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Objective: The objective of this study was to investigate the factors influencing relapse and prognosis in patients with primary autoimmune cerebellar ataxia (PACA), an area previously not well understood., Methods: This prospective cohort study included patients who satisfied the modified diagnostic criteria of PACA. A modified Rankin scale score ≤ 2 at the last follow-up was defined as a favorable prognosis. Cox and Logistic regression were utilized to identify relapsing and prognostic factors, respectively., Results: A total of 68 patients were included and 35.3% were male. The median onset age was 42.9 years (IQR 22.1-54.0). Neuronal autoantibodies were detected in 33 (50.8%) patients. Of the 65 patients who received first-line immunotherapy, 55 (84.6%) were responsive and 10 (15.4%) were not. Responsiveness to first-line immunotherapy emerged as an independent factor for favorable prognosis (HR 16.762; 95% CI 2.877-97.655; p = 0.002), as did the absence of peripheral neuropathy/radiculopathy (HR 14.286; 95% CI 2.41-83.333; p = 0.003). Relapses occurred in 19 (27.9%) patients. Onset age ≤ 43 years (HR 5.245; 95% CI 1.499-18.35; p = 0.009), presence of peripheral neuropathy/radiculopathy (HR 4.280; 95% CI 1.622-11.298; p = 0.003) and elevated cerebrospinal fluid (CSF) protein concentration (HR 3.443; 95% CI 1.083-10.951; p = 0.036) were statistically significant relapsing factors., Conclusion: This study identified younger onset age, presence of peripheral neuropathy/radiculopathy and elevated CSF protein concentration as relapsing factors, and absence of peripheral neuropathy/radiculopathy and responsiveness to first-line immunotherapy as independent factors for favorable prognosis in PACA patients. These findings may guide individualized treatment strategies and potentially improve patient outcomes., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

According to recent research, metabolic-associated fatty liver disease (MAFLD) has emerged as an important underlying etiology of hepatocellular carcinoma (HCC). However, the molecular mechanism of MAFLD-HCC is still unclear. Tumor necrosis factor receptor-associated factor 2 (TRAF2) is the key molecule to mediate the signal of inflammatory NF-κB pathway. This study aims to investigate the potential dysregulation of TRAF2 and its biological function in MAFLD-HCC. Huh7 TRAF2 -/- demonstrated increased tumor formation ability compared to huh7 TRAF2 +/+ when stimulated with transforming growth factor-β (TGF-β). The decisive role of TGF-β in the development of MAFLD-HCC was confirmed through the specific depletion of TGF-β receptor II gene in the hepatocytes (Tgfbr2ΔHep) of mice. In TRAF2 -/- cells treated with TGF-β, both the glycolysis rate and lipid synthesis were enhanced. We proved the signal of the mechanistic target of rapamycin complex 1 (mTORC1) could be activated in the presence of TGF-β, and was enhanced in TRAF2 -/- cells. The coimmunoprecipitation (co-IP) experiments revealed that TRAF2 fortified the Smurf2-mediated ubiquitination degradation of AXIN1. Hence, TRAF2 depletion resulted in increased Smad7 degradation induced by AXIN1, thus promoting the TGF-β signal. We also discovered that PLX-4720 could bind with AXIN1 and restrained the tumor proliferation of TRAF2 -/- in mice fed with high-fat diet (HFD). Our findings indicate that TRAF2 plays a significant role in the pathogenesis of MAFLD-HCC. The reduction of TRAF2 expression leads to the enhancement of the TGF-β-mTORC1 pathway by facilitating AXIN1-mediated Smad7 degradation., (© 2024 Federation of American Societies for Experimental Biology.)

Objective: This study aims to explore the factors influencing Chinese parents' attitudes toward death education. Given the current lack of such education in China, this research is particularly significant. Death education is vital for shaping the values of young people and alleviating mental health issues, such as depression and suicidal tendencies. By identifying these influencing factors, this study seeks to provide guidance for policymakers and educators in promoting the development and widespread adoption of death education., Methods: To do so, a national cross-sectional quota sample of 12,435 Chinese parents was used. Borrowing from social-ecological theory, the researchers carried out multiple stepwise regression analyses to examine the individual, family, and social-level factors that shape the supportive attitudes of Chinese parents toward death education., Results: The findings revealed that at the individual level, parent ( β  = 0.04, p  < 0.001), education level ( β  = 0.07, p  < 0.001), and religious belief ( β  = -0.02, p  < 0.05) were significant predictors of Chinese parents' support for death education. Meanwhile, at the family and social level, average monthly household income ( β  = 0.07, p  < 0.001), family health ( β  = 0.03, p  < 0.05), family communication ( β  = 0.02, p  < 0.05), social support ( β  = 0.15, p  < 0.001), neighborhood relations ( β  = 0.11, p  < 0.001), and social network size ( β  = 0.05, p  < 0.001) were significant predictors of Chinese parents' supportive attitudes toward death education., Conclusion: Based on these findings, it is suggested that the relevant development, planning, publicity, and public welfare groups and government departments should promote death education, provide more social support, and encourage neighborhood harmony. As higher education and average monthly household income were found to significantly impact the support, the government should improve access to higher education and actively work to increase residents' income to facilitate the development of death education., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Xiao, Huang, Fan, Wu, Li and Wu.)

