Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

ObjectiveTo explore the role of the histone deacetylase Sirtuin-1 （SIRT1）/p53 signaling pathway in promoting apoptosis of non-small cell lung cancer cells （NSCLC） induced by the co-stimulatory molecule B7 homolog 3 （B7-H3）. MethodsThe GEPIA 2 platform was used for survival analysis of NSCLC patients based on B7⁃H3 gene expression levels. The Gene Enrichment Analysis （GSEA） method was used to analyze the enrichment characteristics of B7⁃H3 molecules in the gene set of cell apoptosis. In the non-small cell lung cancer A549 cell line， B7⁃H3 was knocked down， and the protein expression levels of SIRT1 and p53 were detected by Western blot. B7⁃H3 was overexpressed in A549 cells and the apoptosis rate was analyzed by flow cytometry after Annexin V/PI double staining. Overexpression of B7⁃H3 and knockdown of SIRT1 were performed in A549 cell line. The expression levels of p53 and apoptosis-related proteins B-cell lymphoma/leukemia-2 （Bcl-2） and Bcl-2-associated X protein （Bax） were detected respectively by Western blot. Cell apoptosis rate was analyzed by flow cytometry after Annexin V/PI double staining. ResultsThe overall survival of the B7-H3 high-expression group was significantly lower than that of the low-expression group （P<0.01）. B7-H3 was significantly enriched in the cell apoptosis signaling pathway and the p53 signaling pathway （P<0.05）. Compared with the control group， the expression of SIRT1 was significantly downregulated， and p53 was significantly upregulated in the B7⁃H3 knockdown group （both P<0.001）. Overexpression of B7-H3 significantly up-regulated SIRT1 protein expression （P<0.05）， down-regulated p53 expression （P<0.01）， and markedly increased the Bcl-2/Bax ratio of apoptosis-related proteins （P<0.001）. The results of Annexin V/PI double staining showed that the apoptosis rate of A549 cells with overexpressed B7⁃H3 decreased （the apoptosis rate of the control group was 26.72%±4.13%， while that of the B7⁃H3 overexpression group was 13.87%±0.82%； P<0.01）. In B7-H3-overexpressing cell lines， SIRT1 knockdown significantly reversed apoptosis （P<0.05）， up-regulated p53 protein expression （P<0.001）， and markedly reduced the Bcl-2/Bax ratio （P<0.001）. ConclusionB7-H3 molecule inhibits the apoptosis of non-small cell lung cancer cells via the SIRT1/p53 signaling pathway.

ObjectiveThe Golgi apparatus serves as a central hub in the eukaryotic secretory pathway, responsible for the processing, sorting, and trafficking of proteins and lipids. In mammalian cells, the Golgi typically forms a perinuclear ribbon-like structure composed of laterally connected cisternae stacks.The maintenance of Golgi ribbon structure depends on the balance of membrane flux across multiple intracellular trafficking pathways, yet the specific contributions of distinct trafficking branches to Golgi macroscopic morphology remain elusive. In mammalian cells, the Golgi ribbon is typically organized as a perinuclear, laterally connected structure composed of stacked cisternae, and its integrity is highly dynamic and sensitive to perturbations in membrane trafficking. This study aims to elucidate the role of coat protein complex I (COPI)-mediated retrograde transport in maintaining the Golgi ribbon and to dissect the functional relationship between the transmembrane cargo receptors LEPROT/LEPROTL1 (LEPROTs) and the COPI adaptor GOLPH3. MethodsUsing siRNA interference and gene-deficient cell lines, we selectively perturbed COPI- or adaptor protein complex 1 (AP-1)-mediated trafficking pathways in HeLa cells. To quantitatively evaluate Golgi morphology, we employed a “Golgi Angle”-based measurement to assess its circumferential distribution around the nucleus. The spatial distribution of the Golgi ribbon was quantitatively analyzed using confocal microscopy, while Golgi ultrastructure and vesicle density were examined via transmission electron microscopy. Additionally, the subcellular distribution of COPI components was assessed by immunofluorescence co-localization. ResultsSelective inhibition of COPI retrograde transport significantly induced the circumferential extension of the Golgi ribbon around the nucleus, whereas blocking AP-1-mediated anterograde transport resulted in Golgi compaction, indicating opposing roles. These results suggest that different trafficking branches downstream of ARF1 exert distinct and even antagonistic effects on Golgi morphology. LEPROTs-deficient cells exhibited a Golgi extension phenotype highly consistent with COPI impairment. Furthermore, knockdown of GOLPH3 in a LEPROTs double-knockout background produced a significant additive effect on Golgi extension, suggesting that LEPROTs and GOLPH3 play non-redundant roles in regulating COPI-related trafficking processes. Mechanistically, loss of either LEPROTs or GOLPH3 led to the aberrant accumulation of COPI components at endoplasmic reticulum exit sites, accompanied by a reduction in COPI-like vesicles around the Golgi. This redistribution indicates a defect in COPI recycling between the ER-Golgi interface and the Golgi apparatus. Ultrastructural analysis revealed that Golgi cisternae in defective cells became shorter and thicker while maintaining a stable number of stacks. In parallel, the density of Golgi-associated vesicles was markedly decreased, further supporting an impairment in COPI vesicle formation or budding processes. ConclusionThis study demonstrates that active COPI retrograde transport is a critical factor in restricting the over-connection of the Golgi ribbon and maintaining its compactness. Rather than causing fragmentation, partial disruption of COPI function leads to a distinct morphological outcome characterized by Golgi ribbon extension at the light microscopy level and cisternal remodeling at the ultrastructural level. LEPROTs and GOLPH3 cooperatively promote the recycling and vesiculation of COPI components, thereby imposing a structural constraint on the Golgi periphery. Our findings support a model in which multiple adaptor proteins act in parallel to sustain efficient COPI cycling, thereby maintaining Golgi structural homeostasis. These findings provide new cell biological evidence for the membrane trafficking basis of Golgi morphological homeostasis.

