Postoperative adjuvant immunotherapy and molecular targeted therapy for patients of hepatocellular carcinoma with portal vein tumor thrombus after hepatectomy: a propensity score matching study.

Background: Portal vein tumor thrombus (PVTT) is a major risk factor of recurrence of hepatocellular carcinoma (HCC) after hepatectomy. Whether postoperative adjuvant immunotherapy and molecular targeted therapy (I-O and MTT) is effective in reducing the risk of recurrence of HCC with minimal portal invasion after hepatectomy and improving prognosis is unknown. Methods: We collected the data of HCC with Vp1 or Vp2 PVTT patients who underwent hepatectomy at our center between January 2019 and June 2022 from the hospital database. We utilized propensity score matching (PSM) to establish a 1:1 match between the postoperative group treated with I-O and MTT and the postoperative group without I-O and MTT. To compare the recurrence-free survival (RFS) and overall survival (OS) between the two groups, we employed the Kaplan-Meier method. Additionally, we conducted Cox regression analysis to identify the prognostic factors that influence patient prognosis. To account for different high-risk factors, subgroup analyses were carried out. Results: Among the 189 patients included in the study, 42 patients received postoperative adjuvant I-O and MTT. After PSM, the 1, 2-years RFS were 59.2%, 21.3% respectively in the I-O and MTT group and 40.8%, 9.6% respectively in the non-I-O and MTT group. The median RFS was 13.2 months for the I-O and MTT group better than 7.0 months for the non-I-O and MTT group (P = 0.028). 1, 2-years OS were 89.8%, 65.8% respectively in the I-O and MTT group and 42.4%, 27.7% respectively in the non-I-O and MTT group. The median OS was 23.5 months for the I-O and MTT group better than 17.2 months for the non-I-O and MTT group (P = 0.027). Multivariate analysis showed that postoperative adjuvant I-O and MTT was a prognostic protective factor associated with OS and RFS. The most frequent AE observed in this study was pruritus, and rare AEs included decreased platelet, hypothyroidism, proteinuria, myocarditis and hypoadrenocorticism. The incidence of GRADE ≥3 AE with no deaths recorded. Conclusion: The study suggested that postoperative adjuvant I-O and MTT strategy was beneficial to improve the prognosis of HCC patients with PVTT patients, while the therapy was safe and reliable.

TGM1/3-mediated transamidation of Exo70 promotes tumor metastasis upon LKB1 inactivation.

Exo70, a key exocyst complex component, is crucial for cell motility and extracellular matrix (ECM) remodeling in cancer metastasis. Despite its potential as a drug target, Exo70's post-translational modifications (PTMs) are poorly characterized. Here, we report that Exo70 is transamidated on Gln5 with Lys56 of cystatin A by transglutaminases TGM1 and TGM3, promoting tumor metastasis. This modification enhances Exo70's association with other exocyst subunits, essential for secreting matrix metalloproteinases, forming invadopodia, and delivering integrins to the leading edge. Tumor suppressor liver kinase B1 (LKB1), whose inactivation accelerates metastasis, phosphorylates TGM1 and TGM3 at Thr386 and Thr282, respectively, to inhibit their interaction with Exo70 and the following transamidation. Cantharidin, a US Food and Drug Administration (FDA)-approved drug, inhibits Exo70 transamidation to restrain tumor cell migration and invasion. Together, our findings highlight Exo70 transamidation as a key molecular mechanism and target and propose cantharidin as a therapeutic strategy with direct clinical translational value for metastatic cancers, especially those with LKB1 loss.

N6-methyladenosine RNA modification regulates photoperiod sensitivity in cotton.

The methylation of N6-methyladenosine (m6A) involves writers, erasers, and readers, acting synergistically in posttranscriptional regulation. These processes influence various biological processes, including plant floral transition. However, the specific role of m6A modifications in photoperiod sensitivity in cotton (Gossypium hirsutum) remains obscure. To elucidate this, in this study, we conducted transcriptome-wide m6A sequencing during critical flowering transition stages in the photoperiod-sensitive wild G. hirsutum var. yucatanense (yucatanense) and the photoperiod-insensitive cultivated cotton G. hirsutum acc. TM-1 (TM-1). Our results revealed significant variations in m6A methylation of 2 cotton varieties, with yucatanense exhibiting elevated m6A modification levels compared with TM-1 under long-day conditions. Notably, distinct m6A peaks between TM-1 and yucatanense correlated significantly with photoperiod sensitivity. Moreover, our study highlighted the role of the demethylase G. hirsutum ALKB homolog 5 (GhALKBH5) in modulating m6A modification levels. Silencing GhALKBH5 led to a decreased mRNA level of key photoperiodic flowering genes (GhADO3, GhAGL24, and GhFT1), resulting in delayed bud emergence and flowering. Reverse transcription quantitative PCR analyses confirmed that silencing GhADO3 and GhAGL24 significantly downregulated the expression of the floral integrator GhFT1. Collectively, our findings unveiled a transcriptional regulatory mechanism in which GhALKBH5-mediated m6A demethylation of crucial photoperiodic flowering transcripts modulated photoperiod sensitivity in cotton.

