Cost-effectiveness analysis of serplulimab in combination with cisplatin plus 5-fluorouracil chemotherapy compared to cisplatin plus 5-fluorouracil chemotherapy as first-line treatment for advanced or metastatic esophageal squamous cell carcinoma in China.

Background: This study evaluated the cost-effectiveness of serplulimab plus chemotherapy versus chemotherapy alone in treating advanced/metastatic esophageal squamous cell carcinoma (ESCC) within the Chinese health care system. Methods: A partitioned survival model based on ASTRUM-007 trial patient characteristics was developed. Efficacy, safety, and medical/economic data were obtained from the trial and real-world clinical practice. Costs, quality-adjusted life years (QALY), and incremental cost-effectiveness ratios (ICERs) were calculated for both treatment strategies. Sensitivity, subgroup, and scenario analyses were performed to assess the uncertainty impact. Results: Serplulimab combined with chemotherapy yielded an ICER of US$ 53,538.27/QALY. Deterministic sensitivity analysis identified patient survival and serplulimab price as influential parameters. Probabilistic sensitivity analysis showed a 47.33% probability of cost-effectiveness at a willingness-to-pay (WTP) threshold of US$ 53,541/QALY and 0.05% at three times China's GDP per capita. Subgroup analysis revealed that patients with a programmed death-ligand 1 (PD-L1) expression combined positive score (CPS) ⩾10 had a lower hazard ratio (0.59) and ICER (US$ 29,935.23/QALY), with a 95.36% probability of cost-effectiveness. Scenario analysis demonstrated that the drug donation discount policy significantly increased the likelihood of cost-effective serplulimab-chemotherapy combinations in Jiangsu, Fujian, and Guangdong at 99.99%, 99.90%, and 94.16%, respectively. Conclusion: Compared to chemotherapy alone, serplulimab combined with chemotherapy is currently not a cost-effective first-line treatment for advanced/metastatic ESCC in China. However, as serplulimab plus chemotherapy regimens evolve and price competition among programmed death 1 (PD-1) inhibitors intensifies, this combination may become a cost-effective treatment option.

Assessing Serplulimab's Value in Treating Advanced Esophageal Cancer in China In China, esophageal cancer patients often need chemotherapy due to late diagnosis. Serplulimab, an expensive new treatment, is not cost-effective when combined with chemotherapy for most patients. However, for specific patient groups with a PD-L1 expression CPS ⩾ 10, it is both effective and affordable. This finding helps health care leaders create better pricing strategies.

Cost-Effectiveness Analysis of Tislelizumab Plus Chemotherapy as First-Line Treatment for Advanced or Metastatic Esophageal Squamous Cell Carcinoma in China.

Background: Tislelizumab plus chemotherapy improved overall survival compared to chemotherapy alone, while maintaining an acceptable level of safety. But it's still unclear which strategy is the most cost-effective. The objective of the study was to compare the cost-effectiveness of tislelizumab plus chemotherapy as first-line therapy for patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) versus chemotherapy alone. Methods: A partitioned survival model with three states was constructed based on the RATIONALE-306 trial. The model's time horizon was ten years, and its cycle was three weeks. Only direct medical costs were considered from the healthcare perspective in China. Calculations were performed on total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). One-way sensitivity and probabilistic sensitivity analysis (PSA) were performed to determine the uncertainty regarding model parameters. Results: Tislelizumab plus chemotherapy provided 1.35 QALYs for $26,450.77, while chemotherapy alone provided 0.89 QALY for $16,687.15. Compared to chemotherapy alone, tislelizumab had an ICER of $21,062.09/QALY. At the threshold of three times the Chinese GDP per capita ($38,253/QALY), the PSA indicated that tislelizumab had a 96.4% likelihood of being designated cost-effective. At the threshold of 1.5 times the Chinese GDP per capita ($19,126.5/QALY), the PSA indicated that tislelizumab had a probability of 48.7% of being designated cost-effective. Conclusion: Tislelizumab plus chemotherapy as the first treatment for patients with advanced or metastatic ESCC may be a cost-effective option compared to chemotherapy alone at 3 times Chinese GDP per capita.

