1.Mechanism of Naoxintong Capsules in treatment of rats with multiple cerebral infarctions and myocardial injury based on HIF-1α/VEGF pathway.
Xiao-Lu ZHANG ; Jin-Feng SHANG ; Yin-Lian WEN ; Gui-Jin-Feng HUANG ; Bo-Hong WANG ; Wan-Ting WEI ; Wen-Bin CHEN ; Xin LIU
China Journal of Chinese Materia Medica 2025;50(7):1889-1899
This study aims to explore whether Naoxintong Capsules improve multiple cerebral infarctions and myocardial injury via promoting angiogenesis, thereby exerting a simultaneous treatment effect on both the brain and heart. Male SD rats were randomly divided into six groups: sham-operated group, model group, high-dose, medium-dose, and low-dose groups of Naoxintong Capsules(440, 220, and 110 mg·kg~(-1)), and nimodipine group(10.8 mg·kg~(-1)). Rat models of multiple cerebral infarctions were established by injecting autologous thrombus, and samples were collected and tested seven days after modeling. Evaluations included multiple cerebral infarction model assessments, neurological function scores, grip strength tests, and rotarod tests, so as to evaluate neuromotor functions. Morphological structures of brain and heart tissue were observed using hematoxylin-eosin(HE) staining, Nissl staining, and Masson staining. Network pharmacology was employed to screen the mechanisms of Naoxintong Capsules in improving multiple cerebral infarctions and myocardial injury. Neuronal and myocardial cell ultrastructures were observed using transmission electron microscopy. Apoptosis rate in brain neuronal cells was detected by TdT-mediated dUTP nick end labeling(TUNEL) staining, and reactive oxygen species(ROS) levels in myocardial cells were measured. Immunofluorescence was used to detect the expression of platelet endothelial cell adhesion molecule-1(CD31), antigen identified by monoclonal antibody Ki67(Ki67), hematopoietic progenitor cell antigen CD34(CD34), and hypoxia inducible factor-1α(HIF-1α) in brain and myocardial tissue. Western blot, and real-time quantitative polymerase chain reaction(RT-qPCR) were used to detect the expression of HIF-1α, vascular endothelial growth factor(VEGF), vascular endothelial growth factor receptor 2(VEGFR2), sarcoma(Src), basic fibroblast growth factor(bFGF), angiopoietin-1(Ang-1), and TEK receptor tyrosine kinase(Tie-2). Compared with the model group, the medium-dose group of Naoxintong Capsules showed significantly lower neurological function scores, increased grip strength, and prolonged time on the rotarod. Pathological damage in brain and heart tissue was reduced, with increased and more orderly arranged mitochondria in neurons and cardiomyocytes. Apoptosis in brain neuronal cells was decreased, and ROS levels in cardiomyocytes were reduced. The microvascular density and endothelial cells of new blood vessels in brain and heart tissue increased, with increased overlapping regions of CD31 and Ki67 expression. The relative protein and mRNA expression levels of HIF-1α, VEGF, VEGFR2, Src, Ang-1, Tie-2, and bFGF were elevated in brain tissue and myocardial tissue. Naoxintong Capsules may improve multiple cerebral infarctions and myocardial injury by mediating HIF-1α/VEGF expression to promote angiogenesis.
Animals
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Male
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Drugs, Chinese Herbal/administration & dosage*
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Rats, Sprague-Dawley
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Rats
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Cerebral Infarction/genetics*
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Hypoxia-Inducible Factor 1, alpha Subunit/genetics*
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Vascular Endothelial Growth Factor A/genetics*
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Capsules
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Signal Transduction/drug effects*
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Humans
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Brain/metabolism*
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Myocardium/metabolism*
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Apoptosis/drug effects*
2.Psychological stress-activated NR3C1/NUPR1 axis promotes ovarian tumor metastasis.
Bin LIU ; Wen-Zhe DENG ; Wen-Hua HU ; Rong-Xi LU ; Qing-Yu ZHANG ; Chen-Feng GAO ; Xiao-Jie HUANG ; Wei-Guo LIAO ; Jin GAO ; Yang LIU ; Hiroshi KURIHARA ; Yi-Fang LI ; Xu-Hui ZHANG ; Yan-Ping WU ; Lei LIANG ; Rong-Rong HE
Acta Pharmaceutica Sinica B 2025;15(6):3149-3162
Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.
