Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life ...Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.展开更多
BACKGROUND Colorectal cancer(CRC)is one of the most prevalent and lethal malignant tumors worldwide.Currently,surgical intervention was the primary treatment modality for CRC.However,increasing studies have revealed t...BACKGROUND Colorectal cancer(CRC)is one of the most prevalent and lethal malignant tumors worldwide.Currently,surgical intervention was the primary treatment modality for CRC.However,increasing studies have revealed that CRC patients may experience postoperative cognitive dysfunction(POCD).AIM To establish a risk prediction model for POCD in CRC patients and investigate the preventive value of dexmedetomidine(DEX).METHODS A retrospective analysis was conducted on clinical data from 140 CRC patients who underwent surgery at the People’s Hospital of Qian Nan from February 2020 to May 2024.Patients were allocated into a modeling group(n=98)and a validation group(n=42)in a 7:3 ratio.General clinical data were collected.Additionally,in the modeling group,patients who received DEX preoperatively were incorporated into the observation group(n=54),while those who did not were placed in the control group(n=44).The incidence of POCD was recorded for both cohorts.Data analysis was performed using statistical product and service solutions 20.0,with t-tests orχ^(2) tests employed for group comparisons based on the data type.Least absolute shrinkage and selection operator regression was applied to identify influencing factors and reduce the impact of multicollinear predictors among variables.Multivariate analysis was carried out using Logistic regression.Based on the identified risk factors,a risk prediction model for POCD in CRC patients was developed,and the predictive value of these risk factors was evaluated.RESULTS Significant differences were observed between the cognitive dysfunction group and the non-cognitive dysfunction group in diabetes status,alcohol consumption,years of education,anesthesia duration,intraoperative blood loss,intraoperative hypoxemia,use of DEX during surgery,intraoperative use of vasoactive drugs,surgical time,systemic inflammatory response syndrome(SIRS)score(P<0.05).Multivariate Logistic regression analysis identified that diabetes[odds ratio(OR)=4.679,95%confidence interval(CI)=1.382-15.833],alcohol consumption(OR=5.058,95%CI:1.255-20.380),intraoperative hypoxemia(OR=4.697,95%CI:1.380-15.991),no use of DEX during surgery(OR=3.931,95%CI:1.383-11.175),surgery duration≥90 minutes(OR=4.894,95%CI:1.377-17.394),and a SIRS score≥3(OR=4.133,95%CI:1.323-12.907)were independent risk factors for POCD in CRC patients(P<0.05).A risk prediction model for POCD was constructed using diabetes,alcohol consumption,intraoperative hypoxemia,non-use of DEX during surgery,surgery duration,and SIRS score as factors.A receiver operator characteristic curve analysis of these factors revealed the model’s predictive sensitivity(88.56%),specificity(70.64%),and area under the curve(AUC)(AUC=0.852,95%CI:0.773-0.919).The model was validated using 42 CRC patients who met the inclusion criteria,demonstrating sensitivity(80.77%),specificity(81.25%),and accuracy(80.95%),and AUC(0.805)in diagnosing cognitive impairment,with a 95%CI:0.635-0.896.CONCLUSION Logistic regression analysis identified that diabetes,alcohol consumption,intraoperative hypoxemia,non-use of DEX during surgery,surgery duration,and SIRS score vigorously influenced the occurrence of POCD.The risk prediction model based on these factors demonstrated good predictive performance for POCD in CRC individuals.This study offers valuable insights for clinical practice and contributes to the prevention and management of POCD under CRC circumstances.展开更多
BACKGROUND To investigate whether seasonal differences in ambient temperature affect the incidence of early postoperative cognitive dysfunction(POCD)among elderly patients undergoing laparoscopic surgery in tropical r...BACKGROUND To investigate whether seasonal differences in ambient temperature affect the incidence of early postoperative cognitive dysfunction(POCD)among elderly patients undergoing laparoscopic surgery in tropical regions.Additionally,it explored the perioperative risk factors associated with early POCD following abdominal laparoscopic surgery.AIM To investigate the influence of seasonal differences in ambient temperature on POCD of elderly patients METHODS A total of 125 patients aged≥65 years from Hainan Province,China,who underwent laparoscopic surgery under general anesthesia with tracheal intubation,were enrolled. All patients completed the Mini-Mental State Examination one day before surgery and onpostoperative days 1, 3, and 7. A decline of ≥ 2 points from baseline was considered indicative of cognitivedysfunction. Serum levels of S100 calcium binding protein B and neuron-specific enolase were measured usingenzyme-linked immunosorbent assay at three time points: Preoperatively, immediately after extubation, and 24hours postoperatively. Perioperative clinical data were collected to identify potential risk factors for POCD.Propensity score matching (PSM) was performed (1:1, caliper = 0.03), resulting in 41 matched patient pairs betweenwinter and summer groups.RESULTSAfter PSM, baseline characteristics including age, gender, body mass index, education level, comorbidities, andsurgical variables were well balanced between groups. There were no significant differences in the incidence ofPOCD on postoperative days 1, 3, and 7 between patients undergoing laparoscopic surgery in winter vs summer.However, multivariable logistic regression revealed that surgical duration (day 1, P value = 0.049), advanced ageand elevated creatinine (day 3, P value = 0.044, P value = 0.008), and hypoalbuminemia (day 3, P value = 0.042;day7, P value = 0.015) were independently associated with early POCD.CONCLUSIONAmbient temperature differences between winter and summer in tropical regions did not significantly affect theincidence of early POCD in elderly patients undergoing laparoscopic surgery. Nonetheless, age, longer surgicalduration, elevated creatinine, and hypoalbuminemia emerged as key risk factors. These findings underscore theimportance of perioperative optimization to reduce the risk of POCD in elderly patients, regardless of seasonaltemperature variations.展开更多
BACKGROUND Diabetic cognitive dysfunction(DCD)is one of the chronic complications of diabetes,but its mechanism is currently unknown.Studies have shown that mitochondrial fission mediated by calcium overload is an imp...BACKGROUND Diabetic cognitive dysfunction(DCD)is one of the chronic complications of diabetes,but its mechanism is currently unknown.Studies have shown that mitochondrial fission mediated by calcium overload is an important mechanism of DCD.Blocking calcium overload and restoring calcium homeostasis are key steps in treatment.Transient receptor potential melastatin 7(TRPM7)is a novel player in causing calcium overload.Our previous studies have shown that genetic silencing of TRPM7 in type 1 diabetic rats leads to significant improvements in cognitive function,but the specific mechanism remains unclear.Troxerutin,extracted from the flowers of Sophora japonica,is one of the derivatives of rutin and has been shown to have neuroprotective effects.However,its association with TRPM7 remains unclear.AIM To use animal and cellular models,we investigated whether TRPM7 mediated mitochondrial fission by upregulation of calcineurin(CaN)/dynamin-related protein 1(Drp1)ser637 in DCD,and whether Troxerutin improved DCD by inhibiting TRPM7-mediated mitochondrial division.METHODS In this study,we used db/db mice and hippocampal neuronal cell lines(HT22)treated with high-concentration glucose as our study subjects.We evaluated cognitive function using Morris water maze,novel object recognition tasks,and Nesting tests.We observed mitochondrial morphology using transmission electron microscopy and measured mitochondrial energy metabolism indicators using a spectrophotometer.We also detected mRNA and protein expression of TRPM7,CaN,p-Drp1^(ser637),caspase-3,B-cell lymphoma 2 associated X protein,and B-cell lymphoma 2 using quantitative real-time polymerase chain reaction,western blotting,and immunofluorescence.RESULTS In the db/db diabetic mice with cognitive dysfunction,as well as in hippocampal neurons exposed to high-concentration glucose,TRPM7 and CaN expression were upregulated,phosphorylated Drp1^(ser637)expression was downregulated,and mitochondrial fission was increased.By modulating(inhibiting or overexpressing)TRPM7,it was further validated that TRPM7 activates the CaN/Drp1^(ser637)pathway,resulting in an increase in mitochondrial fission and neuronal cell apoptosis.Troxerutin downregulated TRPM7/CaN/Drp1^(ser637),reduced mitochondrial fission,and improved DCD.CONCLUSION TRPM7 promotes mitochondrial fission via the CaN/Drp1^(ser637)pathway.Troxerutin improves mitochondrial function and reduces neuronal damage by inhibiting this pathway,suggesting TRPM7 as a potential therapeutic target for DCD.展开更多
