Objective:To summarize the clinical characteristics of patients with acute pancreatitis (AP) in plateau areas, and screen potential biomarkers for the pathogenesis of AP at high altitudes by metabolomics.Methods:A total of 42 patients with AP admitted to the Department of Gastroenterology in Lhasa People's Hospital from December 2023 to May 2024 were prospectively enrolled (AP group), and 33 healthy controls (Control group) were included during the same period. Demographic and clinical data were collected, and serum non-targeted metabolomics was performed based on ultra-performance liquid chromatography-mass spectrometry techniques. The serum metabolites map was evaluated by using principal component analysis, and a regression model with orthogonal partial least squares-discriminant analysis (OPLS-DA) was constructed to evaluate the explanatory power ( R2) and predictive power ( Q2) of these metabolites. The OPLS-DA-based dimensionality reduction was applied to compute variable importance in projection (VIP), while fold change (FC) values were used to assess the difference of metabolites between groups. A bidirectional clustering heat map was generated for samples and differential metabolites to evaluate sample similarity within groups. Additionally, a volcano plot was created to visualize differential metabolites, and the top five up-regulated and down-regulated metabolites distinguishing AP from healthy controls were selected. The receiver operating characteristic curve (ROC) was drawn, and the area under the curve (AUC), sensitivity and specificity based on ROC analysis were calculated to evaluate the differential power of differential metabolites. Results:The majority of participants were Tibetans in both the AP group (37 cases, 88.1%) and the control group (27 cases, 81.8%). The average age of AP patients was (50.45±17.85) years old, and the male to female ratio was 1.1∶1.0. The leading etiology was biliary disease (33 cases, 78.6%), and most patients encountered moderately severe disease (26 cases, 61.9%). The incidence of local complications was 83.3%, mainly thoracoabdominal effusion and peripancreatic effusion (30 cases, 71.4%). The incidence of systemic complications was 59.5%, mainly systemic inflammatory response syndrome (22 cases, 52.4%) and respiratory failure (15 cases, 35.7%). Principal component analysis showed significant differences in serum metabolites between groups. OPLS-DA showed that these metabolites effectively distinguished AP patients from healthy controls: R2=0.992 and Q2=0.913 in the positive ion mode, R2=0.983 and Q2=0.914 in the negative ion mode. There were 450 up-regulated and 366 down-regulated differential metabolites in AP group, respectively. Among them, gamma-glutamylleucine, cortisone, 4(15)-Copaen-11-ol, mytiloxanthin, and indole-3-glycol aldehyde were the top five up-regulated metabolites, while N-Acetyltryptophan, kynurenic acid, deoxyuridine monophosphate, pseudouridine, and farnesyl acetate were the top five down-regulated metabolites. ROC analysis of these markers showed that all AUC values were >0.8, with all P values <0.001, with both sensitivity and specificity exceeding 80%. Among them, N-Acetyltryptophan and farnesyl acetate possessed the best differential performance. Conclusions:Biliary causes are most frequent among AP patients in plateau area. The disease severity is mainly moderately severe, accompanied by high incidences of local and systemic complications. Some amino acids and prenol lipids could significantly distinguish AP patients from healthy controls, and might be involved in the pathogenesis of AP at high altitudes.

Objective:To summarize the clinical characteristics of patients with acute pancreatitis (AP) in plateau areas, and screen potential biomarkers for the pathogenesis of AP at high altitudes by metabolomics.Methods:A total of 42 patients with AP admitted to the Department of Gastroenterology in Lhasa People's Hospital from December 2023 to May 2024 were prospectively enrolled (AP group), and 33 healthy controls (Control group) were included during the same period. Demographic and clinical data were collected, and serum non-targeted metabolomics was performed based on ultra-performance liquid chromatography-mass spectrometry techniques. The serum metabolites map was evaluated by using principal component analysis, and a regression model with orthogonal partial least squares-discriminant analysis (OPLS-DA) was constructed to evaluate the explanatory power ( R2) and predictive power ( Q2) of these metabolites. The OPLS-DA-based dimensionality reduction was applied to compute variable importance in projection (VIP), while fold change (FC) values were used to assess the difference of metabolites between groups. A bidirectional clustering heat map was generated for samples and differential metabolites to evaluate sample similarity within groups. Additionally, a volcano plot was created to visualize differential metabolites, and the top five up-regulated and down-regulated metabolites distinguishing AP from healthy controls were selected. The receiver operating characteristic curve (ROC) was drawn, and the area under the curve (AUC), sensitivity and specificity based on ROC analysis were calculated to evaluate the differential power of differential metabolites. Results:The majority of participants were Tibetans in both the AP group (37 cases, 88.1%) and the control group (27 cases, 81.8%). The average age of AP patients was (50.45±17.85) years old, and the male to female ratio was 1.1∶1.0. The leading etiology was biliary disease (33 cases, 78.6%), and most patients encountered moderately severe disease (26 cases, 61.9%). The incidence of local complications was 83.3%, mainly thoracoabdominal effusion and peripancreatic effusion (30 cases, 71.4%). The incidence of systemic complications was 59.5%, mainly systemic inflammatory response syndrome (22 cases, 52.4%) and respiratory failure (15 cases, 35.7%). Principal component analysis showed significant differences in serum metabolites between groups. OPLS-DA showed that these metabolites effectively distinguished AP patients from healthy controls: R2=0.992 and Q2=0.913 in the positive ion mode, R2=0.983 and Q2=0.914 in the negative ion mode. There were 450 up-regulated and 366 down-regulated differential metabolites in AP group, respectively. Among them, gamma-glutamylleucine, cortisone, 4(15)-Copaen-11-ol, mytiloxanthin, and indole-3-glycol aldehyde were the top five up-regulated metabolites, while N-Acetyltryptophan, kynurenic acid, deoxyuridine monophosphate, pseudouridine, and farnesyl acetate were the top five down-regulated metabolites. ROC analysis of these markers showed that all AUC values were >0.8, with all P values <0.001, with both sensitivity and specificity exceeding 80%. Among them, N-Acetyltryptophan and farnesyl acetate possessed the best differential performance. Conclusions:Biliary causes are most frequent among AP patients in plateau area. The disease severity is mainly moderately severe, accompanied by high incidences of local and systemic complications. Some amino acids and prenol lipids could significantly distinguish AP patients from healthy controls, and might be involved in the pathogenesis of AP at high altitudes.