The up-regulation mechanism of membrane type I matrix metalloproteinase (MT1-MMP) in macrophages stimulated by silica in vitro and the contribution of early growth response 1 (Egr-1) transcription factor in the gene expression pathway were investigated. Macrophages stimulated by silica were treated with Egr-1 antibody or Egr-1 decoy oligodeoxynucleotides (ODN). The levels of MT1-MMP proteins were determined by Western blot and the expression of MT1-MMP mRNAs was detected by RT-PCR. The results showed as compared with control macrophages, silica-stimulated group showed up-regulated gene expression of MT1-MMP via Egr-1 (P<0.01). Compared with silica-stimulated macrophages untreated with antibody, the cells treated with 5 microg/mL Egr-1 antibody were associated with reduced expression of MT1-MMP protein (P<0.01) and mRNA (P<0.01). Compared with silica-stimulated untransfected group, the Egr-1 "decoy" ODN group was associated with reduction in the expression of MT1-MMP protein and mRNA (P<0.01). It was concluded gene expression of MT1-MMP which may play a critical role in silicosis was up-regulated by silica in macrophages. Egr-1 participated in the expression of MT1-MMP and positively regulated the expression. Both Egr-1 antibody and Egr-1 decoy ODN suppressed the expression of MT1-MMP through the Egr-1 pathway and may become a potential therapeutic tool in the management of silicosis in the future.

Background The main cause of X linked juvenile retinoschisis is mutation of RS1 gene.The phenotype of X linked juvenile retinoschisis is associated with the mutation types of RS1 gene.However,the relationship of genotype and phenotype of X linked juvenile retinoschisis is unclear.Objective The present study was to survey the clinical phenotype of X-linked juvenile retinoschisis in twelve Chinese families with eleven different mutations in the XLRS1 gene. Methods Complete ophthalmic examinations with slit lamp biomicroscopy,fundus examination and Dhotography were carried out in 28 affected males.Ganzfeld electroretinography (ERG),fundus fluorescein angiography,A and B-scan standardized echography and optical coherence tomography(OCT)were also performed in some patients.The coding regions of the XLRS1 gene that encodes retinoschisin were amplified by polymerase chain reaction(PCR)and analyzed by the single strand conformation polymorphism(SSCP)assay.The RS1 gene mutations were determined by direct sequencing in an automated sequencer.Written informed consent wasobtained prior to the survey. Results The 28 affected males showed a typical foveal schisis with or without peripheral retinoschisis.The typical response to white single flash ERG was seen with a reduction of the b-wave amplitude and a relative preservation of the a-wave amplitude.causing a reduced b/a ratio in the male patients.A total of eleven different XLRS1 mutations in 12 families were identified,four of these mutations,including one frameshift mutaion(22 del T)of exon 1,Asp145His,Arg156Gly and Trp163X mutations of exon 5,were first described in this survey.One non-disease-related polymorphism(NSP),or the 576C to T(Pro192Pro)change of exon 6 was also newly reported herein.In the families with a frameshift(22 del T)mutation of exon 1,a splice donor site mutation(IVS1+2T

OBJECTIVETo evaluate digital rectal examination (DRE) , transrectal ultrasonography (TRUS) , free/total (f-PSA/ t-PSA) prostate-specific antigen (PSA), and PSA density (PSAD) in the diagnosis of prostate cancer (PCa) in patients with PSA < or = 4.0 microg/L.

METHODSBetween April 1996 and December 2012, a total of 343 subjects, aged 30 -91 years, with PSA < or =4.0 microg/L and abnormal findings on DRE or TRUS underwent prostatic biopsy. Based on the levels of PSA, the subjects were divided into four groups: 0 -1.0, 1.1 -2. 0, 2.1 -3. 0, and 3.1 -4.0 microg/L. The diagnostic values of DRE, TRUS, f-PSA/t-PSA, and PSAD were assessed in those with different PSA levels. According to the age, the subjects were again divided into five groups: C49 yr, 50 -59 yr, 60 -69 yr, 70 -79 yr, and > 80 yr. The rates of PCa detection in relation to PSA levels were estimated in different age groups.

