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

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: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.

Background::Growth retardation is a common complication of chronic kidney disease in children, which can be partially relieved after renal transplantation. This study aimed to develop and validate a predictive model for growth patterns of children with end-stage renal disease (ESRD) after kidney transplantation using machine learning algorithms based on genomic and clinical variables.Methods::A retrospective cohort of 110 children who received kidney transplants between May 2013 and September 2021 at the First Affiliated Hospital of Zhengzhou University were recruited for whole-exome sequencing (WES), and another 39 children who underwent transplant from October 2021 to March 2022 were enrolled for external validation. Based on previous studies, we comprehensively collected 729 height-related single-nucleotide polymorphisms (SNPs) in exon regions. Seven machine learning algorithms and 10-fold cross-validation analysis were employed for model construction.Results::The 110 children were divided into two groups according to change in height-for-age Z-score. After univariate analysis, age and 19 SNPs were incorporated into the model and validated. The random forest model showed the best prediction efficacy with an accuracy of 0.8125 and an area under curve (AUC) of 0.924, and also performed well in the external validation cohort (accuracy, 0.7949; AUC, 0.796). Conclusions::A model with good performance for predicting post-transplant growth patterns in children based on SNPs and clinical variables was constructed and validated using machine learning algorithms. The model is expected to guide clinicians in the management of children after renal transplantation, including the use of growth hormone, glucocorticoid withdrawal, and nutritional supplementation, to alleviate growth retardation in children with ESRD.

Restricted and repetitive behaviors is the characteristic clinical manifestation of many neuropsychiatric diseases, which seriously affects the work, study and daily communication of patients, and brings huge mental and economic burden to the family and society.Its causes are complex and its manifestations are diverse.Current studies have shown that microglia is closely related to the occurrence of restricted and repetitive behaviors, and the in-depth study of microglia has become a research hotspot to explore the mechanism of restricted and repetitive behaviors.In recent years, studies have found that restricted and repetitive behaviors of various neuropsychiatric diseases (such as frontotemporal dementia, obsessive-compulsive disorder, autism spectrum disorder) are related to microglia.However, reliable evidence for the exact mechanism of microglia involved in restricted and repetitive behaviors remains lacking.This article reviews the recent research progress of microglia involved in restricted and repetitive behaviors.It is expected to provide a new theoretical basis and therapeutic targeting cell for the development and treatment of neuropsychiatric diseases related to restricted and repetitive behaviors in the future.

Objective To investigate the correlation between serum renal injury molecule-1(KIM-1)and neutrophil gelatinase-associated lipocalin(NGAL)in the remission of diabetic kidney disease(DKD)after gastric bypass surgery in obese DKD patients.Methods Seventy-nine obese patients with DKD who received gastric bypass surgery in our hospital from January 2021 to January 2022 were selected and divided into DKD remission group(n= 47)and DKD non-remission group(n=32)according to whether UACR decreased to normal level after surgery.Preoperative and postoperative general data were collected and biochemical indices,serum KIM-1 and NGAL levels were detected.Results None of the 79 obese DKD patients had intraoperative complications or switched to laparotomy.BMI,FPG,HbA1c,SBP,DBP,TC,TG,LDL-C,SUA,UACR,KIM-1 and NGAL were decreased after surgery,while HDL-C was increased after surgery(P＜0.05).SBP,DBP,Scr,BUN,UACR,KIM-1 and NGAL in remission group were lower than those in non-remission group(P＜0.05).Spearman correlation analysis showed that the levels of KIM-1 and NGAL were positively correlated with Scr,BUN and UACR(P＜0.05),but negatively correlated with eGFR(P＜0.05).Logistic regression analysis showed that SBP,UACR,KIM-1 and NGAL were influencing factors for DKD remission after gastric bypass surgery.The areas under ROC curve of serum KIM-1,NGAL and combined prediction of DKD remission were 0.801,0.757 and 0.863,respectively.Conclusion Serum KIM-1 and NGAL can predict DKD remission in obese DKD patients after gastric bypass surgery.

