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This study used m-chloropheniperazine(MCPP) and chronic unforeseeable mild stress(CUMS) to induce the rat models of anxiety and depression, respectively. The behaviors of rats were observed by the open field test(OFT), light-dark exploration test(LDE), tail suspension test(TST), and forced swimming test(FST), and the antidepressant and anxiolytic effects of agarwood essential oil(AEO), agarwood fragrant powder(AFP), and agarwood line incense(ALI) were explored. The enzyme-linked immunosorbent assay(ELISA) was used to determine the levels of 5-hydroxytryptamine(5-HT), glutamic acid(Glu), and γ-aminobutyric acid(GABA_A) in the hippocampal area. The Western blot assay was used to determine the protein expression levels of glutamate receptor 1(GluR1) and vesicular glutamate transporter type 1(VGluT1), exploring the anxiolytic and antidepressant mechanism of agarwood inhalation. The results showed that compared with the anxiety model group, the AEO, AFP, and ALI groups decreased the total distance(P<0.05), decreased the velocity of movements(P<0.05), prolonged the immobile time(P<0.05), and reduced the distance and velocity of the rat model of anxiety in the dark box(P<0.05). Compared with the depression model group, the AEO, AFP, and ALI groups increased the total distance and average velocity(P<0.05), reduced the immobile time(P<0.05), and reduced the forced swimming and tail suspension time(P<0.05). In terms of transmitter regulation, the AEO, AFP, and ALI groups decreased the level of Glu in the rat model of anxiety(P<0.05) and increased the levels of GABA_A and 5-HT(P<0.05), while the AEO, AFP, and ALI groups all increased the level of 5-HT in the rat model of depression(P<0.05) and decreased the levels of GABA_A and Glu(P<0.05). At the same time, the AEO, AFP, and ALI groups all increased the protein expression levels of GluR1 and VGluT1 in the hippocampus of the rat models of anxiety and depression(P<0.05). In conclusion, AEO, AFP, and ALI exert anxiolytic and antidepressant effects, and the mechanism might be related to the regulation of the neurotransmitter and the protein expression of GluR1 and VGluT1 in the hippocampus.
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Animals , Rats , Anti-Anxiety Agents , Serotonin , alpha-Fetoproteins , Antidepressive Agents , Glutamic Acid , gamma-Aminobutyric AcidABSTRACT
Objective To rapidly identify and assign the chemical components in Sugemule-4 decoction by using UPLC Orbitrap Exploris MS/MS,and then conduct network pharmacological analysis,and clarify the anti-insomnia effect of Sugmule-4 decoction.Methods ACQUITY UPLC BEH C18(2.1 mm×100 mm,1.7 μm)Chromatographic column,with 0.1%formic acid aqueous solution(A)-0.1%formic acid acetonitrile solution(B)as mobile phase gradient elution.Flow rate:0.5 mL·min-1,injection volume:5 μL.Under the control of the control software(Xcalibur,Thermo Fisher Scientific),the primary and secondary mass spectrometry data are collected based on the FullScan-ddMS2 function.Combined with the self-built database and online database,the chemical components in Sugemule-4 decoction are identified by accurate relative molecular weight,fragment ion information,pyrolysis pattern and comparison of control samples.The identified chemical components were analyzed by network pharmacology,and the targets of drug and insomnia were obtained from TCMSP,SwissTargetPrediction,GeneCards,OMIM,TTD,DrugBank and DisGeNET databases respectively,and the intersection target was obtained;Protein interaction analysis was performed through STRING database.Use Metascape platform to analyze GO function and KEGG pathway,and predict the mechanism of Sugmule-4 decoction in treating insomnia.To determine the anti-insomnia effect of Sugmule-4 decoction,SD rats were divided into normal control group(K),model group(M),Sugmule-4 decoction group(S)and Anshenbunao liquid group(A).After chronic unpredictable mild stress and PCPA were used for modeling,the rats were given corresponding drugs by gavage for 7 days,then the open field text was conducted to observe the general state and behavioral changes,and detection of AChE,5-HT,and GABA levels in serum and brain tissue of rats in each group using ELISA method.Results 136 components were identified from Sugemule-4 decoction,including 37 terpenoids,34 alkaloids,26 flavonoids,20 phenylpropanoids,14 phenolic acids and 5 amino acids.The results of network pharmacology analysis show that the mechanism of Sugemule-4 decoction in treating insomnia is mainly achieved by its components such as Romucosine D,Nornantenine,Nuciferine,and(R)-ar Turbone acting on targets such as ACHE,ADORA2A,and CHRM1 through signal pathways such as Neuroactive ligand-receptor interaction,synaptic signaling,and trans synaptic signaling.This is a multi component-multi target-multi signal pathway joint implementation process.The results of pharmacodynamic experiment showed that Sugmule-4 decoction and Anshenbunao liquid could revise the general state and behavioral changes of insomnia model rats,increase the content of AChE,5-HT and GABA in serum(P<0.01).Conclusion This study comprehensively reflects the chemical components of Sugmule-4 decoction,and preliminarily summarizes the mass spectrum decomposition characteristics of various chemical components.The network pharmacology and pharmacodynamics experiments show that Sugmule-4 decoction has significant anti-insomnia effect,which provides a reference basis for the quality control and mechanism study of Sugmule-4 decoction.
