ObjectiveTo investigate the mechanism by which Xiebai San regulates respiratory tract and intestinal mucosal immunity in rats with allergic asthma. MethodsForty male SD rats were randomly divided into four groups based on body weight: control group, model group, positive control group, and Xiebai San group. The model group, positive control group, and Xiebai San group were sensitized with ovalbumin to establish a rat model of allergic asthma. From day 21 (the aerosol challenge phase), each group received daily gavage interventions simultaneously: the positive control group was administered dexamethasone (0.068 mg/kg), the Xiebai San group received Xiebai San solution (2 g/mL, 11.3 mL/kg), while the control and model groups were given an equal volume of normal saline, once daily for 14 consecutive days. After euthanasia, lung and intestinal tissues were collected. Hematoxylin and eosin staining was used to observe histopathological changes. Transmission electron microscopy was employed to examine tissue ultrastructure. Immunohistochemistry was applied to detect the positive reaction areas of phosphatidyl-inositol 3-kinase (PI3K) and protein kinase B (Akt) proteins. Total protein and total RNA were extracted from lung and intestinal tissues, then the protein and mRNA expression levels of PI3K and Akt genes were detected by Western blotting and real-time quantitative PCR, respectively. ResultsHistopathological results showed alveolar emphysema accompanied by inflammatory cell infiltration, and intestinal mucosal injury with inflammatory cell infiltration in the model group as compared with the control group; the cellular structure of lung tissues was disrupted in the model group, with reduced organelles, while the ultrastructural lesions in the intestine were relatively mild. Compared with the model group, Xiebai San group exhibited milder pathological changes in lung tissues, with occasional alveolar wall damage and a small amount of inflammatory cell infiltration; the intestinal mucosal structure was improved, glands were arranged regularly, and pathological changes such as tissue loosening and inflammatory infiltration were alleviated; the cellular structure of lung tissues was relatively intact with reduced severity of lesions, and no ultrastructural pathological changes were observed in intestinal tissues. Immunohistochemistry and Western blotting results showed that compared with the control group, the specific positive reaction areas of PI3K and Akt in lung and intestinal tissues were significantly increased in the model group (all P<0.001); meanwhile, the protein expression levels of PI3K and Akt were significantly upregulated (all P<0.05). Compared with the model group, the positive area of Akt protein in lung tissue was significantly reduced in the Xiebai San group (P<0.001), and the positive area of PI3K in intestinal tissue was also significantly decreased (P<0.000 1). Additionally, the protein expression levels of PI3K and Akt in lung and intestinal tissues were significantly downregulated (all P<0.01). Real-time quantitative PCR results showed that compared with the control group, the mRNA expression levels of PI3K and Akt genes in lung and intestinal tissues were significantly elevated in the model group (all P<0.05). Compared with the model group, the mRNA expression levels of PI3K and Akt genes in lung and intestinal tissues were significantly reduced in the Xiebai San group (all P<0.05). ConclusionXiebai San exerts protective effects on rats with allergic asthma by inhibiting the expression of key nucleic acids and proteins in the PI3K-Akt signaling pathway in lung and intestinal tissues, improving the morphological structure of lung tissue, and maintaining intestinal mucosal integrity, and regulating intestinal mucosal immune function.

