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1.
Am J Hypertens ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32030405

RESUMO

BACKGROUND: The study was performed to investigate the impact of prehypertension defined by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) on the risk of major adverse cardiovascular events (MACE) in a Chinese rural cohort. METHODS: The epidemiological prospective cohort study included 38,765 participants aged≥35 years followed for a median of 12.5 years- divided into normal BP (n = 7,366), prehypertension (n = 18,095) and hypertension groups (n = 13,304) - were enrolled for the final analysis. Follow up for MACE including cardiovascular disease (CVD) death, stroke and myocardial infarction (MI). Adjusted Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: The age and sex-adjusted incidence of MACE and its subtypes rose progressively with elevation of BP levels (P < 0.001). After adjusting multivariable Cox proportional hazards, significant increases were observed from the prehypertensive group for incident MACE (HR = 1.337, 95% CI: 1.186-1.508, P < 0.001), CVD mortality (HR = 1.331, 95% CI: 1.109-1.597, P = 0.002) and stroke (HR = 1.424, 95% CI:1.237-1.639, P < 0.001) but not MI (P > 0.05) compared to normal BP. CONCLUSION: Prehypertensive individuals had a greater risk of incident MACE, CVD mortality and stroke, implying that improvements in BP monitoring and early intervention in individuals with prehypertension in rural China are urgently needed.

2.
Diagn Interv Imaging ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32063483

RESUMO

PURPOSE: To compare the performance of biparametric magnetic resonance imaging (bpMRI) to that of multiparametric MRI (mpMRI) in combination with prostate-specific antigen density (PSAD) in detecting clinically significant prostate cancer (csPCa) in patients with PSA serum levels of 4∼10ng/mL. MATERIALS AND METHODS: A total of 123 men (mean age, 66.3±8.9 [SD]; range: 42-83 years) with PSA serum levels of 4∼10ng/mL with suspected csPCa were included. All patients underwent mpMRI at 3 Tesla and transrectal ultrasound-guided prostate biopsy in their clinical workup and were followed-up for >1 year when no csPCa was found at initial biopsy. The mpMRI images were reinterpreted according to the Prostate Imaging Reporting and Data System (PI-RADS, v2.1) twice in two different sessions using either mpMRI sequences or bpMRI sequences. The patients were divided into 2 groups according to whether csPCa was detected. The PI-RADS (mpMRI or bpMRI) categories and PSAD were used in combination to detect csPCa. Receiver operating characteristic (ROC) curve and decision curve analyses were performed to compare the efficacy of the different models (mpMRI, bpMRI, PSAD, mpMRI+PSAD and bpMRI+PSAD). RESULTS: Thirty-seven patients (30.1%, 37/123) had csPCa. ROC analysis showed that bpMRI (AUC=0.884 [95% confidence interval (CI): 0.814-0.935]) outperformed mpMRI (AUC=0.867 [95% CI: 0.794-0.921]) (P=0.035) and that bpMRI and mpMRI performed better than PSAD (0.682 [95% CI: 0.592-0.763]) in detecting csPCa; bpMRI+PSAD (AUC=0.907 [95% CI: 0.841-0.952]) performed similarly to mpMRI+PSAD (AUC=0.896 [95% CI: 0.828-0.944]) (P=0.151) and bpMRI (P=0.224). The sensitivity and specificity were 81.1% (95% CI: 64.8-92.0%) and 88.4% (95% CI: 79.7-94.3%), respectively for bpMRI, and 83.8% (95% CI: 68.0-93.8%) and 80.2% (95% CI: 70.2-88.0%), respectively for mpMRI (P>0.999 for sensitivity and P=0.016 for specificity). Among the 5 decision models, the decision curve analysis showed that all models (except for PSAD) achieved a high net benefit. CONCLUSION: In patients with PSA serum levels of 4∼10ng/mL, bpMRI and bpMRI combined with PSAD achieve better performance than mpMRI in detecting csPCa; bpMRI has a higher specificity than mpMRI, which could decrease unnecessary biopsy, and may serve as a potential alternative to mpMRI to optimize clinical workup.

