Background HBV is closely associated with the incidence of B-NHL (B-cell non-hodgkin lymphoma). This project intends to establish HBV infection-induced B-NHL cells and animal models to clarify the mutual mechanism of HBV infection and B-NHL pathogenesis.

Methods The relationship between HBV and B-NHL was studied based on the HBV infection model, which included CTC cells and HBV transgenic mice. Moreover, differential expression analysis of transcriptome profiling was performed to confirm the mechanism.

Results The HBsAg expression and HBV-DNA could be found in tumor tissues of HBV group, but negative in the control group. Moreover, there were clearly differences between the two groups in the transcriptome of tumor tissues and CTC. HBsAg significantly promoted lymphocytes associated with c-Myc and PD-L1.

Conclusion The promoted effect induced by HBsAg in lymphocytes was associated with PD-L1 mediated by c-Myc.

Circular RNAs (circRNAs) are a newly discovered class of endogenous non-coding RNAs with a closed-loop structures, and they exert crucial regulatory functions in diverse biological processes and disease development through the modulation of linear RNA transcription, downstream gene expression, and protein translation, among others. Circular RNA FOXO3(circFOXO3, Hsa_circ_0006404) originates from exon 2 of the FOXO3 gene and exhibits widespread cytoplasmic expression in eukaryotic cells. It shows specific expression in different tissues or cells. Recent research has associated circFOXO3 with various diseases such as cancer, cardiovascular diseases, neurological disorders, senescence, and inflammation. However, a comprehensive review of the research progress of circFOXO3 in human diseases has not been conducted. In this paper, we provide a systematic review of the latest advances in circFOXO3 research in diseases, elucidate its biological functions and potential molecular mechanisms, and discuss the future directions and challenges in circRNAs research to provide valuable references and inspiration for research in this field.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with a heterogeneous group of symptoms, including characteristic cafe-au-lait macules, axillary or inguinal freckling, Lisch nodules, as well as skeletal deformation, scoliosis, mental retardation, and tumors of the nervous system. Klinefelter syndrome (KS) is a gonadal dysgenesis, with symptoms in males, including an extra X chromosome, leading to tall stature, hypogonadism, and infertility. Although the co-occurrence of NF1 and KS is a rare finding, this report describes this unique entity detected in an eight-year-old boy with numerous hyperpigmentation spots, a multitude of skin and subcutaneous nodules, seizures, arterial stenosis, and mild gynecomastia. Whole-exome sequencing (WES) was conducted along with copy number analysis for the proband and his parents. Multiplex Ligation-dependent Probe Amplification (MLPA) is used to validate the copy number variations detected by next-generation sequencing (NGS). The results showed a pathogenic heterozygous mutation (c.246_247del, p.Gln83Valfs*23) in a human neurofibromin 1 gene (NF1), detected in the proband and his father, whilst the genetic analysis performed by the karyotype revealed a copy gain of the X chromosome (47, XXY) leading to KS. This rare occurrence of NF1 with co-occurrence of KS may raise some concerns and difficulties in the clinical management of this case, particularly Testosterone hormone replacement therapy and the potential risks of malignancies. Therefore, clinicians may ask for KS genetic tests in male patients with NF1 who have symptoms of gynaecomasia or infertility, and closely monitor for potential malignancies and other complications. Compellingly, this case emphasizes the importance of advanced genetic analysis in providing genetic tools for diagnosing and managing individuals with rare and complex syndromes with overlapping clinical features. Early detection and comprehensive clinical interventions are the key cornerstones to improving patient outcomes.

Identifying the circadian clock first provided the genetic basis for behaviour, and our understanding of circadian rhythms has since expanded to provide molecular insight into disease and physiology. The synchronization of central and peripheral clocks and robust daily rhythms can be achieved in a wide range of physiological systems and homeostatic responses can be supplemented. The rhythmical epigenome, which works as a central regulator, determines the circadian transcription of cell types. The rhythmical epigenome imposes oscillation on biological systems that momentarily split metabolism within 24 h. Interactions between the endogenous circadian system govern blood pressure, sleep, obesity and postural variations. Human health is dependent on the circadian rhythm. It can depict disease dynamics as well as overall drug efficacy monitoring to optimize the therapy effect. Circadian rhythms can collectively drive various metabolic activities, but dietary habits, sleep patterns, and other factors can also influence the circadian rhythm. The synergy of circadian rhythm and metabolism can bring new insights and personalized analysis for disease development causes and prevention. The understanding of the molecular clock and disease relationship can be exploited to determine treatment timing as well as new therapy targets.

