A 33-year-old male patient complained of presenting goiter on the low back area for 2 months. Pathological examinations of resected goiter suggested non-Hodgkin lymphoma and showed that T cells, immunoblasts, and hemogram were roughly normal, and 2% sarcoma cells could be found in bone marrow. Stage Ⅳ T-cell non-Hodgkin's lymphoma was diagnosed. Following 4 months of chemotherapy using CHOP protocol (cyclophosphamide, adriamycin, vincristine, and prednisone included), the patient underwent bone marrow activation and autologous peripheral blood stem cell transplantation in combination with recombinant interleukin-2 application in April 1998. The preprocessing was performed under MACC protocol (L-sarcolysinum, cytarabine, cyclophosphamide, and Iomustine included). Ten days after autologous stem cell transplantation, neutrophil concentration was > 0.5×109/L and sixteen days after transplantation, blood platelet concentration was > 50×109/L. Six days after transplantation, the patient exhibited fever, and E. Coli infection was confirmed through blood culture. After antibiotic treatment, body temperature recovered to normal, and fever disappeared. The patient had been followed-up for 10 years and 10 months. During the follow-up period, he lived a normal life and work.

Objective To investigate the total number, reasons, and distributing characteristics of vagrant psychosis patients in Xi'an. Methods The colony random sample in 4 objective research units from 2005 to 2010 in Xi'an, Shaanxi were included. Databank was set up according to the total number of vagrant psychosis patients based on basic information. Grading statistics was used. Results Total number of vagrant psychosis patients and salvation needs increased year by year in Xi'an. Home return and social assistance were the main approaches for distributing characteristics of medical assistance. Conclusion The total number of vagrant psychosis patients is relative large. Such number is increasing year by year in Xi'an. A better treatment and diagnostic system for vagrant psychosis patients should be set up governmentally as quickly as possible.

Background and objective Artesunate, an anti-malarial drug, elicits an inhibitory effect on pulmonary carcinoma. However, the mechanisms of artesunate activity on pulmonary carcinoma have not been completely elucidated. hTe aim of this study is to investigate the effect of artesunate on the invasion of human lung adenocarcinoma A549 cells. Methods hTe inhibitory effect of artesunate on the proliferation and invasion of A549 cells was determined in vitro by MTT assay and transwell chamber invasion assay, respectively. A nude mouse model of human lung A549 cell xenogratf tumor was established. hTe inhibitory effect of artesunate on the tumor of the mouse model as well as ICAM-1 and MMP-9 protein expressions were determined by Western blot. Results A low dose of artesunate ranging between 1.25μg/L and 5μg/L did not signiifcantly inhibit the proliferation of A549 cells in vitro. By contrast, 1.25μg/L artesunate inhibited the invasion of A549 cells in vitro as determined by transwell chamber invasion assay (96.33±6.41 vs 75.43±4.37, P<0.05). Although 10 mg/kg artesunate did not signiifcantly inhibit A549 xenogratf tumor proliferation (P>0.05), artesunate decreased the ICAM-1 and MMP-9 protein levels in the mouse model (P<0.05). Conclusion Artesunate could inhibit the invasion of human lung adenocarcinoma A549 cells by possibly downregulating ICAM-1 and MMP-9 expressions.

Objective:To investigate the effect of ligand of numb-protein X1(LNX1)on the proliferation,invasion and migration of renal clear cell carcinoma cells and its underlying molecular mechanism. Methods:Gene Expression Profiling Interactive Analysis(GEPIA)database was used to analyze the mRNA expression level of LNX1 in renal clear cell carcinoma tissues and its relationship with the prognosis of patients with renal clear cell carcinoma.LNX1 gene specific shRNA(shLNX1)was delivered into renal clear cell carcinoma cell lines 786-O and ACHN by lentiviral infection,and flag-LNX1 plasmid was delivered into 786-O and ACHN cells by transient transfection.CCK-8 assay and colony formation assay were used to assess the effects of LNX1 silencing or overexpression on the proliferation of 786-O and ACHN cells.Transwell assay was used to evaluate the effects of LNX1 silencing or overexpression on the invasion and migration of 786-O and ACHN cells.Bioinformatics analysis was used to screen the downstream target genes of LNX1.Western blotting was used to examine the effects of LNX1 silencing or overexpression on the expression level of T-lymphoma invasion and metastasis-inducing protein 1(TIAM1)as well as the expression levels of total and phosphorylated ERK(phospho-ERK,p-ERK)in the ERK signaling pathway downstream of TIAM1 in 786-O and ACHN cells.786-O and ACHN cells overexpressing LNX1 were treated with proteasome inhibitor MG132,and the protein expression level of TIAM1 was analyzed by Western blotting.Finally,myc-TIAM1 recombinant plasmid was transfected into LNX1-overexpressing cells.Then,the expression levels of proteins in the ERK signaling pathway and the abilities of proliferation,invasion and migration of 786-O and ACHN cells were examined by Western blotting,colony formation assay and Transwell assay,respectively. Results:The mRNA expression level of LNX1 in renal clear cell carcinoma tissue was decreased(P＜0.05)and was positively correlated with the survival time of patients with renal clear cell carcinoma(P＜0.001).LNX1-silencing 786-O and ACHN cells and LNX1-overexpressing 786-O and ACHN cells were constructed successfully.After LNX1 silencing,the proliferation,invasion and migration of 786-O and ACHN cells were significantly enhanced(all P＜0.05).After LNX1 overexpression,the abilities of proliferation,invasion and migration of 786-O and ACHN cells were significantly decreased(all P＜0.05).Bioinformatics analysis identified TIAM1 as a potential target of LNX1.After silencing LNX1,the protein expression levels of TIAM1 and p-ERK were significantly increased(all P＜0.05),while the expression level of ERK remained unchanged.After LNX1 overexpression,the protein expression levels of TIAM1 and p-ERKwere significantly decreased(all P＜0.01),while the expression level of ERK was unchanged.Treatment with proteasome inhibitor MG132 increased the protein expression level of TIAM1 in LNX1-overexpressing 786-O and ACHN cells(P＜0.01 and P＜0.001).After LNX1-overexpressing cells were transfected with myc-TIAM1 plasmid,the protein expression level of p-ERK was increased,the abilities of cell proliferation,invasion and migration were enhanced(all P＜0.05),and the expression level of ERK protein remained unchanged. Conclusion:LNX1 inhibits the proliferation,invasion and migration of renal clear cell carcinoma cells by degrading TIAM1 which further regulates the phosphorylation of ERK.

