Proteomic analysis reveals potential therapeutic targets for childhood asthma through Mendelian randomization.

BACKGROUND: Asthma is the most common chronic disease among children and poses a significant threat to their health. This study aims to assess the relationship between various plasma proteins and childhood asthma, thereby identifying potential therapeutic targets. METHODS: Based on publicly available genome-wide association study summary statistics, we employed a two-sample Mendelian randomization (MR) approach to elucidate the causal relationship between plasma proteins and asthma. Mediation analysis was then conducted to evaluate the indirect influence of plasma proteins on childhood asthma mediated through risk factors. Comprehensive analysis was also conducted to explore the association between plasma proteins and various phenotypes using the UK Biobank dataset. RESULTS: MR analysis uncovered a causal relationship between 10 plasma proteins and childhood asthma. Elevated levels of seven proteins (TLR4, UBP25, CBR1, Rac GTPase-activating protein 1 [RGAP1], IL-21, MICB, and PDE4D) and decreased levels of three proteins (GSTO1, LIRB4 and PIGF) were associated with an increased risk of childhood asthma. Our findings further validated the connections between reported risk factors (body mass index, mood swings, hay fever or allergic rhinitis, and eczema or dermatitis) and childhood asthma. Mediation analysis revealed the influence of proteins on childhood asthma outcomes through risk factors. Furthermore, the MR analysis identified 73 plasma proteins that exhibited causal associations with at least one risk factor for childhood asthma. Among them, RGAP1 mediates a significant proportion (25.10%) of the risk of childhood asthma through eczema or dermatitis. Finally, a phenotype-wide association study based on these 10 proteins and 1403 diseases provided novel associations between these biomarkers and multiple phenotypes. CONCLUSION: Our study comprehensively investigated the causal relationship between plasma proteins and childhood asthma, providing novel insights into potential therapeutic targets.

Effect of different courses and durations of invasive mechanical ventilation on respiratory outcomes in very low birth weight infants.

This multicenter retrospective study was conducted to explore the effects of different courses and durations of invasive mechanical ventilation (MV) on the respiratory outcomes of very low birth weight infants (VLBWI) in China. The population for this study consisted of infants with birth weight less than 1500 g needing at least 1 course of invasive MV and admitted to the neonatal intensive care units affiliated with the Chinese Neonatal Network within 6 h of life from January 1st, 2019 to December 31st, 2020. Univariate and multivariate logistic regression analyses were performed to evaluate associations between invasive MV and respiratory outcomes. Adjusted odds ratios (ORs) were computed with the effects of potential confounders. (1) Among the 3183 VLBWs with a history of at least one course of invasive MV, 3155 (99.1%) met inclusion criteria and were assessed for the primary outcome. Most infants received one course (76.8%) and a shorter duration of invasive MV (62.16% with ventilation for 7 days or less). (2) In terms of the incidence of all bronchopulmonary dysplasia (BPD) (mild, moderate, and severe BPD), there were no significant differences between different invasive MV courses [For 2 courses, adjusted OR = 1.11 (0.88, 1.39); For 3 courses or more, adjusted OR = 1.07 (0.72, 1.60)]. But, with the duration of invasive MV prolonging, the OR of BPD increased [8-21 days, adjusted OR = 1.98 (1.59, 2.45); 22-35 days, adjusted OR = 4.37 (3.17, 6.03); ≥ 36 days, adjusted OR = 18.44 (10.98, 30.99)]. Concerning severe BPD, the OR increased not only with the course of invasive MV but also with the duration of invasive MV [For 2 courses, adjusted OR = 2.17 (1.07, 4.40); For 3 courses or more, adjusted OR = 2.59 (1.02, 6.61). 8-21 days, adjusted OR = 8.42 (3.22, 22.01); 22-35 days, adjusted OR = 27.82 (9.08, 85.22); ≥ 36 days, adjusted OR = 616.45 (195.79, > 999.999)]. (3) When the interaction effect between invasive MV duration and invasive MV course was considered, it was found that there were no interactive effects in BPD and severe BPD. Greater than or equal to three courses would increase the chance of severe BPD, death, and the requirement of home oxygen therapy. Compared with distinct courses of invasive MV, a longer duration of invasive MV (> 7 days) has a greater effect on the risk of BPD, severe BPD, death, and the requirement of home oxygen therapy.

