1.Olfactory Receptors Expressed in The Intestine and Their Functions
Pei-Wen YANG ; Meng-Meng YUAN ; Ying ZHOU ; Peng LI ; Gui-Hong QI ; Ying YANG ; Zhong-Yi MAO ; Meng-Sha ZHOU ; Xiao-Shuang MAO ; Jian-Ping XIE ; Yi-Nan YANG ; Shi-Hao SUN
Progress in Biochemistry and Biophysics 2026;53(3):534-549
Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.
2.Proteomic Analysis of Danlou Tablet in Improving Platelet Function for Treating Coronary Heart Disease with Phlegm-stasis Intermingling Syndrome in Minipigs
Ziyan WANG ; Ying LI ; Aoao WANG ; Hongxu MENG ; Yue SHI ; Yanlei MA ; Guoyuan ZHANG ; Lei LI ; Jianxun LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):41-53
ObjectiveThis paper aims to observe the role of Danlou tablet in treating coronary heart disease (CHD) with phlegm-stasis intermingling syndrome in minipigs by improving platelet function and explore the potential pharmacological mechanism of Danlou tablet in regulating platelet function by using proteomics technology. MethodsThirty Bama minipigs were randomly divided into a normal control group (6 pigs) and a high-fat diet group (24 pigs). After 2 weeks of high-fat diet feeding, the high-fat diet group was randomly subdivided into a model group, an atorvastatin group (1 mg·kg-1), and Danlou tablet groups (0.6 g·kg-1 and 0.3 g·kg-1). All groups continued to receive a high-fat diet for 8 weeks after the procedure. The normal control group was given a regular diet, underwent only coronary angiography, and did not receive an interventional injury procedure. The model group and each administration group were fed a high-fat diet. Two weeks later, they underwent a coronary angiography injury procedure. After the procedure, drugs were mixed into the feed every morning for 8 consecutive weeks, with the minipigs maintained on a continuous high-fat diet during this period. Quantitative proteomics technology was further used to study platelet proteins, and differential proteins were obtained by screening. Bioinformatics analysis was performed to analyze key regulatory proteins and biological pathways involved in the therapeutic effect of Danlou tablet on CHD with phlegm-stasis intermingling syndrome. ResultsCompared with the normal control group, the model group showed a significant increase in total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) of minipigs' serum (P<0.01), a significant shortening in prothrombin time of (PT) (P<0.01), a coagulation function index, and an increase in whole blood viscosity (P<0.01) and platelet aggregation rate (P<0.01). Moreover, the platelet morphology was altered, and the contents of endothelin-1 (ET-1) and nitric oxide (NO) were significantly increased (P<0.01). Hemodynamic parameters were obviously abnormal, including significantly decreased systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), and left ventricular maximal positive dp/dt (LV+dp/dtmax) (P<0.01). Left ventricular maximal negative dp/dt (LV-dp/dtmax) was significantly increased (P<0.01). Besides, there were myocardial cell hypertrophy, obvious edematous degeneration, massive interstitial inflammatory cell infiltration, high degree of fibrosis, and coronary endothelial atherosclerosis. TC and TG levels in minipigs' serum were significantly reduced in Danlou tablet groups with 0.6 g·kg-1 and 0.3 g·kg-1 (P<0.05, P<0.01), compared with those in the model group. LDL-C was decreased in the Danlou tablet group with 0.6 g·kg-1 (P<0.05). The whole blood viscosity under low and high shear conditions was significantly reduced in the Danlou tablet group with 0.6 g·kg-1 (P<0.05). In groups with all doses of Danlou tablet, maximum aggregation rate (MAR) and average aggregation rate (AAR) were significantly decreased (P<0.05, P<0.01), and platelets' morphological changes such as pseudopodia extension were reduced. ET-1 levels in the serum were significantly reduced. In the Danlou tablet group with 0.6 g·kg-1, NO level in the serum was reduced (P<0.05). In groups with all doses of Danlou