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1.
BMJ Paediatr Open ; 8(1)2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38631844

RESUMO

OBJECTIVE: To identify determinants of the utilisation of ophthalmic clinical health services among students who failed school vision screening. METHODS: This study employed a sequential explanatory mixed methods design, underpinned by Andersen's Behavioural Model of Health Service Utilisation. Data were initially gathered through interviews with 27 stakeholders-comprising 5 ophthalmologists, 7 community doctors, 7 public health professionals and 8 teachers. The qualitative insights informed the construction of a questionnaire, which subsequently garnered responses from 6215 participants. Qualitative data underwent thematic analysis with NVivo V.12, while quantitative data were analysed using multivariable multinomial logistic regression in SAS V.9.4. Data integration was performed using the Pillar Integration Process for a deductive, evidence-based synthesis of findings. RESULTS: The research revealed that students attending vision demonstration schools and receiving encouragement from schools or communities to access clinical ophthalmic services demonstrated higher adherence to referral (OR=1.66, 95% CI 1.30 to 2.12; OR=1.54, 95% CI 1.33 to 1.80). Conversely, older students and those from higher-income families exhibited lower adherence rates (OR=0.31, 95% CI 0.23 to 0.44; OR=0.34, 95% CI 0.25 to 0.46). Moreover, students with less urgent medical needs were more likely to adhere to referrals compared with those needing immediate referrals (OR=1.24, 95% CI 1.06 to 1.45).Four pillars emerged: (a) adherence decreased with age, (b) financial constraints did not pose an obstacle, (c) public health services played a critical role, (d) referral urgency did not linearly correlate with adherence. CONCLUSION: The utilisation of ophthalmic clinical health services following vision screening failure in students is significantly influenced by public health services provided by schools or communities, such as prompting those with abnormal screening results to access ophthalmic clinical health services.


Assuntos
Seleção Visual , Humanos , Atenção à Saúde , Aceitação pelo Paciente de Cuidados de Saúde , Instituições Acadêmicas , Serviços de Saúde
2.
JACC Clin Electrophysiol ; 9(8 Pt 2): 1455-1463, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37269285

RESUMO

BACKGROUND: In arrhythmogenic right ventricular cardiomyopathy (ARVC) patients with extensive right ventricular free wall (RVFW) abnormal substrate, large-area homogenization with combined epicardial and endocardial approach is time consuming and often inadequate for modification. OBJECTIVES: This study aimed to explore the feasibility and efficacy of RVFW abnormal substrate isolation in such patients to control ventricular tachycardia (VT). METHODS: Eight consecutive ARVC patients with VT who had extensive abnormal RVFW substrate were included. VT induction was performed before substrate mapping and modification. Detailed voltage mapping was done during sinus rhythm. A circumferential linear lesion was deployed along the border zone of low-voltage area on the RVFW to achieve electrical isolation. Other small areas with fractionated or late potentials were further homogenized. RESULTS: All 8 patients had RVFW endocardial low-voltage area. The entire RV low-voltage area was 113.8 ± 84.1 cm2 (49.6% ± 29.8%) and the dense scar was 59.6 ± 39.8 cm2 (25.0% ± 14.1%). Electrical isolation of abnormal substrate was achieved in 5 of 8 (62.5%) patients via endocardial approach alone and 3 of 8 (37.5%) patients via a combination of endocardial and epicardial approach. Electrical isolation was verified by slow automaticity (5 of 8, 62.5%) or RV noncapture (3 of 8, 37.5%) during high-output pacing inside the encircled area. VTs were induced in 6 patients before ablation, and all patients were rendered noninducible after ablation. During a median follow-up of 43 months (range: 24-53 months), 7 of 8 (87.5%) patients remained free of sustained VT. CONCLUSIONS: Electrical isolation of RVFW is feasible and can be the option in ARVC patients with extensive abnormal substrate.


Assuntos
Displasia Arritmogênica Ventricular Direita , Ablação por Cateter , Taquicardia Ventricular , Humanos , Displasia Arritmogênica Ventricular Direita/complicações , Displasia Arritmogênica Ventricular Direita/cirurgia , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/cirurgia , Taquicardia Ventricular/patologia , Endocárdio , Potenciais de Ação
3.
Circ J ; 87(7): 964-972, 2023 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-37225477

