1.Qiangjing Tablets Regulate CDK4-E2F Signaling Pathway to Delay Aging of Leydig Cells and Testicular Tissue in Rats
Xiucheng LAN ; Meijing WANG ; Jingyi ZHANG ; Junjun LI ; Liang DONG ; Xujun YU ; Fang YANG ; Degui CHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):328-336
ObjectiveTo reveal the molecular mechanism by which the traditional Chinese medicine compound prescription Qiangjing tablets regulate the aging of the testicular tissue and Leydig cells in rats through the cyclin-dependent kinase 4 (CDK4)-early 2 factor (E2F) signaling pathway. MethodsFor the cell experiment, 2-month-old SPF-grade SD male rats were selected and randomly assigned into a blank control group (administrated with an equal volume of 0.9% sodium chloride injection) and a Qiangjing tablets group (20 rats in each group) according to body weight. The Leydig cell model of aging was established by treatment of TM3 cells with 100 μmol·L-1 H2O2, and the modeling performance was evaluated based on the levels of p16 and p21 determined by Western blot. The antioxidant NAC (1 mmol·L-1) was used as the positive control for eliminating reactive oxygen species (ROS). Cells were intervened with Qiangjing tablets-containing serum at low (2.5%), medium (5%), and high (10%) concentrations. The testosterone level in the cell supernatant was determined by enzyme-linked immunosorbent assay (ELISA), and the protein levels of CDK4, E2F1, and E2F2 were analyzed by Western blot. In the animal experiment, 19-month-old naturally aging rats were used as the model group, and 2-month-old rats as the young control group. The positive control group was subcutaneously injected with 5.21 mg·kg-1·d-1 testosterone propionate. Qiangjing tablets were administered by gavage at low, medium, and high doses of 0.72, 1.44, 2.88 g·kg-1·d-1, respectively. The general conditions of rats were observed, and the protein levels of CDK4, E2F1, and E2F2 in the testicular tissue were determined by Western blot. ResultsIn the cell experiment, compared with the blank control group, the model group showed upregulated expression of CDK4 and E2F1 (P<0.05) and slightly downregulated expression of E2F2. Compared with that in the model group, the expression of CDK4 was upregulated in the NAC group and the low-dose Qiangjing tablets group (P<0.05), slightly upregulated in the medium-dose Qiangjing tablets group, and downregulated in the high-dose Qiangjing tablets group (P<0.05). The NAC group showed downregulated expression of E2F1 (P<0.05) and E2F2, and the low-, medium-, and high-dose Qiangjing tablets groups showed downregulated expression of both E2F1 and E2F2 (P<0.05). Compared with that in the NAC group, the expression of CDK4 was upregulated in the low-dose Qiangjing tablets group and downregulated in the medium-dose and high dose (P<0.05) groups. The expression of E2F1 was down-regulated in all the three dose groups, with statistically significance in the high dose group (P<0.05), and that of E2F2 were downregulated in all the three dose groups (P<0.05). In the animal experiment, compared with the young control group, the model group exhibited downregulated expression of CDK4 (P<0.05) and slightly upregulated expression of E2F1 and E2F2. Compared with that in the model group, the expression of CDK4 decreased in the testosterone propionate group and the low-dose Qiangjing tablets group (P<0.05) but increased in the medium-dose (P<0.05) and high-dose groups. In addition, the expression of E2F1 decreased (P<0.05), and that of E2F2 was slightly elevated. Compared with that in the NAC group, CDK4 expression was elevated in the Qiangjing tablets groups, with statistical significance in the medium- and high-dose groups (P<0.05). Similarly, the E2F1 expression was also upregulated in the Qiangjing tablets groups, with statistical significance in the medium-dose group (P<0.05). The expression of E2F2 was downregulated in all the Qiangjing tablets groups. ConclusionQiangjing tablets delay the aging process of Leydig cells and testicular tissue by up-regulating the expression of CDK4 and lowering the levels of E2F1 and E2F2.
