The inflammatory microenvironment is closely associated with the initiation and progression of osteoarthritis （OA）， specifically manifesting as macrophage activation， dysregulation of inflammatory cytokines， and redox imbalance. Following an overview of the pathological characteristics of the OA inflammatory microenvironment， this paper reviews the research progress on the mechanism of traditional Chinese medicine （TCM） intervening in OA by modulating the inflammatory microenvironment. It has been found that TCM monomers/active ingredients （such as total alkaloids from Strychnos nux-vomica ， quercetin， triptolide， etc.）， herb pairs （e.g. Angelica pubescens - Gentiana macrophylla ， Carthami Flos-Lycopodii Herba）， and TCM formulas （such as Zhuanggu jianxi formula， Duhuo jisheng decoction and Rongjin niantong formula， etc.） can inhibit macrophage activation， reduce the release of proinflammatory cytokines and the generation of reactive oxygen species by inhibiting multiple signaling pathways， including nuclear factor-κB， Wnt/ β -catenin， and mitogen-activated protein kinase， thereby alleviating the articular inflammatory microenvironment， restoring local joint homeostasis， and slowing the progression of OA.

Objective: To explore the distribution of traditional Chinese medicine (TCM) syndromes in patients with interstitial lung disease (ILD) and its influencing factors. Methods: This cross-sectional study included 385 patients with ILD admitted to the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine) from January 2018 to June 2022. Data on sex, age, body mass index, smoking history, respiratory rate, hospitalization time, treatment cost, whether velcro rales can be heard, comorbidities with rheumatic immune diseases, TCM four examination information, and clinical examination results, including CT imaging, D-dimer level, and lung function-related indicators, were collected. The distribution pattern of TCM syndromes in patients with ILD and the association between TCM syndromes and clinical indicators were analyzed using the cluster analysis and binary Logistic regression analysis. Results: Among the 385 patients with ILD, sticky phlegm (59.74%) and shortness of breath (56.10%) were common symptoms, while greasy tongue coating (55.32%), red tongue (52.73%), and slippery and rapid pulse (25.71%) were common tongue and pulse manifestations. The patients were divided into five syndromes using cluster analysis: syndrome of phlegm-heat stagnation in the lung (36.62%), syndrome of turbid phlegm obstructing lung (29.35%), syndrome of deficiency of both qi and yin (12.99%), syndrome of qi deficiency of lung and kidney (11.95%), and syndrome of phlegm and blood stasis obstructing lung (9.09%). The D-dimer level was lower in patients with syndrome of phlegm-heat stagnation in the lung, syndrome of turbid phlegm obstructing lung, syndrome of deficiency of both qi and yin, and syndrome of qi deficiency of lung and kidney than in those with syndrome of phlegm and blood stasis obstructing lung (P<0.05). The percentage of predicted forced vital capacity (FVC%pred) of patients with syndrome of phlegm-heat stagnation in the lung, syndrome of turbid phlegm obstructing lung, syndrome of deficiency of both qi and yin, and syndrome of phlegm and blood stasis obstructing lung was higher than in those with syndrome of qi deficiency of lung and kidney (P<0.05). Among patients aged 60 and above, those with syndrome of phlegm-heat stagnation in the lung, syndrome of phlegm and blood stasis obstructing lung, and syndrome of deficiency of both qi and yin containing dual pathogenic syndrome elements were more likely to experience moderate to severe pulmonary diffusion impairment than those with syndrome of turbid phlegm obstructing lung and syndrome of qi deficiency of lung and kidney containing single pathogenic syndrome elements (P<0.05). The Logistic regression showed that the FVC%pred was an influential factor for syndrome of qi deficiency of lung and kidney, and the area under the receiver operating characteristic (ROC) curve (AUC) between FVC%pred and the formation of syndrome of qi deficiency of lung and kidney was 0.676 (95%CI: 0.598-0.755), P=0.002. The sensitivity was 0.431, the specificity was 0.966, and the best threshold on the ROC curve of 0.397 was 79.1%. The D-dimer level was an influential factor in the formation of syndrome of phlegm and blood stasis obstructing lung. The AUC between D-dimer level and the formation of syndrome of phlegm and blood stasis obstructing lung was 0.729 (95%CI: 0.655-0.802), P<0.001. The sensitivity was 0.914, the specificity was 0.523, and the best threshold on the ROC curve of 0.437 was 0.675 mg/L. Conclusion syndrome of phlegm-heat stagnation in the lung and syndrome of turbid phlegm obstructing lung are common among patients with ILD. Complex pathological syndromes are more likely to exacerbate pulmonary diffusion dysfunction. The FVC%pred can assist in differentiating syndrome of qi deficiency of lung and kidney, whereas the D-dimer level can assist in differentiating syndrome of phlegm and blood stasis obstructing lung.

