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1.
Int J Med Sci ; 21(1): 61-69, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38164345

RESUMO

Background: Primary biliary cholangitis (PBC) is a rare autoimmune liver disease with few effective treatments and a poor prognosis, and its incidence is on the rise. There is an urgent need for more targeted treatment strategies to accurately identify high-risk patients. The use of stochastic survival forest models in machine learning is an innovative approach to constructing a prognostic model for PBC that can improve the prognosis by identifying high-risk patients for targeted treatment. Method: Based on the inclusion and exclusion criteria, the clinical data and follow-up data of patients diagnosed with PBC-associated cirrhosis between January 2011 and December 2021 at Taizhou Hospital of Zhejiang Province were retrospectively collected and analyzed. Data analyses and random survival forest model construction were based on the R language. Result: Through a Cox univariate regression analysis of 90 included samples and 46 variables, 17 variables with p-values <0.1 were selected for initial model construction. The out-of-bag (OOB) performance error was 0.2094, and K-fold cross-validation yielded an internal validation C-index of 0.8182. Through model selection, cholinesterase, bile acid, the white blood cell count, total bilirubin, and albumin were chosen for the final predictive model, with a final OOB performance error of 0.2002 and C-index of 0.7805. Using the final model, patients were stratified into high- and low-risk groups, which showed significant differences with a P value <0.0001. The area under the curve was used to evaluate the predictive ability for patients in the first, third, and fifth years, with respective results of 0.9595, 0.8898, and 0.9088. Conclusion: The present study constructed a prognostic model for PBC-associated cirrhosis patients using a random survival forest model, which accurately stratified patients into low- and high-risk groups. Treatment strategies can thus be more targeted, leading to improved outcomes for high-risk patients.


Assuntos
Cirrose Hepática Biliar , Humanos , Prognóstico , Cirrose Hepática Biliar/diagnóstico , Cirrose Hepática Biliar/tratamento farmacológico , Ácido Ursodesoxicólico/uso terapêutico , Estudos Retrospectivos , Cirrose Hepática/tratamento farmacológico
2.
J Transl Med ; 15(1): 221, 2017 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-29089030

RESUMO

BACKGROUND: There is increasing evidence that the existence of systemic inflammation response is correlated with poor prognosis in several solid tumors. The aim of this retrospective study was to investigate the association between systemic immune-inflammation index (SII) and therapy response and overall survival in patients with stage III non-small cell lung cancer (NSCLC). The prognostic values of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and prognostic nutritional index (PNI) were also evaluated. METHODS: In total, 332 patients with new diagnosis of stage III NSCLC were included in this retrospective analysis. SII was defined as platelet counts × neutrophil counts/lymphocyte counts. Receiver operating characteristic (ROC) curve was used to evaluate the optimal cut-off value for SII, NLR, PLR and PNI. Univariate and multivariate survival analysis were performed to identify the factors correlated with overall survival. RESULTS: Applying cut-offs of ≥ 660 (SII), ≥ 3.57 (NLR), ≥ 147 (PLR), ≤ 52.95 (PNI), SII ≥ 660 was significantly correlated with worse ECOG PS (< 0.001), higher T stage (< 0.001), advanced clinical stage (p = 0.019), and lower response rate (p = 0.018). In univariate analysis, SII ≥ 660, NLR ≥ 3.57, PLR ≥ 147, and PNI ≤ 52.95 were significantly associated with worse overall survival (p all < 0.001). Patients with SII ≥ 660 had a median overall survival of 10 months, and patients with SII < 660 showed a median overall survival of 30 months. In multivariate analysis only ECOG PS (HR, 1.744; 95% CI 1.158-2.626; p = 0.008), T stage (HR, 1.332; 95% CI 1.032-1.718; p = 0.028), N stage (HR, 1.848; 95% CI 1.113-3.068; p = 0.018), SII (HR, 2.105; 95% CI 1.481-2.741; p < 0.001) and NLR ≥ 3.57 (HR, 1.934; 95% CI 1.448-2.585; p < 0.001) were independently correlated with overall survival. CONCLUSIONS: This study demonstrates that the SII is an independent prognostic indicator of poor outcomes for patients with stage III NSCLC and is superior to other inflammation-based factors in terms of prognostic ability.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia , Inflamação/imunologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/terapia , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Inflamação/patologia , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Neutrófilos/patologia , Avaliação Nutricional , Contagem de Plaquetas , Curva ROC , Resultado do Tratamento
3.
Mol Carcinog ; 55(12): 2095-2105, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-26756568

