1.Expression and Clinical Significance of Nucleoporin 93 in Patients with Neuroblastoma
Minting LIANG ; Yang YANG ; Xiaojun LIU ; Huiya LIANG ; Hanyi ZHANG ; Yihan SUN ; Xiuyu SHI ; Xia YANG
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(3):420-430
ObjectiveTo screen key genes associated with neuroblastoma (NB) diagnosis and prognosis using the Gene Expression Omnibus (GEO) database, and to investigate the expression and clinical significance of nucleoporin 93 (NUP93) in NB tissues. MethodsNB gene chip data (GSE73517, GSE49710, GSE19274) were retrieved from the GEO database. Differentially expressed genes (DEGs) commonly upregulated in high-risk groups were screened. The R2 database was then used to assess the prognostic value of DEGs that were commonly upregulated in the MYCN amplification group. Finally, NUP93 expression levels in the tissues from 60 NB, 25 ganglioneuroblastoma (GNB), and 26 ganglioneuroma (GN) cases were measured by immunohistochemistry . ResultsTwenty-five DEGs were identified as commonly upregulated in high-risk groups. Among these, 10 genes (SIVA1, NUP93, STIP1, LSM4, RAI14, MYOZ3, KNTC1, TNFRSF10B, TACC3 and CEP152) showed significantly higher expression in MYCN-amplified subgroups (P<0.05). Survival analysis revealed that high NUP93 expression was associated with shorter overall survival (HR = 4.0, 95% CI: 3.0,5.3, P = 1.80 × 10⁻³⁴). Immunohistochemistry results revealed that NUP93 expression in NB tissues was significantly higher than in GNB and GN tissues (P<0.001). NUP93 expression was positively correlated with high mitosis-karyorrhexis index (MKI; P=0.040), poor differentiation (P<0.001), and MYCN expression (rs = 0.793, P <0.001). ConclusionsHigh expression of NUP93 is associated with high MKI and poor differentiation, and predicts unfavorable prognosis in patients with NB, suggesting it may promote tumor progression by regulating MYCN. NUP93 has the potential to be a novel diagnostic biomarker and therapeutic target for NB.
2.Untargeted Metabolomics Analysis of Demyelination in the Brain of Balb/c Mice Infected by Angiostrongylus cantonensis
Zhen NIU ; Xiaojie WU ; Liang YANG ; Zhixuan MA ; Junxiong YANG ; Ying FENG
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(2):293-300
ObjectiveTo investigate the demyelination induced by Angiostrongylus cantonensis (AC) infection in the brain of Balb/c mice and analyze the untargeted metabolomic changes in the corpus callosum, aiming to elucidate the underlying mechanisms. MethodsBalb/c mice were randomly assigned to a control group (n=6) and an infection group (n=6). The infection group was orally administered 30 third-stage larvae of AC, while the control group received an equal volume of saline. Body weight, visual function, and behavioral scores were measured on post-infection 3, 6, 9, 12, 15, 18, and 21 days to assess neurological alterations. After 21 days, brain tissues were harvested for immunofluorescence staining, hematoxylin-eosin (HE) staining, and transmission electron microscopy to examine morphological changes in brain myelin and retina. Metabolomics analysis was performed, and differential metabolites were identified using volcano plots and heatmaps. The distribution of fold changes and bar charts were used to profile the key metabolites. These differential metabolites were then subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and regulatory network analysis. ResultsOn the 9th day after AC infection, Balb/c mice showed a decline in neurological behavioral scores (P<0.05). By day 15, visual scores decreased (P<0.05), and by day 21, significant weight loss (P<0.001) and mortality were observed. Concurrently, transmission electron microscopy and immunofluorescence staining revealed significant myelin damage in the corpus callosum and a marked reduction in oligodendrocytes (P<0.001). HE staining showed severe retinal ganglion cell damage. Metabolomic analysis revealed that glycerophospholipids were the most abundant differential metabolites, with steroids and sphingolipids being relatively less abundant. Cholesteryl ester CE (20:2) was significantly upregulated (P<0.001), while phosphatidylmethanol (18:0_18:1) was significantly downregulated (P<0.01). KEGG enrichment and regulatory network analyses demonstrated that the differential metabolites were mainly enriched in metabolic pathways like steroid biosynthesis, bile secretion, and cholesterol metabolism, and were involved in key metabolic pathways such as sphingolipid metabolism, neural signal regulation, and glycerophospholipid metabolism. ConclusionsAC infection affects the metabolic state of mice via multiple pathways, modifying the levels of metabolites crucial for myelination and myelin stability. Demyelination may be closely linked to the disruption of these key metabolic pathways, particularly the dysregulation of cholesterol and sphingolipid metabolism, potentially playing a central role in demyelination onset. Furthermore, alterations in phospholipid metabolism and abnormal nerve signaling regulation may exacerbate myelin damage.
