OBJECTIVE To evaluate the cost-effectiveness of anlotinib combined with penpulimab versus sorafenib as first- line treatment for unresectable hepatocellular carcinoma （uHCC） from the perspective of China’s healthcare system. METHODS Based on data from the APOLLO study， a partitioned survival model was established with a 21-day model cycle to simulate patient survival status over 10 years under anlotinib combined with penpulimab regimen or sorafenib monotherapy. Quality-adjusted life year （QALY） was used as the core evaluation parameter to assess the incremental cost-effectiveness ratio （ICER） of different treatment regimens. Using 3 times China’s per capita gross domestic product （GDP） in 2024 （287 247 yuan/QALY） as the willingness-to-pay （WTP） threshold， cost-utility analysis was performed to evaluate the cost-effectiveness of the treatment regimens. Sensitivity analysis was conducted to validate the robustness of the baseline analysis conclusion. Scenario analysis was performed to consider the impact of anlotinib and penpulimab assistance programs on the results； the price reduction of penpulimab to ensure the cost-effectiveness of the combination regimen was examined under varying WTP thresholds （specifically， 1， 2， and 3 times China’s per capita GDP in 2024）. RESULTS The baseline analysis revealed that the ICER of anlotinib combined with penpulimab regimen relative to the sorafenib regimen was 338 611.20 yuan/QALY， which exceeded the WTP threshold set in this study. Univariate sensitivity analysis indicated that the utility value of progression free survival and penpulimab price significantly influenced the baseline analysis results. Probabilistic sensitivity analysis validated the robustness of the baseline results. The results of scenario analysis indicated that when considering the assistance programs for anlotinib and penpulimab， the obtained ICER values were all below the WTP threshold set at 3 times China’s per capita GDP in 2024. When the price of penpulimab was reduced by 58%， 35%， and 13%， the ICER values were below the WTP threshold， which was 1， 2 and 3 times the per capita GDP of China in 2024， respectively. CONCLUSIONS From the perspective of China’s healthcare system， anlotinib combined with penpulimab regimen for first-line treatment of uHCC lacks cost-effectiveness compared to sorafenib regimen. However， this conclusion would be reversed if the anlotinib and penpulimab assistance programs are taken into account or if the price of penpulimab is reduced by more than 13% and above.

OBJECTIVE To evaluate the cost-effectiveness of culmerciclib combined with fulvestrant as second-line treatment for patients with hormone receptor-positive（HR+）/human epidermal growth factor receptor 2-negative （HER2–） locally advanced or metastatic breast cancer， within the context of the Chinese healthcare system. METHODS A partitioned survival model was established based on the CULMATE-1 study， with a simulation time horizon set at 15 years and a cycle length of 28 days. The incremental cost-effectiveness ratio （ICER） of culmerciclib combined with fulvestrant versus fulvestrant monotherapy as second-line treatment for HR+/HER2– breast cancer was calculated. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the robustness of the model. Meanwhile， scenario analysis of culmerciclib price reduction was conducted； the required price reduction and price to reach the willingness-to-pay （WTP） threshold in this study were calculated. RESULTS The results of the base-case analysis indicated that， compared with the fulvestrant monotherapy regimen， culmerciclib combined with fulvestrant yielded an additional 0.823 quality-adjusted life year （QALY）， with a corresponding ICER of 371 696.26 yuan/QALY， which exceeded the WTP threshold （199 330 yuan/QALY）. The results of the univariate sensitivity analysis indicated that the cost of culmerciclib， the discount rate， the utility values for progression disease and progression free survival status were significant factors influencing the ICER； both the univariate sensitivity analysis and the probabilistic sensitivity analysis validated the robustness of the model results. Scenario analysis indicated that when the price of culmerciclib was reduced by 30%， 55% and 85% respectively， the corresponding ICER values fell below 3， 2， and 1 times China’s per capita GDP in 2025， with the probability of cost-effectiveness being 3.00%， 94.90%， 100%. When the cost of culmerciclib （60 mg） was reduced by 52.6% to 50.96 yuan， the ICER value met the WTP threshold established in this study. CONCLUSIONS When the WTP threshold is set at twice China’s per capita GDP in 2025， second-line treatment with culmerciclib combined with fulvestrant for HR+/HER2– locally advanced or metastatic breast cancer does not exhibit cost-effectiveness advantage over fulvestrant monotherapy. Therefore， a reasonable price reduction is required to alleviate the financial burden on patients.

