BACKGROUND Knee osteoarthritis(KOA),a common disabling pathology characterized by knee joint pain,swelling,and functional impairment,primarily affects middle-aged and older adults.In addition to physical limitations,c...BACKGROUND Knee osteoarthritis(KOA),a common disabling pathology characterized by knee joint pain,swelling,and functional impairment,primarily affects middle-aged and older adults.In addition to physical limitations,chronic pain often leads to psychological problems,including anxiety and depression,which further impact patients’quality of life.AIM To examine the efficacy and safety of celecoxib plus duloxetine in managing chronic pain,anxiety,and depression in patients with KOA.METHODS A retrospective analysis was conducted on 123 patients with KOA treated at our center between February 2020 and February 2023.Of these,66 received celecoxib plus duloxetine,and 57 received celecoxib alone.Outcomes were assessed using the Visual Analog Scale(VAS),the Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC),and the Self-Rating Anxiety Scales(SAS)/Self-Rating Depression Scales(SDS).Safety was evaluated by monitoring changes in liver function enzymes(alanine aminotransferase,aspartate aminotransferase),creatinine,and blood urea nitrogen.RESULTS Patients receiving celecoxib plus duloxetine showed significantly greater reductions in VAS and WOMAC and greater improvements in SAS and SDS scores compared with those receiving celecoxib alone.Hepatorenal function did not differ significantly between the treatment groups.Logistic regression analysis identified patient age,educational background,and treatment regimen as independent predictors of inadequate improvement in negative emotional symptoms.CONCLUSION In patients with KOA,celecoxib plus duloxetine effectively mitigates chronic pain and improves anxiety and depressive symptoms without increasing adverse hepatic or renal effects.These findings support its use as a safe and effective treatment option.展开更多
BACKGROUND Anxiety,depression,and other negative emotions are common among patients with chronic renal failure(CRF).Analyzing the factors related to negative emotions is necessary to provide targeted nursing care.AIM ...BACKGROUND Anxiety,depression,and other negative emotions are common among patients with chronic renal failure(CRF).Analyzing the factors related to negative emotions is necessary to provide targeted nursing care.AIM To explore the correlations among life satisfaction,pleasure levels,and negative emotions in patients with CRF.METHODS One hundred patients with CRF who received therapy at the First Affiliated Hospital of Jinzhou Medical University between December 2022 and February 2025 were included.The Depression,Anxiety,and Stress Scale(DASS-21),Satisfaction with Life Scale(SWLS),and Temporal Experience of Pleasure Scale(TEPS)were used to evaluate negative emotions,life satisfaction,and pleasure level,respectively.Pearson’s correlation coefficient analyzed the correlation between life satisfaction,pleasure level,and negative emotions.Linear regression analysis identified the factors affecting negative emotions.RESULTS The average DASS-21 score among patients with CRF was 51.90±2.30,with subscale scores of 17.90±1.50 for depression,18.53±1.18 for anxiety,and 15.47±2.36 for stress,all significantly higher than the domestic norm(P<0.05).The average SWLS score was 22.17±4.90.Correlation analysis revealed a negative correlation between the SWLS and total DASS-21 scores(P<0.05),but not with the individual depression,anxiety,or stress dimensions.The average TEPS score was 67.80±8.34.TEPS scores were negatively correlated with the DASS-21 score and the stress dimension(P<0.05),but not with depression or anxiety.Linear regression analysis showed that TEPS scores significantly influenced DASS-21 scores(P<0.05).CONCLUSION Patients with CRF experience high levels of negative emotions,which are negatively correlated with life satisfaction and pleasure.Furthermore,pleasure level had an impact on negative emotions.展开更多
Myalgic encephalomyelitis/chronic fatigue syndrome-an insidious disease:The recent COVID-19 pandemic has brought substantial attention to the overlapping symptoms between long COVID and myalgic encephalomyelitis/chron...Myalgic encephalomyelitis/chronic fatigue syndrome-an insidious disease:The recent COVID-19 pandemic has brought substantial attention to the overlapping symptoms between long COVID and myalgic encephalomyelitis/chronic fatigue syndrome(ME/CFS),a chronic and poorly understood neurological disorder(Shankar et al.,2024).展开更多
Objective:To evaluate the effectiveness of direct-acting antivirals(DAAs)in patients with chronic hepatitis C,assess changes in liver function and hepatic fibrosis following treatment,and identify independent predicto...Objective:To evaluate the effectiveness of direct-acting antivirals(DAAs)in patients with chronic hepatitis C,assess changes in liver function and hepatic fibrosis following treatment,and identify independent predictors of treatment failure.Methods:This retrospective cohort study included patients who received DAA therapy at Hospital Kuala Lumpur between January 2020 and December 2023.Sustained virologic response(SVR)was assessed at least 12 weeks post-treatment by reverse transcription-polymerase chain reaction for hepatitis C virus(HCV)RNA.Demographic,clinical,and laboratory data were collected and analyzed.Multiple logistic regression analysis was performed to identify independent predictors of treatment failure.Results:A total of 335 patients in the study.The overall SVR rate was 89%.After achieving SVR,significant improvements were observed in liver enzyme levels and non-invasive liver fibrosis scores,whereas the overall Model for End-Stage Liver Disease(MELD)scores remained unchanged.Significant independent predictors of treatment failure included non-compliance with DAA therapy[adjusted odds ratio(aOR)68.3;95%confidence interval(95%CI)16.3-285.0;P<0.001],treatment with sofosbuvir/velpatasvir(aOR 6.1;95%CI 1.4-26.5;P=0.015),MELD score of 10-15(aOR 4.6;95%CI 1.1-18.2;P=0.031),HCV genotype 3 infection(aOR 4.5;95%CI 1.1-17.6;P=0.031),and elevated serum total bilirubin level(aOR 1.1;95%CI 1.0-1.1;P=0.003).Conclusions:DAA therapy yielded a high SVR rate,and treatment failure was strongly associated with non-adherence to therapy and advanced liver disease.These findings underscore the necessity of adherence support,early diagnosis,and individualized clinical management to optimize treatment outcomes in patients with chronic hepatitis C.展开更多
BACKGROUND Chronic atrophic gastritis(CAG)is a clinically refractory gastric disease often characterized by high recurrence rates and adverse drug reactions.Anwei decoction(AWD),a traditional Chinese medicine formula,...BACKGROUND Chronic atrophic gastritis(CAG)is a clinically refractory gastric disease often characterized by high recurrence rates and adverse drug reactions.Anwei decoction(AWD),a traditional Chinese medicine formula,has been shown to significantly improve clinical symptoms in patients with CAG,as demonstrated by a multicenter cohort study(overall effective rate:82.5%,P<0.01).However,the unclear molecular mechanisms and therapeutic targets of AWD limit its international acceptance.AIM To investigate the therapeutic mechanisms of AWD against CAG from an integrated perspective.METHODS In this study,N-methyl-N’-nitro-N-nitrosoguanidine was used to establish a CAG rat model.Serum-derived constituents transferred from AWD were first identified using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry.The concentrations of inflammatory cytokines in serum samples were determined by enzyme-linked immunosorbent assay.Moreover,gastric mucosal tissues were analyzed by quantitative realtime polymerase chain reaction to measure messenger RNA(mRNA)levels of the NLRP3 inflammasome.Western blotting was used to detect the protein expression of NLRP3,caspase-1,and interleukin(IL)-1β.To elucidate the regulatory mechanisms underlying AWD treatment,structural alterations of the gut microbiota(GM)and associated metabolites were analyzed using integrated high-throughput sequencing(16S rRNA)and liquid chromatography-mass spectrometry based untargeted metabolomics.This comprehensive approach systematically clarified AWD’s multi-target therapeutic mechanisms against CAG.RESULTS AWD notably reduced serum levels of pro-inflammatory cytokines,such as IL-1β,IL-18,tumor necrosis factor-α,and lipopolysaccharide,demonstrating significant statistical differences(all P<0.01).Additionally,AWD substantially inhibited NLRP3 mRNA expression in gastric mucosal tissue(P<0.01)and concurrently decreased the protein abundance of NLRP3,IL-1β,and caspase-1(all P<0.01),thereby suppressing inflammasome signaling activation.GM analysis indicated that AWD intervention significantly increased the relative abundance of beneficial bacteria.Associated microbial metabolites likely inhibited the NLRP3 inflammasome pathway by modulating immune cell function.Non-targeted metabolomics further indicated that AWD exerted anti-inflammatory effects by regulating critical metabolic pathways,including the Kaposi’s sarcoma-associated herpesvirus infection pathway,autophagy processes,and glycosylphosphatidylinositol-anchor biosynthesis.CONCLUSION AWD alleviates the pathological progression of CAG through multi-target synergistic mechanisms.On one hand,AWD directly suppresses gastric mucosal inflammation by inhibiting NLRP3 inflammasome activation.On the other hand,AWD remodels intestinal microbiota-metabolite homeostasis,enhances intestinal barrier function,and regulates mucosal immune responses.展开更多
