Fasudil-modified macrophages reduce inflammation and regulate the immune response in experimental autoimmune encephalomyelitis

Multiple sclerosis is characterized by demyelination and neuronal loss caused by inflammatory cell activation and infiltration into the central nervous system.Macrophage polarization plays an important role in the pathogenesis of experimental autoimmune encephalomyelitis,a traditional experimental model of multiple sclerosis.This study investigated the effect of Fasudil on macrophages and examined the therapeutic potential of Fasudil-modified macrophages in experimental autoimmune encephalomyelitis.We found that Fasudil induced the conversion of macrophages from the pro-inflammatory M1 type to the anti-inflammatory M2 type,as shown by reduced expression of inducible nitric oxide synthase/nitric oxide,interleukin-12,and CD16/32 and increased expression of arginase-1,interleukin-10,CD14,and CD206,which was linked to inhibition of Rho kinase activity,decreased expression of toll-like receptors,nuclear factor-κB,and components of the mitogen-activated protein kinase signaling pathway,and generation of the pro-inflammatory cytokines tumor necrosis factor-α,interleukin-1β,and interleukin-6.Crucially,Fasudil-modified macrophages effectively decreased the impact of experimental autoimmune encephalomyelitis,resulting in later onset of disease,lower symptom scores,less weight loss,and reduced demyelination compared with unmodified macrophages.In addition,Fasudil-modified macrophages decreased interleukin-17 expression on CD4^(+)T cells and CD16/32,inducible nitric oxide synthase,and interleukin-12 expression on F4/80^(+)macrophages,as well as increasing interleukin-10 expression on CD4^(+)T cells and arginase-1,CD206,and interleukin-10 expression on F4/80^(+)macrophages,which improved immune regulation and reduced inflammation.These findings suggest that Fasudil-modified macrophages may help treat experimental autoimmune encephalomyelitis by inducing M2 macrophage polarization and inhibiting the inflammatory response,thereby providing new insight into cell immunotherapy for multiple sclerosis.

Clinical manifestations,diagnosis and long-term prognosis of adult autoimmune enteropathy:Experience from Peking Union Medical College Hospital

BACKGROUND Autoimmune enteropathy(AIE)is a rare disease whose diagnosis and long-term prognosis remain challenging,especially for adult AIE patients.AIM To improve overall understanding of this disease’s diagnosis and prognosis.METHODS We retrospectively analyzed the clinical,endoscopic and histopathological characteristics and prognoses of 16 adult AIE patients in our tertiary medical center between 2011 and 2023,whose diagnosis was based on the 2007 diagnostic criteria.RESULTS Diarrhea in AIE patients was characterized by secretory diarrhea.The common endoscopic manifestations were edema,villous blunting and mucosal hyperemia in the duodenum and ileum.Villous blunting(100%),deep crypt lymphocytic infiltration(67%),apoptotic bodies(50%),and mild intraepithelial lymphocytosis(69%)were observed in the duodenal biopsies.Moreover,there were other remarkable abnormalities,including reduced or absent goblet cells(duodenum 94%,ileum 62%),reduced or absent Paneth cells(duodenum 94%,ileum 69%)and neutrophil infiltration(duodenum 100%,ileum 69%).Our patients also fulfilled the 2018 diagnostic criteria but did not match the 2022 diagnostic criteria due to undetectable anti-enterocyte antibodies.All patients received glucocorticoid therapy as the initial medication,of which 14/16 patients achieved a clinical response in 5(IQR:3-20)days.Immunosuppressants were administered to 9 patients with indications of steroid dependence(6/9),steroid refractory status(2/9),or intensified maintenance medication(1/9).During the median of 20.5 months of followup,2 patients died from multiple organ failure,and 1 was diagnosed with non-Hodgkin’s lymphoma.The cumulative relapse-free survival rates were 62.5%,55.6%and 37.0%at 6 months,12 months and 48 months,respectively.CONCLUSION Certain histopathological findings,including a decrease or disappearance of goblet and Paneth cells in intestinal biopsies,might be potential diagnostic criteria for adult AIE.The long-term prognosis is still unsatisfactory despite corticosteroid and immunosuppressant medications,which highlights the need for early diagnosis and novel medications.

