Sources appointment and health risks of PM2.5-bound trace elements in a coastal city of southeastern China.

To gain a comprehensive understanding of sources and health risks of trace elements in an area of China with high population densities and low PM2.5 concentrations, 15 trace elements (Al, K, Ca, Ti, V, Cr, Mn, Fe, Ni, Cu, Zn, As, Sn, Ba, Pb) in PM2.5 were monitored from December 2020 to November 2021 in a representative city, Xiamen. The concentrations of trace elements in Xiamen displayed an obvious seasonal variation and were dominated by K, Fe, Al, Ca and Zn. Based on Positive Matrix Factorization analysis, source appointment revealed that the major sources of trace elements in Xiamen were traffic, dust, biomass and firework combustion, industrial manufacture and shipping emission. According to health risk assessment combined with the source appointment results, it indicated that the average noncarcinogenic risk was below the threshold and cancer risk of four hazardous metals (Cr, Ni, As, Pb) exceeded the threshold (10-6). Traffic-related source had almost half amount of contribution to the health risk induced by PM2.5-bound trace elements. During the dust transport period or Spring Festival period, the health risks exceeded an acceptable threshold even an order of magnitude higher, suggesting that the serious health risks still existed in low PM2.5 environment at certain times. Health risk assessment reminded that the health risk reduction in PM2.5 at southeastern China should prioritize traffic-related hazardous trace elements and highlighted the importance of controlling vehicles emissions in the future.

Cost-Effectiveness Analysis of Relmacabtagene Autoleucel for Relapsed or Refractory Large B-Cell Lymphoma in China.

OBJECTIVES: Relmacabtagene autoleucel (relma-cel) was recently approved in China for treating relapsed or refractory large B-cell lymphoma (r/r LBCL). We conducted a cost-effectiveness analysis from the perspective of Chinese healthcare system. METHODS: A mixture-cure model was developed to project life-years (LYs), quality-adjusted LYs (QALYs), and overall direct cost with a lifetime horizon for patients with r/r LBCL treated with relma-cel versus salvage chemotherapy. Patient-level data from RELIANCE trial and published data from Collaborative Trial in Relapsed Aggressive Lymphoma extension study were used to inform the model. The incremental cost-effectiveness ratio (ICER) was estimated and cost-effectiveness was evaluated at the willingness-to-pay threshold of 3 times the national gross domestic product per capita. RESULTS: The model projected that treatment with relma-cel was associated with incremental gains of 5.11 LYs and 5.26 QALYs compared with salvage chemotherapy at an increased cost of ¥1 067 430 (∼$154 152), resulting in an ICER of ¥203 137 (∼$29 435) per QALY. The model was most sensitive to the uncertainty around the estimated cure rate. The ICER of relma-cel was within the willingness-to-pay threshold in the base case and the probability of relma-cel treatment being considered cost-effective was approximately 74%. CONCLUSIONS: Compared with salvage chemotherapy, treatment with relma-cel for r/r LBCL in patients who have failed at least 2 lines of systemic therapy is within the cost-effective range from the perspective of Chinese healthcare system and represents a good use of healthcare resources.

Highly sensitive detection of thyroglobulin based on sandwich-type electrochemical immunoassay.

As a dimeric protein, thyroglobulin (Tg) is an important biomarker for different thyroid cancer (DTC), so designing effective method to detect Tg is of great significance. In this work, by preparing ß-cyclodextrin (CD) functionalized carbon nanotubes (CNTs) nanohybrid (CD-CNTs) as carrier to immobilize primary antibody (Ab1) of Tg, assembling sulfydryl ferrocene (Fc) and secondary antibody (Ab2) on the surface of nanogold (Au) as signaling amplifier (Ab2-Au-Fc), a simple and sensitive sandwich-type electrochemical immunoassay (STEM) of Tg was designed herein for the first time. In brief, CNTs show large surface area and conductivity, while CD offers superior host-guest recognition capability that can bound with Ab1; meanwhile, Fc probe can offer stable electrochemical signal that is proportionable to the concentration of Tg. Under the optimum conditions, the proposed STEM platform shows excellent sensing results for Tg detection: a considerable low analytical detection (0.5 ng mL-1) and wide linearity (2 to 200 ng mL-1), suggesting the designed STEM platform offers potential real applications for detect Tg.

