Cost-effectiveness analysis of CYP2C19 genotype-guided antiplatelet therapy for patients with acute minor ischemic stroke and high-risk transient ischemic attack in China.

AIMS: The study aimed to estimate the cost-effectiveness of CYP2C19 genotype-guided antiplatelet therapy using cilostazol and ticagrelor as an alternative to clopidogrel, compared to conventional antiplatelet therapy with clopidogrel and aspirin. METHODS: A 90-day decision tree and 30-year Markov model were employed to assess the costs and quality-adjusted life years (QALYs) of personalized antiplatelet therapy for patients with minor ischemic stroke and high-risk transient ischemic attack, compared to conventional antiplatelet therapy in the Chinese healthcare system. The primary outcome was the incremental cost-effectiveness ratio (ICER). The data sources included clinical trials, published literature, official documents and local prices. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to confirm the robustness of the findings. RESULTS: The base-case analysis indicated that the CYP2C19 genotype-guided antiplatelet strategy was cost-effective, and cilostazol group and ticagrelor group yielded an ICER of 3327.40 US dollars (USD)/QALY and 3426.92 USD/QALY, respectively, which were less than threshold. The one-way sensitivity analysis showed the results were robust, where the most sensitive parameter was the disability distribution in the modified Rankin scale 3-5. The probabilistic analysis showed that the CYP2C19 genotype-guided antiplatelet therapy with either cilostazol or ticagrelor was 100% cost-effective under the willingness-to-pay threshold. CONCLUSIONS: CYP2C19 genotype-guided antiplatelet therapy using cilostazol and ticagrelor as an alternative to clopidogrel appeared to be more cost-effective than conventional antiplatelet therapy for acute minor ischemic stroke and high-risk transient ischemic attack patients over 30 years in China.

Erythrocyte membrane n-3 PUFA are inversely associated with breast cancer risk among Chinese women.

The relationship between erythrocyte membrane n-3 PUFA and breast cancer risk is controversial. We aimed to examine the associations of erythrocyte membrane n-3 PUFA with odds of breast cancer among Chinese women by using a relatively large sample size. A case-control study was conducted including 853 newly diagnosed, histologically confirmed breast cancer cases and 892 frequency-matched controls (5-year interval). Erythrocyte membrane n-3 PUFA were measured by GC. Logistic regression and restricted cubic spline were used to quantify the association between erythrocyte membrane n-3 PUFA and odds of breast cancer. Erythrocyte membrane α-linolenic acid (ALA), docosapentaenoic acid (DPA) and total n-3 PUFA were inversely and non-linearly associated with odds of breast cancer. The OR values (95 % CI), comparing the highest with the lowest quartile (Q), were 0·57 (0·43, 0·76), 0·43 (0·32, 0·58) and 0·36 (0·27, 0·49) for ALA, DPA and total n-3 PUFA, respectively. Erythrocyte membrane EPA and DHA were linearly and inversely associated with odds of breast cancer ((EPA: ORQ4 v. Q1 (95 % CI) = 0·59 (0·45, 0·79); DHA: ORQ4 v. Q1 (95 % CI) = 0·50 (0·37, 0·67)). The inverse associations were observed between ALA and odds of breast cancer in postmenopausal women, and between DHA and oestrogen receptor+ breast cancer. This study showed that erythrocyte membrane total and individual n-3 PUFA were inversely associated with odds of breast cancer. Other factors, such as menopause and hormone receptor status, may warrant further investigation when examining the association between n-3 PUFA and odds of breast cancer.

Relief of Residual Stress in Bulk Thermosets in the Glassy State by Local Bond Exchange.

