2025-09-20 2025, Volume 3 Issue 3

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  • REVIEW
    Rong Han, Jie Zhao, Chengjun Yu, Ling Wang, Long Chen, Yang Hu, Shengde Wu

    The regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP with rituximab (R-CHOP) is the first-line treatment for non-Hodgkin lymphoma (NHL). NHL patients treated with CHOP/R-CHOP have a high risk of reproductive adverse events. The aim of this article was to evaluate the reproductive toxicity of regimens and make further suggestions on reproductive protection. We systematically searched with appropriate terms from January 1980 to June 2021 for observational studies in patients treated with CHOP/R-CHOP, without any language restriction. We conducted meta-analyses of one-sample proportions of patients suffering reproductive adverse events after using CHOP/R-CHOP. In addition, subgroup analyses were performed to determine the effect of sex. Nine articles involving 331 patients were included in the meta-analysis, and the pooled proportion of reproductive adverse events was computed to be 22.3% (95% confidence interval [CI] 11.4%–33.2%; heterogeneity test Q = 65.3; τ2 = 0.0231; I2 = 87.70%; p < 0.001) using the random-effects model. And, the pooled proportion of male gonadal toxicity was 29.2% (95% CI 11.0%–47.4%; heterogeneity test Q = 46.65; τ2 = 3.055; I2 = 89.3%; p < 0.0001). The pooled proportion of female gonadal toxicity was 16.5% (95% CI 8.5%–24.5%; heterogeneity test Q = 18.6; τ2 = 0.0112; I2 = 67.8%; p = 0.005). The findings suggest that NHL patients have a relatively high risk of reproductive adverse events after treatment with CHOP/R-CHOP. Men are more likely to have gonadal damage than women. Evaluation of reproductive function is particularly necessary both before and after treatment. Some reproductive protection strategies implemented for patients who want to preserve their fertility.

  • RESEARCH ARTICLE
    Yu Deng, Bing Hu, Yingxue Zou, Zhengxiu Luo, Guangli Zhang, Jinhai Ma, Changshan Liu, Xiaoyan Dong, Huifen Zi, Chuangli Hao, Rongjun Lin, Xiangrong Zheng, Bingfei Li, Fenhua Chen, Mei Fang, Weimin Tian, Zhiqiang Zhuo, Deyu Zhao, Zhimin Chen, Yuejie Zheng, Jingyang Zheng, Yong Yin, Qiuyu Tang, Liqun Wu, Li Gu, Jinzhun Wu, Liyi He, Tao Ai, Ning Wang, Minjun Zhang, Hailin Zhang, Hanmin Liu, Youxiang Zhang, Jianguo Hong, Zhiying Han, Yunbo Mo, Hongmei Qiao, Zhiliang Tian, Zengni Li, Quan Lu, Enmei Liu

    This study aimed to establish a registry database of different treatment modalities for lower respiratory tract infections (LRTIs) in Chinese children, thereby filling gaps in knowledge on clinical characteristics, treatment modalities, and rational drug use in relation to LRTIs in Chinese children, and providing large amounts of continuous, complete, scientific, and objective clinical data, and an information exchange platform. Multicenter data from these children's clinical visits were collected, pooled, and analyzed using medical informatics and statistical techniques to explore their potential value. The database was preliminarily established and a real-world study cohort was constructed based on a total of 4805 patients registered in this database. Pneumonia was identified as the most common type of LRTIs (72.44%), followed by acute bronchitis (20.71%). The mean age of the enrolled children with LRTIs was 3.26 ± 2.84 years, and boys accounted for 59.21% of the samples. Among the enrolled children, pneumonia and acute bronchitis had the highest incidence in children aged 1–3 years (27.44%) and those aged 3–6 years (34.16%), respectively. In this national, multicenter, observational database of LRTIs in children, the real-world characteristics and treatment modalities for LRTIs in Chinese children are elucidated. This database will help improve the research efficiency of clinicians and facilitate the exploration of underlying clinical patterns in real-world medical big data.

