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    Research progress in the treatment of chronic primary immune thrombocytopenia
    HUANG Zhouxuan, SHAO Jingbo
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (4): 508-516.   DOI: 10.3969/j.issn.1674-8115.2025.04.014
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    Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by isolated thrombocytopenia resulting from increased platelet destruction and impaired platelet production. Although the majority of patients have a relatively good prognosis, 10%‒20% of children and up to 75% of adults may progress to chronic primary immune thrombocytopenia (CITP). These patients exhibit poor response to multiple therapies, leading to a significant decline in quality of life. At present, the treatment strategies for CITP mainly include first-line therapies such as glucocorticoids and gamma globulin, and second-line therapies such as thrombopoietin receptor agonists (TPO-RAs), rituximab, immunosuppressants, and splenectomy. In recent years, with the in-depth research on CITP, some new biological drugs and immunotherapies, such as Fcγ receptor (FcγR) signal transduction inhibitors, neonatal Fc receptor inhibitors, complement inhibitors, immune-cell-targeted therapies, platelet desialylation, umbilical cord mesenchymal stem cell therapy, and chimeric antigen receptor T cell immunotherapy, have shown good therapeutic potential. By targeting specific pathways in the pathogenesis of CITP, these novel therapies aim to achieve individualized precision treatment, thereby providing patients with more effective therapeutic options. This article reviews the pathogenesis, second-line treatment approaches, and therapeutic advances in CITP.

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    Research progress on the role and mechanisms of microglia in inflammatory diseases of central nervous system
    YU Kai, SHUAI Zhewei, HUANG Hongjun, LUO Yan
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (5): 630-638.   DOI: 10.3969/j.issn.1674-8115.2025.05.012
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    Microglia are the resident immune cells in the central nervous system (CNS), and play a dual role in maintaining brain homeostasis and mediating neuroprotection. Under normal conditions, microglia maintain brain homeostasis by monitoring environmental changes. When nerve damage or certain pathological stimuli occur, microglia are rapidly activated and initiate a series of complex immune responses to induce neuroinflammation. This proper activation of microglia can protect the brain by inhibiting or clearing various pathogens, but excessive neuroinflammation can lead to neuronal damage and even death. This imbalance of inflammatory response is one of the core features of pathological development of many CNS inflammatory diseases, such as Alzheimers disease, Parkinsons disease, sepsis-associated encephalopathy, and ischemic strokes. In recent years, with the rapid development of frontier biotechnology such as single-cell sequencing, proteinomics and gene editing, important progress has been made in understanding the molecular mechanism by which microglia participate in CNS inflammatory diseases, especially in the activation of inflammatory corpuscles, epigenetic modifications, and metabolic reprogramming. However, due to the heterogeneity and duality of microglia under different pathological conditions, therapeutic methods targeting microglia have not yet been widely used in clinical practice. In summary, this article takes microglia as the starting point and introduces the molecular mechanisms of their involvement in the occurrence and development of CNS inflammatory diseases and its targeted regulatory treatment strategy, aiming to provide theoretical reference for the subsequent precise regulation of microglia function and the development of more targeted therapeutic drugs.

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    Research progress and considerations for thalassemia gene therapy
    GAO Xinjie, LIU Yan, WANG Dawei
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (5): 540-548.   DOI: 10.3969/j.issn.1674-8115.2025.05.002
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    Traditional treatment modalities for thalassemia include regular blood transfusions and allogenic hematopoietic stem cell transplantation (allo-HSCT). In recent years, autologous transplantation of gene-modified hematopoietic stem cells has emerged as a new curative strategy for transfusion-dependent thalassemia (TDT),which has the potential to replace conventional treatments, and provide lifelong benefits for patients. There are two existing technical approaches for gene therapy of β-thalassemia: gene addition, which involves transducing exogenous β-globin genes into hematopoietic stem cells (HSCs), and gene editing, which utilizes CRISPR-Cas9 or other editing systems to re-activate the expression of γ-globin gene. This article summarizes the marketed products and research progress in clinical trials, aiming to analyze the respective advantages and limitations of these two approaches, and discusses the effectiveness and safety of current gene therapies for β-thalassemia, as well as the future directions for associated technologies, including ex vivo HSC expansion with maintenance of stemness and vector-mediated in vivo gene modification. In terms of clinical translational medicine, this article provides in-depth insights into promising solutions for contemporary challenges confronted in clinical trials, including process development challenges, clinical trial conduct, regulatory approval processes, commercialization and payment systems.

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    Detection efficacy of non-invasive prenatal testing for copy number variations in the recurrent 17p12 region
    ZHANG Lanlan, HAN Xu, LI Niu, WANG Jian, LI Shuyuan
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (3): 310-316.   DOI: 10.3969/j.issn.1674-8115.2025.03.007
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    Objective ·To evaluate the detection efficacy and clinical value of non-invasive prenatal testing (NIPT) for identifying copy number variations (CNVs) in the recurrent 17p12 region, including the peripheral myelin protein 22 (PMP22) gene. Methods ·Pregnant women who underwent NIPT in the International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine between July 2020 and April 2024 were enrolled. Clinical data of individuals indicated as high-risk for microdeletions/duplications in the 17p12 region based on NIPT results were collected. Follow-up was conducted to assess the results of subsequent prenatal diagnosis and chromosomal microarray analysis (CMA) performed on peripheral blood from both the pregnant women and their husband. The positive predictive value (PPV) of NIPT for detecting microdeletions/duplications in the 17p12 region, as well as the underlying causes of false positives, was analyzed. Pregnancy outcomes and related clinical phenotypes of fetuses and pregnant women diagnosed with 17p12 CNVs were followed up. Results ·A total of 61 858 pregnant women underwent NIPT testing. NIPT identified 24 cases (0.04%) as high-risk for CNVs in the 17p12 region, including six cases of high-risk 17p12 microduplication and 18 cases of high-risk 17p12 microdeletion. All 24 pregnant women received genetic counseling, and 21 (87.50%) underwent invasive prenatal diagnosis. Invasive prenatal diagnostic confirmed four fetuses with 17p12 microduplications, nine fetuses with 17p12 microdeletions, and eight fetuses with no abnormalities, yielding a PPV of 61.90% (13/21). CMA analysis of maternal peripheral blood in the eight false-positive cases revealed that all mothers carried 17p12 CNVs. Further analysis of pregnant women with NIPT-indicated maternal CNVs revealed that all of them carried relevant CNVs. Among the 20 women with successful follow-up, the majority had normal deliveries, with only one case choosing to terminate the pregnancy due to a de-novo fetal 17p12 microduplication. Normally delivered fetuses (average age: 1.5 years) were followed up without reporting any significant abnormalities. Of the 16 pregnant women carrying 17p12 CNVs, only two exhibited clinical phenotypes associated with these CNVs, while the others remained asymptomatic. Conclusion ·NIPT demonstrates favorable detection efficacy for CNVs in the 17p12 region. Maternal CNVs are the primary cause of false-positive NIPT results for this region.