OBJECTIVE To establish a quality control method for Jinbei oral liquid based on multi-wavelength switching high performance liquid chromatography （HPLC） fingerprint， chemical pattern recognition and multi-index content determination. METHODS A total of 15 batches of Jinbei oral liquid were used as test samples. The Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine （ Version 2012 ） was adopted to establish multi-wavelength switching HPLC fingerprints， followed by chromatographic peak identification and similarity evaluation. Cluster analysis， principal component analysis and orthogonal partial least squares-discriminant analysis were applied to conduct chemical pattern recognition on the 15 batches of samples. The multi-wavelength switching HPLC method was used to simultaneously determine the contents of neochlorogenic acid， chlorogenic acid， cryptochlorogenic acid， forsythoside A， baicalin， salvianoli c acid B and wogonoside in samples. RESULTS A total of 25 common peaks were calibrated in the fingerprints of 15 batches of Jinbei oral liquid， among which 7 common peaks were unambiguously identified. The similarity of all samples was higher than 0.960. Chemical pattern recognition results showed that samples S1-S8 were clustered into group 1， and samples S9-S15 were clustered into group 2. Baicalin， wogonoside， neochlorogenic acid， chlorogenic acid and salvianolic acid B were identified as the differential quality markers. The average contents of neochlorogenic acid， chlorogenic acid， cryptochlorogenic acid， forsythoside A， baicalin， salvianolic acid B and wogonoside in 15 batches of Jinbei oral liquid were 0.213 7， 0.085 3， 0.104 9， 0.287 3， 0.420 1， 0.062 1， 0.176 0 mg/mL， respectively. CONCLUSIONS The established quality control method for Jinbei oral liquid combining multi-wavelength switching HPLC fingerprint， chemical pattern recognition and multi-index content determination is stable and reliable， which can provide a reference for the formulation of quality standards of this preparation.

