Cost-utility analysis of trastuzumab deruxtecan versus trastuzumab emtansine in the second-line treatment for HER2-positive metastatic breast cancer / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of trastuzumab deruxtecan（T-DXd） versus trastuzumab emtansine （T-DM1） in the second-line treatment of HER2-positive metastatic breast cancer， and to provide a basis for the selection of clinical medication regimen and medical and health decisions. METHODS Based on the clinical trial DESTINY-Breast03， a partitioned survival model was constructed， with a cycle of 3 weeks as the simulation of patients’ lifetime. The incremental cost-effectiveness ratio （ICER） was calculated by using quality-adjusted life years （QALY） as output indicators， and sensitivity analysis was used to verify the robustness of the basic analysis results； the cost-effectiveness of the second-line treatment for HER2-positive metastatic breast cancer was compared between T-DXd and T-DM1. RESULTS Under the premise of taking 3 times China’s per capita gross domestic product （GDP） in 2022 as the willingness-to-pay threshold （257 094 yuan/QALY）， the T-DXd group also needed to pay more cost compared with T-DM1 group while obtaining incremental utility （0.69 QALYs）， and the ICER value was 1 850 478.40 yuan/QALY. The results of univariate sensitivity analysis showed that progression-free survival state utility value， T-DXd price， cost discount rate were factors that had a great influence on ICER value， but these parameters could not flip the basic analysis results within a reasonable range. In the probability sensitivity analysis， when the threshold of willingness-to-pay rose to 1 500 400 yuan/QALY， the probability of economic activity was 50% in the T-DXd regimen. The results of the scenario analysis also verified the robustness of the original research results. CONCLUSIONS Under the premise of 3 times China’s per capita GDP as the WTP threshold， compared with T-DM1， T-DXd is not cost-effective in the second-line treatment of HER2-positive metastatic breast cancer.

Quantitative evaluation for payment policy of diagnosis-related groups in China based on PMC index model / 中国药房

OBJECTIVE To quantitatively evaluate the existing payment policies of diagnosis-related groups （DRGs）in China ， so as to provide reference for the formulation and improvement of policies. METHODS Totally 58 documents related to DRGs payment issued by the national and provincial medical security bureaus from 2017 to 2022 were processed by text mining method. PMC index evaluation model of DRGs payment policy was established. Nine typical DRGs payment policies were quantitatively evaluated and analyzed by 10 primary variables and 40 secondary variables. RESULTS Among the 9 policies，5 were excellent and 4 were acceptable. The average score of PMC index was 6.882. Generally ，there was still room for improvement because of the acceptable level. By comparing the two representative policies ，it was found that the main reasons was a lack of consideration in terms of supervision and management ，incentives and constraints when facing policy changes ，reason of the lower level of urban development. CONCLUSIONS Although DRGs payment policy in China is basically perfect ，there is still a lot of room for improvement in terms of extending the time limit of the policy ，summarizing and spreading the successful experience of pilot cities.

Pharmacoeconomic evaluation of additional use of daratumumab in the treatment of transplant-ineligible newly diagnosed multiple myeloma / 中国药房

OBJECTIVE To evaluate the econ omical efficiency of daratumumab combined with lenalidomide and dexamethasone （D-Rd） regimen versus lenalidomide and dexamethasone （Rd） regimen alone in the treatment of transplant- ineligible newly diagnosed multiple myeloma （TNE-NDMM）. METHODS From the perspective of China ’s health system ，a partitioned survival model with three health states of progression free survival ，disease progression and death was established by using the published MAIA test data and relevant literature data. The model cycle was 28 days and the simulation time limit was 20 years. The incremental cost-effectiveness ratio （ICER）was calculated using quality-adjusted life years （QALY）as the output index. Sensitivity analysis was performed for key parameters. RESULTS The results of basic analysis showed that the ICER of D-Rd regimen versus Rd regimen was 2 719 038.08 yuan/QALY，far exceeding 3 times of GDP per capita in 2021（242 928 yuan）. The results of single factor sensitivity analysis showed that cost discount rate ，progression-free survival utility value ，utility discount rate，the cost of daratumumab and lenalidomide had a greater impact on ICER. Probabilistic sensitivity analysis suggested that the probability of economic advantage of D-Rd regimen was always 0 within the WTP range of 0-1 200 000 yuan. CONCLUSIONS Compared with Rd regimen ，D-Rd regimen has no cost-effectiveness advantage for the treatment of TNE-NDMM under the WTP of 3 times GDP per capita of China .

