Comprehensive Proteomics Analysis Identifies CD38-Mediated NAD+ Decline Orchestrating Renal Fibrosis in Pediatric Patients With Obstructive Nephropathy.

Obstructive nephropathy is one of the leading causes of kidney injury and renal fibrosis in pediatric patients. Although considerable advances have been made in understanding the pathophysiology of obstructive nephropathy, most of them were based on animal experiments and a comprehensive understanding of obstructive nephropathy in pediatric patients at the molecular level remains limited. Here, we performed a comparative proteomics analysis of obstructed kidneys from pediatric patients with ureteropelvic junction obstruction and healthy kidney tissues. Intriguingly, the proteomics revealed extensive metabolic reprogramming in kidneys from individuals with ureteropelvic junction obstruction. Moreover, we uncovered the dysregulation of NAD+ metabolism and NAD+-related metabolic pathways, including mitochondrial dysfunction, the Krebs cycle, and tryptophan metabolism, which led to decreased NAD+ levels in obstructed kidneys. Importantly, the major NADase CD38 was strongly induced in human and experimental obstructive nephropathy. Genetic deletion or pharmacological inhibition of CD38 as well as NAD+ supplementation significantly recovered NAD+ levels in obstructed kidneys and reduced obstruction-induced renal fibrosis, partially through the mechanisms of blunting the recruitment of immune cells and NF-κB signaling. Thus, our work not only provides an enriched resource for future investigations of obstructive nephropathy but also establishes CD38-mediated NAD+ decline as a potential therapeutic target for obstruction-induced renal fibrosis.

A comprehensive study on machine learning models combining with oversampling for bronchopulmonary dysplasia-associated pulmonary hypertension in very preterm infants.

BACKGROUND: Bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) remains a devastating clinical complication seriously affecting the therapeutic outcome of preterm infants. Hence, early prevention and timely diagnosis prior to pathological change is the key to reducing morbidity and improving prognosis. Our primary objective is to utilize machine learning techniques to build predictive models that could accurately identify BPD infants at risk of developing PH. METHODS: The data utilized in this study were collected from neonatology departments of four tertiary-level hospitals in China. To address the issue of imbalanced data, oversampling algorithms synthetic minority over-sampling technique (SMOTE) was applied to improve the model. RESULTS: Seven hundred sixty one clinical records were collected in our study. Following data pre-processing and feature selection, 5 of the 46 features were used to build models, including duration of invasive respiratory support (day), the severity of BPD, ventilator-associated pneumonia, pulmonary hemorrhage, and early-onset PH. Four machine learning models were applied to predictive learning, and after comprehensive selection a model was ultimately selected. The model achieved 93.8% sensitivity, 85.0% accuracy, and 0.933 AUC. A score of the logistic regression formula greater than 0 was identified as a warning sign of BPD-PH. CONCLUSIONS: We comprehensively compared different machine learning models and ultimately obtained a good prognosis model which was sufficient to support pediatric clinicians to make early diagnosis and formulate a better treatment plan for pediatric patients with BPD-PH.

End-organ damage from neonatal invasive fungal infection: a 14-year retrospective study from a tertiary center in China.

