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
Inflammation may play a role in postoperative cognitive dysfunction. 5＇ Adenosine monophos- phate-activated protein kinase, nuclear factor-kappa B, interleukin-1β, and tumor necrosis factor-a are involved in inflamm...Inflammation may play a role in postoperative cognitive dysfunction. 5＇ Adenosine monophos- phate-activated protein kinase, nuclear factor-kappa B, interleukin-1β, and tumor necrosis factor-a are involved in inflammation. Therefore, these inflammatory mediators may be involved in postoperative cognitive dysfunction. Western immunoblot analysis revealed 5＇ adenosine mo- nophosphate-activated protein kinase and nuclear factor-kappa B in the hippocampus of aged rats were increased 1-7 days after splenectomy. Moreover, interleukin-1β and tumor necrosis fac- tor-α were upregulated and gradually decreased. Therefore, these inflammatory mediators may participate in the splenectomy model of postoperative cognitive dysfunction in aged rats.展开更多
The causal mechanisms and treatment for the negative symptoms and cognitive dysfunction in schizophrenia are the main issues attracting the attention of psychiatrists over the last decade.The first part of this review...The causal mechanisms and treatment for the negative symptoms and cognitive dysfunction in schizophrenia are the main issues attracting the attention of psychiatrists over the last decade.The first part of this review summarizes the pathogenesis of schizophrenia,especially the negative symptoms and cognitive dysfunction from the perspectives of genetics and epigenetics.The second part describes the novel medications and several advanced physical therapies(e.g.,transcranial magnetic stimulation and transcranial direct current stimulation)for the negative symptoms and cognitive dysfunction that will optimize the therapeutic strategy for patients with schizophrenia in future.展开更多
This study established an aged rat model of cognitive dysfunction using anesthesia with 2% iso- flurane and 80% oxygen for 2 hours. Twenty-four hours later, Y-maze test results showed that isoflurane significantly imp...This study established an aged rat model of cognitive dysfunction using anesthesia with 2% iso- flurane and 80% oxygen for 2 hours. Twenty-four hours later, Y-maze test results showed that isoflurane significantly impaired cognitive function in aged rats. Gas chromatography-mass spectrometry results showed that isoflurane also significantly increased the levels of N,N-diethy- lacetamide, n-ethylacetamide, aspartic acid, malic acid and arabinonic acid in the hippocampus of isoflurane-treated rats. Moreover, aspartic acid, N,N-diethylacetamide, n-ethylacetamide and malic acid concentration was positively correlated with the degree of cognitive dysfunction in the isoflurane-treated rats. It is evident that hippocampal metabolite changes are involved in the formation of cognitive dysfunction after isoflurane anesthesia. To further verify these results, this study cultured hippocampal neurons in vitro, which were then treated with aspartic acid （100 μmol/L）. Results suggested that aspartic acid concentration in the hippocampus may be a biomarker for predicting the occurrence and disease progress of cognitive dysfunction.展开更多
Objective： To explore the relationship of postoperative cognitive dysfunction （POCD） in one-lung ventilation （OLV） patients and regional cerebral oxygen saturation （rSO2）. Methods： Twenty-nine male and twenty-...Objective： To explore the relationship of postoperative cognitive dysfunction （POCD） in one-lung ventilation （OLV） patients and regional cerebral oxygen saturation （rSO2）. Methods： Twenty-nine male and twenty-one female cases of OLV received thoracic surgery, with American Standards Association （ASA） physical status being at Grades Ⅰ-Ⅲ. Neuropsychological tests were performed on the day before operation and 7 d after operation, and there was an intraoperative continuous monitoring of rSO2. The values of rSO2 before anesthesia induction （t1）, at the beginning of OLV （t2）, and at the time of OLV 30 min （t3）, OLV 60 min （t4）, the end of OLV （t5）, and the end of surgery （t6） were recorded. The intraoperative average of rSO2 （ rSO2 ）, the intraoperative minimum value of rSO2 （rSO2, rn=n）, and the reduced maximum percentage of rSO2 （rSO2, %max） when compared with the baseline value were calculated. The volume of blood loss, urine output, and the amount of fluid infusion was recorded. Results： A total of 14 patients （28%） in the 50 cases suffered from POCD. The values of mini-mental state examination （MMSE）, the digit span and the digit symbol on the 7th day after the operation for POCD in OLV patients were found to be significantly lower than those before the operation （P〈0.05）. The values of MMSE and vocabulary fluency scores were significantly lower than those in the non-POCD group （P〈0.05）. The values of rSO2 in the POCD group of OLV patients at t2 and t3 and the values of rSO2 in the non-POCD group at t2 were found to be significantly higher than those at tl （P〈0.05）. The values of rSO2, %max in the POCD group were significantly higher than those in the non-POCD group （P〈0.05）. When the value of rSO2, %max is more than 10.1%, it may act as an early warning index for cognitive function changes, Conclusions： POCD after OLV may be associated with a decline in rSO2.展开更多
Occupational exposure to 1-bromopropane(1-BP) induces learning and memory deficits. However, no therapeutic strategies are currently available. Accumulating evidence has suggested that N-methyl-D-aspartate receptors(N...Occupational exposure to 1-bromopropane(1-BP) induces learning and memory deficits. However, no therapeutic strategies are currently available. Accumulating evidence has suggested that N-methyl-D-aspartate receptors(NMDARs) and neuroinflammation are involved in the cognitive impairments in neurodegenerative diseases. In this study we aimed to investigate whether the noncompetitive NMDAR antagonist MK801 protects against 1-BPinduced cognitive dysfunction. Male Wistar rats were administered with MK801(0.1 mg/kg) prior to 1-BP intoxication(800 mg/kg). Their cognitive performance was evaluated by the Morris water maze test. The brains of rats were dissected for biochemical, neuropathological,and immunological analyses. We found that the spatial learning and memory were significantly impaired in the1-BP group, and this was associated with neurodegeneration in both the hippocampus(especially CA1 and CA3)and cortex. Besides, the protein levels of phosphorylated NMDARs were increased after 1-BP exposure. MK801 ameliorated the 1-BP-induced cognitive impairments and degeneration of neurons in the hippocampus and cortex.Mechanistically, MK801 abrogated the 1-BP-induced disruption of excitatory and inhibitory amino-acid balance and NMDAR abnormalities. Subsequently, MK801 inhibited the microglial activation and release of pro-inflammatory cytokines in 1-BP-treated rats. Our findings, for the first time, revealed that MK801 protected against 1-BP-induced cognitive dysfunction by ameliorating NMDAR function and blocking microglial activation, which might provide a potential target for the treatment of 1-BP poisoning.展开更多
Postoperative cognitive dysfunction(POCD)is a common surgical complication.Diabetes mellitus(DM)increases risk of developing POCD after surgery.DM patients with POCD seriously threaten the quality of patients’life,ho...Postoperative cognitive dysfunction(POCD)is a common surgical complication.Diabetes mellitus(DM)increases risk of developing POCD after surgery.DM patients with POCD seriously threaten the quality of patients’life,however,the intrinsic mechanism is unclear,and the effective treatment is deficiency.Previous studies have demonstrated neuronal loss and reduced neurogenesis in the hippocampus in mouse models of POCD.In this study,we constructed a mouse model of DM by intraperitoneal injection of streptozotocin,and then induced postoperative cognitive dysfunction by transient bilateral common carotid artery occlusion.We found that mouse models of DM-POCD exhibited the most serious cognitive impairment,as well as the most hippocampal neural stem cells(H-NSCs)loss and neurogenesis decline.Subsequently,we hypothesized that small extracellular vesicles secreted by induced pluripotent stem cell-derived mesenchymal stem cells(iMSC-sEVs)might promote neurogenesis and restore cognitive function in patients with DM-POCD.iMSC-sEVs were administered via the tail vein beginning on day 2 after