Uveal melanoma (UM) is the most common primary ocular malignancy in adults, and the 5-year disease-related mortality rate is 30%. MAL proteolipid family (MALs), including T-cell differentiation protein (MAL), T-cell differentiation protein 2 (MAL2), and T-cell differentiation protein like (MALL), were involved in the progression and prognosis of many different cancers. However, the role of MALs in UM was not reported. UM samples were extracted from The Cancer Genome Atlas. R software (R3.6.3) was used to comprehensively analyze the roles of the MALs (significance threshold: p < 0.05). MALs mRNA expression was changed in UM tissues. In terms of tumor stage, MAL2 was highly expressed in T4 (p = 0.021). The ROC curves indicated that MAL2 and MALL were prognostic biomarkers for 1- and 3-year survival in UM patients, and MAL2 also could predict 5-year survival for UM patients. Then, the univariable and multivariable analysis showed that MAL2 and MALL were independent prognostic biomarkers. Next, we assessed the immune microenvironment of MALs in UM. MAL had no correlation with B7-H3, but MAL2 and MALL had a positive correlation with B7-H3. Our results revealed that the MAL proteolipid family may be prognostic biomarkers for UM patients and that B7-H3 may be a novel immunotherapy target for UM.

Recently, single-cell RNA sequencing (scRNA-seq) has emerged as a novel and high-resolution technique for identifying cell types, states, and subpopulations. This technique enables researchers to uncover cellular heterogeneity and detect rare cell populations that might be indistinguishable in bulk RNA-seq data. The primary aim of scRNA-seq analysis is to investigate cellular heterogeneity and distinguish distinct cell types or states. scRNA-seq provides a detailed understanding of intercellular differences and diversity by obtaining gene expression data for each individual cell. Moreover, clustering methods in scRNA-seq can be used to group cells bring into subpopulations based on their gene expression patterns, thereby uncovering similarities and differences that assist in identifying and defining cell types. Newly discovered cell types can be validated and named by labeling known cell marker genes. Additionally, scRNA-seq helps in identifying genes specifically expressed at different developmental stages, in various tissue types, or under various disease states. Recently, there has been a growing trend in using single-cell transcriptome sequencing technology for neuroblastoma (NB) research. Through conducting a comprehensive review of relevant articles published thus far, our understanding of NB has been significantly enriched from three critical perspectives: differentiation trajectory, tumor heterogeneity, and immune microenvironment. Firstly, in exploring the differentiation trajectory of NB, we have summarized the tumor’s origin and subsequent directions of differentiation. By elucidating a complete tumor differentiation pathway, we can enhance our understanding of the mechanisms underlying spontaneous tumor regression. Secondly, we have summarized the heterogeneity of tumors, which encompasses different states, cell morphologies, and characteristic genes of NB identified through single-cell sequencing technology. This consolidation of knowledge enhances our understanding of the heterogeneity of NB. Lastly, we have employed single-cell sequencing technology to analyze the immune microenvironment, focusing on the cellular components within the tumor’s surrounding environment and the diverse states of immune cells. This valuable information contributes to the advancement of NB diagnosis, treatment, and prognosis. In conclusion, the application of single-cell sequencing technology in NB research has significantly advanced our understanding of the disease and carries great significance.

Primary immunodeficiency diseases (PIDs) present a heterogeneous group of diseases with aberrant immune response caused by monogenic mutations. Due to the immune dysfunction and dysregulation, PIDs have a wide clinical spectrum such as infections, autoimmunity, autoinflammation, allergy, and malignancies. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized with multiple autoantibodies and multiple organ damage, which could be the predominant phenotype in patients with PIDs. In recent years, the increasing identification of monogenic causes of SLE and PIDs discloses the partially shared genetic background and common pathogenic process. The study of PIDs with SLE-like phenotype paves the way for the exploration of lupus pathogenesis and new perspectives in targeted therapies concurrently.

