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1.
Vaccine ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33199077

RESUMO

BACKGROUND: Community-acquired pneumonia (CAP) is one of the major global health problems worldwide. However, the epidemiological information of CAP is limited in China. This study aimed to estimate the incidence rate of CAP and describe the epidemiologic characteristics among the Chinese population. METHODS: We conducted a retrospective analysis of CAP incidence using the Chinese Urban Basic Medical Insurance database of 23 provinces in 2016, which covered 427.52 million urban beneficiaries of all age groups in Mainland China. CAP episodes were identified using a diagnosis-term-derived algorithm, and multiple CAP records of one single person within 90 continuous days were considered as one single episode. The incidence rates were calculated and described by sex, age, region, and season. RESULTS: A total of 1.42 million patients were identified as having one or more CAP episodes, and finally a sum of 1.48 million CAP episodes were counted. The overall incidence of CAP was 7.13 (95% CI: 6.11-8.15) per 1000 person-years, in males 7.32 (95% CI: 6.28-8.35) and females 6.93 (95% CI: 5.92-7.94) per 1000 person-years, respectively. The incidence varied by age with a U-shaped curve peaking in children aged < 5 years old [65.80 (95% CI: 62.52-69.08)] and elderly population aged ≥ 80 years old [14.98 (95% CI: 13.63-16.34)]. The incidence varied markedly by regions. Furthermore, the rate showed a clear seasonal trend, which peaked in spring, decreased in summer and autumn, and re-ascended in winter. CONCLUSION: This study reveals a relatively high level of CAP incidence in China. These findings provide baseline data for establishing effective prevention strategies, targeted at susceptible populations, regions, and seasons in China.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33205940

RESUMO

The combination of gene therapy with chemotherapeutics provides an efficacious strategy for enhanced tumor therapy. RNA-cleaving DNAzyme has been recognized as a promising gene-silencing tool, while its combination with chemotherapeutic drugs has been limited by the lack of an effective codelivery system to allow sufficient intracellular DNAzyme activation, which requires specific metal ions as a cofactor. Here, a self-activatable DNAzyme/drug core-shell codelivery system is fabricated to combat triple-negative breast cancer (TNBC). The hydrophobic chemotherapeutic, rapamycin (RAP), is self-assembled into the pure drug nanocore, and the metal-organic framework (MOF) shell based on coordination between Mn2+ and tannic acid (TA) is coated on the surface to coload an autophagy-inhibiting DNAzyme. The nanosystem efficiently delivers the payloads into tumor cells, and upon endocytosis, the MOF shell is disintegrated to release the therapeutics in response to an acidic endo/lysosome environment and intracellular glutathione (GSH). Notably, the coreleased Mn2+ serves as the cofactor of DNAzyme for effective self-activation, which suppresses the expression of Beclin 1 protein, the key initiator of autophagy, resulting in a significantly strengthened antitumor effect of RAP. Using tumor-bearing mouse models, the nanosystem could passively accumulate into the tumor tissue, impose potent gene-silencing efficacy, and thus sensitize chemotherapy to inhibit tumor growth upon intravenous administration, providing opportunities for combined gene-drug TNBC therapy.

3.
Hum Vaccin Immunother ; : 1-8, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33054581

RESUMO

Since 2019, three types of HPV vaccine have been approved for use in mainland China. High quality messages are crucial for vaccine acceptance, but little is known about the online information quality concerning HPV vaccine in China. "HPV vaccine" and "cervical cancer vaccine" in the form of Chinese were used as keywords through search engines from personal computer (PC), portable mobile device (PMD), and WeChat Public Accounts in 2019. Readability, information content, as well as DISCERN scores were evaluated for each message included. Characteristics associated with quality indicators of the messages were also analyzed. A total of 294 messages from PC engines (104, 35%), PMD engines (128, 43%) and WeChat (62, 21%) were assessed. Most (269, 91%) messages required at least undergraduate readability level. The most frequently reported theme was HPV vaccine and its function (273, 93%), while the least was information regarding quality, safety and side effects (129, 44%). The frequency of messages with at least one error was 132 (45%). The median of sum DISCERN scores was 42 (IQR = 14), and only one (< 1%) message showed good DISCERN quality. Messages retrieved from PC engines and those with pictures were of better overall quality. The overall quality of HPV vaccine-related online messages in Chinese websites was not optimal. Government and health professionals should promote information quality construction to improve the status of HPV vaccination messages online.

