Postoperative programming is an important part of deep brain stimulation (DBS) for patients with Parkinson's disease (PD). Standardized postoperative programming can clarify the best stimulation parameters, relieve the symptoms of patients, and improve the quality of life of PD patients. Remote programming connects DBS device through the Internet and adjusts the parameters remotely. At present, the development of remote programming in China is still limited to relatively large DBS centers, without wide application. Standardized management advice for remote programming is needed so that more patients can benefit from it. Based on this, relevant experts summarized the latest research results of PD-DBS and postoperative remote programming in recent years; by combining with the clinical experiences of the expert group, the "Chinese expert consensus on remote programming after DBS for Parkinson's disease" is generated.
Purpose: The aim of this study was to explore the correlation between brain functional network alterations and cerebrospinal fluid (CSF) pathological biomarkers in Alzheimer’s disease (AD)-spectrum patients. Method: A total of 39 individuals were recruited, including 23 AD patients and 16 control subjects. All subjects underwent a battery of neuropsychological examinations, CSF measurement and multimodal magnetic resonance imaging scans. Independent component analysis was used to investigate the differences of functional connectivity（FC）among the two groups based on the resting-sate functional MRI (fMRI) data. Then correlation analyses were used to estimate the potential relationship between functional network alterations and cerebral amyloid and tau burden. Result: Multiple inter- and intra-network functional connections were altered in AD patients compared to the Non ADCI group. Alterations in FC between VN and PCC, as well as the functional connections of SMN were found to be associated with the dynamic changes of CSF Tau. Compared the AD group with the non-AD CI group, the aforementioned altered functional brain connectivity, with the exception of FC in the PCC and VN, was significantly associated with a decrease in CSF Aβ Conclusion: This study provides provisional evidence that the brain functional network alterations was closely associated with CSF pathological characteristics, and these exploratory results support new research ideas for the early diagnosis of AD.
ObjectiveMovement disorders (MDs) are common in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis but are poorly studied. This study aimed to investigate the clinical characteristics of MDs and the clinical differences between patients with and without MDs in anti-NMDAR encephalitis.MethodsA retrospective study was conducted on patients with anti-NMDAR encephalitis who were first diagnosed and treated in the First People’s Hospital of Yunnan Province from January 2017 to September 2022. According to the presence or absence of MDs, all patients were divided into two groups, and the clinical manifestations, auxiliary examinations, and prognosis of the two groups were compared. Patients in the MDs group were further subgrouped by different ages (<12 years, 12–17 years, and ≥ 18 years) and genders, and the prevalence of each MD was compared in different age and gender groups.Results(1) In our study there were 64 patients, of whom 76.6% (49/64) presented with MDs; the median age of onset in patients with MDs was 21 (15,35) years and 65.3% (32/49) were female. The three most common MDs were orofacial dyskinesia (OFLD) (67.3%), dystonia (55.1%), and stereotypies (34.7%). Patients <12 years were more likely to experience chorea than patients in other age groups (p = 0.003). (2) Compared with the non-MDs group, patients in the MDs group showed higher rates of prodromal manifestations, autonomic dysfunction, consciousness disorders, as well as pulmonary infection and gastrointestinal dysfunction (all p < 0.05). Peripheral blood neutrophil to lymphocyte ratio (NLR) (p = 0.014), the proportion of cerebrospinal fluid (CSF) NMDAR antibody titers ≥1:32 (p = 0.047), ICU admission rate (p = 0.04), length of stay (p = 0.007), maximum mRS score in the course of disease (p = 0.001) and mRS score at discharge (p = 0.006) in the MDs group were significantly higher than the non-MDs group.ConclusionMDs associated with anti-NMDAR encephalitis were predominantly hyperkinetic. Chorea occurred more commonly in patients aged <12 years. Patients with MDs were prone to autonomic dysfunction, consciousness disorders, pulmonary infection, and gastrointestinal dysfunction; they had more intense inflammation, more severe disease, and a poorer short-term prognosis.