3.Predicting Hepatocellular Carcinoma Using Brightness Change Curves Derived From Contrast-enhanced Ultrasound Images
Ying-Ying CHEN ; Shang-Lin JIANG ; Liang-Hui HUANG ; Ya-Guang ZENG ; Xue-Hua WANG ; Wei ZHENG
Progress in Biochemistry and Biophysics 2025;52(8):2163-2172
ObjectivePrimary liver cancer, predominantly hepatocellular carcinoma (HCC), is a significant global health issue, ranking as the sixth most diagnosed cancer and the third leading cause of cancer-related mortality. Accurate and early diagnosis of HCC is crucial for effective treatment, as HCC and non-HCC malignancies like intrahepatic cholangiocarcinoma (ICC) exhibit different prognoses and treatment responses. Traditional diagnostic methods, including liver biopsy and contrast-enhanced ultrasound (CEUS), face limitations in applicability and objectivity. The primary objective of this study was to develop an advanced, light-weighted classification network capable of distinguishing HCC from other non-HCC malignancies by leveraging the automatic analysis of brightness changes in CEUS images. The ultimate goal was to create a user-friendly and cost-efficient computer-aided diagnostic tool that could assist radiologists in making more accurate and efficient clinical decisions. MethodsThis retrospective study encompassed a total of 161 patients, comprising 131 diagnosed with HCC and 30 with non-HCC malignancies. To achieve accurate tumor detection, the YOLOX network was employed to identify the region of interest (ROI) on both B-mode ultrasound and CEUS images. A custom-developed algorithm was then utilized to extract brightness change curves from the tumor and adjacent liver parenchyma regions within the CEUS images. These curves provided critical data for the subsequent analysis and classification process. To analyze the extracted brightness change curves and classify the malignancies, we developed and compared several models. These included one-dimensional convolutional neural networks (1D-ResNet, 1D-ConvNeXt, and 1D-CNN), as well as traditional machine-learning methods such as support vector machine (SVM), ensemble learning (EL), k-nearest neighbor (KNN), and decision tree (DT). The diagnostic performance of each method in distinguishing HCC from non-HCC malignancies was rigorously evaluated using four key metrics: area under the receiver operating characteristic (AUC), accuracy (ACC), sensitivity (SE), and specificity (SP). ResultsThe evaluation of the machine-learning methods revealed AUC values of 0.70 for SVM, 0.56 for ensemble learning, 0.63 for KNN, and 0.72 for the decision tree. These results indicated moderate to fair performance in classifying the malignancies based on the brightness change curves. In contrast, the deep learning models demonstrated significantly higher AUCs, with 1D-ResNet achieving an AUC of 0.72, 1D-ConvNeXt reaching 0.82, and 1D-CNN obtaining the highest AUC of 0.84. Moreover, under the five-fold cross-validation scheme, the 1D-CNN model outperformed other models in both accuracy and specificity. Specifically, it achieved accuracy improvements of 3.8% to 10.0% and specificity enhancements of 6.6% to 43.3% over competing approaches. The superior performance of the 1D-CNN model highlighted its potential as a powerful tool for accurate classification. ConclusionThe 1D-CNN model proved to be the most effective in differentiating HCC from non-HCC malignancies, surpassing both traditional machine-learning methods and other deep learning models. This study successfully developed a user-friendly and cost-efficient computer-aided diagnostic solution that would significantly enhances radiologists’ diagnostic capabilities. By improving the accuracy and efficiency of clinical decision-making, this tool has the potential to positively impact patient care and outcomes. Future work may focus on further refining the model and exploring its integration with multimodal ultrasound data to maximize its accuracy and applicability.
