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 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 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.

BACKGROUND:The formation of postoperative abdominal adhesions is a complicated process,and the prevention of postoperative adhesions is an urgent problem in clinic. OBJECTIVE:To analyze the mechanism of adhesion at cellular and molecular levels,and to provide theoretical basis for the prevention and treatment of adhesion by mesenchymal stem cell exosomes. METHODS:"Abdominal adhesion,pelvic adhesion,postoperative adhesion,epithelial mesenchymal transformation,mesenchymal stem cells,stem cell exosomes,mesenchymal stem cell exosomes"were selected as Chinese and English search terms.We searched PubMed,CNKI,and Chinese biomedical literature and screened relevant articles on postoperative abdominal adhesion and mesenchymal stem cell exosomal intervention published from inception to August 2023.After systematic analysis,54 articles were finally included for the review. RESULTS AND CONCLUSION:(1)Any pathological factors such as peritoneal inflammation,mechanical injury,tissue ischemia,and foreign body implantation cause peritoneal surface injury,resulting in postoperative abdominal adhesion.The formation process of adhesion includes the interaction of peritoneal mesothelial cell repair,inflammatory response,fibrinolytic system,coagulation pathway and other processes,involving a variety of cytokines and signaling pathways.Wnt/β-catenin pathway can induce fibrosis and angiogenesis,and cooperate with transforming growth factor-β/Smads signaling pathway to stimulate fibroblast proliferation and cause peritoneal fibrosis.Meanwhile,nuclear factor-κB signaling pathway up-regulates the expression of cellular inflammatory factors,promotes fibroblast proliferation,and plays a key role in the process of tissue fibrosis.(2)The paracrine function of stem cells is an important direction of molecular intervention in abdominal adhesions based on regenerative medicine.It can participate in a variety of complex cytokines and signaling pathways involved in abdominal adhesions.(3)Compared with traditional methods for treating abdominal adhesions,mesenchymal stem cell exosome has biological activity and is safe to use.Mesenchymal stem cell exosomes without special culture and expansion have lower immunogenicity,longer stability and other advantages,can guide a normal repair and healing through a variety of ways.(4)Mesenchymal stem cell exosome has been proven to be involved in regulating the above processes of adhesion formation in previous studies,showing potential application prospects in clinical studies.However,further clinical studies are needed to explore appropriate treatment options for mesenchymal stem cell exosomes to address the problem of clinical translation.

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.

Sucrose non-fermenting 1-related protein kinase 1 (SnRK1) is one of the highly conserved Ca²⁺ non-dependent serine/threonine protein kinases, playing a crucial role in regulating the stress responses, growth, and development of plants. SnRK1 is a three-subunit complex, and it is involved in responding to the signaling transduction induced by low-energy/low-sugar conditions. SnRK1 responds biotic and abiotic stress conditions (such as salt, drought, low/high temperatures, and diseases) through phosphorylation of key metabolic enzymes and regulatory proteins, regulation of transcription, and interactions with other proteins. Furthermore, SnRK1 is not only involved in hormone signaling pathways mediated by abscisic acid (ABA), jasmonic acid (JA) and salicylic acid (SA), but also regulates plant autophagy by inhibiting the activity of target of rapamycin (TOR). In this review, we summarized the current results of research on the discovery, structure, and classification of plant SnRK1 and its roles in the stress responses, growth, and development of plants. Furthermore, this article proposes the directions of future research. This review provides good genetic resources and a theoretical basis for the genetic improvement and biological breeding for enhancing the stress tolerance of crops.
Stress, Physiological/physiology* ; Protein Serine-Threonine Kinases/metabolism* ; Plant Development/genetics* ; Signal Transduction ; Gene Expression Regulation, Plant ; Plant Proteins/physiology* ; Plants/metabolism* ; Arabidopsis Proteins/physiology* ; Plant Growth Regulators/metabolism*

Objective To construct the animal model,and to study the expression and clinical signifi-cance of YKL-40 in the progress of chronic renal failure complicating cardiac dysfunction.Methods C57BL/6N mice were chosen as the experimental subjects and divided into the blank control(BC)group,renal failure(RF)group,heart failure(HF)group and renal combined heart failure group.The renal failure model was constructed by adenine perfusion.The heart failure model was constructed by subcutaneous injection of isopro-terenol.The renal failure and heart failure group model was established by adenine perfusion combined with subcutaneous injection of isoproterenol.The validity of constructed models was evaluated by creatinine(SCr),urea nitrogen(BUN)and BNP levels,renal ultrasound and ultrasonic cardiogram examination results.The levels of C-reactive protein(CRP)and YKL-40 were detected by ELISA,and the YKL-40 mRNA expression level in kidney and heart tissues was measure by RT-qPCR.The Image J software was used to calculate the collagen fiber area of the Masson staining results.Results Except the blank control group,the mice weights in the other 3 groups were decreased,and the differences were statistically significant(P＜0.05).SCr,BUN,average renal cross sectional area,average renal volume and renal CVF in the renal failure group and renal combined heart failure group were higher than those in the blank control group and heart failure group(P＜0.05).The levels of LVEF,LVCO,LVSV,LVFS,LVPWd and LVPWs in the heart failure group and renal combined heart failure group were lower than those in the blank control group and renal failure group(P＜0.05).LVEF and LVFS in the renal combined heart failure group were higher than those in the heart failure group(P＜0.05).Compared with the blank control group,the serum CRP and YKL-40 levels in the other three groups were higher(P＜0.05);the CRP and YKL-40 levels in the renal combined heart failure group were higher than those in the renal failure group and heart failure group(P＜0.05).In the myocardial tis-sues,the YKL-40 mRNA expression level in the heart failure group and renal combined heart failure group was higher than those in the blank control group and renal failure group(P＜0.05).YKL-40 had the correla-tion with CRP(r=0.88,P＜0.05).Serum YKL-40 had the correlation with renal tissue YKL-40 gene expres-sion(r=0.77,P＜0.05),and had the correlation with the renal tissue CVF(r=0.89,P＜0.05).Conclusion YKL-40 has the influencing effect on renal failure complicating heart dysfunction,and could serve as the biomarker to mo-nitor the renal insufficiency complicating heart function abnormality.

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.