Translational pediatrics最新文献

Background: As one of the most common causes of community-acquired pneumonia in children, the prevalence of mycoplasma pneumonia (MPP) has long been underestimated. This study aimed to analyze children's severe MPP (SMPP) by examining laboratory characteristics and identifying high-risk factors.

Methods: Clinical data from 447 hospitalized children with MPP were retrospectively analyzed. Patients were categorized into ordinary MPP and SMPP groups. Initial laboratory results on admission were compared between groups, and risk factors for SMPP were assessed using receiver operating characteristic (ROC) and logistic regression analyses.

Results: Children with SMPP exhibited significantly higher levels of neutrophils, neutrophil/lymphocyte ratio (NLR), C-reactive protein (CRP), interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), and lactate dehydrogenase (LDH), along with lower lymphocyte, albumin (ALB), and prealbumin (PAB) levels compared to the ordinary MPP group (all P<0.05). SMPP children also had a higher incidence of multiple pathogens (P<0.05). ROC analysis identified cutoff values for ESR, LDH, IL-6, CRP, neutrophil percentage, and NLR, with corresponding areas under the curve (AUCs) indicating their predictive values for SMPP. A combined analysis of these factors yielded an AUC of 0.732 (P<0.05). Multivariate logistic regression confirmed ESR >35.50 mm/h, LDH >360.50 U/L, IL-6 >20.28 pg/mL, and CRP >9.74 mg/L as independent high-risk factors for SMPP (P<0.05).

Conclusions: ESR, LDH, IL-6, CRP, neutrophil percentage, and NLR are valuable predictors for early identification of SMPP in children. These findings provide essential insights for clinical management aimed at assessing and intervening in prognosis.

Background: Corrected age entails determining the age of premature infants by adjusting their gestational age to 40 weeks. Research on corrected age in relation to neurodevelopment is limited, both domestically and internationally, resulting in a lack of consensus and recommendations regarding the appropriate termination of the neurodevelopmental corrected age. This study aimed to assess the neurodevelopmental catch-up status of premature infants with varying gestational ages and to identify appropriate termination criteria for the corrected age of neurodevelopment.

Methods: The study included 1,579 premature infants without high-risk factors and 8,441 full-term infants receiving care at the child health clinics of the Second Affiliated Hospital of Army Medical University, Chongqing Health Center for Women and Children, and Maternal and Child Health Care Hospital of Wanzhou District, Chongqing between January 1, 2018, and March 1, 2023. Infants were grouped based on gestational age into early, middle, and late premature infants, as well as full-term infants. Over a 48-month period, the developmental quotient (DQ) of each functional area on the Gesell Developmental Scale was compared across groups.

Results: There were no statistically significant differences in DQ of all functional areas between late premature infants and full-term infants at 36 months of age (all P>0.05). In contrast, some developmental functional areas in middle- and early-premature infants and full-term infants exhibited significant differences at 36 months of age; however, by 48 months of age, these differences were no longer significant (all P>0.05). The DQ of all functional areas in the late, middle, and early premature infant groups demonstrated a catch-up trend from 6 to 48 months of chronological age (all P<0.05).

Conclusions: The termination age for neurodevelopmental correction in premature infants may continue beyond 36 months of age, with longer correction time required for those born at younger gestational ages.

Background: The development of the testes is a tightly regulated process, requiring the coordination of multiple genes. Mutations in these genes can result in 46,XY gonadal dysgenesis. NR0B1, located at Xp21, is a gene expressed in the developing adrenals, gonads, hypothalamus, and pituitary gland. Duplication of this area causes dosage sensitive male-to-female sex reversal and involves multisystem abnormalities. The heterogeneity in clinical phenotypes is attributed to variations in the size of the duplicated segments. Herein, we present a case with 46,XY disorders of sex development and muscular dystrophy due to Xp21 duplication.

Case description: A 5-month-old boy was admitted to our hospital due to gonadal dysgenesis. The patient was born to a healthy couple after 37+4 weeks of pregnancy and with a natural delivery. In the course of the disease, the child showed marked growth retardation, elevated muscle enzymes and liver enzymes. During the follow-up, he developed hypotonia and low muscle strength. Chromosomal microarray analysis (CMA) testing uncovered a 7.79 Mb duplication at Xp21 in both the patient and his mother, encompassing 30 coding genes, including the NR0B1 and DMD genes.

