BACKGROUND:Psoralen has a strong anti-osteoporotic activity and may have a restorative effect on chemotherapy-induced osteoporosis. OBJECTIVE:To explore the restorative effect of psoralen on the osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide and its mechanism. METHODS:C57BL/6 mouse bone marrow mesenchymal stem cells were isolated and cultured.Effect of psoralen on viability of bone marrow mesenchymal stem cells was detected by MTT assay.Osteogenic induction combined with alkaline phosphatase staining was used to determine the optimal dose of psoralen to restore the osteogenic differentiation of bone marrow mesenchymal stem cells inhibited by cyclophosphamide.The mRNA expression levels of Runx2,alkaline phosphatase,Osteocalcin,osteoprotegerin,and Wnt/β-catenin signaling pathway-related genes Wnt1,Wnt4,Wnt10b,β-catenin,and c-MYC were measured by RT-qPCR at different time points under the intervention with psoralen.The protein expression of osteogenic specific transcription factor Runx2 and Wnt/β-catenin signaling pathway related genes Active β-catenin,DKK1,c-MYC,and Cyclin D1 was determined by western blot assay at different time points under the intervention with psoralen. RESULTS AND CONCLUSION:(1)There was no significant effect of different concentrations of psoralen on the viability of bone marrow mesenchymal stem cells.The best recovery of the inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells caused by cyclophosphamide was under the intervention of psoralen at a concentration of 200 μmol/L.(2)Psoralen reversed the reduction in osteogenic differentiation marker genes Runx2,alkaline phosphatase,Osteocalcin and osteoprotegerin mRNA expression and Runx2 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(3)Psoralen reversed the decrease in Wnt/β-catenin pathway-related genes Wnt4,β-catenin,c-MYC mRNA and Active β-catenin,c-MYC,and Cyclin D1 protein expression and the increase in DKK1 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(4)The results showed that cyclophosphamide inhibited osteogenic differentiation of bone marrow mesenchymal stem cells in mice,and psoralen had a restorative effect on it.The best intervention effect was achieved at a concentration of 200 μmol/L psoralen,and this protective effect might be related to the activation of Wnt4/β-catenin signaling pathway by psoralen.

