Tyrosine kinase inhibitors(TKIs)are used to treat patients with chronic myelogenous leukemia(CML),leading to a nearly normal life expectancy.Sprycel(dasatinib)-induced chylothorax has rarely been reported in patients ...Tyrosine kinase inhibitors(TKIs)are used to treat patients with chronic myelogenous leukemia(CML),leading to a nearly normal life expectancy.Sprycel(dasatinib)-induced chylothorax has rarely been reported in patients undergoing CML treatment.We report a 10-year case history of chronic chylothorax that persisted despite discontinuation of dasatinib in a patient with otherwise excellent results after switching to another TKI.Herein,we discuss a conservative treatment approach that uses symptom-based thoracentesis instead of surgical ligation of the thoracic duct.This approach may reduce patient morbidity and prevent the need for complex surgical procedures.TKIs have revolutionized CML treatment;however,these powerful medications are not without patient morbidity.展开更多
This study evaluated the impact of chronicity (onset of injury to admission in-terval) on three domains of functional outcomes for a large group of traumatic brain injured (TBI) survivors. Subjects included 528 TBI ad...This study evaluated the impact of chronicity (onset of injury to admission in-terval) on three domains of functional outcomes for a large group of traumatic brain injured (TBI) survivors. Subjects included 528 TBI adults who were treated in post-hospital residential rehabilitation centers. Subjects were assigned to one of three chronicity groups: 1) Early Interval (EI), 2.00 - 8.00 months n = 245, 2) Mid Interval (MI), 8.01 - 24.00 months n = 129, and (3) Late Interval (LI), 24.01 months and greater n = 154. Functional status was assessed with the MPAI-4. RM MANCOVA was applied to evaluate differences among groups from admission to discharge. Rasch analysis demonstrated satisfactory construct validity and internal consistency (Person reliability = 0.90 - 0.94, Item reliability = 0.99) for the admission and discharge MPAI-4s. Controlling for LOS and age, the RM MANCOVA revealed that each chronicity group showed significant improvement in MPAI-4 abilities, adjustment, and participation indices from admission to discharge (p < 0.001). Improvement observed from admission to discharge was the greatest among the EI group (p < 0.001). This study demonstrated the utility of multivariate statistical approaches for understanding the complexities of TBI treatment outcomes. As measured across three domains of functioning, rehabilitation was effective in reducing disability for participants in each chronicity group. Of the three groups, EI participants presented as the most disabled at admission but also made the greatest gains when assessed at discharge.展开更多
Knee osteoarthritis(KOA)represents one of the most common causes of chronic pain.The high prevalence and disability rates of KOA impose a severe burden on both individuals and society.In contrast to cutaneous pain,KOA...Knee osteoarthritis(KOA)represents one of the most common causes of chronic pain.The high prevalence and disability rates of KOA impose a severe burden on both individuals and society.In contrast to cutaneous pain,KOA-induced joint pain is characterized as a deep tissue pain that potentially involves distinct subgroups of peripheral sensory neurons and central processing mechanisms.Furthermore,KOA pain is closely related to locomotion activity.Impaired sensorimotor integration and pain mutually reinforce each other in KOA,forming a vicious cycle that exacerbates disease progression.In this review,we highlight the key differences between KOA pain and cutaneous pain,and the latter has been extensively studied in the pain field.We hope to offer new insights into the central mechanisms and development of new treatment strategies for KOA based on the interactions between impaired sensorimotor integration and chronic joint pain.展开更多
Chronic migraine(CM)is a prevalent and highly debilitating neurological disorder.Functional magnetic resonance imaging(fMRI)studies have demonstrated associations between abnormal brain region activation and CM,yet th...Chronic migraine(CM)is a prevalent and highly debilitating neurological disorder.Functional magnetic resonance imaging(fMRI)studies have demonstrated associations between abnormal brain region activation and CM,yet the underlying complex neural circuitry mechanisms remain unclear.The spinal trigeminal nucleus caudalis(Sp5C)serves as the primary central hub for orofacial nociceptive input,receiving trigeminal pain signals and projecting to higher-order centers such as the thalamus.Therefore,we sought to investigate whether the Sp5C region and its associated circuits were involved in CM pathogenesis.In this study,we established a CM mouse model through repeated intraperitoneal injections of nitroglycerin(NTG).Using a combination of in vivo fiber photometry and in vitro c-Fos immunohistochemistry,we found a marked periorbital and plantar mechanical allodynia in CM mice,accompanied by increased glutamatergic neuronal activity in Sp5C.Chemogenetic manipulation of Sp5C glutamatergic neurons(Sp5CV^(glut2))bidirectionally modulated migraine-like behaviors and induced pain-related affective states,as evidenced by conditioned place preference/aversion(CPP/CPA)paradigms.Anterograde viral tracing revealed dense projections from Sp5C^(Vglut2)to the subthalamic nucleus(STN),which was activated in CM mice.Optogenetic activation of the Sp5C-STN pathway similarly produced migraine-like behaviors and pain-related aversive memory in mice.Altogether,we revealed a critical role of the Sp5CVglut2-STN circuit in the development and modulation of CM.Our findings provide novel mechanistic insights into the central mechanisms underlying CM,establishing potential theoretical foundations for clinical diagnosis and therapeutic development.展开更多
Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apopt...Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apoptosis in glaucoma.Modulation of Kir4.1 expression in Müller cells may therefore be a potential strategy for attenuating retinal ganglion cell damage in glaucoma.In this study,we identified seven predicted phosphorylation sites in Kir4.1 and constructed lentiviral expression systems expressing Kir4.1 mutated at each site to prevent phosphorylation.Following this,we treated Müller glial cells in vitro and in vivo with the m Glu R I agonist DHPG to induce Kir4.1 or Kir4.1 Tyr^(9)Asp overexpression.We found that both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited activation of Müller glial cells.Subsequently,we established a rat model of chronic ocular hypertension by injecting microbeads into the anterior chamber and overexpressed Kir4.1 or Kir4.1 Tyr^(9)Asp in the eye,and observed similar results in Müller cells in vivo as those seen in vitro.Both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited Müller cell activation,regulated the balance of Bax/Bcl-2,and reduced the m RNA and protein levels of pro-inflammatory factors,including interleukin-1βand tumor necrosis factor-α.Furthermore,we investigated the regulatory effects of Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression on the release of pro-inflammatory factors in a co-culture system of Müller glial cells and microglia.In this co-culture system,we observed elevated adenosine triphosphate concentrations in activated Müller cells,increased levels of translocator protein(a marker of microglial activation),and elevated interleukin-1βm RNA and protein levels in microglia induced by activated Müller cells.These changes could be reversed by Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression in Müller cells.Kir4.1 overexpression,but not Kir4.1 Tyr^(9)Asp overexpression,reduced the number of proliferative and migratory microglia induced by activated Müller cells.Collectively,these results suggest that the tyrosine residue at position nine in Kir4.1 may serve as a functional modulation site in the retina in an experimental model of glaucoma.Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression attenuated Müller cell activation,reduced ATP/P2X receptor–mediated interactions between glial cells,inhibited microglial activation,and decreased the synthesis and release of pro-inflammatory factors,consequently ameliorating retinal ganglion cell apoptosis in glaucoma.展开更多