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    Study on prediction model and influencing factors of progression-free survival in colorectal cancer
    CHEN Jiaying, CHU Yimin, PENG Haixia
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (3): 324-334.   DOI: 10.3969/j.issn.1674-8115.2025.03.009
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    Objective ·To explore the risk factors affecting progression-free survival (PFS) in colorectal cancer (CRC) patients and establish a corresponding prognostic prediction model. Methods ·A retrospective cohort study was used for analysis, including 533 patients with surgically resected and pathologically confirmed colorectal adenocarcinoma at Tongren Hospital, Shanghai Jiao Tong University School of Medicine, who were randomly divided into a training set (373 cases) and a validation set (160 cases) in a 7:3 ratio. The included clinical data were analyzed using univariate and multivariate Cox proportional hazards models to explore independent factors affecting postoperative PFS in patients with CRC and to establish a clinical prognostic prediction model based on these factors. The discrimination and calibration of the prediction model were evaluated by using concordance index (C-index), area under the receiver operating characteristic (ROC) curve (AUC), calibration curve, and survival curve. The independent effects of age, gender, and American Joint Committee on Cancer (AJCC) cancer stage on prognosis were assessed using multivariate Cox regression analysis. Results ·Multivariate Cox regression analysis revealed that age, smoking history, liver disease, carbohydrate antigen 724 (CA724), and AJCC stage were independent factors influencing PFS. In the training set, the C-index of the PFS model was 0.69, with AUCs of 0.744 and 0.713 at 3 and 5 years, respectively. In the validation set, the C-index of the PFS model was 0.64, with AUCs of 0.706 and 0.683 at 3 and 5 years, respectively. The calibration curves showed that the prediction of PFS for the training and validation sets were close to the standard curve. The survival curves suggested that the progression rate of patients in the low-risk group was significantly lower than that in the high-risk group. Stratified analysis revealed that among patients aged ≥65 years, age, liver disease, and AJCC clinical stage were independent factors affecting postoperative PFS. Among patients aged <65 years, smoking history, CA724, and AJCC clinical stage were independent factors affecting postoperative PFS. For male patients, age, smoking history, CA724, and AJCC clinical stage were independent factors affecting postoperative PFS, while for female patients, liver disease, CA724, and AJCC clinical staging were independent predictors of postoperative PFS. Among patients with AJCC stage Ⅰ‒Ⅱ, age and smoking history were independent factors affecting postoperative PFS, whereas in those with AJCC stage Ⅲ‒⁠Ⅳ, age, liver disease, and CA724 were independent factors affecting postoperative PFS. Conclusion ·The PFS prognostic model established in this study for CRC patients has good discriminative ability and provides clinicians with an effective risk assessment tool.

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    Analysis of dentofacial characteristics in Han Chinese adults with facial harmony
    CHEN Siyue, LI Sitong, GU Kaijun, DU Changxin, ZHU Yanfei, ZHENG Chao, ZHOU Jing, HE Ying, ZHU Min
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (3): 317-323.   DOI: 10.3969/j.issn.1674-8115.2025.03.008
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    Objective ·To establish Downs cephalometric norms for the Han Chinese aged 18‒25 with harmonious faces, and to analyze gender and regional characteristics. Methods ·A stratified sampling approach was used to recruit participants from seven geographic regions across China. Over 30 000 volunteers were screened, and 883 participants with harmonious faces were ultimately included. Basic demographic data were collected, and lateral cephalometric radiographs were taken. Hard tissue measurements were performed with Downs analysis (using anatomical porion). The data were then statistically analyzed to compare gender and regional differences in dentofacial structures. Results ·The gender differences in the four hard tissue measurements, the angle of convexity, A-B plane angle, mandibular plane angle, and occlusal plane angle, were statistically significant (P<0.001). Females showed larger values for the angle of convexity, mandibular plane angle, and occlusal plane angle, but smaller values for the A-B plane angle, compared to males. The gender differences in the interincisal angle, L1 to occlusal plane, L1 to mandibular plane, and U1 to AP plane were not statistically significant. There were regional differences in all 10 measurements of Downs analysis, though some regions shared common features. Specifically, the northeastern, eastern, and southern coastal regions exhibited a smaller facial angle, and larger mandibular plane angle, angle of convexity, occlusal plane angle, and U1 to AP plane. It suggested that, compared to inland regions, individuals from coastal regions tended to have more retrusive chins, steeper mandibular planes, more prominent upper incisors, and more convex hard tissue profiles. Conclusion ·Gender differences exist in the dentofacial hard tissue structures of Han Chinese adults with harmonious faces, primarily in skeletal measurements. Each region has its unique dentofacial characteristics, along with some common features. These differences should be taken into account in clinical diagnosis and treatment for the development of personalized and precise therapeutic strategies.