Reperfusion after hypoxia-ischemia exacerbates brain injury with compensatory activation of the anti- ferroptosis system: based on a novel rat model.

Hypoxic-ischemic encephalopathy, which predisposes to neonatal death and neurological sequelae, has a high morbidity, but there is still a lack of effective prevention and treatment in clinical practice. To better understand the pathophysiological mechanism underlying hypoxic-ischemic encephalopathy, in this study we compared hypoxic-ischemic reperfusion brain injury and simple hypoxic-ischemic brain injury in neonatal rats. First, based on the conventional Rice-Vannucci model of hypoxic-ischemic encephalopathy, we established a rat model of hypoxic-ischemic reperfusion brain injury by creating a common carotid artery muscle bridge. Then we performed tandem mass tag-based proteomic analysis to identify differentially expressed proteins between the hypoxic-ischemic reperfusion brain injury model and the conventional Rice-Vannucci model and found that the majority were mitochondrial proteins. We also performed transmission electron microscopy and found typical characteristics of ferroptosis, including mitochondrial shrinkage, ruptured mitochondrial membranes, and reduced or absent mitochondrial cristae. Further, both rat models showed high levels of glial fibrillary acidic protein and low levels of myelin basic protein, which are biological indicators of hypoxic-ischemic brain injury and indicate similar degrees of damage. Finally, we found that ferroptosis-related Ferritin (Fth1) and glutathione peroxidase 4 were expressed at higher levels in the brain tissue of rats with hypoxic-ischemic reperfusion brain injury than in rats with simple hypoxic-ischemic brain injury. Based on these results, it appears that the rat model of hypoxic-ischemic reperfusion brain injury is more closely related to the pathophysiology of clinical reperfusion. Reperfusion not only aggravates hypoxic-ischemic brain injury but also activates the anti-ferroptosis system.

Chlorogenic acid alleviates hypoxic-ischemic brain injury in neonatal mice.

Recent studies have shown that chlorogenic acid (CGA), which is present in coffee, has protective effects on the nervous system. However, its role in neonatal hypoxic-ischemic brain injury remains unclear. In this study, we established a newborn mouse model of hypoxic-ischemic brain injury using a modified Rice-Vannucci method and performed intraperitoneal injection of CGA. We found that CGA intervention effectively reduced the volume of cerebral infarct, alleviated cerebral edema, restored brain tissue structure after injury, and promoted axon growth in injured brain tissue. Moreover, CGA pretreatment alleviated oxygen-glucose deprivation damage of primary neurons and promoted neuron survival. In addition, changes in ferroptosis-related proteins caused by hypoxic-ischemic brain injury were partially reversed by CGA. Furthermore, CGA intervention upregulated the expression of the key ferroptosis factor glutathione peroxidase 4 and its upstream glutamate/cystine antiporter related factors SLC7A11 and SLC3A2. In summary, our findings reveal that CGA alleviates hypoxic-ischemic brain injury in neonatal mice by reducing ferroptosis, providing new ideas for the treatment of neonatal hypoxic-ischemic brain injury.

Value of metagenomic next-generation sequencing in children with severe infectious diseases. / å®åŸºå› ç»„äºŒä»£æµ‹åºåœ¨å„¿ç«¥é‡ç—‡æ„ŸæŸ“ä¸­çš„åº”ç”¨ä»·å€¼.

OBJECTIVES: To study the application value of metagenomic next-generation sequencing (mNGS) in children with severe infectious diseases. METHODS: An analysis was performed on the clinical data and laboratory test results of 29 children with severe infection who were admitted to the Second Affiliated Hospital of Wenzhou Medical University from June 2018 to December 2020. Conventional pathogen culture was performed for the 29 specimens (27 peripheral blood specimens and 2 pleural effusion specimens) from the 29 children, and mNGS pathogen detection was performed at the same time. RESULTS: Among the 29 children, 2 tested positive by conventional pathogen culture with 2 strains of pathogen, and the detection rate was 7% (2/29); however, 20 children tested positive by mNGS with 38 strains of pathogen, and the detection rate was 69% (20/29). The pathogen detection rate of mNGS was significantly higher than that of conventional pathogen culture (P<0.05), and mNGS could detect the viruses, fungi, and other special pathogens that conventional pathogen culture failed to detect, such as Orientia tsutsugamushi. The univariate analysis showed that gender, routine blood test results, C-reactive protein, procalcitonin, D-dimer, radiological findings, and whether antibiotics were used before admission did not affect the results of mNGS (P>0.05). CONCLUSIONS: Compared with conventional pathogen culture, mNGS is more sensitive for pathogen detection, with fewer interference factors. Therefore, it is a better pathogenic diagnosis method for severe infectious diseases in children.

