Jindong Shi

A Detailed Epidemiological and Clinical Description of 6 Human Cases of Avian-Origin Influenza A (H7N9) Virus Infection in Shanghai

Background The world’s first reported patient infected with avian influenza H7N9 was treated at the Fifth People’s Hospital of Shanghai. Shortly thereafter, several other cases emerged in the local area. Here, we describe the detailed epidemiological and clinical data of 6 cases of avian influenza H7N9. Methods and Findings We analyzed the epidemiologic and clinical data from clustered patients infected with H7N9 in the Minhang District of Shanghai during a 2-week period. Of the 6 patients, 2 were from a single family. In addition, 3 patients had a history of contact with poultry; however, all 6 patients lived in the proximity of 2 food markets where the H7N9 virus was detected in chickens and pigeons. The main symptoms were fever, cough, and hemoptysis. At onset, a decreased lymphocyte count and elevated creatine kinase, lactate dehydrogenase, procalcitonin, and C-reactive protein levels were observed. As the disease progressed, most patients developed dyspnea and hypoxemia. Imaging studies revealed lung consolidation and multiple ground-glass opacities in the early stage, rapidly extending bilaterally. All patients were treated with oseltamivir tablets beginning on days 3–8 after onset. The main complications were as follows: acute respiratory distress syndrome (ARDS; 83.3%), secondary bacterial infection (66.7%), pleural effusion (50%), left ventricular failure (33.3%), neuropsychiatric symptoms (33.3%), and rhabdomyolysis (16.7%). Of the 6 patients, 4 died of ARDS, with 2 patients recovering from the infection. Conclusions An outbreak of H7N9 infection occurred in the Minhang District of Shanghai that easily progressed to acute respiratory distress syndrome. Two cases showed family aggregation, which led us to identify the H7N9 virus and indicated that human transmission may be involved in the spread of this infection.

MicroRNA-141 promotes the proliferation of non-small cell lung cancer cells by regulating expression of PHLPP1 and PHLPP2

The dysregulation of microRNAs (miRNAs) is crucially implicated in the development of various cancers. In this study, we explored the biological role of miR‐141 in non‐small cell lung cancer (NSCLC). miR‐141 expression was significantly up‐regulated in NSCLC tissues, and its overexpression accelerated NSCLC cell proliferation in vitro and tumor growth in vivo. We subsequently identified the antagonists of PI3K/AKT signaling, PH domain leucine‐rich‐repeats protein phosphatase 1 (PHLPP1) and PHLPP2, as direct targets of miR‐141. Re‐introduction of PHLPP1 and PHLPP2 abrogated miR‐141‐induced proliferation of NSCLC cells. Together, the results of this study suggest that miR‐141 and its targets PHLPP1 and PHLPP2 play critical roles in NSCLC tumorigenesis, and provide potential therapeutic targets for NSCLC treatment.

Family Outbreak of Severe Pneumonia Induced by H7N9 Infection

monary function impairment. These findings from their patient cohort are consistent with the experience of the BAL guideline committee members in their clinical practice when BAL is used to evaluate patients with suspected ILD (1). Although significant complications have been associated with the performance of diagnostic BAL in patients with a suspected or established diagnosis of ILD (2, 3), such complications are rare. BAL not only has been widely used in patients with suspected ILD, but it can be used safely in patients with airway disorders (e.g., asthma or bronchiectasis) or lung transplant recipients when protocols are in place to ensure that adequate precautions are taken to maintain adequate monitoring throughout the procedure and during the post-procedure recovery period (4–6). It was our hope that the publication of this guideline would (1) enhance the safety and efficacy of BAL as a useful clinical tool for the evaluation of patients with suspected ILD, (2) lead to better standardization of the BAL procedure when performed in centers around the world, and (3) increase recognition of the potential for BAL cell analysis to enhance clinicians’ ability to make a confident diagnosis of specific forms of ILD in the appropriate clinical setting. When BAL is properly performed and analyzed, the BAL cell differential count can provide very useful diagnostic information when combined with clinical findings and appropriate thoracic high-resolution computed tomography imaging (1, 7). The study by Agarwal and colleagues nicely demonstrates that BAL can be performed safely with adequate retrieval of lavage fluid for subsequent analysis when a protocol consistent with the ATS clinical practice guideline is used.