RESUMO

To evaluate the clinical significance of lncRNAs in the resistance to cisplatin-based chemoradiotherapy in esophageal squamous cell carcinoma (ESCC). We focused on lncRNAs which were frequently reported in ESCC or were involved in chemoradiotherapy resistance. LncRNA expressions were examined in paired cisplatin-resistant and parental ESCC cell lines. Dysregulated lncRNAs were further measured in 162 pretreatment biopsy specimens of ESCC who received definitive chemoradiotherapy (dCRT). Then the correlations between lncRNA expression and response to dCRT and prognosis were analyzed. Three lncRNAs (AFAP1-AS1, UCA1, HOTAIR) were found to be deregulated in cisplatin-resistant cells compared with their parent cells. AFAP1-AS1 was significantly up-regulated in tumor tissues compared with adjacent normal tissues (P = 0.006). Furthermore, overexpression of AFAP1-AS1 was closely associated with lymph node metastasis (P < 0.001), distant metastasis (P = 0.016), advanced clinical stage (P = 0.002), and response to dCRT (P < 0.001). Kaplan-Meier survival analysis revealed that high expression of AFAP1-AS1 was significantly associated with shorter progression free survival (PFS) (median, 15 months vs. 27 months, P < 0.001) and overall survival (OS) (median, 29 months vs. 42 months, P < 0.001). In the multivariate analysis, high expression of AFAP1-AS1 was found to be an independent risk factor to predict poor PFS (HR, 1.626; P = 0.027) and OS (HR, 1.888; P = 0.004). Thus, high expression of AFAP1-AS1 could serve as a potential biomarker to predict tumor response and survival. Determination of this lncRNA expression might be useful for selection ESCC patients for dCRT. © 2016 The Authors. Molecular Carcinogenesis published by Wiley Periodicals, Inc.


Assuntos
Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Cisplatino/farmacologia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , Esôfago/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/genética , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/radioterapia , Linhagem Celular Tumoral , Quimiorradioterapia , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago , Esôfago/patologia , Esôfago/efeitos da radiação , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Regulação para Cima
4.
Sci Transl Med ; 16(743): eadk5395, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630847

RESUMO

Endoscopy is the primary modality for detecting asymptomatic esophageal squamous cell carcinoma (ESCC) and precancerous lesions. Improving detection rate remains challenging. We developed a system based on deep convolutional neural networks (CNNs) for detecting esophageal cancer and precancerous lesions [high-risk esophageal lesions (HrELs)] and validated its efficacy in improving HrEL detection rate in clinical practice (trial registration ChiCTR2100044126 at www.chictr.org.cn). Between April 2021 and March 2022, 3117 patients ≥50 years old were consecutively recruited from Taizhou Hospital, Zhejiang Province, and randomly assigned 1:1 to an experimental group (CNN-assisted endoscopy) or a control group (unassisted endoscopy) based on block randomization. The primary endpoint was the HrEL detection rate. In the intention-to-treat population, the HrEL detection rate [28 of 1556 (1.8%)] was significantly higher in the experimental group than in the control group [14 of 1561 (0.9%), P = 0.029], and the experimental group detection rate was twice that of the control group. Similar findings were observed between the experimental and control groups [28 of 1524 (1.9%) versus 13 of 1534 (0.9%), respectively; P = 0.021]. The system's sensitivity, specificity, and accuracy for detecting HrELs were 89.7, 98.5, and 98.2%, respectively. No adverse events occurred. The proposed system thus improved HrEL detection rate during endoscopy and was safe. Deep learning assistance may enhance early diagnosis and treatment of esophageal cancer and may become a useful tool for esophageal cancer screening.


