Novel mechanisms driving renal tubulointerstitial fibrosis / 中国临床药理学与治疗学

Renal fibrosis, especially tubulointerstitial fibrosis, is the most common pathway of all chronic kidney diseases progressing to end-stage renal diseases. Several adaptive reactions occur in renal tubular epithelial cells after chronic injury, such as changes in glycolipid metabolism, unfolded protein response, autophagy and senescence, epithelial-to-mesenchymal transition and G2/M cell cycle arrest. Maladaptive repair mechanisms can induce tubulointerstitial fibrosis. This article will discuss the molecular mechanism of these adaptive responses of renal tubular epithelial cells driving renal tubulointerstitial fibrosis, and provide a basis for exploring new drug targets for renal tubulointerstitial fibrosis.

Progress in quality management and control of donor organ procurement in foreign countries / 器官移植

Since the 20th century, organ transplantation has become a breakthrough technology to effectively save the lives of patients with end-stage organ failure, which has significantly enhanced the quality of life of patients. Organ donation is an important source of organ transplantation. Improving the quality of donor organ procurement is the key to promote the translation of donor organs and improve the prognosis of organ transplantation recipients. The United States, Spain and other countries have put forward a series of policies and standards in the quality management and control of donor organ procurement and achieved positive results. In this article, related concepts of medical quality management and control, advanced strategies and models of international donor organ procurement quality management, and quality control measures of Organ Procurement Organization, donors and donor organs were reviewed, aiming to provide reference for establishing a quality management and control system of donor organs with "Chinese characteristics" and advancing high-speed and high-quality development of donor organ procurement.

Chinese expert consensus on clinical application of inhibitors of mammalian target of rapamycin in liver transplant recipients (2023 edition) / 器官移植

@#The long-term survival and quality of life of liver transplant recipients largely depend on long-term health management and immunosuppression regimen after surgery. Long-term use of immunosuppressants may lead to severe complications, such as kidney injury, metabolic diseases and new malignant tumors, and even increase the risk of liver cancer recurrence after liver transplantation. At present, common immunosuppressive regimens in liver transplant recipients are delivered based on calcineurin inhibitor (CNI). However, renal toxicity, neurotoxicity and increased tumor recurrence caused by CNI have significantly affected clinical prognosis of the recipients. In recent years, the dosage of CNI has been gradually reduced and alternative drugs have been explored. Recently, the use of immunosuppressive regimens based on mammalian target of rapamycin inhibitor (mTORi) has been gradually increased. Multiple domestic and international guidelines have provided guidance on the use of mTORi in liver transplant recipients. China Organ Transplantation Development Foundation organized experienced transplant experts in China, combined with published guidelines, consensus and research progress at home and abroad and solicited extensive opinions to jointly formulate this expert consensus, aiming to provide reference for liver transplant clinicians in China.

Exploration of human resource management practice for organ donation coordinators in public hospitals / 中华医院管理杂志

The human resource management of organ donation coordinators in China is still in its infancy stage, plagued by such problems as unclear career orientation, poor management and unclear career planning. In March 2010, a tertiary public hospital was approved as a medical institution in a national pilot province for organ donation. In recent years, the hospital had kept exploring human resource management of coordinators and established a relatively complete management mode for organ donation coordinators. This mode featured the establishment of full-time recruitment positions, development of human resource management plans, refinement of job descriptions, establishment of performance evaluation plans, optimization of assessment and incentive mechanisms, and innovation of talent cultivation modes. The management practice had achieved certain results, ensuring the sustainable development of hospital organ donation operation, and providing a reference for the scientific and standardized development of organ donation and transplantation in China.

