ObjectiveTo investigate the possible mechanism of Jishe Qushi Capsule （脊蛇祛湿胶囊， JQC） in treating rheumatoid arthritis （RA） from the perspective of macrophage polarization mediated by neutrophil extracellular traps （NETs）. MethodsTwenty-four female SD rats were randomly divided into four groups， blank control group， model group， JQC group， and peptidylarginine deiminase 4 （PAD4） inhibitor group with 6 rats in each group. All groups but the blank control group were subjected to the induction of collagen-induced arthritis （CIA）. After successful model establishment， rats in the JQC group received intragastric administration of JQC 1.47 g/kg daily； rats in the PAD4 inhibitor group received intraperitoneal injections of the PAD4 inhibitor 4 mg/kg weekly. Rats in the blank， model， and PAD4 inhibitor groups received 2 ml of pure water daily by gavage. All treatments lasted 4 weeks. Joint lesions of each group were assessed on day 7， 14， 21， 28， and 35 after model establishment， and arthritis index （AI） scores were recorded. At 24 h after the final administration， histopathology of knee joints， including HE staining， safranin O-fast green staining， and TRAP staining， was performed. Flow cytometry was used to detect the counts of M1 and M2 macrophages in peripheral blood. ELISA was used to determine serum levels of TRACP， NETs， TNF-α， IL-1β， and iNOS. Western Blotting and qRT-PCR were used to measure MPO， NE， RANKL， OPG， and p65 protein and mRNA expression in knee cartilage tissue. ResultsCompared with the blank control group， the model group showed increased AI scores （P＜0.05）， marked synovial inflammatory infiltration， angiogenesis， and bone-cartilage destruction， increased TRAP-positive osteoclasts， increased M1 macrophages and decreased M2 macrophages， elevated serum TRACP， NETs， TNF-α， IL-1β， and iNOS （P＜0.05）， elevated MPO， NE， RANKL， and p65 protein/mRNA expression and decreased OPG protein/mRNA expression in knee cartilage tissue （P＜0.05）. Compared with the model group， the JQC group exhibited improved synovial inflammation， angiogenesis， and bone-cartilage damage， reduced AI scores on day 21， 28， and 35， decreased osteoclast counts， decreased M1 macrophages and increased M2 macrophages， reduced serum TRACP， NETs， TNF-α， IL-1β， and iNOS （P＜0.05）， decreased MPO， NE， RANKL， and p65 protein/mRNA expression and increased OPG expression （P＜0.05）. Compared with the PAD4 inhibitor group， the JQC group showed significantly lower AI scores， reduced M1 macrophages， increased M2 macrophages （P＜0.05）， reduced serum TRACP， TNF-α， IL-1β， and iNOS， decreased MPO， RANKL， and p65 expression， and increased OPG levels （P＜0.05）. ConclusionThe therapeutic mechanism of JQC for RA may involve inhibition of NETs formation， downregulation of the RANKL/NF-κB signaling pathway， and regulation of macrophage M1/M2 polarization imbalance， thereby suppressing osteoclastogenesis and inflammatory bone destruction.

Lung cancer is a leading cause of cancer-related morbidity and mortality worldwide. Coupled with the substantial workload, the clinical management of lung cancer is challenged by the critical need to efficiently and accurately process increasingly complex medical information. In recent years, large language models (LLMs) technology has undergone explosive development, demonstrating unique advantages in handling complex medical data by leveraging its powerful natural language processing capabilities, and its application value in the field of lung cancer diagnosis and treatment is continuously increasing. The paper systematically analyzes that the exceptional potential of LLMs in lung cancer auxiliary diagnosis, tumor feature extraction, automatic staging, progression/outcome analysis, treatment recommendations, medical documentation generation, and patient education. However, they face critical technical and ethical challenges including inconsistent performance in complex integrated decision-making (e.g., TNM staging, personalized treatment suggestions) and "black box" opacity issues, along with dilemmas such as training data biases, model hallucinations, data privacy concerns, and cross-lingual adaptation challenges ("data colonization"). Future directions should prioritize constructing high-quality multimodal corpora specific to lung cancer, developing interpretable and compliant specialized models, and achieving seamless integration with existing clinical workflows. Through dual drivers of technological innovation and ethical standardization, LLMs should be prudently advanced for holistic lung cancer management processes, ultimately promoting efficient, standardized, and personalized diagnosis and treatment practices.