Soluble Triggering Receptors Expressed on Myeloid Cells-1 as a Neonatal Ventilator-Associated Pneumonia Biomarker.

BACKGROUND: Neonatal ventilator-associated pneumonia (NVAP) is one of the main infections acquired in hospitals, and soluble triggering receptors expressed on myeloid cells-1 (sTREM-1) are a TREM-1 subtype that can be released into the blood or bodily fluids during an infection. METHODS: The patients included in the present study were divided into three groups: the NVAP group, the first control group, and the second control group (n = 20, each). Children requiring respiratory treatment were assigned to the NVAP group, newborns who received mechanical ventilation and had neonatal respiratory distress syndrome were assigned to the first control group, and newborns with normal X-ray and electrocardiogram results but no non-pulmonary infection was assigned to the second control group. The blood and bronchoalveolar lavage fluid (BALF) sTREM-1 levels in all newborns were analyzed. RESULTS: The acute-phase blood and BALF sTREM-1 levels were significantly higher in the NVAP group than in the first control group, and the blood sTREM-1 expression level was lower in the second control group than in the NVAP group. CONCLUSION: The present results suggest that sTREM-1 might be a useful biomarker for NVAP prediction in the Department of Pediatrics.

Neferine Protects against Hypoxic-Ischemic Brain Damage in Neonatal Rats by Suppressing NLRP3-Mediated Inflammasome Activation.

Hypoxic-ischemic encephalopathy (HIE) is recognized as the main cause of neonatal death, and efficient treatment strategies remain limited. Given the prevalence of HIE and the associated fatality, further studies on its pathogenesis are warranted. Oxidative stress and neuroinflammatory injury are two important factors leading to brain tissue injury and nerve cell loss in HIE. Neferine, an alkaloid extracted from lotus seed embryo, exerts considerable effects against several diseases such as cancers and myocardial injury. In this study, we demonstrated the neuroprotective effect of neferine on HIE and hypothesized that it involves the inhibition of neuronal pyroptosis, thereby ameliorating neurological inflammation and oxidative stress. We demonstrated that the mRNA levels of proteins associated with pyroptosis including caspase-1, the caspase adaptor ASC, gasdermin D, interleukin- (IL-) 18, IL-1ß, and some inflammatory factors were significantly increased in neonatal HIBD model rats compared to those in the control group. The increase in these factors was significantly suppressed by treatment with neferine. We stimulated PC12 cells with CoCl2 to induce neuronal HIBD in vitro and investigated the relationship between neferine and pyroptosis by altering the expression of the NLRP3 inflammasome. The overexpression of NLRP3 partially reversed the neuroprotective effect of neferine on HIBD, whereas NLRP3 knockdown further inhibited caspase-1 activation and IL-1ß and IL18 expression. In addition, simultaneous alteration of NLRP3 expression induced changes in intracellular oxidative stress levels after HIBD. These findings indicate that neferine ameliorates neuroinflammation and oxidative stress injury by inhibiting pyroptosis after HIBD. Our study provides valuable information for future studies on neferine with respect to neuroinflammation and pyroptosis.

The Effects of Early Oropharyngeal Administration of Microdosed Colostrum on Feeding Status in Ventilated Extremely Low-Birth-Weight Infants.

