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Resumen Introducción: La pancreatitis aguda se observa con mayor frecuencia en la edad pediátrica. Actualmente existen guías de recomendaciones para su adecuado diagnóstico y tratamiento. El objetivo de este estudio fue evaluar el nivel de conocimiento de las recomendaciones internacionales sobre pancreatitis aguda de la North American Society for Pediatric Gastroenterology, Hepatology and Nutrition en un grupo de pediatras. Métodos: Estudio observacional, multicéntrico, mediante una encuesta aplicada a médicos pediatras y médicos pediatras en formación. Resultados: El 48.8% de los médicos tenían conocimiento de las guías para tratamiento de pancreatitis aguda en niños. El 72.4% conocían los criterios actuales para el diagnóstico de pancreatitis aguda. No hubo diferencias en la mayoría de las respuestas entre médicos pediatras y médicos pediatras en formación. Conclusiones: Aunque solo la mitad de los encuestados conocían la guía para el diagnóstico y el tratamiento de la pancreatitis aguda, cerca de tres cuartas partes utilizan adecuadamente los criterios para el diagnóstico. Existe adecuado conocimiento sobre la prescripción de antibióticos y el seguimiento posterior a la pancreatitis aguda. Hay déficit en el conocimiento sobre las recomendaciones de la monitorización de los signos vitales y el momento adecuado para realizar la colecistectomía ante una pancreatitis de origen biliar.
Abstract Background: Acute pancreatitis is observed more frequently in the pediatric age. Currently, there are recommendation guidelines for its proper diagnosis and treatment. The objective of this study was to evaluate the level of knowledge of the international recommendations on acute pancreatitis in pediatrics of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition in a group of pediatricians. Methods: Observational, multicenter study, through a survey applied to pediatricians and pediatric residents. Results: 48.8% of physicians had prior knowledge of the guidelines for the treatment of acute pancreatitis in children. 72.4% knew the current criteria for the diagnosis of acute pancreatitis. There were no differences in the majority of responses between pediatricians and pediatric residents. Conclusions: Although only half of the respondents followed the guidelines for diagnosis and treatment of acute pancreatitis, about three-quarters adequately use the criteria for diagnosis. There is adequate knowledge about the prescription of antibiotics and pancreatitis follow-up. There is lack of knowledge on the recommendation of monitoring vital signs and the precise time to perform cholecystectomy in the pancreatitis of biliary origin.
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Acute pancreatitis (AP) during pregnancy is a rare condition characterized by acute inflammation of pancreas due to premature activation of enzymes resulting in local pancreatic destruction and activation of an inflammatory cascade. This condition is most commonly caused by gall stones, hypertriglyceridemia, idiopathic factors. It’s very rare, incidence being 1 in 1000 to 1 in 12,000 pregnancies. Its more common in multigravida (75%) and relatively uncommon in first trimester. Patient usually present with acute severe pain abdomen radiating to back, nausea, vomiting, fever and anorexia. On examination there can be tachycardia, jaundice, epigastric tenderness, abdominal guarding and rigidity in severe cases. Serum amylase and lipase levels three times upper limit of normal value is diagnostic. Ultrasound remains imaging modality of choice. Vigorous fluid replacement is recommended. Prompt diagnosis and early treatment can prevent maternal and fetal morbidity and mortality. 23 years primigravida with 14 weeks of pregnancy came to outpatient with nausea and vomiting (10-15 episodes per day) and pain abdomen for 3 days. On abdomen examination epigastric tenderness was present. Serum amylase was 1246 Units/litre and serum lipase was 507.3 units/litre. She was given supportive care with IV fluids. Analgesics, antiemetics and antihistaminics were given. Gradually liquids were started and she recovered in 5 days.
