Nan Fang Yi Ke Da Xue Xue Bao
· 2026 Jun · PMID 42343853
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OBJECTIVES: To develop an efficient model for detecting abnormal heart sounds and providing technical support for automated phonocardiogram (PCG) analysis. METHODS: The proposed model, MS-DTNet, integrates multi-scale co...OBJECTIVES: To develop an efficient model for detecting abnormal heart sounds and providing technical support for automated phonocardiogram (PCG) analysis. METHODS: The proposed model, MS-DTNet, integrates multi-scale convolution and a dual-tower attention mechanism. The network employs depthwise separable convolution to achieve a lightweight architecture, applies multi-scale convolution to capture features across receptive fields in parallel, utilizes a dual-tower structure to extract both short- and long-term temporal information, and incorporates a flipped-attention mechanism to further enhance feature representation. Experiments were conducted on the public CinC2016 dataset using 5-fold cross-validation. RESULTS: In the abnormal heart sound classification task, the proposed model achieved an average accuracy of 94.49%, a specificity of 93.44%, a sensitivity of 95.49%, a precision of 93.81%, F1-score of 94.64%, and ROC-AUC of 98.65%, outperforming all the comparison models. CONCLUSIONS: The proposed MS-DTNet model demonstrates excellent performance in PCG classification and provides technical assistance for multi-source heart sound analysis and clinical decision support.
Nan Fang Yi Ke Da Xue Xue Bao
· 2026 Jun · PMID 42343852
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OBJECTIVES: To develop a bidirectional feature-mapping classification model for differential diagnosis of pneumonia. METHODS: We collected chest X-ray (CXR) images from 1457 patients with pneumonia and 1456 healthy indiv...OBJECTIVES: To develop a bidirectional feature-mapping classification model for differential diagnosis of pneumonia. METHODS: We collected chest X-ray (CXR) images from 1457 patients with pneumonia and 1456 healthy individuals. Radiomic features extracted from the segmentation masks using PyRadiomics were mapped into a latent shared space to construct the classification model using the bidirectional feature mapping classification model based on multi-constrained latent representation learning. The performance of the constructed model for differential diagnosis of pneumonia was evaluated using 5-fold cross-validation and compared with other feature-based classification models. Decision curve analysis was used for evaluating clinical utility of the model, and ablation experiments were performed to assess the contribution of each constraint module. The importance of the radiomics features was interpreted using the SHAP method, and a two-dimensional visualization experiment of the low-dimensional latent features obtained through the proposed mapping method was conducted to verify the feasibility and effectiveness of the model. RESULTS: The 5-fold cross-validation results showed that the proposed classification model had a positive predictive value of 0.796, a negative predictive value of 0.830, a specificity of 0.784, a sensitivity of 0.830, an accuracy of 0.811, and an area under the ROC curve of 0.893 for differential diagnosis of pneumonia. Decision curve analysis demonstrated a high net clinical benefit of the model within acceptable threshold probabilities. Ablation studies confirmed the essential role of the multi-constraint module, and the SHAP analysis revealed that the model focused primarily on clinically meaningful and medically interpretable features. The feature mapping method exhibited excellent performance in visual experiments to confirm the effectiveness of the proposed model. CONCLUSIONS: The proposed bidirectional feature mapping classification model demonstrates strong discriminative capability and high potential for differential diagnosis of pneumonia and shows obvious advantages over other classification models in pneumonia classification tasks.
Zhang M, Wu D, Lin J
… +5 more, Lü Y, Zhou L, Zhen X, Zhou H, Qin G
Nan Fang Yi Ke Da Xue Xue Bao
· 2026 Jun · PMID 42343851
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OBJECTIVES: To construct a Transformer-based multimodal data encoding model for predicting hospital-acquired infections (HAI). METHODS: Laboratory test data of 300 000 patients were extracted from the publicly available...OBJECTIVES: To construct a Transformer-based multimodal data encoding model for predicting hospital-acquired infections (HAI). METHODS: Laboratory test data of 300 000 patients were extracted from the publicly available MIMIC-IV database. The laboratory data of 1172 patients and chest X-ray images from 274 of these patients were collected from Nanfang Hospital. A novel Transformer-based encoding model was developed to process the data, which was then connected to a machine learning classifier for predicting HAI. The radiomic and deep learning features were extracted from the chest X-ray images for predicting ventilator-associated pneumonia (VAP). These imaging features were subsequently integrated with the laboratory test data using a feature fusion algorithm. The model performance was evaluated by assessing the accuracy, the area under the ROC curve (AUC), sensitivity, and specificity. The proposed algorithm was quantitatively compared against traditional machine learning classifiers to validate its effectiveness and feasibility. RESULTS: The results demonstrated that the model developed in this study achieved an AUC of 0.989 in the internal validation set. In the external validation set, the optimal model for predicting HAI attained an AUC of 0.98, and following the integration of imaging features, the optimal model reached an AUC of 0.93 in the VAP prediction task, demonstrating superior performance over the baseline models. CONCLUSIONS: The Transformer-based model for processing laboratory test data has excellent predictive capability and good clinical applicability for HAI prediction with also good performance for predicting VAP.
