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1.
Nurs Open ; 2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34841737

RESUMO

AIM: To assess the effects of health locus of control-based education programme (HLCEP) on self-management, health locus of control and glycated haemoglobin (HbA1c) among type 2 diabetes mellitus (T2DM). DESIGN: Quasi-experimental study. METHODS: The study recruited 120 T2DM participants from May-September 2020. The control group received one-week in-hospital care and 12-week follow-up. The intervention group received additional HLCEP. The self-management and the health locus of control were measured by using the Summary of Diabetes Self-care Activities and the Multidimensional Health Locus of Control at baseline and the 4th and 12th week after discharge. The HbA1c was collected at baseline and the 12th week after discharge. The generalized estimating equation analysis was performed to assess the intervention effects. RESULTS: The intervention group has statistically significantly higher scores on the overall level of self-management, dietary management, foot care, medication management and internal health locus of control, while a lower HbA1c level than the control group.

2.
Cell Metab ; 33(10): 1943-1956.e2, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34478633

RESUMO

Metabolic dysfunction is becoming a predominant risk for the development of many comorbidities. Ischemic heart disease (IHD) still imposes the highest disease burden among all cardiovascular diseases worldwide. However, the contributions of metabolic risk factors to IHD over time have not been fully characterized. Here, we analyzed the global disease burden of IHD and 15 associated general risk factors from 1990 to 2019 by applying the methodology framework of the Global Burden of Disease Study. We found that the global death cases due to IHD increased steadily during that time frame, while the mortality rate gradually declined. Notably, metabolic risk factors have become the leading driver of IHD, which also largely contributed to the majority of IHD-related deaths shifting from developed countries to developing countries. These findings suggest an urgent need to implement effective measures to control metabolic risk factors to prevent further increases in IHD-related deaths.

3.
ACS Appl Mater Interfaces ; 13(28): 33218-33225, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34228914

RESUMO

Sn-based perovskite solar cells (PSCs) have received extensive attention for photovoltaic applications. Nevertheless, the low crystallization quality of the film due to rapid crystallization results in high trap density of states, which is one of the main reasons for poor performance of Sn-based PSC devices. In this work, we developed a strategy for the formation of FASnI3 perovskites by introducing the addition of formamidine acetate (FAAc). Benefiting from the iodide-coordinated cation (FA+) and crystallization-regulated anion (AC-), FAAc could achieve the high-quality films with suppressed defects. The champion power conversion efficiency (PCE) of FAAc-modified PSC devices reached 9.96%, reserving 82% of their initial PCE of the light aging test over 1500 h. We hope that our finding could provide implications on the high-performance and stable Sn-based PSCs.

4.
Cells Dev ; 165: 203664, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33993981

RESUMO

The Notch signaling pathway is highly conserved and regulates various fundamental development events. Activation of Notch signaling relies on production of the Notch intracellular domain (NICD), which assembles a transcription factor complex to turn on down-stream targets expression. The mastermind (mam) gene encodes an essential co-activator that permits NICD activity in the cell nucleus. During a somatic mosaic screen in Drosophila, an uncharacterized gene l(2)S9998 is identified as a positive regulator of the Notch signaling pathway. Genetic analysis demonstrates that l(2)S9998 functions at the level of transcriptional activation of Notch targets in the signal receiving cells. Whole genome sequencing reveals that l(2)S9998 is a novel allele of the mam gene, which is further confirmed by complementation tests. Along with three molecularly defined transposon insertions isolated from the screen, four mutants of mam are shown to modulate Notch signaling during fly wing development. Our analysis provides additional genetic resources for understanding mam function and Notch signaling regulation.

5.
Circ Res ; 128(11): 1747-1765, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34043417

RESUMO

Cardiac arrhythmias and the resulting sudden cardiac death are significant cardiovascular complications that continue to impose a heavy burden on patients and society. An emerging body of evidence indicates that nonalcoholic fatty liver disease (NAFLD) is closely associated with the risk of cardiac arrhythmias, independent of other conventional cardiometabolic comorbidities. Although most studies focus on the relationship between NAFLD and atrial fibrillation, associations with ventricular arrhythmias and cardiac conduction defects have also been reported. Mechanistic investigations suggest that a number of NAFLD-related pathophysiological alterations may potentially elicit structural, electrical, and autonomic remodeling in the heart, contributing to arrhythmogenic substrates in the heart. NAFLD is now the most common liver and metabolic disease in the world. However, the upsurge in the prevalence of NAFLD as an emerging risk factor for cardiac arrhythmias has received little attention. In this review, we summarize the clinical evidence and putative pathophysiological mechanisms for the emerging roles of NAFLD in cardiac arrhythmias, with the purpose of highlighting the notion that NAFLD may serve as an independent risk factor and a potential driving force in the development and progression of cardiac arrhythmias.

