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28 June 2025, Volume 45 Issue 6 Previous Issue    Next Issue
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Oral and maxillofacial surgery
Basic research
Clinical research
Evidence-based medicine
Techniques and methods
Review
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Oral and maxillofacial surgery

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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 2025, 45 (6):  661-672.  doi: 10.3969/j.issn.1674-8115.2025.06.001 Abstract ( 416 )   HTML ( 26 )   PDF (4921KB) ( 1290 )   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. Figures and Tables | References | Related Articles | Metrics

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Study on the effects of spermidine on LPS-induced inflammatory osteolysis in mouse calvaria ZHAO Xinyu, ZHANG Wenchao, CHEN Xuzhuo, SONG Jiaqi, HUANG Hui, ZHANG Shanyong 2025, 45 (6):  673-683.  doi: 10.3969/j.issn.1674-8115.2025.06.002 Abstract ( 348 )   HTML ( 15 )   PDF (11169KB) ( 1148 )   Objective ·To investigate the inhibitory effects of spermidine (SPD) on inflammatory osteolysis both in vivo and in vitro. Methods ·The CCK-8 assay was used to assess the viability of RAW264.7 macrophages treated with various concentrations of SPD. The levels of intracellular reactive oxygen species (ROS) in lipopolysaccharide (LPS)-activated RAW264.7 cells were evaluated by staining with dichlorodihydrofluorescein diacetate (DCFH-DA) and dihydroethidium (DHE), respectively. Reverse transcription real-time fluorescence quantitative PCR (RT-qPCR) was utilized to determine the effects of SPD on the expression of pro-inflammatory genes in LPS-activated RAW264.7 cells. Tartrate-resistant acid phosphatase (TRAP) staining was used to evaluate the effect of SPD on the differentiation of mouse primary bone marrow-derived macrophages (BMMs) into osteoclasts. RT-qPCR was employed to further analyze the effect of SPD on the expression of genes related to osteoclast differentiation and functions after BMM-induced differentiation. An LPS-induced mouse calvarial osteolysis model was constructed, and the therapeutic efficacy of SPD on inflammatory osteolysis was assessed using Micro-CT analysis, hematoxylin-eosin (H-E) staining and TRAP staining of histological sections. Results ·The CCK-8 assay showed that SPD, even at a concentration of 1 000 μmol/L, exhibited no significant cytotoxicity to RAW264.7 cells. ROS analysis revealed that SPD markedly inhibited LPS-induced elevation of intracellular ROS levels in macrophages. RT-qPCR results indicated that SPD suppressed the expression of pro-inflammatory genes induced by LPS. Both TRAP staining and RT-qPCR demonstrated that SPD effectively inhibited the differentiation of BMMs into osteoclasts induced by receptor activator of nuclear factor-κB ligand (RANKL) and reduced the expression of genes associated with osteoclast differentiation and function. In the mouse calvarial osteolysis model, Micro-CT analysis showed that the bone volume fraction and bone mineral density in the SPD-treated groups were significantly higher than those in the LPS group. Histological staining revealed that SPD treatment reduced inflammatory cell infiltration, decreased osteoclast numbers, and alleviated tissue damage. Conclusion ·SPD inhibits macrophage inflammatory responses and RANKL-induced osteoclast differentiation in vitro; in vivo, it alleviates LPS-induced inflammatory calvarial osteolysis in mice. Figures and Tables | References | Related Articles | Metrics

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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 2025, 45 (6):  684-692.  doi: 10.3969/j.issn.1674-8115.2025.06.003 Abstract ( 388 )   HTML ( 12 )   PDF (3843KB) ( 1229 )   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. Figures and Tables | References | Related Articles | Metrics

Basic research

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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 2025, 45 (6):  693-704.  doi: 10.3969/j.issn.1674-8115.2025.06.004 Abstract ( 511 )   HTML ( 21 )   PDF (7672KB) ( 1597 )   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. Figures and Tables | References | Related Articles | Metrics

