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2.
Life Sci ; 268: 119009, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33412210

RESUMO

AIMS: Salivary gland dysfunction is a common complication of diabetes mellitus (DM). Long non-coding RNA (lncRNA) is evidenced to involve in the functional regulation of salivary gland, however, its role in DM-impaired gland is unknown. Therefore, this study aimed to investigate the expression profiles and functional networks of lncRNA in the parotid glands (PGs) of DM mice. MAIN METHODS: Microarray was used to detect lncRNA and messenger RNA (mRNA) expression profiles in the PGs from db/db and db/m mice. Eleven differently expressed (DE) lncRNAs validated by qRT-PCR were selected for coding-non-coding gene co-expression (CNC) and competing endogenous RNA (ceRNA) network analysis, as well as the following Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Pearson's coefficient correlation analysis was used to analyze the correlations between DE lncRNAs expression and DM pathology. KEY FINDINGS: By using a 2-fold change and P < 0.05 as the cutoff criteria, 1650 DE lncRNAs (758 upregulated and 892 downregulated) and 1073 mRNAs (563 upregulated and 510 downregulated) were identified in the PGs of db/db mice compared to db/m mice. GO and KEGG analysis of DE mRNA suggested that activated inflammation response and downregulated ion transport might count for the dysfunction of diabetic PG. CNC and ceRNA networks analysis of 11 DE lncRNAs showed that the inflammation process and its related signaling pathways including advanced glycation end product (AGE)-receptor for AGE (RAGE) signaling pathway in diabetic complications, cytokine-cytokine receptor interaction, chemokine signaling pathway, apoptosis, and cell adhesion molecules were significantly enriched. The alterations of lncRNAs were closely correlated with higher blood glucose and serum insulin levels in mice. SIGNIFICANCE: We identified multiple lncRNAs/mRNAs and several signaling pathways that may involve in the pathogenesis of diabetic salivary injury, providing new insight into potential target of diabetic hyposalivation.

3.
Heart Fail Rev ; 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33443725

RESUMO

Noninvasive positive-pressure ventilation (NPPV) is recognized as an effective adjuvant therapy for sleep-disordered breathing (SDB) in heart failure patients with reduced ejection fraction (HFrEF + SDB). In recent years, some studies have found that adaptive servo-ventilation (ASV) has a negative impact on survival, especially among patients with central sleep apnea (CSA), the use of which is controversial. This study aims to explore the effects of NPPV on cardiac function and survival in patients with sleep-disordered breathing and chronic congestive heart failure. This meta-analysis was based on literature searches of publications published before August 31, 2019, in the PubMed, EMBASE, Cochrane Library, and Web of Science databases. A total of 88 independent studies were summarized and compared, comprising a sampling of 19,259 subjects. Compared with the nontreatment group, treatment with ASV had no effect on all-cause mortality in patients with HFrEF + CSA (hazard ratio (HR) = 1.13 [0.84, 1.51]). Short-term treatment with ASV, e.g., 3-6 months, was significantly beneficial regarding event-free survival in patients with HFrEF + CSA (HR = 0.13 [0.04, 0.45]). Periodic short-term (e.g., 3-6 months) positive-pressure ventilation can significantly improve cardiac function, which is beneficial for the survival of patients with HFrEF + CSA. Attention should be paid to the length and period of treatment, as prolonged treatment may have negative effects.

