Beneficial changes in gut microbiota after phototherapy for neonatal hyperbilirubinemia.

Phototherapy is the most commonly used treatment for neonatal hyperbilirubinemia (NH). Gut microbiota is involved in bilirubin metabolism; however, it is uncertain whether this is affected by phototherapy. The present study included 43 newborns with hyperbilirubinemia and collected fecal samples for high-throughput sequencing before and after phototherapy. Selection α diversity analysis was used to determine the differences in diversity and abundance between the two groups, whereas similarity was determined using ß diversity analysis. Linear discriminant analysis effect size analysis was used to screen for markedly different bacteria. The structure of the gut microbiota in newborns with hyperbilirubinemia changed after phototherapy, with a significant decrease in abundance and diversity. The changes in the key bacterial species were characterized by an increase in the abundance of Streptococcus salivarius and a decrease in the abundance of Escherichia, Klebsiella pneumoniae, Rothia mucilaginosa and Streptococcus oralis. These changes mainly manifested as an increase in beneficial bacteria and a decrease in opportunistic bacteria, which may not be related to the side effects of phototherapy. These results can provide theoretical assistance for microbiological research on the later stages of NH.

[A case of Neonatal generalized atrophic benign epidermolysis bullosa due to variants of COL17A1 gene].

OBJECTIVE: To diagnose and explore the genetic etiology of a neonate with Hereditary epidermolysis bullosa. METHODS: A neonate who was admitted to Suqian Hospital Affiliated to Xuzhou Medical University on July 10, 2021 was selected as the study subject. Peripheral blood samples were collected from the child and his parents for the extraction of genomic DNA. And target gene capture and next-generation sequencing were carried out. Candidate variants were verified by Sanger sequencing and pathogenicity analysis. RESULTS: The child was found to harbor compound heterozygous variants of the COL17A1 gene, namely c.997C>T (p.Q333X) and c.3481dupT (p.Y1161fs*2), which were respectively inherited from his father and mother. Both variants were predicted to be pathogenic. CONCLUSION: The child was diagnosed with Generalized atrophic benign epidermolysis bullosa due to the compound heterozygous variants of the COL17A1 gene.

Thrombopoietin receptor agonists use and risk of thrombotic events in patients with immune thrombocytopenic purpura: A systematic review and meta­analysis of randomized controlled trials.

Thrombopoietin receptor agonists (TPO-RAs) have a role in second-line immune thrombocytopenic purpura (ITP) treatment, binding to and activating thrombopoietin receptors on megakaryocyte membranes in the bone marrow. This promotes megakaryocyte maturation and increases platelet production. Despite a 2-6% incidence of thrombotic events during TPO-RA treatment, it remains uncertain whether TPO-RAs elevate thrombosis rates. A comprehensive search of electronic databases was conducted using the relevant search criteria. To assess the risk of bias, the included studies were assessed using the revised Cochrane Risk of Bias Assessment Tool 2.0, and a meta-analysis was performed using RevMan 5.4.1. A total of 1,698 patients with ITP were included from randomized controlled trials (RCTs). There were 26 thromboembolic events in the TPO-RAs group and 4 in the control group. However, there was no significant difference in the incidence of thrombotic events between the two groups [odds ratio (OR)=1.76, 95% confidence interval (CI): 0.78-4.00, P=0.18], even if the duration of treatment was >12 weeks (OR=2.46, 95% CI: 0.81-7.43, P=0.11). Subgroup analysis showed that none of the four drugs significantly increased the incidence of thrombotic events (romiplostim: OR=0.92, 95% CI: 0.14-6.13, P=0.93; eltrombopag: OR=2.32, 95% CI: 0.64-8.47, P=0.20; avatrombopag: OR=4.15, 95% CI: 0.20-85.23, P=0.36; and hetrombopag: OR=0.76, 95% CI: 0.03-18.76, P=0.87). There was also no significant difference in the results of the double-blinded placebo-controlled RCTs (OR=1.21, 95% CI: 0.41-3.58, P=0.73). Compared to patients with ITP who did not receive TPO-RA treatment, those receiving TPO-RA treatment did not exhibit a significantly increased risk of thrombotic events.

Hyponatremia as a Marker for Predicting Surgical Intervention in Necrotizing Enterocolitis: A Retrospective Cohort Study.

