Xinying Xue

Plasmid-mediated quinolone resistance – current knowledge and future perspectives

Quinolones are a group of antimicrobial agents that were serendipitously discovered as byproducts of the synthesis of chloroquine. Chemical modifications, such as the addition of fluorine or piperazine, resulted in the synthesis of third- and fourth-generation fluoroquinolones, with broad-spectrum antimicrobial actions against aerobic or anaerobic, Gram-positive or Gram-negative bacteria. The efficacy and consequent widespread use of quinolones and fluoroquinolones has led to a steady global increase in resistance, mediated via gene mutations, alterations in efflux or cell membranes and plasmid-conferred resistance. The first plasmid-mediated quinolone resistance gene, qnrA1, was detected in 1998. Since then, many other genes have been identified and the underlying mechanisms of resistance have been elucidated. This review provides an overview of quinolone resistance, with particular emphasis on plasmid-mediated resistance.

MiR-21 and MiR-155 promote non-small cell lung cancer progression by downregulating SOCS1 , SOCS6 , and PTEN

Lung cancer remains the leading cause of cancer-associated death worldwide. MiR-21 and miR-155 are the most amplified miRNAs in non-small cell lung carcinoma (NSCLC), and are critical promoters of NSCLC progression. However, it remains unclear how miR-21 and miR-155 induce cancer progression, and whether these miRNAs share common targets, such as tumor suppressor genes required to prevent NSCLC. Here we report that miR-21 and miR-155 levels are elevated in NSCLC and are proportional to the progression of the disease. In addition, miR-21 and miR-155 share nearly 30% of their predicted target genes, including SOCS1, SOCS6, and PTEN, three tumor suppressor genes often silenced in NSCLC. Consequently, antagonizing miR-21, miR-155 or both potently inhibited tumor progression in xenografted animal models of NSCLC. Treatment with miR-21 and miR-155 inhibitors in combination was always more effective against NSCLC than treatment with a single inhibitor. Furthermore, levels of miR-21 and miR-155 expression correlated inversely with overall and disease-free survival of NSCLC patients. Our findings reveal that miR-21 and miR-155 promote the development of NSCLC, in part by downregulating SOCS1, SOCS6, and PTEN. Combined inhibition of miR-21 and miR-155 could improve the treatment of NSCLC.

Diagnosis of multiple primary lung cancer: A systematic review

A substantial percentage (8%) of all newly diagnosed cancer cases are in patients with previous tumours, with a similar trend in lung cancer. Cases of multiple primary lung cancer (MPLC) are increasing worldwide, due to improved diagnostic and surveillance mechanisms and the ageing population. Diagnosis of MPLC is complicated by difficulties in distinguishing it from lung cancer metastasis. Clinicopathological assessment, diagnosis and management have evolved, but remain severely limited by the lack of robust and dependable molecular markers for the differential diagnosis of metastasis and MPLC. This systematic review evaluates diagnostic criteria for MPLC, and the subsequent management and success rates. The incorporation of molecular biology techniques into the diagnostic process for MPLC is also discussed.

Comparison of pyogenic liver abscesses caused by hypermucoviscous Klebsiella pneumoniae and non-Klebsiella pneumoniae pathogens in Beijing: A retrospective analysis

Objective To perform a retrospective comparison of the clinical and radiological features of Klebsiella pneumoniae (KP)-associated and non-KP-associated pyogenic liver abscesses (PLA) in Chinese patients. Methods Patients with confirmed diagnoses of bacterial liver abscess at three Beijing hospitals were enrolled. Clinical isolates from liver abscesses were used to determine serology and expression of hypermucoviscosity genes. Basic clinical, ultrasonographic (US) and computed tomography (CT) data were recorded and compared between patients with KP- and non-KP-associated PLA. Results A total of 101 (77.10%) and 30 (22.90%) cases were due to KP and non-KP pathogens, respectively. Compared with the non-KP cohort, the KP cohort demonstrated a significantly higher incidence of underlying diabetes mellitus, and more gas-forming abscesses, as demonstrated by US and CT examinations. Prior abdominal surgery or chemoradiation therapy was significantly associated with non-KP cases. The non-KP group had a higher chance of a clear edge, compared with the KP group, on pre-contrast CT images. Conclusion KP and non-KP-associated PLA have distinctive risk factors and unique US and CT features, in Chinese patients.

Polypoid colonic metastases from gastric stump carcinoma: A case report

The present study aimed to investigate polypoid colonic metastases from gastric stump carcinoma by performing a retrospective analysis of the clinical data of a patient with such a diagnosis, and by discussing other previous case studies from the literature. The patient of the present study was an 80-year-old male who had undergone a gastrectomy 48 years previously for a benign perforated gastric ulcer. A colonoscopy revealed >10 multiple polypoid lesions of 6–10 mm in diameter distributed throughout the entire colon, except in the rectum. Each lesion had either erosion or a depression at the top and several were covered with a white fur-like substance. Biopsy specimens excised from the stomach showed a poorly-differentiated adenocarcinoma with diffuse signet ring cells, and a colonoscopy-guided biopsy revealed a signet ring cell adenocarcinoma. The patient was referred to the Oncology unit (Beijing Shijitan Hospital, Beijing, China) for assessment and chemotherapy treatment, which was initiated with 1,000 mg Xeloda orally administered twice a day for two-week courses every three weeks. The patient succumbed to upper gastrointestinal hemorrhage and pneumonia after three months. Gastric or gastric stump carcinoma may metastasize to the colon presenting as solitary or multiple colonic polyps. Thus, it is important to consider this diagnosis as such colon metastases may mimic solitary or multiple colonic polyps, which are commonly observed. A differential diagnosis is required in this complicated situation.

