ObjectiveRetinal vein occlusion （RVO） is the second most common vascular disease leading to vision loss. Since its pathogenesis remains unclear， current Western medical treatments primarily target complications such as macular edema and neovascularization. The main therapeutic approaches include intravitreal injections of anti-vascular endothelial growth factor （VEGF） agents or corticosteroids， laser photocoagulation， and pars plana vitrectomy. However， these treatments cannot fully reverse disease progression or structural damage. Traditional Chinese medicine （TCM） has unique advantages in the clinical diagnosis and treatment of RVO， and integrated Chinese and Western medicine approaches may offer better clinical outcomes. This study， based on the clinical manifestations of RVO， systematically reviews the existing literature and evaluates the alignment of current RVO animal models with clinical manifestations. The aim is to identify the characteristics and limitations of existing models and provide recommendations and prospects for developing RVO animal models featuring the combination of disease and syndrome. MethodsDatabases including CNKI， Wanfang Data， PubMed， and Web of Science were searched with the keywords of "retinal vein occlusion" and "animal model". Model characteristics were assessed based on the diagnostic criteria for diseases and syndromes in both TCM and Western medicine. The alignment of each model with clinical manifestations was analyzed and evaluated. ResultsThe available RVO models were primarily established via methods such as laser photocoagulation， photodynamic therapy， diathermy， intravitreal drug injection， and mechanical modeling. These models demonstrated moderate overall alignment with clinical manifestations， mainly reflecting disease characteristics. However， they generally lack representation of TCM syndrome features. ConclusionExisting RVO models are predominantly based on Western medicine and lack TCM syndrome features. Western medical treatments for RVO have certain limitations， while syndrome differentiation and treatment in TCM offer potential advantages. Future research should focus on developing disease-syndrome integrated animal models that incorporate both pathological features and TCM syndrome characteristics. This approach will enhance the design of RVO models and facilitate both basic and clinical research， which make it a scientifically valuable and necessary endeavor.

ObjectiveRetinal vein occlusion （RVO） is the second most common vascular disease leading to vision loss. Since its pathogenesis remains unclear， current Western medical treatments primarily target complications such as macular edema and neovascularization. The main therapeutic approaches include intravitreal injections of anti-vascular endothelial growth factor （VEGF） agents or corticosteroids， laser photocoagulation， and pars plana vitrectomy. However， these treatments cannot fully reverse disease progression or structural damage. Traditional Chinese medicine （TCM） has unique advantages in the clinical diagnosis and treatment of RVO， and integrated Chinese and Western medicine approaches may offer better clinical outcomes. This study， based on the clinical manifestations of RVO， systematically reviews the existing literature and evaluates the alignment of current RVO animal models with clinical manifestations. The aim is to identify the characteristics and limitations of existing models and provide recommendations and prospects for developing RVO animal models featuring the combination of disease and syndrome. MethodsDatabases including CNKI， Wanfang Data， PubMed， and Web of Science were searched with the keywords of "retinal vein occlusion" and "animal model". Model characteristics were assessed based on the diagnostic criteria for diseases and syndromes in both TCM and Western medicine. The alignment of each model with clinical manifestations was analyzed and evaluated. ResultsThe available RVO models were primarily established via methods such as laser photocoagulation， photodynamic therapy， diathermy， intravitreal drug injection， and mechanical modeling. These models demonstrated moderate overall alignment with clinical manifestations， mainly reflecting disease characteristics. However， they generally lack representation of TCM syndrome features. ConclusionExisting RVO models are predominantly based on Western medicine and lack TCM syndrome features. Western medical treatments for RVO have certain limitations， while syndrome differentiation and treatment in TCM offer potential advantages. Future research should focus on developing disease-syndrome integrated animal models that incorporate both pathological features and TCM syndrome characteristics. This approach will enhance the design of RVO models and facilitate both basic and clinical research， which make it a scientifically valuable and necessary endeavor.

