BACKGROUND: Myocardial ischemia-reperfusion (I/R) is a serious and irreversible injury. Bone marrow-derived mesenchymal stem cells (MSCs) is considered to be a potential therapy for I/R injury due to the paracrine effects. High-mobility group box 1 (HMGB1) is a novel mediator in MSC and regulates the response of inflammation injury. Signal Transduction and Transcription Activator 3 (STAT3) is a critical transcription factor and important for release of paracrine factors. However, the relationship between HMGB1 and STAT3 in paracrine effect of MSC remains unknown. METHODS: In vitro, hypoxia/reoxygenation injury model was established by AnaeroPack System and examined by Annexin V flow cytometry, CCK8 assay and morphology observation. Detection of apoptotic proteins and protein expression of HMGB1 and STAT3 by Western blot. RESULTS: The conditioned medium of MSCs with or without LPS pretreatment was cocultured with H9C2 cells for 24 h before hypoxia treatment and MSC showed obvious cardiomyocytes protect role, as evidence by decreased apoptosis rate and improved cells viability, and LPS pretreated MSC exhibited better protect role than untreated MSC. However, such effect was abolished in HMGB1 deficiency group, silencing HMGB1 decreased the secretion of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin growth factor (IGF), cell viability, and the expression of STAT3. Furthermore, STAT3 silence attenuated the protective effect of LPS in MSC. CONCLUSIONS These findings suggested that LPS improved MSC-mediated cardiomyocytes protection by HMGB1/STAT3 signaling.

OBJECTIVES: To find the appropriate method for age estimation for different ages and sexes. METHODS: The costal cartilage, sternum and pubic symphysis of 91 unknowns from 2000 to 2020 from the Forensic Department of the Criminal Investigation Team of Shanghai Public Security Bureau were collected. Costal cartilage, sternal and pubic symphysis inferences were used to estimate the age, and the consistency between the estimated results and the actual physiological age of the unknowns was tested. The accuracy of age estimation of different samples was compared, and the relationship between accuracy and age and sex was analyzed. RESULTS: Using the costal cartilage method, the inference errors of males, females and the whole population under 40 years old were (0.608±2.298) years, (0.429±1.867) years and (0.493±2.040) years, while those over 40 years old were (-1.707±3.770) years, (-3.286±4.078) years and (-2.625±4.029) years. The differences between different age groups in these three populations were statistically significant (P<0.05). Using the sternum method, the inference errors of males and females under the age of 40 were (0.921±3.019) years and (0.452±1.451) years, while those over the age of 40 were (-5.903±5.088) years and (-1.429±2.227) years. The differences between different age groups in males and females were statistically significant (P<0.05). Using the pubic symphysis method, the inference errors of males and females under 40 years old were (-0.204±1.876) years and (0.238±2.477) years, while those over 40 years old were (1.500±2.156) years and (-2.643±4.270) years. The differences between different age groups in males and females were statistically significant (P<0.05). Using the sternum method and pubic symphysis method for age estimation of over 40 years old, the difference between different sexes was statistically significant (P<0.05). CONCLUSIONS All three methods of age estimation are stable and effective and more accurate for people under 40 years old. For age estimation of unknowns over 40 years old, the pubic symphysis method is preferred in males and the sternum method is preferred in females.
Adult ; Age Determination by Skeleton/methods* ; Child, Preschool ; China ; Female ; Forensic Anthropology/methods* ; Forensic Medicine ; Humans ; Infant ; Male ; Pubic Symphysis/anatomy & histology*