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    Neferine alleviates intervertebral disc degeneration through KEAP1/NRF2/GPX4 and NF-κB signaling pathways
    WAN Hongjin, HU Yibin, WANG Xin, ZHANG Kai, QIN An, MA Peixiang, MA Hui, ZHAO Jie
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (3): 261-270.   DOI: 10.3969/j.issn.1674-8115.2025.03.002
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    Objective ·To investigate the therapeutic effects of neferine (Nef) on intervertebral disc degeneration (IDD) and the underlying regulatory pathways. Methods ·The effects of Nef on the viability and proliferation of nucleus pulposus cells were assessed using the cell counting kit-8 (CCK-8) assay. Molecular docking software was employed to analyze the potential binding sites of Nef within the Kelch domain of kelch-like ECH-associated protein 1 (KEAP1). Tumor necrosis factor-α (TNF-α) was used to induce ferroptosis and inflammation in nucleus pulposus cells. Western blotting was performed to detect the expression levels of nuclear factor erythroid 2-related factor 2/glutathione peroxidase 4 (NRF2/GPX4) pathway- and nuclear factor-κB (NF-κB) pathway-related proteins under TNF-α stimulation with or without Nef. The effect of Nef on the metabolism of extracellular matrix in nucleus pulposus cells was evaluated using high-density cell culture. A needle puncture-induced IDD rat model was established, and 5 µL of 1.5 μmol/L Nef was injected twice into the intervertebral disc at the Co3/4 level (IDD+Nef group), while an equivalent volume of PBS was injected into the Co2/3 disc (IDD group). After 4 weeks, the intervertebral space height was detected by X-ray, disc degeneration was detected by magnetic resonance imaging, and disc structure was evaluated by histological staining. Results ·The CCK-8 assay revealed that Nef at concentrations of 1.5 μmol/L and below did not inhibit the viability and proliferation of nucleus pulposus cells. Molecular docking results suggested that Nef might activate NRF2 by directly binding to the KEAP1 Kelch domain, thereby reducing the interaction between KEAP1 and NRF2. Western blotting indicated that Nef significantly increased the expression of the key ferroptosis-inhibiting proteins NRF2 and GPX4, while decreasing the expression of the phospho-P65 protein in the NF-κB pathway (all P<0.05). The high-density culture of nucleus pulposus cells demonstrated that Nef mitigated the TNF-α- induced degradation of the extracellular matrix (P<0.05). Animal study results showed that compared to the IDD group, the IDD+Nef group exhibited a greater intervertebral disc space height, a lower Pfirrmann grade (both P<0.05), and a reduced degree of histological degeneration. Conclusion ·Nef may inhibit TNF-α-induced ferroptosis in nucleus pulposus cells by activating the KEAP1/NRF2/GPX4 pathway and reduce TNF-α-induced inflammation and extracellular matrix degradation by suppressing the NF-κB pathway, thereby alleviating IDD in rats.

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    Features of oral peripheral T-cell lymphoma, not otherwise specified
    HUANG Runyu, ZHANG Chunye, ZHANG Ying, ZHAO Zhengyan, YANG Yang, WU Lan
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (5): 653-660.   DOI: 10.3969/j.issn.1674-8115.2025.05.015
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    Objective ·To investigate the clinical manifestations and immunophenotypic features of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), involving the oral cavity. Methods ·The medical histories and pathology records of patients diagnosed with oral PTCL-NOS in the Department of Oral Mucosal Diseases of Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine, between August 2020 and August 2024 were retrospectively analyzed. In addition, 5 databases, including PubMed, Web of Science, Embase, Scopus, and CNKI, were searched, and relevant cases reported internationally from January 2014 to September 2024 were reviewed. Results ·A total of 20 oral PTCL-NOS cases were included, comprising 11 males (55.0%) and 9 females (45.0%). The patients′ ages at initial diagnosis ranged from 25 to 77 years, with a mean age of (52.53±12.94) years. The most common sites were the tongue (25.0%), palate (25.0%), and buccal mucosa (20.0%). Nineteen cases (95.0%) had no B symptoms. The cases were positive for CD3 (19/19), CD4 (11/13), CD8 (7/12), CD2 (5/6), CD7 (5/5), TIA-1 (6/7), GB (9/13), perforin (4/6). EBER expression was negative (8/8). The Ki-67 proliferation index was ≥60% in 85% of cases. Conclusions ·Oral PTCL-NOS is extremely rare and has an aggressive clinical behavior. The oral manifestation presents as deep and large mucosal ulcers with uneven bases, and nodules can be palpable. The pathological features are heterogeneous. Immunophenotype detection is useful for early diagnosis and classification. It is essential for stomatologists to enhance their awareness of this malignancy to avoid delayed diagnosis and treatment.

