Effects of individual metabolic brain network changes co-affected by T2DM and aging on the probabilities of T2DM: protective and risk factors.

Neuroimaging markers for risk and protective factors related to type 2 diabetes mellitus are critical for clinical prevention and intervention. In this work, the individual metabolic brain networks were constructed with Jensen-Shannon divergence for 4 groups (elderly type 2 diabetes mellitus and healthy controls, and middle-aged type 2 diabetes mellitus and healthy controls). Regional network properties were used to identify hub regions. Rich-club, feeder, and local connections were subsequently obtained, intergroup differences in connections and correlations between them and age (or fasting plasma glucose) were analyzed. Multinomial logistic regression was performed to explore effects of network changes on the probability of type 2 diabetes mellitus. The elderly had increased rich-club and feeder connections, and decreased local connection than the middle-aged among type 2 diabetes mellitus; type 2 diabetes mellitus had decreased rich-club and feeder connections than healthy controls. Protective factors including glucose metabolism in triangle part of inferior frontal gyrus, metabolic connectivity between triangle of the inferior frontal gyrus and anterior cingulate cortex, degree centrality of putamen, and risk factors including metabolic connectivities between triangle of the inferior frontal gyrus and Heschl's gyri were identified for the probability of type 2 diabetes mellitus. Metabolic interactions among critical brain regions increased in type 2 diabetes mellitus with aging. Individual metabolic network changes co-affected by type 2 diabetes mellitus and aging were identified as protective and risk factors for the likelihood of type 2 diabetes mellitus, providing guiding evidence for clinical interventions.

White matter fiber integrity and structural brain network topology: implications for balance function in postischemic stroke patients.

Previous studies have suggested that ischemic stroke can result in white matter fiber injury and modifications in the structural brain network. However, the relationship with balance function scores remains insufficiently explored. Therefore, this study aims to explore the alterations in the microstructural properties of brain white matter and the topological characteristics of the structural brain network in postischemic stroke patients and their potential correlations with balance function. We enrolled 21 postischemic stroke patients and 21 age, sex, and education-matched healthy controls (HC). All participants underwent balance function assessment and brain diffusion tensor imaging. Tract-based spatial statistics (TBSS) were used to compare the fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity of white matter fibers between the two groups. The white matter structural brain network was constructed based on the automated anatomical labeling atlas, and we conducted a graph theory-based analysis of its topological properties, including global network properties and local node properties. Additionally, the correlation between the significant structural differences and balance function score was analyzed. The TBSS results showed that in comparison to the HC, postischemic stroke patients exhibited extensive damage to their whole-brain white matter fiber tracts (P < 0.05). Graph theory analysis showed that in comparison to the HC, postischemic stroke patients exhibited statistically significant reductions in the values of global efficiency, local efficiency, and clustering coefficient, as well as an increase in characteristic path length (P < 0.05). In addition, the degree centrality and nodal efficiency of some nodes in postischemic stroke patients were significantly reduced (P < 0.05). The white matter fibers of the entire brain in postischemic stroke patients are extensively damaged, and the topological properties of the structural brain network are altered, which are closely related to balance function. This study is helpful in further understanding the neural mechanism of balance function after ischemic stroke from the white matter fiber and structural brain network topological properties.

Circuit-based neuromodulation enhances delayed recall in amnestic mild cognitive impairment.

BACKGROUND: This study aimed to investigate the efficacy of circuits-based paired associative stimulation (PAS) in adults with amnestic mild cognitive impairment (aMCI). METHODS: We conducted a parallel-group, randomised, controlled clinical trial. Initially, a cohort of healthy subjects was recruited to establish the cortical-hippocampal circuits by tracking white matter fibre connections using diffusion tensor imaging. Subsequently, patients diagnosed with aMCI, matched for age and education, were randomly allocated in a 1:1 ratio to undergo a 2-week intervention, either circuit-based PAS or sham PAS. Additionally, we explored the relationship between changes in cognitive performance and the functional connectivity (FC) of cortical-hippocampal circuits. RESULTS: FCs between hippocampus and precuneus and between hippocampus and superior frontal gyrus (orbital part) were most closely associated with the Auditory Verbal Learning Test (AVLT)_N5 score in 42 aMCI patients, thus designated as target circuits. The AVLT_N5 score improved from 2.43 (1.43) to 5.29 (1.98) in the circuit-based PAS group, compared with 2.52 (1.44) to 3.86 (2.39) in the sham PAS group (p=0.003; Cohen's d=0.97). A significant decrease was noted in FC between the left hippocampus and left precuneus in the circuit-based PAS group from baseline to postintervention (p=0.013). Using a generalised linear model, significant group×FC interaction effects for the improvements in AVLT_N5 scores were found within the circuit-based PAS group (B=3.4, p=0.017). CONCLUSIONS: Circuit-based PAS effectively enhances long-term delayed recall in adults diagnosed with aMCI, which includes individuals aged 50-80 years. This enhancement is potentially linked to the decreased functional connectivity between the left hippocampus and left precuneus. TRIAL REGISTRATION NUMBER: ChiCTR2100053315; Chinese Clinical Trial Registry.

