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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.
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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.
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OBJECTIVE To evaluate the cost-effectiveness of denosumab and teriparatide in the treatment of postmenopausal osteoporosis in Chinese women， and provide reference for relevant decision-making. METHODS From the perspective of health system in China， Excel 2003 was used to establish Markov model， and cost-utility analysis was used to evaluate the cost- effectiveness of denosumab or teriparatide combined with Calcium carbonate D3 tablets in the treatment of postmenopausal osteoporosis in Chinese women. Pharmacotherapy effects were obtained with network meta-analysis， and cost and health utility value data were obtained from published literature. The model cycle was 1 year， and the simulation time limit was the patient’s lifetime. Univariate sensitivity analysis and probabilistic sensitivity analysis were used to evaluate the effects of model parameter changes on the robustness of the results. Through scenario analysis， the cost-effectiveness of domestic drug cost used as drug cost of terlipatide group was discussed； the influence of residual effects of teriparatide on the results and the cost-effectiveness of sequential use of desumamab after terlipatide withdrawal were also discussed. RESULTS The effect of denosumab regimen was better than that of terlipatide regimen [13.24 quality-adjusted life years （QALYs） vs. 12.96 QALYs]， with lower cost （51 224.64 yuan vs. 167 102.67 yuan）， denosumab regimen was the absolutely superior regimen. The results of single factor sensitivity analysis showed that the cost and discount rate of Terlipatide injection had greater impact on the results. The results of probability sensitivity analysis showed that when three times of China’s per capita gross domestic product （GDP） in 2021 was used as the threshold of willingness to pay， the probability of cost-effectiveness of denosumab regimen was 93.5%. The results of scenario analysis showed that， whether the drug cost of terlipatide regimen which was replaced by domestic drugs， or the residual effect of terlipatide was considered， or desulmonab was used sequentially after two years of terlipide treatment， denosumab regimen was always the absolute advantage regimen. CONCLUSIONS Denosumab combined with Calcium carbonate D3 tablets is more cost-effective than teriparatide combined with Calcium carbonate D3 tablets in the treatment of postmenopausal osteoporosis in Chinese women.
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OBJECTIVE To study the role of phosphatidylinositol-3-kinase （PI3K） on sunitinib-induced myocardial systolic dysfunction. METHODS Using human-induced pluripotent stem cell-derived cardiomyocytes （hiPSC-CMS） as objects， the contractile force of cardiomyocytes was measured by CardioExcyte 96 system， and IC50 of sunitinib was calculated after hiPSC- CMS were treated with sunitinib at different concentrations [0 （control）， 0.5， 1， 3， 5， 10 μmol/L] for 24 hours. The effects of sunitinib （3.14 μmol/L） on the contractile frequency of cardiomyocytes， calcium transient amplitude and calcium transient recovery time course， mRNA expression of myocardial injury markers atrial natriuretic peptide （ANP）， brain natriuretic peptide （BNP） and β-myosin heavy chain （β-MHC） were detected. PI3K activator 3，4，5-triphosphate phos-phatidylinositol （PIP3， 1 μmol/L） and sunitinib were used to intervene in hiPSC-CMs jointly， so as to investigate the role of PI3K in the myocardial systolic dysfunction induced by sunitinib. RESULTS Sunitinib inhibited the contractile force of hiPSC-CMs in a concentration-dependent manner. IC50 of sunitinib was 3.14 μmol/L. After intervention with 3.14 μmol/L sunitinib， the contractile frequency of hiPSC-CMs and calcium transient amplitude were decreased significantly （P＜0.05 or P＜0.01）； the duration of calcium transient recovery was prolonged significantly （P＜0.05）， and mRNA expressions of ANP， BNP and β-MHC were significantly increased （P＜0.01）. After PI3K was activated with PIP3， the contractile force of hiPSC-CMs was increased significantly （P＜0.01）. CONCLUSIONS Activating PI3K activity is a potential molecular mechanism to improve myocardial toxicity induced by sunitinib.
