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.

Effects of public health interventions and zero COVID policy on paediatric diseases: A Southern China study.

Background: With the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in schools and communities, clinical evidence is needed to determine the impact of the pandemic and public health interventions under the zero coronavirus disease policy on the occurrence of common infectious diseases and non-infectious diseases among children. Methods: The current study was designed to analyse the occurrence of common infectious diseases before and after the pandemic outbreak in southern China. Data was obtained for 1 801 728 patients admitted into children's hospitals in Guangzhou between January 2017 and July 2022. Regression analysis was performed for data analysis. Results: The annual occurrence of common paediatric infectious diseases remarkably decreased after the pandemic compared to the baseline before the pandemic and the monthly occurrence. Cases per month of common paediatric infectious diseases were significantly lower in five periods during the local outbreak when enhanced public health measures were in place. Cases of acute non-infectious diseases such as bone fractures were not reduced. Non-pharmaceutical interventions decreased annual and monthly cases of paediatric respiratory and intestinal infections during the coronavirus disease 2019 (COVID-19) pandemic, especially when enhanced public health interventions were in place. Conclusions: Our findings provide clinical evidence that public health interventions under the dynamic zero COVID policy in the past three years had significant impacts on the occurrence of common respiratory and intestinal infectious diseases among children and adolescents but little impact on reducing non-infectious diseases such as leukaemia and bone fracture.

Safety and efficacy of eltrombopag in the treatment of children with immune thrombocytopenia: a Meta analysis. / è‰¾æ›²æ³Šå¸•æ²»ç–—å„¿ç«¥å ç–«æ€§è¡€å°æ¿å‡å°‘ç—‡çš„Meta分析.

OBJECTIVES: To systematically assess the efficacy and safety of eltrombopag in the treatment of children with immune thrombocytopenia (ITP). METHODS: PubMed, Embase, Cochrane Library, Weipu Data, CNKI, and Wanfang Data were searched for studies on eltrombopag used for the treatment of children with ITP. RevMan 5.3 and R version 3.6 were used to perform a Meta analysis of included studies. RESULTS: A total of 11 studies were included, with 2 randomized controlled trials and 9 cohort studies. The Meta analysis of the 9 cohort studies showed that eltrombopag had a response rate of about 70% (95%CI: 65%-76%) in the treatment of children with ITP, with no serious adverse events. The Meta analysis of the randomized controlled trials showed that the eltrombopag group had a higher response rate than the placebo group (RR=2.64, 95%CI: 1.58-4.44, P<0.05), while there was no significant difference in the incidence rates of adverse events and serious adverse events between the two groups (P>0.05). CONCLUSIONS: Eltrombopag has good efficacy and safety as a second-line treatment regimen for children with ITP.

Therapeutic evidence of umbilical cord-derived mesenchymal stem cell transplantation for cerebral palsy: a randomized, controlled trial.

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 18F-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 18F-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."

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.

The BCL2L11 deletion polymorphism is not associated with imatinib resistance in chronic myeloid leukemia patients: meta-analysis.

A common deletion polymorphism of the gene Bcl-2 like protein 11 (BCL2L11, BIM) has been reported to cause tyrosine kinase inhibitors (TKIs) resistance in several malignant tumors. However, the conclusions were not consistent in chronic myeloid leukemia (CML) individuals. In order to obtain a reliable conclusion, we systematically searched PubMed, Embase, Web of Science, Chinese Biomedical Database, and China National Knowledge Infrastructure and performed the meta-analysis. Six published articles contain 760 East Asian patients were identified from these electronic databases. The methodological quality of one included trial was high, and the others were moderate. Meta-analysis showed that the rate of TKI resistance between the BIM deletion and wild-type group were no statistical significance (OR = 1.24, 95% CI 0.79-1.95). In conclusion, BIM deletion may not a predictor of TKI resistance in CML individuals in East Asia.

Familial tumoral calcinosis in two Chinese patients: a case series.

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.

[Correlation between the ratio of serum vascular endothelial growth factor/endostatin and childhood acute leukemia].

OBJECTIVE: To investigate the correlation between the ratio of serum vascular endothelial growth factor (VEGF)/endostatin (ES) and childhood acute leukemia(AL). METHODS: Serum levels of VEGF and ES were measured using ELISA in 35 children with acute AL before and after chemotherapy. The ratio of VEGF/ES was calculated. Thirty healthy children served as the control group. RESULTS: The serum levels of VEGF (196 ± 66 pg/mL vs 29 ± 10 pg/mL) and ES (35 ± 7 ng/mL vs 19 ± 4 ng/mL) in the AL group before chemotherapy were significantly higher than those in the control group (P<0.01). The ratio of VEGF/ES in the AL group before chemotherapy was significantly higher than that in the control group (6.7 ± 3.0 vs 1.6 ± 0.7; P<0.01). In 20 children with AL who achieved complete remission, the serum levels of VEGF and ES and the VEGF/ES ratio were reduced after chemotherapy (83 ± 35 pg/mL, 27 ± 5 ng/mL, 3.1 ± 1.3, respectively; P<0.01), although the serum levels of VEGF and ES were still higher than those in the control group (P<0.01). The VEGF/ES ratio in CR patients was not significantly different from that in the control group. The serum levels of VEGF (r=0.301, P=0.045) and the VEGF/ES ratio (r=0.411, P=0.015) were positively correlated with the count of blast cells in juvenile bone marrow in 35 children with AL before chemotherapy. CONCLUSIONS: Serum VEGF and ES levels are associated with the development of childhood AL. The VEGF/ES ratio can be used to evaluate the disease progression in children with AL.

Scrotal calcinosis: A case report.

Scrotal 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.