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1.
Article in Chinese | WPRIM | ID: wpr-928754

ABSTRACT

OBJECTIVE@#To construct a mouse model of Glanzmann's thrombasthenia (GT) with ITGA2B c.2659 C>T (p.Q887X) nonsense mutation by CRISPR/Cas9 technology, and then further explore the expression and function of glycoprotein αIIbβ3 on the surface of platelet membrane.@*METHODS@#The donor oligonucleotide and gRNA vector were designed and synthesized according to the ITGA2B gene sequence. The gRNA and Cas9 mRNA were injected into fertilized eggs with donor oligonucleotide and then sent back to the oviduct of surrogate mouse. Positive F0 mice were confirmed by PCR genotyping and sequence analysis after birth. The F1 generation of heterozygous GT mice were obtained by PCR and sequencing from F0 bred with WT mice, and then homozygous GT mice and WT mice were obtained by mating with each other. The phenotype of the model was then further verified by detecting tail hemorrhage time, saphenous vein bleeding time, platelet aggregation, expression and function of αIIbβ3 on the surface of platelet.@*RESULTS@#The bleeding time of GT mice was significantly longer than that of WT mice (P<0.01). Induced by collagen, thrombin, and adenosine diphosphate (ADP), platelet aggregation in GT mice was significantly inhibited (P<0.01, P<0.01, P<0.05). Flow cytometry analysis showed that the expression of αIIbβ3 on the platelet surface of GT mice decreased significantly compared with WT mice (P<0.01), and binding amounts of activated platelets to fibrinogen were significantly reduced after thrombin stimulation (P<0.01). The spreading area of platelet on fibrinogen in GT mice was significantly smaller than that in WT mice (P<0.05).@*CONCLUSION@#A GT mouse model with ITGA2B c.2659 C>T (p.Q887X) nonsense mutation has been established successfully by CRISPR/Cas9 technology. The aggregation function of platelet in this model is defective, which is consistent with GT performance.


Subject(s)
Animals , CRISPR-Cas Systems , Codon, Nonsense , Disease Models, Animal , Fibrinogen/genetics , Humans , Integrin alpha2/genetics , Mice , Oligonucleotides , Platelet Glycoprotein GPIIb-IIIa Complex/genetics , RNA, Guide , Thrombasthenia/genetics , Thrombin/genetics
2.
Article in Chinese | WPRIM | ID: wpr-940435

ABSTRACT

ObjectiveTo predict the therapeutic target genes and related signaling pathways of Qinghuangsan (QHP) in the treatment of acute myeloid leukemia (AML) by network pharmacology,molecular docking,and further clarify its mechanisms through in vitro cell experiment. MethodThe active components and targets of QHP were retrieved from traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP),traditional Chinese medicine integrated database (TCMID),TargetNet and SwissTargetPrediction databases,and AML-related target genes were obtained by GeneCards and online mendelian inheritance in man (OMIM) databases. After screening the common targets of QHP and AML,the protein-protein interaction (PPI) network of the common targets was constructed with STRING,followed by gene ontology (GO) term and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis based on RStudio software and clusterProfiler,Bioconductor packages. At the same time,Cytoscape software is used to construct the network of "disease-component-target" and "compound-target-pathway". Select the active ingredients of QHP for molecular docking with the top 8 targets in the "compound-target-pathway" network. In vitro cell experiment and Western blot were used to further verify the anti-AML effect of QHP. ResultThe prediction results show that there are 11 main active components of QHP,and 22 common targets of QHP and AML are collected. KEGG pathway analysis results show that phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinase (MAPK) signaling pathways may play a key role in the treatment of AML disease by QHP. "Compound-target-pathway" network analysis showed that the top 8 targets include Akt1,phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA),mitogen-activated protein kinase kinase 1 (MAP2K1),TP53,serine/threonine kinase (RAF1),B cell lymphoma(Bcl)-2,cysteine aspartic acid specific protease(Caspase)-9 and JUN. Molecular docking results showed that 3-indolyl-β-D-glucopyranoside was optimally docked with MAP2K1,isovitexin docked with PIK3CA,and indirubin docked with Bcl-2. Cell experiments show that 3-indolyl-β-D-glucopyranoside,isovitexin and indirubin can effectively inhibit the proliferation of AML cells,regulate the MAPK/PI3K signaling pathway,and inhibit the expression of Bcl-2 protein. ConclusionQHP can treat AML through "multi-component,multi-target,multi-pathway" synergistic treatment,and its mechanism of pharmacology may be related to the regulation of MAPK signaling pathway and PI3K/Akt signaling pathway.

3.
Article in Chinese | WPRIM | ID: wpr-935271

ABSTRACT

The evaluation methods of immune persistence include direct evaluation, indirect evaluation, model prediction, and meta-analysis and so on. Direct evaluation is the gold standard for evaluating the immune persistence of vaccines by quantifying the protective effect of vaccines on the onset and (or) infection of preventable diseases. Indirect evaluation of immune persistence by immunological surrogate indicators is more widely used in practice. In addition, mathematical models and meta-analysis can also be used to evaluate the immune persistence of vaccines. It is of great significance to select the appropriate evaluation method to analyze the immune persistence of the vaccine according to the specific situation.


Subject(s)
Humans , Immunity , Meta-Analysis as Topic , Vaccines/immunology
4.
China Pharmacy ; (12): 1782-1786, 2022.
Article in Chinese | WPRIM | ID: wpr-934965

ABSTRACT

Augmented renal clearance (ARC)refers to the significant enhancement of patients ’renal function ,which is manifested by the significant increase of glomerular filtration rate ,which increases the clearance of drugs ,and the effective blood drug concentration cannot be achieved under the conventional dose. The efficacy of antibiotics is closely related to the concentration. The influence of renal dysfunction on drug metabolism is an important factor that clinicians should consider when determining the dosage. This article reviews the definition ,risk factors ,occurrence mechanism ,evaluation methods of ARC ,as well as its impact on the pharmacokinetics/pharmacodynamics of antibiotics and administration methods. It is found that ARC widely exists in critically ill patients ,and the risk factors include age (≤50 years old ),brain trauma ,sepsis,multiple trauma , etc. When using antibiotics in ARC patients ,the therapeutic effect of drugs can be improved by increasing the dosage ,prolonging the duration of administration and increasing the frequency of administration. However ,in order to prevent adverse reactions caused by high concentration accumulation of drugs ,it is recommended to try to combine treatment drug monitoring.

