1.Mechanism of Shaoyaotang in Modulating MDSCs-related Immunosuppressive Microenvironment in Prevention and Treatment of Colitis-associated Carcinogenesis
Xue CHEN ; Chenglei WANG ; Bingwei YANG ; Haoyu ZHAI ; Ying WU ; Weidong LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):10-19
ObjectiveTo explore the mechanism of Shaoyaotang in the prevention and treatment of colitis-associated carcinogenesis (CAC) based on myeloid-derived suppressor cells (MDSCs)-related immunosuppressive microenvironment. MethodsA total of 140 six-week-old SPF FVB male mice were randomly divided into seven groups: Blank group, Shaoyaotang without model group (7.12 g·kg-1), model group, sulfasalazine group (0.52 g·kg-1), Shaoyaotang low-dose group (3.56 g·kg-1), Shaoyaotang medium-dose group (7.12 g·kg-1) and Shaoyaotang high-dose group (14.24 g·kg-1), with 20 mice in each group. The blank control group and the Shaoyaotang without model group received a single intraperitoneal injection of physiological saline (10 mg·kg-1), while the other five groups were given a single intraperitoneal injection of azoxymethane (AOM) (10 mg·kg-1). After 1 week, the mice were given drinking water containing 2% dextran sulfate sodium (DSS) for 1 week, followed by normal drinking water for 2 weeks. This cycle was repeated three times over a total period of 14 weeks to establish the CAC mouse model. Each group was administered gavage once daily for 2 weeks starting on the 14th day of the experiment, followed by three times a week until the end of the experiment. The body weight of the mice was recorded weekly. Mice were sacrificed on the 28th and 98th days of the experiment. After dissection, the colon length, colon weight, spleen weight, tumor size, and tumor number were measured. Hematoxylin and eosin (HE) staining was used to assess the pathological morphology of colon tumor tissue. Flow cytometry was used to detect MDSCs, regulatory T cells (Tregs), CD4+ T cells, CD8+ T cells, and the CD4+/CD8+ T cell ratio in the spleen. Immunohistochemistry was used to detect the expression levels of programmed cell death protein-1 (PD-1), programmed cell death ligand 1 (PD-L1), phosphorylated AMP-activated protein kinase (p-AMPK), phosphorylated nuclear factor-κB (p-NF-κB), and hypoxia-inducible factor 1α (HIF-1α) in the colon tissue. ResultsOn day 14, compared with the blank group, the body weight of the model group was significantly reduced (P<0.01), reaching its lowest point on day 28 (23.39 ± 0.95 ) g. On days 28 and 98, compared with the blank group, the colon length in the model group was significantly shortened (P<0.01), the colon index significantly increased (P<0.01), the spleen index significantly increased (P<0.01), and the tumor load significantly increased (P<0.01). HE staining showed that in the model group, tumor cells, a large number of inflammatory cell infiltrates, goblet cell disappearance, and crypt loss were observed. In each dose group of Shaoyaotang, the damage to the colonic mucosa, inflammatory cell infiltration, and crypt structure destruction were alleviated. Compared with the model group, the body weight of mice in each dose group of Shaoyaotang increased. On day 98, the colon length was significantly increased (P<0.01), the colon index significantly decreased (P<0.01), the spleen index significantly decreased (P<0.01), and the tumor burden significantly decreased (P<0.01) in each Shaoyaotang dose group. On days 28 and 98, MDSCs and Tregs in the spleen of the medium- and high-dose Shaoyaotang groups were significantly reduced (P<0.01), while CD4+ T cells and the CD4+/CD8+ T cell ratio were significantly increased (P<0.01). The proportion of CD8+ T cells in the spleen and the expression levels of PD-1 and PD-L1 in the colon tissues of mice in each Shaoyaotang dose group were significantly increased to varying degrees (P<0.05, P<0.01). On days 28 and 98, the expression of p-AMPK-positive cells in the colon tissue of the medium- and high-dose Shaoyaotang groups was significantly increased (P<0.01), while the expression of p-NF-κB and HIF-1α was significantly reduced (P<0.01). ConclusionShaoyaotang can regulate MDSC recruitment and modulate the immune function of T lymphocyte subsets to inhibit the occurrence and development of AOM/DSS-induced CAC in mice. The mechanism may be related to the activation of the AMPK/NF-κB/HIF-1α pathway.
