Accountability analysis of health benefits related to National Action Plan on Air Pollution Prevention and Control in China.

China is one of the largest producers and consumers of coal in the world. The National Action Plan on Air Pollution Prevention and Control in China (2013-2017) particularly aimed to reduce emissions from coal combustion. Here, we show whether the acute health effects of PM2.5 changed from 2013 to 2018 and factors that might account for any observed changes in the Beijing-Tianjin-Hebei (BTH) and the surrounding areas where there were major reductions in PM2.5 concentrations. We used a two-stage analysis strategy, with a quasi-Poisson regression model and a random effects meta-analysis, to assess the effects of PM2.5 on mortality in the 47 counties of BTH. We found that the mean daily PM2.5 levels and the SO42- component ratio dramatically decreased in the study period, which was likely related to the control of coal emissions. Subsequently, the acute effects of PM2.5 were significantly decreased for total and circulatory mortality. A 10 µg/m3 increase in PM2.5 concentrations was associated with a 0.16% (95% CI: 0.08, 0.24%) and 0.02% (95% CI: -0.09, 0.13%) increase in mortality from 2013 to 2015 and from 2016 to 2018, respectively. The changes in air pollution sources or PM2.5 components appeared to have played a core role in reducing the health effects. The air pollution control measures implemented recently targeting coal emissions taken in China may have resulted in significant health benefits.

Cancer risks among first-degree relatives of women with a genetic predisposition to breast cancer.

BACKGROUND: Associations between germline alterations in women and cancer risks among their relatives are largely unknown. METHODS: We identified women from 2 Swedish cohorts Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA) and prevalent KARMA (pKARMA), including 28 362 women with genotyping data and 13 226 with sequencing data. Using Swedish Multi-Generation Register, we linked these women to 133 389 first-degree relatives. Associations between protein-truncating variants in 8 risk genes and breast cancer polygenic risk score in index women and cancer risks among their relatives were modeled via Cox regression. RESULTS: Female relatives of index women who were protein-truncating variant carriers in any of the 8 risk genes had an increased breast cancer risk compared with those of noncarriers (hazard ratio [HR] = 1.85, 95% confidence interval [CI] = 1.52 to 2.27), with the strongest association found for protein-truncating variants in BRCA1 and 2. These relatives had a statistically higher risk of early onset than late-onset breast cancer (P = .001). Elevated breast cancer risk was also observed in female relatives of index women with higher polygenic risk score (HR per SD = 1.28, 95% CI = 1.23 to 1.32). The estimated lifetime risk was 22.3% for female relatives of protein-truncating variant carriers and 14.4% for those related to women in the top polygenic risk score quartile. Moreover, relatives of index women with protein-truncating variant presence (HR = 1.30, 95% CI = 1.06 to 1.59) or higher polygenic risk score (HR per SD = 1.04, 95% CI = 1.01 to 1.07) were also at higher risk of nonbreast hereditary breast and ovary cancer syndrome-related cancers. CONCLUSIONS: Protein-truncating variants of risk genes and higher polygenic risk score in index women are associated with an increased risk of breast and other hereditary breast and ovary syndrome-related cancers among relatives.

Investigation of Genetic Alterations Associated With Interval Breast Cancer.

Importance: Breast cancers (BCs) diagnosed between 2 screening examinations are called interval cancers (ICs), and they have worse clinicopathological characteristics and poorer prognosis than screen-detected cancers (SDCs). However, the association of rare germline genetic variants with IC have not been studied. Objective: To evaluate whether rare germline deleterious protein-truncating variants (PTVs) can be applied to discriminate between IC and SDC while considering mammographic density. Design, Setting, and Participants: This population-based genetic association study was based on women aged 40 to 76 years who were attending mammographic screening in Sweden. All women with a diagnosis of BC between January 2001 and January 2016 were included, together with age-matched controls. Patients with BC were followed up for survival until 2021. Statistical analysis was performed from September 2021 to December 2022. Exposure: Germline PTVs in 34 BC susceptibility genes as analyzed by targeted sequencing. Main Outcomes and Measures: Odds ratios (ORs) were used to compare IC with SDC using logistic regression. Hazard ratios were used to investigate BC-specific survival using Cox regression. Results: All 4121 patients with BC (IC, n = 1229; SDC, n = 2892) were female, with a mean (SD) age of 55.5 (7.1) years. There were 5631 age-matched controls. The PTVs of the ATM, BRCA1, BRCA2, CHEK2, and PALB2 genes were more common in patients with IC compared with SDC (OR, 1.48; 95% CI, 1.06-2.05). This association was primarily influenced by BRCA1/2 and PALB2 variants. A family history of BC together with PTVs of any of these genes synergistically increased the probability of receiving a diagnosis of IC rather than SDC (OR, 3.95; 95% CI, 1.97-7.92). Furthermore, 10-year BC-specific survival revealed that if a patient received a diagnosis of an IC, carriers of PTVs in any of these 5 genes had significantly worse survival compared with patients not carrying any of them (hazard ratio, 2.04; 95% CI, 1.06-3.92). All of these associations were further pronounced in a subset of patients with IC who had a low mammographic density at prior screening examination. Conclusions and Relevance: The results of this study may be helpful in future optimizations of screening programs that aim to lower mortality as well as the clinical treatment of patients with BC.

Safety and feasibility study of a novel stent-graft for thoracic endovascular aortic repair: a canine model experiment

Abstract Objective: To evaluate the safety and feasibility of a novel stent-graft for thoracic endovascular aortic repair (TEVAR) in a canine model, 9 adult hybrid dogs were used for the experiment. Methods: All animals were implanted with a novel thoracic aortic stent-graft via femoral artery. Blood sample was collected at pre-operation and 1, 2, 4, 8 and 12 weeks after implantation for hematological examination. Moreover, tissues from randomly selected 4 dogs were subjected to histopathological analysis with the optical microscope after stent-grafts were implanted for 3, 6, 9, and 12 months respectively. The experimental period lasted for more than 2 years. Results: A total of 9 stent-grafts were successfully implanted in the canine thoracic aortas and no migration or deformation occurred. Related indicators of blood routine, inflammatory factors, and immunology changes were not significantly (P>0.05), except the white blood cell (WBC) counts in the first week. Moreover, abnormal morphology was not found in all thoracic aortas via histopathological examination. Additionally, all stent-grafts were patent and did not migrate, and there was no thrombus in the lumens of stent-grafts. Conclusion: The novel thoracic aortic stent-graft made in China was safe and feasible for thoracic endovascular aortic repair in a canine model.