Type 2 herpes simplex virus-induced anti-N-methyl-D-aspartate receptor encephalitis responsive to immunoglobulin monotherapy.

Herpes simplex virus-2 encephalitis (HSV2E) in immunocompetent adults is exceptionally rare, and the subsequent onset of autoimmune encephalitis after HSV2E is even less common. This report presents the inaugural Chinese case of anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) induced by HSV2E, confirmed via metagenomic next-generation sequencing (mNGS). The patient demonstrated a favorable response to intravenous immunoglobulin (IVIG) monotherapy. This case emphasizes the importance of considering autoimmune encephalitis in patients exhibiting new or recurrent neurological symptoms after HSV2E recovery. Comprehensive mNGS and neuronal antibody testing are essential for timely diagnosis. Moreover, IVIG monotherapy can serve as an effective treatment for NMDARE induced by HSV2, providing a viable alternative, particularly when steroid therapy is contraindicated.

Biochar addition and reduced irrigation modulates leaf morpho-physiology and biological nitrogen fixation in faba bean-ryegrass intercropping.

Intercropping legume with grass has potential to increase biomass and protein yield via biological N2-fixation (BNF) benefits, whereas the joint effects of biochar (BC) coupled with deficit irrigation on intercropping systems remain elusive. A 15N isotope-labelled experiment was implemented to investigate morpho-physiological responses of faba bean-ryegrass intercrops on low- (550 °C, LTBC) or high-temperature BC (800 °C, HTBC) amended sandy-loam soil under full (FI), deficit (DI) and partial root-zone drying irrigation (PRD). LTBC and HTBC significantly reduced intrinsic water-use efficiency (WUE) by 12 and 14 %, and instantaneous WUE by 8 and 16 %, respectively, in faba bean leaves, despite improved photosynthetic (An) and transpiration rate (Tr), and stomatal conductance (gs). Compared to FI, DI and PRD lowered faba bean An, gs and Tr, but enhanced leaf-scale and time-integrated WUE as proxied by the diminished shoots Δ13C. PRD enhanced WUE as lower gs, Tr and guard cell length than DI-plants. Despite higher carbon ([C]) and N concentration ([N]) in faba bean shoots amended by BC, the aboveground C- and N-pool of faba bean were reduced, while these pools increased for ryegrass. The N-use efficiency (NUE) in faba bean shoots was reduced by 9 and 14 % for LTBC and HTBC, respectively, but not for ryegrass. Interestingly, ryegrass shoots had 52 % higher NUE than faba bean shoots. The N derived from atmosphere (% Ndfa) was increased by 2 and 9 % under LTBC and HTBC, respectively, while it decreased slightly by reduced irrigation. Quantity of BNF in faba bean aboveground biomass decreased with HTBC coupled with reduced irrigation, mainly towards decreased biomass and soil N uptake by faba bean. Therefore, HTBC might not be a feasible option to improve WUE and BNF in faba bean-ryegrass intercropping, but PRD is permissible as the clear trade-off between BC and PRD.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): contemporary advances and current controversies.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory syndrome with characteristic clinical, radiological, and pathological features, and can be effectively treated with corticosteroid-based immunotherapies. The exact pathogenesis of CLIPPERS remains unclear, and specific diagnostic biomarkers are not available. According to the 2017 diagnostic criteria, probable CLIPPERS should be considered in middle-aged patients with subacute onset of pontocerebellar symptoms and typical punctuate and curvilinear gadolinium enhancement lesions ("salt-and-pepper" appearance) located in the hindbrain (especially pons) on magnetic resonance imaging. In addition, CLIPPERS-mimics, such as central nervous system (CNS) lymphoma, and several antibody-associated autoimmune CNS diseases (e.g., myelin oligodendrocyte glycoprotein antibody-associated disease, autoimmune glial fibrillary acidic protein astrocytopathy, and anti-N-methyl-D-aspartate receptor encephalitis), should be extensively excluded. The prerequisite for definite CLIPPERS is the perivascular T-cell-predominant inflammatory infiltration observed on pathological analysis. A biopsy is strongly suggested when clinical/radiological red flags are present. Most patients with CLIPPERS respond well to corticosteroids and have a good prognosis. Long-term low-dose corticosteroid maintenance therapy or corticosteroids coupled with immunosuppressants are recommended to prevent the recurrence of the syndrome. The potential progression of CLIPPERS to lymphoma has been suggested in some cases; therefore, at least 2-year clinical and radiological follow-up is essential. Here, we critically review the recent developments and provided an update on the clinical characteristics, diagnostic criteria, differential diagnoses, and therapeutic management of CLIPPERS. We also discuss the current controversies in this context that can be resolved in future research studies.

