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.

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.

Clinical study of neutrophil-to-lymphocyte ratio and platelet-tolymphocyte ratio in hypertriglyceridemia-induced acute pancreatitis and acute biliary pancreatitis with persistent organ failure

BACKGROUND The neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)are novel inflammatory indicators that can be used to predict the severity and prognosis of various diseases.We categorize acute pancreatitis by etiology into acute biliary pancreatitis(ABP)and hypertriglyceridemia-induced acute pancreatitis(HTGP).AIM To investigate the clinical significance of NLR and PLR in assessing persistent organ failure(POF)in HTGP and ABP.METHODS A total of 1450 patients diagnosed with acute pancreatitis(AP)for the first time at Shanxi Bethune Hospital between January 2012 and January 2023 were enrolled.The patients were categorized into two groups according to the etiology of AP:ABP in 530 patients and HTGP in 241 patients.We collected and compared the clinical data of the patients,including NLR,PLR,and AP prognostic scoring systems,within 48 h of hospital admission.RESULTS The NLR(9.1 vs 6.9,P<0.001)and PLR(203.1 vs 160.5,P<0.001)were significantly higher in the ABP group than in the HTGP group.In the HTGP group,both NLR and PLR were significantly increased in patients with severe AP and those with a SOFA score≥3.Likewise,in the ABP group,NLR and PLR were significantly elevated in patients with severe AP,modified computed tomography severity index score≥4,Japanese Severity Score≥3,and modified Marshall score≥2.Moreover,NLR and PLR showed predictive value for the development of POF in both the ABP and HTGP groups.CONCLUSION NLR and PLR vary between ABP and HTGP,are strongly associated with AP prognostic scoring systems,and have predictive potential for the occurrence of POF in both ABP and HTGP.

Splenic Vein Thrombosis as a Complication of Hypertriglyceridemia-Induced Acute Pancreatitis

Background: Acute pancreatitis (AP) is an extensive inflammation condition that may lead to local and systemic complications, ranging from mild edematous peripancreatic fluid collection to multiorgan failure and death. Aim: To report the case of the patient with the complications that happened and the presented management. Case presentation: A 37-year-old female patient presented with acute necrotizing pancreatitis secondary to hypertriglyceridemia. During hospitalization, the patient developed severe ileus with splenic vein thrombosis. She was treated conservatively with Intravenous (IV) fluids, insulin infusion, anticoagulant, pain relief medication and antibiotics. Discussion: This case of pancreatitis induced splenic vein thrombosis (PIVST) was treated supportively with outstanding improvement of the patient’s symptoms. Conclusion: Acute pancreatitis can be complicated by splenic vein thrombosis that can be self-limited and treated with conservative measures.

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.

Hypertriglyceridemia-induced acute pancreatitis:a systematic review of the literature

Objective: To summarize the current evidence about the hypertriglyceridemia–induced acute pancreatitis (HAP). <br> Methods: Systematic review of the English language literature was conducted using PubMed/Medline database from its inception until August 2016. As a searching methodology, we have used a combination of ‘acute pancreatitis' and ‘hypertriglyceridemia' as keywords into the title. <br> Results: The diagnosis ofHAP should be based on two out of the three criteria recommended by the international guidelines: characteristic clinical picture, serum pancreatic enzymes, and appropriate imagistics. The diagnosis ofHAPshould be distinguished between mild hypertriglyceridemia (> 150 mg/dL), which accompanies around one-third of all-causes acute pancreatitis, and severe hypertriglyceridemia (> 1 000 mg/dL) which generates acute pancreatitis. There is mixed evidence regarding a worse prognosis for patients withHAP, and a clear conclusion cannot be drawn. Similar to all the other etiologies, inHAP the initial treatment efforts should be nonspecific and addressed to acute pancreatitis, while pharmacologic and mechanical techniques should be added to lower the serum triglycerides as soon as possible. <br> Conclusions: We may conclude thatHAP should be managed to respect all the general principles, also adding all the available resources to lower the serum triglycerides value, as early as possible in the acute setting and on long-term to prevent recurrences.

