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1.
BMC Nephrol ; 25(1): 99, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493084

RESUMO

BACKGROUND: Patient experiences and survival outcomes can be influenced by the circumstances related to dialysis initiation and subsequent modality choices. This systematic review and meta-analysis aimed to explore the rate and reasons for peritoneal dialysis (PD) dropout following haemodialysis (HD) to PD switch. METHOD: This systematic review conducted searches in four databases, including Medline, PubMed, Embase, and Cochrane. The protocol was registered on PROSPERO (study ID: CRD42023405718). Outcomes included factors leading to the switch from HD to PD, the rate and reasons for PD dropout and mortality difference in two groups (PD first group versus HD to PD group). The Critical Appraisal Skills Programme (CASP) checklist and the GRADE tool were used to assess quality. RESULTS: 4971 papers were detected, and 13 studies were included. On meta-analysis, there was no statistically significant difference in PD dropout in the PD first group (OR: 0.81; 95%CI: 0.61, 1.09; I2 = 83%; P = 0.16), however, there was a statistically significant reduction in the rate of mortality (OR: 0.48; 95%CI: 0.25, 0.92; I2 = 73%; P = 0.03) compared to the HD to PD group. The primary reasons for HD to PD switch, included vascular access failure, patient preference, social issues, and cardiovascular disease. Causes for PD dropout differed between the two groups, but inadequate dialysis and peritonitis were the main reasons for PD dropout in both groups. CONCLUSION: Compared to the PD first group, a previous HD history may not impact PD dropout rates for patients, but it could impact mortality in the HD to PD group. The reasons for PD dropout differed between the two groups, with no statistical differences. Psychosocial reasons for PD dropout are valuable to further research. Additionally, establishing a consensus on the definition of PD dropout is crucial for future studies.


Assuntos
Doenças Cardiovasculares , Falência Renal Crônica , Diálise Peritoneal , Peritonite , Humanos , Diálise Renal/efeitos adversos , Diálise Peritoneal/efeitos adversos , Doenças Cardiovasculares/complicações , Peritonite/etiologia , Sistema de Registros , Falência Renal Crônica/complicações
2.
Head Neck ; 46(5): 1009-1019, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38441255

RESUMO

OBJECTIVE: To enhance the accuracy in predicting lymph node metastasis (LNM) preoperatively in patients with papillary thyroid microcarcinoma (PTMC), refining the "low-risk" classification for tailored treatment strategies. METHODS: This study involves the development and validation of a predictive model using a cohort of 1004 patients with PTMC undergoing thyroidectomy along with central neck dissection. The data was divided into a training cohort (n = 702) and a validation cohort (n = 302). Multivariate logistic regression identified independent LNM predictors in PTMC, leading to the construction of a predictive nomogram model. The model's performance was assessed through ROC analysis, calibration curve analysis, and decision curve analysis. RESULTS: Identified LNM predictors in PTMC included age, tumor maximum diameter, nodule-capsule distance, capsular contact length, bilateral suspicious lesions, absence of the lymphatic hilum, microcalcification, and sex. Especially, tumors larger than 7 mm, nodules closer to the capsule (less than 3 mm), and longer capsular contact lengths (more than 1 mm) showed higher LNM rates. The model exhibited AUCs of 0.733 and 0.771 in the training and validation cohorts respectively, alongside superior calibration and clinical utility. CONCLUSION: This study proposes and substantiates a preoperative predictive model for LNM in patients with PTMC, honing the precision of "low-risk" categorization. This model furnishes clinicians with an invaluable tool for individualized treatment approach, ensuring better management of patients who might be proposed observation or ablative options in the absence of such predictive information.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Carcinoma Papilar/cirurgia , Carcinoma Papilar/patologia , Esvaziamento Cervical , Tireoidectomia , Metástase Linfática/patologia , Estudos Retrospectivos , Linfonodos/patologia , Fatores de Risco
3.
Nat Commun ; 15(1): 1614, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38388525

RESUMO

While Ru owns superior catalytic activity toward hydrogen oxidation reaction and cost advantages, the catalyst deactivation under high anodic potential range severely limits its potential to replace the Pt benchmark catalyst. Unveiling the deactivation mechanism of Ru and correspondingly developing protection strategies remain a great challenge. Herein, we develop atomic Pt-functioned Ru nanoparticles with excellent anti-deactivation feature and meanwhile employ advanced operando characterization tools to probe the underlying roles of Pt in the anti-deactivation. Our studies reveal the introduced Pt single atoms effectively prevent Ru from oxidative passivation and consequently preserve the interfacial water network for the critical H* oxidative release during catalysis. Clearly understanding the deactivation nature of Ru and Pt-induced anti-deactivation under atomic levels could provide valuable insights for rationally designing stable Ru-based catalysts for hydrogen oxidation reaction and beyond.