Background: For extremely low-birth-weight infants (ELBWIs), mechanical ventilation and total parenteral nutrition are generally required in the early stages and lose the protective effect of early gastrointestinal nutrition of colostrum. We conducted a prospective randomized controlled trial to explore the effectiveness of early colostrum oropharyngeal administration on the feeding status of ELBWIs on mechanical ventilation. Materials and Methods: We randomly divided mechanically ventilated ELBWIs into an intervention group and a control group. In the intervention group, we provided oropharyngeal administration of colostrum during mechanical ventilation. The first colostrum oropharyngeal administration ended within 24 hours of birth. In the control group, we gave colostrum only for gastrointestinal nutrition, and other interventions were the same as for the intervention group. We collected the 1st and 6th day of life airway secretions and urine specimens from both groups. We recorded feeding status, including corrected gestational age at onset of enteral nutrition, corrected gestational age of no gastric retention during feeding, corrected gestational age of full enteral nutrition, corrected gestational age of sucking began, and corrected gestational age of per oral feeding. We also recorded growth of body mass, the incidence of feeding intolerance, and necrotizing enterocolitis (NEC). Results: On the 6th day of life, concentrations of secretory immunoglobulin A, and lactoferrin in airway secretions and urine of the intervention group were significantly higher than those of the control group (p < 0.05). The intervention group showed younger corrected gestational age of no gastric retention during feeding, corrected gestational age of full enteral nutrition, the corrected gestational age of sucking began and per oral feeding than those in the control group (p < 0.05). The day of recovery to birth weight was earlier than those in the control group (p < 0.05). The rate of feeding intolerance and NEC incidence in the intervention group was significantly lower than in the control group (p < 0.05). Conclusions: Early oropharyngeal administration of colostrum improves immune function of the gastrointestinal tract and the systemic anti-infective capability in ELBWI on mechanical ventilation, promoting the maturity of gastrointestinal function, improving feeding condition, and reducing the risk of feeding intolerance and NEC.

LXA4 protects against hypoxic-ischemic damage in neonatal rats by reducing the inflammatory response via the IκB/NF-κB pathway.

Hypoxia and the resultant decreases in cerebral blood flow in the perinatal period can lead to neonatal hypoxic-ischemic (HI) brain injury, which can, in turn, cause severe disability or even death. However, the efficacy of current treatment strategies remains limited. Several studies have demonstrated that lipoxin A4 (LXA4), as one of the earliest types of endogenous lipid mediators, can inhibit the accumulation of neutrophils, arrest inflammation, and promote the resolution of inflammation. However, research on LXA4 in the nervous system has rarely been carried out. In the present study, we sought to investigate the protective effect of LXA4 on HI brain damage in neonatal rats, as well as the underlying mechanisms. Through experiments conducted using an HI animal model, we found that the LXA4 intervention promoted the recovery of neuronal function and tissue structure following brain injury while maintaining the integrity of the blood-brain barrier in addition to reducing cerebral edema, infarct volume, and inflammatory responses. Our results suggest that LXA4 interfered with neuronal oxygen-glucose deprivation insults, reduced the expression of inflammatory factors, inhibited apoptosis, and promoted neuronal survival in vitro. Finally, the LXA4 intervention attenuated HI-induced activation of inhibitor kappa B (IκB) and degradation of nuclear factor-κB (NF-κB). In conclusion, our data suggest that LXA4 exerts a neuroprotective effect against neonatal HI brain damage through the IκB/NF-κB pathway. Our findings will help inform future studies regarding the effects of LXA4 on neuroinflammation, blood-brain barrier integrity, and neuronal apoptosis.

Clinical analysis of a case of neonatal exfoliative esophagitis in an 18-day-old neonate.

BACKGROUND: This study aims to provide guidance for clinical work through analysis of the clinical characteristics, endoscopic and pathological manifestations, diagnosis, and treatment of an 18-day-old neonate with exfoliative esophagitis. CASE PRESENTATION: The patient presented with vomiting but the parents did not pay too much attention. The pathological report revealed numerous fibrinous exudative necrotic, and inflammatory cells, as well as a small amount of squamous epithelium. Furthermore, milk allergy factors were considered. Conservative treatments, such as fasting, acid suppression, mucosal protection, parenteral nutrition, and the replacement of anti-allergic milk powder were given. Thereafter, endoscopic examination revealed that the patient returned to normal, and was discharged after 21 days. CONCLUSIONS: Exfoliative esophagitis has multiple causes; and has characteristic clinical and endoscopic manifestations. Endoscopic examination after 18 days presentation and conservative therapy revealed that the esophagus had returned to a normal appearance and the patient was discharged. Following discharge, the parents were advised to feed the patient ALFERE powder. Attention should be given to the timely detection of complications and corresponding treatment.

Glycine Protects against Hypoxic-Ischemic Brain Injury by Regulating Mitochondria-Mediated Autophagy via the AMPK Pathway.