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    Comparison of DNA and RNA extraction efficiency from blood
    SU Xinglei, LU Ping, PENG Junjie, WANG Zimin, SONG Ping, HAN Da
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (4): 476-486.   DOI: 10.3969/j.issn.1674-8115.2025.04.010
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    Objective ·To comprehensively evaluate the efficiency of different kits and methods for DNA and RNA extraction from blood samples. Methods ·A total of 145 blood samples were collected, including those from patients with Alzheimer's disease (20 cases), fibrosis (5 cases), colorectal cancer (108 cases), and healthy individuals (12 cases). A column-based kit (Kit A) and a nucleic acid extraction instrument were used to extract genomic DNA (gDNA) from leukocytes in the blood. Cell-free DNA (cfDNA) and cell-free RNA (cfRNA) in plasma were extracted using five different kits (Kit B‒F), which employed either column-based (Kit B, E) or magnetic bead-based methods (Kit C, D, F). The extraction process of Kit B was optimized by increasing the plasma sample volume and extending the elution incubation time. Furthermore, this protocol was applied to extracting cfDNA from plasma samples of 100 colorectal cancer patients. Quantitative real-time PCR (qPCR) was used to quantify the extracted DNA and RNA, and the molecular yields were compared to evaluate the extraction efficiency. A comprehensive assessment was conducted, considering factors such as cost and operation time. Results ·In gDNA extraction, although the the operation time was shortened by using the nucleic acid extraction instrument, the median number of DNA molecules extracted using Kit A (column-based method) was 25.36-fold higher than that obtained with the instrument (P<0.05). For cfDNA extraction, while the overall efficiency of the three kits (Kit B‒D) was similar, Kit B (column-based method) showed superior performance in low-concentration samples, with average DNA yields 4.24-fold and 1.18-fold higher than those of Kit D and Kit C (both magnetic bead-based). Optimization of Kit B's extraction protocol further improved cfDNA yield. When comparing three samples, the cfDNA yields from larger plasma input volumes was 3.98-fold, 2.38-fold, and 3.82-fold higher than those from smaller input volumes, respectively. The results of cfDNA extraction from 100 colorectal cancer patients indicated that this extraction protocol reliably extracted sufficient amounts of cfDNA from clinical samples. For cfRNA extraction, Kit E (column-based method) was widely recommended due to its high efficiency, convenience, and cost-effectiveness. The median RNA content extracted using Kit E was 5.01-fold higher than that of Kit F (magnetic bead-based method). Lastly, a comparison of the copy numbers of cfDNA and cfRNA in plasma revealed that the average copy number of cfRNA per milliliter of plasma was 27.65-fold higher than that of cfDNA. Conclusion ·Kit A, Kit B, and Kit E show outstanding performance in leukocyte gDNA extraction, plasma cfDNA extraction, and plasma cfRNA extraction, respectively. However, although Kit E has advantages in extraction efficiency and cost, its safety requires further evaluation.

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    Analysis of transcriptome and chromatin accessibility changes during the differentiation of human embryonic stem cells into neural progenitor cells
    LI Linying, CAI Xiaodong, TONG Ran, YANG Chen, WANG Zhiming, HE Xiaoyu, MA Ziyue, ZHANG Feng, LI Lingjie, ZHOU Junmei
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (4): 387-403.   DOI: 10.3969/j.issn.1674-8115.2025.04.001
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    Objective ·To investigate the changes in transcriptome and chromatin accessibility during the differentiation of human embryonic stem cells (hESCs) into neural progenitor cells (NPCs) using in vitro differentiation models and high-throughput multi-omics sequencing technologies. Methods ·hESCs were first induced to differentiate into NPCs in vitro using the embryoid body formation method, and cells at both stages were collected. The cell phenotypes were identified by reverse transcription-quantitative real-time PCR (RT-qPCR) and immunofluorescence (IF) staining. Transcriptome sequencing (RNA-seq) was conducted to detect and analyze the differentially expressed genes (DEGs) between hESCs and NPCs. The assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) was employed to assess chromatin accessibility changes between hESCs and NPCs. Motif enrichment analysis was performed on differentially accessible chromatin regions to discover potential regulatory transcription factors. Finally, an integrated analysis of RNA-seq and ATAC-seq data and the protein-protein interaction (PPI) network were performed to identify key genes and regulatory pathways involved in the early stages of neural differentiation in vitro. Results ·Both RT-qPCR and IF results indicated that the expression levels of pluripotency markers (NANOG and POU5F1) were high at the hESC stage but significantly decreased at the NPC stage, while early neural differentiation markers (PAX6, SOX1, and NES) were minimally expressed at the hESC stage but markedly upregulated at the NPC stage. RNA-seq analysis revealed that compared to the hESC stage, there were 5 597 genes upregulated and 3 654 genes downregulated at the NPC stage. Gene function enrichment analysis showed that the upregulated genes at the NPC stage were enriched in the functions related to neural development. ATAC-seq analysis demonstrated a total of 27 491 genomic regions had significant changes in chromatin accessibility during the differentiation from hESC to NPC, with 12 381 regions showing increased accessibility and 15 110 regions showing decreased accessibility. Motif enrichment analysis revealed that transcription factor genes such as DLX1 and LHX2 might play an important role in the differentiation process from hESCs into NPCs. Integrated analysis of RNA-seq and ATAC-seq data revealed that overlapping genes with high expression at the NPC stage were mainly enriched in axon guidance, forebrain development, and neuron migration. After neural differentiation, the expression levels of CTNND2 and LHX2 genes increased, and the chromatin accessibility of related genomic regions also increased. PPI network analysis indentified candidate downstream genes including PRKACA, CDH2, and ERBB4. Conclusion ·The in vitro differentiation model of hESCs combined with high-throughput multi-omics sequencing technologies can be used to depict the changes in transcriptome and chromatin accessibility during the differentiation of hESCs into NPCs. In this process, the expression levels of genes related to axon guidance, forebrain development, and neuronal migration pathways increase and related chromatin accessibility is enhanced.

