Correction: High-resolution DNA size enrichment using a magnetic nano-platform and application in non-invasive prenatal testing.

Correction for 'High-resolution DNA size enrichment using a magnetic nano-platform and application in non-invasive prenatal testing' by Bo Zhang et al., Analyst, 2020, 145, 5733-5739, DOI: 10.1039/D0AN00813C.

Clinical treatment outcomes and their changes in extremely preterm twins: a multicenter retrospective study in Guangdong Province, China. / è¶ æœªæˆç†ŸåŒèƒŽå„¿ä¸´åºŠæ•‘æ²»ç»“å±€åŠå˜åŒ–åˆ†æžï¼šä¸€é¡¹å¹¿ä¸œçœå¤šä¸­å¿ƒå›žé¡¾æ€§ç ”ç©¶.

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS: There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.

Synergism of rMV-Hu191 with cisplatin to treat gastric cancer by acid sphingomyelinase-mediated apoptosis requiring integrity of lipid raft microdomains.

BACKGROUND: DDP-based chemotherapy is one of the first-line treatment in GC. However, the therapeutic efficacy of DDP is limited due to side effects. Therefore, it is of great significance to develop novel adjuvants to synergize with DDP. We had demonstrated previously that rMV-Hu191 had antitumor activity in GC. Here we examined the synergism of rMV-Hu191 with DDP in vitro and in vivo. METHODS: Cellular proliferation, the synergistic effect and cell apoptosis were evaluated by CCK-8 assay, ZIP analysis and flow cytometry, respectively. The protein levels and location of ASMase were monitored by western blot and immunofluorescence assay. shRNA and imipramine were used to regulate the expression and activity of ASMase. MßCD was administrated to disrupt lipid rafts. Mice bearing GC xenografts were used to confirm the synergism in vivo. RESULTS: From our data, combinational therapy demonstrated synergistic cytotoxicity both in resistant GC cell lines from a Chinese patient and drug-nonresistant GC cell lines, and increased cell apoptosis, instead of viral replication. Integrity of lipid rafts and ASMase were required for rMV-Hu191- and combination-induced apoptosis. The ASMase was delivered to the lipid raft microdomains at the initial stage of rMV-Hu191 treatment. In vivo GC mice xenografts confirmed the synergism of combinational treatment, together with increased apoptosis and trivial side-effects. CONCLUSIONS: This is the first study to demonstrate that rMV-Hu191 combined with DDP could be used as a potential therapeutic strategy in GC treatment and the ASMase and the integrity of lipid rafts are required for the synergistic effects.

High-resolution DNA size enrichment using a magnetic nano-platform and application in non-invasive prenatal testing.

Precise DNA sizing can boost sequencing efficiency, reduce cost, improve data quality, and even allow sequencing of low-input samples, while current pervasive DNA sizing approaches are incapable of differentiating DNA fragments under 200 bp with high resolution (<20 bp). In non-invasive prenatal testing (NIPT), the size distribution of cell-free fetal DNA in maternal plasma (main peak at 143 bp) is significantly different from that of maternal cell-free DNA (main peak at 166 bp). The current pervasive workflow of NIPT and DNA sizing is unable to take advantage of this 20 bp difference, resulting in sample rejection, test inaccuracy, and restricted clinical utility. Here we report a simple, automatable, high-resolution DNA size enrichment workflow, named MiniEnrich, on a magnetic nano-platform to exploit this 20 bp size difference and to enrich fetal DNA fragments from maternal blood. Two types of magnetic nanoparticles were developed, with one able to filter high-molecular-weight DNA with high resolution and the other able to recover the remaining DNA fragments under the size threshold of interest with >95% yield. Using this method, the average fetal fraction was increased from 13% to 20% after the enrichment, as measured by plasma DNA sequencing. This approach provides a new tool for high-resolution DNA size enrichment under 200 bp, which may improve NIPT accuracy by rescuing rejected non-reportable clinical samples, and enable NIPT earlier in pregnancy. It also has the potential to improve non-invasive screening for fetal monogenic disorders, differentiate tumor-related DNA in liquid biopsy and find more applications in autoimmune disease diagnosis.

[Recognition and discussion of several technical details in neonatal resuscitation training].

