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    Chinese expert consensus on ultrasound-guided nerve blocks in children (2025 edition)
    Writing Group of Chinese Expert Consensus on Ultrasound-Guided Pediatric Nerve Blocks in Children (2025 edition)
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (9): 1079-1098.   DOI: 10.3969/j.issn.1674-8115.2025.09.001
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    Ultrasound-guided nerve blocks in children have made significant progress in recent years, with improved safety and efficacy attributed to high-resolution ultrasound visualization. The widespread clinical adoption of ultrasound technology empowers clinicians to visualize pediatric neural structures and adjacent tissues clearly and individually, which permits real-time observation of local anesthetic spread, thereby markedly lowering complication risks inherent to conventional blind puncture techniques. This expert consensus is based on evidence-based medicine and clinical practical experiences, integrating the development history and current status of ultrasound-guided pediatric nerve blocks. It systematically elaborates on the anatomical characteristics of pediatric nerves and their impact on blocking techniques, clarifies the indications and contraindications for pediatric nerve blocks, and standardizes equipment preparation, drug formulation, and pediatric sedation protocols prior to nerve block administration. It also comprehensively provides the procedural guidance and technical key points for nerve blocks in different regions, including probe selection, needle insertion pathways, and real-time monitoring of local anesthetic diffusion, and analyzes the potential complications along with corresponding prevention and management strategies. Through in-depth discussions among the expert group, recommendations were formed based on jointly established criteria. The final consensus aims to provide practical guidance for the implementation of ultrasound-guided pediatric nerve blocks in clinical anesthesia and pain management, thereby promoting more effective and safer application, ultimately achieving the goal of reducing children's pain and accelerating postoperative recovery.

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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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    Pathogenic mechanisms and therapeutic advances of small colony variants
    LIANG Xiaoning, SHI Tingwang, CHEN Yunfeng
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (6): 784-791.   DOI: 10.3969/j.issn.1674-8115.2025.06.014
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    Small colony variants (SCVs) are unique phenotypic variants produced by bacteria such as Staphylococcus aureus under environmental selective pressure, with specific biological characteristics, including slow growth, reduced pigment synthesis, auxotrophy, enhanced drug resistance, and easier intracellular colonization and biofilm formation. In recent years, it has been increasingly recognized that SCVs play a crucial role in the chronic progression of infections and poor prognosis. SCVs exhibit significant heterogeneity with complex and diverse molecular profiles. Compared with wild-type strains, SCVs have low virulence and significantly enhanced adherence, and they can effectively evade immune system recognition and clearance. SCVs invade host cells, including macrophages, and form dormant intracellular forms, causing antimicrobial resistance. These variants can revert to wild-type bacteria when environmental conditions improve, causing persistent and refractory infections such as osteomyelitis, cystic fibrosis, and implant-associated infections. However, current treatments for SCV-related infections are limited to long-term antibiotic therapy combined with debridement of infected tissue, and understanding of SCVs, their pathogenic mechanisms, and treatments remains limited. Traditional therapies, such as rifampicin combined with vancomycin, have limited efficacy against intracellular SCVs. Novel strategies, such as targeting ATP synthase inhibitors (eg. lycopene), using nanocarrier-delivered antibiotics to enhance intracellular penetration, alkalinizing of the microenvironment, or disrupting biofilms by physical therapies, are important breakthroughs in the fight against SCV-associated infections. This paper summarizes the biological characteristics, pathogenic mechanisms, and therapeutic progress of SCVs, providing reference for research and treatment of SCV-related infections.

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    Quantitative analysis of the distance between articular disc and condyle in patients with temporomandibular disorders
    SUN Lei, DAI Shifeng, CHEN Yuhua, XU Xinyi, JIANG Kele, LI Xiaowen, LI Chengjing, WU Tingting
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (6): 684-692.   DOI: 10.3969/j.issn.1674-8115.2025.06.003
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    Objective ·To evaluate the relationships between disc-condyle distance and anterior disc displacement, as well as between disc-condyle distance and disc morphology, in patients with temporomandibular disorders (TMD) using magnetic resonance imaging (MRI) of the temporomandibular joint (TMJ). Methods ·From September 2023 to March 2024, 90 patients (180 TMJs) who visited the TMJ clinic of Department of Stomatology, The Second Affiliated Hospital of Anhui Medical University, with clinical symptoms of TMD and were diagnosed via MRI with either anterior disc displacement or no significant displacement, were included. Clinical data were collected, and MRI images were used to measure the angle of disc displacement, disc-condyle distance, disc length, and thickness. The degree of disc deformation was assessed. The relationships between clinical symptoms and anterior disc displacement, between anterior disc displacement and both disc morphology and disc-condyle distance, and between disc-condyle distance and disc morphology were analyzed. Results ·Among the 90 patients, there were 16 males and 74 females, with a mean age of (28.1±14.5) years. Among the 180 TMJs, 175 had clinical symptoms and 5 were asymptomatic. There were 40 joints with no displacement, 78 with reducible anterior disc displacement, and 62 with irreducible anterior disc displacement. In the joints with irreducible anterior disc displacement, the proportion of those with two or more symptoms was slightly higher at 62.9%, but the difference was not statistically significant compared with the joints with no displacement or reducible anterior disc displacement. MRI assessment revealed that in the joints with irreducible anterior disc displacement, the proportion of disc deformation type Ⅲ or higher was significantly higher compared with the non-displaced joints (P<0.001). The disc length was significantly shorter (P<0.001), and the intermediate zone thickness was significantly greater (P<0.001) compared with the non-displaced joints. The disc displacement angles at centric closure and maximum opening were also significantly larger (P<0.001). The disc-condyle distance was 3.10 (2.70, 3.70) mm for non-displaced joints, 3.40 (3.00, 4.00) mm for joints with reducible anterior disc displacement, and 6.60 (4.78, 7.90) mm for joints with irreducible anterior disc displacement, with significant differences (P<0.001). The disc-condyle distance was 3.10 (2.80, 3.60) mm for type Ⅰ discs, 3.70 (3.10, 4.60) mm for type Ⅱ discs, 5.10 (4.00, 7.30) mm for type Ⅲ discs, and 6.80 (4.98, 8.20) mm for type Ⅳ/Ⅴ discs, with significant differences (P<0.001). The disc-condyle distance was negatively correlated with disc length (rs=-0.469, P<0.001), positively correlated with intermediate zone thickness (rs=0.319, P<0.001), and positively correlated with disc displacement angle at centric closure (rs=0.626, P<0.001). Conclusion ·With increasing severity of disc deformation, intermediate zone thickness, and disc displacement angle at centric closure, as well as decreasing disc length, the disc-condyle distance increases. The disc-condyle distance is an important indicator for MRI assessment of pathological changes in TMD.

