Comparative transcriptomic analysis reveals the molecular changes of acute pancreatitis in experimental models

BACKGROUND Acute pancreatitis(AP)encompasses a spectrum of pancreatic inflammatory conditions,ranging from mild inflammation to severe pancreatic necrosis and multisystem organ failure.Given the challenges associated with obtaining human pancreatic samples,research on AP predominantly relies on animal models.In this study,we aimed to elucidate the fundamental molecular mechanisms underlying AP using various AP models.AIM To investigate the shared molecular changes underlying the development of AP across varying severity levels.METHODS AP was induced in animal models through treatment with caerulein alone or in combination with lipopolysaccharide(LPS).Additionally,using Ptf1αto drive the specific expression of the hM3 promoter in pancreatic acinar cells transgenic C57BL/6J-hM3/Ptf1α(cre)mice were administered Clozapine N-oxide to induce AP.Subsequently,we conducted RNA sequencing of pancreatic tissues and validated the expression of significantly different genes using the Gene Expression Omnibus(GEO)database.RESULTS Caerulein-induced AP showed severe inflammation and edema,which were exacerbated when combined with LPS and accompanied by partial pancreatic tissue necrosis.Compared with the control group,RNA sequencing analysis revealed 880 significantly differentially expressed genes in the caerulein model and 885 in the caerulein combined with the LPS model.Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Set Enrichment Analysis indicated substantial enrichment of the TLR and NOD-like receptor signaling pathway,TLR signaling pathway,and NF-κB signaling pathway,alongside elevated levels of apoptosis-related pathways,such as apoptosis,P53 pathway,and phagosome pathway.The significantly elevated genes in the TLR and NOD-like receptor signaling pathways,as well as in the apoptosis pathway,were validated through quantitative real-time PCR experiments in animal models.Validation from the GEO database revealed that only MYD88 concurred in both mouse pancreatic tissue and human AP peripheral blood,while TLR1,TLR7,RIPK3,and OAS2 genes exhibited marked elevation in human AP.The genes TUBA1A and GADD45A played significant roles in apoptosis within human AP.The transgenic mouse model hM3/Ptf1α(cre)successfully validated significant differential genes in the TLR and NOD-like receptor signaling pathways as well as the apoptosis pathway,indicating that these pathways represent shared pathological processes in AP across different models.CONCLUSION The TLR and NOD receptor signaling pathways play crucial roles in the inflammatory progression of AP,notably the MYD88 gene.Apoptosis holds a central position in the necrotic processes of AP,with TUBA1A and GADD45A genes exhibiting prominence in human AP.

Impact of metabolic syndrome components on clinical outcomes in hypertriglyceridemia-induced acute pancreatitis

BACKGROUND The incidence of hypertriglyceridemia(HTG)-induced acute pancreatitis(AP)is steadily increasing in China,becoming the second leading cause of AP.Clinical complications and outcomes associated with HTG-AP are generally more severe than those seen in AP caused by other etiologies.HTG-AP is closely linked to metabolic dysfunction and frequently coexists with metabolic syndrome or its components.However,the impact of metabolic syndrome components on HTGAP clinical outcomes remains unclear.AIM To investigate the impact of metabolic syndrome component burden on clinical outcomes in HTG-AP.METHODS In this retrospective study of 255 patients diagnosed with HTG-AP at the First Affiliated Hospital of Guangxi Medical University,we collected data on patient demographics,clinical scores,complications,and clinical outcomes.Subsequently,we analyzed the influence of the presence and number of individual metabolic syndrome components,including obesity,hyperglycemia,hypertension,and low high-density lipoprotein cholesterol(HDL-C),on the aforementioned parameters in HTG-AP patients.RESULTS This study found that metabolic syndrome components were associated with an increased risk of various complications in HTG-AP,with low HDL-C being the most significant risk factor for clinical outcomes.The risk of complications increased with the number of metabolic syndrome components.Adjusted for age and sex,patients with highcomponent metabolic syndrome had significantly higher risks of renal failure[odds ratio(OR)=3.02,95%CI:1.12-8.11)],SAP(OR=5.05,95%CI:2.04-12.49),and intensive care unit admission(OR=6.41,95%CI:2.42-16.97)compared to those without metabolic syndrome.CONCLUSION The coexistence of multiple metabolic syndrome components can synergistically worsen the clinical course of HTGAP,making it crucial to monitor these components for effective disease management.