Individualized treatment decision model for inoperable elderly esophageal squamous cell carcinoma based on multi-modal data fusion.

BACKGROUND: This research aimed to develop a model for individualized treatment decision-making in inoperable elderly patients with esophageal squamous cell carcinoma (ESCC) using machine learning methods and multi-modal data. METHODS: A total of 189 inoperable elderly ESCC patients aged 65 or older who underwent concurrent chemoradiotherapy (CCRT) or radiotherapy (RT) were included. Multi-task learning models were created using machine learning techniques to analyze multi-modal data, including pre-treatment CT images, clinical information, and blood test results. Nomograms were constructed to predict the objective response rate (ORR) and progression-free survival (PFS) for different treatment strategies. Optimal treatment plans were recommended based on the nomograms. Patients were stratified into high-risk and low-risk groups using the nomograms, and survival analysis was performed using Kaplan-Meier curves. RESULTS: The identified risk factors influencing ORR were histologic grade (HG), T stage and three radiomic features including original shape elongation, first-order skewness and original shape flatness, while risk factors influencing PFS included BMI, HG and three radiomic features including high gray-level run emphasis, first-order minimum and first-order skewness. These risk factors were incorporated into the nomograms as independent predictive factors. PFS was substantially different between the low-risk group (total score ≤ 110) and the high-risk group (total score > 110) according to Kaplan-Meier curves (P < 0.05). CONCLUSIONS: The developed predictive models for ORR and PFS in inoperable elderly ESCC patients provide valuable insights for predicting treatment efficacy and prognosis. The nomograms enable personalized treatment decision-making and can guide optimal treatment plans for inoperable elderly ESCC patients.

Genome-wide identification of GH9 gene family and the assessment of its role during fruit abscission zone formation in Vaccinium ashei.

KEY MESSAGE: The genomic location and stage-specific expression pattern of GH9 genes reveal their critical roles during fruit abscission zone formation in Vaccinium ashei. Glycosyl hydrolase family 9 (GH9) cellulases play a crucial role in both cellulose synthesis and hydrolysis during plant growth and development. Despite this importance, there is currently no study on the involvement of GH9-encoding genes, specifically VaGH9s, in abscission zone formation of rabbiteye blueberries (Vaccinium ashei). In this study, we identified a total of 61 VaGH9s in the genome, which can be classified into 3 subclasses based on conserved motifs and domains, gene structures, and phylogenetic analyses. Our synteny analysis revealed that VaGH9s are more closely related to the GH9s of Populus L. than to those of Arabidopsis, Vitis vinifera, and Citrus sinensis. In silico structural analysis predicted that most of VaGH9s are hydrophilic, and localized in cell membrane and/or cell wall, and the variable sets of cis-acting regulatory elements and functional diversity with four categories of stress response, hormone regulation, growth and development, and transcription factor-related elements are present in the promoter sequence of VaGH9s genes. Transcriptomic analysis showed that there were 22 differentially expressed VaGH9s in fruit abscission zone tissue at the veraison stage, and the expression of VaGH9B2 and VaGH9C10 was continuously increased during fruit maturation, which were in parallel with the increasing levels of cellulase activity and oxidative stress indicators, suggesting that they are involved in the separation stage of fruit abscission in Vaccinium ashei. Our work identified 22 VaGH9s potentially involved in different stages of fruit abscission and would aid further investigation into the molecular regulation of abscission in rabbiteye blueberries fruit.

Cost-effectiveness analysis of toripalimab plus chemotherapy versus chemotherapy alone for advanced non-small cell lung cancer in China.