2.Effect of Huanglian Jiedutang in Regulating Ferroptosis in Mice with Atherosclerosis Based on Nrf2/GPX4 Signaling Pathway
Zhaohui GONG ; Li GAO ; Huiqi ZHAI ; Jinzi YU ; Qingmin CHU ; Chuanjin LUO ; Lijin QING ; Wei WU ; Rong LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):22-28
ObjectiveTo study the mechanism of Huanglian Jiedutang (HLJDT) in treating mice with atherosclerosis (AS) by improving ferroptosis. MethodsA total of 10 SPF C57BL/6J mice were selected as a normal group, and 50 ApoE-/- mice were randomly divided into five groups: model group, low-dose group of HLJDT, medium-dose group of HLJDT, high-dose group of HLJDT, and atorvastatin (ATV) group. ApoE-/- mice were fed a high-fat diet for eight weeks to establish the AS model, and at the 9th week, they were given normal saline, low, medium, and high doses of HLJDT (3.9, 7.8, 15.6 g·kg-1·d-1), and atorvastatin calcium tablets (0.01 g·kg-1·d-1), respectively, for a total of eight weeks. The formation of aortic plaque in mice was observed by gross oil red O staining and Masson staining. The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) in blood fat were measured by the automatic biochemical analyzer, and the mitochondrial structure of the aorta was observed by transmission electron microscopy. The content of serum superoxide dismutase (SOD) in serum was detected by enzyme-linked immunosorbent assay (ELISA). The content of reduced glutathione (GSH) in serum was detected by the microplate method, and that of malondialdehyde (MDA) in serum was detected by the TBA method. The protein expression of nuclear factor E2-associated factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling pathway was detected by Western blot. ResultsCompared with those of the normal group, the contents of TC, LDL-C, TG, HDL-C, and MDA in the serum and the aortic vascular plaque deposition of the model group were significantly increased (P<0.01), while the expression levels of SOD and GSH in serum, as well as Nrf2, solute carrier family 7 member 11 (SLC7A11), and GPX4 in aorta were significantly decreased (P<0.01). Mice in the model group appeared mitochondrial fragmentation and vacuolation in the aorta, volume atrophy, mitochondrial crista reduction, or a loose and disorganized form. Compared with those in the model group, the aortic vascular plaque deposition was significantly decreased in the low-dose, medium-dose, and high-dose groups of HLJDT and ATV group, and the contents of serum TC, LDL-C, TG, and MDA in serum were significantly decreased (P<0.05, P<0.01). The contents of serum SOD and GSH and the expression levels of Nrf2, SLC7A11, and GPX4 in the aorta were increased (P<0.05, P<0.01), and the symptoms of aortic mitochondrial vacuolation were alleviated. The number of cristae was increased, and they were ordered neatly. ConclusionHLJDT can reduce aortic vascular plaque deposition, decrease blood lipid and MDA expression, increase SOD and GSH expression, and ameliorate the pathological changes of ferroptosis, the mechanism of which is related to the Nrf2/GPX4 signaling pathway.
3.Analysis of Animal Models of Allergic Asthma Based on Data Mining
Han WU ; Zhixiang HU ; Meiqi JI ; Hao YIN ; Yu'e LYU ; Chuntao ZHAI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):211-217
ObjectiveTo provide a basis for the establishment of an ideal animal model of allergic asthma by statistically analyzing the modeling characteristics and the selection of indicators of the available models. MethodsWe retrieved the relevant articles from China National Knowledge Infrastructure(CNKI), VIP, Wanfang Data, SinoMed, and PubMed with "allergic asthma" as the keyword and the time interval from January 2019 to January 2024. Through integrating the literature and extracting data, we used Excel 2021 to create a personal database and sorted out the animal strains, genders, allergenic substances, modeling routes, and test indicators and methods. Excel 2021, Cytoscape 3.10.2, and SPSS Modeler 18.0 were then used to analyze the relevant characteristics of the animal models. ResultsA total of 418 articles were included in the database, and the comparative analysis showed that the most frequently used animal strain for modeling was BALB/c mice, and female animals were mostly used. The main modeling method was sensitization by intraperitoneal injection of ovalbumin (OVA), which was combined with intranasal inhalation. The test indicators mainly included appearance signs, cellular analysis, lung histopathology, lung function indicators, and protein and gene expression in the lung. The test methods mainly involved pathological staining, enzyme-linked immunosorbent assay, immunohistochemistry, immunofluorescence, Western blot, and polymerase chain reaction(PCR) assays. ConclusionThere is no recognized modeling method or evaluation standard for the animal models of allergic asthma. Based on the results of data analysis, the OVA-induced allergic asthma model in BALB/c mice is recommended. The main criteria for evaluating the success of modeling are the general behavioral changes, the morphological changes of the airway and inflammatory cell infiltration in the lung tissue, the changes of pro-inflammatory and anti-inflammatory cytokines in the serum, and the alterations of inflammatory cells in the bronchoalveolar lavage fluid.
