BACKGROUND:Although researchers have noted that fibroblast growth factor receptor 1 shows great potential in rheumatoid arthritis bone destruction,there is a lack of reviews related to the potential mechanisms of fibroblast growth factor receptor 1 in rheumatoid arthritis bone destruction. OBJECTIVE:To comprehensively analyze the mechanism of fibroblast growth factor receptor 1 in bone destruction in rheumatoid arthritis by reviewing the relevant literature at both home and abroad. METHODS:We searched the CNKI database using the Chinese search terms"fibroblast growth factor receptor 1,rheumatoid arthritis,bone destruction,bone cells,osteoblasts,osteoclasts,chondrocytes,macrophages,synovial fibroblasts,T cells,vascular endothelial cells."PubMed database was searched using the English search terms"fibroblast growth factor receptor 1,rheumatoid arthritis,bone destruction,osteocytes,osteoblasts,osteoclasts,chondrocytes,macrophages,synovial fibroblasts,T cells,endothelial cells."The search period focused on April 1992 to January 2024.After screening the literature by reading titles,abstracts,and full texts,a total of 82 articles were finally included for review according to inclusion and exclusion criteria. RESULTS AND CONCLUSION:Fibroblast growth factor receptor 1 was found to be widely expressed in bone tissue-associated cells,including osteoblasts,osteoclasts,and osteoclasts.Fibroblast growth factor receptor 1 affects bone remodeling and homeostasis by regulating the function of these cells,as well as promoting the onset and progression of bone destruction in rheumatoid arthritis.Fibroblast growth factor receptor 1 is involved in the inflammatory response of synovial fibroblasts and macrophages and regulates angiogenesis of endothelial cells in synovial tissues.Fibroblast growth factor receptor 1 promotes bone destruction in several ways.Fibroblast growth factor receptor 1 may be a potential causative agent of bone destruction in rheumatoid arthritis and provides a reference for further research on its therapeutic targets.

The theory of "origin essence-origin qi-origin spirit" is rooted in the theory of "essence-qi-spirit", which explains that origin essence, origin qi, origin spirit as the important material foundation, energy power and regulation center in the process of growth and development of the organism, are mutual and complementary to each other, and operate orderly under the guidance of the ministerial fire. Tumor is essentially an abnormal disorder of the growth and development process of the organism, and its occurrence and development are directly related to the mutation of origin essence and the alienation of ministerial fire, and closely related to the attenuation of origin qi, the departure of ministerial fire, and the inefficiency of origin spirit, and the delusional movement of ministerial fire. Based on the theory of "origin essence-origin qi-origin spirit", the tumor can be treated in the clinic by regulating the ministerial fire suppressing origin essence to inhibit the tumor development, strengthening the spleen and benefiting the qi to slow down the attenuation of origin qi, and nourishing the heart and cultivating the mind to stabilize the power of origin spirit in order to further improve the understanding of TCM on the etiology of tumors, and at the same time, to provide a new direction and ideas for the clinical treatment of tumors.

Network pharmacology has gained widespread application in drug discovery, particularly in traditional Chinese medicine (TCM) research, which is characterized by its "multi-component, multi-target, and multi-pathway" nature. Through the integration of network biology, TCM network pharmacology enables systematic evaluation of therapeutic efficacy and detailed elucidation of action mechanisms, establishing a novel research paradigm for TCM modernization. The rapid advancement of machine learning, particularly revolutionary deep learning methods, has substantially enhanced artificial intelligence (AI) technology, offering significant potential to advance TCM network pharmacology research. This paper describes the methodology of TCM network pharmacology, encompassing ingredient identification, network construction, network analysis, and experimental validation. Furthermore, it summarizes key strategies for constructing various networks and analyzing constructed networks using AI methods. Finally, it addresses challenges and future directions regarding cell-cell communication (CCC)-based network construction, analysis, and validation, providing valuable insights for TCM network pharmacology.
Medicine, Chinese Traditional/methods* ; Artificial Intelligence ; Network Pharmacology/methods* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Drug Discovery

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

Liver transplantation (LT) has become a standard treatment for end-stage liver diseases, and graft injury is intricately associated with poor prognosis. Granzyme B (GZMB) plays a vital role in natural killer (NK) cell biology, but whether NK-derived GZMB affects graft injury remains elusive. Through the analysis of single-cell RNA-sequencing data obtained from human LT grafts and the isolation of lymphocytes from mouse livers following ischemia-reperfusion injury (IRI), we demonstrated that 2NK cells with high expression of GZMB are enriched in patients and mice. Both systemically and liver-targeted depletion of NK cells led to a notable reduction in GZMB⁺ cell infiltration, subsequently resulting in diminished graft injury. Notably, the reconstitution of Il2rg ^-/- Rag2 ^-/- mice with purified Gzmb-KO NK cells demonstrated superior outcomes compared to those with wild-type NK cells. Crucially, global knockout of GZMB and pharmacological inhibition exhibited remarkable improvements in liver function in both mouse IRI and rat LT models. Moreover, a phosphorylated derivative of FDA-approved vidarabine was identified as an effective inhibitor of mouse GZMB activity by molecular dynamics, which could provide a potential avenue for therapeutic intervention. Therefore, targeting NK cell-derived GZMB during the LT process suggests potential therapeutic strategies to improve post-transplant outcomes.

