ObjectiveTo investigate the effects of Anmeidan （AMD） on neuroinflammation in the hippocampus of sleep-deprived rats. MethodsSD rats were randomly divided into four groups （n = 10 per group）： control group， model group， AMD group， and melatonin group. A sleep deprivation model was established using the modified multiple platform water environment method. The AMD group received AMD at a dose of 18.18 g·kg^-1·d^-1， the melatonin group received melatonin at 100 mg·kg^-1·d^-1， and the control and model groups were given an equal volume of pure water. All treatments were administered by gavage for four weeks. Spontaneous activity was assessed using an animal behavior video system. Serum levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） were measured by enzyme-linked immunosorbent assay （ELISA）. Hippocampal pyramidal neuron morphology was examined using hematoxylin-eosin （HE） staining， and ultrastructural changes of hippocampal neurons were observed via transmission electron microscopy. Immunofluorescence was used to detect the expression of brain-derived neurotrophic factor （BDNF） and nerve growth factor （NGF） in the hippocampus. Western blot analysis was performed to measure the expression of nuclear factor-κB （NF-κB）， phosphorylated NF-κB （p-NF-κB）， NOD-like receptor protein 3 （NLRP3）， and Caspase-1 proteins. ResultsCompared with the control group， the model group showed a significant increase in activity duration and frequency （P<0.01）， increased hippocampal pyramidal cell structural damage and decreased cell count， aggravated hippocampal ultrastructural damage， mitochondrial cristae disruption， and exacerbated vacuolization. The expression of p-NF-κB p65， NLRP3， and Caspase-1 proteins was upregulated， serum IL-1β， IL-6， and TNF-α levels were significantly elevated （P<0.01）， and the fluorescence intensity of BDNF and NGF proteins was significantly reduced （P<0.01）. Compared with the model group， the AMD group showed a significant reduction in activity duration and frequency （P<0.01）， increased hippocampal pyramidal cell count with reduced structural damage， alleviated hippocampal ultrastructural damage， significantly downregulated p-NF-κB p65， NLRP3， and Caspase-1 protein expression （P<0.01）， decreased serum IL-1β， IL-6， and TNF-α levels （P<0.01）， and significantly increased the fluorescence intensity of BDNF and NGF proteins （P<0.01）. ConclusionAnmeidan alleviates hippocampal neuronal damage in sleep-deprived rats， potentially by downregulating the NLRP3 signaling pathway， reducing inflammatory cytokine release， and increasing neurotrophic factor levels.

BackgroundSevere mental disorders represent a major public health concern due to the high disability rates and substantial disease burden， which has garnered significant national attention and prompted their inclusion in public health project management systems. However， credible evidence regarding the current status of disease management and factors influencing disease stabilization among patients with severe mental disorders in Luzhou City， Sichuan Province， remains limited. ObjectiveTo investigate the current management status of patients with severe mental disorders in Luzhou City， Sichuan Province， and to analyze influencing factors of disease stabilization among patients under standardized care， so as to provide evidence-based insights for developing targeted management strategies to optimize clinical interventions for this patient population. MethodsIn March 2023， data were extracted from the Sichuan Mental Health Service Comprehensive Management Platform for patients with severe mental disorders in Luzhou City who received management between December 2017 and December 2022. Information on mental health service utilization and clinical status changes was collected. Trend analysis was conducted to evaluate temporal changes in key management indicators for severe mental disorders in Luzhou City. Logistic regression analysis was employed to identify factors influencing the disease stabilization or fluctuation of these patients. ResultsThis study enrolled a total of 20 232 patients. In Luzhou City， the stabilization rate and standardized management rate of severe mental disorders were 94.89% and 79.36% in 2017， respectively， which increased to 95.33% and 96.92% by 2022. The regular medication adherence rate rose from 34.42% in 2018 to 86.81% in 2022. In 2022， the regular medication adherence rate was 71.80% for schizophrenia， 55.26% for paranoid psychosis， and 51.43% for schizoaffective disorder. Multivariate analysis identified the following protective factors for disease stabilization： age of 18~39 years （OR=0.613， 95% CI： 0.409~0.918）， age of 40~65 years （OR=0.615， 95% CI： 0.407~0.931）， urban residence （OR=0.587， 95% CI： 0.478~0.720）， and regular medication adherence （OR=0.826， 95% CI： 0.702~0.973）. Risk factors for disease fluctuation included poor （OR=1.712， 95% CI： 1.436~2.040）， non-inclusion in care-support programs （OR=1.928， 95% CI： 1.694~2.193）， non-participation in community rehabilitation （OR=2.255， 95% CI： 1.930~2.634）， and intermittent medication adherence （OR=3.893， 95% CI： 2.548~5.946）. ConclusionThe stability rate， standardized management rate， and regular medication adherence rate of patients with severe mental disorders in Luzhou City have shown a year-by-year increase. Age， household registration status， economic condition， medication compliance， and community-based rehabilitation were identified as influencing factors for disease fluctuation in these patients. ［Funded by Luzhou Science and Technology Plan Project （number， 2022-ZRK-186）］