Objective To systematically analyze the framework and core content of physical activity inclusive school health policies. Methods This study conducted systematic content analysis of key messages of WHO key documents related to physical activity and school health services, and constructed policy and research framework. WHO's key policy documents in the field of school health included: Making Every School a Health-Promoting School Implementation Guidelines, WHO Guidelines on School Health Services, and the Global Criteria and Indicators for Making Every School a Health-Promoting School, and the key documents in the field of physical activity mainly include Global Action Plan for Physical Activity Promotion 2018-2030: Strengthening Physical Activity for a Healthy World, and WHO Guidelines on Physical Activity and Sedentary Behavior (Children and adolescents). Results Physical activity, as a health strategy and development strategy, is one of the most important tools for achieving health-promoting schools. In the area of health and education, the key to building health-promoting schools is to focus on child functioning and development, with the goal of promoting healthy inclusion and equity in schools. In the school setting, physical activity for children and adolescents is integrated into the school health service continuum with a focus on health promotion. At the macro level, the state and relevant authorities should establish a strategic structure and strategic planning for the integration of physical activity into the school health service system. At the meso level, educational institutions should develop and improve school health service policies and programs, and improve school health service tools based on the requirements of WHO school health service guidelines. Child health services are achieved through the provision of high-quality physical education programs and after-school physical activities. At the micro level, guided by global standards for building health-promoting schools, physical activity is promoted in the form of lessons and activities for healthy child development. Integrating physical activity into the school health service system can be done in six areas: school health leadership and governance, school infrastructure funding, school health service delivery that supports physical activity, human resources for school health, school health-related medicine and technology, and school health information system. We need to implement health-promoting school policies, strengthen multi-level school leadership and governance, raise the necessary funds to develop human resources adapted to the construction of health-promoting schools and build programs to support physical activity. Conclusion School health service is an important area for promoting children's health and achieving the UN 2030 Sustainable Development Goals, and physical activity is an important strategy of school health services. Policy documents issued by WHO construct the integration of physical activity into the policy framework of the school health service system, of which the core component is to integrate physical activity into the health-promoting school with educational and physical activity approaches. According to the WHO six building blocks of health service system, the integration of physical activity into the school health requires strengthening school health leadership and governance, improving school infrastructure financing, developing school health human resources, developing school-based health-related medical technologies, and establishing a health information system for sharing student health data.

Objective To explore the theories, content and approaches of integrating physical activity in children's eye health service system in the context of health services. Methods From the perspectives of six building blocks of WHO health system, namely, leadership and governance, financing, human resources for health, service delivery, medical technology, and health information system, we analyzed the policy framework and key contents related to school-based eye health and physical activity, and explored how to promote the implementation of physical activity into the school-based eye health service system, and the integration of physical activity into the eye health continuum: prevention, intervention, rehabilitation, and health promotion. Results In perspective of health system, the integration of physical activity into school-based eye health services should be in accordance with the five principles of cross-cutting health services, namely, universal accessibility and equity, human rights, evidence-based, life-span, and empowerment. According to the World Vision Report, WHO advocates to build a person-centered eye health service system, and person-centeredness is the core concept of the new model of school-based eye health services and physical activity integration. WHO advocates a school-based approach to education and physical activity in health-promoting schools to promote student health, physical activity as a preventive, interventional, rehabilitation and health promotive measure related to children's eye health, and vigorously train professionals within schools who have knowledge and skills related to physical activity and eye health, build an information system on physical activity and children's eye health, and promote the integration of physical activity into the school-based eye health service system. Conclusion Physical activity is an important measure to promote children's eye health and an important component to achieve a person-centered eye health service system. Based on the six building blocks of the WHO health service system, a school-based eye health service that integrates a theoretical and methodological system of physical activity is constructed, requiring the provision of health promotion methods such as education and physical activity in the school setting, to enhance leadership and governance of eye health services based on educational and physical activity approaches in the school setting, establish new funding mechanisms, provide financial security, develop human resources related to physical activity for eye health, improve related service delivery systems, develop high-quality physical activity intervention eye health techniques and equipment, and integrate information on children's physical activity and eye health into school health information systems to achieve children's eye health and promote their physical and mental development.

Objective To analyze the overall functioning of children with learning disabilities, and develop individualized exercise rehabilitation protocol using International Classification of Functioning, Disability and Health (ICF). Methods Based on the theoretical framework of ICF and the disease diagnosis of International Classification of Diseases (ICD-11), and with the perspective of child development, the functional profiles of cognition, understanding, attention, thinking, motor, and activity and participation of children with learning disabilities were analyzed. A function-oriented and individulized exercise rehabilitation protocol for children with learning disabilities was constructed in light of ICF bio-psycho-social health paradignm and the theory of somatic and mental interaction. Results The functional performance of children with learning disabilities mainly demonstrated in mental dysfunction in physical functioning in the activities and participation limitations, such as learning and applying knowledge, general tasks and demands, and communication. For the environment factors, products and technology for education, products and technology for culture, recreation and sports, and services, systems and policies could also affect children with learning disabilities. Physical activity was beneficial for children with learning disabilities to improve mental and motor functioning and to effectively enhance intellectual, cognitive, attentional, communication, and mobility skills for the overall development of the children. Physical activity for children with learning disabilities was selected according to WHO guidelines for physical activity and sedentary behavior for children, and moderate to vigorous physical activity for at least 60 minutes, as well as high-intensity training no less than three times a week, together with appropriate physical games and leisure physical activities could effectively improve learning outcomes and reduce learning disabilities. Conclusion The health condition, functioning and motor development of children with learning disability had been analyzed using ICD-11 and ICF, and with the theories of somatic and metal interaction and ICF bio-psycho-social model, the holistic and function-oriented exercise rehabilitation program was developed that recommended at least 60 minutes of moderate intensity physical activity, including aerobic exercise and physical games, per day, and at least three times a week of high intensity physical activity of no less than 30 minutes, including plyometrics and physical competition. The development of individualized function-based exercise rehabilitation programs incorporating the learning disability and motor function characteristics of children could effectively improve the cognitive, attentional, and thinking functions of children with learning disabilities, reduce learning disabilities, and promote the overall development of children.

