A retrospective analysis of the clinical efficacy of pancreatic duct stent implantation in the management of acute biliary pancreatitis requiring ERCP.

BACKGROUND: This study aimed to investigate the feasibility, effectiveness, and safety of pancreatic duct stenting in managing acute biliary pancreatitis (ABP) necessitating endoscopic retrograde cholangiopancreatography (ERCP). It further aimed to provide valuable insights for subsequent clinical diagnosis and treatment. METHODS: This research employs an observational retrospective case-control study design, encompassing patients with ABP who underwent ERCP at the hepatobiliary surgery department of the General Hospital of Ningxia Medical University between August 1, 2018, and December 31, 2020. A total of 229 cases were screened based on inclusion and exclusion criteria. Regardless of ABP severity, patients were categorized into the stent group (141) and the non-stent group (88). Changes in blood amylase (Amy), lipase (LIP), leukocyte count (WBC), total bilirubin (TBIL), alanine aminotransferase (ALT), hematocrit (HCT), and creatinine (CR) were compared between the two groups. Moreover, variables such as recovery time for oral feeding, hospitalization duration, hospitalization costs, local complications, systemic complications, and new organ failure were recorded to assess the therapeutic effect of pancreatic duct stenting. RESULTS: No significant differences were observed in gender, age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, ABP severity grade, organ failure (OF), cholangitis, or biliary obstruction between the pancreatic stent and non-stent groups (P > 0.05). There was no significant difference in the incidence of complications related to acute pancreatitis between the two groups (P > 0.05). The median fasting and hospitalization times of patients in the stent group were significantly shorter than those in the non-stent group (P < 0.05). No significant differences between the groups were observed in hospitalization costs and in-hospital mortality (P > 0.05). There were no significant variations in white blood cell (WBC) count, TBIL, ALT, and creatinine (Cr) at admission, 72 h, and in the differences between the two groups (P > 0.05). The levels of Amy at admission and 72 h in the stent group were significantly higher than those in the non-stent group (P < 0.05). The differences in LIP and HCT in the stent group were considerably higher than in the non-stent group (P < 0.05). Although no significant differences were observed in mean Amy and LIP between the two groups (P > 0.05), the mean 72-h HCT in the stent group was 38.39% (95% confidence interval [CI] 37.82%-38.96%) was lower than that in the non-stent group (39.44%, 95% CI 38.70-40.17%) (P < 0.05). CONCLUSION: In the stent group, feeding time and hospital stay were significantly shorter than those in the non-stent group. No significant differences were observed between the two groups in the incidence of complications and mortality. The HCT value decreased more rapidly in the stent group. Early pancreatic stent implantation demonstrated the potential to shorten the eating and hospitalization duration of patients with ABP, facilitating their prompt recovery. TRIAL REGISTRATION: This study was registered as a single-center, retrospective case series (ChiCTR1800019734) at chictr.org.cn.

Immunotoxicity Evaluation of Trihalophenolic Disinfection By-Products in Mouse and Human Mononuclear Macrophage Systems: The Role of RNA Epitranscriptomic Modification in Mammalian Immunity.

