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1.
Sci Rep ; 14(1): 6943, 2024 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-38521854

RESUMO

Limited population-based studies discuss the association between fat mass index (FMI) and the risk of liver diseases. This investigation utilized data from the National Health and Nutrition Examination Survey (NHANES) to examine the linkage between the FMI and liver conditions, specifically steatosis and fibrosis. The study leveraged data from NHANES's 2017-2018 cross-sectional study, employing an oversampling technique to deal with sample imbalance. Hepatic steatosis and fibrosis were identified by vibration-controlled transient elastography. Receiver operating curve was used to assess the relationship of anthropometric indicators, e.g., the FMI, body mass index (BMI), weight-adjusted-waist index (WWI), percentage of body fat (BF%), waist-to-hip ratio (WHR), and appendicular skeletal muscle index (ASMI), with hepatic steatosis and fibrosis. In this study, which included 2260 participants, multivariate logistic regression models, stratified analyses, restricted cubic spline (RCS), and sharp regression discontinuity analyses were utilized. The results indicated that the WHR and the FMI achieved the highest area under the curve for identifying hepatic steatosis and fibrosis, respectively (0.720 and 0.726). Notably, the FMI presented the highest adjusted odds ratio for both hepatic steatosis (6.40 [4.91-8.38], p = 2.34e-42) and fibrosis (6.06 [5.00, 7.37], p = 5.88e-74). Additionally, potential interaction effects were observed between the FMI and variables such as the family income-to-poverty ratio, smoking status, and hypertension, all of which correlated with the presence of liver fibrosis (p for interaction < 0.05). The RCS models further confirmed a significant positive correlation of the FMI with the controlled attenuation parameter and liver stiffness measurements. Overall, the findings underscore the strong link between the FMI and liver conditions, proposing the FMI as a potential straightforward marker for identifying liver diseases.


Assuntos
Fígado Gorduroso , Hepatopatia Gordurosa não Alcoólica , Humanos , Inquéritos Nutricionais , Estudos Transversais , Índice de Massa Corporal , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/epidemiologia
2.
Clin Transl Med ; 13(11): e1479, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37983927

RESUMO

BACKGROUND: Alternative splicing (AS) is an omnipresent regulatory mechanism of gene expression that enables the generation of diverse splice isoforms from a single gene. Recently, AS events have gained considerable momentum in the pathogenesis of inflammatory bowel disease (IBD). METHODS: Our review has summarized the complex process of RNA splicing, and firstly highlighted the potential involved molecules that target aberrant splicing events in IBD. The quantitative transcriptome analyses such as microarrays, next-generation sequencing (NGS) for AS events in IBD have been also discussed. RESULTS: Available evidence suggests that some abnormal splicing RNAs can lead to multiple intestinal disorders during the onset of IBD as well as the progression to colitis-associated cancer (CAC), including gut microbiota perturbations, intestinal barrier dysfunctions, innate/adaptive immune dysregulations, pro-fibrosis activation and some other risk factors. Moreover, current data show that the advanced technologies, including microarrays and NGS, have been pioneeringly employed to screen the AS candidates and elucidate the potential regulatory mechanisms of IBD. Besides, other biotechnological progresses such as the applications of third-generation sequencing (TGS), single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST), will be desired with great expectations. CONCLUSIONS: To our knowledge, the current review is the first one to evaluate the potential regulatory mechanisms of AS events in IBD. The expanding list of aberrantly spliced genes in IBD along with the developed technologies provide us new clues to how IBD develops, and how these important AS events can be explored for future treatment.


Assuntos
Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Humanos , Processamento Alternativo/genética , Doenças Inflamatórias Intestinais/genética , Splicing de RNA , Fatores de Risco
3.
J Spinal Cord Med ; : 1-9, 2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37428443

RESUMO

OBJECTIVE: To validate the Chinese version of the Community Integration Questionnaire-Revised (CIQ-R-C) for individuals with spinal cord injury. DESIGN: Cross-sectional study. SETTING: Shanghai Sunshine Rehabilitation Center. PARTICIPANTS: 317 adults with spinal cord injury in a rehabilitation center in Mainland China. INTERVENTIONS: Not applicable. METHODS: The CIQ-R-C (including an additional e-shopping item), global QoL, Zung Self-Rating Anxiety/Depression Scale (SAS/SDS), and Multidimensional Scale of Perceived Social Support (MSPSS) were administered. Reliability and validity analyses were conducted. RESULTS: Good item-domain correlations were found for 15 of the 16-item original CIQ-R, except for item 10 (leisure alone or with others). Exploratory Factor Analysis supported a construct of the CIQ-R-C (excluding item 10) as made of four domains (CFI = 0.94; RMSEA = 0.06): home, social engagement, digital social networking, and traditional social networking. Good internal consistency and test-retest reliability were observed in the total and the home subscale of the CIQ-R-C. Satisfactory construct validity was shown by the correlation analysis among the CIQ-R-C Scale, SAS/SDS, global QoL, and MSPSS. CONCLUSION: The CIQ-R-C Scale is valid and reliable, and can be used to assess community integration of individuals with spinal cord injury in China.

