Acute limbic system connectivity predicts chronic cognitive function in mild traumatic brain injury: An individualized differential structural covariance network study.

Mild traumatic brain injury (mTBI) is a known risk factor for neurodegenerative diseases, yet the precise pathophysiological mechanisms remain poorly understand, often obscured by group-level analysis in non-invasive neuroimaging studies. Individual-based method is critical to exploring heterogeneity in mTBI. We recruited 80 mTBI patients and 40 matched healthy controls, obtaining high-resolution structural MRI for constructing Individual Differential Structural Covariance Networks (IDSCN). Comparisons were conducted at both the individual and group levels. Connectome-based Predictive Modeling (CPM) was applied to predict cognitive performance based on whole-brain connectivity. During the acute stage of mTBI, patients exhibited significant heterogeneity in the count and direction of altered edges, obscured by group-level analysis. In the chronic stage, the number of altered edges decreased and became more consistent, aligning with clinical observations of acute cognitive impairment and gradual improvement. Subgroup analysis based on loss of consciousness/post-traumatic amnesia revealed distinct patterns of alterations. The temporal lobe, particularly regions related to the limbic system, significantly predicted cognitive function from acute to chronic stage. The use of IDSCN and CPM has provided valuable individual-level insights, reconciling discrepancies from previous studies. Additionally, the limbic system may be an appropriate target for future intervention efforts.

Nuclear translocation of metabolic enzyme PKM2 participates in high glucose-promoted HCC metastasis by strengthening immunosuppressive environment.

Although some cohort studies have indicated a close association between diabetes and HCC, the underlying mechanism about the contribution of diabetes to HCC progression remains largely unknown. In the study, we applied a novel HCC model in SD rat with diabetes and a series of high glucose-stimulated cell experiments to explore the effect of a high glucose environment on HCC metastasis and its relevant mechanism. Our results uncovered a novel regulatory mechanism by which nuclear translocation of metabolic enzyme PKM2 mediated high glucose-promoted HCC metastasis. Specifically, high glucose-increased PKM2 nuclear translocation downregulates chemerin expression through the redox protein TRX1, and then strengthens immunosuppressive environment to promote HCC metastasis. To the best of our knowledge, this is the first report to elucidate the great contribution of a high glucose environment to HCC metastasis from a new perspective of enhancing the immunosuppressive microenvironment. Simultaneously, this work also highlights a previously unidentified non-metabolic role of PKM2 and opens a novel avenue for cross research and intervention for individuals with HCC and comorbid diabetes.

Empagliflozin attenuates liver fibrosis in high-fat diet/streptozotocin-induced mice by modulating gut microbiota.

The effects of SGLT2 inhibitors on hepatic fibrosis in diabetes remain unclear. This study aimed to investigate the effects of empagliflozin on liver fibrosis in high-fat diet/streptozotocin-induced mice and the correlation with gut microbiota. After the application of empagliflozin for 6 weeks, we performed oral glucose tolerance and intraperitoneal insulin tolerance tests to assess glucose tolerance and insulin resistance, and stained liver sections to evaluate histochemical and hepatic pathological markers of liver fibrosis. Moreover, 16S rRNA amplicon sequencing was performed on stool samples to explore changes in the composition of intestinal bacteria. We finally analysed the correlation between gut microbiome and liver fibrosis scores or indicators of glucose metabolism. The results showed that empagliflozin intervention improved glucose metabolism and liver function with reduced liver fibrosis, which might be related to changes in intestinal microbiota. In addition, the abundance of intestinal probiotic Lactobacillus increased, while Ruminococcus and Adlercreutzia decreased after empagliflozin treatment, and correlation analysis showed that the changes in microbiota were positively correlated with liver fibrosis and glucose metabolism. Overall, considering the contribution of the gut microbiota in metabolism, empagliflozin might have improved the beneficial balance of intestinal bacteria composition. The present study provides evidence and indicates the involvement of the gut-liver axis by SGLT2 inhibitors in T2DM with liver fibrosis.

