Ethnopharmacological relevance Huangqin Qingre Chubi Capsule (HQC), a hospital preparation derived from the Jianpi Qingre Tongluo formula, has demonstrated therapeutic efficacy in ankylosing spondylitis (AS). However, its underlying mechanisms, particularly in relation to patient self-perception and the lncRNA AP005432.1/PI3K/AKT signaling axis, remain unclear. Purpose This study aimed to investigate the association between HQC exposure and improvements in self-perception of patients (SPP) and immune-inflammatory markers in individuals with AS. In addition, in vitro experiments were conducted to determine whether HQC attenuates inflammatory responses through modulation of the lncRNA AP005432.1/PI3K/AKT signaling pathway. Methods A retrospective analysis of 189 hospitalized patients with AS was performed to evaluate changes in SPP (SF-36, VAS, SAS, and SDS scores) and immune-inflammatory indicators before and after HQC treatment. Analysis of covariance (ANCOVA) was applied to adjust for age, sex, disease duration, concomitant medications, and comorbidities, with Bonferroni correction for multiple comparisons. Sensitivity analyses, including additional adjustment for height and weight and exclusion of biologic DMARD (bDMARD) users, were conducted to assess the robustness of the findings. Among the cohort, 20 patients with AS treated with HQC and 20 healthy controls were selected for molecular validation of lncRNA AP005432.1 expression and cytokine levels. In vitro experiments employed a co-culture model of peripheral blood mononuclear cells (PBMCs) from patients with AS and fibroblast-like synoviocytes (FLSs). The effects of HQC-containing serum, lncRNA AP005432.1 knockdown or overexpression, and PI3K/AKT pathway modulation on cell viability, inflammatory cytokines (TNF-α, IL-6, IL-17, IL-10), and pathway-related proteins (p-PI3K and p-AKT) were assessed using CCK-8 assays, ELISA, RT-qPCR, and Western blot analyses. Results Clinical observations demonstrated that HQC exposure was significantly associated with improvements in SPP scores and reductions in inflammatory markers, including ESR, Hs-CRP, and NLR. These associations remained significant after full adjustment for confounders and across sensitivity analyses, with the exception of the role-emotional (RE) domain of SF-36, which did not retain significance after Bonferroni correction. Molecular analyses revealed elevated expression of lncRNA AP005432.1 and increased levels of pro-inflammatory cytokines in patients with AS, both of which decreased following HQC treatment. In vitro experiments showed that PBMCs from patients with AS promoted FLS proliferation, upregulated lncRNA AP005432.1 expression, activated the PI3K/AKT signaling pathway, and enhanced the secretion of pro-inflammatory cytokines. These effects were reversed by HQC-containing serum or lncRNA AP005432.1 knockdown. Activation of the PI3K/AKT pathway attenuated the inhibitory effects of lncRNA AP005432.1 knockdown, whereas combined HQC treatment and lncRNA AP005432.1 knockdown enhances the inhibition of the activator-induced inflammatory responses. Conclusion HQC exposure is robustly associated with improved SPP and reduced inflammatory activity in AS after adjustment for multiple confounders. In vitro findings suggest that HQC may exert anti-inflammatory effects, at least in part, by downregulating lncRNA AP005432.1 and inhibiting activation of the PI3K/AKT signaling pathway. These results identify lncRNA AP005432.1 as a potential therapeutic target in AS and provide mechanistic support for further investigation of HQC.

This study aimed to evaluate the effect of Huangqin Qingre Chubi capsule (HQC) on self-perception of patients (SPP) with gouty arthritis (GA) and explore its potential action path. Using a nested case-control design, 150 eligible GA patients were matched into neutrophil to lymphocyte ratio (NLR) improved group and NLR unimproved group based on the presence or absence of NLR improvement. Stratified analysis, association rule, binary logistics regression model and mediating effect analysis were used to evaluate the protective effect of HQC on SPP. At baseline, patients in the NLR improved group demonstrated significantly higher scores in the SPP subscales of physical functioning (PF), bodily pain (BP), general health, vitality (VT), role emotional (RE), and health transition compared to those in the NLR unimproved group (P < .001). And they exhibited significantly lower scores on the Visual Analog Scale (VAS), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) (P < .01). HQC significantly improved SPP (including PF, role physical, BP, VT, RE, mental health, VAS, SAS, and SDS) in GA patients (P < .05). Stratified analyses and binary logistics regression showed that HQC had a significant protective effect on the SPP. Association rules showed that there was a co-occurrence pattern between HQC and improvement of SPP. Mediation analysis showed that NLR showed a complete mediating effect in the path of HQC improving PF (P < .001), SDS (P < .001), Syndrome of Dampness-Heat Quantitative Score (SDH) (P < .001) and Syndrome of Blood Stasis Quantitative Score (SBS) (P < .001). HQC is related to the improvement of SPP, inflammatory biomarkers and traditional Chinese medicine syndromes in GA patients, and it plays a protective effect on SPP through NLR.