Neuroblastoma (NB), as a representative of tumors of embryonic origin in children, has specific clinical features. On the one hand, a very small number of NBs may appear to regress on their own. On the other hand, highly malignant NBs can invade the surrounding blood vessels and organs and metastasize to distant bone, bone marrow, and lymph nodes in the early stages of the disease. Based on differential affinities to insulin growth factors (IGFs), insulin growth factor binding proteins (IGFBPs) are classified into two groups: IGF binding proteins (IGFBP1-6) with high-affinity and IGF low-affinity binding proteins, such as IGFBP-related proteins (IGFBP rP1-10). IGFBP are crucial regulators of the bioavailability and function of IGF in metabolic signaling and as modulators of IGF signaling, and their role in NB is gaining increasing attention. In this study, we investigate the involvement of IGFBP family members in the growth and differentiation of NB cells, as well as the potential of IGFBPs as prognostic biomarkers and therapeutic targets for human NB.

Infectious intracranial aneurysm (IIA) and embolic cerebral infarction are well-known devastating complications of children suffering infective endocarditis. In this report, we describe a successfully embolized IIA concurrent with bilateral middle cerebral artery (MCA) occlusion. Unfortunately, a newly formed IIA located in the contralateral MCA bifurcation ruptured at the seventh day following embolization. A 6-month-old female child was admitted to hospital 3 days following acute right limb mobility disorder. An interventional surgery history of congenital heart disease was confirmed. She was immediately started on antibiotic therapy and the computed tomography agiography (CTA) scan showed occlusion of the upper branch of the left MCA. Unfortunately an IIA was located in the distal artery region (DAR) of the ipsilateral anterior cerebral artery. Angiography (digital subtraction angiography) was performed and the DAR IIA was embolized by OnyX-18 with Magic 1.2 Fr. microcatheter. On the sixth day, magnetic resonance imaging during the hospital stay showed reduced infarction area with no other special sign. Desperately, a major seizure with opisthotonos attacked the baby on the seventh day after embolization. An immediate CTA scan showed massive hematoma in the right basal ganglia and a ruptured bifurcate aneurysm of the right MCA. The parents refused positive treatment and discharged in considering the critical situation. It should be noted that IIA can be fast formed anywhere in cerebral artery and dynamic angio-image should be performed as supervision.

The crucial role of ribonucleotide reductase M2 (RRM2) enzyme in cancer occurrence and progression has been well-established, but its specific function and significance in medulloblastoma (MB) remains largely unknown. First, we conducted a bioinformatics analysis of public genomic databases and observed highly expressed RRM2 in MB and an association of high RRM2 expression with adverse outcomes. In addition, by collecting clinical MB specimens for polymerase chain reaction (PCR), western blotting (WB), and immunohistochemistry (IHC), RRM2 was confirmed to be highly expressed in tumor tissues. Furthermore, immunohistochemical analysis linked adverse prognosis to high RRM2 expression. Moreover, knocking down RRM2 significantly inhibited MB cell proliferation, migration, and invasion in vitro. This report is the first to demonstrate the oncogenic role of RRM2 in MB, associated with adverse patient outcomes. Knocking down RRM2 contributes to weakened proliferating, migrating, and invading potentials of MB cells. RRM2 is expected to be a novel prognostic biomarker and therapeutic target for MB.

