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Background: Exosomes are involved in cell-to-cell communication in numerous diseases including cardiovascular diseases, neurological diseases. Little attention has been dedicated to exosomal circular RNAs in obstructive sleep apnea (OSA)-related cardiovascular diseases. The aim of this study was to explore the role of exosomal circular RNA ZNF292 (circZNF292) on AC16 cells exposure to intermittent hypoxia (IH)., Methods: Exosome release inhibitor GW4869 was used to examine the effect of exosomes on IH-induced AC16 cells apoptosis. The expression of exosomal circZNF292 was detected by qRT-PCR in AC16 cells exposure to IH, and a luciferase reporter assay was conducted to confirm the connection between circZNF292 and miR-146a-5p. Exosomal circZNF292 was stably transfected with short hairpin RNAs (shRNAs) against circZNF292 and co-cultured with AC16 cells. The expression of miR-146a-5p and apoptosis-related protein was then measured to evaluate the effect of exosomal circZNF292., Results: We found that IH contributed to the AC16 cells apoptosis, and the administration of GW4869 increased the apoptosis of cardiomyocytes when exposed to IH. The expression of exosomal circZNF292 decreased and miR-146a-5p increased significantly in AC16 cells exposed to IH compared to normoxic conditions. Bioinformatics analysis predicted a circZNF292/miR-146a-5p axis in IH-induced cardiomyocytes apoptosis. The dual-luciferase reporter system validated the direct interaction of circZNF292 and miR-146a-5p. Knockdown of circZNF292 increased the expressions of miR-146a-5p and accelerated the AC16 cardiomyocytes apoptosis., Conclusions: The findings of this study suggested a novel mechanism by which exosomes transmit intrinsic regulatory signals to the myocardium through the exosomal circZNF292/miR-146a-5p axis. This finding highlights the potential of targeting this pathway as a therapeutic approach for treating cardiovascular diseases associated with OSA., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

An efficient protocol for photocatalytic degradation of organic dyes and antibiotics has been successfully established via MOF-derived (MOF = metal-organic framework) Ni, Co-embedded N-doped bimetallic porous carbon nanocomposites (NiCo/NC). Such a NiCo/NC nanocomposite features well-distributed structures, suitable specific surface areas, and more active sites determined by various characterization analyses. The catalyst exhibits higher photocatalytic performance and stability toward the liquid-phase degradation of methylene blue (MB) under visible light irradiation for 60 min, after the adsorption-desorption equilibrium and the thorough degradation into H 2 O and CO 2 . Radical quenching experiments further confirmed the dominant effect of electron holes h + and superoxide radical anions ·O 2 - for the MB photodegradation process. NiCo/NC was also appropriate for the degradation of Rhodamine B, methyl orange, tetracycline hydrochloride, and norfloxacin. Moreover, NiCo/NC is robust, and its photocatalytic activity is basically maintained after 8 cycles. This work is expected to provide additional information for the design of MOF-derived carbon material with more excellent properties and lay the foundation for further industrial applications., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: The conventional midline approach for lumbar puncture (MAT-LP) has a relatively low success rate of 70%. The paramedian approach can increase the effective puncture area and success rate but lacks standardized guidelines. This study evaluated a computer-modified paramedian approach technique (CMPAT) to optimize lumbar puncture using computational techniques., Methods: In this prospective study, 120 patients underwent CMPAT-LP ( n  = 60) or MAT-LP ( n  = 60). Puncture failure was defined after 6 attempts. Failure rate, number of attempts, pain score, and complications were compared. Subgroup analysis was conducted for age (≥ 50 years)., Results: No significant demographic differences existed between groups. Failure rates were 3.3% for CMPAT vs. 13.3% for MAT. Puncture attempts averaged 2.0 vs. 3.5 and pain scores were 2.7 vs. 4.1 for CMPAT and MAT, respectively. All outcomes were significantly improved with CMPAT, especially in elderly patients. No significant difference in complications was observed., Conclusion: Compared to MAT, CMPAT-LP demonstrated lower failure rates, fewer puncture attempts, and less pain, without compromising safety. CMPAT may be superior and should be more widely implemented in clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhuang, Xie, Chen, Wu, Wu and Chen.)

