南方医科大学学报杂志最新文献

Objectives: To analyze the expression pattern of Exoribonuclease Family Member 3 (ERI3) in hepatocellular carcinoma (HCC) tissues and its influences on long-term prognosis and cancer cell metastasis.

Methods: Based on the TCGA-LIHC dataset (including 377 HCC and 50 adjacent normal tissues), the differential expression of ERI3 was analyzed using DESeq2, and the results were validated using immunohistochemical data from the HPA database. A protein-protein interaction network was constructed using STRING and GeneMANIA. The prognostic value of ERI3 was assessed by Cox regression and Kaplan-Meier (KM) survival analyses, its diagnostic efficacy evaluated by ROC curve analysis, and its correlation with immune infiltration analyzed with ssGSEA algorithm. A nomogram prognostic model was established using multivariate Cox regression. For functional validation of ERI3 in vitro, a human HCC cell line SMMC-7721 with ERI3 knockdown was constructed, and the changes in cell proliferation, migration, and invasion were assessed using CCK-8, colony formation, wound healing, and Transwell assays.

Results: ERI3 was significantly overexpressed in HCC tissues (P<0.001) and its expression levels increased progressively with advanced TNM stages (T1-T4: P<0.001). In HCC patients, high ERI3 expressions were correlated with a reduced overall survival (HR=2.86, 95% CI: 1.68-4.88; P<0.001), disease-specific survival (HR=2.27, P=0.013), and progression-free interval (HR=1.83, P=0.012). Diagnostic efficacy analysis revealed an AUC of 0.955 (95% CI: 0.931-0.978) for ERI3. Immune infiltration studies demonstrated a positive correlation of ERI3 expression level with Th2 cells (r=0.340, P<0.001) and a negative correlation with Th17 cells (r=-0.284, P<0.001). Multivariate Cox regression analysis identified ERI3 as an independent prognostic factor for HCC (HR=1.987, P=0.003), and the constructed nomogram showed a good predictive accuracy (C-index=0.668). In SMMC-7721 cells, ERI3 knockdown significantly suppressed cell proliferation, migration, and invasion.

Conclusions: ERI3 overexpression promotes HCC cell proliferation, migration, and invasion and is strongly linked to a poor prognosis of the patients.

Objectives: To enhance the accuracy and reliability of 12-lead electrocardiogram (ECG) automatic diagnosis.

Methods: Herein we propose a 12-lead ECG automatic diagnosis model based on deep feature fusion (MRHL-ECGNet), which consists of a multi-scale feature extraction front-end, ResNet-34, a global feature mixing module, and a time-series analysis module. The Hyena Hierarchy Convolution Operator was applied to the 12-lead ECG automatic diagnosis task for more efficient capture of long-range dependencies while reducing computational complexity. Integrated Gradients (IG)-based interpretability analysis technology was used to achieve visualization of the decision-making basis of MRHL-ECGNet. The CPSC2018 dataset was used to train and test MRHL-ECGNet, and its performance was assessed using multiple quantitative evaluation indicators and evaluation experiments.

Results: In the 9-class ECG classification task on the test set, MRHL-ECGNet achieved an accuracy of 0.972, an AUC of 0.983, an F1 score of 0.864, a precision of 0.873, and a recall of 0.857, all surpassing other comparative models. This model only took 0.007 s to output a diagnosis for a single sample on a GPU and 0.156 s on a CPU, with a memory footprint of 67.196 MB.

Conclusions: The proposed MRHL-ECGNet model demonstrates excellent classification performance in 12-lead ECG automatic diagnosis with a lightweight design and good interpretability, and thus has great potential for clinical application in ECG-aided diagnosis.

Objectives: To explore the effects of sulforaphane (SFN) on Aβ42-activated U87 astrocyte-mediated apoptosis of SH-SY5Y neurons in vitro.

Methods: U87 cells treated with different concentrations of Aβ42, SFN or both were examined for changes in cell activity, IL-6 and TNF-α mRNA expression, release of IL-6 and TNF-α proteins, and expressions of p-p38, p-p65 and GFAP using CCK-8 assay, RT-qPCR, ELISA and Western blotting. SH-SY5Y neurons were co-cultured with U87 astrocytes treated with Aβ42 alone or in combination with SFN or SB203580 for 24 h, and the changes in Bax protein expression levels and viability of SH-SY5Y cells were examined. The effects of Aβ42, SFN, and their combination were also observed in astrocytes isolated from mouse brain tissues, and the indirect effects of astrocyte treatmentt on viability of the co-cultured primary neurons were assessed.

