Background: and Purpose Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis. Methods: This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed. Results: Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; p=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; p=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; p=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I–II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III–IV VBFAs. Conclusions Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I–II VBFAs, although residual confounding cannot be excluded.

Objective:X-linked non-syndromic hearing loss is an extremely rare type of hearing impairment. This study conducted a phenotypic and genetic analysis of a family with X-linked dominant inheritance to explore the causes of hearing loss. Methods:Clinical data were collected from a patient with non-syndromic hearing loss who visited the Otorhinolaryngology Department of the First Affiliated Hospital of Zhengzhou University in June 2023. Phenotypic and genetic analyses were performed on family members, including audiometric tests, whole-exome sequencing, and PCR-Sanger sequencing verification. Audiological assessments comprised pure-tone audiometry, impedance audiometry, auditory brainstem response, and otoacoustic emission tests. Results:The affected individuals in this pedigree have X-linked dominant non-syndromic deafness caused by mutations in the SMPX gene. The proband, along with their mother and maternal grandmother, exhibit varying degrees of sensorineural hearing loss. Whole-exome sequencing revealed a novel pathogenic variant, NM_014332.3: c. 133-2A>C, in the SMPX gene in the proband. Sanger sequencing confirmed that the proband, proband's mother, and grandmother all carried this pathogenic variant. Conclusion:This study reports a novel pathogenic variant in the SMPX gene, providing additional medical evidence for the diagnosis and treatment of X-linked dominant inherited non-syndromic hearing loss. It enriches the mutation spectrum of the SMPX gene.
Humans ; Pedigree ; Mutation ; Phenotype ; Male ; Hearing Loss, Sensorineural/genetics* ; Exome Sequencing ; Female ; Adult ; Hearing Loss/genetics* ; Evoked Potentials, Auditory, Brain Stem ; Muscle Proteins

Multiple sclerosis(MS)is a complex autoimmune disorder characterized by inflammatory demyelination in the central nervous system.Prominent symptoms include damage to myelin sheaths in the brain,optic nerve,and spinal cord,as well as axonal dysfunction;however,the exact causes and mechanisms of MS remain unclear.Genetic and environmental factors are thought to interact via autoimmune mechanisms,potentially triggering the disease.Recent studies suggest that abnormal activation of the NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome may play a critical role in the pathogenesis of MS.In this context,this review summarizes the molecular mechanisms underlying NLRP3 activation and its connection to MS,considering relevant literature from the past decade.The findings aim to provide insights into the progression of MS and to identify potential therapeutic strategies by elucidating the underlying mechanisms.

