Lactobacillus Reuteri Vesicles Regulate Mitochondrial Function of Macrophages to Promote Mucosal and Cutaneous Wound Healing.

The interplay between bacteria and their host influences the homeostasis of the human immune microenvironment, and this reciprocal interaction also affects the process of tissue damage repair. A variety of immunomodulatory commensal bacteria reside in the body, capable of delivering membrane vesicles (MVs) to host cells to regulate the local immune microenvironment. This research revealed, for the initial time, the significant enhancement of mucosal and cutaneous wound healing by MVs secreted by the human commensal Lactobacillus reuteri (RMVs) through modulation of the inflammatory environment in wound tissue. Local administration of RMVs reduces the proportion of pro-inflammatory macrophages in inflamed tissues and mitigates the level of local inflammation, thereby facilitating the healing of oral mucosa and cutaneous wounds. The elevated oxidative stress levels in activated pro-inflammatory macrophages can be modulated by RMVs, resulting in phenotypic transformation of macrophages. Furthermore, 3-hydroxypropionaldehyde present in RMVs can decrease the mitochondrial permeability of macrophages and stabilize the mitochondrial membrane potential, thereby promoting the conversion of macrophages to an anti-inflammatory phenotype. This study pioneers the significance of commensal bacterial MVs in tissue injury repair and presents a novel concept for the repair of tissue damage.

Research on factors influencing Chinese parents' support for death education: a cross-sectional survey.

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 (ß = 0.04, p < 0.001), education level (ß = 0.07, p < 0.001), and religious belief (ß = -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 (ß = 0.07, p < 0.001), family health (ß = 0.03, p < 0.05), family communication (ß = 0.02, p < 0.05), social support (ß = 0.15, p < 0.001), neighborhood relations (ß = 0.11, p < 0.001), and social network size (ß = 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.

TRAF2 decrease promotes the TGF-ß-mTORC1 signal in MAFLD-HCC through enhancing AXIN1-mediated Smad7 degradation.

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-ß (TGF-ß). The decisive role of TGF-ß in the development of MAFLD-HCC was confirmed through the specific depletion of TGF-ß receptor II gene in the hepatocytes (Tgfbr2ΔHep) of mice. In TRAF2-/- cells treated with TGF-ß, 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-ß, 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-ß 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-ß-mTORC1 pathway by facilitating AXIN1-mediated Smad7 degradation.

Febrile infection-related epilepsy syndrome with claustrum lesion: an underdiagnosed inflammatory encephalopathy.

OBJECTIVE: To summarize the clinical characteristics and prognosis of febrile infection-related epilepsy syndrome with claustrum lesions (FIRES-C). METHOD: Clinical data of FIRES-C patients were collected retrospectively. The study reviewed and analyzed their clinical manifestations, treatment strategies, and prognosis. RESULT: Twenty patients were enrolled, including 13 females and 7 males, with a median onset age of 20.5 years. All patients developed seizures after fever, with a median interval of 5 days. Brain MRI showed symmetric lesions in the claustrum in all patients. The median interval from seizure onset to abnormal MRI signals detection was 12.5 days. All patients had negative results for comprehensive tests of neurotropic viruses and antineuronal autoantibodies. Seventy percent of cases had been previously empirically diagnosed with autoimmune encephalitis or viral encephalitis before. All patients received anti-seizure medicine. Eleven patients (55%) received antiviral therapy. All patients received immunotherapy, including glucocorticoids (100%), intravenous immunoglobulin (IVIg) (65%), plasma exchange (PLEX) (10%), tocilizumab (10%), rituximab (5%), and cyclophosphamide (5%). Sixty percent of patients received long-term immunotherapy (≥ 3 months). The median follow-up was 11.5 months;60% of patients were diagnosed with refractory epilepsy. CONCLUSION: Bilateral claustrum lesion on MRI is a distinctive neuroimage feature for FIRES, which may serve as an indication for the initial clinical assessments. FIRES-C should be classified as a type of inflammatory encephalopathy characterized by a monophasic nature. Some FIRES-C patients respond to immunotherapy and antiseizure treatments but most experience refractory epilepsy as a long-term outcome.

Mycophenolate mofetil reduces the risk of relapse in anti-leucine-rich glioma-inactivated protein 1 encephalitis: a prospective observational cohort study.

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.

Prognostic and relapsing factors of primary autoimmune cerebellar ataxia: a prospective cohort study.

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.

Experimental investigation and theoretical analysis of the breakdown time delay and jitter of multi-gap gas switch gaps.

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.

CD9 exacerbates pathological cardiac hypertrophy through regulating GP130/STAT3 signaling pathway.

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.

Pembrolizumab for the treatment of progressive multifocal leukoencephalopathy in China.

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.

