Development and validation of a prediction model for early screening of people at high risk for colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a serious threat worldwide. Although early screening is suggested to be the most effective method to prevent and control CRC, the current situation of early screening for CRC is still not optimistic. In China, the incidence of CRC in the Yangtze River Delta region is increasing dramatically, but few studies have been conducted. Therefore, it is necessary to develop a simple and efficient early screening model for CRC. AIM: To develop and validate an early-screening nomogram model to identify individuals at high risk of CRC. METHODS: Data of 64448 participants obtained from Ningbo Hospital, China between 2014 and 2017 were retrospectively analyzed. The cohort comprised 64448 individuals, of which, 530 were excluded due to missing or incorrect data. Of 63918, 7607 (11.9%) individuals were considered to be high risk for CRC, and 56311 (88.1%) were not. The participants were randomly allocated to a training set (44743) or validation set (19175). The discriminatory ability, predictive accuracy, and clinical utility of the model were evaluated by constructing and analyzing receiver operating characteristic (ROC) curves and calibration curves and by decision curve analysis. Finally, the model was validated internally using a bootstrap resampling technique. RESULTS: Seven variables, including demographic, lifestyle, and family history information, were examined. Multifactorial logistic regression analysis revealed that age [odds ratio (OR): 1.03, 95% confidence interval (CI): 1.02-1.03, P < 0.001], body mass index (BMI) (OR: 1.07, 95%CI: 1.06-1.08, P < 0.001), waist circumference (WC) (OR: 1.03, 95%CI: 1.02-1.03 P < 0.001), lifestyle (OR: 0.45, 95%CI: 0.42-0.48, P < 0.001), and family history (OR: 4.28, 95%CI: 4.04-4.54, P < 0.001) were the most significant predictors of high-risk CRC. Healthy lifestyle was a protective factor, whereas family history was the most significant risk factor. The area under the curve was 0.734 (95%CI: 0.723-0.745) for the final validation set ROC curve and 0.735 (95%CI: 0.728-0.742) for the training set ROC curve. The calibration curve demonstrated a high correlation between the CRC high-risk population predicted by the nomogram model and the actual CRC high-risk population. CONCLUSION: The early-screening nomogram model for CRC prediction in high-risk populations developed in this study based on age, BMI, WC, lifestyle, and family history exhibited high accuracy.

A platform method for plasmid isoforms analysis by capillary gel electrophoresis.

In the production of novel biological products, plasmids are often engineered into delivery vectors for target genes, which can be used directly as vaccines or as intermediate products for gene/cell therapy. Plasmid DNA exists in several topological forms such as supercoiled, linear, and open circular. As supercoiled plasmid shows the highest efficiency in transfecting eukaryotic cells, the content of supercoiled plasmids becomes an important indicator of plasmid quality. CGE is an effective analysis method for separating different topological structures of plasmids. For the purpose of providing plasmid manufacturers and regulatory agencies with an efficient and readily used tool for monitoring the quality of plasmids, this article identifies the optimal separation and detection conditions of CGE, presents a platform-based plasmid analytical method, and uses plasmid of different sizes to verify the feasibility of this method. In terms of detector, the LIF detector has obvious advantages over the ultraviolet detector in sensitivity and resolution. Using the optimal CE condition (10× gel buffer), baseline separation of different topological forms and impurities can be achieved for different plasmid sizes (5.9, 7.8, 15.4 kb). In addition, 6.5 kb plasmid was used to compare the different separation technologies such as CGE-LIF, ion exchange chromatography and agarose gel electrophoresis. The result shows that CGE-LIF can provide better resolution and quantitation accuracy than ion exchange chromatography and agarose gel electrophoresis. CGE-LIF, as a quick and convenient method to separate and quantify plasmids, has the advantages of high sensitivity, high resolution, and high quantitative accuracy. Therefore, it is ideal for analysis of plasmids with different sizes, and it can also be used as a platform method for manufacturers and regulatory agencies to monitor the purity and stability of plasmids.

Oral Glutamine May Have No Clinical Benefits to Prevent Radiation-Induced Oral Mucositis in Adult Patients With Head and Neck Cancer: A Meta-Analysis of Randomized Controlled Trials.

