BACKGROUND Despite advances in research on psychopathology and social media use,no comprehensive review has examined published papers on this type of research and considered how it was affected by the coronavirus dise...BACKGROUND Despite advances in research on psychopathology and social media use,no comprehensive review has examined published papers on this type of research and considered how it was affected by the coronavirus disease 2019(COVID-19)outbreak.AIM To explore the status of research on psychopathology and social media use before and after the COVID-19 outbreak.METHODS We used Bibliometrix(an R software package)to conduct a scientometric analysis of 4588 relevant studies drawn from the Web of Science Core Collection,PubMed,and Scopus databases.RESULTS Such research output was scarce before COVID-19,but exploded after the pandemic with the publication of a number of high-impact articles.Key authors and institutions,located primarily in developed countries,maintained their core positions,largely uninfluenced by COVID-19;however,research production and collaboration in developing countries increased significantly after COVID-19.Through the analysis of keywords,we identified commonly used methods in this field,together with specific populations,psychopathological conditions,and clinical treatments.Researchers have devoted increasing attention to gender differences in psychopathological states and linked COVID-19 strongly to depression,with depression detection becoming a new trend.Developments in research on psychopathology and social media use are unbalanced and uncoordinated across countries/regions,and more indepth clinical studies should be conducted in the future.CONCLUSION After COVID-19,there was an increased level of concern about mental health issues and a changing emphasis on social media use and the impact of public health emergencies.展开更多
Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic plasticity.AD has progressively been recognized as syna ptopathy ...Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic plasticity.AD has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.展开更多
Digital pathology(DP)and its subsidiaries including artificial intelligence(AI)are rapidly making inroads into the area of diagnostic anatomic pathology(AP)including gastrointestinal(GI)pathology.It is poised to revol...Digital pathology(DP)and its subsidiaries including artificial intelligence(AI)are rapidly making inroads into the area of diagnostic anatomic pathology(AP)including gastrointestinal(GI)pathology.It is poised to revolutionize the field of diagnostic AP.Historically,AP has been slow to adopt digital technology,but this is changing rapidly,with many centers worldwide transitioning to DP.Coupled with advanced techniques of AI such as deep learning and machine learning,DP is likely to transform histopathology from a subjective field to an objective,efficient,and transparent discipline.AI is increasingly integrated into GI pathology,offering numerous advancements and improvements in overall diagnostic accuracy,efficiency,and patient care.Specifically,AI in GI pathology enhances diagnostic accuracy,streamlines workflows,provides predictive insights,integrates multimodal data,supports research,and aids in education and training,ultimately improving patient care and outcomes.This review summarized the latest developments in the role and scope of AI in AP with a focus on GI pathology.The main aim was to provide updates and create awareness among the pathology community.展开更多
Alzheimer's disease(AD) is a progressive and degenerative neurological disease characterized by the deterioration of cognitive functions. While a definitive cure and optimal medication to impede disease progressio...Alzheimer's disease(AD) is a progressive and degenerative neurological disease characterized by the deterioration of cognitive functions. While a definitive cure and optimal medication to impede disease progression are currently unavailable, a plethora of studies have highlighted the potential advantages of exercise rehabilitation for managing this condition. Those studies show that exercise rehabilitation can enhance cognitive function and improve the quality of life for individuals affected by AD. Therefore, exercise rehabilitation has been regarded as one of the most important strategies for managing patients with AD. Herein, we provide a comprehensive analysis of the currently available findings on exercise rehabilitation in patients with AD, with a focus on the exercise types which have shown efficacy when implemented alone or combined with other treatment methods, as well as the potential mechanisms underlying these positive effects. Specifically, we explain how exercise may improve the brain microenvironment and neuronal plasticity. In conclusion, exercise is a cost-effective intervention to enhance cognitive performance and improve quality of life in patients with mild to moderate cognitive dysfunction. Therefore, it can potentially become both a physical activity and a tailored intervention. This review may aid the development of more effective and individualized treatment strategies to address the challenges imposed by this debilitating disease, especially in low-and middle-income countries.展开更多
Transient receptor potential(TRP)channels are strongly associated with colon cancer development and progression.This study leveraged a multivariate Cox regression model on publicly available datasets to construct a TR...Transient receptor potential(TRP)channels are strongly associated with colon cancer development and progression.This study leveraged a multivariate Cox regression model on publicly available datasets to construct a TRP channels-associated gene signature,with further validation of signature in real world samples from our hospital treated patient samples.Kaplan-Meier(K-M)survival analysis and receiver operating characteristic(ROC)curves were employed to evaluate this gene signature’s predictive accuracy and robustness in both training and testing cohorts,respectively.Additionally,the study utilized the CIBERSORT algorithm and single-sample gene set enrichment analysis to explore the signature’s immune infiltration landscape and underlying functional implications.The support vector machine algorithm was applied to evaluate the signature’s potential in predicting chemotherapy outcomes.The findings unveiled a novel three TRP channels-related gene signature(MCOLN1,TRPM5,and TRPV4)in colon adenocarcinoma(COAD).The ROC and K-M survival curves in the training dataset(AUC=0.761;p=1.58e-05)and testing dataset(AUC=0.699;p=0.004)showed the signature’s robust predictive capability for the overall survival of COAD patients.Analysis of the immune infiltration landscape associated with the signature revealed higher immune infiltration,especially an increased presence of M2 macrophages,in high-risk group patients compared to their low-risk counterparts.High-risk score patients also exhibited potential responsiveness to immune checkpoint inhibitor therapy,evident through increased CD86 and PD-1 expression profiles.Moreover,the TRPM5 gene within the signature was highly expressed in the chemoresistance group(p=0.00095)and associated with poor prognosis(p=0.036)in COAD patients,highlighting its role as a hub gene of chemoresistance.Ultimately,this signature emerged as an independent prognosis factor for COAD patients(p=6.48e-06)and expression of model gene are validated by public data and real-world patients.Overall,this bioinformatics study provides valuable insights into the prognostic implications and potential chemotherapy resistance mechanisms associated with TRPs-related genes in colon cancer.展开更多
