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1.
Gastrointest Endosc ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31911077

RESUMO

BACKGROUND AND AIMS: Prediction models for esophageal squamous cell carcinoma are not common, and no model targeting a clinical population has previously been developed and validated. We aimed to develop a prediction model for estimating the risk of high-grade esophageal lesions for application in clinical settings and to validate the performance of this model in an external population. METHODS: The model was developed based on the results of endoscopic evaluation of 5624 outpatients in one hospital in a high-risk region in northern China and was validated using 5765 outpatients who had undergone endoscopy in another hospital in a non-high-risk region in southern China. Predictors were selected with unconditional logistic regression analysis. The Akaike information criterion was used to determine the final structure of the model. Discrimination was estimated using the area under the receiver operating characteristic curve (AUC). Calibration was assessed using a calibration plot with an intercept and slope. RESULTS: The final prediction model contained 5 variables, including age, smoking, body mass index, dysphagia, and retrosternal pain. This model generated an AUC of 0.871 (95% confidence interval, 0.842-0.946) in the development set, with an AUC of 0.862 after bootstrapping. The 5-variable model was superior to a single age model. In the validation population, the AUC was 0.843 (95% confidence interval, 0.793-0.894). This model successfully stratified the clinical population into 3 risk groups and showed high ability for identifying concentrated groups of cases. CONCLUSIONS: Our model for esophageal high-grade lesions has a high predictive value. It has the potential for application in clinical opportunistic screening to aid decision making for both health care professionals and individuals.

2.
Talanta ; 210: 120596, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31987206

RESUMO

A zwitterionic three-dimensional (3D) metal-organic framework (MOF) of {[Cu(Cdcbp)(bipy)]·4H2O}n (1) has been synthesized and characterized (H3CdcbpBr = 3-carboxyl-(3,5-dicarboxybenzyl)-pyridinium bromide; bipy = 4,4'-bipyridine). MOF 1 exhibits a variety of structural traits, such as ligand conjugated, positively charged pyridinium center, and Cu(II) cations that collectively enable its efficient hybridization with the flexible, negatively charged, single-stranded, and thymine-rich (T-rich) DNA. The T-rich DNA is labeled with carboxyfluorescein (FAM) fluorescent probe (characterized as P-DNA), but the resultant MOF 1 - P-DNA hybrid (characterized as P-DNA@1) is non-emissive (off-state) because of the fluorescent quenching by MOF 1. The P-DNA@1 hybrid functions as an effective and selective sensor for Hg2+ due to the formation of rigid hairpin-like T-Hg2+-T double-stranded DNA (ds-DNA@Hg2+) which is subsequently ejected by MOF 1, triggering a recovery of the P-DNA fluorescence (on-state). Subsequent addition of biothiols further sequestrates Hg2+ from the ds-DNA@Hg2+ duplex driven by the stronger Hg-S coordination, thus release the P-DNA and, in turn, resorbed by MOF 1 to regain the initial hybrid (off-state). P-DNA@1 hybrid thus detects Hg2+ and biothiols sequentially via a fluorescence "off-on-off" mechanism. The limits of detection (LOD) for Hg2+, biothiols, including cysteine (Cys), glutathione (GSH) and homocysteine (Hcy) are 3.0, 14.2, 15.1 and 8.0 nM, respectively, with the detection time of 60 min for Hg2+, and instantaneous detection for all the three biothiols. The detection mechanism is further confirmed by circular dichroism (CD), fluorescence anisotropy (FA), binding constant and molecular simulation. This sequential detection of Hg2+ and biothiols counter-proofs the presence of each other and may shed light to the occurrence of related diseases, such as neurodegenerative disorders of Parkinson's disease (PD), and Alzheimer's disease (AD).

3.
PeerJ ; 7: e8101, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31824761

RESUMO

Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer in the world, with a high degree of malignancy and recurrence. The influence of the ceRNA network in tumor on the biological function of liver cancer is very important, It has been reported that many lncRNA play a key role in liver cancer development. In our study, integrated data analysis revealed potential eight novel lncRNA biomarkers in hepatocellular carcinoma. Methods: Transcriptome data and clinical data were downloaded from the The Cancer Genome Atlas (TCGA) data portal. Weighted gene co-expression network analysis was performed to identify the expression pattern of genes in liver cancer. Then, the ceRNA network was constructed using transcriptome data. Results: The integrated analysis of miRNA and RNAseq in the database show eight novel lncRNAs that may be involved in important biological pathways, including TNM and disease development in liver cancer. We performed function enrichment analysis of mRNAs affected by these lncRNAs. Conclusions: By identifying the ceRNA network and the lncRNAs that affect liver cancer, we showed that eight novel lncRNAs play an important role in the development and progress of liver cancer.

