Genetic variation features of neonatal hyperbilirubinemia caused by inherited diseases

BACKGROUND Genetic factors play an important role in neonatal hyperbilirubinemia(NH)caused by genetic diseases.AIM To explore the characteristics of genetic mutations associated with NH and analyze the correlation with genetic diseases.METHODS This was a retrospective cohort study.One hundred and five newborn patients diagnosed with NH caused by genetic diseases were enrolled in this study between September 2020 and June 2023 at the Second Affiliated Hospital of Xiamen Medical College.A 24-gene panel was used for gene sequencing to analyze gene mutations in patients.The data were analyzed via Statistical Package for the Social Sciences 20.0 software.RESULTS Seventeen frequently mutated genes were found in the 105 patients.Uridine 5'-diphospho-glucuronosyltransferase 1A1(UGT1A1)variants were identified among the 68 cases of neonatal Gilbert syndrome.In patients with sodium taurocholate cotransporting polypeptide deficiency,the primary mutation identified was Na+/taurocholate cotransporting polypeptide Ntcp(SLC10A1).Adenosine triphosphatase 7B(ATP7B)mutations primarily occur in patients with hepatolenticular degeneration(Wilson's disease).In addition,we found that UGT1A1 and glucose-6-phosphate dehydrogenase mutations were more common in the high-risk group than in the low-risk group,whereas mutations in SLC10A1,ATP7B,and heterozygous 851del4 mutation were more common in the low-risk group.CONCLUSION Genetic mutations are associated with NH and significantly increase the risk of disease in affected newborns.

Genetic Variations and Nonalcoholic Fatty Liver Disease:Field Synopsis,Systematic Meta-Analysis,and Epidemiological Evidence

Objective To systematically summarize the published literature on the genetic variants associated with nonalcoholic fatty liver disease(NAFLD).Methods Literature from Web of Science,PubMed,and Embase between January 1980 and September 2022 was systematically searched.Meta-analyses of the genetic variants were conducted using at least five data sources.The epidemiologic credibility of the significant associations was graded using the Venice criteria.Results Based on literature screening,399 eligible studies were included,comprising 381 candidate gene association,16 genome-wide association,and 2 whole-exome sequencing studies.We identified 465 genetic variants in 173 genes in candidate gene association studies,and 25 genetic variants in 17 genes were included in the meta-analysis.The meta-analysis identified 11 variants in 10 genes that were significantly associated with NAFLD,with cumulative epidemiological evidence of an association graded as strong for two variants in two genes(HFE,TNF),moderate for four variants in three genes(TM6SF2,GCKR,and ADIPOQ),and weak for five variants in five genes(MBOAT7,PEMT,PNPLA3,LEPR,and MTHFR).Conclusion This study identified six variants in five genes that had moderate to strong evidence of an association with NAFLD,which may help understand the genetic architecture of NAFLD risk.

Epidemiological Surveillance: Genetic Diversity of Rotavirus Group A in the Pearl River Delta, Guangdong, China in 2019

Objective This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A(RVA)in the Pearl River Delta region of Guangdong Province,China.Methods This study included individuals aged 28 days–85 years.A total of 706 stool samples from patients with acute gastroenteritis collected between January 2019 and January 2020 were analyzed for 17 causative pathogens,including RVA,using a Gastrointestinal Pathogen Panel,followed by genotyping,virus isolation,and complete sequencing to assess the genetic diversity of RVA.Results The overall RVA infection rate was 14.59%(103/706),with an irregular epidemiological pattern.The proportion of co-infection with RVA and other pathogens was 39.81%(41/103).Acute gastroenteritis is highly prevalent in young children aged 0–1 year,and RVA is the key pathogen circulating in patients 6–10 months of age with diarrhea.G9P[8](58.25%,60/103)was found to be the predominant genotype in the RVA strains,and the 41 RVA-positive strains that were successfully sequenced belonged to three different RVA genotypes in the phylogenetic analysis.Recombination analysis showed that gene reassortment events,selection pressure,codon usage bias,gene polymorphism,and post-translational modifications(PTMs)occurred in the G9P[8]and G3P[8]strains.Conclusion This study provides molecular evidence of RVA prevalence in the Pearl River Delta region of China,further enriching the existing information on its genetics and evolutionary characteristics and suggesting the emergence of genetic diversity.Strengthening the surveillance of genotypic changes and gene reassortment in RVA strains is essential for further research and a better understanding of strain variations for further vaccine development.