4.
J Cell Physiol ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33400820

RESUMO

C1q/tumor necrosis factor-related protein-6 (CTRP6) is a newly identified adipokine involved in diverse biological processes. However, its role in salivary glands remains unknown. Here, we demonstrated that CTRP6 was mainly distributed in the nuclei, apicolateral membranes, and cytoplasm of human submandibular glands (SMGs), serous cells of parotid glands, and ducts and apicolateral membranes of serous cells in rats and mice. CTRP6 inhibited the apoptosis rate and reversed the increased levels of cleaved caspase 3, caspase 8, caspase 9, and cytochrome C and the decreased Bcl-2 expression induced by tumor necrosis factor (TNF)-α in both SMG-C6 cells and cultured human SMG tissues. Microarray analysis identified 43 differentially expressed microRNAs (miRNAs) in the SMGs of nonobese diabetic mice. miR-34a-5p was selected due to its upregulation by TNF-α, which was abolished by CTRP6. The miR-34a-5p inhibitor promoted whereas the miR-34a-5p mimic suppressed the effects of CTRP6 on TNF-α-induced apoptosis. CTRP6 increased AMP-activated protein kinase (AMPK) phosphorylation and reversed TNF-α-induced SIRT1 downregulation in salivary cells. AraA, an AMPK inhibitor, reversed the effects of CTRP6 on TNF-α-induced alterations in the levels of SIRT1, miR-34a-5p, Bcl-2, and cleaved caspase 3 in vitro and ex vivo, whereas activating AMPK by AICAR reversed the decrease in SIRT1 expression and increase in miR-34a-5p expression induced by TNF-α. Inhibition of SIRT1 by EX527 suppressed the effects of CTRP6 on TNF-α-induced changes in miR-34a-5p and apoptosis-related proteins. Our findings indicate that salivary glands are novel sites for CTRP6 synthesis and secretion. CTRP6 protects acinar cells against TNF-α-induced apoptosis via AMPK/SIRT1-modulated miR-34a-5p expression.

5.
Genomics ; 113(1 Pt 1): 57-65, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33227410

RESUMO

The aim of this study was to elucidate the roles played by circular RNAs (circRNAs) in the mechanism underlying submandibular gland (SMG) dysfunction in hypertension. We employed RNA-seq to analyze the circRNA and mRNA expression profiles of SMGs. Seventy-five differentially expressed (DE) circRNAs and 691 DE mRNAs were determined to be significantly altered in spontaneously hypertensive rats. Altered mRNAs were primarily related to the immune system and immune response. Eight circRNAs were selected for further analysis. Cell adhesion molecules were determined to be the most strongly enriched pathway through analysis of DE mRNAs, the coding noncoding gene co-expression (CNC) network and the competitive endogenous RNA (ceRNA) network. The salivary secretion pathway was observed to be notably enriched through analysis of the ceRNA network. These results suggest that the crosstalk among circRNAs may play a crucial role in the development of SMG dysfunction in hypertension.

6.
Eur Heart J ; 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33211823

RESUMO

AIMS: The aim of this study was to clarify the effect of ß-blockers (BBs) on respiratory function and survival in patients with chronic obstructive pulmonary disease with cardiovascular disease (CVD), as well as the difference between the effects of cardioselective and noncardioselective BBs. METHODS AND RESULTS: We searched for relevant literature in four electronic databases, namely, PubMed, EMBASE, Cochrane Library, and Web of Science, and compared the differences in various survival indicators between patients with chronic obstructive pulmonary disease taking BBs and those not taking BBs. Forty-nine studies were included, with a total sample size of 670 594. Among these, 12 studies were randomized controlled trials (RCTs; seven crossover and five parallel RCTs) and 37 studies were observational (including four post hoc analyses of data from RCTs). The hazard ratios (HRs) of chronic obstructive pulmonary disease exacerbation between patients with chronic obstructive pulmonary disease who were not treated with BBs and those who were treated with BBs, cardioselective BBs, and noncardioselective BBs were 0.77 [95% confidence interval (CI) 0.67, 0.89], 0.72 [95% CI 0.56, 0.94], and 0.98 [95% CI 0.71, 1.34, respectively] (HRs <1 indicate favouring BB therapy). The HRs of all-cause mortality between patients with chronic obstructive pulmonary disease who were not treated with BBs and those who were treated with BBs, cardioselective BBs, and noncardioselective BBs were 0.70 [95% CI 0.59, 0.83], 0.60 [95% CI 0.48, 0.76], and 0.74 [95% CI 0.60, 0.90], respectively (HRs <1 indicate favouring BB therapy). Patients with Chronic obstructive pulmonary disease treated with cardioselective BBs showed no difference in ventilation effect after the use of an agonist, in comparison with placebo. The difference in mean change in forced expiratory volume in 1 s was 0.06 [95% CI -0.02, 0.14]. CONCLUSION: The use of BBs in patients with chronic obstructive pulmonary disease is not only safe but also reduces their all-cause and in-hospital mortality. Cardioselective BBs may even reduce chronic obstructive pulmonary disease exacerbations. In addition, cardioselective BBs do not affect the action of bronchodilators. Importantly, BBs reduce the heart rate acceleration caused by bronchodilators. BBs should be prescribed freely when indicated in patients with chronic obstructive pulmonary disease and heart disease.

