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OBJECTIVE: This study aims to comprehensively verify the efficacy of Buyang Huanwu Decoction in improving cognitive function in patients with diabetes. METHODS: Patients clinically diagnosed with mild cognitive impairment (MCI) assigned to either the placebo group or the Buyang Huanwu Decoction group. After strict screening and exclusions, a total of 156 participants completed the clinical trial, with 76 in the placebo group and 80 in the Buyang Huanwu Decoction group. RESULTS: After treatment, Buyang Huanwu Decoction group showed higher Mini-Mental State Examination and Montreal Cognitive Assessment scores compared to placebo (p < 0.05). Memory and Executive Screening, Boston Naming Test, and Animal Fluency Test scores were also higher in the treatment group (p < 0.05). No significant differences were found in DST and CDT scores (p > 0.05). Trail Making Test scores were lower in the treatment group (p < 0.05). No significant difference was observed between the two groups in terms of complications (p > 0.05). CONCLUSION: Patients receiving Buyang Huanwu Decoction treatment demonstrated improvement in cognitive function, showing positive effects and providing preliminary evidence for the role of Buyang Huanwu Decoction in improving cognitive function in patients with diabetes. This suggests its potential for clinical application and further promotion.
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BACKGROUND: Continuous glucose monitoring (CGM)-derived time in range (TIR) is closely associated with micro- and macrovascular complications in type 2 diabetes mellitus (T2DM). This study was performed to investigate the relationship between key CGM-derived metrics and specific cognitive domains in patients with T2DM. METHODS: Outpatients with T2DM who were otherwise healthy were recruited for this study. A battery of neuropsychological tests was performed to evaluate cognitive function, including memory, executive functioning, visuospatial ability, attention, and language. Participants wore a blinded flash continuous glucose monitoring (FGM) system for 72 h. The key FGM-derived metrics were calculated, including TIR, time below range (TBR), time above range (TAR), glucose coefficient of variation (CV), and mean amplitude of glycemic excursions (MAGE). Furthermore, the glycemia risk index (GRI) was also calculated by the GRI formula. Binary logistic regression was used to assess risk factors for TBR, and we further analysed the associations between neuropsychological test results and key FGM-derived metrics with multiple linear regressions. RESULTS: A total of 96 outpatients with T2DM were recruited for this study, with 45.8% experiencing hypoglycemia (TBR< 3.9 mmol/L). Spearman analysis results revealed that a higher TBR< 3.9 mmol/L was correlated with worse performance on the Trail Making Test A (TMTA), Clock Drawing Test (CDT), and cued recall scores (P < 0.05). Logistic regression analysis results indicated that the TMTA (OR = 1.010, P = 0.036) and CDT (OR = 0.429, P = 0.016) scores were significant factors influencing the occurrence of TBR< 3.9 mmol/L. Multiple linear regressions further demonstrated that TBR< 3.9 mmol/L (ß = -0.214, P = 0.033), TAR> 13.9 mmol/L (ß = -0.216, P = 0.030) and TAR10.1-13.9 mmol/L (ß = 0.206, P = 0.042) were significantly correlated with cued recall scores after adjusting for confounding factors. However, TIR, GRI, CV and MAGE showed no significant correlation with the results of neuropsychological tests (P > 0.05). CONCLUSIONS: A higher TBR< 3.9 mmol/L and TAR> 13.9 mmol/L were associated with worse cognitive functions (memory, visuospatial ability, and executive functioning). Conversely, a higher TAR of 10.1-13.9 mmol/L was associated with better memory performance in memory tasks.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicações , Automonitorização da Glicemia , Glicemia , Pacientes Ambulatoriais , Cognição , GlucoseRESUMO
Intestinal barrier injury is a common complication of severe acute pancreatitis (SAP), which is often accompanied by intestinal mucosal barrier injury and results in serious consequences. However, the exact mechanism remains unclear. We aimed to investigate whether angiotensin II type 1 receptor (AT1)-mediated oxidative stress is involved in SAP intestinal barrier injury and assessed the effects of inhibiting this pathway. The SAP model was established by retrograde bile duct injection of sodium taurocholate (5%). The rats were divided into three groups: the control group (SO), the SAP group (SAP), and the azilsartan intervention group (SAP + AZL). Serum amylase, lipase, and other indexes were measured to evaluate SAP severity in each group. Histopathological changes in the pancreas and intestine were evaluated by HE staining. The oxidative stress of intestinal epithelial cells was detected by superoxide dismutase and glutathione. We also detected the expression and distribution of intestinal barrier-related proteins. The results showed that the serum indexes, the severity of tissue damage, and the level of oxidative stress in the SAP + AZL group were significantly lower than in the SAP group. Our study provided hitherto undocumented evidence of AT1 expression in the intestinal mucosa, confirming that AT1-mediated oxidative stress is involved in SAP intestinal mucosal injury, and inhibiting this pathway could effectively reduce intestinal mucosal oxidative stress injury, providing a new and effective target for the treatment of SAP intestinal barrier injury.