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Study on the mechanism of KRAS R68G secondary mutation-induced resistance to KRASG12D-targeted inhibitor MRTX1133 WANG Gaoming, CUI Ran, LI Yanjing, LIU Yingbin 2025, 45 (6):  705-716.  doi: 10.3969/j.issn.1674-8115.2025.06.005 Abstract ( 339 )   HTML ( 9 )   PDF (6645KB) ( 1035 )   Objective ·To explore the mechanism at the atomic level by which the KRASG12D/R68G mutation induces tumor cell resistance to MRTX1133. Methods ·The crystal structure data of the KRASG12D-MRTX1133 complex were obtained from the RCSB Protein Data Bank (PDB). PyMOL software was used to mutate arginine at position 68 of KRAS to glycine (R68G), constructing the initial conformations of the KRASG12D-MRTX1133 and KRASG12D/R68G-MRTX1133 complexes. The LEaP module was used to build simulation systems under periodic boundary conditions. The ff19SB force field was applied to standard amino acids in KRAS, GAFF (general AMBER force field) to MRTX1133, and TIP3P (intermolecular potential three point) to water molecules. Energy minimization was performed using the Amber software suite. The systems were then heated to 300 K, followed by NVT (constant volume and temperature) equilibration and NPT (constant pressure and temperature) production. Root mean square deviation (RMSD), root mean square fluctuation (RMSF), principal component analysis (PCA) and solvent-accessible surface area (SASA) of MRTX1133 and GDP were analyzed using cpptraj. The number of hydrogen bonds between regions and the dynamic cross-correlation matrix (DCCM) of amino acid movements were also calculated. Results ·RMSD analysis showed greater structural variation in KRAS in the KRASG12D/R68G system compared to the KRASG12D system. RMSF analysis revealed significantly higher fluctuations in the Switch Ⅰ and Switch Ⅱ regions of the KRASG12D/R68G system. PCA indicated that Switch Ⅰ and Switch Ⅱ in the KRASG12D/R68G system were more frequently in an open conformation. The distances between Switch Ⅰ and the P-loop, and between Switch Ⅱ and the P-loop, were larger in the KRASG12D/R68G system, indicating an expanded binding pocket for GDP and MRTX1133 compared to the KRASG12D system. SASA analysis indicated that both GDP and MRTX1133 had increased solvent exposure in the KRASG12D/R68G system. DCCM analysis revealed more decoupled movements among the Switch Ⅰ, Switch Ⅱ and P-loop regions in the KRASG12D/R68G system. Conclusion ·The KRASG12D/R68G mutation disrupts the interactions between the Switch Ⅰ and Switch Ⅱ regions, leading to their separation and the opening of the MRTX1133 binding pocket. This increases the solvent exposure of MRTX1133, accelerates its dissociation, and ultimately results in KRASG12D/R68G resistance to MRTX1133. Figures and Tables | References | Related Articles | Metrics

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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 2025, 45 (6):  717-726.  doi: 10.3969/j.issn.1674-8115.2025.06.006 Abstract ( 312 )   HTML ( 17 )   PDF (7738KB) ( 956 )   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. Figures and Tables | References | Related Articles | Metrics

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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 2025, 45 (6):  727-734.  doi: 10.3969/j.issn.1674-8115.2025.06.007 Abstract ( 360 )   HTML ( 5 )   PDF (4800KB) ( 834 )   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. Figures and Tables | References | Related Articles | Metrics

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Systematic analysis and exploration of single-cell transcriptomes in aortic aneurysm ZHANG Xingyu, LI Ruogu 2025, 45 (6):  735-744.  doi: 10.3969/j.issn.1674-8115.2025.06.008 Abstract ( 452 )   HTML ( 16 )   PDF (4469KB) ( 2077 )   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. Figures and Tables | References | Related Articles | Metrics