Computerized tomography-guided therapeutic percutaneous puncture catheter drainage-combined with somatostatin for severe acute pancreatitis: An analysis of efficacy and safety

BACKGROUND Severe acute pancreatitis(SAP),a condition with rapid onset,critical condition and unsatisfactory prognosis,poses a certain threat to human health,warranting optimization of relevant treatment plans to improve treatment efficacy.AIM To evaluate the efficacy and safety of computerized tomography-guided the-rapeutic percutaneous puncture catheter drainage(CT-TPPCD)combined with somatostatin(SS)in the treatment of SAP.METHODS Forty-two SAP patients admitted to The Second Affiliated Hospital of Fujian Medical University from June 2020 to June 2023 were selected.On the basis of routine treatment,20 patients received SS therapy(control group)and 22 patients were given CT-TPPCD plus SS intervention(research group).The efficacy,safety(pancreatic fistula,intra-abdominal hemorrhage,sepsis,and organ dysfunction syndrome),abdominal bloating and pain relief time,bowel recovery time,hospital stay,inflammatory indicators(C-reactive protein,interleukin-6,and pro-calcitonin),and Acute Physiology and Chronic Health Evaluation(APACHE)II score of both groups were evaluated for comparison.RESULTS Compared with the control group,the research group had a markedly higher total effective rate,faster abdominal bloating and pain relief and bowel recovery,INTRODUCTION Pancreatitis,an inflammatory disease occurring in the pancreatic tissue,is classified as either acute or chronic and is associated with high morbidity and mortality,imposing a socioeconomic burden[1,2].The pathogenesis of this disease involves early protease activation,activation of nuclear factor kappa-B-related inflammatory reactions,and infiltration of immune cells[3].Severe acute pancreatitis(SAP)is a serious condition involving systemic injury and subsequent possible organ failure,accounting for 20%of all acute pancreatitis cases[4].SAP is also characterized by rapid onset,critical illness and unsatisfactory prognosis and is correlated with serious adverse events such as systemic inflammatory response syn-drome and acute lung injury,threatening the health of patients[5,6].Therefore,timely and effective therapeutic inter-ventions are of great significance for improving patient prognosis and ensuring therapeutic effects.Somatostatin(SS),a peptide hormone that can be secreted by endocrine cells and the central nervous system,is in-volved in the regulatory mechanism of glucagon and insulin synthesis in the pancreas[7].It has complex and pleiotropic effects on the gastrointestinal tract,which can inhibit the release of gastrointestinal hormones and negatively modulate the exocrine function of the stomach,pancreas and bile,while exerting a certain influence on the absorption of the di-gestive system[8,9].SS has shown certain clinical effectiveness when applied to SAP patients and can regulate the severity of SAP and immune inflammatory responses,and this regulation is related to its influence on leukocyte apoptosis and adhesion[10,11].Computerized tomography-guided therapeutic percutaneous puncture catheter drainage(CT-TPPCD)is a surgical procedure to collect lesion fluid and pus samples from necrotic lesions and perform puncture and drainage by means of CT image examination and precise positioning[12].In the research of Liu et al[13],CT-TPPCD applied to pa-tients undergoing pancreatic surgery contributes to not only good curative effects but also a low surgical risk.Baudin et al[14]also reported that CT-TPPCD has a clinical success rate of 64.6%in patients with acute infectious necrotizing pan-creatitis,with nonfatal surgery-related complications found in only two cases,suggesting that this procedure is clinically effective and safe in the treatment of the disease.In light of the limited studies on the efficacy and safety of SS plus CT-TPPCD in SAP treatment,this study performed a relevant analysis to improve clinical outcomes in SAP patients.

Severe acute pancreatitis complicated with intra-abdominal infection secondary to trauma:A case report

BACKGROUND Pancreatic trauma(PT)is rare among traumatic injuries and has a low incidence,but it can still lead to severe infectious complications,resulting in a high mortality rate.Acute pancreatitis(AP)is a common complication after PT,and when combined with organ dysfunction and sepsis,it will result in a poorer prognosis.CASE SUMMARY We report a 25-year-old patient with multiple organ injuries,including the pancreas,due to abdominal trauma,who developed necrotising pancreatitis secondary to emergency caesarean section,combined with intra-abdominal infection(IAI).The patient underwent performed percutaneous drainage,pancreatic necrotic tissue debridement,and abdominal infection foci debridement on the patient.CONCLUSION We report a case of severe AP and IAI secondary to trauma.This patient was managed by a combination of conservative treatment such as antibiotic therapy and fluid support with surgery,and a better outcome was obtained.