Age-specific heterogeneity of genetic susceptibility to cardiovascular disease might have opposite outcomes depending on the presence of prediabetes

Examining age-specific heterogeneity of susceptibility to cardiovascular disease is also essential in individuals without prediabetes to determine its relative size and direction compared to those with prediabetes.Of particular interest,age-specific heterogeneity in genetic susceptibility may exhibit opposite directions depending on the presence or absence of prediabetes.

The critical importance of epigenetics in autoimmune-related skin diseases

Autoimmune-related skin diseases are a group of disorders with diverse etiology and pathophysiology involved in autoimmunity.Genetics and environmental factors may contribute to the development of these autoimmune disorders.Although the etiology and pathogenesis of these disorders are poorly understood,environmental variables that induce aberrant epigenetic regulations may provide some insights.Epigenetics is the study of heritable mechanisms that regulate gene expression without changing DNA sequences.The most important epigenetic mechanisms are DNA methylation,histone modification,and noncoding RNAs.In this review,we discuss the most recent findings regarding the function of epigenetic mechanisms in autoimmune-related skin disorders,including systemic lupus erythematosus,bullous skin diseases,psoriasis,and systemic sclerosis.These findings will expand our understanding and highlight the possible clinical applications of precision epigenetics approaches.

Interaction between diet and genetics in patients with inflammatory bowel disease

In this editorial,we comment on the article by Marangoni et al,published in the recent issue of the World Journal of Gastroenterology 2023;29:5618-5629,about“Diet as an epigenetic factor in inflammatory bowel disease”.The authors emphasized the role of diet,especially the interaction with genetics,in promoting the inflam-matory process in inflammatory bowel disease(IBD)patients,focusing on DNA methylation,histone modifications,and the influence of microRNAs.In this editorial,we explore the interaction between genetics,gut microbiota,and diet,in an only way.Furthermore,we provided dietary recommendations for patients with IBD.The Western diet,characterized by a low fiber content and deficiency the micronutrients,impacts short-chain fatty acids production and may be related to the pathogenesis of IBD.On the other hand,the consumption of the Mediter-ranean diet and dietary fibers are associated with reduced risk of IBD flares,particularly in Crohn’s disease(CD)patients.According to the dietary guidance from the International Organization for the Study of Inflammatory Bowel Diseases(IOIBD),the regular consumption of fruits and vegetables while reducing the consumption of saturated,trans,dairy fat,additives,processed foods rich in maltodextrins,and artificial sweeteners containing sucralose or saccharine is recommended to CD patients.For patients with ulcerative colitis,the IOIBD recommends the increased intake of natural sources of omega-3 fatty acids and follows the same restrictive recommendations aimed at CD patients,with the possible inclusion of red meats.In conclusion,IBD is a complex and hetero-geneous disease,and future studies are needed to elucidate the influence of epigenetics on diet and microbiota in IBD patients.

Genetic risk stratification of inflammatory bowel disease-associated venous thromboembolism:An Asian perspective

The utilisation of polygenic scoring models may enhance the clinician’s ability to risk stratify an inflammatory bowel disease patient’s individual risk for venous thromboembolism(VTE)and guide the appropriate usage of VTE thromboprophylaxis,yet there is a need to validate such models in ethnically diverse populations.

Integration between Genomic and Computational Statistical Surveys for the Screening of SNP Genetic Variants in Inflammatory Bowel Disease (IBD) Pediatric Patients*

