Improving multi-population genomic prediction accuracy using multi-trait GBLUP models which incorporate global or local genetic correlation information.

In the application of genomic prediction, a situation often faced is that there are multiple populations in which genomic prediction (GP) need to be conducted. A common way to handle the multi-population GP is simply to combine the multiple populations into a single population. However, since these populations may be subject to different environments, there may exist genotype-environment interactions which may affect the accuracy of genomic prediction. In this study, we demonstrated that multi-trait genomic best linear unbiased prediction (MTGBLUP) can be used for multi-population genomic prediction, whereby the performances of a trait in different populations are regarded as different traits, and thus multi-population prediction is regarded as multi-trait prediction by employing the between-population genetic correlation. Using real datasets, we proved that MTGBLUP outperformed the conventional multi-population model that simply combines different populations together. We further proposed that MTGBLUP can be improved by partitioning the global between-population genetic correlation into local genetic correlations (LGC). We suggested two LGC models, LGC-model-1 and LGC-model-2, which partition the genome into regions with and without significant LGC (LGC-model-1) or regions with and without strong LGC (LGC-model-2). In analysis of real datasets, we demonstrated that the LGC models could increase universally the prediction accuracy and the relative improvement over MTGBLUP reached up to 163.86% (25.64% on average).

Factors influencing postoperative visual improvement in 208 patients with tuberculum sellae meningiomas.

OBJECTIVE: Tuberculum sellae meningiomas (TSMs) usually compress the optic nerve and optic chiasma, thus affecting vision. Surgery is an effective means to remove tumors and improve visual outcomes. On a larger scale, this study attempted to further explore and confirm the factors related to postoperative visual outcomes to guide the treatment of TSMs. METHODS: Data were obtained from 208 patients with TSMs who underwent surgery at our institution between January 2010 and August 2022. Demographics, ophthalmologic examination results, imaging data, extent of resection, radiotherapy status, and surgical approaches were included in the analysis. Univariate and multivariate logistic regressions were used to assess the factors that could lead to favorable visual outcomes. RESULTS: The median follow-up duration was 63 months, and gross total resection (GTR) was achieved in 174 (83.7%) patients. According to our multivariate logistic regression analysis, age < 60 years (odds ratio [OR] = 0.310; P = 0.007), duration of preoperative visual symptoms (DPVS) < 10 months (OR = 0.495; P = 0.039), tumor size ≤ 27 mm (OR = 0.337; P = 0.002), GTR (OR = 3.834; P = 0.006), and a tumor vertical-to-horizontal dimensional ratio < 1 (OR = 2.593; P = 0.006) were found to be significant independent predictors of favorable visual outcomes. CONCLUSION: Age, DPVS, tumor size, GTR, and the tumor vertical-to-horizontal dimensional ratio were found to be powerful predictors of favorable visual outcomes. This study may help guide decisions regarding the treatment of TSMs.

Small DNAs That Specifically and Tightly Bind Transition Metal Ions.

Specific DNA-binding to metal ions is a long-standing fundamental research topic with great potential to transform into nano/biotechnology and therapeutics applications. Herein, based on the mobility change of DNA in denaturing gels, we develop a selection strategy to discover a series of 40-45 nt small DNAs that can bind Zn2+ and Cd2+ specifically and tightly. The Zn2+- and Cd2+-bound DNA complexes can even tolerate harsh denaturing conditions of 8 M urea and 50 mM EDTA. The discovery not only exposes a new class of transition metal ion-binding DNAs but also provides potentially a new tool for targeting drug therapies based on metal ions.

A Membrane Tension-Responsive Mechanosensitive DNA Nanomachine.

Membrane curvature reflects physical forces operating on the lipid membrane, which plays important roles in cellular processes. Here, we design a mechanosensitive DNA (MSD) nanomachine that mimics natural mechanosensitive PIEZO channels to convert the membrane tension changes of lipid vesicles with different sizes into fluorescence signals in real time. The MSD nanomachine consists of an archetypical six-helix-bundle DNA nanopore, cholesterol-based membrane anchors, and a solvatochromic fluorophore, spiropyran (SP). We find that the DNA nanopore effectively amplifies subtle variations of the membrane tension, which effectively induces the isomerization of weakly emissive SP into highly emissive merocyanine isomers for visualizing membrane tension changes. By measuring the membrane tension via the fluorescence of MSD nanomachine, we establish the correlation between the membrane tension and the curvature that follows the Young-Laplace equation. This DNA nanotechnology-enabled strategy opens new routes to studying membrane mechanics in physiological and pathological settings.