ObjectiveTo construct and validate a clinical prediction model for inflammatory remission outcomes in rheumatoid arthritis （RA） patients with liver and kidney deficiency syndrome treated with Bushen Zhiwang Decoction （补肾治尪汤， BZD） based on metabolomics. MethodsA prospective cohort study was conducted， enrol-ling 60 RA patients with liver and kidney deficiency syndrome. All patients were treated with BZD and conventional-dose oral conventional synthetic disease-modifying antirheumatic drugs （csDMARDs） for 12 months. Clinical data were collected， and the change in disease activity score in 28 joints （DAS28） after treatment compared with baseline （△DAS28） was used as the primary outcome and grouping criterion. Peripheral blood samples were collected before treatment to analyze plasma metabolites. Differential analysis and least absolute shrinkage and selection operator （LASSO） regression were used to preliminarily screen differential metabolites， followed by machine learning algorithms to further identify a core metabolite combination. Based on the expression levels of the core metabolite combination， a novel metabolite index， namely the metabolomics-based inflammatory remission score （Met-IRS）， was calculated using standar-dized metabolite values， and its clinical applicability was evaluated. A clinical prediction model was constructed by integrating clinical characteristics and Met-IRS， and the model performance was assessed. ResultsAmong the 60 patients， those with △DAS28 ≥ 0.27 were assigned to the high inflammatory remission group， while those with △DAS28 ＜ 0.27 were assigned to the low inflammatory remission group， with 30 cases in each group. Compared to the low inflammatory remission group， the high inflammatory remission group showed a higher frequency of methotrexate use and a lower positive rate of rheumatoid factor （RF） （P＜0.05）. Seven core metabolites were identified as the optimal combination， including mangiferic acid， fatty acid-hydroxy fatty acid ester 40∶6， fatty acid-hydroxy fatty acid ester 18∶0， fatty acid-hydroxy fatty acid ester 36∶1， glucosylceramide， lysophosphatidylcholine 22∶5， and pregnanetriol ketone. The calculated Met-IRS comprehensively reflected the characteristics of differential metabolites and demonstrated clinical applicability. Met-IRS was significantly higher in the high inflammatory remission group than in the low inflammatory remission group， and was positively correlated with high inflammatory remission outcomes （P＜0.05）. Based on the variables Met-IRS， methotrexate use， leflunomide use， and RF positivity， a clinical prediction model for inflammatory remission in RA treatment （Cj-RTRM） was constructed. Model performance evaluation demonstrated that the model had good clinical predictive ability， with an area under the receiver operating characteristic curve （AUC） of 0.880， sensitivity 0.967， specificity 0.700 and Youden's index 0.667. ConclusionThe clinical prediction model Cj-RTRM constructed based on the metabolomics-based inflammatory remission score Met-IRS can effectively predict clinical inflammatory remission outcomes in RA patients treated with BZD and accurately identify the advantageous population for this treatment. This model provides guiding evidence for dynamic inflammation monitoring， targeted management， and identification of populations with advantages in traditional Chinese medicine.

Objective:To investigate the effect and mechanism of Jiedu Xiaoying Patch in rats with Hashimoto's thyroiditis (HT).Methods:Totally 32 rats were randomly divided into a blank group of 8 rats and a model group of 24 rats. The HT rat model was prepared by freely drinking 0.064% sodium iodide solution in the modeling module. 24 successfully modeled rats were randomly divided into model group, selenium yeast group, and patch group, with 8 rats in each group. Starting from the 9th week, the application group applied Jiedu Xiaoying Patch to the surface projection area of the thyroid gland in the neck of rats for 6 hours, once a day, for a total of 6 weeks; the selenium yeast group was orally administered with 21 μg/ml selenium yeast solution at a dose of 0.5 ml/100 g, while the blank group, model group, and patch group were orally administered with equal volumes of physiological saline solution once a day for a total of 6 weeks. The levels of TGAb,TPOAb, Sema 5A, and IL-17A in rat serum were detected by ELISA. The changes of thyroid tissue was observed with HE staining. The relative expression levels of plexin-A1 and plexin-B3 were determined through RT-PCR.Results:Compared with the model group, the levels of TPOAb, TGAb, Sema 5A, and IL-17A decreased ( P<0.05), and the expressions of plexin-A1 and plexin-B3 decreased in the selenium yeast group and the patch group ( P<0.05). The thyroid follicles in the model group were severely damaged, with a large number of lymphocytes infiltrating the interstices; the thyroid follicular structure of the selenium yeast group was relatively intact, and lymphocyte infiltration was reduced compared to the model group. The thyroid follicular structure of the patch group was basically intact, with a small amount of lymphocyte infiltration observed. Conclusion:Jiedu Xiaoying Patch can significantly reduce the levels of TPOAb and TGAb in HT rats. The mechanism may be related to reducing the content of Sema 5A, inhibiting the expressions of receptors plexin-A1 and plexin-B3, reducing the production of inflammatory cytokines such as IL-17A, and inhibiting immune and inflammatory responses.