BACKGROUND While primary intestinal lymphangiectasia(PIL)is considered a rare condition,there have been several reported cases in adults.Nevertheless,the absence of clear guidance from diagnosis to treatment and progn...BACKGROUND While primary intestinal lymphangiectasia(PIL)is considered a rare condition,there have been several reported cases in adults.Nevertheless,the absence of clear guidance from diagnosis to treatment and prognosis poses challenges for both physicians and patients.AIM To enhance understanding by investigating clinical presentation,diagnosis,treatment,complications,and prognoses in adult PIL cases.METHODS We enrolled adult patients diagnosed with PIL between March 2016 and September 2021.The primary outcome involved examining the diagnosis and treatment process of these patients.The secondary outcomes included identifying complications(infections,thromboembolism)and assessing prognoses(frequency of hospitalization and mortality)during the follow-up period.RESULTS Among the 12 included patients,peripheral edema(100%)and diarrhea(75%)were the main presenting complaints.Laboratory tests showed that all the pati-ents exhibited symptoms of hypoalbuminemia and hypogammaglobulinemia.Radiologically,the predominant findings were edema of the small intestine(67%)and ascites(58%).The typical endoscopic finding with a snowflake appearance was observed in 75%of patients.Among the 12 patients,two responded positive-ly to octreotide and sirolimus,and eight who could undergo maintenance therapy discontinued subsequently.Complications due to PIL led to infection in half of the patients,thromboembolism in three patients,and one death.CONCLUSION PIL can be diagnosed in adults across various age groups,with different severity and treatment responses among patients,leading to diverse complications and prognoses.Consequently,tailored treatments will be necessary.We anticipate that our findings will contribute to the management of PIL,an etiology of protein-losing enteropathy.展开更多
BACKGROUND Information on liver involvement in patients with coronavirus disease 2019 is currently fragmented.AIM To highlight the pathological changes found during the autopsy of severe acute respiratory syndrome cor...BACKGROUND Information on liver involvement in patients with coronavirus disease 2019 is currently fragmented.AIM To highlight the pathological changes found during the autopsy of severe acute respiratory syndrome coronavirus 2 positive patients.METHODS A systematic literature search on PubMed was carried out until June 21,2022.RESULTS A literature review reveals that pre-existing liver disease and elevation of liver enzyme in these patients are not common;liver enzyme elevations tend to be seen in those in critical conditions.Despite the poor expression of viral receptors in the liver,it seems that the virus is able to infect this organ and therefore cause liver damage.Unfortunately,to date,the search for the virus inside the liver is not frequent(16%of the cases)and only a small number show the presence of the virus.In most of the autopsy cases,macroscopic assessment is lacking,while microscopic evaluation of livers has revealed the frequent presence of congestion(42.7%)and steatosis(41.6%).Less frequent is the finding of hepatic inflammation or necrosis(19%)and portal inflammation(18%).The presence of microthrombi,frequently found in the lungs,is infrequent in the liver,with only 12%of cases presenting thrombotic formations within the vascular tree.CONCLUSION To date,the greatest problem in interpreting these modifications remains the association of the damage with the direct action of the virus,rather than with the inflammation or alterations induced by hypoxia and hypovolemia in patients undergoing oxygen therapy and decompensated patients.展开更多
The gut microbiome interacts with the host to maintain body homeostasis,with gut microbial dysbiosis implicated in many diseases.However,the underlying mechanisms of gut microbe regulation of host behavior and brain f...The gut microbiome interacts with the host to maintain body homeostasis,with gut microbial dysbiosis implicated in many diseases.However,the underlying mechanisms of gut microbe regulation of host behavior and brain functions remain unclear.This study aimed to elucidate the influence of gut microbiota on brain functions via post-translational modification mechanisms in the presence or absence of bacteria without any stimulation.We conducted succinylome analysis of hippocampal proteins in germ-free(GF)and specific pathogen-free(SPF)mice and metagenomic analysis of feces from SPF mice.These results were integrated with previously reported hippocampal acetylome and phosphorylome data from the same batch of mice.Subsequent bioinformatics analyses revealed 584 succinylation sites on 455 proteins,including 54 up-regulated succinylation sites on 91 proteins and 99 down-regulated sites on 51 proteins in the GF mice compared to the SPF mice.We constructed a panoramic map of gut microbiota-regulated succinylation,acetylation,and phosphorylation,and identified cross-talk and relative independence between the different types of post-translational modifications in modulating complicated intracellular pathways.Pearson correlation analysis indicated that 13 taxa,predominantly belonging to the Bacteroidetes phylum,were correlated with the biological functions of post-translational modifications.Positive correlations between these taxa and succinylation and negative correlations between these taxa and acetylation were identified in the modulation of intracellular pathways.This study highlights the hippocampal physiological changes induced by the absence of gut microbiota,and proteomic quantification of succinylation,phosphorylation,and acetylation,contributing to our understanding of the role of the gut microbiome in brain function and behavioral phenotypes.展开更多
BACKGROUND Mycobacterium tuberculosis(TB)is the causative agent of TB,a chronic granulo-matous illness.This disease is prevalent in low-income countries,posing a significant global health challenge.Gastrointestinal TB...BACKGROUND Mycobacterium tuberculosis(TB)is the causative agent of TB,a chronic granulo-matous illness.This disease is prevalent in low-income countries,posing a significant global health challenge.Gastrointestinal TB is one of the three forms.The disease can mimic other intra-abdominal conditions,leading to delayed diagnosis owing to the absence of specific symptoms.While gastric outlet obs-truction(GOO)remains a frequent complication,its incidence has declined with the advent of proton pump inhibitors and Helicobacter pylori eradication therapy.Gastroduodenal TB can cause upper gastrointestinal hemorrhage,obstruction,and malignancy-like tumors.CASE SUMMARY A 23-year-old male presented with recurrent epigastric pain,distension,nausea,vomiting,and weight loss,prompting a referral to a gastroenterologist clinic.Endoscopic examination revealed distorted gastric mucosa and signs of chronic inflammation.However,treatment was interrupted,possibly owing to vomiting or comorbidities such as human immunodeficiency virus infection or diabetes.Subsequent surgical intervention revealed a dilated stomach and diffuse thickening of the duodenal wall.Resection revealed gastric wall effacement with TB.CONCLUSION Primary gastric TB is rare,frequently leading to GOO.Given its rarity,suspicions should be promptly raised when encountering relevant symptoms,often requiring surgical intervention for diagnosis and treatment.展开更多