INTRODUCTION: To investigate the predictive value of plasma sodium at the onset of necrotizing enterocolitis (NEC) diagnosis in distinguishing surgical NEC from medical NEC. METHODS: A retrospective review of all NEC neonates treated at our hospital between 2008 and 2022. Patients were divided into two groups based on treatment methods: surgical intervention and medical treatment. Patient demographics, laboratory parameters, and outcomes were all documented. The values of laboratory parameters were collected at the onset of NEC and after treatment. To identify potential predictors of surgical NEC, multivariate logistic regression analyses were used. The receiver operating characteristic curve was applied to determine predictive factors. RESULTS: Surgical treatment was performed in 111 infants (44.6%), and medical treatment in 138 cases (55.4%). Of 249 infants with NEC, 22 patients exhibited Bell stage I, 91 infants had Bell stage II, and 136 patients displayed Bell stage III. We discovered that white blood cell (WBC), C-reactive protein (CRP), fibrinogen, and sodium were independent predictors of NEC receiving surgery based on the results of the multivariate logistic regression analysis. Hyponatremia was found in 122 of the 249 patients (49%). At the onset of NEC diagnosis, hyponatremia was found in 83.8% of surgical intervention group and in 21.0% of medical treatment group (P < 0.001). Sensitivity, specificity, positive predictive value, and negative predictive value for WBC, CRP, fibrinogen, and sodium were calculated. The cutoff values were determined using receiver operating characteristic analysis. The area under the curve of hyponatremia for surgical intervention was 0.875, with 84% sensitivity, 80% specificity, 77% positive predictive value, and 86% negative predictive value, which had a greater specificity (0.80) for predicting surgical intervention than WBC (0.67), CRP (0.50), and fibrinogen (0.70). CONCLUSIONS: When a surgical evaluation is necessary, hyponatremia can effectively distinguish surgical NEC from medical NEC. It could be used as a predictive marker to guide parental counseling for surgical intervention and rapid transfer of patients to tertiary centers when they have a surgical condition.

Case report of self-improving collodion ichthyosis in the newborn.

Self-improving collodion ichthyosis (SICI) is a relatively rare subtype of autosomal recessive congenital ichthyosis (ARCI) that is often characterized by a collodion baby (CB) phenotype at birth. A newborn girl, just 1 hour old, presented with taut, shiny, thick yellow crusts, like parchment, and scales on her trunk and upper limbs. The tightening effect had caused both upper eyelids to appear everted, and her lips and auricles were deformed. Based on whole-exome sequencing and examination of the clinical phenotype, the patient was diagnosed with ARCI. After admission, the exposed mucosa was covered with a sterile Vaseline gauze dressing, and she was placed in an incubator set to a temperature of 32°C with a humidity level of 75%. One week later, the parchment-like scales had begun to flake off, and at the age of 3 weeks, all bodily skin appeared normal. SICI was diagnosed. After discharge, the patient was followed up to 3 months of age, at which time her growth and development were comparable to those of her peers. Clinicians should consider SICI as a possible diagnosis when analyzing the prognosis of patients with CB. Reducing water loss and maintaining the electrolyte balance are particularly important for SICI treatment.

Safety of non­peptide thrombopoietin receptor agonists in patients with immune thrombocytopenia: A systematic review and meta­analysis of short­term double­blind randomized clinical trials.

The aim of the present study was to analyze the safety of non-peptide thrombopoietin receptor agonists (TPO-RAs) for immune thrombocytopenia (ITP) treatment. All studies reporting adverse events (AEs) in relation to ITP treatment with eltrombopag, avatrombopag, and hetrombopag were retrieved from PubMed, Web of Science, and Embase databases. RevMan 5.4.1 was used for meta-analysis, heterogeneity and bias analyses. A total of 1,078 patients from seven eligible studies were enrolled. In the enrolled clinical trials, the double-blind period was between 6 weeks and 6 months. The results revealed that the chances of any AEs [relative risk (RR)=1.16; 95% confidence interval (CI), 0.90-1.51; I2=78%; P=0.26], grade 3/4 AEs (RR=1.07; 95% CI, 0.63-1.80; I2=0%; P=0.81), elevated transaminase levels (RR=1.09; 95% CI, 0.68-1.74; I2=0%; P=0.72), thrombosis (RR=1.92; 95% CI, 0.55-6.66; I2=0%; P=0.31) and cataracts (RR=0.83; 95% CI, 0.38-1.83; I2=0%; P=0.65) were not significantly higher in patients with ITP that received non-peptide TPO-RAs compared with patients with ITP treated with a placebo. The present study indicated that non-peptide TPO-RAs were relatively safe for patients with ITP, at least within 6 months of administration.

Screening of Efficient Adjuvants for the RBD-Based Subunit Vaccine of SARS-CoV-2.

The variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more transmissible, with a reduced sensitivity to vaccines targeting the original virus strain. Therefore, developing an effective vaccine against both the original SARS-CoV-2 strain and its variants is an urgent need. It is known that the receptor-binding domain (RBD) in the S protein of SARS-CoV-2 is an important vaccine target, but subunit vaccines usually have lower immunogenicity and efficacy. Thus, selecting appropriate adjuvants to enhance the immunogenicity of protein-based subunit vaccine antigens is necessary. Here, an RBD-Fc subunit vaccine of SARS-CoV-2 has been generated, followed by vaccination in B6 mice, and four adjuvant regimens were investigated, including aluminum salts (Alum) + 3-O-desacyl-4'-monophosphoryl lipid A (MPL), AddaVax, QS21 + MPL, and Imiquimod. The adjuvant potency was evaluated by comparing the elicited polyclonal antibodies titers with measuring binding to RBD and S protein in ELISA and Western blot analysis, and also the cross-neutralizing antibodies titers using a pseudovirus infection assay of hACE2-expressing 293T cells, with pseudoviruses expressing the S protein of the SARS-CoV-2 original strain and Delta strain. The presence of QS21 + MPL adjuvant induced stronger polyclonal antibody response and neutralization potency blocking the original strain and Delta strain, as compared with the non-adjuvant RBD-Fc group and other adjuvant groups. Meanwhile, Imiquimod even had a negative effect in inducing specific antibodies and cross-neutralizing antibody production as an adjuvant.

Open versus closed reduction internal fixation for lateral condyle humeral fractures in children: a systematic review and meta-analysis.

OBJECTIVE: The objective of this meta-analysis was to illustrate the clinical outcomes and safety of two different management options for Song stage 2-4 lateral condyle humeral fractures in children. METHOD: In January 2023, a systematic computer-based search was conducted. Data were retrieved for patients with two different management options for lateral condyle humeral fractures in children. The primary endpoints were clinical outcomes based on infection, avascular necrosis, and nonunion. After testing for publication bias and heterogeneity between studies, the data was aggregated for stochastic effect models when necessary. RESULTS: Eight clinical studies with 742 patients were eventually included in the meta-analysis. There was no significant difference between the closed reduction and percutaneous pinning, and open reduction and internal fixation in terms of the clinical outcomes based on infection, avascular necrosis, and nonunion (P > 0.05). CONCLUSIONS: Closed reduction and percutaneous pinning, as well as open reduction and internal fixation of lateral condyle humeral fractures in children, resulted in similar structural stability and functional outcomes. More high-quality randomized controlled trials are needed to determine this conclusion.

Activation of M3-AChR and IP3/Ca2+/PKC signaling pathways by pilocarpine increases glycine-induced currents in ventral horn neurons of the spinal cord.

Our study aimed to determine the effects of pilocarpine and the mechanisms involving muscarinic acetylcholine receptors (mAChRs) on glycine receptors (GlyRs) in neurons of the spinal cord ventral horn. An enzymatic digestion combined with acute mechanical separation was applied to isolate neurons from the spinal cord ventral horn. Patch-clamp recording was then used to investigate the outcomes of pilocarpine. Our results indicate that pilocarpine increased the glycine currents in a concentration-dependent manner, which was blocked by the M3-AChR selective antagonists 4-DAMP and J104129. Pilocarpine also enhanced the glycine currents in nominally Ca2+-free extracellular solution. Conversely, the enhancement of glycine currents by pilocarpine disappeared when intracellular Ca2+ was chelated by BAPTA. Heparin and Xe-C, which are IP3 receptor antagonists, also totally abolished the pilocarpine effect. Furthermore, Bis-IV, a PKC inhibitor, eliminated the pilocarpine effect. Additionally, PMA, a PKC activator, mimicked the pilocarpine effect. These results indicate that pilocarpine may increase the glycine currents by activating the M3-AChRs and IP3/Ca2+/PKC pathways.

[Analysis of GCDH gene variant in a child with Glutaric aciduria type I].

OBJECTIVE: To explore the genetic basis for a neonate affected with Glutaric aciduria type I (GA-I). METHODS: Targeted capture and high-throughput sequencing was carried out for the proband and her parents. Candidate variants were verified by Sanger sequencing. RESULTS: The proband was found to harbor compound heterozygous variants of the GCDH gene, namely c.523G>A and c.1190T>C, which was derived from her father and mother, respectively. CONCLUSION: The compound heterozygous variants of the GCDH gene probably underlay the GA-I in the patient.

Orexin-A potentiates glycine currents by activating OX1R and IP3/Ca2+/PKC signaling pathways in spinal cord ventral horn neurons.

Orexin-A/B modulates multiple physical functions by activating their receptors (OX1R and OX2R), but its effects in the spinal cord motor control remain unknown. Using acute separation (by digestive enzyme) of cells and patch-clamp recordings, we aimed to investigate the effect and mechanisms of orexin-A on the glycine receptors in the spinal cord ventral horn neurons. Orexin-A potentiated the glycine currents by activating OX1R. In Ca2+-free extracellular solution, orexin-A still increased the glycine currents. While, the orexin-A-induced potentiation was blocked when Ca2+ was chelated by internal infusion of BAPTA, and the orexin-A effect was abolished by the IP3 receptor antagonists heparin and Xe-C. The PKC inhibitor Bis-IV nullified the orexin-A effect. In addition, orexin-A did not cause a further enhancement of the glycine currents after bath application of the PKC activator PMA. In conclusion, after OX1R is activated, a distinct IP3/Ca2+-dependent PKC signaling pathway, is likely responsible for the orexin-A potentiation on glycine currents in the spinal cord ventral horn neurons.