4.
J Cancer ; 10(26): 6526-6534, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31777582

RESUMO

Aim: To explore gene expression profiling in hepatocellular carcinoma (HCC) cells exposed to swertiamarin. Methods: Cell viability, apoptosis and invasion were examined in HepG2 cells after swertiamarin treatment. Tumor growth of SK-Hep-1 cells xenografted in nude mice was monitored after swertiamarin treatment. Total RNA was isolated from HepG2 cells treated with swertiamarin for microarray analysis. The data of microarray were analyzed by bioinformatics. Results: Swertiamarin treatment decreased the viability and invasion while increased the apoptosis of HepG2 cells, and significantly inhibited the growth of SK-Hep-1 cells xenografted in nude mice. Pathway and biological process analysis of differentially expressed genes (DEGs) in swertiamarin treated HepG2 cells showed that PI3k-Akt was the most significant regulated pathway. 47 targets of swertiamarin were predicted by CGBVS while 21 targets were predicted by 3NN. Notably, 8 targets were predicted as the targets of swertiamarin by both programs, including two prominent targets JUN and STAT3. A large range of DEGs induced by swertiamarin could be regulated by JUN and STAT3. Conclusion: Swertiamarin treatment led to significant changes in the expression of a variety of genes that modulate cell survival, cell cycle progression, apoptosis, and invasion. Moreover, most of these genes can be clustered into pathway networks such as PI3K, JUN, STAT3, which are predicted targets of swertiamarin. Further confirmation of these targets will reveal the anti-tumor mechanisms of swertiamarin and facilitate the development of swertiamarin as a novel agent for cancer prevention and treatment.

5.
Chin J Cancer Res ; 31(4): 699-706, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31564812

RESUMO

Objective: To evaluate the accuracy of identifying cancer patients by use of medical claims data in a health insurance system in China, and provide the basis for establishing the claims-based cancer surveillance system in China. Methods: We chose Hua County, Henan Province as the study site, and randomly selected 300 and 1,200 qualified inpatient electronic medical records (EMRs) as well as the New Rural Cooperative Medical Scheme (NCMS) claims records for cancer patients in Hua County People's Hospital (HCPH) and Anyang Cancer Hospital (ACH) in 2017. Diagnostic information for NCMS claims was evaluated on an individual level, and sensitivity and positive predictive value (PPV) were calculated taking the EMRs as the gold standard. Results: The sensitivity of NCMS was 95.2% (93.8%-96.3%) and 92.0% (88.3%-94.8%) in ACH and HCPH, respectively. The PPV of the NCMS was 97.8% (96.7%-98.5%) in ACH and 89.0% (84.9%-92.3%) in HCPH. Overall, the weighted and combined sensitivity and PPV of NCMS in Hua County was 93.1% and 92.1%, respectively. Significantly higher sensitivity and PPV in identifying patients with common cancers than non-common cancers were detected in HCPH and ACH separately (P<0.01). Conclusions: Identification of cancer patients by use of the NCMS is accurate on individual level, and it is therefore feasible to conduct claims-based cancer surveillance in areas not covered by cancer registries in China.

6.
Carcinogenesis ; 40(12): 1445-1451, 2019 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-31570939

RESUMO

The clonal evolution which drives esophageal squamous cell carcinoma (ESCC) from initiation in normal cell to primary carcinoma and metastases is poorly understood. In this study, multi-region whole-exome sequencing (WES) (284X) and whole-genome single nucleotide polymorphism genotyping were performed on a total of 109 samples of ESCC from 10 patients. This included 42 apparently normal samples of esophageal mucosa at increasing distances from the upper or lower boundaries of the primary tumor to the surgical margins of resection, 43 spatially separated tissue samples within primary tumor and 24 regional lymph node metastases. Phylogenetic analysis was performed to reconstruct ancestor-descendant relationships of clones and the clonal composition of multi-region samples. Mutations of cancer-related genes were validated by deep targeted sequencing (1,168X). Both inter- and intra-tumoral genetic heterogeneity were obvious across multi-region samples among ESCC patients. Clones varying in number from one to seven were discovered within each regional tumor or metastatic sample. Phylogenetic analysis demonstrated complex clonal evolution patterns. Regional lymph node metastases had characteristics of early initiation and polyclonal spreading, and could be derived from carcinoma in situ (CIS) directly. TP53 was the only gene harboring non-silent mutations identified across all multi-region tumor samples of all ten patients. Mutations of TP53 were also found in histologically normal mucosa in sites away from primary tumor.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31518715