Objectives: The aim of this study was to evaluate the performance of consolidation-to-tumour ratio (CTR) and the radiomic models in two- and three-dimensional modalities for assessing radiological invasiveness in early-stage lung adenocarcinoma., Methods: A retrospective analysis was conducted on patients with early-stage lung adenocarcinoma from Guangdong Provincial People's Hospital and Shenzhen People's Hospital. Manual delineation of pulmonary nodules along the boundary was performed on cross-sectional images to extract radiomic features. Clinicopathological characteristics and radiomic signatures were identified in both cohorts. CTR and radiomic score for every patient were calculated. The performance of CTR and radiomic models were tested and validated in the respective cohorts., Results: A total of 818 patients from Guangdong Provincial People's Hospital were included in the primary cohort, while 474 patients from Shenzhen People's Hospital constituted an independent validation cohort. Both CTR and radiomic score were identified as independent factors for predicting pathological invasiveness. CTR in two- and three-dimensional modalities exhibited comparable results with areas under the receiver operating characteristic curves and were demonstrated in the validation cohort (area under the curve: 0.807 vs 0.826, P = 0.059) Furthermore, both CTR in two- and three-dimensional modalities was able to stratify patients with significant relapse-free survival (P < 0.000 vs P < 0.000) and overall survival (P = 0.003 vs P = 0.001). The radiomic models in two- and three-dimensional modalities demonstrated favourable discrimination and calibration in independent cohorts (P = 0.189)., Conclusions: Three-dimensional measurement provides no additional clinical benefit compared to two-dimensional., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Purpose: Circular RNAs (circRNAs) are recently identified as a class of non-coding RNAs that participate in the incidence of acute myocardial infarction (AMI). However, circRNAs expression pattern in obstructive sleep apnea (OSA) with AMI remains unknown. The aim was to investigate circRNAs expression alteration in serum exosomes derived from OSA patients with AMI., Methods: The serum exosomal circRNAs profile of three healthy subjects, three OSA without AMI and three OSA with AMI were analyzed using high-throughput sequencing. Bioinformatic analyses were carried out to assess potential core circRNAs and functional analyses were conducted to study biological functions., Results: Compared to healthy subjects, there were 5225 upregulated and 5798 downregulated circRNAs in exosomes from OSA with AMI patients. And our study also identified 5210 upregulated and 5813 downregulated circRNAs in OSA with AMI patients compared to OSA without AMI. The differential expression of 2 circRNAs (hsa&#95;circRNA&#95;101147, hsa&#95;circRNA&#95;101561) between healthy subjects and OSA without AMI, and 4 circRNAs (hsa&#95;circRNA&#95;101328, hsa&#95;circRNA&#95;104172, hsa&#95;circRNA&#95;104640, hsa&#95;circRNA&#95;104642) between healthy subjects and OSA with AMI were confirmed by qRT-PCR. In addition, we demonstrated that miR-29a-3p targeted hsa&#95;circRNA&#95;104642 directly., Conclusions: This study demonstrated that there were a number of dysregulated circRNAs in exosomes from OSA with AMI patients, which might be effectively served as a promising diagnostic biomarker and therapeutic targets., (© 2023. The Author(s).)

Stable and efficient photocatalytic degradation of organic pollutants has been achieved via a ZIF-67-derived Co-embedded N-doped nanoporous carbon material catalyst (Co-N/C). The catalyst features a well-distributed structure, suitable specific surface area, and more active sites according to the various characterization analyses. The photocatalytic activity of Co-N/C was evaluated by the degradation of the target pollutant Rhodamine B (RhB). As a result, RhB could establish an adsorption-desorption equilibrium in the dark within 30 min and was thoroughly degraded into H 2 O and CO 2 by Co-N/C under 500 W visible light irradiation in 40 min. Moreover, radical-quenching experiments and reactive oxygen species monitoring were performed to further probe the plausible photodegradation mechanism of RhB. Co-N/C is also appropriate for other alternative dyes and antibiotics affording ideal removal efficiencies. After the reaction, Co-N/C could be facilely separated by an external magnetic field and reused for eight reaction cycles without obvious deactivation of its photocatalytic properties. This study is expected to provide an instructive guideline for the design of efficient and recyclable composite photocatalysts derived from metal-organic frameworks for a broad range of environmental remediation processes., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Background: Hypoxia in obstructive sleep apnea (OSA) patients during sleep may have an effect on bone metabolism. Few data regarding evaluation of bone metabolism in young individuals diagnosed with OSA. In this study, we aim to identify the association between bone mineral density and OSA in young men (≤ 40 years old of age)., Methods: Consecutive male subjects who underwent polysomnography were enrolled. Serum calcium, 25-hydroxyvitamin-D3, β-isomerized form C-terminal telopeptide of type I collagen, osteocalcin and procollagen type 1 N-propeptide were measured in all participants, and bone mineral density (BMD) at lumbar spine (L1-L4), femoral neck and hip total were determined by dual energy X-ray absorption (DXA)., Results: The population consisted of 85 subjects (mean age 35.53 years). The BMD at lumbar spine (L1-L4) in moderate OSA patients was higher than control and severe OSA group significantly (p = 0.036). After adjustment for confounding factors, stepwise multiple linear regression analyses showed LaSO 2 (β = 0.340, p = 0.008) as an independent explanatory variable for Lumbar L1-L4 BMD, LaSO 2 (β = 0.304, p = 0.037), BMI (β = 0.393, p = 0.008) for femur neck BMD and BMI (β = 0.720, p = 0.002) for hip total BMD., Conclusions: Our finding indicated that there was a relationship between OSA and bone metabolism in younger men, and moderate OSA-related hypoxia positively related with BMD. This study also showed that different degrees of recurrent hypoxia had different effects on bone metabolism, a finding that required further investigation., (© 2022. The Author(s).)

