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1.  Epidemiological and viral genome characteristics of the first human H7N9 influenza infection in Guangdong Province, China 
Journal of Thoracic Disease  2014;6(12):1785-1793.
The first H7N9 human case in south of China was confirmed in Guangdong Province on August 2013, outside of the typical influenza season. For investigating the H7N9 virus source and transmission in the local community, we analyze the epidemiology and genome features of the virus isolated from the first human infection detected in Guangdong Province.
The data including medical records, exposure history and time line of events for the H7N9 patient and close contacts was collected. Variation and genetic signatures of H7N9 virus in Guangdong was analyzed using ClustalW algorithm and comparison with mutations associated with changes in biological characteristics of the virus.
The female patient had a history of poultry exposure, and she was transferred from a local primary hospital to an intensive care unit (ICU) upon deterioration. No additional cases were reported. Similar to previous infections with avian influenza A (H7N9) virus, the patient presented with both upper and lower respiratory tract symptoms. Respiratory failure progressed quickly, and the patient recovered 4 weeks after the onset of symptoms. Genome analysis of the virus indicated that the predicted antigen city and internal genes of the virus are similar to previously reported H7N9 viruses. The isolated virus is susceptible to neuraminidase (NA) inhibitors but resistant to adamantine. Although this virus contains some unique mutations that were only detected in avian or environment-origin avian influenza A (H7N9) viruses, it is still quite similar to other human H7N9 isolates.
The epidemiological features and genome of the first H7N9 virus in Guangdong Province are similar to other human H7N9 infections. This virus may have existed in the environment and live poultry locally; therefore, it is important to be alert of the risk of H7N9 re-emergence in China, including emergence outside the typical influenza season.
PMCID: PMC4283329  PMID: 25589974
Avian influenza virus; epidemiology; H7N9; viral genome
2.  Visualization of Peripheral Pulmonary Artery Red Thrombi Utilizing Optical Coherence Tomography 
Korean Journal of Radiology  2013;14(5):854-858.
Optical coherence tomography (OCT) is a new imaging technique capable of obtaining high-resolution intravascular images and has been used in interventional cardiology. However, an application of OCT in pulmonary arteries had seldom been documented. In this case, OCT imaging is performed in peripheral pulmonary arteries and shows mural red thrombi. Subsequently, the red thrombi are aspirated and confirmed by a histological examination. These findings suggest that OCT may be a useful tool to depict peripheral pulmonary artery thrombi.
PMCID: PMC3772272  PMID: 24043986
Optical coherence tomography; Peripheral pulmonary artery thrombi; Pulmonary thromboembolism; CT pulmonary angiography; Intravascular ultrasound
3.  Capsaicin Cough Sensitivity and the Association with Clinical Parameters in Bronchiectasis 
PLoS ONE  2014;9(11):e113057.
Cough hypersensitivity has been common among respiratory diseases.
To determine associations of capsaicin cough sensitivity and clinical parameters in adults with clinically stable bronchiectasis.
We recruited 135 consecutive adult bronchiectasis patients and 22 healthy subjects. History inquiry, sputum culture, spirometry, chest high-resolution computed tomography (HRCT), Leicester Cough Questionnaire scoring, Bronchiectasis Severity Index (BSI) assessment and capsaicin inhalation challenge were performed. Cough sensitivity was measured as the capsaicin concentration eliciting at least 2 (C2) and 5 coughs (C5).
Despite significant overlap between healthy subjects and bronchiectasis patients, both C2 and C5 were significantly lower in the latter group (all P<0.01). Lower levels of C5 were associated with a longer duration of bronchiectasis symptoms, worse HRCT score, higher 24-hour sputum volume, BSI and sputum purulence score, and sputum culture positive for P. aeruginosa. Determinants associated with increased capsaicin cough sensitivity, defined as C5 being 62.5 µmol/L or less, encompassed female gender (OR: 3.25, 95%CI: 1.35–7.83, P<0.01), HRCT total score between 7–12 (OR: 2.57, 95%CI: 1.07–6.173, P = 0.04), BSI between 5–8 (OR: 4.05, 95%CI: 1.48–11.06, P<0.01) and 9 or greater (OR: 4.38, 95%CI: 1.48–12.93, P<0.01).
Capsaicin cough sensitivity is heightened in a subgroup of bronchiectasis patients and associated with the disease severity. Gender and disease severity, but not sputum purulence, are independent determinants of heightened capsaicin cough sensitivity. Current testing for cough sensitivity diagnosis may be limited because of overlap with healthy subjects but might provide an objective index for assessment of cough in future clinical trials.