Assuntos
Aprendizado Profundo , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Lesões Pré-Cancerosas , Humanos , Pessoa de Meia-Idade , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Estudos Prospectivos , Lesões Pré-Cancerosas/patologia
5.
World J Gastrointest Oncol ; 15(2): 225-239, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36908317

RESUMO

Colorectal cancer (CRC) is the second deadliest cancer and the third-most common malignancy in the world. Surgery, chemotherapy, and targeted therapy have been widely used to treat CRC, but some patients still develop resistance to these treatments. Ferroptosis is a novel non-apoptotic form of cell death. It is an iron-dependent non-apoptotic cell death characterized by the accumulation of lipid reactive oxygen species and has been suggested to play a role in reversing resistance to anticancer drugs. This review summarizes recent advances in the prognostic role of ferroptosis in CRC and the mechanism of action in CRC.

6.
Front Med (Lausanne) ; 9: 886853, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35652070

RESUMO

Convolutional neural networks in the field of artificial intelligence show great potential in image recognition. It assisted endoscopy to improve the detection rate of early gastric cancer. The 5-year survival rate for advanced gastric cancer is less than 30%, while the 5-year survival rate for early gastric cancer is more than 90%. Therefore, earlier screening for gastric cancer can lead to a better prognosis. However, the detection rate of early gastric cancer in China has been extremely low due to many factors, such as the presence of gastric cancer without obvious symptoms, difficulty identifying lesions by the naked eye, and a lack of experience among endoscopists. The introduction of artificial intelligence can help mitigate these shortcomings and greatly improve the accuracy of screening. According to relevant reports, the sensitivity and accuracy of artificial intelligence trained on deep cirrocumulus neural networks are better than those of endoscopists, and evaluations also take less time, which can greatly reduce the burden on endoscopists. In addition, artificial intelligence can also perform real-time detection and feedback on the inspection process of the endoscopist to standardize the operation of the endoscopist. AI has also shown great potential in training novice endoscopists. With the maturity of AI technology, AI has the ability to improve the detection rate of early gastric cancer in China and reduce the death rate of gastric cancer related diseases in China.

7.
World J Gastrointest Oncol ; 14(3): 690-702, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35321281

RESUMO

BACKGROUND: Gastric cancer (GC), a multifactorial disease, is caused by pathogens, such as Helicobacter pylori (H. pylori) and Epstein-Barr virus (EBV), and genetic components. AIM: To investigate microbiomes and host genome instability by cost-effective, low-coverage whole-genome sequencing, as biomarkers for GC subtyping. METHODS: Samples from 40 GC patients were collected from Taizhou Hospital, Zhejiang Province, affiliated with Wenzhou Medical University. DNA from the samples was subjected to low-coverage whole-genome sequencing with a median genome coverage of 1.86 × (range: 1.03 × to 3.17 ×) by Illumina × 10, followed by copy number analyses using a customized bioinformatics workflow ultrasensitive chromosomal aneuploidy detector. RESULTS: Of the 40 GC samples, 20 (50%) were found to be enriched with microbiomes. EBV DNA was detected in 5 GC patients (12.5%). H. pylori DNA was found in 15 (37.5%) patients. The other 20 (50%) patients were found to have relatively higher genomic instability. Copy number amplifications of the oncogenes, ERBB2 and KRAS, were found in 9 (22.5%) and 7 (17.5%) of the GC samples, respectively. EBV enrichment was found to be associated with tumors in the gastric cardia and fundus. H. pylori enrichment was found to be associated with tumors in the pylorus and antrum. Tumors with elevated genomic instability showed no localization and could be observed in any location. Additionally, H. pylori-enriched GC was found to be associated with the Borrmann type II/III and gastritis history. EBV-enriched GC was not associated with gastritis. No statistically significant correlation was observed between genomic instability and gastritis. Furthermore, these three different molecular subtypes showed distinct survival outcomes (P = 0.019). EBV-positive tumors had the best prognosis, whereas patients with high genomic instability (CIN+) showed the worst survival. Patients with H. pylori infection showed intermediate prognosis compared with the other two subtypes. CONCLUSION: Thus, using low-coverage whole-genome sequencing, GC can be classified into three categories based on disease etiology; this classification may prove useful for GC diagnosis and precision medicine.

8.
ACS Omega ; 6(29): 19342, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34337271

RESUMO

[This retracts the article DOI: 10.1021/acsomega.0c02072.].

