Progress in clinical diagnosis and treatment of colorectal cancer with rare genetic variants

Targeted therapy is crucial for advanced colorectal cancer(CRC) positive for genetic drivers. With advances in deep sequencing technology and new targeted drugs, existing standard molecular pathological detection systems and therapeutic strategies can no longer meet the requirements for careful management of patients with advanced CRC. Thus, rare genetic variations require diagnosis and targeted therapy in clinical practice. Rare gene mutations, amplifications, and rearrangements are usually associated with poor prognosis and poor response to conventional therapy. This review summarizes the clinical diagnosis and treatment of rare genetic variations, in genes including erb-b2 receptor tyrosine kinase 2(ERBB2), B-Raf proto-oncogene, serine/threonine kinase(BRAF), ALK receptor tyrosine kinase/ROS proto-oncogene 1, receptor tyrosine kinase(ALK/ROS1), neurotrophic receptor tyrosine kinases(NTRKs), ret proto-oncogene(RET), fibroblast growth factor receptor 2(FGFR2), and epidermal growth factor receptor(EGFR), to enhance understanding and identify more accurate personalized treatments for patients with rare genetic variations.

Health diagnosis of ultrahigh arch dam performance using heterogeneous spatial panel vector model

Currently,more than ten ultrahigh arch dams have been constructed or are being constructed in China.Safety control is essential to long-term operation of these dams.This study employed the flexibility coefficient and plastic complementary energy norm to assess the structural safety of arch dams.A comprehensive analysis was conducted,focusing on differences among conventional methods in characterizing the structural behavior of the Xiaowan arch dam in China.Subsequently,the spatiotemporal characteristics of the measured performance of the Xiaowan dam were explored,including periodicity,convergence,and time-effect characteristics.These findings revealed the governing mechanism of main factors.Furthermore,a heterogeneous spatial panel vector model was developed,considering both common factors and specific factors affecting the safety and performance of arch dams.This model aims to comprehensively illustrate spatial heterogeneity between the entire structure and local regions,introducing a specific effect quantity to characterize local deformation differences.Ultimately,the proposed model was applied to the Xiaowan arch dam,accurately quantifying the spatiotemporal heterogeneity of dam performance.Additionally,the spatiotemporal distri-bution characteristics of environmental load effects on different parts of the dam were reasonably interpreted.Validation of the model prediction enhances its credibility,leading to the formulation of health diagnosis criteria for future long-term operation of the Xiaowan dam.The findings not only enhance the predictive ability and timely control of ultrahigh arch dams'performance but also provide a crucial basis for assessing the effectiveness of engineering treatment measures.

Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

Utilizing bioinformatics for integrated analysis of multiple genes in the diagnosis and pathogenesis of metastatic pheochromocytoma and paraganglioma

Objective:The aim of the study was to investigate effective diagnostic molecular markers and the specific mechanisms of metastatic pheochromocytomas and paragangliomas(PPGLs).Methods:Data were collected from GEO datasets GSE67066 and GSE60458.The R software and various packages were utilized for the analysis of differentially expressed genes,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,receiver operating characteristic curve assessment,logistic model construction,and correlation analysis.The NetworkAnalyst tool was used to analyze gene-miRNA interactions and signaling networks.In addition,the TIMER database was used to estimate the immune scores.Results:A total of 203 and 499 differentially expressed genes were identified in GSE67066 and GSE60458,respectively.These genes are implicated in cytokine and cytokine receptor interactions,extracellular matrix–receptor interactions,and platelet activation signaling pathways.Notably,MAMLD1,UST,MATN2,LPL,TWIST1,SFRP4,FRMD6,RBM24,PRIMA1,LYPD1,KCND2,CAMK2N1,SPOCK3,and ALPK3 were identified as the key genes.Among them,MATN2 and TWIST1 were found to be coexpressed with epithelial-mesenchymal transition–linked markers,whereas KCND2 and LPL exhibited associations with immune checkpoint expression and immune cell infiltration.Eight miRNAs were identified as potential regulators of key gene expression,and it was noted that TWIST1 might be regulated by SUZ12.Notably,the area under the curve of the 4-gene model for distinguishing between malignant and benign groups was calculated to be 0.918.Conclusions:The combined gene and mRNA expression model enhances the diagnostic accuracy of assessing PPGL metastatic potential.These findings suggest that multiple genes may play a role in the metastasis of PPGLs through the epithelial-mesenchymal transition and may influence the immune microenvironment.

