Nan Fang Yi Ke Da Xue Xue Bao = Journal Of Southern Medical University[JOURNAL]
Sun
200 papers
[Targeted inhibition of miR-503 upregulates Apelin expression to alleviate myocardial infarction in mice].
Li J, He Y, Bi F … +8 more , Chen J, Fan Z, Zhang Y, Chen E, Xiao H, Wu Y, Tian H, Zhou Y
Nan Fang Yi Ke Da Xue Xue Bao · 2026 Jun · PMID 42343833 · Full text
OBJECTIVES: To investigate the effect of inhibiting miR-503 on myocardial infarction (MI) and clarify its upstream regulatory factors and downstream effector pathways to identify potential therapeutic targets for MI. MET...
OBJECTIVES: To investigate the effect of inhibiting miR-503 on myocardial infarction (MI) and clarify its upstream regulatory factors and downstream effector pathways to identify potential therapeutic targets for MI. METHODS: Mouse models of MI established by ligation of the left anterior descending coronary artery were treated with intravenous injections of normal saline, antagomir-503 or antagomiR-NC (=5). Cardiac function and infarct size of the mice were evaluated by echocardiography and TTC staining, respectively. Primary neonatal rat cardiomyocytes with hypoxic exposure were treated with AMO-503 or its negative control, and the changes in miR-503 expression was detected by qRT-PCR. Cell viability, injury, apoptosis, mitochondrial membrane potential, and ultrastructure were assessed using MTT assay, LDH release assay, TUNEL staining, JC-1 staining, and transmission electron microscopy, respectively. Western blotting was performed to detect the changes in apoptosis-related proteins and the key targets. RESULTS: MiR-503 expression was significantly upregulated in both MI mouse hearts and hypoxic cardiomyocytes. In MI mouse models, antagomir-503 significantly improved cardiac function, reduced infarct size, downregulated Bax and cleaved caspase-3 expressions, and upregulated Apelin expression. In hypoxic neonatal rat cardiomyocytes, treatment with AMO-503 significantly enhanced cell viability, decreased cell apoptosis rate, and restored mitochondrial membrane potential. Mechanistically, the long non-coding RNA AK134630 could bind to and negatively regulate miR-503, and inhibition of miR-503 effectively relieved the inhibitory effect of RNA AK134630 on the downstream target gene Apelin. CONCLUSIONS: Inhibition of miR-503 alleviates MI injury in mice by upregulating Apelin expression to inhibit cardiomyocyte apoptosis and protect mitochondrial function, and AK134630 participates in this regulatory mechanism as an upstream ceRNA of miR-503.
[Effect of intraoperative dexmedetomidine on postoperative sleep disturbance in elderly surgical patients: a prospective multicenter cohort study].
Meng B, Liu C, Liao G … +9 more , Zhang K, Yang M, Gu J, Lou J, Liu Y, Fu Q, Cao J, Mi W, Li H
Nan Fang Yi Ke Da Xue Xue Bao · 2026 Jun · PMID 42343832 · Full text
OBJECTIVES: To investigate the association between intraoperative dexmedetomidine administration and postoperative sleep disturbance in elderly patients undergoing noncardiac surgeries. METHODS: This prospective observat...
OBJECTIVES: To investigate the association between intraoperative dexmedetomidine administration and postoperative sleep disturbance in elderly patients undergoing noncardiac surgeries. METHODS: This prospective observational study included patients aged ≥65 years undergoing noncardiac surgeries between April, 2020 and April, 2022 in multiple hospitals. The primary outcome was the incidence of postoperative sleep disturbance within 3 days after surgery, assessed using the Sleep Quality-Numeric Rating Scale. The secondary outcomes included the incidences of sleep disturbance on the night of surgery and two subsequent nights, postoperative severe pain, postoperative delirium, acute kidney injury, stroke and pulmonary infection. Univariate and multivariate logistic regression analyses were conducted to explore the relationship between dexmedetomidine and postoperative sleep disturbance. Propensity score matching was used to balance the baseline characteristics, and subgroup analyses were performed to explore the association between dexmedetomidine and postoperative sleep disturbance. RESULTS: Among the 5245 patients, 1352 (25.78%) developed postoperative sleep disturbance within 3 days after surgery. The incidence of postoperative sleep disturbance was significantly lower in dexmedetomidine group than in the non-dexmedetomidine group (unadjusted: 21.0% 27.9%, <0.001; PSM: 20.7% 25.4%, <0.001). Dexmedetomidine was significantly associated with a reduced risk of postoperative sleep disturbance (unadjusted: OR=0.69, 95% : 0.60-0.79, <0.001; Model I: OR=0.76, 95% : 0.66-0.87, <0.001; Model II: OR=0.75, 95% : 0.65-0.87, <0.001; PSM: OR=0.77, 95% : 0.65-0.91, <0.001), and the association remained significant in subgroup analyses for gender, ASA classification, surgery duration, and surgical types). The incidences of severe postoperative pain, postoperative delirium and pulmonary infection were all significantly lower in dexmedetomidine group. CONCLUSIONS: Intraoperative dexmedetomidine administration is associated with reduced postoperative sleep disturbance in elderly patients undergoing noncardiac surgery and lowers the incidences of severe postoperative pain, postoperative delirium and pulmonary infections.
[ Granules alleviate renal fibrosis in mice with unilateral ureteral obstruction by regulating Akt3-mediated M1 macrophage polarization].
Wang W, Gao Y, Hong X … +5 more , Chen Y, Cheng M, Zhang L, Dai R, Wang Y
Nan Fang Yi Ke Da Xue Xue Bao · 2026 Jun · PMID 42343831 · Full text
OBJECTIVES: To clarify whether Granules (QSG) inhibits renal fibrosis by regulating Akt3-mediated macrophage polarization. METHODS: Adult C57BL/6 mice were randomized into Sham group, unilateral ureteral obstruction (UU...
