We report a case of spinocerebellar ataxia type 8(SCA8)presenting with multisystem atrophic phenotype.The patient was a 57-year-old male with a 4-year course of illness with dizziness and ataxia as the first symptoms,followed by autonomic dysfunction and rapid eye movement sleep disorder.Neurological examination reveals autonomic dysfunction,nystagmus,dysarthria,ataxia,brain stem and cerebellar symmetrical atrophy and"hot cross bun"sign on MRI.The diagnosis of SCA8 was confirmed by the genetic testing which showed an abnormally high number of CTA/CTG repeats in the two alleles of the ATXN8OS.The patient responded well to symptomatic treatment such as ataxia and autonomic dysfunction.SCA8 is a rare movement disorder with high clinical heterogeneity.This report suggests that SCA8 can also present with autonomic dysfunction,ataxia,pontine"hot cross bun"sign and other characteristics similar to multisystem atrophy phenotype.Thus,it is necessary for clinicians to avoid misdiagnosis or missing the diagnosis of SCA8 presenting with multiple system atrophy cerebral type in clinical work.

Objective:To compare the efficacy of closed-loop target-controlled deep versus moderate neuromuscular blockade in gynecological laparoscopic surgery.Methods:This was a prospective study. Fifty American Society of Anesthesiologists Physical Status classification I or Ⅱ patients, aged 18-64 yr, with body mass index of 18-30 kg/m 2, scheduled for elective gynecological laparoscopic surgery in the General Hospital of Tianjin Medical University from March 2020 to March 2021, were allocated into 2 groups ( n=25 each) using a random number table method: closed-loop target-controlled moderate neuromuscular blockade group (group TOF) and closed-loop target-controlled deep neuromuscular blockade group (group PTC). Rocuronium was given by closed-loop target-controlled infusion in both groups. In group TOF, the target muscle relaxation was considered as train-of-four stimulation (TOF) of 1 or 2. In group PTC, the target muscle relaxation was considered as post-titanic count of 1 or 2. The score for operator′s satisfaction with muscle relaxation, grading, satisfaction rate, mean pneumo-peritoneum pressure, consumption of rocuronium, recovery index, recovery time to a TOF ratio 0.9 and time to extubation were recorded. The postoperative visual analogue scale score for abdominal pain and use of rescue analgesics were recorded, and the occurrence of complications such as shoulder pain, arm pain, nausea, vomiting and hypoxemia was also recorded within 48 h after surgery. Results:Compared with group TOF, the score for operator′s satisfaction with muscle relaxation, grading and satisfaction rate were significantly increased, the mean pneumo-peritoneum pressure was decreased, the total and average consumption of rocuronium was increased, the recovery time of a TOF ratio 0.9 was prolonged, and the postoperative visual analogue scale score for abdominal pain and usage rate of flurbiprofenate were decreased in group PTC ( P<0.05). There were no significant differences in the recovery index, tracheal extubation time or postoperative incidence of hypoxemia, shoulder pain, arm pain and nausea and vomiting between the two groups ( P>0.05). Conclusions:Compared with the closed-loop target-controlled moderate neuromuscular blockade, the closed-loop target-controlled deep neuromuscular blockade provides more satisfactory surgical conditions for gynecological laparoscopic surgery, decreases pneumoperitoneum pressure and reduces related complications, without increasing the development of postoperative adverse reactions.

