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Objective:To explore the evaluation of 256 slice spiral computed tomography angiography(CTA)of coronary,serum lipoprotein associated phospholipase A2(Lp-PLA2)and angiopoietin like protein 3(ANGPTL3)on the severity of coronary artery stenosis of patients with coronary heart disease.Methods:A total of 102 patients with coronary heart disease who were diagnosed and treated at Hebei Chest Hospital from July 2022 to March 2023 were selected as the study subjects.According to the Gensini score about the severity of coronary artery stenosis,they were divided into mild stenosis group(0 score≤Gensini score≤20 scores),moderate stenosis group(20 scores<Gensini score≤60 scores)and severe stenosis group(Gensini score>60 scores),with 34 cases in each group.The minimum lumen diameter(MLD),percentage of area of stenosis(%AS),percentage of diameter of stenosis(%DS),minimum lumen area(MLA),Lp-PLA2 and ANGPTL3 among three groups were compared.The diagnostic efficiency of the severity of coronary artery stenosis was predicted according to receiver operating characteristic(ROC)curve.Results:The MLA and MLD values in severe stenosis group were significantly lower than those in moderate and mild stenosis groups,while%AS and%DS were significantly higher than those in moderate and mild stenosis groups(t=6.905,4.083,5.871,6.976,3.387,2.198,2.668,3.505,P<0.05),respectively.The Lp-PLA2 and ANGPTL3 values in severe stenosis group were significantly higher than those in moderate and mild stenosis groups(t=4.164,8.220,2.575,3.050,P<0.05),respectively.ROC curve analysis showed that the area under curve(AUC)values of MLA,MLD,%AS,%DS,CCTA comprehensive parameter,LpPLA2 and ANGPTL3 were respectively were 0.838,0.690,0.742,0.801,0.904,0.808 and 0.807 in predicting the severity of coronary artery stenosis.The sensitivities of them were respectively 91.20%,91.20%,64.70%,94.10%,97.10%,70.60%and 88.20%.The specificities of them were respectively 76.50%,57.40%,75.00%,50.00%,70.60%,97.10%and 70.60%.The AUC value of CCTA comprehensive parameter was respectively higher than that of LpPLA2 and ANGPTL3,but the difference was not statistically significant(P>0.05).Conclusion:256 slice spiral CCTA,serum Lp-PLA2 and ANGPTL3 have a certain efficiency in assessing the severity of coronary artery stenosis of coronary heart disease,and 256 slice spiral CCTA has higher predictive efficiency.
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Objective: To investigate the drug-resistant gene characteristics and core genome characteristics of carbapenem-resistant Enterobacter cloacae (CR-ECL) in rural residents of Weifang City, Shandong Province. Methods: Fecal samples were collected from rural community residents in Weifang City, Shandong Province in 2017. Drug-resistant strains were screened using a carbapenem-resistant enterobacter chromogenic medium. CR-ECL positive strains were acquired via Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry(MALDI-TOFMS) analysis. The antibiotic resistance phenotype of CR-ECL was determined using a microbroth dilution assay. Whole genome sequencing (WGS) and analysis were conducted, along with an examination of the immediate vicinity of the blaNDM gene and phylogenetic analysis of the strains. Results: A total of 628 fecal samples were collected and tested, of which 6 were CR-ECL positive (detection rate 0.96%), all exhibiting multiple drug resistance (MDR) phenotypes. Six CR-ECL strains had four MLST genotypes (ST), all of which carried multiple drug resistance genes (blaNDM-1, blaNDM-5, etc.) and virulence genes (acrA, acrB, entB, fepC, etc.). There were mobile genetic elements ISAba125, TN3-IS3000, TN3 and IS5 in the genetic environment surrounding the blaNDM gene. The phylogenetic tree showed that the multi-locus sequence typing of the core genome (cgMLST) was consistent with the single nucleotide polymorphism (SNPs) results. The cgMLST results showed that the allele differences between strains 2BC0101B and 2BC0251B, 2BG0561B and 2BI0221B were 2 and 1, respectively. The SNPs results showed that the above two pairs of bacteria also clustered together. It was found that the strains of chicken fecal samples in the National Center for Biotechnology Information (NCBI) database were located in the center of the evolutionary tree, and the local sequences could be traced back to American human sequences. Conclusion: Multidrug-resistant CR-ECL is detected in rural community residents in Weifang City, Shandong Province.