PMCID: PMC4237391  PMID: 25409316
4.  Characterization of Lung Function Impairment in Adults with Bronchiectasis 
PLoS ONE  2014;9(11):e113373.
Characteristics of lung function impairment in bronchiectasis is not fully understood.
To determine the factors associated with lung function impairment and to compare changes in spirometry during bronchiectasis exacerbation and convalescence (1 week following 14-day antibiotic therapy).
We recruited 142 patients with steady-state bronchiectasis, of whom 44 with acute exacerbations in the follow-up were included in subgroup analyses. Baseline measurements consisted of chest high-resolution computed tomography (HRCT), sputum volume, purulence and bacteriology, spirometry and diffusing capacity. Spirometry, but not diffusing capacity, was examined during acute exacerbations and convalescence.
In the final multivariate models, having bronchiectasis symptoms for 10 years or greater (OR = 4.75, 95%CI: 1.46–15.43, P = 0.01), sputum culture positive for Pseudomonas aeruginosa (OR = 4.93, 95%CI: 1.52–15.94, P<0.01) and HRCT total score being 12 or greater (OR = 7.77, 95%CI: 3.21–18.79, P<0.01) were the major variables associated with FEV1 being 50%pred or less; and the only variable associated with reduced DLCO was 4 or more bronchiectatic lobes (OR = 5.91, 95%CI: 2.20–17.23, P<0.01). Overall differences in FVC and FEV1 during exacerbations and convalescence were significant (P<0.05), whereas changes in other spirometric parameters were less notable. This applied even when stratified by the magnitude of FEV1 and DLCO reduction at baseline.
Significant lung function impairment should raise alert of chest HRCT abnormality and sputum culture positive for Pseudomonas aeruginosa, in patients with predominantly mild to moderate steady-state bronchiectasis. Acute exacerbations elicited reductions in FVC and FEV1. Changes of other spirometric parameters were less significant during exacerbations.
Trial Registration NCT01761214
PMCID: PMC4236163  PMID: 25405614
5.  Compliance with severe sepsis bundles and its effect on patient outcomes of severe community-acquired pneumonia in a limited resources country 
Archives of Medical Science : AMS  2014;10(5):970-978.
Validation of compliance with severe sepsis bundles is still needed. The purpose of this study was to determine compliance and its outcomes in severe community-acquired pneumonia (CAP) patients in a limited resources country.
Material and methods
A prospective cohort study of 212 severe CAP patients was carried out. The implementation programme was organized into two continuous phases. The primary outcomes were compliance and hospital mortality.
Compliance with administration of antibiotics and vasopressors as well as plateau pressure on average < 30 cm H2O was high in both groups. In the bundles group, patients received more serum lactate monitoring (62.3% vs. 11.3%), more blood cultures (47.1% vs. 24.5%), more fluid resuscitation (63.2% vs. 26.4%) and volumes infused (1319.8 ±1107.4 ml vs. 461.9 ±799.3 ml), more inotropic dobutamine and/or packed red blood cells (21.7% vs. 10.0%), more low-dose steroids (56.5% vs. 15.0%), and more glucose control (51.9% vs. 6.6%) compared with such patients in the control group. The rates of total compliance with 6-hour, 24-hour, and 6/24-hour bundles in the prospective period were 47.1%, 51.9%, and 42.5%, respectively. Hospital mortality was reduced from 44.3% to 29.2% (p = 0.023) in the bundles group, and the compliant subgroup had a more than twofold decrease in mortality (17.8% vs. 37.7%, p = 0.003). Serum lactate measured, blood cultures, and fluid resuscitation showed independent relationships with decreased mortality.
Total compliance was relatively low, but the implementation of severe sepsis bundles could clearly reduce mortality from severe CAP.
PMCID: PMC4223141  PMID: 25395949
severe sepsis bundles; severe community-acquired pneumonia; severe sepsis; septic shock; compliance; mortality
6.  Macrolide Therapy in Adults and Children with Non-Cystic Fibrosis Bronchiectasis: A Systematic Review and Meta-Analysis 
PLoS ONE  2014;9(3):e90047.
A systematic review and meta-analysis was conducted to evaluate the efficacy and safety of macrolide therapy in adults and children with bronchiectasis.
We searched the PUBMED, EMBASE, CENTRAL databases to identify relevant studies. Two reviewers evaluated the studies and extracted data independently. The primary outcome was the number of bronchiectasis exacerbations. Secondary outcomes included exacerbation-related admissions, quality of life (QoL), spirometry, 6-minute walk test (6MWT) and adverse events.