ETHNOPHARMACOLOGICAL RELEVANCE:The Jianpi Qingre Tongluo method-Huangqin Qingre Chubi capsule (HQC) is a featured herbal drug that was created based on traditional Chinese medicine theory. HQC is approved as a clinical evidence-based prescription in China and has been used to treat gouty arthritis (GA) for many years. However, interdisciplinary and diversified research on HQC against GA inflammation is still lacking. AIM OF THE STUDY:This study aims to integrate real-world clinical analysis, bioinformatics, virtual screening, and in vitro and in vivo experiments to elucidate the potential mechanism of HQC in improving GA inflammation. MATERIALS AND METHODS:A retrospective analysis was conducted of laboratory metrics and self-perception of patients (SPP) scale of 1226 patients with GA based on real-world. The association rule algorithm was used to calculate the associations between HQC and laboratory metrics and SPP. Bioinformatics analyses were applied to predict key targets and key signaling pathways of HQC against GA. High-throughput virtual screening was adopted to screen the core active ingredients of HQC. GA rat model was constructed to evaluate the effects of HQC on inflammation in GA rats by joint observations, ELISA, and immunohistochemical staining (IHC). The effects of HQC on fibroblast-like synoviocytes (FLSs) of GA was evaluated using CCK8 assay, ELISA, WB, and immunofluorescence (IF). RESULTS:Significant improvements in inflammatory metrics and SPP were observed in patients with GA treated with HQC; these improvements were strongly associated with HQC. The bioinformatics analyses revealed that the key targets of HQC against GA inflammation were the NFKB1, TLR4, IL1B, IL10, CXCL2, CXCL8, PTGS2, NFE2L2, CYP19A1, and PPARA, while NF-κB signaling pathway was the key signaling pathway. Two core active molecules were identified by high-throughput virtual screening, i.e., 2-monoolein and 5,7,2,5-tetrahydroxy-8,6-dimethoxyflavone. HQC significantly improved the joint conditions of GA rats and down-regulated the levels of a series of pro-inflammatory markers. IHC showed that HQC was able to down-regulate TLR4/MyD88/NF-κB signaling pathway in the synovium. The cellular experiments indicated that HQC drug-containing serum significantly lowered the IL-1β, IL-6, TNF-α, and NLRP3 levels and elevated the IL-10 level. WB and IF demonstrated that HQC inhibited TLR4/MyD88/NF-κB signaling pathway expression. CONCLUSION:This study proved that HQC treated GA by attenuating joint and systemic inflammatory responses, primarily by inhibiting the TLR4/MyD88/NF-κB signaling pathway. This study was conducted solely on a single batch of HQC. Given the natural variability of herbs, the generalizability of these specific findings to all batches of HQC requires further confirmation.

Objective: This study evaluates whether Huangqin Qingre Chubi Capsule (HQC), a traditional Chinese medicine (TCM) compound, is associated with the risk of re-admission in patients with ankylosing spondylitis (AS). Methods: In this study, we retrospectively collected the clinical data of 1,296 AS patients. Patients were allocated into HQC and nonHQC groups. Baseline data between the two groups were matched with propensity score matching (PSM). Influencing factors for the risk of re-admission in AS patients were analyzed with the Cox proportional hazards model. The effect of HQC intervention duration on the risk of re-admission was assessed with Kaplan-Meier survival curves. The random walk model and association rule analysis were utilized to determine the correlation between HQC and improvements in immunoinflammatory markers. Results: The re-admission rate was significantly lower in the HQC group than in the non-HQC group (P < 0.01). The risk of readmission was significantly lower in patients aged > 40 years (P < 0.01) than in patients aged < 40 years and also markedly lower in HQC users than in non-HQC users (P < 0.01), suggesting that age and the use of HQC were key factors influencing the risk of readmission. Longer HQC intervention duration was associated with better improvements in ESR, CRP, and C4, and HQC was closely correlated with improvements in ESR, CRP, IgA, and C4. Conclusion: HQC treatment can reduce the risk of re-admission in AS patients, which may be associated with improvements in ESR, CRP, IgA, and C4. The risk decreases with prolonged HQC treatment.

