南方医科大学学报杂志最新文献

Objectives: To quantitatively analyze setup errors of 4 immobilization devices in precision radiotherapy for prostate cancer, their accuracy differences, and the factors affecting their setup precisions.

Methods: We conducted a retrospective analysis of 240 prostate cancer patients undergoing image-guided radiotherapy at Sun Yat-sen University Cancer Center from May, 2016 to May, 2024. According to the immobilization devices used, the patients were divided into 1.2 m vacuum bag group (n=60), 1.8 m vacuum bag group (n=60), Orfit frame group (n=60), and customized prone board group (n=60). All the patients received pre-treatment cone-beam CT (CBCT) scans, and setup errors in the right-left (RL), superior-inferior (SI), and anterior-posterior (AP) directions were obtained through XVI system grayscale registration. Further subgroup analyses were performed based on patient stratifications by lymph node irradiation status (n=120 each), age (<65 years, n=80; ≥65 years, n=160), and BMI (BMI<24 kg/m², n=120; BMI≥24 kg/m², n=120).

Results: The setup errors differed significantly among the 4 groups in three-dimensional directions (P<0.05). The customized prone board group showed minimal errors in the RL (0.02±0.25 cm) and SI (0.01±0.32 cm) directions, but demonstrated the largest error in the AP direction (-0.28±0.36 cm). The patients with lymph node irradiation had significantly greater AP directional errors (-0.22±0.36 cm) than those without (-0.01±0.43 cm; P<0.001). BMI showed a negative correlation with SI directional errors (R=-0.45, P<0.001), while age was not significantly correlated with the setup errors (P>0.05).

Conclusions: The customized prone board demonstrates clinically significant advantages for its high setup accuracies in RL and SI directions in spite of its systematic AP directional errors. The setup accuracy in the SI direction is especially important for patients with lymph node irradiation or low BMI. Our findings provide quantitative evidence for immobilization device selection and individualized optimization of precision radiotherapy for prostate cancer.

Objectives: To develop and validate a risk prediction model for cognitive impairment in community-dwelling elderly individuals in China.

Methods: This cross-sectional study was based on data from the 2011 China Health and Retirement Longitudinal Study (CHARLS), and the data of 2228 individuals aged ≥60 years were analyzed. The participants were randomly divided into a training set (n=1560) and an internal validation set (n=668) in a 7∶3 ratio. Thirty-eight candidate variables were collected, covering sociodemographic characteristics, lifestyle and behavioral habits, chronic disease history, physical function, and self-rated health status. Feature selection was performed using the least absolute shrinkage and selection operator (LASSO) regression, followed by multivariate logistic regression to identify independent risk factors for cognitive impairment. A nomogram was constructed based on these factors, its discrimination power and calibration were assessed using the receiver operating characteristic (ROC) curve and calibration plot, respectively, and its clinical utility was evaluated using decision curve analysis (DCA).

Results: Age, years of education, alcohol consumption, systolic blood pressure, grip strength, and depressive symptoms were identified as independent predictors of cognitive impairment in Chinese elderly individuals. The area under the ROC curve of the constructed nomogram was 0.839 (95% CI: 0.814-0.864) in the training set and 0.840 (95% CI: 0.801-0.879) in the validation set, indicating good predictive performance of the model. The calibration plots demonstrated good agreement between the predicted and observed outcomes, and the DCA showed good clinical utility of the model.

Conclusions: The nomogram developed in this study based on LASSO-selected predictors demonstrates high accuracy, discrimination power, and potential clinical applicability to facilitate early identification and intervention of cognitive impairment among rural elderly individuals in China.

Objectives: To investigate the association of preoperative serum magnesium (sMg) level with postoperative delirium (POD) in elderly surgical patients and the mediating role of systemic inflammation.

Methods: This retrospective cohort study was conducted among 12 876 patients aged ≥65 years undergoing non-cardiac, non-neurological surgeries at Chinese PLA General Hospital between January, 2014 and December, 2021. Preoperative sMg and C-reactive protein (CRP) levels were measured within 30 days before surgery. POD was identified within 7 days postoperatively using structured chart review based on the Confusion Assessment Method. Multivariate logistic regression and restricted cubic spline (RCS) models were used to evaluate the association between sMg and POD. Mediation analysis with structural equation modeling was used to quantify the indirect effect of CRP after adjusting for the confounding factors.

