ABSTRACT Background Although recent animal experiments have revealed that tea intake improves elevated serum uric acid (SUA) levels, a causal link between the consumption of different types of tea and SUA levels remains undetermined. Methods Bidirectional Mendelian randomization (MR) analysis based on genome‐wide association studies was used to assess the causal relationship between consumption of different types of tea and the risk of elevated SUA levels in European and Asian populations. Results Forward MR analysis showed that tea intake was significantly associated with lower SUA levels ( p = 0.0013). The estimated effect value ( −0.0440) suggests that for every 1‐unit increase in tea intake, there is a 0.044‐unit decrease in SUA levels. However, there is no reverse causality between SUA and tea intake ( p = 0.2824). No causal relationship was found between the consumption of different types of tea and risk of elevated SUA levels ( p > 0.05). Conclusion Although this bidirectional MR study provided evidence of a causal relationship between tea intake and SUA levels, however, due to limitations associated with the sample size and strength of instrumental variables, a definite conclusion was not possible.

Gout and hyperuricemia represent significant global health burdens, characterized by painful inflammatory arthritis and systemic metabolic dysfunction, respectively. Current pharmacological management faces substantial limitations, including poor bioavailability, systemic toxicity, narrow therapeutic indices, immunogenicity, and suboptimal patient adherence due to frequent dosing and adverse effects. These challenges underscore the critical need for innovative therapeutic strategies. Advanced drug delivery systems (DDSs) have emerged as transformative solutions to overcome these hurdles. This comprehensive review critically analyzes recent advances in DDSs tailored to the management of gout and hyperuricemia. We first elucidate the intricate pathophysiological mechanisms linking hyperuricemia, monosodium urate (MSU) crystal deposition, NLRP3 inflammasome activation, and chronic inflammation. We then systematically explore cutting-edge DDS platforms, including lipid-based, polymer-based, and other systems. These engineered drug delivery systems significantly enhance therapeutic outcomes in gout and hyperuricemia by improving drug solubility, enabling targeted delivery, providing sustained release, facilitating synergistic drug co-delivery, and responding to pathological microenvironments, although preclinical evidence is limited and clinical evidence supporting their efficacy and safety remains sparse. Finally, we highlight translational challenges and future directions while emphasizing the considerable promise of integrating AI, biomaterial science, and personalized medicine to advance patient-centric DDS. Although progress has been made, sustained interdisciplinary collaboration and rigorous clinical validation remain critical to translate these innovations into tangible improvements in long-term disease management and quality of life for patients with gout and hyperuricemia.

Objective: To explore the risk factors for uric acid-lowering therapy-resistant gout (UALT-RG) and its relationships with the estimated glomerular filtration rate (eGFR), body roundness index (BRI), and visceral adiposity index (VAI) via 2007-2018 National Health and Nutrition Examination Survey (NHANES) data. Methods: We calculated the BRI using waist circumference and standing height; the VAI using triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), and body mass index (BMI); and the eGFR from serum creatinine levels. We also collected gout data. We explored the relationships of the eGFR, BRI, and VAI with UALT-RG risk via univariable and multivariable weighted logistic regression, trend analysis, and restricted cubic splines. Results: Among the 1,811 patients with gout, similar to 9.08% had UALT-RG; these patients were more likely to have obesity, comorbid diabetes (36% [27-47%] vs. 25% [22-28%]) or impaired kidney function (eGFR < 60 mL/min/1.73 m(2), 34.5% [27-43%] vs. 22.5% [20-26%]); be former smokers; and take colchicine (10% [5.6-19%] vs. 4.3% [2.8-6.7%]). Logistic regression and trend analysis suggested that an elevated BRI and decreased eGFR were independent risk factors and potential screening indicators for UALT-RG. Restricted cubic spline analysis revealed a negative linear trend between the eGFR and UALT-RG risk (p-overall < 0.0001) and a significant positive correlation between the BRI and UALT-RG risk (p-overall < 0.0001). Conclusion: An increased BRI and decreased eGFR may be independent risk factors and assessment indicators for UALT-RG in U.S. adults. It is necessary to monitor serum urate levels more closely and conduct early multidisciplinary comanagement when gout is comorbid with visceral obesity and chronic kidney disease stages 3-5.

