【Abstract】 Objective To investigate the protective role of recombinant human growth hormone (rhGH )in ischemic reperfusion injury of rat liver and its mechanism. Methods One hundred Male rats were randomly divided into two groups: the rhGH group and the control group. In the rhGH group, rhGH were injected （0.2U/100g weight） to rats seven days before the ischemic reperfusion injury, and in the control group, normal saline was injected instead. Serum levels of ALT， TNF-α and IL-1α were tested. Hepatic tissue was sectioned for to detect the level of EC and MDA, the expression of NF-κB and ICAM-1 mRNA on SEC. Ultrastructural characteristics histopathological characteristics were determined also. Results Serum levels of ALT, TNF-α, IL-1α and the contents of MDA in the control group were significantly higher than those in the rhGH group （P＜0.05）. Comparied with control group, rhGH also decreased NF-κB activation, and reduced the expression of ICAM-1 mRNA of SEC in the liver cells （P＜0.05）. Electronic microscopic revealed that the hepatic sinusoidal endothelial cells and the hepatocellular mitochondria were injured in the control group. Pretreatment with the rhGH was able to significantly improved the pathological changes. Conclusion rhGH might confer the protection to ischemic reperfusion injury of rat liver through reducing the expression of NF-κB to down-regulate cytokine (IL-1α,TNF-α), MDA and inhibition the expression of ICAM-1 mRNA.
ObjectiveTo summarize the current research status of the relationship between DNA methylation and liver regeneration.MethodThe related literatures at home and abroad were searched to review the studies on relationships between the methylation level of liver cells, regulation of gene expression, and methylation related proteins and liver regeneration.ResultsThe DNA methylation was an important epigenetic regulation method in vivo and its role in the liver regeneration had been paid more and more attentions in recent years. The existing studies had found the epigenetic phenomena during the liver regeneration such as the genomic hypomethylation, methylation changes of related proliferating genes and DNA methyltransferase and UHRF1 regulation of the liver regeneration.ConclusionsThere are many relationships between DNA methylation and liver regeneration. Regulation of liver regeneration from DNA methylation level is expected to become a reality in the near future.
Objective To investigate the joint effects of selective digestive decontamination (SDD) and glutamine (Gln) on preventing intestinal bacterial translocation of orthotopic piggyback liver transplantation and to observe the incidence of postoperative pneumonia in rabbit. Methods Thirty rabbits received orthotopic piggyback liver transplantation and were randomly divided into three groups (SDD group, SDD+Gln group and control group). Mixed emulsion of tobramycin, polymyxin E and nystatin were given to the rabbits in SDD group. Same dosage of the above components plus Gln were given to the rabbits in SDD+Gln group. Samples of portal vein blood, ileum tissue and lung tissue were obtained in each group at different phases during and after operation, the pathological changes of ileum tissue, the bacterial translocation in blood of portal vein and the incidence of postoperative pneumonia were detected. Results The mixing section area of intestinal blood capillaries in SDD+Gln group was smaller compared with control group (P＜0.05， P＜0.01) and SDD group (P＜0.05) while the portal vein was obstructed for 15, 30 and 45 min, and after the operation, respectively. The length of ileum villus in SDD+Gln group was longer than that in control group (P＜0.05) and in SDD group (P＜0.05) before the portal vein was obstructed, but the length of ileum villus in control group gradually became longer and eventually exceeded that in SDD+Gln group at the time of 45 min after the portal vein was obstructed (P＜0.05). After the operation, the length of ileum villus in SDD+Gln group was significantly longer than that in SDD group (P＜0.05) and control group (P＜0.01). At the time of 45 min after the obstruction of portal vein and 30 hours after operation, the positive rate of cultured bacterial in the blood of portal vein in SDD+Gln group was significantly lower than that in control group (P＜0.05, P＜0.01). The incidence of postoperative pneumonia in SDD+Gln group and SDD group were significantly lower than that in control group (P＜0.05,P＜0.01). Conclusion Gln could nourish intestinal epithelium of mucous membrane.When combined with SDD, it could decreased the incidence of intestinal bacterial translocation occurred during the obstruction of portal vein and after operation, so as to decrease the incidence of postoperative pneumonia.
