1.Exploring on Processing Mechanism of Enhanced "Invigorating Spleen and Stopping Diarrhea" Effect of Soil-fried Atractylodis Macrocephalae Rhizoma Based on "Microscopic Characterization, Chemical Analysis and Pharmacodynamic Evaluation" Trinity
Guoshun SHAN ; Yuyan XIAO ; Chu YUAN ; Xiuai CHEN ; Qimiao ZHAO ; Xiang LIU ; Hao WU ; Ke ZHANG ; Siqi LIU ; Yongduo YU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):182-193
ObjectiveTo analyze the processing mechanism underlying the enhanced effect of invigorating spleen and stopping diarrhea of soil-fried Atractylodis Macrocephalae Rhizoma(AMR) by analyzing the changes of microstructure, chemical composition and anti-ulcerative colitis(UC) activity before and after soil stir-frying. MethodsThe microstructure and elemental composition of AMR before and after soil stir-frying were analyzed by scanning electron microscopy-energy dispersive spectroscopy(SEM-EDS), to investigate the differences in microstructure and the underlying causes. Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) coupled with UNIFI 1.9.2 natural product analysis platform were used to analyze and identify the chemical constituents in raw and soil-fried products, and multivariate statistical methods including principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to explore the differences and sources of chemical constituents between them. A dextran sulfate sodium(DSS)-induced UC mouse model was established. The method of disease activity index(DAI) was used to evaluate the severity of intestinal inflammation. Hematoxylin-eosin(HE) staining was used to observe the pathological changes of colon tissue, enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory factors, Real-time quantitative polymerase chain reaction(Real-time PCR) and Western blot were used to analyze the expressions of key genes and proteins involved in the intestinal mucosal barrier. The 16S rRNA sequencing was used to evaluate the diversity of intestinal flora, headspace gas chromatography-mass spectrometry(HS-GC-MS) was used to explore the levels of short-chain fatty acids(SCFAs) in feces. Base on the above findings, this paper investigated the effects of raw and soil-fried AMR on the biological, chemical, mechanical and immune barriers of model animals, and the differences in pharmacological effects and underlying mechanisms from the perspective of regulating the intestinal mucosal barrier in UC mice. ResultsSEM observation revealed numerous hearth soil particles on the surface of soil-fried AMR, accompanied by bubble-like bulges. At the same time, there were many cracks and folds on the surface of the hearth soil. EDS analysis revealed that the contents of Si, Al, Mg and Ca in soil-fried AMR were significantly higher than those of raw products, and these elements constituted the primary components of hearth soil. UPLC-Q-TOF-MS combined with database comparison was used to identify the chemical constituents of raw and soil-fried AMR. In positive ion mode, a total of 132 components were identified, primarily comprising three categories of terpenoids, polyphenols and amino acids. In negative ion mode, a total of 40 components were identified, primarily polyphenolic and glycoside compounds. Among them, the contents of sesquiterpenes and polyphenolic acids were changed significantly before and after processing. Soil-fried AMR could reduce the DAI score of UC mice, alleviate the shortening of colon length, reduce the levels of pro-inflammatory factors such as interleukin(IL)-17, IL-18, γ-interferon(IFN-γ) and tumor necrosis factor(TNF)-α in serum, increase the levels of anti-inflammatory factors such as secretory immunoglobulin A(sIgA), IL-10, IL-4 and transforming growth factor-β(TGF-β) in serum, increase the expressions of key genes and proteins of intestinal mucosal barrier such as tight junction protein-1(ZO-1), Occludin, Claudin-1 and mucin 2(MUC2) in colonic mucosa, and improve the disorders of intestinal flora diversity and the levels of SCFAs(P<0.05, P<0.01). The raw and stir-fried products of AMR also exhibited the aforementioned effects, but they were weaker than the soil-fried products. Additionally, the auxiliary material hearth soil also had a certain pharmacodynamic effect. ConclusionSoil-fried AMR can enhance the protective effect on intestinal mucosal barrier in UC mice. These changes or heating-induced alterations in the microscopic structure and chemical composition of AMR may be attributed to the dual effects of adsorption of hearth soil.
