Comparison of the clinicoradiological features and outcomes of lymphoepithelioma-like cholangiocarcinoma and conventional intrahepatic cholangiocarcinoma: A propensity score matching analysis.

BACKGROUND/PURPOSE: Lymphoepithelioma-like cholangiocarcinoma (LELCC) is a rare variant of intrahepatic cholangiocarcinoma (ICC). We aim to analyze the differences in the clinical and radiological features of LELCC and ICC. METHODS: Between January 2003 and December 2019, a total of 21 patients diagnosed with LELCC were retrospectively enrolled, and 84 patients with ICC were selected through propensity score matching by sex, age, and initial cancer stage. The clinical characteristics, pathological findings, and radiological features were analyzed. The differences in overall survival (OS) between LELCC and ICC were evaluated using the Kaplan-Meier method. RESULTS: The serum carbohydrate antigen 19-9 (CA 19-9) level was higher in the ICC group than in the LELCC group (77.9 vs 30.0 U/mL, p = 0.004). Non-rim arterial phase hyperenhancement (47.1% vs 13.7%, p = 0.005) and portovenous washout (35.3% vs 4.1%, p = 0.001) were more frequently observed in the LELCC group than in the ICC group. Intrahepatic duct dilatation was a distinct feature of the ICC group. The 5-year OS rates in the LELCC and ICC groups were 69.3% and 58.2%, respectively (p = 0.047). The 5-year OS of patients with stages I and II LELCC between ICC were not significantly different (90.0% vs 83.4%, p = 0.464). However, the 5-year OS of patients with stages III and IV LELCC was more favorable than that of patients with ICC (29.2% vs 23.0%, p = 0.017). CONCLUSIONS: LELCC had a favorable outcome and several different clinicoradiological features compared with ICC.

Validation of the Machine Learning-Based Stroke Impact Scale With a Cross-Cultural Sample.

IMPORTANCE: The machine learning-based Stroke Impact Scale (ML-SIS) is an efficient short-form measure that uses 28 items to provide domain scores comparable to those of the original 59-item Stroke Impact Scale-Third Edition (SIS 3.0). However, its utility is largely unknown because it has not been cross-validated with an independent sample. OBJECTIVE: To examine the ML-SIS's comparability and test-retest reliability with that of the original SIS 3.0 in an independent sample of people with stroke. DESIGN: Comparability was examined with the coefficient of determination (R2), mean absolute error, and root-mean-square error (RMSE). Test-retest reliability was examined using the intraclass correlation coefficient (ICC). SETTING: Five hospitals in Taiwan. PARTICIPANTS: Data of 263 persons with stroke were extracted from a previous study; 144 completed repeated assessments after a 2-wk interval. RESULTS: High R2 (.87-.95) and low mean absolute error or RMSE (about 2.4 and 3.3) of the domain scores, except for the Emotion scores (R2 = .08), supported the comparability of the two measures. Similar ICC values (.39-.87 vs. .46-.87) were found between the two measures, suggesting that the ML-SIS is as reliable as the SIS 3.0. CONCLUSIONS AND RELEVANCE: The ML-SIS provides scores mostly identical to those of the original measure, with similar test-retest reliability, except for the Emotion domain. Thus, it is a promising alternative that can be used to lessen the burden of routine assessments and provide scores comparable to those of the original SIS 3.0. Plain-Language Summary: The machine learning-based Stroke Impact Scale (ML-SIS) is as reliable as the original Stroke Impact Scale-Third Edition, except for the Emotion domain. Thus, the ML-SIS can be used to improve the efficiency of clinical assessments and also relieve the burden on people with stroke who are completing the assessments.

Pancreatic Cancer Detection on CT Scans with Deep Learning: A Nationwide Population-based Study.