Risk factors of negative diagnosis of MRCP in acute biliary pancreatitis patients with choledocholithiasis.

BACKGROUND: Assessment of the presence of choledocholithiasis is crucial among acute biliary pancreatitis (ABP). Magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasonography (EUS) are widely used to identify the gallstones of common bile duct (CBD). EUS provides better diagnostic accuracy and sensitivity than MRCP but carries a certain risk due to sedation. We investigated the risk factors of negative diagnosis of MRCP in ABP patients with choledocholithiasis for better selection of MRCP or EUS. METHODS: A total of 2321 ABP patients were retrospectively included in this study. Based on the exclusion criteria, 337 ABP patients with negative MRCP results were ultimately included. Among these patients, 75 patients had positive EUS findings. Univariate and multivariate logistic regression models were used to screen the risk factors of negative diagnosis of MRCP in ABP patients with choledocholithiasis. RESULTS: Patients with positive EUS findings were older (62.0 vs. 55.0) and had higher rate of cholecystectomy history (18.7% vs. 7.3%) than those with negative EUS findings. The result of univariate logistic regression showed that the history of cholecystectomy, age and sex were potential risk factors (all p < 0.05). Then after adjusting the other potential risk factors (Direct bilirubin (DBIL), alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP)), a history of cholecystectomy (OR = 2.859 [1.312,6.23]), older age (1.03 [1.009,1.052]) and male (2.016 [1.152,3.528]) were independent risk factors of negative diagnosis of MRCP in ABP patients with choledocholithiasis. CONCLUSIONS: The history of cholecystectomy, older age and male are independently associated with an increased risk of negative diagnosis of MRCP in ABP patients with choledocholithiasis. We suggest that patients with these risk factors should undergo EUS first, rather than MRCP.

Macrophage Tim-3 maintains intestinal homeostasis in DSS-induced colitis by suppressing neutrophil necroptosis.

T-cell immunoglobulin domain and mucin domain-3 (Tim-3) is a versatile immunomodulator that protects against intestinal inflammation. Necroptosis is a type of cell death that regulates intestinal homeostasis and inflammation. The mechanism(s) underlying the protective role of macrophage Tim-3 in intestinal inflammation is unclear; thus, we investigated whether specific Tim-3 knockdown in macrophages drives intestinal inflammation via necroptosis. Tim-3 protein and mRNA expression were assessed via double immunofluorescence staining and single-cell RNA sequencing (sc-RNA seq), respectively, in the colonic tissues of patients with inflammatory bowel disease (IBD) and healthy controls. Macrophage-specific Tim3-knockout (Tim-3M-KO) mice were generated to explore the function and mechanism of Tim-3 in dextran sodium sulfate (DSS)-induced colitis. Necroptosis was blocked by pharmacological inhibitors of receptor-interacting protein kinase (RIP)1, RIP3, and reactive oxygen species (ROS). Additionally, in vitro experiments were performed to assess the mechanisms of neutrophil necroptosis induced by Tim-3 knockdown macrophages. Although Tim-3 is relatively inactive in macrophages during colon homeostasis, it is highly active during colitis. Compared to those in controls, Tim-3M-KO mice showed increased susceptibility to colitis, higher colitis scores, and increased pro-inflammatory mediator expression. Following the administration of RIP1/RIP3 or ROS inhibitors, a significant reduction in intestinal inflammation symptoms was observed in DSS-treated Tim-3M-KO mice. Further analysis indicated the TLR4/NF-κB pathway in Tim-3 knockdown macrophages mediates the TNF-α-induced necroptosis pathway in neutrophils. Macrophage Tim-3 regulates neutrophil necroptosis via intracellular ROS signaling. Tim-3 knockdown macrophages can recruit neutrophils and induce neutrophil necroptosis, thereby damaging the intestinal mucosal barrier and triggering a vicious cycle in the development of colitis. Our results demonstrate a protective role of macrophage Tim-3 in maintaining gut homeostasis by inhibiting neutrophil necroptosis and provide novel insights into the pathogenesis of IBD.