Myelin oligodendrocyte glycoprotein antibody and N-methyl-d-aspartate receptor antibody overlapping syndrome: insights from the recent case reports.

The overlapping of two or more types of neural autoantibodies in one patient has increasingly been documented in recent years. The coexistence of myelin oligodendrocyte glycoprotein (MOG) and N-methyl-d-aspartate receptor (NMDAR) antibodies is most common, which leads to a unique condition known as the MOG antibody and NMDAR antibody overlapping syndrome (MNOS). Here, we have reviewed the pathogenesis, clinical manifestations, paraclinical features, and treatment of MNOS. Forty-nine patients with MNOS were included in this study. They were young males with a median onset age of 23 years. No tumors were observed in the patients, and 24 of them reported prodromal symptoms. The most common clinical presentations were psychiatric symptoms (35/49) and seizures (25/49). Abnormalities on magnetic resonance imaging involved the brainstem (11/49), cerebellum (9/49), and parietal lobe (9/49). Most patients mostly responded to immunotherapy and had a good long-term prognosis. However, the overall recurrence rate of MNOS was higher than that of mono antibody-positive diseases. The existence of concurrent NMDAR antibodies should be suspected in patients with MOG antibody-associated disease having psychiatric symptoms, seizures, movement disorders, or autonomic dysfunction. Similarly, serum MOG antibody testing should be performed when patients with anti-NMDAR encephalitis present with atypical clinical manifestations, such as visual impairment and limb weakness, and neuroradiological findings, such as optic nerve, spinal cord, or infratentorial involvement or meningeal enhancement. Early detection of the syndrome and prompt treatment can be beneficial for these patients, and maintenance immunosuppressive therapy is recommended due to the high overall recurrence rate of the syndrome.

Anti-adenylate kinase 5 encephalitis: Clinical characteristics, diagnosis, and management of this rare entity.

The spectrum and understanding of antibody-positive autoimmune encephalitis (AE) have expanded over the past few decades. In 2007, a rare subtype of AE known as anti-adenylate kinase 5 (AK5) encephalitis, was first reported. This disease is more common in elderly males, with limbic encephalitis as the core phenotype (characterized by subacute anterograde amnesia, sometimes with psychiatric symptoms, and rarely with seizures). Brain magnetic resonance imaging typically demonstrated initial temporal lobe T2/fluid-attenuated inversion recovery hyperintensities, and subsequent atrophy. No concomitant tumors have been found yet. AK5 antibody, targeting the intracellular antigen, is a biomarker for a non-paraneoplastic T-cell autoimmunity response, and can be detected in serum and cerebrospinal fluid using tissue-based and cell-based assays. Cytotoxic T-cell-mediating neuronal injury and loss play a pivotal role in the immunopathogenesis of anti-AK5 encephalitis. Patients mostly show poor response to immunotherapy and thus a poor prognosis in the long run. Herein, we review the literature and provide updated knowledge of this less-known entity, focusing on clinical characteristics, paraclinical findings, diagnosis process, and therapeutic approaches.

