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BACKGROUND: Acute bleeding due to esophageal varices (EVs) is a life-threatening complication in patients with cirrhosis. The diagnosis of EVs is mainly through upper gastrointestinal endoscopy, but the discomfort, contraindications and complications of gastrointestinal endoscopic screening reduce patient compliance. According to the bleeding risk of EVs, the Baveno VI consensus divides varices into high bleeding risk EVs (HEVs) and low bleeding risk EVs (LEVs). We sought to identify a non-invasive prediction model based on spleen stiffness measurement (SSM) and liver stiffness measurement (LSM) as an alternative to EVs screening. AIM: To develop a safe, simple and non-invasive model to predict HEVs in patients with viral cirrhosis and identify patients who can be exempted from upper gastrointestinal endoscopy. METHODS: Data from 200 patients with viral cirrhosis were included in this study, with 140 patients as the modelling group and 60 patients as the external validation group, and the EVs types of patients were determined by upper gastrointestinal endoscopy and the Baveno VI consensus. Those patients were divided into the HEVs group (66 patients) and the LEVs group (74 patients). The effect of each parameter on HEVs was analyzed by univariate and multivariate analyses, and a non-invasive prediction model was established. Finally, the discrimination ability, calibration ability and clinical efficacy of the new model were verified in the modelling group and the external validation group. RESULTS: Univariate and multivariate analyses showed that SSM and LSM were associated with the occurrence of HEVs in patients with viral cirrhosis. On this basis, logistic regression analysis was used to construct a prediction model: Ln [P/(1-P)] = -8.184 -0.228 × SSM + 0.642 × LSM. The area under the curve of the new model was 0.965. When the cut-off value was 0.27, the sensitivity, specificity, positive predictive value and negative predictive value of the model for predicting HEVs were 100.00%, 82.43%, 83.52%, and 100%, respectively. Compared with the four prediction models of liver stiffness-spleen diameter to platelet ratio score, variceal risk index, aspartate aminotransferase to alanine aminotransferase ratio, and Baveno VI, the established model can better predict HEVs in patients with viral cirrhosis. CONCLUSION: Based on the SSM and LSM measured by transient elastography, we established a non-invasive prediction model for HEVs. The new model is reliable in predicting HEVs and can be used as an alternative to routine upper gastrointestinal endoscopy screening, which is helpful for clinical decision making.
Subject(s)
Elasticity Imaging Techniques , Esophageal and Gastric Varices , Humans , Esophageal and Gastric Varices/diagnostic imaging , Esophageal and Gastric Varices/etiology , Spleen/diagnostic imaging , Spleen/pathology , Liver Cirrhosis/diagnosis , Liver Cirrhosis/diagnostic imaging , HemorrhageABSTRACT
Zinc finger protein 671 (ZNF671) has been described as a vital cancer inhibitor in multiple neoplasms, yet the functional roles of ZNF671 in colorectal carcinoma (CRC) remain unresolved. This project examined the possible link between ZNF671 and CRC. Lower levels of ZNF671 were observed in CRC tissue compared with noncancerous tissue, which were related to a worse survival rate in CRC patients. High methylation levels at the ZNF671 gene promoter region were shown in CRC tissue, which were inversely correlated with ZNF671 expression. Treatment with demethylation agents restored ZNF671 levels in CRC cell lines. Up-regulation of ZNF671 resulted in suppressive effects on the proliferative ability and metastatic potency of CRC cells. Moreover, the up-regulation of ZNF671 reinforced the chemosensitivity of CRC cells. A mechanism study determined ZNF671 to be a vital mediator of Notch signaling. The up-regulation of ZNF671 decreased the expression of Notch1 and lowered the levels of NICD, HES1, and HEY1. The overexpression of NICD1 diminished ZNF671-mediated antitumor effects. ZNF671 depletion reinforced Notch signaling, and Notch suppression reversed ZNF671-depletion-elicited protumor effects. Moreover, the overexpression of ZNF671 weakened the tumorigenicity of CRC cells in a xenograft model in vivo. In summary, ZNF671 exerts a cancer-inhibiting function in CRC via the deactivation of Notch signaling. Low ZNF671 levels caused by gene promoter hypermethylation contribute to the malignant transformation of CRC. This work underlines the interest of ZNF671 as a target candidate for exploiting novel anti-CRC therapies.
