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Abstract Backgroud Anti-melanoma differentiation-associated protein 5 antibody-positive dermatomyositis (anti-MDA5-positvie DM) is a subtype of dermatomyositis with a poor prognosis, characterized by rapidly progressive interstitial lung disease (RP-ILD). The study aims to investigate the significance of serum cytokines profiles and peripheral lymphocytes in predicting prognoses of anti-MDA5-positvie DM with RP-ILD. Furthermore, it seeks to analyze longitudinal data of lymphocytes during hospitalization to identify distinct trajectories and cluster patients accordingly. Methods A total of 168 patients with anti-MDA5-positive DM were enrolled in this retrospective study from two cohorts. Univariate and multivariate Cox regression analyses were conducted to determine the predictors of 6-month all-cause mortality and RP-ILD. Group-based trajectory modeling (GBTM) was employed to model the trajectories of longitudinal peripheral lymphocytes. Results In the multivariate Cox regression analysis, IL-6 ≥ 13.41pg/mL, lymphocytes

Abstract Background Cervical cancer is a prevalent malignancy and an important health concern worldwide. Recent research has highlighted the potential impact of metabolic factors, such as hyperlipidemia and diabetes, on cancer progression, increased mortality, and patient outcomes. However, insufficient data have been reported regarding their relationship with cervical cancer. This study aimed to investigate the relationships between metabolic disorders, including dyslipidemia, dysglycemia, and metabolic syndrome, and survival in patients with cervical cancer. Methods We retrospectively analyzed demographic information, clinical characteristics, and metabolic health indicators of patients with cervical cancer. Patients were categorized into groups based on specific metabolic conditions: high triglyceride, high low-density lipoprotein, high cholesterol, and diabetes groups. Additionally, the presence of metabolic syndrome and other metabolic comorbidities was recorded. The log-rank test was used to compare survival rates between different patient groups and identify associated risk factors. Survival curves generated via the Cox proportional hazards model were used to evaluate the associations between metabolic parameters and survival. Results The Cox proportional hazards model was used to analyze data from 840 patients with cervical cancer between 28 and 72 years old who underwent surgery. The hazard ratio (HR) of mortality was 1.804 (95% CI 1.394–2.333, p

Taraxasterol is one of the bioactive ingredients from traditional Chinese herb Taraxacum, which exhibits multiple pharmacological activities and protective effects. However, the underlying influence and mechanism of its use against kidney damage caused from zearalenone (ZEA) remain unexplored. The ZEA-induced kidney damage model of mice was established by feeding diets containing ZEA (2 mg/kg), and taraxasterol (5 and 10 mg/kg) was administered by gavage for 28 days. Results demonstrated taraxasterol increased average daily gain (ADG) and average daily feed intake (ADFI), reduced feed-to-gain ratio (F/G) and kidney index of mice induced by ZEA. Taraxasterol alleviated histopathological changes of kidney, reduced ZEA residue and the levels of blood urea nitrogen (BUN), uric acid (UA), and creatinine (CRE). Concurrently, taraxasterol reduced the contents of oxidative stress indicator reactive oxygen species (ROS) and malondialdehyde (MDA), and increased the activities of antioxidant enzymes catalase (CAT), total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-Px). Further, taraxasterol up-regulated the mRNA and protein expression of nuclear factor erythroid-2-related factor 2 (Nrf2), GSH-Px, NAD(P)H quinone oxidoreductase 1 (NQO1), and heme oxygenase-1 (HO-1), and down-regulated the mRNA and protein expression of KELCH like ECH associated protein (Keap1) in Nrf2/Keap1 pathway. Taraxasterol down-regulated the mRNA and protein expression of immunoglobulin binding protein (Bip), C/EBP homologous protein (CHOP), Bcl-2 associated X (Bax), cysteine protease (Caspase)-12, and Caspase-3, and up-regulated B-cell lymphoma 2 (Bcl-2) expression in endoplasmic reticulum stress pathway. This study suggests that taraxasterol attenuates ZEA-induced mouse kidney damage through the modulation of Nrf2/Keapl pathway to play antioxidant role and endoplasmic reticulum stress pathway to enhance anti-apoptotic ability. It will provide a basis for taraxasterol as a potential drug to prevent and treat ZEA-induced kidney damage.

Jingmen tick virus (JMTV) is a newly identified segmented flavivirus that has been recognized in multiple hosts, such as humans, buffalos, bats, rodents, mosquitos and ticks. Various clinical cases and studies manifested that JMTV is a true arbovirus with wide host spectrum and showed potential threats toward public health. JMTV has been reported in multiple countries in Asia, Europe, Africa, and America. Moreover, wild boars serve as an important intermediary between humans and the wild ecological system. In China, it has been reported in nine provinces, while the prevalence and the distribution of JMTV in most regions including Jiangxi Province are still unknown. Thus, to profile the distribution of JMTV in Jiangxi Province, an epidemiological investigation was carried out from 2020 to 2022. In current study, 66 ticks were collected from 17 wild boars in Jiangxi Province. The results showed that 12 out of 66 ticks were JMTV positive, indicating JMTV is prevalent in ticks and boars in Jiangxi Province. The genome sequences of JMTV strain WY01 were sequenced to profile viral evolution of JMTV in China. Phylogenetic analysis divided JMTV strains into two genotypes, Group I and Group II. WY01 belongs to Group II and it shares the closest evolutionary relationship with the Japan strains rather than the strains from neighboring provinces in China suggesting that JMTV might have complex transmission routes. Overall, current study, for the first time, reported that JMTV is prevalent in Jiangxi Province and provided additional information concerning JMTV distribution and evolution in China.

Background: Glioblastoma (GBM) is a common and highly aggressive brain tumor with a poor prognosis for patients. It is urgently needed to identify potential small molecule drugs that specifically target key genes associated with GBM development and prognosis.Methods: Differentially expressed genes (DEGs) between GBM and normal tissues were obtained by data mining the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Gene function annotation was performed to investigate the potential functions of the DEGs. A protein-protein interaction (PPI) network was constructed to explore hub genes associated with GBM. Bioinformatics analysis was used to screen the potential therapeutic and prognostic genes. Finally, potential small molecule drugs were predicted using the DGIdb database and verified using chemical informatics methods including absorption, distribution, metabolism, excretion, toxicity (ADMET), and molecular docking studies.Results: A total of 429 DEGs were identified, of which 19 hub genes were obtained through PPI analysis. The hub genes were confirmed as potential therapeutic targets by functional enrichment and mRNA expression. Survival analysis and protein expression confirmed centromere protein A (CENPA) as a prognostic target in GBM. Four small molecule drugs were predicted for the treatment of GBM.Conclusion: Our study suggests some promising potential therapeutic targets and small molecule drugs for the treatment of GBM, providing new ideas for further research and targeted drug development.