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Estresse Oxidativo , Pancreatite , Receptor Tipo 1 de Angiotensina , Animais , Ratos , Doença Aguda , Mucosa Intestinal/metabolismo , Pancreatite/induzido quimicamente , Pancreatite/tratamento farmacológico , Ratos Sprague-Dawley , Receptor Tipo 1 de Angiotensina/genéticaRESUMO
AIMS/INTRODUCTION: This study was carried out to investigate the relationship of stressful life events (SLEs) with the risk of cognitive impairment in patients with type 2 diabetes mellitus. MATERIALS AND METHODS: A total of 316 patients with type 2 diabetes mellitus aged >45 years were recruited in this study, and data on demographics, medical history, lifestyle characteristics and SLEs were collected. The cognitive status of patients was evaluated with a battery of cognitive function scales. Logistic regression analyses were carried out to evaluate the risk and protective factors for mild cognitive impairment (MCI). RESULTS: Participants, including 217 type 2 diabetes mellitus patients with MCI and 99 patients without MCI, were enrolled in the current study. Among the SLEs, the death of an offspring or parent (odds ratio [OR] 1.994, 95% confidence interval [CI] 1.017-3.908) was a risk factor for MCI after adjustment for age and education level. In the subgroup of participants aged <60 years, the death of an offspring or parent (OR 2.731, 95% CI 1.119-6.665) and financial difficulty (OR 22.205, 95% CI 4.365-112.966) were risk factors for the development of MCI, whereas high working pressure (OR 0.154, 95% CI 0.048-0.495) and career changes (OR 0.324, 95% CI 0.124-0.847) were protective factors for MCI. CONCLUSIONS: These data suggested that SLEs were associated with cognitive function in patients with type 2 diabetes mellitus. Adverse life events, such as the death of an offspring or parent, were risk factors for cognitive impairment, whereas high work pressure in middle-aged people was a protective factor against cognitive impairment.
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Disfunção Cognitiva , Diabetes Mellitus Tipo 2 , Pessoa de Meia-Idade , Humanos , Diabetes Mellitus Tipo 2/complicações , Disfunção Cognitiva/complicações , Disfunção Cognitiva/epidemiologia , Fatores de Risco , Estilo de VidaRESUMO
Background: Acute kidney injury (AKI) is a common complication in patients with severe acute pancreatitis (SAP). Caspase-11-mediated pyroptosis is essential for the progression of multiple diseases, but its role in SAP-induced AKI remains unknown.Aims: This research investigated whether caspase-11-mediated pyroptosis is involved in SAP-induced AKI and whether inhibiting caspase-11-mediated pyroptosis improves SAP-induced AKI.Methods: A rat model of SAP with AKI was established by slowly injecting 5% sodium taurocholate into the biliopancreatic duct, then wedelolactone (25 or 50 mg/kg), an inhibitor of caspase-11, was injected through the intra-peritoneum 1 and 6 h after SAP induction. Serum biochemical indexes, including serum amylase, lipase, interleukin (IL)-6, blood urea nitrogen (BUN), tumor necrosis factor (TNF)-α, and creatinine (Cr) in rats, were evaluated using biochemical test kits. Caspase-11 and gasdermin D (GSDMD) expression in the kidney tissues was evaluated by western blotting and immunohistochemical staining. IL-1ß and IL-18 levels in kidney tissues were detected by ELISA kits. Furthermore, histopathological alterations of pancreas and kidney were assessed by H&E staining.Results: The serum biochemical indexes and pyroptosis-related proteins in kidney tissues were significantly increased after SAP induction. Furthermore, wedelolactone decreased the expression of pyroptosis-linked proteins in kidney tissues, reduced serum lipase, amylase, IL-6, TNF-α, BUN, and Cr, and ameliorated the renal and pancreatic histological damage in SAP rats.Conclusion: Caspase-11-mediated pyroptosis contributes to SAP-induced AKI, and targeting caspase-11-mediated pyroptosis might be a novel treatment strategy for SAP-induced AKI.