Comparative efficacy of different noninvasive brain stimulation protocols on upper-extremity motor function and activities of daily living after stroke: a systematic review and network meta-analysis.

The objectives of the study were to systematically evaluate the rehabilitation effect of noninvasive brain stimulation (NIBS) on upper extremity motor function and activities of daily living in stroke patients and to prioritize various stimulation protocols for reliable evidence-based medical recommendations in patients with upper extremity motor dysfunction after stroke. Web of Science, PubMed, Embase, Cochrane Library, CNKI, Wanfang, VIP, and CBM were searched to collect all randomized controlled trials (RCTs) of NIBS to improve upper extremity motor function in stroke patients. The retrieval time was from the establishment of all databases to May 2023. According to the Cochrane system evaluation manual, the quality of the included studies was evaluated, and the data were extracted. Statistical analysis was carried out by using RevMan 5.3, R 4.3.0, and Stata 17.0 software. Finally, 94 RCTs were included, with a total of 5546 patients. Meta-analysis showed that NIBS improved the Fugl-Meyer assessment (FMA) score (mean difference (MD) = 6.51, 95% CI 6.20 ~ 6.82, P < 0.05), MBI score (MD = 7.69, 95% CI 6.57 ~ 8.81, P < 0.05), ARAT score (MD = 5.06, 95% CI 3.85 ~ 6.27, P < 0.05), and motor evoked potential (MEP) amplitude. The modified Ashworth scale score (MD = - 0.37, 95% CI - 0.60 to - 0.14, P < 0.05), National Institutes of Health Stroke Scale score (MD = - 2.17, 95% CI - 3.32 to - 1.11, P < 0.05), incubation period of MEP (MD = - 0.72, 95% CI - 1.06 to - 0.38, P < 0.05), and central motor conduction time (MD = - 0.90, 95% CI - 1.29 to - 0.50, P < 0.05) were decreased in stroke patients. Network meta-analysis showed that the order of interventions in improving FMA scores from high to low was anodal-transcranial direct current stimulation (tDCS) (surface under the cumulative ranking curve (SUCRA) = 83.7%) > cathodal-tDCS (SUCRA = 80.2%) > high-frequency (HF)-repetitive transcranial magnetic stimulation (rTMS) (SUCRA = 68.5%) > low-frequency (LF)-rTMS (SUCRA = 66.5%) > continuous theta burst stimulation (cTBS) (SUCRA = 54.2%) > bilateral-tDCS (SUCRA = 45.2%) > intermittent theta burst stimulation (iTBS) (SUCRA = 34.1%) > sham-NIBS (SUCRA = 16.0%) > CR (SUCRA = 1.6%). In terms of improving MBI scores, the order from high to low was anodal-tDCS (SUCRA = 88.7%) > cathodal-tDCS (SUCRA = 85.4%) > HF-rTMS (SUCRA = 63.4%) > bilateral-tDCS (SUCRA = 56.0%) > LF-rTMS (SUCRA = 54.2%) > iTBS (SUCRA = 32.4%) > sham-NIBS (SUCRA = 13.8%) > CR (SUCRA = 6.1%). NIBS can effectively improve upper extremity motor function and activities of daily living after stroke. Among the various NIBS protocols, anodal-tDCS demonstrated the most significant intervention effect, followed by cathodal-tDCS and HF-rTMS.

Motor imagery-based brain-computer interface rehabilitation programs enhance upper extremity performance and cortical activation in stroke patients.

