Pulmonary sarcoidosis is an immune system disease with an unclear etiology. Guided by the yang-reinforcing method， it is believed that the fundamental pathogenesis of pulmonary sarcoidosis lies in the disharmony between water and fire and the reckless movement of the ministerial fire. The failure of the spleen and stomach to maintain warmth， leading to the production of phlegm and blood stasis， is an important pathogenesis. The invasion of external pathogenic toxins， deeply penetrating into the interior， is considered a triggering factor for the disease. The treatment focuses on supplementing the yang， consolidating the kidney， drawing fire back to its source， warming the yang， benefiting the kidney， and nourishing the spleen to generate metal. It also emphasizes unblocking the yang， transforming turbidity， and eliminating phlegm and blood stasis.

ObjectiveTo explore the role and potential mechanism of circulating glutamate in enhancing insulin sensitivity by aerobic exercise. This research may provide a novel strategy for preventing metabolic diseases through precise exercise interventions. MethodsTo investigate the effects of elevated circulating glutamate on insulin sensitivity and its potential mechanisms, 18 male C57BL/6 mice aged 6 to 8 weeks were randomly divided into 3 groups: a control group (C), a group receiving 500 mg/kg glutamate supplementation (M), and a group receiving 1 000 mg/kg glutamate supplementation (H). The intervention lasted for 12 weeks, with treatments administered 6 d per week. Following the intervention, an insulin tolerance test (ITT) and a glucose tolerance test (GTT) were conducted. Circulating glutamate levels were measured using a commercial kit, and the activity of the skeletal muscle InsR/IRS1/PI3K/AKT signaling pathway was analyzed via Western blot. To further investigate the role of circulating glutamate in enhancing insulin sensitivity through aerobic exercise, 30 male C57BL/6 mice were randomly assigned to 3 groups: a control group (CS), an exercise intervention group (ES), and an exercise combined with glutamate supplementation group (EG). The ES group underwent treadmill-based aerobic exercise, while the EG group received glutamate supplementation at a dosage of 1 000 mg/kg in addition to aerobic exercise. The intervention lasted for 10 weeks, with sessions occurring 6 d per week, and the same procedures were followed afterward. To further elucidate the mechanism by which glutamate modulates the InsR/IRS1/PI3K/AKT signaling pathway, C2C12 myotubes were initially subjected to graded glutamate treatment (0, 0.5, 1, 3, 5, 10 mmol/L) to determine the optimal concentration for cellular intervention. Subsequently, the cells were divided into 3 groups: a control group (C), a glutamate intervention group (G), and a glutamate combined with MK801 (an NMDA receptor antagonist) intervention group (GK). The G group was treated with 5 mmol/L glutamate, while the GK group received 50 μmol/L MK801 in addition to 5 mmol/L glutamate. After 24 h of intervention, the activity of the InsR/IRS1/PI3K/AKT signaling pathway was analyzed using Western blot. ResultsCompared to the mice in group C, the circulating glutamate levels, the area under curve (AUC) of ITT, and the AUC of GTT in the mice of group H were significantly increased. Additionally, the expression levels of p-InsRβ, IRS1, p-AKT, and p-mTOR proteins in skeletal muscle were significantly downregulated. Compared to the mice in group CS, the circulating glutamate levels, the AUC of ITT, and the AUC of GTT in the mice of group ES were significantly reduced. Additionally, the expression levels of p-InsRβ, IRS1, p-AKT, and p-mTOR proteins in skeletal muscle of group ES mice were significantly upregulated. There were no significant changes observed in the mice of group EG. Compared to the cells in group 0 mmol/L, the expression levels of p-InsRβ, p-IRS1, p-PI3K, and p-AKT proteins in cells of group 5 mmol/L were significantly downregulated. Compared to the cells in group C, the expression levels of p-InsRβ, p-IRS1, p-PI3K, and p-AKT proteins in the cells of group G were significantly downregulated. No significant changes were observed in the cells of group GK. ConclusionLong-term aerobic exercise can improve insulin sensitivity by lowering circulating levels of glutamate. This effect may be associated with the upregulation of the InsR/IRS1/AKT signaling pathway activity in skeletal muscle. Furthermore, glutamate can weaken the activity of the InsR/IRS1/PI3K/AKT signaling pathway in skeletal muscle, potentially by binding to NMDAR expressed in skeletal muscle.

