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1.
Zhongguo Zhong Yao Za Zhi ; 46(2): 488-493, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33645138

RESUMO

On the basis of literatures and standards relating to Tibetan medicine, the varieties, origin, standards and efficacy of Saxifragaceae plant used in Tibetan medicine were summarized. According to the findings, 75 species(including varieties) in 8 genera of Saxifragaceae plants, involving 21 varieties, are used in Tibetan medicine. Among them, 9 commonly used varieties, namely Songdi, Sedi, Yajima, Aoledansaierbao, Jiansidawu, Saiguo, Katuer, Sangdi, Maoqinghong, are recorded in Chinese Pharmacopoeia, Ministry Standards for Tibetan Medicine, Tibetan Medicine Standards and other local standards, accounting for 42.9% of the total number of varieties. Tibetan names, Tibetan translation of Chinese names, as well as original plant of Tibetan medicine varieties are quite different in relevant Tibetan medicine standards and literatures, which resulted in common phenomena of synonym and homonym. The standards of most varieties only involve characters, and microscopic, physical and chemical identification, with low quality standards. Based on the results of the analysis, this paper suggests strengthening surveys on herbal textual research, resources and current utilization of Saxifragaceae plants used in Tibetan medicine, summarizing the varieties, establishing improved quality standards, and perfor-ming a comparative study on therapeutic material basis and biological activity of different original plants, in order to promote rational use of these medicinal plant resources, and ensuring the accuracy, safety, and effectiveness of clinical medication.


Assuntos
Medicamentos de Ervas Chinesas , Plantas Medicinais , Saxifragaceae , Grupo com Ancestrais do Continente Asiático , Humanos , Medicina Tradicional Tibetana , Padrões de Referência
2.
Artigo em Inglês | MEDLINE | ID: mdl-33569584

RESUMO

With the rapid application of nuclear technology, radiation protection is becoming more and more important. For external radiation protection, most of the national metrology institutes in the world have established the primary standard of X-ray air kerma in (10-250) kV and Cs-137 gamma ray, but the energy between 250 and 662 keV needs the establishment of traceability. To provide solution to such issue, a graphite cavity ionization chamber was constructed at National Institute of Metrology to measure the air kerma in (250-450) kV X-ray. The relative standard uncertainty of the method is 0.45%. Two different types of ionization chambers were used to measure the air kerma of N-300 radiation quality, and the result has a deviation of 0.09%.

3.
Biomed Res Int ; 2021: 8828299, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33623789

RESUMO

Circular RNAs are a class of RNAs with a covalently closed configuration, and several members of them have been reported to be capable of regulating various biological processes and predicting the outcome of disease. Among them, circular RNA circ-ITCH has been identified to be aberrantly expressed and associated with disease progression in diverse cancers. However, the correlation of circ-ITCH expression with clinicopathological features, as well as the prognosis of cancers, remains inconclusive. Therefore, a meta-analysis was performed to investigate the clinical significance of circ-ITCH in cancers by systematically summarizing all eligible literatures. Up to August 31, 2020, relevant articles were searched in PubMed, Web of Science, Cochrane library, Embase, CNKI, and Wanfang databases. Pooled hazard ratios (HRs) and odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. A total of 1604 patients from 14 studies were included in this meta-analysis. The results showed that cancer patients with low circ-ITCH expression were more susceptible to develop lymph node metastasis (OR = 2.25, 95% CI: 1.67-3.02, p ≤ 0.01), larger tumor size (OR = 3.01, 95% CI: 2.01-4.52, p ≤ 0.01), advanced TNM stage (OR = 2.82, 95% CI: 1.92-4.14, p ≤ 0.01), and poor overall survival (OS) (HR = 2.45, 95% CI: 2.07-2.90, p ≤ 0.01, univariate analysis; HR = 2.69, 95% CI: 1.82-3.96, p ≤ 0.01, multivariate analysis). Thus, low circ-ITCH expression was significantly associated with aggressive clinicopathological features and unfavorable outcome in various cancers. Therefore, circ-ITCH may serve as a molecular therapy target and a prognostic marker in human cancers.

4.
Org Biomol Chem ; 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33624667

RESUMO

Two new diterpene derivatives were obtained by semisynthesis from enzymatically generated catenul-14-en-6-ol. The EI-MS fragmentation mechanisms of three enzyme products and the two semisynthetic derivatives were investigated by extensive 13C-labelling experiments.

