Feng Qiu

Amyotrophic lateral sclerosis (ALS) is biologically heterogeneous, and oxidative injury can contribute to degeneration while also reflecting downstream damage or adaptive responses. Glutathione S-transferase Pi 1 (GSTP1) combines glutathione-dependent detoxification with non-canonical regulation of c-Jun N-terminal kinase (JNK), but the biochemical evidence for direct GSTP1–JNK coupling largely comes from non-ALS systems. This narrative review separates human ALS observations, functional ALS-model findings, and extrapolated mechanisms. Altered GSTP1 abundance or total GST activity in ALS does not establish GSTP1-specific impairment or causality. JNK-related injury has stronger functional support in selected ALS models involving DLK/MAP3K12, ASK1, HIPK2, and MAP4K4. Ferroptosis-related findings are concentrated in SOD1 models, with additional evidence of susceptibility in FUS cellular models, and do not establish a GSTP1–JNK–ferroptosis cascade. We distinguish neuronal and glial context and the execution of apoptosis versus ferroptosis. Decisive tests combine GSTP1 perturbation with catalytic and interaction-deficient rescue, direct binding and JNK-activity assays, and pathway-specific cell-death rescue. GSTP1 remains a candidate context-dependent modifier of shared neurodegenerative processes; causal validation, reproducible pathway biomarkers, and safety assessment are required before therapeutic translation.

Background: Primary intramedullary spinal cord lymphoma (PISCL) is extremely rare and often mimics inflammatory myelopathy. To our knowledge, concurrent acute ischemic stroke has not previously been described in PISCL. Case presentation: A 60-year-old man developed an initial lacunar infarct (Day 0), followed by rapidly progressive bilateral lower-limb weakness (Day 7) and a thoracic intramedullary lesion with minimal cerebrospinal fluid (CSF) inflammation. A presumptive diagnosis of transverse myelitis was made, and corticosteroid and intravenous immunoglobulin therapy produced only transient improvement. On Day 9, he developed a new right middle cerebral artery (MCA) stroke requiring mechanical thrombectomy. At Week 7, follow-up spinal MRI demonstrated a new focal intramedullary lesion at T3 with homogeneous enhancement, and PET-CT showed focal hypermetabolism, leading to biopsy confirmation of diffuse large B-cell lymphoma (DLBCL) with an immunohistochemically defined triple-expressor phenotype. Treatment with rituximab, high-dose methotrexate, ibrutinib, and radiotherapy was initiated. Outcome: Despite therapy, neurological function worsened, and the patient progressed to paraplegia. Conclusion: This case highlights the diagnostic challenges of PISCL presenting as inflammatory myelopathy and supports consideration of earlier tissue diagnosis when the clinical course is progressive and steroid responsiveness is only transient. The accompanying ischemic stroke may have reflected multiple contributing factors, but causality cannot be established from a single case. The immunohistochemically defined triple-expressor phenotype should be interpreted cautiously in the absence of cytogenetic confirmation of MYC/BCL2/BCL6 rearrangements.

Immune dysregulation is involved in Parkinson's disease (PD), but the roles of C‐X‐C motif chemokine receptor 3 (CXCR3)/chemokine receptor 6 (CXCR6) on T cells and their correlation with peripheral inflammation remain unclear. This study investigated their expression on peripheral blood T cells and correlation with inflammation in PD. A total of 36 PD patients and 26 healthy controls were enrolled; their clinical information and laboratory test results (including the systemic immunoinflammatory index [SII], neutrophil‐to‐lymphocyte ratio [NLR], monocyte‐to‐lymphocyte ratio [MLR], platelet‐to‐lymphocyte ratio [PLR], monocyte‐to‐high‐density lipoprotein ratio [MHR], and erythrocyte distribution width over platelets ratio [RPR]) were recorded. Meanwhile, a multicolour flow cytometry protocol using six cell surface antibodies (CD3, CD4, CD8, CD45RO, CXCR3, and CXCR6) was applied. The results showed that CD8 ⁺ T cells were significantly reduced in the PD group compared with healthy controls ( p < 0.001), and CXCR3 expression was significantly increased on peripheral blood CD4 ⁺ effector T cells and CD8 ⁺ T cells of PD patients ( p < 0.001). Additionally, CXCR6 expression was significantly elevated on cytotoxic T lymphocytes (CTLs) ( p < 0.0001) but showed no significant difference on CD4 ⁺ T cells between PD patients and controls ( p > 0.05). Compared with healthy controls, PD patients had significantly increased peripheral blood C‐reactive protein (CRP) levels ( p < 0.001) but remarkably decreased monocytes, lymphocytes, and MHR ( p < 0.01). Collectively, the upregulated expression of CXCR3 and CXCR6 predominantly on CD8 ⁺ T lymphocytes may contribute to PD pathogenesis, though no significant correlation between the expression of these receptors and peripheral inflammation was observed.

