Objective To investigate the regulatory mechanism of transforming growth factor-β1 (TGF-β1) in different types of mitral valvular disease (MVD) with atrial fibrillation (AF). Methods From August 2011 to August 2012, patients with moderate to severe MVD accompanied by AF who required mitral valve replacement at the Department of Cardiovascular Surgery, West China Hospital, Sichuan University, were included. Based on echocardiographic results, patients were divided into two groups: a mitral regurgitation (MR) with AF (MR-AF) group and a mitral stenosis (MS) with AF (MS-AF) group. Left atrial tissue samples were collected during surgery. Techniques such as enzyme-linked immunosorbent assay, real-time fluorescence quantitative polymerase chain reaction, immunohistochemistry, and Western blotting were used to detect key molecules in the TGF-β1/JNK pathway. Results Sixteen patients were enrolled. There were 8 patients in the MR-AF group, including 5 males and 3 females, with an average age of (41.38±11.19) years; and 8 patients in the MS-AF group, including 6 males and 2 females, with an average age of (43.12±5.30) years. The left atrial volume load was higher in MR-AF patients, while the left atrial pressure load was higher in MS-AF patients. In MS-AF patients, the relative expression levels of MAPK9, JUN, CASP3, BAX, and BCL2 mRNA in left atrial tissues were significantly upregulated. The serum TGF-β1 protein level and the relative expression levels of p-JNK, p-c-Jun, and Caspase-3 proteins in the left atrial tissues of the MR-AF group were higher. Myocardial cell damage was more severe in the MS-AF group, and the protein expression level of Bcl-2 was higher. Conclusion Different MVD have distinct hemodynamic characteristics. The myocardium of the left atrium in MR-AF patients is more prone to apoptosis, possibly through the activation of the TGF-β1/JNK signaling pathway.

ObjectiveTo explore the changes in color， odor and chemical components during wine-processing of Chuanxiong Rhizoma（CR）， identify differential markers， and provide a basis for standardizing the process and establishing quality standards. MethodsFifteen batches of CR samples from 4 producing areas were collected. Colorimeter and electronic nose were used to detect the color changes and odor components of CR before and after wine-processing. Multivariate statistical methods including partial least squares-discriminant analysis（PLS-DA）， principal component analysis（PCA）， discriminant factor analysis（DFA） and Fisher discriminant analysis were applied to identify wine-processed CR at different processing stages and establish discriminant models， and differential components were screened out based on variable importance in the projection（VIP） value1. Then， high performance liquid chromatography（HPLC） was employed to detect the content changes of four components（ferulic acid， senkyunolide I， senkyunolide A and ligustilide） during the processing stages. ResultsThe differences of wine-processed CR at various stages were primarily reflected in color parameters L^*（brightness value）， a^*（red-green value） and b^*（yellow-blue value）. Based on chromaticity differences， the color reference ranges were established for moderately processed CR， including L^* of 46.75-48.24， a^* of 5.37-6.07 and b^* of 20.32-21.70. In odor analysis， DFA revealed significant differences among processing stages， and 11 odor markers were identified， with four differential markers（4-hydroxy-3-butylphthalide， isopropyl butyrate， L-limonene and 1-methoxyhexane） based on VIP values. HPLC results showed that there was no significant difference of the four components except for ligustilide in wine-processed CR at different stages. ConclusionThis study achieved rapid identification of wine-processed CR with different processing degrees by electronic sensory technology and differential component content detection， with discrimination accuracy rates of 92.4% and 93.272% for color and odor， respectively. This paper also established the reference ranges of main colorimetric parameters for wine-processed CR at different stages， and four differential components were screened out， providing a basis for standardizing the processing of wine-processed CR and establishing quality standards for this decoction pieces.

