Altered spontaneous brain activities in maintenance hemodialysis patients with cognitive impairment and the construction of cognitive function prediction models.

OBJECTIVE: The brain neuromechanism in maintenance hemodialysis patients (MHD) with cognitive impairment (CI) remains unclear. The study aimed to probe the relationship between spontaneous brain activity and CI by using resting-state functional magnetic resonance imaging (rs-fMRI) data. METHODS: Here, 55 MHD patients with CI and 28 healthy controls were recruited. For baseline data, qualitative data were compared between groups using the χ2 test; quantitative data were compared between groups using the independent samples t-test, ANOVA test, Mann-Whitney U-test, or Kruskal-Wallis test. Comparisons of ALFF/fALFF/ReHo values among the three groups were calculated by using the DPABI toolbox, and then analyzing the correlation with clinical variables. p < .05 was considered a statistically significant difference. Furthermore, back propagation neural network (BPNN) was utilized to predict cognitive function. RESULTS: Compared with the MHD-NCI group, the patients with MHD-CI had more severe anemia and higher urea nitrogen levels, lower mALFF values in the left postcentral gyrus, lower mfALFF values in the left inferior temporal gyrus, and greater mALFF values in the right caudate nucleus (p < .05). The above-altered indicators were correlated with MOCA scores. BPNN prediction models indicated that the diagnostic efficacy of the model which inputs were hemoglobin, urea nitrogen, and mALFF value in the left central posterior gyrus was optimal (R2 = 0.8054), validation cohort (R2 = 0.7328). CONCLUSION: The rs-fMRI can reveal the neurophysiological mechanism of cognitive impairment in MHD patients. In addition, it can serve as a neuroimaging marker for diagnosing and evaluating cognitive impairment in MHD patients.

Physiologically based pharmacokinetic combined BTK occupancy modeling for optimal dosing regimen prediction of acalabrutinib in patients alone, with different CYP3A4 variants, co-administered with CYP3A4 modulators and with hepatic impairment.

PURPOSE: To develop a mathematical model combined between physiologically based pharmacokinetic and BTK occupancy (PBPK-BO) to simultaneously predict pharmacokinetic (PK) and pharmacodynamic (PD) changes of acalabrutinib (ACA) and active metabolite ACP-5862 in healthy humans as well as PD in patients. Next, to use the PBPK-BO to determine the optimal dosing regimens in patients alone, with different CYP3A4 variants, when co-administration with four CYP3A4 modulators and in patients with hepatic impairment, respectively. METHODS: The PBPK-BO model was built using physicochemical and biochemical properties of ACA and ACP-5862 and then verified by observed PK and PD data from healthy humans and patients. Finally, the model was applied to determine optimal dosing regimens in various clinical situations. RESULTS: The simulations demonstrated that 100 mg ACA twice daily (BID) was the optimal dosing regimen in patients alone. Additionally, dosage regimens might be reduced to 50 mg BID in patients with five CYP3A4 variants. Moreover, the dosing regimen should be modified to 100 mg (even to 50 mg) once daily (QD) when co-administration with erythromycin or clarithromycin, and be increased to 200 mg BID with rifampicin, and but be avoided co-administration with itraconazole. Furthermore, dosage regimen simulations showed that optimal dosing might be decreased to 50 mg BID in patients with mild and moderate hepatic impairment, and be avoided taking ACA in severely hepatically impaired patients. CONCLUSION: This PBPK-BO model can predict PK and PD in healthy humans and patients and also predict the optimal dosing regimens in various clinical situations.

Structural, magnetic, and electronic properties of EuSi2 thin films on the Si(111) surface.