Due to the rise in temperature and sea level caused by climate change, the detection rate of aflatoxin B1 (AFB1) in food crops has increased dramatically, and the frequency and severity of aflatoxicosis in humans and animals are also increasing. AFB1 has strong hepatotoxicity, causing severe liver damage and even cancer. However, the mechanism of AFB1 hepatotoxicity remains unclear. By integrating network toxicology, molecular docking and in vivo experiments, this research was designed to explore the potential hepatotoxicity mechanisms of AFB1. Thirty-three intersection targets for AFB1-induced liver damage were identified using online databases. PI3K/AKT1, MAPK, FOXO1 signaling pathways, and apoptosis were significantly enriched. In addition, the proteins of ALB, AKT1, PIK3CG, MAPK8, HSP90AA1, PPARA, MAPK1, EGFR, FOXO1, and IGF1 exhibited good affinity with AFB1. In vivo experiments, significant pathological changes occurred in the liver of mice. AFB1 induction increased the expression levels of EGFR, ERK, and FOXO1, and decreased the expression levsls of PI3K and AKT1. Moreover, AFB1 treatment caused an increase in Caspase3 expression, and a decrease in Bcl2/Bax ratio. By combining network toxicology with in vivo experiments, this study confirms for the first time that AFB1 promotes the FOXO1 signaling pathway by inactivating PI3K/AKT1 and activating EGFR/ERK signaling pathways, hence aggravating hepatocyte apoptosis. This research provides new strategies for studying the toxicity of environmental pollutants and new possible targets for the development of hepatoprotective drugs.

The 20 μg (0–1–6 month) hepatitis B virus (HBV) vaccination is widely recommended for HBV vaccine-naïve immune adults in China. However, suboptimal protective responses may occur due to dose-series incompletion. We aim to investigate the immunogenicity of a 60 μg HB vaccine with a 0–2 month series among HBV vaccine-naïve immune adults aged 25–55 to assess potential alternative approaches for HB immunization. A two-center randomized controlled trial was carried out. Participants were randomly allocated to either the 20 μg (0–1–6 month) or the 60 μg (0–2 month) regimen. Blood samples were collected eight weeks after the final injection to measure the antibodies. A total of 583 adults (289 in the 20 μg regimen and 294 in the 60 μg regimen) were included. The seroprotection rates (SPRs) were 97.23% and 93.54% in the 20 μg and 60 μg regimens, respectively (p = 0.0261), and the geometric mean concentrations were 600.76 mIU/mL and 265.68 mIU/mL, respectively (p < 0.0001). The immunogenicity of the 60 μg regimen decreased significantly with age, particularly in adults aged 40 and older. The 60 μg regimen may be beneficial for adults under 40, especially those with poor compliance or in urgent need of immunization.

In recent years, the growing incidence of health issues among Chinese students, including obesity, diabetes, and other chronic diseases, has been attributed to a sedentary lifestyle, lack of physical activity, and unhealthy eating habits. Physical education (PE) classes play a crucial role in promoting physical activity and fostering healthy lifestyles among Chinese students. The purpose of this study was to investigate the influence of the healthy PE curriculum model on the sports ability of senior high school students in China. The trial adopted a quasi-experimental design with equivalent groups. The experimental group followed the healthy PE curriculum model in their PE classes, while the control group received traditional technical instruction. During the 12-week intervention, 149 senior high school students completed the sports ability test as both the pre-test and post-test measurements for this experimental study. The results indicated that the experimental group showed significant improvements in sports ability compared to the control group, highlighting the positive effects of the healthy PE curriculum model. The structural characteristics of the healthy PE curriculum model provided essential support for students' learning and proved to be an effective way to promote physical literacy among senior high school students in China.

Objective Tracheobronchial tuberculosis (TBTB), a specific subtype of pulmonary tuberculosis (PTB), can lead to bronchial stenosis or bronchial occlusion if not identified early. However, there is currently no available means for predicting the risk of associated TBTB in PTB patients. The objective of this study was to establish a risk prediction nomogram model for estimating the associated TBTB risk in every PTB patient.Methods A retrospective cohort study was conducted with 2153 PTB patients. Optimised characteristics were selected using least absolute shrinkage and selection operator regression. Multivariate logistic regression was applied to build a predictive nomogram model. Discrimination, calibration and clinical usefulness of the prediction model were assessed using C-statistics, receiver operator characteristic curves, calibration plots and decision analysis. The developed model was validated both internally and externally.Results Among all PTB patients who underwent bronchoscopies (n=2153), 40.36% (n=869) were diagnosed with TBTB. A nomogram model incorporating 11 predictors was developed and displayed good discrimination with a C-statistics of 0.782, a sensitivity of 0.661 and a specificity of 0.762 and good calibration with a calibration-in-the-large of 0.052 and a calibration slope of 0.957. Model’s discrimination was favourable in both internal (C-statistics, 0.782) and external (C-statistics, 0.806) validation. External validation showed satisfactory accuracy (sensitivity, 0.690; specificity, 0.804) in independent cohort. Decision curve analysis showed that the model was clinically useful when intervention was decided on at the exacerbation possibility threshold of 2.3%–99.2%. A clinical impact curve demonstrated that our model predicted high-risk estimates and true positives.Conclusion We developed a novel and convenient risk prediction nomogram model that enhances the risk assessment of associated TBTB in PTB patients. This nomogram can help identify high-risk PTB patients who may benefit from early bronchoscopy and aggressive treatment to prevent disease progression.

Abstract Fibroblast-like synoviocytes (FLSs), play a key role in perpetuating synovial inflammation and bone erosion in rheumatoid arthritis (RA), however, the underlying mechanism(s) of RA FLSs activation and aggression remain unclear. Identifying endogenous proteins that selectively target FLSs is urgently needed. Here, we systematically identified that secreted modular calcium-binding protein 2 (SMOC2), was significantly increased in RA FLSs and synovial tissues. SMOC2 knockdown specifically regulated cytoskeleton remodeling and decreased the migration and invasion of RA FLSs. Mechanistically, cytoskeleton-related genes were significantly downregulated in RA FLSs with reduced SMOC2 expression, especially the motor protein myosin1c (MYO1C). SMOC2 controlled MYO1C expression by SRY-related high-mobility group box 4 (SOX4) and AlkB homolog 5 (ALKHB5) mediated-m6A modification through transcriptional and post-transcriptional regulation. Furthermore, intra-articular Ad-shRNA-SMOC2 treatment attenuated synovial inflammation as well as bone and cartilage erosion in rats with collagen-induced arthritis (CIA). Our findings suggest that increased SMOC2 expression in FLSs may contribute to synovial aggression and joint destruction in RA. SMOC2 may serve as a potential target against RA. SMOC2-mediated regulation of the synovial migration and invasion in RA FLSs. In RA FLSs, SMOC2 is significantly increased, leading to the increased level of MYO1C via SOX4-mediated transcriptional regulation and ALKBH5-mediated m6A modification, thereby causing cytoskeleton remodeling and promoting RA FLSs migration and invasion. The Figure was drawn by Figdraw.

