A noninvasive multianalytical approach establishment for risk assessment and gastric cancer screening.

Effective screening and early detection are critical to improve the prognosis of gastric cancer (GC). Our study aims to explore noninvasive multianalytical biomarkers and construct integrative models for preliminary risk assessment and GC detection. Whole genomewide methylation marker discovery was conducted with CpG tandems target amplification (CTTA) in cfDNA from large asymptomatic screening participants in a high-risk area of GC. The methylation and mutation candidates were validated simultaneously using one plasma from patients at various gastric lesion stages by multiplex profiling with Mutation Capsule Plus (MCP). Helicobacter pylori specific antibodies were detected with a recomLine assay. Integrated models were constructed and validated by the combination of multianalytical biomarkers. A total of 146 and 120 novel methylation markers were found in CpG islands and promoter regions across the genome with CTTA. The methylation markers together with the candidate mutations were validated with MCP and used to establish a 133-methylation-marker panel for risk assessment of suspicious precancerous lesions and GC cases and a 49-methylation-marker panel as well as a 144-amplicon-mutation panel for GC detection. An integrated model comprising both methylation and specific antibody panels performed better for risk assessment than a traditional model (AUC, 0.83 and 0.63, P < .001). A second model for GC detection integrating methylation and mutation panels also outperformed the traditional model (AUC, 0.82 and 0.68, P = .005). Our study established methylation, mutation and H. pylori-specific antibody panels and constructed two integrated models for risk assessment and GC screening. Our findings provide new insights for a more precise GC screening strategy in the future.

Synthesis of Low-Cost and High-Performance Dual-Atom Doped Carbon-Based Materials with a Simple Green Route as Anodes for Sodium-Ion Batteries.

Sodium-ion batteries (SIBs) are promising alternatives to replace lithium-ion batteries as future energy storage batteries because of their abundant sodium resources, low cost, and high charging efficiency. In order to match the high energy capacity and density, designing an atomically doped carbonous material as the anode is presently one of the important strategies to commercialize SIBs. In this work, we report the preparation of high-performance dual-atom-doped carbon (C) materials using low-cost corn starch and thiourea (CH4N2S) as the precursors. The electronegativity and radii of the doped atoms and C are different, which can vary the embedding properties of sodium ions (Na+) into/on C. As sulfur (S) can effectively expand the layer spacing, it provides more channels for embedding and de-embedding Na+. The synergistic effect of N and S co-doping can remarkably boost the performance of SIBs. The capacity is preserved at 400 mAh g -1 after 200 cycles at 500 mA g-1; more notably, the initial Coulombic efficiency is 81%. Even at a high rate of high current of 10 A g-1, the cell capacity can still reach 170 mAh g-1. More importantly, after 3000 cycles at 1 A g-1, the capacity decay is less than 0.003% per cycle, which demonstrates its excellent electrochemical performance. These results indicate that high-performance carbon materials can be prepared using low-cost corn starch and thiourea.

Relationship between multi-slice computed tomography features and pathological risk stratification assessment in gastric gastrointestinal stromal tumors.