Background Approximately 40% of pancreatic tumors smaller than 2 cm are missed at abdominal CT. Purpose To develop and to validate a deep learning (DL)-based tool able to detect pancreatic cancer at CT. Materials and Methods Retrospectively collected contrast-enhanced CT studies in patients diagnosed with pancreatic cancer between January 2006 and July 2018 were compared with CT studies of individuals with a normal pancreas (control group) obtained between January 2004 and December 2019. An end-to-end tool comprising a segmentation convolutional neural network (CNN) and a classifier ensembling five CNNs was developed and validated in the internal test set and a nationwide real-world validation set. The sensitivities of the computer-aided detection (CAD) tool and radiologist interpretation were compared using the McNemar test. Results A total of 546 patients with pancreatic cancer (mean age, 65 years ± 12 [SD], 297 men) and 733 control subjects were randomly divided into training, validation, and test sets. In the internal test set, the DL tool achieved 89.9% (98 of 109; 95% CI: 82.7, 94.9) sensitivity and 95.9% (141 of 147; 95% CI: 91.3, 98.5) specificity (area under the receiver operating characteristic curve [AUC], 0.96; 95% CI: 0.94, 0.99), without a significant difference (P = .11) in sensitivity compared with the original radiologist report (96.1% [98 of 102]; 95% CI: 90.3, 98.9). In a test set of 1473 real-world CT studies (669 malignant, 804 control) from institutions throughout Taiwan, the DL tool distinguished between CT malignant and control studies with 89.7% (600 of 669; 95% CI: 87.1, 91.9) sensitivity and 92.8% specificity (746 of 804; 95% CI: 90.8, 94.5) (AUC, 0.95; 95% CI: 0.94, 0.96), with 74.7% (68 of 91; 95% CI: 64.5, 83.3) sensitivity for malignancies smaller than 2 cm. Conclusion The deep learning-based tool enabled accurate detection of pancreatic cancer on CT scans, with reasonable sensitivity for tumors smaller than 2 cm. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Aisen and Rodrigues in this issue.

Detection of pancreatic cancer with two- and three-dimensional radiomic analysis in a nationwide population-based real-world dataset.

BACKGROUND: CT is the major detection tool for pancreatic cancer (PC). However, approximately 40% of PCs < 2 cm are missed on CT, underscoring a pressing need for tools to supplement radiologist interpretation. METHODS: Contrast-enhanced CT studies of 546 patients with pancreatic adenocarcinoma diagnosed by histology/cytology between January 2005 and December 2019 and 733 CT studies of controls with normal pancreas obtained between the same period in a tertiary referral center were retrospectively collected for developing an automatic end-to-end computer-aided detection (CAD) tool for PC using two-dimensional (2D) and three-dimensional (3D) radiomic analysis with machine learning. The CAD tool was tested in a nationwide dataset comprising 1,477 CT studies (671 PCs, 806 controls) obtained from institutions throughout Taiwan. RESULTS: The CAD tool achieved 0.918 (95% CI, 0.895-0.938) sensitivity and 0.822 (95% CI, 0.794-0.848) specificity in differentiating between studies with and without PC (area under curve 0.947, 95% CI, 0.936-0.958), with 0.707 (95% CI, 0.602-0.797) sensitivity for tumors < 2 cm. The positive and negative likelihood ratios of PC were 5.17 (95% CI, 4.45-6.01) and 0.10 (95% CI, 0.08-0.13), respectively. Where high specificity is needed, using 2D and 3D analyses in series yielded 0.952 (95% CI, 0.934-0.965) specificity with a sensitivity of 0.742 (95% CI, 0.707-0.775), whereas using 2D and 3D analyses in parallel to maximize sensitivity yielded 0.915 (95% CI, 0.891-0.935) sensitivity at a specificity of 0.791 (95% CI, 0.762-0.819). CONCLUSIONS: The high accuracy and robustness of the CAD tool supported its potential for enhancing the detection of PC.

Discrimination of invasive lung adenocarcinoma from Lung-RADS category 2 nonsolid nodules through visual assessment: a retrospective study.