Subject(s)
Colorectal Neoplasms , Humans , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , DNA Methylation , Signal Transduction , Zinc Fingers , Gene Expression Regulation, Neoplastic , Cell Line, Tumor , Tumor Suppressor Proteins/metabolismABSTRACT
BACKGROUND: Fracture nonunion/delayed union seriously affects physical and mental health and quality of life. The aim of this study was to evaluate the relative efficacy of different adjuvant treatments for nonunion/delayed union by network meta-analysis. METHODS: A comprehensive search was performed to identify randomized controlled trials (RCTs) evaluating adjuvant treatment in the management of nonunion/delayed union. A network meta-analysis reporting on healing rate, healing time, and adverse effect (AE) outcomes was conducted to assess and compare different interventions. RESULTS: Thirty studies were included in the analysis. For the healing rate outcome, bone marrow aspirate (BMA) + autologous cancellous bone (ACB) was found to be significantly better than ACB alone (odds ratio: 0.12; 95% confidence interval: 0.03, 0.59). In the ranking results, BMA+ platelet-rich plasma (PRP) (96%), BMA + ACB (90%), and BMA alone (82%) showed relative advantages in the healing rate. Low-intensity pulsed ultrasonography (LIUS) intervention significantly shortened the healing time compared with ACB (SMD: -9.26; 95% CI: - 14.64, - 3.87). LIUS (100%), BMA + PRP (74%), and bone morphogenetic proteins (BMPs) (69%) have relative advantages. Compared with the control, electromagnetic field (EMF) (OR: 13.21; 95% CI: 1.58, 110.40) and extracorporeal shock wave (ESWT) (OR: 4.90; 95% CI: 1.38, 17.43) had a higher AE risk. CONCLUSIONS: Among the current intervention strategies, BMA in combination with PRP and ACB can improve the healing rate of nonunion/delayed union. LIUS can significantly shorten the healing time. EMF and ESWT may have a high risk of AE. However, large-scale, well-designed studies are still needed to confirm the results. TRIAL REGISTRATION: Retrospectively registered.
Subject(s)
Fractures, Ununited , Platelet-Rich Plasma , Fracture Healing , Fractures, Ununited/diagnostic imaging , Fractures, Ununited/therapy , Humans , Network Meta-Analysis , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
Background Overweight/obesity in children are a global health issue. Preschool age is an important stage of children's growth and development and dietary behaviors, so it is crucial to explore dietary behavior characteristics and childhood overweight/obesity. Objective To explore the association between dietary behavior characteristics and overweight/obesity in preschool children in Shanghai, and the consistency of children's eating behavior characteristics with their parents'. Methods The children aged 3 to 6 years in 5 kindergartens in Shanghai in 2015 were selected by convenience sampling and surveyed. Their height and weight were measured. Children's and parents' dietary behavior characteristics were self-reported by their parents. According to the weight-for-height recommended by the World Health Organization, excess weight was calculated by the following formula: excess-weight%=[(measured weight - standard weight)/standard weight×100%]; obese is determined at excess-weight% > 20%, overweight: excess-weight% at 10%-20%, normal weight: excess-weight% at −10%-<10%. Chi-squared test and t test were used to compare the differences of demographic and dietary behavior characteristics between overweight/obese and normal weight children. Multiple logistic regression models were used to evaluate the association between dietary behaviors and overweight/obesity. The consistency of dietary behavior characteristics was tested between children and their parents. Results Among the 897 preschool children, 217 (24.2%) were overweight/obese and 680 (75.8%) were of normal weight. The birth weight [(3439±472) g vs. (3361±418) g] and proportion of monthly household income < 10000 yuan (17.1% vs. 10.7%) in the overweight/obese children were significantly higher than those in the normal weight children, and there were no statistical differences in sex, age, gestational age, time of adding complementary foods, outdoor activities after school every day, and parental BMI. After adjusting for potential confounders such as sex, age, household income, outdoor activities after school every day, and parental overweight/obesity, frequently having puffed food (OR=2.46, 95%CI: 1.20-4.95), western-style fast food (OR=3.52, 95%CI: 1.41-8.79), and carbonated drinks (OR=2.92, 95%CI: 1.37-6.13), often eating a lot (OR=1.51, 95%CI: 1.09-2.08) and having a good appetite (OR=2.60, 95%CI: 1.87-3.62), having regular meals (OR=1.48, 95%CI: 1.07-2.03), and fast eating (OR=3.37, 95%CI: 2.10-5.42) were positively associated with children's overweight/obesity (P<0.05). Children's partial/picky eating was inconsistent with fathers' behavior (P<0.05), while the other dietary behaviors were similar with both mothers' and fathers'. Conclusion Eating behavior characteristics of preschool children are associated with overweight/obesity, and affected by their parents. Early identifying dietary behavior problems and improving dietary habits of children might be an effective strategy in preventing and controlling the occurrence and development of obesity in childhood.