4.
PLoS Med ; 17(8): e1003180, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32760065

RESUMO

BACKGROUND: Hip fracture is a public health concern because of its considerable morbidity, excess mortality, great risk of disability, and high societal healthcare costs. China has the largest population of older people in the world and is experiencing rapid population aging and facing great challenges from an increasing number of hip fractures. However, few studies reported the epidemiology, especially at a national level. We aimed to evaluate trends in hip fracture incidence and associated costs for hospitalization in China. METHODS AND FINDINGS: We conducted a population-based study using data between 2012 and 2016 from the national databases of Urban Employee Basic Medical Insurance and Urban Resident Basic Medical Insurance in China, covering about 480 million residents. Data from around 102.56 million participants aged 55 years and older during the study period were analyzed. A total of 190,560 incident hip fracture patients (mean age 77.05 years, standard deviation 8.94; 63.99% female) were identified. Primary outcomes included the age- and sex-specific incidences of hip fracture. Associated annual costs for hospitalization were also calculated. Incidence was described as per 100,000 person-years at risk, and 95% confidence intervals were computed assuming a Poisson distribution. Hip fracture incidence overall in China did not increase during the study period despite rapid population aging. Incidence per 100,000 was 180.72 (95% CI 137.16, 224.28; P < 0.001) in 2012 and 177.13 (95% CI 139.93, 214.33; P < 0.001) in 2016 for females, and 121.86 (95% CI 97.30, 146.42; P < 0.001) in 2012 and 99.15 (95% CI 81.31, 116.99; P < 0.001) in 2016 for males. For both sexes, declines in hip fracture incidence were observed in patients aged 65 years and older, although incidence was relatively stable in younger patients. However, the total absolute number of hip fractures in those 55 years and older increased about 4-fold. The total costs for hospitalization showed a steep rise from US$60 million to US$380 million over the study period. Costs for hospitalization per patient increased about 1.59-fold, from US$4,300 in 2012 to US$6,840 in 2016. The main limitation of the study was the unavailability of data on imaging information to adjudicate cases of hip fracture. CONCLUSIONS: Our results show that hip fracture incidence among patients aged 55 and over in China reached a plateau between 2012 and 2016. However, the absolute number of hip fractures and associated medical costs for hospitalization increased rapidly because of population aging.


Assuntos
Fraturas do Quadril/diagnóstico , Fraturas do Quadril/epidemiologia , Vigilância da População , População Urbana/tendências , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
5.
Nonlinear Dyn ; : 1-10, 2020 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-32836800

RESUMO

The pandemic of coronavirus disease 2019 (COVID-19) has threatened the social and economic structure all around the world. Generally, COVID-19 has three possible transmission routes, including pre-symptomatic, symptomatic and asymptomatic transmission, among which the last one has brought a severe challenge for the containment of the disease. One core scientific question is to understand the influence of asymptomatic individuals and of the strength of control measures on the evolution of the disease, particularly on a second outbreak of the disease. To explore these issues, we proposed a novel compartmental model that takes the infection of asymptomatic individuals into account. We get the relationship between asymptomatic individuals and critical strength of control measures theoretically. Furthermore, we verify the reliability of our model and the accuracy of the theoretical analysis by using the real confirmed cases of COVID-19 contamination. Our results, showing the importance of the asymptomatic population on the control measures, would provide useful theoretical reference to the policymakers and fuel future studies of COVID-19.

