Rhodojaponin VI indirectly targets Cav2.2 channels via N-ethylmaleimide-sensitive fusion protein to alleviate neuropathic pain

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.

Imaging study of β-amyloid deposits in preclinical Alzheimer′s disease patients in communities of Shanghai / 中华核医学与分子影像杂志

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.

Characteristics of clinical and neuroimage findings in patients with corticobasal syndrome / 中华神经科杂志

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.

Spinocerebellar ataxia type 11: a case report / 中华神经科杂志

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.

Progress of functional cognitive disorder / 中华神经科杂志

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.

Investigation and analysis on the usage of mobile phone sports software in CDC staffs and its impact on their health / 中国职业医学

OBJECTIVE: To study the use of mobile phone sports software by the staffs of Centers for Disease Control( CDC)and its impact on their health. METHODS: Using cluster random sampling method,291 staff members of CDC in 7 prefecture-level cities in Hunan Province were selected as research subjects. The self-designed questionnaire was used to investigate the use of mobile phone sports software,and the Sub-Health Scale was used to investigate their health status.The impact of mobile phone sports software on their health was analyzed. RESULTS: The usage rate of mobile phone sports software was 28. 5%(83/291). The utilization rate of mobile phone sports software in postgraduate staffs was higher than that of undergraduates,college graduates and those with less than bachelor's degree( P < 0. 01). The usage rate of mobile exercise software of the CDC staff whose BMI was 18. 5 ~ kg/m~2 was lower than those whose BMI was 24. 0 ~ or 28. 0 ~kg/m~2(P < 0. 001). The sub-health incidence rate in those who used mobile sports software was lower than those who did not( P < 0. 05). The incidences of feeling fatigue,dizziness,lack of attention,upset,more dream,insomnia,poor memory in CDC staffs who used mobile phone sports software were lower than those who did not( P < 0. 05). CONCLUSION: The use of mobile phone sports software has positive effect on health promotion in CDC staffs.

The 4 year follow-up investigation of cognitive function in patients after acute stroke / 中华老年医学杂志

Objective To investigate the 4-year follow up of cognitive function outcomes and characteristics in patients after stroke.Methods Sixty three cases according with the diagnostic standard of acute unifocal subcortical stroke were consecutively collected in neurological ward from December 2009 to November 2010.They were followed up for average four years.Forty one out of them completed the neuropsychology tests identical to the baseline,which covered the general cognition function,attention,execution,memory,language,spatial,etc.According to the standard of clinical diagnosis,cognition function is divided into five degrees,including normal,VCI-ND,mild VaD,moderate VaD,and severe VaD.The improved group had 13 cases whose cognition function was improved by one or more ranks.The progressive group had 12 cases whose cognition function progressed by one or more ranks.The stable group had 16 cases whose cognition function remained the same as the baseline.Results According to qualitative analysis on the baseline versus 4-year follow-up outcome,in 13 improved cases,8 were VCI-ND and 5 were mild VaD.In 16 stable cases,11 were normal,4 were VCI-ND and 1 was mild VaD.In 12 progressive cases,3 were normal (change to mild VaD after follow-up),5 were VCI-ND (change to mild and moderate VaD after follow-up) and 4 were mild VaD (change to moderate VaD after 4-year follow-up).In the comparison of baseline cognition function among the improved,progressive and stable group,there was only one significantly different score (the right number of SCWT-A) in the improved and progressive group.The cognition function of improved group had significant differences in CFT-copy,right number of SCWT-C and the time of TMT-B before versus after follow-up.The cognition function of progressive group had significant differences in AVLT-Delay Recall and CFT-Recall.Conclusion Long-term cognitive function outcome after stroke is heterogenetic.The location of cognitive impairment or progression is not the same model for different cognitive outcome group.