4.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 35(4): 421-426, 2023 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-37308200

RESUMO

OBJECTIVE: To establish a machine learning model based on extreme gradient boosting (XGBoost) algorithm for early prediction of severe acute pancreatitis (SAP), and explore its predictive efficiency. METHODS: A retrospective cohort study was conducted. The patients with acute pancreatitis (AP) who admitted to the First Affiliated Hospital of Soochow University, the Second Affiliated Hospital of Soochow University and Changshu Hospital Affiliated to Soochow University from January 1, 2020 to December 31, 2021 were enrolled. Demography information, etiology, past history, and clinical indicators and imaging data within 48 hours of admission were collected according to the medical record system and image system, and the modified CT severity index (MCTSI), Ranson score, bedside index for severity in acute pancreatitis (BISAP) and acute pancreatitis risk score (SABP) were calculated. The data sets of the First Affiliated Hospital of Soochow University and Changshu Hospital Affiliated to Soochow University were randomly divided into training set and validation set according to 8 : 2. Based on XGBoost algorithm, the SAP prediction model was constructed on the basis of hyperparameter adjustment by 5-fold cross validation and loss function. The data set of the Second Affiliated Hospital of Soochow University was served as independent test set. The predictive efficacy of the XGBoost model was evaluated by drawing the receiver operator characteristic curve (ROC curve), and compared it with the traditional AP related severity score; variable importance ranking diagram and Shapley additive explanation (SHAP) diagram were drawn to visually explain the model. RESULTS: A total of 1 183 AP patients were enrolled finally, of which 129 (10.9%) developed SAP. Among the patients from the First Affiliated Hospital of Soochow University and Changshu Hospital Affiliated to Soochow University, there were 786 patients in the training set and 197 in the validation set; 200 patients from the Second Affiliated Hospital of Soochow University were used as the test set. Analysis of all three datasets showed that patients who advanced to SAP exhibited pathological manifestation such as abnormal respiratory function, coagulation function, liver and kidney function, and lipid metabolism. Based on the XGBoost algorithm, an SAP prediction model was constructed, and ROC curve analysis showed that the accuracy for prediction of SAP reached 0.830, the area under the ROC curve (AUC) was 0.927, which was significantly improved compared with the traditional scoring systems including MCTSI, Ranson, BISAP and SABP, the accuracy was 0.610, 0.690, 0.763, 0.625, and the AUC was 0.689, 0.631, 0.875, and 0.770, respectively. The feature importance analysis based on the XGBoost model showed that the top ten items ranked by the importance of model features were admission pleural effusion (0.119), albumin (Alb, 0.049), triglycerides (TG, 0.036), Ca2+ (0.034), prothrombin time (PT, 0.031), systemic inflammatory response syndrome (SIRS, 0.031), C-reactive protein (CRP, 0.031), platelet count (PLT, 0.030), lactate dehydrogenase (LDH, 0.029), and alkaline phosphatase (ALP, 0.028). The above indicators were of great significance for the XGBoost model to predict SAP. The SHAP contribution analysis based on the XGBoost model showed that the risk of SAP increased significantly when patients had pleural effusion and decreased Alb. CONCLUSIONS: A SAP prediction scoring system was established based on the machine automatic learning XGBoost algorithm, which can predict the SAP risk of patients within 48 hours of admission with good accuracy.


Assuntos
Pancreatite , Humanos , Doença Aguda , Estudos Retrospectivos , Hospitalização , Algoritmos
5.
Clin Transl Med ; 13(5): e1253, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37138536