tablet, DBP and MAP were significantly increased (P<0.05). In the Danlou tablet group with 0.6 g·kg-1, LVSP and LV+dp/dtmax were significantly increased (P<0.05, P<0.01), and LV-dp/dtmax was significantly decreased (P<0.05). In groups with all doses of Danlou tablet, edematous degeneration in myocardial tissue was milder, and coronary artery lesion degree was significantly alleviated. Compared with the normal control group, there were 94 differentially expressed proteins in the model group, including 81 up-regulated and 13 down-regulated proteins. Compared with the model group, the Danlou tablet group with 0.6 g·kg-1 showed 174 differentially expressed proteins, including 100 up-regulated and 74 down-regulated proteins. A total of 30 proteins were reversed after Danlou tablet intervention. Bioinformatics analysis revealed that its pharmacological mechanism may exert anti-platelet activation, aggregation, and adhesion effects through biological pathways such as regulation of actin cytoskeleton, platelet activation pathway, Fcγ receptor-mediated phagocytosis, as well as proteins such as growth factor receptor-bound protein 2 (GRB2), Ras-related C3 botulinum toxin substrate 2 (RAC2), RAC1, and heat shock protein 90 alpha family class A member 1 (HSP90AA1). ConclusionDanlou tablet can effectively reduce platelet activation and aggregation, exerting a good therapeutic effect on CHD with phlegm-stasis intermingling syndrome in minipigs. Its pharmacological mechanism may involve regulating biological pathways such as actin cytoskeleton and platelet activation pathway, as well as proteins like GRB2, RAC2, RAC1, and HSP90AA1, thereby exerting a pharmacological effect in anti-platelet activation, aggregation, and adhesion.
3.Research progress on strategies for toxicity reduction and efficacy enhancement of triptolide
Xiaoqing ZHENG ; Ying DING ; Shanshan XU ; Long WANG ; Shanshan HAN ; Yaping XING ; Meng ZHANG ; Wenhao LI
China Pharmacy 2026;37(11):1496-1501
Triptolide (TP), the core active component of the traditional Chinese medicine Tripterygium wilfordii , exhibits remarkable pharmacological activities including anti-inflammatory, immunosuppressive and anti-tumor effects, and holds broad application prospects in the treatment of major diseases such as autoimmune diseases and malignant tumors. However, TP has a narrow therapeutic window and causes multi-organ toxicities including liver, kidney and reproductive toxicities, which severely restrict its safe clinical application and new drug development. Therefore, toxicity reduction and efficacy enhancement has become a core scientific problem urgently to be solved in this field. This paper systematically reviews the four core strategies for TP toxicity reduction and efficacy enhancement, including structural modification, dosage form improvement, herbal compatibility, and external therapies of traditional Chinese medicine. Among them, structural modification optimizes the toxic and efficacy characteristics of TP from the molecular structure level, with typica l derivatives including (5 R )-5-hydroxy triptolide, ZT01, PG490-88, etc. Dosage form modification achieves toxicity reduction and efficacy enhancement via targeted and sustained-controlled drug release of diverse delivery systems. It includes triptolide preparations such as nanoparticles, liposomes, microemulsion gels and liquid crystals, possessing favorable clinical transformation potential. The herbal compatibility and external therapies of traditional Chinese medicine conform to the holistic view of traditional Chinese medicine and have a profound clinical application foundation, but their mechanisms of action are insufficiently elucidated, and they lack unified standardized specifications and high-quality evidence-based proof. In the future, we should rely on multi-omics technology to elucidate the toxic and efficacy mechanisms, integrate technologies to optimize preparations, improve the evaluation system and promote clinical transformation.