4.Analysis of ancient medical physicians′ spatial theory from the perspective of liver and mingmen visceral manifestation
Chongcheng XI ; Jie ZHANG ; Wenjun WU ; Zhiwen ZHANG ; Shuangqing ZHAI ; Quansheng FENG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(2):187-192
Yin-yang, visceral manifestation, and ti-yong theories are the core theories of traditional Chinese medicine (TCM) and play a crucial role in its formation and development. With the continuous evolution of Chinese philosophy, TCM philosophy and theories have undergone significant influence, resulting in differing interpretations of the visceral manifestation of liver and mingmen across various historical periods by different medical practitioners. This paper focuses on the different understandings of the position of liver and mingmen, combining relevant philosophical images and TCM anatomical illustrations to deeply explore ancient medical theorists′ concepts regarding the four spatial directions of left, right, up, and down. The research reveals that ancient medical theorists′ conceptualization of spatial theory transitioned from an initial circular motion to a vertical movement, with the focus shifting from the upper part to the lower part. The primary reasons for these differences and changes could be explained by the varying emphasis on the ti-yong theory and differing focal points within the yin-yang theory. This study systematically examines the evolution of visceral manifestation theories related to liver and mingmen, highlights the shifts in physicians′ perspectives on spatial theory, and analyzes the influence of the ti-yong theory and yin-yang theory on these changes. The findings aim to provide a theoretical guide for advancing research and clinical application of spatial theory in TCM, thereby fostering the integration of TCM philosophy with medical theory.
5.Exploration on the Syndrome Differentiation and Treatment Strategies for Inflammation-Cancer Transformation in Inflammatory Bowel Disease Based on the Theory of Cold Qi-Induced Accumulation
Jiahe WU ; Muyao CUI ; Xue CHEN ; Bingwei YANG ; Haoyu ZHAI ; Chenglei WANG ; Ying WU ; Weidong LI
Journal of Traditional Chinese Medicine 2025;66(14):1489-1494
It is proposed that cold qi-induced accumulation encapsulates the core pathogenesis of the inflammation-cancer transformation in inflammatory bowel disease (IBD). Cold pathogens may serve as the initiating factor. When first invading the intestines, cold pathogens obstruct the flow of qi; over time, the lingering cold impairs the middle jiao (焦), eventually leading to the accumulation of cold-phlegm and blood stasis. Based on the progressive nature of this transformation, the process can be divided into three stages, active stage, remission stage, and carcinogenic stage. In the active stage, the main pathogenesis involves stagnation of cold qi and accumulation of damp-heat in the intestines; in the remission stage, cold qi impairs the spleen, disrupting its transport and transformation functions; and in the carcinogenic stage, the mechanisms include cold-induced accumulation, phlegm accumulation from cold, and stagnation of cold and blood stasis. Accordingly, the treatment strategies are proposed.In the active stage, regulating qi, relieving stagnation, and harmonizing cold and heat; in the remission stage, warming yang, dispersing cold, tonifying qi, and strengthening the spleen; and in the carcinogenic stage, promoting qi circulation, dispersing cold, resolving phlegm, activating yang, and eliminating stasis to remove accumulation. These approaches aim to interrupt the transformation of IBD into colorectal cancer.
6.Progress of the effect of hydroxyacyl-coenzyme A dehydrogenase in cancer development and its mechanism
Guojia WU ; Shujie ZHAI ; Xiao SUN ; Yiran HUANG ; Yongmei LI ; Li SUN
Basic & Clinical Medicine 2024;44(1):119-123
A close relationship between fatty acid metabolism and cancer development is well-established.The hydroxyacyl-coenzyme a dehydrogenase(HADH),a key enzyme in fatty acid beta-oxidation,has recently been identified as an anti-oncogenic factor in various cancers and an oncogenic factor in conditions like acute myeloid leukemia.In cancer cells,HADH not only directly catalyzes fatty acid beta-oxidation but also indirectly influences multiple signaling pathways such as PPAR,TNF-α,JAK-STAT3,PI3K/Akt,IFN-γ,MAPK,and non-canonical Wnt signaling pathways,affecting cancer cell proliferation and migration.HADH shows promise as a potential tumor biomarker for diagnosis,treatment,and prognosis in different cancer types,holding significant clinical value.