In the current revision of neonatal resuscitation training course material and its in-depth learning, referring to the American original textbook on neonatal resuscitation, the authors have some recognition and discussion about its several technical details or translated words. These include the location and time period of postnatal rapid assessment, the expression of respiratory questions, the pressing position in the tracheal intubation, and the expression of respiratory questions in the flow chart of resuscitation, etc. The accurate understanding and interpretation of the above will help grass-roots training to be carried out more accurately and effectively.

WISP1 silencing confers protection against epithelial-mesenchymal transition of renal tubular epithelial cells in rats via inactivation of the wnt/ß-catenin signaling pathway in uremia.

Uremia can affect hepatic metabolism of drugs by regulating the clearance of drugs, but it has not been clarified whether gene silencing could modulate the epithelial-mesenchymal transition (EMT) process in uremia. Hence, we investigated the effect of WISP1 gene silencing on the renal tubular EMT in uremia through the wnt/ß-catenin signaling pathway. Initially, microarray-based gene expression profiling of uremia was used to identify differentially expressed genes. Following the establishment of uremia rat model, serum creatinine, and urea nitrogen of rats were detected. Renal tubular epithelial cells (TECs) were transfected with shRNA-WISP1 lentivirus interference vectors and LiCI (the wnt/ß-catenin signaling pathway activator) to explore the regulatory mechanism of WISP1 in uremia in relation to the wnt/ß-catenin signaling pathway. Then, expression of WISP1, wnt2b, E-cadherin, α-SMA, c-myc, Cyclin D1, MMP-2, and MMP-9 was determined. Furthermore, TEC migration and invasion were evaluated. Results suggested that WISP1 and the wnt/ß-catenin signaling pathway were associated with uremia. Uremic rats exhibited increased serum creatinine and urea nitrogen levels, upregulated WISPl, and activated wnt/ß-catenin signaling pathway. Subsequently, WISP1 silencing decreased wnt2b, c-myc, Cyclin D1, α-SMA, MMP-2, and MMP-9 expression but increased E-cadherin expression, whereas LiCI treatment exhibited the opposite trends. In addition, WISP1 silencing suppressed TEC migration and invasion, whereas LiCI treatment promoted TEC migration and invasion. The findings indicate that WISP1 gene silencing suppresses the activation of the wnt/ß-catenin signaling pathway, thus reducing EMT of renal TECs in uremic rats.

[Clinical efficacy of nasal high-frequency ventilation in treatment of neonatal respiratory distress syndrome: a Meta analysis].

OBJECTIVE: To systematically evaluate the clinical efficacy of nasal high-frequency ventilation (nHFV) in the treatment of neonatal respiratory distress syndrome (NRDS). METHODS: A literature search was performed in PubMed, Cochrane Library, EMBase (Ovid), Chinese Biomedical Literature Database, Chinese Journal Full-text Database, Wanfang Data, and Weipu Data to collect the randomized controlled trials (RCTs) that compared the clinical efficacy of nHFV and nasal continuous positive airway pressure (nCPAP) in the treatment of NRDS. A Meta analysis was performed on the included RCTs using Rev Man 5.3 software after data extraction and quality evaluation by Cochrane 5.1.0. RESULTS: A total of 4 RCTs involving 218 patients were included. The Meta analysis showed that compared with the nCPAP group, the nHFV group had a significantly better treatment outcome (RR=1.73, 95%CI: 1.39-2.15, P<0.00001). There were no significant differences in the incidence rates of intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, necrotizing enterocolitis, pneumothorax and retinopathy of prematurity. CONCLUSIONS: Compared with nCPAP, nHFV has better clinical efficacy in the treatment of NRDS, without increasing the risk of related complications.

[Relationship between serum erythropoietin levels and brain injury in preterm infants].