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OBJECTIVE To evaluate the economics of serplulimab combined with chemotherapy regimens for the first-line treatment of extensive-stage small cell lung cancer （ES-SCLC） from the perspective of health system in China. METHODS A partitioned survival model was constructed based on the ASTRUM-005 clinical trial and related literature data， with a model simulation time frame of 10 years and a 3-week cycle， and both cost and utility values were discounted using a 5% discount rate. The quality-adjusted life year （QALY） was used as a model output indicator and the incremental cost-effectiveness ratio （ICER） was calculated to evaluate the economics of serplulimab combined with chemotherapy regimens （serplulimab group） versus chemotherapy alone regimens （chemotherapy alone group） for the first-line treatment of ES-SCLC. One-way sensitivity analysis and probabilistic sensitivity analysis were used to verify the robustness of the results of the base-case analysis and to conduct a scenario analysis for the serplulimab patient assistance program. RESULTS The results of the base-case analysis showed that compared with chemotherapy alone group， ICER of serplulimab group was 758 690.27 yuan/QALY， which was higher than 3 times China’s per capita gross domestic product （GDP） in 2022 as the willingness-to-pay （WTP） threshold. The results of the scenario analysis showed that compared with chemotherapy alone group， the ICER of serplulimab group was 172 275.74 yuan/QALY， which was below above WTP threshold. The one-way sensitivity analysis showed that the progress-free survival utility value， serplulimab price and so on had a significant impact on the model results. The results of the probabilistic sensitivity analysis showed that the probability of the serplulimab group being economic was 0 when the serplulimab patient assistance program was not considered， but 100% when the patient assistance program was considered. CONCLUSIONS At a WTP threshold of 3 times China’s per capita GDP in 2022， the serplulimab group is no cost-effectiveness compared to the chemotherapy alone group； however， this result is reversed when the patient assistance program is taken into account.
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OBJECTIVE To evaluate the cost-effectiveness of denosumab and zoledronic acid in the treatment of postmenopausal osteoporosis ，and to provide reference for relevant decision-making. METHODS From the perspective of Chinese health system ，Excel 2003 software was used to establish Markov model ，and cost-utility analysis was used to evaluate the cost-effectiveness of denosumab or zoledronic acid combined with calcium carbonate D 3 in the treatment of postmenopausal osteoporosis. Pharmacotherapy effects were obtained from the network Meta-analysis ，and cost and health-utility value data were obtained from the published literature or network ，etc. The model cycle was 1 year，and the simulation time limit was the patient ’s lifetime. One-way sensitivity analysis and probabilistic sensitivity analysis were used to evaluate the impact of model parameter changes on the robustness of the results ；and the cost-effectiveness of changing the medication cycle of zoledronic acid were explored through scenario analysis. RESULTS Denosumab regimen was more effective than zoledronic acid regimen （12.77 QALYs vs. 11.98 QALYs），and its cost was also higher than zoledronic acid regimen （51 224.56 yuan vs. 49 221.67 yuan）， and the incremental cost-effectiveness ratio was 2 544.14 yuan/QALY. One-way sensitivity analysis showed that the cost of Zoledronic acid injection and that of Denosumab injection had great impact on the results. The results of probabilistic sensitivity analysis showed that when using 3 times of per capita gross domestic product （GDP）in China in 2021 as the threshold of willingness to pay ，the probability of Denosumab regimen being cost-effective was 85.4％. The results of the scenario analysis showed that the Denosumab regimen was still more cost-effective when the dosing cycle of zoledronic acid was changed. CONCLUSIONS Under the threshold of 1-3 times of Chinese per capita GDP in 2021，denosumab combined with calcium carbonate D 3 is more cost-effective than zoledronic acid combined with calcium carbonate D 3 in the treatment of postmenopausal osteoporosis.
