1.Correlation of "Parts-components-properties" of Traditional Chinese Medicines from Latex-containing Plants
Jianglong HE ; Baoyu JI ; Panpan LI ; Xiuqing LI ; Wange WU ; Suiqing CHEN ; Chengming DONG ; Lixin PEI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):124-132
ObjectiveTo investigate the correlation among the botanical characteristics, biological characteristics, chemical composition, and medicinal properties and efficacy of traditional Chinese medicines (TCM) from latex-containing plants, so as to strengthen the theory of "identifying symptoms for qualities" and provide a reference for the development and utilization of the latex-containing plant resources. MethodStatistics on the meridians for properties and tastes, efficacy, medicinal parts, family and genus, and chemical components of TCM from latex-containing plants were carried out. A total of 53 TCM from latex-containing plants included in the 2020 edition of the Chinese Pharmacopoeia were screened by mining the Chinese Botanical Journal, Chinese Materia Medica, Dictionary of Traditional Chinese Medicines, and related literature. In addition, their meridians for properties and tastes, medicinal parts, chemical components, and TCM classifications were summarized and statistically analyzed by using Excel 2013 and ChiPlot 2023.3.31 software. ResultIt was found that latex-containing plants were mainly distributed in one kingdom, one phylum, two classes, and 20 families, and most of the TCM from latex-containing plants belonged to Dicotyledonaceae under Angiosperms. In terms of properties and tastes, plain>cold>warm>cool>hot and bitter>pungent>sweet>sour>salty. In terms of meridians, liver>lung>kidney>spleen=large intestine=stomach>heart>bladder=gallbladder=small intestines. In terms of medicinal parts, roots (root, rhizomes, tuberous root, and root bark)>resin>seed>whole herb (whole herb and above-ground part)>stem (stem and branch)>fruit>leaf>flower=skin. In terms of research on chemical components, they were mostly glycosides. In terms of TCM classification, they were mostly medicines for activating blood circulation and removing blood stasis. ConclusionThe TCM from latex-containing plants is mainly plain, with a uniform warm and cold distribution. The tastes are mainly bitter and pungent, and the major meridians are the liver and lung. The roots and resins are mainly used as medicines. The components mostly contain glycosides, alkaloids, and volatile oils, and most of them are medicines for activating blood circulation and removing blood stasis, as well as for removing heat and toxins. There is a certain degree of correlation among the growth habits, medicinal parts, chemical components, and the properties, tastes, and efficacy of the TCM from latex-containing plants. It may provide a reference for resource development and utilization of TCM from latex-containing plants.
2.Correlation Analysis of Traditional Chinese Medicines from Fungi Based on "Habit-Growth Environment-part-medicinal Properties"
Xiuqing LI ; Baoyu JI ; Jianglong HE ; Panpan LI ; Wange WU ; Suiqing CHEN ; Chengming DONG ; Lixin PEI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):133-139
ObjectiveThe relevant laws among the biological characteristics, medicinal parts, growth environment, and medicinal properties and efficacy of traditional Chinese medicines (TCM) from fungi were excavated, so as to strengthen the theory of distinguishing symptoms for quality and provide a reference for the development and utilization of TCM from fungi. MethodThe medicinal parts, meridians for properties and tastes, heterotrophic mode, and efficacy of commonly used TCM from fungi were summarized. By consulting the Compendium of Materia Medica, Shennong Materia Medica, Flora of China, and literature, the TCM from fungi indexed in the 2020 edition of the Chinese Pharmacopoeia and some local pharmacopeias were checked. ResultA total of 28 common TCM from fungi were selected. Different TCMs from fungi have different meridians for properties and tastes, medicinal parts, habits, and growth environments. The relevant information was counted. Among the four properties, plain>cold>warm. Among the five tastes, sweet>bitter>light>pungent=salty. In terms of medicinal parts, fruiting body>sclerotia>complex>spermia=outer skin=other. In terms of meridians, lung>liver=heart>spleen=kidney>stomach. In terms of habits, parasitism>saprophysis>symbiosis=facultative parasitism=facultative saprophysis. ConclusionTCM from fungi are mainly parasitic and saprophytic, and the plain property and sweet taste the most. The meridians are mostly lung, heart, and liver. Nourishment and diuresis are the main efficacy. There is a certain correlation between the color, habit, medicinal parts, and growth environment of TCM from fungi and their properties, tastes, and efficacy, providing comprehensive literature reference and theoretical basis for their in-depth research, clinical use, and resource development.