surgery,and then once every 3 days for 1 month thereafter.Our results showed that iMSC-sEVs treatment significantly recovered compromised proliferation and neuronal-differentiation capacity in H-NSCs,and reversed cognitive impairment in mouse models of DM-POCD.Furthermore,miRNA sequencing and qPCR showed miR-21-5p and miR-486-5p were the highest expression in iMSC-sEVs.We found iMSC-sEVs mainly transferred miR-21-5p and miR-486-5p to promote H-NSCs proliferation and neurogenesis.As miR-21-5p was demonstrated to directly targete Epha4 and CDKN2C,while miR-486-5p can inhibit FoxO1 in NSCs.We then demonstrated iMSC-sEVs can transfer miR-21-5p and miR-486-5p to inhibit EphA4,CDKN2C,and FoxO1 expression in H-NSCs.Collectively,these results indicate significant H-NSC loss and neurogenesis reduction lead to DM-POCD,the application of iMSC-sEVs may represent a novel cell-free therapeutic tool for diabetic patients with postoperative cognitive dysfunction.展开更多
Objective： To investigate the relationship between post-operative cognitive dysfunction（POCD） and regional cerebral oxygen saturation（rSO2） and β-amyloid protein（Aβ） in patients undergoing laparoscopic pancre...Objective： To investigate the relationship between post-operative cognitive dysfunction（POCD） and regional cerebral oxygen saturation（rSO2） and β-amyloid protein（Aβ） in patients undergoing laparoscopic pancreaticoduodenectomy. Methods： Fifty patients undergoing elective laparoscopic pancreaticoduodenectomy received five groups of neuropsychological tests 1 d pre-operatively and 7 d post-operatively, with continuous monitoring of rSO2 intra-operatively. Before anesthesia induction（t0）, at the beginning of laparoscopy（t1）, and at the time of pneumoperitoneum 120 min（t2）, pneumoperitoneum 240 min（t3）, pneumoperitoneum 480 min（t4）, the end of pneumoperitoneum（t5）, and 24 h after surgery, jugular venous blood was drawn respectively for the measurement of Aβ by enzyme-linked immunosorbent assay（ELISA）. Results： Twenty-one cases of the fifty patients suffered from POCD after operation. We found that the maximum percentage drop in rSO2（rSO2, %max） was significantly higher in the POCD group than in the non-POCD group. The rSO2, %max value of over 10.2% might be a potential predictor of neurocognitive injury for those patients. In the POCD group, the plasma Aβ levels after 24 h were significantly higher than those of pre-operative values（P〈0.01）. After 24 h, levels of plasma Aβ in the POCD group were significantly higher than those in the non-POCD group（P〈0.01）. Conclusions： The development of POCD in patients undergoing laparoscopic pancreaticoduodenectomy is associated with alterations of rSO2 and Aβ. Monitoring of rSO2 might be useful in the prediction of POCD, and Aβ might be used as a sensitive biochemical marker to predict the occurrence of POCD.展开更多
BACKGROUND Type 2 diabetes mellitus(T2DM) has been strongly associated with an increased risk of developing cognitive dysfunction and dementia.The mechanisms of diabetes-associated cognitive dysfunction(DACD) have not...BACKGROUND Type 2 diabetes mellitus(T2DM) has been strongly associated with an increased risk of developing cognitive dysfunction and dementia.The mechanisms of diabetes-associated cognitive dysfunction(DACD) have not been fully elucidated to date.Some studies proved lower cerebral blood flow(CBF) in the hippocampus was associated with poor executive function and memory in T2DM.Increasing evidence showed that diabetes leads to abnormal vascular endothelial growth factor(VEGF) expression and CBF changes in humans and animal models.In this study,we hypothesized that DACD was correlated with CBF alteration as measured by three-dimensional(3D) arterial spin labeling(3D-ASL) and VEGF expression in the hippocampus.AIM To assess the correlation between CBF(measured by 3D-ASL and VEGF expression) and DACD in a rat model of T2DM.METHODS Forty Sprague-Dawley male rats were divided into control and T2DM groups.The T2DM group was established by feeding rats a high-fat diet and glucose to induce impaired glucose tolerance and then injecting them with streptozotocin to induce T2DM.Cognitive function was assessed using the Morris water maze experiment.The CBF changes were measured by 3D-ASL magnetic