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1.
Background
Lung ultrasonography has been advocated in diagnosing pediatric community-acquired pneumonia. However, its function in identifying necrotizing pneumonia, a complication, has not been explored. This study investigated the value of lung ultrasonography in diagnosing pediatric necrotizing pneumonia and its role in predicting clinical outcomes.Methods
We retrospectively reviewed 236 children with community-acquired pneumonia who were evaluated using lung ultrasonography within 2–3 days after admission. The ultrasonographic features assessed included lung perfusion, the presence of hypoechoic lesions, and the amount of pleural effusion. Chest computed tomography was also performed in 96 patients as clinically indicated. Detailed records of clinical information were obtained.Results
Our results showed a high correlation between the degree of impaired perfusion in ultrasonography and the severity of necrosis in computed tomography (r = 0.704). The degree of impaired perfusion can favorably be used to predict massive necrosis in computed tomography (area under the receiver operating characteristic curve, 0.908). The characteristics of impaired perfusion and hypoechoic lesions in ultrasonography were associated with an increased risk of pneumatocele formation (odds ratio (OR), 10.11; 95% CI, 2.95–34.64) and the subsequent requirement for surgical lung resection (OR, 8.28; 95% CI, 1.86–36.93). Furthermore, a longer hospital stay would be expected if moderate-to-massive pleural effusion was observed in addition to impaired perfusion in ultrasonography (OR, 3.08; 95% CI, 1.15–8.29).Conclusion
Lung ultrasonography is favorably correlated with chest computed tomography in the diagnosis of necrotizing pneumonia, especially regarding massive necrosis of the lung. Because it is a simple and reliable imaging tool that is valuable in predicting clinical outcomes, we suggest that ultrasonography be applied as a surrogate for computed tomography for the early detection of severe necrotizing pneumonia in children. 相似文献2.
Libing Jiang Yuefeng Ma Changwei Zhao Weifeng Shen Xia Feng Yongan Xu Mao Zhang 《PloS one》2015,10(6)
Background
Pulmonary embolism (PE) is a potentially life-threatening condition. Although computed tomography pulmonary angiography (CTPA) is the reference standard for diagnosis, its early diagnosis remains a challenge, and the concerns about the radiation exposures further limit the general use of CTPA. The primary aim of this meta-analysis was to evaluate the overall diagnostic accuracy of transthoracic lung ultrasound (TLS) in the diagnosis of PE.Methods
PubMed, Web of science, OvidSP, ProQuest, EBSCO, Cochrane Library and Clinicaltrial.gov were searched systematically. The quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and hierarchical summary receiver operating characteristic (HSROC) curves were used to examine the TS performance. The Bayes analysis was used to calculate the post-test probability of PE. Publication bias was assessed with Deeks funnel plot.Results
The results indicated that the sensitivity, specificity, PLR and NLR were 0.85 (95% confidence interval (CI), 0.78 to 0.90), and 0.83 (95% CI, 0.73 to 0.90). And the DOR and HSROC were 28.82 (95% CI, 17.60 to 47.21), 0.91(95% CI, 0.88, 0.93).Conclusions
The present meta-analysis suggested that transthoracic lung ultrasonography is helpful in diagnosing pulmonary embolism. Although the application of transthoracic lung ultrasound may change some patients’ diagnostic processes, it is inappropriate to generally use transthoracic ultrasonography in diagnosing pulmonary embolism currently. 相似文献3.