Hypoxic-ischemic encephalopathy (HIE) is detrimental to newborns and is associated with high mortality and poor prognosis. Thus, the primary aim of the present study was to determine whether glycine could (1) attenuate HIE injury in rats and hypoxic stress in PC12 cells and (2) downregulate mitochondria-mediated autophagy dependent on the adenosine monophosphate- (AMP-) activated protein kinase (AMPK) pathway. Experiments conducted using an in vivo HIE animal model and in vitro hypoxic stress to PC12 cells revealed that intense autophagy associated with mitochondrial function occurred during in vivo HIE injury and in vitro hypoxic stress. However, glycine treatment effectively attenuated mitochondria-mediated autophagy. Additionally, after identifying alterations in proteins within the AMPK pathway in rats and PC12 cells following glycine treatment, cyclosporin A (CsA) and 5-aminoimidazole-4-carboxamide-1-b-4-ribofuranoside (AICAR) were administered in these models and indicated that glycine protected against HIE and CoCl2 injury by downregulating mitochondria-mediated autophagy that was dependent on the AMPK pathway. Overall, glycine attenuated hypoxic-ischemic injury in neurons via reductions in mitochondria-mediated autophagy through the AMPK pathway both in vitro and in vivo.

Treatment With Liraglutide Exerts Neuroprotection After Hypoxic-Ischemic Brain Injury in Neonatal Rats via the PI3K/AKT/GSK3ß Pathway.

Neonatal hypoxic-ischemic (HI) brain injury is a detrimental disease, which results in high mortality and long-term neurological deficits. Nevertheless, the treatment options for this disease are limited. Thus, the aim of the present study was to assess the role of liraglutide in neonatal HI brain injury in rats and investigate the associated mechanisms. The results showed that treatment with liraglutide significantly reduced infarct volume and ameliorated cerebral edema, decreased inflammatory response, promoted the recovery of tissue structure, and improved prognosis following HI brain injury. Moreover, treatment with liraglutide inhibited apoptosis and promoted neuronal survival both in the rat model and following oxygen-glucose deprivation (OGD) insult. LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K), partially reversed these therapeutic effects, suggesting that the PI3K/protein kinase B (Akt) pathway was involved. In conclusion, our data revealed that treatment with liraglutide exerts neuroprotection after neonatal HI brain injury via the PI3K/Akt/glycogen synthase kinase-3ß (GSK3ß) pathway and may be a promising therapy for this disease.

Identification and antimicrobial resistance of pathogens in neonatal septicemia in China-A meta-analysis.

OBJECTIVES: The purpose of this study was to analyze the distribution and antimicrobial resistance of common bacterial pathogens causing neonatal septicemia based on a systematic review of published studies in China. METHODS: Articles on neonatal sepsis published in the Chinese literature from 2009 to 2014 were identified according to the inclusion and exclusion criteria. Data were extracted and analyzed using Comprehensive Meta-Analysis software. RESULTS: A total of 71 studies were included, in which a total of 8080 bacterial species were isolated from culture-positive blood samples. The pooled distribution rates of common bacterial pathogens were as follows: Staphylococcus 67.1% (95% confidence interval (CI) 63.3-70.6%), Enterococcus 4.1% (95% CI 3.5-4.8%), Streptococcus 2.3% (95% CI 1.6-3.2%), Escherichia coli 7.4% (95% CI 6.4-8.7%), Klebsiella 6.5% (95% CI 5.2-8.2%), Enterobacterium 2.3% (95% CI 1.9-2.8%), Acinetobacter 1.6% (95% CI 1.3-2.0%), Pseudomonas 1.7% (95% CI 1.3-2.2%). Among the Staphylococcus aureus strains isolated, more than 60% were methicillin-resistant (MRSA). In addition, over 50% of the Gram-negative isolates, including Escherichia and Klebsiella, were resistant to the commonly used third-generation cephalosporins. Most of the Gram-positive and Gram-negative bacteria isolated were sensitive to aminoglycosides, especially amikacin. CONCLUSIONS: It is concluded that Staphylococcus, especially coagulase-negative Staphylococcus, continues to be the principal organism responsible for neonatal septicemia in China; Enterobacteriaceae are common among the Gram-negative isolates. Significant numbers of MRSA and multidrug-resistant Gram-negative bacteria are being isolated as pathogens responsible for neonatal septicemia in China.