Background: Autoantibodies are useful biomarkers for the early detection and diagnosis of autoimmune cerebellar ataxia (ACA)., Objective: To identify novel autoantibody candidates in ACA patients., Methods: Patients with cerebellar ataxia of unknown cause were recruited from July 2018 to February 2023. Anti-neural autoantibodies in patient samples were detected by tissue-based indirect immunofluorescence assay (TBA) on rat cerebellum sections. TBA-positive samples were further screened for well-established anti-neural autoantibodies using commercial kits. Tissue-immunoprecipitation (TIP) and subsequent mass spectrometric (MS) analysis were used to explore the target antigens of autoantibodies in samples that were TBA-positive but negative for known autoantibodies. The specific binding between autoantibodies and the identified target antigen was confirmed by neutralization experiments, recombinant cell-based indirect immunofluorescence assay (CBA), and western blotting experiments., Results: The eukaryotic translation elongation factor 1 delta (EEF1D) protein was identified as a target antigen of autoantibodies in samples from a 43-year-old female ACA patient, while the specific binding of autoantibodies and EEF1D was confirmed by subsequent experiments. A second anti-EEF1D autoantibody-positive ACA patient, a 59-year-old female, was detected in simultaneous screening. The main clinical manifestations in each of the two patients were cerebellar syndrome, such as unsteady walking and limb ataxia. Both patients received immunotherapy, including corticosteroids, intravenous immunoglobulin, and mycophenolate mofetil. Their outcomes provided evidence to support the effectiveness of immunotherapy, but the cerebellar atrophy that occurred before treatment may be irreversible., Conclusion: In the current study, we identified anti-EEF1D autoantibody as a novel autoantibody candidate in ACA. Its pathological roles and diagnostic value need to be further verified in larger-scale studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Guo, Ren, Fan, Chao, Liu, Guan and Wang.)

Background: Mycophenolate mofetil (MMF) is frequently used in the treatment of neurological autoimmune disorders. However, its effect on the relapse risk in anti-leucine-rich glioma-inactivated protein 1 (anti-LGI1) encephalitis is not well studied., Methods: In this prospective observational cohort study, anti-LGI1 encephalitis patients were grouped according to MMF treatment status (MMF and non-MMF groups). The primary outcome was relapse after disease onset., Results: A total of 83 patients were included, with a median onset age of 60 years. Fifty-four patients were men (65.1%). The MMF group comprised 28 patients and the non-MMF group comprised 55. Median follow-up from symptom onset was 26 months. Relapse occurred in 43 patients (51.8%). Median modified Rankin scale (mRS) score at enrollment was significantly higher in the MMF group than the non-MMF group (3 vs. 2; p = 0.001). Median mRS score at last follow-up was comparable between groups (1 vs. zero; p = 0.184). Both MMF treatment (HR 0.463; 95% CI, 0.231-0.929; p = 0.030) and cognitive impairment at enrollment (HR 3.391; 95% CI, 1.041-11.044; p = 0.043) were independent predictors of relapse. Starting immunotherapy before development of cognitive impairment trended towards reducing relapse risk. Outcome at last follow-up was good (mRS score 0-2) in all patients except for one in the non-MMF group. Adverse events associated with MMF treatment were mild and transient., Conclusion: Although the outcome of anti-LGI1 encephalitis patients is generally favorable, relapse is common, especially in those with cognitive impairment. MMF treatment is well-tolerated and can significantly reduce the risk of relapse., (© 2023. Fondazione Società Italiana di Neurologia.)

The aim of this study is to analyze the clinical characteristics and outcomes of Chinese patients with progressive multifocal leukoencephalopathy (PML) who were treated with programmed cell death protein 1 (PD1) blockade therapies. We retrospectively analyzed patients who were admitted to our hospital between October 1, 2020, and October 1, 2022, diagnosed with PML and treated with PD1 blockade therapies. Four patients with PML who were treated with PD1 blockade therapies were identified. All patients were male, and their ages ranged from 19 to 54 years old. One patient (Case 2) exhibited mild pleocytosis, while three patients (Cases 2-4) had markedly reduced T lymphocyte cell counts prior to treatment. The time interval between symptom onset and treatment initiation ranged from six to 54 weeks. All patients received pembrolizumab treatment, with a total of two to four doses administered. Three patients who responded to pembrolizumab treatment showed clinical improvement starting around 8 weeks after the initiation of therapy. Although one patient did not show clinical improvement, they ultimately survived until the last follow-up. None of the patients in this study exhibited immune-related adverse events or immune reconstitution inflammatory syndrome. PD1 blockade appears to be a promising novel therapeutic option for PML; additional prospective studies are necessary to confirm its efficacy., (© 2023. The Author(s) under exclusive licence to The Journal of NeuroVirology, Inc.)

