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Ecosystem service assessment and prediction play a crucial role in sustainable regional development and resource management. Liaoning Province, as a typical representative of Northeast China, faces rapid development challenges such as urbanization, industrialization, and agricultural modernization. At the same time, there is an urgent need for a deeper understanding of the evolution trends of its ecosystems and their impact on ecosystem services. This study employed the InVEST-Markov-PLUS model to conduct simulated research on the assessment of past and future ecosystem services and multi-scenario predictions in Liaoning Province. Based on the land-use changes in Liaoning Province from 2000 to 2020, the InVEST model was used to evaluate the spatiotemporal variations in carbon storage, soil conservation, and water yield in the ecosystem services from 2000 to 2020. Additionally, the equivalent factor method was employed to calculate the value of ecosystem services in Liaoning Province during the same period. Furthermore, by integrating the PLUS and Markov models with the actual conditions of Liaoning Province, four land-use development scenarios for 2030 were constructed, including natural development, economic priority, ecological protection, and cropland protection. The land-use distribution and the quantities and values of ecosystem services under these scenarios were simulated. The study revealed the following findingsï¼ â From 2000 to 2020, carbon storage and soil retention in Liaoning Province showed an overall increasing trend, whereas water yield exhibited a fluctuating decrease trend initially, followed by an increase and then another decrease. â¡ Carbon storage and soil retention in Liaoning Province showed higher values in the eastern mountainous areas and western hilly regions, with lower values in the central region. Water yield showed a decreasing trend from east to west. ⢠The value of ecosystem services increased from 547.94 billion yuan to 565.53 billion yuan, with a total increase of 17.58 billion yuan during the study period. All four types of services showed an increase, with cultural services experiencing the fastest change. ⣠In 2030, carbon storage and soil retention in Liaoning Province decreased in all scenarios except for in the ecological protection scenario. Water yield increased only in the cropland protection scenario, whereas it decreased in the other three scenarios. The value of ecosystem services in the study area increased in all scenarios except for in the economic priority scenario.
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The Canadian Congenital Anomalies Surveillance Network was established in 2002 to address gaps in the national surveillance of congenital anomalies (CAs) and support the sustainability of high-quality, population-based, CA surveillance systems within provinces and territories. This paper highlights the methodologies of each local CA surveillance system, noting similarities and variabilities between each system, to contribute to enhanced national CA surveillance efforts.
The Canadian Congenital Anomalies Surveillance Network was established in 2002 under the umbrella of the Canadian Perinatal Surveillance System to support highquality, population-based congenital anomalies surveillance systems in Canada. Each local congenital anomalies surveillance system covers diverse populations and geography, operates under different structures and has varying program maturity. Engagement of every jurisdiction is essential for sustaining local and national CA surveillance. Provincial and territorial CA surveillance systems are uniquely positioned to support public health priorities.
Le Réseau canadien de surveillance des anomalies congénitales a été créé en 2002, dans le cadre du Système canadien de surveillance périnatale, afin de soutenir des systèmes de surveillance des anomalies congénitales de haute qualité et fondés sur la population à l'échelle du Canada. Les systèmes locaux de surveillance des anomalies congénitales couvrent des populations et des zones géographiques diverses, fonctionnent selon des structures différentes et ont une maturité variable. La participation de chaque administration est essentielle pour soutenir la surveillance locale et nationale des anomalies congénitales. Les systèmes provinciaux et territoriaux de surveillance des anomalies congénitales sont particulièrement bien placés pour soutenir les priorités en matière de santé publique.