ETHNOPHARMACOLOGICAL RELEVANCE:Jianpi Qingre Chubi prescription primarily consists of a compound formula, also known as Huangqin Qingre Chubi Capsules (HQC), which strengthens the spleen and resolves dampness, clear heat, and collaterals. Long-term clinical use has shown that HQC improves joint swelling and pain in patients with osteoarthritis. Mechanistically, we demonstrated that HQC inhibits inflammatory responses, extracellular matrix degradation, and delays chondrocyte senescence. AIM:To determine the bioactivity and mechanism of action of Jianpi Qingre Tongluo prescription (HQC) on osteoarthritis (OA). MATERIALS AND METHODS:First, the chondroprotective effects of HQC were assessed using histopathology, immunohistochemical staining and protein blotting in an OA rat model. Additionally, we identified key targets for crucial targets of HQC in OA using the Network Pharmacology and Gene Expression Omnibus (GEO) dataset (GSE98918 and GSE152805). In vitro conditions, IL-1β-treated chondrocytes served to study the impact of HQC on OA development and the senescence-associated secretory phenotype (SASP). This was evaluated using a series of approaches, such as flow cytometry assays, and immunofluorescence staining, and then verified by rescue experiments. RESULTS:Therapy with HQC attenuated the severity of osteoarthritis (demonstrated by histopathology, OARSI grading scores, and Mankin scores) and SASP factors (as indicated by IL-1β, IL-6, IL-4, IL-37, MMP13, ADAMTS5, COL2A1, and ACAN levels, and apoptotic cell death). HQC might treat osteoarthritis via four important targets (STAG1, TP53, P21, and P16), with the p53 signalling pathway representing one of the main pathways. The HQC acts primarily on chondrocyte clusters. In vitro experiments indicated that STAG1 overexpression accelerates chondrocyte apoptosis, promotes SASP factor expression and extracellular matrix (ECM) degradation, and facilitates OA progression. HQC-containing serum suppressed the expression of the STAG1/TP53/P21 pathway, regulated SASP factors, and restored ECM balance. CONCLUSION:Jianpi Qingre Tongluo prescription modulated SASP factors by regulating the STAG1/TP53/P21 signal transduction axis and decelerating cartilage senescence and degradation in patients with OA. Jianpi Qingre Tongluo may be an effective drug candidate.

BACKGROUND:People with osteoarthritis place a huge burden on society. Early diagnosis is essential to prevent disease progression and to select the best treatment strategy more effectively. In this study, the aim was to examine the diagnostic features and clinical value of peripheral blood biomarkers for osteoarthritis. OBJECTIVE:The goal of this project was to investigate the diagnostic features of peripheral blood and immune cell infiltration in osteoarthritis (OA). METHODS:Two eligible datasets (GSE63359 and GSE48556) were obtained from the GEO database to discern differentially expressed genes (DEGs). The machine learning strategy was employed to filtrate diagnostic biomarkers for OA. Additional verification was implemented by collecting clinical samples of OA. The CIBERSORT website estimated relative subsets of RNA transcripts to evaluate the immune-inflammatory states of OA. The link between specific DEGs and clinical immune-inflammatory markers was found by correlation analysis. RESULTS:Overall, 67 robust DEGs were identified. The nuclear receptor subfamily 2 group C member 2 (NR2C2), transcription factor 4 (TCF4), stromal antigen 1 (STAG1), and interleukin 18 receptor accessory protein (IL18RAP) were identified as effective diagnostic markers of OA in peripheral blood. All four diagnostic markers showed significant increases in expression in OA. Analysis of immune cell infiltration revealed that macrophages are involved in the occurrence of OA. Candidate diagnostic markers were correlated with clinical immune-inflammatory indicators of OA patients. CONCLUSION:We highlight that DEGs associated with immune inflammation (NR2C2, TCF4, STAG1, and IL18RAP) may be potential biomarkers for peripheral blood in OA, which are also associated with clinical immune-inflammatory indicators.