Objective:To evaluate the role of whole exome sequencing（WES）in the etiological diagnosis and precision medicine management of patients with urolithiasis.Methods:We conducted a retrospective review of 21 patients with urolithiasis and pathogenic gene mutations identified by WES at The Second Affiliated Hospital of Zhengzhou University between April 2019 and March 2025. The cohort included 13 males and 8 females，with a mean age of（18.9 ± 11.1）years；18 patients were under 25 years old. Clinical presentations included nephrocalcinosis（8 patients）and urinary tract calculi（13 patients），with five patients exhibiting extra-renal manifestations such as renal tubular acidosis and hyperaldosteronism. Stone composition analysis identified calcium oxalate（16 patients），cystine（4 patients），and carbonate apatite（1 patient）. Metabolic abnormalities were prevalent，including hypocitraturia（11 patients），hyperoxaluria（8 patients），and hypercalciuria（7 patients），with eight patients presenting two or more concurrent disorders. All patients underwent WES and comprehensive metabolic evaluation. Sequencing was performed on an Illumina Hiseq4000 platform，achieving a mean depth of > 100× and coverage of > 98% in target regions. Variants were classified according to the American College of Medical Genetics and Genomics（ACMG）guidelines.Results:WES identified 12 distinct genes across autosomal recessive（9 genes： AGXT， GRHPR， ATP6V1B1， SLC12A1， KCNJ1， SLC3A1， SLC7A9， SLC34A3， WFS1），autosomal dominant（2 genes： CASR， ADCY10），and X-linked recessive（1 gene： CLCN5）inheritance patterns. Genotype-phenotype correlations revealed mutations associated with primary hyperoxaluria（8 patients），hypercalciuria（7 patients），and renal malformation due to a WFS1 mutation（1 patient）. A positive genetic diagnosis was achieved in 100% of patients with either urinary oxalate > 1 000 μmol/24 h or cystine stones. 8 patients received a diagnosis of hereditary stone disease at their first presentation（non-delayed group），while 13 experienced a mean diagnostic delay of（9.6 ± 3.9）years. The delayed diagnosis group had a significantly older age at initial stone onset［（10.2 ± 5.3）years vs.（6.8 ± 3.1）years， P = 0.03］and a higher incidence of impaired renal function（6 patients vs. 1 patient， P = 0.04）. Analysis of diagnostic delay by gene subgroup showed delays in 2/4 patients with cystinuria［ SLC3A1/ SLC7A9；（8.2 ± 3.5）years］，5/8 with primary hyperoxaluria［ AGXT/ GRHPR；（10.5 ± 4.1）years］，5/7 with hypercalciuria-related genes［ CASR/ ADCY10/ SLC12A1/ KCNJ1/ SLC34A3；（9.8 ± 3.8）years］，and 1/2 with other genes［ ATP6V1B1/ WFS1/ CLCN5；（7.6 ± 2.2）years］. Among 32 mutation sites detected，21 were classified as pathogenic/likely pathogenic and 11 as variants of uncertain significance. Four novel mutations were identified： ATP6V1B1（presenting with renal tubular acidosis，nephrocalcinosis，and hypocitraturia）， WFS1（presenting with renal malrotation，hydronephrosis，and stones without metabolic abnormalities）， SLC12A1（presenting with Bartter syndrome type 1，chronic renal insufficiency，hypercalciuria，hypocitraturia，alkalosis，and hyperaldosteronism），and SLC3A1（presenting with bilateral renal stones and cystinuria）. Conclusions:WES is crucial in identifying the underlying etiology of urolithiasis and can guide targeted treatment. We recommend early WES for patients with an initial stone presentation before age 25，those with nephrocalcinosis，or those with abnormal metabolic workups to facilitate precise diagnosis and preventive care.

Objective:The aim of this study is to analyze the clinical characteristics and genetic variants of a late-onset auditory neuropathy pedigree caused by maternally inherited- mitochondrial mutation.Methods:A male proband who presented with bilateral sensorineural hearing loss at Henan Children′s Hospital in September 2023 was chosen, along with his family members (4 generations, 20 individuals) as the study subjects. Data from this pedigree were collected, organized, and analyzed for clinical genetic characteristics. Medical histories were obtained from family members, pedigree charts were drawn, audiological, imaging, and physical examinations were conducted. Pathogenic genes and mutations were screened using high-throughput sequencing. Sanger sequencing was employed for variant confirmation and segregation validation in the family.Results:In this family, a total of 12 members (10 members collected) had sensorineural hearing loss, characterized by late-onset hearing impairment with an onset age ranging from 9 to 30 years. The patients exhibited poor speech recognition rates, and audiometric examinations are consistent with auditory neuropathy. There was no history of ototoxic drug use. High-throughput sequencing identified the variant NC_012920.1:m.7471dup in the mitochondrial MT-TS1 gene as the pathogenic variant. Sanger sequencing results confirmed that the pathogenic gene mutation site perfectly co-segregated with the auditory neuropathy phenotype in this family. According to the classification criteria and guidelines for genetic variations by the American College of Medical Genetics and Genomics, the variant was classified as a pathogenic mutation. Conclusion:The mitochondrial MT-TS1 gene mutation m.7471dup is considered to be the pathogenic cause in this late-onset auditory neuropathy pedigree.

Multiple sclerosis(MS)is a complex autoimmune disorder characterized by inflammatory demyelination in the central nervous system.Prominent symptoms include damage to myelin sheaths in the brain,optic nerve,and spinal cord,as well as axonal dysfunction;however,the exact causes and mechanisms of MS remain unclear.Genetic and environmental factors are thought to interact via autoimmune mechanisms,potentially triggering the disease.Recent studies suggest that abnormal activation of the NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome may play a critical role in the pathogenesis of MS.In this context,this review summarizes the molecular mechanisms underlying NLRP3 activation and its connection to MS,considering relevant literature from the past decade.The findings aim to provide insights into the progression of MS and to identify potential therapeutic strategies by elucidating the underlying mechanisms.