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AIM To isolate and identify the dominant strains in the fermentation process of the HuaFengDan YaoMu,and to investigate the effects of different temperatures and pH values upon their growth.METHODS During the 0-6 weeks fermentation process of HuaFengDan YaoMu in the selective medium,the cultured bacteria,the molds and the yeasts had the colonies counted,and the dominant strains isolated and purified,particularly the dominant bacteria and fungi determined by 16S rDNA and 26S rDNA sequences.The optimal growth temperature and pH value of Bacillus aryabhattai,Debaryomyces hansenii,Aspergillus oryzae were investigated respectively.RESULTS HuaFengDan YaoMu found its bacterial counts increased from 0 to 4 weeks and stabilized from 4 to 6 weeks;its yeast counts increased during 0-3 weeks,and decreased continuously during 4-6 weeks;and its mold counts remained unchanged at 0 week,but increased steadily from 1 to 4 weeks,and decreased at 5 to 6 weeks of the fermentation.In the fermentation process of HuaFengDan YaoMu,the dominant strains of Bacillus aryabhattai,Debaryomyces hansenii and Aspergillus oryzae,identified and screened out by the phylogenetic tree,adapted best to the growth temperature of 35℃,25-30℃and 35℃,at pH value of 8,6 and 7,respectively.CONCLUSION In the fermentation process of HuaFengDan YaoMu,the dominant microorganisms of Bacillus aryabhattai,Debaryomyces hansenii,Aspergillus oryzae are identifiable and separable.
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Objective:To construct an evaluation index system for the reform of public hospital salary system and conduct empirical research, for reference in deepening the reform of public hospital salary system.Methods:Based on the building blocks of health systems and the Guiding Opinions on Pilot Work of Public Hospital Salary System Reform (Human Resources and Social Security Ministry 〔2017〕 No. 10), a preliminary index system was constructed. And the expert consultation method was used to determine the evaluation index system for public hospital salary system reform. The authors selected representative hospitals in Chaoyang district of Beijing with reform experiences of such salary system, and applied this index system for empirical research. Objective indexes were extracted from the hospital information system, which were used to evaluate relevant data before the reform (from 2016 to 2017) and after the reform (from 2018 to 2019); a questionnaire was customized based on the subjective indexes in the index system, which was used for a questionnaire survey on hospital staff, outpatient patients, and inpatients. A descriptive analysis was made on such indexes as hospital revenue and expenditure, medical expenses, salary levels, and satisfaction. The comparison of relevant data before and after the reform was conducted using one-way ANOVA. Results:This study constructed a public hospital salary system reform evaluation system, comprising 4 first-level indexes, 8 second-level indexes, and 38 third-level indexes. second-level indexes were salary level and structure, salary governance and information construction, health manpower and service provision, medical products and technology. There were 28 objective indexes and 10 subjective ones. The evaluation results of 4 representative public hospitals showed that the proportion of labor costs, hygiene materials income, treatment income, nursing income, and physician service fees to the total income increased as compared to that before the reform, with statistical significance ( P<0.05); The average medical expenses of discharged patients and the proportion of drug income (excluding traditional Chinese medicine slices) to total income decreased compared to that before the reform, and the difference was statistically significant ( P<0.05); The difference between the average medical expenses per outpatient visit and the proportion of surgical income to total income was not statistically significant ( P>0.05). There was no statistically significant difference in salary levels among employees of different genders, seniority, and educational backgrounds ( P>0.05). On the other hand, there was a statistically significant difference in salary levels among employees of different ages, majors, professional and technical titles, and employment types ( P<0.05). The actual salary of 636 employee was only 56.26% of the expected salary, and their total score of salary satisfaction was (3.33 ± 0.86) points. The scores of public service motivation, medical service quality, and job satisfaction were (3.52 ± 0.78) points, (3.91 ± 0.77) points, and (3.72 ± 0.65) points, respectively. The satisfaction scores of outpatient and inpatient patients were (4.64 ± 0.23) and (4.82 ± 0.45), respectively. Conclusions:The evaluation system for the reform of the salary system in public hospitals constructed in this study can comprehensively evaluate the effectiveness of hospital reform from a multidimensional perspective, combining quantitative and qualitative, subjective and objective aspects. It proves scientific and practical.