Usher syndrome:Genetic diagnosis and current therapeutic approaches

Usher Syndrome(USH)is the most common deaf-blind syndrome,affecting approximately 1 in 6000 people in the deaf population.This genetic condition is characterized by a combination of hearing loss(HL),retinitis pigmentosa,and,in some cases,vestibular areflexia.Among the subtypes of USH,USH type 1 is considered the most severe form,presenting profound bilateral congenital deafness,vestibular areflexia,and early onset RP.USH type 2 is the most common form,exhibiting congenital moderate to severe HL for low frequencies and severe to profound HL for high frequencies.Conversely,type 3 is the rarest,initially manifesting mild symptoms during childhood that become more prominent in the first decades of life.The dual impact of USH on both visual and auditory senses significantly impairs patients'quality of life,restricting their daily activities and interactions with society.To date,9 genes have been confirmed so far for USH:MYO7A,USH1C,CDH23,PCDH15,USH1G,USH2A,ADGRV1,WHRN and CLRN1.These genes are inherited in an autosomal recessive manner and encode proteins expressed in the inner ear and retina,leading to functional loss.Although non-genetic methods can assist in patient triage and disease extension evaluation,genetic and molecular tests play a pivotal role in providing genetic counseling,enabling appropriate gene therapy,and facilitating timely cochlear implantation(CI).The CRISPR/Cas9 system and viral-based gene replacement therapy have recently emerged as highly promising techniques for treating USH.Regarding drug therapy,PTC-124 and Nb54 have been identified as promising drug interventions for genetic HL in USH.Simultaneously,CI has proven to be critical in the restoration of hearing.This review aims to summarize the genetic and molecular diagnosis of USH and highlight the importance of early diagnosis in Cuzzuol BR et al.Diagnosis and current treatments of USH WJO https://www.wjgnet.com 2 January 19,2024 Volume 11 Issue 1 guiding appropriate treatment strategies and improving patient prognosis.

Presymptomatic Diagnosis and Gene Therapy for Alzheimer’s Disease: Genomic, Therapeutic, and Ethical Aspects—A Systematic Review

Over the past three decades, genomic and epigenetic sciences have identified more than 70 genes involved in the molecular pathophysiology of Alzheimer’s disease (AD). DNA methylation, abnormal histone and chromatin regulation and the action of various miRNAs induce AD. The identification of mutated genes has paved the way for the development of diagnostic kits and the initiation of gene therapy trials. However, despite major advances in neuroscience research, there is yet no suitable treatment for AD. Therefore, the early diagnosis of this neurodegenerative disease raises several ethical questions, including the balance between the principle of non-maleficence and the principle of beneficence. The aims of this research were to present the genomic and ethical aspects of AD, and to highlight the ethical principles involved in its presymptomatic diagnosis and therapy. A systematic review of the literature in PubMed, Google Scholar and Science Direct was carried out to outline the genomic aspects and ethical principles relating not only to the presymptomatic diagnosis of AD, but also to its gene therapy. A total of 16 publications were selected. AD is a multifactorial disease that can be genetically classified into Sporadic Alzheimer’s Disease and Familial Alzheimer’s Disease based on family history. Gene therapy targeting specific disease-causing genes is a promising therapeutic strategy. Advancements in artificial intelligence applications may enable the prediction of AD onset several years in advance. While early diagnosis of AD may empower patients with full decision competence for early decision-making, it also carries implications for the patient’s family members, who are at risk of developing the disease, potentially becoming a source of confusion or anxiety. AD has a significant impact on the life of individuals at risk and their families. Given the absence of disease modifying therapy, genetic screening and early diagnosis for this condition raise ethical issues that must be carefully considered in the context of fundamental bioethical principles, including autonomy, beneficence, non-maleficence, and justice.