Regulation mechanism of post-translational modification of farnesoid X receptor / 中国临床药理学与治疗学

Farnesoid X receptor (FXR) is a nuclear receptor activated by bile acid that is involved in regulating gene expression related to bile acid, fat, glucose, and amino acid metabolism. The activity of FXR is regulated by a variety of post-translational modifications. Common post-translational modifications of FXR include O-GlcNAcylation, phosphorylation, acetylation, sumoylation, methylation, etc. These post-translational modifications may affect FXR binding of DNA and ligand, heterodimerization, and subcellular localization, and may specifically regulate downstream gene transcription and expression. Different post-translational modifications can lead to changes in FXR stability and biological function, which are closely related to the occurrence of diseases. This paper aims to review the post-translational modification of FXR in the past five years and the mechanisms involved in disease regulation, to explore the effects of post-translational modification on the physiological function of FXR and to provide a theoretical basis for mechanism research targeting FXR.

FXR agonist GW4064 ameliorates tacrolimus-induced abnormalities in glucose metabolism / 中国临床药理学与治疗学

AIM: To investigate the expression of glucose metabolism genes associated with tacrolimus-induced post-transplant diabetes in the mouse kidney and the mechanisms involved in the regulation of glucose metabolism by farnesylate X (FXR) receptor activator. METHODS: The gene expression levels of FXR, small heterodimeric partner-1 (SHP-1), phosphoenolpyruvate carboxykinase (PEPCK), and glucose transporter protein-2 (GLUT2) were measured after 72 h in HK-2 cell lines treated with tacrolimus and tacrolimus+FXR agonist (GW4064) and control groups, respectively. C57BL/6J male mice were gavaged with tacrolimus and tacrolimus+FXR agonist for 12 weeks, respectively, and the control group was given saline to observe the changes in body weight and blood glucose; after the animals were treated, the gene expression levels of FXR, SHP-1, PEPCK, and GLUT2 were detected, respectively. RESULTS: In cellular experiments, the expression of FXR, SHP-1 and GLUT2 genes was decreased in the tacrolimus-treated group (P< 0.05) and the expression of the PEPCK gene was significantly upregulated compared with the control group (P< 0.05). In animal experiments, compared with the control group, the blood glucose values were significantly increased in the tacrolimus-treated group and significantly decreased in the tacrolimus+FXR agonist combination intervention group (P< 0.05), and the expression of FXR, SHP-1 and GLUT2 genes were upregulated (P< 0.05) and the expression of PEPCK genes was significantly decreased in the mice kidney (P< 0.05).CONCLUSION: FXR agonists can improve tacrolimus-induced abnormal glucose metabolism after transplantation. Therefore, FXR may be a potential new target for the prevention and treatment of post-transplant diabetes.

Diagnostic criteria and research progress on Banff classification of allograft pathology in composite tissue allotransplantation / 器官移植

Composite tissue allotransplantation (CTA) is a novel transplantation discipline to treat functional tissue or limb defects. Since a majority of CTA grafts were vascularized grafts, it is also known as vascularized composite allotransplantation (VCA). The grafts of CTA/VCA consist of two or more types of allogeneic skin, subcutaneous tissue, bone, muscle, nerve and vessel, etc. Most of CTA/VCA grafts contain skin tissues, which possess the highest antigenicity. Acute rejection after transplantation is the primary obstacle leading to CTA/VCA graft failure and primary graft dysfunction. Hence, histopathological characteristics of skin rejection in CTA/VCA grafts have become the primary hotspot. In this article, pathological features of CTA/VCA rejection, Banff classification in 2007 and related research progress were reviewed, aiming to provide reference for the diagnosis and treatment of rejection and other complications of CTA/VCA.