Cardiovascular disease(CVD)is often accompanied by chronic kidney disease(CKD)and metabolic disorders such as obesity and type 2 diabetes^([1]).The coexistence of these conditions can lead to systemic dysfunction and ...Cardiovascular disease(CVD)is often accompanied by chronic kidney disease(CKD)and metabolic disorders such as obesity and type 2 diabetes^([1]).The coexistence of these conditions can lead to systemic dysfunction and substantially increase adverse cardiovascular outcomes.To describe this interplay,the American Heart Association(AHA)recently proposed the concept of cardiovascular-kidney-metabolic(CKM)syndrome^([1]).However,its risk-enhancing factors and underlying mechanisms remain unclear.展开更多
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
Chronic pain and disability following acute orthopedic trauma are not only physical concerns but also deeply intertwined with psychological well-being.The recent retrospective cohort study by Yang et al,published,prov...Chronic pain and disability following acute orthopedic trauma are not only physical concerns but also deeply intertwined with psychological well-being.The recent retrospective cohort study by Yang et al,published,provides compelling evidence of significant associations between depression,anxiety,and postoperative recovery.These findings align with an expanding body of literature that confirms the need for orthopedic rehabilitation to adopt a biopsychosocial perspective.This letter contextualizes Yang et al’s study within current evidence,highlighting the roles of sleep disturbance,catastrophizing,stress,neurobiological mechanisms,and coping strategies in shaping recovery.It further emphasizes the importance of integrating nursing-led and multidisciplinary interventions to address both physical and psychological domains,ultimately promoting holistic recovery.展开更多
AIM:To compare the efficacy of goniosynechialysis(GSL)under a microscope alone(GM)and under direct gonioscopy(GG)for chronic angle-closure glaucoma(CACG)coexisted with cataract.METHODS:A prospective,single-center,and ...AIM:To compare the efficacy of goniosynechialysis(GSL)under a microscope alone(GM)and under direct gonioscopy(GG)for chronic angle-closure glaucoma(CACG)coexisted with cataract.METHODS:A prospective,single-center,and randomized controlled trial was conducted.Patients diagnosed as CACG and cataract were randomly allocated into either GM group or GG group.In GM group,the range of peripheral anterior synechiae(PAS)was confirmed through gonio-lens after phacoemulsification with intraocular lens implantation(PEI).PAS was separated only under a microscope.After separating the closed angle of 360°by this method,we used a surgical gonioscope to confirm the PAS range.If any remaining PAS was present,we would separate them with an iris repositor under the direct gonio-lens until angle of 360°was reopened.In GG group,PAS was separated under direct gonioscopy after PEI until angle of 360°was reopened.The range of residual PAS after GSLs was the primary outcome.Intraoperative complications(hyphema),intraocular pressure(IOP)and anti-glaucoma medication usage after operation were the secondary outcomes.RESULTS:Sixty eyes were included,each group comprising 30 eyes.The average age[GM group:66.3±6.8y(12 males),GG group:67.6±8.9y(7 males),P=0.550],the baseline IOP(GM group:29.6±11.5 mm Hg,GG group:32.4±12.2 mm Hg,P=0.366)and the average initial PAS extent(GM group:8.9±2.6h,GG group:9.4±2.5h,P=0.425)were similar in the two groups.In GM group,the PAS range reduced from 8.9±2.6h before operation to 7.2±2.9h after PEI and 3.3±2.2h after GSL.In GG group,the PAS range reduced from 9.4±2.5h before operation to 7.5±2.9h after PEI and 0.1±0.3h after GSL.The PAS after PEI was significantly reduced compared to the preoperative PAS in both groups(all P<0.001).The extent of residual PAS after GSL in GM group was larger than that in GG group with significant statistical difference(P<0.001).Patients who underwent GSL without a gonioscope were more likely to develop hyphema than those who underwent GSL under direct gonioscopy.The difference of hyphema grade between the two groups was statistically significant(P=0.019).CONCLUSION:PEI alone can not open 360°of angle completely.PEI+GSL significantly reduced PAS range.But for patients with CACG,GSL under a microscope alone is more difficult to separate stable PAS completely and adequately than GSL under direct gonioscopy.展开更多
Neuroinflammation is an inflammatory response in the central nervous system associated with various neurological conditions.The inflammatory process is typically treated with non-steroidal and steroidal anti-inflammat...Neuroinflammation is an inflammatory response in the central nervous system associated with various neurological conditions.The inflammatory process is typically treated with non-steroidal and steroidal anti-inflammatory drugs,which have a range of serious adverse effects.As an alternative,naturally derived molecules such as quercetin and its derivatives show promising anti-inflammatory properties and beneficial effects on various physiological functions.Our objective was to synthesize the evidence on the anti-inflammatory effect of quercetin and its derivatives in in vivo models,in the face of neuroinflammatory insults induced by lipopolysaccharide,through a systematic review and meta-analysis.A search of the preclinical literature was conducted across four databases(Pub Med,Web of Science,Scielo,and Google Scholar).Studies were selected based on inclusion and exclusion criteria,assessed for methodological quality using CAMARADES,and risk of bias using the SYRCLE tool,and data were extracted from the studies.The quantitative assessment of quercetin effects on the expression of pro-inflammatory cytokines and microgliosis was performed through a meta-analysis.A total of 384 potentially relevant articles were identified,of which 11 studies were included in the analysis.The methodological quality was assessed,resulting in an average score of 5.8/10,and the overall risk of bias analysis revealed a lack of methodological clarity in most studies.Furthermore,through the meta-analysis,it was observed that treatment with quercetin statistically reduces pro-inflammatory cytokines,such as tumor necrosis factor alpha,interleukin 6,interleukin 1β(n=89;SMD=–2.00;95%CI:–3.29 to–0.71),and microgliosis(n=33;SMD=–2.56;95%CI:–4.07 to–1.10).In terms of underlying mechanisms,quercetin and its derivatives exhibit antioxidant and anti-apoptotic properties,possibly through the nuclear factor erythroid 2-related factor 2(Nrf2)/HO-1 pathways,increasing the expression of antioxidant enzymes and reducing reactive species,and modulating the caspase pathway,increasing levels of anti-apoptotic proteins and decreasing proapoptotic proteins.Quercetin and its derivatives exhibit highly pleiotropic actions that simultaneously contribute to preventing neuroinflammation.However,despite promising results in animal models,future directions should focus on well-designed clinical studies to assess the safety,bioavailability,and efficacy of quercetin and its derivatives in humans.Additionally,standardization of methods and dosages in studies is crucial to ensure consistency of findings and optimize their application in clinical settings.展开更多
