Background: Mendelian randomization (MR) has been used to identify drug targets in many conditions. Height is a classic complex trait affected by genetic and early-life environmental factors. No systematic screening has been conducted to identify drugs that interact with height. We investigated the causal relationship between genes and height, and systematically screened for interactive drugs that may promote or delay growth.
Methods: We performed MR using summary statistics from the Genetic Investigation of ANthropometric Traits consortium (N=253,288), the UK Biobank (N=461,950), and the BioBank Japan Project (N=159,095). Gene expression-single-nucleotide polymorphism associations represented by cis-expression quantitative trait loci data were obtained from the Genotype-Tissue Expression study and were used as genetic instruments. We performed annotation and enrichment analyses of the genes. Interactive drugs were identified through drug-gene interactions.
Results: Of the 27,094 genes screened, 209 had causal associations with height, including genes associated with height and short stature phenotypes (AMZ1, GNA12, NPPC, UQCC1, and ZBTB38), genes associated with height in a few studies (ANKIB1, CEP250, DCAF16, HIST1H4E, and HLA-C), and genes without previous evidence (BTN2A2 and RBMS1P1). Enrichment analysis showed that transcriptional regulation by RUNX1 was the most enriched pathway. Interactive drugs were identified, including amoxicillin, atenolol, infliximab, colchicine, propionyl-L-carnitine, BMN-111, and tamoxifen, which were known to have a positive effect on height. We also identified drugs that had a negative effect on height, including antineoplastic drugs, corticosteroids, and antiepileptic drugs. Moreover, many interactive drugs have not been previously reported to be associated with height.
Conclusions: Our results suggest that many genes have causal effects on height. By interrogating drug-gene interactions, interactive drugs have been identified as having both positive and negative effects on growth, which would help make clinical decisions.
Background: Esotropia is a common pediatric ophthalmologic disorder that, if left untreated, can have a significant impact on the binocular visual function and appearance of the child. Binasal occlusion (BNO) is a non-surgical measure to alleviate the impact of esotropia. But there is no consistent theoretical basis for BNO and its therapeutic efficacy has been controversial. This study aimed to investigate the effect of BNO in the treatment of children with esotropia.
Methods: We performed a retrospective review of children with multiple types of esotropia who still had symptoms of obvious esotropia or the presence of visual diplopia after full refraction correction at the Affiliated Hospital of Yunnan University Hospital from October 2022 to September 2023. All the children were given BNO. Vision function and strabismic degree were examined before and after 3 months of BNO. The data were analyzed by Wilcoxon signed-rank test and Fisher's exact test.
Results: The mean value of the strabismus before BNO was significantly different from the mean value of the strabismus after BNO for 3 months, including near strabismus [25.22±18.25 vs. 9.63±11.92 prism diopters (PD); P<0.001], and distance strabismus (23.65±17.45 vs. 9.27±12.47 PD; P<0.001). Twenty-six cases were markedly corrected, 6 cases were effectively corrected, 9 cases were invalid. There was no significant difference in the efficacy of BNO between the various types of esotropia (F=8.333; P=0.15). Fifteen children had diplopia before, and 14 children reported the disappearance of diplopia after 3 months, with an effective rate of 93.33%.
Conclusions: BNO is an effective non-surgical treatment measure, which can effectively reduce the strabismus degree of many types of esotropia and improve the visual double-image situation, providing a good basis for the establishment of the subsequent visual function.
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: 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: 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 3rd day, 7th day, 10th-14th day, 1st month, and 3rd month). Changes in flap limb circumference were recorded at different timepoints (operation day, 3rd day, 7th day, 14th day, 1st month, and 3rd 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 3rd 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 7th day to 1st month, but involuted remarkably between 1st month and 3rd 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.
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