1.Theoretical research on LOU Ying′s guideline and item syndrome differentiation
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):483-489
The guideline and item classification approach represents a distinct historical method ology, first introduced by ZHU Xi in his Compendium of Comprehensive Mirror for Aid in Government during the Southern Song Dynasty. LOU Ying later adapted this framework to the field of traditional Chinese medicine, critically analyzing and addressing the limitations of prior academic theories. By drawing upon the rich intellectual traditions of classical texts and historical works, LOU Ying restructured and refined his ideas, ultimately establishing the "guideline and item" medical theory. This innovative framework profoundly influenced LOU Ying′s work, shaping both the compilation of medical texts and the development of novel theoretical approaches in traditional Chinese medicine. In disease differentiation and treatment, LOU Ying proposed the theory of guideline and item classification, that is, taking yin and yang as two guidelines, taking qi and blood, exterior and interior, upper and lower parts, deficiency and excess, cold and heat as ten items, and constructing a syndrome differentiation system focusing on qi and blood, focusing solely on upper and lower parts, distinguishing exterior and interior, carefully examining deficiency and excess, and distinguishing cold and heat. The guideline and item classification system integrates and harmonizes multiple syndrome differentiation method ologies, including the eight-principle pattern identification, viscera syndrome differentiation, differentiation of syndromes according to the pathogenesis of Sanjiao, and qi-blood-fluid pattern identification. As a precursor to modern method of syndrome differentiation and treatment, it possesses unique theoretical significance and considerable clinical relevance. Its applicability to diagnosing and treating various diseases, coupled with its greater operational practicality compared to other methods, highlights its value in contemporary clinical practice. This system offers a complementary and enhanced framework for syndrome differentiation and treatment, warranting further adoption and promotion in the clinical setting.
2.Percutaneous coronary intervention vs . medical therapy in patients on dialysis with coronary artery disease in China.
Enmin XIE ; Yaxin WU ; Zixiang YE ; Yong HE ; Hesong ZENG ; Jianfang LUO ; Mulei CHEN ; Wenyue PANG ; Yanmin XU ; Chuanyu GAO ; Xiaogang GUO ; Lin CAI ; Qingwei JI ; Yining YANG ; Di WU ; Yiqiang YUAN ; Jing WAN ; Yuliang MA ; Jun ZHANG ; Zhimin DU ; Qing YANG ; Jinsong CHENG ; Chunhua DING ; Xiang MA ; Chunlin YIN ; Zeyuan FAN ; Qiang TANG ; Yue LI ; Lihua SUN ; Chengzhi LU ; Jufang CHI ; Zhuhua YAO ; Yanxiang GAO ; Changan YU ; Jingyi REN ; Jingang ZHENG
Chinese Medical Journal 2025;138(3):301-310
BACKGROUND:
The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China.
METHODS:
This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences.
RESULTS:
Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n = 278] vs . 43.7% [ n = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses.
