Objective To observe the effects of acute normovolemic hemodilution(ANH)on target-controlled infusion(TCI)of etomidate blood drug concentration and adrenal cortical function.Methods Sixty patients who undergo elective multisegmental spine surgery,35 males and 25 females,aged 30-60 years,BMI 20-25 kg/m2,ASA physical status Ⅰ or Ⅱ,were divided into two groups using random number table method:ANH group and control group,30 patients in each group.Both groups used a target-controlled infusion of etomidate for anesthesia induction and anesthesia maintenance.In the ANH group,ANH was performed after steady anesthesia induction,ideal Hct 28％to 30％,and transfused within 1 hour after surgery;the control group was routinely treated.The dosage of etomidate was recorded.Liquid chroma-tography-tandem mass spectrometry(LC-MS/MS)was used to detect etomidate blood concentrations at the immediate postoperative,10,20,and 30 minutes postoperative periods in the two groups,and the immedi-ate moment autologous blood collected into the storage bag,preserved in the storage bag for 1 hour,and the immediate moment transfused back in the ANH group.Plasma concentrations of cortisol(Cor),adrenocorti-cotropic hormone(ACTH),and aldosterone(ALD)were measured by chemiluminescence immunoassay(CLIA)before the induction of anesthesia,immediately after the operation,and at 1 day and 2 days postop-eratively.Results There was no significant difference in the total dosage of etomidate between the two groups.Compared with the immediate postoperative period,the plasma etomidate concentration was signifi-cantly decreased 10,20,and 30 minutes after surgery(P<0.05).Compared with the control group,the concentration increased significantly 10 minutes after surgery in the ANH group(P<0.05).The plasma concentrations of etomidate were(547.8±119.4)ng/ml at the immediate moment autologous blood collected into the storage bag,(536.7±107.8)ng/ml at the preserved in the storage bag for 1 hour,and(522.8±91.7)ng/ml at theimmediatemoment transfusedbackinthe ANHgroup.Comparedwithbeforein-duction of anesthesia,the concentration of Cor and ALD immediately after the operation decreased signifi-cantly(P<0.05)and the concentration of ACTH was significantly higher(P<0.05).There were no sta-tistically significant differences in the concentrations of Cor,ALD,and ACTH between the two groups before induction of anesthesia 1 day and 2 days postoperatively.Conclusion In the orthopedic surgery of TCI eto-midate,return transfusion of collected autologous blood transiently(about 10 minutes)increases etomidate blood concentrations,the function of adrenal cortical will recover to the preoperative level within 24 hours after the operation.

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

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.

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

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

Pharmacists are important members of the multidisciplinary team of anti-tumor therapy. With the transformation of pharmacists, the content of pharmaceutical care provided by oncology pharmacists continues to extend. Expanded services such as clinical comprehensive evaluation of anti-tumor drugs and management of off-label drug use are an important development trend of oncology pharmacy. The column named “Oncology Pharmacy Management and Services” is introduced, which discussed in depth from the two parts of “frontier progress of anti-tumor drugs” and “comprehensive clinical evaluation of anti-tumor drugs”, aiming to provide new ideas for the exploration of oncology pharmaceutical services, so as to further accelerate the transformation of oncology pharmaceutical care and promote the high-quality development of oncology pharmacy.

Objective:To establish a risk prediction model for hospital acute heart failure in elderly patients with chronic heart failure (CHF) .Methods:From January 2018 to December 2020, 619 elderly CHF patients admitted to the Cardiovascular Department of Peking University Third Hospital were selected as the research object by convenience sampling. The patients were divided into the occurrence group ( n=55) and the non-occurrence group ( n=564) according to whether the patients had acute heart failure in hospital. Binomial Logistic regression was used to explore the independent risk factors of acute heart failure in elderly CHF patients. The nomogram model was constructed by R software, and its prediction effect was verified. Results:Binomial Logistic regression showed that high heart rate at admission [ OR=1.021, 95% CI (1.003, 1.039) ], history of cerebrovascular disease [ OR=2.253, 95% CI (1.197, 4.240) ], constipation [ OR=10.382, 95% CI (1.376, 78.308) ], arrhythmia [ OR=2.051, 95% CI (1.079, 3.898) , taking aspirin [ OR=2.741, 95% CI (1.447, 5.193) ], intravenous diuretics [ OR=6.326, 95% CI (2.629, 15.220) ]and high level of N-terminal forebrain natriuretic peptide [ OR=3.511, 95% CI (1.890, 6.521) ]were independent risk factors for hospital onset of acute heart failure in elderly patients with CHF, and the use of vasodilator was a protective factor. The nomogram model was validated. The area under the receiver operating characteristic curve ( AUC) of the subject was 0.808 [95% CI (0.753, 0.864) ], the AUC of internal validation was 0.821 [95% CI (0.764, 0.871) ], and the calibration curve was a straight line with a slope close to 1. Conclusions:There are many risk factors of hospital acute heart failure in elderly CHF patients. The prediction model based on risk factors has good discrimination and calibration, and can predict the risk of acute heart failure in elderly CHF patients in hospital.

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.

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.

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.