The covalently cross-linked network gives thermosets superior thermal, mechanical, and electrical properties, which, however, squarely makes the large residual stress that is inevitably induced during preparation hardly relieved in the glassy state. In this work, an incredible reduction in residual stress is successfully achieved in bulk thermosets in the glassy state through introducing highly dynamic thiocarbamate bonds by "click" reactions of thiols and isocyanates. Due to the excellent dynamic behaviors of thiocarbamate bonds, local network rearrangement is achieved through thermal stimulation, while the strong 3D cross-linked network is well maintained. Ultimately, a decrease by 44% in residual stress is detected by simply annealing samples at 30 °C below glass transition temperature (Tg), during which they could well maintain more than 98.4% of the storage modulus. After the annealing, more uniform residual stress distribution is also observed, showing a 32% decline in sample standard deviation. However, the residual stress of epoxy resin, a typical thermoset as a reference, changes little even after annealing at Tg. The results prove it a feasible strategy to reduce residual stress in bulk thermosets in the glassy state by introducing proper dynamic covalent bonds.

Cyclic Dinucleotide-Based Enantioselective Fluorination in Water.

The diverse structures of DNA serve as potent chiral scaffolds for DNA-based asymmetric catalysis, yet in most cases tens to hundreds of nucleotides in DNA hybrid catalysts hinder the deep insight into their structure-activity relationship. Owing to the structural simplicity and design flexibility of nucleotides, nucleotide-based catalysts have been emerging as a promising way to obtain fine structural information and understand the catalytic mechanisms. Herein, we found that a cyclic dinucleotide of cyclic di-AMP (c-di-AMP) and 1,10-phenanthroline copper(II) nitrate (Cu(phen)(NO3)2) are assembled to a c-di-AMP-based catalyst (c-di-AMP/Cu(phen)(NO3)2), which could fast achieve enantioselective fluorination in water with 90-99% yields and up to 90% enantiomeric excess (ee). The host-guest interaction between c-di-AMP and Cu(phen)(NO3)2 has been proposed mainly in a supramolecular interaction mode as evidenced by spectroscopic techniques of ultraviolet-visible, fluorescence, circular dichroism, and nuclear magnetic resonance. Cu(phen)(NO3)2 tightly binds to c-di-AMP with a binding constant of 1.7 ± 0.3 × 105 M-1, and the assembly of c-di-AMP/Cu(phen)(NO3)2 shows a modest rate enhancement to carbon-fluorine bond formations as supported by kinetic studies.

Serum levels of n-3 PUFA and colorectal cancer risk in Chinese population.

Circulating n-3 PUFA, which integrate endogenous and exogenous n-3 PUFA, can be better used to investigate the relationship between n-3 PUFA and disease. However, studies examining the associations between circulating n-3 PUFA and colorectal cancer (CRC) risk were limited, and the results remained inconclusive. This case­control study aimed to examine the association between serum n-3 PUFA and CRC risk in Chinese population. A total of 680 CRC cases and 680 sex- and age-matched (5-year interval) controls were included. Fatty acids were assayed by GC. OR and 95 % CI were calculated using multivariable logistic regression after adjustment for potential confounders. Higher level of serum α-linolenic acid (ALA), docosapentaenoic acid (DPA), DHA, long-chain n-3 PUFA and total n-3 PUFA were associated with lower odds of CRC. The adjusted OR and 95 % CI were 0·34 (0·24, 0·49, Pfor trend < 0·001) for ALA, 0·57 (0·40, 0·80, Pfor trend < 0·001) for DPA, 0·48 (0·34, 0·68, Pfor trend < 0·001) for DHA, 0·39 (0·27, 0·56, Pfor trend < 0·001) for long-chain n-3 PUFA and 0·31 (0·22, 0·45, Pfor trend < 0·001) for total n-3 PUFA comparing the highest with the lowest quartile. However, there was no statistically significant association between EPA and odds of CRC. Analysis stratified by sex showed that ALA, DHA, long-chain n-3 PUFA and total n-3 PUFA were inversely associated with odds of CRC in both sexes. This study indicated that serum ALA, DPA, DHA, long-chain n-3 PUFA and total n-3 PUFA were inversely associated with odds of having CRC in Chinese population.