OBJECTIVES: To clarify whether Granules (QSG) inhibits renal fibrosis by regulating Akt3-mediated macrophage polarization. METHODS: Adult C57BL/6 mice were randomized into Sham group, unilateral ureteral obstruction (UUO) model group, and UUO with QSG treatment group (=6) for treatment with daily gavage of distilled water or QSG (4.0 g/kg) as indicated for 2 weeks. In AAV9 experiments, the mice received intrarenal injections of AAV9-shRNA(Akt3)-GFP for Akt3 knockdown or AAV9-shRNA-GFP (negative control) 2 weeks before sham operation or UUO modeling. After the treatments, the mice were examined for renal fibrosis, renal function, and macrophage polarization using HE staining, Masson staining, ELISA, Western blotting, RT-qPCR, immunohistochemistry, immunofluorescence staining, and flow cytometry. In the cell experiment, TGF‑β1-induced HK-2 cells were co-cultured with THP-1-derived macrophages, and the effects of QSG-medicated rat serum on cell viability, proliferation, and macrophage polarization were evaluated using CCK-8 and EdU assays, Western blotting and flow cytometry. RESULTS: Compared with the sham-operated mice, the UUO mice showed impaired renal function, renal tubular injury, collagen deposition, upregulated expressions of IL-6 and TNF-α mRNA and α-SMA protein, and downregulated E-cad protein expression, which were significantly improved by QSG treatment. In AAV9 experiments, the UUO mice with control virus injection showed obvious renal fibrosis and increased M1 macrophages, while AAV9-shRNA(Akt3)‑GFP injection significantly alleviated renal fibrosis and inhibited M1 macrophage polarization without affecting M2 macrophages. In the co-cultured cells, treatment with QSG-medicated serum significantly reversed TGF-β1-induced reduction of HK-2 cell viability and proliferation, upregulated Akt3 and α‑SMA expressions, downregulated E-cad expression, and inhibited M0-to-M1 polarization of THP-1 cells induced by TGF‑β1-treated HK-2 cells. CONCLUSIONS: QSG alleviates renal fibrosis in UUO mice by inhibiting Akt3-mediated M1 macrophage polarization.
pills alleviate myocardial ischemia-reperfusion injury by enhancing mitochondrial function activating the ERK signaling pathway.
Wang Y, Song Z, Guo L … +3 more , Xiao Y, Chen R, Wang Y
Nan Fang Yi Ke Da Xue Xue Bao · 2026 Jun · PMID 42343830 · Full text
: To explore the mechanism of pills (TMYX) for improving myocardial ischemia-reperfusion injury (MIRI) in rats. : In a SD rat model of MIRI, the therapeutic effects of TMYX were evaluated by cardiac echography, measurem...
: To explore the mechanism of pills (TMYX) for improving myocardial ischemia-reperfusion injury (MIRI) in rats. : In a SD rat model of MIRI, the therapeutic effects of TMYX were evaluated by cardiac echography, measurement of myocardial infarction area, and examination of myocardial pathology, myocardial enzymes, and serum levels of inflammatory cytokines. In cultured H9c2 cells, the protective effects of aqueous extract of TMYX in the presence or absence of an ERK inhibitor against hypoxia/reoxygenation (H/R) injury and on mitochondrial function were evaluated by assessing cell viability, apoptosis, reactive oxygen species (ROS) levels, cytoplasmic and mitochondrial Ca²⁺ concentrations, mitochondrial membrane potential, mitochondrial permeability transition pore (mPTP) opening, and mitochondrial respiration. The mitochondria-related indicators were measured to validate the role of the ERK signaling pathway in mediating the alleviating effect of TMYX on mitochondrial function in H9c2 cells with H/R injury. : In rat models of MIRI, TMYX significantly improved cardiac function, alleviated myocardial injury, and reduced inflammatory factor levels, oxidative stress, and myocardial infarction area. In H9c2 cells with H/R injury, TMYX treatment obviously enhanced H9c2 cell viability, increased cellular ATP and ATPase levels and mitochondrial membrane potential, and reduced cell apoptosis rate, ROS level, and mPTP opening. The application of the ERK inhibitor significantly attenuated the protective effect of TMYX on mitochondrial function of H9c2 cells with H/R injury. : TMYX alleviate MIRI in rats by promoting mitochondrial function activating the ERK signaling pathway.
[Guangdong consensus on integrated Chinese and Western medicine management of prolonged disorders of consciousness].
Neurocritical Care Committee of Guangdong Provincial Association of Chinese Medicine
Nan Fang Yi Ke Da Xue Xue Bao · 2026 May · PMID 42198981 · Full text
Severe traumatic brain injury often results in disorders of consciousness. After acute-phase management, some patients gradually regain consciousness, yet many progress to prolonged disorders of consciousness (pDoC). In...
Severe traumatic brain injury often results in disorders of consciousness. After acute-phase management, some patients gradually regain consciousness, yet many progress to prolonged disorders of consciousness (pDoC). In this stage, intracranial pathology stabilizes, and precise assessment of brain function combined with consciousness-promoting therapy becomes the cornerstone of comprehensive care. Currently, the Western medical treatments of pDoC primarily involves pharmacological and neuromodulation therapies, but their efficacy remains controversial and lacks support from high-quality evidence. In traditional Chinese medicine (TCM), pDoC is categorized under "", with abundant documentation in classical texts. Modern research has also explored the therapeutic effects and mechanisms of TCM for this condition and demonstrated its great potential in improving brain functional connectivity and promoting recovery of consciousness. However, the efficacy and mechanisms of TCM interventions still lack robust support from high-quality research evidence. Although integrated Chinese and Western medicine is widely employed for pDoC, no evidence-based guidelines or consensus specific to the condition are currently available. To improve the clinical proficiency across Guangdong Province and standardize the integrative management of pDoC, the consensus working group convened 35 leading Chinese and Western medicine experts in neurology, neurosurgery, and rehabilitation. Based on the latest domestic and international evidence, they developed recommendations on diagnosis, evaluation, integrated treatment strategies, complication management, healthcare system development, and ethical considerations, aiming to provide an authoritative reference for clinical decision-making in pDoC management.
[A vessel-enhanced consistency-preserving diffusion model for 3T-to-7T susceptibility weighted image generation].