6.
Transl Oncol ; 14(6): 101075, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33773404

RESUMO

BACKGROUND: Cisplatin (DDP) remains the backbone of chemotherapy for non-small cell lung cancer (NSCLC), yet its clinical efficacy is limited by DDP resistance. We aim to investigate the role of the SET and MYND domain-containing protein 3 (SMYD3) in DDP resistance of NSCLC. METHODS: Expression pattern of SMYD3 was determined in NSCLC tissues using qRT-PCR, which also validated its correlation with NSCLC clinicopathological stages. Impacts of SMYD3 on DDP resistance were evaluated by knocking down SMYD3 in DDP-resistant cells and overexpressing it in DDP-sensitive cells, and assessed for several phenotypes: IC50 by MTT, long-term proliferation by colony formation, apoptosis and cell-cycle distribution by flow cytometry. The interaction between Ankyrin Repeat and KH Domain Containing 1 (ANKHD1) and SMYD3 was examined by co-immunoprecipitation and immunofluorescence. The transcriptional regulation of SMYD3 on cyclin-dependent kinase 2 (CDK2) promoter regions was confirmed using chromatin-immunoprecipitation. The in vivo experiments using DDP-resistant cells with altered SMYD3 and ANKHD1 expression were further performed to verify the SMYD3/ANKHD1 axis. RESULTS: Highly expressed SMYD3 was observed in NSCLC tissues or cells, acted as a sensitive indicator for NSCLC, correlated with higher TNM stages or resistant to DDP treatment, and shorter overall survival. The promotion of SMYD3 on DDP resistance requires co-regulator, ANKHD1. CDK2 was identified as a downstream effector. In vivo, SMYD3 knockdown inhibited the growth of DDP-resistant NSCLC cells, which was abolished by ANKHD1 overexpression. CONCLUSIONS: SMYD3 confers NSCLC cells chemoresistance to DDP in an ANKHD1-dependent manner, providing novel therapeutic targets to overcome DDP resistance in NSCLC .

7.
Ann Transl Med ; 9(1): 73, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33553366

RESUMO

Background: Neoadjuvant chemotherapy (NAC) and neoadjuvant chemoradiotherapy (NACR) are the standard treatments for esophageal squamous cell carcinoma (ESCC). However, the 5-year overall survival (OS) rate is still far from satisfactory. In recent years, immune checkpoint inhibitors (ICIs) have shown promising results in the treatment of ESCC. More than 20 phase II clinical trials have been launched to explore combinations of ICIs in the neoadjuvant setting for ESCC. Based on our phase II clinical trial, a two-arm phase III trial was launched in Henan Cancer Hospital. ICIs combined with NAC may usher in a new era and may benefit locally advanced, resectable ESCC patients. Methods: A two-arm phase III trial was launched in April 2020 in Henan Cancer Hospital. Patient recruitment will be completed within 18 months. The primary endpoint is event-free survival (EFS). The secondary endpoints include pathologic complete response (pCR), disease-free survival (DFS) rate, overall response rate (ORR), R0 resection rate, major pathologic response (MPR), adverse events (AEs), complication rate and quality of life (QOL). A biobank of pretreatment, resected tumor tissue and paired blood samples will be built for translational research in the future. Discussion: This RCT directly compares NAC with neoadjuvant toripalimab plus chemotherapy in terms of EFS for locally advanced ESCC. The results may usher in a new era of resectable ESCC treatment. Trial registration: NCT04280822 (https://www.clinicaltrials.gov/ct2/show/NCT04280822). Registered title: "A Phase III, Randomized Controlled Study of Neo-adjuvant Toripalimab (JS001) in Combination with Chemotherapy versus Neo-adjuvant Chemotherapy for Resectable Esophageal Squamous Cell Carcinoma". Version 1.0/Nov. 21, 2019.