OBJECTIVES: Invasive adenocarcinomas (IADs) have been identified among nonsolid nodules (NSNs) assigned as Lung Imaging Reporting and Data System (Lung-RADS) category 2. This study used visual assessment for differentiating IADs from noninvasive lesions (NILs) in this category. METHODS: This retrospective study included 222 patients with 242 NSNs, which were resected after preoperative computed tomography (CT)-guided dye localization. Visual assessment was performed by using the lung and bone window (BW) settings to classify NSNs into BW-visible (BWV) and BW-invisible (BWI) NSNs. In addition, nodule size, shape, border, CT attenuation, and location were evaluated and correlated with histopathological results. Logistic regression was performed for multivariate analysis. A p value of < 0.05 was considered statistically significant. RESULTS: A total of 242 NSNs (mean diameter, 7.6 ± 2.8 mm), including 166 (68.6%) BWV and 76 (31.4%) BWI NSNs, were included. IADs accounted for 31% (75) of the nodules. Only 4 (5.3%) IADs were identified in the BWI group and belonged to the lepidic-predominant (n = 3) and acinar-predominant (n = 1) subtypes. In univariate analysis for differentiating IADs from NILs, the nodule size, shape, CT attenuation, and visual classification exhibited statistical significance. Nodule size and visual classification were the significant predictors for IAD in multivariate analysis with logistic regression (p < 0.05). The sensitivity, specificity, positive predictive value, and negative predictive value of visual classification in IAD prediction were 94.7%, 43.1%, 42.8%, and 94.7%, respectively. CONCLUSIONS: The window-based visual classification of NSNs is a simple and objective method to discriminate IADs from NILs. CLINICAL RELEVANCE STATEMENT: The present study shows that using the bone window to classify nonsolid nodules helps discriminate invasive adenocarcinoma from noninvasive lesions. KEY POINTS: • Evidence has shown the presence of lung adenocarcinoma in Lung-RADS category 2 nonsolid nodules. • Nonsolid nodules are classified into the bone window-visible and the bone window-invisible nonsolid nodules, and this classification differentiates invasive adenocarcinoma from noninvasive lesions. • The Lung-RADS category 2 nonsolid nodules are unlikely invasive adenocarcinoma if they show nonvisualization in the bone window.

Test-Retest Reliability and Responsiveness of the Computerized Adaptive Testing System of the Functional Assessment of Stroke.

OBJECTIVE: To examine the test-retest reliability, responsiveness, and clinical utility of the Computerized Adaptive Testing System of the Functional Assessment of Stroke (CAT-FAS) in persons with stroke. DESIGN: Repeated measurements design. SETTING: A department of rehabilitation in a medical center. PARTICIPANTS: 30 persons with chronic stroke (for test-retest reliability) and 65 persons with subacute stroke (for responsiveness) were recruited. To examine the test-retest reliability, the participants received measurements twice at 1-month intervals. To examine the responsiveness, the data were collected at admission and discharge from hospital. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASUREMENT TOOL: CAT-FAS. RESULTS: The intra-class correlation coefficients of the CAT-FAS were ≥0.82, indicating good to excellent test-retest reliability. The Kazis' effect size and standardized response mean of the CAT-FAS were ≥0.96, indicating good group-level responsiveness. For individual-level responsiveness, approximately two-thirds of the participants exceeded the conditional minimal detectable change. On average, the CAT-FAS was completed within 9 items and 3 minutes per administration. CONCLUSIONS: Our results suggest the CAT-FAS is an efficient measurement tool with good to excellent test-retest reliability and responsiveness. In addition, the CAT-FAS can be used routinely in clinical settings to monitor progress of the crucial 4 domains for persons with stroke.

Test-Retest Reliability and Responsiveness of the Computerized Adaptive Test of Social Functioning in Persons With Stroke.