ObjectiveTo explore the changes in color， odor and chemical components during wine-processing of Chuanxiong Rhizoma（CR）， identify differential markers， and provide a basis for standardizing the process and establishing quality standards. MethodsFifteen batches of CR samples from 4 producing areas were collected. Colorimeter and electronic nose were used to detect the color changes and odor components of CR before and after wine-processing. Multivariate statistical methods including partial least squares-discriminant analysis（PLS-DA）， principal component analysis（PCA）， discriminant factor analysis（DFA） and Fisher discriminant analysis were applied to identify wine-processed CR at different processing stages and establish discriminant models， and differential components were screened out based on variable importance in the projection（VIP） value1. Then， high performance liquid chromatography（HPLC） was employed to detect the content changes of four components（ferulic acid， senkyunolide I， senkyunolide A and ligustilide） during the processing stages. ResultsThe differences of wine-processed CR at various stages were primarily reflected in color parameters L^*（brightness value）， a^*（red-green value） and b^*（yellow-blue value）. Based on chromaticity differences， the color reference ranges were established for moderately processed CR， including L^* of 46.75-48.24， a^* of 5.37-6.07 and b^* of 20.32-21.70. In odor analysis， DFA revealed significant differences among processing stages， and 11 odor markers were identified， with four differential markers（4-hydroxy-3-butylphthalide， isopropyl butyrate， L-limonene and 1-methoxyhexane） based on VIP values. HPLC results showed that there was no significant difference of the four components except for ligustilide in wine-processed CR at different stages. ConclusionThis study achieved rapid identification of wine-processed CR with different processing degrees by electronic sensory technology and differential component content detection， with discrimination accuracy rates of 92.4% and 93.272% for color and odor， respectively. This paper also established the reference ranges of main colorimetric parameters for wine-processed CR at different stages， and four differential components were screened out， providing a basis for standardizing the processing of wine-processed CR and establishing quality standards for this decoction pieces.

Speech imagery is an emerging brain-computer interface (BCI) paradigm with potential to provide effective communication for individuals with speech impairments. This study designed a Chinese speech imagery paradigm using three clinically relevant words-"Help me", "Sit up" and "Turn over"-and collected electroencephalography (EEG) data from 15 healthy subjects. Based on the data, a Channel Attention Multi-Scale Convolutional Neural Network (CAM-Net) decoding algorithm was proposed, which combined multi-scale temporal convolutions with asymmetric spatial convolutions to extract multidimensional EEG features, and incorporated a channel attention mechanism along with a bidirectional long short-term memory network to perform channel weighting and capture temporal dependencies. Experimental results showed that CAM-Net achieved a classification accuracy of 48.54% in the three-class task, outperforming baseline models such as EEGNet and Deep ConvNet, and reached a highest accuracy of 64.17% in the binary classification between "Sit up" and "Turn over". This work provides a promising approach for future Chinese speech imagery BCI research and applications.
Humans ; Electroencephalography/methods* ; Brain-Computer Interfaces ; Neural Networks, Computer ; Speech/physiology* ; Algorithms ; Male ; Adult ; Imagination

Objective To investigate the role and mechanism of RNA-Specific adenosine deaminase 3 (Adar3) in regulating macrophage polarization during Coxsackievirus B3(CVB3)-induced viral myocarditis (VM). Methods Bone marrow-derived macrophages (BMDM) from mice were cultured in vitro and induced into M1/M2 macrophages using interferon-gamma (IFN-γ)/lipopolysaccharide (LPS) or interleukin 4 (IL-4), respectively. The mRNA expression levels of Adar1, Adar2, and Adar3 in each group of cells were assessed by real-time quantitative PCR (qRT-PCR). Specific siRNAs targeting the Adar3 gene were designed, synthesized, and transiently transfected into M2 macrophages. The mRNA levels of M2 polarization-related marker genes-including arginase 1 (Arg1), chitinase 3-like molecule 3 (YM1/Chi3l3), and resistin-like molecule alpha (RELMα/FIZZ1)-were detected by qRT-PCR. RNA sequencing was performed to analyze the signaling pathways affected by Adar3. The expression levels of Wnt/β-catenin signaling pathway were further validated using qRT-PCR and Western blot. The adeno-associated virus overexpressing Adar3 was designed, synthesized, and injected into mice via tail vein. Three weeks later, a myocarditis mouse model was established. After an additional week, the phenotype and function of cardiac macrophages, as well as multiple indicators of VM (including echocardiography, body weight, histopathology and serology) were examined. Additionally, the protein levels of the Wnt/β-catenin signaling pathway were assessed. Results Compared to M0-type macrophages, the expression level of Adar3 was significantly increased in M2-type macrophages. After transfection of Adar3 siRNA, the mRNA levels of Arg1, YM1 and FIZZ1 in M2 macrophages were downregulated. RNA sequencing revealed 149 upregulated genes and 349 downregulated genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and subsequent validation experiments indicated that Adar3 modulated the Wnt/β-catenin signaling pathway. In vivo experiments demonstrated that Adar3 overexpression alleviated the cardiac dysfunction of VM mice. The proportion of M1 macrophages in the heart decreased, while the proportion of M2 macrophages increased. At the same time, the Adar3 overexpression activated the Wnt/β-catenin signaling pathway. Conclusion Adar3 promotes macrophage polarization toward the M2 phenotype by activating the Wnt/β-catenin signaling pathway, thereby alleviating VM.
Animals ; Adenosine Deaminase/metabolism* ; Macrophages/immunology* ; Wnt Signaling Pathway/genetics* ; Myocarditis/immunology* ; Mice ; Coxsackievirus Infections/metabolism* ; Male ; Mice, Inbred BALB C ; Enterovirus B, Human/physiology* ; beta Catenin/genetics*