Results: POD was identified in 685 (5.3%) of the patients. A significant nonlinear association was observed between preoperative sMg levels and POD risk, and POD incidence was the lowest in patients with sMg levels of 0.90-0.94 mmol/L. Compared with those in the 4th quintile, the patients in the lowest quintile exhibited a markedly increased risk of POD (OR=1.81, 95% CI: 1.41-2.35) even after adjustment for multiple confounding factors. Mediation analysis suggested that CRP explained 17.1% of the total effect of sMg on POD risk, and a stronger mediating effect was observed in cancer as compared with the non-cancer patients (24.1% vs 11.9%). Subgroup analyses revealed a significant nonlinear relationship between sMg and POD particularly in cancer patients and patients beyond 75 years of age.

Conclusions: Preoperative sMg level is independently associated with an increased POD risk in elderly patients, mediated partly by systemic inflammation. sMg may serve as a modifiable biomarker for early risk stratification and prevention for POD in perioperative care.

Objectives: To explore therapeutic mechanism of Hugan Tang (Hugan Decoction, HGT) for alleviating non-alcoholic fatty liver disease (NAFLD) in rats.

Methods: Network pharmacology analysis was used to predict the active components of HGT against NAFLD and their potential targets, and the core targets were identified using the protein-protein interaction network, followed by GO and KEGG pathway enrichment analyses. A rat model of high-fat diet (HFD)-induced NAFLD was used to test the effects of saline, silymarin, and low-, moderate-, and high-dose HGT on serum levels of ALT, AST, LDL, LDH, TG and TC, liver histopathology, and protein and mRNA expressions of ACC1, FASN, AMPK and m-TOR. In free fatty acid (FFA)-induced HepG2 cells, the effects of blank and HGT-medicated sera, compound C (an AMPK inhibitor), and MHY1485 (a mTOR agonist) were tested on cell viability, intracellular lipid deposition, TC and TG levels, and expressions of ACC1, FASN, AMPK and m-TOR.

Results: We identified 130 active components in HGT, 267 common targets with NAFLD, and 53 core gene nodes, nearly half of which were involved in lipid metabolism. HGT treatment of NAFLD was closely associated with lipid and atherosclerosis signaling, insulin resistance signaling, and AMPK signaling. In rat models of NAFLD, HGT significantly alleviated liver injury and lipid accumulation, and suppressed mRNA and protein expressions of ACC1 and FASN. In FFA-induced HepG2 cells, HGT-medicated serum obviously reduced TG and TC levels and inhibited ACC1 and FASN mRNA and protein expressions. The results of in vitro and in vivo experiments both demonstrated that HGT activated the AMPK/mTOR signaling pathway by promoting p-AMPK expression and suppressing p-mTOR expression, and its regulatory effects on p-AMPK, p-mTOR, ACC1, and FASN were differentially modulated by compound C and MHY1485.

Conclusions: HGT alleviates NAFLD in rats by activating the AMPK/m-TOR signaling pathway and reducing lipid synthesis.

Objectives: To explore the role of Chi3l1 in human umbilical cord mesenchymal stem cell (hUC-MSCs) therapy of type 1 diabetes.

Methods: hUC-MSCs with stable Chi3l1 knockdown (sh-Chi3l1-MSCs) were constructed using a lentiviral vector and characterized by flow cytometry and adipogenic and osteogenic induction. In adult C57BL/6J mouse models of streptozotocin-induced T1DM, the therapeutic effects of sh-NC-MSCs and sh-Chi3l1-MSCs grafting were evaluated by observing changes in clinical manifestations, blood glucose, body weight and pancreatic tissue pathologies. Insulin content and macrophage infiltration in the islets were detected using immunohistochemistry and immunofluorescence staining. The effects of these two stem cells on induced polarization of co-cultured mouse bone marrow macrophages were assessed using flow cytometry by detecting the mRNA expressions of iNOS, Arg-1, TNF-α, IL-6, IL-10, IL-13, and IL-1β using qPCR.

Results: The constructed sh-Chi3l1-MSCs retained the characteristics of MSCs but showed reduced therapeutic efficacy in T1DM mice. Immunofluorescence staining showed that the number of macrophages in the pancreatic tissue of the mice treated with sh-Chi3l1-MSCs was higher than that in MSCs treatment group. In the co-culture experiments, sh-Chi3l1-MSCs exhibited a lowered capacity to suppress M1 polarization of the macrophages and a reduced efficacy to promote differentiation of M2-type macrophage subset. Analysis with qPCR showed that the expressions of M1 macrophage marker iNOS and the inflammatory factors TNF-α, IL-6, and IL-1β increased, while the expressions of M2 macrophage marker Arg-1 and the cytokines IL-13 and IL-10 were decreased significantly in sh-Chi3l1-MSCs group.

