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.

Sequential blood purification therapy for critical patients with hyperlipidemic severe acute pancreatitis

AIM: To evaluate the efficacy of sequential blood purification therapy in the treatment of critical patients with hyperlipidemic severe acute pancreatitis.METHODS: Thirty-one intensive care unit(ICU) patients with hyperlipidemic severe acute pancreatitis treated at the Second Affiliated Hospital of Harbin Medical University were divided into either a study group(n = 15; July 1, 2012 to June 30, 2014) or a control group(n = 16; July 1, 2010 to June 30, 2012) based on the implementation of sequential blood purification therapy. The control group received continuous venous-venous hemofiltration(CVVH) on the basis of conventional treatments, and the therapeutic dose of CVVH was 30 m L/kg per hour. The study group received sequential plasma exchange and CVVH on the basis of conventional treatments. The anticoagulation regimen of CVVH is the regional citrate anticoagulation. Mortality rate on day 28, rates of systemic and local complications, duration of ICU, and time to target serum lipid level, as well as physiologic and laboratory indices were compared between the two groups.RESULTS: The mortality rate on day 28 was significantly lower in the study group than in the control group(13.33% vs 37.50%; P < 0.05). The duration of ICU stay was significantly shorter in the study group than in the control group(7.4 ± 1.35 d vs 9.19 ± 2.99 d, P < 0.05). The time to target serum lipid level was significantly shorter in the study group than in the control group(3.47 ± 0.52 d vs 7.90 ± 1.14 d, P < 0.01). There were no significant differences in the rates of systemic complications and local complications between the two groups(60% vs 50% and 80% vs 81%, respectively). In the comparisons of physiologic and laboratory indices, serum albumin and C-reactive protein were significantly better in the study group than in the control group after treatment(37.8 ± 4.6 g/L vs 38.9 ± 5.7 g/L, and 20.5 ± 6.4 mg/L vs 28.5 ± 7.1 mg/L, respectively, both P < 0.05). With the exception of plateletcrit, no other indices showed significant differences between the two groups.CONCLUSION: Sequential blood purification therapy is effective in the treatment of ICU patients with hyperlipidemic severe acute pancreatitis and can improve patient prognosis.

Acute pancreatitis in the critical care setting:A review of assessment and intervention strategies

The incidence of acute pancreatitis(AP),a condition characterized by inflammation in the pancreas,has been increasing globally and is associated with several complications.This review elaborated on the etiology,clinical presentation,severity assessment,and treatment modalities of AP,mainly in the critical care setting.Patients with severe AP,as indicated by organ failure(>48 hours from onset),warrant treatment in the intensive care unit setting.The most common etiologies,biliary disease and alcohol consumption,and the advanced diagnostic tools used for the identification of the cause are highlighted.Different severity assessment tools are utilized for grading the severity of the disease,predicting patient outcomes,determining the associated risk,and guiding treatment decisions.The treatment interventions comprise various approaches,such as anti-infective therapy enteral nutrition,analgesics for pain,or minimally invasive surgical procedures,thereby demonstrating an evolving landscape of AP management.Furthermore,various complications such as necrosis,organ failure,and hemorrhage,necessitate disease monitoring and differential diagnosis and are crucial for optimal management of patients.Novel treatment modalities and advancements in multidisciplinary care emphasize the potential for reducing the burden of AP in critical care settings.

Association between acute peripancreatic fluid collections and early readmission in acute pancreatitis:A propensity-matched analysis

