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Background: It is critical for every pancreatic surgeon to determine how to protect the aberrant hepatic artery intraoperatively in order to safely implement laparoscopic pancreatoduodenectomy (LPD). “Artery-first” approaches to LPD are ideal procedures in selected patients with pancreatic head tumors. Here, we described our surgical procedure and experience of aberrant hepatic arterial anatomy-LPD (AHAA-LPD) in a retrospective case series. In this study, we also sought to confirm the implications of the combined SMA-first approach on the perioperative and oncologic outcomes of AHAA-LPD. Methods: From January 2021 to April 2022, the authors completed a total of 106 LPDs, of which 24 patients underwent AHAA-LPD. We evaluated the courses of the hepatic artery via preoperative multi-detector computed tomography (MDCT) and classified several meaningful AHAAs. The clinical data of 106 patients who underwent AHAA-LPD and standard LPD were retrospectively analyzed. We compared the technical and oncological outcomes of the combined SMA-first approach, AHAA-LPD, and the concurrent standard LPD. Results: All the operations were successful. The combined SMA-first approaches were used by the authors to manage 24 resectable AHAA-LPD patients. The mean age of the patients was 58.1 ± 12.1 years; the mean operation time was 362 ± 60.43 min (325–510 min); blood loss was 256 ± 55.72 mL (210–350 mL); the postoperation ALT and AST were 235 ± 25.65 IU/L (184–276 IU/L) and 180 ± 34.43 IU/L (133–245 IU/L); the median postoperative length of stay was 17 days (13.0–26.0 days); the R0 resection rate was 100%. There were no cases of open conversion. The pathology showed free surgical margins. The mean number of dissected lymph nodes was 18 ± 3.5 (14–25); the number of tumor-free margins was 3.43 ± 0.78 mm (2.7–4.3 mm). There were no Clavien–Dindo III–IV classifications or C-grade pancreatic fistulas. The number of lymph node resections was greater in the AHAA-LPD group (18 vs. 15, p < 0.001). Surgical variables (OT) or postoperative complications (POPF, DGE, BL, and PH) showed no significant statistical differences in both groups. Conclusions: In performing AHAA-LPD, the combined SMA-first approach for the periadventitial dissection of the distinct aberrant hepatic artery to avoid hepatic artery injury is feasible and safe when performed by a team experienced in minimally invasive pancreatic surgery. The safety and efficacy of this technique need to be confirmed in large-scale-sized, multicenter, prospective randomized controlled studies in the future.

Hepatocellular carcinoma is one of the most common malignant tumors.M6A is a novel epigenetic modification that have been emerged as vital regulators for the progression of HCC. However, the regulatory role, clinical significance and the details of the modification, such as the impact on the local tumor environment, remain largely unclear. Our study showed that ALKBH5 was highly expressed in HCC and high ALKBH5 expression predicted a worse prognosis of HCC patients. Prediction of ALKBH5 function by tissue samples and single cell sequencing Gene Set Variation Analysis. Primary CD3 + T lymphocytes and bone marrow-derived macrophages were used to evaluate the effect of ALKBH5 on immune microenvironment. The results indicated that ALKBH5 promote HCC cell proliferation, metastasis and PD-L1+macrophage recruitment. Mechanistically the results showed that ALKBH5 regulates MAP3K8 expression in a m6A dependent manner which mediates the proliferation and metastasis of HCC cells. ALKBH5 also promotes the activation of JNK and ERK pathways through upregulating MAP3K8, thus regulating the expression of IL-8 and promoting macrophage recruitment. Taken together, these data show that ALKBH5 promotes HCC growth, metastasis and macrophage recruitment through ALKBH5/MAP3K8 axis and it may serve as a potential diagnostic marker and target for treatment of HCC patients.

