Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Background and aims:Inflammatory factors play significant roles in the development and occurrence of hepatocellular carcinoma(HCC).However,the tumor-protective functions of growth differentiation factors(GDFs)in HCC are yet to be clarified.In this study,we aimed to evaluate the expression levels of 10 GDFs in tumor and paratumor tissues from patients with HCC and perform in vitro and in vivo ex-periments to elucidate the role of GDF7 in regulating the proliferation and metastasis of HCC.Methods:The gene expression of 10 GDFs was compared between HCC and paratumors using The Cancer Genome Atlas dataset and patient-derived tissues.A tumor microarray containing 108 HCC tissue samples was used to explore the prognostic value of GDF7 expression.Loss-of-function experiments were also performed in vitro and in vivo to investigate the role of GDF7 in HCC.Results:The mRNA and protein levels of GDF7 were significantly lower in HCC tumors than in para-tumors(P＜0.001).Kaplan-Meier analysis showed that decreased GDF7 expression in HCC was asso-ciated with worse overall survival(5-year rate:61.8％vs.27.5％,P＜0.001)and increased recurrence risk(P＜0.001).Multivariate Cox regression analysis demonstrated that low GDF7 expression,the presence of microvascular invasion,and elevated alpha-fetoprotein(AFP)levels were independent risk factors for tumor recurrence and poor survival.Downregulation of GDF7 also increased the tumor growth in HCC cells and in an HCC xenograft model.GDF7 knockdown promoted migration and invasion via epithelial-mesenchymal transition.Meanwhile,a negative correlation between JunB proto-oncogene(JUNB)and GDF7 was observed in HCC tissues.Modulating JUNB levels altered GDF7 protein expression.Conclusions:GDF7 is a potential biomarker for predicting superior outcomes in patients with HCC.GDF7 amplification is a potential therapeutic option for HCC.

Traumatic rib fractures are the most common injury in thoracic trauma. Previously，the patients with traumatic rib fractures were mostly treated non-surgically，of which 50%，especially those combined with flail chest presented chronic pain or chest wall deformities and over 30% had long-term disabilities，being unable to retain a full-time job. In the past two decades，thanks to the development of internal fixation material technology，the surgical treatment of rib fractures has achieved good outcomes. However，there are still some problems in clinical treatment，including inconsistency in surgical treatment and quality control in medical services. The current consensuses on the management of regional traumatic rib fractures published at home and abroad mainly focus on the guidance of the overall treatment decisions and plans，and relevant clinical guidelines abroad lacks progress in surgical treatment of rib fractures in recent years. Therefore，the Chinese Society of Traumatology affiliated to Chinese Medical Association and Chinese College of Trauma Surgeons affiliated to Chinese Medical Doctor Association，in conjunction with national multidisciplinary experts，formulate the Chinese Consensus for Surgical Treatment of Traumatic Rib Fractures（2021）following the principle of evidence-based medicine，scientific nature and practicality. This expert consensus puts forward some clear，applicable，and graded recommendations from aspects of preoperative imaging evaluation，surgical indications，timing of surgery，surgical methods，rib fracture sites for surgical fixation，internal fixation methods and material selections，treatment of combined injuries in rib fractures，in order to provide references for surgical treatment of traumatic rib fractures.

Understanding the effect of immunosuppressive agents on intestinal microbiota is important to reduce the mortality and morbidity from orthotopic liver transplantation (OLT). We investigated the relationship between the commonly used immunosuppressive agent cyclosporine A (CSA) and the intestinal microbial variation in an OLT model. The rat samples were divided as follows: (1) N group (normal control); (2) I group (isograft LT, Brown Norway [BN] rat to BN); (3) R group (allograft LT, Lewis to BN rat); and (4) CSA group (R group treated with CSA). The intestinal microbiota was assayed by denaturing gradient gel electrophoresis profiles and by using real-time polymerase chain reaction. The liver histopathology and the alanine/aspartate aminotransferase ratio after LT were both ameliorated by CSA. In the CSA group, the numbers of rDNA gene copies of Clostridium cluster I, Clostridium cluster XIV, and Enterobacteriaceae decreased, whereas those of Faecalibacterium prausnitzii increased compared with the R group. Cluster analysis indicated that the samples from the N, I, and CSA groups were clustered, whereas the other clusters contained the samples from the R group. Hence, CSA ameliorates hepatic graft injury and partially restores gut microbiota following LT, and these may benefit hepatic graft rejection.