With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn pu...With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn public attention only in the recent decade.This article summarizes recent works dedicated to understanding the impact of MPs/NPs on the liver-the largest digestive organ,which is one of the primary routes that MPs/NPs enter human bodies.The interrelated mechanisms including oxidative stress,hepatocyte energy re-distribution,cell death and autophagy,as well as immune responses and inflammation,were also featured.In addition,the disturbance of microbiome and gut-liver axis,and the association with clinical diseases such as metabolic dysfunction-associated fatty liver disease,steatohepatitis,liver fibrosis,and cirrhosis were briefly discussed.Finally,we discussed potential directions in regard to this trending topic,highlighted current challenges in research,and proposed possible solutions.展开更多
The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer research.At the time,a variety of activating oncogenic alteration...The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer research.At the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and beyond.Although CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National Cancer Center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of cancer.Looking back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be developed.The quantity and quality of these samples will be compatible with omics analyses.All biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.展开更多
Macrophage migration inhibitory factor(MIF),a multifunctional cytokine,is secreted by various cells and participates in inflammatory reactions,including innate and adaptive immunity.There are some evidences that MIF i...Macrophage migration inhibitory factor(MIF),a multifunctional cytokine,is secreted by various cells and participates in inflammatory reactions,including innate and adaptive immunity.There are some evidences that MIF is involved in many vitreoretinal diseases.For example,MIF can exacerbate many types of uveitis;measurements of MIF levels can be used to monitor the effectiveness of uveitis treatment.MIF also alleviates trauma-induced and glaucoma-induced optic nerve damage.Furthermore,MIF is critical for retinal/choroidal neovascularization,especially complex neovascularization.MIF exacerbates retinal degeneration;thus,anti-MIF therapy may help to mitigate retinal degeneration.MIF protects uveal melanoma from attacks by natural killer cells.The mechanism underlying the effects of MIF in these diseases has been demonstrated:it binds to cluster of differentiation 74,inhibits the c-Jun N-terminal kinase pathway,and triggers mitogen-activated protein kinases,extracellular signal-regulated kinase-1/2,and the phosphoinositide-3-kinase/Akt pathway.MIF also upregulates Toll-like receptor 4 and activates the nuclear factor kappa-B signaling pathway.This review focuses on the structure and function of MIF and its receptors,including the effects of MIF on uveal inflammation,retinal degeneration,optic neuropathy,retinal/choroidal neovascularization,and uveal melanoma.展开更多
BACKGROUND Colorectal cancer(CRC)is a prevalent global malignancy with complex prognostic factors.Tumor-associated macrophages(TAMs)have shown paradoxical associations with CRC survival,particularly concerning the M2 ...BACKGROUND Colorectal cancer(CRC)is a prevalent global malignancy with complex prognostic factors.Tumor-associated macrophages(TAMs)have shown paradoxical associations with CRC survival,particularly concerning the M2 subset.AIM We aimed to establish a simplified protocol for quantifying M2-like TAMs and explore their correlation with clinicopathological factors.METHODS A cross-sectional study included histopathological assessment of paraffinembedded tissue blocks obtained from 43 CRC patients.Using CD68 and CD163 immunohistochemistry,we quantified TAMs in tumor stroma and front,focusing on M2 proportion.Demographic,histopathological,and clinical parameters were collected.RESULTS TAM density was significantly higher at the tumor front,with the M2 proportion three times greater in both zones.The tumor front had a higher M2 proportion,which correlated significantly with advanced tumor stage(P=0.04),pathological nodal involvement(P=0.04),and lymphovascular invasion(LVI,P=0.01).However,no significant association was found between the M2 proportion in the tumor stroma and clinicopathological factors.CONCLUSION Our study introduces a simplified protocol for quantifying M2-like TAMs in CRC tissue samples.We demonstrated a significant correlation between an increased M2 proportion at the tumor front and advanced tumor stage,nodal involvement,and LVI.This suggests that M2-like TAMs might serve as potential indicators of disease progression in CRC,warranting further investigation and potential clinical application.展开更多
The inflammasome is a multiprotein complex involved in innate immunity that mediates the inflammatory response leading to pyroptosis,which is a lytic,inflammatory form of cell death.There is accumulating evidence that...The inflammasome is a multiprotein complex involved in innate immunity that mediates the inflammatory response leading to pyroptosis,which is a lytic,inflammatory form of cell death.There is accumulating evidence that nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3(NLRP3)inflammasome-mediated microglial pyroptosis and NLRP1 inflammasome-mediated neuronal pyroptosis in the brain are closely associated with the pathogenesis of Alzheimer’s disease.In this review,we summarize the possible pathogenic mechanisms of Alzheimer’s disease,focusing on neuroinflammation.We also describe the structures of NLRP3 and NLRP1 and the role their activation plays in Alzheimer’s disease.Finally,we examine the neuroprotective activity of small-molecule inhibitors,endogenous inhibitor proteins,microRNAs,and natural bioactive molecules that target NLRP3 and NLRP1,based on the rationale that inhibiting NLRP3 and NLRP1 inflammasome-mediated pyroptosis can be an effective therapeutic strategy for Alzheimer’s disease.展开更多
BACKGROUND Tumor budding(TB)has emerged as a promising independent prognostic biomarker in colorectal cancer(CRC).The prognostic role of TB has been extensively studied and currently affects clinical decision making i...BACKGROUND Tumor budding(TB)has emerged as a promising independent prognostic biomarker in colorectal cancer(CRC).The prognostic role of TB has been extensively studied and currently affects clinical decision making in patients with stage I and II CRC.However,existing prognostic studies on TB in stage III CRC have been confined to small retrospective cohort studies.Consequently,this study investigated the correlation among TB categories,clinicopathological features,and prognosis in stage III-IV CRC to further enhance the precision and individualization of treatment through refined prognostic risk stratification.AIM To analyze the relationship between TB categories and clinicopathological characteristics and assess their prognostic value in stage III-IV CRC to further refine the prognostic risk stratification of stage III-IV CRC.METHODS The clinical data of 547 CRC patients were collected for this retrospective study.Infiltration at the front edge of the tumor buds was counted according to the 2016 International Tumor Budding Consensus Conference guidelines.RESULTS Multivariate Cox proportional hazards regression analysis demonstrated that chemotherapy(P=0.004),clinical stage IV(P<0.001),≥4 regional lymph node metastases(P=0.004),left-sided colonic cancer(P=0.040),and Bd 2-3(P=0.002)were independent prognostic factors in patients with stage III-IV CRC.Moreover,the density of tumor infiltrating lymphocytes was higher in Bd 1 than in Bd 2-3,both in the tumor stroma and its invasive margin.CONCLUSION TB has an independent predictive prognostic value in patients with stage III-IV CRC.It is recommended to complete the TB report of stage III-IV CRC cases in the standardized pathological report to further refine risk stratification.展开更多