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Injúria Renal Aguda , Pancreatite , Ratos , Animais , Pancreatite/complicações , Pancreatite/tratamento farmacológico , Piroptose , Caspases/efeitos adversos , Doença Aguda , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/metabolismo , Creatinina , Fator de Necrose Tumoral alfa , Amilases , Interleucina-6 , LipaseRESUMO
Increasing evidence from epidemiological studies indicate that Alzheimer's disease (AD) has a negative relationship with the incidence of cancers. Whether the Alzheimer's genetic risk factor, named as fermitin family homolog-2 (FERMT2), plays a pivotal part in the progressive process of colorectal carcinoma (CRC) yet remains unclear. This study revealed that FERMT2 was upregulated in CRC tissues which predicted an unfavorable outcome of CRC using the PrognoScan web tool. FERMT2 was co-expressed with a variety of genes have been linked with CRC occurrence and implicated in the infiltration of immune cell in CRC tissues. Overexpressing FERMT2 promoted CRC progression with upregulation of Wnt/ß-catenin signaling. Knockdown of FERMT2 suppressed the cell multiplication, colony formation rate, migration and invasion, along with the epithelial to mesenchymal transition (EMT) with downregulation Wnt/ß-catenin proteins in cells of CRC, while overexpressing ß-catenin reversed the inhibitory effects of silencing FERMT2 on the migration or invasion of CRC cells. Furthermore, Aß1-42 treated HT22 cells induced downregulation of FERMT2 and inhibited the migration, invasion and EMT in co-cultured CT26 cells through Wnt/ß-catenin signaling. Our results revealed that the downregulated FERMT2 gene during AD is prominently activated in CRC, which promotes its progression via Wnt/ß-catenin pathway.
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Doença de Alzheimer , Neoplasias Colorretais , Proteínas de Membrana , Via de Sinalização Wnt , Humanos , Doença de Alzheimer/genética , beta Catenina/genética , Neoplasias Colorretais/genética , Transição Epitelial-Mesenquimal/genética , Fatores de Risco , Proteínas de Membrana/genéticaRESUMO
OBJECTIVE: Diabetic encephalopathy (DE), a chronic complication of diabetes, is characterized by decline of cognitive function. The molecular mechanism of DE remains unclear. The purpose of this study is to evaluate the roles of advanced glycation end products (AGEs) in the pathogenesis of DE and investigate its underlying mechanisms in this process. METHODS: DE rats were developed by incorporating a high-fat diet and streptozotocin injection followed by the Morris Water Maze test. HT-22 cells were used to mimic the in vitro neuronal injuries of DE. Expression levels of long non-coding RNA H19, miR-15b and ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) mRNA in the hippocampus of DE rats or HT-22 cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The levels of BACE1 proteins were analyzed by western blotting or immunohistochemical staining. The contents of Aß1-42 in supernatant of the cell culture were analyzed by enzyme-linked immu-nosorbent assay (ELISA). The relationship between H19 or BACE1 and miR-15b was verified with dual-luciferase reporter assay. RESULTS: We found that the accumulation of Aß1-42 and the phosphorylation of Tau (Ser404) were increased in the hippocampus CA3 regionof DE rats. MiR-15b was downregulated while H19 and BACE1 were upregulated in the hippocampus CA3 regionof DE rats and AGEs-treated HT-22 cells. The expression of BACE1 protein was negatively regulated by miR-15b at the post-transcriptional level in HT-22 cells. In vivo, administration of miR-15b mimics by the intranasal delivery markedly decreased the BACE1 protein in hippocampal CA3 region and improved the cognitive decline in DE rats. Besides, the luciferase activity assay confirmed the binding site of miR-15b to both the 3'-untranslated region (3'-UTR) of BACE1 mRNA and H19. Then, miR-15b inhibitor reversed H19 knockdown-mediated decrease of Aß1-42 level in AGEs-treated HT-22 cells. CONCLUSION: These results suggested that AGEs induced Aß1-42 deposition andcognitive decline through H19/miR-15b/ BACE1 axis in DE.