5.
Acta Pharmaceutica Sinica ; (12): 1816-1824, 2022.
Article in Chinese | WPRIM | ID: wpr-929439

ABSTRACT

This study was designed to obtain recombinant human thioredoxin (rhTXN) by gene cloning and prokaryotic expression, and evaluated its therapeutic effect in the mouse ulcerative colitis (UC) model induced by dextran sulfate sodium (DSS). The human thioredoxin gene TXN was cloned from the cDNA of Jurkat cells. The recombinant expression plasmid pCold TF-rhTXN was constructed by restriction enzyme digestion. After expression in E. coli BL21 (DE3), recombinant human thioredoxin was purified by a nickel column. Intact rhTXN recombinant protein was obtained after removal of the fusion partner-tag by enzyme digestion and the activity of disulfide reductase was detected by the insulin reduction method. The animal experiments in this study were performed in accordance with the ethical guidelines of the Laboratory Animal Welfare Ethical Review Committee of Nanjing University. Experiment ulcerative colitis was induced by providing mice with sterilized drinking water which contained 3% DSS. rhTXN was injected intraperitoneally. The therapeutic effect was studied by weight change, colon length and HE (hematoxylin and eosin) stained sections. In vivo imaging was used to study the targeting of rhTXN to DSS mice. The GSE107499 data set of GEO database was used to screen the hub genes at the lesional sites of UC and study the correlation with TXN. The experimental results showed that rhTXN was successfully expressed and purified with disulfide reductase activity. rhTXN (100 μg·kg-1) had a significant therapeutic effect on maintaining the weight change of mice (P = 0.000 5) and reducing intestinal injury (P < 0.000 1), and had a colon targeting effect on DSS mice. In GSE107499 data set, TXN in inflammatory sites of UC patients was significantly down regulated (P < 0.01) and negatively correlated with hub gene CD40 (P < 0.01) and positively correlated with hub gene fibronectin 1 (FN1) (P < 0.01). In this study, biologically active rhTXN was successfully prepared and proved to have a promising therapeutic effect on the DSS mouse model, and TXN gene was significantly correlated with the UC hub genes CD40 and FN1.

6.
Acta Pharmaceutica Sinica B ; (6): 274-290, 2022.
Article in English | WPRIM | ID: wpr-929293

ABSTRACT

KRAS‒PDEδ interaction is revealed as a promising target for suppressing the function of mutant KRAS. The bottleneck in clinical development of PDEδ inhibitors is the poor antitumor activity of known chemotypes. Here, we identified novel spiro-cyclic PDEδ inhibitors with potent antitumor activity both in vitro and in vivo. In particular, compound 36l (K D = 127 ± 16 nmol/L) effectively bound to PDEδ and interfered with KRAS-PDEδ interaction. It influenced the distribution of KRAS in Mia PaCa-2 cells, downregulated the phosphorylation of t-ERK and t-AKT and promoted apoptosis of the cells. The novel inhibitor 36l exhibited significant in vivo antitumor potency in pancreatic cancer patient-derived xenograft (PDX) models. It represents a promising lead compound for investigating the druggability of KRAS‒PDEδ interaction.

7.
Article in Chinese | WPRIM | ID: wpr-923960

ABSTRACT

Objective To determine the epidemiological and etiological characteristics of hand,foot,and mouth disease (HFMD) in Pujiang County from 2008 through 2020, so as to provide scientific evidence for prevention and control measures. Methods Descriptive epidemiological analysis was used to analyze HFMD cases retrieved in the Chinese Information System for Disease Control and Prevention in Pujiang County during 2008‒2020. Results From 2008 through 2020, a total of 9 393 cases were documented in Pujiang County, with an annual incidence of 182.3 per 100 000, showing a trend of alternating high-incidence and low-incidence years. The seasonal distribution was bimodal, and the incidence peaked in May-July and November-December. The incidence of HFMD in urban areas was significantly higher than that in rural areas, and the incidence was positively correlated with population density. Majority of cases (94.9%) were children under 5 years old, of which boys had higher incidence than girls. The number of documented cases was the highest among preschool children living in families and kindergartens, accounting for 97.3%. Totally, 558 cases were laboratory confirmed in Pujiang County in 2008-2020, of which severe cases were all caused by EV71 infection. Conclusion Enterovirus serotypes in HFMD have continually changed from 2008 through 2020 in Pujiang County. However, severe HFMD remains principally attributable to EV71 infection, suggesting that it is necessary to strengthen the surveillance on the etiology of HFMD. In addition, it warrants further promotion of EV71 vaccination.

8.
Article in Chinese | WPRIM | ID: wpr-923938

ABSTRACT

Objective To determine the epidemiological and etiological characteristics of hand,foot,and mouth disease (HFMD) in Pujiang County from 2008 through 2020, so as to provide scientific evidence for prevention and control measures. Methods Descriptive epidemiological analysis was used to analyze HFMD cases retrieved in the Chinese Information System for Disease Control and Prevention in Pujiang County during 2008‒2020. Results From 2008 through 2020, a total of 9 393 cases were documented in Pujiang County, with an annual incidence of 182.3 per 100 000, showing a trend of alternating high-incidence and low-incidence years. The seasonal distribution was bimodal, and the incidence peaked in May-July and November-December. The incidence of HFMD in urban areas was significantly higher than that in rural areas, and the incidence was positively correlated with population density. Majority of cases (94.9%) were children under 5 years old, of which boys had higher incidence than girls. The number of documented cases was the highest among preschool children living in families and kindergartens, accounting for 97.3%. Totally, 558 cases were laboratory confirmed in Pujiang County in 2008-2020, of which severe cases were all caused by EV71 infection. Conclusion Enterovirus serotypes in HFMD have continually changed from 2008 through 2020 in Pujiang County. However, severe HFMD remains principally attributable to EV71 infection, suggesting that it is necessary to strengthen the surveillance on the etiology of HFMD. In addition, it warrants further promotion of EV71 vaccination.

