OBJECTIVE To evaluate the efficacy， safety and economics of calcium channel modulators in the treatment of diabetic peripheral neuropathic pain （DPNP）， and provide evidence-based evidence for clinical drug selection and decision-making. METHODS PubMed， Embase， Cochrane Library， CNKI， Wanfang data， VIP net， CBM and official websites of foreign health technology assessment （HTA） institutions were systematically searched to collect HTA reports， systematic review/meta-analyses， and pharmacoeconomic studies of pregabalin， gabapentin， crisugabalin， and mirogabalin for the treatment of DPNP. The timeframe for all searches was from the inception to June 2024. After data extraction and quality assessment， the results of the included studies were analyzed descriptively. RESULTS A total of 16 articles were included， involving 1 HTA report， 7 systematic reviews/meta- analyses， and 8 pharmacoeconomic studies. No studies on crisugabalin were retrieved. Compared with placebo， both pregabalin and mirogabalin reduced end point pain scores and increased the proportion of patients with ≥30% and/or ≥50% reduction in pain scores. Pregabalin also improved patient global impression of change （PGIC）. Gabapentin was similar to placebo in reducing end point pain scores and increasing the proportion of patients with ≥30% and/or ≥50% reduction in pain scores， but gabapentin improved PGIC of patients. Compared with pregabalin， mirogabalin was more effective in the treatment of pain. The safety of pregabalin and mirogabalin was similar， and compared with placebo， both pregabalin and mirogabalin increased the risk of common adverse reactions such as dizziness and somnolence. The safety of gabapentin was similar to placebo and duloxetine. Compared with duloxetine， pregabalin and gabapentin were not cost-effective. Compared with gabapentin， pregabalin was cost-effective. Mirogabalin was cost-effective， as compared with placebo and pregabalin. CONCLUSIONS Pregabalin and mirogabalin are effective in the treatment of DPNP， the efficacy of mirogabalin is better than pregabalin， and the safety is similar between them. The economic conclusions vary from country to country， pending a pharmacoeconomic study based on our population.

OBJECTIVE To evaluate the cost-utility of benmelstobart combined with anlotinib and chemotherapy as first-line treatment for extensive-stage small cell lung cancer （ES-SCLC） from the perspective of China’s healthcare system. METHODS Based on the data from the ETER 701 study， a partitioned survival model was constructed with a cycle of 3 weeks to simulate the total cost， quality-adjusted life years （QALY）， and incremental cost-effectiveness ratio （ICER） over 10 years for patients with ES- SCLC treated with benmelstobart plus anlotinib and chemotherapy， or chemotherapy alone. One-way sensitivity analysis and probability sensitivity analysis were performed to verify the robustness of the simulation results. The willingness-to-pay （WTP） threshold was set at 3 times the per capita gross domestic product （GDP） of China in 2023， which amounted to 268 074 yuan/QALY. RESULTS Compared with chemotherapy alone， benmelstobart combined with anlotinib and chemotherapy gained 0.438 QALY more at the cost of 403 505.55 yuan more， with an ICER of 922 031.37 yuan/QALY， which was higher than the WTP threshold set in this study. One-way sensitivity analysis showed that benmelstobart’s cost and utility value of the progression-free survival state had a greater impact on the ICER value； probabilistic sensitivity analysis confirmed the robustness of the model； only when the price of benmelstobart was reduced by 75.4%， the combined regimen would be cost-effective. CONCLUSIONS The first-line treatment of ES-SCLC with benmelstobart combined with anlotinib and chemotherapy is not cost-effective from the perspective of China’s healthcare system at present.

OBJECTIVE To evaluate the cost-effectiveness of capecitabine metronomic chemotherapy combined with aromatase inhibitor （AI） versus AI monotherapy as first-line treatment for hormone receptor-positive （HR+）/human epidermal growth factor receptor 2-negative （HER2－） metastatic breast cancer， thereby providing evidence-based support for clinical therapeutic decision- making and healthcare policy formulation. METHODS Based on the MECCA trial， a partitioned survival model was constructed using a 4-week cycle length to simulate outcomes over patients’ lifetime. The model outputs included total costs， quality-adjusted life year （QALY）， and incremental cost-effectiveness ratio （ICER）. Sensitivity analyses were performed to validate the robustness of base-case results， while scenario analyses examined the cost-effectiveness of both treatment strategies under 10-year， 20-year， and lifetime time horizons. RESULTS With the willingness-to-pay （WTP） threshold set at 1 times China’s 2024 per capita gross domestic product （GDP） （95 749 yuan/QALY）， patients receiving capecitabine metronomic chemotherapy combined with AI regimen gained incremental utility （0.66 QALYs） while incurring higher costs， with ICER of 27 684.85 yuan/QALY. Results of the one-way sensitivity analysis showed that factors with significant impacts on ICER included the cost discount rate， drug costs of the capecitabine metronomic chemotherapy combined with AI group， utility value in the progression-free survival state， follow-up costs， and treatment costs in the subsequent stablephase. Probabilistic sensitivity analysis indicated that when the WTP threshold ≥49 250 yuan/QALY， the capecitabine metronomic chemotherapy combined with AI regimen had a 100% probability of being cost-effective. Scenario analysis results demonstrated that capecitabine metronomic chemotherapy combined with AI regimen was more cost-effective than the AI alone regimen across 10-year， 20-year， and lifetime study horizons. CONCLUSIONS Under the premise that the WTP threshold is set at 1 times China’s per capita GDP in 2024， capecitabine metronomic chemotherapy combined with AI regimen is more cost-effective than the AI alone regimen as the first-line treatment for HR+/HER2－ metastatic breast cancer.