3.Correlation of "Medicinal Tissue-property, Taste, and Efficacy-clinical Application" of Traditional Chinese Medicine from Plant Skin
Panpan LI ; Baoyu JI ; Jianglong HE ; Xiuqing LI ; Wange WU ; Suiqing CHEN ; Chengming DONG ; Lixin PEI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):149-158
ObjectiveTo investigate the functions and characteristics of traditional Chinese medicine (TCM) from plant skin and their Chinese patent medicines and explore the related laws of the medicinal tissue, property, taste, efficacy, and clinical application, so as to strengthen the theory of identifying symptoms for qualities and provide references for the development and utilization of TCM from plant skin and their Chinese patent medicines. MethodBy reviewing the 2020 edition of the Chinese Pharmacopoeia and some local pharmacopeias, TCM from plant skin and their Chinese patent medicines were screened out, and the characteristics, functions, and precautions of TCM from plant skin and their Chinese patent medicines were summarized. Statistical analysis was carried out with Excel. ResultA total of 62 TCM from plant skin were found, mainly distributed in one kingdom, three phyla, and 31 families. In terms of the family genus, Rutaceae>Leguminosae>Cucurbitaceae. In terms of the medicinal tissue, bark>root bark>fruit bark>seed bark. In terms of property and taste, warm>cold>plain>cool>hot, and bitter>sweet=pungent>acidic. In terms of meridians, lung>liver>spleen>heart>colorectal>kidney>stomach=bladder. In terms of TCM classification, most of them belong to the category of heat-clearing medicines. There were 485 types of Chinese patent medicines from plant skin, with the most Chinese patent medicines containing Citri Reticulatae Pericarpium. Among the forms of administration, pills were the most predominant. In terms of the tastes of the medicines, bitter and sweet flavors predominated. In terms of functions, medicines for strengthening the body resistance were the most. For the precautions, contraindications during pregnancy were the most common. ConclusionThere is a correlation among medicinal tissue, property, taste, efficacy, and clinical application of TCM from plant skin. It is also necessary to pay attention to the contraindications of the medicines and rationally choose TCM from plant skin and their Chinese patent medicines under the guidance of TCM theory based on syndrome differentiation and treatment.
4.Expert opinions on operation rules of Morita therapy outpatient service
Jiangbo LI ; Zucheng WANG ; Yuhua CUI ; Yingzhi LU ; Weijie QU ; Haiyin ZHANG ; Fuqiang MAO ; Fengqing QIE ; Wanghong SHI ; Qinfeng ZHANG ; Lingyi PAN ; Ling ZHANG ; Jianzhong LI ; Guangcheng CUI ; Tongxian CHEN ; Xiuqing MA ; Wei RONG ; Jianjun ZHANG ; Qingfang ZHONG ; Yanchi ZHANG ; Boquan ZHANG ; Xinrui WANG ; Wenyou MA ; Qingtao REN ; Yongfa JING ; Huanzhong LIU ; Zhenjian YU ; Laitian ZHAO ; Tianming HAN ; Xue HAN
Chinese Mental Health Journal 2024;38(1):68-72
Morita therapy has been bom for more than 100 years.Inpatient Morita therapy is highly oper-able and easy to master.It can improve many refractory neuroses through four-stage treatment.But more neuroses are treated in outpatient clinics,and Morita therapy cannot be used in hospitalized patients.Therefore,the formula-tion of expert opinions on outpatient operations is particularly important.This paper is based on domestic and for-eign references,and after many discussions by domestic Morita therapy experts,and then drew up the first version of the expert opinions on operation of outpatient Morita therapy.Meanwhile the operation rule of Morita therapy in three stages of outpatient treatment was formulated:in the etiological analysis stage,under the theoretical guidance of Morita therapy,analyze the pathogenic factors,to improve treatment compliance and reduce resistance;during the operating stage,guide patients to engage in constructive and meaningful actions,realizing the achievement of letting nature take its course principle;in the cultivating character and enriching life stage,pay attention to positive infor-mation,expanding the scope and content of actions,improving the ability to adapt to complex life,and preventing recurrence caused by insufficient abilities.It will lay a foundation for the promotion of Morita therapy in domestic outpatient clinics,so that more patients with neurosis and other psychological diseases could receive characteristic Morita therapy treatment in outpatient clinics.