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Encefalopatias , Disfunção Cognitiva , Diabetes Mellitus , MicroRNAs , RNA Longo não Codificante , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides , Animais , Ácido Aspártico Endopeptidases/metabolismo , Produtos Finais de Glicação Avançada , MicroRNAs/genética , MicroRNAs/metabolismo , Fragmentos de Peptídeos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RatosRESUMO
BACKGROUND: The interactions between environmental factors and genetic variants have been implicated in the pathogenesis of Alzheimer's disease (AD). The altered gut microbiota (GM) and vitamin D deficiency are closely associated with the higher risk of AD. OBJECTIVE: This study was performed to evaluate whether the crosstalk between GM and single nucleotide polymorphisms (SNPs) of vitamin D receptor (VDR) or vitamin D binding protein (VDBP) have a link with the risk of amnestic mild cognitive impairment (aMCI) in the Chinese elderly population. METHODS: A total of 171 aMCI patients and 261 cognitive normal controls (NC) were enrolled in this study. Six tag SNPs of VDR and VDBP were genotyped by PCR-RFLP. The serum levels of vitamin D, Aß1-42, and p-tau (181P) were determined by using of ELISA kits. The alterations in the GM were analyzed by full-length 16S ribosomal RNA (rRNA) gene sequencing. RESULTS: The frequencies of AG genotype and A allele of VDR rs1544410 in aMCI group were significantly higher than that in NC group (genotype: pâ=â0.002, allele: pâ=â0.003). Patients with aMCI showed an abnormal GM composition compared with NC group. Interestingly, significant differences in GM composition were found between aMCI and NC group among individuals with AG genotype, as well as between individuals with AG and GG genotype of VDR rs1544410 among patients with aMCI. CONCLUSION: These results implicated that the crosstalk between gut microflora and vitamin D receptor variants are associated with the risk of aMCI in Chinese elderly population.
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Doença de Alzheimer , Disfunção Cognitiva , Microbioma Gastrointestinal , Idoso , Doença de Alzheimer/genética , China , Disfunção Cognitiva/genética , Microbioma Gastrointestinal/genética , Humanos , Polimorfismo de Nucleotídeo Único/genética , Receptores de Calcitriol/genéticaRESUMO
BACKGROUND: miR-34c has been found to be implicated in the pathological process of Alzheimer's disease, diabetes, and its complications. OBJECTIVE: To investigate the underlying mechanisms of miR-34c in the pathogenesis of diabetic encephalopathy (DE). METHODS: Diabetes mellitus rats were developed by incorporating a high-fat diet and streptozotocin injection. Morris water maze test and novel object recognition test were used to assess the cognitive function of rats. Expression of miR-34c were detected by fluorescence in situ hybridization and qRT-PCR. Immunofluorescence and western blot were used to evaluate synaptotagmin 1 (SYT1) and AdipoR2 or other proteins. Golgi staining was performed to investigate dendritic spine density. RESULTS: The increased miR-34c induced by advanced glycation end-products (AGEs) was mediated by ROS-JNK-p53 pathway, but not ROS-Rb-E2F1 pathway, in hippocampus of DE rats or in HT-22 cells. miR-34c negatively regulated the expression of SYT1, but not AdipoR2, in hippocampal neurons. miR-34c inhibitor rescued the AGE-induced decrease in the density of dendritic spines in primary hippocampal neurons. Administration of AM34c by the intranasal delivery increased the hippocampus levels of SYT1 and ameliorated the cognitive function in DE rats. The serum levels of miR-34c were increased in patients with DE comparing with normal controls. CONCLUSION: These results demonstrated that AGE-induced oxidative stress mediated increase of miR-34c through ROS-JNK-p53 pathway, resulting in synaptic deficits and cognitive decline by targeting SYT1 in DE, and the miR-34c/SYT1 axis could be considered as a novel therapeutic target for DE patients.
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Doença de Alzheimer , Disfunção Cognitiva , Diabetes Mellitus , MicroRNAs , Animais , Disfunção Cognitiva/genética , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Hibridização in Situ Fluorescente , MicroRNAs/genética , MicroRNAs/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Sinaptotagmina I/genética , Sinaptotagmina I/metabolismo , Proteína Supressora de Tumor p53RESUMO
BACKGROUND: Mitochondrial dysfunction is an early feature of Alzheimer's disease (AD) and miR-195 is involved in mitochondrial disorder through targeting MFN-2 protein in hippocampal neurons of AD. OBJECTIVE: To clarify if administration of miR-195 inhibitor could enhance the memory deficits through improving hippocampal neuron mitochondrial dysfunction in SAMP8 mice. METHODS: The expression of miR-195 was detected by RT-qPCR in primary hippocampal neurons and HT-22 cells treated with Aß1-42. Morris water maze (MWM) was used to assess the learning and memory function in SAMP8 mice administrated with antagomir-195. Transmission electron microscopy was employed to determine the morphological changes of synapses and mitochondria of hippocampus in SAMP8 mice. Mitochondrial respiration was measured using a high-resolution oxygraph. RESULTS: The expression of miR-195 were upregulated in the primary hippocampal neurons and HT-22 cells induced by Aß1-42. Inhibition of miR-195 ameliorated the mitochondrial dysfunction in HT-22 cells induced by Aß1-42, including mitochondrial morphologic damages, mitochondrial membrane potential, respiration function, and ATP production. Administration of antagomir-195 by the third ventricle injection markedly ameliorated the cognitive function, postsynaptic density thickness, length of synaptic active area, mitochondrial aspect ratio, and area in hippocampus of SAMP8 mice. Finally, antagomir-195 was able to promote an increase in the activity of respiratory chain complex CI and II in SAMP8 mice. CONCLUSION: This study demonstrated that miR-195 inhibitor ameliorated the cognitive impairment of AD mice by improving mitochondrial structure damages and dysfunction in the hippocampal neurons, which provide an experimental basis for further exploring the treatment strategy of AD.