Wang T, Duan C, Lou X … +1 more , Feng Q
Nan Fang Yi Ke Da Xue Xue Bao · 2026 May · PMID 42198980 · Full text
OBJECTIVES: To develop a method for generating 7T susceptibility weighted image (SWI) from 3T SWI data for more accurate vascular structure reconstruction. METHODS: We propose a vessel-enhanced consistency-preserving dif...
OBJECTIVES: To develop a method for generating 7T susceptibility weighted image (SWI) from 3T SWI data for more accurate vascular structure reconstruction. METHODS: We propose a vessel-enhanced consistency-preserving diffusion model for synthesizing 7T SWI. This method first utilizes a pre-trained vessel segmentation network to extract vessel maps from both 3T and 7T SWI as vascular priors. The vessel maps from 7T SWI are employed to construct an intra-slice vessel-enhanced loss and reinforce the reconstructed fine vascular structures. An inter-slice feature fusion module and a vessel-aware consistency constraint are integrated into the diffusion model to enhance the spatial coherence of the generated results. The feature fusion module integrates contextual features from adjacent slices a cross-attention mechanism, enabling deep information interaction across multiple slices. The vessel-aware consistency constraint employs an inter-slice vessel-aware consistency-preserving loss to impose constraints on overlapping regions of the sliding windows, thereby enhancing generation coherence across slices. RESULTS: The experiment conducted on 209 paired 3T-7T SWI datasets showed that, compared to the suboptimal method EDM, the proposed method increased the PSNR by 1.39 dB, improved the SSIM by 2.28%, enhanced the skeleton coverage similarity (SCS) by 6.57%, and reduced MAE and LPIPS by 15.84% and 17.07%, respectively. Qualitative analysis further validated the model's superiority in generating vascular details, including accurate restoration of major venous structures and clear delineation of low-contrast microvessels, with natural continuous vascular branches. Ablation studies confirmed the effectiveness of each individual module and their contribution to the performance gains. CONCLUSIONS: The proposed method can effectively synthesize 7T SWI images with clear vascular details from 3T SWI to facilitate clinical and scientific analyses while balancing computational resource requirements and image reconstruction quality.
[Hierarchical attention-driven multiple instance learning for clear cell renal cell carcinoma grading and staging in digital pathology].
Xu J, Mao Y, Zhang Y
Nan Fang Yi Ke Da Xue Xue Bao · 2026 May · PMID 42198979 · Full text
OBJECTIVES: To develop a hierarchical attention-driven multiple instance learning (HA-MIL) framework for precise grading and staging of clear cell renal cell carcinoma (ccRCC). METHODS: Whole-slide images (WSIs) and the...
OBJECTIVES: To develop a hierarchical attention-driven multiple instance learning (HA-MIL) framework for precise grading and staging of clear cell renal cell carcinoma (ccRCC). METHODS: Whole-slide images (WSIs) and the corresponding clinicopathological labels were obtained from 504 patients from the TCGA-KIRC database. The proposed HA-MIL framework processes WSIs by segmenting them into patches, leverages a hierarchical attention mechanism to discern the significance of instances across different levels and incorporates a dynamic gated fusion module to refine feature aggregation. This approach mitigates the dependency on subjective evaluations by pathologists. RESULTS: Experimental results showed that HA-MIL achieved an accuracy of (87.35±0.72)%, an AUC of 0.95, and an F1-score of (86.41±0.63)% in the staging task. For the grading task, the model attained an accuracy of (85.82±0.60)%, an AUC of 0.93, and an F1-score of (86.00±0.65)%. HA-MIL demonstrated significantly higher accuracy and robustness compared to the baseline methods including SVM, DSMIL, and ABMIL. Ablation studies confirmed the contribution of the hierarchical attention mechanism, which improved the accuracy and F1-score by 3.2% and 2.2%, respectively, outperforming the conventional attention mechanisms. CONCLUSIONS: The HA-MIL framework exhibits superior performance for grading and staging of ccRCC, thus offering a novel, intelligent method for pathological image analysis of ccRCC in the clinical setting.
[Dual-wavelength photoacoustic microscopy for evaluation of microcirculatory dysfunction and spatial heterogeneity in mice with liver fibrosis].
Xia Q, Qiu Y, Li H … +1 more , Nie L
Nan Fang Yi Ke Da Xue Xue Bao · 2026 May · PMID 42198978 · Full text
OBJECTIVES: To investigate microcirculatory dysfunction and spatial heterogeneity in mice with liver fibrosis using dual-wavelength high-resolution photoacoustic microscopy (PAM). METHODS: In a male C57BL/6 mouse model o...
OBJECTIVES: To investigate microcirculatory dysfunction and spatial heterogeneity in mice with liver fibrosis using dual-wavelength high-resolution photoacoustic microscopy (PAM). METHODS: In a male C57BL/6 mouse model of CCl₄-induced liver fibrosis, multiparametric imaging of intrahepatic microcirculation was performed using dual-wavelength PAM. The acquired images were used for reconstruction of blood oxygen saturation (sO) distribution maps based on PAM signals and using a spectral unmixing algorithm. The portal area and central vein region within the hepatic lobule were defined as the main regions of interest, and Evans Blue dynamic extravasation analysis was used to assess vascular permeability and spatial heterogeneity of fibrosis progression. Intrahepatic microvascular blood flow velocity was measured using the Doppler bandwidth broadening method, and the local metabolic rate of oxygen (MRO₂) was calculated based on sO parameters. RESULTS: Compared with normal mice, the mice with liver fibrosis exhibited disorganized intrahepatic microvascular network architecture, focal rarefaction, and impaired branching structures with significantly decreased intrahepatic microvascular sO [(93.62±2.44)% (85.53±3.37)%, <0.05). Evans Blue dynamic tracing showed increased extravasation in the liver fibrosis group, and tracer diffusion kinetics differed significantly between the portal area and central vein region within the hepatic lobule, indicating marked spatial heterogeneity. Microvascular blood flow velocity was significantly lower in liver fibrosis group than in the normal control group (3.43±0.32 4.16±0.25 mm/s; <0.05). The local MRO₂ showed a decreasing trend in the liver fibrosis group compared with the normal control group (0.40±0.026 mL·100 g·min 0.35±0.048 mL·100 g·min). CONCLUSIONS: Multiparametric imaging based on PAM enables systematic and multidimensional assessment of microcirculatory structural and functional alterations in mice during liver fibrosis progression, highlighting significant reductions of intrahepatic microvascular sO and blood flow velocity. This approach combined with spatial heterogeneity analysis provides important imaging evidence for staging assessment, mechanistic study, and therapeutic efficacy evaluation for liver fibrosis.