Programmable Assembly of Amphiphilic DNA through Controlled Cholesterol Stacking.

The excellent programmability and modifiability of DNA has enabled chemists to reproduce a series of specific molecular interactions in self-assembled synthetic systems. Among diverse modifications, cholesterol conjugation can turn DNA into an amphiphilic molecule (cholesterol-DNA), driving the formation of DNA assemblies through the cholesterol-endowed hydrophobic interaction. However, precise control of such an assembly process remains difficult because of the unbiased accumulation of cholesterol. Here, we report the serendipitous discovery of the favored tetramerization of cholesterol in cholesterol-DNA copolymers that carry the cholesterol modification at the blunt end of DNA. The discovery expands the repertoire of controllable molecular interactions by DNA and provides an effective way to precisely control the hydrophobic stacking of cholesterol for programmed cholesterol-DNA assembly.

MEScan: a powerful statistical framework for genome-scale mutual exclusivity analysis of cancer mutations.

MOTIVATION: Cancer somatic driver mutations associated with genes within a pathway often show a mutually exclusive pattern across a cohort of patients. This mutually exclusive mutational signal has been frequently used to distinguish driver from passenger mutations and to investigate relationships among driver mutations. Current methods for de novo discovery of mutually exclusive mutational patterns are limited because the heterogeneity in background mutation rate can confound mutational patterns, and the presence of highly mutated genes can lead to spurious patterns. In addition, most methods only focus on a limited number of pre-selected genes and are unable to perform genome-wide analysis due to computational inefficiency. RESULTS: We introduce a statistical framework, MEScan, for accurate and efficient mutual exclusivity analysis at the genomic scale. Our framework contains a fast and powerful statistical test for mutual exclusivity with adjustment of the background mutation rate and impact of highly mutated genes, and a multi-step procedure for genome-wide screening with the control of false discovery rate. We demonstrate that MEScan more accurately identifies mutually exclusive gene sets than existing methods and is at least two orders of magnitude faster than most methods. By applying MEScan to data from four different cancer types and pan-cancer, we have identified several biologically meaningful mutually exclusive gene sets. AVAILABILITY AND IMPLEMENTATION: MEScan is available as an R package at https://github.com/MarkeyBBSRF/MEScan. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Water-Dispersible Gold Nanoclusters: Synthesis Strategies, Optical Properties, and Biological Applications.

Atomically precise gold nanoclusters (AuNCs) are an emerging class of quantum-sized nanomaterials. Intrinsic discrete electronic energy levels have endowed them with fascinating electronic and optical properties. They have been widely applied in the fields of optoelectronics, photovoltaics, catalysis, biochemical sensing, bio-imaging, and therapeutics. Nevertheless, most AuNCs are synthesized in organic solvents and do not disperse in aqueous solutions; this restricts their biological applications. In this review, we focus on the recent progress in the preparation of water-dispersible AuNCs and their biological applications. We first review different methods of synthesis, including direct synthesis from hydrophilic templates and indirect phase transfer of hydrophobic AuNCs. We then discuss their photophysical properties, such as emission enhancement and fluorescence lifetimes. Next, we summarize their latest applications in the fields of biosensing, biolabeling, and bioimaging. Finally, we outline the challenges and potential for the future development of these AuNCs.

DNA-Encoded Gold-Gold Wettability for Programmable Plasmonic Engineering.

Controlling the deposition and diffusion of adsorbed atoms (adatoms) on the surface of a solid material is vital for engineering the shape and function of nanocrystals. Here, we report the use of single-stranded DNA (oligo-adenine, oligo-A) to encode the wettability of gold seeds by homogeneous gold adatoms to synthesize highly tunable plasmonic nanostructures. We find that the oligo-A attachment transforms the nanocrystal growth mode from the classical Frank-van der Merwe to the Volmer-Weber island growth. Finely tuning the oligo-A density can continuously change the gold-gold contact angle (θ) from 35.1±3.6° to 125.3±8.0°. We further demonstrate the versatility of this strategy for engineering nanoparticles with different curvature and dimensions. With this unconventional growth mode, we synthesize a sub-nanometer plasmonic cavity with a geometrical singularity when θ>90°. Superfocusing of light in this nanocavity produces a near-infrared intraparticle plasmonic coupling, which paves the way to surface engineering of single-particle plasmonic devices.