Ulcerative colitis （UC） is a common digestive disease characterized by recurrence and remission alternation，which seriously affects the life quality and physical and mental health of patients. The pathogenesis of UC is complex，and studies have shown that the occurrence and development of UC are closely related to the transduction of multiple signaling pathways. The current western medicine treatment has many problems，such as single action target，more adverse reactions，poor patient tolerance，and easy recurrence after stopping the medicine. Traditional Chinese medicine has the advantages such as multi-targets，multi-pathways， and fewer adverse reactions， elucidating that the action mechanism of traditional Chinese medicine in the treatment of UC is the focus of current research. Therefore， this paper conducted a systematic review on how traditional Chinese medicine exerts therapeutic effects by regulating the signaling pathways related to UC in recent years，and it was found that traditional Chinese medicine can regulate nuclear factor-κB （NF-κB），adenylate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR），Janus tyrosine protein kinase （JAK）/signal transducer and activator of transcription （STAT），phosphatidylinositol 3-kinase （PI3K） /protein kinase B （Akt），NOD-like receptor thermoprotein structural domain-related protein 3 （NLRP3）/cysteine protease-1 （Caspase-1），nuclear respiratory factor 2 （Nrf2）/heme oxygenase-1 （HO-1）， and several other pathways，thereby inhibiting oxidative stress and cellular pyroptosis，regulating the Tregs/Th17 cellular balance， promoting autophagic response and M2-type macrophage polarization，restoring the diversity and abundance of intestinal flora，promoting the repair of intestinal mucosal barrier function，and alleviating the inflammatory damage of UC colonic tissues. The holistic concept and evidence-based treatment of traditional Chinese medicine were combined with the modern molecular mechanism research of traditional Chinese medicine， and the traditional Chinese medicine combinations with different mechanisms， following regulation， were formulated into compound formulas or pairs of medicines according to the pattern of evidence. It is expected to achieve better therapeutic efficacy and to provide ideas and references for the modification of classic compound formulae of traditional Chinese medicine in UC treatment and clinical translation.

Objective : To investigate the biomechanical effect of alveolar bone graft (ABG) resorption on the maxillary alveolar process under occlusal force in a patient with unilateral cleft lip and palate (UCLP) and provide evidence for the clinical application of ABG. Methods: A 3D finite element maxillary model of an 11-year-old female patient with UCLP was generated. The occlusal force was applied to six models with different ABG resorption, namely non-resorption, upper 1/3 resorption, upper 2/3 resorption, lower 1/3 resorption, lower 2/3 resorption, and upper&lower 1/3 resorption. The properties of structures in all models were set to be linear, elastic, and isotropic. The displacement and Von Mises stress of each reference node of the alveolar process were compared and analyzed. Results: Under occlusal force, the most significant displacement of the alveolar process was located in the anterior area, and it decreased gradually from anterior area to both sides in all groups. The displacement values of the alveolar process under cleft side lateral occlusion were as follows: non-resorption group < lower 2/3 resorption group < upper&lower 1/3 resorption group < lower 1/3 resorption group < upper 2/3 resorption group < upper 1/3 resorption group. The displacement values of the alveolar process under centric occlusion were as follows: non-resorption group < lower 1/3 resorption group < upper&lower 1/3 resorption group < upper 2/3 resorption group < lower 2/3 resorption group < upper 1/3 resorption group. The displacement values of the alveolar process under non-cleft side lateral occlusion were as follows: non-resorption group < lower 1/3 resorption group < upper 1/3 resorption group < lower 2/3 resorption group < upper&lower 1/3 resorption group < upper 2/3 resorption group. The stress was concentrated on the premolar area on the functional side of the alveolar process, followed by the canine and molar areas in all groups. The stress values of the alveolar process under cleft side lateral occlusion were as follows: non-resorption group < lower 2/3 resorption group < upper&lower 1/3 resorption group < upper 2/3 resorption group < lower 1/3 resorption group < upper 1/3 resorption group. The stress values of the alveolar process under centric occlusion were as follows: non-resorption group < upper 1/3 resorption group < lower 1/3 resorption group < lower 2/3 resorption group < upper&lower 1/3 resorption group < upper 2/3 resorption group. The stress values of the alveolar process under non-cleft side lateral occlusion were as follows: non-resorption group < lower 2/3 resorption group < upper&lower 1/3 resorption group < lower 1/3 resorption group < upper 2/3 resorption group < upper 1/3 resorption group. Under occlusal force, the displacement and stress of the alveolar process in the non-resorption model were significantly lower than those in other models. The displacement and stress of the alveolar process in the models with resorption in the lower area of the ABG were significantly lower than those in the models with resorption in the upper-middle areas of the ABG. Conclusion After unilateral complete cleft lip and palate bone grafting, the integrity and continuity of the middle and upper parts of the alveolar process bone grafting play a key role in the biomechanical status of the alveolar process. If bone resorption occurs in the above parts, bone grafting should be considered.