Objective To observe the clinical efficacy of Huangqi Danggui Compound Decoction(mainly composed of Astragali Radix,Angelicae Sinensis Radix,etc.)combined with Shi's Acupuncture Therapy in the treatment of postpartum low back pain due of qi and blood depletion type.Methods A total of 138 patients diagnosed with postpartum low back pain from March 2021 to February 2024 in the outpatient and inpatient departments of the Second Affiliated Hospital of Hebei University of Chinese Medicine were selected as the study subjects.The patients were randomly divided into an observation group and a control group using a random number table,with 69 cases in each group.The control group was treated with Ibuprofen Sustained-Release Capsules combined with Shi's Acupuncture Therapy,while the observation group was additionally treated with Astragalus and Angelica Compound Decoction on the basis of the control group's treatment.Both groups were treated for 4 weeks.After treatment,the clinical efficacy of the two groups was evaluated.The changes in Oswestry Disability Index(ODI)and Visual Analogue Scale(VAS)scores before and after treatment,as well as the SF-36 Quality of Life Scale scores,were observed.The changes in follicle-stimulating hormone(FSH),luteinizing hormone(LH),and estradiol(E2)levels were compared before and after treatment,and the safety and incidence of adverse reactions in the two groups were evaluated.Results(1)The total effective rate in the observation group was 92.75%(64/69),while it was 79.71%(55/69)in the control group.The efficacy of the observation group was superior to that of the control group,with a statistically significant difference(P＜0.05).(2)After treatment,the ODI and VAS scores of both groups were significantly improved(P＜0.05),and the observation group showed significantly better improvement in ODI and VAS scores compared to the control group,with a statistically significant difference(P＜0.05).(3)After treatment,the SF-36 Quality of Life Scale scores of both groups improved significantly(P＜0.05),and the observation group showed significantly better improvement in SF-36 scores compared to the control group,with a statistically significant difference(P＜0.05).(4)After treatment,the FSH,LH,and E2 levels in the observation group were significantly improved(P＜0.05),and the observation group showed significantly better improvement in FSH,LH,and E2 levels compared to the control group,with a statistically significant difference(P＜0.05).In the control group,the FSH,LH,and E2 levels improved slightly,but there was no statistically significant difference compared to before treatment(P＞0.05).(5)There was no statistically significant difference in the incidence of adverse reactions between the observation group and the control group(P＞0.05).Conclusion Huangqi Danggui Compound Decoction combined with Shi's Acupuncture Therapy in the treatment of postpartum low back pain due to qi and blood depletion can significantly alleviate pain symptoms,improve lumbar function,regulate sex hormone levels,and enhance the quality of life of patients,with significant efficacy and good safety.

Abstract Modern western medicine typically focuses on treating specific symptoms or diseases, and traditional Chinese medicine (TCM) emphasizes the interconnections of the body’s various systems under external environment and takes a holistic approach to preventing and treating diseases. Phenomics was initially introduced to the field of TCM in 2008 as a new discipline that studies the laws of integrated and dynamic changes of human clinical phenomes under the scope of the theories and practices of TCM based on phenomics. While TCM Phenomics 1.0 has initially established a clinical phenomic system centered on Zhenghou (a TCM definition of clinical phenome), bottlenecks remain in data standardization, mechanistic interpretation, and precision intervention. Here, we systematically elaborates on the theoretical foundations, technical pathways, and future challenges of integrating digital medicine with TCM phenomics under the framework of “TCM phenomics 2.0”, which is supported by digital medicine technologies such as artificial intelligence, wearable devices, medical digital twins, and multi-omics integration. This framework aims to construct a closed-loop system of “Zhenghou–Phenome–Mechanism–Intervention” and to enable the digitization, standardization, and precision of disease diagnosis and treatment. The integration of digital medicine and TCM phenomics not only promotes the modernization and scientific transformation of TCM theory and practice but also offers new paradigms for precision medicine. In practice, digital tools facilitate multi-source clinical data acquisition and standardization, while AI and big data algorithms help reveal the correlations between clinical Zhenghou phenomes and molecular mechanisms, thereby improving scientific rigor in diagnosis, efficacy evaluation, and personalized intervention. Nevertheless, challenges persist, including data quality and standardization issues, shortage of interdisciplinary talents, and insufficiency of ethical and legal regulations. Future development requires establishing national data-sharing platforms, strengthening international collaboration, fostering interdisciplinary professionals, and improving ethical and legal frameworks. Ultimately, this approach seeks to build a new disease identification and classification system centered on phenomes and to achieve the inheritance, innovation, and modernization of TCM diagnostic and therapeutic patterns.

