Pancreas最新文献

Objective: The protein arginine methyltransferase 5 (PRMT5) is a type II PRMT that is responsible for the majority of symmetric dimethylarginine (SDMA) in eukaryotic cells. While PRMT5 is overexpressed in pancreatic ductal adenocarcinoma (PDAC), the SDMA expression patterns in PDAC tissues have not been examined. This study is aimed to characterize the SDMA expression patterns in PDAC cells and patient tissues.

Methods: Tissue microarray (TMA), immunohistochemistry (IHC) of PDAC cell lines and archival PDAC tissue blocks, and western blotting were applied to this study.

Results: Expression of PRMT5 and SDMA is elevated in PANC-1 and MIA PaCa-2 cells compared with that in the pancreatic ductal HPNE cell line. Pharmacological inhibition of PRMT5 reduces the SDMA level, indicating that PRMT5 is primarily responsible for SDMA in PDAC cells. IHC staining of the TMA containing 158 patient samples demonstrates that nuclear SDMA staining is significantly enhanced in PDAC tissues compared to normal and tumor adjacent tissues. The elevated SDMA level is evident in tissues from patients with early-stage PDAC, which is further verified using the archival PDAC tissue blocks. In addition, the SDMA staining is highly clustered in the Islets of Langerhans of the pancreas, irrespective of the disease states.

Conclusions: We demonstrate for the first time that nuclear SDMA staining is significantly enhanced in PDAC tissues and in the Islets of Langerhans of the pancreas, indicating novel tissue IHC markers for PDAC and the endocrine units of the pancreas.

Objectives: Endoscopic retrograde cholangiopancreatography (ERCP) is widely utilized to manage pancreatobiliary diseases, but post-ERCP pancreatitis (PEP) is an unsolved issue. Although postprocedural elevation of serum amylase level is useful for early prediction of PEP, effectiveness of early interventions for hyperamylasemia has not been evaluated. Therefore, we conducted this study to elucidate the role of additional hydration in cases with hyperamylasemia after ERCP.

Materials and methods: This retrospective study included patients without a previous history of ERCP who developed hyperamylasemia 3 hours after the index ERCP in 2 centers. Patients were divided into a hydration group (with additional hydration of Lactated Ringer's solution at a rate of 40-80 mL/h) or a control group (without additional hydration). Using propensity score matching, clinical outcomes, including the incidence and severity of PEP, were compared between the matched hydration and control groups.

Results: A total of 399 patients were eligible for the current analysis and 109 patients for each group were selected after propensity score matching. Patient characteristics and endoscopic procedure details were well-balanced between the matched hydration and control groups. The incidences of overall PEP were not different between the 2 groups (42% vs. 45%, P =0.68), but the incidence of moderate or severe PEP was significantly lower in the matched hydration group (8.3% vs.22%, odds ratio 0.32; P =0.006). Hydration-related complication was not observed in both groups.

Conclusions: Additional hydration for patients with hyperamylasemia after ERCP reduced the incidence of moderate or severe PEP without a risk of volume overload.

Objectives: The purpose of this study is to evaluate the impact of animated pancreas patient (APP), pediatric-focused online educational modules on patient and caregiver education.

Methods: Retrospective study of collected APP metrics over 6 years. The audience reaches, and geographic location of the APP site were assessed. Further, we collected data on the top 5 viewed expert and patient videos and evaluated the impact of these modules on patient and provider education through viewer surveys.

Results: There were 226,772 visitors to the APP Pediatric modules on the NPF website over 6 years. They viewed the modules 310,068 times for an average of 51,678 views/year. In contrast, adult modules had 1,475,252 views over a 4-year period with an average of 368,813 views/year. Given the incidence of Pediatric and adult CP in 2014 of 1.9/100,000 persons and 24.7/100,000 persons, respectively, the average yearly views per incidence were 27,198 and 14,932 for children and adults, respectively. Eighty-nine percent of viewers of APP modules on pediatric pancreatitis who completed the feedback survey reported they learned new information.

Conclusion: The average yearly view/incidence for Pediatric modules was 1.8 times higher than for adult modules, with the majority reporting that they learned new information. The popularity of the Pediatric modules confirms that online educational content is highly accessible and successful in educating patients and caregivers about Pediatric pancreatitis and confirms the need to continue to utilize these educational modules now and in the future.

