1.CA Ⅸ-targeted Ag2S quantum dots bioprobe for NIR-Ⅱ imaging-guided hypoxia tumor chemo-photothermal therapy
Cui XINYUE ; Hu ZHUANG ; Li RUIHAN ; Jiang PENG ; Wei YONGCHANG ; Chen ZILIN
Journal of Pharmaceutical Analysis 2024;14(6):878-888
Hypoxia is the common characteristic of almost all solid tumors,which prevents therapeutic drugs from reaching the tumors.Therefore,the development of new targeted agents for the accurate diagnosis of hypoxia tumors is widely concerned.As carbonic anhydrase Ⅸ(CA Ⅸ)is abundantly distributed on the hypoxia tumor cells,it is considered as a potential tumor biomarker.4-(2-Aminoethyl)benzenesulfo-namide(ABS)as a CA Ⅸ inhibitor has inherent inhibitory activity and good targeting effect.In this study,Ag2S quantum dots(QDs)were used as the carrier to prepare a novel diagnostic and therapeutic bio-probe(Ag2S@polyethylene glycol(PEG)-ABS)through ligand exchange and amide condensation reaction.Ag2S@PEG-ABS can selectively target tumors by surface-modified ABS and achieve accurate tumor im-aging by the near infrared-Ⅱ(NIR-Ⅱ)fluorescence characteristics of Ag2S QDs.PEG modification of Ag2S QDs greatly improves its water solubility and stability,and therefore achieves high photothermal sta-bility and high photothermal conversion efficiency(PCE)of 45.17%.Under laser irradiation,Ag2S@PEG-ABS has powerful photothermal and inherent antitumor combinations on colon cancer cells(CT-26)in vitro.It also has been proved that Ag2S@PEG-ABS can realize the effective treatment of hypoxia tumors in vivo and show good biocompatibility.Therefore,it is a new efficient integrated platform for the diagnosis and treatment of hypoxia tumors.
2.Clinical application of robotic-assistant living donor left lateral segmentectomy
Yamin ZHANG ; Wei GAO ; Zilin CUI ; Chong DONG ; Rui FENG ; Chao SUN ; Yi BAI ; Zhongyang SHEN
Chinese Journal of Organ Transplantation 2023;44(6):339-345
Objective:To explore the feasibility and safety of robotic-assisted living donor left lateral segmentectomy (LDLLS) in a large pediatric liver transplant program.Methods:Retrospective analysis was performed for clinical data of 45 LDLLS donors and recipients from June 2021 to September 2022.Traditional open donor liver resection (n=30) and robotic-assisted segmentectomy (n=15) were performed.Two groups were compared with regards to operative duration, intraoperative hemorrhage, postoperative healing and postoperative complications.SPSS 21.0 was utilized for statistical analysis.Independent sample T, paired sample T, Wilcoxon rank sum and Chi-square tests were performed for examining the inter-group differences.Results:Operative duration of robot-assisted surgery group was substantially longer than that of traditional open surgery group ( P<0.001). Intraoperative blood loss was less in robot-assisted surgery group was less than that in traditional open surgery group[(106.0±39.8) vs.(251.0±144.8) ml, P=0.001]. Postoperative hospital stay of robot-assisted surgery group was shorter than that of traditional open surgery group[6.0(6.0, 6.0) vs.7.0(6.0, 9.0), P<0.05]. Two cases of postoperative biliary leakage were observed in donor of traditional open surgery group.Among 2 cases of abdominal infection, one was due to biliary leakage from liver section and secondary surgery was then performed.One case of incisional infection and another case of thrombosis occurred in donor of traditional open surgery group.In robot-assisted surgery group, only one donor had amylase elevation.In traditional open surgery group, there were one case of local thrombosis in middle hepatic vein and one case of bile duct stricture.No long-term complications occurred in robot-assisted surgery group during a follow-up period of over 6 months.Finally recipient data analysis indicated that no significant inter-group differences existed in operative duration, intraoperative blood loss, postoperative hospital stay or postoperative abdominal infection ( P=0.634, P=0.180, P=0.86 and P=0.153). Conclusions:Robotic-assisted LDLLS proves to be be a safe and reliable option for living donor segmentectomy.It is superior to conventional LDLLS in terms of shorter hospital stay, less intraoperative blood loss and fewer postoperative complications.