2.Exploring on Processing Mechanism of Enhanced "Invigorating Spleen and Stopping Diarrhea" Effect of Soil-fried Atractylodis Macrocephalae Rhizoma Based on "Microscopic Characterization, Chemical Analysis and Pharmacodynamic Evaluation" Trinity
Guoshun SHAN ; Yuyan XIAO ; Chu YUAN ; Xiuai CHEN ; Qimiao ZHAO ; Xiang LIU ; Hao WU ; Ke ZHANG ; Siqi LIU ; Yongduo YU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):182-193
ObjectiveTo analyze the processing mechanism underlying the enhanced effect of invigorating spleen and stopping diarrhea of soil-fried Atractylodis Macrocephalae Rhizoma(AMR) by analyzing the changes of microstructure, chemical composition and anti-ulcerative colitis(UC) activity before and after soil stir-frying. MethodsThe microstructure and elemental composition of AMR before and after soil stir-frying were analyzed by scanning electron microscopy-energy dispersive spectroscopy(SEM-EDS), to investigate the differences in microstructure and the underlying causes. Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) coupled with UNIFI 1.9.2 natural product analysis platform were used to analyze and identify the chemical constituents in raw and soil-fried products, and multivariate statistical methods including principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to explore the differences and sources of chemical constituents between them. A dextran sulfate sodium(DSS)-induced UC mouse model was established. The method of disease activity index(DAI) was used to evaluate the severity of intestinal inflammation. Hematoxylin-eosin(HE) staining was used to observe the pathological changes of colon tissue, enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory factors, Real-time quantitative polymerase chain reaction(Real-time PCR) and Western blot were used to analyze the expressions of key genes and proteins involved in the intestinal mucosal barrier. The 16S rRNA sequencing was used to evaluate the diversity of intestinal flora, headspace gas chromatography-mass spectrometry(HS-GC-MS) was used to explore the levels of short-chain fatty acids(SCFAs) in feces. Base on the above findings, this paper investigated the effects of raw and soil-fried AMR on the biological, chemical, mechanical and immune barriers of model animals, and the differences in pharmacological effects and underlying mechanisms from the perspective of regulating the intestinal mucosal barrier in UC mice. ResultsSEM observation revealed numerous hearth soil particles on the surface of soil-fried AMR, accompanied by bubble-like bulges. At the same time, there were many cracks and folds on the surface of the hearth soil. EDS analysis revealed that the contents of Si, Al, Mg and Ca in soil-fried AMR were significantly higher than those of raw products, and these elements constituted the primary components of hearth soil. UPLC-Q-TOF-MS combined with database comparison was used to identify the chemical constituents of raw and soil-fried AMR. In positive ion mode, a total of 132 components were identified, primarily comprising three categories of terpenoids, polyphenols and amino acids. In negative ion mode, a total of 40 components were identified, primarily polyphenolic and glycoside compounds. Among them, the contents of sesquiterpenes and polyphenolic acids were changed significantly before and after processing. Soil-fried AMR could reduce the DAI score of UC mice, alleviate the shortening of colon length, reduce the levels of pro-inflammatory factors such as interleukin(IL)-17, IL-18, γ-interferon(IFN-γ) and tumor necrosis factor(TNF)-α in serum, increase the levels of anti-inflammatory factors such as secretory immunoglobulin A(sIgA), IL-10, IL-4 and transforming growth factor-β(TGF-β) in serum, increase the expressions of key genes and proteins of intestinal mucosal barrier such as tight junction protein-1(ZO-1), Occludin, Claudin-1 and mucin 2(MUC2) in colonic mucosa, and improve the disorders of intestinal flora diversity and the levels of SCFAs(P<0.05, P<0.01). The raw and stir-fried products of AMR also exhibited the aforementioned effects, but they were weaker than the soil-fried products. Additionally, the auxiliary material hearth soil also had a certain pharmacodynamic effect. ConclusionSoil-fried AMR can enhance the protective effect on intestinal mucosal barrier in UC mice. These changes or heating-induced alterations in the microscopic structure and chemical composition of AMR may be attributed to the dual effects of adsorption of hearth soil.