Allison A. Lambert Jennifer O. Lam Julie J. Paik Cesar Ugarte-Gil M. Bradley Drummond Trevor A. Crowell 《PloS one》2015,10(6)
Background
Proton-pump inhibitors (PPIs) are among the most frequently prescribed medications. Community-acquired pneumonia (CAP) is a common cause of morbidity, mortality and healthcare spending. Some studies suggest an increased risk of CAP among PPI users. We conducted a systematic review and meta-analysis to determine the association between outpatient PPI therapy and risk of CAP in adults.Methods
We conducted systematic searches of MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, Scopus and Web of Science on February 3, 2014. Case-control studies, case-crossover, cohort studies and randomized controlled trials reporting outpatient PPI exposure and CAP diagnosis for patients ≥18 years old were eligible. Our primary outcome was the association between CAP and PPI therapy. A secondary outcome examined the risk of hospitalization for CAP and subgroup analyses evaluated the association between PPI use and CAP among patients of different age groups, by different PPI doses, and by different durations of PPI therapy.Results
Systematic review of 33 studies was performed, of which 26 studies were included in the meta-analysis. These 26 studies included 226,769 cases of CAP among 6,351,656 participants. We observed a pooled risk of CAP with ambulatory PPI therapy of 1.49 (95% CI 1.16, 1.92; I2 99.2%). This risk was increased during the first month of therapy (OR 2.10; 95% CI 1.39, 3.16), regardless of PPI dose or patient age. PPI therapy also increased risk for hospitalization for CAP (OR 1.61; 95% CI: 1.12, 2.31).Discussion
Outpatient PPI use is associated with a 1.5-fold increased risk of CAP, with the highest risk within the first 30 days after initiation of therapy. Providers should be aware of this risk when considering PPI use, especially in cases where alternative regimens may be available or the benefits of PPI use are uncertain. 相似文献4.
Mohamed A. Elemraid Michelle Muller David A. Spencer Stephen P. Rushton Russell Gorton Matthew F. Thomas Katherine M. Eastham Fiona Hampton Andrew R. Gennery Julia E. Clark 《PloS one》2014,9(8)
Introduction
World Health Organization (WHO) radiological classification remains an important entry criterion in epidemiological studies of pneumonia in children. We report inter-observer variability in the interpretation of 169 chest radiographs in children suspected of having pneumonia.Methods
An 18-month prospective aetiological study of pneumonia was undertaken in Northern England. Chest radiographs were performed on eligible children aged ≤16 years with clinical features of pneumonia. The initial radiology report was compared with a subsequent assessment by a consultant cardiothoracic radiologist. Chest radiographic changes were categorised according to the WHO classification.Results
There was significant disagreement (22%) between the first and second reports (kappa = 0.70, P<0.001), notably in those aged <5 years (26%, kappa = 0.66, P<0.001). The most frequent sources of disagreement were the reporting of patchy and perihilar changes.Conclusion
This substantial inter-observer variability highlights the need for experts from different countries to create a consensus to review the radiological definition of pneumonia in children. 相似文献5.
Background
The benefit of corticosteroids in community-acquired pneumonia (CAP) remains controversial. We did a meta-analysis to include all the randomized controlled trials (RCTs) which used corticosteroids as adjunctive therapy, to examine the benefits and risks of corticosteroids in the treatment of CAP in adults.Methods
Databases including Pubmed, EMBASE, the Cochrane controlled trials register, and Google Scholar were searched to find relevant trials. Randomized and quasi-randomized trials of corticosteroids treatment in adult patients with CAP were included. Effects on primary outcome (mortality) and secondary outcomes (adverse events) were accessed in this meta-analysis.Results
Nine trials involving 1001 patients were included. Use of corticosteroids did not significantly reduce mortality (Peto odds ratio [OR] 0.62, 95% confidence interval [CI] 0.37–1.04; P = 0.07). In the subgroup analysis by the severity, a survival benefit was found among severe CAP patients (Peto OR 0.26, 95% CI 0.11–0.64; P = 0.003). In subgroup analysis by duration of corticosteroids treatment, significant reduced mortality was found among patients with prolonged corticosteroids treatment (Peto OR 0.51, 95% CI 0.26–0.97; P = 0.04; I 2 = 37%). Corticosteroids increased the risk of hyperglycemia (Peto OR 2.64, 95% CI 1.68–4.15; P<0.0001), but without increasing the risk of gastroduodenal bleeding (Peto OR 1.67, 95% CI 0.41–6.80; P = 0.47) and superinfection (Peto OR 1.36, 95% CI 0.65–2.84; P = 0.41).Conclusion
Results from this meta-analysis did not suggest a benefit for corticosteroids treatment in patients with CAP. However, the use of corticosteroids was associated with improved mortality in severe CAP. In addition, prolonged corticosteroids therapy suggested a beneficial effect on mortality. These results should be confirmed by future adequately powered randomized trials. 相似文献6.