2.Mechanism of Quercetin-loaded Exosomes in Improving Testosterone Synthesis in Leydig Cells from Correlation Perspective of "Disease, Syndrome, Formula, and Medicine"
Meijing WANG ; Xiucheng LAN ; Fangyue WANG ; Jingyi ZHANG ; Guangsen LI ; Degui CHANG ; Xujun YU ; Fang YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):360-370
ObjectiveBased on the multidimensional correlation analysis framework of "disease, syndrome, formula, and medicine", this study aims to systematically elucidate the regulatory effects of effective components in Qiangjing tablet on testosterone synthesis pathways in testicular Leydig cells under oxidative stress, providing a theoretical basis for the treatment of male infertility with traditional Chinese medicine and modern research on compounds. MethodsDisease targets for male infertility were obtained from The Human Gene Database (GeneCards, score ≥20), the Comparative Toxicogenomics Database (CTD, score ≥150), DrugBank (score ≥0.2), and DisGeNET (score ≥0.2). Targets related to the syndrome of kidney deficiency and blood stasis were acquired from the traditional Chinese medicine syndrome association database SymMap. Components of Qiangjing tablet were retrieved based on The Encyclopedia of Traditional Chinese Medicine (ETCM) database and the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP), and they were screened according to a quantitative estimate of drug-likeness (QED ≥ 0.49) and a target confidence index>0.8. Intersecting targets were taken to construct a protein-protein interaction (PPI) network using the STRING database. The network was visualized with Cytoscape software and subjected to the functional annotation of gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. Quality markers (Q-markers) were predicted via the ADMETlab 2.0 platform based on Lipinski's rule, Pfizer's rule, GSK's rule, and the Golden Triangle. For experimental validation, rats' testicular Leydig cells were used. Exosomes were extracted and loaded with active components via the ultrasonic method. Exosome concentration was determined using a BCA protein quantification kit. Morphology was observed using a transmission electron microscope. The particle size was analyzed with a particle size analyzer. The surface marker proteins such as cluster of differentiation 9 (CD9), cluster of differentiation 63 (CD63), and cluster of differentiation 81 (CD81) were identified by Western blot, and drug loading capacity was measured by high-performance liquid chromatography (HPLC). An oxidative stress model was induced by alpha, alpha'-azodiisobutyramidine dihydrochloride (AAPH), and Leydig cells were divided into the following groups: A control group, an AAPH group, a quercetin group (Que group), an exosome group (Exo group), and a QUE-loaded Exo group (Que-Exo group). The cell viability was detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) thiazolyl blue assay. The reactive oxygen species (ROS) levels and mitochondrial membrane potential were measured by flow cytometry. The levels of oxidative indicators, including malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and testosterone (T), were detected by enzyme-linked immunosorbent assay (ELISA). The expressions of steroidogenic enzymes such as cytochrome p450 family 11 subfamily a member 1 (CYP11A1), hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 (HSD3B1), and hydroxysteroid 17-beta dehydrogenase 3 (HSD17B3), regulatory factors such as steroidogenic factor 1 (SF-1) and steroidogenic acute regulatory protein (StAR), and miR-145-5p content, were detected by Western blot and real-time polymerse chain reaction (Real-time PCR). ResultsNetwork pharmacology analysis reveals that the main active components of Qiangjing tablet for intervening in male infertility with kidney deficiency and blood stasis syndrome were Que, luteolin, etc., with the core mechanism involving pathways such as steroid hormone biosynthesis. Experimental results show that compared with the control group, the AAPH group exhibits significantly reduced cell viability (P<0.01), decreased mitochondrial membrane potential (P<0.01), significantly elevated levels of ROS, MDA, and miR-145-5p (P<0.01), significantly reduced activities of SOD, GSH-Px, and CAT, as well as reduced testosterone content (P<0.01), and significantly downregulated protein and mRNA expressions of steroidogenic enzymes, SF-1, and StAR (P<0.01). The above indicators were reversed in the Que and Que-Exo groups (P<0.05). Compared with the Que group, the Que-Exo group showed more significant effects in enhancing cell viability, mitochondrial membrane potential, testosterone level, antioxidant enzyme activities, and expressions of key molecules in the steroidogenic pathway (P<0.05). ConclusionThis study demonstrates that Que, an active component of Qiangjing tablet, inhibits oxidative stress reaction, improves mitochondrial function in Leydig cells, upregulates steroidogenic enzyme expression, and restores testosterone production. As a carrier for Que, Exo enhance its stability, delivery efficiency, and biological effect. Additionally, miR-145-5p may be closely associated with testosterone synthesis, though its precise molecular mechanism requires further exploration. By integrating traditional Chinese medicine compounds with modern scientific technology, this research expands the paths for the modernized research of traditional Chinese medicine and opens a novel therapeutic direction with translational potential for clinical intervention of male infertility.