3.Advances of Metal-Organic Framework Stationary Phases for Gas Chromatographic Separations
Yan JIN ; Wen-Bo LI ; Yu-Chen ZHU ; Bin ZHAO ; Lei LI ; Dan ZHENG ; Fei FENG
Chinese Journal of Analytical Chemistry 2025;53(1):1-13
Metal-organic frameworks(MOFs)are porous materials composed of metal ions or metal clusters and organic ligands by coordination,which have the advantages of large specific surface area,good thermal stability and adjustable pore size,and have a promising application in gas chromatographic separation.In recent years,MOFs materials have been used as stationary phases for gas chromatography mainly including ZIF,MIL,UiO-66,HKUST-1,IRMOFs,etc.Based on the molecular sieve effect,van der Waals forces,hydrogen bonding and π-π interactions,the pore size,pore microenvironment,unsaturated metal site and special functional group of the MOFs stationary phase materials can be specifically designed and regulated.MOFs materials as stationary phases have unique separation performance for n-alkanes and their isomers,aromatic compounds and their isomers,alcohols/ketones/aldehydes and their isomers,and chiral compounds.The combination of organic polymers and novel nanomaterials with MOFs materials can improve the separation performance and stability of MOFs.Therefore,MOFs materials are expected to be the promising stationary phase that can be applied to gas separation in complex environments.In this article,the research advances of various stationary phases based on MOFs for gas chromatography in recent years were reviewed.The separation performance and separation mechanism of MOFs stationary phases for mixed gas samples were discussed,and the development trends in the future were prospected.
4.Establishment and evaluation of a lipopolysaccharide-induced acute respiratory distress syndrome model in minipigs
Chuang-Ye WANG ; Ran WANG ; Jian ZHANG ; Ling-Xiao QIU ; Bin QING ; Heng YOU ; Jin-Cheng LIU ; Bin WANG ; Nan-Bo WANG ; Jia-Yu LI ; Xing LIU ; Shuang WANG ; Jin HU ; Jian WEN ; Quan LI ; Xiao-Ou HUANG ; Kun ZHAO ; Shuang-Lin LIU ; Gang LIU ; Mei-Ju WANG ; Qing XIANG ; Hong-Mei WU ; Xiao-Rong SUN ; Tao GU ; Dong ZHANG ; Qi LI ; Zhi XU
Medical Journal of Chinese People's Liberation Army 2025;50(9):1154-1161
Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.
5.Thoughts and Methods of Soothing Liver and Regulating the Mind Integrated Acupuncture and Moxibustion Programme for the Treatment of Perimenopausal Insomnia
Zi-Jin QIN ; Yi-Rong ZHOU ; Wen-Bin FU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(5):1220-1226
Perimenopausal insomnia is referred to as"syndromes occured before and after amenorrhea","insomnia"and"visceral irritability"in traditional Chinese medicine.It is believed that yin deficiency of the liver and kidney leads to liver constraint transforming into fire,which harassing the upper body of the heart and spirit,as well as qi and blood insufficiency that leads to the dysfunction of liver,which is the main pathogenesis of perimenopausal insomnia.Therefore,the treatment method of soothing the liver and regulating the mind is proposed,and combined with acupuncture,fine moxibustion,pricking collaterals,auricular acupuncture,back-shu point embedding acupuncture and other treatment methods,which together constitute the"firstly applying needling,secondly using moxibustion,thirdly focusing on consolidation"integrated acupuncture and moxibustion program to provide treatment ideas for perimenopausal insomnia.
6.Analysis of FU Wen-Bin's Experience in the Treatment of Radiation Encephalopathy
Jin-Feng GAO ; Shan-Ze WANG ; Ying DENG ; Xi-Chang HUANG ; Si-Bo WEI ; Wen-Bin FU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(6):1493-1498
Based on the principle of'treating disease and seeking the root cause',Professor FU Wen-Bin proposed'treating radiation encephalopathy(REP)from yang',pointing out that the main pathogenesis of REP is yang qi deficiency,brain spirit dystrophy,phlegm and blood stasis blocking orifices.Using'supplementing yang and unblocking yang simultaneously','treating spirit from heart and gallbladder',combined with the method of regulating spirit and unblocking orifices at acupoints of governor vessol and conception vessel,and using the integrated acupuncture mode of'firstly applying needling,secondly using moxibustion,thirdly focusing on consolidation'to play the role of supporting yang and treating spirit can effectively relieve symptoms and delay the development of the disease.