3.Efficacy and safety of anlotinib combined with ICI as first-line treatment for advanced lung squamous cell carcinoma: a single-center retrospective cohort study of 37 patients
LIN Yong1△ ; XIAO Chunmei2△ ; XIE Qiang2 ; CHEN Qun2 ; SHI Qin2 ; LUO Yang2 ; HU Ying2 ; LIN Heng2
Chinese Journal of Cancer Biotherapy 2026;33(2):155-162
[摘 要] 目的:探讨安罗替尼联合免疫检查点抑制剂(ICI)作为一线方案治疗晚期肺鳞状细胞癌(LUSC)的有效性及安全性。方法:采用单中心回顾性队列设计,连续纳入2018年10月至2023年12月福建省福州肺科医院收治的37例初治晚期LUSC患者。所有患者接受安罗替尼(剂量为8、10或12 mg/d,用药2周/停药1周)联合ICI治疗。主要终点为无进展生存期(PFS),次要终点包括客观缓解率(ORR)、疾病控制率(DCR)及治疗相关不良事件(TRAE)。结果:全组患者中位随访15.2个月,ORR达54.1%(20/37),DCR为97.3%(36/37),中位PFS为11.8个月(95%CI:8.3~NA),12个月PFS率为48.6%。探索性亚组分析显示:安罗替尼12 mg剂量组的中位PFS(未达到 vs 7.5个月,HR = 0.09,95%CI:0.01~0.67,P < 0.01)及ORR(100% vs 42.9%,P < 0.01)均显著优于8/10 mg组。分期分层显示ⅢB/ⅢC期患者ORR显著优于Ⅳ期(84.6% vs 41.7%,P = 0.02)。安全性方面,62.2%(23/37)的患者发生TRAE,以1~2级高血压[29.7%(11/37)]、手足综合征[21.6%(8/37)]为主,3例(8.1%)因3级TRAE终止治疗。结论:安罗替尼联合ICI作为晚期LUSC一线治疗方案具有良好的疗效前景和可管理的安全性。其中,12 mg剂量组在探索性分析中显示出更优疗效的潜在信号,早期分期患者ORR更高。该结果值得开展大规模前瞻性研究进行进一步验证。
4.Causal relationship between gut microbiota and idiopathic pulmonary fibrosis: A bi-directional two-sample Mendelian randomization study
Xuanyu WU ; Xiang XIAO ; Jiajing CHEN ; Xiaomin YU ; Han YANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(04):584-591
Objective To investigate the causal relationship between gut microbiota and idiopathic pulmonary fibrosis (IPF). Methods Genome-wide association studies (GWAS) data of gut microbiota and IPF were obtained from MiBioGen and IEU OpenGWAS, respectively. Instrumental variables were screened by means of significance, linkage disequilibrium, weak instrumental variable screening, and removal of confounding factors (genetics, smoking, host characteristics). Inverse variance weighted (IVW) was used as the main Mendelian randomization (MR) analysis method, and the weighted median, simple mode, MR-Egger, and weighted mode were used to perform MR to reveal the causal effect of gut microbiota and IPF. The Cochrane's Q, leave-one-out, MR-Egger-intercept, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and Steiger tests were used to analyze the heterogeneity, horizontal pleiotropy, outliers, and directionality, respectively. Results IVW analysis results showed that Actinobacteria [OR=1.773, 95%CI (1.323, 2.377), P<0.001], Erysipelatoclostridium [OR=2.077, 95%CI (1.107, 3.896), P=0.023], and Streptococcus [OR=1.35, 95%CI (1.100, 1.657), P=0.004] could increase the risk of IPF. Bifidobacterium [OR=0.668, 95%CI (0.620, 0.720), P<0.001], Ruminococcus [OR=0.434, 95%CI (0.222, 0.848), P=0.015], and Tyzzerella [OR=0.479, 95%CI (0.304, 0.755), P=0.001] could reduce the risk of IPF. No significant heterogeneity, horizontal pleiotropy, outliers, and reverse causality were found. Conclusion Actinobacteria, Erysipelatoclostridium and Streptococcus may increase the risk of IPF, while Bifidobacterium, Ruminococcus and Tyzzerella may reduce the risk of IPF. Regulation of the above gut microbiota may become a new direction in the study of the pathogenesis of IPF.