Value of procalcitonin and presepsin in the diagnosis and severity stratification of sepsis and septic shock

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.[1,2]Septic shock,the most severe form of sepsis,is characterized by circulatory and cellular/metabolic abnormalities,and can increase mortality to>40%.[1-3]Early recognition and risk stratification of septic shock are crucial but challenging because of the heterogeneity of its presentation and progression.

A review of the literature on the use of CRISPR/Cas9 gene therapy to treat hepatocellular carcinoma

Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emergence of therapeutic resistance in HCC patients,dlinicians have faced difficulties in treating such tumor.In addition,CRISPR/Cas9 screens were used to identify genes that improve the dlinical response of HCC patients.It is the objective of this article to summarize the current understanding of the use of the CRISPR/Cas9 system for the treatment of cancer,with a particular emphasis on HCC as part of the current state of knowledge.Thus,in order to locate recent developments in oncology research,we examined both the Scopus database and the PubMed database.The ability to selectively interfere with gene expression in combinatorial CRISPR/Cas9 screening can lead to the discovery of new effective HCC treatment regimens by combining clinically approved drugs.Drug resistance can be overcome with the help of the CRISPR/Cas9 system.HCC signature genes and resistance to treatment have been uncovered by genome-scale CRISPR activation screening although this method is not without limitations.It has been extensively examined whether CRISPR can be used as a tool for disease research and gene therapy.CRISPR and its applications to tumor research,particularly in HCC,are examined in this study through a review of the literature.

Wilm′s tumor gene1肽疫苗Galinpepimut-S在肿瘤免疫治疗中的应用

目的为Wilm′s tumor gene1(WT1)肽疫苗Galinpepimut-S(GPS)用于肿瘤免疫治疗的后续研究提供参考。方法采用计算机检索中国知网、PubMed等数据库自建库起至2022年12月的肿瘤免疫治疗相关文献,总结GPS在肿瘤免疫治疗中的应用现状。结果GPS能激发自身免疫系统,对WT1抗原产生强烈免疫反应而发挥抗肿瘤作用,在卵巢癌、恶性胸膜间皮瘤、急性髓系白血病、多发性骨髓瘤的治疗中均显示出较好的疗效。结论以GPS为代表的肿瘤疫苗是未来肿瘤治疗的重要方向,需进一步进行临床研究,以获取更多数据。

Circular RNAs in breast cancer diagnosis,treatment and prognosis

Breast cancer has surpassed lung cancer to become the most common malignancy worldwide.The incidence rate and mortality rate of breast cancer continue to rise,which leads to a great burden on public health.Circular RNAs(circRNAs),a new class of noncoding RNAs(ncRNAs),have been recognized as important oncogenes or suppressors in regulating cancer initiation and progression.In breast cancer,circRNAs have significant roles in tumorigenesis,recurrence and multidrug resistance that are mediated by various mechanisms.Therefore,circRNAs may serve as promising targets of therapeutic strategies for breast cancer management.This study reviews the most recent studies about the biosynthesis and characteristics of circRNAs in diagnosis,treatment and prognosis evaluation,as well as the value of circRNAs in clinical applications as biomarkers or therapeutic targets in breast cancer.Understanding the mechanisms by which circRNAs function could help transform basic research into clinical applications and facilitate the development of novel circRNA-based therapeutic strategies for breast cancer treatment.

AMME chromosomal region gene 1基因变异矮小相关综合征一例及文献复习

目的探讨1例身材矮小、面中部发育不全患儿的病因,以提高临床医师对特殊矮小综合征的认识。方法收集1例身材矮小、面中部发育不全患儿的临床资料,对患儿及父母行基因检测,并给予患儿常规治疗、随访。结果结合患儿特殊面容及基因检测,诊断为AMMECR1基因变异矮小相关综合征,结合文献复习总结AMMECR1基因变异矮小相关综合征特点。结论AMMECR1基因变异矮小相关综合征是一种罕见的X连锁遗传性疾病,临床主要表现为身材矮小、运动语言落后、肌张力减低、听力损失、面中部发育不全,部分存在心脏改变、腭裂、骨骼改变及椭圆形红细胞增多症、智力落后和肾钙质沉着症。该文报道1例AMMECR1基因新变异引起身材矮小、面中部发育不全患儿的病例资料,结合特殊面容及基因检测,诊断为AMMECR1基因变异矮小相关综合征。AMMECR1基因变异矮小相关综合征是一种罕见的X连锁遗传性疾病,本文初步概括其特点,并结合文献进行分析,以提高临床医师对AMMECR1基因变异矮小相关综合征的诊治。