7.
Adv Physiol Educ ; 44(4): 726-733, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33155832

RESUMO

Current interdisciplinary medical training calls for reforms and innovations in the assessment of pathophysiology education. Formative assessment is used to monitor student learning to provide ongoing feedback that can improve both learning and teaching. Beginning in 2016, we implemented a formative assessment composed of case-based multiple-choice questions (MCQs) for all students in all majors. In 2017, case study questions began to be employed in the formative assessment, and student-set, case-based questions were further introduced. Aiming to gather the students' suggestions and feedback on the mixed-method assessment, we conducted a survey on aspects such as the effectiveness of the assessment, assessment content and completion, opinions on student-set questions, and the impact on pathophysiology learning for students from 2017 to 2019. In addition, we compared students' semesterly final scores with those of previous students and evaluated the relationship between formative and summative assessment scores. The results for 1,277 students clearly showed that the reformed formative assessment system was well received by the students. The students thought that the formative assessment not only allowed for the provision of real-time feedback on the effectiveness of teaching and learning but also nurtured self-motivation, the development of analytical and problem-solving skills, and collaborative efforts. Both the semesterly final scores and the proportions of students scoring in higher score ranges increased after the implementation of the formative assessment, and the summative assessment scores were positively related to the formative assessment scores. Consequently, the reformed formative assessment system significantly improved the quality of pathophysiology education.

8.
Arch Oral Biol ; 120: 104947, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33113460

RESUMO

OBJECTIVE: Hyposalivation is a common symptom of diabetes. Although microRNAs (miRNAs) play a role in the pathogenesis of diabetes, the specific effects of miRNAs on diabetic salivary glands are not clear. DESIGN: We used high-throughput technologies to screen differentially expressed (DE) miRNAs and mRNAs in submandibular gland (SMG) tissues from db/db mice and db/m mice. DE miRNAs and mRNAs were confirmed using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Twenty-eight DE miRNAs and 1146 DE mRNAs were identified between the SMG tissues of db/db mice and db/m mice. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated that the DE miRNAs were highly associated with terms related to diverse biological processes and signalling pathways. Of the related pathways, the tight junction pathway, autophagy pathway and transforming growth factor-ß (TGF-ß) signalling pathway were notable. AKT serine/threonine kinase 3 (AKT3) and phosphoinositide-3 kinase catalytic subunit delta (PIK3CD) may also play important roles in the development of diabetes-mediated hyposalivation. CONCLUSIONS: Our research described the miRNA-mRNA expression profiles and miRNA-mRNA network in the SMG tissues of db/db mice. These results provide possible molecular mechanisms of diabetes-induced hyposalivation and information for further studies.