Objective:To observe the clinical and imaging characteristics of radiation optic neuropathy (RION).Methods:A retrospective clinical study. A total of 43 patients (69 eyes) who were diagnosed with RION at the Chinese PLA General Hospital from 2010 to 2021 were included in this study. There were 23 males (36 eyes) and 20 females (33 eyes). The age of patients at the time of radiation therapy was 49.54±13.14 years. The main dose of radiotherapy for lesions was 59.83±14.12 Gy. Sixteen patients were treated with combined chemotherapeutic agents. The clinical details of best corrected visual acuity (BCVA) and color photography of the fundus were collected. Forty-six eyes underwent optical coherence tomography (OCT), visual field were examined in 30 eyes, magnetic resonance imaging (MRI) were performed in 40 eyes. The BCVA examination was performed using Snellen visual acuity chart, which was converted to minimum resolution angle logarithm (logMAR) visual acuity during recording. Hyperbaric oxygen therapy (HBOT) was performed in 10 patients (13 eyes), 9 patients (12 eyes) were treated with intravenous methylprednisolone (IVMP), 12 patients (23 eyes) were treated with HBOT combined with IVMP and control group of 12 patients (21 eyes) were only treated with basal treatment. And grouped accordingly. To observe the changes in onset, recovery, and final BCVA of the affected eye as well as thickness changes of the retinal nerve fiber layer (RNFL) of the optic disc and inner limiting membrane-retinal pigment epithelium (ILM-RPE) layer of the macular area, and final outcome of BCVA with different treatment modalities in affected eyes. The RNFL and ILM-RPE layer thicknesses were compared between patients with different disease duration as well as between treatment regimens using independent samples t-test. Results:Of the 43 cases, vision loss was monocular in 17 patients (39.53%, 17/43) and binocular in 26 patients (60.47%, 26/43). The latency from radiotherapy to onset of visual loss was 36.33±30.48 months. The duration of RION ranged from 1 week to 10 years, in which the disease duration of 37 eyes ≤2 months. Subacute visual acuity loss was present in 41 eyes. logMAR BCVA<1.0, 1.0-0.3, >0.3 were 45, 15, and 9 eyes, respectively. Optic disc pallor and optic disc edema were found in 10 (27.03%, 10/37), 3 (8.11%, 3/37) eyes, respectively, within 2 months. The superior RNFL [95% confidence interval ( CI) 2.08-66.56, P=0.038] and the outer circle of the inner limiting membrane to retinal pigment epithelium (ILM-RPE) (95% CI 4.37-45.39, P=0.021) layer thinned significantly during the first month. The center of the ILM-RPE layer thickened (95% CI-32.95--4.20, P=0.015) significantly during the first two months. The inner circle temporal quadrant of the ILM-RPE layer thickened (95% CI -42.22--3.83, P=0.022) significantly from the third to sixth month, and the RNFL except for the temporal quadrants and the average RNFL, inner circle superior quadrant and outer circle of the ILM-RPE layer thinned significantly after 6 months ( P<0.05). Among the 40 eyes that underwent MRI examination, 33 eyes (82.50%, 33/40) were affected by T1 enhancement of optic nerve, including 23 eyes (69.70%, 23/33) in intracranial segment; 12 eyes with thickening and long T2 signal (36.36%, 12/33). After treatment, BCVA was restored in 17 eyes (24.6%, 17/69) and final BCVA improved in 9 eyes (13.0%, 9/69). There was no significant difference between HBOT, IVMP and HBOT combined with IVMP therapy in improving BCVA recovery or final BCVA compared with the control group, respectively ( t=-1.04, 0.61, 1.31,-1.47, -0.42, 0.46; P>0.05). Conclusions:The structural damage of the RNFL and ILM-RPE layer occurred during the first month, the RNFL showed progressive thinning during the follow-up period, while the ILM-RPE layer showed thinning-thickening-thinning. MRI shows T1 enhancement of the optic chiasma and segments of the optic nerve, and the enhanced segments are usually accompanied by thickening and long T2. HBOT and IVMP have no obvious effect on RION.

The Genome Warehouse (GWH) is a public repository housing genome assembly data for a wide range of species and delivering a series of web services for genome data submission, storage, release, and sharing. As one of the core resources in the National Genomics Data Center (NGDC), part of the China National Center for Bioinformation (CNCB;https://ngdc.cncb.ac.cn), GWH accepts both full and partial (chloroplast, mitochondrion, and plasmid) genome sequences with different assembly levels, as well as an update of existing genome assemblies. For each assembly, GWH collects detailed genome-related metadata of biological project, biological sample, and genome assembly, in addition to genome sequence and annotation. To archive high-quality genome sequences and annotations, GWH is equipped with a uniform and standardized procedure for quality control. Besides basic browse and search functionalities, all released genome sequences and annotations can be visualized with JBrowse. By May 21, 2021, GWH has received 19,124 direct submissions covering a diversity of 1108 species and has released 8772 of them. Collectively, GWH serves as an important resource for genome-scale data management and provides free and publicly accessible data to support research activities throughout the world. GWH is publicly accessible at https://ngdc.cncb.ac.cn/gwh.

Objective: To explore the clinical practice of delivering radiotherapy during the outbreak of 2019 novel coronavirus disease(COVID-19). Methods: During this epidemic period, available methods including but not limited to: strict disinfection, body temperature monitoring, learning relevant knowledge by all staffs to ensure the safety of radiotherapy treatment. Relevant data including proportion of radiotherapy, time from scanning to the first time of radiation delivery and degree of satisfaction in the view of staffs and patients, respectively. Results: A total of 60 patients received radiation therapy in the department of radiotherapy of Zhejiang Provincial People’s Hospital (2020-02-11). Compared with the same period in 2019 (after the Spring Festival), the total number of patients receiving radiotherapy was decreased from 72 to 60(83.3%). Among them, the number of patients receiving palliative radiation therapy decreased significantly, while the proportion of radical, preoperative and/or postoperative radiotherapy/radiochemotherapy did not significantly decrease. There was significant difference between different years (χ²=6.967, P<0.05). The median time for newly admitted patients to receive radiotherapy was two days, which was not significantly longer than the interval in 2019 (P>0.05). Staffs and patients were generally satisfied with the current prevention measures. Conclusions Using a variety of prevention and control methods, and taking full account of medical safety and patient benefits, radiation-related activities can be carried out during the epidemic.