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Hepatocellular carcinoma (HCC) is typically fatal, and patients with hepatocellular carcinoma are usually diagnosed at the late stages. Although the treatments for HCC have been rapidly advancing, novel targets for HCC are still desperately needed, especially for targeted therapies. Here, we identified an enriched long non-coding RNA, AC006262.5, associated with HCC, that promoted the proliferation, migration, and invasiveness of HCC cells, both in vitro and in vivo. In addition, our results revealed that AC006262.5 bound to and regulated miR-7855-5p, a tumor-suppressive miRNA, in HCC. Moreover, our data show that AC006262.5 regulates the expression of BPY2C via miR-7855-5p. Finally, we found that AC006262.5 and miR-7855-5p formed a regulatory loop. Upregulation of AC006262.5 resulted in decreased expression of miR-7855-5p, and downregulation of miR-7855-5p further facilitated the expression of AC006262.5. Our work provides novel targets for HCC diagnosis and treatment, and sheds light on the lncRNA-miRNA regulatory nexus that controls the pathology of HCC.
Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/pathology , Cell Movement , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Proteins/metabolism , RNA, Long Noncoding/genetics , Animals , Apoptosis , Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Cell Proliferation , Humans , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Mice , Mice, Inbred BALB C , Mice, Nude , Proteins/genetics , Tumor Cells, Cultured , Xenograft Model Antitumor AssaysABSTRACT
BACKGROUND: This study will investigate the effectiveness of and safety of social skills intervention (SSI) for the management of children with autism spectrum disorder (ASD). METHODS: All potential randomized controlled trials related to the effectiveness and safety of SSI for children with ASD will be retrieved from Cochrane Library, MEDLINE, EMBASE, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. All these databases will be identified from inception to the present with no limitations of language and publication time. Two investigators will independently perform selection of study, data collection, and study quality assessment, respectively. A third investigator will help to solve any different views between 2 investigators. RevMan 5.3 software will be used for data pooling and statistical analysis. RESULTS: This study will provide synthesis of present evidence on assessing the effectiveness and safety of SSI for children with ASD. CONCLUSION: This study will provide helpful references for the effectiveness and safety of SSI on the management of ASD, which may benefit both patients and clinicians. STUDY REGISTRATION NUMBER: INPLASY202040090.
Subject(s)
Autism Spectrum Disorder/therapy , Social Skills , Humans , Randomized Controlled Trials as Topic , Research Design , Meta-Analysis as TopicABSTRACT
Recent studies have demonstrated that various long non-coding RNAs (lncRNAs) participate in the gastric cancer (GC) development and metastasis. Some lncRNAs exert their regulatory function by interacting with microRNAs. Here we identified a novel lncRNA RP11-81H3.2 that was highly expressed in the GC tissue and cell lines. RP11-81H3.2 knockdown significantly inhibited the proliferation, migration, and invasion of GC cells. Mechanistically, we demonstrated that RP11-81H3.2 directly interacted with miR-339 while miR-339 regulated the HNRNPA1 expression by targeting HRRNPA1 3'-UTR. RP11-81H3.2-miR-339-HNRNPA1 interaction network regulated the GC cell proliferation, migration, and invasion. Moreover, our results confirmed that RP11-81H3.2 knockdown suppressed the tumor growth of GC in a xenograft model in vivo. In summary, the results suggest that RP11-81H3.2 functions as an oncogene in GC and could be utilized as a promising diagnosis and therapeutic marker for GC treatment.