5.
Spectrochim Acta A Mol Biomol Spectrosc ; 252: 119490, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33524815

RESUMO

The objective of this study was to establish a novel method for the determination of N-methylaniline (NMA) based on azo coupling reaction in infant pacifiers prepared with food contact silicone materials by combining thin layer chromatography (TLC) with surface-enhanced resonance Raman scattering (SERRS). TLC was used to separate the azo reaction products to confirm the component spot of azo compound, then the spot of azo compound mixed with silver sol on the TLC plate was qualitatively detected by SERRS. The limit of detection (LOD) of the method is as low as 0.50 ppm for NMA. The influence of sample matrix about the TLC-SERRS detection of NMA was investigated by experiment of simulated positive sample, and the NMA in infant pacifiers exposed to silica gel products was detected. The method of TLC-SERRS for the determination of NMA in infant pacifiers prepared with food contact silicone materials was established, and the real samples were detected. Compared with the methods ever reported, the method has the advantages of high sensitivity, specificity and low cost. It provides a new reference method for establishing a safety system for food contact silicone materials.

6.
Mech Ageing Dev ; 195: 111442, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33539906

RESUMO

Doxorubicin (Dox)-induced cardiotoxicity could lead to dilated cardiomyopathy and heart failure. Our previous study reported the protective effects of Klotho against hyperglycemia-induced cardiomyopathy. We investigated whether Klotho alleviated Dox-induced cardiotoxicity. Neonatal rat ventricular cardiomyocytes and H9c2 cells were incubated with 5 µM Dox for 24 h with or without Klotho (0.1 µg/mL). Dox-induced cardiotoxicity model was approached in C57BL/6 mice. Cardiac function and serum enzyme activity, apoptosis and mitochondrial dysfunction were measured. We found that pretreatment with Klotho significantly reduced Dox-induced apoptosis in cardiomyocytes. In Dox-treated mice, Klotho also suppressed cardiac cell death and improved cardiac function. Moreover, the expression of Dynamin-related protein 1 (Drp1) was increased after Dox-treatment both in vitro and in vivo, which was related to apoptosis in cardiomyocytes. In vitro experiments, Drp1 ser 616 phosphorylation post-Dox stimulation could be significantly attenuated by Klotho or Drp1 specific inhibitor Mdivi-1. Overexpression of Drp1 in cardiomyocytes increased Dox-induced heart injury which could also be attenuated by Klotho. This study demonstrated that Klotho alleviated Dox-induced cardiotoxicity by reducing apoptosis and mitochondrial fission through down-regulating Drp1 expression. Our findings highlighted new targets for the therapy of Dox-induced cardiomyopathy.

7.
Aging (Albany NY) ; 122021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-33429363

RESUMO

Tumors are complex ecosystems harboring multiple cell types which might play a critical role in tumor progression and treatment response. The endometrial epithelial cell identities and immune microenvironment of endometrial carcinoma (ECC) are poorly characterized. In this study, a cellular map of endometrial carcinoma was generated by profiling 30,780 cells isolated from tumor and paratumor tissues from five patients using single-cell RNA sequencing. 7 cell types in lymphocytes, 7 types in myeloid cells and 3 types in endometrial epithelial cells were identified. Distinct CD8+ T cell states and different monocyte-macrophage populations were discovered, among which exhausted CD8+ T cells and macrophages were preferentially enriched in tumor. Both CD8+ T cells and macrophages comport with continuous activation model. Gene expression patterns examination and gene ontology enrichment analysis of endometrial epithelial cells revealed 3 subtypes: stem-like cells, secretory glandular cells and ciliated cells. Overall, our study presents a view of endometrial carcinoma at single-cell resolution that reveals the characteristics of endometrial epithelial cells in the endometrium, and provides a cellular landscape of the tumor immune microenvironment.

