Efficacy of a Virtual 3D Simulation-Based Digital Training Module for Building Dental Technology Students' Long-Term Competency in Removable Partial Denture Design: Prospective Cohort Study.

Background: Removable partial denture (RPD) design is crucial to long-term success in dental treatment, but shortcomings in RPD design training and competency acquisition among dental students have persisted for decades. Digital production is increasing in prevalence in stomatology, and a digital RPD (D-RPD) module, under the framework of the certified Objective Manipulative Skill Examination of Dental Technicians (OMEDT) system reported in our previous work, may improve on existing RPD training models for students. Objective: We aimed to determine the efficacy of a virtual 3D simulation-based progressive digital training module for RPD design compared to traditional training. Methods: We developed a prospective cohort study including dental technology students at the Stomatology College of Chongqing Medical University. Cohort 1 received traditional RPD design training (7 wk). Cohort 2 received D-RPD module training based on text and 2D sketches (7 wk). Cohort 3 received D-RPD module pilot training based on text and 2D sketches (4 wk) and continued to receive training based on 3D virtual casts of real patients (3 wk). RPD design tests based on virtual casts were conducted at 1 month and 1 year after training. We collected RPD design scores and the time spent to perform each assessment. Results: We collected the RPD design scores and the time spent to perform each assessment at 1 month and 1 year after training. The study recruited 109 students, including 58 (53.2%) female and 51 male (56.8%) students. Cohort 1 scored the lowest and cohort 3 scored the highest in both tests (cohorts 1-3 at 1 mo: mean score 65.8, SD 21.5; mean score 81.9, SD 6.88; and mean score 85.3, SD 8.55, respectively; P<.001; cohorts 1-3 at 1 y: mean score 60.3, SD 16.7; mean score 75.5, SD 3.90; and mean score 90.9, SD 4.3, respectively; P<.001). The difference between cohorts in the time spent was not statistically significant at 1 month (cohorts 1-3: mean 2407.8, SD 1370.3 s; mean 1835.0, SD 1329.2 s; and mean 1790.3, SD 1195.5 s, respectively; P=.06) but was statistically significant at 1 year (cohorts 1-3: mean 2049.16, SD 1099.0 s; mean 1857.33, SD 587.39 s; and mean 2524.3, SD 566.37 s, respectively; P<.001). Intracohort comparisons indicated that the differences in scores at 1 month and 1 year were not statistically significant for cohort 1 (95% CI -2.1 to 13.0; P=.16), while cohort 3 obtained significantly higher scores 1 year later (95% CI 2.5-8.7; P=.001), and cohort 2 obtained significantly lower scores 1 year later (95% CI -8.8 to -3.9; P<.001). Conclusions: Cohort 3 obtained the highest score at both time points with retention of competency at 1 year, indicating that progressive D-RPD training including virtual 3D simulation facilitated improved competency in RPD design. The adoption of D-RPD training may benefit learning outcomes.

Global gene expression profiling of perirenal brown adipose tissue whitening in goat kids reveals novel genes linked to adipose remodeling.

BACKGROUND: Brown adipose tissue (BAT) is known to be capable of non-shivering thermogenesis under cold stimulation, which is related to the mortality of animals. In the previous study, we observed that goat BAT is mainly located around the kidney at birth, and changes to white adipose tissue (WAT) in the perirenal adipose tissue of goats within one month after birth. However, the regulatory factors underlying this change is remain unclear. In this study, we systematically studied the perirenal adipose tissue of goat kids in histological, cytological, and accompanying molecular level changes from 0 to 28 d after birth. RESULTS: Our study found a higher mortality rate in winter-born goat kids, with goat birthing data statistics. Then we used thermal imaging revealing high temperature in goat hips at postnatal 0 d and gradually decrease during 28 d. This is consistent with the region of perirenal BAT deposition and highlights its critical role in energy expenditure and body temperature regulation in goat kids. Additionally, we found a series of changes of BAT during the first 28 d after birth, such as whitening, larger lipid droplets, decreased mitochondrial numbers, and down-regulation of key thermogenesis-related genes (UCP1, DIO2, UCP2, CIDEA, PPARGC1a, C/EBPb, and C/EBPa). Then, we used RNA-seq found specific marker genes for goat adipose tissue and identified 12 new marker genes for BAT and 10 new marker genes for WAT of goats. Furthermore, 12 candidate genes were found to potentially regulate goat BAT thermogenesis. The mechanism of the change of this biological phenomenon does not involve a large-scale death of brown adipocytes and subsequent proliferation of white adipocytes. While apoptosis may play a limited role, it is largely not critical in this transition process. CONCLUSIONS: We concluded that perirenal BAT plays a crucial role in thermoregulation in newborn goat kids, with notable species differences in the expression of adipose tissue marker genes, and we highlighted some potential marker genes for goat BAT and WAT. Additionally, the change from BAT to WAT does not involve a large-scale death of brown adipocytes and subsequent proliferation of white adipocytes.

