Connective tissue disease-associated interstitial lung disease (CTD-ILD) is a systemic autoimmune disease with high morbidity and hazard, characterized by progressive pulmonary inflammation and fibrosis. The monomer formulation of polydatin and curcumin (PD + Cur) for lung injury in CTD-ILD was optimized from Curcumae Longae Rhizoma (Curcuma Longa L.) and Polygoni Cuspidati Rhizoma Et Radix (Polygonum cuspidatum Sieb. et Zucc.). Mice with CTD-ILD-like lung injury were established by a single intratracheal drip of bleomycin. After intervening in model mice for 4 weeks, PD + Cur attenuated alveolar atrophy, fibrillar collagen formation, and thickened alveolar septa in the lung, improved serum biomarkers TOLLIP, MUC5B, KL-6, SP-D, and RCN3, and suppressed serum immunoinflammatory factors IL-6, CCL-18, and SF. The transcriptome sequencing showed that PD + Cur ameliorated CTD-ILD mainly by regulating aberrant immunoinflammation, which was further confirmed by proteomics that the PI3K/AKT/TGF-β pathway was a key pathway. Further, PD + Cur was found to affect amino acid metabolism in the serum significantly. The B-type receptor for GABA (GABBR) agonist baclofen was further found to attenuate CTD-ILD-like lung injury and modulate PI3K/AKT/TGF-β signaling. However, the inhibition of AKT, transforming growth factor beta receptor type 3 (TGFβR3), a key indicator downstream of PI3-kinase subunit p85-alpha (PI3KR1), by PD + Cur was reversed after intervention with the GABBR receptor inhibitor CGP52432. PD + Cur has an ameliorative effect on CTD-ILD-like lung injury by targeting GABBR to modulate the PI3K/AKT/TGF-β pathway.

Ethnopharmacological relevance: Recently, interstitial lung disease (ILD) morbidity and mortality have been increasing with insidious epidemiological characteristics. Jianghu decoction (JH) is an effective Chinese medicine for ILD.Aim of the study: We aimed to reveal the material basis and mechanism of action of JH in the treatment of ILD. Materials and methods: In this study, an ILD mouse model was constructed with bleomycin. HE staining, transcriptome analysis, parallel reaction monitoring-mass spectrometry (PRM-MS), UPLC-MS, and western blotting assays were conducted.Results: HE staining results showed that JH effectively reduced inflammation and fibrosis foci in the lungs of the ILD model. Furthermore, transcriptome analysis revealed that JH regulates a set of biological signaling pathways related to immune inflammation and fibrosis. PRM-MS combined with western blotting was applied to detect inflammation and fibrosis involving proteins in lung tissue. JH effectively reversed the aberrant expression of HMGB1, RAGE, SEPTIN4, ACTA2, and ITGAV proteins in the model group. AMPK was identified as the core upstream regulatory protein for JH-mediated ILD regulation. In addition, UHPLC-MS technology was applied to determine the active ingredients of JH. A total of 80 components were identified from JH, and polydatin (PD) was identified as the active ingredient that effectively alleviated lung fibrosis and inflammatory injury in ILD mice. To illustrate the molecular regulatory network of JH and PD in alleviating lung fibrosis and inflammatory injury, we also examined inflammation and fibrosis-related molecules downstream of the AMPK pathway with RT-qPCR and western blotting.Conclusions: The results showed that both JH and its active component PD exert synergistic inhibition on pulmonary fibrosis and inflammation. Specifically, the AMPK/PGC1 & alpha;/PPAR & gamma; signaling pathway was activated, and the AMPK/HMGB1/RAGE signaling pathway was inhibited in ILD lungs responding to JH or PD administration.

