SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Animals ; COVID-19/genetics* ; Macaca mulatta ; SARS-CoV-2/genetics* ; Transcriptome

COVID-19/genetics* ; Genome, Viral/genetics* ; Humans ; RNA, Viral/genetics* ; RNA-Seq ; SARS-CoV-2/genetics* ; Whole Genome Sequencing

Objective:To evaluate our novel path based on anatomical division of the anterior lateral wall of calcaneus and the sustentaculum tali for precise sustentacular screw placement in the surgical treatment of calcaneal fractures of Sanders types Ⅱ and Ⅲ.Methods:The anterior lateral wall of the calcaneus was divided into the anterior-superior zone S 1, the anterior-inferior zone S 2, the posterior-superior zone S 3 and the posterior-inferior zone S 4 for demarcation of the screw insertion points by our method of Four Zones, and into the front, middle and rear sections by our method of Three Sections for demarcation of the screw target points. The specimens were scanned by CT and modeled by Mimics. On the 3D virtual model of the calcaneus, one screw was placed from each zone of the anterior lateral wall of the calcaneus to the sustentaculum tali body. The screw placement target for S 1 and S 2 was the medial intersection point P 1 of the front and middle sections of the sustentaculum tali, and that for S 3 and S 4 was the medial intersection point P 2 of the middle and rear sections of the sustentaculum tali. It was observed whether the screws were placed in the bone channel. A total of 72 patients were included who had been admitted to Department of Orthopaedics, Suqian Hospital Affiliated to Xuzhou Medical University for calcaneal fractures of Sanders types Ⅱ and Ⅲ from January 2017 to January 2021. They were divided into an anatomical division group and a 3D printing group according to their screw placement method for the sustentaculum tali. In the anatomical division group of 32 patients subjected to screw placement based on our anatomical division, there were 25 males and 7 females, aged from 24 to 60 years; in the 3D printing group of 40 patients subjected to screw placement assisted by 3D printing, there were 31 males and 9 females, aged from 25 to 58 years. The disparities between the parameters of sustentacular screw placement and the actual values were compared in the anatomical division group, and the total number of screws, screws on average, distribution of screws, and accuracy of screw placement were compared between the 2 groups. Results:All the screws which were virtually placed in the specimens of the calcaneus from S 1 and S 2 to P 1 and from S 3 and S 4 to P 2 passed through the bony channel, with no perforation into the tarsal sinus. There was no significant difference in the general date between the anatomical division group and the 3D printing group, showing they were comparable ( P > 0.05). In the anatomical division group, a total of 52 screws were placed to the sustentaculum tali with an average of (1.63 ± 0.48) screws per patient, and 2 screws were placed in 20 patients, yielding an accuracy rate of screw placement of 92.3% (48/52). There were no statistically significant differences between the parameters and the actual values of screw placement in the anatomical division group ( P > 0.05). In the 3D printing group, a total of 63 screws were placed to the sustentaculum tali with an average of (1.58 ± 0.49) screws per patient, and 2 screws were placed in 23 patients, yielding an accuracy rate of screw placement of 93.7% (59/63). There were no significant differences in the above comparisons between the anatomical division group and the 3D printing group ( P > 0.05). Conclusion:In the surgical treatment of calcaneal fractures of Sanders types Ⅱ and Ⅲ, the sustentacular screw placement based on our anatomical division of the anterior lateral wall of the calcaneus and the sustentaculum tali can lead to similar clinical accuracy as 3D printing-assisted screw placement does.

Objective:To investigate the care needs and influencing factors for caregivers of children with disabilities. Methods:From December, 2019 to January, 2020, and August to September, 2020, a total of 496 family caregivers of children with disabilities were surveyed in Shanghai. The Care Needs Assessment Tool for Children with Disabilities was used to measure the care needs rates and satisfaction, and multiple linear regression was performed to analyze the related factors. Results:The rate of total need was 71.8%, which was high in the information support (83.7%), spiritual support (75.9%) and financial support (74.1%), and was at an intermediate level in alternative service support (62.9%) and professional support (62.2%). The satisfaction of total need was 39.4%, which was at a intermediate level in the spiritual support (50.8%) and professional support (45.5%), and was at a low level in alternative service support (32.8%), financial support (32.3%) and information support (30.3%). The caregivers needed less support for thoses with higher public policy satisfaction (B = -3.252, 95%CI -5.370 to -1.134, P = 0.003) and the children with vision and speech disability, and undetermined disability (B_{vision disability}= -12.160, 95%CI -21.976 to -2.344, P = 0.015; B_{speech disability}= -12.754, 95%CI -22.583 to -2.925, P = 0.011; B_{undetermined disability}= -16.553, 95%CI -24.714 to -8.392, P < 0.001), while mothers (B = 9.071, 95%CI 4.293 to 13.848, P < 0.001) needed more support than grandparents. The caregivers with higher public policy satisfaction (B = 7.392, 95%CI 5.523 to 9.262, P < 0.001), the children with vision disability, hearing disability and speech disability (B_{vision disability}= 8.612, 95%CI 0.081 to 17.144, P = 0.048; B_{hearing disability}= 8.686, 95%CI 1.920 to 15.451, P=0.012; B_{speech disability}= 9.515, 95%CI 1.184 to 17.846, P = 0.025), lower barriers to social inclusion (B = 1.932, 95%CI 0.457 to 3.408, P = 0.010) and shorter average daily care hours (B = -4.123, 95%CI -6.247 to -1.999, P < 0.001) were more satisfactory for support. Conclusion:The care needs of children with disabilities are diverse, with the highest rate of need for information support and the lowest level of satisfaction. There is some variation in the care needs of children with different types of disabilities, family roles, average daily care hours and social environment characteristics.

