Objective To evaluate the guidance value of VKORC1 and CYP2C9 gene polymorphism on clinical application of warfarin in patients with non-valvular atrial fibrillation (NVAF). Methods A total of 290 cases of patients with NVAF were identified and their baseline data , initial dose of warfarin and base INR measurement results were recorded, then the follow-up was conducted. The initial administration of warfarin to INR standard time for the first time, total amount of warfarin and the average daily amount were recorded. All participants′ venous blood was extracted for VKORC1 and CYP2C9 gene polymorphism test. Results VKORC1 AG/GG genotype patients had longer INR standard time and higer amount of warfarin than patients with AA (103.38 ± 65.29)g vs. (53.26 ± 24.02)g, P < 0.05. Patients with type CYP2C9 gene mutation had shortest INR standard time(9.10 ± 2.01)d vs. (13.07 ± 4.28)d, P < 0.05. and lowest administration amount of warfarin (28.80 ± 17.35)g vs. (55.45 ± 23.67)g, P < 0.05. Conclusion There exist significant differences of first adminstration amount of warfarin in patients with NVAF to INR standards. Warfarin dose for VKORC1 AA genotype patients is lower than that for GG/AG type; there is short INR standard time and less adminstration amount of warfarin for CYP2C9 genotypes AC/CC patients.

Objective:To explore the effects of smoking on lung function and physical fitness of college students.Method:168 college students on September 30, 2020 were selected as the research subjects by convenient sampling. According to whether they had been smoking for more than 3 years in the past or (and) now, they were divided into smoking group (66 cases, 39.3%) and non-smoking group (102 cases, 60.7%). The general demographic data, body composition, health fitness and lung function of all the included subjects were collected, and the health status of the two groups were compared, the relationship between lung function and healthy physical fitness in the smoking group was analyzed, and the influencing factors of forced vital capacity (FVC), forced expiratory volume in the first second (FEV 1) and expiratory vital capacity (EVC) were also analyzed. Results:The peak expiratory flow rate (PEF) of male college students in smoking group was lower than that of non-smoking group [(9.37±1.72) vs (10.04±1.69) L/s] ( F=5.051, P=0.026). The standing time with eyes closed and one foot of smoking group was longer than that of non-smoking group [(87.2±49.1) vs (63.6±39.7) s] ( F=9.327, P=0.003). The number of sit ups per minute of female college students in smoking group was less than that in non-smoking group [(39.5±7.5) vs (49.2±12.5) times/min] ( F=5.189, P=0.029). The peak inspiratory flow rate (PIF), FVC, FEV 1, EVC and PEF in the smoking group were positively correlated with grip strength, back muscle strength, number of sit ups, push ups, standing high jump and standing long jump ( P<0.001); through the analysis of relevant data, the estimation formula of lung function and health fitness items was obtained. Conclusion:Smoking is harmful to college students′ lung function and physical fitness.

Objective:To explore the relationship between workplace procrastination and illegitimate tasks in-kindergarten teachersand the role of work disengagement and coworker support in their relationship.Methods:A to-tal of 245 kindergarten teachers were selected from 3 cities in Zhejiang Province.They were assessed with the Workplace Procrastination Scale(WPS),Bern Illegitimate Tasks Scale(BITS),Work Disengagement Scale(WDS),Colleague Support Scale(CSS).The models were tested by using Process macro for SPSS,and non-para-metric percentile bootstrap method was used to analyze the mediating effect and moderating effect.Results:There were significant differences in the total scores of workplace procrastination among kindergarten teachers in different marital status,age,teaching age,education level,teaching gradeand kindergarten level(Ps＜0.05).Work disengage-ment played a significant mediating role between workplace procrastination and illegitimate tasks(indirect effect=0.26,95％CI:0.16-0.37).Coworker support played a significant moderating role in the impact of illegitimate tasks on work disengagement(simple slope=0.72,0.39;P＜0.001).Conclusion:It suggests that workplace pro-crastination is related to illegitimate tasksin kindergarten teachers.Work disengagement plays a mediating role in their relationship,and coworker support plays a moderating role in the first half of this mediating role.