BACKGROUND Diabetes is associated with increased cognitive decline and dementia due to the loss of myelinated nerve fiber function,which is linked to oligodendrocyte dysfunction.The voltage-gated proton channel 1(Hv1)...BACKGROUND Diabetes is associated with increased cognitive decline and dementia due to the loss of myelinated nerve fiber function,which is linked to oligodendrocyte dysfunction.The voltage-gated proton channel 1(Hv1)is important for the cellular proton extrusion machinery.However,its role in regulating diabetesinduced cognitive dysfunction is unclear.AIM To investigate the role of Hv1 in cognitive impairment induced by diabetes and its potential mechanisms,focusing on neuroinflammation,oligodendrocyte apoptosis,and axonal demyelination.METHODS A diabetes model was established by administering a high-fat diet and streptozotocin injections in mice.Hv1 knockout(KO)and wild-type mice were used to evaluate cognitive function via behavioral tests and neuroinflammation using immunofluorescence.Oligodendrocyte apoptosis was assessed with the terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay, and axonal demyelination wasanalyzed using electron microscopy.RESULTSHv1 expression was significantly increased in the corpus callosum of diabetic mice. Hv1 KO alleviated cognitiveimpairment, reduced oligodendrocyte apoptosis, and decreased the expression of inflammatory factors, includinginterleukin-1 and tumor necrosis factor-α, in diabetic mice. Electron microscopy revealed a reduction in myelinthickness and an increased g-ratio in diabetic mice, which were reversed by Hv1 KO.CONCLUSIONHv1 plays a role in diabetes-induced cognitive dysfunction by modulating neuroinflammation and myelinintegrity. Hv1 KO demonstrates therapeutic potential in mitigating diabetes-related cognitive decline andassociated complications.展开更多
Postoperative cognitive dysfunction is a typical complication,which can be referred to as POCD.This complication is common in elderly patients.Among them,POCD is mainly manifested in the function of patients with atte...Postoperative cognitive dysfunction is a typical complication,which can be referred to as POCD.This complication is common in elderly patients.Among them,POCD is mainly manifested in the function of patients with attention deficit and memory reduction after surgery,among which serious patients are prone to personality change,which affects their social behavior ability.In the context of the current era,the cause of POCD is not clear,combined with the results of most studies,it is found that central nervous inflammation,is a key factor affecting POCD.From the perspective of central inflammation,this paper analyzes the relationship between central inflammation and POCD,and discusses the mechanism of action,aiming at effectively preventing and treating POCD and providing a reference for subsequent research in related fields.展开更多
Postoperative cognitive dysfunction(POCD)remains a major issue that worsens the prognosis of elderly surgery patients.This article reviews the current research on the effect of different anesthesia methods and commonl...Postoperative cognitive dysfunction(POCD)remains a major issue that worsens the prognosis of elderly surgery patients.This article reviews the current research on the effect of different anesthesia methods and commonly utilized anesthetics on the incidence of POCD in elderly patients,aiming to provide an understanding of the underlying mechanisms contributing to this condition and facilitate the development of more reasonable anesthesia protocols,ultimately reducing the incidence of POCD in elderly surgery patients.展开更多
BACKGROUND With the continuous growth of the modern elderly population,the risk of fracture increases.Hip fracture is a common type of fracture in older people.Total hip arthroplasty(THA)has significant advantages in ...BACKGROUND With the continuous growth of the modern elderly population,the risk of fracture increases.Hip fracture is a common type of fracture in older people.Total hip arthroplasty(THA)has significant advantages in relieving chronic pain and promoting the recovery of hip joint function.AIM To investigate the effect of ulinastatin combined with dexmedetomidine(Dex)on the incidences of postoperative cognitive dysfunction(POCD)and emergence agitation in elderly patients who underwent THA.METHODS A total of 397 patients who underwent THA from February 2019 to August 2022.We conducted a three-year retrospective cohort study in Shaanxi Provincial People’s Hospital.Comprehensive demographic data were obtained from the electronic medical record system.We collected preoperative,intraoperative,and postoperative data.One hundred twenty-nine patients who were administered Dex during the operation were included in the Dex group.One hundred fifty patients who were intravenously injected with ulinastatin 15 min before anesthesia induction were included in the ulinastatin group.One hundred eighteen patients who were administered ulinastatin combined with Dex during the operation were included in the Dex+ulinastatin group.The patients’perioperative conditions,hemodynamic indexes,postoperative Mini-Mental State Examination(MMSE)scores,Ramsay score,incidence of POCD,and serum inflammatory cytokines were evaluated.RESULTS There was a significant difference in the 24 h visual analogue scale score among the three groups,and the score in the Dex+ulinastatin group was the lowest(P<0.05).Compared with the Dex and ulinastatin group,the MMSE scores of the Dex+ulinastatin group were significantly increased at 1 and 7 d after the operation(all P<0.05).Compared with those in the Dex and ulinastatin groups,incidence of POCD,levels of serum inflammatory cytokines in the Dex+ulinastatin group were significantly decreased at 1 and 7 d after the operation(all P<0.05).The observer’s assessment of the alertness/sedation score and Ramsay score of the Dex+ulinastatin group were significantly different from those of the Dex and ulinastatin groups on the first day after the operation(all P<0.05).CONCLUSION Ulinastatin combined with Dex can prevent the occurrence of POCD and emergence agitation in elderly patients undergoing THA.展开更多
BACKGROUND Postoperative pain management and cognitive function preservation are crucial for patients undergoing thoracoscopic surgery for lung cancer(LC).This is achieved using either a thoracic paravertebral block(T...BACKGROUND Postoperative pain management and cognitive function preservation are crucial for patients undergoing thoracoscopic surgery for lung cancer(LC).This is achieved using either a thoracic paravertebral block(TPVB)or sufentanil(SUF)-based multimodal analgesia.However,the efficacy and impact of their combined use on postoperative pain and postoperative cognitive dysfunction(POCD)remain unclear.AIM To explore the analgesic effect and the influence on POCD of TPVB combined with SUF-based multimodal analgesia in patients undergoing thoracoscopic radical resection for LC to help optimize postoperative pain management and improve patient outcomes.METHODS This retrospective analysis included 107 patients undergoing thoracoscopic radical resection for LC at The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital between May 2021 and January 2023.Patients receiving SUF-based multimodal analgesia(n=50)and patients receiving TPVB+SUF-based multimodal analgesia(n=57)were assigned to the control group and TPVB group,respectively.We compared the Ramsay Sedation Scale and visual analog scale(VAS)scores at rest and with cough between the two groups at 2,12,and 24 h after surgery.Serum levels of epinephrine(E),angio-tensin Ⅱ(Ang Ⅱ),norepinephrine(NE),superoxide dismutase(SOD),vascular endothelial growth factor(VEGF),transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),and S-100 calcium-binding proteinβ(S-100β)were measured before and 24 h after surgery.The Mini-Mental State Examination(MMSE)was administered 1 day before surgery and at 3 and 5 days after surgery,and the occurrence of POCD was monitored for 5 days after surgery.Adverse reactions were also recorded.RESULTS There were no significant time point,between-group,and interaction effects in Ramsay sedation scores between the two groups(P>0.05).Significantly,there were notable time point effects,between-group differences,and interaction effects observed in VAS scores both at rest and with cough(P<0.05).The VAS scores at rest and with cough at 12 and 24 h after surgery were lower than those at 2 h after surgery and gradually decreased as postoperative time increased(P<0.05).The TPVB group had lower VAS scores than the control group at 2,12,and 24 h after surgery(P<0.05).The MMSE scores at postoperative days 1 and 3 were markedly higher in the TPVB group than in the control group(P<0.05).The incidence of POCD was significantly lower in the TPVB group than in the control group within 5 days after surgery(P<0.05).Both groups had elevated serum E,Ang Ⅱ,and NE and decreased serum SOD levels at 24 h after surgery compared with the preoperative levels,with better indices in the TPVB group(P<0.05).Marked elevations in serum levels of VEGF,TGF-β1,TNF-α,and S-100β were observed in both groups at 24 h after surgery,with lower levels in the TPVB group than in the control group(P<0.05).CONCLUSION TPVB combined with SUF-based multimodal analgesia further relieves pain in patients undergoing thoracoscopic radical surgery for LC,enhances analgesic effects,reduces postoperative stress response,and inhibits postoperative increases in serum VEGF,TGF-β1,TNF-α,and S-100β levels.This scheme also reduced POCD and had a high safety profile.展开更多
