IntroductionCognitive impairment is the main clinical manifestation of cerebral small vessel disease (CSVD). However, the mechanism and structural damage in different domains of cognitive disorders are poorly understood. There is an urgent need to quantify the relation between diffusion tensor imaging (DTI) data and impaired cognitive testing in CSVD, which may help to find biomarkers for early diagnosis or treatment evaluation. We aim to summarise the understanding of association between DTI findings and domain-specific cognitive impairment.Methods and analysisPubMed, EMBASE, Web of science, Cochrane library, Chinese National Knowledge Infrastructure Databases, Wanfang, SinoMed and VIP will be searched, from 1 January 1994 to 1 August 2021. The ClinicalTrials.gov and Chictr.org.cn records will also be searched to identify further potential studies. The included studies should report fractional anisotropy and/or and mean diffusivity/apparent diffusion coefficient data for one or more individual regions of interest in DTI analysis. Meanwhile, cognitive testing scores are also needed. This systematic review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The quality of cohort or case–control studies will be evaluated by the Newcastle-Ottawa Scale, and the cross-section studies will be evaluated by Agency for Healthcare Research and Quality scale. Meta-analysis, subgroup and sensitivity analyses, and publication bias will be all performed with Stata.Ethics and disseminationPatients and the public will not be involved in this study. The existing data from published studies will be used. The findings from this research will be relevant information regarding the association of DTI metrics with cognitive disorder, which will be published in a peer-reviewed journal. If we need to amend this protocol, we will give the date of each amendment, describe the change and give the rationale. Changes will not be incorporated into the protocol.PROSPERO registration numberCRD42021226133.
Objective K + -Cl − cotransporter-2 (KCC2), which primarily extrudes chloride in mature neurons, triggers hemiplegia limb spasticity after ischemic stroke by affecting neuronal excitability. Our previous study revealed that the Chinese herb Baishaoluoshi Decoction decreases hemiplegia limb spasticity in poststroke spasticity (PSS) patients. This study aimed at elucidating on the effects of Baishaoluoshi Decoction on the BDNF/TrKB-KCC2 pathway in PSS rat models.Methods Middle cerebral artery occlusion (MCAO) was adopted for the establishment of PSS rat models. Muscle tension was evaluated by Modified Ashworth Scale. Nissl staining and transmission electron microscopy were used to measure the protective effects of Baishaoluoshi Decoction on ischemic injury-induced neuronal damage due to MCAO. Expression levels of BDNF, TrKB, and KCC2 in brain tissues around the infarct and brainstem were detected by immunohistochemical staining. ResultsIt was found that Baishaoluoshi Decoction suppressed hemiplegia limb spasticity and alleviated the damage in neurons and synapses in PSS rat models. Importantly, the expression of BDNF, TrKB, and KCC2 in brain tissues around the infarct and brainstem were significantly upregulated after treatment with low-dose and high-dose Baishaoluoshi Decoction. Conclusion Suppression of spasticity by BaishaoluoshiDecoction in PSS rat models may be correlated with upregulated BDNF/TrKB-KCC2 pathway, which may be a complementary therapeutic strategy for PSS. NeuroReport 32: 1183
Background. The motor symptoms in patients with Parkinson's disease (PD) are commonly preceded by gastrointestinal (GI) symptoms. The enteric nervous system (ENS) has also been reported to exhibit neuropathological characteristics of PD. Objectives.To evaluate the relationship between the incidence of parkinsonism and alteration in gut microbiota and pathogens. Materials and methods.Studies in different languages that evaluate the relationship between gut microorganisms and PD were included into this meta-analysis. The outcomes of these studies were analyzed using a random effects model; it was also used to calculate the mean difference (MD) with 95% confidence interval (95% CI) in order to quantify the impact of different rehabilitation techniques on clinical parameters. Dichotomous and continuous models were used for the analysis of extracted data. Results.A total of 28 studies were included in our analysis. The analysis of small intestinal bacterial overgrowth showed a significant correlation with Parkinson's subjects compared with controls (p < 0.001). In addition, the presence of Helicobacter pylori (HP) infection was significantly related to the Parkinson's group (p < 0.001). On the other hand, there was a significantly higher abundance level of Bifidobacteriaceae (p = 0.008), Verrucomicrobiaceae (p < 0.001) and Christensenellaceae (p = 0.003) in Parkinson's subjects. In contrast, a significantly lower abundance levels in Parkinson's subjects were found in Faecalibacterium (p = 0.03), Lachnospiraceae (p = 0.005) and Prevotellaceae (p = 0.005). No significant difference was related to Ruminococcaceae. Conclusion.Parkinson's subjects showed a higher degree of alteration of gut microbiota and pathogens compared with normal human subjects. Future multicenter randomized trials are needed.