Fang L, Xie D, Huang D
… +4 more, DU Q, DU S, Zhu T, Sun H
Nan Fang Yi Ke Da Xue Xue Bao
· 2026 Jun · PMID 42343850
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OBJECTIVES: To validate the non-inferiority of plant-based pigment patches as surface markers for postoperative radiotherapy localization in breast cancer, evaluate their accuracy, durability and safety, and identify the...OBJECTIVES: To validate the non-inferiority of plant-based pigment patches as surface markers for postoperative radiotherapy localization in breast cancer, evaluate their accuracy, durability and safety, and identify the factors influencing pigment fading to determine the patients eligible for these patches. METHODS: In this randomized controlled trial, 80 patients receiving their first course of postoperative radiotherapy for breast cancer were randomly assigned in a 1:1 ratio to plant-based pigment patch group (trial group) or conventional laser microdot tattoo group (control group). The primary outcome was 3-dimensional setup error (non-inferiority margin: 0.7 mm). The secondary outcomes included uniaxial errors, re-marking frequency, skin adverse events, patient comfort, and healthcare satisfaction. Linear mixed-effects models and Cox regression were used for data analyses. RESULTS: The baseline characteristics of the patients were balanced between the two groups. The trial group demonstrated non-inferiority to the control group in setup accuracy (3-dimensional error: 3.12±1.14 mm 3.05±0.98 mm; mean difference: 0.07 mm; 95% : -0.31 to 0.45; upper limit <0.7 mm). No significant differences were observed in the uniaxial errors. Patient comfort scores were significantly higher in the trial group (4.23±0.65 0.15±0.82, <0.001). The incidence of skin adverse events was zero in the trial group but 12.5% in the control group (<0.05). Multivariable Cox regression identified oily skin (HR=2.78, <0.001), frequent sweating (HR=3.02, <0.001), frequent washing (HR=1.42, <0.05), and a high BMI (HR=1.32, <0.05) as independent risk factors for faster pigment fading, while the use of a protective agent was a protective factor (HR=0.47, =0.019). CONCLUSIONS: Plant-based pigment patches are non-inferior to conventional laser microdots and offer comparable positioning accuracy with superior comfort and safety.
Shi X, Chen T, Gao J
… +6 more, Wu M, Li R, Su K, Lü Z, Song X, Feng X
Nan Fang Yi Ke Da Xue Xue Bao
· 2026 Jun · PMID 42343849
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OBJECTIVES: To investigate the protective effects of sera from rats receiving electroacupuncture (EA) against oxygen and glucose deprivation/reoxygenation (OGD/R) injury in HT22 neurons and explore the involvement of the...OBJECTIVES: To investigate the protective effects of sera from rats receiving electroacupuncture (EA) against oxygen and glucose deprivation/reoxygenation (OGD/R) injury in HT22 neurons and explore the involvement of the PI3K/Akt signaling pathway in this protective mechanism. METHODS: Bioinformatics analysis was performed using public databases to identify stroke-related pathways. A rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) were treated with EA at "Shenting" and "Baihui" to prepare EA rat serum. HT22 neurons were subjected to OGD/R and treated with MCAO rat serum, EA rat serum, LY294002, or EA rat serum combined with LY294002. The changes in cell viability, apoptosis, and neuronal morphology were assessed using CCK-8 assay, TUNEL staining, and Nissl staining. Western blotting was used to detect PI3K/Akt phosphorylation and the expressions of the downstream proteins (p-mTOR/mTOR and Bcl-2) and synaptic proteins (NMDAR1 and PSD-95); the mRNA expressions of PI3K, Akt, NMDAR1, and PSD-95 were detected using RT-qPCR. RESULTS: HT22 neurons with OGD/R injury treated with MCAO rat serum showed significantly decreased cell viability, increased apoptosis, and impaired neuronal morphology, which were obviously improved following treatment with EA rat serum but aggravated after LY294002 treatment. The protective effect of EA rat serum was significantly attenuated by application of LY294002. HT22 neurons treated with MCAO rat serum showed decreased p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR ratios with lowered expressions of Bcl-2, NMDAR1 and PSD-95, which were obviously upregulated by EA rat serum treatment but reduced after LY294002 treatment. The cells with the combined treatment showed intermediate expression levels of these molecules at both the mRNA and protein levels. CONCLUSIONS: Serum from rats receiving EA at "Shenting" and "Baihui" shows a protective effect against OGD/R injury in HT22 neurons, mediated possibly by activation of the PI3K/Akt signaling pathway and its downstream effectors and upregulation of synaptic plasticity-related molecules.
Huang W, Yan H, Li S
… +4 more, Wu H, Cai Y, Han Z, Tang S
Nan Fang Yi Ke Da Xue Xue Bao
· 2026 Jun · PMID 42343848
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OBJECTIVES: To investigate the impact of HIV-1 genotypes and population mobility on HIV-1 transmission in Guangzhou to obtain evidence for devising precision prevention and control strategies. METHODS: Demographic data a...OBJECTIVES: To investigate the impact of HIV-1 genotypes and population mobility on HIV-1 transmission in Guangzhou to obtain evidence for devising precision prevention and control strategies. METHODS: Demographic data and HIV-1 pol sequences were obtained from 6783 newly diagnosed people living with HIV (PLWH) in 2008-2020 in Guangzhou, including 24.0% local Guangzhou residents, 0.9% mobile Guangzhou residents, 56.4% local non-Guangzhou residents, and 18.6% mobile non-Guangzhou residents. HIV-1 genotypes were determined and molecular transmission networks were constructed using HIV-TRACE. Degree centrality and multinomial logistic regression were used to identify the key characteristics of the PLWH and risk factors of HIV-1 transmission. RESULTS: Among the PLWH, the dominated HIV-1 genotypes were CRF07_BC (39.6%), CRF01_AE (33.0%), and CRF55_01B (11.9%), and 43.3% of the PLWH formed 596 transmission clusters. Compared with subtype B, CRF01_AE (aOR=1.384, 95% : 1.072-1.798), CRF07_BC (aOR=2.462, 95% : 1.911-3.192), CRF55_01B (aOR=3.209, 95% : 2.424-4.271), and CRF59_01B (aOR=2.149, 95% : 1.437-3.219) were more likely to cluster. Population mobility was not associated with overall HIV-1 transmission, and local Guangzhou residents were more likely to be involved in CRF08_BC transmission (aOR=4.241, 95% : 1.494-12.790), whereas migrants had lower odds of transmitting CRF01_AE (aOR=0.740, 95% : 0.576-0.946) and subtype B (aOR=0.429, 95% : 0.182-0.922). The characteristics of high-risk individuals for HIV-1 transmission included local Guangzhou residents (aOR=1.390, 95% 1.141-1.695), men (aOR=4.449, 95% : 2.402-8.242), MSM (aOR=1.783, 95% : 1.414-2.248), and infection with CRF07_BC (aOR=3.062, 95% : 1.963-4.777) or CRF55_01B (aOR=5.031, 95% : 3.159-8.014). CONCLUSIONS: Local Guangzhou residents, though accounting for only 24.9% in the PLWH, have a high risk of HIV-1 transmission, to which HIV-1 genotypes and MSM are also important contributors. Molecular network analysis provide important assistance for precision prevention and control of HIV-1 transmission.