RESULTSOf the 343 subjects, 65 (19.0% ) were diagnosed with PCa, with detection rates of 16.28% (21/129) , 17. 17% (17/99), 21.82% (12/55), and 25.00% (15/60) in those with the PSA levels of 0 -1.0, 1.1 -2.0, 2.1 -3.0, and 3.1 -4.0 microg/L, respectively. There were statistically significant differences in f-PSA/t-PSA between the PCa patients and non-PCa subjects with the PSA level > 2.0 microg/L (P <0.05) , but not with the PSA level < or =2.0 microg/L (P > 0.05) , nor did PSAD show any significant difference between the PCa and non-PCa groups ([0.09+/-0. 16] versus [0. 06 +/- 0. 07] micro/L/ml, P > 0. 05). The rate of cancer detection rose -with the elevation of the PSA level, but had no statistically significant difference among different age groups (P >0.05).

CONCLUSIONPSA 2.1 -4.0 microg/L with abnormal DRE and TRUS findings should be considered as a warning signal, which requires regular follow-up and PSA detection. With f-PSA/t-PSA <0. 15 with or without abnormal DRE and TRUS findings, routine prostate biopsy should be performed. PCa diagnosis cannot be effectively established by DRE, TRUS, f-PSA/t-PSA, and PSAD in those with PSA < or = 2.0 microg/L.

Adult ; Aged ; Aged, 80 and over ; Biopsy ; Humans ; Male ; Middle Aged ; Prostate ; pathology ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; diagnosis ; pathology

Objective To explore expression of plexinA1 and Ki-67 in tissue of human brain glioma cells and their clinical significance.Methods 43 specimens from patients with brain glioma were collected.Immunohistochemical (IHC) staining was used for detecting the expression of tissue plexinA1 and Ki-67 in human glioma cells of 43 cases of patients with brain glioma.The positive expression rate of plexinA1 and Ki-67 among the different pathological grade tissues and their clinical significance were analyzed.So did correlation studies about plexinA1 and Ki-67.Results The positive expression rates of plexinA1 in Ⅰ-Ⅱ grade group (18 cases) and Ⅲ-Ⅳ grade group (25 cases) were 22.22 ％ (4/18) and 72.00 ％ (18/25) (P ＜ 0.05).The positive expression rates of Ki-67 in Ⅰ-Ⅱ grade group and Ⅲ-Ⅳ grade group were 16.67 ％ (3/18) and 56.00 ％ (14/25),respectively (P ＜ 0.05).PlxinA1 and Ki-67 expression in the tissue of human brain glioma were positively correlated (r =0.997,P ＜ 0.05).Conclusions The positive expression rate of plexinA1 is higher in high malignancy human glioma group than that in low malignancy group which has an important reference value in the estimation of prognosis for human glioma.PlexinA1 and Ki-67 maybe synergism in occurrence and development of glioma.

Objective To establish human choriocarcinoma JeG-3 cell line resistant to floxuridine (FUDR)and describe the characteristics of this FUDR-resistant subline.The thymidylate synthase (TS) expression level in FUDR-resistant subline was also discussed.Methods The FUDR-resistant sub-line JeG-3/FUDRA was established by intermitted exposure to grads increased FUDR.Reversed microscope was used to observe the morphological changes in FUDR-resistant sub-line.Population doubling time was calculated and compared based on the growth curve of these two cell lines,cell cycles and chromosomal ploidy were assayed with flow cytometry methods.The chemo-luminescence assay was used to detect the hormone secretion by two kinds of cell lines.The resistant index (RI) was measured by cell counting kit-8 (CCK-8)assay.Quantitative RT-PCR was used to detect the mRNA expression level of TS and we also detected the TS mRNA expression level in different doses exposed subline.Results The RI of JeG-3/FUDRA was 31.62.Compared with the JeG-3 cell,the FUDR-resistant cell line had gross changes in morphological,cell growth,cell cycles and chromosomal numbers.The ability of human chorionic gonadotrop(hCG) and progesterone secretion was lower in JeG-3/FUDRA subline.The trend of TS mRNA expression was:while exposed to low concentration of FUDR,the TS mRNA expression level was downregulated,then followed the increasing dose of the drug,the expression level of TS mRNA ascended gradually.When the terminal concentration was reached,the expression level of TS mRNA in JeG-3/FUDRA subline was higher than that of JeG-3 cell line (P＜0.05).Conclusions We established the FUDR-resistant subline of JeG-3 successfully.The TS mRNA expression level is stage-related to the different concentration and different phase in FUDR exposure.Our data suggested that TS mRNA expression level may not be used as a biomarker to predict the chemosensitivity in FUDR-based chemotherapy.