CONCLUSION
This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans
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Percutaneous Coronary Intervention/methods*
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Male
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Female
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Coronary Artery Disease/drug therapy*
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Retrospective Studies
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Renal Dialysis/methods*
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Middle Aged
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Aged
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China
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Proportional Hazards Models
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Treatment Outcome
3.Comparative Evaluation of Detection Performance of Four Blood Culture Systems for Common Pathogens and Antibiotic Absorption Capacity in Clinical Laboratory
Yahua RAO ; Min JIA ; Yongtao WANG ; Zhimin HU ; Jiajia GAO
Journal of Modern Laboratory Medicine 2024;39(5):199-204
Objective To evaluate the detection performance of common strains and the antimicrobial binding capacity of four blood culture systems made by BMX-FA/N Plus,Zhengzhou Anto,Zhuhai DIER and Chongqing Zhongyuan.Methods According to the common pathogens of clinical bloodstream infections in Wuhan No.1 Hospital,ATCC standard isolates of Staphylococcus aureus,Streptococcus pneumoniae,Enterococcus faecalis,Escherichia coli,Pseudomonas aeruginosa,Haemophilus influenzae,Stenotrophomonas Maltophil,Bacteroides tenuis and Candida glabla were chosen to explore.Prefabricated bacterial suspension and sterile horse blood were injected into different brands of blood culture systems to simulate the blood samples of patients with non-antibiotic treatment and antibiotic treatment.Six commonly used clinical antibiotics,Imipenem,Piperacillin/Tazobactam,Cefoperazone/Sulbactam,Levofloxacin,Vancomycin and Micafungine,were added to the blood samples after simulated antibiotic treatment.The performance was evaluated by recording the positive bottles and the detection time of each brand culture systems within five days with and without antibiotic.Results In the absence of antibiotic,four blood culture systems showed 100%recovery on all of the pathogens.Staphylococcus aureus,Pseudomonas aeruginosa and Haemophilus influenzae were recovered earlier in DIER aerobic bottles than BMX-FA Plus aerobic bottles,and the differences were statistically significant(t=2.608,5.547,12.247,all P<0.05).The time to detection of Staphylococcus aureus,Streptococcus pneumoniae,Enterococcus faecalis and Haemophilus influenzae in Zhongyuan anaerobic bottles was significantly faster than that of BMX-FA Plus anaerobic bottles,with an average shortening of 1.92~10.80 h,and the differences were statistically significant(t=30.187,5.367,33.068,24.855,all P<0.05).When antibiotics added,BMX-FA Plus culture bottle showed 100%recovery to all the detecting pathogens with the peak concentration antibiotics except Cefoperazone/Sulbactam,while the recovery in Zhongyuan blood culture bottle also was 100%with peak concentration antibiotics of Piperacillin/Tazobactam,Levofloxacin and Micafunzin.The peak concentration of imipenem antibiotics in domestic bottles was only detected in Anto anaerobic bottles,with lower positive detection rate(66.7%)lower than that of BMX-FA Plus(100%)and a later detection,and the difference was statistically significant(t=-21.000,P=0.030).Conclusion In the absence of antibiotic interference,the positive detection rate of the above pathogens are the same for four blood culture systems,and the time to detection of DIER and Zhongyuan systems is shorter than that of BMX-FA/N Plus.In the presence of antibiotic interference,the detection ability to pathogens in BMX-FA/N Plus system is the best,followed by domestic Zhongyuan system.
4.Mechanism of Buzhong Yiqitang Intervening in Pyroptosis of AIT in NOD.H-2h4 Mice Based on NLRP3/Caspase-1/GSDMD Pathway
Zhimin WANG ; Xiao YANG ; Yiran CHEN ; Ziyu LIU ; Qingyang LIU ; Chenghan GAO ; Chen WANG ; Tianshu GAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(12):8-15