Loss of AR-regulated AFF3 contributes to prostate cancer progression and reduces ferroptosis sensitivity by downregulating ACSL4 based on single-cell sequencing analysis.

Prostate cancer (PCa) is one of the most common cancers affecting the health of men worldwide. Castration-resistant prostate cancer (CRPC), the advanced and refractory phase of prostate cancer, has multiple mechanisms of resistance to androgen deprivation therapy (ADT) such as AR mutations, aberrant androgen synthase, and abnormal expression of AR-related genes. Based on the research of the AR pathway, new drugs for the treatment of CRPC have been developed in clinical practice, such as Abiraterone and enzalutamide. However, many areas in this pathway are still worth exploring. In this study, single-cell sequencing analysis was utilized to scrutinize significant genes in the androgen receptor (AR) pathway related to CRPC. Our analysis of single-cell sequencing combined with bulk-cell sequencing revealed a substantial downregulation of AR-regulated AFF3 in CRPC. Overexpression of AFF3 restricted the proliferation and migration of prostate cancer cells whilst also increasing their sensitivity towards enzalutamide, while knockdown of AFF3 had the opposite effect. To elucidate the mechanism of tumor inhibition by AFF3, we applied GSVA and GSEA to investigate the metabolic pathways related to AFF3 and revealed that AFF3 had an impact on fatty acids metabolism and ferroptosis through the regulation of ACSL4 protein expression. Based on correlation analysis and flow cytometry, we can speculate that AFF3 can impact the sensitivity of the CRPC cell lines to the ferroptosis inducer (RSL3) by regulating ACSL4. Therefore, our findings may provide new insights into the mechanisms of drug resistance in CRPC, and AFF3 may serve as a novel prognostic biomarker in prostate cancer.

Rab5c promotes RSV and ADV replication by autophagy in respiratory epithelial cells.

Respiratory system diseases caused by respiratory viruses are common and exert tremendous pressure on global healthcare system. In our previous studies, we found that Long non-coding RNA NRAV (Lnc NRAV) and its target molecule Rab5c plays a significant role in respiratory virus infection. However, the mechanism by which Rab5c affects virus replication remains unclear. Rab5c, a protein mainly localized on the cell membranes and in early endosomes and phagosomes, participates in endocytosis mediated by clathrin and regulates the fusion of early endosome, maturation of early phagosomes, and autophagy. Therefore, we inferred that Rab5c impacts virus replication, which might be related to endocytosis or autophagy. We selected RSV (respiratory syncytial virus) as a representative enveloped virus and ADV (Adenovirus) as a representative non-enveloped virus to explore the possible mechanism of RSV and ADV replication promoted by Rab5c in A549 cells and in Rab5c-overexpressing mice. Here, we confirmed that the activated Rab5c promotes RSV and ADV replication and the inactivated Rab5c inhibits their replication. However, Rab5c promoting RSV and ADV replication is not mediated by endocytosis rather by autophagy in respiratory epithelial cells. Our study showed that Rab5c upregulates LC3-Ⅱ (microtubule-associated protein 1 light chain 3 beta) protein expression levels by interacting with Beclin1, a key autophagy molecule, which can induce autophagy and promote replication of ADV and RSV. This study enriches the understanding of the interaction between respiratory viruses and Rab5c, providing new insights for virus prevention and treatment.

Percutaneous Ultrasound Cholangiography With Microbubbles in Children With Biliary Diseases.

ABSTRACT: The application of intracavity contrast-enhanced ultrasound in the evaluation of biliary disease has been confirmed valuable among pediatric population. This pictorial essay aims to demonstrate the role of percutaneous ultrasound cholangiography (PUSC) with microbubbles in the diagnosis of different pediatric biliary diseases in our center. The biliary system's morphologic characteristics in PUSC mode of neonatal hepatitis, biliary atresia, choledochal cysts, and biliary complications of hepatobiliary surgery are presented.