Diabetes mellitus in patients with type 1 autoimmune pancreatitis at diagnosis and after corticosteroid therapy

Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is observed.However,evidence on the circumstances under which corticosteroid therapy(CST)for AIP improves or worsens DM is scarce.This study aimed to demonstrate and identify predictors of DM control under the influence of CST.Methods:Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed:pre-existing DM(pDM),concurrent DM(cDM),and non-DM(nDM).The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as‘improvement’and‘non-improvement’(including‘no change’and‘exacerbation’).Results:Among 101 patients with type 1 AIP,52(51.5%)patients were complicated with DM at the time of AIP diagnosis,with 36 patients in the cDM group and 16 patients in the pDM group.The incidences of diffuse pancreatic swelling(72.2%)and pancreatic body/tail involvement(91.7%)were significantly higher in the cDM group than in both the pDM and nDM groups.Of the 52 patients with DM,CST was administered in 48 cases.Multivariate logistic analysis identified that elevated serum gamma-glutamyl transferase(GGT)level at AIP diagnosis[odds ratio(OR)=0.032,95%confidence interval(CI):0.003-0.412,P=0.008]and pancreatic atrophy after CST(OR=0.027,95%CI:0.003-0.295,P=0.003)were negatively associated with DM control improvement.Conclusions:Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP diagnosis.CST exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis,particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.

Autoimmune hepatitis and primary sclerosing cholangitis after direct-acting antiviral treatment for hepatitis C virus:A case report

BACKGROUND Chronic hepatitis C virus(HCV)infection is a major global health concern that leads to liver fibrosis,cirrhosis,and cancer.Regimens containing direct-acting antivirals(DAAs)have become the mainstay of HCV treatment,achieving a high sustained virological response(SVR)with minimal adverse events.CASE SUMMARY A 74-year-old woman with chronic HCV infection was treated with the DAAs ledipasvir,and sofosbuvir for 12 wk and achieved SVR.Twenty-four weeks after treatment completion,the liver enzyme and serum IgG levels increased,and antinuclear antibody became positive without HCV viremia,suggesting the development of autoimmune hepatitis(AIH).After liver biopsy indicated AIH,a definite AIH diagnosis was made and prednisolone was initiated.The treatment was effective,and the liver enzyme and serum IgG levels normalized.However,multiple strictures of the intrahepatic and extrahepatic bile ducts with dilatation of the peripheral bile ducts appeared on magnetic resonance cholangiopancreatography after 3 years of achieving SVR,which were consistent with primary sclerosing cholangitis.CONCLUSION The potential risk of developing autoimmune liver diseases after DAA treatment should be considered.

Autoimmune pancreatitis:Cornerstones and future perspectives

Autoimmune pancreatitis(AIP)is an autoimmune subtype of chronic pancreatitis resulting from the aberrant immune response against the pancreas,leading to inflammation and fibrosis.Although AIP is rare,its incidence is increasing and is often misdiagnosed as other pancreatic diseases.AIP is commonly classified into two types.Type 1 AIP(AIP-1)is typically associated with elevated serum immunoglobulin G4(IgG4)levels and systemic manifestations,while type 2 AIP is typically a more localized form of the disease,and may coexist with other autoimmune disorders,especially inflammatory bowel diseases.Additionally,there is emerging recognition of a third type(type 3 AIP),which refers to immunotherapy-triggered AIP,although this classification is still gaining acceptance in medical literature.The clinical manifestations of AIP mainly include painless jaundice and weight loss.Elevated serum IgG4 levels are particularly characteristic of AIP-1.Diagnosis relies on a combination of clinical,laboratory,radiological,and histological findings,given the similarity of AIP symptoms to other pancreatic disorders.The mainstay of treatment for AIP is steroid therapy,which is effective in most cases.Severe cases might require additional imm-unosuppressive agents.This review aims to summarize the current knowledge of AIP,encompassing its epidemiology,etiology,clinical presentation,diagnosis,and treatment options.We also address the challenges and controversies in diagnosing and treating AIP,such as distinguishing it from pancreatic cancer and managing long-term treatment,highlighting the need for increased awareness and knowledge of this complex disease.