4.
Front Endocrinol (Lausanne) ; 15: 1337322, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38362277

RESUMO

Background: Robotic assistance in thyroidectomy is a developing field that promises enhanced surgical precision and improved patient outcomes. This study investigates the impact of the da Vinci Surgical System on operative efficiency, learning curve, and postoperative outcomes in thyroid surgery. Methods: We conducted a retrospective cohort study of 104 patients who underwent robotic thyroidectomy between March 2018 and January 2022. We evaluated the learning curve using the Cumulative Sum (CUSUM) analysis and analyzed operative times, complication rates, and postoperative recovery metrics. Results: The cohort had a mean age of 36 years, predominantly female (68.3%). The average body mass index (BMI) was within the normal range. A significant reduction in operative times was observed as the series progressed, with no permanent hypoparathyroidism or recurrent laryngeal nerve injuries reported. The learning curve plateaued after the 37th case. Postoperative recovery was consistent, with no significant difference in hospital stay duration. Complications were minimal, with a noted decrease in transient vocal cord palsy as experience with the robotic system increased. Conclusion: Robotic thyroidectomy using the da Vinci system has demonstrated a significant improvement in operative efficiency without compromising safety. The learning curve is steep but manageable, and once overcome, it leads to improved surgical outcomes and high patient satisfaction. Further research with larger datasets and longer follow-up is necessary to establish the long-term benefits of robotic thyroidectomy.


Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Neoplasias da Glândula Tireoide , Humanos , Feminino , Adulto , Masculino , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/cirurgia
5.
Immunopharmacol Immunotoxicol ; 45(6): 692-700, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37358143

RESUMO

OBJECTIVE: Treatment with TNF-α inhibitors improve psoriasis with minimize/minor neutrophils infiltration and CXCL-1/8 expression in psoriatic lesions. However, the fine mechanism of TNF-α initiating psoriatic inflammation by tuning keratinocytes is unclear. Our previous research identified the deficiency of intracellular galectin-3 was sufficient to promote psoriasis inflammation characterized by neutrophil accumulation. This study aims to investigate whether TNF-α participated in psoriasis development through dysregulating galectin-3 expression. METHODS: mRNA levels were assessed through quantitative real-time PCR. Flow cytometry was used to detect cell cycle/apoptosis. Western blot was used to evaluate the activation of the NF-κB signaling pathway. HE staining and immunochemistry were used to detect epidermal thickness and MPO expression, respectively. Specific small interfering RNA (siRNA) was used to knock down hsa-miR-27a-3p while plasmids transfection was used to overexpress galectin-3. Further, the multiMiR R package was utilized to predict microRNA-target interaction. RESULTS AND DISCUSSION: We found that TNF-α stimulation altered cell proliferation and differentiation and promoted the production of psoriasis-related inflammatory mediators along with the inhibition of galectin-3 expression in keratinocytes. Supplement of galectin-3 could counteract the rise of CXCL-1/8 but not the other phenotypes of keratinocytes induced by TNF-α. Mechanistically, inhibition of the NF-κB signaling pathway could counteract the decrease of galectin-3 and the increase of hsa-miR-27a-3p expression whereas silence of hsa-miR-27a-3p could counteract the decrease of galectin-3 expression induced by TNF-α treatment in keratinocytes. Intradermal injection of murine anti-CXCL-2 antibody greatly alleviated imiquimod-induced psoriasis-like dermatitis. CONCLUSION: TNF-α initiates psoriatic inflammation by increasing CXCL-1/8 in keratinocytes mediated by the axis of NF-κB-hsa-miR-27a-3p-galectin-3 pathway.