RESUMO

BACKGROUND: Colitis-associated cancer (CAC) is one of the most severe complications of inflammatory bowel disease (IBD), which has caused a worse survival rate in IBD patients. Although the exact aetiology and pathogenesis of CAC are not completely elucidated, evidence indicates that non-coding RNAs are closely involved and play a key role. METHODS: This review aims to summarise the major findings of non-coding RNAs in the development of CAC and present the potential mechanistic links between non-coding RNAs and CAC pathogenesis. The results show that non-coding RNAs can hinder DNA mismatch repair proteins and obstruct chromosome passenger complexes to increase microsatellite instability and accumulate chromosomal instability, respectively. The data also suggest that DNA promoter methylation or RNA methylation modifications of non-coding RNA are the main mechanisms to regulate oncogene or tumour suppressor expression during the CAC progression. Other factors, including gut microbiota perturbations, immune dysregulation and barrier dysfunction, are also regulated and influenced by non-coding RNAs. Besides, non-coding RNAs as molecular managers are associated with multiple critical signalling pathways governing the initiation, progression and metastasis of CAC, including the janus kinase/signal transducer and activator of transcription (JAK/STAT), nuclear factor-kappa B (NF-κB), extracellular signal-regulated kinase (ERK), Toll-like receptor 4 (TLR4), Wnt/ß-catenin and phosphatidylinositol 3-Kinase/Protein Kinase B (PI3K/AKT) pathways. In addition, non-coding RNAs can be detected in colon tissues or blood, and their aberrant expressions and diagnostic and prognostic roles are also discussed and confirmed in CAC patients. CONCLUSIONS: It is believed that a deepening understanding of non-coding RNAs in CAC pathogenesis may prevent the progression to carcinogenesis, and will offer new effective therapies for CAC patients.


Assuntos
Neoplasias Associadas a Colite , Doenças Inflamatórias Intestinais , Neoplasias , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/genética , Transdução de Sinais/genética
6.
Heliyon ; 9(3): e13841, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36873552

RESUMO

Objectives: There is limited information about coronary heart disease (CHD) in adults with physical disabilities. This study was performed to assess the incidence and predictors of the new development of CHD in adults with physical disabilities. Methods: A retrospective cohort study was performed on 3902 physically disabled people in Shanghai, China. Baseline information was collected in January 2012, and participants were followed-up with for 7.5 years for CHD events. Risk factors for demographic characteristics, disease history, electrocardiography, and blood biochemical indicators were evaluated using a Cox proportional hazard model. Subgroup analyzes were performed according to gender and level of physical disability. Results: Out of the total 3902 adults with physical disabilities (average age 55.9 ± 8.5 years), 468 (12.0%) developed CHD, during a median follow-up period of 7 years. Independent predictors of CHD included the following: age (HR = 1.411, 95% CI = 1.255-1.587, p<0.001), gender (HR = 0.773, 95% CI = 0.637-0.940, p = 0.010), abnormal electrocardiogram(HR = 1.396, 95% CI = 1.088-1.792, p = 0.009), hypertension (HR = 1.657, 95% CI = 1.369-2.006, p<0.001), diabetes (HR = 1.649, 95% CI = 1.307-2.081, p<0.001), serum uric acid (HR = 1.001, 95% CI = 1.000-1.002, p = 0.046), and total cholesterol (HR = 1.416, 95% CI = 1.054-1.902, p = 0.021). In addition to the risk factors of the total population with physical disability, triglyceride was also a significant risk factor for CHD in the subgroup with women and mild disability. Conclusions: During a 7.5 years period, the CHD incidence rate among physically disabled people was 12.0%. We identified the role of CHD risk factors such as age, gender, hypertension, diabetes, serum uric acid, total cholesterol, and abnormal electrocardiogram.

7.
Oncol Lett ; 25(4): 151, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36936023

RESUMO

Exposed endoscopic full-thickness resection (Eo-EFTR) has been recognized as a feasible therapy for gastrointestinal submucosal tumours (SMTs) originating deep in the muscularis propria layer; however, Eo-EFTR is difficult to perform in a retroflexed fashion in the gastric fundus. As a supportive technique, clip- and snare-assisted traction may help expose the surgical field and shorten the operation time in endoscopic resection of difficult regions. However, the application of clip- and snare-assisted traction in Eo-EFTR of SMTs in the gastric fundus is limited. Between April 2018 and December 2021, Eo-EFTR with clip- and snare-assisted traction was performed in 20 patients with SMTs in the gastric fundus at The First Affiliated Hospital of Soochow University. The relevant clinical data were collected retrospectively for all of the patients and analysed. All 20 patients underwent Eo-EFTR successfully without conversion to open surgery or severe adverse events. The en bloc resection rate and R0 resection rate were both 100%. Two patients had abdominal pain and fever after the operation, and five patients had fever, which recovered with medical therapy. No complications, such as delayed bleeding or delayed perforation, were observed. The postoperative pathology indicated that 19 cases were gastrointestinal stromal tumours and one case was leiomyoma. During the follow-up, no residual tumour, local recurrence or distant metastasis was detected by endoscopy or abdominal computed tomography. In conclusion, Eo-EFTR with clip- and snare-assisted traction appears to be a relatively safe and effective treatment for gastric SMTs in the fundus. However, prospective studies on a larger sample size are required to verify the effect of the clip- and snare-assisted traction in Eo-EFTR.

