中南大学学报(医学版)最新文献

{"title":"Research progress in deubiquitinase OTUD3.","authors":"Dan Hou, Dan Yu, Guoshuai Yang, Yujie Hu, Hongxin Li","doi":"10.11817/j.issn.1672-7347.2024.230581","DOIUrl":"10.11817/j.issn.1672-7347.2024.230581","url":null,"abstract":"<p><p>OTU domain-containing protein 3 (OTUD3) is a crucial deubiquitinase that exhibits significant expression differences across various disease models. OTUD3 plays a role in regulating biological functions such as apoptosis, inflammatory responses, cell cycle, proliferation, and invasion in different cell types. By deubiquitinating key substrate proteins, OTUD3 is involved in essential physiological and pathological processes, including innate antiviral immunity, neural development, neurodegenerative diseases, and cancer. OTUD3 exhibits tumor-suppressive effects in breast cancer, esophageal cancer, colon cancer, and papillary thyroid cancer, but acts as an oncogenic in liver and lung cancers. OTUD3 serves as a biomarker in predicting diagnosing, and assessing prognosis for certain malignancies. Despite its potential, the molecular mechanisms of OTUD3 in many diseases are still not well-understood, and exploring OTUD3's regulatory mechanisms is essential for comprehending its roles in immunity and disease. Future research will focus on developing OTUD3-targeted therapies.</p>","PeriodicalId":39801,"journal":{"name":"中南大学学报(医学版)","volume":"49 8","pages":"1341-1352"},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142956373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CPhaMAS: The first pharmacokinetic analysis cloud platform developed by China.","authors":"Yun Kuang, Dongsheng Cao, Dan Jiang, Yonghui Zuo, Feng Lu, Jinghan Yuan, Zhen Fang, Yi Zou, Hong Wang, Chengkun Wu, Qi Pei, Guoping Yang","doi":"10.11817/j.issn.1672-7347.2024.240118","DOIUrl":"10.11817/j.issn.1672-7347.2024.240118","url":null,"abstract":"<p><strong>Objectives: </strong>Software for pharmacological modeling and statistical analysis is essential for drug development and individualized treatment modeling. This study aims to develop a pharmacokinetic analysis cloud platform that leverages cloud-based benefits, offering a user-friendly interface with a smoother learning curve.</p><p><strong>Methods: </strong>The platform was built using Rails as the framework, developed in Julia language, and employs PostgreSQL 14 database, Redis cache, and Sidekiq for asynchronous task management. Four commonly used modules in clinical pharmacology research were developed: Non-compartmental analysis, bioequivalence/bioavailability analysis, compartment model analysis, and population pharmacokinetics modeling. The platform ensured comprehensive data security and traceability through multiple safeguards, including data encryption, access control, transmission encryption, redundant backups, and log management. The platform underwent basic function, performance, reliability, usability, and scalability testing, along with practical case studies.</p><p><strong>Results: </strong>The CPhaMAS cloud platform successfully implemented the 4 module functionalities. The platform provides a list-based navigation for users, featuring checkbox-style interactions. Through cloud computing, it allows direct online data analysis, saving computer storage and minimizing performance requirements. Modeling and visualization do not require programming knowledge. Basic functionality achieved 100% completion, with an average annual uptime of over 99%. Server response time was between 200 to 500 ms, and average CPU usage was maintained below 30%. In a practical case study, cefotaxime sodium/tazobactam sodium injection (6꞉1 ratio) displayd near-linear pharmacokinetics within a dose range of 1.0 to 4.0 g, with no significant effect of tazobactam on the pharmacokinetic parameters of cefotaxime, validating the platform's usability and reliability.</p><p><strong>Conclusions: </strong>CPhaMAS provides an integrated modeling and statistical tool for educators, researchers, and industrial professionals, enabling non-compartmental analysis, bioequivalence/bioavailability analysis, compartmental model building, and population pharmacokinetic modeling and simulation.