Altered orientation dispersion index of white matter in individuals with insomnia during the COVID-19 pandemic: A study combining neuroimaging technique and Mendelian randomization.

STUDY OBJECTIVES: Coronavirus disease 2019 (COVID-19) can lead to insomnia. However, associations between COVID-19-caused insomnia and white matter (WM) changes are unclear. METHODS: All subjects had ever been infected with COVID-19. We investigated 89 insomniacs (29 chronic insomniacs, 33 new-onset insomniacs, 27 aggravated insomniacs) and 44 matched non-insomnia participants. Neurite orientation dispersion and density imaging (NODDI) was performed to identify micro-structural alterations of WM, and twelve scales related to sleeping status, memory, attention, learning, emotional status, and executive functions were used. Then, correlations between insomnia/cognitive-behavioral functions and diffusion metrics were tested. To eliminate influence of pre-COVID-19 factors on insomnia, causal relationships between COVID-19 and WM changes were validated by Mendelian randomization (MR) analysis. The significant brain regions of COVID-19-caused insomnia were intersected results of tract-based spatial statistics (TBSS) and MR analyses. RESULTS: Compared to non-insomnia group, insomnia group and its subgroups including post-COVID-19 aggravated or unchanged chronic insomnia group had higher orientation dispersion index (ODI) in extensive brain regions. The left superior longitudinal fasciculus (SLF), left posterior thalamic radiation (PTR), and left cingulate gyrus (CG) were specific brain regions in COVID-19-induced insomnia aggravation. After Bonferroni correction, partial correlation analyses within insomnia group showed that ODI in left SLF was positively correlated with Pittsburgh sleep quality index (PSQI), insomnia severity index (ISI), and self-rating anxiety scale (SAS) scores; ODI in the left PTR was positively correlated with PSQI and ISI scores. CONCLUSIONS: This study is a continuation of our previous research, which provided potential biomarkers for COVID-19-induced insomnia.

Gray Matter Thickness and Subcortical Nuclear Volume in Men After SARS-CoV-2 Omicron Infection.

Importance: The clinical manifestations and effects on the brain of the SARS-CoV-2 Omicron variant in the acute postinfection phase remain unclear. Objective: To investigate the pathophysiological mechanisms underlying clinical symptoms and changes to gray matter and subcortical nuclei among male patients after Omicron infection and to provide an imaging basis for early detection and intervention. Design, Setting, and Participants: In this cohort study, a total of 207 men underwent health screening magnetic resonance imaging scans between August 28 and September 18, 2022; among them, 98 provided complete imaging and neuropsychiatric data. Sixty-one participants with Omicron infection were reevaluated after infection (January 6 to 14, 2023). Neuropsychiatric data, clinical symptoms, and magnetic resonance imaging data were collected in the acute post-Omicron period, and their clinical symptoms were followed up after 3 months. Gray matter indexes and subcortical nuclear volumes were analyzed. Associations between changes in gray matter and neuropsychiatric data were evaluated with correlation analyses. Exposures: Gray matter thickness and subcortical nuclear volume change data were compared before and after Omicron infection. Main Outcomes and Measures: The gray matter indexes and subcutaneous nuclear volume were generated from the 3-dimensional magnetization-prepared rapid acquisition gradient echo and were calculated with imaging software. Results: Ninety-eight men underwent complete baseline data collection; of these, 61 (mean [SD] age, 43.1 [9.9] years) voluntarily enrolled in post-Omicron follow-up and 17 (mean [SD] age, 43.5 [10.0] years) voluntarily enrolled in 3-month follow-up. Compared with pre-Omicron measures, Beck Anxiety Inventory scores were significantly increased (median, 4.50 [IQR, 1.00-7.00] to 4.00 [IQR, 2.00-9.75]; P = .006) and depressive distress scores were significantly decreased (median, 18.00 [IQR, 16.00-20.22] to 16.00 [IQR, 15.00-19.00]; P = .003) at the acute post-Omicron follow-up. Fever, headache, fatigue, myalgia, cough, and dyspnea were the main symptoms during the post-Omicron follow-up; among the participants in the 3-month follow-up, fever (11 [64.7%] vs 2 [11.8%]; P = .01), myalgia (10 [58.8%] vs 3 (17.6%]; P = .04), and cough (12 [70.6%] vs 4 [23.5%]; P = .02) were significantly improved. The gray matter thickness in the left precuneus (mean [SD], 2.7 [0.3] to 2.6 [0.2] mm; P < .001) and right lateral occipital region (mean [SD], 2.8 [0.2] to 2.7 [0.2] and 2.5 [0.2] to 2.5 [0.2] mm; P < .001 for both) and the ratio of the right hippocampus volume to the total intracranial volume (mean [SD]. 0.003 [0.0003] to 0.003 [0.0002]; P = .04) were significantly reduced in the post-Omicron follow-up. The febrile group had reduced sulcus depth of the right inferior parietal region compared with the nonfebrile group (mean [SD], 3.9 [2.3] to 4.8 [1.1]; P = .048. In the post-Omicron period, the thickness of the left precuneus was negatively correlated with the Beck Anxiety Inventory scores (r = -0.39; P = .002; false discovery rate P = .02), and the ratio of the right hippocampus to the total intracranial volume was positively correlated with the Word Fluency Test scores (r = 0.34; P = .007). Conclusions and Relevance: In this cohort study of male patients infected with the Omicron variant, the duration of symptoms in multiple systems after infection was short. Changes in gray matter thickness and subcortical nuclear volume injury were observed in the post-Omicron period. These findings provide new insights into the emotional and cognitive mechanisms of an Omicron infection, demonstrate its association with alterations to the nervous system, and verify an imaging basis for early detection and intervention of neurological sequelae.