Searching for magnetic silicide thin films has long been a hot topic in condensed matter physics and materials science based on their fundamental physics and promising device applications. Here we report a systematic study on the structural, magnetic, and electronic properties of EuSi2 thin films on the Si(111) surface by ab initio calculations. Total energy calculations show that the EuSi2 thin film in AA stacking is more favorable than that in AB or ABC stacking. The Eu2 + ions are coupled ferromagnetically within each layer and antiferromagnetically across the adjacent silicene layers with a large local spin moment of 6.96-7.00µB derived from the Eu-4f orbital electrons. Electronic band structure calculations indicate that the monolayer EuSi2 thin film is a semiconductor with an indirect surface band gap of 0.45 eV, while the multilayer EuSi2 thin films exhibit metallic behavior. These findings provide a systematic understanding of rare-earth metal silicides on the Si surface and will provide guidance for Si-based nanoelectronics and spintronics.

La induced Si3 trimer bilayer on the Si(111) surface.

Using first-principles calculations, we identify a robust R30° reconstruction of a Si3 trimer bilayer on the Si(111) surface with a La coverage of 2/3 monolayer. Each surface unit cell contains two Si3 trimers and two La atoms, where the upper Si3 trimer is located just above the lower one with a rotation of about 60°, while two La atoms with different heights are distributed between the Si3 trimers and located on the T4 top site of the Si(111) surface, forming a honeycomb-like network structure. We find that the two La atoms have different valence states, La2+ and La3+, respectively. The high structural stability is attributed to the lower La atom saturating all the three dangling bonds of the upper Si3 trimer, while the higher La atom compensates two electrons to the lower Si3 trimer. The electronic band structure and band-decomposed charge density distribution show a semiconducting characteristic with a small surface band gap of 42 meV. Moreover, simulated STM images show a good structural match with the recent experimental observations.

Structural stability and electronic properties of alkaline-earth metal induced Si(111)-(3 × 2) surfaces.

Alkaline-earth metal (Ca, Sr, and Ba) induced Si(111)-(3 × 2) honeycomb chain-channel (HCC) surfaces have been systematically studied by means of ab initio calculations. The large adsorption energy and anisotropic diffusion energy barriers ensure the high structural stability of the one-dimensional HCC structure. Electronic band structures and band-decomposed charge density distributions reveal that the first conduction band and the third valence band level are contributed by the surface Si and metal atoms, while the top first and second valence bands are caused by the bulk silicon atoms. These results identify a larger surface band gap of 1.65-1.68 eV and provide an excellent explanation for the recent experimental observations of a band gap of 1.7 eV for the Sr/Si(111)-(3 × 2) HCC surface.

DL-Propargylglycine protects against myocardial injury induced by chronic intermittent hypoxia through inhibition of endoplasmic reticulum stress.

BACKGROUND: Chronic intermittent hypoxia (CIH), an important basis of the pathogenesis of organ damage induced by obstructive sleep apnea syndrome (OSAS), is associated with myocardial injury, such as left ventricular dysfunction, apoptosis, and oxidative stress. Endogenous hydrogen sulfide (H2S) plays an important role in maintaining cardiovascular functions. Many studies have demonstrated that exogenous H2S has protective effects against myocardial injury induced by various cardiovascular diseases, and inhibiting the generation of endogenous H2S has opposite effects. However, the effect of DL-propargylglycine (PAG), an effective inhibitor of cystathionine γ-lyase (CSE)-synthesized H2S, on the regulation myocardial injury remains controversial. PURPOSE: The present study was aimed to explore the influence of PAG on myocardial injury induced in rats by CIH. METHODS: Sprague-Dawley rats were randomly divided into a normal control (NC) group, a CIH group, a NC + PAG group, and a CIH + PAG group. After establishing the CIH model in rats, blood pressure, left ventricular function, oxidative stress, apoptosis, and the level of endoplasmic reticulum (ER) stress were detected. RESULTS: In NC rats, PAG had no effect on blood pressure, but induced myocardial dysfunction and up-regulated oxidative stress and apoptosis of the myocardium. In the CIH + PAG group, pretreatment with PAG significantly reduced blood pressure and improved the left ventricular ejection fraction (LVEF) and the left ventricular fractional shortening (LVFS) compared to the CIH group. Significantly lower levels of oxidative stress, apoptosis, and the ER stress were detected in the CIH + PAG group than in the CIH group. CONCLUSION: These results suggest that PAG can protect the myocardium against CIH-induced injury through inhibition of endoplasmic reticulum stress.