OBJECTIVE: To study the relationship between the levels of erythropoietin (EPO) in serum and brain injury in preterm infants. METHODS: Three hundred and four preterm infants (gestational age: 28-34 weeks) born between October 2014 and September 2015 were enrolled in this study. Brain injury was diagnosed using cerebral ultrasound and MRI. The levels of EPO, S100 protein, neuron-specific enolase (NSE) and myelin basic protein (MBP) in serum were detected using ELISA. To compare the incidence of brain injury in different serum EPO levels in preterm infants, and the relationship between brain injury and serum EPO levels was analyzed. RESULTS: The incidence rate of brain injury in preterm infants was 41.1% (125/304). The incidence rate of brain injury in the low EPO level group was significantly higher than that in the middle-high EPO level groups (P<0.01). The serum levels of S100 protein, NSE, and MBP in the brain injury groups were significantly higher than in the control group (P<0.01). The serum EPO levels were negatively correlated with serum S100 protein concentration and NSE levels (P<0.05). According to the multiple logistic regression analysis, low gestational age, low birth weight, asphyxia, prolonged mechanical ventilation, anemia and low serum EPO levels were the risk factor for brain injury in preterm infants. CONCLUSIONS: There is a higher incidence rate of brain injury in preterm infants with lower serum EPO levels. The serum EPO levels may be correlated with brain injury in preterm infants.

[Analysis of CYP21A2 gene mutation in one case of congenital adrenal hyperplasia].

CYP21A2 gene mutations in a child with congenital adrenal hyperplasia (CAH), and the child's parents, were detected in the study. The clinical features, treatment monitoring and molecular genetic mechanism of CAH are reviewed. In the study, DNA was extracted from peripheral blood samples using the QIAGEN Blood DNA Mini Kit; a highly specific PCR primer for CYP21A2 gene was designed according to the sequence difference between CYP2lA2 gene and its pseudogene; the whole CYP2lA2 gene was amplified with PrimeSTAR DNA polymerase (Takara), and the amplification product was directly sequenced to detect and analyze CYP2lA2 gene mutation. The child was clinically diagnosed with CAH (21-hydroxylase deficiency, 21-OHD) at the age of 36 days, and the case was confirmed by genetic diagnosis at the age of 1.5 years. The proband had a homozygous mutation at c.293-13C in the second intron of CYP21 gene, while the parents had heterozygous mutations. Early diagnosis and standard treatment of CAH (21-OHD) should be performed to prevent salt-wasting crisis and reduce mortality; bone aging should be avoided to increase final adult height (FAH), and reproductive dysfunction due to oligospermia in adulthood should be avoided. These factors are helpful for improving prognosis and increasing FAH. Investigating the molecular genetic mechanism of CAH can improve recognition and optimize diagnosis of this disease. In addition, carrier diagnosis and genetic counseling for the proband family are of great significance.

A multicenter prospective study of next-generation sequencing-based newborn screening for monogenic genetic diseases in China.

BACKGROUND: Newborn screening (NBS) is an important and successful public health program that helps improve the long-term clinical outcomes of newborns by providing early diagnosis and treatment of certain inborn diseases. The development of next-generation sequencing (NGS) technology provides new opportunities to expand current newborn screening methodologies. METHODS: We designed a a newborn genetic screening (NBGS) panel targeting 135 genes associated with 75 inborn disorders by multiplex PCR combined with NGS. With this panel, a large-scale, multicenter, prospective multidisease analysis was conducted on dried blood spot (DBS) profiles from 21,442 neonates nationwide. RESULTS: We presented the positive detection rate and carrier frequency of diseases and related variants in different regions; and 168 (0.78%) positive cases were detected. Glucose-6-Phosphate Dehydrogenase deficiency (G6PDD) and phenylketonuria (PKU) had higher prevalence rates, which were significantly different in different regions. The positive detection of G6PD variants was quite common in south China, whereas PAH variants were most commonly identified in north China. In addition, NBGS identified 3 cases with DUOX2 variants and one with SLC25A13 variants, which were normal in conventional NBS, but were confirmed later as abnormal in repeated biochemical testing after recall. Eighty percent of high-frequency gene carriers and 60% of high-frequency variant carriers had obvious regional differences. On the premise that there was no significant difference in birth weight and gestational age, the biochemical indicators of SLC22A5 c.1400C > G and ACADSB c.1165A > G carriers were significantly different from those of non-carriers. CONCLUSIONS: We demonstrated that NBGS is an effective strategy to identify neonates affected with treatable diseases as a supplement to current NBS methods. Our data also showed that the prevalence of diseases has significant regional characteristics, which provides a theoretical basis for screening diseases in different regions.

