1.Mechanisms of Tianma Goutengyin in Alleviating Neuronal Injury in Vascular Dementia Model Rats by Inhibiting A1 Astrocyte Activation via Regulating TNF-α/STAT3/α1ACT Signaling Pathway
Xiaoyan WANG ; Min ZHAO ; Feng TIAN ; Min XIAO ; Nan QU ; Fugui LIU ; Chixiao LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):56-65
ObjectiveTo investigate the effects of Tianma Goutengyin on the tumor necrosis factor-α (TNF-α)/signal transducer and activator of transcription 3 (STAT3)/α1-antichymotrypsin C-terminal tail fragment (α1ACT) signaling pathway and A1-type astrocytes in a rat model of vascular dementia. MethodsSeventy-two male Sprague-Dawley rats were randomly divided into six groups (n=12 per group): Sham-operated group, model group, Tianma Goutengyin high-, medium-, and low-dose groups (5.13, 10.26, and 20.52 g·kg-1), and a nimodipine group (8.1 mg·kg-1). The vascular dementia model was established by permanent bilateral common carotid artery occlusion, followed by 4 weeks of intervention. Learning and memory ability were evaluated using the novel object recognition test, and behavioral performance was assessed using the forced swimming test. Levels of interleukin-6 (IL-6) and C-C motif chemokine ligand 2 (CCL2) in hippocampal tissue were measured by enzyme-linked immunosorbent assay (ELISA). Hippocampal neuronal morphology was observed by Nissl staining, and apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Immunohistochemistry was used to detect positive expression of brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), and myelin basic protein (MBP). Western blot analysis was performed to measure the protein expression levels of TNF-α, TNF receptor 1 (TNFR1), phosphorylated STAT3 (p-STAT3), α1ACT, IL-6, complement component 3 (C3), BDNF, S100 calcium-binding protein A10 (S100A10), and GFAP in hippocampal tissue. ResultsCompared with the sham-operated group, the model group showed a significantly reduced relative recognition index in the novel object recognition test (P<0.01), prolonged immobility time and increased immobility frequency in the forced swimming test (P<0.01). Hippocampal IL-6 and CCL2 levels were significantly increased (P<0.01). Nissl staining revealed a marked reduction in neuronal number and loss of Nissl bodies (P<0.01). MBP-positive expression was significantly decreased (P<0.01), apoptosis was significantly increased (P<0.01), BDNF-positive expression was significantly reduced (P<0.05), and GFAP-positive expression was significantly increased (P<0.01). In addition, the protein expression levels of TNF-α, TNFR1, p-STAT3, α1ACT, IL-6, and C3 were significantly elevated (P<0.01), while BDNF and S100A10 expression levels were significantly decreased (P<0.01). Compared with the model group, all Tianma Gouteng yin dose groups exhibited a significant increase in the relative recognition index (P<0.05), shortened immobility time and reduced immobility frequency (P<0.05, P<0.01). IL-6 and CCL2 levels were significantly decreased (P<0.01), neuronal number was significantly increased (P<0.05, P<0.01), and MBP-positive expression was significantly enhanced (P<0.01). Apoptosis was significantly reduced (P<0.01), BDNF-positive expression was significantly increased (P<0.05), and GFAP-positive expression was significantly decreased (P<0.01). Moreover, the protein expression levels of TNF-α, TNFR1, p-STAT3, α1ACT, IL-6, and C3 were significantly decreased (P<0.01), while BDNF and S100A10 protein expression levels were significantly increased (P<0.01). ConclusionTianma Goutengyin may inhibit A1-type astrocyte activation in rats with vascular dementia through the TNF-α/STAT3/α1ACT signaling pathway, thereby reducing neuronal apoptosis and improving learning and memory function.