One-pot synthesis of copper nanocluster/Tb-MOF composites for the ratiometric fluorescence detection of Cu2.

The increasing degradation of ecosystems due to heavy metal residues has led to environment and food contamination, prompting the development of convenient platforms for monitoring heavy metals. Here, a new dual-emission fluorescent sensor CuNCs@Tb@UiO-66-(COOH)2 for the detection of copper ions (Cu2+ ) has been synthesized using one-pot encapsulation of Tb(III) and glutathione-stabilized copper nanoclusters (CuNCs) into metal-organic frameworks (MOFs) UiO-66-(COOH)2 . In this ratiometric sensor, the fluorescence intensity of Tb3+ decreased significantly upon the addition of Cu2+ , whereas that of CuNCs showed good stability, together with an apparent colour change. Therefore, ratiometric fluorescence detection of Cu2+ can be accomplished by measuring the ratio of the fluorescence intensity at the 450 nm (F450 ) wavelength of CuNCs to the 548 nm (F548 ) emission of Tb3+ in the fluorescence spectra of the CuNCs@Tb@UiO-66-(COOH)2 suspension. Moreover, the obtained fluorescent probe showed good results in the detection of actual samples. This work can provide the basis of method for the exploration of ratiometric fluorescence and visual sensors of trace pollutants analysis in complicated samples.

Detrimental effects of microplastic exposure on normal and asthmatic pulmonary physiology.

Concerns that airborne microplastics (MP) may be detrimental to human health are rising. However, research on the effects of MP on the respiratory system are limited. We tested the effect of MP exposure on both normal and asthmatic pulmonary physiology in mice. We show that MP exposure caused pulmonary inflammatory cell infiltration, bronchoalveolar macrophage aggregation, increased TNF-α level in bronchoalveolar lavage fluid (BALF), and increased plasma IgG1 production in normal mice. MP exposure also affected asthma symptoms by increasing mucus production and inflammatory cell infiltration with notable macrophage aggregation. Further, we found co-labeling of macrophage markers with MP incorporating fluorescence, which indicates phagocytosis of the MP by macrophages. A comparative transcriptomic analysis showed that MP exposure altered clusters of genes related to immune response, cellular stress response, and programmed cell death. A bioinformatics analysis further uncovered the molecular mechanism whereby MP stimulated production of tumor necrosis factor and immunoglobulins to activate a group of transmembrane B-cell antigens, leading to the modulation of cellular stress and programmed cell death in the asthma model. In summary, we show that MP exposure had detrimental effects on the respiratory system in both healthy and asthmatic mice, which calls for urgent discourse and action to mitigate environmental microplastic pollutants.

TNF­α treatment increases DKK1 protein levels in primary osteoblasts via upregulation of DKK1 mRNA levels and downregulation of miR­335­5p.