"阳化气,阴成形"是对阴阳生理功能的高度概括,阳推动有形阴精弥散为无形之气以实现脏腑功能,阴凝聚无形之气为有形阴精而滋润周身内外,二者在相互制约中维持动态平衡,其中阳化气在该过程中占据主导地位.系统性硬化症(systemic sclerosis,SSc)属于中医"皮痹"范畴,全程分为水肿期、硬化期和萎缩期,病程中常易累及心、肺、肾、胃肠道等脏腑.阳化气不足是SSc发病的根本原因,以肺脾肾三脏阳气亏虚为主,脏腑功能减退,有形阴邪凝聚过多,阴成形太过是SSc发展的必经环节.治疗以温阳化气、化痰祛瘀为原则,温补与温通共施,促进气化,振奋脏腑机能,助阴翳消散;祛瘀化痰治其标证,助阳气通达.扶阳、抑阴二法贯穿疾病始终,相辅相成.又因疾病分期中存在脏腑、虚实等主次之别而各有侧重,同时兼顾养阴以荣润肌肤、阴中求阳.病理上阳化气不足促使阴成形过度,阴成形太过又阻碍阳化气过程,二者形成恶性循环,导致SSc的发生发展.治疗上扶阳为主导,打破恶性循环,兼能抑阴,抑阴又能扶阳,二法形成正向循环,使得阳气复、阴凝散,改善患者症状、延缓病情进展.

张春艳主任医师认为类风湿关节炎活动期多见湿热痹阻证,湿热邪气是其发生的根源,经络闭阻、气血阻滞是病机本质,二者共同组成该病的核心病机.临证常运用吴鞠通《温病条辨》中宣痹汤为底方,清热祛湿为主,宣气化湿、通达经络为辅,共奏清湿热、开郁结、通经络之功,且不拘泥于原方,随证化裁,制方出新.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare chronic inflammatory disease. The main clinical manifestation of SAPHO syndrome is an osteoarthropathy with cutaneous involvement. Relapsing polychondritis (RP) characterized by chronic inflammation and cartilage degeneration is a rare systematic autoimmune disease. Here we report a RP case in a SAPHO syndrome patient, in which auricularitis happened 10 years after the diagnosed as SAPHO syndrome. Tofacitinib treatment can alleviate the symptoms.

