摘要
BACKGROUND:The Yi people have used Sambucus adnata Wall to treat fractures,bruises,arthritis,etc.The author's group found that the active site aqueous extract(SAW-A)and dichloromethane extract(SAW-B)can promote fracture healing by promoting the expression of genes related to osteoblast proliferation,differentiation and maturation,differentiation and maturation.However,the therapeutic effect of methanol extract(SAW-C)at its active site on osteoarthritis is unclear. OBJECTIVE:To investigate the therapeutic effect of Sambucus adnata Wall extract on osteoarthritis,and to identify the effective targets of Sambucus adnata Wall extract in the treatment of osteoarthritis by network pharmacology technology. METHODS:A rat osteoarthritis model was replicated by anterior cruciate ligamentectomy and model rats were then treated with methanol extract of Sambucus adnata Wall by gavage for 21 days.On the 21st day after modeling,the knee joint of rats was detected by X-ray,the width of the knee joint was measured,oxidative stress indexes and inflammatory factors levels in serum and joint lavage fluid were detected,the morphology of the knee joint was observed by hematoxylin-eosin staining,full-thickness cartilage and hyaline cartilage thickness were measured,and the content of articular cartilage proteoglycan was observed by safranin O-fast green staining.The"drug-component-disease-target"network was constructed.Gene ontology enrichment analysis and Kyoto encyclopedia of genes and genomes enrichment analysis of effective targets were performed,and protein-protein interaction network maps were constructed using cytoscape software. RESULTS AND CONCLUSION:Sambucus adnata Wall extract could reduce tumor necrosis factor-α level in joint lavage fluid and serum levels of prostaglandin E2 and malondialdehyde,while increase the level of superoxide dismutase;relieve joint swelling caused by osteoarthritis;improve the histopathological state of articular cartilage,maintain the thickness of full-thickness articular cartilage,hyaline cartilage and the area of bone trabeculae in subchondral bone;and effectively prevent the loss of proteoglycans in articular cartilage and have a chondroprotective effect.Network pharmacological results showed that the methanol extract of Sambucus adnata Wall may have some targets related to inhibition of tumor necrosis factor,AKT1,interleukin-6,MAPK3,and SRC as well as inhibition of over-activation of EGFR signaling pathway and AGE-RAGE signaling pathway.
摘要
BACKGROUND:Previous studies showed that extracts of Sambucus adnata Wall.have the ability to promote the proliferation and differentiation of osteoblasts,fracture healing,anti-inflammatory and antioxidant effects,which can effectively alleviate the development of osteoarthritis.Vascular endothelial growth factor,on the other hand,is a biomarker for the evaluation of osteoarthritis severity. OBJECTIVE:To investigate the effect and mechanism of two extracts of Sambucus adnata Wall.(methanol extract SAW-ME and dichloromethane extract SAW-DCE)on angiogenesis in osteoarthritis. METHODS:(1)Rat models of osteoarthritis were established using anterior cruciate ligament transection and given SAW-ME and SAW-DCE.A sham group was set as a control.Immunohistochemistry and immunofluorescence were used to detect the changes of articular vascular endothelial growth factor A in joint tissue and vascular endothelial growth factor and"H"type blood vessels in serum of osteoarthritis rats.(2)Vascular endothelial cells EA.hy926 were used as the research object and intervened with SAW-ME and SAW-DCE.Cell proliferation was then detected by MTT assay.Vascular endothelial growth factor was used to induce EA.hy926 cells,and the model of angiogenesis was replicated.Cell scratch assay and tube formation assay were performed to study the role and mechanism.(3)EA.hy926 cells were used for transcriptome sequencing to analyze the characteristic changes of cell differential genes and related functions after SAW-DCE intervention. RESULTS AND CONCLUSION:(1)SAW-ME and SAW-DCE downregulated the expression of vascular endothelial growth factor A in the rat knee cartilage and reduced the formation of"H"type vessels in osteoarthritis rats.SAW-ME could significantly decrease the level of vascular endothelial growth factor in serum of osteoarthritis rats(P<0.05).SAW-DCE could also decrease the level of vascular endothelial growth factor in serum of osteoarthritis rats,but there was no significant change.(2)Both SAW-ME and SAW-DCE significantly inhibited vascular endothelial cell migration and tube formation,and downregulated the expression of Ang1 and Tie2 proteins.(3)Transcriptome sequencing analysis found that abnormal angiogenesis in osteoarthritis was related to the PI3K/AKT signaling pathway.(4)To conclude,SAW-ME and SAW-DCE can inhibit angiogenesis in the rat model of osteoarthritis,and the mechanism may be related to the Ang1/Tie2 and PI3K/AKT signaling pathways.
摘要
Organ transplantation has become an effective treatment for multiple end-stage diseases. However, the recipients of organ transplantation need to take immunosuppressive drugs for a long time after operation, which leads to low immune function and relatively high incidence of bacterial, viral and fungal infections. Traditional microbial detection methods, such as pathogen culture, immunological detection and polymerase chain reaction, have been widely applied in infection detection, whereas these methods may cause problems, such as long detection time and presumed pathogens. Metagenomic next-generation sequencing has been widely adopted in infection prevention and control in organ transplantation in recent years due to high detection rate and comprehensive detection of pathogen spectrum. In this article, the application of metagenomic next-generation sequencing in the prevention and control of infection in solid organ transplantation was reviewed, aiming to provide reference for the diagnosis and treatment of transplantation-related infection.