3.Sex-specific imaging-genetic analysis of gray matter volume abnormalities in children with autism spectrum disorder
Xiaotian WANG ; Youyi LI ; Qing YIN ; Xiaolong SHAN ; Huafu CHEN ; Xujun DUAN
Chinese Journal of Psychiatry 2025;58(11):830-842
Objective:This study aims to investigate sex-specific abnormalities?? in gray matter volume (GMV) in Children with autism spectrum disorder (ASD) and their associations with gene expression.Methods:T 1-weighted brain MRI data were collected at the MRI Center of the University of Electronic Science and Technology of China between 2022 and 2023 from 100 children with ASD and 90 typically developing (TD) children. Voxel-based morphometry (VBM) was used to explore GMV differences between ASD boys and TD boys, and between ASD girls and TD girls. Partial least squares regression (PLSR) was performed based on the Allen Human Brain Atlas to identify genes associated with GMV alterations, followed by enrichment analyses. Cell-type-specific expression analyses were used to examine associations across developmental stages and brain structures. Protein-protein interaction (PPI) networks were constructed to identify hub proteins. Results:Compared to TD boys, ASD boys showed increased GMV in the right superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus, temporal pole, parahippocampal gyrus, fusiform gyrus, cuneus, and precuneus, as well as in the bilateral orbital part of the superior frontal gyrus and the gyrus rectus. Decreased GMV was observed in the cerebellar vermis and bilateral cerebellar hemispheres. A total of 635 genes were associated with these GMV alterations, enriched in pathways related to DNA-templated transcription, RNA metabolism and biogenesis, and ion binding. Developmental analysis indicated strong associations with the cerebellum during early, middle-to-late childhood, and adolescence, and with the cerebral cortex in early adulthood. Protein-protein interaction (PPI) network analysis highlighted NOB1, GNL3L, ESF1, TFB2M, and WDR75 as specific hub proteins. Compared to TD girls, ASD girls exhibited increased GMV in the right middle and inferior temporal gyri, temporal pole, and fusiform gyrus, and decreased GMV in the cerebellar vermis and bilateral cerebellar hemispheres. A total of 765 genes were associated, enriched in pathways related to ion channel activity, signal transduction, and regulation of membrane potential. These genes showed strong associations with the amygdala during mid-to-late fetal development, middle-to-late childhood, adolescence, and early adulthood; with the cerebellum during late infancy, early childhood, and early adulthood; with the cerebral cortex during the mid-to-late fetal development, early neonatal period, and adolescence; with the hippocampus during middle-to-late childhood and adolescence; with the striatum during adolescence and early adulthood; and with the thalamus during early-to-mid fetal development, early neonatal period, and early adulthood. PPI network analysis identified ANK3, ANK1, SCN4B, NFKB1, and PXN as specific hub proteins. Conclusion:Both ASD boys and ASD girls exhibit GMV abnormalities compared with TD controls. The specific genes associated with GMV alterations are enriched in distinct biological pathways in boys and girls. Cell-type-specific expression analyses further revealed sex-dependent differences in developmental timing and brain structural correlations, and distinct PPI networks were constructed for each group.
4.Neuroimaging aided diagnosis and transcranial magnetic stimulation interventions for autism spectrum disorder
Xuchu WENG ; Jin JING ; Jianhong LUO ; Xujun DUAN ; Yufeng ZANG ; Xin WANG ; Jiuxing LIANG ; Lixia YUAN ; Xingjie YANG ; Lei LI ; Lizi LIN ; Haiqing XU ; Zhuoming CHEN ; Saijun HUANG ; Qiang CHEN ; Quanying YI ; Maoping LIANG ; Yanjuan CHEN
Chinese Mental Health Journal 2025;39(8):661-670
Autism spectrum disorder(ASD),characterized by unknown etiology and high heterogeneity,ne-cessitates precise diagnostic and intervention strategies.Neuroimaging techniques have shown great promise in un-covering the neural mechanisms of ASD,providing a foundation for aided diagnosis and transcranial magnetic stim-ulation(TMS)interventions.This review highlights that integrating multimodal neuroimaging and developing indi-vidualized indices with developmental specificity can significantly improve the accuracy of ASD diagnosis and clas-sification.Furthermore,TMS interventions guided by functional connectivity derived from functional magnetic reso-nance imaging(fMRI)offer a personalized approach to ASD treatment.