9.
Article in Chinese | WPRIM | ID: wpr-906354

ABSTRACT

Vitiligo is a common pigmentary disorder characterized by localized or generalized depigmentation of the skin, resulting in milky white or light pink patches with smooth surface but no rashes.Modern medicine believes that it is closely related to immune function, oxidative stress, autoimmune destruction of melanocytes, heredity, and neurochemical factors, but the specific pathogenesis is still unclear.Due to the easy diagnosis but hard management and the high recurrence rate, vitiligo has seriously affected the quality of life and mental health of patients.At present, it is mainly treated with glucocorticoids, immunomodulators, vitamin D3 derivatives, and antioxidants in western medicine, and the resulting short-term outcomes are satisfactory.However, a series of side effects may be caused by the long-term use.Traditional Chinese medicine (TCM) has a long history of dealing with vitiligo.Guided by the rich experience accumulated in daily practice, it exerts the preventive and therapeutic effects against vitiligo via multiple components, multiple targets, and multiple pathways, without inducing obvious adverse reactions, which has made it widely concerned by many doctors and scholars.As the research concerning the prevention and treatment of vitiligo with TCM intensifies, more and more single Chinese medicinals, Chinese medicinal monomers, and compound prescriptions have been proved to play a therapeutic role via multiple mechanisms.After reviewing the articles on the alleviation of vitiligo with TCM published in the past five years and retrieved from the literature databases, this paper summarized the efficacy of TCM in regulating immune dysfunction, improving oxidative stress injury, protecting melanocyte function, adjusting mitochondrial structure and function, and controlling the alteration of intestinal micro-flora and abnormal microRNA (miRNA) expression, so as to clarify the pathogenesis of vitiligo and provide theoretical and scientific basis for the in-depth study and clinical application of TCM in the prevention and treatment of vitiligo.

10.
Chinese Journal of Digestion ; (12): 118-124, 2021.
Article in Chinese | WPRIM | ID: wpr-885739

ABSTRACT

Objective:To screen the common low-frequency mutation sites in primary biliary cholangitis (PBC) by whole exome sequencing (WES), in order to find PBC-related new susceptibility genes.Methods:From January 2000 to December 2017, the clinical data of seven patients with PBC of three PBC families diagnosed at General Hospital of Tianjin Medical University and two healthy controls were collected. The DNA blood samples were extracted and analyzed by WES. SAMtools 1.3 software was used to detect gene single nucleotide polymorphism (SNP) and indel sites, and gene mutation sites were screened from known databases of 1000 Genome, ExAC, ESP6500 and Novo-Zhonghua gene database. Pymol V2.3.2 software was performed to simulate the three-dimensional structure of major histocompatibility complex-Ⅱ (MHC-Ⅱ), and the amino acid position corresponding to the common mutation sites among families were observed.Results:The age of first diagnosis of seven PBC patients was (61.2±10.2) years. The results of serum test of seven patients indicated that alkaline phosphatase (ALP) level was (306.9±242.5) U/L, γ-glutamyltranspeptidase (GGT) level was (121.7±85.9) U/L, alanine aminotransferase (ALT) level was (47.6±33.1) U/L, aspartate aminotransferase (AST) level was (55.7±34.1) U/L and immunoglobulin G level was (14.9±3.1) g/L. The antinuclear antibody were all cytoplasmic granule types and anti-mitochondrial antibody were all positive. Five PBC patients developed intra-abdominal lymphadenopathy; two patients had extrahepatic autoimmune diseases and the pathological results of liver biopsy of two patients both showed interface hepatitis and small bile duct lesions. Eighteen SNPs were common in three PBC families, which were located in the gene of OTOA, OBSCN and human leucocyte antigen- DRB1( HLA- DRB1). rs200988634 located in OTOA gene was a common polymorphic locus among the three families. rs746424683, rs545316651, rs553144914, rs533059830 and rs56087721 located in OBSCN caused the changes of nine amino acids of different location. There were 12 SNP variations located in HLA- DRB1 gene, which leaded to the changes of 12 amino acids of different location, among them rs16822698, rs112796209 and rs11554463 mutation induced G154A, Y152C and Y107X amino acid variation of MHC-Ⅱ beta chain, and Y107X amino acid was located in the groove region of MHC-Ⅱ binding with peptide. Conclusions:WES in PBC families is a good strategy to elucidate the candidate deleterious mutation genes OBSCN and OTOA. HLA- DRB1 which is a susceptible gene of PBC may affect MHC-Ⅱ mediated antigen presentation process by the changing amino acid sequence.