目的:探索肺超声(LUS)在获得性肺炎(CAP)患儿诊断中的临床应用价值。方法:选取自2013年4月至2014年11月我院确诊为CAP的患儿95例,以腋前线、腋后线为界,将患儿肺脏分为前、后、侧三个区域,对所有患儿进行LUS检查,观察胸膜线、B线、肺实变程度及胸腔积液,并对支气管充气征进行检查。结果:95例CAP患儿经LUS检查后,诊断为阳性的有93例,阴性有2例,准确率为97.89%;CAP患儿的LUS的主要表现为肺泡-间质综合征、支气管充气症、胸膜线异常、胸腔积液;80例为综合表现(84.21%),15例为单一表现(15.79%)。结论:LUS诊断CAP患儿具有较高的准确率,结果安全可靠,可以应用于为临床诊断CAP。 相似文献
7.
Kuan-Fu Chen Chung-Hsien Chaou Jing-Yi Jiang Hsueh-Wen Yu Yu-Hsiang Meng Wei-Chen Tang Chin-Chieh Wu 《PloS one》2016,11(4)
IntroductionLipopolysaccharide-binding protein (LBP) is widely reported as a biomarker to differentiate infected from non-infected patients. The diagnostic use of LBP for sepsis remains a matter of debate. We aimed to perform a systematic review and meta-analysis to assess the diagnostic accuracy of serum LBP for sepsis in adult patients.MethodsWe performed a systematic review and meta-analysis to assess the accuracy of LBP for sepsis diagnosis. A systematic search in PubMed and EMBASE for studies that evaluated the diagnostic role of LBP for sepsis through December 2015 was conducted. We searched these databases for original, English language, research articles that studied the diagnostic accuracy between septic and non-septic adult patients. Sensitivity, specificity, and other measures of accuracy, such as diagnostic odds ratio (DOR) and area under the receiver operating characteristic curve (AUC) of LBP were pooled using the Hierarchical Summary Receiver Operating Characteristic (HSROC) method.ResultsOur search returned 53 reports, of which 8 fulfilled the inclusion criteria, accounting for 1684 patients. The pooled sensitivity and specificity of LBP for diagnosis of sepsis by the HSROC method were 0.64 (95% CI: 0.56–0.72) and 0.63 (95% CI: 0.53–0.73), respectively. The value of the DOR was 3.0 (95% CI: 2.0–4.0) and the AUC was 0.68 (95% CI: 0.64–0.72). Meta-regression analysis revealed that cut-off values accounted for the heterogeneity of sensitivity and sample size (> = 150) accounted for the heterogeneity of specificity.ConclusionsBased on the results of our meta-analysis, LBP had weak sensitivity and specificity in the detection of sepsis. LBP may not be practically recommended for clinical utilization as a single biomarker. 相似文献
8.
Background
Non-cardiovascular chest pain (NCCP) leads to impaired quality of life and is associated with a high disease burden. Upon ruling out cardiovascular disease, only vague recommendations exist for further treatment.Objectives
To summarize treatment efficacy for patients presenting with NCCP.Methods
Systematic review and meta-analysis. In July 2013, Medline, Web of Knowledge, Embase, EBSCOhost, Cochrane Reviews and Trials, and Scopus were searched. Hand and bibliography searches were also conducted. Randomized controlled trials (RCTs) evaluating non-surgical treatments in patients with NCCP were included. Exclusion criteria were poor study quality and small sample size (<10 patients per group).Results
Thirty eligible RCT’s were included. Most studies assessed PPI efficacy for gastroesophageal reflux disorders (GERD, n = 10). Two RCTs included musculoskeletal chest pain, seven psychotropic drugs, and eleven various psychological interventions. Study quality was high in five RCTs and acceptable in 25. PPI treatment in patients with GERD (5 RCTs, 192 patients) was more effective than placebo [pooled OR 11.7 (95% CI 5.5 to 25.0, heterogeneity I2 = 6.1%)]. The pooled OR in GERD negative patients (4 RCTs, 156 patients) was 0.8 (95% CI 0.2 to 2.8, heterogeneity I2 = 50.4%). In musculoskeletal NCCP (2 RCTs, 229 patients) manual therapy was more effective than usual care but not than home exercise [pooled mean difference 0.5 (95% CI −0.3 to 1.3, heterogeneity I2 = 46.2%)]. The findings for cognitive behavioral treatment, serotonin reuptake inhibitors, tricyclic antidepressants were mixed. Most evidence was available for cognitive behavioral treatment interventions.Limitations
Only a small number of studies were available.Conclusions
Timely diagnostic evaluation and treatment of the disease underlying NCCP is important. For patients with suspected GERD, high-dose treatment with PPI is effective. Only limited evidence was available for most prevalent diseases manifesting with chest pain. In patients with idiopathic NCCP, treatments based on cognitive behavioral principles might be considered. 相似文献9.