OBJECTIVE: To examine the test-retest reliability, minimal detectable change (MDC), responsiveness, and efficiency of the Computerized Adaptive Test of Social Functioning (Social-CAT) in patients with stroke. DESIGN: Repeated-assessments design. SETTING: A department of rehabilitation of a medical center. PARTICIPANTS: In total, 31 patients with chronic stroke and 65 patients with subacute stroke were recruited. INTERVENTION: Not available. MAIN OUTCOME MEASURE: Social-CAT. RESULTS: The Social-CAT showed acceptable test-retest reliability (intraclass correlation coefficient, 0.80) and small random measurement error (MDC%: 18.0%). However, heteroscedasticity was found (r between the means and the absolute change scores: 0.32), so the MDC% adjusted cut-off score is recommended for determining real improvement. Regarding responsiveness, the Social-CAT showed large differences (Kazis' effect size and standardized mean response: 1.15 and 1.09, respectively) in subacute patients. Regarding efficiency, the Social-CAT required an average of 5 items and less than 2 minutes for completion. CONCLUSIONS: Our findings indicate that the Social-CAT is a reliable and efficient measure with good test-retest reliability, small random measurement error, and good responsiveness. Thus, the Social-CAT is a useful outcome measure for routine monitoring of the changes in social function of patients with stroke.

Applications of artificial intelligence in pancreatic and biliary diseases.

The application of artificial intelligence (AI) in medicine has increased rapidly with respect to tasks including disease detection/diagnosis, risk stratification, and prognosis prediction. With recent advances in computing power and algorithms, AI has shown promise in taking advantage of vast electronic health data and imaging studies to supplement clinicians. Machine learning and deep learning are the most widely used AI methodologies for medical research and have been applied in pancreatobiliary diseases for which diagnosis and treatment selection are often complicated and require joint consideration of data from multiple sources. The aim of this review is to provide a concise introduction of the major AI methodologies and the current landscape of AI research in pancreatobiliary diseases.

Fluoroscopic-guided nasogastric tube placement in patients with advanced head and neck cancers.

BACKGROUND/PURPOSE: Enteral feeding, mainly by using a nasogastric tube (NGT), is generally favored over parenteral supplementation in head and neck cancer (HNC) patients with dysphagia. However, the placement of a NGT, either blindly or by endoscopy, is technically challenging in these patients due to the obstructive mass and the altered regional anatomy. The aim of this retrospective study was to estimate the clinical feasibility and safety of fluoroscopic-guided NGT placement in patients with advanced HNC. METHODS: Between January 2010 and June 2018, a total of 572 fluoroscopic-guided NGT placements were performed on 231 patients. Technical success was defined as successful insertion of the NGT into the stomach with proper positioning, which was verified by air injection into the NGT. Complications, including aspiration pneumonia, and the ones requiring intensive care, or procedure-related death, were recorded. RESULTS: Technical success was obtained in 558 (97.6%) procedures, and the other 14 (2.4%) procedures failed because of patient intolerance (n = 1) and high-grade obstruction (n = 13). Of the high-grade obstruction patients, eight (61.5%) were shifted to percutaneous radiological gastrostomy, two (15.4%) to surgical feeding jejunostomy, one (7.6%) to endoscopic balloon dilatation, and two (15.4%) to orogastric tube insertion. The average procedure time and fluoroscopy time were 11.7 ± 7.4 min and 3.1 ± 3.1 min, respectively. There were no major complications. CONCLUSION: Our results show that fluoroscopic-guided NGT placement is a highly safe and effective procedure for patients with advanced HNC requiring enteral feeding.

Computed tomography predict regression of coronary artery aneurysm in patients with Kawasaki disease.