6.
Clin Respir J ; 2020 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-32474995

RESUMO

INTRODUCTION: The long-term mortality rate in adolescent and middle-aged patients with low-medium risk community-acquired pneumonia (CAP) remains unelucidated. OBJECTIVE: Understanding the long-term mortality rate in adolescent and middle-aged patients with low-medium risk CAP in Beijing, China, to provide a basis for the long-term management of CAP patient. METHODS: A follow-up survey was conducted telephonically from December 2017 to January 2018 to assess the survival status among 808 patients from a CAP-China cohort enrolled from 10 general hospitals in Beijing between November 2010 and April 2012. The all-cause mortality rate was determined and Cox's proportional hazard model was performed to identify potential factors predicting mortality. RESULTS: Among the 808 patients, the mean age (SD) was 45.4 (19.6) year-old and the median (IQR) pneumonia severity index (PSI) score was 42.0 (35.8). Survival status for a total of 426 (52.7%) were determined during the follow-up and the non-follow-up patients were with slightly larger PSI score. The mean age (SD) for the follow-up patients were 44.6 (18.7) year-old and the median (IQR) PSI score was 42.0 (33.3). Over a median of 7 years, 32 participants died and the cumulative 1-, 3-, 5- and 7-year all-cause mortality rates were 1.6%, 4.2%, 5.9% and 7.5%, respectively. The average annual standardized mortality rate among the study participants was 9.79%, which was significantly higher than the mortality rate of 5.20‰ among Beijing residents in 2016. Multivariable Cox proportional hazards analyses revealed that age, comorbidity and PSI were independent prognostic factors associated with long-term mortality, with hazard ratios of 4.953 (95% confidence interval [CI]3.270-7.502), 2.393 (95% CI 1.148-4.985) and 3.553 (95% CI 2.607-4.843), respectively. CONCLUSION: The long-term mortality rate is higher among patients with CAP compared with the age-adjusted general population in the same city. Age, comorbidity and initial PSI class are independently prognostic factors for the long-term mortality rate.

7.
BMC Cancer ; 20(1): 499, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32487106

RESUMO

BACKGROUND: To investigate the performance of primary ultrasound (P-US) screening for breast cancer, and that of supplemental ultrasound (S-US) screening for breast cancer after negative mammography (MAM). METHODS: Electronic databases (PubMed, Scopus, Web of Science, and Embase) were systematically searched to identify relevant studies published between January 2003 and May 2018. Only high-quality or fair-quality studies reporting any of the following performance values for P-US or S-US screening were included: sensitivity, specificity, cancer detected rate (CDR), recall rate (RR), biopsy rate (BR), proportion of invasive cancers among screening-detected cancers (ProIC), and proportion of node-negative cancers among screening-detected invasive cancers (ProNNIC). RESULTS: Twenty-three studies were included, including 12 studies in which S-US screening was used after negative MAM and 11 joint screening studies in which both primary MAM (P-MAM) and P-US were used. Meta-analyses revealed that S-US screening could detect 96% [95% confidential intervals (CIs): 82 to 99%] of occult breast cancers missed by MAM and identify 93% (95% CIs: 89 to 96%) of healthy women, with a CDR of 3.0/1000 (95% CIs: 1.8/1000 to 4.6/1000), RR of 8.8% (95% CIs: 5.0 to 13.4%), BR of 3.9% (95% CIs: 2.7 to 5.4%), ProIC of 73.9% (95% CIs: 49.0 to 93.7%), and ProNNIC of 70.9% (95% CIs: 46.0 to 91.6%). Compared with P-MAM screening, P-US screening led to the recall of significantly more women with positive screening results [1.5% (95% CIs:0.6 to 2.3%), P = 0.001] and detected significantly more invasive cancers [16.3% (95% CIs: 10.6 to 22.1%), P < 0.001]. However, there were no significant differences for other performance measures between the two screening methods, including sensitivity, specificity, CDR, BR, and ProNNIC. CONCLUSIONS: Current evidence suggests that S-US screening could detect occult breast cancers missed by MAM. P-US screening has shown to be comparable to P-MAM screening in women with dense breasts in terms of sensitivity, specificity, cancer detection rate, and biopsy rate, but with higher recall rates and higher detection rates for invasive cancers.

