Radiomic Analysis of Contrast-Enhanced CT Predicts Glypican 3-Positive Hepatocellular Carcinoma.

BACKGROUND: The Glypican 3 (GPC3)-positive expression in Hepatocellular Carcinoma (HCC) is associated with a worse prognosis. Moreover, GPC3 has emerged as an immunotherapeutic target in advanced unresectable HCC systemic therapy. It is significant to diagnose GPC3-positive HCCs before therapy. Regarding imaging diagnosis of HCC, dynamic contrast-enhanced CT is more common than MRI in many regions. OBJECTIVE: The aim of this study was to construct and validate a radiomics model based on contrast-enhanced CT to predict the GPC3 expression in hepatocellular carcinoma. METHODS: This retrospective study included 141 (training cohort: n = 100; validation cohort: n = 41) pathologically confirmed HCC patients. Radiomics features were extracted from the Artery Phase (AP) images of contrast-enhanced CT. Logistic regression with the Least Absolute Shrinkage and Selection Operator (LASSO) regularization was used to select features to construct radiomics score (Rad-score). A final combined model, including the Rad-score of the selected features and clinical risk factors, was established. Receiver Operating Characteristic (ROC) curve analysis, Delong test, and Decision Curve Analysis (DCA) were used to assess the predictive performance of the clinical and radiomics models. RESULTS: 5 features were selected to construct the AP radiomics model of contrast-enhanced CT. The radiomics model of AP from contrast-enhanced CT was superior to the clinical model of AFP in training cohorts (P < 0.001), but not superior to the clinical model in validation cohorts (P = 0.151). The combined model (AUC = 0.867 vs. 0.895), including AP Rad-score and serum Alpha-Fetoprotein (AFP) levels, improved the predictive performance more than the AFP model (AUC = 0.651 vs. 0.718) in the training and validation cohorts. The combined model, with a higher decision curve indicating more net benefit, exhibited a better predictive performance than the AP radiomics model. DCA revealed that at a range threshold probability approximately above 60%, the combined model added more net benefit compared to the AP radiomics model of contrastenhanced CT. CONCLUSION: A combined model including AP Rad-score and serum AFP levels based on contrast-enhanced CT could preoperatively predict GPC3-positive expression in HCC.

Long non-coding RNA ATB expedites non-small cell lung cancer progression by the miR-200b/fibronectin 1 axis.

BACKGROUND: Long non-coding RNA (lncRNA) ATB belongs to an active modulator in multiple cancers, but its expression along with potential underlying non-small cell lung cancer (NSCLC) is obscure. Our study aimed to investigate the role and potential mechanism of LncRNA ATB in NSCLC. METHODS: LncRNA ATB expression in NSCLC tissues and cell lines was detected by qRT-PCR. Effects of LncRNA ATB on NSCLC cell proliferation, migration and invasion were assessed by MTS, colony formation and transwell assays. The connection among LncRNA ATB, miR-200b and fibronectin 1 (FN1) was determined by bioformatics prediction and luciferase reporter assay. RESULTS: In this research, upregulation of LncRNA ATB was discovered in NSCLC tissue samples and cell lines. LncRNA ATB was positively related to advanced tumor phase as well as lymph node metastasis. Cell function assays reflected LncRNA ATB expedited NSCLC cells proliferation, migration and invasion. LncRNA ATB promoted fibronectin 1 (FN1) expression via inhibiting miR-200b. Furthermore, LncRNA ATB depletion suppressed NSCLC cells proliferation, migration and invasion, while miR-200b inhibitor or pcDNA-FN1 rescued these effects. CONCLUSION: In summary, our outcomes elucidated that LncRNA ATB/miR-200b axis expedited NSCLC cells proliferation, migration and invasion by up-regulating FN1.

Clinical characteristics and cancer-specific survival analysis of double primary cancer patients with lung cancer as the first primary cancer.