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Acute pancreatitis （AP） is a common clinical acute abdominal disease， which is characterized by acute onset， rapid development， severe disease， many complications， and high mortality rate. It can progress to severe AP （SAP） if not treated promptly in the early stage. The pathogenesis of AP is complex and involves multiple cellular and molecular levels. It is now clear that oxidative stress and reactive oxygen species （ROS） production are involved in the physiopathological process of AP， which is associated with a low quantity and activity of antioxidant enzymes in pancreatic cells. Nuclear factor E2-related factor 2 （Nrf2） serves as the ''golden key'' to maintain redox homeostasis in tissue cells and constitutes an important signaling pathway for antioxidant response and inflammation in vivo by collaborating with downstream antioxidant enzymes such as heme oxygenase-1 （HO-1）. Traditional Chinese medicine has unique efficacy in treating diseases due to its multi-component， multi-target， multi-drug delivery， and multi-formulation characteristics. Based on the concept of synergy between traditional Chinese and Western medicine， traditional Chinese medicine is becoming a new craze in the treatment of AP. The level of oxidative stress and Nrf2/HO-1 signaling pathway in AP pancreatic tissue are in a dynamic change process， and the intervention of traditional Chinese medicine can clean ROS production， affect the inflammatory pathway， and reduce oxidative stress damage， so as to protect against pancreatic injury. This suggests that this pathway plays an important role in AP. This article reviews the recent literature on the regulation of the Nrf2/HO-1 signaling pathway by traditional Chinese medicine for AP and summarizes that the monomers of traditional Chinese medicine targeting this pathway are mainly heat-clearing and detoxifying， blood-activating and blood-stasis-removing， and Qi benefiting and middle warming， and the compounds of traditional Chinese medicine include Yinchenhao Decoction and QingYi Ⅱ， so as to provide a new direction for the prevention and treatment of AP and further drug development.
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Objective To systematically retrieve,evaluate and integrate the best evidences on the early fluid resuscitation management in the patients with acute pancreatitis(AP)at home and abroad to provide ref-erence for clinical decision.Methods The related evidences on the early fluid resuscitation management in the AP patients were retrieved by computer from the databases of BMJ Best Practice,Up To Date,JBI,National Institute for Health and Care Excellence,Registered Nurses Association of Ontario,Guideline International Network,Scottish Intercollegiate Guidelines Network,International Association of Pancreatology,American Pancreatic Association,American College of Gastroenterology,Yimaitong,Cochrane Library,PubMed,Em-bass,CINAHL,The Web of Science,CNKI,Wanfang databases.The retrieval time limit was from the data-base establishment to March 20,2022.The literatures types included thematic evidence summarization,guide-lines,evidence summaries,systematic reviews and expert consensus.The researchers conducted the literature quality evaluation.The literatures meeting the standard conducted the evidence extraction.Results A total of 13 arti-cles were included,including 3 special subject evidence summary,4 guidelines,2 evidence summary,2 systematic evalu-ation and 2 expert consensus.A total of 16 pieces of best evidence were integrated,involving 4 aspects of organization management,evaluation and monitoring,fluid infusion strategy and health education.Conclusion It is recommended to use the target-oriented therapy for early fluid resuscitation management,and perform the fluid resuscitation immediate-ly after diagnosis,according to the patient's underlying disease,disease changes and monitoring indicators,implement precise early fluid resuscitation in order to reverse pancreatic microcirculation disorder,increase tissue perfusion and improve the patient's prognosis.
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Objective To investigate the clinical features of patients with recurrent acute pancreatitis(RAP)complicated with metabolic syndrome(MS)and the influencing factors of severe disease.Methods The clini-cal data of 382 RAP patients admitted to the hospital from June 2012 to June 2022 were retrospectively analyzed,and they were divided into the MS group(n=142)and the non-MS group(n=240)according to whether they were combined with MS,and into the severe group(n=29)and the non-severe group(n=353)according to the severity.The general data,serological parameters[triglyceride(TG),total cholesterol(TC),white blood cell count(WBC),neutrophil to lymphocyte ratio(NLR),blood calcium,D-dimer(D-D),lactate dehydrogen-ase(LDH),ALT,AST]and ICU occupancy rate and total length of stay were compared among all groups.Bi-nary logistic regression was used to analyze the independent influencing factors of RAP development into se-vere disease,and receiver operating characteristic(ROC)curve was used to analyze the predictive value of each indicator for RAP development.Results Hyperlipidemia was the most common cause of RAP in MS group(66.2％),and biliary origin was the most common cause of RAP in non-MS group(44.6％).There was sig-nificant difference among different causes was statistically significant(P＜0.05).There were significant differences in age,gender,proportion of hypertension,diabetes,MS,length of stay,LDH,blood calcium,D-D and NLR levels between the critical and non-critical groups(P＜0.05).The area under the curve(AUC)of blood calcium,D-D,LDH,NLR and combined diagnosis were 0.759,0.777,0.710,0.621,and 0.841,respec-tively.The AUC of single diagnosis had a certain predictive value,but combined diagnosis had a higher predic-tive value.Conclusion The most common cause in the MS group was hyperlipidemia,and the most common cause in the non-MS group was biliary.Blood calcium.D-D,LDH,NLR are reliable indicators to predict the development of RAP into severe disease,and the accuracy of combined diagnosis is higher.