Clinical research

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Pharmacokinetics/pharmacodynamics of antibiotics with different protein binding rates in hemodialysis SHEN Yue, WANG Yu, XU Jingyi, CHEN Yuancheng, ZHANG Jing, DING Feng 2025, 45 (6):  745-752.  doi: 10.3969/j.issn.1674-8115.2025.06.009 Abstract ( 400 )   HTML ( 5 )   PDF (1909KB) ( 1489 )   Objective ·To evaluate the clearance and pharmacokinetics/pharmacodynamics (PK/PD) of antibiotics from the perspective of protein binding rates in critically ill patients undergoing intermittent hemodialysis (IHD), in order to explore the association between protein binding rate and dialysis clearance of antibiotics, and to provide theoretical basis for developing antibiotic dosing regimens during hemodialysis. Methods ·Nineteen patients undergone low-flux hemodialysis and received antibiotic therapy at the Department of Nephrology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, were enrolled and divided into the meropenem group (n=7), the vancomycin group (n=5) and the ceftriaxone group (n=7) according to the type of antibiotics. A liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was established to detect meropenem, vancomycin, and ceftriaxone in human plasma/serum and dialysate. A two-compartment pharmacokinetic model was established using MATLAB. Instantaneous and total dialysis clearance rates were calculated, and PK/PD parameters were analyzed. Results ·No significant differences were found in the clinical characteristics of subjects among the three groups. The dialysis clearance rates were as follows: meropenem group (5.14‒5.97 L/h) > vancomycin group (2.87‒3.77 L/h)> ceftriaxone group (1.21‒1.90 L/h), with statistically significant differences (P<0.001). All three antibiotics showed good fit in the two-compartment pharmacokinetic model with a dialysate chamber (fval%<2), and the calculated PK/PD parameters were consistent with previous literature. For meropenem, the fraction of time that the free drug concentration remained above the minimal inhibitory concentration (%fT>MIC) values were 95.2%, 60.8% and 32.4% at minimal inhibitory concentration (MIC) values of 2, 8 and 16 μg/mL, respectively. For ceftriaxone (free concentration), the %fT>MIC values were all above 45.0% at MICs of 0.25, 4 and 16 μg/mL. For vancomycin, only 14.0% of the trough concentrations reached the target range of 15‒20 mg/L. Conclusion ·The three antibiotics are well described by the two-compartment model. The plasma protein binding rate has a significant effect on the dialysis clearance of antibiotics in low-flux IHD, with higher protein binding associated with lower clearance. The regimens of meropenem (0.5 g/d) and ceftriaxone (2.0 g/d) are generally effective among patients undergoing low-flux IHD, while the vancomycin regimen with a loading dose of 1.0 g and a maintenance dose of 0.5 g/2 d carries a risk of treatment failure. Figures and Tables | References | Related Articles | Metrics

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Postoperative neurodevelopmental outcomes of end-to-side anastomosis for coarctation of the aorta LI Zhuohang, YU Xindi, REN Jingya, SHEN Jia, DONG Suzhen, WANG Wei 2025, 45 (6):  753-759.  doi: 10.3969/j.issn.1674-8115.2025.06.010 Abstract ( 240 )   HTML ( 4 )   PDF (1369KB) ( 496 )   Objective ·To analyze the neurodevelopmental outcomes of children after end-to-side anastomosis for coarctation of the aorta (CoA). Methods ·The surgical and neurological follow-up data were collected from children who underwent end-to-side anastomosis for CoA at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine from January 1, 2017 to December 31, 2021. Neurological assessments included magnetic resonance imaging (MRI) and Griffiths Mental Development Scale assessments. Neurodevelopmental outcomes were evaluated using Griffiths Mental Development Scale. Clinical characteristics were compared between patients with normal and abnormal MRI and Griffiths Mental Development Scale results to assess the correlation between the two assessments and their association with cardiopulmonary bypass (CPB) use and CPB modality. Results ·Twenty-seven children with isolated CoA or CoA combined with simple intracardiac anomalies were included. MRI results were available for 25 cases, with 5 showing abnormalities (20.0%). Griffiths Mental Development Scale results were available for 26 cases, with 21 (80.77%) showing abnormal scores, including 18 in hearing and language, and 12 in performance. No significant correlation was found between abnormal MRI or Griffiths Mental Development Scale results and the use of CPB (P=0.341, P=1.000). Among patients who underwent CPB, those in the moderate hypothermia group accounted for the majority of cases without neurological abnormalities, with proportions of 80.00% (MRI) and 100.00% (Griffiths Mental Development Scale). Conclusion ·Children undergone end-to-side anastomosis for CoA are at relatively high risk for neurodevelopmental abnormalities, particularly in hearing-language and performance domains. CPB may not be a direct risk factor for poor neurodevelopmental outcome, and moderate hypothermia during CPB may be neuroprotective. Figures and Tables | References | Related Articles | Metrics