8.
NPJ Prim Care Respir Med ; 30(1): 28, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32546685

RESUMO

The study aimed to investigate the demographic characteristics, clinical features, diagnoses, and treatments of hospitalized exacerbation COPD patients, as well as their disease prognoses and economic costs. The study planned to enroll 7600 hospitalized patients (aged ≥18 years with main diagnosis as AECOPD). Study patients were recruited since September 2017, followed up with a 3-year observing period. In the baseline visit, information on demographic characteristics, clinical features, diagnoses, and treatments were collected. In the following visits, treatments and examinations, recurrence of AECOPD, re-admission to hospital, complications, and mortality were recorded. Several validated questionnaires were applied at specific visits. This study included data from 1 September 2017 until 31 December 2022. The data would be used to estimate all-cause mortality during hospital stay, AECOPD recurrence within 1 month after discharge, all-cause and cause-specific mortality, frequency of AECOPD recurrence, lung function, life quality, healthcare costs in the study period, etc.

9.
Int J Pharm ; 585: 119513, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32526334

RESUMO

The RNA-cleaving DNAzyme (DZ) holds promising potential for RNA interference (RNAi) applications and is favored over siRNA owing to its high chemical stability, biocompatibility, predictable activity, and substrate versatility. However, its pharmaceutical applications for disease treatment are limited by the requirement of metal cofactor for activation, as well as the lack of effective co-delivery systems to combine with other therapeutic modalities. Herein, we designed and constructed metal organic framework (MOF) coated MnO2 nanosheets to realize the co-delivery of a survivin inhibiting DZ and doxorubicin (DOX) for chemo-gene combinatorial treatment of cancer. In our design, the DOX was adsorbed on MnO2 planar surface, and the DZ was loaded into the MOF shell layer through the coordination between Mn2+ and tannic acid. The nano-system could stably encapsulate the payloads under physiological condition, but rapidly degraded after endocytose into tumor cells in response to intracellular stimuli, resulting in triggered drugs release. Notably, the coreleased Mn2+ could act as metal cofactor for effective DZ activation. Both in vitro and in vivo studies have demonstrated the enhanced anti-tumor efficacy of the nanosystem, with co-contributions from anti-neoplastic DOX, survivin silencing effect of DZ, and to some extent, ROS generation by Mn2+. This work provides an ingenious strategy to address the key limitation of DZ for RNAi applications and realize the combination of DZ with other therapeutic modalities, in which the DZ can be in-situ activated for target gene silencing.

10.
Environ Res ; 186: 109578, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32380244

RESUMO

BACKGROUND: Carcinogens released from indoor burning of solid fuels are believed to enter the bloodstream and to be metabolized in breast and cervical tissues. Little evidence exists about the relationship of solid fuel use from heating with breast and cervical cancer. OBJECTIVES: To examine the association of solid heating fuel use with breast and cervical cancer mortality. METHODS: This study included female participants aged 30-79 years who were enrolled in the China Kadoorie Biobank during 2004-2008 from 10 diverse regions across China. During a 10.2-year median follow-up, 177 breast cancer deaths and 113 cervical cancer deaths were documented. Multivariable Cox regression models yielded adjusted hazard ratios (HRs) for the associations of self-reported long-term heating fuel exposure with two cancer deaths. Stratified analyses were used to assess effect modification. RESULTS: We included 236,116 participants for breast cancer analyses and 228,795 for cervical cancer analyses. Compared with non-solid fuel use, the fully adjusted HRs of cervical cancer deaths were 1.75 (0.91-3.38) for wood use, 2.23 (1.09-4.59) for mixed fuel (coal and wood) use. No evident relationship was observed for breast cancer deaths. Cervical cancer risk increased with the duration of solid fuel use (P for trend = 0.041). Elevated cervical cancer risk was observed in post-menopausal women (HR 2.01, 1.01-4.03), not in pre-menopausal women (HR 0.77, 0.56-2.31) (P for heterogeneity = 0.004); and in those aged ≥50 years (HR 2.56, 1.17-5.86), not in those aged < 50 years (HR 0.69, 0.26-1.84) (P < 0.001). CONCLUSION: Indoor solid fuel combustion for heating may be associated with a higher risk for cervical cancer death, but not for breast cancer. The strength of the association increased with the duration of exposure and was modified by age and menopause status.