3.
Zhonghua Yi Xue Za Zhi ; 100(3): 182-186, 2020 Jan 21.
Artigo em Chinês | MEDLINE | ID: mdl-32008283

RESUMO

Objective: To analyze morphological changes in central sulcus of the cerebral cortex in children with complete growth hormone deficiency (CGHD). Methods: Patients attending the Shandong Provincial Hospital who were diagnosed with CGHD or idiopathic short stature were recruited from January 2015 to January 2019. Thirty children with CGHD (18 males and 12 females, 5 to 14 years old) and 30 children with idiopathic short stature (22 males and 8 females, 5 to 14 years old) were included. Measurements of the central sulcus, including the average width, maximum depth, average depth, top length, bottom length and depth position-based profiles (DPP), were obtained using Brain VISA software. The significant differences between groups were statistically analyzed. Results: The average width of bilateral central sulci in children with CGHD (left: (2.26±0.41) mm; right: (2.19±0.34) mm) were significantly higher than those in children with idiopathic short stature (left: (2.10±0.27) mm; right: (2.02±0.18) mm) (P<0.05) ; The maximum depth of the left central sulcus ((19.67±1.29) mm) and the average depth of the right central sulcus ((14.18±1.41) mm) were significantly lower than those in children with idiopathic short stature (left maximum depth: (20.69±1.43) mm; right average depth: (14.92±1.21) mm) (P<0.05) . Children with CGHD had significantly lower DPP at the middle part of the left central sulcus (sites: 46-54) and the inferior part of the right central sulcus(sites: 91-98). Conclusion: There are significant morphological changes of the central sulcus in children with CGHD, which may represent the structural basis of their relatively slower development in motor, cognitive and linguistic functional performance.


Assuntos
Encéfalo/patologia , Córtex Cerebral/anatomia & histologia , Hormônio do Crescimento/deficiência , Imagem por Ressonância Magnética/métodos , Adolescente , Encéfalo/fisiopatologia , Mapeamento Encefálico , Criança , Pré-Escolar , Feminino , Humanos , Masculino
4.
Cell Rep ; 30(5): 1300-1309.e5, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32023450

RESUMO

Ependymomas exist within distinct genetic subgroups, but the molecular diversity within individual ependymomas is unknown. We perform multiplatform molecular profiling of 6 spatially distinct samples from an ependymoma with C11orf95-RELA fusion. DNA methylation and RNA sequencing distinguish clusters of samples according to neuronal development gene expression programs that could also be delineated by differences in magnetic resonance blood perfusion. Exome sequencing and phylogenetic analysis reveal epigenomic intratumor heterogeneity and suggest that chromosomal structural alterations may precede accumulation of single-nucleotide variants during ependymoma tumorigenesis. In sum, these findings shed light on the oncogenesis and intratumor heterogeneity of ependymoma.

5.
Epidemiol Infect ; 148: e26, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32046804

RESUMO

Studies in countries with high immunisation coverage suggest that the re-emergence of pertussis may be caused by a decreased duration of protection resulting from the replacement of whole-cell pertussis vaccine (WPV) with the acellular pertussis vaccine (APV). In China, WPV was introduced in 1978. The pertussis vaccination schedule advanced from an all-WPV schedule (1978-2007), to a mixed WPV/APV schedule (2008-2009), then to an all-APV schedule (2010-2016). Increases in the incidence of pertussis have been reported in recent years in Jinan and other cities in China. However, there have been few Chinese-population-based studies focused on the impact of schedule changes. We obtained annual pertussis incidences from 1956 to 2016 from the Jinan Notifiable Conditions Database. We used interrupted time series and segmented regression analyses to assess changes in pertussis incidence at the beginning of each year, and average annual changes during the intervention. Pertussis incidence decreased by 1.11 cases per 100 000 population (P = 0.743) immediately following WPV introduction in 1978 and declined significantly by 1.21 cases per 100 000 population per year (P < 0.0001) between 1978 and 2001. Immediately after APV replaced the fourth dose of WPV in 2008, the second and third doses in 2009, then replaced all four doses in 2010, pertussis incidence declined by 1.98, 1.98 and 1.08 cases per 100 000 population, respectively. However, the results were not statistically significant. There were significant increasing trends in pertussis incidence after APV replacements: 1.63, 1.77 and 1.78 cases/year in 2008-2016, 2009-2016 and 2010-2016, respectively. Our study shows that the impact of an all-WPV schedule may be less than the impacts of the sequential WPV/APV schedules. The short-term impact of APV was better than that of WPV; however, the duration of APV-induced protection was not ideal. The impact and duration of protective immunity resulting from APVs produced in China need further evaluation. Further research on the effectiveness of pertussis vaccination programme in Jinan, China is also necessary.