Background: Vitamin C, a common antioxidant, may be useful for treating hyperuricemia and gout. The aim of this study was to investigate the risk association between dietary vitamin C intake and hyperuricemia/gout and to test for causality using the bi-directional Mendelian randomisation method. Methods: Cross sectional studies were selected from the National Health and Nutrition Examination Survey from 2007 to 2018 to assess the association between dietary vitamin C intake and the risk of hyperuricemia/gout, according to multivariate logistic regression modelling. Bi directional Mendelian randomisation studies were conducted using genetic data from large scale genome wide association surveys of supplemental vitamin C, pharmacological vitamin C, and ascorbic acid intake and hyperuricemia/gout; these aimed to infer causal relationships between vitamin C and hyperuricemia/gout. Inverse variance weighting was used as the primary method of Mendelian randomisation analysis. A series of sensitivity analyses were used to assess multiplicity. Results: The cross-sectional study included 17.52% and 82.48% patients with and without hyperuricemia, respectively, as well as 2.67% and 97.33% patients with and without gout, respectively. In the model correcting for all covariates, the association between vitamin C intake and the risk of hyperuricemia/gout was stable, and the risk of hyperuricemia was generally lower in patients who consumed >111.75 mg vitamin C than in other patients when comparing three models with different moderators. Restricted cubic spline scores indicated that vitamin C intake recommendations of 75 to 525 mg and 75 to 225 mg were effective for targeting hyperuricemia and gout, respectively. In inverse variance weighting in the Mendelian randomisation analysis, the amount of vitamin C absorbed was negatively associated with hyperuricemia (OR = 0.985, 95% CI = 0.973 to 0.997, p = 0.015), and supplemental vitamin C was negatively associated with gout (OR = 0.857, 95% CI = 0.797 to 0.921, p < 0.001); sensitivity analysis yielded consistent results. Reverse Mendelian randomisation analysis showed that vitamin C had no reverse causal relationship with hyperuricemia and gout. Conclusion: We hypothesise that a dietary vitamin C intake of 75 to 525 mg or 75 to 225 mg may reduce the risk of hyperuricemia and gout, respectively. Further research with larger samples is required to confirm this.### Competing Interest StatementThe authors have declared no competing interest.### Funding StatementThis work was supported by the National Natural Science Foundation of China (81960863 and 82160901), Construction Project of Yunnan Provincial Fund for Medical Research Center (202102AA310006), Construction Project of National Traditional Chinese Medicine Clinical Research Base (2018 No. 131), Construction Project for the Focal Branch of National Traditional Chinese Medicine (2023 No. 85), The Expert Workstation of Zhangxuan in Yunnan Province (202305AF150175), Funding of Yunnan Applied Basic Research Projects-Union Applied Basic Research Projects-Union Foundation (2019FF002[-082], 2019FF002[-031], 202101AZ070001-072 and 202101AZ070001-074), and Yunnan Provincial Traditional Chinese Medicine Discipline Reserve Talent Training Project (2021 No. 01).### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The study used (or will use) ONLY openly available human data that were originally located at: https://www.cdc.gov/nchs/nhanes/index.htm and https://gwas.mrcieu.ac.uk/.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesAll data produced in the present study are available upon reasonable request to the authors. All data produced in the present work are contained in the manuscript. All data produced are available online at.