OBJECTIVE To evaluate the cost-effectiveness of dapagliflozin and empagliflozin in the treatment of type 2 diabetic kidney disease from the perspective of healthcare system in China. METHODS Based on the data from the two multicenter clinical trials， DECLARE-TIMI 58 and EMPA-REG OUTCOME， a Markov model was constructed according to the urinary albumin-to-creatinine ratio （UACR） of the patients with type 2 diabetic kidney disease with a cycle of 1 year， simulating until 99% of patients died. The model outputs were total costs and quality-adjusted life year （QALY）. The cost-effectiveness of the two treatment regimens was assessed by comparing their incremental cost-effectiveness ratio （ICER） and the willingness-to-pay threshold （WTP，set at three times China’s 2023 per capita gross domestic product， i.e.， 268 074 yuan/QALY）. Additionally， oneway sensitivity analysis and probabilistic sensitivity analysis were performed to test the robustness of the base analysis results. RESULTS Compared with dapagliflozin， the ICER for empagliflozin regimen was 44 334.82 yuan/QALY， which was below the WTP ， indicating its cost-effectiveness. The results of the oneway sensitivity analysis indicated that the incidence of non-fatal myocardial infarction in both groups and the utility values associated with the microalbuminuria state had the most significant impact on the outcomes， but did not change the base-case conclusion. The probabilistic sensitivity analysis indicated that the results of the base-case analysis were robust. CONCLUSIONS With a WTP of three times China’s per capita gross domestic product in 2023， empagliflozin is more cost-effective than dapagliflozin in treating type 2 diabetic kidney disease.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Objective To observe the effects of Huatan Quyu Decoction on cognitive function and the expressions of GABA and VILIP-1 in brain tissue of rats with cerebral small vessel disease;To discuss its mechanism for treatment on cerebral small vessel disease.Methods Totally 48 male SD rats were randomly divided into blank group,model group,Huatan Quyu Decoction low-and high-dosage groups,with 12 rats in each group.Except for the blank group,a rat model of cerebral small vessel disease was prepared by in vitro injection of homologous microemboli.Huatan Quyu Decoction low-and high-dosage groups were given Huatan Quyu Decoction 1.25 and 2.5 g/kg by gavage,the blank group and model group were gavage with equal amounts of distilled water for 28 consecutive days.Morris water maze experiment was conducted on day 1,7,14,and 28 after administration to evaluate the learning and memory abilities of rats,HE staining was used to observe pathological changes in hippocampal tissue,and immunohistochemical staining was used to detect the expressions of GABA and VILIP-1 proteins in brain tissue.Results Compared with the blank group,the escape latency of Morris water maze experiment in model group significantly prolonged(P<0.05),and the number of crossing platforms was significantly reduced(P<0.05);the arrangement of hippocampal tissue cells was disordered,gaps widen,and nuclei atrophy and necrosis,the GABA expression in brain tissue significantly decreased(P<0.05),while the VILIP-1 expression significantly increased(P<0.05).Compared with the model group,the escape latency of Morris water maze experiment in the Huatan Quyu Decoction low-and high-dosage groups significantly shortened(P<0.05)on day 7,14,and 28 of administration,and the number of crossing platforms significantly increased(P<0.05),GABA expression significantly increased(P<0.05),while VILIP-1 expression significantly decreased(P<0.05).Compared with the Huatan Quyu Decoction low-dosage group,the escape latency of Morris water maze experiment in Huatan Quyu Decoction high-dosage group decreased at various time points,and the number of crossing platforms increase,the pathological damage of hippocampal tissue was reduced,the expression of GABA in brain tissue increased,and the expression of VILIP-1 decreased,with statistical significance(P<0.05).Conclusion Huatan Quyu Decoction can increase the expression of GABA in brain tissue and inhibit the expression of VILIP-1,thereby improve the cognitive function of rats with cerebrovascular disease.

Objective To propose a heart sound segmentation method based on multi-feature fusion network. Methods Data were obtained from the CinC/PhysioNet 2016 Challenge dataset (a total of 3 153 recordings from 764 patients, about 91.93% of whom were male, with an average age of 30.36 years). Firstly the features were extracted in time domain and time-frequency domain respectively, and reduced redundant features by feature dimensionality reduction. Then, we selected optimal features separately from the two feature spaces that performed best through feature selection. Next, the multi-feature fusion was completed through multi-scale dilated convolution, cooperative fusion, and channel attention mechanism. Finally, the fused features were fed into a bidirectional gated recurrent unit (BiGRU) network to heart sound segmentation results. Results The proposed method achieved precision, recall and F1 score of 96.70%, 96.99%, and 96.84% respectively. Conclusion The multi-feature fusion network proposed in this study has better heart sound segmentation performance, which can provide high-accuracy heart sound segmentation technology support for the design of automatic analysis of heart diseases based on heart sounds.

OBJECTIVE To provide a reference for the improvement of pharmacoeconomic evaluation and health economic decision-making in China. METHODS From the perspective of China’s healthcare system， a three-state partitioned survival model was constructed based on the BECOME study， the quality-adjusted life year （QALY） and equal value of life-year gained（evLYG） were used as the health gain measures respectively， and the cost-utility analysis was used to evaluate the cost-effectiveness of bevacizumab combined with chemotherapy regimen versus chemotherapy alone in the first-line treatment of RAS-mutant metastatic colorectal cancer （mCRC）. The cycle length was 2 weeks， the time horizon was the patients’ lifetime， the discount rate was 5%， and the willingness-to-pay threshold was 1 to 3 times China’s gross domestic product per capita in 2023 （89 358-268 074 yuan）. One-way sensitivity analysis and probabilistic sensitivity analysis were used to assess the robustness of the results. RESULTS Compared to the chemotherapy alone， the incremental cost-effectiveness ratio （ICER） of the bevacizumab combined with chemotherapy regimen was calculated to be 330 311.33 yuan/QALY based on QALY， which exceeded the willingness-to-pay threshold （268 074 yuan）. However， when the ICER was calculated based on evLYG， it was determined to be 254 085.64 yuan/evLYG， which fell below the willingness-to-pay threshold （268 074 yuan）. The results of the one-way sensitivity analysis showed that the price of bevacizumab had the greatest impact on the ICER value. The results of the probabilistic sensitivity analysis showed that the probability of the bevacizumab combined with chemotherapy regimen being more cost-effective was approximately 3% when assessed by QALY； the probability of the regimen being more cost-effective rose to 56% when assessed by evLYG. CONCLUSIONS When evaluating the cost-effectiveness of interventions for RAS-mutant mCRC， ICER values based on evLYG may provide a fairer measure compared to ICER values calculated by QALY. It is recommended that when pharmacoeconomic evaluations are conducted for special populations， both QALY and evLYG can be used as health outcome indexes for evaluation to achieve a better allocation of healthcare resources and improve the fairness of decision-making.