ObjectiveTo explore the mechanism of Buzhong Yiqitang on pyroptosis in autoimmune thyroiditis (AIT) mice based on the NOD-like receptor hot protein domain related protein 3 (NLRP3)/cysteinyl aspartate specific proteinase-1(Caspase-1)/Gasdermin D (GSDMD) pathway. MethodSixty NOD.H-2h4 mice were divided into normal group, model group, low, medium, and high dose groups (4.10, 8.19, 16.38 g·kg-1)of Buzhong Yiqitang, and selenium yeast tablet group (0.26 mg·kg-1), with 10 mice in each group. Except for the normal group, all other groups were given 0.05% NaI by gavage for eight weeks to establish a model and then received the drug treatment for eight weeks. The serum levels of thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (TgAb) were detected using enzyme-linked immunosorbent assay (ELISA) method. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in mouse thyroid tissue. The immunohistochemical method was used to detect the protein expression of NLRP3, Caspase-1, interleukin-1β (IL-1β), and interleukin-18 (IL-18). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of NLRP3, Caspase-1, IL-1β, and IL-18. Western blot was used to detect the levels of pyroptosis-related proteins in thyroid tissue. ResultCompared with the normal group, the serum levels of TPO-Ab and TgAb in the model group were significantly increased (P<0.01). Thyroid follicles either increased in a cubic shape or were damaged and atrophied, with a large number of lymphocytes infiltrating around the follicles. Compared with the model group, the levels of TPO-Ab and TgAb in other groups were significantly reduced (P<0.01), and the morphology and structure of follicles were improved. The degree of lymphocyte infiltration was reduced. Among them, the medium dose group of Buzhong Yiqitang had the most significant reduction and improvement effect. Compared with the normal group, the positive products and mRNA expression of NLRP3, Caspase-1, IL-1β, and IL-18 proteins in the thyroid tissue of the model group significantly increased (P<0.01), and the protein expression levels of NLRP3, cleaved Caspase-1, IL-1β, IL-18, and GSDMD-N were significantly increased (P<0.05, P<0.01). Compared with the model group, the positive products and mRNA expression of NLRP3, Caspase-1, IL-1β, and IL-18 proteins in other groups were significantly reduced (P<0.05, P<0.01), with the most significant reduction effect in the medium dose group of Buzhong Yiqitang. The protein expression levels of NLRP3, cleaved Caspase-1, IL-1β, IL-18, and GSDMD-N were significantly reduced (P<0.05, P<0.01). ConclusionBuzhong Yiqitang can improve AIT, and its mechanism may be achieved by regulating the NLRP3/Caspase-1/GSDMD signaling pathway to inhibit pyroptosis.
5.Effect of Buzhong Yiqitang on Th17/Treg Immune Imbalance and Notch1 Signaling Pathway in AIT Mice
Zhuo ZHAO ; Nan SONG ; Ziyu LIU ; Pin LI ; Yue LUO ; Pengkun ZHANG ; Zhimin WANG ; Yuanping YIN ; Tianshu GAO ; Zhe JIN ; Xiao YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):19-27
ObjectiveTo explore the effect of Buzhong Yiqitang on the immune imbalance of helper T cell 17 (Th17)/regulatory T cell (Treg) and Notch1 signaling pathway in mice with autoimmune thyroiditis (AIT). MethodA total of 60 8-week-old NOD.H-2h4 mice were randomly divided into the normal group, model group, western medicine group (selenium yeast tablet, 32.5 mg·kg-1), and low-dose (4.78 g·kg-1·d-1), middle-dose (9.56 g·kg-1·d-1), and high-dose (19 g·kg-1·d-1) Buzhong Yiqitang groups, with 10 mice in each group. The normal group was fed with distilled water, and the other groups were fed with water containing 0.05% sodium iodide for eight weeks. After the animal model of AIT was formed spontaneously, the mice were killed under anesthesia after intragastric administration for eight weeks. Serum anti-thyroglobulin antibodies (TGAb), thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroid hormone (FT4) were detected by enzyme-linked immunosorbent assay (ELISA), and thyroid tissue changes were observed by hematoxylin-eosin (HE) staining. The mRNA and protein expressions of retinoid-related orphan receptor-γt (RORγt), interleukin (IL)-17, forkhead box P3 (FoxP3), IL-10, Notch1, and hair division-related enhancer 1 (Hes1) in thyroid tissue were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot, respectively. ResultCompared with the normal group, the thyroid structure of the model group was severely damaged, and lymphocytes were infiltrated obviously. The levels of serum TGAb, FT3, and FT4 contents were significantly increased, and TSH content was significantly decreased (P<0.01). The mRNA and protein expression levels of RORγt, IL-17, Notch1, and Hes1 were significantly increased, while those of FoxP3 and IL10 were significantly decreased in the model group (P<0.01). Compared with the model group, thyroid structural damage and lymphocyte infiltration were improved in the treatment groups, and serum TGAb, FT3, and FT4 contents were significantly decreased. TSH content was increased, and mRNA and protein expression levels of RORγt, IL-17, Notch1, and Hes1 were decreased. mRNA and protein expression levels of FoxP3 and IL-10 were increased to different degrees (P<0.05, P<0.01), and the middle-dose Buzhong Yiqitang group had the most significant intervention effect. ConclusionBuzhong Yiqitang can alleviate the thyroid structural damage in AIT mice, and its mechanism may be related to improving the abnormal differentiation of Th17/Treg immune cells and inhibiting the activation of the Notch1 signaling pathway.