Rheumatoid arthritis (RA) is an autoimmune disease that is associated with burdened personal, social, and economic costs. Enhanced understanding of RA pathogenesis and the development of effective therapies is pressingly needed. Seeking effective solution for diseases from natural medicine has become an attractive point of providing a new perspective for drug development. Polydatin (PD) has been found to be beneficial to arthritis. However, the pharmacological action of PD is weak in clinical practice due to poor aqueous solubility, chemical instability in aqueous alkaline medium, and extensive first-pass metabolism. Biodegradable nanoparticle, which is of better solubility and lower degradation, could be a good choice for PD targeted delivery to overcome these obstacles. With advantages in straightforward synthesis,1-3 mesoporous silica nanoparticles (MSNs) were chosen for developing an efficient and safe nanocarrier for PD in this study. We developed PD@MSN-FA/RGD (Figure 1A, Figures S1–S8, Table S1) as a dual-target nano-drug delivery system that aimed at folate receptor and ανβ3 integrin receptor. Drug release profiles of PD@MSN-FA/RGD were illustrated to be sustained and mass ratio dependent (Figure 1B). To further evaluate the possibility of in vivo application of PD@MSN-FA/RGD, the hemolysis test was performed in vitro and in vivo. No significant difference was observed between MSN and control (-) samples. It was demonstrated that no false negative or false-positive results, which could be caused by adsorption of hemoglobin on particle surfaces4 or toxicity of the residual surfactant,5 occurred in hemolysis assay of PD@MSN-FA/RGD. No significant hemolysis occurred with the concentration below 13.80 mg/ml, and excellent biocompatibility was displayed with the concentration below 4.60 mg/ml in vitro (Figure 1E and F). Likewise, no hemolysis effect of PD@MSN-FA/RGD was observed with dosage below 438.28 mg/kg in mice (Table S2). Moreover, no significant acute toxicity was observed in mice subjected to PD@MSN-FA/RGD administration (Table S3, Figure S9) except for slight or local liver lesions, including diffuse swelling (Figure S9B5) and local necrosis (Figure S9B3 and B4) in some samples. How these lesions being induced deserved further investigation. In addition, the performance of PD@MSN-FA/RGD in vivo was illustrated by employing a selective ion monitoring model in UHPLC-Q-Exactive Orbitrap MS. It displayed an extremely low content of PD@MSN-FA/RGD in tissues except plasma, synovial fluid, and synovial membrane, suggesting a significantly targeted delivery of PD@MSN-FA/RGD injection comparing with that of polydatin injection (Figure 1C and D, Figure S10). No significant degradation product was detected in the liver upon PD@MSN-FA/RGD injection, suggesting a lower degradation of PD with nanoparticles embedding (Figure S11). In the collagen-induced arthritis (CIA) model, joint damages were observed significantly improved upon PD@MSN-FA/RGD treatment based on vertical and horizontal diameters of hind legs and ankle joints, the thickness of footpads, as well as histopathology changes in synovial membrane and cartilage tissue (Figure 2, Tables S4–S10). The metabolic profile of PD@MSN-FA/RGD in synovial fluid was further studied. PCA and OPLS-DA results showed the availability of CIA modeling as well as the significant influence of PD@MSN-FA/RGD (R2X = 0.62, R2Y > 0.6, Q2 > 0.6) (Figure S12). Note that 115 molecules were identified from 187 ions that contributed to good separations among groups (VIP > 1 in ESI+, p < 0.05). Among the metabolites identified, 26 were found upregulated and 2 were downregulated responding to CIA modeling and significantly reversed by positive drug methotrexate and PD@MSN-FA/RGD treatment (Table S11, Figure S13). Moreover, metabolomics analysis was performed by employing IPA software. High-dose and low-dose PD@MSN-FA/RGD treatment showed compatible metabolism on the CIA model (Figure 3A and B). Numerous metabolic pathways shifted toward rheumatoid arthritis-related intermediates and metabolic endpoints were suggested by pathway analysis (Figure 3C and D). Moreover, dramatical downregulation of PD@MSN-FA/RGD on D-serine, guanine, and hypoxanthine (Figure 3E–G) indicated a strong inhibition of fibroblasts proliferation. With changes in guanine, d-serine, l-arginine, choline, kynurenic acid, and 5-methylcytosine, it was suggested that mitogen-activated protein kinase (MAPK) family proteins playing key roles in PD@MSN-FA/RGD regulation (Figure 3I). Increased expression of p38 MAPK, a crucial molecule in the progression of RA,6 was found significantly inversed upon administration of PD@MSN-FA/RGD in synovial tissues (Figure 3L, P, and S). Moreover, we found δ-guanidinovaleric acid (Figure 3H), aγ-aminobutyric acid (GABA)-receptor antagonist, increased significantly responding to CIA modeling, suggesting inhibition of GABA receptor. These changes were reversed by PD@MSN-FA/RGD administration, suggesting the promotion on GABA signaling. Based on the effect of inhibited p38 MAPK on joint inflammation, and the inhibitory role of GABA in p38 MAPK signaling, a hypothesis7 was proposed that GABA may downregulate p38 MAPK activity to suppress inflammation in RA. How does PD@MSN-FA/RGD suppress fibroblasts proliferation via the GABA-p38 MAPK pathway? To address