9.
Int J Gen Med ; 14: 9913-9921, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34938110

RESUMO

PURPOSE: This study was designed to explore the optimal minimum segment width (MSW) in the intensity-modulated radiotherapy (IMRT) plan for esophageal cancer. PATIENTS AND METHODS: The imaging data of 20 esophageal cancer patients were selected for this study. Four IMRT plans were designed for each patient with MSWs of 0.5, 1.0, 1.5, and 2.0 cm. The conformity index (CI) and homogeneity index (HI) of the planning target volumes (PTV), organs at risk (OARs), control points (CP), monitor units (MU), plan delivery time (DT), and gamma passing rates (GPR) were collected and compared to appraise the treatment plan quality and delivery efficiency. RESULTS: Lower-MSW plans had larger CI and smaller HI values, and lower dose parameters of OARs and PTVs. The HI, CI, and dose parameter of OARs in the 0.5 and 1.0 cm MSW groups were similar and much better than those of the 1.5 and 2.0 cm MSW groups. Meanwhile, the plan in the 0.5 cm MSW group had significantly higher MUs, CPs, and DTs, and a significantly lower relative dose of GPR with a 3% dose difference and 3 mm distance to agreement criteria than the other three groups. CONCLUSION: The 0.5 and 1 cm MSW groups had better dosimetric parameters and IMRT plan quality than the other groups. However, plans with 0.5 cm MSW had worse delivery accuracy and efficiency than the other three groups. Thus, MSW of 1.0 cm was the optimal choice to ensure good quality, delivery accuracy, and treatment efficiency in IMRT plans for esophageal cancer.

10.
Int J Gen Med ; 14: 1057-1061, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33790634

RESUMO

AIM: This study aims to investigate the electrocardiogram characteristics of the different motor types of Parkinson's disease. METHODS: The data on 118 patients with Parkinson's disease (PD), who were initially diagnosed in the Outpatient and Inpatient Department, was collected. Among these 118 PD patients, 74 patients were assigned to the PIGD group, while 44 patients were assigned to the TD group, and their clinical features were analyzed, which included age, course, disease classification, and electrocardiogram parameters (PR, QRS, QT interval, and QTC). RESULTS: The QT interval in PD patients was positively correlated with the course of the disease and Hoehn-Yahr stage, and the QT interval in the PIGD group was longer than that in the TD group. CONCLUSION: A prolonged QT interval may indicate a longer disease period and a more severe disease condition.

11.
J Orthop Surg Res ; 16(1): 10, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407691

RESUMO

BACKGROUND: Osteoporosis (OP) is an age-related systemic bone disease. MicroRNAs (miRNAs) are involved in the regulation of osteogenic differentiation. The purpose of this study was to explore the role and mechanism of miR-1249-5p for promoting osteogenic differentiation of adipose-derived stem cells (ADSCs). METHODS: GSE74209 dataset was retrieved from NCBI Gene Expression Omnibus (GEO) database and performed bioinformatic analyses. OP tissue and healthy control tissues were obtained and used for RT-PCR analyses. ADSCs were incubated with miR-1249-5p mimic, inhibitor and corresponding negative control (NC), alkaline phosphatase (ALP) staining, and Alizarin Red Staining (ARS) were then performed to assess the role of miR-1249-5p for osteogenesis of ADSCs. Targetscan online website and dual-luciferase reporter assay were performed to verify that the 3'-UTR of PDX1 mRNA is a direct target of miR-1249-5p. RT-PCR and western blot were also performed to identify the mechanism of miR-1249-5p for osteogenesis of ADSCs. RESULTS: A total of 170 differentially expressed miRNAs were selected, among which, 75 miRNAs were downregulated and 95 miRNAs were upregulated. Moreover, miR-1249-5p was decreased in OP patients, while showed a gradual increase with the extension of induction time. miR-1249-5p mimic significantly increased osteogenic differentiation capacity and p-PI3K and p-Akt protein levels. Luciferase activity in ADSCs co-transfected of miR-1249-5p mimic with PDX1-WT reporter plasmids was remarkably decreased, but there was no obvious change in miR-1249-5p mimic with PDX1-MUT reporter plasmids co-transfection group. Overexpression PDX1 could partially reverse the promotion effects of miR-1249-5p on osteogenesis of ADSCs. CONCLUSION: In conclusion, miR-1249-5p promotes osteogenic differentiation of ADSCs by targeting PDX1 through the PI3K/Akt signaling pathway.