Background: Toripalimab is the first domestic anti-tumor programmed death 1 antibody marketed in China. The CHOICE-01 trial (identifier: NCT03856411) demonstrated that toripalimab plus chemotherapy can significantly improve the clinical outcomes of advanced non-small cell lung cancer (NSCLC) patients. However, whether it is cost-effective remains unknown. Given the high cost of combination therapy, a cost-effectiveness analysis of toripalimab plus chemotherapy (TC) versus chemotherapy alone (PC) for the first-line treatment of patients with advanced NSCLC is required. Methods: A partitioned survival model was adopted to predict the course of disease in advanced NSCLC patients on TC or PC from the perspective of the Chinese healthcare system over a 10-year horizon. The survival data were obtained from the CHOICE-01 clinical trial. Cost and utility values were obtained from local hospitals and kinds of literature. Based on these parameters, the incremental cost-effectiveness ratio (ICER) of TC vs. PC was measured, and one-way sensitivity analyses, probabilistic sensitivity analyses (PSA), and scenario analyses were performed to assess the robustness of the model. Results: In the base case, TC was associated with an incremental cost of $18510 and an incremental quality-adjusted life year (QALY) of 0.57 compared with PC, resulting in an ICER of $32237/QALY which was lower than the willingness to pay (WTP) threshold ($37654/QALY), TC was cost-effective. The health utility value of progression-free survival, the price of toripalimab, and the cost of best supportive care were factors that significantly influenced the ICER, but no change in any of them could change the model result. TC showed a 90% probability of being a cost-effective option at a WTP threshold of $37,654/QALY. In the 20 and 30-year time horizons, the results remained unchanged and TC remained cost-effective when the second-line treatment was switched to docetaxel. Conclusion: At a WTP threshold of $37,654 per QALY, TC was cost-effective compared to PC for patients with advanced NSCLC in China.

Investigating the Mechanisms Underlying the Low Irradiance-Tolerance of the Economically Important Seaweed Species Pyropia haitanensis.

Pyropia haitanensis, one of the most economically and ecologically important seaweed species, is often exposed to persistent or transient low irradiance (LI), resulting in limited yield and quality. However, the mechanisms mediating P. haitanensis responses to LI are largely unknown. In this study, LI-tolerant (LIT) and LI-sensitive (LIS) P. haitanensis strains were compared regarding their physiological and transcriptomic changes induced by 1 and 4 days of LI (5 µmol photons/m2·s). The results indicated that the inhibition of photomorphogenesis and decreases in photosynthesis and photosynthetic carbon fixation as the duration of LI increased are the key reasons for retarded blade growth under LI conditions. A potential self-amplifying loop involving calcium signaling, phosphatidylinositol signaling, reactive oxygen species signaling, and MAPK signaling may be triggered in blades in response to LI stress. These signaling pathways might activate various downstream responses, including improving light energy use, maintaining cell membrane stability, mitigating oxidative damage, to resist LI stress. Additionally, the LIT strain maintained transcriptional homeostasis better than the LIS strain under LI stress. Specifically, photosynthesis and energy production were relatively stable in the LIT strain, which may help to explain why the LIT strain was more tolerant to LI stress than the LIS strain. The findings of this study provide the basis for future investigations on the precise mechanisms underlying the LI stress tolerance of P. haitanensis.

Cost-effectiveness of toripalimab plus chemotherapy for advanced esophageal squamous cell carcinoma.

BACKGROUND: Toripalimab is an immune checkpoint inhibitor (ICI) against programmed death ligand 1 (PD-L1). It has been approved for advanced esophageal squamous cell carcinoma (ESCC) as the first-line treatment due to significantly improved progression-free survival (PFS) and overall survival (OS) in the JUPITER-06 trial. AIM: This study aimed to compare the cost-effectiveness between toripalimab plus chemotherapy and placebo plus chemotherapy from the perspective of the Chinese health system. METHOD: The study developed a 3-year partitioned survival model to assess costs and outcomes in two treatment groups with or without toripalimab. The critical indicator was the incremental cost-effectiveness ratio (ICER). Scenario and sensitivity analyses were performed to evaluate the robustness of the findings and identify the parameters with the greatest impact on cost-effectiveness. RESULTS: In the base case analysis, the incremental effectiveness and cost of toripalimab plus chemotherapy versus placebo plus chemotherapy were 0.26 quality-adjusted life year (QALYs) and $11,254.84, respectively, resulting in an ICER of $43,405.09/QALY, higher than the 2021 willingness-to-pay threshold in China ($37,658.70/QALY). The results were sensitive to the utility of PFS, the incidence of neutropenia in the toripalimab group, and the cost of toripalimab. The toripalimab plus chemotherapy group was cost-effective only if the price of toripalimab decreased by more than 40%. CONCLUSION: Adding toripalimab to chemotherapy was not cost-effective in patients with advanced ESCC in China.