Conclusions: The duplication of Xp21 can result in a rare genetic disorder characterized by various abnormalities in males, including short stature, mental retardation, muscular dystrophy, and gonadal dysplasia. These symptoms are often overlooked and misdiagnosed. Targeted gene detection should be completed to enable early diagnosis and intervention to improve prognosis. This study has enhanced clinicians' understanding of the disease.

Background: The circulation in free flap is mainly studied on blood perfusion, but lack of exploring contributory factor of lymphatic drainage. This study aimed to monitor lymphatic reconstitution of free latissimus dorsi (LD) flaps for lower extremity defects repair, using indocyanine green (ICG) lymphography and assessing its relationship with post-operative flap edema.

Methods: Patients who underwent lower extremity defects repair with free LD flap between January 2021 and April 2024 were included. The inclusion criteria were as follow: (I) lower extremity defects; (II) wound repaired by free LD flap; (III) more than 6 months of follow-up. ICG lymphography was performed to monitor lymphatic reconstitution at different timepoints (postoperative 3^rd day, 7^th day, 10^th-14^th day, 1^st month, and 3^rd month). Changes in flap limb circumference were recorded at different timepoints (operation day, 3^rd day, 7^th day, 14^th day, 1^st month, and 3^rd month).

Results: Of the 12 patients examined (mean age: 10.3±2.7 years old, range from 7 to 16 years old; male to female ratio: 7:5), LD flap edema reached its peak on 3^rd day postoperatively, and involuted in one week. Lymphedema was initially observed between 10 and 14 days (average: 11.5±1.7 days). Flap swelling was not found decreased from 7^th day to 1st month, but involuted remarkably between 1^st month and 3^rd month postoperatively. The overall time of spontaneous lymphatic reconstitution in LD flap ranged from 11 to 16 weeks (average: 12.8±1.6 weeks), and flap edema resolution ranged from 12 to 16.5 weeks (average: 13.6±1.3 weeks).

Conclusions: Lymphedema forms without obvious decrease of flap swelling in plateau period, and flap edema resolves gradually after lymphatic reconstitution, which is crucial to edema resolution of free LD flap, and the findings in this research may aid in understanding option of symptomatic management in flap edema.

Background: In recent years, the survival rate of preterm infants has significantly improved due to the application of pulmonary surfactant (PS) and advancements in lung-protective mechanical ventilation strategies. However, this has been accompanied by an increased incidence of complications, particularly lung diseases triggered by elevated reactive oxygen species (ROS) induced by hyperoxia. The primary mechanism of hyperoxic lung injury (HLI) involves the excessive production of ROS within cells and the aggregation of inflammatory cells. Currently, no effective prevention or treatment methods are available. Ferroptosis, a newly identified form of cell death, is closely linked to ROS accumulation and is likely involved in HLI. Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates both HLI and ferroptosis, and targeting Nrf2 to inhibit ferroptosis may represent a key therapeutic approach for treating HLI. This study aimed to investigate the involvement of ferroptosis in HLI and to elucidate the regulatory role of Nrf2.

Methods: We employed the human pulmonary microvascular endothelial cell (HPMEC) model of hyperoxia exposure and corresponding intervention groups. Mitochondrial morphological alterations within HPMECs exposed to hyperoxia and various control groups were examined using transmission electron microscopy (TEM). Cell viability was assessed via the Cell Counting Kit-8 (CCK-8) assay, whereas intracellular ROS levels were quantified using the dichlorodihydrofluorescein diacetate (DCFH-DA) probe. Furthermore, the expression levels of GPX4 and Nrf2 were analyzed through quantitative polymerase chain reaction (qPCR) and western blot techniques.

Results: Relative to the control group, the HPMECs subjected to hyperoxic conditions exhibited diminished viability, heightened ROS levels, decreased GPX4 expression, and increased Nrf2 expression. These cells also demonstrated mitochondrial morphological alterations characteristic of ferroptosis, including reduced mitochondrial cristae and shrinkage. The application of a ferroptosis inhibitor mitigated cellular damage, lipid peroxidation, and the morphological manifestations of mitochondrial ferroptosis, whereas Nrf2 inhibitor ML385 reversed this effect.

Conclusions: Ferroptosis appears to contribute to the pathogenesis of HLI, with Nrf2 serving a protective function by mitigating ferroptosis.

Background: Neonatal intestinal malrotation complicated by midgut volvulus is a serious and common life-threatening complication. When the midgut volvulus is prolonged or severe, it can lead to secondary necrosis of the entire midgut, with high mortality rates. Therefore, improving understanding the clinical characteristics of this condition is necessary to facilitate early diagnosis and treatment. Herein, we report a case of congenital intestinal malrotation and necrosis of the midgut volvulus in a newborn.