Inflammatory bowel diseases (IBD) are complex multifactorial disorders that include Crohn’s disease (CD) and ulcerative colitis (UC). Considering that IBD is a genetic and multifactorial disease, we screened for the distribution dynamism of IBD pathogenic genetic variants (single nucleotide polymorphisms;SNPs) and risk factors in four (4) IBD pediatric patients, by integrating both clinical exome sequencing and computational statistical approaches, aiming to categorize IBD patients in CD and UC phenotype. To this end, we first aligned genomic read sequences of these IBD patients to hg19 human genome by using bowtie 2 package. Next, we performed genetic variant calling analysis in terms of single nucleotide polymorphism (SNP) for genes covered by at least 20 read genomic sequences. Finally, we checked for biological and genomic functions of genes exhibiting statistically significant genetic variant (SNPs) by introducing Fitcon genomic parameter. Findings showed Fitcon parameter as normalizing IBD patient’s population variability, as well as inducing a relative good clustering between IBD patients in terms of CD and UC phenotypes. Genomic analysis revealed a random distribution of risk factors and as well pathogenic SNPs genetic variants in the four IBD patient’s genome, claiming to be involved in: i) Metabolic disorders, ii) Autoimmune deficiencies;iii) Crohn’s disease pathways. Integration of genomic and computational statistical analysis supported a relative genetic variability regarding IBD patient population by processing IBD pathogenic SNP genetic variants as opposite to IBD risk factor variants. Interestingly, findings clearly allowed categorizing IBD patients in CD and UC phenotypes by applying Fitcon parameter in selecting IBD pathogenic genetic variants. Considering as a whole, the study suggested the efficiency of integrating clinical exome sequencing and computational statistical tools as a right approach in discriminating IBD phenotypes as well as improving inflammatory bowel disease (IBD) molecular diagnostic process.

Applications and developments of gene therapy drug delivery systems for genetic diseases

Genetic diseases seriously threaten human health and have always been one of the refractory conditions facing humanity.Currently,gene therapy drugs such as siRNA,shRNA,antisense oligonucleotide,CRISPR/Cas9 system,plasmid DNA and miRNA have shown great potential in biomedical applications.To avoid the degradation of gene therapy drugs in the body and effectively deliver them to target tissues,cells and organelles,the development of excellent drug delivery vehicles is of utmost importance.Viral vectors are the most widely used delivery vehicles for gene therapy in vivo and in vitro due to their high transfection efficiency and stable transgene expression.With the development of nanotechnology,novel nanocarriers are gradually replacing viral vectors,emerging superior performance.This review mainly illuminates the current widely used gene therapy drugs,summarizes the viral vectors and non-viral vectors that deliver gene therapy drugs,and sums up the application of gene therapy to treat genetic diseases.Additionally,the challenges and opportunities of the field are discussed from the perspective of developing an effective nano-delivery system.

Identification of Crop Diseases Based on Improved Genetic Algorithm and Extreme Learning Machine

As an indispensable task in crop protection,the detection of crop diseases directly impacts the income of farmers.To address the problems of low crop-disease identification precision and detection abilities,a new method of detection is proposed based on improved genetic algorithm and extreme learning machine.Taking five different typical diseases with common crops as the objects,this method first preprocesses the images of crops and selects the optimal features for fusion.Then,it builds a model of crop disease identification for extreme learning machine,introduces the hill-climbing algorithm to improve the traditional genetic algorithm,optimizes the initial weights and thresholds of the machine,and acquires the approximately optimal solution.And finally,a data set of crop diseases is used for verification,demonstrating that,compared with several other common machine learning methods,this method can effectively improve the crop-disease identification precision and detection abilities and provide a basis for the identification of other crop diseases.

A summary about dendritic cells in skin diseases

Dendritic cellls (DCs) comprise an es se ntial component of the immune system, are crucial in the initiation of antigen s pecific immune responses. In this summary we focus on summarizing on the central role of DCs in skin diseases: Bullous dermatoses, Dermatitis, Psoriasis, Lichen Planus , Graft-versus-host disease, Connect Tissue Diseases, Virus Diseases, Fungi Diseases, HIV, Urticaria, Urticaria pigmentosa, Mastocytosis, Tumour, Sola r dermatoses. Moreover,in this summary we review the distribution and phenotype of DCs in human skin. Markers and phenotyps 's study have provided strong suppo rt for a concept in which DCs play an important role in the pothogenesis of som e skin diseases.

Insights into the genetic architecture of congenital heart disease from animal modeling

Congenital heart disease(CHD)is observed in up to 1%of live births and is one of the leading causes of mortality from birth defects.While hundreds of genes have been implicated in the genetic etiology of CHD,their role in CHD pathogenesis is still poorly understood.This is largely a reflection of the sporadic nature of CHD,as well as its variable expressivity and incomplete penetrance.We reviewed the monogenic causes and evidence for oligogenic etiology of CHD,as well as the role of de novo mutations,common variants,and genetic modifiers.For further mechanistic insight,we leveraged single-cell data across species to investigate the cellular expression characteristics of genes implicated in CHD in developing human and mouse embryonic hearts.Understanding the genetic etiology of CHD may enable the application of precision medicine and prenatal diagnosis,thereby facilitating early intervention to improve outcomes for patients with CHD.