Nine eligible trials with 559 participants were included. Six were conducted on adults, and the remaining on children. Macrolide therapy significantly reduced the number of patients experiencing one or more exacerbation in adults [risk ratio (RR) = 0.59; 95% CI, 0.40 to 0.86; P = 0.006; I2 = 65%] and children [RR = 0.86; 95% CI, 0.75–0.99; P = 0.04; I2 = 0%], but not the number of patients with admissions for exacerbation. Macrolide therapy was also associated with reduced frequency of exacerbations in adults (RR = 0.42; 95% CI, 0.29 to 0.61; P<0.001; I2 = 64%) and children (RR = 0.50; 95% CI, 0.35 to 0.71; P<0.001). Pooled analyses suggested that spirometry, including FEV1 and FVC, were significantly improved in adults but not in children. Macrolide therapy improved the QoL (WMD, −6.56; 95% CI, −11.99 to −1.12; P = 0.02; I2 = 86%) but no significant difference in 6MWT (WMD, 4.15; 95% CI, −11.83 to 20.13; P = 0.61; I2 = 31%) and the overall adverse events (RR, 0.96; 95% CI, 0.82 to 1.13; P = 0.66; I2 = 0%) in adults. However, reports of diarrhea and abdominal discomforts were higher with macrolide therapy.
Macrolide maintenance therapy, both in adults and children, was effective and safe in reducing bronchiectasis exacerbations, but not the admissions for exacerbations. In addition, macrolide administration in adults was associated with improvement in QoL and spirometry, but not 6WMT. Future studies are warranted to verify the optimal populations and clarify its potential effects on antimicrobial resistance.
PMCID: PMC3946068  PMID: 24603554
7.  Severe acute respiratory syndrome: a vanished evil? 
Journal of Thoracic Disease  2013;5(Suppl 2):S87-S89.
PMCID: PMC3747533  PMID: 23977440
8.  Comparison among nasopharyngeal swab, nasal wash, and oropharyngeal swab for respiratory virus detection in adults with acute pharyngitis 
BMC Infectious Diseases  2013;13:281.
Acute pharyngitis is frequently seen in primary care. Acute viral pharyngitis may be easily misdiagnosed as acute bacterial pharyngitis. Laboratory-confirmed diagnosis of respiratory viruses is recommended. The purpose of this study was to compare the sensitivities among oropharyngeal swab (OPS), nasopharyngeal swab (NPS), and nasal wash (NW) in adults with acute pharyngitis.
OPS, NPS, and NW were obtained from each participant with acute pharyngitis. The specimens were tested for 15 respiratory viruses by TaqMan real-time polymerase chain reaction. A sample was considered to be a true positive if any of the specimens was positive. The sensitivities among samples were compared by chi-square test or Fisher’s exact test, as appropriate.
One hundred three triple samples collected consecutively by OPS, NPS, and NW were obtained. In 73 patients, one or more viruses were detected by any of the three methods. Among all viruses, the sensitivity of NPS was significantly higher than that of NW (74% vs. 49%, respectively; p < 0.01) and OPS (74% vs. 49%, respectively; p < 0.01).
Flocked NPS collection may be the most effective alternative to NW and OPS for detection of respiratory viruses in adults with acute pharyngitis using TaqMan real-time polymerase chain reaction.
PMCID: PMC3698019  PMID: 23786598
Respiratory viruses; Acute pharyngitis; Oropharyngeal swab; Nasopharyngeal swab; Nasal wash; Sensitivity; TaqMan real-time polymerase chain reaction
9.  Responsiveness to leukotriene D4 and methacholine for predicting efficacy of montelukast in asthma 
Journal of Thoracic Disease  2013;5(3):298-301.
A lower responsiveness to leukotriene D4 (LTD4) or higher LTD4/[methacholine (MCh)] potency ratio might suggest preferable outcomes of short-term montelukast monotherapy in terms of airway inflammation and lung function in asthmatic patients.