RESUMO

BACKGROUND: Previous studies revealed a relationship between 8-hydroxy-2'-deoxyguanosine (8-OHdG) and the occurrence/recurrence of atrial fibrillation (AF). This 2-part study aimed to validate whether DNA damage related to 8-OHdG is associated with left atrial (LA) fibrosis in AF patients quantified by voltage mapping (Part I), and to identify the underlying genetic components regulating the 8-OHdG level (Part II).Methods and Results: Plasma 8-OHdG determination, DNA extraction, and genotyping were conducted before catheter ablation. LA voltage mapping was performed under sinus rhythm. According to the percentage of low voltage area (LVA), patients were categorized as stage I (<5%), stage II (5-10%), stage III (10-20%), and stage IV (>20%). Part I included 209 AF patients. The 8-OHdG level showed an upward trend together with advanced LVA stage (stage I 8.1 [6.1, 10.5] ng/mL, stage II 8.5 [5.7, 14.1] ng/mL, stage III 14.3 [12.1, 16.5] ng/mL, stage IV 13.9 [10.5, 16.0] ng/mL, P<0.000). Part II included 175 of the 209 patients from Part I. Gene-set analysis based on genome-wide association study summary data identified that the gene set named 'DNA methylation on cytosine' was the only genetic component significantly associated with 8-OHdG concentration. CONCLUSIONS: Higher 8-OHdG levels may predict more advanced LVA of the LA in AF patients. DNA methylation is the putative genetic component underlying oxidative DNA damage in AF patients.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Humanos , 8-Hidroxi-2'-Desoxiguanosina , Metilação de DNA , Estudo de Associação Genômica Ampla , Átrios do Coração , Biomarcadores , Fibrose , Ablação por Cateter/métodos , Recidiva , Resultado do Tratamento
4.
Pacing Clin Electrophysiol ; 46(7): 752-760, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37221974

RESUMO

BACKGROUND: It is inevitable for patients to have a temporary or permanent pacemaker implanted during or after radiofrequency catheter ablation (RFCA) for treatment of atrial fibrillation (AF) in some cases. The aim of our study was to evaluate the incidence of pacemaker implantation (PMI) during or within 3 months of RFCA for AF and to identify the risk factors that were associated with PMI. METHODS: We performed a retrospective analysis of consecutive AF patients who underwent RFCA between August 2018 and October 2020 at our center. The incidence of PMI within 3 months during or after RFCA were assessed. A multivariate logistic regression model was performed to identify predictors of PMI. RESULTS: One thousand and five patients (mean age, 60.2 ± 10.3 years; 37.6% women) were included in this analysis. PVI was performed in all patients. A total of 23 (2.3%) patients had a pacemaker implanted within 3 months during or after ablation. Multivariable logistic regression analysis revealed that older age (OR: 1.08 [95% CI 1.03-1.13], p = .003), female sex (OR: 3.08 [95% CI 1.28-7.45], p = .012), paroxysmal AF (OR: 4.71 [95% CI 1.09-20.45], p = .038) and repeated ablation (OR: 2.78 [95% CI 1.04-7.40], p = .041) were the independent predictors for PMI. CONCLUSIONS: Older age, female sex, paroxysmal AF and repeated ablation were identified as predictive risk factors for PMI after RFCA in patients with AF. A "watch and wait" strategy could be taken for patients with temporary PMI after ablation, especially for those with prolonged sinus pause after AF termination.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Marca-Passo Artificial , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Ablação por Cateter/efeitos adversos , Recidiva
5.
Clin Appl Thromb Hemost ; 29: 10760296231168097, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37079758

RESUMO

To assess the prevalence and management of atrial thrombus in patients with nonvalvular atrial fibrillation (NVAF) and identify the risk factors of the nonresolution of atrial thrombus. This single-center retrospective observational study consecutively enrolled patients with NVAF and atrial thrombus detected using transesophageal echocardiography (TEE) or cardiac computed tomography angiography (CTA) from January 2012 to December 2020. Patients with prior left atrial appendage (LAA) intervention were excluded. The primary endpoint was the presence of atrial thrombus, while the secondary endpoint was the complete resolution of atrial thrombus. The prevalence of atrial thrombus in patients with NVAF was 1.4%. Ninety patients with atrial thrombus (mean age 62.8 ± 11.9 years and 61.1% men) were finally analyzed. Atrial thrombus was in the LAA in 82 (91.1%) patients. During follow up, 60% of the patients showed complete resolution of atrial thrombus. Congestive heart failure (odds ratio [OR]: 8.94; 95% confidence interval [CI]: 1.67-47.80) and a history of ischemic stroke (OR: 8.28; 95% CI: 1.48-46.42) were independently associated with the risk of the nonresolution of atrial thrombus. The presence of atrial thrombus in patients with NVAF who received anticoagulation therapy is non-negligible. Even in anticoagulated patients, TEE or cardiac CTA might still be needed. Congestive heart failure and a history of ischemic stroke are risk factors of the nonresolution of atrial thrombus.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Cardiopatias , Insuficiência Cardíaca , AVC Isquêmico , Trombose , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Fibrilação Atrial/tratamento farmacológico , Apêndice Atrial/diagnóstico por imagem , Cardiopatias/complicações , Cardiopatias/tratamento farmacológico , Trombose/tratamento farmacológico , Ecocardiografia Transesofagiana , AVC Isquêmico/tratamento farmacológico , Insuficiência Cardíaca/complicações , Anticoagulantes/uso terapêutico
6.
J Digit Imaging ; 36(2): 441-449, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36474087