</p>","PeriodicalId":39801,"journal":{"name":"中南大学学报(医学版)","volume":"49 8","pages":"1290-1300"},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142956429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal stem cell conditioned medium improves hypoxic injury to protect islet graft function.","authors":"Juan Chen, Mengyu Tian, Jianmin Wu, Xingshi Gu, Huaping Liu, Xiaoqian Ma, Wei Wang","doi":"10.11817/j.issn.1672-7347.2024.240349","DOIUrl":"10.11817/j.issn.1672-7347.2024.240349","url":null,"abstract":"<p><strong>Objectives: </strong>Islet transplantation is one of the most promising curative methods for type 1 diabetes mellitus (T1DM), but early hypoxic death of the graft post-transplantation impedes successful treatment. To improve the efficacy of islet transplantation and enhance islet cell resistance to hypoxia, reducing hypoxic injury before revascularization is crucial. Mesenchymal stem cells (MSCs) are known to regulate immune responses and protect against hypoxic damage through paracrine mechanisms. This study aims to verify the protective effects of MSC-conditioned medium (CM) in enhancing islet cells' tolerance to hypoxic conditions and preserving islet graft function.</p><p><strong>Methods: </strong>MIN6 cells were cultured under hypoxic conditions (1% oxygen), and their viability was assessed at different time points using AO/PI staining, observed through fluorescence microscopy. MIN6 cells were treated with varying concentrations of MSC-CM under normal and hypoxic conditions. At different time points, cell viability was measured by Annexin/PI flow cytometry, and insulin secretion capacity was assessed through glucose-stimulated insulin secretion tests. A NCG T1DM mouse model was established, and islet cells from BALB/c mice were co-incubated with MSC-CM for 24 hours. The islet cells were then transplanted under the renal capsule of NCG T1DM mice. Mice body weight and blood glucose levels were monitored, and glucose tolerance tests were conducted to evaluate graft function. Graft survival was further assessed by HE staining and insulin immunohistochemistry.</p><p><strong>Results: </strong>Under hypoxic conditions, MIN6 cell death increased with prolonged hypoxia. Flow cytometry showed that after 48 hours of hypoxia, the survival rate of MIN6 cells was significantly lower than that of the normoxic group [(68.07±7.90)% vs (94.57±2.12)%, <i>P</i><0.01)]. MSC-CM treatment restored the insulin secretion function of MIN6 cells under hypoxia, with the stimulation index (SI) increasing from 1.43±0.06 to 1.77±0.02 (<i>P</i><0.001). Both 10% and 20% MSC-CM effectively mitigated hypoxic damage, whereas 30% MSC-CM had weaker effects. Glucose-stimulated insulin secretion results showed trends consistent with cell survival. Primary mouse islet cells pretreated with 10% MSC-CM and transplanted under the renal capsule of T1DM mice showed a sustained decrease in blood glucose levels 5 days post-surgery. HE staining and insulin immunohistochemistry indicated that the islet cells in the MSC-CM group maintained more intact morphology and higher insulin secretion. Glucose tolerance tests demonstrated better graft function in the MSC-CM group.</p><p><strong>Conclusions: </strong>Hypoxia significantly reduces the survival of MIN6 cells and suppresses their insulin secretion function. However, MSC-CM can significantly improve hypoxia-induced cell death and functional decline, and protect islet graft function in a T1DM mouse transplantation model.