BACKGROUND:Metal-organic frameworks exhibited great potential for bone tissue engineering and bone disease treatment because of its unique merits including tunable porosity,a large specific surface area,good biocompatibility,and easy structure modification. OBJECTIVE:To review the advancements,application,strengths,and weaknesses of metal-organic framework materials in bone repair,arthritis,bone infection,and bone tumors,offering guidance and strategies for future research. METHODS:Web of Science,PubMed,and CNKI databases were searched using Chinese and English keywords"metal-organic frameworks,MOFs,orthopedics,bone repair,bone regeneration,orthopaedic applications,bone tissue engineering,bone infection,arthritis,bone tumor,osteosarcoma"for related literature published from 2015 to 2023.Following initial screening based on inclusion and exclusion criteria,72 articles were finally included for review. RESULTS AND CONCLUSION:(1)During bone repair,metal ions of metal-organic frameworks can induce bone formation by activating specific signaling pathways,which include stimulating osteogenic gene expression,inhibiting osteoclasts,encouraging blood vessel formation,and speeding up bone mineralization.Hence,metal-organic frameworks with metals like calcium,strontium,cobalt,copper,and magnesium ions show significant potential in enhancing bone implant performance.(2)Metal-organic framework materials,especially zinc/cobalt-based metal-organic frameworks,exhibit enzyme-like activities and promote cartilage regeneration by scavenging reactive oxygen species.Compared with natural enzymes,it has the advantages of not easy inactivation and better stability.(3)Zinc-based metal-organic framework materials characterized with wide band gaps,efficient separation and migration of photogenerated carriers,and high stability,the enhancement of photocatalytic activity results from enhancing the excited electron-hole widely used for the eradication of bacteria and tumor cells.(4)Bimetallic metal-organic frameworks,the doping of additional metals,showed critical advantages in optimizing structural performance,such as zinc/magnesium-based metal-organic framework 74 offering increased stability for durable antibacterial activity,and the light absorption capacity and photocatalytic efficiency of tantalum/zirconium-based metal-organic framework greatly improved and thus enhancing the radiation therapy.(5)However,metal-organic framework materials still face challenges in clinical applications,such as the uncertainty of drug release,in vivo safety,and potential immune responses from long-term presence.

Objective To explore the role of neogambogic acid in the characteristics of colorectal cancer stem cells (CRC-CSCs) through the Wnt/β-catenin signaling pathway. Methods The colorectal cells SW480 and HCT166 were divided into control group and neogambogic acid groups (1.5, 3, 6, and 12 μmol/L). The viability of CRC-CSCs was determined by MTT method, and spheroid and clone formation assays were used to assess the capacity of spheroid formation and self-renewal ability of the cells. The effects of neogambogic acid on the apoptosis and cell cycle of CRC-CSCs were evaluated by flow cytometry assays. Real-time quantitative PCR was used to detect the mRNA expression levels of relative markers (CD133, CD44, ALDH1, Oct4, and Nanog) of CRC-CSCs, and the protein expression levels of the self-renewal marker (PCNA), apoptosis markers (cleaved caspase-3 and cleaved caspase-9), and Wnt/β-catenin signaling pathway markers (p-GSK3β, GSK3β, β-catenin, and Wnt) were analyzed using Western blot. Results Compared with the control group, after neogambogic acid treatment, the viability of SW480 and HCT116 cells decreased (P<0.05), the spheroid forming ability and the clone numbers of CRC-CSCs decreased (P<0.001, P<0.01) but the cell apoptosis rate increased (P<0.01), and cell cycle was arrested in G₀/G₁ phase. Moreover, neogambogic acid downregulated the mRNA and protein expression of relative markers of CRC-CSCs (CD133, CD44, ALDH1, Oct4, and Nanog), PCNA, p-GSK3β, β-catenin, and Wnt (P<0.05) and upregulated the expression of cleaved caspase-3, cleaved caspase-9, and GSK3β (P<0.01). Conclusion Neogambogic can inhibit the stem cell properties of colorectal cells via inhibition of Wnt/β-catenin signaling pathway. As a result, neogambogic acid may be an attractive agent against colorectal cancer.