11.
Chinese Journal of Digestion ; (12): 35-42, 2021.
Article in Chinese | WPRIM | ID: wpr-885733

ABSTRACT

Objective:To explore the role of receptor-interaction protein 3 (RIP3) in regulating the infiltration of monocytes/macrophages into the liver in autoimmune hepatitis (AIH).Methods:From January to June in 2018, at Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, 10 AIH patients who underwent liver biopsy were enrolled, and at the same time, 5 age and gender matched individuals with normal liver function and hepatic cyst were selected as control. The infiltration of monocytes/macrophages in the liver tissues was observed by immunofluorescence detection in the patients with AIH and controls. Raw264.7 macrophages were divided into control group, lipopolysaccharide group and lipopolysaccharide+ RIP3 inhibitor GSK872 (GSK872) group. The expression of RIP3, mixed lineage kinase domain like pseudokinase ( MLKL), tumor necrosis factor ( TNF)- α, interleukin ( IL)-6, IL-1 β, nod-like receptor protein 3 ( NLRP3), CC motif chemokine ligand ( CCL)2 and CCL5 at mRNA levels were detected by quantitative polymerase chain reaction (qPCR). Raw264.7 macrophages were also divided into control group, lipopolysaccharide group and lipopolysaccharide + dexamethasone group. The relative expression of TNF- α, NLRP3, RIP3 and MLKL at mRNA level in macrophage were detected by qPCR. Twenty-four 6-week-old female C57BL/6 mice were chosen to establish AIH mice model and were randomly divided into control group, concanavalin A (ConA) group, ConA+ dexamethasone group and ConA+ GSK872 group (6 mice in each group). After the mice were executed, the peripheral blood and liver tissues were collected. The histopathology of mice liver were observed and the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured. The expression of CCL2 and CC motif chemokine receptor 2 ( CCR2) at mRNA level were detected by qPCR. The proportion of macrophages in mice livers were analyzed by flow cytometry. The independent sample t test and one-way analysis of variance were performed for statistical analysis. Results:The percentages of CD68 positive macrophages and MAC387 positive infiltrated mononuclear macrophages in livers of AIH patients were both higher than those of controls ((0.84±0.21)% vs. (0.09±0.03)%, (0.79±0.13)% vs. (0.03±0.01)%), and the differences were statistically significant ( t=3.00 and 4.84; all P<0.05). The expression of RIP3, MLKL, TNF- α, IL-6, IL-1 β, NLRP3, CCL2 and CCL5 at mRNA level of lipopolysaccharide group were all higher than those of control group and lipopolysaccharide+ GSK872 group (1.64±0.16 vs. 1.07±0.07 and 0.63±0.11; 10.45±1.37 vs. 1.10±0.33 and 1.51±0.63; 5.43±0.59 vs. 0.94±0.06 and 2.59±0.45; 204.20±30.73 vs. 1.26 ±0.19 and 111.40±11.62; 20 848.00±362.00 vs. 1.09 ±0.26 and 10 940.00±566.60; 7.47±1.17 vs. 1.09±0.09 and 3.79±0.89; 68.03±5.15 vs. 1.14±0.19 and 14.09±2.62; 5 935.12±96.20 vs. 1.43±0.46 and 673.50±49.10), and the differences were all statistically significant ( t=3.11, 5.21, 6.65, 6.55, 7.57, 3.96, 6.60, 3.06, 8.83, 4.08, 5.46, 2.56, 12.97, 10.16, 25.34 and 14.99; all P<0.05). The expression of TNF- α, NLRP3, RIP3 and MLKL at mRNA level of lipopolysaccharide group were all higher than those of control group and lipopolysaccharide+ dexamethasone group (8.85±1.43 vs. 1.44±0.43 and 3.63±0.63; 6.42±0.86 vs. 0.99±0.12 and 2.07±0.17; 1.72±0.21 vs. 0.93±0.09 and 0.43±0.07; 6.87±0.85 vs. 1.62±0.31 and 1.41±0.29), and the differences were all statistically significant ( t=4.95, 3.33, 6.24, 4.95, 3.04, 5.11, 5.77 and 6.07, all P<0.05). The mice liver of ConA group showed obviously inflammatory cells infiltration and hepatocytes necrosis. The serum ALT and AST levels of ConA group were both higher than those of control group, ConA+ dexamethasone group and ConA+ GSK872 group ((2 569.00±45.44) U/L vs. (49.38±9.07), (103.00±14.07) and (759.30±34.99) U/L; (3 335.00±88.79) U/L vs. (108.50±18.10), (460.00±97.40) and (1 573.85±36.06) U/L), the serum ALT and AST levels of ConA+ dexamethasone group were both lower than those of ConA+ GSK872 group, and the differences were all statistically significant ( t=5.54, 5.42, 3.90, 4.63, 4.16, 3.79, 6.70 and 2.71; all P<0.05). The expression of CCL2 and CCR2 at mRNA levels in mice liver of ConA group were both higher than those of control group, ConA+ dexamethasone group and ConA+ GSK872 group (92.64±10.57 vs. 0.78±0.15, 5.64±1.00 and 9.47±2.06; 5.73±0.39 vs. 0.98±0.22, 2.18±0.22 and 2.98±0.33), and the differences were all statistically significant ( t=7.66, 7.24, 5.87, 8.71, 8.58 and 5.45; all P <0.01). The proportion of CD45 + CD11b + F4/80 + total macrophages and CD45 + CD11b hiF4/80 lo infiltrated macrophages in mice livers of ConA group were both higher than those of control group, ConA+ dexamethasone group and ConA+ GSK872 group (0.86±0.02 vs. 0.73±0.03, 0.68±0.02 and 0.72±0.03; 0.56±0.02 vs. 0.08±0.02, 0.11±0.01 and 0.08±0.01), however the proportion of CD45 + CD11b loF4/80 hi liver macrophages (Kupffer cells) was lower than those that of control group, ConA+ dexamethasone group and ConA+ GSK872 group (0.24±0.03 vs. 0.58±0.04, 0.52±0.07 and 0.56±0.07), and the differences were all statistically significant ( t=4.27, 5.90, 3.89, 18.70, 19.87, 20.52, 7.35, 3.82 and 3.87, all P<0.05). Conclusions:The number of macrophages incread in the livers of AIH patients. RIP3 signaling mediates the migration of monocytes/macrophages infiltration in immune hepatitis, which may be a potential therapeutic target for AIH.