Diabetes-associated cognitive dysfunction has already been attracted considerable attention.Advanced glycation end products(AGEs)from daily diets are thought to be a vital contributor to the development of this diseas...Diabetes-associated cognitive dysfunction has already been attracted considerable attention.Advanced glycation end products(AGEs)from daily diets are thought to be a vital contributor to the development of this diseases.However,the effect of one of the best-characterized exogenous AGEs N^(ε)-(carboxymethyl)lysine(CML)on cognitive function is not fully reported.In the present study,diabetical Goto-Kakizaki(GK)rats were treated with free CML for 8-weeks.It was found that oral consumption of exogenous CML significantly aggravated diabetes-associated cognitive dysfunction in behavioral test.In details,exogenous CML increased levels of oxidative stress,promoted the activation of glial cells in the brain,up-regulated the release of inflammatory cytokines interleukin-6,inhibited the protein expression of the brain-derived neurotrophic factor and thus led to neuroinflammation.Furthermore,exogenous CML promoted the amyloidogenesis in the brain of GK rats,and inhibited the expression of GLUT4.Additionally,several tricarboxylic acid cycle and glutamate-glutamine/γ-aminobutyric acid cycle intermediates including pyruvate,succinic acid,glutamine,glutamate were significantly changed in brain of GK rats treated with exogenous free CML.In conclusion,exogenous free CML is a potentially noxious compounds led to aggravated diabetes-associated cognitive dysfunction which could be possibly explained by its effects on neuroinflammation,energy and neurotransmitter amino acid homeostasis.展开更多
Memory deficit,which is often associated with aging and many psychiatric,neurological,and neurodegenerative diseases,has been a challenging issue for treatment.Up till now,all potential drug candidates have failed to ...Memory deficit,which is often associated with aging and many psychiatric,neurological,and neurodegenerative diseases,has been a challenging issue for treatment.Up till now,all potential drug candidates have failed to produce satisfa ctory effects.Therefore,in the search for a solution,we found that a treatment with the gene corresponding to the RGS14414protein in visual area V2,a brain area connected with brain circuits of the ventral stream and the medial temporal lobe,which is crucial for object recognition memory(ORM),can induce enhancement of ORM.In this study,we demonstrated that the same treatment with RGS14414in visual area V2,which is relatively unaffected in neurodegenerative diseases such as Alzheimer s disease,produced longlasting enhancement of ORM in young animals and prevent ORM deficits in rodent models of aging and Alzheimer’s disease.Furthermore,we found that the prevention of memory deficits was mediated through the upregulation of neuronal arbo rization and spine density,as well as an increase in brain-derived neurotrophic factor(BDNF).A knockdown of BDNF gene in RGS14414-treated aging rats and Alzheimer s disease model mice caused complete loss in the upregulation of neuronal structural plasticity and in the prevention of ORM deficits.These findings suggest that BDNF-mediated neuronal structural plasticity in area V2 is crucial in the prevention of memory deficits in RGS14414-treated rodent models of aging and Alzheimer’s disease.Therefore,our findings of RGS14414gene-mediated activation of neuronal circuits in visual area V2 have therapeutic relevance in the treatment of memory deficits.展开更多
Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-βdeposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive ...Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-βdeposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive deficits.Furthermore,traumatic brain injury can exacerbate Alzheimer's disease-like pathologies,potentially leading to the development of Alzheimer's disease.Nanocarriers offer a potential solution by facilitating the delive ry of small interfering RNAs across the blood-brain barrier for the targeted silencing of key pathological genes implicated in traumatic brain injury and Alzheimer's disease.U nlike traditional approaches to neuro regeneration,this is a molecula r-targeted strategy,thus avoiding non-specific drug actions.This review focuses on the use of nanocarrier systems for the efficient and precise delive ry of siRNAs,discussing the advantages,challenges,and future directions.In principle,siRNAs have the potential to target all genes and non-targetable protein s,holding significant promise for treating various diseases.Among the various therapeutic approaches currently available for neurological diseases,siRNA gene silencing can precisely"turn off"the expression of any gene at the genetic level,thus radically inhibiting disease progression;however,a significant challenge lies in delivering siRNAs across the blood-brain barrier.Nanoparticles have received increasing attention as an innovative drug delive ry tool fo r the treatment of brain diseases.They are considered a potential therapeutic strategy with the advantages of being able to cross the blood-brain barrier,targeted drug delivery,enhanced drug stability,and multifunctional therapy.The use of nanoparticles to deliver specific modified siRNAs to the injured brain is gradually being recognized as a feasible and effective approach.Although this strategy is still in the preclinical exploration stage,it is expected to achieve clinical translation in the future,creating a new field of molecular targeted therapy and precision medicine for the treatment of Alzheimer's disease associated with traumatic brain injury.展开更多
Alzheimer’s disease,a devastating neurodegenerative disorder,is characterized by progressive cognitive decline,primarily due to amyloid-beta protein deposition and tau protein phosphorylation.Effectively reducing the...Alzheimer’s disease,a devastating neurodegenerative disorder,is characterized by progressive cognitive decline,primarily due to amyloid-beta protein deposition and tau protein phosphorylation.Effectively reducing the cytotoxicity of amyloid-beta42 aggregates and tau oligomers may help slow the progression of Alzheimer’s disease.Conventional drugs,such as donepezil,can only alleviate symptoms and are not able to prevent the underlying pathological processes or cognitive decline.Currently,active and passive immunotherapies targeting amyloid-beta and tau have shown some efficacy in mice with asymptomatic Alzheimer’s disease and other transgenic animal models,attracting considerable attention.However,the clinical application of these immunotherapies demonstrated only limited efficacy before the discovery of lecanemab and donanemab.This review first discusses the advancements in the pathogenesis of Alzheimer’s disease and active and passive immunotherapies targeting amyloid-beta and tau proteins.Furthermore,it reviews the advantages and disadvantages of various immunotherapies and considers their future prospects.Although some antibodies have shown promise in patients with mild Alzheimer’s disease,substantial clinical data are still lacking to validate their effectiveness in individuals with moderate Alzheimer’s disease.展开更多
Sleep disorders,particularly insomnia,have emerged as a critical public health challenge,with the situation worsened by the coronavirus disease-2019 pandemic.Insomnia symptoms,which affected up to 45%of the population...Sleep disorders,particularly insomnia,have emerged as a critical public health challenge,with the situation worsened by the coronavirus disease-2019 pandemic.Insomnia symptoms,which affected up to 45%of the population during this period,highlight the urgent need to understand the mechanisms linking sleep disturbances to mental health outcomes.Recent findings suggest that cognitive failures,such as memory lapses and attentional deficits,mediate the relationship between insomnia and emotional disorders such as anxiety and depression.The role of personality traits,particularly neuroticism,adds further complexity,as it may either exacerbate or buffer these effects under specific conditions.This review explores the study by Li et al,which offers valuable insights into the cognitive-emotional pathways influenced by sleep disturbances.The study makes significant contributions by identifying key cognitive mechanisms and proposing the dual role of neuroticism in shaping emotional outcomes.To advance these findings,this letter advocates for future longitudinal research and the integration of targeted interventions,such as cognitive-behavioral therapy for insomnia,into public health frameworks.By addressing insomnia-induced cognitive dysfunction,these strategies can enhance emotional regulation and foster resilience,particularly in vulnerable populations facing the mental health impacts of the pandemic.展开更多