Objective: This study aims to assess the effectiveness of coupled plasma filtration and adsorption (CPFA) in patients with SAP through its effect on inflammatory mediators and sublingual circulating blood volume. The hypothesis put to test is that CPFA can achieve a satisfactory reduction in inflammatory mediators and enhance sublingual microcirculation in SAP with a very good clinical outcome.

Methods: A cohort of 112 SAP patients admitted to the ICU of our institution between January 2018 and December 2022 was consecutively recruited. Participants were randomized to the CPFA or the control group (standard treatment) using a random number table for assignment. Posttreatment alterations in inflammatory mediators and sublingual microcirculation were analyzed and compared.

Results: Following treatment, the study group showed significantly reduced levels of IL-1β, TNF-α, and IL-6 versus the control group. In addition, the study group witnessed lower serum and urinary amylase levels and APACHE II and SOFA scores. Parameters related to sublingual microcirculation, including total vessel density (TVDs), small vessel perfusion ratio (PPVs), perfusion small vessel density (PVDs), and microvascular flow index (MFIs), were significantly improved in the study group. Moreover, the study group observed lower rates of systemic inflammatory response syndrome (SIRS) and 30-day mortality versus the control group.

Conclusions: The application of CPFA in SAP patients effectively eliminates inflammatory mediators and enhances microcirculation, leading to improved clinical outcomes and reduced mortality rates.

Objective: This study aimed to explore the function of TNF receptor superfamily member 9 (TNFRSF9) in pancreatic ductal adenocarcinoma (PDA) by investigating its expression levels and functional implications in PDA cells.

Materials and methods: TNFRSF9 expression was evaluated in patients with PDA, and TNFRSF9 levels were manipulated in PDA cells to assess its effects on cell proliferation, migration, and apoptosis. The downstream target gene PAX6 was also examined. In vivo, studies in nude mice were performed to analyze the impact of TNFRSF9 overexpression on tumor growth.

Results: Analysis revealed decreased TNFRSF9 expression in PDA tissues. Ectopic TNFRSF9 expression in PDA cells suppressed cell proliferation and migration and induced apoptosis, while TNFRSF9 knockout showed opposing effects. PAX6 was identified as a downstream target of TNFRSF9. TNFRSF9 overexpression in nude mice led to reduced tumor growth.

Conclusion: The study suggests that TNFRSF9 may hold promise as a therapeutic target in PDA management, given its potential to inhibit tumor growth and modulate cell behavior.

Background: Pancreas transplantation (PTx) is a definitive therapy for patients with type 1 diabetes and advanced chronic kidney disease. Abdominal aortic calcification (AAC) is often observed in patients waiting for PTx and progresses according to the waiting period, but the impact of AAC on long-term outcomes remains unclear. In this study, we aimed to elucidate the impact of AAC on long-term outcomes.

Methods: We reviewed 65 consecutive PTx cases at our institution between April 2000 and November 2022 and enrolled 50 patients with simultaneous pancreas-kidney transplantation (SPK). AAC was assessed as AAC score by the Agatston method using multidetector computed tomography.

Results: Receiver operating characteristic curves were used to determine the cutoff value of the AAC score for death-uncensored pancreas graft survival; the area under the curve was 0.711 ( P =0.029). After dividing the patients into 2 groups according to the AAC cutoff, the dialysis period was significantly longer in the high AAC score group than in the low AAC score group ( P =0.001). Death-uncensored pancreas graft survival and patient survival after SPK were significantly lower in the high AAC score group than in the low AAC score group ( P =0.001, 0.001, respectively). In a Cox proportional hazards regression model, a high AAC score was independently associated with death-uncensored pancreas graft loss ( P =0.002).

Conclusions: AAC is associated with death-uncensored pancreas graft survival in patients undergoing SPK. Evaluation of AAC could be useful for predicting post-PTx prognosis.

Objectives: This study investigated the relationship between serum 25-Hydroxyvitamin D [25(OH)D] levels, vitamin D receptor (VDR) gene polymorphisms, and the prognosis of acute pancreatitis (AP).

Methods: This prospective observation study included patients with AP admitted to the Jinling Hospital between January 2018 and December 2019. Clinical information, laboratory tests, and single-nucleotide polymorphisms (SNPs) of the VDR gene were collected.

