Mesenchymal stem cells-based therapies for severe ARDS with ECMO: a review.

Acute respiratory distress syndrome (ARDS) is the primary cause of respiratory failure in critically ill patients. Despite remarkable therapeutic advances in recent years, ARDS remains a life-threatening clinical complication with high morbidity and mortality, especially during the global spread of the coronavirus disease 2019 (COVID-19) pandemic. Previous studies have demonstrated that mesenchymal stem cell (MSC)-based therapy is a potential alternative strategy for the treatment of refractory respiratory diseases including ARDS, while extracorporeal membrane oxygenation (ECMO) as the last resort treatment to sustain life can help improve the survival of ARDS patients. In recent years, several studies have explored the effects of ECMO combined with MSC-based therapies in the treatment of ARDS, and some of them have demonstrated that this combination can provide better therapeutic effects, while others have argued that some critical issues need to be solved before it can be applied to clinical practice. This review presents an overview of the current status, clinical challenges and future prospects of ECMO combined with MSCs in the treatment of ARDS.

Exploration of pathogenic microorganism within the small intestine of necrotizing enterocolitis.

BACKGROUND: Necrotizing enterocolitis (NEC) is the most common severe gastrointestinal emergency in neonates. We designed this study to identify the pathogenic microorganisms of NEC in the microbiota of the small intestine of neonates. METHODS: Using the 16S ribosomal DNA (rDNA) sequencing method, we compared and analyzed the structure and diversity of microbiotas in the intestinal feces of different groups of neonates: patients undergoing jejunostomy to treat NEC (NP group), neonates undergoing jejunostomy to treat other conditions (NN group), and neonates with NEC undergoing conservative treatment (NC group). We took intestinal feces and saliva samples from patients at different time points. RESULTS: The beta diversities of the NP, NN, and NC groups were all similar. When comparing the beta diversities between different time points in the NP group, we found similar beta diversities at time points E1 to E3 but significant differences between the E2-E3 and E4 time points: the abundances of Klebsiella and Enterococcus (Proteobacteria) were higher at the E1-E3 time points; the abundance of Escherichia-Shigella (Proteobacteria) increased at the E2 time point, and the abundance of Klebsiella decreased significantly, whereas that of Streptococcus increased significantly at the E4 time point. CONCLUSIONS: Our results suggest that the pathological changes of intestinal necrosis in the small intestine of infants with NEC are not directly caused by excessive proliferation of pathogenic bacteria in the small intestine. The sources of microbiota in the small intestine of neonates, especially in premature infants, may be affected by multiple factors.

Safety and immunogenicity of heterologous boosting with orally aerosolised or intramuscular Ad5-nCoV vaccine and homologous boosting with inactivated vaccines (BBIBP-CorV or CoronaVac) in children and adolescents: a randomised, open-label, parallel-controlled, non-inferiority, single-centre study.