Objectives: The Mycobacterium avium complex (MAC), comprising a series of subspecies, has a worldwide distribution, with differences in drug susceptibility among subspecies. This study aimed to assess the composition of MAC and susceptibility differences among subspecies in mainland China. Methods: A total of 287 MAC clinical strains were included in the study. Multitarget sequences were applied to accurately identify subspecies, and a microdilution method was used to evaluate minimum inhibitory concentrations (MICs) among subspecies using Sensititre SLOMYCO plates. Results: Mycobacterium intracellular (N = 169), Mycobacterium avium (N = 52), Mycobacterium chimaera (N = 22), Mycobacterium marseillense (N = 25), Mycobacterium colombiense (N = 14), Mycobacterium yongonense (N = 4), Mycobacterium vulneris (N = 3) and Mycobacterium timonense (N = 2) were isolated from MAC. Clarithromycin, amikacin and rifabutin showed lower MIC50 and MIC90 values than other drugs, and the resistance rates of clarithromycin, amikacin, linezolid and moxifloxacin were 6.3%, 10.5%, 51.9% and 46.3%, respectively. The resistance rates of clarithromycin and moxifloxacin in the initial treatment group were significantly lower than those in the retreatment group (4.09% vs. 12.94%; 30.41% vs. 75.29%; P < 0.05). Drug susceptibility differences were observed in clarithromycin and moxifloxacin among the five major subspecies (P < 0.05); however, those statistically significant differences disappeared when MACs were divided into two groups according to previous anti-tuberculosis (anti-TB) treatment history. Conclusion: This study revealed that MAC, primarily comprising M. intracellulare, was susceptible to clarithromycin, amikacin and rifabutin. Drug susceptibility among subspecies did not exhibit intrinsic differences in our study. Previous anti-TB treatment patients are more resistant to drugs; thus, attention should be given to those patients in the clinic.

The segmentation of knee joint is of great significance for diagnosis, guidance and treatment of knee osteoarthritis. However, manual delineation is time-consuming and labor-intensive since various anatomical structures are involved in the 3D MRI volume. Automatic segmentation of the whole knee joint requires no human effort, additionally can improve the quality of arthritis diagnosis and treatment by describing the details more accurately. Existing knee joint segmentation methods in the literature focus on only one or few structures out of many. In this paper, we study the feasibility of knee joint segmentation on MR images based on neural networks and deal with the following challenges: (1) end-to-end segmentation of 15 anatomical structures, including bone and soft tissue, of the whole knee on MR images; (2) robust segmentation of small structures such as the anterior cruciate ligament, accounting for about 0.036% of the volume data. Experiments on the knee joint MR images demonstrate that the average segmentation accuracy of our method achieves 92.92%. The Dice similarity coefficients of 9 structures were above 94%, five structures were between 87% and 90%, and the remaining one was about 76%.

Abstract Lymph nodes (LNs) are frequently the first sites of metastasis. Currently, the only prognostic LN assessment is determining metastatic status. However, there is evidence suggesting that LN metastasis is facilitated by the formation of a pre‐metastatic niche induced by tumour derived extracellular vehicles (EVs). Therefore, it is important to detect and modify the LN environmental changes. Earlier work has demonstrated that neutrophil extracellular traps (NETs) can sequester and promote distant metastasis. Here, we first confirmed that LN NETs are associated with reduced patient survival. Next, we demonstrated that NETs deposition precedes LN metastasis and NETs inhibition diminishes LN metastases in animal models. Furthermore, we discovered that EVs are essential to the formation of LN NETs. Finally, we showed that lymphatic endothelial cells secrete CXCL8/2 in response to EVs inducing NETs formation and the promotion of LN metastasis. Our findings reveal the role of EV‐induced NETs in LN metastasis and provide potential immunotherapeutic vulnerabilities that may occur early in the metastatic cascade.

Aim: To understand academic support structures for Washington state public high school students with concussion during the COVID-19 pandemic. Materials & methods: Prospective, repeated cross-sectional study of 21 schools in 2020 and 2021. Results: About 28% of schools reported not providing any return-to-learn (RTL) accommodations for students with concussion throughout the COVID-19 pandemic. RTL accommodation provision was associated with larger student body size (β = 0.002) and higher graduation rate (β = 0.261) but was not associated with presence of RTL school policy. About 38.1% of schools received no guidance on how to provide RTL accommodations during the COVID-19 pandemic, and many reported that students with concussion struggled more. Conclusion: Schools struggled to provide RTL accommodations for students with concussion during the COVID-19 pandemic, highlighting the need for evidence-based guidance and resource allocation to vulnerable schools.

Abstract Background Blood transcriptomics can be used for confirmation of tuberculosis diagnosis or sputumless triage, and a comparison of their practical diagnostic accuracy is needed to assess their usefulness. In this study, we investigated potential biomarkers to improve our understanding of the pathogenesis of active pulmonary tuberculosis (PTB) using bioinformatics methods. Methods Differentially expressed genes (DEGs) were analyzed between PTB and healthy controls (HCs) based on two microarray datasets. Pathways and functional annotation of DEGs were identified and ten hub genes were selected. They were further analyzed and selected, then verified with an independent sample set. Finally, their diagnostic power was further evaluated between PTB and HCs or other diseases. Results 62 DEGs mostly related to type I IFN pathway, IFN-γ-mediated pathway, etc. in GO term and immune process, and especially RIG-I-like receptor pathway were acquired. Among them, OAS1, IFIT1 and IFIT3 were upregulated and were the main risk factors for predicting PTB, with adjusted risk ratios of 1.36, 3.10, and 1.32, respectively. These results further verified that peripheral blood mRNA expression levels of OAS1, IFIT1 and IFIT3 were significantly higher in PTB patients than HCs (all P

The isothermal constant strain rate compression test of Ti-4.2Al-0.005B titanium alloy was carried out by Gleeble-3800 thermal simulator at temperature 850∼1050 °C, strain rate 0.001∼10s−1 and maximum deformation degree 60%. According to the experimental data, the Arrhenius constitutive model was established, the flow stress curve was analyzed, and the processing map based on polarity reciprocity model was established, which was further optimized by Zener-Hollomon parameter processing map and activation energy map. The results show that the flow stress curves respectively show dynamic recovery characteristics and dynamic softening characteristics under different deformation conditions respectively. The softening behavior of the flow stress curves under high strain rate is caused by temperature effect, while the softening behavior at low strain rate is caused by dynamic recrystallization. According to the established Polar Reciprocity Model processing map, the stable region is (870–990 °C/0.01–0.12s−1). Then, the Zener-Hollomon parameter processing map and activation energy processing map were established. Finally, the optimal processing parameters of the alloy are (870–990 °C/0.04–0.12s−1). The main deformation mechanism is dynamic recrystallization. Meanwhile, the rationality of Zener-Hollomon parameter diagram and activation energy diagram is verified. In the actual production process, the choice of technological parameters is provided in order to obtain good microstructure and properties.