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Objective To establish an early prediction model for the diagnosis of severe acute pancreatitis based on the improved machine learning models,and to analyze its clinical value.Methods A case-control study was conducted on 352 patients with acute pancreatitis admitted to the Gastroenterology and Hepatobiliary Surgery Departments of the Army Medical Center of PLA and Emergency and Critical Care Medicine Department of No.945 Hospital of Joint Logistics Support Force of PLA from January 2014 to August 2023.According to the severity of the disease,the patients were divided into the severe group(n=88)and the non-severe group(n=264).The RUSBoost model and improved Archimead optimization algorithm was used to analyze 39 routine laboratory biochemical indicators within 48 h after admission to construct an early diagnosis and prediction model for severe acute pancreatitis.The task of feature screening and hyperparameter optimization was completed simultaneously.The ReliefF algorithm feature importance rank and multivariate logistic analysis were used to analyze the value of the selected features.Results In the training set,the area under curve(AUC)of the improved machine learning model was 0.922.In the testing set,the AUC of the improved machine learning model reached 0.888.The 4 key features of predicting severe acute pancreatitis based on the improved Archimedes optimization algorithm were C-reactive protein,blood chlorine,blood magnesium and fibrinogen level,which were consistent with the results of ReliefF algorithm feature importance ranking and multivariate logistic analysis.Conclusion The application of improved machine learning model analyzing the laboratory examination results can help to early predict the occurrence of severe acute pancreatitis.
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Objective To investigate the effect of saikosaponin A regulating myosin light chain kinase(MLCK)/myosin light chain 2(MLC2)signaling pathway on intestinal injury in rats with severe acute pan-creatitis(SAP).Methods A total of 10 rats were randomly selected as sham operation group,and the other rats were injected with sodium taurine cholate solution to construct SAP rat model.SAP rat models were ran-domly divided into SAP group,saikosaponin A group(10.0 mg/kg intraperitoneal injection of saikosaponin A)and iE-DAP group(3.5 mg/kg intraperitoneal injection of MLCK/MLC2 pathway activator iE-DAP),sai-kosaponin A+iE-DAP group(intraperitoneally injected with 10.0 mg/kg saikosaponin A+3.5 mg/kg iE-DAP),10 rats in each group were injected once a day for 1 week,sham operation group and SAP group were injected with the same amount of normal saline.The serum levels of amylase(AMY),lipase(LIP),diamine oxidase(DAO),interleukin(IL)-1β,IL-6 and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA).HE staining was used to detect the pathological morphology of ileum tis-sue in each group.The levels of oxidative stress indexes in ileum tissue were detected by ELISA.Intestinal barrier re-lated proteins and MLCK/MLC2 pathway related proteins were detected by western blot.Results Compared with SAP group,the levels of AMY,LIP,DAO,IL-1β,IL-6 and TNF-α in saikosonin A group were significantly de-creased,while the levels of AMY,LIP,DAO,IL-1β,IL-6 and TNF-α in iE-DAP group were significantly in-creased,with statistical significance(P＜0.05).Compared with SAP group,the structure of ileum tissue was improved and the pathological score of ileum tissue was significantly decreased in SA group(P＜0.05).Com-pared with SAP group,the levels of glutathione and superoxide dismutase in SA group were significantly in-creased,and the levels of malondialdehyde were significantly decreased in SA group,with statistical signifi-cance(P＜0.05).Compared with SAP group,the protein levels of MLCK,p-MLC2/MLC2 in SA group were significantly decreased,and the difference was statistically significant(P＜0.05).Conclusion Saikosaponin A may improve intestinal injury in SAP rats by down-regulating the MLCK/MLC2 signaling pathway.
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Objective To investigate the effect of miR-142-3p on the apoptosis of rat pancreatic exocrine cell line AR42J by regulating Hmgb1.Methods AR42J cells were divided into blank group(blank),acute pancreatitis model group(AP,100 nmol/L cerulein for 24 h),and then transfected with miR-142-3p mimics,mimics NC,miR-142-3p inhibitor and inhibitor NC,respectively.The cells in the model group were recorded as miR-142-3p mimics group,mimics NC group,miR-142-3p inhibitor group and inhibitor NC.The expression of miR-142-3p in cells was detected by RT-qPCR.The protein expressions of HMGB1,caspase-3,Bax and Bcl-2 were detected by Western blot.Hoechst staining was used to determine cell apoptosis.The apoptosis rate of cells was detected by flow cytometry.The targeting relationship between miR-142-3p and Hmgb1 was determined by dual luciferase reporter gene assay.Results Compared with blank control group,the expression level of miR-142-3p in the AP group was significantly down-regulated(P＜0.01),the expression level of HMGB1 and caspase-3 proteins was up-regulated(P＜0.05),the expression level of Bax protein was significantly up-regulated(P＜0.01),the expression level of Bcl-2 protein was significantly decreased(P＜0.01)and the apoptosis rate increased significantly(P＜0.01).Compared with the mimics NC group,the level of miR-142-3p in the miR-142-3p mimics group was significantly up-regulated(P＜0.01),the expression of HMGB,caspase-3 and Bax proteins was significantly down-regulated(P＜0.01),the expression of Bcl-2 protein was up-regulated(P＜0.05),and the apoptosis rate decreased signifi-cantly(P＜0.01).Compared with inhibitor NC group,the expression level of miR-142-3p in miR-142-3p inhibitor group was down-regulated(P＜0.05),the expression levels of HMGB1,caspase-3 and Bax proteins were signifi-cantly up-regulated(P＜0.01),the expression level of Bcl-2 protein was decreased(P＜0.05)and the apoptosis rate increased significantly(P＜0.01).The dual luciferase reporter gene assay showed that Hmgb1 was the target gene of miR-142-3p.Conclusions 1)The expression of miR-142-3p was low in the model group.2)miR-142-3p can inhibit the apoptosis of AR42J cells by inhibiting the expression of Hmgb1.