5.Effects of Zamerovimab/Mazorelvimab on the rabies virus neutralizing antibody level in the grade Ⅲ rabies post exposure subjects
Xiuqing WANG ; Yongxian ZHA ; Zhengxiong WANG ; Ya JIANG ; Xiangyu ZHANG ; Jiangshu GUO ; Jingyu LI ; Xiaoqiang LIU
Chinese Journal of Experimental and Clinical Virology 2024;38(4):388-394
Objective:This study aimed to evaluate the immunoprotective effect of anti-rabies virus cocktail monoclonal antibody Zamerovimab/Mazorelvimab after rabies exposure.Methods:The dynamic data of rabies virus neutralizing antibody (RVNA) were analyzed in the Zamerovimab/Mazorelvimab Chinese phase Ⅲ study (clinical trial registration number: CTR20201819).Results:The full analysis set showed that RVNA geometric mean titers (GMT) on the 4 th, 8 th, 15 th, 43 rd, and 99 th day in the Zamerovimab/Mazorelvimab group were 4.413 IU/ml, 5.178 IU/ml, 17.062 IU/ml, 14.672 IU/ml, and 2.836 IU/ml, respectively, while those in the human rabies immunoglobulin (HRIG) group were 0.299 IU/ml, 0.451 IU/ml, 11.374 IU/ml, 18.063 IU/ml, and 6.769 IU/ml, respectively. The positive rates of RVNA on the 4 th, 8 th, 15 th, 43 rd, and 99 th day in the Zamerovimab/Mazorelvimab group were 99.9%, 99.6%, 100%, 100%, and 97.4%, respectively, while those in the HRIG group were 23.3%, 34.1%, 97.6%, 99.6%, and 98.4%, respectively. Conclusions:Compared with HRIG, Zamerovimab/Mazorelvimab cocktail monoclonal antibody reached the required protection level of RVNA very soon, thus effectively provided an immediate neutralizing effect of passive immunization therapies against rabies virus.
6.The role of tofacitinib in early atherosclerosis in mice with systemic lupus erythematosus
Qu CHEN ; Fengmei GE ; Zhao LI ; Qiushuang ZHANG ; Xue WU ; Qi CHEN ; Saiqi LI ; Xuebin WANG ; Xiuqing YAN
Chinese Journal of Rheumatology 2024;28(2):106-112
Objective:To investigate the effect of tofacitinib on early atherosclerosis of patients with systemic lupus erythematosus and explore the possible relationship between lupus nephritis and early atherosclerosis of systemic lupus erythematosus.Methods:Sixteen 8-week-old female MRL/lpr mice with a body weight of 20~25 g were selected and randomly divided into the treatment group and placebo group, with 8 mice in each group. The treatment group diluted tofacitinib by normal saline, and given at a dose of 10 mg·kg -1·d -1, and the placebo group (starch tablets) administered the medication in the same way as the treatment group for a total of 8 weeks. The ELISA method was applied to detect serum anti-dsDNA antibody levels in the two groups of mice. Bradford method protein concentration was used to determine the level of urine protein in mice. Automatic biochemical analyzer was used to detect blood lipids, urea nitrogen, serum creatinine, complement C3, complement C4 levels. Western blotting was used to determine the protein expression levels of monocyte chemoattractant protein-1 (MCP-1), non-receptor protein tyrosine kinase family 1 (JAK1), signal transducer and activator of transcription 1 (STAT1) and signal transducer and activator of transcription 2 (STAT2) in aortic and kidney tissues. After the aortic arch section were prepared, oil red O was used to stain the sections, and the vascular plaque area and intimal thickness were evaluated by ImageJ software. The