RESUMO

Cervical cancer is the most common cancer among women worldwide. The diagnosis and classification of cancer are extremely important, as it influences the optimal treatment and length of survival. The objective was to develop and validate a diagnosis system based on convolutional neural networks (CNN) that identifies cervical malignancies and provides diagnostic interpretability. A total of 8496 labeled histology images were extracted from 229 cervical specimens (cervical squamous cell carcinoma, SCC, n = 37; cervical adenocarcinoma, AC, n = 8; nonmalignant cervical tissues, n = 184). AlexNet, VGG-19, Xception, and ResNet-50 with five-fold cross-validation were constructed to distinguish cervical cancer images from nonmalignant images. The performance of CNNs was quantified in terms of accuracy, precision, recall, and the area under the receiver operating curve (AUC). Six pathologists were recruited to make a comparison with the performance of CNNs. Guided Backpropagation and Gradient-weighted Class Activation Mapping (Grad-CAM) were deployed to highlight the area of high malignant probability. The Xception model had excellent performance in identifying cervical SCC and AC in test sets. For cervical SCC, AUC was 0.98 (internal validation) and 0.974 (external validation). For cervical AC, AUC was 0.966 (internal validation) and 0.958 (external validation). The performance of CNNs falls between experienced and inexperienced pathologists. Grad-CAM and Guided Gard-CAM ensured diagnoses interpretability by highlighting morphological features of malignant changes. CNN is efficient for histological image classification tasks of distinguishing cervical malignancies from benign tissues and could highlight the specific areas of concern. All these findings suggest that CNNs could serve as a diagnostic tool to aid pathologic diagnosis.


Assuntos
Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/diagnóstico por imagem , Redes Neurais de Computação , Colo do Útero
7.
J Environ Manage ; 325(Pt B): 116522, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36306625

RESUMO

Green bonds are becoming increasingly important in sustainable investments since their environmental protection attributes allow them to benefit from environmental degradation. However, the mechanism of environmental degradation on green bonds has not yet been studied. This study proposes a mediation model to analyze air pollution's influence on green bonds. Theoretically, air pollution leads to increased public concern through public environmental awareness and perceptions of physical health risks. Enhanced public concern drives investors' green preference and environmental responsibility, thus expanding green bond demand, in which public concern plays an important mediation role. To verify the mediating effect, causal stepwise regression and bootstrap methods are used. The empirical results confirm this theoretical mechanism. Air pollution is significantly positively related to public concern. Public concern is positively linked with green bond investment willingness, resulting in increased volatility. The total positive effect of air pollution on green bonds is partly absorbed by the mediating effect of public concern that is significantly positive and reaches 30.21% of the total effect. In addition, major crisis events (e.g., COVID-19) may hinder the positive mediation process by generating a negative trend and distracting the public. This means that the government could propose appropriate measures to minimize the negative aspects in order to promote green finance. The mediation model is also useful for investors wishing to increase green assets in their portfolios and provides an incentive for businesses to promote green finance.


Assuntos
Poluição do Ar , COVID-19 , Humanos , Poluição do Ar/prevenção & controle , Conservação dos Recursos Naturais , Governo , China
8.
Chinese Journal of School Health ; (12): 1333-1337, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-988856