S100A family is a group of immune markers associated with poor prognosis and immune cell infiltration in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common human cancers with poor prognosis in the world. HCC has become the second leading cause of cancer-related death in China. It is urgent to identify novel biomarker and valid target to effectively diagnose, treat or predict the prognosis of HCC. It has been reported that S100A family is closely related to cell proliferation and migration of different cancers. However, the values of S100As in HCC remain to be further analyzed. METHODS: We investigated the transcriptional and translational expression of S100As, as well as the value of this family in HCC patients from the various databases. RESULTS: S100A10 was most relevant to HCC. CONCLUSIONS: The results from HCC patients' tissues and different cells also confirmed the role of S100A10 in HCC. Furthermore, we proved that S100A10 could influenced the cell proliferation of HCC cells via ANXA2/Akt/mTOR pathway. However, it would appear that the relationship between S100A10 and HCC is complex and requires more research.

Myelin oligodendrocyte glycoprotein antibody-associated disease preceding primary central nervous system lymphoma: causality or coincidence?

INTRODUCTION: Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphomatous malignancy that affects the brain, spinal cord, leptomeninges, or eyes, in the absence of systemic diffusion. Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a newly identified benign immune-mediated CNS inflammatory disorder with specific anti-MOG antibody seropositivity. These two seemingly unrelated nosological entities both have abundant clinical and radiological manifestations, and whether there is a potential link between them is unclear. CASE REPORT: We describe a 49-year-old man who presented progressive headache, dizziness, and unsteady gait with multifocal scattered T2 hyperintensities with contrast enhancement. The serum anti-MOG antibody test was positive, and a brain biopsy showed inflammatory infiltration. Initially, he was diagnosed with MOGAD and his condition improved after corticosteroid therapy. The patient relapsed with exacerbation of symptoms and neuroimaging showed new mass-forming lesions four months later. A second brain biopsy confirmed PCNSL. DISCUSSION: This is the first report of histologically confirmed successive MOGAD and PCNSL. Our case broadens the phenotypic spectrum of sentinel lesions in PCNSL. Though rare, PCNSL should be considered in patients diagnosed with benign CNS inflammatory disorder and responding well to steroid treatment when their clinical symptoms worsen and the imaging deteriorates. A timely biopsy is critical for accurate diagnosis and appropriate therapy.

Illuminating and Radiosensitizing Tumors with 2DG-Bound Gold-Based Nanomedicine for Targeted CT Imaging and Therapy.

Although radiotherapy is one of the most important curative treatments for cancer, its clinical application is associated with undesired therapeutic effects on normal or healthy tissues. The use of targeted agents that can simultaneously achieve therapeutic and imaging functions could constitute a potential solution. Herein, we developed 2-deoxy-d-glucose (2DG)-labeled poly(ethylene glycol) (PEG) gold nanodots (2DG-PEG-AuD) as a tumor-targeted computed tomography (CT) contrast agent and radiosensitizer. The key advantages of the design are its biocompatibility and targeted AuD with excellent sensitivity in tumor detection via avid glucose metabolism. As a consequence, CT imaging with enhanced sensitivity and remarkable radiotherapeutic efficacy could be attained. Our synthesized AuD displayed linear enhancement of CT contrast as a function of its concentration. In addition, 2DG-PEG-AuD successfully demonstrated significant augmentation of CT contrast in both in vitro cell studies and in vivo tumor-bearing mouse models. In tumor-bearing mice, 2DG-PEG-AuD showed excellent radiosensitizing functions after intravenous injection. Results from this work indicate that 2DG-PEG-AuD could greatly potentiate theranostic capabilities by providing high-resolution anatomical and functional images in a single CT scan and therapeutic capability.

An ultrasound-based radiomics model for survival prediction in patients with endometrial cancer.