Differential and correlational tractography as tract-based biomarkers in mild traumatic brain injury: A longitudinal MRI study.

We evaluated the fiber bundles in mild traumatic brain injury (mTBI) patients using differential and correlational tractography in a longitudinal analysis. Diffusion MRI data were acquired in 34 mTBI patients at 7 days (acute stage) and 3 months or longer (chronic stage) after mTBI. Trail Making Test A (TMT-A) and Digital Symbol Substitution Test changes were used to evaluate the cognitive performance. Longitudinal correlational tractography showed decreased anisotropy in the corpus callosum during the chronic mTBI stage. The changes in anisotropy in the corpus callosum were significantly correlated with the changes in TMT-A (false discovery rate [FDR] = 0.000094). Individual longitudinal differential tractography found that anisotropy decreased in the corpus callosum in 30 mTBI patients. Group cross-sectional differential tractography found that anisotropy increased (FDR = 0.02) in white matter in the acute mTBI patients, while no changes occurred in the chronic mTBI patients. Our study confirms the feasibility of using correlational and differential tractography as tract-based monitoring biomarkers to evaluate the disease progress of mTBI, and indicates that normalized quantitative anisotropy could be used as a biomarker to monitor the injury and/or repairs of white matter in individual mTBI patients.

Correlation between cerebral cortex changes and clinical features in patients with neuromyelitis optica spectrum disorder with normal-appearing brain tissue: a case-control study.

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system. However, whether and how cortical changes occur in NMOSD with normal-appearing brain tissue, or whether any cortical changes correlate with clinical characteristics, is not completely clear. The current study recruited 43 patients with NMOSD who had normal-appearing brain tissue and 45 healthy controls matched for age, sex, and educational background from December 2020 to February 2022. A surface-based morphological analysis of high-resolution T1-weighted structural magnetic resonance images was used to calculate the cortical thickness, sulcal depth, and gyrification index. Analysis showed that cortical thickness in the bilateral rostral middle frontal gyrus and left superior frontal gyrus was lower in the patients with NMOSD than in the control participants. Subgroup analysis of the patients with NMOSD indicated that compared with those who did not have any optic neuritis episodes, those who did have such episodes exhibited noticeably thinner cortex in the bilateral cuneus, superior parietal cortex, and pericalcarine cortex. Correlation analysis indicated that cortical thickness in the bilateral rostral middle frontal gyrus was positively correlated with scores on the Digit Symbol Substitution Test and negatively correlated with scores on the Trail Making Test and the Expanded Disability Status Scale. These results are evidence that cortical thinning of the bilateral regional frontal cortex occurs in patients with NMOSD who have normal-appearing brain tissue, and that the degree of thinning is correlated with clinical disability and cognitive function. These findings will help improve our understanding of the imaging characteristics in NMOSD and their potential clinical significance.