8.
Plant Physiol Biochem ; 160: 175-183, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33497848

RESUMO

Peanut is an important oilseed crop whose production is threatened by various abiotic and biotic stresses. Study of the molecular mechanism of salt tolerance could provide important information for the salt tolerance of this crop. WRKY transcription factors (TFs) are one of the largest TF families in plants and are involved in growth and development, defense regulation and the stress response. Here, we cloned a novel WRKY transcription factor gene belonging to the WRKY IIc subfamily, AhWRKY75, from the salt-tolerant mutant M34. The expression of AhWRKY75 was induced by NaCl stress treatment. After salt treatment, AhWRKY75-overexpressing peanuts grew better than wild-type plants. Furthermore, several genes related to the reactive oxygen species (ROS) scavenging system were up-regulated; the activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) were significantly higher in transgenic lines than in non-transgenic control plants; and the malondialdehyde (MDA) and superoxide anion contents were significantly lower in transgenic lines than in control plants. The net photosynthetic rate (Pn), stomatal conductance (GS) and transpiration rate (Tr) of transgenic lines were significantly higher in transgenic plants than in control plants, and the intercellular CO2 concentration (Ci) was significantly lower in transgenic plants than in control plants. These results demonstrated that the AhWRKY75 gene conferred salt tolerance in transgenic peanut lines by improving the efficiency of the ROS scavenging system and photosynthesis under stress treatment. This study identifies a novel WRKY gene for enhancing the tolerance of peanut and other plants to salt stress.


Assuntos
Arachis , Proteínas de Plantas/fisiologia , Tolerância ao Sal , Fatores de Transcrição/fisiologia , Arachis/genética , Arachis/fisiologia , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/fisiologia , Tolerância ao Sal/genética , Estresse Fisiológico , Fatores de Transcrição/genética
9.
Hypertension ; 77(3): 868-881, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33486984

RESUMO

Genome-wide association studies have identified that NPR-C (natriuretic peptide receptor-C) variants are associated with elevation of blood pressure. However, the mechanism underlying the relationship between NPR-C and blood pressure regulation remains elusive. Here, we investigate whether NPR-C regulates Ang II (angiotensin II)-induced hypertension through sodium transporters activity. Wild-type mice responded to continuous Ang II infusion with an increased renal NPR-C expression. Global NPR-C deficiency attenuated Ang II-induced increased blood pressure both in male and female mice associated with more diuretic and natriuretic responses to a saline challenge. Interestingly, Ang II increased both total and phosphorylation of NCC (NaCl cotransporter) abundance involving in activation of WNK4 (with-no-lysine kinase 4)/SPAK (Ste20-related proline/alanine-rich kinase) which was blunted by NPR-C deletion. NCC inhibitor, hydrochlorothiazide, failed to induce natriuresis in NPR-C knockout mice. Moreover, low-salt and high-salt diets-induced changes of total and phosphorylation of NCC expression were normalized by NPR-C deletion. Importantly, tubule-specific deletion of NPR-C also attenuated Ang II-induced elevated blood pressure, total and phosphorylation of NCC expression. Mechanistically, in distal convoluted tubule cells, Ang II dose and time-dependently upregulated WNK4/SPAK/NCC kinase pathway and NPR-C/Gi/PLC/PKC signaling pathway mediated NCC activation. These results demonstrate that NPR-C signaling regulates NCC function contributing to sodium retention-mediated elevated blood pressure, which suggests that NPR-C is a promising candidate for the treatment of sodium retention-related hypertension.

10.
J Org Chem ; 86(4): 3367-3376, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33497233

RESUMO

The chemical investigation of the South China Sea soft coral Sinularia humilis has resulted in the isolation of a library of diverse diterpenoids, including four new cembranoids, namely, humilisins A-D (1-4), two new uncommon diterpenoids possessing a tetradecahydrocyclopenta[3',4']cyclobuta[1',2':4,5]cyclonona[1,2-b]oxirene ring system, namely, humilisins E and F (5 and 6), and eight known related compounds (7-14). Humilisin A (1) is the first cembranoid with an ether linkage between C-3 and C-7. The structures and absolute configurations of 1-8 were determined by extensive spectroscopic data analyses, chemical reactions, and a series of quantum chemical calculations including quantum mechanical-nuclear magnetic resonance (QM-NMR), time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD), and optical rotatory dispersion (ORD) methods. In bioassay, compound 6 displayed anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated BV-2 microglia cells.