PURPOSE: To establish a nomogram integrating radiomics features based on ultrasound images and clinical parameters for predicting the prognosis of patients with endometrial cancer (EC). MATERIALS AND METHODS: A total of 175 eligible patients with ECs were enrolled in our study between January 2011 and April 2018. They were divided into a training cohort (n = 122) and a validation cohort (n = 53). Least absolute shrinkage and selection operator (LASSO) regression were applied for selection of key features, and a radiomics score (rad-score) was calculated. Patients were stratified into high risk and low-risk groups according to the rad-score. Univariate and multivariable COX regression analysis was used to select independent clinical parameters for disease-free survival (DFS). A combined model based on radiomics features and clinical parameters was ultimately established, and the performance was quantified with respect to discrimination and calibration. RESULTS: Nine features were selected from 1130 features using LASSO regression in the training cohort, which yielded an area under the curve (AUC) of 0.823 and 0.792 to predict DFS in the training and validation cohorts, respectively. Patients with a higher rad-score were significantly associated with worse DFS. The combined nomogram, which was composed of clinically significant variables and radiomics features, showed a calibration and favorable performance for DFS prediction (AUC 0.893 and 0.885 in the training and validation cohorts, respectively). CONCLUSION: The combined nomogram could be used as a tool in predicting DFS and may assist individualized decision making and clinical treatment.

Vascular endothelial growth factor A is a potential prognostic biomarker and correlates with immune cell infiltration in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths among cancer patients. Vascular endothelial growth factor A (VEGFA) is involved in regulating biological processes, such as angiogenesis and vascular permeability, and is very closely related to the pathogenesis of various tumours, especially vascular-rich, solid tumours. Clinical data of patients with HCC and other tumours were analysed through public databases, such as the TCGA database, Gene Expression Omnibus database, Human Protein Atlas database, STRING, Tumour Immune Estimation Resource and Kaplan-Meier Plotter. The tumour tissues and adjacent normal tissues of patients with HCC from Hunan Provincial People's Hospital were collected to verify the expression of VEGFA by immunohistochemistry, immunofluorescence, Western blotting and qPCR. VEGFA expression is elevated in multiple tumour types and correlates with the prognosis of tumour patients. VEGFA is involved in regulating the tumour microenvironment and immune cell function in tumour development. Inhibition of VEGFA reduces proliferation, invasion, and migration and promotes apoptosis in HCC cells. VEGFA is a potential predictive biomarker for the diagnosis and prognosis of HCC.

MS/MS molecular networking-guided in-depth profiling of triterpenoid saponins from the fruit of Eleutherococcus senticosus and their neuroprotectivity evaluation.

INTRODUCTION: Eleutherococcus senticosus fruit (ESF) is a natural health supplement resource that has been extensively applied as a tonic for the nervous system. The structures and neural bioactivities of triterpenoid saponins (TS), which are the major constituents of ESF, have not been comprehensively analyzed thus far. OBJECTIVE: We conducted a complete in-depth MS/MS molecular networking (MN)-based targeted analysis of TS from the crude extract of ESF and investigated its neuroprotective value. METHODS: An MS/MS MN-guided strategy was used to rapidly present a series of precursor ions (PIs) of TS in a compound cluster as TS-targeted information used in the discovery and characterization of TS. In addition, a prepared TS-rich fraction of ESF was assayed for its restraining effects on ß-amyloid-induced inhibition of neurite outgrowth. RESULTS: A total of 87 TS were discovered using a PI tracking strategy, 28 of which were characterized as potentially undescribed structures according to their high-resolution MS values. Furthermore, the TS-rich fraction can significantly reduce ß-amyloid-induced damage to neural networks by promoting the outgrowth of neurites and axons. CONCLUSION: Our findings reveal the richness of TS in ESF and will accelerate their application in the treatment of neurodegenerative diseases.

Identification and localization of morphological feature-specific metabolites in Reynoutria multiflora roots.