Near-field probing of dielectric screening by hexagonal boron nitride in graphene integrated on silicon photonics.

Hexagonal boron nitride (hBN) is one of the most suitable 2D materials for supporting graphene in electronic devices, and it plays a fundamental role in screening out the effect of charge impurities in graphene in contrast to inhomogeneous supports such as silicon dioxide (SiO2). Although many interesting surface science techniques such as scanning tunneling microscopy (STM) revealed dielectric screening by hBN and emergent physical phenomena were observed, STM is only appropriate for graphene electronics. In this paper, we demonstrate the dielectric screening by hBN in graphene integrated on a silicon photonic waveguide from the perspective of a near-field scanning optical microscopy (NSOM) and Raman spectroscopy. We found shifts in the Raman spectra and about three times lower slope decrease in the measured electric near-field amplitude for graphene on hBN relative to that for graphene on SiO2. Based on finite-difference time-domain simulations, we confirm lower electric field slope and scattering rate in graphene on hBN, which implies dielectric screening, in agreement with the NSOM signal. Graphene on hBN integrated on silicon photonics can pave the way for high-performance hybrid graphene photonics.

Cathelicidin aggravates myocardial ischemia/reperfusion injury via activating TLR4 signaling and P2X7R/NLRP3 inflammasome.

AIMS: The antimicrobial peptide cathelicidin (Camp) has multifunctional immunomodulatory activities. However, its roles in inflammation-related myocardial ischemia/reperfusion (MI/R) injury remain unclear. METHODS AND RESULTS: In this study, adult male C57BL/6 wild-type (WT) mice were subjected to MI/R injury by left anterior descending coronary artery ligation for 45 min followed by 3 or 24 h of reperfusion. An abundant cardiac expression of cathelicidin was observed during ischemia and reperfusion, which was mainly derived from heart-infiltrating neutrophils. Knockout of Camp in mice reduced MI/R-induced myocardial inflammation, infarct size, and circulating cTnI levels (an indicator of heart damage). CRAMP (the mature form of murine cathelicidin) administration of WT mice immediately before MI/R exerted detrimental effects on the reperfused heart. CRAMP exacerbates MI/R injury via a TLR4 and P2X7R/NLRP3 inflammasome-dependent mechanism, since I/R-induced myocardial infarction was reserved by inhibition of TLR4, P2X7R, or NLRP3 inflammasome in CRAMP-treated WT mice. Depletion of neutrophils before MI/R abrogated the amplification of infarct size in CRAMP-treated WT mice. Heart-infiltrating neutrophils were found to be one of major cellular sources of myocardial IL-1ß (a "first line" pro-inflammatory cytokine) at the early stage of MI/R. At this stage, CRAMP administration just before MI/R induced pro-IL-1ß protein expression in heart-infiltrating neutrophils, but not in non-neutrophils. In vitro experiments showed that LL-37 (the mature form of human cathelicidin) treatment promotes the processing and secretion of IL-1ß from human neutrophils via stimulating TLR4 signaling and P2X7R/NLRP3 inflammasome. CONCLUSIONS: Our findings reveal that, at the early stage of MI/R, neutrophil-derived cathelicidin plays an injurious role in the heart. Cathelicidin aggravates MI/R injury by over-activating TLR4 signaling and P2X7R/NLRP3 inflammasome in heart-infiltrating neutrophils, which leads to the excessive secretion of IL-1ß and subsequent inflammatory injury.

Electrochemical Immunoassay of Endothelin-1 Based on a Fenton-Type Reaction Using Cu(II)-Containing Nanocomposites as Nanozymes.

Endothelin-1 (ET-1) is a powerful endogenous vasoconstrictor and it is closely related to the pathogenesis of endothelial dysfunction that is commonly involved in the initiation of vascular inflammation and in the development of vascular diseases. A new method for the electrochemical immunoassay of ET-1 was put forward in this work. ET-1 antibodies (Ab), gold nanoparticles (GNPs), and copper ions were employed to synthesize nanoenzyme-labeled antibodies, Ab-GNPs-Cu(II) nanocomposites, and the latter was evaluated using transmission electron microscopy, dynamic light scattering, UV-vis absorption spectrophotometry, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. These nanocomposites could be captured on a glassy carbon electrode (GCE) modified with poly(thionine) (PTH) and ET-1, GCE/PTH/ET-1. The immobilized nanoenzymes, GNPs-Cu(II) nanoparticles, played a peroxidase mimic role. Hydroxyl radicals, •OH, generated by a Fenton-type reaction, oxidized PTH and induced the considerable cathodic current on an assembled sandwich-type electrode. Owing to the competitive immunoreaction, ET-1 in the solution inhibited the capture of Ab-GNPs-Cu(II) nanocomposites. The deficiency of •OH caused the decline of the electrochemical response. The cathodic current change was in proportion to the ET-1 concentration from 0.5 to 500 ng mL-1. Cell morphology and viability investigations show that human umbilical vein endothelial cells, HUVECs, suffered from dysfunction when they were incubated in the presence of high-concentration glucose. Analyses on the growth medium using the developed method reveal that ET-1 was secreted by the injured cells and the release level of ET-1 was associated positively with the glucose concentration in the growth medium.