4.Blood donation in hypertensive populations: risk mechanisms, international practices, and future perspectives
Lizhou ZHAO ; Meng LI ; Ying LI ; Xue CHEN ; Kefen WANG ; Yishu WANG ; Xuemei FU
Chinese Journal of Blood Transfusion 2026;39(6):799-808
Hypertension ranks among the most prevalent chronic non-communicable diseases worldwide, with its prevalence rising steadily and exerting substantial impacts on the demographic composition of voluntary blood donors and the safety of blood supply. The eligibility of hypertensive individuals for safe blood donation and the relevant screening and management strategies have long remained controversial in transfusion medicine. This article systematically reviews the epidemiological characteristics of hypertension, donation-related physiological alterations and underlying risk mechanisms. By synthesizing evidence from international multicenter studies and regulatory practices across major nations, it conducts a comprehensive analysis of blood donation safety and donor admission criteria for hypertensive patients. Available evidence demonstrates that for hypertensives with well-stabilized blood pressure and no severe cardiac, cerebral or renal complications or target organ damage, the overall incidence of adverse reactions following blood donation is comparable to that in healthy donors, and no definitive correlation has been identified between blood pressure levels and vasovagal responses. Current mainstream international management frameworks are gradually shifting from screening reliant on a single blood pressure cutoff value toward an integrated strategy combining stratified risk classification and individualized dynamic assessment, with core focus on long-term blood pressure control, consistency of medication regimens and complication status. Meanwhile, emerging technologies including artificial intelligence, ambulatory blood pressure monitoring and wearable devices have opened innovative avenues for blood donation risk evaluation and full-cycle donor management. In light of existing clinical evidence, future efforts should further refine the multi-dimensional risk stratification system, facilitate the implementation of intelligent screening and continuous monitoring technologies, and scale up health education and follow-up management for hypertensive populations. Such measures aim to appropriately expand the pool of eligible blood donors while safeguarding donation safety, ultimately achieving coordinated improvement in blood safety and blood supply capacity.
5.Regulatory effect of Shugan Yunpi Decoction on depressive and anxiety symptoms in colorectal cancer patients with depressive disorder based on the PI3K-AKT signaling pathway
Jing MENG ; Jingman ZHAO ; Fang TIAN ; Dong WEI ; Hairu YU ; Chaonan FENG ; Yanan LI ; Ying YANG
Sichuan Mental Health 2026;39(4):324-330
BackgroundPatients with colorectal cancer are frequently comorbid with depression, which severely affects the quality of life and treatment compliance, while compromising the efficacy of anticancer treament and prognosis. Current therapeutic strategies still have notable limitations, particularly the lack of systematic and targeted synergistic regimens that integrate oncological management and anti-depressive intervention. It is of great clinical significance to explore a safe and effective new comprehensive intervention protocol and clarify its underlying mechanism of action. ObjectiveTo explore the effectiveness and safety of Shugan Yunpi Decoction in alleviating depressive and anxiety symptoms in colorectal cancer patients with depressive disorder through the PI3K-AKT signaling pathway, in order to provide references for the comprehensive treatment of colorectal cancer and depressive disorder. MethodsThis study was a randomized controlled trial. A total of 106 patients admitted to the Baoding No.1 Hospital of traditional Chinese medicine from November 2023 to July 2025 were enrolled, who met the diagnostic criteria for the Chinese protocol of diagnosis and treatment of colorectal cancer (2023 edition) and the diagnostic criteria for depressive disorder as specified in the Chinese Classification and Diagnostic Criteria of Mental Disease, third edition (CCMD-3). Patients were divided into the study group and the control group using a random number table, with 53 cases in each group. The control group received conventional chemotherapy combined with traditional Chinese medicine five-element music therapy, while the study group received conventional chemotherapy combined with Shugan Yunpi Decoction therapy. Both groups were treated for 8 weeks. Depressive and anxiety symptoms were assessed using the Hamilton Depression Scale-17 item(HAMD-17) and Hamilton Anxiety Scale (HAMA), respectively. Western blot protein immunoblotting was used to detect the expression levels of PI3K, AKT, and pAKT. Real-time fluorescence quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression levels of PI3K mRNA and AKT mRNA. Adverse reactions were recorded using a self-designed adverse reaction record form. ResultsRepeated measures analysis of variance showed that the time effects (F=139.336, 234.747), group effects (F=43.900, 101.266), and time-group interaction effects (F=13.409, 43.216) for HAMD-17 and HAMA scores in both groups were statistically significant (P<0.01). After 4 and 8 weeks of treatment, the HAMD-17 and HAMA scores in both groups were lower than those before treatment, with statistically significant differences (P<0.05). HAMD-17 and HAMA scores in the study group were lower than those in the control group (P<0.05). The time effects (F=571.356, 309.266, 414.492), group