Postnatal hyperoxia or DEHP exposure leads to growth restriction and delayed lung development in newborn rats.

BACKGROUND: Di-(2-ethylhexyl) phthalate (DEHP) is commonly used as a plasticizer in many medical devices. We previously showed that maternal DEHP exposure led to restricted growth and delayed lung maturation in newborn rats. As oxygen toxicity continues to be a major risk factor for bronchopulmonary dysplasia, the aim of this study was to examine the effect of hyperoxia, DEHP or DEHP combined with hyperoxia on the growth and lung maturation of newborn rats. METHODS: Newborn rats received DEHP injection, hyperoxia exposure or DEHP injection combined with hyperoxia exposure for one week or two weeks. A control group received an equal volume of vehicle and was maintained in room air. RESULTS: Hyperoxia and hyperoxia + DEHP exposure for one week led to growth failure in newborn rats. Pups in the hyperoxia group showed catch-up growth after being maintained in room air for an additional 7 days but this was not the case with the latter group, which continued to receive DEHP. Hyperoxia and DEHP both delayed lung development, as evidenced by decreased radial alveolar count. Quantitative RT-PCR showed that hyperoxia decreased the transcripts of VEGF, VEGFR-2 and eNOS on days 7 and 14, and DEHP exposure alone also led to decreased expression of VEGF gene in 14-day-old rat pups. CONCLUSION: Postnatal hyperoxia and/or DEHP exposure lead to growth restriction and delayed lung alveolar development. The VEGF gene expression was altered and may be involved as one of the possible molecular mechanisms.

Mortality and Morbidity of Extremely Low Birth Weight Infants in the Mainland of China: A Multi-center Study.

BACKGROUND: With the progress of perinatal medicine and neonatal technology, more and more extremely low birth weight (ELBW) survived all over the world. This study was designed to investigate the short-term outcomes of ELBW infants during their Neonatal Intensive Care Unit (NICU) stay in the mainland of China. METHODS: All infants admitted to 26 NICUs with a birth weight (BW) < l000 g were included between January l, 2011 and December 31, 2011. All the data were collected retrospectively from clinical records by a prospectively designed questionnaire. The data collected from each NICU transmitted to the main institution where the results were aggregated and analyzed. Categorical variables were performed with Pearson Chi-square test. Binary Logistic regression analysis was used to detect risk factors. RESULTS: A total of 258 ELBW infants were admitted to 26 NICUs, of whom the mean gestational age (GA) was 28.1 ± 2.2 weeks, and the mean BW was 868 ± 97 g. The overall survival rate at discharge was 50.0%. Despite aggressive treatment 60 infants (23.3%) died and another 69 infants (26.7%) died after medical care withdrawal. Furthermore, the survival rate was significantly higher in coastal areas than inland areas (53.6% vs. 35.3%, P = 0.019). BW < 750 g and GA < 28 weeks were the largest risk factors, and being small for gestational age was a protective factor related to mortality. Respiratory distress syndrome was the most common complication. The incidence of patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, retinopathy of prematurity was 26.2%, 33.7%, 6.7%, 48.1%, and 41.4%, respectively. Ventilator associated pneumonia was the most common hospital acquired infection during hospitalization. CONCLUSIONS: Our study was the first survey that revealed the present status of ELBW infants in the mainland of China. The mortality and morbidity of ELBW infants remained high as compared to other developed countries.

Whole-exome sequencing identifies USH2A mutations in a pseudo-dominant Usher syndrome family.

Usher syndrome (USH) is an autosomal recessive (AR) multi-sensory degenerative disorder leading to deaf-blindness. USH is clinically subdivided into three subclasses, and 10 genes have been identified thus far. Clinical and genetic heterogeneities in USH make a precise diagnosis difficult. A dominant­like USH family in successive generations was identified, and the present study aimed to determine the genetic predisposition of this family. Whole­exome sequencing was performed in two affected patients and an unaffected relative. Systematic data were analyzed by bioinformatic analysis to remove the candidate mutations via step­wise filtering. Direct Sanger sequencing and co­segregation analysis were performed in the pedigree. One novel and two known mutations in the USH2A gene were identified, and were further confirmed by direct sequencing and co­segregation analysis. The affected mother carried compound mutations in the USH2A gene, while the unaffected father carried a heterozygous mutation. The present study demonstrates that whole­exome sequencing is a robust approach for the molecular diagnosis of disorders with high levels of genetic heterogeneity.

