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Abnormal FGFR signaling has been found in a variety of cancers. The abnormal FGFR signaling is involved in several processes of tumorigenesis which include cell survival, proliferation, inflammation, migration, angiogenesis, epithelial-mesenchymal transformation and drug resistance. Therefore, FGFR is a very promising target for the treatment of tumors. More and more FGFR inhibitors have been developed for preclinical and clinical trials, and some FGFR inhibitors have been used in clinical applications. However, the problems such as acquired resistance and systemic toxicity have hindered the application of FGFR inhibitors. This paper reviews the clinical application of common FGFR inhibitors and summarizes the problems and solutions in their application.
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Endoscopic retrograde cholangiopancreatography (ERCP) is an irreplaceable measure with minimally invasive diagnosis and treatment of endoscopy for biliary and pancreatic diseases, but the related complications associated with ERCP are the highest among the endoscopic procedures. Post-ERCP pancreatitis (PEP) is one of the most common complications with life-threatening in severe cases. Early active prevention can effectively reduce the incidence of post-ERCP pancreatitis. At present, measures including preoperative rectal non-steroidal anti-inflammatory drugs and prophylactic pancreatic stent placement, have definite effective strategy in clinic. Aggressive hydration with lactated Ringer's solution is also a safe and effective way to prevent PEP.
Subject(s)
Humans , Anti-Inflammatory Agents, Non-Steroidal , Cholangiopancreatography, Endoscopic Retrograde , Incidence , Pancreatitis , Risk Factors , StentsABSTRACT
The anoikis resistance confers the ability of cancer cells to survive and metastasize in the blood circulation without adhesion,but its effect and mechanism in intrahepatic and distant metastasis of hepatocellular carcinoma has not been fully elucidated.Recent studies have shown that certain factors or drugs may inhibit anoikis of hepatoma cells through some signaling pathways.These signaling pathways are not completely separated,they are interconnected to promote metastasis of hepatocellular carcinoma.Liver is the metabolic center of many substances,and many related factors can promote metastasis of hepatocellular carcinoma through inhibiting anoikis.In this review,we summarized the signaling pathways of anoikis resistance of hepatocellular carcinoma.
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Shortage of donors is a major obstacle for liver transplantation.Lee innovated dual graft living donor liver transplantation in 2001,obtained graft from two donors,and it was conducted in various parts of the world.At present,South Korea has the biggest numbers in operation,China,Japan,and Germany.Turkey,Romania,and other countries are relatively less;current clinical liver donor liver transplantation is mainly based on single graft living donor liver transplantation,and in some complicated cases,single graft liver transplantation cannot be completed due to various factors,at this situation dual grafts living donor liver transplantation can complete the treatment.Although dual donor liver transplantation can only be carried out in a few areas due to complex surgical procedures,it can enrich the treatment of liver transplantation and promotes the development of liver transplantation.
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Pyroptosis is a form of new programmed cell death which is dependent on Caspase-1 in recent years.When it' s stimulated by various dangerous signals from hepatic ischemia-reperfusion injury,the intracellular pattern recognition receptors are assembled into inflammasomes and Caspase-1 which was transformed into active form.Activated Caspase-1 promotes the maturation and secretion of pro-inflammatory cytokines IL-1β and IL-18,initiates the innate immunity rapidly and then induces severe inflammatory reaction.In addition,Caspase-1 can also cleave Gasdermin D and release its N-terminal domain triggering pyroptosis.Many studies showed that pyroptosis play a crucial role in hepatic ischemia-reperfusion injury.In this review,we discussed the activation mechanism and research progress of pyroptosis in hepatic ischemia-reperfusion injury.
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Cholangiocarcinoma is a malignant tumor originating from bile duct epithelial cells, among which hilar cholangiocarcinoma is the most common, accounting for about 58％-70％ of cholangiocarcinoma. Due to its atypical clinical features, special anatomical site, low radical resection rate, high recurrence rate and poor prognosis, the 5-year survival rate of hilar cholangiocarcinoma was only 14.7％-33.8％. Hence, the most effective method of hilar cholangiocarcinoma lies in early diagnosis and radical resection. Good perioperative management can improve the rate of radical resection of hilar cholangiocarcinoma and contribute a lot to prognosis of the patients. The perioperative management of hilar cholangiocarcinoma is described as follows.
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Primary liver cancer is one of the most malignant tumor in the worldwide.5 years recurrence rate of patients in the early phase is exceeding 70％.Recurrence of HCC is one of the vital factors leading to adverse outcomes.Researchers found that characteristics of tumors,such as tumor size,differentiation and vascular invasion;operation aspect,such as surgical margin width,surgical approach,intraoperative bleeding and transfusion;patient-self and liver transplantation related factors,such as liver disease,donor's age,hepatitis B virus infection of recipient can affect the postoperative recurrence of hepatocellular carcinoma.We summarized the influence factors of postoperative recurrence of HCC via literature review.
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Primary sclerosing cholangitis (PSC) is a common autoimmune liver disease,and the diversity of its treatment methods has been hotly discussed by scholars in various countries.As the best treatment,end-stage liver transplantation (LT),due to the related diseases,such as postoperative complications greatly limits its wide application in clinical practice.Early assessment and intervention can reduce the risk of concomitant disease and reduce the occurrence of postoperative complications.In this paper,the status of LT indications,timing and related disease management,postoperative complications and other aspects of PSC patients were reviewed.