Conclusions: In T1DM mouse models, hUC-MSCs mitigate inflammatory responses by suppressing the production of pro-inflammatory M1-type macrophages via Chi3l1.

Objectives: To investigate the molecular mechanism of helicid for improving depressive-like behaviors in rats exposed to chronic unpredictable mild stress (CUMS).

Methods: SD rats were randomly divided into normal control group (n=20) and CUMS group (n=70) to receive no stimulation and mild unpredictable stress for 6 weeks, respectively. After successful modeling, CUMS rats were further divided into 7 subgroups for intracerebroventricular injection with saline, adeno-associated virus (AAV) vector, or AAV carrying si-NCALD (NCALD silencing experiment, n=10); or intracerebroventricular injection with saline, saline with daily helicid gavage, AAV vector with helicid gavage, or NCALD-overexpressing AAV with helicid gavage (NCALD overexpresison experiment, n=10). The depressive state of the rats was evaluated by assessing changes in body weight, sucrose preference, and open field test. The expressions of NCALD, sGCα1, sGCβ1, PKG1/2, and cleaved-caspase 3 in the hippocampus of the rats were detected by Western blotting, and hippocampal cGMP level was determined with ELISA.

Results: Compared with the normal control rats, CUMS rats showed significantly increased hippocampal expressions of NCALD and cleaved caspase-3 and abnormal activation of the sGC/cGMP/PKG pathway. Silencing NCALD by intracerebroventricular injection of AAV-si-NCALD significantly reduced cleaved caspase-3 and inhibited sGC/cGMP/PKG pathway activation in the hippocampus, and improved depressive-like behaviors of the rats. Helicid treatment produced similar effects, but its effect was abolished by intracerebroventricular injection of NCALD-overex-pressing AAV.

Conclusions: Helicid relieves depressive-like behaviors in CUMS rats by downregulating NCALD, inhibiting abnormal sGC/cGMP/PKG activation, and reducing hippocampal apoptosis.

Objectives: To identify the differentially expressed genes in obese asthma versus non-obese asthma and evaluate the effect of acupuncture on chronic airway inflammation in obese mice with asthma.

Methods: The key genes of obesity-related asthma were screened using GSE110551 dataset from the GEO database, and the characteristic genes were selected from the genes with the highest correlation with T cells using Lasso regression and SVM feature selection algorithms. Fifty C57BL/6J mice (5-6 weeks old) were randomized equally into 5 groups, including a normal feeding (control) group, a high-fat feeding group, and 3 high-fat feeding and ovalbumin sensitization groups with intraperitoneal injections with saline or dexamethasone (DEX), or treated with acupuncture. Western blotting, qPCR, and flow cytometry were used to analyze the changes in the expressions of the key genes and inflammation in the airway of the mice.

Results: FAM126B and VNN1 were identified as the characteristic genes in obesity-related asthma for subsequent analysis. The mice with high-fat feeding and ovalbumin sensitization showed the highest expression levels of Vnn1 and FAM126B among the 5 groups, with also significantly decreased Treg cell percentage and obvious inflammatory cell infiltration in the lungs. Treatment with DEX and acupuncture both significantly decreased the number of infiltrating inflammatory cells and increased the percentage of Treg cells in airway of the mouse models of obesity-related asthma. HIF-1α was identified as a key regulatory factor for asthmatic inflammation, and its expression level was significantly increased in the asthmatic mouse models but obviously lowered after acupuncture treatment or dexamethasone therapy.

Conclusions: Vnn1 and FAM126B may serve as the key therapeutic targets for treatment of obese asthma patients. Acupuncture treatment may downregulate airway HIF-1α by reducing the expressions of Vnn1 and FAM126B and increasing the number of Treg cells.

Objectives: We propose an efficient deep learning model to improve the classification accuracy in automatic classification tasks of 12-lead electrocardiogram (ECG) signals.

Methods: We designed a new ResLSTM-TemporalSE network architecture by incorporating a multi-layer Residual Long Short-Term Memory (ResLSTM) structure and introducing skip connections between LSTM layers to establish residual learning pathways for the temporal features. A temporal attention mechanism was integrated into the traditional Squeeze-and-Excitation (SE) module to enhance channel-wise feature representation while capturing long-term temporal dependencies within ECG signals, thereby an efficient hierarchical feature extraction framework was constructed. The model was validated using the public CPSC2018 dataset and a private clinical dataset from the Seventh Affiliated Hospital of Southern Medical University.