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Objective To explore the value of dual-phase enhanced CT radiomics in predicting post-acute pancreatitis diabetes mellitus(PPDM-A).Methods A total of 145 patients with acute pancreatitis(AP)were retrospectively collected,including 62 patients in PPDM-A group and 83 patients in non-PPDM-A group.The patients were randomly divided into training set and test set at a ratio of 7︰3,the pancreatic parenchyma in arterial phase and venous phase was delineated and the radiomics features were extracted.Vari-ance threshold method,univariate selection method and least absolute shrinkage and selection operator(LASSO)were used to screen radiomics features.The prediction performance of the model was evaluated by the area under the curve(AUC).The DeLong test was used to compare the prediction efficiency between the models,and the calibration curve and decision curve were used to evaluate the prediction efficiency of the model.Results The AUC of arterial phase model,venous phase model,combined arterial venous phase model,clinical model and radiomics combined clinical model in the training set were 0.845,0.792,0.829,0.656 and 0.862,respec-tively.The DeLong test results showed that only the difference between the radiomics combined clinical model and the clinical model in the training set and the test set was statistically significant(P<0.05).The decision curve showed that the radiomics combined clinical model had high clinical practicability in a certain range,and the calibration curve showed that the radiomics combined clinical model had the best fitting degree with the actual observation value.Conclusion Based on the dual-phase enhanced CT radiomics combined clinical model,PPDM-A can be predicted more accurately,and it can provide a certain reference value for the clinical development of per-sonalized treatment programs.
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BACKGROUND:Establishing a stable and reliable animal model of acute pancreatitis is of great significance for understanding its pathogenesis,pathophysiological characteristics,and clinical medication.Domestic and foreign studies have shown that cerulein,L-arginine,and sodium taurocholate can induce acute pancreatitis,but their pathophysiological characteristics and model characteristics are still unclear. OBJECTIVE:To establish an acute pancreatitis rat model using cerulein,L-arginine,and sodium taurocholate and to observe the changing patterns of model features at different time points. METHODS:Ninety-six healthy male Sprague-Dawley rats were randomly divided into normal group,cerulein group,L-arginine group,and sodium taurocholate group,with 24 rats in each group.Within each group,there were three subgroups(n=8 per group):12-,24-,and 48-hour subgroups.Cerulein was administered via intraperitoneal injection six times with a 1-hour interval.L-arginine was administered through two intraperitoneal injections with a 1-hour interval.Sodium taurocholate was injected for inducing acute pancreatitis models through retrograde injection into the bile-pancreatic duct.By examining the rat survival rate,gross morphology of the pancreas,calculating the pancreatic organ index,and measuring levels of amylase,lipase,alanine transaminase,aspartate transaminase,blood urea nitrogen,and creatinine,as well as observing pancreatic tissue pathological features through hematoxylin-eosin staining and conducting a pancreatic injury scoring,we evaluated the changing patterns of model features at different time points. RESULTS AND CONCLUSION:Compared with the normal group,the overall survival rate of rats was 100%in the cerulein group,88%in the L-arginine group,and 96%in the sodium taurocholate group.The pancreatic organ index was increased in all groups.Gross observation indicated that,In the cerulein group,pancreatic edema,blurred lobes,and looseness were visible.In the L-arginine group,the pancreatic glands were enlarged and thickened with patchy bleeding.In the sodium taurocholate group,pancreatic tissue showed varying degrees of congestion and edema accompanied by scattered flakes of hemorrhage and necrosis.The levels of serum alanine transaminase,aspartate transaminase,blood urea nitrogen,creatinine,amylase,and lipase in rats exhibited consistent changes.In the cerulein group,these parameters possibly peaked at 12 hours(P<0.05)and then showed a declining trend.In the L-arginine group,they reached the highest levels at 24 hours(P<0.05)and significantly decreased at 48 hours.In the sodium taurocholate group,serum amylase and lipase remained at higher levels at 12 hours with a slow decline trend(P<0.05).Compared with the normal group,microscopic examination revealed mild acinar edema and widened interlobular spaces in the cerulein group,with a higher presence of inflammatory cells.In the L-arginine group,there was widening of interlobular spaces,extensive