Background:The development of gastric cancer(GC)encompasses precancerous conditions like chronic atrophic gastritis(CAG)and premalignant lesions of gastric cancer(PLGC).In these situations,abnormal Notch signaling res...Background:The development of gastric cancer(GC)encompasses precancerous conditions like chronic atrophic gastritis(CAG)and premalignant lesions of gastric cancer(PLGC).In these situations,abnormal Notch signaling results in mucosal impairment and the initiation of cancer.Banxia Xiexin Decoction(BXD),a well-known formula in traditional Chinese medicine(TCM),shows promise in treating gastric disorders,but its mechanisms in gastric restoration remain unclear.Methods:Using MNNG-induced CAG and PLGC rat models,BXD was administered for 12 weeks.Gastric mucosal pathology was assessed via hematoxylin-eosin staining.Proliferation(Ki-67)and angiogenesis(VEGFA)markers were evaluated by immunohistochemistry.Network pharmacology identified BXD’s targets and pathways.Notch pathway components(Notch1,Jagged1,Dll4,Hes1)were analyzed via qPCR,Western blot,and immunohistochemistry.Results:BXD significantly ameliorated mucosal atrophy,glandular structural disorder,and dysplasia in CAG and PLGC rats.Network pharmacology revealed 323 overlapping targets between BXD and PLGC,with Notch signaling as a central pathway.BXD downregulated Notch1,Jagged1,Dll4,and Hes1 expression at transcriptional and protein levels,suppressed Ki-67(proliferation)and VEGFA(angiogenesis)overexpression,and restored gastric mucosal integrity.Conclusion:BXD inhibits Notch signaling,reduces aberrant proliferation and angiogenesis,and interrupts Correa’s gastric carcinogenesis cascade.This study provides mechanistic evidence supporting BXD as a TCM-based intervention for gastric precancerous lesions.展开更多
Synaptic plasticity is essential for maintaining neuronal function in the central nervous system and serves as a critical indicator of the effects of neurodegenerative disease.Glaucoma directly impairs retinal ganglio...Synaptic plasticity is essential for maintaining neuronal function in the central nervous system and serves as a critical indicator of the effects of neurodegenerative disease.Glaucoma directly impairs retinal ganglion cells and their axons,leading to axonal transport dysfuntion,subsequently causing secondary damage to anterior or posterior ends of the visual system.Accordingly,recent evidence indicates that glaucoma is a degenerative disease of the central nervous system that causes damage throughout the visual pathway.However,the effects of glaucoma on synaptic plasticity in the primary visual cortex remain unclear.In this study,we established a mouse model of unilateral chronic ocular hypertension by injecting magnetic microbeads into the anterior chamber of one eye.We found that,after 4 weeks of chronic ocular hypertension,the neuronal somas were smaller in the superior colliculus and lateral geniculate body regions of the brain contralateral to the affected eye.This was accompanied by glial cell activation and increased expression of inflammatory factors.After 8 weeks of ocular hypertension,we observed a reduction in the number of excitatory and inhibitory synapses,dendritic spines,and activation of glial cells in the primary visual cortex contralateral to the affected eye.These findings suggest that glaucoma not only directly damages the retina but also induces alterations in synapses and dendritic spines in the primary visual cortex,providing new insights into the pathogenesis of glaucoma.展开更多
Background:Breakpoint Cluster Region-Abelson(BCR::ABL1)fusion protein is essential in the pathogenesis of chronic myeloid leukemia(CML);however,the chronic-to-blast phase transformation remains elusive.We identified n...Background:Breakpoint Cluster Region-Abelson(BCR::ABL1)fusion protein is essential in the pathogenesis of chronic myeloid leukemia(CML);however,the chronic-to-blast phase transformation remains elusive.We identified novel kinesin light chain 2(KLC2)mutations in CML-myeloid blast phase patients.We aimed to examine the functional role of KLC2 mutations in leukemogenesis.Methods:To evaluate the biological role of KLC2 mutants(MT)in CML cells,we expressed KLC2-MT in different human CML cell lines harboring BCR::ABL1 and performed immunoblot,immunofluorescence,cell proliferation,differentiation,and apoptosis;Tyrosine kinase inhibitor(TKI)-drug activities;and clonogenic assays for in vitro functional analyses.We co-expressed KLC2-MT and BCR::ABL1 in mouse bone marrow cells(BMCs)to evaluate their clonogenic and self-renewal abilities ex vivo.Furthermore,we examined tumorigenic activity and drug efficacy in the K562 xenograft model.Results:KLC2-MT overexpression in BCR::ABL1-positive K562 and KU812 CML cells promoted cell proliferation and clonogenic potential,decreased imatinib sensitivity,and reduced apoptosis.Serial colony replating assays revealed that KLC2-MT and BCR::ABL1 co-expression enhanced the self-renewal ability of mouse BMCs with immature morphology.In the K562 xenograft model,KLC2-MT enhanced tumorigenic potential and diminished imatinib efficacy.Further studies reported that KLC2-MT augmented signal transducer and activator of transcription 3(STAT3)activation and nuclear accumulation in imatinib-treated CML cells.KLC2-WT and KLC2-MT interacted with mothers against decapentaplegic homolog 2(SMAD2);however,the latter impaired transforming growth factor-beta(TGF-β)–mediated SMAD2/3 activation while enhancing STAT3 phosphorylation.Conclusions:This study demonstrates the biological and functional importance of KLC2 mutation in CML cells,potentially enabling the development of better treatment strategies for CML patients carrying KLC2 mutations and providing enhanced understanding of the disease progression.展开更多
Spinal cord injury is an intractable traumatic injury. The most common hurdles faced during spinal cord injury are failure of axonal regrowth and reconnection to target sites. These also tend to be the most challengin...Spinal cord injury is an intractable traumatic injury. The most common hurdles faced during spinal cord injury are failure of axonal regrowth and reconnection to target sites. These also tend to be the most challenging issues in spinal cord injury. As spinal cord injury progresses to the chronic phase, lost motor and sensory functions are not recovered. Several reasons may be attributed to the failure of recovery from chronic spinal cord injury. These include factors that inhibit axonal growth such as activated astrocytes, chondroitin sulfate proteoglycan, myelin-associated proteins, inflammatory microglia, and fibroblasts that accumulate at lesion sites. Skeletal muscle atrophy due to denervation is another chronic and detrimental spinal cord injury–specific condition. Although several intervention strategies based on multiple outlooks have been attempted for treating spinal cord injury, few approaches have been successful. To treat chronic spinal cord injury, neural cells or tissue substitutes may need to be supplied in the cavity area to enable possible axonal growth. Additionally, stimulating axonal growth activity by extrinsic factors is extremely important and essential for maintaining the remaining host neurons and transplanted neurons. This review focuses on pharmacotherapeutic approaches using small compounds and proteins to enable axonal growth in chronic spinal cord injury. This review presents some of these candidates that have shown promising outcomes in basic research(in vivo animal studies) and clinical trials: AA-NgR(310)ecto-Fc(AXER-204), fasudil, phosphatase and tensin homolog protein antagonist peptide 4, chondroitinase ABC, intracellular sigma peptide,(-)-epigallocatechin gallate, matrine, acteoside, pyrvate kinase M2, diosgenin, granulocyte-colony stimulating factor, and fampridine-sustained release. Although the current situation suggests that drug-based therapies to recover function in chronic spinal cord injury are limited, potential candidates have been identified through basic research, and these candidates may be subjects of clinical studies in the future. Moreover, cocktail therapy comprising drugs with varied underlying mechanisms may be effective in treating the refractory status of chronic spinal cord injury.展开更多
Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela ...Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.展开更多
In this editorial,we comment on the article by Meng et al.Chronic hepatitis B(CHB)is a significant global health problem,particularly in developing countries.Hepatitis B virus(HBV)infection is one of the most importan...In this editorial,we comment on the article by Meng et al.Chronic hepatitis B(CHB)is a significant global health problem,particularly in developing countries.Hepatitis B virus(HBV)infection is one of the most important risk factors for cirrhosis and hepatocellular carcinoma.Prevention and treatment of HBV are key measures to reduce complications.At present,drug therapy can effectively control virus replication and slow disease progression,but completely eliminating the virus remains a challenge.Anti-HBV treatment is a long-term process,and there are many kinds of antiviral drugs with different mechanisms of action,it is essential to evaluate the safety and efficacy of these drugs to reduce side effects and improve patients’compliance.We will summarize the current status of CHB drug treatment,hoping to provide a reference for the selection of clinical antiviral drugs.展开更多