[Risk factors and pathogen distribution in premature infants with nosocomial sepsis].

OBJECTIVE: To investigate the main risk factors and pathogen distribution of nosocomial sepsis among premature infants. METHODS: The clinical data of 3418 hospitalized premature infants from January 2003 to December 2010 were retrospectively analyzed for the risk factors and pathogen distribution of nosocomial sepsis. RESULTS: The incidence of neonatal nosocomial sepsis was 3.10% (106/3418), and the median age at diagnosis of neonatal nosocomial sepsis was 19 (4-48) days. The major pathogens of the infections among these premature infants included gram-positive bacteria (45.2%), especially coagulase-negative Staphylococcus (24.3%), and gram-negative bacteria (41.7%), especially Klebsiella pneumoniae (25.2%), as well as fungus (13.0%). Logistic regression analysis showed that the main risk factors included low birth weight, retention of central venous catheters, and long duration of parenteral nutrition (OR: 3.765, 3.051, and 2.998, respectively; P<0.05). CONCLUSIONS: Low birth weight, retention of central venous catheters, and long duration of parenteral nutrition are the main risk factors for neonatal nosocomial sepsis, whereas the leading pathogen is Klebsiella pneumoniae.

Short term outcomes of extremely low birth weight infants from a multicenter cohort study in Guangdong of China.

With the increase in extremely low birth weight (ELBW) infants, their outcome attracted worldwide attention. However, in China, the related studies are rare. The hospitalized records of ELBW infants discharged from twenty-six neonatal intensive care units in Guangdong Province of China during 2008-2017 were analyzed. A total of 2575 ELBW infants were enrolled and the overall survival rate was 55.11%. From 2008 to 2017, the number of ELBW infants increased rapidly from 91 to 466, and the survival rate improved steadily from 41.76% to 62.02%. Increased survival is closely related to birth weight (BW), regional economic development, and specialized hospital. The incidence of complications was neonatal respiratory distress syndrome (85.2%), oxygen dependency at 28 days (63.7%), retinopathy of prematurity (39.3%), intraventricular hemorrhage (29.4%), necrotizing enterocolitis (12.0%), and periventricular leukomalacia (8.0%). Among the 1156 nonsurvivors, 90.0% of infants died during the neonatal period (≤ 28 days). A total of 768 ELBW infants died after treatment withdrawal, for reasons of economic and/or poor outcome. The number of ELBW infants is increasing in Guangdong Province of China, and the overall survival rate is improving steadily.

Using random forest to detect multiple inherited metabolic diseases simultaneously based on GC-MS urinary metabolomics.

Inborn errors of metabolism, also known as inherited metabolic diseases (IMDs), are related to genetic mutations and cause corresponding biochemical metabolic disorder of newborns and even sudden infant death. Timely detection and diagnosis of IMDs are of great significance for improving survival of newborns. Here we propose a strategy for simultaneously detecting six types of IMDs via combining GC-MS technique with the random forest algorithm (RF). Clinical urine samples from IMD and healthy patients are analyzed using GC-MS for acquiring metabolomics data. Then, the RF model is established as a multi-classification tool for the GC-MS data. Compared with the models built by artificial neural network and support vector machine, the results demonstrated the RF model has superior performance of high specificity, sensitivity, precision, accuracy, and matthews correlation coefficients on identifying all six types of IMDs and normal samples. The proposed strategy can afford a useful method for reliable and effective identification of multiple IMDs in clinical diagnosis.

A recombinant Chinese measles virus vaccine strain rMV-Hu191 inhibits human colorectal cancer growth through inducing autophagy and apoptosis regulating by PI3K/AKT pathway.