Etiological Changes and Prognosis of Hospitalized Patients with Acute Pancreatitis Over a 15-Year Period.

BACKGROUND: The worldwide incidence of acute pancreatitis (AP) is increasing, but the dominant etiology of AP may vary by country. Mixed etiologies are involved in the increase in the number of AP patients. AIMS: This study was to analyze the etiological changes and prognosis of AP patients and explore the prognosis of AP patients with mixed etiologies. METHODS: Using a retrospective analysis method, AP patients hospitalized from January 2007 to December 2021 were selected from a pancreatic center in Nanchang, China. Trends in the main etiologies were analyzed, and the severity and prognosis of different etiologies were compared. RESULTS: A total of 10,071 patients were included. Cholelithiasis (56.0%), hyperlipidemia (25.3%), and alcohol (6.5%) were the top three etiologies. The proportion of acute biliary pancreatitis (ABP) showed a decreasing trend, while the proportion of hypertriglyceridemic pancreatitis (HTGP) and alcoholic AP showed an increasing trend (all ptrend < 0.001). The incidence of organ failure and necrotizing pancreatitis was higher in patients with HTGP than in those with AP induced by other etiologies (all p < 0.05). There was no statistically significant difference in mortality among patients with different etiologies. Patients with AP due to a mixed hypertriglyceridemia-alcoholic etiology had higher ICU admission rates and were more severe than those with AP induced by other mixed etiologies. CONCLUSION: In the past 15 years, the proportion of ABP has trended downward, while those of HTGP and alcoholic AP have risen. Among patients with mixed etiologies, those with a mixed hypertriglyceridemia-alcoholic etiology had a worse prognosis.

Elevated CK-MB levels are associated with adverse clinical outcomes in acute pancreatitis: a propensity score-matched study.

Aim: Cardiac injury, reflected by the measured concentrations of chemicals released from injured cardiac muscle, is common in acute pancreatitis (AP). However, there is no adequate evidence assessing the impact of cardiac injury on AP-related outcomes. Creatine kinase-myocardial band (CK-MB) mainly exists in the myocardium. Therefore, we sought to evaluate the relationship between the increase in CK-MB and the adverse clinical outcomes of AP. Methods: This propensity score-matched study analyzed AP patients admitted to the Department of Gastroenterology in the First Affiliated Hospital of Nanchang University from June 2017 to July 2022. Propensity score matching and multivariate logistic regression analysis were used to explore the relationship between CK-MB elevation and AP outcome variables. Results: A total of 5,944 patients were screened for eligibility, of whom 4,802 were ultimately enrolled. Overall, 896 (18.66%) of AP patients had elevated (>24 U/ml) CK-MB levels, and 895 (99.89%) were paired with controls using propensity score matching. The propensity score-matched cohort analysis demonstrated that mortality (OR, 5.87; 95% CI, 3.89-8.84; P < 0.001), severe acute pancreatitis (SAP) (OR, 2.74; 95% CI, 2.23-3.35; P < 0.001), and infected necrotizing pancreatitis (INP) (OR, 3.40; 95% CI, 2.34-4.94; P < 0.001) were more frequent in the elevated CK-MB (>24 U/ml) group than in the normal CK-MB (≤ 24 U/ml) group. Using the multivariate logistic regression analysis, elevated CK-MB levels were independently associated with increased mortality (OR, 2.753, 95% CI, 2.095-3.617, P < 0.001), SAP incidence (OR, 2.223, CI, 1.870-2.643, P < 0.001), and INP incidence (OR, 1.913, 95% CI, 1.467-2.494, P < 0.001). CK-MB elevation was an independent risk factor for adverse clinical outcomes in AP patients. Conclusion: CK-MB elevation was significantly related to adverse outcomes in AP patients, which makes it a potentially useful laboratory parameter for predicting adverse clinical outcomes of AP.

The severity and infection of acute pancreatitis may increase the risk of bleeding in patients undergoing EUS-guided drainage and endoscopic necrosectomy: a large retrospective cohort.

