Since 2020, the international community has successively proposed new nomenclatures for metabolic dysfunction-associated fatty liver disease (MAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD). In 2024, the Chinese Society of Hepatology updated and published the Guideline for the prevention and treatment of metabolic dysfunction-associated (non-alcoholic) fatty liver disease (version 2024). This review deeply analyzes the differences between MASLD and MAFLD in terms of concept, definition framework, and clinical management. On this basis, it provides an in-depth interpretation of the updated highlights and features of the working definition in the 2024 updated Chinese guideline.
ObjectiveTo investigate the correlation between different forms of serum vitamin D levels and liver fibrosis in patients with metabolic dysfunction-associated fatty liver disease (MAFLD).MethodsData from the National Health and Nutrition Examination Survey in 2021–2023 were analyzed. Logistic regression models were used to evaluate the relationship between serum total vitamin D, 25(OH)D3 levels, and liver fibrosis in the MAFLD patients.ResultsA total of 2 628 patients were included. There were significant differences between MAFLD patients with liver fibrosis and those without fibrosis in age, smoking history, waist circumference, body mass index, high-density lipoprotein cholesterol, total cholesterol, fasting plasma glucose, hypertension history, vitamin D, and 25(OH)D3 levels (P<0.05). Logistic regression analysis revealed that compared to the low total serum vitamin D group (11.2-61.8 nmol/L), MAFLD patients with high total vitamin D levels (89.1 nmol/L<vitamin D≤290 nmol/L) exhibited a 22% reduced risk of liver fibrosis (OR=0.78, 95%CI 0.64-0.94, P=0.015). Similarly, compared to the low 25(OH)D3 group (4.1-57.0 nmol/L), those with high 25(OH)D3 level [84.7 nmol/L<25(OH)D3≤288 nmol/L] showed a 23% lower risk of liver fibrosis (OR=0.77, 95%CI 0.62-0.95, P=0.021). After adjusting for covariates, high total vitamin D levels remained significantly associated with reduced liver fibrosis risk (OR=0.63, 95%CI 0.42-0.94, P=0.036).ConclusionsElevated serum total vitamin D and 25(OH)D3 levels are protective factors against early liver fibrosis in MAFLD patients.
ObjectiveTo investigate expression changes and regulatory roles of adhesion G protein-coupled receptor F1 (ADGRF1/GPR110) in metabolic dysfunction-associated steatohepatitis (MASH)-related hepatic fibrosis.MethodsHuman MASH liver tissues were collected for GPR110 detection via real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. Eight-week-old male C57BL/6 mice were randomly divided into four groups: control+AAV-GFP group, control+AAV-GPR110 group, MASH+AAV-GFP group, and MASH+AAV-GPR110 group. MASH was induced by high-fat with high-sucrose diet and low-dose CCl4 intraperitoneal injections, with AAV-GPR110/AAV-GFP delivered via tail vein. Liver tissues were harvested at designated intervals (4 w, 8 w, and 12 w). Western blotting measured GPR110 expression; hematoxylin-eosin and oil red O staining assessed histology and lipid content; F4/80 and -smooth muscle actin (-SMA) immunofluorescence staining evaluated inflammation and fibrosis; qRT-PCR quantified hepatic expression of lipid metabolism, inflammatory, and fibrotic genes.ResultsGPR110 expression was significantly reduced in livers of MASH patients compared with controls (P<0.05). MASH+AAV-GPR110 mice exhibited lower weight, liver index, and serum lipids compared with MASH+AAV-GFP (P<0.05). Lipid synthesis-related gene (SCD-1), lipid uptake-related gene (CD36), gluconeogenesis-related genes (PEPCK and G-6-Pase), and inflammation-related genes (TNF-, NF-B, and iNOS) in liver were downregulated in MASH+AAV-GPR110 (P<0.05). Hepatic F4/80+ and -SMA+ areas decreased in MASH+AAV-GPR110 (P<0.05).ConclusionGPR110 overexpression ameliorates hepatic lipid accumulation, reduces inflammation, and delays fibrosis in MASH.
ObjectiveTo explore the efficacy and safety of dapagliflozin in patients with paroxysmal atrial fibrillation (PAF) combined with heart failure with preserved ejection fraction (HFpEF).MethodsA total of 120 patients with PAF combined with HFpEF treated at Jinshan Hospital of Fudan University from July 2022 to July 2023 were selected and randomly divided into the dapagliflozin group (n=60, standard treatment combined with dapagliflozin) and the control group (n=60, standard treatment combined with placebo). After 12 months of follow-up, the Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS), PAF duration, recurrence rate and frequency of PAF, left atrial diameter, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, left ventricular ejection fraction, P-wave dispersion, blood pressure, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP), estimated glomerular filtration rate (eGFR), and glycated hemoglobin A1C (HbA1C) were compared between the two groups. Cardiovascular outcomes and adverse events were observed.ResultsA total of 10 patients lost to follow-up, and 110 patients were included in the analysis (55 in each group). After 12 months of treatment, the KCCQ-TSS in the dapagliflozin group was significantly higher than that in the control group ([61.68±2.65] points vs [44.98±4.76] points, P<0.001). The PAF duration in the dapagliflozin group was significantly shorter than that in the control group ([144±18] min vs [270±24] min, P=0.045). After treatment, frequency of PAF, NT-proBNP levels, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, left atrial diameter, P-wave dispersion, and HbA1C levels showed statistical differences between the two groups (P<0.05). The heart failure readmission rate and PAF recurrence rate in the dapagliflozin group were significantly lower than those in the control group (P<0.05). There was no significant difference in the incidence of adverse events between the two groups during treatment.ConclusionsDapagliflozin improves patients' quality of life, reduces PAF duration and recurrence rate, decreases heart failure readmission rate, lowers NT-proBNP levels, reverses cardiac remodeling, and demonstrates favorable safety in patients with PAF combined with HFpEF.