6.
Zhonghua Gan Zang Bing Za Zhi ; 28(1): 47-52, 2020 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-32023699

RESUMO

Objective: To establish and evaluate diagnostic efficacy and applicability of serum Golgi protein (GP) 73 based non-invasive diagnostic model with other conventional serological indicators for compensated stage hepatitis B cirrhosis. Methods: 666 cases with chronic hepatitis B (CHB) who had visited to the Fifth Medical Center of People's Liberation Army General Hospital from January 2010 to December 2017 were selected as the study subjects, and were classified according to compensated stage cirrhosis into clinical and pathological diagnosis group based on whether or not the liver histological examination was performed. A diagnostic model of compensated stage hepatitis B cirrhosis in the clinical diagnosis group was established. The current clinically used diagnostic model of liver cirrhosis, aspartate aminotransferase/platelet ratio index (APRI), fibrosis index (FIB)-4 and liver stiffness measurement (LSM) were compared. Eventually, the diagnostic model was verified step by step by pathological diagnosis group. Results: The area under the receiver operating characteristic curve (AUC) of GP73 and APRI, FIB-4, and LSM for cirrhosis patients in the clinical diagnosis group were 0.842, 0.857, 0.864, and 0.832, respectively. The diagnostic efficiency of the four indicators were of similar (P value > 0.05). A diagnostic model of compensated stage hepatitis B cirrhosis (GAPA) using logistic regression analysis was established: LogitP = 1/ [1 + exp (1.614-0.054 × GP73-0.045 × Age + 0.030 × PLT-0.015 × ALP)]. The AUC of the model was as high as 0.940 and the optimal cut-off value were 0.41. The corresponding diagnostic sensitivity and specificity were 0.92 and 0.82, respectively. The diagnostic efficiency was better than that of APRI, FIB-4, LSM and GP73 alone (P < 0.05). The AUC of GAPA was 0.877 in the pathological diagnosis group, which was similar to the diagnostic efficacy of LSM (0.891) and FIB-4 (0.847) (P > 0.1), but still superior to that of APRI (0.811) and GP73 alone (0.780) (P < 0.001). Conclusion: GAPA, a diagnostic model for compensated stage hepatitis B cirrhosis established in this study, has a good diagnostic efficacy in both the clinical and pathological diagnosis group, and has certain auxiliary diagnostic value in the areas where resources are relatively scarce or where LSM has not been developed.


Assuntos
Biomarcadores/metabolismo , Cirrose Hepática/diagnóstico , Fígado/metabolismo , Proteínas de Membrana/metabolismo , Aspartato Aminotransferases/metabolismo , Biópsia , Fibrose , Hepatite B , Humanos , Fígado/patologia , Proteínas de Membrana/sangue , Curva ROC , Índice de Gravidade de Doença
7.
Eur Rev Med Pharmacol Sci ; 24(1): 1-10, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31957812