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Alcoholic liver disease (ALD) is a growing global health concern, and its early pathogenesis includes steatosis and steatohepatitis. Inhibiting lipid accumulation and inflammation is a crucial step in relieving ALD. Evidence shows that puerarin (Pue), an isoflavone isolated from Pueraria lobata, exerts cardio-protective, neuroprotective, anti-inflammatory, antioxidant activities. However, the therapeutic potential of Pue on ALD remains unknown. In the study, both the NIAAA model and ethanol (EtOH)-induced AML-12 cell were used to explore the protective effect of Pue on alcoholic liver injury in vivo and in vitro and related mechanism. The results showed that Pue (100 mg·kg-1) attenuated EtOH-induced liver injury and inhibited the levels of SREBP-1c, TNF-α, IL-6 and IL-1β, compared with silymarin (Sil, 100 mg·kg-1). In vitro results were consistent within vivo results. Mechanistically, Pue might suppress liver lipid accumulation and inflammation by regulating MMP8. In conclusion, Pue might be a promising clinical candidate for ALD treatment.
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ObjectiveTo explore the association between daily executive function and core symptoms, the symptoms of attention deficit hyperactivity disorder (ADHD) in children with autism spectrum disorder (ASD), and the moderating effect of theory of mind and other cognitive abilities on this association. MethodsChildren aged 6-12 years with ASD were recruited, and 86 children were identified according to the inclusion and exclusion criteria. Wechsler Intelligence Test for Children, Fourth Edition (WISC-Ⅳ), Strange Story Test (SST) and Behavior Rating Inventory of Executive Function (BRIEF) were used to evaluate children's cognitive ability. Swanson Nolan and Pelham-Version Ⅳ Scale (SNAP-Ⅳ), Social Responsiveness Scale (SRS), and Repetitive Behavior Scale-Revise (RBS-R) were used to assess the severity of ADHD symptoms, social impairment, and repetitive stereotyped behavior. Multiple linear regression was used to explore the association between daily executive function and ADHD symptoms, social impairment, repetitive stereotyped behaviors. ResultsAfter controlling for the score of strange stories, verbal comprehension index (VCI) and other factors, the full scale score and each index of BRIEF were positively correlated with full scale score of SNAP (b = 0.619-0.741, b’ = 0.637-0.755), SRS (b = 0.928-1.200, b’ = 0.417-0.513) and RBS-R (b = 0.326-0.525, b’ = 0.339-0.520) in children with ASD (P< 0.05), and the SNAP total score was more strongly correlated with the full scale BRIEF score and each index score (b’ = 0.637-0.755,P< 0.01). In addition to daily executive function, strange stories score (b = -2.218- -1.839) and age (b = 3.181-4.037) were also the important factors affecting the social function of children with ASD (P< 0.01). There were no moderating effects of strange stories score and age on the association between BRIEF score and full scale score of SNAP, SRS, and RBS-R(P> 0.05). ConclusionThe deficits of daily executive function in school-aged ASD children are significantly associated with core symptoms and ADHD symptoms, and the association is independent of other cognitive domains, such as theory of mind and verbal comprehension intelligence quotient.
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Objective:To analyze the electrophysiological characteristics and influencing factors of peripheral neuropathy in Parkinson's disease(PD)patients.Methods:Totally 68 PD patients and 30 controls were selected for neuroelectrophysiological evaluation, including items such as limb motor nerve terminal latency(LP)and amplitude and sensory nerve conduction velocity(SCV)and amplitude.Age, sex, serum folate, vitamin B 12, homocysteine and hemoglobin levels were also recorded for the two groups.The Hoehn-Yahr scale was used to assess patients and levodopa daily doses and levodopa equivalent daily doses were calculated.According to the criteria for neuroelectrophysiological abnormalities, 31 PD patients were found to have peripheral neuropathy and 37 PD patients did not have peripheral neuropathy. Results:In PD patients, a total of 952 peripheral nerves were examined, with 21.7% having motor nerve involvement(118/544)and 72.8%(297/of 408)having sensory nerve involvement.In the control group, a total of 420 peripheral nerves were examined, with 4.2%(10/240)having motor nerve involvement and 26.1%(47/180)having sensory nerve involvement.Compared with the control group, the wave amplitudes of motor nerve terminals were reduced in the PD group for the ulnar nerve( t=2.172/2.345, right/left), median nerve( t=2.104/2.543, right/left), and tibial nerve( t=2.340/2.444, right/left)(all P<0.05); compared with the control group, the wave amplitudes of sensory nerve terminals of the ulnar nerve( Z=3.535/3.439, right/ left), median nerve( Z=3.076/2.937, right/left), and peroneal nerve( Z=2.795/2.795, right/left)were all reduced in the PD group(all P<0.05); compared with the control group, sensory conduction velocities of the ulnar nerve( t=2.326/2.487, right/left), median nerve( t=3.269/2.386, right/left), and peroneal nerve( t=2.551/2.418, right/left)were prolonged(all P<0.05). The rate of abnormalities with the sensory nerve terminal wave amplitude( χ2=149.814, P<0.001)was higher than that of abnormalities with motor nerve terminal wave amplitude in PD patients; the rate of abnormalities with the sensory nerve terminal wave amplitude( χ2=58.364, P<0.001)was higher than that of abnormalities with sensory conduction velocities.Logistic regression analysis showed that increased folic acid( OR=0.825, 95% CI: 0.637-0.990)and vitamin B 12( OR=0.996, 95% CI: 0.991-1.000)were protective factors for PD peripheral neuropathy; H-Y score, levodopa daily dose( OR=1.009, 95% CI: 1.003-1.015), and increased homocysteine( OR=1.151, 95% CI: 1.041-1.273)were risk factors for PD peripheral neuropathy.After excluding confounding factors, H-Y classification( OR=3.213, 95% CI: 1.342-7.713)remained an independent risk factor for peripheral nerve injury in PD patients. Conclusions:In PD patients with peripheral neuropathy, both motor nerves and sensory nerves are involved, sensory nerves are more significantly involved, and axonal damage is more important than myelin loss; increased H-Y classification is an independent risk factor for peripheral nerve injury in PD patients.