[Etomidate reduces excitability of the neurons and suppresses the function of nAChR ventral horn in the spinal cord of neonatal rats].

OBJECTIVE: To investigate the effects of etomidate on electrophysiological properties and nicotinic acetylcholine receptors (nAChRs) of ventral horn neurons in the spinal cord. METHODS: The spinal cord containing lumbosacral enlargement was isolated from 19 neonatal SD rats aged 7-12 days. The spinal cord were sliced and digested with papain (0.18 g/30 mL artificial cerebrospinal fluid) and incubated for 40 min. At the ventral horn, acute mechanical separation of neurons was performed with fire-polished Pasteur pipettes, and perforated patch-clamp recordings combined with pharmacological methods were employed on the adherent healthy neurons. In current-clamp mode, the spontaneous action potential (AP) of the ventral horn neurons in the spinal cord was recorded. The effects of pretreatment with different concentrations of etomidate on AP recorded in the ventral horn neurons were examined. In the voltage-clamp mode, nicotine was applied to induce inward currents in the ventral horn neurons, and the effect of pretreatment with etomidate on the inward currents induced by nicotine were examined with different etomidate concentrations, different holding potentials and different use time. RESULTS: The isolated ventral horn neurons were in good condition with large diverse somata and intact processes. The isolated spinal ventral horn neurons (n=21) had spontaneous action potentials, and were continuously perfused for 2 min with 0.3, 3.0 and 30.0 µmol/L etomidate. Compared with those before administration, the AP amplitude, spike potential amplitude and overshoot were concentration-dependently suppressed (P < 0.01), and spontaneous discharge frequency was obviously reduced (P < 0.01, n=12). The APs of the other 9 neurons were completely abolished by etomidate at 3.0 or 30 µmol/L. At the same holding potential (VH=-70 mV), pretreatment with 0.3, 3.0 or 30.0 µmol/L etomidate for 2 min concentration-dependently suppressed the current amplitude induced by 0.4 mmol/L nicotine (P < 0.01, n=7). At the holding potentials of - 30, - 50, and - 70 mV, pretreatment with 30.0 µmol/L etomidate for 2 min voltage-dependently suppressed the current amplitude induced by 0.4 mmol/L nicotine (P < 0.01, n=6 for each holding potential). During the 6 min of 30.0 µmol/L etomidate pretreatment, the clamped cells were exposed to 0.4 mmol/L nicotine for 4 times at 0, 2, 4, and 6 min (each exposure time was 2 s), and the nicotinic current amplitude decreased gradually as the number of exposures increased. But at the same concentration, two nicotine exposures (one at the beginning and the other at the end of the 6 min pretreatment) resulted in a significantly lower inhibition rate compared with 4 nicotine exposures (P < 0.01, n=6). CONCLUSIONS: etomidate reduces the excitability of the spinal ventral neurons in a concentration-dependent manner and suppresses the function of nAChR in a concentration-, voltage-, and use-dependent manner.

Antiasthmatic activity of quercetin glycosides in neonatal asthmatic rats.

The present study investigated the anti-asthmatic activity of quercetin glycosides in neonatal asthmatic rats. Rats were divided into four groups: sham (non-asthmatic), asthmatic control, quercetin (25 mg/kg), and quercetin (50 mg/kg). Inflammatory cells in bronchoalveolar lavage fluid (BALF), inflammatory markers, apoptosis, fibrinogen level, prothrombin time, thrombin time, activated partial thromboplastin time, coagulation factor activity, and histopathology were monitored. Quercetin significantly reduced total leukocytes, eosinophils, tumor necrosis factor-α (TNF-α), interleukin (IL-6), nitric oxide (NO), and apoptosis. It also considerably reduced blood coagulation time and coagulation factor activity compared to the controls. The mRNA expression levels of TNF-α, IL-6, and inducible nitric oxide synthase (iNOS) were elevated in asthmatic rats by 1.3-, 1.04-, and 1.1-fold, respectively. However, treatment with 50 mg/kg quercetin glycosides significantly reduced the mRNA expression of TNF-α, IL-6, and iNOS by more than 40%. Quercetin considerably reduced the protein expression of iNOS. Airway and blood vessel narrowing, as well as the accumulation of eosinophils in the lungs were observed in neonatal asthmatic rats. However, treatment with quercetin glycosides significantly reduced inflammation and eosinophil infiltration. In summary, quercetin glycosides significantly attenuated levels of inflammatory markers, demonstrating its protective effects against neonatal asthma in rats.