The Relationship between Mental Disorders and Personality of Outpatients in a Psychiatric Clinic in Nanjing, China

Psychosis has increasingly become a social problem,emphasizing the need to understand the relationship between mental disorders and personality.This study aimed to investigate the relationship between mental disorders and personality among psychiatric outpatients based on real-world data.Symptom Checklist 90(SCL-90)and Eysenck Personality Questionnaire(EPQ)were used to evaluate the personality and psychopathological symptoms of patients(n=8409)in the Psychiatric Outpatient Department at Nanjing Drum Tower Hospital.t-test was used to compare scores between patients and national norms.Pearson’s correlation coefficient and path analysis were used to explore the relationship between mental health status and personality.The correlation coefficient between the neuroticism(N)score and each factor score of the SCL-90 test,as well as the correlation between psychoticism(P)and hostility and paranoia,exceeded 0.4.Path analysis revealed that the standardized path coefficients of N score and SCL-90 were all higher than 0.4.In addition,the standardized path coefficient of hostility and paranoia on P score were 0.313 and 0.280,respectively.Interpersonal sensitivity,depression and obsessive-compulsive symptoms were affected by extraversion(E)score,with standardized path coefficients of-0.149,-0.138,and-0.105,respectively.The path analysis also showed the direct and indirect effects of age,gender,education,and marital status on SCL-90.Patients characterized as melancholic had higher scores in all factors of SCL-90.In conclusion,mental health was related to personality traits of neuroticism,psychoticism and introversion.

Mitochondrial dysfunction and quality control lie at the heart of subarachnoid hemorrhage

The dramatic increase in intracranial pressure after subarachnoid hemorrhage leads to a decrease in cerebral perfusion pressure and a reduction in cerebral blood flow.Mitochondria are directly affected by direct factors such as ischemia,hypoxia,excitotoxicity,and toxicity of free hemoglobin and its degradation products,which trigger mitochondrial dysfunction.Dysfunctional mitochondria release large amounts of reactive oxygen species,inflammatory mediators,and apoptotic proteins that activate apoptotic pathways,further damaging cells.In response to this array of damage,cells have adopted multiple mitochondrial quality control mechanisms through evolution,including mitochondrial protein quality control,mitochondrial dynamics,mitophagy,mitochondrial biogenesis,and intercellular mitochondrial transfer,to maintain mitochondrial homeostasis under pathological conditions.Specific interventions targeting mitochondrial quality control mechanisms have emerged as promising therapeutic strategies for subarachnoid hemorrhage.This review provides an overview of recent research advances in mitochondrial pathophysiological processes after subarachnoid hemorrhage,particularly mitochondrial quality control mechanisms.It also presents potential therapeutic strategies to target mitochondrial quality control in subarachnoid hemorrhage.

How mesenchymal stem cells transform into adipocytes:Overview of the current understanding of adipogenic differentiation

Mesenchymal stem cells(MSCs)are stem/progenitor cells capable of self-renewal and differentiation into osteoblasts,chondrocytes and adipocytes.The transformation of multipotent MSCs to adipocytes mainly involves two subsequent steps from MSCs to preadipocytes and further preadipocytes into adipocytes,in which the process MSCs are precisely controlled to commit to the adipogenic lineage and then mature into adipocytes.Previous studies have shown that the master transcription factors C/enhancer-binding protein alpha and peroxisome proliferation activator receptor gamma play vital roles in adipogenesis.However,the mechanism underlying the adipogenic differentiation of MSCs is not fully understood.Here,the current knowledge of adipogenic differentiation in MSCs is reviewed,focusing on signaling pathways,noncoding RNAs and epigenetic effects on DNA methylation and acetylation during MSC differentiation.Finally,the relationship between maladipogenic differentiation and diseases is briefly discussed.We hope that this review can broaden and deepen our understanding of how MSCs turn into adipocytes.