RESUMO

Objective@#To develop an assessment questionnaire for screen based behaviors among primary and secondary school students, so as to provide a basis for comprehensive assessment among the population.@*Methods@#Nineteen experts were invited to take part in this study from August to September 2022. The initial framework and item pool of the assessment questionnaire were developed based on literature review and a series of guidelines and standards issued by the national education and health authorities, as well as relevant domestic and foreign guidelines, and were combined with existing assessment tools that were used to evaluate screen based behavior among these age groups. Experts in related fields were selected for two rounds of Delphi consultation to determine the dimensions, items and corresponding weights of the assessment questionnaire.@*Results@#The response rates from two rounds of consultation were 95.0% and 100.0% respectively, the opinion submission rates were 89.5% and 63.2% respectively, and the authority coefficient ( Cr ) was 0.87. An assessment questionnaire was finally designed, consisting in 44 items and four dimensions, namely screen use type and time, screen use related health behaviors, safety and civilization in screen use, and reasonable arrangement of screen and non screen activities. The coefficient of variation( CV ) of each item ranged from 0.00 to 0.19, and the Kendall s W increased from 0.22 to 0.34( P <0.01). Expert opinions were in agreement and credible.@*Conclusion@#The designed assessment questionnaire can be used to comprehensively evaluate screen based behavior among primary and middle school students, and provides a basis for subsequent intervention measures to improve screen based behavior among this population.

9.
Pharm Biol ; 60(1): 2229-2236, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36367996

RESUMO

CONTEXT: Ginsenoside Rb1 (Rb1) is a biologically active component of ginseng [Panax ginseng C.A. Meyer (Araliaceae)]. OBJECTIVE: This study determined the underlying mechanisms of Rb1 treatment that acted on diabetes-injured lungs in diabetic rats. MATERIALS AND METHODS: Streptozotocin (STZ)-induced diabetic rat model was used. Male Sprague-Dawley (SD) rats were divided into four groups (n = 10): control, Rb1 (20 mg/kg), insulin (15 U/kg to attain the euglycaemic state) and diabetic (untreated). After treatment for six weeks, oxidative stress assay; histological and ultrastructure analyses; TNF-α, TGF-ß, IL-1 and IL-6 protein expression analyses; and the detection of apoptosis were performed. RESULTS: There was decreased activity of SOD (3.53-fold), CAT (2.55-fold) and GSH (1.63-fold) and increased levels of NO (4.47-fold) and MDA (3.86-fold) in the diabetic group from control. Rb1 treatment increased SOD (2.4-fold), CAT (1.9-fold) and GSH (1.29-fold) and decreased the levels of NO (1.76-fold) and MDA (1.51-fold) as compared with diabetic rats. The expression of IL-6 (5.13-fold), IL-1α (2.35-fold), TNF-α (2.35-fold) and TGF-ß (2.39-fold) was increased in diabetic rats from control. IL-6 (2.43-fold), IL-1α (2.27-fold), TNF-α (1.68-fold) and TGF-ß (2.3-fold) were decreased in the Rb1 treatment group. Diabetes increased the apoptosis rate (2.23-fold vs. control), and Rb1 treatment decreased the apoptosis rate (1.73-fold vs. the diabetic rats). Rb1 and insulin ameliorated lung tissue injury. DISCUSSION AND CONCLUSIONS: These findings indicate that Rb1 could be useful for mitigating oxidative damage and inflammatory infiltration in the diabetic lung.


Assuntos
Diabetes Mellitus Experimental , Ginsenosídeos , Panax , Ratos , Masculino , Animais , Estreptozocina , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/induzido quimicamente , Fator de Necrose Tumoral alfa , Interleucina-6 , Ratos Sprague-Dawley , Ginsenosídeos/farmacologia , Estresse Oxidativo , Inflamação/tratamento farmacológico , Panax/química , Pulmão , Insulina , Fator de Crescimento Transformador beta , Superóxido Dismutase
10.
Vasc Health Risk Manag ; 18: 757-766, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36133642

RESUMO

China has a large population of elderly in rural areas. Village doctors are acting as health-care gatekeepers for the rural elderly in China and are encouraged to provide more long-term care for patients with chronic diseases such as atrial fibrillation (AF). The data of AF registries from the rural elderly are limited. The present registry aims to provide contemporary data on the current AF-related health status of the rural elderly and the gaps in management of AF by village doctors. This study has two phases. The first phase is a cross-sectional study of AF screening in two rural towns of eastern China. All the residents aged ≥65 years are eligible and will be invited to attend a government-led health examination or an in-house AF screening program. The AF detection rate, the awareness of AF and the usage of oral anticoagulants and smartphones by AF patients, and the ability to diagnose and manage AF by village doctors will be assessed. Participants with AF detected in the first phase are eligible for the second phase. A variety of modes of intensified education will be provided to all AF patients and their family members to enrich their AF-related knowledge. Their village doctors will be offered a lecture-based training program focusing on Atrial fibrillation Better Care (ABC) pathway. Follow-up will be conducted for 1 year. The primary endpoint is the composite of all stroke and all-cause mortality. The first phase of AF screening was conducted between April 2019 and June 2019, and 18,712 participants with the mean age of 73.1±5.8 years were enrolled. The second phase that includes 810 patients with AF, started on 1 May 2019. This study will provide a perspective of primary care system and would indirectly reflect the current status of chronic disease care in rural China.