BACKGROUND: There has been great progress in the use of endoscopic ultrasound (EUS)-guided drainage in acute pancreatitis patients using a novel lumen-apposing metal stent (LAMS) in the last decade, but some patients experience bleeding. Our research analyzed the preprocedural risk factors for bleeding. METHODS: From July 13, 2016 to June 23, 2021, we retrospectively analyzed all patients who received endoscopic drainage by the LAMS in our hospital. Univariate and multivariate statistical analyses were used to identify the independent risk factors. We plotted ROC curves based on the independent risk factors. RESULTS: A total of 205 patients were analyzed and 5 patients were excluded. A total of 200 patients were included in our research. Thirty (15%) patients presented with bleeding. In the multivariate analysis, computed tomography severity index score (CTSI) score [odds ratio (OR), 2.66; 95% CI: 1.31-5.38; P = 0.007], positive blood cultures [odds ratio (OR), 5.35; 95% CI: 1.31-21.9; P = 0.02], and Acute Physiology and Chronic Health Evaluation II (APACHE II) score [odds ratio (OR), 1.14; 95% CI: 1. 01-1.29; P = 0.045] were associated with bleeding. The area under the ROC curve of the combined predictive indicator was 0.79. CONCLUSION: Bleeding in endoscopic drainage by the LAMS is significantly associated with the CTSI score, positive blood cultures, and APACHE II score. This result could help clinicians make more appropriate choices.

Correlation between immune-related adverse events and long-term outcomes in pembrolizumab-treated patients with unresectable hepatocellular carcinoma: A retrospective study.

BACKGROUND: Although immune checkpoint inhibitor (ICI) therapy has improved the prognosis of unresectable hepatocellular carcinoma (HCC), it has also resulted in unique immune-related adverse events (irAEs). The relationship between irAE and treatment outcomes in ICI-treated unresectable HCC patients remains unknown. AIM: To elucidate the correlation between immune-related toxic effects and prognosis in patients with unresectable HCC treated with pembrolizumab. METHODS: From March 2019 to February 2021, a total of 190 unresectable HCC (Barcelona Clinic Liver Cancer C) patients receiving pembrolizumab treatment were retrospectively reviewed. Overall survival (OS) was the primary endpoint, while objective response rate (ORR), disease control rate (DCR), and time to progression (TTP) were secondary evaluation indexes. We assessed demographics, irAEs, and outcomes by retrospective review. RESULTS: One hundred and forty-three males and 47 females were included in the study. The ORR and DCR were 12.1% (23/190) and 52.1% (99/190), respectively. The median OS was 376 d [95% confidence interval (CI): 340-411 d] and the median TTP was 98 d (95%CI: 75-124 d). The overall incidence of treatment-related adverse events was 72.6% (138/190) and 10.0% of them were severe irAEs (grade ≥ 3). Child-Pugh B class, portal vein tumor thrombus, extrahepatic metastasis, and hypothyroidism were the independent risk factors for survival. Patients with hypothyroidism showed a longer OS [517 d (95%CI: 423-562) vs 431 d (95%CI: 412-485), P = 0.011] and TTP [125 d (95%CI: 89-154) vs 87 d (95%CI: 61-98), P = 0.004] than those without irAEs. CONCLUSION: Pembrolizumab-treated patients with unresectable HCC who experienced hypothyroidism have promising ORR and durable response. Hypothyroidism, an irAE, may be used as a clinical evaluation parameter of response to ICIs in unresectable HCC.

Serum triglyceride levels are associated with recurrence in patients with acute hypertriglyceridemic pancreatitis.

Aim: To analyze the clinical profile of patients with acute hypertriglyceridemic pancreatitis (HTGP) and explore risk factors for recurrence. Methods: A retrospective observational study was conducted in patients who experienced an attack of HTGP for the first time. Patients were followed until the recurrence of acute pancreatitis (AP) or 1 year. The detailed clinical profile was compared between patients with or without recurrence. Multivariate logistic regression analysis was conducted to explore independent risk factors for recurrence. Results: A total of 108 HTGP patients were included in this study with 73.1% being male, and the median age being 37 (interquartile range, IQR, 30.3-44.8) years. Recurrence occurred in 70 patients (64.8%). Compared with the nonrecurrent group, serum triglyceride (TG) levels before discharge [4.1 (2.8,6.3) mmol/L vs. 2.9 (2.2,4.2) mmol/L; p = 0.002], at 1 month [3.7 (2.3,9.7) mmol/L vs. 2.0 (1.4,2.7) mmol/L; p = 0.001], at 6 months [6.1 (3.1,13.1) mmol/L vs. 2.5 (1.1,3.5) mmol/L; p = 0.003] and 12 months [9.6 (3.5,20.0) mmol/L vs. 2.7 (1.6,5.5) mmol/L; p = 0.001] after discharge were higher in the recurrent group. Poor control of TG levels (TG > 3.1 mmol/l) at the 1-month follow-up after discharge and a high Charlson's Comorbidity Index score (≥ 2 points) increased the risk of recurrence of HTGP. Conclusion: High TG levels during follow-up and Charlson's Comorbidity Index score were independently associated with recurrence in patients with HTGP.