OBJECTIVE To establish a quality control method for Jinbei oral liquid based on multi-wavelength switching high performance liquid chromatography （HPLC） fingerprint， chemical pattern recognition and multi-index content determination. METHODS A total of 15 batches of Jinbei oral liquid were used as test samples. The Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine （ Version 2012 ） was adopted to establish multi-wavelength switching HPLC fingerprints， followed by chromatographic peak identification and similarity evaluation. Cluster analysis， principal component analysis and orthogonal partial least squares-discriminant analysis were applied to conduct chemical pattern recognition on the 15 batches of samples. The multi-wavelength switching HPLC method was used to simultaneously determine the contents of neochlorogenic acid， chlorogenic acid， cryptochlorogenic acid， forsythoside A， baicalin， salvianoli c acid B and wogonoside in samples. RESULTS A total of 25 common peaks were calibrated in the fingerprints of 15 batches of Jinbei oral liquid， among which 7 common peaks were unambiguously identified. The similarity of all samples was higher than 0.960. Chemical pattern recognition results showed that samples S1-S8 were clustered into group 1， and samples S9-S15 were clustered into group 2. Baicalin， wogonoside， neochlorogenic acid， chlorogenic acid and salvianolic acid B were identified as the differential quality markers. The average contents of neochlorogenic acid， chlorogenic acid， cryptochlorogenic acid， forsythoside A， baicalin， salvianolic acid B and wogonoside in 15 batches of Jinbei oral liquid were 0.213 7， 0.085 3， 0.104 9， 0.287 3， 0.420 1， 0.062 1， 0.176 0 mg/mL， respectively. CONCLUSIONS The established quality control method for Jinbei oral liquid combining multi-wavelength switching HPLC fingerprint， chemical pattern recognition and multi-index content determination is stable and reliable， which can provide a reference for the formulation of quality standards of this preparation.

"Spirit turns but does not reverse； if it reverses， it ceases to turn" originates from the Plain Questions： Discussion on Essential Jade Plates （《素问·玉版论要篇》）. It profoundly summarizes the objectivity of life as a phenomenon subject to the laws of the universe and nature， while also expressing the subjectivity of individuals possessing systematic， stable， and ordered biological rhythms. In light of relevant ancient philosophical insights， the theory of "spirit turns but does not reverse； if it reverses， it ceases to turn" embodies the principles of constant motion in life， change according to dao （道）， orderly progression， and the rule that reversal disrupts continuity. In clinical diagnosis and treatment， one should adopt the therapeutic principle of regulating spirit to promote "spirit turning". Guiding along the trend and acting in accordance with the natural momentum must be adopted to maintain the operation of spirit turning. Adhering to constancy while recognizing variability， and prioritizing harmony above all， should be employed to ensure the orderly progress of spirit turning. Regulating qi movement serves as the driving force behind facilitating spirit turning. This will provide clinical insights and theoretical foundations for treating diseases through the concept of "regulating spirit".

"Spirit turns but does not reverse； if it reverses， it ceases to turn" originates from the Plain Questions： Discussion on Essential Jade Plates （《素问·玉版论要篇》）. It profoundly summarizes the objectivity of life as a phenomenon subject to the laws of the universe and nature， while also expressing the subjectivity of individuals possessing systematic， stable， and ordered biological rhythms. In light of relevant ancient philosophical insights， the theory of "spirit turns but does not reverse； if it reverses， it ceases to turn" embodies the principles of constant motion in life， change according to dao （道）， orderly progression， and the rule that reversal disrupts continuity. In clinical diagnosis and treatment， one should adopt the therapeutic principle of regulating spirit to promote "spirit turning". Guiding along the trend and acting in accordance with the natural momentum must be adopted to maintain the operation of spirit turning. Adhering to constancy while recognizing variability， and prioritizing harmony above all， should be employed to ensure the orderly progress of spirit turning. Regulating qi movement serves as the driving force behind facilitating spirit turning. This will provide clinical insights and theoretical foundations for treating diseases through the concept of "regulating spirit".

OBJECTIVE To develop a risk screening scale for medication adherence in anticoagulated patients and evaluate its reliability and validity， thereby providing an assessment tool for identifying medication adherence risks during anticoagulant therapy and implementing individualized interventions.METHODS Based on the protection motivation theory， a preliminary scale containing 20 items was developed through literature analysis， semi-structured interviews， expert consultation and a pilot survey. Convenience sampling was used to distribute questionnaires to patients receiving anticoagulant therapy at multiple medical institutions. Item analysis was conducted to select items. Exploratory factor analysis （EFA） and confirmatory factor analysis （CFA） were used to assess construct validity and further screen items. The New General Self-Efficacy Scale-Short Form （NGSES-SF） was used to assess criterion-related validity， and the internal consistency and split-half reliability of the scale were evaluated.RESULTS A total of 425 questionnaires were distributed， and 411 valid questionnaires were recovered， yielding an effective recovery rate of 96.71%. The final scale consisted of four dimensions：perceived severity， perceived susceptibility， response efficacy and self-efficacy， with a total of 11 items. EFA extracted four common factors， with a cumulative variance contribution rate of 68.805%. CFA showed the Chi-square degrees of freedom ratio was 1.839， the root mean square error of approximation was 0.064， the goodness-of-fit index was 0.945， the comparative fit index was 0.979， and the Tucker-Lewis index was 0.969. The total score of the scale and the scores of each dimension were significantly positively correlated with the scores of the criterion scale NGSES-SF （ P ＜0.05）， and the correlation coefficient between the total score of the scale and the total score of NGSES-SF was 0.346. The Cronbach’s α coefficient for internal consistency was 0.878， and the split-half reliability coefficient was 0.743.CONCLUSIONS The medication adherence risk screening scale for patients on anticoagulant therapy constructed in this study demonstrated good reliability and validity， which can be used to screen for medication adherence risk in patients on anticoagulant therapy， and serve as an assessment tool for stratified targeted interventions in clinical practice.

