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 analyze the status of registration of clinical trials of radiopharmaceuticals in China, and to provide reference for the development and clinical application of radiopharmaceuticals.Methods:By searching the clinical trial registration and information disclosure platform of the Center for Drug Evaluation of the National Medical Products Administration (NMPA), the data on clinical trials of radiopharmaceuticals registered from 2014 to 2024 were collected and analyzed for trial design, administered dose, common indications, and geographical distribution.Results:A total of 77 clinical trials were included. The Compound Annual Growth Rate for the number of projects from 2014 to 2024 was 40%. Diagnostic radiopharmaceuticals were predominantly based on 18F and 99Tc m, while therapeutic radiopharmaceuticals primarily utilized 177Lu and 90Y. All indications were concentrated in the field of oncology. Regarding trial design, non-randomized (71.4%), open-label (89.6%), and single-arm (66.2%) trials accounted for the highest proportions. Geographical distribution showed Beijing (29 trials), Shanghai (18 trials), and Jiangsu province (14 trials) as the regions with the highest concentration of clinical trials. Conclusions:Radiopharmaceutical clinical trials in China have shown rapid growth. However, research remains predominantly focused on oncology, with a relatively high proportion of early-stage trials. In order to fully utilize the potentials of radiopharmaceuticals and improve the quality of clinical trials, nuclear medicine researches should broaden therapeutic applications, implement prudently administerd dose in clinical trials, and implement optimized radiation protection procedures across all clinical trial centers.

Objective:To analyze the effects of cytomegalovirus (CMV) infection on gene expression and signaling pathways in preauricular somatic cells, and to explore potential intervention approaches for neonatal hearing loss caused by CMV infection.Methods:CMV infection data (GSE234062) were retrieved and downloaded from the GEO database. R studio software was used to analyze the differentially expressed genes (DEGs) between the CMV-infected group and the control group. ExpressAnalyst and String tools were employed to analyze the enrichment of DEGs in signaling pathways, biological processes, molecular functions, and protein-protein interactions.Results:After CMV infection of preauricular somatic cells, the expression levels of viral RNA and green fluorescent protein (GFP) RNA increased significantly. Meanwhile, 233 genes were upregulated and 123 genes were downregulated post-infection. Signaling pathway analysis showed that the upregulated genes were mainly enriched in pathways such as calcium ion channels, GABA synapses, morphine addiction, and cGMP-PKG, while the downregulated genes were primarily enriched in pathways including focal adhesion, extracellular matrix (ECM)-receptor interaction, amebiasis, and proteoglycans in cancer. Biological process analysis revealed that the upregulated genes were closely associated with neuron development and cell maturation, whereas the downregulated genes were mainly involved in actin filament-dependent processes, tissue development, and vascular development. Molecular function enrichment analysis indicated that the upregulated genes were mainly clustered in sequence-specific DNA binding, RNA polymerase Ⅱ distal enhancer binding, and G protein-coupled amine receptor activity, while the downregulated genes were closely related to molecular functions such as actin binding, structural molecule activity, and extracellular matrix structure.Conclusions:CMV infection can activate calcium ion channel and GABA synaptic pathways, and impair focal adhesion and ECM-receptor interaction pathways in preauricular somatic cells. This suggests that targeting these related pathways may help alleviate neonatal hearing impairment caused by CMV infection.

Objective:To analyze the status of registration of clinical trials of radiopharmaceuticals in China, and to provide reference for the development and clinical application of radiopharmaceuticals.Methods:By searching the clinical trial registration and information disclosure platform of the Center for Drug Evaluation of the National Medical Products Administration (NMPA), the data on clinical trials of radiopharmaceuticals registered from 2014 to 2024 were collected and analyzed for trial design, administered dose, common indications, and geographical distribution.Results:A total of 77 clinical trials were included. The Compound Annual Growth Rate for the number of projects from 2014 to 2024 was 40%. Diagnostic radiopharmaceuticals were predominantly based on 18F and 99Tc m, while therapeutic radiopharmaceuticals primarily utilized 177Lu and 90Y. All indications were concentrated in the field of oncology. Regarding trial design, non-randomized (71.4%), open-label (89.6%), and single-arm (66.2%) trials accounted for the highest proportions. Geographical distribution showed Beijing (29 trials), Shanghai (18 trials), and Jiangsu province (14 trials) as the regions with the highest concentration of clinical trials. Conclusions:Radiopharmaceutical clinical trials in China have shown rapid growth. However, research remains predominantly focused on oncology, with a relatively high proportion of early-stage trials. In order to fully utilize the potentials of radiopharmaceuticals and improve the quality of clinical trials, nuclear medicine researches should broaden therapeutic applications, implement prudently administerd dose in clinical trials, and implement optimized radiation protection procedures across all clinical trial centers.