T-cell reduction is an important characteristic of coronavirus disease 2019 (COVID-19), and its immunopathology is a subject of debate. It may be due to the direct effect of the virus on T-cell exhaustion or indirectly due to T cells redistributing to the lungs. HIV/AIDS naturally served as a T-cell exhaustion disease model for recognizing how the immune system works in the course of COVID-19. In this study, we collected the clinical charts, T-lymphocyte analysis, and chest CT of HIV patients with laboratory-confirmed COVID-19 infection who were admitted to Jin Yin-tan Hospital (Wuhan, China). The median age of the 21 patients was 47 years [interquartile range (IQR) = 40-50 years] and the median CD4 T-cell count was 183 cells/μl (IQR = 96-289 cells/μl). Eleven HIV patients were in the non-AIDS stage and 10 were in the AIDS stage. Nine patients received antiretroviral treatment (ART) and 12 patients did not receive any treatment. Compared to the reported mortality rate (nearly 4%-10%) and severity rate (up to 20%-40%) among COVID-19 patients in hospital, a benign duration with 0% severity and mortality rates was shown by 21 HIV/AIDS patients. The severity rates of COVID-19 were comparable between non-AIDS (median CD4 = 287 cells/μl) and AIDS (median CD4 = 97 cells/μl) patients, despite some of the AIDS patients having baseline lung injury stimulated by HIV: 7 patients (33%) were mild (five in the non-AIDS group and two in the AIDS group) and 14 patients (67%) were moderate (six in the non-AIDS group and eight in the AIDS group). More importantly, we found that a reduction in T-cell number positively correlates with the serum levels of interleukin 6 (IL-6) and C-reactive protein (CRP), which is contrary to the reported findings on the immune response of COVID-19 patients (lower CD4 T-cell counts with higher levels of IL-6 and CRP). In HIV/AIDS, a compromised immune system with lower CD4 T-cell counts might waive the clinical symptoms and inflammatory responses, which suggests lymphocyte redistribution as an immunopathology leading to lymphopenia in COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lin, Lin, Wang, Wen, Xiang, Fan, Li, Wu, Lin, Lin, Sun, Chen, Chen, Lian, Xie, Lin, Xie, Li, Peng, Wang, Lin, Chen, Huang and Fu.)

This Letter proposes a biconical glass rod for generating a cylindrical vector vortex (CVV) beam. Based on the principle of total internal reflection and the cylindrical symmetry structure of the glass rod, a circularly polarized incident beam with a constant phase distribution can be converted into a CVV beam, which possesses both a spatially inhomogeneous polarization and a helical phase distribution. The polarization azimuth of the CVV beam can be tuned with the aid of a polarization rotator composed of two cascade half-wave plates. The design theory is presented, and the feasibility of the design is demonstrated experimentally.

Purpose: Continuous positive airway pressure (CPAP) is the current gold-standard treatment for moderate to severe obstructive sleep apnea (OSA), and upper airway anatomy plays an increasingly important role in evaluating the efficacy of CPAP therapy. The aim of this observational study was to investigate the influence of upper airway anatomy on CPAP titration in OSA patients assessed by computed tomography (CT) during Müller's maneuver., Methods: Consecutive patients under investigation for OSA by undergoing polysomnography and CT scan of the upper airway while awake were enrolled. Successful full-night manual titration was performed to determine the optimal CPAP pressure level for OSA patients in supine position using a nasal mask., Results: A total of 157 subjects (134 males and 23 females) were included. Both apnea-hypopnea index (AHI) and LaSO2 significantly correlated with CPAP titration level, upper airway length (UAL), distance from mandibular plane to hyoid bone (MPH), and neck circumference (all p < 0.05). There were significant positive correlations between CPAP titration level and UAL (r = 0.348, p = 0.000) and MPH (r = 0.313, p = 0.002). Stepwise multiple linear regression analyses were performed to evaluate the independent predictors of AHI, LaSO2, and CPAP titration level. CPAP titration level was identified as an independent explanatory variable for AHI and LaSO2 after adjustment for confounders. Multiple linear regression analyses also indicated that body mass index (BMI) and UAL were independently associated with CPAP titration level (all p < 0.05)., Conclusions: Upper airway abnormalities combined with anthropometric parameters play important roles in CPAP titration for OSA patients, providing additional insight into the factors influencing OSA treatment strategies. UAL and BMI should be taken into consideration when choosing CPAP titration level to improve CPAP compliance., (Copyright © 2020. Published by Elsevier B.V.)