ObjectiveTo explore the application of plasma 7 microRNA (miR7) testing in the differential diagnosis of very early-stage hepatocellular carcinoma (HCC).MethodsThis study is a multicenter real-world study. Patients with single hepatic lesion (maximum diameter≤2 cm) who underwent plasma miR7 testing at Zhongshan Hospital, Fudan University, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Anhui Provincial Hospital, and Peking University People's Hospital between January 2019 and December 2024 were retrospectively enrolled. Patients were divided into very early-stage HCC group and non-HCC group, and the clinical pathological characteristics of the two groups were compared. The value of plasma miR7 levels, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) in the differential diagnosis of very early-stage HCC was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). In patients with both negative AFP and DCP (AFP<20 ng/mL, DCP<40 mAU/mL), the diagnostic value of plasma miR7 for very early-stage HCC was analyzed.ResultsA total of 64 528 patients from 4 hospitals underwent miR7 testing, and 1 682 were finally included, of which 1 073 were diagnosed with very early-stage HCC and 609 were diagnosed with non-HCC. The positive rate of miR7 in HCC patients was significantly higher than that in non-HCC patients (67.9% vs 24.3%, P<0.001). ROC curves showed that the AUCs for miR7, AFP, and DCP in distinguishing HCC patients from the non-HCC individuals were 0.718, 0.682, and 0.642, respectively. The sensitivities were 67.85%, 43.71%, and 44.45%, and the specificities were 75.70%, 92.78%, and 83.91%, respectively. The pairwise comparison of AUCs showed that the diagnostic efficacy of plasma miR7 detection was significantly better than that of AFP or DCP (P<0.05). Although its specificity was slightly lower than AFP and DCP, the sensitivity was significantly higher. Among patients negative for both AFP and DCP, miR7 maintained an AUC of 0.728 for diagnosing very early-stage HCC, with 67.82% sensitivity and 77.73% specificity.ConclusionsPlasma miR7 testing is a potential molecular marker with high sensitivity and specificity for the differential diagnosis of small hepatic nodules. In patients with very early-stage HCC lacking effective molecular markers (negative for both AFP and DCP), miR7 can serve as a novel and effective molecular marker to assist diagnosis.
ObjectiveTo evaluate the safety and efficacy of simultaneous resection for initially resectable rectal cancer with synchronous liver metastases.MethodsA retrospective analysis was conducted on 305 patients with initially resectable rectal cancer with synchronous liver metastases. These patients were diagnosed at Zhongshan Hospital, Fudan University from January 2016 to June 2020. Among them, 191 underwent simultaneous rectum and liver resection and 114 underwent staged resection. Propensity score matching (PSM) was performed at a 1∶1 ratio. Clinical data were compared and Kaplan-Meier survival curves were plotted.ResultsAfter PSM, 85 patients were included in each group. General data showed no significant differences. Except for liver metastasis resection method, no statistical differences were found in primary tumor surgery approach, intraoperative blood loss, intraoperative complications, time to first flatus and defecation, 30-day mortality, and postoperative hospital stay between the simultaneous resection group and the staged resection group. The overall complication rate was higher in the simultaneous resection group (48.2% vs 29.4%, P=0.04). Specifically, the grade Ⅱ complications were significantly higher (29.4% vs 14.1%, P=0.016), but there's no differences in severe complications (grade Ⅲ-Ⅴ). No statistically differences were observed in median progressionfree survival (HR=0.70, 95%CI 0.50-0.97, P=0.103) and 5-year overall survival (HR=0.95, 95%CI 0.63-1.44, P=0.259).ConclusionsSimultaneous resection demonstrates comparable safety and efficacy to staged resection for initially resectable rectal cancer with synchronous liver metastases.
ObjectiveTo explore the feasibility, safety, and efficacy of transesophageal endoscopic surgery for mediastinal tumors.MethodsA retrospective analysis was conducted on the clinical data of 17 patients who underwent transesophageal endoscopic resection for benign mediastinal tumors at the Endoscopy Center of Zhongshan Hospital, Fudan University, between January 1, 2016 and December 31, 2024. Epidemiological characteristics, surgical parameters, adverse events, and follow-up outcomes were analyzed.ResultsAmong the 17 patients, there were 9 males and 8 females, with an average age of (42.4±14.5) years and an average tumor size of (2.6±1.6) cm. Pathological types included esophageal duplication cysts (6 cases, 35.3%), bronchogenic cysts (5 cases, 29.4%), gastroenteric cysts (3 cases, 17.6%), schwannomas (2 cases, 11.8%), and lymphangioma (1 case, 5.9%). Fourteen patients (82.4%) underwent submucosal tunneling endoscopic resection (STER), 3 patients (17.6%) underwent natural orifice transluminal endoscopic mediastinal surgery. All surgeries were successfully completed without conversion to open surgery. En bloc resection was achieved in 11 patients (64.7%), with an average operative time of (60.9±32.6) min. No intraoperative bleeding or mucosal injury occurred, and 4 patients (23.5%) experienced minor complications (pneumothorax, fever, recurrent laryngeal nerve injury), all of which resolved with conservative treatment. The average postoperative hospital stay was (3.2±1.5) days, and no recurrence was observed during the follow-up period.ConclusionsTransesophageal endoscopic resection of benign mediastinal tumors is a safe, effective, and minimally invasive treatment method. Further validation of its efficacy and safety through large-scale prospective studies is warranted.