RESUMO

OBJECTIVE: The aim of this study was to investigate whether microRNA-1286 could inhibit the osteogenic differentiation of human marrow mesenchymal stem cells (hMSCs) by regulating FZD4 expression and promoting the progression of osteoporosis. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression of microRNA-1286 in the serum of patients with osteoporosis. Meanwhile, microRNA-1286 expression in different stages of osteogenic differentiation of hMSCs was measured by qRT-PCR as well. After overexpression of microRNA-1286 and FZD4 in hMSCs, the mRNA expression levels of microRNA-1286, alkaline phosphatase (ALP), RUNX2 and osteocalcin (OCN) were detected by qRT-PCR. The protein expression levels of RUNX2 and OCN were detected by Western blot. Meanwhile, alkaline phosphatase (ALP) activity and expression in cells were examined using ALP assay kit and ALP staining method, respectively. Cell mineralized nodules were detected through the alizarin red staining test. Bioinformatics method was used to predict the binding site of microRNA-1286 to FZD4. Subsequent luciferase reporter gene assay was performed to verify whether microRNA-1286 could combine with FZD4. After overexpression or knockdown of microRNA-1286, the mRNA and protein expressions of FZD4 were analyzed using qRT-PCR and Western blot assay, respectively. After the simultaneous overexpression of microRNA-1286 and FZD4 in hMSCs, the mRNA expression levels of ALP, RUNX2 and OCN, ALP activity and content, and cell mineralization ability were successively examined. RESULTS: The expression of microRNA-1286 in the serum of patients with osteoporosis was significantly higher than that of the normal population. Meanwhile, microRNA-1286 expression decreased with the increase of osteogenic differentiation days of hAMSCs. After the overexpression of microRNA-1286, ALP, RUNX2, and OCN levels, ALP activity, RUNX2, and OCN protein levels, as well as mineralized nodule formation were significantly reduced. However, results were reversed when FZD4 was simultaneously up-regulated. Luciferase reporter gene assay results verified that microRNA-1286 could bind to FZD4. After the overexpression of microRNA-1286, the mRNA and protein expressions of FZD4 were found significantly down-regulated. However, results were reversed after knocking down microRNA-1286. Furthermore, the simultaneous overexpression of microRNA-1286 and FZD4 could counteract the inhibitory effect of over-expression of microRNA-1286 on osteogenic differentiation of hMSCs. CONCLUSIONS: MicroRNA-1286 can regulate FZD4 expression and inhibit osteogenic differentiation of hMSCs, thereby promoting the development of osteoporosis.

8.
Ann Oncol ; 31(2): 310-317, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31959349

RESUMO

BACKGROUND: The addition of atezolizumab to carboplatin and etoposide (CP/ET) significantly improved progression-free and overall survival for patients with extensive-stage small-cell lung cancer (ES-SCLC) in the IMpower133 study (NCT02763579). We have evaluated adverse events (AEs) and patient-reported outcomes in IMpower133 to assess the benefit-risk profile of this regimen. PATIENTS AND METHODS: Patients received four 21-day cycles of CP/ET plus intravenous atezolizumab 1200 mg or placebo (induction phase), followed by atezolizumab or placebo (maintenance phase) until progression or loss of benefit. AEs were assessed and patient-reported outcomes were evaluated every 3 weeks during treatment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (QLQ-C30) and QLQ-LC13. RESULTS: Overall, 394 patients were assessable for safety in the induction phase and 318 in the maintenance phase. The frequency of AEs, grade 3-4 AEs, and serious AEs was similar between arms in both phases. Immune-related AEs were more frequent in the atezolizumab arm during both induction (28% versus 17%; leading to atezolizumab/placebo interruption 9% versus 5%, leading to withdrawal 4% versus 0%) and maintenance (26% versus 15%; leading to atezolizumab/placebo interruption, 3% versus 2%, leading to withdrawal 1% versus 1%), most commonly rash (induction 11% versus 9%, maintenance 14% versus 4%), and hypothyroidism (induction 4.0% versus 0%, maintenance 10% versus 1%). Changes in patient-reported treatment-related symptoms commonly associated with quality of life impairment were generally similar during induction and most of the maintenance phase. Patient-reported function and health-related quality of life (HRQoL) improved in both arms after initiating treatment, with more pronounced and persistent HRQoL improvements in the atezolizumab arm. CONCLUSIONS: In patients with ES-SCLC, atezolizumab plus CP/ET has a comparable safety profile to placebo plus CP/ET, and the addition of atezolizumab did not adversely impact patient-reported HRQoL. These data demonstrate the positive benefit-risk profile of first-line atezolizumab plus CP/ET in ES-SCLC and further support this regimen as a new standard of care in this setting. CLINICAL TRIALS NUMBER: NCT02763579.