Background: Post-stroke spasticity (PSS) is a major cause of disability leading to severely impaired upper-limb flexibility and ability to walk and move, significantly affecting the quality of life of cerebral infarction patients. There is currently no recognized effective therapy. Alternatively, Chinese traditional medicine has shown promise for PSS treatment. In this regard, the BSLSF has been reported to be effective; however, its underlying mechanism remains unclear. Objective: To clarify the main targets and pathways of Baishao Luoshi Formula (BSLSF) during PSS treatment, laying the foundation for further research on its pharmacological effects. Method: In this study, network pharmacology and experimental verification were conducted to explore the potential mechanism of BSLSF systematically. After obtaining active ingredients of BSLSF from the TCMSP database, SwissTarget-Prediction and PharMapper were used to uncover BSLSF targets. PSS-related targets were gathered with GeneCards and Online Mendelian Inheritance in Man. The differentially expressed genes between BSLSF and PSS were identified by a Venn plot. The drug-active ingredient-target interaction network and Protein-protein interaction (PPI) were constructed using Cytoscape and further analyzed using the MCC algorithm of CytoHubba plugin.Then, Pathway enrichment and GO biological process enrichment analyses were performed. Subsequently, a mice model of middle cerebral artery occlusion (MCAO) was established for the in vivo experiments. Result: We found that AKT1, TNF, CASP3, VEGFA, and CREB1 were potential targets during PSS treatment. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that the mechanism of PSS was closely related to synaptic plasticity. And the immunohistochemical staining showed that BSLSF protected against ischemic stroke via the CCR5/CREB signaling pathway and probably affected synaptic plasticity. Conclusion: our study validated that treatment with BSLSF protected against ischemic stroke via the CCR5/CREB signaling pathway and could affect synaptic plasticity. In a sense, this study provides the basis for further extensive and in-depth analysis of BSLSF, enabling the quest for new drug targets at the same time.
Background: Vascular cognitive impairment (VCI) is one of the most common diseases among the elderly. However, few effective drugs have been approved for VCI. Traditional Chinese medicine (TCM) has been used in dementia for thousands of years. Currently, there is limited high-quality evidence for the efficacy of TCM, and the specific characteristics of its effects and the appropriate patient populations for TCM therapies remain unclear. Herein, we aim to explore the effectiveness and safety of TCM by conducting a longitudinal, patient-centered study. Methods: REgistry for Vascular cognitive Impairment trEatment With Traditional Chinese Medicine (REVIEW-TCM) is a prospective, observational disease registry study. 1000 VCI patients at the Hunan Hospital of Integrated Traditional Chinese and Western Medicine will be recruited based on the following criteria: aged 18 years or older, Montreal Cognitive Assessment (MoCA) score <26, and Hachinski Ischemic Score (HIS)≥7. There is no strict limit on the intervention, and different TCM formulas will be focused. Cognition, activity of daily living, quality of life, mental, psychology, ZHENG of TCM, and burden of caregiver will be evaluated at admission, and 6, 12, 18, and 24 months. Meanwhile, biological tests and neuroimaging examination will be applied to further explore the mechanism of TCM. Especially, a mixed-methods embedded design will be applied by adopting quantitative and qualitative studies to explore patients-reported outcomes of TCM. Finally, propensity score matching will be adopted to analyze the effectiveness of TCM. Discussion: To the best of our knowledge, the REVIEW-TCM study is the first comprehensive, prospective, mixed-methods, registry-based study to evaluate TCM treatment in VCI, which will analyze the effectiveness and safety of TCM in the real world and explore population characteristics and subtypes of VCI suitable for TCM. Study registration: This study was registered on www.chictr.org.cn (ChiCTR2200064756).