8.
Cell Metab ; 33(2): 258-269.e3, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33421384

RESUMO

Corticosteroid therapy is now recommended as a treatment in patients with severe COVID-19. But one key question is how to objectively identify severely ill patients who may benefit from such therapy. Here, we assigned 12,862 COVID-19 cases from 21 hospitals in Hubei Province equally to a training and a validation cohort. We found that a neutrophil-to-lymphocyte ratio (NLR) > 6.11 at admission discriminated a higher risk for mortality. Importantly, however, corticosteroid treatment in such individuals was associated with a lower risk of 60-day all-cause mortality. Conversely, in individuals with an NLR ≤ 6.11 or with type 2 diabetes, corticosteroid treatment was not associated with reduced mortality, but rather increased risks of hyperglycemia and infections. These results show that in the studied cohort corticosteroid treatment is associated with beneficial outcomes in a subset of COVID-19 patients who are non-diabetic and with severe symptoms as defined by NLR.


Assuntos
Corticosteroides/uso terapêutico , COVID-19/tratamento farmacológico , Linfócitos/citologia , Neutrófilos/citologia , Corticosteroides/efeitos adversos , Área Sob a Curva , COVID-19/mortalidade , COVID-19/patologia , COVID-19/virologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Humanos , Hiperglicemia/complicações , Hiperglicemia/patologia , Tempo de Internação , Modelos de Riscos Proporcionais , Curva ROC , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do Tratamento
9.
Med (N Y) ; 2(1): 38-48.e2, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33043313

RESUMO

Background: The coronavirus disease 2019 (COVID-19) is a recently emerged respiratory infectious disease with kidney injury as a part of the clinical complications. However, the dynamic change of kidney function and its association with COVID-19 prognosis are largely unknown. Methods: In this multicenter retrospective cohort study, we analyzed clinical characteristics, medical history, laboratory tests, and treatment data of 12,413 COVID-19 patients. The patient cohort was stratified according to the severity of the outcome into three groups: non-severe, severe, and death. Findings: The prevalence of elevated blood urea nitrogen (BUN), elevated serum creatinine (Scr), and decreased blood uric acid (BUA) at admission was 6.29%, 5.22%, and 11.66%, respectively. The trajectories showed the elevation in BUN and Scr levels, as well as a reduction in BUA level for 28 days after admission in death cases. Increased all-cause mortality risk was associated with elevated baseline levels of BUN and Scr and decreased levels of BUA. Conclusions: The dynamic changes of the three kidney function markers were associated with different severity and poor prognosis of COVID-19 patients. BUN showed a close association with and high potential for predicting adverse outcomes in COVID-19 patients for severity stratification and triage. Funding: This study was supported by grants from the National Key R&D Program of China (2016YFF0101504), the National Science Foundation of China (81630011, 81970364, 81970070, 81970011, 81870171, and 81700356), the Major Research Plan of the National Natural Science Foundation of China (91639304), the Hubei Science and Technology Support Project (2019BFC582, 2018BEC473, and 2017BEC001), and the Medical Flight Plan of Wuhan University.

10.
Cell Cycle ; 20(1): 39-53, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33345719

RESUMO

Long non-coding RNA (lncRNA) X inactive specific transcript (XIST) has been identified as an oncogenic lncRNA in a series of human cancers, including esophageal squamous cell carcinoma (ESCC). In this study, we aimed to further explore the underlying mechanism of XIST on ESCC progression. qRT-PCR assay was used to determine the levels of XIST and miR-129-5p. Western blot analysis was performed to assess cyclin D1 (CCND1) expression. Bioinformatic analysis was performed using starBase v2.0 software. Dual-luciferase reporter and RNA immunoprecipitation assays were employed to confirm the interaction between XIST and miR-129-5p or miR-129-5p and CCND1. Cell cycle progression and apoptosis were measured by flow cytometric analysis, and cell migration and invasion were detected by transwell assay. Mouse studies were used to observe the effect of XIST silencing on tumor growth in vivo. Our results indicated that XIST was upregulated and miR-129-5p was downregulated in ESCC. XIST silencing or miR-129-5p overexpression repressed cell cycle progression, proliferation, migration, invasion, and promoted the apoptosis in ESCC cells. Moreover, XIST directly interacted with miR-129-5p and repressed miR-129-5p expression. MiR-129-5p mediated the regulatory effect of XIST on ESCC cell progression in vitro, and XIST promoted CCND1 expression by sponging miR-129-5p. Additionally, XIST silencing inhibited tumor growth in vivo. Our findings suggested that XIST silencing repressed the progression of ESCC at least partly through regulating the miR-129-5p/CCND1 axis. Targeting XIST might be a potential therapeutic strategy for ESCC treatment.