9.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(1): 69-75, 2020 Jan 06.
Artigo em Chinês | MEDLINE | ID: mdl-31914572

RESUMO

Objective: To understand the consciousness of the cancer early treatment and its demographic and socioeconomic factors. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China (CanSPUC) from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. The questionnaire collected personal information, the consciousness of the cancer early treatment and relevant factors. The Chi square test was used to compare the difference between the consciousness of the cancer early treatment and relevant factors among the four groups. The logistic regression model was used to analyze the influencing factors related to the consciousness of the cancer early treatment. Results: With the assumption of being diagnosed as precancer or cancer, 89.97% of community residents, 91.84% of cancer risk assessment/screening population, 93.00% of cancer patients and 91.52% of occupational population would accept active treatments (P<0.001). If the immediate family members were diagnosed as precancer or cancer, people who would encourage their family members to receive early treatment in the four groups accounted for 91.96%, 91.94%, 92.44% and 91.55%, respectively (P<0.001). The company employees, annual household income with 40 000 yuan and more and other three groups had a relatively better consciousness of the cancer early treatment (P<0.05). Male, widowed, unemployed and from the central and western regions had a relatively worse consciousness of the cancer early treatment (P<0.05). Conclusion: Residents in urban China participants had a good consciousness of the cancer early treatment. The marital status, occupation, annual household income and residential regions were major factors related to the consciousness of the cancer early treatment.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Neoplasias/terapia , Tempo para o Tratamento/estatística & dados numéricos , População Urbana , Adolescente , Adulto , China , Estudos Transversais , Feminino , Humanos , Masculino , Fatores Socioeconômicos , População Urbana/estatística & dados numéricos
10.
Philos Trans R Soc Lond B Biol Sci ; 375(1794): 20190128, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-31983334

RESUMO

Integrated high-resolution maps of carbon stocks and biodiversity that identify areas of potential co-benefits for climate change mitigation and biodiversity conservation can help facilitate the implementation of global climate and biodiversity commitments at local levels. However, the multi-dimensional nature of biodiversity presents a major challenge for understanding, mapping and communicating where and how biodiversity benefits coincide with climate benefits. A new integrated approach to biodiversity is therefore needed. Here, we (a) present a new high-resolution map of global above- and below-ground carbon stored in biomass and soil, (b) quantify biodiversity values using two complementary indices (BIp and BIr) representing proactive and reactive approaches to conservation, and (c) examine patterns of carbon-biodiversity overlap by identifying 'hotspots' (20% highest values for both aspects). Our indices integrate local diversity and ecosystem intactness, as well as regional ecosystem intactness across the broader area supporting a similar natural assemblage of species to the location of interest. The western Amazon Basin, Central Africa and Southeast Asia capture the last strongholds of highest local biodiversity and ecosystem intactness worldwide, while the last refuges for unique biological communities whose habitats have been greatly reduced are mostly found in the tropical Andes and central Sundaland. There is 38 and 5% overlap in carbon and biodiversity hotspots, for proactive and reactive conservation, respectively. Alarmingly, only around 12 and 21% of these proactive and reactive hotspot areas, respectively, are formally protected. This highlights that a coupled approach is urgently needed to help achieve both climate and biodiversity global targets. This would involve (1) restoring and conserving unprotected, degraded ecosystems, particularly in the Neotropics and Indomalaya, and (2) retaining the remaining strongholds of intactness. This article is part of the theme issue 'Climate change and ecosystems: threats, opportunities and solutions'.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31987962

RESUMO

PURPOSE: Dose-escalated XXXX to the whole prostate may be associated with better outcomes, but at a risk of increased toxicity. An alternative approach is to focally boost the dominant intraprostatic lesion (DIL) seen on MRI. We report the toxicity and quality of life (QOL) outcomes of two phase II trials of prostate and pelvic XXXX, with or without a simultaneous DIL boost. METHODS: The first trial treated patients with high-risk prostate cancer (PCa) to a dose of 40 Gy to the prostate and 25 Gy to the pelvis in 5 fractions. The second trial treated patients with intermediate-risk and high-risk PCa to a dose of 35 Gy to the prostate, 25 Gy to the pelvis, and a DIL boost up to 50 Gy in 5 fractions. Acute toxicities, late toxicities and QOL were assessed. RESULTS: 30 patients were enrolled in each trial. In the focal boost cohort, the median DIL D90% was 48.3 Gy. There was no significant difference in acute grade ≥2 GI or GU toxicity between the two trials, or cumulative worst late GI or GU toxicity up to 24 months. There was no significant difference in QOL domain scores or minimally clinical important change between the two trials. CONCLUSIONS: Prostate and pelvic XXXX with a simultaneous DIL boost was feasible. Acute grade ≥2 toxicity, late toxicity, and QOL seems to be comparable to a cohort that did not receive a focal boost. Further follow-up will be required to assess long-term outcomes, and randomized data is required to confirm these findings.