9.
Oral Dis ; 2020 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-32892462

RESUMO

OBJECTIVE: In this study, we sought to determine the expression profiles of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) and construct functional networks to analyze their potential roles following botulinum toxin type A (BTXA)-mediated inhibition of salivary secretion. METHODS: The submandibular gland of rats in the BTXA and control groups was injected with BTXA and saline, respectively. Microarray analysis was used to identify the differentially expressed lncRNAs and mRNAs. Gene ontology and pathway analysis were performed to examine the biological functions. Functional networks, including lncRNA-mRNA co-expression and competing endogenous RNA (ceRNA) networks, were constructed to reveal the interaction between the coding and non-coding genes. RESULTS: Microarray analysis revealed that 254 lncRNAs and 631 mRNAs were differentially expressed between the BTXA and control groups. Bioinformatic analysis revealed that most of the mRNAs were closely related to transmembrane transporter activity. lncRNA-mRNA co-expression and ceRNA networks were constructed, and several critical mRNA-lncRNA axes and key microRNAs related to salivary secretion were identified. CONCLUSIONS: Our study identified differentially expressed lncRNAs and mRNAs through microarray analysis and explored the interactions between the coding and non-coding genes through bioinformatic analysis. These findings provide new insights into the mechanism of BTXA-mediated inhibition of salivary secretion.

10.
Ann Palliat Med ; 9(4): 1782-1796, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32527124

RESUMO

BACKGROUND: Lung cancer is the most common malignant tumor, and it remains the major cause of cancerrelated death worldwide. Anaplastic lymphoma kinase fusion gene-rearrangement (ALK-positive) nonsmall cell lung cancer (NSCLC) is a unique subgroup that accounts for 3-7% of NSCLC cases. Over the last few years, the introduction of several ALK inhibitors has completely altered the treatment of advanced ALK-positive NSCLC and significantly improved the prognosis for patients. Crizotinib was the first ALK inhibitor developed, and it has demonstrated systemic efficacy and strongly improved outcomes in NSCLC patients with ALK-positive when compared with chemotherapy. Alectinib was designed specifically to be a more potent and selective anti-ALK therapeutic agent that could bypass crizotinib resistance. This study aims to evaluate the different efficacies of alectinib and crizotinib on progression-free survival (PFS), central nervous system (CNS) progression and adverse events (AEs) in NSCLC patients with ALK-positive. METHODS: We searched for relevant literature in four electronic databases: PubMed, EMBASE, Cochrane Library, and Web of Science. The hazard ratio (HR) was calculated, and the effect of alectinib and crizotinib on PFS was evaluated. The quality of the studies was assessed using the Cochrane Risk of Bias tool. Publication bias was assessed using the Begg rank correlation test and the Egger weighted linear regression test. We performed the sensitivity analysis using the method of "removing one study". All analyses were performed in STATA. RESULTS: Ten studies were included, and the total sample size was 2,377. Alectinib showed significant PFS superiority over crizotinib. The pooled HR =0.41 (95% CI: 0.29-0.53) indicated that the alectinib therapy group did have significantly longer PFS than that of the crizotinib group. Based on 5 clinical trials, the cumulative incidence of CNS progression for patients treated with alectinib at 6 months (10%, 95% CI: 5-16%) and 12 months (16%, 95% CI: 9-24%) was calculated. Based on 7 clinical studies, the risk of AEs related to treatment with alectinib was determined: alectinib was associated with 28 cases of AE grade ≤2 and 9 cases of AE grade ≥3; among the top 4 incidences of AE grade ≥3, were blood creatine phosphokinase increased 5.6%, ALT increased 2.5%, AST increased 2.4% and Anemia 1.8%. CONCLUSIONS: Alectinib significantly prolongs PFS and it better controls CNS metastases than crizotinib and good toxicity characteristics in the first-line treatment of NSCLC patients with ALK-positive.