12.
Article in Chinese | WPRIM | ID: wpr-866353

ABSTRACT

Objective:To investigate the clinical significance of quantitative detection of myocardial edema in acute myocardial infarction based on T 2 mapping. Methods:From July 2018 to February 2019, a total of 20 patients (observation group) who underwent cardiac MRI after interventional therapy in the People's Hospital of Wenzhou were enrolled.Another 20 healthy volunteers were selected as the control group.The image data of the observation group were collected, and the image data were post-processed.The T 2 value, edema area and microcirculation obstacle area of the infarcted myocardium and its contralateral normal myocardium were measured and recorded by the image information.The infarcted myocardium and the contralateral normal myocardium were recorded.The T 2 values were compared and the cardiac MRI, cardiac function, serological markers and heart failure related products of the two groups were compared. Results:The patients in the observation group underwent self-comparison between infarcted myocardium and normal myocardium.The T 2 value of the distal infarcted myocardium was (90.14±.51)ms, which was greater than that of the normal myocardium [(60.71±5.15)ms], the difference was statistically significant( t=8.49, P<0.05). The number of myocardial microvascular obstruction (MVO) in the observation group was 17 cases, which in the control group was 0 cases, the difference was statistically significant (χ 2=41.45, P<0.05). The left ventricular end-diastolic volume of the observation group[(88.5±16.2)mL] was higher than that of the control group[(72.4±15.1)mL], and the difference was statistically significant ( t=12.51, P<0.05). The ejection fraction of the observation group was (54.1±11.2)%, which was lower than that of the control group [(71.2±7.9)%], and the difference was statistically significant ( t=18.71, P<0.05). The T 2 value of the observation group was (69.4±6.4)ms, which was higher than that of the control group[(55.2±11.4)ms]( t=11.98, P<0.05). The degree of myocardial delayed imaging (LGE) in the observation group was 13%, which in the control group was 0%, the difference was statistically significant ( Z=27.62, P<0.05). T 2 mapping showed that myocardial infarction sensitivity and positive predictive value were higher, but its specificity was relatively low. Conclusion:Quantitative T 2 mapping has high clinical value in the evaluation of myocardial edema after acute myocardial infarction.T 2 mapping can be used to analyze the extent of lesions in patients with acute myocardial infarction.

13.
Chinese Journal of Endemiology ; (12): 781-785, 2020.
Article in Chinese | WPRIM | ID: wpr-866217

ABSTRACT

Objective:To identify human infection with Brucella suis, analyze its biological and molecular characteristics, and to provide basis for prevention and control of brucellosis. Methods:Brucella suis strains were isolated from the body of the first case of human Brucella suis infection in Jiangsu Province. Serum agglutination test was used for serotyping. The specific gene bcsp-31 of Brucella was detected by PCR. AMOS-PCR was used to identify IS-711. The species and biotypes were identified by multiplex PCR. The wboA gene products were sequenced and phylogenetic tree was constructed. Multilocus sequence analysis (MLSA) was used for molecular typing, and cluster analysis was performed with reference strains. Results:The strain was confirmed to be Brucella suis biotype 3 by serum agglutination test and PCR. After sequencing the wboA gene, cluster analysis of the reference sequence showed that the wboA gene was closest to the biotype 3 strain Brucella suis str. 686 (CP007719). MLSA was typed into ST17(1-6-4-1-5-3-5-2-4). Conclusions:Brucella suis biotype 3 is reported in Jiangsu Province for the first time. The MLSA type is ST17. In the future, the prevention and control of human brucellosis should be carried out. We should actively cooperate with the animal husbandry and veterinary department to increase the quarantine, immunization and other control measures.

14.
Article in Chinese | WPRIM | ID: wpr-873246

ABSTRACT

Objective::To explore the effect and mechanism of Portulacae Herba protecting carbon tetrachloride (CCl4)-induced acute liver injury. Method::Sixty Kunming mice were randomly divided into normal group, model group, silybin group (200 mg·kg-1) and Portulacae Herba high, medium, low (2, 1, 0.5 g·kg-1) dose groups. After continuous intragastric administration for 5 days, mice in each group were intraperitoneally injected with 0.2% CCl4 peanut oil solution to establish acute liver injury model, except normal mice. After 23 hours of modeling, serum and liver tissue were collected. Fully automatic analysis of serum serum liver function indicators in mice. Liver tissues were taken for hematoxylin-eosin staining (HE) staining to observe liver pathological changes. RNA Sequencing (RNA-seq) was used to analyze differential genes and functional enrichment, real-time fluorescence quantification PCR(Real-time PCR) was used to verify the mRNA expression of cytochrome P450 family members(CYP)26A1, CYP2C37, CYP2C44, CYP2C50, CYP2C54. Result::Compared with normal group, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), total bilirubin (TBIL), malondialdehyde (MDA) in model group were significantly increased (P<0.05), and the activities of triglyceride (TG) and superoxide dismutase (SOD) were significantly decreased (P<0.05). Compared with model group, Portulaca Herba significantly reduced ALT, AST, TBIL and MDA levels in mice with acute liver injury (P<0.05), significantly increased SOD activity (P<0.01), and decreased the degree of liver tissue damage in mice. Compared with normal group, the mRNA expressions of CYP2C44, CYP2C50 in mice with acute liver injury were significantly decreased (P<0.05). Compared with model group, the mRNA expressions of CYP26A1, CYP2C37, CYP2C44, CYP2C50 and CYP2C54 were significantly increased in all dose groups of Portulaca Herba (P<0.05, P<0.01). Conclusion::Portulacae Herba has significant protective effects on acute liver injury caused by CCl4, and its mechanism may be related to the regulation of cytochrome P450 related genes.

