Objective:To explore the effect of pentraxin 3 (PTX3) on memory improvement and Aβ expression in Alzheimer's disease (AD) model mice.Methods:(1) Ten 5-month-old 5×FAD mice were randomly divided into PTX3 group and model group ( n=5); 5 C57BL/6 wild-type mice at the same age were selected as control group; mice in the PTX3 group and control group were stereotactically injected 4 μL 0.5 g/L PTX3 or same dose of phosphate buffered saline (PBS); Morris water maze test was used to detect the learning and memory abilities, Y maze test was used to detect the short-term memory, and ELISA was used to obsevre the contents of Aβ 40 and Aβ 42 in the brain hemisphere. (2) Twenty-five 3-month-old 5×FAD mice were randomly divided into model group, 2 μg/kg PTX3 group, 4 μg/kg PTX3 group, 8 μg/kg PTX3 group, and 16 μg/kg PTX3 group ( n=5); 5 C57BL/6 wild-type mice at the same age were selected as control group; mice in the PTX3 groups were intranasally injected 2, 4, 8, and 16 μg/kg PTX3, respectively; those in the model group and control group were intranasally injected same dose of PBS; injection was given once every 96 h for a total of 7 times. Morris water maze test was used to detect the learning and memory abilities, Y maze test was used to detect the short-term memory, and ELISA was used to obsevre the contents of Aβ 40 and Aβ 42 in the hippocampus. Results:(1) Compared with the model group, the PTX3 group had significantly shorter platform latency, higher percentage of exploration time and higher percentage of spontaneous alternations ( P<0.05). Compared with those in model group ([63.38±21.42] pg/mL, [29.77±6.11] pg/mL), the concentrations of Aβ 40 and Aβ 42 in the brain tissues of PTX3 group ([15.87±2.11] pg/mL, [16.55±1.95] pg/mL) were statistically lower ( P<0.05). (2) Compared with the model group, the 16 μg/kg PTX3 group had significantly shorter escape latency and higher percentage of exploration time ( P<0.05); compared with the model group, the 2 μg/kg PTX3 group and 16 μg/kg PTX3 group had significantly higher percentage of spontaneous alternations ( P<0.05). The contents of Aβ 40 and Aβ 42 in the hippocampus of 8 μg/kg PTX3 group and 16 μg/kg PTX3 group were statistically lower compared with those in the model group ( P<0.05). Conclusion:PTX3 may attenuate cognitive deficits and decrease Aβ expression in the brain or hippocampus tissues of 5×FAD mice with AD.

Objective:To explore the pathogenesis of flunarizine-induced parkinsonism from gut-brain axis perspective.Methods:Thirty male C57BL/6 mice were randomly divided into control group and flunarizine group ( n=15). Mice in the control group were given 0.1 mL 50% polyethylene glycol 400+50% saline by gavage once/d for 2 weeks, while mice in the flunarizine group were given 6 mg/mL flunarizine+50% polyethylene glycol 400+50% saline by gavage at a daily dose of 30 mg/kg for 2 weeks. Body mass was recorded 1, 3, 5, 7, 10 and 14 d after drug administration, and motor function was assessed by rotarod test 14 d after drug administration; 16s RNA sequencing was performed in the feces to observe the intestinal flora; intestinal transit function was detected by Evans blue by gavage; and then, the mice were sacrificed and homogenate or frozen sections (brain and intestinal tissues) were prepared; dopamine-ergic neuron expression was detected by Western blotting; RT-qPCR was applied to detect the expressions of inflammatory factors in the substantia nigra, and immunofluorescent staining was used to detect the expressions of ZO-1 and Claudin-5 in the intestinal epithelial tissues. Results:Compared with the control group, the flunarizine group had lower body mass ratio 1, 3, 5, 7, 10 and 14 d after drug administration (ratio to body mass before drug administration). Compared with the control group, the flunarizine group had significantly shortened residence time in rod rotating and lower rotational speed when falling ( P<0.05). Compared with the control group, the flunarizine group had decreased tyrosine hydroxylase protein in the substantia nigra without significant difference ( P>0.05). Compared with the control group, the flunarizine group had significantly increased interleukin-6 and tumor necrosis factor-α in the substantia nigra (1.00±0.00 vs. 2.79±0.83; 1.00±0.00 vs. 3.39±1.37), significantly lower intestinal Evans blue propulsion rate (80.67%±4.51% vs. 50.67%±6.03%), and statistically decreased ZO-1 and Claudin-5 expressions in the colonic epithelial tissues (27.01±1.41 vs. 16.32±2.83; 37.00±2.80 vs. 24.52±2.12, P<0.05). Totally, 576 microorganisms were noted in both control group and flunarizine group, 744 in the control group alone, and 634 in the flunarizine group alone. The intestinal flora β diversity indices in the 2 groups were significantly different based on weighted Unifrac-principle coordinates analysis (PCoA, PCoA1: 39.88%; PCoA2: 30.69%). Compared with the control group, the microbial colony structure of mice in flunarizine group was dominated by phylum thick-walled bacteria and phylum warty microbacteria, and by families Muribaculaceae, Lachnospiraceae and Akkermansiaceae. Compared with the control group, the flunarizine group had significantly decreased relative abundance of Ackermannia spp. and Lactobacillus spp. in the intestinal flora ( P<0.05). Conclusion:Flunarizine may contribute to the pathogenesis of DIP by causing structural disturbances in the intestinal flora and inducing neuroinflammation based on the gut-brain axis.

Objective:To evaluate the clinical efficacy and safety of stereotactic surgery in patients with refractory mental disorders.Methods:A retrospective analysis was performed; clinical data, postoperative complications and medication intake of 149 patients with refractory mental disorders accepted stereotactic surgery in Department of Neurosurgery, People's Hospital, Wuhan University from August 2019 to December 2023 were collected. Outcomes were assessed at 1, 6, 12, and 24 months after surgery by Clinical Global Impression-Global Improvement (CGI-GI). Before and 1, 6, and 12 months after surgery, severities were assessed by Clinical Global Impression-Severity of Illness (CGI-SI); cognition was assessed by Montreal Cognitive Assessment (MoCA); positive and negative symptoms were evaluated by Positive and Negative Symptom Scale (PANSS); psychotic symptoms were evaluated by Brief Psychiatric Rating Scale (BPRS) and Symptom Checklist 90 (SCL-90); obsessive-compulsive symptoms, depressive symptoms, anxiety symptoms and manic symptoms were assessed by Yale-Brown Obsessive-Compulsive Symptoms Scale (Y-BOCS), Beck Depression Inventory (BDI)-II, Beck Anxiety Inventory (BAI), and Young Mania Rating Scale (YMRS), respectively; social functioning and quality of survival were evaluated by Social Disability Screening Schedule (SDSS) and World Health Organization Quality of Life-Bref Form (WHOQOL-BREF).Results:(1) Increased sleep was noted in 47 patients and fatigue in 38 patients within 1 week after surgery. Behavioral laziness and emotional apathy were still presented at 1 month after surgery in 6 patients, and complications disappeared in the rest patients. Mildly reduced initiative was presented at 12 months after surgery in 5 patients. (2) CGI-GI indicated that 149 patients were followed up 1 month after surgery with an overall efficiency of 85.90%; 135 patients were followed up at 6 months after surgery with an overall efficiency of 83.21%, 106 patients were followed up at 12 months after surgery with an overall efficiency of 79.24%, and 63 patients were followed up at 24 months after surgery with an overall efficiency of 80.95%. (3) Compared with those before surgery, significantly lower BPRS scores, significantly lower PANSS positive, negative, and overall scores, statistically lower BAI, BDI-II, YMRS, and MOAS scores, significantly lower Y-BOCS obsessional thinking, compulsive behavior and total scores, significantly higher WHOQOL-BREF (physical and psychological domains) scores, and significantly lower SDSS and SCL-90 scores were noted in patients at 1, 6, and 12 months after surgery ( P<0.05). (4) At 12 months after surgery, withdrawal drug was noted in 13 patients, reduced drug in 38, same dose in 52, and increased drug in 2 patients. Conclusion:Stereotactic surgery can obviously improve obsession, anxiety, depression, mania and aggression, and modify social functioning and quality of survival in patients with refractory mental disorders, enjoying good safety.