effects (F=6.901, 26.361, 39.362), and time-group interaction effects (F=18.592, 19.266, 33.484) for the protein expression levels of PI3K, AKT, and pAKT in both groups were all statistically significant (P<0.01). After 8 weeks of treatment, the protein expression levels of PI3K and pAKT in the study group were lower than those in the control group, while the AKT protein expression level was higher than that in the control group(P<0.01). The time effects (F=338.555, 225.059), group effects (F=5.429, 9.726), and time-group interaction effects (F=12.953, 21.214) for PI3K mRNA and AKT mRNA expression levels in two groups were all statistically significant (P<0.01). After 8 weeks of treatment, the expression levels of PI3K mRNA and AKT mRNA in the study group were lower than those in the control group (P<0.05). The incidence of adverse reactions in the study group was lower than that in the control group (χ2=4.810, P<0.05). ConclusionShugan Yunpi Decoction may help to ameliorate depressive and anxiety symptoms in colorectal cancer patients with depressive disorder by regulating the PI3K-AKT signaling pathway, decreasing the levels of PI3K, pAKT, PI3K mRNA, and AKT mRNA, with a favorable safety profile. [Funded by Baoding City Science and Technology Planning Project (number, 2341ZF291)]
6.Safety evaluation of therapeutic plasma exchange in patients with lower hematocrit levels
Ying LI ; Yuanming YANG ; Zifan MENG ; Zheng LIU ; Haiyan WANG
Chinese Journal of Blood Transfusion 2025;38(5):699-703
Objective: To retrospectively assess whether a lower hematocrit level (between 18% and 20%) had any impact on the safety of patients undergoing therapeutic plasma exchange (TPE), and to further determine the threshold for red blood cell supplementation prior to TPE. Methods: Clinical data from 181 adult patients who underwent TPE treatment at the Department of Blood Transfusion of our hospital from March 2023 to July 2024 were collected. The patients were divided into a study group of 44 patients (Hct ≥18% and <20%) and a control group of 137 patients (Hct≥20%). In two groups, blood volume-related safety indicators including respiration rate, heart rate, systolic blood pressure, and blood oxygen saturation levels before and after TPE were compared using t-test. Between-group differences in the grading of adverse reactions such as allergies and hypotension were analyzed using chi-square test. Results: A total of 659 TPE treatments were performed on 181 patients, with 169 TPE treatments on 44 patients in the study group (Hct≥18% and <20%) and 490 TPE treatments on 137 patients in the control group (Hct≥20%). There were no statistically significant differences in age, gender, BMI category, and the presence of cardiac insufficiency between the two groups. In the study group, there were no statistically significant differences in safety indicators such as respiration rate, heart rate, systolic blood pressure, and blood oxygen saturation level before and after TPE. In the control group, there were no statistically significant differences in heart rate and systolic blood pressure before and after TPE, but there were statistically significant differences in respiration rate and blood oxygen saturation level (P<0.05). There were no statistically significant differences in the grading of adverse reactions such as allergic reactions and hypotension between the two groups. Conclusion: For adult patients with stable conditions, maintaining a lower hematocrit level (Hct ≥18% and <20%) during TPE is relatively safe. It is feasible to lower the TPE red blood cell supplementation threshold to 18%≤Hct<20%,which may save blood resources while potentially benefit patients by avoiding unnecessary red blood cell transfusion.
7.Manufacture and mechanical property on zirconia abutments with a titanium base in dental implant restoration
Huan WANG ; Jing LU ; Ying LI ; Maohua MENG ; Jiayu SHU ; Yuncai LUO ; Wenjie LI ; Qiang DONG
Chinese Journal of Tissue Engineering Research 2025;29(10):2171-2177
BACKGROUND:With the development of computer-aided design and computer-aided manufacturing technology,zirconia abutments with a titanium base are widely used in clinic due to its good application advantages,but there are still some problems and a lack of consensus design standards. OBJECTIVE:To review the fabrication methods of Ti-base zirconia abutment,and the effect of abutment connection,emergence design,abutment angle,and bonding on mechanical properties of Ti-base zirconia abutment. METHODS:Relevant literature published from 2010 to 2023 was searched in CNKI and PubMed databases with the search terms"zirconia abutment,titanium base"in Chinese and English,respectively.The search time limit was extended for some classical literature.The relevant literature was obtained through inclusion and exclusion criteria,and 57 eligible documents were included for review. RESULTS AND CONCLUSION:It is recommended that clinicians try to select antirotational titanium bases or rotational titanium bases with a Morse taper connection.Implants should be placed in the correct axial angulation of not more than 15° or with an inclination to the palatal side when using angled zirconia abutments.When a≥30° labial inclination is followed for implant placement,the bite force must be decreased effectively to reduce the risk of mechanical and biological complications of implants,abutments,and prostheses.Ti-base zirconia abutments with a higher gingival height should be selected,and its restorative angle should not exceed 40°.Multilink Hybrid Abutment could be the first choice for extraoral bonding of zirconia abutment to titanium bases.