Assuntos
Fibrilação Atrial , Idoso , Anticoagulantes , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/terapia , China/epidemiologia , Estudos Transversais , Humanos , População Rural
11.
Quant Imaging Med Surg ; 12(7): 3592-3602, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35782252

RESUMO

Background: Syncope is common, but there is no clear cause for half of the patients diagnosed with syncope. Although suspected, there is limited evidence that right-to-left shunt (RLS) is related to syncope. This matched case-control study investigated the association between RLS (exposure) and unexplained syncope (outcome). Methods: Consecutive unexplained syncope cases, together with age- and gender-matched controls who did not have syncope were recruited from 2009 to 2010 in the first affiliated hospital of Nanjing Medical University. A transcranial Doppler ultrasonography bubble test was applied for the ascertainment of RLS. The degree of RLS was categorized into grades 0 to 4 according to the number of microemboli, which were no shunt, <10 microbubbles (MB), 11-25 MB, >25 MB single spots pattern, and MB in a shower/curtain pattern, respectively. Cerebral small vessel diseases (SVD), including white matter hyperintensity, lacunes, and enlarged perivascular spaces, were rated on Magnetic resonance imaging. Conditional logistic regression was used to examine the association between RLS and unexplained syncope. Results: A total of 52 cases and 52 age- and gender-matched controls were recruited. Among the 52 cases, 4 patients had a history of migraine. Among the 104 participants, 68 had no RLS; 13, 4, 7, and 12 presented with <10, 11-25, >25, and shower/curtain MB, respectively. The incidence of any RLS (Grade 1-4) was 48.1% (25/52) in cases and 21.2% (11/52) in controls (P=0.004). Conditional logistic regression showed an association between RLS and unexplained syncope [odds ratio (OR) =1.988; 95% confidence interval (CI): 1.233 to 3.205; P=0.005] adjusting for SVD burden. Further analysis revealed a large OR between severe RLS (Grade 3-4) and unexplained syncope (OR =8.699; P=0.006). Furthermore, SVD burden was shown to be associated with syncope. Conclusions: This matched case-control study showed a significant association between RLS and unexplained syncope, independent of cerebral SVD. Prospective studies are needed to confirm the causal relationship.

12.
Heart Rhythm ; 19(11): 1781-1789, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35843464

RESUMO

BACKGROUND: Precise localization of the site of origin of premature ventricular contractions (PVCs) before ablation can facilitate the planning and execution of the electrophysiological procedure. OBJECTIVE: The purpose of this study was to develop a predictive model that can be used to differentiate PVCs between the left ventricular outflow tract and right ventricular outflow tract (RVOT) using surface electrocardiogram characteristics. METHODS: A total of 851 patients undergoing radiofrequency ablation of premature ventricular beats from January 2015 to March 2022 were enrolled. Ninety-two patients were excluded. The other 759 patients were enrolled into the development (n = 605), external validation (n = 104), or prospective cohort (n = 50). The development cohort consisted of the training group (n = 423) and the internal validation group (n = 182). Machine learning algorithms were used to construct predictive models for the origin of PVCs using body surface electrocardiogram features. RESULTS: In the development cohort, the Random Forest model showed a maximum receiver operating characteristic curve area of 0.96. In the external validation cohort, the Random Forest model surpasses 4 reported algorithms in predicting performance (accuracy 94.23%; sensitivity 97.10%; specificity 88.57%). In the prospective cohort, the Random Forest model showed good performance (accuracy 94.00%; sensitivity 85.71%; specificity 97.22%). CONCLUSION: Random Forest algorithm has improved the accuracy of distinguishing the origin of PVCs, which surpasses 4 previous standards, and would be used to identify the origin of PVCs before the interventional procedure.


