Familial tumoral calcinosis in two Chinese patients: a case series

Abstract Introduction Tumoral calcinosis is a rare and benign condition characterized by massive subcutaneous soft tissue deposits of calcium phosphate predominantly around large joints. Case presentation Familial tumoral calcinosis was present in two members of a Han Chinese family, namely, the son and daughter. The 14-year-old son had the first operation on his right sole of the foot at the age of six, and then experienced subsequent surgeries at a lesion in his right sole of the foot and left hip, respectively. The 16-year-old daughter underwent her first operation at the age of six in her left gluteal region, and subsequent surgeries were performed due to recurrence at the same lesion. Pathologic diagnoses of surgical specimens in both of the patients were reported as tumoral calcinosis. The laboratory results showed hyperphosphatemia with normal levels of serum calcium and alkaline phosphatase. Only surgical treatment was performed in both patients with satisfactory prognosis. Conclusion This is the first report of Chinese familial tumoral calcinosis. The etiopathogenisis and treatment are discussed.</p

Scrotal calcinosis: A case report

AbstractScrotal calcinosis (SC) was a rare and benign condition characterized by multiple calcific substances deposits occurring in scrotum and formed nodules and lumps within scrotal skin. A case of a 49-year-old male patient with a 7-year history of scrotal calcinosis was reported. Histopathological findings had not showed evidences of epithelial structures. In our case, no evidence of cystic structure was found around calcified materials. It was indicated that SC might be idiopathic

Human umbilical cord mesenchymal stem cell therapy for renal dysfunction in Alport syndrome: protocol for an open-label, single-arm trial in China

Introduction Alport syndrome (AS) is one of the most common fatal hereditary renal diseases in human, with a high risk of progressing to end-stage renal disease without effective treatments. Mesenchymal stem cells (MSCs) have recently emerged as a promising therapeutic strategy for chronic kidney disease. However, the safety and therapeutic potential of MSC transfusion for patients with AS are still need to be confirmed. Therefore, we have designed a clinical trial to evaluate the hypothesis that intravenous infusion of human umbilical cord-derived MSC (hUC-MSC) is safe, feasible, and well-tolerated in children with AS.Methods and analysis We report the protocol of the first prospective, open-label, single-arm clinical trial to evaluate the safety and preliminary efficacy of hUC-MSC transfusion in children with early-stage AS. Paediatric patients diagnosed with AS who have persistent albuminuria will be candidates for screening. Twelve eligible patients are planned to recruit and will receive hUC-MSC infusions under close safety monitoring, and complete the efficacy assessments at scheduled follow-up visits. The primary endpoints include the occurrence of adverse events to assess safety and the albuminuria level for efficacy evaluation. Secondary endpoint assessments are based on haematuria and glomerular filtration measurements. Each patient’s efficacy endpoints will be evaluated against their baseline levels. Additionally, the underlying mechanism of hUC-MSC therapy will be explored through transcriptomic and proteomic analysis of blood and urine samples.Ethics and dissemination The protocol (V.1.0, date 17 January 2015) was approved by the institutional review board of the Affiliated Taihe Hospital of Hubei University of Medicine (ethical approval 03 March 2015). Written informed consent will be obtained from the patient and/or guardians before study specific process. In addition to publication in a peer-reviewed scientific journal, a lay summary of study will be available for participants and the public on the Chinese Organization for Rare Disorders website (http://www.cord.org.cn/).Trial registration number ISRCTN62094626

Therapy for Cerebral Palsy by Human Umbilical Cord Blood Mesenchymal Stem Cells Transplantation Combined With Basic Rehabilitation Treatment

