ObjectiveTo establish a rat model of osteoarthritis and study the anti-inflammatory effects and mechanisms of fraxetin. MethodsEighteen 8-week-old male SPF-grade SD rats were randomly divided into three groups: Rats in the blank group received a right articular cavity injection of 50 μL of normal saline for 1 week; the model and intervention groups were injected with monosodium iodoacetate (MIA) into the right joint cavity to induce osteoarthritis, while the intervention group subsequently received fraxetin (5 mg·kg^-1·d^-1) for 1 week. Four weeks after drug intervention, abdominal aortic blood was collected. The animals were then euthanized, and knee joint cartilage were collected. The cartilage samples were stained with hematoxylin-eosin, safranin O-fast green, and toluidine blue for histopathological examination and scoring using the Mankin and OARSI scoring systems. The trabecular bone volume/total volume (Tb.BV/TV), trabecular bone surface density/total volume (Tb.BS/TV), and trabecular number (Tb.N) of each group were compared and analyzed using a micro-CT scanning system. The expression levels of various inflammatory factors [tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6)], and cartilage oligomeric matrix protein (COMP) were measured using enzyme-linked immunosorbent assay (ELISA). The expression levels of mitogen-activated protein kinase p38 (p38 MAPK), phosphorylation-p38 MAPK (p-p38 MAPK), c-Jun N-terminal kinase (JNK), and phosphorylation-JNK (p-JNK) were measured by western blotting. ResultsThe staining of cartilage sections of rat knee joints showed that the articular surface defects in the model group were severe, while the cartilage destruction in the intervention group was relatively reduced. Micro-CT results showed that Tb.BV/TV, Tb.BS/TV and Tb.N in the intervention group were significantly higher than those in the model group (P < 0.05); the Mankin score in the model group was significantly higher than that in the blank group (P < 0.05), the Mankin score in the intervention group was significantly lower than that in the model group (P < 0.05); while the OARSI score in the intervention group was significantly lower than that in the model group (P < 0.05). The results of the enzyme-linked immunosorbent assay showed that the serum levels of TNF-α, IL-1β, IL-6, and COMP in the model group were significantly higher than those in the blank group (all P < 0.05), while those in the intervention group were significantly lower than in the model group (P < 0.05). Western blot results showed that the expression levels of p-p38 MAPK and p-JNK in the knee cartilage tissue were significantly lower in the intervention group than in the model group (both P < 0.05), and significantly higher in the model group than in the blank group (both P < 0.05). ConclusionFraxetin may play a therapeutic role in a monosodium iodoacetate-induced rat model of osteoarthritis through the p38 MAPK pathway.

ObjectiveTo establish a rat model of osteoarthritis and study the anti-inflammatory effects and mechanisms of fraxetin. MethodsEighteen 8-week-old male SPF-grade SD rats were randomly divided into three groups: Rats in the blank group received a right articular cavity injection of 50 μL of normal saline for 1 week; the model and intervention groups were injected with monosodium iodoacetate (MIA) into the right joint cavity to induce osteoarthritis, while the intervention group subsequently received fraxetin (5 mg·kg^-1·d^-1) for 1 week. Four weeks after drug intervention, abdominal aortic blood was collected. The animals were then euthanized, and knee joint cartilage were collected. The cartilage samples were stained with hematoxylin-eosin, safranin O-fast green, and toluidine blue for histopathological examination and scoring using the Mankin and OARSI scoring systems. The trabecular bone volume/total volume (Tb.BV/TV), trabecular bone surface density/total volume (Tb.BS/TV), and trabecular number (Tb.N) of each group were compared and analyzed using a micro-CT scanning system. The expression levels of various inflammatory factors [tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6)], and cartilage oligomeric matrix protein (COMP) were measured using enzyme-linked immunosorbent assay (ELISA). The expression levels of mitogen-activated protein kinase p38 (p38 MAPK), phosphorylation-p38 MAPK (p-p38 MAPK), c-Jun N-terminal kinase (JNK), and phosphorylation-JNK (p-JNK) were measured by western blotting. ResultsThe staining of cartilage sections of rat knee joints showed that the articular surface defects in the model group were severe, while the cartilage destruction in the intervention group was relatively reduced. Micro-CT results showed that Tb.BV/TV, Tb.BS/TV and Tb.N in the intervention group were significantly higher than those in the model group (P < 0.05); the Mankin score in the model group was significantly higher than that in the blank group (P < 0.05), the Mankin score in the intervention group was significantly lower than that in the model group (P < 0.05); while the OARSI score in the intervention group was significantly lower than that in the model group (P < 0.05). The results of the enzyme-linked immunosorbent assay showed that the serum levels of TNF-α, IL-1β, IL-6, and COMP in the model group were significantly higher than those in the blank group (all P < 0.05), while those in the intervention group were significantly lower than in the model group (P < 0.05). Western blot results showed that the expression levels of p-p38 MAPK and p-JNK in the knee cartilage tissue were significantly lower in the intervention group than in the model group (both P < 0.05), and significantly higher in the model group than in the blank group (both P < 0.05). ConclusionFraxetin may play a therapeutic role in a monosodium iodoacetate-induced rat model of osteoarthritis through the p38 MAPK pathway.

