BACKGROUND:Prolyl hydroxylase domain 2(PHD2)inhibitors can regulate bone metabolism and relieve osteoporosis in ovariectomized rats.cpd17 is a small molecule oral PHD2 inhibitor newly developed by China Pharmaceutical University.It is effective in the treatment of renal anemia with few side effects,but its effect on bone formation and bone resorption is still unclear. OBJECTIVE:To investigate the effects of cpd17 on mouse osteogenic precursor cells. METHODS:Osteogenic precursor cells were treated with cpd17.Alkaline phosphatase activity and extracellular matrix mineralization were measured,and the expression levels of osteogenesis-and osteoclastogenesis-related markers,as well as PHD2 and hypoxia-inducible factor 1α,were detected.After inhibition of the hypoxia-inducible factor 1α pathway using LW6(a hypoxia-inducible factor 1α pathway inhibitor),alkaline phosphatase activity and extracellular matrix mineralization were detected again,as well as the expression levels of osteogenesis-and osteoclastogenesis-related markers,PHD2 and hypoxia-inducible factor 1α. RESULTS AND CONCLUSION:cpd17 significantly enhanced alkaline phosphatase activity and extracellular matrix mineralization,up-regulated the expression of osteogenesis-related markers,down-regulated the expression of osteoclastogenesis-related markers,up-regulated the expression of hypoxia-inducible factor 1α,down-regulate the expression of PHD2.However,cpd17's effects were significantly attenuated by LW6.To conclude,the PHD2 inhibitor cpd17 promotes osteogenic differentiation and inhibits osteoclastic differentiation through activation of the hypoxia-inducible factor 1α signaling pathway.

OBJECTIVE: To investigate the safety and effectiveness of using the Taylor spatial frame (TSF) based on the Ilizarov tension-stress principle for treatment of post-burn foot and ankle deformities in adults. METHODS: A clinical data of 6 patients with post-burn foot and ankle deformities treated between April 2019 and November 2023 was retrospectively analyzed. There was 1 male and 5 females with an average age of 28.7 years (range, 20-49 years). There were 3 cases of simple ankle equinus, 2 cases of ankle equinus, midfoot rocker-bottom foot, and forefoot pronation, and 1 case of calcaneus foot and forefoot pronation. Preoperative American Orthopedic Foot and Ankle Society (AOFAS) score was 45.3±18.2, 12-Item Short-Form Health Survey (SF-12)-Physical Component Summary (PCS) score was 34.3±7.3 and Mental Component Summary (MCS) score was 50.4±8.8. Imaging examination showed tibial-calcaneal angle of (79.8±31.5)°, calcaneus-first metatarsal angle of (154.5±45.3)°, talus-first metatarsal angle of (-19.3±35.0)°. Except for 1 case with severe deformity that could not be measured, the remaining 5 cases had talus-second metatarsal angle of (40.6±16.4)°. The deformities were fixed with TSF after soft tissue release and osteotomy. Then, the residual deformities were gradually corrected according to software-calculated prescriptions. TSF was removed after maximum deformity correction and osteotomy healing. External fixation time, brace wearing time after removing the TSF, and pin tract infection occurrence were recorded. Infection severity was evaluated based on Checketts-Otterburns grading. Joint function was evaluated using AOFAS score and SF-12 PCS and MCS scores. Patient satisfaction was assessed using Likert score. Imaging follow-up measured relevant indicators to evaluate the degree of deformity correction. Deformity recurrence was observed during follow-up. RESULTS: The external fixation time was 103-268 days (mean, 193.5 days). The mild pin tract infections occurred during external fixation in all patients, which healed after pin tract care and oral antibiotics. No serious complication such as osteomyelitis, fractures, neurovascular injury, or skin necrosis occurred. After external fixation removal, 3 cases did not wear braces, while the remaining 3 cases wore braces continuously for 6 weeks, 8 weeks, and 3 years, respectively. All patients were followed up 13.9-70.0 months, with an average of 41.7 months. During follow-up, none of the 6 patients had recurrence of foot deformity. At 1 year after operation, the AOFAS score was 70.0±18.1, SF-12-PCS and MCS scores were 48.9±4.5 and 58.8±6.4, respectively, all showing significant improvement compared to preoperative values ( P<0.05). Imaging follow-up showed that all osteotomies healed, and all distraction cases achieved bony union at 6 months after stopping stretching. At 1 year after operation, tibial-calcaneal angle was (117.5±12.8)° and talus-first metatarsal angle was (-3.3±19.3)°, both showing significant improvement compared to preoperative values ( P<0.05). Calcaneus-first metatarsal angle was (132.0±14.4)°, which also improved compared to preoperative values but without significant difference ( P>0.05). Except for 1 case with severe deformity that could not be measured, the remaining 5 cases had talus-second metatarsal angle of (18.0±6.4)°. And there was no significant difference ( P>0.05) between pre-and post-operative data of 4 patients with complete data. At 1 year after operation, 1 patient was satisfied with effectiveness and 5 patients were very satisfied. CONCLUSION The TSF, by applying the Ilizarov tension-stress principle for gradual distraction and multi-planar adjustment, combined with soft tissue release and osteotomy, can effectively correct foot and ankle deformities after burns, especially equinus deformity with contracture of the posterior soft tissues of the lower leg. There are still limitations in treating cases with tight, adherent scars on the dorsum of the foot that require long-distance distraction. If necessary, a multidisciplinary approach combined with microsurgical techniques can be utilized.
Humans ; Adult ; Male ; Female ; Middle Aged ; Retrospective Studies ; External Fixators ; Young Adult ; Burns/complications* ; Foot Deformities, Acquired/etiology* ; Treatment Outcome ; Ilizarov Technique/instrumentation*