Regional convergence analysis of sustainable innovation efficiency in European Union countries.

Sustainable innovation strategies have been taken very seriously by the European Union (EU), which aims to reduce energy consumption and environmental pollutants emissions. For the sake of testing the sustainable performance of EU countries empirically, this research evaluates the sustainable innovation efficiency (SIE) of EU countries through a DEA-SBM model and analyzes the convergence trends of the EU regions by convergence analysis. The results show that the EU has attached great importance to sustainable innovation efficiency, indicating that the EU makes a concerted effort in technological innovation, energy saving, and environmental protection. Significant differences exist in SIE among EU regions, even though the southern region has the highest efficiency. In addition, there are distinct convergence trends in regional sustainable innovation efficiency. Control variables have significant impacts on the convergence of SIE in the EU regions. Furthermore, policymakers are also provided with useful decision support for regional sustainable innovation, energy conservation, and emission reduction policies.

Economic Value of Fosaprepitant-Containing Regimen in the Prevention of Chemotherapy-Induced Nausea and Vomiting in China: Cost-Effectiveness and Budget Impact Analysis.

Objective: The purpose of this study was to evaluate the cost-effectiveness and budget impact of fosaprepitant (FosAPR)-containing regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) among patients receiving high emetogenic chemotherapy (HEC) from the Chinese payer's perspective. Methods: A decision tree model was established to measure the 5-day costs and health outcomes between the APR-containing regimen (aprepitant, granisetron, and dexamethasone) and FosAPR-containing regimen (fosaprepitant, granisetron, and dexamethasone). Clinical data were derived from a randomized, double-blind controlled trial on Chinese inpatients who received HEC. Quality-adjusted life-years (QALYs) were used to estimate the utility outcomes and the incremental cost-effectiveness ratio (ICER) was calculated to assess the economics of FosAPR. A static budget impact model was developed to assess the impact of FosAPR as a new addition to the National Reimbursement Drug List (NRDL) on the medical insurance fund within 3 years in Nanjing, China. Results: Compared with APR, FosAPR had a mean health-care savings of ¥121.56 but got a reduction of 0.0001815 QALY, resulting in an ICER of ¥669926.19 per QALY. Deterministic sensitivity analysis revealed that the cost of APR was the most influential factor to the ICER. The cost of FosAPR and the complete control rate of the delayed period also had a high impact on the results. According to the probabilistic analysis, the acceptability of FosAPR was more than 80% when the Chinese willingness-to-pay (WTP) was ¥215,999. FosAPR would lead to a 3-year medical insurance payment increase of ¥1.84 million compared with ¥1.49 million before FosAPR entered NRDL in Nanjing. The total budget increased with a cumulative cost of ¥694,829 and covered an additional 341 patients who benefited from FosAPR in Nanjing. Deterministic sensitivity analysis showed that the model of budget impact analysis was stable. Conclusion: FosAPR had a similar treatment effect to APR but was cost-effective in China at the current WTP threshold. The total budget of medical insurance payments of Nanjing slightly increased year by year after the inclusion of FosAPR. Its inclusion in the NRDL would be acceptable and also expand the coverage of patients who benefited from FosAPR.

Impact of public health insurance coverage of novel anticancer medication on medical expenditure and patient affordability in a provincial medical centre of China: a propensity score-matching analysis with the quasi-experimental design.