BACKGROUND: Computed tomography (CT) imaging features are associated with risk stratification of gastric gastrointestinal stromal tumors (GISTs). AIM: To determine the multi-slice CT imaging features for predicting risk stratification in patients with primary gastric GISTs. METHODS: The clinicopathological and CT imaging data for 147 patients with histologically confirmed primary gastric GISTs were retrospectively analyzed. All patients had received dynamic contrast-enhanced CT (CECT) followed by surgical resection. According to the modified National Institutes of Health criteria, 147 lesions were classified into the low malignant potential group (very low and low risk; 101 lesions) and high malignant potential group (medium and high-risk; 46 lesions). The association between malignant potential and CT characteristic features (including tumor location, size, growth pattern, contour, ulceration, cystic degeneration or necrosis, calcification within the tumor, lymphadenopathy, enhancement patterns, unenhanced CT and CECT attenuation value, and enhancement degree) was analyzed using univariate analysis. Multivariate logistic regression analysis was performed to identify significant predictors of high malignant potential. The receiver operating curve (ROC) was used to evaluate the predictive value of tumor size and the multinomial logistic regression model for risk classification. RESULTS: There were 46 patients with high malignant potential and 101 with low-malignant potential gastric GISTs. Univariate analysis showed no significant differences in age, gender, tumor location, calcification, unenhanced CT and CECT attenuation values, and enhancement degree between the two groups (P > 0.05). However, a significant difference was observed in tumor size (3.14 ± 0.94 vs 6.63 ± 3.26 cm, P < 0.001) between the low-grade and high-grade groups. The univariate analysis further revealed that CT imaging features, including tumor contours, lesion growth patterns, ulceration, cystic degeneration or necrosis, lymphadenopathy, and contrast enhancement patterns, were associated with risk stratification (P < 0.05). According to binary logistic regression analysis, tumor size [P < 0.001; odds ratio (OR) = 26.448; 95% confidence interval (CI): 4.854-144.099)], contours (P = 0.028; OR = 7.750; 95%CI: 1.253-47.955), and mixed growth pattern (P = 0.046; OR = 4.740; 95%CI: 1.029-21.828) were independent predictors for risk stratification of gastric GISTs. ROC curve analysis for the multinomial logistic regression model and tumor size to differentiate high-malignant potential from low-malignant potential GISTs achieved a maximum area under the curve of 0.919 (95%CI: 0.863-0.975) and 0.940 (95%CI: 0.893-0.986), respectively. The tumor size cutoff value between the low and high malignant potential groups was 4.05 cm, and the sensitivity and specificity were 93.5% and 84.2%, respectively. CONCLUSION: CT features, including tumor size, growth patterns, and lesion contours, were predictors of malignant potential for primary gastric GISTs.

[Lean strategy for data mining and continuous improvement of Chinese pharmaceutical process: a case study of sporoderm-removal Ganoderma lucidum spore powder].

In the digital transformation of Chinese pharmaceutical industry, how to efficiently govern and analyze industrial data and excavate the valuable information contained therein to guide the production of drug products has always been a research hotspot and application difficulty. Generally, the Chinese pharmaceutical technique is relatively extensive, and the consistency of drug quality needs to be improved. To address this problem, we proposed an optimization method combining advanced calculation tools(e.g., Bayesian network, convolutional neural network, and Pareto multi-objective optimization algorithm) with lean six sigma tools(e.g., Shewhart control chart and process performance index) to dig deeply into historical industrial data and guide the continuous improvement of pharmaceutical processes. Further, we employed this strategy to optimize the manufacturing process of sporoderm-removal Ganoderma lucidum spore powder. After optimization, we preliminarily obtained the possible interval combination of critical parameters to ensure the P_(pk) values of the critical quality properties including moisture, fineness, crude polysaccharide, and total triterpenes of the sporoderm-removal G. lucidum spore powder to be no less than 1.33. The results indicate that the proposed strategy has an industrial application value.

[Pollution Characteristics and Ecological Risk Assessment of Antibiotics in Vegetable Field in Kaizhou, Chongqing].

The accumulation of antibiotics in farmland and its ecological risk have become a research hotspot at home and abroad. The objective of this study was to investigate the occurrence and accumulation of antibiotics and their potential environmental and ecological risks in vegetable fields in Kaizhou district of Chongqing country. The occurrence characteristics of antibiotics including tetracyclines, sulfonamides, quinolones, macrolides, and chloramphenicols were detected using experimental analysis. The results showed that there was an accumulation of antibiotics in the vegetable soil, and 18 antibiotics in five categories were detected (0-42.88 µg·kg-1), mainly for tetracyclines and quinolones. The detection rate of quinolone antibiotics was the highest (15.38%-100%), especially for norfloxacin and ofloxacin (100%), whereas the tetracyclines presented the highest concentration (0-42.88 µg·kg-1). The amount of total antibiotics in the vegetable soil was 1.64-233.11 µg·kg-1, whereas different vegetable soils showed the following trend:water spinach soil (89.73 µg·kg-1)>cabbage soil (32.53 µg·kg-1)>pepper soil (32.16 µg·kg-1)>tomato soil (32.13 µg·kg-1)>cucumber soil (26.46 µg·kg-1)>grassland (7.32 µg·kg-1). The correlation results showed that there was a significantly positive correlation between total antibiotic residues and organic fertilizer application (P<0.05) but a significantly negative correlation with soil pH (P<0.05). Quinolones and sulfonamides were negatively correlated with soil water content (P<0.05), whereas quinolones positively correlated with soil available phosphorus and organic matter content (P<0.05). The potential eco-environmental risk assessment results showed that tetracyclines and quinolones in vegetable soil in Kaizhou district had certain ecological risks, of which 62%-92% and 62%-100% of soil samples with quinolones had potential toxicity to soil animals and microorganisms.

