Liquid-liquid phase separation(LLPS)is a reversible process,during which biological macromolecules,including proteins and nucleic acids,condense into liquid membraneless organelles under the influence of weak multivalent interactions.Currently,fluorescence recovery after photobleaching is the primary method used to detect the phase separation of biological macromolecules.Recent studies have revealed the link between abnormal LLPS and the pathogenesis and development of various human cancers.Through phase separation or abnormal phase separation,tumor-related biological macromolecules,such as mRNA,long noncoding RNAs(lncRNAs),and tumor-related proteins,can affect transcriptional translation and DNA damage repair,regulate the autophagy and ferroptosis functions of cells,and thus regulate the development of various tumors.In this review,we summarized the latest research findings on the mechanism of LLPS in the pathogenesis and progression of tumors and elaborated on the promotion or inhibition of autophagy,tumor immunity,DNA damage repair,and cell ferroptosis after abnormal phase separation of biomolecules,including mRNA,lncRNA,and proteins,which subsequently affects the pathogenesis and progression of tumors.According to published findings,many biological macromolecules can regulate transcriptional translation,expression,post-transcriptional modification,cell signal transduction,and other biological processes through phase separation.Therefore,further expansion of the research field of phase separation and in-depth investigation of its molecular mechanisms and regulatory processes hold extensive research potential.

The article provides a brief review of the risk factors, prevention, and management strategies for kidney injury after non-kidney solid organ transplantation, in order to optimize the management of kidney injury by the transplant team and further improve the life quality and survival of the recipients.

Objective:To explore the microbiological characteristics of donor blood culture and donor liver perfusion culture and summarize the clinical experiences to provide basic rationales for preventing donor-derived infections.Methods:From August 1, 2018 to November 26, 2018 and November 27, 2018 to December 31, 2020 at First Affiliated Hospital, Zhengzhou University, culture results of donor blood and donor liver perfusate were retrospectively reviewed.According to whether or not donor liver was obtained without breaking diaphragm, removing gallbladder intraoperatively and flushing bile through cystic duct, two stages were assigned: before and after improvement measures of liver donor, i.e.August 1, 2018 to November 26, 2018 and November 27, 2018 to December 31, 2020.The culture results of donor blood samples and donor liver perfusion fluid samples in two stages of liver transplantation were statistically analyzed and infection preventing measures during donor liver maintenance and obtaining donor liver examined.Results:A total of 486 cases of blood culture from potential donors and 478 cases of liver perfusion culture were analyzed.The results showed that the incidence of blood culture infection was 4.5% and 4.3% before and after improvement measures( χ2=0.008; P=0.927)while the incidence of perfusion fluid infection was 56.8% and 46.2%( χ2=4.569; P=0.031); Klebsiella pneumoniae was a major pathogen cultured in perfusion solution before improvement measures and Staphylococcus epidermidis after improvement measures. Conclusions:Before organ donation, infection screening and prevention of potential donors and corresponding measures during donor liver acquisition can reduce donor source infection and effectively lower the mortality of recipients.

Objective:To summarize the strategies and effects of portal vein reconstruction after liver transplantation in recipients with diffuse portal vein thrombosis(PVT).Methods:Clinical data were retrospectively reviewed for 10 PVT patients undergoing liver transplantation(LT)from January 2014 to June 2019. There were 8 males and 2 females with a age of (50.7±10.1)years. The follow-up period was (66.3±25.8)months. Diameter of portal vein anastomosis, diameter and flow velocity of portal vein and presence of ascites were evaluated by color Doppler ultrasound. And computed tomography(CT)was employed for assessing the presence of esophagogastric varices. And patency of portal vein blood flow, therapeutic outcomes of portal hypertension and survival status of recipients were evaluated.Results:Among 7 patients with diffuse PVT without enlarged collaterals, cavoportal hemitransposition( n=6) and renoportal anastomosis( n=1) were performed.Ascites subsided gradually and minimal ascites( n=4) perdisted.Variceal bleeding did not recur within 6 months.As of December 2021, portal vein blood flow remained unobstructed in 4 recipients and 3 patients died.One case of inferior vena cava thrombosis and renal injury at 3 months post operation died of multiple organ failuer at 8 months post-operation.Another patient died of recurrent hepatocarcinoma at 11 months post-operation.Another case died of stroke at 44 months post-operation.Among 3 patients with diffuse PVT complicated with enlarged collaterals, there were right gastric vein to portal vein anastomosis( n=1), gastric coronary vein to portal vein anastomosis( n=1) and pericholedochalvarix to portal anastomosis( n=1). Ascites gradually subsided within 2 months post-operation.Portal vein anastomosis thrombosis was formed 1 month after operation and racanalizated after anticogulation and thrombosis therapies in patient with gastric coronary vein to portal vein anastomosis.Upper gastroinstestinal hemorrhage occurred 36 months after operation and was relieved by endoscopic ligation and sclerotherapy.Blood flow of portal vein was unobstructed in patients with right gastric vein and pericholedochalvarix to portal vein anastomosis.During the last follow-up, velocity of portal vein surpassed 20 cm/s and liver function remained normal in 7 survivors. Conclusions:For patients with complex PVT, portal vein reconstruction may ensure sufficient portal vein blood flow of graft. After operation, portal hypertension disappears and liver function normalizes.