7.Study on the potential allergen and mechanism of pseudo-allergic reactions induced by combined using of Reduning injection and penicillin G injection based on metabolomics and bioinformatics
Yu-long CHEN ; You ZHAI ; Xiao-yan WANG ; Wei-xia LI ; Hui ZHANG ; Ya-li WU ; Liu-qing YANG ; Xiao-fei CHEN ; Shu-qi ZHANG ; Lu NIU ; Ke-ran FENG ; Kun LI ; Jin-fa TANG ; Ming-liang ZHANG
Acta Pharmaceutica Sinica 2024;59(2):382-394
Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and
8.Feasibility study of low tube voltage and low contrast medium combined with IMR technology in 3DCTA of vertebral artery V3 segment
Junlin YANG ; Duchang ZHAI ; Xiuzhi ZHOU ; Rong LIU ; Guohua FAN ; Wu CAI
Chongqing Medicine 2024;53(1):5-10
Objective To investigate the feasibility of low-voltage,automatic tube current adjustment(ATCM)and low contrast agent concentration,dose and injection rate combined with full-model iterative re-construction(IMR)in vertebral artery V3-segment three-dimensional CT angiography(3DCTA).Methods A total of 60 patients with suspected upper cervical spine,craniocervical junction lesions undergoing cervical vertebral artery V3 segment 3DCTA in this hospital from November 2019 to May 2020 were selected and divided into the group A and B by adopting the random number table method,30 cases in each group.The group A adopted the ATCM technology of 80 kV,average tube current of 50 mAs,25 mL of contrast agent io-hexol(iodine content 300 mg/mL)combined IMR technology with an injection rate of 3 mL/s,while the group B adopted 120 kV,150 mAs fixed tube current,50 mL injection rate of 5 mL/s contrast agent iopamidol(iodine content 370 mg/mL)combined filter back projection(FBP)reconstruction technology.CT value,noise,signal-to-noise ratio(SNR),contrast noise ratio(CNR)and image sensitivity(FOM)were measured and compared between the two groups and the quality of the resulting images was evaluated.The CT volumet-ric dose index(CTDIvol)and dose-length product(DLP)were recorded,and the effective dose(ED)was cal-culated.Results There was no statistically significant difference in the vertebral arterial CT value between the two groups(P>0.05),but the noise of the group A was lower than that of the group B(P<0.05),SNR,CNR and FOM of the group A were greater than those of the group B(P<0.05).The image quality of the two groups met the requirements of clinical diagnosis[(4.78±0.41)points vs.(4.85±0.35)points],and there was no statistically significant difference in the subjective evaluation of image quality(P>0.05).The CTDIvol,DLP and ED levels in the group A were lower than those in the group B(P<0.05).The iodine in-takes of contrast medium in the group A and group B were 7.5 g and 18.5 g,respectively,and the iodine flow rates of contrast agent were 0.9 and 1.85 mg/s,respectively,and compared with group B,the iodine intake and iodine flow rate of the group A were decreased by 59.5%and 51.4%,respectively.Conclusion Low tube voltage ATCM and low contrast concentration,dose and injection rate combined with IMR technology can not only ensure the 3DCTA image quality of vertebral artery V3 segment,but also reduce the radiation dose re-ceived by the patients,and reduce the iodine intake and iodine flow rate of contrast agent.
