Overexpression of LCMR1 is significantly associated with clinical stage in human NSCLC

<p>Abstract</p> <p>Background</p> <p>Lung cancer is one of the most common human cancers and the leading cause of cancer death worldwide. The identification of lung cancer associated genes is essential for lung cancer diagnosis and treatment.</p> <p>Methods</p> <p>Differential Display-PCR technique was used to achieve the novel cDNA, which were then verified by real-time PCR. Northern blot was utilized to observe the expression of LCMR1 in different human tissues. 84 cases human NSCLC tissues and normal counterparts were analyzed for the expression of LCMR1 by immunohistochemistry.</p> <p>Results</p> <p>A novel 778-bp cDNA fragment from human large cell lung carcinoma cell lines 95C and 95D was obtained, and named <it>LCMR1 </it>(Lung Cancer Metastasis Related protein 1). LCMR1 was differentially expressed in different human tissues. LCMR1 was strongly overexpressed in NSCLC and its expression was significantly associated with clinical stage.</p> <p>Conclusion</p> <p>Our data indicated that <it>LCMR1</it>, strongly overexpressed in NSCLC, might have applications in the clinical diagnosis and treatment of lung cancer.</p

Post-ERCP infection and its epidemiological and clinical characteristics in a large Chinese tertiary hospital: a 4-year surveillance study

Abstract Background Endoscopic retrograde cholangiopancreatography (ERCP) is widely performed as a treatment for biliary and pancreatic illness in China; however, there are few data available regarding post-ERCP infections. This study aimed to describe the overall incidence of post-ERCP infections and the epidemiological characteristics of infected patients in a large tertiary-care hospital in China. Methods Real-time surveillance was performed from 2012 through 2015 to identify all healthcare-associated infections (HAIs) that occurred after ERCP, using an automatic system. All HAIs (e.g., cholangtitis, bacteremia) were identified by infection control practitioners and doctors. Inpatient data were automatically collected by the surveillance system. Results A total of 1743 ERCP operations were included in the study, among these, 132 (7.57%) HAIs were identified. ERCP postoperative infections occurred following different surgical procedures, with infection rates ranging from 3.58 to 13.51%. The most prevalent HAI was biliary tract infection (4.02%), followed by transient bacteremia (1.14%). Overall, 62 cases of bacteremia occurred following ERCP surgery and 34 (54.84%) cases occurred on the day of the operation or 1-day post-surgery. The most prevalent isolates detected during bacteremia were Enterococcus faecium (12/58) and Escherichia coli (11/58). A large proportion (72.73%) of the E. coli isolates and all of the E. faecium isolates were resistant to ciprofloxacin. In addition, only 37.50% of the E. coli isolates were susceptible to ceftriaxone. Conclusions The high incidence of post-ERCP infection and the prevalence of drug resistance suggests that employing second generation cephalosporin or ceftriaxone as the antibiotic of choice for prophylaxis before ERCP, as recommended by the Chinese clinical application of antibacterial drugs guidelines, may not be effective

Clinical characteristics of patients with Ochrobactrum anthropi bloodstream infection in a Chinese tertiary-care hospital: A 7-year study

Background: Ochrobactrum anthropi has become an emerging pathogen for bloodstream infection (BSI). Methods: From January 1st 2010 to June 30th 2017, inpatients with one or more blood cultures positive for O. anthropi isolates at Chinese People’s Liberation Army General Hospital in Beijing, China, were enrolled in this study. Clinical and laboratory data were collected by reviewing electronic records. Results: A total of 11 patients with O. anthropi BSI were identified, of which 10 patients survived. There were 6 males and 5 females, whose age ranged from 2 to 83 years. 7 infections were hospital-acquired. In 8 cases O. anthropi was the only pathogen. The most common symptoms of O. anthropi BSI were fever (100%) and disorders of consciousness (45.5%). All patients had undergone indwelling catheter placement. O. anthropi isolates in this study were most susceptible to levofloxacin (100%), ciprofloxacin (85.7%), imipenem (85.7%) and cotrimoxazole (85.7%), while they were widely resistant to penicillins and cephalosporins. Conclusions: O. anthropi BSI usually happens in patients with indwelling catheters, and often begins with no distinctive symptom or laboratory finding. O. anthropi seldom form polymicrobial BSIs. Quinolones and carbapenems are optimal antibiotics for O. anthropi BSI. Catheter removal is essential when O. anthropi BSI happens recurrently. Keywords: Ochrobactrum anthropi, Bloodstream infection, Clinical characteristics, Antimicrobial susceptibility tes