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    Research on the improvement of cognitive impairment, endoplasmic reticulum stress and neuroinflammation in Alzheimer's disease by emodin
    YANG Le, ZHOU Yi, WANG Keyun, LAI Yali
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (6): 727-734.   DOI: 10.3969/j.issn.1674-8115.2025.06.007
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    Objective ·To explore the effects and potential mechanisms of emodin on Alzheimer's disease (AD). Methods ·Wild-type C57BL/6J mice and 3×Tg-AD mice were divided into 6 groups: Control group (C57BL/6J mice), AD group (3×Tg-AD mice), Emodin 25 mg/kg group (3×Tg-AD mice + Emodin 25 mg/kg), Emodin 50 mg/kg group (3×Tg-AD mice + Emodin 50 mg/kg), Emodin 100 mg/kg group (3×Tg-AD mice + Emodin 100 mg/kg) and Donepezil group (3×Tg-AD mice + Donepezil 3 mg/kg). The Morris water maze test was used to evaluate the learning and memory abilities of mice. The expression of glial fibrillary acidic protein (GFAP), glucose-regulated protein 78kDa (GRP78), and inositol-requiring enzyme 1α (IRE1α) was detected by immunohistochemistry. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 in brain tissue were measured by enzyme-linked immunosorbent assay (ELISA). Western blotting was used to detect the expression of NF-κB p65, p-NF-κB p65, p38, and p-p38 proteins. Results ·Compared with the control group, mice in the AD group showed impaired cognition, increased GFAP expression, elevated levels of TNF-α, IL-1β and IL-6, and increased expression of GRP78 and IRE1α, along with enhanced phosphorylation of NF-κB p65 and p38. Compared with the AD group, emodin improved cognitive impairment of AD mice, inhibited astrocyte overactivation and neuroinflammation, and decreased the expression of GRP78, IRE1α, phosphorylated NF-κB p65, and phosphorylated p38 in brain tissue. Conclusion ·Emodin can effectively improve cognitive impairment in AD mice, which may be related to the inhibition of endoplasmic reticulum stress-mediated neuroinflammation in astrocytes.

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    Preliminary study on early warning value and mechanism of interleukin-1β in extremely severe oral and maxillofacial space infections
    ZHU Hanyi, SHI Huan, YU Chuangqi, ZHENG Lingyan
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (6): 661-672.   DOI: 10.3969/j.issn.1674-8115.2025.06.001
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    Objective ·To investigate the role of interleukin-1β (IL-1β) in predicting the severity of oral and maxillofacial space infection (OMSI), and to explore the key mechanisms regulating IL-1β release, the critical immune cell subpopulations involved, and the intercellular communication networks among immune cells in OMSI patients. Methods ·A total of 62 OMSI patients admitted to the Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, from January to November 2023 were enrolled, including 20 patients with moderate infection, 21 with severe infection, and 21 with extremely severe infection. Logistic regression analysis was performed to identify risk factors for extremely severe infection, and receiver operating characteristic (ROC) curves were constructed to evaluate the ability of the above indicators to predict extremely severe infection. Peripheral blood mononuclear cells (PBMCs) from 2 patients in each group (moderate, severe and extremely severe) and 2 healthy controls (GSE224198) were analyzed using single-cell RNA sequencing (scRNA-seq) to identify key pro-inflammatory cell subtypes and genes, and to examine their changing trends with increasing infection severity. Cell-cell communication was assessed using CellChat. Quantitative real-time polymerase chain reaction (qPCR) and Western blotting were used to validate inflammasome activation levels in PBMCs. Results ·Compared with patients with moderate and severe infections, levels of procalcitonin (PCT) (P<0.05) and IL-1β (P<0.05) were significantly elevated in patients with extremely severe infection. Logistic regression identified IL-1β as an independent risk factor for extremely severe infection (OR=1.814, 95% CI 1.256‒2.621, P=0.002). The area under the ROC curve (AUC) for the combined prediction of extremely severe infection using IL-1β and PCT was 0.943. scRNA-seq revealed continuous upregulation of NLRP3 (NOD-like receptor family pyrin domain-containing 3) and IL1B gene expression in monocytes as infection severity increased, with intermediate monocytes being the main IL1B-expressing cell subtype. IL-1Β-IL-1R signaling, C-C motif chemokine ligand (CCL) and intercellular adhesion molecule (ICAM) signaling were significantly enhanced in monocytes. Macrophage migration inhibitory factor (MIF) signaling between T cells and monocytes also increased notably. With infection progression, the mRNA levels of NLRP3 and IL1B in peripheral blood rose steadily, and the protein levels of NLRP3, caspase-1 p20, apoptosis-associated speck-like protein containing a CARD (ASC) and IL-1β were persistently elevated. Conclusion ·The combined levels of IL-1β and PCT at admission can effectively predict extremely severe OMSI. NLRP3 inflammasome activation is observed in PBMCs of OMSI patients. The elevation of IL-1β is closely associated with intermediate monocytes. Monocyte-mediated IL-1Β-IL-1R, CCL and ICAM signaling pathways, along with T cell-mediated MIF signaling pathways, collectively promote the inflammatory response.

