Table1_Cost-effectiveness analysis of zolbetuximab plus mFOLFOX6 as the first-line treatment for CLDN18.2-positive, HER2-negative advanced gastric or Gastroesophageal Adenocarcinoma.docx

Background: The SPOTLIGHT trial demonstrated that zolbetuximab plus mFOLFOX6 (ZOL-FO) as a first-line regimen compared with placebo plus mFOLFOX6 (PLB-FO) conferred clinical benefits to patients with CLDN18.2-positive, HER2-negative advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. However, due to the high cost of zolbetuximab, whether ZOL-FO is cost-effective compared with PLB-FO is unclear. This study aimed to evaluate the cost-effectiveness of ZOL-FO as a first-line treatment option for CLDN18.2-positive, HER2-negative advanced G/GEJ adenocarcinoma from the perspective of the Chinese healthcare system.Methods: Markov models with three different health states were developed to assess the cost-effectiveness of ZOL-FO as a first-line treatment option for CLDN18.2-positive, HER2-negative advanced G/GEJ adenocarcinoma. Clinical efficacy data were obtained from the SPOTLIGHT trial; the drug’s cost was calculated at national bid prices, and other costs and utility values were obtained from the published literature. Outcomes included total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). The model’s robustness was verified using one-way sensitivity and probabilistic sensitivity analyses.Results: The ZOL-FO group gained 1.64 QALYs at $87,746.35, while the PLB-FO group gained 1.23 QALYs at$11,947.81. The ICER for ZOL-FO versus PLB-FO was $185,353.28 per QALY gained. The parameters exerting an important impact on the model results were the price of zolbetuximab, body surface area, and progression-free survival utility. At a willingness-to-pay threshold of$38,201/QALY, ZOL-FO had a 0% probability of cost-effectiveness compared with PLB-FO.Conclusion: From the perspective of the Chinese healthcare system, ZOL-FO is unlikely to be cost-effective as the first-line treatment option for CLDN18.2-positive, HER2-negative advanced G/GEJ adenocarcinoma.</p

Table1_Cost-effectiveness analysis of adebrelimab combined with chemotherapy for extensive-stage small cell lung cancer.pdf

Background: The findings of the CAPSTONE-1 trial showed that adebrelimab in combination with chemotherapy (etoposide-carboplatin) (ADCHM) is clinically beneficial as a first-line treatment for patients with extensive-stage small cell lung cancer (ES-SCLC), compared with placebo plus chemotherapy (PLCHM, etoposide-carboplatin). However, owing to the higher cost of adebrelimab, it is unclear whether ADCHM is cost-effective compared with PLCHM. This study aimed to evaluate the cost-effectiveness of ADCHM as a first-line treatment for patients with ES-SCLC from the perspective of the Chinese healthcare system.Methods: A Markov model with three health states was developed to assess the cost-effectiveness of ADCHM as a first-line treatment option with ES-SCLC. Clinical data were obtained from the CAPSTONE-1 trial. Costs of the drug were calculated at national tender prices, and other costs and utility values were obtained from published literature. The outcomes included life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). One-way sensitivity analysis and probabilistic sensitivity analysis were used to validate the robustness of the model.Results: The ADCHM group achieved 1.21 QALYs (2.47 LYs) for $25,312, whereas the PLCHM group achieved 0.81 QALYs (1.59 LYs) for$14,846. The ICER for ADCHM versus PLCHM was $25914 per QALY gained. The variables with the greatest impact on the model results were the utility value of progressive disease, the utility value of progression-free survival, and the price of adebrelimab (100 mg). At a willingness-to-pay threshold of$37,653/QALY, ADCHM had an 89.1% probability of being cost-effective compared with PLCHM.Conclusion: ADCHM may be a cost-effective first-line treatment strategy for ES-SCLC from the perspective of the Chinese healthcare system.</p

Table1_Cost-effectiveness analysis of transarterial chemoembolization combined with lenvatinib as the first-line treatment for advanced hepatocellular carcinoma.docx

Purpose: Results from the LAUNCH trial suggest transarterial chemoembolization (TACE) in combination with lenvatinib is significantly more effective than lenvatinib as a first-line treatment option for advanced hepatocellular carcinoma (HCC). However, the cost of TACE is substantial. This study compares the cost-effectiveness of TACE in combination with lenvatinib (TACE-LEN) with that of lenvatinib alone as the first-line treatment for advanced HCC from the perspective of the Chinese healthcare system.Methods: Markov models of different health states were constructed to simulate first-line treatment, disease progression, and survival in patients with advanced HCC. Clinical efficacy was obtained from the LAUNCH trial. The cost of drugs was sourced from national tender prices, and the treatment cost of weight-decreased was obtained from the Fujian Provincial Bureau of Prices. Other costs and utility values were based on the published literature. Total costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) comprised the model output. One-way and probabilistic sensitivity analyses were performed to validate model robustness and subgroup analyses were also conducted.Results: Analysis of the model showed that compared to lenvatinib, TACE-LEN improved effectiveness by 1.60 QALYs at a total cost increase of $48,874.69, with an ICER value of$30,482.13/QALY. A one-way sensitivity analysis found that the progression-free survival utility value per year had the greatest impact on the model. A probabilistic sensitivity analysis showed that TACE-LEN had a 97.9% probability of being cost-effective as the first-line treatment option for advanced HCC compared to lenvatinib when the willingness-to-pay (WTP) value was $38,201/QALY (three times the Chinese GDP per capita in 2022). Subgroup analysis showed that all subgroups of patients preferred TACE-LEN. However, when the WTP threshold was below$30,300/QALY, TACE-LEN is no longer cost-effective.Conclusion: Our study found TACE-LEN to be a cost-effective treatment option for patients with advanced HCC compared to lenvatinib from a Chinese healthcare system perspective, but not so in low-income provinces in China.</p

