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Hai-Hua Chuang,1– 3 Chao-Yung Wang,4 Li-Pang Chuang,5 Yu-Shu Huang,6 Hsueh-Yu Li,7 Tuan-Jen Fang,7 Rong-Ho Lin,2 Li-Ang Lee3,7 1Department of Family Medicine, Chang Gung Memorial Hospital, Linkou Main Branch, Chang Gung University, Taoyuan, Taiwan; 2Department of Industrial Engineering and Management, National Taipei University of Technology, Taipei, Taiwan; 3School of Medicine, National Tsing Hua University, Hsinchu, Taiwan; 4Department of Cardiology, Chang Gung Memorial Hospital, Linkou Main Branch, Chang Gung University, Taoyuan, Taiwan; 5Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Linkou Main Branch, Chang Gung University, Taoyuan, Taiwan; 6Department of Child Psychiatry, Chang Gung Memorial Hospital, Linkou Main Branch, Chang Gung University, Taoyuan, Taiwan; 7Department of Otorhinolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Linkou Main Branch, Chang Gung University, Taoyuan, TaiwanCorrespondence: Li-Ang Lee, Department of Otorhinolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Linkou Main Branch, No. 5, Fuhsing Street, Guishan District, Taoyuan, 33305, Taiwan, Tel +886 33281200 ext. 3972, Fax +886 33979361, Email 5738@cgmh.org.twBackground: Obstructive sleep apnea (OSA) and obesity are both directional risk factors of hypertension. Chronic intermittent hypoxemia (IH) is a commonly observed pathophysiological mechanism involved in multiple comorbidities of OSA. However, their interactions are not well understood in children. This study aimed to investigate the associations of IH indexes (oxygen desaturation index 3% [ODI3], mean peripheral oxygen saturation [SpO2], least SpO2, and time with SpO2 < 85%), apnea-hypopnea index, and weight status with hypertension in a sample of pediatric OSA patients.Methods: The medical records of 365 pediatric OSA patients were retrospectively reviewed in this cross-sectional study. Demographics, anthropometrics, standard in-laboratory polysomnography, and nocturnal blood pressure were collected. Multivariate logistic regression with forward selection was used to identify independent predictors of hypertension.Results: Multivariate logistic regression analysis showed that ODI3 (odds ratio [OR] = 1.02, 95% confidence interval [CI] = 1.01– 1.03) and body mass index z-score (OR = 1.34, 95% CI = 1.12– 1.60) were independent continuous predictors of pediatric hypertension, whilst severe OSA (OR = 2.62, 95% CI = 1.60– 4.29) and overweight/obesity (OR = 2.63, 95% CI = 1.59– 4.34) were independent categorical predictors. Traditional risk factors including male sex (OR = 2.33, 95% CI = 1.02– 5.33), late childhood/adolescence (OR = 1.98, 95% CI = 1.01– 3.88), and overweight/obesity (OR = 2.97, 95% CI = 1.56– 5.67) combined with sleep hypoxemia (least SpO2 ≤ 95%) (OR = 2.24, 95% CI = 1.16– 4.04) predicted hypertension (R2 = 0.21) in the severe IH subgroup (n = 205), while the no/mild IH subgroup (n = 160) had an entirely different predictor, severe OSA (OR = 3.81, 95% CI = 1.49– 9.74) (R2 = 0.07).Conclusion: The close relationships among IH, overweight/obesity, and hypertension highlight the importance of reducing IH and body weight in children with OSA.Keywords: children, oxygen desaturation index, intermittent hypoxemia, obesity, obstructive sleep apnea, predictive model

Background: Hepatic fibrosis (HF) runs through multiple stages of liver diseases and promotes these diseases progression. Oxysophoridine (OSR), derived from Sophora alopecuroides l., is a bioactive alkaloid that has been reported to antagonize alcoholic hepatic injury. However, whether OSR suppresses HF and the mechanisms involved in Nrf2 remain unknown., Purpose: Since the dysregulation of inflammation and oxidative stress is responsible for the excessive accumulation of extracellular matrix (ECM) and fibrosis in the liver. We hypothesized that OSR may attenuate HF by inhibiting inflammation and oxidative stress through activating Nrf2 signaling., Methods: In this study, we employed LPS-stimulated HSC-T6 cells, RAW264.7 cells, and a CCl 4 -induced C57BL/6 mouse fibrotic model to evaluate its suppressing inflammation and oxidative stress, as well as fibrosis., Results: The result showed that OSR significantly reduced α-SMA and TGF-β 1 at a low dose of 10 μM in vitro and at a dose of 50 mg/kg in vivo, which is comparable to Silymarin, the only Chinese herbal active ingredient that has been marketed for anti-liver fibrosis. Moreover, OSR effectively suppressed the expression of iNOS at a dose of 10 μM and COX-2 at a dose of 40 μM, respectively. Furthermore, OSR demonstrated inhibitory effects on the IL-1β, IL-6, and TNF-α in vitro and almost extinguished cytokine storm in vivo. OSR exhibited antioxidative effects by reducing MDA and increasing GSH, thereby protecting the cell membrane against oxidative damage and reducing LDH release. Moreover, OSR effectively upregulated the protein levels of Nrf2, HO-1, and p62, but decreased p-NF-κB p65, p-IκBα, and Keap1. Alternatively, mechanisms involved in Nrf2 were verified by siNrf2 interference, siNrf2 interference revealed that the anti-fibrotic effect of OSR was attributed to its activation of Nrf2., Conclusion: The present study provided an effective candidate for HF involved in both activation of Nrf2 and blockage of NF-κB, which has not been reported in the published work. The present study provides new insights for the identification of novel drug development for HF., Competing Interests: Declaration of competing interest We all authors declare we have no competing interests about their work (financial and non-financial). All the authors listed have approved the manuscript., (Copyright © 2024. Published by Elsevier GmbH.)

Data scarcity is one of the most critical issues impeding the development of prediction models for chemical effects. Multitask learning algorithms leveraging knowledge from relevant tasks showed potential for dealing with tasks with limited data. However, current multitask methods mainly focus on learning from datasets whose task labels are available for most of the training samples. Since datasets were generated for different purposes with distinct chemical spaces, the conventional multitask learning methods may not be suitable. This study presents a novel multitask learning method MTForestNet that can deal with data scarcity problems and learn from tasks with distinct chemical space. The MTForestNet consists of nodes of random forest classifiers organized in the form of a progressive network, where each node represents a random forest model learned from a specific task. To demonstrate the effectiveness of the MTForestNet, 48 zebrafish toxicity datasets were collected and utilized as an example. Among them, two tasks are very different from other tasks with only 1.3% common chemicals shared with other tasks. In an independent test, MTForestNet with a high area under the receiver operating characteristic curve (AUC) value of 0.911 provided superior performance over compared single-task and multitask methods. The overall toxicity derived from the developed models of zebrafish toxicity is well correlated with the experimentally determined overall toxicity. In addition, the outputs from the developed models of zebrafish toxicity can be utilized as features to boost the prediction of developmental toxicity. The developed models are effective for predicting zebrafish toxicity and the proposed MTForestNet is expected to be useful for tasks with distinct chemical space that can be applied in other tasks.Scieific contributionA novel multitask learning algorithm MTForestNet was proposed to address the challenges of developing models using datasets with distinct chemical space that is a common issue of cheminformatics tasks. As an example, zebrafish toxicity prediction models were developed using the proposed MTForestNet which provide superior performance over conventional single-task and multitask learning methods. In addition, the developed zebrafish toxicity prediction models can reduce animal testing., (© 2024. The Author(s).)

Objectives : Cervical disc herniation (CDH) leads to pain, numbness, and potential disability. Percutaneous endoscopic cervical discectomy (PECD) offers an anterior or posterior approach. This study aims to compare postoperative disc height and angle changes one year after PECD, considering both approaches. Methods : We retrospectively reviewed the data from patients with CDH who underwent PECD from October 2017 to July 2022. Cervical disc height was measured using the preoperative and one-year postoperative magnetic resonance imaging (MRI) examinations. Lordotic angle (LA), global alignment angle (GAA), segmental alignment angle (SAA), and slippage distance (SD) at the surgical level were measured on radiographs in the neutral, flexion, and extension positions. Results : Thirty-eight patients who underwent posterior PECD (PPECD) and five patients who underwent anterior PECD (APECD) were included in the evaluation. The mean age of the patients was 47.4 years (range: 29-69 years). There was a significant difference in the preoperative and one-year postoperative GAA and SAA in extension in the PPECD group ( p = 0.003 and 0.031, respectively). The mean decreased disc height one-year postoperative was 1.30 mm in the APECD group and 0.3 mm in the PPECD group by MRI. A significant disc height decrease was observed in the APECD group ( p < 0.001). Conclusions : Treating CDH with PPECD or APECD is feasible, as it can relieve symptoms and reduce disability. Stability remained unaffected during the first year after surgery, even though there was an increase in angulation during extension. Despite a significant decrease in disc space following APECD, patients reported significant symptom improvement and no new symptoms.