Background Nephrotic syndrome (NS) is a renal disease characterized by excessive proteinuria (greater than 3.5 g/dl per 24 h), which results in hypoalbuminemia and leads to hyperlipidemia, edema, and various complications. NS patients typically respond to standard steroid treatment (prednisolone) and are classified as having steroid-sensitive nephrotic syndrome (SSNS). However, patients who do not respond to steroid therapy after 4 weeks are referred to as having steroid- resistant nephrotic syndrome (SRNS). The unequal response to steroid treatment in nephrotic syn-drome involved many factors, including genetic, medication, and kidney diseases. The CYP3A gene family is predominantly involved in the metabolism of medications used in the treatment of NS.

Methodology A systematic literature review was conducted from January 2014 to June 2024 using an extensive electronic search of data related to pediatric nephrotic syndrome and the CYP gene family, including associated polymorphisms. Through this review, we systematically ana-lyze factors that affect the metabolism of medications targeting the CYP3A gene family (including steroidal and non-steroidal drugs) commonly used in the treatment of NS and its comorbidities. Conclusion: Studies have correlated the relationship between polymorphisms in the CYP3A gene family and medication in NS, with 90 % of the research focusing primarily on post-kidney transplant NS patients. Many studies have reported a correlation between CYP3A gene family polymorphisms and increased tacrolimus (TAC) dosage.

Introduction Poretti-Boltshauser Syndrome (PBS) is a rare neuro-ophthalmological disorder with autosomal recessive inheritance. It is characterized by non-progressive cerebellar ataxia, delay in neuropsychomotor development, intellectual disability, and vision abnormalities. PBS is caused by mutations in the LAMA1 gene, resulting in cerebellar abnormalities, including cerebellar cysts in most cases.

Case presentation We present two siblings with LAMA1 mutations and distinct phenotypic presentation, with one of them showing no evidence of cerebellar cysts on magnetic resonance imaging (MRI).

Conclusion This study highlights intrafamilial variability in patients with Poretti-Boltshauser Syndrome (PBS). Patient 1 exhibits more pronounced cerebellar dysplasia (with cysts) and oculomotor apraxia, while Patient 2 shows milder cerebellar dysplasia (without cysts) and a macular hole. These findings underscore the importance of comprehensive evaluation and genetic testing for accurate diagnosis and management of PBS.

Background The genic etiology of sudden sensorineural hearing loss (SSNHL) is associated with gene polymorphism which is related to oxygen metabolism of cochlear hair cells.

Objective To investigate the genetic susceptibility of SOD2 gene polymorphism in sudden sensorineural hearing loss (SSNHL).

Method The genotype of three tag SNPs (rs5746136, rs2842960, rs4880) variants were detected among 148 patients with SSNHL in Yunnan Province, China, and 171 matched participants without hearing loss in control group were used to screen for any risk-associated SNPs.

Result The A/G genotype at rs5746136 locus (OR=1.811, 95 % CI=1.161-2.826, p = 0.009) was associated with susceptibility to SSNHL in Yunnan Province.

Conclusion SOD2 gene with the rs5746136 A/G genotype is associated with an increased risk of sudden sensorineural hearing loss (SSNHL), whereas the other two tag SNPs, rs2842960 and rs4880, show no significant correlation with SSNHL. Specifically, the tag SNP rs5746136 A/G appears to be a susceptibility gene for SSNHL.