2.Material basis and action mechanism of drug-containing serum of Modified Erxian Pill inhibiting macrophage pyroptosis
Siyuan LI ; Yuru WANG ; Ye XU ; Di GUO ; Nan NAN ; Yang LIU ; Jie ZHAO ; Huiqin HAO
Chinese Journal of Tissue Engineering Research 2025;29(19):4029-4037
BACKGROUND:Our previous study found that Modified Erxian Pill could alleviate inflammation in collagen-induced arthritis rats,but its mechanism needs to be further verified. OBJECTIVE:To analyze the components absorbed in the blood of Modified Erxian Pill,and observe the effect of the drug-containing serum of Modified Erxian Pill on pyroptosis of J774A.1 macrophages. METHODS:(1)Analysis of components absorbed in the blood of Modified Erxian Pill:Ultra-high performance liquid chromatography-high resolution mass spectrometry was used to detect and identify Modified Erxian Pill and its components absorbed in the blood.(2)Effect of the drug-containing serum of Modified Erxian Pill on pyroptosis of J774A.1 macrophages:Molecular docking technology was used to initially verify the sesquiterpenoids and NLRP3 in components absorbed in the blood of Modified Erxian Pill.J774A.1 macrophages were randomly divided into blank control group,lipopolysaccharide+adenosine triphosphate group,and lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill with low(2.5%),medium(5%),and high(10%)dose groups.The release of lactate dehydrogenase in the cell supernatant of each group was detected according to the kit instructions.The levels of interleukin-1β and interleukin-18 in cell supernatant were detected in each group by ELISA.The cell membrane damage was detected by Hoechst/PI staining.The expression levels of NLRP3,Caspase-1,GSDMD,and GSDMD-N protein in the cells of each group were detected by western blot assay. RESULTS AND CONCLUSION:(1)A total of 32 active components of Modified Erxian Pill were identified,and 21 components entered the blood.The main components into blood included a variety of sesquiterpenoids.(2)Molecular docking results showed that 3-O-Acetyl-13-deoxyphomenone,Incensol oxide,Atractylenolide III,Rupestonic acid,and 3,7-Dihydroxy-9,11-eremophiladien-8-one had good binding activity with NLRP3.(3)Compared with the blank control group,lactate dehydrogenase activity and the expression levels of interleukin-1β and interleukin-18 were significantly increased in cell supernatant of lipopolysaccharide+adenosine triphosphate group(P<0.001).Hoechst/PI staining showed that the number of PI-positive cells was significantly increased.After the intervention of lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill group,all of them showed different degrees of reduction.(4)Compared with the blank control group,NLRP3,Caspase-1,GSDMD,and GSDMD-N protein expression levels were significantly increased in the lipopolysaccharide+adenosine triphosphate group(P<0.05).Compared with lipopolysaccharide+adenosine triphosphate group,the protein expressions of NLRP3,Caspase-1,GSDMD,and GSDMD-N were significantly decreased in the lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill group(P<0.05),and had a certain dose dependence.These findings verify that the drug-containing serum of Modified Erxian Pill may inhibit the pyroptosis of J774A.1 macrophages by regulating the NLRP3/Caspase-1/GSDMD pathway.
3.The relationship between multiple elements in urine and arsenic poisoning in populations exposed to drinking water arsenic in Inner Mongolia Autonomous Region
Yuchen GUO ; Binggan WEI ; Fan ZHAO ; Xinye LI ; Rui WANG ; Shuhui YIN ; Nan WU ; Lingling HE ; Zhen DI ; Kaiwen LIU ; Wei SONG ; Hui WANG ; Zhongbing ZHANG ; Danyu DENG ; Zhiwei GUO
Chinese Journal of Endemiology 2025;44(7):535-542
Objective:To study the relationship between the levels of multiple elements in urine and the risk of arsenic poisoning in populations exposed to drinking water arsenic in Inner Mongolia Autonomous Region (Inner Mongolia).Methods:From April 2023 to January 2024, a case-control study method was used to select 128 individuals with a residence time of ≥10 years in drinking water arsenic exposed areas in Inner Mongolia as study subjects. Eighty-one individuals diagnosed with arsenic poisoning were selected as the case group, and 47 healthy individuals were selected as the control group for urine sample collection and questionnaire survey. Inductively coupled plasma mass spectrometry was employed to determine the levels of 10 elements (chromium, manganese, cobalt, nickel, copper, zinc, arsenic, molybdenum, cadmium and lead) in urine. The levels of each element in urine were divided into four groups ( Q1, Q2, Q3, and Q4 groups) based on quartiles. The associations between the levels of various elements in urine and the risk of arsenic poisoning were studied using binary logistic regression model and restricted cubic spline (RCS). Results:The age of the control group and the case group [ M ( Q1, Q3)] were 61 (53, 69) and 61 (56, 67) years old, respectively. There were 19 and 43 males, and 28 and 38 females, respectively. There was no statistically significant differences in age and and gender composition between the two groups ( Z = - 0.39, P = 0.700; χ 2 = 1.91, P = 0.167). The levels of urinary copper and cadmium of the case group were higher than those of the control group, and the differences were statistically significant ( Z = - 2.66, - 2.16, P < 0.05). The results of univariate logistic regression analysis showed that urinary copper was an influencing factor for arsenic poisoning ( P = 0.017). The results of multivariate logistic regression analysis revealed that after adjusting for covariates, urinary copper and arsenic were independent influencing factors of arsenic poisoning ( P < 0.05). Taking Q1 group as a reference, urinary copper in Q3 group [ OR (95% CI) = 8.23 (1.81, 37.39), P = 0.006] increased the risk of arsenic poisoning, while urinary arsenic in Q2, Q3, and Q4 groups [ OR (95% CI) = 0.24 (0.06, 0.92), 0.12 (0.03, 0.53), 0.15 (0.04, 0.63), P < 0.05] decreased the risk of arsenic poisoning. After adjusting for covariates, RCS did not show a dose-response relationship between urinary copper, urinary arsenic, and arsenic poisoning ( P > 0.05). Conclusion:Urinary arsenic and copper are associated with the risk of arsenic poisoning in the drinking water arsenic exposed areas of Inner Mongolia, copper exposure may contribute significantly to arsenic poisoning.
