X-linked hyper-IgM (X-HIGM), which results from mutations of the CD40 ligand gene (CD40LG) located on chromosome Xq26.3, is characterized by a defective T-B lymphocyte cross talk and class switch recombination (CSR). The present study aimed to evaluate the expression of CD40L and lymphocyte subsets using flow cytometry and to identify the novel genetic defect of CD40LG responsible for X-HIGM in a Chinese family. We reported an X-HIGM case caused by a novel mutation in CD40LG. The expression of CD40L was absent on the surface of activated CD4 + T cells evaluated using flow cytometry. The total number of mature B cells in circulation was normal, but memory B cells were significantly decreased. In helper T cells, Th2 was dominant, and the numbers of Th1 and Th17 were decreased. The results of genetic analysis revealed a new causative mutation in CD40L (NM_000074;exon5;c.505_506del), which leads to a change in amino acids (p.Y169Lfs*31) appearing in the proband. The frame shift mutation led to incorrect amino acid translation and loss of β-pleated sheet and loop region, which produced a mutant dysfunctional protein. This study provides a complete picture of X-HIGM and broadens our knowledge of the pathogenicity of the CD40L variant spectrum.

Background Hereditary cancers are the consequence of inherited genetic variants that increase the risk of cancer development. The susceptibility to hereditary cancers can be increased by a combination of variable genes with different penetrance, such as BRCA1/2, which are common genes involved in several types of familial cancers. The current study aims to analyze the genetic outcomes of genes linked to hereditary cancer, focusing on identifying pathogenic variants and their allele frequencies to improve risk assessment, genetic counseling, and targeted screening efforts in hereditary cancer management.

Method A group of 298 patients (278 females and 20 males) were chosen for the comprehensive hereditary cancer panel based on their clinical presentation, family history of cancer, and eligibility criteria for hereditary cancer testing. The panel included a custom target enrichment of 52 genes linked to an inherited predisposition to cancer. All therapeutically relevant observations were verified by Sanger sequencing.

Result Among the 298 individuals tested, 78.52 % tested negative for hereditary cancer-associated genes, while 21.48 % tested positive, with a higher proportion amongst females (89.06 %). A majority of those testing positive for hereditary cancer-associated pathogenic variants had a family history of cancer (71.88 %). Consanguinity was absent in most cases (81.90 %). Breast cancer was the most prevalent cancer (246 cases). Genes detected with L/LP variants include BRCA2, BRCA1, ATM, MSH2, MUTYH, and PALB2, with other genes detected at lower frequencies. Notably, BRCA1:c.1444_1447delATAA>A, p.(Ile482fs) variant occurred at the most high frequency (57 %).

Conclusion This study identified key pathogenic variants in hereditary cancer genes, with BRCA1 and BRCA2 mutations being the most prevalent. The findings reinforce the strong association between family history and hereditary cancer risk while indicating that consanguinity plays a limited role. This highlights the importance of comprehensive genetic screening and personalized counseling to improve hereditary cancer risk assessment and early detection strategies.

Objective This research was conducted at the Clinic for Children's Diseases of the University Clinical Hospital (SKB) Mostar. The aim of this study is to assess the frequency and reasons for performing karyotyping in neonatology practice over the past 15 years in the Herzegovina region.

Material and methods A retrospective epidemiological study was conducted covering a 15-year period from January 1, 2009, to December 31, 2023. The study included 150 newborns who underwent karyotype testing at the Intensive Care and Neonatology Department of the Clinic for Children's Diseases at University Clinical Hospital (SKB) Mostar.

Results Over the 15-year period, 48% (73/150) of the karyotypes were classified as normal, while 51% (77/150) were identified as pathological. The most common chromosomal abnormality was trisomy 21, which accounted for 70.13% (54/77) of the pathological cases. The results indicated that a majority of the fathers were older than 35 years (62.33%, or 48/77), whereas the age of the mothers was not statistically significant in this study. Additionally, 57% of multiparous women gave birth to children with chromosomal abnormalities. Premature newborns were more likely to have positive karyotype results.

