Kaifei Wang

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.

Predictive value of procalcitonin for excluding bloodstream infection: Results of a retrospective study and utility of a rapid, quantitative test for procalcitonin

Objectives To assess retrospectively the diagnostic value of procalcitonin (PCT) in excluding suspected bloodstream infection, establish cut-off values for PCT levels, and compare PCT with other clinical markers. Methods The predictive accuracy of different continuous parameters was estimated by univariate analysis of the area under the receiver operating characteristic curve. Optimized cut-off points for the parameters were selected according to the maximum Youden index values, which in turn were used to define positive and negative predictive values of different parameters in diagnosing bloodstream infection. Results The PCT level yielded a statistically significant area under the receiver operating characteristic curve of 0.765, with a best cut-off value of 0.80 ng/ml (83% sensitivity; 65% specificity, Youden index, J = 0.48). Positive and negative predictive values at this cut-off value were 38% and 94%, respectively. Mann–Whitney U-test revealed significantly higher values for PCT, C-reactive protein and percentage of neutrophils, but not for white blood cell count, in patients with bloodstream infection. Conclusions The serum PCT level can potentially be used as surrogate marker to exclude bacteraemia and to inform critical management decisions regarding antibiotic usage, in patients admitted with suspected bloodstream infection.

Clinical and microbiological characterization of Staphylococcus lugdunensis isolates obtained from clinical specimens in a hospital in China.

BackgroundSeveral reports have associated Staphylococcus lugdunensis with the incidence of severe infection in humans; however, the frequency and prevalence of this microorganism and thus the propensity of its antimicrobial drug resistance is unknown in China. The objective of the current study was to determine the prevalence of Staphylococcus lugdunensis among six hundred and seventy non-replicate coagulase negative Staphylococcus (CoNS) isolates collected in a 12-month period from clinical specimens in the General Hospital of the People’s Liberation Army in Beijing, China.ResultsFive (0.7%) of the 670 isolates of CoNS were identified as S. lugdunensis. Whereas three isolates were resistant to erythromycin, clindamycin, and penicillin and carried the ermC gene and a fourth one was resistant to cefoxitin and penicillin and carried the mecA gene, one isolate was not resistant to any of the tested antimicrobials. Pulse field gel electrophoretic analysis did not reveal widespread epidemiological diversity of the different isolates.ConclusionHence, even though S. lugdunensis may be yet unrecognized and undefined in China, it still might be the infrequent cause of infection and profound multi-drug resistance in the same population.

Comparative study of solitary thin-walled cavity lung cancer with computed tomography and pathological findings

BACKGROUND Solitary thin-walled cavity lung cancer is a specific form of lung cancer, the diagnosis of which remains a formidable challenge. OBJECTIVE By comparing the computed tomography (CT) presentations and pathological findings, the purpose of present study was to explain the possible mechanism of thin-walled cavity formation and to improve the diagnostic accuracy for this disease. METHODS The medical records of eighteen patients with solitary thin-walled cavity lung cancer were analyzed retrospectively. RESULTS Chest CT demonstrated that solitary thin-walled cavities located at pulmonary periphery, and all these cavity lesions displayed suspected malignant signs. Pathological findings after surgery confirmed these lesions were adenocarcinoma, most of which were moderately or well differentiated. Microscopic findings showed tumor cells proliferated in the surface of thin-wall cavity in nine patients and infringed bronchiolar wall in five patients. No obvious necrotic tumor cell was observed in each patient. CONCLUSION It was suggested some thin-walled cavities may be formed as a result of unidirectional check-valve mechanism. Together, a high index of awareness of this suspected CT signs is required for early diagnosis of this disease.

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.

Gefitinib in combination with prednisolone to avoid interstitial lung disease during non-small cell lung cancer treatment: A case report

Gefitinib-induced interstitial lung disease (ILD) is a rare but lethal drug adverse event, which usually leads to the withdrawal of gefitinib and causes complications with anticancer treatment. In this study, gefitinib administration combined with prednisolone in a female with stage IIIb non-small cell lung cancer (NSCLC) produced a good outcome without inducing ILD. The results suggested that combined administration of gefitinib with glucocorticoids may be an efficient method to treat NSCLC while avoiding complications with ILD.

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.