The role of the Nox4-derived ROS-mediated RhoA/Rho kinase pathway in rat hypertension induced by chronic intermittent hypoxia.

BACKGROUND: Obstructive sleep apnea syndrome, which is a risk factor for resistant hypertension, is characterized by chronic intermittent hypoxia (CIH) and is associated with many cardiovascular diseases. CIH elicits systemic oxidative stress and sympathetic hyperactivity, which lead to hypertension. Rho kinases (ROCKs) are considered to be major effectors of the small GTPase RhoA and have been extensively studied in the cardiovascular field. Upregulation of the RhoA/ROCK signaling cascade is observed in various cardiovascular disorders, such as atherosclerosis, pulmonary hypertension, and stroke. However, the exact molecular function of RhoA/ROCK in CIH remains unclear and requires further study. OBJECTIVE: This study aimed to investigate the role of the NADPH oxidase 4 (Nox4)-induced ROS/RhoA/ROCK pathway in CIH-induced hypertension in rats. METHODS: Male Sprague-Dawley rats were exposed to CIH for 21 days (intermittent hypoxia of 21% O2 for 60 s and 5% O2 for 30 s, cyclically repeated for 8 h/day). We randomly assigned 56 male rats to groups of normoxia (RA) or vertically implemented CIH together with vehicle (CIH-V), GKT137831 (CIH-G), N-acetyl cysteine (NAC) (CIH-N), or Y27632 (CIH-Y). The rats in the RA group were continuously exposed to room air, whereas the rats in the other groups were exposed to CIH. Systolic blood pressure (BP) was monitored at the beginning of each week. After the experiment, renal sympathetic nerve activity (RSNA) was recorded, and serum and renal tissues were subjected to molecular biological and biochemical analyses. RESULTS: Compared with the BP of RA rats, the BP of CIH-V rats started to increase 2 weeks after the beginning of the experiment, subsequently stabilizing at a high level at the end of the third week. CIH increased both RSNA and oxidative stress. This response was attenuated by treatment of the rats with GKT137831 or NAC. Inhibiting Nox4 activity or ROS production reduced RhoA/ROCK expression. Treatment with Y27632 reduced both BP and RSNA in rats exposed to CIH. CONCLUSION: Hypertension can be induced by CIH in SD rats. The CIH-induced elevation of BP is at least partially mediated via the Nox4-induced ROS/RhoA/ROCK pathway.

Conformational Insights into the Mechanism of Acetylaminofluorene-dG-Induced Frameshift Mutations in the NarI Mutational Hotspot.

Frameshift mutagenesis encompasses the gain or loss of DNA base pairs, resulting in altered genetic outcomes. The NarI restriction site sequence 5'-G1G2CG3CX-3' in Escherichia coli is a well-known mutational hotspot, in which lesioning of acetylaminofluorene (AAF) at G3* induces a greater -2 deletion frequency than that at other guanine sites. Its mutational efficiency is modulated by the nature of the nucleotide in the X position (C ∼ A > G ≫ T). Here, we conducted a series of polymerase-free solution experiments that examine the conformational and thermodynamic basis underlying the propensity of adducted G3 to form a slipped mutagenic intermediate (SMI) and its sequence dependence during translesion synthesis (TLS). Instability of the AAF-dG3:dC pair at the replication fork promoted slippage to form a G*C bulge-out SMI structure, consisting of S- ("lesion stacked") and B-SMI ("lesion exposed") conformations, with conformational rigidity increasing as a function of primer elongation. We found greater stability of the S- compared to the B-SMI conformer throughout TLS. The dependence of their population ratios was determined by the 3'-next flanking base X at fully elongated bulge structures, with 59% B/41% S and 86% B/14% S for the dC and dT series, respectively. These results indicate the importance of direct interactions of the hydrophobic AAF lesion with the 3'-next flanking base pair and its stacking fit within the -2 bulge structure. A detailed conformational understanding of the SMI structures and their sequence dependence may provide a useful model for DNA polymerase complexes.