OBJECTIVE To evaluate the cost-effectiveness of amivantamab combined with lazertinib （hereinafter referred to as “AL”） regimen as first-line treatment for EGFR -mutated advanced non-small cell lung cancer （NSCLC） from the perspective of China’s healthcare system. METHODS A partitioned survival model was established based on updated data from the MARIPOSA study， with a 10-year time horizon and 28-day cycles. The primary outcome index was quality adjusted life year （QALY）， and the willingness-to-pay （WTP） threshold was set at three times China’s per capita GDP in 2024 （287 247 yuan/QALY）. Cost-utility analysis was used to calculate the incremental cost-effectiveness ratio （ICER） of AL regimen versus osimertinib monotherapy regimen as first-line treatment for EGFR -mutated advanced NSCLC. One-way and probabilistic sensitivity analyses were performed to test model robustness. Scena rio analyses were conducted to explore the impact of utility values for different health states on the outcomes and determine the required price reductions of amivantamab and lazertinib to achieve cost-effectiveness. RESULTS Compared with the osimertinib monotherapy regimen， the ICER for the AL regimen as first-line treatment for advanced EGFR -mutated NSCLC was 2 062 096.15 yuan/QALY， significantly exceeding the WTP threshold established in this study. One-way sensitivity analysis revealed that the utility value of progression-free survival state and the price of amivantamab were the primary factors influencing the ICER. Probabilistic sensitivity analysis revealed that the AL regimen only became cost-effective when the WTP threshold was set at 2 050 000 yuan/QALY. Scenario analysis indicated that altering the utility value still rendered the AL regimen non-cost-effective. When amivantamab （350 mg） prices decreased by 80%， 85%， and 90% respectively， lazertinib （80 mg） prices would need to decrease by 95.97%， 40.63%， 5.29%， respectively. This would enable the AL regimen’s ICER to consistently fall within the WTP threshold established in this study. CONCLUSIONS At the WTP threshold established in this study， the AL regimen does not demonstrate cost-effectiveness for first-line treatment of advanced EGFR -mutated NSCLC compared to the osimertinib monotherapy regimen. Significant price reductions for both drugs would be required to alleviate the financial burden on patients.

OBJECTIVE To evaluate the cost-effectiveness of onradivir versus oseltamivir in the treatment of influenza A in adults from the perspective of the Chinese healthcare system. METHODS Based on data from a phase Ⅲ clinical trial （NCT04683406）， a decision tree model was constructed to simulate the efficacy and cost of using onradivir versus oseltamivir in treating adult patients with influenza A， with a cycle length of 5 days and a simulation period of 29 days. The two drug prices correspond to the median listing prices published by Yaozhi Network and the national negotiated prices. Patient characteristics and influenza utility values were derived from the phase Ⅲ clinical trial of onradivir， and medical costs and complication utility values were sourced from published literature. Quality-adjusted life year（QALY） was used as an effect indicator， and the incremental cost-effectiveness ratio（ICER） of onradivir versus oseltamivir was calculated， using China’s per capita disposable income in 2025 （43 377 yuan） as the willingness-to-pay （WTP） threshold to evaluate the cost-effectiveness of the results. One-way and probabilistic analyses were performed to verify the robustness of the results. RESULTS Compared with the oseltamivir regimen， the onradivir regimen yielded an incremental 0.000 67 QALY with direct medical cost savings of 12.41 yuan， thus being a dominant strategy. One-way sensitivity analysis showed that the utility values on day 15 of oseltamivir treatment， the incidence of influenza pneumonia in the oseltamivir group and the costs of the two drugs significantly affected the results. Probabilistic sensitivity analysis indicated that at the pre-specified WTP threshold， onradivir had a 70.6% probability of being cost-effective. CONCLUSIONS At a WTP threshold set at the 2025 per capita disposable income of China， compared with oseltamivir， onradivir can improve the health outcomes of adult patients with influenza A and reduce costs， demonstrating greater cost-effectiveness.