BACKGROUND: The most challenging aspect of rehabilitation is the repurposing of residual functional plasticity in stroke patients. To achieve this, numerous plasticity-based clinical rehabilitation programs have been developed. This study aimed to investigate the effects of motor imagery (MI)-based brain-computer interface (BCI) rehabilitation programs on upper extremity hand function in patients with chronic hemiplegia. DESIGN: A 2010 Consolidated Standards for Test Reports (CONSORT)-compliant randomized controlled trial. METHODS: Forty-six eligible stroke patients with upper limb motor dysfunction participated in the study, six of whom dropped out. The patients were randomly divided into a BCI group and a control group. The BCI group received BCI therapy and conventional rehabilitation therapy, while the control group received conventional rehabilitation only. The Fugl-Meyer Assessment of the Upper Extremity (FMA-UE) score was used as the primary outcome to evaluate upper extremity motor function. Additionally, functional magnetic resonance imaging (fMRI) scans were performed on all patients before and after treatment, in both the resting and task states. We measured the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), z conversion of ALFF (zALFF), and z conversion of ReHo (ReHo) in the resting state. The task state was divided into four tasks: left-hand grasping, right-hand grasping, imagining left-hand grasping, and imagining right-hand grasping. Finally, meaningful differences were assessed using correlation analysis of the clinical assessments and functional measures. RESULTS: A total of 40 patients completed the study, 20 in the BCI group and 20 in the control group. Task-related blood-oxygen-level-dependent (BOLD) analysis showed that when performing the motor grasping task with the affected hand, the BCI group exhibited significant activation in the ipsilateral middle cingulate gyrus, precuneus, inferior parietal gyrus, postcentral gyrus, middle frontal gyrus, superior temporal gyrus, and contralateral middle cingulate gyrus. When imagining a grasping task with the affected hand, the BCI group exhibited greater activation in the ipsilateral superior frontal gyrus (medial) and middle frontal gyrus after treatment. However, the activation of the contralateral superior frontal gyrus decreased in the BCI group relative to the control group. Resting-state fMRI revealed increased zALFF in multiple cerebral regions, including the contralateral precentral gyrus and calcarine and the ipsilateral middle occipital gyrus and cuneus, and decreased zALFF in the ipsilateral superior temporal gyrus in the BCI group relative to the control group. Increased zReHo in the ipsilateral cuneus and contralateral calcarine and decreased zReHo in the contralateral middle temporal gyrus, temporal pole, and superior temporal gyrus were observed post-intervention. According to the subsequent correlation analysis, the increase in the FMA-UE score showed a positive correlation with the mean zALFF of the contralateral precentral gyrus (r = 0.425, P < 0.05), the mean zReHo of the right cuneus (r = 0.399, P < 0.05). CONCLUSION: In conclusion, BCI therapy is effective and safe for arm rehabilitation after severe poststroke hemiparesis. The correlation of the zALFF of the contralateral precentral gyrus and the zReHo of the ipsilateral cuneus with motor improvements suggested that these values can be used as prognostic measures for BCI-based stroke rehabilitation. We found that motor function was related to visual and spatial processing, suggesting potential avenues for refining treatment strategies for stroke patients. TRIAL REGISTRATION: The trial is registered in the Chinese Clinical Trial Registry (number ChiCTR2000034848, registered July 21, 2020).

Morphological alterations of contralesional hemisphere relate to functional outcomes after stroke.

The present study aimed to investigate poststroke morphological alterations contralesionally and correlations with functional outcomes. Structural magnetic resonance images were obtained from 27 poststroke patients (24 males, 50.21 ± 10.97 years) and 20 healthy controls (13 males, 46.63 ± 12.18 years). Voxel-based and surface-based morphometry analysis were conducted to detect alterations of contralesional grey matter volume (GMV), cortical thickness (CT), gyrification index (GI), sulcus depth (SD), and fractal dimension (FD) in poststroke patients. Partial correlation analysis was used to explore the relationship between regions with significant structural differences and scores of clinical assessments, including Modified Barthel Index (MBI), Berg Balance Scale (BBS), Fugl-Meyer Assessment of Upper Extremity (FMA-UE), Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA). Correction for multiplicity was conducted within each parameter and for all tests. GMV significantly decreased in the contralesional motor-related, occipital and temporal cortex, limbic system, and cerebellum lobe (P < 0.01, family-wise error [FWE] correction). Lower CT was found in the contralesional precentral and lingual gyrus (P < 0.01, FWE correction), while lower GI found in the contralesional superior temporal gyrus and insula (P < 0.01, FWE correction). There were significant correlations between GMV of contralesional lingual gyrus and MBI (P = 0.031, r = 0.441), and BBS (P = 0.047, r = 0.409) scores, and GMV of contralesional hippocampus and FMA-UE scores (P = 0.048, r = 0.408). In conclusion, stroke patients exhibited wide grey matter loss and cortical morphological changes in the contralesional hemisphere, which correlated with sensorimotor functions and the ability of daily living.

Effects of cortico-cortical paired associative stimulation based on multisensory integration to brain network connectivity in stroke patients: study protocol for a randomized doubled blind clinical trial.