Song M, Su H, Xia H
… +3 more, Chen S, Shao L, Jiang Z
Nan Fang Yi Ke Da Xue Xue Bao
· 2026 Jun · PMID 42343847
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OBJECTIVES: To investigate the role of the SREBP-1/SCD1 pathway in mediating the protective effect of (TXYF) against 5-hydroxytryptamine (5-HT)-induced injury in BRL 3A cells. METHODS: Fourteen SD rats were gavaged with...OBJECTIVES: To investigate the role of the SREBP-1/SCD1 pathway in mediating the protective effect of (TXYF) against 5-hydroxytryptamine (5-HT)-induced injury in BRL 3A cells. METHODS: Fourteen SD rats were gavaged with TXYF for 7 consecutive days to prepare TXYF-medicated serum. BRL 3A cells in routine culture were examined for changes in cell viability using CCK-8 assay following treatment with different concentrations of 5-HT. In BRL 3A cells treated with 5-HT and different concentrations of the medicated serum, SOD, MDA, and ROS levels were measured, and mitochondrial membrane potential and cell morphology were evaluated using JC-1 staining and electron microscopy; autophagosomes and LC3B expression were detected with immunofluorescence staining, and the protein expression levels of Cyt-c, caspase-3, Gsk3β, Beclin-1, LC3 I/II, p62, SREBP-1, SCD1, and 5-HTR were analyzed using Western blotting. RESULTS: The optimal 5-HT concentration for modeling was 1.5 mmol/L. In 5-HT-treated cells, treatment with TXYF-medicated serum significantly reduced cellular ROS and MDA levels, increased SOD activities, lowered mitochondrial membrane potential, and alleviated mitochondrial swelling. The cells treated with TXYF-medicated serum also showed decreased expression levels of LC3B, MDC, Beclin-1, LC3 II/LC3 I, Cyt-c, SCD1 and 5-HTR and increased expressions of p62 and SREBP-1 without significant changes in caspase-3 and Gsk3β expressions. CONCLUSIONS: TXYF-medicated serum alleviate oxidative stress and autophagy dysfunction via the SREBP-1/SCD1 pathway to protect BRL 3A cells against 5-HT-induced injury.
Chen Y, You Y, Huang Y
… +3 more, He F, Qiu F, DU Q
Nan Fang Yi Ke Da Xue Xue Bao
· 2026 Jun · PMID 42343846
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OBJECTIVES: To isolate and identify phenolic acid constituents from methanol extract of Thunb. and evaluate their lipid-lowering activity . METHODS: The methanol extract of Thunb. was purified using silica gel, ODS, an...OBJECTIVES: To isolate and identify phenolic acid constituents from methanol extract of Thunb. and evaluate their lipid-lowering activity . METHODS: The methanol extract of Thunb. was purified using silica gel, ODS, and semi-preparative HPLC. The compound structures were determined using physicochemical and spectroscopic analyses, and their hypolipidemic activities were assessed in an AML12 cell model of free fatty acids (FFA)-induced lipid deposition. The active compounds were further assessed for their effects on lipid deposition, reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) of the cell model. RESULTS: A total of 11 phenolic acid compounds were isolated from Thunb., namely dihydrocaffeic acid (), protocatechualdehyde (), chlorogenic acid (), cryptochlorogenic acid (), 1,3-O-dicaffeoylquinic acid (), 2,3-dicarboxy-6,7-hydroxy-l-(3',4'-dihydroxy)-phenyl -1,2-dihydronaphthalene-10-methyl ester (), caffeic acid (), protocatechuic acid (), 3-carboxy-6,7-dihydroxy-1-(3',4'-dihydroxyphenyl)-naphthalene (), p-hydroxybenzoic acid (), and 4-hydroxyphenylacetic acid (). Among them, compounds and were isolated for the first time from the genus , and compound was isolated for the first time from this plant. Compounds and showed lipid-lowering effects in FFA-induced AML12 cells, significantly lowered cellular levels of total cholesterol, triglyceride, alanine aminotransferase, and aspartate aminotransferase, reduced lipid accumulation, and alleviated oxidative stress and mitochondrial function. CONCLUSIONS: Thunb. contains diverse phenolic acids, and among them compounds and show hypolipidemic activities via inhibiting lipid accumulation and improving oxidative stress and mitochondrial function and can potentially serve as lead compounds for treatment of metabolic dysfunction-associated steatotic liver disease.
