Background: Huafeng Dan (HFD) is a traditional famous medicine from Guizhou Province, commonly used for the treatment of stroke-induced hemiplegia and epilepsy. Yaomu is a key component and serves as the sovereign herb in the formula. Most of the components of Yaomu are toxic Chinese herbal medicines. Traditional fermentation processing methods are required to reduce its toxicity. Purpose: Current studies have not yet systematically analyzed the chemical constituents before and after fermentation. Meanwhile, there is a lack of safety evaluation before and after the fermentation of Yaomu, which can provide a basis for safe clinical medication. Method: Chemical constituents of Yaomu before and after processing were analyzed using UHPLC-Q/TOF-MS to compare compositional changes induced by fermentation. To further screen potential toxic components, representative compounds were selected from these differential compounds based on statistical indicators (such as VIP value), low cost and easy availability, as well as criteria from the literature, and the content changes before and after fermentation were investigated. In vitro toxicity was evaluated using a microfluidic liver organ-on-a-chip model to assess the toxic effects of Yaomu extracts before and after fermentation. Results: Studies have shown that in both positive and negative ionization modes, a total of 361 compounds were annotated in unfermented Yaomu. After fermentation, a total of 350 compounds were annotated. Multivariate statistical analysis revealed significant differences in the chemical composition of Yaomu before and after fermentation. Quantitative analysis demonstrated that the levels of diester-type diterpenoid alkaloids were significantly reduced after fermentation, accompanied by concurrent decreases in lysophosphatidylcholine (LPC) species, compared with unfermented Yaomu. In contrast, the concentrations of amino alcohol-type diterpenoid alkaloids were significantly increased. The microfluidic liver organ-on-a-chip results demonstrated that the post-fermentation extract caused significantly attenuated impairment of hepatocellular function and viability. The in vitro toxicity findings showed good concordance.

Background:Central nervous system (CNS) invasive fungal infections caused by Aspergillus spp. and Mucorales are associated with high mortality and severe neurological disability, but predictors of functional outcome remain poorly defined. We compared clinical features, neuroimaging patterns, and outcomes among rhino-orbital-cerebral mucormycosis (ROCM), rhino-cerebral aspergillosis (RA), and cerebral aspergillosis (CA), and identified prognostic factors for mortality and functional outcome. Methods:We performed a retrospective cohort study of 57 adults with proven or probable invasive CNS fungal infection (28 ROCM, 13 RA, 16 CA) treated between January 2018 and April 2025. An exploratory imaging-based angioinvasion severity score (0-3) was constructed from three radiographic markers: internal carotid artery involvement, cerebral infarction, and intracranial hemorrhage. The primary outcome was all-cause mortality during follow-up; 90-day mortality was also assessed. The secondary outcome was 90-day unfavorable functional outcome, defined as modified Rankin Scale (mRS) 3-6. Multivariable analyses used Cox regression, Firth penalized logistic regression, and proportional odds ordinal logistic regression. Results:ROCM had the highest 90-day mortality (43% vs. 7.7% in RA and 6.3% in CA; p = 0.009) and the lowest rate of favorable 90-day functional outcome (50% vs. 92% and 81%; p = 0.012). Moderate-to-severe angioinvasion (score ≥2) was associated with worse 90-day ordinal disability (common OR 8.61, 95% CI 1.87-39.58; p = 0.006). Lower admission Glasgow Coma Scale (GCS) score independently predicted mortality (adjusted HR 0.77, 95% CI 0.67-0.88; p < 0.001) and unfavorable functional outcome (adjusted OR 0.68, 95% CI 0.36-0.91; p = 0.006). After adjustment for angioinvasion burden and GCS, fungal phenotype was not independently associated with prognosis. The prediction model for unfavorable functional outcome showed good discrimination (AUC 0.888). Conclusions:Higher angioinvasion severity was associated with worse neurological functional outcome, whereas admission GCS independently predicted both mortality and unfavorable functional outcome. These findings may assist early risk stratification and treatment planning in invasive CNS fungal infection.

