Alteration of metabolism and epigenetic status are two new focuses in the field of cancer re -search.Recently,more and more reports have demonstrated that the changes of both metabolic enzymes and al -tered epigenetic status have close interrelationship with the pathogenesis and development of gliomas in human . We discuss here the effects of altered metabolic enzymes on epigenetic status in gliomas based on two important altered metabolic enzymes ,with the aim to unlock the molecular mechanism on how gliomas occur and progress . This newfound molecular mechanism of how altered metabolic enzymes impact on epigenetic status in gliomas may contribute to the identification of novel therapeutic targets to gliomas in the future .

OBJECTIVE:To provide reference for rational use of leucocyte increasing drugs in patients with lung cancer. METHODS:The application of drugs in lung cancer patients in 40 d each year were collected from 11 Zhejiang hospitals during 2009-2014,and then analyzed retrospectively in consumption sum,DDDs,DDC and department distribution,etc. RESULTS:The proportion of consumption sum of leucocyte increasing drugs in total consumption sum decreased generally in 11 Zhejiang hospital during 2009-2014,decreasing from 781 995.50 yuan in 2009(3.28%)to 626 792.80 yuan in 2014(1.53%). Top 3 departments in the list of consumption sum of leucocyte increasing drugs were oncology department(29.00%),radiotherapy department(27.08%) and respiratory medicine department(9.93%). Top 3 drugs in the list of consumption sum during 2009-2014 were recombinant hu-man granulocyte colony-stimulating factor,Coenzyme complex for injection and Leucogen tablets;top 3 drugs in the list of DDDs were Leucogen tablets,Berbamine tablet and recombinant human granulocyte colony-stimulating factor;Coenzyme complex for in-jection,recombinant human granulocyte colony-stimulating factor and human GM-CSF took the first three place in the list of DDC during 2009-2013,and Leucogen tablets were the top one in 2014. CONCLUSIONS:The application of leucocyte increasing drugs in lung cancer patients is decreasing year by year in 11 Zhejiang hospitals,and those with definite therapeutic efficacy and moder-ate price predominate clinical application predominate in the clinical practive.

Objective To explore the effect of pain management by pain resource nurse (PRN) attending pain nursing group, and to know the patient′s satisfaction. Methods Advanced practice nurse as the lead of the group. The selection of PRN members in the group was made on merit which all have definite responsibility and like pain nursing, established pain management quality control system in group and training,standardized pain management processes and the regulations, educated knowledge and skills of pain management for PRN. Results Patient satisfaction with pain management increased significantly from 82.0%(496/605) to 97.1%(572/589)(P<0.05). Moderate and serious pain rate of patients decreased significantly from 60.0%to 20.0%(P<0.01). The qualified rate of pain assessment increased from 84.9%(514/605) to 95.1%(560/589)(P<0.05). Conclusions The establishment of pain nursing group can not only improve pain management quality and patients satisfaction, but also improve of PRN′s professional behaviors and development of clinical pain nursing .

Objective: To investigate the utilization status of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in 11 hospitals of Zhejiang province from 2009 to 2015, and to analyze the use rationality.Methods: The doctor's advice in 40 days annually was collected in 11 hospitals of Zhejiang province from 2009 to 2015, and the drug consumption, frequency of utilization (DDDs), defined daily cost (DDC) and drug utilization index (DUI) were analyzed for the patients with lung cancer treated with EGFR-TKI.Results: Icotinib, erlotinib and gefitinib were the three prevalent EGFR-TKIs used in Zhejiang province, and icotinib started to be used in clinics in 2013.The overall cost of EGFR-TKIs increased year by year during 2009 and 2015, and the total amount of sales increased by 4.67 times in 2015 when compared with that in 2009.Generally, the DDDs value of erlotinib showed a decreasing trend, however, that of icotinib and gefitinib rose year by year during 2009 and 2015.Erlotinib had the highest DDC followed by gefitinib and icotinib.The mean value of DUI of the three targeted drugs was about 1.Conclusion: The utilization of EGFR-TKI is reasonable in 11 hospitals of Zhejiang province with increasing comsuption.