Mesenchymal stem cell-derived extracellular vesicles have emerged as a promising form of regenerative and immunomodulatory therapy;indeed,micro(mi)RNAs contained within mesenchymal stem cell-derived extracellular vesi...Mesenchymal stem cell-derived extracellular vesicles have emerged as a promising form of regenerative and immunomodulatory therapy;indeed,micro(mi)RNAs contained within mesenchymal stem cell-derived extracellular vesicles modulate target gene expression and impact disease-associated pathways.Chronic alcohol consumption leads to neuroinflammation,brain damage,and impaired cognition.Evidence indicates that females are more vulnerable to alcohol-induced damage than males.While mesenchymal stem cell-derived extracellular vesicles have been studied in various neuroinflammatory conditions,their potential to counteract alcohol-induced brain damage remains unclear.In this study,we investigated whether repeated intravenous administration of mesenchymal stem cell-derived extracellular vesicles could ameliorate neuroinflammation and behavioral impairment induced by chronic alcohol consumption in female mice.Mesenchymal stem cell-derived extracellular vesicles diminished the increased binding of a micro-positron emission tomography tracer(^(18)F-FDG)when analyzing whole-brain 3D images and brain coronal sections of ethanol-treated mice.Mesenchymal stem cell-derived extracellular vesicle administration protected against ethanol-induced proinflammatory gene upregulation,cognitive dysfunction,and the conditioned rewarding effects of cocaine.MiRNA sequencing data from mesenchymal stem cell-derived extracellular vesicles revealed the elevated expression of extracellular vesicle-derived miR-483-5p and miR-140-3p in the brains of ethanol-treated female mice following mesenchymal stem cell-derived extracellular vesicle administration.In addition,mesenchymal stem cell-derived extracellular vesicles modulated the expression of pro-inflammatory-related miRNA target genes(e.g.,Socs3,Tnf,Mtor,and Atf6)in the brains of ethanol-treated female mice.These results suggest that mesenchymal stem cell-derived extracellular vesicles could function as a neuroprotective therapy to ameliorate the neuroinflammation,cognitive dysfunction,and conditioned rewarding effects of cocaine associated with chronic alcohol consumption.展开更多
With the intensification of population aging in China,the problem of cognitive impairment in the elderly has become increasingly prominent,attracting widespread attention from all sectors of society.Geriatric cognitiv...With the intensification of population aging in China,the problem of cognitive impairment in the elderly has become increasingly prominent,attracting widespread attention from all sectors of society.Geriatric cognitive impairment is characterized by chronicity,which not only seriously threatens the health of the elderly and reduces their quality of life,but also imposes a heavy burden on families and society due to its long course.Attaching importance to and strengthening the chronic disease management of elderly cognitive impairment has profound significance for delaying disease progression,improving patients’quality of life,and reducing the burden of family care.Therefore,this paper first comprehensively understands elderly cognitive impairment by briefly elaborating on its definition and characteristics;on this basis,it focuses on exploring effective strategies for the chronic disease management of elderly cognitive impairment,hoping to provide new ideas and methods for the management of this condition and offer useful references for relevant clinical research and practice.展开更多
Chronic heart failure(CHF)impairs cognitive function.Xijiaqi Formula(XJQ),a traditional Chinese medicine(TCM)used clinically to treat CHF,demonstrates potential for improving cognition in CHF patients.However,its prec...Chronic heart failure(CHF)impairs cognitive function.Xijiaqi Formula(XJQ),a traditional Chinese medicine(TCM)used clinically to treat CHF,demonstrates potential for improving cognition in CHF patients.However,its precise mechanism in treating post-CHF cognitive dysfunction remains unclear.This study systematically investigates XJQ’s effects on post-CHF cognitive dysfunction and the underlying mechanisms.The components of XJQ were identified through liquid chromatography-mass spectrometry.CHF was induced in rats via ligation of the left anterior descending coronary artery,followed by six weeks of XJQ treatment.Cardiac function was evaluated through echocardiography and hemodynamic parameters,while cognitive function was assessed using Morris water maze(MWM)and open field tests(OFT).XJQ treatment enhanced both cardiac and cognitive functions in CHF rats.Network pharmacology identified 12 core active components of XJQ and indicated its effect on cognitive dysfunction involved regulating synapses,inflammation,and phosphodiesterase 4(PDE4)-dependent cyclic adenosine monophosphate(cAMP)signaling.XJQ inhibited microglial and astrocyte activation,decreased proinflammatory cytokines,and mitigated neuronal damage.Notably,XJQ promoted synaptic repair and dendritic growth by downregulating PDE4 and upregulating cAMP,protein kinase A(PKA),cAMP-response element binding protein(CREB),brain-derived neurotrophic factor(BDNF),PSD95,and synapsin I levels.Molecular docking and Bio-layer interferometry assays confirmed direct binding of quercetin,kaempferol,isorhamnetin,and darutoside to PDE4.In conclusion,XJQ alleviates neuroinflammation and enhances synaptic plasticity to improve cognitive dysfunction in CHF rats via the PDE4/cAMP/PKA/CREB signaling pathway.These findings provide valuable insight into the heart-brain axis.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
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 investigate the clinical efficacy of electrophysiological therapy under different parameter modes in chronic pelvic pain syndrome(CPPS).Methods:A total of 95patients with CPPS from the Department of Urolo...Objective:To investigate the clinical efficacy of electrophysiological therapy under different parameter modes in chronic pelvic pain syndrome(CPPS).Methods:A total of 95patients with CPPS from the Department of Urology,First Affiliated Hospital of Jinan University,were selected and treated with electrophysiological therapy.They were randomly divided into three groups:the fixed-parameter AA7 treatment group,the P2+P4 treatment group,and the precision treatment group(individualized parameter treatment).Pain scores of patients in each group were compared before and after treatment,with a pain score of 0 indicating cure.The cure rate of each group was observed.Results:The average ages of the AA7 group,P2+P4 group,and precision treatment group were 34±14.17 years,35.58±12.57 years,and 35.5±11.27 years,respectively.There was no significant difference in age among the three groups(p>0.05).Before treatment,the pain scores of the AA7 group,P2+P4 group,and precision treatment group were 4.14±1.74,4.64±1.72,and 3.50±1.89,respectively,with no significant differences among the groups(p>0.05).After treatment,the pain scores were 0.71±0.99 for the AA7 group(cure rate:57%),0.49±0.79 for the P2+P4 group(cure rate:67%),and 0.50±0.77 for the precision treatment group(cure rate:64%),with no significant differences among the groups(p>0.05).The cure rates for different pain locations were as follows:83%for lower abdominal pain,74%for perineal pain,62%for dysuria,49%for testicular pain,and 75%for inguinal pain.Conclusion:The pathogenesis of CPPS is complex and diverse,with numerous treatment options and uncertain efficacy,posing significant challenges to clinical practice.This study showed that electrophysiological therapy under different parameter modes significantly reduced pain scores before and after treatment,indicating significant therapeutic effects on CPPS.All three modes demonstrated good cure rates.Individualized precision treatment and fixed-mode P2+P4 or AA7 treatment were safe and effective in CPPS treatment and are worth promoting.Fixed-mode P2+P4 and AA7,due to their easier standardization of parameters and patch modes,reduced the learning curve and had better potential for widespread application.展开更多