The objective of this study is to explore the prognostic factors of double primary cancer patients with lung cancer as the first primary cancer (FPC). The Surveillance, Epidemiology, and End Results (SEER) database is a database established by the National Institutes of Research for cancer registration purposes, which collects relatively complete demographic characteristics and clinical data for assessing the epidemiological characteristics of cancer worldwide. Clinical data on patients with a clear histopathological diagnosis of double primary with lung cancer as the FPC were identified and collected from the SEER database from 2010 to 2015. Survival curves were plotted by Kaplan-Meier survival analysis. Independent prognostic factors of patients were analyzed by COX proportional risk model. Clinical data were collected from a total of 9306 patients, including 6516 patients in the modeling group and 2790 patients in the validation group. When we retrieved that the FPC was lung cancer, we found that the most common site of the second primary cancer was located in the respiratory system (54.0%). In addition, the most common site of first primary lung cancer in patients with double primary cancer was the right upper lobe (33.3%). A total of 14 independent prognostic factors were included, and the constructed survival nomogram had high accuracy and clinical applicability. The nomogram established in this study can help to raise awareness of clinical workers and the importance of such diseases, and guide the treatment and follow-up strategies.

Texture Analysis Based on Gd-EOB-DTPA-Enhanced MRI for Identifying Vessels Encapsulating Tumor Clusters (VETC)-Positive Hepatocellular Carcinoma.

PURPOSE: To determine the potential findings associated with vessels encapsulating tumor clusters (VETC)-positive hepatocellular carcinoma (HCC), with particular emphasis on texture analysis based on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI. METHODS: Eighty-one patients with VETC-negative HCC and 52 patients with VETC-positive HCC who underwent Gd-EOB-DTPA-enhanced MRI before curative partial hepatectomy were retrospectively evaluated in our institution. MRI texture analysis was performed on arterial phase (AP) and hepatobiliary phase (HBP) images. The least absolute shrinkage and selection operator (LASSO) logistic regression was used to select texture features most useful for identifying VETC-positive HCC. Univariate and multivariate analyses were used to determine significant variables for identifying the VETC-positive HCC in clinical factors and the texture features of MRI. Receiver operating characteristic (ROC) analysis and DeLong test were performed to compare the identified performances of significant variables for identifying VETC-positive HCC. RESULTS: LASSO logistic regression selected 3 features in AP and HBP images, respectively. In multivariate analysis, the Log-sigma-4.0-mm-3D first-order Kurtosis derived from AP images (odds ratio [OR] = 4.128, P = 0.001) and the Wavelet-LHL-GLDM Dependence Non Uniformity Normalized derived from HBP images (OR = 2.280, P = 0.004) were independent significant variables associated with VETC-positive HCC. The combination of the two texture features for identifying VETC-positive HCC achieved an AUC value of 0.844 (95% confidence interval CI, 0.777, 0.910) with a sensitivity of 80.8% (95% CI, 70.1%, 91.5%) and specificity of 74.1% (95% CI, 64.5%, 83.6%). CONCLUSION: Texture analysis based on Gd-EOB-DTPA-enhanced MRI can help identify VETC-positive HCC.

Serum IL-8 and VEGFA are Two Promising Diagnostic Biomarkers of Asthma-COPD Overlap Syndrome.

Background: Asthma-COPD overlap (ACO; previously referred to as asthma-COPD overlap syndrome) is characterized by persistent airflow limitation consistent with COPD, together with several distinguishing features of asthma. Asthma-COPD overlap syndrome is a condition of mixing symptoms of asthma and COPD, because of its complexity, it is difficult to find effective diagnostic markers in clinic. Purpose: Our aims were to detect the expression of serum cytokines in patients with asthma, explore the diagnostic potential of differential serum cytokines in ACOS. Patients and Methods: Ninety asthmatic patients were divided into ACOS group and non-ACOS group according to the major and minor criteria of ACOS, 15 kinds of cytokines including IL-3, IL-4, IL-8, IL-9, IL-13, IL-17A, VEGFA, VEGFC, VEGFD, bFGF, Fit-1 PIGF, Tie-2 were detected by MSD, and IL-27 and TGF-beta were determined by ELISA assay. Results: The serum levels of IL-9, VEGFA and PIGF in patients with ACOS were significantly higher than those in non-ACOS group (P<0.05, respectively), while the level of IL-8 and IL-17A in subjects with ACOS was lower than that in the non-ACOS group (P<0.05, respectively). We analyzed the correlation between several difference factors and FEV1/FVC% in the ACOS group, found VEGFA was negatively correlated with FEV1/FVC%, while IL-8 and IL-17A were positively correlated with FEV1/FVC%. Finally, three correlation factors were analyzed by ROC curve for the occurrence of ACOS. Conclusion: The results suggested that IL-8 was highly sensitive and VEGFA was highly specificity, both of which could be used as biomarkers for the diagnosis of ACOS.