Mycobacterium smegmatis enhances shikonin-induced immunogenic cell death—an efficient in situ tumor vaccine strategy

Tumor vaccines are a promising avenue in cancer immunotherapy.Despite the progress in targeting specific immune epitopes,tumor cells lacking these epitopes can evade the treatment.Here,we aimed to construct an efficient in situ tumor vaccine called Vac-SM,utilizing shikonin(SKN)to induce immunogenic cell death(ICD)and Mycobacterium smegmatis as an immune adjuvant to enhance in situ tumor vaccine efficacy.SKN showed a dose-dependent and time-dependent cytotoxic effect on the tumor cell line and induced ICD in tumor cells as evidenced by the CCK-8 assay and the detection of the expression of relevant indicators,respectively.Compared with the control group,the in situ Vac-SM injection in mouse subcutaneous metastatic tumors significantly inhibited tumor growth and distant tumor metastasis,while also improving survival rates.Mycobacterium smegmatis effectively induced maturation and activation of bone marrow-derived dendritic cells(DCs),and in vivo tumor-draining lymph nodes showed an increased maturation of DCs and a higher proportion of effector memory T-cell subsets with the Vac-SM treatment,based on flow cytometry analysis results.Collectively,the Vac-SM vaccine effectively induces ICD,improves antigen presentation by DCs,activates a specific systemic antitumor T-cell immune response,exhibits a favorable safety profile,and holds the promise for clinical translation for local tumor immunotherapy.

Transjugular intrahepatic portosystemic shunt:A promising therapy for recompensation in cirrhotic patients

This is a retrospective study focused on recompensation after transjugular intrahepatic portosystemic shunt(TIPS)procedure.The authors confirmed TIPS could be a treatment for recompensation of patients with cirrhosis according to Baveno VII.The paper identified age and post-TIPS portal pressure gradient as independent predictors of recompensation in patients with decompensated cirrhosis after TIPS.These results need to be validated in a larger prospective cohort.

Ruxolitinib improves the inflammatory microenvironment,restores glutamate homeostasis,and promotes functional recovery after spinal cord injury

The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord injury.Ruxolitinib,a JAK-STAT inhibitor,exhibits effectiveness in autoimmune diseases,arthritis,and managing inflammatory cytokine storms.Although studies have shown the neuroprotective potential of ruxolitinib in neurological trauma,the exact mechanism by which it enhances functional recovery after spinal cord injury,particularly its effect on astrocytes,remains unclear.To address this gap,we established a mouse model of T10 spinal cord contusion and found that ruxolitinib effectively improved hindlimb motor function and reduced the area of spinal cord injury.Transcriptome sequencing analysis showed that ruxolitinib alleviated inflammation and immune response after spinal cord injury,restored EAAT2 expression,reduced glutamate levels,and alleviated excitatory toxicity.Furthermore,ruxolitinib inhibited the phosphorylation of JAK2 and STAT3 in the injured spinal cord and decreased the phosphorylation level of nuclear factor kappa-B and the expression of inflammatory factors interleukin-1β,interleukin-6,and tumor necrosis factor-α.Additionally,in glutamate-induced excitotoxicity astrocytes,ruxolitinib restored EAAT2 expression and increased glutamate uptake by inhibiting the activation of STAT3,thereby reducing glutamate-induced neurotoxicity,calcium influx,oxidative stress,and cell apoptosis,and increasing the complexity of dendritic branching.Collectively,these results indicate that ruxolitinib restores glutamate homeostasis by rescuing the expression of EAAT2 in astrocytes,reduces neurotoxicity,and effectively alleviates inflammatory and immune responses after spinal cord injury,thereby promoting functional recovery after spinal cord injury.

A Polyvinyl Alcohol/Acrylamide Hydrogel with Enhanced Mechanical Properties Promotes Full-Thickness Skin Defect Healing by Regulating Immunomodulation and Angiogenesis Through Paracrine Secretion