4.Research Progress on the Application of Hot Melt Extrusion Technology in the Pharmaceutical Industry
Bing YANG ; Peng ZHAO ; Siyi SHUAI ; Xiaoxuan HONG ; Conghui LI ; Hui ZHANG ; Nan LIU ; Zengming WANG ; Jia WEN ; Aiping ZHENG
Herald of Medicine 2025;44(1):73-80
Hot melt extrusion(HME)technology employs thermodynamic and kinetic principles to mix pharmaceutical polymers with crystalline drugs at high temperatures and extrude them,embedding drug molecules within the polymer matrix to form solid dispersions.Due to its solvent-free nature,capability for one-step processing,and support for continuous operation,HME has garnered significant attention in the pharmaceutical industry in recent years.This article introduced the basic principles and development history of HME technology and its marketed drugs.It reviewed the research progress of HME technology in improving drug solubility,masking taste,controlled release,targeted release,oral dispersible films,implant formulations,semi-solid formulations,and 3D printed formulations.Additionally,the article summarized the advantages and limitations of HME technology and provided an outlook on its future development.
5.Targeted screening and profiling of massive components of colistimethate sodium by two-dimensional-liquid chromatography-mass spectrometry based on self-constructed compound database
Xuan LI ; Minwen HUANG ; Yue-Mei ZHAO ; Wenxin LIU ; Nan HU ; Jie ZHOU ; Zi-Yi WANG ; Sheng TANG ; Jian-Bin PAN ; Kee-Lee HIAN ; Yao-Zuo YUAN ; Taijun HANG ; Hai-Wei SHI ; Hongyuan CHEN
Journal of Pharmaceutical Analysis 2025;15(2):401-410
In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics.Similarities and variations of components present significant analytical challenges.A two-dimensional(2D)liquid chromatography-mass spectrometry(LC-MS)method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium(CMS).A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated.For efficient and high-accuracy screening of CMS,a targeted method based on a self-constructed high resolution(HR)mass spectrum database of CMS components was established.The database was built based on the commercial MassHunter Personal Compound Database and Library(PCDL)software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening.On this basis,the unknown peaks in the CMS chromatograms were deduced and assigned.The molecular formula,group composition,and origins of a total of 99 compounds,of which the combined area percentage accounted for more than 95%of CMS components,were deduced by this 2D-LC-MS method combined with the MassHunter PCDL.This profiling method was highly efficient and could distinguish hundreds of components within 3 h,providing reliable results for quality control of this kind of complex drugs.
6.Research progress in laboratory artificial breeding technologies for ticks
Xiao-nan DONG ; Lian-yang SUN ; Hao CUI ; Jia-mei KANG ; Yu-lin DING ; Yong-hong LIU ; Li ZHAO
Chinese Journal of Zoonoses 2025;41(1):67-74
As the world's second largest vector of pathogens,ticks can spread a variety of pathogens by sucking the host's blood.Ticks not only threaten human life and health,but also cause great economic losses in animal husbandry.Artificial breeding of ticks can provide a stable environment for the growth and reproduction of ticks,thereby generating sufficient exper-imental materials for understanding ticks'biological characteristics,studying tick-borne pathogens,and developing anti-tick drugs and vaccines.Current methods of breeding ticks in the laboratory can be roughly divided into two categories:breeding methods using host animals or artificial membranes.The selection of breeding method must be comprehensively considered,ac-cording to tick types,blood-sucking habits,living environments,and other aspects.The development processes of the two methods,and their respective advantages and disadvantages,are described and discussed,to assist laboratories in artificial breeding of ticks.