Association between genetic polymorphisms in XPD and XRCC1 genes and risks of non-small cell lung cancer in East Chinese Han population.

Lung cancer is a multifactorial disease. Xeroderma pigmentosum group D (XPD) and X‐ray repair cross‐complementing 1 (XRCC1) genes are 2 important susceptibility genes related to lung cancer. In this study, we explored the correlation between genetic polymorphisms in XPD and XRCC1 and the risk of non‐small cell lung cancer (NSCLC) in the East Chinese Han population. We also investigated risk factors associated with non‐small cell lung cancer in this population.

MAML2 rearrangement in primary pulmonary mucoepidermoid carcinoma and the correlation with FLT1 expression.

Introduction Primary pulmonary mucoepidermoid carcinoma (PMEC) is an uncommon neoplasm with remarkable resemblance to mucoepidermoid carcinoma of the salivary glands. The latter has been shown to harbor t(11,19) resulting in MECT1-MAML2 fusion, which may be of diagnostic and prognostic values. However, the importance of such feature in PMEC has not been well studied. Methods We detected MAML2 rearrangement using fluorescence in situ hybridization (FISH) in tissue samples from 42 cases of PMEC and 40 of adenosquamous carcinoma (ASC), and the expression of potential downstream targets of MECT1-MAML2, including HES1, FLT1 and NR4A2 with immunohistochemistry (IHC). The findings were then examined regarding the clinicopathological parameters and patient outcomes. Results FISH analysis revealed MAML2 rearrangement in 50% of the PMEC cases, and such property was prominent in considerable younger patients (33 versus 60 years; p = 0.001) and restricted to cases of low and intermediate grades. IHC analysis showed that FLT1 and HES1 were expressed at lower level in MAML2 rearranged group than MAML2 non-rearranged group (p<0.001 and p = 0.023, respectively). Survival analysis showed significant correlation between MAML2 rearrangement and overall survival (p = 0.023) or disease-free survival (p = 0.027) as well as correlation between FLT1 and overall survival (p = 0.009). Conclusions MAML2 rearrangement appears frequent in PMEC and specific with this tumor. Both the presence of MAML2 rearrangement and absence of FLT1 tend to confer a favorable clinical outcome. These findings suggest that molecular detection of MAML2 rearrangement combined with FLT1 may be of important clinical value for PMEC.

Bone-marrow-derived mesenchymal stem cells inhibit gastric aspiration lung injury and inflammation in rats

Gastric aspiration lung injury is one of the most common clinical events. This study investigated the effects of bone‐marrow‐derived mesenchymal stem cells (BMSCs) on combined acid plus small non‐acidified particle (CASP)‐induced aspiration lung injury. Enhanced green fluorescent protein (EGFP+) or EGFP− BMSCs or 15d‐PGJ2 were injected via the tail vein into rats immediately after CASP‐induced aspiration lung injury. Pathological changes in lung tissues, blood gas analysis, the wet/dry weight ratio (W/D) of the lung, levels of total proteins and number of total cells and neutrophils in bronchoalveolar lavage fluid (BALF) were determined. The cytokine levels were measured using ELISA. Protein expression was determined by Western blot. Bone‐marrow‐derived mesenchymal stem cells treatment significantly reduced alveolar oedema, exudation and lung inflammation; increased the arterial partial pressure of oxygen; and decreased the W/D of the lung, the levels of total proteins and the number of total cells and neutrophils in BALF in the rats with CASP‐induced lung injury. Bone‐marrow‐derived mesenchymal stem cells treatment decreased the levels of tumour necrosis factor‐α and Cytokine‐induced neutrophil chemoattractant (CINC)‐1 and the expression of p‐p65 and increased the levels of interleukin‐10 and 15d‐PGJ2 and the expression of peroxisome proliferator‐activated receptor (PPAR)‐γ in the lung tissue in CASP‐induced rats. Tumour necrosis factor‐α stimulated BMSCs to secrete 15d‐PGJ2. A tracking experiment showed that EGFP+ BMSCs were able to migrate to local lung tissues. Treatment with 15d‐PGJ2 also significantly inhibited CASP‐induced lung inflammation and the production of pro‐inflammatory cytokines. Our results show that BMSCs can protect lung tissues from gastric aspiration injury and inhibit lung inflammation in rats. A beneficial effect might be achieved through BMSC‐derived 15d‐PGJ2 activation of the PPAR‐γ receptor, reducing the production of proinflammatory cytokines.