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Anomalías Congénitas , Vigilancia de la Población , Humanos , Canadá/epidemiología , Anomalías Congénitas/epidemiología , Anomalías Congénitas/diagnóstico , Vigilancia de la Población/métodos , Recién NacidoRESUMEN
BACKGROUND: Maternal obesity is associated with stillbirth, but uncertainty persists around the effects of higher obesity classes. We sought to compare the risk of stillbirth associated with maternal obesity alone versus maternal obesity and additional or undiagnosed factors contributing to high-risk pregnancy. METHODS: We conducted a retrospective cohort study using the Better Outcomes Registry and Network (BORN) for singleton hospital births in Ontario between 2012 and 2018. We used multivariable Cox proportional hazard regression and logistic regression to evaluate the relationship between prepregnancy maternal body mass index (BMI) class and stillbirth (reference was normal BMI). We treated maternal characteristics and obstetrical complications as independent covariates. We performed mediator analyses to measure the direct and indirect effects of BMI on stillbirth through major common-pathway complications. We used fully adjusted and partially adjusted models, representing the impact of maternal obesity alone and maternal obesity with other risk factors on stillbirth, respectively. RESULTS: We analyzed data on 681 178 births between 2012 and 2018, of which 1956 were stillbirths. Class I obesity was associated with an increased incidence of stillbirth (adjusted hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.35-1.78). This association was stronger for class III obesity (adjusted HR 1.80, 95% CI 1.44-2.24), and strongest for class II obesity (adjusted HR 2.17, 95% CI 1.83-2.57). Plotting point estimates for odds ratios, stratified by gestational age, showed a marked increase in the relative odds for stillbirth beyond 37 weeks' gestation for those with obesity with and without other risk factors, compared with those with normal BMI. The impact of potential mediators was minimal. INTERPRETATION: Maternal obesity alone and obesity with other risk factors are associated with an increased risk of stillbirth. This risk increases with gestational age, especially at term.
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Obesidad Materna , Mortinato , Embarazo , Femenino , Humanos , Lactante , Mortinato/epidemiología , Estudios Retrospectivos , Obesidad/epidemiología , Factores de RiesgoRESUMEN
Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.
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Hematogenous metastasis is the main approach for colorectal cancer liver metastasis (CRCLM). However, as the gatekeepers in the tumor vessels, the role of TPCs in hematogenous metastasis remains largely unknown, which may be attributed to the lack of specific biomarkers for TPC isolation. Here, microdissection combined with a pericyte medium-based approach is developed to obtain TPCs from CRC patients. Proteomic analysis reveals that TRP channel-associated factor 2 (TCAF2), a partner protein of the transient receptor potential cation channel subfamily M member 8 (TRPM8), is overexpressed in TPCs from patients with CRCLM. TCAF2 in TPCs is correlated with liver metastasis, short overall survival, and disease-free survival in CRC patients. Gain- and loss-of-function experiments validate that TCAF2 in TPCs promotes tumor cell motility, epithelial-mesenchymal transition (EMT), and CRCLM, which is attenuated in pericyte-conditional Tcaf2-knockout mice. Mechanistically, TCAF2 inhibits the expression and activity of TRPM8, leading to Wnt5a secretion in TPCs, which facilitates EMT via the activation of the STAT3 signaling pathway in tumor cells. Menthol, a TRPM8 agonist, significantly suppresses Wnt5a secretion in TPCs and CRCLM. This study reveals the previously unidentified pro-metastatic effects of TPCs from the perspective of cold-sensory receptors, providing a promising diagnostic biomarker and therapeutic target for CRCLM.
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Neoplasias Colorrectales , Neoplasias Hepáticas , Canales Catiónicos TRPM , Ratones , Animales , Humanos , Pericitos/metabolismo , Proteómica , Sensación Térmica , Neoplasias Colorrectales/genética , Canales Catiónicos TRPM/genética , Canales Catiónicos TRPM/metabolismo , Proteínas de la Membrana/metabolismoRESUMEN
AIMS: Vessel co-option is responsible for tumor resistance to antiangiogenic therapies (AATs) in patients with colorectal cancer liver metastasis (CRCLM). However, the mechanisms underlying vessel co-option remain largely unknown. Herein, we investigated the roles of a novel lncRNA SYTL5-OT4 and Alanine-Serine-Cysteine Transporter 2 (ASCT2) in vessel co-option-mediated AAT resistance. METHODS: SYTL5-OT4 was identified by RNA-sequencing and verified by RT-qPCR and RNA fluorescence in situ hybridization assays. The effects of SYTL5-OT4 and ASCT2 on tumor cells were investigated by gain- and loss-of-function experiments, and those of SYTL5-OT4 on ASCT2 expression were analyzed by RNA immunoprecipitation and co-immunoprecipitation assays. The roles of SYTL5-OT4 and ASCT2 in vessel co-option were detected by histological, immunohistochemical, and immunofluorescence analyses. RESULTS: The expression of SYTL5-OT4 and ASCT2 was higher in patients with AAT-resistant CRCLM. SYTL5-OT4 enhanced the expression of ASCT2 by inhibiting its autophagic degradation. SYTL5-OT4 and ASCT2 promoted vessel co-option by increasing the proliferation and epithelial-mesenchymal transition of tumor cells. Combination therapy of ASCT2 inhibitor and antiangiogenic agents overcame vessel co-option-mediated AAT resistance in CRCLM. CONCLUSION: This study highlights the crucial roles of lncRNA and glutamine metabolism in vessel co-option and provides a potential therapeutic strategy for patients with AAT-resistant CRCLM.