Objective:To observe the effect of escitalopram combined with repetitive transcranial magnetic stimulation (rTMS) on efficacy and attention function in patients with first-episode unipolar depression.Methods:Fifty-two first-episode initial-naive unipolar depression patients were enrolled in Department of Neurology of Guangzhou First People's Hospital from March 2022 to April 2023 were chosen. They were randomly allocated to active stimulation group ( n=27) and sham stimulation group ( n=25); both were treated with escitalopram, and active treatment or sham treatment in the left dorsolateral prefrontal cortex (DLPFC) were given for 4 weeks (5 d per week, 20 d totally). Before treatment and 2 and 4 weeks after treatment, Hamilton Depression Rating Scale (HAMD)-24 was used to evaluate depressive symptoms, and Birmingham Cognitive Screening Scale-Chinese (BCoS-C) was used to evaluate the attention function. Results:(1) In terms of depressive symptoms: HAMD-24 scores of the active stimulation group 2 and 4 weeks after treatment (20.63±2.73, 15.85±2.43) were significantly lower than those before treatment (25.74±2.68, P<0.05); HAMD-24 scores of sham stimulation group 4 weeks after treatment were also significantly lower than those before treatment ([20.48±2.33] vs. [25.80±2.57], P<0.05); HAMD-24 scores of the active stimulation group 2 and 4 weeks after treatment were significantly lower than those of sham stimulation group ( P<0.05). (2) In terms of auditory attention indicators: total correct number (selective attention) in active stimulation group 4 weeks after treatment was significantly larger than that before treatment (51.74±1.38 vs. 47.48±1.60), and the sustained index (sustained attention) was significantly lower than that before treatment (0.74±0.71 vs. 4.37±1.15, P<0.05); total correct number in active stimulation group 4 weeks after treatment was significantly larger than that in sham stimulation group (48.00±1.66), and the sustained index was significantly lower than that in sham stimulation group (3.72±1.28, P<0.05). Conclusion:Combined with escitalopram, rTMS can more effectively mitigate the depressive symptoms in first-episode unipolar depression patients, and depressive symptoms improve more quickly than attentional function.
Epilepsy of infancy with migrating focal seizure (EIMFS) is a rare drug-resistant epilepsy syndrome with characteristic migrating EEG presentation. In recent years, with increased discovery of new pathogenic genes in this syndrome, our knowledge and understanding on pathophysiological mechanisms of this syndrome have been broadened. This article systematically summarizes the genes associated with EIMFS that have been reported at home and abroad to expand clinicians' understanding of the disease and provide references for identifying the disease.
Objective:To study the correlations of hippocampal subfield volumes with cerebrospinal fluid (CSF) biomarkers in Alzheimer's disease (AD) patients.Methods:Forty-nine patients with cognitive impairment, including 30 AD patients and 19 non-AD patients, were recruited in Department of Neurology, Drum Tower Clinical College, Nanjing University of Chinese Medicine from May 2017 to December 2021. Concentrations of Aβ 1-42, total tau protein and phosphorylated tau protein in CSF were analyzed by enzyme-linked immunosorbent assay (ELISA). Volumes of 12 hippocampal subfields were calculated using FreeSurfer image analysis. Differences of clinical data, neuropsychological scores and CSF biomarker concentrations between the 2 groups were compared. Partial correlation was performed to analyze the correlations of volumes of hippocampal subfields with CSF biomarker concentrations. Results:AD patients had significantly lower Mini-mental State Examination (MMSE) scores and Aβ 1-42 concentration in CSF than non-AD patients ( P<0.05); AD patients had significantly lower volumes of the right hippocampal parasitulum, dentate gyrus and CA4 than non-AD group ( P<0.05); the right parasubiculum volume was negatively correlated with CSF Aβ 1-42 ( r=-0.445, P=0.023) and positively correlated with CSF P-tau ( r=0.393, P=0.047) in AD patients. Volumes of left hippocampus tail, parasubiculum, CA1, molecular layer, dentate gyrus, CA3 and CA4 were negatively correlated with CSF total tau ( P<0.05). No significant correlation was noted between hippocampal subfield volumes and CSF biomarker concentrations in non-AD patients. Conclusion:Some right hippocampal subfields in AD patients atrophy compared with those in non-AD patients with cognitive impairment; the right parasubiculum may play a compensatory role in disease process, while volumes of the left hippocampus decreased with increased CSF total tau.