摘要
ObjectiveTo explore the risk of different levels of pre-pregnancy obesity on trimester-specific thyroid dysfunction. MethodsQuestionnaire information， blood samples， and urine samples from a 2017 pregnancy cohort study in Shanghai， China were collected. A total of 2 455 pregnant women were included in the analysis. Pre-pregnancy BMI was calculated based on the height and self-reported pre-pregnancy weight. Serum TSH， total thyroxine （TT4）， free thyroxine （FT4）， total triiodothyronine （TT3）， free triiodothyronine （FT3）， thyroid globulin antibody（TgAb）， and Thyroid peroxidase antibody （TPOAb） were measured using the electrochemiluminescence method. Urine iodine levels were measured using the acid digestion method. Levels of thyroid function indexes of pregnant women with different degrees of obesity during pre-pregnancy were compared， and trimester-specific thyroid dysfunction was evaluated according to the reference range of trimester-specific thyroid hormone established by this cohort. Multivariate logistic regressions analysis was used to assess the correlation between pre-pregnancy obesity and trimester-specific thyroid dysfunction. ResultsAs the degree of obesity increased， maternal levels of FT3 and TT3 gradually increased during pregnancy （P<0.001， P=0.001）， while FT4 levels gradually decreased （P=0.001）. Multivariate logistic regression analysis showed that compared with the normal weight group， pregnant women who were overweight or obesity before pregnancy had a significantly higher risk of hypothyroxinemia （OR=3.85， 95%CI： 2.08‒7.14， P<0.001） and high TT3 （OR=2.78， 95%CI： 1.45‒5.26， P=0.002） during pregnancy. ConclusionPre-pregnancy overweight or obesity can increase the risk of thyroid dysfunction during pregnancy.
摘要
Background Multiple studies have shown a close relationship between changes in gut microbiota composition and obesity, and research results are influenced by factors such as race and geographical location, but there are few studies on children. Objective To analyze the diversity of gut microbiota related to obesity in a population of 2-6 years old, observe the distribution characteristics and species differences of gut microbiota between obese/overweight and normal weight groups, and explore the association betweenobese/overweight and gut microbiota diversity. Methods Fecal samples were collected from 74 children aged 2-6 years in Shanghai, including 18 obese/overweight individuals, 6 males and 12 females (male to female ratio of 1∶2), and 56 normal weight individuals, 18 males and 38 females (male to female ratio is nearly 1∶2). The 16S rDNA was extracted from bacteria in fecal samples, followed by PCR amplification, cDNA construction, and high-throughput sequencing. Naive Bayes algorithm was used to perform taxonomic analysis (phylum, class, order, family, genus, species) and community diversity analysis (Sobs index, Shannon index, Shannoneven index, Coverage index, PD index, and principal co-ordinates analysis) on representative sequences and abundance of amplicon sequence variants (ASV). Wilcoxon rank sum test, P-value multiple test correction, and analysis of similarities were used to test differences between the two groups to obtain information on the distribution characteristics and species differences of intestinal microbiota in children. Results Seventy-four fecal samples were sequenced, and the sequencing results were subjected to quality control and filtering. A total of 4905306 optimized sequences were obtained, resulting in 1860 ASVs. The diversity data analysis of ASVs generated 889 species annotation results at 8 taxonomic levels. The alpha diversity analysis showed that the richness (Sobs index), diversity (Shannon index), evenness (Shannoneven index), and phylogenetic diversity (PD index) of fecal community of the obese/overweight children were increased compared to those of the normal weight children, but there were no statistical differences between the two groups (P>0.05). The beta diversity analysis showed that there was little difference in the composition of microbial species between the two groups, and no significant clustering separation was observed. The results of species composition analysis at phylum, order, family, and genus levels of 74 samples showed a consistent core microbiota structure in the two groups of gut microbiota, but there were differences in microbiota composition. The differences in microbial community composition between the two groups were manifested at the taxonomic levels of order, family, and genus, among which phylum Firmicutes, order Erysipelotrichales, family Erysipelatocyclostridiaceae, genus Erysipelotrichaceae_ UCG-003 and genus Catenibacterium were significantly enriched in the obese/overweight group and contributed significantly to the phenotypic difference of obese/overweight [linear discriminant analysis (LDA)=3.72, P<0.01; LDA=3.29, P<0.05). Phylum Proteobacteria, order Enterobacterales, family Enterobacteriaceae, genus unclassified was significantly enriched in the normal weight group and contributed significantly to the phenotypic difference of normal body weight (LDA=3.93, P<0.05). Conclusion The richness and diversity of gut microbiota in obese/overweight children aged 2-6 years in Shanghai are increased, but there is no difference compared to normal weight children. There is a difference in the composition of gut microbiota between the obese/overweight group and the normal weight group.
摘要
This article presents a review on the effect of family environmental factors on adolescent depression patients， in which the domestic and foreign literature on the family environment of adolescent depression patients are thoroughly reviewed with the emphasis of the relevant concepts， assessment tools， impact effects and potential mechanisms， and the research progress， existing limitations and directions for future research are summarized. Additionally， the awareness of the negative family environment associated with depression derives specific reference values for the early identification and prevention of adolescent depression.