This study aimed to investigate the underlying mechanisms of Duhuo Jisheng Decoction(DJD) in the prevention and treatment of knee osteoarthritis(KOA). Forty SPF New Zealand rabbits were randomly divided using SPSS 26.0 software into five groups: blank group, model group, low-dose DJD group, high-dose DJD group, and high-dose DJD+phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathway activator group(high-dose DJD+740Y-P group), with eight rabbits in each group. Except for the blank group, the KOA model was established in the other groups using papain injection into the knee joint cavity combined with forced flexion of the knee joint. The day after modeling, the blank group and model group were given normal saline at 10 mL·kg~(-1) by gavage, the low-dose DJD group received DJD at 8.8 g·kg~(-1) by gavage, the high-dose DJD group received DJD at 35.2 g·kg~(-1) by gavage, and the high-dose DJD+740Y-P group received DJD at 35.2 g·kg~(-1) by gavage along with 740Y-P at 0.15 μmoL·kg~(-1) injected via the auricular vein. All groups received treatment continuously for four weeks. After modeling and intervention, behavioral observations were performed for all groups, and after the intervention, imaging assessments of the knee joints were conducted. Cartilage from the knee joints was collected, and gross morphological changes were observed. Pathological changes in cartilage tissue were examined using hematoxylin-eosin(HE) staining. The results of these observations were quantitatively evaluated using the Lequesne MG score, Kellgren-Lawrence(K-L) grading, Pelletier score, and Mankin score. ELISA was used to measure the levels of interleukin-1β(IL-1β), interleukin-18(IL-18), and matrix metalloproteinase 13(MMP13) in cartilage tissue. Real-time RT-PCR was used to detect the mRNA expression levels of PI3K, Akt, mTOR, Nod-like receptor protein 3(NLRP3), cysteine protease 1(caspase-1), and gasdermin D(GSDMD) in cartilage tissue. Western blot was employed to measure the protein expression levels of PI3K, Akt, mTOR, NLRP3, caspase-1, and GSDMD. The results showed that compared with the blank group, the model group exhibited significant knee joint degeneration, increased Lequesne MG score, K-L grading, Pelletier score, and Mankin score, elevated levels of IL-1β, IL-18, and MMP13 in cartilage tissue, activation of PI3K, Akt, and mTOR phosphorylation along with increased mRNA expression levels, and elevated protein and mRNA expression levels of NLRP3, caspase-1, and GSDMD. Compared with the model group, these indicators were reversed in both the low-dose and high-dose DJD groups, with the high-dose group showing greater decline degree than the low-dose DJD group. However, compared with the high-dose DJD group, the improvements in knee joint degeneration were less pronounced in the high-dose DJD+740Y-P group, with increased Lequesne MG score, K-L grading, Pelletier score, Mankin score, elevated levels of IL-1β, IL-18, and MMP13, activation of PI3K, Akt, and mTOR phosphorylation along with increased mRNA expression, and increased protein and mRNA expression levels of NLRP3, caspase-1, and GSDMD. In conclusion, DJD is effective and safe in the treatment of KOA, and its mechanism may be related to the inhibition of PI3K/Akt/mTOR signaling pathway-mediated pyroptosis in cartilage tissue, thereby improving knee joint bone structure, reducing the inflammatory response, and preventing cartilage matrix degradation.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rabbits ; TOR Serine-Threonine Kinases/genetics* ; Osteoarthritis, Knee/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Signal Transduction/drug effects* ; Male ; Disease Models, Animal ; Pyroptosis/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Humans ; Female

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