INTRODUCTION: Brain has a spontaneous recovery after stroke, reflecting the plasticity of the brain. Currently, TMS is used for studies of single-target brain region modulation, which lacks consideration of brain networks and functional connectivity. Cortico-cortical paired associative stimulation (ccPAS) promotes recovery of motor function. Multisensory effects in primary visual cortex(V1) directly influence behavior and perception, which facilitate motor functional recovery in stroke patients. Therefore, in this study, dual-targeted precise stimulation of V1 and primary motor cortex(M1) on the affected hemisphere of stroke patients will be used for cortical visuomotor multisensory integration to improve motor function. METHOD: This study is a randomized, double-blind controlled clinical trial over a 14-week period. 69 stroke subjects will be enrolled and divided into sham stimulation group, ccPAS low frequency group, and ccPAS high frequency group. All groups will receive conventional rehabilitation. The intervention lasted for two weeks, five times a week. Assessments will be performed before the intervention, at the end of the intervention, and followed up at 6 and 14 weeks. The primary assessment indicator is the 'Fugl-Meyer Assessment of the Upper Extremity ', secondary outcomes were 'The line bisection test', 'Modified Taylor Complex Figure', 'NIHSS' and neuroimaging assessments. All adverse events will be recorded. DISCUSSION: Currently, ccPAS is used for the modulation of neural circuits. Based on spike-timing dependent plasticity theory, we can precisely intervene in the connections between different cortices to promote the recovery of functional connectivity on damaged brain networks after stroke. We hope to achieve the modulation of cortical visuomotor interaction by combining ccPAS with the concept of multisensory integration. We will further analyze the correlation between analyzing visual and motor circuits and explore the alteration of neuroplasticity by the interactions between different brain networks. This study will provide us with a new clinical treatment strategy to achieve precise rehabilitation for patient with motor dysfunction after stroke. TRIAL REGISTRATION: This trial was registered in the Chinese Clinical Trial Registry with code ChiCTR2300067422 and was approved on January 16, 2023.

Focal ischemic stroke modifies microglia-derived exosomal miRNAs: potential role of mir-212-5p in neuronal protection and functional recovery.

BACKGROUND: Ischemic stroke is a severe type of stroke with high disability and mortality rates. In recent years, microglial exosome-derived miRNAs have been shown to be promising candidates for the treatment of ischemic brain injury and exert neuroprotective effects. Mechanisms underlying miRNA dysregulation in ischemic stroke are still being explored. Here, we aimed to verify whether miRNAs derived from exosomes exert effects on functional recovery. METHODS: MiR-212-5p agomir was employed to upregulate miR-212-5p expression in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) as well as an oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro. Western blot analysis, qRT-PCR and immunofluorescence staining and other methods were applied to explore the underlying mechanisms of action of miR-212-5p. RESULTS: The results of our study found that intervention with miR-212-5p agomir effectively decreased infarct volume and restored motor function in MCAO/R rats. Mechanistically, miR-212-5p agomir significantly reduced the expression of PlexinA2 (PLXNA2). Additionally, the results obtained in vitro were similar to those achieved in vivo. CONCLUSION: In conclusion, the present study indicated that PLXNA2 may be a target gene of miR-212-5p, and miR-212-5p has great potential as a target for the treatment and diagnosis of ischemic stroke.

[Systemic lupus erythematosus associated macrophage activation syndrome with neuropsychiatric symptoms: A report of 2 cases].

Systemic lupus erythematosus (SLE) associated macrophage activation syndrome (MAS) is clinically severe, with a high mortality rate and rare neuropsychiatric symptoms. In the course of diagnosis and treatment, it is necessary to actively determine whether the neuropsychiatric symptoms in patients are caused by neuropsychiatric systemic lupus erythematosus (NPSLE) or macrophage activation syndrome. This paper retrospectively analyzed the clinical data of 2 cases of SLE associated MAS with neuropsychiatric lesions, Case 1: A 30-year-old female had obvious alopecia in 2019, accompanied by emaciation, fatigue and dry mouth. In March 2021, she felt weak legs and fell down, followed by fever and chills without obvious causes. After completing relevant examinations, she was diagnosed with SLE and given symptomatic treatments such as hormones and anti-infection, but the patient still had fever. The relevant examinations showed moderate anemia, elevated ferritin, elevated triglycerides, decreased NK cell activity, and a perforin positivity rate of 4.27%, which led to the diagnosis of "pre-hemophagocytic syndrome (HPS)". In May 2021, the patient showed mental trance and babble, and was diagnosed with "SLE-associated MAS"after completing relevant examinations. After treatment with methylprednisolone, anti-infection and psychotropic drugs, the patient's temperature was normal and mental symptoms improved. Case 2: A 30-year-old female patient developed butterfly erythema on both sides of the nose on her face and several erythema on her neck in June 2019, accompanied by alopecia, oral ulcers, and fever. She was diagnosed with "SLE" after completing relevant examinations, and her condition was relieved after treatment with methylprednisolone and human immunoglobulin. In October 2019, the patient showed apathy, no lethargy, and fever again, accompanied by dizziness and vomiting. The relevant examination indicated moderate anemia, decreased NK cell activity, elevated triglycerides, and elevated ferritin. The patient was considered to be diagnosed with "SLE, NPSLE, and SLE-associated MAS". After treatment with hormones, human immunoglobulin, anti-infection, rituximab (Mabthera), the patient's condition improved and was discharged from the hospital. After discharge, the patient regularly took methylprednisolone tablets (Medrol), and her psychiatric symptoms were still intermittent. In November 2019, she developed symptoms of fever, mania, and delirium, and later turned to an apathetic state, and was given methylprednisolone intravenous drip and olanzapine tablets (Zyprexa) orally. After the mental symptoms improved, she was treated with rituximab (Mabthera). Later, due to repeated infections, she was replaced with Belizumab (Benlysta), and she was recovered from her psychiatric anomalies in March 2021. Through the analysis of clinical symptoms, imaging examination, laboratory examination, treatment course and effect, it is speculated that the neuropsychiatric symptoms of case 1 are more likely to be caused by MAS, and that of case 2 is more likely to be caused by SLE. At present, there is no direct laboratory basis for the identification of the two neuropsychiatric symptoms. The etiology of neuropsychiatric symptoms can be determined by clinical manifestations, imaging manifestations, cerebrospinal fluid detection, and the patient's response to treatment. Early diagnosis is of great significance for guiding clinical treatment, monitoring the condition and judging the prognosis. The good prognosis of the two cases in this paper is closely related to the early diagnosis, treatment and intervention of the disease.