5.Differences in chemical components and quality analysis of Gardenia jasminoides before and after processing with ginger
Lihua TANG ; Yu WU ; Xuedi HUANG ; Xiaolian HU ; Yi TANG ; Zilong CHEN ; Xiaofan XIAO ; Xide YE
China Pharmacy 2026;37(2):168-173
OBJECTIVE To analyze the differences in chemical components of Gardenia jasminoides before and after processing with ginger, and to evaluate the quality differences among different producing areas. METHODS Ultra-high performance liquid chromatography-tandem time-of-flight mass spectrometry was used to analyze the compositional differences of G. jasminoides before and after processing with ginger. The water content, total ash, and ethanol-soluble extract content of ginger- processed G. jasminoides were determined according to the 2020 edition of Chinese Pharmacopoeia. High performance liquid chromatography was adopted to determine the contents of genipin gentiobioside, geniposide, crocin Ⅰ and crocin Ⅱ in ginger- processed G. jasminoides. RESULTS A total of 49 chemical components were identified from raw G. jasminoides and ginger- processed G. jasminoides, including 14 flavonoids, 15 iridoids, 10 organic acids, 2 alkaloids and 8 other compounds. Among them, 42 components were detected in raw G. jasminoides, 28 in ginger-processed G. jasminoides, and 21 components were common to both. After processing with ginger, raw G. jasminoides lost 21 components (including iridoids, flavonoids, alkaloids, and others), while 7 chemical components were added (including coumarins, organic acids, organic acid esters, and flavonoids). For the 15 batches of ginger-processed G. jasminoides, the water content ranged from 5.64% to 7.11%, total ash from 2.92% to 4.87%, and ethanol-soluble extract from 40.61% to 58.02%. The average contents of genipin gentiobioside, geniposide, crocin Ⅰ and crocin Ⅱ were 0.108 7, 0.542 2, 0.565 0, and 0.012 5 mg/g, respectively. CONCLUSIONS After processing with ginger, G. jasminoides loses 21 components, while 7 new components are added. Differences are observed in the water content, total ash, ethanol-soluble extract, and the contents of genipin gentiobioside, geniposide, crocin Ⅰ, and crocin Ⅱ of ginger-processed G. jasminoides from different producing areas. Notably, samples from Fujian exhibit high contents of genipin gentiobioside and ethanol-soluble extract, while samples from Jiangxi have a high content of crocin Ⅰ.