Assuntos
Ablação por Cateter , Obstrução do Fluxo Ventricular Externo , Complexos Ventriculares Prematuros , Humanos , Complexos Ventriculares Prematuros/diagnóstico , Complexos Ventriculares Prematuros/cirurgia , Estudos Prospectivos , Ablação por Cateter/métodos , Eletrocardiografia/métodos
13.
J Hematol Oncol ; 15(1): 73, 2022 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-35659720

RESUMO

Despite tremendous success of molecular targeted therapy together with immunotherapy, only a small subset of patients can benefit from them. Chemotherapy remains the mainstay treatment for most of tumors including non-small cell lung cancer (NSCLC); however, non-selective adverse effects on healthy tissues and secondary resistance are the main obstacles. Meanwhile, the quiescent or dormant cancer stem-like cells (CSLCs) are resistant to antimitotic chemoradiotherapy. Complete remission can only be realized when both proliferative cancer cells and quiescent cancer stem cells are targeted. In the present research, we constructed a cooperatively combating conjugate (DTX-P7) composed of docetaxel (DTX) and a heptapeptide (P7), which specifically binds to cell surface Hsp90, and assessed the anti-tumor effects of DTX-P7 on non-small cell lung cancer. DTX-P7 preferentially suppressed tumor growth compared with DTX in vivo with a favorable distribution to tumor tissues and long circulation half-life. Furthermore, we revealed a distinctive mechanism whereby DTX-P7 induced unfolded protein response and eventually promoted apoptosis. More importantly, we found that DTX-P7 promoted cell cycle reentry of slow-proliferating CSLCs and subsequently killed them, exhibiting a "proliferate to kill" pattern. Collecitvely, by force of active targeting delivery of DTX via membrane-bound Hsp90, DTX-P7 induces unfolded protein response and subsequent apoptosis by degrading Hsp90, meanwhile awakens and kills the dormant cancer stem cells. Thus, DTX-P7 deserves further development as a promising anticancer therapeutic for treatment of various membrane-harboring Hsp90 cancer types.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Docetaxel/química , Docetaxel/farmacologia , Portadores de Fármacos/química , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Peptídeos/química , Peptídeos/farmacologia , Peptídeos/uso terapêutico
14.
Plant Reprod ; 35(3): 221-231, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35674836

RESUMO

It is widely known that an optimal nucleotide sequence context immediately upstream of the AUG start codon greatly improves the efficiency of translation initiation of mRNA in mammalian and plant somatic cells, which in turn increases protein levels. However, it is still unclear whether a similar regulatory mechanism is also present in highly differentiated cells. Here, we surveyed this issue in Arabidopsis thaliana sperm cells and found that the sequence context-mediated regulation of translation initiation in sperm cells is generally similar to that in somatic cells. A simple motif of four adenine nucleotides at positions - 1 to - 4 greatly improved the efficiency of translation initiation, and when the motif was present there, translation was even initiated at some non-AUG codons in sperm cells. However, unlike that in mammalian cells, a mainly effective nucleotide site to regulate the efficiency of translation initiation was not present at positions - 1 to - 4 in sperm cells. Meanwhile, different from somatic cells, sperm cells did not use eukaryotic translation initiation factor 1 to regulate the efficiency in a poor context consisting of the lowest frequency nucleotides. All these results contribute to our understanding of the cytoplasmic event of translation initiation in highly differentiated sperm cells.


Assuntos
Arabidopsis , Nucleotídeos , Animais , Arabidopsis/genética , Arabidopsis/metabolismo , Sequência de Bases , Códon de Iniciação/genética , Códon de Iniciação/metabolismo , Masculino , Mamíferos/genética , Mamíferos/metabolismo , Nucleotídeos/genética , Nucleotídeos/metabolismo , Biossíntese de Proteínas , Sementes/metabolismo , Espermatozoides/metabolismo
15.
Stem Cell Res ; 60: 102686, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35101669

RESUMO

Hypoglycemicagents have been shown to reduce the incidence of atrial fibrillation (AF) in patients with diabetes mellitus. Azoramide is a novel anti-diabetic agent which protects cells against endoplasmic reticulum (ER) stress; however, the cardioprotective effect of azoramide against AF is not clear. In this study, we aimed to investigate the protective effect of azoramide in human iPS-derived atrial myocytes (a-iCMs) against injury induced by high-frequency electrical stimulation. Human-induced pluripotent stem cells were differentiated into a-iCMs by treatment of retinoic acid. The tachypacing group was subjected to 7 Hz tachypacing for 48 h. Azoramide was preconditioned 2-hours before tachypacing. a-iCMs expressed atria-specific genes and the characteristics of the action potential were analogous to those of human atrial myocytes. Tachypacing induced disorder of intracellular calcium homeostasis, apoptosis, depressed ATP level, and severer myofilament dissolution. MetaboAnalysis revealed that tachypacing induced remarkable changes in metabolites involved in energy, amino acid, and glucose metabolism, whereas there was no significant effect on lipid metabolism. Azoramide pretreatment partly alleviated tachypacing-induced calcium dyshomeostasis, ATP consumption, and accelerated apoptosis, which was likely achieved by regulating the PERK/CHOP/CaMKII pathway. Azoramide protected atrial myocytes against injury induced by high-frequency electrical stimulation by regulating ER stress, which may inhibit cell apoptosis and calcium dyshomeostasis via the PERK/CHOP/CaMKII pathway.