BACKGROUND: Heterologous booster immunisation with orally administered aerosolised Ad5-nCoV vaccine (AAd5) has been shown to be safe and highly immunogenic in adults. Here, we aimed to assess the safety and immunogenicity of heterologous booster immunisation with orally administered AAd5 in children and adolescents aged 6-17 years who had received two doses of inactivated vaccine (BBIBP-CorV or CoronaVac). METHODS: We did a randomised, open-label, parallel-controlled, non-inferiority study to assess the safety and immunogenicity of heterologous booster immunisation with AAd5 (0·1 mL) or intramuscular Ad5-nCoV vaccine (IMAd5; 0·3 mL) and homologous booster immunisation with inactivated vaccine (BBIBP-CorV or CoronaVac; 0·5 mL) in children (aged 6-12 years) and adolescents (aged 13-17 years) who had received two doses of inactivated vaccine at least 3 months earlier in Hunan, China. Children and adolescents who were previously immunised with two-dose BBIBP-CorV or CoronaVac were recruited for eligibility screening at least 3 months after the second dose. A stratified block method was used for randomisation, and participants were stratified by age and randomly assigned (3:1:1) to receive AAd5, IMAd5, or inactivated vaccine. The study staff and participants were not masked to treatment allocation. Laboratory and statistical staff were masked during the study. In this interim analysis, adverse events within 14 days and geometric mean titre (GMT) of serum neutralising antibodies on day 28 after the booster vaccination, based on the per-protocol population, were used as the primary outcomes. The analysis of non-inferiority was based on comparison using a one-sided 97·5% CI with a non-inferiority margin of 0·67. This study was registered at ClinicalTrials.gov, NCT05330871, and is ongoing. FINDINGS: Between April 17 and May 28, 2022, 436 participants were screened and 360 were enrolled: 220 received AAd5, 70 received IMAd5, and 70 received inactivated vaccine. Within 14 days after booster vaccination, vaccine-related adverse reactions were reported: 35 adverse events (in 13 [12%] of 110 children and 22 [20%] of 110 adolescents) in 220 individuals in the AAd5 group, 35 (in 18 [51%] of 35 children and 17 [49%] of 35 adolescents) in 70 individuals in the IMAd5 group, and 13 (in five [14%] of 35 children and eight [23%] of 35 adolescents) in 70 individuals in the inactivated vaccine group. Solicited adverse reactions were also reported: 34 (13 [12%] of 110 children and 21 [10%] of 110 adolescents) in 220 individuals in the AAd5 group, 34 (17 [49%] of 35 children and 17 [49%] of 35 adolescents) in 70 individuals in the IMAd5 group, and 12 (five [14%] of 35 children and seven [20%] of 35 adolescents) in 70 individuals in the inactivated vaccine group. The GMTs of neutralising antibodies against ancestral SARS-CoV-2 Wuhan-Hu-1 (Pango lineage B) in the AAd5 group were significantly higher than the GMTs in the inactivated vaccine group (adjusted GMT ratio 10·2 [95% CI 8·0-13·1]; p<0·0001). INTERPRETATION: Our study shows that a heterologous booster with AAd5 is safe and highly immunogenic against ancestral SARS-CoV-2 Wuhan-Hu-1 in children and adolescents. FUNDING: National Key R&D Program of China.

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.

Cystic angiomatosis in children: clinical experience and review of literature.

BACKGROUND: Cystic angiomatosis is a rare benign disease manifesting as multiple lytic and sclerotic bone lesions, described as the proliferation of vascular and lymphatic channels lined by a single layer of endothelial cells. However, the potential pathogenetic mechanism of the disease still remains unknown. Here, we reported a case of cystic angiomatosis with multifocal bone lesion evaluated by whole exome sequencing. CASE DESCRIPTION: In this presentation, we reported a case of an 11-year-old boy with pain in his chest. Computed tomography (CT) revealed the multiple lytic of the bone in the ribs, clavicle, vertebra thoracalis, skull, mandibula, shoulder blade, etc. The blood test showed ALP to be 393U/L and VEGF to be 287.26 pg/ml. The patient was performed with an open biopsy in the ribs and was diagnosed with cystic angiomatosis. Besides, the whole exome sequencing reported the single-nucleotide substitutions in the coding region of BRIP1, CHEK2, GRM4, and MUC16. Then, the upregulated genes involved CASC15, CENPF, ABCA13, ALK, BLM, and FGFR3. CONCLUSIONS: In this article, we report a rare case of cystic angiomatosis in a child with abnormal VEGF and ALP reported by peripheral blood examination. The whole exome sequencing could provide the reference for the potential molecular mechanism in the diagnosis and treatment of cystic angiomatosis.

Phelan-McDermid Syndrome in Pediatric Patients With Novel Mutations: Genetic and Phenotypic Analyses.

Background: PhelanrMcDermid syndrome (PMS) is an uncommon autosomal dominant inherited developmental disorder. The main characteristics are hypotonia, intellectual disability, autism spectrum disorder, autism-like behaviors and tiny facial deformities. Most cases are caused by the deletion of the 22q13 genomic region, including the deletion of SHANK3. Methods: Genetic and phenotype evaluations of ten Chinese pediatric patients were performed. The clinical phenotypes and genetic testing results were collected statistically. We analyzed the deletion of the 22q13 genomic region and small mutations in SHANK3 (GRCh37/hg19) and performed parental genotype verification to determine whether it was related to the parents or was a novel mutation. Results: The age of the patients diagnosed with PMS ranged from 0 to 12 years old. Nine of the pediatric patients experienced Intellectual Disability, language motion development delay and hypotonia as prominent clinical features. One subject had autism, two subjects had abnormal electroencephalogram discharge and one subject was aborted after fetal diagnosis. Three patients had a SHANK3 mutation or deletion. All but the aborted fetuses had intellectual disability. Among the ten patients, a deletion in the 22q13 region occurred in seven patients, with the smallest being 60.6 kb and the largest being >5.5 Mb. Three patients had heterozygous mutations in the SHANK3 gene. Conclusion: All ten patients had novel mutations, and three of these were missense or frameshift mutations. For the first time reported, it is predicted that the amino acid termination code may appear before protein synthesis. The novel mutations we discovered provide a reference for clinical research and the diagnosis of PMS.