Glucocorticoids (GC) are crucial in the treatment of rheumatoid arthritis (RA), but discontinuing GC effectively in RA patients poses a significant challenge for rheumatologists. In this two-stage, single-center, non-randomized controlled trial, we investigated the benefits of combining Chinese traditional herbal treatment with csDMARDs to aid GC discontinuation in terms of GC tapering, disease control, and safety. A total of 231 participants were enrolled, of which 150 eligible subjects were included in the first phase and allocated to three groups (control group, treatment group 1, and treatment group 2) based on their willingness to take traditional Chinese medicine and syndrome differentiation, in a 1:1:1 ratio. All groups received basic treatment consisting of methotrexate tablets (10 mg, qw), leflunomide (10 mg, qd), and stratified GC bridging therapy and tapering regimen (The intervention regimen was developed based on rigorous adherence to available evidence). Treatment group 1 received basic treatment combined with Juanbi Granule, while treatment group 2 received basic treatment combined with Yupingfeng Guizhi Decoction Granule. Efficacy was evaluated after a 12-week follow-up, with slightly adjustments to the treatment group based on efficacy and change of syndrome, followed by continued observation until 24 weeks to complete the study. The efficacy evaluation and data analysis were conducted in a blinded manner, including group label concealment, data cleaning, confounder and control regimen analysis, and outcome analysis. This project has received ethical approval from the Ethics Committee of Yunnan Provincial Hospital of Traditional Chinese Medicine (YLZ [2022] Ethical Review No. (006)-01) and has been registered with the China Clinical Trials Registry (Registration number: ChiCTR2300067676, Registered 17 January 2023, https://www.chictr.org.cn/showproj.html?proj=184908). This trial was the first to evaluate the clinical efficacy of combining Chinese herbal medicines with standard Western medicines to facilitate the discontinuation of glucocorticoid (GC) therapy in patients with rheumatoid arthritis (RA).

OBJECTIVE:This study aimed to explore the link between dietary vitamin C intake and hyperuricemia/gout, utilizing Mendelian randomization to assess causality. METHODS:We analyzed cross-sectional data from the National Health and Nutrition Examination Survey (2007-2018) to investigate the association. Mendelian randomization studies, using genetic data from genome-wide association surveys, were conducted to infer causality between vitamin C intake and hyperuricemia/gout. The weighted logistic regression analysis and the instrumental variable based on the inverse-variance weighting served as the primary analytical tool, with sensitivity analyses to ensure robustness. RESULTS:After adjusting for covariates, a stable association was observed between vitamin C intake and hyperuricemia/gout risk. Those consuming >111.75 mg of vitamin C generally had a lower risk. Vitamin C intake recommendations of 75-525 mg and 75-225 mg appeared effective for hyperuricemia and gout, respectively. Mendelian randomization analysis revealed a negative association between vitamin C intake and hyperuricemia (OR = 0.985, 95% CI = 0.973-0.997, p = .015) and gout (OR = 0.857, 95% CI = 0.797-0.921, p < .001). Reverse Mendelian randomization indicated no reverse causality. CONCLUSION:We hypothesize that a dietary vitamin C intake of 75-525 mg or 75-225 mg may reduce the risk of hyperuricemia and gout, respectively. Further research with larger samples is required to confirm this.

BACKGROUND:Orthosiphon stamineus Benth is a dietary supplement and traditional Chinese herb with widespread clinical applications, but a comprehensive understanding of its active compounds and polypharmacological mechanisms is lacking. This study aimed to systematically investigate the natural compounds and molecular mechanisms of O. stamineus via network pharmacology.METHODS:Information on compounds from O. stamineus was collected via literature retrieval, while physicochemical properties and drug-likeness were evaluated using SwissADME. Protein targets were screened using SwissTargetPrediction, while the compound-target networks were constructed and analyzed via Cytoscape with CytoHubba for seed compounds and core targets. Enrichment analysis and disease ontology analysis were then carried out, generating target-function and compound-target-disease networks to intuitively explore potential pharmacological mechanisms. Lastly, the relationship between active compounds and targets was confirmed via molecular docking and dynamics simulation.RESULTS:A total of 22 key active compounds and 65 targets were identified and the main polypharmacological mechanisms of O. stamineus were addressed. The molecular docking results suggested that nearly all core compounds and their targets possess good binding affinity. In addition, the separation of receptor and ligands was not observed in all dynamics simulation processes, whereas complexes of orthosiphol Z-AR and Y-AR performed best in simulations of molecular dynamics.CONCLUSION:This study successfully identified the polypharmacological mechanisms of the main compounds in O. stamineus, and predicted five seed compounds along with 10 core targets. Moreover, orthosiphol Z, orthosiphol Y, and their derivatives can be utilized as lead compounds for further research and development. The findings here provide improved guidance for subsequent experiments, and we identified potential active compounds for drug discovery or health promotion.