kidneys were dissected and stained with HE, and the active lesions of lupus nephritis were evaluated using the glomerular activity scoring system. SPSS 23.0 software was used for statistical analysis, in which the between-group comparison was performed using two independent samples t-test, and the correlation analysis was performed using the Spearman method. Results:①The serum anti-dsDNA antibody expression level in the treatment group [(5.2±1.0) U/ml] was lower than that in the placebo group [(6.9±1.2) U/ml], ( Z=-3.07, P=0.008), and the levels of complement C3 and complement C4 were higher than those in the placebo group [(293±10) mg/L vs. (260±19) mg/L, Z=2.72, P=0.017]; (16±6) mg/L vs. (8±9) mg/L, Z=3.78, P=0.006]. There was no significant difference in serum BUN and Scr between the treatment group and the placebo group [(10.6±0.7) mmol/L vs. (11.5±1.1) mmol/L, Z=-1.96, P=0.071; (17±5) μmol/L vs. (22±6) μmol/L, Z=-1.79, P=0.095]. ② Compared with the placebo group, the levels of LDL, TC and TG in the treatment group decreased [(0.83±0.15) mmol/L vs. (1.08±1.05) mmol/L, Z=-3.95, P=0.001; (2.90±0.08) mmol/L vs. (1.81±0.97) mmol/L, Z=-5.17, P=0.001; (1.10±0.08) mmol/L vs. (1.60±0.42) mmol/L, Z=-3.23, P=0.013], and HDL level increased [(2.02±0.99) mmol/L vs. (1.81±0.97) mmol/L, Z=4.42, P=0.001]. ③ Compared with the placebo group, the levels of aortic MCP-1, JAK1, STAT1 and STAT2 in the treatment group were reduced [(0.17±0.30) vs. (0.23±0.05), Z=-3.06, P=0.009; (0.83±0.09) vs. (1.05±0.19), Z=-3.07, P=0.008; (0.77±0.07) vs. (0.94±0.13), Z=-2.83, P=0.014; (0.70±0.07) vs. (0.82±0.09), Z=-2.83, P=0.013], the aortic plaque area and aortic intimal thickness were lower than those in the placebo group [(12±31) μm 2vs. (1 242±1 101) μm 2, Z=-3.12, P=0.016; (63±7) μm vs. (82.10±8.06) μm, Z=-5.13, P<0.001]. ④ Compared with the placebo group, the urine protein level and glomerulonephritis activity score in the treatment group were decreased [(0.08±0.03) mg/mL vs. (0.20±0.11) mg/mL, Z=-3.08, P=0.015; (1.79±0.38) vs. (2.79±0.14) points, Z=-7.08, P<0.001)], and renal tissue MCP-1, JAK1, STAT1.Compared with the placebo group, STAT2 levels were reduced [(0.364±0.040) vs. (0.425±0.021), Z=-3.85, P=0.003; (0.689±0.074) vs. (0.838±0.068), Z=-4.19, P=0.001; (0.508±0.070) vs. (0.646±0.019), Z=-2.85, P=0.015; (0.618±0.062) vs. (0.740±0.101), Z=-2.94, P=0.013. ⑤ The glomerular mobility scores of the two groups were positively correlated with LDL, TCHO, TG, aortic plaque area and aortic intimal thickness ( r=0.51, P=0.043; r=0.79, P<0.001; r=0.64, P=0.008; r=0.82, P<0.001; r=0.74, P=0.001), and negatively correlated with HDL ( r=-0.53, P=0.036). The urine protein levels in the two groups were positively correlated with LDL, TC, TG, aortic plaque area and aortic intimal thickness ( r=0.67, P=0.004; r=0.68, P=0.004; r=0.53, P=0.033; r=0.80, P<0.001; r=0.74, P=0.001), and negatively correlated with HDL ( r=-0.57, P=0.021). Conclusion:The severity of lupus nephritis is correlated with atherosclerosis and dyslipidemia in the early stage of systemic lupus erythematosus. Tofacitinib may reduce the degree of early arteriosclerosis and lupus nephritis in MRL/LPR mice, and reduce blood lipid levels, which may be effective in improving the prognosis of SLE and improving the survival rate of patients.
