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.

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.

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.

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.

[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.

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.

[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.

[Mortality rate and cause of death in hospitalized neonates: an analysis of 480 cases].

OBJECTIVE: To investigate the mortality rate and the cause of death of hospitalized neonates. METHODS: The clinical data of 480 neonates who died between January 2008 and December 2014 were collected. The mortality rates of neonates with different gestational ages, birth weights, sexes, and ages in days were analyzed. The abnormal perinatal factors, cause of death, and death grade were summarized. RESULTS: Among the 41 910 hospitalized neonates, 480 (1.1%) died, and the mortality rates of preterm infants and full-term infants were 1.7% and 0.7%, respectively. The mortality rate of hospitalized neonates decreased from 1.4% in 2008 to 1.1% in 2014, and the decrease was more apparent in the preterm infants with a gestational age of <32 weeks and the neonates with a birth weight of <1 000 g. Among preterm infants and full-term infants, those with a lower gestational age tended to have a higher mortality rate, but post-term infants had an increased mortality rate. The infants with a lower birth weight tended to have a higher mortality rate. Male neonates had a significantly higher mortality rate than female neonates (1.31% vs 0.92%; P<0.05). Among the neonates who died, 61.3% had definite abnormal perinatal factors, including abnormal amniotic fluid (29.4%), premature rupture of membranes (16.9%), placental abnormality (16.9%), fetal intrauterine distress (14.0%), and abnormal umbilical cord (12.3%). Among the 480 neonates who died, 57 (11.9%) died within 24 hours after birth, 181 (37.7%) died within 2-7 days, and 242 (50.4%) died within 8-28 days. The three most common causes of death were infection, birth defect, and respiratory distress syndrome. The most common cause of death was respiratory distress syndrome in 2008-2011 and infection in 2012-2014. Respiratory distress syndrome was the most common cause of death in preterm infants with a gestational age of <32 weeks, neonates with a birth weight of <1 500 g, and neonates who died with 24 hours; infection was the most common cause of death in neonates with a gestational age of 32-42 weeks, neonates with a birth weight of 1 500-4 000 g, and neonates who died within 8-28 days. Neonatal asphyxia was the major cause of death in post-term infants. Inevitable deaths (grade 1) accounted for 54.4%, deaths that could be avoided under certain conditions (grade 2) accounted for 23.3%, and deaths caused by concerns about prognosis or economic reasons (grade 3) accounted for 22.3%. CONCLUSIONS: In recent years, the treatment of neonates has gradually improved, and the mortality rate of neonates is gradually decreasing, especially in neonates with low gestational age and birth weight. Important measures for reducing the mortality rate in neonates include enhancing perinatal management, reducing abnormal perinatal factors, preventing infection, and increasing parents' confidence in treatment.

Edaravone attenuates hippocampal damage in an infant mouse model of pneumococcal meningitis by reducing HMGB1 and iNOS expression via the Nrf2/HO-1 pathway.

AIM: Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a free radical scavenger that has shown potent antioxidant, anti-inflammatory and neuroprotective effects in variety of disease models. In this study, we investigated whether edaravone produced neuroprotective actions in an infant mouse model of pneumococcal meningitis. METHODS: C57BL/6 mice were infected on postnatal d 11 by intracisternal injection of a certain inoculum of Streptococcus pneumoniae. The mice received intracisternal injection of 10 µL of saline containing edaravone (3 mg/kg) once a day for 7 d. The severity of pneumococcal meningitis was assessed with a clinical score. In mice with severe meningitis, the survival rate from the time of infection to d 8 after infection was analyzed using Kaplan-Meier curves. In mice with mild meningitis, the CSF inflammation and cytokine levels in the hippocampus were analyzed d 7 after infection, and the clinical neurological deficit score was evaluated using a neurological scoring system d 14 after infection. The nuclear factor (erythroid-derived 2)-like 2 knockout (Nrf2 KO) mice and heme oxygenase-1 knockout (HO-1 KO) mice were used to confirm the involvement of Nrf2/HO-1 pathway in the neuroprotective actions of edaravone. RESULTS: In mice with severe meningitis, edaravone treatment significantly increased the survival rate (76.4%) compared with the meningitis model group (32.2%). In mice with mild meningitis, edaravone treatment significantly decreased the number of leukocytes and TNF- levels in CSF, as well as the neuronal apoptosis and protein levels of HMGB1 and iNOS in the hippocampus, but did not affect the high levels of IL-10 and IL-6 in the hippocampus. Moreover, edaravone treatment significantly improved the neurological function of mice with mild meningitis. In Nrf2 KO or HO-1 KO mice with the meningitis, edaravone treatment was no longer effective in improving the survival rate of the mice with severe meningitis (20.2% and 53.6%, respectively), nor it affected the protein levels of HMGB1 and iNOS in the hippocampus of the mice with mild meningitis. CONCLUSION: Edaravone produces neuroprotective actions in a mouse model of pneumococcal meningitis by reducing neuronal apoptosis and HMGB1 and iNOS expression in the hippocampus via the Nrf2/HO-1 pathway. Thus, edaravone may be a promising agent for the treatment of bacterial meningitis.