Objective:To investigate the safety and effectiveness of emergency one-stop hybrid operation in ruptured and hemorrhagic high-grade brain arteriovenous malformations (BAVMs).Methods:Twelve patients with ruptured and hemorrhagic high-grade BAVMs who underwent emergency one-stop hybrid operation were chosen. The clinical data and efficacy of these patients were analyzed retrospectively.Results:All patients completed surgery successfully. Embolization combined with BAVMs resection was performed in 4 patients, BAVMs resection under digital subtraction angiography (DSA) was performed in 4 patients, embolization combined with balloon-assisted BAVMs resection was performed in 1 patient, balloon-assisted BAVMs resection under DSA was performed in 1 patient, embolization combined with BAVMs resection and aneurysm clipping was performed in 1 patient, and BAVMs resection combined with aneurysm clipping under DSA was performed in 1 patient. Intraoperative DSA showed residual vascular malformation in 1 patient and complete resection in other 11 patients. No surgical complications occurred. Two patients presented symptoms of delayed epilepsy after discharge. Six months after operation, 8 patients had good prognosis (Glasgow Outcome Scale [GOS] scores≥4), 4 had poor prognosis (GOS scores of 1-3), and no death occurred. CTA or DSA in all patients 6 months after operation found no residual or recurrent vascular lesions.Conclusion:Emergency one-stop hybrid operation has high complete occlusion rate and low surgical complication incidence in ruptured and hemorrhagic high-grade BAVMs, which is worthy of clinical application.
Objective:To investigate the efficacy and safety of intracavernous sinus spring coil+Onyx gel embolization combined with proximal spring coil occlusion of the ophthalmic vein in cavernous sinus-dural arteriovenous fistula (CS-DAVF).Methods:Thirty-seven patients with CS-DAVF accepted intracavernous sinus spring coil+Onyx gel embolization combined with proximal spring coil occlusion of ophthalmic vein in Department of Radiology and Interventional Medicine, First Affiliated Hospital of Zhengzhou University were selected. The clinical data and therapeutic efficacy of these patients were retrospectively analyzed.Results:All 37 patients had different degrees of ocular symptoms at the time of treatment: 31 (83.8 %) had conjunctival congestion, 16 (43.2 %) had exophthalmos, and 14 (37.8 %) had obvious periorbital vascular murmur. Endovascular intervention was performed in all patients via venous routes, including inferior petrous sinus approach ( n=34), ophthalmic vein approach ( n=2), and facial vein approach ( n=1). Immediate postoperative DSA showed that 31 patients had complete occlusion of the fistula, and 6 patients had near-total occlusion (disappeared drainage of the thickened ophthalmic vein or obviously slowed down drainage). Thirty-five patients had ocular oedema of varied degrees and then gradually reduced (lasting for 1-2 weeks), and all the ocular congestion and vascular murmurs disappeared before discharging from the hospital. Four patients had postoperative palsy of the motor and abducens nerves, which improved significantly after 1-5 months; 1 patient had diplopia in combination with abducens nerve palsy; all symptoms alleviated after 2 months of nutritional nerve medication. Follow up in Outpatient Clinic or telephone was performed for (12.1±4.4) months, ranged for 6.5-21.3 months; symptoms of ocular congestion and edema disappeared in all patients at the last follow-up. Followed-up DSA at 6 months showed no recurrence of CS-DAVF. Conclusion:Intracavernous sinus spring coil+Onyx gel embolisation combined with proximal spring coil occlusion of the ophthalmic vein is safe and effective in CS-DAVF.
Recent studies have found that the pathological changes of Tau proteinopathy, such as Alzheimer's disease (AD) and progressive supranuclear palsy (PSP), involve transmission or circulatory disturbance of synaptic vesicles. This article reviews the relations of AD/PSP with circulatory disturbance of synaptic vesicles and explore the pathogenesis of these diseases, aiming to provide a new perspective for new therapeutic drugs.