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Memória/efeitos dos fármacos , MicroRNAs/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Sinapses/efeitos dos fármacos , Doença de Alzheimer/metabolismo , Animais , Apoptose , Disfunção Cognitiva/metabolismo , Modelos Animais de Doenças , Feminino , GTP Fosfo-Hidrolases , Hipocampo/metabolismo , Masculino , Camundongos , Mitocôndrias/metabolismoRESUMO
BACKGROUND AND OBJECTIVE: Compared with tissue biopsy, liquid biopsy is the most preferable non-invasive promising method in personalized medicine, although it has many limitations in isolating circulating tumor cells (CTC). Lung cancer associated mortality is drastically increased due to a shortfall of early-stage detection, which remains a challenge. Herein, we aimed to detect lung cancer at an early-stage using CellCollector device. METHODS: 39,627 volunteers underwent low-dose computed tomography; 2508 cases with pulmonary nodules and 7080 with no pulmonary nodules were chosen. After follow-up, 24 patients were diagnosed with early-stage non-small cell lung cancer (NSCLC), and subjected to CTC detection using CellCollector, along with 72 healthy volunteers. Immunofluorescence staining for EpCAM/CKs and CD45 were performed for CTC validation. RESULTS: Fifteen out of twenty-four (stage I, n = 18; stage II, n = 6) early-stage lung cancer patients were found to be CTC-positive, whereas no CTC was found in the control group. Genetic mutation of TP53, ERBB2, PDGFRA, CFS1R and FGFR1 in the CTC revealed 71.6% of the mutation sites similar to the tumor tissues of 13 patients. Molecular characterization revealed higher expression of protein PD-LI in CTC (40%) as compared to tumor tissue (26.7%). Moreover, CTC clusters were detected in 40% of patients. CONCLUSION: CTC detection using the CellCollector in early-stage NSCLC had a relative high capture rate. Moreover, CTC analysis is a prospective setting for molecular diagnostic in cases when tumor tissue biopsy is not desirable.
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Alzheimer's disease (AD) and cancer have inverse relationship in many aspects. Some tumor suppressors, including miR-34c, are decreased in cancer but increased in AD. The upstream regulatory pathways and the downstream mechanisms of miR-34c in AD remain to be investigated. The expression of miR-34c was detected by RT-qPCR in oxidative stressed neurons, hippocampus of SAMP8 mice, or serum of patients with amnestic mild cognitive impairment (aMCI). Dual luciferase assay was performed to confirm the binding sites of miR-34c in its target mRNA. The Morris water maze (MWM) was used to evaluate learning and memory in SAMP8 mice administrated with miR-34c antagomir (AM34c). Golgi staining was used to evaluate the synaptic function and structure. The dramatically increased miR-34c was mediated by ROS-JNK-p53 pathway and negatively regulated synaptotagmin 1 (SYT1) expression by targeting the 3'-untranslated region (3'-UTR) of syt1 in AD. The expression of SYT1 protein was reduced by over expression of miR-34c in the HT-22 cells and vice versa. Administration of AM34c by the third ventricle injection or intranasal delivery markedly increased the brain levels of SYT1 and ameliorated the cognitive function in SAMP8 mice. The serum miR-34c was significantly increased in patients with aMCI and might be a predictive biomarker for diagnosis of aMCI. These results indicated that increased miR-34c mediated synaptic and memory deficits by targeting SYT1 through ROS-JNK-p53 pathway and the miR-34c/SYT1 pathway could be considered as a promising novel therapeutic target for patients with AD.