8.
J Clin Transl Hepatol ; 11(2): 452-458, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-36643028

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. The mechanisms involved in NAFLD onset are complicated and multifactorial. Recent literature has indicated that altered intestinal barrier function is related to the occurrence and progression of liver disease. The intestinal barrier is important for absorbing nutrients and electrolytes and for defending against toxins and antigens in the enteric environment. Major mechanisms by which the intestinal barrier influences the development of NAFLD involve the altered epithelial layer, decreased intracellular junction integrity, and increased intestinal barrier permeability. Increased intestinal permeability leads to luminal dysbiosis and allows the translocation of pathogenic bacteria and metabolites into the liver, inducing inflammation, immune response, and hepatocyte injury in NAFLD. Although research has been directed to NAFLD in recent decades, the pathophysiological changes in NAFLD initiation and progression are still not completely understood, and the therapeutic targets remain limited. A deeper understanding on the correlation between NAFLD pathogenesis and intestinal barrier regulation must be attained. Therefore, in this review, the components of the intestinal barrier and their respective functions and disruptions during the progression of NAFLD are discussed.

9.
J Pers Med ; 12(11)2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36422105

RESUMO

OBJECTIVE: To evaluate the feasibility of automated machine learning (AutoML) in predicting 30-day mortality in non-cholestatic cirrhosis. METHODS: A total of 932 cirrhotic patients were included from the First Affiliated Hospital of Soochow University between 2014 and 2020. Participants were divided into training and validation datasets at a ratio of 8.5:1.5. Models were developed on the H2O AutoML platform in the training dataset, and then were evaluated in the validation dataset by area under receiver operating characteristic curves (AUC). The best AutoML model was interpreted by SHapley Additive exPlanation (SHAP) Plot, Partial Dependence Plots (PDP), and Local Interpretable Model Agnostic Explanation (LIME). RESULTS: The model, based on the extreme gradient boosting (XGBoost) algorithm, performed better (AUC 0.888) than the other AutoML models (logistic regression 0.673, gradient boost machine 0.886, random forest 0.866, deep learning 0.830, stacking 0.850), as well as the existing scorings (the model of end-stage liver disease [MELD] score 0.778, MELD-Na score 0.782, and albumin-bilirubin [ALBI] score 0.662). The most key variable in the XGBoost model was high-density lipoprotein cholesterol, followed by creatinine, white blood cell count, international normalized ratio, etc. Conclusion: The AutoML model based on the XGBoost algorithm presented better performance than the existing scoring systems for predicting 30-day mortality in patients with non-cholestatic cirrhosis. It shows the promise of AutoML in its future medical application.

10.
J Transl Med ; 20(1): 58, 2022 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-35101080

RESUMO

BACKGROUND: Colon cancer is a common malignant tumor of the digestive tract, and its incidence is ranked third among gastrointestinal tumors. The present study aims to investigate the role of a novel circular RNA (circCSPP1) in colon cancer and its underlying molecular mechanisms. METHODS: Bioinformatics analysis and reverse transcription-quantitative PCR were used to detect the expression levels of circCSPP1 in colon cancer tissues and cell lines. The effects of circCSPP1 on the behavior of colon cancer cells were investigated using CCK-8, transwell and clonogenic assays. Bioinformatics analysis along with luciferase, fluorescence in situ hybridization and RNA pull-down assays were used to reveal the interaction between circCSPP1, microRNA (miR)-431, Rho associated coiled-coil containing protein kinase 1 (ROCK1) and zinc finger E-box binding homeobox 1 (ZEB1). RESULTS: It was found that circCSPP1 expression was significantly upregulated in colon cancer tissues and cell lines. Overexpression of circCSPP1 significantly promoted the proliferation, migration and invasion of colon cancer cells, whereas silencing of circCSPP1 exerted opposite effects. Mechanistically, circCSPP1 was found to bind with miR-431. In addition, ROCK1 and ZEB1 were identified as the target genes of miR-431. Rescue experiments further confirmed the interaction between circCSPP1, miR-431, ROCK1 and ZEB1. Moreover, circCSPP1 promoted the expression level of ROCK1, cyclin D1, cyclin-dependent kinase 4, ZEB1 and Snail, and lowered the E-cadherin expression level. CONCLUSION: Taken together, the findings of the present study indicated that circCSPP1 may function as a competing endogenous RNA in the progression of colon cancer by regulating the miR-431/ROCK1 and miR-431/ZEB1 signaling axes.