Cost-utility analysis of sintilimab combined with chemotherapy in first-line treatment of advanced or recurrent non-small cell lung cancer / 中国药房

OBJECTIVE From the perspective o f China ’s h ealth service system ，to ev aluate the cost-effectiveness of sintilimab combined with chemotherapy in the first-line treatment of advanced or recurrent non-small cell lung cancer （NSCLC），so as to provide reference for the selection of clinical medication plan and medical and health decision-making. METHODS Based on the ORIENT-11 study data ，a partitioned survival model was established ，and the model period was 21 days to simulate the death of 99％ of the patients. Using quality-adjusted life years （QALY）as an output indicator ，the cost-effectiveness of sintilimab combined with chemotherapy （trial group ）versus chemotherapy alone （control group ）in the first-line treatment of advanced or recurrent NSCLC was evaluated. Cost and utility were discounted using 5％ discount rate ；sensitivity analysis and scenario analysis were used to verify the robustness of the underlying analysis results. RESULTS Under the premise that 3 times of the per capita gross domestic product （GDP）of China in 2020 was used as the threshold of willingness-to-pay （WTP），the patients in the trial group obtained more utility （0.482 QALY）and also spent nearly twice as much as the control group. The incremental cost-effectiveness ratio（ICER）was 334 974.41 yuan/QALY. Univariate sensitivity analysis showed that progression-free survival status utility value ， pemetrexed price ，utility discount rate ，cost discount rate and sintilimab price had a greater impact on ICER. The results of probability sensitivity analysis showed that when the WTP threshold was 3 times of China ’s per capita GDP in 2020，the probability of the trial group ’s plan being cost-effective was 6.5％. The results of the scenario analysis verified the robustness of the underlying analysis results. CONCLUSIONS On the premise of taking 3 times of China ’s per capita GDP in 2020 as the WTP threshold ， sintilimab combined with chemotherapy is not cost-effective for first-line treatment of advanced or recurrent NSCLC compared with chemotherapy alone.

Transcranial direct current stimulation reconstructs diminished thalamocortical connectivity during prolonged resting wakefulness: a resting-state fMRI pilot study.

Reductions in the alertness and information processing capacity of individuals due to sleep deprivation (SD) were previously thought to be related to dysfunction of the thalamocortical network. Previous studies have shown that transcranial direct current stimulation (tDCS) can restore vigilance and information processing after SD. However, the underlying neural mechanisms of this phenomenon remain unclear. The purpose of this study was to investigate the neurocognitive mechanisms of tDCS following SD, by comparing changes in the brain network, especially the thalamocortical network, after tDCS and sham stimulation following 24 h of SD. Sixteen healthy volunteers were tested in a sham-controlled, randomized crossover design experiment. Resting-state functional magnetic resonance imaging was conducted during resting wakefulness and again after either active tDCS or sham stimulation to the right dorsolateral prefrontal cortex (1.0 mA, 20 min) immediately following 24 h of SD. Seed-based correlations and graph theory analysis were used to determine functional connectivity within the brain thalamocortical network. When tDCS was used, the functional connectivity of the thalamus with the temporal lobe and left caudate was higher than that when the sham stimulation was used. Analysis using graph theory showed that compared with sham stimulation, tDCS administration was associated with a significant improvement in not only the number of connections but also the global efficiency of the thalamus itself. Our study reveals a modulation of the activity of the intrinsic thalamus networks after tDCS. The effects may help explain earlier reports of improvements in the cognitive performance after anodal-tDCS.

MIME-Mitosis instead of meiosis and its application in crop apomixis / 生物工程学报

Apomixis has been widely concerned because of its great potential in heterosis fixation. Artificial apomixis is an important direction of current apomixis research. Mitosis instead of Meiosis (MIME) produces diploid gametes that is identical with the maternal genetic composition and is a key step in the artificial creation of apomixes. This paper reviews the occurrence of MIME and its application in crop apomixis and the problems encountered, in an aim to provide reference for expanding the application of MIME in crop apomixis.