Objective To study the latent classification of medical service utilization behaviors among middle-aged and older chronic disease patients,providing a theoretical basis for the allocation of medical resources.Methods Using data from the 2018 China Health and Retirement Longitudinal Study(CHARLS)database,latent class analysis was employed to conduct subgroup analysis on the medical choice preferences of middle-aged and older chronic disease patients.Logistic regression was used to analyze the influence of various factors on medical preference subgroups.Results The medical choice preferences of middle-aged and older chronic disease patients were classified into three latent subgroups:public hospital treatment preference type,non-public hospital treatment preference type,and public hospital consultation preference type.Compared to the public hospital treatment preference type,patients under 60 years old(OR=0.456,P=0.034),those living in rural areas(OR=0.256,P=0.006),and those with smoking habits(OR=3.11,P＜0.001)were more inclined to choose non-public hospitals for treatment.In contrast,patients over 60 years old(OR=1.916,P=0.015),those with an education level of primary school or above(OR=2.595,P=0.004),and those with smoking habits(OR=2.591,P=0.044)tended to choose public hospitals for consultation or physical examinations.Conclusion Currently,private hospitals play an increasingly prominent role in chronic disease treatment.However,the utilization rate of traditional Chinese medicine among middle-aged and older chronic disease pa-tients is relatively low,and health awareness remains weak.It is recommended to strengthen the regulation of private hospitals,enhance the credibility and accessibility of traditional Chinese medicine,and intensify health education in communities to meet the growing health demands of middle-aged and older chronic disease patients.

Objective:To develop and validate the stroke recovery phase patient active exercise guidance satisfaction rat-ing scale(SRPPAEGSRS)for stroke recovery patients.Method:Using the self-determination theory as the primary framework,integrated with the Brunnstrom stag-ing and social cognitive theories,an initial scale was developed through literature review,semi-structured inter-views,expert consultations,and a preliminary survey.A convenience sampling of 434 stroke patients in the re-covery phase who visited or were hospitalized in the rehabilitation department of a tertiary hospital in Guizhou province from November 2024 to February 2025 were recruited.Reliability and validity tests were conducted to finalize the scale.Result:A total of 422 valid questionnaires were collected,with an effective response rate of 97.24%.The scale consisted of 2 parts,8 dimensions,and 18 items.Three rounds of expert consultations showed a 100%positive coefficient,Kendall's harmony coefficient>0.5,authority coefficient>0.7,and coefficient of varia-tion<0.280.The critical ratio(CR)for all items in each part and the total scale was>8.The correlation coef-ficients between item scores and total scores for each part and the total scale were>0.6.The item-level con-tent validity index(I-CVI)was>0.8,and the scale-level content validity index(S-CVI)was>0.9.Exploratory factor analysis yielded a cumulative variance contribution rate of 77.895%,with no cross-loadings.Confirmatory factor analysis indicated good model fit(χ2/df=1.250,RMSEA=0.034,CFI=0.935,GFI=0.915).The Cronbach's α coefficient,split-half reliability,and test-retest reliability for each part and the total scale were all>0.8.Conclusion:The scale demonstrated good reliability and validity,enabling systematic assessment stroke patients'needs and acceptance of active exercise guidance during recovery.Additionally,it quantifies patients'satisfac-tion with active exercise guidance through the"need-acceptance"discrepancy and identifies bottlenecks in their active rehabilitation.