The gas gap of a multi-gap gas switch can be classified as trigger and self-breakdown gaps based on the breakdown condition. A two-gap gas switch consisting of a trigger gap and a self-breakdown gap is developed to independently study the breakdown characteristics of these two types of switch gaps. Trigger experiments for the switch are conducted under various trigger voltage rise rates and different working coefficients. The experimental results indicate that the trigger gap has significantly more jitter than the self-breakdown gap, and the overall performance of the gas switch is determined primarily by the trigger gap. A novel pre-ionization structure with disks is implemented into the two-gap gas switch, considerably decreasing the breakdown delay of the trigger gap and reducing the jitter to a quarter or even less compared to that without pre-ionization. A calculation model of the breakdown time delay for the trigger gap is provided based on the foundational development of the avalanche. The probability distribution of the time required for the initial electron generation is derived in the absence of pre-ionization. The calculated breakdown time delay agrees well with the experimental results in cases with and without pre-ionization under most trigger settings. The method and principle of calculating the breakdown time delay can analyze the collapse of a gas gap with different electrode configurations (quasi-uniform or uniform electrical fields) and various gas media under a nanosecond pulse voltage., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Objective: Our study aimed to investigate the utility of 18 F-FDG PET imaging in diagnosing and monitoring patients with anti-leucine-rich glioma-inactivated 1 antibody autoimmune encephalitis (anti-LGI1 AE). We also sought to understand the mechanisms of faciobrachial dystonic seizures (FBDSs)., Patients and Methods: We analyzed 18 F-FDG PET scans from 50 patients with anti-LGI1 AE, using visual and semiquantitative methods, and compared these with 24 healthy controls. All patients tested positive for anti-LGI1 antibodies in serum or cerebrospinal fluid before PET imaging. The patients were divided into FBDS and non-FBDS groups to compare metabolic differences using voxel-based semiquantitative analysis. Finally, we separately analyzed PET images of patients with symptom recurrence., Results: The sensitivity of 18 F-FDG PET was superior to MRI (97.9% vs 63.8%, respectively; P < 0.001). Semiquantitative analysis revealed hypermetabolism in the basal ganglia, medial temporal lobe, and brainstem, and hypometabolism in most neocortical regions compared with healthy controls. The FBDS group exhibited hypometabolism in the frontal and temporal lobes compared with the non-FBDS group. Among 7 recurrent patients, 3 were confirmed as recurrence and 3 as sequelae by PET. One patient relapsed shortly after discontinuing corticosteroids when PET indicated active lesions., Conclusions: 18 F-FDG PET scans were more sensitive than MRI in detecting anti-LGI1 AE, which displayed a pattern of hypermetabolism in the basal ganglia and medial temporal lobe, as well as neocortex hypometabolism. Hypometabolism in the frontal and temporal lobes was associated with FBDS. Furthermore, 18 F-FDG PET scans can differentiate recurrence from sequelae and guide the timing of immunotherapy cessation., Competing Interests: Conflicts of interest and sources of funding: This work was financially supported by a grant (2022-PUMCH-B-070) from the National High Level Hospital Clinical Research Funding. All authors involved in this work have declared no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

CD9 is a member of the tetraspanin protein family, which has been widely studied in inflammation and cancer, but not in pathological cardiac hypertrophy. In this study, we found that the expression of CD9 was increased in transaortic constriction (TAC) myocardial tissue. Knockdown of CD9 alleviated damage to cardiac function in the TAC model and reduced heart weight, cardiomyocyte size, and degree of fibrosis, and vice versa. Mechanistically, co-immunoprecipitation results showed that CD9 and GP130 can bind to each other in cardiomyocytes, and knockdown of CD9 can reduce the protein level of GP130 and the phosphorylation of STAT3 in vivo and in vitro , and vice versa. GP130 knockdown reversed the aggravating effects of CD9 on pathological cardiac hypertrophy. Therefore, we conclude that CD9 exacerbates pathological cardiac hypertrophy by regulating the GP130/STAT3 signaling pathway and may serve as a therapeutic target for pathological cardiac hypertrophy., Competing Interests: The authors declare that they have no competing interests., (© 2023 The Authors.)