Chaiqin Chengqi Decoction as an adjuvant treatment for mild/moderately severe hypertriglyceridemic acute pancreatitis: A retrospective study

Hypertriglyceridemia is the third leading cause of acute pancreatitis(AP),and its incidence is increasing.Due to its relatively insidious etiology,it is easy to be ignored in the early stages.In China,Chaiqin Chengqi Decoction(CQCQD)has long been employed for treating AP.AIM To evaluate the effectiveness of CQCQD in patients diagnosed with mild/moderately severe hypertriglyceridemic AP(HTG-AP).METHODS In this study,the clinical data of 39 patients with HTG-AP admitted from January 2019 to November 2022 were collected.The changes of blood lipids,gastrointestinal symptoms,and abdominal pain before and after treatment were analyzed and compared between the two groups.RESULTS Twenty patients were treated with the conventional HTG-AP regimen,and 19 patients were additionally treated with CQCQD.After receiving treatment,the triglycerides(TG)level of the CQCQD group was lower than that of the CQCQD group(3.14±0.25 mmol/L vs 4.96±0.47 mmol/L,P<0.01).After 3 d of treatment,the patients in the CQCQD group had more bowel movements than the control group(2.51±0.25 times vs 1.00±0.17 times,P=0.01).The gastrointestinal function of most patients returned to normal,and the acute gastrointestinal injury score was significantly lower than that of the control group(0.11±0.07 vs 0.42±0.11,P<0.01).CONCLUSION In patients with HTG-AP,CQCQD can significantly reduce the TG level,shorten the recovery time of defecation,significantly improve the gastrointestinal function.

Different timing for abdominal paracentesis catheter placement and drainage in severe acute pancreatitis complicated by intraabdominal fluid accumulation

BACKGROUND Non-surgical methods such as percutaneous drainage are crucial for the treatment of patients with severe acute pancreatitis(SAP).However,there is still an ongoing debate regarding the optimal timing for abdominal paracentesis catheter place-ment and drainage.AIM To explore the influence of different timing for abdominal paracentesis catheter placement and drainage in SAP complicated by intra-abdominal fluid accumu-lation.METHODS Using a retrospective approach,184 cases of SAP complicated by intra-abdominal fluid accumulation were enrolled and categorized into three groups based on the timing of catheter placement:group A(catheter placement within 2 d of symptom onset,n=89),group B(catheter placement between days 3 and 5 after symptom onset,n=55),and group C(catheter placement between days 6 and 7 after symptom onset,n=40).The differences in progression rate,mortality rate,and the number of cases with organ dysfunction were compared among the three groups.RESULTS The progression rate of group A was significantly lower than those in groups B and groups C(2.25%vs 21.82%and 32.50%,P<0.05).Further,the proportion of patients with at least one organ dysfunction in group A was significantly lower than those in groups B and groups C(41.57%vs 70.91%and 75.00%,P<0.05).The mortality rates in group A,group B,and group C were similar(P>0.05).At postoperative day 3,the levels of C-reactive protein(55.41±19.32 mg/L vs 82.25±20.41 mg/L and 88.65±19.14 mg/L,P<0.05),procalcitonin(1.36±0.51 ng/mL vs 3.20±0.97 ng/mL and 3.41±0.98 ng/mL,P<0.05),tumor necrosis factor-alpha(15.12±6.63 pg/L vs 22.26±9.96 pg/L and 23.39±9.12 pg/L,P<0.05),interleukin-6(332.14±90.16 ng/L vs 412.20±88.50 ng/L and 420.08±87.65ng/L,P<0.05),interleukin-8(415.54±68.43 ng/L vs 505.80±66.90 ng/L and 510.43±68.23ng/L,P<0.05)and serum amyloid A(270.06±78.49 mg/L vs 344.41±81.96 mg/L and 350.60±80.42 mg/L,P<0.05)were significantly lower in group A compared to those in groups B and group C.The length of hospital stay in group A was significantly lower than those in groups B and group C(24.50±4.16 d vs 35.54±6.62 d and 38.89±7.10 d,P<0.05).The hospitalization expenses in group A were also significantly lower than those in groups B and groups C[2.70(1.20,3.55)ten-thousand-yuan vs 5.50(2.98,7.12)ten-thousand-yuan and 6.00(3.10,8.05)ten-thousand-yuan,P<0.05).The incidence of complications in group A was markedly lower than that in group C(5.62%vs 25.00%,P<0.05),and similar to group B(P>0.05).CONCLUSION Percutaneous catheter drainage for the treatment of SAP complicated by intra-abdominal fluid accumulation is most effective when performed within 2 d of onset.