6.Minipigs used in hydrogel wound repair research
Rigeng MEI ; Shaohui GENG ; Zhimin LIN ; Jiapeng WU ; Xin LIU ; Xinyi LAN ; Yuruo GAO ; Guangrui HUANG
Chinese Journal of Tissue Engineering Research 2024;28(29):4697-4702
BACKGROUND:Minipigs are often used in research fields such as skin injury,vascular trauma and cosmetic medicine because they are highly similar to human beings in terms of skin tissue structure and cardiovascular system.Hydrogel as a wound repair drug possesses a variety of excellent physicochemical properties such as strong water retention and adhesion,which can provide isolation moisturization and drug release for wounds. OBJECTIVE:To summarize and conclude the progress of the application of trauma models for different experimental purposes of hydrogel therapy for minipigs,to reveal the development status of various types of minipig trauma models,to analyze the deficiencies of minipig trauma models at the present stage. METHODS:The relevant articles published in Web of Science database and CNKI database from the establishment of each database to 2023 were checked,using"piglet,miniature pig,minipig,miniature pig;gel,hydrogel;trauma,injury,wound,lesion,incision"as Chinese search terms and"Miniature Swine,Miniature pig,minipig;gel,hydrogel;injury,wound,lesion,incision"as English search terms.A total of 438 Chinese and English documents were retrieved,and 59 documents were included in the study through the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)At present,the main models used clinically for trauma repair are large animal species(dogs and pigs),rabbits,and rodents(rats and mice).Because the skin structure of the minipig is more like that of humans,the minipig is the most ideal animal model for trauma repair.(2)In the in-vitro skin injury model,skin defect model is the basic wound model,which can be divided into full skin defect model and medium-thickness skin defect model according to the depth of the wound defect.Burn wound model and infected wound model are multidimensional models with hot metal scald and bacterial culture imposed on the basis of the skin defect model,which have the advantages of high safety coefficient and low operation difficulty.(3)In the in-vivo trauma repair model,mini-pigs are used as esophageal cricothyrotomy model which is more in line with the pathological state of clinical diseases.Mini-pigs are used in the gastric perforation and vascular hemostasis model,which can visually demonstrate the stronger organ adhesion,hemostatic properties and tissue regeneration-promoting effects of the hydrogel.(4)The specific parts of the pig also has the corresponding mode of use:pig ear is usually used to evaluate the hydrogel drug delayed-release effect.Porcine cellular proteins and pig skin collagen are mostly used to prepare composite hydrogels of tissue origin.
7.Association between body composition and coronary artery calcification in patients with chronic kidney disease
Jiajin HAN ; Jingwei GAO ; Zhenjian XU ; Zhimin YUAN ; Ying TANG ; Haifeng ZHANG ; Yangxin CHEN ; Jingfeng WANG ; Pinming LIU
Chinese Journal of Cardiology 2024;52(6):676-683
Objective:To investigate the association between body composition and coronary artery calcification in patients with chronic kidney disease (CKD).Methods:This cross-sectional study enrolled patients with CKD hospitalized from May 2019 to April 2022 at Sun Yat-sen Memorial Hospital, Guangzhou, China. Skeletal muscle mass index and visceral fat area were measured by bioelectrical impedance analysis. Coronary artery calcification was assessed by computed tomography. Patients were divided into coronary artery calcification group and non-coronary artery calcification group according to the incidence of coronary artery calcification. Patients were categorized into tertile groups according to their skeletal muscle mass index and visceral fat area levels