Objective:To analyze the effects of cytomegalovirus (CMV) infection on gene expression and signaling pathways in preauricular somatic cells, and to explore potential intervention approaches for neonatal hearing loss caused by CMV infection.Methods:CMV infection data (GSE234062) were retrieved and downloaded from the GEO database. R studio software was used to analyze the differentially expressed genes (DEGs) between the CMV-infected group and the control group. ExpressAnalyst and String tools were employed to analyze the enrichment of DEGs in signaling pathways, biological processes, molecular functions, and protein-protein interactions.Results:After CMV infection of preauricular somatic cells, the expression levels of viral RNA and green fluorescent protein (GFP) RNA increased significantly. Meanwhile, 233 genes were upregulated and 123 genes were downregulated post-infection. Signaling pathway analysis showed that the upregulated genes were mainly enriched in pathways such as calcium ion channels, GABA synapses, morphine addiction, and cGMP-PKG, while the downregulated genes were primarily enriched in pathways including focal adhesion, extracellular matrix (ECM)-receptor interaction, amebiasis, and proteoglycans in cancer. Biological process analysis revealed that the upregulated genes were closely associated with neuron development and cell maturation, whereas the downregulated genes were mainly involved in actin filament-dependent processes, tissue development, and vascular development. Molecular function enrichment analysis indicated that the upregulated genes were mainly clustered in sequence-specific DNA binding, RNA polymerase Ⅱ distal enhancer binding, and G protein-coupled amine receptor activity, while the downregulated genes were closely related to molecular functions such as actin binding, structural molecule activity, and extracellular matrix structure.Conclusions:CMV infection can activate calcium ion channel and GABA synaptic pathways, and impair focal adhesion and ECM-receptor interaction pathways in preauricular somatic cells. This suggests that targeting these related pathways may help alleviate neonatal hearing impairment caused by CMV infection.

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 explore chromosomal copy number variations (CNVs) and pregnancy outcomes in fetuses with mild to moderate isolated ventriculomegaly (IVM), but without other indications for invasive prenatal diagnosis.Methods:A retrospective analysis was conducted on clinical data of 215 singleton pregnancies with mild to moderate IVM (lateral ventricular width≥10-<15 mm) who underwent chromosomal microarray analysis (CMA), not indicated by advanced age, high risk in serum screening or abnormal history of pregnancy, at the Fujian Maternity and Child Health Hospital between June 2016 and March 2023. The 215 fetuses were grouped into mild ( n=167) and moderate ( n=48) IVM;unilateral ( n=142) and bilateral ( n=73) IVM; first diagnosis of IVM before 28 weeks ( n=138) and thereafter ( n=77). Anomalies other than IVM were excluded via three-dimensional color Doppler ultrasound examination between 22 and 26 weeks of gestation. Out of these cases, 129 were confirmed by fetal cranial MRI, 191 underwent chromosomal karyotype analysis, and 202 cases received cytomegalovirus DNA quantification test for amniotic fluid. The detection rates of pathogenic CNVs in various groups were compared using Fisher's exact test. Results:Among the 215 fetuses, 11 cases (5.1%) of chromosomal abnormalities were detected through CMA, including one trisomy 21, five pathogenic CNVs, and five CNVs of uncertain clinical significance. Within the pathogenic CNVs, there were two de novo mutations with 16p11.2 microdeletion and one de novo mutation with 16p11.2 microduplication, while one 16p11.2 microduplication and one Xp22.31 microdeletion were inherited maternally. Of the CNVs of uncertain significance, there were two 16p13.11 microduplications, each inherited from a different parent, one paternally and one maternally; meanwhile, family validation was refused in the other three cases with 3p22.1 microdeletion, 3p26.3 microdeletion, and 9q21.33q22.31 microduplication. The detection rate of pathogenic CNVs in the moderate IVM group was higher than that in the mild IVM group [6.3% (3/48) vs. 1.2% (2/167)], but the difference was not statistically significant ( P=0.083). Similarly, no significant difference was found in the detection rate of pathogenic CNVs when comparing the unilateral IVM group [2.1% (3/142)] with the bilateral IVM group [2.7% (2/73)], nor between the group diagnosed with VM before 28 weeks gestation [2.2% (3/138)] and that diagnosed ≥28 weeks [2.6% (2/77)] (both P>0.05). After the exclusion of fetuses with chromosomal pathogenic abnormalities ( n=11), cytomegalovirus infection( n=1), and additional ultrasound anomalies ( n=7), and several cases with missing data intrauterine outcomes were followed up in 169 IVM fetuses, including 104 (61.5%) improved, 60 (35.5%) unchanged, and five (3.0%) progressed. Follow-ups were successful for 194 women, of which eight pregnancies were terminated (including one trisomy 21, four pathogenic CNVs, one fetal cytomegalovirus infection, and two progressed to severe IVM). Among the 186 newborns, one was diagnosed with X-linked ichthyosis, and one child who progressed to severe IVM before born was followed until 20 months of age without notable phenotypic abnormalities. The rest 184 babies, including those with CNVs of uncertain clinical significance, exhibited no developmental abnormalities during follow-up between the ages of three months and six years. Conclusions:For those fetuses with isolated mild to moderate IVM, but without indications for prenatal diagnosis such as advanced maternal age, high risk in serum screening or abnormal history of pregnancy, remain having the risk for chromosomal aberrations, and 16p11.2 microdeletion/microduplication might be a frequent CNV associated with this condition. Aside from those with pathogenic chromosomal aberrations, fetal cytomegalovirus infection, or progressive enlargement of the lateral ventricles, most fetuses with isolated mild to moderate IVM have a good prognosis.