Ropivacaine is a commonly used local anesthetic for brachial plexus blocks in children, but the minimum effective dose of ropivacaine for interscalene brachial plexus blocks has not been reported. The aim of this study was to determine the 90% minimum effective concentration (MEC90) of ropivacaine for an ultrasound-guided interscalene brachial plexus block (ISB). A total of 155 patients, aged from 1 to 10 years, underwent unilateral surgical procedures on areas of the upper extremity not innervated by the ulnar nerve. The biased coin design up-and-down sequential method (BCD-UMD) was used to determine the MEC90 of ropivacaine for ultrasound-guided ISB. In our study, the initial concentration of ropivacaine was 0.07% in the toddler group and 0.09% in the preschool and school-age groups. During the trial, the concentration of ropivacaine for each subsequent patient was determined by the blocking effect of the previous patient. In case of failure, the concentration for the next patient was increased by 0.01%. Otherwise, the concentration was either decreased by 0.01%, with a probability of 0.11, or kept the same, with a probability of 0.89. Overall, the MEC90 of ropivacaine was 0.104% (95% confidence interval (CI), 0.070%–0.106%) in the toddler group, 0.114% (95% CI, 0.090%–0.117%) in the preschool group, and 0.133% (95% CI, 0.099%–0.136%) in the school-age group. No adverse events occurred. Our study showed that lower concentrations of ropivacaine could provide effective nerve blocks and reduce the risk of local anesthetics.

Human Papillomavirus (HPV) is the most common sexually transmitted infection and is associated with cervical, anogenital, and oropharyngeal cancers. It is crucial to improve vaccination uptake in both genders as primary prevention for these conditions. Pediatricians play an active role in advocating for HPV vaccination and our study aims to assess the level of knowledge, attitudes, barriers, and practices among pediatric trainees and general pediatricians regarding HPV infection and vaccination. A survey-questionnaire was administered to our target groups. It comprised 14 questions regarding demographics of the healthcare provider, knowledge of HPV infection and vaccination, practices and barriers of recommending HPV vaccination, and effective strategies for improving HPV vaccine uptake. Among survey respondents, majority did not recommend for HPV vaccination (66.7%) or receive any enquiry about it (80.6%) within the preceding 12 months. The most common perceived barrier was inadequate knowledge, which was consistent with the misconceptions regarding HPV infection and vaccination that were identified in this survey. Strategies which physicians felt would be most effective in increasing vaccine uptake include educating and providing resources for both physicians and caregivers as well as making the vaccine free. Our study revealed a low advocacy rate for HPV vaccination. Physicians need to be equipped with the knowledge, skills, and resources to better counsel caregivers as well as focus our efforts on vaccinating male patients in order to increase vaccine uptake in both genders.

The involvement of astrocytic connexin 43 (Cx43) in epileptogenesis has been extensively studied through various approaches, yet the underlying mechanism remains enigmatic. In this study, we explored whether astrocytic Cx43 forms hemichannels (HCs) that contribute to seizure progression in temporal lobe epilepsy (TLE) in mice. We focused on how these HCs influence the permeability of the blood-brain barrier (BBB), a crucial factor in the pathophysiology of epilepsy. Immunofluorescence staining and western blot analysis were employed to assess Cx43 expression in kainic acid-induced TLE mice, while BBB permeability was evaluated in TLE mice and those treated with TAT-Gap19 (an astrocytic Cx43 HC inhibitor) using Evans Blue permeation, serum S100β protein quantification, ZO-1 expression, and albumin extravasation into brain parenchyma via western blotting. Furthermore, seizure burden was monitored continuously using telemetric electroencephalography (EEG) and video monitoring in epileptic and TAT-Gap19-treated mice. Results demonstrated a significant increase in Cx43 content in hippocampal tissue in the TLE group, with a pronounced expression around blood vessels. TAT-GAP19 treatment alleviated EEG seizures and BBB permeability in TLE mice. These findings suggest that astrocytic Cx43 HCs in the hippocampus play a crucial role in epileptogenesis and seizure progression by regulating BBB permeability. Targeting Cx43-formed HCs distributed around the neurovascular unit may offer a novel therapeutic approach for epilepsy.