11.
World J Clin Cases ; 8(22): 5576-5588, 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33344548

RESUMO

BACKGROUND: Dipeptidyl peptidase-4 (DPP4) is commonly targeted to achieve glycemic control and has potent anti-inflammatory and immunoregulatory effects. Recent structural analyses indicated a potential tight interaction between DPP4 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), raising a promising hypothesis that DPP4 inhibitor (DPP4i) drugs might be an optimal strategy for treating coronavirus disease 2019 (COVID-19) among patients with diabetes. However, there has been no direct clinical evidence illuminating the associations between DPP4i use and COVID-19 outcomes. AIM: To illuminate the associations between DPP4i usage and the adverse outcomes of COVID-19. METHODS: We conducted a multicenter, retrospective analysis including 2563 patients with type 2 diabetes who were hospitalized due to COVID-19 at 16 hospitals in Hubei Province, China. After excluding ineligible individuals, 142 patients who received DPP4i drugs and 1115 patients who received non-DPP4i oral anti-diabetic drugs were included in the subsequent analysis. We performed a strict propensity score matching (PSM) analysis where age, sex, comorbidities, number of oral hypoglycemic agents, heart rate, blood pressure, pulse oxygen saturation (SpO2) < 95%, CT diagnosed bilateral lung lesions, laboratory indicators, and proportion of insulin usage were matched. Finally, 111 participants treated with DPP4i drugs were successfully matched to 333 non-DPP4i users. Then, a linear logistic model and mixed-effect Cox model were applied to analyze the associations between in-hospital DPP4i use and adverse outcomes of COVID-19. RESULTS: After rigorous matching and further adjustments for imbalanced variables in the linear logistic model and Cox adjusted model, we found that there was no significant association between in-hospital DPP4i use (DPP4i group) and 28-d all-cause mortality (adjusted hazard ratio = 0.44, 95%CI: 0.09-2.11, P = 0.31). Likewise, the incidences and risks of secondary outcomes, including septic shock, acute respiratory distress syndrome, or acute organ (kidney, liver, and cardiac) injuries, were also comparable between the DPP4i and non-DPP4i groups. The performance of DPP4i agents in achieving glucose control (e.g., the median level of fasting blood glucose and random blood glucose) and inflammatory regulation was approximately equivalent in the DPP4i and non-DPP4i groups. Furthermore, we did not observe substantial side effects such as uncontrolled glycemia or acidosis due to DPP4i application relative to the use of non-DPP4i agents in the study cohort. CONCLUSION: Our findings demonstrated that DPP4i use is not significantly associated with poor outcomes of COVID-19 or other adverse effects of anti-diabetic treatment. The data support the continuation of DPP4i agents for diabetes management in the setting of COVID-19.

12.
Appl Opt ; 59(24): 7284-7291, 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32902492

RESUMO

Retrieval of particle size distribution from bulk optical properties based on evolutionary algorithms is usually computationally expensive. In this paper, we report an efficient numerical approach to solving the inverse scattering problem by accelerating the calculation of bulk optical properties based on machine learning. With the assumption of spherical particles, the forward scattering by particles is first solved by Mie scattering theory and then approximated by machine learning. The particle swarm optimization algorithm is finally employed to optimize the particle size distribution parameters by minimizing the deviation between the target and simulated bulk optical properties. The accuracies of machine learning and particle swarm optimization are separately investigated. Meanwhile, both monomodal and bimodal size distributions are tested, considering the influences of random noise. Results show that machine learning is capable of accurately predicting the scattering efficiency for a specific size distribution in approximately 0.5 µs on a standalone computer. Therefore, the proposed method has the potential to serve as a powerful tool in real-time particle size measurement due to its advantages of simplicity and high efficiency.