Objective:To investigate the neuropsychological and imaging features of patients with posterior cortical atrophy (PCA).Methods:Patients of PCA, dementia with Lewy bodies (DLB), typical Alzheimer′s disease (t-AD) who were diagnosed in the Department of Neurology, Huashan Hospital, Fudan University from September 27, 2019, to September 24, 2021 were enrolled, and the normal controls who visited the Outpatient and Physical Examination Centers of Huashan Hospital, Fudan University and Rizhao People′s Hospital at the same time were enrolled, too. Neuropsychological assessments, magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT data of the 4-group subjects were collected. Variance analysis was used to compare the differences in neuropsychological performance among the 4 groups, and the imaging features of PCA patients were summarized.Results:Eleven PCA patients, 17 DLB patients, 31 t-AD patients, and 11 normal controls were included in the study. The cognitive function of patients in the PCA group [Mini-Mental State Examination (MMSE) score 13.52±1.81; Montreal Cognitive Assessment (MoCA) score 7.06±1.72] was significantly impaired compared to the normal control group (MMSE score 27.85±1.75, t=-6.561, P<0.001; MoCA score 23.60±1.59, t=-7.968, P<0.001]. However, there was no statistically significant difference compared to the DLB group and the t-AD group. Patients in the PCA group exhibited more severe impairments in attention, executive function, and language compared to the DLB group (Trail Making Test A score: 298.86±16.16 vs 110.07±18.62, t=9.980, P<0.001; Trail Making Test B score: 305.51±18.89 vs 230.34±23.59, t=2.865, P=0.024; Boston Naming Test score: 8.67±1.53 vs 15.66±1.56, t=-2.682, P=0.013) and the t-AD group (148.91±12.77, t=7.071, P<0.001; 200.78±19.34, t=3.789, P=0.004; 15.15±1.05, t=-2.544, P=0.016). Scores for visuospatial function [PCA group: 1(0, 1), normal control group: 3(3, 3), Z=-4.023, P<0.001] and visual perception [PCA group: 0(0, 1), normal control group: 35(34, 36), Z=-3.704, P<0.001] were significantly lower in the PCA group compared to the normal control group. The cranial MRI findings of PCA patients showed atrophy of the parietal and occipital lobes, with less obvious atrophy of the medial temporal lobe, which can be distinguished from t-AD. 18F-fluorodeoxyglucose PET/CT of the PCA patients showed a relative reduced glucose metabolism in the bilateral parietal lobe, occipital lobe and posterior cingulate gyrus, while the 18F-florbetapir PET/CT showed deposition of amyloid protein in the bilateral frontal lobe, parietal lobe, temporal lobe, and cingulate gyrus. Conclusions:PCA patients exhibit neuropsychological characteristics of visuospatial dysfunction, along with impairments in various cognitive domains such as memory, attention, and executive functions. The typical MRI feature is parietal occipital lobe atrophy, and the PET/CT findings are consistent with metabolic changes in AD.

Neuropathic pain is a chronic disease that severely afflicts the life and emotional status of patients, but currently available treatments are often ineffective. Novel therapeutic targets for the alleviation of neuropathic pain are urgently needed. Rhodojaponin VI, a grayanotoxin from Rhododendron molle, showed remarkable antinociceptive efficacy in models of neuropathic pain, but its biotargets and mechanisms are unknown. Given the reversible action of rhodojaponin VI and the narrow range over which its structure can be modified, we perforwmed thermal proteome profiling of the rat dorsal root ganglion to determine the protein target of rhodojaponin VI. N-Ethylmaleimide-sensitive fusion (NSF) was confirmed as the key target of rhodojaponin VI through biological and biophysical experiments. Functional validation showed for the first time that NSF facilitated trafficking of the Cav2.2 channel to induce an increase in Ca²⁺ current intensity, whereas rhodojaponin VI reversed the effects of NSF. In conclusion, rhodojaponin VI represents a unique class of analgesic natural products targeting Cav2.2 channels via NSF.

Objective:To explore the β-amyloid (Aβ) deposition pattern of subjects with the preclinical Alzheimer′s disease (AD), community-derived amnestic mild cognitive impairment (aMCI) and normal cognition (NC) from communities of Shanghai.Methods:According to the inclusion and exclusion criteria, 273 subjects (104 males, 169 females; age (64.2±7.6) years) were recruited from Shanghai community and memory clinics from December 2018 to July 2020. All subjects underwent MRI, 18F-AV45 PET imaging and neuropsychological scale tests and were grouped into AD, aMCI and NC groups based on clinical diagnosis. Differences in demographic information, the neuropsychological scale tests′ scores and positive rate of Aβ deposition among each group were analyzed by one-way analysis of variance or χ2 test. Aβ deposition patterns of AD and MCI groups were analyzed at voxel level, and the differences of Aβ deposition among different groups were compared. Results:Among 273 patients, the positive rates of Aβ deposition in AD, aMCI and NC groups were 84.4%(38/45), 36.4%(20/55) and 23.1%(40/173), respectively ( χ2=58.37, P<0.001). Among AD, aMCI, NC and NC (Aβ-) groups ( n=132), the education years of AD group was the lowest ((9.7±4.6) years; F=8.86, P<0.001). In addition, there were significant differences in the scores of several neuropsychological scale tests among AD, aMCI, NC groups and NC (Aβ-) group ( F values: 27.68-235.50, all P<0.001). Compared with subjects in NC(Aβ-) group, the Aβ depositions in the aMCI and AD groups were widely distributed in the whole cerebral cortex; and AD group had higher Aβ deposition in bilateral frontal, parietal, temporal, occipital lobe, cingulate gyrus and precuneus than aMCI group. Conclusions:The positive rate of Aβ deposition in the preclinical AD population from the Shanghai community is obtained. There are significant different Aβ deposition patterns in subjects at different stages of AD.