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.

Latency period of PROM at term and the risk of neonatal infectious diseases.

To find the risk of time thresholds of PROM for infectious diseases of term neonates. A multi-center prospective cohort study including pregnancies with PROM at term with a single fetus were conducted. Time thresholds of the duration from PROM to delivery were examined in 2-h increments to assess the rates of infectious neonatal diseases. 7019 pregnancies were included in the study. Neonatal pneumonia and sepsis were most frequent infectious diseases in neonates born from mother with PROM at term. Rates of early-onset pneumonia varied significantly when comparing length of time of PROM greater than 16 h vs. less than 16 h (for EOP in 3 days of life, adjusted OR 1.864, 95% CI 1.159 ~ 2.997, p = 0.010; for EOP in 7 days of life, adjusted OR 1.704, 95% CI 1.104 ~ 2.628, p = 0.016). Neonates born from mother of whom the length of time from PROM to delivery ≥ 16 h were at a higher risk of acquiring EOP.

The clinical value of ultrasonic cardiac output monitor in very-low birth-weight and extremely-low-birth-weight infants undergoing PDA ligation.

BACKGROUND: Cardiorespiratory instability occurs very often in very-low-birth-weight (VLBW) and extremely-low-birth-weight (ELBW) infants undergoing patent ductus arteriosus (PDA) ligation during the early postoperative period. This study aimed to investigate ultrasonic cardiac output monitor (USCOM) as a bedside tool by evaluating the hemodynamic changes in preterm infants following PDA ligation and assessing factors that may influence these changes. METHODS: This was a single-center prospective observational study at a third-level neonatal intensive care unit. A total of 33 infants, including 21 VLBW and 12 ELBW infants, were involved. Hemodynamic measurements were performed in these infants using a USCOM preoperatively as well as 0-1 h, 8-10 h, and 24 h postoperatively. RESULTS: The PDA ligation was associated with reductions of the left ventricular cardiac output (LVCO) (P < 0.001), cardiac index (P < 0.001), flow time corrected (FTC) (P < 0.001), Smith-Madigan inotropy index (SMII) (P < 0.001), oxygen delivery (DO2) (P < 0.001), and oxygen delivery index (DO2I) (P < 0.001) and an increase of the systemic vascular resistance index (SVRI) (P < 0.001) at 0-1 h, 8-10 h, and 24 h post-ligation compared with the respective preoperative values. Compared with the respective values at 0-1 h post-ligation, there was no significant difference in the CI, SMII, or FTC at 8-10 h and 24 h post-ligation. However, the SVRI decreased at 8-10 h and 24 h post-ligation. Moreover, the DO2I increased at 8-10 h and 24 h post-ligation, and the LVCO and DO2 increased at 24 h post-ligation. CONCLUSION: Our study confirmed that the hemodynamic changes measured by the USCOM were similar to those measured by echocardiography in previous reports. Thus, USCOM is a useful and convenient bedside tool for assessing hemodynamic changes to guide the use of fluids, inotropic agents, and vasopressors and help modify the post-ligation course, and they may be a surrogate for repeated echocardiography during the early post-ligation period in preterm infants or a preliminary screening method.

The implications of an integrated management model of prenatal diagnosis/postnatal treatment for premature infants with critical congenital heart disease-a case-control study.