Genome-Wide Association Study of the Reproductive Traits of the Dazu Black Goat (Capra hircus) Using Whole-Genome Resequencing.

Reproductive traits are the basic economic traits of goats and important indicators in goat breeding. In this study, Dazu black goats (DBGs; n = 150), an important Chinese local goat breed with excellent reproductive performance, were used to screen for important variation loci and genes of reproductive traits. Through genome-wide association studies (GWAS), 18 SNPs were found to be associated with kidding traits (average litter size, average litter size in the first three parity, and average litter size in the first six parity), and 10 SNPs were associated with udder traits (udder depth, teat diameter, teat length, and supernumerary teat). After gene annotation of the associated SNPs and in combination with relevant references, the candidate genes, namely ATP1A1, LRRC4C, SPCS2, XRRA1, CELF4, NTM, TMEM45B, ATE1, and FGFR2, were associated with udder traits, while the ENSCHIG00000017110, SLC9A8, GLRB, GRIA2, GASK1B, and ENSCHIG00000026285 genes were associated with litter size. These SNPs and candidate genes can provide useful biological information for improvement of the reproductive traits of goats.

Predictive model containing gene signature and shear wave elastography to predict patient outcomes after Kasai surgery in biliary atresia.

AIMS: Infants with biliary atresia (BA) are treated with Kasai portoenterostomy (KPE) surgery, but many BA patients need subsequent salvage liver transplants. The aim of this study is to develop a comprehensive gene-clinical model based on two-dimensional shear wave elastography (2DSWE), liver gene expression, and other clinical parameters to predict response to KPE for BA patients. METHODS: Differentially expressed gene patterns between liver samples of BA (n = 102) and non-BA control (n = 14) were identified using RNA sequencing analysis. Biliary atresia patients were then randomly assigned to training and validation cohorts. Gene classifier based on the differentially expressed genes was built in the training cohort. Nomogram models with and without gene classifier were further constructed and validated for predicting native liver survival of BA patients. The utility of the nomograms was compared by C-index. RESULTS: Using the least absolute shrinkage and selection operator model, we generated a nine-gene prognostic classifier. The nomogram based on the nine-gene classifier, age, preoperative 2DSWE, and albumin had the better C-index compared to gene classifier alone in the training cohort (0.83 [0.76-0.90] vs. 0.69 [0.61-0.77], p = 0.003) and the validation cohort (0.74 [0.67-0.82] vs. 0.62 [0.55-0.70], p = 0.001). Using risk scores developed from the nomogram, the 12-month survival rates of BA patients with native liver were 35.7% (95% confidence interval [CI], 22.7-56.3) in the high-risk group and 80.8% (95% CI, 63.4-100.0) in the low-risk group in the validation cohort. CONCLUSIONS: The comprehensive genetic-clinical nomogram based on preoperative 2DSWE, liver gene expression, and other clinical parameters can accurately predict response to KPE.

Special NaBH4 hydrolysis achieving multiple-surface-modifications promotes the high-throughput water oxidation of CoN nanowire arrays.

Designing an excellent OER catalyst in an alkaline environment is severe yet essential for industrial H2 application under the electrochemical technique. This study has achieved multiple modifications on CoN nanowires, the classic OER catalyst, via a facile room-temperature NaBH4 spontaneous hydrolysis. This facile process simultaneously generates oxygen vacancies and robust BN species. It wraps hydrophilic BOx motifs on the OER response CoN nanowires, producing OER active Co-N-B species, increasing active numbers and guaranteeing structural stability. It suggests that a low NaBH4 concentration (0.1 mol L-1) treatment endows CoNNWAs/CC with excellent OER performance and robust structure, which can drive a current density of 50 mA cm-2 with only 325 mV overpotentials with more than 24 hours' durability. Even, the catalyst can drive 1000 mA cm-2 around 480 mV overpotential. This study allows a novel strategy for designing high-performance OER catalysts.

Utility of the pediatric liver contrast-enhanced ultrasound criteria in differentiating malignant and benign multifocal lesions.