9.Brain white matter variation in patients with obstructive sleep apnea-hypopnea syndrome with diffusional kurtosis imaging
Yaoyao ZHAI ; Xiaoxia LIU ; Chan MENG ; Shuhua LI ; Dahai WU
Chinese Archives of Otolaryngology-Head and Neck Surgery 2024;31(1):49-53
OBJECTIVE To explore the changes of brain white matter of the patients with obstructive sleep apnea-hypopnea syndrome(OSAHS)with magnetic resonance diffusional kurtosis imaing(DKI).METHODS There were 38 patients with OSAHS examined by polysomnogram(PSG)from November 2017 to June 2021,and 32 non-OSAHS controls matched in gender and age who were included in this study.All the subjects were scanned by DKI.The different encephalic regions through comparing kurtosis fractional anisotropy(KFA)values of all encephalic regions between the two groups were found,and the relationship between the KFA values of the different encephalic regions in OSAHS patients and the apnea-hypopnea index(AHI),lowest saturation oxygen(LSaO2)and the percent of the total record time spent below 90%oxygen saturation(TS90%)in PSG were analyzed.RESULTS The KFA values of white matter fiber tracts in corpus callosum,bilateral corona radiata,cingulate gyrus,right superior cerebellar peduncle and inferior cerebellar peduncle of OSAHS group were obviously lower than control group(P<0.05).After controlling for age and body mass index(BMI),the partial correlation between AHI and the KFA values of corpus callosum,left posterior corona radiata,right anterior corona radiata,cingulate gyrus in OSAHS group were also negative(r=-0.344,-0.380,-0.406,-0.53,P<0.05).The partial correlation between LSaO2 and the KFA values of corpus callosum,left posterior corona radiata,right anterior corona radiata,cingulate gyrus,right superior cerebellar peduncle in OSAHS group were also positive(r=0.366,0.406,0.446,0.404,0.342,P<0.05).The partial correlation between TS90%and the KFA values of corpus callosum,left posterior corona radiata,right anterior corona radiata,cingulate gyrus,right superior cerebellar peduncle and inferior cerebellar peduncle in OSAHS group were also negative(r=-0.414,-0.352,-0.355,-0.336,-0.456,-0.360,P<0.05).CONCLUSION Recurrent apnea and hypoxemia at night of OSAHS patients can cause damage to white matter fibers in parts of encephalic regions.
10.Exposure-response relationship between air pollutants, temperature, and risk of hospital admission for type 2 diabetes mellitus
Fei ZHAI ; Naipeng LIU ; Shenshen WU ; Jiajia WANG
Journal of Environmental and Occupational Medicine 2024;41(10):1109-1114
Background The population with diabetes in China is increasing year by year. Current research has found that either air pollution or temperature has an impact on the occurrence and development of diabetes, but the interaction between the two is unclear yet. Objective To investigate the effects and the lag effects of air pollutants and temperature on the risk of hospital admission for type 2 diabetes in Hefei, Anhui Province from 2016 to 2019, as well as to verify potential interaction between air pollutants and temperature. Methods This study collected hospital admission data for patients with type 2 diabetes from a tertiary hospital in Hefei, Anhui Province, and the corresponding monitoring data on air pollutants and meteorological factors from 2016 to 2019. Firstly, a distributed lag non-linear model (DLNM) was used to explore the effects of air pollutants and temperature on the risk of hospital admission for type 2 diabetes. Subsequently, a bivariate response surface model was used to explore potential interaction between temperature and various pollutants on frequency of hospital admission due to diabetes. Temperature was further divided into lower, medium, and higher levels by percentiles during the study period, and the potential interaction between air pollutants and temperature strata were verified . Results After controlling long-term trend, seasonal trend, holiday effect, and day of the week effect, the results of single pollutant models showed that for every 10 μg·m−3 increase in fine particulate matter (PM2.5), inhalable particulate matter (PM10), and nitrogen dioxide (NO2), the relative risk (RR) values for hospital admission due to type 2 diabetes were 1.032 (95%CI: 1.021, 1.043), 1.018 (95%CI: 1.008, 1.026), and 1.037 (95%CI: 1.016, 1.058), respectively; for every 1 mg·m−3 increase in carbon monoxide (CO), the RR value for hospital admission due to type 2 diabetes was 1.319 (95%CI: 1.163, 1.495); the increases in sulfur dioxide (SO2), ozone (O3), and daily average temperature showed no statistically significant impact on hospital admission due to type 2 diabetes. The results of bivariate response surface models suggested that daily average temperature and various pollutant levels spontaneously affected the risk of hospital admission for type 2 diabetes, but the stratified analysis did not find significant differences in the effect of PM2.5 on the risk of hospital admission due to type 2 diabetes across different temperature strata. Conclusion Increases in the concentrations of PM2.5, PM10, NO2, and CO elevate the risk of hospital admission for type 2 diabetes. This study could not confirm the interactions between daily average temperature and various pollutants.


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