Assuntos
Fibrilação Atrial , Células-Tronco Pluripotentes Induzidas , Trifosfato de Adenosina/metabolismo , Amidas , Fibrilação Atrial/genética , Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/farmacologia , Estresse do Retículo Endoplasmático , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Miócitos Cardíacos/metabolismo , Tiazóis
16.
Eur J Med Genet ; 65(3): 104429, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35063694

RESUMO

Primary fibrotic atrial cardiomyopathy (PF-ACM) is a novel type of cardiomyopathy characterized by primary atrial fibrosis with arrhythmogenicity and increased stroke risk without ventricular myocardium involvement. However, genetic analysis regarding PF-ACM and genotype-phenotype correlations is lacking. A cohort of PF-ACM patients was recruited and followed up. Whole-exome sequencing (WES) was applied, and genes were screened using a cardiovascular disease (CVD)-related gene panel. Echocardiography and cardiac magnetic resonance (CMR) were performed. The pathogenicity of the identified mutations was evaluated using in silico analysis. Thirty-three unrelated patients were referred for WES. Thirty-three rare variants of 19 CVD-related genes were identified in 21 patients, with 10 patients harboring more than one variation. TTN was the most frequent gene observed. Further analysis demonstrated that variations in sarcomeric (SV) or non-sarcomeric (NSV) genes were found in 16 and 10 patients, respectively. Patients carrying variants regardless of SV or NSV had larger left atrial dimensions determined by echo and larger left atrium areas determined by CMR. There was no discrepancy in disease severity between SV carriers and NSV carriers. Our genetic investigation into PF-ACM has identified several genetic culprits, providing further insight into its underlying pathophysiology and emphasizing a potential role for genetic testing for this condition.


Assuntos
Cardiomiopatias , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/genética , Fibrose , Estudos de Associação Genética , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/patologia , Humanos , Sequenciamento do Exoma
17.
Cardiology ; 147(1): 47-56, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34844237

RESUMO

INTRODUCTION: For those cardiac resynchronization therapy (CRT) candidates who experience left-ventricular (LV) lead placement failure or underwent concomitant cardiac surgeries, surgical placement of epicardial LV lead guided by electroanatomic mapping may be a promising alternative. METHODS: Electroanatomic mapping was used to guide positioning of the LV lead through a surgical approach. The LV lead was placed at the region with the latest local LV activation and normal voltage, away from the scar. RESULTS: From April 2010 to September 2018, 10 consecutive patients (3 female) underwent surgical epicardial LV lead implantation. Among them, 3 had other surgical indications simultaneously (including 1 CRT non-responder), and 7 had failed transvenous LV lead placement. After CRT, the QRS duration was shortened from 149.3 ± 20.4 ms to 125.1 ± 15.2 ms (p = 0.01). At 6 months, the LV ejection fraction was significantly improved and remained stable in the follow-up (FU) period thereafter (baseline vs. 6 months, 31.0 ± 8.3% vs. 42.2 ± 13.4%, p = 0.006). Other parameters, including the threshold and impedance of the LV lead, were also stable at a mean FU of 755 ± 406 days, and the NYHA functional classification decreased from 2.9 ± 0.7 to 1.8 ± 0.8 (p = 0.002). CONCLUSIONS: Placement of an epicardial LV lead guided by electroanatomic mapping could be used as an adjunctive strategy in patients who were unable or refractory to conventional CRT therapy. This approach could also be applied in patients who had other surgical indications at the same time.


Assuntos
Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca , Dispositivos de Terapia de Ressincronização Cardíaca , Feminino , Insuficiência Cardíaca/terapia , Ventrículos do Coração , Humanos , Resultado do Tratamento
18.
Neoplasma ; 69(6): 1386-1395, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36591801