BACKGROUND: The pediatric liver contrast-enhanced ultrasound (CEUS) criteria were developed to improve the diagnostic performance of CEUS in differentiating pediatric benign and malignant liver lesions. However, the diagnostic performance of CEUS in the evaluation of multiple focal liver lesions in the pediatric population has not yet been fully evaluated. OBJECTIVE: To evaluate the diagnostic performance of the pediatric liver CEUS criteria in differentiating benign and malignant multifocal liver lesions in children. MATERIALS AND METHODS: From April 2017 to September 2022, the CEUS characteristics of multifocal liver lesions in patients < 18 years were analyzed. Lesions classified as CEUS-1, CEUS-2 or CEUS-3 were considered benign and lesions classified as CEUS-4 or CEUS-5 were considered malignant. The diagnostic performance of the pediatric liver CEUS criteria (i.e. sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV] and accuracy) was assessed. RESULTS: After exclusion, 21 patients (median age, 36.0 months; range, 1.0-204 months; 7 boys) were included. There were significant differences in the serum alpha fetoprotein level (P= 0.039) and the presence of washout (P < 0.001) between children with malignant and benign lesions. The sensitivity, specificity, PPV, NPV and accuracy of the pediatric liver CEUS criteria were 100.0% (10/10), 90.9% (10/11), 90.9% (10/11), 100.0% (10/10) and 95.2% (20/21), respectively. CONCLUSION: The pediatric liver CEUS criteria had excellent diagnostic performance in differentiating benign and malignant multifocal liver lesions in children.

Association analysis of polymorphisms at GLRB, GRIA2, and GASK1B genes with reproductive traits in Dazu Black Goats.

Reproductive traits are essential economic traits in goats. This study aimed to analyze the relationship between single nucleotide polymorphisms (SNPs) within the genes of GLRB, GRIA2, and GASK1B, and reproductive traits (kidding traits and placental traits) in goats. We used the resequencing data of 150 Dazu Black Goats to perform correlation analysis with the average litter size. We screened thirteen SNPs loci in introns and then used the Sanger method to genotype the remaining 150 Dazu Black Goats. The results showed that a total of six SNPs were screened. Three SNPs related to litter size and live litter size (g.28985790T > G, g.28986352A > G, and g.28987976A > G); one SNP related to total cotyledon area (g.29203243G > A); two SNPs related to placental efficiency (g.30189055G > A and g.30193974C > T); one SNP associated with cotyledon support efficiency (g.30193974C > T). The qPCR results showed that GLRB, GRIA2, and GASK1B were all highly expressed in the udder, kidney, uterus, and ovary. It indicated that these three candidate genes might affect the reproductive traits, which could be used as candidate markers for reproductive traits in Dazu Black Goats. Moreover, association studies on a large scale are still needed to figure out what effect these SNPs have on reproductive traits.

Diagnostic accuracy of the 4AT for delirium: A systematic review and meta-analysis.

INTRODUCTION: Despite common, serious, costly, and often fatal conditions affecting up to 50 % of older patients, delirium is often unrecognized and overlooked. We examine the accuracy of the 4AT for detecting older patients with delirium. METHODS: We performed a systematic search of PubMed, Web of Science, PsycINFO, and EMBASE databases from inception to April 2020 and updated to January 2022. Four independently reviewers extracted study data and assessed the methodological quality using the revised quality assessment of diagnostic accuracy studies tool (QUADAS-2). Pooled estimates of sensitivity and specificity were generated using a bivariate random effects model. All statistical analyses were performed with STATA version 15.1 and Meta-DiSc version 1.4 software. RESULTS: Eleven studies with 2789 participants were included. The pooled sensitivity and specificity were 0.87 (95 % CI: 0.81-0.91) and 0.87 (95 % CI: 0.79-0.92), respectively, and the positive and negative likelihood ratios were 6.66 (95 % CI: 4.12-10.74) and 0.15 (95 % CI: 0.10-0.23), respectively. Deeks' test indicated no significant publication bias (t = 0.83, P = 0.43). Univariable meta-regression showed that patient selection and flow and timing significantly influenced the pooled sensitivity (P < 0.05), settings significantly influenced the pooled specificity (P < 0.05). CONCLUSION: Our meta-analysis demonstrates that 4AT is a sensitive and specific screening tool for delirium in older patients. Its brevity and simplicity support its use in routine clinical practice, particularly in time-poor settings. Clinicians should come to a conclusion based largely on the 4AT findings in conjunction with clinical judgment.

Smoking Status Modifies the Relationship between Th2 Biomarkers and Small Airway Obstruction in Asthma.

