HDAC inhibitors support long-term expansion of porcine hepatocytes in vitro.

Hepatocyte transplantation is an effective treatment for end-stage liver disease. However, due to the limited supply of human hepatocytes, porcine hepatocytes have garnered attention as a potential alternative source. Nonetheless, traditional primary porcine hepatocytes exhibit certain limitations in function maintenance and in vitro proliferation. This study has discovered that by using histone deacetylase inhibitors (HDACi), primary porcine hepatocytes can be successfully reprogrammed into liver progenitor cells with high proliferative potential. This method enables porcine hepatocytes to proliferate over an extended period in vitro and exhibit increased susceptibility in lentivirus-mediated gene modification. These liver progenitor cells can readily differentiate into mature hepatocytes and, upon microencapsulation transplantation into mice with acute liver failure, significantly improve the survival rate. This research provides new possibilities for the application of porcine hepatocytes in the treatment of end-stage liver disease.

A simple and efficient strategy for cell-based and cell-free-based therapies in acute liver failure: hUCMSCs bioartificial liver.

Acute liver failure (ALF) is a life-threatening condition. Cell-based and cell-free-based therapies have proven to be effective in treating ALF; however, their clinical application is limited by cell tumorigenicity and extracellular vesicle (EV) isolation in large doses. Here, we explored the effectiveness and mechanism of umbilical cord mesenchymal stem cells (hUCMSCs)-based bioartificial liver (hUCMSC-BAL), which is a simple and efficient strategy for ALF. D-galactosamine-based pig and mouse ALF models were used to explore the effectiveness of hUCMSC-BAL and hUCMSC-sEV therapies. Furthermore, high-throughput sequencing, miRNA transcriptome analysis, and western blot were performed to clarify whether the miR-139-5p/PDE4D axis plays a critical role in the ALF model in vivo and in vitro. hUCMSC-BAL significantly reduced inflammatory responses and cell apoptosis. hUCMSC-sEV significantly improved liver function in ALF mice and enhanced the regeneration of liver cells. Furthermore, hUCMSC-sEV miRNA transcriptome analysis showed that miR-139-5p had the highest expression and that PDE4D was one of its main target genes. The sEV miR-139-5p/PDE4D axis played a role in the treatment of ALF by inhibiting cell apoptosis. Our data indicate that hUCMSC-BAL can inhibit cytokine storms and cell apoptosis through the sEV miR-139-5p/PDE4D axis. Therefore, we propose hUCMSC-BAL as a therapeutic strategy for patients with early ALF.

Effects of machine perfusion strategies on different donor types in liver transplantation: a systematic review and meta-analysis.

BACKGROUND: The increasing use of extended criteria donors (ECD) sets higher requirements for graft preservation. Machine perfusion (MP) improves orthotopic liver transplantation (OLT) outcomes, but its effects on different donor types remains unclear. The authors' aim was to assess the effects of hypothermic machine perfusion (HMP), normothermic machine perfusion (NMP), or normothermic regional perfusion (NRP) versus static cold storage (SCS) on different donor types. MATERIALS AND METHODS: A literature search comparing the efficacy of MP versus SCS in PubMed, Cochrane, and EMBASE database was conducted. A meta-analysis was performed to obtain pooled effects of MP on ECD, donation after circulatory death (DCD), and donor after brainstem death. RESULTS: Thirty nine studies were included (nine randomized controlled trials and 30 cohort studies). Compared with SCS, HMP significantly reduced the risk of non-anastomotic biliary stricture (NAS) [odds ratio (OR) 0.43, 95% confidence interval (CI) 0.26-0.72], major complications (OR 0.55, 95% CI 0.39-0.78), and early allograft dysfunction (EAD) (OR 0.46, 95% CI 0.32-0.65) and improved 1-year graft survival (OR 2.36, 95% CI 1.55-3.62) in ECD-OLT. HMP also reduced primary non-function (PNF) (OR 0.40, 95% CI 0.18-0.92) and acute rejection (OR 0.62, 95% CI 0.40-0.97). NMP only reduced major complications in ECD-OLT (OR 0.56, 95% CI 0.34-0.94), without favorable effects on other complications and survival. NRP lowered the overall risk of NAS (OR 0.27, 95% CI 0.11-0.68), PNF (OR 0.43, 95% CI 0.22-0.85), and EAD (OR 0.58, 95% CI 0.42-0.80) and meanwhile improved 1-year graft survival (OR 2.40, 95% CI 1.65-3.49) in control DCD-OLT. CONCLUSIONS: HMP might currently be considered for marginal livers as it comprehensively improves ECD-OLT outcomes. NMP assists some outcomes in ECD-OLT, but more evidence regarding NMP-ECD is warranted. NRP significantly improves DCD-OLT outcomes and is recommended where longer non-touch periods exist.

Stereotactic Body Radiotherapy Versus Surgery for Early-Stage Non-Small-Cell Lung Cancer.

BACKGROUND: Surgery is the gold standard therapy for patients with early-stage non-small-cell lung cancer (NSCLC). However, stereotactic body radiotherapy (SBRT) may provide as an alternative for patients who are medically inoperable or refuse surgical resection. The optimal treatment (SBRT or surgery) for patients with early-stage NSCLC is not clear. METHODS: A systematic search was performed from PubMed, MEDLINE, Embase, and the Cochrane Library. Study heterogeneity and publication bias were estimated. RESULTS: Fourteen cohort studies involving 1438 participants (719 who received SBRT and 719 who received surgery) were included in the meta-analysis. The main bias sources between the two groups, such as age, gender, tumor diameter, forced expiratory volume in 1 s, and Charlson comorbidity index were matched. The surgery was associated with a better overall survival (OS) and long-term distant control (DC) for early-stage NSCLC. The pooled OR and 95% confidence interval (CI) for 1-y, 3-y, 5-y OS, and 5-y DC were 1.56 (1.12-2.15), 1.86 (1.50-2.31), 2.43 (1.80-3.28), and 2.74 (1.12-6.67), respectively. No difference was found between the treatments in the 1-y and 3-y disease-free survival; 1-y, 3-y and 5-y locoregional control; or 1-y and 3-y DC. CONCLUSIONS: Our results found a superior OS and long-term DC for early-stage NSCLC after surgery compared with SBRT after propensity score matching.

Endovascular stent-graft exclusion of adult giant patent ductus arteriosus through a hybrid transabdominal approach.

Endovascular stent-graft exclusion has proven to be a safe and effective alternative for adult patients with patent ductus arteriosus. We present a case of a 38-year-old woman with a large, symptomatic ductus. However, her small femoral and iliac arteries limited the access options. The patient underwent laparotomy and end-to-side anastomosis of a Dacron graft to the abdominal aorta. Then, the laparotomy was temporarily closed with the graft externalized, and the patient was transported to the radiology suite for successful stent-graft deployment. This hybrid transabdominal approach may be preferred in patients without suitable peripheral arteries to accommodate the device.