RESUMO

Breast cancer (BC) is a prevalent neoplasm that occurs in women all over the world. Growth and differentiation factor 11 (GDF11) plays an essential role in cancer progression. This study focused on investigating the biological role and underlying mechanisms of GDF11 in BC. We detected the expression of GDF11 in 27 patients with BC and BC cell lines. Kaplan-Meier plotter was employed to analyze the relationship between GDF11 expression and overall survival (OS) of BC patients. The proliferative, migratory, invasive, and apoptotic abilities of T47D cells were examined. Correlation analysis of GDF11 with Smad ubiquitination regulatory factor 1 (SMURF1) was conducted. The association between GDF11 and the p53 pathway was analyzed by western blot and PFT-α (a p53 inhibitor)-mediated rescue assays. A brief analysis of the role of estrogen receptor alpha (ERα) signaling in BC progression was performed. The results showed that GDF11 was increased in BC tissues and cell lines, and the high expression of GDF11 was associated with the poor OS of BC patients. GDF11 knockdown inhibited the proliferation, migration, and invasion of T47D cells, but promoted cell apoptosis. Meanwhile, the GDF11 knockdown reduced the SMURF1 expression and invoked the p53 pathway activation. SMURF1 overexpression and PFT-α partially blocked the effects of GDF11 knockdown. In addition, GDF11 knockdown and SMURF1 silencing inhibited the activation of the ERα signaling pathway. In summary, GDF11 was involved in the progression of BC by regulating SMURF1-mediated p53 and ERα pathways, opening up a new way for BC treatment.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ubiquitina-Proteína Ligases/genética , Linhagem Celular Tumoral , Transdução de Sinais , Regulação Neoplásica da Expressão Gênica , Proliferação de Células , Proteínas Morfogenéticas Ósseas/metabolismo , Fatores de Diferenciação de Crescimento/genética , Fatores de Diferenciação de Crescimento/metabolismo
19.
Chinese Journal of School Health ; (12): 345-349, 2022.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-923102

RESUMO

Objective@#To determine the influencing factors of electronic screen time of urban preschoolers before and after the COVID-19 outbreak, so as to provide a scientific basis for the control of digital screen use and early prevention of myopia among preschoolers.@*Methods@#Using multi stage cluster random sampling method, a cross sectional survey of 8 244 kindergarten students in a district of Shanghai was implemented, through parent questionnaire collecting the time child spent on various electronic screens before and after the COVID-19 outbreak, estimated the weighting screen time, and emphatically analyzed the relationship between family electronic screen supervision behavior and preschoolers weighting screen time.@*Results@#The proportion of daily over use time on average of mobile phones, computers and TV/projection screens among the surveyed preschool children during COVID-19 was 30.52%, 51.40% and 56.82%, respectively. On school days before the epidemic, the proportion was 21.94%, 41.80% and 47.51% respectively. After controlling for primary covariates, parents frequent control of children s electronic screen use, parents guidance for electronic screen use were significantly associated with lower weighted screen refractive time ( OR =0.60-0.77, P < 0.05 ). The use of electronic screen when parents accompanied their children, the use of electronic screen time by parents but not strictly implemented were significantly associated with higher weighted screen refractive time and increased screen refractive time ( OR =1.18-1.80, P <0.05).@*Conclusion@#Urban preschoolers electronic screen time was high during and before COVID-19. In the control measures of preschool children s electronic screen time, attention should be paid to the management of electronic screen use within the family and parents role model.

20.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-920475

RESUMO

Objective@#The current situation and associated factors of primary and middle school students screen time and related eye hygiene in different periods before and after COVID-19 were investigated, so as to provide a scientific basis for taking targeted measures of preventing and controlling myopia among those students.@*Methods@#A total of 11 402 students were selected from 24 primary schools, 18 junior high schools and 16 high schools by multi stage stratified cluster sampling method. And a questionnaire survey was conducted among students and their parents to understand students screen time and screen hygiene behaviors and related factors in different periods before and after the outbreak of COVID-19.@*Results@#The rate of screen overuse was 7.26%, 9.12% and 35.30% during school days, weekends and home study, respectively. The overuse rate of mobile phones and tablets at home increases with the increase of school stage. Totally 16.30% of students use mobile phones for online learning. The screen overuse rate of those who have not been diagnosed with myopia was lower than that of those who have been diagnosed during home study( OR=0.77, P <0.05). The higher the parents educational level was, the lower the screen overuse rate of children during the weekends became( P <0.05). In any period, the high proportion of screens used in homework and poor home screen eye environment increased the risk of screen overuse and poor eye hygiene ( P <0.05). Parental good behavior was conducive to reducing the risk( OR= 0.65-0.97, P <0.05). When the family had regulation on the screen use time, the implementation of laxity would increase the risk of screen overuse ( OR=1.18-2.48, P <0.05).@*Conclusion@#The screen overuse rate of urban primary and middle school students during home study is high, and a certain proportion of students still use mobile phones for online learning. The proportion of screens used in homework, home screen eye environment and screen use management are related to screens overuse. More attention should be paid to those with myopia and low educational level of parents.

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