Objective To research the effects of recombinant growth hormone (rhGH) with total parenteral nutrition (TPN) on nitrogen balance and nutritional state of the patients following major abdominal surgery. Methods We randomly selected 45 patients receiving TPN after major abdominal surgery and distributed them to study group (rhGH+TPN, n＝30) and control group (TPN only, n＝15). For 7 days after operation, every one was given rhGH 4u or replaced by hypodermic injection of normal saline (control group). Results TPN+rhGH promoted the rehabilitant of nitrogen balance, heightened the level of plasma albumin and transferrin and increased the weight and creatinin/height index (CHI), but the thickness of triceps skin fold (TSF) had no significant change in patients following major abdominal surgery. Conclusion The rhGH can improve the effects of TPN.
Objective To establish a stable model of orthotopic liver transplantation (OLT) using donation after cardiac death (DCD) in rat, and to analyze death causes within 24 h after OLT, then explore appropriate treatment strategies for it. Methods The heart arrested 10 min before liver graft harvesting. The rat OLT model using DCD was performed by Kamada two-cuff technique. The operative time and death were recorded. Results One hundred OLT models using DCD were performed successfully within 40 d, the donor operative time was (20±5) min, the recepient operative time was (55±5) min, the anhepatic phase was (20±3) min. Nine rats were died during the operation, including 4 cases of massive haemorrhage, 1 case of anesthesia accident, 1 case of longer anhepatic phase, 1 case of sleeve implant failure, and 2 cases of aeroembolism. Twenty-two rats died within 12 h after the operation, including 6 cases of intestinal necrosis, 6 cases of anastomotic bleeding, 3 cases of pulmonary edema, 4 cases of intraoperative massive haemorrhage, 2 cases of vascular embolism, and 1 case of unexplained death. Nineteen rats died 12–24 h after the operation, including 9 cases of intestinal necrosis, 3 cases of anastomotic bleeding, 2 cases of pulmonary edema, 1 case of intraoperative massive haemorrhage, 1 case of vascular embolism, and 3 cases of unexplained death. Conclusions There are many reasons resulting in early death of rat OLT using DCD, postoperative intestinal necrosis, intraoperative and postoperative bleeding, and postoperative pulmonary edema are main causes. For these reasons, prevention and improvement measures are helpful to establish a stable model and improve a successful rate of rat OLT using DCD.
ObjectiveTo summarize the role of ionized free calcium/calmodulin/calmodulin-dependent protein kinase Ⅱ (Ca2+/CaM/CaMKⅡ) signaling pathway in liver fibrosis so as to provide a theoretical basis for the treatment of liver fibrosis. MethodThe recent literature relevant research on the role of Ca2+/CaM/CaMKⅡ signaling pathway in the process of liver fibrosis both domestically and internationally was reviewed. ResultsThe Ca2+/CaM/CaMKⅡ signaling pathway played a bidirectional regulatory role in the process of liver fibrosis, potentially facilitating the activation of hepatic stellate cells and triggering hepatocyte apoptosis through synergistic transforming growth factor-β1 and platelet-derived growth factor pathways. ConclusionsAt present, there is very little research on the role of Ca2+/CaM/CaMKⅡ signaling pathway in the process of liver fibrosis, and there is still insufficient understanding. Future research should focus on the mechanism of this signaling pathway in liver fibrosis, especially its upstream genes or downstream target proteins, which will aid to develop targeted and effective treatment strategies, achieve the reversal of liver fibrosis and even liver cirrhosis, and provide more effective treatment options for patients with liver fibrosis.
【Abstract】Objective To explore the changes of expression of AFP mRNA in human hepatocellular carcinoma （HCC） tissues after oral Xeloda therapy.Methods Total RNA was extracted from HCC tissue samples collect after operation and nested reverse transcription polymerase chain reaction （RT-nested PCR） assay was performed to determine the expression of AFP mRNA in this study.Results The final product of AFP mRNA amplified by RT-PCR was 174 bp and by RT-nested PCR was 101 bp. The AFP mRNA is positive in 12 of 21 patients (positive rate 57.14%) amplified by RT-nested PCR assay in Xeloda treatment group which is much lower than control group: 18 of 20 patients (positive rate 90.00%),P＜0.05.The serum AFP value of Xeloda treatment group 〔(23.2±12.8) μg/L〕 is much lower than that of control group 〔(39.6±24.3) μg/L〕 four weeks after operation (P＜0.05). However, There was no difference between two groups in serum AFP value before operation.Conclusion Xeloda can effectively suppress the expression of AFP mRNA in human HCC tissues and lower it’s product serum AFP value.The clinical application of Xeloda in HCC patients deserve further study.