infiltration of inflammatory cells,and patchy necrotic areas.In the sodium taurocholate group,significant pancreatic edema,structural disarray,extensive necrotic foci,and inflammatory cell infiltration were observed.Compared with the normal group,the pathological scores of induced acute pancreatitis in all three models were significantly different at each time point(P<0.05).Moreover,the pathological scores in each group increased over time,indicating a gradual worsening of pancreatic tissue damage.When comparing different models at the same time,there were differences in pathological scores,with the sodium taurocholate group having the highest scores,followed by the L-arginine group,and the cerulein group having the lowest scores.Analyzing the three models at the same time point,the most severe condition was in the sodium taurocholate group,which was characterized by pancreatic hemorrhage and necrosis,followed by the L-arginine group,which was characterized by necrosis,and the least severe condition was in the cerulein group,mainly characterized by edema.The serum biochemical index levels of the cerulein and L-arginine groups decreased at 48 hours,indicating that these two models may have a tendency to self-heal and belong to a self-limiting disease course.The serum biochemical index levels of the sodium taurocholate group decreased slowly after 12 hours.Therefore,pancreatic injury in the sodium taurocholate group might not be relieved after 48 hours or longer.
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Exosomes are extracellular vesicles that regulate various signaling pathways in the body by mediating the release of proteins, nucleic acids and lipids, thus playing an important role in pathophysiological processes such as inflammation, tumor, immunity and nervous system. More and more studies have shown that exosomal non-coding RNA (ncRNA) plays a crucial role in pancreatic diseases. This article reviews the role of exosome ncRNA in the occurrence, diagnosis and treatment of pancreatic diseases such as acute pancreatitis and pancreatic cancer, in order to provide a reference for clinical practice.
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Objective:To investigate the correlation between metabolic syndrome (MS)and recurrent acute pancreatitis (RAP).Methods:From June 1, 2012 to June 1, 2023, 463 patients with RAP (recurrent group) who visited the First Affiliated Hospital of Chongqing Medical University were retrospectively collected. The clinical data of 463 patients without RAP (non-recurrent group) during the same period were randomly selected. The patients in the recurrence group were treated at the First Affiliated Hospital of Chongqing Medical University for both initial acute pancreatitis and RAP. The differences in the proportion of patients combined with MS and its components (obesity (body mass index ≥25 kg/m 2), fasting blood triglyceride (TG) ≥1.7 mmol/L, hypertension, hyperglycemia, fasting blood high-density lipoprotein cholesterol (HDL-C) <1.04 mmol/L) between the two groups were analyzed by Chi-square test. Binary logistic regression analysis was used to identify the risk factors of acute pancreatitis recurrence. Results:Among the 463 patients in the recurrent group, there were 221 patients (47.7%) with MS, 276 patients (59.6%) with obesity, 223 patients (48.2%) with hypertension, 185 patients (40.0%) with hyperglycemia, and 365 patients (78.8%) with fasting blood TG ≥1.7 mmol/L. Among the 463 patients in the non-recurrence group, there were 95 patients (20.5%) with MS, 245 patients (52.9%) with obesity, 115 patients (24.8%) with hypertension, 92 patients (19.9%) with hyperglycemia, and 301 patients (65.0%) with fasting blood TG ≥ 1.7 mmol/L. The percentages of MS, obesity, hypertension, hyperglycemia, and fasting blood TG ≥1.7 mmol/L of the recurrent group were all higher than those of the non-recurrent group, and the differences were statistically significant ( χ2=76.27, 4.22, 54.35, 44.55, 21.90; P<0.001, =0.040, <0.001, <0.001, <0.001). There was no statistically significant difference in the percentage of patients with fasting blood HDL-C <1.04 mmol/L between the recurrent group and the non-recurrent group (68.5%, 317/463 vs. 65.4%, 303/463, P>0.05). The results of binary logistic regression analysis showed that combined with MS ( OR=3.538, 95% confidence interval (95% CI) 2.647 to 4.728), hypertension ( OR=2.700, 95% CI 2.025 to 3.602), hyperglycemia ( OR=2.228, 95% CI 1.633 to 3.039), and fasting blood TG ≥1.7 mmol/L ( OR=1.757, 95% CI 1.276 to 2.421) all significantly increased the risk of acute pancreatitis recurrence ( P<0.001, <0.001, <0.001, =0.001). Obesity was not an independent risk factor for RAP ( OR=0.967, 95% CI 0.727 to 1.286, P=0.816). Conclusion:The combination of MS, hypertension, hyperglycemia, and fasting blood TG ≥1.7 mmol/L are independent risk factors for RAP.