Objective:To design and evaluate a cell membrane vaccine strategy based on dendritic cell membrane microbubbles(DCM@MBs),and to explore its potential application in tumor immunotherapy,especially the immune-specific killing of tumor cells through the activation of T cells.Methods:At first,tumor cell membrane proteins were extracted and dendritic cells(DCs)were acti-vated to confirm that tumor antigens could effectively stimulate the maturation of immature DCs.Mature DC membranes were then mixed with lipids to prepare DCM@MBs,which were characterized for morphology,size,and protein composition by confocal laser scanning microscopy and sodium dodecyl sulfate-polyacrylamide gel electrophoresis.Finally,in vitro co-culture experiments were con-ducted to assess the effect of DCM@MBs on the activation of T cells and their ability for specific killing of tumor cells.Results:In the in vitro DC activation experiment,after stimulation with tumor cell membrane proteins,the 25 μg/mL group had a significant increase in the expression level of MHC class Ⅱ molecule(25.167%±1.203%)on the surface of immature DCs compared with the control group(P<0.001),and DCM@MBs presented with microbubbles encapsulated by red cell membranes,with uniform dispersion and a size of 1-5 μm.In the in vitro co-culture experiment,the amount of breast cancer cells(9.893±0.341)%.Conclusion:The DCM@MBs strategy proposed in this study shows significant potential in tu-mor immunotherapy and can effectively activate T cells and specifically kill and eliminate tumor cells,which provides new ideas for tu-mor immunotherapy.

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*

Antibody-drug conjugates (ADCs) represent a promising class of targeted cancer therapeutics that combine the specificity of monoclonal antibodies with the potency of cytotoxic payloads. Despite their therapeutic potential, the use of ADCs faces significant challenges, including off/on-target toxicity and resistance development. This review examines the current landscape of ADC development, focusing on the critical aspects of target selection and antibody engineering. We discuss strategies to increase ADC efficacy and safety, including multitarget approaches, pH-dependent antibodies, and masked peptide technologies. The importance of comprehensive antigen expression profiling in both tumor and normal tissues is emphasized, highlighting the role of advanced technologies, such as single-cell sequencing and artificial intelligence, in optimizing target selection. Furthermore, we explore combination therapies and innovations in linker‒payload chemistry, which may provide approaches for expanding the therapeutic window of ADCs. These advances pave the way for the development of more precise and effective cancer treatments, potentially extending ADC applications beyond oncology.
Humans ; Immunoconjugates/adverse effects* ; Neoplasms/immunology* ; Animals ; Antibodies, Monoclonal/therapeutic use* ; Antineoplastic Agents/therapeutic use*