IMPORTANCE: Chronic kidney disease (CKD) presents a major public health problem in adults and significantly contributes to morbidity and mortality. Cardiovascular disease (CVD) is the most common comorbidity of CKD. Statin use is known to reduce the incidence of CVD while evidence of an effect on CKD all-cause mortality is limited.OBJECTIVE: To investigate the mortality risks associated between statin use and CKD in US adults.DESIGN, SETTING, AND PARTICIPANTS: This is a cross-sectional study with data from the 2005 to 2016 cycle of the National Health and Nutrition Examination Survey (NHANES), a population-based nationally representative sample of US adults. The target population consisted in adult patients with CKD if they were aged ³18 years at the time of participation in the main NHANES study. Exclusion criteria included those of the main NHANES study, inability to complete testing, or mission questionnaires. Of the 8036 participants in NHANES aged ³18 during the study years, 2102 were included in the analysis. Analysis was conducted from July 25, 2022, to September 5, 2022.EXPOSURES Statin use was determined through a pill bottle review during the in-home questionnaire, including atorvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin.MAIN OUTCOMES AND MEASURES: The a priori hypothesis that there is a negative association between statin use and CKD all-cause mortality in the studypopulation was tested. Analysis included Cox regression with adjustment for possible confounders. Interaction terms and subgroup analysis were conducted.RESULTS: A total of 2102 adult were included in the analysis, representing 11 million US population. Patients taking statins were significantly older (56.0 [0.7] years vs 68.9 [0.7] years vs 69.7 [1.4] years vs 67.6 [1.5] years vs 67.9 [1.2] years vs 71.0 [0.8] years), more frequently male (61.4% [ 95% CI, 58.3%-64.5%] vs 38.6% [95% CI, 35.5%-41.7%]) and had a higher BMI. The Hazard Rate (HRs) for atorvastatin (HR, 0.43 [95% CI, 0.24-0.79]) and simvastatin (HR, 0.55 [95% CI, 0.35-0.89]) had lower all-cause mortality risks than no use statin. These ratios were intensified by adjustment for covariates. There is a significant interaction between CVD and statin use (unadjusted model p-interaction = 0.03).CONCLUSIONS AND RELEVANCE: This study suggests that statin use is associated with the CKD all-cause mortality in US adults. This modifiable risk factor suggests a target for further research into reducing CKD all-cause mortality in US adults.Funding: Dr. Li was supported by grant 82074187 from the National Natural ScienceFoundation; Dr. Peng was supported by grant 82160901 from the National Natural ScienceFoundation and grant 2018 No. 131 from the construction Project of the National TraditionalChinese Medicine Clinical Research Base.Declaration of Interest: The authors declare no competing interests.Ethical Approval: The NHANES study has been continuously managed by the National Center for Health Statistics and Ethics Review Board since 1999. The Albert Einstein College of Medicine Institutional Review Board formally classified using deidentified data for secondary analysis as exempt. The NHANES study included written informed consent from all participants and using the existing data for this secondary analysis was not required for specific written consent. We drafted this report in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cross-sectional studies