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Humans , Anti-Bacterial Agents/therapeutic use , Enterobacter cloacae/genetics , Multilocus Sequence Typing , beta-Lactamases/genetics , Phylogeny , Rural Population , Carbapenems/pharmacology , Microbial Sensitivity TestsРеферат
Objective: To investigate the drug-resistant gene characteristics and core genome characteristics of carbapenem-resistant Enterobacter cloacae (CR-ECL) in rural residents of Weifang City, Shandong Province. Methods: Fecal samples were collected from rural community residents in Weifang City, Shandong Province in 2017. Drug-resistant strains were screened using a carbapenem-resistant enterobacter chromogenic medium. CR-ECL positive strains were acquired via Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry(MALDI-TOFMS) analysis. The antibiotic resistance phenotype of CR-ECL was determined using a microbroth dilution assay. Whole genome sequencing (WGS) and analysis were conducted, along with an examination of the immediate vicinity of the blaNDM gene and phylogenetic analysis of the strains. Results: A total of 628 fecal samples were collected and tested, of which 6 were CR-ECL positive (detection rate 0.96%), all exhibiting multiple drug resistance (MDR) phenotypes. Six CR-ECL strains had four MLST genotypes (ST), all of which carried multiple drug resistance genes (blaNDM-1, blaNDM-5, etc.) and virulence genes (acrA, acrB, entB, fepC, etc.). There were mobile genetic elements ISAba125, TN3-IS3000, TN3 and IS5 in the genetic environment surrounding the blaNDM gene. The phylogenetic tree showed that the multi-locus sequence typing of the core genome (cgMLST) was consistent with the single nucleotide polymorphism (SNPs) results. The cgMLST results showed that the allele differences between strains 2BC0101B and 2BC0251B, 2BG0561B and 2BI0221B were 2 and 1, respectively. The SNPs results showed that the above two pairs of bacteria also clustered together. It was found that the strains of chicken fecal samples in the National Center for Biotechnology Information (NCBI) database were located in the center of the evolutionary tree, and the local sequences could be traced back to American human sequences. Conclusion: Multidrug-resistant CR-ECL is detected in rural community residents in Weifang City, Shandong Province.
Тема - темы
Humans , Anti-Bacterial Agents/therapeutic use , Enterobacter cloacae/genetics , Multilocus Sequence Typing , beta-Lactamases/genetics , Phylogeny , Rural Population , Carbapenems/pharmacology , Microbial Sensitivity TestsРеферат
The cognition and attitude of scientific research ethics consciousness affect the willingness and degree of individual researchers to follow research ethics norms. This study investigated the awareness, access and training needs of Chinese medical researchers (n=11 164) on the knowledge of scientific research ethics. The survey found that more than 50.0% of people were aware of the "golden rice incident" and "skull transplantation"; 80.0% of people were knew of Operational Quideline for the Ethic Review of Biomedical Research Involving Human Subject; 90.0% said that "respecting people" and "not harming" were the basic ethical principles, but 42.8% and 75.1% chose "beneficial" and "fair" respectively; more than 60.0% of people have acquired scientific research ethics knowledge through "self-study", "special training organized by units" or "words and deeds taught by mentors or colleagues", but still 30.0% have not participated in scientific research ethics lectures in recent three years; In terms of training needs, more than 50.0% chose "ethical norms for research and application", followed by "frontier ethical issues" (41.0%) and "ethical review" (36.7%). Based on this, this paper puts forward some suggestions to improve the content and form of scientific research ethics education and training in China.