OBJECTIVES: To explore the mechanism of cinnamic acid (CA) for improving doxorubicin-induced myocardial injury (DIC) in mice. METHODS: Network pharmacology analysis was used to obtain the key targets of CA and DIC. Male C57BL/6J mice were randomized into Sham, DOX, CA (25, 50 and 100 mg/kg)+DOX, and CA+Ferrostatin-1+DOX groups, and their myocardial function and pathology were examined by echocardiography and HE staining. Serum levels of CK-MB, LDH, MDA, IL-6, TNF‑α and myocardial ROS level were detected, and the expression levels of TLR4 and ferroptosis pathway proteins in myocardial tissue were detected by Western blotting. Cultured murine cardiomyocytes (HL-1 cells) with or without transfection with a small interfering RNA targeting TLR4 (si-TLR4) were treated with DOX or Erastin, and the cellular ROS content was measured by DCFH-DA staining; the expression level of GPX4 was detected using immunofluorescence staining. RESULTS: Network pharmacology analysis suggested that CA may improve DIC through TLR4 signaling. DOX treatment caused obvious myocardial injury in mice, which showed significantly increased serum levels of CK-MB, LDH, MDA, IL-6, TNF-α and myocardial ROS level with decreased myocardial levels of SLC7A11 and GPX4 proteins and increased levels of TLR4 and PTGS2 proteins. All these changes in the mouse models were significantly alleviated by treatment with CA, and the mice receiving CA or ferrostatin-1 treatment exhibited increased myocardial expressions of SLC7A11 and GPX4 proteins and lowered expressions of TLR4 and PTGS2 proteins. In cultured HL-1 cells, treatment with DOX and Erastin both obviously increased intracellular ROS level and decreased cellular GPX4 expression level, and these changes were strongly attenuated by TLR4 interference. CONCLUSIONS CA, as a potent herbal monomer, can effectively alleviate DIC in mice by inhibiting TLR4-mediated ferroptosis.
Animals ; Ferroptosis/drug effects* ; Toll-Like Receptor 4/metabolism* ; Myocytes, Cardiac/metabolism* ; Mice, Inbred C57BL ; Mice ; Male ; Doxorubicin/adverse effects* ; Cinnamates/pharmacology* ; Signal Transduction ; Reactive Oxygen Species/metabolism*

Objective:Using primary care chronic disease management as a case,it aims to explore an economic incentive model for integrated primary healthcare services based on value pricing.Additionally,practical needs and implementation recommendations are proposed.Methods:With the help of the health technology assessment framework,it proposes that integrated health services can be priced through service effectiveness and service utility,and develops an economic incentive model with value pricing at its core based on the patient-centered incentive model for innovative healthcare services,including financing,payment,appraisal,and distribution,and puts forward feasible suggestions in the light of the needs and actuality of primary integrated services in China.Conclusion and Recommendation:The value-based pricing model for integrated health services serves as a theoretical foundation for the transformation of primary healthcare service functions and the enhancement of service dynamics,aligning with China's value-oriented service procurement strategy.This research contributes to the academic discourse by providing localized insights and a scholarly tone,contributing to the advancement of knowledge in the field.