</p>","PeriodicalId":39801,"journal":{"name":"中南大学学报(医学版)","volume":"49 8","pages":"1210-1219"},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142956451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of tumor organoids simulating the tumor microenvironment in basic and clinical research of tumor immunotherapy.","authors":"Yizheng Li, Weihua Liao, Lunquan Sun","doi":"10.11817/j.issn.1672-7347.2024.240187","DOIUrl":"10.11817/j.issn.1672-7347.2024.240187","url":null,"abstract":"<p><p>Immunotherapy has led to groundbreaking advances in anti-tumor treatment, yet significant clinical challenges remain such as the low proportion of beneficiaries and the lack of effective platforms for predicting therapeutic response. Organoid technology provides a novel solution to these issues. Organoids are three-dimensional tissue cultures derived from adult stem cells or pluripotent stem cells that closely replicate the structural and biological characteristics of native organs, demonstrating particularly strong potential in modeling the tumor microenvironment (TME). Tumor organoids can simulate TME effectively by retaining endogenous matrix components, including various immune cells, or by adding immune cells, cancer-associated fibroblasts, and other components. This provides a novel platform for predicting immunotherapy outcomes, evaluating adoptive cell therapies, and selecting personalized treatment options for patients. Summarizing strategies for constructing tumor organoids that simulate the microenvironment and understanding their advancements in immunotherapy research and clinical application can provide new insights for the development of tumor immunotherapy.</p>","PeriodicalId":39801,"journal":{"name":"中南大学学报(医学版)","volume":"49 8","pages":"1316-1326"},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142956423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction and biological function of <i>Toxoplasma gondii rop41</i> gene knockout strain.","authors":"Kaijuan Wu, Jing Xie, Xiaohua Liu, Dongqian Yang, Yixiao Wang, Wanchen Zhao, Xiaomin Shang, Liping Jiang","doi":"10.11817/j.issn.1672-7347.2024.240179","DOIUrl":"10.11817/j.issn.1672-7347.2024.240179","url":null,"abstract":"<p><strong>Objectives: </strong>Toxoplasmosis is a zoonotic parasitic disease caused by <i>Toxoplasma gondii</i> (<i>T. gondii</i>), which can lead to complications such as encephalitis and ocular toxoplasmosis. The disease becomes more severe when the host's immune system is compromised. Rhoptry proteins are major virulence factors that enable <i>T. gondii</i> to invade host cells. This study aims to construct a <i>T. gondii</i> rhoptry protein 41 (<i>rop41</i>/ROP41) gene knockout strain and preliminarily investigate the biological function of <i>rop41</i>.</p><p><strong>Methods: </strong>Using CRISPR/Cas9 technology, a specific single-guide RNA (sgRNA) for the target gene was designed and linked to a recombinant plasmid. Homologous fragments were fused with a pyrimethamine resistance gene for selection purposes. The recombinant plasmid and the homologous fragments were electroporated into <i>T. gondii</i>, and PCR identification was performed after drug selection and monoclonal screening. Plaque assays were used to comprehensively assess whether <i>rop41</i> affected the growth and proliferation of <i>T. gondii</i> in host cells. Invasion and proliferation assays were conducted to evaluate the invasion ability of the knockout strain into host cells and its intracellular proliferation capacity. The STRING database was utilized to construct a protein-protein interaction (PPI) network, and functional enrichment analysis was performed to predict the signaling pathways in which ROP41 might be involved.</p><p><strong>Results: </strong>The <i>T. gondii</i><i>rop41</i> gene knockout strain (RH <i>Δku80Δrop41</i>) was successfully constructed and stably inherited. Plaque assays showed that compared with the parental strain, the number of plaques formed by the <i>rop41</i> gene knockout strain did not significantly decrease, but the reduction in plaque size was statistically significant (<i>P</i><0.05). After the <i>rop41</i> gene was knocked out, the invasion ability of <i>T. gondii</i> was reduced, but there was no statistically significant difference in its proliferation ability (<i>P</i>>0.05). The PPI network revealed that ROP41 was associated with other protein kinases and autophagy-related proteins. Enrichment analysis indicated that proteins interacting with ROP41 may be involved in signal transduction, biosynthesis, metabolism, and autophagy-related pathways and could be components of various kinase complexes and phagocytic vesicles.