Chronic cerebral hypoperfusion can lead to neuronal necrosis,trigger inflammatory responses,promote white matter damage,and ultimately result in cognitive impairment.Consequently,chronic cerebral hypoperfusion is an i...Chronic cerebral hypoperfusion can lead to neuronal necrosis,trigger inflammatory responses,promote white matter damage,and ultimately result in cognitive impairment.Consequently,chronic cerebral hypoperfusion is an important factor influencing the onset and progression of vascular dementia.The myelin sheath is a critical component of white matter,and damage and repair of the white matter are closely linked to myelin sheath integrity.This article reviews the role of microglia in vascular dementia,focusing on their effects on myelin sheaths and the potential therapeutic implications.The findings suggest that ischemia and hypoxia cause disruption of the blood-brain barrier and activate microglia,which may worsen blood-brain barrier damage through the release of matrix-degrading enzymes.Microglia-mediated metabolic reprogramming is recognized as an important driver of inflammation.Damage to the blood-brain barrier and subsequent inflammation can lead to myelin injury and accelerate the progression of vascular dementia.Early activation of microglia is a protective response that contributes to the maintenance of blood-brain barrier integrity through sensing,debris-clearing,and defensive mechanisms.However,prolonged activation can trigger a shift in microglia toward the pro-inflammatory M1 phenotype,resulting in myelin damage and cognitive impairment.Triggering receptor expressed on myeloid cells 2 and triggering receptor expressed on myeloid cells 1 have been identified as potential biomarkers for vascular dementia,as both are closely linked to cognitive decline.Although effective clinical treatments for myelin damage in the central nervous system are currently lacking,researchers are actively working to develop targeted therapies.Several drugs,including nimodipine,dopaminergic agents,simvastatin,biotin,and quetiapine,have been evaluated for clinical use in treating microglial and myelin damage.Future research will face challenges in developing targeted therapeutic strategies for vascular dementia,requiring further investigation into the timing,duration,and specific mechanisms of microglial activation,as well as the exploration of new drug combinations and additional therapeutic targets.展开更多
Objective:To investigate the quantitative assessment efficacy of chest CT combined with serum Vanin-1 and SPP1 in determining the progression stage of chronic obstructive pulmonary disease(COPD).Methods:A total of 100...Objective:To investigate the quantitative assessment efficacy of chest CT combined with serum Vanin-1 and SPP1 in determining the progression stage of chronic obstructive pulmonary disease(COPD).Methods:A total of 100 COPD subjects from our hospital from January 2020 to December 2023 were included and randomly divided into a healthy control group and an experimental group(50 cases each).The healthy control group underwent slow vital capacity measurement using a spirometer,while the experimental group underwent high-resolution thin-slice CT scans and serum Vanin-1 and SPP1 concentration measurements.Pulmonary function parameters,symptom burden,biomarker concentrations,and imaging characteristics were compared between the two groups.Results:The FEV1/FVC ratio in the experimental group(58.3±7.2)was lower than that in the healthy control group(92.1±4.8);the total CAT score(22.4±3.5)was higher than that in the healthy control group(3.1±1.2);both Vanin-1(18.7±2.3μg/L)and SPP1(25.6±4.1μg/L)levels were higher than those in the healthy control group;LAA%-950(38.7±6.2%)and WA%(68.5±5.3%)were significantly higher than those in the healthy control group(all p<0.001).Conclusion:Chest CT combined with serum Vanin-1 and SPP1 can accurately quantify the pathological progression of COPD,providing a dual basis for clinical staging and individualized intervention.展开更多
[Objectives]To investigate the clinical efficacy of core stability training combined with conventional rehabilitation in the functional recovery of patients suffering from chronic low back pain.[Methods]A randomized c...[Objectives]To investigate the clinical efficacy of core stability training combined with conventional rehabilitation in the functional recovery of patients suffering from chronic low back pain.[Methods]A randomized controlled trial design was employed in this study.Ninety patients with chronic low back pain were recruited and randomly assigned to either a control group(n=45),which received conventional rehabilitation,or an experimental group(n=45),which received conventional rehabilitation combined with core stability training.Both groups underwent treatment for 6 weeks.Assessments were conducted using the visual analogue scale(VAS),Oswestry disability index(ODI),and finger-to-floor test prior to treatment,6 weeks following treatment,and during the follow-up period,respectively.[Results]Prior to treatment,no statistically significant differences were observed between the two patient groups in terms of general information and various baseline measurements(P>0.05).Following 6 weeks of treatment and throughout the follow-up period,both groups demonstrated significant improvements in VAS scores,ODI scores,and lumbar anteflexion range of motion compared to baseline measurements(P<0.05).Notably,the magnitude of improvement in the experimental group exceeded that of the control group,with this inter-group difference reaching statistical significance(P<0.05).No serious adverse reactions were reported during the treatment process.[Conclusions]Core stability training combined with conventional rehabilitation can significantly enhance the alleviation of pain and functional impairments in patients suffering from chronic low back pain.This approach holds valuable implications for the optimization of rehabilitation treatment protocols.展开更多
文摘Tyrosine kinase inhibitors(TKIs)are used to treat patients with chronic myelogenous leukemia(CML),leading to a nearly normal life expectancy.Sprycel(dasatinib)-induced chylothorax has rarely been reported in patients undergoing CML treatment.We report a 10-year case history of chronic chylothorax that persisted despite discontinuation of dasatinib in a patient with otherwise excellent results after switching to another TKI.Herein,we discuss a conservative treatment approach that uses symptom-based thoracentesis instead of surgical ligation of the thoracic duct.This approach may reduce patient morbidity and prevent the need for complex surgical procedures.TKIs have revolutionized CML treatment;however,these powerful medications are not without patient morbidity.