Cost-effectiveness of preimplantation genetic testing for aneuploidy for women with subfertility in China: an economic evaluation using evidence from the CESE-PGS trial.

BACKGROUND: There are a large number of infertile couples in China, but its treatment is notoriously expensive and not currently covered by insurance. The utility of preimplantation genetic testing for aneuploidy as an adjunct to in vitro fertilization has been debated. OBJECTIVE: To investigate the cost-effectiveness of preimplantation genetic testing for aneuploidy (PGT-A) versus conventional technology in in vitro fertilization (IVF) from the perspective of the healthcare system in China. METHODS: Following the exact steps in the IVF protocol, a decision tree model was developed, based on the data from the CESE-PGS trial and using cost scenarios for IVF in China. The scenarios were compared for costs per patient and cost-effectiveness. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to confirm the robustness of the findings. MAIN OUTCOME MEASURES: Costs per live birth, Costs per patient, Incremental cost-effectiveness for miscarriage prevention. RESULTS: The average costs per live birth of PGT-A were estimated as ¥39230.71, which is about 16.8% higher than that of the conventional treatment. Threshold analysis revealed that PGT-A would need to increase the pregnancy rate of 26.24-98.24% or a cost reduction of ¥4649.29 to ¥1350.71 to achieve the same cost-effectiveness. The incremental costs per prevented miscarriage was approximately ¥45600.23. The incremental cost-effectiveness for miscarriage prevention showed that the willingness to pay would be ¥43422.60 for PGT-A to be cost-effective. CONCLUSION: The present cost-effectiveness analysis demonstrates that embryo selection with PGT­A is not suitable for routine applications from the perspective of healthcare providers in China, given the cumulative live birth rate and the high costs of PGT­A.

Dumbbell-Shaped Antisense Oligonucleotide Prodrugs Showed Improved Antinuclease Stability and Anticancer Efficacy.

Antisense oligonucleotides (ASONs) have generated widespread interest as antitumor agents. Nevertheless, the utility of natural ASONs is limited due to their rapid degradation by intracellular and extracellular nucleases. In this work, we proposed a novel prodrug-type ASON with a dumbbell conformation and a responsive disulfide switch. A degradation assay showed that the dumbbell-shaped ASON (DS-ASON) exhibited stronger stability against enzymatic degradation compared with that of the linear or single-end looped ASON. The native ASON could dissociate via breakage of the disulfide switch when in the reductive microenvironment of a tumor. In addition, an optimal DS-ASON, L2, displayed robust antitumor activity both in vitro and in vivo. This paper presents a new design of nucleic acid-based therapeutics featuring a conformational change that provides improved stability and biological efficacy.

Single-cell RNA sequencing reveals the heterogeneity and interactions of immune cells and Müller glia during zebrafish retina regeneration.

ABSTRACT: Inflammation plays a crucial role in the regeneration of fish and avian retinas. However, how inflammation regulates Müller glia (MG) reprogramming remains unclear. Here, we used single-cell RNA sequencing to investigate the cell heterogeneity and interactions of MG and immune cells in the regenerating zebrafish retina. We first showed that two types of quiescent MG (resting MG1 and MG2) reside in the uninjured retina. Following retinal injury, resting MG1 transitioned into an activated state expressing known reprogramming genes, while resting MG2 gave rise to rod progenitors. We further showed that retinal microglia can be categorized into three subtypes (microglia-1, microglia-2, and proliferative) and pseudotime analysis demonstrated dynamic changes in microglial status following retinal injury. Analysis of cell-cell interactions indicated extensive crosstalk between immune cells and MG, with many interactions shared among different immune cell types. Finally, we showed that inflammation activated Jak1-Stat3 signaling in MG, promoting their transition from a resting to an activated state. Our study reveals the cell heterogeneity and crosstalk of immune cells and MG in zebrafish retinal repair, and may provide valuable insights into future mammalian retina regeneration.