RESUMO

BACKGROUND & AIMS: Chromoendoscopy with iodine staining is used to identify esophageal squamous dysplasia and esophageal squamous cell carcinomas (ESCCs)-absence of staining indicates suspicious regions of dysplasia. However, screening detects precancerous lesions (mild and moderate dysplasia) that do not require immediate treatment; it is a challenge to which lesions are at risk for progression. We investigated the association between absence of iodine staining at chromoendoscopy screening and lesion progression using 6 years of follow-up data from a population-based randomized controlled trial in China. We then constructed and validated a model to calculate risk of progression to severe dysplasia, carcinoma in situ, or ESCC. METHODS: We collected data from 1468 participants (45-69 years old) who were either negative for iodine staining at a baseline chromoendoscopy or found to have mild or moderate dysplasia in histologic analysis of biopsies in the Endoscopic Screening for Esophageal Cancer study in China, from January 2012 through September 2016; 788 of these participants were re-examined by endoscopy after a median interval of 4.2 years (development cohort). We investigated the association between absence of iodine staining and progression of esophageal lesions using Cox prediction models, considering corresponding baseline pathology findings and patient answers to a comprehensive questionnaire. Patients who did not receive a follow-up examination (n = 680) was used as the validation cohort; outcome events in these patients were identified by annual door to door active interviews or linkage with local electronic registry data. The primary outcome was incident esophageal severe dysplasia, carcinoma in situ, or ESCC. RESULTS: In the development cohort, 11 lesions that did not stain with iodine but were classified as not dysplastic in the histology analysis were found to be severe dysplasia, carcinoma in situ, or ESCC at the follow-up evaluation. These lesions accounted for 39.3% of all progressed lesions (n = 28). In the validation cohort, 6 patients with lesions did not stain with iodine but were classified as not dysplastic by histology had a later diagnosis of ESCC, determined from medical records; these patients accounted for 50.0% of all patients with lesion progression (n = 12) until the closing date of this study. We developed a model based on patient age, body mass index, pathology findings, and baseline iodine staining to calculate risk for severe dysplasia, carcinoma in situ, or ESCC. It identified patients for severe dysplasia, carcinoma in situ, or ESCC in the development set with an area under the curve of 0.868 (95% CI, 0.817-0.920) and in the validation set with an area under the curve of 0.850 (95% CI, 0.748-0.952). Almost no cases would be missed if subjects determined to be high or intermediate-high risk subjects by the model were included in surveillance. CONCLUSIONS: Absence of iodine staining at baseline chromoendoscopy identifies esophageal lesions at risk of progression with a high level of sensitivity. A model that combines results of iodine chromoendoscopy with other patient features identifies patients at risk of lesion progression with greater accuracy than histologic analysis of baseline biopsies.

8.
Biomed Res Int ; 2019: 1050285, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31380412

RESUMO

Background: Th17/Treg balance skews towards Th17 in ITP patient. IRF4 has been highlighted for its close relationship to the immunosuppressive function of Treg cells and the IL-17 synthesis in CD4+ T cells. This study was aimed at examining the effects of IRF4 to the Th17/Treg cells in patients with ITP. Methods: Treg and Teff cells were isolated from PBMCs of newly diagnosed ITP patients. The percentages of CD4+CD25hiFoxp3+Treg cells and the CD3+CD4+IL-17+Th17 cells were detected by flow cytometry. After being cultured, the supernatants of Tregs were collected for IL-10 concentration test. The IRF4 levels of Tregs were measured. Teffs were cultured alone or with Tregs for 24 hours. Then the supernatants were collected for IL-17 concentration test. The binding intensity of IRF4 to the gene IL-10 in Treg cells was detected by ChIP-qPCR. Metabolic assays for Teffs and Tregs were performed with Agilent Seahorse XF96 Analyzer. Results: The secretion of IL-10 by Tregs was decreased in ITP patients. The intensity of IRF4 binding to IL-10 DNA of Tregs in patients was higher than that of normal controls and Teffs in ITP patients. The expressions of IRF4 of Tregs in ITP patients were remarkably lower than that of healthy controls. The percentage of Th17 cells in healthy controls was significantly increased after IRF4 mRNA silencing. Abnormal metabolism of Treg and Teff cells was found in ITP patients. Conclusion: The skewed ratio of Th17/Treg cells and dysfunction of Treg cells in newly diagnosed ITP patients was at least partly caused by IRF4 dysfunction. The underlying mechanism might be the impact of IRF4 on the metabolism of Treg and Teff cells.