ObjectiveTo explore the diagnostic value of endoscopic grading of gastric intestinal metaplasia (EGGIM) score under acetic acid-enhanced narrow band imaging (AA-NBI) observation mode for gastric intestinal metaplasia (GIM).MethodsA total of 120 patients who underwent gastroscopy at Jinshan Hospital of Fudan University from February 2022 to February 2023 were selected. All patients underwent both white light and AA-NBI endoscopy, with photographic records of intestinal metaplasia in five areas: greater curvature of antrum, lesser curvature of antrum, greater curvature of corpus, lesser curvature of corpus and incisura. EGGIM score was performed: 0 for no intestinal metaplasia, 1 point for focal intestinal metaplasia (GIM area ratio≤30%), 2 points for extensive intestinal metaplasia (GIM area ratio>30%), with a total score of 10 points. Targeted biopsies were performed on suspicious GIM lesions found during endoscopy. If no suspicious GIM lesions were observed, random biopsies were performed according to the updated Sydney system. The pathological histological examination results were staged based on the operative link on gastric intestinal metaplasia assessment (OLGIM) system. The diagnostic value of EGGIM score for OLGIM stage Ⅲ-Ⅳ patients was evaluated using receiver operating characteristic (ROC) curves.ResultsThe sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of AA-NBI in detecting GIM were 96.3%, 91.6%, 94.5%, 95.0%, and 93.6%, respectively. The area under the ROC curve for EGGIM diagnosing OLGIM stage Ⅲ-Ⅳwas 0.952 (95%CI 0.914-0.990). The optimal cut-off value for EGGIM was 5 points, with a sensitivity of 96.7% (95%CI 87.6%-99.4%) and specificity of 88.1% (95%CI 76.5%-94.7%).ConclusionsEGGIM score (≥5 points) under AA-NBI mode has good diagnostic capability for patients with OLGIM stage Ⅲ-Ⅳ.
ObjectiveTo evaluate the image quality of abdominal dual-energy CT virtual monoenergetic imaging (VMI) in patients with early gastric cancer using titanium alloy clips and assess its effectiveness on reducing metal artifacts.MethodsA retrospective study was conducted, including 31 patients with gastric cancer who underwent abdominal dual-energy CT scans with titanium clips inserted in the gastric cavity. Each scan was reconstructed into mixed images (simulated 120 kVp CT) and VMIs with energy levels ranging from 40 keV to 140 keV. Metal artifacts were quantitatively evaluated by measuring the noise values in the lesion and perigastric regions. The contrast-noise ratio (CNR) of the lesion and the corresponding liver tissue was calculated to assess the image quality. Two radiologists independently evaluated the images, considering overall quality, artifact severity, lesion conspicuity, perigastric clarity, and vascular contrast.ResultsQuantitative analysis revealed that metal artifacts in both the lesion and perigastric regions decreased as the energy level increased. VMIs at 80-140 keV (lesion site) and 90-140 keV (perigastric space) showed significantly fewer artifacts compared to mixed images (P<0.05). The CNR of lesions remained stable across VMIs at 50-140 keV, while the CNR of normal liver tissue decreased significantly with increasing energy (P<0.05). In the subjective assessment, VMIs at 80-140 keV had higher artifact scores than mixed images (P<0.05). VMIs at 70-90 keV provided better lesion conspicuity and perigastric clarity, although vascular contrast decreased significantly with increasing energy (P<0.05). VMIs at 70-90 keV showed better overall quality (P<0.05), though not significantly different from mixed images.ConclusionsVMIs at 80 keV and 90 keV improve the visibility of lesions and perigastric regions affected by metallic clips, which combined with mixed images can enhance radiologists' diagnostic accuracy.