Anti-N-methyl-D-aspartate receptor type autoimmune encephalitis with severe pneumonia:a case report

Autoimmune encephalitis(AE)is a type of encephalitis caused by autoimmune disease.AE was included on a list of the first batch of 121 rare diseases published by the Chinese National Health Commission on 11^(th)May 2018.Currently,patients with AE account for 10%-20% of encephalitis cases,with 54%-80% of those cases classified as the anti-N-methyl-D-aspartate receptor(NMDAR)type,which is the most common type.[1]In 2010,China reported the first case of a patient withanti-NMDARtype AE.

Association of autoimmune thyroid disease with type 1 diabetes mellitus and its ultrasonic diagnosis and management

As a common hyperglycemic disease,type 1 diabetes mellitus(T1DM)is a complicated disorder that requires a lifelong insulin supply due to the immunemediated destruction of pancreaticβcells.Although it is an organ-specific autoimmune disorder,T1DM is often associated with multiple other autoimmune disorders.The most prevalent concomitant autoimmune disorder occurring in T1DM is autoimmune thyroid disease(AITD),which mainly exhibits two extremes of phenotypes:hyperthyroidism[Graves'disease(GD)]and hypothyroidism[Hashimoto's thyroiditis,(HT)].However,the presence of comorbid AITD may negatively affect metabolic management in T1DM patients and thereby may increase the risk for potential diabetes-related complications.Thus,routine screening of thyroid function has been recommended when T1DM is diagnosed.Here,first,we summarize current knowledge regarding the etiology and pathogenesis mechanisms of both diseases.Subsequently,an updated review of the association between T1DM and AITD is offered.Finally,we provide a relatively detailed review focusing on the application of thyroid ultrasonography in diagnosing and managing HT and GD,suggesting its critical role in the timely and accurate diagnosis of AITD in T1DM.

The anti-inflammatory effects of exercise on autoimmune diseases:A 20-year systematic review

Background:The anti-inflammatory effect of exercise may be an underlying factor in improving several autoimmune diseases.The aim of this systematic review was to examine the evidence on the role of exercise training in mitigating inflammation in adolescents and adults with autoimmune disease.Methods:PubMed,Web of Science,and Embase databases were systematically reviewed for related studies published between January 1,2003,and August 31,2023.All randomized and non-randomized controlled trials of exercise interventions with autoimmune disease study participants that evaluated inflammation-related biomarkers were included.The quality of evidence was assessed using the Tool for the assEssment of Study qualiTy and reporting in EXercise scale and Cochrane bias risk tool.Results:A total of 14,565 records were identified.After screening the titles,abstracts,and full texts,87 were eligible for the systematic review.These studies were conducted in 25 different countries and included a total of 2779 participants(patients with autoimmune disease,in exercise or control groups).Overall,the evidence suggests that inflammation-related markers such as C-reactive protein,interleukin 6,and tumor necrosis factor a were reduced by regular exercise interventions.Regular exercise interventions combined with multiple exercise modes were associated with greater benefits.Conclusion:Regular exercise training by patients with autoimmune disease exerts an anti-inflammatory influence.This systematic review provides support for the promotion and development of clinical exercise intervention programs for patients with autoimmune disease.Most patients with autoimmune disease can safely adopt moderate exercise training protocols,but changes in inflammation biomarkers will be modest at best.Acute exercise interventions are ineffective or even modestly but transiently pro-inflammatory.

Autoimmune hepatitis-primary biliary cholangitis overlap syndrome complicated by various autoimmune diseases:A case report

BACKGROUND Autoimmune hepatitis(AIH)and primary biliary cholangitis(PBC)are two common clinical autoimmune liver diseases,and some patients have both diseases;this feature is called AIH-PBC overlap syndrome.Autoimmune thyroid disease(AITD)is the most frequently overlapping extrahepatic autoimmune disease.Immunoglobulin(IgG)4-related disease is an autoimmune disease recognized in recent years,characterized by elevated serum IgG4 levels and infiltration of IgG4-positive plasma cells in tissues.CASE SUMMARY A 68-year-old female patient was admitted with a history of right upper quadrant pain,anorexia,and jaundice on physical examination.Laboratory examination revealed elevated liver enzymes,multiple positive autoantibodies associated with liver and thyroid disease,and imaging and biopsy suggestive of pancreatitis,hepatitis,and PBC.A diagnosis was made of a rare and complex overlap syndrome of AIH,PBC,AITD,and IgG4-related disease.Laboratory features improved on treatment with ursodeoxycholic acid,methylprednisolone,and azathioprine.CONCLUSION This case highlights the importance of screening patients with autoimmune diseases for related conditions.