Assuntos
Poluição do Ar em Ambientes Fechados , Neoplasias do Colo do Útero , Adulto , Idoso , China/epidemiologia , Carvão Mineral , Culinária , Feminino , Calefação , Humanos , Pessoa de Meia-Idade
11.
Artigo em Inglês | MEDLINE | ID: mdl-32325946

RESUMO

Background: The association between smoking and blood pressure (BP) has been explored extensively, yet the results remain inconclusive. Using real-world evidence of a large Chinese population, we examine the effect of smoking on BP levels. Methods: We utilize half a million adults from the China Kadoorie Biobank (CKB) study with baseline sampling collected between 2004 and 2008. Multivariable linear regression analyses are used to estimate linear regression coefficients of smoking for systolic blood pressure (SBP) and diastolic blood pressure (DBP). Results: 459,815 participants (180,236 males and 279,579 females) are included in the analysis. Regular smoking is significantly associated with lower SBP (-0.57 mm Hg, p < 0.001) and DBP (-0.35 mm Hg, p < 0.001) when compared with non-smoking in men. Additionally, SBP and DBP decrease significantly among all groups of different smoking status in women (p < 0.001). Additionally, pack-years show negative associations with SBP and DBP in both men and women. Further analysis shows the interaction of smoking and alcohol consumption is associated with an increase of SBP and DBP (men: 2.38 mm Hg and 0.89 mm Hg; women: 5.21 mm Hg and 2.62 mm Hg) among co-regular smokers and regular drinkers when compared with regular smokers who are not exposed to alcohol consumption. Conclusions: A negative association between smoking and BP is observed. However, the interaction between smoking and alcohol consumption is associated with BP increase. The findings suggest the importance of considering smoking and alcohol consumption in BP control in addition to antihypertensive treatment in clinical and public health practice.


Assuntos
Pressão Sanguínea , Fumar/efeitos adversos , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
J Neurol Neurosurg Psychiatry ; 91(5): 520-525, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32139654

RESUMO

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease and information on disease burden of ALS in mainland China was limited. We aimed to estimate the prevalence and incidence of ALS in China. METHODS: We used 2012-2016 data from China's Urban Employee Basic Medical Insurance and Urban Residence Basic Medical Insurance, covering approximately 0.43 billion individuals. ALS cases were identified by the primary diagnosis (International Classification of Diseases code or text of diagnosis) in the insurance database. RESULTS: The crude prevalence and incidence in 2016 were 2.91 per 100 000 person-years (95% CI 2.31 to 3.58) and 1.65 (95% CI 1.33 to 2.01), respectively. The standardised prevalence and incidence based on 2010 Chinese census data were 2.97 (95% CI 2.91 to 3.03) and 1.62 (95% CI 1.58 to 1.67), respectively. The annual prevalence between 2013 and 2016 remained relatively constant, ranging from 2.91 (95% CI 2.31 to 3.58) in 2016 to 3.29 (95% CI 2.51 to 4.17) in 2014 (linear regression: ß=-0.129, p=0.104). Both rates peaked in the group aged 75-79 years. CONCLUSIONS: The prevalence and incidence of ALS in mainland China were lower than those in developed countries, and maintained a relatively stable trend. The age at onset and age at diagnosis for ALS patients were younger than those in developed countries. Further research is expected to clarify the potential pathophysiological mechanism of ALS.


Assuntos
Esclerose Amiotrófica Lateral/epidemiologia , População Urbana/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores Sexuais , Adulto Jovem
13.
J Neurol ; 267(4): 944-953, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31797084