BACKGROUND Colorectal polyps are commonly observed in patients with chronic liver disease(CLD)and pose a significant clinical concern because of their potential for malignancy.AIM To explore the clinical characteristi...BACKGROUND Colorectal polyps are commonly observed in patients with chronic liver disease(CLD)and pose a significant clinical concern because of their potential for malignancy.AIM To explore the clinical characteristics of colorectal polyps in patients with CLD,a nomogram was established to predict the presence of adenomatous polyps(AP).METHODS Patients with CLD who underwent colonoscopy at Tianjin Second People’s Hospital from January 2020 to May 2023 were evaluated.Clinical data including laboratory results,colonoscopy findings,and pathology reports were collected.Key variables for the nomogram were identified through least absolute shrinkage and selection operator regression,followed by multivariate logistic regression.The performance of the model was evaluated using the area under the receiver area under curve,as well as calibration curves and decision curve analysis.RESULTS The study enrolled 870 participants who underwent colonoscopy,and the detection rate of AP in patients with CLD was 28.6%.Compared to individuals without polyps,six risk factors were identified as predictors for AP occurrence:Age,male sex,body mass index,alcohol consumption,overlapping metabolic dysfunction-associated steatotic liver disease,and serum ferritin levels.The novel nomogram(AP model)demonstrated an area under curve of 0.801(95%confidence interval:0.756-0.845)and 0.785(95%confidence interval:0.712-0.858)in the training and validation groups.Calibration curves indicated good agreement among predicted and actual probabilities(training:χ^(2)=11.860,P=0.157;validation:χ^(2)=7.055,P=0.530).The decision curve analysis underscored the clinical utility of the nomogram for predicting the risk of AP.CONCLUSION The AP model showed reasonable accuracy and provided a clinical foundation for predicting the occurrence of AP in patients with CLD,which has a certain predictive value.展开更多
BACKGROUND Addressing the growing challenge of hospitalizing chronic multimorbid patients,this study examines the strain these conditions impose on healthcare systems at a local level,focusing on a pilot program.Chron...BACKGROUND Addressing the growing challenge of hospitalizing chronic multimorbid patients,this study examines the strain these conditions impose on healthcare systems at a local level,focusing on a pilot program.Chronic diseases and complex patients require comprehensive management strategies to reduce healthcare burdens and improve patient outcomes.If proven effective,this pilot model has the potential to be replicated in other healthcare settings to enhance the management of chronic multimorbid patients.AIM To evaluate the effectiveness of the high complexity unit(HCU)in managing chronic multimorbid patients through a multidisciplinary care model and to compare it with standard hospital care.METHODS The study employed a descriptive longitudinal approach,analyzing data from the Basic Minimum Data Set(BMDS)to compare hospitalization variables among the HCU,the Internal Medicine Service,and other services at Antequera Hospital throughout 2022.The HCU,designed for patients with complex chronic conditions,integrates a patient-centered model emphasizing multidisciplinary care and continuity post-discharge.RESULTS The study employed a descriptive longitudinal approach,analyzing data from the BMDS to compare hospitalization variables among the HCU,the Internal Medicine Service,and other services at Antequera Hospital throughout 2022.The HCU,designed for patients with complex chronic conditions,integrates a patient-centered model emphasizing multidisciplinary care and continuity post-discharge.CONCLUSION This study demonstrates the effectiveness of the HCU in managing patients with complex chronic diseases through a multidisciplinary approach.The coordinated care provided by the HCU results in improved patient outcomes,reduced unnecessary hospitalizations,and better management of patient complexity.The superiority of the HCU compared to standard care is evident in key outcomes such as fewer readmissions and higher patient satisfaction,reinforcing its value as a model of care to be replicated.展开更多
Lingguizhugan Decoction(LGZG)demonstrates significant efficacy in treating various cardiovascular diseases clinically,yet its precise mechanism of action remains elusive.This study aimed to elucidate the potential mec...Lingguizhugan Decoction(LGZG)demonstrates significant efficacy in treating various cardiovascular diseases clinically,yet its precise mechanism of action remains elusive.This study aimed to elucidate the potential mechanisms and effects of LGZG on isoproterenol(ISO)continuous stimulation-induced chronic heart failure(CHF)in mice,providing direct experimental evidence for further clinical applications.In vivo,continuous ISO infusion was administered to mice,and ventricular myocytes were utilized to explore LGZG's potential mechanism of action on theβ1-adrenergic receptor(β1-AR)/Gs/G protein-coupled receptor kinases(GRKs)/β-arrestin signaling deflection system in the heart.The findings reveal that LGZG significantly reduced the messenger ribonucleic acid(mRNA)expression of hypertrophy-related biomarkers[atrial natriuretic peptide(ANP)and B-type natriuretic peptide(BNP)]and improved cardiac remodeling and left ventricular diastolic function in mice with ISO-induced CHF.Furthermore,LGZG inhibited the overactivation of Gs/cyclic adenosine monophosphate(c AMP)/protein kinase A(PKA)signaling and downregulated the downstream transcriptional activity of c AMP-response element binding protein(CREB)and the expression of the coactivator CBP/P300.Notably,LGZG downregulated the expression ofβ-arrestin1 and GRK 2/3/5 while upregulating the expression ofβ1-AR andβ-arrestin2.These results suggest that LGZG inhibits Gs/c AMP/PKA signaling andβ-arrestin/GRK-mediated desensitization and internalization ofβ1-AR,potentially exerting cardioprotective effects through the synergistic regulation of theβ1-AR/Gs/GRKs/β-arrestin signaling deflection system via multiple pathways.展开更多
Chronic atrophic gastritis(CAG)is an important stage of precancerous lesions of gastric cancer.Effective treatment and regulation of CAG are essential to prevent its progression to malignancy.Traditional Chinese medic...Chronic atrophic gastritis(CAG)is an important stage of precancerous lesions of gastric cancer.Effective treatment and regulation of CAG are essential to prevent its progression to malignancy.Traditional Chinese medicine(TCM)has shown multi-targeted efficacy in CAG treatment,with advantages in enhancing gastric mucosal barrier defense,improving microcirculation,modulating inflammatory and immune responses,and promoting lesion healing,etc.Clinical studies and meta-analyses indicate that TCM provides significant benefits,with specific Chinese herbal compounds and monomers demonstrating protective effects on the gastric mucosa through mechanisms including anti-inflammation,antioxidation,and regulation of cellular proliferation and apoptosis,etc.Finally,it is pointed out that the efficacy of TCM in the treatment of CAG requires standardized research and unified standards,and constantly clarifies and improves the evaluation criteria of each dimension of gastric mucosal barrier function.展开更多
Objective:To investigate the clinical efficacy of levofloxacin combined with ambroxol in the treatment of elderly patients with chronic obstructive pulmonary disease(COPD)and pulmonary infection.Methods:A total of 80 ...Objective:To investigate the clinical efficacy of levofloxacin combined with ambroxol in the treatment of elderly patients with chronic obstructive pulmonary disease(COPD)and pulmonary infection.Methods:A total of 80 elderly COPD patients with pulmonary infection,treated between December 2022 and November 2023,were randomly divided into a control group and an observation group,with 40 cases in each group.The control group was treated with levofloxacin hydrochloride,while the observation group received ambroxol hydrochloride injection in addition to the treatment in the control group.Laboratory indices(white blood cell count,procalcitonin,C-reactive protein,and apolipoprotein E levels),imaging-based pulmonary lesion absorption time,hospital stay,and incidence of adverse reactions were compared between the two groups.Results:After treatment,the biochemical indices of the observation group were significantly lower than those of the control group,with highly significant differences(P<0.001).Compared to the control group,the imaging-based pulmonary lesion absorption time and hospital stay of the observation group were significantly shorter(P<0.001).Additionally,the incidence of adverse reactions in the observation group was significantly lower than in the control group(P<0.05).Conclusion:Levofloxacin combined with ambroxol demonstrates advantages in improving biochemical indices,shortening imaging-based pulmonary lesion absorption time and hospital stay,and reducing adverse reaction rates in elderly COPD patients with pulmonary infection.It holds significant clinical application value.展开更多