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    Research status of ultrasound parameters and blood indicators in predicting fetal growth restriction
    LIANG Shuyuan, YE Baoying, CHENG Weiwei
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (8): 1059-1065.   DOI: 10.3969/j.issn.1674-8115.2025.08.014
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    Fetal growth restriction (FGR) refers to the failure of a fetus to reach the level of growth potential determined by its genetic potential. It is a common obstetric complication, occurring in 5% to 10% of pregnancies. As a major risk factor for perinatal death and adverse neonatal outcomes, early prediction of FGR is crucial for optimizing pregnancy management. Existing evidence suggests that FGR is significantly associated with a variety of adverse pregnancy outcomes, including intrauterine hypoxia, preterm birth, neonatal asphyxia, and even neonatal mortality. It may also affect long-term neurological development and increase the risk of metabolic diseases in adulthood. Its pathogenesis is complex, which may involve placental blood flow perfusion insufficiency and genetic factors. Ultrasound parameters are the main basis for the diagnosis of FGR, among which fetal biological and hemodynamic parameters are of great value. Elevated umbilical artery blood flow resistance index, absent or reversed end-diastolic blood flow, and placental insufficiency are associated with the severity of FGR. However, approximately 10% of fetuses diagnosed by ultrasound as having FGR are later confirmed to be healthy small-for-gestational-age (SGA) infants after birth, and this false positive result may lead to unnecessary clinical interventions. Currently, there is no recognized accurate prediction model for FGR in clinical practice. Future research should focus on establishing unified diagnostic criteria and developing multi-index joint prediction tools based on artificial intelligence (AI). Early prediction and intervention for FGR are of great significance to improve perinatal outcomes. This paper reviewed the predictive value of ultrasound parameters, blood indicators, and their integration with AI for FGR, in order to provide a basis for clinical decision-making.

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    Systematic analysis and exploration of single-cell transcriptomes in aortic aneurysm
    ZHANG Xingyu, LI Ruogu
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (6): 735-744.   DOI: 10.3969/j.issn.1674-8115.2025.06.008
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    Objective ·To explore the single-cell landscape of aortic aneurysm (AA) utilizing single-cell RNA sequencing (scRNA-seq) technology. Methods ·A systematic search of the Gene Expression Omnibus (GEO) was conducted to collect all datasets meeting the inclusion criteria. Changes in the percentage of cellular composition of AA tissues versus normal control tissues were analyzed using R language and the Seurat package. Cell-cell interactions were assessed by gene expression levels of cellular receptor-ligand pairs using the CellChat package. Cellular senescence was scored and compared based on the SenMayo Senescence gene set using the AUCell package.Single-cell transcriptional data were simulated as traditional transcriptome data for differential gene screening and gene pathway enrichment analysis of pericytes. Results ·A total of nine datasets meeting the criteria were included. After quality control and merging, RNA count data for 104 570 cells were obtained, comprising 48 311 in the control group and 56 259 in the AA group. Cells were categorized into 19 clusters and annotated into 14 cell types. Compared with the control group, the proportion of pericytes in the AA group significantly decreased (P<0.001), while the proportions of monocytes/macrophages and dendritic cells increased (P=0.020, P=0.045). The number of intercellular interactions in the AA group was markedly higher than that in the control group; however, yet the interactions involving smooth muscle cells decreased, and the interaction intensity among pericytes diminished. There were 5 unique intercellular interactions in the control group and 13 unique interactions in the AA group, with the interaction involving SPP1 showing the highest relative information flow. Except for adipocytes, all cell types in the AA group exhibited significantly higher senescence scores (P<0.001), with an overall increase in the number of senescent cells (P<0.001), predominantly fibroblasts. Differential expression analysis of pericytes showed 185 upregulated genes and 151 downregulated genes in the AA group, with Spp1 exhibiting the highest upregulation. Pro-inflammatory pathways related to chemokine activity and CXC chemokine receptor binding were significantly enriched. Conclusion ·The cellular composition in AA tissues undergoes significant alterations, characterized by an increase in intercellular interactions and elevated levels of cellular senescence, with Spp1 identified as a key gene.