Epidemiology and microbiology of Gram-positive bloodstream infections in a tertiary-care hospital in Beijing, China: a 6-year retrospective study

Abstract Background Gram-positive bacterial bloodstream infections (BSIs) are serious diseases associated with high morbidity and mortality. The following study examines the incidence, clinical characteristics and microbiological features, drug resistance situations and mortality associated with Gram-positive BSIs at a large Chinese tertiary-care hospital in Beijing, China. Methods A retrospective cohort study of patients with Gram-positive BSIs was performed between January 1, 2011, and June 31, 2017, at the Chinese People’s Liberation Army General Hospital. The patients’ data were collected and included in the reviewing electronic medical records. Results A total of 6887 episodes of Gram-positive BSIs occurred among 4275 patients over 6 years, and there were 3438 significant BSI episodes 69% of these cases were healthcare-associated, while 31% were community-associated. The overall incidence of Gram-positive BSIs fluctuated from 7.26 to 4.63 episodes per 1000 admissions over 6 years. Malignancy was the most common comorbidity and indwelling central intravenous catheter was the most common predisposing factor for BSI. Staphylococci were the major pathogen (65.5%), followed by Enterococcus spp:(17.5%), Streptococcus spp.(7.1%) and other bacterial pathogens (9.9%). The resistance rates of Staphylococci and E.faecium to penicillins were more than 90%. the vancomycin-resistant isolates were E. faecium (4.1%) and staphylococcus epidermidis (0.13%); and only E.faecalis and E.faecium showed resistance to linezolid (3.8% and 3.1%). Between 2011 and 2017, the overall mortality of Gram-positive BSIs decreased from 6.27 to 4.75% (X2 = 0.912, p = 0.892). Neverthess, the mortality in the ICU decreased from 60.46 to 47.82%, while in the general ward it increased from 39.54 to 52.18%. Conclusions The morbidity and mortality of Gram-positive BSIs have showed downward trends. Vancomycin and linezolid are still consider the best treatment for patients with Gram-positive BSIs

Community-acquired necrotizing pneumonia caused by methicillin-resistant Staphylococcus aureus producing Panton–Valentine leukocidin in a Chinese teenager: case report and literature review

Background: Methicillin-resistant Staphylococcus aureus (MRSA) has now been established as an important community-acquired pathogen. Although necrotizing pneumonia caused by community-acquired MRSA (CA-MRSA) strains producing Panton–Valentine leukocidin (PVL) has been reported with increasing frequency in many countries, it has been reported in only a few children younger than 1 year of age in Mainland China. Methods: We describe a case of life-threatening necrotizing pneumonia due to PVL-positive CA-MRSA in a 15-year-old previously healthy female who presented with high fever, shivering, a dry cough, and dyspnea. Details of the clinical outcomes, microbiological data, and therapies for this patient were collected and compared with those of cases reported in the literature on CA-MRSA. Results: Computed tomography (CT) findings showed cavitary consolidations in both lungs and bilateral pleural effusion. MRSA strains isolated from the patient's sputum and pleural fluid were susceptible to most non-β-lactam antimicrobial agents except for clindamycin and erythromycin. Both of these isolates tested positive for the mecA gene as well as PVL genes, and were identified as ST59-MRSA-SCCmec type IV-spa type t437. The patient was treated successfully with linezolid, fosfomycin, and teicoplanin. Conclusions: To our knowledge, this is the first report from Mainland China of necrotizing pneumonia due to PVL-positive CA-MRSA among those aged older than 1 year. CA-MRSA necrotizing pneumonia should be considered in the differential diagnosis of severe community-acquired pneumonia, particularly in previously healthy individuals

LCMR1 Promotes Large-Cell Lung Cancer Proliferation and Metastasis by Downregulating HLA-Encoding Genes