Effectiveness of robot-assisted virtual reality mirror therapy for upper limb motor dysfunction after stroke: study protocol for a single-center randomized controlled clinical trial.

BACKGROUND: Upper limb motor dysfunction is a common sequela of stroke, and its clinical efficacy needs to be improved. This protocol describes a trial to verify the clinical efficacy of robot-assisted virtual reality mirror therapy (RAVRMT) in improving upper limb motor dysfunction in stroke patients, and to explore the central mechanism by using functional magnetic resonance imaging (fMRI). METHODS: This trial will be a single-center, assessor-blinded, randomized controlled clinical study. Thirty-two eligible patients will be randomly divided into 2 groups according to the ratio of 1:1, namely virtual reality mirror therapy (VRMT) group and robot-assisted virtual reality mirror therapy (RAVRMT) group. The interventions will be performed once a day for 4 weeks. Primary outcome is Fugl-Meyer motor function assessment-Upper Extremity (FMA-UE), secondary outcomes are the Montreal Cognitive Assessment (MoCA), activities of daily living (ADL), quality of life (QOL), the pain visual analogue scale (VAS-pain) and fMRI. Adverse events will be recorded, and severe adverse events will be used as criteria to discontinue the intervention. DISCUSSION: Combined application of robot-assisted therapy and virtual reality mirror therapy could theoretically activate mirror neuron system and reward circuits to a greater extent, but further high-quality research is needed. The results of this trial will determine whether RAVRMT could better improve upper limb motor dysfunction after stroke and explore its central mechanism using fMRI. TRIAL REGISTRATION: This trial was prospectively registered at ClinicalTrials.gov (ChiCTR2200061721; 01 July 2022).

Autism-like behaviours and germline transmission in transgenic monkeys overexpressing MeCP2.

Methyl-CpG binding protein 2 (MeCP2) has crucial roles in transcriptional regulation and microRNA processing. Mutations in the MECP2 gene are found in 90% of patients with Rett syndrome, a severe developmental disorder with autistic phenotypes. Duplications of MECP2-containing genomic segments cause the MECP2 duplication syndrome, which shares core symptoms with autism spectrum disorders. Although Mecp2-null mice recapitulate most developmental and behavioural defects seen in patients with Rett syndrome, it has been difficult to identify autism-like behaviours in the mouse model of MeCP2 overexpression. Here we report that lentivirus-based transgenic cynomolgus monkeys (Macaca fascicularis) expressing human MeCP2 in the brain exhibit autism-like behaviours and show germline transmission of the transgene. Expression of the MECP2 transgene was confirmed by western blotting and immunostaining of brain tissues of transgenic monkeys. Genomic integration sites of the transgenes were characterized by a deep-sequencing-based method. As compared to wild-type monkeys, MECP2 transgenic monkeys exhibited a higher frequency of repetitive circular locomotion and increased stress responses, as measured by the threat-related anxiety and defensive test. The transgenic monkeys showed less interaction with wild-type monkeys within the same group, and also a reduced interaction time when paired with other transgenic monkeys in social interaction tests. The cognitive functions of the transgenic monkeys were largely normal in the Wisconsin general test apparatus, although some showed signs of stereotypic cognitive behaviours. Notably, we succeeded in generating five F1 offspring of MECP2 transgenic monkeys by intracytoplasmic sperm injection with sperm from one F0 transgenic monkey, showing germline transmission and Mendelian segregation of several MECP2 transgenes in the F1 progeny. Moreover, F1 transgenic monkeys also showed reduced social interactions when tested in pairs, as compared to wild-type monkeys of similar age. Together, these results indicate the feasibility and reliability of using genetically engineered non-human primates to study brain disorders.

Correlation between gastritis cystica profunda and the risk of lymph node metastasis in early gastric cancer.