Elucidation of the underlying mechanisms governing osteogenic differentiation is of significant importance to the improvement of therapeutics for bone­related inflammatory diseases. Tumor necrosis factor­α (TNF­α) is regarded as one of the major agents during osteogenic differentiation in an inflammatory environment. miR­335­5p post­transcriptionally downregulates the Dickkopf WNT signaling pathway inhibitor 1 (DKK1) protein level by specifically binding to the DKK1 3'UTR and activating Wnt signaling. The role of miR­335­5p in TNF­α­induced post­transcriptional regulation of DKK1 remains to be elucidated. In the present study, the mRNA and protein levels of DKK1 and the level of miR­335­5p were determined in MC3T3­E1 cells and the primary calvarial osteoblasts treated with or without TNF­α. The role of NF­κB signaling in TNF­α­induced post­transcriptional regulation of DKK1 was also evaluated. The present study determined that although TNF­α treatment exhibited cell­specific effects on DKK1 mRNA expression, the stimulation of TNF­α time­ and concentration­dependently upregulated the protein levels of DKK1. In primary calvarial osteoblasts, the decreased miR­335­5p level induced by TNF­α­activated NF­κB signaling served an important role in mediating the post­transcriptional regulation of DKK1 by TNF­α treatment. In MC3T3­E1 cells, the post­transcriptional regulation of DKK1 by TNF­α treatment was more complicated and involved other molecular signaling pathways in addition to the NF­κB signaling. In conclusion, TNF­α treatment served an important role in the post­transcriptional regulation of DKK1 expression, which requires further investigation. The results of the present study not only provided new insights into the regulatory effects of miR­335­5p on osteogenic differentiation in an inflammatory microenvironment, but may also promote the development of potential therapeutic strategies for the treatment of bone­related inflammatory diseases.

Relationship between the site of thrombosis and the prevalence of pulmonary embolism in acute lower extremity deep venous thrombosis.

OBJECTIVE: Lower extremity deep venous thrombosis (LEDVT) is common and can lead to pulmonary embolism (PE). Currently, the mechanism of how LEDVT causes PE is unclear. The aim of this study was to explore the relationship between the thrombus sites and PE in LEDVT patients. METHODS: A retrospective study that included the medical data of 3101 patients aged >18 years who were diagnosed with LEDVT by duplex ultrasound was performed at The First Affiliated Hospital of Wenzhou Medical University from 2008 to 2017. The clinical information of the patients was collected. According to the thrombosis sites, the patients were divided into three groups. We determined the cumulative prevalence and prevalence rate of PE between the groups and used Cox proportional hazard regression models, which were stratified on matched sets, to calculate the hazard ratios (HRs) for all of the outcomes of interest. We focused on the relationship of proximal or isolated distal LEDVT with PE and also analyzed the relationship of the left side or right side of LEDVT with PE. RESULTS: A total of 1629 (52.5%) patients had left LEDVT (group 1), 912 (29.4%) patients had right LEDVT (group 2), and 560 (18.1%) patients had bilateral LEDVT (group 3). The rate of PE was higher in group 2 than in group 1, although there were more patients suffering from LEDVT in group 1 than in group 2 (P < .001). The patients with proximal LEDVT in group 3 exhibited a greater risk of PE compared with those with isolated distal LEDVT (adjusted HR, 2.79; 95% confidence interval, 1.42-5.49). We also observed that the proportion of patients with proximal LEDVT who were receiving treatment was much higher than that of patients with distal LEDVT (P < .05). The patients with right LEDVT had a higher risk of PE than the patients with left LEDVT (adjusted HR, 1.60; 95% confidence interval, 1.15-2.21), and the patients with right LEDVT had more comorbidities, such as malignant neoplasms, hypertension, and diabetes (P < .001). CONCLUSIONS: Patients with proximal bilateral LEDVT had a higher likelihood for development of PE than did patients with distal LEDVT, which may be associated with inadequate therapy for proximal bilateral LEDVT. PE was more likely to develop with right-sided LEDVT because these patients had more comorbidities in our study.

Cost-effective analysis of clopidogrel versus aspirin for high risk patients with established peripheral arterial disease in China.