OBJECTIVE: To explore the effect and mechanism of acupuncture at "Weizhong" (BL40) on microcirculation of paravertebral skeletal muscle in rats with chronic blunt injury of lumbar muscle based on the insulin-like growth factor-1 (IGF-1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway. METHODS: Forty-eight SPF-grade SD rats were randomized into a blank group (8 rats) and a modeling group (40 rats). Chronic blunt injury model was established by weight impact method in the modeling group. Forty rats were successfully modeled, and were randomly divided into a model group, an acupuncture at Weizhong group (Weizhong group), an acupuncture at non-acupoint group (non-acupoint group), an inhibitor group, and an inhibitor+acupuncture at Weizhong group (inhibitor+Weizhong group), 8 rats in each group. In the Weizhong group and the inhibitor+Weizhong group, acupuncture was applied at bilateral "Weizhong" (BL40). In the non-acupoint group, acupuncture was applied at non-acupoints, i.e. points 0.5 cm inward from bilateral "Weizhong" (BL40). The acupuncture intervention was delivered 20 min each time, once a day for continuous 2 weeks. In the inhibitor group and the inhibitor+Weizhong group, intraperitoneal injection of IGF-1 receptor (IGF-1R) inhibitor was given once a day, at a dosage of 2 mg/100 g, for continuous 2 weeks. Before modeling and on the 1st, 7th and 14th days of intervention, the body mass was measured. Before and after modeling, and after intervention, the limb grip strength and paw withdrawal threshold (PWT) were measured. After intervention, the morphology of psoas muscle was observed by HE staining; the ultrastructure of psoas muscle capillaries was observed by electron microscopy; the levels of serum vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) were detected by ELISA; and the protein and mRNA expression of IGF-1, IGF-1R, PI3K, AKT of psoas muscle was detected by Western blot and real-time PCR. RESULTS: Compared with the blank group, in the model group, the body mass on the 7th and 14th days of intervention, the limb grip strength, and the PWT of left and right hind feet were decreased (P<0.001, P<0.01); the skeletal muscle cells showed enlarged intercellular space, loosely arranged and irregularly shaped, the capillaries in the psoas muscle tissues were edematous, and the lumen of the blood vessels was obviously atrophied; the levels of serum VEGF and eNOS were decreased (P<0.001); in psoas muscle, the protein expression of IGF-1 and IGF-1R, as well as the p-PI3K/PI3K, p-AKT/AKT values were decreased (P<0.001), the mRNA expression of IGF-1, IGF-1R, PI3K and AKT was decreased (P<0.001, P<0.05). Compared with the model group, in the Weizhong group, the body weight was increased on the 7th and 14th days of intervention (P<0.001), the limb grip strength and the PWT of the left and right hind feet were increased (P<0.001, P<0.01); the arrangement of the skeletal muscle cells was relatively tight and the intercellular space was reduced, the blood vessels tended to be regular and the structure of the basement membrane was continuous, while the lumens of blood vessels were collapsed locally; the levels of serum VEGF and eNOS were increased (P<0.001); in psoas muscle, the protein expression of IGF-1 and IGF-1R, as well as the p-PI3K/PI3K, p-AKT/AKT values were increased (P<0.001), the mRNA expression of IGF-1, IGF-1R, PI3K and AKT was increased (P<0.001, P<0.01). Compared with the model group, in the inhibitor group, the body mass was decreased on the 7th and 14th days of intervention (P<0.05, P<0.01); the limb grip strength and the PWT of the left hind foot were decreased (P<0.01, P<0.001); the intercellular space of skeletal muscle cells was larger, the nuclei of the cells and erythrocytes were scattered in the intercellular space, the damage of the capillaries in the muscular tissues was serious, the collagen fibers were sparsely distributed and disorganized; the levels of serum VEGF and eNOS were decreased (P<0.001, P<0.01); in psoas muscle, the protein expression of IGF-1 and IGF-1R, as well as the p-PI3K/PI3K and p-AKT/AKT values were decreased (P<0.01, P<0.05, P<0.001), the mRNA expression of IGF-1, IGF-1R, PI3K, and AKT was decreased (P<0.01, P<0.001, P<0.05). Compared with the Weizhong group, in the non-acupoint group and the inhibitor+Weizhong group, the body mass was decreased on the 7th and 14th days of intervention (P<0.001, P<0.01), the limb grip strength was decreased (P<0.001); the morphology of muscle cell was relatively poor, with generally irregular, there was mild collapse and atrophy in the vascular lumen, and mild edema in the endothelial cells; the levels of serum VEGF and eNOS were decreased (P<0.001); in psoas muscle, the protein expression of IGF-1 and IGF-1R, as well as the p-PI3K/PI3K and p-AKT/AKT values were decreased (P<0.01, P<0.001), the mRNA expression of IGF-1, IGF-1R, PI3K, and AKT was decreased (P<0.001, P<0.01, P<0.05). Compared with the Weizhong group, the PWT of the left hind foot was decreased in the non-acupoint group (P<0.001), and PWT of the left and right hind feet was decreased in the inhibitor+Weizhong group (P<0.001). CONCLUSION Acupuncture at "Weizhong" (BL40) promotes lumbar muscle repair in chronic low back pain, its mechanism may be related to the activation of the IGF-1/PI3K/AKT pathway, thereby improving the microcirculation.