In early gastric cancer (EGC) patients, lymph node metastasis (LNM) risk assessment is particularly important for the selection of surgical methods. In this study, we investigated the correlation between gastritis cystica profunda (GCP) and the risk of LNM in EGC. From January 2014 to December 2019, EGC patients who underwent curative radical gastrectomy were enrolled in this study. The clinicopathological features were analyzed, and the correlation between GCP and the risk of lymph node metastasis was assessed. Data for 180 EGC patients were analyzed, and 17.8% (32/180) had LNM. The incidence of LNM was 2.6% in the GCP-positive group and 21.8% in the GCP-negative group. Univariate analysis revealed that GCP, depth of tumor invasion, and lymphovascular invasion were the risk factors of LNM in EGC patients. Multiple regression analysis showed that GCP was associated with the risk of LNM in EGC patients (OR=0.097, 0.121, 0.100, p<0.05). The curve fitting results showed that there was a negative correlation between the GCP and LNM in EGC, which was consistent between different tumor sites, size, ulceration, differentiation types, depth of tumor invasion, lymphovascular invasion, and no significant interaction was found among these factors (p for interaction range 0.224-0.717). GCP is closely related to LNM in EGC. Preoperative assessment of whether EGC is combined with GCP is beneficial for the assessment of the risk of LNM.

Effects of group psychological intervention combined with pulmonary rehabilitation exercises on anxiety and sleep disorders in patients with mild coronavirus disease 2019 (COVID-19) infections in a Fangcang hospital.

Fangcang hospitals, as tentative hospitals built to treat a huge turnover of patients with mild coronavirus disease 2019 (COVID-19) infections, have played a pivotal role to slow down the pandemic spread in China in 2020. However, anxiety and sleep disorders remain tough to address during the treatments. In this study, group psychological intervention in combination with pulmonary rehabilitation exercises were conducted in the trial group for the patients with mild COVID-19 infections in a Fangcang Hospital to mitigate the patients' anxiety and sleep disorders, while conventional nursing methods were done in the control group, with 70 randomly picked patients in each group. Effects were assessed through questionnaire method using state anxiety questionnaire (SAI) and Pittsburgh sleep quality index scale (PQSI) rating investigation. Results showed that both SAI and PSQI scores of the trial group were significantly lower than those of the control group (P < 0.05). The SAI scores of the trial group and the control group were 38.5 ± 13.2 and 45.8 ± 10.4 points (t = 3.600, P < 0.001), respectively, and the PSQI scores were 5.6 ± 3.0 and 7.1 ± 3.0 points (t = 2.982, P < 0.01), respectively. Our methods have significant advantages over conventional nursing methods to mitigate anxiety and sleep disorders for the patients with mild COVID-19 infections in the Fangcang Hospital.

Altered Topological Properties of Grey Matter Structural Covariance Networks in Complete Thoracic Spinal Cord Injury Patients: A Graph Theoretical Network Analysis.

Purpose: This study is aimed at investigating brain structural changes and structural network properties in complete spinal cord injury (SCI) patients, as well as their relationship with clinical variables. Materials and Methods: Structural MRI of brain was acquired in 24 complete thoracic SCI patients (38.50 ± 11.19 years, 22 males) within the first postinjury year, while 26 age- and gender-matched healthy participants (38.38 ± 10.63 years, 24 males) were enrolled as control. The voxel-based morphometry (VBM) approach and graph theoretical network analysis based on cross-subject grey matter volume- (GMV-) based structural covariance networks (SCNs) were conducted to investigate the impact of SCI on brain structure. Partial correlation analysis was performed to explore the relationship between the GMV of structurally changed brain regions and SCI patients' clinical variables, including injury duration, injury level, Visual Analog Scale (VAS), American Spinal Injury Association Impairment Scale (AIS), International Classification of Functioning, Disability and Health (ICF) scale, Self-rating Depression Scale (SDS), and Self-rating Anxiety Scale (SAS), after removing the effects of age and gender. Results: Compared with healthy controls, SCI patients showed higher SDS score (t = 4.392 and p < 0.001). In the VBM analysis, significant GMV reduction was found in the left middle frontal cortex, right superior orbital frontal cortex (OFC), and left inferior OFC. No significant difference was found in global network properties between SCI patients and healthy controls. In the regional network properties, significantly higher betweenness centrality (BC) was noted in the right anterior cingulum cortex (ACC) and left inferior OFC and higher nodal degree and efficiency in bilateral middle OFCs, while decreased BC was noted in the right putamen in SCI patients. Only negative correlation was found between GMV of right middle OFC and SDS score in SCI patients (r = -0.503 and p = 0.017), while no significant correlation between other abnormal brain regions and any of the clinical variables (all p > 0.05). Conclusions: SCI patients would experience depressive and/or anxious feelings at the early stage. Their GMV reduction mainly involved psychology-cognition related rather than sensorimotor brain regions. The efficiency of regional information transmission in psychology-cognition regions increased. Greater GMV reduction in psychology region was related with more severe depressive feelings. Therefore, early neuropsychological intervention is suggested to prevent psychological and cognitive dysfunction as well as irreversible brain structure damage.