Improve follicular thyroid carcinoma diagnosis using computer aided diagnosis system on ultrasound images.

Objective: We aim to leverage deep learning to develop a computer aided diagnosis (CAD) system toward helping radiologists in the diagnosis of follicular thyroid carcinoma (FTC) on thyroid ultrasonography. Methods: A dataset of 1159 images, consisting of 351 images from 138 FTC patients and 808 images from 274 benign follicular-pattern nodule patients, was divided into a balanced and unbalanced dataset, and used to train and test the CAD system based on a transfer learning of a residual network. Six radiologists participated in the experiments to verify whether and how much the proposed CAD system helps to improve their performance. Results: On the balanced dataset, the CAD system achieved 0.892 of area under the ROC (AUC). The accuracy, recall, precision, and F1-score of the CAD method were 84.66%, 84.66%, 84.77%, 84.65%, while those of the junior and senior radiologists were 56.82%, 56.82%, 56.95%, 56.62% and 64.20%, 64.20%, 64.35%, 64.11% respectively. With the help of CAD, the metrics of the junior and senior radiologists improved to 62.81%, 62.81%, 62.85%, 62.79% and 73.86%, 73.86%, 74.00%, 73.83%. The results almost repeated on the unbalanced dataset. The results show the proposed CAD approach can not only achieve better performance than radiologists, but also significantly improve the radiologists' diagnosis of FTC. Conclusions: The performances of the CAD system indicate it is a reliable reference for preoperative diagnosis of FTC, and might assist the development of a fast, accessible screening method for FTC.

Neural activity changes in first-episode, drug-naïve patients with major depressive disorder after transcutaneous auricular vagus nerve stimulation treatment: A resting-state fMRI study.

Introduction: Major depressive disorder (MDD) is a disease with prominent individual, medical, and economic impacts. Drug therapy and other treatment methods (such as Electroconvulsive therapy) may induce treatment-resistance and have associated side effects including loss of memory, decrease of reaction time, and residual symptoms. Transcutaneous auricular vagus nerve stimulation (taVNS) is a novel and non-invasive treatment approach which stimulates brain structures with no side-effects. However, it remains little understood whether and how the neural activation is modulated by taVNS in MDD patients. Herein, we used the regional homogeneity (ReHo) to investigate the brain activity in first-episode, drug-naïve MDD patients after taVNS treatment. Materials and methods: Twenty-two first-episode, drug-naïve MDD patients were enrolled in the study. These patients received the first taVNS treatment at the baseline time, and underwent resting-state MRI scanning twice, before and after taVNS. All the patients then received taVNS treatments for 4 weeks. The severity of depression was assessed by the 17-item Hamilton Depression Rating Scale (HAMD) at the baseline time and after 4-week's treatment. Pearson analysis was used to assess the correlation between alterations of ReHo and changes of the HAMD scores. Two patients were excluded due to excessive head movement, two patients lack clinical data in the fourth week, thus, imaging analysis was performed in 20 patients, while correlation analysis between clinical and imaging data was performed in only 18 patients. Results: There were significant differences in the ReHo values in first-episode, drug-naïve MDD patients between pre- or post- taVNS. The primary finding is that the patients exhibited a significantly lower ReHo in the left/right median cingulate cortex, the left precentral gyrus, the left postcentral gyrus, the right calcarine cortex, the left supplementary motor area, the left paracentral lobule, and the right lingual gyrus. Pearson analysis revealed a positive correlation between changes of ReHo in the right median cingulate cortex/the left supplementary motor area and changes of HAMD scores after taVNS. Conclusion: The decreased ReHo were found after taVNS. The sensorimotor, limbic and visual-related brain regions may play an important role in understanding the underlying neural mechanisms and be the target brain regions in the further therapy.