6.Clinical Advantages of Traditional Chinese Medicine in Treatment of Childhood Simple Obesity: Insights from Expert Consensus
Qi ZHANG ; Yingke LIU ; Xiaoxiao ZHANG ; Guichen NI ; Heyin XIAO ; Junhong WANG ; Liqun WU ; Zhanfeng YAN ; Kundi WANG ; Jiajia CHEN ; Hong ZHENG ; Xinying GAO ; Liya WEI ; Qiang HE ; Qian ZHAO ; Huimin SU ; Zhaolan LIU ; Dafeng LONG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):238-245
Childhood simple obesity has become a significant public health issue in China. Modern medicine primarily relies on lifestyle interventions and often suffers from poor long-term compliance, while pharmacological options are limited and associated with potential adverse effects. Traditional Chinese Medicine (TCM) has a long history in the prevention and management of this condition, demonstrating eight distinct advantages, including systematic theoretical foundation, diversified therapeutic approaches, definite therapeutic efficacy, high safety profile, good patient compliance, comprehensive intervention strategies, emphasis on prevention, and stepwise treatment protocols. Additionally, TCM is characterized by six distinctive features: the use of natural medicinal substances, non-invasive external therapies, integration of medicinal dietetics, simple exercise regimens, precise syndrome differentiation, and diverse dosage forms. By combining internal and external treatments, TCM facilitates individualized regimen adjustment and holistic regulation, demonstrating remarkable effects in improving obesity-related metabolic indicators, regulating constitutional imbalance, and promoting healthy behaviors. However, challenges remain, such as inconsistent operational standards, insufficient high-quality clinical evidence, and a gap between basic research and clinical application. Future efforts should focus on accelerating the standardization of TCM diagnosis and treatment, conducting multicenter randomized controlled trials, and fostering interdisciplinary integration, so as to enhance the scientific validity and international recognition of TCM in the prevention and treatment of childhood obesity.
7.Effect and Mechanism of Xiao Qinglongtang Against Right Ventricular Dysfunction in Rats with Pulmonary Arterial Hypertension Induced by Monocrotaline
Lei QI ; Huifei ZHANG ; Ling GONG ; Jifu HE ; Wenjing CHEN ; Weipin NIU ; Xiao LI ; Yuehua JIANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):11-19
ObjectiveThis study aimed to establish a monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) rat model to systematically evaluate the protective effect of Xiao Qinglongtang (XQLT) on right cardiac function in model rats and further elucidate the underlying regulatory mechanism. MethodsSixty male SD rats were randomly assigned to the normal group, model group, XQLT low-, medium-, and high-dose groups (XQLT-L/M/H), and the beraprost sodium tablet group (BST). Except for the normal group, rats in all other groups were given a single subcutaneous injection of MCT (60 mg·kg-1) to induce PAH. Three weeks after injection, rats in the XQLT-L/M/H groups were administered XQLT intragastrically at 3.07, 6.14, 12.28 g·kg-1·d-1, respectively. Rats in the BST group received beraprost sodium at 12.6 μg·kg-1·d-1, and rats in the model group received an equal volume of saline. All treatments lasted for 3 weeks. Right ventricular systolic pressure (RVSP) was measured by right ventricular catheterization. Cardiac function was assessed by echocardiography. The right ventricle was weighed to calculate the right ventricular hypertrophy index (RVHI). Hematoxylin-eosin (HE) staining, Masson staining, and transmission electron microscopy were used to observe myocardial morphology. Serum metabolomic changes were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Data-independent acquisition (DIA) proteomics was used to detect differentially expressed (DE) proteins in the right ventricle, and Western blot was used to measure the expression of uncoupling protein 3 (UCP3), phosphatidylinositol 3-kinase catalytic subunit p110α (PIK3CA), L1 cell adhesion molecule (L1CAM), and quinone oxidoreductase (CRYZ). UPLC-MS/MS was used to analyze the chemical components of XQLT. ResultsCompared with the normal group, the model group showed significantly increased RVSP and RVHI (P<0.05), along with pathological changes in myocardial morphology. Compared with the model group, all XQLT-treated groups exhibited reductions in RVSP and RVHI as well as significant improvements in cardiac function and