  • RESEARCH ARTICLE
    Wenjie Wu, Fengxia Ding, Yan Li, Zhou Fu

    Asthma is a chronic airway inflammatory disease characterized by reversible airflow limitation and airway hyperresponsiveness, which requires long-term drug treatment and management. It is very important to study the etiology and pathogenesis of asthma for clinical asthma prevention and treatment. In this study, to understand the correlation between C-X-C motif chemokine ligand 14 (CXCL14) in bone marrow dendritic cells (BMDCs) and antigen presentation of asthma dendritic cells (DCs), an in vitro model of BMDCs was constructed for RNA sequencing (RNA-seq). The changes of CXCL14 in BMDCs after house dust mites (HDM) stimulation were evaluated. Finally, evaluated the inflammation of the lung tissue in mice, and the expression of costimulatory molecules on the DCs surface in the lung tissue was analyzed by flow cytometry. The results showed that CXCL14 was upregulated in BMDCs after HDM stimulation, and its function was related to signal molecule interaction and the immune system. The expression of CXCL14 was increased in the HDM-induced allergic asthma model. Knockdown of CXCL14 reduced the expression of costimulatory molecules CD86, CD80, and major histocompatibility complex II on the surface of DCs in the lung tissue of mice, induced immune tolerance, and reduced lung inflammatory cell infiltration and inflammatory factor levels, providing new ideas and theoretical basis for the clinical treatment of bronchial asthma.

  • RESEARCH ARTICLE
    Anna Clebone

    Trainees in several medical disciplines are expected to achieve competence in neonatal resuscitation. Managing the neonatal airway requires faculties in mask ventilation. Many trainees, however, have limited clinical experience with this skill. An algorithmic method incorporating the steps an airway expert would use for neonatal mask ventilation was designed. The goal of teaching this system, the “Five Breath Method,” is to assist trainees with learning and incorporating the steps of neonatal mask ventilation into clinical practice. We hypothesized that for pediatric residents, participating in a teaching session on the Five Breath Method would significantly decrease the time to achieve ventilation (“air entry”) in a resuscitation scenario. A pilot study was completed on the Five Breath Method with 23 pediatric residents as subjects. Training in the Five Breath Method reduced the time required to achieve air entry using a neonatal simulator. Subjects required 57 [29–149 and 13–180] seconds (median [interquartile range and minimum–maximum]) before the teaching session and 16 [10–35 and 8–60] seconds after learning the Five Breath Method; Z = −4.11, and P < 0.001. For the 14 of the original subjects who were able to participate in the follow-up study 2–5 months later, 24 [22–38 and 12–69] seconds (median [interquartile range and minimum–maximum]) were required to achieve air entry in the identical experimental scenario. This showed an improvement in time to air entry when compared to that before training; Z = −2.42, and P = 0.01552. This study showed that as little as 10 min of training could drastically improve skills. Learning the Five Breath Method also led to retention of skills over time.

  • REVIEW
    Divya Tadanki, Pranitha S. Kaza, Elliana Meisinger, Ariana Syed, Asha Johnson, Garen Bainbridge, Michelle Cho, Chikaima Anigbogu, Gargi Gupta

    Maternal stress impacts millions of pregnant women across the globe each year and refers to mental or psychological stress that occurs during the prenatal period. Although it remains known that maternal stress can negatively impact maternal health, the downstream effects of stress on fetal and infant development in the long-term are unclear. This leaves a gap in understanding epigenetic factors that impact growth and development, highlighting the need to address potential developmental delays in early childhood. Review of the literature indicates debate over the effect of maternal stress on cognitive development and whether maternal stress is a mediator or causal factor in fetal development. Although evidence suggests that maternal stress disrupts the functional connectivity of the amygdala, information on the sub-regions of the brain impacted by prenatal stress exposure remains unknown. Studies focusing on environmental disasters and war have also indicated adverse impacts on fetal development, additionally emphasizing a greater need for representation in future research. Timing of fetal exposure to stressors also impacts different domains of development. The Georgia OASIS platform was utilized to investigate variations in reported pregnancies, reported fetal mortality rate, and Perinatal Periods of Risk (PPOR) during the years 2013–2023. Increases in fetal mortality were anticipated to be associated with decreases in the rates of maternal, newborn, and infant care. Although evidence exists to support this hypothesis, causation cannot be established; however, the poor state of maternal healthcare in Georgia warrants further investigation of the barriers to healthcare to improve fetal and infant health outcomes statewide.