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    Clinical management of heart failure with improved ejection fraction: treatment and maintenance
    XU Tianyun, SHEN Yiming, JIANG Meng
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (4): 493-499.   DOI: 10.3969/j.issn.1674-8115.2025.04.012
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    In patients with heart failure with reduced ejection fraction (HFrEF), some individuals demonstrate significant improvement in left ventricular ejection fraction (LVEF) during subsequent evaluations after treatment. The 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America (AHA/ACC/HFSA) heart failure management guidelines introduced the term "heart failure with improved ejection fraction (HFimpEF)" to describe patients with prior LVEF≤40% that subsequently increased above 40% during follow-up. Studies indicate that HFimpEF patients exhibit lower all-cause mortalities and heart failure rehospitalization rates, with a significantly better prognosis compared to HFrEF patients, establishing HFimpEF as a staged therapeutic target for HFrEF. Current discussion on HFimpEF primarily focuses on two aspects: characteristics of the target population and effective methods for LVEF improvement, and maintenance strategies for cardiac function preservation in HFimpEF patients; particularly the latter lacks clear clinical-guideline recommendations. Therefore, reviewing existing research to systematically summarize therapeutic strategies that promote the HFrEF-to-HFimpEF transition and effective maintenance approaches for HFimpEF becomes crucial. This article comprehensively reviews the LVEF-improving effects of current pharmacological, device-based, and surgical interventions, along with monitoring and management strategies for HFimpEF patients. In HFrEF patients, clinical evidence suggests that β-blockers and cardiac resynchronization therapy can significantly improve LVEF beyond 40%. Regarding HFimpEF management, sodium-glucose cotransporter-2 inhibitors (SGLT2i) and renin-angiotensin system inhibitors (RASi) demonstrate efficacy in maintaining LVEF and cardiac function. Additionally, this review identifies current research limitations in HFimpEF and proposes potential future research directions.

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    A randomized controlled study on the effect of intermittent theta burst stimulation on craving, mood, and cognitive function in alcohol-dependent patients during the withdrawal period
    WANG Haihong, YUAN Chenxin, GAN Hong, JIANG Haifeng, ZHAO Yan, DU Jiang, ZHANG Yi
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (3): 349-356.   DOI: 10.3969/j.issn.1674-8115.2025.03.012
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    Objective ·To explore the effect of intermittent theta burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex (DLPFC) on reducing craving in alcohol-dependent patients during the withdrawal period, as well as its impact on patients' emotions and cognitive functions. Methods ·A total of 41 inpatients with alcohol dependence in the withdrawal period were recruited from the Addiction Department of Mental Health Center, Shanghai Jiao Tong University School of Medicine, and randomly assigned to the experimental group (20 patients) and the control group (21 patients). Both groups received routine inpatient treatment for alcohol-dependence. The experimental group received real iTBS stimulation targeting the left DLPFC on the basis of routine inpatient treatment, while the control group received sham stimulation with the same parameters. The intervention course lasted for 2 weeks, with a total of 10 sessions. The Visual Analogue Scale (VAS), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) were used to measure the craving, anxiety, and depression of the patients before and after the intervention. The behavioral tasks of the detection task (DET), identification task (IDN), two back task (TWOB), the Groton maze learning task (GML), and international shopping list task (ISL) in the CogState software package were used to assess the cognitive processing speed, attention/vigilance, working memory, spatial problem-solving/error monitoring ability, and verbal learning and memory of the patients before and after the intervention. Results ·Repeated measures ANOVA showed that the time effect [F=126.713, P<0.001, partial η² (ηp2)=0.765] and interaction effect (F=7.080, P=0.011, ηp2=0.154) of the VAS scores in the two groups of patients were statistically significant. The time effect (F=9.114, P=0.004, ηp2=0.189), group effect (F=5.557, P=0.024, ηp2=0.125), and interaction effect (F=4.977, P=0.032, ηp2=0.113) of the TWOB score were all statistically significant. Only the time effects of BDI (F=45.273, P<0.001, ηp2=0.578), BAI (F=31.432, P<0.001, ηp2=0.473), GML (F=8.993, P=0.005, ηp2=0.209), and ISL (F=26.657, P<0.001, ηp2=0.439) scores were statistically significant. There were no statistically significant effects of time, group, or interaction on the DET and IDN scores. Simple effect analysis showed that the VAS score of the real stimulation group was lower than that of the sham stimulation group after the intervention (F=8.805, P=0.005, ηp2=0.184), and the TWOB score of the real stimulation group was higher than that of the sham stimulation group (F=11.293, P=0.002, ηp2=0.225). Conclusion ·Combining iTBS with routine inpatient treatment can enhance the efficacy of reducing alcohol craving in alcohol-dependent patients during the withdrawal period, and improve their working memory.

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    Integrated single-cell and transcriptome sequencing to construct a prognostic model of M2 macrophage-related genes in prostate cancer
    TANG Kairan, FENG Chengling, HAN Bangmin
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (5): 549-561.   DOI: 10.3969/j.issn.1674-8115.2025.05.003
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    Objective To explore the prognostic value of M2 macrophage-related genes in prostate cancer (PCa), aiming to predict tumor prognosis more accurately and enable personalized treatment. Methods ·RNA sequencing (RNA-seq) data of PCa were downloaded from The Cancer Genome Atlas (TCGA) database, and single-cell RNA sequencing (scRNA-seq) data were obtained from the Gene Expression Omnibus (GEO) database. The immune infiltration of TCGA samples was assessed using the CIBERSORTx algorithm. Differential genes in scRNA-seq data were identified using the FindMarkers function, and immune cell subtypes were characterized. M2 macrophage-related pathways and interactions with surrounding cells were explored through Gene Set Enrichment Analysis (GSEA) and the CellChat algorithm. M2 macrophage signature genes were selected to construct a prognostic model for PCa using univariate Cox and LASSO analyses. Based on the risk model, clinical characteristics, immune suppression, drug resistance, and drug sensitivity analyses were conducted. Results ·In TCGA samples, patients with high M2 macrophage infiltration exhibited significantly lower progression-free survival (PFS). scRNA-seq analysis identified multiple subpopulations of tumor microenvironment (TME) cells. M2 macrophages interacted with various immune cells in TME, contributing to an immunosuppressive microenvironment and playing a key role in tumor promotion. Based on these findings, a PCa risk model was developed, incorporating TREM2, OTOA, SIGLEC1, and PLXDC1, which showed robust predictive performance in both training and validation cohorts. Patients with higher risk scores demonstrated a more immunosuppressive TME, decreased androgen receptor (AR) signaling activity, and worse clinical characteristics, leading to poorer outcomes. Drug prediction and sensitivity analyses identified six potential therapeutic agents that may offer improved efficacy for patients with higher risk scores. Conclusion ·A prognostic model based on M2 macrophage-related genes in the TME has been constructed, providing a theoretical foundation for precision treatment in PCa.