Rheumatoid arthritis is considered a chronic systemic autoimmune disorder that may cause joint destruction. Triptolide, an active component isolated from Tripterygium wilfordii Hook.f., is considered to have promising potential for clinical use in treating rheumatoid arthritis. However, its clinical application has been limited by the narrow therapeutic window, side effects associated with plasma drug fluctuations, low oral bioavailability, and poor patient compliance with the long and frequent dosing regimen. An extended drug release preparation may address these limitations. The aim of this work was therefore to develop, formulate and optimize sustained release triptolide microspheres with poly (lactide-co-glycolide) (PLGA). Triptolide-loaded microspheres were prepared using PLGA as the matrix polymer, dichloromethane as the oil phase, and polyvinyl alcohol (PVA) as the matrix forming emulsifier. An oil-in-water (O/W) emulsion solvent evaporation technique was utilized to prepare the microspheres. Surface response methodology (RSM) coupled with central composite design (CCD) was used to optimize the formulation and a total of twenty formulations were prepared. PVA concentration (X1), PLGA concentration (X2), and theoretical drug content (X3) were selected as independent variables; and drug content (Y1), encapsulation efficiency (Y2), mean diameter (Y3) and the initial release during the first day (Y4) were taken as the response variables. The optimized formulation showed mean diameter of 42.36 μm, drug content of 7.96%, encapsulation efficiency of 80.16% and an initial release of 14.48%. The prepared microspheres exhibited a sustained release profile of triptolide in vitro over 4 weeks, which was wellfitted with a Korsmeyer-Peppas equation. However, the initial drug release (~14%) of triptolide-loaded microspheres was very high and should be specifically investigated in future studies. The results indicate that long-term sustained release microspheres of triptolide can be considered a strategy to overcome the low bioavailability and poor patient compliance with conventional triptolide tablets. The issue of initial burst release and in vivo evaluations should be specifically investigated in the future.

In this study, the chloroplast (Cp) genome of Zanthoxylum avicennae (Lam.) DC was sequenced by high-throughput sequencing technology. The length of the Cp genome of Zanthoxylum avicennae was 158,568 bp, and the total GC content was 38.4%, including a large single-copy (LSC) region of 86,318 bp, a small single-copy (SSC) region of 18,250 bp, and 27,000 bp of inverted repeats (IRs). The Cp genome encoded 131 genes, including 88 protein-coding, 37 tRNA, and six rRNA genes. Phylogenetic analysis of the genome sequence showed that Zanthoxylum avicennae was closely related to Zanthoxylum nitidum, Zanthoxylum esquirolii and Zanthoxylum motuoense of the Rutaceae family.

The Gleeble-3800 thermal simulator is used to perform isothermal and constant strain rate compression tests on SP700 titanium alloy under the conditions of deformation temperature of 700–950 °C and strain rate of 0.001–1 s−1. The processing map technology can be obtained based on dynamic material model, through this technology, its thermal deformation behavior can be studied and the appropriate processing parameter range can be optimized by combining the changes in the strain rate sensitivity exponent m, strain hardening exponent n and deformation activation energy Q. The results show that the flow stress of SP700 titanium alloy is sensitive to deformation temperature and strain rate. When the strain is 0.9, the strain rate sensitivity exponent m is greater than 0.5 when the deformation temperature is 800 °C and the strain rate is 0.001 s−1 and 1 s−1. Under this condition, the SP700 titanium alloy may have superplastic deformed. In addition, the analysis shows that when the deformation temperature is 775–825 °C, the strain rate is 0.3–1 s−1 and 0.001–0.002 s−1, this condition is the best processing parameter range of SP700 titanium alloy.

Health behaviors influence health and well-being, improve quality of life, and provide economic benefits. It is important to take advantage of health-related opportunities during adolescence. Staying healthy during adolescence also promotes the future well-being of individuals and that of the next generation. We aimed to develop a reliable and valid scale based on the General Senior High School Physical Education and Health Curriculum Standards (2017 edition) to evaluate Chinese late adolescents’ health behavior. The scale was to help physical education teachers measure the health behavior level of senior high school students, improve physical education and health teaching, and promote Chinese adolescent health. Participants were recruited by convenience sampling from September to October 2019. For the first survey, we recruited 526 senior high school students (318 boys, 208 girls; Mage = 16.5), and the data were subjected to item analysis and exploratory factor analysis. For the second survey, we recruited 542 senior high school students (249 boys, 293 girls; Mage = 15.5), and the data were subjected to confirmatory factor analysis and internal consistency reliability analysis. After exploratory factor analysis, we extracted four factors with 23 items: exercise awareness and habits (five items), mastering and applying healthy behavior knowledge (10 items), emotional regulation (four items), and environment adaptation (four items). The Cronbach’s alpha values for these factors ranged from 0.863 to 0.937. After confirmatory factor analysis, we achieved a satisfactory goodness-of-fit model (CMIN/DF = 2.92, RMR = 0.03, GFI = 0.93, CFI = 0.91, TLI = 0.92, RMSEA = 0.06). Internal consistency, test–retest reliability, and construct validity were all satisfactory. These results suggest that the Chinese version of the Health Behavior Scale is a reliable and valid instrument for assessing the health behavior of senior high school students. The findings have important implications for increasing adolescents’ health literacy, promoting adolescents’ health, and enhancing the well-being of late adolescents.

Abstract Filifolium sibiricum (L.)Kitam (F. sibiricum), a compositae plant, is especially used to inhibit drug-resistant bacteria in folk medicine. Modern pharmacological studies also confirmed a variety of pharmacological properties about sedative activities, antibacterial activity, anti-inflammatory activity, analgesic activities, antitussive and asthma relieving. In this paper, the research progress of F. sibiricum in botany, ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics and toxicology was reviewed. Prospects for future investigation and application of this herb were also discussed. Information on F. sibiricum was gathered from various sources, including books on traditional Chinese herbal medicine and scientific databases such as PubMed, Google Scholar, Science Direct, Baidu Scholar, CNKI and other professional websites. The results indicate that ~ 66 chemical compounds were isolated and identified from F. sibiricum. Among them, flavonoids are generally considered to be the main bioactive and characteristic ingredients. F. sibiricum is a traditional Chinese medicine with pharmacological activities such as the immune system, nervous system, respiratory system and cardiovascular and cerebrovascular systems. Most importantly, we should concentrate on developing new drugs related to F. sibiricum, so as to exert greater potential for treatment.