Results: The experimental results demonstrated that the model achieved a classification accuracy of 99.70% on the CPSC2018 test set, with precision, recall, and F1-score values of 0.9966, 0.9370, and 0.9653, respectively. On the private clinical dataset, it attained an accuracy of 82.77%, with precision, recall, and F1-score values of 0.6811, 0.8961, and 0.7723. Ablation studies confirmed the significant contributions of both the residual connections and the temporal attention module to model performance.

Conclusions: The ResLSTM-TemporalSE model effectively integrates spatiotemporal features of the ECG signals and demonstrates superior classification performance on the CPSC2018 benchmark while maintaining strong generalization capabilities in real-world clinical settings. This framework provides a robust solution for automated ECG analysis and holds significant promise for clinical applications.

Objectives: To explore the therapeutic mechanism of Fuzheng Xiaoyan (FZXY) Granules for relieving cancer-related fatigue (CRF) during chemotherapy in breast cancer patients based on the traditional Chinese medicine (TCM) theory of "Fuzheng Quxie" (supporting healthy qi and eliminating pathogens).

Methods: Ninety CRF patients with breast cancer and Zhengxu Duyu syndrome were randomized equally into control group with chemotherapy and symptomatic treatment and study group with additional treatment with FZXY Granules, and their Piper Fatigue Scale (PFS), Karnofsky Performance Status (KPS), and TCM syndrome scores were compared. Network pharmacology analysis was used to identify the active components in FZXY Granules, the drug targets, and disease-related targets. Protein-protein interaction (PPI) network was constructed followed by enrichment analysis. Molecular docking study was conducted to explore the interactions between quercetin and the core targets. In a CRF mouse model bearing breast cancer xenograft, the effects of saline and FZXY Granule gavage were observed by assessing motor function, expressions of AKT1, p-AKT1, BCL-2, and BAD in the gastrocnemius muscle, and serum levels of IL-6 and IL-1β.

Results: The patients receiving FZXY Granules treatment showed significantly improved PFS, KPS, and TCM syndrome scores compared with the baseline levels and those in the control group (P<0.05). Fifty-seven overlapping drug-disease targets were screened, and 5 core targets were identified. Quercetin exhibited strong binding to AKT1 and acted likely via the apoptosis pathways. In the CRF mouse models, FZXY Granules obviously improved motor function of the mice, reversed abnormal apoptosis-related protein expressions in the gastrocnemius muscle, and reduced serum IL-6 and IL-1β levels.

Conclusions: FZXY Granules alleviate CRF and improve TCM symptoms and quality of life of breast cancer patients during chemotherapy possibly by suppressing skeletal muscle cell apoptosis via regulating the AKT1/BAD/BCL-2 pathway and reducing IL-6 and IL-1β levels.

Objectives: To investigate the effect of overwork on myocardial energy metabolism in mice.

Methods: Thirty-two C57BL/6J mice were randomized equally into a control group and 3 overwork groups with overwork for 2, 4, and 6 weeks (W2, W4, and W6 groups, respectively). The mice in overwork groups were subjected to daily forced water standing and restraint. The changes in body weight and general condition of the mice were observed weekly. After successful modeling, the mice were examined for changes in echocardiography, blood glucose/lipid profiles, myocardial pathologies, myocardial TG and ATP levels, and expressions in CD36, GLUT1, CPT1B, PPARα, PFKM, and PKM2 using immunohistochemistry, RT-qPCR or Western blotting.

Results: The mice with prolonged overwork exhibited reduced activity with hair loss, dull fur, and slowed body weight gain without significant changes in cardiac index or function. Blood glucose levels increased significantly in W2 and W4 groups but decreased in W6 group. Serum TG level increased significantly while TC, HDL, and LDL decreased in W4 and W6 groups. HE staining revealed myocardial swelling, disorganization, and vacuolation in the mouse models. Myocardial TG was elevated in W4 and W6 groups and ATP level decreased in W6 group. The mRNA and protein expressions of CPT1B and PPARα were downregulated in W4 and W6 group, and CD36 expression increased significantly in W4 group. GLUT1 and PFKM/PKM2 expressions decreased obviously in W2 group but increased in W4 and W6 group compared with that in W2 group.

Conclusions: Short-term overwork causes elevation of blood glucose and suppresses glycolysis in mice, while prolonged overwork reduces glucose, increases TG, impairs fatty acid oxidation, and limits glycolytic compensation to eventually result in myocardial damage, lipid accumulation, and ATP deficiency.