Assuntos
Galectina 3 , Queratinócitos , MicroRNAs , Psoríase , Fator de Necrose Tumoral alfa , Fator de Necrose Tumoral alfa/farmacologia , Queratinócitos/metabolismo , Células HaCaT , Humanos , MicroRNAs/genética , Quimiocina CXCL1/metabolismo , Interleucina-8/metabolismo , Galectina 3/genética , Psoríase/genética , Psoríase/patologia , NF-kappa B/metabolismo , Transdução de Sinais , Feminino , Animais , Camundongos , Camundongos Endogâmicos C57BL
6.
Int Immunopharmacol ; 119: 110259, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37141670

RESUMO

Tumor-associated macrophages (TAMs), the major component of the tumor microenvironment (TME), play distinctly different roles in different tumors. High mobility group box 1 (HMGB1), a nonhistone protein in the nucleus, can perform functions during inflammation and cancers. However, the role of HMGB1 in the crosstalk between oral squamous cell carcinoma (OSCC) cells and TAMs remains unclear. Here, we established a coculture system of TAMs and OSCC cells to explore the bidirectional effect and potential mechanism of HMGB1 in OSCC cell-TAM interactions. Our results showed that HMGB1 was significantly upregulated in OSCC tissues and positively associated with tumor progression, immune cell infiltration and macrophage polarization. Then, knocking down HMGB1 in OSCC cells inhibited the recruitment and polarization of cocultured TAMs. Moreover, the knockdown of HMGB1 in macrophages not only suppressed polarization, but also inhibited cocultured OSCC cell proliferation, migration and invasion in vitro and in vivo. Mechanistically, macrophages secreted higher levels of HMGB1 than OSCC cells, and dampening endogenous HMGB1 reduced HMGB1 secretion. Both OSCC cell-generated and macrophage-endogenous HMGB1 may regulate TAM polarization by promoting receptor TLR4 expression and NF-κB/p65 activation and enhancing IL-10/TGF-ß expression. HMGB1 in OSCC cells may regulate macrophage recruitment via IL-6/STAT3. In addition, TAM-derived HMGB1 may affect aggressive phenotypes of cocultured OSCC cells by regulating the immunosuppressive microenvironment through the IL-6/STAT3/PD-L1 and IL-6/NF-κB/MMP-9 pathways. In conclusion, HMGB1 may regulate the crosstalk between OSCC cells and TAMs, including modulating macrophage polarization and attraction, enhancing cytokine secretion, and remodeling and creating an immunosuppressive TME to further affect OSCC progression.


Assuntos
Proteína HMGB1 , Neoplasias Bucais , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Linhagem Celular Tumoral , Proteína HMGB1/genética , Interleucina-6 , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , NF-kappa B/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Microambiente Tumoral , Macrófagos Associados a Tumor/metabolismo
7.
Materials (Basel) ; 15(23)2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36499894

RESUMO

In this study, three parameter optimization methods and two designs of experiments (DOE) were used for the optimization of three major design parameters ((bill diameter (D), billet length (L), and barrier wall design (BWD)) in crown forging to improve the formability of aluminum workpiece for shock absorbers. The first optimization method is the response surface method (RSM) combined with Box-Behnken's experimental design to establish fifteen (15) sets of parameter combinations for research. The second one is the main effects plot method (MEP). The third one is the multiobjective optimization method combined with Taguchi's experimental design method, which designed nine (9) parameter combinations and conducted research and analysis through grey relational analysis (GRA). Initially, a new type of forging die and billet in the controlled deformation zone (CDZ) was established by CAD (computer-aided design) modeling and the finite element method (FEM) for model simulation. Then, this investigation showed that the optimal parameter conditions obtained by these three optimization approaches (RSM, MEP, and multiobjective optimization) are consistent, with the same results. The best optimization parameters are the dimension of the billet ((D: 40 mm, the length of the billet (L): 205 mm, and the design of the barrier wall (BWD): 22 mm)). The results indicate that the optimization methods used in this research all have a high degree of accuracy. According to the research results of grey relational analysis (GRA), the size of the barrier wall design (BWD) in the controllable deformation zone (CDZ) has the greatest influence on the improvement of the preforming die, indicating that it is an important factor to increase the filling rate of aluminum crown forgings. At the end, the optimized parameters are verified by FEM simulation analysis and actual production validation as well as grain streamline distribution, processing map, and microstructure analysis on crown forgings. The novelty of this work is that it provides a novel preforming die through the mutual verification of different optimization methods to solve a typical problem such as material underfill.