Background: Aflibercept has been approved for the treatment of metastatic colorectal cancer for more than a decade, but its antiangiogenesis adverse effect profile during treatment remains unclear. This study is conducted to systematically review the risk of antiangiogenic adverse events in patients with metastatic colorectal cancer receiving aflibercept plus chemotherapy., Methods: We searched databases, including PubMed, Embase and the Cochrane Library up to September 9, 2021. Relevant randomized controlled trials (RCTs) and single-arm studies were included in the review. Statistical analyses were performed using R to calculate the summary incidence rate of antiangiogenic-related adverse events, odds ratios and 95% CIs. Heterogeneity among the included studies was assessed by subgroup analysis. Publication bias analysis and sensitivity analysis were performed to confirm the reliability of the results., Results: A total of 2889 patients from 10 studies met the inclusion criteria. The quality of the included studies was evaluated as qualified for further quantitative synthesis. In part of single-arm studies, the occurrence rates were 44.2% (95%CI, 39.7-48.7%) for hypertension, 31.3% (95% CI, 19.3-43.3%) for proteinuria, 27.3% (95%CI, 21.2-33.4%) for epistaxis, 22.5% (95%CI, 7.8-37.3%) for hemorrhage events, 8.0% (95%CI, 2.0-14 .0%) for venous thromboembolic event in all grades and 22.6% (95%CI, 19.1-26.2%) for grade III/IV hypertension, 7.4% (95%CI, 6.2-8.5%) for grade III/IV proteinuria. In part of RCT, compared to its counterpart, aflibercept containing arm was associated with the increased incidence rate in hypertension (OR:6.30, 95%CI: 3.49-11.36), proteinuria (OR:4.12, 95%CI: 1.25-13.61), epistaxis (OR:3.71, 95%CI: 2.84-4.85), III/IV hypertension (OR:7.20, 95%CI: 5.23-9.92), III/IV proteinuria (OR:5.13, 95%CI: 3.13-8.41). The funnel plot, Begg test and Egger test were carried out on the primary endpoints, III/IV hypertension rate and III/IV proteinuria rate, the result of which detected no obvious publication bias. No significant difference was observed in subgroup analysis in the primary endpoint between the subgroups stratified by treatment line (firstline or non-firstline), chemotherapy regime (FOLFIRI or others) and study design (RCTs or single-arm trials)., Conclusion: The available evidence suggests that using aflibercept is associated with an increased risk of antiangiogenic adverse events compared with controls. Further studies are needed to investigate this association. In the appropriate clinical scenario, the use of aflibercept in its approved indications remains justified. However, the results of this study should be interpreted with caution, as some of the evidence comes from single-arm clinical trials., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The early accurate diagnoses for autoimmune encephalitis (AE) and infectious encephalitis (IE) are essential since the treatments for them are different. This study aims to discover some specific and sensitive biomarkers to distinguish AE from IE at early stage to give specific treatments for good outcomes., Results: We compared the host gene expression profiles and microbial diversities of cerebrospinal fluid (CSF) from 41 patients with IE and 18 patients with AE through meta-transcriptomic sequencing. Significant differences were found in host gene expression profiles and microbial diversities in CSF between patients with AE and patients with IE. The most significantly upregulated genes in patients with IE were enriched in pathways related with immune response such as neutrophil degranulation, antigen processing and presentation and adaptive immune system. In contrast, those upregulated genes in patients with AE were mainly involved in sensory organ development such as olfactory transduction, as well as synaptic transmission and signaling. Based on the differentially expressed genes, a classifier consisting of 5 host genes showed outstanding performance with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.95., Conclusions: This study provides a promising classifier and is the first to investigate transcriptomic signatures for differentiating AE from IE by using meta-transcriptomic next-generation sequencing technology., (© 2023. The Author(s).)

Objective: To describe the clinical and neuroimaging characteristics of rheumatoid meningitis (RM) in Chinese patients., Methods: The patients admitted to our hospital with the diagnosis of RM in the past 8 years were retrospectively analyzed., Results: Six patients with RM were identified among 933 patients admitted with rheumatoid arthritis (RA). The symptoms of meningitis occurred after onset of arthritis in five patients and before onset in one. Headache (n=6), hyperacute focal neurological deficits (n=4) and seizures (n=3) were the most prevalent symptoms. The nadir modified Rankin Scale score was ≥3 in five patients. Rheumatoid factor was elevated in all patients, and interleukin-6 levels in cerebrospinal fluid were dramatically elevated in three of four tested patients. Magnetic resonance imaging of the brain revealed that the meninges were affected in all patients and the cerebral parenchyma was affected in one patient. The lesions were generally located in the frontoparietal region and showed restricted diffusion along the adjacent subarachnoid space. RM occurred during disease-modifying therapy in four patients. In the acute episode, three patients improved on tocilizumab and the other three improved on pulse corticosteroids. For maintenance therapy, two patients received combined therapy of tocilizumab and other immunosuppressive agents, one received adalimumab and methotrexate, and two received low-dose oral corticosteroids with an immunosuppressive agent. Five patients had a good outcome, and one died of Pneumocystis jirovecii pneumonia after stabilization of his neurologic conditions. No relapse of RM occurred on immunotherapy during follow-up., Conclusions: Chinese patients with RM share some remarkable clinical and neuroimaging features and respond well to appropriate immunotherapy. Tocilizumab could be a treatment option for this severe complication of RA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Fan, Zhao, Hou, Liu, Niu, Zhou, Mao, Ren, Feng, Li, Zeng, Zhu and Guan.)