Downregulation of MLL3 in esophageal squamous cell carcinoma is required for the growth and metastasis of cancer cells.

The mixed lineage leukemia 3 (MLL3), a member of the mixed lineage leukemia (MLL) family, has been reported to be mutated in multiple cancer types. However, its function in esophageal squamous cell carcinoma (ESCC) remains poorly understood. Here, we found that the expression of MLL3 was downregulated in ESCC tissues. Moreover, over-expression of MLL3 in ESCC cells inhibited cell proliferation and migration, while the knockdown expression of MLL3 promoted the tumorigenicity of ESCC cells. Mechanistically, MLL3 regulated the expression of multiple growth-related and migration-related genes. Taken together, our study suggested that downregulation of MLL3 was very important in the progression of ESCC.

Identification of susceptibility genes in non-syndromic cleft lip with or without cleft palate using whole-exome sequencing.

BACKGROUND: Non-syndromic cleft lip with or without cleft palate (NSCL/P) is among the most common congenital malformations. The etiology of NSCL/P remains poorly characterized owing to its complex genetic heterogeneity. The objective of this study was to identify genetic variants that increase susceptibility to NSCL/P. MATERIAL AND METHODS: Whole-exome sequencing (WES) was performed in 8 fetuses with NSCL/P in China. Bioinformatics analysis was performed using commercially available software. Variants detected by WES were validated by Sanger sequencing. RESULTS: By filtering out synonymous variants in exons, we identified average 8575 nonsynonymous single nucleotide variants (SNVs). We subsequently compared the SNVs against public databases including NCBI dbSNP build 135 and 1000 Genomes Project and obtained an average of 203 SNVs. Total 12 reported candidate genes were verified by Sanger sequencing. Sanger sequencing also confirmed 16 novel SNVs shared by two or more samples. CONCLUSIONS: We have found and confirmed 16 susceptibility genes responsible for NSCL/P, which may play important role in the etiology of NSCL/P. The susceptibility genes identified in this study will not only be useful in revealing the etiology of NSCL/P but also in diagnosis and treatment of the patients with NSCL/P.

Real-time surface plasmon resonance study of biomolecular interactions between polymerase and bulky mutagenic DNA lesions.

Surface plasmon resonance (SPR) was used to measure polymerase-binding interactions of the bulky mutagenic DNA lesions N-(2'-deoxyguanosin-8-yl)-4'-fluoro-4-aminobiphenyl (FABP) or N-(2'-deoxyguanosin-8-yl)-7-fluoro-2-acetylaminofluorene (FAAF) in the context of two unique 5'-flanking bases (CG*A and TG*A). The enzymes used were exo-nuclease-deficient Klenow fragment (Kf-exo(-)) or polymerase ß (pol ß). Specific binary and ternary DNA binding affinities of the enzymes were characterized at subnanomolar concentrations. The SPR results showed that Kf-exo(-) binds strongly to a double strand/single strand template/primer junction, whereas pol ß binds preferentially to double-stranded DNA having a one-nucleotide gap. Both enzymes exhibited tight binding to native DNA, with high nucleotide selectivity, where the KD values for each base pair increased in the order dCTP ≪ dTTP ∼ dATP ≪ dGTP. In contrast to that for pol ß, Kf-exo(-) binds tightly to lesion-modified templates; however, both polymerases exhibited minimal nucleotide selectivity toward adducted DNA. Primer steady-state kinetics and (19)F NMR results support the SPR data. The relative insertion efficiency fins of dCTP opposite FABP was significantly higher in the TG*A sequence compared to that in CG*A. Although Kf-exo(-) was not sensitive to the presence of a DNA lesion, FAAF-induced conformational heterogeneity perturbed the active site of pol ß, weakening the enzyme's ability to bind to FAAF adducts compared to FABP adducts. The present study demonstrates the effectiveness of SPR for elucidating how lesion-induced conformational heterogeneity affects the binding capability of polymerases and ultimately the nucleotide insertion efficiency.