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Neoplasias Hepáticas , ARN Largo no Codificante , Humanos , Alanina , Proteínas Portadoras , Línea Celular Tumoral , Cisteína , Hibridación Fluorescente in Situ , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Proteínas de la Membrana , Proteínas de Transporte de Membrana , ARN Largo no Codificante/genética , SerinaRESUMEN
Colorectal cancer (CRC) is the third most common cause of cancer mortality worldwide. Approximately 40% of CRC patients are KRAS sequence variation, including KRAS G13D mutation (KRASG13D) CRC patients, accounting for approximately 8% of all KRAS mutations in CRC patients and showing little benefit from anti-EGFR therapy. Therefore, there is an urgent need for new and effective anticancer agents in patients with KRASG13D CRC. Here, we identified a natural product, erianin, that directly interacted with purified recombinant human KRASG13D with a Kd of 1.1163 µM, which also significantly improve the thermal stability of KRASG13D. The cell viability assay showed that KRASG13D cells were more sensitive to erianin than KRASWT or KRASG12V cells. In vitro, results showed that erianin suppressed the migration, invasion and epithelial-mesenchymal transition (EMT) of KRASG13D CRC cells. Furthermore, erianin induced ferroptosis, as evidenced by the accumulation of Fe2+ and reactive oxygen species (ROS), lipid peroxidation, and changes in the mitochondrial morphology of KRASG13D CRC cells. Interestingly, we also found that erianin-induced ferroptosis was accompanied by autophagy. Moreover, the occurrence of erianin-induced ferroptosis is reversed by autophagy inhibitors (NH4Cl and Bafilomycin A1) and ATG5 knockdown, suggesting that erianin-induced ferroptosis is autophagy-dependent. In addition, we evaluated the inhibition of tumor growth and metastasis by erianin in vivo using a subcutaneous tumor model and a spleen-liver metastasis model, respectively. Collectively, these data provide novel insights into the anticancer activity of erianin, which is valuable for the further discussion and investigation of the use of erianin in clinical anticancer chemotherapy for KRASG13D CRC.
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Neoplasias Colorrectales , Ferroptosis , Humanos , Proteínas Proto-Oncogénicas p21(ras)/genética , Ferroptosis/genética , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Mutación , AutofagiaRESUMEN
BACKGROUND: This study aims to evaluate the impact of socioeconomic status (SES) on the risk of congenital heart disease (CHD) since previous studies have yielded inconsistent results. METHODS: We conducted a population-based retrospective cohort study, including all singleton live and still births in Ontario hospitals from April 1, 2012, to March 31, 2018. We used linked records from the Better Outcomes Registry & Network Information System, the Canadian Institute for Health Information databases, and the Ontario Marginalization Index (ON_Marg). ON_Marg was estimated at a dissemination area level using Canadian Census 2016 data and categorized into quintiles. Multivariable logistic regression models were performed to examine the relationships between four ON_Marg indices (material deprivation, dependency, ethnic concentration, residential instability), as proxies for maternal SES and the risk of infant CHD. We adjusted for maternal age at birth, assisted reproductive technology, obesity, pre-existing health conditions, substance use during pregnancy, mental health conditions before and during pregnancy, rural residence, and infant's sex in the analysis. RESULTS: Among the cohort of 776,799 singletons, 9,359 infants had a diagnosis of CHD. Of those, 3,069 were severe CHD and 493 cases were single ventricle CHD. The prevalence of all infant CHD types was higher for males relative to females. Compared to mothers living in neighbourhoods with the lowest material deprivation, mothers with highest material deprivation had a 27% (adjusted OR = 1.27; 95% CI: 1.18-1.37) higher odds of having an infant diagnosed with CHD. Mothers living in neighbourhoods with the highest minority ethnic and immigrant concentration tend to have infants with 11% lower odds of CHD (adjusted OR = 0.89; 95% CI: 0.82-0.97) as compared to those living in the least ethnically diverse communities. Maternal dependency and residential stability quintiles were not significantly associated with the risk of CHD. CONCLUSION: Higher maternal material deprivation was associated with increasing odds of infant CHD, whereas neighbourhood minority ethnic concentration was inversely associated with the odds of infant CHD. Our study further confirms that poverty is associated with CHD development. Future investigations might focus on the causal pathways between social deprivation, immigrant status, ethnicity, and the risk of infant CHD.