BACKGROUND: Invasive fungal infection (IFI) has become an increasing problem in NICU neonates, and end-organ damage (EOD) from IFI is one of the leading causes of morbidity and mortality in neonates. This study was conducted to summarize clinical data on epidemiology, risk factors, causative pathogens, and clinical outcomes of IFI-associated EOD among neonates in a center in China for the sake of providing references for prevention and treatment of fungal infections in neonates in future. METHODS: The clinical data of IFI neonates who received treatment in a tertiary NICU of China from January 2009 to December 2022 were retrospectively analyzed, including causative pathogens and the incidence of EOD. The neonates were divided into EOD group and non-EOD (NEOD) group. The general characteristics, risk factors and clinical outcomes of the two groups were compared. RESULTS: Included in this study were 223 IFI neonates (137 male and 86 female) with a median gestational age (GA) of 30.71 (29,35) weeks and a median birth weight (BW) of 1470 (1120,2150) g. Of them, 79.4% were preterm infants and 50.2% were born at a GA of ≥ 28, <32 weeks, and 37.7% with BW of 1000-1499 g. Candida albicans (C. albicans) was the most common Candida spp. in these neonates, accounting for 41.3% of all cases, followed by C. parapsilosis (30.5%) and C. glabrata (7.2%). EOD occurred in 40 (17.9%) of the 223 cases. Fungal meningitis was the most common EOD, accounting for 13.5% of the 40 EOD cases. There was no significant difference in the premature birth rate, delivery mode, GA and BW between EOD and NEOD groups, but the proportion of male infants with EOD was higher than that without. There was no significant difference in antenatal corticosteroid use, endotracheal intubation, invasive procedures, use of antibiotics, total parenteral nutrition, blood transfusion, postnatal corticosteroid use, fungal prophylaxis and the incidence of necrotizing enterocolitis between the two groups, but the proportion of C. albicans infection cases in EOD group was higher than that in NEOD group (57.5% vs. 37.7%). Compared with NEOD group, the proportion of cured or improved infants in EOD group was significantly lower (P < 0.05), and the number of infants who died or withdrew from treatment was larger (P < 0.05). CONCLUSIONS: Our retrospective study showed that preterm infants were prone to fungal infection, especially very preterm infants. C. albicans was the most common Candida spp. for IFI, and was a high-risk factor for EOD. EOD can occur in both full-term and premature infants, so the possibility of EOD should be considered in all infants with IFI.

Pathogens in PICU before and during the SARS-CoV-2 pandemic in China: a multicenter retrospective study.

BACKGROUND: Nonpharmacological interventions for COVID-19 could reduce the incidence of children hospitalized in pediatric intensive care units (PICU) and the incidence of children with bacterial infections. This study aimed to evaluate changes in the bacterial profile of children in PICU before and during the COVID-19 pandemics. METHODS: This is a retrospective study, involving clinical data of children with positive bacterial cultures admitted to the PICU respectively in 2019 and 2021. RESULTS: In total 652 children were included in this study. The total number of hospitalized patients and the incidence of bacteria-positive children in 2021 were lower than those in 2019. There were no significant differences in the ratio of Gram-positive bacterial infection, Gram-negative bacteria infection or fungi infection between the two years. The rate of Streptococcus pneumoniae in 2021 was higher than that in 2019(p = 0.127). The incidence of Haemophilus influenzae in hospitalized patients decreased with a downward trend(p = 0.002). The distribution of previous underlying diseases in children admitted to PICU with different outcomes of bacterial infection between the two years were homogeneous (p > 0.05). CONCLUSION: After the implementation of COVID-19 isolation, prevention and control measures, the number of hospitalizations and bacterial infections in PICU decreased, which may be due to changes in population's behavior patterns. Meanwhile, the incidence of Haemophilus influenzae in hospitalized patients decreased with a downward trend.

Busulfan for Allogeneic Hematopoietic Stem Cell Transplantation in Children with Severe Aplastic Anemia: A Retrospective Study.