Objective:To identify inflamm-aging related biomarkers in osteoarthritis (OA).Methods:Microarray gene profiles of young and aging OA patients were obtained from the Gene Expression Omnibus (GEO) database and aging-related genes (ARGs) were obtained from the Human Aging Genome Resource (HAGR) database. The differentially expressed genes of young OA and older OA patients were screened and then intersected with ARGs to obtain the aging-related genes of OA. Enrichment analysis was performed to reveal the potential mechanisms of aging-related markers in OA. Three machine learning methods were used to identify core senescence markers of OA and the receiver operating characteristic (ROC) curve was used to assess their diagnostic performance. Peripheral blood mononuclear cells were collected from clinical OA patients to verify the expression of senescence-associated secretory phenotype (SASP) factors and senescence markers.Results:A total of 45 senescence-related markers were obtained, which were mainly involved in the regulation of cellular senescence, the cell cycle, inflammatory response, etc. Through the screening with the three machine learning methods, 5 core senescence biomarkers, including FOXO3, MCL1, SIRT3, STAG1, and S100A13, were obtained. A total of 20 cases of normal controls and 40 cases of OA patients, including 20 cases in the young patient group and 20 in the elderly patient group, were enrolled. Compared with those of the young patient group, C-reactive protein (CRP), interleukin (IL)-6, and IL-1β levels increased and IL-4 levels decreased in the elderly OA patient group (P<0.01); FOXO3, MCL1, and SIRT3 mRNA expression decreased and STAG1 and S100A13 mRNA expression increased (P<0.01). Pearson correlation analysis demonstrated that the selected markers were associated with some indicators, including erythrocyte sedimentation rate (ESR), IL-1β, IL-4, CRP, and IL-6. The area under the ROC curve of the 5 core aging genes was always greater than 0.8 and the C-index of the calibration curve in the nomogram prediction model was 0.755, which suggested the good calibration ability of the model.Conclusion:FOXO3, MCL1, SIRT3, STAG1, and S100A13 may serve as novel diagnostic biomolecular markers and potential therapeutic targets for OA inflamm-aging.

Ethnopharmacological relevance: Huangqin Qingre Chubi Capsule (HQC) is a Chinese medicinal compound used for the treatment of damp -heat pattern rheumatism, guided by the traditional Chinese medicine syndrome differentiation practice. HQC has been used in the clinical treatment of rheumatic diseases for more than 20 years with remarkable efficacy. HQC has been experimentally shown to exert anti -arthritic effects via the Wnt signaling pathway. Aim of the study: This study used clinical data mining, network analysis, and in vitro and in vivo tests to investigate the anti -arthritic and possible anti-inflammatory mechanism of HQC. Specifically, emphasis was placed on the function of the hsa_circ_0091,685/EIF4A3/IL-17 axis in the anti-inflammatory process. Materials and methods: A random walk model was used to evaluate the effects of HQC on clinical immune inflammatory marker function in patients with RA. Network analysis was used to predict the potential target genes and pathways of HQC. Hematoxylin & eosin, safranin O -fast green and toluidine blue staining, immunohistochemistry, and transmission electron microscopy were performed to evaluate the anti -arthritic effects of HQC in rat models. Cell Counting Kit -8 assay, quantitative real-time polymerase chain reaction, western blotting, enzyme -linked immunosorbent assay, and RNA pull -down were used to study the anti -proliferation and antiinflammatory mechanisms of HQC. Results: Patients with RA who underwent HQC treatment showed a significant reduction in inflammatory response levels, according to retrospective clinical study. Network analysis revealed that HQC potentially targeted genes and pathways related to inflammation, especially IL -6, IL -17, TNF-alpha, IL -23, and IL -17 signaling pathway. Animal experiments showed that HQC inhibits inflammation through the IL -17 signaling pathway in rat models. Cellular experiments showed that HQC-containing serum inhibited the inflammatory response in patients with RA-FLS or RA by blocking hsa_circ_0091,685 and EIF4A3 expression. Conclusion: In RA patients, HQC reduces the inflammatory response. The antiproliferative and anti-inflammatory qualities of HQC are responsible for its therapeutic impact. The suppression of the hsa_circ_0091,685/EIF4A3/IL17 axis was linked to these favorable outcomes.