Objective: To explore the effect and underlying mechanism of Myricitrin (Myr) in regulating fibroblast-like synoviocyte (FLS)-mediated synovitis and joint destruction in RA.Methods: FLSs were isolated from synovial tissues from patients with RA. Gene expression was measured using quantitative RT-qPCR. Protein expression was detected by immunohistochemistry or Western blot. Cell apoptosis was performed by an Annexin-PI staining assay. EdU incorporation was used to assess the proliferation of RA FLS. Transwell assay was used to characterize the cell migration and invasion ability of RA FLS. The potential target of Myr was identified by RNA sequencing analysis. The in vivo effect of Myr was assessed in a collagen-induced arthritis (CIA) model.Results: Myr treatment inhibited the lamellipodia formation, migration, and invasion, but not the apoptosis and proliferation, of RA FLSs. Myr also reduced the expression of CCL2, IL-6, IL-8, MMP-1, MMP-3, and MMP-13 induced by TNF-α. The RNA-seq results indicated that AIM2 may be a target gene of Myr in RA FLSs. Furthermore, compared to healthy controls, AIM2 expression showed higher levels in synovial tissues and FLSs from RA patients. AIM2 knockdown also inhibited RA FLS migration, invasion, cytokine, and MMP expression. In addition, either Myr treatment or AIM2 knockdown reduced the phosphorylation of AKT induced by TNF-α stimulation. Importantly, Myr administration relieved arthritis symptoms and inhibited AIM2 expression in the synovium of CIA mice.Conclusion: Our results indicate that Myr exerts an anti-inflammatory and anti-invasion effect in RA FLSs and provide evidence of the therapeutic potential of Myr for RA.

Hepatitis B (HB) vaccination is recommended for people with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). We aimed to assess the immune response to the HB vaccine and associated factors using the standard vaccination schedule among people with HIV (PWH) in China. A prospective study was carried out from 2016 to 2020 in Beijing, China. PWH were given three 20 μg doses of recombinant HB vaccine at 0, 1, and 6 months. Blood samples were taken within 4–6 weeks after each dose to evaluate the anti-HBs levels. A total of 312 participants completed vaccination and serologic testing. The seroconversion (anti-HBs ≥ 10 IU/L) rates following the first, second, and third doses of the vaccine were 35.6% (95% CI: 30.3–40.9%), 55.1% (95% CI: 49.6–60.7%), and 86.5% (95% CI: 82.8–90.3%), respectively, and the geometric means of the anti-HBs titers were 0.8 IU/L (95% CI: 0.5–1.6 IU/L), 15.7 IU/L (95% CI: 9.4–26.3 IU/L), and 241.0 IU/L (95% CI: 170.3–341.1 IU/L), respectively. In multivariate analysis, after three doses of vaccination, age, CD4 cell count, and HIV-RNA viral load were significantly associated with strong, moderate, and weak response, respectively. These findings confirm that these personal health conditions are related to the HB response. HB vaccination in PWH using the standard schedule was still highly effective in the context of early treatment initiation, especially among participants aged 30 years and younger.

Abstract Objectives Ischemia–reperfusion injury is harmful in partial nephrectomy (PN) in renal cell carcinoma. Choosing an appropriate surgical method is important to reduce ischemia–reperfusion injury. This study aimed to compare the effect of segmental artery clamping (SAC) and main renal artery clamping (MAC) on patients who underwent PN. Methods Studies from January 2008 to November 2019 were identified by an electronic search of English and Chinese databases, including PubMed, Excerpt Medica Database, Cochrane Library, Wanfang, VIP, and Chinese National Knowledge Internet, without language restriction. Two reviewers were involved in the trial. The effects on operation time (OT), warm ischemia time (WIT), length of hospital stay (LOS), blood transfusion rate, postoperative complication rate, Clavien classification (≥ 3), and positive surgery margin (PSM) were evaluated using Stata software. Standardized mean difference (SMD, for continuous data) and pooled odds ratios (for count data) with 95% confidence interval (CI) were used as effect indicators. Results Thirty-two studies were included. SAC decreased the 1-week (SMD = − 0.973; 95% CI = − 1.414, − 0.532; P = 0.000), 1-month (SMD = − 0.411; 95% CI = − 0.769, − 0.053; P = 0.025), and 3-month (affected kidney: SMD = − 0.914; 95% CI = − 1.662, − 0.617; P = 0.000) percentages of postoperative changes in renal function (estimated glomerular filtration rate) between the SAC and MAC groups. Sub-group analysis showed that the SAC group had longer OT (SMD = 0.562; 95% CI = 0.252, 0.871; P = 0.000) than the MAC group. However, no differences were observed in the OT, WIT, LOS, blood transfusion rate, postoperative complication rate, Clavien classification (≥ 3), and PSM between the two groups. Conclusions SAC is superior to MAC in terms of short-term postoperative renal function recovery. The use of SAC or MAC depends on tumor size, location, surgical modality, and surgeon’s judgments.

Podophyllotoxin (PPT) has shown strong antitumor effects on various types of cancers. However, the non-specific toxicity and poor solubility severely limits its clinical transformation. In order to overcome the adverse properties of PPT and explore its clinical potential, three novel PTT−fluorene methanol prodrugs linked by different lengths of disulfide bonds were designed and synthesized. Interestingly, the lengths of the disulfide bond affected the drug release, cytotoxicity, pharmacokinetic characteristics, in vivo biodistribution and antitumor efficacy of prodrug NPs. To be more specific, all three PPT prodrugs could self-assemble into uniform nanoparticles (NPs) with high drug loading (>40%) via the one-step nano precipitation method, which not only avoids the use of surfactants and cosurfactants, but also reduces the systemic toxicity of PPT and increases the tolerated dose. Among the three prodrug NPs, FAP NPs containing α-disulfide bond showed the most sensitive tumor-specific response and fastest drug release rate, thus demonstrating the strongest in vitro cytotoxicity. In addition, three prodrug NPs showed prolonged blood circulation and higher tumor accumulation. Finally, FAP NPs demonstrated the strongest in vivo antitumor activity. Our work will advance the pace of podophyllotoxin towards clinical cancer treatment.

Cabazitaxel (CTX) has distinct therapeutic merits for advanced and metastatic cancer. However, the present clinical formulation (Jevtana®) has several defects, especially for undesirable tumor-targeting and serious side effects, greatly limiting the therapeutic efficacy. Small-molecule prodrug-based nanoassemblies integrate the advantages of both prodrug strategy and nanotechnology, emerging as a promising treatment modality. Herein, disulfide bonds with different lengths were employed as linkages to elaborately synthesize three redox-sensitive stearyl alcohol (SAT)-CTX prodrug-based nanoassemblies (SAC NPs, SBC NPs and SGC NPs) for seeking optimal chemotherapeutical treatment. All the prodrug-based nanoassemblies exhibited impressive drug-loading efficiency, superior self-assembly capability and excellent colloidal stability. Interestingly, the drug release behaviors of three prodrug-nanoassemblies in the same reductive environment were different owing to tiny changes in the carbon chain length of disulfide bonds, resulting in disparate cytotoxicity effects, pharmacokinetic outcomes and in vivo antitumor efficacies. Among them, SAC NPs displayed rapid drug release, excellent cytotoxicity, long blood circulation and enhanced tumor accumulation, thus showing strong tumor inhibition in the 4T1-bearing mouse model. Our study shed light on the vital role of connecting bonds in designing high-efficiency, low-toxicity prodrug nanoassemblies.