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Objective To investigate the protective effect and mechanism of Chaihuang Qingyi Huoxue Granules on pancreatic tissue of rats with severe acute pancreatitis,and to observe its regulation on NLRP3 inflammasome activation.Methods Sixty-four SD rats were randomly divided into sham-surgery(SO)group,severe acute pancreatitis model(SAP)group,Chaihuang Qingyi Huoxue Granules(CH)group,and MCC950(NLRP3 inhibitor)group.Each group was further divided into 12-hour and 24-hour subgroups,with rats in each group.The SAP group,CH group,and MCC950 group were retrogradely injected with 3.5%sodium taurocholate(2 mL·kg-1)into the pancreatic ducts to establish SAP model.The MCC950 group was immediately intraperitoneally injected with MCC950(1 mg·mL-1)after model preparation.After awakening from anesthesia,the CH group was administrated by gavage with Chaihuang Qingyi Huoxue Granules solution(0.35 g·mL-1)once every 6 hours.Ascites,abdominal aortic blood,and pancreatic tissue were collected at 12 hours and 24 hours after SAP model construction.The serum amylase and lipase activities were detected using an automated biochemical analyzer.HE staining was used to observe pancreatic injury.Serum levels of IL-18 and IL-1β were detected by ELISA.The expressions of gene and proteins related to the activation of NLRP3 inflammasome were analyzed by IHC,qRT-PCR and Western Blot.Results Compared with the SAP group,the pathological damage of pancreatic tissues in the CH and MCC950 groups was significantly reduced,and the pathological score was significantly reduced(P＜0.05).The levels of serum lipase,amylase,IL-18,and IL-1β were also significantly decreased(P＜0.05).After treatment with Chaihuang Qingyi Huoxue Granules or intraperitoneal injection of NLRP3 inhibitor,the positive expressions of NLRP3,ASC and Caspase-1 in pancreatic tissues,as well as the mRNA levels of NLRP3,ASC and Caspase-1,the protein levels of NLRP3,ASC,Pro-Caspase-1 and Caspase-1 were significantly reduced compared to the SAP group(P＜0.05).Conclusion Chaihuang Qingyi Huoxue Granules can inhibit the activation of NLRP3 inflammasome,reduce the mRNA and protein expressions of NLRP3,ASC and Caspase-1 in pancreatic tissues,and suppress the release of the downstream inflammatory factors IL-18 and IL-1β and alleviate pancreatitis damage in SAP model rats.
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Acute pancreatitis (AP) is one of the common acute abdominal diseases of the digestive system, and its incidence is increasing year by year in China, Europe, and the United States. Although its etiology is diverse, it follows certain pathophysiological processes and the key regulatory molecules are similar. Over the past few years, on the one hand, progress in the research was made on pancreatic acinar and ductal epithelial cells including calcium signaling pathways, impaired autophagy flux, dysfunction of mitochondria and other organelles, and endoplasmic reticulum stress imbalance. On the other hand, important progress was made in early recruitment and excessive activation of immune cells and their roles in regulating pancreatic necrosis and pancreatitis-associated multiple organ failure. All of the above-mentioned research progress has greatly enhanced our understanding of the pathogenesis and intervention strategies of AP. This article will focus on the basic research progress in the pathogenesis of AP in recent years in order to provide clinical guidance for the early treatment of AP.
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【Objective】 To observe the presence of ferroptosis in acute pancreatitis (AP) and the effect of iron ions on the NLRP3 pathway so as to explore the possible mechanisms for the protection of pancreatic alveolar cells. 【Methods】 A total of 45 male C57BL/6 mice were randomly divided into three groups (control, AP, and AP+2′2-bipyridyl). A total of 12 injections (caerulein, 50 μg/kg) were given at one-hour intervals. The AP+2′2-bipyridyl group was pretreated with 2′2-bipyridyl (20 mg/kg) for 1 hour, and then injected with caerulein. The control group was injected with an equal volume of normal saline. All of the mice were killed one hour after the last injection. Their pancreases were harvested for histopathological evaluation, immunohistochemistry analyses, and Western blotting. 【Results】 The ferroptosis inhibitor 2′2-bipyridyl could prevent the accumulation of iron ions, reduce the formation of lipid peroxides and the injury in the process of AP, and it also reduced pancreatic inflammation through NLRP3 pathway. 【Conclusion】 This experiment confirmed the real existence of ferroptosis, a form of cell death, in AP, and revealed that inhibition of ferroptosis can reduce pancreatic inflammatory damage in AP.