Case Report: Delayed Guillain-Barré syndrome following trauma: A case series and manage considerations.

Aim: To analyze clinical associations between Guillain-Barré syndrome (GBS) and trauma. Material and Methods: We retrospectively reviewed the data of eight patients with post-traumatic GBS between July 2011 and December 2018 at the Second Xiangya Hospital, China, and analyzed the triggers, clinical manifestation, examination results, treatment, prognosis, and potential mechanism related to post-traumatic GBS. Results: The included patients had GBS preceded by no risk factors other than trauma. Their age ranged from 15 to 60 years (the median age was 52 years), and six patients were males. The potential traumatic triggers included spinal surgery (n = 2), high-intensity exercise (n = 2), traumatic brain injury (n = 1), excessive fatigue (n = 1), ischemic stroke (n = 1), and cardiopulmonary resuscitation (n = 1). The major manifestation was symmetrical limb weakness and/or numbness in all patients. The diagnosis of GBS was based on the results of electromyography, albumino-cytological dissociation, or antiganglioside antibody in cerebrospinal fluid, and other diseases were excluded. Immunotherapy improved symptoms, except in one patient who died. Conclusions: Trauma is a probable risk factor for GBS that is very easily overlooked, thereby leading to misdiagnosis in clinical practice. We emphasize a new concept of post-traumatic GBS to promote doctors' awareness when they meet people with weakness and sensory deficits after trauma, which benefit early diagnosis, timely treatment, and reduced mortality rate of GBS.

Transformer-Based Deep-Learning Algorithm for Discriminating Demyelinating Diseases of the Central Nervous System With Neuroimaging.

Background: Differential diagnosis of demyelinating diseases of the central nervous system is a challenging task that is prone to errors and inconsistent reading, requiring expertise and additional examination approaches. Advancements in deep-learning-based image interpretations allow for prompt and automated analyses of conventional magnetic resonance imaging (MRI), which can be utilized in classifying multi-sequence MRI, and thus may help in subsequent treatment referral. Methods: Imaging and clinical data from 290 patients diagnosed with demyelinating diseases from August 2013 to October 2021 were included for analysis, including 67 patients with multiple sclerosis (MS), 162 patients with aquaporin 4 antibody-positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD), and 61 patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Considering the heterogeneous nature of lesion size and distribution in demyelinating diseases, multi-modal MRI of brain and/or spinal cord were utilized to build the deep-learning model. This novel transformer-based deep-learning model architecture was designed to be versatile in handling with multiple image sequences (coronal T2-weighted and sagittal T2-fluid attenuation inversion recovery) and scanning locations (brain and spinal cord) for differentiating among MS, NMOSD, and MOGAD. Model performances were evaluated using the area under the receiver operating curve (AUC) and the confusion matrices measurements. The classification accuracy between the fusion model and the neuroradiological raters was also compared. Results: The fusion model that was trained with combined brain and spinal cord MRI achieved an overall improved performance, with the AUC of 0.933 (95%CI: 0.848, 0.991), 0.942 (95%CI: 0.879, 0.987) and 0.803 (95%CI: 0.629, 0.949) for MS, AQP4+ NMOSD, and MOGAD, respectively. This exceeded the performance using the brain or spinal cord MRI alone for the identification of the AQP4+ NMOSD (AUC of 0.940, brain only and 0.689, spinal cord only) and MOGAD (0.782, brain only and 0.714, spinal cord only). In the multi-category classification, the fusion model had an accuracy of 81.4%, which was significantly higher compared to rater 1 (64.4%, p=0.04<0.05) and comparable to rater 2 (74.6%, p=0.388). Conclusion: The proposed novel transformer-based model showed desirable performance in the differentiation of MS, AQP4+ NMOSD, and MOGAD on brain and spinal cord MRI, which is comparable to that of neuroradiologists. Our model is thus applicable for interpretating conventional MRI in the differential diagnosis of demyelinating diseases with overlapping lesions.