Enhancing predictive accuracy in hypertriglyceridemia-induced acute pancreatitis:Role of red cell distribution width and prospective studies

This letter addresses the study titled“Red cell distribution width:A predictor of the severity of hypertriglyceridemia-induced acute pancreatitis”by Lv et al published in the World Journal of Experimental Medicine.The study offers a valuable analysis of red cell distribution width(RDW)as a predictive marker for persistent organ failure in patients with hypertriglyceridemia-induced acute pancreatitis.The study results suggest that RDW,combined with the Bedside Index for Severity in Acute Pancreatitis score,could enhance the predictive accuracy for severe outcomes.Further investigation into the role of RDW in different severities of acute pancreatitis is recommended.Additionally,the need for large-scale and multicenter prospective studies to validate these findings is emphasized.

Assessment of early factors for identification or prediction severe acute pancreatitis in pregnancy

BACKGROUND Acute pancreatitis in pregnancy(APIP)is a rare and serious condition,and severe APIP(SAPIP)can lead to pancreatic necrosis,abscess,multiple organ dysfunction,and other adverse maternal and infant outcomes.Therefore,early identification or prediction of SAPIP is important.AIM To assess factors for early identification or prediction of SAPIP.METHODS The clinical data of patients with APIP were retrospectively analyzed.Patients were classified with mild acute pancreatitis or severe acute pancreatitis,and the clinical characteristics and laboratory biochemical indexes were compared between the two groups.Logical regression and receiver operating characteristic curve analyses were performed to assess the efficacy of the factors for identification or prediction of SAPIP.RESULTS A total of 45 APIP patients were enrolled.Compared with the mild acute pancreatitis group,the severe acute pancreatitis group had significantly increased(P<0.01)heart rate(HR),hemoglobin,neutrophil ratio(NEUT%),and neutrophil–lymphocyte ratio(NLR),while lymphocytes were significantly decreased(P<0.01).Logical regression analysis showed that HR,NEUT%,NLR,and lymphocyte count differed significantly(P<0.01)between the groups.These may be factors for early identification or prediction of SAPIP.The area under the curve of HR,NEUT%,NLR,and lymphocyte count in the receiver operating characteristic curve analysis was 0.748,0.732,0.821,and 0.774,respectively.The combined analysis showed that the area under the curve,sensitivity,and specificity were 0.869,90.5%,and 70.8%,respectively.CONCLUSION HR,NEUT%,NLR,and lymphocyte count can be used for early identification or prediction of SAPIP,and the combination of the four factors is expected to improve identification or prediction of SAPIP.

Application of psychological intervention in intensive care unit nursing for patients with severe acute pancreatitis

BACKGROUND Severe acute pancreatitis(SAP)is a familiar critical disease in the intensive care unit(ICU)patients.Nursing staff are important spiritual pillars during the treatment of patients,and in addition to routine nursing,more attention needs be paid to the patient’s psychological changes.AIM To investigate the effects of psychological intervention in ICU patients with SAP.METHODS One hundred ICU patients with SAP were hospitalized in the authors’hospital between 2020 and 2023 were selected,and divided into observation and control groups per the hospitalization order.The control and observation groups received routine nursing and psychological interventions,respectively.Two groups are being compared,using the Self-rating Anxiety Scale(SAS),Self-Determination Scale(SDS),Acute Physiology and Chronic Health Evaluation(APACHE)Ⅱ,and 36-item Short Form Health Survey(SF-36)scores;nursing satisfaction of patients;ICU care duration;length of stay;hospitalization expenses;and the incidence of complications.RESULTS After nursing,the SDS,SAS,and APACHEⅡ scores in the experimental group were significantly lower than in the control group(P<0.05).The SF-36 scores in the observation group were significantly higher than those in the control group(P<0.05).The nursing satisfaction of patients in the experimental group was 94.5%,considerably higher than that of 75.6% in the control group(P<0.05).The ICU care duration,length of stay,and hospitalization expenses in the observation group were significantly lower than those in the control group,and the incidence of complications was lower(P<0.05).CONCLUSION For patients with SAP,the implementation of standardized psychological intervention measures can effectively alleviate adverse psychological conditions.