Objective: This retrospective study was designed to evaluate the incidence and predisposing factors of heterotopic ossification (HO) after cervical disc arthroplasty (CDA) with a specific implant at 1 and 2 levels, and to investigate the biomechanical effects related to HO. The study goal was to identify ways to reduce the likelihood of HO formation after surgery., Methods: The study included patients who underwent only 1- or 2-level CDA with the Baguera C disc between November 2014 and December 2021 at a single medical center. All patients were operated on by the same neurosurgeon. The surgical indication included 1-level or 2-level disc herniation between C3 and C7 with radiculopathy, myelopathy, or both, with minimal spondylosis. The various factors were assessed by evaluating plain radiographs and cervical CT scans. The presence of HO was evaluated at different intervals postsurgery, and HO severity was graded using the McAfee classification., Results: Of 107 patients who underwent CDA, 47 (43.9%) had HO at 63 of 171 levels (36.8%). Most cases with HO were grade 1, and no grade 4 was observed. Statistically significant risk factors for HO were the length of endplate coverage ratio and inferior anterior residual exposed endplate (AREE); sex, age, implant height and width, shell angle, and pre- and postoperative functional spinal unit (FSU) angle were not significant. More AREE and greater kyphotic postoperative FSU angle in the flexion position were significant factors differentiating HO grades 0 and 1 from grades 2 and 3. Furthermore, the non-HO group showed a trend of higher range of motion at any postoperative time compared to the HO group, especially at 1 month after surgery., Conclusions: The HO incidence after CDA was correlated with the residual length of endplate coverage and inferior AREE. Additionally, the AREE and kyphotic postoperative FSU angle in the flexion position were associated with HO grade progression. Patients with HO also showed a trend of lower range of motion at 1 month after surgery. Using an adequately sized implant and encouraging neck motion may help prevent HO development and progression.

Background : Cervical disc arthroplasty (CDA) is currently used instead of fusion to preserve cervical spine motion. Cervical implant subsidence is a potential complication after CDA. Methods : Radiological measurements were recorded via patient anteroposterior and lateral radiographs in the neutral position. Subsidence was defined as a decrease of 3 mm or more in functional spinal unit height (FSUH) from which was measured on a post-operative (OP) radiograph. Results : This study included 104 patients who underwent 153 CDA levels with the Bryan Disc. Approximately one-quarter of the implants (22.9%) showed subsidence. Binary logistic regression analysis indicated that pre-OP mean disc height (DH) was identified as an independent risk factor for subsidence in multivariate analysis (0.151, 95% Confidence Interval 0-0.073, p = 0.018). Receiver operating characteristic curve analysis (area under the curve = 0.852, sensitivity 84.7%, specificity 77.1%) revealed a cut-off value of 4.48 mm for pre-OP Mean-DH in the risk for implant subsidence. Conclusions : In this study, the subsidence rate significantly increased when the implants were oversized beyond a pre-OP Mean-DH of approximately >4 mm. Moreover, the implant subsidence incidence was higher than that reported in previous studies. This is possibly due to endplate over-preparation or disc space over-distraction during placement at the same height as the Bryan Disc (8.5 mm).

Aim: An estimated 88% of rheumatoid arthritis (RA) patients experience various degrees of cervical spine involvement. The excessive movement of the atlantoaxial joint, which connects the occiput to the upper cervical spine, results in atlantoaxial instability (AAI). AAI stabilization is usually achieved by C1 lateral mass-to-C2 pedicle screw-rod fixation (LC1-PC2 fixation), which is technically challenging in RA patients who often show destructive changes in anatomical structures. This study aimed to analyze the clinical results and operative experiences of C1-C2 surgery, with emphasis on the advancement of image-guided surgery and augmented reality (AR) assisted navigation., Methods: We presented our two decades of experience in the surgical management of AAI from April 2004 to November 2022., Results: We have performed surgery on 67 patients with AAI, including 21 traumatic odontoid fractures, 20 degenerative osteoarthritis, 11 inflammatory diseases of RA, 5 congenital anomalies of the os odontoideum, 2 unknown etiologies, 2 movement disorders, 2 previous implant failures, 2 osteomyelitis, 1 ankylosing spondylitis, and 1 tumor. Beginning in 2007, we performed LC1-PC2 fixation under C-arm fluoroscopy. As part of the progress in spinal surgery, since 2011 we used surgical navigation from presurgical planning to intraoperative navigation, using the preoperative computed tomography (CT) -based image-guided BrainLab navigation system. In 2021, we began using intraoperative CT scan and microscope-based AR navigation., Conclusion: The technical complexities of C1-C2 surgery can be mitigated by CT-based image-guided surgery and microscope-based AR navigation, to improve accuracy in screw placement and overall clinical outcomes, particularly in RA patients with AAI., (© 2023 The Authors. International Journal of Rheumatic Diseases published by Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objectives: Heterotopic ossification (HO), a major cause of dysfunction after disc arthroplasty (CDA). The aim of this study was to determine the cut value of the residual exposed endplate (REE) ratio and to predict the development of posterior HO after Bryan CDA., Methods: This retrospective study investigated the relationship between the REE ratio and posterior HO formation after Bryan CDA. Consecutive adult patients who underwent 1- or 2-level Bryan CDA by a single neurosurgeon between 2006 and 2016 with at least two years follow-up were included. Postoperative radiographic analysis and measurement were performed to obtain the REE ratio and the HO grade., Results: Of 249 patients with 384 surgical levels who underwent Bryan CDA during the study period, 114 (45.8 %) received 1-level CDA and 135 (54.2 %) received 2-level CDA. Lateral radiographs showed that 169 implants (44 %) had posterior HOs in all grades after two years or more of follow up and 14 implants (3.64 %) had severe HO (McAfee grades 3 and 4). In 329 implants (85.7 %), a comparison of radiographs to CT examination of HO grading showed a substantial relationship. Using area under the curve (AUC) analysis, a REE ratio >9 %, with 65.1 % sensitivity and 86.5 % specificity, was the cut point for posterior HO formation., Conclusions: REE is highly correlated with the development of postoperative posterior HO after Bryan CDA, regardless of the level of implantation. An undersized implant causing a REE ratio >9 % is a predictor of postoperative posterior HO formation after cervical Bryan CDA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Dietary behavior is a main contributing yet modifiable factor to the body weight status of children and may be involved in the pathophysiology of childhood obstructive sleep apnea (OSA). This study aimed to investigate the dietary profile of pediatric OSA patients, effects of educational counseling after adenotonsillectomy, and predictor for disease resolution., Methods: This observational study included 50 pediatric OSA patients undergoing adenotonsillectomy with routine educational counseling (Group 1), 50 pediatric OSA patients undergoing adenotonsillectomy without formal educational counseling (Group 2), and 303 healthy children without OSA (Control). The three groups were matched by age. The consumption frequency of 25 food items/groups was assessed by the Short Food Frequency Questionnaire. Quality of life was evaluated by the OSA-18 questionnaire. Sleep architecture and OSA severity were measured by standard polysomnography. Between- and within-group comparisons were analyzed by non-parametric approaches and generalized estimating equations. Prediction of disease recovery was performed by multivariable logistic regression models., Results: Group 1 children consumed fruit drinks with sugar, vegetables, sweets, chocolate, rice, and noodles more frequently than Control Group children. At baseline, the distributions of sex, weight status, OSA-18 scores, and polysomnographic variables were comparable between Group 1 and Group 2. After a 12-month follow-up, Group 1 had better improvements in physical suffering, caregiver concerns, sleep architecture, and mean peripheral oxygen saturation compared to Group 2. Furthermore, Group 1 no longer had excessive consumption of fruit drinks with sugar, chocolate, and noodles; however, food consumption frequencies did not change significantly. Notably, younger age and reduced intake of butter/margarine on bread and noodles were independent predictors of cured OSA in Group 1., Conclusion: The present study preliminarily characterized an unhealthy dietary profile among pediatric OSA patients and suggested that routine educational counseling in addition to adenotonsillectomy yielded some clinical benefits. Certain items/groups of food frequencies may be associated with disease recovery and further investigations are warranted., 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 © 2023 Chuang, Lin, Hsu, Chuang, Li, Fang, Huang, Yang, Lee, Kuo, Yang and Lee.)

Background: Pediatric hypertension contributes to adulthood hypertension and target organ damage. Obesity is a well-known predictor for pediatric hypertension; however, the relationship between physical fitness and blood pressure (BP) is unclear among children. This study aimed to compare the differences in demographics, anthropometrics, and physical fitness across BP subgroups and investigate whether physical fitness was related to pediatric hypertension independent of weight status., Methods: This quantitative, cross-sectional study investigated demographic, anthropometric, physical fitness, and BP measures among 360 healthy school-aged children. Continuous variables were compared across BP subgroups with the one-way analysis of variance. Mediation and moderation analyses were used to explore the mechanism. Multivariable regression models were used to assess independent associations for hypertension., Results: There were 177 (49.2%), 37 (10.3%), and 146 (40.6%) children in the normotensive, elevated BP, and hypertensive subgroups, respectively. The hypertensive subgroup had higher body mass index (BMI) and waist/height ratio percentiles and performed worse in 800-m run, standing long jump (SLJ), and 1-min sit-ups than the normotensive subgroup. Furthermore, the 800-m run percentile (total effect: β = 0.308, standard error = 0.044, p < 0.001) and sit and reach percentile (total effect: β = 0.308, standard error = 0.044, p < 0.001) mediated the relationship between the BMI percentile and systolic BP percentile; the SLJ percentile was directly associated with the diastolic BP percentile (β,-0.197, 95% confidence interval,-0.298-0.097; p < 0.001). The parsimonious model of multivariable regression models revealed that the SLJ percentile (adjusted exp (β), 0.992, 95% confidence interval, 0.985-0.999; p = 0.042) and BMI percentile (adjusted exp (β), 1.024, 95% confidence interval, 1.016-1.032; p < 0.001) were two independent predictors for pediatric hypertension., Conclusion: Physical fitness mediates the relationship between anthropometric and BP measures. The SLJ percentile is associated with pediatric hypertension independent of the BMI percentile. Proactive screening and health promotion for not only healthy weight status but also good physical fitness may be beneficial for BP control among school-aged students., 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 © 2023 Chuang, Cherng, Lin, Lee, Hsu and Lin.)