12.
Artigo em Chinês | MEDLINE | ID: mdl-31954386

RESUMO

Objective: The consistency of 24-hour oropharyngeal Dx-pH monitoring and proton pump inhibitor(PPI) test in the diagnosis of laryngopharyngeal reflux disease (LPRD) was investigated. Methods: Sixty patients with laryngopharyngeal reflux (LPR) related symptoms who had never received PPI treatment were assessed by reflux symptom index (RSI) and reflux finding score (RFS) between October 2017 and October 2018, including 28 males and 38 females, aged from 16 to 72 years, with a medium age of 38 years. Prior to treatment, all patients were evaluated with 24 hours oropharyngeal Dx-pH monitoring(Restech). After empiric therapy with PPI twice-daily for 8 weeks, the efficacy was evaluated according to posttreatment RSI score.The data was analysed with Kruskal-Wallis test, Student Newman Keuls test and consistency check. Results: (1)Among all 60 patients,13 patients (21.7%) had pathologic Ryan score and all resulted responsive to PPI;27 patients (45.0%) with a negative Ryan score were unresponsive to PPI; 20 patients (33.3%) despite a negative Ryan score resulted responsive to PPI therapy. Considering responsiveness to PPI therapy as the gold standard for the diagnosis of LPRD, the sensitivity, specificity, positive predictive value and negative predictive value of Ryan score were 39.4%, 100%, 100% and 57.4% respectively. The Kappa value was 0.369 (P<0.01). (2)Among 34 patients (56.7%) with positive Dx-pH results (24-hour oropharyngeal acid reflux events≥ 3 times), 29 patients were positive and 5 patients were negative in PPI test. Among 26 patients with negative Dx-pH results (24-hour oropharyngeal acid reflux events<3 times), 4 patients were positive and 22 patients were negative in PPI test. Considering responsiveness to PPI therapy as the gold standard for the diagnosis of LPRD, the sensitivity, specificity, positive predictive value and negative predictive value of 24-hour oropharyngeal acid reflux events were 87.9%, 81.5%, 85.3% and 84.6% respectively. The Kappa value was 0.696(P<0.01). Conclusions: There is a positive correlation between 24-hour oropharyngeal Dx-pH monitoring positive results (24-hour oropharyngeal acid reflux events≥3 times) and PPI test in the diagnosis of LPRD. The 24-hour oropharyngeal Dx-pH monitoring can be a promising tool for the diagnosis of suspected LPRD patients, and more sensitive and accurate Dx-pH diagnostic index will be required in the clinic.


Assuntos
Monitoramento do pH Esofágico/métodos , Refluxo Laringofaríngeo/diagnóstico , Inibidores da Bomba de Prótons/uso terapêutico , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Adulto Jovem
14.
Clin Exp Immunol ; 199(2): 172-181, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31652350

RESUMO

Tertiary lymphoid structure (TLS) provides a local and critical microenvironment for both cellular and humoral immunity and supports effective antigen presentation and lymphocyte activation. However, the gene expression profile and prognostic significance of TLS in oral cancer remain largely unrevealed. In this study, we found the presence of both intratumoral and peritumoral TLSs in a series of 65 patients with oral cancer treated by surgical resection, with positive detection rates of 33.8 and 75.4%, respectively. The presence of intratumoral TLSs, but not peritumoral TLSs, was significantly associated with decreased P53 and Ki67 scores (P = 0·027 and 0·047, respectively). The survival analyses revealed that oral cancer patients with higher grades of TLSs was associated with improved disease-free survival (DFS) and overall survival (OS) (P = 0·037 and 0·031, respectively). Gene expression profiling analysis of the cytokines and chemokines responsible for lymph-node neogenesis identified a three-up-regulated-gene set, i.e. IL7, LTB and CXCL13, which was shown to be correlated with human oral cancer-associated TLSs. This study provides a framework for better understanding of oral cancer-associated TLSs and for delineating future innovative prognostic biomarkers and immune therapeutic strategies for oral cancer.