Animals ; Insulin-Like Growth Factor I/genetics* ; Acupuncture Therapy ; Rats, Sprague-Dawley ; Rats ; Proto-Oncogene Proteins c-akt/genetics* ; Male ; Humans ; Muscle, Skeletal/metabolism* ; Signal Transduction ; Phosphatidylinositol 3-Kinases/genetics* ; Wounds, Nonpenetrating/metabolism* ; Acupuncture Points

Chimeric antigen receptor T (CAR-T) cells have reshaped the treatment landscape of hematological malignancies, offering a potentially curative option for patients. Despite these major milestones in the field of immuno-oncology, growing experience with CAR-T cells has also highlighted several limitations of this strategy. The production process of CAR-T cells is complex, time-consuming, and costly, thus leading to poor drug accessibility. The potential carcinogenic risk of viral transfection systems remains a matter of controversy. Treatment-related side effects, such as cytokine release syndrome, can be life-threatening. And the biggest challenge is the inadequate efficacy related to poor infiltration and retention of CAR-T cells in tumor tissues and impaired T cell activation caused by the immunosuppressive tumor microenvironment (TME). Innovative strategies are urgently needed to address these problems, and nanomedicine offers good solutions to these challenges. In this review, we provide a comprehensive summary of recent advancements in the application of nanomaterials to enhance CAR-T cell therapy. We examine the role of innovative nanoparticle-based delivery systems in the production of CAR-T cells, with a particular focus on polymeric delivery systems and lipid nanoparticles (LNPs). Furthermore, we explore various strategies for delivering immune stimulators, which significantly enhance the efficacy of CAR-T cells by modulating T cell viability and functionality or by reprogramming the immunosuppressive TME. In addition, we discuss several novel therapeutic approaches aimed at mitigating the adverse effects associated with CAR-T therapies. Finally, we offer an integrated perspective on the future challenges and opportunities facing CAR-T therapies.
Humans ; Nanomedicine/methods* ; Receptors, Chimeric Antigen/metabolism* ; Immunotherapy, Adoptive/methods* ; T-Lymphocytes/immunology* ; Nanoparticles/chemistry* ; Animals

Objective To study the latent classification of medical service utilization behaviors among middle-aged and older chronic disease patients,providing a theoretical basis for the allocation of medical resources.Methods Using data from the 2018 China Health and Retirement Longitudinal Study(CHARLS)database,latent class analysis was employed to conduct subgroup analysis on the medical choice preferences of middle-aged and older chronic disease patients.Logistic regression was used to analyze the influence of various factors on medical preference subgroups.Results The medical choice preferences of middle-aged and older chronic disease patients were classified into three latent subgroups:public hospital treatment preference type,non-public hospital treatment preference type,and public hospital consultation preference type.Compared to the public hospital treatment preference type,patients under 60 years old(OR=0.456,P=0.034),those living in rural areas(OR=0.256,P=0.006),and those with smoking habits(OR=3.11,P＜0.001)were more inclined to choose non-public hospitals for treatment.In contrast,patients over 60 years old(OR=1.916,P=0.015),those with an education level of primary school or above(OR=2.595,P=0.004),and those with smoking habits(OR=2.591,P=0.044)tended to choose public hospitals for consultation or physical examinations.Conclusion Currently,private hospitals play an increasingly prominent role in chronic disease treatment.However,the utilization rate of traditional Chinese medicine among middle-aged and older chronic disease pa-tients is relatively low,and health awareness remains weak.It is recommended to strengthen the regulation of private hospitals,enhance the credibility and accessibility of traditional Chinese medicine,and intensify health education in communities to meet the growing health demands of middle-aged and older chronic disease patients.