this question, a transcriptomic study was carried out. Pathway analysis showed that GABA-p38 MAPK signaling is significantly regulated by PD@MSN-FA/RGD, consistent with that of metabolome study (Figure 3J). Intriguingly, myocardin-related transcription factor A (MRTFA), myocardin-related transcription factor B (MRTFB), and serum response factor (SRF) that played key roles in fibroblast activation were predicted as potential upstream regulators in PD@MSN-FA/RGD's regulation (Figure 3K). Upregulated mRNA expressions of MRTFA, MRTFB, and SRF in the CIA model were found reversed with PD@MSN-FA/RGD in synovial tissues to different extents (Figure 3L–O). Similar regulations were also observed at the protein level (Figure 3P–S). p38 MAPK cascades could promote the formation of ternary nucleoprotein complex and activate the early response gene transcription initiated by SRF.8 SRF functions in partnership with MRTFA/B and acts as a key mediator in fibroblasts activation.9, 10 Taken together, it was suggested that PD@MSN-FA/RGD alleviated inflammation and fibroblasts proliferation in RA by regulating GABA-p38 MAPK-MRTFs/SRF signaling pathway (Figure 4). In this work, a folate/RGD-dual-functionalized mesoporous silica nanoparticles (MSNs-FA/RGD) with reproducible and stable production, as well as good biocompatibility, was developed to carry PD to the synovial area to achieve promising clinical translation and application in RA therapy. Protective effects of PD@MSNs-FA/RGD on rheumatoid arthritis were illustrated with CIA modeling rats. PD@MSNs-FA/RGD was found targeting on GABA-p38 MAPK-MRTFs/SRF signaling pathway in vivo to exert its beneficial influence. We reported a novel drug of RA with both characterization and regulatory mechanism carefully discussed and clarified. This research was funded by the National Natural Science Foundation of China (51772032). The authors have declared no conflict of interest. Figure S1. (A and B) TEM images of MSNs, and it was observed that MSNs are spherical nanoparticles with a diameter of about 80 nm. Figure S2. Hydrodynamic diameter (A) and Zeta potential (B) of MSNs. The average hydrodynamic size of MSNs is 277.5 nm and their surface charge is 28.9 mV. Figure S3. SEM (A) and TEM (B) images of MSNs. SEM (C) and TEM (D) images of MSN-NH2. No significant influence of -NH2 modification on the spherical morphology, size, as well as mesoporous property of MSNs was observed. Figure S4. Zeta potential of MSN-NH2. The surface charge is about 16.9 mV. Figure S5. The FTIR spectra of MSNs and MSN-NH2. A new FTIR spectra band appeared at 3421 cm-1 after modification due to the stretching vibration of -NH2 groups. Figure S6. The linear relationship between the concentration of PD and their optical absorption intensity. The fitted linear equation is y = 0.04009 + 0.02998x, R2 = 0.99897. Figure S7. (A) N2 adsorption-desorption isotherms and (B) pore-size distributions of MSNs. (C) N2 adsorption-desorption isotherms and (D) pore-size distributions of PD@MSNs. Figure S8. (A) UV-Vis spectra of PD@MSN-NH2, NHS-PEG-FA, PD@MSN-FA/SH. (B) Zeta potential of PD@MSN-NH2, PD@NHS-FA/SH, PD@MSN-FA/RGD. Figure S9. H&E staining of pathological changes in response to different dosages of PD@MSN-FA/RGD after 14 days’ administration. Figure S10. UPLC-Q exactive quantitative analysis of polydatin in plasma, heart, liver, spleen, kidney, synovial fluid, and synovial membrane tissue of rats which subject to PLN injection based on selective ion monitoring (SIM)-based method. Figure S11. Metabolic trait of polydatin in vivo. 7 major metabolites generated from polydatin degradation were detected in the liver of rats which subject to polydatin injection, while none significant degradation product was detected upon PD@MSN-FA/RGD injection. Figure S12. Multi-dimensional statistics of metabolomics data. A–B. PCA analysis based on LC-MS data obtained from synovial fluid of Control, Model, Positive, high-dose PLN, and low-dose PLN group. (A) Result based on HILIC mode data; (B) Result based on RP-C18 mode data; C-H. OPLS-DA on LC-MS data of common metabolites of the control group, model group, positive group, high-dose PLN group, and low-dose PLN group. (C, F) Control vs. Model groups under HILIC and RP-C18 mode. (D, G) Model vs. high-dose PLN groups under HILIC and RP-C18 mode (E, H) Model vs. low-dose PLN groups under HILIC and RP-C18 mode; I-N. Robustness assessments of OPLS-DA model. Figure S13. Hierarchical clustering analysis on common differential metabolites detected and identified in each group. Table S1. The loading content and entrapment efficiency of PD@MSN and PD@MSN-NH2. Table S2. OD values of serum in mice subjecting to different dosages of PD@MSN-FA/RGD. Table S3. Organ coefficients of heart, liver, spleen, lung, and kidney in mice subjecting to different dosages of PD@MSN-FA/RGD. Table S4. Horizontal diameters of right hind legs (mm) Table S5. Vertical diameters of right hind legs (mm) Table S6. Horizontal diameters of left hind legs (mm) Table S7. Vertical diameters of left hind legs (mm) Table S8. Thickness of right hind footpads (mm) Table S9. Thickness of left hind footpads (mm) Table S10. Vertical and horizontal diameters of left/right ankle joints Table S11. Differential metabolites being detected and identified. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