OBJECTIVES: We propose a low-dose CT image restoration method based on central guidance and alternating optimization (FedGP). METHODS: The FedGP framework revolutionizes the traditional federated learning model by adopting a structure without a fixed central server, where each institution alternatively serves as the central server. This method uses an institution-modulated CT image restoration network as the core of client-side local training. Through a federated learning approach of central guidance and alternating optimization, the central server leverages local labeled data to guide client-side network training to enhance the generalization capability of the CT imaging model across multiple institutions. RESULTS: In the low-dose and sparse-view CT image restoration tasks, the FedGP method showed significant advantages in both visual and quantitative evaluation and achieved the highest PSNR (40.25 and 38.84), the highest SSIM (0.95 and 0.92), and the lowest RMSE (2.39 and 2.56). Ablation study of FedGP demonstrated that compared with FedGP(w/o GP) without central guidance, the FedGP method better adapted to data heterogeneity across institutions, thus ensuring robustness and generalization capability of the model in different imaging conditions. CONCLUSIONS FedGP provides a more flexible FL framework to solve the problem of CT imaging heterogeneity and well adapts to multi-institutional data characteristics to improve generalization ability of the model under diverse imaging geometric configurations.
Tomography, X-Ray Computed/methods* ; Humans ; Radiation Dosage ; Image Processing, Computer-Assisted/methods* ; Algorithms

Vein graft (VG) failure (VGF) is associated with VG intimal hyperplasia, which is characterized by abnormal accumulation of vascular smooth muscle cells (VSMCs). Most neointimal VSMCs are derived from pre-existing VSMCs via a process of VSMC phenotypic transition, also known as dedifferentiation. There is increasing evidence to suggest that ginger or its bioactive ingredients may block VSMC dedifferentiation, exerting vasoprotective functions; however, the precise mechanisms have not been fully characterized. Therefore, we investigated the effect of ginger on VSMC phenotypic transition in VG remodeling after transplantation. Ginger significantly inhibited neointimal hyperplasia and promoted lumen (L) opening in a 3-month VG, which was primarily achieved by reducing ferroptotic stress. Ferroptotic stress is a pro-ferroptotic state. Contractile VSMCs did not die but instead gained a proliferative capacity and switched to the secretory type, forming neointima (NI) after vein transplantation. Ginger and its two main vasoprotective ingredients (6-gingerol and 6-shogaol) inhibit VSMC dedifferentiation by reducing ferroptotic stress. Network pharmacology analysis revealed that 6-gingerol inhibits ferroptotic stress by targeting P53, while 6-shogaol inhibits ferroptotic stress by targeting 5-lipoxygenase (Alox5), both promoting ferroptosis. Furthermore, both ingredients co-target peroxisome proliferator-activated receptor gamma (PPARγ), decreasing PPARγ-mediated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (Nox1) expression. Nox1 promotes intracellular reactive oxygen species (ROS) production and directly induces VSMC dedifferentiation. In addition, Nox1 is a ferroptosis-promoting gene that encourages ferroptotic stress production, indirectly leading to VSMC dedifferentiation. Ginger, a natural multi-targeted ferroptotic stress inhibitor, finely and effectively prevents VSMC phenotypic transition and protects against venous injury remodeling.