Objectives To identify key clinical factors influencing recurrence in osteosarcoma patients,to construct and validate a Nomogram-based recurrence risk prediction model,thereby providing a quantitative tool for clinical decision-making and recurrence prevention/control.Methods Clinical data of 469 osteosarcoma patients admitted to Yunnan Cancer Hospital between 2013～2022 were retrospectively collected.Statistical analysis was performed using R software(version 4.3.2).Potential influencing factors were initially screened via univariate analysis and LASSO regression analysis.Independent predictors of osteosarcoma recurrence were then identified using multivariate logistic regression analysis.Based on the identified independent factors,a Nomogram prediction model for recurrence risk was constructed.The area under the receiver operating characteristic curve(AUC)was used to evaluate the model's discriminative ability.Results Among the entire cohort,68 patients experienced recurrence,yielding a recurrence rate of 14.50%.Multivariate analysis identified the following as independent predictors of recurrence:Primary Tumor Location:Tibial lesions(P=0.009)were associated with a significantly lower recurrence risk compared to femoral lesions(OR=0.297),while lesions in"Other Bones"(P=0.008)carried a significantly higher risk(OR=3.294).Biopsy Method:Needle biopsy(P=0.033)was associated with a significantly lower recurrence risk compared to open biopsy(OR=0.461).Lung Metastasis Status:Patients with lung metastasis(P<0.001)had a significantly higher recurrence risk than those without(OR=11.873).Lymphocyte Count:A higher lymphocyte count(P=0.001)was a protective factor,associated with a lower recurrence risk(OR=0.450).The constructed Nomogram prediction model demonstrated excellent performance:Validation results showed an AUC=0.842(95%CI:0.806～0.875),indicating outstanding discriminative ability.Conclusions This study successfully constructed and validated a Nomogram prediction model for osteosarcoma recurrence risk integrating key clinical factors.The model demonstrates superior discriminative ability and can accurately and quantitatively assess the recurrence risk for individual patients.This tool thus provides critical reference for guiding clinical treatment decisions.

Objective: To improve the efficiency and standardization of preoperative anemia diagnosis and treatment by establishing a systematic intelligent management platform for preoperative anemia. Methods: A multidisciplinary collaborative model was adopted to develop a preoperative anemia management system that integrates intelligent early warning, standardized treatment pathways, and quality control. The system utilizes natural language processing technology to automatically capture laboratory data and establish evidence-based medical decision support functions. A pre-post study design was employed to compare changes in preoperative anemia screening rates, preoperative anemia intervention rates, reasonable use of iron supplements, and perioperative red blood cell transfusion rates before and after system implementation. Results: After system implementation, the standardization of anemia diagnosis and treatment significantly improved: 1) Screening effectiveness: The anemia screening rate increased to 50.00% (an increase of 27.24%); 2) Intervention effectiveness: The anemia treatment rate rose to 56.30% (an increase of 14.02%); 3) Treatment standardization: The reasonable use rate of iron supplements increased to 55.33% (an increase of 21.02%); the red blood cell transfusion rate decreased to 18.29% (a decrease of 4.07%), and the amount of red blood cell transfusions was reduced by 291 units. Conclusion: This system achieves full-process management of preoperative anemia through information technology, significantly enhancing the standardization of diagnosis and treatment as well as intervention effectiveness, providing an effective solution for perioperative anemia management.

