Background As of April 18, 2020, over 2,000,000 patients had been diagnosed with coronavirus disease-2019 (COVID-19) globally, and more than 140,000 deaths had been reported. The clinical and epidemiological characteristics of adult patients have been documented recently. However, information on pediatric patients is limited. We describe the clinical and epidemiological characteristics of pediatric patients to provide valuable insight into the early diagnosis and assessment of COVID-19 in children. Methods and findings This retrospective, observational study involves a case series performed at 4 hospitals in West China. Thirty-four pediatric patients with COVID-19 were included from January 27 to February 23, 2020. The final follow-up visit was completed by March 16, 2020. Clinical and epidemiological characteristics were analyzed on the basis of demographic data, medical history, laboratory tests, radiological findings, and treatment information. Data analysis was performed for 34 pediatrics patients with COVID-19 aged from 1 to 144 months (median 33.00, interquartile range 10.00-94.25), among whom 14 males (41%) were included. All the patients in the current study presented mild (18%) or moderate (82%) forms of COVID-19. A total of 48% of patients were noted to be without a history of exposure to an identified source. Mixed infections of other respiratory pathogens were reported in 16 patients (47%). Comorbidities were reported in 6 patients (18%). The most common initial symptoms were fever (76%) and cough (62%). Expectoration (21%), vomiting (12%), and diarrhea (12%) were also reported in a considerable portion of cases. A substantial increase was detected in serum amyloid A for 17 patients (among 20 patients with available data; 85%) and in highsensitivity C-reactive protein for 17 patients (among 29 patients with available data; 59%), whereas a decrease in prealbumin was noticed in 25 patients (among 32 patients with a1111111111 a1111111111 a1111111111 a1111111111 a1111111111
Cerebral palsy (CP) is a common disability which results in permanent chronic motor disability appearing in early childhood. Recently human umbilical cord blood mesenchymal stem cell (hUCB-MSC) infusion has emerged as a promising therapeutic strategy for CP, and the treatment efficacy remains to be confirmed by clinical trials. All 54 patients received basic rehabilitation as a background treatment. The infusion group comprising 27 patients received 4 infusions of hUCB-MSCs (intravenous infusions at a fixed dose of 5 × 107) and basic rehabilitation treatment, whereas 27 patients in the control group received 0.9% normal saline and basic rehabilitation treatment. Several indices were tested from baseline up to 24 months posttreatment regarding efficacy and safety evaluations, including the gross motor function measurement 88 (GMFM-88) scores, the comprehensive function assessment (CFA), lab tests, electroencephalogram (EEG), routine magnetic resonance imaging (MRI), and adverse events. The changes in the total proportion of GMFM-88 and total scores of CFA in the hUCB-MSC infusion group were significantly higher than that in control group at 3, 6, 12, 24 months posttreatment. Less diffuse slow waves were noticed after hUCB-MSC infusion in patients with slowing of EEG background rhythms at baseline. Based on the routine MRI exams, improvements in cerebral structures were rare after treatment. Serious adverse events were not observed during the whole study period. The results of the study indicated that hUCB-MSC infusion with basic rehabilitation was safe and effective in improving gross motor and comprehensive functions in children with CP.
Background: Cerebral palsy (CP) is a syndrome of childhood movement and posture disorders. Clinical evidence is still limited and sometimes inconclusive about the benefits of human umbilical cord mesenchymal stem cells (hUC-MSCs) for CP. We conducted a randomized trial to evaluate the safety and efficacy of hUC-MSC transplantation concomitant with rehabilitation in patients with CP. Methods: Eligible patients were allocated into the hUC-MSC group and control group. In addition to rehabilitation, the patients in the hUC-MSC group received four transfusions of hUC-MSCs intravenously, while the control group received a placebo. Adverse events (AEs) were collected for safety evaluation in the 12-month follow-up phase. Primary endpoints were assessed as activities of daily living (ADL), comprehensive function assessment (CFA), and gross motor function measure (GMFM) scales. In addition, cerebral metabolic activity was detected by 18 F-FDG-PET/ CT to explore the possible mechanism of the therapeutic effects. Primary endpoint data were analyzed by ANOVA using SPSS version 20.0. Results: Forty patients were enrolled, and 1 patient withdrew informed consent. Therefore, 39 patients received treatments and completed the scheduled assessments. No significant difference was shown between the 2 groups in AE incidence. Additionally, significant improvements in ADL, CFA, and GMFM were observed in the hUC-MSC group compared with the control group. In addition, the standard uptake value of 18 F-FDG was markedly increased in 3 out of 5 patients from the hUC-MSC group at 12 months after transplantation. Conclusions: Our clinical data showed that hUC-MSC transplantation was safe and effective at improving the gross motor and comprehensive function of children with CP when combined with rehabilitation. Recovery of cerebral metabolic activity might play an essential role in the improvements in brain function in patients with CP. The therapeutic window, transfusion route, and dosage in our study were considerable for reference in clinical application. Trial registration: Chictr.org.cn, ChiCTR1800016554. Registered 08 June 2018-retrospectively registered. The public title was "Randomized trial of umbilical cord-derived mesenchymal stem cells for cerebral palsy."