13.
Cell Metab ; 32(4): 537-547.e3, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32861268

RESUMO

The safety and efficacy of anti-diabetic drugs are critical for maximizing the beneficial impacts of well-controlled blood glucose on the prognosis of individuals with COVID-19 and pre-existing type 2 diabetes (T2D). Metformin is the most commonly prescribed first-line medication for T2D, but its impact on the outcomes of individuals with COVID-19 and T2D remains to be clarified. Our current retrospective study in a cohort of 1,213 hospitalized individuals with COVID-19 and pre-existing T2D indicated that metformin use was significantly associated with a higher incidence of acidosis, particularly in cases with severe COVID-19, but not with 28-day COVID-19-related mortality. Furthermore, metformin use was significantly associated with reduced heart failure and inflammation. Our findings provide clinical evidence in support of continuing metformin treatment in individuals with COVID-19 and pre-existing T2D, but acidosis and kidney function should be carefully monitored in individuals with severe COVID-19.


Assuntos
Acidose/induzido quimicamente , Infecções por Coronavirus/complicações , Diabetes Mellitus Tipo 2/complicações , Metformina/efeitos adversos , Pneumonia Viral/complicações , Acidose Láctica/induzido quimicamente , Idoso , COVID-19 , China/epidemiologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/fisiopatologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Hospitalização , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/fisiopatologia , Estudos Retrospectivos
14.
BMC Infect Dis ; 20(1): 501, 2020 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-32652944

RESUMO

BACKGROUND: Tuberculosis (TB) still causes high economic burden on patients in China, especially for rural patients. Our study aims to explore the risk factors associated with the high costs for TB inpatients in rural China from the aspects of inpatients' socio-demographic and institutional attributes. METHODS: Generalized linear models were utilized to investigate the factors associated with TB inpatients' total costs and out-of-pocket (OOP) expenditures. Quantile regression (QR) models were applied to explore the effect of each factor across the different costs range and identify the risk factors of high costs. RESULTS: TB inpatients with long length of stay and who receive hospitalization services cross provincially, in tertiary and specialized hospitals were likely to face high total costs and OOP expenditures. QR models showed that high total costs occurred in Dingyuan and Funan Counties, but they were not accompanied by high OOP expenditures. CONCLUSIONS: Early diagnosis, standard treatment and control of drug-resistant TB are still awaiting for more efforts from the government. TB inpatients should obtain medical services from appropriate hospitals. The diagnosis and treatment process of TB should be standardized across all designated medical institutions. Furthermore, the reimbursement policy for migrant workers who suffered from TB should be ameliorated.


Assuntos
Tuberculose/economia , Adolescente , Adulto , Idoso , China , Feminino , Custos de Cuidados de Saúde , Gastos em Saúde , Humanos , Pacientes Internados , Tempo de Internação/economia , Masculino , Pessoa de Meia-Idade , Análise de Regressão , População Rural , Centros de Atenção Terciária/economia , Tuberculose/diagnóstico , Tuberculose/terapia , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/economia , Tuberculose Resistente a Múltiplos Medicamentos/terapia , Adulto Jovem
16.
Hepatology ; 72(2): 389-398, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32359177

RESUMO

BACKGROUND AND AIMS: Coronavirus disease 2019 (COVID-19) is a new infectious disease. To reveal the hepatic injury related to this disease and its clinical significance, we conducted a multicenter retrospective cohort study that included 5,771 adult patients with COVID-19 pneumonia in Hubei Province. APPROACH AND RESULTS: We reported the distributional and temporal patterns of liver injury indicators in these patients and determined their associated factors and death risk. Longitudinal liver function tests were retrospectively analyzed and correlated with the risk factors and death. Liver injury dynamic patterns differed in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBIL). AST elevated first, followed by ALT, in severe patients. ALP modestly increased during hospitalization and largely remained in the normal range. The fluctuation in TBIL levels was mild in the non-severe and the severe groups. AST abnormality was associated with the highest mortality risk compared with the other indicators of liver injury during hospitalization. Common factors associated with elevated liver injury indicators were lymphocyte count decrease, neutrophil count increase, and male gender. CONCLUSION: The dynamic patterns of liver injury indicators and their potential risk factors may provide an important explanation for the COVID-19-associated liver injury. Because elevated liver injury indicators, particularly AST, are strongly associated with the mortality risk, our study indicates that these parameters should be monitored during hospitalization.