Exosomal miR-106b serves as a novel marker for lung cancer and promotes cancer metastasis via targeting PTEN.

As novel non-invasive tumor diagnostic biomarkers, exosomal bioactive miRNAs have received increasing attention. Herein, the aim of this study is to explore the clinical values and roles of exosomal miR106b in lung cancer. The exosomal miR-106b level was much higher in the serum of patients with lung cancer than that in healthy volunteers. Also, the exosomal miR-106b level in the lung cancer patient serum was associated with TNM stages and lymph node metastasis. Furthermore, exosomal miR-106b enhanced the migrated and invasive ability of lung cancer cells and increased the MMP-2 and MMP-9 expression. Mechanistically, exosomal miR-106b could target PTEN, and promote lung cancer cell migration and invasion. More importantly, PTEN overexpression reversed the effect of exosomal miR-106b on lung cancer cell migration and invasion. Taken together, these findings indicate that exosomal miR-106b may be a promising diagnostic biomarker and drug target for patients with lung cancer.

[Schwannoma in the right upper mediastinum with hemorrhagic cystic degeneration: a case report and review of literature].

case of schwannoma with hemorrhagic cystic degeneration in the right upper mediastinum was admitted to the Affiliated Hospital of Ningbo University in July 2010. The patient shows symptoms of cough and shortness of breath. He received video-assisted thoracoscopic resection of right upper mediastinal mass. This disease displayed different symptoms depending on tumor size and location.

Functional polymorphisms in the promoter region of MMP-2 and MMP-9 and susceptibility to obstructive sleep apnea.

Genetic susceptibility to obstructive sleep apnea (OSA) has been a research focus in the scientific community in the past few years. In this study, we recruited 375 subjects to investigate whether functional polymorphisms in the promoter region of matrix metalloproteinase (MMP)-2 (-1306C/T) and MMP-9 (-1562C/T) increased susceptibility to OSA. Our study showed no significant association between MMP-2 -1306C/T polymorphism and risk of OSA (T vs. C: OR = 1.01, 95% CI = 0.67-1.52; P = 0.97). Compared with the MMP-9 -1562C allele, the -1562T allele was associated with increased risk of OSA (T vs. C: OR = 1.56, 95% CI = 1.02-2.39; P = 0.04). However, neither MMP-2 -1306C/T nor MMP-9 -1562C/T polymorphism was found to be associated with severity of the disease. Our study suggested that the MMP-2 -1306C/T polymorphism was not associated with OSA susceptibility, whereas the MMP-9 -1562T allele was associated with increased risk of OSA.

Macrolide therapy in cryptogenic organizing pneumonia: A case report and literature review.

Cryptogenic organizing pneumonia (COP) is a pulmonary disorder associated with nonspecific clinical presentations. The macrolide class of antimicrobial agents is widely used to treat infectious and inflammatory respiratory diseases in humans. The present study reports a case of COP that was effectively treated with azithromycin in combination with glucocorticoid. A literature review of similar cases is also presented. It was found that all COP patients in the literature received macrolide treatment, including six cases with unknown clinical outcomes. For the remaining 29 patients, 20 patients initially received the macrolide as a single therapy and 4/5 of them (16 cases) were cured with a treatment time of 3-14 months, while 1/5 (4 cases) showed no improvement after treatment for 1 month and were switched to a glucocorticoid or combination treatment with a glucocorticoid, after which the disease was finally well-controlled. Side-effects of macrolide were rare. Based on this analysis, it is recommended that macrolides can be used as a first-line therapy in patients with mild COP. For patients with recurrent COP, it is suggested that macrolides should be used as an adjunctive therapy with other treatments, such as a glucocorticoid.

Vascular endothelial growth factor genotypes and haplotypes contribute to the susceptibility of obstructive sleep apnea syndrome.

BACKGROUND: To investigate whether VEGF polymorphisms (-460 T/C, +405 G/C, and +936 C/T)/haplotypes influence the susceptibility of obstructive sleep apnea (OSA). METHOD: A prospective case-control study was conducted to evaluate the genetic effects of VEGF polymorphisms on the development of OSA. 150 patients and 225 healthy controls were recruited for this study and their genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The odds ratios (OR) and 95% confidence intervals (CI) were calculated by logistic regression analysis. RESULT: Our study showed that the -460 C allele (C vs. T: OR = 1.95, 95% CI = 1.38-2.76) and +936 T allele (T vs. C: OR = 1.48, 95% CI = 1.02-2.15) were associated with an increased OSA risk, whereas +405 C allele was associated with a decreased susceptibility to OSA (C vs. G: OR = 0.61, 95% CI = 0.45-0.83). Compared with the most common haplotype CCT, CGC (OR = 2.22, 95% CI = 1.19-4.13) and TGC (OR = 3.83, 95% CI = 1.56-9.40) were associated with a significantly increased risk of OSA. CONCLUSION: These observations implied that VEGF gene polymorphisms might be associated with the susceptibility to OSA. These results need to be validated by other independent studies, especially in diverse ethnic populations.