Spinocerebellar ataxia (SCA) is a group of highly heterogeneous autosomal dominant genetic disease, including many subtypes. SCA11 is a rare subtype of SCA, and is caused by mutant TTBK2 gene. A case of SCA11 was reported in this article. Whole exome sequencing showed that there was a c.1284dupA frameshift mutation in TTBK2 gene. Literature review found that only 6 pedigrees of SCA11 have been reported, but the mutation site of this case is a novel identified mutation that has not been reported in the Human Gene Mutation Database.

Objective:To investigate the clinical, neuropsychological, and neuroimage characteristics in patients with corticobasal syndrome (CBS), and to elucidate the exact diagnosis of CBS patients.Methods:Twelve CBS cases admitted to the Department of Neurology, Huashan Hosiptal,Fudan University from April 2019 to July 2021 were retrospectively enrolled in this study. Those data, including clinical features (demographic data and clinical characteristics of cortical dysfunction and movement disorder), neuropsychological assessment [Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scales score], brain magnetic resonance imaging (MRI) and multi-mode positron emission tomography (PET)/CT, were collected and carefully reviewed. Exact diagnosis of these patients was given according to the disease diagnosis criteria.Results:Cortical dysfunction and asymmetrical movement disorders were found in all cases, with poor response to levodopa. Patients suffered from cognitive impairment (MMSE score 16.16±9.82, MoCA score 13.44±7.35). The cranial MRI demonstrated significant asymmetric atrophy of frontal and parietal lobes, especially in the pre- and post-central gyrus. Fluorodeoxyglucose PET of 12 patients showed asymmetric frontal lobe and basal ganglia (especially caudate and putamen) hypometabolism (obviously on the contralateral side of the affected limb). Tau PET was implemented in 11 patients and displayed that abnormal tau protein deposition was positive in the cortex and/or subcortex in all patients. Of the 4 cases, who completed amyloid PET, amyloid protein deposition was positive in the cortex of 2 patients. As a result, 6 patients were diagnosed as progressive supranuclear palsy, 1 patient was diagnosed as corticobasal degeneration, and 5 patients were diagnosed as Alzheimer′s disease.Conclusions:The etiology of CBS is heterogeneous. The combination of clinical manifestation, cranial MRI and multi-mode PET/CT helps the differential diagnosis of CBS.

Objective:To evaluate the effects of vitamin K 2 on sevoflurane-induced cognitive decline in aged mice. Methods:A total of 72 SPF healthy female C57BL/6J mice, aged 12 months, weighing 20-25 g, were divided into 4 groups ( n=18 each) using a random number table method: control+ corn oil group (group Con+ Oil), sevoflurane+ corn oil group (group Sevo+ Oil), control+ vitamin K 2 group (group Con+ K 2) and sevoflurane+ vitamin K 2 group (group Sevo+ K 2). The mice in Sevo+ Oil and Sevo+ K 2 groups were anesthetized with 2.5% sevoflurane+ 33% oxygen for 2 h. The mice in Con+ Oil and Con+ K 2 groups were treated with 33% oxygen only.The animals in Con+ Oil and Sevo+ Oil groups were intraperitoneally injected with corn oil 100 μl at 30 min before oxygen or sevoflurane inhalation.Vitamin K 2 (dissolved in corn oil, concentration 1 mg/ml) 100 mg/kg was injected intraperitoneally in Con+ K 2 and Sevo+ K 2 groups.At 24 h after sevoflurane inhalation, 8 mice from each group were randomly selected and sacrificed, and the hippocampal tissues were removed for determination of activity of ATPase, contents of interleukin-1beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α) (by enzyme-linked immunosorbent assay) and the expression of AT8 and PHF1 (by Western blot). The remaining 10 mice in each group received standardized feeding, and the cognitive function was assessed using Y-maze at 1, 3, 5, 7 and 14 days after sevoflurane inhalation. Results:Compared with group Con+ Oil, the contents of IL-1β, IL-6 and TNF-α were significantly increased, expression of AT8 and PHF1 were up-regulated, activity of ATPase was decreased, and spontaneous alternation percentage was decreased at 1, 3, 5, 7 and 14 days after sevoflurane inhalation in group Sevo+ Oil ( P<0.05). Compared with group Sevo+ Oil, the contents of IL-1β, IL-6 and TNF-α were significantly decreased, expression of AT8 and PHF1 were down-regulated, activity of ATPase was increased, and spontaneous alternation percentage was increased at 1, 3, 5, 7 and 14 days in group Sevo+ K 2 ( P<0.05). There was no significant difference in the above indicators between group Con+ K 2 and group Sevo+ K 2 ( P>0.05). Conclusion:Vitamin K 2 can improve sevoflurane-induced cognitive decline in aged mice, the mechanism is related to increasing activity of ATPase and inhibiting the up-regulation of AT8 and PHF1 expression in hippocampus.