Conclusion This research found no significant difference in the occurrence rates of pathological versus physiological karyotypes. Just over 50% of the children had confirmed karyotype deviations from normal variations. However, this suggests that healthcare resources may be misallocated in performing karyotyping, as the significance of the results may not always justify the testing.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are very rare dermatologic disorders characterized by extensive detachment of the epidermis. Although some drugs, infectious agents, HLA genes, malignancy and connective tissue diseases are thought to play a role in the development of the disease, the pathogenesis has not been fully elucidated. Type IV hypersensitivity reactions are thought to be the underlying cause of these diseases. Inflammatory changes such as purulent erosion, ulcers and crusting can be seen in the gastrointestinal system, urinary tract and genital mucosa. Some immunologic biyomarkers like as HLA-B* 1502, Granulysin and CCL-27 are used in clinical diagnosis, prognosis, treatment, and personalized new drug development that could further explain the pathogenesis of SJS and TEN. This review focuses on the pathophysiology of the SJS and TEN and presents it in light of current data on this subject. We recommend further in vivo and in vitro studies to unravel the underlying immunological mechanisms to determine appropriate intervention strategies.

Background In this study, the frequency of human platelet antigen (HPA) alleles and genotypes of platelet donors in Wuhan was evaluated and differences in HPA distribution between Wuhan and other regions in China were compared.

Study Design and Methods: HPA genotyping was performed using RT-qPCR in 1516 platelet donors in Wuhan. The allele frequencies of HPA-1 to −6, −10, −15, and −21 were calculated and evaluated according to the Hardy-Weinberg principle. Mismatch probability was calculated for each HPA system. The distribution and features of HPA systems in Wuhan were compared to those of other regions in China.

Results The observed allele frequencies and expected frequencies of HPA-1 to −6, −10, −15, and −21 showed no significant differences according to the Hardy-Weinberg principle (all P > 0.05). The prevalent allele among the nine HPA systems assessed in this study was allele “a”, except in the HPA-3 and HPA-15, where allele “b” was found in 43.3 % and 46.9 % of platelet donors, respectively. The highest transfusion mismatch probability was found in HPA-15 (37.40 %) and HPA-3 (37.05 %). Compared to other regions of China, Wuhan exhibits distinct characteristics in the distribution of HPA allele frequencies and genotypes among platelet donors.

Conclusion Distinct gene frequencies and genotypes were observed for HPA-1 to −6, −10, −15, and −21 among 1516 platelet donors from Wuhan compared with those of other regions. These results highlight the fact that HPA genotyping is of great significance for the establishment of HPA genotype registry and precise platelet transfusion in Wuhan.

Objective We investigated the distribution of polymorphisms in five hypertension-related drug-target genes including cytochrome P450 2C9*3 (CYP2C9 *3), angiotensin II receptor type 1(AGTR1) (1166 A>C), cytochrome P450 2D6 * 10 (CYP2D6 *10), β1-adrenergic receptors (ADRB1) (1165 G>C), and angiotensin converting enzyme (ACE I/D) in patients with hypertension in Beijing. The study aimed to provide a theoretical basis that will guide the application of personalized hypertensive therapy in this population and develop more targeted prevention and treatment strategies for hypertension and other chronic disease in different regions.

Materials and Methods We retrospectively analyzed 317 patients with hypertension from Beijing who were admitted to Peking University People’s Hospital from October 2021 to January 2024. The polymorphisms of five genes associated with Class A and B antihypertensive drugs were detected through real-time fluorescence PCR. In addition, we explored the distribution of different genotypes in the patient population while considering gender and comorbidities.

Results We obtained a significant difference in ADRB1(1165 G>C) between males and females, and the allele mutation frequency of ACE I/D was found to be higher in the Beijing population.

Conclusion Most hypertensive patients in the Beijing region carry a high frequency of CYP2D6 * 10, ADRB1(1165 G>C), and ACE I/D genes, implying that they might be more sensitive to β-blockers, potentially benefitting more from ACEI drugs. The high allele frequencies of CYP2D6 * 10, ADRB1(1165 G>C), and ACE I/D in Beijing hypertensive patients indicate enhanced sensitivity to β-blockers and good therapeutic response to ACE inhibitors. Therefore, clinicians need to account for these factors when prescribing the aforementioned medications.

Post-Traumatic Stress Disorder (PTSD) represents a significant mental health challenge closely associated with the consequences of traumatic experiences. Recently, small extracellular vesicles (sEVs) have been recognized as vital elements in the facilitation of intercellular communication. This review delves into the potential roles and mechanisms of sEVs in PTSD, concentrating on their involvement in neural signaling, immune system reactions, and the modulation of molecular biomarkers related to psychological disorders. By integrating recent research outcomes, this article aims to provide fresh insights into the pathophysiological aspects of PTSD and investigate prospective therapeutic approaches, underlining the significance of sEVs within the broader context of stress-related conditions.