resonance imaging.VEGF expression was determined using immunofluorescence.RESULTS The escape latency time significantly reduced 15 wk after streptozotocin injection in the T2DM group.The total distance traveled was longer in the T2DM group;also,the platform was crossed fewer times.The percentage of distance in the target zone significantly decreased.CBF decreased in the bilateral hippocampus in the T2DM group.No difference was found between the right CBF value and the left CBF value in the T2DM group.The VEGF expression level in the hippocampus was lower in the T2DM group and correlated with the CBF value.The escape latency negatively correlated with the CBF value.The number of rats crossing the platform positively correlated with the CBF value.CONCLUSION Low CBF in the hippocampus and decreased VEGF expression might be crucial in DACD.CBF measured by 3D-ASL might serve as a noninvasive imaging biomarker for cognitive impairment associated with T2DM.展开更多
The incidence of diabetes is gradually increasing in China,and diabetes and associated complications,such as cognitive dysfunction have gained much attention in recent time.However,the concepts,clinical treatment,and ...The incidence of diabetes is gradually increasing in China,and diabetes and associated complications,such as cognitive dysfunction have gained much attention in recent time.However,the concepts,clinical treatment,and prevention of cognitive dysfunction in patients with diabetes remain unclear.The Chinese Society of Endocrinology investigated the current national and overseas situation of cognitive dysfunction associated with diabetes.Based on research both in China and other countries worldwide,the Expert Consensus on Cognitive Dysfunction in Diabetes was established to guide physicians in the comprehensive standardized management of cognitive dysfunction in diabetes and to improve clinical outcomes in Chinese patients.This consensus presents an overview,definition and classification,epidemiology and pathogenesis,risk factors,screening,diagnosis,differential diagnosis,treatment,and prevention of cognitive dysfunction in patients with diabetes.展开更多
Objective Post-operative cognitive dysfunction(POCD)and post-operative delirium(POD)are two common post-operative cerebral complications.The current meta-analysis was to systematically review the effects of penehyclid...Objective Post-operative cognitive dysfunction(POCD)and post-operative delirium(POD)are two common post-operative cerebral complications.The current meta-analysis was to systematically review the effects of penehyclidine hydrochloride(PHC)on POCD and POD in surgical patients.Methods Electronic databases were searched to identify all randomized controlled trials comparing PHC with atropine/scopolamine/placebo on POCD and POD in surgical patients.Primary outcomes of interest included the incidences of POCD and POD;the secondary outcomes of interest included peri-operative minimental state examination(MMSE)scores.Two authors independently extracted peri-operative data,including patients'baseline characteristics,surgical variables,and outcome data.For dichotomous data(POCD and POD occurrence),treatment effects were calculated as odds ratio(OR)and 95%confidential interval(Cl).Each outcome was tested for heterogeneity,and randomized-effects or fixed-effects model was used in the presence or absence of significant heterogeneity.For continuous variables(MMSE scores),treatment effects were calculated as weighted mean difference(WMD)and 95%CI.Statistical significance was defined as P<0.05.Results Our search yielded 33 studies including 4017 patients.Meta-analysis showed that,the incidence of POCD in PHC group was comparable to that in saline group(OR=0.97;95%Ck 0.S8-1.64;P=0.92),scopolamine group(OR=0.78;95%CI:0.48-1.27;P=0.32)and atropine group(0R=1.20;95%Ch 0.86-1.67;P=0.29).The incidence of POD in PHC group was comparable to that in saline group(OR=1.53;95%CI:0.81-2.90;P=0.19)and scopolamine group(OR=0.53;95%CI:0.06-4.56;P=0.56),but higher than that in atropine group(OR=4.49;95%CI:1.34-15.01;P=0.01).Conclusions PHC premedication was not associated with increased incidences of POCD or POD as compared to either scopolamine or placebo.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.