Lactulose regulates gut microbiota dysbiosis and promotes short-chain fatty acids production in acute pancreatitis patients with intestinal dysfunction.

BACKGROUND: Intestinal dysfunction is one of the common complications in the early stage of acute pancreatitis (AP), which often associates with bad outcome. Lactulose, as a prebiotic, has been widely used to improve gut health, yet its effect on AP is unclear. METHODS: This was a prospective, randomized trial of moderate severe AP patients complicated with intestinal dysfunction. A total of 73 participants were randomly assigned to receive either lactulose or Chinese herb rhubarb for 1 week. The primary efficacy endpoint was the recovery of intestinal function. The serum levels of inflammatory cytokines and gut barrier indexes were examined. The fecal samples from patients before and after treatment were collected. 16 S rRNA gene sequencing analysis was performed to explore the composition of gut microbiota and the amount of short-chain fatty acids (SCFAs) were detected by gas chromatography-mass spectrometry (GC-MS). RESULTS: The intestinal dysfunction was prominently improved after 7 days of treatment with either lactulose or rhubarb. The serum levels of cytokines and gut permeability index were decreased after treatment, with stronger down-regulated degree in lactulose group than rhubarb. The potential beneficial genus Bifidobacterium was enriched in lactulose group, while pathogenic bacteria including Escherichia-Shigella and Neisseria were abundant in rhubarb group. Of note, the level of SCFAs was remarkably increased after treatment, with higher amount in lactulose group than rhubarb group. CONCLUSIONS: Lactulose could not only restore intestinal function but also regulate gut microbiota and promote the production of SCFAs.

Eudragit-coated chitosan-tripterygium glycoside conjugate microspheres alleviate DSS-induced experimental colitis by inhibiting the TLR4/NF-κB signaling pathway.

OBJECTIVE: Tripterygium glycoside (TG) is a fat-soluble extract of Tripterygium wilfordii, with anti-inflammatory properties associated with TLR signaling pathways. This study constructed a targeted delivery system for experimental colitis, namely, eudragit (EuL)-coated chitosan (Ch)-TG conjugate microspheres (Ch-TG-MS/EuL), and evaluated its therapeutic efficacy and underlying mechanisms. METHODS: Ch-TG-MS was fabricated using emulsification cross-linking technique and then coated with EuL to create Ch-TG-MS/EuL. Drug release properties were assessed using a dialysis model. Additionally, the therapeutic benefits of Ch-TG-MS/EuL on colonic inflammation and its specific effect on TLR4/NF-κB signaling in intestinal mucosa were evaluated in vivo using a DSS-induced murine colitis model. RESULTS: The Ch-TG-MS/EuL microspheres appeared as yellow powders with a slightly enlarged shape, rough surface, and adhesions. The Ch-TG-MS/EuL formulations also exhibited high entrapment efficiency and drug loading rate. High-performance liquid chromatography revealed that Ch-TG-MS/EuL exhibited a less intense peak than free TG, confirming that the drug is contained within the formulation. Free TG displayed explosive release within the first 5 h of administration, while Ch-TG-MS/EuL prevented the pre-mature release of TG and exhibited controllable release up to 24 h. In vivo, noticeable amelioration of intestinal mucosal tissue destruction was achieved with Ch-TG-MS/EuL compared to free TG. Additionally, immunohistochemical and western blotting results revealed that Ch-TG-MS/EuL markedly down-regulated the expression of intestinal mucosal TLR4, MyD88, and NF-κB p65. Hence, Ch-TG-MS/EuL may ameliorate the colon inflammatory response by inhibiting the hyperactivation of TLR4/NF-κB signaling. CONCLUSION: Novel Ch-TG-MS/EuL preparation may represent a colonic delivery system for UC therapeutics by inhibiting TLR4/NF-κB hyperactivation. DATA AVAILABILITY: All experimental data supporting the conclusions of this study are available from the corresponding author on reasonable request.

A bibliometric analysis of inflammatory bowel disease and COVID-19 researches.