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    Clinicopathologic characteristics, gene mutation profile, and prognostic analysis of diffuse large B-cell lymphoma with lung involvement
    CHEN Siyuan, SHI Qing, FU Di, WANG Li, CHENG Shu, XU Pengpeng, ZHAO Weili
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (9): 1214-1220.   DOI: 10.3969/j.issn.1674-8115.2025.09.013
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    Objective ·To investigate the clinicopathologic features, gene mutation profile, and real-world survival prognosis of diffuse large B-cell lymphoma (DLBCL) with pulmonary involvement. Methods ·The clinical data of 110 patients with newly diagnosed, pathologically confirmed DLBCL and pulmonary involvement at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, between August 2003 and December 2022 were retrospectively collected and analyzed. Evaluation of the efficacy of treatment, survival analyses, and univariate and multivariate analyses were performed in 88 patients who received a first-line regimen based on rituximab in combination with cyclophosphamide, doxorubicin/epirubicine, vincristine, and prednisone (R-CHOP). A total of 74 patients underwent targeted DNA sequencing of 55 lymphoma-related genes and were evaluated for mutations. Results ·Among the 110 patients, 72 (65.5%) were >60 years old, 52 (47.3%) were female, 92 (83.6%) presented with Ann Arbor stage Ⅲ‒Ⅳ, 20 (18.2%) had ECOG scores≥2, 75 (68.2%) had elevated lactate dehydrogenase (LDH) levels, 79 (71.8%) had ≥2 extranodal involvements, 32 (31.4%) were classified as germinal center B-cell subtype, 22 (26.8%) were diagnosed with double expressor lymphoma, and 4 (4.6%) with double-hit lymphoma. Among the patients treated with R-CHOP-based first-line regimens, the objective response rate (ORR) was 68.2%, the 5-year progression-free survival (PFS) rate was 43.7%, and the 5-year overall survival (OS) rate was 65.4%. Univariate analysis showed that elevated LDH and ECOG score≥2 were poor prognostic factors for PFS and OS, and mutations in PIM1 and CD79B were poor prognostic factors for PFS among high-frequency mutations. Multivariate analysis showed that elevated LDH was an independent adverse prognostic factor for PFS (HR=2.47, 95%CI 1.28‒4.77) and OS (HR=2.71, 95%CI 1.21‒6.07). Targeted sequencing results showed that PIM1 (25.7%), MYD88 (24.3%), TP53 (18.9%), CD79B (17.6%), KMT2D (17.6%), and TNFAIP3 (16.2%) were the high-frequency mutations with mutation rates over 15%. Conclusion ·Elevated LDH is an independent adverse prognostic factor for PFS and OS in DLBCL with pulmonary involvement. Mutations in PIM1, MYD88, TP53, CD79B, KMT2D, and TNFAIP3 are frequently observed in this population.

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    Microenvironmental profiles of wound tissues with accelerated healing properties by HAMA hydrogel
    JIANG Qianyu, YAO Chengcheng, JI Ping, WANG Ying
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (8): 969-980.   DOI: 10.3969/j.issn.1674-8115.2025.08.004
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    Objective ·To explore the roles of hyaluronic acid methacryloyl (HAMA) hydrogel in skin wound healing and to characterize the microenvironmental landscape at wound sites. Methods ·A full-thickness skin excision model was established in mice, which were randomly divided into a control group (n=3) and a HAMA group (n=3). The wound in the HAMA and control groups were covered with 100 μL of HAMA hydrogel and 100 μL of phenyl-2,4,6-trimethylbenzoylphosphonic acid lithium (LAP), respectively. Both groups were then irradiated with a UV lamp for 20 s. The residual wound areas was measured on days 0, 3, 7, 10, and 14. Wound healing effects of HAMA hydrogel were analyzed by measuring the residual wound area and through H-E staining. Single-cell RNA sequencing technology was utilized to analyze the cellular profile of local wound skin tissues at day 14 post-injury. Immunofluorescence assay was used to detect the levels of type I collagen, type Ⅲ collagen, F4/80, CD206, and CD86 in the wound sites. The mRNA expression levels of Arg1, Nos2, Itgam, and Itgb2 in the mouse macrophage cell line Raw264.7 co-cultured with HAMA hydrogel for 24 h were detected by RT-qPCR. The fibroblasts and macrophages in the local skin of the mouse wound on day 14 were analyzed using the Seurat package, and the communication between fibroblasts and macrophages was analyzed using the CellChat package. Results ·Mice treated with HAMA hydrogel exhibited a significantly faster rate of wound healing process compared to the control group. At day 14, wounds in the HAMA-treated mice had already healed, while those in the control group remained unhealed. Single-cell RNA sequencing analysis revealed a remarkable increase in the proportion of fibroblasts in the skin tissues of HAMA-treated wounds. The proportion of the Col3a1-high-expressing fibroblast subset increased (90.2%) compared to the control group (79.8%), while the proportion of the Col1a1-high-expressing fibroblast subset decreased (5.7% vs 15.9%). Immunofluorescence analysis confirmed that the level of type Ⅲ collagen in the wound tissues of the HAMA group was significantly higher than that in the control group (P=0.035), while the level of type Ⅰ collagen was significantly lower (P=0.044). Although there was no significant difference in the proportions of macrophages in the wound tissues between the HAMA-treated and control groups, scRNA sequencing data and in vitro experiments using Raw264.7 cells showed that HAMA hydrogel could induce the expression of Arg1 and decrease the expression of Nos2 in the macrophages (P<0.001). Additionally, macrophages in the HAMA-treated wounds expressed higher levels of CD206 and lower levels of CD86 (P=0.042, P=0.011). The results of the CellChat analysis showed that, compared to the control group, increased communication intensity was observed between macrophages and fibroblasts subsets at the wound sites in the mice of HAMA group. Conclusion ·The microenvironment after HAMA hydrogel treatment is conducive to skin wound healing, characterized by a local aggregation of anti-inflammatory macrophages and fibroblasts that secrete type Ⅲ collagen.