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    Therapeutic effect of combined vitamin D and DHA supplementation on preschool children with attention deficit hyperactivity disorder
    ZHANG Yue, ZHANG Lishan, DING Xiaoyuan, SHEN Zhimin, BIAN Zouji, YU Xiaodan
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (5): 570-577.   DOI: 10.3969/j.issn.1674-8115.2025.05.005
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    Objective ·To investigate the therapeutic effect of combined vitamin D and docosahexaenoic acid (DHA) supplementation on preschool children with attention deficit hyperactivity disorder (ADHD). Methods ·From April 2021 to May 2021, a total of 1 412 children aged 4 to 6 years from eight kindergartens in Pudong New Area of Shanghai, including Tangqiao Street, Chuansha Town, and Heqing Town, were randomly selected by stratified cluster random sampling method. Attention and hyperactivity symptom assessment was performed using the Conner′s Scale, Diagnosis and Statistical Manual of Mental Disorders(fifth edition, DSM-Ⅴ), and Swanson, Nolan, and Pelham (version Ⅳ, SNAP-Ⅳ) Scale, and other neurodevelopmental disorders were excluded using the Wechsler Intelligence Scale. A total of 82 preschool children with ADHD were enrolled, and after fully informing them of the intervention measures, they were divided into an intervention group (n=64) and a control group (n=18) based on their parents′ choice. The control group received routine health education. In addition to routine health education, the intervention group received daily supplementation of Vitamin D (800 IU) and DHA (400 mg). Venous blood samples were collected from both groups at baseline, 3 months, and 12 months for the measurement of serum 25 hydroxy vitamin D [25 (OH) D] and DHA levels. ADHD symptoms were evaluated using Conner′s Scale, SNAP-Ⅳ Scale, and DSM-Ⅴ. Results ·After 3 and 12 months of intervention in the intervention group, serum 25 (OH) D levels and DHA levels were significantly higher (P<0.05), the ADHD symptom scores, including impulsivity-hyperactivity and hyperactivity index scores in Conner′s Scale, the attention and hyperactivity/impulsivity scores in SNAP-Ⅳ Scale, and the attention and hyperactivity/impulsivity scores in DSM-Ⅴ, were significantly reduced compared with the scores before the intervention (P<0.05). There was no significant difference in serum 25 (OH) D and DHA levels, or ADHD symptom scores, at the 3- and 12-month follow-ups compared to baseline. After 3 months of nutritional intervention in the intervention group, the hyperactivity/impulsivity scores in SNAP-Ⅳ Scale and DSM-Ⅴ were significantly improved compared to the control group (P<0.05). After 12 months of intervention, conduct problems, impulsive-hyperactivity and hyperactivity index scores in Conner′s Scale, and hyperactivity/ impulsivity scores in SNAP-Ⅳ Scale and DSM-Ⅴ showed significant improvement compared to the control group (P<0.05). Conclusion ·Combined supplementation with vitamin D and DHA significantly improves serum 25 (OH) D and DHA levels and alleviates ADHD symptoms in preschool children.

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    Effects and mechanisms of liraglutide in ameliorating liver fibrosis in NAFLD mice
    WANG Renjie, ZHU Chaoyu, FANG Yunyun, XIAO Yuanyuan, WANG Qianqian, SONG Wenjing, WEI Li
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (4): 415-425.   DOI: 10.3969/j.issn.1674-8115.2025.04.003
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    Objective ·To investigate the effects of liraglutide on liver fibrosis in mice with non-alcoholic fatty liver disease (NAFLD) and the underlying mechanisms. Methods ·Twenty 8-week-old C57BL/6J mice were randomly divided into a normal chow diet group (Chow group) and a methionine-choline-deficient (MCD) diet group (MCD group), with 10 mice per group. The MCD diet was used to induce NAFLD. Each group was further divided into two subgroups, resulting in four subgroups: Chow+saline, Chow+liraglutide, MCD+saline, and MCD+liraglutide group. After daily intraperitoneal injection of liraglutide (400 μg/kg) or an equivalent volume of saline for 4 weeks, an intraperitoneal glucose tolerance test (IPGTT) was performed. Serum levels of aspartate transaminase (AST), alanine aminotransferase (ALT), total cholesterol (TC), triglyceride (TAG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured. Liver tissues were collected post-euthanasia to assess TAG content. Histopathological changes, lipid deposition, and fibrosis were evaluated via hematoxylin-eosin (HE) staining, Oil Red O staining, and Masson staining. Real-time quantitative PCR (qPCR) and Western blotting were used to analyze the expression of α-smooth muscle actin (α-SMA), fibronectin (FN), collagen type Ⅰ α (COL1A), matrix metalloproteinase 9 (MMP9), tissue inhibitor of metalloproteinase 1 (TIMP1), transforming growth factor β (TGF-β), SMAD3, and phosphorylated SMAD3 (pSMAD3). Results ·The IPGTT revealed that liraglutide intervention reduced blood glucose levels at 15, 30, and 60 min, with a decreased area under the curve (AUC) (both P<0.05). Biochemical analysis showed that liraglutide lowered AST and ALT levels (both P<0.001), increased TC and HDL-C levels (both P<0.05), but had no significant effect on TAG or LDL-C in MCD mice. HE staining and Oil Red O staining revealed reduced lipid droplets, ballooning degeneration, and inflammatory infiltration in hepatocytes after liraglutide treatment. Masson staining indicated decreased collagen fiber deposition in the liver. qPCR and Western blotting analysis demonstrated upregulated expression of α-SMA, FN, COL1A, TIMP1, TGF-β, and pSMAD3/SMAD3, alongside downregulated MMP9 in MCD mice. Liraglutide reversed these changes, lowering α-SMA, FN, COL1A, TIMP1, TGF-β, and pSMAD3/SMAD3 expression while increasing MMP9 expression. Conclusion ·Liraglutide ameliorates liver injury, lipid deposition, and fibrosis in NAFLD mice, through modulation of the TGF-β/SMAD3 pathway and regulating fibrosis-associated protein expression.