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OBJECTIVE To systematically evaluate the economical efficiency of marketed a naplastic lymphoma kinase （ALK）-tyrosine kinase inhibitors （TKI）for the treatment of ALK-positive non-small cell lung cancer （NSCLC）in China ，and to provide a reference for the selection of China ’s medical insurance list and drug pricing. METHODS Computer searches of databases such as CNKI ，Wanfang database ，VIP，PubMed，Embase and the Cochrane Library were conducted to collect pharmacoeconomic evaluation studies of four marketed ALK-TKI （crizotinib，seretinib，aletinib and ensatinib ）in the treatment of ALK-positive NSCLC in China during the inception to July 2021. The qualities of the included literature were evaluated using CHEERS checklist ，and analyzed systematically in terms of both methodological and economic outcomes. RESULTS A total of 6 literatures were included ，with a compliance rate of 71％ to 83％ for the CHEERS list criteria ，and the overall quality of the literature was high. In terms of methodological analysis ，the pharmacoeconomic evaluation methods included in the study were mainly model-based （Markov or partitioned survival models ） and real-world data-based cost-utility analysis. Most research perspectives were health insurance payer and health system perspectives ；all cost types were direct medical costs. In terms of economical efficiency analysis ，compared with chemotherapy plan ，2 studies confirmed that ALK-TKI （crizotinib，seretinib）were not economic ，1 study confirmed ALK-TKI （crizotinib） showed economical efficiency. Seretinib showed relatively higher economical efficiency when compared to other ALK-TKIs. High drug prices were the main factor why ALK-TKI was not economically viable for treating ALK-positive NSCLC. CONCLUSIONS The second-generation ALK-TKI （seretinib， 163.com alectinib） have better economical efficiency than the first-generation ALK-TKI （crizotinib）. The economical efficiency of seretinib is the best among the second-generation · ALK-TKI. The economical efficiency of chemotherapy regimen is better than that of the second-generation ALK-TKI （seretinib）. Economic comparison between chemotherapy and first-generation ALK-TKI （crizotinib）remains controversial.
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OBJECTIVE To evaluate the cost-utility of pembrolizumab combined with chemotherapy versus chemotherapy alone in the first-line treatment of advanced or metastatic esophageal carcinoma. METHODS Cost-utility analysis of pembrolizumab combined with chemotherapy versus chemotherapy alone for advanced or metastatic esophageal carcinoma was conducted by using a three-state partitioned survival model from the perspective of health system in China. The model use d a lifetime simulation time frame with 3 weeks as a cycle. The survival data were extrapolated using KEYNOTE- 590 data；cost data were obtained from the median of 2022 public winning bid on Yaozhi network ，among which the price of pembrolizumab was obtained after discounting by a patient assistance program ；utility data were obtained from the literatures ，and a 5％ discount rate was used for both cost and utility. One-way sensitivity analysis and probabilistic sensitivity analysis were also conducted to examine model robustness. RESULTS Analysis of the base case results showed that compared to chemotherapy alone ，the incremental cost-effectiveness ratio （ICER）of pembrolizumab combined with chemotherapy regimens were 950 528.42 yuan/QALY，107 845.39 yuan/QALY and 315 754.56 yuan/QALY for esophageal squamous cell carcinoma （ESCC），programmed deathligand- 1 combined positive score （PD-L1 CPS）≥10 and intention-to-treat population （ITT），respectively. The results of sensitivity analysis verified the robustness of the basic analysis results. CONCLUSIONS Under our healthcare system ，using a threshold of willingness-to-pay of 1-3 times our GDP per capita in 2021，pembrolizumab combined with chemotherapy regimen isn ’t cost-utility compared with chemotherapy alone in the ESCC and ITT subgroups of patients ，while it is cost-utility in the PD-L 1 CPS≥10 subgroup of patients.
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OBJECTIVE To evaluate the cost-effectiveness of durvalumab for consolidation therapy after chemoradiotherapy for unresectable stage Ⅲ non-small cell lung cancer from the perspective of the Chinese health care system. METHODS A Markov model was developed by using updated four-year survival data from the PACIFIC trial in May 2021 and relevant literature. The cost-effectiveness of durvalumab for consolidation therapy after chemoradiotherapy for unresectable stage Ⅲ non-small cell lung cancer was evaluated by using quality-adjusted life years （QALYs）as health output index with 20-year simulation time frame and a 2-week cycling period. The costs and health output were discounted using discount rate of 5％；one-way sensitivity analysis and probabilistic sensitivity analysis were used to examine the robustness of the model simulation results. RESULTS The results of the base analysis showed that compared with placebo group ，durvalumab resulted in 0.73 QALYs at an incremental cost of 1 076 062.86 yuan and an incremental cost-utility ratio （ICER）of 1 467 546.54 yuan/QALY，which was much higher than 3-fold per capita gross domestic products （GDP）in 2020（217 713 yuan）as willingness-to-pay （WTP）threshold. The results of one-way sensitivity analysis showed that the price of durvalumab and discount rate had a great impact on ICER. Probabilistic sensitivity analysis showed no cost-effective advantage for durvalumab when the WTP threshold was three times of GDP per capita in 2020 （217 713 yuan）. CONCLUSIONS From the perspective of Chinese health care system ，there is no cost-effective advantage to the use of durvalumab for consolidation therapy after chemoradiotherapy for unresectable stage Ⅲ non-small cell lung cancer when the WTP threshold was three times of GDP per capita in 2020.