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.

Purpose: This study aimed to investigate the potential systemic antitumor effects of stereotactic ablativeradiotherapy (SABR) and apatinib (a novel vascular endothelial growth factor receptor2 inhibitor) via reversing the immunosuppressive tumor microenvironment for lung carcinoma. Materials and Methods: Lewis lung cancer cells were injected into C57BL/6 mice in the left hindlimb (primary tumor;irradiated) and in the right flank (secondary tumor; nonirradiated). When both tumors grewto the touchable size, mice were randomly divided into eight treatment groups. These groupsreceived normal saline or three distinct doses of apatinib (50 mg/kg, 150 mg/kg, and 200mg/kg) daily for 7 days, in combination with a single dose of 15 Gy radiotherapy or not tothe primary tumor. The further tumor growth/regression of mice were followed andobserved. Results: For the single 15 Gy modality, tumor growth delay could only be observed at the primarytumor. When combining SABR and apatinib 200 mg/kg, significant retardation of both primaryand secondary tumor growth could be observed, indicated an abscopal effect wasinduced. Mechanism analysis suggested that programmed death-ligand 1 expressionincreased with SABR was counteract by additional apatinib therapy. Furthermore, whenapatinib was combined with SABR, the composition of immune cells could be changed.More importantly, this two-pronged approach evoked tumor antigen–specific immune responsesand the mice were resistant to another tumor rechallenge, finally, long-term survivalwas improved. Conclusion Our results suggested that the tumor microenvironment could be managed with apatinib,which was effective in eliciting an abscopal effect induced by SABR.

Objective To evaluate the effectiveness of perioperative fasting abbreviation in traumatic patients undergoing selective surgeries.Methods The traumatic patients undergoing selective surgeries from November 2016 to January 2017 at our department were selected for this prospective cohort study.They were divided into an intervention group (69 patients) and a control group (121 patients) according to the wards where they stayed.The intervention group was fasted for solids 6 hours prior to surgery and received oral solution with maltodextrin 2 hours prior to surgery.After surgery,they were allowed to drink liquids as soon as they were awakened.Normal food was allowed 2 hours later.The control group was fasted for either liquids or solids the night before surgery.After surgery,the patients who had received brachial plexus block only were allowed liquids with no limitation while the other patients were allowed liquids 6 hours after surgery and then were free for solids and liquids if no discomfort was observed.The time periods for preoperative liquids and solids fasting and for postoperative intake of liquids and solids were recorded and compared between the 2 groups.The perioperative well-beings (including anxiety,thirst,hunger,nausea,fatigue,dizziness,sweating and stomach discomfort) and serum glucose levels were compared between the 2 groups.Adverse reactions were observed.Results The preoperative fasting time for liquids for the intervention group (4.5 ± 2.9 hours) was significantly shorter than that for the control group (14.3 ±3.9 hours) (P ＜ 0.05).The preoperative fasting time for solids for the intervention group (17.6 ± 3.0 hours) were significantly longer than that for the control group (16.1 ±3.8 hours) (P ＜ 0.05).The postoperative fasting time periods for both liquids [1 (0,3) h] and solids [2 (1,4) h] for the intervention group were significantly shorter than those for the control group [6(6,6) h] hours and [6(6,6) h] (P ＜ 0.05).Compared with the control group,the perioperative anxiety,thirst,hunger,nausea,fatigue,dizziness and stomach discomfort were significantly improved in the intervention group (P ＜ 0.05).The average serum glucose level was similar in both groups upon admission (P ＜ 0.05);it was significantly higher in the intervention group immediately before surgery (P ＜ 0.05) but was gradually decreased after surgery until there was no significant difference between the 2 groups (P ＞ 0.05).No major adverse reaction was observed in either group.Conclusion The protocol of perioperative fasting abbreviation may be safe and feasible in traumatic patients for selective surgeries,showing benefits of decreased anxiety,thirst,hunger,nausea,fatigue,dizziness and stomach discomfort.