Hydrogel-based tissue-engineered skin has attracted increased attention due to its potential to restore the structural integrity and functionality of skin.However,the mechanical properties of hydrogel scaffolds and natural skin are substantially different.Here,we developed a polyvinyl alcohol(PVA)/acrylamide based interpenetrating network(IPN)hydrogel that was surface modified with polydopamine(PDA)and termed Dopa-gel.The Dopa-gel exhibited mechanical properties similar to native skin tissue and a superior ability to modulate paracrine functions.Furthermore,a tough scaffold with tensile resistance was fabricated using this hydrogel by three-dimensional printing.The results showed that the interpenetration of PVA,alginate,and polyacrylamide networks notably enhanced the mechanical properties of the hydrogel.Surface modification with PDA endowed the hydrogels with increased secretion of immunomodulatory and proangiogenic factors.In an in vivo model,Dopa-gel treatment accelerated wound closure,increased vascularization,and promoted a shift in macrophages from a proinflammatory M1 phenotype to a prohealing and anti-inflammatory M2 phenotype within the wound area.Mechanistically,the focal adhesion kinase(FAK)/extracellular signal-related kinase(ERK)signaling pathway may mediate the promotion of skin defect healing by increasing paracrine secretion via the Dopa-gel.Additionally,proangiogenic factors can be induced through Rho-associated kinase-2(ROCK-2)/vascular endothelial growth factor(VEGF)-mediated paracrine secretion under tensile stress conditions.Taken together,these findings suggest that the multifunctional Dopa-gel,which has good mechanical properties similar to those of native skin tissue and enhanced immunomodulatory and angiogenic properties,is a promising scaffold for skin tissue regeneration.

Clinical manifestation,lifestyle,and treatment patterns of chronic erosive gastritis:A multicenter real-world study in China

BACKGROUND Although chronic erosive gastritis(CEG)is common,its clinical characteristics have not been fully elucidated.The lack of consensus regarding its treatment has resulted in varied treatment regimens.AIM To explore the clinical characteristics,treatment patterns,and short-term outcomes in CEG patients in China.METHODS We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology.Patients and treating physicians completed a questionnaire regarding history,endoscopic findings,and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment.RESULTS Three thousand five hundred sixty-three patients from 42 centers across 24 cities in China were included.Epigastric pain(68.0%),abdominal distension(62.6%),and postprandial fullness(47.5%)were the most common presenting symptoms.Gastritis was classified as chronic non-atrophic in 69.9%of patients.Among those with erosive lesions,72.1%of patients had lesions in the antrum,51.0%had multiple lesions,and 67.3%had superficial flat lesions.In patients with epigastric pain,the combination of a mucosal protective agent(MPA)and proton pump inhibitor was more effective.For those with postprandial fullness,acid regurgitation,early satiety,or nausea,a MPA appeared more promising.CONCLUSION CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms.Gastroscopy may play a major role in its detection and diagnosis.Treatment should be individualized based on symptom profile.

Mitophagy in acute central nervous system injuries:regulatory mechanisms and therapeutic potentials

Acute central nervous system injuries,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,traumatic brain injury,and spinal co rd injury,are a major global health challenge.Identifying optimal therapies and improving the long-term neurological functions of patients with acute central nervous system injuries are urgent priorities.Mitochondria are susceptible to damage after acute central nervous system injury,and this leads to the release of toxic levels of reactive oxygen species,which induce cell death.Mitophagy,a selective form of autophagy,is crucial in eliminating redundant or damaged mitochondria during these events.Recent evidence has highlighted the significant role of mitophagy in acute central nervous system injuries.In this review,we provide a comprehensive overview of the process,classification,and related mechanisms of mitophagy.We also highlight the recent developments in research into the role of mitophagy in various acute central nervous system injuries and drug therapies that regulate mitophagy.In the final section of this review,we emphasize the potential for treating these disorders by focusing on mitophagy and suggest future research paths in this area.

Recombinant chitinase-3-like protein 1 alleviates learning and memory impairments via M2 microglia polarization in postoperative cognitive dysfunction mice

Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.

Preoperative controlling nutritional status as an optimal prognostic nutritional index to predict the outcome for colorectal cancer