Objective:To explore the nutritional status and influencing factors among children with disabilities in developed areas. Methods:From December, 2019 to January, 2020, and August to September, 2020, a total of 480 caregivers of children with disabilities aged two to 18 years in Shanghai were investigated their heights and weights, and the body mass index (BMI) was calculated. The influencing factors were analyzed from the dimensions of children's personal, family and social characteristics based on the Ecological System Theory. Chi-square test and binary Logistic regression model were used to analyze the influencing factors associated with the nutritional status of children with disabilities. Results:The prevalence of thinness, overweight and obesity in 480 children was 23.75%, 13.54% and 13.33%, respectively. Multivariate Logistic regression analysis showed that potato intake (OR = 0.420, 95%CI 0.197 to 0.893, P < 0.05) and caregivers' perception of child's weight (OR _underweight = 4.188, 95%CI 1.488 to 11.787, P < 0.01) were associated with children's thinness. Types of disability (OR _autism= 0.142, 95%CI 0.034 to 0.591, P < 0.01), the role of caregiver (OR _father= 5.519, 95%CI 1.110 to 27.440, P < 0.05), and caregivers' perception of the child's weight (OR _overweight = 5.669, 95%CI 1.112 to 28.903, P < 0.05) were associated with children's overweight/obesity. Conclusion:The prevalence of malnutrition among children with disabilities in Shanghai is higher than those typically-developing, especially thinness and obesity. The nutritional status is greatly affected by the type of disability, dietary intake and family characteristics.

Objective:To explore the quality of life of caregivers of children with disabilities and its influencing factors. Methods:From December, 2019 to January, 2020, and August to September, 2020, a total of 496 family caregivers of children with disabilities were surveyed in Shanghai. The 12-item Short-form Health Survey (SF-12) was used to measure the quality of life of 496 caregivers, and multiple linear regression was performed to analyze the related factors. Results:The score of physical component summary (PCS) of caregivers was (51.67±8.11), and the score of mental component summary (MCS) was (42.10±12.66). The scores of PCS were lower in caregivers with children aged 6 to 18 years (B = -1.783, 95%CI -3.279 to -0.287, P = 0.020), children with emotional instability (B = 2.719, 95%CI 1.254 to 4.184, P < 0.001), female caregivers (B = -3.765, 95%CI -6.578 to -0.953, P = 0.009), and caregivers who were relatively dissatisfied with the policy (B = 1.973, 95%CI 0.367 to 3.578, P = 0.016); and were higher in caregivers with children with speech disabilities (B = 3.463, 95%CI 0.053 to 6.873, P = 0.047). The types of disabilities of children (B_hearing = 9.465, 95%CI 5.107 to 13.823, P < 0.001; B_undetermined = 5.999, 95%CI 1.558 to 10.441, P = 0.008), playmates of children (B = 2.626, 95%CI 0.352 to 4.901, P = 0.024), education level of caregivers (B_{high middle school} = -4.701, 95%CI -8.028 to -1.374, P = 0.006; B_{high school} = -3.610, 95%CI -6.604 to -0.615, P = 0.018), family size (B = 2.616, 95%CI 0.479 to 4.753, P = 0.017) and per capita monthly income (B _{< 5000 Yuan}= -6.572, 95%CI -9.136 to -4.008, P < 0.001; B_{5000 to < 10000 Yuan} = -4.932, 95%CI -7.544 to -2.319, P < 0.001) were associated with the scores of MCS. Conclusion:The quality of life, especially the mental health, of caregivers of children with disabilities is poor. The influencing factors cover multiple dimensions such as caregivers, children, family and social environment.

Background: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. Methods: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. Results: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. Conclusion The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.

Background: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. Methods: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. Results: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. Conclusion The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.