Autoimmune cerebellar ataxia (ACA) is an important and potentially treatable cause of sporadic cerebellar syndrome, but studies with large sample size are limited. This study reported a large ACA series in China and described its etiology and clinical characteristics. We reviewed all ACA patients from our hospital (2013-2021) and analyzed their clinical and paraclinical features, treatment, and outcome. ACA subtypes investigated included paraneoplastic cerebellar degeneration (PCD), primary autoimmune cerebellar ataxia (PACA), anti-glutamate decarboxylase (GAD)-associated cerebellar ataxia, opsoclonus-myoclonus syndrome (OMS), Miller Fisher syndrome (MFS), and ACA-associated with autoimmune encephalitis. A total of 127 patients were identified and 40.9% were male. The median onset age was 47.0 years. Gait ataxia was the most prevalent feature followed by limb ataxia, dizziness, and dysarthria/dysphagia. Extracerebellar manifestations included pyramidal signs (28.3%) and peripheral neuropathy/radiculopathy (15.0%). ACA subtypes were PCD (30.7%), PACA (37.8%), ACA associated with autoimmune encephalitis (12.6%), anti-GAD-associated ACA (8.7%), MFS (7.1%), and OMS (3.1%). Neuronal antibodies were positive in 67.7% of patients. Brain magnetic resonance imaging was unremarkable (55.7%) or showed atrophy (18.3%) or abnormal signal intensity (26.1%, most of which was extracerebellar). Although most patients received immunotherapy, the modified Rankin scale at last follow-up was ≤ 2 in only 47.3% patients. Thirteen patients died and 24 relapsed. Compared with PACA, PCD patients were older and had poorer outcome. This study illustrates the heterogeneity in the clinical features of ACA and suggests the importance of neuronal antibody testing in ACA diagnosis. PCD and PACA are the dominant ACA subtypes, and the former has a less favorable prognosis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Encephalitis associated with antibodies against alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) is an extremely rare type of antibody-mediated encephalitis. This research aims to investigate the clinical characteristics and prognosis of anti-AMPAR encephalitis., Methods: This retrospective study enrolled nine patients with anti-AMPAR encephalitis. Demographic information, clinical manifestations, laboratory and radiological findings, treatment and response were collected and analyzed. These patients were followed up with an average period of 72 weeks to gather prognostic information., Results: Nine patients (7 females and 2 males) were enrolled with a mean age at disease onset of 59 years old. Three clinical pictures, including limbic encephalitis (n = 7; 78%), pure amnesia (n = 1; 11%) and fulminant encephalitis (n = 1; 11%) were identified. New symptoms of dysphagia and deafness were identified in the clinical spectrum of anti-AMPAR encephalitis. All patients had positive blood AMPAR antibodies, and six of them (67%) had paired positive antibodies in cerebrospinal fluid (CSF). Brain magnetic resonance imaging (MRI) was abnormal in 75% of the patients with no specific patterns recognized. Six patients (67%) had tumors, including lung cancers and thymomas. After immunotherapy and oncotherapy, partial improvement of neurological symptoms was observed among all 6 patients with available records during their hospitalization. After a mean follow-up of 72 weeks, 3 patients had marked decrease of modified Rankin Scale (mRS) score, 1 patient had unchanged mRS score, 4 patients died and the other one was lost., Conclusions: Anti-AMPAR encephalitis mainly presents as limbic encephalitis, and is paraneoplastic in 67% of cases. Thus, intensive screening for tumors is recommended for all anti-AMPAR patients. Although patients showed a good short-term therapeutic response, the overall prognosis was not satisfactory., (© 2021. The Author(s).)

