Innate immunity is the first line of defense against viral infection.Hepatitis E virus(HEV)infection usually cau-ses acute self-limiting diseases in immunocompetent patients,but results in chronic infection in immunocompromised patients or pregnant people.After HEV infects host cells,pattern recognition receptors(PRRs)recognize the viral genome,thus indu-cing rapid activation of multiple antiviral signal pathways in the host immune system,and the expression of interferons(IFNs)and interferon stimulated genes(ISGs),and consequently inhibiting viral replication.To escape host antiviral responses,HEV encoded proteins regulate host antiviral signal pathways and subsequently inhibit antiviral responses,such as those involving cytokines or chemokines.The regulation of host signal pathways by HEV infection and the escape of HEV from host innate im-munity are reviewed herein.

Aim To prepare prostate cancer exosomes containing melittin and observe their uptake by prostate cancer cells. Methods Cells treated with starvation for different time were screened for exosome extraction. Exosomes from PC-3 cells were extracted by ultracentrifugation, and the extracted particles were examined by transmission electron microscopy, nanoparticle tracking analyzer(NTA), and Western blot. Melittin exosome system was prepared by repeated freeze-thaw method, incubation at room temperature as well as electroporation, and the size of encapsulation efficiency was measured by centrifugation. A high-performance liquid chromatography(HPLC)method was applied to assay the content of melittin exosomes(exo-mel). Fluorescence inverted microscopy was employed to evaluate the uptake of melittin exosomes by PC-3 cells, DU145 cells as well as LNCaP cells. Results The results of starvation treatment showed that 24 h starvation treatment was the optimal time point. TEM results showed that the exosomes were round or oval in shape with a distinct membranous structure, and the diameter was around 100 nm. The reagent protein concentration for NTA analysis of exosomes was 0.222 g·L-1. The results of Western blot for the marker proteins of exosomes showed that Alix and CD63 were positively expressed, which indicated that the exosomes could be obtained by starvation culture of PC-3 cells and ultracentrifugation. The results of entrapment efficiency showed that the entrapment efficiency of electroporation method was 17.51% ± 2.39%, that of repeated freeze-thaw method was 11.46% ± 1.02%, and that of room temperature incubation method was 3.93% ± 2.44%. The encapsulation efficiency of electroporation was the highest with significant difference(P<0.05). The uptake assay showed that PC-3 cells could efficiently take up exo-mel in a time-dependent manner, and DU145 cells and LNCaP cells also could take up exo-mel over time. Conclusions Exosomes can be accessed by starvation treatment and high-speed centrifugation, and the prostate cancer melittin exosome system prepared by electroporation method could be taken up by prostate cancer cells.

OBJECTIVES: To study the safety and efficacy of dexmedetomidine hydrochloride combined with midazolam in fiberoptic bronchoscopy in children. METHODS: A total of 118 children who planned to undergo fiberoptic bronchoscopy from September 2018 to February 2021 were enrolled. They were divided into a control group ( RESULTS: Compared with the control group, the observation group had significantly decreased MAP at T CONCLUSIONS Dexmedetomidine hydrochloride combined with midazolam is a safe and effective way to administer general anesthesia for fiberoptic bronchoscopy in children, which can ensure stable vital signs during examination, reduce intraoperative adverse reactions and postoperative agitation, shorten examination time, and increase amnesic effect.
Bronchi ; Bronchoscopy ; Child ; Dexmedetomidine/adverse effects* ; Humans ; Hypnotics and Sedatives/adverse effects* ; Midazolam ; Prospective Studies