Lung cancer is notorious for its high global morbidity and mortality. Here, we examined whether the LCMR1 gene, which we previously cloned from a human large-cell lung carcinoma cell line, contributes to the proliferation and metastasis of large-cell lung carcinoma. To this end, we performed pan-cancer and non-small cell lung cancer (NSCLC) cell line-based LCMR1 expression profiling. Results revealed that LCMR1 was expressed at high levels in most solid tumors, including NSCLC. LCMR1 expression was the highest in the 95D large cell lung cancer cell line. Functional studies using lentivirus-based knockdown revealed that LCMR1 was critical for the proliferation, migration, and invasion of cultured large cell lung cancer cells. Moreover, blocking this gene significantly reduced tumor growth in a 95D cell xenograft mouse model. A multiple sequence-based assay revealed a mechanism by which LCMR1 diminished the RNA Pol II occupancy at the promoter of human leukocyte antigen (HLA)-encoding genes to prevent their transcription. The HLA genes play vital roles in cancer-specific antigen presentation and anticancer immunity. A correlation assay using TCGA database identified a negative relationship between the expression levels of LCMR1 and HLA coding genes. Taken together, our findings demonstrate that LCMR1 is required for large cell lung cancer cell growth and invasion and suggest its potential as a valid target in clinical treatment

Mesenchymal Stem Cell Conditioned Medium Promotes Proliferation and Migration of Alveolar Epithelial Cells under Septic Conditions In Vitro via the JNK-P38 Signaling Pathway

Background/Aims: Mesenchymal stem cell (MSC) based therapies may be useful for treating acute respiratory distress syndrome (ARDS), but the underlying mechanisms are incompletely understood. We investigated the impact of human umbilical cord Wharton's jelly-derived MSC (hUC-MSC) secreted factors on alveolar epithelial cells under septic conditions and determined the relevant intracellular signaling pathways. Methods: Human alveolar epithelial cells (AEC) and primary human small airway epithelial cells (SAEC) were subjected to lipopolysaccharide (LPS) with or without the presence of hUC-MSC-conditioned medium (CM). Proliferation and migration of AEC and SAEC were determined via an MTT assay, a wound healing assay and a transwell migration assay (only for AEC). Protein phosphorylation was determined by western blot and the experiments were repeated in presence of small-molecule inhibitors. The hMSC-secretory proteins were identified by LC-MS/MS mass spectrometry. Results: MSC-CM enhanced proliferation and migration. Activation of JNK and P38, but not ERK, was required for the proliferation and migration of AEC and SAEC. Pretreatment of AEC or SAEC with SP600125, an inhibitor of JNK1 or SB200358, an inhibitor of P38, significantly reduced cell proliferation and migration. An array of proteins including TGF-beta receptor type-1, TGF-beta receptor type-2, Ras-related C3 botulinum toxin substrate 1 and Ras-related C3 botulinum toxin substrate 2 which influencing the proliferation and migration of AEC and SAEC were detected in MSC-CM. Conclusion: Our data suggest MSC promote epithelial cell repair through releasing a repertoire of paracrine factors via activation of JNK and P38 MAPK

Keratinocyte Growth Factor Gene Delivery via Mesenchymal Stem Cells Protects against Lipopolysaccharide-Induced Acute Lung Injury in Mice

<div><p>Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with high morbidity and mortality, and have no specific therapy. Keratinocyte growth factor (KGF) is a critical factor for pulmonary epithelial repair and acts via the stimulation of epithelial cell proliferation. Mesenchymal stem cells (MSCs) have been proved as good therapeutic vectors. Thus, we hypothesized that MSC-based KGF gene therapy would have beneficial effects on lipopolysaccharide(LPS)-induced lung injury. After two hours of intratracheal LPS administration to induce lung injury, mice received saline, MSCs alone, empty vector-engineered MSCs (MSCs-vec) or KGF-engineered MSCs (MSCs-kgf) via the tail vein. The MSCs-kgf could be detected in the recipient lungs and the level of KGF expression significantly increased in the MSCs-kgf mice. The MSC-mediated administration of KGF not only improved pulmonary microvascular permeability but also mediated a down-regulation of proinflammatory responses (reducing IL-1β and TNF-α) and an up-regulation of anti-inflammatory responses (increasing cytokine IL-10). Furthermore, the total severity scores of lung injury were significantly reduced in the MSCs-kgf group compared with the other three groups. The underlying mechanism of the protective effect of KGF on ALI may be attributed to the promotion of type II lung epithelial cell proliferation and the enhancement of surfactant synthesis. These findings suggest that MSCs-based KGF gene therapy may be a promising strategy for ALI treatment.</p></div