Montelukast is a potent and selective antagonist of the cysteinyl leukotriene receptor 1 subtype (CysLT1) and widely used in the form of oral tablets and granules for asthma prophylaxis and treatment. Recently, due to the pulmonary inhaled administration can limit montelukast distribution in the systemic circulation, avoid the first-pass metabolism and have better therapeutic effects in respiratory disease treatment, explore alternative routes of administration, like delivery of montelukast via an inhaled, is a new research trend for montelukast. The aim of the current study was to develop and validate a simple, accurate, highly sensitive and selective liquid chromatography-tandem mass spectrometry method (LC-MS/MS) for determination of montelukast in an in vitro cell-based pulmonary pharmacokinetics system model, which can be used to be a better understanding the fate of inhaled montelukast in the lungs. In this study, montelukast was extracted by protein precipitation with acetonitrile containing labeled montelukast. The chromatography was performed on an Agilent Eclipse plus C8 column (4.6 mm × 100 mm, 3.5 μm, Darmstadt, Germany) operating at 35 ◦C. The mobile phase consisted of acetonitrile: 20 mM ammonium formate buffer (80: 20, v/v), was delivered at a flow rate of 0.5 mL/min. montelukast and the internal standard were both eluted at 4.2 min. A linear (1/x 2 ) relationship was used to perform the calibration over an analytical range from 0.5 to 600 ng/mL. The intra- and inter-batch precision expressed as CV for four QC samples including LLOQ range from 1.14 % to 6.25 %. The intra- and inter-batch accuracy for four concentrations of montelukast were in the range of 95.19%-104.1%. All the values for accuracy and precision were within the acceptance range. The method met all the bioanalytical method validation requirements by ICH and was suitable for the assay of montelukast which in the in vitro cell-based pulmonary pharmacokinetics system model., Competing Interests: Declaration of Competing Interest The authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The objective of this study was to investigate the serum concentrations of olanzapine in relation to age, sex, and other factors in Chinese patients aged between 10 and 90 years., Methods: Data for 884 olanzapine patients, deposited between 2016 and 2017, were retrieved from the therapeutic drug monitoring database of the Affiliated Brain Hospital of Guangzhou Medical University. The effects of covariates on serum olanzapine concentration, dose-normalized concentration (C/D ratio), and normalized concentration (C/D/weight) were investigated., Results: Generally, male patients had lower olanzapine concentration, C/D ratio, and C/D/weight than female patients (P < 0.001). Smoking and drinking reduced olanzapine concentration, C/D ratio, and C/D/weight (P < 0.001). Coadministration with valproate decreased olanzapine concentration, C/D ratio, and C/D/weight by about 16%, 30%, and 40%, respectively (P < 0.001). Patients younger than 60 years had higher olanzapine concentrations (P < 0.05) but lower C/D ratios and C/D/weight (P < 0.001) than patients older than 60 years. Age was correlated with olanzapine concentration (r = -0.082, P < 0.05), C/D ratio (r = 0.196, P < 0.001), and C/D/weight (r = 0.169, P < 0.001). Sample timing after dose and diagnostic factors also contributed to the olanzapine concentrations. Multiple linear regression analysis revealed significant influences of dosage, age, sex, valproate comedication, smoking, postdose interval, and schizophrenia (vs bipolar affective disorders) on serum olanzapine concentrations., Conclusions: The metabolism of olanzapine may be altered by several factors. Patients characterized with a combination of factors may benefit from therapeutic drug monitoring for the adjustment of olanzapine dose to minimize adverse reactions.

Purpose: This study aimed to investigate the influence of diagnosis, body weight, sex, age, smoking, formulations, and concomitant drugs on steady-state dose-corrected serum concentrations (C/D) of venlafaxine (VEN) and O-desmethylvenlafaxine (ODV)., Methods: A retrospective analysis of therapeutic drug monitoring (TDM) was carried out. Patients' demographic data, therapeutic regimens, and concentrations were collected., Results: We included 91 verified samples from 80 patients. Females had by average 13% smaller body weight, 50% higher C/D of VEN, and VEN + ODV and 25% smaller ODV/VEN than males. Patients >60 years had by average 33-59% higher C/D levels of ODV and VEN + ODV than younger patients. The concomitant use of valproic acid caused an average 51% higher C/D of ODV and a 2.2-fold larger ODV/VEN, while clozapine was related with 40% smaller ratio of ODV/VEN and 38% lower C/D levels of ODV. Positive correlations were detected between valproic acid concentrations and the C/D of VEN and VEN + ODV. In a multiple linear regression analysis, variance in the C/D of VEN + ODV was partly attributed to the daily dose of VEN, sex, age and valproic acid concentration., Conclusion: Our results suggested daily dose of VEN, sex, age, and valproic acid as indicators for the C/D of VEN + ODV in Chinese patients. TDM as a valuable tool was suggested in elderly female patients and patients receiving polypharmacy., (© 2020 John Wiley & Sons Ltd.)

Objective: To search for a method of establishing a reliable mouse model of orchitis and investigate the association of orchitis with the activation of the inflammasome., Methods: We equally randomized 40 adult male KM mice into groups A (sham operation), B (intraperitoneal injection of lipopolysaccharide ［LPS］), C (unilateral testicular injection of glacial acetic acid ［GAA］), and D (unilateral testicular injection of LPS). At 3 weeks after modeling, we measured the sperm concentration and percentage of progressively motile sperm (PMS) in the epididymis by computer-assisted semen analysis, observed the pathological changes in the testis tissue by HE staining, and determined the expressions of the Caspase-1 and interleukin (IL)-1β proteins by Western blot., Results: The sperm concentration in the epididymis was significantly decreased in groups B (［25.74 ± 3.19］ ×10⁶/ml), C (［17.16 ± 4.41］ ×10⁶/ml) and D (［16.92 ± 7.13］ ×10⁶/ml) as compared with that in group A (［28.20 ± 1.63］ ×10⁶/ml) (all P < 0.05), even more significantly in B than in C and D (P < 0.01), and so was PMS in groups B (［29.57 ± 2.16］%), C (［18.10 ± 2.38］%) and D (［7.34 ± 1.63］%) in comparison with group A (［59.34 ± 1.10］%) (P < 0.01), even more significantly in B and C than in D (P < 0.01). Light microscopy revealed different degrees of pathological changes in the testis tissue, most significant in group D, followed by C and B. Both the expressions of Caspase-1 and IL-1β were remarkably up-regulated in groups B, C and D compared with those in group A (P < 0.01), even more markedly in D than in B and C (P < 0.05)., Conclusions: Unilateral testicular injection of LPS is a more efficient method than either unilateral testicular injection of GAA or intraperitoneal injection of LPS for establishing the mouse model of orchitis. Orchitis may be pathologically associated with the activation of the NLRP3 inflammasome.