Serum Saturated Fatty Acids including Very Long-Chain Saturated Fatty Acids and Colorectal Cancer Risk among Chinese Population.

The association between circulating saturated fatty acids (SFAs) including very long-chain SFAs (VLCSFAs) and colorectal cancer (CRC) risk has not been clearly established. To investigate the association between serum SFAs and CRC risk in Chinese population, 680 CRC cases and 680 sex and age-matched (5-year interval) controls were recruited in our study. Serum levels of SFAs were detected by gas chromatography. Unconditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between serum SFAs and CRC risk. Results showed that total SFAs were positively associated with the risk of CRC (adjusted OR quartile 4 vs. 1 = 2.64, 95%CI: 1.47-4.74). However, VLCSFAs were inversely associated with CRC risk (adjusted OR quartile 4 vs. 1 = 0.51, 95%CI: 0.36-0.72). Specifically, lauric acid, myristic acid, palmitic acid, heptadecanoic acid, and arachidic acid were positively associated with CRC risk, while behenic acid and lignoceric acid were inversely associated with CRC risk. This study indicates that higher levels of total serum SFAs and lower levels of serum VLCSFAs were associated with an increased risk of CRC in Chinese population. To reduce the risk of CRC, we recommend reducing the intake of foods containing palmitic acid and heptadecanoic acid such as animal products and dairy products, and moderately increasing the intake of foods containing VLCSFAs such as peanuts and canola oil.

Effects of health qigong exercise on sleep and life quality in patients with drug abuse.

Objective: The aim of this study was to investigate the effect of Health Qigong (HQ) exercise on the subjective and objective sleep quality and the quality of life in male patients with drug abuse who received treatment at a mandatory drug rehabilitation residential institution. Methods: Ninety male patients (mean age, 36.85 ± 8.72 y) were included and randomly divided into the Health Qigong (HQ) group, aerobic exercise (AE) group, or control group. The participants in the HQ and AE groups exercised four times a week for 1 hour per session for 12 weeks, while the control group maintained their original lifestyle. The following parameters were recorded before and after exercise: Pittsburgh Sleep Quality Index (PSQI); SF-36; and total sleep time, sleep efficiency, sleep latency, deep sleep time, deep sleep rate, light sleep time, and light sleep rate using actigraphy. Results: Health Qigong improved the subjective sleep quality, objective sleep quality, and quality of life after a 12-week intervention. Considering the subjective sleep quality, Health Qigong helped improve several aspects of the PSQI, including the overall sleep quality (p < 0.01), sleep latency (p < 0.01), sleep duration (p < 0.01), sleep latency (p < 0.01), sleep disturbance (p < 0.01), and day dysfunction (p < 0.01). In relation to the objective sleep quality, Health Qigong improved the total sleep time (p < 0.01), sleep efficiency (p < 0.01), sleep latency (p < 0.01), deep and light sleep rate (p < 0.01). Considering the quality of life, Health Qigong helped improve the role-physical (p < 0.01), general health (p < 0.01), bodily pain (p < 0.01), and mental health (p < 0.01) aspects of SF-36. Conclusion: Health Qigong may be an effective approach to improve the subjective and objective quality of sleep and life quality of patients with drug abuse.

Evaluating the Price, Availability, and Affordability of Essential Medicines in Primary Healthcare Institutions: A Mixed Longitudinal and Cross-Sectional Study in Jiangsu, China.