White Matter Abnormalities and Cognitive Deficit After Mild Traumatic Brain Injury: Comparing DTI, DKI, and NODDI.

White matter (WM) disruption is an important determinant of cognitive impairment after mild traumatic brain injury (mTBI), but traditional diffusion tensor imaging (DTI) shows some limitations in assessing WM damage. Diffusion kurtosis imaging (DKI) and neurite orientation dispersion and density imaging (NODDI) show advantages over DTI in this respect. Therefore, we used these three diffusion models to investigate complex WM changes in the acute stage after mTBI. From 32 mTBI patients and 31 age-, sex-, and education-matched healthy controls, we calculated eight diffusion metrics based on DTI (fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity), DKI (mean kurtosis), and NODDI (orientation dispersion index, volume fraction of intracellular water (Vic), and volume fraction of the isotropic diffusion compartment). We used tract-based spatial statistics to identify group differences at the voxel level, and we then assessed the correlation between diffusion metrics and cognitive function. We also performed subgroup comparisons based on loss of consciousness. Patients showed WM abnormalities and cognitive deficit. And these two changes showed positive correlation. The correlation between Vic of the splenium of the corpus callosum and Digit Symbol Substitution Test scores showed the smallest p-value (p = 0.000, r = 0.481). We concluded that WM changes, especially in the splenium of the corpus callosum, correlate to cognitive deficit in this study. Furthermore, the high voxel count of NODDI results and the consistency of mean kurtosis and the volume fraction of intracellular water in previous studies and our study showed the functional complementarity of DKI and NODDI to DTI.

Differential Tractography and Correlation Tractography Findings on Patients With Mild Traumatic Brain Injury: A Pilot Study.

Differential tractography and correlation tractography are new tractography modalities to study neuronal changes in brain diseases, but their performances in detecting neuronal injuries are yet to be investigated in patients with mild traumatic brain injury (mTBI). Here we investigated the white matter injury in mTBI patients using differential and correlation tractography. The diffusion MRI was acquired at 33 mTBI patients and 31 health controls. 7 of the mTBI patients had one-year follow-up scans, and differential tractography was used to evaluate injured fiber bundles on these 7 patients. All subjects were evaluated using digital symbol substitution test (DSST) and trail making test A (TMT-A), and the correlation tractography was performed to explore the exact pathways related to the cognitive performance. Our results showed that differential tractography revealed neuronal changes in the corpus callosum in all 7 follow-up mTBI patients with FDR between 0.007 and 0.17. Further, the correlation tractography showed that the splenium of the corpus callosum, combined with the right superior longitudinal fasciculus and right cingulum, were correlated with DSST (FDR = 0.001669) in the acute mTBI patients. The cognitive impairment findings in the acute stage and the longitudinal findings in the corpus callosum in the chronic stage of mTBI patients suggest that differential tractography and correlation tractography are valuable tools in the diagnostic and prognostic evaluation of neuronal injuries in mTBI patients.

Positron emission tomography imaging for the assessment of mild traumatic brain injury and chronic traumatic encephalopathy: recent advances in radiotracers.

A chronic phase following repetitive mild traumatic brain injury can present as chronic traumatic encephalopathy in some cases, which requires a neuropathological examination to make a definitive diagnosis. Positron emission tomography (PET) is a molecular imaging modality that has high sensitivity for detecting even very small molecular changes, and can be used to quantitatively measure a range of molecular biological processes in the brain using different radioactive tracers. Functional changes have also been reported in patients with different forms of traumatic brain injury, especially mild traumatic brain injury and subsequent chronic traumatic encephalopathy. Thus, PET provides a novel approach for the further evaluation of mild traumatic brain injury at molecular levels. In this review, we discuss the recent advances in PET imaging with different radiotracers, including radioligands for PET imaging of glucose metabolism, tau, amyloid-beta, γ-aminobutyric acid type A receptors, and neuroinflammation, in the identification of altered neurological function. These novel radiolabeled ligands are likely to have widespread clinical application, and may be helpful for the treatment of mild traumatic brain injury. Moreover, PET functional imaging with different ligands can be used in the future to perform large-scale and sequential studies exploring the time-dependent changes that occur in mild traumatic brain injury.