Purpose: This study examined the diagnostic value of high-frequency ultrasound (HFUS) features in differentiating between benign and malignant skin lesions. Methods: A total of 1,392 patients with 1,422 skin lesions who underwent HFUS examinations were included in an initial dataset (cohort 1) to identify features indicative of malignancy. Qualitative clinical and HFUS characteristics were recorded for all lesions. To determine which HFUS and clinical features were suggestive of malignancy, univariable and multivariable logistic regression analyses were employed. The diagnostic performance of HFUS features combined with clinical information was evaluated. This assessment was validated using internal data (cohort 2) and multicenter external data (cohort 3). Results: Features significantly associated with malignancy included age above 60 years; lesion location in the head, face, and neck or genital regions; changes in macroscopic appearance; crawling or irregular growth pattern; convex or irregular base; punctate hyperechogenicity; blood flow signals; and feeding arteries. The area under the receiver operating characteristic curve, sensitivity, and specificity of HFUS features combined with clinical information were 0.946, 92.5%, and 86.9% in cohort 1; 0.870, 93.1%, and 80.8% in cohort 2 (610 lesions); and 0.864, 86.2%, and 86.6% in cohort 3 (170 lesions), respectively. However, HFUS is not suitable for evaluating lesions less than 0.1 mm in thickness or lesions exhibiting surface hyperkeratosis. Conclusion In a clinical setting, the integration of HFUS with clinical information exhibited good diagnostic performance in differentiating malignant and benign skin lesions. However, its utility was limited in evaluating extremely thin lesions and those exhibiting hyperkeratosis.

Purpose: This study examined the diagnostic value of high-frequency ultrasound (HFUS) features in differentiating between benign and malignant skin lesions. Methods: A total of 1,392 patients with 1,422 skin lesions who underwent HFUS examinations were included in an initial dataset (cohort 1) to identify features indicative of malignancy. Qualitative clinical and HFUS characteristics were recorded for all lesions. To determine which HFUS and clinical features were suggestive of malignancy, univariable and multivariable logistic regression analyses were employed. The diagnostic performance of HFUS features combined with clinical information was evaluated. This assessment was validated using internal data (cohort 2) and multicenter external data (cohort 3). Results: Features significantly associated with malignancy included age above 60 years; lesion location in the head, face, and neck or genital regions; changes in macroscopic appearance; crawling or irregular growth pattern; convex or irregular base; punctate hyperechogenicity; blood flow signals; and feeding arteries. The area under the receiver operating characteristic curve, sensitivity, and specificity of HFUS features combined with clinical information were 0.946, 92.5%, and 86.9% in cohort 1; 0.870, 93.1%, and 80.8% in cohort 2 (610 lesions); and 0.864, 86.2%, and 86.6% in cohort 3 (170 lesions), respectively. However, HFUS is not suitable for evaluating lesions less than 0.1 mm in thickness or lesions exhibiting surface hyperkeratosis. Conclusion In a clinical setting, the integration of HFUS with clinical information exhibited good diagnostic performance in differentiating malignant and benign skin lesions. However, its utility was limited in evaluating extremely thin lesions and those exhibiting hyperkeratosis.

Purpose: This study examined the diagnostic value of high-frequency ultrasound (HFUS) features in differentiating between benign and malignant skin lesions. Methods: A total of 1,392 patients with 1,422 skin lesions who underwent HFUS examinations were included in an initial dataset (cohort 1) to identify features indicative of malignancy. Qualitative clinical and HFUS characteristics were recorded for all lesions. To determine which HFUS and clinical features were suggestive of malignancy, univariable and multivariable logistic regression analyses were employed. The diagnostic performance of HFUS features combined with clinical information was evaluated. This assessment was validated using internal data (cohort 2) and multicenter external data (cohort 3). Results: Features significantly associated with malignancy included age above 60 years; lesion location in the head, face, and neck or genital regions; changes in macroscopic appearance; crawling or irregular growth pattern; convex or irregular base; punctate hyperechogenicity; blood flow signals; and feeding arteries. The area under the receiver operating characteristic curve, sensitivity, and specificity of HFUS features combined with clinical information were 0.946, 92.5%, and 86.9% in cohort 1; 0.870, 93.1%, and 80.8% in cohort 2 (610 lesions); and 0.864, 86.2%, and 86.6% in cohort 3 (170 lesions), respectively. However, HFUS is not suitable for evaluating lesions less than 0.1 mm in thickness or lesions exhibiting surface hyperkeratosis. Conclusion In a clinical setting, the integration of HFUS with clinical information exhibited good diagnostic performance in differentiating malignant and benign skin lesions. However, its utility was limited in evaluating extremely thin lesions and those exhibiting hyperkeratosis.