This article discusses a study by Li et al,which investigates the role of the microglial voltage-gated proton channel 1(Hv1)in diabetes-related cognitive decline.The authors showed that Hv1 is upregulated in the corpu...This article discusses a study by Li et al,which investigates the role of the microglial voltage-gated proton channel 1(Hv1)in diabetes-related cognitive decline.The authors showed that Hv1 is upregulated in the corpus callosum of diabetic mice and that its knockout improves working memory,reduces microglial production of interleukin-1βand tumour necrosis factor alpha,and decreases apoptosis of oligodendrocyte progenitor cells.Furthermore,electron microscopy revealed that the myelin thickness and the g-ratio were preserved in Hv1 knockout mice,remaining within normal limits.In addition,Hv1 knockdown mitigated interleukin-1βsecretion and suppressed ferroptosis markers(ferritin heavy chain/ferritin light chain,CCAAT/enhancer binding protein homologous protein,glucose-regulated protein 78,etc.)in vitro,suggesting the involvement of an Hv1-reactive oxygen species-glucose-regulated protein 78 axis in diabetic demyelination.We highlight the translational implications of these findings and recommend future studies employing microglia-specific Hv1 deletion models,longitudinal cognitive assessments and preclinical evaluation of pharmacological Hv1 inhibitors.展开更多
Objective:To investigate whether nacre extract improves insulin sensitivity,brain glucose metabolism,and cognitive function in diabetic mice.Methods:Diabetic KK-Ay mice(n=5/group)were fed a standard diet or diets supp...Objective:To investigate whether nacre extract improves insulin sensitivity,brain glucose metabolism,and cognitive function in diabetic mice.Methods:Diabetic KK-Ay mice(n=5/group)were fed a standard diet or diets supplemented with nacre extract(125 or 250 mg/kg)for 13 weeks.Metabolic status was assessed by measuring fasting glucose and insulin levels,HOMA-IR,glucose tolerance,and insulin tolerance.The expression of IRS-1,IRS-2,and GLUT4 in the brain was analyzed by qPCR,Western blotting,and immunohistochemistry.Cognitive and anxiety-like behaviors were evaluated using the Y-maze,novel object recognition,Barnes maze,and open field tests.Results:Nacre extract significantly reduced fasting glucose and insulin levels,improved HOMA-IR,and enhanced glucose and insulin tolerance(P<0.05)in diabetic mice.It also restored GLUT4 expression and significantly upregulated SIRT1 and BDNF.Behavioral assessments showed significant improvements in memory and reduced anxiety-like behaviors.Conclusions:Nacre extract enhances insulin sensitivity,improves brain glucose metabolism,and alleviates cognitive and emotional dysfunction in diabetic mice.Further studies are warranted to verify the exact molecular mechanisms and efficacy of nacre extract in diabetes-associated metabolic and neurocognitive dysfunction.展开更多
OBJECTIVE:To explore the effect of Traditional Chinese Medicine(TCM)constitution on cognitive impairment(CI)in patients with cerebral small vessel disease(CSVD)and its underlying neuroimaging mechanism and to provide ...OBJECTIVE:To explore the effect of Traditional Chinese Medicine(TCM)constitution on cognitive impairment(CI)in patients with cerebral small vessel disease(CSVD)and its underlying neuroimaging mechanism and to provide countermeasures for health management of CSVD patients.METHODS:A total of 241 CSVD patients were recruited from the Department of Neurology.All subjects underwent head magnetic resonance imaging(MRI),Chinese Medicine Questionnaire(CCMQ)and cognitive function examination.The CSVD patients were divided according to the Montreal Cognitive Assessment(MoCA)score into a normal cognitive group(73 cases)and a CI group(168 cases).Logistic regression was used to analyse the risk constitution of CSVD-CI and to construct a risk prediction model.3DT1 MRI images and FreeSurfer 6.0 software(Athinoula A.Martinos,Boston,MA,USA)were used to further explore the involvement of hippocampal subregion volume in patients with at-risk constitution and its correlation with cognitive function.RESULTS:Logistic regression analysis showed that Yang-deficiency constitution(YADC)(P=0.020),older age(P=0.008)and hypertension(P=0.011)were risk factors for CSVD-CI but that balanced constitution(P=0.003)and education(P<0.001)were protective factors.A receiver operating characteristic curve(ROC)was drawn,and the area under the curve was 0.820.Further comparison of overall hippocampal and 12 hippocampal subregion volumes between YADC and non-YADC patients revealed decreased total volume of the left and right hippocampus,bilateral subiculum,presubiculum,molecular layer and right fimbria in the YADC group(P<0.05/13,13 is the number of hypothesis tests).Moreover,in the YADC group,the cognitive function of CSVD patients correlated positively with the overall volume of the left hippocampus(r=0.304,P<0.05)and the molecular layer volume of the left hippocampus(r=0.288,P<0.05).CONCLUSION:CSVD patients with YADC are more prone towards developing CI,and asymmetric atrophy of the hippocampus might be the underlying neuroimaging mechanism.In particular,the volume of the left whole hippocampus and the left hippocampal molecular layer correlated significantly with general cognitive function.展开更多
Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The...Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The long noncoding RNA growth arrest-specific 5(GAS5) is a member of the 5′-terminal oligopyrimidine gene family that may be involved in neurological disorders, but its role in Alzheimer's disease remains unclear. This study aimed to investigate the function of GAS5 and construct a GAS5-associated competitive endogenous RNA network comprising potential targets. RNA sequencing results showed that GAS5 was upregulated in five familial Alzheimer's disease(5×FAD) mice, APPswe/PSEN1dE9(APP/PS1) mice, Alzheimer's disease-related APPswe cells, and serum from patients with Alzheimer's disease. Functional experiments with targeted overexpression and silencing demonstrated that GAS5 played a role in cognitive dysfunction and multiple Alzheimer's disease-associated pathologies, including tau hyperphosphorylation, amyloid-beta accumulation, and neuronal apoptosis. Mechanistic studies indicated that GAS5 acted as an endogenous sponge by competing for microRNA-23b-3p(miR-23b-3p) binding to regulate its targets glycogen synthase kinase 3beta(GSK-3β) and phosphatase and tensin homologue deleted on chromosome 10(PTEN) expression in an Argonaute 2-induced RNA silencing complex(RISC)-dependent manner. GAS5 inhibited miR-23b-3p-mediated GSK-3β and PTEN cascades with a feedforward PTEN/protein kinase B(Akt)/GSK-3β linkage. Furthermore, recovery of GAS5/miR-23b-3p/GSK-3β/PTEN pathways relieved Alzheimer's disease-like symptoms in vivo, indicated by the amelioration of spatial cognition, neuronal degeneration, amyloid-beta load, and tau phosphorylation. Together, these findings suggest that GAS5 promotes Alzheimer's disease pathogenesis. This study establishes the functional convergence of the GAS5/miR-23b-3p/GSK-3β/PTEN pathway on multiple pathologies, suggesting a candidate therapeutic target in Alzheimer's disease.展开更多
Objective:Investigating the effects and molecular mechanisms of nursing interventions based on environmental enrichment on cognitive function in ischemic stroke rats.Methods:A total of 30 Sprague-Dawley(SD)rats belong...Objective:Investigating the effects and molecular mechanisms of nursing interventions based on environmental enrichment on cognitive function in ischemic stroke rats.Methods:A total of 30 Sprague-Dawley(SD)rats belonging to the same batch were randomly divided into 3 groups(n=10)using a random number table:Sham Surgery Control Group(Sham),Ischemia-Reperfusion(I/R)Group,and Ischemia-Reperfusion Group with Environmental Enrichment Intervention(I/R+EEI).The expression levels of brain-derived neurotrophic factor(BDNF)protein in the hippocampus region were measured and compared among different groups.Results:Compared with the Sham group,the I/R group showed significantly reduced learning and memory abilities,with notably lower BDNF levels(P<0.05).Compared to the I/R group,the I/R+EEI group exhibited significantly improved learning and memory abilities as well as increased BDNF protein levels(P<0.05).Conclusions:Abnormal BDNF protein secretion may be the molecular mechanism of cognitive dysfunction due to hippocampal neuronal damage in ischemia-reperfusion,and modifying this neurotransmitter’s secretion can effectively improve cognitive function in ischemia-reperfusion rats.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81730033,82171193(to XG)the Key Talent Project for Strengthening Health during the 13^(th)Five-Year Plan Period,No.ZDRCA2016069(to XG)+1 种基金the National Key R&D Program of China,No.2018YFC2001901(to XG)Jiangsu Provincial Medical Key Discipline,No.ZDXK202232(to XG)。
文摘Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.