Spatial patterns of intrinsic brain activity and functional connectivity in facial synkinesis patients.

OBJECTIVES: As one of the most objectionable sequelae of facial paralysis, patients with facial synkinesis are more likely to be depressed and have lower quality of life than other facial paralysis patients. However, there is no research on the spatial patterns of intrinsic brain activity and functional connectivity in these patients. The objective of this study was to investigate the spatial patterns and cerebral plasticity of facial synkinesis patients. METHODS: A total of 20 facial synkinesis patients (18 men and 2 women; mean age: 33.35 ± 6.97 years old) and 19 healthy controls (17 men and 2 women; mean age: 33.21 ± 6.75 years old) were enrolled in this study. resting-state functional magnetic resonance imaging (rs-fMRI) data were collected, and the amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC) were calculated for each participant. Two-sample t-tests were performed to compare the ALFF, ReHo, and DC maps between the two groups. RESULTS: Compared with the healthy controls, facial synkinesis patients exhibited decreased ALFF in the fusiform gyrus, lingual gyrus, parahippocampal gyrus, triangular inferior frontal gyrus, precentral gyrus, postcentral gyrus, cingulate gyrus, superior frontal gyrus, precuneus, caudate nucleus and thalamus; decreased ReHo in the cingulate gyrus, superior frontal gyrus, insula, superior temporal gyrus, orbital middle frontal gyrus, caudate nucleus and thalamus; and decreased DC in the frontal lobe, insula, cingulate gyrus, superior temporal gyrus, lenticular putamen, hippocampus and parahippocampal gyrus. We found significant overlap in the superior frontal gyrus across the ALFF, ReHo and DC analyses. CONCLUSIONS: In facial synkinesis patients, the neurological activity in brain areas is reduced and the local synchronization in motion-related brain regions is decreased. The superior frontal gyrus could be a crucial region in the unique spatial patterns of intrinsic brain activity and functional connectivity in these patients.

Structural remodeling secondary to functional remodeling in advanced-stage peripheral facial neuritis.

BACKGROUND: Structural remodeling is a classic manifestation of disease decompensation. Facial synkinesis is the most troubling sequela of peripheral facial neuritis, and its structural remodeling, especially in white matter (WM), is still poorly understood. Therefore, understanding WM microstructure is important for predicting WM pathology and for early intervention in facial synkinesis patients. METHODS: A total of 20 facial synkinesis patients (18 men and 2 women; mean age, 33.35 ± 6.97 years old) and 19 healthy controls (17 men and 2 women; mean age, 33.21 ± 6.75 years old) were enrolled in this study. rs-fMRI data, diffusion tensor imaging (DTI) data, and Beck's Depression Inventory (BDI) data were collected, and tract-based spatial statistics (TBSS) and voxel-mirrored homotopic connectivity (VMHC) values were used to analyze changes in WM microstructure and interhemispheric coordination. RESULTS: Compared with the healthy controls, facial synkinesis patients exhibited significantly lower regional fractional anisotropy (FA) in the genu of the corpus callosum and the body of the corpus callosum, significantly higher regional FA in the retrolenticular part of the internal capsule, and significantly decreased VMHC values bilaterally in the orbital inferior frontal gyri, the fusiform gyri, the superior temporal gyri, the superior frontal gyri, and the supplementary motor areas. Furthermore, a lower regional FA in the genu of the corpus callosum was correlated with higher BDI scores in facial synkinesis patients. CONCLUSION: Structural remodeling, especially changes in white matter microstructure, may be the central mechanism for severe sequelae of peripheral facial neuritis.

Acupuncture Induces Reduction in Limbic-Cortical Feedback of a Neuralgia Rat Model: A Dynamic Causal Modeling Study.

Background: Neuropathic pain after brachial plexus avulsion remained prevalent and intractable currently. However, the neuroimaging study about neural mechanisms or etiology was limited and blurred. Objective: This study is aimed at investigating the effect of electroacupuncture on effective connectivity and neural response in corticolimbic circuitries during implicit processing of nociceptive stimulus in rats with brachial plexus pain. Methods: An fMRI scan was performed in a total of 16 rats with brachial plexus pain, which was equally distributed into the model group and the electroacupuncture group. The analysis of task-dependent data determined pain-related activation in each group. Based on those results, several regions including AMY, S1, and h were recruited as ROI in dynamic causal modeling (DCM) analysis comparing evidence for different neuronal hypotheses describing the propagation of noxious stimuli in regions of interest and horizontal comparison of effective connections between the model and electroacupuncture groups. Results: In both groups, DCM revealed that noxious stimuli were most likely driven by the somatosensory cortex, with bidirectional propagation with the hypothalamus and amygdala and the interactions in them. Also, the 3-month intervention of acupuncture reduced effective connections of h-S1 and AMY-S1. Conclusions: We showed an evidence that a full connection model within the brain network of brachial plexus pain and electroacupuncture intervention reduces effective connectivity from h and AMY to S1. Our study for the first time explored the relationship of involved brain regions with dynamic causal modeling. It provided novel evidence for the feature of the organization of the cortical-limbic network and the alteration caused by acupuncture.