BACKGROUND Middle meningeal artery embolization(MMAE)is emerging as a promising treatment for chronic subdural hematoma(CSDH),serving both as an adjunct to surgery and as a primary therapeutic option depending on pati...BACKGROUND Middle meningeal artery embolization(MMAE)is emerging as a promising treatment for chronic subdural hematoma(CSDH),serving both as an adjunct to surgery and as a primary therapeutic option depending on patient presentation.Due to its low recurrence rate and minimal complications,MMAE has gained increasing acceptance among clinicians in recent years.This report presents a case of diplopia following MMAE due to the presence of a potential anastomotic artery,aiming to enhance awareness of this complication.CASE SUMMARY A 60-year-old male patient presented with a headache following head trauma,and cranial computed tomography revealed a left-sided CSDH.The patient underwent left MMAE;however,polyvinyl alcohol particles inadvertently flowed into the lacrimal artery through an anastomotic artery,resulting in diplopia due to impaired abduction of the left eye.The diplopia resolved by postoperative day 40.The patient’s headache resolved by postoperative day 7,and the hematoma completely resolved by postoperative day 108.CONCLUSION Potential anastomotic arteries in the middle meningeal artery(MMA)can lead to serious complications.Superselective angiography of the MMA or its branches prior to embolization is essential.Performing embolization distal to potential anastomotic sites can reduce risks,and the presence of an anastomosis may warrant coil embolization or termination of the procedure.展开更多
BACKGROUND In diabetic patients,persistent hyperglycemia creates an optimal environment for the proliferation of pathogenic bacteria,resulting in severe complications.Con-sequently,chronic rhinosinusitis(CRS)complicat...BACKGROUND In diabetic patients,persistent hyperglycemia creates an optimal environment for the proliferation of pathogenic bacteria,resulting in severe complications.Con-sequently,chronic rhinosinusitis(CRS)complicated by diabetes is highly pre-valent in clinical settings.AIM To analyze the results of nasal secretion cultures in diabetic patients with CRS and identify the factors influencing postoperative recurrence.METHODS A retrospective analysis was conducted on the clinical data of 203 diabetic pa-tients with CRS with nasal polyps who underwent the Messerklinger technique at Qingdao Hiser Hospital Affiliated of Qingdao University between January 2021 and January 2023.Preoperative nasal secretions were cultured to determine the types and distribution of pathogenic bacteria and assess antimicrobial suscept-ibility.Based on a one-year follow-up,patients were categorized into recurrence and nonrecurrence groups to analyze differences in their clinical data.Univariate and multivariate analyses were used to identify factors influencing postoperative recurrence.RESULTS Pathogens were detected in 153 of the 203 nasal secretion specimens collected from diabetic patients with CRS.A total of 134 pathogenic bacteria strains were isolated and identified,including 81 strains(60.4%)of gram-positive bacteria and 53 strains(39.6%)of gram-negative bacteria.Gram-positive bacteria exhibited relatively high resistance to penicillin G and erythromycin,while remaining highly sensitive to vancomycin,gentamicin,and rifampicin.Gram-negative bacteria demonstrated relatively high resistance to cefazolin and gentamicin,but showed high sensitivity to imipenem,meropenem,cefepime,and ceftazidime.Univariate analysis revealed statistically significant differences between the recurrence and nonrecurrence groups in fasting blood glucose levels,smoking history,Lund-Mackay scores,visual analog scale(VAS)scores,nasal septum deviation,allergic rhinitis,bronchial asthma,postoperative infection,long-term use of nasal decongestants,and adherence to medical prescriptions.Multivariate regression analysis identified fasting blood glucose levels and VAS-measured nasal symptom severity scores as independent factors influencing postoperative recurrence.CONCLUSION In CRS patients with nasal polyps(CRSwNP),the detection rate of nasal pathogens is relatively high,and most of the isolated bacteria exhibit antimicrobial resistance.Additionally,the blood glucose level of patients with CRS combined with CRSwNP is a risk factor for postoperative recurrence.展开更多
BACKGROUND Anxiety and depression are prevalent among patients with chronic heart failure(CHF)and can adversely contribute to treatment adherence and clinical outcomes.Poor fluid restriction adherence is a widespread ...BACKGROUND Anxiety and depression are prevalent among patients with chronic heart failure(CHF)and can adversely contribute to treatment adherence and clinical outcomes.Poor fluid restriction adherence is a widespread challenge in the management of CHF.To effectively manage disease progression and alleviate symptoms,it is crucial to identify key influencing factors to facilitate the implementation of targeted interventions.AIM To investigate the status of anxiety and depression among patients with CHF and determine the factors contributing to poor fluid restriction adherence.METHODS Three hundred CHF patients seeking medical treatment at The First Hospital of Hunan University of Traditional Chinese Medicine between June 2021 and June 2023 were included in the study.Questionnaires,including the Psychosomatic Symptom Scale,Self-Rating Anxiety Scale,Self-Rating Depression Scale,and Fluid Restriction Adherence Questionnaire were administered to patients.Based on their anxiety and depression scores,patients were categorized into anxiety/depression and non-anxiety/depression groups,as well as fluid restriction adherence and fluid restriction non-adherence groups.General patient data were collected,and univariate and logistic regression analyses were conducted to determine the occurrence of depression and anxiety.Logistic regression analysis was used to identify independent factors influencing fluid restriction adherence.RESULTS Statistically significant differences in age,New York Heart Association(NYHA)grading,marital status,educational attainment,and family support were observed between depressed and non-depressed CHF patients(P<0.05).Age,NYHA grading,marital status,educational attainment,and family support were identified as factors influencing the development of depression.The anxiety and non-anxiety groups differed statistically in terms of gender,age,NYHA grading,smoking history,alcohol consumption history,monthly income,educational attainment,and family support(P<0.05).Gender,smoking,alcohol consumption,monthly income,and educational attainment affected anxiety in these patients.The fluid restriction adherence rate was 28.0%,and thirst sensation,anxiety,and depression were identified as independent influencing factors.CONCLUSION CHF patients are susceptible to anxiety and depression,with multiple associated influencing factors.Moreover,anxiety and depression are independent factors that can influence fluid restriction adherence in these patients.展开更多
文摘BACKGROUND Knee osteoarthritis(KOA),a common disabling pathology characterized by knee joint pain,swelling,and functional impairment,primarily affects middle-aged and older adults.In addition to physical limitations,chronic pain often leads to psychological problems,including anxiety and depression,which further impact patients’quality of life.AIM To examine the efficacy and safety of celecoxib plus duloxetine in managing chronic pain,anxiety,and depression in patients with KOA.METHODS A retrospective analysis was conducted on 123 patients with KOA treated at our center between February 2020 and February 2023.Of these,66 received celecoxib plus duloxetine,and 57 received celecoxib alone.Outcomes were assessed using the Visual Analog Scale(VAS),the Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC),and the Self-Rating Anxiety Scales(SAS)/Self-Rating Depression Scales(SDS).Safety was evaluated by monitoring changes in liver function enzymes(alanine aminotransferase,aspartate aminotransferase),creatinine,and blood urea nitrogen.RESULTS Patients receiving celecoxib plus duloxetine showed significantly greater reductions in VAS and WOMAC and greater improvements in SAS and SDS scores compared with those receiving celecoxib alone.Hepatorenal function did not differ significantly between the treatment groups.Logistic regression analysis identified patient age,educational background,and treatment regimen as independent predictors of inadequate improvement in negative emotional symptoms.CONCLUSION In patients with KOA,celecoxib plus duloxetine effectively mitigates chronic pain and improves anxiety and depressive symptoms without increasing adverse hepatic or renal effects.These findings support its use as a safe and effective treatment option.