Objective:To investigate the effects of Xiangshao granules on behavior and oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs) in the medial prefrontal cortex (mPFC) of post-stroke depression (PSD) mice.Methods:Eighty C57BL/6 mice were divided into sham-operated group, middle cerebral artery occlusion (MCAO) group, PSD+PBS group, and PSD+Xiangshao group ( n=20). PSD models were constructed using mild chronic unforeseeable stress (CUMS) and solitary feeding after MCAO. MCAO models were evaluated by laser speckle contrast imaging (LSCI), modified neurological severity score (mNSS) and TTC staining. PSD models were evaluated by body mass, sugar and water preference test and tail suspension test. After PSD modeling, mice in the sham-operated group, MCAO group, and PSD+PBS group were given 0.2 mL PBS, while mice in the PSD+Xiangshao group was given Xiangshao granules at dosage of 60 mg/kg (dissolved in 0.2 mL PBS); all were given via intragastric administration once a d for 28 d. Number of OPCs and OLs in mPFC was detected by immunofluorescence. Expressions of myelin basic protein (MBP) and phosphatidylinositol 3-kinase/serine/threonine kinase/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway proteins in mPFC were detected by Western blotting. Results:(1) Model verification results: LSCI showed obvious changes of cerebral blood flow in the middle cerebral artery supply area before, during and after MCAO; TTC staining showed typical red non-infarct area and white infarct area in MCAO group, PSD+PBS group and PSD+ Xiangshao group; mNSS scores in MCAO group, PSD+PBS group and PSD+ Xiangshao group were all >4, without significant differences ( P>0.05); the MCAO model was successfully constructed. After PSD and before treatment, the PSD+PBS group and PSD+Xiangshao group had significantly decreased body weight and sugar-water preference, and statistically prolonged tail suspension immobilization time compared with sham-operated group and MCAO group ( P<0.05); the PSD model was successfully constructed. (2) Results of mouse behavior experiment after treatment: significant differences in body weight, sugar-water preference and tail suspension time were noted in mice of the 4 groups 28 d after treatment ( P<0.05); PSD+Xiangshao group had significantly increased body weight and sugar-water preference and decreased tail suspension immobilization time compared with PSD+PBS group ( P<0.05). (3) Number of OPCs (Olig2 +PDGFRa +), proliferative OPCs (Ki-67 +PDGFRa +, EdU +PDGFRa +) and OLs (Olig2 +CC1 +), and relative MBP, p-PI3K, p-AKT and p-mTOR protein expressions in mPFC of the 4 groups were significantly different ( P<0.05); compared with those in PSD+PBS group, the above cell number and relative protein expressions in PSD+Xiangshao group were significantly increased ( P<0.05). Conclusion:Xiangshao granules can promote the OPCs proliferation and OLs maturation by activating PI3K/AKT/mTOR signaling pathway in mPFC, thus playing a role in PSD.
Objective:To investigate the clinical characteristics of patients with epithelioid glioblastoma (ep-GBM) and their influencing factors for survival.Methods:Sixteen ep-GBM patients admitted to Department of Neurosurgery, First Affiliated Hospital of Zhengzhou University from August 2015 to March 2022 were chosen. Clinical data such as age, gender, maximum tumor diameter, degrees of tumor resection, treatments, and immunohistochemical staining-related indexes were obtained. Survival curves of the patients were plotted by Kaplan-Meier method, and differences of progression-free survival (PFS) and overall survival (OS) among patients with different clinical characteristics were compared. Log-rank test was used to compare the survival rates, and Cox proportional risk regression model was constructed to analyze the influencing factors for PFS and OS.Results:In these 16 patients, median OS was 11.8 months and median PFS was 7.0 months. Significant differences in PFS and OS were noted between groups of age<32 years and age≥32 years, between groups of maximum tumor diameter<4.8 cm and diameter≥4.8 cm, and between groups of positive p53 expression and negative p53 expression ( P<0.05). Log-rank test indicated that OS and PFS ratios were significantly different between groups of age<32 years and age≥32 years, between groups of maximum tumor diameter<4.8 cm and diameter≥4.8 cm, between S100 positive group and S100 negative group, between Olig-2 positive group and Olig-2 negative group, and between groups of positive p53 expression and negative p53 expression ( P<0.05). Cox proportional hazard regression model showed that age ( HR=1.070, 95% CI: 1.013-1.134, P=0.016), preoperative maximum tumor diameter ( HR=2.150, 95% CI: 1.142-4.055, P=0.018) and Olig-2 expression ( HR=0.040, 95% CI: 0.003-0.498, P=0.013) had influences in PFS; preoperative maximum tumor diameter ( HR=2.350, 95%CI: 1.149-4.798, P=0.019) and Olig-2 expression ( HR=0.080, 95% CI: 0.007-0.972, P=0.047) had influences in OS. Conclusion:Older ep-GBM patients are prone to progress after surgery; ep-GBM patients with larger tumor diameter and negative Olig-2 expression likely progress and have poor prognosis after surgery.