Marker Ki-67 is a potential biomarker for the diagnosis and prognosis of prostate cancer based on two cohorts

BACKGROUND Prostate cancer(PCa)is a widespread malignancy,predominantly affecting elderly males,and current methods for diagnosis and treatment of this disease continue to fall short.The marker Ki-67(MKI67)has been previously demonstrated to correlate with the proliferation and metastasis of various cancer cells,including those of PCa.Hence,verifying the association between MKI67 and the diagnosis and prognosis of PCa,using bioinformatics databases and clinical data analysis,carries significant clinical implications.AIM To explore the diagnostic and prognostic efficacy of antigens identified by MKI67 expression in PCa.METHODS For cohort 1,the efficacy of MKI67 diagnosis was evaluated using data from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases.For cohort 2,the diagnostic and prognostic power of MKI67 expression was further validated using data from 271 patients with clinical PCa.RESULTS In cohort 1,MKI67 expression was correlated with prostate-specific antigen(PSA),Gleason Score,T stage,and N stage.The receiver operating characteristic(ROC)curve showed a strong diagnostic ability,and the Kaplan-Meier method demonstrated that MKI67 expression was negatively associated with the progression-free interval(PFI).The time-ROC curve displayed a weak prognostic capability for MKI67 expression in PCa.In cohort 2,MKI67 expression was significantly related to the Gleason Score,T stage,and N stage;however,it was negatively associated with the PFI.The time-ROC curve revealed the stronger prognostic capability of MKI67 in patients with PCa.Multivariate COX regression analysis was performed to select risk factors,including PSA level,N stage,and MKI67 expression.A nomogram was established to predict the 3-year PFI.CONCLUSION MKI67 expression was positively associated with the Gleason Score,T stage,and N stage and showed a strong diagnostic and prognostic ability in PCa.

Genetic and epigenetic targets of natural dietary compounds as anti-Alzheimer's agents

Alzheimer’s disease is a progressive neurodegenerative disorder and the most common cause of dementia that principally affects older adults.Pathogenic factors,such as oxidative stress,an increase in acetylcholinesterase activity,mitochondrial dysfunction,genotoxicity,and neuroinflammation are present in this syndrome,which leads to neurodegeneration.Neurodegenerative pathologies such as Alzheimer’s disease are considered late-onset diseases caused by the complex combination of genetic,epigenetic,and environmental factors.There are two main types of Alzheimer’s disease,known as familial Alzheimer’s disease(onset<65 years)and late-onset or sporadic Alzheimer’s disease(onset≥65 years).Patients with familial Alzheimer’s disease inherit the disease due to rare mutations on the amyloid precursor protein(APP),presenilin 1 and 2(PSEN1 and PSEN2)genes in an autosomaldominantly fashion with closely 100%penetrance.In contrast,a different picture seems to emerge for sporadic Alzheimer’s disease,which exhibits numerous non-Mendelian anomalies suggesting an epigenetic component in its etiology.Importantly,the fundamental pathophysiological mechanisms driving Alzheimer’s disease are interfaced with epigenetic dysregulation.However,the dynamic nature of epigenetics seems to open up new avenues and hope in regenerative neurogenesis to improve brain repair in Alzheimer’s disease or following injury or stroke in humans.In recent years,there has been an increase in interest in using natural products for the treatment of neurodegenerative illnesses such as Alzheimer’s disease.Through epigenetic mechanisms,such as DNA methylation,non-coding RNAs,histone modification,and chromatin conformation regulation,natural compounds appear to exert neuroprotective effects.While we do not purport to cover every in this work,we do attempt to illustrate how various phytochemical compounds regulate the epigenetic effects of a few Alzheimer’s disease-related genes.