[Melatonin alleviates cardiomyocyte necroptosis in diabetic mice by inhibiting the STING signaling pathway].
Ma D, Cao S, Jiang Y … +4 more , Peng Y, He A, Luo M, Luo S
Nan Fang Yi Ke Da Xue Xue Bao · 2026 May · PMID 42198977 · Full text
OBJECTIVES: To investigate the protective effect of melatonin against diabetic cardiomyopathy (DCM) and whether melatonin regulates cardiomyocyte necroptosis and inflammatory response through the stimulator of interferon...
OBJECTIVES: To investigate the protective effect of melatonin against diabetic cardiomyopathy (DCM) and whether melatonin regulates cardiomyocyte necroptosis and inflammatory response through the stimulator of interferon genes (STING) signaling pathway. METHODS: C57 mouse models of DCM induced by streptozotocin (STZ) injection were given an intraperitoneal injection of saline or melatonin (=6), and 24 h later blood and myocardial samples were collected from the mice for analysis. A cell model of DCM was established in HL-1 cells by high glucose treatment (33 mmol/L). Pathological changes in myocardial tissue of the mice were observed using HE staining. Immunofluorescence staining and Western blotting were used to detect the key necroptosis proteins, and the pro-inflammatory factors including IL-1β, IL-6, and TNF-α were detected with Western blotting and ELISA to evaluate cell death and inflammation. The expression levels of the proteins associated with STING pathway activation (P-IRF3 and P-P65) were detected using immunohistochemistry and Western blotting. RESULTS: In the diabetic mice and cell models of DCM, the STING signaling pathway was activated with significantly increased protein expressions of STING and P-IRF3. The myocardial tissues of DCM mice showed increased inflammatory infiltration with upregulated serum and myocardial levels of IL-1β, IL-6, and TNF-α and increased levels of necroptosis-related proteins P-MLKL, P-RIPK1, and P-RIPK3. Treatment with melatonin significantly inhibited the activation of the STING signaling pathway and reduced the expression levels of inflammatory factors and necroptosis-related proteins, and the use of the STING agonist DMXAA significantly attenuated the protective effect of melatonin. CONCLUSIONS: Melatonin effectively alleviates cardiomyocyte necroptosis and inflammatory response in DCM by inhibiting the STING signaling pathway.
[Q-switched Nd:YAG 1064 nm laser combined with topical metformin lotion for treatment of chloasma in mice].
Jiang L, Zhao M, Liu X … +2 more , Yang H, Mou Y
Nan Fang Yi Ke Da Xue Xue Bao · 2026 May · PMID 42198976 · Full text
OBJECTIVES: To evaluate the efficacy and safety of Q-switched Nd:YAG 1064 nm laser and topical 30% metformin lotion for treatment of chloasma in mice and explore the possible therapeutic mechanism of topical metformin fo...
OBJECTIVES: To evaluate the efficacy and safety of Q-switched Nd:YAG 1064 nm laser and topical 30% metformin lotion for treatment of chloasma in mice and explore the possible therapeutic mechanism of topical metformin for chloasma. METHODS: Forty female healthy Kunming mice were randomly divided into normal group (=16) and chloasma model group (=24), and the latter group was further divided into control, laser treatment, metformin lotion treatment, and laser with metformin (Laser+Met) treatment groups (=6). Chloasma was induced in the mouse models by medium-wave ultraviolet irradiation and intramuscular injection of progesterone. After 4 weeks of treatment, melanocyte count, melanin and tyrosinase activities of the mice were detected using immunohistochemistry and Western blotting, and the mRNA expressions of CRE/MITF signaling pathway-related proteins were detected with quantitative real-time PCR. RESULTS: The mouse models of chloasma receiving Laser+Met treatment had the lowest recurrence rate among the groups. After 4 weeks of treatment, melanocyte count and melanin and tyrosinase expressions, protein expressions of melanin and tyrosinase, and mRNA expressions of CREB1 and MITF in laser, metformin lotion, and Laser+Met groups were significantly reduced compared with those in the control group. Laser treatment and metformin lotion alone produced similar therapeutic effects in the mouse models, and the combined treatment achieved significantly better effects than either of them. CONCLUSIONS: Q-switched Nd:YAG 1064 nm laser combined 30% metformin lotion effectively shortens the treatment course and reduces recurrence rate of chloasma in mice with a good safety profile. The therapeutic effect of metformin lotion is mediated possibly by regulation of the cAMP/MITF signaling pathway and reduction of melanin and tyrosinase synthesis.
[Fecal microbiota transplantation inhibits colonic tumor growth in mice by suppressing the TLR4/MyD88/NF-κB signaling pathway].
Zhang J, Bai J, Ren X … +5 more , Ye X, Tan M, Yang Y, Li L, Fu Z
Nan Fang Yi Ke Da Xue Xue Bao · 2026 May · PMID 42198975 · Full text
OBJECTIVES: To explore the effects of fecal microbiota transplantation (FMT) on immune function and tumor inhibition in mice. METHODS: C57BL/6N mice were divided into blank control group, tumor bearing model group, and F...