[Preliminary study on the existing problems in health economic evaluation study of acupuncture in China].

The literature of health economic evaluation study in the field of acupuncture in China was systematically summarized and analyzed, and the existing problems in the current research were discussed from the aspects of research perspective, cost calculation scope, data analysis method selection. Moreover, the key points of the health economic evaluation research were summarized, and the research objectives, the relationship between the expected research results and data analysis methods and the process of thinking were sorted out, and several suggestions for research report writing were proposed, aiming to provide a reference for the quality improvement of the acupuncture health economic evaluation research in China.

Influencing factors of resource utilisation in haemodialysis patients-Based on socioecological pyramid model.

AIMS AND OBJECTIVES: To describe the current situation and analyse influencing factors of resource utilisation in maintenance haemodialysis patients. BACKGROUND: The self-management level of patients undergoing maintenance haemodialysis in China is low. The applicability of the Chronic Illness Resources Survey in Chinese maintenance haemodialysis patients has been validated, and this survey can be used to assess the utilisation of self-management support resources among haemodialysis patients. Determining the influencing factors of resource utilisation can help improve the self-management behaviour of haemodialysis patients and control the progression of the disease. DESIGN: A descriptive study design was chosen. METHODS: A convenience sample of 314 patients undergoing haemodialysis was recruited from dialysis centres in three hospitals in western Xinjiang from June 2018-April 2019. SPSS19.0 software was used to describe the current situation of resource utilisation. Moreover, t test, analysis of variance and multivariate linear regression were applied to explore the influencing factors of patients' resource utilisation. Standards for observational studies STROBE Statement checklist-v4 were chosen on reporting the study process. RESULTS: The average score of the total resource utilisation was 2.95 ± 0.51. The average item score of seven dimensions from high to low was 3.46 for medical staff, 3.32 for personal, 3.22 for family and friends, 3.16 for work-related, 3.12 for media policy, 2.55 for neighbourhood/community and 2.23 for organisation. Multiple linear regression showed that there have six main factors, which explained 65.4% of the variance of haemodialysis patients' resource utilisation. CONCLUSIONS: The personal, family and friends, work and media and policy subscales were rated the highest, with support from neighbourhood/community and organisation rated the lowest. In general, participants perceived moderate levels of support. Government and healthcare team should pay more attention on haemodialysis patients who had low level of education, poor economic conditions and poor mental condition. RELEVANCE TO CLINICAL PRACTICE: ESRD has caused a burden on healthcare expenditure and has become a critical public health problem worldwide. Self-management is particularly important for dialysis patients which have attracted extensive interest. In the future research, we can use this questionnaire to evaluate the related resources of disease management of dialysis patients, encourage patients to make full use of the resources around them and focus on those patients with low education and monthly income level and bad mental state.

Evaluation of bioequivalence between generic and brand-name clozapine in Chinese schizophrenic patients: A randomized, two-period, crossover study.

OBJECTIVE: Clozapine is the most effective therapy for schizophrenia. This study compared the bioequivalence of a generic formulation of clozapine (ChangZhou Pharmaceutical Factory Co. Ltd. Jiangsu, China) to the brand name formulation (Clozaril, HLS Therapeutics, Inc., Philadelphia, PA, USA) after multiple doses in Chinese schizophrenic patients. MATERIALS AND METHODS: This was a randomized, open-label, multiple-dose, 2-way crossover study in which patients with schizophrenia received the generic clozapine or Clozaril 100 mg twice daily for 10 days before crossing over to the alternate formulation for the next 10 days. Blood samples were collected at regular intervals during each treatment period, and plasma concentration of clozapine was determined by high-performance liquid chromatography. RESULTS: 26 patients were enrolled, of whom 24 completed the study and were included in the steady-state analyses. The mean AUC0-12 was 6,003.29 h×ng/mL for generic clozapine and 6,347.53 h×ng/mL for Clozaril. The mean Cmax,ss was 698.52 ng/mL for generic clozapine and 739.75 ng/mL for Clozaril. The ratio of the adjusted geometric means and its 90% CI of the ratios for AUC0-12 was 96.24% (89.60 - 103.36%), and for Cmax,ss was 95.90% (88.91 - 103.44%). A total of 66 adverse events were reported by 22 (84.62%) subjects. Among them, 34 occurred in 17 (65.38%) patients during dosing of generic clozapine, and 32 occurred in 16 (61.54%) patients during dosing of brand-name clozapine. CONCLUSION: The result demonstrated that the generic clozapine was bioequivalent to brand-name clozapine (Clozaril). This would provide physicians with reassurance that patients who receive the studied generic clozapine will achieve similar plasma drug concentrations to those of brand-name clozapine (Clozaril).