TGF-ß1, IL-6, and TNF-α in bronchoalveolar lavage fluid: useful markers for lung cancer?

Changes of cytokines in bronchoalveolar lavage fluid (BALF) reflect immunologic reactions of the lung in pulmonary malignancies. Detection of biomarkers in BALF might serve as an important method for differential diagnosis of lung cancer. A total of 78 patients admitted into hospital with suspected lung cancer were included in our study. BALF samples were obtained from all patients, and were analyzed for TGF-ß1, IL-6, and TNF-α using commercially available sandwich ELISA kits. The levels of TGF-ß1 in BALF were significantly higher in patients with lung cancer compared with patients with benign diseases (P = 0.003). However, no significant difference of IL-6 (P = 0.61) or TNF-α (P = 0.72) in BALF was observed between malignant and nonmalignant groups. With a cut-off value of 10.85 pg/ml, TGF-ß1 showed a sensitivity of 62.2%, and a specificity of 60.6%, in predicting the malignant nature of pulmonary disease. Our data suggest that TGF-ß1 in BALF might be a valuable biomarker for lung cancer. However, measurement of IL-6 or TNF-α in BALF has poor diagnostic value in lung cancer.

[Combination of narrow band imaging (NBI) and autofluorescence bronchoscopy (AFB) in the assessment of central lung cancer].

OBJECTIVE: To assess the diagnostic value of narrow-band imaging(NBI) in the diagnosis of central lung cancer. METHODS: Patients (n = 153) suspected of having lung cancer underwent white light bronchoscopy(WLB), NBI and autofluorescence bronchoscopy(AFB) in turn. At least 3 biopsies in each case were taken from sites visualized as lesions. The sensitivity and specificity of NBI, AFB and combination of NBI and AFB were compared. RESULTS: There were 106 male (69.3%) and 47 female patients (30.7%). By NBI, 91 and 62 cases were positive and negative respectively. The sensitivity and specificity of NBI were 63.5% (87/137) and 75.0% (12/16) respectively. By AFB, 140 and 13 cases were positive and negative respectively. The sensitivity and specificity of AFB were 94.2% (129/137) and 87.5% (5/16) respectively. By NBI combined with AFB, 133 and 20 cases were positive and negative respectively, the sensitivity and specificity being 95.6% (131/137) and 87.5% (14/16) respectively. The difference of specificity between NBI plus AFB and AFB alone was significant (P < 0.01), but the difference of sensitivity between NBI plus AFB and AFB alone(P > 0.05) was not. The difference of specificity between NBI plus AFB and NBI alone was significant (P < 0.01), but the P value of specificity between NBI plus AFB and NBI was 0.03. CONCLUSION: Combination of NBI and AFB could increase the specificity of lung cancer diagnosis compared to AFB alone.

C-reactive protein as a prognostic marker in chronic obstructive pulmonary disease.

The present study aimed to evaluate whether circulating C-reactive protein (CRP) levels are a biomarker of systemic inflammation and a significant predictor of future chronic obstructive pulmonary disease (COPD) outcome. During the study, 116 patients with stable COPD and 35 age- and gender-matched healthy subjects with normal pulmonary function were observed. Patient follow-up was also performed to evaluate the strength of the associations between CRP levels and future outcomes. The observations from the present study showed that serum CRP levels were significantly higher in stable COPD patients than in control subjects (4.48±0.83 vs. 1.01±0.27 mg/l, respectively; P<0.05). In addition, it was identified that a serum CRP concentration of >3 mg/l is a poor prognostic variable of COPD compared with a CRP concentration of ≤3 mg/l [hazard ratio (HR), 2.71; 95% confidence interval (CI), 1.05-6.99; P<0.05]. A quantitative synthesis of four studies including 1,750 COPD patients was performed and statistically similar results were obtained (HR, 1.54; 95% CI, 1.14-2.07; P<0.01). The present study showed that circulating CRP levels are higher in stable COPD patients and, therefore, may be used as a long-term predictor of future outcomes. These observations highlight the importance of high sensitivity CRP assays in patients with stable COPD.