OBJECTIVES: To explore the effects of fecal microbiota transplantation (FMT) on immune function and tumor inhibition in mice. METHODS: C57BL/6N mice were divided into blank control group, tumor bearing model group, and FMT intervention group (=6). In the latter two groups, the mice bearing subcutaneous MC38 colon cancer cell xenografts were treated with daily gavage of normal saline or 0.1 mL of bacterial suspension. The changes in tumor mass and volume were recorded, and peripheral blood natural killer (NK) cell counts and NKG2A and NKG2D receptor expressions were analyzed using flow cytometry; serum lipopolysaccharide (LPS) levels were measured with ELISA. The binding ability of NF‑κB to the TGF‑β1 gene promoter was analyzed with JASPAR. The mRNA and protein expressions of TLR4, MyD88, NF‑κB, TGF‑β1, perforin and granzyme in the tumor tissues were detected using RT qPCR and Western blotting, and the changes in gut microbiota were analyzed using 16S high throughput sequencing. RESULTS: FMT significantly reduced tumor mass and volume in the tumor-bearing mice. Peripheral CD3⁻NK1.1⁺ cell counts were significantly decreased in the tumor-bearing mice regardless of FMT treatment, which, however, reversed the increase of CD3NKG2A cells and reduction of CD3NKG2D cells and reduced serum LPS levels in the mouse models. Molecular docking and JASPAR analysis confirmed LPS-TLR4 binding (binding energy: -13.1 kcal/mol) and identified NF-κB binding sites on TGF‑β1 promoter. FMT downregulated mRNA and protein expressions of TLR4, MyD88, NF‑κB and TGF‑β1 and upregulated perforin and granzyme mRNA expressions in the xenografts. FMT also restored gut microbiota diversity and composition, and reversed the increase of and decrease of in the tumor-bearing mice. CONCLUSIONS: FMT modulates the relative abundances of intestinal and in tumor-bearing mice, and inhibits tumor growth by suppressing the TLR4/MyD88/NF‑κB signaling axis, down-regulating TGF-β1 expression, and promoting NK cell activation.
[ Decoction improves intestinal function in mouse models of Parkinson's disease by regulating intestinal bioactive substances].
Hou L, Tang L, Chen Q … +4 more , Sun J, Chen X, Li W, Zhao Y
Nan Fang Yi Ke Da Xue Xue Bao · 2026 May · PMID 42198974 · Full text
OBJECTIVES: To explore mechanism of Decoction (WSYG) for improving intestinal function in a mouse model of Parkinson's disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). METHODS: Sixty male C57...
OBJECTIVES: To explore mechanism of Decoction (WSYG) for improving intestinal function in a mouse model of Parkinson's disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). METHODS: Sixty male C57BL/6 mice were randomized equally into control group, MPTP group, low-, medium-, and high-dose WSYG groups (daily dose 10, 20 and 40 g/kg by gavage, respectively), and selegiline group. In all but the control group, the mice received intraperitoneal injections of MPTP (30 mg/kg) for 6 consecutive days to induce subacute PD. Motor function of the mice was assessed by the pole and open field tests, and striatal tyrosine hydroxylase (TH) expression, neuronal damage and intestinal histopathology were evaluated using immunohistochemistry, Nissl staining, and HE staining. Serum levels of diamine oxidase(DAO), D-lactic acid (D-LA), lipopolysaccharide (LPS), vasoactive intestinal peptide (VIP), and cholecystokinin (CCK) were measured by ELISA, intestinal expressions of tight junction proteins zonula occludens-1 (ZO-1) and occludin were an alyzed by immuno fluorescence staining, and intestinal barrier permeability was assessed using FITC-dextran. RESULTS: WSYG, especially at the medium and high doses, significantly improved the performance of the mice in the behavioral tests. WSYG at all the 3 doses reduced neuronal damage and Nissl body loss in the striatum and substantia nigra, its medium and high doses significantly increased TH-positive neurons in the striatum. WSYG at the 3 doses significantly decreased serum FITC-Dextran (MW 4000) level, and medium- and high-dose WSYG markedly alleviated colonic inflammatory infiltration and edema, increased the chorionic crypt ratio, and reduced loss of ZO-1 and occludin. WSYG at all the 3 doses significantly increased serum VIP and CCK levels and decreased DAO, D-LA and LPS levels in the mice. CONCLUSIONS: WSYG effectively improve motor deficits and intestinal dysfunction in PD mice possibly by up-regulating intestinal VIP/CCK and down-regulating DAO/D-LA/LPS expressions to reduce intestinal barrier permeability, thereby alleviating dopaminergic neuronal damage.
[Cephaeline attenuates malignant biological behaviors of colorectal cancer by regulating the Ras signaling pathway].
Han L, Li B, Wang B … +2 more , Zhang Z, Zhang J
Nan Fang Yi Ke Da Xue Xue Bao · 2026 May · PMID 42198973 · Full text
OBJECTIVES: To investigate the mechanism of cephaeline for suppressing malignant biological behaviors of colorectal cancer (CRC). METHODS: Network pharmacology was employed to identify the core targets and signaling path...
OBJECTIVES: To investigate the mechanism of cephaeline for suppressing malignant biological behaviors of colorectal cancer (CRC). METHODS: Network pharmacology was employed to identify the core targets and signaling pathways of cephaeline in CRC treatment. The binding between the key targets of CRC and cephaeline was simulated using molecular docking. CCK-8 assay was used to assess the viability of HCT116 and DLD-1 cells treated with 2-32 nmol/L cephaeline for 24, 48, and 72 h to determine the optimal treatment condition. The effects of cephaeline treatments (at 2 and 4 nmol/L in HCT116 cells and at 4 and 8 nmol/L in DLD-1 cells) for 48 h on cell proliferation, migration, invasion, epithelial‑mesenchymal transition (EMT), apoptosis, and expressions of RAS signaling pathway proteins were evaluated using colony-forming assay, wound healing assay, Transwell assays, and Western blotting. RESULTS: Network pharmacology analysis suggested that cephaeline inhibited CRC mainly by regulating the targets such as MAPK, VEGFA, and PDGFRB and modulating the Rap1, Ras, cAMP, and PI3K-Akt signaling pathways. Molecular docking results showed that the binding energies of cephaeline with PDGFRB and MAPK1 were less than -5 kcal/mol, indicating spontaneous and stable binding between them. In HCT116 and DLD-1 cells, treatment with cephaeline concentration-dependently suppressed the cell viability, proliferation, migration, and invasion, downregulated the expressions of PCNA, MMP9, VEGF-C, BCL-2, N-cadherin, vimentin, VEGF-A, PDGFRB, MYC, and MAPK1, and upregulated the expression levels of E-cadherin and BAX. CONCLUSIONS: Cephaeline suppresses malignant biological behaviors of CRC possibly by regulating the RAS signaling pathway.