myocardial morphology. Among the XQLT groups, XQLT-M showed the most pronounced effects (P<0.05), comparable to the BST group. Serum metabolomics revealed 105 differential metabolites in the XQLT groups versus the model group [variable importance in projection (VIP) >1, P<0.05], including 58 upregulated and 47 downregulated metabolites. KEGG enrichment analysis indicated that XQLT intervention downregulated phenylalanine metabolism (P<0.01) and upregulated unsaturated fatty acid biosynthesis (P<0.05). Proteomics analysis showed that 982 DE proteins were identified in the MCT groups versus the normal group, including 455 upregulated and 527 downregulated proteins (|fold change (FC)| >1.3, P<0.05). Compared with the model group, 237 DE proteins were identified in the XQLT groups, including 124 upregulated and 113 downregulated proteins (|FC| >1.3, P<0.05), with 57 overlapping DE proteins. KEGG enrichment suggested that XQLT mainly modulated pathways related to mineral absorption, ribosomal biogenesis, peroxisomes, glycolysis/gluconeogenesis, spliceosomes, and thyroid hormone signaling. Western blot analysis showed that, compared with the model group, XQLT increased the expression of UCP3, PIK3CA, and L1CAM, while decreasing the expression of CRYZ (P<0.05). ConclusionXQLT exerts a protective effect on right heart function in MCT-induced PAH rats, and its mechanism is associated with maintaining myocardial homeostasis and alleviating right ventricular remodeling.
8.Mechanism of action of Qingre huatan huoxue decoction against atherosclerosis based on macrophage polarization
Huaping ZHONG ; Qicheng ZHU ; Zhengwei ZOU ; Zhengyi HE ; Heping XIE ; Xu CHEN ; Zhisheng DUAN ; Tian XIAO
China Pharmacy 2026;37(4):438-443
OBJECTIVE To explore the mechanism of action of Qingre huatan huoxue decoction against atherosclerosis (AS)based on macrophage polarization. METHODS Using atorvastatin served as the positive control, the drug-containing serum of the Qingre huatan huoxue decoction was prepared to treat RAW264.7 macrophages. Macrophage viability, apoptosis rate, and the fluorescence intensities of CD86 and CD206 were measured, along with the levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Apolipoprotei n E-deficient (ApoE -/- ) mice (AS model mice) fed with a high-fat diet were randomly assigned to model group, atorvastatin group (2.6 mg/kg), and low-, medium- and high-dose groups of Qingre huatan huoxue decoction (90, 180, 360 mg/kg), respectively. C57BL/6J mice fed with a standard diet served as the normal control group, with 10 mice per group. The treatment group mice were administered the corresponding drugs intragastrically, once daily, for 8 consecutive weeks. Serum levels of TNF-α and IL-1β were measured in all groups. Lipid deposition in the aorta (assessed by the percentage of plaque in the entire aorta and aortic root) and morphological changes in the aortic root were observed. Expression levels of CD86 and CD206 in aortic tissue, as well as the protein expression levels of inducible nitric oxide synthase (iNOS), arginase-1 (Arg-1), AMP-activated protein kinase (AMPK), phosphorylated AMPK (p-AMPK), and peroxisome proliferator-activated receptor γ (PPAR-γ) in aortic tissues were all detected. RESULTS Cell experiment results showed that, at concentrations of 5-100 μg/mL, the drug-containing serum of the Qingre huatan huoxue decoction significantly increased RAW264.7 cell viability ( P <0.05). The drug-containing serum of the Qingre huatan huoxue decoction at concentrations of 10, 50, and 100 μg/mL, along with atorvastatin, significantly reduced apoptosis rates, CD86 fluorescence intensity, and TNF-α and IL-1β levels in RAW264.7 cells, while markedly enhancing CD206 fluorescence intensity ( P <0.05). Animal experiment results showed that, compared with the model group, all dosage groups of Qingre huatan huoxue decoction and the atorvastatin group showed significantly reduced/down-regulated levels of TNF-α and IL-1β in serum, along with decreased aortic total and root plaque percentages, CD86 expression, and iNOS protein expression. CD206 expression and Arg-1, p-AMPK/AMPK, PPAR-γ protein expression were significantly up-regulated ( P <0.05). Pathological morphology of the aorta showed varying degrees of improvement. CONCLUSIONS The formula of Qingre huatan huoxue decoction exerts its anti-AS effects by regulating macrophage polarization, increasing the proportion of M2 macrophages, thereby effectively inhibiting AS plaque formation and reducing inflammatory responses.