Objective:To investigate the alterations in brain dynamic functional network connectivity (dFNC) and their significance in Parkinson's disease (PD) patients with postural instability/gait difficulty (PIGD).Methods:Ninety PD patients admitted to Department of Neurology, First Affiliated Hospital of Nanjing Medical University from May 2016 to August 2019 were recruited, and 54 healthy controls matched with gender and age were chosen; their clinical data and resting-state functional MRI (rs-fMRI) data were collected. PD patients were divided into PD with PIGD (PD-PIGD) group ( n=49) and PD without PIGD (PD-non-PIGD) group ( n=41) according to Unified Parkinson's Disease Rating Scale (UPDRS) scores. Independent component analysis (ICA), sliding window method and k-means clustering were used to analyze the dFNC and compare among groups. Correlations of dFNC alterations with clinical scales were verified by partial correlation analysis. Results:Four repeated recurring functional connectivity states were identified, and PD-PIGD patients had high frequency in state 3 (44%) and state 2 (23%) of the low dFNC. In terms of dFNC time attributes, PD-PIGD patients had longer mean dwell time in state 3 than PD-non-PIGD patients and had lower number of transitions in state 3 than PD-non-PIGD patients and healthy controls, with significant differences ( P<0.05); PD-PIGD patients had significantly higher fractional windows and statistically longer mean dwell time in state 2 than healthy controls ( P<0.05). In terms of dFNC strengths, compared with healthy controls, PD-PIGD patients showed significantly decreased functional connectivity within default mode network (DMN, between medial superior frontal gyrus and precuneus) and auditory network (AN, between superior temporal gyrus and middle temporal gyrus), but significantly increased functional connectivity between sensorimotor network (SMN, supplementary motor area) and DMN (precuneus) in state 2 ( P<0.05, false discovery rate [FDR]-corrected). Partial correlation analysis indicated positive correlation between mean dwell time in state 3 and PIGD scores in PD-PIGD patients ( r=0.450, P=0.039). Conclusion:PD-PIGD patients exhibit specific dFNC, mainly characterized by low connectivity of the brain functional network and prolonged dwell time; local functional network domains often separate between DMN, AN and SMN networks and within the networks.

Objective:To investigate the risk factors for aneurysm rupture and post-intervention complications in intracranial arterial stenosis patients with intracranial aneurysms.Methods:A retrospective analysis was performed; 238 intracranial arterial stenosis patients with intracranial aneurysms (306 intracranial aneurysms) admitted to Cerebrovascular Disease Department, Neurosurgery Center, Zhujiang Hospital, Southern Medical University from January 2018 to August 2022 were chosen. Ruptured group and unruptured group were divided according to the rupture of intracranial aneurysms. Additionally, 139 patients who underwent interventional therapy and had complete follow-up data were divided into 2 groups according to occurrence of post-intervention complications. Univariate and multivariate Logistic regression analyses were used to identify the risk factors for aneurysm rupture and post-intervention complications.Results:(1) Of 238 patients, 269 unruptured aneurysms and 37 ruptured aneurysms were noted. Univariate regression analysis showed that significant difference was noted between the ruptured group and unruptured group in female ratio, aneurysm distribution, proportion of irregular shaped aneurysms, percentages of patients with increased white blood cell count, neutrophil count, total cholesterol and D-2 polymer, and percentage of patients with decreased blood lymphocyte count ( P<0.05). Multivariate Logistic regression analysis showed that irregular shaped aneurysms ( OR=12.393, 95% CI: 4.114-37.332, P<0.001), elevated neutrophil count ( OR=18.753, 95% CI: 6.555-53.648, P<0.001), and increased D-2 polymer ( OR=4.410, 95% CI: 1.758-11.065, P=0.002) were independent risk factors for aneurysm rupture in intracranial arterial stenosis patients with intracranial aneurysms. (2) Of the 139 patients, 57 had complications and 82 had no complications. Univariate regression analysis showed that the proportion of patients with hypertension history, distribution of arterial stenosis, and proportion of patients with elevated blood D-2 polymer were significantly different between patients with and without complications ( P<0.05); while multivariate Logistic regression analysis did not identify these 3 indexes as independent risk factors for post-intervention complications ( P>0.05). Conclusion:Patients with irregular shaped aneurysms, elevated blood neutrophil count and D-2 polymer trend to have aneurysm rupture; hypertension history, arterial stenosis, and elevated D-2 polymer have impact on postoperative complications in intracranial arterial stenosis patients with intracranial aneurysms.

