Bioactive components and potential mechanisms of Biqi Capsule in the treatment of osteoarthritis: based on chondroprotective and anti-inflammatory activity.

Cartilage damage and synovial inflammation are vital pathological changes in osteoarthritis (OA). Biqi Capsule, a traditional Chinese medicine formula used for the clinical treatment of arthritis in China, yields advantages in attenuating OA progression. The drawback here is that the bioactive components and pharmacological mechanisms by which Biqi Capsule exerts its anti-inflammatory and chondroprotective effects have yet to be fully clarified. For in vivo studies, a papain-induced OA rat model was established to explore the pharmacological effects and potential mechanisms of Biqi Capsule against OA. Biqi Capsule alleviated articular cartilage degeneration and chondrocyte damage in OA rats and inhibited the phosphorylation of NF-κB and the expression of pro-inflammatory cytokines in synovial tissue. Network pharmacology analysis suggested that the primary biological processes regulated by Biqi Capsule are inflammation and oxidative stress, and the critical pathway regulated is the PI3K/AKT signaling pathway. The result of this analysis was later verified on SW1353 cells. The in vitro studies demonstrated that Glycyrrhizic Acid and Liquiritin in Biqi Capsule attenuated H2O2-stimulated SW1353 chondrocyte damage via activation of PI3K/AKT/mTOR pathway. Moreover, Biqi Capsule alleviated inflammatory responses in LPS-stimulated RAW264.7 macrophages via the NF-κB/IL-6 pathway. These observations were suggested to have been facilitated by Brucine, Liquiritin, Salvianolic Acid B, Glycyrrhizic Acid, Cryptotanshinone, and Tanshinone ⅡA. Put together, this study partially clarifies the pharmacological mechanisms and the bioactive components of Biqi capsules against OA and suggests that it is a promising therapeutic option for the treatment of OA. Chemical compounds studied in this article. Strychnine (Pubchem CID:441071); Brucine (Pubchem CID:442021); Liquiritin (Pubchem CID:503737); Salvianolic Acid B (Pubchem CID:6451084); Glycyrrhizic Acid (Pubchem CID:14982); Cryptotanshinone (Pubchem CID:160254); Tanshinone ⅡA (Pubchem CID:164676).

Aberrant Brain Triple-Network Effective Connectivity Patterns in Type 2 Diabetes Mellitus.

INTRODUCTION: Aberrant brain functional connectivity network is thought to be related to cognitive impairment in patients with type 2 diabetes mellitus (T2DM). This study aims to investigate the triple-network effective connectivity patterns in patients with T2DM within and between the default mode network (DMN), salience network (SN), and executive control network (ECN) and their associations with cognitive declines. METHODS: In total, 92 patients with T2DM and 98 matched healthy controls (HCs) were recruited and underwent resting-state functional magnetic resonance imaging (rs-fMRI). Spectral dynamic causal modeling (spDCM) was used for effective connectivity analysis within the triple network. The posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC), lateral prefrontal cortex (LPFC), supramarginal gyrus (SMG), and anterior insula (AINS) were selected as the regions of interest. Group comparisons were performed for effective connectivity calculated using the fully connected model, and the relationships between effective connectivity alterations and cognitive impairment as well as clinical parameters were detected. RESULTS: Compared to HCs, patients with T2DM exhibited increased or decreased effective connectivity patterns within the triple network. Furthermore, diabetes duration was significantly negatively correlated with increased effective connectivity from the r-LPFC to the mPFC, while body mass index (BMI) was significantly positively correlated with increased effective connectivity from the l-LPFC to the l-AINS (r = - 0.353, p = 0.001; r = 0.377, p = 0.004). CONCLUSION: These results indicate abnormal effective connectivity patterns within the triple network model in patients with T2DM and provide new insight into the neurological mechanisms of T2DM and related cognitive dysfunction.

Disrupted Effective Connectivity within the Fronto-Thalamic Circuit in Pontine Infarction: A Spectral Dynamic Causal Modeling Study.