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Artemisia argyi is an important medicinal and economic plant in China, with the effects of warming channels, dispersing cold, and relieving pain, inflammation, and allergy. The essential oil of this plant is rich in volatile terpenoids and widely used in moxi-bustion and healthcare products, with huge market potential. The bZIP transcription factors compose a large family in plants and are involved in the regulation of plant growth and development, stress response, and biosynthesis of secondary metabolites such as terpenoids. However, little is known about the bZIPs and their roles in A. argyi. In this study, the bZIP transcription factors in the genome of A. argyi were systematically identified, and their physicochemical properties, phylogenetic relationship, conserved motifs, and promoter-binding elements were analyzed. Candidate AarbZIP genes involved in terpenoid biosynthesis were screened out. The results showed that a total of 156 AarbZIP transcription factors were identified at the genomic level, with the lengths of 99-618 aa, the molecular weights of 11.7-67.8 kDa, and the theoretical isoelectric points of 4.56-10.16. According to the classification of bZIPs in Arabidopsis thaliana, the 156 AarbZIPs were classified into 12 subfamilies, and the members in the same subfamily had similar conserved motifs. The cis-acting elements of promoters showed that AarbZIP genes were possibly involved in light and hormonal pathways. Five AarbZIP genes that may be involved in the regulation of terpenoid biosynthesis were screened out by homologous alignment and phylogenetic analysis. The qRT-PCR results showed that the expression levels of the five AarbZIP genes varied significantly in different tissues of A. argyi. Specifically, AarbZIP29 and AarbZIP55 were highly expressed in the leaves and AarbZIP81, AarbZIP130, and AarbZIP150 in the flower buds. This study lays a foundation for the functional study of bZIP genes and their regulatory roles in the terpenoid biosynthesis in A. argyi.
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Gene Expression Profiling , Phylogeny , Artemisia/genetics , Basic-Leucine Zipper Transcription Factors/metabolism , Terpenes , Gene Expression Regulation, PlantABSTRACT
Andrographis Herba, the aerial part of Andrographis paniculata (Burm. f.) Wall. ex Nees (Acanthaceae), has a wide geographic distribution and has been used for the treatment of fever, cold, inflammation, and other infectious diseases. In markets, sellers and buyers commonly inadvertently confuse with related species. In addition, most Chinese medicinal herbs are subjected to traditional processing procedures, such as steaming and boiling, before they are sold at dispensaries; therefore, it is very difficult to identify Andrographis Herba when it is processed into Chinese medicines. The identification of species and processed medicinal materials is a growing issue in the marketplace. However, conventional methods of identification have limitations, while DNA barcoding has received considerable attention as a new potential means to identify species and processed medicinal materials. In this study, 17 standard reference materials of A. paniculata, 2 standard decoctions, 27 commercial products and two adulterants were collected. Based on the ITS2 sequence, it could successfully identify A. paniculata and adulterants. Moreover, a nucleotide signature consisting of 71 bp was designed, this sequence is highly conserved and specific within A. paniculata while divergent among other species. Then, we used these new primers to amplify the nucleotide signature region from processed materials. In conclusion, the DNA barcoding method developed in the present study for authenticating A. paniculata is rapid and cost-effective. It can be used in the future to guarantee the quality of Andrographis Herba of each regulatory link for clinical use.