Assuntos
Fatores Reguladores de Interferon/genética , Interleucina-10/genética , Púrpura Trombocitopênica Idiopática/genética , Linfócitos T Reguladores/imunologia , Adulto , Idoso , Linfócitos T CD4-Positivos/imunologia , Feminino , Regulação da Expressão Gênica , Humanos , Imunossupressão/métodos , Fatores Reguladores de Interferon/imunologia , Masculino , Pessoa de Meia-Idade , Ligação Proteica/imunologia , Púrpura Trombocitopênica Idiopática/imunologia , Púrpura Trombocitopênica Idiopática/patologia , Linfócitos T Reguladores/metabolismo , Células Th17/imunologia , Células Th17/metabolismo
9.
J Immunother Cancer ; 7(1): 232, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462302

RESUMO

BACKGROUND: T cell receptor-engineered T cells (TCR-Ts) therapy is a promising cancer treatment strategy. Nowadays, most studies focused on identification of high-avidity T cell receptors (TCRs) directed against neoantigens derived from somatic mutations. However, few neoantigens per patient could induce immune response in epithelial cancer and additionally many tumor-specific antigens could be derived from noncoding region. Autologous tumor cells (ATCs) could be unbiased stimulators in activating and enriching tumor-reactive T cells. However, it's unknown if T cells engineered to express TCRs isolated from tumor-reactive T cells enriched by ATCs have strong antitumor response. METHODS: In this study, multiple TIL fragments obtained from a patient with esophageal squamous cell carcinoma (ESCC) were screened for specific recognition of ATCs. Tumor-reactive TILs were enriched by in vitro repeated stimulation of ATCs and isolated based on CD137 upregulation. Subsequently, tumor-reactive TCR was obtained by single-cell RT-PCR analysis and was introduced into peripheral blood lymphocytes to generate TCR-Ts. RESULTS: We found that phenotype and effect function of TIL fragments derived from different tumor sites were spatially heterogeneous. Of four TIL fragments, only TIL-F1 could specifically identify ATCs. Subsequently, we isolated CD8+ CD137+ T cells from pre- and post-stimulated TIL-F1 co-cultured with ATCs, and identified their most dominant TCR. This TCR was introduced into PBLs to generate TCR-Ts, which specifically identified and killed ATCs in vivo and in vitro. CONCLUSION: This strategy provides the means to generate tumor-reactive TCR-Ts for ESCC, which is especially important for patients without prior knowledge of specific epitopes and might be applied for other cancers.

10.
J Theor Biol ; 480: 218-228, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31419443

RESUMO

Hepatocellular carcinoma (HCC) is a major type of primary liver cancer. HCC is influenced by sex and multiple metabolic abnormalities. The present study aimed to compare the overall metabolic changes between male and female HCC patients and identify key metabolic genes. Metabolic genes and pathways were identified based on analyses of publicly available data. Differential expression analysis, gene set enrichment analysis, survival analysis and transcriptional regulation analysis were employed to explore sex differences and identify key metabolic genes in HCC. The results suggested that female patients had more severe metabolic gene expression abnormalities and pathway deregulation than male patients. This study identified 9 key metabolic genes, and only upregulated ALDH1A2 independently increased overall survival risk in patients. Bioinformatic analyses suggest that upregulated GATA3 and TAL1 activate ALDH1A2 and then disrupt amino acid and carbohydrate metabolism, which may increase the risk of HCC. This study identified a novel contribution of upregulated ALDH1A2 to HCC. Future studies are needed to elucidate the potential metabolic mechanism of the role of ALDH1A2 in HCC.