Yang D, Zhao F, He Y
… +3 more, Zhu H, Liu X, Chen X
Nan Fang Yi Ke Da Xue Xue Bao
· 2026 Jun · PMID 42343845
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OBJECTIVES: To investigate the mechanism that mediates the neuroprotective effects of Maxim (TTM) against post-stroke cognitive impairment (PSCI) in rats. METHODS: Adult SD rats were randomized into Sham operation, PSCI...OBJECTIVES: To investigate the mechanism that mediates the neuroprotective effects of Maxim (TTM) against post-stroke cognitive impairment (PSCI) in rats. METHODS: Adult SD rats were randomized into Sham operation, PSCI model, TTM, rapamycin (an autophagy inducer), 3-methyladenine (an autophagy inhibitor), and TTM+3-MA groups, and rat models of cognitive impairment were established using a modified thread occlusion method. Cognitive function of the rats was assessed using Morris water maze test. Histopathological changes, neuronal apoptosis, dendritic spines, and protein expressions of FAM134B, LC3, ATG5, P62, GRP78, Bax, Bcl-2, IL-10, IL-1β, and TNF-α were evaluated using HE, Nissl, TUNEL, Golgi staining, immunohistochemistry, immunofluorescence staining, and Western blotting. RESULTS: Compared with the sham-operated rats, the rat models of PSCI showed significantly prolonged escape latency, reduced target quadrant time and platform crossings, severe hippocampal damage, increased ATG5 and GRP78 expression, elevated apoptosis, increased IL-1β, TNF-α, Bax, GRP78, and P62 expressions, and decreased IL-10, Bcl-2, and LC3 expressions, with slightly increased FAM134B-LC3 and calnexin-LC3 co-localization. Compared with those in the model group, the rats receiving TTM treatment showed significantly shortened escape latency, increased target quadrant time and platform crossings, increased ATG5 and dendritic spines, decreased GRP78 expression, enhanced FAM134B-LC3 and calnexin-LC3 co-localization, reduced IL-1β, TNF-α, Bax, GRP78, and P62 expressions, and increased FAM134B, ATG5, LC3, IL-10, and Bcl-2 expressions; the rats treated with 3-MA showed the opposite changes. CONCLUSIONS: Excessive ER stress is activated early after stroke, shifting from adaptive to pro-apoptotic signaling, with insufficient ER-phagy flux. TTM modulates ER-phagy, alleviates ERS, reduces neuroinflammation and apoptosis, protects dendritic spines, and improves cognitive function in rats with PSCI.
Wang M, Lu B, Meng H
… +4 more, Zhou S, Mao N, Zhang Y, Lü W
Nan Fang Yi Ke Da Xue Xue Bao
· 2026 Jun · PMID 42343844
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OBJECTIVES: To identify B cell-associated biomarkers in chronic obstructive pulmonary disease (COPD) using bioinformatics and explore their diagnostic and therapeutic potential. METHODS: Based on the GEO database, differ...OBJECTIVES: To identify B cell-associated biomarkers in chronic obstructive pulmonary disease (COPD) using bioinformatics and explore their diagnostic and therapeutic potential. METHODS: Based on the GEO database, differential expression analysis, WGCNA, scRNA-seq, ROC curve analysis, and Mendelian randomization analysis were performed to screen B cell-related biomarkers. Twenty ICR mice were divided equally into control and COPD groups, and COPD model was established using lipopolysaccharide (LPS) combined with cigarette smoke exposure to verify biomarker expression. Cultured murine B lymphoma CH12.LX cells were stimulated with 1 μg/mL LPS and transfected with plasmids overexpressing CRIP1 or NDUFA13 or with a negative control plasmid, and the changes in protein expressions of NDUFB8, MTCO1, ATP5A and ACTB were examined with Western blotting. CCK-8 assay and flow cytometry were used to analyze the viability and apoptosis of murine lung epithelial cells co-cultured with the treated CH12.LX cells, respectively. RESULTS: Two protective factors, namely NDUFA13 (OR=0.2598) and CRIP1 (OR=0.2690; <0.0001), were identified as the key B cell-associated biomarkers in COPD. In the mouse models of COPD, the expressions of NDUFA13 and CRIP1 were significantly downregulated in the lung tissues at both the transcriptional and protein levels. In CH12.LX cells, stimulation with LPS significantly lowered the protein expressions of NDUFA13, CRIP1, NDUFB8, MTCO1 and ATP5A. Overexpression of CRIP1 or NDUFA13 effectively inhibited LPS-induced inflammatory responses and oxidative stress in CH12.LX cells, and promoted the viability and suppressed apoptosis of lung epithelial cells co-cultured with CH12.LX cells. CONCLUSIONS: NDUFA13 and CRIP1 are B cell-associated protective biomarkers in COPD with potential diagnostic values for COPD.