OBJECTIVE To evaluate the cost-effectiveness of sacituzumab tirumotecan （ST） versus chemotherapy treatment physician’s choice （TPC） as second-line and later-line treatment for metastatic triple-negative breast cancer （mTNBC） from the perspective of China’s healthcare system. METHODS A partitioned survival model was constructed based on the OptiTROP-Breast 01 trial， with a cycle length of 4 weeks and a time horizon of 10 years， applying a 5% discount rate. Quality adjusted life year （QALY） and costs were used as outcome measures， and the incremental cost-effectiveness ratio （ICER） of ST versus TPC for second-line and later-line treatment of mTNBC was calculated. Sensitivity analyses were conducted to validate the robustness of the base-case results. RESULTS At a willingness-to-pay threshold （WTP） of 3 times China’s 2024 per capita gross domestic product （GDP） （287 247 yuan/QALY）， patients receiving ST gained incremental utility （0.42 QALY） at a higher cost， yielding an ICER of 205 562.07 yuan/QALY， which was lower than WTP， indicating that ST was more cost-effective compared to TPC. One-way sensitivity analysis revealed that key factors influencing the ICER included the utility value of progression-free survival and the price of ST. Probabilistic sensitivity analysis and scenario analysis showed that the base-case results were robust. CONCLUSIONS From the perspective of China’s healthcare system， at a WTP of 3 times China’s per capita GDP， ST is more cost-effective than TPC as second-line and later-line treatment for mTNBC.

Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.

OBJECTIVE To construct ensemble learning models for predicting high-use days of budesonide based on meteorological factors， thereby providing reference for hospital pharmacy management. METHODS Meteorological data for 2024 and outpatient budesonide usage data from the jurisdiction of Sanming Hospital of Integrated Traditional Chinese and Western Medicine were collected. High-use days were defined as the 75th percentile of outpatient budesonide usage， and a corresponding dataset was established. The prediction task was formulated as a classification problem， and three ensemble learning models were developed： Random Forest， Extreme Gradient Boosting （XGBoost）， and Histogram-based Gradient Boosting Classifier. Model performance was evaluated using accuracy， precision， recall， F1-score， and log-loss. Model interpretability was analyzed using Shapley Additive Explanations （SHAP）. RESULTS The Histogram-based Gradient Boosting Classifier achieved the best performance （accuracy＝0.75， F1-score＝0.48）， followed by XGBoost （accuracy＝0.74， F1-score＝0.43） and Random Forest （accuracy＝0.72， F1-score＝0.22）. SHAP results suggested that the prediction results of the last two models have the highest correction. CONCLUSIONS Ensemble learning models can effectively predict high-use days of budesonide， with the Histogram- based Gradient Boosting Classifier demonstrating the best predictive performance. Low temperature， high humidity， and low atmospheric pressure show significant positive impacts on the prediction of daily budesonide usage.

Objective:To explore the metabolic basis and related molecular mechanism of oral squamous cell carcinoma(OSCC)path-ogenesis.Methods:20 Chinese hamsters were divided into 2 groups(n=10).OSCC models were induced by dimethylbenzanthracene(DMBA)in 10 of the animals and the other 10 were used as the controls.LC-MS chromatography-mass spectrometry was used to iden-tify the metabolites in the buccal pouch,and multidimensional statistical analysis of the metabolites was performed with the orthogonal partial least squares discriminant analysis model.Variable Importance for the Projection(VIP)＞1 and P＜0.05 were used as the criteria to screen the differential metabolites between the 2 groups.KEGG pathway annotation and enrichment analysis for the metabolites were performed to screen the significantly differential pathways.Results:The hamster cheek pouches painted with 0.5％DMBA for 18 weeks were diffused with leukoplakia and loaded obvious papillary protrusions,which were diagnosed as OSCC by pathological examination.Lipids and lipid-like molecules were the main differential metabolites.Reprogramming of unsaturated fatty acid biosynthesis,cholesterol accumulation,enhanced catabolism of tryptophan,up-regulation of aspartate,increased synthesis of pyrimidine and purine,etc.were important metabolic features in the occurrence and development of OSCC.Conclusion:Molecular intervention targeting the related met-abolic pathways is expected to inhibit OSCC pathogenesis and progression.