BACKGROUND The controlling nutritional status(CONUT)score effectively reflects a patient’s nutritional status,which is closely related to cancer prognosis.This study invest-igated the relationship between the CONUT score and prognosis after radical surgery for colorectal cancer,and compared the predictive ability of the CONUT score with other indexes.AIM To analyze the predictive performance of the CONUT score for the survival rate of colorectal cancer patients who underwent potentially curative resection.METHODS This retrospective analysis included 217 patients with newly diagnosed colorectal.The CONUT score was calculated based on the serum albumin level,total lymphocyte count,and total cholesterol level.The cutoff value of the CONUT score for predicting prognosis was 4 according to the Youden Index by the receiver operating characteristic curve.The associations between the CONUT score and the prognosis were performed using Kaplan-Meier curves and Cox regression analysis.RESULTS Using the cutoff value of the CONUT score,patients were stratified into CONUT low(n=189)and CONUT high groups(n=28).The CONUT high group had worse overall survival(OS)(P=0.013)and relapse-free survival(RFS)(P=0.015).The predictive performance of CONUT was superior to the modified Glasgow prognostic score,the prognostic nutritional index,and the neutrophil-to-lymphocyte ratio.Meanwhile,the predictive performances of CONUT+tumor node metastasis(TNM)stage for 3-year OS[area under the receiver operating characteristics curve(AUC)=0.803]and 3-year RFS(AUC=0.752)were no less than skeletal muscle mass index(SMI)+TNM stage.The CONUT score was negatively correlated with SMI(P<0.01).CONCLUSION As a nutritional indicator,the CONUT score could predict long-term outcomes after radical surgery for colorectal cancer,and its predictive ability was superior to other indexes.The correlation between the CONUT score and skeletal muscle may be one of the factors that play a predictive role.

The diagnostic value of tenascin-C in acute aortic syndrome

OBJECTIVES Misdiagnosis of acute aortic syndrome(AAS)significantly increases mortality.Tenascin-C(TN-C)is an extracellular matrix glycoprotein related to cardiovascular injury.The elevation of TN-C in AAS and whether it can discriminate suddenonset of acute chest pain in Chinese remains unclear.METHODS We measured the plasma concentration of TN-C by ELISA in a cohort of 376 patients with chest or back pain.Measures to discriminate AAS from acute coronary syndrome(ACS)were compared and calculated.RESULTS From October 2016 to September 2021,376 undiagnosed patients with chest or back pain were enrolled.166 of them were finally diagnosed as AAS,100 were ACS and 110 without cardiovascular diseases(NCV).TN-C was significantly elevated in AAS at 18.18 ng/mL(IQR:13.10–27.68)compared with 7.51 ng/mL(IQR:5.67–11.38)in ACS(P<0.001)and 3.68 ng/mL(IQR:2.50–5.29)in NCV(P<0.001).There was no significant difference in TN-C level among the subtypes of AAS.Of the 166 AAS patients,the peaked level of TN-C was at acute stage(P=0.012),then a slight of decrease was observed at subacute stage.The area under receiver operating characteristic curve for AAS patients versus NCV was 0.979(95%CI:0.964-0.994)for TN-C.At a cutoff level of 11.474 ng/mL,TN-C has a sensitivity of 76.0%,specificity of 85.5%,accuracy of 82.0%,positive predictive value(PPV)of 76.0%,negative predictive value(NPV)of 85.5%.Diagnostic performance of TN-C was superior to D-dimer and hs-cTnT.CONCLUSIONS The concentration of serum TN-C in AAS patients was significantly higher than that in ACS patients and NCV.TN-C could be a new biomarker to distinguish AAS patients in the early stage after symptoms onset from other pain diseases.

Combined preoperative albumin bilirubin score and hepatectomy percentage for evaluate the liver regeneration after partial hepatectomy

Surgical resection is a pivotal therapeutic approach for addressing hepatic space-occupying lesions,with liver volume restoration and hepatic functional recovery being crucial for assessing surgical prognosis.The preoperative albumin-bilirubin(ALBI)score,encompassing serum albumin and bilirubin levels,can be determined via blood analysis,effectively mitigating human error and providing an accurate depiction of liver function.The hepatectomy ratio,which is the proportion of the liver volume removed to the total liver volume,is critical in preserving an adequate liver tissue volume to ensure postoperative hepatic functional compensation,minimize surgical complications,and reduce mortality rates.Incorporating the preoperative ALBI score and hepatectomy ratio aids surgeons in assessing the optimal timing and extent of partial hepatectomy.The introduction of preoperative albumin bilirubin score and hepatectomy percentage is beneficial for the surgeons to evaluate the timing and magnitude of partial liver resection.