白塞病是一种慢性全身性血管炎症性疾病.目前中医多从湿热毒瘀论治白塞病,日久易损伤脾肾之阳,形成虚阳上浮,上热下寒的病机,宜选潜阳封髓丹以扶阳抑阴,引火归元.

目的 通过观察藤莓汤(Tengmei Decoction,TMD)对胶原诱导性(collagen-induced arthritis,CIA)大鼠滑膜中突变型P53 (Mutant P53,mt-p53)、增殖诱导配体(a proliferation-inducing ligand,APRIL),白细胞介素2 (Lnterleukin 2,IL-2)表达的影响,探讨藤莓汤抑制类风湿关节炎(rheumatoid arthritis,RA)滑膜免疫炎性损伤的分子机制.方法 建立CIA大鼠模型,中药给药组分为TMD高剂量组、TMD低剂量组,分别以TMD生药量31.8、15.9g/(kg·d-1)灌胃;模型组、阳性对照组分别予去离子水10 mL/(kg·d-1)、来氟米特1.87mg/(kg-1·d-1)灌胃;另设正常对照组,予去离子水10 mL/(kg·d-1),各组连续干预12周.干预结束后检测mt-P53、APRIL、IL-2蛋白及mRNA表达.结果 与正常组比较,模型组APRIL、mt-P53、IL-2 mRNA转录水平上调(P＜0.01);mt-P53、IL-2蛋白表达上调(P＜ 0.01,P＜0.05).与模型组比较,各治疗组APRIL mRNA转录水平,mt-P53、IL-2mRNA转录水平及蛋白表达水平下调,(P＜ 0.01,P＜0.05);结论TMD能够降低大鼠关节滑膜、血清中mt-P53、IL-2、APRIL表达水平,改善关节炎模型大鼠关节滑膜免疫炎性损伤,可能与TMD抑制关节滑膜过度增殖,降低炎症因子的表达有关.

目的 观察秦苓液对尿酸性肾病大鼠过氧化物酶体增殖物激活受体 γ 辅助激活因子-1α(peroxi-some proliferator activated receptor coactivator-1 alpha,PGC-1α)、白介素-1β(interleukin beta,IL-1β)、受激活调节正常T细胞表达和分泌因子(regulated upon activation normal T cell expressed and secreted factor,RANTES)的影响.方法采用腺嘌呤灌胃伴酵母饲料喂养大鼠的方法进行造模,成模后随机分为模型组,阳性药物组,秦苓液大、中、小剂量组,每组12只大鼠.选6只正常大鼠作为正常对照组.各组分别用药连续干预6周和8周后采用实时荧光定量逆转录聚合酶链反应(real time reverse transcription-polymerase chain reaction,RT-PCR)、蛋白免疫印迹法(Western blot)、免疫组化和酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)检测大鼠PGC-1α、IL-1β、RANTES基因和蛋白表达水平.结果与正常对照组比较,6周时和8周时模型组PGC-1α 蛋白表达水平及8周时PGC-1α基因转录水平显著下调,6周时IL-1β基因转录、蛋白表达水平和RANTES蛋白表达水平及8周时两者水平显著上调(P<0.05,P<0.01).与模型组比较,6周时秦苓液各剂量组PGC-1α蛋白表达水平及8周时中、小剂量组PGC-1α基因水平及蛋白表达水平显著上调,6周时秦苓液各剂量组IL-1β基因转录及大、中剂量组IL-1β蛋白表达水平以及各剂量组RANTES蛋白表达水平显著下调,8周时秦苓液小剂量组IL-1β及中、小剂量组RANTES基因转录及中、小剂量组IL-1β、RANTES蛋白表达水平显著下调(P<0.05,P<0.01).结论秦苓液抑制UN模型大鼠免疫炎性损伤,其分子机制可能与上调PGC-1α的水平,抑制IL-1β、RANTES的生物学活性有关.