RESUMO

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a global disease, which adversely affects the life quality of patients and significantly increases the burden of families and society. We aimed to assess the changing incidence, prevalence of ALS around the world. METHODS: We searched Medline, Embase, Web of Science, and Cochrane library to identify articles published until September 9, 2018. Each included study was independently reviewed for methodological quality by two reviewers. We used a random-effects model to summarize individual studies and assessed heterogeneity (I2) with the χ2 test on Cochrane's Q statistic. RESULTS: We identified 124 studies that were eligible for final inclusion, including 110 studies of incidence and 58 studies of prevalence. The overall crude worldwide ALS prevalence and incidence were 4.42 (95% CI 3.92-4.96) per 1,00,000 population and 1.59 (95% CI 1.39-1.81) per 1,00,000 person-years, respectively. ALS prevalence and incidence increased by age until the age of 70-79. Since 1957, incidence has been significantly rising year by year, and this upward trend was weakened after standardization. The longest survival time were in Asia (ranging from 3.74 years in South Asia to 9.23 years in West Asia). CONCLUSIONS: With the aggravation of population aging and the rapid growth of economy, developing regions following the development pattern of the developed regions may suffer rising ALS prevalence and incidence which may increase their disease burden as well. These data highlight the need for research into underlying mechanism and innovations in health-care systems.

14.
Mikrochim Acta ; 186(12): 824, 2019 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-31754805

RESUMO

The authors describe a tetrahedral DNA nanostructure loaded with SYBR Green (SG-TDN) for fluorometric determination of nucleic acids. After intercalating into the TDN, fluorescence of SG is enhanced by 260-fold (exc 480 nm, em 524 nm), and the resulting SG-TDN nanoflare displays >7-fold stronger fluorescence than that of FAM-labeled TDN. The SG-TDNs were coupled to magnetic microparticles and polydopamine nanoparticles to construct multi-functional nanoprobes through sequence hybridization using a toehold strand. The method was applied to detect a stretch of microRNA sequence (20 bp) in buffer and in undiluted serum with excellent selectivity, over a wide linear range and with a low limit of detection (0.2 nM). The probe was also applied for visualization of tumor-related microRNA in living cells via fluorescence imaging. Graphical abstract Schematic representation of tetrahedron-based DNA nanoflare for fluorometric nucleic acid determination in undiluted blood serum and living cells.


Assuntos
Corantes Fluorescentes/química , Substâncias Intercalantes/química , Nanoestruturas/química , Ácidos Nucleicos/química , Células A549 , Técnicas Biossensoriais , DNA/química , Fluorometria , Células HEK293 , Humanos , Indóis , Limite de Detecção , MicroRNAs/química , Hibridização de Ácido Nucleico , Imagem Óptica , Polímeros , Sensibilidade e Especificidade
15.
Twin Res Hum Genet ; 22(6): 482-485, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31708009

RESUMO

The Chinese National Twin Registry (CNTR), initiated in 2001, has now become the largest twin registry in Asia. From 2015 to 2018, the CNTR continued to receive Chinese government funding and had recruited 61,566 twin-pairs by 2019 to study twins discordant for specific exposures such as environmental factors, and twins discordant for disease outcomes or measures of morbidity. Omic data, including genetics, genomics, metabolomics, and proteomics, and gut microbiome will be tested. The integration of omics and digital technologies in public health will advance our understanding of precision public health. This review introduces the updates of the CNTR, including study design, sample size, biobank, zygosity assessment, advances in research and future systems epidemiologic research.

16.
Analyst ; 144(17): 5098-5107, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31373344

RESUMO

Simultaneous detection and regulation of tumor-related genes presents a promising strategy for early diagnosis and treatment of cancer, but achieving this has been a huge challenge for both chemical and biomedical communities. Towards this objective, we have devised a novel aptamer-tethered, DNAzyme-embedded molecular beacon (MB) for multiple functions in cancer cells. In this design, a tumor targeting aptamer was employed to specifically deliver the sensor into cancer cells for target gene detection, and an RNA-cleaving DNAzyme was embedded to realize gene regulation. Both aptamer-tethering and DNAzyme-embedding had little influence on the sensor performance, with a detection limit of ∼2 nM and high specificity. After delivering into tumor cells, our device could monitor the tumor-related genes by producing detectable fluorescence signals, and regulate the gene expression at both mRNA and protein levels as evidenced by the RT-PCR and western blot analyses. This study provides a simple and efficient strategy to rationally combine various functional nucleic acids for multi-functional applications in living cells, which hold great potential for cancer diagnosis and therapy.


