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Objective:To determine the risk factors of drainage time longer than 1 day in patients with selective abdominal drainage after laparoscopic cholecystectomy.Methods:The clinical data related to patients with selective abdominal drainage undergoing laparoscopic cholecystectomy from November 2009 to November 2019 at Chinese PLA General Hospital were retrospectively analyzed. Of 233 patients enrolled into this study, there were 147 males and 86 females, with a median aged 59.0 (47.5, 65.5) years old. The patients were divided into drainage time 1 day group of 65 patients and longer than 1 day group of 168 patients according to postoperative drainage time. The baseline data and perioperative data were collected, the risk factors correlated with drainage time longer than 1 day were analyzed.Results:The drainage time was 1 in the 1 day group and 2~8 in another group. Among the 233 patients, there was one with biliary leakage and 14 patients had abdominal bleeding, all of them healed after 2~3 days. All of the 233 patients were recovered when discharged. Independent risk factors related to drainage time longer than 1 day include BMI≥28 kg/m 2 ( OR=3.443, 95% CI: 1.411-8.405, P=0.007), operation time ≥65 min ( OR=2.570, 95% CI: 1.310-5.045, P=0.006), thickness of gallbladder wall ≥0.5 cm ( OR=12.720, 95% CI: 1.350-5.478, P=0.005), postoperative stomachache ( OR=13.537, 95% CI: 1.685-108.748, P=0.014) and postoperative fever ( OR=8.156, 95% CI: 1.035-64.249, P=0.046). Conclusion:For patients undergoing selective abdominal drainage after laparoscopic cholecystectomy with BMI ≥28 kg/m 2, operation time ≥65 min, gallbladder wall thickness ≥0.5 cm, postoperative abdominal pain and fever, clinicians should appropriately prolong the drainage time to ensure medical safety.
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Objective:To analyze the anti effect of chimeric antigen receptor (CAR)-T cells targeting hepatitis B surface antigen (HBsAg) on hepatocellular carcinoma cells.Methods:HBsAg-CAR gene was transduced into T cells (obtained from the blood of healthy donors) through a lentiviral vector. CD19-CAR-T cells were included as mock group, and untransduced T cells were included as control group. Cells of the three groups were co-cultured with hepatocellular carcinoma cells expressing HBsAg or not to detect the anti effect and releasing level of anti-tumor cytokines (tumor necrosis factor-α, interferon-γ, interleukin-2). Subcutaneous xenograft PLC/PRF/5 tumor model using NPG mice were established and HBsAg-CAR-T cells (experimental group, n=5) or untransfected T cells (control group, n=5) were injected through tail vein. Tumor volume was measured 15 days after injection. Results:HBsAg-CAR-T cells proliferation was good under in vitro culture, and the expression rate of CAR was stable. After co-cultured with hepatocellular carcinoma cells expressing HBsAg, the level of anti-tumor cytokines released by HBsAg-CAR-T cells was significantly higher than that of the other two groups of T cells, and the difference was statistically significant (all P<0.05); the anti rate of HBsAg-CAR-T cell group on HBsAg-positive hepatocellular carcinoma cells was significantly higher than that of the other two groups, and the difference was statistically significant (all P<0.05). The tumor volume of NPG mice in the experimental group was (250.8±62.8) mm 3, which was lower than that of the control group (757.5±102.6) mm 3, and the difference was statistically significant ( P<0.05). Conclusion:HBsAg-CAR-T cells can specifically recognize and kill HBsAg-positive hepatocellular carcinoma cells and release high level of anti-tumor cytokines.
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Advanced hepatocellular carcinoma has a high degree of malignancy and poor prognosis. Studies showed that there is a close relationship between the progression of hepatocellular carcinoma and the immune status in tumor microenvironment. Adoptive cell therapy showed anti-tumor effects and improve immunosuppression by infusing patients with activated specific immune cells, which become a central issue in tumor therapy and shown promising effects in the treatment of various malignant tumors, indicating great application potential. Adoptive cell therapy based on neoantigen may become a new hot spot in the treatment of hepatocellular carcinoma, and their application, safety and effectiveness evaluation, efficacy prediction and assessment have become urgent issues to be solved. The purpose of this article is to introduce the progress related to adoptive cell therapy for advanced hepatocellular carcinoma and elaborate the problems that need to be solved in the future.
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Objective:To establish a new bile duct injury and repair model in mice by generating bile duct distal stricture and proximal dilatation.Methods:The mice were randomly divided into sham operation group, bile duct stricture (BDS) group and bile duct ligation (BDL) group. The dilated bile duct of BDS mice was injured and then repaired 14 days after the modeling operation. Biochemical markers were detected and histopathological changes were analyzed.Results:14 days after the establishment of the model, the body mass in BDL group was significantly lower than that of the sham group ( P<0.05), while the body mass in BDS group was similar to sham group. Compared with the sham group, the bile duct and gallbladder of the BDS group and BDL group were both prominently dilated, but the sum of the diameters of bile duct and gallbladder in BDS group was significantly smaller than that in the BDL group ( P<0.05). Indocyanine green fluorescence imaging confirmed that biliary tract of BDS group could still drain bile. Serum ALT, AST and TBil levels in the BDS group were slightly higher than those in the sham group (all P<0.05), but significantly lower than those in the BDL group ( P<0.05). Bile ducts of BDS mice were injured by notching and repaired with bile duct path. 30 days after the repairing, HE staining showed that the bile duct epithelium around the patch was arranged in orderliness. Immunohistochemistry confirmed the positive staining of green fluorescent protein (EGFP) and CK19 in those groups. Conclusion:This model of bile duct injury and repair in mice can provide a new model for the study of the mechanism of bile duct injury and repair and the evaluation of tissue engineering bile duct.