OBJECTIVE: To review the research progress on the lower limb biomechanical characteristics of patients with discoid lateral meniscus (DLM) injury after surgery. METHODS: By searching relevant domestic and international research literature on DLM, the postoperative characteristics of knee joint movement biomechanics, tibiofemoral joint stress distribution, lower extremity force line, and patellofemoral joint changes in patients with DLM injury were summarized. RESULTS: Surgical treatment can lead to varying degrees of changes in the lower limb biomechanical characteristics of patients with DLM injury. Specifically, the kinematic biomechanics of the knee joint can significantly improve, but there are still problems such as extension deficits in the affected knee joint. The peak stress of the tibiofemoral joint decreases with the increase of the residual meniscus volume, and the degree of change is closely related to the residual meniscus volume. Preserving a larger volume of the meniscus, especially the anterior horn volume, helps to reduce stress concentration. The lower extremity force line will deviate outward after surgery, and the more meniscus is removed during surgery, the greater the change in the lower extremity force line after surgery. There are conditions such as cartilage degeneration, position and angle changes in the patellofemoral joint after surgery. CONCLUSION The changes in the lower limb biomechanical characteristics after DLM injury are closely related to the choice of surgical methods and rehabilitation programs. However, the mechanisms of biomechanical changes in multiple lower limb joints and individual differences still need to be further studied and clarified.
Humans ; Biomechanical Phenomena ; Tibial Meniscus Injuries/physiopathology* ; Menisci, Tibial/physiopathology* ; Knee Joint/surgery* ; Lower Extremity/physiopathology* ; Patellofemoral Joint/physiopathology* ; Range of Motion, Articular ; Knee Injuries/physiopathology*

OBJECTIVE: To compare the aesthetic effects of anterior maxilla clockwise rotation combined with segmental Le Fort Ⅰ osteotomy and whole maxilla clockwise rotation on improving paranasal concavity in patients with Class Ⅲ maxillofacial deformity. METHODS: A non-randomized controlled trial was designed, and 21 patients diagnosed with skeletal Class Ⅲ maxillofacial deformity were included. In the study, 11 patients in the test group were treated by segmental Le Fort Ⅰ osteotomy combined with anterior maxilla clockwise rotation, and 10 patients in the control group were treated by whole maxilla clockwise rotation. The CBCT and 3D photography of preoperative (T0), 2 weeks postoperative (T1), and 6 months postoperative (T2) were collected respectively, and the three-dimensional cephalometry was carried out. The differences of specific parameters between the two groups were compared by independent sample t-test, including saggital displacement of the cheek mass point (CK) and subalare point (SA), nasolabial angle, occlusal plane angle and labial inclination angle of the upper incisor. RESULTS: There were no significant differences of the parameters on T0 between the two groups. The average sagittal displacement of the upper incisors of the test group was (-0.71±1.67) mm and smaller than that of control group [(2.26±1.68) mm], t=-4.052, P < 0.05. The average angle of the occlusal plane clockwise rotation of the test group was 1.46°±2.38° and smaller than that of the control group (4.31°±1.83°), t=-3.047, P < 0.05. The angle of anterior maxilla clockwise rotation was 11.73°±2.81° during the surgery. The average saggital displacement of the paranasal soft tissue landmarks of the test group from T0 to T2 was larger than that of the control group [CK point, (4.96±1.18) mm vs. (2.01± 1.50) mm, P < 0.05;SA point, (5.19±1.17) mm vs. (2.69±1.45) mm, P < 0.05]. The labial inclination angle of the upper incisor of the test group was 112.15°±5.40° in T2 and significantly smaller than that of the control group (122.38°±8.83°), t=-3.237, P < 0.05. The nasolabial angle of the test group was 106.54°±12.82° in T2 and significantly larger than that of the control group (93.90°±12.46°), t=2.288, P < 0.05. CONCLUSION Compared with whole maxilla clockwise rotation, anterior maxilla clockwise rotation combined with segmental Le Fort Ⅰ osteotomy can increase the saggital displacement of the paranasal soft tissue, correct labial inclination of the upper incisors and the acute naso-labial angle and better improve the paranasal aesthetic defects in patients with Class Ⅲ maxillofacial deformity with less changing on the saggital orientation of the upper incisors and the occlusal plane angle.
Humans ; Maxilla/surgery* ; Female ; Male ; Osteotomy, Le Fort/methods* ; Malocclusion, Angle Class III/surgery* ; Adult ; Cephalometry ; Young Adult ; Rotation ; Adolescent