Objective:To analyze the clinical characteristics of patients with anterior and posterior circulation large vessel occlusion ischemic stroke and clinical prognoses after successful endovascular recanalization.Methods:A retrospective analysis was performed; 170 patients with large vessel occlusive ischemic stroke, admitted to Stroke Center, Second Hospital of Dalian Medical University from January 2016 to September 2022 were chosen; these patients had modified Thrombolysis in Cerebral Infarction (mTICI) 2b or 3 after endovascular treatment. These patients were divided into anterior-circulation large vessel occlusion group ( n=138) and posterior-circulation large vessel occlusion group ( n=32) according to the locations of vessel occlusion. Clinical data, parameters related to endovascular treatment, and clinical prognoses of the 2 groups were collected and compared. Results:Posterior-circulation large vessel occlusion group had significantly higher percentages of male patients and patients with atherosclerotic type (81.3% vs. 61.6%; 78.1% vs. 47.1%), significantly higher ratio of neutrophil to lymphocyte and NIHSS scores (3.78 [1.93, 10.86] vs. 2.77[1.77, 4.72]; 20.50±8.96 vs. 14.83±4.67), significantly lower percentage of patients with atrial fibrillation (21.9% vs. 58%), and significantly longer times from onset to puncture, onset to recalculation, admission to puncture, and admission to recalculation (367.50 [246.25, 630.00] min vs. 240.00 [198.75, 330.00]; 515.00 [292.50, 701.25] vs. 345.50 [270.00, 425.75] min; 163.00 [123.25, 218.50] min vs. 125.50 [97.00, 161.00]; 258.00 [200.25,389.00] vs. 219.50 [178.00, 276.25]) than anterior-circulation large vessel occlusion group ( P<0.05). The NIHSS scores 24 h after endovascular treatment, NIHSS scores at discharge, and mortality within 90 d in posterior-circulation large vessel occlusion group were significantly higher than those in anterior-circulation large vessel occlusion group (21.31±9.23 vs. 15.74±6.53; 25.5 [4.25, 40.25] vs. 10.00 [4.00, 18.25]; 40.6% vs. 20.3%, P<0.05); however, no significant differences in symptomatic intracranial hemorrhage, incidence of intracranial hemorrhage, in-hospital mortality or 90-d good prognosis were noted between the 2 groups ( P>0.05). Conclusion:Posterior circulation large vessel occlusion ischemic stroke patients have higher neurological impairment at onset than anterior circulation acute large vessel occlusion ischemic stroke patients; both patients enjoy similar results in terms of 90-d good prognosis and complications, but 90-d mortality is higher than that in anterior ones.
Epilepsy is one of the common neurological diseases in the nervous system. The susceptibility, seizure frequency and drug efficacy in epilepsy vary across different regions, possibly related to living environment and genetic factors. The unique geographical environment and dietary habits of people living on plateaus are associated with occurrence and development of epilepsy to some extent. However, research on the correlation between plateau environment and epilepsy is currently limited. This paper comprehensively reviews the correlation between plateau environment and epilepsy, aiming to better understand the real scenarios and pathogenesis of epilepsy and offer valuable reference for prevention, diagnosis and treatment of epilepsy in plateau areas.
In recent years, a large number of studies have found that Parkinson's disease (PD) patients often complicate with osteoporotic fracture, which may be related to decreased dopamine transmitters, PD risk gene mutations, mitochondrial dysfunction, vitamin D reduction, anti-PD drug use, autonomic nervous dysfunction and intestinal microflora disorders. Therefore, this paper reviews the current research progress on the pathogenesis of osteoporotic fracture in PD patients to provide theoretical basis for co-morbid treatment of PD and osteoporotic fracture.