ObjectiveTo explore the role and related mechanism of neutrophil membrane-coated poly (lactic-co-glycolic acid) (PLGA) nanoparticles (Neu-NP) in cardiac repair after acute myocardial ischemia-reperfusion (MI/R) injury in mice.MethodsThe male C57 mouse model of acute MI/R injury was established and randomly divided into three groups: PBS control group (injection of 200 L PBS), NP treatment group (injection of 0.5 mg/mL NP 200 L), and Neu-NP treatment group (injection of 0.5 mg/mL Neu-NP 200 L). Neutrophil membranes were extracted and fused with PLGA nanoparticles to construct biomimetic Neu-NP. The in vivo homing ability of Neu-NP was assessed using ex vivo imaging technology in the MI/R injury model, and the expression levels of tumor necrosis factor- (TNF-) and interleukin-6 (IL-6) in the myocardium were measured using enzyme linked immunosorbent assay one day and three days after administration. Echocardiography was used to determine cardiac function indicators of MI/R injured mice 28 days post-administration. Immunofluorescence staining was used to observe angiogenesis repair and inflammatory cell infiltration in mouse heart tissue.ResultsNeu-NP, engineered by integrating neutrophil membranes with nanoparticles, inherited surface receptors (TNF-R and IL-6R) and functioned as decoys for inflammatory targeting. Compared with the PBS control group and NP treatment group, the secretion levels of TNF- and IL-6 in the damaged myocardium of the Neu-NP treatment group were significantly decreased one and three days after administration (P<0.05); 28 days after administration, the cardiac ejection fraction in the Neu-NP treatment group was significantly higher than that in the other two groups (P<0.05). Immunofluorescence staining indicated a significant increase in the proportion of angiogenesis in the myocardial infarction area and a significant reduction in inflammation cell infiltration (P<0.05).ConclusionsNeu-NP plays an important role in cardiac tissue repair after MI/R injury by alleviating inflammatory factors in the damaged area and promoting angiogenesis.
ObjectiveTo investigate dynamic changes in myocardial protein phosphorylation during the acute phase of myocardial infarction (MI) in mice.MethodsSix 8-week-old C57BL/6J mice were randomly assigned to MI model (n=3) or sham-operated control (n=3) groups. Cardiac tissues were harvested 72 hours post-intervention for proteomic analysis. Phosphorylation modifications were systematically characterized using liquid chromatography-mass spectrometry (LC-MS). Bioinformatics analyses included differential phosphorylation screening, functional enrichment, hierarchical clustering, and protein-protein interaction network.ResultsLC-MS identified 1 921 differentially phosphorylated sites (20 tyrosine and 1 901 serine/threonine sites) across 851 proteins. Compared with controls, MI hearts exhibited significant phosphorylation upregulation at 1 545 sites and downregulation at 376 sites (P<0.05).ConclusionsThis study delineates MI-associated phosphorylation dynamics, providing mechanistic insights and potential therapeutic targets for acute MI intervention.
ObjectiveTo explore the protective effect of exercise-induced metabolite-3 (EIM-3) on myocardial ischemia-reperfusion (I/R) injury and explore its underlying molecular mechanisms.MethodsThe physicochemical properties and half-life of EIM-3 were analyzed using the Human Metabolome Database (HMDB, https://hmdb.ca/). A primary rat cardiomyocyte hypoxia/reoxygenation (H/R) injury model was established. Cell apoptosis and viability were assessed using TUNEL assay and cell counting kit-8, respectively. Lactate dehydrogenase (LDH) levels in the cell culture supernatant were measured. Intracellular reactive oxygen species (ROS) levels were detected. Transcriptomic analysis was performed to identify potential signaling pathways and targets of EIM-3.ResultsPlasma levels of EIM-3 were elevated post-exercise. EIM-3 was characterized as a phospholipid small-molecule compound with a partition coefficient (logP) of 5.58 and a solubility (logS) of -7.6, indicating favorable lipophilicity and cell membrane permeability. In cardiomyocytes H/R injury modles, EIM-3 significantly inhibited apoptosis, increased cell viability, reduced intracellular ROS levels, and decreased LDH release (P<0.01). Transcriptomic analysis suggested that EIM-3 exerts its protective function potentially by regulating glucose metabolim. Quantitative real-time polymerase chain reaction results confirmed that EIM-3 significantly upregulated the transcriptional level of pyruvate kinase M2 (PKM2) in a dose-dependent manner (P<0.001).ConclusionsEIM-3 protects cardiomyocytes against I/R injury by modulating glucose metabolim. This study provides foundational insights into the mechanisms underlying exercise-induced cardioprotection.
ObjectiveTo explore the mechanism by which zinc-regulated transporters, iron-regulated transporter-likeprotein 4 (ZIP4) regulates glycolysis and its impact on tumor progression in cholangiocarcinoma (CCA), providing a theoretical basis for targeted therapy of CCA.MethodsZIP4 expression in CCA was analyzed using the GEPIA database. Immuno-histochemistry (IHC) was used to detect ZIP4 expression in 20 paired CCA and adjacent non-tumor tissues. Stable ZIP4-overexpressing CCA cell lines (ZIP4-OE) were established. Gene set enrichment analysis was used to screen differentially expressed genes and pathways in ZIP-OE CCA cells. ZIP4, N-myc proto-oncogene protein (MYCN), and histone-lysine N-methyltransferase 2E (KMT2E) were knocked down using small interfering RNAs (siRNAs). The expression of glycolysis-related gene (glucose transporter 1 [Glut1], hexokinase 2 [HK2], and lactate dehydrogenase A [LDHA]) was measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Glycolytic activity was assessed by measuring the extracellular acidification rate (ECAR). Cell proliferation was evaluated using colony formation assays, and cell migration was assessed using Transwell assays. A xenograft mouse model was constructed to examine CCA tumor growth. Protein levels of ZIP4, KMT2E, H3K4me3 (tri-methylation of lysine 4 on histone H3), and MYCN were detected by Western blotting.ResultsGEPIA database analysis and IHC results confirmed significantly higher ZIP4 expression levels in CCA tissues compared to adjacent non-tumor tissues (P<0.05). Compared to the control group, the ZIP4-OE group exhibited a significantly increased ECAR, along with significantly enhanced proliferation and migration abilities (P<0.01). Conversely, knockdown of ZIP4 suppressed CCA cells proliferation and migration. GEPIA analysis indicated that ZIP4 upregulates the transcription of oncogene MYCN, as well as glycolysis-related genes. Knockdown of MYCN abolished the ZIP4 overexpression-induced upregulation of Glut1, HK2, and LDHA gene transcription, reduced glycolysis, and significantly inhibited CCA cell proliferation and migration (P<0.05). Mechanistic studies demonstrated that ZIP4 increases H3K4me3 level via KMT2E, leading to MYCN transcription. Knockdown of KMT2E in CCA cells suppressed the ZIP4 overexpression-induced enhancement in H3K4me3 modification, resulting in MYCN downregulation and significantly reduced CCA cells proliferation and migration (P<0.05).ConclusionsZIP4 upregulates H3K4me3 modification through KMT2E, which recruits transcription factors to activate the transcription of MYCN. This subsequently enhances cellular glycolysis and promotes the proliferation and migration of CCA cells.