INTRODUCTION: This retrospective study aimed to compare a range of conditioning regimens in children with severe aplastic anemia (SAA) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the Seventh Medical Center of PLA General Hospital between January 2008 and June 2017. METHODS: Patients were categorized into the Bu (Bu + Flu + Cy + ATG-F regimen) and control (Flu + Cy + ATG-F) groups, with a median follow-up time after HSCT of 3.5 (range, 3.1-6.2) and 3.7 (3.2-5.9) years in the Bu and control groups, respectively. RESULTS: No differences were observed between the two groups regarding the median time of peripheral blood neutrophil and platelet engraftment (p = 0.538 and p = 0.491); the 28-day engraftment rates of neutrophils were similar (p = 0.199), although higher for platelets with Bu (p = 0.044). Additionally, graft failure was 0% and 20.0% in the Bu and control groups, respectively (p = 0.004). In both groups, the incidence of grades III-IV (or grades II-IV) acute graft-versus-host disease (GVHD) and chronic GVHD was not significantly different (p > 0.05). Moreover, the 3-year overall survival and failure-free survival did not show significant differences (p = 0.670 and p = 0.908). DISCUSSION: In children with SAA undergoing allo-HSCT, conditioning regimen with Bu + Flu + Cy + ATG-F is capable of enhancing the myeloablation effect, promoting donor hematopoietic stem cell engraftment, and reducing the graft failure rate. Furthermore, it does not increase the incidence of complications, including GVHD.

Experience of treating congenital complete atrioventricular block with epicardial pacemaker in infants and young children: a retrospective study.

BACKGROUND: This article summarizes the treatment experience for congenital complete atrioventricular block (CCAVB) in newborns and infants, and discusses the necessity and feasibility of treating CCAVB with permanent pacemaker implantation in this population. METHODS: In this study, the clinical data and follow-up results of nine children admitted at our center with CCAVB from January 2005 to March 2023 were retrospectively analyzed. Among them, two children received early implantation of permanent pacemakers (within 1 year of age), two children received non-early implantation (1 year or older), and the remaining five children received no pacemaker implantation. CCAVB diagnosis was confirmed by clinical symptoms and clinical examinations, including electrocardiography and echocardiography before surgery. After surgery, the pacing and sensing functions of the pacemaker were observed using electrocardiography, echocardiography, and pacing threshold monitoring. A comprehensive assessment of the treatment efficacy was conducted, encompassing improvements in clinical symptoms, growth and development, as well as the absence of any additional potential complications. The children who did not receive pacemaker implantation were followed up. RESULTS: Among the four children who successfully received pacemaker implantation, one child who received non-early implantation died. For the remaining three children, the threshold level, amplitude, impedance, and minute ventilation sensor function of the pacemaker were good during the follow-up period, with a heart rate at the pacing rate. The growth and development of the aforementioned patients who received pacemaker implantation demonstrated adherence to the percentile curve, and their motor and cognitive development remained unaffected. However, among the children who did not undergo pacemaker implantation, two experienced death, while three were lost to follow-up, thereby limiting the evaluation of their long-term outcomes. CONCLUSIONS: Early implantation of an epicardial pacemaker at an early stage in newborns and infants diagnosed with CCAVB can significantly improve clinical symptoms without affecting their growth and development. These data are in line with current literature and suggest that early implantation of an epicardial pacemaker in newborns and infants diagnosed with CCAVB but further studies are needed.

Comparison of post-treatment recurrence between ranibizumab injection and laser photocoagulation for type 1 retinopathy of prematurity.

OBJECTIVE: To compare post-treatment recurrence between ranibizumab injection and laser photocoagulation (LP) for type 1 retinopathy of prematurity (ROP), and explore the associated risk factors. METHODS: The clinical data of ROP infants treated with LP or ranibizumab in a NICU of China from October 2007 to November 2021 were retrospectively analyzed and compared, such as general condition, degree of ROP, therapeutic effectiveness and post-treatment recurrence. The dependent variable was recurrence after ROP treatment. Univariate and regression analysis of risk factors was performed. RESULTS: Of the 298 ROP infants (556 eyes), 58% of the eyes were treated with LP and the other 42% with ranibizumab. There was no significant difference in gestational age at birth, birth weight, sex, delivery mode, prenatal corticosteroids, ROP diagnosed before admission or after admission, and the duration of oxygen therapy between the two groups. However, the ratio of type 1 ROP and aggressive retinopathy of prematurity (A-ROP) in ranibizumab group was higher than that in LP group. The number of treatments, recurrence rate and recurrence interval in ranibizumab group were higher than those in LP group. However, there was no difference in the recurrence rate between the two groups after stratified analysis by the lesion area and the presence or absence of A-ROP. There was no significant difference in the final lesion regression between the two groups. Regression analysis showed that plus disease and ROP located in zone I were independent risk factors for post-treatment recurrence. CONCLUSION: There is no significant difference in the recurrence rate of ROP between ranibizumab injection and LP, and recurrence is mainly related to the severity of ROP. In half of our patients treated with A-ROP recurrences occur.