Background: Patients with inflammatory bowel disease (IBD) often require immunosuppressive therapy and are hence susceptible to various opportunistic viral and bacterial infections. In this regard, many studies on IBD and COVID-19 have been conducted. However, no bibliometric analysis has been performed. This study provides a general overview of IBD and COVID-19. Methods: Publications about IBD and COVID-19 from 2020 to 2022 were retrieved from the Web of Science Core Collection (WoSCC) database. Bibliometric analysis was performed using VOSviewer, CiteSpace, and HistCite. Results: A total of 396 publications were retrieved and considered in this study. The maximum number of publications were from the United States, Italy, and England, and the contributions of these countries were significant. Kappelman ranked first in article citations. The Icahn School of Medicine at Mount Sinai and Inflammatory Bowel Diseases were the most prolific affiliation and journal, respectively. The most influential research topics were "management", "impact", "vaccination", and "receptor". The following keywords represented research frontiers: "depression", "the quality of life of IBD patients", "infliximab", "COVID-19 vaccine", and "second vaccination". Conclusions: Over the past 3 years, most studies on IBD and COVID-19 have focused on clinical research. In particular, topics such as "depression", "the quality of life of IBD patients", "infliximab", "COVID-19 vaccine", and "second vaccination" were noted to have received much attention recently. Future research should focus on our understanding of the immune response to COVID-19 vaccination in biologically treated patients, the psychological impact of COVID-19, IBD management guidelines, and the long-term impact of COVID-19 in IBD patients. This study will provide researchers with a better understanding of research trends on IBD during COVID-19.

Effect of exogenous galectin-9, a natural TIM-3 ligand, on the severity of TNBS- and DSS-induced colitis in mice.

Inflammatory bowel disease (IBD) have a complex pathogenesis that is yet to be completely understood. However, a strong correlation between Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling and IBD has been observed. T-cell immunoglobulin and mucin domain-containing-3 (Tim-3) has been reported to regulate TLR4/NF-κB by interacting with Galectin-9 (Gal-9), and recombinant Gal-9 can activate Tim-3; however, its potential properties in IBD and the underlying mechanism remain unclear. This study aimed to determine how Gal-9 affects experimental colitis in mice. Dextran sodium sulfate (DSS) and 2,4,6-trinitrobenzene sulfonic acid (TNBS) were used to establish colitis in mice, and the severity of the illness was assessed based on body weight, colon length, and histology. Therefore, we explored the effects of Gal-9 treatment on colitis. Furthermore, we analyzed the effect of Gal-9 on the expression of Tim-3 and TLR4/NF-κB pathway in colonic tissues and the serum levels of interferon-gamma (IFN-γ), interleukin (IL)-1ß, and IL-6. Tim-3 expression in the colon was notably decreased in mice with TNBS-induced colitis, whereas TLR4/NF-kB expression was significantly increased. Intraperitoneal injection of Gal-9 dramatically decreased the disease activity index and attenuated the level of intestinal mucosal inflammation in TNBS-induced colitis mice (p < 0.05). Intraperitoneal administration of Gal-9 significantly increased Tim-3 expression in the colon and decreased the serum concentrations of IFN-γ, IL-1ß, and IL-6. Additionally, Gal-9 treatment significantly downregulated the expression of TLR4 signaling pathway-related proteins. In contrast, Gal-9 did not reduce the severity of DSS-induced colitis. In summary, exogenous Gal-9 increased Tim-3 expression, inhibited the TLR4/NF-κB pathway, and alleviated TNBS-induced colitis in mice but not DSS-induced colitis in mice, revealing its potential therapeutic ramifications for IBD.

Recurrence for patients with first episode of hypertriglyceridemia-induced acute pancreatitis: A prospective cohort study.