Evaluation of VEGF-C and tumor markers in bronchoalveolar lavage fluid for lung cancer diagnosis.

A total of 87 patients were enrolled and bronchoalveolar lavage fluid (BALF) samples were obtained from all subjects. A significant difference was found in BALF VEGF-C level between patients with squamous cell carcinoma and benign diseases (P = 0.043). In addition, the concentration of NSE in BALF form the malignant group was significantly higher compared with that of the benign groups (P = 0.018). However, no statistical difference was observed in BALF CEA (P = 0.375) or CYFRA21-1 (P = 0.838) between lung cancer patients and nonmalignant controls. With a cut-off value of 2.06 ng/ml, NSE had a sensitivity of 72.9%, a specificity of 69.2%, respectively, in predicting the malignant nature of pulmonary mass. Our study observed that the level of VEGF-C was increased in BALF of patients with squamous cell carcinoma. Moreover, we found that NSE was significantly higher in BALF of lung cancer patients than in benign diseases.

Utility of VEGF and sVEGFR-1 in bronchoalveolar lavage fluid for differential diagnosis of primary lung cancer.

Published data have shown that the levels of vascular endothelial growth factor (VEGF) and soluble VEGF receptor-1 (sVEGFR-1) in plasma and pleural effusion might be usefulness for lung cancer diagnosis. Here, we performed a prospective study to investigate the utility of VEGF and sVEGFR-1 in bronchoalveolar lavage fluid (BALF) for differential diagnosis of primary lung cancer. A total of 56 patients with solitary pulmonary massed by chest radiograph or CT screening were enrolled in this study. BALF and plasma samples were obtained from all patients and analyzed for VEGF and sVEGFR-1 using a commercially available sandwich ELISA kit. The results showed that the levels of VEGF in BALF were significantly higher in patients with a malignant pulmonary mass compared with patients with a benign mass (P < 0.001). However, no significant difference of sVEGFR-1 in BALF was found between malignant and non-malignant groups (P = 0.43). With a cut-off value of 214 pg/ml, VEGF showed a sensitivity and specificity of 81.8% and 84.2%, respectively, in predicting the malignant nature of a solitary pulmonary mass. Our study suggests that VEGF is significantly increased in BALF among patients with lung cancer than in benign diseases. Measurement of VEGF in BALF might be helpful for differential diagnosis of primary lung cancer.

[Combination of narrow-band imaging and autofluorescence imaging videobronchoscopy in the assessment of lung cancer].

BACKGROUND: Narrow-band imaging (NBI) and autofluorescence imaging (AFI) are new bronchoscopy technologies that are important in lung cancer diagnosis. The aim of this study is to determine whether or not the combination of these two technologies can improve sensitivity and specificity of lung cancer diagnosis. METHODS: A total of 137 patients who manifested symptoms of lung cancer were investigated in this project. All of the examinations were performed based on an Olympus Evis Lucera bronchoscopy system. The patients were examined by white light bronchoscopy (WLB), NBI and AFI. At least three biopsies from body parts visualized as lesions were obtained from each patient. RESULTS: WLB sensitivity and specificity were 56.6% and 62.5%, respectively. NBI sensitivity and specificity were 71.3% and 75.0%, respectively. AFI sensitivity and specificity were 82.2% and 25.0%, respectively. The sensitivity and the specificity of the combined NBI and AFI were 94.6% and 87.5%, respectively. The sensitivity and the specificity of the combined NBI and AFI were significantly higher than those of AFI alone (P<0.01). Likewise, the sensitivity and the specificity of the combined NBI and AFI were significantly higher than those of NBI alone (P<0.05). CONCLUSIONS: NBI or AFI exhibited higher sensitivity of lung cancer diagnosis than WLB. Combined NBI and AFI also showed significantly higher sensitivity and specificity than NBI or AFI.

Short-cut nitrification in biological aerated filters with modified zeolite and nitrifying sludge.