Objective: To evaluate the 4-year clinical outcomes of patients following Firesorb bioresorbable scaffold (BRS) implantation. Methods: The study reported the 4-year follow-up results of the FUTURE I study. FUTURE I was a prospective, single-center, open-label, first-in-man study which evaluated the feasibility, preliminary safety, and efficacy of Firesorb stent in the treatment of coronary artery stenosis. A total of 45 patients with single de novo lesions in native coronary arteries ,who hospitalized in Fuwai Hospital from January to March 2016 were enrolled. After successfully stent implantation these patients were randomized in a 2∶1 ratio into cohort 1 (n=30) or cohort 2 (n=15). The patients in cohort 1 underwent angiographic, IVUS or OCT examination at 6 months and 2 years; and cohort 2 underwent angiographic, IVUS or OCT at 1 and 3 years. All patients underwent clinical follow-up at 1, 6 months and 1 year and annually thereafter up to 5 years. The primary endpoint was target lesion failure (TLF, including cardiac death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization). Secondary endpoints included patient-oriented composite endpoint (PoCE, defined as composite of all death, all miocardial infarction, or any revascularization). Results: A total of 45 patients were enrolled and implanted with Firesorb BRS, including 35 males (77.8%), and the age was (54.4±9.3) years. At 4 years, 10 patients in cohort 1 were reexamined by coronary angiography and OCT examination. Among them, 2 patients' stents were completely degraded and absorbed. Compared with the OCT images of the other 8 patients in cohort 2 at 3 years, the degree of stent degradation was increased, and no stent adherence was found. The 4-year clinical follow-up rate was 100%. In 4-year clinical following up, 2 patients suffered PoCE (4.4%): 1 patient underwent non-target vessel revascularization the day after index procedure and target vessel revascularization (Non-target lesion revascularization) at 2-year imaging follow-up; the other patient underwent target lesion revascularization during imaging follow-up at 4 years but not due to ischemic driven. There was no scaffold thrombosis or TLF events through 4 years. Conclusions: Four years after the implantation, complete degradation and absorption of the Firsorb stent are evidenced in some patients. Firesorb stent is feasible and effective in the treatment of patients with non-complex coronary lesions.
Absorbable Implants ; Cardiovascular Agents ; Coronary Artery Disease/surgery* ; Drug-Eluting Stents ; Humans ; Male ; Middle Aged ; Percutaneous Coronary Intervention ; Prospective Studies ; Sirolimus ; Treatment Outcome

Objective:To explore systematic implementation of World Health Organization Family International Classifications (WHO-FICs) in the field of rehabilitation: the theoretical and policy framework at macro level, governance and management mechanism at meso level, and implementation modules at micro levels, respectively. Methods:The policy and theoretical framework of rehabilitation development was discussed based on the international rehabilitation policy documents of WHO, mainly as World Report on Disability, Global Action Plan on Disability and Rehabilitation in Health Service System. Protocol and roadmap of systematic implementation of WHO-FICs, including International Classification of Diseases (ICD-11), International Classification of Functioning, Disability and Health (ICF), and International Classification of Health Intervention (ICHIβ-2) was proposed. Results:With the use of WHO-FICs, the theoretical and policy framework of rehabilitation was constructed, and the contents and principles of modern rehabilitation services were clarified at macro-level. Rehabilitation is an important part of health service, there are six building blocks: i.e. leadership and governance, financing, human resources for health, service providing, medical technology and health information system. It proposed to use knowledge management system of WHO-FICs, including the classification, nomenclature, definitions, descriptions, terminology and coding systems, to standardize rehabilitation evaluation and statistics. The management and governance system of rehabilitation should be implemented using WHO-FICs. Rehabilitation services are based on the bio-psycho-social model and implemented the principles of people-centered and functioning-oriented. The systematic implementation of WHO-FICs in rehabilitation abide by the model of "Evaluation (ICHI)－Evaluation, Description, Classification and Coding of Functioning (ICF)－Disease Classification, Diagnosis and Coding (ICD)－Rehabilitation Intervention (ICHI)", and with the standardized process of "Evaluation (Functioning and unmet needs)－Diagnose (Disease and Functioning)－Planning of Rehabilitation－Intervention－Evaluation of Outcome". The mic-modules of implementation of WHO-FICs in rehabilitation had been constructed. There were 28 categories of diseases, 7 categories of functioning and 6 categories of rehabilitation interventions in rehabilitation proposed by International Society of Physical and Rehabilitation Medicine. According to ICD-11 and ICF, it proposed to use WHO Disability Assessment Schedule 2.0 (WHODAS 2.0), Brief Model Disability Survey (MDS-B) and VB40 Generic Functioning Domains (VB40), and the ICF core-sets in evaluation of functioning and rehabilitation outcome. The implementation of WHO-FICs in management of medical records and reporting realized the standardized management of medical record, encoding of diseases, functioning and intervention, reporting of performance, and provided tools for billing, reimbursement and payment management of rehabilitation. It proposed to develop WHO-FICs based clinical data sets and big data to implement functioning-related Diagnosis Related Groups and case-mix statistics. Conclusion:With the systematic implementation of WHO-FICs in rehabilitation, the policy and theoretical framework at macro level had been developed. The mechanism of management and governance at meso level had been explored. The application modules and approaches at micro level had been established. A scientific and effective overall solution had been proposed to enhance the scientific, standardized, refined and informatization level, strengthen the level and governance capacity, and improve the quality, safety and the coverage of rehabilitation services.