8.
Polymers (Basel) ; 14(7)2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35406307

RESUMO

Poly-(butylene adipate-co-terephthalate) (PBAT) has become one of the most prevalent biodegradable plastic film materials owing to its good degradability, mechanical properties, and processability. However, the degradation time of this material was too fast and the functional period was short, which limited its application. Herein, three new tropolone-based UV absorbers (UVA-1C, UVA-4C and UVA-6C) were rationally designed and blended into PBAT. The PBAT/UVA films that formed were used against UV aging and prolonged the functional period of PBAT film. The three new absorbers were synthesized by bridging two tropolones using three different organic chains with different flexibility. Among them, the UVA-6C showed the strongest UV absorbance at around 238 nm and 320 nm. Consequently, the PBAT/UVA-6C film showed an extended validity period of 240 h in the Xenon lamp aging machine and a prolonged functional period of 8 d during the field application test when compared to pure PBAT. More importantly, a 7.8% increase in the maize yield was obtained under PBAT/UVA-6C film relative to pure PBAT film. Obviously, the novel prepared UVA-6C compound is a good candidate for UV absorption in PBAT, which makes PBAT/UVA-6C film more advantageous over pure PBAT in practical applications as biodegradable agricultural film.

9.
J Hand Surg Eur Vol ; 47(3): 314-320, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34472395

RESUMO

Non-traumatic upper extremity amputations are an increasing concern with the rising prevalence of diabetes mellitus. To ascertain the risk factors and mortality rates for these amputations, the demographic information, amputation history, comorbidities and clinical outcomes of 140 patients who underwent non-traumatic upper extremity amputations between 1 January 2004 and 31 October 2017 were studied. Correlations were assessed using Cochran-Armitage chi-squared tests, odds ratios and multivariate binomial logistic regression as appropriate. Diabetes mellitus, coronary artery disease, end-stage renal failure, peripheral arterial disease and prior lower extremity amputation were significant risk factors for multiple upper extremity amputations. One-year, 2-year and 5-year mortality rates were 12%, 15% and 38%, respectively, following first upper extremity amputation. The risk factors for upper extremity amputations correspond with those for lower extremity amputations, comprising mainly diabetes mellitus and its related comorbidities. The mortality rates for non-traumatic upper extremity amputations highlight their significant burden on patients.Level of evidence: III.


Assuntos
Amputação Cirúrgica , Falência Renal Crônica , Humanos , Estudos Retrospectivos , Fatores de Risco , Extremidade Superior/cirurgia
10.
Nephron ; 145(3): 256-264, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33780937

RESUMO

INTRODUCTION: Acute kidney injury (AKI) in coronavirus infection disease (COVID-19) is associated with disease severity. We aimed to evaluate risk factors associated with AKI beyond COVID-19 severity. METHODS: A retrospective observational study of COVID-19 patients admitted to a tertiary hospital in Singapore. Logistic regression was used to evaluate associations between risk factors and AKI (based on Kidney Disease Improving Global Outcomes criteria). Dominance analysis was performed to evaluate the relative importance of individual factors. RESULTS: Seven hundred seven patients were included. Median age was 46 years (interquartile range [IQR]: 29-57) and 57% were male with few comorbidities (93%, Charlson Comorbidity Index [CCI] <1). AKI occurred in 57 patients (8.1%); 39 were in AKI stage 1 (68%), 9 in stage 2 (16%), and 9 in stage 3 (16%). Older age (adjusted odds ratio [aOR] 1.04; 95% confidence interval [CI]: 1.01-1.07), baseline use of angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) (aOR 2.86; 95% CI: 1.20-6.83), exposure to vancomycin (aOR 5.84; 95% CI: 2.10-16.19), use of nonsteroidal anti-inflammatory drugs (NSAIDs) (aOR 3.04; 95% CI: 1.15-8.05), and severe COVID-19 with hypoxia (aOR 13.94; 95% CI: 6.07-31.98) were associated with AKI in the multivariable logistic regression model. The 3 highest ranked predictors were severe COVID-19 with hypoxia, vancomycin exposure, and age, accounting for 79.6% of the predicted variance (41.6, 23.1, and 14.9%, respectively) on dominance analysis. CONCLUSION: Severe COVID-19 is independently associated with increased risk of AKI beyond premorbid conditions and age. Appropriate avoidance of vancomycin and NSAIDs are potentially modifiable means to prevent AKI in patients with COVID-19.