Can serum immunoglobulin G4 levels and age serve as reliable predictors of relapse in autoimmune pancreatitis?

We are writing in response to the paper published in the World Journal of Gastroenterology by Zhou et al.The authors identified higher serum immunoglobulin(Ig)G4 levels and age over 55 years as independent risk factors for disease relapse.Despite notable strengths,it is crucial to address potential biases.Firstly,the cohort study included 189 patients with autoimmune pancreatitis(AIP)type 1(with higher IgG4 seropositivity and higher relapse)and 24 with type 2(with lower IgG4 seropositivity and lower relapse).Consequently,most,if not all,AIP type 2 patients were assigned to the normal group,possibly inflating the association of higher serum IgG4 levels with relapse and potentially exaggerating the association of older age with relapse.Secondly,the authors did not provide sufficient details regarding AIP diagnosis,such as the ratio of definitive vs probable cases and the proportion of biopsies.In cases where histological evidence is unavailable or indeterminate,AIP type 2 may be misdiagnosed as definitive type 1,and type 1 may also be misdiagnosed as probable type 2,particularly in cases with normal or mildly elevated serum IgG4 levels.Lastly,in this retrospective study,approximately one-third of the consecutive patients initially collected were excluded for various reasons.Accordingly,the impact of nonrandom exclusion on relapse outcomes should be carefully considered.In conclusion,the paper by Zhou et al offers plausible,though not entirely compelling,evidence suggesting a predictive role of elevated serum IgG4 levels and advanced age in AIP relapse.The foundation for future investigations lies in ensuring a reliable diagnosis and accurate disease subtyping,heavily dependent on obtaining histological specimens.In this regard,endoscopic ultrasound-guided fine-needle biopsy emerges as a pivotal component of the diagnostic process,contributing to mitigating biases in future explorations of the disease.

Trends of autoimmune liver disease inpatient hospitalization and mortality from 2011 to 2017:A United States nationwide analysis

BACKGROUND Autoimmune liver diseases(AiLD)encompass a variety of disorders that target either the liver cells(autoimmune hepatitis,AIH)or the bile ducts[primary biliary cholangitis(PBC),and primary sclerosing cholangitis(PSC)].These conditions can progress to chronic liver disease(CLD),which is characterized by fibrosis,cirrhosis,and hepatocellular carcinoma.Recent studies have indicated a rise in hospitalizations and associated costs for CLD in the US,but information regarding inpatient admissions specifically for AiLD remains limited.AIM To examine the trends and mortality of inpatient hospitalization of AiLD from 2011 to 2017.METHODS This study is a retrospective analysis utilizing the National Inpatient Sample(NIS)databases.All subjects admitted between 2011 and 2017 with a diagnosis of AiLD(AIH,PBC,PSC)were identified using the International Classification of Diseases(ICD-9)and ICD-10 codes.primary AiLD admission was defined if the first admission code was one of the AiLD codes.secondary AiLD admission was defined as having the AiLD diagnosis anywhere in the admission diagnosis(25 diagnoses).Subjects aged 21 years and older were included.The national estimates of hospitalization were derived using sample weights provided by NIS.χ^(2)tests for categorical data were used.The primary trend characteristics were in-hospital mortality,hospital charges,and length of stay.RESULTS From 2011 to 2017,hospitalization rates witnessed a significant decline,dropping from 83263 admissions to 74850 admissions(P<0.05).The patients hospitalized were predominantly elderly(median 53%for age>65),mostly female(median 59%)(P<0.05),and primarily Caucasians(median 68%)(P<0.05).Medicare was the major insurance(median 56%),followed by private payer(median 27%)(P<0.05).The South was the top geographical distribution for these admissions(median 33%)(P<0.05),with most admissions taking place in big teaching institutions(median 63%)(P<0.05).Total charges for admissions rose from 66031 in 2011 to 78987 in 2017(P<0.05),while the inpatient mortality rate had a median of 4.9%(P<0.05),rising from 4.67%in 2011 to 5.43%in 2017.The median length of stay remained relatively stable,changing from 6.94 days(SD=0.07)in 2011 to 6.51 days(SD=0.06)in 2017(P<0.05).Acute renal failure emerged as the most common risk factor associated with an increased death rate,affecting nearly 68%of patients(P<0.05).CONCLUSION AiLD-inpatient hospitalization showed a decrease in overall trends over the studied years,however there is a significant increase in financial burden on healthcare with increasing in-hospital costs along with increase in mortality of hospitalized patient with AiLD.