文摘BACKGROUND Anxiety,depression,and other negative emotions are common among patients with chronic renal failure(CRF).Analyzing the factors related to negative emotions is necessary to provide targeted nursing care.AIM To explore the correlations among life satisfaction,pleasure levels,and negative emotions in patients with CRF.METHODS One hundred patients with CRF who received therapy at the First Affiliated Hospital of Jinzhou Medical University between December 2022 and February 2025 were included.The Depression,Anxiety,and Stress Scale(DASS-21),Satisfaction with Life Scale(SWLS),and Temporal Experience of Pleasure Scale(TEPS)were used to evaluate negative emotions,life satisfaction,and pleasure level,respectively.Pearson’s correlation coefficient analyzed the correlation between life satisfaction,pleasure level,and negative emotions.Linear regression analysis identified the factors affecting negative emotions.RESULTS The average DASS-21 score among patients with CRF was 51.90±2.30,with subscale scores of 17.90±1.50 for depression,18.53±1.18 for anxiety,and 15.47±2.36 for stress,all significantly higher than the domestic norm(P<0.05).The average SWLS score was 22.17±4.90.Correlation analysis revealed a negative correlation between the SWLS and total DASS-21 scores(P<0.05),but not with the individual depression,anxiety,or stress dimensions.The average TEPS score was 67.80±8.34.TEPS scores were negatively correlated with the DASS-21 score and the stress dimension(P<0.05),but not with depression or anxiety.Linear regression analysis showed that TEPS scores significantly influenced DASS-21 scores(P<0.05).CONCLUSION Patients with CRF experience high levels of negative emotions,which are negatively correlated with life satisfaction and pleasure.Furthermore,pleasure level had an impact on negative emotions.
基金supported by the Judith Jane Mason and Harold Stannett Williams Memorial Foundation National Medical Program(#Mason2210)to JX。
文摘Myalgic encephalomyelitis/chronic fatigue syndrome-an insidious disease:The recent COVID-19 pandemic has brought substantial attention to the overlapping symptoms between long COVID and myalgic encephalomyelitis/chronic fatigue syndrome(ME/CFS),a chronic and poorly understood neurological disorder(Shankar et al.,2024).
文摘Objective:To evaluate the effectiveness of direct-acting antivirals(DAAs)in patients with chronic hepatitis C,assess changes in liver function and hepatic fibrosis following treatment,and identify independent predictors of treatment failure.Methods:This retrospective cohort study included patients who received DAA therapy at Hospital Kuala Lumpur between January 2020 and December 2023.Sustained virologic response(SVR)was assessed at least 12 weeks post-treatment by reverse transcription-polymerase chain reaction for hepatitis C virus(HCV)RNA.Demographic,clinical,and laboratory data were collected and analyzed.Multiple logistic regression analysis was performed to identify independent predictors of treatment failure.Results:A total of 335 patients in the study.The overall SVR rate was 89%.After achieving SVR,significant improvements were observed in liver enzyme levels and non-invasive liver fibrosis scores,whereas the overall Model for End-Stage Liver Disease(MELD)scores remained unchanged.Significant independent predictors of treatment failure included non-compliance with DAA therapy[adjusted odds ratio(aOR)68.3;95%confidence interval(95%CI)16.3-285.0;P<0.001],treatment with sofosbuvir/velpatasvir(aOR 6.1;95%CI 1.4-26.5;P=0.015),MELD score of 10-15(aOR 4.6;95%CI 1.1-18.2;P=0.031),HCV genotype 3 infection(aOR 4.5;95%CI 1.1-17.6;P=0.031),and elevated serum total bilirubin level(aOR 1.1;95%CI 1.0-1.1;P=0.003).Conclusions:DAA therapy yielded a high SVR rate,and treatment failure was strongly associated with non-adherence to therapy and advanced liver disease.These findings underscore the necessity of adherence support,early diagnosis,and individualized clinical management to optimize treatment outcomes in patients with chronic hepatitis C.
基金Supported by the National Natural Science Foundation of China,No.81860843Guangxi Administration of Traditional Chinese Medicine Project,No.GZSY23-36 and No.GXZYA20240150。
文摘BACKGROUND Chronic atrophic gastritis(CAG)is a clinically refractory gastric disease often characterized by high recurrence rates and adverse drug reactions.Anwei decoction(AWD),a traditional Chinese medicine formula,has been shown to significantly improve clinical symptoms in patients with CAG,as demonstrated by a multicenter cohort study(overall effective rate:82.5%,P<0.01).However,the unclear molecular mechanisms and therapeutic targets of AWD limit its international acceptance.AIM To investigate the therapeutic mechanisms of AWD against CAG from an integrated perspective.METHODS In this study,N-methyl-N’-nitro-N-nitrosoguanidine was used to establish a CAG rat model.Serum-derived constituents transferred from AWD were first identified using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry.The concentrations of inflammatory cytokines in serum samples were determined by enzyme-linked immunosorbent assay.Moreover,gastric mucosal tissues were analyzed by quantitative realtime polymerase chain reaction to measure messenger RNA(mRNA)levels of the NLRP3 inflammasome.Western blotting was used to detect the protein expression of NLRP3,caspase-1,and interleukin(IL)-1β.To elucidate the regulatory mechanisms underlying AWD treatment,structural alterations of the gut microbiota(GM)and associated metabolites were analyzed using integrated high-throughput sequencing(16S rRNA)and liquid chromatography-mass spectrometry based untargeted metabolomics.This comprehensive approach systematically clarified AWD’s multi-target therapeutic mechanisms against CAG.RESULTS AWD notably reduced serum levels of pro-inflammatory cytokines,such as IL-1β,IL-18,tumor necrosis factor-α,and lipopolysaccharide,demonstrating significant statistical differences(all P<0.01).Additionally,AWD substantially inhibited NLRP3 mRNA expression in gastric mucosal tissue(P<0.01)and concurrently decreased the protein abundance of NLRP3,IL-1β,and caspase-1(all P<0.01),thereby suppressing inflammasome signaling activation.GM analysis indicated that AWD intervention significantly increased the relative abundance of beneficial bacteria.Associated microbial metabolites likely inhibited the NLRP3 inflammasome pathway by modulating immune cell function.Non-targeted metabolomics further indicated that AWD exerted anti-inflammatory effects by regulating critical metabolic pathways,including the Kaposi’s sarcoma-associated herpesvirus infection pathway,autophagy processes,and glycosylphosphatidylinositol-anchor biosynthesis.CONCLUSION AWD alleviates the pathological progression of CAG through multi-target synergistic mechanisms.On one hand,AWD directly suppresses gastric mucosal inflammation by inhibiting NLRP3 inflammasome activation.On the other hand,AWD remodels intestinal microbiota-metabolite homeostasis,enhances intestinal barrier function,and regulates mucosal immune responses.