Assuntos
Neoplasias do Colo , MicroRNAs , RNA Circular , Homeobox 1 de Ligação a E-box em Dedo de Zinco , Quinases Associadas a rho , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Hibridização in Situ Fluorescente , MicroRNAs/genética , RNA Circular/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , Quinases Associadas a rho/genética , Quinases Associadas a rho/metabolismo
11.
Clin Transl Med ; 12(2): e683, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35184406

RESUMO

BACKGROUND: Emerging studies have proved that colonic inflammation caused by refractory inflammatory bowel disease (IBD) can initiate the colitis-associated cancer (CAC), but the transition from inflammation to carcinoma is still largely unknown. METHODS: In this study, mouse colitis and CAC models were established, and the RNA-seq by circRNA microarray was employed to identify the differentially expressed circRNAs and mRNAs in different comparisons (DSS vs. NC and AOM/DSS vs. DSS). The bioinformatics analyses were used to search the common characteristics in mouse colitis and CAC. RESULTS: The K-means clustering algorithm packaged these differential expressed circRNAs into subgroup analysis, and the data strongly implied that mmu_circ_0001109 closely correlated to the pro-inflammatory signals, while mmu_circ_0001845 was significantly associated with the Wnt signalling pathway. Our subsequent data in vivo and in vitro confirmed that mmu_circ_0001109 could exacerbate the colitis by up-regulating the Jak-STAT3 and NF-kappa B signalling pathways, and mmu_circ_0001845 promoted the CAC transformation through the Wnt signalling pathway. By RNA blasting between mice and humans, the human RTEL1- and PRKAR2A-derived circRNAs, which might be considered as homeotic circRNAs of mmu_circ_0001109 and mmu_circ_0001845, respectively, were identified. The clinical data revealed that RTEL1-derived circRNAs had no clinical significance in human IBD and CAC. However, three PRKAR2A-derived circRNAs, which had the high RNA similarities to mmu_circ_0001845, were remarkably up-regulated in CAC tissue samples and promoted the transition from colitis to CAC. CONCLUSIONS: Our results suggested that these human PRKAR2A-derived circRNAs could be novel candidates for distinguishing CAC patients and predicted the prognosis of CAC.


Assuntos
Colite/complicações , Neoplasias Colorretais/classificação , Subunidade RIIalfa da Proteína Quinase Dependente de AMP Cíclico/efeitos adversos , Neoplasias/classificação , Animais , Colite/genética , Neoplasias Colorretais/etiologia , Subunidade RIIalfa da Proteína Quinase Dependente de AMP Cíclico/genética , Subunidade RIIalfa da Proteína Quinase Dependente de AMP Cíclico/metabolismo , Modelos Animais de Doenças , Camundongos , Neoplasias/etiologia , RNA Circular
12.
Redox Biol ; 46: 102076, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34315112

RESUMO

Acquired resistance to tyrosine kinase inhibitors (TKIs) is the major obstacle to improve clinical efficacy in cancer patients. The epithelial-stromal interaction in tumor microenvironment influences cancer drug response to TKIs. Anlotinib is a novel oral multi-targeted TKI, and has recently been proven to be effective and safe for several tumors. However, if and how the epithelial-stromal interaction in tumor microenvironment affects anlotinib response in gastric cancer (GC) is not known. In this study, we found that anlotinib inhibited GC cells growth by inducing GC cells apoptosis and G2/M phase arrest in a dose- and time-dependent manner. Reactive oxygen species (ROS) mediated anlotinib-induced apoptosis in GC cells, while cancer-associated fibroblasts (CAFs) significantly suppressed anlotinib-induced apoptosis and ROS in GC cells. Increased BDNF that was derived from CAFs activated TrkB-Nrf2 signaling in GC cells, and reduced GC cells response to anlotinib. We identified secreted lactate from GC cells as the key molecule instructing CAFs to produce BDNF in a NF-κB-dependent manner. Additionally, functional targeting BDNF-TrkB pathway with neutralizing antibodies against BDNF and TrkB increased the sensitivity of GC cells towards anlotinib in human patient-derived organoid (PDO) model. Taken together, these results characterize a critical role of the epithelial-stroma interaction mediated by the lactate/BDNF/TrkB signaling in GC anlotinib resistance, and provide a novel option to overcome drug resistance.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Neoplasias Gástricas , Fator Neurotrófico Derivado do Encéfalo/genética , Fibroblastos , Humanos , Indóis , Ácido Láctico , Quinolinas , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Microambiente Tumoral
13.
Mol Ther Nucleic Acids ; 23: 1288-1303, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33717650