11.
Thromb Res ; 181: 10-16, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31323447

RESUMO

BACKGROUND: Primary immune thrombocytopenia (ITP) is an autoimmune heterogeneous disorder of which Treg cells are numerically or functionally deficient. It is known that human FoxP3+CD4+ T cells were composed of 3 phenotypically and functionally distinct subpopulations (resting Treg, rTreg; activated Treg, aTreg; and non-suppressive Treg, n-sTreg). The current study was aimed to determine whether these Treg subtypes are altered in ITP patients and the related potential clinical applications. METHOD: Normal control volunteers and newly diagnosed ITP patients were enrolled in the study. The percentage of Treg cells' subtypes in peripheral blood was examined by flow cytometry before and after the glucocorticoid treatment. The IL-10 production by Treg subtypes was also examined. RESULTS: Treg cell subtypes of aTreg increased, rTreg decreased, and n-s Treg increased in newly diagnosed ITP patients' peripheral blood. The IL-10 production by respective Treg subtype didn't change after the treatment, and aTreg cells had the highest IL-10 yield. Patients who gained remission during follow-up had a higher aTreg cells' percentage than those who did not at the disease diagnosis. CONCLUSION: Tregs cell subtypes percentage was altered when ITP occurred. The increased aTreg cells at disease diagnosis might predict a better glucocorticoid treatment efficacy.


Assuntos
Glucocorticoides/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Linfócitos T Reguladores/imunologia , Adolescente , Adulto , Idoso , Feminino , Glucocorticoides/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Adulto Jovem
12.
J Clin Epidemiol ; 114: 141-149, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31226412

RESUMO

OBJECTIVES: The objective of this study was to establish an optimal population-level follow-up strategy for identifying incident cancers using health insurance reimbursement data in rural China. STUDY DESIGN AND SETTING: We compared active follow-up and passive linkage with claims data for identification of incident cancer cases. Claims data were derived from the New Rural Cooperative Medical Scheme (NCMS). Follow-up data from subject enrollment to December 31, 2016, regarding 33,948 subjects in a large-scale randomized controlled trial were used in this study. RESULTS: The overall sensitivity of passive linkage with NCMS claims data was significantly higher than that of active follow-up (95.6% vs. 54.9%, P < 0.001). Of 12 cases missed by the NCMS data set, seven were treated on an outpatient basis and there were therefore no records in the NCMS system, and five were diagnosed at primary (township-level) health facilities and excluded from the quality control process. Of the 123 cases missed by active follow-up, 54 were reported as negative, 69 were reported as positive but had inaccurate information regarding the site of cancer, or exceeded the 6-month limitation from the date of diagnosis. CONCLUSION: Passive linkage with NCMS claims data is an efficient approach for identifying incident cancers in areas without cancer registries in rural China.

13.
Ann Hematol ; 98(8): 1845-1854, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31154474

RESUMO

Primary immune thrombocytopenia is an autoimmune disease, characterized with decreased platelet and increased risk of bleeding. Recent studies have shown the reduction and dysfunction of regulatory T (Treg) cells in ITP patients. CD39 is highly expressed on the surface of Treg cells. It degrades ATP to AMP and CD73 dephosphorylates AMP into adenosine. Then adenosine binds with adenosine receptor and suppresses immune response by activating Treg cells and inhibiting the release of inflammatory cytokines from effector T (Teff) cells. Adenosine receptor has several subtypes and adenosine A2A receptor (A2AR) plays a crucial role especially within lymphocytes. The CD39+ Treg cells and the expression of A2AR showed abnormality in some autoimmune disease. But knowledge of CD39+ Treg cells and A2AR which are crucial in the adenosine immunosuppressive pathway is still limited in ITP. Thirty-one adult patients with newly diagnosed ITP were enrolled in this study. CD39 and A2AR expression was measured by flow cytometry and RT-PCR. The function of CD39 was reflected by the change of ATP concentration detected by CellTiter-Glo Luminescent Cell Viability Assay. CD39 expression within CD4+CD25+ Treg cells in ITP patients was decreased compared to normal controls. After high-dose dexamethasone therapy, response (R) group showed increased CD39 expression within Treg cells while non-response (NR) group did not show any difference in contrast to those before treatment. The expression of A2AR in CD4+CD25- Teff and CD4+CD25+ Treg cells was both lower in ITP patients than that of normal controls. After therapy, CD4+CD25- Teff cells had higher A2AR expression while CD4+CD25+ Treg cells did not show any difference in comparison to that before treatment. The enzymatic activity of CD39 was damaged in ITP patients and improved after high-dose dexamethasone therapy. In ITP, there was not only numerical decrease but also impaired enzymatic activity in CD39+ Treg cells. After high-dose dexamethasone treatment, these two defects could be reversed. Our results also suggested that ITP patients had reduced A2AR expression in both CD4+CD25+ Treg cells and CD4+CD25- Teff cells. CD4+CD25- Teff cells had increased A2AR expression after treatment.