This study aims to investigate alterations in effective connectivity (EC) within the fronto-thalamic circuit and their associations with motor and cognitive declines in pontine infarction (PI). A total of 33 right PI patients (RPIs), 38 left PI patients (LPIs), and 67 healthy controls (HCs) were recruited. The spectral dynamic causal modeling (spDCM) approach was used for EC analysis within the fronto-thalamic circuit, including the thalamus, caudate, supplementary motor area (SMA), medial prefrontal cortex (mPFC), and anterior cingulate cortex (ACC). The EC differences between different sides of the patients and HCs were assessed, and their correlations with motor and cognitive dysfunctions were analyzed. The LPIs showed increased EC from the mPFC to the R-SMA and decreased EC from the L-thalamus to the ACC, the L-SMA to the R-SMA, the R-caudate to the R-thalamus, and the R-thalamus to the ACC. For RPIs, the EC of the R-caudate to the mPFC, the L-thalamus and L-caudate to the L-SMA, and the L-caudate to the ACC increased obviously, while a lower EC strength was shown from the L-thalamus to the mPFC, the LSMA to the R-caudate, and the R-SMA to the L-thalamus. The EC from the R-caudate to the mPFC was negatively correlated with the MoCA score for RPIs, and the EC from the R-caudate to the R-thalamus was negatively correlated with the FMA score for LPIs. The results demonstrated EC within the fronto-thalamic circuit in PI-related functional impairments and reveal its potential as a novel imaging marker.

Disrupted resting-state functional connectivity and network topology in mild traumatic brain injury: an arterial spin labelling study.

Mild traumatic brain injury can cause different degrees of cognitive impairment and abnormal brain structure and functional connectivity, but there is still a lack of research on the functional connectivity and topological organization of cerebral blood flow fluctuations. This study explored the cerebral blood flow, functional connectivity and topological organization of the cerebral blood flow network in acute mild traumatic brain injury patients. In total, 48 mild traumatic brain injury patients and 46 well-matched healthy controls underwent resting-state arterial spin labelling perfusion MRI and neuropsychological assessments. The functional connectivity and topological organization of the cerebral blood flow network were analysed. Then, the correlation between the changes in cerebral blood flow network characteristics and cognitive function was explored. Acute mild traumatic brain injury patients showed decreased cerebral blood flow in the right insula and increased cerebral blood flow in the right inferior temporal gyrus and left superior temporal gyrus. Abnormal cerebral blood flow network connection patterns mainly occur in sensorimotor network, default mode network, cingulo-opercular network and occipital network-related regions. Furthermore, mild traumatic brain injury disrupted the topological organization of the whole brain, which manifested as (i) reduced global efficiency; (ii) abnormal degree centrality, betweenness centrality, nodal clustering coefficient and nodal efficiency; and (iii) decreased intermodular connectivity between the occipital network and sensorimotor network. Finally, the change in network topology was correlated with the cognitive score of the mild traumatic brain injury. This study provided evidence of abnormal functional connectivity and network topology based on cerebral blood flow in acute mild traumatic brain injury patients, revealing their potential use as early markers for mild traumatic brain injury, which may contribute to both disease diagnosis and assessment.

A deep learning-based model for prediction of hemorrhagic transformation after stroke.

Hemorrhagic transformation (HT) is one of the most serious complications after endovascular thrombectomy (EVT) in acute ischemic stroke (AIS) patients. The purpose of this study is to develop and validate deep-learning (DL) models based on multiparametric magnetic resonance imaging (MRI) to automatically predict HT in AIS patients. Multiparametric MRI and clinical data of AIS patients with EVT from two centers (data set 1 for training and testing: n = 338; data set 2 for validating: n = 54) were used in the DL models. The acute infarction area of diffusion-weighted imaging (DWI) and hypoperfusion of perfusion-weighted imaging (PWI) was labeled manually. Two forms of data sets (volume of interest [VOI] data sets and slice data sets) were analyzed, respectively. The models based on single parameter and multiparameter models were developed and validated to predict HT in AIS patients after EVT. Performance was evaluated by area under the receiver-operating characteristic curve (AUC), accuracy (ACC), sensitivity, specificity, negative predictive value, and positive predictive value. The results showed that the performance of single parameter model based on MTT (VOI data set: AUC = 0.933, ACC = 0.843; slice data set: AUC = 0.945, ACC = 0.833) and TTP (VOI data set: AUC = 0.916, ACC = 0.873; slice data set: AUC = 0.889, ACC = 0.818) were better than the other single parameter model. The multiparameter model based on DWI & MTT & TTP & Clinical (DMTC) had the best performance for predicting HT (VOI data set: AUC = 0.948, ACC = 0.892; slice data set: AUC = 0.932, ACC = 0.873). The DMTC model in the external validation set achieved similar performance with the testing set (VOI data set: AUC = 0.939, ACC = 0.884; slice data set: AUC = 0.927, ACC = 0.871) (p > 0.05). The proposed clinical, DWI, and PWI multiparameter DL model has great potential for assisting the periprocedural management in the early prediction HT of the AIS patients with EVT.