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OBJECTIVE：To evaluate the economics of atezolizumab combined with stardard chemotherapy regimens versus chemotherapy regimens alone as first-line treatment for extensive-stage small-cell lung cancer （ES-SCLC）from the healthcare system perspective. METHODS ：A partitioned survival model was constructed using published phase Ⅲ clinical trial data （IMpower133）and literature data to evaluate the economics of atezolizumaba combined with standard chemotherapy regimens versus chemotherapy regimens alone as first-line treatment for ES-SCLC. One-way sensitivity analysis and probabilistic sensitivity analysis were used to evaluate the stability of the results. RESULTS ：The results of cost-utility analysis showed that the cost of atezolizumab combined with chemotherapy group was 489 598.52 yuan，with utility of 0.70 QALYs；the cost of chemotherapy alone group was 126 276.80 yuan，with utility of 0.55 QALYs；the incremental cost-utility ratio （ICUR）between the two groups was 2 361 709.05 yuan/QALY，far exceeding the willingness-to-pay （WTP）in China （3 times of GDP per capita in 2019，212 676 yuan）. One-way sensitivity analysis showed that progression-free utility value of atezolizumab combined with chemotherapy had the greatest impact on the results of cost-utility analysis ；probabilistic sensitivity analysis suggested that the atezolizumab combined with chemotherapy regimen was not economical within the WTP range of 0-500 000 yuan/QALY. CONCLUSIONS ：Atezolizumab combined with chemotherapy regimen has no cost-utility advantage versus chemotherapy alone in the first-line treatment of ES-CLC under the current economic level of China.
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Objective To further strengthen the management of radiological health technical service institutions, standardize their technical service behaviors, and explore the supervision countermeasures for radiological health and technical service institutions. Methods The radiological health technical service institutions status questionnaires s were designed to survey the basic situation, professionals and technical personnel, the equipment configuration, testing items and workload of service institutions. Results By the end of 2019, there were 23 radiological health technical service institutions in Hebei province, including 8 disease control and occupational prevention institutions (accounting for 34.8%) and 15 third-party institutions (accounting for 65.2%); The distribution of regional agencies were unbalanced; There were 223 professional and technical personnel, of which 29.6% were senior technical professionals, 29.6% were intermediate technical professionals and 40.8% were other professionals.58.8% had a bachelor's degree or above, and 41.2% had a college degree or below; The majors of professionals were relatively scattered, with only 6.44% of radiological health, 5.15% of physics-related majors, and 51.07% of medical-related majors. Other majors involve chemical pharmacy, environmental engineering, public relations planning, food, English, accounting and other majors.The professional technical responsible person had no part-time job;. The institution were totally equipped with 308 sets of radiation protection detectors and 172 sets of phantoms, basically in line with the configuration requirements; All quality control system documents such as quality management manuals, procedural documents, operating procedures, and work instructions have been established; All test items applied by laboratory measurement certification have passed;Conclusion The CDC institutions were gradually shrinking, the private institutions were gradually increasing and the nature of the institutions was gradually diversified.The allocation of regional resources was unbalanced.It is suggestedto strengthen the training on the theoretical basis and professional skills of professionals in testing and evaluation. Increasing on-site practical training is a more important and effective way.It is recommended to strengthen the training of basic-level health administrative departments and supervisory agencies and improvethe sense of responsibility of supervisors.