Christophe Marti Olivier Grosgurin Stephan Harbarth Christophe Combescure Mohamed Abbas Olivier Rutschmann Arnaud Perrier Nicolas Garin 《PloS one》2015,10(12)
Background
Community-acquired pneumonia (CAP) induces lung and systemic inflammation, leading to high morbidity and mortality. We systematically reviewed the risks and benefits of adjunctive corticotherapy in the management of patients with CAP.Methods
We systematically searched Pubmed, Embase and the Cochrane Library for randomized controlled trials comparing adjunctive corticotherapy and antimicrobial therapy with antimicrobial therapy alone in patients with CAP. The primary outcome was 30-day mortality. Secondary outcomes were length of hospital stay, time to clinical stability and severe complications.Results
14 trials (2077 patients) were included. The reported 30-day mortality was 7.9% (80/1018) among patients treated with adjunctive corticotherapy versus 8.3% (85/1028) among patients treated with antimicrobial therapy alone (RR 0.84; 95%CI 0.55 to1.29). Adjunctive corticotherapy was associated with a reduction of severe complications (RR 0.36; 95%CI 0.23 to 0.56), a shorter length of stay (9.0 days; 95%CI 7.6 to 10.7 vs 10.6 days; 95%CI 7.4 to 15.3) and a shorter time to clinical stability (3.3 days; 95% CI 2.8 to 4.1 vs 4.3 days; 95%CI 3.6 to 5.1). The risk of hyperglycemia was higher among patients treated with adjunctive corticotherapy (RR 1.59; 95%CI 1.06 to 2.38), whereas the risk of gastro-intestinal bleeding was similar (RR 0.83; 95%CI 0.35 to 1.93). In the subgroup analysis based on CAP severity, a survival benefit was found among patients with severe CAP (RR 0.47; 95%CI 0.23 to 0.96).Conclusion
Adjunctive corticotherapy is associated with a reduction of length of stay, time to clinical stability, and severe complications among patients with CAP, but the effect on mortality remains uncertain. 相似文献10.
Backgroundi-Scan is a novel virtual chromoendoscopy system designed to enhance surface and vascular patterns to improve optical diagnostic performance. Numerous prospective studies have been done to evaluate the accuracy of i-Scan in differentiating colonic neoplasms from non-neoplasms. i-Scan could be an effective endoscopic technique for optical diagnosis of colonic polyps.ObjectiveOur aim of this study was to perform a meta-analysis of published data to establish the diagnostic accuracy of i-Scan for optical diagnosis of colonic polyps.MethodsWe searched PubMed, Medline, Elsevier ScienceDirect and Cochrane Library databases. We used a bivariate meta-analysis following a random effects model to summarize the data and plotted hierarchical summary receiver-operating characteristic (HSROC) curves. The area under the HSROC curve (AUC) serves as an indicator of the diagnostic accuracy.ResultsThe meta-analysis included a total of 925 patients and 2312 polyps. For the overall studies, the area under the HSROC curve was 0.96. The summary sensitivity was 90.4% (95%CI 85%-94.1%) and specificity was 90.9% (95%CI 84.3%-94.9%). In 11 studies predicting polyps histology in real-time, the summary sensitivity and specificity was 91.5% (95%CI 85.7%-95.1%) and 92.1% (95%CI 84.5%-96.1%), respectively, with the AUC of 0.97. For three different diagnostic criteria (Kudo, NICE, others), the sensitivity was 86.3%, 93.0%, 85.0%, respectively and specificity was 84.8%, 94.4%, 91.8%, respectively.ConclusionsEndoscopic diagnosis with i-Scan has accurate optical diagnostic performance to differentiate neoplastic from non-neoplastic polyps with an area under the HSROC curve exceeding 0.90. Both the sensitivity and specificity for diagnosing colonic polyps are over 90%. 相似文献
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Introduction
Subjective memory complaints are common with aging. Docosahexaenoic acid (DHA; 22:6 n-3) is a long-chain polyunsaturated fatty acid (LCPUFA) and an integral part of neural membrane phospholipids that impacts brain structure and function. Past research demonstrates a positive association between DHA plasma status/dietary intake and cognitive function.Objectives
The current meta-analysis was designed to determine the effect of DHA intake, alone or combined with eicosapentaenoic acid (EPA; 20:5 n-3), on specific memory domains: episodic, working, and semantic in healthy adults aged 18 years and older. A secondary objective was to systematically review/summarize the related observational epidemiologic literature.Methods