文摘This study evaluated the impact of chronicity (onset of injury to admission in-terval) on three domains of functional outcomes for a large group of traumatic brain injured (TBI) survivors. Subjects included 528 TBI adults who were treated in post-hospital residential rehabilitation centers. Subjects were assigned to one of three chronicity groups: 1) Early Interval (EI), 2.00 - 8.00 months n = 245, 2) Mid Interval (MI), 8.01 - 24.00 months n = 129, and (3) Late Interval (LI), 24.01 months and greater n = 154. Functional status was assessed with the MPAI-4. RM MANCOVA was applied to evaluate differences among groups from admission to discharge. Rasch analysis demonstrated satisfactory construct validity and internal consistency (Person reliability = 0.90 - 0.94, Item reliability = 0.99) for the admission and discharge MPAI-4s. Controlling for LOS and age, the RM MANCOVA revealed that each chronicity group showed significant improvement in MPAI-4 abilities, adjustment, and participation indices from admission to discharge (p < 0.001). Improvement observed from admission to discharge was the greatest among the EI group (p < 0.001). This study demonstrated the utility of multivariate statistical approaches for understanding the complexities of TBI treatment outcomes. As measured across three domains of functioning, rehabilitation was effective in reducing disability for participants in each chronicity group. Of the three groups, EI participants presented as the most disabled at admission but also made the greatest gains when assessed at discharge.
基金supported by the Natural Science Foundation of Beijing Municipality(No.F252065)the National Natural Science Foundation of China(No.32271190,32571323)the STI 2030 Major Project(No.2021ZD0203202)。
文摘Knee osteoarthritis(KOA)represents one of the most common causes of chronic pain.The high prevalence and disability rates of KOA impose a severe burden on both individuals and society.In contrast to cutaneous pain,KOA-induced joint pain is characterized as a deep tissue pain that potentially involves distinct subgroups of peripheral sensory neurons and central processing mechanisms.Furthermore,KOA pain is closely related to locomotion activity.Impaired sensorimotor integration and pain mutually reinforce each other in KOA,forming a vicious cycle that exacerbates disease progression.In this review,we highlight the key differences between KOA pain and cutaneous pain,and the latter has been extensively studied in the pain field.We hope to offer new insights into the central mechanisms and development of new treatment strategies for KOA based on the interactions between impaired sensorimotor integration and chronic joint pain.
基金supported by the National Natural Science Foundation of China(No.32571336 and 32271048)Research Funds of Centre for Leading Medicine and Advanced Technologies of IHM(No.2025IHM01100)。
文摘Chronic migraine(CM)is a prevalent and highly debilitating neurological disorder.Functional magnetic resonance imaging(fMRI)studies have demonstrated associations between abnormal brain region activation and CM,yet the underlying complex neural circuitry mechanisms remain unclear.The spinal trigeminal nucleus caudalis(Sp5C)serves as the primary central hub for orofacial nociceptive input,receiving trigeminal pain signals and projecting to higher-order centers such as the thalamus.Therefore,we sought to investigate whether the Sp5C region and its associated circuits were involved in CM pathogenesis.In this study,we established a CM mouse model through repeated intraperitoneal injections of nitroglycerin(NTG).Using a combination of in vivo fiber photometry and in vitro c-Fos immunohistochemistry,we found a marked periorbital and plantar mechanical allodynia in CM mice,accompanied by increased glutamatergic neuronal activity in Sp5C.Chemogenetic manipulation of Sp5C glutamatergic neurons(Sp5CV^(glut2))bidirectionally modulated migraine-like behaviors and induced pain-related affective states,as evidenced by conditioned place preference/aversion(CPP/CPA)paradigms.Anterograde viral tracing revealed dense projections from Sp5C^(Vglut2)to the subthalamic nucleus(STN),which was activated in CM mice.Optogenetic activation of the Sp5C-STN pathway similarly produced migraine-like behaviors and pain-related aversive memory in mice.Altogether,we revealed a critical role of the Sp5CVglut2-STN circuit in the development and modulation of CM.Our findings provide novel mechanistic insights into the central mechanisms underlying CM,establishing potential theoretical foundations for clinical diagnosis and therapeutic development.
基金supported by the National Natural Science Foundation of China,Nos.32271043(to ZW)and 82171047(to YM)the both Science and Technology Major Project of Shanghai,No.2018SHZDZX01 and ZJLabShanghai Center for Brain Science and Brain-Inspired Technology(to ZW)。
文摘Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apoptosis in glaucoma.Modulation of Kir4.1 expression in Müller cells may therefore be a potential strategy for attenuating retinal ganglion cell damage in glaucoma.In this study,we identified seven predicted phosphorylation sites in Kir4.1 and constructed lentiviral expression systems expressing Kir4.1 mutated at each site to prevent phosphorylation.Following this,we treated Müller glial cells in vitro and in vivo with the m Glu R I agonist DHPG to induce Kir4.1 or Kir4.1 Tyr^(9)Asp overexpression.We found that both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited activation of Müller glial cells.Subsequently,we established a rat model of chronic ocular hypertension by injecting microbeads into the anterior chamber and overexpressed Kir4.1 or Kir4.1 Tyr^(9)Asp in the eye,and observed similar results in Müller cells in vivo as those seen in vitro.Both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited Müller cell activation,regulated the balance of Bax/Bcl-2,and reduced the m RNA and protein levels of pro-inflammatory factors,including interleukin-1βand tumor necrosis factor-α.Furthermore,we investigated the regulatory effects of Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression on the release of pro-inflammatory factors in a co-culture system of Müller glial cells and microglia.In this co-culture system,we observed elevated adenosine triphosphate concentrations in activated Müller cells,increased levels of translocator protein(a marker of microglial activation),and elevated interleukin-1βm RNA and protein levels in microglia induced by activated Müller cells.These changes could be reversed by Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression in Müller cells.Kir4.1 overexpression,but not Kir4.1 Tyr^(9)Asp overexpression,reduced the number of proliferative and migratory microglia induced by activated Müller cells.Collectively,these results suggest that the tyrosine residue at position nine in Kir4.1 may serve as a functional modulation site in the retina in an experimental model of glaucoma.Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression attenuated Müller cell activation,reduced ATP/P2X receptor–mediated interactions between glial cells,inhibited microglial activation,and decreased the synthesis and release of pro-inflammatory factors,consequently ameliorating retinal ganglion cell apoptosis in glaucoma.