Objectives: The objectives of this study were to identify the risk factors and incidence of anterior bone loss (ABL) after Baguera C cervical disc arthroplasty (CDA) and identify whether design differences in artificial discs affect ABL., Methods: In this retrospective radiological review of patients who underwent single-level Baguera C CDA in a medical center, the extent of ABL and the following radiological parameters were recorded: global and segmental alignment angle, lordotic angle (or functional spinal unit angle), shell angle, global range of motion (ROM), and ROM of the index level. ABL at the index level was grade 0-2. Grade 0 was defined as no remodeling, grade 1 as spur disappearance or mild change in body contour, and grade 2 as obvious bone regression with Baguera C Disc exposure., Results: Combining grade 1 and grade 2, ABL was found in 56 upper adjacent vertebrae and 52 lower adjacent vertebrae of the 77 patients. Only 18 patients (23.4%) had no ABL. Shell angle differed significantly between ABL grades of both the upper and lower adjacent level: 0.0° in grade 0 and 1 ABL vs. 2.0° in grade 2 ABL of the upper adjacent level ( p < 0.05); and 0.0° in grade 0 and 1 ABL vs. 3.5° in grade 2 ABL of the lower adjacent level ( p < 0.05). A female predominance of ABL was found. Hybrid surgery and artificial disc size were also related to ABL., Conclusions: ABL is more common in Baguera C Disc arthroplasty than Bryan Disc arthroplasty. Larger shell angle was related to ABL after CDA with Baguera C Discs, which may indicate that shell angle is pivotal in determining the incidence of ABL after CDA. Females had more ABL with Baguera C Disc arthroplasty; this might be related to shorter endplate lengths as well as a smaller endplate-implant mismatch., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Chih-Chang Yang et al.)

The effect of spinal anatomical anomalies on the efficacy of percutaneous endoscopic lumbar discectomy (PELD) for disc herniation repair is unclear. This retrospective review aims to assess the safety and effectiveness of PELD for treating L5-S1 disc herniation with a range of characteristics and to determine the prevalence of lumbosacral transitional vertebrae (LSTV) anatomical anomalies to facilitate pre-surgical planning. From July 2005 to June 2019, 345 patients with L5-S1 disc herniations were treated with PELD. The primary outcome was 1-year postoperative visual analogue scale scores for low back and lower limb pain. The secondary outcomes included the surgical approach used, lumbosacral bony anomalies, presence of a ruptured disc or severely calcified disc, pediatric lumbar disc herniation, recurrent disc herniation management, and the long-term outcome. visual analogue scale scores for most patients were significantly improved after surgery. The prevalence of LSTVs was 4.05% (14/345 patients) in lumbar sacralization and 7.53% (26/345 patients) in sacral lumbarization. The prevalence of ruptured and severely calcified discs was 18.55% (64/345) and 5.79% (20/345), respectively. The prevalence of pediatric lumbar disc herniation was 2.02% (7/345). The recurrence rate was 4.34% (15/345). Two durotomy cases without sequelae and 8 cases of lower limb dysesthesia lasting longer than 3 months postoperatively were reported. PELD is safe and effective for treating L5-S1 disc herniation, including cases complicated by calcified lumbar disc herniation, disc rupture with migration, and the presence of LSTV. Appropriate imaging is essential to identify case-specific factors, including the prevalent LSTV anatomical anomalies, before surgery., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Gold nanoparticles (AuNPs) are well known to interact with cells, leading to different cell behaviors such as cell proliferation and differentiation capacity. Biocompatibility and biological functions enhanced by nanomedicine are the most concerning factors in clinical approaches. In the present research, AuNP solutions were prepared at concentrations of 1.25, 2.5, 5 and 10 ppm for biocompatibility investigations. Ultraviolet-visible spectroscopy was applied to identify the presence of AuNPs under the various concentrations. Dynamic Light Scattering assay was used for the characterization of the size of the AuNPs. The shape of the AuNPs was observed through a Scanning Electron Microscope. Afterward, the mesenchymal stem cells (MSCs) were treated with a differentiation concentration of AuNP solutions in order to measure the biocompatibility of the nanoparticles. Our results demonstrate that AuNPs at 1.25 and 2.5 ppm could significantly enhance MSC proliferation, decrease reactive oxygen species (ROS) generation and attenuate platelet/monocyte activation. Furthermore, the MSC morphology was observed in the presence of filopodia and lamellipodia while being incubated with 1.25 and 2.5 ppm AuNPs, indicating that the adhesion ability was enhanced by the nanoparticles. The expression of matrix metalloproteinase (MMP-2/9) in MSCs was found to be more highly expressed under 1.25 and 2.5 ppm AuNP treatment, relating to better cell migrating ability. Additionally, the cell apoptosis of MSCs investigated with Annexin-V/PI double staining assay and the Fluorescence Activated Cell Sorting (FACS) method demonstrated the lower population of apoptotic cells in 1.25 and 2.5 ppm AuNP treatments, as compared to high concentrations of AuNPs. Additionally, results from a Western blotting assay explored the possibility that the anti-apoptotic proteins Cyclin-D1 and Bcl-2 were remarkably expressed. Meanwhile, real-time PCR analysis demonstrated that the 1.25 and 2.5 ppm AuNP solutions induced a lower expression of inflammatory cytokines (TNF-α, IL-1β, IFN-γ, IL-6 and IL-8). According to the tests performed on an animal model, AuNP 1.25 and 2.5 ppm treatments exhibited the better biocompatibility performance, including anti-inflammation and endothelialization. In brief, 1.25 and 2.5 ppm of AuNP solution was verified to strengthen the biological functions of MSCs, and thus suggests that AuNPs become the biocompatibility nanomedicine for regeneration research.

Alzheimer's disease (AD) is a neurodegenerative disorder with an insidious onset and irreversible condition. Patients with mild cognitive impairment (MCI) are at high risk of converting to AD. Early diagnosis of unstable MCI patients is therefore vital for slowing the progression to AD. However, current diagnostic methods are either highly invasive or expensive, preventing their wide applications. Developing low-invasive and cost-efficient screening methods is desirable as the first-tier approach for identifying unstable MCI patients or excluding stable MCI patients. This study developed feature selection and machine learning algorithms to identify blood-sample gene biomarkers for predicting stable MCI patients. Two datasets obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were utilized to conclude 29 genes biomarkers (31 probes) for predicting stable MCI patients. A random forest-based classifier performed well with area under the receiver operating characteristic curve (AUC) values of 0.841 and 0.775 for cross-validation and test datasets, respectively. For patients with a prediction score greater than 0.9, an excellent concordance of 97% was obtained, showing the usefulness of the proposed method for identifying stable MCI patients. In the context of precision medicine, the proposed prediction model is expected to be useful for identifying stable MCI patients and providing medical doctors and patients with new first-tier diagnosis options.

Due to the characteristics of confusing varieties of Chinese medicinal materials, different sources, complex chemical composition, non-standard preparation process, and non-standard pharmaceutical equipment, the quality of Chinese medicinal preparations is difficult to be controlled and evaluated effectively under the current quality control mode and method of Chinese medicinal preparation. The present study proposed an engineering quality view of Chinese medicine pharmacy and a strategy to control the quality of Chinese medicinal preparations based on the current situation. The &quot;overall, dialectical, and dynamic&quot; multi-factor engineering quality view, covering original medicinal materials, preparation technologies, pharmaceutical equipment, and Chinese medicinal preparations, ensures the traceable process, measurable procedures, and feedback quality. The quality control mode of Chinese medicinal preparation with controllable sources, standardized preparation technologies, green pharmaceutical equipment, and intelligent manufacturing is built up.