Positive association between arterial blood lactate level before extra-corporeal membrane oxygenation and 30-day mortality in pediatric patients with severe cardiopulmonary failure.

INTRODUCTION: This study aimed to investigate the relationship between blood lactate level and mortality in pediatric patients receiving extracorporeal membrane oxygenation (ECMO) for severe cardiopulmonary failure. METHODS: A retrospective observational study was conducted on pediatric patients who received ECMO from January 2013 to December 2021 at the Seventh Medical Center of PLA General Hospital. Patient demographic characteristics, arterial blood lactate level prior to ECMO (pre-ECMO), ECMO settings, ECMO duration, and 30-days mortality were retrieved from patients' medical records. The relationships between pre-ECMO blood lactate level and mortality were interpreted using the logistic regression analysis and Kaplan-Meier survival analysis. RESULTS: A total of 160 pediatric patients who had either refractory respiratory failure (n = 89) or circulatory failure (n = 71) and received ECMO were included in this study. In both the respiratory failure and circulatory failure groups, the non-survivors showed a higher mean pre-ECMO arterial blood lactate level than the survivors. In the respiratory failure group, a pre-ECMO lactate concentration at ≥11.6 mmol/L had a sensitivity of 51% and a specificity of 82% for predicting mortality. In the circulatory failure group, a pre-ECMO lactate concentration at ≥7.2 mmol/L had a sensitivity of 90% and a specificity of 57% for predicting mortality. The Kaplan-Meier survival curves showed that respiratory failure patients with a pre-ECMO lactate level over 11.6 mmol/L or circulatory failure patients with a pre-ECMO lactate level over 7.2 mmol/L had a higher 30-days mortality rate than those with a lower lactate level. CONCLUSIONS: High pre-ECMO arterial blood lactate level serves as an independent risk factor for mortality in pediatric patients who receive ECMO for severe cardiopulmonary failure.

Predicting risk of severe neonatal outcomes in preterm infants born from mother with prelabor rupture of membranes.

BACKGROUND: Perinatal complications are common burdens for neonates born from mother with pPROM. Physicians and parents sometimes need to make critical decisions about neonatal care with short- and long-term implications on infant's health and families and it is important to predict severe neonatal outcomes with high accuracy. METHODS: The study was based on our prospective study on 1001 preterm infants born from mother with pPROM from August 1, 2017, to March 31, 2018 in three hospitals in China. Multivariable logistic regression analysis was applied to build a predicting model incorporating obstetric and neonatal characteristics available within the first day of NICU admission. We used enhanced bootstrap resampling for internal validation. RESULTS: One thousand one-hundred pregnancies with PROM at preterm with a single fetus were included in our study. SNO was diagnosed in 180 (17.98%) neonates. On multivariate analysis of the primary cohort, independent factors for SNO were respiratory support on the first day,, surfactant on day 1, and birth weight, which were selected into the nomogram. The model displayed good discrimination with a C-index of 0.838 (95%CI, 0.802-0.874) and good calibration performance. High C-index value of 0.835 could still be reached in the internal validation and the calibration curve showed good agreement. Decision curve analysis showed if the threshold is > 15%, using our model would achieve higher net benefit than model with birthweight as the only one predictor. CONCLUSION: Variables available on the first day in NICU including respiratory support on the first day, the use of surfactant on the first day and birthweight could be used to predict the risk of SNO in infants born from mother with pPROM with good discrimination and calibration performance.