3.Research progress in the role of HMGB1-RAGE signaling axis in hepatic ischemia-reperfusion injury
Li ZHAO ; Zilin CUI ; Yamin ZHANG ; Jie LIU
International Journal of Biomedical Engineering 2022;45(2):166-170,185
Hepatic ischemia-reperfusion injury(HIRI) is a kind of liver injury caused by reperfusion after ischemic injury, which is clinically manifested by a series of deterioration phenomena such as liver function impairment, jaundice and even multi-organ failure after restoration of blood supply to the liver. HIRI seriously affects the patient's regression and prognosis. The essence of HIRI is a sterile inflammatory response. High mobility histone 1 (HMGB1) is an important intermediate mediator of HIRI and is a multiple cell type effector involved in HIRI. The receptor for glycosylated end products(RAGE) signaling axis of HMGB1 plays a key role in HIRI, but its mechanism is unclear. In this paper, the recent studies related to the pro-inflammatory mechanism of HMGB1-RAGE signaling axis in HIRI were summarized, and the relationship between HMGB1-RAGE signaling pathway and HIRI was discussed. The research progress of preventing and treating HIRI with surgical operation, ischemic preconditioning, drug and gene therapy using HMGB1-RAGE signaling axis as the target was reviewed.
4.Functional remnant liver volume to spleen volume ratio is a useful predictive factor for posthepatectomy liver dysfunction
Jiancan HOU ; Yamin ZHANG ; Yang LI ; Zilin CUI ; Xiaolong LIU ; Lianjiang WANG ; Rui SHI ; Zirong LIU ; Hong ZHENG ; Zhongyang SHEN
Chinese Journal of Hepatobiliary Surgery 2018;24(10):671-675
Objective Toidentify factors contributing to posthepatectomy liver dysfunction (PHLD),focusing on the Functional remnant liver volume to spleen volume ratio (FreLSVR).Methods The clinical data of 74 patients undergoing precise liver resection from January 2016 to October 2017 were retrospectively analyzed.IQQA liver system was used to reconstruct the liver and spleen 3D image by using patients' preoperative abdominal CT image data.Tumor volume,3D estimated functional residual liver volume,spleen volume and FreLSVR were measured and calculated.Preoperative and postoperative liver function test,blood coagulation function test,operation time,intraoperative blood loss,and the volume of daily postoperative abdominal drainage were recorded.Correlations between multiple parameters and PHLD were analyzed.Results PHLD occurred in 16 (21.6%).Single factor analysis revealed that the standardized residual liver volume ratio (P<0.05),FreLSVR (P<0.05) and preoperative AST value (P<0.05) were correlated with postoperative hepatic insufficiency.Multivariate regression analysis showed that FreLSVR (OR=0.535,95%CI=0.305~0.936,P<0.05) was the only independent factor of PHLD.In the ROC curve analysis for FreLSVR,a cut-off value of 2.56 (AUC=0.824,Sensitivity 81.1%,specificity 71.7%.) was the appropriate value for predicting the risk of PHLD according to Youden index.Then the patients were regrouped according to this cut-off value.Compared with the FreLSVR>2.56 group (53 cases),the highest postoperative INR value (1.46± 0.19 to 1.29± 0.29,t=-2.405,P<0.05) was higher that of FreLSVR≤2.56 group,and the amount of average daily abdominal drainage in one and two weeks after operation was higher,(188.0(79.2 ~ 375.1)ml to 96.0(46.5 ~ 179.3)ml,P<0.05) and (207.2(125.6 ~ 827.1)ml to71.8(14.0 ~ 179.8) ml,P<0.05),respectively.Conclusion FreLSVR has significant correlation with postoperative hepatic dysfunction,and provides guidance for the safety of liver resection in the future.