[Clinical analysis of 101 cases of neonatal intestinal perforation].

OBJECTIVE: To analyze the clinical characteristics of neonatal intestinal perforation and to provide a theoretical basis for improving the prognosis of this disease. METHODS: The clinical data of 101 patients with neonatal intestinal perforation who were hospitalized in the Neonatal Intensive Care Unit between January 2000 and June 2014 were retrospectively reviewed. RESULTS: The main causes of neonatal intestinal perforation were neonatal necrotizing enterocolitis (NEC, 41 cases, 40.6%), idiopathic intestinal perforation (17 cases, 16.8%), and congenital megacolon (10 cases, 9.9%). The average birth weight and average gestational age of the idiopathic intestinal perforation group were significantly higher than those of the NEC group (P<0.05). The main pathogen of the NEC group was enterococci, which accounted for 57% (13/23), while in the idiopathic intestinal perforation group Gram-negative bacteria became the major pathogen; the distribution of pathogens were significantly different between the two groups (P<0.05). Multiple logistic regression analysis found that acidosis, multi-site intestinal perforation, and prolonged perforation-operation interval were independent risk factors for death due to neonatal intestinal perforation. CONCLUSIONS: Multiple causes contribute to neonatal intestinal perforation, and NEC is the major one. Neonatal intestinal perforation caused by NEC has different pathogens compared with idiopathic intestinal perforation, and the two diseases may be mutually independent. Early diagnosis and timely operation is the main measure to rescue the lives of patients with neonatal intestinal perforation.

[What is the optimal oxygen saturation for extremely premature infants? A Meta analysis].

OBJECTIVE: To explore an optimal oxygen saturation for extremely preterm infants based on a systemic review of the published studies. METHODS: A Meta analysis of the published studies by the NeOProM Group which compared the outcomes of extremely preterm infants (gestational age <28 weeks) maintained in either a low (85%-89%) or high (91%-95%) oxygen saturation (SpO2) by using the STATA 12.0. The outcomes measured included the mortality and the incidences of retinopathy of prematurity (ROP), necrotizing enterocolitis of newborn (NEC), broncho-pulmonary dysplasia (BPD), intraventricular hemorrhage (IVH) and patent ductus arteriosus (PDA). RESULTS: Three studies were included, in which 2 460 infants were assigned into the low SpO2 group and 2 459 infants in the high SpO2 group. The Meta analysis demonstrated that the risk of mortality before discharge or at the age of 18 months increased in the low SpO2 group compared with the high SpO2 group (RR: 1.19; 95%CI: 1.05-1.35); the risk of ROP decreased in the low SpO2 group (RR: 0.73; 95%CI: 0.53-1.00); the risk of NEC increased in the low SpO2 group (RR: 1.26; 95%CI: 1.06-1.49). There was no significance in the incidences of BPD, IVH and PDA between the two groups. CONCLUSIONS: Maintaining SpO2 at 85%-89% may decrease the incidence of ROP, but increase the mortality rate and the incidence of NEC in extremely premature infants.

Fibroblast growth factors stimulate hair growth through ß-catenin and Shh expression in C57BL/6 mice.

Growth factors are involved in the regulation of hair morphogenesis and cycle hair growth. The present study sought to investigate the hair growth promoting activities of three approved growth factor drugs, fibroblast growth factor 10 (FGF-10), acidic fibroblast growth factor (FGF-1), and basic fibroblast growth factor (FGF-2), and the mechanism of action. We observed that FGFs promoted hair growth by inducing the anagen phase in telogenic C57BL/6 mice. Specifically, the histomorphometric analysis data indicates that topical application of FGFs induced an earlier anagen phase and prolonged the mature anagen phase, in contrast to the control group. Moreover, the immunohistochemical analysis reveals earlier induction of ß-catenin and Sonic hedgehog (Shh) in hair follicles of the FGFs-treated group. These results suggest that FGFs promote hair growth by inducing the anagen phase in resting hair follicles and might be a potential hair growth-promoting agent.