Objectives. Acupoint catgut embedding therapy has shown effectiveness in treating functional constipation; however, relevant, high-quality clinical evidence is scarce. This study aimed to systematically assess the effectiveness and safety of acupoint catgut embedding in treating poststroke constipation. Methods. Correlative randomized controlled trials were identified through a comprehensive literature search of PubMed, Cochrane Library/Cochrane Central Register of Controlled Trials, Web of Science, Embase, China National Knowledge Internet, Chinese Biomedical Literature Database, Wanfang, and VIP databases from inception until February 2022. Meta-analysis was performed using RevMan 5.3 software. Results. Fifteen trials involving 1084 patients were identified. The meta-analysis revealed that the acupoint catgut embedding group was significantly superior to the non-catgut embedding group with regard to the efficacy rate (RR = 1.27, 95% CI (1.19, 1.37), P < 0.05 ), the first defecation time (MD = −3.08, 95% CI (−4.53, −1.63), P < 0.05 ), the defecation sensation score (MD = −0.44, 95% CI (−0.61, −0.26), P < 0.05 ), the degree of difficulty in defecation (MD = −0.73, 95% CI (−1.10, −0.37), P < 0.05 ), the PAC-QOL scale score (MD = −10.06, 95% CI (−13.47, −6.64), P < 0.05 ), and the symptom integral (MD = −3.15, 95% CI (−3.60, −2.71), P < 0.05 ). However, there was no significant difference in the stool property score (MD = 0.06, 95% CI (−0.39, 0.50), P > 0.05 ) as well as the incidence of adverse reactions (RD = 0.01, 95% CI (−0.01, 0.03), P > 0.05 ) between the two groups. Conclusions. The results showed that acupoint catgut embedding is probably an effective and safe acupuncture treatment strategy for poststroke constipation. Nevertheless, more rigorously designed, standardized, large-sample, and multicenter randomized controlled designs are warranted to further verify the findings of this study.
ObjectiveTo investigate the association between diffusion tensor imaging (DTI) findings and domain-specific cognitive impairment in cerebral small vessel disease (CSVD).MethodsDatabases such as PubMed, Excerpta Medical Database (EMBASE), Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure Databases (CNKI), Wanfang, Chinese Biomedical Literature Database (SinoMed), and Chongqing Chinese Science and Technology Periodical Database (VIP) were comprehensively retrieved for studies that reported correlation coefficients between cognition and DTI values. Random effects models and meta-regression were applied to account for heterogeneity among study results. Subgroup and publication bias analyses were performed using Stata software.ResultsSeventy-seven studies involving 6,558 participants were included in our meta-analysis. The diagnosis classification included CSVD, white matter hyperintensities (WMH), subcortical ischemic vascular disease, cerebral microbleeding, cerebral amyloid angiopathy (CAA), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and Fabry disease. The pooled estimates showed that the fractional anisotropy (FA)-overall exhibited a moderate correlation with general cognition, executive function, attention, construction, and motor performance (r = 0.451, 0.339, 0.410, and 0.319), and the mean diffusitivity/apparent diffusion coefficient (MD/ADC)-overall was moderately associated with general cognition, executive function, and memory (r = −0.388, −0.332, and −0.303, respectively; ps < 0.05). Moreover, FA in cingulate gyrus (CG), cerebral peduncle (CP), corona radiata (CR), external capsule (EC), frontal lobe (FL), fornix (FOR), internal capsule (IC), and thalamic radiation (TR) was strongly correlated with general cognition (r = 0.591, 0.584, 0.543, 0.662, 0.614, 0.543, 0.597, and 0.571), and a strong correlation was found between MD/ADC and CG (r = −0.526), normal-appearing white matter (NAWM; r = −0.546), and whole brain white matter (WBWM; r = −0.505). FA in fronto-occipital fasciculus (FOF) (r = 0.523) and FL (r = 0.509) was strongly associated with executive function. Only MD/ADC of the corpus callosum (CC) was strongly associated with memory (r = −0.730). Besides, FA in CG (r = 0.532), CC (r = 0.538), and FL (r = 0.732) was strongly related to the attention domain. Finally, we found that the sample size, etiology, magnetic resonance imaging (MRI) magnet strength, study type, and study quality contributed to interstudy heterogeneity.ConclusionLower FA or higher MD/ADC values were related to more severe cognitive impairment. General cognition and executive function domains attracted the greatest interest. The FL was commonly examined and strongly associated with general cognition, executive function, and attention. The CC was strongly associated with memory and attention. The CG was strongly related to general cognition and attention. The CR, IC, and TR were also strongly related to general cognition. Indeed, these results should be validated in high-quality prospective studies with larger sample sizes.Systematic review registrationhttp://www.crd.york.ac.uk/PROSPERO, identifier: CRD42021226133.
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