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Objective:To summarize the characteristics of autosomal recessive axonal neuropathy with neuromyotonia (ARAN-NM) caused by HINT1 gene mutation. Methods:Retrospective case summary.Clinical data of 2 Tibetan siblings diagnosed with ARAN-NM in the Department of Pediatrics of Peking University First Hospital in August 2023 were retrospectively analyzed.A review of literature reporting relevant Chinese patients was conducted.Results:The proband and her elder brother were aged 13 and 19, respectively.Both developed abnormal gait at the age of 11, followed by varus, claudication, and weak thumb strength.The proband also had neuromyotonia.Physical examinations showed that the proband and her elder brother had decreased muscle strength of the extremities, mainly in the thumbs and distal ends of lower limbs.The distal muscles of the proband′s lower extremities and the muscles of both hands of the proband′s elder brother were atrophied.Both feet showed talipes equinovarus in the proband and her elder brother.The proband′s electromyography (EMG) showed peripheral nerve injuries (motor and sensory axonal involvement, especially in distal ends) and myotonic potentials.The trio-whole exon sequencing detected homozygous pathogenic variation in HINT1 gene in both the proband and her elder brother, who were diagnosed as ARAN-NM based on c. 169A>G (p.K57E). After the Carbamazepine treatment, the proband′s neuromyotonia, numbness and weakness were relieved.Both the proband and her elder brother underwent orthopaedic surgery and rehabilitation.Their foot deformities and gait were significantly improved.Two Chinese literatures (2 patients) and four English literatures (8 patients) were retrieved.Including the proband and her elder brother in this study, there were 12 ARAN-NM patients, 10 of whom had clinical data.The ages of onset and diagnosis were 2-16 (1 case unknown) and 13-33 years old, respectively.Myasthenia was present in 9 patients, especially in distal ends.Eight patients were complicated with neuromyotonia, nine patients with muscle atrophy, seven patients with foot deformity, and two patients with sensory disturbance.Creatine kinase(CK) was elevated in all 9 patients tested or CK.EMG showed neurogenic injuries in all patients and neuromyotonia discharge in six patients.Three patients were treated with Carbamazepine, and some symptoms were relieved.Missense/nonsense mutations were found in the 12 patients, and the high-frequency variation was c. 112T>C (p.C38R). Conclusions:ARAN-NM is a rare autosomal recessive neuromuscular disease caused by HINT1 gene mutation.There is no ethnic difference in clinical manifestations, mainly distal limb weakness with neuromyotonia.Carbamazepine can alleviate some symptoms, and orthopaedic surgery can improve foot deformity and gait.
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BACKGROUND:Cardiac hypertrophy is an adaptive response of the heart to physiological and pathological stimuli such as pressure overload.It is of compensatory significance in the early stage,but if the stimulation continues,it can cause cardiomyopathy leading to heart failure.MicroRNAs are involved in the regulation of cardiac hypertrophy.However,the role of miR-20a in pressure overload-induced cardiac hypertrophy has not been reported. OBJECTIVE:To investigate the role of miR-20a in pressure overload-induced cardiac hypertrophy and the underlying mechanisms. METHODS:Transverse aortic constriction was used to induce cardiac hypertrophy in vivo and angiotensin Ⅱ was used to induce H9c2 cell models of cardiac hypertrophy in vitro.MiR-20a was overexpressed in vivo by intramyocardial injection of miR-20a overexpressing adenovirus and in vitro by transfecting miR-20a mimic into H9c2 cells.Cardiac hypertrophy was assessed by measuring heart weight/body weight ratio,cell surface area,and myocardial fibrosis.The expression levels of atrial natriuretic peptide,brain natriuretic peptide,β-myosin heavy chain and miR-20a were detected by real-time fluorescence quantitative PCR.Mitochondrial fission was detected by MitoTracker.The downstream target genes of miR-20a were predicted by RNAhybrid software. RESULTS AND CONCLUSION:(1)The expression level of miR-20a was significantly decreased in both hypertrophic cardiomyocytes and hearts(P<0.05).(2)At the animal level,overexpression of miR-20a significantly inhibited transverse aortic constriction-induced cardiac hypertrophy,including decreasing the upregulated expression level of hypertrophic marker genes(P<0.05),reduced the enlarged heart volume,reducing the increased heart weight/body weight ratio(P<0.01),reducing the increased myocardial cross-sectional area(P<0.05),and attenuating fibrosis(P<0.01).(3)At the cellular level,overexpression of miR-20a significantly inhibited angiotensin Ⅱ-induced cardiomyocyte hypertrophy,including decreasing the upregulated expression levels of atrial natriuretic peptide(P<0.05),brain natriuretic peptide(P<0.01)and β-myosin heavy chain(P<0.05),reducing the increased protein/DNA ratio(P<0.01),and suppressing the increased cell surface area(P<0.05).(4)Overexpression of miR-20a significantly inhibited angiotensin Ⅱ-induced mitochondrial fission(P<0.05).(5)The results of RNAhybrid software analysis showed that miR-20a and the mRNA 3'untranslated region of cAMP-dependent protein kinase inhibitor alpha were well complementary and the predicted binding sites were highly conserved.(6)In conclusion,miR-20a is significantly down-regulated in pressure overload-induced cardiac hypertrophy.Overexpression of miR-20a inhibits cardiac hypertrophy at both the cellular level and animal level and attenuates angiotensin Ⅱ-induced mitochondrial fission.