目的:通过观察虎杖对胶原诱导性关节炎(CIA)模型大鼠滑膜组织、血清中抑癌基因p53突变型(mt-p53)、增殖诱导配体(APRIL)、肿瘤坏死因子-α(TNF-α)表达的影响,探讨虎杖抑制类风湿关节炎滑膜免疫炎性损伤的作用机制.方法:采用大鼠尾根部注射牛Ⅱ型胶原方法制备CIA模型,将成模大鼠按随机数字表法分为模型组、阳性对照组、虎杖2倍剂量组、虎杖常量组,另设正常对照组,每组6只.正常对照组与模型组予去离子水10mL·kg-1·d-1灌胃,阳性对照组予来氟米特1.87mg·kg-1·d-1灌胃,虎杖2倍剂量组、虎杖常量组分别以虎杖颗粒8、4g·kg-1·d-1灌胃,连续干预12周.观察各组大鼠偶数周体质量、AI评分及各组大鼠滑膜组织中APRIL、mt-p53、TNF-αmRNA,mt-p53、TNF-α蛋白及血清中TNF-α蛋白表达情况.结果:与正常对照组比较,模型组大鼠体质量及AI评分有明显变化(P＜0.05,P＜0.01);与模型组比较,各治疗组大鼠体质量及AI评分有明显改善.与正常对照组比较,模型组APRIL、mt-P53、TNF-α mRNA转录水平显著上调(P＜0.01),mt-P53、TNF-α蛋白表达水平显著上调(P＜0.01);与模型组比较,各治疗组APRIL、mt-p53、TNF-αmRNA转录水平显著下调(P＜0.01);mt-p53、TNF-α蛋白表达水平显著下调(P＜0.01).结论:虎杖改善CIA大鼠关节滑膜免疫炎性损伤的机制可能与抑制滑膜细胞增殖相关.

The aim of the present study was designed to investigate that Platycodon grandiflorum saponins (PGS) exerted protective effects against testicular injury induced by scrotal hyperthermia. PGS (15, 30 mg/kg) were administered intragastrically to mice for 14 days, then exposed to a single scrotal heat treatment at 43 °C for 18 min on the 7th day. Heat stress (HS) induced spermatogenic damage was associated with a significant loss of leydig cells and the changes of serum testosterone, oxidative stress and apoptosis markers, and activated MAPK signaling pathway. In contrast, PGS treatment normalized HS-induced histopathological changes and prevented the activation of MAPK signaling pathway, which was contributed to oxidative stress and apoptosis in the testis of treated mice. In conclusion, our findings clearly demonstrated that PGS exhibited a significant protective effect against HS-induced testicular dysfunction, largely dependent upon the inhibition of oxidative stress associated apoptosis via partly regulation of MAPK signaling pathway.