This study investigates the clinical differentiation and treatment strategies for bipolar disorder （BD） by analyzing the relationship of its core pathomechanisms including qi stagnation， blood stasis， phlegm turbidity， and heat constraint with bile acid metabolism. The imbalance of "yin in form and yang in function" leads to qi stagnation， blood stasis， phlegm turbidity， and heat constraint， which are critical in the pathogenesis and progression of BD. Bile acids regulate neuroinflammation， neural plasticity， and intestinal flora homeostasis through receptor-mediated pathways. It is believed that the physiological functions of bile acids concretely embody the concept of the "liver is yin in form and yang in function" theory. Clinically， prescriptions such as Sini Powder （四逆散） with the function of venting pathogen and resolving constraint， Wendan Decoction （温胆汤） of drying dampness and resolving phlegm， Longdan Xiegan Decoction （龙胆泻肝汤） of clearing liver and draining fire， and Huanglian Ejiao Decoction （黄连阿胶汤） of nourishing yin and blood can be used to nourish liver yin and restore liver yang function. These strategies may improve BD prognosis by modulating bile acid synthesis and metabolism.

Objective: To explore the therapeutic mechanism of puerarin in treating rheumatoid arthritis (RA) rats based on the serine/tyrosine protein kinase B (AKT)-phosphorylated forkhead box protein O1 (FOXO1)-interleukin-9 (AKT-FOXO1-IL-9) signaling pathway. Methods : 36 rats were randomly divided into a blank group , a model group , a positive control group , and low , medium , and high dose groups of puerarin. Except for the blank group , the other groups were induced with type Ⅱ collagen to establish a RA rat model. After successful modeling , different doses of puerarin and methotrexate were given to treat the rats. The body mass and toe thickness of the rats were measured , and biochemical indicators of rat blood rheology were detected. X-ray was used to observe changes in rat joint morphology. Safranin green staining were used to observe the pathology of rat joint tissue. ELISA was used to detect the levels of IL-9 and rheumatoid factors in rat serum , and Western blot was used to detect changes in levels of AKT and FOXO1 . 36 rats were randomly divided into a blank group , a model group , a positive control group , and low , medium , and high dose groups of puerarin. Except for the blank group , the other groups were induced with type Ⅱ collagen to establish a RA rat model. After successful modeling , different doses of puerarin and methotrexate were given to treat the rats. The body mass and toe thickness of the rats were measured , and biochemical indicators of rat blood rheology were detected. X-ray was used to observe changes in rat joint morphology. Safranin green staining were used to observe the pathology of rat joint tissue. ELISA was used to detect the levels of IL-9 and rheumatoid factors in rat serum , and Western blot was used to detect changes in levels of AKT and FOXO1 . Results: Compared with the blank group , the model group had the lowest toe thickness , and X-ray images showed more obvious segmental stenosis and more severe marginal bone invasion ; scaly like changes appeared at the edges of joints stained with safranin green , accompanied by the exudation of inflammatory cells and increased proliferation and secretion of chondrocytes ; the expression levels of inflammatory factors IL-9 and rheumatoid factors were the highest , and the expression levels of AKT and FOXO1 proteins were the highest (P < 0. 05) . Compared with the model group , the toe thickness of rats treated with different doses of puerarin decreased ; X-ray images showed that the puerarin treatment group of rats showed improvement in plantar joint stenosis and marginal bone invasion ; the results of safranin green staining showed that after treatment with different doses of puerarin , the infiltration of inflammatory cells decreased , and the expression levels of inflammatory factor IL-9 , rheumatoid factors , AKT , and FOXO1 proteins decreased significantly ( P < 0. 05 ) , with the high-dose puerarin group showing the most significant difference. Compared with the high-dose puerarin group , the positive control group showed a significant decrease in the above results and statistical differences (P < 0. 05) . Conclusion Puerarin has a good therapeutic effect on rats with RA by inhibiting the AKT-FOXO1-IL-9 pathway. The high-dose puerarin group (60 mg/kg) has the best therapeutic effect and the results show a dose-response relationship.