BACKGROUND: 2,4,6-Trichlorophenol (TCP), 2,4,6-tribromophenol (TBP) and 2,4,6-triiodophenol (TIP) are three widely detected trihalophenolic disinfection by-products (DBPs). Previous studies have mainly focused on the carcinogenic risk and developmental toxicity of 2,4,6-trihalophenols. Very little is known about their immunotoxicity in mammals. OBJECTIVES: We investigated the effects of 2,4,6-trihalophenols on mammalian immunity using a mouse macrophage model infected with bacteria or intracellular parasites and aimed to elucidate the underlying mechanisms from an epitranscriptomic perspective. The identified mechanisms were further validated in human peripheral blood mononuclear cells (PBMCs). METHODS: The mouse macrophage cell line RAW264.7 and primary mouse peritoneal macrophages were exposed to different concentrations of TCP, TBP, and TIP. The pro-inflammatory marker Ly6C, the survival of the bacterium Escherichia coli (E. coli), and the parasite burden of Toxoplasma gondii (T. gondii) were assessed. Furthermore, the global gene expression profiling of macrophages following exposure to 2,4,6-trihalophenols was obtained through RNA-sequencing (RNA-seq). The effects of 2,4,6-trihalophenols on RNA N6-methyladenosine (m6A) methyltransferases and total RNA m6A levels were evaluated using Western blotting and dot blot, respectively. Transcriptome-wide m6A methylome was analyzed by m6A-seq. In addition, expression of m6A regulators and total RNA m6A levels in human PBMCs exposed to 2,4,6-trihalophenols were detected using quantitative reverse transcriptase polymerase chain reaction and dot blot, respectively. RESULTS: Mouse macrophages exposed to TCP, TBP, or TIP had lower expression of the pro-inflammatory marker Ly6C, with a greater difference from control observed for TIP-exposed cells. Consistently, macrophages exposed to such DBPs, especially TIP, were susceptible to infection with the bacterium E. coli and the intracellular parasite T. gondii, indicating a compromised ability of macrophages to defend against pathogens. Intriguingly, macrophages exposed to TIP had significantly greater m6A levels, which correlated with the greater expression levels of m6A methyltransferases. Macrophages exposed to each of the three 2,4,6-trihalophenols exhibited transcriptome-wide redistribution of m6A. In particular, the m6A peaks in genes associated with immune-related pathways were altered after exposure. In addition, differences in m6A were also observed in human PBMCs after exposure to 2,4,6-trihalophenols. DISCUSSION: These findings suggest that 2,4,6-trihalophenol exposure impaired the ability of macrophages to defend against pathogens. This response might be associated with notable differences in m6A after exposure. To the best of our knowledge, this study presents the first m6A landscape across the transcriptome of immune cells exposed to pollutants. However, significant challenges remain in elucidating the mechanisms by which m6A mediates immune dysregulation in infected macrophages after 2,4,6-trihalophenol exposure. https://doi.org/10.1289/EHP11329.

PABPC1 promotes cell proliferation and metastasis in pancreatic adenocarcinoma by regulating COL12A1 expression.

BACKGROUND: The expression of cytoplasmic poly (A) binding protein-1 (PABPC1) has been reported in multiple cancer types. This protein is known to modulate cancer progression. However, the effects of PABPC1 expression in pancreatic adenocarcinoma (PAAD) have not been investigated. Here, we investigate the regulatory targets and molecular mechanisms of PABPC1 in PAAD. METHODS: PABPC1 and collagen type XII α1 chain (COL12A1) expression in PAAD and their role in tumor prognosis and tumor stage were investigated using The Cancer Genome Atlas database analysis. After silencing PABPC1, messenger RNA sequencing and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. The expression of differentially expressed genes (DEGs), cell viability, apoptosis, and cell migration and invasion were explored using reverse transcription-quantitative polymerase chain reaction, Cell Counting Kit-8 assay, flow cytometry assay, and transwell assay, respectively. The relationship between PABPC1 and COL12A1 expression was assessed by Pearson's correlation analysis. The regulatory function of COL12A1 in PABPC1-affected BXPC3 cell behavior was studied after COL12A1 was overexpressed. RESULTS: PABPC1 and COL12A1 expression was upregulated in patients with PAAD and was linked to poor prognosis. Four hundred and seventy-four DEGs were observed in BXPC3 cells after PABPC1 silencing. GO and KEGG analyses revealed that the top 10 DEGs were enriched in cell adhesion pathways. Additionally, PABPC1 silencing inhibited cell viability, migration, and invasion and accelerated apoptosis in BXPC3 cells. PABPC1 silencing increased AZGP1 and ARHGAP30 expression and decreased CAV1 and COL12A1 expression in BXPC3 cells. PABPC1 positively mediated COL12A1 expression, whereas PABPC1 knockdown induced the inhibition of BXPC3 cell proliferation, migration, and invasion. CONCLUSION: The results of this study indicate that PABPC1 may function as a tumor promoter in PAAD, accelerating BXPC3 cell proliferation and metastasis by regulating COL12A1 expression.

Distribution analysis of positive and negative pathogenic bacteria in patients with acute pancreatitis and the clinical characteristics and model prediction analysis of positive infection bacteria.

