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Acute pancreatitis is a common indication for hospital admission, increasing in incidence, including in children, pregnancy and the elderly. Moderately severe acute pancreatitis with fluid and/or necrotic collections causes substantial morbidity, and severe disease with persistent organ failure causes significant mortality. The diagnosis requires two of upper abdominal pain, amylase/lipase ≥ 3 ×upper limit of normal, and/or cross-sectional imaging findings. Gallstones and ethanol predominate while hypertriglyceridaemia and drugs are notable among many causes. Serum triglycerides, full blood count, renal and liver function tests, glucose, calcium, transabdominal ultrasound, and chest imaging are indicated, with abdominal cross-sectional imaging if there is diagnostic uncertainty. Subsequent imaging is undertaken to detect complications, for example, if C-reactive protein exceeds 150 mg/L, or rarer aetiologies. Pancreatic intracellular calcium overload, mitochondrial impairment, and inflammatory responses are critical in pathogenesis, targeted in current treatment trials, which are crucially important as there is no internationally licenced drug to treat acute pancreatitis and prevent complications. Initial priorities are intravenous fluid resuscitation, analgesia, and enteral nutrition, and when necessary, critical care and organ support, parenteral nutrition, antibiotics, pancreatic exocrine and endocrine replacement therapy; all may have adverse effects. Patients with local complications should be referred to specialist tertiary centres to guide further management, which may include drainage and/or necrosectomy. The impact of acute pancreatitis can be devastating, so prevention or reduction of the risk of recurrence and progression to chronic pancreatitis with an increased risk of pancreas cancer requires proactive management that should be long term for some patients.

Untargeted metabolomic analysis using mass spectrometry provides comprehensive metabolic profiling, but its medical application faces challenges of complex data processing, high inter-batch variability, and unidentified metabolites. Here, we present DeepMSProfiler, an explainable deep-learning-based method, enabling end-to-end analysis on raw metabolic signals with output of high accuracy and reliability. Using cross-hospital 859 human serum samples from lung adenocarcinoma, benign lung nodules, and healthy individuals, DeepMSProfiler successfully differentiates the metabolomic profiles of different groups (AUC 0.99) and detects early-stage lung adenocarcinoma (accuracy 0.961). Model flow and ablation experiments demonstrate that DeepMSProfiler overcomes inter-hospital variability and effects of unknown metabolites signals. Our ensemble strategy removes background-category phenomena in multi-classification deep-learning models, and the novel interpretability enables direct access to disease-related metabolite-protein networks. Further applying to lipid metabolomic data unveils correlations of important metabolites and proteins. Overall, DeepMSProfiler offers a straightforward and reliable method for disease diagnosis and mechanism discovery, enhancing its broad applicability. Untargeted metabolomic analysis provides comprehensive metabolic profiling but faces challenges in medical application. Here, the authors present an explainable deep learning method for end-to-end analysis on raw metabolic signals to differentiate metabolomic profiles of cancers with high accuracy.

The purpose of this study is to analyze the motion status of swimmers during their gliding stage using a numerical simulation method. This simulation strategy is conducted by solving the 3D incompressible Navier-Stokes equations using the Realizable k-ε turbulence closure equations in combination with the Six Degrees of Freedom (6-DOF) method. The uneven mass distribution of a swimmer and the roughness of the surface of the body are taken into consideration. The hydrodynamic characteristics and movement characteristics of the swimmers at different launch speeds were analyzed. The calculated results suggest that an optimal instant for starting propulsive movement is when the velocity of the swimmer decreases by 1.75 m/s to 2.0 m/s from an initial horizontal velocity of 3.1 m/s to 3.5 m/s.