A novel circular RNA, circ-ATAD1, contributes to gastric cancer cell progression by targeting miR-140-3p/YY1/PCIF1 signaling axis.

Circular RNAs (circRNAs) has been shown to be involved in the progression of various malignancies. Nevertheless, the mechanism of dysregulated circRNAs in gastric cancer (GC) remains to be understood. CircRNA microarray was utilized for identifying circRNA expression profiles in GC tissues. Circ-ATAD1 expression was measured by qRT-PCR. The clinical significance of circ-ATAD1 was analyzed by Fisher's exact test, Kaplan-Meier plots, and Cox regression model. The function of circ-ATAD1 was explored by using CCK-8, clone formation, flow cytometric and transwell experiments. RNA sequencing, bioinformatics, RNA pulldown, chromatin immunoprecipitation followed by sequencing, and dual-luciferase reporter assays were applied to determine the regulatory networks of circ-ATAD1 in GC cells. Circ-ATAD1 expression was increased in cancerous tissues. The prognostic value of circ-ATAD1 was identified in GC patients. For GC cells, circ-ATAD1 increased cell progression by sponging miR-140-3p to upregulate YY1. Additionally, YY1 directly bound to the promoter of PCIF1, thereby activating its transcription. Collectively, circ-ATAD1 plays an important role in GC tumorigenesis and progression and might be an important biomarker/therapeutic target for GC.

Cathelicidin deficiency exacerbates cardiac dysfunction in lipopolysaccharide-induced endotoxaemic mice.

The therapeutic potential of the antimicrobial peptide cathelicidin (Camp) administration in sepsis has been widely investigated. However, little is known about the pathophysiological roles of cathelicidin in septic cardiomyopathy. In a lipopolysaccharide (LPS)-induced endotoxaemic model, we found that the mRNA and protein expression of cardiac cathelicidin were induced in C57BL/6J wild-type (WT) mice upon LPS challenge, accompanied by increased circulating cathelicidin levels. We showed that this peptide was mainly derived from neutrophils and monocytes/macrophages. Camp deficiency exacerbated LPS-induced myocardial depression, while the administration of CRAMP (the mature form of mouse cathelicidin) decreased the LPS-induced mortality in a D-galactosamine hydrochloride (D-GalN)-sensitized endotoxin shock model. In vivo, LPS-treated Camp knockout mice had a significant higher protein level of myocardial and circulating tumour necrosis factor-alpha (TNF-α), a major contributing factor to septic cardiomyopathy, compared to LPS-treated WT mice, while CRAMP administration inhibited LPS-induced TNF-α production in the heart and plasma in D-GalN-sensitized endotoxaemic mice. In vitro, CRAMP treatment suppressed LPS-induced Tnf-α mRNA expression in cultured neonatal mouse cardiomyocytes and reduced TNF-α secretion in the culture supernatant. The inhibitory effects of CRAMP on TNF-α production may be related to its neutralizing ability of LPS, since CRAMP application had no effects on another toll-like receptor 4 ligand paclitaxel-induced Tnf-α mRNA expression in cardiomyocytes. These findings suggest that LPS-induced cathelicidin protects the heart against myocardial depression partly through the inhibition of TNF-α production via neutralizing LPS.

The items in the Chinese version of the Montreal cognitive assessment basic discriminate among different severities of Alzheimer's disease.