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Andrographis , Andrographis paniculata , DNA Primers , Drugs, Chinese HerbalABSTRACT
Artemisia Argyi Folium, a traditional Chinese medicine of important medicinal and economic value, sees increasing demand in medicinal and moxibustion product market. Screening stable and reliable reference genes for quantitative real-time PCR(qRT-PCR) is a prerequisite for the analysis of gene expression in Artemisia argyi. In this study, eight commonly used reference genes, Actin, 18s, EF-1α, GAPDH, SAND, PAL, TUA, and TUB, from the transcriptome of A. argyi, were selected as candidate genes. The expression of each gene in different tissues(roots, stems, and leaves) of A. argyi and in leaves of A. argyi after treatment with methyl jasmonate(MeJA) for different time(0, 4, 8, 12 h) was detected by qRT-PCR. Then, geNorm, NormFinder, BestKeeper, ΔCT, and RefFinder were employed to evaluate their expression stability. The results demonstrated that Actin was the most stable reference gene in different tissues and in leaves treated with MeJA, and coming in the second was SAND. Furthermore, the expression of DXS and MCT which are involved in terpenoid backbone biosynthesis was detected in different tissues and after MeJA treatment. The results showed that the expression patterns of DXS and MCT in different tissues and under MeJA treatment calculated with Actin and SAND as internal reference genes were consistent, which validated the screening results. In conclusion, Actin is the most suitable reference gene for the analysis of gene expression in different tissues of A. argyi and after MeJA treatment. This study provides valuable information for gene expression analysis in A. argyi and lays a foundation for further research on molecular mechanism of quality formation of Artemisia Argyi Folium.
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Artemisia/genetics , Gene Expression Profiling , Genes, Plant/genetics , Plant Leaves/genetics , Real-Time Polymerase Chain Reaction , Reference Standards , TranscriptomeABSTRACT
@#Objective To explore the predictive value of neutrophil/lymphocyte ratio (NLR) on the 90 day mortality risk of patients with cardiogenic cerebral embolism (CE).Methods 245 patients with cardiogenic cerebral embolism were analyzed retrospectively.Demographic data,vascular risk factors,laboratory tests and end point events were collected.The patients were divided into survival group and death group according to whether or not there were end-point events.Multifactor logistic regression was used to analyze the influencing factors of endpoint events,to draw ROC curve,and to evaluate the predictive value of NLR on endpoint events.Results Of the 245 cases included in the analysis,145 survived and 100 died.Compared with the survivors,the age,hyperlipidemia,atrial fibrillation,mRS score,white blood cell count,glutathione aminotransferase and neutrophil score in the death group were significantly higher (P<0.01),and there was no significant difference in gender,hypertension,diabetes,family history,smoking,alcohol consumption,red blood cell count,hemoglobin and other blood indicators between the two groups(P>0.05).Multivariate logistic regression analysis showed that age,atrial fibrillation,hyperlipidemia and NLR were independent risk factors for 90-day death.ROC shows AUC=0.7558.When the optimal cutoff value of NLR was 5.65,the sensitivity was 68.0%,and the specificity was 76.6%.Conclusion The increase of NLR at admission is a high risk factor for 90 day death in patients with cardiogenic cerebral infarction,and it has a good predictive value for 90 day death.
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@#To analyze the influencing factors and clinical significance of fatigue in patients with Parkinson’s disease(PD). Methods 155 patients with PD were selected from the Department of Neurology of the Second Affiliated Hospital of Baotou Medical College from January 2019 to December 2020.According to the fatigue severity scale(FSS),59 patients in the PD non fatigue group(FSS>4 points) and 96 patients in the PD fatigue group(FSS≤4 points). Unified Parkinson’s disease rating scale Part III(MDS-UPDRS Ⅲ)、Hoehn-Yahr(H-Y)、Hamilton Depression Scale(HAMA)17,Hamilton Anxiety Scale(HAMD)14,Parkinson’s disease Sleep Scale(PDSS) Chinese version,simple mental state scale and so on. The physical fatigue and mental fatigue of PD patients were scored by fatigue Scale-14(fs-14). The total scores of tremor items and postural abnormalities gait disorders were calculated according to the items of MDS UPDRS Ⅱ~Ⅲ. Results Compared with the non fatigue group,the mds-updrs Ⅲ,H-Y score,HAMA,HAMD and course of disease in the fatigue group were increased,and the PDSS was decreased(P<0.05). Mds-updrs Ⅲ score(OR=1.105,P=0.011) and depression(OR=1.160,P=0.028) were independent risk factors for fatigue. Mental fatigue was positively and strongly correlated with HAMD(rs=0.792);physical fatigue was positively and strongly correlated with mds-updrs Ⅲ(rs=0.645),total score of postural abnormalities gait disorders(rs=0.659),HAMA(rs=0.654) and H-Y score(rs=0.674),which was positively and strongly correlated with PDSS(rs=-0.674) negative strong correlation. Conclusion The incidence rate of fatigue in PD patients is high,and is associated with motor symptoms,sleep disorders,anxiety and depression.