Background: Cigarette smoking and Th2-inflammation are both crucial in the pathogenesis of asthma. However, it is unknown whether smoking can affect the association between Th2-inflammation and small airway obstruction in adults with asthma. Methods: Adults diagnosed with asthma by a pulmonologist according to Global Initiative for Asthma guidelines were recruited from September 2016 to April 2018 to participate in this study. Participants were divided into two groups, the small airway obstruction group (those with FEF25-75% predicted value ≤ 65%) and the normal small airway function group (those with FEF25-75% predicted value > 65%). Final data analysis included 385 and 93 people in the Obstructive Group and the Normal Group, respectively. Total serum IgE level and blood eosinophil count were used as biomarkers of the Th2 phenotype. Results: The Obstructive Group had a larger fraction of smokers, higher blood eosinophil count, and lower lung function than the Normal Group. Current-smoking status was associated with an increased risk of small airway obstruction (adjusted odds ratio = 4.677, 95% confidence interval [1.593-13.730]); and log-IgE level was associated with a decreased risk of small airway obstruction (0.403 [0.216-0.754]). Smoking status stratified analysis showed an association between log-IgE level and a decreased risk of small airway obstruction only in never-smoker asthmatics (0.487 [0.249-0.954]). Conclusions: Current-smoking status and total serum IgE are, respectively, associated with small airway obstruction. Smoking status modifies the relationship between Th2 biomarkers and small airway function. These findings contribute to the understanding of risk factors associated with asthma endotyping.

National trends in population rates of opioid-related mortality, hospitalization and emergency department visits in Canada between 2000 and 2017. A population-based study.

BACKGROUND AND AIMS: Existing assessments of the time-trends of opioid-related mortality, hospitalization and emergency department visits in Canada have relied mainly on provincial databases, while national assessments generally do not provide information before 2016. We aimed to estimate Canadian national time trends in opioid-related mortality from 2000 to 2017 and opioid-related hospitalization and emergency department visits between 2000 and 2012. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Residents of all Canadian provinces and territories for which comparable data were available from 2000 to 2017. MEASUREMENTS: We identified opioid-related mortality, hospitalization and emergency department visits using validated algorithms using ICD codes from administrative databases. We calculated crude rates and sex- and age-adjusted rates per million. For hospitalizations, we calculated case-fatality, 90-day and 365-day all-cause mortality and opioid-related re-hospitalization rates. We used Poisson regression to examine the significance of the time trend. FINDINGS: From 2000 to 2017, the adjusted opioid mortality rate in Canada (outside Quebec) increased significantly by 592.9% (from 20.0 opioid deaths per million in 2000 to 118.3 in 2017). The highest year-to-year increases were from 2015 to 2016 (31.8%) and from 2016 to 2017 (52.2%). The adjusted hospitalizations doubled significantly during the study period (an increase of 103.7%, from 159.7 opioid hospitalizations per million Canadians in 2000 to 325.3 in 2012). The adjusted rate of emergency department visits increased significantly by 188.7% (from 280.6 per million in 2000 to 810.1 in 2012). Case-fatality was 2.3% overall and was mainly constant during the study period. Both 90- and 365-day all-cause mortality increased significantly between 2000 and 2011 (from 1.7 to 3.1% and 3.9 to 7.4%, respectively), while re-hospitalization for opioid-related diagnoses was reduced (from 7.8 to 6.4% and 14.2 to 12.9%, respectively). CONCLUSIONS: Opioid-related mortality, hospitalization and emergency department visits in Canada have been increasing gradually since 2000.

Delirium screening tools in the emergency department: A protocol for systematic review and meta-analysis.

BACKGROUND: Delirium is a common type of acute brain dysfunction among emergency department (ED) patients. The prevalence of delirium in the ED is up to 40%. Although screening instruments used to identify delirium have been developed, it is unclear which tool is the most accurate in the ED. To address this challenging, we systematically examine the accuracy of delirium screening tools used to assess the ED patients. METHODS: This study has been registered at the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY), and the registration number is INPLASY202110041. We will search the PubMed, EMBASE, PsycINFO, and the Cochrane Library. Studies involving patients which compared diagnostic instruments with the criteria in Diagnostic and Statistical Manual of Mental Disorders (DSM) as a reference standard will be included. We will use STATA 15.1 and MetaDiSC to make careful analysis of the results. The quality of included studies will be assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 scale. RESULTS: In this study, the accuracy of different screening methods among ED patients is assessed by a high-quality synthesis. The number of tools available for screening delirium in the ED, the information of studies including the countries, the study design, the sample size and the characteristic of studies, the quality of the studies and the results of meta-analysis. The systematic review and meta-analysis will be published in a peer-reviewed journal. CONCLUSION: According to the conclusion of the systematic review, evidence will be provided to judge which screening method is the best for the ED patients. The results will bring better understanding of screening methods in the ED and highlight gaps for future research.