Reynoutria multiflora roots are a classical herbal medicine with unique nourishing therapeutic effects. Anomalous vascular bundle (AVB) forming "cloudy brocade patterns" is a typical morphological feature of R. multiflora roots and has been empirically linked to its quality classification. However, scientific evidence, especially for AVB-specific specialised metabolites, has not been comprehensively revealed thus far. Herein, desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) analysis was applied to carry out an in situ analysis of specialised metabolites distributed specifically at the AVB and cork of R. multiflora roots. To enlarge the scope of compounds by DESI detection, various solvent systems including acetone, acetonitrile, methanol, and water were used to assist in the discoveries of 40 specialised metabolites with determined localization. A series of bioactive constituents including stilbenes, flavonoids, anthraquinones, alkaloids, and naphthalenes were found specifically around the brocade patterns. Notably, phospholipids were detected from R. multiflora roots by in situ analysis for the first time and were found mainly in the phloem of AVB (PAB). This is the first study to use gradient solvent systems in DESI-MSI analysis to locate the specialised metabolites distribution. The discovery of feature-specific compounds will bridge the empirical identification to precision quality control of R. multiflora roots.

Phenotyping the late- and younger-onset neuronal surface antibody-mediated autoimmune encephalitis: a multicenter study.

Neuronal surface antibody-mediated autoimmune encephalitis (NSAE) occurs across a wide age range. However, few studies focused on the onset age and their related characteristics. We aimed to explore the age-dependent profile of NSAE. A total of 134 patients with a definite diagnosis of NSAE were retrospectively enrolled from 3 tertiary hospitals between July 2014 and August 2020. Demographic, clinical, therapeutic, and prognostic data were collected and compared between the late- (≥45) and younger-onset (<45) groups. The results showed that 56 (41.8%) patients were classified as late-onset NSAE, and 78 (58.2%) as younger-onset NSAE. There were more males, especially in the late-onset group (P = 0.036). Prodromal symptoms were more common in the younger-onset group (P = 0.004). Among the onset symptoms, more late-onset patients presented as seizures, while more younger-onset patients presented as psychiatric symptoms. Throughout the disease course, the late-onset patients were more likely to have memory dysfunction (P < 0.001), but less likely to have central hypoventilation (P = 0.045). The late-onset patients also had a significantly lower modified Rankin Scale score on admission (P = 0.042), required intensive care unit (ICU) admission less frequently during hospitalization (P = 0.042) and had a shorter hospital stay (P = 0.014). Our study revealed that the late- and younger-onset NSAE had a distinct spectrum of demographic features, presentations, and prognoses. More attention is needed for the younger-onset patients, given a higher disease severity on admission, more frequent requirement for ICU admission and longer length of stay.

Management of epilepsy in pregnancy in eastern China: A survey from the Zhejiang association against epilepsy.

Objective: We aimed to evaluate the knowledge of the board members of the Zhejiang Association Against Epilepsy (ZAAE) regarding pregnancy of women with epilepsy (WWE), as well as their clinical practice and obstacles in the management of WWE. Methods: A cross-sectional survey was conducted among the board members of the ZAAE using a questionnaire based on the management guidelines for WWE during pregnancy in China. We recorded the demographic characteristics of the surveyed practitioners, the coincidence rate of each question, clinical practice, and the barriers encountered in managing WWE. Results: This survey showed that the average knowledge score of the surveyed practitioners was 71.02%, and the knowledge score of neurologists was higher than that of neurosurgeons. Knowledge regarding the following three aspects was relatively poor: whether WWE is associated with an increased risk of cesarean section and preterm delivery, the preferred analgesic drugs for WWE during delivery, and the time of postpartum blood concentration monitoring. After multiple linear regression analysis, the score of neurologists was correlated to the number of pregnant WWE treated each year. In addition, the biggest difficulty in the management of WWE during pregnancy is the lack of patient education and doctors training on pregnant epilepsy management. Conclusion: Our study revealed the ZAAE board members' knowledge and management status of pregnant WWE. In addition, our study identified the biggest obstacle to the management of WWE during pregnancy, and emphasized the importance of training and practice of epilepsy knowledge during pregnancy for practitioners and the significance of interdisciplinary communication.

Boosting the potassium-ion storage performance enabled by engineering of hierarchical MoSSe nanosheets modified with carbon on porous carbon sphere.