Pulmonary fibrosis(PF)is an irreversible lung disease that is characterized by excessive scar tissue with a poor median survival rate of 2-3 years.The inhibition of transforming growth factor-β receptor type-Ⅰ(TGF-β RI)by an appropriate drug may provide a promising strategy for the treatment of this disease.Polygonum cuspidatum(PC)is a well-known traditional Chinese herbal medicine which has an anti-PF effect.Accordingly,a combination of high resolution mass spectrometry with an in silico strategy was developed as a new method to search for potential chemical ingredients of PC that target the TGF-β RI.Based on this strategy,a total of 24 ingredients were identified.Then,absorption,distribution,meta-bolism,and excretion(ADME)-related properties were subsequently predicted to exclude compounds with potentially undesirable pharmacokinetics behaviour.Molecular docking studies on TGF-β RI were adopted to discover new PF inhibitors.Eventually,a compound that exists in PC known as resveratrol was proven to have excellent biological activity on TGF-β RI,with an ICso of 2.211 μM in vitro.Furthermore,the complex formed through molecular docking was tested via molecular dynamics simulations,which revealed that resveratrol had strong interactions with residues of TGF-β RI.This study revealed that resveratrol has significant potential as a treatment for PF due to its ability to target TGF-β RI.In addition,this research demonstrated the exploration of natural products with excellent biological activities toward specific targets via high resolution mass spectrometry in combination with in silico technology is a promising strategy for the discovery of novel drugs.

Objective To establish an evaluation index system that can be used for medical quality assessment in clini-cal departments.Methods Based on literature analysis and key informant interview,the Delphi method was used to analyze the-importance and operability of the evaluation index system of medical quality in clinical departments.Results A clinical depart-ment medical quality assessment and evaluation system was established,consisting of 3 primary indicators,14 secondary indica-tors,and 24 tertiary indicators.Conclusion By building a medical quality assessment and evaluation index system in clinical departments,a simple,standardized,and highly operational management model is established for medical institutions to carry out medical quality management.It is conducive to directing clinical departments to focus on medical quality management,improving their medical quality awareness and management level,and promoting the high-quality development of public hospitals.

The febrile respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the focus of global attention. Up to now, the infection has been continuing to spread all over the world and it is urgent to develop specific drugs for SARS-CoV-2. Finding effective and safe drugs which are already available in the market for treating coronavirus disease 2019 (COVID-19) is one of the main strategies to solve the problem in time. As quinoline alkaloids against malaria, chloroquine and hydroxychloroquine have been proved to have the anti-SARS-CoV-2 activity. Quinoline alkaloids are expected to be important drugs for the treatment of COVID-19. In this article, the research and application of chloroquine and hydroxychloroquine are reviewed from the aspects of pharmacokinetics, drug interaction, clinical research progress, treatment plan optimization and resolution of optical enantiomers. The possible problems are summarized in order to provide reference for further research and clinical application of quinoline alkaloids in the treatment of COVID-19.

Objective:To compare the cost-effectiveness of hospitalized Chinese patients undergoing nucleic acid screening strategies for hepatitis B and hepatitis C, immunological screening strategy, and no screening strategy under different willingness to pay (WTP). The results might aid to decision-making for the optimal strategy.Methods:In this study, nucleic acid screening, immunological screening and no screening were used as screening strategies, and China′s GDP in 2021 (80 976 yuan) was used as the threshold of WTP to construct a Markov model. After introducing parameters related to the diagnosis and treatment of hepatitis B and C in inpatients, a cohort population of 100 000 inpatients was simulated by TreeAge Pro 2021 software, the total cost, total health effects, incremental cost-effectiveness ratio and average cost-effectiveness ratio of different screening strategies were calculated, and cost-effectiveness analysis was conducted. Univariate and probabilistic sensitivity analysis were used to assess the impact of parameter uncertainty on the final results.Results:Compared with the non-screening strategy, the incremental total cost of the hepatitis B immunological screening strategy for cohort patients was 11 049 536 yuan, and the incremental cost-effectiveness ratio was 24 762 yuan/quality-adjusted life years (QALY), while the total incremental cost of nucleic acid screening was 19 208 059 yuan, and the incremental cost-effectiveness ratio was 29 873 yuan/QALY; the incremental cost-effectiveness ratio of nucleic acid screening and immunological screening was 45 834 yuan/QALY. Compared with the non-screening strategy, the incremental cost-effectiveness ratio of hepatitis C immunological screening strategy was 5 731 yuan/QALY, the incremental cost-effectiveness ratio of nucleic acid screening strategy was 8 722 yuan/QALY, the incremental cost-effectiveness ratio of nucleic acid screening and immunological screening was 45 591 yuan/QALY. The results of probabilistic sensitivity analysis showed that when the cost of nucleic acid testing exceeded 214.53 yuan, it was not cost-effective to perform hepatitis B nucleic acid screening under the WTP as 1 fold GDP. When the cost of nucleic acid testing exceeded 132.18 yuan, it was not cost-effective to conduct hepatitis C screening under the WTP as 1 fold GDP.Conclusions:Nucleic acid screening strategy can achieve more cost-effectiveness and is worthy of vigorous promotion. Compared with no screening, both the nucleic acid and immunological screening strategies are cost-effective, and hepatitis nucleic acid screening is the optimal strategy for hospitalized patients.