15.
Plant Cell Rep ; 39(1): 19-33, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31485784

RESUMO

KEY MESSAGE: WSL8 encoding a deoxyribonucleoside kinase (dNK) that catalyzes the first step in the salvage pathway of nucleotide synthesis plays an important role in early chloroplast development in rice. The chloroplast is an organelle that converts light energy into chemical energy; therefore, the normal differentiation and development of chloroplast are pivotal for plant survival. Deoxyribonucleoside kinases (dNKs) play an important role in the salvage pathway of nucleotides. However, the relationship between dNKs and chloroplast development remains elusive. Here, we identified a white stripe leaf 8 (wsl8) mutant that exhibited a white stripe leaf phenotype at seedling stage (before the four-leaf stage). The mutant showed a significantly lower chlorophyll content and defective chloroplast morphology, whereas higher reactive oxygen species than the wild type. As the leaf developed, the chlorotic mutant plants gradually turned green, accompanied by the restoration in chlorophyll accumulation and chloroplast ultrastructure. Map-based cloning revealed that WSL8 encodes a dNK on chromosome 5. Compared with the wild type, a C-to-G single base substitution occurred in the wsl8 mutant, which caused a missense mutation (Leu 349 Val) and significantly reduced dNK enzyme activity. A subcellular localization experiment showed the WSL8 protein was targeted in the chloroplast and its transcripts were expressed in various tissues, with more abundance in young leaves and nodes. Ribosome and RNA-sequencing analysis indicated that some components and genes related to ribosome biosynthesis were down-regulated in the mutant. An exogenous feeding experiment suggested that the WSL8 performed the enzymic activity of thymidine kinase, especially functioning in the salvage synthesis of thymidine monophosphate. Our results highlight that the salvage pathway mediated by the dNK is essential for early chloroplast development in rice.

16.
Plant Biol (Stuttg) ; 22 Suppl 1: 143-152, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30597713

RESUMO

Plastid casein kinase 2 (CK2), which is a major Ser/Thr-specific enzyme in higher organisms, plays an essential role in plant development and diverse abiotic stresses. CKB1 is a regulatory subunit beta of CK2. To expand our understand of functions of the CKB1 gene in Arabidopsis thaliana, protein changes among wild-type (WT) and CKB1 gain- and loss-of-function mutants were compared. Proteins extracted from the CKB1 knockout mutant and overexpressing mutant were compared with Col-0 plants using 2D-PAGE. Proteins regulated by CKB1 were identified with matrix-assisted laser desorption ionisation time-of-flight/time-of-flight mass spectrometry (MALDI-TOF/TOF), and its transcript was verified by qRT-PCR. Bioinformatics analysis, including gene ontology and protein-protein interaction analysis, were employed. The results of mass spectra and bioinformatics analysis suggest that CKB1 may have functions in regulation of the ribosomal protein L10 (RPL10) family and is involved in ultraviolet-B (UV-B) response. Furthermore, qRT-PCR verification showed CKB1 expression was up-regulated by UV-B stress. The expression levels of five genes in the RPL10 family were reduced in the ckb1 T-DNA insertion mutants, whereas they increased in the CKB1 overexpressing mutants under both normal conditions and UV-B treatment. In conclusion, CKB1 has important functions in UV-B radiation stress. Our study implies that CKB1 positively regulates UV-B radiation stress signalling, possibly through modulating expression of the RPL10 family.