Background: The pathogenesis of myasthenia gravis (MG) involves an imbalance of various pro-inflammatory and anti-inflammatory cytokines. Currently, there are no clinical studies comparing the effects of hormones and different non-hormonal immunosuppressants on the regulation of plasma cytokines. Hence, there is no unified standard for drug selection. This study aims to explore the associations between glucocorticoid (GC), tacrolimus (TAC), and rituximab (RTX) and plasma cytokine levels in generalized myasthenia gravis, providing an observational overview of how different treatment regimens relate to immune-inflammatory patterns in clinical practice. Methods: A retrospective collection of 65 GMG patients diagnosed at the Department of Neurology, General Hospital of the People’s Liberation Army from July 2022 to May 2024 was conducted. According to treatment regimens, patients were divided into a GC group ( n = 17), a TAC group ( n = 17), a RTX group ( n = 9), and non-medicated patients (NM) group ( n = 22), another 30 healthy individuals were selected as the healthy control (HC) group. Clinical data and levels of cytokines such as Interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17, Tumor Necrosis Factor (TNF)- α , Interferon (IFN)-α, and IFN- γ in plasma were collected to compare plasma cytokine levels across the three treatment groups and the non-medicated group. Results: Compared with the HC group, GMG patients in the NM group showed significantly higher plasma levels of IL-1β, IL-2, IL-4, IL-10, IL-17, TNF- α , IFN- α , and IFN- γ . Relative to the NM group, the GC group exhibited lower levels of IL-1β, IL-4, IL-6, IL-17, and TNF-α, and the RTX group showed lower levels of IL-1β, IL-4, IL-6, IFN- α , and TNF-α. In the comparison across treatment groups, the GC group presented lower IL-17 and IFN- γ levels than the TAC group, while the RTX group presented lower IL-6, IFN-α, and TNF-α levels than the TAC group. Conclusion: Cytokine levels were markedly elevated in the plasma of patients with GMG, indicating their potential involvement in disease-related immune dysregulation. Distinct treatment groups displayed different cytokine patterns, reflecting heterogeneous immunological states among patients receiving GC, TAC, or RTX. Collectively, these findings provide preliminary immunological insights into GMG and highlight the need for validation in larger, prospective studies.

Objective: This study aimed to evaluate the long-term efficacy and safety of the fully human anti-CD20 monoclonal antibody ofatumumab in refractory generalized myasthenia gravis, with focus on its potential to promote recovery of neuromuscular junction transmission function. Methods: Fourteen refractory patients treated at the Eighth Medical Center of the Chinese PLA General Hospital from March 2023 to June 2024 were included. All had relapsed after maintaining Minimal Manifestation Status for over 1 year and showed inadequate response to immunosuppressants. Ofatumumab 20 mg was administered at weeks 0, 1, 2, and 4, followed by additional doses every 4–6 months according to symptoms and CD19-positive B-cell reconstitution. Low-frequency 3-Hz repetitive nerve stimulation of the facial, accessory, and axillary nerves was conducted at baseline and month 12. MG-ADL, QMG, MGC scores and B-cell and T-cell levels were monitored. Results: The compound muscle action potential (CMAP) decrement of the predominantly involved nerve and the mean decrement across the three tested nerves improved at month 12, indicating enhanced neuromuscular junction transmission. MG-ADL, QMG, and MGC scores declined from month 1, with earlier improvement in bulbar, limb, and neck muscle groups. All patients discontinued corticosteroids by month 12 while remaining clinically stable. B cells stayed at low levels, whereas T-cell counts showed no significant change. Treatment was well tolerated. Conclusion: Ofatumumab provides durable clinical benefit and steroid-sparing effects, and its sustained depletion of CD20-positive B cells may facilitate recovery of neuromuscular junction transmission. These findings support its potential application within the field of regenerative pharmacology.