[Petroleum ether fraction of roots relieves spasmodic abdominal pain in mice by inhibiting intestinal smooth muscle spasm].
Yang S, Chen W, Chen X … +6 more , Tian K, Xiong Y, Sun J, Huang L, Huang X, Wang Z
Nan Fang Yi Ke Da Xue Xue Bao · 2026 May · PMID 42198972 · Full text
OBJECTIVES: To investigate the effect of the petroleum ether fraction of roots (PEFM) for relieving spasmodic abdominal pain in mice and its underlying mechanism. METHODS: The chemical profile of PEFM was analyzed using...
OBJECTIVES: To investigate the effect of the petroleum ether fraction of roots (PEFM) for relieving spasmodic abdominal pain in mice and its underlying mechanism. METHODS: The chemical profile of PEFM was analyzed using GC-MS. Forty Kunming mice were randomized into 5 groups for daily gavage with solvent, dicyclomine, or low-, medium-, and high-dose PEFM for 5 consecutive days, and their effects against neostigmine-induced spasmodic abdominal pain were evaluated. Serum cGMP levels and ileal PKG and p-VASP expressions of the mice were measured. Acute toxicity of PEFM gavage at different doses was assessed in another 32 Kunming mice by monitoring behavioral changes and organ indices. An isolated ileal model of ACh-induced spasm was used to observe the antispasmodic effect of PEFM and its main constituent, stigmast-4-en-3-one (ST), and the mediating roles of the NO/sGC/cGMP/PKG pathway, potassium channels, and calcium channels were investigated using specific inhibitors and a high-potassium-induced spasm model. Molecular docking was used to predict the interactions between compounds and targets. RESULTS: PEFM contained mainly steroidal compounds, with ST as the most abundant component (31.51%). PEFM at the medium and high doses significantly reduced abdominal pain frequency, prolonged pain latency, and increased serum cGMP and ileal p-VASP expression without producing significant acute toxicity. Both PEFM and ST exhibited concentration-dependent antispasmodic effects against ACh-induced contractions (EC: 4.06 μg/mL and 0.53 μg/mL, respectively), which were inhibited by L-NAME, methylene blue, ODQ, and potassium channel blockers; they also strongly antagonized high potassium-induced contractions. Molecular docking confirmed stable binding of ST to PKG and p-VASP. CONCLUSIONS: PEFM has spasmolytic and analgesic effects in mice with neostigmine-induced spastic abdominal pain, mediated primarily by its main active component ST, which upregulates cGMP, enhances ileal VASP phosphorylation, activates NO/sGC/cGMP/PKG pathway, promotes opening of voltage-gated potassium channels, and antagonizes L-type calcium channels.
[ Granules inhibit cerebral microvascular endothelial cell apoptosis in hypertensive mice by suppressing the P53 signaling pathway].
Lin Y, Shi S, Wang J … +6 more , Lin S, Zhang J, Lin S, Chen Y, Zhang L, Cai Q
Nan Fang Yi Ke Da Xue Xue Bao · 2026 May · PMID 42198971 · Full text
OBJECTIVES: To investigate the mechanism by which Granules (QDG) inhibit apoptosis of hypertensive cerebral microvascular endothelial cells. METHODS: Eighteen C57BL/6 mice were randomized into control group, angiotensin...
OBJECTIVES: To investigate the mechanism by which Granules (QDG) inhibit apoptosis of hypertensive cerebral microvascular endothelial cells. METHODS: Eighteen C57BL/6 mice were randomized into control group, angiotensin II (AngII) group, and Ang II+QDG group (=6). The mice in the latter groups underwent subcutaneous implantation of a micropump for continuous infusion of Ang II (1000 ng·kg·min) to induce cerebral small vessel disease (CSVD) with daily gavage of saline or QDG (1.3 g/kg) for 4 weeks. Blood pressure of the mice was monitored weekly, cerebral microvascular morphology was assessed with HE staining, and the expressions of CD31, p53, cleaved caspase-3, cleaved caspase-9, Bcl-2 and Bax in the brain tissues were detected with immunohistochemistry and Western blotting. In a bEnd.3 cell model of oxygen and glucose deprivation/reoxygenation (OGD/R), the effects of QDG on cell viability and apoptosis were evaluated using CCK8 assay and Hoechst 33342 staining, respectively; the changes in mRNA expressions of P53, Bcl-2, and Bax and protein expressions of P53, Bcl-2, Bax, cleaved caspase-3 and cleaved caspase-9 were detected using RT-qPCR and Western blotting. RESULTS: Continuous infusion of Ang II resulted in significant elevation of systolic blood pressure, diastolic blood pressure, and mean arterial pressure in the mice, causing also widening of the perivascular space of the cerebral microvasculature, reduction of CD31 and Bcl-2 expressions, and increases in the expressions of p53, Bax, cleaved caspase-3, and cleaved caspase-9. All these changes were significantly mitigated by treatment with QDG. In bEnd.3 cells, QDG treatment significantly attenuated OGD/R-induced apoptosis, increased Bcl-2 expression, and decreased expressions of P53, Bax, cleaved caspase-3, and cleaved caspase-9. CONCLUSIONS: QDG suppress apoptosis of cerebral microvascular endothelial cells in hypertensive rats by downregulating the P53 signaling pathway to alleviate cerebral microvascular endothelial injury caused by hypertension.
[SENP1 reduces ferroptosis of thyroid cancer cells by regulating hypoxia-inducible factor-1α].
Zhu F, Yan N, Yang J … +2 more , Chen X, Wang Y
Nan Fang Yi Ke Da Xue Xue Bao · 2026 May · PMID 42198970 · Full text
OBJECTIVES: To explore the regulatory role of SENP1 in ferroptosis of differentiated thyroid cancer cells and its molecular mechanism. METHODS: TPC-1 cells transfected with sh-NC or sh-SENP1 plasmid were inoculated in nu...