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , DNA Catalítico/química , Genes Neoplásicos , Linhagem Celular Tumoral , Humanos , Limite de Detecção
17.
Pharmacoepidemiol Drug Saf ; 28(11): 1501-1509, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31397051

RESUMO

PURPOSE: To explore treatment patterns among patients with prostate cancer and bone metastasis and to compare clinical outcomes following use of different hormone therapies including combined androgen blockade (CAB), nonsteroidal antiandrogen (NSAA) monotherapy, and castration monotherapy. METHODS: We conducted a population-based cohort study using data from the Urban Employee Basic Medical Insurance database (2011-2014) in Beijing. We identified 475 patients with newly diagnosed bone metastatic prostate cancer with at least one prescription for hormone therapy and described their treatment patterns over a median follow-up of 20.7 months. Cox proportional hazards model was used to compare time to chemotherapy initiation between patients starting on different hormone therapies. RESULTS: Hormone therapy and/or bisphosphonate therapy with zoledronic acid were the initial treatments in the majority of patients (87.8%); chemotherapy, radiotherapy, and surgery were usually given later in the treatment pathway. CAB was the most common hormone treatment (73.7%). For time to chemotherapy initiation, hazard ratios (95% confidence intervals) were 2.43 (1.08-5.44) for NSAA alone vs CAB and 1.29 (0.78-2.13) for castration alone vs CAB. CONCLUSIONS: Our findings show that while a wide range of therapies are used to treat patients with prostate cancer and bone metastasis in Beijing, hormone therapy and bisphosphonate therapy are the most commonly prescribed, and use of CAB was seen to be advantageous in delaying time to chemotherapy initiation over NSAA monotherapy. Future studies should explore longer-term treatment patterns, including use of newly approved treatments.

18.
BMC Complement Altern Med ; 19(1): 138, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221141

RESUMO

BACKGROUND: Oxymatrine (OM), a quinolizidine alkaloid extracted from a herb Sophorae Flavescentis Radix, has been used to treat liver fibrotic diseases. However, the mechanism of its anti-fibrosis effects is still unclear. TGF-ß/Smad signaling and miR-195 have been proved to paly an important role in hepatic stellate cells (HSCs) activation and liver fibrosis. In this study, we investigated whether OM could inhibit HSCs activation through TGF-ß1/miR-195/Smads signaling or not. METHODS: First, the effects of OM on HSC-T6 in different concentrations and time points were tested by MTT assay. We choose three appropriate concentrations of OM as treatment concentrations in following experiment. By Quantitative Real-time PCR and Western Blot, then we investigated the effect of OM on miR-195, Smad7 and α-SMA's expressions to prove the correlation between OM and the TGF-ß1/miR-195/Smads signaling. Last, miR-195 mimic and INF-γ were used to investigate the relation between miR-195 and OM in HSC activation. RESULTS: Our results showed that the proliferation of HSC was significantly inhibited when OM concentration was higher than 200 µg/mL after 24 h, 100 µg/mL after 48 h and 10 µg/mL after 72 h. The IC50 of OM after 24, 48 and 72 h were 539, 454, 387 µg/mL respectively. OM could down-regulate miR-195 and α-SMA (P < 0.01), while up-regulate Smad7 (P < 0.05). In HSC-T6 cells transfected with miR-195 mimic and pretreated with OM, miR-195 and α-SMA were up-regulated (P < 0.05), and Smad7 was down-regulated (P < 0.05) . CONCLUSIONS: Given these results, OM could inhibit TGF-ß1 induced activation of HSC-T6 proliferation in a dose-dependent and time-dependent manner to some extent. We proved that OM inhibited HSC activation through down-regulating the expression of miR-195 and up-regulating Smad7.