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OBJECTIVE：To evaluate the economic s of osimertinib versus first-generation EGFR-TKIs in the first-line treatment of EGFR mutation-positive locally advanced or metastatic non-small cell lung cancer （NSCLC），and to provide evidence-based reference for medical and healthy decision-making in China. METHODS ：From respective of health care system ，Markov model was developed by using patientsurvival data and published literature datato simulate 10 years of direct medical costs and quality-adjusted life years （QALY）for EGFR mutation-positive locally advanced or metastatic NSCLC patients ，with a model cycle length of 3 weeks，and the discount rate of 5％. One-way sensitivity analysis and probabilistic sensitivity analysis were used to evaluate the effects of parameter changes on the stability of the model results. RESULTS ：In the base-case analysis ，compared with the first-generation EGFR-TKIs ，osimertinib could obtain 0.40 QALYs more ，with an incremental cost of 163 531.55 yuan and an incremental cost-utility ratio （ICER）of 409 321.54 yuan/QALY，which was higher than the willingness-to-pay （WTP）threshold in China（3 times per capita GDP in China in 2019 of 212 676 yuan/QALY）. The results of one-way sensitivity analysis showed that the utility value of progression-free survival status and the price of osimertinib had the greatest impact on ICER. The results of probability sensitivity analysis showed that the probability of osimertinib to be cost-effective was 11.00％ at the WTP threshold in China. When the price of osimertinib decreased by 30％，50％ and 70％，the probability of osimertinib to be cost-effective was 26.20％，47.40％，and 74.30％ at the WTP threshold of 212 676 yuan/QALY，respectively. CONCLUSIONS ：When Chinese 3 times per capita GDP in 2019 is used as the criterion for judgment ，osimertinib is not economical compared with the first-generation EGFR-TKIs in first-line treatment of locally advanced or metastatic NSCLC with EGFR mutation-positive. Appropriate price reduction can improve its economy.
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OBJECTIVE：To ev aluate the economics of pembrolizumab versus first-line chemotherapy in the treatment of advanced non-small cell lung cancer with high programmed cell death protein ligand 1（PD-L1）expression from the perspective of Chinese healthcare system. METHODS ：Published KEYNOTE- 042 clinical trial data and relevant literature data were used to establish a Markov model to evaluate the economics of pembrolizumab versus first-line chemotherapy with a 20-years horizon and a 3-week cycle length ，discounting costs and utilities using a discount rate of 5％. One-way sensitivity analysis and probabilistic sensitivity analysis were used to evaluate the stability of the model results. RESULTS ：The base-case results showed that pembrolizumab yield additional 1.62 QALYs more than first-line chemotherapy ，with an incremental cost of 54 648 yuan；the incremental cost-utility ratio was 33 686 yuan/QALY，which was lower than the willingness-to-pay threshold （WTP）in China. The results of one-way sensitivity analysis showed that the price of nivolumab ，the price of pembrolizumab and the proportion of patients who received second-line immunotherapy in first-line chemotherapy group had the greatest impact on the results. The results of probabilistic sensitivity analysis showed that the probability of pembrolizumab to be cost-effective gradually increased within the WTP of 0-140 000/QALY. When WTP was 70 892 yuan/QALY（one time of the per capita GDP of China in 2019），the probability of pembrolizumab to be cost-effective was 95％. When WTP beyond 100 000 yuan/QALY，the probability of pembrolizumab to be cost-effective was 100％. CONCLUSIONS ：Pembrolizumab has economic advantages than first-line chemotherapy in the first-line treatment of non-small cell lung cancer with high PD-L 1 expression in China.
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Neutrophils, the most abundant leukocytes in human blood, are essential fighter immune cells against microbial infection. Based on the finding that neutrophils can either restrict or promote cancer progression, tumor-associated neutrophils (TAN) are classified into anti-tumor N1 and pro-tumor N2 subsets. One of the major mechanisms underlying the tumor-promoting function of N2-TANs is suppression of adaptive immune cells, in particular, cytotoxic T lymphocytes. Currently, no established methodologies are available that can unequivocally distinguish immunosuppressive TANs and granulocytic/polymorphonuclear myeloid-derived suppressor cells (G/PMN-MDSC). In view of the critical role of PMN-MDSCs in immune evasion and resistance to cancer immunotherapy, as established from data obtained with diverse cancer models, therapeutic strategies targeting these cells have been actively developed to enhance the efficacy of immunotherapy. Here, we have reviewed the available literature on strategies targeting PMN-MDSCs and summarized the findings into four categories: (1) depletion of existing PMN-MDSCs, (2) blockade of the development of PMN-MDSCs, (3) blockade of PMN-MDSC recruitment, (4) inhibition of immunosuppressive function. Owing to their high mobility to inflamed organs and ability to trespass the blood-brain barrier, neutrophils are outstanding candidate carriers in nanoparticle-based therapies. Another attractive application of neutrophils in cancer therapy is the use of neutrophil membrane-derived nanovesicles as a surrogate of extracellular vesicles for more efficient and scalable drug delivery. In the second part of the review, we have highlighted recent advances in the field of neutrophil-based cancer drug delivery. Overall, we believe that neutrophil-based therapeutics are a rapidly growing area of cancer therapy with significant potential benefits.