OBJECTIVES: To explore the regulatory role of SENP1 in ferroptosis of differentiated thyroid cancer cells and its molecular mechanism. METHODS: TPC-1 cells transfected with sh-NC or sh-SENP1 plasmid were inoculated in nude mice (=6), and tumor growth was observed. In studies, TPC-1 cells were transfected with a SENP1-over expressing plasmid, si-USP11, or si-SENP1 via Lipofectamine 3000, followed by examination with CCK-8, EdU, LDH, Calcein/PI, and cytotoxicity assay kits. Mitochondrial function of the cells was evaluated using JC-1 depolymerization and mitochondrial permeability transition pore assays, and the changes in cellular protein expression levels were analyzed using Western Blotting. RESULTS: SENP1 knockdown in TPC-1 cells significantly inhibited tumor growth in nude mice. In TPC-1 cells, SENP1 overexpression significantly promoted cell proliferation and metastasis, and SENP1 knockdown produced the opposite effects. Functionally, SENP1 overexpression in TPC-1 cells obviously reduced the percentage of PI-positive cells and iron content and upregulated GPX4 protein levels, while the reverse changes were observed following si-SENP1 transfection. SENP1 overexpression also enhanced JC-1 depolymerization, increased calcein-AM/cobalt chloride fluorescence and extracellular acidification rate, and decreased oxygen consumption rate, indicating reduced mitochondrial damage. Conversely, si-SENP1 transfection exacerbated mitochondrial injury in TPC-1 cells. SENP1 overexpression significantly enhanced the protein level of hypoxia-inducible factor-1α, which was obviously lowered following sh-SENP1 transfection in TPC-1 cells. CONCLUSIONS: High expression of SENP1 inhibits mitochondrial damage, reduces ferroptosis, and promotes proliferation of thyroid cancer cells by activating HIF-1α, suggesting the potential of SENP1 as a novel therapeutic target for thyroid cancer.
[Liraglutide improves cardiac structure and function in mice with advanced diabetic nephropathy and massive proteinuria].
Yan Y, Yang W, Li W … +3 more , Yang C, Wang F, Wang J
Nan Fang Yi Ke Da Xue Xue Bao · 2026 May · PMID 42198969 · Full text
OBJECTIVES: To investigate the effects of liraglutide on cardiac structure and function in a mouse model of diabetic nephropathy at the massive proteinuria stage. METHODS: Twenty 12-week-old male spontaneous type 2 diabe...
OBJECTIVES: To investigate the effects of liraglutide on cardiac structure and function in a mouse model of diabetic nephropathy at the massive proteinuria stage. METHODS: Twenty 12-week-old male spontaneous type 2 diabetic KKAy mice were fed a high-fat diet for 10 weeks to establish diabetic models with massive proteinuria, which were then randomly divided into diabetic model group and liraglutide treatment group, with 10 age-matched C57BL/6J mice fed a standard chow diet serving as the normal control group. After 8 weeks of intervention, cardiac structural and functional parameters of the mice were evaluated using echocardiography, and myocardial histopathological changes were observed with HE staining, Masson's trichrome staining, Sirius red staining, and transmission electron microscopy. Serum levels of cardiac-related indicators were measured, and the mRNA and protein levels of collagen I and collagen III were determined using RT-qPCR and Western blotting, respectively. RESULTS: The diabetic mouse models showed significantly elevated blood glucose and increased body weight (<0.05) with disordered myocardial fibers, severe interstitial and perivascular fibrosis, and markedly upregulated myocardial expressions of collagen I and collagen III. Echocardiography revealed significantly increased left ventricular wall thickness, interventricular septal thickness, and left ventricular mass, reduced left ventricular internal diameter, decreased LVEF, FS, FAC, and the E/A ratio, and prolonged IVRT in the mouse models. Liraglutide treatment significantly improved these pathologies and alleviated cardiac functional impairment in the diabetic mice. CONCLUSIONS: Mice with diabetic nephropathy and massive proteinuria exhibit left ventricular hypertrophy and reduced cardiac function, accompanied by prominent myocardial interstitial fibrosis and inflammatory responses. Liraglutide improves cardiac structural and functional impairments in these mice possibly by alleviating myocardial fibrosis and inflammatory responses.
[Growth differentiation factor 11 attenuates hypoxia/reoxygenation injury in rat H9C2 cardiomyocytes by inhibiting thioredoxin-1 nitrative inactivation].
Wei J, Jiang W, Xia L … +2 more , Lü L, Yang Q
Nan Fang Yi Ke Da Xue Xue Bao · 2026 May · PMID 42198968 · Full text
OBJECTIVES: To verify the hypothesis that growth differentiation factor 11 (GDF11) attenuates myocardial ischemia/reperfusion (MI/R) injury and explore the underlying mechanism. METHODS: To simulate MI/R injury, H9C2 cel...
OBJECTIVES: To verify the hypothesis that growth differentiation factor 11 (GDF11) attenuates myocardial ischemia/reperfusion (MI/R) injury and explore the underlying mechanism. METHODS: To simulate MI/R injury, H9C2 cells were incubated in an anaerobic chamber (95% N+5% CO) for 9 h followed by 3 h of reoxygenation in the presence of GDF11 (10 nmol/L). The cells exposed to hypoxia/reoxygenation (H/R) or sham exposure were treated with GDF11 alone or in combination with the iNOS inhibitor 1400W, the Trx1 nitration inhibitor EUK134, human recombinant Trx1 (hTrx1) or N-Trx1, and the changes in cell viability was determined by MTT assay and LDH release assay. Cardiomyocyte apoptosis was determined by TUNEL staining and caspase-3 activity assessment, and oxidative stress levels were evaluated by measuring superoxide production and DHE staining. Nitrative stress in the cells was assessed by measuring total NO content and nitrotyrosine content. The expression levels of iNOS, gp91phox, ASK1 and p-ASK1 were detected using Western blotting, Trx1 activity was determined using insulin disulfide reduction assay, and Trx1 nitration was analyzed by immunoprecipitation. RESULTS: In H9C2 cells with H/R exposure, 10 nmol/L GDF11 treatment significantly increased cell viability, decreased LDH release, inhibited caspase-3 activation and cell apoptosis, and reduced superoxide production, total NO content and nitrotyrosine production. GDF11 also significantly inhibited iNOS expression, reversed H/R-induced increase of Trx1 nitration and inhibition of Trx1 activity, and inhibited ASK1 phosphorylation. Treatment of the cells with 1400W decreased LDH release and caspase-3 activity, and diminished total NO production and nitrotyrosine production. EUK134 diminished LDH release and caspase-3 activation, upregulated Trx activity, and inhibited superoxide production in H9C2 cells. N-Trx1 abolished the protective effects of GDF11 against H/R injury in the cardiomyocytes. CONCLUSIONS: GDF11 protects cardiomyocytes against H/R injury partially by attenuating oxidative/nitrative stress and inhibiting Trx1 nitrative inactivation.