Establishment and assessment of the hepatic venous pressure gradient using biofluid mechanics (HVPGBFM): protocol for a prospective, randomised, non-controlled, multicentre study.

INTRODUCTION: Portal hypertension (PH) is a severe disease with a poor outcome. Hepatic venous pressure gradient (HVPG), the current gold standard to detect PH, is available only in few hospitals due to its invasiveness and technical difficulty. This study aimed to establish and assess a novel model to calculate HVPG based on biofluid mechanics. METHODS AND ANALYSIS: This is a prospective, randomised, non-controlled, multicentre trial. A total of 248 patients will be recruited in this study, and each patient will undergo CT, blood tests, Doppler ultrasound and HVPG measurement. The study consists of two independent and consecutive cohorts: original cohort (124 patients) and validation cohort (124 patients). The researchers will establish and improve the HVPG using biofluid mechanics (HVPGBFM)model in the original cohort and assess the model in the validation cohort. ETHICS AND DISSEMINATION: The study was approved by the Scientific Research Projects Approval Determination of Independent Ethics Committee of Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (approval number 2017-430 T326). Study findings will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT03470389.

[UPLC fingerprint combined with quantitative analysis of multi-components by single marker for quality assessment of Danshen Injection].

Testing and analysis of chemical markers is currently the prevailing approach for quality assessment of traditional Chinese medicines. However,several important issues remain to be addressed,including the trade-off between accuracy and coverage. In this study,in order to give full play to the advantages of their respective methods and provide technical support for more comprehensively and rapidly evaluate the quality of Danshen Injection products,a fingerprint method was coupled with quantitative analysis of multicomponents by single marker( QAMS),with Danshen Injection as the carrier. Ultra performance liquid chromatography( UPLC) was used to establish the quantitative fingerprint. The UPLC fingerprints contained 13 common peaks,11 of which were identified by using ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry( UPLC-QTOF-MS). Furthermore,with sodium danshensu as the internal reference substance,relative correction factors( RCFs) of protocatechuic aldehyde,caffeic acid,rosmarinic acid,lithospermic acid,and salvianolic acid B were calculated through slope analysis method,and the QAMS method was adopted to determine the contents of these 6 components. The UPLC fingerprint was employed to assess the consistency of 12 batches of Danshen Injection,which showed good batch-to-batch consistency with similarity higher than 0. 99. In the comparison of contents of the six constituents obtained by QAMS and external standard method( ESM),RSD was all less than 4. 3%,indicating the good accuracy of the QAMS method. The QAMS method developed in this study combined with UPLC fingerprint can comprehensively reflect the internal quality of Danshen Injection when only the reference substance sodium danshensu is consumed,with greatly reduced detection cost and time. It provides a technical basis for further improving the quality standard of Danshen Injection.

Effect of dual-acupoint and single-acupoint electric stimulation on postoperative outcomes in elderly patients subjected to gastrointestinal surgery: study protocol for a randomized controlled trial.

BACKGROUND: Transcutaneous electric acupoint stimulation (TEAS) has shown benefits when used peri-operatively. However, the role of numbers of areas with acupoint stimulation is still unclear. Therefore, we report the protocol of a randomized controlled trial of using TEAS in elderly patients subjected to gastrointestinal surgery, and comparing dual-acupoint and single-acupoint stimulation. METHODS/DESIGN: A multicenter, randomized, controlled, three-arm design, large-scale trial is currently undergoing in four hospitals in China. Three hundred and forty-five participants are randomly assigned to three groups in a 1:1:1 ratio, receiving dual-acupoint TEAS, single-acupoint TEAS, and no stimulation, respectively. The primary outcome is incidence of pulmonary complications at 30 days after surgery. The secondary outcomes include the incidence of pulmonary complications at 3 days after surgery; the all-cause mortality within 30 days and 1 year after surgery; admission to the intensive care unit (ICU) and length of ICU stay within 30 days after surgery; the length of postoperative hospital stay; and medical costs during hospitalization after surgery. DISCUSSION: The result of this trial (which will be available in September 2019) will confirm whether TEAS before and during anesthesia could alleviate the postoperative pulmonary complications after gastrointestinal surgery in elderly patients, and whether dual-acupoint stimulation is more effective than single-acupoint stimulation. TRIALS REGISTRATIONS: ClinicalTrials.gov, ID: NCT03230045 . Registered on 10 July 2017.