Background Angioembolization has been the gold standard for management of pelvic arterial bleeding, but applicability has been limited by delays in access at many trauma centers. We hypothesized that a quality improvement program to reduce time to start of angiography would be associated with lower in-hospital mortality in patients with pelvic fractures and shock.Methods Retrospective study of adults with a pelvic fracture and vital signs consistent with shock admitted to a level I trauma center after the initiation of a quality improvement project to reduce the time to angioembolization (2012 to 2016). Time from admission to procedure start for hemorrhage control was examined based on destination and time of day. In-hospital mortality was the primary outcome and was compared with US benchmarks in the literature.Results The study group included 424 patients with a mean Injury Severity Score of 41±14. Of these, 212 (50%) responded to resuscitation and were admitted to the intensive care unit; 143 (34%) patients went directly to interventional radiology (IR) with a median time to start of angiography of 86 minutes (IQR 66 to 116); and 69 (16%) patients went directly to the OR with a median time to start of operation of 52 minutes (IQR 37 to 73). There were no significant differences in time to procedures based on time of day or transfer status. In-hospital mortality for patients in shock on admission was 15%.Discussion Patients with pelvic fracture and hemorrhagic shock, with a median time to angioembolization of

Optimization relates to the ultimate yield strength and the maximum stress incident on the current model under critical working conditions and finds through iterative processing a way to compensate for the strength requirement without going beyond the desired mass limits. In this paper, the horizontal sheet metal base of a horizontal toggle clamp is optimised for mass reduction using the finite element analysis in the computer aided design software. The sheet metal base material is the ANSI32 Steel. In the design software, it is designed with the thickness of 7 mm and it is intended to support a workload of up to 750 N. The constraints were a fixed point added at all the holes and at the bottom surface of the sheet metal base. A number of iterations were made for the 750N loading force across the base plate to run the simulation. For optimization, the aim was to minimize the mass of the base plate. The design parameters were Von Mises, factor of safety and displacement. The variables were the slots’ width and material thickness along the mid-surface of the sheet metal. The mass was reduced by more than thirty per cent overall.

Objectives: To study in-depth the clinical and epidemiological characteristics of pneumonia resulting from COVID-19 and provide evidence for effective public health decisions.Methods: This was a retrospective, single-center research study. Participants were enrolled from patients presenting at the Chongqing Public Health Medical Treatment Center from Jan 24 to Feb 7, 2020, and were confirmed as having COVID-19.Results: A total of 114 COVID-19 patients (99 mild, 4 severe, 11 critical) of which 56 (56/114; 49.1%) were male, 58 (58/114; 50.9%) were female with a mean age of 46.05 years. Twenty nine (29/114; 25.44%) patients suffered from chronic diseases. Neutrophils counts in 23.68% (27/114) of patients were abnormally low and abnormally high in 21.05% (24/114). Erythrocyte sedimentation rate and the C-reactive protein levels were abnormally elevated in 76.5% (62/81) and 62.9% (66/105) of patients, respectively. Creatine kinase isoenzymes (CK-MB), pro-brain natriuretic peptide (pro-BNP) and troponin levels were above the normal range in 7.10% (8/112), 66.7% (10/15), and 100% of patients, respectively. The percentage of patients in which the partial pressure of oxygen (PaO2)/fraction of inspired O2(FiO2) ratio exceeded 200 was 60%. A total of 91 (91/114; 79.82%) patients displayed severe bilateral pneumonia, 52 (52/114; 45.61%) exhibited ground-glass opacity, and pulmonary consolidation was observed in 4 (3.51%) patients. Differences in shortness of breath, insomnia, inappetence, the procalcitonin (PCT) levels, FiO2 and PaO2/FiO2 among the three groups were statistically significant (p < 0.05). Differences between the mild and severe groups was observed in neutrophil and lymphocyte counts, CD4 expression, and levels of C-reactive protein, alanine aminotransferase, aspartate aminotransferase and albumin (P < 0.05). Between the mild and critical groups, differences were observed in neutrophils, platelets, and CD4 expression (P < 0.05). A difference in C-reactive protein levels between severe and critical groups was also found (P < 0.05).Conclusions: In the majority of cases no gender differences were observed and mostly the symptoms were mild. Evidence of efficient human-to-human virus transmission was found. The elderly with comorbidities were more prone to develop into severe or critical illness. Age and comorbidity may be risk factors for poor outcome.

Evidence on the effectiveness of hepatitis B virus (HBV) infection screening and vaccination programs remains rare in China. We used a quasi-experimental method, propensity score matching, to evaluate the effects of a community-based HBV infection detection combined with vaccination (HBVIDV) program in a pilot. Data were retrieved from the HBVIDV program implemented between July 2019 and June 2020. Outcomes were the difference between the treatment and control groups in hepatitis B vaccination (≥1 dose), hepatitis B vaccine series completion (≥3 doses), and serologic evidence of vaccine-mediated immunity. Altogether, 26,180 individuals were included, where 6160 (23.5%) individuals were assigned to the treatment group, and 20,020 (76.5%) individuals were assigned to the control group. After propensity score matching, 5793 individuals were matched. The rates of hepatitis B vaccination, hepatitis B vaccine series completion, and prevalence of vaccine-mediated immunity in the treatment and control groups were 29.0% vs. 17.8%, 22.1% vs. 13.1%, and 38.2% vs. 27.6%, respectively. The HBVIDV program was significantly associated with increased hepatitis B vaccination rate (OR, 1.884, 95% CI 1.725–2.057), hepatitis B vaccine series completion rate (OR, 1.872, 95% CI 1.696–2.065), and prevalence of vaccine-mediated immunity (OR, 1.623, 95% CI 1.501–1.755). The greater magnitude of association between HBVIDV program and outcomes was observed among adults aged 35–54 years and adults who live in rural areas. The HBVIDV program was effective in increasing the hepatitis B vaccination rate, hepatitis B vaccine series completion rate, and prevalence of vaccine-mediated immunity among adults in the pilot. Further focusing the program on special populations and regions may produce more effective results.

Since effective chemotherapeutics or preventive measures are still unavailable, finding feasible approaches against white spot syndrome virus (WSSV) has always been the vital subject in shrimp farming field. Envelope proteins are the ideal targets for antiviral strategies development due to their indispensable roles in virus entry, and inhibitory peptides targeting them have been proved to be promising in blocking virus infection. In this study, the Wimley-White interfacial hydrophobicity scale (WWIHS) in combination with known structural data was applied to identify potential inhibitory peptides that targeted the envelope protein VP28 of WSSV. Results showed that two potential inhibitory peptides were identified, one of which exhibited not only obvious antiviral activity, but also broad-spectrum antimicrobial activity. The inhibitory peptide identified here can serve as a lead compound for anti-WSSV strategies development. Keywords: Envelope protein, Inhibitory peptide, White spot syndrome virus, Shrimp