Radiomics Analysis of Diffusion-Weighted Imaging and Long-Term Unfavorable Outcomes Risk for Acute Stroke.

BACKGROUND: Diffusion-weighted imaging radiomics could be used as prognostic biomarkers in acute ischemic stroke. We aimed to identify a clinical and diffusion-weighted imaging radiomics model for individual unfavorable outcomes risk assessment in acute ischemic stroke. METHODS: A total of 1716 patients with acute ischemic stroke from 2 centers were divided into a training cohort and a validation cohort. Patient outcomes were measured with the modified Rankin Scale score. An unfavorable outcome was defined as a modified Rankin Scale score greater than 2. The primary end point was all-cause mortality or outcomes 1 year after stroke. The MRI-DRAGON score was calculated based on previous publications. We extracted and selected the infarct features on diffusion-weighted imaging to construct a radiomic signature. The clinic-radiomics signature was built by measuring the Cox proportional risk regression score (CrrScore) and compared with the MRI-DRAGON score and the ClinicScore. CrrScore model performance was estimated by 1-year unfavorable outcomes prediction. RESULTS: A high radiomic signature predicted a higher probability of unfavorable outcomes than a low radiomic signature in the training (hazard ratio, 3.19 [95% CI, 2.51-4.05]; P<0.0001) and validation (hazard ratio, 3.25 [95% CI, 2.20-4.80]; P<0.0001) cohorts. The diffusion-weighted imaging Alberta Stroke Program Early CT Score, age, glucose level before therapy, National Institutes of Health Stroke Scale score on admission, glycated hemoglobin' radiomic signature, hemorrhagic infarction, and malignant cerebral edema were associated with an unfavorable outcomes risk after multivariable adjustment. A CrrScore nomogram was developed to predict outcomes and had the best performance in the training (area under the curve, 0.862) and validation cohorts (area under the curve, 0.858). The CrrScore model time-dependent areas under the curve of the probability of unfavorable outcomes at 1 year in the training and validation cohorts were 0.811 and 0.801, respectively. CONCLUSIONS: The CrrScore model allows the accurate prediction of patients with acute ischemic stroke outcomes and can potentially guide rehabilitation therapies for patients with different risks of unfavorable outcomes.

Causal interactions with an insular-cortical network in mild traumatic brain injury.

PURPOSE: This study aimed to investigate the insula-based directional effective connectivity in mild traumatic brain injury (mTBI) using resting-state functional magnetic resonance imaging (fMRI) and to explore its relationship with cognitive performance. METHODS: Sixty mTBI patients and 55 age-, gender- and years of education- matched healthy controls (HC) were recruited in this study. Using granger causality analysis (GCA), we selected bilateral insula as two individual seed regions to compare the difference of directional effective connectivity of insula between mTBI group and HC group, and analyze its relationship with cognitive performance. RESULTS: Compared with HC, acute mTBI group showed decreased outflows from the left insula to the left middle frontal gyrus (MFG) and right rolandic operculum (Rol), increased inflow from the left supplementary motor area (SMA) to the left insula, decreased outflows from the right insula to the left superior frontal gyrus (SFG), as well as increased outflows from the right insula to the left superior temporal gyrus (STG). No significantly different inflows to the right insula from other regions were found. Correlation analyses revealed that the abnormal connectivity between insula and MFG, as well as insula and STG were associated with the cognitive function score. CONCLUSIONS: Our data demonstrated abnormalities in the effective connection pathways of insula in acute mTBI patients, while abnormal effective connectivity significantly correlated with cognitive function score. These findings may shed light on the pathophysiological mechanisms of cognitive impairment after mTBI.

Decreased brain functional connectivity associated with cognitive dysfunction in women with second pregnancy.