Autotrophic domestication for short-cut nitrification (SCN) and microorganism immobilization was carried out in a lab-scale biological aerated filters (BAFs) system with activated sludge. Zeolite was chosen as fillings and modified to enlarge the specific surface and to remove toxic metal ions. After thirty-day domestication and immobilization, the NH4(+)-N removal capacity increased to 76.51 mg/g dry sludge (DS) and the ratio of NO2(-)-N converted from NH4(+)-N reached to 91.2% finally. The analysis of growth kinetics indicated that free ammonia should be the key factor for SCN. The abundance variation of nitrifiers, measured by qPCR, showed that AOB was enriched successfully and NOB was washed out. The results also showed that modified zeolite should be more beneficial to the specific immobilization of AOB than natural zeolite. The shift in the community structure of AOB during the domestication by DGGE profile was investigated.

Polymorphism of VEGF-460C/T associated with the risk and clinical characteristics of lung cancer in Chinese population.

Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis in the process of tumor growth and metastasis. Different VEGF gene polymorphisms have been shown to result in different VEGF protein expression in cancer cells and tumor angiogenic activity. We conducted a case-control study to evaluate the genetic effects of VEGF-460C/T polymorphism on the development of lung cancer. One hundred and twenty-six lung cancer patients and 160 sex-, age-, and ethnic-matched healthy controls were recruited for this study. The genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Odds ratios (ORs) and 95 % confidence intervals (CI) were calculated by logistic regression analysis. Our study showed that the TT genotype was associated with increased lung cancer risk than those with the CC (OR = 1.99, 95 % CI 1.05-3.77) or CT/CC (OR = 1.89, 95 % CI 1.17-3.06) genotype. Moreover, it was observed that the TT genotype associated with the advanced stage among lung cancer patients (TT vs. CC: OR = 3.09, 95 % CI 1.10-8.66). More studies are needed to detect VEGF-460C/T polymorphism and its association with lung cancer in different ethnic populations incorporated with environmental exposures.

The abundance and diversity of ammonia-oxidizing bacteria in activated sludge under autotrophic domestication.

Ammonia-oxidizing bacteria (AOB) play a key role in nitrogen-removal wastewater treatment plants (WWTPs) as they can transform ammonia into nitrite. AOB can be enriched in activated sludge through autotrophic domestication although they are difficult to be isolated. In this study, autotrophic domestication was carried out in a lab-scale sequencing-batch-reactor (SBR) system with two activated sludge samples. The ammonia removal capacity of the sludge samples increased during the domestication, and pH exhibited a negative correlation with the ammonia removal amount, which indicated that it was one important factor of microbial ammonia oxidation. The count of AOB, measured by the most probable number (MPN) method, increased significantly during autotrophic domestication as ammonia oxidation efficiency was enhanced. We investigated the changes in the community structure of AOB before and after domestication by amoA clone library and T-RFLP profile. It showed that AOB had been successfully enriched and the community structure significantly shifted during the domestication. Two groups of AOB were found in sludge samples: Nitrosomonas-like group remained predominant all the time and Nitrosospira-like group changed obviously. Simultaneously, the total heterotrophic bacteria were investigated by MPN and Biolog assay. The metabolic diversity of heterotrophs had changed minutely, although the count of them decreased significantly and lost superiority of microbial communities in the sludge.

Association between angiotensin-converting enzyme I/D polymorphism and asthma risk: a meta-analysis involving 11,897 subjects.

BACKGROUND: Genetic susceptibility to asthma has been a research focus in the scientific community. Several studies have been conducted in recent years to evaluate the risk of asthma and insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE). However, the results remain conflicting rather than conclusive. METHODS: We carried out a search in Medline, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) database for relevant studies. Data were extracted using a standardized form and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the association. RESULTS: Our meta-analysis on 11,897 subjects from all available studies showed that the DD genotype was associated with increased asthma risk than those with the II (OR = 1.59, 95% CI = 1.20-2.12) or ID/II (OR = 1.62, 95% CI = 1.24-2.10) genotype. Stratified analyses by ethnicity (Europeans and Asians) and age (adults and children) obtained statistically similar results in the two genetic models. In the subgroup analysis by source of controls, the DD genotype was associated with a significantly elevated risk of asthma among population-based controls (DD vs. II: OR = 2.27, 95% CI = 1.45-3.56) but not hospital-based controls (DD vs. II: OR = 1.18, 95% CI = 0.93-1.49). CONCLUSIONS: This meta-analysis provides strong evidence that the I/D polymorphism of ACE is associated with asthma risk. Additional well-designed large studies were required for the validation of our results, especially in African populations.