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Objective:To retrieve the relevant guidelines and expert consensus on self-management of patients with high-risk foot diabetes, and analyze the content of high-quality guidelines and expert consensus recommendations, so as to provide a reference for the construction of a guidance program for self-management of patients with high-risk foot diabetes.Methods:Computer-retrieved clinical practice guidelines and expert consensus for self-management of patients with high-risk foot for diabetes from databases, guideline networks, and related professional websites. The search period was from January 1, 2012 to June 5, 2022. The quality of the included literature was evaluated and the evidence was extracted and integrated by 2 researchers. Experts were invited to evaluate the summarized evidence.Results:According to the quality of literature, a total of 12 guidelines (10 at level A and 2 at level B) and 3 expert consensus (expert discussion and decision) were included, and 8 themes were defined as regular follow-up, self-assessment, foot and decompression management, exercise management, nutrition management, indicator management, psychological management, and health education, a total of 28 recommendations. Among them, there were 23 A-level recommendations and 5 B-level recommendations.Conclusions:The quality of the guidelines and expert consensus included in this study is high,the recommended level of the summarized evidence is high. This study provides the reference and basis for the clinical staff to construct and guide the clinical practice of self-management of high-risk diabetic foot patients.
摘要
Objective:To investigate the effect of recombinant lipoproteins of Brucella outer membrane protein 16, 19 (L16 and L19) on the expression of immune regulatory factors in human monocytic leukemia cell line (THP-1 cells). Methods:THP-1 cells activated with phorbol ester (PMA) were used as an in vitro experimental cell model, and a group design was used to co-culture L16, L19 and THP-1 cells (L16 stimulated group, L19 stimulated group), respectively. THP-1 cells activated with PMA were used as the control group. When co-cultured for 4 hours, immunofluorescence staining (IFS) and Western blotting were used to detect whether L16 and L19 entered the cells, respectively; when co-cultured for 12, 24 hours, real-time fluorescent quantitative PCR was used to measure the mRNA expression levels of interferon regulatory factor 1 (IRF-1) and trans activator protein of major histocompatibility complex class Ⅱ (CⅡTA); Western blotting was used to detect the protein expression levels of T cell immunoglobulin mucin-3 (Tim-3) and γ interferon receptor 1 (IFNGR1). Results:When co-cultured for 4 hours, L16 and L19 were observed entering THP-1 cells in the L16 stimulated group and L19 stimulated group, respectively. When co-cultured for 12 hours, the expression level of IRF-1 mRNA in the L16 stimulated group (0.16 ± 0.15) was significantly lower than that in the control group (1.00 ± 0.00, P < 0.05). When co-cultured for 24 hours, the expression level of CⅡTA mRNA in the L16 stimulated group (0.17 ± 0.10) was significantly lower than that in the control group (1.00 ± 0.00, P < 0.05). When co-cultured for 12 and 24 hours, there were no statistically significant differences in the expression levels of IRF-1 and CⅡTA mRNA between the L19 stimulated group and the control group ( P > 0.05). Western blotting results showed that there were statistically significant differences in the expression levels of INFGR1 and Tim-3 protein among the control group, L16 stimulated group, and L19 stimulated group after co-cultured for 12 and 24 hours ( F = 50.92, 6.80, 148.73, 156.57, P < 0.05). Among them, when co-cultured for 12 hours, the expression level of INFGR1 protein in the L16 and L19 stimulated groups were significantly lower than that in the control group, and the L19 stimulated group was higher than the L16 stimulated group ( P < 0.05), and the expression level of Tim-3 protein in the L19 stimulation group was higher than that in the control group ( P < 0.05). When co-cultured for 24 hours, the expression level of INFGR1 protein in the L16 and L19 stimulated groups were lower than that in the control group, and the L19 stimulated group was higher than that in the L16 stimulated group ( P < 0.05); and the expression level of Tim-3 protein in the L16 stimulated group was higher than that in the control group and L19 stimulated group ( P < 0.05). Conclusions:Brucella L16 can downregulate the expression levels of IRF-1 and CⅡTA mRNA in THP-1 cells. Both L16 and L19 can downregulate IFNGR1 and upregulate Tim-3 protein expression levels.
摘要
Objective:To construct a follow-up evaluation index system for "Diagnosis of Brucellosis" (WS 269-2019), and provide a reference basis for the next revision and improvement of the standard.Methods:The evaluation index system for "Diagnosis of Brucellosis" (WS 269-2019) was preliminarily established by consulting relevant references and materials. The experts in the field of diagnosis, treatment, prevention and control of brucellosis were selected, and two rounds of expert consultation were carried out in the form of questionnaires using the Delphi method. The necessity and availability of evaluation indicators were scored, and suggestions for modifying and adding indicators were put forward. Based on this, a standard follow-up evaluation index system was established. At the same time, a judgment matrix was constructed combined with the Saaty scale, and the analytic hierarchy process was used to calculate the weight of each index in the system.Results:After 2 rounds of expert ( n = 10) consultation, a standard follow-up evaluation index system for "Diagnosis of Brucellosis" (WS 269-2019) was constructed with 3 first-level indexes, 8 second-level indexes and 21 third-level indexes. The positive coefficients of experts in 2 rounds of questionnaires were both 100%; the coefficient of authority of experts was 0.82; the Kendall's coefficients of concordance of first-level, second-level and third-level indexes were 0.722, 0.260, and 0.181, respectively, with P < 0.05. Among the first-level indexes, the weight of standard quality evaluation was the highest (0.364), and the weight of standard implementation status was the lowest (0.278); among the second-level indexes, the combined weight of social benefits was the highest (0.186), and the combined weight of advanced nature was the lowest (0.043); among the third-level indexes, the combined weight of timely diagnosis rate was the highest (0.096), and the combined weight of consistency with technical data was the lowest (0.009). Conclusions:The constructed follow-up evaluation index system for "Diagnosis of Brucellosis" (WS 269-2019) is scientific and reliable, which evaluated qualitatively and quantitatively, reduces the defects of a single evaluation, and provides a basis for subsequent revision and improvement of the standard.