INTRODUCTION: Little is known about the impact of the government's efforts in having novel anticancer medicines covered by the public health insurance system in China. This study targeted the above policy implemented in Fujian province in 2017, analysed the policy impact on the medical expenditure of cancer treatment and patient affordability based on the clinical data of Fujian provincial medical centre. METHODS: The study included 253 human epidermal growth factor receptor 2-positive patients with breast cancer who completed at least one course of trastuzumab treatment extracted from the hospital health information system of the provincial medical centre of Fujian. We adopted the propensity score-matching method to mimic a quasi-experimental design to estimate the impact of the public health insurance coverage policy on all the indicated patients with a before-after comparison of the total breast cancer-associated direct medical expenditures for a standard course of treatment or maintenance treatment and the proportionate patient out-of-pocket (OOP) expenditure based on the real clinical data. RESULTS: We found evidence of an association between the public health insurance coverage of novel breast cancer medication and the reductions of the medical expenditure by US$18661.02 (95% CI 13 836.57 to 28 201.45), and the proportionate patient OOP expenditure by 24% (95% CI0.20 to 0.27). The medical expenditure and the proportionate patient OOP expenditure might be generally reduced. CONCLUSIONS: The coverage of innovative antibreast cancer medicines by the public health insurance was found to be associated with a reduction of the medical expenditure and share of patient OOP expenditure for cancer treatment of the indicated patients. Patients with lower ability-to-pay did not benefit well from the coverage policy. To maximise the welfare of the public health insurance coverage of novel anticancer medication, the study called for strengthened health insurance benefit packages of the rural patient and the patient enrolled in the urban and rural resident health insurance programme, who might have lower ability-to-pay and need more support from the public security system.

How government health insurance coverage of novel anti-cancer medicines benefited patients in China - a retrospective analysis of hospital clinical data.

BACKGROUND: China started to cover novel medicines for the treatment of major cancers, such as trastuzumab for breast cancer by the government health insurance programs since 2016. Limited data have been published on the use of cancer medications and little is known about how government health insurance coverage of novel anti-cancer medicines benefited patients in the real world. This study aimed to generate evidence to inform the health security authorities to optimize the government health insurance coverage of novel anti-cancer medicines as a more inclusive and equal policy, through which each of the needed patient can get access to the novel anti-cancer medicines regardless of the ability to pay. METHODS: The study targeted one of the government health insurance newly covered novel medicines for breast cancer and the breast cancer patients. The analyses were based on the data collected from one tertiary public hospital in Fujian province of China. We conducted interrupted time series analysis with a segmented regression model and multivariate analyses with a binary logistic regression model to analyze the impact of the government health insurance coverage on medicines utilization and the determinants of patient's medication choice. RESULTS: The average proportion of patients who initiated medication with novel medicines increased from 37.4% before the government health insurance coverage to 69.2% afterwards. Such an increase was observed in all patient sub-groups. The monthly proportion of patients who initiated medication with novel medicines increased sharply by 18.3 % (95 %CI,10.4-34.0 %, p = 0.01) in September 2017, the afterwards trend continuously increased (95 %CI,1.03-3.60, p = 0.02). The critical determinants of patient's medication choice were mostly connected with the patient's health insurance benefits packages. CONCLUSIONS: The government health insurance coverage of novel anti-breast-cancer medicines benefited the patients generally. The utilization of novel medicines such as trastuzumab continuously increased. The insurance coverage benefited well the patients in the high-risk age groups. However, rural patients, patients enrolled in the "resident program", and patients from low-income residential areas and non-local patients benefited less from this policy. Improving the benefits package of the low-income patients and the "resident program" beneficiary would be of considerable significance for a more inclusive and equal health insurance coverage of novel anti-cancer medicines.

The Cost-Effective Preparation of Green Fluorescent Carbon Dots for Bioimaging and Enhanced Intracellular Drug Delivery.

Doxorubicin entrapped carbon dots (DOX-CDs) were prepared for bioimaging and enhanced intracellular drug delivery. The CDs were synthesized via the hydrothermal method using citrate and urea under 200 °C for 1 h. Then, DOX was successfully conjugated on the CDs via physicochemical interactions. The DOX-CDs exhibited good crystal structure, remarkable aqueous stability, excellent photoluminescence property, and a high quantum yield of 93%. The fluorescent images revealed that the DOX-CDs could be readily taken up by the cancer cells for cell labeling. Furthermore, endo-lysosomal pH-assisted DOX release behavior was observed from DOX-CDs, and the cytotoxicity of DOX-CDs was confirmed by the MTS assay against H0-8910 ovarian cancer cells. In addition, the CDs indicated bright fluorescent signal in the animal imaging test and demonstrated low toxicity after administration for 7 and 21 days. Therefore, the prepared CDs could be a promising imaging probe for biomedical imaging and intracellular drug delivery.