Subject(s)
Biomarkers, Tumor/metabolism , Gene Expression Regulation, Neoplastic , Heterogeneous Nuclear Ribonucleoprotein A1/metabolism , MicroRNAs/genetics , RNA, Long Noncoding/genetics , Stomach Neoplasms/pathology , Animals , Apoptosis , Biomarkers, Tumor/genetics , Cell Movement , Cell Proliferation , Female , Heterogeneous Nuclear Ribonucleoprotein A1/genetics , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Nude , MicroRNAs/metabolism , Middle Aged , Prognosis , Protein Interaction Domains and Motifs , RNA, Long Noncoding/metabolism , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Survival Rate , Tumor Cells, Cultured , Xenograft Model Antitumor AssaysABSTRACT
As a relay center between the cerebral cortex and various subcortical brain areas, the thalamus is repeatedly associated with the dysfunction of brain-gut interaction in patients with irritable bowel syndrome (IBS). However, the regional morphological alterations of the thalamus in IBS are not well defined. We acquired structural magnetic resonance data from 34 patients with IBS and 34 demographically similar healthy subjects. Data processing was performed using FMRIB's Integrated Registration and Segmentation Tool (FIRST). Volumetric analysis and surface-based vertex analysis were both carried out to characterize the morphology of the thalamus and other subcortical structures. Our results suggested that the majority (31 cases) of the patients with IBS had diarrhea-predominant symptoms. Volumetric analysis revealed a larger normalized volume of the right thalamus and left caudate nucleus in patients with IBS than in healthy controls. Surface analysis indicated that the difference arose mainly from the laterodorsal nucleus of the right thalamus, and the body of the left caudate nucleus. In addition, patients with IBS had different hemispheric asymmetries of the thalamus (rightward) and caudate nucleus (leftward) from controls (leftward for the thalamus and rightward for the caudate nucleus). In general, our results indicated that patients with diarrhea-predominant IBS had enlarged thalamus and caudate nucleus volumes, as well as altered hemispheric asymmetries of these two structures, compared with healthy controls. The neuroimaging evidence of these structural alterations helps clarify the underlying pathophysiology of diarrhea-predominant IBS.
Subject(s)
Diarrhea , Irritable Bowel Syndrome , Thalamus , Cross-Sectional Studies , Diarrhea/diagnostic imaging , Diarrhea/pathology , Humans , Irritable Bowel Syndrome/diagnostic imaging , Irritable Bowel Syndrome/pathology , Magnetic Resonance Imaging , Thalamus/diagnostic imaging , Thalamus/pathologyABSTRACT
AIM: To study the evolution of gastrointestinal symptoms and associated factors in Chinese patients with functional dyspepsia (FD). METHODS: From June 2008 to November 2009, a total of 1049 patients with FD (65.3% female, mean age 42.80 ± 11.64 years) who visited the departments of gastroenterology in Wuhan, Beijing, Shanghai, Guangzhou, and Xi'an, China were referred for this study. All of the patients fulfilled the Rome III criteria for FD. Baseline demographic data, dyspepsia symptoms, anxiety, depression, sleep disorder, and drug treatment were assessed using self-report questionnaires. Patients completed questionnaires at baseline and after 1, 3, 6 and 12 mo follow-up. Comparison of dyspepsia symptoms between baseline and after follow-up was explored using multivariate analysis of variance of repeated measuring. Multiple linear regression was done to examine factors associated with outcome, both longitudinally and horizontally. RESULTS: Nine hundred and forty-three patients (89.9% of the original population) completed all four follow-ups. The average duration of follow-up was 12.24 ± 0.59 mo. During 1-year follow-up, the mean dyspeptic symptom score (DSS) in FD patients showed a significant gradually reduced trend (P < 0.001), and similar differences were found for all individual symptoms (P < 0.001). Multiple linear regression analysis showed that sex (P < 0.001), anxiety (P = 0.018), sleep disorder at 1-year follow-up (P = 0.019), weight loss (P < 0.001), consulting a physician (P < 0.001), and prokinetic use during 1-year follow-up (P = 0.035) were horizontally associated with DSS at 1-year follow-up. No relationship was found longitudinally between DSS at 1-year follow-up and patient characteristics at baseline. CONCLUSION: Female sex, anxiety, and sleep disorder, weight loss, consulting a physician and prokinetic use during 1-year follow-up were associated with outcome of FD.
Subject(s)
Dyspepsia/diagnosis , Adult , Anxiety/epidemiology , China/epidemiology , Dyspepsia/drug therapy , Dyspepsia/epidemiology , Female , Gastrointestinal Agents/therapeutic use , Humans , Linear Models , Longitudinal Studies , Male , Middle Aged , Multivariate Analysis , Prognosis , Risk Factors , Sex Factors , Sleep Wake Disorders/epidemiology , Surveys and Questionnaires , Time Factors , Weight LossABSTRACT
Objective To explore the effect and heaviness of smoking on the routine parameters of semen quality.Methods A total of 727 eligible subjects including 421 smokers and 306 nonsmokers were selected in 2004-2006 in Hebei,Shanxi,Guizhou,Zhejiang and Shandong provinces.Data on background information,general demographic characteristics,exposure to smoking and related confounding factors were obtained through a questionnaire survey.Semen samples of all the subjects were collected during the period of study.Parameters of semen were examined according to the manual recommended by WHO.Results Four models from the multiple logistic regression regarding the semen routine parameters were used as the dependent variables to be fitted in descending order respectively,while six confounders including area,age,abstinence time,education level,history of alcohol intake and the exposure to pesticides atc.,were adjusted.Results showed that smoking could affect the sperm viability,with significantly higher proportion of abnormal sperm viability seen in the smoking group (OR= 1.77,95% CI:1.12-2.80).Proportions regarding the abnormal mobility and morphology of sperms in the smoking group were also significantly higher than in the control group,with OR values as 1.51 (95%CI:1.00-2.27) and 2.55 (95%CI:1.68-3.88) respectively.The density of sperms was significantly decreased in the smoking groups who smoked more than 20 cigarettes per day (OR= 1.70,95%CI:1.05-2.76) or the total numbers of cigarette consumption exceeding 150 000(OR=1.84,95%CI:1.03-3.29).Conclusion Smoking showed adverse effects on the quality of semens,especially for heavy or long-term smokers.