Objective: To assess the cost-effectiveness of clopidogrel versus aspirin for high risk patients (pre-existing symptomatic atherosclerosis or multi-vascular territory involvement) with established peripheral arterial disease (PAD) for secondary prevention of atherothrombotic events in a Chinese setting.Methods: A Markov model with a lifetime horizon was developed from the perspective of the national healthcare system in China. The primary outputs are quality adjusted life years (QALYs), direct medical costs, and the incremental cost-effectiveness ratios (ICERs). Clinical efficacy data were obtained from the CAPRIE trial. Drug acquisition cost, other direct medical costs, and utilities were from pricing records and the literature. One-way sensitivity analysis and probabilistic sensitivity analysis (PSA) were conducted to test the robustness of the model on all parameters.Results: In patients with pre-existing atherosclerosis, 2 years of treatment with clopidogrel and aspirin would yield total QALYs of 8.776 and 8.576 at associated costs of ¥18,777 ($2,838) and ¥12,302 ($1,859), respectively, resulting in an ICER of ¥32,382 ($4,893) per QALY gained. In patients with PVD, secondary prevention with the same drugs would expect to lead to total QALYs of 8.836 and 8.632 at associated costs of ¥18,518 ($2,798) and ¥12,041 ($1,820), respectively, resulting in a corresponding ICER of ¥31,743 ($4,797) per QALY gained. The results were most sensitive to the discount rate for future outcomes and costs. The PSA indicated that the probability of clopidogrel being cost-effective was 100% at the willingness-to-pay threshold of 3-times GDP.Conclusions: Secondary prevention with clopidogrel is an attractive cost-effective option compared with aspirin for high risk patients with established PAD from the perspective of the national healthcare system in Chinese settings.

Radiofrequency Catheter Ablation Versus Cryoballoon Ablation in the Treatment of Paroxysmal Atrial Fibrillation: A Cost-effectiveness Analysis in China.

PURPOSE: The aim of this study was to evaluate the cost-effectiveness of radiofrequency catheter ablation (RFCA) compared with cryoballoon (CB) ablation in the treatment of patients with paroxysmal atrial fibrillation (PAF) from the payer's perspective in China. METHODS: We constructed a cohort model, combining a 12-month decision-tree model with a lifetime Markov state-transition model, in a hypothetical cohort of patients with drug-refractory PAF managed with either RFCA or CB ablation, to compare the cost-effectiveness of the 2 procedures. Data related to clinical outcomes and costs in this model were obtained from a retrospective 12-month follow-up study in patients in China and from related literature. The incremental cost-effectiveness ratio (ICER) over a 10-year time period was calculated and compared against the willingness-to-pay (WTP) threshold. We used a 1-way sensitivity analysis and a probabilistic sensitivity analysis (PSA) to access the structural uncertainty and the parameter uncertainty, respectively. FINDINGS: Over a 10-year time horizon, the total costs per patient of RFCA and CB ablation were ¥98,164.04 (US $15,339.57; €13,058.94) and ¥107,542.37 ($16,805.07; €14,306.55), respectively, and quality-adjusted life-years (QALYs) gained were 5.47 and 5.43, respectively. The ICER ratio was -¥224,365.01 (-$35,060.32; -€29,847.68) per QALY, indicating that RFCA is associated with greater QALYs and lower costs than CB ablation. The 1-way sensitivity analysis demonstrated that the model results were most sensitive to the odds ratio of the atrial fibrillation recurrence within 12 months in the RFCA group versus the CB ablation group, the cost of RFCA, and the perioperative stroke risk with RFCA. According to the results of the PSA, RFCA was associated with a high probability of being cost-effective (99.48%) compared with CB ablation at a WTP threshold of ¥161,940 ($25,305.50; €21,543.17) per QALY. IMPLICATIONS: Our analysis indicates that RFCA is cost-saving compared with CB ablation in the treatment of patients with PAF in China, based on better QALYs and lower costs over a 10-year time horizon, from the payer's perspective.

Clopidogrel Versus Aspirin for the Treatment of Acute Coronary Syndrome After a 12-Month Dual Antiplatelet Therapy: A Cost-effectiveness Analysis From China Payer's Perspective.