Genetic Analysis of Variants of the MYH6 Gene Promoter in Congenital Atrial Septal Defects

Background:Atrial septal defect(ASD)is one of the common congenital heart diseases.The MYH6 gene has a critical role in cardiac development but the role of MYH6 promoter variants in patients with ASD has not been explored.Methods:In 613 subjects including 320 ASD patients,we investigated the MYH6 gene promoter variants and verified the effect on gene expression by using cellular functional experiments and bioinformatics analysis.Results:Eleven variants were identified in the MYH6 gene promoter,of which four variants were found only in ASD patients,and two variants(g.3434G>C and g.4524C>T)were identified for the first time.Cellular functional experiments indicated that all four variants reduced the transcriptional activity of the MYH6 gene promoter(p<0.05).Subsequent analysis through the JASPAR(A database of transcription factor binding profiles)suggests that these variants may alter transcription factor binding sites,which may in turn lead to changes in myocardin subunit expression and ASD formation.Conclusions:Our study for the first time focuses on variants in the promoter region of the MYH6 gene in Chinese patients with ASD and the discovered variants have functional significance.The study provides new insights in the role of the MYH6 gene promoter region to better understand the genetic basis of ASD formation and facilitates clinical diagnosis.

Androgens/Androgen Receptor in the Management of Skin Diseases

Beyond regulation of male sexual function, the increasing evidence shows that androgens and androgen receptor (AR) have a variety of physiological and pathological effects on the skin. Skin cells express all androgen metabolizing enzymes that are required for independent skin androgen synthesis and the development of hyperandrogenic related disorders such as acne, hirsutism and androgenetic alopecia. Targeting various elements of androgen function and metabolism is the major goal of medication design for the treatment of androgen-related diseases. Antiandrogen drugs such as clascoterone, flutamide could improve conditions. Even though the involvement of androgens and AR in skin diseases has been investigated for a long time, their molecular mechanisms in skin disorders remain largely insufficient. In this review, recent studies and advances on the role of androgens/AR in several skin-related diseases and their therapeutics are systematically summarized.

Editor's Choice——Application of genetic engineering for the treatment of neurodegenerative diseases

Gene therapy has been shown to be an effective method for protecting neural functions in the substantia nigra,

Advancing Neuropsychiatric Care through Genetic and Molecular Insights

Neuropsychiatric diseases, including ADHD, schizophrenia, and bipolar disorder, are increasingly prevalent but poorly understood at the molecular level. The complexities of diagnosing and treating these disorders emphasize the need for objective, quantitative data to improve diagnostic accuracy and treatment efficacy. This study aims to explore the genetic underpinnings of neuropsychiatric diseases, contrasting them with well-characterized diseases like breast cancer, and discuss the role of specific genetic mutations and their implications for personalized treatment. The paper delves into the genetic and molecular insights of neuropsychiatric diseases, examining the role of specific genetic mutations and the potential for gene editing technologies like CRISPR. It contrasts the genetic underpinnings of neuropsychiatric diseases with well-characterized diseases like breast cancer, highlighting the potential for a shift towards molecular and genetic-based diagnostics and treatments. The study argues that a shift towards molecular and genetic-based diagnostics and treatments could revolutionize our approach to neuropsychiatric diseases, much like how biomarker tests have transformed breast cancer treatment. It concludes by advocating for a more personalized approach to healthcare, tailored to an individual’s unique genetic makeup, as the future of neuropsychiatric disease diagnosis and treatment.

Propensity for Progressive Renal Disease in Nephroangiosclerosis: A Refractory Phenotype of Genetic Vasculopathy in Essential Hypertension

Background: Inadequate treatment of essential hypertension (EH), Obesity, smoking, carbohydrate intolerance, hyperlipidemia, and nephrotox-in-exposure are major confounding factors in progression of Nephroangiosclerosis (N). However, neither the prevalence nor the severity of EH is a reliable predictor of individuals at risk for subsequent nephropathy. Patients and Methods: A 10-years retrospective analysis of 165 adequately treated patients with EH. Results: We observed 2 different renal outcomes. Twenty-three (14%) patients manifested progressive renal disease with > doubling serum creatinine and proteinuria with 3 reaching end-stage kidney disease. At start, biopsy of those patients showed features of “benign” nephroangiosclerosis (N) ± secondary form of focal and segmental glomerulosclerosis (without immune deposits). On the other hand;142 with similar demographic characteristics, duration and severity of disease did not show significant renal disease on follow up. Conclusion: Induction of progressive N, in patients with EH, is compatible with phenotypic susceptibilities of genetic disorders.