Objective: This study aimed to evaluate the price, availability, and affordability of essential medicines in primary healthcare institutions in Jiangsu Province. Methods: A mixed longitudinal and cross-sectional survey was conducted in primary healthcare institutions in Jiangsu based on the adjusted World Health Organization and Health Action International methodology. 45 essential medicines were collected from 30 primary healthcare institutions in Nanjing from 2016 to 2020. We also collected information on these medicines in 70 primary healthcare institutions across seven cities of Jiangsu in 2021. The availability, price, and affordability were compared with matched sets. Differences of availability between years and cities were further compared using Wilcoxon rank-sum test. Results: In Nanjing, the variation was significant of availability during the study period. The MPR was generally decreasing between 2016 and 2020, with the median price ratio (MPR) for lowest-priced generics (LPGs) ranging from 1.20 to 2.53 and originator brands (OBs) substantially above international levels. The median availability of generic medicines increased in 2018 and subsequently stabilized at around 55%, and the availability of originator medicines was low. There were no significant regional differences in prices across the sampled cities in Jiangsu, and the median MPR for LPGs was acceptable (1.23), while the median MPR for OBs was 8.54. The mean availability was different across regions (p < 0.001), being higher in Nanjing (54.67%) and Nantong (56.22%), and lower in northern Jiangsu (about 35%). For LPGs, there was little difference in the proportion of medicines with low availability and high affordability (50.00% for urban residents and 40.48% for rural residents). For OBs, there were more than half of rural residents had low availability and low affordability of medicines (58.82%). Conclusions: In terms of yearly changes, the prices of essential medicines have considerably decreased, and the availability of LPGs has slightly increased. However, the availability of medicines was found to be poor and there were regional differences in the availability and affordability of medicines among metropolitan and rural areas. Policy interventions targeting external factors associated with health resource allocation are essential and possible strategies include effective and efficient government investment mechanisms on primary healthcare.

Impact of the national drug price negotiation policy on the utilization, cost, and accessibility of anticancer medicines in China: A controlled interrupted time series study.

Background: China implemented the national drug price negotiation (NDPN) policy to include 17 innovative anticancer medicines in the national reimbursement drug list in 2018. We aimed to assess the impact of this policy on the utilization, cost, and accessibility of anticancer medicines. Methods: We obtained monthly medicine procurement data from 1039 hospitals from October 2017 to December 2019. We examined changes in availability, utilization, defined daily dose cost (DDDc), and affordability of the medicines using descriptive statistics and controlled interrupted time series analysis, measuring utilization by defined daily doses (DDDs). Cetuximab and raltitrexed were compared separately for the same indication. Results: The mean availability of 17 negotiated anticancer medicines was 28.78% after the NDPN, amounting to an increase of 25.22%. The availability increased by 7.88% (95% confidence interval (CI) = 4.31%, 11.45%, P < 0.001) immediately and by 1.23% (95% CI = 0.81%, 1.64%, P < 0.001) per month after policy implementation. Compared with the control group, the utilization of the medicines increased by 11.44 DDDs (95% CI = 2.42, 20.46, P = 0.014) immediately and by 3.54 DDDs (95% CI = 2.47, 4.60, P < 0.001) per month after policy implementation, while the DDDc decreased by US$109.09 (95% CI = 68.14, 150.05, P < 0.001) immediately and remained stable thereafter. The results on cetuximab and raltitrexed were similar. Availability and utilization differed among regions in east, middle, and west China. Out-of-pocket costs decreased by 17.35 times the catastrophic health expenditures to 1.99 times, but the affordability ratio for 14 negotiated medicines was still greater than 1. Conclusions: The NDPN policy improved the availability, utilization, and affordability of anticancer medicines. China's experience in NDPN provides a reference for other countries. However, the availability and affordability of anticancer medicines still need further improvement.

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.

Cost-Utility Analysis of CYP2C19 Genotype Detection for Selection of Acid-Suppressive Therapy with Lansoprazole or Vonoprazan for Patients with Reflux Esophagitis in China.