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Doença de Alzheimer/metabolismo , Disfunção Cognitiva/sangue , Sistema de Sinalização das MAP Quinases/genética , MicroRNAs/sangue , Espécies Reativas de Oxigênio/metabolismo , Sinapses/metabolismo , Sinaptotagmina I/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Regiões 3' não Traduzidas , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/genética , Animais , Antagomirs/farmacologia , Sítios de Ligação , Biomarcadores/sangue , Modelos Animais de Doenças , Feminino , Células HEK293 , Hipocampo/metabolismo , Humanos , Masculino , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Plasticidade Neuronal/genética , Neurônios/metabolismo , RNA Mensageiro/metabolismo , TransfecçãoRESUMO
Background: Urothelial carcinoma associated 1 (UCA1), a novel long noncoding RNA (lncRNA) which is first discovered in 2006 in human bladder cancer and has become a hot spot in recent years. UCA1 has been demonstrated correlated with clinical outcomes in various cancers. However, the results from each study are insufficient and not completely consistent. Therefore, we perform a systematic meta-analysis to evaluate the value for a feasible biomarker for metastasis and prognosis of cancer. Methods: Relevant English literatures were searched in PubMed, Cochrane Library, Web of science, Embase databases and Chinese literatures were searched in Chinese National Knowledge Infrastructure Wanfang from inception up to 17 April 2018. The pooled odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) using random/fixed-effect were used to identify the relationship between UCA1 and lymph node metastasis (LNM) or overall survival (OS) of cancer patients. Subgroup analysis and sensitivity analysis were performed. The current meta-analysis was performed using Review Manager 5.3 and Stata 12.0 software. Results: A total of 3411 patients from 38 studies were finally included. Patients who with high UCA1 expression suffered from an increased risk of LNM (OR = 2.50; 95% CI: 1.93-3.25). UCA1 was also significantly associated with OS (HR = 2.05; 95% CI: 1.77-2.38). Subgroup analyses across several different variables also showed the similar results in LNM and OS of cancer patients. Conclusion: High expression of UCA1 was linked with poor clinical outcome. UCA1 can serve as a potential molecular marker for metastasis and prognosis in different types of cancers.
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Biomarcadores Tumorais/genética , Metástase Linfática/genética , Neoplasias/genética , RNA Longo não Codificante/genética , Intervalo Livre de Doença , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Neoplasias/patologia , Prognóstico , Modelos de Riscos ProporcionaisRESUMO
The present study aimed to investigate the therapeutic effect of combined hyperbaric oxygen and radiation therapy for the treatment of single brain metastasis (SBM), as well as its influence on osteopontin (OPN) and matrix metalloproteinase-9 (MMP-9). A total of 86 patients with SBM were admitted to Hongqi Hospital from January 2013 to January 2016 and those included within the study were randomly divided into two groups. The control group was only treated with whole brain radiotherapy, while the observation group was treated with hyperbaric oxygenation combined with whole brain radiotherapy. OPN and MMP-9 expression was measured in each group by ELISA and the results prior to and following treatment were compared. The total effective rate (patients with complete remission, partial remission or stabilized lesions) in the observation group (95.3%) was significantly increased compared with the control group (67.4%). However, the OPN and MMP-9 protein levels observed in the observation group were significantly reduced compared with the control group (P<0.05). In addition, the quality of life and the incidence of adverse reactions in the observation group were significantly improved compared with the control group (P<0.05). For patients with SBM, hyperbaric oxygenation combined with radiotherapy may improve the efficiency of treatment and should be considered for further investigation and use within a clinical setting.
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The present meta-analysis aimed to systematically evaluates the metastasis, clinical stage, and prognostic value regarding the expression levels of PVT1 in various cancers. Relevant literatures were searched in PubMedãCochrane LibraryãWed of scienceãEmbase databasesãChinese National Knowledge Infrastructure and Wanfang from inception up to 22 August 2017. After data were extracted, a meta-analysis was performed using Review Manager 5.3 and Stata 12.0 software. The meta-analysis showed that high expression of PVT1 could predict more lymph node metastasis (LNM) (Odds ratio, OR = 2.83, 95% confidence interval, CI: 1.76-4.54, P < 0.0001), distant metastasis (DM) (OR = 3.60, 95% CI: 1.08-12.03, P = 0.04), advanced clinical stage (OR = 4.37, 95% CI: 3.45-5.54, P < 0.00001) and poor overall survival (Hazard ratio, HR = 2.08, 95% CI: 1.82-2.37, P < 0.00001)in cancer. Subgroup analysis in different systems also showed the same results, including respiratory systemãdigestive systemãurinary system and other systems, especially in respiratory system (LNM, OR = 4.57, 95% CI: 2.41-8.68, P < 0.00001; clinical stage, OR = 5.59, 95% CI: 3.59-8.71, P < 0.00001; OS, HR = 2.43, 95% CI: 1.98-2.99, P < 0.00001). These results suggest that PVT1 could serve as a novel biomarker for metastasis, clinical stage and poor prognosis in various tumors.