The potential therapeutic effects of oncolytic measles virotherapy have been verified against plenty of malignancies. However, the oncolytic effects and underlying mechanisms of the recombinant Chinese measles virus vaccine strain Hu191 (rMV-Hu191) against human colorectal cancer (CRC) remain elusive. In this study, the antitumor effects of rMV-Hu191 were evaluated in CRC both in vitro and in vivo. From our data, rMV-Hu191 induced remarkably caspase-dependent apoptosis and complete autophagy in vitro. In mice bearing CRC xenografts, tumor volume was remarkably suppressed and median survival was prolonged significantly with intratumoral treatment of rMV-Hu191. To gain further insight into the relationship of rMV-Hu191-induced apoptosis and autophagy, we utilized Rapa and shATG7 to regulate autophagy. Our data suggested that autophagy was served as a protective role in rMV-Hu191-induced apoptosis in CRC. PI3K/AKT signaling pathway as one of the common upstream pathways of apoptosis and autophagy was activated in CRC after treatment with rMV-Hu191. And inhibition of PI3K/AKT pathway using LY294002 was accompanied by enhanced apoptosis and decreased autophagy which suggested that PI3K/AKT pathway promoted rMV-Hu191-induced autophagy and inhibited rMV-Hu191-induced apoptosis. This is the first study to demonstrate that rMV-Hu191 could be used as a potentially effective therapeutic agent in CRC treatment. As part of the underlying cellular mechanisms, apoptosis and autophagy were involved in the oncolytic effects generated by rMV-Hu191. And the cross-talk between these two processes and the PI3K/AKT signaling pathway was well identified.

Comparison of acute pneumonia caused by SARS-COV-2 and other respiratory viruses in children: a retrospective multi-center cohort study during COVID-19 outbreak.

BACKGROUND: Until January 18, 2021, coronavirus disease-2019 (COVID-19) has infected more than 93 million individuals and has caused a certain degree of panic. Viral pneumonia caused by common viruses such as respiratory syncytial virus, rhinovirus, human metapneumovirus, human bocavirus, and parainfluenza viruses have been more common in children. However, the incidence of COVID-19 in children was significantly lower than that in adults. The purpose of this study was to describe the clinical manifestations, treatment and outcomes of COVID-19 in children compared with those of other sources of viral pneumonia diagnosed during the COVID-19 outbreak. METHODS: Children with COVID-19 and viral pneumonia admitted to 20 hospitals were enrolled in this retrospective multi-center cohort study. A total of 64 children with COVID-19 were defined as the COVID-19 cohort, of which 40 children who developed pneumonia were defined as the COVID-19 pneumonia cohort. Another 284 children with pneumonia caused by other viruses were defined as the viral pneumonia cohort. The epidemiologic, clinical, and laboratory findings were compared by Kolmogorov-Smirnov test, t-test, Mann-Whitney U test and Contingency table method. Drug usage, immunotherapy, blood transfusion, and need for oxygen support were collected as the treatment indexes. Mortality, intensive care needs and symptomatic duration were collected as the outcome indicators. RESULTS: Compared with the viral pneumonia cohort, children in the COVID-19 cohort were mostly exposed to family members confirmed to have COVID-19 (53/64 vs. 23/284), were of older median age (6.3 vs. 3.2 years), and had a higher proportion of ground-glass opacity (GGO) on computed tomography (18/40 vs. 0/38, P < 0.001). Children in the COVID-19 pneumonia cohort had a lower proportion of severe cases (1/40 vs. 38/284, P = 0.048), and lower cases with high fever (3/40 vs. 167/284, P < 0.001), requiring intensive care (1/40 vs. 32/284, P < 0.047) and with shorter symptomatic duration (median 5 vs. 8 d, P < 0.001). The proportion of cases with evaluated inflammatory indicators, biochemical indicators related to organ or tissue damage, D-dimer and secondary bacterial infection were lower in the COVID-19 pneumonia cohort than those in the viral pneumonia cohort (P < 0.05). No statistical differences were found in the duration of positive PCR results from pharyngeal swabs in 25 children with COVID-19 who received antiviral drugs (lopinavir-ritonavir, ribavirin, and arbidol) as compared with duration in 39 children without antiviral therapy [median 10 vs. 9 d, P = 0.885]. CONCLUSION: The symptoms and severity of COVID-19 pneumonia in children were no more severe than those in children with other viral pneumonia. Lopinavir-ritonavir, ribavirin and arbidol do not shorten the duration of positive PCR results from pharyngeal swabs in children with COVID-19. During the COVID-19 outbreak, attention also must be given to children with infection by other pathogens infection.

[Lung fibrosis induced by mechanical ventilation with different tidal volume in neonatal rats].