Background: The high death rate and medical costs of critical congenital heart disease (CCHD) in preterm infants has resulted in significant burdens on both countries and individuals. It is unclear how this affects the mortality of the integrated management model of prenatal diagnosis/postnatal treatment. This study explored the effects of the delivery classification scale for fetal heart and postnatal infants' CCHD on prenatal and postnatal integrated treatment strategies to improve the effectiveness of disease management in CCHD. Methods: This study was a case-control study, which retrospectively analyzed the clinical data of 79 preterm infants (<37 weeks) who underwent prenatal diagnosis and postpartum treatment in Guangdong Provincial People' s Hospital (China) from June 2017 to June 2019. According to the diagnostic and exclusion criteria, the subjects were divided into prenatal and postpartum diagnostic groups. The clinical characteristics and survival outcomes of patients were collected and compared. The delivery classification scale was used for risk stratification and patient management. Results: Among the 79 patients included in this study, 48 (60.76%) were diagnosed prenatally, and 31 (39.24%) were diagnosed postpartum. The prenatal diagnosis group was born slightly earlier during the gestation period [35.00 (33.29-35.86) vs. 35.57 (34.14-36.71) weeks, P<0.05], and their mothers were older (33.23±5.22 vs. 30.43±6.37 years, P<0.05). The difference in the admission age between the groups was statistically significant [0 (0-5.5) vs. 7 (5-16) days, P<0.001]. The median survival time of the prenatal diagnosis group was higher than the postnatal diagnosis group [48 months (95% CI: 40.78-57.29) vs. 39 months (95% CI: 34.41-44.32), P<0.05]. The 3-year survival rates of the classes I, II, and III were 92.31% (12/13), 59.09% (13/22), and 38.46% (5/13), respectively. The survival of class I as denoted in the delivery classification scale was better than classes II or III (class I vs. II, P<0.05; class I vs. III, P<0.05). Unexpectedly, the hospitalisation costs were lower and total in-hospital days were shorter in the postnatal diagnosis group. Conclusions: The results indicated that the integrated management of a prenatal diagnosis/postnatal treatment approach in premature infants may be effective. Furthermore, the delivery classification scale has a particular prognostic value for CCHD. The authors anticipate that their management model will be able to contribute to the shift from a reactive monodisciplinary system to a proactive, multidisciplinary and dynamic management paradigm in premature infants with CCHD in the near future.

The value of oxygen index and base excess in predicting the outcome of neonatal acute respiratory distress syndrome

Abstract Objective This study aimed to identify the predictors and threshold of failure in neonatal acute respiratory distress syndrome. Methods Newborns with severe acute respiratory distress syndrome aged 0-28 days and gestational age ≥36 weeks were included in the study if their cases were managed with non-extra corporal membrane oxygenation treatments. Patients were divided into two groups according to whether they died before discharge. Predictors of non-extra corporal membrane oxygenation treatment failure were sought, and the threshold of predictors was calculated. Results A total of 103 patients were included in the study. A total of 77 (74.8%) survived hospitalization and were discharged, whereas 26 (25.2%) died. Receiver operating characteristic analysis of oxygen index, pH, base excess, and combinations of these indicators demonstrated the advantage of the combination of oxygen index and base excess over the others variables regarding their predictive ability. The area under the curve for the combination of oxygen index and base excess was 0.865. When the cut-off values of oxygen index and base excess were 30.0 and −7.4, respectively, the sensitivity and specificity for predicting death were 77.0% and 84.0%, respectively. The model with base excess added a net reclassification improvement of 0.090 to the model without base excess. Conclusion The combination of oxygen index and base excess can be used as a predictor of outcomes in neonates receiving non-extra corporal membrane oxygenation treatment for acute respiratory distress syndrome. In neonates with acute respiratory distress syndrome, if oxygen index >30 and base excess <−7.4, non-extra corporal membrane oxygenation therapy is likely to lead to death.

The value of oxygen index and base excess in predicting the outcome of neonatal acute respiratory distress syndrome.

OBJECTIVE: This study aimed to identify the predictors and threshold of failure in neonatal acute respiratory distress syndrome. METHODS: Newborns with severe acute respiratory distress syndrome aged 0-28 days and gestational age ≥36 weeks were included in the study if their cases were managed with non-extra corporal membrane oxygenation treatments. Patients were divided into two groups according to whether they died before discharge. Predictors of non-extra corporal membrane oxygenation treatment failure were sought, and the threshold of predictors was calculated. RESULTS: A total of 103 patients were included in the study. A total of 77 (74.8%) survived hospitalization and were discharged, whereas 26 (25.2%) died. Receiver operating characteristic analysis of oxygen index, pH, base excess, and combinations of these indicators demonstrated the advantage of the combination of oxygen index and base excess over the others variables regarding their predictive ability. The area under the curve for the combination of oxygen index and base excess was 0.865. When the cut-off values of oxygen index and base excess were 30.0 and -7.4, respectively, the sensitivity and specificity for predicting death were 77.0% and 84.0%, respectively. The model with base excess added a net reclassification improvement of 0.090 to the model without base excess. CONCLUSION: The combination of oxygen index and base excess can be used as a predictor of outcomes in neonates receiving non-extra corporal membrane oxygenation treatment for acute respiratory distress syndrome. In neonates with acute respiratory distress syndrome, if oxygen index >30 and base excess <-7.4, non-extra corporal membrane oxygenation therapy is likely to lead to death.