BACKGROUND: Data on recurrent hypertriglyceridemia-induced acute pancreatitis (HTG-AP) are scarce. OBJECTIVE: To investigate the incidence and risk factors for recurrence of HTG-AP, and the effect of triglyceride (TG) lowering drugs post index attack on recurrence. METHODS: This study was a prospective cohort study of adult patients with first episode of HTG-AP from December 2019 to February 2021 who were followed until recurrence or death, or February 2022. The cumulative incidence function and Fine and Gray's competing-risk model were applied to the analyses. RESULTS: A total of 317 patients were enrolled, and the 12-month and 18-month cumulative recurrence incidences were 8% and 22%, respectively. The cumulative recurrence incidence was 2 times higher in patients whose serum TG levels post index attack were ≥5.65 mmol/L (subdistribution hazard ratio [SHR], 2.00; 95% confidence interval [CI], 1.05-3.80; P = 0.034) compared to patients with TG <5.65 mmol/L. The recurrence rate was 3.3 times higher in patients whose glucose levels post index attack were ≥7.0 mmol/L (SHR, 3.31; 95% CI, 1.56-7.03; P = 0.002) than in patients with glucose <7.0 mmol/L). Compared to TG lowering drugs for less than 1 month post index attack, treatment for longer than 12 months decreased the incidence of recurrence by 75% (SHR, 0.25; 95% CI, 0.08-0.80; P = 0.019). CONCLUSIONS: The HTG-AP recurrence incidence is high and closely associated with high levels of TGs and glucose post index attack. Long-term TG lowering drugs treatment significantly decreases this recurrence.

Pancreatic necrosis volume for predicting readmission and reintervention in acute necrotizing pancreatitis.

PURPOSE: To determine the correlation between the pancreatic necrosis volume (PNV) and readmission as well as reintervention. METHOD: This was a retrospective cohort study that included necrotizing pancreatitis (NP) patients who were examined with contrast-enhanced computed tomography (CT) one week before discharge. The PNV was calculated manually based on the postprocessing workstation software. Multivariate logistic regression analysis was employed to determine the independent risk factors for readmission and reintervention. RESULTS: A total of 167 NP patients were included. Among them, 94 (56.3%) patients were readmitted after discharge, and 55 (32.9%) patients needed further invasive intervention. The median PNV of all patients was 376.6 (interquartile range (IQR), 129.3-820.5) cm3, and the PNV was significantly higher in patients needing readmission or reintervention. Multivariate analysis showed that PNV ≥ 620 cm3 (adjusted odds ratio (adjOR), 3.08; 95% confidence interval (CI), 1.47-6.43; P = 0.003) and modified computed tomography severity index (CTSI) score ≥ 7 points (adjOR, 6.36; 95% CI, 2.05-10.70; P = 0.001) were independently associated with readmission. Stent or drainage tube placement at discharge (adjOR, 2.94; 95% CI, 1.27-6.77; P = 0.011), PNV ≥ 620 cm3 (adjOR, 5.11; 95% CI, 2.19-11.95; P < 0.001), pancreatic parenchymal necrosis (adjOR, 3.37; 95% CI, 1.42-7.96; P = 0.006), and modified CTSI score ≥ 7 points (adjOR, 4.23; 95% CI, 1.46-12.27; P = 0.008) were independent risk factors for reintervention. CONCLUSIONS: The PNV is a useful tool for quantifying pancreatic necrosis and is strongly associated with readmission and reintervention. Additional prospective studies with larger sample sizes are needed to confirm these findings.

Dynamic Changes and Nomogram Prediction for Sinistral Portal Hypertension in Moderate and Severe Acute Pancreatitis.

Objectives: To investigate the dynamic changes in gastric varices in patients with acute pancreatitis (AP) and to develop a novel nomogram for the early prediction of sinistral portal hypertension (SPH). Methods: This was a retrospective, case-control study with an analysis of the quantitative, dynamic computed tomography imaging results of SPH in patients with moderate and severe AP with a long-term follow-up. Multivariate logistic regression analysis and nomogram were employed. Results: The SPH group (n = 94) and non-SPH group (n = 94) were matched. The dynamic changes showed an increasing trend in the diameter of gastric fundus, short gastric, gastric coronary, and gastroepiploic veins, which did not recover during the one-year follow-up. Multivariate analysis showed that male (adjusted odds ratio (adjOR), 8.71; 95% confidence interval (CI), 2.86-26.53; P < 0.001), body mass index ≥27.5 kg/m2 (adjOR, 5.49; 95% CI, 1.85-16.29; P = 0.002), prothrombin time ≥12.6 s (adjOR, 2.82; 95% CI, 1.11-7.17; P = 0.03), and the patency of splenic vein [stenosis (adjOR, 8.48; 95% CI, 2.13-33.71; P = 0.002), and occlusion (adjOR, 34.57; 95% CI, 10.87-110.00; P < 0.001)] were independently associated with the development of SPH. The nomogram incorporating these factors demonstrated good discrimination, calibration and clinical utility. The area under the curve was as high as 0.92 (95% CI, 0.87-0.95). Conclusion: The dynamic changes in varices in SPH are long-term and slowly progressing. Males and obese patients with abnormal splenic veins and coagulopathies are at high risk for developing SPH. A simple nomogram tool helps in the early, accurate prediction of SPH.