基金supported by a grant from NIH(R01AI132695)to RM。
文摘Chronic wasting disease—a prion disease affecting cervids:Many neurological conditions,including Alzheimer's and Parkinson's diseases,amyotrophic lateral sclerosis,frontotemporal dementias,among others,are caused by the accumulation of misfolded proteins in the brain.These diseases affect not only humans,but also animals.
基金supported by the National Natural Science Foundation of China(Grant No.82274442)the Key Research Project in Traditional Chinese Medicine of Tianjin Municipal Health Commission(Grant No.202007)the Integrated Traditional Chinese and Western Medicine Research Project of Tianjin Municipal Health Commission(Grant No.2023134).
文摘Background:The development of gastric cancer(GC)encompasses precancerous conditions like chronic atrophic gastritis(CAG)and premalignant lesions of gastric cancer(PLGC).In these situations,abnormal Notch signaling results in mucosal impairment and the initiation of cancer.Banxia Xiexin Decoction(BXD),a well-known formula in traditional Chinese medicine(TCM),shows promise in treating gastric disorders,but its mechanisms in gastric restoration remain unclear.Methods:Using MNNG-induced CAG and PLGC rat models,BXD was administered for 12 weeks.Gastric mucosal pathology was assessed via hematoxylin-eosin staining.Proliferation(Ki-67)and angiogenesis(VEGFA)markers were evaluated by immunohistochemistry.Network pharmacology identified BXD’s targets and pathways.Notch pathway components(Notch1,Jagged1,Dll4,Hes1)were analyzed via qPCR,Western blot,and immunohistochemistry.Results:BXD significantly ameliorated mucosal atrophy,glandular structural disorder,and dysplasia in CAG and PLGC rats.Network pharmacology revealed 323 overlapping targets between BXD and PLGC,with Notch signaling as a central pathway.BXD downregulated Notch1,Jagged1,Dll4,and Hes1 expression at transcriptional and protein levels,suppressed Ki-67(proliferation)and VEGFA(angiogenesis)overexpression,and restored gastric mucosal integrity.Conclusion:BXD inhibits Notch signaling,reduces aberrant proliferation and angiogenesis,and interrupts Correa’s gastric carcinogenesis cascade.This study provides mechanistic evidence supporting BXD as a TCM-based intervention for gastric precancerous lesions.
基金supported by the National Natural Science Foundation of China,No.82271115(to MY).
文摘Synaptic plasticity is essential for maintaining neuronal function in the central nervous system and serves as a critical indicator of the effects of neurodegenerative disease.Glaucoma directly impairs retinal ganglion cells and their axons,leading to axonal transport dysfuntion,subsequently causing secondary damage to anterior or posterior ends of the visual system.Accordingly,recent evidence indicates that glaucoma is a degenerative disease of the central nervous system that causes damage throughout the visual pathway.However,the effects of glaucoma on synaptic plasticity in the primary visual cortex remain unclear.In this study,we established a mouse model of unilateral chronic ocular hypertension by injecting magnetic microbeads into the anterior chamber of one eye.We found that,after 4 weeks of chronic ocular hypertension,the neuronal somas were smaller in the superior colliculus and lateral geniculate body regions of the brain contralateral to the affected eye.This was accompanied by glial cell activation and increased expression of inflammatory factors.After 8 weeks of ocular hypertension,we observed a reduction in the number of excitatory and inhibitory synapses,dendritic spines,and activation of glial cells in the primary visual cortex contralateral to the affected eye.These findings suggest that glaucoma not only directly damages the retina but also induces alterations in synapses and dendritic spines in the primary visual cortex,providing new insights into the pathogenesis of glaucoma.
基金supported by grants from the Ministry of Science and Technology,Taiwan(MOST108-2314-B-182-006,MOST109-2314-B-182-071:Lee-Yung Shih)the Ministry of Health and Welfare,Taiwan(MOHW110-TDU-B-212-134011:Lee-Yung Shih)+3 种基金Chang Gung Memorial Hospital(CMRPG3D1524,OMRPG3E0031:Lee-Yung Shih)the Grant-in-Aid for the Japan Society for the Promotion of Science(JSPS)KAKENHI(JP19H05656:Seishi Ogawa,22K16320:Yotaro Ochi)the Japan Agency for Medical Research and Development(AMED)(JP19cm0106501h0004,JP19ck0106250h0003:Seishi Ogawa)the Ministry of Education,Culture,Sports,Science and Technology of Japan(MEXT)(hp200138,hp210167:Seishi Ogawa)。
文摘Background:Breakpoint Cluster Region-Abelson(BCR::ABL1)fusion protein is essential in the pathogenesis of chronic myeloid leukemia(CML);however,the chronic-to-blast phase transformation remains elusive.We identified novel kinesin light chain 2(KLC2)mutations in CML-myeloid blast phase patients.We aimed to examine the functional role of KLC2 mutations in leukemogenesis.Methods:To evaluate the biological role of KLC2 mutants(MT)in CML cells,we expressed KLC2-MT in different human CML cell lines harboring BCR::ABL1 and performed immunoblot,immunofluorescence,cell proliferation,differentiation,and apoptosis;Tyrosine kinase inhibitor(TKI)-drug activities;and clonogenic assays for in vitro functional analyses.We co-expressed KLC2-MT and BCR::ABL1 in mouse bone marrow cells(BMCs)to evaluate their clonogenic and self-renewal abilities ex vivo.Furthermore,we examined tumorigenic activity and drug efficacy in the K562 xenograft model.Results:KLC2-MT overexpression in BCR::ABL1-positive K562 and KU812 CML cells promoted cell proliferation and clonogenic potential,decreased imatinib sensitivity,and reduced apoptosis.Serial colony replating assays revealed that KLC2-MT and BCR::ABL1 co-expression enhanced the self-renewal ability of mouse BMCs with immature morphology.In the K562 xenograft model,KLC2-MT enhanced tumorigenic potential and diminished imatinib efficacy.Further studies reported that KLC2-MT augmented signal transducer and activator of transcription 3(STAT3)activation and nuclear accumulation in imatinib-treated CML cells.KLC2-WT and KLC2-MT interacted with mothers against decapentaplegic homolog 2(SMAD2);however,the latter impaired transforming growth factor-beta(TGF-β)–mediated SMAD2/3 activation while enhancing STAT3 phosphorylation.Conclusions:This study demonstrates the biological and functional importance of KLC2 mutation in CML cells,potentially enabling the development of better treatment strategies for CML patients carrying KLC2 mutations and providing enhanced understanding of the disease progression.
文摘Spinal cord injury is an intractable traumatic injury. The most common hurdles faced during spinal cord injury are failure of axonal regrowth and reconnection to target sites. These also tend to be the most challenging issues in spinal cord injury. As spinal cord injury progresses to the chronic phase, lost motor and sensory functions are not recovered. Several reasons may be attributed to the failure of recovery from chronic spinal cord injury. These include factors that inhibit axonal growth such as activated astrocytes, chondroitin sulfate proteoglycan, myelin-associated proteins, inflammatory microglia, and fibroblasts that accumulate at lesion sites. Skeletal muscle atrophy due to denervation is another chronic and detrimental spinal cord injury–specific condition. Although several intervention strategies based on multiple outlooks have been attempted for treating spinal cord injury, few approaches have been successful. To treat chronic spinal cord injury, neural cells or tissue substitutes may need to be supplied in the cavity area to enable possible axonal growth. Additionally, stimulating axonal growth activity by extrinsic factors is extremely important and essential for maintaining the remaining host neurons and transplanted neurons. This review focuses on pharmacotherapeutic approaches using small compounds and proteins to enable axonal growth in chronic spinal cord injury. This review presents some of these candidates that have shown promising outcomes in basic research(in vivo animal studies) and clinical trials: AA-NgR(310)ecto-Fc(AXER-204), fasudil, phosphatase and tensin homolog protein antagonist peptide 4, chondroitinase ABC, intracellular sigma peptide,(-)-epigallocatechin gallate, matrine, acteoside, pyrvate kinase M2, diosgenin, granulocyte-colony stimulating factor, and fampridine-sustained release. Although the current situation suggests that drug-based therapies to recover function in chronic spinal cord injury are limited, potential candidates have been identified through basic research, and these candidates may be subjects of clinical studies in the future. Moreover, cocktail therapy comprising drugs with varied underlying mechanisms may be effective in treating the refractory status of chronic spinal cord injury.