基金supported by the Natural Science Foundation of Beijing Municipality(Grant No.7234401)the Postdoctoral Research Foundation of China(Grant No.88014Y0226)。
文摘Cardiovascular disease(CVD)is often accompanied by chronic kidney disease(CKD)and metabolic disorders such as obesity and type 2 diabetes^([1]).The coexistence of these conditions can lead to systemic dysfunction and substantially increase adverse cardiovascular outcomes.To describe this interplay,the American Heart Association(AHA)recently proposed the concept of cardiovascular-kidney-metabolic(CKM)syndrome^([1]).However,its risk-enhancing factors and underlying mechanisms remain unclear.
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.
文摘Chronic pain and disability following acute orthopedic trauma are not only physical concerns but also deeply intertwined with psychological well-being.The recent retrospective cohort study by Yang et al,published,provides compelling evidence of significant associations between depression,anxiety,and postoperative recovery.These findings align with an expanding body of literature that confirms the need for orthopedic rehabilitation to adopt a biopsychosocial perspective.This letter contextualizes Yang et al’s study within current evidence,highlighting the roles of sleep disturbance,catastrophizing,stress,neurobiological mechanisms,and coping strategies in shaping recovery.It further emphasizes the importance of integrating nursing-led and multidisciplinary interventions to address both physical and psychological domains,ultimately promoting holistic recovery.
基金Supported by the Program for Zhejiang Leading Talent of S&T Innovation(No.2021R52012)Key Research and Development Projects of Zhejiang Province(No.2022C03112).
文摘AIM:To compare the efficacy of goniosynechialysis(GSL)under a microscope alone(GM)and under direct gonioscopy(GG)for chronic angle-closure glaucoma(CACG)coexisted with cataract.METHODS:A prospective,single-center,and randomized controlled trial was conducted.Patients diagnosed as CACG and cataract were randomly allocated into either GM group or GG group.In GM group,the range of peripheral anterior synechiae(PAS)was confirmed through gonio-lens after phacoemulsification with intraocular lens implantation(PEI).PAS was separated only under a microscope.After separating the closed angle of 360°by this method,we used a surgical gonioscope to confirm the PAS range.If any remaining PAS was present,we would separate them with an iris repositor under the direct gonio-lens until angle of 360°was reopened.In GG group,PAS was separated under direct gonioscopy after PEI until angle of 360°was reopened.The range of residual PAS after GSLs was the primary outcome.Intraoperative complications(hyphema),intraocular pressure(IOP)and anti-glaucoma medication usage after operation were the secondary outcomes.RESULTS:Sixty eyes were included,each group comprising 30 eyes.The average age[GM group:66.3±6.8y(12 males),GG group:67.6±8.9y(7 males),P=0.550],the baseline IOP(GM group:29.6±11.5 mm Hg,GG group:32.4±12.2 mm Hg,P=0.366)and the average initial PAS extent(GM group:8.9±2.6h,GG group:9.4±2.5h,P=0.425)were similar in the two groups.In GM group,the PAS range reduced from 8.9±2.6h before operation to 7.2±2.9h after PEI and 3.3±2.2h after GSL.In GG group,the PAS range reduced from 9.4±2.5h before operation to 7.5±2.9h after PEI and 0.1±0.3h after GSL.The PAS after PEI was significantly reduced compared to the preoperative PAS in both groups(all P<0.001).The extent of residual PAS after GSL in GM group was larger than that in GG group with significant statistical difference(P<0.001).Patients who underwent GSL without a gonioscope were more likely to develop hyphema than those who underwent GSL under direct gonioscopy.The difference of hyphema grade between the two groups was statistically significant(P=0.019).CONCLUSION:PEI alone can not open 360°of angle completely.PEI+GSL significantly reduced PAS range.But for patients with CACG,GSL under a microscope alone is more difficult to separate stable PAS completely and adequately than GSL under direct gonioscopy.
基金supported by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-Brasil(CAPES)[Finance Code 001](to MGS)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico(CNPq)fellowship[research grants 309840/2022-8]。
文摘Neuroinflammation is an inflammatory response in the central nervous system associated with various neurological conditions.The inflammatory process is typically treated with non-steroidal and steroidal anti-inflammatory drugs,which have a range of serious adverse effects.As an alternative,naturally derived molecules such as quercetin and its derivatives show promising anti-inflammatory properties and beneficial effects on various physiological functions.Our objective was to synthesize the evidence on the anti-inflammatory effect of quercetin and its derivatives in in vivo models,in the face of neuroinflammatory insults induced by lipopolysaccharide,through a systematic review and meta-analysis.A search of the preclinical literature was conducted across four databases(Pub Med,Web of Science,Scielo,and Google Scholar).Studies were selected based on inclusion and exclusion criteria,assessed for methodological quality using CAMARADES,and risk of bias using the SYRCLE tool,and data were extracted from the studies.The quantitative assessment of quercetin effects on the expression of pro-inflammatory cytokines and microgliosis was performed through a meta-analysis.A total of 384 potentially relevant articles were identified,of which 11 studies were included in the analysis.The methodological quality was assessed,resulting in an average score of 5.8/10,and the overall risk of bias analysis revealed a lack of methodological clarity in most studies.Furthermore,through the meta-analysis,it was observed that treatment with quercetin statistically reduces pro-inflammatory cytokines,such as tumor necrosis factor alpha,interleukin 6,interleukin 1β(n=89;SMD=–2.00;95%CI:–3.29 to–0.71),and microgliosis(n=33;SMD=–2.56;95%CI:–4.07 to–1.10).In terms of underlying mechanisms,quercetin and its derivatives exhibit antioxidant and anti-apoptotic properties,possibly through the nuclear factor erythroid 2-related factor 2(Nrf2)/HO-1 pathways,increasing the expression of antioxidant enzymes and reducing reactive species,and modulating the caspase pathway,increasing levels of anti-apoptotic proteins and decreasing proapoptotic proteins.Quercetin and its derivatives exhibit highly pleiotropic actions that simultaneously contribute to preventing neuroinflammation.However,despite promising results in animal models,future directions should focus on well-designed clinical studies to assess the safety,bioavailability,and efficacy of quercetin and its derivatives in humans.Additionally,standardization of methods and dosages in studies is crucial to ensure consistency of findings and optimize their application in clinical settings.