ObjectiveThe aim of this study was to investigate the relationship between Traditional Chinese medicine (TCM) and pain reduction, hospital readmission, and joint replacement in patients with osteoarthritis (OA). Chinese herbal medicine (CHM) prescription patterns were further analyzed to confirm the association with prognosis and quality of life in OA patients.MethodsWe retrospectively followed 3,850 hospitalized patients with osteoarthritis between January 2018 and December 2022 using the hospital's HIS system. Propensity score matching (PSM) was used for data matching. Cox's proportional risk model was used to assess the impact of various factors on the outcomes of patients with OA, including pain worsening, readmission, and joint replacement. The Kaplan-Meier survival curve was applied to determine the impact of TCM intervention time on patient outcomes. Data mining methods including association rules, cluster analysis, and random walks have been used to assess the efficacy of TCM.ResultsThe utilization rate of TCM in OA patients was 67.01% (2,511/3,747). After PSM matching, 1,228 TCM non-user patients and 1,228 TCM user patients were eventually included. The outcomes of pain worsening, re-admission rate, and joint replacement rate of the TCM non-user group were observably higher than those of the TCM user group with OA (p < 0.05). Based on the Cox proportional risk model, TCM is an independent protective factor. Compared with non-TCM users, TCM users had 58.4% lower rates of pain, 51.1% lower rates of re-admission, and 42% lower rates of joint replacement. In addition, patients in the high-exposure subgroup (TCM＞24 months) had a markedly lower risk of outcome events than those in the low-exposure subgroup (TCM ≤24 months). Data mining methods have shown that TCM therapy can significantly improve immune-inflammatory indices, VAS scores, and SF-36 scale scores in OA patients.Conclusions TCM acts as a protective factor to improve the prognosis of patients with OA, and the benefits of long-term use of herbal medicines are even greater.

This study aims to investigate the mechanism of Huangqin Qingre Chubi Capsules(HQC)in delaying chondrocyte senescence of osteoarthritic(OA)rats by regulating the p53/p21 signaling pathway.Rheumatic fever paralysis models of OA rats were induced based on monosodiun iodoacetate(MIA)combined with external rheumatic fever environmental stimuli and divided into normal(Con)group,OA model(MIA)group,OA model+rheumatic fever stimulation model(MIA-M)group,MIA-M+HQC low-dose(MIA-M+HQC-L)group,medium-dose(MIA-M+HQC-M)group,and high-dose(MIA-M+HQC-H)group,and MIA-M+glucosamine(MIA-M+GS)group.The models were successfully prepared and administered by gavage for 30 d.The pathological changes of cartilage were observed by hematoxylin-eosin(HE)and Senna O solid green(SO)staining.The expression of interleukin(IL)-1β and IL-6 was detected by enzyme-linked immunosorbent assay(ELISA).Flow cytometry(FCM)was used to detect apoptosis and cell cycle.The mRNA expression of MMP13,ADAMTS-5,COLⅡ,and TGF-β was detected by RT-qPCR.The protein expression of p53/p21,p16,Bax,and Bcl-2 was detected by Western blot.The articular cartilage surface of rats in the Con group was smooth,and the tide line was smooth.The cartilage layer of MIA and MIA-M groups was obviously damaged,and the cartilage matrix was reduced.The above conditions were more severe in the MIA-M group.The cartilage surface of the HQC high-dose group and MIA-M+GS group was basically intact with clear delamination.Compared with the MIA-M+HQC-H group,Mankin's score was higher in the HQC low-dose and medium-dose groups,and the change was not obvious in the MIA-M+GS group.Compared with the Con group,the proportion of chondrocytes G1 was elevated in the MIA and MIA-M groups,and the proportion of the S phase and G2 phase was significantly decreased.In addition,the apoptosis rate was increased.Compared with MIA-M,HQC groups inhibited apoptosis and promoted cell proliferation in a concentration-dependent manner.Compared with the MIA-M+HQC-H group,the effect was more significant in the HQC high-dose group than in the HQC medium-low dose,while it was not significant in the MIA-M+GS group.Compared with the Con group,IL-1β and IL-6 were elevated in the MIA and MIA-M groups,and mRNA levels of MMP13 and ADAMTS-5 were elevated.p53,p21,p16,and Bax protein were elevated,and mRNA levels of COLⅡ and TGF-β were decreased.Compared with the MIA-M group,IL-1β and IL-6 decreased after drug interventions of HQC and GS,and mRNA levels of MMP13 and ADAMTS-5,as well as protein levels of p53,p21,Bax,and p16 decreased.In addition,Bcl-2 increased.The improvement of these indexes was significantly better in the MIA-M+HQC-H group than in the HQC low-dose and medium-dose groups,and the difference with the MIA-M+GS group was not significant.HQC delayed MIA-induced chondrocyte senescence in OA rats,inhibited inflammatory response and extracellular matrix(ECM)degradation,and its mechanism may be related to the inhibition of the p53/p21 pathway.