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TCP family as plant specific transcription factor, plays an important role in different aspects of plant development. In order to screen TCP family members in tobacco, the homologous sequences of tobacco and Arabidopsis TCP family were identified by genome-wide homologous alignment. The physicochemical properties, phylogenetic relationships and cis-acting elements were analyzed by bioinformatics. The homologous genes of AtTCP3/AtTCP4 were screened, and RT-qPCR was used to detect the changes of gene expression upon 20% PEG6000 treatment. The results show that tobacco contains 63 TCP family members. Their amino acid sequence length ranged from 89 aa to 596 aa, and their protein hydropathicity grand average of hydropathicity (GRAVY) ranged from -1.147 to 0.125. The isoelectric point (pI) ranges from 4.42 to 9.94, the number of introns is 0 to 3, and the subcellular location is all located in the nucleus. The results of conserved domain and phylogenetic relationship analysis showed that the tobacco TCP family can be divided into PCF, CIN and CYC/TB1 subfamilies, and each subfamily has a stable sequence. The results of cis-acting elements in gene promoter region showed that TCP family genes contain low docile acting elements (LTR) and a variety of stress and metabolic regulation related elements (MYB, MYC). Analysis of gene expression patterns showed that AtTCP3/AtTCP4 homologous genes (NtTCP6, NtTCP28, NtTCP30, NtTCP33, NtTCP42, NtTCP57, NtTCP63) accounted for 20% PEG6000 treatment significantly up-regulated/down-regulated expression, and NtTCP30 and NtTCP57 genes were selected as candidate genes in response to drought. The results of this study analyzed the TCP family in the tobacco genome and provided candidate genes for the study of drought-resistance gene function and variety breeding in tobacco.
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Nicotiana/genetics , Phylogeny , Plant Breeding , Amino Acid Sequence , Arabidopsis , Polyethylene GlycolsРеферат
Since the first operational definition of cognitive frailty was proposed by the expert consensus group of the International Academy of Nutrition and Aging and the International Association of Gerontology and Geriatrics in 2013, frailty and neurocognitive assessment has become the standard diagnostic tool.Since then, the reported prevalence in the literature for cognitive frailty in community-dwelling elderly people vary by dozens of times, as a result of different scales and diagnostic cut-off points, seriously affecting health decision-making.This article reviewed the current literature with a focus on the re-recognition of the clinical significance of cognitive frailty, the limitations of existing assessment tools for diagnosis, and possible solutions in the future.
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Purpose@#The purpose of this study was to use data mining methods to establish a simple and reliable predictive model based on the risk factors related to gallbladder stones (GS) to assist in their diagnosis and reduce medical costs. @*Materials and Methods@#This was a retrospective cross-sectional study. A total of 4215 participants underwent annual health examinations between January 2019 and December 2019 at the Physical Examination Center of Shengjing Hospital Affiliated to China Medical University. After rigorous data screening, the records of 2105 medical examiners were included for the construction of J48, multilayer perceptron (MLP), Bayes Net, and Naïve Bayes algorithms. A ten-fold cross-validation method was used to verify the recognition model and determine the best classification algorithm for GS. @*Results@#The performance of these models was evaluated using metrics of accuracy, precision, recall, F-measure, and area under the receiver operating characteristic curve. Comparison of the F-measure for each algorithm revealed that the F-measure values for MLP and J48 (0.867 and 0.858, respectively) were not statistically significantly different (p>0.05), although they were significantly higher than the F-measure values for Bayes Net and Naïve Bayes (0.824 and 0.831, respectively; p<0.05). @*Conclusion@#The results of this study showed that MLP and J48 algorithms are effective at screening individuals for the risk of GS.The key attributes of data mining can further promote the prevention of GS through targeted community intervention, improve the outcome of GS, and reduce the burden on the medical system.
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OBJECTIVE To study the quality of Codonopsis pilosula with different commodity specification grades, and to provide the data support for market transactions, scientific research and clinical use. METHODS According to the classification standard of commodity specification grades of C. pilosula, 17 batches of C. pilosula from different producing areas, origins and commodity specification grades were collected. The contents of tangshenoside Ⅰ, lobetyolin and atractylenolide Ⅲ were determined by HPLC. The contents of alcohol-soluble extracts were determined by hot dipping method stated in general rule 2201 of Chinese Pharmacopeia (part Ⅳ). The contents of polysaccharide were determined by phenol-sulfuric acid method (calculated by D-glucose anhydrous). RESULTS For cultivar of C. pilosula, four specifications and three commodity grades of C. pilosula all contained tangshenoside Ⅰ and lobetyolin; Radix C. pilosula from Shanxi of China and C. pilosula from Wenxian County of China, also contained atractylenolide Ⅲ. In terms of the contents of tangshenoside Ⅰ, lobetyolin and atractylenolide Ⅲ, the content of second class was equivalent to that of first class, even better than the first class, while the content of third class was lower than that of first class and second class; the content of tangshenoside Ⅰ was the highest among the two types of wild C. pilosula. The contents of alcohol-soluble extracts and polysaccharides in first class cultivated C. pilosula were higher than those of second class, and the second class was higher than the third class; wild C. pilosula had low content of alcohol-soluble extracts and polysaccharides. CONCLUSIONS The internal quality of C. pilosula is basically consistent with the classification standard of different commodity specification grades; the content of each indicator in first-class and second-class medicinal herb is high, making them high-quality medicinal herbs.