Background It is a challenge for clinicians to choose the optimal third generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs) treatment for individual patients. In this meta-analysis we compare the efficacy of five third-generation EGFR-TKIs, as first-line and second-line therapies for non-small cell lung cancer (NSCLC) patients, and their adverse events (AEs).

Methods A Bayesian hierarchical network meta-analysis was conducted to evaluate the hazard ratios (HR) of first-line therapeutic effects and AEs for these third-generation EGFR-TKIs comparing with first-generation EGFR-TKIs. Additionally, a simple comparison analysis was conducted to evaluate second-line therapeutic effects.

Results All third-generation TKIs exhibited superior efficacy compared to Gefitinib in first-line treatment. Furmonertinib achieved the lowest HR in the exon 19 deletions subgroup (HR: 0.35; 95 % CI: 0.23-0.54), while Lazertinib showed the most favorable HR in the exon 21 L858R subgroup (HR: 0.44; 95 % CI: 0.28-0.70) and among patients with brain metastases (HR: 0.33; 95 % CI 0.18-0.59). In the second-line setting, Furmonertinib achieved the highest numerically objective response rate across the overall population (74.0 %; 95 % CI: 68.0-80.0 %) and all evaluated subgroups. Adverse event analysis showed that Furmonertinib had the lowest overall AE incidence, and Lazertinib had the lowest rate of high-grade (≥ grade 3) AEs.

Conclusions All third-generation EGFR-TKIs exhibited favorable efficacy in both first- and second-line settings. Differences in AE profiles were also noted.

Background Previous studies have suggested a potential link between the gut microbiota and diverticulitis. However, the causal relationships as well as underlying mechanisms remain unclear.

Methods The causal effects of gut microbiota on diverticulosis & diverticulitis was assessed using two-sample Mendelian randomization analysis. The sensitivity analyses were also performed. We then used integrative bioinformatics tools to identify core genes associated with diverticulitis and explore their potential mechanisms and therapeutic targets.

Results Inverse variance weighted analysis indicated that Family XIII (OR=0.281, 95 % CI: 0.093-0.853, P = 0.025) and Defluviitaleaceae UCG-011 (OR=0.382, 95 % CI: 0.162-0.898, P = 0.027) were negatively associated with the risk of diverticulosis and diverticulitis, whereas Oscillospira (OR=3.514, 95 % CI: 1.146-10.779, P = 0.028), Ruminiclostridium 6 (OR=2.629, 95 % CI: 1.093-6.322, P = 0.031), Lachnoclostridium (OR=2.458, 95 % CI: 1.014-5.962, P = 0.047), and Desulfovibrionales (OR=2.157, 95 % CI: 1.038-4.480, P = 0.039) were positively associated with disease risk. The sensitivity analyses validated these correlations. Through SNP annotation, we identified 23 host genes associated with pathogenic gut microflora in diverticulosis and diverticulitis, and retrieved 213 diverticulitis-related genes from GeneCards. Intersection analysis revealed LRRC4C as the sole shared gene. Differential expression analysis further showed that LRRC4C was significantly downregulated in diverticulitis compared to infective colitis. Finally, eight candidate drugs were identified as potential inducers of LRRC4C expression.

Conclusion The research revealed potential causal relationships between gut microbiota and diverticulitis. LRRC4C was identified as a core gene associated with pathogenic microbial traits in diverticulitis, and candidate therapeutic drugs for diverticulitis based on LRRC4C were predicted, offering novel strategies for the prevention and management of the disease.

We report on a rare 110 kilobase contiguous gene deletion within chromosome region Xq28, encompassing 7 annotated Online Mendelian Inheritance in Man (OMIM) genes and extending from BCAP31 to the telomeric-located PDZD4. We review 13 other reported contiguous deletions in this region and analyze their clinical phenotypes. The novel findings in our case were orofacial clefting and a vascular ring. The major clinical anomalies in our case appear to be due to the combined effects of BCAP31, SRPK3 and SSR4 deletions. This combination produces a severe neonatal disorder whose features further refine our knowledge about deletions within Xq28. Additionally, the observation of multiple nonrecurring breakpoints among the published cases suggests that the deletions occur by random chromosome breakage.