Despite advances in prenatal screening and a notable decrease in mortality rates, congenital heart disease (CHD) remains the most prevalent congenital disorder in newborns globally. Current therapeutic surgical approaches face challenges due to the significant rise in complications and disabilities. Emerging cardiac regenerative therapies offer promising adjuncts for CHD treatment. One novel avenue involves investigating methods to stimulate cardiomyocyte proliferation. However, the mechanism of altered cardiomyocyte proliferation in CHD is not fully understood, and there are few feasible approaches to stimulate cardiomyocyte cell cycling for optimal healing in CHD patients. In this review, we explore recent progress in understanding genetic and epigenetic mechanisms underlying defective cardiomyocyte proliferation in CHD from development through birth. Targeting cell cycle pathways shows promise for enhancing cardiomyocyte cytokinesis, division, and regeneration to repair heart defects. Advancements in human disease modeling techniques, clustered regularly interspaced short palindromic repeats -based genome and epigenome editing, and next-generation sequencing technologies will expedite the exploration of abnormal machinery governing cardiomyocyte differentiation, proliferation, and maturation across diverse genetic backgrounds of CHD. Ongoing studies on screening drugs that regulate cell cycling are poised to translate this nascent technology of enhancing cardiomyocyte proliferation into a new therapeutic paradigm for CHD surgical interventions.

The circle breathing system was unsafe for spontaneous breathing because of hypercapnia during anesthesia. Few studies have examined the minimizing dead space in breathing tubing. This study investigated one-way valves in the breathing tubing during spontaneous breathing in piglets. Six female piglets aged 68–71 days spontaneously breathed sevoflurane for 4 h randomly via traditional or anti-rebreathing tubing. Arterial carbon dioxide tension (PaCO₂) and respiratory characteristics were used to assess spontaneous breathing efficiency. mRNA-based methods, immunohistochemistry, and histology were used to assess the lungs. After induction, all piglets had mild hypercapnia. Those who breathed via traditional tubing experienced severe hypercapnia and required assisted ventilation (mean [95% confidence interval for mean]: 3 [0.5; 5.5] times) over 4 h. Piglets who breathed via anti-rebreathing tubing were able to normalize without assisted ventilation in less than 3 h and maintained. PaCO₂ was higher in the traditional group than the anti-rebreathing group at 3 and 4 hours (46.3 [42.1; 50.5] vs. 38.3 [34.1; 42.5] mmHg, p = 0.020; 46.3 [42.6; 50.0] vs. 40.7 [37.0; 44.4] mmHg, p = 0.040). However, one-way valves increased resistance to breathing. For the lungs, mRNA-based methods indicated higher expressions of cyclin-dependent kinase, cell division cycle 20, and cyclin B2 in the traditional group; immunohistochemistry identified higher expression of phosphorylated histone 2AX in the traditional group; histology showed similar damage between the groups. These findings suggest that one-way valves inside breathing tubing reduced dead space during spontaneous breathing and enhanced inhalation anesthesia advantages in the circle breathing system.

Activated phosphoinositide 3-kinase delta syndrome (APDS) is an autosomal dominant inborn errors of immunity resulting from gain of function mutations in the PIK3CD gene or loss of function mutations in the PIK3R1 gene. These mutations lead to hyperactivation of the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (mTOR) signaling pathways, causing complex deficiencies in cellular and humoral immunity. APDS patients exhibit diverse clinical manifestations including recurrent respiratory infections, nonneoplastic lymphoproliferation, an increasing risk of malignancy, and autoimmune diseases. Neurodevelopmental abnormalities, short stature, failure to thrive, and psychological disorders are also observed. Management strategies for APDS involve antibiotic prophylaxis and immunoglobulin replacement therapy, immunosuppressive therapies, and hematopoietic stem cell transplantation for severe cases. Targeted therapies, such as the mTOR inhibitor sirolimus and the elective Phosphoinositide 3-kinase delta inhibitor leniolisib, have emerged as promising options, demonstrating both safety and effectiveness. Continuous monitoring and further research are essential to optimize treatment strategies and understand the long-term implications of these interventions. This review aims to summarize the pathogenesis, clinical manifestations, and treatment of APDS.