Assuntos
Apirase/genética , Dexametasona/uso terapêutico , Imunossupressores/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Receptor A2A de Adenosina/genética , Linfócitos T Reguladores/efeitos dos fármacos , Adenosina/imunologia , Adenosina/metabolismo , Trifosfato de Adenosina/imunologia , Trifosfato de Adenosina/metabolismo , Adulto , Idoso , Apirase/imunologia , Estudos de Casos e Controles , Feminino , Expressão Gênica , Humanos , Imunofenotipagem , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/enzimologia , Púrpura Trombocitopênica Idiopática/genética , Púrpura Trombocitopênica Idiopática/imunologia , Receptor A2A de Adenosina/imunologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/enzimologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Reguladores/enzimologia , Linfócitos T Reguladores/imunologia
14.
Chin Med J (Engl) ; 132(13): 1516-1523, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31045906

RESUMO

BACKGROUND: The exact relationship between gastroesophageal reflux disease (GERD) and esophageal squamous cell cancer (ESCC) is far from clarification. The aim of this study was to investigate the epidemiology of GERD in a region with high prevalence of ESCC in China. METHODS: A population-based, cross-sectional study was conducted in a high ESCC prevalent area, Anyang, Henan, China. All subjects fulfilled questionnaires and underwent gastroendoscopy with routine esophageal biopsy. The subjects were divided into GERD subtypes (reflux esophagitis [RE] and non-erosive reflux disease [NERD]) and controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to examine risk factors for RE and NERD. RESULTS: A total of 2844 subjects were finally enrolled. The prevalence of GERD (RE + NERD) was 17.3%. Among them, 271 (9.53%) adults were diagnosed with RE. The prevalence of RE increased with age (7.09% in 45-50 years, 8.00% in 51-60 years, and 9.53% in 61-69 years, χ = 62.216, P < 0.001). Sixty-seven (2.36%) subjects were diagnosed with the silent RE. A total of 221 (7.77%) subjects were diagnosed with NERD. Frequent liquid food consumption (OR [95% CI]: 1.502 [1.076-2.095]) was independent risk factor for RE as well as age, male gender, high body mass index (BMI), ever smoking. Age was independent risk factor for NERD. For silent RE, age, male gender, and frequent liquid food consumption were risk factors. CONCLUSIONS: In the population with high prevalence of ESCC, a high prevalence of GERD and inverted proportion of RE/NERD were presented. Age was an independent risk factor for GERD. The male gender, high BMI, smoking, and frequent liquid food consumption may be risk factors for RE but not for NERD.


Assuntos
Neoplasias Esofágicas/epidemiologia , Esofagite Péptica/epidemiologia , Refluxo Gastroesofágico/epidemiologia , Idoso , Índice de Massa Corporal , China/epidemiologia , Estudos Transversais , Comportamento Alimentar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Fatores de Risco , Inquéritos e Questionários
15.
J Inorg Biochem ; 197: 110690, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31075721

RESUMO

A one-dimensional (1D) metal-organic framework (MOF) of [Cu(Cdcbp)(H2O)2·2H2O]n (1, H3CdcbpBr = 3-carboxyl-(3,5-dicarboxybenzyl)-pyridinium bromide) has been synthesized and characterized. MOF 1 features a cationic Cu2+ center, conjugated tricarboxylate ligand bearing positively charged pyridinium and uncoordinated carboxylate groups within its skeleton. These features enable MOF 1 to tightly adsorb thymine rich (T-rich) single-stranded DNA (ss-DNA) probe labeled with carboxyfluorescein (FAM) (denote as P-DNA) through π-stacking, electrostatic interactions and/or hydrogen bonding to give a hybrid complex (denote as P-DNA@1), and quenches its fluorescence via a photo-induced electron transfer (PET) process. The formed P-DNA@1 hybrid can thus function as a sensing platform for the detection of Hg2+, driven by the formation of hairpin-like double-stranded DNA (ds-DNA@Hg2+) with a T-Hg-T coordination motif, and subsequently dissociated into the solution due to its more rigid nature than ss-DNA, leading to the recovery of FAM fluorescence. In the presence of biothiols, including cysteine (Cys), homocysteine (Hcy) and glutathione (GSH), the strong coordination interaction between Hg2+ and the mercapto function serves to sequestrate the Hg2+ from the ds-DNA@Hg2+ duplex. The released ss-DNA, in turn, are re-adsorbed by MOF 1, leading to the formation of the initial P-DNA@1 state with fluorescence quenching. As such, P-DNA@1 detects Hg2+ and biothiols Cys/Hcy/GSH in sequence with detection limits of (2.3 ±â€¯0.8) nM and (29.6 ±â€¯0.1) nM/(19.8 ±â€¯0.5) nM/(10.2 ±â€¯0.1) nM. The sensing process is efficient and selective with instantaneous response time. The detection mechanism was further validated by circular dichroism (CD), and simulation studies using Molecular Operating Environment (MOE) package.