Objective To study the recurrence risks of viral hepatitis B (VHB) after liver transplantation for hepatitis B virus (HBV)-related liver diseases.Methods A total of 599 patients undergoing liver transplantation due to HBV-related liver disease [hepatic cellular cancer (HCC),decompensated liver cirrhosis (DLC),acute liver failure (ALF)] were included in this study.All patients included in this study have been followed up for at least 12 month for liver biochemistry and HBV testing,altogether with the clinic presentation and outcomes.Treatment protocols about prevention of VHB recurrence in perioperative period and after liver transplantation,the time interval and influence factors of VHB recurrence,and the disease prognosis were analyzed.Results Of the 599 patients,36 cases of VHB recurrence were observed.The rate of VHB recurrence was 7.2％ (23/319),5.6％ (13/232) and 0 (0/48) for HCC,DLC and ALF,respectively.The rates of VHB recurrence were 2.3％,5.5％,6％ for 1 year,5 years and 8 years,respectively.The rate of VHB recurrence in the lamivudine group was significantly higher than in enticavir group and combination therapy group [16.5％ (22/133),2.9％ (8/280),and 3.2％ (6/186),respectively,P＜0.05 for all].Conclusion HCC and DLC as liver transplant indications are independent risk factors for VHB recurrence after liver transplant.For liver transplant patients with HBV-related liver disease,entecavir monotherapy and combination therapy (lamivudine and adefovir,or tenofovir) are both more effective on the prophylaxis of VHB recurrence than lamivudine monotherapy.

Objective This study focused on the recurrence risks of viral hepatitis B (VHB) after liver transplantation for hepatitis B virus (HBV)-related liver diseases.Methods A total of 599 patients undergoing liver transplantation due to HBV-related liver disease [hepatic cellular cancer (HCC),decompensated liver cirrhosis (DLC),acute liver failure (ALF)] were included in this study.All patients included in this study have been followed up for at least 12 months for liver biochemistry and HBV testing,altogether with the clinical presentation and outcomes.Treatment protocols about prevention of VHB recurrence in perioperative period and after liver transplantation,the time interval and influencing factors of VHB recurrence,and the disease prognosis were analyzed.Results Of the 599 patients,VHB recurrence were observed in 36 cases.The rate of VHB recurrence was 7.2％ (23/319),5.6％ (13/232) and 0 (0/48) for HCC,DLC and ALF,respectively.The rate of VHB recurrence was 2.3％,5.5％ and 6％ for 1 year,5 years and 8 years,respectively.The rate of VHB recurrence in the lamivudine group was significantly higher than in enticavir group and combination therapy group [16.5％ (22/133),2.9％ (8/280),3.2％ (6/186),respectively,P ＜ 0.05].Conclusion HCC and DLC as liver transplantation indication are independent risk factors for VHB recurrance after liver transplantatuib.For liver transplantation patients with HBV-related liver disease,entecavir monotherapy and combination therapy (lamivudine and adefovir,or tenofovir are both more effective on the prophylaxis of VHB recurrance than lamivudine monotherapy.

BACKGROUND/AIMS: We aimed to evaluate the efficacy and safety of an immunosuppressive regimen without steroids after liver transplantation (LT) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: Sixty-six HCC patients who underwent an immunosuppressive regimen without steroids after LT were enrolled in the steroid-free group. The preoperative characteristics and postoperative outcomes of these patients were compared with those of 132 HCC recipients who were placed on an immunosuppressive regimen using steroids (steroid group). The incidence of acute rejection, HBV recurrence, infection, and new-onset diabetes mellitus and the overall and tumor-free survival rates were compared between the two groups. RESULTS: Differences were not observed in the 1-year (83.3% vs 97.0%, p=0.067), 3-year (65.4% vs 75.8%, p=0.067) or 5-year (56.3% vs 70.7%, p=0.067) patient survival rates or in the 1-year (62.1% vs 72.7%, p=0.067), 3-year (49.8% vs 63.6%, p=0.067) or 5-year (48.6% vs 63.6%, p=0.067) tumor-free survival rates between the two groups, respectively. In the steroid-free group, the patients who fulfilled the Milan criteria had higher overall and tumor-free survival rates than those in the steroid group (p<0.001). The prevalence of HBV recurrence (3.0% vs 13.6%, p=0.02) was significantly lower in the steroid-free group compared with the steroid group. CONCLUSIONS: After LT, an immunosuppressive regimen without steroids could be a safe and feasible treatment for HBV-related HCC patients, thus resulting in the reduction of HBV recurrence. Based on the observed survival rates, patients who fulfill the Milan criteria may derive benefits from steroid-free immunosuppression.
Carcinoma, Hepatocellular* ; Diabetes Mellitus ; Hepatitis B virus ; Humans ; Immunosuppression ; Incidence ; Liver Transplantation* ; Liver* ; Prevalence ; Recurrence ; Steroids ; Survival Rate