Summary Alkalis can produce severe tissue injury through liquefaction. Since the liquefaction loosens tissue planes and allows deeper penetration of the agent, alkali burns tend to be more severe than acid burns. Alkaline substances ingestion and inhalation frequently causes damage to the upper respiratory and digestive tract. Initial presentation of airway alkali burn includes oropharyngeal pain, dysphagia, hoarseness and stridor. Patients with a clear history of caustic ingestion or inhalation could always receive proper management. In this paper, a middle aged female presented with acute upper airway obstruction was introduced. The cause of the airway compromise was finally determined to be alkali inhalation 3 weeks ago. By reviewing this special case, the clinical features and management of airway alkali burn was summarized., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Lamotrigine (LTG) is a second-generation anti-epileptic drug widely used for focal and generalized seizures in adults and children, and as a first-line medication in pregnant women and women of childbearing age. However, LTG pharmacokinetics shows high inter-individual variability, thus potentially leading to therapeutic failure or side effects in patients. This prospective study aimed to establish a population pharmacokinetics model for LTG in Chinese patients with epilepsy and to investigate the effects of genetic variants in uridine diphosphate glucuronosyltransferase (UGT) 1A4, UGT2B7, MDR1, ABCG2, ABCC2, and SLC22A1, as well as non-genetic factors, on LTG pharmacokinetics. The study population consisted of 89 patients with epilepsy, with 419 concentrations of LTG. A nonlinear mixed effects model was implemented in NONMEM software. A one-compartment model with first-order input and first-order elimination was found to adequately characterize LTG concentration. The population estimates of the apparent volume of distribution (V/F) and apparent clearance (CL/F) were 12.7 L and 1.12 L/h, respectively. The use of valproic acid decreased CL/F by 38.5%, whereas the co-administration of rifampicin caused an increase in CL/F of 64.7%. The CL/F decreased by 52.5% in SLC22A1 -1222AA carriers. Patients with the ABCG2 -34AA genotype had a 42.0% decrease in V/F, whereas patients with the MDR1 -2677TT and C3435TT genotypes had a 136% increase in V/F. No obvious genetic effect of UGT enzymes was found relative to the concentrations of LTG in Chinese patients. Recommended dose regimens for patients with different gene polymorphisms and comedications were estimated on the basis of Monte Carlo simulations and the established model. These findings should be valuable for developing individualized dosage regimens in adult and adolescent Chinese patients 13-65 years of age.

Purpose: Growing evidence has revealed that nonalcoholic fatty liver disease (NAFLD) is associated with type 2 diabetes. This study aimed to assess the association between glycometabolism and NAFLD in patients with obstructive sleep apnea (OSA)., Methods: Patients with suspected OSA were enrolled consecutively and then underwent polysomnography, liver ultrasound, and biochemical measurements. Logistic regressions were used to identify factors associated with NAFLD., Results: In total, 415 patients were included. The prevalence of NAFLD in the non-OSA, mild OSA, moderate OSA, and severe OSA groups was 37.21%, 69.09%, 68.34%, and 78.08%, respectively. Stepwise logistic regression suggested that percentage of total sleep time spent with oxygen saturation of < 90% (TS90), lowest oxygen saturation (LaSO 2 ), and homeostatic model assessment of insulin resistance (HOMA-IR) were independently associated with NAFLD in all subjects, after adjusting for confounders (odds ratio [OR] = 1.037, p = 0.014; OR = 1.056, p = 0.004; OR = 0.732, p = 0.009; respectively). TS90, LaSO 2 , and HOMA-IR were also independent predictors for NAFLD in patients with mild and moderate OSA, whereas TS90, LaSO 2 , and ODI were independent predictors for NAFLD in patients with severe OSA., Conclusions: There is a relationship between OSA and NAFLD, and the combination of disordered glycometabolism and intermittent hypoxia may act as a "two hit" mechanism to promote the development of NAFLD. Furthermore, intermittent hypoxia alone was an independent predictor for NAFLD in severe OSA patients.

Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.