Assuntos
Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , COVID-19/complicações , COVID-19/epidemiologia , Adulto , Fatores Etários , Idoso , Antibacterianos/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Estudos de Coortes , Comorbidade , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Humanos , Hipóxia/epidemiologia , Hipóxia/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Vancomicina/efeitos adversos
11.
Exp Cell Res ; 396(2): 112290, 2020 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-32956704

RESUMO

PURPOSE: Recent findings have shown that circRNA dysregulation was involved in the development of many types of cancer. However, our knowledge of circRNA in oral squamous cell carcinoma (OSCC) remains elusive. METHODS: Here, we explored whether ciRS-7 could function as a ceRNA in promoting metastasis of OSCC via regulating miR-7 activity. The expression levels of ciRS-7 and miR-7 were examined in clinical samples and cell lines by qRT-PCR, and the effects of ectopic expression of ciRS-7 and miR-7 on cell proliferation, migration and invasion were assessed in vitro and in vivo. The effects of ciRS-7 on miR-7 activity were investigated by means of luciferase reporter assay, qRT-PCR and Western blot. In addition, the effects of miR-7 mediated ciRS-7 on the levels of MAPK/AKT signaling proteins were evaluated by Western blot. RESULTS: We found that ciRS-7 was highly expressed in OSCC tissues and cell lines compared with normal counterparts. Ectopic expression of ciRS-7 significantly promoted OSCC cell proliferation, migration and invasion through in vitro and in vivo. Based on bioinformatics analysis, qRT-PCR, Western blot and luciferase reporter assays, we determined that ciRS-7 functioned as a sponge for miR-7, resulting in attenuation of miR-7 targets RAF-1 and PIK3CD, which are core components of the MAPK/AKT signaling pathways. Moreover, miR-7 correlated with perineural and lymphovascular invasion in OSCC patients. Further experiments demonstrated that ciRS-7 overexpression could attenuate the anti-tumor effects of miR-7 on OSCC cells. CONCLUSIONS: Our results suggested that ciRS-7 can interact directly with miR-7, resulting in upregulation of RAF-1/PIK3CD expression and enhancing metastatic progression of OSCC.


Assuntos
Carcinoma de Células Escamosas/genética , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Progressão da Doença , Sistema de Sinalização das MAP Quinases , Neoplasias Bucais/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-raf/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Sequência de Bases , Carcinogênese/patologia , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Bucais/patologia , Invasividade Neoplásica , Metástase Neoplásica , RNA Longo não Codificante/genética , Regulação para Cima/genética
12.
SLAS Technol ; 25(6): 522-544, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32808850

RESUMO

In 2019, a novel coronavirus (SARS-CoV-2) was found to cause a highly contagious disease characterized by pneumonia. The disease (COVID-19) quickly spread around the globe, escalating to a global pandemic. In this review, we discuss the virological, immunological, and imaging approaches harnessed for COVID-19 diagnosis and research. COVID-19 shares many clinical characteristics with other respiratory illnesses.Accurate and early detection of the infection is pivotal to controlling the outbreak, as this enables case identification, isolation, and contact tracing. We summarize the available literature on current laboratory and point-of-care diagnostics, highlight their strengths and limitations, and describe the emerging diagnostic approaches on the horizon.We also discuss the various research techniques that are being used to evaluate host immunity in laboratory-confirmed patients. Additionally, pathological imaging of tissue samples from affected patients has a critical role in guiding investigations on this disease. Conventional techniques, such as immunohistochemistry and immunofluorescence, have been frequently used to characterize the immune microenvironment in COVID-19. We also outline the emerging imaging techniques, such as the RNAscope, which might also aid in our understanding of the significance of COVID-19-specific biomarkers, such as the angiotensin-converting enzyme 2 (ACE2) cellular receptor.Overall, great progress has been made in COVID-19 research in a short period. Extensive, global collation of our current knowledge of SARS-CoV-2 will provide insights into novel treatment modalities, such as monoclonal antibodies, and support the development of a SARS-CoV-2 vaccine.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/imunologia , COVID-19/virologia , SARS-CoV-2/fisiologia , Linfócitos T/imunologia , Enzima de Conversão de Angiotensina 2/metabolismo , Antígenos Virais/imunologia , Biomarcadores/metabolismo , COVID-19/diagnóstico , Diagnóstico por Imagem , Humanos , Testes Imediatos
13.
Ther Adv Neurol Disord ; 12: 1756286419864830, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31384308