OBJECTIVE: MicroRNAs (miRs) are attractive molecules to be considered as one of the blood-based biomarkers for neurodegenerative disorders such as Alzheimer's disease (AD). The goal of this study was to explore their potential value as biomarkers for the diagnosis of AD. METHODS: The expression levels of exosomal miR-135a, -193b, and -384 in the serum from mild cognitive impairment (MCI), dementia of Alzheimer-type (DAT), Parkinson's disease with dementia (PDD), and vascular dementia (VaD) patients were measured with a real-time quantitative reverse transcriptase PCR (qRT-PCR) method. RESULTS: Both serum exosome miR-135a and miR-384 were up-regulated while miR-193b was down-regulated in serum of AD patients compared with that of normal controls. Exosome miR-384 was the best among the three miRs to discriminate AD, VaD, and PDD. Using the cut-off value could better interpret these laboratory test results than reference intervals in the AD diagnosis. ROC curve showed that the combination of miR-135a, -193b, and -384 was proved to be better than a particular one for early AD diagnosis. CONCLUSION Our results indicated that the exosomal miRs in the serum were not only potential biomarker of AD early diagnosis, but might also provide novel insights into the screen and prevention of the disease.
Aged ; Alzheimer Disease ; blood ; Biomarkers ; blood ; Case-Control Studies ; Cognitive Dysfunction ; blood ; Dementia, Vascular ; blood ; Diagnosis, Differential ; Early Diagnosis ; Exosomes ; metabolism ; Female ; Humans ; Male ; MicroRNAs ; blood ; Parkinson Disease ; blood ; Sensitivity and Specificity

Mitochondrial diseases are maternally inherited heterogeneous disorders that are primarily caused by mitochondrial DNA (mtDNA) mutations. Depending on the ratio of mutant to wild-type mtDNA, known as heteroplasmy, mitochondrial defects can result in a wide spectrum of clinical manifestations. Mitochondria-targeted endonucleases provide an alternative avenue for treating mitochondrial disorders via targeted destruction of the mutant mtDNA and induction of heteroplasmic shifting. Here, we generated mitochondrial disease patient-specific induced pluripotent stem cells (MiPSCs) that harbored a high proportion of m.3243A>G mtDNA mutations and caused mitochondrial encephalomyopathy and stroke-like episodes (MELAS). We engineered mitochondrial-targeted transcription activator-like effector nucleases (mitoTALENs) and successfully eliminated the m.3243A>G mutation in MiPSCs. Off-target mutagenesis was not detected in the targeted MiPSC clones. Utilizing a dual fluorescence iPSC reporter cell line expressing a 3243G mutant mtDNA sequence in the nuclear genome, mitoTALENs displayed a significantly limited ability to target the nuclear genome compared with nuclear-localized TALENs. Moreover, genetically rescued MiPSCs displayed normal mitochondrial respiration and energy production. Moreover, neuronal progenitor cells differentiated from the rescued MiPSCs also demonstrated normal metabolic profiles. Furthermore, we successfully achieved reduction in the human m.3243A>G mtDNA mutation in porcine oocytes via injection of mitoTALEN mRNA. Our study shows the great potential for using mitoTALENs for specific targeting of mutant mtDNA both in iPSCs and mammalian oocytes, which not only provides a new avenue for studying mitochondrial biology and disease but also suggests a potential therapeutic approach for the treatment of mitochondrial disease, as well as the prevention of germline transmission of mutant mtDNA.
Animals ; DNA, Mitochondrial ; genetics ; Humans ; Induced Pluripotent Stem Cells ; cytology ; metabolism ; MELAS Syndrome ; genetics ; Male ; Mice ; Microsatellite Repeats ; genetics ; Mitochondria ; genetics ; metabolism ; Mutation ; genetics