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Objective:To analyze the epidemiological characteristics and related indicators of plague in Yulin City, Shaanxi Province, and to evaluate the risk of plague epidemic in the future and formulate scientific and reasonable prevention and control measures.Methods:The plague surveillance data of national (Dingbian County) and provincial (Yuyang District, Jingbian County, Hengshan District, Shenmu City, Fugu County) plague monitoring sites in Yulin City from 2011 to 2021 were collected through the China Disease Prevention and Control Information System Pestis Prevention and Control Management Information System, and the plague epidemic situation among humans and animals, the main host animals and their flea infection were analyzed by descriptive epidemiological methods. The expert consultation method and plague risk assessment tool V1.0 were used to assess the epidemic risk of the plague in Yulin City.Results:There was no human and animal plague epidemic in Yulin City from 2011 to 2021. In national monitoring site, the density of main host animal was 5.79/hm 2, ranging from 3.02/hm 2 to 9.08/hm 2,the dominant species was Mongolian gerbil, accounting for 98.21% (3 402/3 464); the capture rate of wild nocturnal rodents was 1.27% (350/27 600), ranging from 0.21% to 3.83%, the dominant species was Cricetulus barabensis, accounting for 44.86% (157/350); the flea infection rate of the rodent body was 16.91% (768/4 541), with a flea index of 0.40, the dominant flea species was the Nosopsyllus laeviceps kuzenkov, accounting for 66.54% (1 203/1 808). In provincial monitoring site, the density of main host animals was 0.49/hm 2, ranging from 0.31/hm 2 to 0.67/hm 2, the dominant species was Alashan ground squirrel, accounting for 63.61% (194/305); the capture rate of nocturnal rodents in the wild was 1.76% (560/31 795), ranging from 0.89% to 3.93%, the dominant species was Roborovski dwarf hamster, accounting for 26.61% (149/560); the capture rate of domestic rats was 2.37% (397/16 750), ranging from 1.48% to 3.10%, the rodents included Rattus norvegicus (47.36%, 188/397) and house mouse (52.64%, 209/397); the flea infection rate of the rat body was 13.26% (182/1 373), with a flea index of 0.40; the dominant flea species was Ophthalmopsylla jettmari, accounting for 45.23% (251/555). The 5 281 pathogenic culture samples and 2 110 serological test samples were all negative. The Pearson correlation analysis results showed that there was no correlation between rodent density and flea infection rate or flea index at national and provincial monitoring sites ( r = - 0.26, - 0.48, 0.09, 0.12, P > 0.05), while flea infection rate and flea index were positively correlated ( r = 0.67, 0.81, P < 0.05). In 2022, Yulin City, Shaanxi Province was not ruled out the possibility of human plague epidemic, and the risk of plague epidemic among animals was high. Conclusions:From 2011 to 2021, the density of the main host animals at the national and provincial monitoring sites in Yulin City has remained at a low level, and the flea index has increased. There is a risk of plague epidemic in Yulin City, so the monitoring work should be further strengthened, and emergency supplies and capacity reserves should be well prepared.