Optical coherence tomography(OCT)based on near-infrared light backscattering or reflection,offers an extremely high resolution up to 10 μm.OCT technology has been widely applied in the field of coronary artery disease,but its application in cerebrovascular disease awaits further exploration.Current studies indicate that OCT holds unique advantages in the diagnosis and treatment of ischemic cerebrovascular diseases,including precise plaque characterization,postoperative stent surveillance,and long-term follow-up management.In cases of hemorrhagic cerebrovascular diseases,OCT can assist in evaluating the morphological characteristics of intracranial aneurysms,rupture risk,treatment efficacy,and recurrence.Furthermore,preliminary studies suggest OCT holds potential application value in evaluation of cerebral venous disorders.Future high-quality clinical studies are warranted to further elucidate OCT's clinical value in cerebrovascular disease management and establish standardized application criteria.

ObjectiveTo elucidate the potential mechanism of modified Sinisan （MSNS） in alleviating anxiety-like behaviors induced by chronic restraint stress （CRS） in mice at the metabolic level based on serum untargeted metabolomics and identify key metabolites and metabolic pathways regulated by MSNS. MethodsSeventy-two male C57BL/6 mice were randomly assigned into six groups： control， model， high-dose （2.4 g·kg^-1） MSNS， medium-dose （1.2 g·kg^-1） MSNS， low-dose （0.6 g·kg^-1） MSNS， and positive control （fluoxetine， 2.6 mg·kg^-1）. Except the control group， the other groups were subjected to CRS for the modeling of anxiety. Mice were administrated with corresponding agents by gavage 2 h before daily restraint for 14 days. Anxiety-like behaviors were evaluated by the open field test （OFT）， elevated plus maze （EPM） test， and light/dark box （LDB） test. Serum levels of corticotropin-releasing hormone （CRH）， adrenocorticotrophic hormone （ACTH）， and corticosterone （CORT） were measured via ELISA to assess stress levels. Ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） was employed to detect 9 metabolites in the brain tissue and serum metabolites. Orthogonal partial least squares-discriminant analysis （OPLS-DA） was adopted to identify differential metabolites （VIP>1.0， P<0.05）. MetaboAnalyst 5.0 was used for metabolic pathway enrichment analysis of the differential metabolites. ResultsCompared with the control group， the model group showed reductions in the central activity time and central distance in the OFT （P<0.05）， the proportions of open-arm residence time and open-arm residence times in the EPM test （P<0.01）， and the proportions of open box activity time and open box activity distance in the LDB test （P<0.05）， which were increased in the medium- and high-dose MSNS groups compared with the model group （P<0.05）. Compared with the control group， the model group showed elevated levels of CRH， ACTH， and CORT in the serum （P<0.01）， and the elevations were diminished in the medium- and high-dose MSNS groups （P<0.05）. UPLC-MS results indicated that compared with the control group， the model group presented declined DA， GABA， 5-HIAA， 5-HT， and 5-HT/Trp levels （P<0.05， P<0.01） and raised Glu， NE， Kyn， and Kyn/Trp levels （P<0.05）. Compared with the model group， high-dose MSNS increased the GABA， 5-HIAA， and 5-HT/Trp levels （P<0.05） and lowered the Glu and Kyn/Trp levels （P<0.05）. Untargeted metabolomics identified that 16 CRS-induced metabolic disturbances were reversed by MSNS. KEGG pathway analysis indicated that MSNS primarily modulated eight core pathways including alanine/aspartate/glutamate metabolism， butyrate metabolism， arginine-proline metabolism， TCA cycle， unsaturated fatty acid biosynthesis， and tryptophan metabolism. The mechanisms involved multidimensional biological processes， including neurotransmitter homeostasis regulation， TCA cycle energy metabolism optimization， and inflammatory response suppression. ConclusionMSNS alleviates CRS-induced anxiety-like behaviors in mice by mitigating hypothalamic-pituitary-adrenal axis hyperactivity， improving hippocampal neurotransmitter and tryptophan metabolic pathways， and regulating alanine/aspartate/glutamate metabolism， butyrate metabolism， arginine-proline metabolism， and TCA cycle.