11.
Mediators Inflamm ; 2021: 6699499, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33510583

RESUMO

Method: Mice were randomly assigned to the sham, I/R, Oxy, and I/R with Oxy groups. Oxy was injected intraperitoneally 30 min before tourniquet placement. Morphological changes of the gastrocnemius muscle in these mice were assessed by hematoxylin-eosin (HE) staining and electron microscopy. Expression levels of TLR4, NF-κB, SIRT1, and PGC-1α in the skeletal muscles were detected by western blot. Blood TNF-α levels, gastrocnemius muscle contractile force, and ATP concentration were examined. Results: Compared with the I/R group, Oxy pretreatment attenuated skeletal muscle damage, decreased serum TNF-α levels, and inhibited the expression levels of TLR4/NF-κB in the gastrocnemius muscle. Furthermore, Oxy treatment significantly increased serum ATP levels and the contractility of the skeletal muscles. SIRT1 and PGC-1α levels were significantly reduced in gastrocnemius muscle after I/R. Oxy pretreatment recovered these protein expression levels. Conclusion: Tourniquet-induced acute limb I/R results in morphological and functional impairment in skeletal muscle. Pretreatment with Oxy attenuates skeletal muscle from acute I/R injury through inhibition of TLR4/NF-κB-dependent inflammatory response and protects SIRT1/PGC-1α-dependent mitochondrial function.

12.
Eur J Pain ; 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33497529

RESUMO

BACKGROUND: Relationships between iron dependent ferroptosis and nerve system diseases have been recently revealed. However, the role of ferroptosis in neuropathic pain (NeP) remains to be elucidated. Thus, we aimed to investigate whether ferroptosis in spinal cord contributes to NeP induced by a chronic constriction injury (CCI) of the sciatic nerve. METHOD: Forty Sprague Dawley rats received CCI or sham surgery, and were randomly assigned to the following four groups: sham group; CCI+LIP group; CCI+Veh group; and CCI group. Liproxstatin-1 or corn oil were separately injected intraperitoneally for three consecutive days after surgery in the CCI+LIP or CCI+Veh group. The mechanical and thermal hypersensitivities were tested after surgery. Biochemical and morphological changes related to ferroptosis in the spinal cord were also assessed. These included iron content, glutathione peroxidase 4 (GPX4) and anti-acyl-CoA synthetase long-chain family member 4 (ACSL4) expression, lipid peroxidation assays, as well as mitochondrial morphology. RESULT: CCI-induced NeP was followed by iron accumulation, increased lipid peroxidation, and dysregulation of ACSL4 and GPX4. Moreover, transmission electron microscopy confirmed the presence of aberrant morphological changes on mitochondrial, such as mitochondria shrinkage and membrane rupture. Furthermore, the administration of liproxstatin-1 on CCI rats attenuated hypersensitivities, lowered the iron level, decreased spinal lipid peroxidation, restored the dysregulations in GPX4 and ACSL4 levels, and protected against CCI induced morphological changes in mitochondria. CONCLUSION: Our findings indicated the involvement of ferroptosis in CCI induced NeP, and point to ferroptosis inhibitors such as liproxstatin-1 as potential therapies for hypersensitivity induced by peripheral nerve injury.

13.
Parasite Immunol ; : e12822, 2021 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-33454990

RESUMO

BACKGROUND: More than 11 million people were estimated to have been infected by Schistosoma japonicum in China before the 1950s. However, few studies have been conducted to evaluate the longitudinal effects of previous schistosome infection (PSI). OBJECTIVE: We aimed to evaluate the association of PSI with fatty liver and coronary heart disease in China. METHODS: A cross-sectional study was conducted in regions which were all reportedly heavily endemic for S japonicum in China. All data were collected using a questionnaire administered and health examinations by well-trained medical professionals. 2867 participants aged 40 years and older were enrolled. Among these, 731 patients with PSI were selected as study subjects and 2136 subjects served as controls. Comparisons between groups were performed with or without an adjustment for a covariate, using Student's t tests for continuous variables and chi-square testing for categorical variables. Multivariable logistic models were used to estimate the associations between PSI and fatty liver or coronary heart disease. RESULTS: The PSI participants had significantly lower levels of triglyceride, low-density lipoprotein cholesterol, fasting blood glucose, uric acid, serum creatinine, urea nitrogen, platelet, total protein and globulin as well as a lower prevalence of fatty liver (13.3% vs 53.6%, P < .001) and coronary heart disease (3.4% vs 6.0%, P < .05) compared with the uninfected, contemporaneous controls (without PSI), whereas the PSI participants had higher levels of high-density lipoprotein cholesterol, direct bilirubin and a higher prevalence of hepatic dysfunction compared with those without PSI (P < .05). CONCLUSION: We found PSI significantly negatively associated with fatty liver and coronary heart disease. However, further studies on schistosomiasis may provide new directions for prevention and treatment of fatty liver and coronary heart disease.