16.
Dalton Trans ; 48(24): 8911-8919, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31143896

RESUMO

A water-stable three-dimensional (3D) metal-organic framework (MOF) of {[Tb(Cmdcp)(H2O)3]2(NO3)2·5H2O}n (1, H3CmdcpBr = N-carboxymethyl-(3,5-dicarboxyl)pyridinium bromide) has been synthesized and characterized. MOF 1 is highly emissive, giving rise to green luminescence that can be quenched by Fe3+ due to the partial overlap of its excitation spectrum with the absorption spectrum of Fe3+. The subsequent introduction of ascorbic acid (AA) leads to the reduction of Fe3+ into Fe2+, accompanied by the near-entire recovery of MOF 1 emission. The density functional theory (DFT) calculation results support the proposed mechanism. Such a sensing cycle is further transferable to urine and serum samples with a satisfactory near-quantitative recovery, highlighting its good potential in biologically relevant applications.

17.
J BUON ; 24(2): 754-762, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31128033

RESUMO

PURPOSE: To retrospectively evaluate the role of prophylactic radiotherapy (RT) and clinical prognostic factors for primary testicular diffuse large B-cell lymphomas (PT-DLBCL) patients in our cohort. METHODS: Thirty patients diagnosed with PT-DLBCL between January 2007 and June 2017 were included in our study. Data came from electronic records and a histopathology electronic database. R and SPSS 23.00 were used for statistical analysis based on actual needs. RESULTS: Median age at diagnosis of PT-DLBCL was 60 years (28-82). At the time of analysis, 6 patients (20.0%) suffered disease progression. The estimated 5-year risk of recurrence after treatment was 24.7%. In multivariate analysis, international prognostic index (IPI) was identified as the only independent prognostic factor for overall survival (OS) (p=0.025, HR 1.675, 95%CI: 1.065-2.634) and progression-free survival (PFS) (p=0.037, HR 1.669, 95%CI: 1.032-2.700). No correlation was established between prophylactic RT and superior OS or PFS, respectively (p=0.745, p=0.194). No significant correlation was established in either group between RT and OS (Low-risk: p=0.848; High-risk group: p=0.433) or PFS (Low-risk: p=0.170; High-risk: Fig 4H, p=0.871). CONCLUSIONS: Chinese PT-DLBCL patients had an earlier age of onset and the number of advanced stage patients occupied a larger proportion. Also, the effect of prophylactic RT was not as good as expected.


Assuntos
Linfoma Difuso de Grandes Células B/radioterapia , Recidiva Local de Neoplasia/radioterapia , Prognóstico , Neoplasias Testiculares/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Criança , Ciclofosfamida/administração & dosagem , Progressão da Doença , Doxorrubicina/administração & dosagem , Feminino , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Prednisona/administração & dosagem , Intervalo Livre de Progressão , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/patologia , Neoplasias Testiculares/cirurgia , Vincristina/administração & dosagem
18.
Artif Cells Nanomed Biotechnol ; 47(1): 1938-1946, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31099261