Syndrome (Zheng in Mandarin Chinese) is the induction of disease attributes in the theory of traditional Chinese medicine (TCM). This is often used to explain why patients with the same disease show different symptoms. Cold and heat represent the two basic tendencies of a syndrome; therefore, the identification of cold and heat syndromes is key to the diagnosis and treatment of rheumatoid arthritis (RA) according to TCM. However, a traditional thinking model of cold and heat syndromes identifies a reliance on the clinical manifestations, which is inevitably affected by the subjectivity of doctors. It is important to identify objective biomarkers to improve accuracy in the identification of cold and heat syndromes of RA. Previous studies have identified differences in gene expression and function between cold and heat syndromes of RA, suggesting that different syndromes possess a unique biological basis.1,2 However, the biological basis is large and complex; therefor constructing a “disease– syndrome– biomaker” network using modern technology to preserve the characteristics of TCM and also improve the objectivity and applicability in syndrome identification is challenging DNA hydroxymethylation is an epigenetic marker that has attracted increasing attention recently. As a bridge between methylation and demethylation, DNA hydroxymethylation drives demethylation, indicating the reactivation of gene transcriptional expression.3 More importantly, DNA hydroxymethylation is sensitive to environmental stimuli, the state of DNA hydroxymethylation modification is able to change under different environmental stimuli, resulting in phenotypic differences.4 This regulatory mechanism is consistent with the concept of TCM, whereby “environmental differences can break the balance between cold and heat, causing differences in external clinical symptoms in patients with RA”, inferring that it is feasible to explore the epigenetic biomarkers of cold and heat syndromes of RA from DNA hydroxymethylation and gene transcription. The aim of our study was to identify epigenetic biomarkers of cold and heat syndromes of RA by combining DNA hydroxymethylation sequencing and transcriptome sequencing. Our study was approved through ethical review by the First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine (ethical batch number: the scientific research [2020] Ethical Review [005]02). The study was conducted as follows. Ten patients with RA cold syndrome and 10 with heat syndrome were recruited according to the Guideline for Diagnosis and Treatment of Rheumatoid Arthritis Based on TCM Syndromes.5 We also included 10 healthy participants. The general situation of these groups is shown in Table 1. Next, 10 mL peripheral venous blood was extracted from each participant to isolate peripheral blood mononuclear cells; DNA and RNA were further extracted. Hydroxymethylated DNA fragments were obtained through DNA hydroxymethylation immunoprecipitation (hMeDIP), and mRNA was obtained through enzyme digestion. The Illumina highthroughput sequencing platform was used to generate the library, in addition to hMeDIP sequencing (hMeDIPseq) and mRNA sequencing (mRNAseq). Bioinformatics analysis was used to compare the changes in DNA hydroxymethylation and transcriptional expression between cold and heat syndrome genes. Remarkably altered genes at DNA hydroxymethylation were used in Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment. Genes significantly altered at both the DNA hydroxymethylation and transcription expression levels were identified as epigenetic biomarkers of cold and heat syndromes of RA and the correlation was preliminarily analyzed. Results demonstrated that genomes with significant hydroxymethylation alteration tended to have a higher hydroxymethylation level (Figure S1A). Among 754 differential genes screened, 737 genes showed upregulation (logFC ≥ 1, P < 10−4), involved in 32 pathways including the Wnt signaling pathway, T helper type 17 cell differentiation pathway, and neuroactive ligandreceptor interaction (Figure S1B). The expression of 17 genes was downregulated (logFC ≤ −1, P < 10−4) and related to African trypanosomiasis, Malaria, and Axonal guidance pathways (Figure S1C). There were 125 genes with significant hydroxymethylated changes from patients with heat syndrome (Figure S1D). Among which, 64 genes indicated upregulated expression (logFC ≥ 1, P < 10−4) and enriched Arginine and proline metabolism (Figure S1E). The remaining 61 genes with

目的:调查和分析当前痛风发病情况和中医证候分布规律.方法:收集2019年1月至2022年1月云南省中医医院、南通良春中医医院等23家医院的1017例痛风患者,分析痛风患者基本情况、中医证候分布规律,中医证候在年龄、病情分期、血脂、血尿酸等方面的分布情况.结果:湿热蕴结证是痛风患者主要的中医证候,占70.21％.湿热蕴结证、寒湿痹阻证、痰瘀痹阻证均以急性期为主,分别占61.62％、54.65％、45.36％.脾虚湿阻证及肝肾阴虚证多见于间歇期及慢性期分别占46.81％和46.15％.不同证候年龄分布比较,差异有统计学意义(P<0.01);不同证候患者之间血尿酸水平比较,差异有统计学意义(P<0.05).结论:痛风发病年龄呈现年轻化趋势,中医证候分布与患者年龄、部分伴发疾病和血尿酸水平存在明显差异;痛风不同时期、证候分布也不相同.可为痛风辨证论治、规范治疗提供参考依据.