Background: Cardiac surgery is associated with a substantial risk of major adverse events. Although carbon dioxide (CO 2 )-derived variables such as venous-to-arterial CO 2 difference (ΔPCO 2 ), and PCO 2 gap to arterial-venous O 2 content difference ratio (ΔPCO 2 /C (a-cv) O 2 ) have been successfully used to predict the prognosis of non-cardiac surgery, their prognostic value after cardiopulmonary bypass (CPB) remains controversial. This hospital-based study explored the relationship between ΔPCO 2 , ΔPCO 2 /C (a-cv) O 2 and organ dysfunction after CPB. Methods: We prospectively enrolled 114 intensive care unit patients after elective cardiac surgery with CPB. Patients were divided into the organ dysfunction group (OI) and non-organ dysfunction group (n-OI) depending on whether organ dysfunction occurred or not at 48 h after CPB. ΔPCO 2 was defined as the difference between central venous and arterial CO 2 partial pressure. Results: The OI group has 37 (32.5%) patients, 27 of which (23.7%) had one organ dysfunction and 10 (8.8%) had two or more organ dysfunctions. No statistical significance was found ( P = 0.84) for ΔPCO 2 in the n-OI group at intensive care unit (ICU) admission (9.0, 7.0-11.0 mmHg), and at 4 (9.0, 7.0-11.0 mmHg), 8 (9.0, 7.0-11.0 mmHg), and 12 h post admission (9.0, 7.0-11.0 mmHg). In the OI group, ΔPCO 2 also showed the same trend [ICU admission (9.0, 8.0-12.8 mmHg) and 4 (10.0, 7.0-11.0 mmHg), 8 (10.0, 8.5-12.5 mmHg), and 12 h post admission (9.0, 7.3-11.0 mmHg), P = 0.37]. No statistical difference was found for ΔPCO 2 /C (a-cv) O 2 in the n-OI group ( P = 0.46) and OI group ( P = 0.39). No difference was detected in ΔPCO 2 , ΔPCO 2 /C (a-cv) O 2 between groups during the first 12 h after admission ( P > 0.05). Subgroup analysis of the patients with two or more failing organs compared to the n-OI group showed that the predictive performance of lactate and Base excess (BE) improved, but not of ΔPCO 2 and ΔPCO 2 /C (a-cv) O 2 . Regression analysis showed that the BE at 8 h after admission (odds ratio = 1.37, 95%CI: 1.08-1.74, P = 0.009) was a risk factor for organ dysfunction 48 h after CBP. Conclusion : ΔPCO 2 and ΔPCO 2 /C (a-cv) O 2 cannot be used as reliable indicators to predict the occurrence of organ dysfunction at 48 h after CBP due to the pathophysiological process that occurs after CBP., 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 Zhang, Zheng, Chu, Jiang, Wang, Zhang, Qian, Yang, Zhang, Tung and Lin.)

Physical fitness (PF) is closely related to various health outcomes and quality of life among children. However, the associations between anthropometry, body composition (BC), and PF are not fully elucidated. This cross-sectional study aimed to investigate the associations between demographic metrics (age, sex), anthropometric measures (body mass index z-score (BMI z-score) waist/height ratio (WHtR)), BC parameters (body-fat percentage (BF%), muscle weight), and PF levels (800-m run, sit-and-reach, 1-min sit-ups, standing long jump) in school-aged children. Continuous variables were dichotomized by median splits. The results of 180 girls and 180 boys (mean age: 10.0 ± 0.7 years; mean BMI z-score: 0.366 ± 1.216) were analyzed. Multivariable linear regressions revealed that BF% (regression coefficient (B) = 3.4, 95% confidence interval (CI) = 2.5-4.3) was independently correlated with the 800-m run. Sex (B = 4.6, 95% CI = 3.0-6.3), age (B = 3.1, 95% CI = 1.9-4.3), and BMI z-score (B = -0.7, 95% CI = -1.4--0.1) were independently related to sit-and-reach. Age (B = 3.3, 95% CI = 2.0-4.7), BF% (B = -0.3, 95% CI = -0.4--0.2), and muscle weight (B = 0.7, 95% CI = 0.2-1.2) were independently associated with 1-min sit-ups. In addition to demography, anthropometry and BC provided additional information concerning some PF levels in school-aged children. Weight management and PF promotion should be addressed simultaneously in terms of preventive medicine and health promotion for children.

Over the past few years, the field of regulated cell death continues to expand and novel mechanisms that orchestrate multiple regulated cell death pathways are being unveiled. Meanwhile, researchers are focused on targeting these regulated pathways which are closely associated with various diseases for diagnosis, treatment, and prognosis. However, the complexity of the mechanisms and the difficulties of distinguishing among various regulated types of cell death make it harder to carry out the work and delay its progression. Here, we provide a systematic guideline for the fundamental detection and distinction of the major regulated cell death pathways following morphological, biochemical, and functional perspectives. Moreover, a comprehensive evaluation of different assay methods is critically reviewed, helping researchers to make a reliable selection from among the cell death assays. Also, we highlight the recent events that have demonstrated some novel regulated cell death processes, including newly reported biomarkers (e.g., non-coding RNA, exosomes, and proteins) and detection techniques., 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 Hu, Li, Lin, Shan, Yu, Wang, Liao, Yan, Wang, Shang, Huang, Zhang and Xiong.)

Aphis craccivora (Koch) is an economically important pest that affects legumes in worldwide. Chemical control is still the primary efficient method for A. craccivora management. However, the mechanism underlying insecticide resistance in A. craccivora has not been elucidated. A previous study observed that piperonyl butoxide (PBO) and diethyl maleate (DEM) significantly synergized imidacloprid in A. craccivora field populations, indicating that cytochrome P450 (P450) and glutathione S-transferase (GST) genes may play pivotal roles in imidacloprid resistance. In this study, 38 P450 genes and 10 GST genes were identified in A. craccivora through transcriptomic analysis. The expression levels of these P450 and GST genes were measured in susceptible (SUS) strains of A. craccivora under imidacloprid treatment with LC 15 , LC 50 , and LC 85 doses. The expression levels of CYP18A1 , CYP6CY21 , CYP6DA1 , CYP6DA2 , CYP4CJ1 , CYP4CJ2 , and CYP380C6 were up-regulated in the three treatments. Most of these genes belong to CYP3 and CYP4 Clans. In addition, the expression levels of all P450 and GST genes in A. craccivora were also measured in the Juye (JY) and Linqing (LQ) field populations. The expression levels of CYP6DA2 , CYP4CJ1 , and CYP380C6 were up-regulated in the SUS strain after imidacloprid treatment at three doses, and these genes were overexpressed in the JY population. Furthermore, the sensitivity of A. craccivora to imidacloprid was significantly increased after knockdown of CYP380C6 and CYP6DA2 through RNA interference. These results may help to elucidate the mechanisms underlying of imidacloprid resistance in A. craccivora ., 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 Yang, Lin, Li, Wang, Xue, Duan, Zhao and Zhang.)

Objective: Pediatric lumbar disc herniation (LDH), although uncommon, causes significant pain, discomfort, and sometimes disability. We examined the efficacy of percutaneous endoscopic lumbar discectomy (PELD) for pediatric LDH and the degree of lumbar disc degeneration at 1 year after PELD., Methods: We retrospectively reviewed the data of pediatric patients with LDH who underwent PELD from December 2007 to July 2018. The patients' symptoms, physical examination findings, clinical images, visual analog scale (VAS) scores, Oswestry Disability Index (ODI), and perioperative results (blood loss, length of hospital stay, and complications) were obtained from the medical records. Lumbar disc degeneration was graded using the modified Pfirrmann grading system at the 1-year postoperative magnetic resonance imaging (MRI) examination., Results: Six boys and four girls who underwent PELD were evaluated. The patients' mean age was 15.6 years (range, 13-17 years). The mean VAS score for low back pain, mean VAS score for lower limb pain, and mean ODI preoperatively and 1 year postoperatively were 6.2 and 0.3, 6.9 and 0.5, and 20 and 0.1, respectively. MRI showed significant disc degeneration after PELD., Conclusions: Treating pediatric LDH with PELD is safe and effective. It relieves pain and reduces disability. However, lumbar disc degeneration still occurs.

This cross-sectional study aimed to investigate the associations between high-sensitivity C-reactive protein (hs-CRP) and renal impairment (RI) among middle-aged and elderly people. We collected and analyzed demographic, anthropometric, metabolic, and renal function data in a community-based population in Northern Taiwan. We excluded subjects with acute inflammation from this study and defined RI as the presence of urinary albumin-creatinine ratio 30-300 mg/g or an estimated glomerular filtration rate of <60 mL/min/1.73 m 2 . There were 131, 125, and 125 participants in the low (≤0.80 mg/L), middle (0.81-1.76 mg/L), and high (>1.77 mg/L) hs-CRP tertiles, respectively. hs-CRP exhibited significantly positive correlations with body mass index, waist circumference, systolic blood pressure, triglyceride, and fasting plasma glucose, and a negative correlation with high-density lipoprotein. The prevalence and odds ratio of RI significantly increased across hs-CRP tertiles from low to high, and this trend remained significant after adjusting for the conventional cardiometabolic risk factors. hs-CRP ≥ 1.61 mg/L in the total group and ≥2.03 mg/L in the elderly group accurately predicted RI ( p = 0.01 and 0.03, respectively). These findings suggest that we should carefully evaluate the renal function for at-risk individuals with hs-CRP elevation.