Assuntos
Betacoronavirus , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/fisiopatologia , Fígado/fisiopatologia , Pneumonia Viral/mortalidade , Pneumonia Viral/fisiopatologia , Adulto , Idoso , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Biomarcadores , COVID-19 , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , SARS-CoV-2
17.
Cell Metab ; 31(6): 1068-1077.e3, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32369736

RESUMO

Type 2 diabetes (T2D) is a major comorbidity of COVID-19. However, the impact of blood glucose (BG) control on the degree of required medical interventions and on mortality in patients with COVID-19 and T2D remains uncertain. Thus, we performed a retrospective, multi-centered study of 7,337 cases of COVID-19 in Hubei Province, China, among which 952 had pre-existing T2D. We found that subjects with T2D required more medical interventions and had a significantly higher mortality (7.8% versus 2.7%; adjusted hazard ratio [HR], 1.49) and multiple organ injury than the non-diabetic individuals. Further, we found that well-controlled BG (glycemic variability within 3.9 to 10.0 mmol/L) was associated with markedly lower mortality compared to individuals with poorly controlled BG (upper limit of glycemic variability exceeding 10.0 mmol/L) (adjusted HR, 0.14) during hospitalization. These findings provide clinical evidence correlating improved glycemic control with better outcomes in patients with COVID-19 and pre-existing T2D.


Assuntos
Glicemia/análise , Infecções por Coronavirus/mortalidade , Diabetes Mellitus Tipo 2/sangue , Índice Glicêmico/fisiologia , Hiperglicemia/sangue , Pneumonia Viral/mortalidade , Idoso , Betacoronavirus/patogenicidade , COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Diabetes Mellitus Tipo 2/complicações , Suscetibilidade a Doenças/patologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Hiperglicemia/complicações , Hipoglicemiantes/uso terapêutico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/complicações , Insuficiência de Múltiplos Órgãos/mortalidade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Estudos Retrospectivos , SARS-CoV-2
18.
BMC Cancer ; 20(1): 303, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32293362

RESUMO

BACKGROUND: Neoadjuvant therapy plus oesophagectomy has been accepted as the standard treatment for patients with potentially curable locally advanced oesophageal cancer. No completed randomized controlled trial (RCT) has directly compared neoadjuvant chemotherapy and neoadjuvant chemoradiation in patients with oesophageal squamous cell carcinoma (ESCC). The aim of the current RCT is to investigate the impact of neoadjuvant chemotherapy plus surgery and neoadjuvant chemoradiotherapy plus surgery on overall survival for patients with resectable locally advanced ESCC. METHODS: This open label, single-centre, phase III RCT randomized patients (cT2-T4aN + M0 and cT3-4aN0M0) in a 1:1 fashion to receive either the CROSS regimen (paclitaxel 50 mg/m2; carboplatin (area under the curve = 2), q1w, 5 cycles; and concurrent radiotherapy, 41.4 Gy/23 F, over 5 weeks) or neoadjuvant chemotherapy (paclitaxel 175 mg/m2; and cisplatin 75 mg/m2, q21d, 2 cycles). Assuming a 12% 5-year overall survival difference in favour of the CROSS regimen, 80% power with a two-sided alpha level of 0.05 and a 5% dropout each year for an estimated 3 years enrolment, the power calculation requires 456 patients to be recruited (228 in each group). The primary endpoint is 5-year overall survival, with a minimum 5-year follow-up. The secondary endpoints include 5-year disease-free survival, toxicity, pathological complete response rate, postoperative complications, postoperative mortality and quality of life. A biobank of pre-treatment and resected tumour tissue will be built for translational research in the future. DISCUSSION: This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies. TRIAL REGISTRATION: NCT04138212, date of registration: October 24, 2019.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimiorradioterapia/métodos , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Esofagectomia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carboplatina/uso terapêutico , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Fracionamento da Dose de Radiação , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Masculino , Terapia Neoadjuvante , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Projetos de Pesquisa , Análise de Sobrevida , Resultado do Tratamento
19.
Cancer Med ; 9(12): 4371-4385, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32349184