Obstructive sleep apnea （OSA） is a sleep disorder with a slow course and is often accompanied by multiple serious complications， having highly consistent pathogenic characteristics with the latent pathogen. By exploreing its pathogenesis and treatment based on the latent pathogen theory in traditional Chinese medicine， it is believed that congenital healthy qi deficiency is the root， while internal latent phlegm and stasis is the branch， and external pathogenic seven emotions are causing factors. In terms of treatment， it is necessary to target at root deficiency and use nourishing medicinals according to depletion degree of lungs， spleen， and kidneys. When protecting the healthy qi， it is important to prevent the generation and inducing of latent pathogen. Simultaneously， it is also critical to put focus on phlegm stasis by clearing existing latent pathogens with medicinals having the function of dissolving phlegm and dispelling stasis， as well as regulating liver and lung qi. All these are expected to provide new ideas and methods for the treatment of OSA patients in clinical practice.

OBJECTIVE: To determine whether miRNA-128-3p regulates malignant biological behavior of glioma cells by targeting KLHDC8A. METHODS: Dual-luciferase reporter assays, qRT-PCR and Western blotting were used to verify the targeting of miRNA-128-3p to KLHDC8A. Edu assay, flow cytometry, Transwell assay and would healing assay were used to determine the effects of changes in miRNA-128-3p and KLHDC8A expression levels on malignant behavior of glioma cells. Rescue experiment was carried out to verify that miRNA-128-3p regulated glioma cell proliferation, apoptosis, invasion and migration by targeting KLHDC8A. RESULTS: The expression level of KLHDC8A was significantly increased in high-grade glioma tissue and was closely related to a poor survival outcome of the patients. Overexpression of KLHDC8A promoted glioma cell proliferation, migration and invasion, and miRNA-128-3p overexpression inhibited proliferative and metastatic capacities of glioma cells. Mechanistically, KLHDC8A expression was directly modulated by miRNA-128-3p, which, by targeting KLHDC8A, inhibited malignant behavior of glioma cells. CONCLUSION Upregulation of miRNA-128-3p inhibits uncontrolled growth of glioma cells by negatively regulating KLHDC8A expression and its downstream effectors, suggesting that the miRNA-128-3p-KLHDC8A axis may serve as a potential prognostic indicator and a therapeutic target for developing new strategies for glioma treatment.
Humans ; Apoptosis ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glioma/pathology* ; MicroRNAs/metabolism* ; Up-Regulation

Heme, which exists widely in living organisms, is a porphyrin compound with a variety of physiological functions. Bacillus amyloliquefaciens is an important industrial strain with the characteristics of easy cultivation and strong ability for expression and secretion of proteins. In order to screen the optimal starting strain for heme synthesis, the laboratory preserved strains were screened with and without addition of 5-aminolevulinic acid (ALA). There was no significant difference in the heme production of strains BA, BAΔ6 and BAΔ6ΔsigF. However, upon addition of ALA, the heme titer and specific heme production of strain BAΔ6ΔsigF were the highest, reaching 200.77 μmol/L and 615.70 μmol/(L·g DCW), respectively. Subsequently, the hemX gene (encoding the cytochrome assembly protein HemX) of strain BAΔ6ΔsigF was knocked out to explore its role in heme synthesis. It was found that the fermentation broth of the knockout strain turned red, while the growth was not significantly affected. The highest ALA concentration in flask fermentation reached 82.13 mg/L at 12 h, which was slightly higher than that of the control 75.11 mg/L. When ALA was not added, the heme titer and specific heme production were 1.99 times and 1.45 times that of the control, respectively. After adding ALA, the heme titer and specific heme production were 2.08 times and 1.72 times higher than that of the control, respectively. Real-time quantitative fluorescent PCR showed that the expressions of hemA, hemL, hemB, hemC, hemD, and hemQ genes at transcription level were up-regulated. We demonstrated that deletion of hemX gene can improve the production of heme, which may facilitate future development of heme-producing strain.
Gene Deletion ; Bacillus amyloliquefaciens/metabolism* ; Aminolevulinic Acid/metabolism* ; Heme/metabolism* ; Fermentation