Background and Objective: To present 6 new cases with Homer-3 antibodies that expand their clinical spectra and to evaluate the effect of immunotherapy., Methods: Patients with suspected autoimmune cerebellar disorder were tested for rare autoimmune cerebellar ataxia (ACA) antibodies (anti-Tr(DNER)/Zic4/ITPR1/Homer-3/NCDN/PKCγ/PCA-2/AP3B2/mGluR1/ATP1A3 antibodies) using both cell-based and tissue-based assays. Patients with positive serum or CSF results who were diagnosed with ACA were registered and followed up. This study reports and analyzes cases with Homer-3 antibodies., Results: Of the serum and CSF samples of 750 patients tested, 6 were positive for Homer-3 antibodies. All manifested subacute or insidious-onset cerebellar ataxia. Furthermore, 2 patients each exhibited encephalopathy, myeloradiculopathy, REM sleep behavior disorder, and autonomic dysfunction. Brain magnetic resonance images were normal (n = 1) or revealed cerebellar atrophy (n = 1), cerebellum and pons atrophy with the hot cross bun sign (n = 2), and bilateral cerebral abnormalities (n = 2). Definite leukocytosis was identified in the CSF of 2 patients, protein concentration elevation was observed in the CSF of 1 patient, and oligoclonal bands were present in 2 patients. All patients received immunotherapy, including corticosteroid, IV immunoglobulin, plasma exchange, and mycophenolate mofetil, after which the residual disability was still severe (modified Rankin Scale score ≥3 at the last follow-up in 4 patients and final Scale for the Assessment and Rating of Ataxia scores of 12-29), although 4 patients partially improved and 1 patient stabilized. The remaining 1 patient continued to deteriorate after repeated immunotherapy. Two patients relapsed., Discussion: Disorders associated with Homer-3 antibody can mimic multiple system atrophy with cerebellar features in both clinical and radiologic aspects. Accurate identification of autoimmune-mediated cases is critical. Timely, comprehensive immunotherapy is warranted, given the possibility of long-term clinical benefit., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Angiogenesis is essential for various physiological and pathological processes. Previous studies have shown that miRNAs play an important role in blood vessel development and angiogenesis. Recent studies have suggested that miR-181b might be involved in the regulation of angiogenesis in tumors. However, whether miR-181b plays a role in angiogenesis in nontumor diseases is unclear. We found that miR-181b expression was downregulated in hypoxia-stimulated primary human umbilical vein endothelial cells (HUVECs) and a mouse hindlimb ischemia (HLI) model. Gain- and loss-of-function studies showed that a miR-181b mimic inhibited HUVEC migration and tube formation in vitro, and a miR-181b inhibitor had the opposite effects. In vivo, agomir-181b suppressed perfusion recovery in the HLI model and capillary density in a Matrigel plug assay, while perfusion recovery and capillary density were increased by injection of antagomir-181b. Mechanistically, we showed with a reporter assay that cellular communication network factor 1 (CCN1) was a direct target of miR-181b. Moreover, miR-181b suppressed angiogenesis at least in part by targeting CCN1 to inhibit the AMPK signaling pathway. Our research suggests that miR-181b suppresses angiogenesis by directly targeting CCN1, which provides new clues for pro-angiogenic treatment strategies., (© 2021. The Author(s), under exclusive licence to United States and Canadian Academy of Pathology.)

Nonalcoholic fatty liver disease (NAFLD) is prevalent clinically and can lead to more serious chronic liver disease. However, the pathological mechanism is still unclear, and thus, there are no approved drugs on the market. Transcriptional coactivator WW domain-binding protein 2 (WBP2) is a newly discovered oncogene that has an important relationship with the occurrence and development of breast cancer and mediates the interaction between Wnt and various other signaling pathways. The expression level of WBP2 was decreased in NAFLD. Overexpression of WBP2 with AAV in vivo alleviated liver fat deposition and insulin resistance induced by a high-fat diet (HFD). Knockdown of WBP2 with AAV aggravated HFD-induced fatty liver and insulin resistance. In vitro experiments showed that in the human normal hepatocyte cell line LO2 and primary hepatocytes isolated from mice, overexpression of WBP2 reduced fat deposition, and knocking out or knocking down WBP2 aggravated PA-induced fat deposition. Through mass spectrometry, we found that WBP2 can bind to AMPKβ1, and by mutating AMPKβ1, we found that WBP2 can induce phosphorylation of AMPKβ1 at S108 and then activate the AMPK pathway to affect lipid metabolism. The effect of WBP2 on NAFLD provides a possible new direction for future research on NAFLD.

Anti-protein kinase Cgamma (anti-PKCγ) antibodies are rare onconeural antibodies associated with paraneoplastic cerebellar degeneration (PCD). To date, only two patients with PCD and anti-PKCγ antibodies have been reported. Here, we report a Chinese patient with PCD and anti-PKCγ antibodies. Screening for tumor revealed lymphoepithelial carcinoma in tonsil. The patient's symptoms improved gradually after radiotherapy for the lymphoepithelial carcinoma and intravenous immunoglobulin immunotherapy., Competing Interests: Declaration of Competing Interest All authors declare no competing interest., (Copyright © 2020. Published by Elsevier B.V.)