BACKGROUND: To determine whether items of the Chinese version of the Montreal Cognitive Assessment Basic (MoCA-BC) could discriminate among cognitively normal controls (NC), and those with mild cognitive impairment (MCI), mild Alzheimer's disease (AD), and moderate-severe (AD), as well as their sensitivity and specificity. METHODS: MCI (n = 456), mild AD (n = 502) and moderate-severe AD (n = 102) patients were recruited from the memory clinic, Huashan Hospital, Shanghai, China. NC (n = 329) were recruited from health checkup outpatients. Five MoCA-BC item scores were collected in interviews. RESULTS: The MoCA-BC orientation test had high sensitivity and specificity for discrimination among MCI, mild AD and moderate-severe AD. The delayed recall memory test had high sensitivity and specificity for MCI screening. The verbal fluency test was efficient for detecting MCI and differentiating AD severity. CONCLUSIONS: Various items of the MoCA-BC can identify MCI patients early and identify the severity of dementia.

Interhospital transfer on intravenous thrombolysis in patients with acute ischemic stroke in three chinese municipal stroke centers.

We included acute ischemic stroke (AIS) patients who received recombinant tissue plasminogen activator (rt-PA) at three stroke centers via either interhospital transfer or direct presentation and compared the clinical outcomes and time metrics to analyze the impact of interhospital transfer on intravenous thrombolysis (IVT). We retrospectively enrolled patients with AIS admitted to three stroke centers from October 1, 2016, to June 1, 2018. Patients treated with rt-PA were classified into the transfer and direct groups. We collected the patients' general information and time points. Statistical analyses were conducted to examine differences in the clinical outcomes and time metrics between the two groups. A total of 326 patients were enrolled, including 84 patients in the transfer group and 242 in the direct group. The transfer group had a longer onset-to-door time (OTD) (124.5 ± 50.6 min versus 83.2 ± 47.2 min, P < 0.01) but a shorter door-to-needle time (DNT) (53.0 ± 26.3 min versus 81.5 ± 31.1 min, P < 0.01), and the stroke onset-to-needle time was 177.4 ± 51.0 min versus 164.7 ± 53.3 min (P = 0.057). Compared with the direct group, the transfer group achieved similar modified Rankin scale (mRS) 0-2 outcomes (59.5% versus 58.7%, P = 0.768). Interhospital transfer was not an independent risk factor associated with a poor outcome at 90 days. In three Chinese municipal stroke centers, patients with an AIS referral have a longer OTD but a shorter DNT. DNTs of municipal hospitals were far longer than the current international standard, and their improvement is an important task.

The urate-lowering efficacy and safety of febuxostat versus allopurinol in Chinese patients with asymptomatic hyperuricemia and with chronic kidney disease stages 3-5.

BACKGROUND: While the dose of allopurinol is limited in patients with chronic kidney disease (CKD), information is lacking concerning the efficacy, safety, and maintenance dose of febuxostat in Chinese patients with hyperuricemia and with CKD stages 3-5. METHODS: A single center, prospective cohort study was conducted in patients with CKD stages 3-5 and with hyperuricemia who had not yet begun to undergo renal replacement therapy. We enrolled 208 patients who were newly treated with febuxostat (n = 112) or allopurinol (n = 96) in this study. The efficacy of febuxostat was determined by the proportion of patients with serum uric acid (sUA) < 360 µmol/L at the end of the study and changes of renal function. RESULTS: The target of sUA < 360 µmol/L was reached by 96.4% of participants in the febuxostat group and 37.5% in the allopurinol group at 6 months. The eGFR in the febuxostat group showed an increase from 28.45 to 30.65 mL/min/1.73 m2 at 6 months, while in the allopurinol group, the eGFR decreased from 28.06 to 24.39 mL/min/1.73 m2. Linear regression analysis showed that the reduction in sUA was significantly associated with an increase in eGFR and decrease in proteinuria. We found that 83.0% of the patients could remain with sUA < 360 µmol/L at a maintenance dose of febuxostat 20 mg/day. CONCLUSION: Febuxostat had superior urate-lowering efficacy to that of allopurinol in Chinese Han patients with hyperuricemia with CKD stages 3-5, and the reduction in sUA levels was associated with a slower progression of renal function.

Structural Change of a Single Ag Nanoparticle Observed by Dark-field Microspectroscopy.

Silver nanoparticles (AgNPs) have been widely used as photocatalysts and nanosensors. Observation of the spectroscopy of a single AgNP greatly helps us understand the catalytic characteristics and morphology change of the AgNP during reactions. In the present study, AgNPs physically adsorbed on indium tin oxide (ITO) conductive glass were electrochemically reduced and oxidized, and the plasmonic resonance Rayleigh scattering (PRRS) spectrum of an individual AgNP was observed under a dark-field microscopy (DFM) equipped with a spectrometer. The electrochemical oxidization of the AgNP under constant potential caused a redshift of the PRRS peak for 30±5 nm. However, electrochemical reduction of the AgNP could not make the PRRS peak completely shift back to the initial position. In situ AFM and SEM characterization confirmed that very small Ag fragments (<10 nm) formed around the AgNP core during electrochemical oxidization. Results showed that dark-field microspectroscopy could be used as a sensitive tool for estimating the morphology/structural changes of nanoparticles that can hardly be observed through the cyclic voltammograms of multiple AgNPs.