Background: There were bacteria in the early pancreatic juice culture of severe acute pancreatitis (SAP) patients, but during the clinical time, some patients showed more positive bacteria and some patients showed more negative bacteria. Many scholars have different test results, and further clinical research needs to be carried out to clarify this fact. To determine evidence of infection in the early stage of acute pancreatitis (AP) by pancreatic juice bacterial culture and provide a reference for the anti-infective therapy of AP. Methods: Patients with AP who underwent pancreatic juice bacterial culture in the Department of hepatobiliary surgery of the General Hospital of Ningxia Medical University from January 1, 2019 to June 30, 2020were reviewed. Endoscopic retrograde cholangiopancreatography (ERCP) was used to collect pancreatic juice, which was sent to the laboratory for culturing. The clinical data and bacterial culture results of the patients were then recorded and analyzed. According to the results of the pancreatic juice culture, the patients were divided into a positive bacterial culture group (n=64) and a negative bacterial culture group (n=92). It was compared the data results of two groups [age, gender, etiology, acute physiology and chronic health evaluation (APACHE) II score, cultured bacteria, complications, local complications, Balthazar computed tomography (CT) score, inflammatory factors, the use of antibiotics, drug sensitivity analysis results, and the patient's co-infection] and performed multivariate analysis to identify the clinically valuable indicators. Moreover, a receiver operating characteristic (ROC) curve was drawn to predict the model of positive pancreatic juice culture in AP. Results: The patients in the positive bacterial culture group and the negative bacterial culture group had statistically significant differences in gender, age, body mass index (BMI), amylase, white blood cell count and the two groups of patients were comparable. A total of 156 patients were included in the study and pathogenic bacteria were cultured in the pancreatic juice of 64 patients (41.03%) and 94 strains of bacteria were found (Gram-positive bacteria, 38.30%; Gram-negative bacteria, 58.51%; fungi, 3.19%). A history of ERCP and early pancreatic necrosis were independent influencing factors of positive pancreatic juice culture. The incidence of complications, APACHE II, and inflammatory factor levels of patients with positive pancreatic juice bacterial culture were significantly higher than those of negative pancreatic juice bacterial culture (P<0.05). Multivariate regression and the ROC curve of pancreatic infection showed that positive pancreatic and Balthazar CT score >7 on admission were independent risk factors of pancreatic. The area under the ROC curve of patients with later pancreatic infection was 0.863 [95% confidence interval (CI): 0.769-0.957], specificity was 65.30%, sensitivity was 90.50%, and the Youden index was 0.603. Conclusions: Bacterial culturing of pancreatic juice provides evidence of infection in the early stage of AP, which has certain significance for the anti-infective therapy of AP.

Summary of the evidence of best practices for the prevention and treatment of embolism syndrome after TACE in primary liver cancer.

Objective: This study aims to retrieve, evaluate, and summarize domestic and foreign evidence on the prevention and treatment of embolism syndrome following transcatheter arterial chemoembolization (TACE) for primary liver cancer and to provide an evidence-based foundation for clinical practice. Methods: Utilizing the "6S" model, we conducted a systematic search of UpToDate, BMJ Best Practice, domestic and foreign guidelines, and related databases on the prevention and treatment of embolism syndrome following TACE for primary liver cancer. This search included clinical decision-making, guidelines, systematic reviews, evidence summaries, randomized controlled trials, and expert consensus. The search time frame extended from January 1, 2013 to May 1, 2023. Evidence was synthesized after an independent review of the included studies by two investigators. Results: A total of 11 articles were included in the analysis, comprising one clinical decision-making article, three clinical guidelines, six expert consensus articles, and one randomized controlled trial. We summarized 31 pieces of evidence across three categories: preoperative preparation, intraoperative interventions, and postoperative symptom management. Conclusion: This study presents a comprehensive summary of the best available evidence on the prevention and treatment of embolism syndrome following TACE for primary liver cancer. These findings can serve as a valuable reference for clinical practitioners, enabling nurses to deliver individualized care based on the symptoms and specific needs of liver cancer patients. Systematic review registration: http://ebn.nursing.fudan.edu.cn, identifier ES20232398.

Early endoscopic transpapillary drainage through the minor papilla in the treatment of acute pancreatitis.

Background: To explore the feasibility, safety, and efficacy of endoscopic transpapillary drainage through the minor papilla in the treatment of acute pancreatitis (AP). Methods: We retrospectively evaluated the safety and efficacy of endoscopic transpapillary drainage via the minor papilla among AP patients who were treated in our hospital from September 2018 to March 2020. Results: The present study included 18 patients (12 males and 6 females). All patients successfully received endoscopic transpapillary drainage via the minor papilla and were discharged upon recovery. No patient died, received ICU treatment, or had endoscopic operation-related complications. Two patients (11.11%) received additional abdominal paracentesis due to local complications. Fifteen patients (83.33%) resumed oral feeding within 3 days. The postoperative 24-hour leukocyte level, APACHE II score, serum amylase level, and lipase level significantly decreased compared with those at admission. The median hospitalization stay was 5 (3.75-9) days. The median hospitalization cost was 25,123.82 (22,942.50-43,874.68) RMB. The patients were followed up at 6-24 months, during which 4 patients (22.22%) had recurrence. Two patients had recurrence after pancreatic duct removal and other 2 patients in the period of carrying ducts. Conclusions: Early endoscopic transpapillary drainage via the minor papilla in cases of difficult cannulation or stenting via the major papilla is safe and effective in the treatment of AP, and is worthy of further popularization.