Nan Fang Yi Ke Da Xue Xue Bao
· 2026 Jun · PMID 42343843
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OBJECTIVES: To explore the risk factors for early respiratory failure in patients with acute pancreatitis (AP) and develop an interpretable machine learning model to predict the need for invasive mechanical ventilation (...OBJECTIVES: To explore the risk factors for early respiratory failure in patients with acute pancreatitis (AP) and develop an interpretable machine learning model to predict the need for invasive mechanical ventilation (MV) within 72 h of ICU admission. METHODS: This retrospective cohort study was conducted using data of adult patients with acute pancreatitis from the MIMIC-IV database, excluding those receiving invasive MV at ICU admission. The primary outcome was initiation of invasive MV within 72 h after ICU admission. Multiple machine learning models were developed and internally validated, and the best-performing model was externally validated using the eICU-CRD database. Model interpretability was assessed using SHapley Additive exPlanations (SHAP). RESULTS: A total of 517 patients with acute pancreatitis from the MIMIC-IV database were included, with 361 assigned to the training cohort and 156 to the internal testing cohort; 269 patients from the eICU-CRD database were included as the external validation cohort. The patients who developed early respiratory failure exhibited more severe organ dysfunction at ICU admission. The random forest model achieved an AUC of 0.908 in the training cohort, 0.733 in the internal testing cohort, and 0.681 in the external validation cohort. SHAP analysis identified sequential organ failure assessment (SOFA) score, use of vasoactive agents, and acute kidney injury (AKI) as the most important predictive factors. CONCLUSIONS: The interpretable machine learning model demonstrates moderate predictive performance in both the internal and external validation cohorts and can be used for early risk assessment of invasive MV in patients with acute pancreatitis. The key predictive variables primarily reflect multi-organ dysfunction consistent with the underlying pathophysiological mechanisms of acute pancreatitis.
Jiang Q, Liu T, Wang Z
… +9 more, Jiang S, Wu H, Lin Y, Shiying LU, Chen L, Zhang J, Tang L, Raut RK, Xu Z
Nan Fang Yi Ke Da Xue Xue Bao
· 2026 Jun · PMID 42343842
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OBJECTIVES: To evaluate the efficacy of CD4/TGF-β bispecific antibody in a mouse model of peritoneal metastasis of melanoma. METHODS: For drug safety testing, 20 human CD4 transgenic C57BL/6J mice were randomized into 4...OBJECTIVES: To evaluate the efficacy of CD4/TGF-β bispecific antibody in a mouse model of peritoneal metastasis of melanoma. METHODS: For drug safety testing, 20 human CD4 transgenic C57BL/6J mice were randomized into 4 groups (=5) for intravenous injections of PBS or 2.5, 5, or 10 mg/kg CD4/TGF‑β bispecific antibody, and the changes in general condition, body weight and body temperature were observed. Another 20 transgenic C57BL/6J mice were randomized into two groups to receive intraperitoneal injection of magnetized B16F10-GL melanoma cells expressing green fluorescent protein and luciferase with or without application of a magnet (3 mm in diameter) to the right abdominal skin before cell injection. Three days later, each group was further divided into two groups for treatment with PBS or CD4/TGF-β bispecific antibody (300 μg) twice a week. imaging was performed at different time points to assess fluorescence distribution and intensity. On day 14, the mice were euthanized and tumor burden and dissemination were evaluated by gross observation, histopathological analysis, immunofluorescence staining, and RT-qPCR. RESULTS: Injection of the antibody did not produce any significant adverse effects in the mice. In the tumor-bearing mice, the application of a magnet significantly accelerated tumor development (3.80±1.79 9.20±2.17 days; =0.003) and resulted in precise and consistent tumor formation in the parietal peritoneum. Magnet application did not significantly affect survival of the mice but significantly prolonged the therapeutic window (4.60±1.95 10.00±1.73 days; =0.002). The mice treated with CD4/TGF‑β bispecific antibody had significantly reduced tumor burden irrespective of the inoculation approach, and showed dense encapsulation of the tumor foci by type III collagen, whereas minimal type III collagen deposition and abundant tumor cells were observed in PBS-treated mice. Treatment with the antibody significantly downregulated the expression of melanoma-associated gene MITF, and the reduction was more pronounced in the magnet group. CONCLUSIONS: The CD4/TGF‑β bispecific antibody shows significant antitumor efficacy and good safety in the mouse model of peritoneal metastasis of melanoma.
Guo K, Wang Y, Li Y
… +5 more, Zhang H, Han L, DU R, Ouyang J, Bian H
Nan Fang Yi Ke Da Xue Xue Bao
· 2026 Jun · PMID 42343841
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OBJECTIVES: To investigate the effect of Formula (WHT) for promoting angiogenesis in systemic sclerosis (SSc) dermal microvascular endothelial cells and its possible mechanism. METHODS: Wistar rats were gavaged with 15,...OBJECTIVES: To investigate the effect of Formula (WHT) for promoting angiogenesis in systemic sclerosis (SSc) dermal microvascular endothelial cells and its possible mechanism. METHODS: Wistar rats were gavaged with 15, 30, or 60 g/kg WHT and normal saline for 7 consecutive days to prepare low-, medium-, or high-concentration WHT-medicated sera and blank serum, respectively. Human dermal microvascular endothelial cells (HDMECs) in routine culture were treated with the sera from SSc patients to establish an SSc cell model. The cells were treated with the blank serum, low-, medium-, or high-concentration WHT-medicated sera, or blank serum combined with EGCG (a Sema3A inhibitor). The changes in cell proliferation, migration and angiogenesis were assessed using CCK-8 assay, wound-healing assay and Matrigel tube formation assay, and the mRNA and protein expressions of Sema3A, Nrp1, VEGFA, CD31 and α-SMA were analyzed using qRT-PCR and Western blotting. RESULTS: HDMECs treated with the serum from SSc patients exhibited significantly reduced cell proliferation and migration rates, increased α-SMA, Sema3A and VEGFA protein and mRNA expression levels, decreased CD31 and Nrp1 protein and mRNA expression levels, and suppressed angiogenesis. In SSc serum-induced cells, treatments with low-, medium-, or high-concentration WHT-medicated sera or EGCG all significantly improved cell survival and migration rates, reduced α-SMA, Sema3A and VEGFA protein and mRNA expression levels, enhanced CD31 and Nrp1 protein and mRNA expressions, and promoted angiogenesis of the cells. CONCLUSIONS: WHT promotes angiogenesis of SSc sera-induced HDMECs by modulating the Sema3A/Nrp1 signaling pathway.