Association of variants m.T16172C and m.T16519C in whole mtDNA sequences with high altitude pulmonary edema in Han Chinese lowlanders.

BACKGROUND: High altitude pulmonary edema (HAPE) is a hypoxia-induced non-cardiogenic pulmonary edema that typically occurred in un-acclimatized lowlanders, which inevitably leads to life-threatening consequences. Apart from multiple factors involved, the genetic factors also play an important role in the pathogenesis of HAPE. So far, researchers have put more energy into the nuclear genome and HAPE, and ignored the relationship between the mitochondrion DNA (mtDNA) variants and HAPE susceptibility. METHODS: We recruited a total of 366 individuals including 181 HAPE patients and 185 non-HAPE populations through two times. The first time, 49 HAPE patients and 58 non-HAPE individuals were performed through whole mtDNA sequences to search the mutations and haplogroups. The second time, 132 HAPE patients and 127 non-HAPE subjects were collected to apply verifying these mutations and haplogroups of mtDNA with the routine PCR method. RESULTS: We analyzed and summarized the clinical characteristics and sequence data for the 49 HAPE patients and 58 non-HAPE individuals. We found that a series of routine blood indexes including systolic arterial blood pressure (SBP), heart rate (HR), white blood cell (WBC), and C-reactive protein (CRP) in the HAPE group presented higher and displayed significant differences compared with those in the non-HAPE group. Although the average numbers of variants in different region and group samples were not statistically significant (P > 0.05), the mutation densities of different regions in the internal group showed significant differences. Then we found two mutations (T16172C and T16519C) associated with the HAPE susceptibility, the T16172C mutation increased the risk of HAPE, and the T16519C mutation decreased the HAPE rating. Furthermore, the two mutations were demonstrated with 132 HAPE patients and 127 non-HAPE individuals. Unfortunately, all the haplogroups were not associated with the HAPE haplogroups. CONCLUSIONS: We provided evidence of differences in mtDNA polymorphism frequencies between HAPE and non-HAPE Han Chinese. Genotypes of mtDNA 16172C and 16519C were correlated with HAPE susceptibility, indicating the role of the mitochondrial genome in the pathogenesis of HAPE.

Ventricular septal intramyocardial dissection after cardiac tumor excision.

We reported a rare case: an infant underwent cardiac tumor resection, and postoperative transthoracic echocardiography revealed a cystic dissection located in the interventricular septum.

Pectoralis major muscle turnover flap reconstruction for treatment of deep sternal wound infection in infants and children.

OBJECTIVE: The aim of the study is to assess the therapeutic effect and applicability of pectoralis major muscle turnover flap (PMMTF) reconstruction for treatment of deep sternal wound infection (DSWI) after cardiac surgery in infants and children. METHODS: From March 2013 to October 2021, 23 patients with DSWI after cardiac surgery underwent PMMTF reconstruction. The data and outcomes of the patients were retrospectively analyzed. RESULTS: Twenty patients were treated with unilateral PMMTF reconstruction, and three patients were treated by bilateral PMMTF. All of the sternal wounds healed successfully. All patients survived and were discharged without evidence of infection. In a follow-up period, ranging from 15 to 83 months (mean 32.6 months), all patients demonstrated normal development with no limitations to limb movements. There were no signs of chronic sternal infection in all of them. CONCLUSION: PMMTF reconstruction is a simple, feasible, and effective treatment of DSWI after cardiac surgery in infants and children, with minimal developmental problems.

Window anastomosis technique for repair of supracardiac total anomalous pulmonary venous connection in infants.

Outcomes of operations for total anomalous pulmonary venous connection (TAPVC) have improved. However, postoperative pulmonary venous obstruction remains the most significant complication with high morbidity and mortality. We introduce a window anastomosis technique for repair of supracardiac TAPVC in infants. The mainstay of the surgical technique is to resect the anterior wall of the pulmonary vein confluence and part of the posterior wall of the left atrium to form a large and undistorted "window to window" anastomosis.