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Antineoplastic Agents/administration & dosage , Drug Carriers , Immunotherapy/methods , Neoplasms/therapy , Neutrophils/immunology , Cell Line, Tumor , Drug Resistance, Neoplasm/immunology , Humans , Immunotherapy/trends , Nanoparticles , Neoplasms/immunology , Neoplasms/pathology , Neutrophils/cytology , Tumor Escape/immunology , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunologyABSTRACT
Magnetic resonance based electrical properties tomography (MREPT) is a different method from proton density imaging, Bloch-Siegert shift (BSS) is used in this paper to reconstruct the radiofrequency (RF) field amplitude and calculate the distribution of the permittivity constant. The phase of the RF field is approximated by the phase component of the magnetization intensity, and the conductivity distribution is calculated. In the experiment, Bruker 7.0 T magnetic resonance device was used to image two water models and in vivo Balb/c mice to obtain the image of electrical characteristics. Experimental results show that the Bloch-siegert B1+ image is significantly more efficient than the double-angle B1+ image. The study can provide a reference for selecting appropriate B1 mapping technology for B1 field imaging of electrical characteristics organizations, and provide basic research support for promoting the practical application of magnetic resonance characteristics.
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Animals , Mice , Algorithms , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Phantoms, Imaging , TomographyABSTRACT
As drug carriers, magnetic nanoparticles can specifically bind to tumors and have the potential for targeted therapy. It is of great significance to explore non-invasive imaging methods that can detect the distribution of magnetic nanoparticles. Based on the mechanism that magnetic nanoparticles can generate ultrasonic waves through the pulsed magnetic field excitation, the sound pressure wave equation containing the concentration information of magnetic nanoparticles was derived. Using the finite element method and the analytical solution, the consistent transient pulsed magnetic field was obtained. A three-dimensional simulation model was constructed for the coupling calculation of electromagnetic field and sound field. The simulation results verified that the sound pressure waveform at the detection point reflected the position of magnetic nanoparticles in biological tissue. Using the sound pressure data detected by the ultrasonic transducer, the B-scan imaging of the magnetic nanoparticles was achieved. The maximum error of the target area position was 1.56%, and the magnetic nanoparticles regions with different concentrations were distinguished by comparing the amplitude of the boundary signals in the image. Studies in this paper indicate that B-scan imaging can quickly and accurately obtain the dimensional and positional information of the target region and is expected to be used for the detection of magnetic nanoparticles in targeted therapy.
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Acoustics , Computer Simulation , Magnetics , Magnetite Nanoparticles , TomographyABSTRACT
OBJECTIVE：To evaluate the drug economy of ixekizumab in the treatment of moderate-to-severe plaque psoriasis. METHODS： Literatures were retrieved from PubMed ， Embase， The Cochrane Library ， CNKI and Wanfang database ， supplemented by manual search ，search time from the database establishment to Oct. 31st，2019，using Chinese and English search terms included “Ixekizumab”“Taltz”“Psoriasis”“Pharmacoeconomics”“Cost-benifit analysis ”“Cost-effectiveness analysis ” “Cost-utility analysis ”，etc. The literatures were screened according to inclusion and exclusion criteria. Relevant pharmacoeconomic studies about ixekizumab in the treatment of moderate-to-severe plaque psoriasis were collected ，and the study methods and pharmacoeconomic evaluation results were summarized. RESULTS ：A total of 8 literatures were included ，involving 9 studies. The overall quality of the studies was high. All the studies were distributed in foreign countries such as Canada ，the United States and the United Kingdom. All the studies adopted Markov model. The health outcomes showed that ixekizumab could bring more quality-adjusted life years. Compared with methotrexate combined with phototherapy ，infliximab，ustekinumab and secukinumab ， the incremental cost-utility ratio （ICUR）of ixekizumab was different in different studies. CONCLUSIONS ：Ixekizumab has certain economic advantages for the treatment of moderate-to-severe plaque psoriasis ，but there is still a lack of relevant research in China and it is urgent to carry out relevant research suitable for Chinese.