15.
Chinese Journal of Digestion ; (12): 9-15, 2020.
Article in Chinese | WPRIM | ID: wpr-798915

ABSTRACT

Objective@#To observe and analyze the role of intestinal barrier in the pathognesis of autoimmune hepatitis (AIH), to explain the pathogenesis of AIH and to explore the intestinal based new treatment strategies.@*Methods@#A total of 14 AIH patients from January to December 2017 at Tianjin Medical University General Hospital (six patients without liver cirrhosis, and eight patients with liver cirrhosis) and 10 healthy controls were enrolled. The serum levels of D-lactic acid (D-Lac) and diamine oxidase (DAO) were detected by enzyme-linked immunosorbent assay. Real time fluorescence quantitative polymerase chain reaction was used to detect the relative expression levels of connexin (zonula occluden-1 (ZO-1), occludin), cytokines (interleukin(IL)-2, interferon(IFN)-γ, IL-4, IL-10) and Toll-like receptor 4 (TLR4) in terminal ileal tissues of each group. The relative expression of secretory immunoglobulin A (sIgA) in the terminal ileum was determined by Western blotting. Thirty BALB/c mice were selected and divided into blank control group, dextran sulfate sodium (DSS) group, concanavalin A (ConA) group, DSS+ ConA group, and DSS+ bacterium+ ConA group, with six mice in each group. The relative expression levels of ZO-1, occludin in mouse colonic tissues, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and inflammatory activity degree of liver tissues (Knodell score) of each group were measured. T-test and one-way analysis of variance were performed for statistical analysis.@*Results@#The serum D-Lac and DAO levels of AIH with liver cirrhosis group and AIH without liver cirrhosis group were both higher than those of healthy control group ((1 768.2±147.1) μg/L, (436.2±197.0) μg/L vs. (100.2±10.9) μg/L, and (11.5±2.5) U/L, (5.4±0.9) U/mL vs. (3.5±0.9) U/mL), and the levels of D-Lac and DAO of AIH with liver cirrhosis group were the highest; and the differences were statistically significant (t=5.512, 36.010, 4.088 and 9.443, F=396.958 and 46.640, all P<0.01). The relative expression levels of ZO-1 and occludin in the terminal ileal mucosa of AIH with liver cirrhosis group were lower than those of healthy control group (0.20±0.14 vs. 1.67±0.51, 0.12±0.09 vs. 0.90±0.21), and the relative expression of ZO-1 in AIH without liver cirrhosis group was lower than that in healthy control group (0.99±0.37 vs. 1.67±0.51); and the differences were statistically significant (t=8.641, 7.407 and 2.295, all P<0.05). The relative expression levels of IL-2 and IFN-γ in terminal ileal tissues of AIH with liver cirrhosis group were higher than those of healthy control group (1.11±0.43 vs. 0.24 ±0.16, and 3.50 ± 1.90 vs. 0.32±0.30), however the relative expression of sIgA in terminal ileal tissues was lower than that of healthy control group (0.506±0.024 vs. 1.081±0.102); and the differences were statistically significant (t=4.679, 3.981 and 5.493, all P<0.05). While the relative expression levels of IL-10 in AIH with liver cirrhosis group and AIH without liver cirrhosis group were lower than that in healthy control group (0.30±0.20, 0.42±0.24 vs. 0.84± 0.23), and the relative expression levels of TLR4 in ileum mucosa of the both groups were higher than that of healthy control group (8.74 ±5.13, 6.74 ±3.65 vs. 0.89 ± 0.70); and the differences were statistically significant (t=3.095, 4.816, 3.856 and 3.685, all P<0.05). The relative expression levels of ZO-1 and occludin of DSS+ ConA group were lower than those of ConA group (0.14±0.08 vs. 0.98±0.13, and 0.09±0.02 vs. 0.98±0.16), however serum ALT, AST levels and the Knodell score were all higher than those of ConA group ((5 496.67±618.83) U/L vs. (3 325.00±1 030.06) U/L, (8 825.00±1 165.35) U/L vs. (5 433.33±1 691.14) U/L, and 18.00±2.00 vs. 9.33±3.01); and the differences were statistically significant (t=13.480, 13.520, 4.227, 4.045 and -2.892, all P<0.05). The relative expression levels of ZO-1 and occludin in DSS+ bacterium+ ConA group were higher than those in DSS+ ConA group (0.46±0.08 vs. 0.14±0.08, and 0.53±0.15 vs. 0.09±0.02), while serum ALT and AST levels were lower than those of DSS+ ConA group ((4 343.33±252.16) U/L vs. (5 496.67±618.83) U/L, and (6 123.33±1 086.60) U/L vs. (8 825.00±1 165.35) U/L); and the differences were statistically significant (t=6.928, 7.122, 4.228 and 4.153, all P<0.01).@*Conclusions@#AIH patients have increased intestinal permeability and impaired intestinal barrier which is more serious in patients with liver cirrhosis than in patients without cirrhosis. The intestinal barrier injury can aggravate ConA-induced immune-mediated liver injury. While the protection and repair of intestinal barrier can alleviate immune-mediated liver injury induced by ConA.

16.
Chinese Journal of Digestion ; (12): 105-109, 2020.
Article in Chinese | WPRIM | ID: wpr-871456

ABSTRACT

Objective:To explore the clinical characteristics of liver function of patients with autoimmune liver disease (AILD) complicated with gallbladder stone (GS), so as to guide clinical practice.Methods:From November 2009 to October 2018, at General Hospital of Tianjin Medical University, the clinical data of 386 patients with AILD were retrospectively analyzed. According to the relevant diagnostic criteria, 208 cases of autoimmune hepatitis (AIH), 129 cases of primary biliary cholangitis (PBC) and 49 cases of PBC-AIH overlap syndrome were screened out. The incidence, clinical characteristics and the changes of laboratory indicators including albumin, alkaline phosphatase (ALP) and γ-glutamyl transferase (GGT) of AILD patients complicated with GS were analyzed. Chi-square test, t test and rank sum test were performed for statistical analysis. Results:There was no significant difference in the incidence between AILD, AIH, PBC and PBC-AIH overlap syndrome patients complicated with GS (32.9%, 127/386; 28.8%, 60/208; 36.4%, 47/129 and 40.8%, 20/49; respectively; P>0.05). Gallstones of AILD patients complicated with GS mostly were multiple and small stones with maximum diameter <1 cm (45.7%, 58/127 and 57.7%, 60/104, respectively). The age of initial diagnosis, the proportion of liver cirrhosis at inital diagnosis and the levels of ALP and GGT were higher in AILD patients complicated with GS than those of AILD patients without GS ((60.5±11.5) years vs. (57.6±11.5) years; 53.5%, 68/127 vs. 42.1%, 109/259; 154.00 U/L (89.00 U/L, 257.00 U/L) vs. 125.00 U/L (86.00 U/L, 212.00 U/L); 169.00 U/L (79.00 U/L, 343.00 U/L) vs. 128.60 U/L (48.00 U/L, 284.00 U/L); respectively); however the albumin level was lower than that of AILD patients without GS ((36.46±7.30) g/L vs. (38.34±7.58) g/L), and the differences were statistically significant ( t=-2.361, χ2=4.506, Z=-2.192, -2.443, t=2.322; all P<0.05). The incidence of GS in AILD patients≥60 years old was higher than that AILD patients<60 years old (37.6%, 73/194 vs. 28.1%, 54/192), and the difference was statistically significant ( χ2=3.948, P=0.047). The incidence of GS in AILD patients and AIH patients complicated with liver cirrhosis was higher than that in patients without liver cirrhosis (38.4%, 68/177 vs. 28.2%, 59/209; 35.7%, 35/98 vs. 22.7%, 25/110; respectively), and the differences were statistically significant ( χ2=4.506 and 4.259, P=0.034 and 0.039). Conclusions:AILD patients complicated with GS are common, most are multiple and small stones. When complicated with GS, the initial diagnosis may be delayed and the rate of liver cirrhosis at initial diagnosis may increase. The incidence of GS is high in AILD patients with older age and liver cirrhosis.