Daphnoretin (DAP) has various pharmacological activities, but its in vivo disposition after nanomicellar formulation remains unclear. This study compared the pharmacokinetics and tissue distribution of free DAP and two polymeric nanomicellar formulations, PP-DAP and GA-DAP, following intravenous administration. Plasma DAP concentrations in rats were determined by UPLC-MS/MS, and DAP concentrations in mouse tissues were determined by LC-MS/MS. Compared with free DAP, PP-DAP and GA-DAP showed higher systemic exposure, longer apparent elimination half-lives, and lower apparent clearance. The AUC0-∞ values of DAP, PP-DAP, and GA-DAP were 5474.14, 11,211.04, and 15,019.86 h · ng/mL, respectively, and the corresponding T1/2 values were 6.84, 9.24, and 9.90 h. DAP was detected in the heart, liver, spleen, lung, and kidney, with the nanomicellar formulations showing altered tissue distribution and GA-DAP exhibiting relatively sustained hepatic distribution. These findings suggest that nanomicellar formulation alters the in vivo disposition of DAP. However, free and micelle-associated DAP were not separately quantified, precluding direct characterization of in vivo drug release, and the validation range of the tissue quantification method was limited. Further studies are warranted to evaluate the in vivo behavior and liver-directed delivery potential of GA-DAP.

Fermentation is a significant and specialized processing technology that primarily serves to enhance efficacy and reduce toxicity. Yaomu (YM) was fermented in a cellar using bovine bile as the fermentation matrix. However, the alterations in its active ingredients before and after processing remain poorly understood. An aggregation-induced emission fluorescence sensor (NITPA-S) was developed that employed S-2238 (S) to encapsulate the NITPA-Py-603 (NITPA) probe with the help of glutaraldehyde, creating an "ON" state. Thrombin hydrolyzed the sensor, releasing the probe in the "OFF" state, while thrombin inhibitors reversed this effect. We combined an HPLC fully automatic partial fraction collector and UHPLC-Q-TOF/MS for the separation, screening and identification of YM active compounds, which were used as indicators of anticoagulant activity to explore the changes in the content of YM before and after processing by using UHPLC-MS/MS and the sensor. A total of 211 compounds were collected and identified. Notably, karakoline, talatisamine, neoline, chasmanine and schaftoside exhibited the highest inhibition rates in YM. Furthermore, these compounds generally increased in concentration after processing (p < 0.05). The anticoagulant inhibition rates of the mixture of these five compounds were 86.48% and 83.44% when compared with those of unfermented YM and YM, respectively. Consequently, the fluorescent sensor could completely screen out the anticoagulant active ingredients, providing a novel analytical approach for exploring and screening changes in the active components before and after TCM processing.

Diffuse midline glioma H3 K27-altered is a subtype of pediatric-type diffuse high-grade gliomas, characterized as an infiltrative high-grade glioma involving midline structures with H3 K27 mutation. This clinically rare entity poses diagnostic challenges in the early stages and carries an extremely poor prognosis. We report a case of diffuse midline glioma H3 K27-altered, primarily manifesting as spinal cord lesions, and detail its clinical characteristics to enhance understanding of this disease entity. A 21-year-old male presented with "progressive quadriparesis over 7 months." Seven months prior, he had developed bilateral lower limb weakness (grade II) following a cold. MRI at a local hospital revealed abnormal signals at T2-T5, diagnosed as "myelitis." The disease progressed with lesion expansion despite treatment with glucocorticoid pulse therapy and intravenous immunoglobulin. The patient visited our hospital 7 months after the onset of the disease. At that time, the patient exhibited grade I muscle strength in the right upper limb and grade 0 in all other limbs, with sensory impairment below the neck. MRI revealed abnormal signals in the medulla oblongata and thoracic spinal cord. The patient received high-dose glucocorticoid pulse therapy again, but the symptoms did not improve despite treatment. The definitive diagnosis of diffuse midline glioma H3 K27-altered was established through spinal cord biopsy. The patient was discharged from the hospital due to respiratory failure 12 days post-diagnosis.