9.Zuogui Wan Improve Ovarian Inflammatory Microenvironment and Stemness of Ovarian Germline Stem Cells in Ovarian Aging via cGAS/STING Signaling Pathway
Yunling ZHENG ; Xinyi PAN ; Zuang LI ; Yixuan WANG ; Junyi AN ; Yuxin ZOU ; Mengting XIAO ; Zheng CHEN ; Ling ZHU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):1-10
ObjectiveTo investigate the mechanism of Zuogui Wan (ZGW) in improving ovarian inflammatory microenvironment and stemness of ovarian germline stem cells (OSCs) for treating ovarian aging via the cyclic guanosine monophosphate/adenosine monophosphate synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway. MethodsForty C57BL/6 female mice were randomly divided into a blank group, a model group, a low-dose ZGW group (2.7 g·kg-1), a high-dose ZGW group (5.4 g·kg-1), and an estradiol valerate group (0.15 mg·kg-1), with 8 mice in each group. Except the blank group, all other groups received a single intraperitoneal injection of cyclophosphamide at 120 mg·kg-1 to establish an ovarian aging mouse model. After successful modeling, each group was continuously administered for 4 weeks, once daily. The physiological status of the mice was observed, and the ovarian index was calculated. The estrus cycle of the mice was monitored. Hematoxylin-eosin (HE) staining was used to observe pathological changes in ovarian tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum sex hormone levels. Serum inflammatory factors interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and mouse interleukin-6 (IL-6) levels were detected using kits. Western blot was used to detect the protein expression of ovarian cGAS, STING, p-STING, TANK-binding kinase 1 (TBK1), p-TBK1, interferon-induced transmembrane protein 3 (Fragilis), and Vasa homolog protein (MVH). Quantitative real-time polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of inflammatory factors in ovarian tissue. Immunofluorescence double labeling was performed to locate OSCs in ovarian tissues, and fluorescence intensities of OSCs markers MVH and octamer binding transcription factor 4 (Oct4) were calculated. ResultsCompared with the blank group, the model group showed reduced body weight, ovarian wet weight, and ovarian index (P<0.01) and a disordered estrus cycle (P<0.01). In addition, the levels of serum follicle-stimulating hormone (FSH), TNF-α, IL-6, and IL-1β were increased (P<0.01), while anti-Müllerian hormone (AMH) and estradiol (E2) levels were decreased (P<0.01). The protein expression of cGAS, p-STING/STING, and p-TBK1/TBK1 in ovarian tissue was increased (P<0.05, P<0.01), while that of OSCs stemness factors MVH and Fragilis was reduced (P<0.01). Immunofluorescence indicated a reduction in MVH and Oct4 expression in OSCs (P<0.01). The mRNA expression of inflammatory factors TNF-α, IL-6, and IL-1β in ovarian tissue was increased (P<0.05, P<0.01). Compared with the model group, the treatment groups exhibited improved body weight, ovarian wet weight, and ovarian index (P<0.05) and a reduced rate of estrus cycle disorder (P<0.05, P<0.01). The levels of serum FSH, TNF-α, IL-6, and IL-1β were decreased (P<0.05, P<0.01), while AMH and E2 levels were increased (P<0.01). The protein expression levels of cGAS, p-STING/STING, and p-TBK1/TBK1 in ovarian tissue were decreased (P<0.05), while the protein expression of MVH and Fragilis was increased (P<0.05), and the fluorescence intensities of MVH and Oct4 were increased (P<0.05, P<0.01). The mRNA expression of inflammatory factors in ovarian tissue was decreased (P<0.05). ConclusionZGW alleviate ovarian inflammatory response, regulate ovarian microenvironment homeostasis, and maintain stemness of OSCs in ovarian aging mice probably by modulating the cGAS-STING signaling pathway, thereby improving ovarian function and delaying ovarian aging.