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Correlation between brain imaging features and cognitive impairment in end-stage renal disease patients based on susceptibility-weighted imaging GU Liangrui, YAN Bicong, FANG Tonglei, WU Jinliang 2025, 45 (6):  760-765.  doi: 10.3969/j.issn.1674-8115.2025.06.011 Abstract ( 233 )   HTML ( 8 )   PDF (2179KB) ( 618 )   Objective ·To assess the number and distribution of cerebral microbleeds (CMBs) in patients with end-stage renal disease (ESRD) using susceptibility-weighted imaging (SWI), and to explore the relationship between SWI-detected imaging features and cognitive impairment. Methods ·Hospitalized ESRD patients who had received dialysis treatment for more than one year at Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, between January 2023 and March 2024 were included. All patients underwent conventional MRI sequences and SWI scanning. The number and regional distribution of CMBs were recorded. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Patients with MoCA scores ≥26 were classified into the ESRD without cognitive impairment group, and those with scores <26 were placed in the ESRD with cognitive impairment group. The presence and number of CMBs were analyzed in relation to cognitive impairment. The distribution of CMBs in various brain regions was examined, and correlations between the number of CMBs in specific regions and the severity of cognitive impairment were evaluated. Results ·A total of 38 patients were enrolled, including 16 in the ESRD with cognitive impairment group and 22 in the non-impaired group. CMBs were more frequently observed in the cognitively impaired group (14 cases, 87.50%) compared to the non-impaired group (12 cases, 54.55%), with a statistically significant difference (P=0.033). The impaired group had more CMBs (106 in total), primarily located in bilateral cortical and subcortical regions (59.43%) and the basal ganglia (19.81%). In contrast, the non-impaired group had fewer CMBs (47 in total), mainly located in the bilateral basal ganglia (46.80%) and cortical and subcortical regions (40.43%), with all regional distribution differences being statistically significant (both P<0.05). Among those with cognitive impairment, the number of CMBs in the cortical and subcortical areas was significantly negatively correlated with cognitive function (r=-0.718, P=0.030). Conclusion ·The number and distribution of CMBs detected by SWI in ESRD patients are associated with both the presence and severity of cognitive impairment. SWI can be used to identify CMBs formation and localization in ESRD patients, thereby aiding in the assessment of cognitive dysfunction. Figures and Tables | References | Related Articles | Metrics

Evidence-based medicine

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Mendelian randomization analysis of causal relationship between celiac disease and autoimmune thyroid disease YAN Junhao, GUO Xiaolei, LUO Zhaofeng, TANG Jian, WANG Zheng 2025, 45 (6):  766-773.  doi: 10.3969/j.issn.1674-8115.2025.06.012 Abstract ( 277 )   HTML ( 4 )   PDF (2059KB) ( 700 )   Objective ·To investigate the bidirectional causal relationships between celiac disease (CeD) and Hashimoto thyroiditis (HT) as well as Graves disease (GD), using a two-sample Mendelian randomization (MR) approach. Methods ·Single nucleotide polymorphisms (SNPs) related to CeD, HT and GD were extracted from publicly available Genome-Wide Association Studies (GWAS) databases and used as instrumental variables. The inverse-variance weighted (IVW) method served as the primary analytical approach, supplemented by MR-Egger, weighted median (WME) and weighted mode (WMO) methods, to evaluate the causal associations between CeD and both HT and GD. Replication analyses using alternative GWAS datasets were conducted to validate the robustness of the results. Heterogeneity was assessed using Cochran's Q test, and pleiotropy was evaluated via MR-Egger intercept test. Leave-one-out analyses were performed to assess the impact of individual SNPs on the results. Results ·The IVW analysis results indicated that genetically predicted CeD significantly increased the risk of HT [discovery group: OR=1.186 (95%CI 1.114‒1.262), P<0.001; replication group: OR=1.218 (95%CI 1.090‒1.361), P<0.001] and GD [discovery group: OR=1.214 (95%CI 1.155‒1.276), P<0.001; replication group: OR=1.273 (95%CI 1.161‒1.396), P<0.001]. However, reverse MR analyses did not provide evidence for a causal relationship between HT and CeD, while genetically predicted GD significantly increased the risk of CeD [discovery group: OR=1.259 (95%CI 1.006‒1.576), P=0.044; replication group: OR=1.387 (95%CI 1.233‒1.560), P<0.001]. Sensitivity analyses suggested that the results were not influenced by horizontal pleiotropy. Conclusion ·CeD may be causally associated with a higher risk of HT and GD, while GD may increase the risk of developing CeD. HT does not appear to have an impact on CeD. Figures and Tables | References | Related Articles | Metrics