Objective To study and analyze the theory, policy framework, and core content of physical activity policies and physical activity guidelines. Methods Using a policy research and content analysis approach and the theory of the six components of World Health Organization (WHO) health service system, we specifically analyze the theory, framework, and core content of WHO Global Action Plan on Physical Activity and WHO Physical Activity Guidelines. Results The Global Plan of Action for Physical Activity 2018-2030 (Action Plan) is an international policy document on physical activity issued by WHO that incorporates physical activity within the context of the seven principles of human rights, the life span, evidence-based practice, proportional universality, policy coherence and integration of health into all policies, participation and empowerment, and multisectoral partnerships into health services and social development. The Action Plan consists of four strategic objectives and 20 policy actions, covering six areas of WHO health service system, and the integration of physical activity policies into health services is of great importance in promoting the achievement of the United Nations Sustainable Development Goal 3 of universal health coverage. As a technical document for the implementation of the Action Plan, 2020 WHO Guidelines on Physical Activity and Sedentary Behavior (Guidelines) adopted the PI/ECO approach to analyze the physical activity needs of various groups of people, and provide guidelines to increase physical activity and reduce sedentary behavior for children and adolescents, adults, older adults, pregnant and postpartum women, people with chronic diseases and people with disabilities. The guidelines cover duration, frequency, and intensity of physical activity, types of physical activity, critical and important health outcomes of physical activity, and health risk prevention and related considerations. The Guidelines implement the relevant guiding principles of the Action Plan and aim to improve overall population participation in physical activity at the micro level and improve critical and important health outcomes for the overall population. Conclusion As a health and development strategy, the Action Plan promotes the integration of physical activity into the health delivery system to facilitate the achievement of the United Nations 2030 Sustainable Development Goal 3 of universal health coverage.The four strategic objectives and 20 policy actions of the Action Plan can be integrated into these six areas based on the six components of WHO Health Service Delivery System: leadership and governance, financing, human resources, service delivery, medical technology, and health information. As a technical document to implement the Action Plan, the Guidelines are based on the PI/ECO approach framework and provide guidance on increasing physical activity and reducing sedentary behavior for children and adolescents, adults, older adults, pregnant and postpartum women, chronic patients, and persons with disabilities. The core content addresses the target populations, duration, frequency, and intensity of physical activity, types of physical activity, critical and important health outcomes of physical activity, and health risk prevention and related considerations.

Objective:To explore the theory and methods of integrating sports into modern health service systems. Methods:Based on the theory of World Health Organization modern health service systems and the policy guideline Rehabilitation in Health Service Systems, we analyzed how to promote the integration of sports into modern health service systems in six areas: leadership and governance capacity, financing, health human resources, service delivery, medical technology and health information systems, systematically analyzed the key elements and requirements for integrating physical education and sports into the health service system in the four segments of the health service continuum: prevention, intervention, rehabilitation and health promotion. Results:The goal of building a human-centered, cross-sectoral and multidisciplinary health service system was proposed, requiring the promotion of the integration of medicine and sports, the use of sports intervention as a method of health intervention, the development of service technologies and standards for the integration of sports and health; the training of professionals who master sports intervention and sports rehabilitation, and the development of information systems to promote the development of the integration of sports and health services. Conclusion:Sports is an important mean of health and an important part of modern health services. Starting from the components of the health service system, we can build a theoretical and methodological system for integrating sports into the modern health service system, so as to promote the realization of a health service system covering the whole population and the whole life cycle, achieve the United Nations 2030 Sustainable Development Goal 3: ensure healthy lives and promote well-being for all at all ages; and realize the goals related to "Healthy China".

OBJECTIVE: To investigate the clinical features and outcome of neonatal acute respiratory distress syndrome (ARDS) in southwest Hubei, China. METHODS: According to the Montreux definition of neonatal ARDS, a retrospective clinical epidemiological investigation was performed on the medical data of neonates with ARDS who were admitted to Department of Neonatology/Pediatrics in 17 level 2 or level 3 hospitals in southwest Hubei from January to December, 2017. RESULTS: A total of 7 150 neonates were admitted to the 17 hospitals in southwest Hubei during 2017 and 66 (0.92%) were diagnosed with ARDS. Among the 66 neonates with ARDS, 23 (35%) had mild ARDS, 28 (42%) had moderate ARDS, and 15 (23%) had severe ARDS. The main primary diseases for neonatal ARDS were perinatal asphyxia in 23 neonates (35%), pneumonia in 18 neonates (27%), sepsis in 12 neonates (18%), and meconium aspiration syndrome in 10 neonates (15%). Among the 66 neonates with ARDS, 10 neonates (15%) were born to the mothers with an age of ≥35 years, 30 neonates (45%) suffered from intrauterine distress, 32 neonates (49%) had a 1-minute Apgar score of 0 to 7 points, 24 neonates (36%) had abnormal fetal heart monitoring results, and 21 neonates (32%) experienced meconium staining of amniotic fluid. Intraventricular hemorrhage was the most common comorbidity (12 neonates), followed by neonatal shock (9 neonates) and patent ductus arteriosus (8 neonates). All 66 neonates with ARDS were treated with mechanical ventilation in addition to the treatment for primary diseases. Among the 66 neonates with ARDS, 10 died, with a mortality rate of 15% (10/66), and 56 neonates were improved or cured, with a survival rate of 85% (56/66). CONCLUSIONS Neonatal ARDS in southwest Hubei is mostly mild or moderate. Perinatal asphyxia and infection may be the main causes of neonatal ARDS in this area. Intraventricular hemorrhage is the most common comorbidity. Neonates with ARDS tend to have a high survival rate after multimodality treatment.
China ; Female ; Humans ; Infant, Newborn ; Meconium Aspiration Syndrome ; Pregnancy ; Respiratory Distress Syndrome, Newborn ; Retrospective Studies