BACKGROUND Pancreatic,periampullary/ampullary,and choledochal adenocarcinomas are aggressive malignancies with a poor prognosis.Immune checkpoint blockade is a promising treatment option for several tumor types.H long...BACKGROUND Pancreatic,periampullary/ampullary,and choledochal adenocarcinomas are aggressive malignancies with a poor prognosis.Immune checkpoint blockade is a promising treatment option for several tumor types.H long terminal repeatassociating 2(HHLA2),which is analogous to programmed death-ligand 1(PDL1),is a recently discovered member of the B7/cluster of differentiation 28 family and is expressed in many malignancies.AIM To analyze the expression of HHLA2 and its association with the pathologic biomarkers that predict sensitivity to immunotherapy.METHODS Ninety-two adenocarcinoma cases located in the pancreas,ampulla,and distal common bile duct were identified.This study assessed 106 pancreaticoduodenectomy and distal/total pancreatectomy samples that were delivered to Ankara City Hospital between 2019 and 2021.Immunohistochemistry was conducted to examine the expression of DNA mismatch repair(MMR),PD-L1,and HHLA2 proteins.RESULTS Patients with high HHLA2 expression had a higher mean age than those with low expression.Low HHLA2 expression was associated with high perineural invasion.HHLA2 expression was low in pathological stage T3(pT)3 cases and high in pathological stage T1,T2,and T4 cases.There was no correlation between HHLA2 expression and the expression of MMR proteins and PD-L1.CONCLUSION Evaluation of HHLA2 expression in microsatellite stable and PD-L1-negative tumors may be useful for predicting the response of individuals to immunotherapy and may serve as a novel therapeutic target for immunotherapy in advanced-stage disease.展开更多
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 an...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.展开更多
Islet beta cells(β-cells)produce insulin in response to high blood glucose levels,which is essential for preserving glucose homeostasis.Voltage-gated ion channels inβ-cells,including Na+,K+,and Ca2+channels,aid in t...Islet beta cells(β-cells)produce insulin in response to high blood glucose levels,which is essential for preserving glucose homeostasis.Voltage-gated ion channels inβ-cells,including Na+,K+,and Ca2+channels,aid in the release of insulin.The epithelial sodium channel alpha subunit(α-ENaC),a voltage-independent sodium ion channel,is also expressed in human pancreatic endocrine cells.However,there is no reported study on the function of ENaC in theβ-cells.In the current study,we found thatα-ENaC was expressed in human pancreatic glandule and pancreatic isletβ-cells.In the pancreas of db/db mice and high-fat diet-induced mice,and in mouse isletβ-cells(MIN6 cells)treated with palmitate,α-ENaC expression was increased.Whenα-ENaC was overexpressed in MIN6 cells,insulin content and glucose-induced insulin secretion were significantly reduced.On the other hand,palmitate injured isletβ-cells and suppressed insulin synthesis and secretion,but increasedα-ENaC expression in MIN6 cells.However,α-ENaC knockout(Scnn1a−/−)in MIN6 cells attenuatedβ-cell disorder induced by palmitate.Furthermore,α-ENaC regulated the ubiquitylation and degradation of sirtuin 2 inβ-cells.α-ENaC also modulatedβ-cell function in correlation with the inositol-requiring enzyme 1 alpha/X-box binding protein 1(IRE1α/XBP1)and protein kinase RNA-like endoplasmic reticulum kinase/C/EBP homologous protein(PERK/CHOP)endoplasmic reticulum stress pathways.These results suggest thatα-ENaC may play a novel role in insulin synthesis and secretion in theβ-cells,and the upregulation ofα-ENaC promotes isletβ-cell dysfunction.In conclusion,α-ENaC may be a key regulator involved in isletβ-cell damage and a potential therapeutic target for type 2 diabetes mellitus.展开更多
To the Editor:Biliary stricture formation at the bilioenteric anastomosis is an infrequent complication(2%-3%)after pancreaticoduodenectomy;the average presentation is within 13-14 months(range from 1 month to 9 years...To the Editor:Biliary stricture formation at the bilioenteric anastomosis is an infrequent complication(2%-3%)after pancreaticoduodenectomy;the average presentation is within 13-14 months(range from 1 month to 9 years)after surgery[1,2].While the etiology is unknown,development of biliary stricture has shown to be more likely if a bile leak occurs in the postoperative period[3,4]and with younger patients[5].展开更多
BACKGROUND Cellular myofibroma is a rare subtype of myofibroma that was first described in 2017.Its diagnosis is often challenging because of its relative rarity,lack of known genetic abnormalities,and expression of m...BACKGROUND Cellular myofibroma is a rare subtype of myofibroma that was first described in 2017.Its diagnosis is often challenging because of its relative rarity,lack of known genetic abnormalities,and expression of muscle markers that can be confused with sarcomas that have myogenic differentiation.Currently,scholars have limited knowledge of this disease,and published cases are few.Further accumulation of diagnostic and treatment experiences is required.CASE SUMMARY A 16-year-old girl experienced left upper limb swelling for 3 years.She sought medical attention at a local hospital 10 months ago,where magnetic resonance imaging revealed a 5-cm soft tissue mass.Needle biopsy performed at a local hospital resulted in the diagnosis of a spindle cell soft tissue sarcoma.The patient was referred to our hospital for limb salvage surgery with endoprosthetic replacement.She was initially diagnosed with a synovial sarcoma.Consequently,clinical management with chemotherapy was continued for the malignant sarcoma.Our pathology department also performed fluorescence in situ hybridization for result validation,which returned negative for SS18 gene breaks,indicating that it was not a synovial sarcoma.Next-generation sequencing was used to identify the SRF-RELA rearrangement.The final pathological diagnosis was a cellular/myofibroblastic neoplasm with an SRF-RELA gene fusion.The patient had initially received two courses of chemotherapy;however,chemotherapy was discontinued after the final diagnosis.CONCLUSION This case was misdiagnosed because of its rare occurrence,benign biological behavior,and pathological similarity to soft tissue sarcoma.展开更多
基金Supported by Guangxi Higher Education Undergraduate Teaching Reform Project,No.2022JGA146Guangxi Educational Science Planning Key Project,No.2022ZJY2791+1 种基金Guangxi Medical University Key Textbook Construction Project,No.Gxmuzdjc2223Guangxi Medical High-Level Key Talents Training“139”Program.