The Value of Serum Tumor Markers and Blood Inflammation Markers in Differentiating Pancreatic Serous Cystic Neoplasms and Pancreatic Mucinous Cystic Neoplasms.

Although many studies have emphasized the prognostic and diagnostic value of tumor markers and various inflammation-related markers, their clinical significance in differentiating benign and malignant pancreatic cystic neoplasms (PCNs) remains to be clarified. The present study explored the value of serum tumor markers and inflammation-related biomarkers in the differentiation of pancreatic serous cystic neoplasms (SCNs) and pancreatic mucinous cystic neoplasms (MCNs). A total of 79 patients with PCNs were included in this study, including 35 patients with SCNs and 44 patients with MCNs. Comparison of baseline data with preoperative results of serum tumor markers and associated inflammatory markers revealed significant differences in carbohydrate antigen 199 (CA199) and "lymphocyte × ALB" (LA) between the two groups (p = 0.0023, p = 0.0149, respectively). Univariate and multivariate regression analyses showed that an increase in CA199 and a decrease in LA were relevant risk factors for MCNs. Finally, the receiver operating characteristic (ROC) curve was generated, and the area under the ROC curve (AUC) was calculated to evaluate the prediction efficiency of each indicator. The results showed that CA199 and LA had good differential diagnostic efficacy for SCNs and MCNs. This is the first to report to demonstrate that LA can be used for the differential diagnosis of SNCs and MCNs.

A Novel Strategy for Transmural Stent Removal in Necrotizing Pancreatitis Undergoing Endoscopic Transmural Necrosectomy.

BACKGROUND: Although metal stents have been widely used in the endoscopic step-up approach for necrotizing pancreatitis, the exact timing of transmural stent removal has not been well studied. Here, we report a novel strategy for stent removal and compare it with the conventional strategy. MATERIALS AND METHODS: This retrospective, nested, case-control study analyzed all adult necrotizing pancreatitis patients who underwent endoscopic transmural necrosectomy (ETN). Clinical outcomes were compared between case group (a novel strategy in which the stents were removed during the last necrosectomy when the ETN endpoint was achieved) and 1:1 necrosis extent matched control group (the conventional strategy). RESULTS: Baseline characteristics was comparable between case group (n=37) and control group (n=37). Three (8.1%) patients in case group and 1 (2.7%) patient in control group needed additional ETN after stent removal (P>0.05). Nearly all patients (case: 97.3%; control: 94.6%) achieved clinical success. There was no difference in disease-related (case: 40.5%; control: 37.8%) or stent-related (case: 27.0%; control: 16.2%) complications. Case group had a trend of shorter length of stent placement (median: 20.0 vs. 29.5 d, P>0.05). CONCLUSIONS: The novel strategy of transmural stent removal during last necrosectomy might be feasible which needed further validation. Compared with the convention strategy, the novel strategy avoids one endoscopy procedure and should be considered in clinical practice.

Emerging Trends in Intestinal Knowledge Structure Associated With Acute Pancreatitis From 1981 to 2021: A Bibliometric Analysis.

OBJECTIVES: Bibliometric analysis has not comprehensively summarized studies of acute pancreatitis (AP)-associated intestinal diseases. This work aimed to evaluate cooperative networks of authors, countries, and institutions and explore the field's developing trends and hot topics. METHODS: Original articles and reviews of AP-associated intestinal diseases were obtained from the Web of Science Core Collection on October 11, 2021. VOSviewer and CiteSpace software were used to perform co-occurrence analyses for authors, countries, and institutions and detect the highest citation burst. RESULTS: A total of 1634 articles on the intestine associated with AP were identified. The United States, the University of Auckland, and Roland Andersson are the most influential country, research institute, and scholar, respectively. The World Journal of Gastroenterology (73 articles) has the highest number of publications, and Gastroenterology was the most co-cited journal. The top 5 key words are "acute pancreatitis," "bacterial translocation," "management," "gut," and "inflammatory bowel disease." We find that several emergent key words like "gut microbiota," "pathway," "gut barrier," "risk," and "oxidative stress" experienced a continuous and rapid development as new research directions. CONCLUSIONS: This bibliometric study summarizes current important perspectives and offers comprehensive guidance on the AP-associated intestinal diseases, which may help researchers choose the most appropriate research directions.