Objective:To carry out a study on the cost analysis of the clinical use of Artificial Intelligence-assisted Diagnosis Technology for Coronary CT Angiography(CCTA-AI)to explore the cost differences and cost effects of Coronary CT Angiography(CCTA)examinations before and after the introduction of Artificial Intelligence(AI),and analyze the impact of the application of AI technology on the high-quality development of public hospitals.Methods:The operation cost method was used to measure the changes in the cost and efficiency of CCTA examinations before and after the application of AI technology in five sample hospitals in Beijing,and diagnostic accuracy was used as the effect value to calculate the cost effect of CCTA-AI diagnosis versus CCTA-manual diagnosis,and to analyze the main factors affecting the unit cost.Results:The average cost of examination in 5 sample hospitals after the application of AI-assisted diagnosis system was 1 074.90 yuan,and 1 266.61 yuan before the application,with a large difference between institutions.The cost-effectiveness analysis based on diagnostic accuracy showed that the AI group had an absolute advantage over the manual group,with a cost of 1 074 900 yuan for the AI group and an effectiveness of 855.05 persons,and a cost of 1 266 610 yuan for the physician group,with an effectiveness of 815.07 persons for the high-year-end physician group,and an effectiveness of 793.40 persons for the low-year-end physician group;0.46 man-hours could be saved for each patient examined;the unit cost of CCTA examination was affected by a number of factors,among which"the number of annual examinations"and"the number of CT units involved in CCTA examination"had the greatest influence on the unit cost of CCTA examination.Conclusion:The application of AI-assisted diagnostic technology can promote the improvement of quality and efficiency in public hospitals in a certain extent,and help optimize the overall distribution of medical resources at the system level.In the future,the cost analysis of AI technology should be further strengthened to comprehensively assess its actual contribution to the healthcare system.

Objective:To carry out a study on the cost analysis of the clinical use of Artificial Intelligence-assisted Diagnosis Technology for Coronary CT Angiography(CCTA-AI)to explore the cost differences and cost effects of Coronary CT Angiography(CCTA)examinations before and after the introduction of Artificial Intelligence(AI),and analyze the impact of the application of AI technology on the high-quality development of public hospitals.Methods:The operation cost method was used to measure the changes in the cost and efficiency of CCTA examinations before and after the application of AI technology in five sample hospitals in Beijing,and diagnostic accuracy was used as the effect value to calculate the cost effect of CCTA-AI diagnosis versus CCTA-manual diagnosis,and to analyze the main factors affecting the unit cost.Results:The average cost of examination in 5 sample hospitals after the application of AI-assisted diagnosis system was 1 074.90 yuan,and 1 266.61 yuan before the application,with a large difference between institutions.The cost-effectiveness analysis based on diagnostic accuracy showed that the AI group had an absolute advantage over the manual group,with a cost of 1 074 900 yuan for the AI group and an effectiveness of 855.05 persons,and a cost of 1 266 610 yuan for the physician group,with an effectiveness of 815.07 persons for the high-year-end physician group,and an effectiveness of 793.40 persons for the low-year-end physician group;0.46 man-hours could be saved for each patient examined;the unit cost of CCTA examination was affected by a number of factors,among which"the number of annual examinations"and"the number of CT units involved in CCTA examination"had the greatest influence on the unit cost of CCTA examination.Conclusion:The application of AI-assisted diagnostic technology can promote the improvement of quality and efficiency in public hospitals in a certain extent,and help optimize the overall distribution of medical resources at the system level.In the future,the cost analysis of AI technology should be further strengthened to comprehensively assess its actual contribution to the healthcare system.