Assuntos
Alcaloides/farmacologia , Células Estreladas do Fígado/efeitos dos fármacos , MicroRNAs/metabolismo , Extratos Vegetais/farmacologia , Quinolizinas/farmacologia , Proteína Smad7/metabolismo , Sophora/química , Fator de Crescimento Transformador beta1/metabolismo , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Humanos , Interferon gama/genética , Interferon gama/metabolismo , MicroRNAs/genética , Ratos , Transdução de Sinais/efeitos dos fármacos , Proteína Smad7/genética , Fator de Crescimento Transformador beta1/genética
19.
Int J Cancer ; 145(12): 3321-3333, 2019 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-31173346

RESUMO

Somatic mutation signatures may represent footprints of genetic and environmental exposures that cause different cancer. Few studies have comprehensively examined their association with germline variants, and none in an indigenous African population. SomaticSignatures was employed to extract mutation signatures based on whole-genome or whole-exome sequencing data from female patients with breast cancer (TCGA, training set, n = 1,011; Nigerian samples, validation set, n = 170), and to estimate contributions of signatures in each sample. Association between somatic signatures and common single nucleotide polymorphisms (SNPs) or rare deleterious variants were examined using linear regression. Nine stable signatures were inferred, and four signatures (APOBEC C>T, APOBEC C>G, aging and homologous recombination deficiency) were highly similar to known COSMIC signatures and explained the majority (60-85%) of signature contributions. There were significant heritable components associated with APOBEC C>T signature (h2 = 0.575, p = 0.010) and the combined APOBEC signatures (h2 = 0.432, p = 0.042). In TCGA dataset, seven common SNPs within or near GNB5 were significantly associated with an increased proportion (beta = 0.33, 95% CI = 0.21-0.45) of APOBEC signature contribution at genome-wide significance, while rare germline mutations in MTCL1 was also significantly associated with a higher contribution of this signature (p = 6.1 × 10-6 ). This is the first study to identify associations between germline variants and mutational patterns in breast cancer across diverse populations and geography. The findings provide evidence to substantiate causal links between germline genetic risk variants and carcinogenesis.


Assuntos
Afro-Americanos/genética , Neoplasias da Mama/genética , Grupo com Ancestrais do Continente Europeu/genética , Mutação em Linhagem Germinativa/genética , Polimorfismo de Nucleotídeo Único/genética , Idoso , Exoma/genética , Feminino , Predisposição Genética para Doença , Genoma Humano/genética , Humanos , Pessoa de Meia-Idade , Nigéria , Estados Unidos , Sequenciamento Completo do Exoma/métodos
20.
J Proteomics ; 199: 123-134, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30849524

RESUMO

Zinc (Zn) deficiency reduces chlorophyll content and damages chloroplast structure in leaves. However, little is known about the responses of chlorophyll synthesis and chloroplast structure of plants to Zn deficiency stress at the transcriptomic and proteomic level. In the present study, maize seedlings of cultivar ZD958 were grown in nutrient solution with 0 and 1.0 µmol·L-1 Zn treatments. Zn deficiency stress reduced photosynthetic rate at 10 and 15 days after treatment (DAT) and the chlorophyll content (SPAD value) at 15 DAT. Eight differentially expressed genes and 6 differential abundance proteins were involved in chlorophyll biosynthetic process in Zn deficient leaves. Genes related with the key enzymes catalyzing the chlorophyll synthesis including magnesium-chelatase subunit ChlH chloroplastic, magnesium protoporphyrin IX methyltransferase chloroplastic showed down-regulated trend by Zn deficiency at the transcriptome or proteome levels. The defective chloroplast structure of Zn-deficient leaves showed less grana granule and loose membrane. Seven changed genes in transcriptome profile were assigned to thylakoid membrane organization in Zn-deficient leaves while 8 differential abundance proteins in proteome data. The expression of the genes related with thylakoid membrane organization process such as protein PHOTOSYSTEM I ASSEMBLY 2, chloroplastic were down-regulated under limited Zn deficiency at both transcriptome and proteome levels.


Assuntos
Folhas de Planta/metabolismo , Zea mays/metabolismo , Zinco/deficiência , Clorofila/biossíntese , Cloroplastos/ultraestrutura , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Folhas de Planta/ultraestrutura , Proteômica , Estresse Fisiológico , Zea mays/ultraestrutura , Zinco/farmacologia
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