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Cardiopatías Congénitas , Clase Social , Embarazo , Masculino , Recién Nacido , Femenino , Lactante , Humanos , Ontario/epidemiología , Estudios Retrospectivos , Madres , Cardiopatías Congénitas/epidemiologíaRESUMEN
BACKGROUND: Around 2% of births in Ontario, Canada involve the use of assisted reproductive technology (ART), and it is rising due to the implementation of a publicly funded ART program in 2016. To better understand the impact of fertility treatments, we assessed perinatal and pediatric health outcomes associated with ART, hormonal treatments, and artificial insemination compared with spontaneously conceived births. METHODS: This population-based retrospective cohort study was conducted using provincial birth registry data linked with fertility registry and health administrative databases in Ontario, Canada. Live births and stillbirths from January 2013 to July 2016 were included and followed to age one. The risks of adverse pregnancy, birth and infant health outcomes were assessed by conception method (spontaneous conception, ART - in vitro fertilization and non-ART - ovulation induction, intra-uterine or vaginal insemination) using risk ratios and incidence rate ratios with 95% confidence intervals (CI). Propensity score weighting using a generalized boosted model was applied to adjust for confounding. RESULT(S): Of 177,901 births with a median gestation age of 39 weeks (IQR 38.0-40.0), 3,457 (1.9%) were conceived via ART, and 3,511 (2.0%) via non-ART treatments. There were increased risks (adjusted risk ratio [95% CI]) of cesarean delivery (ART: 1.44 [1.42-1.47]; non-ART: 1.09 [1.07-1.11]), preterm birth (ART: 2.06 [1.98-2.14]; non-ART: 1.85 [1.79-1.91]), very preterm birth (ART: 2.99 [2.75-3.25]; non-ART: 1.89 [1.67-2.13]), 5-min Apgar < 7 (ART: 1.28 [1.16-1.42]; non-ART: 1.62 [1.45-1.81]), and composite neonatal adverse outcome indicator (ART: 1.61 [1.55-1.68]; non-ART: 1.29 [1.25-1.34]). Infants born after fertility treatments had increased risk of admission to neonatal intensive care unit (ART: 1.98 [1.84-2.13]; non-ART: 1.59 [1.51-1.67]) and prolonged birth admission (≥ 3 days) (ART: 1.60 [1.54-1.65]; non-ART: 1.42 [1.39-1.45]). The rate of emergency and in-hospital health services use within the first year was significantly increased for both exposure groups and remained elevated when limiting analyses to term singletons. CONCLUSION(S): Fertility treatments were associated with increased risks of adverse outcomes; however, the overall magnitude of risks was lower for infants conceived via non-ART treatments.
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Nacimiento Prematuro , Embarazo , Lactante , Femenino , Recién Nacido , Humanos , Niño , Nacimiento Prematuro/epidemiología , Recien Nacido Prematuro , Resultado del Embarazo/epidemiología , Recién Nacido de Bajo Peso , Embarazo Múltiple , Ontario/epidemiología , Estudios Retrospectivos , Técnicas Reproductivas Asistidas , HospitalizaciónRESUMEN
OBJECTIVE: Haematogenous dissemination is a prevalent route of colorectal cancer (CRC) metastasis. However, as the gatekeeper of vessels, the role of tumour pericytes (TPCs) in haematogenous metastasis remains largely unknown. Here, we aimed to investigate the heterogeneity of TPCs and their effects on CRC metastasis. DESIGN: TPCs were isolated from patients with CRC with or without liver metastases and analysed by single-cell RNA sequencing (scRNA-seq). Clinical CRC specimens were collected to analyse the association between the molecular profiling of TPCs and CRC metastasis. RNA-sequencing, chromatin immunoprecipitation-sequencing and bisulfite-sequencing were performed to investigate the TCF21-regulated genes and mechanisms underlying integrin α5 on TCF21 DNA hypermethylation. Pericyte-conditional Tcf21-knockout mice were constructed to investigate the effects of TCF21 in TPCs on CRC metastasis. Masson staining, atomic force microscopy, second-harmonic generation and two-photon fluorescence microscopy were employed to observe perivascular extracellular matrix (ECM) remodelling. RESULTS: Thirteen TPC subpopulations were identified by scRNA-seq. A novel subset of TCF21high TPCs, termed 'matrix-pericytes', was associated with liver metastasis in patients with CRC. TCF21 in TPCs increased perivascular ECM stiffness, collagen rearrangement and basement membrane degradation, establishing a perivascular metastatic microenvironment to instigate colorectal cancer liver metastasis (CRCLM). Tcf21 depletion in TPCs mitigated perivascular ECM remodelling and CRCLM, whereas the coinjection of TCF21high TPCs and CRC cells markedly promoted CRCLM. Mechanistically, loss of integrin α5 inhibited the FAK/PI3K/AKT/DNMT1 axis to impair TCF21 DNA hypermethylation in TCF21high TPCs. CONCLUSION: This study uncovers a previously unidentified role of TPCs in haematogenous metastasis and provides a potential diagnostic marker and therapeutic target for CRC metastasis.