Objective Based on the traditional Chinese medical knowledge service and sharing system, to explore the application of famous doctor Yu Ying'ao's regulating the liver method. Methods The medical records of Yu Ying'ao from the outpatient department of Chinese Academy of Sciences were used as the data source. The traditional Chinese medical knowledge service and information sharing system(V1.1.5) was applied to construct database. The regulating liver core combination of drugs, drug application mode, and combined treatment of diseases and syndromes were determined by analysis methods of frequency and association rules. Results The use of regulating liver method was often used in the treatment of irregular menstruation, cirrhosis, pain and other diseases. Differentiation of liver qi stagnation, blood stasis, liver stagnation and spleen deficiency, liver and kidney deficiency were the main TCM syndromes. Treatment included Tongluo, nourishing Yin treatment. The core drugs were Bupleurum and Rhizoma Cyperi. Conclusions The use of traditional Chinese medical service and knowledge sharing system could explore the clinical diagnosis and medication rules of regulating liver methods.

Outpatient information management system is an important part of hospital information system,which plays an important role in hospital management,patient treatment,medical insurance reimbursement and settlement.This study integrated the application modes of big data,cloud computing,Internet of things and other cutting-edge technologies of artificial intelligence,focused on the intelligent decision support and whole-process simplified management of the diagnosis and treatment behavior of clinical TCM physicians,and developed a cloud intelligent TCM outpatient system for primary medical care.The system has intelligent medical functions such as intelligent prescription monitoring driven by the rule engine and intelligent recommendation of traditional Chinese medicine knowledge.It seamlessly connects with the intelligent four-diagnosis instrument for information collection and medical order input,and realizes the cloud storage,computing,distribution,management,service and outpatient process,multi-directional and convenient management mode.

The international TCM clinical knowledge database is demand-oriented, fully integrated TM resources of the Institute of Information on Traditional Chinese Medicine of China Academy of Chinese Medical Sciences that has accumulated for decades, with increased new resources. The resources are structured by subject indexing, classification and knowledge extraction, and are hierarchically translated by machine translation and manned proofreading. In addition, the research group also designs and develops service platform using ontology, semantic web, association relationship and other information technology. The knowledge database will provide knowledge service to TCM practitioners and the general public worldwide, and promote the internationalization of TCM.

CRISPR-Associated Protein 9 ; Gene Editing ; CRISPR-Cas Systems/genetics*

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans ; Apolipoprotein E4/genetics* ; Cytosine ; Mutation ; Blastocyst ; Heterozygote ; Gene Editing ; CRISPR-Cas Systems

BACKGROUND: This study aimed to develop a comprehensive instrument for evaluating and ranking clinical practice guidelines, named Scientific, Transparent and Applicable Rankings tool (STAR), and test its reliability, validity, and usability. METHODS: This study set up a multidisciplinary working group including guideline methodologists, statisticians, journal editors, clinicians, and other experts. Scoping review, Delphi methods, and hierarchical analysis were used to develop the STAR tool. We evaluated the instrument's intrinsic and interrater reliability, content and criterion validity, and usability. RESULTS: STAR contained 39 items grouped into 11 domains. The mean intrinsic reliability of the domains, indicated by Cronbach's α coefficient, was 0.588 (95% confidence interval [CI]: 0.414, 0.762). Interrater reliability as assessed with Cohen's kappa coefficient was 0.774 (95% CI: 0.740, 0.807) for methodological evaluators and 0.618 (95% CI: 0.587, 0.648) for clinical evaluators. The overall content validity index was 0.905. Pearson's r correlation for criterion validity was 0.885 (95% CI: 0.804, 0.932). The mean usability score of the items was 4.6 and the median time spent to evaluate each guideline was 20 min. CONCLUSION The instrument performed well in terms of reliability, validity, and efficiency, and can be used for comprehensively evaluating and ranking guidelines.
Reproducibility of Results ; Surveys and Questionnaires ; Practice Guidelines as Topic ; Humans