Antibody (Ab) humanization is critical to reduce immunogenicity and enhance efficacy in the preclinical phase of the development of therapeutic Abs originated from animal models. Computational suggestions have long been desired, but available tools focused on immunogenicity calculation of whole Ab sequences and sequence segments, missing the individual residue sites. This study introduces Site-specific Immunogenicity for Therapeutic Antibody (SITA), a novel computational framework that predicts B-cell immunogenicity score for not only the overall antibody, but also individual residues, based on a comprehensive set of amino acid descriptors characterizing physicochemical and spatial features for antibody structures. A transfer-learning-inspired framework was purposely adopted to overcome the scarcity of Ab-Ab structural complexes. On an independent testing dataset derived from 13 Ab-Ab structural complexes, SITA successfully predicted the epitope sites for Ab-Ab structures with a receiver operating characteristic (ROC)-area unver the ROC curve (AUC) of 0.85 and a precision-recall (PR)-AUC of 0.305 at the residue level. Furthermore, the SITA score can significantly distinguish immunogenicity levels of whole human Abs, therapeutic Abs and non-human-derived Abs. More importantly, analysis of an additional 25 therapeutic Abs revealed that over 70% of them were detected with decreased immunogenicity after modification compared to their parent variants. Among these, nearly 66% Abs successfully identified actual modification sites from the top five sites with the highest SITA scores, suggesting the ability of SITA scores for guide the humanization of antibody. Overall, these findings highlight the potential of SITA in optimizing immunogenicity assessments during the process of therapeutic antibody design.

Objective:To investigate the clinical features and prognostic factors of newly-treated elderly acute myeloid leukemia (AML) patients with intermediate-risk karyotype.Methods:A retrospective case series study was conducted. A total of 87 newly-treated elderly AML patients with intermediate-risk karyotype in the First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) from January 2013 to December 2023 were selected. The clinical characteristics were summarized. The Kaplan-Meier method was used for survival analysis and Cox proportional hazards model was used to make univariate and multivariate analyses of prognostic factors.Results:The median age [ M ( Q1, Q3)] of 87 patients was 69 (60, 87) years. The patients with normal karyotype and abnormal karyotype accounted for 77.1% (67/87), 22.9% (20/87), respectively. A total of 74 patients (85.1%) had 1 or more gene mutations, of which FLT3-ITD, NPM1 mutation, CEBPA mutation and WT1 high expression accounted for 29.9% (26/87), 26.4% (23/87), 19.5% (17/87), and 65.5% (57/87), respectively; additionally, 44.7% (39/87) of patients had 2 or more gene mutations. The objective response rate of patients after induction therapy was 47.7% (41/87), while the relapse rate was 73.2% (30/41). The median progression-free survival (PFS) time was 7.8 months, and the median overall survival (OS) time was 12.1 months. Univariate analysis result revealed that age, FLT3-ITD, hypomethylating agents, and minimal residual disease complete remission (MDR-CR) were factors influencing the OS of newly-treated elderly AML patients with intermediate-risk karyotype (all P < 0.05). Multivariate analysis indicated that MDR-CR was an independent risk factor for OS (yes vs. no: HR = 0.27, 95% CI: 0.14-0.51, P < 0.001). Conclusions:Newly-treated elderly AML patients with intermediate-risk karyotype have a high relapse rate and poor prognosis, and MDR-CR is identified as an independent influencing factor for the prognosis of these patients.

Paying for TCM according to the value of efficacy is an intrinsic requirement for establishing an effective and efficient diversified medical insurance payment method, and is also an important measure to support the inheritance, innovation and development of TCM. This study used text mining and PMC index model to quantitatively analyze and evaluate the texts of 20 special policies on payment based on efficacy value in TCM. It was found that there were 6 excellent policies, 14 acceptable policies, and there were no undesirable policies or perfect policies; overall, the average policy PMC index was 6.94, and the average provincial policy was 7.06, which was higher than the prefecture-level average of 6.27; the overall quality of special policies of TCM based on efficacy value was relatively high, but there was still much room for improvement in terms of policy timeliness, policy evaluation, policy measures, policy tools, and balance of policy design between provinces and cities.

Objective:Based on the investigation on the advantages of Traditional Chinese Medicine(TCM)participation in the field of basic public health services,exploring how TCM participates in public health.Methods:It searched for policies related to basic public health services and conducted a questionnaire survey on 2 995 people working in public health-related jobs in Beijing to conduct an empirical study on the advantages of Chinese medicine and the current status of participation.Results:2 982 valid questionnaires were collected,and practitioners in the field of public health services in Beijing had a high level of attention and recognition towards the participation of TCM.TCM is generally considered to have obvious advantages in basic public health services such as responding to epidemics,preventing and treating chronic diseases,and managing the health of Children 0-6 Years and the elderly.However,TCM shows overall shortcomings in emphasis,talent allocation,infrastructure construction,public perception and resource balance.Conclusion:To play the ascendant role and enhance the service capacity of TCM,basic public health services can be further developed by optimizing mechanisms related to the participation of TCM in disease prevention and control,chronic disease management,children's,and elderly health management.Basic public health services can enhance the service capacity of TCM from several aspects such as increasing financial support,strengthening the cultivation and management of TCM talents,and emphasizing grassroots and balanced resource allocation of TCM.