Cerebral infarction, a cerebrovascular disorder, is characterized by the sudden onset of neurological deficits and clinical symptoms. It ranks among the leading causes of death and severe disability worldwide. The etiology of cerebral infarction is multifaceted, with common risk factors including dietary patterns, smoking, hypertension, and diabetes mellitus. In recent years, the role of the gut microbiota in systemic immunity and tumorigenesis has been intensively explored, thrusting the research on the gut—brain axis into the spotlight. However, there is a lack of literature investigating the relationship between the gut microbiota and blood metabolites in cerebral infarction. In this study, we employed 16S rRNA analysis and ultra—high—performance liquid chromatography—tandem mass spectrometry (UHPLC—MS/MS) for a comprehensive metagenomic and metabolomic analysis of fecal samples from cerebral infarction patients and the general population. Our results revealed a significant correlation between the gut microbiome and serum metabolites, highlighting the impact of the microbiome on metabolic pathways. Specifically, we found that 35 gut microbiome taxa, such as Actinobacteriota and Peptostreptococcales—Tissierellales, were significantly enriched in the control group (N group). Through Linear Discriminant Analysis Effect Size (LEfSe) analysis, 72 taxa showed significant differences between cerebral infarction patients and healthy individuals. Among them, 22 key taxa were identified as microbial biomarkers for differentiating patients from healthy controls. These findings suggest that variations in the microbiome and metabolites could potentially serve as biomarkers for future diagnostic and therapeutic strategies in cerebral infarction.

Background: Non-small cell lung cancer (NSCLC) has high incidence and mortality rates. The discovery of an effective biomarker for predicting prognosis and treatment response in patients with NSCLC is of great significance. Bacterial lipopolysaccharide-related genes (LRGs) play a critical role in tumor development and the formation of an immunosuppressive microenvironment; however, their relevance in NSCLC prognosis and immune features is yet to be discovered.Methods: Differentially expressed LRGs associated with NSCLC prognosis were identified in the TCGA dataset. Prognostic LRG scoring and nomogram models were established using single-variable Cox regression, Least Absolute Shrinkage, and Selection Operator (LASSO) regression. The prognostic value of the scoring and nomogram models was evaluated using Kaplan-Meier (KM) analysis and further validated using an external dataset. Patients were stratified into high- and low-risk groups based on the nomogram score, and drug sensitivity analysis was performed. Additionally, clinical characteristics, mutation features, immune infiltration characteristics, and responses to immunotherapy were compared between the two groups.Results: We identified 15 differentially expressed LRGs associated with NSCLC prognosis. A prognostic prediction model consisting of 6 genes (VIPR1, NEK2, HMGA1, FERMT1, SLC7A, and TNS4) was established. Higher LRG scores were associated with worse clinical prognosis and were independent prognostic factors for NSCLC. Subsequently, a clinical risk prediction nomogram model for NSCLC was constructed, incorporating the status of patients with tumor burden, tumor T-stage, and LRG scores. The nomogram model demonstrated good predictive performance upon validation. Additionally, NSCLC patients classified as high risk based on the model’s predictions exhibited not only a poorer prognosis but also a more pronounced inflammatory immune microenvironment phenotype than low-risk patients. Furthermore, high-risk patients showed disparate predicted responses to various drugs and immunotherapies compared with low-risk patients.Conclusion: The LRGs scoring model can serve as a biomarker that contributes to the establishment of a reliable prognostic risk-prediction model, potentially facilitating the development of personalized treatment strategies for patients with NSCLC.

Imaging Photoplethysmography (IPPG) is an emerging and efficient optical method for non-contact measurement of pulse waves using an image sensor. While the contactless way brings convenience, the inevitable distance between the sensor and the subject results in massive specular reflection interference on the skin surface, which leads to a low Signal to Interference plus Noise Ratio (SINR) of IPPG. To ease this challenge, this work proposes a novel modulation illumination approach to measure the accurate arterial pulse wave via surface reflection interference isolation from IPPG. Based on the proposed skin reflection model, a specific modulation illumination is designed to separate the surface reflections and obtain the subcutaneous diffuse reflections containing the pulse wave information. Compared with the results under ambient illumination and constant supplemental illumination, the SINR of the proposed method is improved by 4.56 and 3.74 dB, respectively.