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Metástase Linfática/genética , Neoplasias/genética , Neoplasias/patologia , RNA Longo não Codificante/genética , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Humanos , Metástase Linfática/patologia , PrognósticoRESUMO
BACKGROUND: The association between fine particulate matter (PM2.5 ) and lung cancer (LC) mortality in China is limited. The Beijing-Tianjin-Hebei region is infamous for serious air pollution. Seven of the top 10 cities with the worst air quality are located in Hebei Province. Thus, we explored the effect of 10 years of PM2.5 on the LC mortality rate in Hebei Province. METHODS: We quantified associations between LC mortality and PM2.5 and estimated the LC mortality burden attributed to PM2.5 with predicted county level LC deaths in 2014. RESULTS: The 10-year PM2.5 LC mortality associations were non-linear, with thresholds of 63 µg/m3 overall, 69 µg/m3 for men, 68 µg/m3 for women, 66 µg/m3 for those aged 30-64 years, and 62 µg/m3 for those aged ≥ 65 years. The relative risks for these groups were 1.09 (95% confidence interval [CI] 1.08-1.10), 1.06 (95% CI 1.03-1.10), 1.20 (95% CI 1.10-1.26), 1.07 (95% CI 1.05-1.11), and 1.10 (95% CI: 1.07-1.13), respectively. There were 2525 (95% CI 2265-2780) LC deaths attributed to 10-year PM2.5 in 2014, at fractions of 8.3% (95% CI 7.4-9.1%) overall, 5.7% (95% CI 2.8-9.4%) for men, 16.7% (95% CI: 8.3-21.6%) for women, 6.5% (95% CI 4.7-10.3%) for those aged 30-64 years, and 9.1% (95% CI 6.4-11.5%) for those aged ≥ 65 years. CONCLUSION: Our results suggest that a reduction in the PM2.5 exposure levels below thresholds would prevent a substantial number of LC deaths in Hebei Province.
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Poluição do Ar/efeitos adversos , Neoplasias Pulmonares/mortalidade , Material Particulado/efeitos adversos , Adulto , Idoso , China/epidemiologia , Feminino , Humanos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
Cixian is one of the high-risk areas for upper gastrointestinal cancer in China and the world. From 2005, comprehensive population-based screening for upper gastrointestinal cancers has been conducted in Cixian. The aim of this study was to investigate population-based cancer survival from 2003 to 2013 and to explore the effect of screening on upper gastrointestinal cancer survival in Cixian. Observed survival was estimated using the life table method. The expected survival from the general population was calculated using all-cause mortality data from the population of Cixian with the EdererII method. Cixian cancer registry, with a total coverage of 6.88 million person years, recorded 19,628 cancer patients diagnosed during 2003-2013. In Cixian, from 2003 to 2013, there were 19,628 newly cancer cases and 13,984 cancer deaths, with an incidence rate of 285.37/100,000 and mortality rate of 203.31/100,000. The overall five-year relative cancer survival for patients diagnosed in Cixian in 2003-2013 was 22.53%. The relative survival for all cancers combined in Cixian had an overall upward trend from 2003 to 2013. Among upper gastrointestinal cancer in Cixian, the five-year relative survival for cardia gastric cancer was highest at 30.42%, followed by oesophageal cancer at 25.37% and noncardia gastric cancer at 18.93%. In 2013, the five-year relative survival for oesophageal cancer, cardia gastric cancer, and noncardia gastric cancer patients aged 45-69 years was 39.97% (95% CI: 34.52-45.43%), 51.74% (95% CI: 42.09-60.86%), and 37.43% (95% CI: 26.93-48.17%), respectively, the absolute values increasing 14.11%, 16.71%, and 14.92% compared with that in 2003. There is an increasing trend in overall survival for upper gastrointestinal cancer with early screening and treatment of cancer in Cixian.