Recent studies have found that immune factors exist in the pathogenesis of various sleep disorders, and sleep disorders can occur before onset of neurological autoimmune syndrome or accompany in the disease progression and recovery. Video-polysomnography can provide digital and objective information on various sleep disorders, which is helpful for in-depth clinical research on neurological autoimmune related sleep disorders. This article reviews the recent advance in video-polysomnography features of various neurological autoimmune related sleep disorders, aiming to provide reference and guidance for clinical diagnosis and evaluation.
Depression is a mental disease that seriously threatens life and health, and its pathogenesis is complicated. Recent studies have found that altitude is one of the important factors leading to depression. As an important transcription factor under hypoxic condition, hypoxia-inducible factor-1 regulates acute hypoxia, and upregulates neurotrophic factor and 5-hydroxytryptamine, thus exerting antidepressant effect by promoting brain metabolism; hypoxia-inducible factor-2 regulates chronic hypoxia, promotes inflammation and aggravates depression. This article focuses on the related research on hypoxia-inducible factors and pathogenesis of high altitude depression, to further explore the pathogenesis and prevent high altitude depression.
Objective:To investigate the role of NG2 cells in generating and maintaining neuropathic pain in rats after spinal cord injury (SCI).Methods:According to random number table method, 100 healthy adult male SD rats were divided into control group ( n=20, without any intervention), sham-operated group ( n=40, exposed T 10 segment without spinal cord impact) and SCI group ( n=40, exposed T 10 segment and constructed SCI model by improved Allen's method). One d before, and 14, 21 and 28 d after surgery, Von Frey fiber probe was used to detect the rat hindlimb mechanical withdrawal threshold (MWT); immunofluorescent staining was used to detect the proportion of NG2-positive cells in spinal dorsal horn cells; Western blotting was used to detect chondroitin sulfate proteoglycan (CSPG) expression in spinal dorsal horn of rats. Results:Fourteen, 21 and 28 d after surgery, SCI group had significantly lower hindlimb MWT, and significantly higher proportion of NG2-positive cells in spinal dorsal horn cells and CSPG expression in spinal dorsal horn than control group and sham-operated group ( P<0.05). One d before, and 14, 21 and 28 d after surgery, in SCI group, hindlimb MWT decreased firstly and increased secondly, proportion of NG2-positive cells in spinal dorsal horn cells increased firstly and decreased secondly, and CSPG expression in spinal dorsal horn increased firstly and decreased secondly. Except for those 21 and 28 d after surgery, hindlimb MWT, proportion of NG2-positive cells in spinal dorsal horn cells, and CSPG expression in spinal dorsal horn showed significant differences between each two time points ( P<0.05). In SCI group, hindlimb MWT was negatively correlated with proportion of NG2-positive cells in spinal dorsal horn cells ( r=-0.876, P<0.001), and CSPG expression was positively correlated with proportion of NG2-positive cells in spinal dorsal horn cells ( r=0.927, P<0.001). Conclusion:NG2 cell proliferation and increased CSPG expression secreted by NG2 cells in spinal cord tissues after SCI generate and maintain neuropathic pain.