基金Supported by the Research Fund of Qiannan Medical College for Nationalities,No.Qnyz202222.
文摘BACKGROUND Colorectal cancer(CRC)is one of the most prevalent and lethal malignant tumors worldwide.Currently,surgical intervention was the primary treatment modality for CRC.However,increasing studies have revealed that CRC patients may experience postoperative cognitive dysfunction(POCD).AIM To establish a risk prediction model for POCD in CRC patients and investigate the preventive value of dexmedetomidine(DEX).METHODS A retrospective analysis was conducted on clinical data from 140 CRC patients who underwent surgery at the People’s Hospital of Qian Nan from February 2020 to May 2024.Patients were allocated into a modeling group(n=98)and a validation group(n=42)in a 7:3 ratio.General clinical data were collected.Additionally,in the modeling group,patients who received DEX preoperatively were incorporated into the observation group(n=54),while those who did not were placed in the control group(n=44).The incidence of POCD was recorded for both cohorts.Data analysis was performed using statistical product and service solutions 20.0,with t-tests orχ^(2) tests employed for group comparisons based on the data type.Least absolute shrinkage and selection operator regression was applied to identify influencing factors and reduce the impact of multicollinear predictors among variables.Multivariate analysis was carried out using Logistic regression.Based on the identified risk factors,a risk prediction model for POCD in CRC patients was developed,and the predictive value of these risk factors was evaluated.RESULTS Significant differences were observed between the cognitive dysfunction group and the non-cognitive dysfunction group in diabetes status,alcohol consumption,years of education,anesthesia duration,intraoperative blood loss,intraoperative hypoxemia,use of DEX during surgery,intraoperative use of vasoactive drugs,surgical time,systemic inflammatory response syndrome(SIRS)score(P<0.05).Multivariate Logistic regression analysis identified that diabetes[odds ratio(OR)=4.679,95%confidence interval(CI)=1.382-15.833],alcohol consumption(OR=5.058,95%CI:1.255-20.380),intraoperative hypoxemia(OR=4.697,95%CI:1.380-15.991),no use of DEX during surgery(OR=3.931,95%CI:1.383-11.175),surgery duration≥90 minutes(OR=4.894,95%CI:1.377-17.394),and a SIRS score≥3(OR=4.133,95%CI:1.323-12.907)were independent risk factors for POCD in CRC patients(P<0.05).A risk prediction model for POCD was constructed using diabetes,alcohol consumption,intraoperative hypoxemia,non-use of DEX during surgery,surgery duration,and SIRS score as factors.A receiver operator characteristic curve analysis of these factors revealed the model’s predictive sensitivity(88.56%),specificity(70.64%),and area under the curve(AUC)(AUC=0.852,95%CI:0.773-0.919).The model was validated using 42 CRC patients who met the inclusion criteria,demonstrating sensitivity(80.77%),specificity(81.25%),and accuracy(80.95%),and AUC(0.805)in diagnosing cognitive impairment,with a 95%CI:0.635-0.896.CONCLUSION Logistic regression analysis identified that diabetes,alcohol consumption,intraoperative hypoxemia,non-use of DEX during surgery,surgery duration,and SIRS score vigorously influenced the occurrence of POCD.The risk prediction model based on these factors demonstrated good predictive performance for POCD in CRC individuals.This study offers valuable insights for clinical practice and contributes to the prevention and management of POCD under CRC circumstances.
文摘BACKGROUND To investigate whether seasonal differences in ambient temperature affect the incidence of early postoperative cognitive dysfunction(POCD)among elderly patients undergoing laparoscopic surgery in tropical regions.Additionally,it explored the perioperative risk factors associated with early POCD following abdominal laparoscopic surgery.AIM To investigate the influence of seasonal differences in ambient temperature on POCD of elderly patients METHODS A total of 125 patients aged≥65 years from Hainan Province,China,who underwent laparoscopic surgery under general anesthesia with tracheal intubation,were enrolled. All patients completed the Mini-Mental State Examination one day before surgery and onpostoperative days 1, 3, and 7. A decline of ≥ 2 points from baseline was considered indicative of cognitivedysfunction. Serum levels of S100 calcium binding protein B and neuron-specific enolase were measured usingenzyme-linked immunosorbent assay at three time points: Preoperatively, immediately after extubation, and 24hours postoperatively. Perioperative clinical data were collected to identify potential risk factors for POCD.Propensity score matching (PSM) was performed (1:1, caliper = 0.03), resulting in 41 matched patient pairs betweenwinter and summer groups.RESULTSAfter PSM, baseline characteristics including age, gender, body mass index, education level, comorbidities, andsurgical variables were well balanced between groups. There were no significant differences in the incidence ofPOCD on postoperative days 1, 3, and 7 between patients undergoing laparoscopic surgery in winter vs summer.However, multivariable logistic regression revealed that surgical duration (day 1, P value = 0.049), advanced ageand elevated creatinine (day 3, P value = 0.044, P value = 0.008), and hypoalbuminemia (day 3, P value = 0.042;day7, P value = 0.015) were independently associated with early POCD.CONCLUSIONAmbient temperature differences between winter and summer in tropical regions did not significantly affect theincidence of early POCD in elderly patients undergoing laparoscopic surgery. Nonetheless, age, longer surgicalduration, elevated creatinine, and hypoalbuminemia emerged as key risk factors. These findings underscore theimportance of perioperative optimization to reduce the risk of POCD in elderly patients, regardless of seasonaltemperature variations.
基金Supported by the Natural Science Foundation of Hebei Province,No.H2021206187 and No.H2021206452.
文摘BACKGROUND Diabetic cognitive dysfunction(DCD)is one of the chronic complications of diabetes,but its mechanism is currently unknown.Studies have shown that mitochondrial fission mediated by calcium overload is an important mechanism of DCD.Blocking calcium overload and restoring calcium homeostasis are key steps in treatment.Transient receptor potential melastatin 7(TRPM7)is a novel player in causing calcium overload.Our previous studies have shown that genetic silencing of TRPM7 in type 1 diabetic rats leads to significant improvements in cognitive function,but the specific mechanism remains unclear.Troxerutin,extracted from the flowers of Sophora japonica,is one of the derivatives of rutin and has been shown to have neuroprotective effects.However,its association with TRPM7 remains unclear.AIM To use animal and cellular models,we investigated whether TRPM7 mediated mitochondrial fission by upregulation of calcineurin(CaN)/dynamin-related protein 1(Drp1)ser637 in DCD,and whether Troxerutin improved DCD by inhibiting TRPM7-mediated mitochondrial division.METHODS In this study,we used db/db mice and hippocampal neuronal cell lines(HT22)treated with high-concentration glucose as our study subjects.We evaluated cognitive function using Morris water maze,novel object recognition tasks,and Nesting tests.We observed mitochondrial morphology using transmission electron microscopy and measured mitochondrial energy metabolism indicators using a spectrophotometer.We also detected mRNA and protein expression of TRPM7,CaN,p-Drp1^(ser637),caspase-3,B-cell lymphoma 2 associated X protein,and B-cell lymphoma 2 using quantitative real-time polymerase chain reaction,western blotting,and immunofluorescence.RESULTS In the db/db diabetic mice with cognitive dysfunction,as well as in hippocampal neurons exposed to high-concentration glucose,TRPM7 and CaN expression were upregulated,phosphorylated Drp1^(ser637)expression was downregulated,and mitochondrial fission was increased.By modulating(inhibiting or overexpressing)TRPM7,it was further validated that TRPM7 activates the CaN/Drp1^(ser637)pathway,resulting in an increase in mitochondrial fission and neuronal cell apoptosis.Troxerutin downregulated TRPM7/CaN/Drp1^(ser637),reduced mitochondrial fission,and improved DCD.CONCLUSION TRPM7 promotes mitochondrial fission via the CaN/Drp1^(ser637)pathway.Troxerutin improves mitochondrial function and reduces neuronal damage by inhibiting this pathway,suggesting TRPM7 as a potential therapeutic target for DCD.