PMCID: PMC3698267  PMID: 23825762
Asthma; leukotriene D4 (LTD4); leukotriene-responsive; leukotriene-unresponsive; methacholine (MCh); montelukast
10.  Prevalence of sensitization to weed pollens of Humulus scandens, Artemisia vulgaris, and Ambrosia artemisiifolia in northern China 
Objective: Weed pollens are common sources of allergens worldwide. The prevalence of weed pollen sensitization is not yet fully known in China. The purpose of this study was to investigate the prevalence of sensitization to weed allergens from Artemisia, Ambrosia, and Humulus in northern China. Methods: A total of 1 144 subjects (aged from 5 to 68 years) visiting our clinic from June to October 2011 underwent intradermal testing using a panel of 25 allergen sources. Subjects with positive skin responses to any pollen were further tested for their serum concentrations of IgE antibodies against Artemisia vulgaris, Ambrosia artemisiifolia, and Humulus scandens, and against the purified allergens, Art v 1 and Amb a 1. Results: Of 1 144 subjects, 170 had positive intradermal reactions to pollen and 144 donated serum for IgE testing. The prevalence of positive intradermal responses to pollens of Artemisia sieversiana, Artemisia annua, A. artemisiifolia, and H. scandens was 11.0%, 10.2%, 3.7%, and 6.6%, respectively. Among the intradermal positive subjects, the prevalence of specific IgE antigens to A. vulgaris was 58.3%, to A. artemisiifolia 14.7%, and to H. scandens 41.0%. The prevalence of specific IgE antigens to the allergen Art v 1 was 46.9%, and to Amb a 1 was 11.2%. The correlation between the presence of IgE antibodies specific to A. vulgaris and to the Art v 1 antigen was very high. Subjects with A. artemisiifolia specific IgE also had A. vulgaris specific IgE, but with relatively high levels of A. vulgaris IgE antibodies. There were no correlations between the presence of IgE antibodies to H. scandens and A. vulgaris or to H. scandens and A. artemisiifolia. Conclusions: The intradermal prevalence of weed pollen sensitization among allergic subjects in northern China is about 13.5%. Correlations of specific IgE antibodies suggest that pollen allergens from Artemisia and Humulus are independent sources for primary sensitization.
PMCID: PMC3596575  PMID: 23463767
Humulus scandens; Artemisia vulgaris; Ambrosia artemisiifolia; Intradermal test; Specific IgE; Sensitization
11.  Epidemic Plasmid Carrying blaCTX-M-15 in Klebsiella penumoniae in China 
PLoS ONE  2013;8(1):e52222.
To investigate the local epidemiology of Klebsiella penumoniae carrying blaCTX-M-15 in southern China and to characterize the genetic environment of blaCTX-M-15.
PCR and DNA sequencing were used to detect and characterize the genetic contexts of blaCTX-M-15. The clonal relatedness of isolates carrying blaCTX-M-15 was determined by pulse-field gel electrophoresis. Conjugative plasmids carrying blaCTX-M-15 were obtained by mating and were further subject to restriction analysis and replicon typing.
A total of 47CTX-M-15 ESBL-producing isolates of K. pneumoniae were collected from nine hospitals in China from October 2007 to October 2008. Isolates were clustered into various clonal groups. The local spread of blaCTX-M-15 was mainly mediated by one major conjugative plasmid as determined by S1-PFGE and restriction analysis. A 90-kb plasmid belonging to incompatible group FII was the major carrier of blaCTX-M-15 in K. pneumoniae. Except blaTEM-1, the resistance genes such as blaSHV, blaDHA-1, blaOXA-1, qnrB, qnrS, aac(3)-II, and aac(6′)-Ib were not found in the plasmid. In the comparing of conjugative gene sequence, it is 100% identical with the plasmid pKF3–94, which was found in K. pneumonia from Zhejiang province of china previously.
blaCTX-M-15 was prevalent in K. pneumonia of southern China. The dissemination of blaCTX-M-15 appeared to be due to the horizontal transfer of a 90-kb epidemic plasmid.
PMCID: PMC3558504  PMID: 23382815
12.  Strengths and Weaknesses of Immunotherapy for Advanced Non-Small-Cell Lung Cancer: A Meta-Analysis of 12 Randomized Controlled Trials 
PLoS ONE  2012;7(3):e32695.
Lung cancer is one of the leading causes of cancer death worldwide. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Immunotherapy has yielded no consistent benefit to date for those patients. Assessing the objective efficacy and safety of immunotherapy for advanced NSCLC patients will help to instruct the future development of immunotherapeutic drugs.
Methodology and Principal Findings
We performed a meta-analysis of 12 randomized controlled trials including 3134 patients (1570 patients in the immunotherapy group and 1564 patients in the control group) with histologically confirmed stage IIIA, IIIB, or IV NSCLC. The analysis was executed with efficacy end points regarding overall survival (OS), progression-free survival (PFS), complete response (CR), partial response (PR), and total effective rate. Overall unstratified OS, PFS, PR, and total effective rate were significantly improved in advanced NSCLC patients in the immunotherapy group (P = 0.0007, 0.0004, 0.002, 0.003, respectively), whereas CR was not improved (P = 0.97). Subgroup analysis showed that monoclonal antibody (mAb) immunotherapy significantly improved the PFS, PR, and total effective rate and showed a trend of improving OS of advanced NSCLC patients compared with the control group, with one kind of adverse event being significantly dominant. Compared with the control group, the vaccine subgroup showed no significant difference with regard to serious adverse events, whereas cytokine immunotherapy significantly induced three kinds of serious adverse events.