Case description: The patient was admitted to the hospital with vomiting, abdominal distension, and bloody stools. An emergency laparotomy revealed a large-area necrosis of the small intestine and torsion of the mesenteric root. External intestinal placement was performed initially, followed by a secondary laparotomy 72 hours later, which showed complete necrosis of the jejunum but recovery of the ileum. Duodenal and ileal ultra-high position fistulas were created, which were managed by intestinal fluid return and milk micropump feeding. Following that, fistula formation was performed 84 days after the second operation, and full enteral feeding was quickly achieved. The growth and development of the child were good at later follow-ups.

Conclusions: The condition of the intestine in severe cases of neonatal intestinal malrotation combined with necrosis of midgut volvulus is unpredictable. The comprehensive management of operation timing, operation method, and close cooperation between neonatal physicians, surgeons, and nursing teams can greatly improve the success rate of treatment.

Background: Infantile epileptic spasms syndrome (IESS) is a common epileptic syndrome in infancy. Current first-line treatments include adrenocorticotropic hormone (ACTH), corticosteroids and vigabatrin, with early control of epileptic spasms potentially benefiting long-term outcomes, such as improved psychomotor development. Early treatment, which means the prompt use of first-line treatments, is crucial for achieving an initial response in IESS. However, to date, no clear definition of the specific timeframe that constitutes early treatment has been identified. The objective of this study is to perform a secondary analysis of our previously published IESS cohort data to determine a suitable lead time.

Methods: An analysis was conducted using a cohort of 263 children with IESS who had previously received ACTH first-line treatment. This study investigated whether intervening within a certain treatment time window could potentially increase or decrease the likelihood of a short-term response.

Results: Out of the 263 children with IESS, 108 achieved a short-term response. The lead time of the response group was significantly shorter than that of the non-response group [1.50 (interquartile range, 1.00, 3.00) vs. 2.00 (interquartile range, 1.00, 5.00) months; P=0.003]. A restricted cubic spline graph with several adjusted variables, including time of first spasm and aetiological classification, showed a significant linear relationship between lead time and short-term response and a non-linear trend (inverted U-shaped curve), with a significant inflection point at 1.6 months. Using 1.5 months as the cutoff and dichotomising lead time, the adjusted logistic regression results showed that in children with a lead time >1.5 months, the likelihood of a short-term response decreased with increasing lead time [odds ratio (OR) =0.59, 95% confidence interval (CI): 0.33-0.92, P=0.041), whereas children with a lead time ≤1.5 months showed no significant association between lead time and short-term response (OR =1.03, 95% CI: 0.72-1.47, P=0.89).

Conclusions: For children with IESS, initiating first-line treatment within 1.5 months of the onset of spasms is recommended. For those who start first-line treatment after more than 1.5 months from the onset, the likelihood of a short-term response may significantly decrease as the lead time increases.

Background: Observational studies on the association between gestational diabetes mellitus (GDM) during pregnancy and pediatric neurological disorders (PNDs) such as cerebral palsy (CP), autism spectrum disorders (ASD), and epilepsy (EP) in offspring have yielded mixed findings, creating ambiguity in causal interpretations. The direct link between GDM and these PNDs remains unclear. Elucidating this connection is vital for developing effective early intervention strategies during pregnancy to mitigate the risk of PNDs in the offspring. This study utilizes a two-sample (2-sample) Mendelian randomization (MR) approach to investigate the causal relationship between GDM and its impact on CP, ASD, and EP in offspring.

Methods: We employed 2-sample MR using 6 single nucleotide polymorphisms (SNPs) strongly associated with GDM. Summary-level data for CP, ASD, and EP were obtained from the Integrative Epidemiology Unit (IEU) Open Genome-Wide Association Study (GWAS) project, encompassing sample sizes of 217,278, 46,351, and 463,010, respectively. The robustness of our findings was assessed using the inverse variance-weighted (IVW) method along with additional sensitivity analyses.

Results: The results demonstrate that GDM is associated with a higher risk of offspring CP as determined by the IVW method [odds ratio (OR): 1.74; 95% confidence interval (CI): 1.27-2.37; P<0.001]. In contrast, no association was observed between GDM and ASD or EP. Additionally, alternative methods for sensitivity analyses showed consistent results, and there was no pleiotropy detected using MR-Egger regression (P=0.48).

Conclusions: This study provides strong evidence supporting a positive causal relationship between genetically predicted GDM and the increased risk of offspring CP, with no observed correlation found with ASD or EP.