Techniques and methods

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Rapid detection and typing of Staphylococcus aureus based on nanopore Cas9-targeted sequencing PAN Shufan, YANG Donglei, WANG Pengfei 2025, 45 (6):  774-783.  doi: 10.3969/j.issn.1674-8115.2025.06.013 Abstract ( 335 )   HTML ( 10 )   PDF (3280KB) ( 1025 )   Objective ·To achieve the rapid detection of Staphylococcus aureus using nanopore Cas9-targeted sequencing (nCATS) technology, and simultaneously perform staphylococcal protein A (spa) typing and staphylococcal cassette chromosome mec (SCCmec) typing. Methods ·The spa gene and SCCmec gene elements were selected as two regions of interest (ROIs) for targeted sequencing. Four types of CRISPR RNAs (crRNAs) were designed to form Cas9 ribonucleoproteins (RNPs) to cleave sequences flanking the two ROIs. For each crRNA, a 42 bp synthetic target DNA was designed. Appropriate crRNAs were screened, the cleavage system was optimized, and both the cleavage reaction time and Cas9 RNP synthesis temperature were determined based on the results of Cas9 RNP cleavage efficiency testing. Genomic DNA was extracted from a methicillin-resistant Staphylococcus aureus (MRSA) strain, and the ends flanking the cleaved ROIs were dephosphorylated and dA-tailed. Sequencing adapters were ligated, and sequencing was performed using a nanopore platform. The quality scores of the sequencing data were analyzed, and the obtained nucleic acid sequences were compared with those in the mecA, spa and SCCmec databases. Based on the comparison results, the presence of Staphylococcus aureus, MRSA or not, and spa and SCCmec types were determined. Results ·Two sets of crRNAs were designed. Based on grayscale analysis of electrophoresis results, the set with higher cleavage efficiency was selected for further experiments. Optimization showed that a 1∶1 ratio of Cas9 RNP to target DNA, a 15 min cleavage reaction time, and a Cas9 RNP synthesis temperature of 25 ℃ yielded a cleavage efficiency of 87.41%. nCATS sequencing quality scores ranged between 15 (Q15) and 20 (Q20), indicating an approximate sequencing accuracy of 99%. Sequence comparisons with the mecA, spa and SCCmec databases revealed that the strain's spa type was t2 and its SCCmec type was Ⅱ. These results were consistent with those obtained by PCR amplification sequencing and multiplex PCR. Conclusion ·The nCATS technique enables rapid detection of Staphylococcus aureus, while simultaneously providing spa and SCCmec typing information. Figures and Tables | References | Related Articles | Metrics

Review

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Pathogenic mechanisms and therapeutic advances of small colony variants LIANG Xiaoning, SHI Tingwang, CHEN Yunfeng 2025, 45 (6):  784-791.  doi: 10.3969/j.issn.1674-8115.2025.06.014 Abstract ( 415 )   HTML ( 17 )   PDF (1391KB) ( 2381 )   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. Figures and Tables | References | Related Articles | Metrics