To investigate the efficacy and safety of glucocorticoids combined with cyclophosphamide (CTX) and rituximab (RTX) in elderly patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis with renal involvement.

ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

Background Amid global climate change, extreme environmental events are occurring more frequently, and it is imperative to investigate the impacts of combined exposure to fine particluate matter (PM_2.5) and cold spells (CS) on population mortality. Objective To analyze the association between sequential extreme PM_2.5-cold spell (EP-CS) events and non-accidental mortality among residents in Zigong City from 2016 to 2021. Methods Using time-series study design, meteorological data in Zigong were collected from the Zigong Meteorological Bureau for the period from January 1, 2016 to December 31, 2021, while daily non-accidental mortality data were obtained from the mortality surveillance system of the Zigong Center for Disease Control and Prevention. We adopted the percentile method to define extreme PM_2.5 events and cold spells. We analyzed the risk effect of EP-CS events on non-accidental mortality among residents in this city and explored the potential amplification of damage resulting from different patterns of consecutive extreme events by using distributed lag nonlinear model (DLNM). We also conducted stratified analyses based on age, gender, education level, and marital status. Results The EP-CS events demonstrated a significant impact on non-accidental mortality among the local residents, exhibiting a certain lagged effect. The effects on the overall residents lasted from lag0 (RR=1.030, 95%CI: 1.013, 1.048) to lag14 (RR=1.035, 95%CI: 1.019, 1.052). Notably, the effects were more pronounced among females, individuals aged 65 years and above, and those who were never married, divorced, or widowed. Different patterns of EP-CS events all associated with adverse effects, the health impact of EP-CS events was significantly greater than that of individual PM_2.5 pollution or CS events. The analysis of lag effects across different event patterns revealed that the overall effect of EP-CS events with shorter intervals (0–7 d) had a stronger effect compared to EP-CS with longer intervals (8–14 d), and the RR values of lag14 were 1.034 (95%CI: 1.015, 1.054) and 1.017 (95%CI: 1.007, 1.027), suggesting that the damaging effect of compound events occurring in the short term was more significant. Conclusion All sequential extreme EP-CS events have an impact on non-accidental mortality among residents in this city, with compound events demonstrating a stronger effect. Females, individuals aged ≥65 years, and those who were never married, divorced, or widowed are more sensitive to EP-CS events.

Accommodative dysfunction, particularly accommodative lag, acts as a core hub connecting near work activity to myopic axial elongation. This review thoroughly explores the multidimensional biological mechanisms by which accommodative function drives axial growth. In addition to the classic pathway where hyperopic defocus signals induce retinal-choroidal-scleral biochemical remodeling, two other mechanisms are highlighted: a biomechanical pathway involving direct mechanical traction on the equatorial sclera caused by sustained ciliary muscle contraction, and a neural pathway where abnormal accommodative micro fluctuations degrade retinal image quality, thereby triggering abnormal ocular growth. Based on these comprehensive mechanisms, this paper systematically analyzes the principles of pharmacological(atropine), optical(orthokeratology, defocus lenses), and vision therapy interventions. Myopia progression results from the integrated regulation of optical defocus, mechanical stress, and neural dynamics. Future myopia control should advance toward precise, personalized combination strategies tailored to individual accommodative and genetic profiles.

ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

ObjectiveTo investigate the association of hepatic steatosis with the level of viral replication and the progression of hepatic fibrosis in patients with chronic hepatitis B （CHB） through a real-world study， and to determine the independent influencing factors for hepatic fibrosis. MethodsA total of 887 CHB patients who attended the outpatient service and inpatient ward of Hepatology in The First Affiliated Hospital of Dalian Medical University from July 2021 to March 2025 were enrolled as subjects， and according to the presence or absence of metabolic dysfunction-associated steatotic liver disease （MASLD）， they were divided into CHB group with 560 patients and CHB+MASLD group with 327 patients. The association between hepatic steatosis and HBV load in CHB patients was analyzed， as well as the impact of varying degrees of hepatic steatosis on hepatic fibrosis. The t-test or the Mann-Whitney U test was used for comparison of continuous data between groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups； a Spearman correlation analysis was performed； a Logistic regression analysis was used to investigate influencing factors. ResultsThe patients enrolled received antiviral therapy according to viral load； of all patients， 275 （31%） received nucleos（t）ide analogue combined with pegylated interferon-α， 532 （60%） received nucleos（t）ide analogue monotherapy， and 80 （9%） did not receive antiviral therapy. A total of 44 patients （5.0%） who were receiving PEG-IFN-α therapy and had marked thrombocytopenia were excluded， and finally 843 patients were included for comparison of aspartate aminotransferase-to-platelet ratio index （APRI） and fibrosis-4 index （FIB-4）. Compared with the CHB group， the CHB+MASLD group had a significantly higher proportion of male patients （χ²=5.917， P<0.05） and a significant increase in CAP value （t=21.646， P<0.05）. The median values of liver function parameters for the population enrolled were within the normal range， and no significant inflammatory activity was observed. The virological analysis showed that compared with the CHB group， the CHB+MASLD group had significantly lower serum level of pregenomic RNA （Z=-2.894， P<0.05） and HBeAg positivity rate （χ²=8.725， P<0.05）， and CAP was significantly negatively correlated with pgRNA （r=-0.117， P<0.05）. In the HBeAg-negative subgroup， compared with the CHB group， the CHB+MASLD group had a significantly lower level of hepatitis B surface antigen （Z=-0.765， P<0.05）； in the HBeAg-positive subgroup， the CHB+MASLD group had a significantly higher level of HBV DNA than the CHB group （Z=-2.509， P<0.05）. The analysis of hepatic fibrosis showed that the CHB+MASLD group had significantly lower values of APRI （Z=-3.418， P<0.05） and FIB-4 （Z=-6.237， P<0.05）. Compared with the CHB group， the CHB+MASLD S1 group had a significantly higher proportion of patients without fibrosis and a significantly lower proportion patients with liver cirrhosis （χ²=7.935， P<0.05）； in the CHB+MASLD S2 group， there was no significant difference in the proportion of patients with different fibrosis stages； the CHB+MASLD S3 group had a significantly lower proportion of patients without fibrosis and a significantly higher proportion of patients with early-stage fibrosis （χ²=9.101， P<0.05）. The Logistic regression analysis showed that an increase in CAP （odds ratio ［OR］=1.08， 95% confidence interval ［CI］： 1.03 — 1.13， P<0.05）， an increase in age （OR=1.02， 95%CI： 1.01 — 1.04， P<0.05）， male sex （OR=1.77， 95%CI： 1.19 — 2.64， P<0.05）， an increase in HBV DNA （OR=1.35， 95%CI： 1.15 — 1.57， P<0.001）， an increase in aspartate aminotransferase （OR=1.02， 95%CI： 1.01 — 1.03， P<0.001）， and an increase in gamma-glutamyl transpeptidase （OR=1.00， 95%CI： 1.00 — 1.01， P=0.028） were independent influencing factors for hepatic fibrosis. The risk of hepatic fibrosis in S3 patients was higher than that in patients without steatosis （OR=5.05， 95%CI： 2.48 — 10.29， P<0.001）. ConclusionThere is a lower level of HBV replication in CHB patients comorbid with MASLD. Hepatic steatosis is associated with HBV-related virological markers and the progression of hepatic fibrosis， and severe fatty liver disease may promote the progression of hepatic fibrosis in CHB patients.