17.
Neoplasma ; 67(1): 129-136, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31847523

RESUMO

The insulin growth factor 2 receptor (IGF2R) belongs to insulin growth factor (IGF) pathway and has been proposed as the tumor suppressor in many cancers. However, its role in bladder cancer is unknown. In the current study, we reported that IGF2R expression was decreased in bladder cancer tissues (p<0.05). Immunohistochemistry (IHC) and Cox regression analysis showed that low IGF2R expression was significantly associated with more advanced histological grade; high clinical stage; lymph node metastasis and poorer overall survival for patients with bladder cancer. Moreover, silencing IGF2R promoted cell proliferation of bladder cancer cells in vitro and in vivo (p<0.05). Furthermore, knockdown IGF2R resulted in higher phosphorylation level of AKT. The findings of this study indicated that IGF2R played a tumor suppressor role in bladder cancer. Downregulation IGF2R may promote tumor growth by activating AKT signaling pathway. IGF2R could be considered as a promising candidate for novel biomarker and therapeutic target for human bladder cancer.

19.
J Endocrinol Invest ; 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31820401

RESUMO

BACKGROUND: Previously published data on the association between the XRCC1 Arg194Trp polymorphism and thyroid cancer (TC) remain controversial. METHODS: To clarify the association between the XRCC1 Arg194Trp polymorphism and susceptibility to TC, a meta-analysis of case-control studies was conducted. We systematically searched PubMed and CNKI to identify relevant studies. Pooled odds ratios (ORs) of various genetic models were estimated using fixed and random effects models. Heterogeneity was detected by Q-statistic, and the Egger's test was used to evaluate the publication bias. RESULTS: A total of seven eligible studies for the XRCC1 Arg194Trp polymorphism (1500 patients and 2358 controls) were included in this meta-analysis. The results of our study failed to suggest an association between the Arg194Trp polymorphism and susceptibility of TC. However, in the subgroup analyses by ethnicity, the OR was 0.82 (C allele vs. T allele, 95% CI 0.68-0.98; P = 0.24 for heterogeneity) among the Chinese population. Nevertheless, no significant differences were observed in the Caucasian population in any genetic model. CONCLUSION: This study suggested that the C allele of XRCC1 had an 18% significantly decreased risk of TC in Chinese, and there were no significant associations among Caucasians under all genetic models.

20.
Zhonghua Yi Xue Za Zhi ; 99(45): 3587-3591, 2019 Dec 03.
Artigo em Chinês | MEDLINE | ID: mdl-31826576

RESUMO

Objective: To summarize the clinical characteristics of cardiomyopathy complicated with ventricular thrombosis. Methods: The clinical data of inpatients suffered from cardiomyopathy complicated with ventricular thrombosis in Fuwai Hospital between January 2015 and May 2019 were analyzed retrospectively. Results: A total of 125 cases were reviewed, and 24.8% were female. Dilated cardiomyopathy was the most common disease (62.4%), followed by arrhythmogenic right ventricular cardiomyopathy (ARVC) (13.6%) and hypertrophic cardiomyopathy (11.2%). There were 74.4% thrombosis in left ventricle, 12.8% in right ventricle and 12.8% in biventricle. The proportions of right ventricle thrombosis were higher in ARVC than in other cardiomyopathies (52.9% vs 6.5%, P<0.01). The majority suffered from cardiac function New York Heart Association (NYHA) Class Ⅲ (45.6%) and class Ⅳ (39.2%). The ratio of NYHA Class Ⅳ was higher in female patients than in male ones (25.8% vs 10.6%, P<0.05). In lab detection, positive results of D-Dimer and N terminal-pro B type natriuretic peptide (NT-proBNP) accounted for 72.8% and 97.6%, respectively. There were 2.5% patients died in the hospital or discharged because of the worsening of illness, the chances were higher in female than male patients (9.7% vs 0, P<0.01). Among these patients, one succumbed to massive ischemic stroke caused by ventricular thrombus detachment under standard anticoagulation therapy. Conclusions: Dilated cardiomyopathy is the most common cardiomyopathy complicated with ventricular thrombosis. The most common location of thrombosis is left ventricle. Right ventricle thrombosis is more common in ARVC. The majority suffer from moderate or severe cardiac dysfunction. Higer proportion of female patients suffer from anemia, severe condition and poor prognosis.


Assuntos
Displasia Arritmogênica Ventricular Direita , Cardiomiopatias , Cardiomiopatia Dilatada , Trombose , Feminino , Humanos , Masculino , Estudos Retrospectivos
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