PURPOSE: Postpancreatectomy hemorrhage (PPH) is a life-threatening complication after pancreatoduodenectomy. Stent-graft implantation is an emerging treatment option for PPH. This study reports the outcome of PPH treated with stent-graft implantation. METHODS: This was a single-center, retrospective study. Between April 2020 and December 2023, 1723 pancreatectomy cases were collected while we screened 12 cases of PPH after pancreatoduodenectomy treated with stent-graft implantation. Patients' medical and radiologic images were retrospectively reviewed. Technical and clinical success, complications, and stent-graft patency were evaluated. Continuous data are reported as means ± standard deviation when normally distributed or as median (Q₁, Q₃) when the data is non-normal distributed. Categorical data are reported as n (%). A p < 0.05 was considered statistically significant. Kaplan-Meier estimates were used for stent patency and patients' survival. RESULTS: Pancreatic fistula was identified in 6 cases (50.0%), and pseudoaneurysm was identified in 3 cases (25.0%), including pancreatic fistula together with pseudoaneurysm in 1 case (8.3%). All pseudoaneurysm or contrast extravasation sites were successfully excluded with patent distal perfusion, thus technical success was achieved in all cases. The overall survival rate at 6 months and 1 year was 91.7% and 78.6%, respectively. One patient had herniation of the small intestine into the thoracic cavity, which caused a broad thoracic and abdominal infection and died during hospitalization. Rebleeding occurred at the gastroduodenal artery stump in 1 case after stent-graft implantation for the splenic artery and was successfully treated with another stent-graft implantation. Two cases of asymptomatic stent-graft occlusion were observed at 24.6 and 26.3 after the operation, respectively. CONCLUSIONS With suitable anatomy, covered stent-graft implantation is an effective and safe treatment option for PPH with various bleeding sites and causes.
Humans ; Pancreaticoduodenectomy/adverse effects* ; Stents ; Male ; Retrospective Studies ; Female ; Middle Aged ; Postoperative Hemorrhage/surgery* ; Aged ; Adult

Homeostasis and energy and substance metabolism reprogramming shape various tumor microenvironment to sustain cancer stemness, self-plasticity and treatment resistance. Aiming at them, a lipid-based pharmaceutical loaded with CaO₂ and glucose oxidase (GOx) (LipoCaO₂/GOx, LCG) has been obtained to disrupt calcium homeostasis and interfere with glycometabolism. The loaded GOx can decompose glucose into H₂O₂ and gluconic acid, thus competing with anaerobic glycolysis to hamper lactic acid (LA) secretion. The obtained gluconic acid further deprives CaO₂ to produce H₂O₂ and release Ca²⁺, disrupting Ca²⁺ homeostasis, which synergizes with GOx-mediated glycometabolism interference to deplete glutathione (GSH) and yield reactive oxygen species (ROS). Systematical experiments reveal that these sequential multifaceted events unlocked by Ca²⁺ homeostasis disruption and glycometabolism interference, ROS production and LA inhibition, successfully enhance cancer immunogenic deaths of breast cancer cells, hamper regulatory T cells (Tregs) infiltration and promote CD8⁺ T recruitment, which receives a considerably-inhibited outcome against breast cancer progression. Collectively, this calcium homeostasis disruption glycometabolism interference strategy effectively combines ion interference therapy with starvation therapy to eventually evoke an effective anti-tumor immune environment, which represents in the field of biomedical research.