Objective:To evaluate the efficacy and safety of low molecular weight heparin and unfarction heparin in patients with coronary heart disease during percutaneous coronary intervention by investigating the MACE beteewn the percutaneous coronary intervention procedure and post percutaneous coronary intervention 72 hours.Methods:200 patients with coronary heart disease who accepted percutaneous coronary intervention were investigated in this study.According to the anticoagulants,these patients were divided into LMWH subgroup(117 cases) and UFH subgroup(83 cases).According to conventional method,the MACE what happened during percutaneous coronary intervention procedure and post percutaneous coronary intervention 72 hours come from each group of patients was investigated and these statistics were analysised so that evaluate the efficacy and safety of low molecular weight heparin and unfarction heparin.Results:(1) There were no statistical significance in baseline characteristics between the each group (P＞0.05).(2) There were statistical significance in the incidence of TIMI flow slows between the each group (P＜0.05),low molecular weight heparin is superior to unfarction heparin in terms of efficacy.(3)There were no statistical significance in death between the each group (P＞0.05),but there were statistical significance in bleeding / hematoma complications,and other (pericardial tamponade,chest pain,cardiogenic shock,cardiac rapture,ventricular septal perforation,ventricular tachycardia,ventricular fibrillation,cardiac arrest,Aspen attack,stent thrombosis and so on) between the each group (P＜0.05),low molecular weight heparin less adverse reactions,higher safety.Conclusion:Low molecular weight heparin in the percutaneous coronary intervention effect is more significant,and less than UFH adverse reactions and high safety,more suitable for percutaneous coronary intervention anticoagulant therapy.

Objective To study the relationship between the positive expression of human leukocyte antigen B27 (HLA-B27) in different age groups and genders in Uygur and Han nationality in Xinjiang,and explore the clinical value of HLA-B27 in different ethnic groups.Methods From January 2013 to November 2016,1 416 cases of Uygur and Han patients with positive expression of HLA-B27 were detected by flow cytometry.There were 369 cases of Uygur and 1 047 cases of Han.Results Independent samples t-test showed that the positive expression of HLA-B27 in Uygur and Han population was statistically significant (165.22±8.262 vs 163.99±8.113,t=2.479,P=0.013).In male,there was a significant difference in the positive expression of HLA-B27 between Uygur and Han population (165.40 ± 8.237 vs 163.99 ± 8.164,t =2.187,P =0.029).In the age of 41～60 years old and ＞60 years old,the positive expression of HLA-B27 in Uygur was higher than that in Han nationality (166.18 ± 7.650 vs 164.53 ± 8.018,t =2.215,P =0.027;171.63 ± 8.134 vs 167.40 ± 9.469,t =2.126,P=0.035).There was no significant difference in the positive expression of HLA-B27 between Uygur and Han nationality in women,as well as in the age of 20 years and 21～40 years (t=-0.029～1.257,all P＞0.05).Conclusion The investigation showed that the positive expression of HLA-B27 in Uygur was higher than that in Han nationality.The content of HLA-B27 positive expression has racial difference.