5.The multi-center mid-term clinical outcomes of combined complete preservation of chordal structure mitral valve replacement with total anatomic complete arterial myocardial revascularization for coronary patients with moderate-to-severe or severe ischemic mitral regurgitation
Ke GUO ; Xujun CHEN ; Baoshi ZHENG ; Chao SHI ; Keli HUANG ; Yong CAO ; Chengquan LIAO ; Jingwei CHEN ; Yu LIN ; Chengxin LIU ; Quansheng CAO ; Lin SHEN ; Zhendong WANG
Chinese Journal of Surgery 2025;63(1):58-67
Objective:To evaluate the clinical outcomes of combined complete preservation of chordal structure mitral valve replacement (C-MVR) with total anatomical arterial myocardial revascularization (TACR) in coronary patients with moderate-to-severe or severe ischemic mitral regurgitation (IMR).Methods:This is a retrospective multi-center case series study. Data were retrospectively collected from 127 patients with coronary artery disease with moderate to severe or severe IMR who received TACR with C-MVR from July 2015 to April 2024 in 13 hospitals in China. There were 90 males and 37 females, aged (56.5±10.7) years (range: 33 to 74 years). Perioperative data and follow-up data including left ventricular ejection fraction, left ventricular end-diastolic diameter, and patency rate of arterial grafts of patients were collected. Comparisons were made using paired sample t-test or χ2 test. Results:In this cohort of 127 patients, 67 underwent concurrent tricuspid valve repair. During surgery, 113 grafts of the left internal mammary artery (LIMA), 127 grafts of the left radial artery, 80 grafts of the right radial artery, and 110 grafts of the right internal mammary artery (RIMA) were harvested. The number of the distal anastomosis was 4.2±0.4 (range: 3 to 5). The aortic cross-clamp time and cardiopulmonary bypass time were (97.5±23.4) minutes (range: 90 to 161 minutes) and (145.4±19.2) minutes (range: 101 to 210 minutes), respectively. There was one operative death. Intraoperative placement of an intra-aortic balloon pump was performed in 21 patients to improve the left ventricular ejection. No sternal ischemic occurred. All patients completed follow-up, with a mean follow-up period of (64.3±7.5) months (range: 4 to 110 months). No major cerebrovascular events occurred during the follow-up period, and all patients survived. Left ventricular ejection fraction improved postoperatively (55.0%±5.3% vs. 41.0%±15.3%, t=17.23, P<0.01). The proportion of patients with New York Heart Association functional class ≤2 increased postoperatively (23.6% (30/127) vs. 87.3% (110/126), χ2=103.77, P<0.01). The proportion of patients with Canadian Cardiovascular Society Angina Classification ≤3 decreased postoperatively (4.8% (6/126) vs. 78.7% (100/127), χ2=142.19, P<0.01). The left ventricular end-diastolic diameter decreased postoperatively ((5.70±4.50) cm vs. (6.10±0.23) cm, t=12.15, P<0.01). Coronary multi-detector computed tomography angiography (MDCTA) follow-up was conducted for (60.5±11.7) months (range: 6 to 109 months) postoperatively. MDCTA confirmed the patency rates of the grafts: 96.4% (108/112) for the LIMA grafts, 88.9% (112/126) for the left radial artery grafts, 93.7% (74/79) for the right radial artery grafts, and 90.9% (100/110) for the free RIMA grafts. No significant differences in graft patency rates were observed between the arterial grafts ( χ2=5.24, P=0.155). Conclusion:The results of this multi-centre study demonstrate satisfactory mid-term results of C-MVR with TACR for the treatment of coronary artery disease with moderate to severe or severe IMR.