5.The role of interleukin-22 in liver regeneration after partial hepatectomy with liver fibrosis in mice
Di ZHANG ; Yamin ZHANG ; Zilin CUI ; Long YANG ; Yang LI
Chinese Journal of Hepatobiliary Surgery 2017;23(1):48-53
Objective To study the promoting effects and mechanisms of interleukin-22 on liver regeneration in GCl4-induced liver fibrosis mice after partial hepatectomy.Methods One hundred and fortyfour C57/BL6 mice were randomly divided into four groups:PHX group,CCl4 group,CCl4 + PHX group,and CCl4 + IL22 + PHX group.The blood samples were taken to measure serum ALT and AST levels.ALT /AST was calculated to observe the liver injury at 3 h,6 h,12 h,24 h,48 h and 72 h after hepatectomy.The liver tissue specimens were collected at each time point after hepatectomy.We measured the hepatic lobe to calculate the liver weight ratio and conducted pathological examinations to observe the degree of fibrosis and pathological changes at each time point.The positive expression of proliferating cell nuclear antigen (PCNA) in liver tissue was tested by immunohistochemistry.The level of CyclinD1 and STAT3 (Signal transducer and activator of transcription 3) signaling pathway was detected by Western blot.Results (1) Compared with CCl4 + PHX group,the ALT/AST ratio of CCl4 + IL22 + PHX group was significantly higher at 24 h,48 h and 72 h,and the level of ALB of CCl4 + IL22 + PHX group was obviously increased at 48 h and 72 h (P < 0.05).(2) The liver regeneration was significantly increased in CCl4 + IL22 + PHX group.Compared with CCl4 + PHX group (2.08 ± 0.16,2.77 ± 0.07,2.97 ± 0.14),the liver weight ratio of CCl4 + IL22 + PHX group(2.34 ± 0.07,3.23 ± 0.09,3.55 ± 0.09) dramatically increased at 24 h,48 h and 72 h.Moreover,the pathological sections displayed that the disease was alleviated (P < 0.05).(3) Immunohistochemical assay and western blot revealed that compared with other three groups,the level of PCNA,STAT3 and Cyclin D1 was significantly lower in the CCl4 + PHX group.However,the level of PCNA,STAT3 and Cyclin D1 apparently increased in CCl4 + IL22 + PHX group at 24 h,48 h and 72 h (P < 0.05).Conclusion Interleukin-22 may significantly promote liver regeneration and reduce liver pathological injury in liver fibrosis mice induced by administration of CCl4 after hepatectomy,which plays a positive role in the recovery of liver function.
6.Liver transplantation for patients with hepatopulmonary syndrome: long-term follow-up and prognosis analysis
Jindan HE ; Shipeng LI ; Zhen WANG ; Yao YU ; Haiming ZHANG ; Zilin CUI ; Wenli YU ; Zhijun ZHU ; Hongyin DU
Chinese Journal of Hepatobiliary Surgery 2017;23(3):145-148
Objeetive To analyze the clinical efficacy of liver transplantation (OLT) for patients with hepatopulmonary syndrome (HPS).Methods From 2008 to 2013,420 adult patients underwent liver transplantation in our hospital.There were 91 patients with,and 329 patients without,HPS.The 5-year survival and mortality rates after OLT for the two groups were retrospectively analyzed.Results There were no significant differences between patients without and with HPS in age,primary disease,Child-Pugh score,MELD score,cold ischemia time and warm ischemia time.However,the differences on serum albumin [(29.6 ± 1.2) g/L vs.(26.4 ± 1.6) g/L] and blood oxygen pressure [(61.0 ±9.0) mmHg (1 mmHg =0.133 kPa) vs.(87.0 ± 6.0) mmHg] were significantly different (P < 0.05).The 1-year cure rate was 65.9% (60/91) in 91 patients with HPS after liver transplantation.The 1,3,5-year cumulative survival rates for patients without HPS were 97.3%,90.9% and 80.3%,respectively,and the main causes of death were primary graft dysfunction,recurrent cardiovascular events and primary disease recurrence or tumors.The 1,3,5-year cumulative survival rates for patients with HPS were 65.9%,59.3% and 56.0%,and the main causes of death were multiple-organ failure,pulmonary infection and cerebrovascular events.Kaplan-Meier survival curve analysis showed that the survival of patients with HPS was significantly lower than that of patients without HPS (P < 0.05).Conclusions Liver transplantation is the most effective treatment for patients with HPS,but the short-term mortality rate is relatively high.We still need to learn more about HPS to improve the survival rate of patients with HPS after liver transplantation.
