The paper reports one case of primary cutaneous amyloidosis (PCA) treated by tapping with plum-blossom needle combined with sulfur ointment and local irradiation. PCA in this case was manifested as generalized erythema, papules, plaques, lichenification, and severe pruritus. In treatment, tapping with plum-blossom needle was delivered at typical lesions to induce local congestion, redness, and minimal bleeding. After cleaned with sterile gauze for 10 s, 25% sulfur ointment was evenly applied, followed by local irradiation with a TDP lamp for 15 min. This session was repeated twice a week. In 1 month of treatment, the lesions turned flat and the skin was soft as the normal, with pigmentation and mild pruritus left. In 3 months of follow-up, no papules recurred, and mild pruritus presented occasionally.
Humans ; Ointments/administration & dosage* ; Sulfur/administration & dosage* ; Skin Diseases, Genetic/radiotherapy* ; Middle Aged ; Amyloidosis, Familial/radiotherapy* ; Male ; Acupuncture Therapy/instrumentation* ; Female ; Combined Modality Therapy

Membrane-bound organelles and membraneless organelles (MLOs) coordinate various biological processes within eukaryotic cells. Among these, stress granules (SGs) are significant cytoplasmic MLOs that form in response to cellular stress, exhibiting liquid-like properties alongside stable substructures. SGs interact with diverse organelles, thereby influencing cellular pathways that are critical in both health and disease contexts. This review discusses the interplay between SGs and organelles and explores the methodologies employed to analyze interactions between SGs and other MLOs. Furthermore, it highlights the pivotal roles SGs play in regulating cellular responses and the pathogenesis of amyotrophic lateral sclerosis. Gaining insights into these interactions is essential for deciphering the mechanisms underlying both physiological processes and pathological conditions.
Humans ; Stress Granules/pathology* ; Organelles/metabolism* ; Amyotrophic Lateral Sclerosis/pathology* ; Animals ; Stress, Physiological ; Cytoplasmic Granules/metabolism*

Dementia is a neurodegenerative disease closely related to brain network dysfunction. In this study, we assessed the interdependence between brain regions in patients with early-stage dementia based on phase-lock values, and constructed a functional brain network, selecting network feature parameters for metrics based on complex network analysis methods. At the same time, the entropy information characterizing the EEG signals in time domain, frequency domain and time-frequency domain, as well as the nonlinear dynamics features such as Hjorth and Hurst indexes were extracted, respectively. Based on the statistical analysis, the feature parameters with significant differences between different conditions were screened to construct feature vectors, and finally multiple machine learning algorithms were used to realize the recognition of early categories of dementia patients. The results showed that the fusion of multiple features performed well in the categorization of Alzheimer's disease, frontotemporal lobe dementia and healthy controls, especially in the identification of Alzheimer's disease and healthy controls, the accuracy of β-band reached 98%, which showed its effectiveness. This study provides new ideas for the early diagnosis of dementia and computer-assisted diagnostic methods.
Humans ; Electroencephalography/methods* ; Alzheimer Disease/physiopathology* ; Dementia/physiopathology* ; Early Diagnosis ; Algorithms ; Brain/physiopathology* ; Machine Learning ; Frontotemporal Dementia/physiopathology* ; Diagnosis, Computer-Assisted

Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder characterized by progressive axonopathy, jointly leading to the dying back of the motor neuron, disrupting both nerve signaling and motor control. In this review, we highlight the roles of axonopathy in ALS progression, driven by the interplay of multiple factors including defective trafficking machinery, protein aggregation, and mitochondrial dysfunction. Dysfunctional intracellular transport, caused by disruptions in microtubules, molecular motors, and adaptors, has been identified as a key contributor to disease progression. Aberrant protein aggregation involving TDP-43, FUS, SOD1, and dipeptide repeat proteins further amplifies neuronal toxicity. Mitochondrial defects lead to ATP depletion, oxidative stress, and Ca²⁺ imbalance, which are regarded as key factors underlying the loss of neuromuscular junctions and axonopathy. Mitigating these defects through interventions including neurotrophic treatments offers therapeutic potential. Collaborative research efforts aim to unravel ALS complexities, opening avenues for holistic interventions that target diverse pathological mechanisms.
Humans ; Amyotrophic Lateral Sclerosis/therapy* ; Animals ; Axons/metabolism* ; Mitochondria/metabolism* ; Motor Neurons/pathology*