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OBJECTIVE@#: To analyze experimental factors affecting recovery of puerarin in microdialysis.@*METHODS@#: Puerarin concentration in microdialysate samples was determined by high performance liquid chromatography. The methods of direct dialysis, retrodialysis and the zero-net flux were used to calculate recovery, respectively. The effects of perfusate composition, the analyte concentration, perfusate flow rate, medium temperature and stir rates of the dialysis medium on recovery were investigated.@*RESULTS@#: There were significant differences in the recovery values among direct dialysis, retrodialysis and zero-net flux methods. The recovery for 0.9% NaCl solution, Ringer's solution, PBS and anticoagulant dextrose solution as perfusate fluid were (71.25±2.36)%,(73.48±1.41)%,(68.50±2.43)% and (74.98±1.16)%, respectively. The composition of perfusate fluid had significant influence on the recovery(<0.01). At the same flow rate, recovery was independent of the analyte concentration. At the same concentration, the recovery was decrease with the increasing flow rate in an exponential relationship. The recovery increased with the raising temperature and stir rate of the dialysis medium, and the recovery remained stable when the stir rate reached above 200 rpm.@*CONCLUSIONS@#: A study method for recovery of puerarin in microdialysis has been established, and the recovery of puerarin is affected by calculating methods, perfusate fluids, flow rate, medium temperature and stir rate, but not affected by analyte concentrations.
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Chemistry Techniques, Analytical , Methods , Chromatography, High Pressure Liquid , Isoflavones , MicrodialysisABSTRACT
This study is aimed to make a comprehensive introduction to the anti-MRSA drugs,and also to compare the safety and efficacy among a variety of anti-MRSA drugs.Finally,it is pointed that we should select the anti-MRSA drugs precisely according to different situation of disease when treating the infection with MRSA.Then we can make the individualized treatment for patients and provide a basis for the disease when treatment of patients as well.
ABSTRACT
Objective To evaluate the effects of autologous blood withdrawal-reinfusion on inflam-matory responses of patients undergoing cardiac surgery with different time courses of cardiopulmonary by-pass(CPB). Methods A total of 120 patients, aged 18-70 yr, of American Society of Anesthesiologists physical status Ⅱ-Ⅳ, were divided into 2 groups(n=60 each)using a random number table: autologous blood withdrawal-reinfusion group(ABWR group)and non-autologous blood withdrawal-reinfusion group (NABWR group). Each group was further divided into 3 subgroups(n=20 each)according to the expected time of CPB: long time course(>120 min)subgroup(L subgroup), medium time course(>60 min-≤120 min)subgroup(M subgroup)and short time course(≤60 min)subgroup(S subgroup). In group ABWR, after the end of CPB and after heparin was reversed with protamine, blood shed from the surgical field and left in the autologous blood recycling machine pipeline after the end of CPB was collected, filtra-ted, washed, concentrated and reinfused. After the end of CPB, blood left in the autologous blood recy-cling machine pipeline was directly kept in the storage bag and partially or totally reinfused in group NAB-WR. Before operation and at 1, 6, 24 and 48 h after the end of CPB, blood samples were collected for de-termination of serum tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6)and IL-10 concentrations by enzyme-linked immunosorbent assay. Results Compared with ABWR-S subgroup, the serum TNF-α and IL-6 concentrations were significantly increased at each time point after the end of CPB(P<005), and no significant change was found in serum IL-10 concentrations in ABWR-L and ABWR-M subgroups (P>005). There were no significant differences in serum TNF-α, IL-6 and IL-10 concentrations between ABWR-L subgroup and ABWR-M subgroup(P>005). Compared with NABWR subgroup of the same time course, the serum TNF-α concentration was significantly decreased at each time point after the end of CPB, the serum IL-6 concentration was decreased at 6-48 h after the end of CPB(P<005), and no significant change was found in serum IL-10 concentrations in ABWR-L subgroup(P>005); the serum TNF-α con-centration was significantly decreased at 1 h after the end of CPB, and the serum IL-6 concentration was de-creased at 6 and 24 h after the end of CPB in ABWR-M subgroup(P<005); no significant difference was found in the serum concentrations of TNF-α, IL-6 or IL-10 at each time point after the end of CDB in AB-WR-S subgroup(P<005). Conclusion With prolongation of the time courses of CPB, the efficacy of autologous blood withdrawal-reinfusion in inhibiting inflammatory responses of patients undergoing cardiac surgery is more significant.