BACKGROUND: The cytochrome P450 (CYP) 2C19 genotype has a profound effect on the efficacy of lansoprazole, with less of an influence on vonoprazan. Both are first-choice drugs for the treatment of reflux esophagitis in China. OBJECTIVE: We aimed to estimate the cost-effectiveness of acid-suppressive treatments in Chinese patients with reflux esophagitis over 1 year from the societal perspective. METHODS: We developed a decision-based Markov model with a 4-week cycle to simulate the economic benefits and quality-adjusted life-years between different treatment strategies for patients with reflux esophagitis: universal lansoprazole, universal vonoprazan, and CYP2C19 genotype-guided strategies. The primary outcome was the incremental cost-effectiveness ratio. Data sources were the published literature, clinical trials, documents, and local charges. We used sensitivity analyses to detect the robustness of the findings and explored subgroup analyses and scenario analyses to make further evaluations. RESULTS: Compared to lansoprazole, vonoprazan and the CYP2C19 genotype-guided strategy were not preferable for Chinese patients with reflux esophagitis, with an incremental cost-effectiveness ratio of 222,387.1316 yuan/quality-adjusted life-year and 349,627.5000 yuan/quality-adjusted life-year, respectively. Sensitivity analyses showed the impact factors were the utility scores and the expenditures for the maintenance stage with lansoprazole and vonoprazan. When the willingness-to-pay threshold was 215,484 yuan/quality-adjusted life-year, 46.20% of the reflux esophagitis population was willing to pay for vonoprazan, compared with 8.30% for the CYP2C19 genotype-guided strategies. Vonoprazan and the CYP2C19 genotype-guided strategy were cost effective in the severe reflux esophagitis population, and in the reduction of the price of vonoprazan. CONCLUSIONS: The health economic evaluations revealed that for Chinese patients with reflux esophagitis, vonoprazan and the CYP2C19 genotype-guided strategy were not cost-effective regimens compared with lansoprazole. However, we found that in certain conditions like a reduction in the price of vonoprazan and in patients with severe reflux esophagitis these could be cost-effective.

Sleep disorders as a prospective intervention target to prevent drug relapse.

Objective: The high rate of relapse has become the primary obstacle of drug rehabilitation. In this study, we explored the relationship between sleep disorders and relapse inclination in substance users, as well as the potential mediating mechanisms and corresponding interventions. Methods: A total of 392 male substance users were recruited to complete the questionnaires on sleep disorders, quality of life and relapse inclination. On account of this, 60 participants with sleep disorders were randomly screened and allocated to the intervention and control groups. The former received 12 weeks of Health Qigong aimed at treating sleep disorders, whereas the latter performed their regular production work. Results: Sleep disorders had a positive effect on relapse inclination, quality of life was a potential mediator of this relationship, and 12-week Health Qigong designed to treat sleep disorders improved not only their sleep quality but also their overall quality of life, which in turn reduce the tendency to relapse. Conclusion: Current research not only explores the high-risk factors influencing relapse, but also develops customized intervention strategies, which have theoretical and practical implications for decreasing relapse and increasing abstinence.

Association of dietary n - 3 polyunsaturated fatty acids with breast cancer risk: Serial mediating roles of erythrocyte n - 3 polyunsaturated fatty acids.