Background: Amyotrophic lateral sclerosis is one of the neurodegenerative disorders with very limited treatment options owing to its progressive course and diverse pathophysiology. Majority of patients succumb to death within three to five years after the onset of symptoms, mostly due to respiratory failure. This study aimed to determine the efficacy and safety of ultra-high dose methylcobalamin versus placebo among patients with early-stage amyotrophic lateral sclerosis in terms of slowing down functional decline. Methods: MEDLINE, CENTRAL, and Google Scholar databases were searched from inception up to September 23, 2023. The impact of treatments was measured by risk ratios with 95% confidence interval. The overall certainty of the evidence was evaluated using GRADE. Results: No significant difference was detected for the outcome median change in the ALSFRS-R score for the whole cohort. Post-hoc analyses showed that ultra-high-dose methylcobalamin decreased ALSFRS-R scores (p=0.003 for 50 mg and p=0.01 for all methylcobalamin groups) in a dose-responsive manner. Mean difference was 1.97 in favor of methylcobalamin (95% CI, 0.44- 3.50; P = .01). Conclusion Ultra-high dose methylcobalamin can reduce ALSFRS-R scores of patients in its early stage but the scarcity of clinical trials makes it difficult to support a robust conclusion. Ultra-high dose methylcobalamin therapy remains to be investigational.
Amyotrophic Lateral Sclerosis ; Systematic Review

Patients with amyotrophic lateral sclerosis ( ALS ) often have difficulty in expressing their intentions through language and behavior, which prevents them from communicating properly with the outside world and seriously affects their quality of life. The brain-computer interface (BCI) has received much attention as an aid for ALS patients to communicate with the outside world, but the heavy device causes inconvenience to patients in the application process. To improve the portability of the BCI system, this paper proposed a wearable P300-speller brain-computer interface system based on the augmented reality (MR-BCI). This system used Hololens2 augmented reality device to present the paradigm, an OpenBCI device to capture EEG signals, and Jetson Nano embedded computer to process the data. Meanwhile, to optimize the system's performance for character recognition, this paper proposed a convolutional neural network classification method with low computational complexity applied to the embedded system for real-time classification. The results showed that compared with the P300-speller brain-computer interface system based on the computer screen (CS-BCI), MR-BCI induced an increase in the amplitude of the P300 component, an increase in accuracy of 1.7% and 1.4% in offline and online experiments, respectively, and an increase in the information transfer rate of 0.7 bit/min. The MR-BCI proposed in this paper achieves a wearable BCI system based on guaranteed system performance. It has a positive effect on the realization of the clinical application of BCI.
Humans ; Amyotrophic Lateral Sclerosis ; Brain-Computer Interfaces ; Quality of Life ; Event-Related Potentials, P300 ; Wearable Electronic Devices

Objective To determine the diagnostic accuracy of the intensity of fasciculation evaluated by muscle ultrasound in the differential diagnosis of amyotrophic lateral sclerosis (ALS). Methods We prospectively recruited patients who had ALS and neuropathy-radiculopathy attending Peking Union Medical College Hospital from 2017 to 2020. Healthy adults from a community were recruited as healthy controls. Muscle strength was assessed using the Medical Research Council (MRC) scale. At the first visit to the hospital, patients were assessed for maximal grade of fasciculations, total fasciculation score, and fasciculation grade in 16 muscle groups of bilateral upper and lower limbs using ultrasonography. The sensitivity and specificity of maximal grade of fasciculations, total fasciculation score, and fasciculation grade for the diagnosis of ALS were assessed by receiver operating characteristic analyses. Results The percentage of limb muscles with a maximal fasciculation grade higher than grade 2 in ALS patients and neuropathy-radiculopathy patients was 84.9% and 9.8%, respectively (χ² = 172.436, P < 0.01). Of the 16 limb muscles detected, the total fasciculation score [median (interquartile range)] was 29 (15, 41) in ALS patients and 3 (0, 8) in neuropathy-radiculopathy patients (Z = 9.642, P < 0.001). Remarkable fasciculations were seen in ALS patients whose muscles with a MRC score ranging from 2 to 4, followed by patients with MRC score 5, and then in those with MRC score 0 and 1. The sensitivity and specificity of total fasciculation score for diagnosis of ALS were 80.6% and 93.4%, respectively (cut-off value 14). In patients with ALS, for muscles with MRC score 4 and 5, the percentage of muscles with fasciculation grades ≥ 3 was 42.3% and 24.1% respectively, while in neuropathy-radiculopathy patients, the percentage for muscles with MRC score 4 and 5 was only 1.7% and 0, respectively. Conclusion A combined analysis of fasciculation intensity and MRC score of the limb muscles may be helpful for differential diagnosis of ALS.
Adult ; Humans ; Amyotrophic Lateral Sclerosis/diagnostic imaging* ; Fasciculation/diagnostic imaging* ; Radiculopathy ; Muscle, Skeletal/diagnostic imaging* ; Ultrasonography/methods*