Objective:To investigate the clinical manifestations, serological and cerebrospinal fluid test results for syphilis, imaging features, and prognoses of cerebral syphilitic gumma.Methods:The clinical data of 1 patient with cerebral syphilitic gumma admitted to Department of Neurology, Second Affiliated Hospital of Soochow University in March 2023 were retrospectively analyzed. Papers about cerebral syphilitic gumma were searched from journals in Journal Citation Reports Q1 from 2000 to 2019, journals from 2020 to 2024 in PubMed, WOS, Embase, and Scopus databases, and journals from 2000 to 2024 in Wanfang Database, CNKI, and VIP database; the clinical data of 54 patients with cerebral syphilitic gumma reported in above databases and 1 patient in our hospital were collected for pooled analysis.Results:The main clinical manifestations of 55 cerebral syphilitic gumma patients included headache (32, 58.2%), lateral limb/facial weakness (25, 45.5%), nausea and vomiting (14, 25.5%), dizziness (11, 20.0%), sensory disturbances (10, 18.2%), blurred vision (7, 12.7%), seizure (5, 9.1%)), hearing loss (5, 9.1%), tinnitus (5, 9.1%), memory loss (3, 5.5%), aphasia (3, 5.5%), dysarthria (2, 3.6%), drop attack (2, 3.6%), weakness in opening eyes (2, 3.6%), unresponsiveness (1, 1.8%), Argyll-Robertson pupil (1, 1.8%), tabes dorsalis gait (1, 1.8%), and fever (1, 1.8%). In 51 patients who reported complete serologic test results, 45 patients (88.2%) were positive for non-specific antibodies to syphilis, and all patients were positive for specific antibodies to syphilis. In 34 patients underwent cerebrospinal fluid examination, 25 (73.5%) were positive for non-specific antibodies to syphilis, and 32 (94.1%) were positive for specific antibodies to syphilis. Isolated intracranial lesion (43, 78.2%) was mostly common in imaging test, and the frequently involved cranial sites were, orderly, the frontal lobe (14, 25.5%), parietal lobe (14, 25.5%), temporal lobe (5, 9.1%), frontotemporal lobe (3, 5.5%), frontoparietal lobe (2, 3.6%), parieto-occipital lobe (2, 3.6%), nucleus pulposus (1, 1.8%), clivus (1/55, 1.8%), and cerebral peduncle of the midbrain (1, 1.8%). Thirty patients (54.5%) were misdiagnosed as having other intracranial space-occupied diseases, orderly, glioma (11, 36.7%), metastatic tumors (5, 16.7%), meningiomas (4, 13.3%), other unexplained intracranial space-occupying (4, 13.3%), brain abscess (3, 10.0%), cavernous hemangioma (1, 3.3%), intracranial lymphoma (1, 3.3%), auditory nerve and pituitary tumors (1, 3.3%). Of the 42 patients who reported prognosis after anti-syphilitic treatments, 41 had varying degrees of improvement, and one died of brain herniation.Conclusion:Because of atypical clinical manifestations and lack of clear diagnostic criteria, cerebral syphilitic gumma is often misdiagnosed as intracranial tumors; cerebral syphilitic gumma should be considered in patients with positive non-specific antibodies to syphilis/specific antibodies to syphilis in serum and cerebrospinal fluid having neurological symptoms and intracranial space-occupied foci; timely diagnosed and treated patients can prognosed well.