Results: A total of 508 AP patients were included, with a mean age of 44.81 ± 13.80 years. Among them, 158 (31.10%) cases developed sepsis, 211 (41.54%) cases had serious AP, and 47 (9.25%) patients died before discharge. The multivariate regression analysis showed that VD deficiency was an independent risk factor for the occurrence of sepsis (OR=3.768, 95% CI: 2.368-5.997, P <0.001), progression of AP patients to serious AP (OR=4.297, 95% CI: 2.806-6.582, P <0.001), and in-hospital mortality in AP patients (OR=2.406, 95% CI: 1.162-4.984, P =0.018). SNPs of VDR associated with sepsis, serious AP, or in-hospital death were identified, including rs12721375, rs2853559, rs11168287, rs2853559, and rs11168283 (all P <0.05). The Generalized Multifactor Dimensionality Reduction model analysis revealed that a 4-order model (rs11168283, rs11168287, rs2853559, and 25(OH)D) was the best model for predicting death ( P <0.01).

Conclusions: VD deficiency and VDR genetic polymorphisms are associated with AP prognosis in Chinese Han patients with AP. VDR genetic polymorphism may influence the outcomes of AP patients by affecting the levels of inflammatory cytokines.

Objectives: To elucidate the role of N-acetyltransferase 10 (NAT10) in pancreatic cancer (PC) progression and its epigenetic mechanisms, particularly in relation to metastasis.

Methods: TCGA and GTEx databases were used to analyze the expression and roles of NAT10 in pancreatic cancer. We constructed stable cell lines with NAT10 knockdown in PC cell lines, AsPC-1 and KPC. CCK-8, EdU assay, and colony formation assay were conducted to evaluate the capability of cell proliferation and clonogenesis in vitro. Meanwhile, a transwell assay was performed to assess the impact on invasion and metastasis abilities. The correlation between NAT10 and ZEB1 expression was verified by correlation analysis. The underlying mechanisms through which NAT10 regulates ZEB1 were confirmed by qPCR, western blot, RIP-qPCR, dot plot, and mRNA stability assay. Furthermore, the interplay among NAT10, ZEB1, and MT1-MMP was confirmed using similar experimental approaches. Rescue experiments involving ZEB1 overexpression further verified the role of NAT10/ZEB1/MT1-MMP axis in PC metastasis. In addition, the NAT10 inhibitor Remodelin was employed in a nude orthotopic PC model to investigate its effects on metastasis in vivo.

Results: NAT10 was found to be upregulated in PC and was significantly associated with poor prognosis. After NAT10 knockdown, the ability of proliferation and metastasis of AsPC-1 and KPC was remarkably impaired, the degree of ac4C modification was decreased, and the mRNA stability of ZEB1 declined. Correlation analysis indicated a positive correlation among NAT10, ZEB1, and MT1-MMP, and the results of qPCR and western blot also verified this conclusion. Moreover, ZEB1 overexpression could significantly reverse the inhibition of migration and invasion induced by NAT10 depletion in AsPC-1. NAT10 inhibitor Remodelin treatment could reduce the degree of peritoneal and liver metastases in vivo.

Conclusions: Our study highlights the pivotal functions of NAT10 in the progression of PC and reveals the underlying epigenetic mechanism that NAT10 promotes metastasis via ZEB1/MT1-MMP axis.

Objective: Managing painful chronic pancreatitis (CP) often involves invasive treatments, but success rates are variable. We aimed to describe the pain assessment tools used to measure the efficacy of endotherapy and surgery for painful CP and perform a meta-analysis of outcomes.

Design: PubMed, Embase, and Scopus databases were searched for published studies through April 1, 2023. Full papers in English that assessed pain outcomes among adults with painful CP undergoing invasive interventions were included.

Results: There were 413 out of 1,282 studies that underwent full-text review, and 279 studies were selected for the scoping review. Most commonly used pain assessment tools included symptom description (n=68 studies), numeric pain rating scales (NRS) or visual analog scales (VAS) (n=52), binary pain relief (yes or no) (n=27), and the pancreatitis-specific 4-item Izbicki score (n=28). In a meta-analysis of studies reporting preintervention and postintervention NRS or VAS (0-100), the mean decrease in pain after endoscopic intervention (n=9 studies) was 40.3 (95% CI: 27-53.6, P <0.001) and after surgical intervention (n=12 studies) it was 43.2 (95% CI: 31.5-54.9, P <0.001). A separate meta-analysis of studies reporting the preintervention and postintervention Izbicki score (n=5) showed similar findings. There was no difference in the change in pain scores between endotherapy and surgical cohorts in studies using NRS/VAS or Izbicki scores.

Conclusions: Pain outcomes were similar between endotherapy and surgery for painful CP based on the use of simple and highly variable pain assessment tools. Referral bias and sham effects need to be considered in future trials.