4.Consensus on low-altitude transport and delivery services for emergency medicines via drones (2025 edition)
Qinshui WU ; Yanfang CHEN ; Tao LIU ; Xiaoyan LI ; Yumin LIANG ; Xin LI ; Zhong LI ; Rong LI ; Xiaoman WANG ; Shuyao ZHANG ; Huishu TIAN
China Pharmacy 2025;36(18):2221-2225
OBJECTIVE To promote the application of drones in emergency rescue and related fields, expand “low-altitude+ medical” rescue services, and advance the standardization of “low-altitude+medical” distribution services. METHODS The Consensus on Low-altitude Transport and Delivery Services for Emergency Medicines via Drones (2025 Edition) (hereinafter referred to as the Consensus) was jointly initiated by the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society and the Expert Committee on Precision Medication of the Guangdong Pharmaceutical Association. Guangzhou Red Cross Hospital served as the leading unit, organizing 53 multidisciplinary experts nationwide to participate in drafting and reviewing. A nominal group technique was employed to discuss and finalize the consensus outline, resulting in a preliminary draft. Delphi method was employed, and 11 external review experts were invited to conduct the evaluation. After the experts’ opinions were analyzed and integrated, the Consensus was finalized. RESULTS & CONCLUSIONS The finalized Consensus includes its purpose, principles, and applicable scenarios, basic requirements, and operational procedures for low-altitude transport and delivery of emergency medications; distribution requirements and precautions for controlled substances, fragile medications, and temperature-sensitive medications; and recommendations for emergency medications supplies suitable for the low-altitude transportation and distribution. The release of this Consensus is expected to provide guidance and support for the standardization of “low-altitude+medical” distribution services and the application of low-altitude economy in the healthcare sector.
5.Association between the Non-Fasting Triglyceride-Glucose Index and Hyperglycemia in pregnancy during the Third Trimester in High Altitudes
Qingqing WANG ; Hongying HOU ; Ma NI ; Yating LIANG ; Xiaoyu CHEN ; WA Zhuoga DA ; Qiang LIU ; Zhenyan HAN
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(5):861-871
ObjectiveTo investigate the relationship between the non-fasting triglyceride and glucose (TyG) index and hyperglycemia in pregnancy during the third trimester in high altitudes. MethodsThis study selected clinical and laboratory data of 774 Tibetan singleton pregnant women who delivered at Chaya People's Hospital of Qamdo city in Xizang autonomous region, from January 2023 to April 2025. The non-fasting TyG index was calculated from non-fasting triglyceride (TG) and random plasma glucose (PG). Based on the tertiles of the non-fasting TyG index values, the individuals were split into three groups (corresponding to non-fasting TyG index of 8.89 and 9.21, respectively). The baseline clinical characteristics, lipid levels and the occurrence of developing hyperglycemia in pregnancy were compared among the three groups. Statistical analyses were performed using ANOVA, Kruskal-Wallis H test, Chi-square test, or Fisher exact test and the relationship between the non-fasting TyG index and hyperglycemia in pregnancy were examined using multivariate logistic regression models and curve fitting. ResultsA total of 774 Tibetan singleton pregnant women were included, with a average age of 27.3 ± 6.1 years, a pre-delivery body mass index (Pre-BMI) of (25.2±2.3)kg/m2 , a proportion of 26.7% (207/774) primigravid women, the mean non-fasting TyG index was 9.1 ± 0.4。Thirty pregnant women were diagnosed with hyperglycemia in pregnancy, with a detection rate of 3.9% (30/774). Statistically significant differences in serum total cholesterol (TC), TG, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were identified when comparing different non-fasting TyG groups (all P values <0.05). Subsequent trend test analysis indicated that the levels of TC, TG, LDL-C, and PG gradually increased with elevated the non-fasting TyG index ( Ftrend TC=95.61, P<0.001; Ftrend TG=1 051.91, P<0.001; Ftrend LDL-C = 97.20, P < 0.001; Ftrend TG=195.20; P<0.001). After adjustment for maternal age, pre-delivery BMI, altitude, TC, LDL-C, and HDL-C, multivariate Logistic regression models revealed independent positive associations between non-fasting TyG index and hyperglycemia in pregnancy (Model 1: OR=2.72, 95% CI: 1.13-6.53, P=0.026; Model 2: OR=2.56, 95% CI: 1.01-6.50, P=0.048; Model 3: OR=2.72, 95% CI: 1.06-6.97, P=0.037; Model 4: OR=4.02, 95% CI: 1.42-11.40, P=0.009) and the incident of hyperglycemia in pregnancy showed an increasing tendency as increasing with the non-fasting TyG index, however, this association did not statistical significance (P trend >0.05). Curve fitting by restricted cubic splines (RCS) were used to assess linearity between non-fasting TyG and hyperglycemia in pregnancy, and there was a linear dose-response relationship between non-fasting TyG and hyperglycemia in pregnancy (P for non-linear = 0.515). ConclusionNon-fasting TyG index in the third trimester is a risk factor for hyperglycemia in pregnancy among the Tibetan singleton pregnant women at high altitudes and there was a possible linear dose-response relationship between the non-fasting TyG index and hyperglycemia in pregnancy.