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Neoplasias Colorrectales , Neoplasias Hepáticas , Animales , Ratones , Línea Celular Tumoral , Neoplasias Colorrectales/patología , ADN , Regulación Neoplásica de la Expresión Génica , Integrina alfa5/genética , Integrina alfa5/metabolismo , Neoplasias Hepáticas/patología , Metástasis de la Neoplasia , Pericitos/metabolismo , Pericitos/patología , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Microambiente TumoralAsunto(s)
Neoplasias Colorrectales , Neoplasias Hepáticas , Humanos , Células Estrelladas Hepáticas/patología , Endopeptidasas , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patologíaRESUMEN
Objective @#To investigate the occupational exposure to blood-borne pathogens among medical workers in a tertiary general hospital in Hangzhou City from 2010 to 2022, so as to provide the evidence for improving occupational protective measures among medical workers.@*Methods@#The registration and follow-up data of occupational exposure to blood-borne pathogens among medical workers from 2010 to 2022 were collected from the blood-borne occupational exposure monitoring system in a tertiary general hospital in Hangzhou City. The population distribution, occurrence, protection and disposal of occupational exposure to blood-borne pathogens were analyzed using a descriptive epidemiological method.@*Results@#A total of 1 230 cases were reported with occupational exposure to blood-borne pathogens among medical workers in the study hospital from 2010 to 2022, with the highest incidence in 2021 (4.67%) and the lowest incidence in 2010 (0.99%). The incidence of occupational exposure to blood-borne pathogens appeared a tendency forwards a rise from 2010 to 2022 (P<0.05). Of all cases with occupational exposure to blood-borne pathogens, there were 934 women (75.93%), 656 nurses (53.33%), and 514 cases with working experiences of one year and shorter (41.79%). Hand was the predominant site of occupational exposure to blood-borne pathogens (92.03%) and ward was the predominant place of exposure (35.37%), while scalp needle was the predominant mode of exposure (32.68%), and removal of needle was the predominant procedure of exposure (32.36%). A total of 1 106 cases were tested for the blood-borne pathogens in the exposure sources, and 448 cases were tested positive for blood-borne pathogens, with a detection rate of 40.51%. Hepatitis B virus, treponema pallidum and human immunodeficiency virus were the three most common blood-borne pathogens, and there were 739 cases (60.08%) with personal protective equipment during exposure. Following the follow-up surveillance for more than 6 months post-exposure, no infections occurred. @*Conclusions@#Junior nurses and hand exposure were predominant among medical workers with occupational exposure to blood-borne pathogens in the study hospital from 2010 to 2022, and hepatitis B virus was the predominant blood-borne pathogen. No post-exposure infections occurred.
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Traumatic subarachnoid hemorrhage (tSAH) is a critical condition that requires comprehensive management to optimize patient outcomes. Nursing care plays a key role in the overall management of patients with tSAH via various aspects of care, including neurological assessment, monitoring, intervention, and education. In this review, we aim to evaluate the significant contributions of nursing care in managing patients with tSAH. Nurses perform initial neurological assessments, including the glasgow coma scale, pupil reactivity, vital signs, and sensory-motor evaluations. These assessments provide valuable information for early identification of deteriorating neurological status and prompt intervention. Additionally, nurses closely monitor intracranial pressure (ICP), cerebral perfusion pressure, and other hemodynamic parameters, assisting in the prevention and timely detection of secondary brain injury. For example, some strategies to manage ICP include elevating the head of the bed, maintaining adequate oxygenation and ventilation, administering proper medications, and ensuring fluid and electrolyte balance. Also, through careful monitoring, early recognition, and appropriate preventive measures, nursing care could prevent complications, including infections, deep vein thrombosis, and pressure ulcers. Furthermore, nursing care extends beyond physical management and encompasses psychosocial support for patients and their families. Nurses establish therapeutic relationships, providing emotional support, education, and counseling to alleviate anxiety, address concerns, and facilitate coping mechanisms. Education regarding medication management, lifestyle modifications, and the importance of regular follow-up enhances patient compliance and promotes long-term recovery.