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Research progress on macrophage metabolic regulation in wound healing of diabetes mellitus type 2 HUANG Yinghe, ZHAO Guanyu, SUN Yang, HOU Jianji, ZUO Yong 2025, 45 (6):  792-799.  doi: 10.3969/j.issn.1674-8115.2025.06.015 Abstract ( 406 )   HTML ( 8 )   PDF (1990KB) ( 2273 )   The global prevalence of diabetes among adults is increasing year by year, with diabetes mellitus type 2 (T2DM) being the most common form. T2DM is a chronic disease characterized by insulin resistance and insufficient insulin secretion, often accompanied by disturbances in glucose, protein, and lipid metabolism. Impaired wound healing is one of the major complications of T2DM. Studies have shown that wound healing in T2DM patients are regulated by macrophages and are closely related to their phenotype, activity, and abundance. Macrophages of different phenotypes play distinct roles in various stages of T2DM wound healing: M1 macrophages are involved in the early inflammatory response and pathogen clearance, while M2 macrophages contribute to anti-inflammatory responses and wound repair during later stages. Dysregulation of macrophage phenotype switching affects wound inflammatory response, skin cell function, and extracellular matrix (ECM) synthesis, ultimately leading to impaired healing. Significant progress has been made in understanding the interactions between macrophage metabolic changes and phenotype switching, and this dynamic relationship might play a synergistic role in regulating the wound healing process in T2DM. This review summarizes the functional roles of macrophages in both normal and T2DM-associated wound healing, discusses alterations in glucose, lipid, and amino acid metabolism in macrophages under pathological conditions, and explores how these metabolic shifts regulate wound healing. Furthermore, it examines the therapeutic potential of targeting macrophage metabolism to improve wound healing outcomes. Figures and Tables | References | Related Articles | Metrics

Brief original article

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Multi-omics analysis of methylmalonic acidemia caused by a non-coding region variant in MMAA gene combined with uniparental disomy HUO Xiaoyan, LUO Xiaomei, YE Xiantao, SUN Yu, YU Yongguo, LIANG Lili, FAN Yanjie 2025, 45 (6):  800-806.  doi: 10.3969/j.issn.1674-8115.2025.06.016 Abstract ( 293 )   HTML ( 3 )   PDF (2214KB) ( 637 )   Objective ·To investigate the genetic etiology of a rare and complex case clinically suspected to be methylmalonic acidemia (MMA), but with negative whole exome sequencing (WES) results, using a multi-omics sequencing approach. Methods ·DNA and RNA samples were extracted from the peripheral blood of the proband and both parents. Targeted MMA-related gene Panel sequencing and WES were first performed. Subsequently, RNA sequencing (RNA-seq) and whole genome sequencing (WGS) were conducted to comprehensively analyze the child's genetic variants, their origins and potential inheritance patterns. Results ·No pathogenic variants associated with the patient's phenotype were identified through the MMA Panel or standard WES analysis. Extended analysis of WES suggested the possibility of uniparental disomy (UPD) of chromosome 4. WGS revealed a homozygous splice-site variant (c.-66+2T>C) in the non-coding region of the metabolism of cobalamin associated A (MMAA) gene. The variant was located in the 5' untranslated region (5'UTR), specifically at the second base downstream of the splice donor site of exon 1 (reference sequence: NM_172250). In genomic coordinates (hg19), the variant was located at base 146540561 on chromosome 4 (chr4:146540561). Sanger sequencing confirmed that the mother was heterozygous for this variant, while the father did not carry it. RNA-seq showed no detectable expression of the MMAA gene on chromosome 4 in the patient. This was further confirmed by reverse transcription real time quantitative PCR, indicating nearly absent mRNA expression, suggesting that the non-coding splice-site variant affected transcriptional expression. Conclusion ·A homozygous splice-site variant (c.-66+2T>C) in the non-coding region of the MMAA gene—outside the coverage of WES—is likely the pathogenic cause in this case, presumably resulting from maternal UPD of chromosome 4. Figures and Tables | References | Related Articles | Metrics