OBJECTIVE: To study the changes of collagen synthesis following mechanical ventilation with different tidal volume and the possible mechanism. METHODS: Twenty-four neonatal Sprague-Dawley rats were randomized to hyperventilation (tidal volume 25 mL/kg), conventional ventilation (tidal volume 10 mL/kg) and no mechanical ventilation (control group) (n=8 each group). They were sacrificed 5 hrs after ventilation. Left lung samples were used for histopathologic examinations and the detection of connective tissue growth factor (CTGF) expression by immunohistochemistry. Right lung samples were used for the detection of expression of procollagenIII mRNA(PcolIII mRNA), cysteinyl leukotriene mRNA(CysLT1 mRNA)and CTGF mRNA by PCR. RESULTS: The severity of lung injury and fibrosis increased significantly with the increasing tidal volume compared with the control group. Lung CTGF mRNA expression in the hyperventilation group was significantly higher than that in the control group (P<0.05). Lung PcolIII mRNA and CysLT1 mRNA levels increased with the increasing tidal volume when compared with the control group. The differences in PcolIII mRNA and CysLT1 mRNA levels between groups were significant (P<0.05). There was a positive correlation between lung PcolIII mRNA expression and the severity of lung injury (r=0.78,P<0.01). CTGF and CysLT levels were positively correlated with PcolIII expression (r = 0.59,0.86,P<0.01). CONCLUSIONS: Mechanical ventilation using different tidal volume leads to different severities of lung injury, followed by the occurrence of lung fibrosis. The degree of lung fibrosis is consistent with the severity of lung injury. CysLT and CTGF may be involved in the development of lung fibrosis.

[Effect of erythropoietin on apoptosis following hyperoxic lung injury in neonatal rats].

OBJECTIVE: To study the effect of recombinant human erythropoietin (rhEPO) on apoptosis following hyperoxic lung injury in neonatal rats. METHODS: Ninety-six neonatal Sprague-Dawley rats were randomly divided into four groups: air-exposed control, air-exposed rhEPO-treated, hyperoxia-exposed placebo (95% oxygen), and hyperoxia-exposed rhEPO-treated. rhEPO (800 U/kg) was administered 2, 4, and 6 days after air or hyperoxia exposure. The rats were sacrificed 3, 7 and 14 days after air or hyperoxia exposure for the assessment of lung histological changes by hematoxylin and eosin staining (n=8 each time point). p-JNK levels were measured by Western blot. Lung cell apoptosis was evaluated by TUNEL assay. RESULTS: Compared with the air-exposed control group, inflammatory cell infiltration was found at 3 days and increased obviously at 7 days, and widening of the alveolar septa was observed, the number of alveoli decreased and normal alveolarization disappeared at 14 days after hyperoxia exposure in the hyperoxia-exposed placebo group. rhEPO treatment alleviated significantly the hyeroxia-induced alterations in lung pathology. P-JNK protein levels and the number of apoptosis cells decreased significantly in the hyperoxia-exposed rhEPO-treated compared with those in the hyperoxia-exposed placebo group. CONCLUSIONS: rhEPO may reduce apoptosis and thus provide a protective effect against hyperoxic lung injury in neonatal rats. JNK signal pathway may be involved in the protective mechanism.

Coupling bootstrap with synergy self-organizing map-based orthogonal partial least squares discriminant analysis: Stable metabolic biomarker selection for inherited metabolic diseases.

Biomarker selection has played an increasingly important part in modern medicine with advances of omics techniques. Kohonen self-organizing map is a well-established variable reduction algorithm in identifying significant biomarkers based on variable clustering. However, high dimensionality but small sample size of omics data makes self-organizing map-based model problematic in terms of selection stability and reproducibility. A novel feature screening system is presented in this study by coupling bootstrap with synergy self-organizing map-based orthogonal partial least squares discriminant analysis for stable and biologically meaningful metabolic biomarker selection. In the proposed feature screening system, particle swarm optimization algorithm is utilized to configure synergy self-organizing map-based orthogonal partial least squares discriminant analysis to perform the combination of clusters in a heuristic learning manner, enabling flexible selection of more informative features cost-effectively. Based on the paradigm of ensemble feature selection, bootstrap is adopted to explore significant variables consistently identified across multiple feature selectors rather than a single one. The feasibility of the novel feature screening system is evaluated by two most common inherited metabolic diseases, methylmalonic academia and propionic academia, using urinary metabolomics data. With the desirable classification performance, the proposed feature screening system outperforms simpler techniques in the identification of more features closely correlated with the metabolic mechanisms and the stability of selected candidate biomarkers against sample variations. Besides, the novel feature screening system greatly degrades the sensitivity of identified candidate biomarkers to the network size of self-organizing map, benefiting the identification of a suitable and stable final candidate biomarker list.