RESUMO

Tumor metastasis is a crucial impediment to the treatment of gastric cancer (GC), and the epithelial-to-mesenchymal transition (EMT) program plays a critical role for the initiation of GC metastasis. Thus, the aim of this study is to investigate the regulation of lnc-CTSLP4 in the EMT process during GC progression. We found that lnc-CTSLP4 was significantly downregulated in GC tumor tissues compared with adjacent non-tumor tissues, and its levels in GC tumor tissues were closely correlated with tumor local invasion, TNM stage, lymph node metastasis, and prognosis of GC patients. Loss- and gain-of-function assays indicated that lnc-CTSLP4 inhibited GC cell migration, invasion, and EMT in vitro, as well as peritoneal dissemination in vivo. Mechanistic analysis demonstrated that lnc-CTSLP4 could bind with Hsp90α/heterogeneous nuclear ribonucleoprotein AB (HNRNPAB) complex and recruit E3-ubiquitin ligase ZFP91 to induce the degradation of HNRNPAB, thus suppressing the transcriptional activation of Snail and ultimately reversing EMT of GC cells. Taken together, our results suggest that lnc-CTSLP4 is significantly downregulated in GC tumor tissues and inhibits metastatic potential of GC cells by attenuating HNRNPAB-dependent Snail transcription via interacting with Hsp90α and recruiting E3 ubiquitin ligase ZFP91, which shows that lnc-CTSLP4 could serve as a prognostic biomarker and therapeutic target for metastatic GC.

14.
Esophagus ; 18(1): 144-151, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32519226

RESUMO

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder. Proton pump inhibitors (PPIs) are first-line drugs for GERD. For those who fail to respond to PPIs, adding prokinetics to PPIs is recommended and several trials have been conducted to evaluate the efficacy of prokinetic-PPI combination therapy. METHODS: A systematic literature search was performed using PubMed and the Cochrane Library databases before February 2019 for randomized controlled trials (RCTs), which compared the efficacy of prokinetics plus PPI treatment with that of PPI monotherapy. Relevant studies were examined and data were extracted independently by two investigators. The risk ratios (RRs) with 95% CIs were used to evaluate the responder rate, and standard mean differences (SMDs) or mean differences (MDs) with 95% CIs were used for symptom score changes. Statistical heterogeneity was evaluated by the I2 statistic. Either a fixed-effect or a random-effect model was established for calculating the pooled data. RESULTS: A total of 14 studies, comprising 1,437 patients were ultimately included in the meta-analysis. The pooled analysis showed that compared to PPI monotherapy, addition of prokinetics to PPI did not elevate the rate of endoscopic responders (RR = 0.996, 95% CI 0.929 - 1.068, p = 0.917), but improved symptom response (RR = 1.185, 95% CI 1.042 - 1.348, p = 0.010). Additionally, the combined therapy achieved a greater symptom relief than monotherapy both in FSSG and GERD-Q subgroups (MD = - 2.978, 95% CI - 3.319 to - 2.638, p < 0.001; MD = - 0.723, 95% CI - 0.968 to - 0.478, p < 0.001). CONCLUSIONS: Adding prokinetics to PPIs achieves symptomatic improvement compared to PPI monotherapy, thus can enhance life quality of GERD patients. However, the combined treatment seems to have no significant effect on mucosal healing.


Assuntos
Refluxo Gastroesofágico , Inibidores da Bomba de Prótons , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Humanos , Inibidores da Bomba de Prótons/uso terapêutico , Resultado do Tratamento
16.
BMC Health Serv Res ; 20(1): 298, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32293434

RESUMO

BACKGROUND: Specialized Institution-Based Rehabilitation (SIBR) is the cornerstone of care and treatment for individuals with spinal cord injury, but most people with chronic spinal cord injury (CSCI) living in China have no SIBR experience after acute care hospital discharge. In 2009, an SIBR facility was set up in Shanghai (China) to fill this important gap in care. The purpose of the study was to evaluate the effectiveness of an integrated rehabilitation training program among individuals with CSCI living in Shanghai. METHODS: A within-subject pre-posttest design was used to evaluate the SIBR. The sample included 455 individuals ≥1 year post-SCI, who were older than 18 years of age and were enrolled in a rehabilitation center in Shanghai, China, between 2013 and 2019. The data included individuals' sociodemographic and injury characteristics, and twenty-three indicators were used as outcome measurements to evaluate basic life skills and their applications in family and social life. Multivariate linear regression was conducted to determine which factors might have influenced the effectiveness of the SIBR. RESULTS: All basic life skills and their applications in family and social life were improved, but with variations across socio-demographics. Female individuals with CSCI had better outcomes in basic life skills than did males. In terms of basic life skills and their applications in family and social life, individuals with a low level (thoracic or lumbosacral) of injury achieved more significant functional gains than those with a higher level (cervical). The baseline score was also a relevant factor in functional outcome. CONCLUSIONS: Even for individuals with a long SCI history, SIBR training can improve basic life skills and the applications of those skills in family and social life settings.