First principles gyrokinetic simulation of the edge turbulent transport in toroidal plasmas finds a reverse trend in the turbulent transport coefficients under strong gradients. It is found that there exist both linear and nonlinear critical gradients for the nonmonotonicity of transport characteristics. The discontinuity of the transport flux slope around the turning gradient shows features of a second order phase transition. Under a strong gradient the most unstable modes are in nonground eigenstates with unconventional mode structures, which significantly reduces the effective correlation length and thus reverse the transport trend. Our results suggest a completely new mechanism for the low to high confinement mode transition without invoking shear flow or zonal flow.

Objective: To observe the effects of swimming plus medication on the expressions of cytokines in rats with chronic abacterial prostatitis (CAP)., Methods: Forty healthy adult male SD rats were randomly divided into five groups of equal number, normal control, CAP model control, medication, exercise therapy, and exercise + medication. The CAP model was made by Xiaozhiling injection, and at 7 days after modeling, the rats in the medication and exercise + medication groups were treated intragastrically with Qianlie Shutong Capsules (0.016 g/ml) at 20 ml per kg of the body weight qd, those in the exercise therapy and exercise + medication groups were made swim at a regular time once a day, 35 minutes on the first day and 5 minutes more on the second until 50 minutes once, for 4 successive weeks, and those in the normal control, model control and exercise therapy groups received normal saline only. After 14 and 28 days of treatment, all the rats were killed and their prostates harvested for observation of histopathological changes and determination of the expressions of TNF- α, IL-1β and IL-6 in the prostatic tissue homogenate by ELISA., Results: After 14 days of treatment, the expression levels of TNF-α, IL-1β and IL-6 were significantly elevated in the groups of CAP model control (［183.08±8.07］ pg/ml, ［57.55±3.53］ pg/ml and ［256.15±13.95］ ng/L), medication (［118.49±8.06］ pg/ml, ［42.64±4.64 ］ pg/ml and ［200.74±9.33］ ng/L), exercise therapy (［169.63±10.64］ pg/ml, ［50.45±5.71］ pg/ml and ［245.23±6.49］ ng/L), and exercise + medication (［107.82±7.81］ pg/ml, ［40.35±6.93］ pg/ml and ［187.04±10.85］ ng/L) as compared with those in the normal control (［20.36±1.82］ pg/ml, ［14.64±1.91］ pg/ml and ［70.58±2.09］ ng/L) (P<0.05). At 28 days, the levels of TNF- α, IL-1β, IL-6 were remarkably lower in the exercise + medication group (［29.30±3.78］ pg/ml, ［16.91±1.24］ pg/ml and ［ 88.65±6.74］ ng/L) than in the medication group (［39.67±3.19］ pg/ml, ［26.27±3.49］ pg/ml and ［110.26±6.33］ ng/L) (P<0.05) and close to those of the normal control group (［19.34±1.76］ pg/ml, ［13.68±1.06］ pg/ml and ［71.34±2.50］ ng/L). During the treatment, no obvious pathological changes were found in the prostate tissue of the normal control rats, while significant chronic prostatic inflammation was observed in the CAP models, and the inflammation was relieved in different degrees after intervention, most significantly in the exercise + medication group., Conclusions: Swimming can relieve prostatic inflammation and swimming plus medication can effectively reduce the expressions of cytokines and alleviate histological damage in the prostatic tissue of CAP rats.

Background: The purpose of this observational study was to investigate the relationship between upper-airway configuration assessed by CT imaging during the Müller maneuver state and the severity of obstructive sleep apnea syndrome (OSAS)., Methods: A total of 358 snoring subjects who underwent standard polysomnography and upper-airway configuration by using CT imaging were enrolled. According to the apnea-hypopnea index (AHI), subjects were classified into 4 groups: snoring group (simple snoring), AHI < 5; mild OSAS, 5 ≤ AHI < 15; moderate OSAS, 15 ≤ AHI < 30; and severe OSAS, AHI ≥ 30. We also divided the upper airway into 3 parts, named the nasopharynx, oropharynx, and hypopharynx, from the CT scan and evaluated the minimal cross-sectional area (mCSA) and the shape of each airway level and calculated upper-airway length and distance from mandibular plane to hyoid bone (MPH)., Results: Multivariate logistic stepwise regression analysis identified body mass index (BMI), mCSA of nasopharynx, upper-airway length, and MPH as risk factors for the severity of OSAS. When subdivided for BMI and sex, upper-airway length was a risk factor for OSAS in non-obese (BMI < 27 kg/m 2 ) and male subjects, and MPH was a risk factor only in obese (BMI ≥ 27 kg/m 2 ) subjects. Meanwhile, mCSA of nasopharynx was significantly associated with the severity of OSAS independent of BMI., Conclusions: Subjects with severe OSAS have more significant abnormalities of the upper airway. Obesity, mCSA of nasopharynx, upper-airway length, and MPH may contribute to the severity of OSAS. Obesity and sex should be taken into account when evaluating the abnormalities of upper-airway anatomy in snorers and patients with OSAS., (Copyright © 2016 by Daedalus Enterprises.)