17.
Chinese Journal of Digestion ; (12): 9-15, 2020.
Article in Chinese | WPRIM | ID: wpr-871448

ABSTRACT

Objective:To observe and analyze the role of intestinal barrier in the pathognesis of autoimmune hepatitis (AIH), to explain the pathogenesis of AIH and to explore the intestinal based new treatment strategies.Methods:A total of 14 AIH patients from January to December 2017 at Tianjin Medical University General Hospital (six patients without liver cirrhosis, and eight patients with liver cirrhosis) and 10 healthy controls were enrolled. The serum levels of D-lactic acid (D-Lac) and diamine oxidase (DAO) were detected by enzyme-linked immunosorbent assay. Real time fluorescence quantitative polymerase chain reaction was used to detect the relative expression levels of connexin (zonula occluden-1 (ZO-1), occludin), cytokines (interleukin(IL)-2, interferon(IFN)-γ, IL-4, IL-10) and Toll-like receptor 4 (TLR4) in terminal ileal tissues of each group. The relative expression of secretory immunoglobulin A (sIgA) in the terminal ileum was determined by Western blotting. Thirty BALB/c mice were selected and divided into blank control group, dextran sulfate sodium (DSS) group, concanavalin A (ConA) group, DSS+ ConA group, and DSS+ bacterium+ ConA group, with six mice in each group. The relative expression levels of ZO-1, occludin in mouse colonic tissues, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and inflammatory activity degree of liver tissues (Knodell score) of each group were measured. T-test and one-way analysis of variance were performed for statistical analysis. Results:The serum D-Lac and DAO levels of AIH with liver cirrhosis group and AIH without liver cirrhosis group were both higher than those of healthy control group ((1 768.2±147.1) μg/L, (436.2±197.0) μg/L vs. (100.2±10.9) μg/L, and (11.5±2.5) U/L, (5.4±0.9) U/mL vs. (3.5±0.9) U/mL), and the levels of D-Lac and DAO of AIH with liver cirrhosis group were the highest; and the differences were statistically significant ( t=5.512, 36.010, 4.088 and 9.443, F=396.958 and 46.640, all P<0.01). The relative expression levels of ZO-1 and occludin in the terminal ileal mucosa of AIH with liver cirrhosis group were lower than those of healthy control group (0.20±0.14 vs. 1.67±0.51, 0.12±0.09 vs. 0.90±0.21), and the relative expression of ZO-1 in AIH without liver cirrhosis group was lower than that in healthy control group (0.99±0.37 vs. 1.67±0.51); and the differences were statistically significant ( t=8.641, 7.407 and 2.295, all P<0.05). The relative expression levels of IL-2 and IFN-γ in terminal ileal tissues of AIH with liver cirrhosis group were higher than those of healthy control group (1.11±0.43 vs. 0.24 ±0.16, and 3.50 ± 1.90 vs. 0.32±0.30), however the relative expression of sIgA in terminal ileal tissues was lower than that of healthy control group (0.506±0.024 vs. 1.081±0.102); and the differences were statistically significant ( t=4.679, 3.981 and 5.493, all P<0.05). While the relative expression levels of IL-10 in AIH with liver cirrhosis group and AIH without liver cirrhosis group were lower than that in healthy control group (0.30±0.20, 0.42±0.24 vs. 0.84± 0.23), and the relative expression levels of TLR4 in ileum mucosa of the both groups were higher than that of healthy control group (8.74 ±5.13, 6.74 ±3.65 vs. 0.89 ± 0.70); and the differences were statistically significant ( t=3.095, 4.816, 3.856 and 3.685, all P<0.05). The relative expression levels of ZO-1 and occludin of DSS+ ConA group were lower than those of ConA group (0.14±0.08 vs. 0.98±0.13, and 0.09±0.02 vs. 0.98±0.16), however serum ALT, AST levels and the Knodell score were all higher than those of ConA group ((5 496.67±618.83) U/L vs. (3 325.00±1 030.06) U/L, (8 825.00±1 165.35) U/L vs. (5 433.33±1 691.14) U/L, and 18.00±2.00 vs. 9.33±3.01); and the differences were statistically significant ( t=13.480, 13.520, 4.227, 4.045 and -2.892, all P<0.05). The relative expression levels of ZO-1 and occludin in DSS+ bacterium+ ConA group were higher than those in DSS+ ConA group (0.46±0.08 vs. 0.14±0.08, and 0.53±0.15 vs. 0.09±0.02), while serum ALT and AST levels were lower than those of DSS+ ConA group ((4 343.33±252.16) U/L vs. (5 496.67±618.83) U/L, and (6 123.33±1 086.60) U/L vs. (8 825.00±1 165.35) U/L); and the differences were statistically significant ( t=6.928, 7.122, 4.228 and 4.153, all P<0.01). Conclusions:AIH patients have increased intestinal permeability and impaired intestinal barrier which is more serious in patients with liver cirrhosis than in patients without cirrhosis. The intestinal barrier injury can aggravate ConA-induced immune-mediated liver injury. While the protection and repair of intestinal barrier can alleviate immune-mediated liver injury induced by ConA.