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Objective:To explore the clinical features of Mycoplasma pneumoniae(MP)infection in children, and provide data support for the prevention and control of MP.Methods:In this study , a retrospective analysis was used to collect clinical data with respiratory tract infection from January 2018 to February 2022 in the Shenyang Children′s Hospital, and analyze the distribution characteristics of MP positive rate, season, age, sex.Results:In this study, the positive rate of MP was 17.12% (20 299/118 598), in 2018, 2019, 2020 and 2021 were 22.92% (7 732/33 738), 15.76% (5 736/36 388), 9.81% (1 313/13 379) and 16.60% (4 954/29 849) respectively.The highest positive rates of MP in 2018 and 2019 were 27.72% (1 809/6 527) and 23.45% (1 519/6 478) in summer, respectively, 2020 was spring (19.13%, 216/1 129) and 2021 was autumn (20.09%, 1 665/8 287).The MP positive rates of infancy, early childhood, preschool age and school age were 5.89% (605/10 265), 14.35% (4 639/32 333), 18.51% (10 961/59 203) and 24.37% (4 094/16 798), and MP positive rate increased with age, the difference was statistically significant ( χ2=1 790.971, P<0.05).The positive rate of boys was 14.70% (9 586/65 206), while that of girls was 20.06% (10 713/53 392), the difference was statistically significant ( χ2=594.937, P<0.05). Conclusion:MP can occur all years round, mainly in summer and autumn.Girls are susceptible, especially common in school-age and pre-school children.Prevention and control measures should be taken as soon as possible for susceptible individuals to reduce the infection rate of MP.
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Objective:To analyze the cause and epidemiological characteristics of an outbreak of cutaneous anthrax in Caoxian County, Heze City, Shandong Province, and to provide scientific basis for anthrax prevention and control.Methods:Using on-site epidemiological investigation methods and the "Anthrax Epidemiological Case Investigation Form", case investigations were conducted based on the epidemiological contact history and close contacts of suspected anthrax cases reported by the national health care system ( n = 83). Scorched skin smears, diseased cattle tissues, soil samples from the slaughter site and smears from slaughter utensils were collected from cases for Real-time PCR testing and pathogenic bacteria isolation and culture, respectively. Anthrax determination criteria were carried out with reference to "Anthrax Diagnosis" (WS 283-2020). Results:A total of 13 cases of cutaneous anthrax were found in this outbreak, including 12 clinically diagnosed cases and one confirmed case (positive Real-time PCR test and isolation of a strain of Bacillus anthracis). The epidemiological investigation determined that the source of infection in this outbreak was diseased cattle, the transmission route was through slaughter of diseased cattle, contact with contaminated utensils and related cattle products, and the patients were mainly engaged in occupations related to cattle slaughter or cattle product collection and sale. A total of 84 samples were collected, including 13 skin scabs, 64 environmental samples and 7 beef samples. Thirty-six positive PCR tests were performed, with a positive rate of 42.86% (36/84). Among them, 100.00% (13/13) were positive for skin scab smear specimens, 29.69% (19/64) for environmental samples and 4/7 for beef samples. A total of 8 strains of Bacillus anthracis were isolated, including 6 environmental specimens, 1 suspected case and 1 beef strain, with an overall detection rate of 9.52% (8/84). Eighty-three close contacts were investigated. Thirteen households involved in the epidemic were disinfected by spraying (200 ml/m 2) with chlorine-containing disinfectant (5 000 mg/L), and a total of 40 households involved in the epidemic were disinfected, covering an area of about 10 765 m 2. Forty-five pieces of suspected contaminated clothing were burned and disposed of, and 152 pieces of kitchenware were soaked. Conclusions:Slaughter of infected cattle, contact with contaminated utensils and related cattle products are the main causes of this skin anthrax outbreak. Strengthening market supervision, deepening inter-animal epidemic prevention, carrying out publicity and education on anthrax prevention and control, and enhancing practitioners' awareness of disease prevention is the key to prevent anthrax from occurring.