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    Molecular epidemiology of Klebsiella pneumoniae isolated from children
    JIANG Jie, ZHANG Hong, LUN Heyuan, PAN Fen, YU Fangyuan, HE Ping
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (8): 1027-1034.   DOI: 10.3969/j.issn.1674-8115.2025.08.010
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    Objective ·To analyze the molecular epidemiological characteristics of Klebsiella pneumoniae isolated from children, including the distribution of serotypes, resistance genes, and virulence genes, to provide a scientific basis for the prevention and treatment strategies of Klebsiella pneumoniae infections in children. Methods ·A total of 133 non-duplicate strains of Klebsiella pneumoniae clinically isolated from Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, from April 2023 to April 2024, were collected. Antimicrobial susceptibility testing was performed by using the Vitek-2 Compact system. Capsular polysaccharide K antigen serotypes (K types) were determined by wzy-dependent initiator (wzi) gene sequencing. Resistance genes were detected by the colloidal gold method. Virulence genes and lipopolysaccharide O antigen serotypes (O types) were identified by PCR method. Results ·Among the 133 strains of Klebsiella pneumoniae, a total of 50 strains of carbapenem-resistant Klebsiella pneumoniae (CRKP) were detected, mainly distributed in the neonatal ward and intensive care unit (ICU). CRKP exhibited high resistance to most antimicrobial agents, and the main type of carbapenemase gene was blaNDM (34/50, 68.00%), followed by co-carriage of blaNDM+blaOXA-48 (10/50, 20.00%) and blaKPC (6/50, 12.00%). Serotype analysis revealed that the 50 CRKP strains could be divided into 8 K types and 6 O types. The most common K type was KL17 (30/50, 60.00%), followed by KL105 (10/50, 20.00%) and KL47 (5/50, 10.00%). The most common O type was O4 (30/50, 60.00%), followed by O3b (7/50, 14.00%, ), O3/O3a (6/50, 12.00% ), and OL101 (5/50, 10.00%). Significant correlations were identified between KL47 and OL101 serotypes (KL47:OL101), between KL17 and O4 serotypes (KL17:O4), and between KL1/KL2 and O1 serotypes (KL1/KL2:O1). Conclusion ·The CRKP strains infecting children primarily carry blaNDM-type carbapenemase genes, showing a significant difference compared to CRKP-infected adults. The detection rate of CRKP in the neonatal ward is significantly higher than those in other departments, suggesting that infection prevention and control measures in this ward need to be strengthened.

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    Experimental study on novel pH-responsive manganese-based nanoprobes for ferroptosis and magnetic resonance imaging in breast cancer
    WANG Jingyi, DENG Jiali, ZHU Yi, DING Xinyi, GUO Jiajing, WANG Zhongling
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (9): 1183-1193.   DOI: 10.3969/j.issn.1674-8115.2025.09.010
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    Methods ·BSA-MnO2@CPT (BMC) nanoprobes were prepared by biomineralization, and their physicochemical properties were characterized by transmission electron microscope (TEM) and dynamic light scattering. The magnetic resonance imaging (MRI) was used to evaluate the pH-responsive MRI T1 activation and time-dependent activation efficacy at the cellular level, with quantitative analysis of MRI T1 signal intensity. The reactive oxygen species (ROS) generation and glutathione (GSH) depletion by BMC nanoprobes were respectively detected by methylene blue (MB) and DTNB in vitro. The synergistic efficacy of chemotherapy and ferroptosis mediated by the nanoprobes in 4T1 breast cancer cells was evaluated using the Thiazolyl Blue Tetrazolium Bromide (MTT) assay. After co-incubation 4T1 cells with BMC, intracellular ROS levels were determined through the staining of ROS fluorescence indicator 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) and the level of lipid peroxide (LPO) expression was detected by using BODIPY581/591 C11 probe. A subcutaneous xenograft tumor model of 4T1 breast cancer was established in mice, with four experimental groups: Control group (PBS group), CPT group, BSA-MnO2(BM) group, and BMC group. The pH-responsive T1 activation effect of the BMC nanoprobes was dynamically monitored in vivo, while the ferroptosis-based antitumor efficacy was evaluated by measuring tumor volume and ferroptosis biomarkers (LPO and ROS). Results ·TEM revealed that the prepared BMC nanoprobes exhibited a spherical morphology with an average diameter of approximately 150 nm. The MRI results demonstrated that the nanoprobes were pH-activable, exhibiting progressively enhanced T1 signal intensity under acidic conditions, and displaying pH-dependent r1 relaxivity enhancement. These findings validated their dual pH/time-responsive activation efficacy at the cellular level. In vitro solution-level MB and DTNB assays demonstrated that the BMC nanoprobes effectively enhanced the generation of ROS and the consumption of GSH. Fluorescence staining with DCFH-DA and BODIPY581/591 C11 demonstrated that the combination of ferroptosis effect and chemotherapy significantly enhanced intracellular generation of ROS and LPO accumulation. The MTT assay demonstrated that the survival rate of tumor cells significantly decreased to 17% (P=0.003). In vivo MRI demonstrated that the T1 signal was significantly enhanced and reached its peak at 4 h after tail vein injection of the BMC nanoprobes. Furthermore, in vivo antitumor therapy showed that the BMC group exhibited upregulated levels of LPO and ROS in tumor tissues, accompanied by marked tumor suppression (P=0.009). Conclusion ·The pH-responsive theranostic BMC nanoprobes enhances antitumor efficacy via the synergistic interaction of chemotherapy and ferroptosis, while enabling tumor microenvironment-activated MRI. Objective· To construct a pH-responsive manganese-based nanoprobe and explore the therapeutic efficacy of chemotherapy/ferroptosis synergistic treatment in breast cancer and the effect of pH-responsive magnetic resonance-activated imaging.