BACKGROUND/PURPOSE: The study evaluated possible factors influencing the regression of coronary artery aneurysm (CAA) in patients with Kawasaki disease (KD) through electrocardiographically gated cardiac computed tomography (CT). METHODS: 18 patients with KD exhibited CAAs in at least 2 CT examinations conducted from December 2004 to September 2015, and 37 aneurysms were observed. Every aneurysm was corrected through the descending aorta at the origin level of the left main coronary artery under a normal distribution and measured under a fixed window level. These aneurysms were divided into 2 groups according to regression. Clinical symptoms, laboratory data, and imaging characteristics of both groups were analyzed. RESULTS: All the aneurysms of 4 patients decreased in size, and totally, 14 aneurysms (37%) regressed. CAA regression tends to occur early after disease onset. No significant differences were observed in sex, aneurysm location, and the distance to the orifice between the 2 groups. The aneurysms with no calcification (p = 0.012), smaller diameter (p = 0.004), younger disease onset age (p = 0.048), and ectatic shape (p < 0.001) were more likely to regress according to univariate analysis. Receiver operating characteristic analysis revealed that the possible cut-off point of the maximal diameter to yield the highest sensitivity (91.3%) and specificity (92.9%) to predict CAA regression was 5.6 mm. CONCLUSION: Calcified CAAs in patients with KD was less likely to regress. The aneurysm size and shape as well as disease onset age were possible factors influencing regression.

Reduced threshold of optically pumped amplified spontaneous emission and narrow line-width electroluminescence at cutoff wavelength from bilayer organic waveguide devices.

We present a detailed study of the optically and electrically pumped emission in the BSB-Cz/PVK bilayer waveguide devices. By optical pumping we demonstrate that PVK as a spacer between fluorescent BSB-Cz and ITO electrode allows the significant reduction of the threshold for amplified spontaneous emission (ASE) of BSB-Cz. The simulation provides a better understanding of how the PVK thickness affects the waveguide mode field distribution and hence the ASE threshold of BSB-Cz. On the other hand, the BSB-Cz/PVK bilayer OLED exhibits the external quantum efficiency of >1% and anisotropic electroluminescence with spectrally narrowed edge emission at the cutoff wavelength controlled by the BSB-Cz thickness. When tuning the cutoff wavelength to match the peak gain of BSB-Cz, we demonstrate an intense, particularly narrow edge emission (~5 nm) without obvious degradation of efficiency at a high current density of 1000 mA/cm2, suggesting a reliable device performance for high-power applications and further exploration of electrically-pumped ASE.

Development of the Low-Temperature Inducible System for Recombinant Protein Production in Escherichia coli Nissle 1917.

The pET system is commonly used for producing foreign proteins in Escherichia coli, but its reliance on the costly and metabolically demanding inducer IPTG limits its industrial use. This study engineered a low-temperature inducible system (LTIS) in E. coli Nissle 1917 (EcN) by combining the T7 expression system with the thermal inducible mechanism CI857-λPRPL to generate the new LTIS strain, ENL7P. The strain ENL7P-sfGFP-Km underwent overnight culture at 37 °C for 14-16 h, followed by subculturing at 30 °C for 24 h. This resulted in a notable 5.53-fold increase in the sfGFP induction rate when the strain was cultivated under 37-30 °C conditions. Moreover, gene expression was induced using a two-stage strategy. Initially, the strain was cultured overnight at 39 °C for 14-16 h, followed by a subculture at 30 °C for 6 h, and finally, another subculture at 30 °C for 24 h. This cultivation strategy led to an impressive 158.37-fold induction rate for sfGFP. Similar effects could be achieved through utilization of the LTIS system for inducing the production of thermophilic trehalose synthase from Thermus antranikianii (TaTS). The results of this study proved that the LTIS system has the potential for industrial applications.