Delirium screening tools: A protocol for a systematic review and meta-analysis.

BACKGROUND: Delirium is a frequent form of acute brain dysfunction in mechanically ventilated patients. Screening tools have been developed to identify delirium, but it is unclear which tool is the most accurate. Therefore, we provide a protocol of systematic evaluation to assess the accuracy of delirium screening tools in mechanically ventilated patients. METHODS: PubMed, PsycINFO, EMBASE, and the Cochrane Library will be searched. Studies involving mechanically ventilated patients which compared diagnostic tools with the Diagnostic and Statistical Manual of Mental Disorders criteria as a reference standard will be included. We will use MetaDiSC and STATA 15.1 to analyze carefully when a network meta-analysis is allowed. RESULTS: This study will provide a high-quality synthesis to assess the accuracy of different screening methods in mechanically ventilated patients. CONCLUSION: The conclusion of our systematic review will provide evidence to judge which screening method is the best for mechanically ventilated patients.

Fixed Ratio Versus Lower Limit of Normal: Health Status and Risk Factors for COPD Overdiagnosis.

BACKGROUND: The threshold of the lower limit of the normal range of lung function has been suggested to be more accurate than the 0.7 fixed ratio (FEV1/FVC < 0.7) for a diagnosis of COPD. We aimed to explore the health status and risk factors of patients overdiagnosed with COPD when using the lower limit of the normal range as a diagnostic reference. METHODS: Subjects with COPD diagnosed by a pulmonologist according to guidelines of the Global Initiative for Chronic Obstructive Lung Disease were recruited from October 2016 to April 2018. Overdiagnosed COPD was defined as FEV1/FVC that meets the criterion of the 0.7 fixed ratio but not the the lower limit of the normal range criterion. Spirometry and questionnaires were performed by eligible subjects. RESULTS: Of the 513 subjects included in the final analysis, 20 (3.9%) were overdiagnosed when using the lower limit of the normal range as the diagnostic reference. The subjects who were overdiagnosed were older, weighed more, had better lung function, lower modified Medical British Research Council scores, and higher St. George's Respiratory Questionnaire and 36-item Short Form Survey scores than the subjects who were correctly diagnosed. Older age, heavier weight, exposure to cooking oil fumes, or a new-built or newly renovated home were associated with an increased risk of overdiagnosis of COPD (age adjusted odds ratio (OR) 1.17, 95% CI 1.09-1.26; weight adjusted OR 1.08, 95% CI 1.03-1.13; exposure to cooking oil fumes adjusted OR 3.00, 95% CI, 1.04-8.68; exposure to new-built or newly renovated home adjusted OR 10.88, 95% CI 1.46-80.87. CONCLUSIONS: The subjects with overdiagnosed COPD had a better health status and lung function than the subjects who were correctly diagnosed. Older age, heavier weight, and exposure to cooking oil fumes or a new-built or newly renovated home were factors associated with the overdiagnosis of COPD. These findings may help reduce overdiagnosis of COPD.

Airway reversibility in asthma and phenotypes of Th2-biomarkers, lung function and disease control.