Purpose: Previous research has found that women with second pregnancy may have an increased risk of cognitive dysfunction. This study aims to investigate the intrinsic functional connectivity (FC) pattern of the DMN anchored on posterior cingulate cortex (PCC) in postpartum women, especially the parous women using resting-state functional magnetic resonance imaging (rs-fMRI). Methods: Twenty parous women, 26 primiparous women, and 30 nulliparous women were included for rs-fMRI scan. They were age and education well matched. A seed based FC method was conducted to reveal FC patterns with other brain regions using a region of interest in the PCC. The relationships between FC patterns and cognitive performance were further detected. Results: Relative to primiparous women, parous women had significantly decreased FC primarily between the PCC and the right middle frontal gyrus and right parahippocampal gyrus. The decreased FC to the right parahippocampal gyrus in parous women was positively associated with the reduced DST scores (rho = 0.524, p = 0.031). Moreover, parous women compared with nulliparous women showed significantly decreased FC between the PCC and the left superior frontal gyrus and left middle frontal gyrus. The reduced FC to the left superior frontal gyrus in parous women was also positively associated with the lower DST scores (rho = 0.550, p = 0.022). Conclusion: Our result highlights that women with second pregnancy revealed decreased FC between the DMN regions with the parahippocampal gyrus and prefrontal cortex, which was correlated with specific impaired cognitive function. This study may provide new insights into the neuropathological mechanisms of postpartum cognitive impairment and enhance our understanding of the neurobiological aspects during postpartum period.

Rich-club reorganization of functional brain networks in acute mild traumatic brain injury with cognitive impairment.

Background: Mild traumatic brain injury (mTBI) is typically characterized by temporally limited cognitive impairment and regarded as a brain connectome disorder. Recent findings have suggested that a higher level of organization named the "rich-club" may play a central role in enabling the integration of information and efficient communication across different systems of the brain. However, the alterations in rich-club organization and hub topology in mTBI and its relationship with cognitive impairment after mTBI have been scarcely elucidated. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected from 88 patients with mTBI and 85 matched healthy controls (HCs). Large-scale functional brain networks were established for each participant. Rich-club organizations and network properties were assessed and analyzed between groups. Finally, we analyzed the correlations between the cognitive performance and changes in rich-club organization and network properties. Results: Both mTBI and HCs groups showed significant rich-club organization. Meanwhile, the rich-club organization was aberrant, with enhanced functional connectivity (FC) among rich-club nodes and peripheral regions in acute mTBI. In addition, significant differences in partial global and local network topological property measures were found between mTBI patients and HCs (P<0.01). In patients with mTBI, changes in rich-club organization and network properties were found to be related to early cognitive impairment after mTBI (P<0.05). Conclusions: Our findings suggest that such patterns of disruption and reorganization will provide the basic functional architecture for cognitive function, which may subsequently be used as an earlier biomarker for cognitive impairment after mTBI.

Machine Learning Based on Diffusion Kurtosis Imaging Histogram Parameters for Glioma Grading.

Glioma grading plays an important role in surgical resection. We investigated the ability of different feature reduction methods in support vector machine (SVM)-based diffusion kurtosis imaging (DKI) histogram parameters to distinguish glioma grades. A total of 161 glioma patients who underwent magnetic resonance imaging (MRI) from January 2017 to January 2020 were included retrospectively. The patients were divided into low-grade (n = 61) and high-grade (n = 100) groups. Parametric DKI maps were derived, and 45 features from the DKI maps were extracted semi-automatically for analysis. Three feature selection methods [principal component analysis (PCA), recursive feature elimination (RFE) and least absolute shrinkage and selection operator (LASSO)] were used to establish the glioma grading model with an SVM classifier. To evaluate the performance of SVM models, the receiver operating characteristic (ROC) curves of SVM models for distinguishing glioma grades were compared with those of conventional statistical methods. The conventional ROC analysis showed that mean diffusivity (MD) variance, MD skewness and mean kurtosis (MK) C50 could effectively distinguish glioma grades, particularly MD variance. The highest classification distinguishing AUC was found using LASSO at 0.904 ± 0.069. In comparison, classification AUC by PCA was 0.866 ± 0.061, and 0.899 ± 0.079 by RFE. The SVM-PCA model with the lowest AUC among the SVM models was significantly better than the conventional ROC analysis (z = 1.947, p = 0.013). These findings demonstrate the superiority of DKI histogram parameters by LASSO analysis and SVM for distinguishing glioma grades.