Objective:To evaluate the role of heme oxygenase-1 (HO-1) in sevoflurane-induced improvement in sepsis-associated encephalopathy (SAE) in mice.Methods:A total of 136 adult male mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=34 each) using a random number table method: sham operation group (group Sham), SAE group, SAE+ sevoflurane group (group SAE+ Sevo) and SAE+ sevoflurane+ HO-1 inhibitor Zn Protoporphyrin Ⅸ (ZnPPⅨ) group (group SAE+ Sevo+ ZnPPⅨ). The model of SAE was established by cecal ligation and puncture (SAE) in anesthetized mice.In SAE+ Sevo and SAE+ Sevo+ ZnPPⅨ groups, 2% sevoflurane-33% oxygen was inhaled for 2 h starting from the time point immediately after establishment of the model, while 33% oxygen was inhaled for 2 h in Sham and SAE groups.ZnPPⅨ 25 mg/kg was intraperitoneally injected at 30 min before the model was established in group SAE+ Sevo+ ZnPPⅨ.Six mice were sacrificed at 6, 12 and 24 h after establishment of the model for determination of levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), high mobility group protein B1 (HMGB1) and HO-1 in cortical tissues (by enzyme-linked immunosorbent assay) and the expression of HO-1 (by Western blot). Another 6 mice were sacrificed for determination of apoptosis in cortical tissue (by TUNEL staining), and apoptotic index (AI) was calcultated.Ten mice in each group were selected, Y maze test was performed at 3, 5, 7 and 14 days after establishment of the model, and the percentage of spontaneous alternation was calculated. Results:Compared with Sham group, the levels of TNF-α, IL-1β and HMGB1, AI, HO-1 activity and its expression level in cortex were significantly increased, and the percentage of spontaneous alternation was decreased in SAE, SAE+ Sevo and SAE+ Sevo+ ZnPPⅨ groups ( P<0.05). Compared with group SAE, the levels of TNF-α, IL-1β and HMGB1 and AI were significantly decreased, and HO-1 activity and its expression level and the percentage of spontaneous alternation were increased in group SAE+ Sevo, the levels of TNF-α, IL-1β and HMGB1 in cortex were decreased ( P<0.05), and no significant change was found in the other parameters in group SAE+ Sevo+ ZnPPⅨ ( P>0.05). Compared with group SAE+ Sevo, the levels of TNF-α, IL-1β and HMGB1 and AI were significantly increased, and HO-1 activity and its expression level and the percentage of spontaneous alternation were decreased in group SAE+ Sevo+ ZnPPⅨ ( P<0.05). Conclusion:The mechanism by which sevoflurane improves SAE is related to increasing HO-1 activity and reducing inflammatory response in cortical tissues of mice.

Functional cognitive disorder (FCD) refers to complaints of persistent problematic cognitive decline, which is inconsistent between self-reported symptoms and daily function and/or neuropsychological test results, and the symptoms lasted for at least six months without obvious progress. Poor ability to reflect on and monitor cognitive processes has been suggested as a key mechanism underlying the disorder. In this review, the concept, research status, clinical manifestations and diagnosis of FCD were systematically examined, which is helpful to identify the subjective cognitive decline caused by non-degenerative diseases and conduct individualized intervention treatment.