RESUMO

BACKGROUND: It remains debatable whether statin increases the risk of intracerebral hemorrhage (ICH) in poststroke patients. METHODS: We systematically searched PubMed, EMBASE, and CENTRAL for randomized controlled trials. Trial sequential analysis (TSA) was conducted to assess the reliability and conclusiveness of the available evidence in the meta-analysis. To evaluate the overall effectiveness, the net composite endpoints were derived by totaling ischemic stroke, hemorrhagic stroke, transient ischemic attack (TIA), myocardial infarction, and cardiovascular mortality. RESULTS: A total of 17 trials with 11,576 subjects with previous ischemic stroke, TIA, or ICH were included, in which statin therapy increased the risk of hemorrhagic stroke (risk ratio [RR], 1.42; 95% confidence interval [CI], 1.07-1.87), but reduced the risk of ischemic stroke (RR, 0.85; 95% CI, 0.75-0.95). For the net composite endpoints, statin therapy was associated with a 17% risk reduction (95% CI, 12-21%; number needed to treat = 6). With a control event rate 2% and RR increase 40%, the TSA suggested a conclusive signal of an increased risk of hemorrhagic stroke in stroke survivors taking statin. However, with the sensitivity analysis by changing assumptions, the conclusions about hemorrhagic stroke risk were less robust. CONCLUSIONS: Statin therapy in poststroke patients increased the risk of hemorrhagic stroke but effectively reduced ischemic stroke risk. Weighing the benefits and potential harms, statin has an overall beneficial effect in patients with previous stroke or TIA. However, more studies are required to investigate the conclusiveness of the increased hemorrhagic stroke risk revealed in our study.

14.
Breast Cancer Res Treat ; 178(2): 295-305, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31410680

RESUMO

PURPOSE: We used multiplex immunofluorescence (mIF) to determine whether mitotic rate represents an independent prognostic marker in triple-negative breast cancer (TNBC). Secondary aims were to confirm the prognostic significance of immune cells in TNBC, and to investigate the relationship between immune cells and proliferating tumour cells. METHODS: A retrospective Asian cohort of 298 patients with TNBC diagnosed from 2003 to 2015 at the Singapore General Hospital was used in the present study. Formalin-fixed, paraffin-embedded breast cancer samples were analysed on tissue microarrays using mIF, which combined phospho-histone H3 (pHH3) expression with cytokeratin (CK) and leukocyte common antigen (CD45) expression to identify tumour and immune cells, respectively. RESULTS: Multivariate analysis showed that a high pHH3 index was associated with significantly improved overall survival (OS; p = 0.004), but this was not significantly associated with disease-free survival (DFS; p = 0.22). Similarly, multivariate analysis also revealed that a pHH3 positive count of > 1 cell per high-power field in the malignant epithelial compartment was an independent favourable prognostic marker for OS (p = 0.033) but not for DFS (p = 0.250). Furthermore, a high CD45 index was an independent favourable prognostic marker for DFS (p = 0.018), and there was a significant positive correlation between CD45 and pHH3 index (Spearman rank correlation coefficient, 0.250; p < 0.001). CONCLUSIONS: Mitotic rates as determined by pHH3 expression in epithelial cells are significantly associated with improved survival in TNBC. mIF analysis of pHH3 in combination with CK and CD45 could help clinicians in prognosticating patients with TNBC.


Assuntos
Histonas/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Biomarcadores , Feminino , Imunofluorescência , Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Antígenos Comuns de Leucócito , Fosforilação , Prognóstico , Reprodutibilidade dos Testes , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologia
15.
Virchows Arch ; 475(6): 709-725, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31407032