OBJECTIVE: Anemoside B4 (AB4), the most abundant triterpenoidal saponin isolated from Pulsatilla chinensis, inhibited influenza virus FM1 or Klebsiella pneumoniae-induced pneumonia. However, the anti-SARS-CoV-2 effect of AB4 has not been unraveled. Therefore, this study aimed to determine the antiviral activity and potential mechanism of AB4 in inhibiting human coronavirus SARS-CoV-2 in vivo and in vitro. METHODS: The cytotoxicity of AB4 was evaluated using the Cell Counting Kit-8 (CCK8) assay. SARS-CoV-2 infected HEK293T, HPAEpiC, and Vero E6 cells were used for in vitro assays. The antiviral effect of AB4 in vivo was evaluated by SARS-CoV-2-infected hACE2-IRES-luc transgenic mouse model. Furthermore, label-free quantitative proteomics and bioinformatic analysis were performed to explore the potential antiviral mechanism of action of AB4. Type I IFN signaling-associated proteins were assessed using Western blotting or immumohistochemical staining. RESULTS: The data showed that AB4 reduced the propagation of SARS-CoV-2 along with the decreased Nucleocapsid protein (N), Spike protein (S), and 3C-like protease (3CLpro) in HEK293T cells. In vivo antiviral activity data revealed that AB4 inhibited viral replication and relieved pneumonia in a SARS-CoV-2 infected mouse model. We further disclosed that the antiviral activity of AB4 was associated with the enhanced interferon (IFN)-β response via the activation of retinoic acid-inducible gene I (RIG-1) like receptor (RLP) pathways. Additionally, label-free quantitative proteomic analyses discovered that 17 proteins were significantly altered by AB4 in the SARS-CoV-2 coronavirus infections cells. These proteins mainly clustered in RNA metabolism. CONCLUSION Our results indicated that AB4 inhibited SARS-CoV-2 replication through the RLR pathways and moderated the RNA metabolism, suggesting that it would be a potential lead compound for the development of anti-SARS-CoV-2 drugs.

OBJECTIVE To assess the long-term cost-effectiveness of five glucagon-like peptide-1 receptor agonists （GLP- 1RAs） in the treatment of poorly controlled type 2 diabetes mellitus （T2DM） treated with metformin. METHODS Baseline data from patients in previously published meta-analysis and included randomized controlled trials （RCTs） were extracted to predict survival， long-term efficacy， and costs for each group using the United Kingdom prospective diabetes study outcome model 2.1. The cost-effectiveness of 5 GLP-1RAs （liraglutide， lixisenatide， exenatide， dulaglutide， and semaglutide） was analyzed by cost- utility analysis. Sensitivity analysis and scenario analysis were also performed to verify the uncertainty of basic analysis results. RESULTS A total of 21 RCTs with 6 796 patients were included. Survival analysis curves showed the superiority of semaglutide in reducing the risk of death from cardiovascular disease and dulaglutide in reducing the risk of all-cause mortality over other GLP- 1RAs. The cost-utility analysis showed that the five drugs were economically superior to inferior in the order of lixisenatide， semaglutide， exenatide， dulaglutide， and liraglutide； one-way and probabilistic sensitivity analyses indicated that the results were robust. The scenario analysis results indicated that the price of semaglutide should decrease by at least 54.64% to 369.21 yuan， which is cost-effectiveness compared to lixisenatide. CONCLUSIONS For T2DM patients in China with poor glycemic control after treatment with metformin， lixisenatide and semaglutide may be considered as the preferred regimen.

OBJECTIVE To evaluate the cost-effectiveness of tislelizumab combined with chemotherapy as first-line treatment for locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. METHODS The data of RATIONALE-305 study and related literature were used to establish a partitioned survival model from the perspective of China’s health system. The cycle was 3 weeks， the simulation time was set as 10 years， and the discount rate was 5%. The quality-adjusted life years （QALYs） were used as the health outcome indicator to evaluate the cost-effectiveness of tislelizumab combined with chemotherapy versus placebo combined with chemotherapy as first-line treatment for locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma， and one-way sensitivity analysis and probabilistic sensitivity analysis were also conducted. RESULTS The base analysis showed that the patients received more 0.268 QALYs with tislelizumab plus chemotherapy， compared with placebo plus chemotherapy， but the cost increased by 70 404.81 yuan with an incremental cost- effectiveness ratio （ICER） of 262 431.62 yuan/QALY， which was less than three times China’s gross domestic product （GDP） per capita in 2023 as the willingness-to-pay （WTP） threshold （268 074 yuan/QALY）. One-way sensitivity analysis showed that the efficacy value of progress free survive and the price of tislelizumab had a greater impact on the ICER value. The results of probability sensitivity analysis showed that when the WTP threshold was 3 times China’s GDP per capita in 2023， the probability of tislelizumab being cost-effective was 53.3%. CONCLUSIONS When the WTP threshold is 3 times China’s GDP per capita in 2023， tislelizumab plus chemotherapy is cost-effective for first-line treatment of locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma， compared with placebo plus chemotherapy.