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【Objective】 To investigate the therapeutic effect of Huaier on acute pancreatitis (AP) and its potential mechanism. 【Methods】 A mouse model of cerulean-induced AP was used to verify the therapeutic effect of Huaier in vivo. HE staining and immunohistochemical staining were used to evaluate the histopathological changes of the pancreas, and transmission electron microscopy was used to observe the pyroptosis morphology of the pancreas. In vitro, 266-6 cell line was used as the experimental carrier to verify the protective effect of Huaier on acinar cells. Electron microscopy and Western blotting were used to evaluate the pyroptosis level of acinar cells, and ROS fluorescence probe was used to detect the oxidative stress state of acinar cells. 【Results】 Huaier significantly alleviated the severity of AP in mice. HE staining of pancreas showed that necrosis and inflammatory cell infiltration were reduced, and the level of serum amylase was decreased. Immunohistochemical staining and Western blotting showed that Huaier effectively inhibited the expressions of pyroptosis-related molecules such as NLRP3 and GSDMD in pancreatic tissue. Electron microscopy showed that Huaier could reduce the pyroptosis level of pancreatic acinar cells under inflammatory state. In addition, the level of ROS in acinar cells was significantly reduced after the intervention of Huaier, and ROS-mediated pyroptosis of acinar cells could be effectively inhibited by Huaier. 【Conclusion】 Huaier can effectively reduce the severity of AP by inhibiting ROS-mediated pyroptosis of acinar cells.
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【Objective】 To examine risk factors for acute pancreatitis (AP) in individuals with chronic alcohol consumption habits. 【Methods】 The study incorporated participants from the initial survey (2006-2010) and subsequent follow-ups (2014+) taken from the UK Biobank database, with the observation period ending on November 30, 2022. During this period, 176 individuals were newly diagnosed with AP, while 59,512 remained unaffected. Vital characteristics of the target population, such as their medical histories, surgical experiences and dietary patterns, were collected during the enrolment phase (2006-2010). The Cox proportional hazard model was employed to ascertain whether these characteristics were potent risk factors for AP. Concurrently, a subgroup from the target population with documented drinking behavior was selected. The multivariate Cox proportional hazard model was utilized to analyze the relationship of the established factors, variances in alcohol consumption, and increased alcohol intake (Δ) with the onset of AP, and whether the additional alcohol intake served as a risk factor. 【Results】 Multivariate analysis revealed that consumption quantity of cooked vegetables inversely correlated with AP risk (HR=0.44, 0.39, 0.42 and 0.41 for one, two, three and four+ tablespoons per day, respectively, as compared to non-consumers). Coffee consumption (2-3 cups per day) also reduced AP risk (HR=0.45 for 2 cups/day; HR=0.39 for 3 cups/day as compared to non-coffee drinkers). However, those with biliary disease without cholecystectomy exhibited a marked increase in AP risk (HR=7.82), which reduced albeit remained elevated for those with biliary disease post-cholecystectomy (HR=2.15). Subgroup analysis showed minimal impact of alcohol intake levels on AP incidence. Yet, increased alcohol consumption (Δ of 1 bottle/week) was linked to a heightened AP risk (HR=1.05, 95% CI:1.02-1.09, P<0.05). 【Conclusion】 Among longstanding alcohol consumers, a diet rich in cooked vegetables and moderate coffee consumption offers protective effects against AP. Conversely, biliary disease (particularly without cholecystectomy) and elevated alcohol intake present considerable risk factors for the development of this condition.