Aberrant static and dynamic functional network connectivity in heart failure with preserved ejection fraction.

AIMS: Heart failure may lead to brain functional alterations related to cognitive impairment. This study aimed to detect alterations of static functional network connectivity (FNC) and dynamic FNC in heart failure with preserved ejection fraction (HFpEF) and to estimate the association between the altered FNC and clinical features related to HFpEF. METHODS AND RESULTS: The clinical and resting-state functional magnetic resonance imaging (fMRI) data of HFpEF patients (n = 35) and healthy controls (HCs) (n = 35) were acquired at baseline. Resting-state networks (RSNs) were established based on independent component analysis (ICA) and FNC analyses were performed. The associations between the FNC abnormalities and clinical features related to HFpEF were analysed. Compared with HCs, HFpEF patients showed decreased functional connectivity within the default mode network, left frontoparietal network, and right frontoparietal network and increased functional connectivity within the right frontoparietal network and visual network. Negative correlations were observed between decreased dynamic FNC and the left ventricular end-diastolic diameter (LVDd) (r = -0.435, P = 0.015) as well as the left ventricular end-systolic diameter (LVDs) (r = -0.443, P = 0.013). CONCLUSIONS: The FNC disruption and altered temporal properties of functional dynamics in HFpEF patients may reflect the neural mechanisms of brain injury after HFpEF, which may deepen our understanding of the disease.

N6-methyladenosine RNA demethylase ALKBH5 is testis-specifically downregulated in hybrid male sterile dzo and is a target gene of bta-miR-200a.

N6-methyladenosine (m6A) is the most common RNA methylation modification in mammals, which is controlled in the male germline to ensure coordinated gene expression in the entire process of spermatogenesis. Dzo is the male offspring of a cross between the domestic cattle (Bos taurus) and yak (Bos grunniens), and is sterile. This study aimed to investigate whether m6A-associated genes are linked with dzo male sterility. The mRNA expression pattern of m6A-associated genes and spermatogenesis-related genes modified by m6A was characterized in cattle, yak, and dzo. Compared with fertile cattle and yak, m6A erasing (ALKBH5 and FTO), writing (METTL14, WTAP, and ZC3H13), and reading (YTHDC2, YTHDF1, and YTHDF2) were testis-specifically downregulated in infertile dzo. The expression of m6A target genes in spermatogonial self-renewal and proliferation (BCL6B, FOXO1, TAF4B, and FGFR1) and differentiation genes (DNMT3B and SOHLH2) were dereguleted in dzo testis. Immunofluorescent staining showed that intense ALKBH5 immunoreactivity was present in spermatogonia, primary spermatocytes, and round spermatids of cattle and yak testis. However, the number of ALKBH5 immunoreactive-positive cells were significantly reduced in dzo testis, especially in primary spermatocytes and round spermatids. Whole genome bisulfite-seq data showed that the promoter regions of FTO and YTHDC2 genes were hypermethylated in dzo testis. Moreover, bta-miR-200a was significantly downregulated in dzo testis, and it targeted the m6A-associated genes such as ALKBH5, FTO, WTAP, and YTHDF2. In conclusion, mRNA of ALKBH5 was testis-specifically downregulated in dzo, which may be because fewer specific spermatogenic cells express this gene. The role of m6A-associated genes in dzo male sterility and the interaction of DNA methylation and miRNA with m6A-associated protein expression need to be further explored.

Aberrant Static and Dynamic Functional Network Connectivity in Acute Mild Traumatic Brain Injury with Cognitive Impairment.