ObjectiveTo identify long non-coding RNA (lncRNA) associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and investigate their mechanisms.MethodsPeripheral blood samples were collected from RA-ILD patients (n=3), RA patients without lung involvement (n=3), and healthy controls (n=3). Next-generation sequencing was performed to screen differentially expressed lncRNA. A human fibrotic lung cell model was established by inducing the MRC-5 cell line with transforming growth factor- (TGF-). Following siRNA-mediated knockdown of target genes, changes in inflammatory and oxidative stress-related genes were analyzed via real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blotting and dual-luciferase reporter (DLR) assays were used to validate protein expression, ubiquitination levels, and nuclear translocation of oxidative stress regulators, and antioxidant response element (ARE) transcriptional activity. Rescue experiments were conducted to confirm the role of target lncRNA in oxidative stress and inflammation in fibrotic lung cells.ResultsHigh-throughput sequencing revealed significant downregulation of LINC00638 in RA-ILD patients. Knockdown of LINC00638 markedly reduced transcriptional levels of interleukin (IL)-4, nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and superoxide dismutase 2 (SOD2), while increasing IL-6, IL-1, interferon- (IFN-), and reactive oxygen species (ROS) levels. Furthermore, LINC00638 knockdown decreased Nrf2 protein expression, increased its ubiquitination, reduced nuclear translocation, and suppressed ARE transcriptional activity. In MRC-5 cells, LINC00638 knockdown combined with N-acetylcysteine treatment restored Nrf2 and HO-1 levels while reducing IL-6 expression.ConclusionsLINC00638 suppresses inflammatory responses in RA-ILD by activating the Nrf2/ARE antioxidant signaling pathway, suggesting its potential as a therapeutic target for diagnosis and treatment.
ObjectiveTo explore the expression of human epidermal growth factor receptor 2 (HER2) and its associations with clinical, pathological, and imaging characteristics in endometrial carcinoma (EC) patients.MethodsA retrospective analysis was conducted on 214 patients with newly diagnosed EC treated at Zhongshan Hospital, Fudan University, from January 2022 to December 2024. HER2 expression was assessed using immunohistochemistry (IHC) staining, and its associations with clinical characteristics, histopathological and imaging features were analyzed.ResultsThe HER2 expression rate (IHC score of 1+/2+/3+) in EC was 37.4% (80/214). HER2 expression was significantly associated with older age, advanced International Federation of Gynecology and Obstetrics (FIGO) stage, aggressive histological types, P53abn and low apparent diffusion coefficient (ADC) of preoperative pelvic magnetic resonance imaging (MRI). Multivariate analysis indicated that aggressive histological types (P=0.002) and low ADC of preoperative pelvic MRI (P=0.047) were independent factors associated with HER2 expression.ConclusionsADC of EC lesions may serve as a non-invasive predictive marker for HER2 expression, while histological type provides a critical basis for precisely guiding HER2 testing.
ObjectiveTo explore the influencing factors of coronary artery lesion severity in patients with acute coronary syndrome (ACS).MethodsClinical data of ACS patients admitted to Zhongshan Hospital, Fudan University from December 2017 to December 2019 were consecutively collected. The modified Gensini score was used to assess the severity of coronary artery lesions. Univariate and multivariate linear regression analyses were performed to identify independent factors associated with coronary artery lesion severity.ResultsA total of 1 689 ACS patients were included, with an average age of (64.04±11.45) years; 1 353 (80.11%) were male, and the mean modified Gensini score was (8.12±4.03). Multivariate linear regression analysis revealed that sex (=0.97, P=0.001), age (=0.03, P=0.021), estimated glomerular filtration rate (eGFR; =-0.03, P<0.001), low-density lipoprotein cholesterol (LDL-C; =0.58, P<0.001), apolipoprotein A1 (Apo A1; =-1.28, P=0.012), lipoprotein(a) [Lp(a); =0.001, P=0.033], and glycated hemoglobin A1C (HbA1C; =0.45, P<0.001) were independent influencing factors of the modified Gensini score.ConclusionsMetabolic indicators, including Apo A1, LDL-C, HbA1C, and Lp(a), may serve as risk factors for coronary artery lesion severity in ACS patients, with Apo A1 demonstrating the strongest impact.