文摘Inflammation may play a role in postoperative cognitive dysfunction. 5＇ Adenosine monophos- phate-activated protein kinase, nuclear factor-kappa B, interleukin-1β, and tumor necrosis factor-a are involved in inflammation. Therefore, these inflammatory mediators may be involved in postoperative cognitive dysfunction. Western immunoblot analysis revealed 5＇ adenosine mo- nophosphate-activated protein kinase and nuclear factor-kappa B in the hippocampus of aged rats were increased 1-7 days after splenectomy. Moreover, interleukin-1β and tumor necrosis fac- tor-α were upregulated and gradually decreased. Therefore, these inflammatory mediators may participate in the splenectomy model of postoperative cognitive dysfunction in aged rats.
基金This review was supported by the National Key R&D Program of China(2016YFC1306900)the National Natural Science Foundation of China(81622018)an Innovation Driven Project of Central South University(2020CX018).
文摘The causal mechanisms and treatment for the negative symptoms and cognitive dysfunction in schizophrenia are the main issues attracting the attention of psychiatrists over the last decade.The first part of this review summarizes the pathogenesis of schizophrenia,especially the negative symptoms and cognitive dysfunction from the perspectives of genetics and epigenetics.The second part describes the novel medications and several advanced physical therapies(e.g.,transcranial magnetic stimulation and transcranial direct current stimulation)for the negative symptoms and cognitive dysfunction that will optimize the therapeutic strategy for patients with schizophrenia in future.
基金supported by the National Natural Science Foundation of China,No.30871306
文摘This study established an aged rat model of cognitive dysfunction using anesthesia with 2% iso- flurane and 80% oxygen for 2 hours. Twenty-four hours later, Y-maze test results showed that isoflurane significantly impaired cognitive function in aged rats. Gas chromatography-mass spectrometry results showed that isoflurane also significantly increased the levels of N,N-diethy- lacetamide, n-ethylacetamide, aspartic acid, malic acid and arabinonic acid in the hippocampus of isoflurane-treated rats. Moreover, aspartic acid, N,N-diethylacetamide, n-ethylacetamide and malic acid concentration was positively correlated with the degree of cognitive dysfunction in the isoflurane-treated rats. It is evident that hippocampal metabolite changes are involved in the formation of cognitive dysfunction after isoflurane anesthesia. To further verify these results, this study cultured hippocampal neurons in vitro, which were then treated with aspartic acid （100 μmol/L）. Results suggested that aspartic acid concentration in the hippocampus may be a biomarker for predicting the occurrence and disease progress of cognitive dysfunction.
基金supported by the Foundation of Shandong Science and Technology Project(No.2011YD18070),China
文摘Objective： To explore the relationship of postoperative cognitive dysfunction （POCD） in one-lung ventilation （OLV） patients and regional cerebral oxygen saturation （rSO2）. Methods： Twenty-nine male and twenty-one female cases of OLV received thoracic surgery, with American Standards Association （ASA） physical status being at Grades Ⅰ-Ⅲ. Neuropsychological tests were performed on the day before operation and 7 d after operation, and there was an intraoperative continuous monitoring of rSO2. The values of rSO2 before anesthesia induction （t1）, at the beginning of OLV （t2）, and at the time of OLV 30 min （t3）, OLV 60 min （t4）, the end of OLV （t5）, and the end of surgery （t6） were recorded. The intraoperative average of rSO2 （ rSO2 ）, the intraoperative minimum value of rSO2 （rSO2, rn=n）, and the reduced maximum percentage of rSO2 （rSO2, %max） when compared with the baseline value were calculated. The volume of blood loss, urine output, and the amount of fluid infusion was recorded. Results： A total of 14 patients （28%） in the 50 cases suffered from POCD. The values of mini-mental state examination （MMSE）, the digit span and the digit symbol on the 7th day after the operation for POCD in OLV patients were found to be significantly lower than those before the operation （P〈0.05）. The values of MMSE and vocabulary fluency scores were significantly lower than those in the non-POCD group （P〈0.05）. The values of rSO2 in the POCD group of OLV patients at t2 and t3 and the values of rSO2 in the non-POCD group at t2 were found to be significantly higher than those at tl （P〈0.05）. The values of rSO2, %max in the POCD group were significantly higher than those in the non-POCD group （P〈0.05）. When the value of rSO2, %max is more than 10.1%, it may act as an early warning index for cognitive function changes, Conclusions： POCD after OLV may be associated with a decline in rSO2.