Cerebral ischemia-reperfusion injury (CIRI) is classified under the category of stroke. Sanhua Decoction (SHD) is a classic prescription for the treatment of stroke, but its pharmacodynamic material basis and mechanism of action have not been fully elucidated. This study aimed to elucidate the bioactive components and therapeutic mechanisms of SHD against CIRI by integrating serum pharmacochemistry, network pharmacology, and metabolomics. Using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry, a 22 absorbed SHD prototype compounds were identified from rat serum. Through the application of network pharmacology and molecular docking technology, it was concluded that the key active ingredients, such as marmesin and aloe-emodin, mainly play a therapeutic role through key targets such as steroid receptor coactivator (SRC) and protein kinase B1 (AKT1). Molecular docking showed that these targets had strong affinity with key compounds. The results of pharmacodynamics showed that SHD could improve the neurological function score of CIRI rats, reduce the infarct area, and improve the pathological changes of brain tissue. Metabolomics analysis showed that SHD may play a therapeutic role by regulating steroid hormone synthesis and ubiquinone-related pathways. This study provides a methodological framework for exploring the role of Chinese herbal compounds in the treatment of CIRI.

Guillain–Barré syndrome (GBS) is an acute immune-mediated peripheral neuropathy typically characterized by a monophasic course; however, atypical or relapsing presentations suggest that sustained immune dysregulation contribute to disease heterogeneity. We report a 33-year-old man with progressive limb weakness diagnosed as motor-predominant acute inflammatory demyelinating polyradiculoneuropathy (AIDP), supported by albuminocytologic dissociation and demyelinating features on nerve conduction studies with preserved sensory conduction. Immunological evaluation revealed B lymphocyte expansion, elevated interleukin-6 and interleukin-8 levels, and strong thyroid autoantibody positivity consistent with Graves’ disease, while anti-ganglioside and paraneoplastic antibodies were negative. The clinical course was marked by immune-triggered relapses and the patient responded well to intravenous immunoglobulin (IVIg) and FcRn inhibition with efgartigimod. Further investigation identified papillary thyroid carcinoma harboring a BRAF V600E mutation, after which neurological symptoms stabilized following thyroidectomy. This case illustrates a rare concurrence of relapsing AIDP, Graves’ disease, and papillary thyroid carcinoma, and supports the hypothesis that persistent systemic immune activation underlies relapsing GBS, rather than a chronic demyelinating process. Clinically, it highlights the importance of considering underlying autoimmune and neoplastic conditions in atypical or relapsing GBS to guide individualized management.

Ethnopharmacological relevance Huafengdan (HFD), a traditional Chinese medicine from Guizhou, is known for its efficacy in treating ischemic stroke (IS). Yaomu, a principal component of HFD, undergoes fermentation, yet the role of this process in enhancing HFD’s therapeutic effects remains unclear. Investigating the synergistic mechanism of fermented Yaomu in HFD’s treatment of IS provides a theoretical basis for its clinical application. Purpose This study aimed to explore how Yaomu fermentation enhances HFD’s effectiveness and elucidates the underlying mechanisms. Methods Differential components of HFD, with and without fermented Yaomu, were identified using UPLC-Q-TOF-MS/MS. Newly added and upregulated components underwent network pharmacological analysis. An IS rat model was established, and neurobehavioral scores, cerebral infarction volumes, and levels of superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured to assess efficacy. Multivariate statistics and pathway analyses were conducted using UPLC-Q-TOF-MS/MS data. A “metabolite-enzyme-reaction-gene” network, integrating pharmacological and metabolomic data, identified key synergistic pathways, which were validated through protein analysis. Results The UPLC-Q-TOF-MS/MS analysis identified 54 novel components in HFD after Yaomu fermentation and detected 51 differential components between fermented and unfermented HFD, with 15 components downregulated and 36 upregulated. Network pharmacology revealed 53 active synergistic components and 642 component-disease intersection targets. Enrichment analysis of these intersecting targets indicated that Yaomu fermentation might enhance HFD’s efficacy by influencing the cAMP signaling pathway and neuroactive ligand-receptor interactions. Pharmacodynamic studies demonstrated that both HFD and HFD containing unfermented Yaomu significantly reduced neurobehavioral scores and infarct volumes in IS models, elevated SOD levels, and decreased MDA, TNF-α, and IL-6 levels. However, the efficacy of HFD was significantly higher than that of HFD containing unfermented Yaomu. Metabolic analysis identified five critical pathways involved in HFD’s therapeutic effects on IS, while three pathways were associated with the synergistic impact of Yaomu fermentation on HFD. By integrating network pharmacology and metabolomics, the “metabolite-enzyme-reaction-gene” network was constructed, revealing tryptophan metabolism as the primary synergistic pathway. Conclusion Yaomu fermentation enhances the therapeutic efficacy of HFD in IS treatment, primarily through the tryptophan metabolism pathway.