Heterogeneity of antibody responses has been reported in SARS-CoV-2 vaccination recipients with underlying diseases. We investigated the impact of the presence of comorbidities on the humoral response to SARS-CoV-2 vaccination in patients with chronic disease (PWCD) and assessed the effect of the number of comorbidities on the humoral response to vaccination. In this study, neutralizing antibodies (NAbs) and IgG antibodies against the receptor-binding domain (RBD-IgG) were monitored following a full-course vaccination. In total, 1400 PWCD (82.7%, inactivated vaccines; 17.3%, subunit recombinant vaccine) and 245 healthy controls (65.7% inactivated vaccines, 34.3% subunit recombinant vaccine) vaccinated with inactivated or subunit recombinant SARS-CoV-2 vaccines, were included. The seroconversion and antibody levels of the NAbs and RBD-IgG were different in the PWCD group compared with those in the control group. Chronic hepatitis B (odds ratio [OR]: 0.65; 95% confidence interval [CI]: 0.46-0.93), cancer (OR: 0.65; 95% CI: 0.42-0.99), and diabetes (OR: 0.50; 95% CI: 0.28-0.89) were associated with lower seroconversion of NAbs. Chronic kidney disease (OR: 0.29; 95% CI: 0.11-0.76), cancer (OR: 0.38; 95% CI: 0.23-0.62), and diabetes (OR: 0.37; 95% CI: 0.20-0.69) were associated with lower seroconversion of RBD-IgG. Only the presence of autoimmune disease showed significantly lower NAbs and RBD-IgG titers. Patients with most types of chronic diseases showed similar responses to the controls, but humoral responses were still significantly associated with the presence of ≥2 coexisting diseases. Our study suggested that humoral responses following SARS-CoV-2 vaccination are impaired in patients with certain chronic diseases. This article is protected by copyright. All rights reserved.

Previous studies have shown that m6A is involved in many aspects surrounding tumor progression, but the role of classic m6A reading protein YTHDC1 in the progression and immune microenvironment among multiple cancers remains unclear. The aim of the present study was to investigate the role of YTHDC1 in the Pan cancer tumor progression and immune microenvironment. The YTHDC1 expression pattern and prognostic value were first detected in Pan cancer in the public data. The role of YTHDC1 in Pan cancer was analyzed by bioinformatic analysis. The association between YTHDC1 expression and immune cell infiltration and immune inhibitory markers was analyzed. The expression of YTHDC1 in hepatocellular carcinoma was verified by independent datasets and clinical samples, and its function was explored in vitro. YTHDC1 is positive expression in all of 33 types tumors, and its expression and phosphorylation modification have abnormal changes across varieties tumors based on the analysis of TCGA and CPTAC databases. Prognostic analysis also showed that YTHDC1 was closely related to the prognosis of patients in some tumors such as BLCA and KIRC (p

BACKGROUND: Postoperative pancreatic fistula is a common and serious complication following pancreaticoduodenectomy. Duct‐to‐mucosa pancreaticojejunostomy has been used in many centers to reconstruct pancreatic digestive continuity following pancreatoduodenectomy, however, its efficacy and safety are uncertain. OBJECTIVES: To assess the benefits and harms of duct‐to‐mucosa pancreaticojejunostomy versus other types of pancreaticojejunostomy for the reconstruction of pancreatic digestive continuity in participants undergoing pancreaticoduodenectomy, and to compare the effects of different duct‐to‐mucosa pancreaticojejunostomy techniques. SEARCH METHODS: We searched the Cochrane Library (2021, Issue 1), MEDLINE (1966 to 9 January 2021), Embase (1988 to 9 January 2021), and Science Citation Index Expanded (1982 to 9 January 2021). SELECTION CRITERIA: We included all randomized controlled trials (RCTs) that compared duct‐to‐mucosa pancreaticojejunostomy with other types of pancreaticojejunostomy (e.g. invagination pancreaticojejunostomy, binding pancreaticojejunostomy) in participants undergoing pancreaticoduodenectomy. We also included RCTs that compared different types of duct‐to‐mucosa pancreaticojejunostomy in participants undergoing pancreaticoduodenectomy. DATA COLLECTION AND