PURPOSE: This study aimed to investigate differences in static and dynamic functional network connectivity (FNC) and explore their association with neurocognitive performance in acute mild traumatic brain injury (mTBI). METHODS: A total of 76 patients with acute mTBI and 70 age-matched and sex-matched healthy controls were enrolled (age 43.79 ± 10.22 years vs. 45.63 ± 9.49 years; male/female: 34/42 vs. 38/32; all p > 0.05) and underwent resting-state functional magnetic resonance imaging (fMRI) scan (repetition time/echo time = 2000/30 ms, 230 volumes). Independent component analysis was conducted to evaluate static and dynamic FNC patterns on the basis of nine resting-state networks, namely, auditory network (AUDN), dorsal attention network (dAN), ventral attention network (vAN), default mode network (DMN), left frontoparietal network (LFPN), right frontoparietal network (RFPN), somatomotor network (SMN), visual network (VN), and salience network (SN). Spearman's correlation among aberrances in FNC values, and Montreal cognitive assessment (MoCA) scores was further measured in mTBI. RESULTS: Compared with controls, patients with mTBI showed wide aberrances of static FNC, such as reduced FNC in DMN-vAN and VN-vAN pairs. The mTBI patients exhibited aberrant dynamic FNC in state 2, involving reduced FNC aberrance in the vAN with AUDN, VN with DMN and dAN, and SN with SMN and vAN. Reduced dFNC in the SN-vAN pair was negatively correlated with the MoCA score. CONCLUSION: Our findings suggest that aberrant static and dynamic FNC at the acute stage may contribute to cognitive symptoms, which not only may expand knowledge regarding FNC cognition relations from the static perspective but also from the dynamic perspective.

Reduced functional network connectivity is associated with upper limb dysfunction in acute ischemic brainstem stroke.

This study aimed to detect alterations in intra- and inter-network functional connectivity (FC) of multiple networks in acute brainstem ischemic stroke patients, and the relationship between FC and movement assessment scores to assess their ability to predict upper extremity motor impairment. Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from acute brainstem ischemic stroke patients (n = 50) and healthy controls (HCs) (n = 45). Resting-state networks (RSNs) were established based on independent component analysis (ICA) and the functional network connectivity (FNC) analysis was performed. Subsequently, correlation analysis was subsequently used to explore the relationship between FNC abnormalities and upper extremity motor impairment. Altered FC within default mode network (DMN), executive control network (ECN), the salience network (SN), auditory network (AN), and cerebellum network (CN) were found in the acute brainstem ischemic stroke group relative to HCs. Moreover, different patterns of altered network interactions were found between the patients and HCs, including the SN-CN, SN-AN, and ECN-DMN connections. Correlations between functional disconnection and upper limb dysfunction measurements in acute brainstem ischemic stroke patients were also found. This study intimated that widespread FNC impairment and altered integration existed in brainstem ischemic stroke at acute stage, suggesting that FNC disruption may be applied for early diagnosis and prediction of upper limb dysfunction in acute brainstem ischemic stroke.

Altered static and dynamic functional network connectivity in post-traumatic headache.

BACKGROUND: Post-traumatic headache (PTH) is a very common symptom following mild traumatic brain injury (mTBI), yet much remains unknown about the underlying pathophysiological mechanisms of PTH. Neuroimaging studies suggest that aberrant functional network connectivity (FNC) may be an important factor in pain disorders. The present study aimed to investigate the functional characteristics of static FNC (sFNC) and dynamic FNC (dFNC) in mTBI patients with PTH. METHODS: With Institutional Review Board (IRB) approval, we prospectively recruited 50 mTBI patients with PTH, who were diagnosed with ICHD-3 beta diagnostic criteria and 39 mTBI without PTH who were well matched for age, gender and education. Resting-state functional magnetic resonance imaging (fMRI) scanning (3.0 T, Philips Medical Systems, Netherlands), Montreal Cognitive Assessment (MoCA) and headache symptom measurement (headache frequency and headache intensity) were performed. The resting-state fMRI sequence took 8 min and 10 s. Independent component analysis and sliding window method were applied to examine the FNC on the basis of nine resting-state networks, namely, default mode network (DMN), sensorimotor network (SMN), executive control network (ECN), auditory network (AuN), attention network (AN), salience network (SN), visual network (VN), and cerebellum network (CN). The differences in sFNC and dFNC were determined and correlated with clinical variables using Pearson rank correlation. RESULTS: For sFNC, compared with mTBI patients without PTH, mTB with PTH group showed four altered interactions, including decreased interactions in SN-SMN and VN-DMN pairs, increased sFNC in SN-ECN and SMN-DMN pairs. For dFNC, significant group differences were found in State 2, including increased connectivity alteration in the DMN with CN, DMN with SMN, and AuN with CN. Significant reduced connectivity changes in the DMN with VN was found in State 4. Furthermore, the number of transitions (r=0.394, p=0.005) between states was positively associated with headache frequency. Additionally, dwell time (r=-0.320, p=0.025) in State 1 was negatively correlated with MoCA score. CONCLUSIONS: MTBI patients with PTH are characterized with altered sFNC and dFNC, which could provide new perspective to understand the neuropathological mechanism underlying the PTH to determine more appropriate management, and may be a useful imaging biomarker for identifying and predicting mTBI with PTH.