Background . Cerebral palsy (CP) is the most common cause leading to childhood disability. Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) transplantation is a promising alternative considering the safety and efficacy in current reports. This report represents a case of hUCB-MSCs transplantation combined with basic rehabilitation treatment beginning as early as age 6 months with follow-up as long as 5 years. Methods . A 6-year-old female patient was diagnosed with CP at age 6 months. The patient accepted 4 infusions of intravenous hUCB-MSCs in each course and received 4 courses of transplantation totally. A series of assessments were performed before the first transplantation, including laboratory tests, CDCC Infant Mental Development Scale, and Gross Motor Function Measure-88 (GMFM-88). Then annual assessments using the GMFM-88, Ashworth spasm assessment, and comprehensive function assessment scale were made in addition to the annual laboratory tests. In addition, electroencephalography and brain magnetic resonance imaging were conducted before transplantation and in the follow-up phase. Rehabilitation and safety follow-up have been ongoing for 5 years up to date. Results . There was no complaint about adverse effects during hospitalization or postoperative follow-up. Motor function recovered to normal level according to the evaluation of scales. Language function improved significantly. Linguistic rehabilitation therapy was enhanced for further improvement. Conclusions . The clinical application of hUC-MSCs combined with basic rehabilitation treatment was effective and safe for improving motor and comprehensive function in a patient with CP

Clinical and epidemiological characteristics of pediatric SARS-CoV-2 infections in China: A multicenter case series.

BackgroundAs 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 findingsThis 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 high-sensitivity 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 available data; 78%). In addition, significant increases in the levels of lactate dehydrogenase and α-hydroxybutyrate dehydrogenase were detected in 28 patients (among 34 patients with available data; 82%) and 25 patients (among 34 patients with available data; 74%), respectively. Patchy lesions in lobules were detected by chest computed tomographic scans in 28 patients (82%). Ground-glass opacities, which were a typical feature in adults, were rare in pediatric patients (3%). Rapid radiologic progression and a late-onset pattern of lesions in the lobules were also noticed. Lesions in lobules still existed in 24 (among 32 patients with lesions; 75%) patients that were discharged, although the main symptoms disappeared a few days after treatment. All patients were discharged, and the median duration of hospitalization was 10.00 (8.00-14.25) days. The current study was limited by the small sample size and a lack of dynamic detection of inflammatory markers.ConclusionsOur data systemically presented the clinical and epidemiological features, as well as the outcomes, of pediatric patients with COVID-19. Stratified analysis was performed between mild and moderate cases. The findings offer new insight into early identification and intervention in pediatric patients with COVID-19

A Randomized, Placebo-Controlled Trial of Human Umbilical Cord Blood Mesenchymal Stem Cell Infusion for Children With Cerebral Palsy

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. </jats:p

Clinical Characteristics of 34 Children with Coronavirus Disease-2019 in the West of China: a Multiple-center Case Series