A systematic literature search of clinical trials and observational studies that examined the relationship between n-3 LCPUFA on memory outcomes in healthy adults was conducted in Ovid MEDLINE and EMBASE databases. Studies of subjects free of neurologic disease at baseline, with or without mild memory complaints (MMC), were included. Random effects meta-analyses were conducted to generate weighted group mean differences, standardized weighted group mean differences (Hedge’s g), z-scores, and p-values for heterogeneity comparing DHA/EPA to a placebo. A priori sub-group analyses were conducted to evaluate the effect of age at enrollment, dose level, and memory type tested.Results
Episodic memory outcomes of adults with MMC were significantly (P<.004) improved with DHA/EPA supplementation. Regardless of cognitive status at baseline, > 1 g/day DHA/EPA improved episodic memory (P<.04). Semantic and working memory changes from baseline were significant with DHA but no between group differences were detected. Observational studies support a beneficial association between intake/blood levels of DHA/EPA and memory function in older adults.Conclusion
DHA, alone or combined with EPA, contributes to improved memory function in older adults with mild memory complaints. 相似文献14.
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Background
Ventilator-associated pneumonia (VAP) is considered to be a worldwide issue along with the development of supportive ventilation. The preventing strategy is of great importance for its poor prognostic and difficulties in treatment. Probiotics have been advocated as one of the possible preventive measures. We conducted a systematic review and meta-analysis to explore the potential benefits of probiotics.Methods
The databases, Web of science, PubMed, Ovid and Cochrane lib were searched for randomized controlled trials (RCTs) publications that compared the effectiveness of probiotics with placebo in the prevention of VAP. The incidence of VAP was considered as the primary endpoint, mortality, length of stay in intensive care units (ICUs), etiology of the infections were considered as secondary endpoints.Results
A total of 844 patients from 5 trials were subjected to meta-analysis. Probiotics did not significantly decrease the incidence of VAP (RR 0.94, 95%CI 0.85-1.04, p=0.22), however, the administration of probiotics reduced the risk of VAP caused by Pseudomonas aeruginosa (P. aeruginosa) (RR 0.30, 95%CI 0.11-0.91, P=0.03). It failed to affect any other endpoints.Conclusion
Probiotic prophylaxis of ventilator-associated pneumonia remained inconclusive and it failed to improve the prognosis of general mechanically ventilated patients. It was noteworthy that infections caused by P. aeruginosa was reduced by administration of probiotics. In further, it is recommended that advanced studies should exploit transformation in pathogenic microorganisms owing to administration of probiotics as well as the specific population. 相似文献17.
Objective
To evaluate the application of the Ologen implant compared to mitomycin C (MMC) on the outcome of trabeculectomy and to examine the balance of risks and benefits.Methods
A systematic literature search (Pubmed, Embase, the Cochrane Library, and the Chinese Biomedicine Database) was performed. Randomized controlled trials comparing the Ologen implant with MMC in trabeculectomy were selected. The efficacy measures were the weighted mean differences (WMDs) for the intraocular pressure reduction (IOPR), the reduction in glaucoma medications, and the relative risks (RRs) for success rates. The tolerability measures were RRs for adverse events. The pooled effects were calculated using the random-effects model.Results
Seven randomized controlled trials including 227 eyes were included in this meta-analysis. The WMDs of the IOPR comparing the Ologen group with the MMC group were −2.98 (95% Cl: −5.07 to −0.89) at one month, −1.41 (−3.72 to 0.91) at three months, −1.69 (−3.68 to 0.30) at six months, −1.94 (−3.88 to 0.01) at 12 months, and 0.65 (−2.17 to 0.47) at 24 months. There was no statistically significance except at one and 12 months after surgery. No significant difference in the reduction in glaucoma medications or complete and qualified success rates were found. The rates of adverse events also did not differ significantly between Ologen and MMC.Conclusions
The Ologen implant is comparable with MMC for trabeculectomy in IOP-lowering efficacy, reduction in the number of glaucoma medications, success rates, and tolerability. However, the results should be interpreted cautiously since relevant evidence is still limited, although it is accumulating. Further large-scale, well-designed randomized controlled trials are urgently needed. 相似文献18.