文摘Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.
基金Supported by the Project of Guizhou Provincial Department of Science and Technology,No.Qiankehechengguo-LC[2024]109.
文摘In this editorial,we comment on the article by Meng et al.Chronic hepatitis B(CHB)is a significant global health problem,particularly in developing countries.Hepatitis B virus(HBV)infection is one of the most important risk factors for cirrhosis and hepatocellular carcinoma.Prevention and treatment of HBV are key measures to reduce complications.At present,drug therapy can effectively control virus replication and slow disease progression,but completely eliminating the virus remains a challenge.Anti-HBV treatment is a long-term process,and there are many kinds of antiviral drugs with different mechanisms of action,it is essential to evaluate the safety and efficacy of these drugs to reduce side effects and improve patients’compliance.We will summarize the current status of CHB drug treatment,hoping to provide a reference for the selection of clinical antiviral drugs.
基金Supported by the National Natural Science Foundation of China,No.62375202Natural Science Foundation of Tianjin,No.23JCYBJC00950+1 种基金Tianjin Health Science and Technology Project Key Discipline Special,No.TJWJ2022XK034Research Project in Key Areas of Traditional Chinese Medicine in 2024,No.2024022.
文摘BACKGROUND Colorectal polyps are commonly observed in patients with chronic liver disease(CLD)and pose a significant clinical concern because of their potential for malignancy.AIM To explore the clinical characteristics of colorectal polyps in patients with CLD,a nomogram was established to predict the presence of adenomatous polyps(AP).METHODS Patients with CLD who underwent colonoscopy at Tianjin Second People’s Hospital from January 2020 to May 2023 were evaluated.Clinical data including laboratory results,colonoscopy findings,and pathology reports were collected.Key variables for the nomogram were identified through least absolute shrinkage and selection operator regression,followed by multivariate logistic regression.The performance of the model was evaluated using the area under the receiver area under curve,as well as calibration curves and decision curve analysis.RESULTS The study enrolled 870 participants who underwent colonoscopy,and the detection rate of AP in patients with CLD was 28.6%.Compared to individuals without polyps,six risk factors were identified as predictors for AP occurrence:Age,male sex,body mass index,alcohol consumption,overlapping metabolic dysfunction-associated steatotic liver disease,and serum ferritin levels.The novel nomogram(AP model)demonstrated an area under curve of 0.801(95%confidence interval:0.756-0.845)and 0.785(95%confidence interval:0.712-0.858)in the training and validation groups.Calibration curves indicated good agreement among predicted and actual probabilities(training:χ^(2)=11.860,P=0.157;validation:χ^(2)=7.055,P=0.530).The decision curve analysis underscored the clinical utility of the nomogram for predicting the risk of AP.CONCLUSION The AP model showed reasonable accuracy and provided a clinical foundation for predicting the occurrence of AP in patients with CLD,which has a certain predictive value.
基金Supported by Fundación Progreso y Salud,No.AP-0306-2022-C3-F2.
文摘BACKGROUND Addressing the growing challenge of hospitalizing chronic multimorbid patients,this study examines the strain these conditions impose on healthcare systems at a local level,focusing on a pilot program.Chronic diseases and complex patients require comprehensive management strategies to reduce healthcare burdens and improve patient outcomes.If proven effective,this pilot model has the potential to be replicated in other healthcare settings to enhance the management of chronic multimorbid patients.AIM To evaluate the effectiveness of the high complexity unit(HCU)in managing chronic multimorbid patients through a multidisciplinary care model and to compare it with standard hospital care.METHODS The study employed a descriptive longitudinal approach,analyzing data from the Basic Minimum Data Set(BMDS)to compare hospitalization variables among the HCU,the Internal Medicine Service,and other services at Antequera Hospital throughout 2022.The HCU,designed for patients with complex chronic conditions,integrates a patient-centered model emphasizing multidisciplinary care and continuity post-discharge.RESULTS The study employed a descriptive longitudinal approach,analyzing data from the BMDS to compare hospitalization variables among the HCU,the Internal Medicine Service,and other services at Antequera Hospital throughout 2022.The HCU,designed for patients with complex chronic conditions,integrates a patient-centered model emphasizing multidisciplinary care and continuity post-discharge.CONCLUSION This study demonstrates the effectiveness of the HCU in managing patients with complex chronic diseases through a multidisciplinary approach.The coordinated care provided by the HCU results in improved patient outcomes,reduced unnecessary hospitalizations,and better management of patient complexity.The superiority of the HCU compared to standard care is evident in key outcomes such as fewer readmissions and higher patient satisfaction,reinforcing its value as a model of care to be replicated.
基金supported by the National Natural Science Foundation of China(No.82074054)Shanghai Municipal Commission of Health and Family Planning(No.ZY(2021-2023)-0208)+2 种基金Youth Program of the National Natural Science Foundation of China(No.81903831)Shanghai Municipality:Shanghai Chenguang Program(No.19CG48)Natural Science Foundation of Shanghai(No.24ZR1465900)。
文摘Lingguizhugan Decoction(LGZG)demonstrates significant efficacy in treating various cardiovascular diseases clinically,yet its precise mechanism of action remains elusive.This study aimed to elucidate the potential mechanisms and effects of LGZG on isoproterenol(ISO)continuous stimulation-induced chronic heart failure(CHF)in mice,providing direct experimental evidence for further clinical applications.In vivo,continuous ISO infusion was administered to mice,and ventricular myocytes were utilized to explore LGZG's potential mechanism of action on theβ1-adrenergic receptor(β1-AR)/Gs/G protein-coupled receptor kinases(GRKs)/β-arrestin signaling deflection system in the heart.The findings reveal that LGZG significantly reduced the messenger ribonucleic acid(mRNA)expression of hypertrophy-related biomarkers[atrial natriuretic peptide(ANP)and B-type natriuretic peptide(BNP)]and improved cardiac remodeling and left ventricular diastolic function in mice with ISO-induced CHF.Furthermore,LGZG inhibited the overactivation of Gs/cyclic adenosine monophosphate(c AMP)/protein kinase A(PKA)signaling and downregulated the downstream transcriptional activity of c AMP-response element binding protein(CREB)and the expression of the coactivator CBP/P300.Notably,LGZG downregulated the expression ofβ-arrestin1 and GRK 2/3/5 while upregulating the expression ofβ1-AR andβ-arrestin2.These results suggest that LGZG inhibits Gs/c AMP/PKA signaling andβ-arrestin/GRK-mediated desensitization and internalization ofβ1-AR,potentially exerting cardioprotective effects through the synergistic regulation of theβ1-AR/Gs/GRKs/β-arrestin signaling deflection system via multiple pathways.
基金Supported by the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences,No.CI2021A00806High Level Chinese Medical Hospital Promotion Project,No.HLCMHPP2023086the Fundamental Research Funds for the Central Public Welfare Research Institutes,No.ZZ17-XRZ-041.