Results: The viability of U87 astrocytes increased significantly following treatment with 1.25 μmol/L Aβ42 but decreased after Aβ42 treatment above 5 μmol/L. SFN treatments for 24 h below 5 μmol/L did not significantly affect U87 cell viability. Aβ42 treatment significantly increased protein expressions of p-p38, p-p65 and GFAP, mRNA expression levels of IL-6 and TNF-α, and IL-6 and TNF-α levels in culture supernatant of U87 cells. SH-SY5Y cells co-cultured with Aβ42-treated U87 cells showed significantly increased protein expressions of Bax, and exhibited lowered viability following co-culture with 5 μmol/L Aβ42-treated U87 cells. The isolated mouse astrocytes showed lowered viability following Aβ42 treatment above 10 μmol/L, but SFN treatment below 5 μmol/L for 24 did not obviously affect the cell viability. The primary neurons co-cultured with Aβ42-treated mouse astrocytes showed significantly lower cell viability than those co-cultured with the astrocytes treated with Aβ+SFN or Aβ+SB203580.

Conclusions: SFN attenuates astrocyte-mediated neuron apoptosis by inhibiting the MAPK/NF-κB signaling pathway in Aβ42 oligomer-activated astrocytes.

Objectives: To investigate the protective effects of Poria cocos polysaccharide (PCP) against cyclophosphamide (CTX)-induced intestinal mucosal injury and its impact on gut flora and their metabolites in mice.

Methods: Adult BALB/C mice were randomized into normal control group, CTX model group, glutamine (positive control) group, and low-, medium- and high-dose PCP treatment groups. In all but the normal control group, the mice were subjected to modeling of CTX-induced intestinal mucosal injury by intraperitoneal CTX injections for 3 days, followed by treatment with gavage of normal saline, glutamine (300 mg/kg), or PCP at 75, 150, or 300 mg/kg for 7 consecutive days. The colonic expressions of tight junction proteins (occludin and ZO-1), serum endotoxin, D-lactate, and DAO levels, intestinal permeability, colon injury, and colonic cytokine levels (IL-4, IL-22, IL-17A, and IFN-γ mRNA) were assessed. Gut microbiota, short-chain fatty acids (SCFAs; mainly acetates and propionates) and colonic GPR41 expression were analyzed using 16S rRNA sequencing, GC-MS, and Western blotting, respectively. Fecal microbiota transplantation (FMT) experiment was conducted to validate the role of gut microbes in PCP-mediated repair of intestinal injuries.

Results: Compared with those in the model group, the mice treated with PCP showed significantly increased colonic occludin and ZO-1 expressions, reduced serum endotoxin, D-lactate and DAO levels, and lowered intestinal permeability with increased colonic expressions of IL-4, IL-22, IL-17A, and IFN-γ mRNA. PCP treatment obviously increased the abundance of Muribaculaceae, decreased Lactobacillus and Bacteroides, increased the contents of acetate and propionate in the colon, and upregulated colonic GPR41 expression. The results of FMT experiment confirmed the crucial role of gut microbes in PCP-mediated repair of CTX-induced intestinal injuries in mice.

Conclusions: PCP can protect against CTX-induced intestinal mucosal injury in mice possibly by modulating gut flora and SCFAs metabolism to enhance intestinal defense capacity.

Objectives: To evaluate the efficacy and safety of super electroconvulsive therapy (ECT) for treatment-resistant depression (TRD).

Methods: This cohort study was conducted among 292 patients with TRD, who received super ECT from December, 2024 to June, 2025. Eighty-eight of the patients received one electrical stimulation in each super ECT procedure (E1 group), 89 had 2 electrical stimulations (E2 group), and 39 had 3 electrical stimulations (E3 group). The correlation between depression, anxiety and sleep quality at baseline was analyzed. The patients were evaluated using 17-items Hamilton Depression Scale (HAMD-17) at 1, 3, and 6 months after the first super ECT session, and the treatment remission rate and response rate were compared among the 3 groups. The number of sessions and incidences of adverse events within 6 months were compared, and the EEG seizure duration at the first super ECT session was analyzed.

Results: Seventy-four patients (84.09%) in group E1, 76 (76.40%) in group E2, and 32 (82.05%) in group E3 achieved remission within 6 months after super ECT. The average number of treatment sessions was 2.13±1.44 in Group E1, 2.23±2.01 in Group E2, and 2.41±2.15 in Group E3 within 6 months. The baseline HAMA, HAMD-17 and PSQI scores were significantly correlated (P<0.001). The first seizure duration in E1 group was significantly longer than that in E2 and E3 groups (P<0.001). The rehospitalization rates were significantly higher in E2 group than in E1 group at 3 months (P=0.012) and 6 months (P=0.026). The short-term adverse effects included fever, headache/dizziness, general pain and dry mouth.

Conclusions: Super ECT is safe and effective for treatment of TRD patients with a total seizure duration longer than 180 s. The number of electrical stimulations in each treatment session does not significantly affect the therapeutic efficacy of super ECT.