AbstractBackgroundUp to 9 March, 2020, 109577 patients were diagnosed with coronavirus disease-2019 (COVID-19) globally. The clinical and epidemiological characteristics of adult patients have been revealed recently. However, the information of paediatric patients remains unclear. We describe the clinical and epidemiological characteristics of paediatric patients to provide valuable insight into early diagnosis of COVID-19 in children, as well as epidemic control policy making.Methods and FindingsThis retrospective, observational study was a case series performed at 4 hospitals in the west of China. Thirty-four paediatric patients with COVID-19 were included from January 1 to February 25, 2020. And the final follow-up visit was completed by February 28, 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 on 34 paediatrics patients with COVID-19 aged from 1 to 144 months (median 33.00, IQR 10.00 - 94.25), among whom 14 males (41.18%) were included. 47.60% of patients were noticed without any exposure history. The median incubation period was 10.50 (7.75 - 25.25) days. Infections of other respiratory pathogens were reported in 16 patients (47.06%). The most common initial symptoms were fever (76.47%), cough (58.82%), and expectoration (20.59%). Vomiting (11.76%) and diarrhea (11.76%) were also reported in a considerable portion of cases. A remarkable increase was detected in serum amyloid A for 17 patients (85.00%) and high-sensitivity C-reactive protein for 17 patients (58.62%), while a decrease of prealbumin was noticed in 25 patients (78.13%). In addition, the levels of lactate dehydrogenase was increased significantly in 28 patients (82.35%), as well as α-hydroxybutyrate dehydrogenase in 25 patients (73.53%). Patchy lesions in lobules were detected by chest computed tomographic scans in 28 patients (82.36%). The typical feature of ground-glass opacity for adults was rare in paediatric patients (2.94%). A late-onset pattern of lesions in lobules were also noticed. Stratified analysis of the clinical features were not performed due to relatively limited samples.ConclusionsOur data presented the clinical and epidemiological features of paediatric patients systemically. The findings offer new insight into the early identification and intervention of paediatric patients with COVID-19.Author summaryWhy was this study done?The 2019-novel coronavirus (2019-nCoV) infection has spread worldwide rapidly.Early identification and intervention are necessary for effective epidemic control in both adults and children, however the clinical and epidemiological characteristics of paediatric patients remains unclear.What did the researchers do and find?We collected and analyzed clinical data of 34 paediatric patients with coronavirus disease-2019 (COVID-19) in 4 hospitals of China from January 1 to February 25, 2020.We described the clinical and epidemiological features of the patients, and focused on the differences in initial symptoms and radiological findings between paediatric patients and adult patients.Distinguished from adult patients, higher incidences of fever, vomiting, and diarrhea were noticed on admission in paediatric cases.Patchy shadows of high density were common in lobules lesions, while the typical features of ground-glass opacity in adults were rare in paediatric cases.A late-onset pattern of lobules lesions was revealed on the basis of chest computed tomographic scans.What do these findings mean?The specific clinical features in paediatric patients should be paid more attention to, when the physicians are dealing with suspected cases.The epidemiological model in children was characterized with dominant family cluster transmission and extended incubation period, which should be taken into consideration in policy making for epidemic control.</jats:sec

Novel miRNA markers and their mechanism of esophageal squamous cell carcinoma (ESCC) based on TCGA

Abstract MicroRNAs(miRNAs) are promising biomarkers for early esophageal squamous cell carcinoma (ESCC) detection and prognostic prediction. This study aimed to explore the potential biomarkers and molecular pathogenesis in the early diagnosis of ESCC. Firstly, 48 differentially expressed miRNAs (DEMs) and 1319 differentially expressed genes (DEGs) were identified between 94 ESCC tissues and 13 normal esophageal tissues in TCGA. From miRNA–mRNA regulatory network, there are 6558 target genes of the 48 DEMs, where 400 target genes are also among 1319 DEGs. Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment indicate that the 400 DEGs significantly enriched in cell cycle, proteoglycans in cancer, p53 signaling pathway, protein digestion and absorption, transcriptional dysregulation in cancer, and oocyte meiosis. And there are 66 DEGs among these six biological pathways, which we called GO-DEGs. From miRNA–mRNA regulatory network, 32 DEMs regulated the 66 GO-DEGs, where 22 DEMs were verified by different types of experiments in ESCC tissues, cells, or serum from the literature. For the other novel 10 DEMs, single-factor Cox regression analysis show that only hsa-miR-34b-3p showed no significant correlation with the overall survival of ESCC patients. Finally, we obtained the novel 9 ESCC-related DEMs, where three are down-regulated, and six are up-regulated. We analyzed the expression trends of target genes for five miRNAs and identified three significantly different miRNAs (hsa-miR-205-3p, hsa-miR-452-3p, and hsa-miR-6499-3p) confirmed by qPCR. Moreover, the stage-specific miRNAs were also suggested. These three qPCR validated miRNAs are also specific to the early stages of ESCC: hsa-miR-452-3p is specific to Stage I, II and III; hsa-miR-205-3p is specific in Stage II and III; and hsa-miR-6499-3p is Stage II specific. They might be the potential biomarkers for ESCC stage diagnosis. This study identified three novel miRNA markers potentially related to the diagnosis of ESCC and participated in the occurrence and development of ESCC through cell cycle, proteoglycans in cancer, p53 signaling pathway, protein digestion and absorption, transcriptional dysregulation in cancer, and signaling pathway for oocyte meiosis