  • RESEARCH ARTICLE
    Yu Wang, Peng Hong, Zhiqiang Gao, Wei Ma, Zaihong Hu, Jie Lin, Kongkong Cui, Qinlin Shi, Xiao-Mao Tian, Guanghui Wei

    Rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma with 5-year survival below 30% in high-risk/metastatic cases, was investigated through integrated bioinformatics analysis (identifying 269 conserved differentially expressed genes in GEO datasets GSE28511/GSE141690) and experimentally validated thiostrepton (TST), a ribosomal-targeting antibiotic, as a potent therapeutic candidate via Connectivity Map analysis (p < 0.05, score ≈ −1). In-vitro studies demonstrated TST's dose-/time-dependent suppression of RMS proliferation (IC50 4.986–9.764 μmol/L), migration and invasion, G0/G1 cell cycle arrest, and apoptosis induction. In vivo, TST (3.4 mg/mL, 4 weeks) significantly inhibited tumor growth (p < 0.05 vs. phosphate buffered saline [PBS]) without organ toxicity. RNA sequencing identified the phosphatidylinositol 3-kinase/protein kinase B (PI3K-AKT) pathway as the primary suppressed pathway (False Discovery Rate [FDR] < 0.05), with concurrent downregulation of downstream regulators (AKT, JAK, CDKs). This was confirmed by PI3K activator 740 Y-P rescue experiments, which partially reversed the effects of TST (p < 0.05). These findings establish TST as a multi-mechanism PI3K-AKT inhibitor for refractory RMS while validating Connectivity Map (Cmap)-driven drug repurposing for pediatric oncology.

  • RESEARCH ARTICLE
    Ranganatha A. Devaranavadagi, Gayatri Sasikumar, Pavitra Gangadharan Chandrasekaran, Netra S. Kannur, H. A. Venkatesh, Suma Sriramanan, C. N. Radhakrishnan, Jayashree S. Simha, Karthik Nagesh

    Neonates, particularly those born preterm, have a higher incidence of inguinal hernia and are at increased risk of cardiopulmonary complications associated with general anesthesia. To mitigate these risks, spinal anesthesia has been adopted in our institution for over two decades as the preferred technique for inguinal hernia repair in neonates. This retrospective study presents a 6-year experience with neonatal spinal anesthesia and includes both term and preterm infants undergoing inguinal surgery. We specifically analyzed cases in which spinal anesthesia was used in neonates with a postconceptional age below 50 weeks. Nineteen patients underwent inguinal surgery under spinal anesthesia in this timeframe. The gestational age at birth ranged from 27 to 38 weeks. The postmenstrual age at the time of surgery ranged from 35 to 46 weeks. The birth weight ranged from 740 to 3300 g, whereas the weight at surgery ranged from 1550 to 4900 g. A 26G hypodermic needle was used to give the spinal block, and 0.2 mL/kg of 0.5% heavy bupivacaine was injected. No cases required respiratory support and/or inotropic support during the procedure and postoperatively. None had apnea during/after surgery, including the four cases of bronchopulmonary dysplasia. None required general anesthesia. Spinal anesthesia for inguinal hernia repair is a safe and efficient method that obviates the necessity for NICU admission or any escalation in respiratory care, including in the cases of bronchopulmonary dysplasia.

  • EDITORIAL
    Karen Spruyt
  • RESEARCH ARTICLE
    Yinming Song, Daiyin Tian, Sha Liu, Fangjun Liu, Jingyue Liu, Ying Li, Li Yan

    This is a retrospective study. In order to investigate the effect of specific immunotherapy on the improvement of lung function and symptoms in children with bronchial asthma, 256 children with bronchial asthma were selected and divided into an experimental group and a control group according to whether they chose to use sublingual specific immunotherapy or not. The control group was given basic drug therapy, and the experimental group was given specific immunotherapy on the basis of basic drug therapy. Differences between the two groups were compared in terms of lung function, efficacy, and asthma medication dose. The results showed that peak expiratory flow (PEF), maximum expiratory flow at 25% of forced vital capacity (MEF25), maximal mid-expiratory flow curve (MMEF), maximum expiratory flow at 75% of forced vital capacity (MEF75), maximum expiratory flow at 50% of forced vital capacity (MEF50), and airway hyperresponsiveness improved in both groups after 1 year of treatment (P < 0.05), and the result of experimental group was better than that of the control group (P < 0.05). This study shows that sublingual specific immunotherapy combined with inhaled corticosteroid therapy has positive therapeutic effects on asthma patients, which can reduce the dose of medication used in asthma patients and improve symptoms.