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【Objective】 To further determine the relationship between blood donor role cognition and blood donation behavior, then prepare of blood donor role identity scale(BDRIS). 【Methods】 The preparation of the scale was divided into five stages. It includes literature retrieval, expert interview, construction of the basic framework of the scale, scale test and statistical index test. The study focused on items selection, dimensions identification, measurement reliability, content and structural validity. 【Results】 The blood donor role identity scale consisted of 35 items. Exploratory factor analysis divided the items into six common factors, including role identity, role expectation, current situation of blood collection and supply, role conflict, external reward and blood donation experience. The α of scale was 0.840. 【Conclusion】 The reliability and validity of the scale meet the basic measurement requirements, and the framework of the blood donor role scale is basically formed. It can be used as one of the means to explore the ways and mechanisms of the role identity of blood donors in blood donation behavior.
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Objective:To investigate the effect and mechanism of Yiqi Fuzheng Jiedu decoction (YQFZJDD) on autophagy and growth of A549 cells. Method:A549 cells were intervened with YQFZJDD-containing serum prepared in advance. The levels of microtubule-associated protein 1 light chain 3 (LC3), homologue of yeast autophagy-related gene 6 (Beclin1), p62, p53, adenosine 5'-monophosphate-activated protein kinase (AMPK), phosphorylated AMPK (p-AMPK), mammalian target of rapamycin (mTOR), and phosphorylated mTOR (p-mTOR) were detected by Western blot assay, and microtubule-associated protein 1A/1B light chain 3B (MAP1LC3B) by immunofluorescence (IF) assay. The proliferation, invasion, and senescence of A549 cells were separately measured by 5-ethynyl-2'-deoxyuridine (EDU) staining, Transwell assay, and <italic>β</italic>-galactosidase staining. In the presence of autophagy inhibitor 3-methyladenine (3-MA, 5 mmol·L<sup>-1</sup>), the cells were divided into the 10% fetal bovine serum (blank) group, 10% control serum (control) group, low-, medium-, and high-dose 10% YQFZJDD-containing serum groups, and high-dose 10% YQFZJDD-containing serum + 3-MA group, followed by the measurement of A549 cell proliferation, invasion, and senescence. In the adoption of p53 inhibitor Pifithrin-<italic>α</italic> (PFT-<italic>α</italic>, 10 μmol·L<sup>-1</sup>), the cells were divided into the control group, PFT-<italic>α</italic> group, high-dose YQFZJDD-containing serum group, and high-dose YQFZJDD-containing serum + PFT-<italic>α</italic> group. Then the LC3-Ⅱ and Beclin1 expression, MAP1LC3B fluorescence intensity, as well as A549 cell proliferation, invasion and senescence were determined. Result:Compared with the blank group and control group, YQFZJDD-containing serum at the medium and high doses up-regulated the protein expression levels of LC3-Ⅱ and Beclin1 in A549 cells after 48-h intervention in a dose-dependent manner (<italic>P</italic><0.01). Besides, YQFZJDD-containing serum at the low-, medium-, and high-doses down-regulated p62 and p-mTOR/mTOR expression (<italic>P</italic><0.05, <italic>P</italic><0.01), elevated p53 and p-AMPK/AMPK (<italic>P</italic><0.01), decreased the number of proliferative and invasive cells, increased the number of senescent cells (<italic>P</italic><0.01), and enhanced the IF intensity of MAP1LC3B, with the optimal effect observed in the high-dose YQFZJDD-containing serum group (<italic>P</italic><0.01). Compared with the high-dose YQFZJDD-containing serum group, the high-dose YQFZJDD-containing serum + 3-MA group and high-dose YQFZJDD-containing serum + PFT-<italic>α</italic> group exhibited significantly increased proliferative and invasive cells but decreased senescent cells (<italic>P</italic><0.05, <italic>P<</italic>0.01). Meanwhile, the IF intensity of MAP1LC3B in the high-dose YQFZJDD-containing serum + PFT-<italic>α</italic> group was weakened and the LC3-Ⅱ and Beclin1 protein expression levels declined (<italic>P</italic><0.05, <italic>P<</italic>0.01). Conclusion:YQFZJDD promotes the autophagy of A549 cells through the p53/AMPK signaling pathway to inhibit their proliferation, invasion and migration but accelerate senescence, thus playing a crucial role in inhibiting the progression of lung cancer.