6.Clinical and Genetic Study on 48 Children with Short Stature of Unknown Etiology
Lele HOU ; Shaofen LIN ; Xiaojuan LI ; Zulin LIU ; Hui OU ; Lina ZHANG ; Zhe MENG ; Liyang LIANG
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(1):127-135
ObjectiveTo explore the clinical features and causative genes of short stature children with unknown etiology, providing evidence for precise clinical diagnosis and treatment. MethodsThe study recruited children with suspected but undiagnosed short stature from the pediatric endocrinology department in our hospital between January 2018 and August 2022. A retrospective analysis was performed on the clinical manifestations, laboratory test and whole exome sequencing (WES) results. Causative genes were classified and analyzed according to different pathogenic mechanisms. ResultsA total of 48 children (30 boys and 18 girls) were enrolled, aged 7.73 ± 3.97 years, with a height standard deviation score ( HtSDS) of -3.63 ± 1.67. Of the patients, 33 (68.8%) suffered from facial anomalies, 31 (64.6%) from skeletal abnormalities, 26 [54.2%, 61.5% of whom born small for gestational age (SGA)] from perinatal abnormalities, 24 [50.0%, 87.5% of whom with growth hormone (GH) peak concentration below normal] from endocrine disorders and 21(43.8%) had a family history of short stature. Laboratory tests showed that GH peak concentration following stimulation test was (9.72 ± 7.25) ng/mL, IGF-1 standard deviation score was -0.82 ± 1.42, the difference between bone age and chronological age was -0.93 ± 1.39 years. Of the 25 cases with mutant genes found by WES, 14 (56.0%) had pathogenic mutation, 6 (24.0%) likely pathogenic mutation, and 5 (20.0%) mutation of uncertain significance. Pathogenic and likely pathogenic variants were identified in 14 genes, including 10 affecting intracellular signaling pathways (PTPN11, RAF1, RIT1, ARID1B, ANKRD11, CSNK2A1, SRCAP, CUL7, SMAD4 and FAM111A) and 4 affecting extracellular matrix (ECM) components or functions (ACAN, FBN1, COL10A1 and COMP). ConclusionsA rare monogenic disease should be considered as the possible etiology for children with severe short stature accompanied by facial anomalies, disproportionate body types, skeletal abnormalities, SGA, GH peak concentration below normal and a family history of short stature. WES played an important role in identifying the monogenic causes of short stature. This study indicated that affecting growth plate cartilage formation through intracellular signaling pathways and ECM components or functions was the main mechanism of causative genes leading to severe short stature in children. Further research may help discover and study new pathogenic variants and gene functions.
7.Protective role and mechanistic exploration of Irisin in doxorubicin induced-cardiomyopathy
Yu-Ge JIN ; Song-Sen LI ; Hao WANG ; Cai-Ru GUO ; Bing-Bing ZHANG ; Hao-Jie CHEN ; Ya-Xin BAN ; Ru-Bing LIANG
The Chinese Journal of Clinical Pharmacology 2024;40(2):220-224
Objective To study the protective effect of Irisin in doxorubicin(Dox)induced-Cardiomyopathy and its possible mechanism.Methods AC 16 cells were used to construct Dox injury model and divided into control group(AC 16 cells were cultured with complete medium),Irisin group(AC16 cells were treated with 10 ng·L-1 Irisin for 24 h),Dox group(AC 16 cells were treated with 4 μmol·L-1 Dox for 24 h),Dox+Irisin group(AC 16 cells were pretreated with 10 ng·L-1 Irisin for 2 h,and then treated with 4 pmol·L-1 Dox for 24 h).Cell counting kit-8(CCK-8),terminal deoxynucleotidyl transferase-mediated nick end labeling(TUNEL)and lactate dehydrogenase(LDH)were used to detect the proliferation,apoptosis and mortality of AC 16 cells.Western blot was used to detect the expression levels of nuclear factor-κB(NF-κB)signaling pathway and apoptotic factors B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax)and caspase-9 protein.Mito-Tracker Red CMXRos probe was used to detect mitochondrial membrane potential.Results In the contrl group,Irisin group,Dox group,Dox+Irisin group,the rate of apoptosis were(0.97±0.09)%,0,(42.80±6.70)%,(11.74±1.79)%;the expression of Bax protein were 0.85±0.01,0.36±0.02,1.15±0.07,0.37±0.11;the expression of caspase-9 protein were 0.52±0.02,0.59±0.03,1.11±0.02,0.67±0.08;the expression of Bcl-2 protein were 1.01±0.04,1.05±0.25,0.43±0.02 and 0.99±0.30;the probability of mitochondrial damage were(0.02±0.01)%,(0.5±0.15)%,(38.6±2.39)%,(1.58±0.54)%.The difference of the above indexes between the contrl group and the Dox group were statistically significant(all P<0.05);the difference between Dox group and Dox+Irisin group were statisically significant(all P<0.05).Conclusion Irisin could reduce the expression level of Bax,caspase-9,p-NF-κB,and p-mTOR caused by Dox,increase the expression level of Bcl-2,ameliorate the myocardial damage caused by Dox,and reduce cardiotoxicity.