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Objective To detect the plasma concentration of tacrolimus and the survival time of rats after small-volume liver transplantation,and to investigate the criteria for immunological rejection after small-volume liver transplantation.Methods Lewis rats and Brown Norway rats were used to establish a small volume and normal liver volume transplantation model,which were divided into 7 groups:whole liver transplantation group (WI),small volume allogeneic liver transplantation group (SI),and whole liver allograft group (WA),small volume allogeneic liver transplantation group (SA),whole liver allograft immunotherapy group (WAT),small volume allogeneic liver transplantation immunotherapy group (SAT),small volume allogeneic liver transplantation immunotherapy modulation group (SATa).Morphological and functional changes of liver tissue were studied postoperatively,AST and tacrolimus plasma concentrations were detected,and survival was recorded.Results Compared with the WA group,the inflammatory cells infiltrated in the portal area of the SA group,the inflammatory changes of the sinusoidal endothelial cells,and the proportion of TCRpositive lymphocytes increased.Four days after transplantation,peripheral blood tests showed that CD4+CD25+ double positive lymphocytes were significantly lower in the allograft group than in the allograft group,and the positive expression rate in the SA group (0.6％) was significantly lower than that in the WA group (1.8％).The differences were statistically significant (P＜0.05).In the SAT group,the blood concentration of tacrolimus was significantly higher than that in the WAT group at each time point (P＜0.05).The blood concentration of tacrolimus in the SATa group was relatively stable,and the plasma concentration of the SATa group was stable.And AST was significantly lower than the SAT group,the differences were statistically significant (P＜0.05).Compared with WAT group,the proliferation and apoptosis rate of hepatocytes in SAT group and SATa group were significantly increased.The proliferation of hepatocytes in SATa group was significantly higher than that in SAT group (P＜0.05).Survival analysis showed that the cumulative survival rate of the WA group was 85.7％,which was significantly higher than that of the SAT group (28.6％).The difference was statistically significant (P＜0.05).The cumulative survival rate of the SATa group was 51.7％.The survival time of WAt group was (57.4±25.0) days,SAT group was (28.0±29.10) days,SATa group was (39.7± 29.0) days,which were longer than untreated groups.The ratio of proliferation to apoptosis (PRA) increased with increasing time of tacrolimus.Regardless of blood concentration,tacrolimus plasma concentration was positively correlated with AST (R =0.758,P＜0.05),indicating RPA was inversely correlated with AST (R=-0.962,P＜0.05).Conclusion The use of tacrolimus significantly prolonged the survival time of small-volume allogeneic liver transplantation rats.Adjusting the amount of tacrolimus under the guidance of tacrolimus plasma concentration and AST serum value equation TD =-0.494TC-0.0035AST+ 260.487 to make the blood concentration relatively stable,it can further extend the allogeneic liver transplantation rat time to live.
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Objective To investigate effective approach to decrease portal venous hypertension and high perfusion of portal vein caused by small-for-size (SFS) liver graft transplantation with the aim of improving hepatocellular microcirculation.Methods Rat models with SFS liver graft (n =62) were well estab lished and divided into SFS group and trans-portal intrabepatic portosystemic shunt (TPIPSS) group.Hemodynamic parameters,histopathologically morphologic changes,postoperative complications,accumulated survival rate were recorded and analyzed.Venous filling time after liver reperfusion,hemodynamic parameters were evaluated using t test and Kruskal-Wallis test.Kaplan-Meier method was performed for survival analysis.Results Venous filling time after liver reperfusion was remarkably prolonged with the application of multihole cone-shaped tubes.Compared with SFS group,the filling time was 4-second longer in TPIPSS.At each endpoints of reperfusion within 90 mins,the portal vein pressures were lowered in the TPIPSS group than those of SFS group.Liver grafts were present with more regular structures in TPIPSS group,with no sign of hepatic sinusoid congestion or irregular clearance extension.In the aspect of postoperative complications,all the rat receivers showed ascites in the SFS group.Nevertheless,there was no ascites observed in TPIPSS rats,and 50％ rats (5/10) experienced clinical manifestations of hepatic encephalopathy.Persistent fever over 7 days was showed in 10％ rats (1/10) of SFS group and 40％ rats (4/10) of TPIPSS group,respectively.The mean survival was superior in TPIPSS group (37.2 ± 23.5) d than SFS group (17.7 ± 13.5) d,P ＜ 0.05.Conclusion TPIPSS could be a safe and feasible approach to improve portal venous hypertension caused by SFS liver graft and hepatocellular reperfusion.
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Objective To analyze the retrieval of master and doctorial dissertations entitledsystematic review/meta analysis in domestic universities of traditional Chinese medicine. Methods Master and doctorial dissertations entitledsystematic review/meta analysis in domestic universities of traditional Chinese medicine retrieved from China Dissertation Full-text Database were analyzed using Excel and SPSS 17. 0,respectively. Results Of the 423 master and doctorial dissertations included in this study,71. 9% were retrieved from both Chinese and English databases, 27. 7% were retrieved from Chinese databases,82. 8% were retrieved from two or more Chinese databases,54. 1% were retrieved from two or more English databases. The most frequently retrieved Chinese database was CKNI, followed by VIP, CBM and Wanfang. The most frequently retrieved English database was PubMed, followed by Cochrane Library, EMBASE and OVID. Conclusion The low use of traditional Chinese medicine databases is the main prob-lem in retrieval of master and doctorial dissertations entitledsystematic review/meta analysis in domestic univer-sities of traditional Chinese medicine. No significant difference is found in retrieved doctorial dissertations and mas-ter dissertations between 211and non-211 universities of traditional Chinese medicine.