Objective:To investigate the clinical and neuroimaging features of atypical teratoid/rhabdoid tumors (AT/RT) of the central nervous system and the survival prognosis in different locations.Methods:The clinical data of 27 patients with AT/RT confirmed by biopsy or postoperative pathology in Sanbo Brain Hospital of Capital Medical University from October 2012 to September 2020 were collected, including 17 males and 10 females, aged (7.6±10.0) years, ranging from 0.2 to 39.0 years old.The clinical features and the results of the first preoperative imaging examination were retrospectively analyzed.The patients were divided into supratentorial, infratentorial and trans supratentorial and infratentorial groups according to the location.The survival time of the three groups was compared by Kaplan-Meier survival curve.Results:All patients presented with headache, including 12 cases with vomiting.There were 12 cases of supratentorial, 10 cases of infratentorial and 5 cases of supratentorial and infratentorial.There were 20 cases of cystic degeneration, 7 cases of calcification, 6 cases of hemorrhage and 13 cases of peritumoral edema.The median survival time of patients with infratentorial AT/RT was longer than that of patients with supratentorial and transtentorial AT/RT (χ 2=7.353, P=0.025). Conclusion:Central nervous system AT/RT is easy to occur in young children, and the survival time of AT/RT patients is longer.

In this study, we explored the mechanism of Huganning tablet (HGNP) in the treatment of nonalcoholic fatty liver disease (NAFLD) based on network pharmacology and computer-aided drug design. Firstly, the potential ingredients and targets of HGNP were identified from TCMSP database, Swiss Target Prediction database, Chinese pharmacopoeia (2015) and literatures, and then the targets of HGNP intersected with NAFLD disease targets that obtained in GeneCards database to acquired potential targets. The bioconductor bioinformatics package of R software was used for gene ontology (GO) enrichment and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. The network of “potential ingredient-key target-pathway” was formed in Cytoscape software to study the interactions between potential ingredients of HGNP, key targets, pathways and NAFLD. Based on the results of network pharmacology, the molecular docking analysis of the key targets and potential active ingredients in HGNP tablets with top degree in the network was conducted using Discovery Studio 2020 software, followed by molecular dynamics simulations, binding free energy calculation, drug-likeness properties analysis and ADMET (absorption, distribution, metabolism, excretion and toxicity) properties prediction. In vitro, HepG2 cells were used to establish steatosis model, and the effects of five key compounds on hepatocyte steatosis were analyzed by oil red O staining and triglyceride (TG) content determination. The results showed that 141 ingredients and 151 potential targets were obtained. A total of 2 526 items and 151 pathways were identified by GO and KEGG enrichment analysis. The molecular docking suggested that five components, isorhamnetin, salvianolic acid B, emodin, resveratrol and rhein, exhibited strong binding ability with key targets [retinoic acid receptor RXR-alpha (RXRA), tumor necrosis factor (TNF), glycogen synthase kinase-3 beta (GSK3B), serine/threonine-protein kinase 1 (AKT1)]. It was further verified that isorhamnetin and salvianolic acid B bind to key targets with good structural stability and binding affinity based on molecular dynamics simulations and binding free energy calculations. The drug-likeness properties, pharmacokinetic properties and toxicity of five key compounds were more comprehensively analyzed through drug-likeness properties analysis and ADMET properties prediction. In vitro, all five compounds, isorhamnetin, salvianolic acid B, emodin, resveratrol, and rhein, improved hepatocyte steatosis of HepG2 cells, confirming the reliability of the present study. In conclusion, based on network pharmacology, computer-aided drug design and in vitro validation, this study investigated the mechanism of HGNP for the treatment of NAFLD at multiple levels and provided a basis for its clinical application.

Antigens, CD34 ; metabolism ; Carcinoma, Signet Ring Cell ; genetics ; metabolism ; pathology ; surgery ; Codon ; Diagnosis, Differential ; Exons ; Female ; Follow-Up Studies ; Gastrectomy ; methods ; Gastrointestinal Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Gastrointestinal Stromal Tumors ; genetics ; metabolism ; pathology ; surgery ; Humans ; Melanoma ; metabolism ; pathology ; Middle Aged ; Neurilemmoma ; metabolism ; pathology ; Point Mutation ; Proto-Oncogene Proteins c-kit ; metabolism ; Receptor, Platelet-Derived Growth Factor alpha ; genetics ; metabolism