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    Clinical analysis and literature integration study of cystic fibrosis complicated by allergic bronchopulmonary aspergillosis
    HE Chen, YAN Silei, ZHOU Weitao, LING yong, YU Ningning, JIANG Kun, QIAN Liling
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (8): 1066-1073.   DOI: 10.3969/j.issn.1674-8115.2025.08.015
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    Objective ·To explore the diagnostic and treatment methods for patients with cystic fibrosis (CF) complicated by allergic bronchopulmonary aspergillosis (ABPA), and to enhance clinicians' understanding of these two diseases. Methods ·A retrospectively analysis was conducted on the clinical data of 5 patients with CF complicated by ABPA admitted to the Department of Respiratory Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, from July 2023 to August 2024. A literature search was performed in PubMed, Web of Science, Cochrane Library, and CNKI for studies published in the past 10 years regarding the co-existence of these diseases. Clinical manifestations, treatment courses, and current epidemiological research were summarized and analyzed. Results ·Common symptoms of patients with CF complicated by ABPA included aggravated cough and expectoration, wheezing, fever, and dyspnea. Whole-exome aequencing indicated mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and an increase in the concentration of chloride ions in sweat. The levels of total serum immunoglobulin E (IgE) and Aspergillus fumigatus-specific IgE increased, and chest computed tomography (CT) showed bronchiectasis and mucus plugging. CF complicated by ABPA is often missed or misdiagnosed for asthma. In China, ABPA is often diagnosed before CF, whereas in Caucasian populations CF is typically diagnosed first. Initial treatment usually involves long-term oral administration of antifungal drugs such as voriconazole combined with glucocorticoids such as prednisone. For patients with frequent relapses or severe side effects, alternative antifungal agents or omalizumab therapy may be considered. Co-infection with Pseudomonas aeruginosa is common, often requiring intravenous antibiotics such as cefoperazone-sulbactam. Current epidemiological research focuses mainly on clinical characteristics, treatment regimens, and novel diagnostic methods. Conclusion ·ABPA and CF have overlapping symptoms. Accurate diagnosis of CF complicated by ABPA requires genetic testing, sweat chloride measurement, chest CT, and serological tests. The coexistence of these diseases often leads to missed, delayed, or incorrect diagnosis, increasing patient burden. Present epidemiological studies mainly address clinical characteristics with a lack of targeted clinical drug trials for this patient population.

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    Research progress on immune cell therapy in renal cell carcinoma
    CHEN Zixuan, LIU Min
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (7): 916-925.   DOI: 10.3969/j.issn.1674-8115.2025.07.014
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    Renal cell carcinoma (RCC) is the most common type of malignant kidney tumor in adults, accounting for more than 90% of all renal malignancies. In its early stages, RCC is often asymptomatic and is frequently discovered incidentally during physical examinations or diagnostic imaging. While localized RCC can often be effectively treated with surgical resection, the prognosis for advanced or metastatic cases remains poor, as conventional therapies such as chemotherapy, radiotherapy, and targeted therapy often show suboptimal responses. As a highly immunogenic tumor, RCC is capable of evading immune surveillance through various mechanisms. Therefore, immune therapies, especially cell-based therapies at the forefront, have gained significant attention in recent years as emerging treatment modalities, showing great potential. Immune cell therapy enhances anti-tumor immune responses by utilizing the patient's immune system or exogenous immune cells to restore immune function, thereby effectively eliminating tumor cells. It has become an important research direction for RCC treatment. However, despite its promising clinical prospects, immune cell therapy still faces numerous challenges. Issues such as individual heterogeneity, immune-related adverse events, immune suppression in the tumor microenvironment, and post-treatment drug resistance continue to affect its clinical efficacy. This review summarizes the immune escape mechanisms in RCC, outlines the progress of RCC immune cell therapy, and analyzes its future prospects, aiming to provide insights and direction for better addressing the clinical challenges of refractory RCC.

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    Research progress in effects and mechanisms of dietary pattern interventions in metabolic associated fatty liver disease
    SONG Jing, JIANG Shuo, WAN Fangyu, LI Juan, MUHETA Adina, MIN Xinying, ZHOU Jingqi
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (7): 926-933.   DOI: 10.3969/j.issn.1674-8115.2025.07.015
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    Metabolic associated fatty liver disease (MAFLD) is a type of fatty liver disease associated with systemic metabolic disorders, and its prevalence has been increasing year by year, becoming a major challenge to global public health. The development of MAFLD is associated with various factors, including obesity, dyslipidemia, diabetes and other factors. Excessive body fat, particularly increased visceral adiposity, contributes to hepatic fat accumulation. Abnormal blood lipid levels can also disrupt liver fat metabolism. The risk of MAFLD in patients with diabetes is greatly increased due to insulin resistance and other problems. Dietary interventions are considered an effective strategy for the prevention and treatment of MAFLD. In recent years, several dietary patterns, such as low-carbohydrate diets, intermittent fasting, and the Mediterranean diet, have been applied in clinical practice. Their primary mechanisms include reducing oxidative stress, regulating gut microbiota, and inducing fat autophagy. However, the responses to different dietary patterns vary among individuals due to differences in genes, lifestyle, and disease severity. Therefore, systematically evaluating the effects and mechanisms of these dietary patterns in the prevention and treatment of MAFLD has significant clinical importance. This review compares the effects of different dietary patterns on improving liver function, hepatic fat content, blood glucose, and lipid levels, and analyzes their underlying mechanisms of intervention, to explore how to select personalized dietary strategies based on individual differences. It is intended to provide new insights for the precise prevention and treatment of MAFLD, thereby improving patients′ outcomes and alleviating the burden on public health.

