-drug delivery systems (nano-DDS) for the treatment of the malignant breast cancer has been achieved. The inability to customize precise nanostructures, however, has limited the therapeutic efficacy of the prepared nano-DDS to date. Here, we report a structurally defined tandem-responsive chemo-photosensitive co-nanoassembly to eliminate primary breast tumor and prevent lung metastasis. This both-in-one co-nanoassembly is prepared by assembling a biocompatible photosensitive derivative (pheophorbide-diphenylalanine peptide, PPA-DA) with a hypoxia-activated camptothecin (CPT) prodrug [(4-nitrophenyl) formate camptothecin, N-CPT]. According to computational simulations, the co-assembly nanostructure is not the classical core-shell type, but consists of many small microphase regions. Upon exposure to a 660 nm laser, PPA-DA induce high levels of ROS production to effectively achieve the apoptosis of normoxic cancer cells. Subsequently, the hypoxia-activated N-CPT and CPT spatially penetrate deep into the hypoxic region of the tumor and suppress hypoxia-induced tumor metastasis. Benefiting from the rational design of the chemo-photodynamic both-in-one nano-DDS, these nanomedicines exhibit a promising potential in the inhibition of difficult-to-treat breast tumor metastasis in patients with breast cancer.