Management of autoimmune hepatitis induced by hepatitis delta virus

Approximately 12-72 million people worldwide are co-infected with hepatitis B virus(HBV)and hepatitis delta virus(HDV).This concurrent infection can lead to several severe outcomes with hepatic disease,such as cirrhosis,fulminant hepatitis,and hepatocellular carcinoma,being the most common.Over the past few decades,a correlation between viral hepatitis and autoimmune diseases has been reported.Furthermore,autoantibodies have been detected in the serum of patients co-infected with HBV/HDV,and autoimmune features have been reported.However,to date,very few cases of clinically significant autoimmune hepatitis(AIH)have been reported in patients with HDV infection,mainly in those who have received treatment with pegylated interferon.Interestingly,there are some patients with HBV infection and AIH in whom HDV infection is unearthed after receiving treatment with immunosuppressants.Consequently,several questions remain unanswered with the challenge to distinguish whether it is autoimmune or“autoimmune-like”hepatitis being the most crucial.Second,it remains uncertain whether autoimmunity is induced by HBV or delta virus.Finally,we investigated whether the cause of AIH lies in the previous treatment of HDV with pegylated interferon.These pressing issues should be elucidated to clarify whether new antiviral treatments for HDV,such as Bulevirtide or immu-nosuppressive drugs,are more appropriate for the management of patients with HDV and AIH.

Knockout of C6orf120 in Rats Alleviates Concanavalin A-induced Autoimmune Hepatitis by Regulating Macrophage Polarization

Objective The effect of the functionally unknown gene C6orf120 on autoimmune hepatitis was investigated on C6orf120 knockout rats(C6orf120^(-/-))and THP-1 cells.Method Six–eight-week-old C6orf120^(-/-)and wild-type(WT)SD rats were injected with Con A(16 mg/kg),and euthanized after 24 h.The sera,livers,and spleens were collected.THP-1 cells and the recombinant protein(rC6ORF120)were used to explore the mechanism in vitro.The frequency of M1 and M2 macrophages was analyzed using flow cytometry.Western blotting and PCR were used to detect macrophage polarization-associated factors.Results C6orf120 knockout attenuated Con A-induced autoimmune hepatitis.Flow cytometry indicated that the proportion of CD68^(+)CD86^(+)M1 macrophages from the liver and spleen in the C6orf120^(-/-)rats decreased.C6orf120 knockout induced downregulation of CD86 protein and the mRNA levels of related inflammatory factors TNF-α,IL-1β,and IL-6 in the liver.C6orf120 knockout did not affect the polarization of THP-1 cells.However,rC6ORF120 promoted the THP-1 cells toward CD68^(+)CD80^(+)M1 macrophages and inhibited the CD68^(+)CD206^(+)M2 phenotype.Conclusion C6orf120 knockout alleviates Con A-induced autoimmune hepatitis by inhibiting macrophage polarization toward M1 macrophages and reducing the expression of related inflammatory factors in C6orf120^(-/-)rats.

Unmet needs in biomarkers for autoimmune pancreatitis diagnosis

Autoimmune pancreatitis(AIP)is a rare chronic autoimmune disorder.The diagnosis of AIP mainly depends on histopathology,imaging and response to treatment.Serum immunoglobulin 4(IgG4)is used only as collateral evidence in diagnostic criteria for AIP because of its moderate sensitivity.Serum IgG4 levels are normal in 15%-37%of type 1 AIP and most of type 2 AIP patients.In these patients,the indeterminate imaging and histopathology may lead to the difficulty in definitive diagnosis of AIP.Therefore,discovery of new biomarkers is impor-tant for AIP diagnosis.Here,we provide some views on the progression and challenges in identifying novel serological biomarkers in AIP diagnosis.