Quantitative assessment of Pulmonary Alveolar Proteinosis (PAP) with ultra-dose CT and correlation with Pulmonary Function Tests (PFTs).

BACKGROUND: The purpose of this study was to investigate whether ultra-low-dose chest computed tomography (CT) can be used for visual assessment of CT features in patients with pulmonary alveolar proteinosis (PAP) and to evaluate the relationship between the quantitative analysis of the ultra-low-dose CT scans and the pulmonary function tests (PFTs). METHODS: Thirty-eight patients (mean [SD] age, 44.47 [12.28] years; 29 males, 9 females) with PAP were enrolled and subjected to two scans each with low-dose CT (reference parameters: 120 kV and 50 mAs) and ultra-low-dose CT (reference parameters, 80 kV, 25 mAs). Images were reconstructed via filtered back projection (FBP) for low-dose CT and iterative reconstruction (IR) for ultra-low-dose CT. All patients underwent PFT. The Visual analysis for ground glass opacity (GGO) is performed. The quantitative CT and PFT results were analyzed by canonical correlations. RESULTS: The mean body mass index (BMI) was 25.37±3.26 kg/m2. The effective radiation doses were 2.30±0.46 and 0.24±0.05 mSv for low-dose and ultra-low-dose CT, respectively. The size-specific dose estimates were 5.81±0.81 and 0.62±0.09 mSv for low-dose and ultra-low-dose CT. GGOs and interlobular septal thickening were observed bilaterally in all patients. The average visual GGO score was lower in the upper field (2.67±1.24) but higher in the middle and lower fields (3.08±1.32 and 3.08±0.97, respectively). The average score for the whole lung was 2.94±1.19. There is a significant correlation between PFTs and quantitative of ultra-low-dose CT (canonical loading = 0.78). CONCLUSIONS: Ultra-low-dose CT has the potential to quantify the lung parenchyma changes of PAP. This technique could provide a sensitive and objective assessment of PAP and has good relation with PFTs. In addition, the radiation dose of ultra-low-dose CT was very low.

Comparison of 3.0T MRI with 3D LAVA sequence and digital subtraction angiography for the assessment of accessory hepatic veins in Budd-Chiari syndrome.

PURPOSE: To compare 3D liver acceleration volume acquisition (LAVA) and digital subtraction angiography (DSA) for evaluating the presence of accessory hepatic veins (AHV) in Budd-Chiari syndrome (BCS). MATERIALS AND METHODS: This was a retrospective study in 228 patients with BCS who underwent 3.0T magnetic resonance imaging (MRI) with the 3D LAVA sequence. Two reviewers noted AHV: openings located in the inferior vena cava (IVC), caliber, and the angle of entering into the IVC. MRI results were compared to DSA. Kappa statistics were calculated to quantify intrareader variability in detecting AHVs. RESULTS: On MRI, 63 patients demonstrated no AHV on LAVA images, 70 had one AHV, 62 had two AHVs, 26 patients had three AHVs, six patients had four AHVs, and one patient had five AHVs (P < 0.05 vs. DSA). The mean caliber of the AHVs was 8.3 ± 4.0 mm compared to 9.9 ± 3.2 for DSA (P < 0.001). Among the 301 AHVs, there were 140 with acute angles (46.5%), 71 with right angles (23.6%), and 90 with obtuse angles (29.8%). The prevalence of AHVs on DSA was 54.8% (125/228), while MRI demonstrated 301 AHVs in 165 patients, for a prevalence of 72.4% (165/228) compared to 54.8% for DSA (P = 0.001). The two methods were concordant in only 116/228 (50.9%) patients. The kappa coefficient demonstrated good intrareader consistency for all documented MRI findings of AHVs (κ = 0.626 for caliber and κ = 0.65 for angles). CONCLUSION: More AHVs were visible on MRI LAVA sequences than on conventional DSA. LEVEL OF EVIDENCE: 4 J. Magn. Reson. Imaging 2017;45:401-409.