</p><p><strong>Conclusions: </strong>The <i>T. gondii</i> RH <i>Δku80Δrop41</i> strain has been successfully constructed. ROP41 primarily affects the ability of <i>T. gondii</i> to invade host cells and may play a role in signal transduction and autophagy-related pathways between <i>T. gondii</i> and the host.</p>","PeriodicalId":39801,"journal":{"name":"中南大学学报(医学版)","volume":"49 8","pages":"1200-1209"},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142956425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-assembled nanospheres in mucoadhesive microneedle patch for sustained release of triamcinolone in the treatment of oral submucous fibrosis.","authors":"Xian Cheng, Yanqing Yang, Junming Huang, Qiuyun Guo, Wei Zhu, Dingpei Long, Yueying Zhou, Hui Feng, Jie Wang, Yusi Li, Jian Zhou, Yanping Liu, Ousheng Liu","doi":"10.11817/j.issn.1672-7347.2024.240226","DOIUrl":"10.11817/j.issn.1672-7347.2024.240226","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;Drug-loaded mucoadhesive silk fibroin (SF) microneedle patch can overcome the limitations of low bioavailability and significant pain associated with traditional treatment methods, such as topical application or injection of triamcinolone for oral submucous fibrosis (OSF). However, these systems release the drug too quickly, failing to meet the clinical requirements. This study aims to construct a mucoadhesive SF microneedle patch pre-assembled with silk fibroin nanospheres (SFN) and explore its ability to sustain the release of triamcinolone in the treatment of OSF.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;SFN was pre-assembled via precipitation reaction and characterized by scanning electron microscope (SEM) for the morphology. The particle size and ζ-potential were measured by dynamic light scattering (DLS). Triamcinolone was loaded onto SFN using a diffusional post-loading method. The effective loading of triamcinolone was confirmed using Fourier-transform infrared spectroscopy (FTIR). The concentration of unloaded triamcinolone was quantified by high-performance liquid chromatography. Drug encapsulation efficiency and loading capacity of SFN were then calculated to determine the optimal amount of drug loading. The SFN suspension was pre-mixed with SF solution to prepare the microneedle under-layer. The microneedle morphology was observed by SEM. Compression mechanical tests were performed to evaluate the fracture force of microneedles at different nanosphere contents (5%, 10%, and 20%), determining the optimal pre-mixing ratio. Ex-vivo mouse oral mucosa permeation studies were performed to ascertain the insertion depth of the microneedles via histological sections. The adhesive top layer was synthesized using SF and tannic acid, with FTIR confirming its successful synthesis. Its viscoelasticity was characterized by a rheometer, and differential scanning calorimetry analyzed thermal properties. Tensile tests evaluated the interfacial bonding strength between the adhesive layer and microneedle base to ensure no detachment during use. Adhesion to wet oral mucosal tissues was tested and compared to commercial oral patches.Under the optimized conditions, the double-layered mucoadhesive microneedle patch with pre-assembled nanospheres was prepared. Its cell compatibility was evaluated by cell counting kit-8 (CCK-8), live/dead staining, and phalloidin staining after co-culturing with fibroblasts. The drug release experiment was conducted to demonstrate its sustained release efficacy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;SFN (mean diameter 46.25 nm) was successfully prepared. The maximum drug encapsulation efficiency was (63.88±1.09)% (corresponding loading capacity of SFN was (27.41±3.06)% when the weight ratio of triamcinolone/SFN was 0.5. The corporation of SFN did not affect microneedle morphology. The mechanical properties of microneedles decreased with increasing nanosphere amount. Only the fracture force of the group with 5%","PeriodicalId":39801,"journal":{"name":"中南大学学报(医学版)","volume":"49 