Treatment of neonates with meconium aspiration syndrome by proportional assist ventilation and synchronized intermittent mandatory ventilation: a comparison study.

BACKGROUND: This study aimed to compare the relevant clinical parameters of neonates with MAS who are supported by proportion assisted ventilation (PAV) and synchronized intermittent mandatory ventilation (SIMV). METHODS: Forty neonates diagnosed as MAS who required mechanical ventilation were divided randomly into PAV group and SIMV group (N.=20). The respiratory rate (RR), heart rate (HR), peak inspiratory pressure (PIP), mean arterial blood pressure (MABP), arterial-to-alveolar oxygen tension ratio (a/APO2), fraction of inspiration oxygen (FiO2), mean airway pressure (MAP) and tidal volume (VT) were measured before the ventilation, 1,12, 24, 48 hours after the ventilation and before weaning. RESULTS: We observed no significant differences in the mechanical ventilation time, oxygen supply time, hospital stay between PAV and SIMV groups. In addition, we found no significant differences in HR, MABP, a/APO2 and FiO2 at every time point between two groups (P>0.05). However, we observed significant differences in RR, MAP, PIP and VT at every time point between two groups (P<0.05). CONCLUSIONS: PAV and SIMV might be a useful ventilator mode to support the neonates with MAS who require ventilation. To achieve the same effect, PAV adopts rapid shallow breathing pattern, with smaller tidal volume and lower MAP and PIP.

A MCP-1 promoter polymorphism at G-2518A is associated with spontaneous preterm birth.

Monocyte chemoattractant protein-1 (MCP-1) is an important chemokine involved in the pathogenesis of spontaneous preterm birth (SPTB). We examined whether the MCP-1 G-2518A polymorphism is associated with the risk of SPTB in a Chinese population. The MCP-1 G-2518A polymorphism was genotyped in 569 preterm singleton neonates and in 673 term neonates using polymerase chain reaction-restriction fragment length polymorphism analysis. The distribution of the MCP-1 G-2518A genotype and the allele frequencies between the SPTB patients and the controls were not significantly different in the overall sample. However, we found that the AA genotype was associated with significantly increased susceptibility to very SPTB (<32 weeks) [odds ratio (OR) 2.07; 95 % confidence interval (CI), 1.27-3.36; P = 0.005) and extremely SPTB (<28 weeks) (OR 2.74; 95 % CI, 1.10-6.72; P = 0.014) compared with -2518G-positive genotypes (GG + GA genotypes). When extremely preterm neonates and very preterm neonates were combined, the AA genotype was also significantly associated with increased susceptibility to SPTB (OR 2.23; 95 % CI, 1.40-3.54; P < 0.001). The MCP-1 G-2518A polymorphism was not associated with increased susceptibility to SPTB in patients with premature rupture of the membranes (PROM) or in those without PROM. Our findings suggest that the MCP-1 G-2518A polymorphism may plays a role in mediating the susceptibility to SPTB in the Chinese population. Knowledge of genetic factors contributing to the pathogenesis of SPTB may have implications for screening and treatment of this disorder.

[Analysis of MLC1 gene mutation in a Chinese family with megalencephalic leukoencephalopathy with subcortical cysts].