Constrained multiobjective biogeography optimization algorithm.

Multiobjective optimization involves minimizing or maximizing multiple objective functions subject to a set of constraints. In this study, a novel constrained multiobjective biogeography optimization algorithm (CMBOA) is proposed. It is the first biogeography optimization algorithm for constrained multiobjective optimization. In CMBOA, a disturbance migration operator is designed to generate diverse feasible individuals in order to promote the diversity of individuals on Pareto front. Infeasible individuals nearby feasible region are evolved to feasibility by recombining with their nearest nondominated feasible individuals. The convergence of CMBOA is proved by using probability theory. The performance of CMBOA is evaluated on a set of 6 benchmark problems and experimental results show that the CMBOA performs better than or similar to the classical NSGA-II and IS-MOEA.

Binary and ternary binding affinities between exonuclease-deficient Klenow fragment (Kf-exo(-)) and various arylamine DNA lesions characterized by surface plasmon resonance.

We used surface plasmon resonance (SPR) to characterize the binding interactions between the exonulease-free Klenow fragment (Kf-exo(-)) and unmodified and modified dG adducts derived from arylamine carcinogens: fluorinated 2-aminofluorene (FAF), 2-acetylaminofluorene (FAAF), and 4-aminobiphenyl (FABP). Tight polymerase binding was detected with unmodified dG and the correct dCTP. The discrimination of correct versus incorrect nucleotides was pronounced with K(D) values in the order of dCTP ≪ dTTP < dATP < dGTP. In contrast, minimal selectivity was observed for the modified templates with Kf-exo(-) binding tighter to the FAAF (k(off): 0.02 s(-1)) and FABP (k(off): 0.01 s(-1)) lesions than to FAF (k(off): 0.04 s(-1)).

Identification of a miRNA biomarker for the large artery atherosclerosis subtype of acute ischemic stroke.

AIM OF THE STUDY: To identify miRNA biomarkers of arterial atherosclerosis subtypes in acute ischemic stroke. MATERIAL AND METHODS: 40 participants recruited in our hospital from October 2017 to January 2018. There were 12 patients with acute ischemic stroke (AIS), 13 patients with atherosclerosis (AS) and 15 healthy subjects. They were divided into the AIS group, AS group and healthy control (HC) group. The miRNA expression levels of the AIS group, AS group and HC group were measured by DNA microarray. Bioinformatics analysis was performed using the miRNA target prediction database. RESULTS: The expression of 3 miRNAs, miR-129-1-3p, miR-4312, miR-5196-3p, was significantly different between the AIS and AS/HC groups. Genes targeted by miR-129-1-3p were involved in 12 pathways, of which axon guidance, retrograde endocannabinoid signalling and sphingolipid signalling pathways were associated with axonal and synaptic function. miR-129-1-3p mimics significantly decreased cortical neurite length and Runx2 levels, while miR-129-1-3p inhibitors promoted neurite growth and increased Runx2 expression. CONCLUSIONS: miR-129-1-3p may be a relevant biomarker for the diagnosis of stroke caused by large artery atherosclerosis and could represent a novel therapeutic target for stroke treatment.

Analytical comparability demonstrated for an IgG4 molecule, inclacumab, following transfer of manufacturing responsibility from Roche to Global Blood Therapeutics.