[Ethanol promotes oxaliplatin resistance in colorectal cancer by activating the TGF‑β/Smad/P21 signaling axis].
Tan B, Weng N, Zeng W … +5 more , Gu J, Weng L, Wen H, Xiao H, Zheng K
Nan Fang Yi Ke Da Xue Xue Bao · 2026 May · PMID 42198967 · Full text
OBJECTIVES: To investigate the effect of ethanol for promoting oxaliplatin resistance in colorectal cancer (CRC) and the underlying molecular mechanisms. METHODS: Lifetime alcohol consumption data from the PLCO cohort we...
OBJECTIVES: To investigate the effect of ethanol for promoting oxaliplatin resistance in colorectal cancer (CRC) and the underlying molecular mechanisms. METHODS: Lifetime alcohol consumption data from the PLCO cohort were analyzed to assess the association between alcohol drinking and CRC risk. The differential expressions of alcohol metabolism-related genes between CRC and normal tissues and their associations with recurrence and survival in chemotherapy-treated patients were analyzed based on GEO datasets. Fecal samples from healthy non-drinkers and CRC patients were collected for detecting ethanol levels using gas chromatography-mass spectrometry (GC-MS). In a mouse model bearing subcutaneous CRC xenograft treated with oxaliplatin, the effects of continuous ethanol exposure using the Lieber-DeCarli liquid diet and 4-methylpyrazole (4-MP) treatment on tumor growth were evaluated. In cultured SW480 and HCT116 cells, the effect of 100 and 200 mg/dL ethanol on oxaliplatin sensitivity, apoptosis, cell cycle distribution, and TGF‑β/Smad/P21/Rb axis proteins were analyzed, and the results were further validated with pirfenidone intervention experiment. RESULTS: High-frequency drinkers had a significantly increased risk of CRC. ADH1B and ADH1C were significantly downregulated in CRC tissues, and their low expressions were associated with a higher recurrence rate and poorer overall survival in chemotherapy-treated patients. Ethanol was detected in fecal samples from both healthy individuals and CRC patients. In oxaliplatin-treated tumor-bearing mice, alcohol exposure resulted in a greater tumor volume. In SW480 and HCT116 cells, ethanol significantly increased oxaliplatin IC₅₀, reduced cell apoptosis, induced G0/G1 arrest, decreased S-phase fraction, and upregulated TGF-β1, p-Smad2, and P21 while downregulating p-Rb expression. Pirfenidone partially reversed these changes and attenuated drug resistance of the cells. CONCLUSIONS: Ethanol accumulation activates the TGF-β/Smad/P21 axis to induce cell cycle arrest and promote oxaliplatin resistance in CRC cells, which can be partially reversed by pirfenidone inhibition.
[Establishment of an gastric dysfunction and depression comorbidity model simulating clinical etiology in mice using a combined stress protocol].
Huang Q, Shen W, Hu J … +5 more , Ma H, Hu Y, Zhang C, Shen G, Wang H
Nan Fang Yi Ke Da Xue Xue Bao · 2026 May · PMID 42198966 · Full text
OBJECTIVES: To establish a mouse model with the comorbidity of gastric dysfunction and depression mimicking clinical onset of the condition. METHODS: Thirty male C57BL/6J mice were randomly divided into control, 14-day m...
OBJECTIVES: To establish a mouse model with the comorbidity of gastric dysfunction and depression mimicking clinical onset of the condition. METHODS: Thirty male C57BL/6J mice were randomly divided into control, 14-day model, and 28-day model groups (=10). The mice in the latter two groups were subjected to continuous combined stresses induced by tail clamping, cold-saline gavage and irregular feeding for 14 or 28 days. Gastric motility, gastric emptying and histopathological changes of the mice were evaluated using strain gauge sensors, imaging and HE staining, respectively, and behavioral tests were used to assess their depression-like behaviors. Serum corticotropin-releasing factor (CRF), brain-derived neurotrophic factor (BDNF), gastrin, motilin, and gastric nitric oxide synthase (NOS) and acetylcholinesterase (AChE) levels were measured by ELISA to explore the peripheral mechanisms. RESULTS: Compared with control mice, the mice in 14-day model group exhibited reduced body weight, food intake and gastric motility amplitude with delayed gastric emptying but showed no significant depression-like behaviors; in 28-day model group, these changes were further exacerbated, and significant depression-like behaviors were observed. Compared with 14-day model group, the 28-day model group displayed severer gastric dysfunction and depression-like behaviors. Compared with control group, exposure to complex stresses for 14 days significantly increased serum CRF and decreased BDNF, gastrin and motilin levels, increased gastric NOS and decreased gastric AChE level, which were worsened after a 28-day exposure. HE staining showed no obvious histological changes in the gastric mucosa in the two model groups. CONCLUSIONS: Combined stresses induced by tail clamping, cold-saline gavage and irregular feeding for 28 days can induced the comorbidity of gastric dysfunction and depression in mice, and abnormal changes in serum neurotransmitters, brain-gut peptides and vagus activity may partly participate in the pathogenesis of the comorbidity.
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