Image_1_Cost-effectiveness analysis of sintilimab plus chemotherapy for advanced or metastatic esophageal squamous cell carcinoma.tif

BackgroundSintilimab plus chemotherapy (SIDCHM) is more effective than placebo plus chemotherapy (PLCHM) for advanced or metastatic esophageal squamous cell carcinoma (ESCC). However, considering the high cost of sintilimab, this study evaluated the cost-effectiveness of SIDCHM in comparison with PLCHM for advanced or metastatic ESCC from the Chinese healthcare system perspective.MethodsPolymorphic Markov models were constructed to simulate the course and cost of SIDCHM. Treatment drug costs were calculated at national list prices and clinical data, other costs, and utility values were extracted from the reference literature. Primary outcomes included quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). The robustness of the model was verified by one-way sensitivity analysis and probabilistic sensitivity analysis (PSA).ResultsSIDCHM obtained 1.03 QALYs at $24,044.49, whereas the effectiveness and cost of PLCHM were 0.67 QALYs and$14,166.24, respectively. The ICER for SIDCHM versus PLCHM was $23,458.08/QALY. The utility of the PFS state was the parameter that had the greatest effect on the ICER. The PSA showed that SIDCHM had an 86$37,653/QALY).ConclusionFrom the Chinese healthcare system perspective, SIDCHM is considered a cost-effective treatment option compared with PLCHM as first-line therapy for advanced or metastatic ESCC.</p

Azobenzene-Semicarbazone Enables Optical Control of Insect Sodium Channels and Behavior

Photopharmacology uses molecular photoswitches to establish control over the action of bioactive molecules. The application of photopharmacology in the research of invertebrate sodium channels has not been investigated. Here we report several photochromic ligands of metaflumizone. One ligand, termed ABM04, underwent reversible trans–cis isomerization under ultraviolet or blue light irradiation. cis-ABM04 had excellent larvicidal activity against mosquito larvae with an LC50 value of 4.39 μM and showed insecticidal activity against Mythimna separata with an LC50 value of 7.19 μM. However, trans-ABM04 was not found to have biological activity. ABM04 (10 μM) can induce depolarization of dorsal unpaired median neurons and enable the real-time photoregulation of mosquito larval behavior. The precise regulation of invertebrate sodium channels is realized for the first time, which provides a new strategy for the basic and accurate research of invertebrate sodium channels

Synthesis, Insecticidal Activities, and 3D-QASR of <i>N</i>‑Pyridylpyrazole Amide Derivatives Containing a Phthalimide as Potential Ryanodine Receptor Activators

To develop potent and environment-friendly insecticides, novel N-pyridylpyrazole amide derivatives containing a phthalimide were designed and synthesized. The preliminary bioassay results showed that most of the target compounds exhibited good insecticidal activities. For oriental armyworm (Mythimna separata), compounds E5, E29, E30, and E33 displayed higher than 90% lethal rates at 25 mg L–1. In particular, compound E33 displayed 60% mortality at a lower concentration of 6.25 mg L–1. Besides, compound E33 also showed a 30% lethal rate at 5 mg L–1 against diamondback moth (DBM) (Plutella xylostella). Molecular docking between the most active compound E33 and DBM ryanodine receptor (RyR), comparative molecular field analysis (CoMFA), and density functional theory (DFT) calculations were conducted and discussed. Furthermore, according to vitro studies using a calcium imaging technique, compound E33 was a potent novel lead targeting insect RyR

Supplementary Figure S4 from Dual Inhibition of Bcr-Abl and Hsp90 by C086 Potently Inhibits the Proliferation of Imatinib-Resistant CML Cells

Supplementary Figure S4. C086 potently inhibits the growth of human leukemia progenitor/stem cells.</p

Supplementary Figure S1 from Dual Inhibition of Bcr-Abl and Hsp90 by C086 Potently Inhibits the Proliferation of Imatinib-Resistant CML Cells

Supplementary Figure S1. C086 induces apoptosis in imatinib-sensitive and -resistant CML cells.</p

Supplementary Figure S5 from Dual Inhibition of Bcr-Abl and Hsp90 by C086 Potently Inhibits the Proliferation of Imatinib-Resistant CML Cells

Supplementary Figure S5. C086 treatment does not affect the engraftment of normal bone marrow cells in NOD-SCID mice.</p

Supplementary Figure S3 from Dual Inhibition of Bcr-Abl and Hsp90 by C086 Potently Inhibits the Proliferation of Imatinib-Resistant CML Cells

Supplementary Figure S3. Effects of C086 on cell cycle progression.</p