8","pages":"1245-1260"},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142956364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advantages of disposable portable endoscope in removing thalamic hematoma via the superior parietal lobule.","authors":"Hui Yan, Hao Wu, Jinfu Yang, Jiaode Jiang, Fan Yang, Hui Yang","doi":"10.11817/j.issn.1672-7347.2024.240234","DOIUrl":"10.11817/j.issn.1672-7347.2024.240234","url":null,"abstract":"<p><strong>Objectives: </strong>Thalamic hematoma patients present with diverse clinical conditions, and treatment approaches vary widely. Currently, the use of disposable portable endoscope surgery has been rapidly adopted in many hospitals, but outcomes can vary significantly. Surgical approaches and techniques for thalamic hematoma often reference those used for basal ganglia hemorrhage, but their effectiveness remains uncertain. This study aims to explore the advantages of using disposable portable endoscopes in removing thalamic hematoma via the superior parietal lobule, providing guidelines for clinicians to manage thalamic bleeding effectively.</p><p><strong>Methods: </strong>Clinical data of patients with thalamic hematoma who underwent either disposable portable endoscope or microscope surgery at the Third Xiangya Hospital, Central South University, were retrospectively analyzed. Surgical duration, hematoma clearance rate, length of hospital stay, improvement rate in Glasgow Coma Scale (GCS) score at 24 hours post-operation, and incidence of pulmonary infection were compared between the 2 groups.</p><p><strong>Results: </strong>Compared with the microscope group, the disposable portable endoscope group had shorter operation time, higher hematoma clearance rate, shorter hospital stay, and lower incidence of pulmonary infection (all <i>P</i><0.05). However, there was no significant difference in the improvement rate of GCS score at 24 hours post-operation between the 2 groups (<i>P</i>>0.05).</p><p><strong>Conclusions: </strong>In the surgical removal of thalamic hematoma via the superior parietal lobule, the disposable portable endoscope offers advantages such as shorter surgical duration, better visualization, higher hematoma clearance rate, improved surgical efficiency, shorter hospital stay, and lower incidence of pulmonary infection. Therefore, it can be considered as a preferred surgical treatment option for patients with thalamic hematoma.</p>","PeriodicalId":39801,"journal":{"name":"中南大学学报(医学版)","volume":"49 8","pages":"1261-1270"},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142956421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation of objective and subjective sleep parameters with fatigue and depression in kidney transplant recipients.","authors":"Min Liu, Jianfei Xie, Qian Sun, Yi Zhou, Lifang Liu, Xin Zhou, Jia Liu, Xiaoxia Wu","doi":"10.11817/j.issn.1672-7347.2024.240157","DOIUrl":"10.11817/j.issn.1672-7347.2024.240157","url":null,"abstract":"<p><strong>Objectives: </strong>Sleep quality in kidney transplant recipients is closely associated with symptoms of fatigue and depression. Although subjective assessment tools like the Pittsburgh Sleep Quality Index and the Richards-Campbell Sleep Questionnaire (RCSQ) are widely used to evaluate sleep quality, there is a lack of studies utilizing polysomnography for objective evaluation. This study aims to investigate the correlation between sleep quality, fatigue, and depression in kidney transplant recipients using both subjective and objective methods, providing scientific evidence for improving their quality of life.</p><p><strong>Methods: </strong>The cross-sectional study conveniently sampled 50 kidney transplant recipients from a transplant center in a general hospital between August 2018 and March 2020. Subjective and objective sleep parameters were evaluated using the RCQS and polysomnography, respectively. The Fatigue Severity Scale was used to assess fatigue, and the Hamilton Depression Scale was employed to measure depression levels.