BACKGROUND Patients with acute pancreatitis(AP)frequently experience hospital readmissions,posing a significant burden to healthcare systems.Acute peripancreatic fluid collection(APFC)may negatively impact the clinical course of AP.It could worsen symptoms and potentially lead to additional complications.However,clinical evidence regarding the specific association between APFC and early readmission in AP remains scarce.Understanding the link between APFC and readmission may help improve clinical care for AP patients and reduce healthcare costs.AIM To evaluate the association between APFC and 30-day readmission in patients with AP.METHODS This retrospective cohort study is based on the Nationwide Readmission Database for 2016-2019.Patients with a primary diagnosis of AP were identified.Participants were categorized into those with and without APFC.A 1:1 propensity score matching for age,gender,and Elixhauser comorbidities was performed.The primary outcome was early readmission rates.Secondary outcomes included the incidence of inpatient complications and healthcare utilization.Unadjusted analyses used Mann-Whitney U andχ2 tests,while Cox regression models assessed 30-day readmission risks and reported them as adjusted hazard ratios(aHR).Kaplan-Meier curves and log-rank tests verified readmission risks.RESULTS A total of 673059 patients with the principal diagnosis of AP were included.Of these,5.1%had APFC on initial admission.After propensity score matching,each cohort consisted of 33914 patients.Those with APFC showed a higher incidence of inpatient complications,including septic shock(3.1%vs 1.3%,P<0.001),portal venous thrombosis(4.4%vs 0.8%,P<0.001),and mechanical ventilation(1.8%vs 0.9%,P<0.001).The length of stay(LOS)was longer for APFC patients[4(3-7)vs 3(2-5)days,P<0.001],as were hospital charges($29451 vs$24418,P<0.001).For 30-day readmissions,APFC patients had a higher rate(15.7%vs 6.5%,P<0.001)and a longer median readmission LOS(4 vs 3 days,P<0.001).The APFC group also had higher readmission charges($28282 vs$22865,P<0.001).The presence of APFC increased the risk of readmission twofold(aHR 2.52,95%confidence interval:2.40-2.65,P<0.001).The independent risk factors for 30-day readmission included female gender,Elixhauser Comorbidity Index≥3,chronic pulmonary diseases,chronic renal disease,protein-calorie malnutrition,substance use disorder,depression,portal and splenic venous thrombosis,and certain endoscopic procedures.CONCLUSION Developing APFC during index hospitalization for AP is linked to higher readmission rates,more inpatient complications,longer LOS,and increased healthcare costs.Knowing predictors of readmission can help target high-risk patients,reducing healthcare burdens.

Administration Rule of Hyperlipidemic Acute Pancreatitis Based on Data Mining

Objective:To excavate the medical pattern of hyperlipidemic acute pancreatitis based on Chinese Medicine Inheritance Assistant Platform software,hope to offer ideas for the treatment of the disease.Methods:Inpatient cases admitted to the Department of Gastroenterology of Shenzhen Hospital of Traditional Chinese Medicine for HLAP from September 2013 to June 2020 were collected,information on evidence patterns and formulations was extracted,an Excel database was established and professional terms were standardized,and data mining methods such as association rules and entropy clustering of complex systems were used to analyze medical patterns.Results:The main symbols of HLAP include abdominal pain,abdominal distinction,vomiting,fever,etc.The common used drags include Immature Orange Fruit,Baical Skullcap Root,Rhubarb and Chinese Thorowax Root,etc.The main drug pairs based on association rule analysis are"Baical Skullcap Root,Immature Orange Fruit","Rhubarb,Immature Orange Fruit","Baical Skullcap Root,Rhubarb,Immature Orange Fruit",etc,and 14 drug core combinations and 7 new formulations were extracted.Conclusion:The main synthesis of HLAP are solid-heat knots in the internal organs and dam-heat in the liver and gallbladder,and the formula is based on Da-chai-hu Decoction,the clinical treatment is based on attacking stagnation,activating blood circulation and removing dampness,which can offer reference for the clinical treatment of the disease.

Impact of cigarette smoking on recurrence of hyperlipidemic acute pancreatitis

AIM To investigate the impact of cigarette smoking on the recurrence rate and recurrence-free survival in patients with hyperlipidemic acute pancreatitis(HLAP).METHODS A total of 863 patients were admitted to our hospital for acute pancreatitis(AP) from January 2013 to March2016, of whom 88 diagnosed with HLAP were enrolled in this retrospective study. Demographic data, medical history, previous episodes of pancreatitis, consumption of alcohol and cigarettes, as well as biochemical and hematological data were carefully recorded for univariate and multivariate analyses. During followup, the information on current smoking status and recurrent AP was gathered. Recurrence-free survival(RFS) was calculated using the Kaplan-Meier method, and the differences between groups were compared using the log-rank test.RESULTS No significant differences were observed between the three groups in age or medical history of hyperlipidemia, fatty liver, diabetes mellitus, hypertension, or AP. The current smokers had a remarkably higher recurrence rate and a greater incidence of repeated episodes of AP(50.0% and 77.8%, respectively) than non-smokers(9.8% and 39.0%), and these two percentages were reduced to 9.1% and 36.4% for patients who gave up smoking. The median follow-up time was 13.5 mo and HLAP recurred after hospital discharge in 23(26.1%) patients. Multivariate analysis identified current smoking(HR = 6.3, P = 0.020) as an independent risk factor contributing to HLAP recurrence. Current smokers had significantly worse RFS than non-smokers(23 mo vs 42 mo), but no significant difference was documented between ex-smokers(34 mo) and non-smokers. The RFS was not significantly different between light and heavy smokers.CONCLUSION Smoking is associated with worse RFS and an increased rate of HLAP recurrence. Continued smoking correlates with a compromised survival and smoking cessation should be recommended.