8.Ameliorating effects of tetrahydrocurcumin and its nano-preparations on lipopolysaccharide-induced depression in mice
Hui Tan ; Yuanping Li ; Jingyuan Meng ; Tengteng Ma ; Yan Yang ; Zhengmao Yang ; Jiaqing Ma ; Jianping Xie ; Ying Guo
Acta Universitatis Medicinalis Anhui 2025;60(1):79-86
Objective :
To investigate the antidepressant effects and the underlying mechanisms of tetrahydrocurcumin(THC) and its nanoparticle formulation(THCN).
Methods :
Forty-six male ICR mice were randomly divided into Con group, LPS group, THC group, THCN group and SER group. A mouse depression model was established by intraperitoneal administration of LPS. The anxiety and depression-like behaviors of mice were evaluated by open field test(OFT) and forced swimming test(FST). Myelin staining was applied to assess the extent of demyelination in the prefrontal cortex of the mice. The prefrontal cortex and hippocampus were further examined for the expression levels of glial fibrillary acidic protein(GFAP) and Toll-like receptor 4(TLR4) through quantitative immunofluorescence assays.
Results :
Compared with the Con group, the LPS group showed increased anxiety-like and depressive-like behaviors in both the long-term and short-term experiments(P<0.05); the degree of demyelination increased in the LPS group of the long-term experiment(P<0.01); the expression of GFAP was reduced in the LPS group of the short-term experiment(P<0.01), while the expression of TLR4 increased(P<0.05); the expression of TLR4 decreased in the THC group(P<0.01); the expression of GFAP in the prefrontal cortex of the THCN group was reduced(P<0.01), while the expression of TLR4 increased(P<0.05). Compared with the LPS group, the THC group showed reduced depressive-like behaviors in the long-term experiment(P<0.05), while the anxiety-like and depressive-like behaviors of the THCN group and the SER group were reduced(P<0.05), and the anxiety-like and depressive-like behaviors of the THC group and the THCN group were reduced in the short-term experiment(P<0.05); the degree of demyelination was reduced in the THC group, THCN group and SER group in the long-term experiment(P<0.05); the expression of GFAP increased in the THC group of the short-term experiment(P<0.05), while the expression of TLR4 was reduced(P<0.05), and the expression of GFAP increased in the THCN group(P<0.05). Compared with the THC group, the THCN group and the SER group showed reduced anxiety-like behaviors in the long-term experiment(P<0.05); the expression of GFAP in the prefrontal cortex of the THCN group was reduced in the short-term experiment(P<0.05), while the expression of TLR4 in the hippocampal DG area increased in the short-term experiment(P<0.01).
Conclusion
Tetrahydrocurcumin and its nanoparticle formulation both exert significant ameliorative effects on depression-like behaviors and demyelination in mice induced by lipopolysaccharide. The antidepressant mechanism of THC appears to be mediated through the down-regulation of TLR4 and the up-regulation of GFAP. The mechanism underlying the antidepressant action of THCN seems predominantly focused on the enhancement of GFAP expression.
9.Glucocorticoid Discontinuation in Patients with Rheumatoid Arthritis under Background of Chinese Medicine: Challenges and Potentials Coexist.