Role of three tick species in the maintenance and transmission of Severe Fever with Thrombocytopenia Syndrome Virus.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel phlebovirus in the Bunyaviridae family, causing SFTS with high mortality rate. Haemaphysalis longicornis ticks has been demonstrated as a competent vector of SFTSV by experimental transmission study and field study. However, there has been query whether other tick species that infest human beings in the SFTS endemic regions are capable of transmitting the pathogen. Here by performing experimental transmission study, we compared the capable of transmitting SFTSV among Ixodes sinensis, Ixodes persulcatus and Dermacentor silvarum ticks. The transovarial transmission was seen in the I. sinensis ticks with a rate of 40%, but neither in I. persulcatus nor in D. silvarum ticks. I. sinensis ticks also have the ability to transmit SFTSV horizontally to uninfected mice at 7 days after feeding, but not for I. persalcatus or D. silvarum ticks. In the transstadial transmission of I. persulcatus and D. silvarum ticks, I. persulcatus ticks were tested negative from larvae to adults. But the D. silvarum ticks were tested positive from larvae to nymphs, with the positive rate of 100% (10/10) for engorged larval ticks and 81.25% (13/16) for molted nymphs. However, the mice bitten by SFTSV-infected D. silvarum nymphs were negative for SFTSV detection. Therefore, there is not enough evidence to prove the transstadial transmission of SFTSV in I. persalcatus and D. silvarum ticks.

Gene-Focused Networks Underlying Phenotypic Convergence in a Systematically Phenotyped Cohort With Heterogeneous Intellectual Disability.

The broad spectrum of intellectual disability (ID) patients' clinical manifestations, the heterogeneity of ID genetic variation, and the diversity of the phenotypic variation represent major challenges for ID diagnosis. By exploiting a manually curated systematic phenotyping cohort of 3803 patients harboring ID, we identified 704 pathogenic genes, 3848 pathogenic sites, and 2075 standard phenotypes for underlying molecular perturbations and their phenotypic impact. We found the positive correlation between the number of phenotypes and that of patients that revealed their extreme heterogeneities, and the relative contribution of multiple determinants to the heterogeneity of ID phenotypes. Nevertheless, despite the extreme heterogeneity in phenotypes, the ID genes had a specific bias of mutation types, and the top 44 genes that ranked by the number of patients accounted for 39.9% of total patients. More interesting, enriched co-occurrent phenotypes and co-occurrent phenotype networks for each gene had the potential for prioritizing ID genes, further exhibited the convergences of ID phenotypes. Then we established a predictor called IDpred using machine learning methods for ID pathogenic genes prediction. Using10-fold cross-validation, our evaluation shows remarkable AUC values for IDpred (auc = 0.978), demonstrating the robustness and reliability of our tool. Besides, we built the most comprehensive database of ID phenotyped cohort to date: IDminer http://218.4.234.74:3100/IDminer/, which included the curated ID data and integrated IDpred tool for both clinical and experimental researchers. The IDminer serves as an important resource and user-friendly interface to help researchers investigate ID data, and provide important implications for the diagnosis and pathogenesis of developmental disorders of cognition.

The correlation between prelabour rupture of the membranes and neonatal infectious diseases, and the evaluation of guideline implementation in China: a multi-centre prospective cohort study.

BACKGROUND: The aim of this study was to describe the epidemiology of prelabour rupture of membranes (PROM) in China and to assess the association between clinical practice following the guidelines and early neonatal infections. METHODS: We conducted a prospective cohort study of 15926 deliveries in ShenZhen Baoan Women's and Children's Hospital, Xibei Women's and Children's Hospital and Chengdu Women's and Children's Hospital between August 1, 2017, to March 31, 2018. Clinical data were collected for each participant. The epidemiology of PROM was described. The association between PROM with early neonatal infectious outcomes and the influence of the implementation of the guideline on early neonatal infectious outcomes were assessed. FINDINGS: The incidence of PROM was 18•7%. PROM was showed to be a risk factor for neonatal infectious diseases (adjusted OR 1•92, 95%CI 1•49~2•49, p<0•0001), early-onset pneumonia (EOP) (adjusted OR 1•81, 95%CI 1•29~2•53, p=0•0006) and early-onset sepsis(EOS) (adjusted OR 14•56, 95%CI 1•90~111•67, p=0•01) for term neonates. For term neonates born from mother with PROM, induction of labor according to the guideline was a protective factor for neonatal diseases(adjusted OR 0•50, 95%CI 0•25~1•00, p=0•00498) and EOP(adjusted OR 0•32, 95%CI 0•11~0•91, p=0•03). For preterm neonates born from mother with PROM, using antibiotics according to the guideline showed to be protective for neonatal infectious diseases (adjusted OR 0•14, 95%CI 0•09~0•23, p<0•0001) and EOP (adjusted OR 0•08, 95%CI 0•04~0•14, p<0•0001). INTERPRETATION: Our study showed the risk of PROM for infectious diseases (including EOP and EOS) and the benefit of the usage of antibiotics according to the guideline for infectious diseases and EOP for preterm neonates. FUNDING: National Natural Science Foundation of China, Capital Medical Development Research Fund of Beijing.