Objective:To compare the advantages and disadvantages and training costs of different training methods for microsurgical vascular anastomosis, and to provide a basis for establishing a systematic training model and improving surgeons microsurgical skills and clinical competence.Methods:Doctors came from various primary hospitals and exchange groups from foreign hospitals to China, and several groups of data statistics from 2018-2023 were randomly selected for this study. The microsurgical vascular anastomosis training lasted 10 days, including 1 day of theoretical study and 9 days of practical training. A total of 48 doctors were equally divided into group A (one-person operation), group B (two-person cooperation), and group C (two-person cooperation in the first four days and one-person operation in the last five days). The differences in anastomosis time and number of anastomoses between the groups were analysed by one-way ANOVA using the software GraphPad Prism 8.3.0, with P<0.05 indicating that there were statistically significant differences in the variable data. The cost of the three training methods was investigated, and a questionnaire survey of the trainees was conducted. Results:For all the three groups, the speed of anastomosis and the number of anastomoses increased with the course of training. The duration of single-vessel anastomosis was significantly different between groups A and B as well as between groups A and C at all time points except on day 1 (A1 d vs. B1 d, P=0.335; A1 d vs. C1 d, P=0.064; P<0.05 for all the other time points); groups B and C showed no significant differences on day 1 ( P=0.196) and day 3 ( P=0.115) but had significant differences on days 5, 7, and 9 (all P<0.05) in the duration of anastomosis. The number of anastomoses was not significantly different between A1 d and B1 d ( P=0.081), between A3 d and B3 d ( P=0.160), between B1 d and C1 d ( P=0.695), between B3 d and C3 d ( P=0.520), and between A1 d and C1 d ( P=0.123), with significant differences at the other time points (all P<0.05). The training costs were group A > group C > group B. The training questionnaire showed that the proportion of trainees who applied this technique in their daily work was 100.00% (48/48), the proportion of those who wished to participate in the training of this technique occasionally was 100.00% (48/48), the proportion of participants whose institutions had no relevant training conditions was 37.50% (18/48), the proportion of those whose institutions lacked necessary instruments and equipment was 35.42% (17/48), the proportion of those who had difficulties in access to laboratory animals was 68.75% (33/48), and the proportion of inability to carry out relevant training due to the lack of animal experimentation techniques such as anesthesia, preservation, and euthanasia was 91.67% (44/48), indicating that there is a great need for microsurgical vascular anastomosis training. Conclusions:The three training modes have their own advantages and disadvantages. The A mode is suitable for small-scale training. The B mode is suitable for training with adequate funds, a large number of personnel, and a high use frequency. The C mode is the best choice for microsurgical vascular anastomosis training, in which trainees can not only practice the whole vascular anastomosis process but also cooperative skills for anastomosis.

Objective To evaluate the cost-effectiveness of deucravacitinib in the treatment of moderate to severe plaque psoriasis from the perspective of the Chinese health system.Methods Based on POETYK PSO-1 study and related cost and utility data,a decision tree combined with Markov model was established.The model period was 10 years,and the output indicators of the model were cost and quality-adjusted life year(QALY).The evaluation index of the model was the incremental cost-effectiveness ratio(ICER).The willingness-to-pay threshold(WTP)was 3 times of China's per capita GDP in 2023.Sensitivity analysis was performed to evaluate the robustness of the model results.Results The incremental utility and incremental cost were 0.598QALYs and 130 677.51 yuan(RMB),respectively.The ICER of the two strategies was 218 487.11 yuan(RMB)per QALY gained,which was less than 3 times GDP per capita in 2023.Sensitivity analyses confirmed the robustness of the model.Conclusion Under the threshold of 3 times the GDP per capita in China,deucravacitinib is cost-effective in the treatment of moderate to severe plaque psoriasis.