BACKGROUND:Spinal cord injury is a neurological disorder caused by traumatic or non-traumatic events,often leading to severe functional impairment below the injured segment.In recent years,neural stem cell transplantation has been considered to have significant therapeutic potential in regulating the inflammatory response after spinal cord injury,inhibiting excessive proliferation of glial scars,and promoting nerve regeneration. OBJECTIVE:To review and discuss the potential mechanism of action of acupuncture and neural stem cell transplantation therapy in inhibiting spinal cord injury-induced secondary injury,and to delve into the scientific basis for its treatment of spinal cord injury. METHODS:PubMed,Elsevier,WanFang,and CNKI databases were searched using"spinal cord injury,acupuncture,neural stem cells,SDF-1α/CXCR4 axis"as Chinese and English search terms.Totally 96 articles were finally included.The research findings of acupuncture combined with neural stem cells in the treatment of spinal cord injury were summarized and analyzed,and the mechanism of this combination therapy in the treatment of secondary injury after spinal cord injury was summarized. RESULTS AND CONCLUSION:(1)The stromal-derived factor 1α(SDF-1α)/chemokine receptor 4(CXCR4)axis plays a crucial role in neural stem cell transplantation for spinal cord injury.This signaling mechanism not only affects neural stem cell migration,proliferation,and differentiation,but is also a key factor in determining the efficiency of stem cell homing to the injury site.Therefore,the regulation of targeting this axis is of great significance in enhancing the therapeutic effect of spinal cord injury.(2)Acupuncture,as a traditional Chinese medicine therapy,shows unique advantages in the regulation of secondary injury in spinal cord injury.It can effectively reduce secondary injury after spinal cord injury by regulating inflammatory response,inhibiting apoptosis,improving microcirculation,reducing glial scar formation,and counteracting oxidative stress.(3)Acupuncture was also able to influence the expression and function of the SDF-1α/CXCR4 axis,thereby enhancing the homing and survival ability of neural stem cells and promoting nerve regeneration and functional recovery.(4)The therapy combining acupuncture and stem cell transplantation is an innovative treatment strategy for spinal cord injury and suitable for repairing neural circuits.It combines the wisdom of traditional Chinese medicine with the advantages of modern biotechnology,providing a new treatment option for spinal cord injury patients.However,this combination therapy is still in the research and exploration stage,and its long-term efficacy and safety need to be further verified.(5)Taken together,acupuncture and neural stem cell transplantation for the treatment of spinal cord injury has great potential for clinical application,but in-depth research and optimization of treatment options are still needed.In the future,we look forward to further revealing the efficacy mechanism and optimal indications of this therapy through more clinical trials and mechanism studies,so as to bring better hope of recovery and more efficient therapeutic effects to spinal cord injury patients.

Objective To analyze the cognitive function and sleep quality of the elderly in Shanghai community, and explore the related influencing factors. Methods A stratified cluster random sampling method was used to select 8 community health centers in Shanghai for a questionnaire survey, including 3 677 elderly individuals who completed the “Comprehensive Health Status Survey of Elderly Residents in Shanghai” from September 2023 to November 2023. Basic information of the elderly was collected, including age, gender, education level, smoking, drinking, mahjong playing behavior, and exercise habits. The Pittsburgh sleep quality index (PSQI) was used to assess the sleep quality of the elderly, subjective cognitive decline (SCD) self-assessment questionnaire and Mini-Mental State Examination (MMSE) were used to evaluate cognitive function, while the Hamilton Anxiety Scale (HAMA) and patient health questionnaire-9 (PHQ-9) were used to assess anxiety and depression levels, and the mini nutritional assessment (MNA) was used to evaluate nutritional status. According to the MMSE scores, the elderly were divided into three groups: no cognitive impairment (MMSE ≥ 27), mild cognitive impairment (MMSE 21-26), and moderate to severe cognitive impairment (MMSE ≤ 20). The general data, lifestyle habits, and scale scores of the three groups were compared. Ordered logistic regression was used to analyze the influencing factors of sleep quality. Results There were statistically significant differences in age, gender, waist circumference, body mass index (BMI), education level, pet ownership, smoking, drinking, mahjong playing behavior, exercise habits, and scale scores among the three groups (P＜0.05). Logistic regression analysis showed that age, waist circumference, gender, drinking habits, mahjong playing behavior, and chronic comorbidities are influencing factors for the PSQI grading in the elderly (P＜0.05). The MMSE score (OR＝1.037, P＝0.001), SCD score (OR＝1.123, P＜0.001), HAMA score (OR＝1.183, P＜0.001), PHQ-9 score (OR＝1.249, P＜0.001) are positive influencing factors for PSQI grading, while the MNA score is a negative influencing factor (OR＝0.960, P＝0.037). Conclusions Advanced age, female gender, low education level, no pet ownership, no mahjong playing behavior, no exercise habits, and poor sleep quality are risk factors for cognitive impairment in the elderly. Advanced age, female gender, no mahjong playing behavior and poor nutritional status are influencing factors for poor sleep quality in the elderly, and severe comorbidities, anxiety, depression, and subjective decline in cognitive function all affect sleep quality.