基金supported by the National Natural Science Foundation of China(81872654,81703264)Fundamental Research Funds of Shandong University(2016JC020),ChinaNatural Science Foundation of Shandong Province(ZR2017MH002),China
文摘Occupational exposure to 1-bromopropane(1-BP) induces learning and memory deficits. However, no therapeutic strategies are currently available. Accumulating evidence has suggested that N-methyl-D-aspartate receptors(NMDARs) and neuroinflammation are involved in the cognitive impairments in neurodegenerative diseases. In this study we aimed to investigate whether the noncompetitive NMDAR antagonist MK801 protects against 1-BPinduced cognitive dysfunction. Male Wistar rats were administered with MK801(0.1 mg/kg) prior to 1-BP intoxication(800 mg/kg). Their cognitive performance was evaluated by the Morris water maze test. The brains of rats were dissected for biochemical, neuropathological,and immunological analyses. We found that the spatial learning and memory were significantly impaired in the1-BP group, and this was associated with neurodegeneration in both the hippocampus(especially CA1 and CA3)and cortex. Besides, the protein levels of phosphorylated NMDARs were increased after 1-BP exposure. MK801 ameliorated the 1-BP-induced cognitive impairments and degeneration of neurons in the hippocampus and cortex.Mechanistically, MK801 abrogated the 1-BP-induced disruption of excitatory and inhibitory amino-acid balance and NMDAR abnormalities. Subsequently, MK801 inhibited the microglial activation and release of pro-inflammatory cytokines in 1-BP-treated rats. Our findings, for the first time, revealed that MK801 protected against 1-BP-induced cognitive dysfunction by ameliorating NMDAR function and blocking microglial activation, which might provide a potential target for the treatment of 1-BP poisoning.
基金supported by the National Natural Science Foundation of China,No.82101463(to GWH)Natural Science Foundation of Jiangxi Provincial Science and Technology Department,No.20202BAB216013(to HLL)+1 种基金Jiangxi Provincial Health Commission General Science and Technology Project,No.202130370(to HLL)The Second Affiliated Hospital of Nanchang University’s Youth Innovation Team of Science and Technology Program,No.2019YNQN12009(to HLL)。
文摘Postoperative cognitive dysfunction(POCD)is a common surgical complication.Diabetes mellitus(DM)increases risk of developing POCD after surgery.DM patients with POCD seriously threaten the quality of patients’life,however,the intrinsic mechanism is unclear,and the effective treatment is deficiency.Previous studies have demonstrated neuronal loss and reduced neurogenesis in the hippocampus in mouse models of POCD.In this study,we constructed a mouse model of DM by intraperitoneal injection of streptozotocin,and then induced postoperative cognitive dysfunction by transient bilateral common carotid artery occlusion.We found that mouse models of DM-POCD exhibited the most serious cognitive impairment,as well as the most hippocampal neural stem cells(H-NSCs)loss and neurogenesis decline.Subsequently,we hypothesized that small extracellular vesicles secreted by induced pluripotent stem cell-derived mesenchymal stem cells(iMSC-sEVs)might promote neurogenesis and restore cognitive function in patients with DM-POCD.iMSC-sEVs were administered via the tail vein beginning on day 2 after surgery,and then once every 3 days for 1 month thereafter.Our results showed that iMSC-sEVs treatment significantly recovered compromised proliferation and neuronal-differentiation capacity in H-NSCs,and reversed cognitive impairment in mouse models of DM-POCD.Furthermore,miRNA sequencing and qPCR showed miR-21-5p and miR-486-5p were the highest expression in iMSC-sEVs.We found iMSC-sEVs mainly transferred miR-21-5p and miR-486-5p to promote H-NSCs proliferation and neurogenesis.As miR-21-5p was demonstrated to directly targete Epha4 and CDKN2C,while miR-486-5p can inhibit FoxO1 in NSCs.We then demonstrated iMSC-sEVs can transfer miR-21-5p and miR-486-5p to inhibit EphA4,CDKN2C,and FoxO1 expression in H-NSCs.Collectively,these results indicate significant H-NSC loss and neurogenesis reduction lead to DM-POCD,the application of iMSC-sEVs may represent a novel cell-free therapeutic tool for diabetic patients with postoperative cognitive dysfunction.