A Study on the Application of Evidence-Based Nursing in The Care of Patients with Severe Acute Pancreatitis

Objective: To explore the application research of evidence-based nursing in the care of patients with severe acute pancreatitis. Methods: This study focuses on evidence-based nursing care of severe acute pancreatitis. Patients with severe acute pancreatitis who received treatment in our hospital were selected, from which 80 cases were chosen for detailed analysis. The patients were randomly grouped into a control group (conventional nursing care) and a study group (evidence-based nursing care), with 40 patients each. Relevant research data were recorded during the nursing process, analyzed, and used as research indicators. Results: The hospitalization time and morbidity and mortality rate of the research group were shorter than those of the control group, and the recovery rate was higher than that of the control group (P < 0.05). Patient satisfaction with nursing care in the observation group was higher than in the control group (P < 0.05). Conclusion: For patients with severe acute pancreatitis, the use of evidence-based nursing methods effectively reduced the patient’s mortality rate, improved its curative effect, and also shortened the patient’s hospitalization time.

Visceral adipose tissue predicts severity and prognosis of acute pancreatitis in obese patients

Acute pancreatitis is a common systemic inflammatory disease, manifested by a spectrum of severity, ranging from mild in the majority of patients to severe acute pancreatitis. Patients with severe acute pancreatitis suffer from severe local and systemic complications and organ failure, leading to a poor prognosis. The early recognition of the severe condition is important to improve prognosis. Obesity has risen in tandem with an increase in the severity of acute pancreatitis in recent years. Studies have revealed that adipose tissue, particularly visceral adipose tissue is associated with the prognosis of acute pancreatitis. This review discussed the role of visceral adipose tissue in obese patients with acute pancreatitis and explored the possible mechanism involved.

Early systemic anticoagulation reduces hospital readmission in acute necrotizing pancreatitis patients:A retrospective cohort study

Background:Early systemic anticoagulation(SAC)is a common practice in acute necrotizing pancreatitis(ANP),and its impact on in-hospital clinical outcomes had been assessed.However,whether it affects long-term outcomes is unknown.This study aimed to evaluate the effect of SAC on 90-day readmission and other long-term outcomes in ANP patients.Methods:During January 2013 and December 2018,ANP patients admitted within 7 days from the onset of abdominal pain were screened.The primary outcome was 90-day readmission after discharge.Cox proportional-hazards regression model and mediation analysis were used to define the relationship between early SAC and 90-day readmission.Results:A total of 241 ANP patients were enrolled,of whom 143 received early SAC during their hospitalization and 98 did not.Patients who received early SAC experienced a lower incidence of splanchnic venous thrombosis(SVT)[risk ratio(RR)=0.40,95%CI:0.26-0.60,P<0.01]and lower 90-day readmission with an RR of 0.61(95%CI:0.41-0.91,P=0.02)than those who did not.For the quality of life,patients who received early SAC had a significantly higher score in the subscale of vitality(P=0.03)while the other subscales were all comparable between the two groups.Multivariable Cox regression model showed that early SAC was an independent protective factor for 90-day readmission after adjusting for potential confounders with a hazard ratio of 0.57(95%CI:0.34-0.96,P=0.04).Mediation analysis showed that SVT mediated 37.0%of the early SAC-90-day readmission causality.Conclusions:The application of early SAC may reduce the risk of 90-day readmission in the survivors of ANP patients,and reduced SVT incidence might be the primary contributor.

Implementation of gastrointestinal function protection in severe acute pancreatitis

Severe acute pancreatitis(SAP)is a serious systemic disease associated with strong local inflammatory reactions and serious systemic pathophysiological disorders caused by trypsin spillover.Patients with SAP are prone to exhibit gastrointestinal dysfunction.Meanwhile,gastrointestinal dysfunction further aggravates the systemic inflammatory response and metabolic abnormalities,resulting in a more critical condition of SAP.Gastrointestinal dysfunction is considered to be the“trigger”of multiple organ dysfunction syndrome[1].Thus,it is important to maintain gastrointestinal homeostasis in the treatment of SAP.