Building upon the spectrum-effect relationship theory in traditional Chinese medicine, ultraperformance liquid chromatography (UPLC) was utilized to generate fingerprint profiles for 12 batches of Sanhua Decoction (SHD). These profiles were analyzed in relation to pharmacological efficacy, providing a novel strategy to elucidate the material basis of SHD against cerebral ischemia-reperfusion injury (CIRI) and for efficacy evaluation. The UPLC fingerprints identified 33 common peaks, with 28 chemical constituents characterized. Pharmacodynamic assessment using a rat CIRI model demonstrated that SHD significantly improved neurological deficit scores, reduced cerebral infarct volume, and enhanced brain histopathology, with effects correlated to key indicators such as vascular endothelial growth factor. Gray relational analysis showed that 32 of the 33 peaks had a correlation degree greater than 0.706 with efficacy, confirming the synergistic effect of multiple components in SHD's anti-CIRI action. Orthogonal partial least-squares discriminant analysis identified 11 potential major active compounds significantly associated with anti-CIRI activity. An "efficacy-integrated fingerprint" was constructed by integrating chemical fingerprinting with pharmacodynamic indices, reflecting the intrinsic quality of SHD. This methodology offers a scientific and efficient approach for chemical constituent investigation and pharmacodynamic material basis elucidation of SHD and other traditional Chinese medicines.

We aimed to evaluate the association between rituximab (RTX) treatment duration and relapse risk, and explore clinical outcomes following treatment discontinuation in neuromyelitis optica spectrum disorder (NMOSD). We retrospectively collected data from rituximab-treated patients (>1-year follow-up after treatment initiation) with NMOSD at five major clinical centers in China between 2016 and 2023. The main outcome measures were changes in relapse risk based on the RTX treatment duration and clinical outcomes following relapse after RTX discontinuation. The Andersen–Gill model was used to analyze treatment duration-relapse risk associations. In total, 106 rituximab-treated patients were included (40 patients discontinued and 66 continued RTX). Longer RTX treatment significantly reduced relapse risk (hazard ratio [HR]=0.43, P < 0.001). Among 28 patients who discontinued RTX and were followed-up for >1 year after drug withdrawal, 53.6

BACKGROUND AND OBJECTIVES:To compare the efficacy and safety of telitacicept versus mycophenolate mofetil (MMF) in reducing relapses and disability in adults with neuromyelitis optica spectrum disorder (NMOSD). METHODS:In this retrospective cohort study, we analyzed 41 adults with NMOSD (2015 diagnostic criteria). Patients received ≥6 months of telitacicept or MMF treatment. Primary outcomes were annualized relapse rate (ARR) and relapse-free survival; secondary outcomes included Expanded Disability Status Scale (EDSS) score, CD19 + B-cell count, and safety. RESULTS:Over a median follow-up of 8 months for telitacicept (n = 15) and 9 months for MMF (n = 26), patients receiving telitacicept exhibited an 86.7% relapse-free rate (13/15) versus 57.6% (15/26) with MMF, with a significantly prolonged time to first relapse (hazard ratio 0.22, 95% confidence interval: 0.05-0.91; P = 0.04). The magnitude of ARR reduction was significantly greater with telitacicept (median ΔARR 2.0 [interquartile range (IQR) 2.0-4.0]) than with MMF (2.0 [1.0-2.0]; P = 0.007). Neurological function improved markedly, evidenced by a 2.5-point reduction (IQR: 2.0-3.0) in EDSS scores with telitacicept versus 0.5 points (IQR: 0.5-1.0) for MMF ( P < 0.001). Mechanistically, telitacicept induced deeper CD19 + B-cell suppression (Δ51.0 cells/μL [42.0-70.0]) than MMF (Δ28.5 cells/μL [8.0-40.2]; P = 0.002). Safety profiles favored telitacicept, with adverse events occurring in 20.0% (3/15) versus 42.3% (11/26) in the MMF group, though no severe events were observed in either cohort. CONCLUSION:Both telitacicept and MMF demonstrated favorable clinical efficacy and safety in NMOSD treatment. Compared with MMF, telitacicept exhibits potential advantages and holds promising prospects for clinical application.