Background: Dietary n - 3 polyunsaturated fatty acids (PUFAs) were found to be inversely associated with breast cancer risk; however, the underlying pathways between them remain uncertain. We aimed to explore serial mediatory roles of erythrocyte n - 3 PUFAs in association between dietary n - 3 PUFAs and breast cancer risk. Materials and methods: Using a case-control study, 850 cases and 861 controls completed structured questionnaires with dietary information. Erythrocyte n - 3 PUFAs were measured by gas chromatography. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained using multiple unconditional logistic regression models to examine association between dietary n - 3 PUFAs and breast cancer risk. Mediation analyses with bootstrapping were conducted to investigate indirect effects. Results: Higher intake of dietary ALA, long-chain n - 3 PUFAs and total n - 3 PUFAs was associated with lower risk of breast cancer. The adjusted OR tertile 3 v.1 (95% CI) was 0.70 (0.55, 0.90) for ALA, 0.76 (0.60, 0.97) for long-chain n - 3 PUFAs and 0.74 (0.58, 0.94) for total n - 3 PUFAs, respectively. Mediation analysis showed that erythrocyte long-chain n - 3 PUFAs served as sequential mediators in the relationship between dietary long-chain or total n - 3 PUFAs and breast cancer risk. In particular, erythrocyte long-chain n - 3 PUFAs completely mediated the association between dietary long-chain n - 3 PUFAs and breast cancer risk [indirect effect (95% CI) = -0.982 (-1.529, -0.508)]. The relationship between dietary total n - 3 PUFAs and breast cancer risk was partly mediated by erythrocyte long-chain n - 3 PUFAs [indirect effect (95% CI) = -0.107 (-0.216, -0.014)], accounting for 19.31%. However, the serial mediation model in dietary ALA and risk of breast cancer was not statistically significant [indirect effect (95% CI) = -0.042 (-0.144, 0.049)]. Conclusion: This study highlights the complexity and inaccuracy in using a simple analysis of individual dietary n - 3 PUFAs to examine their associations with breast cancer risk without considering the variety of metabolic processes. Interventions aimed at increasing erythrocyte long-chain n - 3 PUFAs may represent a promising strategy for breast cancer prevention.

Cost-Effectiveness of Pyrotinib Plus Capecitabine versus Lapatinib Plus Capecitabine for the Treatment of HER2-Positive Metastatic Breast Cancer in China: A Scenario Analysis of Health Insurance Coverage.

BACKGROUND: The overexpression of the human epidermal growth factor receptor-2 (HER2) gene is present in 20~25% of breast cancer (BC) patients, contributing to an inferior prognosis. Recent clinical trials showed that pyrotinib has promising antitumor activities and acceptable tolerability for those patients (ClinicalTrials.gov, NCT03080805 and NCT02422199). Therefore, this study aims to assess the cost-effectiveness of pyrotinib plus capecitabine versus lapatinib plus capecitabine for patients with HER2-positive metastatic BC after prior trastuzumab. METHODS: A lifetime-partitioned survival model was established to evaluate health and economic outcomes with different treatment strategies. The primary outcome was the incremental cost-effectiveness ratio (ICER). Data were derived from the published literature, clinical trials, expert opinions, and other local charges. Sensitivity analyses were performed to assess the robustness of the findings. Scenario analyses were developed to make further evaluations. RESULTS: The pyrotinib regimen had significant advantages over the lapatinib regimen after enrolling in the National Reimbursement Drug List (NRDL), with cost savings of USD 15,599.27 and a gain of 0.53 QALYs. Meanwhile, before enrolling in NRDL, the pyrotinib regimen afforded the same QALYs at a higher incremental cost of USD 45,400.64 versus the lapatinib regimen, producing an ICER of USD 85,944.79 per QALY. Scenario analyses yielded similar results. Sensitivity analyses suggested stability in the cost-effectiveness findings. CONCLUSIONS: Compared to lapatinib plus capecitabine, the pyrotinib plus capecitabine enrolled in NRDL is a cost-effective alternative second-line treatment for patients with HER2-positive metastatic BC in China.

Association of dietary intake of n-3 polyunsaturated fatty acids with breast cancer risk in pre- and postmenopausal Chinese women.