Chuan-Hui YAO ; Chi ZHANG ; Meng-Ge SONG ; Cong-Min XIA ; Tian CHANG ; Xie-Li MA ; Wei-Xiang LIU ; Zi-Xia LIU ; Jia-Meng LIU ; Xiao-Po TANG ; Ying LIU ; Jian LIU ; Jiang-Yun PENG ; Dong-Yi HE ; Qing-Chun HUANG ; Ming-Li GAO ; Jian-Ping YU ; Wei LIU ; Jian-Yong ZHANG ; Yue-Lan ZHU ; Xiu-Juan HOU ; Hai-Dong WANG ; Yong-Fei FANG ; Yue WANG ; Yin SU ; Xin-Ping TIAN ; Ai-Ping LYU ; Xun GONG ; Quan JIANG
Chinese journal of integrative medicine 2025;31(7):581-589
OBJECTIVE:
To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM).
METHODS:
This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis.
RESULTS:
Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings.
CONCLUSIONS
RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult
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Aged
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Female
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Humans
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Male
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Middle Aged
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Arthritis, Rheumatoid/drug therapy*
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Glucocorticoids/therapeutic use*
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Medicine, Chinese Traditional
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Retrospective Studies
10.Danggui Shaoyaosan Regulates Nrf2/SLC7A11/GPX4 Signaling Pathway to Inhibit Ferroptosis in Rat Model of Non-alcoholic Fatty Liver Disease
Xinqiao CHU ; Yaning BIAO ; Ying GU ; Meng LI ; Tiantong JIANG ; Yuan DING ; Xiaping TAO ; Shaoli WANG ; Ziheng WEI ; Zhen LIU ; Yixin ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):35-42
ObjectiveTo investigate the effect of Danggui Shaoyaosan on ferroptosis in the rat model of non-alcoholic fatty liver disease (NAFLD) and explore the underlying mechanism based on the nuclear factor E2-related factor 2 (Nrf2)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway. MethodsThe sixty SD rats were randomly grouped as follows: control, model, Yishanfu (0.144 g·kg-1), and low-, medium-, and high-dose (2.44, 4.88, and 9.76 g·kg-1, respectively) Danggui Shaoyaosan. A high-fat diet was used to establish the rat model of NAFLD. After 12 weeks of modeling, rats were treated with corresponding agents for 4 weeks. Then, the body weight and liver weight were measured, and the liver index was calculated. At the same time, serum and liver samples were collected. The levels or activities of total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and Fe2+ in the serum and TC, TG, free fatty acids (FFA), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX), and Fe2+ in the liver were measured. Hematoxylin-eosin staining and oil red O staining were employed to observe the pathological changes in the liver. Immunofluorescence was used to assess the reactive oxygen species (ROS) content in the liver. Mitochondrial morphology was observed by transmission electron microscopy. The protein levels of Nrf2, SLC7A11, GPX4, transferrin receptor 1 (TFR1), and divalent metal transporter 1 (DMT1) in the liver were determined by Western blot. ResultsCompared with the control group, the model group showed increases in the body weight, liver weight, liver index, levels or activities of TC, TG, ALT, AST, and Fe2+ in the serum, levels of TC, TG, FFA, MDA, Fe2+, and ROS in the liver, and protein levels of TFR1 and DMT1 in the liver (P<0.01), and decreases in the activities of SOD, GPX and the protein levels of Nrf2, SLC7A11, and GPX4 in the liver (P<0.05, P<0.01). Meanwhile, the liver tissue in the model group presented steatosis, iron deposition, mitochondrial shrinkage, and blurred or swollen mitochondrial cristae. Compared with the model group, all doses of Danggui Shaoyaosan reduced the body weight, liver weight, liver index, levels or activities of TC, TG, ALT, AST, and Fe2+ in the serum, levels of TC, TG, FFA, MDA, Fe2+, and ROS in the liver, and protein levels of TFR1 and DMT1 in the liver (P<0.01), while increasing the activities of SOD and GPX and the protein levels of Nrf2, SLC7A11, and GPX4 in the liver (P<0.01). Furthermore, Danggui Shaoyaosan alleviated steatosis, iron deposition, and mitochondrial damage in the liver. ConclusionDanggui Shaoyaosan may inhibit lipid peroxidation and ferroptosis by activating the Nrf2/SLC7A11/GPX4 signaling pathway to treat NAFLD.


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