Assuntos
Adipócitos/fisiologia , Tecido Adiposo/citologia , Diferenciação Celular/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Expressão Gênica/genética , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , MicroRNAs/fisiologia , Osteogênese/genética , Células-Tronco/fisiologia , Transativadores/genética , Transativadores/metabolismo , Regiões 3' não Traduzidas , Células Cultivadas , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/fisiologia
12.
World J Gastroenterol ; 27(22): 3022-3036, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34168405

RESUMO

In the early December 2019, a novel coronavirus named severe acute respiratory syndrome coronavirus 2 was first reported in Wuhan, China, followed by an outbreak that spread around the world. Numerous studies have shown that liver injury is common in patients with coronavirus disease 2019 (COVID-19), and may aggravate the severity of the disease. However, the exact cause and specific mechanism of COVID-associated liver injury needs to be elucidated further. In this review, we present an analysis of the clinical features, potential mechanisms, and treatment strategies for liver injury associated with COVID-19. We hope that this review would benefit clinicians in devising better strategies for management of such patients.


Assuntos
COVID-19 , Hepatopatias/virologia , COVID-19/complicações , China/epidemiologia , Humanos , SARS-CoV-2
13.
Front Med (Lausanne) ; 8: 709347, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34368199

RESUMO

With the rapid development of science and technology, artificial intelligence (AI) systems are becoming ubiquitous, and their utility in gastroenteroscopy is beginning to be recognized. Digestive endoscopy is a conventional and reliable method of examining and diagnosing digestive tract diseases. However, with the increase in the number and types of endoscopy, problems such as a lack of skilled endoscopists and difference in the professional skill of doctors with different degrees of experience have become increasingly apparent. Most studies thus far have focused on using computers to detect and diagnose lesions, but improving the quality of endoscopic examination process itself is the basis for improving the detection rate and correctly diagnosing diseases. In the present study, we mainly reviewed the role of AI in monitoring systems, mainly through the endoscopic examination time, reducing the blind spot rate, improving the success rate for detecting high-risk lesions, evaluating intestinal preparation, increasing the detection rate of polyps, automatically collecting maps and writing reports. AI can even perform quality control evaluations for endoscopists, improve the detection rate of endoscopic lesions and reduce the burden on endoscopists.

14.
World J Gastroenterol ; 27(35): 5958-5966, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34629812

RESUMO

BACKGROUND: Endoscopic resection of duodenal subepithelial lesions (SELs) is a difficult procedure with a high risk of perforation. At present, dealing with perforation after endoscopic resection of duodenal SELs is still considered a great challenge. AIM: To evaluate the effectiveness and safety of an over-the-scope clip (OTSC) in the treatment of perforation post-endoscopic resection of duodenal SELs. METHODS: From May 2015 to November 2019, 18 patients with perforation following endoscopic resection of duodenal SELs were treated with OTSCs. Data comprising the rate of complete resection, closure of intraprocedural perforation, delayed bleeding, delayed perforation, and postoperative infection were extracted. RESULTS: The rate of complete removal of duodenal SELs and successful closure of the perforation was 100%. The median perforation size was 1 cm in diameter. Seventeen patients had minor intraoperative bleeding, while the remaining 1 patient had considerable amount of bleeding during the procedure. Seven patients had postoperative abdominal infections, of which 1 patient developed an abscess in the right iliac fossa and another patient developed septic shock. All 18 patients recovered and were discharged. No delayed bleeding or perforation was reported. The mean time taken to resume normal diet after the procedure was 6.5 d. The mean postoperative hospital stay was 9.5 d. No residual or recurrent lesions were detected during the follow-up period (15-66 mo). CONCLUSION: Closing a perforation after endoscopic resection of duodenal SELs with OTSCs seems to be an effective and reasonably safe therapeutic method.