Introduction: Photoplethysmography (PPG) has been widely used to assess cardiovascular function. However, few studies have comprehensively investigated the effect of measurement site on PPG waveform characteristics. This study aimed to provide a quantitative comparison on this.Methods: Thirty six healthy subjects participated in this study. For each subject, PPG signals were sequentially recorded for 1 min from six different body sites (finger, wrist under (anatomically volar), wrist upper (dorsal), arm, earlobe, and forehead) under both normal and deep breathing patterns. For each body site under a certain breathing pattern, the mean amplitude was firstly derived from recorded PPG waveform which was then normalized to derive several waveform characteristics including the pulse peak time (Tp), dicrotic notch time (Tn), and the reflection index (RI). The effects of breathing pattern and measurement site on the waveform characteristics were finally investigated by the analysis of variance (ANOVA) with post hoc multiple comparisons.Results: Under both breathing patterns, the PPG measurements from the finger achieved the highest percentage of analyzable waveforms for extracting waveform characteristics. There were significant effects of breathing pattern on Tn and RI (larger Tn and smaller RI with deep breathing on average, both p < 0.03). The effects of measurement site on mean amplitude, Tp, Tn, and RI were significant (all p < 0.001). The key results were that, under both breathing patterns, the mean amplitude from finger PPG was significantly larger and its Tp and RI were significantly smaller than those from the other five sites (all p < 0.001, except p = 0.04 for the Tp of “wrist under”), and Tn was only significantly larger than that from the earlobe (both p < 0.05).Conclusion: This study has quantitatively confirmed the effect of PPG measurement site on PPG waveform characteristics (including mean amplitude, Tp, Tn, and RI), providing scientific evidence for a better understanding of the PPG waveform variations between different body sites.

ObjectiveTo investigate the role of glycogen metabolism in regulating rheumatoid fibroblast-like synoviocyte (FLS)-mediated synovial inflammation and its underlying mechanism.MethodsFLSs were separated from synovial tissues (STs) obtained from rheumatoid arthritis (RA) patients. Glycogen content was determined by periodic acid Schiff staining. Protein expression was analyzed by Western blot or immunohistochemistry. Gene expression of cytokines and matrix metalloproteinases (MMPs) was evaluated by quantitative real-time PCR. FLS proliferation was detected by EdU incorporation. Migration and invasion were measured by Boyden chamber assay.ResultsGlycogen levels and glycogen synthase 1 (GYS1) expression were significantly increased in the ST and FLSs of RA patients. TNF-α or hypoxia induced GYS1 expression and glycogen synthesis in RA FLSs. GYS1 knockdown by shRNA decreased the expression of IL-1β, IL-6, CCL-2, MMP-1, and MMP-9 and proliferation and migration by increasing AMP-activated protein kinase (AMPK) activity in RA FLS. AMPK inhibitor or knockdown AMPK could reverse the inhibitory effect of GYS1 knockdown on the inflammatory response in RA FLSs; however, an AMPK agonist blocked RA FLS activity. We further determined that hypoxia-inducible factor-1α mediates TNF-α- or hypoxia-induced GYS1 expression and glycogen levels. Local joint depletion of GYS1 or intraperitoneal administration with an AMPK agonist ameliorated the severity of arthritis in rats with collagen-induced arthritis.ConclusionOur data demonstrate that GYS1-mediated glycogen accumulation contributes to FLS-mediated synovial inflammation in RA by blocking AMPK activation. In our knowledge, this is a first study linking glycogen metabolism to chronic inflammation. Inhibition of GYS1 might be a novel therapeutic strategy for chronic inflammatory arthritis, including RA.

Little is known about the critical care management of children with traumatic brain injury (TBI) in low middle income countries. We aimed to identify indicators of intensive care unit (ICU) treatments associated with favorable outcomes in Argentine children with severe TBI.We conducted a secondary analysis of data from patients previously enrolled in a prospective seven center study of children with severe TBI who were admitted to an ICU in one of the seven study centers. Severe TBI was defined by head AIS ≥ 3, head CT with traumatic lesion, and admission GCS < 9. Seven indicators of best practice TBI care were examined. The primary outcome was discharge Pediatric Cerebral Performance Category Scale [PCPC] and Pediatric Overall Performance category Scale [POPC]. We also examined variation in ICU care and in-patient mortality.Of the 117 children, 67% were male and 7.5 (4.3) years on average, 92% had isolated TBI. Hypotension (54%) was more common than hypoxia (28%) and clinical or radiographic signs of high intracranial pressure (ICP) were observed in 92%. Yet, ICP monitoring occurred in 60% and hyperosmolar therapy was used in only 36%. Adherence to indicators of best TBI practice ranged from 55.6% to 83.7% across the seven centers and adherence was associated with favorable discharge PCPC (aRR 0.98; 95% CI [0.96, 0.99]), and POPC (aRR 0.98; 95% CI [0.96, 0.99]). Compared to patients whose adherence rates were below 65%, patients whose adherence rates were higher between 75%-100% had better discharge PCPC (aRR 0.28; 95% CI [0.10, 0.83]) and POPC (aRR 0.32; 95% CI [0.15, 0.73]. Two indicators were associated with favorable discharge PCPC: Avoidance of hypoxia (aRR 0.46; 95% CI [0.23, 0.93]), and Nutrition started in 72 hours (aRR 0.45; 95% CI [0.21, 0.99]). Avoiding hypoxia was also associated with favorable discharge POPC (aRR 0.47; 95% CI [0.22, 0.99]).There is variation in Argentine ICU practice in the care of children with severe TBI. Second insults are common and hyperosmolar therapy use is uncommon. Adherence to best practice TBI care by avoiding hypoxia and providing timely nutrition were associated with significantly favorable discharge outcomes. Implementing strategies that prevent hypoxia and facilitate early nutrition in the ICUs are urgently needed to improve pediatric TBI outcomes.

Background: Unregulated cell proliferation or growth is a prominent characteristic of cancer. We have previously demonstrated that LMPs (cell membrane microparticles derived from apoptotic human CEM T lymphoma cells stimulated with actinomycin D) strongly suppress the proliferation of not only human endothelial cells but also mouse Lewis lung carcinoma cells. Methods: LMPs were generated either from CEM T cells using different stimuli or from 3 different types of lymphocytes. The effects of LMPs on cancer cell proliferation were examined using cell lines from different species and tissues. The cell cycle kinetics was evaluated by FACS and the expression of cell cycle-related genes was determined using quantitative RT-PCR. The in vivo anti-tumor effect of LMPs was investigated using xenografts and allografts. Results: LMPs at doses far above physiological levels dramatically suppressed the proliferation of cancer cells in a non species-specific manner. LMPs selectively target high proliferating cells and their anti-proliferative effect is not dependent on parental cell origin or stimuli. The anti-proliferative effect of LMPs was due to induction of cell-cycle arrest in G0/G1, with associated increases in expression of the cyclin-dependent kinase inhibitors p15INK4b, p16INK4a, and p21Cip1. In vivo, LMPs significantly suppressed tumor growth in animal tumor models. Conclusion: These results highlight the potential role of LMPs in modulating the growth of high proliferating cells. Given that cell-based therapies are considered less toxic than pharmacologic approaches and have the potential to target multiple pathways in a synergistic manner, LMPs may serve as a veritable option for cancer treatment.