Objective Investigate the prognosis of patients undergoing liver transplantation (LT) for end-stage autoirnmune liver disease (ALD).Method The clinical data of 45 patients with endstage ALD undergoing LT from April 2001 to March 2015 in the first affiliated hospital of Zhejiang University were analyzed retrospectively.The postoperative cumulative survival rate of the recipients was calculated,and the causes of death were analyzed.The postoperative rejections,new onset viral hepatitis and ALD recurrence were also analyzed.Result In 45 ALD recipients,33 cases survived and the postoperative 5-year cumulative survival rate was 78.8％.Causes for 12 dead cases were mnultiple organ failure,liver graft failure,respiratory complications,hemorrhage and hepatic artery embolization.In 45 ALD recipients,6 cases suffered rejection after operation with the incidence bing 13.3％.One case suffered new onset hepatitis B infection 8 years after opcration.One recipient suffered primary disease (primary biliary cirrhosis) recurrence 2 years after operation,and 1 recipient with primary disease (primary sclerosing cholangitis) developed into overlap syndrome.They all survived for a long term after active treatments.Conclusion Most LT recipients with endstage ALD can obtain a long term survival.Attentions should be paid to the immunosuppressive regimens in early period after LT,prevention of infection,rejection and postoperative new onset viral hepatitis,and timely diagnosis of primary disease recurrence.

Objective To investigate the clinical value of transient elastography in adult after liver transplantation,by means of evaluating the correlation of liver stiffness measured by FibroScan with liver/renal functions.Method Forty-three patients received orthotopic liver transplant in our hospital during Dec.10,2013 and Mar.19,2014 were included in this study.Liver stiffness measurement (LSM) was performed after transplantation.Clinical data and laboratory tests including liver function and renal function were collected and analyzed.Result Bivariate correlation showed that body mass index (BMI),MELD score,graft-to-recipient weight ratio (GRWR) and warm ischemia time had no correlation with LSM.LSM at the 1st day after transplantation (LSM-1) showed no correlation with cold ischemia time,but LSM at the 7th day after transplantation (LSM-7) did,with R =0.335,P =0.028.LSM-1 showed positive correlation with the ICU time (R =0.488,P =0.001),but LSM-7 didn't.There was significantly positive correlation between LSM and aspartate aminotransferase,bile acid and creatinine,but no significant correlations were found between LSM and alanine arninotransferase,alkaline phosphatase,cholinesterase,gamma-glutamyl transferase,total bilirubin,direct bilirubin,indirect bilirubin,urea nitrogen and uric acid.The group with higher LSM-1 had longer ICU time than the lower group (9 d vs,7 d,P =0.013),and so was the hospital stay (34 d vs.23 d,P =0.023).For the LSM-7,there was no significant difference in ICU time and hospital stay between the two groups.The group with higher LSM-1 had higher serious complication incidence than the lower group (78.57％ vs.27.59％,P =0.002),but the two groups in LSM-7 showed no significant difference in serious complication incidence.Conclusion The LSM partially correlates with the liver function and renal function of liver transplantation recipient,and may have its clinical value for assessing the early prognosis after liver transplantation.

Objective To study the feasibility of using fractional flow reserve (FFR) to guide whether to perform coronary revascularization of non-culprit moderate stenosis in patients with unstable angina and estimate their clinical prognosis. Methods This study enrolled unstable angina patients with multivessel disease. First successful stenting of the culprit artery, then the other non-culprit moderate coronary stenosis were randomized into PCI guided by angiography or guided by FFR measurements. Death from any cause, nonfatal myocardial infarction, unplanned hospitalization leading to urgent revascularization and clinical manifestations with angina were followed during the first year. Results 71 patients were included, among them 35 patiens were randomly assigned to angiography-guided PCI and 36 patients to FFR-guided PCI. In FFR-guided PCI group, FFR was successfully measured in all of non-culprit moderate coronary stenosis. In 23 stenosis, the FFR was greater than 0.80, and stents were not placed in these stenosis. In 13 stenosis with FFR<0.8, stent were inplant and FFR was raised≥0.95 after stenting. The percentage of patients who had a primary end-point event was higher in the angiography-guided PCI group than the FFR-guided PCI group (P<0.05). Neither the rate of mortelity from any cause nor the rate of non-fatal myocardial infarction had significant difference between the 2 groups. Related to the target vessels rates of nonfatal myocardial infarction (5.6%vs. 28.6%) and target lesion revascularization (5.6%vs. 31.4%) were statistically different (P<0.01 and P<0.05, respectively). Conclusions In patients with unstable angina, it is safe to use FFR values to guide decisions on the revascularization of angiographically moderate non-culprit stenosis. Routine measurement of FFR in addition to angiographic guidance, as compared with PCI guided by angiography alone, results in a significant reduction in major adverse events at 1 year, particularly in urgent revascularization, and clinical manifestations with angina get better.