Circular RNA circFADS2 is overexpressed in sepsis and suppresses LPS-induced lung cell apoptosis by inhibiting the maturation of miR-15a-5p.

BACKGROUND: Circular RNA circFADS2 plays protective roles in LPS-induced inflammation, which promotes sepsis, suggesting its involvement in sepsis. METHODS: Expression of circFADS2, mature miR-15a-5p, and miR-15a-5p precursor in plasma samples from sepsis patients and healthy controls was determined by RT-qPCR. The circFADS2 expression vector was transfected in lung cells, followed by the measurement of the expression levels of mature miR-15a-5p and miR-15a-5p precursor to study the role of circFADS2 in miR-15a-5p maturation. Cell apoptosis was analyzed by cell apoptosis assay. RESULTS: CircFADS2 was upregulated in sepsis and inversely correlated with mature miR-15a-5p, but not miR-15a-5p precursor. In lung cells, circFADS2 overexpression decreased the level of mature miR-15a-5p, but not miR-15a-5p precursor. LPS treatment decreased miR-15a-5p expression and increased circFADS2 level. Cell apoptosis analysis showed that circFADS2 overexpression reduced miR-15a-5p overexpression-induced apoptosis of LPS-treated lung cells. CONCLUSIONS: CircFADS2 is upregulated in sepsis to suppress LPS-induced lung cell apoptosis by inhibiting miR-15a-5p maturation.

Occupational identity, job satisfaction and their effects on turnover intention among Chinese Paediatricians: a cross-sectional study.

BACKGROUND: This study contributes to research on the paediatrician shortage by examining occupational identity, job satisfaction and their effects on turnover intention among paediatricians in China. METHODS: A multi-stage stratified random sampling method was employed to conduct a questionnaire survey. Of the 4906 survey recipients, valid data were collected from 4198 of the respondents (85.6%). The participants were from seven geographic regions of China (south, central, north, east, northwest, southwest, and northeast). Paediatricians who volunteered and provided written informed consent participated. All variables including basic socio-demographics and work-related characteristics, occupational identity, job satisfaction and turnover intention were based on available literature, and measured on a 5- point Likert scale. Statistical methods such as exploratory factor analysis (EFA), descriptive analysis, common method bias, one-way ANOVA test, Pearson correlation analysis and mediation analysis were used. RESULTS: Significant differences were observed among the respondents in terms of turnover intention based on age, education level, marital status, region, the type and grade of practice setting, professional title, years in practise, workload, rest days, and monthly income. Occupational identity and job satisfaction were both negatively related to turnover intention, and occupational identity was positively correlated with job satisfaction (r1 = - 0.601, p < 0.01; r2 = - 0.605, p < 0.01). The results also showed that job satisfaction played a mediating role in the association between occupational identity and turnover intention among Chinese paediatricians. CONCLUSIONS: Work conditions, workload and salary are crucial factors of turnover intention among paediatricians in China. Therefore, we suggest that healthcare managers should increase investment in paediatrics, implement salary reforms and dedicate more attention to female and young paediatricians, thus reducing turnover intention among Chinese paediatricians.

Extracorporeal membrane oxygenation (ECMO) for critically ill patients with coronavirus disease 2019 (COVID-19): A retrospective cohort study.