Objective:To screen for long non-coding RNA (lncRNA) molecular markers characteristic of osteoarthritis (OA) by utilizing the Gene Expression Omnibus (GEO) database combined with machine learning.Methods:The samples of 185 OA patients and 76 healthy individuals as normal controls were included in the study. GEO datasets were screened for differentially expressed lncRNAs. Three algorithms, the least absolute shrinkage and selection operator (LASSO), support vector machine recursive feature elimination (SVM-RFE), and random forest (RF), were used to screen for candidate lncRNA models and receiver operating characteristic (ROC) curves were plotted to evaluate the models. We collected the peripheral blood samples of 30 clinical OA patients and 15 health controls and measured the immunoinflammatory indicators. RT-PCR was performed for quantitative analysis of the expression of lncRNA molecular markers in peripheral blood mononuclear cells (PBMC). Pearson analysis was performed to examine the correlation between lncRNA and indicators for inflammation of the immune system.Results:A total of 14 key markers were identified with LASSO, 6 genes were identified with SVM-RFE, and 24 genes were identified with RF. Venn diagram was used to screen for overlapping genes identified with the three algorithms, showing HOTAIR, H19, MIR155 HG, and NKILA to be the overlapping genes. The ROC curves showed that these four lncRNAs all had an area under the curve ( AUC) greater than 0.7. The RT-PCR findings revealed relatively elevated expression of HOTAIR, H19, and MIR155HG and decreased expression of NKILA in the PBMC of OA patients compared with those of the normal group ( P<0.01). The results were consistent with the bioinformatics predictions. Pearson analysis showed that the candidate lncRNAs were correlated with clinical indicators for inflammation.Conclusion:HOTAIR, H19, MIR155 HG, and NKILA can be used as molecular markers for the clinical diagnosis of OA and are correlate with clinical indicators of inflammation of the immune system.

Previous studies have shown that autophagic pathogenesis of rheumatoid arthritis (RA) is regulated by circular RNAs (circRNAs), which accelerate bone damage by participating in the immune inflammatory response. Therefore, exploring the mechanisms underlying circRNA regulation of autophagy is essential for maintaining homeostasis of the skeletal microenvironment in RA and may improve our understanding of the specific pathways involved in the development of therapeutics. In this review, we discuss autophagic imbalance in RA and the regulatory mechanisms of circRNAs. We also explore possible targets for circRNA regulation of autophagy in RA, which may provide us with improved knowledge regarding the pathogenesis of RA.

目的:分析新风胶囊(XFC)"异病同治"类风湿关节炎(RA)和骨关节炎(OA)的分子机制.方法:TCMSP数据库筛选XFC的活性成分及靶点,疾病数据库中筛选RA和OA的靶点,构建药物-成分-靶点网络.构建交集靶点的蛋白互作网络,进行功能富集分析和分子对接.绘制XFC治疗RA和OA信号通路.结果:共鉴定103种化合物和217个靶点,槲皮素、蜈蚣素、山柰酚、谷甾醇α1、芒柄花黄素、雷公藤甲素、豆甾醇、山海棠二萜内酯A等11个化合物与≥30个靶基因相关联,其中9个靶基因(STAT3、MAPK14、NR3C1、JUN、FOS、MYC、TNF、RELA和MAPK1)是网络中的核心靶基因.富集分析表明IL-17、TNF、Th17、Toll和NF-κB信号通路可能是关键信号通路.分子对接表明山海棠二萜内酯A、槲皮素、雷公藤甲素、谷甾醇α1、蜈蚣素与NR3C1、FOS、STAT3、MAPK1和TNF靶点具有良好的结合活性.结论:XFC"异病同治"RA与OA的机制与抗炎、免疫调节、减少骨破坏等相关,具有多系统、多成分、多靶点的作用.

Clinical practice has proved that Xinfeng capsule (XFC) can effectively cure osteoarthritis (OA). In our study, we investigated the molecular mechanism and role of XFC in the treatment of OA using network pharmacology and cellular experiments. hsa_circ_0032131 was overexpressed in OA peripheral blood mononuclear cells (PBMCs). Both PBMCs and chondrocytes are cellular members of the inflammatory microenvironment in OA. To investigate the function of hsa_circ_0032131 in PBMCs stimulated chondrocytes. A series of functional experiments revealed the relationship between hsa_circ_0032131 and the miR-502-5p/TRAF2 axis. To further determine whether XFC might treat OA through the interaction of circ_0032131 with the miR-502-5p/TRAF2 axis. CKK-8 assay and flow cytometry were conducted to detect the proliferation and apoptosis process of XFC-treated cells. Multiple experimental methods were utilized to detect the expression levels of inflammatory factors, extracellular matrix, and so on. The results demonstrated that the expression of hsa_circ_0032131 was obviously elevated in PBMCs of OA patients and correlated with clinical immuno-inflammatory factors and ECM indexes. Network pharmacology verified that the chief active ingredients of XFC exerted their roles mainly in the regulation of inflammation (IL1A, IL1B, IL4), extracellular matrix metabolism (MMP13, COL2A1), and tumour necrosis factor (TNF, TRAF2). In vitro experiments revealed that knockdown of circ_0032131 in PBMCs-stimulated chondrocytes inhibited apoptosis, inflammation and ECM degradation. Circ_0032131 was verified as a sponge of miR-502-5p by targeting, and TRAF2 was a direct target of miR-502-5p. In addition, rescue experiments verified that XFC blocked the effects of hsa_circ_0032131 overexpression on extracellular matrix, inflammation and cell viability. XFC has a favorable anti-inflammatory effect on OA, and its molecular mechanism was preliminarily elucidated.