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BACKGROUND: The risk of congenital heart disease (CHD) has been found to vary by maternal socioeconomic status (SES) and rural-urban residence. In this study, we examined associations of CHD with two maternal SES indicators and stratified the analysis by maternal rural-urban residence. METHODS: This was a population-based retrospective cohort study. We included all singleton stillbirths and live hospital births from April 1, 2012 to March 31, 2018 in Ontario, Canada. We linked the BORN Information System and Canadian Institute for Health Information databases. Multivariable logistic regression models were used to examine associations of CHD with material deprivation index (MDI), social deprivation index (SDI), and maternal residence while adjusting for maternal age at birth, assisted reproductive technology, obesity, pre-pregnancy maternal health conditions, mental health illness before and during pregnancy, substance use during pregnancy, and infant's sex. MDI and SDI were estimated at a dissemination area level in Ontario and were categorized into quintiles (Q1-Q5). RESULTS: This cohort study included 798,173 singletons. In maternal urban residence, the p trend (Cochran-Armitage test) was less than 0.0001 for both MDI and SDI; while for rural residence, it was 0.002 and 0.98, respectively. Infants living in the most materially deprived neighbourhoods (MDI Q5) had higher odds of CHD (aOR: 1.21, 95% CI: 1.12-1.29) compared to Q1. Similarly, infants living in the most socially deprived neighbourhoods (SDI Q5) had an 18% increase in the odds of CHD (aOR: 1.18, 95% CI: 1.1-1.26) compared to Q1. Rural infants had a 13% increase in the odds of CHD compared to their urban counterparts. After stratifying by maternal rural-urban residence, we still detected higher odds of CHD with two indices in urban residence but only MDI in rural residence. CONCLUSION: Higher material and social deprivation and rural residence were associated with higher odds of CHD. Health interventions and policies should reinforce the need for optimal care for all families, particularly underprivileged families in both rural and urban regions. Future studies should further investigate the effect of social deprivation on the risk of CHD development.
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Cardiopatías Congénitas , Población Rural , Estudios de Cohortes , Femenino , Cardiopatías Congénitas/epidemiología , Cardiopatías Congénitas/etiología , Humanos , Lactante , Recién Nacido , Ontario/epidemiología , Embarazo , Características de la Residencia , Estudios Retrospectivos , Factores Socioeconómicos , Población UrbanaRESUMEN
Vessel co-option has been demonstrated to mediate colorectal cancer liver metastasis (CRCLM) resistance to antiangiogenic therapy. The current mechanisms underlying vessel co-option have mainly focused on "hijacker" tumor cells, whereas the function of the "hijackee" sinusoidal blood vessels has not been explored. Here, we found that the occurrence of vessel co-option in bevacizumab-resistant CRCLM xenografts was associated with increased expression of fibroblast activation protein α (FAPα) in the co-opted hepatic stellate cells (HSCs), which was dramatically attenuated in HSC-specific conditional Fap-knockout mice bearing CRCLM allografts. Mechanistically, bevacizumab treatment induced hypoxia to upregulate the expression of fibroblast growth factor-binding protein 1 (FGFBP1) in tumor cells. Gain- or loss-of-function experiments revealed that the bevacizumab-resistant tumor cell-derived FGFBP1 induced FAPα expression by enhancing the paracrine FGF2/FGFR1/ERK1/-2/EGR1 signaling pathway in HSCs. FAPα promoted CXCL5 secretion in HSCs, which activated CXCR2 to promote the epithelial-mesenchymal transition of tumor cells and the recruitment of myeloid-derived suppressor cells. These findings were further validated in tumor tissues derived from patients with CRCLM. Targeting FAPα+ HSCs effectively disrupted the co-opted sinusoidal blood vessels and overcame bevacizumab resistance. Our study highlights the role of FAPα+ HSCs in vessel co-option and provides an effective strategy to overcome the vessel co-option-mediated bevacizumab resistance.