Objectives: To explore the transcriptomic characteristics of the endplate cartilage of the cervical intervertebral disc in cervical spondylosis (CS) and the effects of acupotomy on expressions of fibroblast growth factor 18 (FGF18)/protein kinase B (Akt) axis key molecules.

Methods: Transcriptomic analyses were performed using bioinformatics methods based on the GEO database. In the animal experiment, 24 New Zealand rabbits were randomized equally into control, CS model, and acupotomy groups. In the latter two groups, CS models were established followed 7 days later by acupotomy intervention (once a week for 3 weeks) or no particular treatment. Histopathological changes and cell apoptosis in the intervertebral discs were examined with HE staining and TUNEL assay, and the mRNA expressions of FGF18, FGFR3, and Akt in the intervertebral discs were detected using RT-qPCR; the localization and expressions of FGF18, p-Akt, and Akt proteins were examined with immunohistochemistry.

Results: The endplate cartilage in CS exhibited numerous differentially expressed genes enriched in the PI3K-Akt signaling, calcium signaling, and Rap1 signaling pathways. CS rabbits showed obvious changes in the cervical spine curvature and joint degenerations, changes in cervical intervertebral disc texture, thinning of the annulus fibrosus, shrinkage or even absence of the nucleus pulposus, and increased apoptotic cells in the endplate cartilage, which were all obviously alleviated after acupotomy. No significant differences were found in the mRNA expressions of FGF18, FGFR3, and Akt in the cervical intervertebral discs among the 3 groups. Acupotomy significantly increased FGF18 and p-Akt protein expressions and reduced the Akt/p-Akt ratio in the cervical endplate cartilage of CS rabbits.

Conclusions: The cervical endplate cartilage of CS show numerous differentially expressed genes. Acupotomy may delay degenerative changes of the intervertebral discs and improves CS by activating the FGF18/Akt axis to reduce apoptosis of endplate cartilage cells.

Objectives: To explore the association between the use of β-blockers and the risks of all-cause mortality and major adverse cardiovascular events (MACEs) in patients with stable coronary artery disease (SCAD) after percutaneous coronary intervention (PCI).

Methods: We performed secondary analyses of the data of 55 SCAD patients receiving post-PCI β-blocker treatment and 149 patients without post-PCI β‑blockers (control group) from the Dryad database. The clinical and coronary artery disease characteristics of the patients were analyzed, and propensity score matching was used to compare all-cause mortality and MACEs (including cardiovascular death, non-fatal myocardial infarction and non-fatal stroke) between the two groups.

Results: The overall patients (69.6% were male) had a mean age of 72.6±10.3 years with a median follow-up time of 783 days. A total of 18 patients (8.8%) died, and MACEs occurred in 19 patients (9.3%), including cardiovascular death in 6 cases (2.9%), non-fatal myocardial infarction in 3 cases (1.5%) and non-fatal stroke in 11 cases (5.4%). In the β‑blocker group, deaths occurred in 5 cases (9.1%), and MACEs in 4 cases (7.3%), including 2 cases with cardiovascular death (3.6%) and 2 cases with non-fatal stroke (3.6%). Kaplan-Meier survival curve analysis showed that the use of β-blockers after PCI was not associated with a reduced all-cause mortality (8.7% vs 9.1%, log-rank P=0.870) or incidence of MACEs (10.1% vs 7.3%, log-rank P=0.510) either before or after adjusting for age, sex, aspartate aminotransferase, estimated glomerular filtration rate, left ventricular ejection fraction, and history of atrial fibrillation (HR=0.81, 95% CI: 0.24-2.72; HR=0.62, 95% CI: 0.22-1.69). No significant differences were found in all-cause death or MACEs between the two groups after propensity score adjustment, matching, or IPTW inverse probability weighting (all P>0.05).

Conclusions: Routine use of β-blockers after PCI does not reduce the incidence of all-cause death or MACEs in patients with SCAD.

Objectives: To monitor the changes in oxygenation levels of rat kidneys under step oxygen stimulation by high temporal resolution dynamic T₂* weighted planar echo imaging (T₂*W-EPI).

Methods: Step oxygen stimulation was applied to SD rats (n=10) in the sequence of 2 min of hyperoxia (100% O₂) -10 min of hypoxia (10% O₂) -10 min of hyperoxia (100% O₂). Dynamic MRI data of the kidneys of multi-echo gradient echo (mGRE) sequence and gradient echo-planar imaging (EPI) sequence were continuously acquired on a 9.4T small animal magnetic resonance scanner. The time resolution of the two sequences were 9 s and 1 s, respectively. A second-order step response model was established for the dynamic time series curves of different regions of interest (ROIs) in rat kidneys, and the parameters of the step response model were obtained, including time delay ∆t, natural frequency ωn, damping constant D and oscillation period T. The performance of two MRI imaging methods with different temporal resolution in response to the step oxygen stimulation in the kidneys was compared.