Objective:To evaluate the role of whole exome sequencing（WES）in the etiological diagnosis and precision medicine management of patients with urolithiasis.Methods:We conducted a retrospective review of 21 patients with urolithiasis and pathogenic gene mutations identified by WES at The Second Affiliated Hospital of Zhengzhou University between April 2019 and March 2025. The cohort included 13 males and 8 females，with a mean age of（18.9 ± 11.1）years；18 patients were under 25 years old. Clinical presentations included nephrocalcinosis（8 patients）and urinary tract calculi（13 patients），with five patients exhibiting extra-renal manifestations such as renal tubular acidosis and hyperaldosteronism. Stone composition analysis identified calcium oxalate（16 patients），cystine（4 patients），and carbonate apatite（1 patient）. Metabolic abnormalities were prevalent，including hypocitraturia（11 patients），hyperoxaluria（8 patients），and hypercalciuria（7 patients），with eight patients presenting two or more concurrent disorders. All patients underwent WES and comprehensive metabolic evaluation. Sequencing was performed on an Illumina Hiseq4000 platform，achieving a mean depth of > 100× and coverage of > 98% in target regions. Variants were classified according to the American College of Medical Genetics and Genomics（ACMG）guidelines.Results:WES identified 12 distinct genes across autosomal recessive（9 genes： AGXT， GRHPR， ATP6V1B1， SLC12A1， KCNJ1， SLC3A1， SLC7A9， SLC34A3， WFS1），autosomal dominant（2 genes： CASR， ADCY10），and X-linked recessive（1 gene： CLCN5）inheritance patterns. Genotype-phenotype correlations revealed mutations associated with primary hyperoxaluria（8 patients），hypercalciuria（7 patients），and renal malformation due to a WFS1 mutation（1 patient）. A positive genetic diagnosis was achieved in 100% of patients with either urinary oxalate > 1 000 μmol/24 h or cystine stones. 8 patients received a diagnosis of hereditary stone disease at their first presentation（non-delayed group），while 13 experienced a mean diagnostic delay of（9.6 ± 3.9）years. The delayed diagnosis group had a significantly older age at initial stone onset［（10.2 ± 5.3）years vs.（6.8 ± 3.1）years， P = 0.03］and a higher incidence of impaired renal function（6 patients vs. 1 patient， P = 0.04）. Analysis of diagnostic delay by gene subgroup showed delays in 2/4 patients with cystinuria［ SLC3A1/ SLC7A9；（8.2 ± 3.5）years］，5/8 with primary hyperoxaluria［ AGXT/ GRHPR；（10.5 ± 4.1）years］，5/7 with hypercalciuria-related genes［ CASR/ ADCY10/ SLC12A1/ KCNJ1/ SLC34A3；（9.8 ± 3.8）years］，and 1/2 with other genes［ ATP6V1B1/ WFS1/ CLCN5；（7.6 ± 2.2）years］. Among 32 mutation sites detected，21 were classified as pathogenic/likely pathogenic and 11 as variants of uncertain significance. Four novel mutations were identified： ATP6V1B1（presenting with renal tubular acidosis，nephrocalcinosis，and hypocitraturia）， WFS1（presenting with renal malrotation，hydronephrosis，and stones without metabolic abnormalities）， SLC12A1（presenting with Bartter syndrome type 1，chronic renal insufficiency，hypercalciuria，hypocitraturia，alkalosis，and hyperaldosteronism），and SLC3A1（presenting with bilateral renal stones and cystinuria）. Conclusions:WES is crucial in identifying the underlying etiology of urolithiasis and can guide targeted treatment. We recommend early WES for patients with an initial stone presentation before age 25，those with nephrocalcinosis，or those with abnormal metabolic workups to facilitate precise diagnosis and preventive care.