Xin-Yi-Qing-Fei-Tang and its critical components reduce asthma symptoms by suppressing GM-CSF and COX-2 expression in RBL-2H3 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine (TCM) XYQFT is composed of 10 herbs. According to the NHIRD, XYQFT is one of the top ten most commonly used TCM prescriptions for asthma treatment. AIM OF THE STUDY: The aim of this study was to explore whether XYQFT reduces asthma symptoms in a mouse model of chronic asthma and determine the immunomodulatory mechanism of mast cells. MATERIALS AND METHODS: BALB/c mice were intratracheally (it) stimulated with 40 µL (2.5 µg/µL) of Dermatophagoides pteronyssinus (Der p) once a week for 6 consecutive weeks and orally administered XYQFT at 1 g/kg 30 min before Der p stimulation. Airway hypersensitivity, inflammatory cells in the BALF and total IgE in the blood were assessed in mice. In addition, RBL-2H3 cells (mast cells) were stimulated with DNP-IgE, after which different concentrations of XYQFT were added for 30 min to evaluate the effect of XYQFT on the gene expression and degranulation of DNP-stimulated RBL-2H3 cells. After the compounds in XYQFT were identified using LC‒MS/MS, the PBD method was used to identify the chemical components that inhibited the expression of the GM-CSF and COX-2 genes in mast cells. RESULTS: The airway hypersensitivity assay demonstrated that XYQFT significantly alleviated Der p-induced airway hypersensitivity. Moreover, cell counting and typing of bronchoalveolar lavage fluid revealed a significant reduction in Der p-induced inflammatory cell infiltration with XYQFT treatment. ELISA examination further indicated a significant decrease in Der p-induced total IgE levels in serum following XYQFT administration. In addition, XYQFT inhibited the degranulation and expression of genes (IL-3, IL-4, ALOX-5, IL-13, GM-CSF, COX-2, TNF-α, and MCP-1) in RBL-2H3 cells after DNP stimulation. The compounds timosaponin AIII and genkwanin in XYQFT were found to be key factors in the inhibition of COX-2 and GM-CSF gene expression in mast cells. CONCLUSION: By regulating mast cells, XYQFT inhibited inflammatory cell infiltration, airway hypersensitivity and specific immunity in a mouse model of asthma. In addition, XYQFT synergistically inhibited the expression of the GM-CSF and COX-2 genes in mast cells through timosaponin AIII and genkwanin.

New continuous fluorometric assay for bacterial transglycosylase using Förster resonance energy transfer.

The emergence of antibiotic resistance has prompted scientists to search for new antibiotics. Transglycosylase (TGase) is an attractive target for new antibiotic discovery due to its location on the outer membrane of bacteria and its essential role in peptidoglycan synthesis. Though there have been a few molecules identified as TGase inhibitors in the past thirty years, none of them have been developed into antibiotics for humans. The slow pace of development is perhaps due to the lack of continuous, quantitative, and high-throughput assay available for the enzyme. Herein, we report a new continuous fluorescent assay based on Förster resonance energy transfer, using lipid II analogues with a dimethylamino-azobenzenesulfonyl quencher in the lipid chain and a coumarin fluorophore in the peptide chain. During the process of transglycosylation, the quencher-appended polyprenol is released and the fluorescence of coumarin can be detected. Using this system, the substrate specificity and affinity of lipid II analogues bearing various numbers and configurations of isoprene units were investigated. Moreover, the inhibition constants of moenomycin and two previously identified small molecules were also determined. In addition, a high-throughput screening using the new assay was conducted to identify potent TGase inhibitors from a 120,000 compound library. This new continuous fluorescent assay not only provides an efficient and convenient way to study TGase activities, but also enables the high-throughput screening of potential TGase inhibitors for antibiotic discovery.

A useful method integrating production and immobilization of recombinant cellulase.