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Objective:To analyze the pathogens distribution, drug resistance and risk factors of bacterial infection in patients undergoing liver transplantation for liver failure.Methods:The retrospective case-control study was conducted. The clinical data of 88 patients with liver failure who underwent liver transplantation in The First Affiliated Hospital of Xi′an Jiaotong University from July 2020 to June 2023 were collected. There were 57 males and 31 females, aged (44±9)years. Observation indicators:(1) incidence and pathogens distribution of bacterial infection in patients undergoing liver transplantation for liver failure; (2) drug resistance of bacteria; (3) risk factors of bacterial infection in patients undergoing liver transplantation for liver failure. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers and percentages. Univariate analysis was conducted using the chi-square test or Fisher exact probability. Multivariate analysis was conducted using the Logistic regression model. Results:(1) Incidence and pathogens distribution of bacterial infection in patients undergoing liver transplantation for liver failure. Of 88 patients, 40 cases had bacterial infection after liver transplantation, with the incidence as 45.45% and occurrence time as postoperative 18(range, 1-57)days. Of the 40 cases with bacterial infection after liver transplantation, 9 cases had single strain infection and 31 cases had mixed bacterial infection. A total of 135 strains of different pathogenic bacteria were isolated from 40 patients, 106 of which were Gram-negative bacteria, 29 were Gram-positive bacteria. Of the Gram-negative bacteria, the top 4 pathogenic bacteria were 37 strains of Acinetobacter baumannii, 35 strains of Klebsiella pneumoniae, 11 strains of Pseudomonas aeruginosa, 9 strains of Stenotrophomonas maltophilia. Of the Gram-positive bacteria, there were 22 strains of Enterococcus faecium, 3 strains of Staphylococcus aureus, 3 strains of Staphylococcus epidermidis, 1 strain of Staphylococcus haemolyticus. Of the 135 strains of pathogenic bacteria, 64 strains were isolated from respiratory tract, 26 strains were from abdomen, 23 strains were from biliary tract, 16 strains were from blood, 6 strains were from other sites. (2) Drug resistance of bacteria. Of the Gram-negative bacteria, Acinetobacter baumannii had a resistance rate of lower than 30.0% to colistin, tigacyclinei, minocycline, a resistance rate of 30.0%-50.0% to amikacin and tobramycin, a resistance rate of over 70.0% to cefotetan, ceftazidime, cefepime, cefoperazone/sulbactam, piperacillin/tazobactam, meropenem, imipenem, ciprofloxacin, cotrimoxazole, levofloxacin. Klebsiella pneumoniae showed a resistance rate of lower than 30.0% to ceftazidime/avibactam, colistin, tigacyclinei and a resistance rate of more than 70.0% to other tested antibiotics. Pseudomonas aeruginosa showed a resistance rate of more than 50.0% to meropenem, imipenem, levofloxacin and a resistance rate of lower than 50.0% to other tested antibiotics. Stenotrophomonas maltophilia showed a resistance rate of lower than 30.0% to cotrimoxazole, levofloxacin, minocycline. Klebsiella oxytoca showed a resistance rate of more than 50.0% to piperacillin/tazobactam, cefoperazone/sulbactam and a resistance rate of lower than 50.0% to other tested antibiotics. The resistance rate of Escherichia coli to amikacin, tobramycin, ceftazidime/avibactam, colistin, and tigecycline was less than 30.0%, and the resistance rate to other tested antibiotics was more than 50.0%. Of the Gram-positive bacteria, Staphylococcus aureus showed a resistance rate of 0 to tigacyclinei, vancomycin, teicoplanin, linezolid, a resistance rate of lower than 50.0% to gentamicin and ciprofloxacin, and a resistance rate of more than 50.0% to erythromycin, penicillin G, ampicillin, tetracycline, levofloxacin. Staphylococcus showed a resistance rate of more than 50.0% to erythromycin, penicillin G, oxacillin, and a resistance rate of 0 to other tested antibiotics. (3) Risk factors of bacterial infection in patients undergoing liver transplantation for liver failure. Results of multivariate analysis showed that preoperative model for end-stage liver disease score ≥30 was an independent risk factor for bacterial infection in patients undergoing liver transplantation for liver failure ( odds ratio=6.440, 95% confidence interval as 2.155-19.248, P<0.05). Conclusions:The incidence of bacterial infection in patients undergoing liver transplantation for liver failure is high, with the most common sites of respiratory tract and abdomen. The pathogenic bacteria are mainly Gram-negative bacteria, which show an extensive and high drug resistance. Preoperative model for end-stage liver disease score ≥30 was an independent risk factor for bacterial infection in patients undergoing liver transplantation for liver failure.
摘要
Objective:To investigate the pathogenic and epidemiological characteristics of human brucellosis in Shaanxi Province, and to provide a basis for scientific prevention and control of human brucellosis in Shaanxi Province.Methods:The pathogenic culture data of 507 reported cases of human brucellosis reported in Shaanxi Province from 2014 to 2021 were collected from the Shaanxi Provincial Center for Disease Control and Prevention. The epidemiological data of the cases were collected from the Infectious Disease Information Reporting Management System of China Disease Prevention and Control Information System. The data were summarized and analyzed using Excel 2016 software, and visualized using ArcGIS 10.6 software.Results:The 507 cases were concentrated from 2018 to 2021 (322 cases), with a peak incidence period from May to July (255 cases). Cases mainly distributed in Weinan City (129 cases), Yulin City (114 cases) and Yan'an City (97 cases). Farmers were the main occupation (415 cases). The cases were mainly aged 40 - 59 (272 cases). The male to female gender ratio was 3.22 ∶ 1.00 (387 ∶ 120). Totally 95.46% (484/507) of the cases had a history of close contact with cattle or sheep, mainly sheep (480 cases). The clinical symptoms included fever, fatigue, hyperhidrosis, joint and muscle pain, with rare liver, spleen and testicular enlargement. Totally 89.55% (454/507) of the cases were diagnosed during the acute phase. In vitro agglutination test, 1 ∶ 200 positive cases were the most common (139 cases). Totally 214 strains of Brucella were isolated and cultured, and the rate of bacterial production was 42.21%, all of which were Brucella melitensis, of which type 3 accounted for 79.91% (171/214). Conclusion:Human brucellosis cases in Shaanxi Province are mainly infected by contact with sheep, with the main source of infection being Brucella melitensis type 3.