Nan Fang Yi Ke Da Xue Xue Bao
· 2026 Jun · PMID 42343840
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OBJECTIVES: To investigate the mechanism by which chronic iron overload induces diminished ovarian reserve (DOR) in mice. METHODS: Forty female C57BL/6J mice with normal estrous cycles were randomly divided into 4 groups...OBJECTIVES: To investigate the mechanism by which chronic iron overload induces diminished ovarian reserve (DOR) in mice. METHODS: Forty female C57BL/6J mice with normal estrous cycles were randomly divided into 4 groups (=10) for intraperitoneal injections of normal saline or iron dextran at 0.1, 0.5 or 1.0 g/kg once a week for 8 consecutive weeks. The changes in body weight and food intake of the mice were monitored weekly. Vaginal smears were used to assess estrous cycle changes of the mice, and wet weights of bilateral ovaries and uterus were recorded. Ovarian histopathology was evaluated by HE staining, iron deposition was detected by Prussian blue staining; serum levels of sex hormones (FSH, LH, E, and AMH) and the levels of MDA and SOD in the ovarian tissue were determined, and reactive oxygen species (ROS) production was assessed on frozen sections of the ovarian tissue. Mitochondrial ultrastructural changes in the ovaries of the mice were observed with transmission electron microscopy, and ovarian expression levels of , , , , and mRNAs and Tf, Tfr1, Ft, Fth1, Ftl and Gpx4 protein were detected. RESULTS: The mice receiving injections of 0.5 and 1.0 g/kg iron dextran exhibited disrupted estrous cycles, increased atretic follicles, decreased ovarian index, and increased uterine index with reduced AMH and E₂ levels and increased FSH and LH levels. The injections caused significant iron accumulation, oxidative stress, and obvious mitochondrial damage in the ovarian tissues, resulting also in downregulation of Tf, Tfr1, Gpx4, Gpx1 and Cat and upregulation of Ft, Ftl and Fth1 expressions. CONCLUSIONS: Iron dextran at 0.5 and 1.0 g/kg can induce chronic, dose-dependent iron overload in mice, which causes systemic iron metabolism disorders and disrupted iron homeostasis to trigger oxidative stress damage and endocrine dysfunction and ultimately induce DOR.
Wang P, Zhang K, Wang H
… +6 more, Yang L, Liu Y, Cao J, Li H, Mi W, Lou J
Nan Fang Yi Ke Da Xue Xue Bao
· 2026 Jun · PMID 42343839
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OBJECTIVES: To investigate whether preoperative cardiology consultation reduces the incidence of major adverse cardiac events (MACE) in patients undergoing non-cardiac surgeries. METHODS: This cohort study was conducted...OBJECTIVES: To investigate whether preoperative cardiology consultation reduces the incidence of major adverse cardiac events (MACE) in patients undergoing non-cardiac surgeries. METHODS: This cohort study was conducted among 7019 elderly patients (above 65 years) with abnormal ECGs undergoing non-cardiac surgeries. The main outcome was MACE occurrence within 30 days post-surgery. The patients were divided into model development and validation cohorts in a 7:3 ratio, and each cohort was categorized into two subgroups with high-risk and low-risk abnormal ECG. MACE prediction models were constructed for the subgroups, and their predictive power was evaluated using ROC curves; the value of preoperative cardiology consultation for reducing MACE was assessed using decision curve analysis. RESULTS: Among the 4914 patients in the model development cohort, 61 of the 3010 patients with low-risk abnormal ECGs experienced MACE (2.0%), as compared with 59 out of 1904 patients (3.1%) in the high-risk group. The predictive model for MACE for the low-risk group contained 6 risk factors (AUC=0.772), and that for the high-risk group contained 5 risk factors (AUC=0.769). In patients with low-risk abnormal ECG, undergoing cardiovascular specialist consultation did not show significant benefits (the survival rate for predicting MACE was 0.02). However, in patients with high-risk abnormal ECG and those with low-risk abnormal ECG but having specific risk factors, undergoing cardiovascular specialist consultation showed significant benefits with survival rates for predicting MACE of 0.3 and 0.229, respectively. CONCLUSIONS: For patients with high-risk abnormal ECG and those with low-risk abnormal ECG and specific risk factors, preoperative cardiology consultation may help to reduce the occurrence of MACE following non-cardiac surgeries, but for patients with simple low-risk abnormal ECG cases without risk factors, preoperative cardiology consultation can be omitted, which does not affect the incidence of MACE but can improve medical efficiency.