Homozygous CCDC146 mutation causes oligoasthenoteratozoospermia in humans and mice

Infertility represents a significant health concern,with sperm quantity and quality being crucial determinants of male fertility.Oligoasthenoteratozoospermia(OAT)is characterized by reduced sperm motility,lower sperm concentration,and morphological abnormalities in sperm heads and flagella.Although variants in several genes have been implicated in OAT,its genetic etiologies and pathogenetic mechanisms remain inadequately understood.In this study,we identified a homozygous nonsense mutation(c.916C>T,p.Arg306*)in the coiled-coil domain containing 146(CCDC146)gene in an infertile male patient with OAT.This mutation resulted in the production of a truncated CCDC146 protein(amino acids 1-305),retaining only two out of five coiled-coil domains.To validate the pathogenicity of the CCDC146 mutation,we generated a mouse model(Ccdc146^(mut/mut))with a similar mutation to that of the patient.Consistently,the Ccdc146mut/mut mice exhibited infertility,characterized by significantly reduced sperm counts,diminished motility,and multiple defects in sperm heads and flagella.Furthermore,the levels of axonemal proteins,including DNAH17,DNAH1,and SPAG6,were significantly reduced in the sperm of Ccdc146^(mut/mut) mice.Additionally,both human and mouse CCDC146 interacted with intraflagellar transport protein 20(IFT20),but this interaction was lost in the mutated versions,leading to the degradation of IFT20.This study identified a novel deleterious homozygous nonsense mutation in CCDC146 that causes male infertility,potentially by disrupting axonemal protein transportation.These findings offer valuable insights for genetic counseling and understanding the mechanisms underlying CCDC146 mutant-associated infertility in human males.

Research progress of tumor-associated macrophages in immune checkpoint inhibitor tolerance in colorectal cancer

The relevant mechanism of tumor-associated macrophages(TAMs)in the treatment of colorectal cancer patients with immune checkpoint inhibitors(ICIs)is discussed,and the application prospects of TAMs in reversing the treatment tolerance of ICIs are discussed to provide a reference for related studies.As a class of drugs widely used in clinical tumor immunotherapy,ICIs can act on regulatory molecules on cells that play an inhibitory role-immune checkpoints-and kill tumors in the form of an immune response by activating a variety of immune cells in the immune system.The sensitivity of patients with different types of colorectal cancer to ICI treatment varies greatly.The phenotype and function of TAMs in the colorectal cancer microenvironment are closely related to the efficacy of ICIs.ICIs can regulate the phenotypic function of TAMs,and TAMs can also affect the tolerance of colorectal cancer to ICI therapy.TAMs play an important role in ICI resistance,and making full use of this target as a therapeutic strategy is expected to improve the immunotherapy efficacy and prognosis of patients with colorectal cancer.

Deep learning models semi-automatic training system for quality control of transthoracic echocardiography

Objective To explore the value of deep learning(DL)models semi-automatic training system for automatic optimization of clinical image quality control of transthoracic echocardiography(TTE).Methods Totally 1250 TTE videos from 402 patients were retrospectively collected,including 490 apical four chamber(A4C),310 parasternal long axis view of left ventricle(PLAX)and 450 parasternal short axis view of great vessel(PSAX GV).The videos were divided into development set(245 A4C,155 PLAX,225 PSAX GV),semi-automated training set(98 A4C,62 PLAX,90 PSAX GV)and test set(147 A4C,93 PLAX,135 PSAX GV)at the ratio of 5∶2∶3.Based on development set and semi-automatic training set,DL model of quality control was semi-automatically iteratively optimized,and a semi-automatic training system was constructed,then the efficacy of DL models for recognizing TTE views and assessing imaging quality of TTE were verified in test set.Results After optimization,the overall accuracy,precision,recall,and F1 score of DL models for recognizing TTE views in test set improved from 97.33%,97.26%,97.26%and 97.26%to 99.73%,99.65%,99.77%and 99.71%,respectively,while the overall accuracy for assessing A4C,PLAX and PSAX GV TTE as standard views in test set improved from 89.12%,83.87%and 90.37%to 93.20%,90.32%and 93.33%,respectively.Conclusion The developed DL models semi-automatic training system could improve the efficiency of clinical imaging quality control of TTE and increase iteration speed.