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【Objective】 To analyze the clinical features of patients with infected pancreatic necrosis (IPN) complicated with fungal infection so as to identify possible risk factors for death. 【Methods】 We analyzed the clinical data of patients with IPN admitted to Xuanwu Hospital Capital Medical University from January 1, 2017 to December 31, 2021. According to the results of pancreatic necrotic tissue and drainage fluid culture, the patients were divided into the group with fungal infection and the group without fungal infection. The baseline data, clinical features and outcomes of the two groups were compared, and the risk factors for death in patients with fungal infection were analyzed. 【Results】 We included a total of 214 patients in the study, of whom 49 patients in the fungal infection group had wider necrotic involvement, lower hematopoietic volume, and higher blood glucose at admission. Patients with fungal infection had a higher proportion of multidrug-resistant bacteria (MDRB), and hospital and ICU stay as well as parenteral nutrition duration were also longer. In the group of patients with fungal infection, the proportion of patients undergoing surgery did not increase (P>0.05), but the proportion of patients with perioperative organ failure and death was higher (P<0.05). Candida albicans (44.8%) was the most common fungus detected, followed by Candida parapsilosis (28.6%) and Candida tropicalis (8.2%). Logistic regression analysis showed that MDRB infection (OR=1.37, 95% CI:1.02-1.83), fungemia (OR=1.53, 95% CI:1.06-2.23), hyperglycemia (OR=1.65, 95% CI:1.28-2.10), new organ failure (OR=1.65, 95% CI:1.19-2.29) and bleeding complications (OR=1.64, 95% CI:1.28-2.10) after surgery were risk factors for death in patients with fungal infection. 【Conclusion】 Fungal infection increases mortality in patients with IPN and the incidence of new organ failure after surgery. Attention to fungemia, MDRB infection, hyperglycemia, organ failure and postoperative bleeding can help reduce the risk of death.
ABSTRACT
OBJECTIVE To study the effects of leonurine on pancreatic injury in rats with severe acute pancreatitis （SAP）， and to explore its mechanism based on the high-mobility group box 1 （HMGB1）/receptor for advanced glycation end products （RAGE） signaling pathway. METHODS SAP rat model was constructed by injecting 5% sodium taurocholate into the bile duct of the pancreas. Model rats were randomly divided into model group， low dose leonurine group （8 mg/kg）， high dose leonurine group （16 mg/kg）， HMGB1 overexpression group （8 μg/kg）， and high dose leonurine+HMGB1 overexpression group （16 mg/kg+8 μg/kg）， with 14 rats in each group. Another 14 rats were selected as the sham operation group. Rats in each group were injected with corresponding drugs or normal saline via abdominal cavity or tail vein once a day for 5 consecutive days. After the last administration， the levels of serum amylase （AMS） and lipase （LPS） were detected； the pathological injury of pancreatic tissue was observed； the levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， malondialdehyde （MDA） and superoxide dismutase （SOD）， mRNA and protein expressions of HMGB1 and RAGE in pancreatic tissues were detected. RESULTS Compared with model group， the structure of pancreatic tissue in rats gradually recovered in low and high dose leonurine groups； inflammatory cell infiltration gradually decreased； the pathological injury score and the levels of AMS， LPS， TNF-α， IL-6， MDA， the mRNA and protein expressions of HMGB1 and RAGE were significantly decreased， while the SOD levels were significantly increased （P＜0.05）. The high dose leonurine group showed more significant improvement （P＜0.05）； the pathological damage of pancreatic tissue in the HMGB1 overexpression group worsened， and except for a decrease in SOD levels， all other quantitative indicators increased significantly （P＜0.05）. Overexpression of HMGB1 could reduce the improvement effect of high dose leonurine on the above indexes in SAP rats （P＜0.05）. CONCLUSIONS Leonurine may alleviate pancreatic injury， inflammation and oxidative stress in pancreatic tissue of rats with SAP by inhibiting the HMGB1/RAGE signaling pathway.
ABSTRACT
Objective: Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, COVID-19 vaccination has substantially reduced mortality and hospitalization rates worldwide, with rare adverse events reported in clinical settings. Herein, we present a case of acute pancreatitis complicated by diabetic ketoacidosis (DKA) following the third COVID-19 vaccination dose.Patient: A 72-year-old male with a history of diabetes mellitus developed generalized fatigue, mild epigastric pain, nausea, and frequent vomiting after receiving the COVID-19 vaccine.Results: Blood analysis revealed elevated levels of pancreatic enzymes, hyperglycemia, and acidemia. Computed tomography revealed evidence of acute pancreatitis, leading to a diagnosis of both DKA and acute pancreatitis. Treatment with a large volume of saline and intravenous insulin improved both DKA and acute pancreatitis. After a thorough examination, no other factors capable of causing acute pancreatitis were identified. Hence, we concluded that acute pancreatitis was induced by COVID-19 vaccination.Conclusion: Acute pancreatitis is a rare but potentially life-threatening adverse event associated with COVID-19 vaccination. Delaying the treatment or diagnosis of acute pancreatitis can increase mortality risk in patients with both acute pancreatitis and DKA. Hence, it is crucial for healthcare professionals to consider the potential occurrence of acute pancreatitis and DKA following COVID-19 vaccination.