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Objective To investigate the distribution and epidemiological characteristics of disease spectrum in patients with pre-hospital care in Urumqi, so as to provide reference for the establishment of mature pre-hospital care system. Methods Data retrieved from Urumqi Emergency Medical Center Command System were collected, and stratified random sampling method was used to selected 2400 patients from 8 districts and counties. The disease spectrum was analyzed, then the epidemiological characteristics was analyzed from the aspects of age, gender, season and aid time. Results The top 6 diseases were trauma in 696 cases (29.00%), cardiovascular disease in 521 cases (21.71%), poisoning in 328 cases (13.67%), respiratory system disease in 245 cases (10.21%), nervous system disease in 202 cases (8.42%) and digestive system disease in 139 cases (5.79%). Trauma and cardiovascular disease were the main types of pre-hospital care for both males and females, moreover, the incidence of trauma, nervous system disease, digestive system disease and other diseases in male was significantly higher than that in female (P<0.05). The distribution of trauma, cardiovascular and cerebrovascular disease, poisoning, respiratory disease, nervous system disease, digestive system disease and other diseases showed significant difference among patients in difference age groups (P<0.05). The distribution of trauma, cardiovascular and cerebrovascular diseases, poisoning, respiratory system diseases, nervous system disease and digestive system diseases showed significant difference in different seasons (P<0.05). The emergency calls in three shifts were the most on middle shift and were the least on night shift in Urumqi, accounting for 43.88%( 1 053 / 2 400) and 15.33% (368 / 2 400). Conclusion The distribution of disease types of pre-hospital care in Urumqi varies with gender, age, season and times, so relevant departments should improve the professional abilities of first aid and allocate first aid resources reasonably.
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Idiosyncratic drug-induced liver injury (IDILI) is an unpredictable serious adverse drug reaction, which only occurs in a minority of special susceptible individuals. Although the mechanism of IDILI has not been fully understood, several hypotheses have been proposed to explain the action mode and specific mechanism of IDILI. Of these hypotheses, inflammatory stress hypothesis is one of the most important theories. Under the condition of inflammatory stress, drugs interact with inflammation and mediate the occurrence of IDILI through a variety of mechanisms, which can induce the production of inflammatory cytokines, activate coagulation system, affect the activity of metabolites, induce cholestasis, affect mitochondrial damage, and others. This review will summarize the main mechanisms and influencing factors of IDILI mediated by inflammatory stress, in order to provide a reference for preclinical drug development and basic research on drug-induced liver injury.
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As recorded, agarwood has the function of improving qi reception and relieving asthma, but the underlying mechanism is unclear and rarely reported. Therefore, this study explored the anti-asthmatic effect of the alcohol extract of agarwood produced by the whole-tree agarwood-inducing technique(Agar-Wit) in the asthma mouse model induced by intraperitoneal injection of ovalbumin(OVA) + Al(OH)_3 combined with intranasal administration of OVA and the mechanism, and compared the anti-asthmatic effects of agarwood induced with different methods. Firstly, the anti-inflammatory and anti-asthmatic effects of Agar-Wit agarwood in mice were evaluated based on the asthma frequency, lung tissue injury, and peripheral inflammatory white blood cell(WBC) count and eosinophil count. Then, the levels of interleukin-1β(IL-1β), IL-17, and IL-10 in serum of mice were detected by enzyme-linked immunoassay(ELISA) and the expression of inflammation-and apoptosis-related genes in tissues was measured by reverse transcription polyme-rase chain reaction(RT-PCR) so as to preliminarily explore the anti-asthmatic mechanism. RESULTS:: showed that the alcohol extract of Agar-Wit agarwood significantly reduced asthma frequency, relieved pathological injury, improved peripheral WBC count and eosinophil count, decreased the levels of inflammatory cytokines IL-1β and IL-17, elevated the level of anti-inflammatory cytokine IL-10, and down-regulated the mRNA expression of IL-1 R, tumor necrosis factor receptor R(TNFR), nuclear transcription factor-kappa B(NF-κB), Bax, and caspase 3, but had no significant influence on the expression of high-mobility group box 1(HMGB1) protein, caspase 8, and Bcl-2. The effect of Agar-Wit agarwood alcohol extract was better than that of wild agarwood alcohol extract and alcohol extract of agarwood induced with the burning-chisel-drilling method at the same dose. In conclusion, Agar-Wit agarwood can significantly alleviate inflammation and asthma, which is related to its anti-inflammation and anti-apoptosis activity.
Subject(s)
Animals , Mice , Anti-Asthmatic Agents , Asthma/drug therapy , Bronchoalveolar Lavage Fluid , Disease Models, Animal , Lung , Mice, Inbred BALB C , NF-kappa B , Ovalbumin , Plant Extracts/therapeutic useABSTRACT
OBJECTIVE@#To summarize the experience in the application of muscle relaxants in the perioperative period in neonates with congenital esophageal atresia-tracheoesophageal fistula (EA-TEF).@*METHODS@#A retrospective analysis was performed on the medical data of 58 previously untreated neonates with EA-TEF who were treated in the Neonatal Center of Beijing Children's Hospital, Capital Medical University from 2017 to 2019. The incidence rate of anastomotic leak was compared between the neonates receiving muscle relaxants for different durations after surgery (≤ 5 days and > 5 days). The correlation between the duration of postoperative use of muscle relaxants and the duration of mechanical ventilation was evaluated.@*RESULTS@#Among the 58 neonates with EA-TEF, 44 underwent surgery, among whom 35 with type III EA-TEF underwent thoracoscopic surgery. Among these 35 neonates, 30 (86%) received muscle relaxants after surgery, with a median duration of 4.75 days, and 6 (18%) experienced anastomotic leak. There was no significant difference in the incidence rate of anastomosis leak between the ≤ 5 days and > 5 days groups (@*CONCLUSIONS@#Prolonged use of muscle relaxants after surgery cannot significantly reduce the incidence of anastomotic leak, but can prolong the duration of invasive mechanical ventilation in neonates with EA-TEF. Therefore, prolonged use of muscle relaxants is not recommended after surgery.