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Objective:Sepsis is a life-threatening organ dysfunction caused by the host's imbalanced response to infection.Due to lack of effective treatments,it has always been the difficulty and focus of clinical treatment of sepsis.Studies have shown that pro-brain-derived neurotrophic factor(proBDNF)binds to the high-affinity total neurotrophic factor p75 neurotrophin receptor(p75NTR),which activates downstream signaling cascades and disrupts immunological inflammation and plays an important role in the progression of sepsis.This study aims to explore the expression changes of lymphocyte-derived proBDNF/p75NTR in patients with sepsis and its effect on lymphocyte differentiation. Methods:From the healthy donors(control group,n=40)and sepsis patients(sepsis group,n=40)admitted to the hospital for the first time,peripheral blood samples and blood routine clinical detection indicators were obtained.By using flow cytometry,the proportion of lymphocyte subsets and their expression of proBDNF/p75NTR were examined.The peripheral blood lymphocytes were isolated from the control group and incubated with lipopolysaccharide(LPS).Flow cytometry analysis technology was used to detect the expression of proBDNF/p75NTR on LPS-treated lymphocyte subsets.On this basis,we investigated the effects on lymphocyte differentiation by inhibiting p75NTR. Results:White blood cell count,neutrophil count,and neutrophil percentage of the patients in the sepsis group at admission were significantly higher than those in the control group;on the contrary,lymphocyte count and lymphocyte percentage in the sepsis group were lower than those in the control group(all P<0.001).The patients in the sepsis group had considerably greater neutrophil/lymphocyte and monocyte/lymphocyte ratios than those in the control group(both P<0.05).In the peripheral blood of sepsis patients,proBDNF expression was upregulated on CD19+ B cells,whereas p75NTR expression was elevated on B cells,CD4+ T cells,and CD8+ T cells(all P<0.05).ProBDNF/p75NTR expression was upregulated by LPS stimulation in vitro in peripheral blood cells of the control group(P<0.05),and this tendency was similar to the expression alterations in peripheral lymphocytes of the sepsis group.Inhibition of p75NTR increased CD4+ T cell and CD19+ B cell percentages,cytokine expression of IL-4 and IL-10,and reduced IL-1β and IL-6 production(all P<0.05). Conclusion:The immunosuppressive state of sepsis patients is indicated by a reduction in lymphocyte count and an increase in the proportion of inactive neutrophils.ProBDNF/p75NTR expression is upregulated in the peripheral blood lymphocytes of sepsis patients,and p75NTR inhibition may control lymphocyte differentiation involved in sepsis progression.
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Objective:Sepsis-associated cognitive dysfunction is a common complication in patients with sepsis and lack of effective treatment.Its pathological mechanisms remain unclear.Salt-induced kinase(SIK)is an important molecule in the regulation of metabolism,immunity,and inflammatory response.It is associated with the development of many neurological diseases.This study aims to investigate the expression of SIK in the hippocampus of septic mice,and to evaluate the role and mechanism of the SIK inhibitor HG-9-91-01 in sepsis-associated cognitive dysfunction. Methods:Firstly,C57BL/6 mice were randomly divided into a control group(Con group)and a sepsis model group[lipopolysaccharide(LPS)group].The model group was injected intraperitoneally with LPS at a dose of 8 mg/kg and the Con group was injected with an equal volume of normal saline.Hippocampal tissues were harvested at 1,3,and 6 days after injection and the expressions of SIK1,SIK2,and SIK3 were detected by real-time fluorescence quantitative PCR(qPCR)and Western blotting.Secondly,C57BL/6 mice were randomly divided into a Con group,a LPS group,and a SIK inhibitor group(HG group).The LPS and HG groups were injected with LPS to establish a sepsis model;in the HG group,HG-9-91-01(10 mg/kg)was injected intraperitoneally at 3-6 days after LPS injection,and the LPS group was injected with the same volume of vehicle.Cognitive function was assessed at 7-11 days after LPS injection using the Morris water maze(MWM).Hippocampal tissues were harvested after the behavioral tests,and the mRNA levels of inflammatory factors and microglial markers were assessed by qPCR.The protein levels of inducible nitric oxide synthase(iNOS),CD68,ionized calcium binding adaptor molecule 1(Iba-1),N-methyl-D-aspartate(NMDA)receptor(NR)subunit,cAMP response element-binding protein(CREB)-regulated transcription coactivator 1(CRTC1),and insulin-like growth factor 1(IGF-1)were detected by Western blotting.Immunohistochemistry(IHC)was used to detect the expression