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    Advances in the treatment of pediatric B-cell acute lymphoblastic leukemia with high-risk cytogenetics
    TANG Junqian, LI Benshang
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (10): 1390-1399.   DOI: 10.3969/j.issn.1674-8115.2025.10.015
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    B-cell acute lymphoblastic leukemia (B-ALL) is one of the most common pediatric malignancies, characterized by highly heterogeneous genetic alterations. The precise identification of high-risk genetic abnormalities, such as BCR-ABL1, KMT2A rearrangement, and TCF3-HLF, plays a crucial role in risk stratification, the formulation of chemotherapy regimens, and the selection of individualized therapies. High-risk cytogenetics can profoundly impact the trajectory of disease progression and therapeutic outcomes. Regarding therapy, the refinement of treatment strategies through precise molecular classification and risk stratification has catalyzed a gradual paradigm shift in clinical practice. This transition moves away from the traditional reliance on conventional chemotherapy agents toward individualized pharmacotherapy and disease management strategies based on prognostic risk stratification. In recent years, immunotherapy has achieved significant progress in leukemia treatment. Chimeric antigen receptor T-cell (CAR-T) therapy and monoclonal antibodies have emerged as novel therapies for patients with relapsed/refractory (R/R) B-ALL harboring high-risk cytogenetic features. These innovations have significantly improved the prognosis for this patient population. Currently, new clinical trials are continuously advancing. Emerging targeted therapies and cell therapies represented by CAR-T cells have become hot spots of current research and have demonstrated remarkable development potential. This review synthesizes recent therapeutic advances across pediatric B-cell acute lymphoblastic leukemia subtypes harboring high-risk genetic abnormalities, with a focused emphasis on the evolving role of immunotherapy. By critically integrating current evidence, we aim to outline rational strategies for developing safer and more effective therapies that can meaningfully improve clinical outcomes in these high-risk children and adolescents.

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    Effect of Th17-specific Stat3 knockout on anxiety- and depressive-like behaviors in periodontitis mice
    ZHOU Yining, YE Zhiyun, CHEN Huiwen, XIE Xinyi, ZHOU Wei, SONG Zhongchen
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (7): 838-845.   DOI: 10.3969/j.issn.1674-8115.2025.07.005
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    Objective ·To investigate the effect of Th17 cell-specific Stat3 knockout on anxiety- and depressive-like behaviors. Methods ·Mice with specific Stat3 knockout in Th17 cells (Stat3fl/fl; Il17a-CreERT2), named Stat3Il17a , and wild-type mice (Stat3fl/fl, WT) were generated through the Cre/LoxP system, and Stat3 knockout was induced by intraperitoneal injection of tamoxifen. CD4+T cells were isolated using magnetic-activated cell sorting and induced to differentiate into Th17 cells. Reverse transcription polymerase chain reaction and Western blotting were used to verify Stat3 knockout efficiency. Mice were assigned into 4 groups: WT-C group, Stat3Il17a -C group, WT-P group, and Stat3Il17a -P group. The periodontitis model was established in the WT-P group and the Stat3Il17a -P group by injection of Porphyromonas gingivalis-lipopolysaccharide (P. gingivalis-LPS) into the gingival sulcus. Behavioral tests, including the open field test, elevated zero maze, and forced swimming test, were conducted to evaluate changes in anxiety- and depressive-like behaviors. Micro-computed tomography was used to observe destruction of alveolar bone. Neuronal injury was observed by H-E staining, and the level of brain-derived neurotrophic factor (BDNF) was detected by enzyme-linked immunosorbent assay. Results ·mRNA expression and protein levels of Stat3 in Stat3Il17a mice were inhibited compared to WT mice (P<0.05). Experimental periodontitis model was successfully established in the WT-P group and the Stat3Il17a -P group. The degree of alveolar bone destruction was reduced in the Stat3Il17a -P group compared to the WT-P group. In the WT-P group, decreased residence time in the central area and in the open area was observed in the open field test and elevated zero maze respectively, and increased immortal time was recorded in the forced swimming test (P<0.05). Moreover, neuronal injury was detected and significantly decreased expression levels of BDNF in the brain were measured in the WT-P group compared with the WT-C group (P<0.05). The degree of abnormal behaviors and neuronal injury was reduced in the Stat3Il17a -P group compared to the WT-P group (P<0.05). Moreover, the level of BDNF in the Stat3Il17a -P was higher than that in the WT-P group (P<0.05). Conclusion ·Periodontitis may contribute to anxiety- and depressive-like behaviors and neuronal damage in mice, while Th17-specific conditional knockout of Stat3 could significantly alleviate pathological behaviors and neuronal damage. Stat3-mediated-Th17 cell immune responses may play a crucial role in the correlation between periodontitis and anxiety and depression.

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    HENMT1 promotes the proliferation and migration of gastric cancer by activating the PI3K-AKT-mTOR signaling pathway
    YANG Na, LIU Junli, BAI Jing, YANG Siyi, HAN Jiming, ZHANG Huahua
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (6): 717-726.   DOI: 10.3969/j.issn.1674-8115.2025.06.006
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    Objective ·To investigate the role of HEN methyltransferase 1 (HENMT1) in the proliferation and migration of gastric cancer (GC) and its potential molecular mechanisms. Methods ·The expression of HENMT1 in GC was examined using bioinformatics databases, Western blotting and quantitative real-time PCR (qPCR). Kaplan-Meier Plotter and BEST online tools were used to analyze the correlations between HENMT1 expression and overall survival, perineural invasion, subtypes, tumor location and Lauren classification in clinical GC patients. GC cells were cultured in vitro and treated with small interfering RNA (siRNA) targeting HENMT1 and HENMT1 overexpression vectors, in combination with a PI3K activator (740 Y-P) or PI3K inhibitor (3-MA). The roles of HENMT1 in GC cell proliferation and migration were assessed using cell counting kit-8 (CCK-8) assay, colony formation assay, wound healing assay and Transwell migration assay. Results ·HENMT1 was significantly upregulated in GC and positively associated with perineural invasion. Its expression was closely related to GC subtypes, being most pronounced in the proliferative subtype, and was higher in intestinal-type GC according to the Lauren classification. However, HENMT1 expression showed no significant correlation with overall survival or tumor location (including gastric body, cardia, antrum and whole stomach). Functional experiments demonstrated that silencing HENMT1 inhibited GC cell proliferation and migration, whereas overexpression of HENMT1 enhanced these capabilities. Mechanistically, silencing HENMT1 reduced the levels of phosphorylated PI3K, AKT and mTOR, as well as their total protein expression. Conversely, HENMT1 overexpression upregulated these proteins. Moreover, siHENMT1 combined with the PI3K activator 740 Y-P effectively reversed the proliferation and migration effects induced by 740 Y-P, while overexpressed HENMT1 combined with the PI3K inhibitor 3-MA reversed the suppressive effects of 3-MA on GC cell proliferation and migration. Conclusion ·HENMT1 is highly expressed in GC and positively regulates the proliferation and migration of gastric cancer cells by activating the PI3K-AKT-mTOR signaling pathway.