RESUMO

The proliferation marker Ki-67 is frequently used to assess aggressiveness in the pathological evaluation of cancer, but its role remains uncertain in triple-negative breast cancer (TNBC). We aimed to quantify and localize Ki-67 expression in both epithelial and immune compartments in TNBC and investigate its association with clinicopathological parameters and survival outcomes. A total of 406 TNBC cases diagnosed between 2003 and 2015 at Singapore General Hospital were recruited. Using state-of-the-art, 7-colour multiplex immunofluorescence (mIF) tissue microarrays (TMAs) were stained to assess the abundance, density and spatial distribution of Ki-67-positive tumour cells and immune cells co-decorated with cytokeratin (CK) and leukocyte common antigen (CD45) respectively. Furthermore, MKI67 mRNA profiles were analysed using NanoString technology. In multivariate analysis adjusted for tumour size, histologic grade, age at diagnosis, and lymph node stage, a high Ki-67 labelling index (LI) > 0.3% was associated with improved disease-free survival (DFS; HR = 0.727; p = 0.027). High Ki-67-positive immune cell count per TMA was a favourable prognostic marker for both DFS (HR = 0.379; p = 0.00153) and overall survival (OS; HR = 0.473; p = 0.0482). The combination of high Ki-67 LI and high MKI67 expression was associated with improved DFS (HR = 0.239; p = 0.00639) and OS (HR = 0.213; p = 0.034). This study is among the first to highlight that Ki-67 is associated with favourable prognosis in an adjuvant setting in TNBC, and the mIF-based evaluation of Ki-67 expression on both tumour and immune cells represents a novel prognostic approach.


Assuntos
Antígeno Ki-67/genética , Linfonodos/patologia , Receptores de Progesterona/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Ásia , Biomarcadores Tumorais/genética , Intervalo Livre de Doença , Feminino , Humanos , Queratinas/genética , Pessoa de Meia-Idade , Prognóstico , Neoplasias de Mama Triplo Negativas/diagnóstico
16.
Phytopathology ; 109(10): 1689-1697, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31188071

RESUMO

Clubroot caused by Plasmodiophora brassicaeis one of the most important diseases in cruciferous crops. The recognition of P. brassicae by host plants is thought to occur at the primary infection stage, but the underlying mechanism remains unclear. Secretory proteins as effector candidates play critical roles in the recognition of pathogens and the interactions between pathogens and hosts. In this study, 33 P. brassicae secretory proteins expressed during primary infection were identified through transcriptome, secretory protein prediction, and yeast signal sequence trap analyses. Furthermore, the proteins that could suppress or induce cell death were screened through an Agrobacterium-mediated plant virus transient expression system and a protoplast transient expression system. Two secretory proteins, PBCN_002550 and PBCN_005499, were found to be capable of inducing cell death associated with H2O2 accumulation and electrolyte leakage in Nicotiana benthamiana. Moreover, PBCN_002550 could also induce cell death in Chinese cabbage. In addition, 24 of the remaining 31 tested secretory proteins could suppress mouse Bcl-2-associated X protein-induced cell death, and 28 proteins could suppress PBCN_002550-induced cell death.


Assuntos
Brassica , Nicotiana , Plasmodioforídeos , Animais , Brassica/parasitologia , Morte Celular , Linhagem Celular , Peróxido de Hidrogênio/metabolismo , Camundongos , Doenças das Plantas/parasitologia , Proteínas de Protozoários/metabolismo , Nicotiana/parasitologia
17.
Oncotarget ; 8(35): 58292-58303, 2017 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-28938556

RESUMO

The impact of pharmacogenetics on predicting survival in diffuse large B-cell lymphoma (DLBCL) remains unclear. We tested 337 DLBCL patients treated with rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for 9 single nucleotide polymorphisms from 6 genes (CD20, FCGR2A, NAD(P)H, ABCC2, ABCG2 and CYP3A5). Patients who carried the NCF4 rs1883112 GG genotype showed significantly shorter progression-free survival (PFS) (P = 0.023) and event-free survival (EFS) (P < 0.001) comparing with A allele. A significantly shortened PFS (P = 0.013) and EFS (P = 0.002) was also observed in the patients with ABCG2 rs2231137 GG genotype. Furthermore, the elder (> 60 years old) or male patients with ABCG2 rs2231137 GG genotype had poorer PFS and EFS than A allele. Moreover, CD20 rs2070770 CC and RAC2 rs13058338 AT genotypes were independent predictors of chemotherapy-induced toxicity. Cox proportional hazards analyses demonstrated that the GG genotype of ABCG2 rs2231137 and NCF4 rs1883112 were risk factors in DLBCL patients. In conclusion, the identified polymorphisms provide guide for the identification of DLBCL patients who are likely to benefit from chemotherapy.