Effect and potential molecular mechanism of FOXA2 on cell proliferation, migration and invasion of hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To investigate the effect of forkhead box protein A2(FOXA2) on cell proliferation, migration and invasion of hepatocellular carcinoma and the potential molecular mechanism.Methods:From January 2019 to December 2020, 10 cases of hepatocellular carcinoma patients from Zhongnan Hospital of Wuhan University were collected for study, including 7 males and 3 females, with an average age of 53 years. FOXA2 expression was detected in human liver cancer cell line, and the highest expression of FOXA2 was found in HepG2 cells transfected with FOXA2 overexpression plasmid. Immunohistochemistry and qRT-PCR were used to detect the expression of FOXA2. Western blot was used to detect the expression of FOXA2, hypoxia-inducible factor-1 α (HIF-1α), vascular endothelial growth factor A (VEGFA), B-cell lymphofactor-2 (Bcl-2), matrix metalloproteinase (MMP) 7, and glucose transporter (GLUT) 1. EdU assay was used to study cell proliferation, and Transwell chamber assay was used to study cell migration and invasion.Results:The relative expression of FOXA2 in liver cancer tissues were lower than those in adjacent tissues both at mRNA and protein levels, with statistical significance (both P<0.05). FOXA2 overexpression group showed lower cell proliferation rate (30.0±3.2)%, migration rate (10.6±1.1), and invasion rate (12.8±0.8) comparing with negative control group (67.0±3.6)%, (81.0±5.4), (74.8±4.5). The difference was statistically significant (all P<0.05). Expression of HIF-1α and its downstream targets VEGFA, MMP7, GLUT1 and Bcl-2 was decreased after over-expression of FOXA2 in HepG2 cells. Conclusion:FOXA2 inhibits proliferation, migration, and invasion in hepatocellular carcinoma by regulating HIF-1α signaling pathway, suggesting that FOXA2 is a potential target for the treatment of hepatocellular carcinoma.

Mechanism of CDK1 participates in the development of hepatocellular carcinoma and its inhibitor application value / 中国临床药理学与治疗学

Cyclin-dependent kinase 1 is a highly conserved serine/threonine kinase that acts as a checkpoint during mitosis, coordinating and promoting cell cycle progression. CDK1 is significantly upregulated in hepatocellular carcinoma. It is mainly related to p53 signal transduction pathway, LINC00346-miR-199a-3p-CDK1/CyclinB pathway, SNHG16/let-7b-5P/CDC25B/CDK1 pathway and UPF1-SNord52-CDK1 pathway. In this paper, the mechanism of CDK1 involvement in the occurrence and development of hepatocellular carcinoma was systematically elaborated, and the current situation of CDK1 inhibitor targeted treatment of HCC was clarified, which could provide clues and basis for the treatment of HCC with CDK1 as the target.

Two cases of liver transplantation donor withschistosomiasis and literature review / 中华器官移植杂志

Objective:There are few domestic reports of liver transplantation from schistosomiasis donors. Two schistosomiasis donor livers were employed for liver transplantation. The relevant experiences were summarized along with a literature review.Methods:Two unexpectedly discovered donor livers infected by schistosomiasis were successfully transplanted. And long-term follow-ups were conducted for recipients.Results:The recipients were followed up for 77 and 14 months respectively without recurrence.Conclusions:Non-cirrhotic donor livers infected with schistosome may safely employed for transplantation. A positive donor should be treated with praziquantel. However, a recipient has no indication for preventive deworming.

Advances in the preservation of steatotic liver graft / 中华肝胆外科杂志

More and more studies have been focusing on marginal donor livers, such as steatotic liver grafts, to alleviate donor shortage and reduce mortality from waiting lists. Poor tolerance of streatotic liver grafts often leads to primary graft nonfunction, early dysfunction, and postoperative vascular and biliary complications. Some studies have shown that moderate and severe macrosteatosis livers can be used for transplantation with rigorous selection of recipients. In this paper, techniques such as venous systemic oxygenated persufflation, hypothermic oxygenated perfusion, subnormothermic machine perfusion, normothermic machine perfusion, improved liver quality, and steatotic liver grafts transplantation were discussed.