RNA-binding proteins (RBPs) are integral components of cellular machinery, playing crucial roles in the regulation of gene expression and maintaining genetic stability. Their interactions with RNA molecules govern critical processes such as mRNA splicing, stability, localization, and translation, which are essential for proper cellular function. These proteins interact with RNA molecules and other proteins to form ribonucleoprotein complexes (RNPs), hence controlling the fate of target RNAs. The interaction occurs via RNA recognition motif, the zinc finger domain, the KH domain and the double stranded RNA binding motif (all known as RNA-binding domains (RBDs). These domains are found within the coding sequences (intron and exon domains), 5’ untranslated regions (5’UTR) and 3’ untranslated regions (3’UTR). Dysregulation of RBPs can lead to genomic instability, contributing to various pathologies, including cancer neurodegenerative diseases, and metabolic disorders. This study comprehensively explores the multifaceted roles of RBPs in genetic stability, highlighting their involvement in maintaining genomic integrity through modulation of RNA processing and their implications in cellular signalling pathways. Furthermore, it discusses how aberrant RBP function can precipitate genetic instability and disease progression, emphasizing the therapeutic potential of targeting RBPs in restoring cellular homeostasis. Through an analysis of current literature, this study aims to delineate the critical role of RBPs in ensuring genetic stability and their promise as targets for innovative therapeutic strategies.

Background Polydactyly and syndactyly, which are commonly encountered congenital limb deformities, rarely occur together and are linked with significant genetic mutations. This report sheds light on a unique co-presentation involving mutations in both the GLI3 and TBX5 genes, offering a deeper understanding of the genetic interactions that may influence limb development. This case report is important to increase our knowledge on genetic bases of limb malformations.

Case presentation We report the case of an 8-month-old boy, born to non-consanguineous parents, presenting with both polydactyly and syndactyly in his limbs, in particular, complete syndactyly between the third to fifth fingers and post-axial polydactyly of the feet. His father showed a similar phenotype. Genetic testing identified a pathogenic heterozygous variant in the GLI3 gene (c.3762 T > A, p.(Tyr1254 *)) and a variant of uncertain significance in the TBX5 gene (c.1063 C>T, p.(Arg355Cys)).

Conclusions This case highlights the complex nature of diagnosing and managing congenital limb deformities driven by genetic factors. It underscores the critical importance of comprehensive genetic testing in determining the etiology of limb malformations. The GLI3 variant, classified according to ACMG guidelines as a class IV mutation, likely results in a truncated protein due to a premature stop codon, confirmed by family segregation analysis indicating its paternal origin, suggesting autosomal dominant inheritance. Notably, the TBX5 gene variant, often associated with Holt-Oram syndrome—which is characterized by only hand skeletal anomalies and early-onset atrial fibrillation—suggests a risk of developing cardiac issues that are not currently present but may emerge as the child grows. This potential for evolving clinical manifestations necessitates vigilant long-term monitoring and may influence future medical management and therapeutic approaches.

Background Limb-Girdle Muscular Dystrophy (LGMD) is a rare heterogeneous group of neuromuscular disorders distinguished by progressive weakness of limb-girdle muscles. Diagnosis of LGMD is a challenging task and requires multiple obligatory assays.

Objective To study the epidemiology, clinical features, the genetic variability in patients diagnosed with LGMD through Next Generation Sequencing.

Material and Method A retrospective study of 27 patients suspected of LGMD was done to study the phenotypic presentation and the genotypic alteration of the patients, presenting to a tertiary care center in Rajasthan were studied.

Results Out of the twenty-seven patients suspected of LGMD, nineteen patients took genetic tests, while eight patients underwent biopsy. Among the nineteen patients, seventeen patients were identified with pathogenic mutations. Autosomal Recessive (LGMD-R) was the most common subgroup in this cohort. In the LGMD R1 subgroup, the most common mutation was c.2051-1 G>T and the exon hotspot was 18-22. The deleterious mutations in the LGMD R2 subgroup were distributed along the entire coding sequence, without any hotspot. However, C2E, C2F, and DysF domains contain variants at higher frequencies. The types of mutations were mostly point mutations (34 % of missense mutations and 66 % of nonsense mutations). We identified one novel mutation which was considered as a stop codon. Patients(n = 8) who underwent muscle biopsy for immunohistochemistry, had absent/reduced sarcoglycan uptake (n = 4) or absent dysferlin (n = 2) on the sarcolemma, while the remaining two biopsies were inconclusive (due to multiple protein deficiencies).