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    Phosphatidylethanolamine promotes macrophage senescence and liver injury by activating endoplasmic reticulum stress
    HAN Longchuan, LI Yue, ZOU Zhihui, LUO Jing, LI Ruoyi, ZHANG Yingting, TANG Xinxin, TIAN Lihong, LU Yuheng, HUANG Ying, HE Ming, FU Yinkun
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (6): 693-704.   DOI: 10.3969/j.issn.1674-8115.2025.06.004
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    Objective ·To investigate the effects and molecular mechanisms of phosphatidylethanolamine (PE) on macrophage senescence and its senescence-associated secretory phenotype (SASP), as well as its pathophysiological role in liver injury. Methods ·A macrophage senescence model was established using doxorubicin (DOX), followed by PE treatment. A mouse liver injury model was generated via intraperitoneal co-administration of PE and lipopolysaccharide (LPS) to investigate the effects of PE on liver injury. Senescence markers and SASP factors, including senescence-associated β-galactosidase (SA-β-gal), cell cycle inhibitor p21, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), were evaluated using SA-β-gal staining, quantitative real-time PCR, and Western blotting. RNA sequencing (RNA-seq) was performed, followed by Gene Ontology (GO) cellular component enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, Gene Set Variation Analysis (GSVA), and Gene Set Enrichment Analysis (GSEA), to explore the molecular mechanisms and signaling pathways by which PE promotes macrophage senescence. The expression of endoplasmic reticulum (ER) stress-related proteins, including inositol-requiring enzyme 1 α (IRE1α), spliced X-box binding protein 1 (XBP1s), activating transcription factor 6 (ATF6), ATF4, and C/EBP homologous protein (CHOP), was analyzed through in vivo and in vitro experiments. Results ·PE significantly promoted the expression of senescence markers SA-β-gal, p21, p16 and SASP factors. RNA-seq analysis revealed that ER stress was involved in PE-induced promotion of SASP. Further experiments demonstrated that PE activated the ER stress signaling pathway, promoting macrophage senescence and the expression of SASP factors. In vivo experiments further confirmed that PE exacerbated LPS-induced liver injury in mice through ER stress. Conclusion ·PE promotes macrophage senescence and the expression of SASP factors by activating ER stress signaling pathway, thereby aggravating LPS-induced liver injury.

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    Advances in nanomaterials for promoting bone tissue regeneration by reducing reactive oxygen species levels
    LU Jiayi, LIU Jinzhe, GUO Shangchun, TAO Shicong
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (4): 487-492.   DOI: 10.3969/j.issn.1674-8115.2025.04.011
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    Reactive oxygen species (ROS) are common products of bone tissue injury. If ROS cannot be removed in time, oxidative stress will be induced in the cells, which will have a negative effect on the regeneration of bone tissue. In recent years, with the deepening of research, nanomaterials capable of reducing ROS levels have shown increasing potential in promoting bone tissue regeneration. Currently, nanomaterials applied to reduce ROS levels mainly include those with surface modifications and microstructural designs, dopant-modified inorganic materials, functionalized polymeric materials and hydrogels, and nano-enzymatic materials. However, the clinical application of these nanomaterials is still limited due to their potential cytotoxicity and the lack of sufficient clinical trials. This literature review summarises the research on the use of nanomaterials to reduce ROS levels to promote bone regeneration and provides ideas for the future design and development of novel nanomaterials in this field.

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    Impact of transcranial magnetic stimulation therapy on the volumes of amygdala and hippocampal subfields in patients with major depressive disorder
    WANG Sirui, KONG Gai, LI Hui, QIAN Zhenying, CUI Huiru, TANG Yingying
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (4): 434-442.   DOI: 10.3969/j.issn.1674-8115.2025.04.005
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    Objective ·To investigate the longitudinal changes in amygdala and hippocampal subfield volumes before and after transcranial magnetic stimulation (TMS) treatment in patients with major depressive disorder (MDD) and explore their correlation with the antidepressant and anxiolytic efficacy of TMS. Methods ·A total of 58 patients diagnosed with MDD at Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, were included in this study between January 2018 and August 2023. Clinical depressive and anxiety symptoms were assessed by using the Hamilton Depression Scale (HAMD), Montgomery-Asberg Depression Rating Scale (MADRS), and Hamilton Anxiety Scale (HAMA) at baseline and post-TMS treatment. Patients underwent a baseline magnetic resonance imaging (MRI) scan followed by TMS treatment targeting the left dorsolateral prefrontal cortex (DLPFC) at a frequency of 10 Hz, totaling 20 sessions. A follow-up MRI scan was conducted on the same day the TMS treatment concluded. Amygdala and hippocampal subfield volumes were segmented and calculated by using FreeSurfer v6.0.0 software. Longitudinal changes in the subfield volumes were analyzed with two-way analysis of variance. Controlling for age, sex, and intracranial volume, partial correlation analysis was conducted between subfield volumes and baseline clinical scores. The association between the rate of volume change in brain regions with significant volume changes and symptom improvement (reduction in HAMD, MADRS, and HAMA scores) was evaluated. Results ·Following TMS treatment, a significant increase in the volume of the right amygdala central nucleus was observed (t=-2.441, P=0.018). While the volumes of bilateral hippocampal fimbria decreased, the volumes of most hippocampal subfield and the total hippocampus increased (P<0.05). No significant correlations were found between baseline amygdala or hippocampal subfield volumes and clinical depressive and anxiety symptoms. However, only in patients who responded effectively to TMS treatment, a positive correlation was found between the volume change rate of the left hippocampal tail and reductions in anxiety symptoms (HAMA: r=0.334, P=0.044). Conclusion ·High-frequency TMS targeting the left DLPFC may induce volume increases in the right amygdala central nucleus and specific hippocampal subfields. Additionally, the volume change rate of the left hippocampal tail is associated with anti-anxiety effects in TMS responders, suggesting that high-frequency TMS targeting the left DLPFC may induce neuroplastic changes in the central nucleus of the right amygdala and key subfields of the hippocampus.