Assuntos
Duodeno , Complicações Pós-Operatórias , Duodeno/cirurgia , Humanos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia
15.
Stem Cells Int ; 2021: 6930263, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34531915

RESUMO

Although liver transplantation is considered to be the best choice for patients with end-stage liver diseases, postoperative immune rejection still cannot be overlooked. Patients with liver transplantation have to take immunosuppressive drugs for a long time or even their entire lives, in which heavy economic burden and side effects caused by the drugs have become the major impediment for liver transplantation. There is a growing body of evidences indicating that mesenchymal stem cell (MSC) transplantation, a promising tool in regenerative medicine, can be used as an effective way to induce immune tolerance after liver transplantation based on their huge expansion potential and unique immunomodulatory properties. MSCs have been reported to inhibit innate immunity and adaptive immunity to induce a tolerogenic microenvironment. In in vitro studies, transplanted MSCs show plasticity in immune regulation by altering their viability, migration, differentiation, and secretion in the interactions with the surrounding host microenvironment. In this review, we aim to provide an overview of the current understanding of immunomodulatory properties of MSCs in liver transplantation, to elucidate the potential mechanisms behind MSCs regulating immune response, especially in vivo and the influence of the microenvironment, and ultimately to discuss the feasible strategies to improve the clinical prognosis of liver transplantation. Only after exhaustive understanding of potential mechanisms of the MSC immunomodulation can we improve the safety and effectiveness of MSC treatment and achieve better therapeutic effects.

16.
ACS Omega ; 5(36): 22840-22846, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32954132

RESUMO

The tumor microenvironment (TME) plays a significant role in weakening the effect of cancer immunotherapy, which calls for the remodeling of TME. Herein, we fabricated a nanostructured lipid carrier (NLC) to codeliver doxorubicin (Dox) and sorafenib (Sfn) as a drug delivery system (NLC/D-S). The Sfn was expected to regulate the TME of esophagus cancer. As a result, the immune response induced by Dox-related immunogenicity cell death could be fully realized. Our results demonstrated that Sfn was able to remodel the TME through downregulation of regulatory T cells (Treg), activation of effector T cells, and relieving of PD-1 expression, which achieved synergistic effect on the inhibition of primary tumor but also subsequent strong immune response on the regeneration of distant tumor.

17.
Kaohsiung J Med Sci ; 35(5): 277-283, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30897301

RESUMO

MicroRNA-26a (miR-26a) has been reported to be involved in the tumorigenesis of several tumors, but its biological function and molecular mechanism in multiple myeloma (MM) are still unknown. In this study, we found that overexpression of miR-26a obviously inhibited MM cell growth, and delayed tumor growth in xenografts. Further studies showed that overexpression of miR-26a induced cell cycle arrest at G0/G1 phase in MM cells. MiR-26a mimic down-regulated the expression levels of CDK6 and E2F1, but up-regulated p53 and p21 expression. In contrast, overexpression of CDK6 decreased the effect of miR-26a mimic on MM cell survival. Moreover, miR-26a targeted CDK6 mRNA and thus suppressed CDK6 protein expression. Overexpression of miR-26a also enhanced the cytotoxic action of doxorubicin against MM. These results demonstrated that miR-26a was involved in the development of MM through regulating CDK6 signaling pathway, and indicated that miR-26a could be as a novel target for anti-tumor therapy in clinic as a single strategy or in combination with other anti-tumor drugs in MM.


Assuntos
Carcinogênese/genética , Quinase 6 Dependente de Ciclina/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Mieloma Múltiplo/genética , RNA Mensageiro/genética , Animais , Antibióticos Antineoplásicos/farmacologia , Carcinogênese/metabolismo , Carcinogênese/patologia , Linhagem Celular Tumoral , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Doxorrubicina/farmacologia , Fator de Transcrição E2F1/antagonistas & inibidores , Fator de Transcrição E2F1/genética , Fator de Transcrição E2F1/metabolismo , Feminino , Humanos , Camundongos , Camundongos Nus , MicroRNAs/agonistas , MicroRNAs/metabolismo , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/metabolismo , Fase de Repouso do Ciclo Celular/genética , Transdução de Sinais , Carga Tumoral/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
18.
PLoS One ; 14(7): e0219213, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31265473

RESUMO

Recent studies have indicated an increased risk of dementia and Alzheimer's disease (AD) among people who consume proton pump inhibitors (PPIs), but the results of those studies are inconsistent. This meta-analysis aimed to explore the correction risk of dementia and AD among PPI users. The literature search for relevant studies was conducted in PubMed, Web of Science, EMBase and ScienceDirect. Pooled hazard ratio (HR) and 95% confidence intervals (CIs) were used to assess the relationship between the PPIs and risk of dementia and AD. Ten independent studies that involved 642305 participants were included in this meta-analysis. PPI users were unassociated with dementia (HR = 1.04, 95% CI 0.92-1.15; I2 = 95.6%, p < 0.001) and AD (HR = 0.96, 95% CI 0.83-1.09; I2 = 80.7%, p <0 .001). No evidence of publication bias was detected by Begg's and Egger's test. Sensitivity analyses showed no important differences in the estimates of effects. The current evidence indicates that PPI use does not increase dementia and AD risk. The remarkable heterogeneity among the studies warrants a further review of our findings.