Objective:To investigate the clinical features, neuroimaging characteristics, and prognosis of patients with anti-leucine-rich glioma-inactivated 1 (LGI1) antibody associated encephalitis. Methods:We conducted a retrospective study of 87 patients diagnosed with anti-LGI1 encephalitis during the acute phase, admitted to two tertiary hospitals in China between January 2022 and September 2024. Clinical data, neuroimaging findings, and follow-up outcomes were systematically analyzed. Results:The primary clinical manifestations included memory impairment, epileptic seizures, psychiatric and behavioral disturbances, sleep dysfunction, involuntary movements, faciobrachial dystonic seizures (FBDS), and autonomic dysfunction. Among 53 patients tested for thyroid function, 9 (17.0%) exhibited abnormalities. Hyponatremia was observed in 41 of 82 patients (50.0%), and hyperhomocysteinemia (HHCY) in 23 of 80 (28.7%). Among 68 patients who underwent cerebrospinal fluid (CSF) analysis, elevated intracranial pressure was observed in 10 (14.7%), pleocytosis in 22 (32.4%), and elevated protein levels in 27 (39.7%). Electrocardiographic abnormalities were identified in 26 of 42 patients (61.9%) without prior cardiovascular disease. MRI abnormalities were present in 75 of 80 patients (93.8%), most commonly affecting the temporal lobe (55.0%), hippocampus (51.2%), and amygdala (11.2%). PET imaging in 39 patients frequently revealed hypermetabolism in the basal ganglia and temporal lobe. All patients received first-line immunotherapy. Of the 63 patients with follow-up data, 59 (93.7%) achieved favorable outcomes. Conclusion:Anti-LGI1 encephalitis is an immune-mediated autoimmune disorder characterized by memory impairment, epileptic seizures, FBDS, psychiatric and behavioral disturbances, autonomic dysfunction, hyponatremia, and HHCY. Immunotherapy is generally effective, leading to favorable prognosis in the majority of patients.

AIMS:Anti-N-methyl-d-aspartate (Anti-NMDA) receptor encephalitis is characterized by widespread neural dysfunction, yet the underlying neurochemical and molecular mechanisms remain poorly understood. This study aimed to investigate whether functional alterations in anti-NMDAR encephalitis are spatially associated with neurotransmitter receptor distributions and transcriptomic profiles, to uncover their neurochemical, molecular, and cellular signatures. METHODS:A total of 25 patients diagnosed with anti-NMDA receptor encephalitis and 30 healthy controls (HCs) were recruited in this study. All participants underwent resting-state functional MRI (rs-fMRI) scanning, with patients being scanned during the recovery phase of the disease. To explore the neurochemical, molecular and cellular signatures underlying altered brain functional activity, we conducted neuroimaging-neurotransmitter, neuroimaging-transcriptome regression analyses and cell type enrichment analysis, linking aberrant fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) patterns with PET-derived receptor maps and transcriptomic profiles from the Allen Human Brain Atlas (AHBA). RESULTS:Patients exhibited significant alterations in fALFF/ReHo across the frontal, temporal, and occipital cortices. Neuroimaging-neurotransmitter regression analyses revealed that these functional abnormalities were significantly associated with neurotransmitter receptor maps, particularly involving serotonin (5-HT2a) and dopamine (D1) systems. Neuroimaging-transcriptome regression analyses further demonstrated that the genes associated with fALFF/ReHo alterations were primarily enriched in biological processes related to neuron projection development, oligodendrocyte specification and differentiation leading to myelin components for central nervous system. The oligodendrocytes and astrocytes were considered key cellular contributors to the functional alterations. CONCLUSIONS:Our findings demonstrate that neural dysfunction during the recovery phase of anti-NMDAR encephalitis are closely linked to neurotransmitter systems and transcriptomic profiles. This multiscale integration bridges molecular mechanisms with neural dysfunction and may inform novel therapeutic strategies.