Liver transplantation is an effective treatment for the end-stage liver disease. However, hepatic ischemia-reperfusion injury (HIRI) will inevitably occur during liver transplantation, which might lead to early graft dysfunction or aggravate rejection. The underlying protective mechanism remains to be further elucidated. Programmed cell death is an important mechanism of HIRI, and multiple novel types of programmed cell death participate in the pathological process of HIRI. In-depth study of programmed cell death is expected to further improve the therapeutic effect of liver transplantation. In this article, research progresses on apoptosis, autophagy and autophagy-dependent cell death, ferroptosis, necroptosis, pyroptosis, pathanatos and other common programmed cell death patterns in HIRI were reviewed, aiming to provide reference for enhancing the success rate of liver transplantation and improving clinical prognosis of the recipients.

Objective:To study the risk factors for acute kidney injury (AKI) after adult orthotopic liver transplantation.Methods:The clinical data of 232 recipients who underwent orthotopic liver transplantation at the First Affiliated Hospital of Zhengzhou University from January 2019 to April 2021 were retrospectively analyzed. There were 195 males and 37 females, aged (49.1±9.4) years old. The patients were divided into two groups according to whether AKI had occurred within 7 days of surgery into the AKI group ( n=112) and the non-AKI group ( n=120). Clinical data including basic information, preoperative hematological indexes, operation time and postoperative hospital stay were compared between the two groups. Factors associated with AKI after orthotopic liver transplantation were studied using univariate analysis and those factors with significant differences were included in multifactorial logistic regression analysis. Results:Among 232 patients who underwent orthotopic liver transplantation, 112 patients developed AKI after surgery, with an incidence of 48.3% (112/232). There were 64 patients with AKI stage 1 (57.1%, 64/112), 30 patients with AKI stage 2 (26.8%, 30/112), and 18 patients with AKI stage 3 (16.1%, 18/112). Logistic regression analysis showed that hypertension ( OR=5.874, 95% CI: 1.931-17.863, P=0.002) and high scores on the model for end-stage liver disease (MELD) ( OR=1.041, 95% CI: 1.010-1.074, P=0.010) were independent risk factors for AKI after orthotopic liver transplantation. Conclusion:Hypertension and MELD score were independent risk factors for postoperative AKI in orthotopic liver transplant recipients.

Objective To investigate the expression of ENO3 gene in hepatocellular carcinoma and its effect on the sensitivity of hepatocellular carcinoma cell lines to OXA, and to explore the possible mechanism. Methods qRT-PCR and immunohistochemical analysis were used to detect the expression of ENO3 in 48 pairs of hepatocellular carcinoma tissues and normal liver tissues.Overexpression plasmid was constructed and transfected into MHCC97H and HepG2 cells.The experiments were divided into empty group (Vector group), ENO3 overexpression group (ENO3 group), empty+OXA group (Vector+OXA group) and ENO3 overexpression+OXA group (ENO3+OXA group).The proliferation ability of MHCC97H and HepG2 cells were detected by CCK-8 assay and cell colony formation assay.The apoptosis rate was determined by flow cytometry assay.Protein expressions of Bcl-2, Bax and Caspase-3 were detected by Western blot assay. Results The expression of ENO3 was significantly decreased in hepatocellular carcinoma tissues, compared with normal liver tissues adjacent to the carcinoma.The expression of ENO3 gene in the ENO3 overexpression group was significantly higher than that in the empty group.Compared with the Vector+OXA group, cell viability was decreased, apoptosis rate was increased, Bcl-2 protein expression was decreased, Bax and Caspase-3 protein expression were increased in the ENO3+OXA group. Conclusion The expression of ENO3 is down-regulated in hepatocellular carcinoma tissues, and the overexpression of ENO3 can enhance the sensitivity of hepatocellular carcinoma cell lines to oxaliplatin by promoting cell apoptosis.