6.The multi-center mid-term clinical outcomes of combined complete preservation of chordal structure mitral valve replacement with total anatomic complete arterial myocardial revascularization for coronary patients with moderate-to-severe or severe ischemic mitral regurgitation
Ke GUO ; Xujun CHEN ; Baoshi ZHENG ; Chao SHI ; Keli HUANG ; Yong CAO ; Chengquan LIAO ; Jingwei CHEN ; Yu LIN ; Chengxin LIU ; Quansheng CAO ; Lin SHEN ; Zhendong WANG
Chinese Journal of Surgery 2025;63(1):58-67
Objective:To evaluate the clinical outcomes of combined complete preservation of chordal structure mitral valve replacement (C-MVR) with total anatomical arterial myocardial revascularization (TACR) in coronary patients with moderate-to-severe or severe ischemic mitral regurgitation (IMR).Methods:This is a retrospective multi-center case series study. Data were retrospectively collected from 127 patients with coronary artery disease with moderate to severe or severe IMR who received TACR with C-MVR from July 2015 to April 2024 in 13 hospitals in China. There were 90 males and 37 females, aged (56.5±10.7) years (range: 33 to 74 years). Perioperative data and follow-up data including left ventricular ejection fraction, left ventricular end-diastolic diameter, and patency rate of arterial grafts of patients were collected. Comparisons were made using paired sample t-test or χ2 test. Results:In this cohort of 127 patients, 67 underwent concurrent tricuspid valve repair. During surgery, 113 grafts of the left internal mammary artery (LIMA), 127 grafts of the left radial artery, 80 grafts of the right radial artery, and 110 grafts of the right internal mammary artery (RIMA) were harvested. The number of the distal anastomosis was 4.2±0.4 (range: 3 to 5). The aortic cross-clamp time and cardiopulmonary bypass time were (97.5±23.4) minutes (range: 90 to 161 minutes) and (145.4±19.2) minutes (range: 101 to 210 minutes), respectively. There was one operative death. Intraoperative placement of an intra-aortic balloon pump was performed in 21 patients to improve the left ventricular ejection. No sternal ischemic occurred. All patients completed follow-up, with a mean follow-up period of (64.3±7.5) months (range: 4 to 110 months). No major cerebrovascular events occurred during the follow-up period, and all patients survived. Left ventricular ejection fraction improved postoperatively (55.0%±5.3% vs. 41.0%±15.3%, t=17.23, P<0.01). The proportion of patients with New York Heart Association functional class ≤2 increased postoperatively (23.6% (30/127) vs. 87.3% (110/126), χ2=103.77, P<0.01). The proportion of patients with Canadian Cardiovascular Society Angina Classification ≤3 decreased postoperatively (4.8% (6/126) vs. 78.7% (100/127), χ2=142.19, P<0.01). The left ventricular end-diastolic diameter decreased postoperatively ((5.70±4.50) cm vs. (6.10±0.23) cm, t=12.15, P<0.01). Coronary multi-detector computed tomography angiography (MDCTA) follow-up was conducted for (60.5±11.7) months (range: 6 to 109 months) postoperatively. MDCTA confirmed the patency rates of the grafts: 96.4% (108/112) for the LIMA grafts, 88.9% (112/126) for the left radial artery grafts, 93.7% (74/79) for the right radial artery grafts, and 90.9% (100/110) for the free RIMA grafts. No significant differences in graft patency rates were observed between the arterial grafts ( χ2=5.24, P=0.155). Conclusion:The results of this multi-centre study demonstrate satisfactory mid-term results of C-MVR with TACR for the treatment of coronary artery disease with moderate to severe or severe IMR.
7.Epidemiological trends and resistance mechanisms of enterobacterales carrying multiple carbapenemases
Ke WANG ; Qi WANG ; Shuo YANG ; Ruiqi WANG ; Xujun CAI ; Jun HOU ; Hong ZOU ; Yan JIN ; Mei LI ; Hui GUO ; Liang JIN ; Xu YANG ; Lin ZHANG ; Hui WANG
Chinese Journal of Laboratory Medicine 2025;48(9):1158-1164