Developing suitable electrode materials capable of tolerating severe structural deformation and overcoming sluggish reaction kinetics resulting from the large radius of potassium ion (K+) insertion is critical for practical applications of potassium-ion batteries (PIBs). Herein, a superior anode material featuring an intriguing hierarchical structure where assembled MoSSe nanosheets are tightly anchored on a highly porous micron-sized carbon sphere and encapsulated within a thin carbon layer (denoted as Cs@MoSSe@C) is reported, which can significantly boost the performance of PIBs. The assembled MoSSe nanosheets with expanded interlayer spacing and rich anion vacancy can facilitate the intercalation/deintercalation of K+ and guarantee abundant active sites together with a low K+ diffusion barrier. Meanwhile, the thin carbon protective layer and the highly porous carbon sphere matrix can alleviate the volume expansion and enhance the charge transport within the composite. Under these merits, the as-prepared Cs@MoSSe@C anode exhibits a high reversible capacity (431.8 mAh g-1 at 0.05 A g-1), good rate capability (161 mAh g-1 at 5 A g-1), and superior cyclic performance (70.5% capacity retention after 600 cycles at 1 A g-1), outperforming most existing Mo-based S/Se anodes. The underlying mechanisms and origins of superior performance are elucidated by a set of correlated in-situ/ex-situ characterizations and theoretical calculations. Further, a PIB full cell based on Cs@MoSSe@C anode also exhibits an impressive electrochemical performance. This work provides some insights into developing high-performance PIBs anodes with transition-metal chalcogenides.

Evaluation of CSF albumin quotient in neuronal surface antibody-associated autoimmune encephalitis.

BACKGROUND AND OBJECTIVES: Disruption of brain barriers is considered to be involved in the pathogenesis of neuronal surface antibody-associated autoimmune encephalitis (NSAE), but few studies have focused on their relationship. We aimed to explore the association between the integrity of brain barriers and clinical and paraclinical characteristics in patients with NSAE. METHODS: This retrospective study consecutively recruited patients with NSAE. The cerebrospinal fluid (CSF) / serum albumin quotient (Qalb) was used to evaluate the function of brain barriers. The data on demographic information, clinical manifestations, magnetic resonance imaging (MRI), CSF findings and prognosis were collected and analyzed. RESULTS: Of the 93 patients included, 33 (35.5%) patients were assigned to the elevated Qalb group and 60 (64.5%) patients to the normal Qalb group. Males and prodromal symptoms were more common in elevated Qalb group (both P < 0.05). The CSF white blood cell, protein, immunoglobulin G and albumin were significantly higher in elevated Qalb group (all P < 0.05). Patients with elevated Qalb were more likely to have brain lesions on MRI (60.6% versus 33.3%, P = 0.011). The modified Rankin Scale (mRS) scores at discharge and at last follow-up were significantly higher in patients with elevated Qalb than those with normal Qalb (both P < 0.05). After univariate and multivariate analyses, Qalb elevation (adjusted odds ratio = 3.96, 95% confidence interval = 1.15-13.59, P = 0.029) was demonstrated as the only independent risk factor for a poor prognosis. DISCUSSION: Males, prodromal symptoms, brain lesions on MRI, CSF pleocytosis, and elevated CSF protein were more common in NSAE patients with increased Qalb. Qalb elevation was an independent prognostic indicator for a poor prognosis in NSAE.

Detecting vulnerable carotid plaque and its component characteristics: Progress in related imaging techniques.

Carotid atherosclerotic plaque rupture and thrombosis are independent risk factors for acute ischemic cerebrovascular disease. Timely identification of vulnerable plaque can help prevent stroke and provide evidence for clinical treatment. Advanced invasive and non-invasive imaging modalities such as computed tomography, magnetic resonance imaging, intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy can be employed to image and classify carotid atherosclerotic plaques to provide clinically relevant predictors used for patient risk stratification. This study compares existing clinical imaging methods, and the advantages and limitations of different imaging techniques for identifying vulnerable carotid plaque are reviewed to effectively prevent and treat cerebrovascular diseases.