Body composition (BC) parameters are associated with cardiometabolic diseases in children; however, the importance of BC parameters for predicting pediatric hypertension is inconclusive. This cross-sectional study aimed to compare the difference in predictive values of BC parameters and conventional anthropometric measures for pediatric hypertension in school-aged children. A total of 340 children (177 girls and 163 boys) with a mean age of 8.8 ± 1.7 years and mean body mass index (BMI) z-score of 0.50 ± 1.24 were enrolled (102 hypertensive children and 238 normotensive children). Significantly higher values of anthropometric measures (BMI, BMI z-score, BMI percentile, waist-to-height ratio) and BC parameters (body-fat percentage, muscle weight, fat mass, fat-free mass) were observed among the hypertensive subgroup compared to their normotensive counterparts. A prediction model combining fat mass ≥ 3.65 kg and fat-free mass ≥ 34.65 kg (area under the receiver operating characteristic curve = 0.688; sensitivity = 66.7%; specificity = 89.9%) performed better than BMI alone (area under the receiver operating characteristic curve = 0.649; sensitivity = 55.9%; specificity = 73.9%) in predicting hypertension. In conclusion, BC parameters are better than anthropometric measures in predicting pediatric hypertension. BC measuring is a reasonable approach for risk stratification in pediatric hypertension.

Objectives: Host immune responses are indispensable to combat the disease. We report the dynamics of peripheral immune cells, cytokines, and human leucocyte antigen-G (HLA-G) and its receptor expressions in a patient suffering from critical COVID-19 pneumonia to convalescence., Methods: Clinical data of the patient were collected from medical records. The expressions of HLA-G and receptors ILT2, ILT4 and KIR2DL4 in peripheral immune cells were measured with flow cytometry., Results: From critical COVID-19 to the convalescent stage, early lymphopenia was improved (median: 0.6 × 10 9  L -1 vs. 0.9 × 10 9  L -1 , P  = 0.009), and an obvious fluctuation in WBC and neutrophil counts was observed. Initially, low levels of CD4 + T cells (from 120 to 528 μL -1 ) and CD8 + T cells (from 68 to 362 μL -1 ) gradually increased to normal levels. Meanwhile, high IL-6 (from 251.8 to 6.32 pg mL -1 ), IL-10 (from 39.53 to 5.21 pg mL -1 ) and IFN-γ (from 13.55 to 3.16 pg mL -1 ) levels decreased, and IL-4 (from 2.36 to 3.19 pg mL -1 ) and TNF-α (from 2.27 to 20.2 pg mL -1 ) levels increased quickly when the viral RNA returned negative. Moreover, the percentage of HLA-G + T cells, B cells and monocytes follows high-low-high pattern, while the percentage of receptors ILT2-, ILT4- and KIR2DL4-expressing cells remained relatively stable., Conclusion: Our findings provide valuable information on the dynamics of early peripheral immunological responses in SARS-CoV-2 infection. CD4 + and CD8 + T cells, cytokines and HLA-G + immune cells are associated with the natural history of the critical COVID-19 patient; however, future studies are necessary., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology Inc.)

Background: Clinically significant bifurcation lesions account for up to 20% of percutaneous coronary intervention (PCI) procedures, and present technical challenges due to the potential for occlusion of the side branch vessel. Percutaneous coronary intervention using final kissing ballooning (FKB) plays a major role in treating bifurcation lesions, but sequential dilatation (SD) is a less complicated PCI technique with a shallower learning curve. Previous studies have shown no benefit of FKB over SD, but wide-angle (>70°) bifurcation lesions may respond differently to narrow-angle bifurcation lesions., Methods: Retrospective analysis was carried out to compare outcomes of FKB and SD stenting specifically for wide-angle bifurcation lesions: 7,582 PCIs performed at a single medical centre between 1 January 2009 and 31 May 2016 were screened. This yielded 112 SD and 102 FKB cases for comparative analysis, which was conducted with respect to major adverse cardiac event (MACE)-free survival and target lesion revascularisation (TLR)-free survival rates., Results: The comparative analysis was achieved using the log-rank test and presented as Kaplan-Meier curves. All baseline characteristics were balanced among the groups. The mean procedure and fluoroscopy times were significantly longer for patients with FKB than SD. Patients with SD had slightly better MACE and TLR rates than those with FKB in both the drug-eluting stent (DES) and bare metal stent (BMS) groups. In addition, patients with DES had slightly lower MACE and TLR rates than those with BMS in both the FKD and SD groups. Major adverse cardiac event-free survival and TLR-free survival rates were also slightly higher in patients with DES than those with BMS in both the FKD and SD groups. However, these differences were not statistically significant., Conclusions: These results suggest that the most applicable procedure for PCI of wide-angulated bifurcation stenosis would be a combination of DES and SD., (Copyright © 2019. Published by Elsevier B.V.)

Hyperglycemia plays crucial roles in vascular disease development, including macrovascular and microvascular diseases from diabetes mellitus (DM). Our previous study demonstrated that Ruellia tuberosa L. (RTL) aqueous and ethanol extracts alleviate hyperglycemia and inhibit insulin resistance in diabetic rats. This study investigated the protective effect of RTL ethanol extract against aorta dysfunction in high-fat diet (HFD) and streptozotocin (STZ)-induced type 2 DM (T2DM) rats. Results showed that RTL ethanol extract (100 and 400 mg/kg BW/day) ameliorated serum lipid profiles, including triglyceride, free fatty acid, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels. It also significantly reduced the level of serum cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 in T2DM rats. Additionally, RTL extract decreased endothelin-1 and endothelial nitric oxide contents, reduced the level of cell adhesion factors, including monocyte chemoattractant protein-1 and cell adhesion factor vascular cell adhesion molecule-1, while decreasing content of damage factors, namely tissue factor and von Willebrand factor in aortic tissues of diabetic rats. Equally noteworthy is that RTL extract enhanced the activity of aorta antioxidative enzymes, including superoxidase dismutase and catalase in diabetic rats, suggesting that RTL ethanol extract may ameliorate aorta dysfunction via enhancing aortic antioxidative enzyme activity, which subsequently suppresses aorta endothelial damage-associated factors in HFD with STZ-induced T2DM rats., Competing Interests: The authors declare that they do not have any conflict of interest., (© 2019 The Authors. Food Science & Nutrition published by Wiley Periodicals, Inc.)

Childhood obesity has been shown to be closely related to future obesity and comorbidities. As its prevalence and impact has increased significantly worldwide, researchers have focused on prevention and intervention. This study assessed a multifaceted intervention for elementary school children.A retrospective data collection with a cohort analysis was employed. A 16-week school-based intervention with nutritional intervention, physical activity, and behavioral education was designed and conducted by a multidisciplinary team for 1860 children aged 6 to 13 years. Basic information, anthropometrics, and physical fitness (PF) were recorded before and after the intervention. The differences compared with a reference group, and compared between subgroups, were analyzed.Significant favorable changes in body weight and composition were found. Children's height, weight, and muscle weight increased, whereas BMI, BMI z-score (zBMI), waist circumference, hip circumference, waist-hip ratio, waist-height ratio, body fat percentage, and visceral fat area decreased. Sit-ups and 800-m run time significantly improved. Girls exhibited a greater reduction in body weight outcomes; boys improved more in body composition and PF. Students with higher zBMI had a greater reduction in all anthropometrics; students with lower zBMI showed greater PF improvement, except for the 800-m run.The intervention improved weight measures, body composition, and PF. Subgroup differences suggested the need for sex- and weight-specific interventions.

Purpose: The expression level of platelet microRNAs (miRNAs) correlates with heart disease and may be altered by antiplatelet therapy. This study aims to assess whether certain miRNAs are associated with treatment response by platelets in patients who received percutaneous coronary intervention and antiplatelet therapy. The dynamic expression of certain miRNAs in patients receiving different antiplatelet regimens was also investigated., Methods: Healthy subjects (N = 20) received no-stent or antiplatelet therapy (as control), and patients (N = 155) who underwent stent implant and received treatment regimens that included aspirin plus clopidogrel, ticagrelor, or cilostazol were included. The association of miR-96-5p, miR-495-3p, miR-107, miR-223-3p, miR-15a-5, miR-365-3p, and miR-339-3p levels with treatment response, SYNTAX score, and HTPR was determined., Results: Of the different treatment regimens, ticagrelor was the most efficacious. At 24 h following drug administration, ROC analysis revealed that miR-339-3p and miR-365-3p had the highest sensitivity (74.3% and 90.0%, respectively) and specificity (71.4% and 93.3%) for detecting HTPR compared with the five other miRNAs. The SYNTAX score positively correlated with miR-223-3p and miR-365-3p levels at 24 h (P ≤ 0.006) and with miR-365-3p levels 7 days following drug administration (P = 0.014). The expression of all three miRNAs reached the highest levels in hyperresponsive (P2Y12 reaction unit < 85) followed by hyporesponsive (P2Y12 reaction unit ≥ 208) and then normoreactive. The normoreactive value was very close to that of controls., Conclusions: Our data suggest that miR-365-3p expression level correlates with the antiplatelet treatment response., Clinical Trial Registration: NCT02101437.