基金Supported by the National Natural Science Foundation of China,No.82300894.
文摘BACKGROUND Diabetes is associated with increased cognitive decline and dementia due to the loss of myelinated nerve fiber function,which is linked to oligodendrocyte dysfunction.The voltage-gated proton channel 1(Hv1)is important for the cellular proton extrusion machinery.However,its role in regulating diabetesinduced cognitive dysfunction is unclear.AIM To investigate the role of Hv1 in cognitive impairment induced by diabetes and its potential mechanisms,focusing on neuroinflammation,oligodendrocyte apoptosis,and axonal demyelination.METHODS A diabetes model was established by administering a high-fat diet and streptozotocin injections in mice.Hv1 knockout(KO)and wild-type mice were used to evaluate cognitive function via behavioral tests and neuroinflammation using immunofluorescence.Oligodendrocyte apoptosis was assessed with the terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay, and axonal demyelination wasanalyzed using electron microscopy.RESULTSHv1 expression was significantly increased in the corpus callosum of diabetic mice. Hv1 KO alleviated cognitiveimpairment, reduced oligodendrocyte apoptosis, and decreased the expression of inflammatory factors, includinginterleukin-1 and tumor necrosis factor-α, in diabetic mice. Electron microscopy revealed a reduction in myelinthickness and an increased g-ratio in diabetic mice, which were reversed by Hv1 KO.CONCLUSIONHv1 plays a role in diabetes-induced cognitive dysfunction by modulating neuroinflammation and myelinintegrity. Hv1 KO demonstrates therapeutic potential in mitigating diabetes-related cognitive decline andassociated complications.
基金Jiangsu University Student Innovation and Entrepreneurship Project,“Study on the Mechanism of TLR4-mediated Central Inflammation Induced by Glial Cell Activation to POCD”(Project No.:202313980027Y)。
文摘Postoperative cognitive dysfunction is a typical complication,which can be referred to as POCD.This complication is common in elderly patients.Among them,POCD is mainly manifested in the function of patients with attention deficit and memory reduction after surgery,among which serious patients are prone to personality change,which affects their social behavior ability.In the context of the current era,the cause of POCD is not clear,combined with the results of most studies,it is found that central nervous inflammation,is a key factor affecting POCD.From the perspective of central inflammation,this paper analyzes the relationship between central inflammation and POCD,and discusses the mechanism of action,aiming at effectively preventing and treating POCD and providing a reference for subsequent research in related fields.
文摘Postoperative cognitive dysfunction(POCD)remains a major issue that worsens the prognosis of elderly surgery patients.This article reviews the current research on the effect of different anesthesia methods and commonly utilized anesthetics on the incidence of POCD in elderly patients,aiming to provide an understanding of the underlying mechanisms contributing to this condition and facilitate the development of more reasonable anesthesia protocols,ultimately reducing the incidence of POCD in elderly surgery patients.
文摘BACKGROUND With the continuous growth of the modern elderly population,the risk of fracture increases.Hip fracture is a common type of fracture in older people.Total hip arthroplasty(THA)has significant advantages in relieving chronic pain and promoting the recovery of hip joint function.AIM To investigate the effect of ulinastatin combined with dexmedetomidine(Dex)on the incidences of postoperative cognitive dysfunction(POCD)and emergence agitation in elderly patients who underwent THA.METHODS A total of 397 patients who underwent THA from February 2019 to August 2022.We conducted a three-year retrospective cohort study in Shaanxi Provincial People’s Hospital.Comprehensive demographic data were obtained from the electronic medical record system.We collected preoperative,intraoperative,and postoperative data.One hundred twenty-nine patients who were administered Dex during the operation were included in the Dex group.One hundred fifty patients who were intravenously injected with ulinastatin 15 min before anesthesia induction were included in the ulinastatin group.One hundred eighteen patients who were administered ulinastatin combined with Dex during the operation were included in the Dex+ulinastatin group.The patients’perioperative conditions,hemodynamic indexes,postoperative Mini-Mental State Examination(MMSE)scores,Ramsay score,incidence of POCD,and serum inflammatory cytokines were evaluated.RESULTS There was a significant difference in the 24 h visual analogue scale score among the three groups,and the score in the Dex+ulinastatin group was the lowest(P<0.05).Compared with the Dex and ulinastatin group,the MMSE scores of the Dex+ulinastatin group were significantly increased at 1 and 7 d after the operation(all P<0.05).Compared with those in the Dex and ulinastatin groups,incidence of POCD,levels of serum inflammatory cytokines in the Dex+ulinastatin group were significantly decreased at 1 and 7 d after the operation(all P<0.05).The observer’s assessment of the alertness/sedation score and Ramsay score of the Dex+ulinastatin group were significantly different from those of the Dex and ulinastatin groups on the first day after the operation(all P<0.05).CONCLUSION Ulinastatin combined with Dex can prevent the occurrence of POCD and emergence agitation in elderly patients undergoing THA.
文摘BACKGROUND Postoperative pain management and cognitive function preservation are crucial for patients undergoing thoracoscopic surgery for lung cancer(LC).This is achieved using either a thoracic paravertebral block(TPVB)or sufentanil(SUF)-based multimodal analgesia.However,the efficacy and impact of their combined use on postoperative pain and postoperative cognitive dysfunction(POCD)remain unclear.AIM To explore the analgesic effect and the influence on POCD of TPVB combined with SUF-based multimodal analgesia in patients undergoing thoracoscopic radical resection for LC to help optimize postoperative pain management and improve patient outcomes.METHODS This retrospective analysis included 107 patients undergoing thoracoscopic radical resection for LC at The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital between May 2021 and January 2023.Patients receiving SUF-based multimodal analgesia(n=50)and patients receiving TPVB+SUF-based multimodal analgesia(n=57)were assigned to the control group and TPVB group,respectively.We compared the Ramsay Sedation Scale and visual analog scale(VAS)scores at rest and with cough between the two groups at 2,12,and 24 h after surgery.Serum levels of epinephrine(E),angio-tensin Ⅱ(Ang Ⅱ),norepinephrine(NE),superoxide dismutase(SOD),vascular endothelial growth factor(VEGF),transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),and S-100 calcium-binding proteinβ(S-100β)were measured before and 24 h after surgery.The Mini-Mental State Examination(MMSE)was administered 1 day before surgery and at 3 and 5 days after surgery,and the occurrence of POCD was monitored for 5 days after surgery.Adverse reactions were also recorded.RESULTS There were no significant time point,between-group,and interaction effects in Ramsay sedation scores between the two groups(P>0.05).Significantly,there were notable time point effects,between-group differences,and interaction effects observed in VAS scores both at rest and with cough(P<0.05).The VAS scores at rest and with cough at 12 and 24 h after surgery were lower than those at 2 h after surgery and gradually decreased as postoperative time increased(P<0.05).The TPVB group had lower VAS scores than the control group at 2,12,and 24 h after surgery(P<0.05).The MMSE scores at postoperative days 1 and 3 were markedly higher in the TPVB group than in the control group(P<0.05).The incidence of POCD was significantly lower in the TPVB group than in the control group within 5 days after surgery(P<0.05).Both groups had elevated serum E,Ang Ⅱ,and NE and decreased serum SOD levels at 24 h after surgery compared with the preoperative levels,with better indices in the TPVB group(P<0.05).Marked elevations in serum levels of VEGF,TGF-β1,TNF-α,and S-100β were observed in both groups at 24 h after surgery,with lower levels in the TPVB group than in the control group(P<0.05).CONCLUSION TPVB combined with SUF-based multimodal analgesia further relieves pain in patients undergoing thoracoscopic radical surgery for LC,enhances analgesic effects,reduces postoperative stress response,and inhibits postoperative increases in serum VEGF,TGF-β1,TNF-α,and S-100β levels.This scheme also reduced POCD and had a high safety profile.