of Iba-1 positive cells in the CA1,CA3 and dentate gyrus(DG)of the hippocampus,followed by Sholl analysis. Results:Compared with the Con group,the mRNA and protein levels of SIK1,SIK2,and SIK3 in the hippocampus were increased in the LPS group(all P<0.05).Compared with the Con group,mice in the LPS group had a significantly longer escape latency,a lower percentage of target quadrant dwell time and a reduced locomotor speed(all P<0.05);the HG group had a decreased escape latency and an increased percentage of time spent in the target quadrant in comparison with the LPS group(both P<0.05).The mRNA levels of inflammatory factors[tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6)],and the M1-type microglial markers iNOS and CD68 in the hippocampus of the LPS group were increased in comparison with the Con group,while the M2-type microglial markers CD206 and arginase-1(Arg-1)were decreased.Compared with the LPS group,the mRNA levels of TNF-α,IL-1β,IL-6,and iNOS were downregulated,while the levels of CD206 and Arg-1 were upregulated in the HG group(all P<0.05).The protein levels of iNOS,CD68,and Iba-1 in the hippocampus of the LPS group were increased in comparison with the Con group,but they were downregulated in the HG group in comparison with the LPS group(all P<0.05).The number of Iba-1 positive cells in CA1,CA3,and DG of the hippocampus was increased in the LPS group in comparison with the Con group,but they were decreased in the HG group in comparison with the LPS group(all P<0.05).Sholl analysis showed that the number of intersections at all radii between 8-38 μm from the microglial soma was decreased in the LPS group in comparison with the Con group(all P<0.05).Compared with the LPS group,the number of intersections at all radii between 14-20 μm was significantly increased in the HG group(all P<0.05).The protein levels of NR subunit NR1,NR2A,NR2B,and IGF-1 were downregulated in the hippocampus of the LPS group in comparison with the Con group,while the expression of phosphorylated CRTC1(p-CRTC1)was increased.Compared with the LPS group,the levels of NR1,NR2A,NR2B,and IGF-1 were upregulated,while p-CRTC1 was downregulated in the HG group(all P<0.05). Conclusion:SIK expression is upregulated in the hippocampus of septic mice.The SIK inhibitor HG-9-91-01 ameliorates sepsis-associated cognitive dysfunction in mice,and the mechanism may involve in the activation of the CRTC1/IGF-1 pathway,inhibition of neuroinflammation,and enhancement of synaptic plasticity.
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Purpose/Significance To construct the ontology model of breast cancer knowledge graph,and to realize the structured expres-sion and visual display of breast cancer knowledge.Method/Processs Breast cancer knowledge is extracted and represented,and the ontology model of breast cancer knowledge graph is constructed by Protégé software.The model includes 5 types of entities including patient,basic infor-mation of patient,inspection,diagnosis and attribute value of inspection,and more than 10 kinds of relationships such as having,examining,diagnosing,belonging and so on.Result/Conclusion The graphical display of breast cancer knowledge helps to improve the public's attention and understanding of breast cancer,and has a positive effect on the prevention and health management of breast cancer.
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Objective To investigate the immunomodulatory effect of mare's milk on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice. Methods Kunming mice were randomly divided into a blank group(0.8 mL/day saline by gavage) and a DSS modeling group. After modeling, the DSS modeling group was further divided into a control group (0.8 mL/day saline), a salazosulfapyridine (SASP) treated group(430 mg/(kg.d)) and a mare's milk group(0.8 mL/day), with 16 mice in each group. After 10 days of gavage administration, HE staining was performed to observe colonic inflammation, and the disease activity index (DAI) and colonic mucosal damage index (CMDI) were scored. ELISA was used to determine the levels of interleukin 1β (IL-1β), IL-6, and IL-10 in mouse colonic tissues, and flow cytometry was used to detect the percentages of CD4+ and CD8+ T lymphocytes in peripheral blood. Results Compared to the blank group, all indexes in mice of the control group indicated that DSS successfully induced UC. Compared to the control group, colon shortening in UC mice was attenuated in the mare's milk group; inflammation and ulcer formation in colonic tissues were inhibited; DAI and CMDI scores were lowere; IL-1β and IL-6 levels in mouse colonic tissues were significantly reduced; IL-10 levels were increased and the CD4+/CD8+ T cell ratio was reduced. Conclusion Mare's milk can inhibit the inflammation of DSS-induced UC mice through immune regulation.