Effects of uric acid-lowering therapy on the progression of chronic kidney disease: a systematic review and meta-analysis.

OBJECTIVES: Whether uric acid levels were associated with the progression of chronic kidney disease (CKD) remained controversial. This meta-analysis was aimed to assess the effect of lowering serum uric acid therapy on the progression of CKD to clarify the role of uric acid in the progression of CKD indirectly. METHODS: Pubmed, Embase, the Cochrane library, CBM were searched for randomized controlled trials (RCTs) that assessed the efficiency of lowering serum uric acid therapy on the progression of CKD without language restriction. Summary estimates of weighted mean differences (WMDs) and relative risk (RR) were obtained by using random-effect or fixed-effect models. Sensitivity analyses were performed to identify the source of heterogeneity. RESULTS: A total of 12 randomized controlled trials with 832 CKD participants were included in the analysis. Pooled estimate for eGFR was in favor of lowering serum uric acid therapy with a mean difference (MD) of 3.88 ml/min/1.73 m2, 95% CI 1.26-6.49 ml/min/1.73 m2, p = .004 and this was consistent with results for serum creatinine. The risk of worsening of kidney function or ESRD or death was significantly decreased in the treatment group compared to the control group (RR 0.39, 95% CI 0.28-0.52, p< .01). CONCLUSIONS: Uric acid-lowering therapy may be effective in retarding the progression of CKD. Further randomized controlled trials should be performed to confirm the effect of lowering serum uric acid therapy on the progression of CKD.

Hot electron of Au nanorods activates the electrocatalysis of hydrogen evolution on MoS2 nanosheets.

Efficient water splitting through electrocatalysis holds great promise for producing hydrogen fuel in modern energy devices. Its real application however suffers from sluggish reaction kinetics due to the lack of high-performance catalysts except noble metals such as platinum. Herein, we report an active system of plasmonic-metal Au nanorods/molybdenum disulfide (MoS2) nanosheets hybrids for the hydrogen evolution reaction (HER). The plasmonic Au-MoS2 hybrids dramatically improve the HER, leading to a ∼3-fold increase of current under excitation of Au localized surface plasmon resonance (LSPR). A turnover of 8.76 s(-1) at 300 mV overpotential is measured under LSPR excitation, which by far exceeds the activity of MoS2 catalysts reported recently. The HER enhancement can be largely attributed to the increase of carrier density in MoS2 induced by the injection of hot electrons of Au nanorods. We demonstrate that the synergistic effect of the hole scavengers can further facilitate electron-hole separation, resulting in a decrease of the overpotential of HER at MoS2 to ∼120 mV. This study highlights how metal LSPR activates the HER and promises novel opportunities for enhancing intrinsic activities of semiconducting materials.

[Comparison of clinical application of exercise challenge test and methacholine challenge test in measurement of airway hyperresponsiveness].

OBJECTIVE: To compare the advantages and disadvantages between exercise challenge test (ECT) and methacholine challenge test (MCT) in the measurement of airway hyperresponsiveness (AHR), in order to identify a better and safer method to measure AHR. METHODS: Forty-seven children with controlled asthma after regular treatment were enrolled. ECT and MCT were performed for each child successively, and sensitivity was obtained through comparison with the golden standard (PD20). The occurrence of bronchospasm symptoms during the two tests was recorded. RESULTS: Taking PD20 as the gold standard, in children with moderate or severe AHR, the sensitivity of MCT (61%) for the measurement of AHR was significantly higher than that of ECT (9%) (P<0.05). The consistency between MCT results and PD20 was relatively high (κ=0.614), while the consistency between ECT results and PD20 was relatively low (κ=0.006). However, in the MCT, the incidence of bronchospasm symptoms was high and positively correlated with the incidence of cough and chest distress (P<0.05). CONCLUSIONS: MCT has a higher sensitivity for the measurement of AHR, but has a higher incidence of adverse events, compared with ECT in children with controlled asthma after regular treatment.