Red cell distribution width: A predictor of the severity of hypertriglyceridemia-induced acute pancreatitis

BACKGROUND Compared with patients with other causes of acute pancreatitis,those with hypertriglyceridemia-induced acute pancreatitis(HTG-AP)are more likely to develop persistent organ failure(POF).Therefore,recognizing the individuals at risk of developing POF early in the HTG-AP process is a vital for improving outcomes.Bedside index for severity in acute pancreatitis(BISAP),a simple parameter that is obtained 24 h after admission,is an ideal index to predict HTG-AP severity;however,the suboptimal sensitivity limits its clinical application.Hence,current clinical scoring systems and biochemical parameters are not sufficient for predicting HTG-AP severity.AIM To elucidate the early predictive value of red cell distribution width(RDW)for POF in HTG-AP.METHODS In total,102 patients with HTG-AP were retrospectively enrolled.Demographic and clinical data,including RDW,were collected from all patients on admission.RESULTS Based on the Revised Atlanta Classification,37(33%)of 102 patients with HTG-AP were diagnosed with POF.On admission,RDW was significantly higher in patients with HTG-AP and POF than in those without POF(14.4%vs 12.5%,P<0.001).The receiver operating characteristic curve demonstrated a good discrim-inative power of RDW for POF with a cutoff of 13.1%,where the area under the curve(AUC),sensitivity,and specificity were 0.85,82.4%,and 77.9%,respectively.When the RDW was≥13.1%and one point was added to the original BISAP to obtain a new BISAP score,we achieved a higher AUC,sensitivity,and specificity of 0.89,91.2%,and 67.6%,respectively.CONCLUSION RDW is a promising predictor of POF in patients with HTG-AP,and the addition of RDW can promote the sensitivity of BISAP.

Metabolic syndrome and acute pancreatitis:Current status and future prospects

Rising incidence of a complicated disorder with a multifarious etiology is acute pancreatitis.Growing numbers of cases of acute pancreatitis are linked to obesity,hyperlipidemia,hyperglycemia,hypertension,and other metabolic diseases.Trends driven by better living standards and unhealthy lifestyle choices both in China and abroad.Furthermore common diagnosis for many patients is metabolic syndrome.Predicting the adverse effect of metabolic syndrome on the severity and prognosis of acute pancreatitis is a main focus of present clinical research.Our next studies seek to investigate the fundamental causes of this link and create preventative plans meant to lower the incidence of pancreatitis linked to meta-bolic syndrome and enhance the prognosis.

Transfection of 12/15-lipoxygenase effectively alleviates inflammatory responses during experimental acute pancreatitis

BACKGROUND Acute pancreatitis(AP),the initially triggered inflammatory process in the pancreas,can be life-threatening.It has been reported that 15-lipoxygenase may promote the removal of damaged intracellular components,maintain intracellular homeostasis,and promote apoptosis by upregulating the activity of caspases.Despite an increased understanding of the lipoxygenase pathway in inflammation and immune diseases,the role of the Alox15 gene product in modulating the inflammatory changes during AP is not well defined.AIM To investigate the effect of Alox15 expression in cerulein-induced AP in rats.METHODS Model rats were transfected with Alox15 by injecting a recombinant lentivirus vector encoding Alox15 into the left gastric artery before inducing AP.The expression of Alox15 was then assessed at the mRNA and protein levels.RESULTS Our in vivo results showed that serum amylase activity and pancreatic tissue water content were significantly reduced in Alox15-transfected rats.Further,the mRNA expression levels of tumor necrosis factor alpha,interleukin(IL)-1β,IL-6,and monocyte chemoattractant protein-1,as well as the protein expression of nuclear factor kappa B in pancreatic tissue were reduced.Additionally,we observed an upregulation of cleaved caspase-3 that implies an induction of apoptosis in pancreatic cells.The transfection of Alox15 resulted in a lower number of autophagic vacuoles in AP.CONCLUSION Our findings demonstrate a regulatory role of Alox15 in apoptosis and autophagy,making it a potential therapeutic target for AP.