Genetically modified non-human primate models for research on neurodegenerative diseases

Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(HD),and amyotrophic lateral sclerosis(ALS).Currently,there are no therapies available that can delay,stop,or reverse the pathological progression of NDs in clinical settings.As the population ages,NDs are imposing a huge burden on public health systems and affected families.Animal models are important tools for preclinical investigations to understand disease pathogenesis and test potential treatments.While numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms,the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation gap.Old World nonhuman primates(NHPs),such as rhesus,cynomolgus,and vervet monkeys,are phylogenetically,physiologically,biochemically,and behaviorally most relevant to humans.This is particularly evident in the similarity of the structure and function of their central nervous systems,rendering such species uniquely valuable for neuroscience research.Recently,the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel mechanisms.This review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained,as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.

Expert Experience and Data-Driven Based Hybrid Fault Diagnosis for High-SpeedWire Rod Finishing Mills

The reliable operation of high-speed wire rod finishing mills is crucial in the steel production enterprise.As complex system-level equipment,it is difficult for high-speed wire rod finishing mills to realize fault location and real-time monitoring.To solve the above problems,an expert experience and data-driven-based hybrid fault diagnosis method for high-speed wire rod finishing mills is proposed in this paper.First,based on its mechanical structure,time and frequency domain analysis are improved in fault feature extraction.The approach of combining virtual value,peak value with kurtosis value index,is adopted in time domain analysis.Speed adjustment and side frequency analysis are proposed in frequency domain analysis to obtain accurate component characteristic frequency and its corresponding sideband.Then,according to time and frequency domain characteristics,fault location based on expert experience is proposed to get an accurate fault result.Finally,the proposed method is implemented in the equipment intelligent diagnosis system.By taking an equipment fault on site,for example,the effectiveness of the proposed method is illustrated in the system.

Pathogenesis,clinical manifestations,diagnosis,and treatment progress of achalasia of cardia

Achalasia cardia,type of esophageal dynamic disorder,is a relatively rare primary motor esophageal disease characterized by the functional loss of plexus ganglion cells in the distal esophagus and lower esophageal sphincter.Loss of function of the distal and lower esophageal sphincter ganglion cells is the main cause of achalasia cardia,and is more likely to occur in the elderly.Histological changes in the esophageal mucosa are considered pathogenic;however,studies have found that inflammation and genetic changes at the molecular level may also cause achalasia cardia,resulting in dysphagia,reflux,aspiration,retrosternal pain,and weight loss.Currently,the treatment options for achalasia focus on reducing the resting pressure of the lower esophageal sphincter,helping to empty the esophagus and relieve symptoms.Treatment measures include botulinum toxin injection,inflatable dilation,stent insertion,and surgical myotomy(open or laparoscopic).Surgical procedures are often subject to controversy owing to concerns about safety and effectiveness,particularly in older patients.Herein,we review clinical epidemiological and experimental data to determine the prevalence,pathogenesis,clinical presentation,diagnostic criteria,and treatment options for achalasia to support its clinical management.

Advances and future directions in keloid research:Pathogenesis,diagnosis and personalized treatment strategies

Keloids,which are abnormal manifestations of wound healing,can result in significant functional impairment and aesthetic deformities.The pathogenesis of keloids is multifaceted and complex and influenced by various factors,such as genetics,the environment,and immune responses.The evolution of keloid treatment has progressed from traditional surgical excision to a contemporary combination of therapies including injection and radiation treatments,among others.This article provides a comprehensive review of keloid pathogenesis and treatment,emphasizing the latest advances in the field.Ultimately,this review underscores the necessity for continued research to enhance our understanding of keloid pathogenesis and to devise more effective treatments for this challenging condition.