7."Medicinal Part-Habitat-Nature, Taste, and Effect" Correlations of Pteridophyte-derived Chinese Medicinal Materials
Wange WU ; Baoyu JI ; Jianglong HE ; Xiuqing LI ; Panpan LI ; Suiqing CHEN ; Chengming DONG ; Hongxin CUI ; Lixin PEI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(22):204-211
ObjectiveTo explore the correlations between botanical characteristics, biological characteristics, growth environment, and medicinal properties of common pteridophyte-derived Chinese medicinal materials, thus providing evidence for the theory of quality evaluation through morphological identification and giving insights into the extensive and reasonable application of pteridophytes in traditional Chinese medicine (TCM). MethodThe medicine parts, habitats, natures, tastes, and effects of the commonly used pteridophyte-derived Chinese medicinal materials were summarized. The commonly used pteridophyte-derived Chinese medicinal materials were retrieved from the Pharmacopoeia of China, Dictionary of Chinese Materia Medica, and related literature. Excel 2016, ChiPlot, Cytoscape 3.7.1, SPSS 21.0, and weiciyun software were used for statistical analysis. ResultThe frequency of the habitats followed the trend of streamside wetland>tree trunk and rock crevices>sunslope>water surface. The frequency of medicinal parts presented the trend of whole plant>rhizome>leaf>dried aboveground part>spore. The frequency of natures was in the order of cool>cold>plain>warm>hot, and that of tastes was in an order of bitter>pungent>sweet>bland>salty. The frequency of meridian tropism followed the trend of liver meridian>stomach meridian>lung meridian>kidney meridian>bladder meridian>heart meridian>large intestine meridian>spleen meridian>small intestine meridian. The effects of the pteridophyte-derived Chinese medicinal materials followed a frequency trend of clearing heat and detoxifying>promoting urination and relieving stranguria>cooling blood and stopping bleeding>activating blood and resolving stasis>dispelling wind and eliminating dampness. ConclusionThe pteridophyte-derived Chinese medicinal materials mainly have a cool nature, a bitter taste, and tropism to the liver meridian. Whole plants and roots are mainly used for medicinal purposes, and most of these plants grow in the wetlands near rivers, under trees, and in tree trunk and rock crevices. The main effects of these medicinal materials are clearing heat and detoxifying, dispelling wind and removing dampness, cooling blood and stopping bleeding, activating blood and resolving stasis, and soothing meridians and dredging collaterals. There are certain correlations between the structures, habitats, medicinal parts, and effects of pteridophyte-derived Chinese medicinal materials, which provide reference for the development and utilization of pteridophyte-derived Chinese medicinal material resources.
8.Progress and prospects of dental pulp stem cells in diabetes treatment
Ailan HUANG ; Peipei GUO ; Xiaoqing LU ; Jintao WU ; Zehan LI ; Xiuqing XU ; Juan WANG ; Lili ZHOU
STOMATOLOGY 2024;44(6):452-457
Diabetes mellitus(DM)stands as a chronic metabolic ailment predominantly characterized by elevated blood glucose lev-els,stemming from either a resistance to insulin or aberrations in insulin secretion.The ensuing persistent hyperglycemia,a direct con-sequence of pancreatic β-cell devastation,acts as a catalyst for a myriad of complications,inclusive of extensive neuropathies.The dis-ease has substantial prevalence and mortality rates,underscoring the gravity of its impact on public health.Dental pulp stem cells(DPSCs)are readily obtainable,and they exhibit a profound capacity for self-renewal,multi-lineage differentiation,and vigorous pro-liferation.Remarkably,DPSCs can differentiate into pancreatic β-cells,subsequently participate in insulin secretion and play a pivotal role in immune modulation.This has achieved notable advancements in the therapeutic domain,particularly in the treatment of chronic diseases.Furthermore,DPSCs harbor the potential to mitigate symptoms in patients afflicted with type 1 diabetes.They navigate this therapeutic pathway through mechanisms that involve suppressing autoimmunity,modulating inflammatory responses,and counteracting oxidative stress.This article meticulously reviews the biological characteristics inherent to DPSCs and explores their multifaceted thera-peutic potential in addressing DM and its associated complications.Through this endeavor,the article aims to contribute to the refine-ment and enhancement of DM management strategies.