ObjectiveTo explore predictive factors of severe community-acquired pneumonia (CAP) complicated with respiratory failure (RF) and to develop and internally validate a clinical prediction model.MethodsA retrospective study was conducted on 350 patients with severe CAP admitted to Tianyou Hospital Affiliated to Wuhan University of Science and Technology from September 2022 to December 2024. Patients were randomly divided into a training set (n=245) and a validation set (n=105) in a 7∶3 ratio, and further categorized into RF and non-RF groups. LASSO regression was applied to optimize variable selection. Multivariate logistic analysis was used to construct the prediction model, followed by internal validation.ResultsUnivariate regression analysis identified male, hypertension, diabetes, coronary heart disease, age, CURB-65 score, white blood cell count, neutrophil count, C-reactive protein (CRP), serum amyloid A, procalcitonin, and hospital stay as risk factors for RF in severe CAP, while albumin level was a protective factor. LASSO regression selected CURB-65 score, albumin level, and CRP for inclusion in the final model. The area under the receiver operating characteristic curve was 0.903 in the training set and 0.919 in the validation set. Calibration curve analysis demonstrated excellent agreement between predicted and observed probabilities in both sets, and Hosmer-Lemeshow goodness-of-fit tests indicated no significant deviations. Threshold probabilities ranged from 0.01 to 0.99 in both training and validation sets.ConclusionsCURB-65 score, albumin level, and CRP are independent predictors of RF in severe CAP. The clinical prediction model based on these factors exhibits strong discrimination, calibration, goodness-of-fit, and clinical utility.
ObjectiveTo explore the correlation between the triglyceride glucose-waist-to-height ratio (TyG-WHtR) and advanced cardiovascular-kidney-metabolic (CKM) syndrome.MethodsData from the National Health and Nutrition Examination Survey (NHANES) 2007–2018 were used and analyzed, including a total of 14 322 adult participants. The CKM syndrome is classified into 5 stages, with stages 0-2 categorized as the early phase and stages 3-4 as the advanced phase, which were subjected to dichotomous classification analysis. The TyG-WHtR was calculated using triglycerides, glucose, waist circumference, and height. Multivariate logistic regression was used to analyze the correlation between TyG-WHtR and advanced CKM syndrome, adjusting for variables such as age, sex, race, education level, poverty-income ratio (PIR), smoking status, and alcohol consumption. Restricted cubic spline (RCS) analysis was conducted to evaluate the nonlinear relationship between the TyG-WHtR and advanced CKM syndrome.ResultsAmong the 14 322 participants, advanced CKM syndrome accounted for 16.99%. The TyG-WHtR level in the advanced CKM syndrome group was significantly higher than that in the early CKM syndrome group (5.60±0.03 vs 5.02±0.02, P<0.001). Logistic regression showed that TyG-WHtR was an independent related factor for advanced CKM syndrome (OR=1.48, 95%CI 1.36-1.61, P<0.001). Subgroup analyses revealed that the TyG-WHtR was consistently associated with advanced CKM syndrome across different sex, rase, and age groups, with no significant interaction effects observed. RCS analysis revealed a nonlinear positive association between TyG-WHtR and advanced CKM syndrome (Poverall<0.001, Pnonlinear=0.014). When the TyG-WHtR exceeded 5, the risk of advanced-stage CKM syndrome showed a significant elevation.ConclusionsThe TyG-WHtR is an independent related factor for advanced CKM syndrome, with a particularly significant risk increase when TyG-WHtR exceeds 5.
ObjectiveTo explore the mediating effect of sleep quality between somatic symptoms and severity of depression in patients with depression.MethodsA total of 384 drug-naive patients diagnosed with depression were recruited from the Department of Psychological Medicine of Zhongshan Hospital, Fudan University, during the period from February to August 2024. The severity of depression, somatic symptoms, and sleep quality were assessed using Patient Health Qusetionaire (PHQ)-9, PHQ-15, and Pittsburgh sleep quality index (PSQI), respectively. Based on the PHQ-15 scores, all participants were stratified into two groups: a mild somatic symptoms group(<10 points, n=136)and a moderate-to-severe somatic symptoms group(≥10 points, n=248). Comparisons of sleep quality between the two groups were conducted, and partial correlation analysis was performed to examine the correlation between sleep quality and somatic symptoms. Additionally, linear regression and mediation analyses were conducted to investigate the mediating effect of sleep quality between somatic symptoms and severity of depression.ResultsThe PSQI scores in moderate-to-severe somatic symptoms group were significantly higher than those in mild somatic symptoms group (P<0.001). Partial correlation analysis indicated that, after controlling for depression severity, the positive correlation between PSQI and PHQ-15 scores remained significant in both groups (P<0.01). Regression analysis identified both sleep quality and somatic symptoms as predictors of severity of depression (P<0.001). Additionally, mediation analysis demonstrated that sleep quality partially mediated the relationship between somatic symptoms and severity of depression, accounting for 26.63% (0.090/0.338) of the total effect.ConclusionsIn patients with depression, sleep quality is associated with somatic symptoms, and both contribute to an increased risk of the severity of depression. Moreover, sleep quality plays a partial mediating effect between somatic symptoms and severity of depression, highlighting the importance of addressing sleep-related issues in the management of depression.