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    Effect of preoperative chemotherapy combined with immunotherapy in a colorectal cancer patient with KRAS mutation
    JIANG Yi, HUANG Chenhao, LI Zhiliang, WU Junwei, ZHAO Ren, ZHANG Tao
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (9): 1256-1260.   DOI: 10.3969/j.issn.1674-8115.2025.09.018
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    Colorectal cancer (CRC), a highly prevalent malignant tumor worldwide, has shown a continuously increasing incidence, particularly with the rise of early-onset CRC in young populations. Neoadjuvant therapy, as an important strategy for locally advanced CRC, shows significant potential to downstage tumors, improve radical surgical cure rates, and enhance prognosis. In this paper, a 39-year-old male patient with sigmoid colon adenocarcinoma at clinical stage cT4aN2aM0 (stage ⅢC) is reported. Genetic testing revealed a mutation in the oncogene KRAS (G13D) and microsatellite stability (MSS). The patient also had significantly elevated carcinoembryonic antigen (CEA), lymph node metastasis, and suspected pelvic implant nodules, with a high risk of invasiveness and potential peritoneal metastasis. Because he had a refractory subtype of CRC with poor response to traditional immunotherapy, the patient was treated with neoadjuvant therapy, comprising CapeOx regimen (capecitabine+oxaliplatin), followed sequentially by sluzumab; after 6 treatment cycles, the tumor shrank significantly, and laparoscopic radical sigmoid colon resection was successfully performed, with no residual (ypT0N0) confirmed by postoperative pathology. This case suggests that for patients with KRAS-mutated MSS CRC resistant to traditional immunotherapy, a combination of CapeOx chemotherapy followed by programmed death-1 (PD-1) inhibitors may induce a deep pathological response and provide translational treatment opportunities for locally advanced patients. However, the universality and long-term benefits of this treatment regimen still require further longitudinal studies and clinical follow-up.

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    Clinicopathologic characteristics, gene mutation profile, and prognostic analysis of patients with adrenal diffuse large B-cell lymphoma
    HE Jiayin, CHEN Siyuan, SHI Qing, ZHANG Muchen, YI Hongmei, DONG Lei, QIAN Ying, WANG Li, CHENG Shu, XU Pengpeng, ZHAO Weili
    Journal of Shanghai Jiao Tong University (Medical Science)    2025, 45 (9): 1194-1201.   DOI: 10.3969/j.issn.1674-8115.2025.09.011
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    Objective ·To analyze the clinicopathologic characteristics, gene mutation profile, and prognostic factors of patients with adrenal diffuse large B-cell lymphoma (DLBCL). Methods ·From March 2002 to December 2022, a total of 105 patients with adrenal DLBCL admitted to Ruijin Hospital, Shanghai Jiao Tong University School of Medicine were retrospectively analyzed for their clinicopathological data, survival outcomes, and prognostic factors. Patients' gene mutation profiles were evaluated by targeted sequencing of 152 lymphoma-related genes. Results ·The median age of the patients was 62 (15‒82) years and the male-to-female ratio was 2.3∶1. Among them, 63 patients (60.0%) were over 60 years old, 22 patients (21.0%) had an Eastern Cooperative Oncology Group (ECOG) performance status of two or higher, 87 patients (82.9%) were staged Ann Arbor Ⅲ‒Ⅳ, 92 patients (87.6%) had elevated serum lactate dehydrogenase (LDH) levels (above the upper limit of reference), 84 patients (80.0%) had extranodal invasion in at least two organs, 67 patients (63.8%) were of non-germinal center B-cell (non-GCB) origin, and 95 patients (90.5%) had an international prognosis index (IPI) scored over 2. With a median follow-up of 28.3 (0.7‒191.9) months, the estimated 2-year overall survival (OS) rate and progression-free survival (PFS) rate were 68.3% and 53.1%, respectively. The estimated 5-year OS rate and PFS rate were 52.6% and 44.0%, respectively. Among 93 patients who could be evaluated for clinical outcomes, 62 (66.7%) got a complete response (CR). Univariate analysis and multivariate Cox analysis revealed that age over 60 years was an adverse prognostic factor for PFS, and ECOG performance status of two or higher was an adverse prognostic factor for both OS and PFS. Targeted gene sequencing in 46 adrenal diffuse DLBCL patients showed high mutation frequencies in lysine methyltransferase 2D (KMT2D; n=17, 37%), Pim-1 proto-oncogene, serine/threonine kinase (PIM1; n=17, 37%), MYD88 innate immune signal transduction adaptor (MYD88; n=15, 33%), CD79b molecule (CD79B; n=13, 28%), and BTG anti-proliferation factor 2 (BTG2; n=10, 22%). Conclusion ·Age over 60 years is an adverse prognostic factor for PFS, and ECOG performance status of two or higher is an adverse prognostic factor for both OS and PFS in patients with adrenal DLBCL. Patients exhibited high frequencies of KMT2D, PIM1, MYD88, CD79B, and BTG2 mutations, as well as an increased proportion of the MCD-like subtype.

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