Anne-Sophie Riteau Mikael Tassin Guillemette Chambon Claudine Le Vaillant Jocelyne de Laveaucoupet Marie-Pierre Quéré Madeleine Joubert Sophie Prevot Henri-Jean Philippe Alexandra Benachi 《PloS one》2014,9(4)
Purpose
To evaluate the accuracy of ultrasonography and magnetic resonance imaging (MRI) in the diagnosis of placenta accreta and to define the most relevant specific ultrasound and MRI features that may predict placental invasion.Material and Methods
This study was approved by the institutional review board of the French College of Obstetricians and Gynecologists. We retrospectively reviewed the medical records of all patients referred for suspected placenta accreta to two university hospitals from 01/2001 to 05/2012. Our study population included 42 pregnant women who had been investigated by both ultrasonography and MRI. Ultrasound images and MRI were blindly reassessed for each case by 2 raters in order to score features that predict abnormal placental invasion.Results
Sensitivity in the diagnosis of placenta accreta was 100% with ultrasound and 76.9% for MRI (P = 0.03). Specificity was 37.5% with ultrasonography and 50% for MRI (P = 0.6). The features of greatest sensitivity on ultrasonography were intraplacental lacunae and loss of the normal retroplacental clear space. Increased vascularization in the uterine serosa-bladder wall interface and vascularization perpendicular to the uterine wall had the best positive predictive value (92%). At MRI, uterine bulging had the best positive predictive value (85%) and its combination with the presence of dark intraplacental bands on T2-weighted images improved the predictive value to 90%.Conclusion
Ultrasound imaging is the mainstay of screening for placenta accreta. MRI appears to be complementary to ultrasonography, especially when there are few ultrasound signs. 相似文献19.
Objective
This systematic review and meta-analysis aimed to evaluate the overall survival, local recurrence, distant metastasis, and complications of mediastinal lymph node dissection (MLND) versus mediastinal lymph node sampling (MLNS) in stage I–IIIA non-small cell lung cancer (NSCLC) patients.Methods
A systematic search of published literature was conducted using the main databases (MEDLINE, PubMed, EMBASE, and Cochrane databases) to identify relevant randomized controlled trials that compared MLND vs. MLNS in NSCLC patients. Methodological quality of included randomized controlled trials was assessed according to the criteria from the Cochrane Handbook for Systematic Review of Interventions (Version 5.1.0). Meta-analysis was performed using The Cochrane Collaboration’s Review Manager 5.3. The results of the meta-analysis were expressed as hazard ratio (HR) or risk ratio (RR), with their corresponding 95% confidence interval (CI).Results
We included results reported from six randomized controlled trials, with a total of 1,791 patients included in the primary meta-analysis. Compared to MLNS in NSCLC patients, there was no statistically significant difference in MLND on overall survival (HR = 0.77, 95% CI 0.55 to 1.08; P = 0.13). In addition, the results indicated that local recurrence rate (RR = 0.93, 95% CI 0.68 to 1.28; P = 0.67), distant metastasis rate (RR = 0.88, 95% CI 0.74 to 1.04; P = 0.15), and total complications rate (RR = 1.10, 95% CI 0.67 to 1.79; P = 0.72) were similar, no significant difference found between the two groups.Conclusions
Results for overall survival, local recurrence rate, and distant metastasis rate were similar between MLND and MLNS in early stage NSCLC patients. There was no evidence that MLND increased complications compared with MLNS. Whether or not MLND is superior to MLNS for stage II–IIIA remains to be determined. 相似文献20.
Zhenjie Wu Mingmin Li Bing Liu Chen Cai Huamao Ye Chen Lv Qing Yang Jing Sheng Shangqing Song Le Qu Liang Xiao Yinghao Sun Linhui Wang 《PloS one》2014,9(4)