An alkaline lipase strain of Pseudomonas aeruginosa HFE733 was isolated from soil samples of domestic waste. The alkaline lipase from P. aeruginosa HFE733 was purified and characterized. The enzyme was purified 9.97-fold by means of ammonium sulphate precipitation, Sephadex G-25 and diethylaminoethyl (DEAE) cellulose chromatography. Purified alkaline lipase protein was analyzed by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), the molecular mass was 51.0 kDa. The enzyme exhibited maximum activity at 40 °C and pH 8.5. The enzyme is stable at pH 7.0-8.5. It was remarkably activated by some metal ions and chemical reagents, such as Fe 3+ , Al 3+ , β-mercaptoethanol, cysteine, DL-dithiothreitol (DTT), Tween 80 and Triton X-100, but suppressed by sodium dodecyl sulfate (SDS) at 10 mmol/L. The P. aeruginosa HFE733 strain and lipase exhibited remarkable potential for biodegradation of oil and organics (measured as chemical oxygen demand (COD)). We demonstrated that it can be used for biodegradation of food wastewater from restaurants.

Background: Pain management is an important priority in the treatment of acute pancreatitis (AP). Current evidence and guideline recommendations are inconsistent on the most effective analgesic protocol. This systematic review and meta-analysis of randomised controlled trials (RCTs) aimed to compare the safety and efficacy of analgesics for pain relief in AP. Methods: A literature search was performed to identify all RCTs assessing analgesics in patients with AP. The primary outcome was the number of participants who needed rescue analgesia. Study quality was assessed using Jadad score. Pooled odds ratios (ORs) or weighted mean differences (WMDs) with 95% confidence intervals (CI) were analysed using a random-effects model. Results: Twelve studies comprising 699 patients with AP (83% mild AP) were analysed. The tested analgesics significantly decreased the need for rescue analgesia (3 studies, OR.36, 95% CI 0.21 to 0.60) vs. placebo or conventional treatment. The analgesics also improved the pain score [Visual Analogue Scale (Δ-VAS)] at 24 h (WMD 18.46, 0.84 to 36.07) and by the 3rd to 7th days (WMD 11.57, 0.87 to 22.28). Opioids vs. non-opioids were associated with a decrease in the need for rescue analgesia (6 studies, OR 0.25, 95% CI 0.07 to 0.86, p = 0.03) but without significance in pain score. In subgroup analyses, opioids were similar to non-steroidal anti-inflammatory drugs (NSAIDs) regarding the primary outcome (4 studies, OR 0.56, 95% CI 0.24 to 1.32, p = 0.18). There were no significant differences in other clinical outcomes and rate of adverse events. Other studies, comparing epidural anaesthesia vs. patient-controlled analgesia and opioid (buprenorphine) vs. opioid (pethidine) did not show significant difference in primary outcome. Study quality issues significantly contributed to overall study heterogeneity. Conclusions: NSAIDs and opioids are equally effective in decreasing the need for rescue analgesia in patients with mild AP. The relative paucity of trials and high-quality data in this setting is notable and the optimal analgesic strategy for patients with moderately severe and severe AP still requires to be determined.

Background Intra-abdominal hypertension (IAH) in acute pancreatitis (AP) is associated with deterioration in organ function. This trial aimed to assess the efficacy of neostigmine for IAH in patients with AP. Methods In this single-center, randomized trial, consenting patients with IAH within 2 weeks of AP onset received conventional treatment for 24 h. Patients with sustained intra-abdominal pressure (IAP) ≥ 12 mmHg were randomized to receive intramuscular neostigmine (1 mg every 12 h increased to every 8 h or every 6 h, depending on response) or continue conventional treatment for 7 days. The primary outcome was the percent change of IAP at 24 h after randomization. Results A total of 80 patients were recruited to neostigmine ( n  = 40) or conventional treatment ( n  = 40). There was no significant difference in baseline parameters. The rate of decrease in IAP was significantly faster in the neostigmine group compared to the conventional group by 24 h (median with 25th–75th percentile: −18.7% [− 28.4 to − 4.7%] vs. − 5.4% [− 18.0% to 0], P  = 0.017). This effect was more pronounced in patients with baseline IAP ≥ 15 mmHg ( P  = 0.018). Per-protocol analysis confirmed these results ( P  = 0.03). Stool volume was consistently higher in the neostigmine group during the 7-day observational period (all P  < 0.05). Other secondary outcomes were not significantly different between neostigmine and conventional treatment groups. Conclusion Neostigmine reduced IAP and promoted defecation in patients with AP and IAH. These results warrant a larger, placebo-controlled, double-blind phase III trial. Trial registration Clinical Trial No: NCT02543658 (registered August /27, 2015).