8.Subdiaphragmatic abscess caused by the recently identified pathogen Cutibacterium modestum: a case report
World Journal of Emergency Medicine 2024;15(5):422-424
Subdiaphragmatic abscess is uncommon in patients who undergo resection for hepatocellular carcinoma. The identification of pathogens and appropriate treatment can be challenging.[1] Herein, we present a case of subdiaphragmatic abscess caused by Cutibacterium modestum.
9.Low BMI is Associated with Poor OI-IUI Outcomes in Patients with Unexplained Primary Infertility
Yihua LIANG ; Xuedan JIAO ; Qingxue ZHANG ; Hui CHEN ; Yu LI
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(2):283-289
ObjectiveTo evaluate the effect of women's body mass index (BMI) on pregnancy outcomes of ovulation induction intrauterine insemination (OI-IUI) in patients with unexplained primary infertility. MethodsThe study included 764 OI-IUI cycles from January 2016 to December 2022 in reproductive center of Sun Yat-sen Memorial Hospital. According to BMI,patients were divided into three groups:low BMI (BMI<18.5 kg/m2), normal BMI (18.5 kg/m2 ≤BMI<23.0 kg/m2), and high BMI (BMI≥23.0 kg/m2). Comparison of clinical data and pregnancy outcomes was performed between the groups. Logistic regression was used to analyze the association between BMI and live birth rate. ResultsFrom the low BMI group to the high BMI group, the HCG positive rate (7.08%,9.74%, 13.19%), clinical pregnancy rate(5.51%, 7.91%, 13.19%), and live birth rate (4.72%, 6.90%, 12.50%) increased. Among them, the live birth rate of the high BMI group was significantly higher than that of the low BMI group and the normal BMI group, with a statistically significant difference (P=0.034). While the early miscarriage rate (14.28%, 10.26%, 5.26%) decreased from the low BMI group to the high BMI group. The binary logistic regression analysis revealed that BMI was an independent factor in live birth, and high BMI resulted in a better live birth rate than low BMI (OR=3.15,95%CI=1.191-8.329,P=0.021). ConclusionLow BMI is associated with poor OI-IUI outcomes in patients with unexplained primary infertility. These patients are encouraged to gain weight in a healthy manner.
10.Feasibility of a novel type of complex anterior cervical fixation by using Mimics software
Zhi-Peng HOU ; Sen-Qi YE ; Ji-Hui ZHANG ; Liu-Jun ZHAO ; Yong-Jie GU ; Liang YU
China Journal of Orthopaedics and Traumatology 2024;37(1):81-85
Objective To investigate the feasibility of mimics software in analyzing a new type of complex anterior cervical fixation—anterior transpedicular screw fixation+zero notch internal fixation.Methods From January 2021 to September 2022,50 normal pedestrians who underwent cervical spine CT scanning were selected for C1-C7 segment scanning,including 27 males and 23 females,aged from 25 to 65 years old with an average of(46.0±9.0)years old.The dicom format is exported and engraved into the CD,and use the mimics software to perform 3D reconstruction of each segment.A simulated screw is placed on the image according to the critical value of zero notch screw(head and tail angle 44°,internal angle 29°).The posi-tion of zero notch screw in each segment is observed to determine the feasibility of anterior transpedicular screw fixation plus zero notch internal fixation.Results For the upper zero notch screws the three-dimensional images of the cervical spine across all 50 subjects within the C3-C7 segments demonstrated safe position,wwith no instances of intersection with ATPS.For the lower zero notch screw,in C3-C4 and C4-C5,4 out of 50 subjects are in the safe position in the three-dimensional images of cervical ver-tebrae,and 46 cases could achieve secure screw placement when the maximum caudal angle is(32.3±1.9)° and(36.1±2.2)°,respectively.In C5-C6 and C6-C7 segments,no lower zero notch screws intersected with ATPS,and all screws are in safe posi-tions.Conclusion Lower cervical anterior pedicle screw fixation plus zero notch internal fixation can achieve successful nail placement through the selected entry point and position.


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