Biodegradable polymer/bioceramic composites scaffold can overcome the limitation of conventional ceramic bone substitutes such as brittleness and difficulty in shaping. To better mimic the mineral component and the microstructure of natural bone, novel nano-hydroxyapatite (NHA)/polymer composite scaffolds with high porosity and well-controlled pore architectures as well as high exposure of the bioactive ceramics to the scaffold surface is developed for efficient bone tissue engineering. In this article, regular and highly interconnected porous poly(lactide-co-glycolide) (PLGA)/NHA scaffolds are fabricated by thermally induced phase separation technique. The effects of solvent composition, polymer concentration, coarsening temperature, and coarsening time as well as NHA content on the micro-morphology, mechanical properties of the PLGA/NHA scaffolds are investigated. The results show that pore size of the PLGA/NHA scaffolds decrease with the increase of PLGA concentration and NHA content. The introduction of NHA greatly increase the mechanical properties and water absorption ability which greatly increase with the increase of NHA content. Mesenchymal stem cells are seeded and cultured in *Author to whom correspondence should be addressed. E-mail: renjie@mail.tongji.edu.cn three-dimensional (3D) PLGA/NHA scaffolds to fabricate in vitro tissue engineering bone, which is investigated by adhesion rate, cell morphology, cell numbers, and alkaline phosphatase assay. The results display that the PLGA/NHA scaffolds exhibit significantly higher cell growth, alkaline phosphatase activity than PLGA scaffolds, especially the PLGA/NHA scaffolds with 10 wt.% NHA. The results suggest that the newly developed PLGA/NHA composite scaffolds may serve as an excellent 3D substrate for cell attachment and migration in bone tissue engineering.
Aim: We compared the clinical and physiological consequences of the novel mutation R878C in a highly conserved pore residue in domain II (S5-S6) of human, hNa v 1.5, cardiac Na + channels.Methods: Full clinical evaluation of pedigree members through three generations of a Chinese family combined with SCN5A sequencing from genomic DNA was compared with patch and voltage-clamp results from two independent expression systems.Results: The four mutation carriers showed bradycardia, and slowed sinoatrial, atrioventricular and intraventricular conduction. Two also showed sick sinus syndrome; two had ST elevation in leads V1 and V2. Unlike WT-hNa v 1.5, whole-cell patch-clamped HEK293 cells expressing R878C-hNa v 1.5 showed no detectable Na + currents (i Na ), even with substitution of a similarly charged lysine residue. Voltage-clamped Xenopus oocytes injected with either 0.04 or 1.5 lg lL )1 R878C-hNa v 1.5 cRNA similarly showed no i Na , yet WT-hNa v 1.5 cRNA diluted to 0.0004-0.0008 ng lL )1 resulted in expression of detectable i Na . i Na was simply determined by the amount of injected WT-hNa v 1.5: doubling the dose of WT-hNa v 1.5 cRNA doubled i Na . i Na amplitudes and activation and inactivation characteristics were similar irrespective of whether WT-hNa v 1.5 cRNA was given alone or combined with equal doses of R878C-hNa v 1.5 cRNA therefore excluding dominant negative phenotypic effects. Na + channel function in HEK293 cells transfected with R878C-hNa v 1.5 was not restored by exposure to mexiletine (200 lm) and lidocaine (100 lm). Fluorescence confocal microscopy using E3-Nav1.5 antibody demonstrated persistent membrane expression of both WT and R878C-hNa v 1.5. Modelling studies confirmed that such i Na reductions reproduced the SSS phenotype. Conclusion: Clinical consequences of the novel R878C mutation correlate with results of physiological studies.
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