Asthma is a chronic inflammatory disease involving multiple inflammatory cells and cytokines. Its pathogenesis is complex, involving various cells and cytokines. Traditional Chinese medicine(TCM) theory suggests that the pathogenesis of asthma is closely related to the dysfunction of internal organs such as the lungs, spleen, and kidneys. In contrast, modern immunological studies have revealed the central role of T helper 1(Th1)/T helper 2(Th2) and T helper 17(Th17)/regulatory T(Treg) cellular immune imbalance in the pathogenesis of asthma. Th1/Th2 imbalance is manifested as hyperfunction of Th2 cells, which promotes the synthesis of immunoglobulin E(IgE) and the activation of eosinophil granulocytes, leading to airway hyperresponsiveness and inflammation.Meanwhile, Th17/Treg imbalance exacerbates the inflammatory response in the airways, further contributing to asthma pathology.Currently, therapeutic strategies for asthma are actively exploring potential targets for regulating the balance of Th1/Th2 and Th17/Treg immune responses. These targets include cytokines, transcription factors, key proteins, and non-coding RNAs. Precisely regulating the expression and function of these targets can effectively modulate the activation and differentiation of immune cells. In recent years,traditional Chinese medicine active ingredients have shown unique potential and prospects in the field of asthma treatment. Based on this, the present study systematically summarizes the efficacy and specific mechanisms of TCM active ingredients in treating asthma by regulating Th1/Th2 and Th17/Treg immune balance through literature review and analysis. These active ingredients, including flavonoids, terpenoids, polysaccharides, alkaloids, and phenolic acids, exert their effects through various mechanisms, such as inhibiting the activation of inflammatory cells, reducing the release of cytokines, and promoting the normal differentiation of immune cells. This study aims to provide a solid foundation for the widespread application and in-depth development of TCM in asthma treatment and to offer new ideas for clinical research and drug development of asthma.
Asthma/genetics* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Th2 Cells/drug effects* ; Th17 Cells/drug effects* ; T-Lymphocytes, Regulatory/drug effects* ; Th1 Cells/drug effects* ; Animals ; Cytokines/immunology* ; Medicine, Chinese Traditional

Asthma, a chronic inflammatory airway disease with a high global prevalence, has a complex pathogenesis, in which airway remodeling plays a key role in the chronicity of the disease. Airway remodeling involves a series of pathophysiological changes, including airway epithelial damage, proliferation of mucous glands and goblet cells, subepithelial fibrosis, proliferation and migration of airway smooth muscle cells, and epithelial-mesenchymal transition. These complex pathological changes significantly increase airway resistance and responsiveness, forming an important pathological basis for refractory asthma. Currently, the regulatory mechanisms of airway remodeling focus on signaling pathways and regulatory targets. The signaling pathways include phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), nuclear factor-κB(NF-κB), transforming growth factor-β1(TGF-β1)/Smads, and mitogen-activated protein kinase(MAPK). The regulatory targets include microRNAs(miRNAs), competing endogenous RNAs(ceRNAs), long non-coding RNAs(lncRNAs), and circular RNAs(circRNAs). Key proteins involved in these processes include TGF-β1, silencing information regulator 2-related enzyme 1(SIRT1), chitinase 3-like protein 1(YKL-40), and adenosine deaminase-metalloproteinase 33(ADAM33). In recent years, the potential of traditional Chinese medicine in the treatment of asthma has become increasingly evident. Its active ingredients, extracts, and complexes can inhibit airway remodeling in asthma through multiple pathways, demonstrating a variety of effects, including anti-inflammatory actions, inhibition of smooth muscle cell proliferation and migration, regulation of epithelial-mesenchymal transition, attenuation of fibrosis and basement membrane thickening, reduction of mucus secretion, inhibition of vascular remodeling, modulation of immune imbalance, and antioxidative stress. This paper aims to provide an in-depth analysis of the pathogenesis and therapeutic targets of asthma, offering theoretical support and innovative strategies for clinical research and drug development in the treatment of asthma.
Asthma/pathology* ; Humans ; Airway Remodeling/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Animals ; Signal Transduction/drug effects* ; Medicine, Chinese Traditional ; Transforming Growth Factor beta1/metabolism*