Mesenteric adipose tissue B lymphocytes promote intestinal injury in severe acute pancreatitis by mediating enteric pyroptosis

Background:Visceral adipose tissue(VAT)has been linked to the severe acute pancreatitis(SAP)prognosis,although the underlying mechanism remains unclear.It has been reported that pyroptosis worsens SAP.The present study aimed to verify whether mesenteric adipose tissue(MAT,a component of VAT)can cause secondary intestinal injury through the pyroptotic pathway.Methods:Thirty-six male Sprague Dawley(SD)rats were divided into six different groups.Twelve rats were randomly divided into the SAP and control groups.We monitored the changes of MAT and B lymphocytes infiltration in MAT of SAP rats.Twelve SAP rats were injected with MAT B lymphocytes or phosphate buffer solution(PBS).The remaining twelve SAP rats were first injected with MAT B lymphocytes,and then with MCC950(NLRP3 inhibitor)or PBS.We collected blood and tissue samples from pancreas,gut and MAT for analysis.Results:Compared to the control rats,the SAP group showed inflammation in MAT,including higher expression of tumor necrosis factor(TNF-α)and interleukin-6(IL-6),lower expression of IL-10,and histological changes.Flow cytometry analysis revealed B lymphocytes infiltration in MAT but not T lymphocytes and macrophages.The SAP rats also exhibited intestinal injury,characterized by lower expression of zonula occludens-1(ZO-1)and occludin,higher levels of lipopolysaccharide and diamine oxidase,and pathological changes.The expression of NLRP3 and n-GSDMD,which are responsible for pyroptosis,was increased in the intestine of SAP rats.The injection of MAT B lymphocytes into SAP rats exacerbated the inflammation in MAT.The upregulation of pyroptosis reduced tight junction in the intestine,which contributed to the SAP progression,including higher inflammatory indicators and worse histological changes.The administration of MCC950 to SAP+MAT B rats downregulated pyroptosis,which subsequently improved the intestinal barrier and ameliorated inflammatory response of SAP.Conclusions:In SAP,MAT B lymphocytes aggravated local inflammation,and promoted the injury to the intestine through the enteric pyroptotic pathway.

Reactive oxygen species and oxidative stress in acute pancreatitis:Pathogenesis and new therapeutic interventions

Acute pancreatitis(AP)is a common acute gastrointestinal disorder affecting approximately 20%of patients with systemic inflammatory responses that may cause pancreatic and peripancreatic fat necrosis.This condition often progresses to multiple organ failure,significantly increasing morbidity and mortality.Oxidative stress,characterized by an imbalance between the body’s reactive oxygen species(ROS)and antioxidants,activates the inflammatory signaling pathways.Although the pathogenesis of AP is not fully understood,ROS are increasingly recognized as critical in the disease's progression and development.Modulating the oxidative stress pathway has shown efficacy in mitigating the progression of AP.Despite numerous basic studies examining this pathway,comprehensive reviews of recent research remain sparse.This systematic review offers an in-depth examination of the critical role of oxidative stress in the pathogenesis and progression of AP and evaluates the therapeutic potential of antioxidant interventions in its management.

Primary hyperparathyroidism-induced acute pancreatitis in pregnancy:A systematic review with a diagnostic-treatment algorithm