Results: Compared with the control experiment results of mGRE, the dynamic T₂*W-EPI technology proposed in this study increased the temporal resolution of monitoring renal step oxygen stimulation by 8 folds and improved the goodness of fit of the step response model. The model showed a shorter time delay ∆t (shortened by 29.4%, 42.6%, 56.4%, and 47.4%, respectively, in the CO, OSOM, ISOM and IM), a larger natural frequency ωn (increased by 21.1%, 28.6%, 52.2%, and 61.9%, respectively), and oscillation of each ROI (damping constant D<1) under the step oxygen stimulation.

Conclusions: In a step oxygen stimulation model of rat kidneys, the high temporal resolution dynamic T₂*W-EPI technique proposed in this study is capable of real-time monitoring of the changes in renal oxygenation levels for detection of abnormal renal conditions.

Objectives: To investigate the role of transmembrane protein EVA1A in liver lipid metabolism and development of non-alcoholic fatty liver disease (NAFLD).

Methods: Eight-week-old male ob/ob mice were randomized into control group injected with AAV null vector via the tail vein (AAV-null group) and AAV-Eva1a group injected with recombinant vector AAV-Eva1a (n=8). HepG2 cells transfected with the lentiviral vector LV-EVA1A or the null vector were induced with oleic acid to construct a cell model of NAFLD. The expression levels of EVA1A, lipid metabolism-related and autophagy-related genes in mouse livers were detected with RT-qPCR, Western blotting, and immunofluorescence staining, and lipid accumulation in mouse livers and blood and in the treated cells was examined with HE and Oil Red O staining and lipid detection kits. Serum levels of ALT, AST, IL-6, IL-1β, and TNF-α of the mice were detected, and hepatic lipophagy was observed with transmission electron microscopy.

Results: The mouse livers in AAV-Eva1a group and LV-EVA1A-transfected cells showed significantly increased expression levels of EVA1A mRNA and protein. The liver weight and coefficient and lipid deposition of the mice with AAV-Eva1a injection and triglyceride (TG) content in LV-EVA1A-transfected cells were significantly decreased. The mice in AAV-Eva1a group showed significantly reduced serum total cholesterol, LDL-C, and HDL-C levels and hepatic TG levels with lowered serum levels of ALT, AST, IL-6 and TNF‑α. In both mouse livers in AAV-Eva1a group and LV-EVA1A-transfected HepG2 cells, acetyl-CoA carboxylase, fatty acid transport protein, and diacylglycerol acyltransferase expressions were all significantly decreased and adipose triglyceride lipase increased. Hepatic lipophagy, autophagosome numbers and LC3-II and ATG5 expressions were enhanced and p62 expression was lowered in the mice in AAV-Eva1a group and LV-EVA1A-transfected cells.

Conclusions: EVA1A overexpression alleviates fatty liver and inflammation in ob/ob mice by regulating lipid metabolism-related genes and enhancing lipophagy to promote clearance of accumulated hepatic lipids.

Objectives: To investigate the mechanism of poricoic acid A (PAA) for alleviating dextran sulfate sodium (DSS)-induced colitis in mice.

Methods: Eighteen C57BL/6 mice were randomly divided into control group, DSS-induced colitis model group, and PAA intervention (10 mg/kg) group. The changes in body weight, colon length, disease activity index (DAI), and histopathological scores of the mice were evaluated. In a DSS-induced Caco-2 cell model, the changes in expressions of ZO-1, claudin-1, Bcl-2, Bax, cleaved caspase-3, LC3-II/I, and P62 were detected. Molecular docking and Western blotting were used to analyze the mechanisms underlying the ameliorating effect of PAA on DSS-induced colitis.

Results: In the mouse models of DSS-induced colitis, PAA significantly ameliorated DSS-induced weight loss, colon shortening, and elevation of DAI scores while reducing colonic IL-1β and TNF-α levels. HE staining showed that PAA obviously alleviated colonic crypt damage, reduced inflammatory cell infiltration, and lowered histopathological scores of the colon. AB-PAS staining revealed significantly increased goblet cell counts in PAA-treated mice compared to those in DSS group. In DSS-induced Caco-2 cells, PAA treatment effectively inhibited DSS-induced downregulation of the tight junction proteins, reduced Bax and cleaved caspase-3 expressions, increased Bcl-2 expression and the LC3-II/I ratio, and decreased P62 expression. Mechanistic study suggested that PAA targeted the AMPK/mTOR pathway to activate autophagy and suppress cell apoptosis.

Conclusions: PAA protects intestinal barrier function and alleviates DSS-induced colitis in mice by activating AMPK/mTOR-mediated autophagy and inhibiting intestinal epithelial cell apoptosis.