Motor Control Deficits in Facial Synkinesis Patients: Neuroimaging Evidences of Cerebral Cortex Involvement.

Objective: Facial synkinesis is a severe sequelae of facial nerve malfunction. Once the synkinesis is established, it is extremely difficult for patients to recover. Given that the restoration of motor or sensory function after peripheral nerve injury was closely related with cortical plasticity, we investigated cortical plasticity in facial synkinesis patients by the frequency-specific data which remains largely uncharacterized. Materials and Methods: Resting-state fMRI was conducted in 20 facial synkinesis patients and 19 healthy controls, and the amplitude of low-frequency fluctuation (ALFF) in five different frequency bands (slow-6: 0-0.01 Hz; slow-5: 0.01-0.027 Hz; slow-4: 0.027-0.073 Hz; slow-3: 0.073-0.167 Hz; and slow-2: 0.167-0.25 Hz) was calculated, respectively. And the relationship between ALFF and clinical outcomes was also analyzed. Results: Comparing with the healthy controls, facial synkinesis patients showed significantly different ALFF values, mainly in the sensorimotor areas. Furthermore, increased ALFF of the ipsilateral insula in the slow-6 band was significantly related with better facial nerve function. Conclusion: Increased ALFF values in the ipsilateral insula might reflect an abnormal state of hypercompensation in motor control of facial synkinesis patients. It provided valuable spatial information about the functionally aberrant regions, which implied the possible involvement of motor control system in facial synkinesis.

The Localization Research of Brain Plasticity Changes after Brachial Plexus Pain: Sensory Regions or Cognitive Regions?

Objective: Neuropathic pain after brachial plexus injury remains an increasingly prevalent and intractable disease due to inadequacy of satisfactory treatment strategies. A detailed mapping of cortical regions concerning the brain plasticity was the first step of therapeutic intervention. However, the specific mapping research of brachial plexus pain was limited. We aimed to provide some localization information about the brain plasticity changes after brachial plexus pain in this preliminary study. Methods: 24 Sprague-Dawley rats received complete brachial plexus avulsion with neuropathic pain on the right forelimb successfully. Through functional imaging of both resting-state and block-design studies, we compared the amplitude of low-frequency fluctuations (ALFF) of premodeling and postmodeling groups and the changes of brain activation when applying sensory stimulation. Results: The postmodeling group showed significant decreases on the mechanical withdrawal threshold (MWT) in the bilateral hindpaws and thermal withdrawal latency (TWL) in the left hindpaw than the premodeling group (P < 0.05). The amplitude of low-frequency fluctuations (ALFF) of the postmodeling group manifested increases in regions of the left anterodorsal hippocampus, left mesencephalic region, left dorsal midline thalamus, and so on. Decreased ALFF was observed in the bilateral entorhinal cortex compared to that of the premodeling group. The results of block-design scan showed significant differences in regions including the limbic/paralimbic system and somatosensory cortex. Conclusion: We concluded that the entorhinal-hippocampus pathway, which was part of the Papez circuit, was involved in the functional integrated areas of brachial plexus pain processing. The regions in the "pain matrix" showed expected activation when applying instant nociceptive stimulus but remained silent in the resting status. This research confirmed the involvement of cognitive function, which brought novel information to the potential new therapy for brachial plexus pain.

Synthesis and pharmacological evaluation of novel chromone derivatives as balanced multifunctional agents against Alzheimer's disease.

In a continuing effort to develop multitargeted compounds as potential treatment agents against Alzheimer's disease (AD), a series of chromone derivatives were designed, synthesized and evaluated. In vitro assay indicated that most of the target compounds have both MAOs inhibition activities, antioxidant activity and biometal chelating ability. Especially, compound s19 exhibits good inhibitory potency for inhibition of MAOs (IC50 value of 5.12µM for hMAO-A and 0.816µM for hMAO-B), moderate inhibition of Aß aggregation (75.1% at 20µM), metal chelation, control of ROS generation and antioxidant activity (ORAC=3.62). In addition, s19 could reduce PC12 cells death induced by oxidative stress and penetrate the blood-brain barrier (BBB). Taken together, these results suggested that s19 might be a promising multitargeted compound for AD treatment.