Objective:To characterize the epidemiology, antimicrobial susceptibility, and molecular mechanisms of carbapenem-resistant Enterobacterales (CRE) carrying multiple carbapenemase genes in China, and to provide evidence for infection control and antibiotic stewardship.Methods:From 2016 to 2023, 115 CRE isolates harboring at least two carbapenemase genes were collected from 41 hospitals in 18 provinces across China. Species identification, antimicrobial susceptibility testing, and whole-genome sequencing were performed. Multilocus sequence typing (MLST) and capsular typing were conducted using Kleborate, plasmid replicon types were identified with PlasmidFinder, and a core genome phylogenetic tree was constructed.Results:The majority of isolates belonged to Klebsiella spp. (80.0%, 92/115), followed by E. cloacae (8.7%, 10/115) and E. coli (6.1%, 7/115). The isolates were mainly from Hebei, Beijing, Shandong, and Hunan (60.9%, 70/115), and sputum was the predominant specimen (43.5%, 50/115). The most common genotype was bla KPC+bla NDM (73.0%, 84/115), primarily in Klebsiella spp. (79.8%, 67/84), followed by bla NDM+bla IMP (15.7%, 18/115). The prevalent plasmid replicon types were IncFII (77.5%, 86/111), IncFIB (68.5%, 76/111), IncR (51.4%, 57/111), and IncX3 (20.7%, 23/111). Notably, 88.6% (31/35) of ST11-KL64 K. pneumoniae strains co-harbored IncFII, IncFIB, and IncR plasmids simultaneously. Between 2016 and 2022, the dominant subtype among Klebsiella spp. isolates was bla KPC-2+bla NDM-1 (56.2%, 36/64). In 2023, the bla KPC-2+bla NDM-13 subtype (29.5%, 19/64) emerged and exhibited clonal transmission (single nucleotide polymorphism 2?74 bp) in Hebei, Beijing, and Jilin. Susceptibility testing showed widespread resistance to β-lactams (90.2%-100%). Aztreonam-avibactam, tigecycline, and colistin retained high activity, with susceptibility rates of 90.16%-98.36%. Conclusions:In China, the majority of clinical Enterobacteriaceae strains that harbor multiple carbapenemases are Klebsiella spp. co-producing KPC and NDM enzymes. Dissemination is driven by both clonal expansion of ST11-KL64 and horizontal transfer of IncFII, IncFIB, and IncR plasmids. The recent emergence and regional clonal spread of the bla KPC-2+bla NDM-13 genotype underscore the urgent need for strengthened surveillance and containment measures.
8.Epidemiological trends and resistance mechanisms of enterobacterales carrying multiple carbapenemases
Ke WANG ; Qi WANG ; Shuo YANG ; Ruiqi WANG ; Xujun CAI ; Jun HOU ; Hong ZOU ; Yan JIN ; Mei LI ; Hui GUO ; Liang JIN ; Xu YANG ; Lin ZHANG ; Hui WANG
Chinese Journal of Laboratory Medicine 2025;48(9):1158-1164
Objective:To characterize the epidemiology, antimicrobial susceptibility, and molecular mechanisms of carbapenem-resistant Enterobacterales (CRE) carrying multiple carbapenemase genes in China, and to provide evidence for infection control and antibiotic stewardship.Methods:From 2016 to 2023, 115 CRE isolates harboring at least two carbapenemase genes were collected from 41 hospitals in 18 provinces across China. Species identification, antimicrobial susceptibility testing, and whole-genome sequencing were performed. Multilocus sequence typing (MLST) and capsular typing were conducted using Kleborate, plasmid replicon types were identified with PlasmidFinder, and a core genome phylogenetic tree was constructed.Results:The majority of isolates belonged to Klebsiella spp. (80.0%, 92/115), followed by E. cloacae (8.7%, 10/115) and E. coli (6.1%, 7/115). The isolates were mainly from Hebei, Beijing, Shandong, and Hunan (60.9%, 70/115), and sputum was the predominant specimen (43.5%, 50/115). The most common genotype was bla KPC+bla NDM (73.0%, 84/115), primarily in Klebsiella spp. (79.8%, 67/84), followed by bla NDM+bla IMP (15.7%, 18/115). The prevalent plasmid replicon types were IncFII (77.5%, 86/111), IncFIB (68.5%, 76/111), IncR (51.4%, 57/111), and IncX3 (20.7%, 23/111). Notably, 88.6% (31/35) of ST11-KL64 K. pneumoniae strains co-harbored IncFII, IncFIB, and IncR plasmids simultaneously. Between 2016 and 2022, the dominant subtype among Klebsiella spp. isolates was bla KPC-2+bla NDM-1 (56.2%, 36/64). In 2023, the bla KPC-2+bla NDM-13 subtype (29.5%, 19/64) emerged and exhibited clonal transmission (single nucleotide polymorphism 2?74 bp) in Hebei, Beijing, and Jilin. Susceptibility testing showed widespread resistance to β-lactams (90.2%-100%). Aztreonam-avibactam, tigecycline, and colistin retained high activity, with susceptibility rates of 90.16%-98.36%. Conclusions:In China, the majority of clinical Enterobacteriaceae strains that harbor multiple carbapenemases are Klebsiella spp. co-producing KPC and NDM enzymes. Dissemination is driven by both clonal expansion of ST11-KL64 and horizontal transfer of IncFII, IncFIB, and IncR plasmids. The recent emergence and regional clonal spread of the bla KPC-2+bla NDM-13 genotype underscore the urgent need for strengthened surveillance and containment measures.