Humans ; Amyotrophic Lateral Sclerosis/drug therapy* ; Neurons ; Phosphatidylinositol 3-Kinases

A decline in the activities of oxidative phosphorylation (OXPHOS) complexes has been consistently reported in amyotrophic lateral sclerosis (ALS) patients and animal models of ALS, although the underlying molecular mechanisms are still elusive. Here, we report that receptor expression enhancing protein 1 (REEP1) acts as an important regulator of complex IV assembly, which is pivotal to preserving motor neurons in SOD1^G93A mice. We found the expression of REEP1 was greatly reduced in transgenic SOD1^G93A mice with ALS. Moreover, forced expression of REEP1 in the spinal cord extended the lifespan, decelerated symptom progression, and improved the motor performance of SOD1^G93A mice. The neuromuscular synaptic loss, gliosis, and even motor neuron loss in SOD1^G93A mice were alleviated by increased REEP1 through augmentation of mitochondrial function. Mechanistically, REEP1 associates with NDUFA4, and plays an important role in preserving the integrity of mitochondrial complex IV. Our findings offer insights into the pathogenic mechanism of REEP1 deficiency in neurodegenerative diseases and suggest a new therapeutic target for ALS.
Mice ; Animals ; Amyotrophic Lateral Sclerosis/metabolism* ; Superoxide Dismutase-1/metabolism* ; Superoxide Dismutase/metabolism* ; Mice, Transgenic ; Spinal Cord/pathology* ; Mitochondria/physiology* ; Disease Models, Animal

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons in the brain and spinal cord. One important aspect of ALS pathogenesis is superoxide dismutase 1 (SOD1) mutant-mediated mitochondrial toxicity, leading to apoptosis in neurons. This study aimed to evaluate the neural protective synergistic effects of ginsenosides Rg1 (G-Rg1) and conditioned medium (CM) on a mutational SOD1 cell model, and to explore the underlying mechanisms. We found that the contents of nerve growth factor, glial cell line-derived neurotrophic factor, and brain-derived neurotrophic factor significantly increased in CM after human umbilical cord mesenchymal stem cells (hUCMSCs) were exposed to neuron differentiation reagents for seven days. CM or G-Rg1 decreased the apoptotic rate of SOD1^G93A-NSC34 cells to a certain extent, but their combination brought about the least apoptosis, compared with CM or G-Rg1 alone. Further research showed that the anti-apoptotic protein Bcl-2 was upregulated in all the treatment groups. Proteins associated with mitochondrial apoptotic pathways, such as Bax, caspase 9 (Cas-9), and cytochrome c (Cyt c), were downregulated. Furthermore, CM or G-Rg1 also inhibited the activation of the nuclear factor-kappa B (NF-κB) signaling pathway by reducing the phosphorylation of p65 and IκBα. CM/G-Rg1 or their combination also reduced the apoptotic rate induced by betulinic acid (BetA), an agonist of the NF-κB signaling pathway. In summary, the combination of CM and G-Rg1 effectively reduced the apoptosis of SOD1^G93A-NSC34 cells through suppressing the NF-κB/Bcl-2 signaling pathway (Fig. 1 is a graphical representation of the abstract).
Humans ; NF-kappa B/metabolism* ; Ginsenosides/pharmacology* ; Amyotrophic Lateral Sclerosis/genetics* ; Culture Media, Conditioned/pharmacology* ; Superoxide Dismutase-1 ; Neurodegenerative Diseases ; Neurons/metabolism* ; Apoptosis