The clinical data of a patient with megalencephalic leukoencephalopathy (MLC) with subcortical cysts and her parents were collected. MLC1 gene mutation was detected by polymerase chain reaction and direct DNA sequencing. The patient presented with motor developmental delay and giant skull, and brain magnetic resonance imaging showed diffuse white matter swelling accompanied by subcortical cysts in bilateral frontal and parietal lobes. Gene sequencing identified two heterozygous mutations of MLC1, including missense mutation in exon 3 (c.217G>A, p.Gly73Arg) and splice site mutation in intron 9 (c.772-1G>C in IVS9-1). The patient's parents both had heterozygous mutation c.772-1G>C in IVS9-1 with normal phenotype. It can be presumed that c.772-1G>C in IVS9-1 comes from the parents, and c.217G>A (p.Gly73Arg) is a de novo mutation.

[Detection of subtelomeric copy number variations in children with intellectual disability].

OBJECTIVE: To detect subtelomeric copy number variations in children with genetic intellectual disability (ID) using multiplex ligation-dependent probe amplification (MLPA), and to investigate the pathogenesis of genetic ID. METHODS: A total of 68 children with ID who had normal results of G-banding karyotype analysis were included in the study. Their subtelomeric copy number variations were detected using MLPA P036. RESULTS: Among the 68 children with ID, 7(10%) showed subtelomeric copy number variations, and all the variations were deletion mutations. Among them, 1 case carried 2 subtelomeric microdeletions, and 1 case carried 4 subtelomeric microdeletions. CONCLUSIONS: Subtelomeric copy number variations are important causes of genetic ID. MLPA can be used as an economic and effective method for investigating the pathogenesis of genetic ID.

[Clinical and imaging features of premature infants with different degrees of bronchopulmonary dysplasia].

OBJECTIVE: To study the clinical and imaging features of premature infants with different degrees of bronchopulmonary dysplasia (BPD). METHODS: A prospective study was performed on the clinical data of 59 premature infants (gestational age <32 weeks) with BPD. Among the 59 premature infants, 37 cases had mild BPD and the other 22 cases had moderate to severe BPD. The clinical and imaging data were compared between these premature infants with different degrees of BPD. RESULTS: The durations of mechanical ventilation, oxygen therapy, antibiotic therapy, parenteral nutrition, and hospitalization in the moderate to severe group were significantly longer than those in the mild group (P<0.05). The incidence of nosocomial infection and number of times of red blood cell transfusion in the moderate to severe group were significantly higher than that in the mild group. The rates of X-ray changes, including grade I respiratory distress syndrome (1 day after birth) and hypolucency of lungs (4-10 days and ≥ 28 days after birth) were significantly higher in the mild group than in the moderate to severe group. The rates of X-ray changes in classical BPD stage III (4-10 days after birth) and IV (≥ 28 days after birth) were significantly higher in the moderate to severe group than in the mild group. CONCLUSIONS: The durations of mechanical ventilation, oxygen therapy, and antibiotic therapy and the incidence of nosocomial infection are correlated with the severity of BPD. The premature infants with severer BPD need a longer duration of parenteral nutrition and more times of red blood cell transfusion and have more typical imaging changes of BPD. Imaging examination has a predictive value for the severity of BPD.

A novel silent deletion, an insertion mutation and a nonsense mutation in the TCOF1 gene found in two Chinese cases of Treacher Collins syndrome.

Treacher Collins syndrome (TCS) is the most common and well-known craniofacial disorder caused by mutations in the genes involved in pre-rRNA transcription, which include the TCOF1 gene. This study explored the role of TCOF1 mutations in Chinese patients with TCS. Mutational analysis of the TCOF1 gene was performed in three patients using polymerase chain reaction and direct sequencing. Among these three patients, two additional TCOF1 variations, a novel 18 bp deletion and a novel 1 bp insertion mutation, were found in patient 1, together with a novel nonsense mutation (p.Ser476X) and a previously reported 4 bp deletion (c.1872_1875delTGAG) in other patients. Pedigree analysis allowed for prediction of the character of the mutation, which was either pathological or not. The 18 bp deletion of six amino acids, Ser-Asp-Ser-Glu-Glu-Glu (798*803), which was located in the CKII phosphorylation site of treacle, seemed relatively benign for TCS. By contrast, another novel mutation of c.1072_1073insC (p.Gln358ProfsX23) was a frameshift mutation and expected to result in a premature stop codon. This study provides insights into the functional domain of treacle and illustrates the importance of clinical and family TCS screening for the interpretation of novel sequence alterations.