BACKGROUND Primary hyperparathyroidism(PHPT)-induced acute pancreatitis(AP)during pregnancy has rarely been described.Due to this rarity,there are no diagnostic or treatment algorithms for pregnant patients.AIM To determine appropriate diagnostic methods,therapeutic options,and factors related to maternal and fetal outcomes for PHPT-induced AP in pregnancy.METHODS A literature search of articles in English,Japanese,German,Spanish,and Italian was performed using PubMed(1946-2023),PubMed Central(1900-2023),and Google Scholar.The Preferred Reporting Items for Systematic reviews and Meta-Analyses(PRISMA)protocol was followed.The search terms included“pancreatite acuta,”“iperparatiroidismo primario,”“gravidanza,”“travaglio,”“puerperio,”“postpartum,”“akute pankreatitis,”“primärer hyperparathyreoidismus,”“Schwangerschaft,”“Wehen,”“Wochenbett,”“pancreatitis aguda,”“hiperparatiroidismo primario,”“embarazo,”“parto,”“puerperio,”“posparto,”“acute pancreatitis,”“primary hyperparathyroidism,”“pregnancy,”“labor,”“puerperium,”and“postpartum.”Additional studies were identified by reviewing the reference lists of retrieved studies.Demographic,imaging,surgical,obstetric,and outcome data were obtained.RESULTS Fifty-four cases were collected from the 51 studies.The median maternal age was 29 years.PHPT-induced AP starts at the 20th gestational week;higher gestational weeks were seen in mothers who died(mean gestational week 28).Median values of amylase(1399,Q1-Q3=519-2072),lipase(2072,Q1-Q3=893-2804),serum calcium(3.5,Q1-Q3=3.1-3.9),and parathormone(PTH)(384,Q1-Q3=123-910)were reported.In 46 cases,adenoma was the cause of PHPT,followed by 2 cases of carcinoma and 1 case of hyperplasia.In the remaining 5 cases,the diagnosis was not reported.Neck ultrasound was positive in 34 cases,whereas sestamibi was performed in 3 cases,and neck computed tomography or magnetic resonance imaging was performed in 9 cases(the enlarged parathyroid gland was not localized in 3 cases).Surgery was the preferred treatment during pregnancy in 33 cases(median week of gestation 25,Q1-Q3=20-30)and postpartum in 12 cases.The timing was not reported in the remaining 9 cases,or surgery was not performed.AP was managed surgically in 11 cases and conservatively in 43(79.6%)cases.Maternal and fetal mortality was 9.3%(5 cases).Surgery was more common in deceased mothers(60.0%vs 16.3%;P=0.052),and PTH values tended to be higher in this group(910 pg/mL vs 302 pg/mL;P=0.059).Maternal mortality was higher with higher serum lipase levels and earlier delivery week.Higher calcium(4.1 mmol/L vs 3.3 mmol/L;P=0.009)and PTH(1914 pg/mL vs 302 pg/mL;P=0.003)values increased fetal/child mortality,as well as abortions(40.0%vs 0.0%;P=0.007)and complex deliveries(60.0%vs 8.2%;P=0.01).CONCLUSION If serum calcium is not tested during admission,definitive diagnosis of PHPT-induced AP in pregnancy is delayed,while early diagnosis and immediate intervention lead to excellent maternal and fetal outcomes.

ALKBH5 suppresses autophagic flux via N6-methyladenosine demethylation of ZKSCAN3 mRNA in acute pancreatitis

BACKGROUND Increasing evidence has demonstrated that N6-methyladenosine(m6A)RNA modification plays an essential role in a wide range of pathological conditions.Impaired autophagy is a critical hallmark of acute pancreatitis(AP).AIM To explore the role of the m6A modification of ZKSCAN3 in the regulation of autophagy in AP.METHODS The AP mouse cell model was established by cerulein-treated mouse pancreatic acinar cells(MPC-83),and the results were confirmed by the levels of amylase and inflammatory factors.Autophagy activity was evaluated by specific identification of the autophagy-related microstructure and the expression of autophagy-related genes.ZKSCAN3 and ALKBH5 were knocked down to study the function in AP.A m6A RNA binding protein immunoprecipitation assay was used to study how the m6A modification of ZKSCAN3 mRNA is regulated by ALKBH.RESULTS The increased expression of amylase and inflammatory factors in the supernatant and the accumulation of autophagic vacuoles verified that the AP mouse cell model was established.The downregulation of LAMP2 and upregulation of LC3-II/I and SQSTM1 demonstrated that autophagy was impaired in AP.The expression of ZKSCAN3 was upregulated in AP.Inhibition of ZKSCAN3 increased the expression of LAMP2 and decreased the expression of the inflammatory factors,LC3-II/I and SQSTM1.Furthermore,ALKBH5 was upregulated in AP.Knockdown of ALKBH5 downregulated ZKSCAN3 expression and restored decreased autophagic flux in AP.Notably,the bioinformatic analysis revealed 23 potential m6A modification sites on ZKSCAN3 mRNA.The m6A modification of ZKSCAN3 mRNA was significantly decreased in AP.Knockdown of ALKBH5 increased the modification of ZKSCAN3 mRNA,which confirmed that ALKBH5 upregulated ZKSCAN3 expression in a m6A-dependent manner.CONCLUSION ALKBH5 inhibits autophagic flux through m6A demethylation of ZKSCAN3 mRNA in AP,thereby aggravating the severity of the disease.