11.
J Clin Pharm Ther ; 45(6): 1363-1371, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32598559

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Bevacizumab (BVZ) is an angiogenesis inhibitor that often works well with chemotherapeutic drugs for the treatment of solid intracranial tumours in children. This meta-analysis discusses the efficacy and side effects of BVZ combined with irinotecan in the treatment of patients (younger than 21 years of age) with recurrent, progressive or refractory intracranial tumours. METHODS: We searched for articles published before 31 October 2018 in PubMed, EMBASE, Cochrane library and Web of Science. We selected relevant literature on the combination of BVZ and irinotecan in the treatment of children with intracranial tumours. Objective response was evaluated by combining partial response (PR), complete response (CR), stable disease (SD) and progressive disease (PD), and survival time was evaluated by combining overall survival (OS) and progression-free survival (PFS); common side effects were also analysed. All data included were obtained from single-arm data, with no control groups. RESULTS AND DISCUSSION: A total of 13 studies involving 272 patients were included. We found that out of 41% patients who showed an objective response following the BVZ therapy combined with irinotecan, 28% achieved a PR, 13% achieved a CR, 32% showed a SD, and 43% had a PD; PFS and OS were 6.47 and 11.9 months, respectively; gastrointestinal dysfunction, leukopenia and hypertension were the three most common adverse events, accounting for 36.7%, 33.6% and 22.1%, respectively, whereas musculoskeletal disorders had the lowest occurrence, accounting for 3.9%. WHAT IS NEW AND CONCLUSION: BVZ combined with irinotecan-based chemotherapy had a better response and prolonged survival in the treatment of paediatric intracranial tumours than radiation therapy or chemotherapy. Gastrointestinal dysfunction, leukopenia and hypertension were the toxic side effects with the highest incidence.

12.
Cardiovasc Drugs Ther ; 34(5): 591-604, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32424654

RESUMO

PURPOSE: Cardiac fibrosis is characterized by net accumulation of extracellular matrix (ECM) components in the  myocardium and facilitates the development of heart failure. C1q/tumor necrosis factor-related protein 15 (CTRP15) is a novel member of the CTRP family, and its gene expression is detected in adult mouse hearts. The present study was performed to determine the effect of CTRP15 on pressure overload-induced fibrotic remodeling. METHODS: Mice were subjected to transverse aortic constriction (TAC) surgery, and adeno-associated virus serotype 9 (AAV9)-carrying mouse CTRP15 gene was injected into mice to achieve CTRP15 overexpression in the myocardium. Adenovirus carrying the gene encoding CTRP15 or small interfering RNA (siRNA) of interest was infected into cultured neonatal mouse ventricular cardiomyocytes (NMVCs) or cardiac fibroblasts (CFs). Gene expression was measured by quantitative real-time PCR, and protein expression and distribution were determined by Western blotting, immunocytochemistry, and immunofluorescence staining. RESULTS: CTRP15 was predominantly produced by cardiac myocytes. CTRP15 expression in the left ventricles was downregulated in mice that underwent TAC. AAV9-mediated CTRP15 overexpression alleviated ventricular remodeling and dysfunction in the pressure-overloaded mice. Treatment of CFs with recombinant CTRP15 or the conditioned medium containing CTRP15 inhibited transforming growth factor (TGF)-ß1-induced Smad3 activation and myofibroblast differentiation. CTRP15 increased phosphorylation of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), and Akt. Blockade of IR/IRS-1/Akt pathway reversed the inhibitory effect of CTRP15 on TGF-ß1-induced Smad3 activation. CONCLUSION: CTRP15 exerts an anti-fibrotic effect on pressure overload-induced cardiac remodeling. The activation of IR/IRS-1/Akt pathway contributes to the anti-fibrotic effect of CTRP15 through targeting Smad3.