Morphometric changes in the cortex following acute mild traumatic brain injury.

Morphometric changes in cortical thickness (CT), cortical surface area (CSA), and cortical volume (CV) can reflect pathological changes after acute mild traumatic brain injury (mTBI). Most previous studies focused on changes in CT, CSA, and CV in subacute or chronic mTBI, and few studies have examined changes in CT, CSA, and CV in acute mTBI. Furthermore, acute mTBI patients typically show transient cognitive impairment, and few studies have reported on the relationship between cerebral morphological changes and cognitive function in patients with mTBI. This prospective cohort study included 30 patients with acute mTBI (15 males, 15 females, mean age 33.7 years) and 27 matched healthy controls (12 males, 15 females, mean age 37.7 years) who were recruited from the Second Xiangya Hospital of Central South University between September and December 2019. High-resolution T1-weighted images were acquired within 7 days after the onset of mTBI. The results of analyses using FreeSurfer software revealed significantly increased CSA and CV in the right lateral occipital gyrus of acute-stage mTBI patients compared with healthy controls, but no significant changes in CT. The acute-stage mTBI patients also showed reduced executive function and processing speed indicated by a lower score in the Digital Symbol Substitution Test, and reduced cognitive ability indicated by a longer time to complete the Trail Making Test-B. Both increased CSA and CV in the right lateral occipital gyrus were negatively correlated with performance in the Trail Making Test part A. These findings suggest that cognitive deficits and cortical alterations in CSA and CV can be detected in the acute stage of mTBI, and that increased CSA and CV in the right lateral occipital gyrus may be a compensatory mechanism for cognitive dysfunction in acute-stage mTBI patients. This study was approved by the Ethics Committee of the Second Xiangya Hospital of Central South University, China (approval No. 086) on February 9, 2019.

Type IIB PKA is highly expressed in ß cells and controls cell proliferation via regulating Cyclin D1 expression.

ß cell number is maintained mainly by cell proliferation and cell apoptosis. Protein kinase A (PKA) pathway is an important intracellular signalling-mediating ß cell proliferation. However, the precise roles of PKA isoforms are not well-defined. We found that the RIIB subunit of PKA is expressed specifically by ß cells of mouse and human islets. Sixty percent pancreatectomy caused increased ß cell proliferation. Deletion of type IIB PKA by disruption of RIIB expression further promoted ß cell proliferation, leading to enhanced ß cell mass expansion. RIIB KO mice also showed increased insulin levels and improved glucose tolerance. Mechanistically, activation of type IIB PKA decreased Cyclin D1 levels and inhibition of RIIB expression increased Cyclin D1 levels. Consistently, activation of type IIB PKA inhibited cell cycle entry. These results suggest that type IIB PKA plays a pivotal role in ß cell proliferation via regulating Cyclin D1 expression.

Trauma-Related Guillain-Barré Syndrome: Systematic Review of an Emerging Concept.

Guillain-Barré syndrome (GBS) is mainly associated with preceding exposure to an infectious agent, although the precise pathogenic mechanisms and causes remain unknown. Increasing evidence indicates an association between trauma-related factors and GBS. Here, we performed a systematic review, summarized the current scientific literature related to the onset of GBS associated with trauma, and explored the possible pathogenesis. A literature search of various electronic databases was performed up to May 2020 to identify studies reporting diverse trauma-related triggers of GBS. Data were extracted, summarized descriptively, and evaluated with respect to possible mechanisms. In total, 100 publications, including 136 cases and 6 case series involving GBS triggered by injury, surgery, intracranial hemorrhage, and heatstroke, met our eligibility criteria. The median age of the patients was 53 [interquartile range (IQR) 45-63] years, and 72.1% of the patients were male. The median number of days between the trigger to onset of GBS symptoms was 9 (IQR 6.5-13). Overall, 121 patients (89.0%) developed post-injury/surgical GBS, whereas 13 (9.6%) and 2 (1.5%) patients had preexisting spontaneous intracranial hemorrhage and heatstroke, respectively. The main locations of injury or surgeries preceding GBS were the spine and brain. Based on available evidence, we highlight possible mechanisms of GBS induced by these triggers. Moreover, we propose the concept of "trauma-related GBS" as a new research direction, which may help uncover more pathogenic mechanisms than previously considered for typical GBS triggered by infection or vaccination.