Ambient insect pressure and recipient genotypes determine fecundity of transgenic crop-weed rice hybrid progeny: Implications for environmental biosafety assessment.

Transgene introgression into crop weedy/wild relatives can provide natural selective advantages, probably causing undesirable environmental impact. The advantages are likely associated with factors such as transgenes, selective pressure, and genetic background of transgene recipients. To explore the role of the environment and background of transgene recipients in affecting the advantages, we estimated the fitness of crop-weed hybrid lineages derived from crosses between marker-free insect-resistant transgenic (Bt/CpTI) rice with five weedy rice populations under varied insect pressure. Multiway anova indicated the significant effect of both transgenes and weedy rice genotypes on the performance of crop-weed hybrid lineages in the high-insect environment. Increased fecundity was detected in most transgene-present F1 and F2 hybrid lineages under high-insect pressure, but varied among crop-weed hybrid lineages with different weedy rice parents. Increased fecundity of transgenic crop-weed hybrid lineages was associated with the environmental insect pressure and genotypes of their weedy rice parents. The findings suggest that the fitness effects of an insect-resistant transgene introgressed into weedy populations are not uniform across different environments and genotypes of the recipient plants that have acquired the transgene. Therefore, these factors should be considered when assessing the environmental impact of transgene flow to weedy or wild rice relatives.

[Preparation and Assessment of IL1RAP Monoclonal Antibody].

OBJECTIVE: To prepare and identify human monoclonal antibody against IL-1 receptor accessory protein (IL1RAP), which is a new identified surface marker for leukemia stem cells (LSC). METHODS: BALB/c mice were inoculated intraperitoneally with hybridoma cells (3H6E10, 10D8A7) and their ascites were collected. The monoclonal antibody against hu-IL1RAP specifically was purified from ascites, the nondenaturing-PAGE, ELISA and Western blot were used to detect the purity, titer and sensitivity of antibody. RESULTS: Two purified antibodies were obtained and named as 3H6E10 McAb and 10D8A7 McAb, whose purity was 95% and 94% respectively. The titer of two purified monoclonal antibodies was 1 : 81000 and specific conjugation of IL1RAP purified protein and endogenous protein from normal people and leukemia patients with purified antibodies were confirmed. CONCLUSION: The purified monoclonal antibodies which can specifically bind to hu-IL1RAP are successfully prepared, thus providing novel way to effectively clear LSC in the future.

Assessment of renal function in patients with unilateral ureteral obstruction using whole-organ perfusion imaging with 320-detector row computed tomography.

BACKGROUND: Obstructed nephropathy is a common complication of several disease processes. Accurate evaluation of the functional status of the obstructed kidney is important to achieve a good outcome. The purpose of this study was to investigate renal cortical and medullary perfusion changes associated with unilateral ureteral obstruction (UUO) using whole-organ perfusion imaging with 320-detector row computed tomography (CT). METHODOLOGY/PRINCIPLE FINDINGS: Sixty-four patients with UUO underwent whole-organ CT perfusion imaging. Patients were divided into 3 groups, mild, moderate, and severe, based on hydronephrosis severity. Twenty sex- and age-matched patients without renal disease, who referred to abdominal CT, were chosen as control subjects. Mean cortical and medullary perfusion parameters of obstructed and contralateral kidneys were compared, and mean perfusion ratios between obstructed and contralateral kidneys were calculated and compared. Mean cortical or medullary blood flow (BF) and blood volume (BV) of the obstructed kidneys in the moderate UUO and BF, BV, and clearance (CL) in the severe UUO were significantly lower than those of the contralateral kidneys (p < 0.05). The mean cortical or medullary BF of the obstructed kidney in the moderate UUO, and BF, BV, and CL in the severe UUO were significantly lower than those of the kidneys in control subjects (p < 0.05). Mean cortical or medullary BF of the non-obstructed kidneys in the severe UUO were statistically greater than that of normal kidneys in control subjects (p < 0.05). An inverse correlation was observed between cortical and medullary perfusion ratios and grades of hydronephosis (p < 0.01). CONCLUSIONS/SIGNIFICANCE: Perfusion measurements of the whole kidney can be obtained with 320-detector row CT, and estimated perfusion ratios have potential for quantitatively evaluating UUO renal injury grades.