ranging from the lowest to the highest levels (T1 to T3). We defined skeletal muscle mass index≤30.4% as low muscle mass and visceral fat area≥80.6 cm 2 as high visceral fat based on the results of the restricted cubic spline graph. All individuals were divided into 4 phenotypes: normal body composition, low muscle mass, high visceral fat, and low muscle mass with high visceral fat. Spearman correlation analysis and logistic regression analysis were used to assess the association between skeletal muscle mass index, visceral fat area and coronary artery calcification. Results:A total of 107 patients with CKD were enrolled, with an age of (60.0±14.1) years, including 41 female patients (38.3%). Patients of coronary artery calcification group had lower skeletal muscle mass index ((32.0±4.8) vs. (34.3±4.8), P=0.016) and higher visceral fat area ((70.8±32.6) cm 2 vs. (47.9±23.8) cm 2, P<0.001) than those of non-coronary artery calcification group. Patients in the T3 group of skeletal muscle mass index had a lower prevalence of coronary artery calcification (17 (48.6%) vs. 28 (77.8%)) and a lower coronary artery calcification score (0.5 (0, 124.0) vs. 12.0 (0.3, 131.0)) than those in the T1 group ( P<0.05). Similarly, patients in the T1 group of visceral fat area had a lower prevalence of coronary artery calcification (14 (40.0%) vs. 29 (80.6%)) and a lower coronary artery calcification score (0 (0, 3.0) vs. 37.0 (2.0, 131.0)) than those in the T3 group ( P<0.05). Likewise, patients with both low muscle mass and low muscle mass with high visceral fat had a higher prevalence of coronary artery calcification (11(78.6%) vs. 33 (47.8%); 15 (83.3%) vs. 33 (47.8%)) and a higher coronary artery calcification score (31.1 (0.8, 175.8) vs. 0 (0, 16.4); 27.6 (6.4, 211.4) vs. 0 (0, 16.4)) than those with normal body composition ( P<0.05). Spearman correlation analysis showed that skeletal muscle mass index was inversely correlated with coronary artery calcification score ( r=-0.212, P=0.028), and visceral fat area was positively correlated with coronary artery calcification score ( r=0.408, P<0.001). Multivariate logistic regression analysis showed that increased skeletal muscle mass index was inversely associated with coronary artery calcification prevalence (T2: OR=0.208, 95% CI: 0.056-0.770, P=0.019; T3: OR=0.195, 95% CI: 0.043-0.887, P=0.034), and reduced visceral fat area was inversely associated with coronary artery calcification prevalence (T1: OR=0.256, 95% CI: 0.071-0.923, P=0.037; T2: OR=0.263, 95% CI: 0.078-0.888, P=0.031). Consistently, both low muscle mass and low muscle mass with high visceral fat were associated with coronary artery calcification prevalence ( OR=6.616, 95% CI: 1.383-31.656, P=0.018; OR=5.548, 95% CI: 1.062-28.973, P=0.042). Conclusion:Reduced skeletal muscle mass index and increased visceral fat area are significantly associated with both the prevalence and severity of coronary artery calcification in patients with CKD.
8.Mechanism of Buzhong Yiqitang in Ameliorating Thyroiditis Damage in AIT Mice by Modulating TLR4/NF-κB/AIM2 Signaling Pathway
Zhuo ZHAO ; Zhe JIN ; Zhengzheng LI ; Xuanlin GUO ; Jiayun LI ; Tongran GAO ; Pin LI ; Zhimin WANG ; Yuanping YIN ; Ziyu LIU ; Xiao YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(18):1-9
ObjectiveTo explore the mechanism of Buzhong Yiqitang in ameliorating inflammatory injury in autoimmune thyroiditis (AIT) mice based on the Toll-like receptor 4(TLR4)/nuclear transcription factor-kappa B(NF-κB)/absent in melanoma 2(AIM2)inflammasome signaling pathway. MethodThe 120 genetically susceptible 8-week-old NOD.H-2h4 mice were selected and randomly divided into control group, model group, low, medium and high dose groups of Buzhong Yiqitang (4.78, 9.56, 19.12 g·kg-1), and western medicine group (selenium yeast tablets, 3.033×10-5 g·kg-1). The AIT model mice in each group drank ad