Objective:To analyze the characteristics of peripheral blood lymphocyte subsets in patients with relapsed neuromyelitis optica spectrum disorder (NMOSD) during rituximab (RTX) treatment and to clarify the influence of these lymphocyte subsets in NMOSD relapse.Methods:The monitoring data of lymphocyte subsets (175 times) in 76 patients diagnosed as having aquaporin-4-immunoglobulin G (AQP4-IgG)-seropositive NMOSD during RTX treatment at Department of Neurology, General Hospital of Chinese People's Liberation Army from August 2018 to August 2023 were collected. A relapse group ( n=26) and a non-relapse group ( n=149) were divided based on states at data collection (relapse or not). Two-sample t-test or Mann-Whitney U test were used to compare the differences in RTX administration intervals and lymphocyte subsets between the 2 groups. Additionally, a point biserial correlation analysis was performed to investigate the correlations of lymphocyte subsets and RTX administration intervals with NMOSD relapse. Results:The relapse group had significantly longer RTX administration intervals (10.00 [6.73, 14.37] months vs. 7.27[6.30, 9.10] months), statistically lower percentage of CD3 -CD56 + natural killer lymphocytes (10.72% [7.06%, 15.34%) vs. 13.85% [9.42%, 20.13%]), and significantly higher CD19 + B lymphocytes (7.41% [1.18%, 15.70%] vs. 3.55% [0.38%, 8.74%]) than the non-relapse group ( P<0.05). Positive correlations were noted between RTX administration intervals and NMOSD relapse and between CD3 -D19 +B lymphocytes and NMOSD relapse ( r=0.363, P<0.001; r=0.218, P=0.004); negative correlation was noted between CD3 -CD56 + NK lymphocytes and NMOSD relapse ( r=-0.193, P=0.011). Conclusion:Extended RTX administration interval can increase NMOSD relapse; CD3 -CD56 + natural killer lymphocytes and CD19 +B lymphocytes may regulate the disease states of NMOSD patients.

Objective:To evaluate and screen the regimens of tigecycline intraventricular injection in extensively drug resistant Acinetobacter baumannii (XDRAB) intracranial infection based on Monte Carlo simulation and pharmacokinetic/pharmacodynamic (PK/PD) model.Methods:Nine patients with XDRAB intracranial infection confirmed as having susceptibility to tigecycline or polymyxin antimicrobials from January 1, 2018 to December 31, 2023 were screened from electronic medical record system in Second Affiliated Hospital of Shandong First Medical University. WHONET software was used to extract pathogen susceptibility data isolated from cerebrospinal fluid samples. Minimum inhibitory concentration (MIC) of tigecycline against XDRAB was analyzed by drug susceptibility test; different regimens for intraventricular tigecycline injection were designed based on MIC: 2 mg/12 h, 3 mg/12 h, 4 mg/12 h, 5 mg/12 h, 6 mg/12 h, and 10 mg/12 h, with drug concentration of 0.5 mg/mL or 1.0 mg/mL once a day. Target value of PK/PD index was set as ?C max/MIC≥8; Monte Carlo was used to simulate the compliance of PK/PD index of tigecycline with different MIC against XDRAB for different dosed regimens (probability of target attainment [PTA] and cumulative fraction of response [CFR]); the best regiment was selected (screening basis: PTA≥90% or CFR≥90%). Results:(1) A total of 27 strains of pathogenic bacteria from 9 patients were extracted from drug susceptibility test, in which MIC of tigecycline against XDRAB was 55.56% for 2 mg/L, 25.93% for 4 mg/L, and 18.52% for 8 mg/L. (2) When the drug concentration was 0.5 mg/mL or 1.0 mg/mL, respectively, all 6 regimens had PTA>90% at 2 mg/L MIC; 5 regimens, except for 2 mg/12 h, had PTA>90% at 4 mg/L MIC; regimens of 5 mg/12 h, 6 mg/12 h, and 10 mg/12 h could achieve PTA>90% at 8 mg/L MIC. (3) When the drug concentration was 0.5 mg/mL, regimens of 4 mg/12 h, 5 mg/12 h, 6 mg/12 h, and 10 mg/12 h could achieve CFR>90%; when the drug concentration was 1 mg/mL, regimens of 4 mg/12 h, 5 mg/12 h, 6 mg/12 h, and 10 mg/12 h could achieve CFR>92%.Conclusion:In intraventricular tigecycline injection for XDRAB intracranial infection, 2 mg/12 h regimen is available in 2 mg/L MIC, 3 mg/12 h regimen is available in 4 mg/L MIC, and 5 mg/12 h regimen is available in 8 mg/L MIC, with either 0.5 mg/mL or 1 mg/mL concentration.