Nan Fang Yi Ke Da Xue Xue Bao
· 2026 Jun · PMID 42343838
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OBJECTIVES: To investigate the role of ZEB2 in lipid metabolic reprogramming of glioblastoma and its mechanism for promoting glioblastoma progression. METHODS: Mouse models bearing orthotopic intracranial xenografts deri...OBJECTIVES: To investigate the role of ZEB2 in lipid metabolic reprogramming of glioblastoma and its mechanism for promoting glioblastoma progression. METHODS: Mouse models bearing orthotopic intracranial xenografts derived from LN-229 and GBM007 cells with stable ZEB2 knockdown were used to assess tumor growth and mouse survival.. Lipid droplet accumulation, lipid composition, and membrane fluidity in the cells with ZEB2 knockdown were examined using Nile Red staining, transmission electron microscopy, untargeted lipidomics, and fluorescence recovery after photobleaching (FRAP). The candidate mediators were screened by integrating RNA sequencing, fatty acid synthase (FASN) immunoprecipitation-mass spectrometry, and BioGRID interaction data. Promoter luciferase assays, ChIP-qPCR, promoter mutagenesis, co-immunoprecipitation, protein degradation pathway inhibition, and ubiquitination assays were performed to investigate the regulatory role of the ZEB2-CYLD-FASN axis. RESULTS: ZEB2 knockdown significantly suppressed intracranial glioblastoma growth and prolonged mouse survival. Glioblastoma cells with ZEB2 silencing showed reduced lipid droplet accumulation, decreased saturated fatty acid-associated storage lipids, increased phospholipid species containing polyunsaturated fatty acyl chains, and enhanced membrane fluidity. Mechanistically, ZEB2 knockdown reduced FASN protein abundance, whereas FASN restoration reversed lipid droplet reduction induced by ZEB2 silencing. Multi-omics screening identified CYLD as a key intermediate. ZEB2 was capable of directly binding to and activating the CYLD promoter. CYLD knockdown decreased FASN protein levels, whereas CYLD restoration recovered FASN abundance and lipid droplet formation. CYLD was co-localized and interacted with FASN. MG132 partially restored FASN abundance under ZEB2 knockdown, and CYLD overexpression reduced FASN ubiquitination. CONCLUSIONS: ZEB2 promotes glioblastoma lipid metabolic reprogramming and tumor progression by transcriptionally activating CYLD, which maintains FASN protein stability at least in part through ubiquitination-associated regulation.
Nan Fang Yi Ke Da Xue Xue Bao
· 2026 Jun · PMID 42343837
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OBJECTIVES: To construct AS1411 aptamer-modified mesoporous polydopamine (MPDA) nanoparticles co-loaded with doxorubicin (DOX) and catalase (AS1411-D/C-MPDA nanoparticles) targeting the tumor microenvironment and evaluat...OBJECTIVES: To construct AS1411 aptamer-modified mesoporous polydopamine (MPDA) nanoparticles co-loaded with doxorubicin (DOX) and catalase (AS1411-D/C-MPDA nanoparticles) targeting the tumor microenvironment and evaluate their efficacy in synergy with ultrasound for inhibiting Lewis lung carcinoma (LLC) cells. METHODS: AS1411-D/C-MPDA nanoparticles were synthesized using a one-step assembly method, and their physicochemical properties were characterized. Cultured LLC cells were treated with free DOX, DOX-loaded MPDA nanoparticles or AS1411-D/C-MPDA nanoparticles with or without ultrasound exposures (frequency 1.0 MHz and intensity 1.0 W/cm²) for 3 min. The changes in viability, apoptosis, and migration and invasion abilities of the cells were assessed using CCK-8 assay, flow cytometry (Annexin V-FITC/PI staining), wound healing assay, and Transwell assay, respectively. RESULTS: The prepared AS1411-D/C-MPDA nanomaterials showed a uniform spherical morphology, a mean particle size of 183.36±15.99 nm, and DOX and catalase encapsulation efficiencies of (91.17±0.08)% and (29.59±0.2)%, respectively. The nanoparticles demonstrated good pH responsiveness to enable disintegration for promoting drug release, with a cumulative DOX release rate of (81.25±1.61)%. The nanoparticles possessed strong oxygen-generating capacity to alleviate cell hypoxia. AS1411-modified nanoparticles showed significantly enhanced cellular uptake by LLC cells. Compared with free DOX and DOX-MPDA nanoparticles combined with ultrasound, AS1411-D/C-MPDA in synergy with ultrasound induced higher levels of ROS in LLC cells, resulted in a higher cell apoptosis rate, and more efficiently reduced cell viability and suppressed cell migration and invasion. CONCLUSIONS: AS1411-D/C-MPDA nanoparticles combined with ultrasound allow targeted delivery of anticancer drugs and represent a promising strategy for synergistic treatment of lung cancer by integrating physical acoustics, pharmaceutical chemistry, and tumor microenvironment regulation.
Nan Fang Yi Ke Da Xue Xue Bao
· 2026 Jun · PMID 42343836
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OBJECTIVES: To investigate the role of lactate in myocardial ischemia-reperfusion (MIR)-induced gastric mucosal injury. METHODS: Thirty C57BL/6J mice were randomized into sham-operated group, MIR (45 min ischemia and 2 h...OBJECTIVES: To investigate the role of lactate in myocardial ischemia-reperfusion (MIR)-induced gastric mucosal injury. METHODS: Thirty C57BL/6J mice were randomized into sham-operated group, MIR (45 min ischemia and 2 h reperfusion) group, and MIR+LDHAI group, and gastric mucosal injury was assessed using macroscopic scoring and HE staining; serum lactate and cTnT levels were measured using ELISA. Metabolomics analysis was conducted to identify the differential serum metabolites between the sham-operated and MIR mice. In the cell experiment, human gastric mucosal cells (GES-1) were indirectly co-cultured with THP-1 cell-derived macrophages polarized to the M1 phenotype by lactate and/or lipopolysaccharide (LPS) stimulation. In both the gastric mucosa tissues of the mice and the co-cultured GES-1 cells, the protein expression levels of CD68, iNOS, Arg-1, COX-1, and COX-2 were detected using Western blotting and immunofluo-rescence staining. RESULTS: Compared to sham operation, MIR induced concurrent injury in both the heart and stomach of the mice and caused elevation of iNOS protein levels and reduction of Arg-1 protein expression in the gastric mucosa, where increased overlapping fluorescent areas were detected after MIR using fluorescent double-labeling for CD68 and iNOS. Serum metabolomics analysis revealed a significant increase in circulating lactate levels after MIR. In GES-1 cells, indirect co-culture with M1 macrophages induced obvious cell injury, decreased COX-1 expression, and increased cellular COX-2 protein expression. Western blotting and immunofluorescence staining confirmed that 15 mmol/L lactate significantly increased iNOS and decreased Arg-1 expression in THP-1-derived macrophages. Indirect co-culture of GES-1 cells with M1 macrophages induced by lactate or LPS resulted in obvious GES-1 cell injury. In the mouse models of MIR, inhibition of lactic acid production effectively alleviated MIR-induced gastric mucosal injury. CONCLUSIONS: Lactate-induced M1 macrophage polarization mediates MIR-related gastric mucosal injury in mice via the heart-gastric axis, an effect reversible by LDHA inhibition.