Objective:To carry out a study on the cost analysis of the clinical use of Artificial Intelligence-assisted Diagnosis Technology for Coronary CT Angiography(CCTA-AI)to explore the cost differences and cost effects of Coronary CT Angiography(CCTA)examinations before and after the introduction of Artificial Intelligence(AI),and analyze the impact of the application of AI technology on the high-quality development of public hospitals.Methods:The operation cost method was used to measure the changes in the cost and efficiency of CCTA examinations before and after the application of AI technology in five sample hospitals in Beijing,and diagnostic accuracy was used as the effect value to calculate the cost effect of CCTA-AI diagnosis versus CCTA-manual diagnosis,and to analyze the main factors affecting the unit cost.Results:The average cost of examination in 5 sample hospitals after the application of AI-assisted diagnosis system was 1 074.90 yuan,and 1 266.61 yuan before the application,with a large difference between institutions.The cost-effectiveness analysis based on diagnostic accuracy showed that the AI group had an absolute advantage over the manual group,with a cost of 1 074 900 yuan for the AI group and an effectiveness of 855.05 persons,and a cost of 1 266 610 yuan for the physician group,with an effectiveness of 815.07 persons for the high-year-end physician group,and an effectiveness of 793.40 persons for the low-year-end physician group;0.46 man-hours could be saved for each patient examined;the unit cost of CCTA examination was affected by a number of factors,among which"the number of annual examinations"and"the number of CT units involved in CCTA examination"had the greatest influence on the unit cost of CCTA examination.Conclusion:The application of AI-assisted diagnostic technology can promote the improvement of quality and efficiency in public hospitals in a certain extent,and help optimize the overall distribution of medical resources at the system level.In the future,the cost analysis of AI technology should be further strengthened to comprehensively assess its actual contribution to the healthcare system.

Objective:To carry out a study on the cost analysis of the clinical use of Artificial Intelligence-assisted Diagnosis Technology for Coronary CT Angiography(CCTA-AI)to explore the cost differences and cost effects of Coronary CT Angiography(CCTA)examinations before and after the introduction of Artificial Intelligence(AI),and analyze the impact of the application of AI technology on the high-quality development of public hospitals.Methods:The operation cost method was used to measure the changes in the cost and efficiency of CCTA examinations before and after the application of AI technology in five sample hospitals in Beijing,and diagnostic accuracy was used as the effect value to calculate the cost effect of CCTA-AI diagnosis versus CCTA-manual diagnosis,and to analyze the main factors affecting the unit cost.Results:The average cost of examination in 5 sample hospitals after the application of AI-assisted diagnosis system was 1 074.90 yuan,and 1 266.61 yuan before the application,with a large difference between institutions.The cost-effectiveness analysis based on diagnostic accuracy showed that the AI group had an absolute advantage over the manual group,with a cost of 1 074 900 yuan for the AI group and an effectiveness of 855.05 persons,and a cost of 1 266 610 yuan for the physician group,with an effectiveness of 815.07 persons for the high-year-end physician group,and an effectiveness of 793.40 persons for the low-year-end physician group;0.46 man-hours could be saved for each patient examined;the unit cost of CCTA examination was affected by a number of factors,among which"the number of annual examinations"and"the number of CT units involved in CCTA examination"had the greatest influence on the unit cost of CCTA examination.Conclusion:The application of AI-assisted diagnostic technology can promote the improvement of quality and efficiency in public hospitals in a certain extent,and help optimize the overall distribution of medical resources at the system level.In the future,the cost analysis of AI technology should be further strengthened to comprehensively assess its actual contribution to the healthcare system.