Research progress of Ahmed glaucoma valve implantation in the treatment of neovascular glaucoma / 中华实验眼科杂志

Neovascular glaucoma (NVG) is a kind of devastating secondary glaucoma characterized by neovascularization in iris and anterior chamber angle,which often results in loss of vision.The current standard of treatment includes retinal ablation and control of enhanced intraocular pressure with drugs and surgical therapy.There are a lot of surgical therapies of NVG,while the prognosis of these therapies are not satisfactory as most of them would be effected by different kinds of complications.Ahmed glaucoma valve implantation (AGVI) is one of the main treatments means being widely used with less postoperative complications,such as shallow anterior chamber,low intraocular pressure.Failure of AGVI mainly caused by fiber hyperplasia and neovascularization.AGVI combined with anti-fibrosis therapy and anti-vascular endothelial growth factor (VEGF) therapy might be a promising method to promote surgical outcomes.It has been shown that AGVI combined with anti-VEGF drugs can improve the success rate of surgery.Besides,some researchers found that AGVI with intraoperative application of anti-fibrosis drugs,such as mitomycin C,sustained-release anti-fibrosis drugs can improve the prognosis of surgery in neovascular glaucoma patients.The progress of research on anti-fibrosis and anti-VEGF treatment combined with Ahmed glaucoma valve implantation was discussed in this review.

Levels of aqueous and serum VEGF, TGF-β1 ,IL-6 in neovascular glaucoma eyes / 中华实验眼科杂志

Background Neovascular glaucoma (NVG) is a refractory disease characterized by neovascularization,and its pathogenesis mechanism is still unelucidated.Researches showed that muhicytokins and inflammatory factors are associated with neovascularization,however,the correlation of these factors with NVG worth attention.Objective This study was to detect the vescular endothelial growth factor (VEGF),transforming growth factor β1 (TGF-β1) and interleukin-6 (IL-6) levels in aqueous humor and plasma in NVG eyes and its significance.Methods A prospective cases-controlled study was performed under the approval of Ethic Committee of Shanghai East Hospital and informed consent of patients.Eight eyes of 8 NVG patients,10 eyes of 10 primary open angle glaucoma (POAG) patients and 10 eyes of age-related cataract (ARC) patients were entrolled in Shanghai East Hospital from May,2014 to March,2015.The periphery blood of 3-4 ml was collected from all the patients to prepare 0.3-0.4 ml serum,and 0.1-0.2 ml aqueous humor was collected during the surgery from each eye.The aqueous and serum levels of VEGF,TGF-β1 and IL-6 were measured by ELISA.Results The aqueous humor and plasma VEGF concentrations in NVG patients were (2 769.85 ± 390.88) pg/ml and (529.93 ± 95.20) pg/ml,respectively,which were higher than (208.12 ± 58.59) pg/ml and (219.28 ± 24.44) pg/ml in POAG patients as well as (158.88 ±12.35) pg/ml and (172.82±31.91)pg/ml in ARC patients,with significant differences among the three groups (aqueous:F=433.80,P＜0.01;plasma:F=103.84,P＜0.01).The levels of TGF-β1 in aqueous humor and plasma from NVG patients were (157.94±113.00)pg/ml and (3 895.78±2 318.00)pg/ml,showing significant increases in comparison with (54.48±35.58) pg/ml and (2 196.13±1 185.39) pg/ml in the POAG patients or (47.98±17.69) pg/ml and (1937.28±933.27) pg/ml in the ARC patients (aqueous:F =7.88,P＜0.01;plasma:F =4.18,P＜0.05).The concentration of IL-6 in aqueous humor and plasma were (234.87±41.64) pg/ml and (26.97±8.19) pg/ml from NVG patients,with considerable elavation in comparison with (38.97± 19.06)pg/ml and (19.54±5.11)pg/ml in the POAG patients or (29.48±14.61) pg/ml and (18.50±3.57) pg/ml in the ARC patients (aqueous:F =166.27,P＜0.01;plasma:F=5.59,P＜0.05).Conclusions The aqueous and plasma VEGF,TGF-β1 and IL-6 are considerably higher in NVG patients than those in POAG patients and ARC patients,suggesting that these cytokines participate in the pathogenesis and development of the NVG and probably are treating target of NVG.