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【Objective】 To investigate our experience in the diagnosis and treatment of acute graft-versus-host disease (aGVHD) after liver transplantation in surgical ICU. 【Methods】 We retrospectively analyzed the general data, clinical manifestation, diagnosis, and treatment strategies of five patients with aGVHD after liver transplantation in The First Affiliated Hospital of Xi’an Jiaotong University from January 2000 to December 2019. 【Results】 The incidence rate of aGVHD was 5/850 (5.88 ‰), and all the five patients were male and aged 40-64 years (mean age 56 years). Diabetes, hepatocellular carcinoma, liver transplantation, transcatheter arterial chemoembolization (TACE), and high concentration of immune agents were the main risk factors associated with the development of aGVHD. The average time from surgery until clinical symptom of aGVHD was 15 to 32 days. In our patients with aGVHD, the most common symptom was fever (5/5), followed by skin rash (5/5), pancytopenia (5/5), diarrhea (3/5), and secondary pulmonary infection (3/5). However, liver functions were not remarkable affected. Diagnostic criteria for aGVHD in our center include acute onset, risk factors, typical clinical manifestation, and histopathology after exclusion of differential diseases. Our treatment strategies include high-dose methylprednisolone, stopping/reducing current immunosuppressive protocol, and antilymphocytic agents as second-line treatment. Empirical antibiotics and antifungal agents play a vital part in infections after transplantation. Hematopoietic cytokine was administered to treat pancytopenia. Patients also received supportive therapy, such as isolation and nutritional support, with the goal of benefiting the entire condition. Despite intensive treatment, two of five patients (40%) with aGVHD died due to sepsis and multiorgan failure. One case (20%) died of intracranial hemorrhage and one case (20%) died of tuberculosis. Only one case (20%) stayed alive after 1-year follow-up without complications. 【Conclusion】 The diagnosis of aGVHD relies on clinical suspicion and is confirmed by skin pathology. The patients with aGVHD had early onset (38.5 ℃), large rash range (>50%), complication of sepsis, and poor response to hematopoietic cytokine therapy indicate poor prognosis. Intensive treatment should be started immediately after aGVHD diagnosis. In conclusion, we strongly suggest an early identification, diagnosis, and vigorous treatment strategy, which is the key to improving the prognosis of aGVHD.
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SGLT2 inhibitors currently have clear benefits in the treatment of heart failure whether combined with diabetes or not. Ventricular remodeling after myocardial infarction leads to the occurrence and development of heart failure, and eventually leads to death. There are relatively few studies on SGLT2 inhibitors in patients with myocardial infarction. The purpose of this article is to review the research progress of SGLT2 inhibitors application before and after myocardial infarction.
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Xanthocillin is a unique natural product with an isonitrile group and shows remarkable antibacterial activity. In this study, the genome of an endophytic fungus Penicillium chrysogenum MT-40 isolated from Huperzia serrata was sequenced, and the gene clusters with the potential to synthesize xanthocillin analogues were mined by local BLAST and various bioinformatics analysis tools. As a result, a biosynthetic gene cluster (named for) responsible for the biosynthesis of xanthocillin analogues was identified by further heterologous expression of the key genes in Aspergillus oryzae NSAR1. Specifically, the ForB catalyzes the synthesis of 2-formamido-3-(4-hydroxyphenyl) acrylic acid, and the ForG catalyzes the dimerization of 2-formamido-3-(4-hydroxyphenyl) acrylic acid to produce the xanthocillin analogue N, N'-(1, 4-bis (4-hydroxyphenyl) buta-1, 3-diene-2, 3-diyl) diformamide. The results reported here provide a reference for further discovery of xanthocillin analogues from fungi.
Subject(s)
Penicillium chrysogenum/genetics , Huperzia/microbiology , Acrylates , Multigene Family摘要
OBJECTIVE To study the nephrotoxicity of the extracts from different parts o f Miao medicine Wikstroemia indica in healthy rats ，and to provide reference for the study of its toxicity mechanism and clinical drug use. METHODS Using 70％ ethanol as solvent ，total ethanol extract of W. indica was extracted with diacolation method. After dispersing the above extract with water，the fractions of corresponding fractions were obtained with petroleum ether ，ethyl acetate and n-butanol，and the rest was the extract of water fraction. SD rats were randomly divided into total ethanol extract group ，petroleum ether fraction group ，ethyl acetate fraction group ，n-butanol fraction group ，water fraction group and blank group ，with 12 rats in each group （half male and half female ）. The rats in the administration groups were given the corresponding dose of drug solution intragastrically （total ethanol extract 317.520 mg/kg，petroleum ether fraction 7.875 mg/kg，ethyl acetate fraction 78.435 mg/kg，n-butanol fraction 53.865 mg/kg and water fraction 76.545 mg/kg），once a day ，for conse- cutive 2 weeks，and then stopped taking drug for 2 weeks； rats in the blank group were given equal volume of 1.0％ . sodium carboxymethyl cellulose solution intragastrically. Duringthe experiment ，the general conditions of rats were observed. The samples of urine （on the 14th and 28th day ），serum and bilateral renal tissues （on the 15th and 