目的 探讨类风湿关节炎(RA)合并糖代谢异常的临床特点及危险因素.方法 对2017年1月-2022年1月于云南省中医医院风湿病科住院的1157例RA患者进行回顾性分析,分为RA组、RA合并空腹血糖受损(IFG)组与RA合并2型糖尿病(T2DM)组,比较3组患者的临床资料,包括人口学特征、空腹血糖(GLU)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、血尿酸(sUA)、红细胞沉降率(ESR)、C反应蛋白(CRP)、类风湿因子(RF)、抗环瓜氨酸肽(CCP)抗体检测结果.采用Logistic回归分析RA患者发生IFG和T2DM的危险因素.结果 RA合并IFG组年龄、病程、RF-IgM、ESR、CRP、TC、LDL-C、GLU均高于RA组,差异均有统计学意义(P<0.05).RA组年龄、病程、RF-IgG、CRP、UA、TC、TG、LDL-C、GLU水平以及高脂血症患者的比例明显低于RA合并T2DM组,差异均有统计学意义(P<0.05).Logistic多因素分析发现,ESR、CRP、LDL-C、GLU水平升高均是RA患者发生IFG的独立危险因素,长RA病程,高水平LDL-C和GLU均是RA患者发生T2DM的独立危险因素.结论 RA合并IFG和T2DM患者存在多种代谢指标异常,ESR、CRP、LDL-C水平升高导致RA患者发生IFG的可能性增加;长RA病程,高水平LDL-C均可导致RA患者发生T2DM的可能性增加.

目的 运用网络药理学技术研究白芍-甘草治疗强直性脊柱炎的可能作用机制.方法 通过检索TC-MSP数据库获取中药的化学成分信息和潜在靶点;疾病靶点由GeneCards、OMIM、TTD、DrugBank、PharmGKb数据库得到;借助cytoscape软件绘制"中药-化合物-靶点"网络;使用STRING在线平台下载靶点相互作用数据、挖掘其核心靶点;运用Bioconductor平台和R语言对药物活性成分潜在靶点网络中的蛋白进行GO和KEGG分析.结果 筛选出87个药物有效成分共涉及80个关键靶点,根据degree值展示其主要成分:槲皮素、山柰酚、柚皮素等,关键靶点包括肿瘤坏死因子、白细胞介素6等.GO功能和KEGG通路分析获得主要通路为IL-17信号通路、TNF信号通路、NF-κB信号通路等.结论 本研究从网络药理学角度预测了白芍-甘草治疗强直性脊柱炎可能的主要成分、相关靶点及信号通路,以期为后续机制研究奠定了一定的基础.

目的 采用Meta分析方法 评价系统性红斑狼疮(SLE)患者血清抗内皮细胞抗体(AECA)阳性率、优势比(OR)及探讨阳性率异质性的来源.方法 计算机联合手工规范检索建库至2020年8月1日中国学术期刊全文数据库、万方数据库、维普数据库、中国生物医学文献数据库、PubMed和Embase数据库中符合研究目的的中英文文献.根据纳入、排除标准筛选文献,采用纽卡斯尔-渥太华量表评估文献质量,提取研究数据,采用R 3.5.1软件进行Meta分析.结果 最终纳入41项研究,共有1970例SLE患者(病例组),1796例健康者(对照组).Meta分析显示,病例组血清AECA阳性率为56.4％(95％CI:48.10～64.70),I2=95.00％,高于对照组[OR=34.03(95％CI:21.79～53.14),P<0.01,I2=49.34％],异质性来源为酶联免疫吸附试验;其中,病例组血清IgG型AECA阳性数占ACEA总阳性数的58.8％(95％CI:48.10～69.50),IgA型AECA占33.2％(95％CI:26.70～39.70),IgM型AECA占12.7％(95％CI:2.60～22.70),IgG型AECA阳性数占比高于IgA型、IgM型(P<0.001);SLE患者血清AECA水平与系统性红斑狼疮疾病活动指数评分呈正相关[r=0.349(95％CI:0.23～0.46),P<0.001,I2=15.20％];狼疮肾炎患者与神经精神狼疮患者AECA阳性率差异无统计学意义(P=0.69).结论 AECA可能参与了SLE血管损害的发生发展,且血清AECA水平与SLE病情活动度相关,可用于SLE病情活动度的随访监测;SLE中以IgG型AECA升高为主,临床运用中应对其重点关注.