Assuntos
Traumatismos da Medula Espinal/reabilitação , Adulto , China , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Programas e Projetos de Saúde , Centros de Reabilitação
17.
Spinal Cord ; 58(2): 216-223, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31477810

RESUMO

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To evaluate the effects of two periods of rehabilitation among people with spinal cord injury (SCI). SETTING: Shanghai Sunshine Rehabilitation Center (SSRC), China. METHODS: A total of 130 people with SCI who received two periods of rehabilitation participated in the study. Outcome measures included basic life skills (15 items) and their applications in family and social life (8 items). Six factors were identified from the 23 items by factor analysis: self-care and transfer skills; basic life skills application in social life; cognition and emotion; basic life skills application in family life; walking and climbing stairs; and wheelchair skills. Standardized scores ranging from 0 to 100 were used to show the rehabilitation outcome in a histogram. RESULTS: Median scores for self-care and transfer skills, wheelchair skills, cognition and emotion, and their applications in family and social life improved significantly (7-80%, p < 0.01) over the first rehabilitation period, while no improvement was observed in walking and climbing stairs. Five factors showed a significant sustained effect (p < 0.01) upon admission to the second rehabilitation period, except walking and climbing stairs. By enrolling in the second period of rehabilitation, participants acquired significant additional improvement (5-43%, p < 0.01) in rehabilitation outcomes, except in cognition and emotion, walking and climbing stairs. CONCLUSIONS: Two periods of rehabilitation were efficacious at increasing the abilities of basic life skills and their applications in family and social life. The potential benefits of continuous rehabilitation merit further research.


Assuntos
Reabilitação Neurológica , Terapia Ocupacional , Avaliação de Resultados em Cuidados de Saúde , Educação de Pacientes como Assunto , Traumatismos da Medula Espinal/reabilitação , Atividades Cotidianas , Adolescente , Adulto , Idoso , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reabilitação Neurológica/métodos , Terapia Ocupacional/métodos , Estudos Retrospectivos , Adulto Jovem
18.
World J Surg Oncol ; 17(1): 75, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31039803

RESUMO

BACKGROUND: The Toronto hepatocellular carcinoma (HCC) risk index (THRI) was developed to predict HCC in patients with cirrhosis. This study aimed to validate the THRI in a 10-year Asian cohort. METHODS: A total of 2836 patients with cirrhosis at the First Affiliated Hospital of Soochow University between January 2008 and May 2018 were evaluated. Based on the THRI value at diagnosis, patients were divided into three groups (< 120, low-risk; 120-240, intermediate-risk; > 240, high-risk). Student's t test and Fisher's exact test were applied to compare parameters between the HCC group and the non-HCC group. The receiver operator characteristic (ROC) curve was drafted to identify the value of the THRI in predicting HCC. Logistic regression was utilized to assess the relationship between the development of HCC and THRI values. The incidence of HCC was calculated for the three groups using the Kaplan-Meier method, and curves were compared using the log-rank test. RESULTS: Of 520 patients enrolled in this study, 76 patients developed HCC. Patients who developed HCC had a higher THRI score than those who did not develop HCC (279.5 ± 57.1 vs. 232.3 ± 67.6, respectively, p < 0.001). The area under the ROC curve for the THRI to predict HCC was 0.707 ([95% CI 0.645-0.769], p < 0.001), with a sensitivity of 0.842 and a specificity of 0.486 when the cutoff THRI value was 226. Compared to the low-risk group, the high-risk group presented higher odds of developing HCC (adjusting odds ratio 1.026 [95% CI 1.002-1.051], p = 0.036). Differences existed in the cumulative incidence of HCC among the three risk groups (log-rank, p < 0.001). The 5-year cumulative HCC incidence of the low-risk group, intermediate-risk group, and high-risk group was 0%, 13%, and 34%, respectively. CONCLUSION: This study validated THRI values for predicting HCC in Asians with cirrhosis, which presented a fine sensitivity to identify the high-risk population of HCC for secondary prevention.