Herpes Simplex Virus 1-Induced Blood-Brain Barrier Damage Involves Apoptosis Associated With GM130-Mediated Golgi Stress.

Herpes simplex encephalitis (HSE) caused by herpes simplex virus 1 (HSV-1) infection can lead to a high mortality rate and severe neurological sequelae. The destruction of the blood-brain barrier (BBB) is an important pathological mechanism for the development of HSE. However, the specific mechanism underlying the BBB destruction remains unclear. Our previous study found that the Golgi apparatus (GA) plays a crucial role in maintaining the integrity of the BBB. Therefore, this present study aimed to investigate the role of the GA in the destruction of the BBB and its underlying mechanisms. Mouse brain endothelial cells (Bend.3) were cultured to establish a BBB model in vitro, and then infected with HSV-1. The results showed that HSV-1 infection caused downregulation of the Golgi-associated protein GM130, accompanied by Golgi fragmentation, cell apoptosis, and downregulation of tight junction proteins occludin and claudin 5. Knockdown of GM130 with small interfering RNA in uninfected Bend.3 cells triggered Golgi fragmentation, apoptosis, and downregulation of occludin and claudin 5. However, overexpression of GM130 in HSV-1 infected Bend.3 cells by transient transfection partially attenuated the aforementioned damage caused by HSV-1 infection. When the pan-caspase inhibitor Z-VAD-fmk was used after HSV-1 infection to inhibit apoptosis, the protein levels of GM130, occludin and claudin 5 were partially restored. Taken together, these observations indicate that HSV-1 infection of Bend.3 cells triggers a GM130-mediated Golgi stress response that is involved in apoptosis, which in turn results in downregulation of occludin and claudin 5 protein levels. Meanwhile, GM130 downregulation is partially due to apoptosis triggered by HSV-1 infection. Our findings reveal an association between the GA and the BBB during HSV-1 infection and identify potentially novel targets for protecting the BBB and therapeutic approaches for patients with HSE.

A quality assessment of evidence-based guidelines for the prevention and management of ventilator-associated pneumonia: a systematic review.

BACKGROUND: Numerous evidence-based guidelines (EBGs) pertaining to ventilator-associated pneumonia (VAP) have been published by domestic and international organizations, but their qualities have not been reported. METHODS: A systematic search of the literature was performed up to July 2018 for relevant guidelines. Guidelines were eligible for inclusion if they incorporated recommendation statements for prevention and/or management in adults or children with VAP and were developed on a systematic evidence-based method. Four reviewers evaluated each guideline using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument, which comprises 23 items organized into six domains in addition to two overall items. RESULTS: Thirteen EBGs were identified for review. An overall high degree of agreement among reviewers was reached [intra-class correlation coefficient (ICC), 0.885; 95% CI, 0.862-0.905] during their review. The scores (mean, range) for the six AGREE domains were: scope and purpose (61%, 51-74%), stakeholder involvement (36%, 18-68%), rigor of development (41%, 22-59%), clarity and presentation (56%, 47-71%), applicability (38%, 21-59%) and editorial independence (50%, 0-77%). Only two EBGs (15.4%) were rated "recommended" for clinical practice. Approximately 86% of recommendations were based on moderate or low levels of evidence (levels B-D were 46.2%, 19.0%, and 21.2%, respectively). The recommendations for prevention and management of VAP were similar among the different EBGs. CONCLUSIONS: The overall quality of the identified EBGs pertaining to VAP was classified as moderate. The management of VAP varied by guideline. More high-quality evidence is needed to improve guideline recommendations.