Objectives: The role of oral glutamine for the management of oral mucositis (OM) has not yet been confirmed. The objective of the present study is to further investigate whether oral glutamine is effective in preventing and treating OM among patients with head and neck cancer (HNC) receiving radiotherapy alone or concurrent with chemotherapy. Methods: A systematic search was performed in PubMed, EMBASE, EBSCO, and Cochrane Central Register of Controlled Trials (CENTRAL) to capture all potential citations from the inception to June 2019. Then data extraction and assessment of risk of bias were carried out after selecting the eligible citations. RevMan 5.3 software was used to perform all statistical analyses. Results: Six randomized controlled trials (RCTs) including 441 patients were included in the final analysis. The meta-analysis showed that oral glutamine couldn't significantly decrease the incidence of OM (risk ratio [RR] = 0.98, 95% confidence interval [CI] = 0.94-1.02) and alleviate the development of moderate or severe grade of OM (Moderate-to-severe OM: RR = 0.81, 95% CI = 0.59-1.12; Severe OM: RR = 0.45, 95% CI = 0.13-1.52). But oral glutamine may have the potential to reduce the opioid use (RR = 0.84, 95% CI = 0.71-0.99). The role of oral glutamine in delaying the onset of OM remains uncertain due to conflicting results between quantitative (mean difference [MD] = 4.11 days, 95% CI = 3.49-4.73) and qualitative results. Conclusions: Oral glutamine may have no clinical benefits to prevent or reduce the incidence and severity of radiation-induced OM in patients with HNC receiving radiotherapy alone or concurrent with chemotherapy. It is also uncertain whether oral glutamine can delay the onset of OM. But it may have the potential to relieve the degree of oral pain. Nevertheless, we must cautiously interpret the results because the observed effect size for delay in mucositis start or reduction in opioid use is marginal. Moreover, further RCTs with more rigorous methodology and large-scale are required to enhance the quality of evidence.

Progressive muscle relaxation is effective in preventing and alleviating of chemotherapy-induced nausea and vomiting among cancer patients: a systematic review of six randomized controlled trials.

PURPOSE: Previous systematic review suggested a beneficial effect of progressive muscle relaxation (PMR) for cancer patients receiving chemotherapy. However, poor quality of eligible studies which included in previous systematic review impaired the reliability and validity of findings. The aim of the present systematic review was to further assess the value of PMR in chemotherapy-induced nausea and vomiting. METHODS: We assigned two independent investigators to search potential studies in PubMed, Cochrane Controlled Register of Trial (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), China Biomedical Literature database (CBM), China National Knowledge Infrastructure (CNKI), and Wanfang Data database. We used data extraction sheet to extract essential information, and used the Cochrane risk of bias assessment tool to appraise the quality of eligible studies. Finally, we qualitatively summarized the results of all included studies. RESULTS: Six studies enrolling 288 patients were included finally. Of these 6 studies, three were labeled as moderate quality and the remaining studies were low quality. All included studies consistently suggested that PMR has a positive effect on chemotherapy-induced nausea and vomiting, especially on the incidence, frequency, and degree of delayed nausea and vomiting. CONCLUSION: Independent studies indicated that PMR was a beneficial approach of preventing and alleviating chemotherapy-induced nausea and vomiting among cancer patients. However, further studies enrolling other types of primary tumors should be designed in order to increase the generality of PMR because studies which were included in the present systematic review mainly considered patients with lung cancer and breast cancer. Moreover, future studies with high quality and large-scale are also warranted in order to address the limitations in the present systematic review such as poor quality and limited data of eligible studies.