基金Project supported by the Shandong Science and Technology Development Project(No.2011YD18070),China
文摘Objective： To investigate the relationship between post-operative cognitive dysfunction（POCD） and regional cerebral oxygen saturation（rSO2） and β-amyloid protein（Aβ） in patients undergoing laparoscopic pancreaticoduodenectomy. Methods： Fifty patients undergoing elective laparoscopic pancreaticoduodenectomy received five groups of neuropsychological tests 1 d pre-operatively and 7 d post-operatively, with continuous monitoring of rSO2 intra-operatively. Before anesthesia induction（t0）, at the beginning of laparoscopy（t1）, and at the time of pneumoperitoneum 120 min（t2）, pneumoperitoneum 240 min（t3）, pneumoperitoneum 480 min（t4）, the end of pneumoperitoneum（t5）, and 24 h after surgery, jugular venous blood was drawn respectively for the measurement of Aβ by enzyme-linked immunosorbent assay（ELISA）. Results： Twenty-one cases of the fifty patients suffered from POCD after operation. We found that the maximum percentage drop in rSO2（rSO2, %max） was significantly higher in the POCD group than in the non-POCD group. The rSO2, %max value of over 10.2% might be a potential predictor of neurocognitive injury for those patients. In the POCD group, the plasma Aβ levels after 24 h were significantly higher than those of pre-operative values（P〈0.01）. After 24 h, levels of plasma Aβ in the POCD group were significantly higher than those in the non-POCD group（P〈0.01）. Conclusions： The development of POCD in patients undergoing laparoscopic pancreaticoduodenectomy is associated with alterations of rSO2 and Aβ. Monitoring of rSO2 might be useful in the prediction of POCD, and Aβ might be used as a sensitive biochemical marker to predict the occurrence of POCD.