9.Sex-specific imaging-genetic analysis of gray matter volume abnormalities in children with autism spectrum disorder
Xiaotian WANG ; Youyi LI ; Qing YIN ; Xiaolong SHAN ; Huafu CHEN ; Xujun DUAN
Chinese Journal of Psychiatry 2025;58(11):830-842
Objective:This study aims to investigate sex-specific abnormalities?? in gray matter volume (GMV) in Children with autism spectrum disorder (ASD) and their associations with gene expression.Methods:T 1-weighted brain MRI data were collected at the MRI Center of the University of Electronic Science and Technology of China between 2022 and 2023 from 100 children with ASD and 90 typically developing (TD) children. Voxel-based morphometry (VBM) was used to explore GMV differences between ASD boys and TD boys, and between ASD girls and TD girls. Partial least squares regression (PLSR) was performed based on the Allen Human Brain Atlas to identify genes associated with GMV alterations, followed by enrichment analyses. Cell-type-specific expression analyses were used to examine associations across developmental stages and brain structures. Protein-protein interaction (PPI) networks were constructed to identify hub proteins. Results:Compared to TD boys, ASD boys showed increased GMV in the right superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus, temporal pole, parahippocampal gyrus, fusiform gyrus, cuneus, and precuneus, as well as in the bilateral orbital part of the superior frontal gyrus and the gyrus rectus. Decreased GMV was observed in the cerebellar vermis and bilateral cerebellar hemispheres. A total of 635 genes were associated with these GMV alterations, enriched in pathways related to DNA-templated transcription, RNA metabolism and biogenesis, and ion binding. Developmental analysis indicated strong associations with the cerebellum during early, middle-to-late childhood, and adolescence, and with the cerebral cortex in early adulthood. Protein-protein interaction (PPI) network analysis highlighted NOB1, GNL3L, ESF1, TFB2M, and WDR75 as specific hub proteins. Compared to TD girls, ASD girls exhibited increased GMV in the right middle and inferior temporal gyri, temporal pole, and fusiform gyrus, and decreased GMV in the cerebellar vermis and bilateral cerebellar hemispheres. A total of 765 genes were associated, enriched in pathways related to ion channel activity, signal transduction, and regulation of membrane potential. These genes showed strong associations with the amygdala during mid-to-late fetal development, middle-to-late childhood, adolescence, and early adulthood; with the cerebellum during late infancy, early childhood, and early adulthood; with the cerebral cortex during the mid-to-late fetal development, early neonatal period, and adolescence; with the hippocampus during middle-to-late childhood and adolescence; with the striatum during adolescence and early adulthood; and with the thalamus during early-to-mid fetal development, early neonatal period, and early adulthood. PPI network analysis identified ANK3, ANK1, SCN4B, NFKB1, and PXN as specific hub proteins. Conclusion:Both ASD boys and ASD girls exhibit GMV abnormalities compared with TD controls. The specific genes associated with GMV alterations are enriched in distinct biological pathways in boys and girls. Cell-type-specific expression analyses further revealed sex-dependent differences in developmental timing and brain structural correlations, and distinct PPI networks were constructed for each group.
10.Exploration and effectiveness of the integration of biomedical and clinical medical education and teaching reform between China and the UK
Yun HE ; Xujun CHEN ; Jiali WANG ; Jiahe YU ; Yi YANG ; Zhijun LUO
Chinese Journal of Medical Education Research 2025;24(5):583-586
Nanchang University and Queen Mary University of London have integrated their educational and teaching advantageous resources to establish a Sino-foreign cooperative clinical medicine program in China. The program awards the degrees of Bachelor of Science in Biomedical Sciences and Bachelor of Clinical Medicine, aiming to cultivate well-rounded medical talents with both clinical and scientific research capabilities and an international perspective. By introducing biomedical courses and integrating them with basic medical courses, the program emphasizes basic knowledge, practical training, active learning, and the cultivation of scientific research skills and critical thinking ability. The evaluation parameters include academic output, innovation competitions, and the number of students pursuing graduate education. The results showed substantial increases in the number of SCI academic articles published by students in this program, the number of awards in innovation competitions, and the number of students pursuing graduate education. This program is a new attempt in the reform of medical education in China.

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