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 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 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 investigate the application value of antegrade splenic superior region dissection first in laparoscopic total gastrectomy of obesity gastric cancer.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 21 obesity patients with gastric cancer who underwent laparoscopic total gastrectomy in Renji Hospital of Shanghai Jiaotong University School of Medicine from July 2018 to October 2023 were collected. There were 16 males and 5 females, aged (58±13)years. All 21 patients underwent laparoscopic total gastrec-tomy with antegrade splenic superior region dissection first. Observation indicators: operation time, volume of intraoperative blood loss, laparotomy conversion, intraoperative splenic hemorrhage or gastric hemorrhage, lymph node dissection, time to postoperative first flatus, time to postoperative initial liquid food intake, duration of postoperative hospital stay, postoperative complication. Measure-ment data with normal distribution were represented as Mean± SD, and count data were expressed as absolute numbers. Results:All 21 patients underwent laparoscopic total gastrectomy success-fully, with the operation time of (283±47)minutes, time for splenogastric ligament and vascular manage-ment of (34±12)minutes, volume of intraoperative blood loss of (143±86)mL, and no laparotomy conversion. There was no intraoperative splenic hemorrhage or gastric haemorrhage. The total number of lymph node dissected in 21 patients was 375, with the number of lymph node dissected as (21±9)per case. Time to postoperative first flatus, time to postoperative initial liquid food intake and duration of postoperative hospital stay in 21 patients were (3.1±0.7)days, (4.0±0.8)days and (10.1±3.0)days, respectively. There were 2 patients with postoperative complications, including 1 case of incision infection and 1 case of lung infection. The 2 patients with postoperative com-plications were recovered and discharged after conservative treatment. There was no death during the postoperative 30 days.Conclusion:The application of antegrade splenic superior region dissec-tion first in laparoscopic total gastrectomy is safe and feasible, which can reduce surgical difficulty.

Objective:To explore the real work experience and needs of nursing assistants of elderly patients with disability and mental disorders, and provide reference for relevant institutions to develop a reasonable support system and promote their physical and mental health.Methods:From October to November 2022, purposive sampling was used to select nursing assistants of elderly patients with disability and mental disorders from the Affiliated Brain Hospital of Guangzhou Medical University as the research subject. The phenomenological method was used to conduct in-depth interviews, recordings, and transcripts of 12 nursing assistants. The Colaizzi analysis program was used to analyze, organize, refine, and summarize.Results:A total of five themes were extracted, including multiple emotional experiences, lack of rest and relaxation, insufficient professional identity and external support, lack of care knowledge and skills, heavy workload and poor treatment.Conclusions:Accompanying management institutions and hospitals need to strengthen their attention to nursing assistants, reduce their physical and mental burden, attach importance to skill training, increase welfare benefits, enhance professional identity, and improve the quality of care.

Objective:To summarize the best evidence for exercise intervention in elderly patients with sarcopenia in intensive care unit (ICU) through literature search, and provide a reference for clinical implementation of early exercise intervention in this population through evidence-based practice.Methods:① Summary of best evidence: relevant literature on exercise intervention for elderly patients with sarcopenia in ICU, including guideline, evidence summary, expert consensus, systematic review, and original study [quasi-experiment and randomized controlled trial (RCT)] from UpToDate Clinical Advisor, Ovid database, National Guideline Clearinghouse (NGC), National Institute for Health and Care Excellence (NICE), Cochrane Library, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed/Medline, SinoMed, CNKI, Wanfang Database, VIP, and Yimai Tong Guideline Network were systematically searched. The search period covered from the establishment of these databases up to August 24, 2023. The quality of the literature was evaluated by two researchers with methodological expertise in evidence-based medicine, and the evidences were extracted and summarized. ② Evidence-based practice: the elderly patients with high risk of sarcopenia who had been hospitalized in the ICU for more than 7 days from January to April 2024 were enrolled as the research subjects, and they were divided into a control group and an intervention group using convenience sampling method. The control group received routine intensive care nursing. The intervention group implemented exercise intervention based on the actual situation of the patients, the baseline review was conducted before evidence application, and the effectiveness of evidence application at 7 days and 14 days was evaluated.Results:① A total of 19 pieces of literature were included, including 4 guidelines, 1 summary of evidence, 4 expert consensuses, 4 systematic reviews, and 6 original studies (1 quasi-experiment, 5 RCT). After literature quality evaluation, all 19 articles were enrolled. Finally, 31 pieces of best evidence were extracted from eight aspects, including assessment and diagnosis, multidisciplinary cooperation, indication, preparation before intervention, intervention program, safety monitoring, post-intervention evaluation, and special task. ② Finally, a total of 30 patients were enrolled in the intervention group, of which 17 completed 14 days of rehabilitation exercise, and 13 completed 7 days of rehabilitation exercise. Twenty-seven patients were enrolled in the control group, of which 17 completed 14 days of monitoring, and 10 completed 7 days of monitoring. Clinical evidence application results showed that the patients in the intervention group did not experience adverse events such as increased heart rate, extubation, or physical discomfort. The skeletal muscle mass index (SMI) in both groups was gradually decreased with the prolongation of intervention duration, but the 7-day SMI in the intervention group was significantly higher than that in the control group (kg/m 2: 8.61±2.66 vs. 6.65±1.50, P < 0.01). Conclusion:By summarizing the best evidence and evidence-based practice of exercise intervention for elderly patients with sarcopenia in ICU, this study confirmed the feasibility due to safe and effective of implementing early exercise intervention for elderly sarcopenia patients in ICU.

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.