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 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 analyze the effects of fluorine exposure on calcium ion metabolism and the expression of related calcium-regulating proteins in the kidneys of rats.Methods:Forty-five 5-week-old specific pathogen-free male Wistar rats (weighed 90 - 120 g) were selected and divided into three groups according to the randomized numeric table: 0 (control), 50, and 100 mg/L fluorine exposure groups, with 15 rats in each group. The control group was given deionized water, while the 50 and 100 mg/L fluorine exposure groups were given sodium fluoride solutions containing 50 and 100 mg/L fluorine ions, respectively. After 12 weeks, urine samples were collected, and kidneys and blood were harvested. Urinary fluorine levels were measured using a fluoride ion-selective electrode method. Calcium ion levels in the urine, kidneys, and serum were determinated using the methylthymol blue microplate method. The protein expression levels of transient receptor potential vanilloid receptor 5 (TRPV5), calbindin-D28K (CB-D28K), sodium-calcium exchanger-1 (NCX1), Klotho and plasma membrane calcium ATPase 1b (PMCA1b) in the kidneys were detected by Western blotting and immunohistochemistry.Results:The urinary fluorine levels in the control group and the 50 and 100 mg/L fluorine exposure groups were (0.48 ± 0.09), (20.01 ± 1.68), (37.45 ± 2.45) mg/L, respectively, with statistically significant differences between the groups ( F = 929.58, P < 0.001). Significant differences in calcium ion levels in urine, kidneys, and serum were observed among the three groups ( F = 14.66, 11.09, 10.31, P < 0.05). Compared with the control group, the 100 mg/L fluorine exposure group exhibited higher levels of calcium ion in the urine and kidneys, and lower serum calcium ion levels ( P < 0.05). The results of Western blotting analysis revealed that the protein expression levels of TRPV5 and CB-D28K in the kidneys increased with the increase of fluorine exposure level ( Z = 2.11, 2.11, P = 0.035). The protein expression level of NCX1 in the kidneys showed a decreasing trend with increasing fluorine exposure level ( Z = - 2.11, P = 0.035). Significant differences were also observed in the protein expression levels of Klotho and PMCA1b among the three groups ( F = 8.93, 7.08, P < 0.05). Compared with the control group, the 100 mg/L fluorine exposure group showed higher level of Klotho protein expression and lower level of PMCA1b protein expression in the kidneys ( P < 0.05). Immunohistochemical results indicated significant differences in the protein expression levels of TRPV5, CB-D28K, NCX1, and Klotho in the kidneys of the three groups ( F = 27.56, 24.94, 16.05, 32.72, P < 0.05). Compared with the control group, the protein expression levels of TRPV5, CB-D28K, and Klotho in kidneys of 50 and 100 mg/L fluorine exposure groups were higher, while the protein expression levels of NCX1 were lower ( P < 0.05). Conclusion:Fluorine exposure may cause calcium ion metabolism disorders by regulating the expression levels of Klotho and other calcium-regulating proteins in the kidneys.

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 explore the latent categories and influencing factors of health activation among community-dwelling older adults with chronic diseases.Methods:Older patients with chronic diseases attending three community health centers in Hefei City from August to December 2023 were selected for the study using the convenience sampling method. The survey utilized the General Information Questionnaire, Consumer Health Activation Index, Chinese version of the Life-Space Assessment, Social Support Rating Scale, and Simplified Coping Style Questionnaire. Mplus 8.3 software was applied for latent profile analysis to examine patients' health activation, and unordered multicategory Logistic regression was used to explore the factors influencing different categories of health activation.Results:A total of 382 questionnaires were distributed, and 368 valid questionnaires were recovered, with a valid recovery rate of 96.34%. Three latent categories of health activation existed in community-dwelling older adults with chronic diseases, which were named as low health activation-high efficiency-coping inability group (16.85%, 62/368) , medium health activation group (27.99%, 103/368) , and high activation perception-action group (55.16%, 203/368) . Multicategory logistic regression analysis indicated that place of residence, age, self-rated health status, life space, social support, and active coping strategies were significant factors influencing the health activation of different latent categories of community-dwelling older adults with chronic diseases (all P<0.05) . Conclusions:The health activation of community-dwelling older adults with chronic diseases can be classified into three latent categories. Primary healthcare providers should identify the characteristics of patients in different categories and implement targeted nursing interventions to enhance their health activation levels.

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 stable phase.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 apply quality function deployment(QFD)method to formulate management strategy for usage quality of medical equipment,so as to provide a reference for ensuring the safety of using medical equipment.Methods:A questionnaire about the guarantee for the requirement of usage quality of medical equipment was designed,so as to obtain the information of the users of clinical department of The Affiliated Xinghua Hospital to Kangda College of Nanjing Medical University for the requirement of usage quality of medical equipment in using medical equipment from February to April 2024,and confirm the important degree of the requirement.Then,the QFD method was adopted to convert the requirements of users for medical equipment to the required technical indicators of guaranteeing usage quality of medical equipment,and the priority technical guarantee measures of the important degree were quantitatively obtained.Results:A total of 478 questionnaires were issued,and 442 valid questionnaires were retrieved,and the valid recovery rate of questionnaire was 92.47%.The questionnaire identified and analyzed 12 requirements of three dimensions of users in using medical equipment,and they were converted to the top six technical guarantee measures of the strategy of quality management of using medical equipment,which included equipment function,criticality of equipment mission,type of service provider,compliance of rules and regulations,requirements of maintenance,and service life.Conclusion:QFD method can help medical engineering department to establish a management system of usage quality with quantitative analysis for medical equipment,and enhance the management level for the quality of medical equipment in medical institutions,and realize maximize benefit of medical equipment.