基金Supported by The Endocrine Clinical Medical Center of Yunnan ProvinceNo.ZX20190202+2 种基金the Fund of the Diabetic Innovation Team in Yunnan Province,No.2019HC002the Special Joint Fund from Yunnan Provincial Department of Science and Technology and Kunming Medical University,Kunming,Yunnan,China,No.2018FE001(-267)the SKY Image Research Fund,China,No. Z-2014-07-2003-12。
文摘BACKGROUND Type 2 diabetes mellitus(T2DM) has been strongly associated with an increased risk of developing cognitive dysfunction and dementia.The mechanisms of diabetes-associated cognitive dysfunction(DACD) have not been fully elucidated to date.Some studies proved lower cerebral blood flow(CBF) in the hippocampus was associated with poor executive function and memory in T2DM.Increasing evidence showed that diabetes leads to abnormal vascular endothelial growth factor(VEGF) expression and CBF changes in humans and animal models.In this study,we hypothesized that DACD was correlated with CBF alteration as measured by three-dimensional(3D) arterial spin labeling(3D-ASL) and VEGF expression in the hippocampus.AIM To assess the correlation between CBF(measured by 3D-ASL and VEGF expression) and DACD in a rat model of T2DM.METHODS Forty Sprague-Dawley male rats were divided into control and T2DM groups.The T2DM group was established by feeding rats a high-fat diet and glucose to induce impaired glucose tolerance and then injecting them with streptozotocin to induce T2DM.Cognitive function was assessed using the Morris water maze experiment.The CBF changes were measured by 3D-ASL magnetic resonance imaging.VEGF expression was determined using immunofluorescence.RESULTS The escape latency time significantly reduced 15 wk after streptozotocin injection in the T2DM group.The total distance traveled was longer in the T2DM group;also,the platform was crossed fewer times.The percentage of distance in the target zone significantly decreased.CBF decreased in the bilateral hippocampus in the T2DM group.No difference was found between the right CBF value and the left CBF value in the T2DM group.The VEGF expression level in the hippocampus was lower in the T2DM group and correlated with the CBF value.The escape latency negatively correlated with the CBF value.The number of rats crossing the platform positively correlated with the CBF value.CONCLUSION Low CBF in the hippocampus and decreased VEGF expression might be crucial in DACD.CBF measured by 3D-ASL might serve as a noninvasive imaging biomarker for cognitive impairment associated with T2DM.
文摘The incidence of diabetes is gradually increasing in China,and diabetes and associated complications,such as cognitive dysfunction have gained much attention in recent time.However,the concepts,clinical treatment,and prevention of cognitive dysfunction in patients with diabetes remain unclear.The Chinese Society of Endocrinology investigated the current national and overseas situation of cognitive dysfunction associated with diabetes.Based on research both in China and other countries worldwide,the Expert Consensus on Cognitive Dysfunction in Diabetes was established to guide physicians in the comprehensive standardized management of cognitive dysfunction in diabetes and to improve clinical outcomes in Chinese patients.This consensus presents an overview,definition and classification,epidemiology and pathogenesis,risk factors,screening,diagnosis,differential diagnosis,treatment,and prevention of cognitive dysfunction in patients with diabetes.
文摘Objective Post-operative cognitive dysfunction(POCD)and post-operative delirium(POD)are two common post-operative cerebral complications.The current meta-analysis was to systematically review the effects of penehyclidine hydrochloride(PHC)on POCD and POD in surgical patients.Methods Electronic databases were searched to identify all randomized controlled trials comparing PHC with atropine/scopolamine/placebo on POCD and POD in surgical patients.Primary outcomes of interest included the incidences of POCD and POD;the secondary outcomes of interest included peri-operative minimental state examination(MMSE)scores.Two authors independently extracted peri-operative data,including patients'baseline characteristics,surgical variables,and outcome data.For dichotomous data(POCD and POD occurrence),treatment effects were calculated as odds ratio(OR)and 95%confidential interval(Cl).Each outcome was tested for heterogeneity,and randomized-effects or fixed-effects model was used in the presence or absence of significant heterogeneity.For continuous variables(MMSE scores),treatment effects were calculated as weighted mean difference(WMD)and 95%CI.Statistical significance was defined as P<0.05.Results Our search yielded 33 studies including 4017 patients.Meta-analysis showed that,the incidence of POCD in PHC group was comparable to that in saline group(OR=0.97;95%Ck 0.S8-1.64;P=0.92),scopolamine group(OR=0.78;95%CI:0.48-1.27;P=0.32)and atropine group(0R=1.20;95%Ch 0.86-1.67;P=0.29).The incidence of POD in PHC group was comparable to that in saline group(OR=1.53;95%CI:0.81-2.90;P=0.19)and scopolamine group(OR=0.53;95%CI:0.06-4.56;P=0.56),but higher than that in atropine group(OR=4.49;95%CI:1.34-15.01;P=0.01).Conclusions PHC premedication was not associated with increased incidences of POCD or POD as compared to either scopolamine or placebo.