Assuntos
Neoplasias/mortalidade , Fatores Etários , Idoso , China/epidemiologia , Feminino , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/mortalidade , História do Século XXI , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mortalidade , Neoplasias/epidemiologia , Neoplasias/história , Vigilância em Saúde Pública , Sistema de RegistrosRESUMO
Whether in the world or China, lung cancer is a malignant tumor which is harmful to human health. There were studies showed that lung cancer is tightly related to the environment factors and life style. The epidemiology study found that eating more fruits and vegetables can prevent lung cancer. Vegetables and fruits are rich in phytochemicals such as isothiocyanates, indoles, flavonoids and so on. These phytochemicals reduce the risk of lung cancer by modulating antitumor-related pathways such as inhibition of cell proliferation, induction of apoptosis, and the like. The aim of this review is to summarize the mechanisms of phytochemicals in vegetables and fruits in the pathogenesis and progression of lung cancer, so as to provide theoretical basis and direction for the prevention and treatment of lung cancer.
Assuntos
Anticarcinógenos/farmacologia , Frutas/química , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/prevenção & controle , Compostos Fitoquímicos/farmacologia , Verduras/química , Anticarcinógenos/química , Anticarcinógenos/uso terapêutico , Humanos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/uso terapêuticoRESUMO
To investigate the effects of Fritillariae Cirrhosae Bulbus on airway remodeling and matrix metalloproteinase-2(MMP-2), matrix metalloproteinase-9(MMP-9), tissue inhibitor-1 of metalloproteinase(TIMP-1) of a murine asthma model, and explore its mechanism in treatment of asthma. BALB/C murines were randomly divided into the normal group, model group, high dose group, low dose group, and positive control group. Except for the normal group, all the other groups received ovalbumin(OVA) to establish murine asthma model. After successful modeling, the murines in high dose group and low dose group were orally administered with Fritillariae Cirrhosae Bulbus powder at the dose of 18.0 mgâ¢kg⻹ and 9.0 mgâ¢kg⻹, respectively; the murines in positive control group were injected intraperitoneally with dexamethasone at the dose of 0.5 mgâ¢kg⻹; while the murines in normal group and the model group were orally administered with the same volume of normal saline. All the drugs were given to murines per day for 28 d. The variations of airway responsiveness, variations of the total cell count and leukocyte differential count in bronchoalveolar lavage fluid(BALF), and the variations of thicknesses of bronchial wall and airway smooth muscle of each group were observed. The levels of MMP-2, MMP-9 and TIMP-1 were measured by ELISA; and the expression levels of MMP-2, MMP-9 and TIMP-1 mRNA were detected by RT-PCR. The results showed that as compared with the normal group, the airway responsiveness, the count of total cells, neutrophils, macrophage, lymphocytes, eosinophils in BALF, and the thicknesses of bronchial wall and airway smooth muscle were increased significantly in the model group(P<0.01); as compared with the model group, the above indicators were decreased significantly in the high dose group, low dose group and positive control group (P<0.05 or P<0.01). As compared with the normal group, the levels and expressions of MMP-2, MMP-9 and TIMP-1 mRNA were increased significantly in the model group(P<0.01); while as compared with the model group, these levels were decreased significantly in the high dose group, low dose group and positive control group(P<0.01). In conclusion, Fritillariae Cirrhosae Bulbus can improve airway remodeling in a murine asthma model, and its mechanisms may be related to down-regulating MMP-2, MMP-9 and TIMP-1 levels.
Assuntos
Asma/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Fritillaria/química , Raízes de Plantas/química , Animais , Modelos Animais de Doenças , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Aleatória , Inibidor Tecidual de Metaloproteinase-1/metabolismoRESUMO
As the leading cause of cancer-associated mortality globally among males in 2012, lung cancer is a disease of particular concern. Previously, the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) were revealed to be prognostic factors for various types of cancer, including lung cancer. In the present study, a retrospective review was conducted with patients who were diagnosed with lung cancer between January 1, 2000 and December 31, 2005 in the Fourth Hospital of Hebei Medical University. A total of 695 patients were included, and the optimal cutoffs of the NLR and the PLR were 6.0 and 248.0, respectively. There were statistically significant associations between tumor-node-metastasis (TNM) stage, surgery, metastasis incidence and NLR (P<0.001). The associations between TNM stage, surgery incidence and PLR were also revealed to be statistically significant (P<0.001). Patients in the low NLR group demonstrated longer overall survival (OS) than patients in the high NLR group (819.57 days vs. 629.86 days, P=0.041). The NLR at diagnosis was demonstrated to be an independent prognostic factor for OS. Thus, the NLR may be a promising approach for predicting the prognosis of patients with lung cancer.