基金supported by the National Natural Science Foundation of China(32302258,32172317)Changsha Municipal Natural Science Foundation(kq2202223).
文摘Diabetes-associated cognitive dysfunction has already been attracted considerable attention.Advanced glycation end products(AGEs)from daily diets are thought to be a vital contributor to the development of this diseases.However,the effect of one of the best-characterized exogenous AGEs N^(ε)-(carboxymethyl)lysine(CML)on cognitive function is not fully reported.In the present study,diabetical Goto-Kakizaki(GK)rats were treated with free CML for 8-weeks.It was found that oral consumption of exogenous CML significantly aggravated diabetes-associated cognitive dysfunction in behavioral test.In details,exogenous CML increased levels of oxidative stress,promoted the activation of glial cells in the brain,up-regulated the release of inflammatory cytokines interleukin-6,inhibited the protein expression of the brain-derived neurotrophic factor and thus led to neuroinflammation.Furthermore,exogenous CML promoted the amyloidogenesis in the brain of GK rats,and inhibited the expression of GLUT4.Additionally,several tricarboxylic acid cycle and glutamate-glutamine/γ-aminobutyric acid cycle intermediates including pyruvate,succinic acid,glutamine,glutamate were significantly changed in brain of GK rats treated with exogenous free CML.In conclusion,exogenous free CML is a potentially noxious compounds led to aggravated diabetes-associated cognitive dysfunction which could be possibly explained by its effects on neuroinflammation,energy and neurotransmitter amino acid homeostasis.
基金supported by grants from the Ministerio de Economia y Competitividad(BFU2013-43458-R)Junta de Andalucia(P12-CTS-1694 and Proyexcel-00422)to ZUK。
文摘Memory deficit,which is often associated with aging and many psychiatric,neurological,and neurodegenerative diseases,has been a challenging issue for treatment.Up till now,all potential drug candidates have failed to produce satisfa ctory effects.Therefore,in the search for a solution,we found that a treatment with the gene corresponding to the RGS14414protein in visual area V2,a brain area connected with brain circuits of the ventral stream and the medial temporal lobe,which is crucial for object recognition memory(ORM),can induce enhancement of ORM.In this study,we demonstrated that the same treatment with RGS14414in visual area V2,which is relatively unaffected in neurodegenerative diseases such as Alzheimer s disease,produced longlasting enhancement of ORM in young animals and prevent ORM deficits in rodent models of aging and Alzheimer’s disease.Furthermore,we found that the prevention of memory deficits was mediated through the upregulation of neuronal arbo rization and spine density,as well as an increase in brain-derived neurotrophic factor(BDNF).A knockdown of BDNF gene in RGS14414-treated aging rats and Alzheimer s disease model mice caused complete loss in the upregulation of neuronal structural plasticity and in the prevention of ORM deficits.These findings suggest that BDNF-mediated neuronal structural plasticity in area V2 is crucial in the prevention of memory deficits in RGS14414-treated rodent models of aging and Alzheimer’s disease.Therefore,our findings of RGS14414gene-mediated activation of neuronal circuits in visual area V2 have therapeutic relevance in the treatment of memory deficits.
基金supported by Open Project of the Key Laboratory of Trauma and Orthopedics Research Medicine in Henan Province,No.HZKFKT20220504(to YZ)the National Natural Science Foundation of China,No.32000877(to YZ)and Open Scientific Research Program of Military Logistics,No.BLB20J009(to YZ)。
文摘Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-βdeposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive deficits.Furthermore,traumatic brain injury can exacerbate Alzheimer's disease-like pathologies,potentially leading to the development of Alzheimer's disease.Nanocarriers offer a potential solution by facilitating the delive ry of small interfering RNAs across the blood-brain barrier for the targeted silencing of key pathological genes implicated in traumatic brain injury and Alzheimer's disease.U nlike traditional approaches to neuro regeneration,this is a molecula r-targeted strategy,thus avoiding non-specific drug actions.This review focuses on the use of nanocarrier systems for the efficient and precise delive ry of siRNAs,discussing the advantages,challenges,and future directions.In principle,siRNAs have the potential to target all genes and non-targetable protein s,holding significant promise for treating various diseases.Among the various therapeutic approaches currently available for neurological diseases,siRNA gene silencing can precisely"turn off"the expression of any gene at the genetic level,thus radically inhibiting disease progression;however,a significant challenge lies in delivering siRNAs across the blood-brain barrier.Nanoparticles have received increasing attention as an innovative drug delive ry tool fo r the treatment of brain diseases.They are considered a potential therapeutic strategy with the advantages of being able to cross the blood-brain barrier,targeted drug delivery,enhanced drug stability,and multifunctional therapy.The use of nanoparticles to deliver specific modified siRNAs to the injured brain is gradually being recognized as a feasible and effective approach.Although this strategy is still in the preclinical exploration stage,it is expected to achieve clinical translation in the future,creating a new field of molecular targeted therapy and precision medicine for the treatment of Alzheimer's disease associated with traumatic brain injury.
基金supported by the Nature Science Foundation of Liaoning Province,Nos.2022-MS-211,2021-MS-064,and 2024-MS-048(all to YC).
文摘Alzheimer’s disease,a devastating neurodegenerative disorder,is characterized by progressive cognitive decline,primarily due to amyloid-beta protein deposition and tau protein phosphorylation.Effectively reducing the cytotoxicity of amyloid-beta42 aggregates and tau oligomers may help slow the progression of Alzheimer’s disease.Conventional drugs,such as donepezil,can only alleviate symptoms and are not able to prevent the underlying pathological processes or cognitive decline.Currently,active and passive immunotherapies targeting amyloid-beta and tau have shown some efficacy in mice with asymptomatic Alzheimer’s disease and other transgenic animal models,attracting considerable attention.However,the clinical application of these immunotherapies demonstrated only limited efficacy before the discovery of lecanemab and donanemab.This review first discusses the advancements in the pathogenesis of Alzheimer’s disease and active and passive immunotherapies targeting amyloid-beta and tau proteins.Furthermore,it reviews the advantages and disadvantages of various immunotherapies and considers their future prospects.Although some antibodies have shown promise in patients with mild Alzheimer’s disease,substantial clinical data are still lacking to validate their effectiveness in individuals with moderate Alzheimer’s disease.
基金Supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education,No.NRF-RS-2023-00237287.
文摘Sleep disorders,particularly insomnia,have emerged as a critical public health challenge,with the situation worsened by the coronavirus disease-2019 pandemic.Insomnia symptoms,which affected up to 45%of the population during this period,highlight the urgent need to understand the mechanisms linking sleep disturbances to mental health outcomes.Recent findings suggest that cognitive failures,such as memory lapses and attentional deficits,mediate the relationship between insomnia and emotional disorders such as anxiety and depression.The role of personality traits,particularly neuroticism,adds further complexity,as it may either exacerbate or buffer these effects under specific conditions.This review explores the study by Li et al,which offers valuable insights into the cognitive-emotional pathways influenced by sleep disturbances.The study makes significant contributions by identifying key cognitive mechanisms and proposing the dual role of neuroticism in shaping emotional outcomes.To advance these findings,this letter advocates for future longitudinal research and the integration of targeted interventions,such as cognitive-behavioral therapy for insomnia,into public health frameworks.By addressing insomnia-induced cognitive dysfunction,these strategies can enhance emotional regulation and foster resilience,particularly in vulnerable populations facing the mental health impacts of the pandemic.