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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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Objective The study systematically reviewed the therapeutic effect of the Kidney-Nourishing therapy on aromatase inhibitor-associated bone loss (AIBL).Methods The databases CNKI, CBM, VIP, Medline and the Cochrane Library were searched. Cochrane collaboration's tool for assessing risk of bias was adopted to assess the quality of trials. The Revman 5.3 software was used for the analysis on the outcome index such as bone minernal density and the level of serum estradiol.Results Meta-analysis was conducted on 11 randomly controlled clinical trials. All 11 studies were concducted in China, and the quality of researches was low. Meta-analysis revealed that the decrement of bone mineral density in the group receiving kidney-nourishing herbs was significantly smaller than that in the control group(P<0.001), theMD was -0.070, 95%CI was (-0.087, -0.053), but there was no significant difference between two groups in the outcome of the serum estradiol level (P=0.159), theMD was -2.622, 95%CIwas(-6.273, 1.030).Conclusion Kidney- Nourishing herbs can delay the process of aromatase inhibitor-associated bone loss, but may not influence the serum estrogen level.
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Objective To investigate the influence of double-effect activation of cholinergic antiinflammatory pathway on the liver injury and inflammatory response in obstructive jaundice rats by applying cholinesterase inhibitor and cholinergic M receptor blocker to activate alpha 7 nicotinic acetylcholine receptor.Methods 22 adult male Wistar rats were randomly assigned into three groups:sham operation (SO) group (n=6),bile duct ligation (BDL) induced obstructive jaundice with (BDL treatment group) or without treatment (BDL control group) (n=8 each).The medicine treatment group was given anisodamine (25 mg/kg) and neostigmine (25 μg/kg) daily via intraperitoneal injection after surgery,the control group was given equal amount of normal saline.The body weights of rats in each group were measured every other day.After 12 days,the rats were killed,and the pathological changes of liver injury,liver function and the expression levels of proinflammatory cytokines in the serum and liver tissue were observed.Results The body weight of BDL rats was significantly lower than the SO group rats,and the growth rate of BDL treatment group rats was the same as the rats in BDL control group 3 days after the starting of treatment.The AST,ALT,bilirubin and gamma-GT levels of BDL control and treatment groups were significantly higher than the SO group (P＜0.05),but there was no significant difference between BDL control and treatment groups.The serum albumin level of BDL treatment group was obviously higher than that of BDL control group,but the pathological liver injury was significantly slighter.The gene expression levels of TNF-alpha,IL-1 beta and IL-6 in the liver tissue were significantly higher in BDL groups than SO group (P＜0.05),but BDL treatment group was significantly lower than BDL control group (P＜0.05).In addition the serum TNF-alpha and IL-1 beta concentrations of BDL treatment group and control group were significantly higher than the SO group (P＜0.05),but the BDL treatment group was obviously lower than that BDL control group (P＜0.05).Conclusion The combine application of cholinesterase inhibitor and cholinergic M receptor blocker to activate the cholinergic anti-inflammatory pathway can significantly inhibit the obstructive jaundice induced proinflammatory gene expression and liver injury.
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Objective To develop rat models of graft cholangiopathies and evaluated their values.Methods Four groups were constructed.The long-term cold preservation group(n=24) contained homogeneic inbred rat liver orthotopic transplantations (ROLT) performed in a rat combination of ♂ Wistar→ ♂ Wistar with the donor liver preserved in 4℃ UW for 12 h,the vessels reconstructed by the two-cuff method,and the hepatic artery and extrahepatic bile duct rebuilt by a stent.The chronic rejection group (n=24)(CsA 1 mg · kg-1 · d-1,cold preserved for 1 h) was allogeneic inbred ♂ DA→♂ Lewis rats induced for ROLT,and the revascularization methods were the same as the longterm cold preservation group.The control group (n=24) (cold preserved for 1 h) was homogeneic inbred ♂ Wistar→♂ Wistar rats with ROLT techniques the same as above.The sham group (n=24)was ♂ Wistar rats that had an exploratory laparotomy.The animals were followed for 16 weeks,complications were compared,and liver tissues were harvested.Histopathological and morphometric techniques were used to construct a time course of histological changes after liver transplantation.Results In both the long-term cold preservation group and chronic rejection group,the rats recovered slowly,the incidence of complications and mortality were higher than those of other groups,and the intrahepatic bile duct proliferation and immune cell infiltration were noticeable after the operation.In 16 weeks,the hepatic lobules were separated by the proliferating bile ducts,the normal structure of hepatic lobules disappeared,many biliary epithelial cells necrosed with disappearing cytoplasms,and there was immune cell infiltration and obliterative arteriopathy.Conclusions The rat models of graft cholangiopathies induced by long-term cold preservation or chronic rejection donor livers are stable and easily standardized.This model is ideal for studying the pathogenesis and prevention of graft cholangiopathies.