BACKGROUND:Understanding the characteristics and influencing factors of the gut microbiota in athletes can help determine the optimal gut microbial composition for relevant sport events.Further investigation in this area could provide important insights for improving athletic performance and recovery as well as developing personalized nutrition prescriptions.OBJECTIVE:To summarize the characteristics of gut microbiota in athletes,and to elucidate the important factors influencing the gut microbiota characteristics of athletes from the perspectives of exercise training and dietary intake.METHODS:A literature search was conducted using the PubMed,ScienceDirect,CNKI,WanFang and VIP databases for publications from 2004 to 2024.The search terms included"microbiota,microbiome,athlete,exercise,training,diet,nutrition,dietary fiber,protein,ketogenic,fat"in English and Chinese.After excluding studies of poor quality and irrelevant content,a total of 65 articles were included for review and analysis.RESULTS AND CONCLUSION:(1)The gut microbiota of elite athletes differs from that of the general population,characterized by increased α-diversity,elevated Firmicutes/Bacteroidetes ratio,increased abundance of beneficial bacteria,and enrichment of functional pathways contributing to athletic performance.(2)The type of sport and training load are closely related to the species structure and functional expression of the gut microbiota in athletes.(3)The bidirectional communication between the host and gut microbiota mediated by metabolites is an important mechanism by which exercise influences the gut microbiota.(4)Phase training typically induces adaptive changes in the gut microbiota,and alterations in the structure or function of the microbiota have lasting effects.(5)The type,quantity,and combination of macronutrients intake can significantly influence the structure and function of the gut microbiota,and interact synergistically or antagonistically with exercise training.(6)In the future,it is important to continue the exploration of the gut microbiota in athletes,clarify causal relationships,and establish new targets for exercise training interventions.

OBJECTIVE To provide help for further exploring the mechanism of action of traditional Chinese herb by constructing a complex network of traditional Chinese herb-gene-protein,optimizing the mining method of potential associated genes of traditional Chinese herb and improving the mining efficiency of traditional Chinese herb system biology information.METHODS A graph neural network model HERBGAT with an attention mechanism was proposed.A small amount of traditional Chinese herb-related gene data in the public data platform was used as input,and deep mining was performed in the traditional Chinese herb-gene-protein complex net-work to output potential traditional Chinese herb-related genes.The prediction results were analyzed by disease association analysis and KEGG signaling pathway analysis on the bioinformatics platform to clarify their mechanism of action,and the prediction results were verified by the literature retrieval platform.RESULTS The training results showed that the average prediction accuracy of the HERB-GAT model could reach 94%.Compared with the other two advanced complex network mining methods,HERBGAT showed better per-formance in the three indicators of ACC,AUC and AUPR.In the literature verification stage,the model prediction results were verified by TCM clinical literature and modern pharmacology literature,showing the good effect of HERBGAT in practical application.At the end of this paper,taking the HERBGAT model and the improved EMOGI model to explore the mechanism of action of Pinellia ternata in treating lung cancer as an example,199 potential associated genes of Pinellia ternata in treating lung cancer were found,and these potential associated genes were preliminarily analyzed and discussed with the help of bioinformatics methods.CONCLUSION The HERBGAT model can effectively mine potential traditional Chinese herb-associated genes,improve the mining efficiency of traditional Chinese herb-gene-protein complex networks,provide new ideas and references for the optimization of traditional Chinese herb system biology information mining methods,and provide data basis and experimental direction for exploring the mechanism of action of tradi-tional Chinese herb.