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    A nomogram based on ultrasound scoring parameters and clinical indicators for differentiating primary Sjgren′s syndrome from IgG4-related sialadenitis
    LIU Chuxuan, ZUO Jiaxin, XIONG Ping
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (3): 373-380.   DOI: 10.3969/j.issn.1674-8115.2025.03.015
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    Objective ·To construct and validate a nomogram for distinguishing primary Sjὅgren′s syndrome (PSS) from immunoglobulin G4-related sialadenitis (IgG4-RS) based on ultrasound scoring parameters and clinical indicators. Methods ·A total of 141 patients with PSS and 31 patients with IgG4-RS were retrospectively recruited from Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine from January 2018 to December 2023. The ultrasound scoring parameters, including parotid gland ultrasound (PGUS) score, submandibular gland ultrasound (SMGUS) score, and salivary gland ultrasound (SGUS) score, along with clinical indicators such as gender, age, anti-SSB/La antibody, anti-SSA/Ro60 antibody, anti-SSA/Ro52 antibody, IgG, and rheumatoid factor (RF), were collected. The optimal US scoring parameters and clinical indicators were screened by least absolute shrinkage and selection operator (LASSO) regression, and a nomogram model was constructed to distinguish PSS from IgG4-RS. The internal validation of the model was carried out through bootstrap method. Receiver operator characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were used to estimate the discrimination, calibration, and clinical utility of the nomogram model, respectively. Results ·LASSO regression identified six major variables: gender, age, anti-SSA/Ro60 antibody, anti-SSA/Ro52 antibody, PGUS score, and SMGUS score. These variables were used to construct the nomogram. ROC curve of the nomogram showed that the area under the curve (AUC) was 0.976, indicating the nomogram had strong discrimination ability. The bootstrap method was used for internal validation with 1 000 resampling iterations, and the average absolute error was 0.018. Calibration curve demonstrated good agreement between predicted and observed values. DCA indicated that the nomogram had certain clinical utility. Conclusion ·The nomogram based on ultrasound scoring parameters and clinical indicators demonstrates excellent discrimination and calibration in differentiating PSS from IgG4-RS. It has the potential to assist in clinical diagnosis and decision-making.

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    Single narrow-diameter implant-supported dual-unit cantilever restorations for consecutive missing teeth in the anterior mandible: a 3D finite element analysis
    BAO Renqiang, LÜ Chengqi, YU Lüfeng, LU Jiayu, ZOU Derong
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (3): 301-309.   DOI: 10.3969/j.issn.1674-8115.2025.03.006
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    Objective ·To evaluate the applicability of dual-unit cantilever restorations supported by a single narrow-diameter implant for consecutive missing teeth in the anterior mandibular region. Methods ·A simplified mandibular anterior jaw model and a dual-unit cantilever model supported by a single narrow-diameter implant were constructed. The dimensions of the mandibular anterior bone block were set to 20 mm (length), 5 mm (width), and 15 mm (height). The narrow-diameter implant used was the Axiom 2.8 two-stage implant, 2.8 mm×10 mm, paired with a 2.5 mm straight abutment. Based on calculations, the edentulous gap ranged from 5.8 mm to 11.6 mm, leading to the creation of seven crown models with mesiodistal widths of 5.8, 6.8, 7.8, 8.8, 9.8, 10.8, and 11.8 mm. The implant, crowns, and jaw model were assembled using Siemens Nx 12.0 software, and the data were imported into Ansys Workbench 18.0 for finite element analysis. A vertical load of 100 N and a 30° oblique load were applied to simulate occlusal forces. The Von-Mises stress on the implants, as well as the maximum compressive and tensile stresses in the cortical bone and the maximum tensile stress in the cancellous bone, was analyzed to investigate stress distribution under varying cantilever lengths. Results ·The implant neck region exhibited the highest stress concentration. As the cantilever length increased, the peak Von-Mises stress on the implants, the maximum tensile stress in the cortical and cancellous bones, and the maximum compressive stress in the cortical bones all increased progressively. However, all stress values remained within physiological limits. The peak Von-Mises stress ranged from 141.52 MPa to 707.17 MPa, below the implant′s ultimate tensile strength of 930 MPa. The maximum tensile stress in the cortical bones (with a peak of 60.82 MPa in the 11.8 mm group) was below the cortical bone′s tensile strength limit of 100‒130 MPa. The maximum compressive stress in the cortical bone (with an absolute maximum value of 129.39 MPa in the 11.8 mm group) was below the cortical bone′s compressive strength limit of 170 to 190 MPa (absolute values). The maximum tensile stress in the cancellous bone ranged from 0.84 MPa to 4.70 MPa, which was below or close to its ultimate tensile strength of 2‒5 MPa. Conclusion ·Dual-unit cantilever restorations supported by a single narrow-diameter implant may represent a viable treatment option for consecutive missing teeth in the anterior mandibular region.

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