目的:整理归纳针灸治疗腹型肥胖的方法、手法、穴位并分析临床治疗的规律性和仍存在的不足,为临床发展提供新的思路.方法:在中国知网中检索2016年至今关键词为针灸、腹型肥胖、中心性肥胖的文献并进行总结.结果:针灸在治疗腹型肥胖时,方法具有多样性但以电针居多;手法以提插捻转、平补平泻为主,进针深度、留针时间会影响最终疗效;选穴时以脾胃经为主,天枢穴为核心.结论:在治疗腹型肥胖方面,中医针灸疗法相比于西医运动、节食、手术等疗法有独特优势,针灸方法的多样性为医者提供了多种治疗途径,治疗的针刺手法和取穴也存在一定的规律可寻,为临床治疗腹型肥胖构建了框架.但目前还存在腹型肥胖疾病的病因、作用机制不明确,临床治疗尚未形成统一处方,辨证分型体系研究不够透彻,临床实验未规范要求等不足之处,有待进一步的深入研究.

Abstract Objective We intended to explore the anti-inflammatory and chondroprotective effects of Xinfeng capsule (XFC) in osteoarthritis (OA), perhaps through the regulation of hsa_circ_0032131 and miR-502-5p/TRAF2 axis. Materials and methods In total, 30 patients with OA and healthy subjects were recruited. To detect markers of cartilage metabolism and inflammation, peripheral blood mononuclear cells (PBMCs) were taken out. Subsequently, network pharmacology was employed to forecast OA-related targets and pathways for XFC therapy. To investigate the function of upregulated hsa_circ_0032131 in model cells.A series of functional experiments revealed the relationship between hsa_circ_0032131 and miR-502-5p/TRAF2 axis. To further determine whether XFC potentially treats OA through the interaction between circ_0032131 and miR-502-5p/TRAF2 axis. CKK-8 assay and flow cytometry were performed to detect cell proliferation and apoptotic processes in XFC-treated cells. Some conventional experimental methods were used to detect the expression levels of inflammatory factors, extracellular matrix and others. In addition, rescue experiments verified that XFC blocked the effects of hsa_circ_0032131 overexpression on extracellular matrix, inflammation and cell viability. Results Clinical observations indicated that the expression of hsa_circ_0032131 in PBMCs of OA patients was significantly elevated, and there was a correlation with clinical immuno-inflammatory factors and inflammatory indicators. Network pharmacology verified that the chief active ingredients of XFC exerted their roles mainly in the regulation of inflammation (IL1A, IL1B, IL4), extracellular matrix metabolism (MMP13, COL2A1), and tumour necrosis factor (TNF, TRAF2). In vitro experiments revealed that knockdown of circ_0032131 inhibited apoptosis, inflammatory and ECM degradation in PBMCs-stimulated chondrocytes. Circ_0032131 was verified to be a sponge of miR-502-5p by targeting, and TRAF2 was a direct target of miR-502-5p. By regulating circ_0032131 and miR-502-5p/TRAF2 axis, XFC prevented PBMCs-stimulated chondrocytes from responding to inflammation and ECM degradation. Conclusion The XFC suppressed inflammatory response and extracellular matrix metabolism in OA by regulating circ_0032131 and miR-502-5p/TRAF2 axis.

脂溢性脱发在日常生活中较为常见,且病因复杂,其发病机制尚未明确.随着人们生活水平的不断提高,人们对自身外在形象的要求也越来越高.中医药治疗脂溢性脱发具有较好的临床疗效,复发率低,且不良反应较少.侧柏叶气清香,味苦涩、微辛,归肺、肝、脾经,具有凉血止血、化痰止咳和生发乌发之功效.本研究通过概述脂溢性脱发的病因病机、侧柏叶治疗脂溢性脱发的作用成份及治疗机理、临床治疗相关研究和治疗效果,以期为临床治疗脂溢性脱发提供新方向和新思路.