Understanding autoimmune pancreatitis: Clinical features, management challenges, and association with malignancies

In this editorial we comment on the article by Jaber et al.Autoimmune pancreatitis(AIP)represents a distinct form of pancreatitis,categorized into AIP-1 and AIP-2,characterized by obstructive jaundice,lymphoplasmacytic infiltrate,and fibrosis.AIP-1,associated with elevated immunoglobulin G4(IgG4)levels,exhibits higher relapse rates,affecting older males,while AIP-2 is less common and linked to inflammatory bowel disease.AIP is considered a manifestation of IgG4-related systemic disease,sharing characteristic histological findings.Steroids are the primary treatment,with emerging biomarkers like interferon alpha and inter-leukin-33.AIP poses an increased risk of various malignancies,and the assoc-iation with pancreatic cancer is debated.Surgery is reserved for severe cases,necessitating careful evaluation due to diagnostic challenges.AIP patients may have concurrent PanINs but display favorable long-term outcomes compared to pancreatic cancer patients.Thorough diagnostic assessment,including biopsy and steroid response,is crucial for informed surgical decisions in AIP.

Advancements in autoimmune hepatitis management:Perspectives for future guidelines

The first-line treatment for autoimmune hepatitis involves the use of prednisone or prednisolone either as monotherapy or in combination with azathioprine(AZA).Budesonide has shown promise in inducing a complete biochemical response(CBR)with fewer adverse effects and is considered an optional first-line treatment,particularly for patients without cirrhosis;however,it is worth noting that the design of that study favored budesonide.A recent real-life study revealed higher CBR rates with prednisone when equivalent initial doses were administered.Current guidelines recommend mycophenolate mofetil(MMF)for patients who are intolerant to AZA.It is important to mention that the evidence supporting this recommendation is weak,primarily consisting of case series.Nevertheless,MMF has demonstrated superiority to AZA in the context of renal transplant.Recent comparative studies have shown higher CBR rates,lower therapeutic failure rates,and reduced intolerance in the MMF group.These findings may influence future guidelines,potentially leading to a significant modification in the first-line treatment of autoimmune hepatitis.Until recently,the only alternative to corticosteroids was lifelong maintenance treatment with AZA,which comes with notable risks,such as skin cancer and lymphoma.Prospective trials are essential for a more comprehensive assessment of treatment suspension strategies,whether relying on histological criteria,strict biochemical criteria,or a combination of both.Single-center studies using chloroquine diphosphate have shown promising results in significantly reducing relapse rates compared to placebo.However,these interesting findings have yet to be replicated by other research groups.Additionally,second-line drugs,such as tacrolimus,rituximab,and infliximab,should be subjected to controlled trials for further evaluation.

The Value of Traditional Medicine Should not be Underestimated-Traditional Chinese Medicine in Treatment of Autoimmune Diseases

Autoimmune diseases of the nervous system(ADNS)are characterized by the formation of a pronounced neurologic deficit and often lead to disability.The attention of doctors and researchers is increasingly attracted by complementary medicine as adjuvant or preventive therapy for various diseases,including autoimmune diseases.Traditional Chinese medicine(TCM)is a combination of treatment methods that include acupuncture,herbal medicine,dietetics,physical exercises,and other methods that are often used in conjunction with recognized approaches of official medical science.The article describes the application of TCM techniques in autoimmune diseases of the nervous system,and demonstrates clinical experience in the use of acupuncture,herbal medicine,diets and physical exercises.Traditional and complementary medicine is an important and often underestimated healthcare resource,especially in the prevention and treatment of autoimmune diseases of the nervous system.