Clinical retrospective analysis in delayed graft function morbidity of kidney transplantation recipients and gender factors in both donors and recipients / 中华器官移植杂志

Objective To explore the effects of donor/recipients' gender on delayed graft function (DGF) .Methods A retrospective analysis was performed for clinical data of donors (n=174) and recipients (n=265) during renal transplantation between May 1 ,2012 and December 31 ,2017 . Types of China donation after citizen's death ,age ,last creatinine level ,height ,weight ,body mass index (BMI) and protopathy of donors were collected .And pre-dialysis method ,dialysis time ,HLA mismatch ,post-creatine at Day 7 ,whether dialysis after transplantation ,height ,weight and BMI of recipients were analyzed .The data were checked by t and chi square tests and P<0 .05 was deemed as statistically significant .Results Donor gender had no correlation with DGF occurrence rate ( P=0 .689) while DGF occurrence rate among female recipients was evidently lower than that among males (P=0 .036);Female recipients selected peritoneal dialysis therapy more than male recipients (P=0 .023);Cerebral hemorrhage female donors were more than male donors (P= 0 .034);BMI (P<0 .001) and postoperative creatinine (P= 0 .001) among female recipients were evidently lower than that among males .Conclusions DGF occurrence rate is significantly lower among female receptors than that among males after kidney transplantation .

A case of nephrectomy with strong positive HLA antibody undergoing the third renal transplantation / 中南大学学报(医学版)

The positive human leukocyte antigen (HLA) antibody present in kidney transplant recipients affects both surgery and rejection, and also affects the long-term survival of the transplanted kidney. During the third kidney transplant, bilateral axillary fossa and iliac vessel were destroyed. It was very difficult for selection or separation of surgical vessels because the adhesions and scar formation was easy to damage blood vessels and intestinal tubes. A case with strong positive HLA antibody undergoing the third kidney transplant in our hospital was successfully solved the problems, such as less transplant space and vascular scar adhesion. Rituximab, rabbit anti-human thymocyte immunoglobulin, and methylprednisolone treated-antibodies were used in the operation. The immune function test was used to develop individualized treatment after the operation. The postoperative creatinine and urine volume tended to be stable, and the 16-month follow-up renal function was good.

Research advancement on the electric stimulation in the ischemia and reperfusion injury / 中华肝胆外科杂志

Ischemia and reperfusion injury has a serious effect on the organs’function. How to protect organs from injury and reduce organ damage during ischemia-reperfusion period is the main concerns of many researches. It is reported that electrical stimulation can alleviate ischemia and reperfusion injury of some organs. In this paper, we will review the effect of electric stimulation on organ ischemia-reperfusion injury and analyze the mechanism of electric stimulation and provide new ideas for the prevention and treatment of clinical organ ischemia-reperfusion injury.

Novel targets for ischemia reperfusion injury therapy in the liver / 中华肝胆外科杂志

Liver ischemia-reperfusion injury(IRI)is a major complication of hemorrhagic shock,liver transplantation.and other liver surgeries.It's important to study the targets towards liver IRI for preventing and mitigating the clinical renal injury.It has been reported that the peroxisome proliferator activated receptor gamma(PPARγ)protects the liver against IRI by targeting family with sequence similarity 3 member A(FAM3 A).At the meantime,noncoding RNAs,including lncRNAs and miRNAs,have also been reported to play important roles on the process of hepatic IRI.This review briefly discussed the roles and mechanisms of PPAR3,,FAM3A and noncoding RNAs in liver IRI,to find potential targets of gene ther-apy,aiming to prevent and mitigate the liver IRI as well as to improve postoperative liver function.

Advances in intervention measures for hepatic ischemia-reperfusion injury / 中华肝胆外科杂志

Hepatic ischemia-reperfusion injury is an inevitable clinical phenomenon during the liver transplantation. The mechanism of hepatic ischemia-reperfusion injury is complex, with reactive oxygen species, inflammatory factors, calcium overload, neutrophils and Kupffer cells involved. If injury continues to getting worsen, liver cells will undergo necrosis, apoptosis, and autophagy. Interventions for hepatic ischemia-reperfusion injury mainly include ischemic preconditioning, drug pretreatment, chemical pretreatment, mild hypothermia pretreatment, and machine perfusion and gene-targeted therapy in recent years. With the indepth research of injury mechanism, new intervention methods continue to emerge, which will bring new ideas for clinical prevention and treatment of liver ischemia-reperfusion injury.