基金supported by the Spanish Ministry of Health‐Plan Nacional sobre Drogas(2023‐I024)the the Ministry of Science,Innovation and Universities/State ResearchAgency/10.13039/501100011033(PID2023-146865OB-I00)+2 种基金Generalitat Valenciana(CIAICO/2021/203)the Primary Addiction Care Research Network(RD21/0009/0005)FEDER Funds,GVA.
文摘Mesenchymal stem cell-derived extracellular vesicles have emerged as a promising form of regenerative and immunomodulatory therapy;indeed,micro(mi)RNAs contained within mesenchymal stem cell-derived extracellular vesicles modulate target gene expression and impact disease-associated pathways.Chronic alcohol consumption leads to neuroinflammation,brain damage,and impaired cognition.Evidence indicates that females are more vulnerable to alcohol-induced damage than males.While mesenchymal stem cell-derived extracellular vesicles have been studied in various neuroinflammatory conditions,their potential to counteract alcohol-induced brain damage remains unclear.In this study,we investigated whether repeated intravenous administration of mesenchymal stem cell-derived extracellular vesicles could ameliorate neuroinflammation and behavioral impairment induced by chronic alcohol consumption in female mice.Mesenchymal stem cell-derived extracellular vesicles diminished the increased binding of a micro-positron emission tomography tracer(^(18)F-FDG)when analyzing whole-brain 3D images and brain coronal sections of ethanol-treated mice.Mesenchymal stem cell-derived extracellular vesicle administration protected against ethanol-induced proinflammatory gene upregulation,cognitive dysfunction,and the conditioned rewarding effects of cocaine.MiRNA sequencing data from mesenchymal stem cell-derived extracellular vesicles revealed the elevated expression of extracellular vesicle-derived miR-483-5p and miR-140-3p in the brains of ethanol-treated female mice following mesenchymal stem cell-derived extracellular vesicle administration.In addition,mesenchymal stem cell-derived extracellular vesicles modulated the expression of pro-inflammatory-related miRNA target genes(e.g.,Socs3,Tnf,Mtor,and Atf6)in the brains of ethanol-treated female mice.These results suggest that mesenchymal stem cell-derived extracellular vesicles could function as a neuroprotective therapy to ameliorate the neuroinflammation,cognitive dysfunction,and conditioned rewarding effects of cocaine associated with chronic alcohol consumption.
文摘With the intensification of population aging in China,the problem of cognitive impairment in the elderly has become increasingly prominent,attracting widespread attention from all sectors of society.Geriatric cognitive impairment is characterized by chronicity,which not only seriously threatens the health of the elderly and reduces their quality of life,but also imposes a heavy burden on families and society due to its long course.Attaching importance to and strengthening the chronic disease management of elderly cognitive impairment has profound significance for delaying disease progression,improving patients’quality of life,and reducing the burden of family care.Therefore,this paper first comprehensively understands elderly cognitive impairment by briefly elaborating on its definition and characteristics;on this basis,it focuses on exploring effective strategies for the chronic disease management of elderly cognitive impairment,hoping to provide new ideas and methods for the management of this condition and offer useful references for relevant clinical research and practice.
基金supported by the National Natural Science Foundation of China(Nos.82430116 and 82574622)the Special Fund of Central Committee High Level Chinese Medicine Hospital(Nos.DZMG-LJRC-0014,DZMG-ZJXY-23013)+1 种基金Chinese Medicine Inheritance and Innovation“Thousand Million”Talents Project(Qihuang Project 2021)Qihuang Scholarsthe Medical and Health Industry Development Project of Tongzhou District(2023).
文摘Chronic heart failure(CHF)impairs cognitive function.Xijiaqi Formula(XJQ),a traditional Chinese medicine(TCM)used clinically to treat CHF,demonstrates potential for improving cognition in CHF patients.However,its precise mechanism in treating post-CHF cognitive dysfunction remains unclear.This study systematically investigates XJQ’s effects on post-CHF cognitive dysfunction and the underlying mechanisms.The components of XJQ were identified through liquid chromatography-mass spectrometry.CHF was induced in rats via ligation of the left anterior descending coronary artery,followed by six weeks of XJQ treatment.Cardiac function was evaluated through echocardiography and hemodynamic parameters,while cognitive function was assessed using Morris water maze(MWM)and open field tests(OFT).XJQ treatment enhanced both cardiac and cognitive functions in CHF rats.Network pharmacology identified 12 core active components of XJQ and indicated its effect on cognitive dysfunction involved regulating synapses,inflammation,and phosphodiesterase 4(PDE4)-dependent cyclic adenosine monophosphate(cAMP)signaling.XJQ inhibited microglial and astrocyte activation,decreased proinflammatory cytokines,and mitigated neuronal damage.Notably,XJQ promoted synaptic repair and dendritic growth by downregulating PDE4 and upregulating cAMP,protein kinase A(PKA),cAMP-response element binding protein(CREB),brain-derived neurotrophic factor(BDNF),PSD95,and synapsin I levels.Molecular docking and Bio-layer interferometry assays confirmed direct binding of quercetin,kaempferol,isorhamnetin,and darutoside to PDE4.In conclusion,XJQ alleviates neuroinflammation and enhances synaptic plasticity to improve cognitive dysfunction in CHF rats via the PDE4/cAMP/PKA/CREB signaling pathway.These findings provide valuable insight into the heart-brain axis.