Fermented Lentinus edodes extract containingα-glucan ameliorates concanavalin A-induced autoimmune hepatitis in mice

Autoimmune hepatitis(AIH)is a chronic inflammatory liver disease that threatens human health worldwide.The aim of this study was to detect the protective effect of a fermented Lentinus edodes extract containingα-glucan(FLA),in a concanavalin A(Con A)-induced AIH mouse model and to determine the underlying liver-protective mechanism.The results showed that compared with the model group,the level of proinflammatory cytokines in serum of FLA pretreated mice was significantly decreased,and the degree of inflammatory cell infiltration in liver,thymus and spleen was significantly reduced.Quantitative polymerase chain reaction,immunohistochemistry,and Western blotting showed that FLA pre-treatment inhibited the Con A-induced apoptosis of hepatocytes by down-regulating the expression of BAX and up-regulating the expression of BCL-2.Further research found that FLA may improve liver injury in mice by activating NRF2 signaling pathway and inhibiting TRAF6/NF-κB signaling pathway.Thus,FLA may improve liver injury in mice by shifting gut microbial composition to reduce the release of inflammatory cytokines in the serum and prevent the necrosis of hepatocytes.Up-regulation of NRF2 signaling pathway,down-regulation of TRAF6/NF-κB signaling pathway,and an increase in the relative abundance of Lactobacillus_johnsonii and Ligilactobacillus_murinus play a protective role in liver.

Type one autoimmune pancreatitis based on clinical diagnosis: A case report

BACKGROUND Autoimmune pancreatitis(AIP)is a rare form of autoimmune-mediated pancrea-titis,which is easily misdiagnosed as pancreatic cancer and thus treated surgi-cally.We studied the diagnosis and treatment of a patient with type 1 AIP recent-ly admitted to our hospital,and reviewed the literature to provide a reference for clinical diagnosis of AIP.CASE SUMMARY The chief complaint was yellowing of the body,eyes and urine for 21 d.The pa-tient's clinical presentation was obstructive jaundice and imaging suggested pan-creatic swelling.It was difficult to distinguish between inflammation and tumor.Serum immunoglobulin G4(IgG4)was markedly elevated.IgG4 is an important serological marker for type 1 AIP.The patient was diagnosed with AIP,IgG4-related cholangitis,acute cholecystitis and hepatic impairment.After applying hormonal therapy,the patient's symptoms improved significantly.At the same time,imaging suggested that pancreatic swelling subsided,and liver function and other biochemical indicators decreased.The treatment was effective.CONCLUSION In patients with pancreatic swelling,the possibility of AIP should be considered.

Two-sample Mendelian randomization analysis of causal relationship between eczema and autoimmune diseases

Objective:The causal relationship between eczema and autoimmune diseases has not been previously reported.This study aims to evaluate the causal relationship between eczema and autoimmune diseases.Methods:The two‐sample Mendelian randomization(MR)method was used to assess the causal effect of eczema on autoimmune diseases.Summary data from the Genome-Wide Association Study Catalog(GWAS)were obtained from the Integrative Epidemiology Unit(IEU)database.For eczema and autoimmune diseases,genetic instrument variants(GIVs)were identified according to the significant difference(P<5×10−8).Causal effect estimates were generated using the inverse‐variance weighted(IVW)method.MR Egger,maximum likelihood,MR-PRESSO,and MR-RAPS methods were used for alternative analyses.Sensitivity tests,including heterogeneity,horizontal pleiotropy,and leave-one-out analyses,were performed.Finally,reverse causality was assessed.Results:Genetic susceptibility to eczema was associated with an increased risk of Crohn’s disease(OR=1.444,95%CI 1.199 to 1.738,P<0.001)and ulcerative colitis(OR=1.002,95%CI 1.001 to 1.003,P=0.002).However,no causal relationship was found for the other 6 autoimmune diseases,including systemic lupus erythematosus(SLE)(OR=0.932,P=0.401),bullous pemphigoid(BP)(OR=1.191,P=0.642),vitiligo(OR=1.000,P=0.327),multiple sclerosis(MS)(OR=1.000,P=0.965),ankylosing spondylitis(AS)(OR=1.001,P=0.121),rheumatoid arthritis(RA)(OR=1.000,P=0.460).Additionally,no reverse causal relationship was found between autoimmune diseases and eczema.Conclusion:Eczema is associated with an increased risk of Crohn’s disease and ulcerative colitis.No causal relationship is found between eczema and SLE,MS,AS,RA,BP,or vitiligo.