7.Comparison of 70%hepatectomy model established by two different methods in liver fibrosis mice
Di ZHANG ; Yamin ZHANG ; Zilin CUI ; Long YANG ; Yang LI
Tianjin Medical Journal 2017;45(1):17-20
Objective To explore a reliable method of 70% hepatectomy model in liver fibrosis mice. Methods Sixty-six C57BL6 mice were randomly devided into control group (n=6), the traditional group (n=30, ligation and removal liver lobe) and improved group (n=30, removal of liver lobe after blocking blood flow). Those 60 mice were induced liver fibrosis firstly, then randomly divided into six mice in each group, and were sacrificed at preoperative, 12, 24, 48 and 72 hours after liver resection. Liver tissues and blood samples were collected. The survival rate and incidence of complications were recorded and compared between two groups. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured to observe the liver injury after 70%hepatectomy. The ratio of liver weight to body weight and the expression of proliferating cell nuclear antigen (PCNA) were also measured to observe the difference of liver regeneration between the two groups. Results (1) Compared to the pathological control group, liver fibrosis model was established successfully in both traditional group and improved group, which can be used in 70%hepatectomy. So the follow-up experiment can be undertook timely. (2) Compared to traditional group, the survival rate was improved significantly in improved group (96.67%vs. 73.33%), and the incidence of complications was significantly lower (P<0.05). (3) The ALT and AST levels were higher 12 h and 24 h after operation in traditional group than those of improved group (P<0.05), while ALT and AST levels were increased first 12 h after operation and then decreased in both groups (P<0.05). (4) The liver/body weight ratio showed a decreasing trend 12 h after hepatectomy in two groups. The expression of PCNA increased at the beginning of postoperative, and reached its peak at 48 h (P<0.05). However, there was no significant difference at each time point between the two groups. Conclusion By blocking blood flow to establish 70% hepatectomy model in liver fibrosis mice, we can significantly improve the success rate of the model, and reduce the incidence of complications.
8.Clinical treatment and prognosis of de novo liver cancer following renal transplantation
Yamin ZHANG ; Zirong LIU ; Zilin CUI ; Yang LI ; Lianjiang WANG ; Jian WANG ; Zhongyang SHEN
Chinese Journal of Hepatobiliary Surgery 2017;23(7):441-443
Objective To study the clinical treatment and prognosis of de novo liver cancer following renal transplantation.Methods The clinical data of 15 patients who developed de novo liver cancer after renal transplantation carried out prior to treatment of liver cancer at the First Center Hospital of Tianjin between June 2006 and June 2016 were retrospectively studied.These patients were diagnosed to have liver cancer ranging from 23 to 98 months after renal transplantations,with an average of (42.5 ± 29.7) months.Two patients were diagnosed within 2 years,7 within 5 years,and 6 over 5 years after renal transplantation.Results Three patients underwent transcatheter arterial chemoembolization (TACE) and 12 patients underwent surgical resection which included right/left hemihepatectomy (n =5),hepatic segment resection (n =4),and tumor enucleation (n =3).Postoperative histopathology confirmed hepatocellular carcinoma in 8 patients,cholangiocarcinoma in 1 patient,and mixed liver cancer in 3 patients.Among the 12 patients who initially underwent'curative'surgery,3 patients died from recurrent cancer 8,16,25 months after surgery,respectively.The remaining 9 patients were still alive with a follow-up which ranged from 0.6 to 65-month.The 3 patients who underwent TACE were alive for 4,7 and 13 months,respectively.Conclusions De novo liver cancer were usually asymptomatic and had a rapid onset.The optimal clinical management which includes early diagnosis,appropriate therapy with immunosuppression and renal function preservation can result in good long-term survival.