PURPOSE: The role of extracorporeal membrane oxygenatio (ECMO) for rescue therapy of respiratory failure in critically ill coronavirus disease 2019 (COVID-19) patients remains controversial. We aimed to evaluate the clinical outcomes of ECMO in the treatment of COVID-19 compared with conventional ventilation support. METHODS: In this retrospective cohort study, data were collected on extremely critical patients with COVID-19 from January 2020 to March 2020 in intensive care unit of a hospital in charge by national rescue team in Wuhan, China, the epicenter of pandemic. Patients were classified into the ECMO group and the conventional ventilation non-ECMO group. Clinical characteristics, technical characteristics, laboratory results, mortality, and complications of the two groups were analyzed. RESULTS: 88 patients with extremely critical COVID-19 were screened; 34 received ECMO support and 31 received conventional ventilation support. Both groups had comparable characteristics at baseline in terms of age, gender, and comorbidities. Before ECMO or conventional therapy, patients in the two groups had sever acute respiratory distress syndrome with a mean partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2 /FiO2 ) ratio of 69.6 and 75.4, respectively. At the time of reporting, patients in the ECMO had significantly lower in-hospital mortality compared with the control group (58.8 vs. 93.5%, p = .001). CONCLUSION: ECMO is shown to decrease the mortality of extremely critical ill COVID-19 patients compared with the conventional treatment. Although complications occurred frequently, ECMO could still be a rescue therapy for the treatment of COVID-19 during the pandemic.

Prenatal diagnosis of Duchenne muscular dystrophy revealed a novel mosaic mutation in Dystrophin gene: a case report.

BACKGROUND: Duchenne muscular dystrophies (DMDs) are X-linked recessive neuromuscular disorders with malfunction or absence of the Dystrophin protein. Precise genetic diagnosis is critical for proper planning of patient care and treatment. In this study, we described a Chinese family with mosaic DMD mutations and discussed the best method for prenatal diagnosis and genetic counseling of X-linked familial disorders. METHODS: We investigated all variants of the whole dystrophin gene using multiple DNA samples isolated from the affected family and identified two variants of the DMD gene in a sick boy and two female carriers by targeted next generation sequencing (TNGS), Sanger sequencing, and haplotype analysis. RESULTS: We identified the hemizygous mutation c.6794delG (p.G2265Efs*6) of DMD in the sick boy, which was inherited from his mother. Unexpectedly, a novel heterozygous mutation c.6796delA (p.I2266Ffs*5) of the same gene, which was considered to be a de novo variant, was detected from his younger sister instead of his mother by Sanger sequencing. However, further NGS analysis of the mother and her amniotic fluid samples revealed that the mother carried a low-level mosaic c.6796delA mutation. CONCLUSIONS: We reported two different mutations of the DMD gene in two siblings, including the novel mutation c.6796delA (p.I2266Ffs*5) inherited from the asymptomatic mosaic-carrier mother. This finding has enriched the knowledge of the pathogenesis of DMD. If no mutation is detected in obligate carriers, the administration of intricate STR/NGS/Sanger analysis will provide new ideas on the prenatal diagnosis of DMD.

Effects of Bovine Lactoferrin on Rat Intestinal Epithelial Cells.

OBJECTIVE: To determine the effects of bovine lactoferrin (bLF) on cell viability, proliferation, and the protective roles in intestinal epithelial cells-6 (IEC-6) treated by lipopolysaccharide (LPS). METHODS: Cell viability and proliferation of IEC-6 were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Brdu assay separately. Cell cycle distribution was analyzed by flow cytometry. Inflammatory cytokines were analysed by real-time PCR and ELISA. Western blot was utilized to measure the level of MAPK and NF-κß nuclear translocation. RESULTS: Dose-dependent effects of bLF on cell viability and proliferation were observed in IEC-6 cells (both P < 0.05), especially at a dose of 100 µg/ml. The percentage of cells in the G2 and S phase was significantly higher than those of the control group (8.17 ±â€Š0.49% vs 4.72 ±â€Š0.55%, P < 0.01 and 12.75 ±â€Š0.33% vs 9.48 ±â€Š0.33%, P < 0.01, respectively). The mRNA level of IL-1ß, IL-6 and TNF-α was decreased by co-stimulation of bLF and LPS compared with the LPS treatments alone in IEC-6 cells (all P < 0.001). The secretion of IL-6 and TNF-α were also decreased by co-stimulation of bLF and LPS (both P < 0.01). Bovine lactoferrin treatment at dose of 100 µg/ml could inhibit the activation of MAPK/NF-κß signal pathway induced by LPS (both P < 0.001). CONCLUSIONS: Bovine lactoferrin could promote the cell viability and proliferation, and have anti-inflammatory effects via inhibition of the activation of MAPK and NF-κß nuclear translocation. Supplementation of formula with bLF may be beneficial in preventing NEC in preterm infants.