To summarize the applications of data-intelligence technology in diagnosing lysosomal storage disease(LSD), analyze their opportunities and challenges in clinical practice as well as their development trends, and provide insights and recommendations for advancing digitally driven auxiliary diagnostic technologies.

To review the randomized controlled trials (RCTs) at home and abroad on digital intelligence (DI)-driven rehabilitation in patients of neuromuscular disease, compare the effects of DI-driven rehabilitation with traditional rehabilitation, summarize the special needs and challenges faced by patients in rehabilitation of rare neuromuscular diseases, and provide evidence for the development and quality improvement of rehabilitation for rare neuromuscular diseases.

To provide references to and give suggestions to the development and optimiza-tion of Digital Intelligence (DI) technology in management of non-hospitalized patients by systematical review the application of digital technology in non-hospital settings.

ObjectiveJunctophilin-2 (JPH2) is an essential structural protein that maintains junctional membrane complexes (JMCs) in cardiomyocytes by tethering the plasma membrane to the sarcoplasmic reticulum, thereby facilitating excitation-contraction (E-C) coupling. Mutations in JPH2 have been associated with hypertrophic cardiomyopathy (HCM), but the molecular mechanisms governing its membrane-binding properties and the functional relevance of its membrane occupation and recognition nexus (MORN) repeat motifs remain incompletely understood. This study aimed to elucidate the structural basis of JPH2 membrane association and its implications for HCM pathogenesis. MethodsA recombinant N-terminal fragment of mouse JPH2 (residues1-440), encompassing the MORN repeats and an adjacent helical region, was purified under near-physiological buffer conditions.X-ray crystallography was employed to determine the structure of the JPH2 MORN-Helix domain. Sequence conservation analysis across species and junctophilin isoforms was performed to assess the evolutionary conservation of key structural features. Functional membrane-binding assays were conducted using liposome co-sedimentation and cell-based localization studies in COS7 and HeLa cells. In addition, site-directed mutagenesis targeting positively charged residues and known HCM-associated mutations, including R347C, was used to evaluate their effects on membrane interaction and subcellular localization. ResultsThe crystal structure of the mouse JPH2 MORN-Helix domain was resolved at 2.6 Å, revealing a compact, elongated architecture consisting of multiple tandem MORN motifs arranged in a curved configuration, forming a continuous hydrophobic core stabilized by alternating aromatic residues. A C-terminal α-helix further reinforced structural integrity. Conservation analysis identified the inner groove of the MORN array as a highly conserved surface, suggesting its role as a protein-binding interface. A flexible linker segment enriched in positively charged residues, located adjacent to the MORN motifs, was found to mediate direct electrostatic interactions with negatively charged phospholipid membranes. Functional assays demonstrated that mutation of these basic residues impaired membrane association, while the HCM-linked R347C mutation completely abolished membrane localization in cellular assays, despite preserving the overall MORN-Helix fold in structural modeling. ConclusionThis study provides structural insight into the membrane-binding mechanism of the cardiomyocyte-specific protein JPH2, highlighting the dual roles of its MORN-Helix domain in membrane anchoring and protein interactions. The findings clarify the structural basis for membrane targeting via a positively charged linker and demonstrate that disruption of this interaction—such as that caused by the R347C mutation—likely contributes to HCM pathogenesis. These results not only enhance current understanding of JPH2 function in cardiac E-C coupling but also offer a structural framework for future investigations into the assembly and regulation of JMCs in both physiological and disease contexts.

BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

Panax quinquefolium, also known as American ginseng, is a perennial herb in the Araliaceae family. It has the effects of replenishing Qi and nourishing Yin, clearing heat and generating saliva. Additionally, it has protective effects on the nerves, improves myocardial ischemia and hypoxia, regulates metabolism, enhances the body's immunity, and is known as "green gold". However, with the development of the industry and the expansion of planting scales, P. quinquefolium faces serious disease issues that are difficult to prevent and control. Among these, root rot, often referred to as "plant cancer", is one of the most destructive plant diseases affecting the yield and quality of P. quinquefolium. P. quinquefolium root rot is caused by the fungi Fusarium(genus) and Ilyonectria(genus), which severely affect the root system and limit the production and quality of P. quinquefolium, thus restricting the development of the P. quinquefolium industry. In recent years, research on P. quinquefolium root rot has attracted significant attention and made some progress. However, the mechanisms of interaction between the root rot pathogens and the host plant remain unclear. This paper reviews the research progress on the pathogens, infection cycle, disease prevalence, pathogenesis, and biological control of P. quinquefolium root rot to provide prospects for future research, aiming to provide references for the in-depth study and effective control of root rot, and to promote the green and healthy development of the P. quinquefolium industry.
Panax/microbiology* ; Plant Diseases/prevention & control* ; Plant Roots/microbiology* ; Fusarium/pathogenicity*

This study compared the differences in intestinal absorption characteristics of eleven active components in Rubus multibracteatus(RM) extract(protocatechuic acid, tiliroside, scutellarin, luteoloside, astragalin, epicatechin, catechin, xanthotoxin, p-coumaric acid, caffeic acid, and apigenin-7-O-glucuronide) between normal rats and inflammatory pain model rats using the in-vitro everted intestinal sac model. The RM extract was administered at absorption concentrations of 25.0, 50.0, and 100.0 mg·mL~(-1). The contents of the eleven components in intestinal absorption solution samples were quantified by ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS), and their cumulative absorption(Q) and absorption rate constant(K_a) were calculated to evaluate the absorption characteristics of these components in normal rats and inflammatory pain model rats. The results show that except for catechin, epicatechin, and caffeic acid, the cumulative absorption-time curves of the other eight components(protocatechuic acid, tiliroside, scutellarin, luteoloside, astragalin, xanthotoxin, p-coumaric acid, and apigenin-7-O-glucuronide) exhibit an upward trend without saturation, with correlation coefficients(R~2) all > 0.9, indicating linear absorption. However, the overall absorption of all components is not dose-dependent with increasing concentration, suggesting that their absorption mechanisms are not solely passive diffusion. In both normal and model rats, the jejunum shows the highest absorption for all components except xanthotoxin. The overall absorption of seven components(excluding protocatechuic acid, caffeic acid, apigenin-7-O-glucuronide, and luteoloside) in normal rats is better than that in model rats across all intestinal segments. These findings indicate that the pathological state of inflammatory pain alters the intestinal absorption of RM extract, and its mechanism needs further investigation.
Animals ; Rats ; Intestinal Absorption/drug effects* ; Male ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/metabolism* ; Disease Models, Animal ; Pain/metabolism* ; Intestines/drug effects* ; Intestinal Mucosa/metabolism*