Wang Z, Wu J, Wang H
… +3 more, Xu Y, Jiang C, Zhou L
Nan Fang Yi Ke Da Xue Xue Bao
· 2026 Jun · PMID 42343835
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OBJECTIVES: To investigate the association between the red blood cell distribution width to hematocrit (RDW/HCT) ratio and 28-day all-cause mortality in patients with sepsis. METHODS: A retrospective cohort study was con...OBJECTIVES: To investigate the association between the red blood cell distribution width to hematocrit (RDW/HCT) ratio and 28-day all-cause mortality in patients with sepsis. METHODS: A retrospective cohort study was conducted using the MIMIC-IV database (27 335 adult patients), and the eICU-CRD database was used for external validation (17 406 adult patients). The patients were grouped by RDW/HCT ratio quartiles. The primary outcome was 28-day all-cause mortality. Kaplan-Meier survival curves were used to assess the survival rates. Multivariable Cox regression and restricted cubic spline (RCS) analyses were performed to examine the association between RDW/HCT ratio and patient mortality. Subgroup analyses were conducted to assess the robustness of the findings. RESULTS: The 28-day mortality rates were 19.3% in the MIMIC-IV cohort and 16.0% in the eICU-CRD cohort. In the MIMIC-IV cohort, Kaplan-Meier analysis showed that a higher RDW/HCT ratio was associated with an increased risk of 28-day mortality in septic patients (log-rank <0.0001). Multivariable Cox regression analysis suggested that an elevated RDW/HCT ratio was an independent risk factor for 28-day mortality in septic patients (HR=1.89, 95% : 1.52-2.36, <0.001). RCS analysis showed a non-linear, U-shaped relationship between the RDW/HCT ratio and 28-day mortality of septic patients. No significant interactions were observed in subgroup analyses. The trends in the eICU-CRD validation cohort were consistent with those observed in the MIMIC-IV cohort. n Elevation of the RDW/HCT ratio is associated with an increased 28-day all-cause mortality rate in patients with sepsis.
Yin L, Zhang Y, Zhang K
… +6 more, Qiao T, Zhang L, Huang J, Li J, Hu J, Geng Z
Nan Fang Yi Ke Da Xue Xue Bao
· 2026 Jun · PMID 42343834
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OBJECTIVES: To investigate the protective effect of 1,3-dicaffeoylquinic acid (1,3-DA) against dextran sulfate sodium (DSS)-induced colitis in mice and its molecular mechanism. METHODS: Fifty C57BL/6 mice were randomly d...OBJECTIVES: To investigate the protective effect of 1,3-dicaffeoylquinic acid (1,3-DA) against dextran sulfate sodium (DSS)-induced colitis in mice and its molecular mechanism. METHODS: Fifty C57BL/6 mice were randomly divided into normal control group, DSS model group, 1,3-DA treatment group, PI3K inhibitor (LY294002), and 5-aminosalicylic acid (5-ASA; positive control) group. Except for those in the control group, the mice were given DSS to induce colitis and treated with daily intraperitoneal injections the indicated agents during modeling for 7 consecutive days. Colonic pathological phenotypes, inflammation, oxidative stress, and expressions of tight junction proteins and PI3K/Akt pathway proteins in the colon tissues of the mice were detected. In cultured intestinal epithelial NCM460 cells with H₂O₂-induced oxidative stress, the effects of 1,3-DA and 1,3-DA plus 740Y-P (a PI3K activator) were examined on intracellular oxidative stress and expressions of tight junction proteins. RESULTS: Treatment of the mice with 1,3-DA significantly alleviated DSS-induced body weight loss, colon shortening, elevation of disease activity index and mucosal injury, downregulated interferon‑γ and myeloperoxidase, upregulated superoxide dismutase, catalase and glutathione peroxidase, reduced malondialdehyde, increased zonula occludens-1 and claudin-1, and inhibited overexpressions of phosphorylated PI3K (p-PI3K) and phosphorylated Akt (p-Akt). In NCM460 cells, treatment with 1,3-DA significantly reduced H₂O₂-induced reactive oxygen species accumulation, increased zonula occludens-1 and claudin-1 expressions, and lowered p-PI3K and p-Akt expression. The protective effects of 1,3-DA was obviously attenuated by treatment with 740Y-P. CONCLUSIONS: 1,3-DA ameliorates DSS-induced colitis in mice and H₂O₂-mediated intestinal epithelial injury by inhibiting inflammation and oxidative stress and promoting repair of intestinal barrier function, which is closely related to inhibition of excessive PI3K/Akt pathway activation.