</p><p><strong>Results: </strong>A lower proportion of rapid eye movement (REM) sleep was associated with increased fatigue. Additionally, higher wake time percentages and poorer sleep quality were significantly correlated with greater depression severity.</p><p><strong>Conclusions: </strong>This study underscores the critical importance of effectively managing sleep quality in kidney transplant recipients and addressing their fatigue and depression symptoms. These findings lay a foundation for developing targeted nursing and therapeutic strategies.</p>","PeriodicalId":39801,"journal":{"name":"中南大学学报(医学版)","volume":"49 8","pages":"1279-1289"},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142956427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of interaction between individual genomes and preeclampsia on the severity of autism spectrum disorder symptoms.","authors":"Xiaomeng Wang, Dai Wu, Tengfei Luo, Weinü Fan, Jinchen Li","doi":"10.11817/j.issn.1672-7347.2024.240177","DOIUrl":"10.11817/j.issn.1672-7347.2024.240177","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Prior research suggests that genetic susceptibility and environmental exposures, such as maternal preeclampsia (PE) during pregnancy, play key roles in ASD pathogenesis. However, the specific effects of the interaction between genetic and environmental factors on ASD phenotype severity remain unclear. This study aims to investigate how interactions between de novo variants (DNVs) and common variants in individual genomes and PE exposure affect ASD symptom severity by constructing a gene-environment model.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Phenotypic data were obtained from the Simons Simplex Collection (SSC) database for idiopathic ASD patients aged 4-18. Subjects were divided based on maternal PE status: PE&lt;sup&gt;+&lt;/sup&gt; (exposed) and PE&lt;sup&gt;-&lt;/sup&gt; (unexposed) groups. Those without DNVs were divided into DNV&lt;sup&gt;-&lt;/sup&gt;PE&lt;sup&gt;+&lt;/sup&gt; and DNV&lt;sup&gt;-&lt;/sup&gt;PE&lt;sup&gt;-&lt;/sup&gt; groups, and those with DNVs into DNV&lt;sup&gt;+&lt;/sup&gt;PE&lt;sup&gt;+&lt;/sup&gt; and DNV&lt;sup&gt;+&lt;/sup&gt;PE&lt;sup&gt;-&lt;/sup&gt; groups. Based on polygenic risk scores (PRS), subjects below the median were classified into PRS&lt;sup&gt;low&lt;/sup&gt;PE&lt;sup&gt;+&lt;/sup&gt; and PRS&lt;sup&gt;low&lt;/sup&gt;PE&lt;sup&gt;-&lt;/sup&gt; groups, and those at or above the median into PRS&lt;sup&gt;high&lt;/sup&gt;PE&lt;sup&gt;+&lt;/sup&gt; and PRS&lt;sup&gt;high&lt;/sup&gt;PE&lt;sup&gt;-&lt;/sup&gt; groups. Core ASD phenotypic assessed included adaptive and cognitive abilities, social reciprocity, language and communication skills, and repetitive behaviors. Adaptive and cognitive abilities were scored using adaptive behavior composite scores from the Vineland Adaptive Behavior Scales, Second Edition (VABS-II), along with verbal intelligence quotient (VIQ) and nonverbal intelligence quotient (NVIQ) scores from the SSC database. Social reciprocity abilities were measured using the social domain scores from the Autism Diagnostic Interview-Revised (ADI-R SD), social affective domain scores from the Autism Diagnostic Observation Schedule (ADOS SA), and normalized scores from the Social Responsiveness Scale (SRS). Language and communication abilities were assessed through verbal communication domain (ADI-R VC), nonverbal communication domain (ADI-R NVC) scores from ADI-R, and the communication and social domain scores from ADOS (ADOS CS). Repetitive behaviors were measured using the restricted and repetitive behaviors domain scores from ADI-R (ADI-R RRB), the repetitive domain scores from ADOS (ADOS REP), and the overall scores from the Repetitive Behavior Scale-Revised (RBS-R). Linear regression models were constructed to explore the impact of PE exposure and its interaction with individual genomes (including DNVs and common variants) on core ASD phenotypes. Additionally, ASD candidate genes associated with DNVs underwent gene ontology (GO) enrichment analysis via Metascape, and temporal and spatial gene expression patterns were examined using RNA sequencing (RNA-seq) data from the BrainSpan database.