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Objective In order to improve cirrhotic liver management,each aspect of the liver's complex blood flow must be understood.This study investigates the protective effect of portal vein occlusion,with hepatic artery preservation,on cirrhotic liver after ischemia and reperfusion.Methods Carbon tetrachlorideand induced cirrhotic rats and normal rats were randomly assigned into 4 groups:normal sham operation (N-SO),cirrotic sham operation (C-SO),portal triad clamping (PTC),and portal vein clamping without hepatic artery inflow control (PVC).During the occlusion,the total 3-minute blood loss from the liver surface cut was weighed.At 1,6,and 24 hours post reperfusion,the serum alapine amino transferas (ALT),the adenosine triphosphate (ATP) of liver tissue,the malonolialdehgde (MDA) of liver tissue,and the morphological changes were evaluated.Result The amount of hemorrhage between the groups ranked as follows:PTC ＜ PVC ＜ N-SO ＜ C-SO (P＜0.05).At 1,6,and 24 hours post reperfusion.the ALT and MDA levels of the groups ranked as follows:PTC ＞ PVC ＞ C-SO ＞ N-SO (P＜0.05).Additionally,each group's ATP level ranked as follows:PTC ＜ PVC ＜ C-SO ＜ N-SO (P＜0.05).With histopathological examination,the hepatic injuries of the PTC and PVC group were more severe than those of the C-SO group,especially in the PTC group.Conclusion Therefore,the technique of portal vein clamping and hepatic artery inflow control can reduce the ischemic reperfusion injury of the cirrhotic rats' liver.
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<p><b>OBJECTIVE</b>To observe the effect of congestion/reperfusion injury (CRI) and ischemia/reperfusion injury (IRI) on remnant liver in rats after hepatectomy.</p><p><b>METHODS</b>Male SD rats were divided into IRI, CRI, and control groups. In the former two groups, the left lateral lobe of the rats were subjected to IRI or CRI for 30 min with the rest lobes (about 70% of the total liver weight) resected; the rats in the control group received hepatectomy preserving only the left lateral lobe. The mortality rate of the rats was recorded, and the surviving rats were sacrificed at 1, 3 and 7 days after operation for analyses of ICG plasma disappearance rate (ICG-PDR), ALT, AST, liver regeneration rate, and Ki-67 labeling index.</p><p><b>RESULTS</b>The mortality rate was significantly higher in CRI group (34.3%) than in IRI group (8%, P<0.05) and control group (4%, P<0.01). On day 1 following hepatectomy, CRI group showed significantly higher liver enzyme levels and poorer liver functions than the control group (P<0.05) without significant differences from those in IRI group (P<0.05); Ki-67 labeling index in CRI group was significantly lower than that in the control group (P<0.01) and IRI group (P<0.01). Compared with the control group, CRI group showed a significantly lowered maximum Ki-67 labeling index with also a delayed occurrence (P<0.01); CRI resulted in poorer liver regeneration rate on day 3 after hepatectomy compared to the control group (P<0.01) and IRI (P<0.05).</p><p><b>CONCLUSION</b>Compared with IRI, CRI can result in severer liver damage and lowered liver regenerative capacity in rats early after hepatectomy.</p>
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Animals , Male , Rats , Hepatectomy , Liver Diseases , Liver Regeneration , Postoperative Period , Rats, Sprague-Dawley , Reperfusion InjuryABSTRACT
Objective To study the effects of a cirrhotic environment on the metastasis of liver cancer in mice.Methods Male BALB/c mice were randomly assigned to two groups:cirrhosis group and control group.The cirrhosis group was treated by an injection of carbon tetrachloride intraperitoneally.H22 liver cancer cells were directly implanted under the capsule of each group after cirrhosis was established.The animals were sacrificed at 1,2,and 3 weeks after the operation.The metastatic behavior of the cancer cells was observed by the naked eye and microscopically.Additionally,the adhesion ability of the liver was assessed by measuring the expression of vascular cell adhesion molecule 1 (VCAM-1),E-selectin,and E-cadherin.Results After the operation,the cirrhosis group showed an obvious metastatic tendency in both intrahepatic (14/19) and extrahepatic ways (4/19),compared with the control group's intrahepatic (5/17) and extrahepatic ways (1/17) (P＜0.05).Immunohistochemisty for VCAM-1 and E-selectin showed a significant increase in the cirrhosis (P＜0.05).However,there was no difference observed in the E-cadherin between the cirrhosis and control group.Conclusion A cirrhotic liver environment may promote the metastasis of liver cancer cells by increasing the ability of liver adhesion.