BACKGROUND: Inclacumab is a recombinant, fully human, immunoglobulin IgG4 monoclonal antibody that selectively binds to P-selectin. Initially discovered and developed by Roche through phase 2 clinical studies in peripheral arterial disease and coronary artery disease, inclacumab has been in-licensed by Global Blood Therapeutics (GBT) as a potential treatment to reduce the frequency of vaso-occlusive crises in individuals with sickle cell disease. RESEARCH DESIGN AND METHODS: GBT sought to demonstrate the analytical comparability between material produced by Roche and material produced by GBT to ensure that no meaningful differences in identity, safety, purity, potency, or bioavailability exist between the GBT and Roche lots. RESULTS: Inclacumab samples produced by GBT were found to be comparable to the Roche v0.2 inclacumab samples based on (1) comparable primary and higher-order structures; (2) comparable purity profiles; (3) comparable potency, in vitro functional activities, and in vivo plasma exposures and pharmacokinetic profiles; and (4) comparable degradation patterns and kinetics under forced degradation conditions. CONCLUSIONS: Based on the design of this comparability study and the results obtained, the US Food and Drug Administration approved the changes to the manufacturing process and gave clearance for GBT to proceed with phase 3 clinical trials.

Mn-Doped Sr/Si(111)-(3 × 2) HCC Surfaces: Antiferromagnetic Semiconductors for Spintronic Applications.

Manganese and manganese silicide as promising candidates for spintronic applications have attracted great interest in recent years. Here, we adopt Sr-induced Si(111)-(3 × 2) honeycomb-chain channel (HCC) surface as a template and perform a systematical study on the structural stability and magnetic and electronic properties of Mn-doped Sr/Si(111)-(3 × 2) HCC surfaces by ab initio calculations. Our energetic and kinetic results show two robust inserting structures M6 and H4, where Mn atoms are located below the honeycomb Si chain and on the top or hollow site of the Si(111) surface. Their high structural stabilities are attributed to the doped Mn atoms that saturate all the dangling bonds of Si(111) surface. In these two structures, Mn atoms prefer antiferromagnetic coupling with the same local magnetic moment of 3 µB. Electronic band structures and band-decomposed charge density distributions reveal that these two stable surface structures have a semiconducting characteristic with a surface band gap of 0.21-0.28 eV. This work provides an antiferromagnetic system for the possible application in spintronics.

Prognostic Role of Serum Lactate Dehydrogenase in Patients With Urothelial Carcinoma: A Systematic Review and Meta-Analysis.

Background: To investigate the potential prognostic role of serum lactate dehydrogenase (LDH) in patients with urothelial carcinoma (UC) using the method of systematic review and meta-analysis. Materials and Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science for eligible studies up to February 2020. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were used to estimate the relationship. Results: A total of 14 studies including 4,009 patients with UC were incorporated. The results showed that a high pretreatment serum LDH was associated with an inferior overall survival (OS, HR 1.61, 95% CI 1.39-1.87, p < 0.001), cancer-specific survival (CSS, HR 1.41, 95% CI 1.05-1.90, p = 0.022), and disease-free survival (DFS, HR 1.64, 95% CI 1.04-2.59, p = 0.034) in UC. Subgroup analyses identified that a high pretreatment serum LDH was associated with a poor OS (HR 1.97, 95% CI 1.02-3.81, p = 0.042) and DFS (HR 1.64, 95% CI 1.04-2.59, p = 0.034) in upper tract urothelial carcinoma, a short OS (HR 1.71, 95% CI 1.37-2.15, p < 0.001) in urothelial carcinoma of bladder. Conclusion: Our findings indicated that a high level of pretreatment serum LDH was associated with inferior OS, CSS, and DFS in patients with UC. This biomarker can be an important factor incorporated into the prognostic models for UC.

Effects of age on the peak ratio of ophthalmic artery Doppler.

ABSTRACT: This study aimed to investigate the effects of age on the peak ratio (PR) of ophthalmic artery (OA) Doppler.The initial peak velocity (P1), second peak velocity (P2) and PR of OA were detected by color Doppler ultrasonography in 147 healthy subjects. All of the subjects were divided into 6 groups (G1-G6) according to the age. (G1, 20-29 years; G2, 30-39 years; G3, 40-49 years; G4, 50-59 years; G5, 60-69 years; and G6, 70 years or older). The blood pressure and heart rate were also examined before ultrasonography. The influences of age, blood pressure and heart rate on the P1, P2, and PR were further evaluated.There were significant differences in the P2 and PR among different age groups except for P1. There were no significant differences in the P2 and PR between the first 2 groups, neither among the latter 4 groups. Nevertheless, P2 and PR in the first 2 groups were significantly different from those in the latter 4 groups. In addition, both P2 and PR (not P1) increased significantly with age, systolic and diastolic blood pressure. P1, P2 and PR were not related to heart rate. Both P2 and PR were closely related to the age. PR also had a weak relationship with systolic blood pressure.Both P2 and PR of OA Doppler increase with age. Concern should be raised when P2 and PR are used to evaluate the hemodynamic change of OA.