Assuntos
Carcinoma Hepatocelular/etiologia , Cirrose Hepática/complicações , Neoplasias Hepáticas/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/patologia , China/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Testes de Função Hepática , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
19.
Dig Dis Sci ; 64(2): 532-543, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30350242

RESUMO

BACKGROUND: In recent decades, the patterns and trends of gastrointestinal (GI) cancer epidemics in Chinese population have been changing. AIMS: To present the epidemiological trends and geographic distributions of four major GI cancers (esophageal cancer, stomach cancer, liver cancer and colorectal cancer) in China from 2010 to 2014. METHODS: It used standardized data extracted from the National Central Cancer Registry database. RESULTS: The age-standardized incidence rates (ASIR) of esophageal cancer decreased from 16.7 to 12.2 per 100,000 and the age-standardized mortality rates (ASMR) decreased from 12.0 to 8.8 per 100,000. The ASIR and the ASMR of stomach cancer dropped from 23.7 to 19.5 per 100,000 and from 16.6 to 13.3 per 100,000. The ASIR of liver cancer fell from 21.4 to 17.8 per 100,000 and its ASMR fell from 18.4 per 100,000 to 15.3 per 100,000. The ASIR of colorectal cancer increased from 16.1 to 17.5 per 100,000, whereas the ASMR fluctuated between 7.6 and 7.9 per 100,000. Moreover, the incidence and mortality of each cancer differed between males and females, urban and rural residence, as well as various regions. CONCLUSION: From 2010 to 2014, esophageal cancer, stomach cancer and liver cancer showed downward trend, while the ASIR of colorectal cancer slightly rose and its ASMR presented stable.


Assuntos
Adenocarcinoma/epidemiologia , Carcinoma Hepatocelular/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Hepáticas/epidemiologia , Sistema de Registros , Adenocarcinoma/mortalidade , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma de Células Escamosas/mortalidade , China/epidemiologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/mortalidade , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/mortalidade , Feminino , Neoplasias Gastrointestinais/mortalidade , Humanos , Incidência , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , População Rural , Fatores Sexuais , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/mortalidade , População Urbana
20.
Exp Cell Res ; 349(1): 191-197, 2016 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-27780730

RESUMO

Hepatitis B virus (HBV) causes acute and chronic hepatitis, and is one of the major causes of cirrhosis and hepatocellular carcinoma. Accumulating evidence suggests that inflammation is the key factor for liver cirrhosis and hepatocellular carcinoma. MicroRNAs play important roles in many biological processes. Here, we aim to explore the function of microRNAs in the HBX-induced inflammation. First, microarray experiment showed that HBV+ liver samples expressed higher level of miR-203a compared to HBV- liver samples. To verify these alterations, HBx-coding plasmid was transfected into HepG2 cells to overexpress HBx protein. The real-time PCR results suggested that over-expression of HBx could induce up-regulation of miR-203a. To define how up-regulation of miR-203a can induce liver cells inflammation, we over-expressed miR-203a in HepG2 cells. Annexin V staining and BrdU staining suggested that overexpression of miR-203a significantly increased the cell apoptosis and proliferation, meanwhile, over-expression of miR-203a could lead to a decrease in G0/G1 phase cells and an increase in G2/M phase cells. Some cytokines production including IL-6 and IL-8 were significantly increased, but TGFß and IFNγ were decreased in miR-203a over-expressed HepG2 cells. Luciferase reporter assay experiments, protein mass-spectrum assay and real-time PCR all together demonstrated that Rap1a was the target gene of miR-203a. Further experiments showed that these alterations were modulated through PI3K/ERK/p38/NFκB pathways. These data suggested that HBV-infection could up-regulate the expression of miR-203a, thus down regulated the expression of Rap1a and affected the PI3K/ERK/p38/NFκB pathways, finally induced the hepatitis inflammation.


Assuntos
Inflamação/genética , MicroRNAs/metabolismo , Transativadores/metabolismo , Proteínas rap1 de Ligação ao GTP/metabolismo , Apoptose/genética , Ciclo Celular , Proliferação de Células , Citocinas/genética , Citocinas/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Células Hep G2 , Vírus da Hepatite B/fisiologia , Humanos , Inflamação/patologia , Fígado/metabolismo , Fígado/patologia , Fígado/virologia , Sistema de Sinalização das MAP Quinases/genética , MicroRNAs/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Proteínas Virais Reguladoras e Acessórias
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