[Multicenter follow-up report of 147 premature infants with brain injuries from 6 hospitals in China].

OBJECTIVE: Sponsored by the Subspecialty Group of Neonatology of Pediatric Society, China Medical Association, more than 10 large-scale hospitals participated in the near two-year multicenter investigation for Brain Injuries in Premature Infants in China. The present study presents the follow-up results of 147 premature infants with brain injuries from 6 Third Class A Level hospitals. METHODS: All premature infants with intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL) diagnosed in the early neonatal period in the 6 hospitals were followed-up between January 2005 and August 2006. Based on the synthetic results of physical development, examination of nervous system, intelligence tests and cranial ultrasound, the premature infants with brain injuries were classified as normal development, marginal development and retarded development. RESULTS: One hundred and forty-seven premature infants with brain injuries from the 6 hospitals consisted of 141 cases of IVH and 36 cases of PVL (30 cases having IVH and PVL). Based on the synthetic follow-up results, 51.4% of premature infants with brain injuries were generally assessed as normal development, 38.4% as marginal development and 10.7% as retarded development. Among them, delayed growth in head circumference, height and weight was 13.4%; the occurrence frequency of cerebral paralysis (CP) was 7.1% in PVL grade I, 28.6% in PVL grade II and 100% in PVL grade III; 12.7% showed retarded development of intelligence; and 30% presented post-injurious changes on cranial sonography. CONCLUSIONS: The data of the multicenter follow-up can basically reflect the short-term prognosis of premature infants with brain injuries in major big cities of China. About 10% of them have retarded physical, motor-and mental developments. The long-term regular follow-up study is expected for more premature infants with brain injuries, and behavioral sequelae of brain injuries which may occur in peri-school age and adolescence should be paid particularly close attention.

Early diagnosis of necrotizing enterocolitis by plasma RELMß and thrombocytopenia in preterm infants: A pilot study.

BACKGROUND: As the inflammatory regulators, Resistin-like molecule ß (RELMß) and Resistin might be potential biomarkers of necrotizing enterocolitis (NEC), while thrombocytopenia is often related to the severity of NEC, clinical observation suggests that thrombocytopenia might be an early biomarker of NEC. The aim of this study was to evaluate whether RELMß, Resistin and thrombocytopenia could be biomarkers for early diagnosis of NEC in preterm infants. METHODS: From January 2016 to March 2018, twenty-nine NEC preterm infants who were diagnosed with NEC (Bell's stage ≥Ⅱ) by two independent neonatologists and twenty-nine non NEC preterm infants at neonatal intensive care unit in our hospital were enrolled in this case-control study. Preterm infants with a history of serious infections (sepsis, pneumonia), asphyxia, and congenital malformations were excluded from the study. The plasma RELMß and Resistin were evaluated by enzyme linked immunosorbent assay (ELISA) and serum platelet levels were measured directly by ordinary light microscope at the diagnosis of NEC (Bell's stage ≥Ⅱ). RESULTS: Plasma RELMß levels in NEC group were significantly higher than control group (P < 0.05). The optimal cut-off value of RELMß determined by receiver operating characteristic curve (ROC) was 378.3 ng/L. The overall estimates for sensitivity and specificity of high RELMß concentrations in the detection of neonatal NEC were 71.4% and 91.7%, respectively. No significant difference was found in plasma Resistin levels between two groups (P > 0.05). If platelet level was less than 157 × 109/L, the sensitivity and specificity were 69.34% and 82.87%, respectively. Interestingly, the combination of RELMß and thrombocytopenia increased sensitivity and specificity to 82.89% and 93.21%, respectively. CONCLUSION: The combination of RELMß and thrombocytopenia was a reliable biomarker for the early diagnosis of NEC in this study with 82.89% sensitivity and 93.21% specificity, respectively.