ObjectiveTo explore the clinical features of fulminant type 1 diabetes mellitus (FT1DM).MethodsThe clinical data of 6 patients with FT1DM who were hospitalized in Jinshan Hospital of Fudan University from April 2020 to August 2024 were retrospectively analyzed. Their data were compared with that of 30 patients diagnosed with non-fulminant type 1 diabetes mellitus (NFT1DM) and diabetic ketosis or diabetic ketoacidosis (DKA) who were admitted to the hospital during the same period. The clinical characteristics of FT1DM were summarized.ResultsAll 6 patients with FT1DM were male, with a disease course of 2.00 (1.75, 4.00) d. Three cases exhibited a history of prior infection, four tested positive for glutamic acid decarboxylase antibody (GADA), and five developed severe DKA. The glycated hemoglobin A1C (HbA1C) was (6.30±0.67)%, fasting C-peptide (FCP) was 0.07 (0.03, 0.15) ng/mL, 2-hour postprandial C-peptide (2h-CP) was 0.09 (0.03, 0.16) ng/mL. At discharge, all 6 patients received 4-injection insulin regimen, with a dose (0.69±0.15) U·kg-1·d-1. The body mass index (BMI), blood glucose/HbA1C, blood potassium/HbA1C, fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2h-PG), high-sensitivity C-reactive protein (hs-CRP), alanine aminotransferase (ALT), serum creatinine, and blood potassium levels in the FT1DM group were higher than those in the NFT1DM group (P<0.05), while HbA1C and glycated albumin (GA) levels were lower than NFT1DM group (P<0.05).ConclusionsFT1DM usually presents with an acute onset of DKA, may be accompanied by a history of preceding infection, and GADA can be positive. Patients with FT1DM have elevated blood glucose/HbA1C, blood potassium/HbA1C, FPG, 2h-PG, hs-CRP, ALT, serum creatinine, blood potassium levels, and require insulin therapy, while the HbA1C and GA levels are lower.
ObjectiveTo explore the utility of comprehensive geriatric assessment (CGA) in screening risk factors for osteosarcopenia (OS) among older adults (≥80 years old) and to evaluate the therapeutic efficacy of CGA-guided integrated interventions for OS.MethodsA total of 420 patients aged ≥80 years, recruited from the Department of Geriatrics, General Practice of The Affiliated Jiangyin Hospital of Nantong University, and community health centers from January 2022 to October 2024, were enrolled. Participants were classified into OS (n=139) and non-OS (n=281) groups based on diagnostic criteria. CGA was utilized to compare differences in general characteristics, laboratory indicators, comorbidities between groups. Binary logistic regression analysis identified independent risk and protective factors. Subsequently, 40 OS patients were randomly assigned to an intervention group (n=20) receiving integrated interventions including nutritional support, exercise training, and psychological management or a control group (n=20, receiving routine care). Appendicular skeletal muscle mass index (ASMI), grip strength, gait speed, and bone mineral density (BMD) T-score were compared between groups after 3 months.ResultsThe prevalence of OS in this cohort was 33.1%. Compared to the non-OS group, the OS group exhibited significant differences in age, body mass index (BMI), smoking history, comorbidity index, concomitant medication, cognitive impairment, visual and hearing impairment, sleep disorders, depression, marital status, social participation, activities of daily living, nutritional risk, total cholesterol, uric acid, and constipation (P<0.05). Logistic regression analysis identified age and comorbidity index as significant risk factors for OS, while BMI, married status, total cholesterol, and activities of daily living (assisted and independent) served as protective factors. The intervention group demonstrated significant improvements in grip strength, gait speed, BMD T-score, and male ASMI compared to controls (P<0.05).ConclusionsCGA demonstrates clinical utility in systematically identifying risk factors for OS in the old population. Multimodal interventions guided by CGA effectively improve musculoskeletal function in elderly OS patients.
ObjectiveTo explore the correlation between pre-pregnancy body mass index (BMI) and the risk of difficult airway during labor and delivery through grading changes of Mallampati test (MT).MethodsA total of 354 primiparous women who delivered at Obstetrics and Gynecology Hospital of Fudan University from October 2020 to April 2021 were enrolled and categorized into low BMI, normal BMI, and high BMI groups based on pre-pregnancy BMI. Changes in MT grading were analyzed during early labor, postpartum (20 minutes to 1 hour after placental delivery), and 48 hours postpartum. A multifactor logistic regression model was used to analyze the factors increased MT grading postpartum.ResultsAmong the 354 participants, 97 (27.4%) exhibited increased MT grading postpartum, with the proportion of women classified as MT grade 3-4 rising from 39 (11.0%) during early labor to 77 (21.8%) postpartum. By 48 hours postpartum, the number of women with MT grade 3-4 decreased to 21 (5.9%). Multifactor logistic regression analysis showed that low pre-pregnancy BMI (vs high BMI: OR=2.15, 95%CI 1.02-4.53, P=0.045) and snoring history during pregnancy (OR=2.32, 95% CI 1.38-3.90, P=0.001) were independent risk factors for postpartum MT grading elevation.ConclusionsMT grading might increase postpartum in parturients, with low pre-pregnancy BMI and prenatal snoring history identified as significant risk factors for elevated MT grading after delivery.