ObjectiveTo elucidate the potential mechanism of modified Sinisan （MSNS） in alleviating anxiety-like behaviors induced by chronic restraint stress （CRS） in mice at the metabolic level based on serum untargeted metabolomics and identify key metabolites and metabolic pathways regulated by MSNS. MethodsSeventy-two male C57BL/6 mice were randomly assigned into six groups： control， model， high-dose （2.4 g·kg^-1） MSNS， medium-dose （1.2 g·kg^-1） MSNS， low-dose （0.6 g·kg^-1） MSNS， and positive control （fluoxetine， 2.6 mg·kg^-1）. Except the control group， the other groups were subjected to CRS for the modeling of anxiety. Mice were administrated with corresponding agents by gavage 2 h before daily restraint for 14 days. Anxiety-like behaviors were evaluated by the open field test （OFT）， elevated plus maze （EPM） test， and light/dark box （LDB） test. Serum levels of corticotropin-releasing hormone （CRH）， adrenocorticotrophic hormone （ACTH）， and corticosterone （CORT） were measured via ELISA to assess stress levels. Ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） was employed to detect 9 metabolites in the brain tissue and serum metabolites. Orthogonal partial least squares-discriminant analysis （OPLS-DA） was adopted to identify differential metabolites （VIP>1.0， P<0.05）. MetaboAnalyst 5.0 was used for metabolic pathway enrichment analysis of the differential metabolites. ResultsCompared with the control group， the model group showed reductions in the central activity time and central distance in the OFT （P<0.05）， the proportions of open-arm residence time and open-arm residence times in the EPM test （P<0.01）， and the proportions of open box activity time and open box activity distance in the LDB test （P<0.05）， which were increased in the medium- and high-dose MSNS groups compared with the model group （P<0.05）. Compared with the control group， the model group showed elevated levels of CRH， ACTH， and CORT in the serum （P<0.01）， and the elevations were diminished in the medium- and high-dose MSNS groups （P<0.05）. UPLC-MS results indicated that compared with the control group， the model group presented declined DA， GABA， 5-HIAA， 5-HT， and 5-HT/Trp levels （P<0.05， P<0.01） and raised Glu， NE， Kyn， and Kyn/Trp levels （P<0.05）. Compared with the model group， high-dose MSNS increased the GABA， 5-HIAA， and 5-HT/Trp levels （P<0.05） and lowered the Glu and Kyn/Trp levels （P<0.05）. Untargeted metabolomics identified that 16 CRS-induced metabolic disturbances were reversed by MSNS. KEGG pathway analysis indicated that MSNS primarily modulated eight core pathways including alanine/aspartate/glutamate metabolism， butyrate metabolism， arginine-proline metabolism， TCA cycle， unsaturated fatty acid biosynthesis， and tryptophan metabolism. The mechanisms involved multidimensional biological processes， including neurotransmitter homeostasis regulation， TCA cycle energy metabolism optimization， and inflammatory response suppression. ConclusionMSNS alleviates CRS-induced anxiety-like behaviors in mice by mitigating hypothalamic-pituitary-adrenal axis hyperactivity， improving hippocampal neurotransmitter and tryptophan metabolic pathways， and regulating alanine/aspartate/glutamate metabolism， butyrate metabolism， arginine-proline metabolism， and TCA cycle.