  • RESEARCH ARTICLE
    Natalia Builes, Byron E. Piñeres-Olave, Laura Niño-Serna

    Hematopoietic stem cell transplant (HSCT) is associated with some complications requiring advanced support in the pediatric intensive care unit (PICU). However, the outcome of children requiring admission to a PICU following HSCT in middle-income countries (MICs) are limited. One hundred and four children undergoing hematopoietic stem cell transplantation at a bone marrow transplant service in Colombia from January 2012 to June 2019 were enrolled. Baseline characteristics and clinical courses were described. In addition, we compared some characteristics of patients who survived or died in the PICU through a bivariate analysis. Twenty five PICU admissions were reported. Sixty-four percent survived to be discharged from any PICU admission. Immunodeficiency was the most common underlying disease among patients admitted to the PICU (33%). Respiratory problems (12/25, 48%), and cardiovascular instability (10/25, 40%) were the most common reasons for admission. Cardiovascular support was the most common PICU treatment (21/25, 84%), followed by respiratory support (18/25, 72%). We found that children who require admission to PICU after an allogeneic hematopoietic stem-cell transplantation (Allo-HSCT) present a high mortality rate. Invasive respiratory support, higher vasoactive-inotropic score, renal replacement therapy, and the presence of multi-organ failure were associated with mortality.

  • RESEARCH ARTICLE
    Rashid Katamesh, Katharina Witt, Sebastian Ebert

    During hypoxic ischemic encephalopathy (HIE) therapy for neonates, the patient temperature must be kept at 33.5°C as stable as possible throughout the therapy time. Therefore, hypothermia devices with a fluid-circulated temperature-regulating mat have become established. However, therapeutic interventions often require medical personnel to open the mat to reach the patient. This can lead to a loss of thermal regulation due to heat exchange between the patient and environment which can result in a slower or stopped therapy. To mitigate this issue, the wrapping bag TECOtherm Wrabbit was proposed to shield the patient from external temperature fluctuations and maintain therapeutic efficacy. We conducted a laboratory experiment using a test model to evaluate the effectiveness of the wrapping bag under two conditions: with and without TECOtherm Wrabbit, both under dry and moistened states at room temperatures of 21°C and 27°C. The objective was to assess the retention of patient temperature during possible interventions. Results indicated a significant decrease in temperature when the wrapping bag was not used. Conversely, the use of the wrapping bag demonstrated a slight but controlled temperature change. These findings suggest that the wrapping bag can effectively aid in maintaining patient temperature during necessary clinical interventions. Further clinical research is warranted to validate the application of wrapping bag in maintaining neonatal temperature stability during hypothermic therapy.

  • RESEARCH ARTICLE
    Tian Tian, Chong Huang, Lusheng Li

    Pediatric high-grade gliomas (pHGG) were first defined as a distinct entity in the 2021 fifth edition of the WHO classification of tumors of the central nervous system. These tumors, designated primarily as Grade 4, include the following subtypes: (1) diffuse midline glioma with H3-K27 alterations (DMG, H3-K27M), (2) diffuse hemispheric glioma with H3-G34 mutations (DHG, H3G34M), and (3) diffuse pediatric-type high-grade glioma with wild-type H3 and isocitrate dehydrogenase (pHGG, H3-WT/IDH WT). Clinically, pHGGs are known for their poor outcomes and marked tumor heterogeneity. Despite this, the characteristics of the tumor microenvironment (TME) and the processes governing tumor cell lineage transitions remain incompletely understood. In this study, we used single-cell RNA sequencing (scRNA-seq) to analyze pHGG tumor cells (excluding infant-type hemispheric gliomas). Through comprehensive bioinformatic approaches—including cell proportion analysis, Gene Ontology (GO) enrichment, metabolic activity inference via scMetabolism, proliferation gene scoring, stemness assessment by CytoTRACE2, SCENT, and pseudotime trajectory analysis with Monocle2—we thoroughly investigated the TME features and heterogeneity of these aggressive brain tumors. Our findings highlight the presence of oligodendrocyte precursor cell (OPC)-like subpopulations, with epidermal growth factor receptor (EGFR)-expressing OPC-like cells emerging as a potential tumorigenic origin in diffuse midline gliomas due to their distinct stemness properties. Notably, platelet-derived growth factor receptor alpha (PDGFRA)-positive cells exhibit high specificity in DMG, suggesting greater diagnostic and therapeutic potential than EGFR. Next-generation sequencing (NGS) and multiplex immunofluorescence analyses confirmed their distinct expression pattern, supporting PDGFRA as a key molecular marker. Moreover, OPC-like cells at different differentiation states may drive lineage transitions in DMG. Together, these findings enhance our understanding of pHGG—especially DMG—and point to new avenues for targeted therapy.

  • CASE REPORT
    Zhiwei Yu, Yuan Xue, Hanyu Luo, Yuhang Li, Siqi Hong, Jiannan Ma, Li Jiang