Bone marrow mesenchymal stem cells modified by angiogenin-1 promotes tissue repair in mice with oxygen-induced retinopathy of prematurity by promoting retinal stem cell proliferation and differentiation.

Retinopathy has become one of the major factors that lead to blindness worldwide. Although many clinical therapies are concerned about such disease, most of them focus on symptoms alleviation. In this study, we aim to investigate whether coculture retinal stem cells (RSCs) with bone marrow mesenchymal stem cells transfected with angiogenin-1 (Ang-1-BMSCs) affects the damaged retinal tissue of oxygen-induced retinopathy of prematurity (OIR-ROP) mice. After OIR-ROP mouse model establishment, Ang-1-BMSCs, RSCs, and OIR-ROP retinal tissues were cocultured in a a transwell chamber. RSCs proliferation and the expression of Ang-1, insulin-like growth factor-1 (IGF-1) in the supernatant of RSCs, as well as ß-tubulin and protein kinase C (PKC) expression were evaluated. Finally, the repair of OIR-ROP mice retinal tissues was observed by injecting Ang-1-BMSCs + RSCs. In the OIR-ROP mouse model, RSCs cocultured with OIR-ROP retinal tissues could be induced to differentiate into cells expressing ß-tubulin and PKC and promote the expression of Ang-1 and IGF-1. coculture of Ang-1-BMSCs further enhanced the proliferation and differentiation of RSCs by promoting the expression of Ang-1 and IGF-1. Coculture of RSCs + Ang-1-BMSCs induced differentiation of Ang-1-BMSCs through interaction among intercellular factors and restored the damaged retinal tissue of OIR-ROP mice. Collectively, our study provided evidence that coculture of Ang-1-BMSCs and RSCs could promote the proliferation and differentiation of RSCs and improve the treatment for the damaged retina tissue of OIR-ROP mice.

Antagonistic Effect of Cuscuta chinensis on a Rat Model with Unilateral Cryptorchidism.

BACKGROUND The aim of this study was to investigate the effect of Cuscuta chinensis Lam. on germ cell apoptosis in a rat model of unilateral cryptorchidism. MATERIAL AND METHODS Thirty male SD rats were randomly and equally divided into a control group, a model group, and a Cuscuta group (5.0 g/kg/d) (n=10). The rat model of unilateral cryptorchidism in the model and Cuscuta groups was established by removal of the right gubernaculum, while rats in the control group received no treatment. After modeling, rats in the Cuscuta chinensis group were intragastrically administered Cuscuta chinensis extract (5.0 g/kg/d), while rats in the control group and model group were administered an equal volume of normal saline. After 90 days, all the rats were sacrificed and the testicles were separated and weighed, followed by TUNEL staining to detect germ cell apoptosis, flow cytometry to measure JC-1, ROS, and MDA, and Western blot analysis to evaluate the expression of Bax, Bcl-2, and cleaved caspase3. RESULTS Ninety days after the operation, Cuscuta chinensis Lam significantly minimized the damage caused by modeling by increasing weight of testis, reducing the germ cell apoptosis, and enhancing the mitochondrial membrane potential of testicles, as shown by levels of JC-1, ROS, and MDA, as well as elevating the level of Bcl-2/Bax and reducing the level of cleaved caspase3 (P<0.05). CONCLUSIONS Treatment with Cuscuta chinensis Lam reduced the germ cell apoptosis in rats with unilateral cryptorchidism, which provides new insight for the development of cryptorchidism therapy in the future.