18.
J Proteome Res ; 13(12): 5879-87, 2014 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-25327737

RESUMO

Quantitative metabolomics (qMetabolomics) is a powerful tool for understanding the intricate metabolic processes involved in plant abiotic stress responses. qMetabolomics is hindered by the limited coverage and high cost of isotopically labeled standards. In this study, we first selected 271 metabolites which might play important roles in abiotic stress responses as the targets and established a comprehensive LC-MS/MS based qMetabolomic method. We then developed a novel metabolic labeling method using E. coli-Saccharomyces cerevisiae two-step cultivation for the production of uniformly (13)C-labeled metabolites as internal standards. Finally, we applied the developed qMetabolomic method to investigate the influence of Pb stress on maize root metabolism. The absolute concentration of 226 metabolites in maize roots was accurately quantified in a single run within 30 min. Our study also revealed that glycolysis, purine, pyrimidine, and phospholipids were the main metabolic pathways in maize roots involved in Pb stress response. To our knowledge, this is the most comprehensive qMetabolomic method for plant metabolomics thus far. We developed a simple and inexpensive metabolic labeling method which dramatically expanded the availability of uniformly (13)C labeled metabolites. Our findings also provided new insights of maize metabolic responses to Pb stress.


Assuntos
Metaboloma , Raízes de Plantas/metabolismo , Zea mays/metabolismo , Chumbo/farmacologia , Metabolômica , Raízes de Plantas/efeitos dos fármacos , Estresse Fisiológico , Espectrometria de Massas em Tandem , Zea mays/efeitos dos fármacos
19.
Am J Mens Health ; 8(2): 159-66, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24027205

RESUMO

Male osteoporosis is underappreciated. Little is known about men's knowledge of osteoporosis and how much men are at risk. This study surveyed men's knowledge of osteoporosis and their risk factors with reference to women in the primary care setting in Macau, China. A convenience sample of 302 men and 635 women aged 18 to 90 years completed questionnaires comprising the Osteoporosis Knowledge Assessment Tool and the One-Minute Osteoporosis Risk Test. Their risks of osteoporosis were assessed with the Osteoporosis Self-Assessment Screening Test. Men and women, who were aged 55 years or below, had similarly limited knowledge of osteoporosis. People aged above 55 years had significantly less knowledge; men had less knowledge than women only in this age-group. If questions specific to women or menopause were excluded, men had similar knowledge as women. A higher proportion of men than women had risk factors as more men consumed alcohol or smoked tobacco. Similar proportions of men and women reported a loss of 1 inch in body height after age 40. After age 55, 29.2% men were at medium to high risk of osteoporosis. This study concludes that health education and primary prevention of osteoporosis should be promoted to men starting in middle-age.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Osteoporose , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Sexuais , Inquéritos e Questionários , Adulto Jovem
20.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 33(4): 452-5, 2013 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-23841260

RESUMO

OBJECTIVE: To explore the features of DNA damage in nasopharyngeal carcinoma (NPC) patients of normal constitution and abnormal constitution and in high-risk population of NPC. METHODS: Using single cell gel electrophoresis technique, the DNA damage of peripheral blood lymphocytes was detected in 28 healthy subjects, 27 in high-risk population of NPC, and 13 NPC patients at their first visits. The DNA damage was detected in the populations of normal constitution and of abnormal constitution. The tail length, the tail moment, and the tail DNA% were taken as the indices of DNA damage. RESULTS: The tail length was (35.77 +/- 4.22) microm, the tail moment was (8.10 +/- 1.63) microm, and the tail DNA% was 57.48% +/- 4.63% in NPC patients. They were (15.25 +/- 4.15) microm, (5.01 +/- 1.92) microm, and 31.99% +/- 4. 11% in high-risk population of NPC. They were (14.31 +/- 3.64) microm, (4. 37 +/- 1.80) microm, and 29. 89% +/- 3. 15% in healthy subjects. There was statistical difference in the three indices among the three populations (P <0.05). In all the three populations, more DNA damage existed in those of abnormal constitution than in those of normal constitution (P <0.05). CONCLUSIONS: Obvious instability of genetic materials exists in NPC patients, manifested as severe DNA damage of lymphocytes. In all the three populations, more DNA damage existed in those of abnormal constitution than in those of normal constitution.


Assuntos
Constituição Corporal , Dano ao DNA , Medicina Tradicional Chinesa , Neoplasias Nasofaríngeas/genética , Adolescente , Adulto , Idoso , Carcinoma , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/epidemiologia , Adulto Jovem
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