ObjectiveTo investigate the impact of anesthesia and surgery on hippocampal expression of Alzheimer's disease (AD)-associated proteins in 5×FAD transgenic mice and explore potential sex differences.Methods5×FAD mice were crossbred with C57BL/6J wild-type (WT) mice to generate offspring for genotypic confirmation. Four-month-old 5×FAD mice and littermate (LM) WT controls were allocated into 8 experimental groups (n=8/group): female/male 5×FAD control group, female/male 5×FAD anesthesia/surgery group, female/male LM control group, and female/male LM anesthesia/surgery group. Anesthesia/surgery groups underwent laparotomy under 1.4% isoflurane anesthesia, while control groups received no intervention. Hippocampal tissues were collected 24 hours post-procedure for Western blotting analysis of -catenin, glycogen synthase kinase 3 beta (GSK3), and phosphorylated GSK3 (p-GSK3) levels.ResultsFemale 5×FAD mice demonstrated significant reductions in -catenin levels and p-GSK3 expression compared to both sex-matched LM controls and male 5×FAD counterparts (P<0.05). No significant differences in these proteins were observed in male 5×FAD mice following anesthesia/surgery.ConclusionsThese findings reveal sex-specific responses to perioperative stress in AD, suggesting that anesthesia and surgery may affect female AD patients through hippocampal -catenin/GSK3 pathway modulation.
ObjectiveTo explore the value of high-frequency ultrasound in the detection of metastatic hepatocellular carcinoma and displaying lesion characteristics.MethodsA total of 38 paitients with hepatocellular carcinoma satellite lesions within 40 mm of subcutaneous tissue were underwent low-frequency (1-5 MHz) and high-frequency (6-9 MHz) ultrasound. Detection rates and ultrasonic features were compared.ResultsHigh-frequency grayscale ultrasound had a higher detection rate (71.1% vs. 36.8%, P<0.001). Subgroup analysis showed higher detection rates with chemotherapy history (88.9% vs. 33.3%, P=0.002), fatty liver (71.9% vs 31.3%, P<0.001) or superficial lesion (within 20 mm, 76.5% vs 41.2%, P=0.031). High-frequency ultrasound also showed clearer margins (P=0.004) and more arterial-phase rim enhancement (P=0.007).Conclusions6-9 MHz ultrasound detects metastatic hepatocellular carcinoma, especially superficial lesions, more effectively than 1-5 MHz ultrasound and better visualizes characteristics.
Epilepsy, which leads to an enduring high tendency to generate epileptic seizures, is a neurological disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to abnormal synchronous neuronal discharges. Patients with epilepsy are usually comorbid with various sleep disorders, such as restless leg syndrome/periodic limb movement disorder (RLS/PLMD), chronic insomnia and narcolepsy. Frequent seizures may increase the risk of suffering from sleep disorders; conversely, poor control of sleep disorders exacerbates epilepsy. This review discusses common types of sleep disorders in patients with epilepsy, reveals potential mechanisms, and introduces new advances in the treatment of comorbidity between epilepsy and sleep disorders. The aim is to provide an overview of the close interactions between epilepsy and sleep disorders, providing new ideas and experiences for more effective treatment of sleep disorders and improving the prognosis of patients with epilepsy.
Approximately 10% of the global adult population has diabetes, with accumulating evidence linking suboptimal vitamin D levels to an increased risk of type 2 diabetes and its complications. Current clinical studies suggest that vitamin D supplementation may enhance insulin sensitivity and improve glycemic control, prompting significant interest in its potential as a therapeutic intervention. However, further high-quality, large-scale randomized controlled trials are required to validate its efficacy in glucose metabolism regulation and clarify the underlying molecular mechanisms. These investigations will provide critical evidence to inform precision medicine approaches for diabetes prevention and management.
In February 2023, a 48-year-old male with cough and expectoration was admitted to the Department of Pulmonary and Critical Care Medicine of Peking University People's Hospital. CT indicated mediastinal soft-tissue mass under the tracheal carina. Meta-genomics next generation sequencing of mediastinal abscess suggested infection with Tropheryma whipplei, which was positive for periodic acid-Schiff staining. The patient had no history of diarrhea, weight loss, or joint pain. The patient was diagnosed with Whipple's disease and treated with ceftriaxone followed by trimethoprim-sulfamethoxazole therapy. After 1-year post-discharge therapy, the patieny's symptoms and general condition improved significantly, and remained to follow.
GBA1 gene mutation is an important genetic risk factor for Parkinson's disease (PD). This paper reports a case of a 43-year-old male PD patient carrying a rare heterozygous Thr408Met mutation in the GBA1 gene identified through whole-exome sequencing, leading to a diagnosis of GBA1-associated PD. The patient's motor symptoms were primarily characterized by bradykinesia and rigidity, without significant cognitive decline. Treatment with low-dose levodopa combined with a dopamine agonist resulted in significant symptomatic improvement.