To investigate the nature and class of association forces between the pure liquids and their liquid mixtures, we have been analyzed with excess thermodynamic properties, spectroscopic and computational techniques. Although, the thermodynamic parameters such as excess volume (VE), isentropic compressibility (ks) and excess isentropic compressibility (ksE) have been calculated using the experimental data of density (ρ) and speeds of sound (u) of o-cresol with 1-alkanols (C3–C8) namely, 1-propanol, 1-butanol, 1-pentanol, 1-hexanol, 1-heptanol and 1-octanol at different temperatures from 25 to 40 °C with interval of 5 °C and at 0.1 MPa. The calculated excess and deviation functions have been fitted to the Redlich-Kister polynomial equation and the results have been analyzed in terms of molecular interactions and structural effects. However, the FT-IR data strongly supports the presence of intra- and inter molecular interactions between component molecules in the liquid mixtures through changing the stretching vibrational frequency of various functional groups of pure liquids. In addition, the hydrogen bonding features between o-cresol with different 1-alkanols were examined by using a molecular modeling program with the help of density functional theory (DFT - B3LYP), the optimized geometries, bond characteristics, natural bond orbital (NBO) and interaction energies of pure components and their complexes have been analyzed theoretically to recognize the nature and strength of interactions between o-cresol and 1-alkanols.

目的 通过观察虎杖对胶原诱导性关节炎(CIA)大鼠踝关节病理及滑膜组织、血清中过氧化物酶体增殖物激活受体-γ(PPARγ)、p65、白细胞介素17(IL-17)表达的影响,探讨虎杖抑制类风湿关节炎(RA)滑膜免疫炎性损伤的作用机制.方法 采用大鼠尾根部注射牛CⅡ方法制备CIA模型,将成模大鼠按随机数字表法分为模型组、阳性对照组、虎杖2倍剂量组、虎杖常量组,另设正常对照组,每组6只.正常对照组与模型组每天予去离子水10 mL/kg灌胃,阳性对照组每天予来氟米特1.87 mg/kg灌胃,虎杖2倍剂量组、常量组每天分别以8、4 g/kg灌胃,连续干预12周.采用光镜观察各组大鼠踝关节病理改变.运用RTPCR、Western Blot及ELISA检测技术,观察各组大鼠滑膜组织、血清中PPARγ、p65、IL-17 mRNA及蛋白表达情况.结果 与正常对照组比较,模型组大鼠踝关节关节周围纤维组织增生,炎性细胞浸润;与模型组比较,虎杖常量组大鼠关节软骨、关节腔未见明显病变.与正常对照组比较,模型组PPARγ、p65、IL-17 mRNA及蛋白表达上调(P＜0.01).与模型组比较,虎杖2倍剂量组及常量组p65、IL-17 mRNA及蛋白表达均下调(P＜0.01);PPARγ mRNA蛋白表达水平上调(P＜0.01).结论 虎杖改善CIA模型大鼠关节滑膜免疫炎性损伤的机制,可能与调节PPARγ/NF-κB信号途径相关.

To observe the effects of Chinese medicine (CM) Polygonum cuspidatum (PC) on adenosine 5′-monophosphate-activated protein kinase (AMPK), forkhead box O3α (FOXO3α), Toll-like receptor-4 (TLR4), NACHT, LRR and PYD domains-containing protein 3 (NLRP3), and monocyte chemoattractant protein-1 (MCP-1) expression in a rat model of uric acid-induced renal damage and to determine the molecular mechanism.

目的 分析雷公藤多甙致粒细胞缺乏病例的临床资料,以提高临床对使用雷公藤多甙不良反应的认识.方法 回顾性分析本院风湿科于2018年3月收治的1例使用雷公藤多甙片治疗自身免疫性疾病时出现急性粒细胞缺乏病例的临床资料,并结合近30年国内文献报道的22例资料较全的类似病例进行分析.结果 患者,女,72岁,入院诊断为结缔组织病,常规治疗加用小剂量雷公藤多甙片(20mg/次,3次/天,总剂量60mg)立即出现急性粒细胞缺乏,停用雷公藤多甙片后粒细胞计数逐渐恢复正常.文献复习发现,雷公藤制剂不良反应的发生与患者年龄、给药剂量和用药时间有关.不良反应多发生于15～40岁的患者,随着年龄的增大,不良反应的发生率逐渐降低.不良反应多发生在给药剂量为60～90mg/d时,小剂量用药时发生率明显较低.不良反应多发生在用药1～3周内,用药时间久者,不易发生不良反应.结论 短期小剂量使用雷公藤多甙片治疗自身免疫性疾病时可引起急性粒细胞缺乏的发生,停药后可缓解.临床使用雷公藤多甙时,除关注给药剂量、用药时间及患者年龄外,还应注意个体易感因素,并定期监测血常规和肝肾功能,以防止不良事件的发生.