Targeted blockade of TGF-β and IL-6/JAK2/STAT3 pathways inhibits lung cancer growth promoted by bone marrow-derived myofibroblasts

To investigate the role of TGF-β and IL-6 in myofibroblasts (MFs) — lung cancer cell interactions, lung cancer cells (Lewis and CTM-167 cell lines) were stimulated by IL-6, MF-conditioned medium (MF-CM) or MFs, with or without TGF-β signaling inhibitor — SB431542 and/or JAK2/STAT3 inhibitor — JSI-124. MFs were stimulated by TGF-β, cancer cell-CM or cancer cells, with or without SB431542 and JSI-124. Cell proliferation, the levels of cytokines, expression of mRNA and protein were determined. Mice bearing xenograft tumors were intraperitoneally treated with SB431542 or JSI-124 and monitored for up to 45 days. In co-culture systems, MFs secreted high levels of IL-6, while cancer cells produced high levels of TGF-β. Recombinant IL-6 and MF-CM activated STAT3 and upregulated TGF-β in cancer cells. In contrast, cancer cell-CM or TGF-β stimulated MFs to produce IL-6. Blockade of JAK2/STAT3 and TGF-β signaling by specific inhibitors significantly inhibited cell proliferation in vitro and tumor growth in vivo of lung cancer cells. Our study demontrated that the TGF-β and IL-6/JAK2/STAT3 signaling pathways form a positive feedback signaling loop that mediated the interactions between MFs and lung cancer cells. Targeted inhibiton of this signaling loop could be a new approach for lung cancer prevention and therapy.

IL‐17A and IL‐17F single nucleotide polymorphisms associated with lung cancer in Chinese population

Genetic predisposition and environmental factors impact the development of lung cancer. The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) of the IL‐17A and IL‐17F genes with lung cancer risk in Chinese Han population.

Analysis of viral infection and biomarkers in patients with acute exacerbation of chronic obstructive pulmonary disease

To investigate viral infection in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Shanghai, and to analyze the clinical characteristics and biomarkers in viral infection.

The first patient recovered from avian influenza A H7N9 viral infection: A case report and review of the literature.

In March 2013, a novel avian-origin influenza A (H7N9) virus was isolated from throat swabs of 2 patients at the Fifth Peoples Hospital of Shanghai, China. Subsequently, 4 more patients infected by H7N9 were identified. Of the 6 patients, 4 died of acute respiratory distress syndrome. Here, we report the first case of a patient who recovered from pneumonia induced by H7N9 infection. The patient presented with fever, cough, and blood in sputum. Laboratory tests showed a low level of leukocytes, hypoxaemia, and increased levels of creatine kinase and lactate dehydrogenase. Imaging showed multiple areas of segmental ground-glass opacity in the right lung. Oseltamivir and antibiotics were administered. Supplemental oxygen helped relieve symptoms. Approximately 2 weeks after treatment, the patient finally recovered. A follow-up chest computed tomography scan taken 8 weeks later revealed that the ground-glass opacity was clearly absorbed. Therefore, timely intervention with oseltamivir and supplemental oxygen may be very important in the treatment of H7N9 infection.