Subject(s)
Child , Humans , Infant, Newborn , Esophageal Atresia/surgery , Muscles , Postoperative Complications/etiology , Prognosis , Retrospective Studies , Tracheoesophageal Fistula/surgery , Treatment OutcomeABSTRACT
Psychiatric diseases represented by depression have gradually become one of the major health problems of people in the fast-paced, high-pressure society. Severe cases can cause suicides, huge harm or disaster to families and the society. Although modern medicine has made great progress in the field of anti-depressant drug therapy, depression still cannot be cured. At the same time, traditional Chinese medicines(TCM) with a definite curative effect, few adverse reactions, and mild efficacy have received increasing attention. TCM valerianae Jatanmansi Rhizoma et Radix has been widely used to alleviate sleep disorder, and its root extract is popularly known as valerian and used as a mild sedative for a long time in European. Tagara takes Valerianae Jatamansi Rhizoma et Radix as the key ingredient for treatment of depression-type insomnia, and is available abroad. It is reported that iridoid, sesquiterpenes, flavonoids or extract from Valerianae Jatamansi Rhizoma et Radix has a superior anti-depression activity in both animal and clinical trials, and the mechanism is mainly related to the regulation of neurotransmitters in the brain, the improvement of the function of the hypothalamic-pituitary-adrenal (HPA) axis, the resistance of free radicals and inflammation, and the neuroprotective effect. However, there is still lack of report on the anti-depression system and in-depth research of Valerianae Jatamansi Rhizoma et Radix. Therefore, it is urgently necessary to systematically collect and summarize the anti-depressant activity and explain the relevant mechanisms, so as to provide reference for the further development of Valerianae Jatamansi Rhizoma et Radix medicinal resources.
ABSTRACT
Objective:Metabolomics was used to analyze the brain tissue samples of model mice with chronic unpredictable mild stress (CUMS) depression, in order to find out the differential metabolites related to depression and to explore the possible antidepressant mechanism of iridoid part of Valerianae Jatamansi Rhizoma et Radix (IEFV). Method:Forty-two Kunming mice were randomly divided into 6 groups, including the normal group, the model group, the fluoxetine group (2.5 mg·kg-1) and the IEFV low, medium, and high dose groups (doses were 5.73, 11.47, 22.94 mg·kg-1, respectively). The behavioral and biochemical indicators of CUMS model mice were used for pharmacodynamic evaluation with IEFV and a positive drug (fluoxetine) as the intervention drugs. Then, the effect of IEFV on endogenous substances of the brain tissue in CUMS model mice were analyzed by nuclear magnetic resonance hydrogen spectrum (1H-NMR) metabolomics, and multivariate statistical analysis was used to identify the differential metabolites and to enrich the metabolic pathways involved in the differential metabolites. Result:After modeling, the immobility time of the model mice increased significantly, their sucrose preference rate and the excitatory neurotransmitters [5-hydroxytryptamine (5-HT) and norepinephrine (NE)] decreased significantly, indicating the success of modeling. The depression was relieved after IEFV administration, mainly manifested by the recovery of the immobility time, sucrose preference rate and the excitatory neurotransmitters (5-HT and NE). Principal component analysis (PCA) of endogenous metabolites in brain tissue showed that the model group could be significantly separated from the normal group, while the IEFV groups and fluoxetine group all showed a trend of deviating from the model group to the normal group, which was consistent with the behavioral results. The results of orthogonal partial least squares discriminant analysis (OPLS-DA) showed that there were 16 different metabolites between the model group and the normal group, including 12 water-soluble metabolites and 4 liposoluble metabolites. Seven potential metabolism pathways were obtained through MetPA analysis, including metabolism of phenylalanine, metabolism of phenylalanine, tyrosine and tryptophan, metabolism of taurine and hypotaurine acid, metabolism of alanine, aspartic acid and glutamic acid, biosynthesis of valine, leucine and isoleucine, metabolism of D-glutamine and D-glutamate and tricarboxylic acid cycle (TCA). IEFV-high dose group could significantly recall 11 differential metabolites. Conclusion:IEFV may play an antidepressant role mainly by affecting energy metabolism, amino acid metabolism and neurotransmitter levels, which provides a reference for further study on the antidepressant mechanism of IEFV.