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.

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.

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.

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.

Anemarsaponin B mitigates acute pancreatitis damage in mice through apoptosis reduction and MAPK pathway modulation

Background:Acute pancreatitis(AP),known for its rapid onset and significant incidence and mortality rates,presents a clinical challenge due to the limited availability of effective treatments and preventive measures.Anemarsaponin B(ASB)has emerged as a potential therapeutic agent,demonstrating capabilities in reducing immune inflammation,positioning it as a promising candidate for AP treatment.Methods:We investigated the effects of ASB on AP in mice,induced by caerulein and lipopolysaccharide(LPS).Peripheral blood samples were collected 24 h post-induction with caerulein to assess of key biomarkers including lipase,amylase,TNF-α,IL-1β,IL-6,SOD,and GSH-Px.A range of techniques such as immunohistochemistry staining,immunofluorescence staining,Western blotting,and quantitative Polymerase Chain Reaction(q-PCR),were employed to measure the expression of critical genes.Additionally,pancreas samples from the mice were harvested for microbiome and metabolome sequencing,with the data analyzed to understand the impact of ASB on AP.Results:Our study revealed that,compared to the sham group,the AP group exhibited significantly higher serum levels of lipase,amylase,and cytokines,while levels of SOD and GSH Px were notably lower.Treatment with ASB led to a substantial decrease in the levels of lipase,amylase,and cytokines,and an increase in SOD and GSH-Px levels.q-PCR analysis of pancreatic histiocytes corroborated these serum findings.Hematoxylin and Eosin(H&E)staining indicated significant alterations in the pathological changes in the pancreas,lungs,and small intestine of the AP model due to ASB.Immunofluorescence assays demonstrated that ASB alleviated the apoptosis of pancreatic histiocytes in the AP model.Western Blot and histological analyses showed that ASB reduced the phosphorylation of TAK,p38,JNK,and ERK proteins,as well as the levels of TRAF6 protein in the AP model.Furthermore,metabolomic and gut microbiota analysis identified 27 differential metabolites and 34 differential species.The combined metabolome and microbiome analysis suggested an association between certain microbes(e.g.,unclassified-Saprospiraceae and unclassified-Micavibrionales)and metabolites(e.g.,LysoPE(0:0/20:0),PC(DiMe(13,5)/PGJ2)),and Heptanoic acid,indicating potential pathways through which ASB may exert its therapeutic effects in AP.Conclusions:ASB exhibits therapeutic efficacy in treating AP induced by caerulein combined with lipopolysaccharide(LPS),primarily through modulating the mitogenactivated protein kinase(MAPK)signaling pathway.This discovery offers fresh perspectives for AP drug development,underscoring the potential of targeting specific cellular pathways.Additionally,the intricate interplay observed between the gut microbiota and metabolites following ASB treatment highlights novel therapeutic targets,suggesting that manipulating the gut microbiome and metabolome could be a viable strategy in AP management.These findings pave the way for further research into comprehensive treatment approaches that incorporate both pharmacological intervention and microbiota modulation.

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.

Early selective enteral feeding in treatment of acute pancreatitis: A case report

BACKGROUND Early initiation of enteral feeding is recognized to play a crucial role in improving the outcomes of treatment of acute pancreatitis.However,the method of adminis-tration of enteral nutrition remains debatable.We present the experience of treating a patient with moderate-severe acute pancreatitis,at high risk of progressing to a severe or fatal condition,using a novel method of selective feeding with duodenal isolation.CASE SUMMARY A 27-year-old female patient presented to the emergency unit of the hospital with a typical manifestation of acute pancreatitis.Despite a conventional treatment,the patient’s condition deteriorated by day 2 of hospitalization.Using an endoscopic approach,a novel catheter PandiCathffwas placed to the duodenum of the patient,isolating its segment between the duodenal bulb and the ligament of Treitz.In the isolated area created,a negative pressure was applied,followed by introduction of early selective enteral feeding.The patient’s condition subsequently improved in a rapid manner,and no complications often associated with moderate-to-severe acute pancreatitis developed.CONCLUSION Within 48 h of starting treatment with the novel method,it can prevent the development of multiple organ failure and,when combined with minimally invasive drainage methods,help prevent infection.