7.Exploration of the Pathogenesis of Inflammation-to-Tumor Transition in Chronic Atrophic Gastritis and Thoughts for Its Syndrome Differentiation and Treatment by LIU Feng-Bin
Xiao-Tao JIANG ; Pei-Wu LI ; Ze-Hong YANG ; Jin-Qi AN ; Yuan-Cheng HUANG ; Yi WEN ; Feng-Bin LIU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(7):1880-1885
Chronic atrophic gastritis(CAG)is a common intractable gastric disease in clinic,which belongs to the gastric precancerous lesions.Professor LIU Feng-Bin and his team have performed the exploration and practice in the field of CAG for more than 30 years,and they proposed that the evolution of the traditional Chinse medicine(TCM)pathogenesis of inflammation-to-tumor transition(ITT)in CAG was characterized by spleen deficiency being the root cause,qi stagnation,blood stasis and dampness retention being the branch cause,and stasis and toxin being the aggravating factors.Deificiency of the spleen and stomach is the initial factor of CAG,which influences the whole process of the disease.Qi stagnation,blood stasis and dampness retention are the triggering and aggravating factors for the ITT in CAG.The formation of blood stasis and toxin is the key to the progression and transition of CAG.Treatment of ITT in CAG should be based on the results of syndrome differentiation and gastroscopic findings by staging therapy.Before treatment,disease dianosis and syndrome differentiation should be made,and macro and micro syndrome differentiation should be carried out for assistance.Therapy of strengthening the spleen and supporting healthy qi should be implemented throughout the whole process of the disease.The early stage of CAG has the features of gastric mucosa with mild to moderate atrophy and with or without mild intestinal epithelial hyperplasia,the pathogenesis of early CAG is characterized by weakness of the spleen and stomach and is accompanied with the pathological factors of qi stagnation,damp-retention and blood stasis,and the basic treatment should adopt the therapies of strengthening the spleen and clearing heat,regulating qi and activating blood stasis.The advanced stage of CAG has the features of severe atrophic gastric mucosa with or without moderate to severe intestinal epithelial and/or mild to moderate intraepithelial neoplasia,the pathogenesis is characterized by weakness of the spleen and stomach,phlegm blended with blood stasis,and stasis-toxin in the gastric collaterals,and the basic treatment should adopt the therapies of supporting healthy qi and dissipating masses,and unblocking the collaterals and removing toxin,so as to construct an intact line to blocking the ITT in CAG with traditional Chinese medicine.
8.Transformer attention mechanism based three-dimensional dose prediction for lung cancer intensity-modulated radiotherapy
Yangting CHEN ; Xin YANG ; Fu JIN ; Bin FENG ; Wen LUO
Chinese Journal of Radiation Oncology 2024;33(6):532-539
Objective:To develop a deep learning architecture based on 3D Transformers to predict dose distribution within intensity modulated radiation therapy (IMRT) plans for lung cancer.Methods:Clinical data of 174 lung cancer patients treated with IMRT in Chongqing University Cancer Hospital between January 2020 and December 2022 were retrospectively analyzed. All patients were divided into the training ( n=116), validation ( n=29), and test ( n=29) sets. We employed the Swin Unet Transformer (Swin Unetr) model to predict the three-dimensional dose distribution. The model was trained using computed tomography (CT) images, planning target volume (PTV) images, organs at risk (OAR) images, beam configuration information images, and distance images. We used various evaluation metrics such as mean absolute errors (MAE), Dice similarity coefficients (DSC), and dose volume histogram (DVH) dosimetric parameters to assess the performance of Swin Unetr and compared it with three mainstream deep learning models: CGAN, ResSEUnet, and ResUnet. Results:The MAE of the dose distribution prediction by Swin Unetr was recorded at 0.0143±0.0055. Conversely, the values of CGAN, ResSEUnet, and ResUnet were 0.0162±0.0055, 0.0167±0.0063, and 0.0164±0.0057, respectively. Furthermore, Swin Unetr achieved the highest DSC values (>0.85) across all isodose volumes. Regarding DVH dosimetric parameters, excluding D 2% of PTV and D mean of the heart, Swin Unetr exhibited no statistically significant differences in the remaining DVH dosimetric parameters (all P>0.05), demonstrating the best evaluation results in 66.67% of the overall dosimetric parameters and 75% of the PTV dosimetric parameters. Conclusions:Swin Unetr achieves the best score in multiple dosimetric evaluation indicators, and the highest DSC across all isodose volumes. Swin Unetr has significantly improved the accuracy of three-dimensional dose prediction during IMRT for lung cancer.