ANALYSIS: Two review authors independently identified the studies for inclusion, collected the data, and assessed the risk of bias. We performed the meta‐analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes and the mean difference (MD) for continuous outcomes with 95% confidence intervals (CIs). For all analyses, we used the random‐effects model. We used the Cochrane RoB 1 tool to assess the risk of bias. We used GRADE to assess the certainty of the evidence for all outcomes. MAIN RESULTS: We included 11 RCTs involving a total of 1696 participants in the review. One RCT was a dual‐center study; the other 10 RCTs were single‐center studies conducted in: China (4 studies); Japan (2 studies); USA (1 study); Egypt (1 study); Germany (1 study); India (1 study); and Italy (1 study). The mean age of participants ranged from 54 to 68 years. All RCTs were at high risk of bias. Duct‐to‐mucosa versus any other type of pancreaticojejunostomy We included 10 RCTs involving 1472 participants comparing duct‐to‐mucosa pancreaticojejunostomy with invagination pancreaticojejunostomy: 732 participants were randomized to the duct‐to‐mucosa group, and 740 participants were randomized to the invagination group after pancreaticoduodenectomy. Comparing the two techniques, the evidence is very uncertain for the rate of postoperative pancreatic fistula (grade B or C; RR 1.45, 95% CI 0.64 to 3.26; 7 studies, 1122 participants; very low‐certainty evidence), postoperative mortality (RR 0.77, 95% CI 0.39 to 1.49; 10 studies, 1472 participants; very low‐certainty evidence), rate of surgical reintervention (RR 1.12, 95% CI 0.65 to 1.95; 10 studies, 1472 participants; very low‐certainty evidence), rate of postoperative bleeding (RR 0.85, 95% CI 0.51 to 1.42; 9 studies, 1275 participants; very low‐certainty evidence), overall rate of surgical complications (RR 1.12, 95% CI 0.92 to 1.36; 5 studies, 750 participants; very low‐certainty evidence), and length of hospital stay (MD ‐0.41 days, 95% CI ‐1.87 to 1.04; 4 studies, 658 participants; very low‐certainty evidence). The studies did not report adverse events or quality of life outcomes. One type of duct‐to‐mucosa pancreaticojejunostomy versus a different type of duct‐to‐mucosa pancreaticojejunostomy We included one RCT involving 224 participants comparing duct‐to‐mucosa pancreaticojejunostomy using the modified Blumgart technique with duct‐to‐mucosa pancreaticojejunostomy using the traditional interrupted technique: 112 participants were randomized to the modified Blumgart group, and 112 participants were randomized to the traditional interrupted group after pancreaticoduodenectomy. Comparing the two techniques, the evidence is very uncertain for the rate of postoperative pancreatic fistula (grade B or C; RR 1.51, 95% CI 0.61 to 3.75; 1 study, 210 participants; very low‐certainty evidence), postoperative mortality (there were no deaths in either group; 1 study, 210 participants; very low‐certainty evidence), rate of surgical reintervention (RR 1.93, 95% CI 0.18 to 20.91; 1 study, 210 participants; very low‐certainty evidence), rate of postoperative bleeding (RR 2.89, 95% CI 0.12 to 70.11; 1 study, 210 participants; very low‐certainty evidence), overall rate of surgical complications (RR 1.10, 95% CI 0.80 to 1.51; 1 study, 210 participants; very low‐certainty evidence), and length of hospital stay (15 days versus 15 days; 1 study, 210 participants; very low‐certainty evidence). The study did not report adverse events or quality of life outcomes. AUTHORS' CONCLUSIONS: The evidence is very uncertain about the effects of duct‐to‐mucosa pancreaticojejunostomy compared to invagination pancreaticojejunostomy on any of the outcomes, including rate of postoperative pancreatic fistula (grade B or C), postoperative mortality, rate of surgical reintervention, rate of postoperative bleeding, overall rate of surgical complications, and length of hospital stay. The evidence is also very uncertain whether duct‐to‐mucosa pancreaticojejunostomy using the modified Blumgart technique is superior, equivalent or inferior to duct‐to‐mucosa pancreaticojejunostomy using the traditional interrupted technique. None of the studies reported adverse events or quality of life outcomes.