Pseudorabies virus (PRV) is known to cause severe encephalitis in juvenile pigs and various non-native hosts; recent evidences suggest that PRV might cause encephalitis in humans. In a multicenter cohort study in China, next-generation sequencing of cerebrospinal fluid (CSF) was performed to detect pathogens in all patients with clinically suspected central nervous system infections. This study involved all the patients whose CSF samples were positive for PRV-DNA; their clinical features were evaluated, and species-specific PCR and serological tests were sequentially applied for validation. Among the 472 patients tested from June 1, 2016, to December 1, 2018, six were positive for PRV-DNA, which were partially validated by PCR and serological tests. Additionally, we retrospectively examined another case with similar clinical and neuroimaging appearance and detected the presence of PRV-DNA. These patients had similar clinical manifestations, including a rapid progression of panencephalitis, and similar neuroimaging features of symmetric lesions in the basal ganglia and bilateral hemispheres. Six of the patients were engaged in occupations connected with swine production. PRV infection should be suspected in patients with rapidly progressive panencephalitis and characteristic neuroimaging features, especially with exposure to swine.

Background: To investigate the efficacy and safety of non-invasive brain stimulation for fatigue in multiple sclerosis patients., Methods: We searched MEDLINE, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, and Wanfang databases up to October 25, 2018 (PROSPERO registration number: CRD42018112823). Randomized or pseudo-randomized, sham-controlled clinical trials evaluating the effect of non-invasive brain stimulation (NIBS) such as transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (TMS), transcranial random noise stimulation (tRNS), transcranial alternating current stimulation (tACS), cranial electrotherapy stimulation, and reduced impedance non-invasive cortical electrostimulation were included. Two authors independently performed data extraction and risk of bias assessment according to Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1. The primary outcome was fatigue scores before and after stimulation and the secondary outcome was adverse events., Results: Data from cross-over and parallel group studies were pooled using a generic inverse-variance approach. A total of 14 studies (11 for tDCS, 2 for TMS, and 1 for tRNS) recruiting 207 patients were included in the systematic review and meta-analysis. No eligible tACS, cranial electrotherapy stimulation or reduced impedance non-invasive cortical electrostimulation studies were found. Short-term and long-term treatment effects were significant for tDCS, whereas TMS and tRNS were not superior to sham stimulation. The available evidence supported the effectiveness of the 1.5 mA subgroup and bilateral S1 subgroup of tDCS. Adverse events were minor and transient but comparable between real and sham stimulation., Conclusions: tDCS is a safe and effective treatment for fatigue in MS patients. However, further studies are required to confirm our results in a large-scale population and to investigate the effectiveness of other NIBS subtypes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To describe the detailed clinical characteristics, immunotherapy, and long-term outcomes of patients with anti-NMDA receptor (NMDAR) encephalitis in China., Methods: A single-center, prospective study. Patients who met the diagnostic criteria were enrolled from 2011 to 2017 and followed up. The clinical features, treatment, and long-term outcomes were collected prospectively. Factors affecting the long-term prognosis were analyzed., Results: The study included 220 patients. The most common clinical presentations were psychosis (82.7%) and seizures (80.9%). Of the patients, 19.5% had an underlying neoplasm; of which ovarian teratoma was 100% of tumors in females and only one male had lung cancer. Most patients (99.5%) received first-line therapy (glucocorticoids, IV immunoglobulin, or plasmapheresis alone or combined), and only 7.3% received second-line immunotherapy (rituximab, cyclophosphamide alone, or combined). Long-term immunotherapy (mycophenolate mofetil or azathioprine >1 year) was administered to 53.2% of patients. During the first 12 months, 207 (94.1%) patients experienced improvement, and 5 (2.3%) died, whereas 38 (17.3%) experienced relapses. At 12-month follow-up, 92.7% had favorable clinical outcomes (modified Rankin Scale score ≤2)., Conclusions: Patients in China present with psychosis and seizure frequently but have a low percentage of underlying neoplasms. Re-enforced first-line immunotherapy is effective in managing anti-NMDAR encephalitis in the acute phase. Although relapse is relatively common, with combined first-line and long-term immunotherapy, most patients reached favorable outcomes., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Gallium (Ga) is a critical element in developing renewable energy generation and energy efficient systems. The supply of Ga is at risk and needed recycling technologies for its availability in future. This study demonstrated the recovery of Ga 3+ from low gallium concentrated wafer fabrication industry wastewaters using the siderophores desferrioxamine B (DFOB) and desferrioxamine E (DFOE). The complexation of Ga 3+ by DFOB and DFOE was through hydroxamate group as demonstrated by infrared spectroscopy, nuclear magnetic resonance and density functional theory calculations. The high selectivity of DFOB/E towards Ga 3+ was observed due to the formation of highly stable complex. Indeed, due to the formation of such high stability complex, the DFOB and DFOE were able to successfully complex 100% Ga in the two different process water from wafer fabrication industry. For the recovery of the siderophores, a high rate of decomplexation of Ga (>90%) was achieved upon addition of 6 times excess of ethylenediaminetetraacetic acid (EDTA) at pH of 3.5. More than 95% of Ga-DFOB and Ga-DFOE complex were recovered with purity (% of Ga moles in comparison to total moles of metals) of 69.8 and 92.9%, respectively by application of a C18 reversed-phase chromatography column. This study, for the first time, demonstrated a technical solution to the recovery of Ga 3+ from the low concentrated wastewater based on siderophores and reversed-phase chromatography. A German patent application had been filed for this technology., (Copyright © 2019. Published by Elsevier Ltd.)