Assuntos
Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/epidemiologia , Demência/induzido quimicamente , Demência/epidemiologia , Inibidores da Bomba de Prótons/efeitos adversos , Publicações , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Viés de Publicação , Análise de Regressão , Fatores de Risco
19.
Biomed Res Int ; 2019: 6360459, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428640

RESUMO

BACKGROUND: The predictive values of monocytes in the prognosis of patients with acute paraquat (PQ) poisoning are unclear. This retrospective study investigated the predictive values of monocytes in the prognosis of patients with acute PQ poisoning. METHODS: Adult patients who suffered from acute PQ poisoning in the emergency care unit of Cangzhou Central Hospital from May 2012 to December 2018 were enrolled. The patients were divided into groups, namely, survival and nonsurvival, according to a 90-day prognosis. Moreover, correlation, logistic regression, receiver-operator characteristic (ROC), and Kaplan-Meier curve analyses were applied to evaluate the monocyte values used to predict the prognosis of patients with acute PQ poisoning. RESULT: Among the 109 patients, 45 survived within 90 days after the poisoning, resulting in a 41.28% survival rate. The monocyte count of the nonsurvivors was significantly higher than that of the survivors (P< 0.001). Correlation analysis showed that monocyte count positively correlated with plasma PQ concentration (r= 0.413; P< 0.001) and negatively correlated with survival time (r= 0.512; P< 0.001) and 90-day survival (r= 0.503; P< 0.001). Logistic regression analysis showed that elevated monocytes were the independent risk factors for the 90-day survival. The area under the ROC curve of the monocyte count used to predict the 90-day survival was 0.826 (95% CI: 0.751-0.904), the optimal cut-off was 0.51×109/L, sensitivity was 73.4%, and specificity was 86.7%. CONCLUSION: This study demonstrated that elevated monocyte count is a useful early predictor of 90-day survival in patients with acute PQ poisoning. However, further studies are warranted to draw firm conclusions.


Assuntos
Monócitos , Paraquat/intoxicação , Doença Aguda , Adolescente , Adulto , Idoso , Criança , Intervalo Livre de Doença , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
20.
Medicine (Baltimore) ; 98(20): e15702, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096516

RESUMO

This study aimed to investigate the prognostic predictive value of the platelet-lymphocyte ratio (PLR) in patients with acute paraquat (PQ) intoxication.A total of 107 patients with acute PQ intoxication via oral ingestion were admitted in Cangzhou Central Hospital from May 2012 to September 2018. Valuable detection indices were screened out by using Cox proportional hazard regression and receiver operating characteristic (ROC) curve analyses, and their diagnostic efficiency was evaluated by using Kaplan-Meier curve.The 90-day mortality was 58.9% (63/107). The Kaplan-Meier curve showed that PLR was not associated with 90-day survival (log-rank test; P = .661). In Cox proportional hazard regression analyses, PLR was not an independent risk factor. Meanwhile, the ROC curves showed that PLR had an AUC value of 0.569 (95% confidence interval: 0.459-0.679, P = .227) in predicting 90-day survival.PLR is not a prognostic predictor for patients with acute PQ intoxication.


Assuntos
Plaquetas/citologia , Linfócitos/citologia , Intoxicação por Organofosfatos/sangue , Paraquat/intoxicação , Adulto , China/epidemiologia , Serviço Hospitalar de Emergência , Feminino , Lavagem Gástrica/métodos , Herbicidas/efeitos adversos , Herbicidas/intoxicação , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Intoxicação por Organofosfatos/complicações , Intoxicação por Organofosfatos/diagnóstico , Intoxicação por Organofosfatos/mortalidade , Paraquat/efeitos adversos , Contagem de Plaquetas/métodos , Estudos Retrospectivos , Tempo para o Tratamento/estatística & dados numéricos , Tempo para o Tratamento/tendências
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