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Objective To explore the effects of high birth weight (HBW) on blood pressure (BP) during childhood.Methods A total of 1435 couples with high or normal birth weight were selected from a birth cohort who were born between 1993 and 1995 in Wuxi,China and,followed between 2005 and 2007.A questionnaire survey was conducted,with their height,weight and blood pressure measured.Results The medians of systolic blood pressure (SBP) and diastolic BP (DBP)of HBW group were 100 mm Hg (Q1-Q3∶90-110 mm Hg),64 mm Hg (Q1-Q3∶60-70 mm Hg) in the high birth weight group,respectively,while they were 100 mm Hg (Q1-Q3∶90-108 mm Hg),62 mm Hg (Q1-Q3∶60-70 mm Hg) in the normal weight group.No statistical significant difference was found between the exposed and unexposed groups.The proportion of elevated BP,including prehypertension and hypertension,in exposed group was 13.66%,a bit higher than that (11.57%) of the unexposed group (P = 0.055).The relative risk (RR) of HBW on elevated BP was 1.06 (0.92-1.21),after adjusted the following parameters as BMI in childhood,sex,age during the follow-up period,age of mother at delivery,gestational age,type of feeding at infancy,dietary habit as well as the frequencies of exercise during childhood.Conclusion No statistically significant correlation was found between high birth weight and blood pressure of children.
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AIM: To investigate whether down-regulation of peroxiredoxin 1 (Prx1) and/or peroxiredoxin 5 (Prx5) sensitizes human esophageal cancer cells to ionizing radiation (IR). METHODS: Human esophageal carcinoma cell lines Eca-109 and TE-1 were used. Prx mRNA expression profiles in Eca-109 and TE-1 cells were determined using RT-PCR. Two highly expressed isoforms of Prxs, Prx1 and Prx5, were silenced by RNA interference (RNAi). Following IR, intracellular reactive oxygen species (ROS) and apoptosis were measured using flow cytometry, the activities of catalase, superoxide dismutase and glutathione peroxidase were measured, and the radiosensitizing effect of RNAi was observed. Tumor xenograft model was also used to examine the radiosensitizing effect of RNAi in vivo. RESULTS: Down-regulation of Prx1 and/or Prx5 by RNAi does not alter the activities of catalase, superoxide dismutase and glutathione peroxidase, but made human tumor cells more sensitive to IR-induced apoptosis both in vitro and in vivo. When the two isoforms were decreased simultaneously, intracellular ROS and apoptosis significantly increased after IR. CONCLUSION: Silencing Prx1 and/or Prx5 by RNAi sensitizes human Eca-109 and TE-1 cells to IR, and the intracellular ROS accumulation may contribute to the radiosensitizing effect of the RNAi.
Subject(s)
Esophageal Neoplasms/genetics , Gene Silencing , Homeodomain Proteins/genetics , Reactive Oxygen Species/metabolism , Animals , Base Sequence , DNA Primers , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/pathology , Humans , Male , Mice , Mice, Inbred BALB C , Radiation, IonizingABSTRACT
Objective To explore the genotoxicity of formaldehyde to mice.Methods Mice were exposed to formaldehyde of several concentrations(1.25,0.50,and 5.00 mg/m3) in the toxicant exposure chamber,2 h/d for 15 consecutive days.Bone marrow micronuclei test and single cell gel electrophoresis were employed to test the genotoxicity.Results Compared with the control group,a significant increase in the rate of micronuclei and the DNA damage of peripheral lymphocytes in experimental groups were found.As to the rate of micronuclei and DNA damage,an obvious dose-effect relationship was showed.Conclusion Formaldehyde has a genotoxic effect for mice,much more attention should be paid in this research field.