Objective: To investigate the influencing factors for cognitive function among aluminum workers, so as to provide the basis for intervention and prevention of cognitive function among aluminum-exposed populations. Methods: From July to August 2019, male aluminum workers in the electrolytic aluminum workshop of an aluminum factory in Shanxi Province were selected using the cluster sampling method. Demographic information, prevalence of chronic diseases, lifestyle behaviors, night shifts, and sleep quality were collected through questionnaire surveys. Blood aluminum levels were measured using inductively coupled plasma-mass spectrometry. Cognitive function was investigated using the Montreal Cognitive Assessment. Factors affecting cognitive function among aluminum workers were analyzed by a quantile regression model. Results: A total of 142 aluminum workers were surveyed, including 57 workers aged 20 to <40 years (40.14%) and 85 workers aged 40 to 60 years (59.86%). The median blood aluminum level was 38.23 (interquartile range, 21.82) μg/L. The median cognitive function score was 24.00 (interquartile range, 3.00) points. Quantile regression analysis revealed that older age (βQ5=-0.186, 95%CI: -0.269 to -0.102), lower educational level (βQ5=1.933, 95%CI: 1.029 to 2.838; βQ10=1.743, 95%CI: 0.480 to 3.006; βQ50=1.038, 95%CI: 0.141 to 1.935; βQ75=1.006, 95%CI: 0.437 to 1.575; βQ90=1.111, 95%CI: 0.291 to 1.930), smoking (βQ5=-2.056, 95%CI: -3.264 to -0.849), alcohol consumption (βQ5=-1.821, 95%CI: -3.247 to -0.396) and higher blood aluminum level (βQ5=-0.075, 95%CI: -0.110 to -0.040; βQ10=-0.078, 95%CI: -0.127 to -0.029; βQ50=-0.075, 95%CI: -0.110 to -0.040; βQ75=-0.057, 95%CI: -0.079 to -0.035; βQ90=-0.067, 95%CI: -0.099 to -0.035) were associated with cognitive function decline among aluminum workers. Conclusions Educational level and blood aluminum level are the main factors affecting the cognitive function among aluminum workers. Among those with lower cognitive function scores, age, smoking and alcohol consumption are also associated with cognitive function.

Resistance to poly adenosine diphosphate (ADP)-ribose polymerase inhibitor (PARPi) presents a considerable obstacle in the treatment of ovarian cancer. F-box and tryptophan-aspartic (WD) repeat domain containing 11 (FBXW11) modulates the ubiquitination of growth-and invasion-related factors in lung cancer, colorectal cancer, and osteosarcoma. The function of FBXW11 in PARPi therapy is still ambiguous. In this study, RNA sequencing (RNA-seq) showed that FBXW11 expression was raised in ovarian cancer cells that had been treated with PARPi. FBXW11 was abnormally expressed at low levels in high-grade serous ovarian cancer (HGSOC) tissues, and low levels of FBXW11 were associated with shorter overall survival (OS) and progression-free survival (PFS) in HGSOC patients. Overexpressing FBXW11 made ovarian cancer more sensitive to PARPi, while knocking down FBXW11 made it less sensitive. The four-dimensional (4D) label-free quantitative proteomic analysis revealed that FBXW11 targeted S100 calcium binding protein A11 (S100A11) and promoted its degradation through ubiquitination. The increased degradation of S100A11 led to less efficient DNA damage repair, which in turn contributed to increased PARPi-induced DNA damage. The role of FBXW11 in promoting PARPi sensitivity was also confirmed in xenograft mouse models. In summary, our study confirms that FBXW11 promotes the susceptibility of ovarian cancer cells to PARPi via affecting S100A11-mediated DNA damage repair.

Coptis chinensis Franch. and Panax ginseng C. A. Mey. are traditional herbal medicines with millennia of documented use and broad therapeutic applications, including anti-diabetic properties. However, the synergistic effect of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng on type 2 diabetes mellitus (T2DM) and its underlying mechanism remain unclear. The research demonstrated that the optimal ratio of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng was 4∶1, exhibiting maximal efficacy in improving insulin resistance and gluconeogenesis in primary mouse hepatocytes. This combination demonstrated significant synergistic effects in improving glucose tolerance, reducing fasting blood glucose (FBG), the weight ratio of epididymal white adipose tissue (eWAT), and the homeostasis model assessment of insulin resistance (HOMA-IR) in leptin receptor-deficient (db/db) mice. Subsequently, a T2DM liver-specific network was constructed based on RNA sequencing (RNA-seq) experiments and public databases by integrating transcriptional properties of disease-associated proteins and protein-protein interactions (PPIs). The network recovery index (NRI) score of the combined treatment group with a 4∶1 ratio exceeded that of groups treated with individual components. The research identified that activated adenosine 5'-monophosphate-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling in the liver played a crucial role in the synergistic treatment of T2DM, as verified by western blot experiment in db/db mice. These findings demonstrate that the 4∶1 combination of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng significantly improves insulin resistance and glucose and lipid metabolism disorders in db/db mice, surpassing the efficacy of individual treatments. The synergistic mechanism correlates with enhanced AMPK/ACC signaling pathway activity.
Animals ; Panax/chemistry* ; Ginsenosides/administration & dosage* ; Diabetes Mellitus, Type 2/metabolism* ; Mice ; Male ; Alkaloids/pharmacology* ; Coptis/chemistry* ; Drug Synergism ; Insulin Resistance ; Mice, Inbred C57BL ; Humans ; Transcriptome/drug effects* ; Blood Glucose/metabolism* ; Hypoglycemic Agents/administration & dosage* ; Drugs, Chinese Herbal/administration & dosage* ; Hepatocytes/metabolism*