Cerebral Blood Flow Difference Between Acute and Chronic Tinnitus Perception: A Perfusion Functional Magnetic Resonance Imaging Study.

Purpose: The central nervous mechanism of acute tinnitus is different from that of chronic tinnitus, which may be related to the difference of cerebral blood flow (CBF) perfusion in certain regions. To verify this conjecture, we used arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) in this study to compare the CBF alterations of patients with acute and chronic tinnitus. Methods: The current study included patients with chronic tinnitus (n = 35), acute tinnitus (n = 30), and healthy controls (n = 40) who were age-, sex-, and education-matched. All participants underwent MRI scanning and then ASL images were obtained to measure CBF of the entire brain and analyze the differences between groups as well as the correlations with tinnitus characteristics. Results: The chronic tinnitus group showed increased z-CBF in the right superior temporal gyrus (STG) and superior frontal gyrus (SFG) when compared with the acute tinnitus patients. Further connectivity analysis found enhanced CBF connectivity between the right STG and fusiform gyrus (FG), the right SFG and left middle occipital gyrus (MOG), as well as the right parahippocampal gyrus (PHG). Moreover, in the chronic tinnitus group, the tinnitus handicap questionnaire (THQ) score was positively correlated with the normalized z-CBF of right STG (r = 0.440, p = 0.013). Conclusion: Our results confirmed that the CBF changes in some brain regions were different between acute and chronic tinnitus patients, which was correlated with certain tinnitus characteristics. This is of great value to further research on chronicity of tinnitus, and ASL has a promising application in the measurement of CBF.

Predictive value of perfusion weighted imaging for early new lesions after stroke patients receive endovascular treatment.

BACKGROUND: Previous studies have focused on early new lesion-associated factors, but the differences in the perfusion status between the at-risk hypoperfusion areas with new lesions and the other hypoperfusion areas in stroke patients before thrombectomy is not clear. We investigated the value of perfusion-weighted imaging (PWI) in predicting early new lesions in patients after stroke. METHODS: Fifty-five acute stroke patients who underwent diffusion-weighted imaging (DWI) and PWI before and after thrombectomy within 24 h were eligible. The PWI parameters of the core infarct areas (high signal tissue on the DWI), the at-risk hypoperfusion areas (hypoperfusion area with new lesions at follow-up PWI) and the other hypoperfusion areas of patients with new lesions were collected. Statistical analysis was performed to predict new lesions after stroke. The differences in the PWI parameters of the core infarct areas, the at-risk hypoperfusion areas and the other hypoperfusion areas were compared. Receiver operating characteristic (ROC) curve analysis was used to assess the predictive value of the PWI parameters (P<0.05) for the occurrence of new lesions in patients with acute stroke after thrombectomy. RESULTS: Fifty-five stroke patients were analyzed, including forty patients (72.73%) with new lesions and fifteen patients (27.27%) without new lesions. Acute stroke patients with new lesions had a longer mean transit time (MTT) and time to peak (TTP) in the at-risk hypoperfusion areas (11.95±3.29; 38.30±11.39) than in the other hypoperfusion areas (8.68±2.08; 29.76±6.86), both of which were significantly different (P<0.0001; P<0.0001, respectively). The ROC analysis showed that the sensitivity and specificity of MTT for predicting the occurrence of new lesions after stroke were 70.00% and 87.50%, respectively; the sensitivity and specificity of TTP were 70.00% and 80.00%, respectively. CONCLUSIONS: MTT and TTP may be useful in predicting early new lesions in acute stroke patients after thrombectomy.

The apheresis platelet donation was increased after a nationwide ban on family/replacement donation in China.