Objective:To explore the characteristics of self-referential network (SRN) functional connectivity in subjective cognitive decline (SCD) patients with normal and impaired metacognition.Methods:Seventy-one subjects were selected from Alzheimer's Disease Neuroimaging Initiative (ADNI) database, with 25 cognitively normal controls and 46 SCD patients. The metacognitive level of SCD patients was assessed by Everyday Cognition Scale (ECog), and then, they were divided into a metacognitively normal group ( n=25, metacognitive scores>-0.074) and a metacognitively impaired group ( n=21, metacognitive scores≤-0.074). Results of Geriatric Depression Scale (GDS), Montreal Cognitive Scale (MoCA), Mini‐Mental State Examination (MMSE), Rey Auditory Word Learning Test (RAVLT), Logical Memory Scale, expressions of pathological markers (cerebrospinal fluid β-amyloid protein [Aβ], total tau protein [t-tau] and phosphorylated tau protein [p-tau]), brain glucose metabolism, and functional magnetic resonance imaging (fMRI) were collected and compared among the 3 groups. Independent component analysis (ICA) was used to extract SRN and analyze the different brain regions among the 3 groups; Pearson correlation was used to analyze the correlations of SRN functional connectivity changes with cognitive scales and pathological markers. Results:No significant differences in demographic characteristics (age and gender), scores of GDS, MoCA and MMSE, or levels of Aβ, t-tau, p-tau and brain glucose metabolism were noted among the 3 groups ( P>0.05). The metacognitive scores in metacognitively impaired group were significantly lower than those in metacognitively normal group and cognitively normal controls ( P<0.05). Significant difference in the functional connectivity of bilateral anterior cingulate gyrus and bilateral orbitofrontal cortex was noted among the 3 groups (TFCE-FWE correction, P<0.01, voxel>100); compared with the cognitively normal controls, the metacognitively impaired group showed significantly decreased functional connectivity of bilateral orbitofrontal cortex, while the metacognitively normal group showed enhanced functional connectivity of bilateral orbitofrontal cortex (TFCE-FWE correction, P<0.01, voxel>100); compared with the metacognitively normal group, the metacognitively impaired group had statistically decreased functional connectivity of bilateral orbitofrontal cortex (TFCE-FWE correction, P<0.01, voxel>100). Further correlation analysis showed that difference value of functional connectivity of bilateral orbitofrontal cortex between metacognitively impaired group and cognitively normal controls was negatively correlated with RAVLT-immediate scores ( r=-0.445, P=0.043); difference value of functional connectivity of bilateral orbitofrontal cortex between metacognitively impaired group and metacognitively normal group was negatively correlated with RAVLT-immediate scores ( r=-0.463, P=0.034). Conclusion:SCD patients with different metacognitive levels have characteristic SRN functional connectivity changes; impaired metacognition may be an early feature of Alzheimer's disease.
Objective:To investigate the influence of long non-coding RNA (lncRNA) DIO3OS in ketamine-induced neurotoxicity and its mechanism in mouse hippocampal neurons.Methods:(1) Primary mouse hippocampal neurons were isolated and cultured; CCK-8 assay was used to detect the viability of cells treated with different concentrations of ketamine (0, 25, 50, 100, 200 μmol/L), and qPCR was used to detect DIO3OS mRNA expression. (2) Hippocampal neurons were divided into 4 groups: control group, ketamine group (cultured with 50 μmol/L ketamine for 24 h), ketamine+pc group (transfected with pcDNA3.1 plasmid for 48 h, and then cultured with 50 μmol/L ketamine for 24 h), and ketamine+DIO3OS group (transfected with pcDNA3.1-DIO3OS plasmid for 48 h, and then cultured with 50 μmol/L ketamine for 24 h); cell viability was detected by CCK-8 assay; lactic dehydrogenase (LDH) release was determined by LDH cytotoxicity assay kit; cell apoptosis was detected by flow cytometry; mRNA expressions of DIO3OS and brain-derived neurotrophic factor ( BDNF) were examined by qPCR; protein expressions of polypyrimidine tract-binding protein 1 (PTBP1) and BDNF were detected by Western blotting. (3) Total proteins of routinely cultured neurons were extracted, and RNA Pull-Down assay was used to detect whether DIO3OS mRNA and BDNF mRNA could directly bind to PTBP1 protein. (4) Hippocampal