文摘Chronic atrophic gastritis(CAG)is an important stage of precancerous lesions of gastric cancer.Effective treatment and regulation of CAG are essential to prevent its progression to malignancy.Traditional Chinese medicine(TCM)has shown multi-targeted efficacy in CAG treatment,with advantages in enhancing gastric mucosal barrier defense,improving microcirculation,modulating inflammatory and immune responses,and promoting lesion healing,etc.Clinical studies and meta-analyses indicate that TCM provides significant benefits,with specific Chinese herbal compounds and monomers demonstrating protective effects on the gastric mucosa through mechanisms including anti-inflammation,antioxidation,and regulation of cellular proliferation and apoptosis,etc.Finally,it is pointed out that the efficacy of TCM in the treatment of CAG requires standardized research and unified standards,and constantly clarifies and improves the evaluation criteria of each dimension of gastric mucosal barrier function.
文摘Objective:To investigate the clinical efficacy of levofloxacin combined with ambroxol in the treatment of elderly patients with chronic obstructive pulmonary disease(COPD)and pulmonary infection.Methods:A total of 80 elderly COPD patients with pulmonary infection,treated between December 2022 and November 2023,were randomly divided into a control group and an observation group,with 40 cases in each group.The control group was treated with levofloxacin hydrochloride,while the observation group received ambroxol hydrochloride injection in addition to the treatment in the control group.Laboratory indices(white blood cell count,procalcitonin,C-reactive protein,and apolipoprotein E levels),imaging-based pulmonary lesion absorption time,hospital stay,and incidence of adverse reactions were compared between the two groups.Results:After treatment,the biochemical indices of the observation group were significantly lower than those of the control group,with highly significant differences(P<0.001).Compared to the control group,the imaging-based pulmonary lesion absorption time and hospital stay of the observation group were significantly shorter(P<0.001).Additionally,the incidence of adverse reactions in the observation group was significantly lower than in the control group(P<0.05).Conclusion:Levofloxacin combined with ambroxol demonstrates advantages in improving biochemical indices,shortening imaging-based pulmonary lesion absorption time and hospital stay,and reducing adverse reaction rates in elderly COPD patients with pulmonary infection.It holds significant clinical application value.
文摘BACKGROUND Middle meningeal artery embolization(MMAE)is emerging as a promising treatment for chronic subdural hematoma(CSDH),serving both as an adjunct to surgery and as a primary therapeutic option depending on patient presentation.Due to its low recurrence rate and minimal complications,MMAE has gained increasing acceptance among clinicians in recent years.This report presents a case of diplopia following MMAE due to the presence of a potential anastomotic artery,aiming to enhance awareness of this complication.CASE SUMMARY A 60-year-old male patient presented with a headache following head trauma,and cranial computed tomography revealed a left-sided CSDH.The patient underwent left MMAE;however,polyvinyl alcohol particles inadvertently flowed into the lacrimal artery through an anastomotic artery,resulting in diplopia due to impaired abduction of the left eye.The diplopia resolved by postoperative day 40.The patient’s headache resolved by postoperative day 7,and the hematoma completely resolved by postoperative day 108.CONCLUSION Potential anastomotic arteries in the middle meningeal artery(MMA)can lead to serious complications.Superselective angiography of the MMA or its branches prior to embolization is essential.Performing embolization distal to potential anastomotic sites can reduce risks,and the presence of an anastomosis may warrant coil embolization or termination of the procedure.
文摘BACKGROUND In diabetic patients,persistent hyperglycemia creates an optimal environment for the proliferation of pathogenic bacteria,resulting in severe complications.Con-sequently,chronic rhinosinusitis(CRS)complicated by diabetes is highly pre-valent in clinical settings.AIM To analyze the results of nasal secretion cultures in diabetic patients with CRS and identify the factors influencing postoperative recurrence.METHODS A retrospective analysis was conducted on the clinical data of 203 diabetic pa-tients with CRS with nasal polyps who underwent the Messerklinger technique at Qingdao Hiser Hospital Affiliated of Qingdao University between January 2021 and January 2023.Preoperative nasal secretions were cultured to determine the types and distribution of pathogenic bacteria and assess antimicrobial suscept-ibility.Based on a one-year follow-up,patients were categorized into recurrence and nonrecurrence groups to analyze differences in their clinical data.Univariate and multivariate analyses were used to identify factors influencing postoperative recurrence.RESULTS Pathogens were detected in 153 of the 203 nasal secretion specimens collected from diabetic patients with CRS.A total of 134 pathogenic bacteria strains were isolated and identified,including 81 strains(60.4%)of gram-positive bacteria and 53 strains(39.6%)of gram-negative bacteria.Gram-positive bacteria exhibited relatively high resistance to penicillin G and erythromycin,while remaining highly sensitive to vancomycin,gentamicin,and rifampicin.Gram-negative bacteria demonstrated relatively high resistance to cefazolin and gentamicin,but showed high sensitivity to imipenem,meropenem,cefepime,and ceftazidime.Univariate analysis revealed statistically significant differences between the recurrence and nonrecurrence groups in fasting blood glucose levels,smoking history,Lund-Mackay scores,visual analog scale(VAS)scores,nasal septum deviation,allergic rhinitis,bronchial asthma,postoperative infection,long-term use of nasal decongestants,and adherence to medical prescriptions.Multivariate regression analysis identified fasting blood glucose levels and VAS-measured nasal symptom severity scores as independent factors influencing postoperative recurrence.CONCLUSION In CRS patients with nasal polyps(CRSwNP),the detection rate of nasal pathogens is relatively high,and most of the isolated bacteria exhibit antimicrobial resistance.Additionally,the blood glucose level of patients with CRS combined with CRSwNP is a risk factor for postoperative recurrence.
基金Huxiang TCM Physique Intervention Clinical Research Center,No.2023SK4061Traditional Chinese Medicine Research Project of Hunan Province,No.B2023065+4 种基金Hunan Province"14th Five-Year Plan"key specialty of TCM,No.[2023]4Hunan University of Chinese Medicine and Hospital Joint Foundation,No.2023XYLH019 and 2024XYLH365R&D Plan for Key Areas of Hunan Provincial Department of Science and Technology,No.2019SK2321Excellent Youth Program of Hunan Education Department,No.24B0346Hunan Provincial Natural Science Foundation for Young Scientists,No.2025JJ60626.
文摘BACKGROUND Anxiety and depression are prevalent among patients with chronic heart failure(CHF)and can adversely contribute to treatment adherence and clinical outcomes.Poor fluid restriction adherence is a widespread challenge in the management of CHF.To effectively manage disease progression and alleviate symptoms,it is crucial to identify key influencing factors to facilitate the implementation of targeted interventions.AIM To investigate the status of anxiety and depression among patients with CHF and determine the factors contributing to poor fluid restriction adherence.METHODS Three hundred CHF patients seeking medical treatment at The First Hospital of Hunan University of Traditional Chinese Medicine between June 2021 and June 2023 were included in the study.Questionnaires,including the Psychosomatic Symptom Scale,Self-Rating Anxiety Scale,Self-Rating Depression Scale,and Fluid Restriction Adherence Questionnaire were administered to patients.Based on their anxiety and depression scores,patients were categorized into anxiety/depression and non-anxiety/depression groups,as well as fluid restriction adherence and fluid restriction non-adherence groups.General patient data were collected,and univariate and logistic regression analyses were conducted to determine the occurrence of depression and anxiety.Logistic regression analysis was used to identify independent factors influencing fluid restriction adherence.RESULTS Statistically significant differences in age,New York Heart Association(NYHA)grading,marital status,educational attainment,and family support were observed between depressed and non-depressed CHF patients(P<0.05).Age,NYHA grading,marital status,educational attainment,and family support were identified as factors influencing the development of depression.The anxiety and non-anxiety groups differed statistically in terms of gender,age,NYHA grading,smoking history,alcohol consumption history,monthly income,educational attainment,and family support(P<0.05).Gender,smoking,alcohol consumption,monthly income,and educational attainment affected anxiety in these patients.The fluid restriction adherence rate was 28.0%,and thirst sensation,anxiety,and depression were identified as independent influencing factors.CONCLUSION CHF patients are susceptible to anxiety and depression,with multiple associated influencing factors.Moreover,anxiety and depression are independent factors that can influence fluid restriction adherence in these patients.