文摘BACKGROUND Despite advances in research on psychopathology and social media use,no comprehensive review has examined published papers on this type of research and considered how it was affected by the coronavirus disease 2019(COVID-19)outbreak.AIM To explore the status of research on psychopathology and social media use before and after the COVID-19 outbreak.METHODS We used Bibliometrix(an R software package)to conduct a scientometric analysis of 4588 relevant studies drawn from the Web of Science Core Collection,PubMed,and Scopus databases.RESULTS Such research output was scarce before COVID-19,but exploded after the pandemic with the publication of a number of high-impact articles.Key authors and institutions,located primarily in developed countries,maintained their core positions,largely uninfluenced by COVID-19;however,research production and collaboration in developing countries increased significantly after COVID-19.Through the analysis of keywords,we identified commonly used methods in this field,together with specific populations,psychopathological conditions,and clinical treatments.Researchers have devoted increasing attention to gender differences in psychopathological states and linked COVID-19 strongly to depression,with depression detection becoming a new trend.Developments in research on psychopathology and social media use are unbalanced and uncoordinated across countries/regions,and more indepth clinical studies should be conducted in the future.CONCLUSION After COVID-19,there was an increased level of concern about mental health issues and a changing emphasis on social media use and the impact of public health emergencies.
文摘Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic plasticity.AD has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.
文摘Digital pathology(DP)and its subsidiaries including artificial intelligence(AI)are rapidly making inroads into the area of diagnostic anatomic pathology(AP)including gastrointestinal(GI)pathology.It is poised to revolutionize the field of diagnostic AP.Historically,AP has been slow to adopt digital technology,but this is changing rapidly,with many centers worldwide transitioning to DP.Coupled with advanced techniques of AI such as deep learning and machine learning,DP is likely to transform histopathology from a subjective field to an objective,efficient,and transparent discipline.AI is increasingly integrated into GI pathology,offering numerous advancements and improvements in overall diagnostic accuracy,efficiency,and patient care.Specifically,AI in GI pathology enhances diagnostic accuracy,streamlines workflows,provides predictive insights,integrates multimodal data,supports research,and aids in education and training,ultimately improving patient care and outcomes.This review summarized the latest developments in the role and scope of AI in AP with a focus on GI pathology.The main aim was to provide updates and create awareness among the pathology community.
基金supported by the National Natural Science Foundation of China,Nos.81971309 (to CY),32170980 (to CY),82260272 (to DL)the Natural Science Foundation of Jiangxi Province,No.20192BAB205078 (to DL)+1 种基金Guangdong Basic and Applied Basic Research Foundation,No.2022B1515020012 (to CY)Shenzhen Fundamental Research Program,Nos.JCYJ20210324123212035 (to CY),RCYX202007141 14644167 (to CY),ZDSYS20220606100801003 (to CY)。
文摘Alzheimer's disease(AD) is a progressive and degenerative neurological disease characterized by the deterioration of cognitive functions. While a definitive cure and optimal medication to impede disease progression are currently unavailable, a plethora of studies have highlighted the potential advantages of exercise rehabilitation for managing this condition. Those studies show that exercise rehabilitation can enhance cognitive function and improve the quality of life for individuals affected by AD. Therefore, exercise rehabilitation has been regarded as one of the most important strategies for managing patients with AD. Herein, we provide a comprehensive analysis of the currently available findings on exercise rehabilitation in patients with AD, with a focus on the exercise types which have shown efficacy when implemented alone or combined with other treatment methods, as well as the potential mechanisms underlying these positive effects. Specifically, we explain how exercise may improve the brain microenvironment and neuronal plasticity. In conclusion, exercise is a cost-effective intervention to enhance cognitive performance and improve quality of life in patients with mild to moderate cognitive dysfunction. Therefore, it can potentially become both a physical activity and a tailored intervention. This review may aid the development of more effective and individualized treatment strategies to address the challenges imposed by this debilitating disease, especially in low-and middle-income countries.
基金the Ethics Committee of University Magdeburg(Ethical code:33/0119.03.2001).
文摘Transient receptor potential(TRP)channels are strongly associated with colon cancer development and progression.This study leveraged a multivariate Cox regression model on publicly available datasets to construct a TRP channels-associated gene signature,with further validation of signature in real world samples from our hospital treated patient samples.Kaplan-Meier(K-M)survival analysis and receiver operating characteristic(ROC)curves were employed to evaluate this gene signature’s predictive accuracy and robustness in both training and testing cohorts,respectively.Additionally,the study utilized the CIBERSORT algorithm and single-sample gene set enrichment analysis to explore the signature’s immune infiltration landscape and underlying functional implications.The support vector machine algorithm was applied to evaluate the signature’s potential in predicting chemotherapy outcomes.The findings unveiled a novel three TRP channels-related gene signature(MCOLN1,TRPM5,and TRPV4)in colon adenocarcinoma(COAD).The ROC and K-M survival curves in the training dataset(AUC=0.761;p=1.58e-05)and testing dataset(AUC=0.699;p=0.004)showed the signature’s robust predictive capability for the overall survival of COAD patients.Analysis of the immune infiltration landscape associated with the signature revealed higher immune infiltration,especially an increased presence of M2 macrophages,in high-risk group patients compared to their low-risk counterparts.High-risk score patients also exhibited potential responsiveness to immune checkpoint inhibitor therapy,evident through increased CD86 and PD-1 expression profiles.Moreover,the TRPM5 gene within the signature was highly expressed in the chemoresistance group(p=0.00095)and associated with poor prognosis(p=0.036)in COAD patients,highlighting its role as a hub gene of chemoresistance.Ultimately,this signature emerged as an independent prognosis factor for COAD patients(p=6.48e-06)and expression of model gene are validated by public data and real-world patients.Overall,this bioinformatics study provides valuable insights into the prognostic implications and potential chemotherapy resistance mechanisms associated with TRPs-related genes in colon cancer.