Purpose: Current treatment guidelines do not recommend different antiplatelet treatments for patients in different coronary risk categories; nor do they consider ethnic differences in responses to individual drugs., Objectives: We performed a prospective, single-blind, randomized, comparative study of Taiwanese patients with stable angina and scheduled stent implantation for intermediate-to-highly complex coronary lesions and compared the platelet reactivity unit (PRU) levels and 24-month outcomes of groups receiving three different antiplatelet treatments., Methods: Patients (N = 334) were randomized into three treatment groups (aspirin + clopidogrel, aspirin + ticagrelor, or aspirin + clopidogrel + cilostazol) for 6 months of treatment and were then switched to aspirin only. PRU levels were determined 24 h, 7 days, and 1 month after stent implantation. Clinical outcomes and adverse events were recorded over 24 months., Results: Clopidogrel treatment reached full effect after 1 month. Ticagrelor decreased PRU levels more than did clopidogrel but often to levels that increased the risk of hemorrhage. The addition of cilostazol to clopidogrel decreased PRU levels earlier and more strongly than clopidogrel alone but not as strongly as did ticagrelor. Ticagrelor treatment caused fewer major adverse cardiovascular events (MACEs) and more episodes of minor bleeding than the other two treatments., Conclusions: Clopidogrel appears safer than ticagrelor in Taiwanese patients with stable angina after stent implantation for intermediate-to-highly complex coronary lesions. The addition of cilostazol to clopidogrel may provide a more rapid decrease in PRU to therapeutic levels without increasing the risk of hemorrhage., Clinical Trial Registration Number: NCT02101411.

Background: Marinating meat with alcohol, such as wine and beer, is a common culinary practice in cultures worldwide. In this study we use a model marination solution comprising 0.2  mol L -1 glucose-0.2  mol L -1 glycine buffered to pH 4.3 containing either 0 or 50% ethanol and mimicked the cooking process by heating for 12 h. Antioxidative and antimutagenic characteristics of Maillard reaction products (MRPs) were investigated. Reducing power, antioxidant activity (ferrous ion chelating ability), and free radical neutralization ability generated from 1,1-diphenyl-2-pichrylhydrazyl and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) were determined. Ames testing was performed., Results: Results indicate that MRPs from aqueous and alcoholic solution exhibit four antioxidative assays in a dose-dependent manner from 0.16 to 10.00 mg mL -1 . However, MRPs from the alcoholic model were superior. In Ames testing, MRPs from both models are neither toxic nor mutagenic at the test concentrations of 0.63-10.00 mg/plate. However, MRPs from the alcoholic model exhibited a higher inhibitory effect on the direct-acting mutagen 4-nitroquinoline-N-oxide compared with the aqueous model. This result is consistent with the observation that MRPs with higher antioxidative capacity exhibit superior antimutagenic activity, suggesting that there are more different products in the alcoholic model., Conclusion: Our results add to the current knowledge about the antioxidative and antimutagenic properties of MRPs arising when food is cooked in the presence of ethanol. © 2018 Society of Chemical Industry., (© 2018 Society of Chemical Industry.)

Ruellia tuberosa L. (RTL) exhibits a wide range of phytochemical activities, for example, on treatment of diabetes mellitus (DM), in Orient. There is, however, few study regarding the effect of RTL on glycemic-related homeostasis in type 2 DM (T2DM). We investigated the effect of RTL aqueous and ethanolic extracts on hypoglycemia in high-fat diet (HFD)-fed plus streptozotocin (STZ)-induced T2DM rats, and examined the effect of RTL on glucose uptake in tumor necrosis factor-α-induced insulin-resistant mouse C2C12 myoblasts, a mouse skeletal muscle cell line. The administration of 100 or 400 mg kg BW -1  day -1 of RTL aqueous or ethanolic extracts once a day for 4 weeks significantly ameliorated hyperglycemia, hyperinsulinemia, and the insulin resistance (IR) index in diabetic rats. RTL either aqueous or ethanolic extract at a concentration of 25-800 μg/ml significantly improved glucose uptake in insulin-resistant mouse C2C12 myoblasts, indicating inhibiting the IR in skeletal muscles. These evidences suggest that RTL ameliorates hyperglycemia in HFD/STZ-induced T2DM rats may be attributed to the alleviation of IR in skeletal muscles.

Background: Nanotechnology is emerging as a promising tool to perform noninvasive therapy and optical imaging. However, nanomedicine may pose a potential risk of toxicity during in vivo applications. In this study, we aimed to investigate the potential toxicity of rare-earth nanoparticles (RENPs) using mice as models., Methods: We synthesized RENPs through a typical co-precipitation method. Institute of Cancer Research (ICR) mice were randomly divided into seven groups including a control group and six experimental groups (10 mice per group). ICR mice were intravenously injected with bare RENPs at a daily dose of 0, 0.5, 1.0, and 1.5 mg/kg for 7 days. To evaluate the toxicity of these nanoparticles in mice, magnetic resonance imaging (MRI) was performed to assess their uptake in mice. In addition, hematological and biochemical analyses were conducted to evaluate any impairment in the organ functions of ICR mice. The analysis of variance (ANOVA) followed by a one-way ANOVA test was used in this study. A repeated measures' analysis was used to determine any significant differences in white blood cell (WBC), alanine aminotransferase (ALT), and creatinine (CREA) levels at different evaluation times in each group., Results: We demonstrated the successful synthesis of two different sizes (10 nm and 100 nm) of RENPs. Their physical properties were characterized by transmission electron microscopy and a 980 nm laser diode. Results of MRI study revealed the distribution and circulation of the RENPs in the liver. In addition, the hematological analysis found an increase of WBCs to (8.69 ± 0.85) × 10 9 /L at the 28 th day, which is indicative of inflammation in the mouse treated with 1.5 mg/kg NaYbF 4 :Er nanoparticles. Furthermore, the biochemical analysis indicated increased levels of ALT ([64.20 ± 15.50] U/L) and CREA ([27.80 ± 3.56] μmol/L) at the 28 th day, particularly those injected with 1.5 mg/kg NaYbF 4 :Er nanoparticles. These results suggested the physiological and pathological damage caused by these nanoparticles to the organs and tissues of mice, especially to liver and kidney., Conclusion: The use of bare RENPs may cause possible hepatotoxicity and nephritictoxicity in mice., Competing Interests: There are no conflicts of interest

X-ray luminescence optical imaging has been recognized as a powerful technique for medical diagnosis due to its deep penetration and low auto-fluorescence in tissues. However, the low luminescence efficiency of current X-ray luminescence nanoprobes remains a major hurdle for sensitive bioimaging in practical medical applications. Here we present a new kind of energy transfer-sensitized X-ray luminescence nanoprobe (PEG-NaGd(WO 4 ) 2 :Eu) for highly effective optical bioimaging. Under X-ray excitation, the tungstate host absorbs the X-ray photons and then transfers the energy to the Eu 3+ luminescence center, thus enhancing the luminescence efficiency of the nanoprobes for high sensitivity optical in vivo imaging. Moreover, the shortened T 1 relaxation response of Gd 3+ ions and X-ray attenuation capability of W atoms enable the nanoprobes to serve as efficient contrast agents for magnetic resonance imaging (MRI) and computed tomography (CT) imaging. Therefore, combined with the MRI, CT and X-ray luminescence imaging capabilities, the present PEG-NaGd(WO 4 ) 2 :Eu nanoprobes could be used as promising multimodal imaging contrast agents in biological systems.

Background: Luminescent rare-earth-based nanoparticles have been increasingly used in nanomedicine due to their excellent physicochemical properties, such as biomedical imaging agents, drug carriers, and biomarkers. However, biological safety of the rare-earth-based nanomedicine is of great significance for future development in practical applications. In particular, biological effects of rare-earth nanoparticles on human's central nervous system are still unclear. This study aimed to investigate the potential toxicity of rare-earth nanoparticles in nervous system function in the case of continuous exposure., Methods: Adult ICR mice were randomly divided into seven groups, including control group (receiving 0.9% normal saline) and six experimental groups (10 mice in each group). Luminescent rare-earth-based nanoparticles were synthesized by a reported co-precipitation method. Two different sizes of the nanoparticles were obtained, and then exposed to ICR mice through caudal vein injection at 0.5, 1.0, and 1.5 mg/kg body weight in each day for 7 days. Next, a Morris water maze test was employed to evaluate impaired behaviors of their spatial recognition memory. Finally, histopathological examination was implemented to study how the nanoparticles can affect the brain tissue of the ICR mice., Results: Two different sizes of rare-earth nanoparticles have been successfully obtained, and their physical properties including luminescence spectra and nanoparticle sizes have been characterized. In these experiments, the rare-earth nanoparticles were taken up in the mouse liver using the magnetic resonance imaging characterization. Most importantly, the experimental results of the Morris water maze tests and histopathological analysis clearly showed that rare-earth nanoparticles could induce toxicity on mouse brain and impair the behaviors of spatial recognition memory. Finally, the mechanism of adenosine triphosphate quenching by the rare-earth nanoparticles was provided to illustrate the toxicity on the mouse brain., Conclusions: This study suggested that long-term exposure of high-dose bare rare-earth nanoparticles caused an obvious damage on the spatial recognition memory in the mice.