The comparison of different drip cholangiography: a randomised trial.

BACKGROUND: This study investigated the advantages and disadvantages of contrast media administration by gravity drip and manual push injection during cholangiography. METHODS: A total of 100 patients who presented to the Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, for a cholangiography between June 2019 to June 2020 were enrolled in this study. Patients were randomly divided into 2 treatment groups. One group of patients with manual injection of contrast (the N group, n=50), received the contrast agent via the traditional manual injection method whereby the doctor injects 50 mL of prepared contrast agent into the right side of the patient while continuously observing the effects on the bile duct. The other group of patients with gravity drip administration of contrast media (the O group, n=50), received the contrast agent via gravity drip at a rate of 80 drops per minute, and both clinicians and radiologists monitored the entire cholangiography process from a safe distance. Patients were followed up and angiographic satisfaction was assessed after two weeks. RESULTS: All 100 patients completed cholangiography without allergic reaction to the contrast medium. In the traditional injection group (N group), nine patients experienced upper abdominal discomfort with nausea, abdominal pain, chills, high fever, and other symptoms, and residual gallstones were observed in 12 patients. In patients in the gravity drip group (O group), four patients felt upper abdominal discomfort accompanied by nausea, abdominal pain, chills, high fever, and other symptoms, with residual gallstones detected in six patients. CONCLUSIONS: Patients who underwent gravity drip cholangiography had significantly reduced adverse reactions compared to patients who underwent traditional manual infusion cholangiography. Furthermore, gravity drip cholangiography resulted in clearer images and reduced X-ray exposure for medical staff. Thus, increased implementation of gravity drip cholangiography in the clinical setting should be considered. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800018202.

CX3CL1 Recruits NK Cells Into the Central Nervous System and Aggravates Brain Injury of Mice Caused by Angiostrongylus cantonensis Infection.

Background: Angiostrongylus cantonensis (A. cantonensis), is a food-borne zoonotic parasite that can cause central nervous system (CNS) injury characterized by eosinophilic meningitis. However, the pathogenesis of angiostrongylosis remains elusive. Natural killer cells (NK cells) are unique innate lymphocytes important in early defense against pathogens. The aim of this study was to investigate the role of NK cells in A. cantonensis infection and to elucidate the key factors that recruit NK cells into the CNS. Methods: Mouse model of A. cantonensis infection was established by intragastric administration of third-stage larvae. The expression of cytokines and chemokines at gene and protein levels was analyzed by qRT-PCR and ELISA. Distribution of NK cells was observed by immunohistochemistry and flow cytometry. NK cell-mediated cytotoxicity against YAC-1 cells was detected by LDH release assay. The ability of NK cells to secrete cytokines was determined by intracellular flow cytometry and ELISA. Depletion and adoptive transfer of NK cells in vivo was induced by tail vein injection of anti-asialo GM1 rabbit serum and purified splenic NK cells, respectively. CX3CL1 neutralization experiment was performed by intraperitoneal injection of anti-CX3CL1 rat IgG. Results: The infiltration of NK cells in the CNS of A. cantonensis-infected mice was observed from 14 dpi and reached the peak on 18 and 22 dpi. Compared with uninfected splenic NK cells, the CNS-infiltrated NK cells of infected mice showed enhanced cytotoxicity and increased IFN-γ and TNF-α production ability. Depletion of NK cells alleviated brain injury, whereas adoptive transfer of NK cells exacerbated brain damage in A. cantonensis-infected mice. The expression of CX3CL1 in the brain tissue and its receptor CX3CR1 on the CNS-infiltrated NK cells were both elevated after A. cantonensis infection. CX3CL1 neutralization reduced the percentage and absolute number of the CNS-infiltrated NK cells and relieved brain damage caused by A. cantonensis infection. Conclusions: Our results demonstrate that the up-regulated CX3CL1 in the brain tissue recruits NK cells into the CNS and aggravates brain damage caused by A. cantonensis infection. The findings improve the understanding of the pathogenesis of angiostrongyliasis and expand the therapeutic intervention in CNS disease.