Diagnostic Superiority of 18 F-FDG PET Over MRI in Detecting Anti-LGI1 Autoimmune Encephalitis : A Comparative Study With Insights Into Faciobrachial Dystonic Seizures Mechanisms and Recurrence Identification.

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.

Risk of antiangiogenic adverse events in metastatic colorectal cancer patients receiving aflibercept in combination with chemotherapy: A meta-analysis.

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.

Integrating host transcriptomic signatures for distinguishing autoimmune encephalitis in cerebrospinal fluid by metagenomic sequencing.

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.

Rheumatoid meningitis: a rare neurological complication of rheumatoid arthritis.

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.

Anti-metabotropic glutamate receptor 5 encephalitis: Five case reports and literature review.

OBJECTIVE: To describe the clinical and radiological characteristics of anti-metabotropic glutamate receptor 5 (mGluR5) encephalitis. METHODS: We reviewed the clinical data of five patients with anti-mGluR5 encephalitis, and performed a literature review. RESULTS: The five cases included a 52-year-old man who developed a biphasic course of anti-mGluR5 encephalitis after herpes simplex encephalitis, a 22-year-old woman who showed bilateral basal ganglia lesions on brain magnetic resonance imaging (MRI), and a 36-year-old man with mixed aphasia and generalized tonic-clonic seizures, a 51-year-old man presented with personality changes, hallucinations, delusions, sleeping disorders and a 58-year-old man with short-term memory deficits and absence seizures.. There are 16 reported cases of anti-mGluR5 encephalitis worldwide. Of all 21 patients, with a median onset age of 35 years old, the main neurological symptoms were cognitive impairment (85.7%, 18/21), psychiatric or behavior problems (76.2%, 16/21), seizures (57.1%, 12/21), sleeping disorders (52.4%, 11/21), different degrees of decreased consciousness (42.9%, 9/21), and movement disorders (23.8%, 5/21). Brain MRI was normal in 11 of 21 patients. Lesions of the limbic lobes were presented in 5 patients, while involvement of other extralimbic regions was also reported. Seven of 21 (33.3%) cases were combined with tumors. Elevated white blood cell counts or specific oligoclonal IgG bands in the cerebrospinal fluid were found in 18 of 21 patients, with marked improvements observed after immunotherapy. DISCUSSION: Patients with anti-mGluR5 encephalitis typically present with diffuse, rather than purely limbic, encephalitis. Anti-mGluR5 encephalitis can be triggered by herpes simplex encephalitis. The risk of a combined tumor may be reduced in anti-mGluR5 encephalitis patients.

Reliability and validity of the Chinese version of the Sakata Eating Behavior Scale short form and preliminary analysis of the factors related to the score of the scale.

Background: The obesity rate in the Chinese population is increasing and there is a lack of short and reliable scales for measuring obesity-related eating behavior in China. The EBS-SF (Sakata Eating Behavior Scale short form) has only 7 entries and has shown good reliability in studies such as those in Japan. Objective: To translate the EBS-SF into Chinese, check its reliability, validity and explore the related factors. Method: The EBS-SF was translated into Chinese. 3,440 residents were investigated and 34 respondents were retested. Item analysis and reliability and validity tests were carried out. Personality characteristics, family health status and depression were investigated using the BFI-10, FHS-SF and PHQ-9 to investigate the factors associated with EBS-SF. The t-test, ANOVA and Pearson correlation was used to explore the related factors of its scores. Result: Among 3,440 residents, 1,748 (50.81%) were male and 1,692 (49.19%) were female; 1,373 (39.91%) were aged 36-50 years. All 7 items were qualified in the item analysis. As for reliability, the Cronbach's α was 0.870, the split-half reliability was 0.830, the test-retest correlation coefficient was 0.868. As for the structural validity, the standardized factor loadings were above 0.50, χ2 / df = 2.081,GFI = 0.999; NFI = 0.999; RFI = 0.996; RMSEA = 0.018, all qualified. The characteristics, personality, family health and depression were correlated with the score of the Chinese version of EBS short form. Conclusion: The structural validity and reliability of the Chinese version of the EBS-SF are good and it can be used as a measurement tool to evaluate the eating behavior of Chinese. The scores of the EBS-SF may be related to the sociological characteristics, personality, family health, and depression status.

Autoimmune Cerebellar Ataxia: Etiology and Clinical Characteristics of a Case Series from China.

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.

Autoantibodies against eukaryotic translation elongation factor 1 delta in two patients with autoimmune cerebellar ataxia.

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.

Neurological disorders associated with glutamic acid decarboxylase 65 antibodies: Clinical spectrum and prognosis of a cohort from China.