OBJECTIVE: This study aimed to evaluate the associations between breast cancer risk and intake of n-3 polyunsaturated fatty acids (PUFAs) and/or n-3 PUFA subclasses in Chinese women, and determine whether these associations varied with menopausal status or clinical characteristics. METHODS: A hospital-based case-control study including 1,589 cases and 1,621 age-frequency-matched controls was conducted. Dietary data were assessed by a validated food frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals were obtained using multiple unconditional logistic regression models after controlling for potential confounders. RESULTS: Higher intake of marine n-3 PUFAs and total n-3 PUFAs was associated with lower risk of breast cancer, with adjusted OR quartile 4 v.1 (95% confidence intervals) of 0.68 (0.55-0.84) and 0.56 (0.42-0.75), respectively. Dietary a-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid were also inversely associated with breast cancer risk, with adjusted ORs (95% confidence intervals) of 0.51 (0.38-0.70), 0.68 (0.55-0.84), 0.68 (0.55-0.85), and 0.76 (0.61-0.94), respectively. In stratified analyses, these inverse associations between risk and dietary n-3 PUFAs were more evident among premenopausal women and women with ER+, PR+ and ER+PR+ tumors. A decreased risk of breast cancer was significantly associated with increasing n-3 PUFA intake in obese/overweight women, but not in women of normal weight. There was a significant interaction between linoleic acid and marine n-3 PUFAs. CONCLUSIONS: High intake of n-3 PUFAs and n-3 PUFA subtypes was associated with a lower risk of breast cancer, especially among premenopausal women and women with ER+ and/or PR+ subtype breast cancer.

Paricalcitol versus Calcitriol + Cinacalcet for the Treatment of Secondary Hyperparathyroidism in Chronic Kidney Disease in China: A Cost-Effectiveness Analysis.

Background: Chronic Kidney Disease (CKD) is a global chronic disease with increasing prevalence in recent years, particularly CKD accompanied by Secondary Hyperparathyroidism (SHPT) leads to reduced quality of life, increased mortality, a considerable economic burden for patients and society. The aim of this study was to investigate the cost-effectiveness analysis of paricalcitol vs. calcitriol + cinacalcet for CKD patients with SHPT in China in 2020. Methods: A Markov model was conducted employing data derived from published literature, clinical trials, official sources, and tertiary public hospital data in China, based on a 10-year horizon from the perspective of the healthcare system. Calcitriol + Cinacalcet was used as the reference group. CKD stage 5 (CKD-5) dialysis patients suffering from SHPT were included in the study. Effectiveness was measured in quality-adjusted life years (QALYs). The discount rate (5%) was applied to costs and effectiveness. Sensitivity analysis was performed to confirm the robustness of the findings. Results: The base case analysis demonstrated that Patients treated with paricalcitol could gain an increase in utility (0.183 QALYs) and require fewer expenditures (6925.612 yuan). One-way sensitivity analysis was performed to showed that impact factors were the price of cinacalcet, the hospitalization costs of patients with paricalcitol and calcitriol, the costs and utilities of hemodialysis and the costs of calcitriol, the costs of paricalcitol regardless of period. Probabilistic simulation analysis displayed when willingness-to-pay was ¥217113, the probability that Paricalcitol was dominant is 96.20%. Conclusion: The results showed that paricalcitol administrated to treat patients diagnosed with Secondary hyperparathyroidism in Chronic Kidney Disease, compared to calcitriol and cinacalcet, might be dominant in China.

Carbon emissions, the industrial structure and economic growth: Evidence from heterogeneous industries in China.

A comprehensive understanding of the relationships among carbon emissions, the industrial structure and economic growth holds great significance for China's transition to a low-carbon economy, industrial structure optimization, and achievement of energy conservation and emission reduction targets. We selected six major industrial sectors (agriculture, industry, construction, transportation, retail and accommodation and other industries) as research objects, introduced the extended STIRPAT decomposition model, Tapio decoupling model and the grey relation analysis to discuss the relationship among the three. Results showed that (i) since 2000, the proportions of value added of agriculture, manufacturing, and transportation are negatively correlated with carbon emissions, while those of construction, retail and accommodation, and other industries are positively correlated with carbon emissions. (ii) The overall economic growth and carbon emissions of these six major industries have experienced the process of decoupling-coupling-decoupling-coupling-decoupling. (iii) The relevance of these six industries to GDP is ranked as follows: transportation > manufacturing > retail andaccommodation > agriculture > construction > other industries. Additionally, accelerating the achievement of a clean energy structure, strengthening the strength and speed of industrial structure adjustment and reducing the dependence on fossil energy are the key steps for China to reach carbon emissions peak goal.