Novel targets for ischemia reperfusion injury therapy in the liver / 中华肝胆外科杂志

Liver ischemia-reperfusion injury (IRI) is a major complication of hemorrhagic shock, liver transplantation, and other liver surgeries. It’s important to study the targets towards liver IRI for preventing and mitigating the clinical renal injury. It has been reported that the peroxisome proliferator activated receptor gamma (PPARγ) protects the liver against IRI by targeting family with sequence similarity 3 member A (FAM3A). At the meantime, noncoding RNAs, including lncRNAs and miRNAs, have also been reported to play important roles on the process of hepatic IRI. This review briefly discussed the roles and mechanisms of PPARγ, FAM3A and noncoding RNAs in liver IRI, to find potential targets of gene therapy, aiming to prevent and mitigate the liver IRI as well as to improve postoperative liver function.

170donors infection distribution and risk factor analysis of donor-derived infection in kidney transplantation / 中华器官移植杂志

Objective@#The epidemiological investigation of donor infection and the investigation of donor-derived infection(DDI)events in kidney transplantation to provide a basis for the prevention and treatment of donor infection and donor-derived infection events.@*Methods@#We retrospectively reviewed 170 donors and corresponding 316 kidney recipients between January 2014 with December 2017, pre-harvest blood, sputum, urine positive and negative culture were systematically recorded. We also collected donors/recipients demographics, transplant characteristics and recipients infection data within one month and focused on patient data of DDI events. Outcomes were followed up 6 months after surgery.@*Results@#Infection rate in 170 donors was 67.6 %, the positive rate of Gram-negative bacteria, Gram-positive bacteria and fungal were 48.3 %, 41.2 % and 10.4 %. Nine of 170 donors were DDI(5.29 %). Positive blood culture, urine culture and donor age were independent risk factors for DDI.@*Conclusions@#The incidence of donor infection is high. Although a few DDI events occur, the survival rate decreased. The positive blood culture and urine culture were important risk factors for the occurrence of DDI events. Therefore, it is necessary to focus on the monitoring of some high-risk strains and donors infected by high-risk infection sites.

170donors infection distribution and risk factor analysis of donor-derived infection in kidney transplantation / 中华器官移植杂志

Objective The epidemiological investigation of donor infection and the investigation of donor-derived infection(DDI)events in kidney transplantation to provide a basis for the prevention and treatment of donor infection and donor-derived infection events .Methods We retrospectively reviewed 170 donors and corresponding 316 kidney recipients between January 2014 with December 2017 ,pre-harvest blood ,sputum ,urine positive and negative culture were systematically recorded .We also collected donors/recipients demographics ,transplant characteristics and recipients infection data within one month and focused on patient data of DDI events .Outcomes were followed up 6 months after surgery .Results Infection rate in 170 donors was 67 .6 ％ ,the positive rate of Gram-negative bacteria ,Gram-positive bacteria and fungal were 48 .3 ％ ,41 .2 ％ and 10 .4 ％ .Nine of 170 donors were DDI(5 .29 ％ ) .Positive blood culture ,urine culture and donor age were independent risk factors for DDI .Conclusions The incidence of donor infection is high .Although a few DDI events occur ,the survival rate decreased .The positive blood culture and urine culture were important risk factors for the occurrence of DDI events . Therefore ,it is necessary to focus on the monitoring of some high-risk strains and donors infected by high-risk infection sites .

Injury of aldehyde dehydrogenase 2 in organ ischemia-reperfusion injury through autophagy / 中华肝胆外科杂志

With the rapid development of organ transplantation in China,the donation after cardiac death (DCD) donor organs are widely used.However,the quality of these organs is relatively poor,so the way to preserve and maintain organ still remains a severe problem.Among them,ischemic reperfusion injury (IRI) impairs the organs severely.Acetaldehyde dehydrogenase 2 (ALDH2) protects organs from stress conditions,including ischemia-reperfusion injury,and the activation and autophagy inhibition also protects the organs from stress conditions as well.Recent studies showed that ALDH2 can regulate autophagy to inhibit the organ injury during ischemia-reperfusion.Our study aims to discuss the new findings in this mechanism.