[Effects of recombinant human interleukin-11 on LPS-induced intestinal epithelial cell injury in rats].

OBJECTIVE: To study the effects of recombinant human interleukin-11 (rhIL-11) on the proliferation and apoptosis of rat intestinal epithelial cell line (IEC-6). METHODS: IEC-6 cells were treated with LPS to establish necrotizing enterocolitis (NEC) model in vitro. rhIL-11 (100 ng/mL) was administered following LPS treatment and these cells were used as the IL-11 treatment group. The cells treated with normal saline only served as the control group. MTT assay was used to determine an optimal concentration (5-200 µg/mL) and time (1-24 h). MTT assay was used to measure the proliferation of IEC-6 cells at 3, 6, 9 and 12 hours after rhIL-11 treatment. Flow cytometry was used to evaluate the apoptosis of IEC-6 cells. RESULTS: IEC-6 cells treated with various concentrations of LPS at various time points showed a lower proliferation than the control group (P<0.05). After 9 hours of rhIL-11 treatment, the proliferation activity of IEC-6 cells in the IL-11 treatment group significantly increased compared with the NEC model group without rhIL-11 treatment (P<0.05), reaching to the level of the control group. The total apoptotic and necrotic rate of IEC-6 cells in the IL-11 treatment group decreased significantly compared with the NEC model group without rhIL-11 treatment (P<0.01), but were still higher than the control group (P<0.05). CONCLUSIONS: rhIL-11 can promote proliferation and reduce apoptotic and necrotic rates of IEC-6 cells treated with LPS.

[Perinatal high-risk factors for necrotizing enterocolitis in preterm infants: a case-control study].

OBJECTIVE: To study the timing of presentation and perinatal high-risk factors for necrotizing enterocolitis (NEC) in preterm infants with a gestational age of <33 weeks. METHODS: A case-control study was conducted in 49 preterm infants with NEC (gestational age <33 weeks) who were admitted to the Neonatal Intensive Care Unit of Beijing Bayi Children's Hospital between October 1, 2010 and December 30, 2012, as well as preterm infants without NEC during the same period. The timing of presentation of NEC was retrospectively analyzed, and the perinatal high-risk factors for NEC were determined by multivariate logistic regression analysis. RESULTS: The median age of onset was 17.5 days (range: 3-106 d) in preterm infants with NEC. Sex, being small for gestational age, delivery mode and antenatal corticosteroid therapy were not associated with the development of NEC; low gestational age, low birth weight and neonatal asphyxia increased the risk of NEC, and low gestational age was identified as an independent high-risk factor for the development of NEC. CONCLUSIONS: Low gestational age is an important risk factor for the development NEC in preterm infants under 33 weeks' gestation, and the median age of onset is 17.5 days.

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.

Lipopolysaccharides shapes the human Wharton's jelly-derived mesenchymal stem cells in vitro.

BACKGROUND: Although the expression of toll-like receptors (TLRs) on different types of human mesenchymal stem cells (hMSCs) has recently been reported, controversy remains regarding the presence of TLR4 as well as its engagement and impact on human Wharton's jelly-derived MSCs (hWJ-MSCs). METHODS: In the present study, the expression and role of TLR4 in hWJ-MSCs was investigated using a model of lipopolysaccharide (LPS). Proliferation, apoptosis, and the expression of paracrine factors in hWJ-MSCs primed with LPS were analysed. RESULTS: The expression of TLR4 was high at the RNA level but very low at the protein level. hWJ-MSCs responded to LPS stimulation and initiated a marked up-regulation of inflammatory cytokine (IL-1α, IL-1ß, IL-6, and IL-8) production. Moreover, hWJ-MSCs LPS stimulation resulted in the up-regulation of indoleamine 2,3-dioxygenase [IDO]-1, Cox2, interferon [IFN]-ß, and matrix metalloproteinase (MMP)-2 but a down-regulation of MMP-9, which affect the immunosuppressive potential of hWJ-MSCs. CONCLUSIONS: These data suggest that LPS engagement shapes hWJ-MSCs and results in the production of pro-inflammatory cytokines and inhibitory immune mediators, showing TLR4 agonist induces the hWJ-MSCs polarization to a pro-inflammatory and immunosuppressive state, which may be beneficial for the exploration of the clinical potential of hWJ-MSCs.