强直性脊柱炎( ankylosing spondylitis, AS)是一种原因不明的,以骶髂关节及脊柱中轴关节为主要病变部位的炎症性疾病,其主要病理改变是肌腱、韧带及骨附着点炎症. AS患者常常出现腰背部僵直和疼痛,夜间痛明显,活动后症状缓解,疾病发展最终导致关节畸形、活动受限甚至功能障碍. AS多见于青壮年,发病年龄多在10～40 岁,男性发病率明显高于女性,目前我国患病率约为0. 3％ [1].

Objective] To explore the effect of modified Simiao Yong’an decoction on collagen induced arthritis about arthritis index (AI), the joint tissue inflammatory pathological manifestations, and effect on protein expression of IL-6,IL-17,TNF-αin rats. [Methods] The successful CIA models of SD rats were randomly divided into model group, positive group (leflunomide), and high, medium, low dose group of Chinese medicine, and normal control group, 6 rats in each group. The intervention and treatment period was 12 weeks. AI val-ues of each rat were evaluated every week. At 12 weeks, rats were executed and right ankle joint of each group of rats was taken. Joint pathlological changes of each right ankle were observed. At the same time levels of IL-6, IL-17 and TNF-αin serum were examined by ELISA, mRNA transcription levels of IL-6, IL-17and TNF-αin synovial were detected by RT-PCR. [Results] AI scores of the three Chi-nese medicine groups decreased significantly (P﹤0.05 or P﹤0.01) in 6~12 weeks compared with the model group, and in the 8~10 weeks AI scores were even improved significantly than positive group (P﹤0.05 or P﹤0.01). Histological examination showed that the ankle joint cartilage pathological had an improvement in the medium dose of modified Simiao Yong’an decoction group compared with the control model group. Compared with the model group, mRNA and protein expression of IL-6, IL-17and TNF-αwere down regulated in all treat-ment groups significantly (P﹤0.01). [Conclusion] The anti-inflammatory action mechanism on CIA rats of modified Simiao Yong’an de-coction might achieve by reducing expression of IL-6, IL-17 and TNF-α.

OBJECTIVE:To observe the clinical efficacy and safety of Shuanghu Qinggan Granule ( , SQG) plus Yigan Yiqi Jieyu Granule (, YYJG) combined with lamivudine (LAM) on chronic hepatitis B (CHB) patients.METHODS:The study was a multicenter, randomized, double-blinded and parallel controlled trial. A total of 320 patients were randomly allocated into 2 groups equally: 160 patients (treatment group) were given SQG and YYJG combined with LAM; and 160 patients (control group) were given LAM plus Chinese herb placebo, respectively. Liver functions, hepatitis B envelop antigen (HBeAg) titer levels, and hepatitis B virus DNA (HBV-DNA) load were monitored.RESULTS:(1) In the 48th week, the treatment group showed superior HBeAg seroconversion rate than that in the control group (38.0% vs. 24.0%, P<0.05). (2) In the 48th week, the treatment group demonstrated lower HBeAg titer than that in the control group (P<0.05). (3) In the 12th, 24th, 48th week, there was no statistical significance in HBV-DNA response rate between the two groups. (4) In the 12th week, the level of glutamyl transpeptidase (GGT) was significantly decreased in the treatment group compared with the control group (P<0.05); in the 36th week, the levels of alanine aminotransferase and aspartate transaminase were significantly lower in the treatment group than those in the control group (P<0.05).CONCLUSION:The protocol of SQG and YYJG combined with LAM to treat CHB showed superior efficacy than LAM monotherapy.