Liver ischemia-reperfusion injury (IRI) is a major complication in the perioperative period and often leads to liver failure and even systemic inflammation. Previous studies have suggested that the inflammatory response participated in the liver damage during liver IRI. Nicotinamide phosphoribosyl transferase (NAMPT) is required for the maintenance of cellular nicotinamide adenine dinucleotide (NAD+) levels, catalyzing the rate-limiting step in the NAD + salvage pathway. NAMPT is strongly upregulated during inflammation and constitutes an important mechanistic link between inflammatory, metabolic, and transcriptional pathways. The aim of our study was to investigate the role of NAMPT in liver IRI.We investigated the effect of pharmacological inhibition of NAMPT with FK866 in models of liver IRI. Liver damage was assessed by HE staining, serum ALT/AST, and TUNEL staining. To examine the mechanism, primary hepatocytes, liver macrophages and RAW264.7 cells were treated with or without NAMPT inhibitors before hypoxia-reoxygenation. Liver macrophages and RAW 264.7 cells activation in vitro was evaluated by western blotting, flow cytometry, and ELISA.We found that NAMPT was upregulated in liver IRI. Treatment with the NAMPT inhibitor FK866 ameliorated liver IRI and suppressed inflammation in mice. Although NAMPT plays an important role both in hepatocytes and liver macrophages, we focused on the impact of NAMPT on liver macrophages. The mechanism revealed that FK866 potently inhibited NAMPT activity, as demonstrated by reduced liver NAD+ and intracellular NAD+, resulting in reduced abundance and activity of NAD + -dependent enzymes, including poly (ADP-ribose) polymerase 1 (PARP1), thus inhibiting macrophage M1 polarization by reducing CD86, iNOS, TNF-α, and interleukin (IL)-1β. Taken together, our data suggested that NAMPT can regulate macrophage polarization through NAD+/PARP1 to ameliorate liver injury, and that FK866-mediated NAMPT blockade may be a therapeutic approach in liver IRI.

In order to explore the molecular mechanism of acute rejection after liver transplantation (ARLT) in rats, we employed the GSE36798 data set in the Gene Expression Omnibust (GEO) database to construct a related ceRNA network. This dataset contained a total of 16 samples (8 graft samples and 8 plasma samples). Each kind of sample was divided into acute rejection (AR) groups and non-acute rejection (NR) groups, and each group had 4 replicates. First, we performed principal component analysis (PCA) with downloaded data to compare the difference between samples in a macroscopic way. Then, we used the "limma" R package to screen out differentially expressed miRNAs among different groups and used the "pheatmap" R package to perform bidirectional hierarchical clustering analysis for these differentially expressed miRNAs. The miRWalk database and the LncBase V.2 database were applied to predict downstream target genes and upstream-related lncRNAs, respectively. Meanwhile, the String database was used to predict the relationship between target genes, and the aforementioned results were processed for visualization by Cytoscape software. In addition, we exhibited the ultimate ceRNA network, including two lncRNAs, two miRNAs, and 77 mRNAs. Finally, we constructed a rat model of ARLT and applied graft specimens to relevant experimental verification. We found that the lncRNA Snhg1/rno-miR-139-5p axis might be involved in the regulation of ARLT in rats. In short, we demonstrated the differentially expressed miRNA profile, constructed a related ceRNA network, and screened out a possible regulatory axis. In view of the conservation of genes among species, this work was expected to provide a new strategy for the treatment and prevention of ARLT in the clinical setting.