文摘BACKGROUND While primary intestinal lymphangiectasia(PIL)is considered a rare condition,there have been several reported cases in adults.Nevertheless,the absence of clear guidance from diagnosis to treatment and prognosis poses challenges for both physicians and patients.AIM To enhance understanding by investigating clinical presentation,diagnosis,treatment,complications,and prognoses in adult PIL cases.METHODS We enrolled adult patients diagnosed with PIL between March 2016 and September 2021.The primary outcome involved examining the diagnosis and treatment process of these patients.The secondary outcomes included identifying complications(infections,thromboembolism)and assessing prognoses(frequency of hospitalization and mortality)during the follow-up period.RESULTS Among the 12 included patients,peripheral edema(100%)and diarrhea(75%)were the main presenting complaints.Laboratory tests showed that all the pati-ents exhibited symptoms of hypoalbuminemia and hypogammaglobulinemia.Radiologically,the predominant findings were edema of the small intestine(67%)and ascites(58%).The typical endoscopic finding with a snowflake appearance was observed in 75%of patients.Among the 12 patients,two responded positive-ly to octreotide and sirolimus,and eight who could undergo maintenance therapy discontinued subsequently.Complications due to PIL led to infection in half of the patients,thromboembolism in three patients,and one death.CONCLUSION PIL can be diagnosed in adults across various age groups,with different severity and treatment responses among patients,leading to diverse complications and prognoses.Consequently,tailored treatments will be necessary.We anticipate that our findings will contribute to the management of PIL,an etiology of protein-losing enteropathy.
文摘BACKGROUND Information on liver involvement in patients with coronavirus disease 2019 is currently fragmented.AIM To highlight the pathological changes found during the autopsy of severe acute respiratory syndrome coronavirus 2 positive patients.METHODS A systematic literature search on PubMed was carried out until June 21,2022.RESULTS A literature review reveals that pre-existing liver disease and elevation of liver enzyme in these patients are not common;liver enzyme elevations tend to be seen in those in critical conditions.Despite the poor expression of viral receptors in the liver,it seems that the virus is able to infect this organ and therefore cause liver damage.Unfortunately,to date,the search for the virus inside the liver is not frequent(16%of the cases)and only a small number show the presence of the virus.In most of the autopsy cases,macroscopic assessment is lacking,while microscopic evaluation of livers has revealed the frequent presence of congestion(42.7%)and steatosis(41.6%).Less frequent is the finding of hepatic inflammation or necrosis(19%)and portal inflammation(18%).The presence of microthrombi,frequently found in the lungs,is infrequent in the liver,with only 12%of cases presenting thrombotic formations within the vascular tree.CONCLUSION To date,the greatest problem in interpreting these modifications remains the association of the damage with the direct action of the virus,rather than with the inflammation or alterations induced by hypoxia and hypovolemia in patients undergoing oxygen therapy and decompensated patients.
基金supported by the Natural Science Foundation Project of China(81820108015,82201683)China Postdoctoral Science Foundation(2021M693926,2020TQ0393,2020M683634XB)+1 种基金Chongqing Science&Technology Commission(cstc2021jcyj-bshX0150,cstc2021jcyj-bshX0201)Special Funding for Chongqing Postdoctoral Research Projects(2021XMT001)。
文摘The gut microbiome interacts with the host to maintain body homeostasis,with gut microbial dysbiosis implicated in many diseases.However,the underlying mechanisms of gut microbe regulation of host behavior and brain functions remain unclear.This study aimed to elucidate the influence of gut microbiota on brain functions via post-translational modification mechanisms in the presence or absence of bacteria without any stimulation.We conducted succinylome analysis of hippocampal proteins in germ-free(GF)and specific pathogen-free(SPF)mice and metagenomic analysis of feces from SPF mice.These results were integrated with previously reported hippocampal acetylome and phosphorylome data from the same batch of mice.Subsequent bioinformatics analyses revealed 584 succinylation sites on 455 proteins,including 54 up-regulated succinylation sites on 91 proteins and 99 down-regulated sites on 51 proteins in the GF mice compared to the SPF mice.We constructed a panoramic map of gut microbiota-regulated succinylation,acetylation,and phosphorylation,and identified cross-talk and relative independence between the different types of post-translational modifications in modulating complicated intracellular pathways.Pearson correlation analysis indicated that 13 taxa,predominantly belonging to the Bacteroidetes phylum,were correlated with the biological functions of post-translational modifications.Positive correlations between these taxa and succinylation and negative correlations between these taxa and acetylation were identified in the modulation of intracellular pathways.This study highlights the hippocampal physiological changes induced by the absence of gut microbiota,and proteomic quantification of succinylation,phosphorylation,and acetylation,contributing to our understanding of the role of the gut microbiome in brain function and behavioral phenotypes.
文摘BACKGROUND Mycobacterium tuberculosis(TB)is the causative agent of TB,a chronic granulo-matous illness.This disease is prevalent in low-income countries,posing a significant global health challenge.Gastrointestinal TB is one of the three forms.The disease can mimic other intra-abdominal conditions,leading to delayed diagnosis owing to the absence of specific symptoms.While gastric outlet obs-truction(GOO)remains a frequent complication,its incidence has declined with the advent of proton pump inhibitors and Helicobacter pylori eradication therapy.Gastroduodenal TB can cause upper gastrointestinal hemorrhage,obstruction,and malignancy-like tumors.CASE SUMMARY A 23-year-old male presented with recurrent epigastric pain,distension,nausea,vomiting,and weight loss,prompting a referral to a gastroenterologist clinic.Endoscopic examination revealed distorted gastric mucosa and signs of chronic inflammation.However,treatment was interrupted,possibly owing to vomiting or comorbidities such as human immunodeficiency virus infection or diabetes.Subsequent surgical intervention revealed a dilated stomach and diffuse thickening of the duodenal wall.Resection revealed gastric wall effacement with TB.CONCLUSION Primary gastric TB is rare,frequently leading to GOO.Given its rarity,suspicions should be promptly raised when encountering relevant symptoms,often requiring surgical intervention for diagnosis and treatment.