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;","PeriodicalId":39801,"journal":{"name":"中南大学学报(医学版)","volume":"49 8","pages":"1187-1199"},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142956447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of <i>WT1</i> gene<b>-</b>guided pre<b>-</b>emptive therapy for prevention of relapse in acute myeloid leukemia after transplantation and its optimal intervention threshold.","authors":"Peng Fang, Yin Gao, Hongya Xin, Linxin Liu, Yi Liu, Yajing Xu, Yan Chen","doi":"10.11817/j.issn.1672-7347.2024.240351","DOIUrl":"10.11817/j.issn.1672-7347.2024.240351","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;Monitoring minimal residual disease (MRD) and timely intervention are effective strategies for preventing relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adult acute myeloid leukemia (AML). The &lt;i&gt;WT1&lt;/i&gt; gene, a pan-leukemia marker, can be used as an indicator for MRD monitoring in AML patients. Currently, there is no unified standard for the intervention timing or treatment threshold based on &lt;i&gt;WT1&lt;/i&gt; gene detection after transplantation. This study aims to evaluate the clinical value of &lt;i&gt;WT1&lt;/i&gt; gene-guided preemptive therapy and further explore its optimal intervention threshold.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Data of adult AML patients with intermediate or high-risk cytogenetics who underwent allo-HSCT between January 2014 and June 2020 at the Department of Hematology, Xiangya Hospital, Central South University, were retrospectively collected. All patients had &lt;i&gt;WT1&lt;/i&gt; gene expression data within three years post-transplantation. We compared the outcomes of &lt;i&gt;WT1&lt;/i&gt;-positive patients who received preemptive therapy with those who did not, and both groups with &lt;i&gt;WT1&lt;/i&gt;-negative patients. The endpoints analyzed included cumulative incidence of relapse (CIR), disease-free survival (DFS) rate, overall survival (OS) rate, and non-relapse mortality (NRM) rate. Data of patients who did not receive any intervention were included to analyze factors that might influence prognosis. Univariate analysis was performed using factors such as age, gender, transplantation type,cytogenetic risk stratification, pre-transplant disease status, pre- and post-transplant &lt;i&gt;WT1&lt;/i&gt; levels, and donor gender; factors with &lt;i&gt;P&lt;/i&gt;&lt;0.10 in univariate analysis were further included in a Cox regression model for multivariate analysis. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off value of &lt;i&gt;WT1&lt;/i&gt; gene expression for predicting relapse.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 165 AML patients were included, of whom 86 had &lt;i&gt;WT1&lt;/i&gt; gene positivity within three years post-transplantation. Among these, 58 received preemptive therapy and 28 did not. Compared with &lt;i&gt;WT1&lt;/i&gt;-negative patients, those &lt;i&gt;WT1&lt;/i&gt;-positive patients who did not receive preemptive therapy had significantly higher 5-year CIR (42.9% vs 10.5%, &lt;i&gt;P&lt;/i&gt;&lt;0.001), lower 5-year DFS (50.0% vs. 80.7%, &lt;i&gt;P&lt;/i&gt;=0.001), and lower 5-year OS (60.7% vs 82.8%, &lt;i&gt;P&lt;/i&gt;=0.018), while the 5-year NRM rates were not significantly different (7.1% vs 8.9%, &lt;i&gt;P&lt;/i&gt;=0.744). For patients who received preemptive therapy, no significant differences in these outcomes were observed (all &lt;i&gt;P&lt;/i&gt;&gt;0.05). Multivariate analysis revealed that post-transplantation &lt;i&gt;WT1&lt;/i&gt; gene positivity was a poor prognostic factor for AML patients (CIR: &lt;i&gt;HR&lt;/i&gt;=6.24, &lt;i&gt;P&lt;/i&gt;=0.000 1; DFS: &lt;i&gt;HR&lt;/i&gt;=2.77, &lt;i&gt;P&lt;/i&gt;=0.009 6). ROC curve analysis indicated that the area under the curve (AUC) for &lt;i&gt;WT1&lt;/i&gt; gene exp","PeriodicalId":39801,"journal":{"name":"中南大学学报(医学版)","volume":"49 7","pages":"1120-1129"},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142956189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}