Our study aimed to report the clinical features and epidemiological characteristics of hereditary transthyretin amyloidosis-polyneuropathy(ATTRv-PN) with TTR Ala97Ser(p.Ala117Ser) mutation from South Mainland China. We identified 21 patients from 20 families diagnosed with Ala97Ser ATTRv-PN based on strict clinical and electrophysiological criteria from three centers. Clinical and laboratory data were retrospectively retrieved for analysis. A gender imbalance was noted with a male-to-female ratio of 18:3. All patients showed late onset, with the age of onset at 56.5 ± 7.2 years. The predominant initial symptom, reported by 15 patients (71.4%), was numbness. Paraesthesia was present in all patients. Eighteen patients (85.7%) had autonomic dysfunction. Cardiac, renal, and ocular dysfunctions were noted in 17 (80.9%), 4(19.0%), and 4(19.0%) patients, respectively. Nerve conduction studies have shown axonal-type sensorimotor polyneuropathy. The decline in sensory nerve action potentials was more noticeable than in compound muscle action potentials. The nerve damage present in the lower limbs was more severe than that in the upper limbs. Nerve biopsy revealed positive Congo red staining in 11/15 patients (73.3%). ATTRv-PN appears relatively rare in South Mainland China, with our study providing the largest cohort of Ala97Ser mutation cases to date. We found a significant founder effect by combining the clinical and demographic characteristics. That helps us understand the gene's transmission pathway and lays the foundation for carrier screening and tertiary prevention and control. We also propose a new scoring model and demonstrate that this model allows the profiling of different genotypes of ATTRv-PN, facilitating early clinical detection and diagnosis.

Copper deficiency peripheral neuropathy caused by excessive treatment in Wilson’s disease has been reported. But its pathological characteristics are rarely reported. Here, we report a case of copper deficiency peripheral neuropathy in Wilson’s disease and present the characteristics of its nerve biopsy. A 44-year-old female patient diagnosed with Wilson’s disease was on long-term oral administration of zinc gluconate and copper chelators. In June 2022, she developed symptoms of peripheral neuropathy, accompanied by anemia and neutropenia. The 24-hour urinary copper excretion was 53.85 µg. Serum copper was 66.6 µg/L, and ceruloplasmin was 0.01 g/L. Electromyography showed length-dependent axonal damage in peripheral nerves. Sural nerve biopsy showed mainly axonal damage and decreased density of nerve fibres of all classes (large and small myelinated and unmyelinated), accompanied by demyelination. Ultimately, the diagnosis of copper deficiency peripheral neuropathy caused by excessive treatment of Wilson’s disease was established. After discontinuing copper chelation therapy, she experienced mild alleviation of symptoms. The pathological features of copper deficiency peripheral neuropathy in Wilson’s disease include the formation of axonal vacuoles, the presence of myelin ovoids, and a reduced number of large and small myelinated and unmyelinated nerve fibers. This case emphasizes the importance of monitoring copper metabolism during the stable phase of treatment for patients with Wilson’s disease.

Metastasis is a hallmark of advanced cancer, and the liver is a common site for secondary metastasis of many tumor cells, including colorectal, pancreatic, gastric, and prostate cancers. Macrophages in the tumor microenvironment (TME) promote tumor cell metastasis through various mechanisms, including angiogenesis and immunosuppression, and play a unique role in the development of liver metastasis. Macrophages are affected by a variety of factors. Under conditions of hypoxia and increased acidity in the TME, more factors are now found to promote the polarization of macrophages to the M2 type, including exosomes and amino acids. M2-type macrophages promote tumor cell angiogenesis through a variety of mechanisms, including the secretion of factors such as VEGF, IL-1β, and TGF-β1. M2-type macrophages are subjected to multiple regulatory mechanisms. They also interact with various cells within the tumor microenvironment to co-regulate certain conditions, including the creation of an immunosuppressive microenvironment. This interaction promotes tumor cell metastasis, drug resistance, and immune escape. Based on the advent of single-cell sequencing technology, further insights into macrophage subpopulations in the tumor microenvironment may help in exploring new therapeutic targets in the future. In this paper, we will focus on how macrophages affect the TME, how tumor cells and macrophages as well as other immune cells interact with each other, and further investigate the mechanisms involved in liver metastasis of tumor cells and their potential as therapeutic targets.