基金Supported by the Top-Level Talents Support Program of Yangzhou University“Lv Yang Jin Feng”Outstanding Doctor of Yangzhou,No.YZLYJFJH2023YXBS169and Natural Science Foundation of Jiangsu Province,No.BK20240907。
文摘This article discusses a study by Li et al,which investigates the role of the microglial voltage-gated proton channel 1(Hv1)in diabetes-related cognitive decline.The authors showed that Hv1 is upregulated in the corpus callosum of diabetic mice and that its knockout improves working memory,reduces microglial production of interleukin-1βand tumour necrosis factor alpha,and decreases apoptosis of oligodendrocyte progenitor cells.Furthermore,electron microscopy revealed that the myelin thickness and the g-ratio were preserved in Hv1 knockout mice,remaining within normal limits.In addition,Hv1 knockdown mitigated interleukin-1βsecretion and suppressed ferroptosis markers(ferritin heavy chain/ferritin light chain,CCAAT/enhancer binding protein homologous protein,glucose-regulated protein 78,etc.)in vitro,suggesting the involvement of an Hv1-reactive oxygen species-glucose-regulated protein 78 axis in diabetic demyelination.We highlight the translational implications of these findings and recommend future studies employing microglia-specific Hv1 deletion models,longitudinal cognitive assessments and preclinical evaluation of pharmacological Hv1 inhibitors.
文摘Objective:To investigate whether nacre extract improves insulin sensitivity,brain glucose metabolism,and cognitive function in diabetic mice.Methods:Diabetic KK-Ay mice(n=5/group)were fed a standard diet or diets supplemented with nacre extract(125 or 250 mg/kg)for 13 weeks.Metabolic status was assessed by measuring fasting glucose and insulin levels,HOMA-IR,glucose tolerance,and insulin tolerance.The expression of IRS-1,IRS-2,and GLUT4 in the brain was analyzed by qPCR,Western blotting,and immunohistochemistry.Cognitive and anxiety-like behaviors were evaluated using the Y-maze,novel object recognition,Barnes maze,and open field tests.Results:Nacre extract significantly reduced fasting glucose and insulin levels,improved HOMA-IR,and enhanced glucose and insulin tolerance(P<0.05)in diabetic mice.It also restored GLUT4 expression and significantly upregulated SIRT1 and BDNF.Behavioral assessments showed significant improvements in memory and reduced anxiety-like behaviors.Conclusions:Nacre extract enhances insulin sensitivity,improves brain glucose metabolism,and alleviates cognitive and emotional dysfunction in diabetic mice.Further studies are warranted to verify the exact molecular mechanisms and efficacy of nacre extract in diabetes-associated metabolic and neurocognitive dysfunction.
基金Supported by National Natural Science Foundation of China:Role and Mechanism of Microglial Environmental Sensing Element P2RY13 in Ischemic Brain Injury (No.81920108017)Key Research and Development Program of Jiangsu Province of China:Research on the Early Diagnosis, Treatment and Evaluation System and Early Warning Model of Ischemic Cerebrovascular Disease (No.BE2020620)
文摘OBJECTIVE:To explore the effect of Traditional Chinese Medicine(TCM)constitution on cognitive impairment(CI)in patients with cerebral small vessel disease(CSVD)and its underlying neuroimaging mechanism and to provide countermeasures for health management of CSVD patients.METHODS:A total of 241 CSVD patients were recruited from the Department of Neurology.All subjects underwent head magnetic resonance imaging(MRI),Chinese Medicine Questionnaire(CCMQ)and cognitive function examination.The CSVD patients were divided according to the Montreal Cognitive Assessment(MoCA)score into a normal cognitive group(73 cases)and a CI group(168 cases).Logistic regression was used to analyse the risk constitution of CSVD-CI and to construct a risk prediction model.3DT1 MRI images and FreeSurfer 6.0 software(Athinoula A.Martinos,Boston,MA,USA)were used to further explore the involvement of hippocampal subregion volume in patients with at-risk constitution and its correlation with cognitive function.RESULTS:Logistic regression analysis showed that Yang-deficiency constitution(YADC)(P=0.020),older age(P=0.008)and hypertension(P=0.011)were risk factors for CSVD-CI but that balanced constitution(P=0.003)and education(P<0.001)were protective factors.A receiver operating characteristic curve(ROC)was drawn,and the area under the curve was 0.820.Further comparison of overall hippocampal and 12 hippocampal subregion volumes between YADC and non-YADC patients revealed decreased total volume of the left and right hippocampus,bilateral subiculum,presubiculum,molecular layer and right fimbria in the YADC group(P<0.05/13,13 is the number of hypothesis tests).Moreover,in the YADC group,the cognitive function of CSVD patients correlated positively with the overall volume of the left hippocampus(r=0.304,P<0.05)and the molecular layer volume of the left hippocampus(r=0.288,P<0.05).CONCLUSION:CSVD patients with YADC are more prone towards developing CI,and asymmetric atrophy of the hippocampus might be the underlying neuroimaging mechanism.In particular,the volume of the left whole hippocampus and the left hippocampal molecular layer correlated significantly with general cognitive function.
基金supported by the National Natural Science Foundation of China,Nos. 82173806 and U1803281Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science,Nos. 2021-I2M-1-030 and 2022-I2M-2-002Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences,No. 2022-JKCS-08 (all to RL)。
文摘Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The long noncoding RNA growth arrest-specific 5(GAS5) is a member of the 5′-terminal oligopyrimidine gene family that may be involved in neurological disorders, but its role in Alzheimer's disease remains unclear. This study aimed to investigate the function of GAS5 and construct a GAS5-associated competitive endogenous RNA network comprising potential targets. RNA sequencing results showed that GAS5 was upregulated in five familial Alzheimer's disease(5×FAD) mice, APPswe/PSEN1dE9(APP/PS1) mice, Alzheimer's disease-related APPswe cells, and serum from patients with Alzheimer's disease. Functional experiments with targeted overexpression and silencing demonstrated that GAS5 played a role in cognitive dysfunction and multiple Alzheimer's disease-associated pathologies, including tau hyperphosphorylation, amyloid-beta accumulation, and neuronal apoptosis. Mechanistic studies indicated that GAS5 acted as an endogenous sponge by competing for microRNA-23b-3p(miR-23b-3p) binding to regulate its targets glycogen synthase kinase 3beta(GSK-3β) and phosphatase and tensin homologue deleted on chromosome 10(PTEN) expression in an Argonaute 2-induced RNA silencing complex(RISC)-dependent manner. GAS5 inhibited miR-23b-3p-mediated GSK-3β and PTEN cascades with a feedforward PTEN/protein kinase B(Akt)/GSK-3β linkage. Furthermore, recovery of GAS5/miR-23b-3p/GSK-3β/PTEN pathways relieved Alzheimer's disease-like symptoms in vivo, indicated by the amelioration of spatial cognition, neuronal degeneration, amyloid-beta load, and tau phosphorylation. Together, these findings suggest that GAS5 promotes Alzheimer's disease pathogenesis. This study establishes the functional convergence of the GAS5/miR-23b-3p/GSK-3β/PTEN pathway on multiple pathologies, suggesting a candidate therapeutic target in Alzheimer's disease.
基金supported by 2023 Jiangsu Xuzhou Medical Higher Vocational School Natural Science Project(No.2023ZZX09)。
文摘Objective:Investigating the effects and molecular mechanisms of nursing interventions based on environmental enrichment on cognitive function in ischemic stroke rats.Methods:A total of 30 Sprague-Dawley(SD)rats belonging to the same batch were randomly divided into 3 groups(n=10)using a random number table:Sham Surgery Control Group(Sham),Ischemia-Reperfusion(I/R)Group,and Ischemia-Reperfusion Group with Environmental Enrichment Intervention(I/R+EEI).The expression levels of brain-derived neurotrophic factor(BDNF)protein in the hippocampus region were measured and compared among different groups.Results:Compared with the Sham group,the I/R group showed significantly reduced learning and memory abilities,with notably lower BDNF levels(P<0.05).Compared to the I/R group,the I/R+EEI group exhibited significantly improved learning and memory abilities as well as increased BDNF protein levels(P<0.05).Conclusions:Abnormal BDNF protein secretion may be the molecular mechanism of cognitive dysfunction due to hippocampal neuronal damage in ischemia-reperfusion,and modifying this neurotransmitter’s secretion can effectively improve cognitive function in ischemia-reperfusion rats.