The international cooperated research projects of the Human Microbiome Project (HMP) and Metagenomics of The Human Intestinal Tract (MetaHIT) were officially launched in 2007, which indicated the era of metagenomics research of microorganisms in human gastrointestinal tract had been coming. Each human body is a superorganism which is composed of 90% commensal microorganisms, especially the intestinal microorganisms. The intestinal microorganisms play an important role on health maintenance since they are involved in the absorption and metabolism of nutrients in the human bodies. Herein, we review the research progress in the mechanism of intestinal microorganisms in human diseases. Our purpose is to provide novel ideas on human health and therapeutic targets of diseases.

A large number and wide varieties of microorganisms colonize in the human gastrointestinal tract. They construct an intestinal microecological system in the intestinal environment. The intestinal symbiotic flora regulates a series of life actions, including digestion and absorption of nutrient, immune response, biological antagonism, and is closely associated with the occurrence and development of many diseases. Therefore, it is greatly essential for the host's health status to maintain the equilibrium of intestinal microecological environment. After effective compositions of traditional Chinese medicines are metabolized or biotransformed by human intestinal bacteria, their metabolites can be absorbed more easily, and can even decrease or increase toxicity and then exhibit significant different biological effects. Meanwhile, traditional Chinese medicines can also regulate the composition of the intestinal flora and protect the function of intestinal mucosal barrier to restore the homeostasis of intestinal microecology. The relevant literatures in recent 15 years about the interactive relationship between traditional Chinese medicines and gut microbiota have been collected in this review, in order to study the classification of gut microflora, the relationship between intestinal dysbacteriosis and diseases, the important roles of gut microflora in intestinal bacterial metabolism in effective ingredients of traditional Chinese medicines and bioactivities, as well as the modulation effects of Chinese medicine on intestinal dysbacteriosis. In addition, it also makes a future prospect for the research strategies to study the mechanism of action of traditional Chinese medicines based on multi-omics techniques., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Objective: To observe the characteristics of acoustic parameters of 21 patients with amyotrophic lateral sclerosis (ALS) complaining of dysarthria and to explore the possibility and clinical value of Multi-Dimensional Voice Program (MDVP) on aseessing the patient's voice., Methods: The clinical data and speech intelligibility of each of the 21 patients with ALS complaining of dysarthria were collected. All the 21 patients with ALS and 44 normal subjects were suggested to pronounce the vowel [a:]. The voice samples were collected and analyzed by Multi Dimensional Voice Program. The data were compared to detect the difference between the two groups., Results: Speech intelligibility of 10 in the 21 patients was above 97% including 5 patients whose scores were 100%. It seemed that the speech intelligibility score was not related with the duration of the disease and the on-set part. The values of noise to harmonic ratio (NHR) of both the light and the severe damage to the speech group were higher than those of the control group with significant difference (P<0.05).Significant difference was noticed between the severe damage to the speech group and control group in Jitter., Conclusion: Multi Dimensional Voice Program could be used to analyze the characteristics of acoustic parameters of patients with ALS patients complaining of dysarthria. There was more noise composition in the voice of the patients with dysarthria. NHR seemed to be the sensitive and stable parameter. Especially in patients whose speech intelligibility were affected severely, more acoustic parameters were detected with significant difference.

Objective: To evaluate the relationship between high sensitivity C-reactive protein (hs-CRP) level and the severity of obstructive sleep apnea-hypopnea syndrome (OSAHS) in non-obese patients., Methods: A total of 65 patients with suspected OSAHS were recruited. Those with a history of cardiovascular or cerebrovascular events, arterial hypertension, chronic obstructive pulmonary disease, diabetes mellitus and smoking were excluded. All subjects were examined by polysomnography. Subjects with an apnea-hypopnea index (AHI) ≥ 5 were considered to have OSAHS. They were divided into mild, moderate and severe OSAHS groups and those with an AHI < 5 were accepted into the control group. The serum level of hs-CRP, a biomarker for cardiovascular disease, was measured with peripheral venous blood samples., Results: There were 53 males and 12 females with a mean age 44.3 ± 12.2 years and a body mass index (BMI) <25 kg/m(2). The serum levels of hs-CRP were significantly higher in OSAHS patients than those of the controls (geometric mean [95% confidence interval] 0.416 [0.288-0.600] vs 0.749 [0.559-1.003] mg/L, P < 0.05). Mean levels of hs-CRP did not differ between the group with mild-to-moderate OSAHS and the control group. However, the severe OSAHS group had a higher level of hs-CRP than the control group (P = 0.004). A significant positive relationship existed between hs-CRP and AHI (r = 0.407, P = 0.001) . According to stepwise multivariate analysis, only AHI was a reliable predictor for elevated serum level of hs-CRP among all these related factors (R(2) = 0.166, P = 0.001)., Conclusion: The severity of OSAHS is associated with an elevated serum level of hs-CRP in non-obese patients.