Antimicrobial resistance has become a major public health issue of global concern. Conjugation is an important way for fast spreading drug-resistant plasmids, during which the type Ⅳ pili plays an important role. Type Ⅳ pili can adhere on the surfaces of host cell and other medium, facilitating formation of bacterial biofilms, bacterial aggregations and microcolonies, and is also a critical factor in liquid conjugation. PilV is an adhesin-type protein found on the tip of type Ⅳ pili encoded by plasmid R64, and can recognize the lipopolysaccharid (LPS) molecules that locate on bacterial membrane. The shufflon is a clustered inversion region that diversifies the PilV protein, which consequently affects the recipient recognition and conjugation frequency in liquid mating. The shufflon was firstly discovered on an IncI1 plasmid R64 and has been identified subsequently in plasmids IncI2, IncK and IncZ, as well as the pathogenicity island of Salmonella typhi. The shufflon consists of four segments including A, B, C, and D, and a specific recombination site named sfx. The shufflon is regulated by its downstream-located recombinase-encoding gene rci, and different rearrangements of the shufflon region in different plasmids were observed. Mobile colistin resistance gene mcr-1, which has attracted substantial attentions recently, is mainly located in IncI2 plasmid. The shufflon may be one of the contributors to fast spread of mcr-1. Herein, we reviewed the discovery, structure, function and prevalence of plasmid mediated shufflon, aiming to provide a theoretical basis on transmission mechanism and control strategy of drug-resistant plasmids.
Plasmids/genetics* ; Proteins/genetics* ; Bacteria/genetics* ; Recombinases ; Genes, Bacterial ; Anti-Bacterial Agents

Emergence of the colistin resistance gene,mcr-1,has attracted worldwide attention.Despite the prevalence of mcr-1-positive Escherichia coli(MCRPEC)strains in human carriage showing a significant decrease between 2016 and 2019,genetic differences in MCRPEC strains remain largely unknown.We therefore conducted a comparative genomic study on MCRPEC strains from fecal samples of healthy human subjects in 2016 and 2019.We identified three major differences in MCRPEC strains between these two time points.First,the insertion sequenceISApll1 was often deleted and the percentage of mcr-1-carrying IncI2 plasmids was increased in MCRPEC strains in 2019.Second,the antibiotic resistance genes(ARGs),aac(3)-Ⅳa and blaCTX-M-1,emerged and coexisted with mcr-1 in 2019.Third,MCRPEC strains in 2019 contained more viru-lence genes,resulting in an increased proportion of extraintestinal pathogenic E.coli(ExPEC)strains(36.1％)in MCRPEC strains in 2019 compared to that in 2016(10.5％),implying that these strains could occupy intestinal ecological niches by competing with other commensal bacteria.Our results suggest that despite the significant reduction in the prevalence of MCRPEC strains in humans from 2016 to 2019,MCRPEC exhibits increased resistance to other clinically important ARGs and contains more virulence genes,which may pose a potential public health threat.

The widespread of tigecycline resistance gene tet(X4) has a serious impact on the clinical efficacy of tigecycline. The development of effective antibiotic adjuvants to combat the looming tigecycline resistance is needed. The synergistic activity between the natural compound β-thujaplicin and tigecycline in vitro was determined by the checkerboard broth microdilution assay and time-dependent killing curve. The mechanism underlining the synergistic effect between β-thujaplicin and tigecycline against tet(X4)-positive Escherichia coli was investigated by determining cell membrane permeability, bacterial intracellular reactive oxygen species (ROS) content, iron content, and tigecycline content. β-thujaplicin exhibited potentiation effect on tigecycline against tet(X4)-positive E. coli in vitro, and presented no significant hemolysis and cytotoxicity within the range of antibacterial concentrations. Mechanistic studies demonstrated that β-thujaplicin significantly increased the permeability of bacterial cell membranes, chelated bacterial intracellular iron, disrupted the iron homeostasis and significantly increased intracellular ROS level. The synergistic effect of β-thujaplicin and tigecycline was identified to be related to interfere with bacterial iron metabolism and facilitate bacterial cell membrane permeability. Our studies provided theoretical and practical data for the application of combined β-thujaplicin with tigecycline in the treatment of tet(X4)-positive E. coli infection.
Humans ; Tigecycline/pharmacology* ; Escherichia coli/metabolism* ; Reactive Oxygen Species/therapeutic use* ; Plasmids ; Anti-Bacterial Agents/metabolism* ; Escherichia coli Infections/microbiology* ; Bacteria/genetics* ; Microbial Sensitivity Tests