neurons were divided into ketamine+DIO3OS+si-NC group (co-transfected with pcDNA3.1-DIO3OS plasmid and si-NC plasmid for 48 h, and then cultured with 50 μmol/L ketamine for 24 h) and ketamine+DIO3OS+si-PTBP1 group (co-transfected with pcDNA3.1-DIO3OS plasmid and si-PTBP1 plasmid for 48 h, and then cultured with 50 μmol/L ketamine for 24 h); qPCR was used to examine the mRNA expressions of DIO3OS and BDNF; Western blotting was used to detect the protein levels of PTBP1 and BDNF. (5) Hippocampal neurons were divided into ketamine group (cultured with 50 μmol/L ketamine for 24 h), ketamine+si-DIO3OS group (transfected with si-DIO3OS plasmid for 48 h, and then cultured with 50 μmol/L ketamine for 24 h), ketamine+si-PTBP1 group (transfected with si-PTBP1 plasmid for 48 h, and then cultured with 50 μmol/L ketamine for 24 h), and ketamine+si-DIO3OS+si-PTBP1 group (co-transfected with si-DIO3OS plasmid and si-PTBP1 plasmid for 48 h, and then cultured with 50 μmol/L ketamine for 24 h); qPCR was used to examine the mRNA expressions of DIO3OS and BDNF; Western blotting was used to detect the BDNF protein expression. (6) Hippocampal neurons were divided into ketamine+DIO3OS+si-NC group (co-transfected with pcDNA3.1-DIO3OS plasmid and si-NC plasmid for 48 h, and then cultured with 50 μmol/L ketamine for 24 h), ketamine+DIO3OS+si-BDNF group (co-transfected with pcDNA3.1-DIO3OS plasmid and si-BDNF plasmid for 48 h, and then cultured with 50 μmol/L ketamine for 24 h); cell viability was detected by CCK-8 assay; LDH release was determined by LDH cytotoxicity assay kit; cell apoptosis was detected by flow cytometry. Results:(1) Compared with 0 μmol/L ketamine, 25, 50, 100 and 200 μmol/L ketamine could significantly inhibit the cell viability and DIO3OS mRNA expression ( P<0.05). (2) Compared with control group, ketamine group had significantly decreased DIO3OS mRNA expression and cell viability, significantly increased LDH release and apoptotic rate, and statistically inhibited BDNF mRNA and protein expressions and PTBP1 protein expression ( P<0.05); compared with ketamine+pc group, ketamine+DIO3OS group had significantly increased DIO3OS mRNA expression and cell viability, significantly decreased LDH release and apoptotic rate, significantly elevated BDNF mRNA and protein expressions ( P<0.05). (3) RNA Pull-Down assay showed that Bio-labeled DIO3OS (Bio-DIO3OS) and Bio-labeled BDNF (Bio-BDNF) could adsorb PTBP1 protein, while Bio-labeled antisense strands of DIO3OS or BDNF (Bio-DIO3OS-AS and Bio-BDNF-AS) could not adsorb PTBP1 protein. (4) Compared with ketamine+DIO3OS+si-NC group, ketamine+DIO3OS+si-PTBP1 group had significantly inhibited BDNF mRNA and protein expressions and PTBP1 protein expression ( P<0.05); no significant difference was noted in DIO3OS mRNA expression ( P>0.05). (5) Compared with ketamine group, ketamine+si-DIO3OS and ketamine+si-DIO3OS+si-PTBP1 groups had significantly decreased DIO3OS mRNA expression ( P<0.05); compared with ketamine group, ketamine+si-DIO3OS and ketamine+si-PTBP1 groups had significantly decreased BDNF mRNA and protein expressions ( P<0.05); compared with ketamine+si-DIO3OS and ketamine+si-PTBP1 groups, ketamine+si-DIO3OS+si-PTBP1 group had significantly elevated BDNF mRNA and protein expressions ( P<0.05). (6) Compared with ketamine+DIO3OS+si-NC group, ketamine+DIO3OS+si-BDNF group had significantly reduced cell viability, and significantly increased LDH release and apoptotic rate ( P<0.05). Conclusion:LncRNA DIO3OS expression is decreased in ketamine-induced primary mouse hippocampal neurons; DIO3OS overexpression can alleviate ketamine-induced neurotoxicity in mouse hippocampal neurons by regulating BDNF expression via binding to PTBP1.
Pituitary neuroendocrine tumors (PitNETs) are the second common central nervous system tumors. Patients often present with headache, vision loss, visual field defects, and cognitive dysfunction. Cognitive function is the ability of the brain to acquire, analyze and process external information; once the patient has serious cognitive dysfunction, it will bring heavy burden to the family and society. This article summarizes the cognitive functions in patients with PitNETs from perspectives of hormone, anatomical structures around the pituitary, tumor volume, treatment, and cognitive function assessment, in order to provide research ideas in elucidating relevant mechanisms in the future and provide basis for formulating rehabilitation plans for patients.