Neural decoding using a parallel sequential Monte Carlo method on point processes with ensemble effect.

Sequential Monte Carlo estimation on point processes has been successfully applied to predict the movement from neural activity. However, there exist some issues along with this method such as the simplified tuning model and the high computational complexity, which may degenerate the decoding performance of motor brain machine interfaces. In this paper, we adopt a general tuning model which takes recent ensemble activity into account. The goodness-of-fit analysis demonstrates that the proposed model can predict the neuronal response more accurately than the one only depending on kinematics. A new sequential Monte Carlo algorithm based on the proposed model is constructed. The algorithm can significantly reduce the root mean square error of decoding results, which decreases 23.6% in position estimation. In addition, we accelerate the decoding speed by implementing the proposed algorithm in a massive parallel manner on GPU. The results demonstrate that the spike trains can be decoded as point process in real time even with 8000 particles or 300 neurons, which is over 10 times faster than the serial implementation. The main contribution of our work is to enable the sequential Monte Carlo algorithm with point process observation to output the movement estimation much faster and more accurately.

Purification and functional assessment of smooth muscle cells derived from mouse embryonic stem cells.

OBJECTIVE: To obtain a pure population of smooth muscle cells (SMC) derived from mouse embryonic stem cells (ESC) and further assess their functions. METHODS: A vector, expressing both puromycin resistance gene (puro(r) ) and enhanced green fluorescent protein (EGFP) gene driven by smooth muscle 22α (SM22α) promoter, named pSM22α-puro(r)-IRES2-EGFP was constructed and used to transfect ESC. Transgenic ESC (Tg-ESC) clones were selected by G418 and identified by PCR amplification of puro(r) gene. The characteristics of Tg-ESC were detected by alkaline phosphatase (ALP) staining, SSEA-1 immunofluorescence and teratoma formation test in vivo. After induction of SMC differentiation by all-trans retinoic acid, differentiated Tg-ESC were treated with 10 µg/mL puromycin for three days to obtain purified SMC (P-SMC). Percentage of EGFP(+) cells in P-SMC was assessed by flow cytometer. Expressions of smooth muscle specific markers were detected by immunostaining and Western blotting. Proliferation, migration and contractility of P-SMC were analyzed by growth curve, trans-well migration assay, and carbachol treatment, respectively. Finally, both P-SMC and unpurified SMC (unP-SMC) were injected into syngeneic mouse to see teratoma development. RESULTS: Tg-ESC clone was successfully established and confirmed by PCR detection of puro(r) gene in its genomic DNA. The Tg-ESC was positive for ALP staining, SSEA-1 staining and formed teratoma containing tissues derived from three germ layers. After retinoic acid induction, large amount of EGFP positive cells outgrew from differentiated Tg-ESC. Three days of puromycin treatment produced a population of P-SMC with an EGFP(+) percentage as high as 98.2% in contrast to 29.47% of unP-SMC. Compared with primary mouse vascular smooth muscle cells (VSMC), P-SMC displayed positive, but lowered expression of SMC-specific markers including SM α-actin and myosin heavy chain (SM-MHC) detected either, by immunostaining, or immunoblotting, accelerated proliferation, improved migration (99.33 ± 2.04 vs. 44.00 ± 2.08 migrated cells/field, P < 0.05), and decreased contractility in response to carbachol (7.75 ± 1.19 % vs. 16.50 ± 3.76 % in cell area reduction, P < 0.05). In vivo injection of unP-SMC developed apparent teratoma while P-SMC did not. CONCLUSIONS: We obtained a pure population of ESC derived SMC with less mature (differentiated) phenotypes, which will be of great use in research of vascular diseases and in bio-engineered vascular grafts for regenerative medicine.