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Neoplasias Colorrectales , Neoplasias Hepáticas , Inhibidores de la Angiogénesis , Animales , Bevacizumab/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Endopeptidasas , Factor 2 de Crecimiento de Fibroblastos/genética , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Células Estrelladas Hepáticas/patología , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Proteínas de la Membrana , RatonesRESUMEN
INTRODUCTION: Racial differences in adverse maternal and birth outcomes have been studied in other countries, however, there are few studies specific to the Canadian population. In this study, we sought to examine the inequities in adverse perinatal outcomes between Black and White pregnant people in Ontario, Canada. METHODS: We conducted a population-based retrospective cohort study that included all Black and White pregnant people who attended prenatal screening and had a singleton birth in any Ontario hospital (April 1st, 2012-March 31st, 2019). Poisson regression with robust error variance models were used to estimate the adjusted relative risks of adverse perinatal outcomes for Black people compared with White people while adjusting for covariates. RESULTS: Among 412,120 eligible pregnant people, 10.1% were Black people and 89.9% were White people. Black people were at an increased risk of gestational diabetes mellitus, preeclampsia, placental abruption, preterm birth (<37, <34, <32 weeks), spontaneous preterm birth, all caesarean sections, emergency caesarean section, low birth weight (<2500g, <1500g), small-for-gestational-age (<10th percentile, <3rd percentile) neonates, 5-minute Apgar score <4 and <7, neonatal intensive care unit admission, and hyperbilirubinemia requiring treatment but had lower risks of elective caesarean section, assisted vaginal delivery, episiotomy, 3rd and 4th degree perineal tears, macrosomia, large-for-gestational-age neonates, and arterial cord pH≤7.1, as compared with White people. No difference in risks of gestational hypertension and placenta previa were observed between Black and White people. CONCLUSION: There are differences in several adverse perinatal outcomes between Black and White people within the Ontario health care system. Findings might have potential clinical and health policy implications, although more studies are needed to further understand the mechanisms.
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Nacimiento Prematuro , Cesárea , Estudios de Cohortes , Femenino , Humanos , Recién Nacido , Ontario/epidemiología , Placenta , Embarazo , Nacimiento Prematuro/epidemiología , Estudios RetrospectivosRESUMEN
OBJECTIVE: To investigate the interrelationships between maternal socioeconomic status (SES), race and congenital heart diseases (CHD) among infants. DESIGN: Retrospective cohort study. STUDY SETTING: Ontario, Canada. STUDY POPULATION: All singleton stillbirths and live births born in hospitals between 1 April 2012 and 31 March 2018 in Ontario, Canada (n=804 292). OUTCOME: CHD. ANALYSIS: Multivariable logistic regression models were performed to assess associations between maternal neighbourhood household income, education level, race and CHD while adjusting for maternal age at birth, assisted reproductive technology, obesity, pre-existing health conditions, substance use during pregnancy, maternal rural residence and infant's sex. RESULTS: Compared with infants whose mothers lived in the highest median household income neighbourhoods, infants whose mothers lived in the lowest median income neighbourhoods had a higher likelihood of having CHD (adjusted OR 1.15, 95% CI 1.06 to 1.24). Compared with infants whose mothers lived in neighbourhoods with more people with a university or higher degree, those infants whose mothers lived in neighbourhoods with less people with a university or higher degree had a higher chance of developing CHD (adjusted OR 1.26, 95% CI 1.16 to 1.36). Compared with white mothers, black mothers had a higher odds of giving birth to a child with CHD (adjusted OR 1.40, 95% CI 1.27 to 1.54). No association was detected between White and Asian mothers and CHD among infants. CONCLUSIONS: Our study indicates that there are inequities in CHD burden by maternal SES and race in Ontario, Canada. Further investigation is needed to examine racial variation in CHD using more detailed ethnic data.