目的 探讨痛风患者中医证候与临床分期、实验室检查等的相关性.方法 选取2016年1月-2021年6月于云南省中医医院风湿病科住院痛风患者2 092例,收集患者临床资料、中医证候、实验室检查等.结果 本次调查显示中医证候分布依次为湿热蕴结证、寒湿痹阻证、脾虚湿阻证、痰瘀痹阻证、肝肾亏虚证、其它证型.调查发现患者年龄、发病年龄、临床分期以及实验室检查中的白介素-1β(interleukin-1β,IL-1β)、纤维蛋白原(fibrinogen,FIB)和D-二聚体与中医证型存在相关性.结论 患者的年龄、发病年龄、临床分期以及IL-1β、FIB、D-二聚体可能是造成患者中医证候差异的因素.

Background Orthosiphon stamineus Benth. (OS) was a traditional folk herb with widespread clinical application, but it was lack of comprehensive understanding of its active ingredients and polypharmacological mechanisms. The aim of this work was to systematically study its natural compounds and the molecular mechanisms of the O. stamineus via network pharmacology. Methods Compounds from O. stamineus were collected by literature retrieval and evaluated by SwissADME with the physicochemical property (ADMET model) and the likelihood for a natural medicine. The connection of active ingredients and target genes was built and confirmed by Cytoscape and AutoDock vina. Then, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were separately performed to obtain more in-depth understanding of O. stamineus. Finally, the relationship among active ingredients, targets, and diseases was built to clarify the polypharmacological mechanisms and found relevant active substances for further drug discovery. Results A total of 159 compounds of O. stamineus were collected, and 22 potentially active ingredients were screened out. The Ingredient-Target Interaction Network was built with 12 flavonoids, 3 diterpenes, 3 phenols, and 4 volatile oils, and 65 targets. The Docking analysis indicated that the ingredient-target interaction network was reliable; most ligand-receptor had a strong binding affinity (lowest binding energy: −6.9 kcal/mol). After pathway analysis, 185 significant biological processes and 36 signal pathways were found, and the ingredient-target-disease network of O. stamineus was constructed for polypharmacological mechanisms. Conclusion Our study clarified the polypharmacological mechanisms via the relationship among active ingredients, targets, and diseases and provided better guidance for subsequent experiments and potential active ingredients for drug discovery.

目的 调查住院痛风患者合并症及并发症的临床特点,并分析其影响因素.方法 采用回顾性的研究方法对2016年1月-2021年6月于云南省中医医院风湿科住院的2 087例痛风患者的人口学信息、病史、实验室检查等资料进行统计,分析合并症及并发症的分布情况及相关影响因素.结果 痛风患者合并症及并发症总的患病率为88.88％.合并症主要为代谢性疾病:高脂血症360例(17.25％)、糖尿病310例(14.85％)、脂肪肝731例(35.03％);心血管疾病:高血压1 015例(58.63％)、冠心病220例(9.85％)、冠状动脉钙化86例(4.12％);肺部损害:肺结节191例(9.15％)、肺间质纤维化35例(4.12％);其他合并症:骨关节炎667例(31.96％)、肝损伤109例(5.22％).并发病主要为肾脏疾病:肾结石389例(18.64％)、痛风性肾病244例(11.69％)、肾衰竭179例(8.58％).影响合并症和并发症发生的危险因素较多,包括年龄、职业、长病程、血沉、C反应蛋白、低密度脂蛋白、高密度脂蛋白、甘油三酯、尿酸、肌酐等.结论 痛风患者合并症及并发症发病率高达88.88％.合并症中最多见的是代谢性疾病,其中脂肪肝发病率最高;并发症以肾脏疾病最多见,以肾结石发病率最高.年龄、职业、长病程、血沉、C反应蛋白等是其重要的危险因素.