libitum 0.05% sodium iodide aqueous solution for 8 weeks to establish the AIT model, and the control group drank ad libitum distilled water. Eight weeks later, the mice in each dosing group were divided into groups and gavage. The swelling of thyroid tissue was observed with the naked eye, and the weight of spleen was weighed. The content of serum inflammatory factors interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) was measured by enzyme-linked immunosorbent assay (ELISA), and Real-time PCR was used to detect the expression of HMGB1, TLR4, AIM2, NF-κB p65,apoptosis-associated speck-like protein(ASC),cysteinyl aspartate-specific protease-1(Caspase-1), IL-1β mRNA. Western blot was used to detect the expression of high motility group protein 1 (HMGB1), TLR4, AIM2, NF-κB p65, phosphorylation(p)-NF-κB p65, ASC, Caspase-1, and IL-1β proteins in thyroid tissue, and immunofluorescence staining was used to observe the protein expression of HMGB1, AIM2, and NF-κB p65 in thyroid tissue of mice. ResultCompared with the control group, the thyroid tissue of mice in the model group was significantly swollen, the spleen quality was significantly increased, and the expression of HMGB1, TLR4, NF-κB p65, AIM2, ASC, Caspase-1, IL-1β in thyroid tissue was significantly increased (P<0.01). Compared with the model group, the swelling of thyroid tissue in mice in each dose group of Buzhong Yiqitang was improved, the quality of spleen was significantly reduced, and the expression of HMGB1, TLR4, AIM2, NF-κB p65, p-NF-κB p65, ASC, Caspase-1, IL-1β in thyroid tissue was significantly reduced (P<0.05, P<0.01). ConclusionBuzhong Yiqitang can effectively improve the inflammatory injury of AIT, and regulating the abnormal activation of the TLR4/NF-κB/AIM2 inflammasome signal pathway may be one of its intervention mechanisms.
9.Improvement of Thyroid Injury in AIT Mice by Inhibiting Ferroptosis Through Regulation of Nrf2/PPARγ/GPX4 Pathway by Buzhong Yiqitang
Ziyu LIU ; Zhuo ZHAO ; Yiran CHEN ; Huimin CAO ; Si CHEN ; Zhimin WANG ; Tianshu GAO ; Xiao YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(18):10-18
ObjectiveTo investigate the mechanism of Buzhong Yiqitang in ameliorating ferroptosis in autoimmune thyroiditis (AIT) mice based on the nuclear factor erythroid 2-related factor 2 (Nrf2)/peroxisome proliferator-activated receptor γ (PPARγ)/glutathione peroxidase 4 (GPX4) pathway. Method120 SPF-grade 7-8-week-old NOD.H-2h4 mice were randomly divided into control group, model group, low-, medium-, and high-dose Buzhong Yiqitang groups, and western medicine group, with 20 mice in each group. Except for the control group, all mice were fed with classic high-iodine water (0.05% NaI) to induce AIT models after 8 weeks. The low-, medium-, and high-dose Buzhong Yiqitang groups were administered 4.78, 9.56, 19.12 g·kg-1 of Buzhong Yiqitang, respectively, via gavage. The western medicine group was given 3.033×10-5 g·kg-1 selenium yeast tablet suspension via gavage, while the control and model groups were given an equal volume of distilled water via gavage. After 8 weeks of continuous treatment, samples were collected. The pathological morphology of mouse thyroid tissue was observed through hematoxylin-eosin (HE) staining,the content of serumantithyroid peroxidase autoantibody(TPOAb)and anti-thyroglobulin antibodies(TGAb)was measured by enzyme-linked immunosorbent assay (ELISA),the kit was used to detect the levels of superoxide dismutase (SOD), and malondialdehyde (MDA) in mouse serum. Immunofluorescence was used to detect the localized expression of GPX4 in thyroid tissue. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the expression of Nrf2, PPARγ, solute carrier family 7 member 11 (SLC7A11), solute carrier family 3 member 2 (SLC3A2), lysolipid lecithin acyltransferase 3 (LPCAT3), and GPX4 mRNA in thyroid tissue. Western blot was used to detect the expression of Nrf2, PPARγ, SLC7A11, SLC3A2, LPCAT3, and GPX4 proteins in thyroid tissue. ResultCompared with control group, model group under light microscopy showed significant lymphocyte infiltration in the thyroid tissue, significantly increased levels of TGAb and TPOAb in serum (P<0.01), significantly increased MDA levels and decreased SOD levels in serum (P<0.01), significantly decreased expression of Nrf2, PPARγ, SLC7A11, SLC3A2, and GPX4 (P<0.01) in thyroid tissue, while the expression of LPCAT3 was significantly increased (P<0.01). Compared with model group, the Buzhong Yiqitang groups and the western medication group under light microscopy showed lymphocyte infiltration in the thyroid tissue of was decreased, significantly decreased levels of TPOAb and TGAb in serum (P<0.05,P<0.01), decreased MDA levels and increased SOD levels in serum(P<0.05,P<0.01),significantly increased expression of Nrf2, PPARγ, SLC7A11, SLC3A2, and GPX4, while the expression of LPCAT3 was significantly decreased (P<0.05,P<0.01) in the thyroid tissue. Compared with western medication group, Buzhong Yiqitang groups showed significant overall trends in the expression of Nrf2, PPARγ, SLC7A11, SLC3A2, GPX4, and LPCAT3 (P<0.05,P<0.01). ConclusionBuzhong Yiqitang can effectively improve the inflammatory injury of AIT, and its mechanism of action may be related to the regulation of Nrf2/PPARγ/GPX4 to inhibit ferroptosis.
10.Mechanism of Buzhong Yiqitang in Improving Autoimmune Thyroiditis by Regulating Th17 Cells Through miR-155/Ndfip1/Pten Axis
Xiaohui LI ; Zhuo ZHAO ; Yiran CHEN ; Huimin CAO ; Si CHEN ; Zhimin WANG ; Tianshu GAO ; Ziyu LIU ; Xiao YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(18):19-26
ObjectiveTo explore the mechanism of Buzhong Yiqitang in improving autoimmune thyroiditis (AIT) by regulating helper T cell 17(Th17) cells through microRNA-155 (miR-155)/Nedd4 family interaction protein 1 (Ndfip1)/phosphatase and tensin homology (Pten) axis. MethodThe 100 SPF grade 8 week-old NOD.H-2h4 mice were fed with high iodine water (0.05% NaI) for 8 weeks, and AIT model was made. They were divided into model group, Buzhong Yiqitang low-,medium-,and high-dose groups (4.78,9.56,19.12 g·kg-1·d-1) and selenium yeast tablet group (3.033×10-5 g·kg-1) according to random number table method. There were 20 mice in each group and 20 mice in the control group. The control group and the model group were given the same amount of distilled water. After 8 weeks of continuous administration, Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the expression of miR-155-5p, Ndfip1, Pten, protein tyrosine kinase 1 (Jak1), signaling and transcriptional activator 3 (Stat3) retinoic acid-associated orphan receptor γt (RORγt), and interleukin-17 (IL-17) mRNA in mouse thyroid tissue. Western blot was used to detect the expression of Ndfip1, Pten, Jak1, Stat3, RORγt, and IL-17 proteins in mouse thyroid tissue, immunohistochemical method was used to detect the expression of Ndfip1 and Pten proteins in mouse thyroid tissue; flow cytometry was used to detect the proportion of Th17 cells in mouse spleen. ResultCompared with the control group, the proportion of Th17 cells was increased (P<0.01). The expressions of miR-155-5p, Jak1, Stat3, RORγt and IL-17 were increased (P<0.01), while the expressions of Ndfip1 and Pten were decreased (P<0.01). Compared with model group, the proportion of Th17 cells was decreased (P<0.05,P<0.01). The expressions of miR-155-5p, Jak1, Stat3, RORγt and IL-17 were decreased (P<0.05,P<0.01), while the expressions of Ndfip1 and Pten were increased (P<0.05,P<0.01). ConclusionThe application of Buzhong Yiqitang can improve the autoimmune disorder of AIT mice, the mechanism of which may be related to the regulation of Ndfip1/Pten axis by miR-155 and then the regulation of Th17 cell differentiation.


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