Pulmonary Arterial Hypertension and MicroRNAs—An Ever-growing Partnership

Pulmonary arterial hypertension (PAH) is a debilitating condition with progressive remodeling of the pulmonary resistance vessels. PAH is characterized by multifocal, polyclonal lesions inhabited by cells that underwent phenotypic transition, resulting in altered cell proliferation and contractility, ultimately resulting in increased vascular resistance. Diagnosis of PAH is confounded by the fact that it is largely asymptomatic in the initial stages. In fact, idiopathic PAH patients >65 years of age cannot be diagnosed hemodynamically due to high pulmonary capillary wedge pressure. This highlights the need for defining more robust molecular biomarkers for PAH diagnosis and progression. Recent studies have indicated that microRNAs (miRNAs), a class of small noncoding RNAs that regulate gene expression, play a discrete role in vascular inflammation and in the etiology of cardiovascular pathologies inclusive of PAH and can potentially serve as diagnostic biomarkers. However, a cohesive understanding of global miRNA-mediated molecular events that control pulmonary vasculature plasticity is lacking which, if addressed systematically, can lead to detailed elucidation of the downstream cellular pathways that are affected by activation/silencing of silenced cognate transcripts. In turn, this can lead to not only robust biomarkers, but also to novel therapeutic strategies targeting more upstream regulators than the existing ones targeting more downstream effectors. The current review aims to provide a summary understanding of PAH, its associated pathophysiology, current knowledge of the role of miRNAs in PAH, and identifies grey areas that need further research for successful bench-to-bedside transition of these exciting new discoveries.

CXCL10/IP-10 Neutralization Can Ameliorate Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome in Rats

The role of C-X-C motif chemokine 10 (CXCL10), a pro-inflammatory factor, in the development of acute respiratory distress syndrome (ARDS) remains unclear. In this study, we explored the role of CXCL10 and the effect of CXCL10 neutralization in lipopolysaccharide (LPS)-induced ARDS in rats. The expression of CXCL10 and its receptor chemokine receptor 3(CXCR3) increased after LPS induction. Moreover, neutralization of CXCL10 ameliorated the severity of ARDS by reducing pulmonary edema, inhibiting the release of inflammatory mediators (IFN-γ, IL-6 and ICAM-1) and limiting inflammatory cells (neutrophils, macrophages, CD8+ T cells) influx into the lung, with a reduction in CXCR3 expression in neutrophils and macrophages. Therefore, CXCL10 could be a potential therapeutic target in LPS-induced ARDS.

Bone marrow stromal cells induced activation of nuclear factor κB signaling protects non-Hodgkin’s B lymphoma cells from apoptosis

The microenvironment encompassing a variety of non-malignant cells in close proximity with malignant tumor cells has been well known to significantly affect the behavior of tumor cells. In this study, we therefore studied the mechanism of bone marrow stromal cells in protection of lymphoma cells from spontaneous apoptosis. We demonstrated that adhesion of the freshly isolated lymphoma B cells to bone marrow stromal cells or freshly isolated lymphoma stromal cells inhibited B cell spontaneous apoptosis in culture. This inhibition of apoptosis correlated with decreased cleavage of caspase-3/8 and increased activation of canonical and non-canonical NF-κB signaling pathway. In addition to BAFF signaling which has been reported as a functional determinant for B lymphoma cell survival in the bone marrow environment, we demonstrated RANKL from BMSCs works synergistically with BAFF to activate NF-κB signaling pathway and thus protects lymphoma B cells from spontaneous apoptosis.

Computed Tomography for the Diagnosis of Solitary Thin-Walled Cavity Lung Cancer.

Lung cancer is the most commonly diagnosed neoplasm and the leading cause of cancer‐related death worldwide. Despite the high incidence of lung cancer, the diagnosis of solitary thin‐walled cavity lung cancer is rare. The aim of this review is to explore the potentials of computed tomography (CT) as diagnostic tool for solitary thin‐walled cavity lung cancer.

Thin‑wall cystic lung cancer: A study of 45 cases

Thin-wall cystic lung cancer is uncommon. Consequently, there is a lack of knowledge concerning the features of this type of lung cancer, which may lead to misdiagnosis and delayed treatment. The aim of the present study is to understand the invasiveness and metastasis of thin-wall cystic lung cancer. The prognosis of this type of cancer will also be discussed. The present study attempted to determine the pathological interpretation of the imaging results. A total of 45 patients with this specific type of lung cancer were analyzed retrospectively based on the review of medical records, radiological findings, pathological changes and treatment strategies. Certain patients were also telephoned in order to learn about their recent physical conditions. Thin-wall cystic lung cancer displayed suspected malignant signs. The majority of these cases are adenocarcinoma, but certain cases of squamous cell carcinoma may also display cysts on their images. Although thin-wall cystic lung cancer is often thought to progress slowly, certain cases may progress rapidly. Distant metastasis, which is relatively rare, occurred in three cases. Cancer cells proliferate along the terminal bronchioles and destroy the lung tissues exposing the bronchial arteries and adjacent bronchi. Therefore, separation in cysts on the images was observed. In the majority of cases, the thin-wall cystic lung cancer proliferates slowly, but in a few cases it may be very aggressive.