OBJECTIVE To investigate the deglycosylation metabolism of dioscin in vivo and the changes of its anti-tumor activi-ty of its deglycosylated metabolites.METHODS An LC-MS/MS analysis method for simultaneous determination of dioscin and its deglycosylation metabolites was established to study the cumulative excretion amount of dioscin and its deglycosylated metabolites in rat feces after oral administration.To mimic its deglycosylation metabolism,HPLC method was applied to investigate the time-dependent changes in the prototype components and metabolites of dioscin after incubation in artificial gastric juice.Solid-phase extraction tech-nology was employed to isolate the product of dioscin following hydrolysis by artificial gastric juice.The cytotoxic effects of this product on human colon cancer cells HCT-116 were assessed using the CCK-8 assay across different hydrolysis time periods.Concurrently,the enzymatic activities of caspase-3 and caspase-9,along with the expression levels of cytochrome C,were measured to elucidate the impact of dioscin post-hydrolysis on the cytotoxicity against HCT-116 cells.RESULTS Dioscin and its series of deglycosylated me-tabolites were detected in rat feces,revealing no significant differences in the cumulative excretion amounts of Polyphyllin Ⅴ and Pro-genin Ⅱ.Dioscin was shown to generate a range of deglycosylated metabolites in artificial gastric juice.Furthermore,dioscin and its deglycosylated metabolites inhibited the proliferation of HCT-116 cells,induced morphological changes,and increased the enzymatic activities of caspase-3 and caspase-9,as well as cytochrome C expression.However,it was observed that the antitumor activity of the deglycosylated metabolites diminished with prolonged hydrolysis time.CONCLUSION The deglycosylation metabolism of dioscin sig-nificantly attenuates its inhibitory effect on the proliferation of HCT-116 cells.Suppressing the acid-mediated or gut microbiota-medi-ated deglycosylation metabolism may be a promising strategy to preserve its antitumor activity.

Objective:To analyze the impact of wound closure in knee flexion versus extension on postoperative outcomes after total knee arthroplasty (TKA).Methods:Randomized controlled trials (RCTs) comparing the effects of knee flexion versus extension wound closure on TKA outcomes were retrieved from databases including CNKI, WanFang Data, Chinese Medical Journal Full-text Database, PubMed, Medline, Cochrane Library, and Embase, from inception to October 1, 2024. Outcome measures include knee range of motion (ROM), Knee Society score (KSS), visual analogue scale (VAS), and incidence of postoperative complications at different time points. Meta-analysis was performed using Stata 18.0. The methodological quality of included RCTs was assessed using the modified Jadad scale. A fixed-effects model was applied when heterogeneity was low, while a random-effects model was used when heterogeneity was high.Results:A total of 467 patients from 7 RCTs were included (233 in flexion group, 234 in extension group). The mean age was 66.4 years in the flexion group and 66.7 years in the extension group, with a follow-up ranging from 1 to 12 months. All studies were of high quality. The meta-analysis revealed that the flexion group had significantly greater knee ROM at 1 month [ WMD=3.72, 95% CI(3.12, 4.33), P<0.001] and 3 months [ WMD=5.31, 95% CI(0.79, 9.84), P=0.020] postoperatively compared to the extension group. At 6 months postoperatively, the flexion group showed significantly higher KSS [ WMD=-1.25, 95% CI(-1.51, -0.99), P<0.001]. No significant differences were found in ROM at 6 months [ WMD=0.89, 95% CI(-0.99, 2.77), P=0.350], VAS at 3 months [ WMD=-0.28, 95% CI(-1.59, -0.03), P=0.075], or complication rates [ RD=0.03, 95% CI(-0.01,0.07), P=0.198]. Conclusion:Wound closure in knee flexion can improve early knee range of motion within 3 months and functional outcomes at 6 months after TKA.