BACKGROUND: High bronchodilator reversibility in adult asthma is associated with distinct clinical characteristics. In this study, we aim to make a comparison with T-helper 2 (Th2)-related biomarkers, lung function and asthma control between asthmatic patients with high airway reversibility (HR) and low airway reversibility (LR). METHODS: Patients with asthma diagnosed by pulmonologist according to Global Initiative for Asthma guidelines were recruited from the outpatient department of our hospital from August 2014 to July 2017. Patients were divided into HR and LR subgroups based on their response to bronchodilators of lung function (HR = Δforced expiratory volume in one second (FEV1) postbronchodilator ≥ 20%). Blood eosinophil count and serum IgE level, which are biomarkers of T-helper (Th)-2 phenotypes, were detected for patients. Asthma Control Test (ACT) was used to assess asthma control after the first-month initial treatment. RESULTS: A total of 265 patients with asthma were followed 1 month after initial treatment. HR group shows a higher level of Th2-high biomarkers (blood eosinophil count (10^9/L): 0.49 ± 0.28 vs 0.36 ± 0.19, P < 0.01; IgE (ng/ml): 1306 ± 842 vs 413 ± 261, P < 0.01), lower baseline lung function (FEV1%pred: 51.91 ± 19.34% vs 60.42 ± 19.22%, P < 0.01; forced expiratory flow (FEF)25-75: 0.76 ± 0.37 vs 1.00 ± 0.67, P < 0.01; FEF25-75%pred: 21.15 ± 10.09% vs 29.06 ± 16.50%, P < 0.01), and better asthma control (ACT score: 22 ± 4 vs 20 ± 4, P = 0.01) than LR group. HR was associated with a decreased risk of uncontrolled asthma after the first-month initial treatment (adjusted OR: 0.12 [95% confidence intervals: 0.03-0.50]). CONCLUSIONS: HR is a physiologic indicator of lower lung function and severer small airway obstruction, and is more related with an increased level of Th2-biomarkers than LR. Moreover, HR may indicate controlled asthma after the first-month initial treatment. This finding may contribute to identification of asthma endotype.

[Effect of triptolide on airway smooth muscle proliferation and the expression of nuclear factor-kappa B, Bcl-2 in asthmatic rats].

OBJECTIVE: To explore the effect of triptolide on airway remodeling and the expression of nuclear factor-kappaB, Bcl-2 in asthmatic rats. METHODS: 40 rats were randomly divided into 5 groups (n = 8): (1) Control group; (2) Asthmatic 4 week group; (3) Asthmatic 6 week group; (4) Therapeutic 4 week group; (5) Therapeutic 6 week group. The airway resistance and eosinophilic inflammation of airway wall were observed. The airway wall thickness (WA/Pi), the bronchial smooth muscle thickness (smooth muscle area/Pi) and the number of bronchial smooth muscle nucleus (N/Pi) were measured by image analysis system. The expression of PCNA, nuclear factor-kappaB and Bcl-2 protein were determined by immunohistochemical staining and Western blot. The expression of Bcl-2 mRNA was determined by reverse transcription-polymerase chain reaction(RT-PCR). RESULTS: (1) The expression of NF-kappaB protein in asthmatic 4 week group and asthmatic 6 week group was significantly higher than that in control group, respectively (P < 0.01). The above-mentioned parameters of therapeutic 6 week group were significantly lower than those of asthmatic 4 week group, asthmatic 6 week group and therapeutic 4 week group, respectively (P < 0.01, P < 0.01 P < 0.05). (2) The expression of Bcl-2 protein and mRNA of asthmatic 4 week group and asthmatic 6 week group were significantly higher than those in control group respectively (P < 0.01). The expression of Bcl-2 protein of therapeutic 6 week group was significantly lower than those of asthmatic 4 week group, asthmatic 6 week group and therapeutic 4 week group respectively (P < 0.05, P < 0.01, P < 0.01), but the expression of Bcl-2 mRNA was significantly higher than the above-mentioned groups respectively (P < 0.01), the expression of Bcl-2 protein and mRNA of therapeutic 6 week group were higher than control group respectively (P < 0.05, P < 0.01). (3) The expression of PCNA protein of asthmatic 4 week group and asthmatic 6 week group were significantly higher than those of control group respectively (P < 0.01). (4) The WA/ Pi, the smooth muscle area/Pi and the N/Pi of asthmatic 4 week group and asthmatic 6 week group were significantly higher than those of control group, respectively (P < 0.01). The above-mentioned parameters of therapeutic 6 week group were significantly lower than those of asthmatic 4 week group, asthmatic 6 week group and therapeutic 4 week group, respectively (P < 0.01). (5) The airway resistance of asthmatic 4 week group and asthmatic 6 week group were significantly higher than those of the control group, respectively (P < 0.01). The above-mentioned parameters of therapeutic 6 week group were significantly lower than those of asthmatic 4 week group, asthmatic 6 week group and therapeutic 4 week group, respectively (P < 0.01, P < 0.01, P < 0.05). CONCLUSION: The proliferation of airway smooth muscle(ASM) is related with apoptosis of airway smooth muscle cells in asthma. NF-kappaB may be involved in the process. Triptolide may prevent apoptosis of ASMCs and decrease the proliferation of ASM by inhibiting the expression of NF-kappaB, Bcl-2.