Comprehensive overview and assessment of computational prediction of microRNA targets in animals.

MicroRNAs (miRNAs) are short endogenous noncoding RNAs that bind to target mRNAs, usually resulting in degradation and translational repression. Identification of miRNA targets is crucial for deciphering functional roles of the numerous miRNAs that are rapidly generated by sequencing efforts. Computational prediction methods are widely used for high-throughput generation of putative miRNA targets. We review a comprehensive collection of 38 miRNA sequence-based computational target predictors in animals that were developed over the past decade. Our in-depth analysis considers all significant perspectives including the underlying predictive methodologies with focus on how they draw from the mechanistic basis of the miRNA-mRNA interaction. We also discuss ease of use, availability, impact of the considered predictors and the evaluation protocols that were used to assess them. We are the first to comparatively and comprehensively evaluate seven representative methods when predicting miRNA targets at the duplex and gene levels. The gene-level evaluation is based on three benchmark data sets that rely on different ways to annotate targets including biochemical assays, microarrays and pSILAC. We offer practical advice on selection of appropriate predictors according to certain properties of miRNA sequences, characteristics of a specific application and desired levels of predictive quality. We also discuss future work related to the design of new models, data quality, improved usability, need for standardized evaluation and ability to predict mRNA expression changes.

[Multi-objective optimization of extraction process for red ginseng based upon extraction efficiency and cost control].

It is the objective of this study to optimize the extraction process of red ginseng to minimize the unit cost of extracting effective ingredients. The relation between the target variables of total quantity of ginsenosides and first extraction time, first extraction solution amount, second extraction time, second extract solution amount were studied with Box-Behnken experimental design method. At the same we also considered the cost of extraction solution and energy usage. The objective function was set as unit cost of target (total quantity of ginsenosides or its purity) for the multi-objective optimization of extraction process. As a result, the optimal process parameters were found as first extraction time (108.7 min), first extraction solution amount folds (12), second extraction time (30 min), second extraction solution amount folds (8) to minimize the unit cost. It indicated that this approach could potentially be used to optimize industrial extraction process for manufacturing Chinese medicine.

Profiling of glucosinolates and flavonoids in Rorippa indica (Linn.) Hiern. (Cruciferae) by UHPLC-PDA-ESI/HRMS(n).

An UHPLC-PDA-ESI/HRMS(n) profiling method was used to identify the glucosinolates and flavonoids of Rorippa indica (Cruciferae), a wild vegetable and Chinese herb used to treat cough, diarrhea, and rheumatoid arthritis. Thirty-three glucosinolates, more than 40 flavonol glycosides, and 18 other phenolic and common organic compounds were identified. The glucosinolates and polyphenols were separated by UHPLC. High-resolution deprotonated molecules provided high accuracy mass values that were used to determine formulas and provide putative identification of the glucosinolates and flavonoids. The fragments from multistage mass spectrometry were used to elucidate the structures. The concentrations of the main components were based on UV peak areas and molar relative response factors with a single calibration standard. This study found this plant to be a rich source for glucosinolates, containing 24 new glucosinolates, including 14 glucosylated glucosinolates that were previously unidentified.

[Strategy and core technologies for the secondary development of Chinese patent medicine].

Secondary development of Chinese Patent Medicine (CPM) is an effective and innovation-driven way for the leaping development of Chinese medicine industry with less investment and faster return. Aim to improving the efficacy, safety and batch-to-batch consistency of CPMs, the theory and methodology for the secondary development of CPMs, mode for cultivating superior CPM, approaches to reforming the pharmaceutical technology and the corresponding core technologies were proposed in this paper, which is summarized as 'One objective, Three analyses, Five definitudes and Seven improvements'.