Objective:To explore the efficacy of cerebral vasospasm model established by brief double blood injection in cisternal cisteria.Methods:Twenty-five SD rats were randomly divided into sham-operated group, group of 1 d after subarachnoid hemorrhage (SAH), group of 3 d after SAH, group of 5 d after SAH, and group of 7 d after SAH ( n=5). Autologous blood (0.2 mL, obtained by caudal artery puncture) was directly injected into the atlanto-occipital membrane and repeated 48 h after that to establish cerebral vasospasm model. Neurological impairment was evaluated by modified Neurological Severity Score (mNSS). Diameter and cross-sectional area of the basilar artery (BA) were detected by HE staining. Differences of body mass before modeling, body mass between the 2 blood injections, mNSS scores, and diameter and cross-sectional area of BA were compared among groups. Results:(1) Body mass before modeling was not significantly different among the 5 groups ( P>0.05); differences of body mass between the 2 blood injections in the group of 1 d after SAH, group of 3 d after SAH, group of 5 d after SAH, and group of 7 d after SAH were significantly greater than those in the sham-operated group ( P<0.05). (2) The mNSS scores in the group of 1 d after SAH, group of 3 d after SAH, group of 5 d after SAH, and group of 7 d after SAH were significantly higher than those in the sham-operated group ( P<0.05). (3) BA diameter in the group of 3 d after SAH and group of 7 d after SAH was significantly shorter than that in the sham-operated group, and that in the group of 7 d after SAH was significantly shorter than that in the group of 1 d after SAH and group of 5 d after SAH ( P<0.05). BA cross-sectional area in the group of 1 d after SAH, group of 3 d after SAH, group of 5 d after SAH and group of 7 d after SAH was significantly smaller than that in the sham-operated group, and that in the group of 7 d after SAH was significantly smaller than that in the group of 1 d after SAH, group of 3 d after SAH and group of 5 d after SAH ( P<0.05). Conclusion:Compared with other traditional models, cerebral vasospasm model established by brief double blood injection in cisternal cisteria has advantages of simplified operation, short modeling time, and minimal invasion; model of 7 d after autologous blood injection enjoys optimal.

Objective:To summarize the experience of brain death determination under veno-arterial extracorporeal membrane oxygenation (VA-ECMO) assisted circulatory support, especially apnea test (AT) precautions, and to provide references for brain death determination in this scenario.Methods:In 78 patients who had VA-ECMO at Organ Transplant Center, Zhengzhou People's Hospital from October 2019 to December 2023, 8 organ donors had brain death determination under VA-ECMO assisted circulatory support. Baseline data, clinical data, and VA-ECMO data during AT trial were collected from these 8 patients to summarize the process of brain death determination.Results:Six of the 8 donors met the criteria of brain death; 10 EEG, 12 evoked potentials and 15 ATs were performed. Complications in ATs, including hypotension, decreased oxygenation and arrhythmia, were alleviated after timely improved VA-ECMO flow and applied cardiotonic and pressor drugs.Conclusion:AT is key for successful brain death determination in organ donors under VA-ECMO assisted circulatory support; therefore, complications should be closely monitored and managed.