PURPOSE: Monotherapy with either aspirin or clopidogrel is recommended for long-term use after discontinuation of dual-antiplatelet therapy (DAPT) for acute coronary syndrome (ACS) management after percutaneous coronary intervention (PCI). The present study is to evaluate the cost-effectiveness of clopidogrel versus aspirin after 12-month DAPT for patients with ACS who underwent PCI in China. METHODS: A 2-part model was developed to estimate the cost-effectiveness of clopidogrel compared with aspirin. The short-term part was a decision tree that included health states such as myocardial infarction (MI), stroke, MI and stroke, cardiovascular death, and death from other causes with a treatment horizon of 1 year (base case), 2 years or 3 years after 12-month DAPT. Major bleeding was included. The long-term (lifetime) part was a Markov model that included different health states such as MI, after MI, stroke, after stroke, and death. Drug acquisition cost and other direct medical costs were based on pricing records, literature, and expert panels. Clinical outcomes and utilities were based on literature. The model output included incremental cost-effectiveness ratio of quality-adjusted life-years (QALYs) and total costs per patient. Both 1-way sensitivity analysis and probabilistic sensitivity analysis (PSA) were conducted. FINDINGS: In the base-case scenario, the total costs of the treatment with clopidogrel and aspirin were ¥12,590 ($1849/€1590) and ¥10,642 ($1563/€1344), respectively; the total QALYs of the 2 patient populations were 9.7341 and 9.6894, respectively. The incremental cost-effectiveness ratio of ¥43,593 ($6402/€5515) per QALY gained was lower than 3 times of gross domestic product (GDP) per capita in China (¥161,940, $23,786/€20,449). Both 1-way sensitivity analysis and PSA confirmed the robustness of the results. PSA results indicated that clopidogrel was cost effective versus aspirin in 80.5% of the simulations, considering >3 times the GDP per capita as the threshold. Results in other scenarios (clopidogrel or aspirin for 2 or 3 years after 12-month DAPT) also indicated that clopidogrel was more cost effective than aspirin for patients with ACS after 12-month DAPT. IMPLICATIONS: Compared with aspirin monotherapy, clopidogrel monotherapy for 1 year after 12-month DAPT was cost effective for patients with ACS who underwent PCI in China. Furthermore, when the duration of clopidogrel the monotherapy extended up to 3 years, clopidogrel was still cost effective compared with aspirin. The study was limited by lack of high-quality efficacy data among the Chinese population.

Pharmacoeconomic analysis for pemetrexed as a maintenance therapy for NSCLC patients with patient assistance program in China.

OBJECTIVE: This study is to evaluate the costs, clinical efficacy, and social benefits of a patient assistance program (PAP) implemented by the China Primary Healthcare Foundation for the use of pemetrexed as a first-line non-squamous non-small cell lung cancer (NSCLC) maintenance therapy in China. METHODS: A survival analysis was conducted on the clinical data of 1,366 patients who participated in the PAP. The progression-free survival (PFS) and median maintenance treatment cycle of pemetrexed were analyzed. A 36-month Markov model from a payer's perspective was constructed to analyze the cost and effectiveness associated with the PAP for pemetrexed. The inputs of the model were sourced from the PAP clinical database and published literature. The study estimated the incremental quality adjusted life-years (QALYs) (pemetrexed plus best supportive care [BSC] vs BSC only), the cost saving of the PAP, the impact on the percentage of catastrophic health expenditures (CHE), and poverty headcount ratio (HCR). RESULTS: The median of PFS and maintenance treatment cycles were 187 days and five cycles (total nine cycles, which included four cycles of induction therapy), respectively. The pemetrexed plus BSC treatment with PAP resulted in an additional 0.12 QALYs over BSC only. The total cost was $48,034.46 and $96,191.57 for the patients who had or had not joined the PAP in 3 years, respectively. Compared to the patients without PAP, the percentage of CHE and HCR with PAP was reduced from 98.39% to 19.91% and 66.98% to 4.89%, respectively, indicating that the PAP substantially decreased the number of patients who had CHE and fallen into poverty. CONCLUSION: The study concluded that the pemetrexed PAP generated noticeable clinical and economic benefits to society and to patients. The program also increased patients' compliance with chemotherapy by allowing patients, for whom the pemetrexed treatment was unaffordable, to continue to receive it.