Liver cancer is one of the common malignant tumors in China, and the treatment effect is poor. The current treatment plan is still surgery-based comprehensive treatment, and multidisciplinary combined therapy is currently the main mode of liver cancer treatment. With the increased number of new technologies and methods of liver cancer treatment being applied clinically, the prognosis of liver cancer patients has significantly improved. This article explains the selection mechanism for optimal individualized combined treatment plans to improve the curative effect of liver cancer treatment based on the different conditions of liver cancer patients and types of liver cancer.

Objective:To develop an ex vivo normothermic mechanical perfusion(NMP)and compare the effect of different portal perfusion pressures on attenuating hepatic injury from donor after cardiac death(DCD).Methods:All rat livers were subjected to in situ warm ischemia for 30 min after cardiac attest and thereafter stored for 8 h under cold preservation. Six livers were harvested and regarded as static cold storage(group CS, n=6). In experimental group, liver received an ex vivo dual NMP with oxygenated perfusion via hepatic artery for 2 h after cold storage. Hepatic injury was assessed and compared from perfused livers with full portal vein pressure(group M1, n=6)and low portal vein pressure(group M2, n=6). The evaluation parameters included perfusion flow, liver enzymes of perfusate, pathological changes by hematoxylin-eosin staining, Suzuki histological criteria, expression of activation markers of polymorphonuclear neutrophils and macrophages, myeloperoxidase (MPO)and CD68 by immunohistochemistry, level of malondialdehyde(MDA)and activity of superoxide dismutase(SOD). Results:In experimental group during NMP, perfusion flows tended to increase when portal pressures were stabilized in groups M1 and M2.Perfusion flow during NMP 60~120 min was significantly higher than during NMP 0~20 min.After NMP with full portal pressure, hepatic sinusoidal congestion, hepatocyte necrosis, steatosis and Suzuki criteria were lower in group M1 than those in group CS( P<0.05). Compared with group M1, lower hepatic injury was characterized with a lower change of liver enzymes in perfusate( P<0.05), a better histological evaluation( P<0.05), a lower level of MDA and a higher activity of SOD( P<0.05), lower expressions of CD68 and MPO ( P<0.05)and lower levels of TNF-α and IL-6( P<0.05)in perfused liver. Conclusions:The ex vivo dual NMP with oxygenated perfusion via hepatic artery mimics liver perfusion under the physiological conditions.NMP with a lower portal pressure can attenuate hepatic ischemia-reperfusion injury and confer a better protection against liver damage from DCD.

Objective: The aim of this study is to evaluate the commutability of 16 processed materials for 17-hydroxyprogesterone by using 2 commutability assessment approaches. Methods: 52 serum specimens were collected in Clinical Laboratory Department of Beijing Hospital from February 2018 to June 2019. According to the report of the Clinical and Laboratory Standards Institute (EP14-A3) document and the recommendations of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) working group on commutabilityassessment, serum 17-hydroxyprogesterone isotope diluent chromatogram tandem mass spectrometry (ID-LC/MS/MS) was used for comparison. Three clinical routine analysis systems (1 radioimmunoassay, 2 LC/MS analysis methods) were used to determine the concentration of 17-hydroxyprogesterone in 52 human serum samples and 16 processed materialsfor commutabilityassessment. Results: Combined with the results of the two commutability assessment, all accuracy verification materials and national steroid hormone standards showed good commutability in the LC/MS analysis system, and 6/9 EQA materials showed commutability in the three routine analysis systems.All materials showed good commutability in the LC/MS analysis system of bias difference method. Conclusions The two kinds of commutability assessment results are different. Bias difference method has more clinical value, but it has certain application limitations. The use of fresh frozen human serum as a quality assessment materialfor serum 17-hydroxyprogesterone is meets the commutability requirement.