Mental health status of relative donors versus unrelated donors before and after hematopoietic stem cell collection / 中国组织工程研究

BACKGROUND:Currently, hematopoietic stem celltransplantation mainly depends on unrelated donors. Mental state of the unrelated donors is very important to ensure the successful celltransplantation. OBJECTIVE:To compare mental and physical health status of relative and unrelated donors during the hematopoietic stem cellcol ection. METHODS:We compared the mental (Symptom Checklist-90) and physical (temperature, breath, pulse, and blood pressure) health status of relative and unrelated donors at admission, 1 day before cellcol ection, and 1-2 days after cellcol ection.RESULTS AND CONCLUSION:At admission, there was no difference in the mental health status of relative and unrelated donors (P>0.05), while the scores on Symptom Checklist-90 were significantly higher in the unrelated donors than the relative donors, including total score, forced, depression, anxiety, hostility, and fear (P<0.05). The physical signs were steady in the unrelated and relative donors, but the difference in breath and systolic blood pressure was of great significance before and after cellcol ection in the two groups. These findings indicate that during cellcol ection, the unrelated donors exhibit heavier mental load than the relative donors, and psychological counseling and health guidance are necessary.

Comparison of the immunotherapy of the CIK cell, LAK cell and PBLS cell mediated by anti-EGFR/anti-CD3 bispecific antibody on the mice borne human gastric cancer / 肿瘤研究与临床

ObjectiveTo investigate the effect of the immunotherapy of CIK cell, LAK cell and PBLS cell mediated by anti-EGFR/anti-CD3 bispecific antibody (BsAb) respectively on the mice borne human gastric cancer and provide experimental evidence for therapeutic strategy in treating gastric cancer. Methods The mAbs of anti-CD3 and anti-EGFR were cross-linked to prepare the BsAb by chemical synthesis. The experimental therapy on the mice borne SGC7901 human gastric cancer was performed,and then the comparisons of the curative activity among the CIK group, LAK group and PBLS group were conducted in vivo. ResultsThe mean tumor reduction rate of the administration of CIK cells directed by anti-EGFR/anti-CD3 BsAb was(64.9±7.7)％ and higher than those of LAK cells or PBLS targeted by anti-EGFR/anti-CD3 BsAb [(43.5±8.2) ％ and (39.7±6.5) ％] (P ＜ 0.05).The mean tumor weight of the administration of CIK cells directed by anti-EGFR/anti-CD3 BsAb was (473.9±37.7) mg at the end of therapy and was lower than those of LAK cells or PBLS targeted by anti-EGFR/anti-CD3 BsAb [(764.6±88.3) mg and (829.1±104.4) mg](P ＜ 0.05). ConclusionThe CIK cell mediated by anti-EGFR/anti-CD3 BsAb could have better curative effect than other effector cells on gastric cancer in vivo.

Study on the influence of c-myc in normal gastric cell line / 肿瘤研究与临床

Objective To investigate the influence of c-myc on the growth, proliferation, apoptosis,invasion and cell cycle of the gastric line HFE145. Methods The cDNA of c-myc was subcloned into a constitutive vector pcDNA3.1 followed by transfection in HFE145 by using liposome. Then stable expression clones (HFE-myc) were selected. The apoptosis and cell cycles were detected using flow cytometry. The growth and proliferation were analyzed by making cell growth curves and colony formation assay respectively. The ability of invasion were tested using cell migration assay. Results HFE-myc group grew faster than HFE145and HFE-pc. The cell counts of HFE-myc in five of seven days were more than those of others significantly (P＜0.05). There was no difference between the two control group. Cell cycle analysis showed that HFE-myc group proliferated faster, mean proportion of cells in G2-M was about 25 % and higher significantly (P ＜0.05)than those of the two control groups. Results of colony formation assay showed that the mean colony formation rate of HFE-myc was 0.27 and higher than those of the control groups(P ＜0.05). The results of cell migration assay suggested that the cell migration rate of HFE-myc was not higher significantly than those of the control groups (P ＞0.05). Conclusion c-myc can promote the growth, proliferation. It can increase the proportion of cells in division stage, so promote the division. But it have little influence on the invasion of cells.