BACKGROUND: A nationwide ban on family/replacement donation (FRD) went into effect on April 1, 2018 in China. To date, no reports relevant to the trend of plateletpheresis donations before and after a nationwide ban on FRD were found. METHODS: We used two independent full samples, consisting of 135,851 and 82,129 plateletpheresis donors from Guangzhou and Chengdu between October 2012 and September 2019, respectively. A pseudo-panel data approach was applied by grouping three time-invariant covariates - gender, blood donation history, and birth year across 14 cross-sections (a 6-month interval each) to form a total of 24 cohort groups (14 × 24 = 336 cohorts, i.e., cells) with each having common covariates. The outcome was average apheresis platelet units per donor in each cell. We performed a two-piecewise linear mixed model with the cross-section (i.e., time) just right before the ban as a time breakpoint (i.e., 11th cross-section) to examine the trend of outcome with the adjustment of three time-invariant covariates. We removed the FRDs in each of the first 11 cross-sections to detect its possible influence on the trend. RESULTS: The final model for the samples from Guangzhou presented a two-piecewise linear trend of the outcome over time with a horizontal line to the left of the breakpoint (ßtimeBefore11 = 0.0111, p = 0.0976) and a significantly positive linear trend to the right (ßtimeAfter11 = 0.0404, p < 0.0001). The male donors and the donors with plateletpheresis donation history had an increased baseline outcome and a significant outcome change over time after the ban. Such a two-piecewise linear trend pattern can be replicated using the samples from Chengdu with some minor variations. Removing the FRD before the ban can change the pattern. CONCLUSION: The significant increase of the average apheresis platelet units per donor over time after the FRD ban may be related to the implement of the FRD ban and the improved donation behavior of male donors and/or donors with platelet donation history after the ban. Our findings may potentially motivate the policymakers in other countries where the FRD for plateletpheresis donation is still legitimate to phase out their FRD strategy and ultimately achieve 100% voluntary plateletpheresis donation.

Alterations of brain network topology and structural connectivity-functional connectivity coupling in capsular versus pontine stroke.

BACKGROUND AND PURPOSE: This study was conducted to investigate whether capsular stroke (CS) and pontine stroke (PS) have different topological alterations of structural connectivity (SC) and functional connectivity (FC), as well as correlations of SC-FC coupling with movement assessment scores. METHODS: Resting-state functional magnetic resonance imaging and diffusion tensor imaging were prospectively acquired in 46 patients with CS, 36 with PS, and 29 healthy controls (HCs). Graph theoretical network analyses of SC and FC were performed. Patients with left and right lesions were analyzed separately. RESULTS: With regard to FC, the PS and CS groups both showed higher local efficiency than the HCs, and the CS group also had a higher clustering coefficient (Cp) than the HCs in the right lesion analysis. With regard to SC, the PS and CS groups both showed different normalized clustering coefficient (γ), small-worldness (σ), and characteristic path length (Lp) compared with the HC group. Additionally, the CS group showed higher normalized characteristic path length (λ) and a lower Cp than the HCs and the PS group showed higher λ and lower global efficiency than the HCs in the right-lesion analysis. However, γ, σ, Cp and Lp were only significantly different in the PS and CS groups compared with the HC group in the right-lesion analysis. Importantly, the CS group was found to have a weaker SC-FC coupling than the PS group and the HC group in the right-lesion analysis. In addition, both patient groups had weaker structural-functional connectome correlation than the HCs. CONCLUSIONS: The CS and PS groups both showed FC and SC disruption and the CS group had a weaker SC-FC coupling than the PS group in the right lesion analysis. This may provide useful information for individualized rehabilitative strategies.

A preliminary study of cortical morphology changes in acute brainstem ischemic stroke patients.

ABSTRACT: The study aimed to explore the cortical thickness and gyrification abnormalities in acute brainstem ischemic patients in both the ipsilateral and contralateral hemisphere compared with healthy controls. Structural magnetic resonance imaging data were prospectively acquired in 48 acute brainstem ischemic patients, 21 patients with left lesion and 27 with right lesion, respectively. Thirty healthy controls were recruited. Cortical morphometry based on surface-based data analysis driven by CAT12 toolbox implemented in SPM12 was used to compare changes in cortical thickness and gyrification. Significant decreases of cortical thickness loss were found in bilateral cerebral hemispheres of the brainstem ischemic patients compared to the healthy controls (P < .05, family-wise error (FWE)-corrected). We also found significant gyrification decreases in the insula, transverse temporal, supramarginal of the ipsilateral on hemisphere in the right brainstem ischemic patients compared to the healthy controls (P < .05, FWE-corrected). Brainstem ischemic patients have widely morphological changes in the early phase and may be helpful in designing individualized rehabilitative strategies for these patients.