10.Pathogenesis Evolution and Stage-based Treatment of Gout: An Exploration Based on Theory of ''Endogenous Dampness Leading to Bi Syndrome''
Yingjie ZHANG ; Fan YANG ; Ruifang YANG ; Zhuoming ZHENG ; Siwei PENG ; Yan XIAO ; Peng CHEN ; Youxin SU ; Jiemei GUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):74-83
Gout is a crystal-associated arthropathy caused by the deposition of monosodium urate crystals and is closely related to purine metabolic disorders and impaired uric acid excretion. It is clinically characterized by hyperuricemia, recurrent joint swelling and pain, and tophus formation. The disease course is divided into three stages: The hyperuricemia stage, acute attack stage, and chronic gouty arthritis stage. Modern medicine has reached a consensus on its pathology, but traditional Chinese medicine (TCM) lacks a systematic stage-specific understanding of gout pathogenesis and its underlying mechanisms, making it difficult to guide precise syndrome differentiation and treatment. By integrating classical TCM theory, clinical practice, and modern medical understanding, and drawing upon descriptions of Bi syndrome caused by endogenous dampness and turbidity in classical texts such as Huangdi Neijing·Ling Shu and Synopsis of the Golden Chamber, our team proposes the pathogenic concept of gout as ''endogenous dampness leading to Bi syndrome'' and the core pathogenesis of ''spleen deficiency with internal retention of dampness-turbidity''. We systematically elucidate the evolution of pathogenesis across different stages and corresponding therapeutic strategies. This study posits that metabolic byproducts such as urate fall under the category of ''endogenous pathogenic dampness-turbidity''. When genetic or dietary factors lead to metabolic abnormalities, it manifests as ''spleen deficiency with impaired transport and transformation'', resulting in ''internal retention of pathogenic dampness-turbidity''. When damp-turbidity stagnates in the blood vessels, serum uric acid levels rise. When it stagnates in the viscera and limbs, monosodium urate crystals deposit in the joints. Triggered by precipitating factors, this leads to gout attacks—the core pathological process of ''endogenous dampness leading to Bi syndrome''. Based on this theory, the stage-specific pathogenic characteristics of gout are proposed: The hyperuricemia stage is characterized by ''spleen deficiency with impaired transport and transformation, internal retention of pathogenic dampness-turbidity'', the acute attack stage is primarily marked by ''dampness-turbidity and static heat obstructing the limbs and joints'', while the chronic stage is defined by ''spleen deficiency with internal retention of pathogenic dampness-turbidity, intermingled with phlegm-stasis binding''. The treatment principle centers on ''strengthening the spleen and draining dampness'' throughout all stages. During the hyperuricemia stage, treatment focuses on ''strengthening the spleen, draining dampness, and eliminating turbidity''. In the acute attack stage, the treatment should "strengthen the spleen, drain dampness, clear heat, eliminate turbidity, alleviate swelling, and relieve pain''. In the chronic stage, the treatments emphasizes to ''strengthen the spleen, drain dampness, transform turbidity, clear heat, resolve phlegm, and activate blood circulation''. This approach has yielded favorable therapeutic outcomes in clinical practice. This theoretical system clarifies the nature of gout as ''spleen deficiency being the root, dampness-turbidity being the secondary manifestation'' and systematically analyzes its pathogenesis evolution process and characteristics. The constructed stage-based treatment protocol has been validated through clinical and basic research, providing systematic theoretical guidance and a practical framework for the precise TCM management of gout, thereby promoting the modernization of TCM pathogenesis theory related to gout.

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