A variety of chromatographic techniques, including silica gel, ODS, Sephadex LH-20, and HPLC, were employed to isolate and purify the fermentation products of rice with Monascus sanguineus. A total of 38 compounds were isolated, and their structures were identified by UV, IR, NMR, MS, calculated ECD, and comparison with literature data. Compounds 1-4 were identified as new natural products, and other compounds were isolated from this fungus for the first time. A RAW264.7 macrophage model of lipopolysaccharide(LPS)-induced inflammation was used to evaluate the anti-inflammatory activities of all the compounds. The results showed that compound 6 exhibited a certain inhibitory effect on the production of nitric oxide in LPS-induced RAW264.7 cells, with an inhibition rate of 53.08%.
Monascus/chemistry* ; Mice ; Animals ; Anti-Inflammatory Agents/isolation & purification* ; RAW 264.7 Cells ; Macrophages/immunology* ; Nitric Oxide/immunology* ; Oryza/metabolism* ; Fermentation

OBJECTIVES: To develop a scale for evaluating responsive feeding behaviors among caregivers of children aged 0-24 months in China, and to examine its reliability and validity. METHODS: An initial item pool was constructed through literature review, expert panel discussions, and caregiver interviews. Items were screened and revised using expert consultation and item analysis. A total of 523 caregivers of children aged 0-24 months were randomly selected from urban community health service centers in Nanjing for a formal survey to assess the scale's reliability and validity. RESULTS: The scale comprised two age-specific subscales: 0-6 months (4 dimensions, 18 items) and 7-24 months (5 dimensions, 29 items). Cronbach's alpha values for the two subscales were 0.766 and 0.850, respectively; split-half reliability coefficients were 0.616 and 0.716. Content validity indices were 0.83 for the 0-6 months subscale and 0.86 for the 7-24 months subscale. Confirmatory factor analysis supported the structural validity of both subscales, with all fit indices within acceptable ranges. CONCLUSIONS The two age-specific subscales demonstrate good reliability and validity and can serve as practical tools for assessing caregivers' responsive feeding behaviors in children aged 0-24 months, suitable for clinical application and dissemination.
Humans ; Infant ; Caregivers/psychology* ; Male ; Female ; Feeding Behavior ; Child, Preschool ; Infant, Newborn ; Reproducibility of Results