Differences in clinical and genetic characteristics between early-and late-onset narcolepsy in a Han Chinese cohort

Early-and late-onset narcolepsy constitutes two distinct diagnostic subgroups.However,it is not clear whether symptomology and genetic risk factors differ between early-and late-onset narcoleptics.This study compared clinical data and single-nucleotide polymorphisms(SNPs)between early-and late-onset patients in a large cohort of 899 Han Chinese narcolepsy patients.Blood,cerebrospinal fluid,and clinical data were prospectively collected from patients,and patients were genotyped for 40 previously reported narcolepsy risk-conferring SNPs.Genetic risk scores(GRSs),associations of five different sets of SNPs(GRS1–GRS5)with early-and late-onset narcolepsy,were evaluated using logistic regression and receiver operating characteristic curves.Mean sleep latency was significantly shorter in early-onset cases than in late-onset cases.Symptom severity was greater among late-onset patients,with higher rates of sleep paralysis,hypnagogic hallucinations,health-related quality of life impairment,and concurrent presentation with four or more symptoms.Hypocretin levels did not differ significantly between early-and late-onset cases.Only rs3181077(CCR1/CCR3)and rs9274477(HLA-DQB1)were more prevalent among early-onset cases.Only GRS1(26 SNPs;OR=1.513,95%CI:0.893–2.585;P<0.05)and GRS5(6 SNPs;OR=1.893,95%CI:1.204–2.993;P<0.05)were associated with early-onset narcolepsy,with areas under the receiver operating characteristic curves of 0.731 and 0.732,respectively.Neither GRS1 nor GRS5 included SNPs in HLA regions.Our results indicate that symptomology and genetic risk factors differ between early-and late-onset narcolepsy.This protocol was approved by the Institutional Review Board(IRB)Panels on Medical Human Subjects at Peking University People’s Hospital,China(approval No.Yuanlunshenlinyi 86)in October 2011.

Deep Learning Based Automated Diagnosis of Skin Diseases Using Dermoscopy

Biomedical image analysis has been exploited considerably by recent technology involvements,carrying about a pattern shift towards‘automation’and‘error free diagnosis’classification methods with markedly improved accurate diagnosis productivity and cost effectiveness.This paper proposes an automated deep learning model to diagnose skin disease at an early stage by using Dermoscopy images.The proposed model has four convolutional layers,two maxpool layers,one fully connected layer and three dense layers.All the convolutional layers are using the kernel size of 3∗3 whereas the maxpool layer is using the kernel size of 2∗2.The dermoscopy images are taken from the HAM10000 dataset.The proposed model is compared with the three different models of ResNet that are ResNet18,ResNet50 and ResNet101.The models are simulated with 32 batch size and Adadelta optimizer.The proposed model has obtained the best accuracy value of 0.96 whereas the ResNet101 model has obtained 0.90,the ResNet50 has obtained 0.89 and the ResNet18 model has obtained value as 0.86.Therefore,features obtained from the proposed model are more capable for improving the classification performance of multiple skin disease classes.This model can be used for early diagnosis of skin disease and can also act as a second opinion tool for dermatologists.

Helicobacter pylori and inflammatory skin diseases

Throughout the history of mankind, infections have been the major cause of diseases. Over the last decades, not only the incidence of emerging infectious diseases have increased, but also tremendous strides have been made in understanding the biology of several pathogenic microorganisms. Helicobacter pylori(H. pylori) is a spiral-shaped, gram-negative bacterium, which infects over the half of the world's population. H. pylori has been implicated in the pathogenesis of a number of gastrointestinal disorders. However, new researches have demonstrated that H. pylori is also involved in the pathogenesis of various extragastric diseases. The difference in the clinical outcome of H. pylori infection may be explained, at least in part, by host response to the infection and H. pylori virulence factors. It is obvious that as developments in the research on H. pylori spring up, an understanding of the pathophysiology of H. pylori infection will continue to be identified. Here in this review, we summarize the current knowledge about H. pylori and its association with inflammatory skin diseases.