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

OBJECTIVE To establish a platform of electrophysiology using vagal ganglion neurons (VGNs) isolated from adult canines. METHODS The VGNs were enzymatically isolated from adult canines of either gender and cultured under experimental conditions. Action potential (AP), repetitive firing, voltage-gated outward K+ currents (IK) and hyperpolarization-mediated inward currents (Ih) were recorded under current-and voltage-clamp configurations before and after treatment. RESULTS Analysis of AP waveform showed that ① inaddition to traditionally classified myelinated A- and unmyelinated C-types, myelinated Ah-types could also be identified in females rather than in males; ② step current depolarization evoked a stimulus intensity-dependent repetitive discharge, and to reach a similar firing frequency, the lowest stimulus intensity was required for A-types, a similar or slightly higher stimulus intensity was needed for Ah-types, and the highest stimulus intensity was required for C-types;③tetro?dotoxin significantly reduced the rate of depolarization and positively shifted the AP firing threshold of Ah-types, and iberiotoxin dramatically increased the neuroexcitability of Ah-types;④all tested neurons functionally expressed IK and Ih, and the current density for both channels on average was A-types>Ah-types>C-types; ⑤ although the distribution of afferent types of VGNs differed between males and females, the known difference in discharge profiles of A- and C-types isolated from male and female rats was not studied here. CONCLUSION The VGNs can be successfully isolated from adult canines, AP, IK and Ih can be recorded. The tight seal can be held for at least 30 min, which may be enough for pharmacological investigation.

Fenofibrate, an agonist for peroxisome proliferator-activated receptor alpha (PPAR-α), lowers blood pressure, but whether this action is mediated via baroreflex afferents has not been elucidated. In this study, the distribution of PPAR-α and PPAR-γ was assessed in the nodose ganglion (NG) and the nucleus of the solitary tract (NTS). Hypertension induced by drinking high fructose (HFD) was reduced, along with complete restoration of impaired baroreceptor sensitivity, by chronic treatment with fenofibrate. The molecular data also showed that both PPAR-α and PPAR-γ were dramatically up-regulated in the NG and NTS of the HFD group. Expression of the downstream signaling molecule of PPAR-α, the mitochondrial uncoupling protein 2 (UCP2), was up-regulated in the baroreflex afferent pathway under similar experimental conditions, along with amelioration of reduced superoxide dismutase activity and increased superoxide in HFD rats. These results suggest that chronic treatment with fenofibrate plays a crucial role in the neural control of blood pressure by improving baroreflex afferent function due at least partially to PPAR-mediated up-regulation of UCP2 expression and reduction of oxidative stress.
Afferent Pathways ; drug effects ; Animals ; Antihypertensive Agents ; pharmacology ; Baroreflex ; drug effects ; Blood Pressure ; drug effects ; Fenofibrate ; pharmacology ; Male ; Oxidative Stress ; drug effects ; PPAR gamma ; drug effects ; metabolism ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Transcriptional Activation ; drug effects ; Uncoupling Protein 2 ; drug effects ; metabolism ; Up-Regulation

AIM To study the chemical constituents from the twigs and leaves of Cryptomeria fortunei Hooibrenk ex Otto et Dietr.METHODS The ethyl acetate fraction of 95％ ethanol extract from C.fortunei was isolated and purified by silica,MCI,and Sephadex LH-20 column,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Eleven compounds were isolated and identified as isopimaric acid (1),sandaracopimaric acid (2),acetylisocupressic acid (3),imbricataloic acid (4),isocupressic acid (5),pinifolic acid (6),13-epicupressic acid (7),19-acetylagathadiol (8),agatadiol (9),phytol (10),elemol (11).CONCLUSION Compounds 1-10 are identified as diterpenoids and compound 11 is identified as sesquiterpenoid;Compounds 2,3,6-11 are obtained from this plant for the first time.