RESUMO

Bionanotechnology has pivotal role in the development of a novel therapy, applications of gold nanoparticles (AuNPs) in the treatment of cancer. In this study, we found that therapeutics, pharmaceutics and diagnostic effectiveness of photosynthesized Catharanthus roseus (CR) AuNPs induces mitochondrial-mediated apoptotic signalling pathways via reactive oxygen species (ROS) induced cytotoxicity in cervical cancer cell line (HeLa) by in vitro model. The present examinations were for the most part centred around the gold chloride and photosynthesis AuNPs from the fluid leaf concentrate of CR and their harmful impacts on HeLa cell lines. The synthesized AuNPs were characterized using numerous biophysical analyses such as UV-vis, DLS, EDX, HR-TEM, SAED, FTIR and AFM. The synthesized AuNPs in the particle size range of 25-35 nm was confirmed by HR-TEM. The element gold and the crystalline nature of AuNPs were finalized using EDX, respectively. Anticancer potential of CR-AuNPs was studied using HeLa cells and the cytotoxic mechanism has been evaluated using MTT, mitochondrial-mediated apoptotic pathway through AO/EtBr staining assay, pro-apoptotic (Bax), anti-apoptotic (Bcl-2 and Bid) protein expression western blotting analysis and caspases activity using ELISA analysis. In in vitro study, the IC50 of HeLa cells was found to be 5 µg/ml confirmed using MTT assay. The present data revealed that drug delivery vehicles developed on CR-AuNPs nanocomplexes might include extensive purpose in human cancer diagnosis and treatment.


Assuntos
Caspase 3/metabolismo , Caspase 9/metabolismo , Catharanthus/química , Ouro/química , Ouro/farmacologia , Nanopartículas Metálicas/química , Nanotecnologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Feminino , Química Verde , Células HeLa , Humanos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Fotossíntese , Extratos Vegetais/química , Folhas de Planta/química , Espécies Reativas de Oxigênio/metabolismo , Neoplasias do Colo do Útero/patologia
19.
Artif Cells Nanomed Biotechnol ; 47(1): 1610-1616, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31072209

RESUMO

Nanotechnology has been materialized as a proficient technology for the development of anticancer nanoparticles all the way through an environment-friendly approach. Conventionally, nanoparticles have been assembled by dissimilar methods, but regrettably rely on the negative impact on the natural environment. Amalgamation of nanoparticles by means of plant extract is alternate conservative methods. In the present study, we equipped gold nanoparticles (AuNPs) from Strychni semen; displayed as a less toxic and environment-friendly. Integration of AuNPs was famed by UV-absorbance which displays peak values. Moreover, high-resolution transmission electron microscopy (HR-TEM), energy dispersive X-ray analysis (EDX) and atomic force microscopy (AFM) substantiate the shape of the AuNPs in the combined materials. FTIR results exhibit the active molecules positioned in the flat surface of the AuNPs. Similarly, the anticancer effectiveness of AuNPs is considered in KMCH-1 cells. Also, AuNPs successfully aggravate cytotoxicity and apoptosis by conjugating apoptotic gene expressions in KMCH-1 cells. Eventually, our results confirm the synthesis of AuNPs from Strychni Semen shows anticancer effects with environment-friendly manner.


Assuntos
Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Ouro/química , Ouro/farmacologia , Nanopartículas Metálicas/química , Extratos Vegetais/química , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Química Verde , Humanos , Tamanho da Partícula , Espécies Reativas de Oxigênio/metabolismo
20.
Pharmacoeconomics ; 37(6): 819-827, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30809788

RESUMO

BACKGROUND AND OBJECTIVE: Population-level endoscopic screening for esophageal cancer has been conducted in China for years. In this study, we aim to provide an updated and precise cost estimation for esophageal cancer screening based on a randomized controlled trial in a high-risk area in China. METHODS: We estimated the cost of esophageal cancer screening with chromoendoscopy using a micro-costing approach based on primary data of the ESECC (Endoscopic Screening for Esophageal Cancer in China) randomized controlled trial (NCT01688908) from a health sector perspective. Unit costs and quantities of resources were collected to obtain annual screening costs. The screening project was then theoretically expanded to a 10-year period to explore long-term trends of costs. Costs were adjusted to US dollars for the year 2018. RESULTS: In the ESECC trial, screening cost per endoscopy with a valid pathologic diagnosis was $196, accounting for 3.82% of the gross domestic product per capita in Hua County, and the costs for detecting one esophageal cancer and one early-stage esophageal cancer were $26,347 and $37,687, respectively. In conventional screening in which protocol-driven costs were excluded, costs as above were $134, $18,074, and $25,853. The cost for detecting one gastric cardia cancer or stomach cancer was nine times higher than detecting one esophageal cancer owing to low prevalences of the two cancers. In a simulated 10-year screening project, annual cost decreased notably over time. CONCLUSIONS: Despite the relatively low absolute cost, population-level endoscopic screening will still be a heavy burden on local government considering the socioeconomic conditions. Long-lasting programs would be less costly and population-level screening would make little sense in non-high-risk regions.

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