[Clinical effect of white noise combined with glucose in reducing the pain of retinopathy screening in preterm infants].

OBJECTIVE: To study the clinical effect of white noise combined with glucose in reducing the procedural pain of retinopathy screening in preterm infants. METHODS: A total of 396 preterm infants with a gestational age of 28-34 weeks and a birth weight of ≤2 000 g were randomly divided into 4 groups according to the intervention method for reducing pain in retinopathy screening: control group with 100 infants (no white noise or glucose intervention), white noise group with 96 infants, glucose group with 98 infants and white noise + glucose group with 102 infants. The Premature Infant Pain Profile (PIPP) was used to determine pain score during retinopathy screening, and the four groups were compared in terms of PIPP score before and after retinopathy screening. RESULTS: There were no significant differences in PIPP score, heart rate and blood oxygen saturation between the four groups at 3 minutes before screening (P>0.05). At 1 and 5 minutes after screening, the white noise, glucose and white noise + glucose groups had significantly lower heart rate and PIPP score but significantly higher blood oxygen saturation than the control group (P<0.05).The white noise + glucose group had significantly lower heart rate and PIPP score but significantly higher blood oxygen saturation than the white noise and glucose groups (P<0.05). CONCLUSIONS: White noise combined with glucose can reduce the procedural pain of retionopathy screening and keep vital signs stable 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.

[A review on neonatal acute respiratory distress syndrome].

Acute respiratory distress syndrome (ARDS) is a common clinical critical disease and is one of the main causes of death and disability in neonates. The etiology and pathogenesis of neonatal ARDS are complicated. It is an acute pulmonary inflammatory disease caused by the lack of pulmonary surfactant (PS) related to various pathological factors. It is difficult to distinguish neonatal ARDS from other diseases. At present, there is no specific treatment method for this disease. Respiratory support, PS replacement, extracorporeal membrane oxygenation, nutrition support and liquid management are main treatment strategies. This paper reviews the research advance in etiology, clinical characteristics, diagnosis and treatment strategies of neonatal ARDS.

Two novel L2HGDH mutations identified in a rare Chinese family with L-2-hydroxyglutaric aciduria.

BACKGROUND: L-2-Hydroxyglutaric aciduria (L-2-HGA) is a rare organic aciduria neurometabolic disease that is inherited as an autosomal recessive mode and have a variety of symptoms, such as psychomotor developmental retardation, epilepsy, cerebral symptoms as well as increased concentrations of 2-hydroxyglutarate (2-HG) in the plasma, urine and cerebrospinal fluid. The causative gene of L-2-HGA is L-2-hydroxyglutarate dehydrogenase gene (L2HGDH), which consists of 10 exons. CASE PRESENTATION: We presented a rare patient primary diagnosis of L-2-HGA based on the clinical symptoms, magnetic resonance imaging (MRI), and gas chromatography-mass spectrometry (GC-MS) results. Mutational analysis of the L2HGDH gene was performed on the L-2-HGA patient and his parents, which revealed two novel mutations in exon 3: a homozygous missense mutation (c.407 A > G, p.K136R) in both the maternal and paternal allele, and a heterozygous frameshift mutation [c.407 A > G, c.408 del G], (p.K136SfsX3) in the paternal allele. The mutation site p.K136R of the protein was located in the pocket of the FAD/NAD(P)-binding domain and predicted to be pathogenic. CONCLUSION: We predicted the homozygous missense mutation (c.407 A > G, p.K136R) was considered as the pathogenic mutation of the patient. The study highlights the power of pedigree analysis in order to interpret novel mutations.