文摘With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn public attention only in the recent decade.This article summarizes recent works dedicated to understanding the impact of MPs/NPs on the liver-the largest digestive organ,which is one of the primary routes that MPs/NPs enter human bodies.The interrelated mechanisms including oxidative stress,hepatocyte energy re-distribution,cell death and autophagy,as well as immune responses and inflammation,were also featured.In addition,the disturbance of microbiome and gut-liver axis,and the association with clinical diseases such as metabolic dysfunction-associated fatty liver disease,steatohepatitis,liver fibrosis,and cirrhosis were briefly discussed.Finally,we discussed potential directions in regard to this trending topic,highlighted current challenges in research,and proposed possible solutions.
文摘The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer research.At the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and beyond.Although CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National Cancer Center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of cancer.Looking back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be developed.The quantity and quality of these samples will be compatible with omics analyses.All biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.
基金supported by the Key Program of Natural Science Foundation of Shaanxi Province,No.2021JZ-60(to HZ)。
文摘Macrophage migration inhibitory factor(MIF),a multifunctional cytokine,is secreted by various cells and participates in inflammatory reactions,including innate and adaptive immunity.There are some evidences that MIF is involved in many vitreoretinal diseases.For example,MIF can exacerbate many types of uveitis;measurements of MIF levels can be used to monitor the effectiveness of uveitis treatment.MIF also alleviates trauma-induced and glaucoma-induced optic nerve damage.Furthermore,MIF is critical for retinal/choroidal neovascularization,especially complex neovascularization.MIF exacerbates retinal degeneration;thus,anti-MIF therapy may help to mitigate retinal degeneration.MIF protects uveal melanoma from attacks by natural killer cells.The mechanism underlying the effects of MIF in these diseases has been demonstrated:it binds to cluster of differentiation 74,inhibits the c-Jun N-terminal kinase pathway,and triggers mitogen-activated protein kinases,extracellular signal-regulated kinase-1/2,and the phosphoinositide-3-kinase/Akt pathway.MIF also upregulates Toll-like receptor 4 and activates the nuclear factor kappa-B signaling pathway.This review focuses on the structure and function of MIF and its receptors,including the effects of MIF on uveal inflammation,retinal degeneration,optic neuropathy,retinal/choroidal neovascularization,and uveal melanoma.
文摘BACKGROUND Colorectal cancer(CRC)is a prevalent global malignancy with complex prognostic factors.Tumor-associated macrophages(TAMs)have shown paradoxical associations with CRC survival,particularly concerning the M2 subset.AIM We aimed to establish a simplified protocol for quantifying M2-like TAMs and explore their correlation with clinicopathological factors.METHODS A cross-sectional study included histopathological assessment of paraffinembedded tissue blocks obtained from 43 CRC patients.Using CD68 and CD163 immunohistochemistry,we quantified TAMs in tumor stroma and front,focusing on M2 proportion.Demographic,histopathological,and clinical parameters were collected.RESULTS TAM density was significantly higher at the tumor front,with the M2 proportion three times greater in both zones.The tumor front had a higher M2 proportion,which correlated significantly with advanced tumor stage(P=0.04),pathological nodal involvement(P=0.04),and lymphovascular invasion(LVI,P=0.01).However,no significant association was found between the M2 proportion in the tumor stroma and clinicopathological factors.CONCLUSION Our study introduces a simplified protocol for quantifying M2-like TAMs in CRC tissue samples.We demonstrated a significant correlation between an increased M2 proportion at the tumor front and advanced tumor stage,nodal involvement,and LVI.This suggests that M2-like TAMs might serve as potential indicators of disease progression in CRC,warranting further investigation and potential clinical application.
基金supported by the Natural Science Foundation of Zhejiang Province of China,Nos.LQ22H090003(to JJ),LTGY23C090001(to XZ),LY23H020008(to BH)Sci-Tech Planning Project of Jiaxing,Nos.2021AY30001(to XZ)and 2022AY30020(to JJ).
文摘The inflammasome is a multiprotein complex involved in innate immunity that mediates the inflammatory response leading to pyroptosis,which is a lytic,inflammatory form of cell death.There is accumulating evidence that nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3(NLRP3)inflammasome-mediated microglial pyroptosis and NLRP1 inflammasome-mediated neuronal pyroptosis in the brain are closely associated with the pathogenesis of Alzheimer’s disease.In this review,we summarize the possible pathogenic mechanisms of Alzheimer’s disease,focusing on neuroinflammation.We also describe the structures of NLRP3 and NLRP1 and the role their activation plays in Alzheimer’s disease.Finally,we examine the neuroprotective activity of small-molecule inhibitors,endogenous inhibitor proteins,microRNAs,and natural bioactive molecules that target NLRP3 and NLRP1,based on the rationale that inhibiting NLRP3 and NLRP1 inflammasome-mediated pyroptosis can be an effective therapeutic strategy for Alzheimer’s disease.
基金National Key R&D Program of China,No.2022YFF1203300.
文摘BACKGROUND Tumor budding(TB)has emerged as a promising independent prognostic biomarker in colorectal cancer(CRC).The prognostic role of TB has been extensively studied and currently affects clinical decision making in patients with stage I and II CRC.However,existing prognostic studies on TB in stage III CRC have been confined to small retrospective cohort studies.Consequently,this study investigated the correlation among TB categories,clinicopathological features,and prognosis in stage III-IV CRC to further enhance the precision and individualization of treatment through refined prognostic risk stratification.AIM To analyze the relationship between TB categories and clinicopathological characteristics and assess their prognostic value in stage III-IV CRC to further refine the prognostic risk stratification of stage III-IV CRC.METHODS The clinical data of 547 CRC patients were collected for this retrospective study.Infiltration at the front edge of the tumor buds was counted according to the 2016 International Tumor Budding Consensus Conference guidelines.RESULTS Multivariate Cox proportional hazards regression analysis demonstrated that chemotherapy(P=0.004),clinical stage IV(P<0.001),≥4 regional lymph node metastases(P=0.004),left-sided colonic cancer(P=0.040),and Bd 2-3(P=0.002)were independent prognostic factors in patients with stage III-IV CRC.Moreover,the density of tumor infiltrating lymphocytes was higher in Bd 1 than in Bd 2-3,both in the tumor stroma and its invasive margin.CONCLUSION TB has an independent predictive prognostic value in patients with stage III-IV CRC.It is recommended to complete the TB report of stage III-IV CRC cases in the standardized pathological report to further refine risk stratification.