OBJECTIVE: To investigate the effects of wheat-grain moxibustion at the Guanyuan point on testosterone (T) synthesis and the hypothalamic-pituitary-gonadal (HPG) axis in naturally aged mice. METHODS: We fed 40 twelve-month-old SPF male C57BL/6J mice with a normal diet for 3 months, randomized them into a moxibustion and an aged group of an equal number, and selected 7 four-month-old ones as young controls. We treated the animals of the moxibustion group by wheat-grain moxibustion at the Guanyuan point, once 5 moxibustion sticks, qd, 5 times a week, and fed those of the aged group normally, all for 12 weeks. After treatment, we obtained the testicular index of the mice, observed the histomorphology of the testis tissue by HE staining, measured the contents of T in the testis, gonadotropin-releasing hormone (GnRH) in the hypothalamus and total T (tT), free T (fT), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the serum by ELISA, and determined the expressions of silence information regulator-1 (SIRT1), P53, glutathione peroxidase (GPX4) and cholesterol side-chain?cleavage enzyme (CYP11A1) in the testis by Western blot. RESULTS: Compared with the young controls, the mice in the aged group showed obviously losing and dull hair, energy declination, loose structure of the spermatogenic tubule with different degrees of cell loss and rupture, reduced testicular index, and evident aging phenotype. In comparison with the aged mice, the animals of the moxibustion group were fairly energetic and exhibited distinct structure of the spermatogenic tubules, orderly arranged and highly differentiated cells at all levels, significantly increased T level, up-regulated expressions of SIRT1, GPX4 and CYP11A1, and down-regulated expression of P53 in testis tissue, and elevated levels of GnRH, FSH, LH, tT and fT in the HPG axis. CONCLUSION Wheat-grain moxibustion at the Guanyuan point protects testosterone synthesis in the testis tissue of naturally aged mice, promotes negative feedback regulation of the HPG axis, and improves low testosterone.
Animals ; Male ; Moxibustion ; Mice ; Testosterone/metabolism* ; Mice, Inbred C57BL ; Testis/metabolism* ; Hypothalamo-Hypophyseal System/metabolism* ; Triticum ; Gonadotropin-Releasing Hormone/metabolism* ; Luteinizing Hormone/blood* ; Follicle Stimulating Hormone/blood* ; Aging ; Hypothalamus/metabolism* ; Acupuncture Points ; Sirtuin 1/metabolism* ; Hypothalamic-Pituitary-Gonadal Axis

Attempts have been made to modulate motor sequence learning (MSL) through repetitive transcranial magnetic stimulation, targeting different sites within the sensorimotor network. However, the target with the optimum modulatory effect on neural plasticity associated with MSL remains unclarified. This study was therefore designed to compare the role of the left primary motor cortex and the left supplementary motor area proper (SMAp) in modulating MSL across different complexity levels and for both hands, as well as the associated neuroplasticity by applying intermittent theta burst stimulation together with the electroencephalogram and concurrent transcranial magnetic stimulation. Our data demonstrated the role of SMAp stimulation in modulating neural communication to support MSL, which is achieved by facilitating regional activation and orchestrating neural coupling across distributed brain regions, particularly in interhemispheric connections. These findings may have important clinical implications, particularly for motor rehabilitation in populations such as post-stroke patients.
Humans ; Transcranial Magnetic Stimulation ; Motor Cortex/physiology* ; Male ; Electroencephalography ; Neuronal Plasticity/physiology* ; Female ; Adult ; Evoked Potentials, Motor/physiology* ; Young Adult ; Learning/physiology*

The angiogenic response is essential for the repair of ischemic brain tissue. Integrin α6 (Itga6) expression has been shown to increase under hypoxic conditions and is expressed exclusively in vascular structures; however, its role in post-ischemic angiogenesis remains poorly understood. In this study, we demonstrate that mice with endothelial cell-specific knockout of Itga6 exhibit reduced neovascularization, reduced pericyte coverage on microvessels, and accelerated breakdown of microvascular integrity in the peri-infarct area. In vitro, endothelial cells with ITGA6 knockdown display reduced proliferation, migration, and tube-formation. Mechanistically, we demonstrated that ITGA6 regulates post-stroke angiogenesis through the PI3K/Akt-eNOS-VEGFA axis. Importantly, the specific overexpression of Itga6 in endothelial cells significantly enhanced neovascularization and enhanced the integrity of microvessels, leading to improved functional recovery. Our results suggest that endothelial cell Itga6 plays a crucial role in key steps of post-stroke angiogenesis, and may represent a promising therapeutic target for promoting recovery after stroke.
Animals ; Nitric Oxide Synthase Type III/metabolism* ; Mice ; Proto-Oncogene Proteins c-akt/metabolism* ; Integrin alpha6/genetics* ; Endothelial Cells/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Stroke/pathology* ; Vascular Remodeling/physiology* ; Vascular Endothelial Growth Factor A/metabolism* ; Mice, Knockout ; Signal Transduction/physiology* ; Mice, Inbred C57BL ; Male ; Neovascularization, Physiologic/physiology*

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*