29th day ）were taken respectively，the renal index was calculated ，the levels of @qq.com renal function indexes in serum and urine were detected ，and the pathomorphological changes of renal tissues were observed. RESULTS During administration ，compared with blank group ，the rats in the total ethanol extract group and ethyl acetate fraction group showed poisoning behavior and activity characteristics such as mental depression ，decreased activity and diet ，thin stool and decreased body mass. The mental state of the rats in the petroleum ether fraction group ，n-butanol fraction group and water fraction group were slightly worse than that in blank group，and slightly decreased activity and diet as well as thin stool ，and slowly increased body mass were found ；however，there was no significant difference in anal temperature in each group. After 2 weeks of administration ，the renal index in total ethanol extract group ，the serum levels of N-acetylglucosaminidase（NAG），urea nitrogen （BUN）and creatinine （Cr）in total ethanol extract group and ethyl acetate fraction group ，serum level of NAG in n-butanol fraction group and serum level of Cr in water fraction group ，as while as NAG levels in urine of rats in total ethanol extract group and petroleum ether fraction group ，NAG and urinary protein levels in urine of rats in ethyl acetate fraction group were increased significantly （P＜0.05 or P＜0.01）. In the pathomorphological observation ，renal tubules showed different degrees of unclear structure ，cell swelling and a few cell necrosis in the total ethanol extract group ，petroleum ether fraction group and ethyl acetate fraction group ，accompanying by glomerular pyknosis，renal tubular sclerosis and inflammatory cell infiltration ，compared with blank group. After drug withdrawal ，the mental state of rats in the administration groups were significantly improved ，the amount of activity and diet increased ，and the stool tended to be normal. Two weeks after drug withdrawal and recovery ，the levels of above indexes in serum and urine of rats in administration groups returned to be close to that in blank group （P＞0.05）；the glomerular structure of rats in each administration group gradually recovered clearly ，and cell swelling and inflammatory cell infiltration were rare in total ethanol extract group ， petroleum ether fraction group and ethyl acetate fraction group. CONCLUSIONS The total ethanol extract ，petroleum ether fraction and ethyl acetate fraction of Miao medicine W. indica have certain nephrotoxicity and reversibility. The toxic component may
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Self-assembling carrier-free nanodrugs are attractive agents because they accumulate at tumor by an enhanced permeability and retention (EPR) effect without introduction of inactive substances, and some nanodrugs can alter the immune environment. We synthesized a peptidyl arginine deiminase 4 (PAD4) molecular inhibitor, ZD-E-1M. It could self-assembled into nanodrug ZD-E-1. Using confocal laser scanning microscopy, we observed its cellular colocalization, PAD4 activity and neutrophil extracellular traps (NETs) formation. The populations of immune cells and expression of immune-related proteins were determined by single-cell mass cytometry. ZD-E-1 formed nanoflowers in an acidic environment, whereas it formed nanospheres at pH 7.4. Accumulation of ZD-E-1 at tumor was pH-responsive because of its pH-dependent differences in the size and shape. It could enter the nucleus and bind to PAD4 to prolong the intracellular retention time. In mice, ZD-E-1 inhibited tumor growth and metastasis by inhibiting PAD4 activity and NETs formation. Besides, ZD-E-1 could regulate the ratio of immune cells in LLC tumor-bearing mice. Immunosuppressive proteins like LAG3 were suppressed, while IFN-γ and TNF-α as stimulators of tumor immune response were upregulated. Overall, ZD-E-1 is a self-assembling carrier-free nanodrug that responds to pH, inhibits PAD4 activity, blocks neutrophil extracellular traps formation, and improves the tumor immune microenvironment.
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Objective:To explore the motivation of the formation of the breastfeeding mission and education behavior of nurses in NICU, analyze the deep reasons, and construct the motivation and path theoretical model of the formation of the breastfeeding mission and education behavior of nurses in NICU.Methods:Through semi-structured interviews, the qualitative research method of grounded theory was used to study 20 nurses in the Second Affiliated Hospital, University of South China from July to September 2020, to construct the motivation and path theoretical model of the formation of the breastfeeding mission and education behavior of nurses in NICU.Results:The research identified five main categories: attitude factor, ability factor, behavior factor, internalization and externalization. Under the influence of three dimensions of attitude level, ability level and behavior level and their cross-layer interaction effects, the NICU nurses were driven to form stable breastfeeding mission and education behaviors through internalization and externalization.Conclusions:Based on the evolutionary context of "multi-dimensional factors and their interaction drivers-internalization-externalization", the relationship between attitude factors, ability factors, behavioral factors, internalization, and externalization are clarified. It provides a theoretical reference basis for managers in managing the breastfeeding propaganda and education of nurses in the NICU, and enriches the theoretical framework of breastfeeding behavior in the NICU.