Assuntos
Cardiomiopatias/prevenção & controle , Citocinas/metabolismo , Fibroblastos/efeitos dos fármacos , Proteínas Musculares/metabolismo , Miócitos Cardíacos/metabolismo , Comunicação Parácrina , Fator de Crescimento Transformador beta1/farmacologia , Função Ventricular Esquerda , Remodelação Ventricular , Animais , Cardiomiopatias/genética , Cardiomiopatias/metabolismo , Cardiomiopatias/patologia , Células Cultivadas , Citocinas/genética , Modelos Animais de Doenças , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibrose , Masculino , Camundongos Endogâmicos C57BL , Proteínas Musculares/genética , Miócitos Cardíacos/patologia , Transdução de Sinais
13.
J Anat ; 237(3): 556-567, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32374057

RESUMO

Tight junction (TJ) plays an important role in regulating paracellular fluid transport in salivary glands; however, little is known about the involvement of TJs in diabetes salivary glands. This study aimed to investigate the alterations of TJs and their possible contribution in diabetes-induced hyposalivation. Here, we observed that the morphologies of submandibular glands (SMGs) were impaired, characterized by enlarged acini accumulation with giant secretory granules, which were significantly reduced in atrophic ducts in SMGs of db/db mice, a spontaneous model of type-2 diabetes. However, the secretory granules were increased and scattered in the acini of diabetes parotid glands (PGs). Other ultrastructural damages including swollen mitochondria, expansive endoplasmic reticulum, and autophagosomes were observed in the diabetes group. The levels of TJ proteins including claudin-1 (Cldn1) and claudin-3 (Cldn3) were increased, whereas those of claudin-4 (Cldn4), occludin (Ocln), and zonula occludens-1 (ZO-1) were decreased in SMGs of db/db mice. Higher Cldn1 and Cldn3 and lower claudin-10 (Cldn10) and Ocln levels were observed in PGs of diabetes mice. Taken together, the structures of SMGs and PGs were impaired in diabetes mice, and the disruption of TJ integrity in both SMGs and PGs may contribute to diabetes-induced hyposalivation.

14.
J Cell Physiol ; 235(1): 232-244, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31190343

RESUMO

Diabetes is often accompanied by dysfunction of salivary glands. However, the molecular mechanism remains unclear. The mechanisms that underlie diabetic hyposalivation were studied by db/db mice and SMG-C6 cells. We found morphological changes and decreased stimulated salivary flow rates of the submandibular gland (SMG) in diabetic mice. We observed structural changes and dysfunction of mitochondria. More mitophagosomes and higher expression of autophagy-related proteins were detected. Increased levels of proteins PINK1 and Parkin indicate that PINK1/Parkin-mediated mitophagy was activated in diabetic SMG. Consistently, high glucose (HG) induced mitochondrial dysfunction and PINK1/Parkin-mediated mitophagy in cultivated SMG-C6 cells. HG also increased reactive oxygen species (ROS) and lessened activation of antioxidants in SMG-C6 cells. In addition, HG lowered ERK1/2 phosphorylation and HG-induced mitophagy was decreased after ERK1/2 was activated by LM22B-10. Altogether, these data suggest that ROS played a crucial role in diabetes-induced mitochondrial dysfunction and PINK1/Parkin-mediated mitophagy and ERK1/2 was required in HG-induced mitophagy in SMG.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Mitofagia/efeitos dos fármacos , Proteínas Quinases/metabolismo , Glândulas Salivares/citologia , Ubiquitina-Proteína Ligases/metabolismo , Xerostomia/complicações , Animais , Linhagem Celular , Glucose/toxicidade , Camundongos , Camundongos Endogâmicos NOD , Mitocôndrias/metabolismo , Mitofagia/fisiologia , Proteínas Quinases/genética , Ratos , Glândulas Salivares/efeitos dos fármacos , Ubiquitina-Proteína Ligases/genética
15.
J Cancer ; 10(25): 6233-6243, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772656