Focal cerebral ischemia results in an increased expression of matrix metalloproteinase-9 (MMP-9), which induces vasogenic brain edema via disrupting the blood-brain barrier (BBB) integrity. Recent studies from our laboratory showed that baicalin reduces ischemic brain damage by inhibiting inflammatory reaction and neuronal apoptosis in a rat model of focal cerebral ischemia. In the present study, we first explored the effect of baicalin on the neuronal damage, brain edema and BBB permeability, then further investigated its potential mechanisms. Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (MCAO). Baicalin was administrated by intraperitoneally injected twice at 2 and 12 h after the onset of MCAO. Neuronal damage, brain edema and BBB permeability were measured 24 h following MCAO. Expression of MMP-9 protein and mRNA were determined by western blot and RT-PCR, respectively. Expression of tight junction protein (TJP) occludin was detected by western blot. Neuronal damage, brain edema and BBB permeability were significantly reduced by baicalin administration following focal cerebral ischemia. Elevated expression of MMP-9 protein and mRNA were significantly down-regulated by baicalin administration. In addition, MCAO caused the decreased expression of occludin, which was significantly up-regulated by baicalin administration. Our study suggested that baicalin reduces MCAO-induced neuronal damage, brain edema and BBB permeability, which might be associated with the inhibition of MMP-9 expression and MMP-9-mediated occludin degradation.

The title compound, C(23)H(18)BrN, was synthesized by the reaction of 4-bromo-benzaldehyde, naphthalen-2-amine and cyclo-hexa-none in tetra-hydro-furan, catalyzed by iodine. The saturated six-membered ring adopts a half-chair conformation, and the four vicinal rings form a helical conformation, which results in a significant deviation from planarity for the pyridine ring. In the crystal, a weak C-H⋯π inter-action occurs, leading to inversion dimers.

An intrinsic plastic Cu(45)Zr(46)Al(7)Ti(2) bulk metallic glass (BMG) with high strength and superior compressive plastic strain of up to 32.5% was successfully fabricated by copper mold casting. The superior compressive plastic strain was attributed to a large amount of randomly distributed free volume induced by Ti minor alloying, which results in extensive shear band formation, branching, interaction and self-healing of minor cracks. The mechanism of plasticity presented here suggests that the creation of a large amount of free volume in BMGs by minor alloying or other methods might be a promising new way to enhance the plasticity of BMGs.

Objective: To explore the quality and quantity of glutamate(Glu) on the auditory pathway of inferior colliculus when exposed to conditioning noise or traumatic sound to find the relationship between the change of neurotransmitters and the protection of hearing, and the mechanism in the phenomena., Methods: Twenty Sprague-Dawley rats were divided into four groups: control group, conditioning group, intensive noise group and combining group. The hearing function was measured by ABR. Glu was detected by microdialysis and HPLC., Results: The ABR levels after exposure were (47.0+/-2.7) dB SPL (intensive noise group ),(31.0+/-2.2) dB SPL (conditioning group ) and (36.0+/-2.2) dB SPL (combining group ).The levels of Glu were (310.5+/-78.5)x 10(-7)mol/L (intense noise group ),(162.9+/-64.1)x10(-7)mol/L (conditioning group ); (113.6+/-38.1)x10(-7)mol/L (combining group),(56.3+/-23.9)x10(-7)mol/L (control group)., Conclusion: The level of Glu on the auditory pathway of inferior colliculus was higher when exposed to noise . Glu was exhausted when given conditioning sound, and the level of Glu was lower when given following intense noise. High level of Glu can damage hearing, so exhaustion of Glu in sound condition may contribute to the protection.

The pressure-induced phase transition of rutile-structured TiO2 was investigated by in-situ Raman spectrum method in a laser-heated diamond anvil cell (DAC). The experiment was conducted at 35 GPa under quasihydrostatic conditions using argon as medium. At room temperature, the rutile-type TiO2 begins to transform to baddeleyite-type phase at 13.4 GPa and completes at 21 GPa, and this new high-pressure structure retains up to 35 GPa, the upmost pressure used in this study. At the pressure of 29.4 GPa the sample of baddeleyite-type TiO2 was heated by an YAG laser to about 1 000-1500 degrees C, and then the baddeleyite phase transformed to a Pbca phase. The Pbca phase was heated again at 35.0 GPa and it was still stable. The sample then began to be decompressed, and the Pbca phase of TiO2 transformed to baddeleyite structure at 26.3 GPa, which stayed stable to 11.4 GPa. The formation of Pbca phase from baddeleyite phase needs the condition of high temperature, it transforms back to badde-leyite structure completely at pressure of a little below that on its formation, which suggests the boundary of the two phases can be determined at about 28 GPa. At 7. 6 GPa, and the Raman spectrum shows the characteristics of the mixture of two phases of baddeleyite-type and alpha-PbO2-type, which indicates that the baddeleyite phase transforms to alpha-PbO2 phase at about 7 GPa. The alpha-PbO2-type TiO2 is metastable under ambient condition.

Raman scattering studies of the stretching band from liquid water have been conducted up to 600 MPa at 290 K. It is shown that (r1)(max) decreases with increasing pressure initially and reaches the minimum at about 200 MPa, and increases at higher pressure up to about 400 MPa, then decreases with increasing pressure up to 600 MPa. And this is also in accordance with the behavior of r(oo) under pressure. The authors conclude that, just like ice phase transition ice ( I h) --> ice(II) --> ice (V), there also probably exists water phase transition water ( I h) --> water (III) --> water (V).