Enhanced Patient Education for Colonic Polyp and Adenoma Detection: Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: To improve patients' comprehension of bowel preparation instructions before colonoscopy, enhanced patient education (EPE) such as cartoon pictures or other visual aids, phone calls, mobile apps, multimedia education and social media apps have been proposed. However, it is uncertain whether EPE can increase the detection rate of colonic polyps and adenomas. OBJECTIVE: This meta-analysis aimed to evaluate the efficacy of EPE in detecting colonic polyps and adenomas. METHODS: We searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials from their inception to June 2019 for the identification of trials comparing the EPE with standard patient education for outpatients undergoing colonoscopy. We used a random effects model to calculate summary estimates of the polyp detection rate (defined as the number of patients with at least one polyp divided by the total number of patients undergoing selective colonoscopy), adenoma detection rate (defined as the number of patients with at least one adenoma divided by the total number of patients undergoing selective colonoscopy), advanced adenoma detection rate (defined as the number of patients with at least one advanced adenoma divided by the total number of patients undergoing selective colonoscopy), sessile serrated adenoma detection rate (defined as the number of patients with at least one sessile serrated adenoma divided by the total number of patients undergoing selective colonoscopy), cancer detection rate (defined as the number of patients with at least one cancer divided by the total number of patients undergoing selective colonoscopy), or adenoma detection rate - plus (defined as the number of additional adenomas found after the first adenoma per colonoscopy). Moreover, we conducted trial sequential analysis (TSA) to determine the robustness of summary estimates of all primary outcomes. RESULTS: We included 10 randomized controlled trials enrolling 4560 participants for analysis. The meta-analysis suggested that EPE was associated with an increased polyp detection rate (9 trials; 3781 participants; risk ratio [RR] 1.19, 95% CI 1.05-1.35; P<.05; I2=42%) and adenoma detection rate (5 trials; 2133 participants; RR 1.37, 95% CI 1.15-1.64; P<.001; I2=0%), which were established by TSA. Pooled result from the inverse-variance model illustrated an increase in the sessile serrated adenoma detection rate (3 trials; 1248 participants; odds ratio 1.76, 95% CI 1.22-2.53; P<.05; I2=0%). One trial suggested an increase in the adenoma detection rate - plus (RR 4.39, 95% CI 2.91-6.61; P<.001). Pooled estimates from 3 (1649 participants) and 2 trials (1375 participants) generated no evidence of statistical difference for the advanced adenoma detection rate and cancer detection rate, respectively. CONCLUSIONS: The current evidence indicates that EPE should be recommended to instruct bowel preparation in patients undergoing colonoscopy because it can increase the polyp detection rate, adenoma detection rate, and sessile serrated adenoma detection rate. However, further trials are warranted to determine the efficacy of EPE for advanced adenoma detection rate, adenoma detection rate - plus, and cancer detection rate because of limited data.

Progressive Changes in the Retinal Structure of Patients with Parkinson's Disease.

BACKGROUND: Many optical coherence tomography (OCT) studies have reported alterations in the retinal nerve fiber layer (RNFL) in Parkinson's disease (PD) and other neurodegenerative diseases. However, whether retinal alterations are a biomarker for PD is still controversial. OBJECTIVE: To investigate potential correlations between PD and morphological changes in retina using OCT and to determine its usefulness as a biomarker of disease progression in PD. METHODS: We performed a cross-sectional study on patients with PD (N = 37) and age-matched controls (N = 42), followed by a longitudinal study of the PD patients (N = 22) over approximately 2.5 years. RESULTS: The average retinal nerve fiber layer (RNFL) thickness (p < 0.001), total macular thickness (p = 0.001), and macular volume (p = 0.001) were decreased in PD patients compared to controls and had further decreased at the follow-up visit (p < 0.05 for all). The average RNFL thickness and the total thickness of macular were negatively correlated with age in PD patients at baseline. Linear regression analysis revealed that age (p = 0.002, p = 0.003, respectively) and LEDD (p = 0.011, p = 0.013, respectively) were correlated to total thickness and volume of macular in 22 PD patients in the follow-up study. However, no correlation was found between RNFL and other parameters. CONCLUSIONS: PD progression is associated with pronounced retinal structure changes, which can be quantified by OCT. Patterns of RNFL and macular damage detected by the noninvasive technology of OCT can be a useful biomarker for evaluating the progression of PD.

Lysergic acid diethylamide causes photoreceptor cell damage through inducing inflammatory response and oxidative stress.