Immunotherapy works efficiently on advanced NSCLC patients. Of several immunotherapies, mAb therapy may be a potential immunotherapy for advanced NSCLC patients, and become a standard complementary therapeutic approach in the future if the issues concerning toxicity and allergenicity of mAbs have been overcome.
PMCID: PMC3293858  PMID: 22403699
14.  Establishment and characterization of a new drug surviving cell line Am1010, derived directly from muscle metastases of a human lung adenocarcinoma patient with multi-drug-resistance to cisplatin, taxol, and gefitinib 
Acta Pharmacologica Sinica  2010;31(5):601-608.
To Characterize a new human lung cancer cell line Am1010, derived from drug-surviving cells (DSCs).
The Am1010 cell line was established after 4 cycles of chemotherapy from an arm muscle metastasic tumor of a patient diagnosed with lung adenocarcinoma. The cell line has been remained in continuous culture for more than one year during this study.
The Am1010 cell line demonstrated in vitro multi-drug-resistance to cisplatin, taxol, and gefitinib. The Am1010 cell doubling time without drug treatment was 42.395 h. The IC50 value of cisplatin was 4.299 μmol/L and >10 μmol/L for the Am1010 and P0318 (a cell line derived from non-DSCs) cells, respectively. The IC50 value of taxol was 0.067 μmol/L and >1 μmol/L for the Am1010 and P0318 cells, respectively. The IC50 value of gefitinib was 15.233 μmol/L and >70 μmol/L for Am1010 and P0318 cells, respectively. 11 genes involved in the focal adhesion and cell adhesion pathways were found to be differentially expressed. The cells of Am1010 have a significantly larger chromosome number than most lung cancer cell lines.
This novel DSCs derived lung cancer cell line will be a valuable in vitro tool for the investigation of lung cancer drug resistance and metastasis.
PMCID: PMC4002755  PMID: 20418894
lung adenocarcinoma; Am1010; multi-drug-resistance; metastases; drug surviving cells; focal and cell adhesion
15.  Prevalence of asthma among Chinese adolescents living in Canada and in China 
Studies of the prevalence of asthma among migrating populations may help in identifying environmental risk factors.
We analyzed data from Vancouver, Canada, and from Guangzhou, Beijing and Hong Kong, China, collected during phase 3 of the International Study of Asthma and Allergies in Childhood. We subdivided the Vancouver adolescents according to whether they were Chinese immigrants to Canada, Canadian-born Chinese or Canadian-born non-Chinese. We compared the prevalence of asthma and wheezing among Chinese adolescents born in Canada, Chinese adolescents who had immigrated to Canada and Chinese adolescents living in China.
Of 7794 Chinese adolescents who met the inclusion criteria, 3058 were from Guangzhou, 2824 were from Beijing, and 1912 were from Hong Kong. Of 2235 adolescents in Vancouver, Canada, 475 were Chinese immigrants, 617 were Canadian-born Chinese, and 1143 were Canadian-born non-Chinese. The prevalence of current wheezing among boys ranged from 5.9% in Guangzhou to 11.2% in Canadian-born Chinese adolescents. For girls, the range was 4.3% in Guangzhou to 9.8% in Canadian-born Chinese adolescents. The prevalence of ever having had asthma ranged from 6.6% to 16.6% for boys and from 2.9% to 15.0% for girls. Prevalence gradients persisted after adjustment for other environmental variables (odds ratios for ever having had asthma among Canadian-born Chinese compared with native Chinese in Guangzhou: 2.72 [95% confidence interval 1.75–4.23] for boys and 5.50 [95% confidence interval 3.21–9.44] for girls; p < 0.001 for both). Among Chinese adolescents living in Vancouver, the prevalence of ever wheezing increased with duration of residence, from 14.5% among those living in Canada for less than 7 years to 20.9% among those living their entire life in Canada. The same pattern was observed for the prevalence of ever having had asthma, from 7.7% to 15.9%.
Asthma symptoms in Chinese adolescents were lowest among residents of mainland China, were greater for those in Hong Kong and those who had immigrated to Canada, and were highest among those born in Canada. These findings suggest that environmental factors and duration of exposure influence asthma prevalence.
PMCID: PMC2582762  PMID: 19015564

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