Objectives: Hearing deterioration is a major concern for hearing-preserved patients with vestibular schwannomas who are treated with stereotactic radiosurgery (SRS). Thus, determining which patients are more likely to have worse hearing outcomes following SRS may facilitate clinicians in deciding whether conservative policy should be applied in the interest of hearing preservation. This study aimed to define the predictors of hearing outcomes following SRS., Patients and Methods: This retrospective study included 100 patients who underwent low-dose SRS (12- to 13-Gy marginal dose) for vestibular schwannomas between January 2004 and January 2014. Clinical factors and hearing outcomes following radiosurgery were reviewed., Results: All patients had serviceable hearing at diagnosis and prior to SRS. The median follow-up period was 6.5years (range, 3-10years). The hearing preservation rate in the first, third, and fifth year after radiosurgery was 89%, 68%, and 63%, respectively. A mean cochlear dose lower than 4Gy was a favorable predictor of hearing outcome. Maximal cochlear dose, patient age, pre-treatment pure-tone average, and imaging characteristics were not associated with post-treatment hearing preservation. Our study showed an accelerated rate of deterioration of serial pure-tone average in the first 3years, followed by a more gradual decline after radiosurgery., Conclusion: Our results suggest that cochlear dose constraint is the most crucial factor for hearing preservation. This study provides insight into the rate of hearing preservation and the pattern of hearing deterioration following radiosurgery and can help clinicians advise patients of hearing outcomes following SRS., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To investigate the feasibility of utilizing the current acute gastrointestinal injury(AGI) grading system, and explore the association of severity of AGI grade with clinical outcome in critically ill patients. Methods: The adult patients from 14 general ICUs in Zhejiang Province with an expected admission to ICU for at least 24 h were recruited, and all clinical, laboratory, and survival data were prospectively collected. The AGI grade was daily assessed based on GIsymptoms, feeding details and organ dysfunctionon the first week of admission to ICU.The intra-abdominal pressures(IAP) was measured using AbViser device. Results: Of 550 patients enrolled, mean values for age and APACHE Ⅱ score were (64.9±17.2) years and (19.5±7.4), respectively. 456 patients(82.9%) took mechanical ventilation, and 470 patients were identified for AGI. The distribution of AGI grade on the frist day of ICU admission were 50.6%(Ⅰ grade, n =238), 34.2%(Ⅱ grade, n =161), 12.4%(Ⅲ grade, n =58) and 2.8%(Ⅳ, n =13), respectively, while the distribution of the global AGI grade based on the 7-day AGI assessment of ICU admission were 24.5%(Ⅰ grade, n =115), 49.4%(Ⅱ grade, n =232), 20.6%(Ⅲ grade, n =97) and 5.5%(Ⅳ, n =26), respectively. 28- and 60-day mortality rate was 29.3%( n =161) and 32.5%( n =179), respectively. The patients with AGI had a higher 28-(31.1% vs 18.8%, P =0.025) and 60-day survival rate(34.7% vs 20.0%, P =0.01) than those with non-AGI, and also there were positive correlations between AGI grade and 28- and 60-day mortality( P <0.001). Univariate Cox regression analysis showed that age, the source of medicial admission, diabetes mellitus, coronary heart disease, the use of vasoactive drugs, serum creatinine and lactate, mechanical ventilation, APACHE Ⅱ score, the AGI grade in the first day of ICU admission and feeding intolerance within the first week of ICU stay were significantly( P ≤0.02) associated with mortality. In multivariate analysis including all these variables, the source of medical admission(χ(2)=4.34, P =0.04), diabete mellitus(χ(2)=3.96, P =0.05), the use of vasoactive drugs(χ(2)=6.55, P =0.01), serum lactate(χ(2)=4.73, P =0.03), the global AGI grade in the 7-day of ICU admission(χ(2)=7.10, P =0.008), and APACHE Ⅱ score(χ(2)=12.1, P <0.001) remained independent predictors for 60-day mortality.In the further subgroup analysis including 402 patients with 7-day survival, the feeding intolerance within the first week of ICU stay could provide independent and incremental prognostic value of 60-day mortality wtih increased χ(2)value of Cox regression model(χ(2)=52.2 vs 41.9, P =0.007) . Conclusion: The AGI grading system is useful for identifying the severity of gastrointestinal dysfunction, and could be used as a strong predictor of impaired outcome. The results provide evidence to support that feeding intolerance within 7 days of admission to ICU was an independent determinant of mortality.

Background: The haemoflagellate Trypanosoma lewisi is a kinetoplastid parasite which, as it has been recently reported to cause human disease, deserves increased attention. Characteristic features of all kinetoplastid flagellates are a uniquely structured mitochondrial DNA or kinetoplast, comprised of a network of catenated DNA circles, and RNA editing of mitochondrial transcripts. The aim of this study was to describe the kinetoplast DNA of T. lewisi., Methods/results: In this study, purified kinetoplast DNA from T. lewisi was sequenced using high-throughput sequencing in combination with sequencing of PCR amplicons. This allowed the assembly of the T. lewisi kinetoplast maxicircle DNA, which is a homologue of the mitochondrial genome in other eukaryotes. The assembly of 23,745 bp comprises the non-coding and coding regions. Comparative analysis of the maxicircle sequence of T. lewisi with Trypanosoma cruzi, Trypanosoma rangeli, Trypanosoma brucei and Leishmania tarentolae revealed that it shares 78%, 77%, 74% and 66% sequence identity with these parasites, respectively. The high GC content in at least 9 maxicircle genes of T. lewisi (ATPase6; NADH dehydrogenase subunits ND3, ND7, ND8 and ND9; G-rich regions GR3 and GR4; cytochrome oxidase subunit COIII and ribosomal protein RPS12) implies that their products may be extensively edited. A detailed analysis of the non-coding region revealed that it contains numerous repeat motifs and palindromes., Conclusions: We have sequenced and comprehensively annotated the kinetoplast maxicircle of T. lewisi. Our analysis reveals that T. lewisi is closely related to T. cruzi and T. brucei, and may share similar RNA editing patterns with them rather than with L. tarentolae. These findings provide novel insight into the biological features of this emerging human pathogen.

Mol Med rep 12: [Related article:] 1321–1327, 2015; DOI: 10.3892/m mr.2015.3511 After the publication of the article, the authors noted that they had made an error regarding the spelling of Gualou Guizhi in their manuscript. In the title and on page 1 line 59, Guolou Guizhi should be replaced with Gualou Guizhi.

The aim of the present study was to explore the neuroprotective effects of Gualou Guizhi decoction (GLGZD) in a rat model of middle cerebral artery occlusion (MCAO). Sprague-Dawley rats were divided into three groups: Sham (no MCAO), MCAO (MCAO with no GLGZD treatment) and GLGZD (MCAO with GLGZD treatment). Rats in the MCAO and GLGZD groups were subjected to permanent occlusion of the left middle cerebral artery. Neurological function and infarct volume were measured. Microglial activation and inflammatory cell accumulation were measured using immunohistochemistry. mRNA and protein expression of inflammatory mediators were examined using reverse transcription-quantitative polymerase chain reaction and an enzyme-linked immunosorbent assay. The expression of proteins associated with the nuclear factor κ-B (NF-κB) inflammation signaling pathway was analyzed using western blotting. The results of the present study suggested that infarct size was significantly reduced and neurological behavior function was improved in rats with MCAO treated with GLGZD compared with rats in the MCAO group. Amoeboid microglial expansion and inflammatory cell migration were observed in the infarcted areas of rats in the GLGZD group and were not identified in those of the MCAO group. Target mRNA and protein levels, and inflammatory cell infiltration were significantly reduced in the GLGZD group compared with the MCAO model group. Notably, GLGZD treatment induced neuroprotective effects, reducing inflammation and inhibiting NF-κB signaling compared with the MCAO group. Therefore, GLGZD may exhibit anti-inflammatory effects against ischemia-reperfusion brain injury and may be a therapeutic target for ischemic stroke.

Hallux valgus (HV) related pain and disability remains a medical challenge to date. We have evaluated the therapeutic effect of intramuscular Botulinum Toxin type A (BTX-A) injection on painful HV in a double-blind randomized controlled trial. Sixteen patients having painful HV in at least one foot from the Department of Physical Medicine and Rehabilitation at a medical center in northern Taiwan have participated. Patients were randomized into two groups to receive intramuscular injections of either BTX-A or normal saline (NS) to the oblique and transverse heads of the adductor hallucis, flexor hallucis brevis and extensor hallucis longus muscles. Primary outcome measurements were selected from the Taiwan Chinese version of the Foot Function Index subscales on pain (questions 1-6, 9) and disability (question 10-18). The secondary outcome measurement was the HV angle. Patients were assessed at baseline and at 1, 2, 3, and 6 months after treatment. The demographic data and measurements were comparable between the two groups at baseline (p>0.05). BTX-A and NS reduced pain and disability one month after injection. Pain reduction induced by BTX-A injection lasted for at least 6 months while that induced by NS lasted for only 1 month. In addition, patients in the BTX-A group showed greater improvement in pain score (p<0.001), disability score (p<0.05), and HV angle (p<0.05) than patients in the NS group. The results reflected that HV-related muscle injection of BTX-A resulted in a marked reduction in pain for up to 6 months., (© 2015 Elsevier B.V. All rights reserved.)