The development of cellulase-based bioprocess is afflicted by the processing efficiency of enzymes. To address this issue, a method based on artificial oil bodies (AOBs) was proposed to integrate production and immobilization of recombinant cellulase. First, the heterologous endoglucanase (celA), cellobiohydrolase (celK), and ß-glucosidase (gls) genes were individually fused with oleosin, a structural protein of plant seed oils. After expression in Escherichia coli, each fusion protein of insolubility was mixed together with plant oils. AOBs were assembled by subjecting the mixture to sonication. Consequently, active CelA, CelK, and Gls were resumed and co-immobilized on AOBs surface. Finally, the assembly condition (including the protein ratio) and the reaction condition were further optimized by response surface methodology. The resulting AOBs-bound cellulase remained stable for 4 cycles of cellulose-hydrolyzed reactions. Overall, the result shows a promise of this proposed approach for processing recombinant cellulase, which may provide a facile method to investigate optimum combination of cellulase components towards various cellulosic materials.

New 7-[4-(4-(un)substituted)piperazine-1-carbonyl]- piperazin-1-yl] derivatives of fluoroquinolone: synthesis and antimicrobial evaluation.

Fluoroquinolones have been a class of important synthetic antimicrobial agents broadly and effectively used in clinic for infectious diseases. In this study, the synthesis of a range of fluoroquinolone derivatives with 4-(carbopiperazin-1-yl)piperazinyl moieties at the C7 position and their inhibition of bacterial pathogens commonly disseminated in hospital environment were described. The results indicated that a 7-[4-(4-(benzoyl)carbopiperazin-1-yl)]piperazinyl derivative 5h and two 7-[4-(4- (benzenesulfonyl)carbopiperazin-1-yl)]piperazinyl derivatives 5k and 5l showed more promising growth inhibition of ciprofloxacin-resistant P. aeruginosa (CRPA) with MIC values as low as 16 µg/mL which is 16-fold more potent than ciprofloxacin, while most of other derivatives maintained potency against methicillin-resistant Staphylococcus aureus (MRSA).

Evaluation of You-Gui-Wan critical compounds inhibiting ALOX-5 and HDC gene expression in RBL-2H3 cells using a fractional factorial design.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine (TCM) You-Gui-Wan (YGW) has been used to treat asthma for hundreds of years. AIM OF THE STUDY: YGW is composed of 10 types of medicinal materials. However, the immune mechanism of YGW in asthma treatment has not been elucidated. Therefore, this study investigated asthma symptoms attenuated by YGW and the underlying immune regulatory mechanism. MATERIALS AND METHODS: Intratracheal (i.t.) stimulation of BALB/c mice with Dermatophagoides pteronyssinus (Der p) was performed once per week (40 µL, 2.5 µg/µL). For six consecutive weeks, different doses of YGW (0.2 g/kg and 0.5 g/kg) were orally administered 30 min before stimulation with Der p. After the last stimulation, airway hyperreactivity, lung gene expression, and total immunoglobulin E (IgE) in blood were evaluated using a whole-body plethysmograph system, real-time PCR, and ELISA, respectively. In addition, DNP-IgE/DNP-BSA was added to stimulate mast cells (RBL-2H3), and YGW or various compound compositions (Trial) were added to RBL-2H3 cells for 30 min to evaluate the effects of the drug on mast cell degranulation and on gene expression. JMP 5.1 software was used to design and analyze YGW's critical compounds by which it inhibited ALOX-5 and HDC gene expression in RBL-2H3 cells. RESULTS: YGW significantly decreased serum total IgE levels and airway hyperresponsiveness in asthmatic mice. YGW also reduced the gene expression of IL-6, TNF-α, IL-4, IL-13, and COX-2 in the lungs of asthmatic mice and RBL-2H3 cells. YGW and the compound (Trial 21) present in YGW inhibited the gene expression of ALOX-5 and HDC in RBL-2H3 cells. CONCLUSION: The experimental results indicate that YGW exhibits anti-airway hyperresponsiveness and specific immunomodulatory effects. In addition, YGW synergistically inhibits ALOX-5 and HDC gene expression in mast cells through a combination of 21 compounds, including luteolin, quercetin, and ß-carotene.