7.Extraction and culture of enteric glial cells from C57BL/6 newborn neonatal mice
Nan ZHAO ; Yong DING ; Hang XIU ; Pengfei LIU ; Guogang LIANG
Chinese Journal of Tissue Engineering Research 2025;29(31):6656-6660
BACKGROUND:The pathogenesis of inflammatory bowel disease involves inflammation,immune activation,visceral hypersensitivity,and dysbiosis of the gut microbiota.Inflammation promotes the release of inflammatory mediators by immune cells,damaging the enteric nervous system.Enteric glial cells are an important component of the intestinal nervous system and are excellent cells for studying intestinal neuroinflammation.Primary enteric glial cells play a crucial role in exploring cell therapies for intestinal nervous system diseases.Currently,the methods for obtaining these cells are mostly cumbersome.Therefore,finding a convenient and fast method for extracting this cell is crucial.OBJECTIVE:To establish a method for optimizing the isolation,culture,and identification of mouse enteric glial cells.METHODS:0-7-day-old C57BL/6 neonatal mice were euthanized by excessive inhalation of isoflurane.After soaking in 75%alcohol for disinfection,the duodenum(1 cm below the pylorus to 1 cm above the Qu's ligament)was removed by laparotomy at the midline of the abdomen.A 1 mL syringe was filled with DPBS and the intestinal contents were repeatedly rinsed until the intestine became translucent,and the mesentery and blood vessels were peeled off.The duodenum was cut to a size of 1 mm and digested in 0.25%EDTA trypsin for 20 minutes.Then an equal amount of DMEM/F12 complete culture medium was added to terminate digestion.The liquid was filtered through a 100 μm cell filter,centrifuged,and the cells were resuspended in 1 mL of DMEM/F12 complete culture medium.When the cell adhesion growth density reached 80%,cells were digested for subculture.When cells were cultured to the third generation,glial fibrillary acid protein labeled with enteric glial cells was used for identification by immunofluorescence method.RESULTS AND CONCLUSION:The isolated and cultured cells were full of colloids,with protrusions extending outward and passable.Glial fibrillary acid protein staining was positive.This method can successfully isolate and culture enteric glial cells and is easy to operate,providing a stable model for the study of the pathophysiology of the enteric nervous system.
8.Review of application scope of mobile medical devices combined with EMA method for lung cancer patient caring
Zi-dan WANG ; Hong-yue WU ; Bing LI ; Xin-tong ZHENG ; Jun-ling LIU ; Ying-nan ZHAO ; Yan LI
Chinese Medical Equipment Journal 2025;46(10):71-77
Relevant literature on mobile medical devices combined with the ecological momentary assessment(EMA)method applied to lung cancer patient caring was collected from some databases of CNKI,Wanfang,VIP,China Biomedical Literature Database,PubMed,Embase,Cochrane Library,CINAHL and Web of Science.The method of scoping review was used to sort out the general characteristics of the included literature,types and application of mobile medical devices,assessment content elements and outcome indicators.The feasibility and validity of mobile medical devices combined with the EMA method for the symptom assessment of lung cancer patients were described,whose advantages in monitoring during lung cancer caring and application prospects were elaborated.The problems of mobile medical devices during practical application were pointed out and some countermeasures were put forward accordingly.References were provided for personalized remote caring of lung cancer patients and development of intelligent multi-modal mobile devices.[Chinese Medical Equipment Journal,2025,46(10):71-77]
9.Acute extensive anterior myocardial infarction after medullary infarction:a case report
Pei-xun HE ; Yan-ming LIU ; Yi SUN ; Peng WU ; Lan WANG ; Xue-yong LI ; Jun-jie YANG ; Wei-nan ZHAO
Chinese Journal of Interventional Cardiology 2025;33(9):536-540
The medulla oblongata,situated at the caudal portion of the brainstem,serves as a critical regulatory center responsible for maintaining fundamental vital functions including respiratory and cardiovascular homeostasis.As a pivotal hub within the autonomic nervous system,it orchestrates the coordinated control of afferent and efferent neural pathways.Dysfunction of this region may precipitate life-threatening cardiorespiratory arrest,associated with substantial mortality rates.This case report presents a patient who developed acute extensive anterior myocardial infarction during treatment with dual antiplatelet therapy and moderate-intensity statins following acute medullary infarction.It is hypothesized that the pathogenesis may involve the acceleration of plaque erosion by the stroke-heart syndrome.This clinical case provides valuable insights into the complex neurocardiac interplay,particularly highlighting the imperative for enhanced recognition of brain-heart axis interactions in cerebrovascular pathology.
10.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.

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