RESUMO

Objectives: Intro-arterial chemotherapy combined with radiotherapy (IACRT) for the treatment of head and neck cancer (HNC) underwent a revival in recent years. Although many clinical trials have reported favorable outcomes, the effect of IACRT for HNC is still controversial. Therefore, this study was designed to evaluate the efficacy and safety of IACRT for HNC. Methods: The relevant articles published before August 2019 were searched from PubMed, Embase, Cochrane Library, Web of Science and PMC databases. Data were extracted and the combined complete response (CR), overall survival (OS) and toxicity incidence with 95% credible interval (CI) were examined from eligible studies. Results: Thirty-four studies comprising 1890 patients were included. IACRT achieved high CR (0.81, 95% CI: 0.76-0.86, P < 0.001), 3-year OS (0.75, 95% CI: 0.68-0.82, P < 0.001) and 5-year OS (0.68, 95% CI: 0.61-0.75, P < 0.001). The 3-year OS rate of stage III cancer (0.75, 95% CI: 0.53-0.97, P< 0.001) was higher than stage IV (0.52, 95% CI: 0.37-0.66, P = 0.025). Meanwhile, the 5-year OS of T3 cancer (0.87, 95% CI: 0.73-1.01, P = 0.028) was higher than T4 (0.53, 95% CI: 0.42-0.63, P = 0.286). Additionally, oral diseases, mucositis, leukopenia and dermatitis were the major toxicities of IACRT, which were all reversible. Conclusion: IACRT is an efficient and safe modality for HNC, which could achieve favorable cancer response and higher survival rate with acceptable toxicities, even for advanced HNC.

16.
J Neurol ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664548

RESUMO

BACKGROUND: Ischemic stroke (IS) is a common cause of death from vascular diseases. Studies have found that smoking increases the risk of ischemic stroke, but the association of smoking with the outcome of IS remains unclear. This meta-analysis aims to investigate the effect of smoking on the prognosis of IS. METHODS: We searched four electronic databases including PubMed, EMBASE, Cochrane library and Web of science for papers, published before January 2019. In this meta-analysis, Review Manager 5.3 software was used to calculate for the pooled estimate effect, as well as the inverse-variance method for pooled mean difference (MD) and odds ratio (OR) of incidence in two groups of population. RESULTS: A total of 14,789 citations were identified during the literature search, 21 studies were included in the meta-analyses after screening. The full-adjusted OR of poor prognostic outcome in smoking and nonsmoking patients with stroke was pooled as 0.96 (95% CI 0.77-1.21), suggested that smoking or not has no impact on prognosis of IS. The pooled MD of onset age between smoking and nonsmoking IS patients was - 10.05 (- 12.91, - 7.19), indicated that smoking causes first onset of IS to occur 10 years earlier. CONCLUSIONS: This meta-analysis showed that smoking was not a protective factor for poor prognosis of IS. Smoking patients with IS are 10 years younger than nonsmoking patients at time of the first onset of stroke.

17.
Ther Adv Med Oncol ; 11: 1758835919855235, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31217825

RESUMO

Background: Adjuvant bisphosphonates reduce the rate of breast cancer recurrence in the bone and improve breast cancer survival. However, the risk of adverse events associated with bisphosphonate therapy for breast cancer remains poorly defined. Methods: A literature search was conducted using the PubMed, EMBASE, Cochrane and Web of Science libraries. Risk ratio (RR) was calculated to evaluate the adverse events of the meta-analytic results. Osteonecrosis of the jaw (ONJ) incidence was calculated using the random effect model (D+L pooled) for meta-analysis. Results: A total of 47 studies comprising 20,607 patients were included; 23 randomized controlled studies (RCTs) provided data of adverse events for bisphosphonate therapy versus without bisphosphonates. Bisphosphonates were significantly associated with influenza-like illness (RR = 4.52), fatigue (RR = 1.08), fever (RR = 1.82), dyspepsia (RR = 1.25), anorexia (RR = 1.29), and urinary tract infection (RR = 1.32). No differences were observed in other adverse events. We combined the incidence of ONJ in 24 retrospective studies to analyze the incidence of ONJ using bisphosphonates. The pooled probability of ONJ toxicity in the bisphosphonates group was 2%. Conclusions: Bisphosphonates were significantly associated with influenza-like illness, fatigue, fever, dyspepsia, anorexia, and urinary tract infection. Furthermore, bisphosphonates increase the risk of ONJ toxicity.