Xuebijing Injection (XBJ), a plant-derived traditional Chinese medicine administered as an injection, is widely used in clinical practice to treat various acute critical illnesses including severe acute pancreatitis (SAP). The mechanisms by which XBJ alleviates SAP remain elusive. Active components of XBJ were identified using UPLC-QTOF/MS. A mouse SAP model was established by intraperitoneal injections of cerulein (50 μg/kg/h × 7) followed by lipopolysaccharide (10 mg/kg). XBJ of 2.5, 5, and 10 mL/kg was co-administered twice after induction of SAP. The protective effects of XBJ on pancreatic acinar cells were further investigated in vitro. An integrated analysis of transcriptomic data from human and mouse blood, as well as mouse lung, combined with network pharmacology were employed to delineate the therapeutic mechanisms of XBJ on SAP, followed by pancreatic immunoblotting and proteomics validation. Component analysis revealed 9 active ingredients of XBJ. XBJ at 10 mL/kg had the best effect and consistently decreased pancreatic, lung, and circulatory pro-inflammatory indices. XBJ dose-dependently reduced necrotic cell death activation. Transcriptomics, proteomics and network pharmacology analyses identified 14 key targets, with IL-17-related signaling pathways being the most significant. Experimental validation further confirmed that XBJ significantly reduced serum levels of key IL-17-related inflammatory cytokines (such as IL-17, IL-1β, IL-6, and TNF-α) and downregulated the mRNA expression of related inflammatory factors in pancreatic tissue. Virtual docking and surface plasmon resonance demonstrate that hydroxysafflor yellow A had the highest binding affinity with MMP-9, MAPK14, and LCN2. Crucially, subsequent pancreatic immunoblotting and proteomics analyses did not confirm significant direct modulation of these targets at the protein level within pancreatic tissue. XBJ attenuates SAP severity by quelling pro-inflammatory mediators, an effect chiefly attributed to modulating systemic IL-17-related signaling rather than direct pancreatic intervention.

In the original article Fig. 3

Although severe abdominal pain is the main symptom of acute pancreatitis, its mechanisms are poorly understood. An emerging body of literature evidence indicates that neurogenic inflammation might play a major role in modulating the perception of pain from the pancreas. Neurogenic inflammation is the result of a crosstalk between injured pancreatic tissue and activated neurons, which leads to an auto-amplification loop between inflammation and pain during the progression of acute pancreatitis. In this review, we summarize recent findings on the role of neuropeptides, ion channels, and the endocannabinoid system in acute pancreatitis-related pain. We also highlight potential therapeutic strategies that could be applied for managing severe pain in this disease.

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine implicated in the pathogenesis of inflammation and cancer. It is produced by various cells and circulating MIF has been identified as a biomarker for a range of diseases. Extracellular MIF mainly binds to the cluster of differentiation 74 (CD74)/CD44 to activate downstream signaling pathways. These in turn activate immune responses, enhance inflammation and can promote cancer cell proliferation and invasion. Extracellular MIF also binds to the C-X-C chemokine receptors cooperating with or without CD74 to activate chemokine response. Intracellular MIF is involved in Toll-like receptor and inflammasome-mediated inflammatory response. Pharmacological inhibition of MIF has been shown to hold great promise in treating inflammatory diseases and cancer, including small molecule MIF inhibitors targeting the tautomerase active site of MIF and antibodies that neutralize MIF. In the current review, we discuss the role of MIF signaling pathways in inflammation and cancer and summarize the recent advances of the role of MIF in experimental and clinical exocrine pancreatic diseases. We expect to provide insights into clinical translation of MIF antagonism as a strategy for treating acute pancreatitis and pancreatic cancer.