[Study on fingerprints of Citrus aurantium from different places by capillary electrophoresis].

OBJECTIVE: To develop a high performance capillary electrophoresis method for Citrus aurantium fingerprints to control its quality. METHOD: The background electrolyte (BGE) was an 80 mmol x L(-1) boric acid solution containing 15 mmol x L(-1) borate. The pH of the BGE was adjusted to 9.70 with KOH solution. The detection wavelength was 201 nm and a voltage of 16 kV was applied. The sample hydrodynamic injection was 0.4 ps with a duration time of 8 sec. C. aurantium was extracted by water and a set of capillary electrophoresis fingerprints (CEFP) containing 12 co-possessing peaks was obtained. RESULT: There were good similarities between the standard CEFP and each set of CEFP of C. aurantium collected from eleven different places, and their similarity coefficients were between 0.973 and 0.996. CONCLUSION: The CEFP has acceptable precision, reproducibility and stability and can be used for the quality control of C. aurantium.

Adenotonsillectomy can decrease enuresis and sympathetic nervous activity in children with obstructive sleep apnea syndrome.

BACKGROUND: The nocturnal intermittent hypoxia caused by obstructive sleep apnea syndrome (OSAS) can provoke the sympathetic nervous activity (SNA). Salivary alpha-amylase (sAA) is a sensitive, non-invasive biomarker for reflecting the SNA, and a useful marker for pediatric OSAS subjects. Adenotonsillar hypertrophy (ATH) is the most commonly identified risk factor in OSAS childhood, therefore, several studies showed that the adenotonsillectomy (T&A) may alleviate nocturnal enuresis (NE) in children with OSAS. OBJECTIVE: The present study was to investigate the effect of T&A on NE, the change of sAA value in ATH and OSAS children, with/without NE, and with/without the operation. STUDY DESIGN: 37 children (Group A) were admitted for ATH and NE. The saliva samples were taken before and after polysomnography for the measure of sAA. After the T&A, the children were followed-up for 1 year. 35 OSAS children with NE but no T&A were as a NE watchful-waiting group (Group B), 32 subjects without OSAS or NE were as non-OSAS control (Group C), 42 cases who underwent T&A but did not have NE were admitted to evaluate the SNA (Group D). Follow-up included evaluations for NE, sAA and urinary catecholamine after the T&A or at the equivalent time points. RESULTS: The observational results in the present study showed a significant rate of the disappearance of NE 1 month after the T&A and had an almost complete resolution 1 year later. OSAS may irritate oxidative stress and increase SNA in pediatric subjects, which reflected by increased levels of sAA and urinary catecholamine, while the T&A can decrease enuresis and the SNA in children with OSAS (Figure). DISCUSSION: Little research has previously focused on the relationship between childhood OSAS and the SNA. No data are currently available regarding comparisons of sAA levels before and after the T&A in children with OSAS and enuresis. Our findings in this present study showed that there was a resolution or decrease in enuresis events and drops in sAA levels following T&A, which were consistent with earlier study. However, there was no significant difference in the urinary catecholamine levels was found between OSAS groups with or without NE. Furthermore, there was no correlation between the urinary catecholamine and polysomnography parameters. CONCLUSIONS: T&A has a favorable therapeutic effect on NE and may decrease SNA in children with OSAS. sAA might be associated with instability of ANS by OSAS and have a consistent relationship with the apnea-hypopnea index. Our studying aims had been met.