9.Analysis on Difference Between Ancient Decocting Methods and Modern Decocting Methods of Yihuangtang
Yanqiu WU ; Yuling LIU ; Xiuqing WANG ; Longfei LIN ; Anhui YANG ; Yingying ZHOU ; Hui LI
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(3):152-159
ObjectiveTo explore the differences between the ancient decocting methods and modern decocting method of Yihuangtang by taking the dry extract rate, the content of active ingredients and the fingerprint information as indicators, so as to provide reference for the preparation of benchmark samples and the development of compound preparations of this famous classical formula. MethodAccording to the three decocting methods recorded in Paozhi Dafa and Jianming Yigou and Management Specifications of Traditional Chinese Medicine Decoction Chambers in Medical Institutions, the Yihuangtang was decocted respectively. The polysaccharide content in the samples was determined by ultraviolet spectrophotometer (UV) at 488 nm, and the contents of alkaloids (berberine hydrochloride, phellodendrine chloride and magnoflorine) in the samples and their fingerprint profiles were determined by high performance liquid chromatography (HPLC), and the dry extract rate was combined to compare the differences of the three decocting methods of Yihuangtang. Among them, the fingerprint was gradient eluted with acetonitrile (A) -0.1% phosphoric acid aqueous solution (B) as mobile phase (0-10 min, 5%-8%A; 10-35 min, 8%A; 35-45 min, 8%-12% A; 45-75 min, 12%-17%A; 75-105 min, 17%-35%A; 105-110 min, 35%-100%A; 110-112 min, 100%-5%A; 112-122 min, 5%A), and the detection wavelength was 230 nm. ResultWhen the decoction was carried out according to the method described in Paozhi Dafa, the content of polysaccharides was higher than that of the modern decocting method and the method described in Jianming Yigou. However, the contents of berberine hydrochloride, phellodendrine chloride and magnoflorine were the highest in the modern decocting method. Meanwhile, the number of peaks in fingerprint of the samples prepared by the three decocting methods was basically the same, and 13 common peaks were matched, and the three common peaks of berberine hydrochloride, phellodendrine chloride and magnoflorine were identified. However, the relative peak areas of the common peaks in the fingerprint of the samples prepared by the three decocting methods varied greatly, suggesting that there were differences in the extracting effects of different decocting methods. In addition, there were also differences in the dry extract rate among the three decocting methods of Yihuangtang, and the highest value was obtained by decocting the samples according to the method recorded in Paozhi Dafa. ConclusionDecocting method can affect the dry extract rate, fingerprint information and active ingredient content of Yihuangtang, among which the modern decocting method is conducive to the extraction of alkaloids and the preparation transformation of this famous classical formula, and it is recommended to determine its preparation process by optimizing the modern decocting method.
10.Aureane-type sesquiterpene tetraketides as a novel class of immunomodulators with interleukin-17A inhibitory activity.
Xin TANG ; Chuanxi WANG ; Lei WANG ; Feifei REN ; Runqiao KUANG ; Zhenhua LI ; Xue HAN ; Yiming CHEN ; Guodong CHEN ; Xiuqing WU ; Jie LIU ; Hengwen YANG ; Xingzhong LIU ; Chen WANG ; Hao GAO ; Zhinan YIN
Acta Pharmaceutica Sinica B 2023;13(9):3930-3944
Interleukin (IL)-17A, a pro-inflammatory cytokine, is a fundamental function in the onset and advancement of multiple immune diseases. To uncover the primary compounds with IL-17A inhibitory activity, a large-scale screening of the library of traditional Chinese medicine constituents and microbial secondary metabolites was conducted using splenic cells from IL-17A-GFP reporter mice cultured under Th17-priming conditions. Our results indicated that some aureane-type sesquiterpene tetraketides isolated from a wetland mud-derived fungus, Myrothecium gramineum, showed remarkable IL-17A inhibitory activity. Nine new aureane-type sesquiterpene tetraketides, myrogramins A-I ( 1, 4- 11), and two known ones ( 2 and 3) were isolated and identified from the strain. Compounds 1, 3, 4, 10, and 11 exhibited significant IL-17A inhibitory activity. Among them, compound 3, with a high fermentation yield dose-dependently inhibited the generation of IL-17A and suppressed glycolysis in splenic cells under Th17-priming conditions. Strikingly, compound 3 suppressed immunopathology in both IL-17A-mediated animal models of experimental autoimmune encephalomyelitis and pulmonary hypertension. Our results revealed that aureane-type sesquiterpene tetraketides are a novel class of immunomodulators with IL-17A inhibitory activity, and hold great promise applications in treating IL-17A-mediated immune diseases.

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