BackgroundGlycosylphosphatidylinositol (GPI) anchoring is a special type of protein posttranslational modification, by which proteins with diverse function are attached to cell membrane through a covalent linkage between the protein and the glycolipid. Phosphatidylinositol glycan anchor biosynthesis class A (PIGA) is a key enzyme in GPI anchor biosynthesis, somatic mutations or genetic variants of which have been associated with paroxysmal nocturnal hemoglobinuria (PNH), or PIGA deficiency, respectively. More than 10 PIGA pathogenic or likely pathogenic variants have been reported in a wide spectrum of clinical syndromes of PIGA deficiency, including multiple congenital anomalies hypotonia‐seizures syndrome 2 (MCAHS2).MethodsWhole‐exome sequencing (WES) was performed on two trios, that is., the proband's family and his affected maternal cousin's family, from a nonconsanguineous Chinese family pedigree with hypotonia‐encephalopathy‐seizures disease history and putative X‐linked recessive inheritance. Sanger sequencing for PIGA variant was performed on affected members as well as unaffected members in the family pedigree to verify its familial segregation.ResultsA novel likely pathogenic variant in PIGA was identified through comparative WES analysis of the two affected families. The single‐nucleotide substitution (NC_000023.9:g.15343279T>C) is located in intron 3 of the PIGA gene and within the splice acceptor consensus sequence (NM_002641.3:c.849‐5A>G). Even though we have not performed RNA studies, in silico tools predict that this intronic variant may alter normal splicing, causing a four base pair insertion which creates a frameshift and a premature stop codon at position 297 (NP_002632.1:p.(Arg283Serfs*15)). Sanger sequencing analysis of the extended family members confirmed the presence of the variant and its X‐linked inheritance.Conclusion WES data analysis along with familial segregation of a rare intronic variant are suggestive of a diagnosis of X‐liked PIGA deficiency with clinical features of MCAHS2.

Objectives We aimed to evaluate the risk factors for moderate-to-severe bronchopulmonary dysplasia (BPD) and focus on discussing its relationship with the duration of initial invasive mechanical ventilation (IMV) in very preterm neonates less than 32 weeks of gestational age (GA). Methods We performed a prospective cohort study involving infants born at 23–31 weeks of GA who were admitted to 47 different neonatal intensive care unit (NICU) hospitals in China from January 2018 to December 2021. Patient data were obtained from the Sina-northern Neonatal Network (SNN) Database. Results We identified 6538 very preterm infants, of whom 49.5% (3236/6538) received initial IMV support, and 12.6% (823/6538) were diagnosed with moderate-to-severe BPD symptoms. The median duration of initial IMV in the moderate-to-severe BPD group was 26 (17–41) days, while in the no or mild BPD group, it was 6 (3–10) days. The incidence rate of moderate-to-severe BPD and the median duration of initial IMV were quite different across different GAs. Multivariable logistic regression analysis showed that the onset of moderate-to-severe BPD was significantly associated with the duration of initial IMV [adjusted odds ratio (AOR): 1.97; 95% confidence interval (CI): 1.10–2.67], late-onset neonatal sepsis (LONS), and patent ductus arteriosus (PDA). Conclusion In this multicenter cohort study, the duration of initial IMV was still relatively long in very premature infants, and the longer duration of initial IMV accounts for the increased risk of moderate-to-severe BPD.

Neonatal sepsis (NS) occurs in neonates within 28 days, especially preterm infants. The dysregulation of miRNAs is widely detected in NS. The study investigated the expression changes and clinical significance of miR-129-5p in NS patients and further explored the regulatory role of miR-129-5p in the LPS-induced inflammatory response in monocytes. A total of 75 neonates with NS and 84 neonates without NS were recruited. qRT-PCR was used for the measurement of miR-129-5p expression. The receiver operating characteristic (ROC) curve was constructed for diagnostic value analysis. ELISA was used to detect the concentration of inflammatory cytokines. Monocytes were isolated from the blood of neonates to investigate the role of miR-129-5p in the LPS-induced inflammatory response in vitro. miR-129-5p was low expressed in the serum of NS cases compared with controls. Serum miR-129-5p had a diagnostic value for NS with a sensitivity of 82.7% and specificity of 79.8%. There was close association for serum miR-129-5p with TNF-α (r = -0.652, p < 0.001) and IL-8 (r = -0.700, p < 0.001) levels in NS patients. Overexpression of miR-129-5p reversed the increasing trend of TNF-α and IL-8 induced by LPS, whereas miR-129-5p downregulation aggravated the increase of TNF-α and IL-8 induced by LPS in monocytes. MiR-129-5p was downregulated in the serum of NS patients, and it might be a promising biomarker for disease diagnosis. Overexpression of miR-129-5p alleviated the inflammatory response of NS.

Human anaplastic lymphoma kinase (ALK) is a potential target for the treatment of pediatric acute lymphoblastic leukemia. However, a number of residue mutations in ALK kinase domain have been observed to cause drug resistance in pediatric acute lymphoblastic leukemia chemotherapy. Here, a chemometrics quantitative structure‐activity relationship predictor was developed using a structure‐based panel of kinase‐inhibitor activity data. The predictor was validated rigorously through internal cross‐validation and external blind test to ensure its statistical reliability, which was then used to computationally construct a systematic activity profile of 13 noncognate kinase inhibitors against both wild‐type ALKwt and cancer‐related variants ALKvt. It is revealed that most noncognate inhibitors exhibit weak potency on ALKwt, but some of them are able to selectively target ALKvt over ALKwt. The chemometrics findings were then evaluated by using a kinase inhibition protocol; results showed that few noncognate inhibitors are 2‐ to 5‐fold higher potent against ALK variant than wild‐type kinase.

The efficacy and safety of ganglioside in the treatment of neonates who suffer from hypoxic-ischemic encephalopathy (HIE) needs to be fully evaluated. We searched the following databases: PubMed, ScienceDirect, LISTA, CNKI, Chinese biomedical literature database and Wanfang digital journals of full-text database to determine the inclusion and exclusion criteria of papers and a total of 12 papers were included after quality evaluation. Then we conducted the meta-analysis with RevMan5.0 software. The results showed that compared with the control group, the abnormal rate declined in the ganglioside-treated group (relative risk (RR)=0.27, 95% confidence interval (CI)= 0.05-1.96). NBNA records of the 7, 10-14d neonates were improved effectively: RR (95% CI) were 2.28 (0.86-3.42) and 2.53 (1.04-2.92) respectively. Neural system sequelae incidence was reduced significantly: RR (95% CI) = 0.35: (0.15-0.79). Ganglioside treatment could effectively reduce the abnormality rate of head size, improve the neurological score, reduce the incidence of neurological sequelae, and significantly prompt clinical recovery for neonates with HIE.

Synopsis A velamentous placenta and umbilical cord torsion may be important contributing factors for premature functional foramen ovale closure. Before major complications develop, the infantile prognosis is usually good.