18.
Sci Rep ; 7(1): 14524, 2017 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-29109472

RESUMO

Hypertension is a systemic disorder that affects numerous physiological processes throughout the body. Improper sodium transport is a common comorbidity of hypertension, and sodium transport is also critical for maintaining the secretion of submandibular glands, whether the function of submandibular glands is affected by hypertension remains unclear. To determine whether hypertension induces changes in the protein expression of submandibular glands, we compared the proteome of submandibular glands from 14-week-old spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats using LC-MS/MS. The results revealed that 95 proteins displayed different levels of expression between the submandibular glands from the SHRs and WKYs. Among these, 35 proteins were more abundant, and 60 proteins were less abundant in the SHR compared with the WKY rats. Specifically, aquaporin 5 and parvalbumin, which are correlated with water transport and intracellular Ca2+ signal transduction, were verified to exhibit differences in protein abundance. Impaired Ca2+ response to carbachol was confirmed in the acinar cells from SHRs, and hyposecretion by the submandibular glands was further confirmed by in vivo saliva collection. In conclusion, the proteomic analysis of the submandibular glands of SHRs revealed novel changes in protein abundance that provides possible mechanisms connecting hypertension and hyposecretion in submandibular glands.


Assuntos
Aquaporina 5/metabolismo , Cálcio/metabolismo , Hipertensão/metabolismo , Glândula Submandibular/metabolismo , Animais , Sinalização do Cálcio/fisiologia , Cátions Bivalentes/metabolismo , Membrana Celular/metabolismo , Membrana Celular/patologia , Citosol/metabolismo , Expressão Gênica , Hipertensão/patologia , Masculino , Parvalbuminas/metabolismo , Proteoma , Proteômica , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Saliva/metabolismo , Glândula Submandibular/patologia
19.
J Mol Histol ; 48(2): 99-111, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28078480

RESUMO

Submandibular gland (SMG) autotransplantation is an effective therapy for treating severe dry eye syndrome. However, epiphora occurs in more than 40% of patients 6 months after operation. We previously found that muscarinic acetylcholine receptor (mAChR) plays a crucial role in regulating SMG secretion partially through the modulation on tight junction (TJ)-based paracellular pathway. Therefore, the present study aimed to investigate the possible involvement of mAChR and TJ in a rabbit long-term model of SMG transplantation. We found that SMG secretion was significantly increased on postoperative days 90 and 180, which imitated epiphora observed in the patients with SMG transplantation. Although the mRNA expression and fluorescence intensity of M1 and M3 mAChR subtypes were reversed to control levels on postoperative days 30, 90, and 180, the content of ß-arrestin2, but not ß-arrestin1, was gradually decreased after transplantation, which suggests that mAChR may be hypersensitive in late phase of SMG transplantation. The width of acinar TJs was enlarged and fluorescence intensity of F-actin in peri-apicolateral membranes were remarkably increased on postoperative days 90 and 180. Topical treatment with atropine gel significantly reduced SMG secretion, TJ width, as well as F-actin intensity in peri-apicolateral membranes on postoperative days 180. Moreover, in a perfused rabbit SMG, carbachol increased salivary secretion, enlarged TJ width, and induced F-actin rearrangement, whereas these responses were inhibited by atropine pretreatment. Taken together, our findings suggest that the hypersensitive mAChR may contribute to epiphora in late phase of SMG transplantation through modulating TJ-based paracellular permeability.


Assuntos
Doenças do Aparelho Lacrimal/etiologia , Receptores Muscarínicos/fisiologia , Glândula Submandibular/transplante , Junções Íntimas/patologia , Actinas , Animais , Atropina/farmacologia , Autoenxertos , Carbacol/farmacologia , Permeabilidade da Membrana Celular , Modelos Animais , Coelhos , Glândulas Salivares/metabolismo , Glândula Submandibular/metabolismo
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