Gastrointestinal (GI) cancers are a leading cause of cancer morbidity and mortality worldwide. Despite advances in treatment, cancer relapse remains a significant challenge, necessitating novel therapeutic strategies. In this study, we engineered nanobody-based chimeric antigen receptor (CAR) natural killer (NK) cells targeting cadherin 17 (CDH17) for the treatment of GI tumors. In addition, to enhance the efficacy of CAR-NK cells, we also incorporated CV1, a CD47-SIRPα axis inhibitor, to evaluate the anti-tumor effect of this combination. We found that CDH17-CAR-NK cells effectively eliminated GI cancers cells in a CDH17-dependent manner. CDH17-CAR-NK cells also exhibit potent in vivo anti-tumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the anti-tumor activity of CDH17-CAR-NK cells is synergistically enhanced by CD47-signal regulatory protein α (SIRPα) axis inhibitor CV1, likely through augmented macrophages activation and an increase in M1-phenotype macrophages in the tumor microenvironment. Collectively, our findings suggest that CDH17-targeting CAR-NK cells are a promising strategy for GI cancers. The combination of CDH17-CAR-NK cells with CV1 emerges as a potential combinatorial approach to overcome the limitations of CAR-NK therapy. Further investigations are warranted to speed up the clinical translation of these findings.

Objective:To investigate the effects of spinal cord injury(SCI)on neuropathic pain(NP)and cognitive dysfunction in mice,as well as the activation of neurons in the anterior cingulate cortex(ACC),in order to provide experimental evidence for the connection between NP and cognitive dysfunction following SCI.Methods:Ten 8-week-old male C57BL/6J mice were used to prepare a model of spinal cord hemisection(SCI).Pain behavior and cognitive function of mice after SCI were assessed using von Frey,thermal stimulation,and Morris water maze behavioral experi-ments.Immunofluorescence staining were used to analyze the expression of c-Fos and GAD67/VGLUT2 positive cells in the anterior cingulate cortex(ACC)of the SCI model mice.Results:Compared with the Sham group,the SCI group of mice showed a significant decrease in mechanical threshold and thermal pain threshold(P＜0.05).The Morris water maze results indicated a significantly prolonged escape latency(P＜0.05)and a significant reduction in the use of search strategies for locating the hidden platform.Immunofluorescence results showed a significant increase in the num-ber of c-Fos positive cells in the ACC(P＜0.05),which were mainly co-labeled with excitatory neuron marker VGLUT2 positive cells.Conclusion:SCI leads to abnormal pain behavior and cognitive dysfunction in mice,and it induces the activation of neurons in the ACC,with a predominant activation of excitatory neurons.This study provides morphological evidence for the involvement of excitatory neurons in the ACC in the comorbidity of NP and cognitive impairment following SCI.

Chronic thromboembolic pulmonary hypertension(CTEPH)is a severe form of pulmonary hypertension(PH),and is classified as the fourth major category of pulmonary arterial hypertension.CTEPH is primarily caused by chronic thrombosis,leading to the obstruction of blood flow in the pulmonary arteries and result ing in a sustained increase in pulmonary artery pressure.The unclear pathogenesis of CTEPH,however,means that its early diagnosis is challenging,treatment options are limited,and prognosis assessment is often inaccurate.In-depth research into these mechanisms will thus improve our understanding of the pathophysiological processes of CTEPH,and also provide a theoretical basis for developing new therapeutic strategies.This review focuses on the current method of establishing CTEPH rat models and their advantages and disadvantages,offering researchers a reference for selecting and constructing CTEPH rat models.