目的 基于网络药理学和分子对接探讨温阳通络方治疗类风湿关节炎(RA)的作用机制.方法 利用TCMSP数据库挖掘温阳通络方中的中药所含化学成分及作用靶点并经Uniprot数据库标准化,通过Gene-Cards 数据库获得RA相关基因,筛选出共同靶点,运用Cytoscape3.7.2软件构建活性成分-关键靶点网络,STRING数据库下载蛋白-蛋白相互作用数据,筛选相互作用图的核心靶点,利用R语言clusterProfiler包进行GO功能和KEGG通路富集分析.据化合物和蛋白的相关节点参数进行排序,对核心蛋白和活性成分进行分子对接,以及与RA临床常用治疗药物进行比较,验证网络分析结果.结果 筛选得到119个化合物及相应靶点383个,关键成分包括槲皮素、木犀草素、山柰酚等,关键靶点包括白介素6/1β、单核细胞趋化蛋白1等,与疾病靶点相映射后得到57个.GO功能富集分析,包括生物学过程1399条,分子功能60条,细胞组成22条;KEGG通路富集分析显示123条通路,主要涉及糖尿病并发症的AGE-RAGE信号通路、肿瘤坏死因子信号通路、IL-17信号通路等.分子对接表明温阳通络方关键药效分子与核心靶点有良好的结合能力,与阳性对照药物甲氨蝶呤片、来氟米特片等无明显差距,说明预测结果具有一定的可靠性.结论 温阳通络方治疗RA具有多成分、多靶点和多途径的特点,为进一步深入研究其作用机制奠定了基础.

目的 分析难治性痛风患者中医证候特点及其流行病学、病史情况、用药情况等临床特征.方法 对2016年1月-2021年6月于云南省中医医院风湿病科住院的难治性痛风患者进行回顾性分析,统计患者的性别、年龄、诱因、病程、合并症分布情况,并记录不同患者既往及院内用药情况,分析院内最常用药组合.结果 本次研究共纳入730例患者,其中男性696例,女性34例,年龄40～80岁,证候以湿热蕴结证、脾虚湿阻证、寒湿痹阻证为主.急性期多见湿热蕴结证、寒湿痹阻证,间歇期以脾虚湿阻证为主,慢性期则以痰瘀痹阻证、肝肾亏虚证为主;常合并高血压、脂肪肝、骨关节炎等病,治疗上多以中西医结合治疗为主,急性期多使用抗炎止痛药物,间歇期及慢性期以降尿酸药物为主.结论 难治性痛风患者以男性为主,具有年龄大、病程长等特点,同时容易合并其它疾病,特别是高血压、脂肪肝、骨关节炎,"痰瘀"是发病的关键病机.

目的 研究益气养血方对膝骨关节炎模型大鼠软骨BMP-2、BMP-4蛋白及mRNA表达的影响.方法 105只SD雌性大鼠随机分为7个组:空白对照组、假手术组、模型组、阳性对照组(双氯芬酸钠肠溶片混悬液4mg·kg-1 ·d-1)、益气养血方低(1.89 g·kg-1·d-1)、中(3.78 g·kg-1·d-1)、高(7.56 g· kg-1·d-1)剂量组,每组15只.空白对照组不予任何处理,假手术组切开关节囊后缝合,其余各组均采用改良Hulth法构建大鼠膝骨关节炎模型.用药处理8周后取右膝关节软骨进行HE染色及病理评分,应用免疫组化法检测模型组及益气养血方中剂量组软骨组织中BMP-2、BMP-4蛋白的表达应用PCR法测定BMP-2、BMP-4 mRNA水平.结果 与模型组相比,益气养血方各组及阳性药物组对关节软骨病理损伤(P ＜0.05,P＜0.01)有保护作用;益气养血方中、高剂量组病理评分(P＜0.05,P＜0.01)与软骨组织中BMP-2、BMP-4mRNA的表达水平低于阳性组(P＜0.05,P＜0.01).与模型组对比,益气养血方中剂量组BMP-2、BMP-4的蛋白表达降低.结论 益气养血方通过抑制BMP-2、BMP-4mRNA和蛋白的表达而对大鼠软骨组织有保护作用.