文摘BACKGROUND Pancreatic,periampullary/ampullary,and choledochal adenocarcinomas are aggressive malignancies with a poor prognosis.Immune checkpoint blockade is a promising treatment option for several tumor types.H long terminal repeatassociating 2(HHLA2),which is analogous to programmed death-ligand 1(PDL1),is a recently discovered member of the B7/cluster of differentiation 28 family and is expressed in many malignancies.AIM To analyze the expression of HHLA2 and its association with the pathologic biomarkers that predict sensitivity to immunotherapy.METHODS Ninety-two adenocarcinoma cases located in the pancreas,ampulla,and distal common bile duct were identified.This study assessed 106 pancreaticoduodenectomy and distal/total pancreatectomy samples that were delivered to Ankara City Hospital between 2019 and 2021.Immunohistochemistry was conducted to examine the expression of DNA mismatch repair(MMR),PD-L1,and HHLA2 proteins.RESULTS Patients with high HHLA2 expression had a higher mean age than those with low expression.Low HHLA2 expression was associated with high perineural invasion.HHLA2 expression was low in pathological stage T3(pT)3 cases and high in pathological stage T1,T2,and T4 cases.There was no correlation between HHLA2 expression and the expression of MMR proteins and PD-L1.CONCLUSION Evaluation of HHLA2 expression in microsatellite stable and PD-L1-negative tumors may be useful for predicting the response of individuals to immunotherapy and may serve as a novel therapeutic target for immunotherapy in advanced-stage disease.
基金Supported by National High Level Hospital Clinical Research Funding,No.2022-PUMCH-B-022 and No.2022-PUMCH-D-002CAMS Innovation Fund for Medical Sciences,No.2021-1-I2M-003+1 种基金Undergraduate Innovation Program,No.2023-zglc-06034National Key Clinical Specialty Construction Project,No.ZK108000。
文摘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.
基金supported by the National Natural Science Foundation of China(Grant Nos.81870467 and 82270717 to XL,and 81970673 to FC)China Postdoctoral Science Foundation(Grant No.2023M731630 to XZhang)Postgraduate Research and Practice Innovation Program of Jiangsu Province(Grant No.KYCX21_1588 to XZhou).
文摘Islet beta cells(β-cells)produce insulin in response to high blood glucose levels,which is essential for preserving glucose homeostasis.Voltage-gated ion channels inβ-cells,including Na+,K+,and Ca2+channels,aid in the release of insulin.The epithelial sodium channel alpha subunit(α-ENaC),a voltage-independent sodium ion channel,is also expressed in human pancreatic endocrine cells.However,there is no reported study on the function of ENaC in theβ-cells.In the current study,we found thatα-ENaC was expressed in human pancreatic glandule and pancreatic isletβ-cells.In the pancreas of db/db mice and high-fat diet-induced mice,and in mouse isletβ-cells(MIN6 cells)treated with palmitate,α-ENaC expression was increased.Whenα-ENaC was overexpressed in MIN6 cells,insulin content and glucose-induced insulin secretion were significantly reduced.On the other hand,palmitate injured isletβ-cells and suppressed insulin synthesis and secretion,but increasedα-ENaC expression in MIN6 cells.However,α-ENaC knockout(Scnn1a−/−)in MIN6 cells attenuatedβ-cell disorder induced by palmitate.Furthermore,α-ENaC regulated the ubiquitylation and degradation of sirtuin 2 inβ-cells.α-ENaC also modulatedβ-cell function in correlation with the inositol-requiring enzyme 1 alpha/X-box binding protein 1(IRE1α/XBP1)and protein kinase RNA-like endoplasmic reticulum kinase/C/EBP homologous protein(PERK/CHOP)endoplasmic reticulum stress pathways.These results suggest thatα-ENaC may play a novel role in insulin synthesis and secretion in theβ-cells,and the upregulation ofα-ENaC promotes isletβ-cell dysfunction.In conclusion,α-ENaC may be a key regulator involved in isletβ-cell damage and a potential therapeutic target for type 2 diabetes mellitus.
文摘To the Editor:Biliary stricture formation at the bilioenteric anastomosis is an infrequent complication(2%-3%)after pancreaticoduodenectomy;the average presentation is within 13-14 months(range from 1 month to 9 years)after surgery[1,2].While the etiology is unknown,development of biliary stricture has shown to be more likely if a bile leak occurs in the postoperative period[3,4]and with younger patients[5].
文摘BACKGROUND Cellular myofibroma is a rare subtype of myofibroma that was first described in 2017.Its diagnosis is often challenging because of its relative rarity,lack of known genetic abnormalities,and expression of muscle markers that can be confused with sarcomas that have myogenic differentiation.Currently,scholars have limited knowledge of this disease,and published cases are few.Further accumulation of diagnostic and treatment experiences is required.CASE SUMMARY A 16-year-old girl experienced left upper limb swelling for 3 years.She sought medical attention at a local hospital 10 months ago,where magnetic resonance imaging revealed a 5-cm soft tissue mass.Needle biopsy performed at a local hospital resulted in the diagnosis of a spindle cell soft tissue sarcoma.The patient was referred to our hospital for limb salvage surgery with endoprosthetic replacement.She was initially diagnosed with a synovial sarcoma.Consequently,clinical management with chemotherapy was continued for the malignant sarcoma.Our pathology department also performed fluorescence in situ hybridization for result validation,which returned negative for SS18 gene breaks,indicating that it was not a synovial sarcoma.Next-generation sequencing was used to identify the SRF-RELA rearrangement.The final pathological diagnosis was a cellular/myofibroblastic neoplasm with an SRF-RELA gene fusion.The patient had initially received two courses of chemotherapy;however,chemotherapy was discontinued after the final diagnosis.CONCLUSION This case was misdiagnosed because of its rare occurrence,benign biological behavior,and pathological similarity to soft tissue sarcoma.