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Objective:To investigate the role of integrin-linked kinase (ILK)-small interfering RNA (siRNA)-adeno-associated virus (AAV) in scar formation after glaucoma filtering surgery in rat eyes.Methods:Forty-eight Sprague Dawley rats of SPF grade, aged 8 to 9 weeks old, were selected and divided into blank control group, ILK-siRNA-AAV group, NC-siRNA-AAV group and mitomycin C (MMC) group by random number table method, with 12 rats in each group.Left eyes of the rats were taken as experimental eyes, and no intervention was administered to fellow eyes.The bulbar conjunctival filtering bleb after glaucoma filtration surgery in rats was established by anterior chamber drainage tube implantation.One day after operation, phosphate buffer solution, ILK-siRNA-AAV, and NC-siRNA-AAV were injected into the filtering bleb of blank control group, ILK-siRNA-AAV group and NC-siRNA-AAV group, 5 μl each group, respectively.Cotton tablets containing 0.4 mg/ml MMC were placed under conjunctival flap for 5 minutes during operation in MMC group.Intraocular pressure (IOP) was measured with a handheld tonometer before surgery and at 1, 2, 3, 7, 14, 21, 28 days after surgery.Formation of filtering blebs in rats was observed with a surgical microscope at 1, 2, 3, 7, 14, 21, 28 days after operation, and the bleb survival time was calculated by Kaplan-Meier survival analysis.The mRNA and protein expression levels of ILK in conjunctival and subconjunctival tissues at the surgical sites were detected by reverse transcription PCR and Western blot, respectively, on the 28th day after operation.Silencing of ILK gene was identified.Effect of ILK gene silencing on the morphology of drainage pathway was observed by hematoxylin-eosin staining.Effect of ILK gene silencing on collagen fiber deposition in the bulbar conjunctiva at filtration area was examined by Masson staining, and the percentage of positive area of collagen fiber staining in the total tissue visual field was calculated.The use and care of the animals complied with the ARVO Statement.This research protocol was approved by an Ethics Committee of Xi'an Jiaotong University (No.2013-772). Results:There were statistically significant differences in IOP at different time points between before and after surgery among four groups ( Fgroup=76.84, P<0.001; Ftime=114.49, P<0.001). The IOP of ILK-siRNA-AAV group on the 1st, 7th, 14th and 28th day after operation and the IOP of MMC group on the 2nd, 3rd, 7th, 14th and 28th day after operation were lower than those of blank control group, and the differences were statistically significant (all at P<0.05). The IOP of ILK-siRNA-AAV group was lower on 7th, 14th, 21st and 28th day after operation than those of NC-siRNA-AAV group, with statistically significant differences (all at P<0.05). The bleb survival time of blank control group, NC-siRNA-AAV group, ILK-siRNA-AAV group and MMC group was (3.50±1.51), (5.00±3.41), (31.50±3.15) and (31.33±2.46) days, respectively, with a significant difference among them ( F=395.83, P<0.05). The bleb survival time of ILK-siRNA-AAV group and MMC group was higher than that of blank control group and NC-siRNA-AAV group, and the differences were statistically significant (all at P<0.05). There were statistically significant differences in the relative expression levels of ILK mRNA and protein among four groups ( F=222.32, 752.69; both at P<0.05), and the relative expression levels of ILK mRNA and protein were significantly lower in ILK-siRNA-AAV group than blank control group and NC-siRNA-AAV group, and the differences were statistically significant (all at P<0.05). Proliferative fibrous connective tissue and a large number of cells at surgical sites were found in blank control group and NC-siRNA-AAV group, and the fibroblasts were of a high density and grew in clumps.In ILK-siRNA-AAV group, the bulbar conjunctiva was thin, and the arrangement of fibrous connective tissue was loose, and a few proliferative fibroblasts were found.In MMC group, the conjunctival fibrous layer was loose and thin, forming cavities, and scarce cells were found.There was statistically significant difference in the percentage of collagen fiber positive staining area among four groups ( F=741.66, P<0.05). The positive staining percentage of ILK-siRNA-AAV group and MMC group was significantly lower than that of blank control group, among which there was lower positive staining percentage in ILK-siRNA-AAV group than NC-siRNA-AAV group, and the differences were statistically significant (all at P<0.05). Conclusions:Silencing of ILK can inhibit the scar formation after glaucoma filtering surgery and maintain low IOP in rats.
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Objective:To understand the changes of brucellosis prevention and control knowledge awareness among breeders in Chunhua County, Xianyang City, Shaanxi Province before and after the publicity intervention.Methods:A multi-stage cluster sampling method was adopted to select 10 townships with more reported cases of human brucellosis in Chunhua County from January 2019 to June 2020, and each township was given priority to select the administrative village with the largest number of reported cases for investigation. At least 20 breeders aged 20 years old and over in each administrative village were selected, and if the number was insufficient, supplementary surveys would be conducted in other administrative villages with the larger number of breeders in the township. Questionnaire survey was conducted on all subjects, including general demographic characteristics, brucellosis prevention and control knowledge and related protective behaviors. After the baseline investigation, 6 months of brucellosis prevention and control knowledge publicity was carried out in the administrative villages included in the investigation, and the awareness rate of brucellosis prevention and control knowledge before and after the publicity intervention was compared to evaluate the effect of publicity intervention.Results:After the publicity intervention, a total of 240 breeders were investigated, and 176 people were aware of brucellosis prevention and control knowledge, with an overall awareness rate of 73.33% (176/240), which was significantly higher than that before the publicity intervention (57.50%, 115/200), and the difference was statistically significant (χ 2 = 12.21, P = 0.005). After the publicity intervention, the awareness rates of breeders on "can cattle and sheep transmit diseases to humans" and "do you know that cattle and sheep can only be purchased after passing the quarantine inspection" were relatively high, they were 95.83% (230/240) and 95.00% (228/240), respectively, and the differences were statistically significant (χ 2 = 50.04, 112.64, P < 0.001) compared with that before the publicity intervention [71.50% (143/200) and 51.00% (102/200)]. The awareness rate of breeders on "how brucellosis is transmitted from livestock to humans" was the lowest, it was 53.33% (128/240), which was not significantly different (χ 2 = 0.82, P = 0.370) from that before the publicity intervention (49.00%, 98/200). Conclusions:After the publicity intervention, the overall awareness rate of brucellosis prevention and control knowledge of breeders in Chunhua County has improved, but the awareness rate of some individual issues is still low. It is suggested to strengthen the pertinence of publicity and education.