Тема - темы
Mice , Animals , Female , Horses , Colitis, Ulcerative/drug therapy , Interleukin-10 , Dextran Sulfate , Interleukin-6 , Milk , Signal Transduction , Disease Models, Animal , Inflammation , ColonРеферат
Objective: To investigate the clinical features and gene variation characteristics of children with dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene associated spinal muscular atrophy with lower extremity predominant (SMALED) 1. Methods: The clinical data of 4 SMALED1 children admitted to Peking University First Hospital from December 2018 to May 2021, who were found to have pathogenic variation of DYNC1H1 gene through genetic testing, except for other genes known to be related to motor retardation, were retrospectively summarized to analyze the phenotype and genotype characteristics. Results: There were 3 males and 1 female. The age of onset was 1 year, 1 day, 1 day and 4 months, respectively. The age of diagnosis was 4 years and 10 months, 9 months, 5 years and 9 months, and 3 years and 1 month, respectively. The clinical manifestations were muscle weakness and muscular atrophy of lower limbs, 2 cases with foot deformity, 1 case with early non progressive joint contracture, 1 case with hip dislocation and 1 case with mental retardation. De novo heterozygous missense variations in DYNC1H1 gene were found in all 4 children. According to the rating of American College of medical genetics and genomics, they were all possible pathogenic and pathogenic variations, with p.R598C, p.P776L, p.Y1109D variations had been reported, and p.I1086R variation had not been reported. Conclusions: For those with unexplained lower limb muscle weakness, muscle atrophy, joint contracture and foot deformity, upper limb motor ability related retention, with or without mental retardation, as well as the motor ability progresses slowly, it is necessary to consider the possibility of SMALED1 and the detection of DYNC1H1 gene when necessary.
Тема - темы
Female , Male , Humans , Intellectual Disability , Retrospective Studies , Muscular Atrophy, Spinal/genetics , Lower Extremity , Muscle Weakness , Muscular Atrophy , Contracture , Cytoplasmic Dyneins/geneticsРеферат
Intervertebral disc degeneration (IDD) is one of the main diseases causing low back pain,which seriously affects the quality of life of patients.Recent studies have discovered that interleukin-6 (IL-6) is highly expressed in the tissues and cells of degenerative intervertebral disc and is closely related to the occurrence and development of IDD.However,the signaling pathway and role of IL-6 in IDD remain to be understood.Therefore,this article reviews the recent studies about the signaling pathway and role of IL-6 in IDD,aiming to facilitate the clinical work and subsequent research progress.
Тема - темы
Humans , Interleukin-6 , Intervertebral Disc Degeneration , Quality of Life , PeptidesРеферат
OBJECTIVES@#To investigate the distribution characteristics of non-bacterial pathogens in community-acquired pneumonia (CAP) in children.@*METHODS@#A total of 1 788 CAP children admitted to Shenyang Children's Hospital from December 2021 to November 2022 were selected. Multiple RT-PCR and capillary electrophoresis were used to detect 10 viral pathogens and 2 atypical pathogens, and serum antibodies of Chlamydial pneumoniae (Ch) and Mycoplasma pneumoniae (MP) were detected. The distribution characteristics of different pathogens were analyzed.@*RESULTS@#Among the 1 788 CAP children, 1 295 children were pathogen-positive, with a positive rate of 72.43% (1 295/1 788), including a viral pathogen positive rate of 59.68% (1 067/1 788) and an atypical pathogen positive rate of 22.04% (394/1 788). The positive rates from high to low were MP, respiratory syncytial virus (RSV), influenza B virus (IVB), human metapneumovirus (HMPV), human rhinovirus (HRV), human parainfluenza virus (HPIV), influenza A virus (IVA), bocavirus (BoV), human adenovirus (HADV), Ch, and human coronavirus (HCOV). RSV and MP were the main pathogens in spring; MP had the highest positive rate in summer, followed by IVA; HMPV had the highest positive rate in autumn; IVB and RSV were the main pathogens in winter. The positive rate of MP in girls was higher than that in boys (P<0.05), and there were no significant differences in other pathogens between genders (P>0.05). The positivity rates of certain pathogens differed among age groups (P<0.05): the positivity rate of MP was highest in the >6 year-old group; the positivity rates of RSV and Ch were highest in the <1 year-old group; the positivity rates of HPIV and IVB were highest in the 1 to <3 year-old group. RSV, MP, HRV, and HMPV were the main pathogens in children with severe pneumonia, while MP was the primary pathogen in children with lobar pneumonia, and MP, IVB, HMPV, RSV, and HRV were the top 5 pathogens in acute bronchopneumonia.@*CONCLUSIONS@#MP, RSV, IVB, HMPV, and HRV are the main pathogens of CAP in children, and there are certain differences in the positive rates of respiratory pathogens among children of different ages, genders, and seasons.