Clinical effects of phospholipase D2 in attenuating acute pancreatitis

BACKGROUND The objective of the current study was to elucidate the clinical mechanism through which phospholipase D2(PLD2)exerted a regulatory effect on neutrophil migra-tion,thereby alleviating the progression of acute pancreatitis.AIM To elucidate the clinical mechanism through which PLD2 exerted a regulatory effect on neutrophil migration,thereby alleviating the progression of acute pan-creatitis.METHODS The study involved 90 patients diagnosed with acute pancreatitis,admitted to our hospital between March 2020 and November 2022.A retrospective analysis was conducted,categorizing patients based on Ranson score severity into mild(n=25),moderate(n=30),and severe(n=35)groups.Relevant data was collected for each group.Western blot analysis assessed PLD2 protein expression in patient serum.Real-time reverse transcription polymerase chain reaction was used to evaluate the mRNA expression of chemokine receptors associated with neutrophil migration.Serum levels of inflammatory factors in patients were detected using enzyme-linked immunosorbent assay.Transwell migration tests were conducted to compare migration of neutrophils across groups and analyze the influence of PLD2 on neutrophil migration.RESULTS Overall data analysis did not find significant differences between patient groups(P>0.05).The expression of PLD2 protein in the severe group was lower than that in the moderate and mild groups(P<0.05).The expression level of PLD2 in the moderate group was also lower than that in the mild group(P<0.05).The severity of acute pancreatitis is negatively correlated with PLD2 expression(r=-0.75,P=0.002).The mRNA levels of C-X-C chemokine receptor type 1,C-X-C chemokine receptor type 2,C-C chemokine receptor type 2,and C-C chemokine receptor type 5 in the severe group are significantly higher than those in the moderate and mild groups(P<0.05),and the expression levels in the moderate group are also higher than those in the mild group(P<0.05).The levels of C-reactive protein,tumor necrosis factor-α,interleukin-1β,and interleukin-6 in the severe group were higher than those in the moderate and mild groups(P<0.05),and the levels in the moderate group were also higher than those in the mild group(P<0.05).The number of migrating neutrophils in the severe group was higher than that in the moderate and mild groups(P<0.05),and the moderate group was also higher than the mild group(P<0.05).In addition,the number of migrating neutrophils in the mild group combined with PLD2 inhibitor was higher than that in the mild group(P<0.05),and the number of migrating neutrophils in the moderate group combined with PLD2 inhibitor was higher than that in the moderate group(P<0.05).The number of migrating neutrophils in the severe group+PLD2 inhibitor group was significantly higher than that in the severe group(P<0.05),indicating that PLD2 inhibitors significantly stimulated neutrophil migration.CONCLUSION PLD2 exerted a crucial regulatory role in the pathological progression of acute pancreatitis.Its protein expression varied among patients based on the severity of the disease,and a negative correlation existed between PLD2 expression and disease severity.Additionally,PLD2 appeared to impede acute pancreatitis progression by limiting neutrophil migration.

Transfer RNA-derived small RNA serves as potential non-invasive diagnostic marker and a novel therapeutic target for acute pancreatitis

Transfer RNA(tRNA)-derived fragments,a new type of tRNA-derived small RNA(tsRNA),can be cleaved from tRNA by enzymes to regulate target gene expression at the transcriptional and translational levels.tsRNAs are not only degradation fragments but also have biological functions,including those in immune inflammation,metabolic disorders,and cell death.tsRNA dysregulation is closely associated with multiple diseases,including various cancers and acute pancreatitis(AP).AP is a common gastrointestinal disease,and its incidence increases annually.AP development is associated with tsRNAs,which regulate cell injury and induce inflammation,especially pyroptosis and ferroptosis.Notably,serum tRF36 has the potential to serve as a non-invasive diagnostic biomarker and leads to pancreatic acinar cell ferroptosis causing inflammation to promote AP.We show the characteristics of tsRNAs and their diagnostic value and function in AP,and discuss the potential opportunities and challenges of using tsRNAs in clinical applications and research.

Maternal and fetal death associated with acute pancreatitis during pregnancy:A case report

BACKGROUND Acute pancreatitis in pregnancy is a rare but serious condition that can lead to high maternal mortality and fetal loss.Instances of pregnancy complicated by severe acute pancreatitis,particularly with subsequent respiratory and cardiac arrest,are rarely reported.CASE SUMMARY We present the case of a 35-year-old woman,at 36+5 weeks of gestation,who presented with paroxysmal epigastric pain accompanied by low back pain,nausea,and vomiting.According to the clinical symptoms,B-ultrasound imaging and biochemical indicators,the patient was diagnosed with acute pancreatitis and initially managed conservatively.However,3 hours after admission,the patient experienced respiratory and cardiac arrest,and the fetus died.In this case,the adverse outcomes occurred due to the lack of aggressive fluid resuscitation and an active surgical intervention.CONCLUSION Implementing aggressive fluid resuscitation to sustain tissue perfusion,alongside the proactive evaluation of pharmacological agents that suppress gastric acid secretion and inhibit pancreatic enzyme activity,may be beneficial in mitigating the risk of a severely adverse prognosis.Effective management of acute pancreatitis during pregnancy requires careful timing of surgical intervention,a thorough evaluation of the risks and benefits regarding the continuation or termination of pregnancy,and a focus on safeguarding both maternal and fetal health.

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.

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.

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.

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.

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.