Application of sensory and motor training in AIDET communication mode in patients after knee arthroplasty

BACKGROUND Patients with knee arthroplasty often have problems such as slow recovery of knee function,which may cause negative emotions and affect their postoperative rehabilitation.The application of sensory and motor training in the Acknowledge,Introduce,Duration,Evaluation,Thank You(AIDET)communication mode in patients after knee arthroplasty can provide reference for the selection of postoperative rehabilitation training measures.AIM To explore the sensory and motor training effects in AIDET communication mode on knee function recovery and resilience of patients after knee arthroplasty.METHODS One hundred patients who underwent knee arthroplasty at our hospital between January 2022 and January 2024 were randomly divided into two groups.The control group(n=50)received routine rehabilitation training.In the observation group(n=50),the AIDET communication mode was used to perform sensory and motor training,in addition to routine rehabilitation training.The rehabilitation training was administered for 8 weeks.After surgery,knee function,balance ability,walking ability,proprioception,and resilience were compared between the two groups.RESULTS The New York Hospital for Special Surgery knee scores of the observation group at the time of discharge and 8 weeks after intervention were(65.23±6.84,84.53±5.27),which was higher than those of the control group(61.03±7.15,74.92±6.52)(P<0.05).The balance ability of the observation group at the time of discharge and 8 weeks after the intervention was higher than that of the control group,the time of time up to go test was shorter than that of the control group,and proprioceptive function was higher than that of the control group(P<0.05).The resilience level in the observation group after the intervention was higher than that in the control group(P<0.05).CONCLUSION Sensory and motor training in AIDET communication mode promotes knee function recovery of patients after knee arthroplasty,improves their limb walking ability and balance function,and increases their resilience level.

N-glycan biosignatures as a potential diagnostic biomarker for earlystage pancreatic cancer

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)has a poor prognosis,with a 5-year survival rate of less than 10%,owing to its late-stage diagnosis.Early detection of pancreatic cancer(PC)can significantly increase survival rates.AIM To identify the serum biomarker signatures associated with early-stage PDAC by serum N-glycan analysis.METHODS An extensive patient cohort was used to determine a biomarker signature,in-cluding patients with PDAC that was well-defined at an early stage(stages I and II).The biomarker signature was derived from a case-control study using a case-cohort design consisting of 29 patients with stage I,22 with stage II,4 with stage III,16 with stage IV PDAC,and 88 controls.We used multiparametric analysis to identify early-stage PDAC N-glycan signatures and developed an N-glycan sig-nature-based diagnosis model called the“Glyco-model”.RESULTS The biomarker signature was created to discriminate samples derived from patients with PC from those of controls,with a receiver operating characteristic area under the curve of 0.86.In addition,the biomarker signature combined with cancer antigen 19-9 could discriminate patients with PDAC from controls,with a receiver operating characteristic area under the curve of 0.919.Glyco-model demonstrated favorable diagnostic performance in all stages of PC.The diagnostic sensitivity for stage I PDAC was 89.66%.Core Tip:This study employed a patient cohort to investigate the N-glycan signature of early-stage pancreatic cancer(PC).Serum N-glycans analysis was conducted to identify the serum biomarker signature associated with early-stage pancreatic ductal adenocarcinoma(PDAC),resulting in the identification of nine early-stage PDAC N-glycan signatures.Subsequently,utilizing these biosignatures,a diagnostic model named the“Glyco-model”was developed,demonstrating promising diagnostic performance across all stages of PC.The study revealed that the diagnostic sensitivity for stage I PDAC was determined to be 89.66%.Consequently,this diagnostic model exhibits potential as a prospective strategy for the early detection of PDAC.

Acute liver failure:A clinically severe syndrome characterized by intricate mechanisms

Acute liver failure presents as a clinical syndrome characterized by swift deterioration and significant mortality rates.Its underlying mechanisms are intricate,involving intricate interplays between various cells.Given the current scarcity of treatment options,there's a pressing need to diligently uncover the disease's core mechanisms and administer targeted therapies accordingly.

Upregulation of α-ENaC induces pancreatic β-cell dysfunction,ER stress,and SIRT2 degradation

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.