18.
Article in Chinese | WPRIM | ID: wpr-870750

ABSTRACT

Objective:To investigate the basic knowledge of chronic obstructive pulmonary disease (COPD) among physicians in primary hospitals (county and township hospitals) in Shanxi province.Methods:A electronic questionnaire survey that included questions on basic knowledge, epidemiology, diagnosis and management of COPD was conducted. The questionnaire was distributed through Wechat communication by convenient sampling among physicians and respiratory specialists in primary hospitals in Shanxi province.Results:A total of 1 162 questionnaires were collected, among which 1 100 were valid (882 from county hospitals and 218 from township hospitals). The results showed that 768 (69.8%) considered that smoking and biomass fuel exposure were the main risk factors of COPD, while 639 (58.1%) thought that COPD patients needed to quit smoking. Only 334 respondents (30.4%) indicated that their COPD knowledge was derived from guidelines; 764 respondents (69.5%) considered pulmonary function tests as the gold standard for diagnosing COPD, but only 407 (37.0%) provided correct answers for the specific criteria of pulmonary function, and only 98 respondents (8.9%) correctly identified the diagnostic criteria for severe COPD. In comparison with the county hospital group, fewer doctors in the township hospitals received their COPD knowledge from guidelines [23.9%(52/218) vs.32.0%(282/882), χ 2=5.450, P<0.05]; more doctors in the township hospitals experienced difficulties in the diagnosis and treatment of COPD, including inadequate spirometers in their hospitals [59.6%(130/218) vs. 45.2% (399/882), χ 2=14.509, P<0.01] and significantly inadequate COPD medications [42.7%(93/218) vs.34.2%(302/882), χ 2=5.385, P<0.05]. Significantly lower proportions of general physicians performed pulmonary function tests for COPD patients (χ 2=12.638, P<0.01) and provided correct answers for the diagnostic criteria for severe COPD [6.6%(46/692) vs. 12.7%(52/408), χ 2=11.760, P<0.01] in comparison with respiratory specialists. Conclusions:Doctors in primary hospitals in Shanxi have an inadequate knowledge of COPD. Strengthening COPD-related education and promoting the use of guidelines among doctors remain important issues for successful management of COPD.

19.
Article in Chinese | WPRIM | ID: wpr-743730

ABSTRACT

Objective To investigate the changes of soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) and omentin-1 in patients with H-type hypertension complicated with acute ischemic stroke, and to analyze the correlation of sLOX-1 and omentin-1 levels with the severity and prognosis of the disease.Methods Totally 136 patients with H-type hypertension complicated with acute ischemic stroke from February2017 to May 2018 were selected as observation group, and 136 non-acute ischemic stroke patients with H-type hypertension in the same period as the control group. The patients of observation group were divided into mild, moderate and severe sub-groups according to NIHSS score, and they were also divided into good prognosis group and poor prognosis group based on modified RANKIN scale (mRS) score. The serum sLOX-1 and omentin-1 levels were detected, and the correlation of sLOX-1 and omentin-1 levels with severity and prognosis of disease was analyzed. Results The serum sLOX-1 level of the observation group was higher, but the serum omentin-1 level lower than that of control group (P < 0.05). With the severity of the disease, the serum sLOX-1 level increased, but the serum omentin-1 level decreased (P < 0.05). The serum sLOX-1 level of good prognosis group was significantly lower, whereas the serum omentin-1 level significantly higher than that of poor prognosis group (P < 0.05). sLOX-1 was positively correlated with NIHSS score and mRS score, while omentin-1 was negatively correlated with NIHSS score and mRS score (P < 0.05). Conclusions The levels of serum sLOX-1 and omentin-1 are closely related to the severity and prognosis of patients with H-type hypertension complicated with acute ischemic stroke, which could be used as markers for evaluating the severity and prognosis of the patients.

20.
Chinese Journal of Digestion ; (12): 244-250, 2019.
Article in Chinese | WPRIM | ID: wpr-746124

ABSTRACT

Objective To provide clues for the study on the mechanism of autoimmune liver disease (AILD) by exploring the existence of specific bacteria in liver tissues of AILD patients.Methods From August 2017 to August 2018,at Department of Gastroenterology arnd Hepatology,Tianjin Medical University General Hospital,a total of 12 patients diagnosed as AILD (four autoimmune hepatitis (AIH),four primary biliary cirrhosis (PBC) and four PBC-AIH overlap syndrome (OS)) and four patients with hepatic cyst (control group) were enrolled and all the patients underwent liver biopsy.16S rRNA gene sequencing was carried out in the obtained aseptic liver tissues.Linear discriminant analysis effect size was used to find out the specific bacteria.Spearman correlation analysis was performed to analyze the correlation between the liver microbiota and the disease.The metabolic function of the 16S rRNA gene sequences was also predicted.Results Bacteria were detected in the liver tissues of all the 16 patients.At the species level,the abundance of Planococcus rifietoensis of AIH group was 0.100%,which was higher than those of other three groups (0),and the difference was statistically significant (linear discriminant analysis (LDA) =3.31,P =0.034).The abundance of Anoxybacillus flavithermus of PBC group was 0.200%,which was higher than those of other three groups (0.100%),and the difference was statistically significant (LDA =3.34,P =0.014).The abundance of Pseudomonas aeruginosa PAO1,Bacillus firmus,Brevibacillus agri,Acinetobacter baumannii,Sphingomonas zeae and Salmonella enterica were significantly negatively correlated with serum level of γ-glutamyl transferase (r=-0.68,-0.68,-0.67,-0.68,-0.68 and-0.66,all P <0.01).Compared with that of the hepatic cyst group,the lipid metabolism of AILD patients decreased.The levels of serum low density lipoprotein and total cholesterol were significantly negatively correlated with the biosynthesis of unsaturated fatty acids (r =-0.55 and-0.65,both P < 0.05).Conclusions There exist specific bacteria in the liver tissues of AIH and PBC groups.The liver microbiota which is closely related with the pathogenesis of AILD might be a potential therapeutic target and diagnostic biomarker.

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