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Cardiopatías Congénitas , Clase Social , Estudios de Cohortes , Femenino , Cardiopatías Congénitas/epidemiología , Humanos , Lactante , Recién Nacido , Madres , Ontario/epidemiología , Embarazo , Estudios RetrospectivosRESUMEN
A coastal city is studied in this paper. Based on 42 groundwater sampling points, a Piper diagram, the Shukarev classification, the Pearson correlation analysis, Gibbs plots and the ion proportional coefficient method are used to analyze the chemical characteristics and material source. The results show that the groundwater quality in the study area varies greatly from north to south. In the northern inland area (AREA I), the main anions and cations are [Formula: see text] and Ca2+, and the hydrochemical characteristics are mainly HCO3 - Ca, HCO3 â SO4 - Ca and HCO3 - Mg. The ion concentration distribution is uniform, and the groundwater quality is good. By using Gibbs plots and the ion proportional coefficient method, the main source of ions is the dissolution of potassium feldspar, albite and carbonate rock. In contrast, in the southern coastal area (AREA II), the main anions and cations are Cl- and Na+, and the hydrochemical characteristics are mainly Cl - Na. The ion concentration distribution presents a strong spatial difference. The closer the groundwater sampling point is to seawater, the worse the overall groundwater quality. Evaporite dissolution, seawater intrusion, cation exchange effects and human activities are the main factors affecting the groundwater quality in this area. In conclusion, the groundwater quality in northern inland area (AREA I) is better, mainly controlled by the dissolution of rocks. The groundwater quality in southern coastal area (AREA II) changes greatly, mainly controlled by seawater.
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Agua Subterránea , Ciudades , Monitoreo del Ambiente , Contaminantes Químicos del Agua/análisis , Calidad del AguaRESUMEN
Background: An organ donation coordinator plays an important role in the process of organ donation and transplant. Therefore, investigating and analyzing the current situation in organ donation and examining the correlation between professional identity and psychological resilience of human organ donation coordinator, provides a reference for promoting stable development of organ donation. Methods: A total of 48 coordinators of organ donation in Zhejiang Province were recruited for the study by using the method of convenience sampling. The psychological resilience scale and professional identity questionnaire were used to collect data. Results: The results revealed that the total average score of the professional identity of organ donation coordinators was 34.92 ± 8.57. Compared with the median professional identity score of 34.50, the professional identity of the coordinator in this survey was at a moderate level. The total average score of psychological resilience was 64.44 ± 11.91. There was a significant positive correlation between the professional identity of the coordinator and the total score of psychological resilience (r = 0.641, P < 0.01). Conclusion: The professional identity and psychological resilience of the coordinators in Zhejiang Province were found to be in the middle level and the higher the psychological resilience score, the stronger the professional identity of the coordinators. It is important to improve the level of psychological resilience among organ donation coordinators to enhance their professional identity.
Asunto(s)
Trasplante de Órganos , Resiliencia Psicológica , Obtención de Tejidos y Órganos , China , Humanos , Encuestas y CuestionariosRESUMEN
BACKGROUND: This study aimed to examine the relationships between various maternal socioeconomic status (SES) indicators and the risk of congenital heart disease (CHD). METHODS: This was a population-based retrospective cohort study, including all singleton stillbirths and live births in Ontario hospitals from April 1, 2012 to March 31, 2018. Multivariable logistic regression models were performed to examine the relationships between maternal neighbourhood household income, poverty, education level, employment and unemployment status, immigration and minority status, and population density and the risk of CHD. All SES variables were estimated at a dissemination area level and categorized into quintiles. Adjustments were made for maternal age at birth, assisted reproductive technology, obesity, pre-existing maternal health conditions, substance use during pregnancy, rural or urban residence, and infant's sex. RESULTS: Of 804,292 singletons, 9731 (1.21%) infants with CHD were identified. Compared to infants whose mothers lived in the highest income neighbourhoods, infants whose mothers lived in the lowest income neighbourhoods had higher likelihood of developing CHD (adjusted OR: 1.29, 95% CI: 1.20-1.38). Compared to infants whose mothers lived in the neighbourhoods with the highest percentage of people with a university or higher degree, infants whose mothers lived in the neighbourhoods with the lowest percentage of people with university or higher degree had higher chance of CHD (adjusted OR: 1.34, 95% CI: 1.24-1.44). Compared to infants whose mothers lived in the neighbourhoods with the highest employment rate, the odds of infants whose mothers resided in areas with the lowest employment having CHD was 18% higher (adjusted OR: 1.18, 95% CI: 1.10-1.26). Compared to infants whose mothers lived in the neighbourhoods with the lowest proportion of immigrants or minorities, infants whose mothers resided in areas with the highest proportions of immigrants or minorities had 18% lower odds (adjusted OR: 0.82, 95% CI: 0.77-0.88) and 16% lower odds (adjusted OR: 0.84, 95% CI: 0.78-0.91) of CHD, respectively. CONCLUSION: Lower maternal neighbourhood household income, poverty, lower educational level and unemployment status had positive associations with CHD, highlighting a significant social inequity in Ontario. The findings of lower CHD risk in immigrant and minority neighbourhoods require further investigation.