Lysergic acid diethylamide (LSD), a classical hallucinogen, was used as a popular and notorious substance of abuse in various parts of the world. Its abuse could result in long-lasting abnormalities in retina and little is known about the exact mechanism. This study was to investigate the effect of LSD on macrophage activation state at non-toxic concentration and its resultant toxicity to photoreceptor cells. Results showed that cytotoxicity was caused by LSD on 661 W cells after co-culturing with RAW264.7 cells. Treatment with LSD-induced RAW264.7 cells to the M1 phenotype, releasing more pro-inflammatory cytokines, and increasing the M1-related gene expression. Moreover, after co-culturing with RAW264.7 cells, significant oxidative stress in 661 W cells treated with LSD was observed, by increasing the level of malondialdehyde (MDA) and reactive oxygen species (ROS), and decreasing the level of glutathione (GSH) and the activity of superoxide dismutase (SOD). Our study demonstrated that LSD caused photoreceptor cell damage by inducing inflammatory response and resultant oxidative stress, providing the scientific rationale for the toxicity of LSD to retina.

Serum sodium and chloride are inversely associated with dyskinesia in Parkinson's disease patients.

Objective: We aim to report and evaluate the associations between serum sodium and chloride and dyskinesia in patients with Parkinson's disease. One hundred and two patients with Parkinson's disease were enrolled in this study. Methods: Patients' serum electrolytes including sodium, calcium, potassium, magnesium, and chloride were measured. Other demographic information was collected, and Unified Parkinson's disease rating scale and Hoehn and Yahr stage scale were also performed. Results: Patients with dyskinesia tended to have longer duration of disease, higher daily levodopa-equivalent dose, and Hoehn-Yahr stage, with lower serum sodium than those without dyskinesia. Spearman correlation analyses showed that serum sodium inversely correlated with duration of disease (r = -.218, p = .028), and positively correlated with serum chloride levels (r = .565, p < .001). Univariate logistic regression analysis found that duration of disease, daily levodopa-equivalent dose, serum sodium, and serum chloride were associated with dyskinesia in Parkinson's disease patients (p < .05 for all). After adjusting for age, sex, age at onset of Parkinson's disease, medical history, and other covariates, serum sodium and chloride were still associated with dyskinesia, with corresponding Odd ratios 0.783 (95% confidence intervals, 0.642-0.955) and 0.796 (95% confidence intervals, 0.652-0.972), respectively. Conclusion: Our findings indicated that serum sodium and chloride levels were inversely associated with dyskinesia in patients with Parkinson's disease. Further studies with large samples and range of serum sodium and chloride are needed.

Therapeutic effects of FuZhiSan on Alzheimer's disease rat model:evaluation with PET imaging / 中华核医学杂志

Objective To assess the feasibility of using PET molecular imaging to evaluate the therapeutic effects of traditional Chinese medicine FuZhiSan (FZS) on the model of aging Alzheimer's disease (AD) rats. Methods Twenty aged AD rats (Sparague-Dawley rats,male) were randomly divided into FZS treated group (n = 10) and control group (n = 10). Another 10 healthy adult rats were as blank controls. Morris water maze record system was used for cognitive function assessment. Before and after FZS treatment 18 F-fluorodeoxyglucose (FDG) and 11 C-2- [4'-(methylamino) phenyl] benzothiazol-6-ol ( PIB )PET imaging was undertaken. After post-treatment imaging procedures the brain tissues of all animals were taken for histochemical study,such as staining with HE,congo red,amyloid β (Aβ) immunofluorescence,5-bromo-2-deoxyuridine (BrdU) immunofluorescence and NeuN immunofluorescence. Paired t-test was performed with SPSS 13.0 software for the data analysis. Results The cognitive dysfunction of aging AD rats was improved after FZS treatment. The escape latency in FZS treated group was significantly shorter than that of control group ((32.5 ±10.8) s vs (102.6±8.8) s,t =15.7987,P=0. 0001). Diffuse neuronal loss and Aβ deposition were detected in the hippocampus and cortex in the aged AD rats. The imaging data showed that brain glucose metabolism was amended in FZS treated group while the abatement of amyloid deposition was not significant. Immunofluorescence results indicated that the neuronal proliferation was more remarkable in FZS treated group. Conclusions It may be feasible to use PET imaging as a method to evaluate the therapeutic effect in AD rats. FZS may ameliorate memory dysfunction of aged AD rats. Its mechanism may be partly contributed to the enhancement of the neuronal proliferation and survival.