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 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 investigate the clinical efficacy of electrophysiological therapy under different parameter modes in chronic pelvic pain syndrome(CPPS).Methods:A total of 95patients with CPPS from the Department of Urology,First Affiliated Hospital of Jinan University,were selected and treated with electrophysiological therapy.They were randomly divided into three groups:the fixed-parameter AA7 treatment group,the P2+P4 treatment group,and the precision treatment group(individualized parameter treatment).Pain scores of patients in each group were compared before and after treatment,with a pain score of 0 indicating cure.The cure rate of each group was observed.Results:The average ages of the AA7 group,P2+P4 group,and precision treatment group were 34±14.17 years,35.58±12.57 years,and 35.5±11.27 years,respectively.There was no significant difference in age among the three groups(p>0.05).Before treatment,the pain scores of the AA7 group,P2+P4 group,and precision treatment group were 4.14±1.74,4.64±1.72,and 3.50±1.89,respectively,with no significant differences among the groups(p>0.05).After treatment,the pain scores were 0.71±0.99 for the AA7 group(cure rate:57%),0.49±0.79 for the P2+P4 group(cure rate:67%),and 0.50±0.77 for the precision treatment group(cure rate:64%),with no significant differences among the groups(p>0.05).The cure rates for different pain locations were as follows:83%for lower abdominal pain,74%for perineal pain,62%for dysuria,49%for testicular pain,and 75%for inguinal pain.Conclusion:The pathogenesis of CPPS is complex and diverse,with numerous treatment options and uncertain efficacy,posing significant challenges to clinical practice.This study showed that electrophysiological therapy under different parameter modes significantly reduced pain scores before and after treatment,indicating significant therapeutic effects on CPPS.All three modes demonstrated good cure rates.Individualized precision treatment and fixed-mode P2+P4 or AA7 treatment were safe and effective in CPPS treatment and are worth promoting.Fixed-mode P2+P4 and AA7,due to their easier standardization of parameters and patch modes,reduced the learning curve and had better potential for widespread application.
基金supported by the Natural Science Foundation of Beijing,No.7232279(to XW)the National Natural Science Foundation of China,No.U21A20400(to QW)Key Project of Beijing University of Chinese Medicine,Nos.2022-JYB-JBZR-004(to XW),2024-JYB-JBZD-043(to CL).
文摘Chronic cerebral hypoperfusion can lead to neuronal necrosis,trigger inflammatory responses,promote white matter damage,and ultimately result in cognitive impairment.Consequently,chronic cerebral hypoperfusion is an important factor influencing the onset and progression of vascular dementia.The myelin sheath is a critical component of white matter,and damage and repair of the white matter are closely linked to myelin sheath integrity.This article reviews the role of microglia in vascular dementia,focusing on their effects on myelin sheaths and the potential therapeutic implications.The findings suggest that ischemia and hypoxia cause disruption of the blood-brain barrier and activate microglia,which may worsen blood-brain barrier damage through the release of matrix-degrading enzymes.Microglia-mediated metabolic reprogramming is recognized as an important driver of inflammation.Damage to the blood-brain barrier and subsequent inflammation can lead to myelin injury and accelerate the progression of vascular dementia.Early activation of microglia is a protective response that contributes to the maintenance of blood-brain barrier integrity through sensing,debris-clearing,and defensive mechanisms.However,prolonged activation can trigger a shift in microglia toward the pro-inflammatory M1 phenotype,resulting in myelin damage and cognitive impairment.Triggering receptor expressed on myeloid cells 2 and triggering receptor expressed on myeloid cells 1 have been identified as potential biomarkers for vascular dementia,as both are closely linked to cognitive decline.Although effective clinical treatments for myelin damage in the central nervous system are currently lacking,researchers are actively working to develop targeted therapies.Several drugs,including nimodipine,dopaminergic agents,simvastatin,biotin,and quetiapine,have been evaluated for clinical use in treating microglial and myelin damage.Future research will face challenges in developing targeted therapeutic strategies for vascular dementia,requiring further investigation into the timing,duration,and specific mechanisms of microglial activation,as well as the exploration of new drug combinations and additional therapeutic targets.
基金Baoding Science and Technology Plan Project(Project No.:2341ZF214)。
文摘Objective:To investigate the quantitative assessment efficacy of chest CT combined with serum Vanin-1 and SPP1 in determining the progression stage of chronic obstructive pulmonary disease(COPD).Methods:A total of 100 COPD subjects from our hospital from January 2020 to December 2023 were included and randomly divided into a healthy control group and an experimental group(50 cases each).The healthy control group underwent slow vital capacity measurement using a spirometer,while the experimental group underwent high-resolution thin-slice CT scans and serum Vanin-1 and SPP1 concentration measurements.Pulmonary function parameters,symptom burden,biomarker concentrations,and imaging characteristics were compared between the two groups.Results:The FEV1/FVC ratio in the experimental group(58.3±7.2)was lower than that in the healthy control group(92.1±4.8);the total CAT score(22.4±3.5)was higher than that in the healthy control group(3.1±1.2);both Vanin-1(18.7±2.3μg/L)and SPP1(25.6±4.1μg/L)levels were higher than those in the healthy control group;LAA%-950(38.7±6.2%)and WA%(68.5±5.3%)were significantly higher than those in the healthy control group(all p<0.001).Conclusion:Chest CT combined with serum Vanin-1 and SPP1 can accurately quantify the pathological progression of COPD,providing a dual basis for clinical staging and individualized intervention.
文摘[Objectives]To investigate the clinical efficacy of core stability training combined with conventional rehabilitation in the functional recovery of patients suffering from chronic low back pain.[Methods]A randomized controlled trial design was employed in this study.Ninety patients with chronic low back pain were recruited and randomly assigned to either a control group(n=45),which received conventional rehabilitation,or an experimental group(n=45),which received conventional rehabilitation combined with core stability training.Both groups underwent treatment for 6 weeks.Assessments were conducted using the visual analogue scale(VAS),Oswestry disability index(ODI),and finger-to-floor test prior to treatment,6 weeks following treatment,and during the follow-up period,respectively.[Results]Prior to treatment,no statistically significant differences were observed between the two patient groups in terms of general information and various baseline measurements(P>0.05).Following 6 weeks of treatment and throughout the follow-up period,both groups demonstrated significant improvements in VAS scores,ODI scores,and lumbar anteflexion range of motion compared to baseline measurements(P<0.05).Notably,the magnitude of improvement in the experimental group exceeded that of the control group,with this inter-group difference reaching statistical significance(P<0.05).No serious adverse reactions were reported during the treatment process.[Conclusions]Core stability training combined with conventional rehabilitation can significantly enhance the alleviation of pain and functional impairments in patients suffering from chronic low back pain.This approach holds valuable implications for the optimization of rehabilitation treatment protocols.