OBJECTIVE:Myasthenia gravis (MG) is an autoimmune disease characterized by disrupted neuromuscular synaptic transmission. Efgartigimod, a human Fc receptor antagonist, has been approved for patients with MG. Its potential use for other IgG-mediated neurological autoimmune diseases is unclear. This study aimed to retrospectively evaluate the efficacy and safety of efgartigimod in patients with neurological autoimmune diseases. METHODS:This retrospective study investigated patients with neurological autoimmune diseases who were treated with efgartigimod in the Henan Provincial People's Hospital. The efficacy of the medication was analyzed using the quality-of-life improvement score and the IgG level pre- and post-efgartigimod treatment. The safety of the medication was assessed by considering adverse events and blood parameters. The blood parameters, including routine blood parameters, coagulation, liver, kidney, and immune function. RESULTS:Seventeen patients received efgartigimod in the Henan Provincial People's Hospital from September 1, 2023, to January 31, 2024. In MG patients, myasthenia gravis activities of daily living (MG-ADL) reduced after efgartigimod treatment for 4 weeks compared with baseline (P < 0.05). Autoimmune encephalitis (AE) is a group of inflammatory disease with antibodies against neuronal synaptic and cell surface antigens. Similarly, patients with AE had a statistically significant reduction in modified Rankin scale (mRS) after efgartigimod treatment for 4 weeks compared with baseline (P < 0.05). Guillain Barre syndrome (GBS) is an immune-mediated disease of the peripheral nerves and nerve roots. However, the inflammatory neuropathy cause and treatment (INCAT) scale score didn't statistically differ in GBS patients before and after efgartigimod treatment (P > 0.05). The IgG levels significantly reduced after the first infusion and gradually decreased after multiple infusions (P < 0.05). Most subjects did not have increased IgG serum levels before treatment. IgA, IgM, and complement levels didn't differ significantly with efgartigimod treatment (P > 0.05). There were no changes in blood parameters during the treatment (P > 0.05). CONCLUSIONS:Efgartigimod was effective and safe in neurological IgG-mediated autoimmune diseases, even in patients without increased IgG serum levels.

Since 2017, human encephalitis caused by pseudorabies virus (PRV) has been reported in 28 cases in China. The clinical symptoms include fever, headache, seizures, focal neurological loss, disturbance of consciousness, etc.. This disease has the high disability rate and fatality rate. PRV is mainly transmitted through close contact with infected pigs or their excrement, or spread via blood-borne. Patients are mostly practitioners in the live pig industry chain. Early diagnosis and treatment are critical to the prognosis of patients. Therefore, this article reviews the progress on diagnosis and treatment of human encephalitis caused by PRV, in order to improve the clinical diagnosis and treatment of this disease.

BACKGROUND:Glioma is a common tumor that occurs in the brain and spinal cord. Hypoxia is a crucial feature of the tumor microenvironment. Tumor-associated macrophages/microglia play a crucial role in the advancement of glioma. This study aims to illuminate the detailed mechanisms by which hypoxia regulates microglia and, consequently, influences the progression of glioma. METHODS:The glioma cell viability and proliferation were analyzed by cell counting kit-8 assay and 5-ethynyl-2'-deoxyuridine assay. Wound healing assay and transwell assay were implemented to detect glioma cell migration and invasion, respectively. Enzyme-linked immunosorbent assay was conducted to detect protein levels in cell culture medium. The protein levels in glioma cells and tumor tissues were evaluated using western blot analysis. The histological morphology of tumor tissue was determined by hematoxylin-eosin staining. The protein expression in tumor tissues was determined using immunohistochemistry. Human glioma xenograft in nude mice was employed to test the influence of hypoxic microglia-derived interleukin-1beta (IL-1β) and heparanase (HPSE) on glioma growth in vivo. RESULTS:Hypoxic HMC3 cells promoted proliferation, migration, and invasion abilities of U251 and U87 cells by secreting IL-1β, which was upregulated by hypoxia-induced activation of hypoxia inducible factor-1alpha (HIF-1α). Besides, IL-1β from HMC3 cells promoted glioma progression and caused activation of nuclear factor-κB (NF-κB) and upregulation of HPSE in vivo. We also confirmed that IL-1β facilitated HPSE expression in U251 and U87 cells by activating NF-κB. Hypoxic HMC3 cells-secreted IL-1β facilitated the proliferation, migration, and invasion of U251 and U87 cells via NF-κB-mediated upregulation of HPSE expression. Finally, we revealed that silencing HPSE curbed the proliferation and metastasis of glioma in mice. CONCLUSION:Hypoxia-induced activation of HIF-1α/IL-1β axis in microglia promoted glioma progression via NF-κB-mediated upregulation of HPSE expression.