Objective:Using primary care chronic disease management as a case,it aims to explore an economic incentive model for integrated primary healthcare services based on value pricing.Additionally,practical needs and implementation recommendations are proposed.Methods:With the help of the health technology assessment framework,it proposes that integrated health services can be priced through service effectiveness and service utility,and develops an economic incentive model with value pricing at its core based on the patient-centered incentive model for innovative healthcare services,including financing,payment,appraisal,and distribution,and puts forward feasible suggestions in the light of the needs and actuality of primary integrated services in China.Conclusion and Recommendation:The value-based pricing model for integrated health services serves as a theoretical foundation for the transformation of primary healthcare service functions and the enhancement of service dynamics,aligning with China's value-oriented service procurement strategy.This research contributes to the academic discourse by providing localized insights and a scholarly tone,contributing to the advancement of knowledge in the field.

Objective:Using primary care chronic disease management as a case,it aims to explore an economic incentive model for integrated primary healthcare services based on value pricing.Additionally,practical needs and implementation recommendations are proposed.Methods:With the help of the health technology assessment framework,it proposes that integrated health services can be priced through service effectiveness and service utility,and develops an economic incentive model with value pricing at its core based on the patient-centered incentive model for innovative healthcare services,including financing,payment,appraisal,and distribution,and puts forward feasible suggestions in the light of the needs and actuality of primary integrated services in China.Conclusion and Recommendation:The value-based pricing model for integrated health services serves as a theoretical foundation for the transformation of primary healthcare service functions and the enhancement of service dynamics,aligning with China's value-oriented service procurement strategy.This research contributes to the academic discourse by providing localized insights and a scholarly tone,contributing to the advancement of knowledge in the field.

Objective:Using primary care chronic disease management as a case,it aims to explore an economic incentive model for integrated primary healthcare services based on value pricing.Additionally,practical needs and implementation recommendations are proposed.Methods:With the help of the health technology assessment framework,it proposes that integrated health services can be priced through service effectiveness and service utility,and develops an economic incentive model with value pricing at its core based on the patient-centered incentive model for innovative healthcare services,including financing,payment,appraisal,and distribution,and puts forward feasible suggestions in the light of the needs and actuality of primary integrated services in China.Conclusion and Recommendation:The value-based pricing model for integrated health services serves as a theoretical foundation for the transformation of primary healthcare service functions and the enhancement of service dynamics,aligning with China's value-oriented service procurement strategy.This research contributes to the academic discourse by providing localized insights and a scholarly tone,contributing to the advancement of knowledge in the field.

Objective:Using primary care chronic disease management as a case,it aims to explore an economic incentive model for integrated primary healthcare services based on value pricing.Additionally,practical needs and implementation recommendations are proposed.Methods:With the help of the health technology assessment framework,it proposes that integrated health services can be priced through service effectiveness and service utility,and develops an economic incentive model with value pricing at its core based on the patient-centered incentive model for innovative healthcare services,including financing,payment,appraisal,and distribution,and puts forward feasible suggestions in the light of the needs and actuality of primary integrated services in China.Conclusion and Recommendation:The value-based pricing model for integrated health services serves as a theoretical foundation for the transformation of primary healthcare service functions and the enhancement of service dynamics,aligning with China's value-oriented service procurement strategy.This research contributes to the academic discourse by providing localized insights and a scholarly tone,contributing to the advancement of knowledge in the field.

Objective:Using primary care chronic disease management as a case,it aims to explore an economic incentive model for integrated primary healthcare services based on value pricing.Additionally,practical needs and implementation recommendations are proposed.Methods:With the help of the health technology assessment framework,it proposes that integrated health services can be priced through service effectiveness and service utility,and develops an economic incentive model with value pricing at its core based on the patient-centered incentive model for innovative healthcare services,including financing,payment,appraisal,and distribution,and puts forward feasible suggestions in the light of the needs and actuality of primary integrated services in China.Conclusion and Recommendation:The value-based pricing model for integrated health services serves as a theoretical foundation for the transformation of primary healthcare service functions and the enhancement of service dynamics,aligning with China's value-oriented service procurement strategy.This research contributes to the academic discourse by providing localized insights and a scholarly tone,contributing to the advancement of knowledge in the field.

Objective:Using primary care chronic disease management as a case,it aims to explore an economic incentive model for integrated primary healthcare services based on value pricing.Additionally,practical needs and implementation recommendations are proposed.Methods:With the help of the health technology assessment framework,it proposes that integrated health services can be priced through service effectiveness and service utility,and develops an economic incentive model with value pricing at its core based on the patient-centered incentive model for innovative healthcare services,including financing,payment,appraisal,and distribution,and puts forward feasible suggestions in the light of the needs and actuality of primary integrated services in China.Conclusion and Recommendation:The value-based pricing model for integrated health services serves as a theoretical foundation for the transformation of primary healthcare service functions and the enhancement of service dynamics,aligning with China's value-oriented service procurement strategy.This research contributes to the academic discourse by providing localized insights and a scholarly tone,contributing to the advancement of knowledge in the field.