Genetic susceptibility loci of lung cancer are associated with malignant risk of pulmonary nodules and improve malignancy diagnosis based on CEA levels

Objective:The heightened prevalence of pulmonary nodules(PN)has escalated its significance as a public health concern.While the precise identification of high-risk PN carriers for malignancy remains an ongoing challenge,genetic variants hold potentials as determinants of disease susceptibility that can aid in diagnosis.Yet,current understanding of the genetic loci associated with malignant PN(MPN)risk is limited.Methods:A frequency-matched case-control study was performed,comprising 247 MPN cases and 412 benign NP(BNP)controls.We genotyped 11 established susceptibility loci for lung cancer in a Chinese cohort.Loci associated with MPN risk were utilized to compute a polygenic risk score(PRS).This PRS was subsequently incorporated into the diagnostic evaluation of MPNs,with emphasis on serum tumor biomarkers.Results:Loci rs10429489G>A,rs17038564A>G,and rs12265047A>G were identified as being associated with an increased risk of MPNs.The PRS,formulated from the cumulative risk effects of these loci,correlated with the malignant risk of PNs in a dose-dependent fashion.A high PRS was found to amplify the MPN risk by 156%in comparison to a low PRS[odds ratio(OR)=2.56,95%confidence interval(95%CI),1.40−4.67].Notably,the PRS was observed to enhance the diagnostic accuracy of serum carcinoembryonic antigen(CEA)in distinguishing MPNs from BPNs,with diagnostic values rising from 0.716 to 0.861 across low-to high-PRS categories.Further bioinformatics investigations pinpointed rs10429489G>A as an expression quantitative trait locus.Conclusions:Loci rs10429489G>A,rs17038564A>G,and rs12265047A>G contribute to MPN risk and augment the diagnostic precision for MPNs based on serum CEA concentrations.

Clinical and genetic diagnosis of autosomal dominant osteopetrosis typeⅡin a Chinese family:A case report

BACKGROUND Osteopetrosis is a rare genetic disorder characterized by increased bone density due to defective bone resorption of osteoclasts.Approximately,80%of autosomal dominant osteopetrosis type II(ADO-II)patients were usually affected by heterozygous dominant mutations in the chloride voltage-gated channel 7(ClCN7)gene and present early-onset osteoarthritis or recurrent fractures.In this study,we report a case of persistent joint pain without bone injury or underlying history.CASE SUMMARY We report a 53-year-old female with joint pain who was accidentally diagnosed with ADO-II.The clinical diagnosis was based on increased bone density and typical radiographic features.Two heterozygous mutations in the ClCN7 and Tcell immune regulator 1(TCIRG1)genes by whole exome sequencing were identified in the patient and her daughter.The missense mutation(c.857G>A)occurred in the CLCN7 gene p.R286Q,which is highly conserved across species.The TCIRG1 gene point mutation(c.714-20G>A)in intron 7(near the splicing site of exon 7)had no effect on subsequent transcription.CONCLUSION This ADO-II case had a pathogenic CLCN7 mutation and late onset without the usual clinical symptoms.For the diagnosis and assessment of the prognosis for osteopetrosis,genetic analysis is advised.

A Novel Motor Fault Diagnosis Method Based on Generative Adversarial Learning with Distribution Fusion of Discrete Working Conditions

Many kinds of electrical equipment are used in civil and building engineering.The motor is one of the main power components of this electrical equipment,which can provide stable power output.During the long-term use of motors,various motor faults may occur,which affects the normal use of electrical equipment and even causes accidents.It is significant to apply fault diagnosis for the motors at the construction site.Aiming at the problem that signal data of faulty motor lack diversity,this research designs a multi-layer perceptron Wasserstein generative adversarial network,which is used to enhance training data through distribution fusion.A discrete wavelet decomposition algorithm is employed to extract the low-frequency wavelet coefficients from the original motor current signals.These are used to train themulti-layer perceptron Wasserstein generative adversarial model.Then,the trainedmodel is applied to generate fake current wavelet coefficients with the fused distribution.A motor fault classification model consisting of a feature extractor and pattern recognizer is built based on perceptron.The data augmentation experiment shows that the fake dataset has a larger distribution than the real dataset.The classification model trained on a real dataset,fake dataset and combined dataset achieves 21.5%,87.2%,and 90.1%prediction accuracy on the unseen real data,respectively.The results indicate that the proposed data augmentation method can effectively generate fake data with the fused distribution.The motor fault classification model trained on a fake dataset has better generalization performance than that trained on a real dataset.