目的 评价中药复方新风胶囊是否与强直性脊柱炎(AS)患者的终点事件(再入院、关节外表现和手术治疗)有关.方法 回顾性收集2012年6月—2022年6月在安徽中医药大学第一附属医院风湿免疫科出院的1621例AS患者的临床数据.按是否服用新风胶囊将患者分为新风胶囊组及非新风胶囊组.采用倾向性评分匹配方法来匹配基线数据.以随机行走模型评价规范化西药联合新风胶囊对免疫炎症指标改善情况的影响.关联规则分析新风胶囊与AS临床免疫炎症指标改善的关联度.进行多变量(包括新风胶囊、性别、年龄、原发性高血压、糖尿病、高脂血症、骨质疏松症、肝功能不全和慢性乙型肝炎)COX分析,确定再入院、关节外表现和手术治疗的风险.结果 最终有1455例AS患者被纳入该研究.经过倾向性评分匹配,新风胶囊使用者的基线数据与非新风胶囊使用者的基线数据一致,每组203例.回顾性数据挖掘结果显示,新风胶囊可明显降低AS患者的临床免疫炎症指标;随机行走模型结果提示,规范化西药联合新风胶囊治疗与免疫炎症指标的改善长程关联;关联规则分析结果显示,新风胶囊与免疫炎症指标的改善呈强关联.与非新风胶囊使用者相比,新风胶囊使用者总终点事件的预后更优(χ2=11.678,HR=0.65,95％CI=0.500～0.810,P<0.01).高暴露组(HR=0.504,95％CI=0.357～0.711)和中暴露组(HR=0.576,95％CI=0.380～0.873)的终点事件发生风险明显低于非暴露组.结论 中药复方新风胶囊与AS较低的终点事件(再入院、关节外表现及手术治疗)有关,可能是AS终点事件的保护因素,并且长期暴露于新风胶囊可能明显减少终点事件的发生.

Purpose: The therapeutic effects of Huangqin Qingre Chubi (HQC) in rheumatoid arthritis (RA) have been documented. However, there is a lack of real-world clinical evidence supporting its efficacy.Methods: Patients diagnosed with RA were recruited from the First Affiliated Hospital of the Anhui University of Chinese Medicine. Patient information was obtained from the hospital's database. Propensity score matching (PSM), Kaplan-Meier curve, and Cox proportional hazards model were used to control confounding factors and analyze the factors influencing readmission. Association rule analysis and random walk evaluation models were used to evaluate the correlations among HQC treatment, inflammation indicators, and self-perception of patients (SPP) scale.Results: After PSM, 3423 patients were enrolled, with 1142 in the HQC group and 2281 in the non-HQC group. The readmission risk of the HQC group was significantly lower than that of the non-HQC group. Combined univariate and multivariate analysis results revealed that risk factors for readmission were age >60 years, female sex, hypertension, chronic gastritis, and elevated levels of laboratory indices, including anticyclic citrullinated peptide and complement component 3 (C3) and C4. HQC, disease-modifying antirheumatic drugs, nonsteroidal anti-inflammatory drugs, and glucocorticoid therapy were protective factors for readmission. HQC treatment was closely associated with improvements in many factors, including erythrocyte sedimentation rate, C-reactive protein, C3, rheumatoid factor levels, visual analog scale, depression self-assessment scale, and patient-reported activity index scores with RA.Conclusion: HQC treatment can reduce the risk of readmission and significantly improve immune inflammatory indicators and SPP in patients with RA, with no risk of hepatorenal toxicity.

[目的]探讨明代温补学派痈疽诊疗思路与特色.[方法]从中医文献整理、研究的角度,对明代温补学派代表医家汪机、薛己、孙一奎的著作《外科理例》《外科枢要》《赤水玄珠》中以温补治疗痈疽的论述、医案、具体药方、针刺手法进行系统分析,归纳和总结其痈疽论治思路和特色.[结果]三位医家以温补论治,可使痈疽消之,不至寒凉太过耗损人体正气;扶正固本以助恢复,不致病情反复.汪机在内外兼治的基础上,强调经络辨证结合刺灸外治;薛己善辨痈疽脉象,以清补兼施为用药特色;孙一奎把握病程发展及病情转归,注重温补脾肾,用香药行气血以治痈疽.[结论]明代温补学派从温补角度论治痈疽,不对痈疽单纯以"火毒"论治,不使寒凉之剂攻伐太过,以补益脾胃、扶正固本为祛邪外出之法.而今日医家多治以寒凉,故进一步挖掘温补学派治法,于临床启发良多.