14.
J Org Chem ; 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33290070

RESUMO

A novel diterpenoid, sinueretone A (1), featuring an unprecedented tricyclo[12.1.0.05,9]pentadecane carbon framework, along with two new (2 and 3) and one known (4) casbane diterpenoids were isolated from the South China Sea soft coral Sinularia erecta. The structures of the new compounds, especially their absolute stereochemistry, were established by extensive spectroscopic analysis, various quantum chemical calculations, and/or X-ray diffraction analyses. A plausible biogenetic relationship of 1-4 was proposed, which gave an insight for future biomimetic synthesis of the novel compounds. In a bioassay, compounds 1 and 2 displayed interesting anti-inflammatory activity by the inhibition of lipopolysaccharide-induced tumor necrosis factor-α protein release.

15.
J Hazard Mater ; 405: 124642, 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33301972

RESUMO

Total removal of organic mercury in industrial wastewater is a crucially important task facing environmental pollution in the current world. Herein, we demonstrate the fabrication of Au-NiFe layered double hydroxide (LDH)/rGO nanocomposite as not only an efficient nanozyme with oxidase-like activity but also an efficient surface-enhanced Raman spectroscopy (SERS) substrate to determine organic mercury, with the minimum detection concentration as low as 1 × 10-8 M. According to the binding energy of X-Ray photoelectron spectrometer (XPS) and the free radicals of electron paramagnetic resonance (EPR) spectra, the mechanism of catalytic enhanced degradation is the production of Au-amalgam on Au surface, accelerating the electron transfer and the generation of O2•- radicals from oxygen molecules and •CH3 radicals from the methyl group in MeHg to participate the oxidase-like reaction. Furthermore, the Au-NiFe LDH/rGO nanocomposite is able to degrade and remove 99.9% of organic mercury in two hours without the secondary pollution by Hg2+. In addition, the material can be used for the multiple degradation-regeneration cycles in actual applications, which is significant in terms of the environmental and economic point of view. This work may open a new horizon for both highly sensitive detection and thorough degradation of organic mercury in environmental science and technology.

16.
J Mech Behav Biomed Mater ; 114: 104207, 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33307420

RESUMO

Here we characterize and compare the anisotropic and nonlinear viscoelastic properties of the posterior eye of advanced dry age-related macular degeneration (AMD) patients and age-matched normal subjects. Ten normal horizontal, ten normal vertical, ten AMD horizontal, and ten AMD vertical strips of the macular retina and the underlying choroid and sclera were preloaded, preconditioned, and subjected to incremental stress-relaxation tests in body-temperature saline. The stress-relaxation response was characterized by a fully nonlinear viscoelastic formulation in which the relaxation modulus was approximated by a Prony series and a second-order polynomial using the comprehensive viscoelastic characterization method. Normal retina, choroid, and sclera were found to be anisotropic, whereas AMD tissues were isotropic. AMD retina and choroid showed greater stress-relaxation response than normal tissues (p < 0.05), whereas AMD sclera had smaller stress-relaxation response than normal tissue (p < 0.05). The nonlinear viscoelastic stress-strain relationship of the posterior eye is hence describable for the first time.

17.
Nat Prod Res ; : 1-7, 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33356576

RESUMO

A new diterpenoid with an unusual capnosane skeleton, sinuhumilol A (1), alone with twelve known diverse compounds (2-13), were isolated from the South China Sea soft coral Sinularia humilis. Their structures and stereochemistry were elucidated by extensive spectroscopic analysis, quantum chemical calculations, and/or by the comparison of the spectroscopic data with those reported in the literature. In bioassay, compound 11 exhibited interesting specific cytotoxicity against the human colon adenocarcinoma cell line HT-29 with IC50 value of 12.5 µM.