9.Risk factors and survival of EBV-infected aplastic anemia patients after haploid allogeneic hematopoietic stem cell transplantation
Xin-He ZHANG ; Jia FENG ; Zheng-Wei TAN ; Yue-Chao ZHAO ; Hui-Jin HU ; Jun-Fa CHEN ; Li-Qiang WU ; Qing-Hong YU ; Di-Jiong WU ; Bao-Dong YE ; Wen-Bin LIU
Chinese Journal of Infection Control 2024;23(10):1228-1235
Objective To analyze the risk factors and survival status of Epstein-Barr virus(EBV)infection in pa-tients with aplastic anemia(AA)after haploid allogeneic hematopoietic stem cell transplantation(Haplo-HSCT).Methods Clinical data of 78 AA patients who underwent Haplo-HSCT in the hematology department of a hospital from January 1,2019 to October 31,2022 were analyzed retrospectively.The occurrence and onset time of EBV viremia,EBV-related diseases(EBV diseases),and post-transplant lymphoproliferative disorders(PTLD)were ob-served,risk factors and survival status were analyzed.Results Among the 78 patients,38 were males and 40 were females,with a median age of 33(9-56)years old;53 patients experienced EBV reactivation,with a total inci-dence of 67.9%,and the median time for EBV reactivation was 33(13,416)days after transplantation.Among pa-tients with EBV reactivation,49 cases(62.8%)were simple EBV viremia,2 cases(2.6%)were possible EBV di-seases,and 2 cases(2.6%)were already confirmed EBV diseases(PTLD).Univariate analysis showed that age 1<40 years old at the time of transplantation,umbilical cord blood infusion,occurrence of acute graft-versus-host disease(aGVHD)after transplantation,and concurrent cytomegalovirus(CMV)infection were independent risk fac-tors for EBV reactivation in AA patients after Haplo-HSCT.Multivariate analysis showed that concurrent CMV in-fection was an independent risk factor for EBV reactivation in A A patients after Haplo-HSCT(P=0.048).Ritu-ximab intervention before stem cell reinfusion was a factor affecting the duration of EBV reactivation(P<0.05).The mortality of EBV viremia,EBV diseases,and PTLD alone were 8.2%,50.0%,and 100%,respectively.The 2-year overall survival rate of patients with and without EBV reactivation were 85.3%,and 90.7%,respectively,difference was not statistically significant(P=0.897).However,patients treated with rituximab had 2-year lower survival rate than those who did not use it,with a statistically significant difference(P=0.046).Conclusion EBV reactivation is one of the serious complications in AA patients after Haplo-HSCT,which affects the prognosis and survival of patients.
10.Comparison of chemical components of Lonicera fragrantissima and Lonicera japonica based on LC-MS
Ying JIN ; Le-Wen XIONG ; Gao-Bin PU ; Fang ZHANG ; Jia LI ; Long-Fei ZHANG ; Yong-Qing ZHANG
Chinese Traditional Patent Medicine 2024;46(3):850-859
AIM To compare the components difference between Lonicera fragrantissima Lindl.et Paxt.(LFL)and Lonicerae japonicae Flos(LJF),and to evaluate the medicinal value of LFL,so as to provide reference for the development and utilization of LFL and LJF.METHODS With 70%methanol as extraction solvent,the components were analyzed by UPLC-TOF-MS,and the contents of 20 components were determined by HPLC-QQQ-MS.The components difference was determined by multivariate statistical analysis.RESULTS A total of 52 components were identified in the buds of LFL and LJF.There were 4 different components in LJF,and the contents of 20 quantitative components were significantly different.The contents of isochlorogenic acid C,ferulic acid,luteolin and rutin in the buds of LFL were more than 2 times that of LJF,and the contents of marchanic acid and marchanin were 11.96 times and 37.23 times that of LJF respectively.Maganin,isochlorogenic acid A,maganic acid,rutin and dicomachanic acid are the key differentiating components of LFL and LJF.CONCLUSION The buds of LFL and LJF have similar species,but the content difference is obvious.The buds of LFL have important medicinal value,which need further development and utilization.

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