9.IRF-1'role in liver ischemia reperfusion injury in mice
Zilin CUI ; Zirong LIU ; Haiming ZHANG ; Shipeng LI ; Yamin ZHANG
Chinese Journal of Hepatobiliary Surgery 2017;23(4):255-258
Objective To investigate the role of interferon regulatory factor-1 (IRF-1) in liver ischemia/reperfusion (IR) injury and its underlying mechanism,and identify effective managements in alleviating liver IR injury.Methods Three groups of mice models with liver IR injury were well established,including control group (S),warm liver IR injury group (IR) and recombinant IRF-1 group (IRF-1).The levels of mRNA and protein,liver function and pathological changes of liver tissue were detected in group S and group IR.Additionally,the marker of IRF-1,p-Stat1,p-P38,PARP1 and Caspase-3 were measured and PCNA expression was determined in group IR and group IRF-1 mice with 6-hour liver IR injury.Results IRF-1 mRNA and protein and the levels expression of proteins were significantly elevated with peak occurred after 6-hour IR injury,which was statistic difference compare to the group S (t2h =-3.512,t6h =-4.247,t12h =-4.088,t24h =-3.851;P < 0.05).Serum ALT and AST of mice detected in group IR were higher than group S at all endpoints (tALT =4.931,4.592,4.277,4.809;tAST =4.980,4.617,4.336,4.915;P < 0.05).Furthermore,pathological damage change was more distinct compared with group S.The elevated levels of IRF-1,p-Statl,p-P38,PARP1 and Caspase-3 and decreased PCNA expression were determined in mice models with recombinant IRF-1 intervention.Conclusion IRF-1 expression could be closely correlated with liver IR injury,and its underlying mechanism may be attributed to activation of JNK MAPK protein and inhibition of PCNA expression.
10.Impact of different ways of perfusion on the survival rate of small-for-size liver transplantation in rats
Chao YANG ; Yamin ZHANG ; Zilin CUI ; Zirong LIU ; Yuan SHI ; Zhongyang SHEN
Tianjin Medical Journal 2016;44(2):178-181
Objective To investigate the effects of different hepatic perfusion procedures for small-for-size liver transplantation in rats. Methods A total of 156 rats were randomly divided into two groups: portal vein perfusion group (groupⅠ, n=78) and abdominal aorta perfusion group (groupⅡ, n=78). After harvesting graft, the left lobe of the liver and the middle lobe were resected and the remaining approximately 30%volumes of the liver were transplanted in groupⅠand groupⅡ. The body weights of donor and acceptor, the weight of graft, the time of operating in donor, the cold ischemia time, anhepatic phase, the blocking time of inferior hepatic vena cava and the time of operating in receptor were recorded in two groups. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), pathological HE staining and 7-day survival rate in 6 h, 1 d, 3 d and 7 d after operation were compared between two groups. Results The serum levels of ALT and AST were decreased gradually in two groups, but the levels decreased slowly in groupⅠ. The serum levels of ALT and AST were significantly higher in groupⅠthan those of groupⅡ(P<0.05). HE staining showed greater damage of mi-crostructure of liver tissue at early stage in group Ⅰthan that in groupⅡ. The 7-day survival rate was lower in group Ⅰthan that of groupⅡ(χ2=4.050,P=0.044). Conclusion There is a higher survival rate and mild liver damage in small-for-size liver transplantation in rats using perfusion by abdominal aorta.

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