RESUMO

There are three subtypes of undifferentiated human conventional osteosarcoma (HCOS): osteoblastic osteosarcoma (OOS), chondroblastic osteosarcoma (COS), and fibroblastic osteosarcoma (FOS). HCOS also exhibits heterogeneous pathological maldifferentiation in individual patients. Currently, the mechanism regulating HCOS differentiation remains unclear, and therapies are ineffective. Osteopontin (OPN) and osteocalcin (OCN) are markers of osteoblast maturation, and their expression is inhibited in HCOS. A previous study found that PLK2 inhibited TAp73 phosphorylation and consequent anti-OS function of TAp73 in OS cells with enriched TAp73. TAp73 was also reported to regulate bone cell calcification. Here, OOS was found to have higher TAp73 levels and PLK2 expression than those in COS, which is correlated with HCOS maldifferentiation according to Spearman analysis and affects patient prognosis according to Kaplan-Meier survival analysis. In the conventional OS cell-line Saos2 and in patient-derived xenograft OS (PDX-OS) cells, increased PLK2 expression owing to abundant TAp73 levels affected OPN and OCN content as measured by RT-PCR and Western blotting, and alizarin red staining showed that PLK2 affected calcium deposition in OS cells. In addition, PLK2 inhibition in PDX-OS cells prohibited clone formation, as indicated by a clonogenic assay, and sensitized OS cells to cisplatin (CDDP) (which consequently limited proliferation), as shown by the CCK-8 assay. In an established PDX animal model with abundant TAp73 levels, PLK2 inhibition or CDDP treatment prevented tumor growth and prolonged median survival. The combined therapeutic effect of PLK2 inhibition with CDDP treatment was better than that of either monotherapy. These results indicate that increased PLK2 levels due to enriched TAp73 affect osteogenic differentiation and maturation and OS prognosis. In conclusion, PLK2 is a potential target for differentiation therapy of OS with enriched TAp73.


Assuntos
Biomarcadores Tumorais/metabolismo , Diferenciação Celular , Regulação Neoplásica da Expressão Gênica , Osteogênese , Osteossarcoma/patologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteína Tumoral p73/metabolismo , Animais , Antineoplásicos/farmacologia , Apoptose , Biomarcadores Tumorais/genética , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Proliferação de Células , Cisplatino/farmacologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Osteossarcoma/tratamento farmacológico , Osteossarcoma/genética , Osteossarcoma/metabolismo , Prognóstico , Proteínas Serina-Treonina Quinases/genética , Células Tumorais Cultivadas , Proteína Tumoral p73/genética , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Curr Cancer Drug Targets ; 20(4): 288-294, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31702512

RESUMO

BACKGROUND: Recent studies have reported the vital roles of circular RNAs (circRNAs) in tumor progression. However, the function and expression profile of most circRNAs in osteosarcoma remain unclear. METHODS: We examined the expression of circEPSTI1, a circRNA, in 50 paired adjacent normal tissues and osteosarcoma tissues by qRT-PCR. Then, we further explored the function of circEPSTI1 in osteosarcoma progression in vitro and in vivo. For example, cell proliferation and migration were examined. Some experiments were performed to explore the regulatory function of circEPSTI1 in miRNA and to investigate the potential role of circEPSTI1 in osteosarcoma. RESULTS: We found that circEPSTI1 was significantly upregulated in osteosarcoma. Inhibition of circEPSTI1 suppressed the osteosarcoma cancer cell proliferation and migration in vitro. Dual luciferase reporter assay showed that circEPSTI1 and MCL1 (myeloid cell leukaemia 1) could bind to miR-892b and that MCL1 and circEPSTI1 were targets of miR-892b. CONCLUSION: Thus, the circEPSTI1-miR-892b-MCL1 axis affected osteosarcoma progression through the miRNA sponging mechanism. circEPSTI1 may serve as a target and biomarker for osteosarcoma treatment.


Assuntos
Neoplasias Ósseas/genética , Proteínas de Neoplasias/genética , Osteossarcoma/genética , RNA Circular/genética , Animais , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Progressão da Doença , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/biossíntese , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Osteossarcoma/metabolismo , Osteossarcoma/patologia , RNA Circular/biossíntese , RNA Circular/metabolismo
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