Objective To summarize the diagnosis and treatment progress of borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) in recent years. Methods Through the retrieval of relevant literatures, the progress in the diagnosis and treatment of BR-PDAC in recent years were reviewed, to summarize the current status of definition, management, and outcome of BR-PDAC. Results Pancreatic surgery had significantly changed during the past years and resection approaches had been extended beyond standard procedures, including vascular and multivisceral resections. Consequently, BR-PDAC, which had recently been defined by the International Study Group for Pancreatic Surgery (ISGPS), had become a controversial issue with regard to its management in terms of upfront resection vs. neoadjuvant treatment and sequential resection. The key point was preoperative diagnostic accuracy to define the resectability of BR-PDAC and radical tumor resection followed by neoadjuvant treatment. Conclusion Surgery followed by neoadjuvant treatment is the only treatment option for BR-PDAC with the chance of long-term survival.
ObjectiveTo understand the current research status of calorie restriction and calorie restriction mimetics in inflammatory diseases. MethodThe literatures about the effect of caloric restriction and caloric restriction mimetics on immune cells, inflammatory responses, and clinical applications were reviewed and analyzed. ResultsAs a dietary therapy, the caloric restriction affected the immune system and function by limiting daily energy intake, regulating cellular metabolic pathways and energy patterns, reducing the inflammatory reaction and improving body symptoms. A growing numbers of attention had been paid in aging, type 2 diabetes, cardiovascular disease, osteoarthritis, neurodegenerative diseases, etc. And it was found that some caloric restriction mimetics such as resveratrol, rapamycin, metformin, etc. could not only achieve similar effects with caloric restriction, but also did not need to strictly restrict diet. ConclisionsAlthough calorie restriction has been studied extensively, there is still no widely accepted and uniform calorie restriction protocol, which is challenging in clinical practice. The development of calorie restriction mimetics, which has similar effects to calorie restriction without requiring strict dietary restriction, is more in line with human physiology and is advantageous to patients. There is a certain understanding how these drugs can prevent inflammation by regulating metabolic pathways, and the relation between them is complex. In future, the knowledge proposed in new field of immunometabolism is preferred to prevent inflammation in age-related diseases, and anti-inflammatory drugs should be reused as a therapeutic option for treatment of age-related diseases.
Objective To study the mechanism of immune hyporesponsiveness of allograft rejection induced by transfusion nonpufsed allopeptide syngeneic immature dendritic cell (imDC) generated from recipient bone marrow progenitors and to explore a possible strategy for liver allograft protection in clinic. Methods Forty experimental rats were randomly divided into 4 group: control group, cyclosporine A (CsA) group, mature DC (mDC) group and imDC group. In control group, Wistar rats only received liver transplantation. In CsA group, Wistar rats underwent liver transplantation plus CsA treatment 〔10 mg/（kg·d)〕. In mDC group, recipient-derived mDC 1×106 were infused intravenously through the penile vein to Wistar rats. In imDC group, ImDC with the dose of 1×106 were injected into Wistar rats via the dorsum vein of penile. In each group, five recipients were killed on the 10th day after transplantation, the other five recipients were left to observe survival time. The levels of ALT, AST, TBIL, IL-2, IFN-γ, IL-4 and IL-10 were detected. The acute rejection and the expression of FasL/Fas in the grafts were detected by HE and immunohistochemical staining. Western blot was used to detect Scurfin protein expression of CD4+ CD25+ T cells. Results The median survival time of the liver allografts in CsA group and imDC group were significantly longer than that in control group and mDC group ( P ＜ 0.05). The levels of ALT and TBIL in control group and mDC group were significantly higher than those in CsA group and imDC group ( P ＜ 0.05). Compared with CsA group and imDC group, the levels of IL-2 and IFN-γ were higher but the levels of IL-4 and IL-10 were lower in control group and mDC group ( P ＜ 0.01). Slightly or no rejection reaction was found in CsA group and imDC group ( P ＜ 0.05). The Scurfin protein expressions of CD4+ CD25+ T cells of imDC group were significantly higher than those of other three groups. Conclusion Application of nonpufsed allopeptide syngeneic recipient-derived imDC is an effective way to induce immune hyporesponsiveness by blocking indirect recognition in rat liver transplantation model. Survival span is significantly prolonged by its protective effect. The mechanism of immune hyporesponsiveness induced by imDC transfusion might be involved in some aspects: T cell apoptosis, immune deviation of Thl/Th2 cytokine net and inhibition of T lymphocytes responsiveness by regulatory T cells.