Objective: To describe clinical phenotypes and prognosis of neurological autoimmunity related to glutamic acid decarboxylase 65 (GAD65) antibodies in China. Method: In this retrospective observational study from Peking Union Medical College Hospital, we identified patients with neurological disorders related to GAD65 antibodies (cell-based assay) from May 2015 to September 2021. Clinical manifestations, immunotherapy responsiveness, and outcomes were collected after obtaining informed consent from all patients. Results: Fifty-five patients were included: 40 (72.73%) were women and initial neurological symptoms developed at 42(34-55) years of age. The median time to the nadir of the disease was 5 months (range from 1 day to 48 months). The clinical syndromes included limbic encephalitis (LE) or epilepsy (Ep) (n = 34, 61.82%), stiff-person syndromes (SPS) (n = 18, 32.73%), autoimmune cerebellar ataxia (ACA) (n = 11, 20%), and overlap syndrome in eight (14.55%) patients. Thirty-two (58.2%) patients had comorbidities of other autoimmune diseases, including Hashimoto thyroiditis (n = 17, 53.13%), T1DM (n = 11, 34.78%), vitiligo (n = 6, 18.75%), and others (n=5, 15.63%). Two (3.64%) patients had tumors, including thymoma and small cell lung cancer. Fifty-one (92.7%) patients received first-line immunotherapy (glucocorticoids and/or IV immunoglobulin), and 4 (7.3%) received second-line immunotherapy (rituximab). Long-term immunotherapy (mycophenolate mofetil) was administered to 23 (41.8%) patients. At the median time of 15 months (IQR 6-33.75 month, range 3-96 month) of follow-up, the patients' median modified Rankin Score (mRS) had declined from 2 to 1. Thirty-eight (70.4%) patients experienced clinical improvement (mRS declined ≥1), 47 (87%) had favorable clinical outcomes (mRS ≤2), and nine were symptom-free (16.7%). The sustained response to immunotherapy ranged from 7/15 (63.63%) in ACA patients and 22/34 (64.7%) in LE/Ep patients to 14/17 (82.35%) in SPS patients. Conclusions: LE/Ep was the most common neurological phenotype of GAD65 antibody neurological autoimmunity in our cohort. Most patients had comorbidities of other autoimmune diseases, but underlying tumors were rare. Most patients responded to immunotherapy. However, the long-term prognosis varied among different clinical phenotypes.

The "hot cross bun sign" in patients with autoimmune cerebellar ataxia: A case report and literature review.

Objectives: The "hot cross bun sign" (HCBs) on magnetic resonance imaging (MRI) has been initially considered specific for multiple system atrophy with cerebellar features. However, a number of other conditions have since been described, which may be associated with this imaging sign. We herein describe a patient with anti-Ri and paraneoplastic cerebellar ataxia, and review the association of the HCBs on imaging with various neurological autoimmune conditions. Methods: We report a 40-year-old woman with anti-Ri-associated paraneoplastic neurological syndrome and breast carcinoma, in whom brain MRI revealed the HCBs late in the disease course. We also reviewed similar cases reported in the literature. Results: The patient presented with cerebellar ataxia, polyneuropathy, and pyramidal signs. Although brain MRI was initially unremarkable, the HCBs and T2-weighted hyperintensity of the bilateral middle cerebellar peduncles were observed at later follow-up. Anti-Ri was detected in the serum and cerebrospinal fluid. Breast adenocarcinoma was confirmed via an axillary lymph node biopsy. Her symptoms partially resolved after the first corticosteroid pulse. However, subsequent immunotherapy and tumor treatments were ineffective. Four autoimmune cerebellar ataxia cases with the HCBs (two paraneoplastic and two non-paraneoplastic) were identified in the literature. Discussion: The HCBs can be associated with paraneoplastic and non-paraneoplastic cerebellar ataxia, which may reflect neurodegeneration secondary to autoimmune injury. Thus, the HCBs should not be considered a contraindication for autoimmune cerebellar syndrome.

Media use degree and depression: A latent profile analysis from Chinese residents.

Background: Previous studies have emphasized the media as an essential channel for understanding information about depression. However, they have not divided groups according to the degree of media use to study their differences in depression. Therefore, this study aims to explore the influence of media use on depression and the influencing factors of depression in people with different media use degrees. Methods: Based on seven items related to media use, a total of 11, 031 respondents were categorized by the frequency of media use using latent profile analysis (LPA). Secondly, multiple linear regression analyzes were conducted to analyze the effects of depression in people with different degrees of media use. Finally, factors influencing depression among people with different degrees of media use were explored separately. Results: All respondents were classified into three groups: media use low-frequency (9.7%), media use general (67.1%), and media use high-frequency (23.2%). Compared with media use general group, media use low-frequency (ß = 0.019, p = 0.044) and media use high-frequency (ß = 0.238, p < 0.001) groups are significantly associated with depression. The factors influencing depression in the population differed between media use low-frequency, media use general, and media use high-frequency groups. Conclusion: The government and the appropriate departments should develop targeted strategies for improving the overall health status of people with different media use degrees.