Objective:The aim of this study is to analyze the clinical characteristics and genetic variants of a late-onset auditory neuropathy pedigree caused by maternally inherited- mitochondrial mutation.Methods:A male proband who presented with bilateral sensorineural hearing loss at Henan Children′s Hospital in September 2023 was chosen, along with his family members (4 generations, 20 individuals) as the study subjects. Data from this pedigree were collected, organized, and analyzed for clinical genetic characteristics. Medical histories were obtained from family members, pedigree charts were drawn, audiological, imaging, and physical examinations were conducted. Pathogenic genes and mutations were screened using high-throughput sequencing. Sanger sequencing was employed for variant confirmation and segregation validation in the family.Results:In this family, a total of 12 members (10 members collected) had sensorineural hearing loss, characterized by late-onset hearing impairment with an onset age ranging from 9 to 30 years. The patients exhibited poor speech recognition rates, and audiometric examinations are consistent with auditory neuropathy. There was no history of ototoxic drug use. High-throughput sequencing identified the variant NC_012920.1:m.7471dup in the mitochondrial MT-TS1 gene as the pathogenic variant. Sanger sequencing results confirmed that the pathogenic gene mutation site perfectly co-segregated with the auditory neuropathy phenotype in this family. According to the classification criteria and guidelines for genetic variations by the American College of Medical Genetics and Genomics, the variant was classified as a pathogenic mutation. Conclusion:The mitochondrial MT-TS1 gene mutation m.7471dup is considered to be the pathogenic cause in this late-onset auditory neuropathy pedigree.

To accurately capture and effectively integrate the spatiotemporal features of electroencephalogram (EEG) signals for the purpose of improving the accuracy of EEG-based emotion recognition, this paper proposes a new method combining independent component analysis-recurrence plot with an improved EfficientNet version 2 (EfficientNetV2). First, independent component analysis is used to extract independent components containing spatial information from key channels of the EEG signals. These components are then converted into two-dimensional images using recurrence plot to better extract emotional features from the temporal information. Finally, the two-dimensional images are input into an improved EfficientNetV2, which incorporates a global attention mechanism and a triplet attention mechanism, and the emotion classification is output by the fully connected layer. To validate the effectiveness of the proposed method, this study conducts comparative experiments, channel selection experiments and ablation experiments based on the Shanghai Jiao Tong University Emotion Electroencephalogram Dataset (SEED). The results demonstrate that the average recognition accuracy of our method is 96.77%, which is significantly superior to existing methods, offering a novel perspective for research on EEG-based emotion recognition.
Electroencephalography/methods* ; Emotions ; Humans ; Signal Processing, Computer-Assisted ; Principal Component Analysis ; Algorithms ; Convolutional Neural Networks

Objective:To investigate the clinical features, molecular etiology, and treatment of a family with Treacher Collins Syndrome 2 (TCS2).Methods:Information of the proband (female, 8 years old) including medical history and family history was collected. Physical examination and examinations concerning laboratory, audiology, and radiology were performed on the proband. Physical examination was also performed on the family members. Genomic DNA of proband was extracted for whole exome sequencing, and then the genomic DNA of family members was extracted for Sanger sequencing. POLR1D and TCS2 related literatures published before August 31,2023 were searched and sifted in PubMed and CKNI databases. The clinical characteristics of TCS2 were summarized. Results:The proband had poor hearing since childhood, with pure tone audiometry indicating conductive hearing loss. She had a smaller jaw, bilateral preauricular fistulas and cup-shaped ear deformities. Temporal bone CT scan revealed deformities in the left external ear canal, bilateral middle ear and inner ear. A bone-conduction hearing aid device was surgically implanted, resulting in restoration of almost normal hearing levels. The proband′s mother also had a slightly smaller jaw. Genetic analysis revealed a novel heterozygous variant NM_015972.4:c.38_47del in the POLR1D gene in the proband, which was inherited from her mother. A review of the literature revealed no clear evidence of genotype-phenotype correlation in TCS2. Conclusions:Molecular diagnosis plays a vital role in the diagnosis of TCS2. Patients with normal facial phenotype may be carriers of pathogenic variants in the POLR1D gene and have the risk of passing it to the offsprings with complete penetrance. Proper bone conductive hearing devices can improve the quality of life of TCS2 patients.