Objective To investigate the expression changes and clinical significance of serum pepsinogen(PG)and triggering receptor expressed on myeloid cells-1(TREM-1)in patients with reflux esophagitis(RE).Methods A total of 140 patients with RE who were treated from October 2021 to October 2023 were selected as the observation group,and 140 healthy adults who underwent physical examination during the same period were selected as the control group.Serum PG(PGⅠ and PGⅡ)and TREM-1 were detected by ELISA.Multivariate logistic regression was used to analyze the influencing factors of RE.Receiver operating characteristic(ROC)was used to analyze the diagnostic efficacy of serum PGⅠ,PGⅡ and TREM-1 levels for RE.Results The levels of interleukin(IL)-2,IL-6,Il-1β,PGⅡ,TREM-1 and tumor necrosis factor-α(TNF-α)in the observation group were significantly higher than those in the control group,while the level of PGⅠ was significantly lower than that in the control group(P<0.01).Serum IL-2,IL-6,IL-1β,TNF-α,PGⅡ and TREM-1 were risk factors for RE,while serum PGⅠ was a protective factor for RE(P<0.01).ROC curve analysis showed that the area under the ROC curve(AUC)of combined detection of PGⅠ,PGⅡ and TREM-1 in the diagnosis of RE was significantly higher than that of PGⅠ alone(Z=5.940,P<0.001)and PGⅡ alone(Z=6.764,P<0.001)and TREM-1 alone(Z=6.791,P<0.001).Conclusion The expression levels of serum PGⅡ and TREM-1 in patients with RE are increased,while the expression level of PGⅠ is decreased.The combined detection of the three can improve the diagnostic efficacy of RE.

ObjectiveTo study the mechanism of compound Xishu granules （CXG） in inhibiting the proliferation of hepatocellular carcinoma cells by regulating ferroptosis. MethodsThe transplanted tumor model of human Huh7 was established with nude mice and the successfully modeled mice were randomized into model， Fufang Banmao （0.21 g·kg^-1）， low-dose （1.87 g·kg^-1） CXG， medium-dose （3.74 g·kg^-1） CXG， and high-dose （7.49 g·kg^-1） CXG groups. Mice were administrated with drinking water or CXG for 28 days， and the body weight and tumor volume were measured every 4 days. Hematoxylin-eosin staining was employed to observe the histopathological changes of tumors. The cell-counting kit-8 （CCK-8） was used to examine the survival rate of Huh7 cells treated with different concentrations （0， 31.25， 62.5， 125， 250， 500， 1 000 mg·L^-1） of CXG for 24 h and 48 h. CA-AM， DCFH-DA， and C11-BODIPY^581/591 fluorescent probes were used to determine the intracellular levels of ferrous ion （Fe²⁺）， reactive oxygen species （ROS）， and lipid peroxide （LPO）， respectively. The colorimetric method was employed to measure the levels of glutathione （GSH） and superoxide dismutase （SOD）. Western blot was employed to determine the protein levels of glutathione peroxidase 4 （GPX4）， transferrin receptor 1 （TFR1）， and ferritin heavy chain 1 （FTH1）， respectively. ResultsIn the animal experiment， compared with the model group， the drug treatment groups showed reductions in the tumor volume from day 12 （P<0.01）. After treatment， the Fufang Banmao and low-， medium-， and high-dose CXG groups had lower tumor volume， relative tumor volume， and tumor weight than the model group （P<0.05）， with tumor inhibition rates of 48.99%， 79.93%， 91.38%， and 97.36%， respectively. Moreover， the CXG groups had lower tumor volume and relative tumor volume （P<0.05 in all the three dose groups） and lower tumor weight （P<0.05 in medium-dose and high-dose groups） than the Fufang Banmao group. Compared with the model group， the drug treatment groups showed reduced number of tumor cells， necrotic foci with karyopyknosis， nuclear fragmentation， and nucleolysis， and the high-dose CXG group showed an increase in the proportion of interstitial fibroblasts. In the cell experiment， compared with the blank group， CXG reduced the survival rate of Huh7 cells in a dose-dependent manner after incubation for 24 h and 48 h （P<0.05）. Compared with the blank group， the RSL3 group and the low-， medium-， and high-dose CXG groups showed a decrease in the relative fluorescence intensity of CA-AM and increases in the fluorescence intensity of DCFH-DA and fluorescence ratio of C11-BODIPY^581/591， which indicated elevations in the levels of Fe²⁺ （P<0.01）， ROS （P<0.05）， and LPO （P<0.01）， respectively. Compared with the blank group， the RSL3 and low-， medium-， and high-dose CXG groups showed lowered levels of GSH and SOD （P<0.05）. In addition， the RSL3 group and the medium- and high-dose CXG groups showed down-regulated expression of GPX4 and FTH1 （P<0.05）， and the low- and high-dose CXG groups presented up-regulated expression of TFR1 （P<0.05）. ConclusionCXG suppresses the proliferation of hepatocellular carcinoma cells by inducing ferroptosis via downregulating the GSH-GPX4 signaling axis and increasing intracellular Fe²⁺and LPO levels.

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.