Anticoagulant therapy is an effective stroke prevention measurement for subjects with atrial fibrillation (AF) who are at high risk of ischemic stroke. However, it is reported that oral anticoagulants (OACs) are generally underused in clinical practice. A better awareness of current usage of anticoagulant therapy would enable prevention of stroke secondary to AF. Therefore, we determined the nationwide prevalence of AF and the frequency of OACs use among patients with ischemic stroke in China. Based on the China National Stroke Screening Survey, a representative nationwide sample of 1,252,703 adults over 40 years old during 2013 and 2014 was involved. Information on demographic data, diagnosis of stroke, behavioral risk factors, family history of stroke, related diseases, and medications was collected. The community-based survey data showed that 5,588 patients (12.0%) with ischemic stroke had previous, or newly diagnosed, AF. Therefore, more than 2.15 million ischemic stroke patients had AF in China. Among ischemic stroke patients with AF, the strongest risk factor was coronary heart disease (odds ratio = 2.53), whereas dyslipidemia accounted for the largest contribution (population-attributable risk proportion = 17.33%). Of ischemic stroke patients with AF, only 2.2% had taken OACs; of them, 98.2% had taken warfarin. In conclusion, a large number of ischemic stroke patients with AF are significantly undertreated with OACs in China. This highlights the need for improvement of prevention of ischemic stroke secondary to AF., (Copyright © 2018. Published by Elsevier Inc.)

Background: Brucellosis is the most common zoonotic infection in the world. Brucellosis with nervous system involvement is known as 'neurobrucellosis' (NB). The diagnosis of NB is difficult because its clinical manifestations are non-specific and the sensitivity of routine culture tests is low., Methods: Next-generation sequencing (NGS) of cerebrospinal fluid (CSF) was used to detect pathogens in patients with clinically suspected central nervous system (CNS) infections at a tertiary referral center in China between June 1, 2016 and June 1, 2017. The clinical characteristics and NGS results of patients with the diagnosis of NB were reviewed in this study., Results: Four patients were rapidly diagnosed with NB using NGS of the CSF in patients with clinically suspected CNS infections, although the clinical manifestations varied dramatically between these patients. NGS of the CSF revealed that the sequence reads identified that corresponded to Brucella species ranged from 11 to 104, with genomic coverage ranging from 0.043% to 0.4%. Rapid diagnosis led to prompt treatment with the appropriate antibiotics., Conclusions: This study demonstrates the power of NGS of the CSF coupled with a bioinformatic pipeline in the diagnosis of NB., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Myelin oligodendrocyte glycoprotein (MOG)-antibody (ab) disease and AQP4-IgG-positive neuromyelitis optica spectrum disorder (NMOSD) can co-exist with anti-NMDA (N-methyl-D-aspartate) receptor encephalitis (NMDARe)., Objectives: To characterize MOG-ab disease and AQP4-IgG-positive NMOSD during NMDARe., Methods: We analyzed all the patients with overlapping MOG-ab disease and NMDARe (MNOS) and patients with AQP4-IgG-positive NMOSD and NMDARe (ANOS) in our hospital and compared those data with data from systematically review of previously published reports., Results: In our cohorts, 11.9% patients with MOG-ab disease and 0.6% patients with NMOSD had overlapping NMDARe (P < 0.01). After treatment with steroids and/or intravenous immunoglobulin (IVIg), the median modified Rankin Scale (mRS) of the MNOS group decreased significantly during attacks associated with or without NMDARe (P < 0.01 for both), while that of the ANOS group did not (attack: P < 0.05; attack associated with NMDARe: P > 0.05). Analyzed together with previously reported cases, 6% patients with MNOS and 40% patients with ANOS also used rituximab or cyclophosphamide after steroids and/or IVIg (P < 0.05) during attacks associated with NMDARe., Conclusion: Compared with NMOSD, MOG-ab disease may more commonly co-exist with NMDARe. MNOS patients respond better to steroids and IVIg than do ANOS patients during attacks associated with NMDARe., (Copyright © 2018 Elsevier B.V. All rights reserved.)