Background: This study reviews our recent experience with deep neck infections in order to propose recommendations in selecting presumptive antibiotics according to imaging characteristics and identifying predisposing factors of life-threatening complications., Methods: The records of 161 patients treated for deep neck infections at the Department of Otolaryngology-Head and Neck Surgery, China Medical University Hospital from 2002 to 2012 were reviewed retrospectively. The demographic data, comorbidities, source of infections, complications, duration of hospital stay, imaging characteristics, and bacteriologic studies were evaluated. The involved neck space was determined by computed tomography (CT) scan with contrast. Complications included mortality and life-threatening conditions., Results: The most common cause of deep neck infections in our study was odontogenic infection (20.5%), followed by pharyngo-tonsillitis (18.6%), and lymphadenitis (10.5%). The most commonly involved neck space was the submandibular space (40.9%), followed by the carotid space (37.2%), and the para-pharyngeal space (33.5%). Gas formation was detected in 31 (19.3%) cases. Infections of the different neck spaces and patients with gas formation noted on CT scan showed a specific distribution of common microorganisms. Streptococcus spp. was the most common pathogen in submandibular/sublingual space infections. Klebsiella pneumoniae infection accounted for 53.1% of peri-tonsillar/para-pharyngeal space infections, and 40% of carotid space infections. When gas formation was noted on CT imaging, anaerobic infection was the most common pathogen. Chronic kidney disease, diabetes mellitus (DM), multiple space infection, and gas formation present on CT scan were independent predictors of complications (p<0.05)., Conclusion: The imaging characteristics and microbiology of patients with deep neck infections are correlated and can facilitate the optimal selection of antibiotics. We can administer more precise presumptive antibiotics according to the identified involved neck space on CT scan. Patients with predisposing factors of life-threatening complications require early aggressive multi-disciplinary management to prevent severe sequelae.

Diagnosis of coronary artery disease requires invasive procedures that are typically not implemented until clinical warning signs are apparent. The goal of this study was to determine the relation between the severity of coronary artery disease, as measured by the SYNTAX scoring system, with serum levels of fetuin-A and fibroblast growth factor 23 (FGF23) in the general population. We enrolled 165 patients who had stable angina and positive results on treadmill testing or abnormal results on thallium myocardial perfusion scanning showing perfusion defects or who had acute coronary syndromes. Patients were hospitalized for evaluation with angiography, with or without simultaneous percutaneous coronary intervention. SYNTAX Scores were calculated on the basis of the results of coronary angiography using a computer-based questionnaire of sequential and interactive self-guided questions. Univariate analysis was used to assess the significance of fetuin-A and FGF23, as well as gender, age, body mass index, waist circumference, diabetes, hypertension, creatinine, total cholesterol, cholesterol, triglycerides, and high-sensitivity C-reactive protein in relation to cardiovascular disease severity. Multivariate analysis with stepwise regression was used to assess the utility of fetuin-A and FGF23 as predictors of SYNTAX Score. Multivariate analysis showed log fetuin-A to be a significant predictor of SYNTAX Score (p <0.0001) after controlling for the significant factors gender, cholesterol levels, and log high-sensitivity C-reactive protein. Log FGF23 values were also shown by multivariate regression to significantly predict SYNTAX Score (p = 0.0137) after controlling for gender, creatinine, cholesterol, and log high-sensitivity C-reactive protein. In conclusion, fetuin-A and FGF23 can be considered in combination with noninvasive test results as patient selection criteria for performing angiography., (Copyright © 2013 Elsevier Inc. All rights reserved.)

We study the cytotoxicity of indium chloride (InCl₃) in Chinese hamster lung fibroblasts, the V79 cells, using MTT assay. The results showed that InCl₃ did not induce significant cytotoxicity at various concentrations tested. In addition, the frequency of micronuclei (MN) was assayed to evaluate the genotoxic effects of InCl₃ in V79 cells. InCl₃ at concentrations ranged 0.1-1 μM significantly increased MN frequency in a concentration-dependent manner. Both catalase and superoxide dismutase at concentrations of 75 and 150 μg/mL significantly inhibited InCl₃-induced MN. Similarly, Germanium oxide (GeO₂) and dimercaprol expressed antigenotoxic effects. From these findings, it is concluded that InCl₃ is a potent genotoxic chemical, which may be mediated partly by inducing oxidative stress. The significance of this study shows that the workers in the semiconductor factories should be cautious in exposing to the hazardous genotoxic InCl₃., (Copyright © 2011 Wiley Periodicals, Inc., a Wiley company.)

Chinese hamster ovary (CHO) cells, its lung fibroblasts (V79), and human lymphocytes are routinely used in in vitro cytogenetic assays, which include micronuclei (MN), sister chromatid exchange (SCE), and chromosome aberration (CA) assays. Mitomycin C (MMC), a DNA cross-link alkylating agent, is both an anticancer medicine and a carcinogen. To study the differential representative values of cell types in MMC-treated cytogenetic assays and its upstream factor, cysteine aspartic acid-specific protease (caspase)-3. Among the chosen cell types, lymphocytes expressed the highest sensitivity in all three MMC-induced assays, whereas CHO and V79 showed varied sensitivity in different assays. In MN assay, the sensitivity of CHO is higher than or equal to V79; in SCE assay, the sensitivity of CHO is the same as V79; and in CA assay, the sensitivity of CHO is higher than V79. In-depth analysis of CA revealed that in chromatid breaks and dicentrics formation, lymphocyte was the most sensitive of all and CHO was more sensitive than V79; and in acentrics and interchanges formation, lymphocyte was much more sensitive than the others. Furthermore, we found caspase-3 activity plays an important role in MMC-induced cytogenetic assays, with MMC-induced caspase-3 activity resulting in more sensitivity in lymphocytes than in CHO and V79. Based on these findings, lymphocyte will make a suitable predictive or representative control reference in cytogenetic assays and caspase-3 activity with its high specificity, positive predictive value, and sensitivity.

In a chemical screening, we tested the antiangiogenic effects of fumagillin derivatives and identified fumagillin as an inhibitor of definitive hematopoiesis in zebrafish embryos. Fumagillin is known to target methionine aminopeptidase II (MetAP2), an enzyme whose function in hematopoiesis is unknown. We investigated the role of MetAP2 in hematopoiesis by using zebrafish embryo and human umbilical cord blood models. Zebrafish metap2 was expressed ubiquitously during early embryogenesis and later in the somitic region, the caudal hematopoietic tissue, and pronephric duct. metap2 was inhibited by morpholino and fumagillin treatment, resulting in increased mpo expression at 18 hours postfertilization and reduced c-myb expression along the ventral wall of dorsal aorta at 36 hours postfertilization. It also disrupted intersegmental vessels in Tg(fli1:gfp) embryos without affecting development of major axial vasculatures. Inhibition of MetAP2 in CB CD34(+) cells by fumagillin had no effect on overall clonogenic activity but significantly reduced their engraftment into immunodeficient nonobese diabetes/severe combined immunodeficiency mice. metap2 knock-down in zebrafish and inhibition by fumagillin in zebrafish and human CB CD34(+) cells inhibited Calmodulin Kinase II activity and induced ERK phosphorylation. This study demonstrated a hitherto-undescribed role of MetAP2 in definitive hematopoiesis and a possible link to noncanonical Wnt and ERK signaling.

Acute lung injury (ALI) in critically ill patients remains the leading cause of mortality and morbidity. Lipopolysaccharide (LPS) is a key mediator of lung injury. This study investigates the protective effects and mechanisms of luteolin in intratracheal instillation of LPS (100μg)-induced ALI in mice. Pretreatment of mice with 70μmol/kg luteolin significantly restores LPS-induced decrease in oxygen pressure and increase in carbon dioxide in arterial blood. The histopathological study established 70μmol/kg luteolin pretreatment markedly attenuates lung histopathological changes, such as haemorrhaging, interstitial edema, and infiltration of polymorphonuclear neutrophils (PMNs) into the lung parenchyma and alveolar spaces. Sufficient evidence for luteolin (35 and 70μmol/kg) suppresses activation and infiltration of PMNs is obtained in expression of surface marker CD11b and Ly6G on cells in bronchoalveolar lavage fluid (BALF) cells and myeloperoxidase activity in lung tissue. Furthermore, luteolin reduces the activity of catalase and superoxide dismutase, and the level of oxidative damage, and lipid peroxidation, in lung tissue. In addition, the secretion of TNF-α, KC, and ICAM-1 in the BALF after LPS challenge are also inhibited by luteolin. Moreover, luteolin reduced LPS-induced activation of MAPK and NFκB pathways. Therefore, luteolin is a potential protective antagonists for LPS-induced ALI in mice., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

As changes in the medical environment and policies on national health insurance coverage have triggered tremendous impacts on the business performance and financial management of medical institutions, effective management becomes increasingly crucial for hospitals to enhance competitiveness and to strive for sustainable development. The study accordingly aims at evaluating hospital operational efficiency for better resource allocation and cost effectiveness. Several data envelopment analysis (DEA)-based models were first compared, and the DEA-artificial neural network (ANN) model was identified as more capable than the DEA and DEA-assurance region (AR) models of measuring operational efficiency and recognizing the best-performing hospital. The classification and regression tree (CART) efficiency model was then utilized to extract rules for improving resource allocation of medical institutions.