Objective:Based on the investigation on the advantages of Traditional Chinese Medicine(TCM)participation in the field of basic public health services,exploring how TCM participates in public health.Methods:It searched for policies related to basic public health services and conducted a questionnaire survey on 2 995 people working in public health-related jobs in Beijing to conduct an empirical study on the advantages of Chinese medicine and the current status of participation.Results:2 982 valid questionnaires were collected,and practitioners in the field of public health services in Beijing had a high level of attention and recognition towards the participation of TCM.TCM is generally considered to have obvious advantages in basic public health services such as responding to epidemics,preventing and treating chronic diseases,and managing the health of Children 0-6 Years and the elderly.However,TCM shows overall shortcomings in emphasis,talent allocation,infrastructure construction,public perception and resource balance.Conclusion:To play the ascendant role and enhance the service capacity of TCM,basic public health services can be further developed by optimizing mechanisms related to the participation of TCM in disease prevention and control,chronic disease management,children's,and elderly health management.Basic public health services can enhance the service capacity of TCM from several aspects such as increasing financial support,strengthening the cultivation and management of TCM talents,and emphasizing grassroots and balanced resource allocation of TCM.

Objective:Based on the investigation on the advantages of Traditional Chinese Medicine(TCM)participation in the field of basic public health services,exploring how TCM participates in public health.Methods:It searched for policies related to basic public health services and conducted a questionnaire survey on 2 995 people working in public health-related jobs in Beijing to conduct an empirical study on the advantages of Chinese medicine and the current status of participation.Results:2 982 valid questionnaires were collected,and practitioners in the field of public health services in Beijing had a high level of attention and recognition towards the participation of TCM.TCM is generally considered to have obvious advantages in basic public health services such as responding to epidemics,preventing and treating chronic diseases,and managing the health of Children 0-6 Years and the elderly.However,TCM shows overall shortcomings in emphasis,talent allocation,infrastructure construction,public perception and resource balance.Conclusion:To play the ascendant role and enhance the service capacity of TCM,basic public health services can be further developed by optimizing mechanisms related to the participation of TCM in disease prevention and control,chronic disease management,children's,and elderly health management.Basic public health services can enhance the service capacity of TCM from several aspects such as increasing financial support,strengthening the cultivation and management of TCM talents,and emphasizing grassroots and balanced resource allocation of TCM.

Objective:Based on the investigation on the advantages of Traditional Chinese Medicine(TCM)participation in the field of basic public health services,exploring how TCM participates in public health.Methods:It searched for policies related to basic public health services and conducted a questionnaire survey on 2 995 people working in public health-related jobs in Beijing to conduct an empirical study on the advantages of Chinese medicine and the current status of participation.Results:2 982 valid questionnaires were collected,and practitioners in the field of public health services in Beijing had a high level of attention and recognition towards the participation of TCM.TCM is generally considered to have obvious advantages in basic public health services such as responding to epidemics,preventing and treating chronic diseases,and managing the health of Children 0-6 Years and the elderly.However,TCM shows overall shortcomings in emphasis,talent allocation,infrastructure construction,public perception and resource balance.Conclusion:To play the ascendant role and enhance the service capacity of TCM,basic public health services can be further developed by optimizing mechanisms related to the participation of TCM in disease prevention and control,chronic disease management,children's,and elderly health management.Basic public health services can enhance the service capacity of TCM from several aspects such as increasing financial support,strengthening the cultivation and management of TCM talents,and emphasizing grassroots and balanced resource allocation of TCM.

Objective:Based on the investigation on the advantages of Traditional Chinese Medicine(TCM)participation in the field of basic public health services,exploring how TCM participates in public health.Methods:It searched for policies related to basic public health services and conducted a questionnaire survey on 2 995 people working in public health-related jobs in Beijing to conduct an empirical study on the advantages of Chinese medicine and the current status of participation.Results:2 982 valid questionnaires were collected,and practitioners in the field of public health services in Beijing had a high level of attention and recognition towards the participation of TCM.TCM is generally considered to have obvious advantages in basic public health services such as responding to epidemics,preventing and treating chronic diseases,and managing the health of Children 0-6 Years and the elderly.However,TCM shows overall shortcomings in emphasis,talent allocation,infrastructure construction,public perception and resource balance.Conclusion:To play the ascendant role and enhance the service capacity of TCM,basic public health services can be further developed by optimizing mechanisms related to the participation of TCM in disease prevention and control,chronic disease management,children's,and elderly health management.Basic public health services can enhance the service capacity of TCM from several aspects such as increasing financial support,strengthening the cultivation and management of TCM talents,and emphasizing grassroots and balanced resource allocation of TCM.