18.
Chin J Nat Med ; 18(11): 839-843, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33308605

RESUMO

Lobane-type diterpenoids are not frequently discovered from marine soft corals. In this paper, three new lobane type diterpenes, 13-methoxyloba-8,10,15(16),17(18)-tetraene (1), 8,10,13(15)Z,16E-lobatetraene (2) and 19-hydroxy-lobatetraene (3), and a new natural compound, 17,18-epoxyloba-16-acetoxy-8,10,13(15)-trien (4), co-occurring with a known related diterpenoid, 18-methoxyloba-8,10,13(15),16(17)-tetraene (5), were isolated from the South China Sea soft coral Sinularia polydactyla. The structures of new compounds were determined by extensive spectroscopic analysis and by comparison with those reported in the literature. In bioassay, all the isolates were inactive on antibacterial, PTP1B inhibitory, and immunological activities. This study increased the chemical diversity of marine diterpenoids.

19.
Dermatology ; : 1-5, 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33326962

RESUMO

OBJECTIVES: Pain and psychological disorders are the 2 most commonly occurring symptom clusters in patients with postherpetic neuralgia (PHN). This study aimed to investigate the risk factors for anxiety and depressive disorders in patients with PHN. METHODS: Retrospectively, we examined the potential risk factors of anxiety and depression among patients with PHN from the clinic medical records of the Third Affiliated Hospital of Sun Yat-Sen University from 2017 to 2019. The Chinese version of the Hospital Anxiety and Depression Scale was used to assess anxiety and depression. Patients were retrospectively allocated to 2 groups - PHN with and without anxiety/depression - and compared to identify the differential patient characteristics. RESULTS: Cases of 661 patients who were diagnosed with PHN were included. Anxiety and depression developed in 69.0% (456/661) and 65.8% (435/661) of the enrolled patients with PHN, respectively. Results of univariate regression analyses showed that female sex, magnitude of pain intensity, time from onset of rash and extent of spread of rashes were significantly associated with anxiety and depression in patients with PHN. Multivariate analysis revealed that both anxiety and depression states significantly correlated with female sex, magnitude of pain intensity, and extent of spread of rashes. CONCLUSIONS: Anxiety and depression were not uncommon in patients with PHN. Women with PHN who experience severe pain and develop extensive rashes have a high risk of developing anxiety and depressive disorders.

20.
Lancet Planet Health ; 4(11): e512-e521, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33159878

RESUMO

BACKGROUND: Various retrospective studies have reported on the increase of mortality risk due to higher diurnal temperature range (DTR). This study projects the effect of DTR on future mortality across 445 communities in 20 countries and regions. METHODS: DTR-related mortality risk was estimated on the basis of the historical daily time-series of mortality and weather factors from Jan 1, 1985, to Dec 31, 2015, with data for 445 communities across 20 countries and regions, from the Multi-Country Multi-City Collaborative Research Network. We obtained daily projected temperature series associated with four climate change scenarios, using the four representative concentration pathways (RCPs) described by the Intergovernmental Panel on Climate Change, from the lowest to the highest emission scenarios (RCP 2.6, RCP 4.5, RCP 6.0, and RCP 8.5). Excess deaths attributable to the DTR during the current (1985-2015) and future (2020-99) periods were projected using daily DTR series under the four scenarios. Future excess deaths were calculated on the basis of assumptions that warmer long-term average temperatures affect or do not affect the DTR-related mortality risk. FINDINGS: The time-series analyses results showed that DTR was associated with excess mortality. Under the unmitigated climate change scenario (RCP 8.5), the future average DTR is projected to increase in most countries and regions (by -0·4 to 1·6°C), particularly in the USA, south-central Europe, Mexico, and South Africa. The excess deaths currently attributable to DTR were estimated to be 0·2-7·4%. Furthermore, the DTR-related mortality risk increased as the long-term average temperature increased; in the linear mixed model with the assumption of an interactive effect with long-term average temperature, we estimated 0·05% additional DTR mortality risk per 1°C increase in average temperature. Based on the interaction with long-term average temperature, the DTR-related excess deaths are projected to increase in all countries or regions by 1·4-10·3% in 2090-99. INTERPRETATION: This study suggests that globally, DTR-related excess mortality might increase under climate change, and this increasing pattern is likely to vary between countries and regions. Considering climatic changes, our findings could contribute to public health interventions aimed at reducing the impact of DTR on human health. FUNDING: Korea Ministry of Environment.

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