There is little information on the type of early care provided to children with traumatic brain injury (TBI) in low middle income countries. We benchmarked early prehospital [PH] and emergency department [ED] pediatric TBI care in Argentina.We conducted a secondary analysis of data from patients previously enrolled in a prospective seven center study of children with TBI. Eligible participants were patients 0-18 years, and had diagnosis of TBI (admission Glasgow Coma scale score [GCS] < 13 or with GCS 14-15 and abnormal head CT scan within 48 hours of admission, and head AIS > 0). Outcomes were transport type, transport time, PH and ED adherence to best practice, and discharge Pediatric Cerebral Performance Category Scale (PCPC) and Pediatric Overall Performance category Scale (POPC).Of the 366 children, mean age was 8.7 (5.0) years, 58% were male, 90% had isolated TBI and 45.4% were transported by private vehicle. 50 (34.7%) of the 144 children with severe TBI (39.3% of all TBI patients) were transported by private vehicle. Most (267; 73%) patients received initial TBI care at an index hospital prior to study center admission, including children with severe (81.9%) TBI. Transport times were shorter for those patients who were directly transported by ambulance to study center than for the whole cohort (1.4 vs.5.5 hours). Ambulance blood pressure data were recorded in 30.9%. ED guideline adherence rate was higher than PH guideline adherence rate (84.8% vs. 26.4%). For patients directly transferred from scene to study trauma centers, longer transport time was associated with worse discharge outcome (PCPC aOR 1.10 [1.04, 1.18] and (POPC aOR 1.10 [1.04, 1.18]). There was no relationship between PH or ED TBI guideline adherence rate and discharge POPC and PCPC.This study benchmarks early pediatric TBI care in Argentina and shows that many critically injured children with TBI do not receive timely or best practice PH care, that PH guideline adherence rate is low and that longer transport time was associated with poor discharge outcomes for patients with direct transfer status. There is an urgent need to improve the early care of children with TBI in Argentina, especially timely transportation to a hospital.

BACKGROUND: Hepatitis B virus (HBV) infection is a significant clinical and financial burden for chronic hepatitis B (CHB) patients. In Beijing, China, partial reimbursement on antiviral agents was first implemented for the treatment of CHB patients in July 1, 2011. AIMS: In this study, we describe the medical cost and utilization rates of antiviral therapy for CHB patients to explore the impact of the new partial reimbursement policy on the medical care cost, the composition, and antivirals utilization. METHODS: Clinical and claims data of a retrospective cohort of 92,776 outpatients and 2,774 inpatients with non-cirrhotic CHB were retrieved and analyzed from You'an Hospital, Beijing between February 14, 2008 and December 31, 2012. The propensity score matching was used to adjust factors associated with the annual total cost, including age, gender, medical insurance type and treatment indicator. RESULTS: Compared to patients who paid out-of-pocket, medical cost, especially antiviral costs increased greater among patients with medical insurance after July 1, 2011, the start date of reimbursement policy. Outpatients with medical insurance had 16% more antiviral utilization; usage increased 3% among those who paid out-of-pocket after the new partial reimbursement policy was implemented. CONCLUSIONS: Direct medical costs and antiviral utilization rates of CHB patients with medical insurance were higher than those from paid out-of-pocket payments, even after adjusting for inflation and other factors. Thus, a new partial reimbursement program may positively optimize the cost and standardization of antiviral treatment.

This paper focuses on an adaptive dynamic surface control based on the Radial Basis Function Neural Network for a fourth-order permanent magnet synchronous motor system wherein the unknown parameters, disturbances, chaos, and uncertain time delays are presented. Neural Network systems are used to approximate the nonlinearities and an adaptive law is employed to estimate accurate parameters. Then, a simple and effective controller has been obtained by introducing dynamic surface control technique on the basis of first-order filters. Asymptotically tracking stability in the sense of uniformly ultimate boundedness is achieved in a short time. Finally, the performance of the proposed control has been illustrated through simulation results.

A recent genome-wide association study has identified a new susceptibility locus, kinesin family member 1B gene (KIF1B), strongly associated with progression from chronic hepatitis B (CHB) to hepatitis B virus-related hepatocellular carcinoma (HCC) in Chinese population, this study was carried out to explore the role of the genetic variants in KIF1B in the development of chronic hepatitis B.Three KIF1B polymorphisms (rs8019, rs17401924, and rs17401966) were selected and genotyped in 473 CHB patients and 580 controls with no history of CHB. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression model. None of these three SNPs showed association with CHBs after adjusting for age and gender. Equivalence-based method analysis confirmed the absence of association. In the further haplotype analysis, three common haplotypes were observed in this study population, but no significant effect was also found for haplotypes in the progression to CHB.This study showed the new locus identified for HCC, KIF1B, was not associated with progression to CHB, implying distinct genetic susceptibility factor contributes to the progression from hepatitis B virus infection to HCC. Nevertheless, further comprehensive analyses are warranted to dissect the mechanism.

Abstract Background There are three childhood disruptive behavior disorders (DBDs), attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD). The most common comorbid disorder in ADHD is ODD. DSM-IV describes three ADHD subtypes: predominantly inattentive type (ADHD-IA), predominantly hyperactive-impulsive type (ADHD-HI), and combined type (ADHD-C). Prior work suggests that specific candidate genes are associated with specific subtypes of ADHD in China. Our previous association studies between ADHD and functional polymorphisms of COMT and MAOA, consistently showed the low transcriptional activity alleles were preferentially transmitted to ADHD-IA boys. Thus, the goal of the present study is to test the hypothesis that COMT Val158Met and MAOA-uVNTR jointly contribute to the ODD phenotype among Chinese ADHD boys. Methods 171 Chinese boys between 6 and 17.5 years old (mean = 10.3, SD = 2.6) with complete COMT val158met and MAOA-uVNTR genotyping information were studied. We used logistic regression with genotypes as independent variables and the binary phenotype as the dependent variable. We used p < 0.05 as the level of nominal statistical significance. Bonferroni correction procedures were used to adjust for multiple comparisons. Results Our results highlight the potential etiologic role of COMT in the ADHD with comorbid ODD and its predominately inattentive type in male Chinese subjects. ADHD with comorbid ODD was associated with homozygosity of the high-activity Val allele, while the predominantly inattentive ADHD subtype was associated with the low-activity Met allele. We found no evidence of association between the MAOA-uVNTR variant and ADHD with comorbid ODD or the ADHD-IA subtype. Conclusion Our study of attention deficit hyperactivity disorder comorbid oppositional defiant disorder and its predominately inattentive type highlights the potential etiologic role of COMT for ADHD children in China. But we failed to observe an interaction between COMT and MAOA, which suggests that epistasis between COMT and MAOA genes does not influence the phenotype of ADHD-IA with comorbid ODD in a clinical sample of Chinese male subjects. To confirm our findings further studies with a larger number of subjects and healthy controls are needed.