Rheumatoid arthritis (RA) is characterized by elevated levels of reactive oxygen species (ROS) and a persistent inflammatory microenvironment dominated by M1 macrophages, both of which contribute to disease progression. To address these pathological features, we developed a core-shell nanoplatform consisting of silver-modified ceria nanoparticles loaded with celastrol (Ag-CeNP@Cel). This nanoplatform significantly enhances the water solubility of celastrol and reduces its hepato-renal toxicity by enabling passive accumulation in inflamed joints. The silver-modified ceria nanoparticles synergistically combine with celastrol to scavenge excess ROS and reprogram M1 macrophages into M2 macrophages, thereby mitigating inflammatory responses and improving the rheumatoid arthritis microenvironment (RAM). Ag-CeNP@Cel exhibited robust therapeutic efficacy and safety in preclinical models, presenting an innovative approach to RA treatment by integrating ROS elimination with macrophage modulation to ameliorate inflammatory microenvironment. This study underscores the potential of Ag-CeNP@Cel as a promising therapeutic strategy for RA management.

Hyper-uric acid (UA)-induced kidney injury (HAKI) is caused by the deposition of excess blood UA into the kidneys. We confined molecules of uricase (URI), catalase (CAT), and curcumin (Cur) to a single structure (UC/Cur) while retaining their enzymatic activities via a cross-linking complexation reaction between tannic acid and FeCl3 for treating HAKI. Simultaneously, bovine serum albumin (BSA)-UC/Cur nanoparticles were successfully prepared by interlinking the disulfide bonds of BSA with the enzyme complex via Tris(2-carboxyethyl) phosphine(TCEP) to form sulfhydryl groups. BSA-UC/Cur significantly attenuated MSU-induced NLRP3 inflammasome pathway activation and apoptosis in NRK-52e cells by eliminating UA crystals and intracellular reactive oxygen species. More importantly, treatment with BSA-UC/Cur stabilized blood UA concentrations and lowered proximal tubular protein levels, mitochondrial swelling, and fibrotic areas, renducing the expression of matrix metalloproteinase (MMP)2, MMP9, and NLRP3 while, increasing the expression of tight-junction proteins ZO1 and occludin as well as that of TIMP-1, in HAKI model rats. In addition, BSA-UC/Cur nanoparticles reduced the subpopulation ratios of CD8+ T cells and M1 macrophages and increased those of M2 macrophages and Treg cells. Preliminary in-vivo trials showed that long-term intravenous treatment with BSA-UC/Cur is safe. Therefore, BSA-UC/Cur could be a potential nanotherapeutic agent for HAKI.

The marketed paclitaxel (PTX) formulation Taxol relies on the application of Cremophor EL as a solubilizer. The major drawback of Taxol is its hypersensitivity reactions and a pretreatment of anti-allergic drugs is a necessity. Therefore, developing an efficient and safe delivery vehicle is a solution to increase PTX treatment outcomes with minimal adverse effects. In this work, we prepared the amphiphilic peptides (termed AmP) from soybean proteins using a facile two-step method. AmP could efficiently solubilize PTX by self-assembling into mixed micelles with D- alpha-tocopherol polyethylene glycol succinate (TPGS), a common pharmaceutical expedient (PTX@TPGSAmP). The intravenously administrated PTX@TPGS-AmP exhibited a slow clearance (0.24 mL & sdot; (min & sdot; kg) - 1 ) and an enhanced AUC (41.4 mu g.h/mL), manifesting a 3.6-fold increase compared to Taxol. In a murine 4T1 tumor model, PTX@TPGS-AmP displayed a superior antitumor effect o v er Taxol. Importantly, safety assessment showed a high biocompatibility of AmP and an i.v. dose up to 2500 mg/kg led to no observable abnormalities in the mice. In summary, the AmP presents a new green and easily-prepared amphiphilic biomaterial, with promising potential as a pharmaceutical excipient for drug delivery.

目的:基于数据挖掘研究欧阳惠卿教授治疗痛经的用药规律.方法:收集广州中医药大学第一附属医院全国名中医欧阳惠卿教授门诊的痛经病例,按纳入标准、排除标准进行筛选,建立欧阳惠卿痛经病例数据库,运用中医传承辅助平台V3.0 的统计分析及方剂分析功能对其进行数据挖掘.结果:共纳入 51 个病例,涉及 69 种中药,药物四气以温性为主,其次为平性、寒性,五味以为辛、苦、甘为主,归经以脾、肝、胃为主,功效以理气、补虚、活血化瘀类为主,使用频次≥5 的高频药物共 31 种,其中最核心的药物为木香,使用频次≥25 的药物组合共 16 个,其中含木香的组合共 11 个,运用聚类分析得到可能的新方组合 3 首.结论:欧阳惠卿教授善用木香治疗女子痛经,处方用药顺应气血喜温恶寒的生理,以辛温苦甘为主,忌用大寒大热之品.

Object: Menopause is linked to a higher risk of cardiovascular disease. However, it is unclear whether premature menopause (defined as menopause before the age of 40 years) or early menopause (defined as menopause before the age of 45 years) is associated with an increased risk of heart failure or atrial fibrillation. This study aimed to examine the most reliable evidence on the relationship between early menopause and the risk of heart failure and atrial fibrillation.Methods: A comprehensive literature search was performed in three online databases, Embase, Web of Science, and PubMed, from database establishment to April 1, 2023. The results were presented as hazard ratios with 95 % confidence intervals. The I2 statistic was employed to assess heterogeneity, and the Egger's test was used to determine publication bias.Results: Nine cohort studies were included in the analysis, with a total of 6,255,783 postmenopausal women. Women with premature and early menopause had an increased risk of heart failure (HR: 1.39, 95 % CI: 1.31-1.47; HR: 1.23, 95 % CI: 1.10-1.37, respectively) and atrial fibrillation (HR: 1.15, 95 % CI: 1.01-1.31; HR: 1.08, 95 % CI: 1.04-1.13, respectively) when compared with women who had undergone menopause after the age of 45 years. Subgroup analysis showed that, compared with early menopause, premature menopause has a stronger association with an increased risk of heart failure and atrial fibrillation.Conclusions: Women who undergo premature menopause or early menopause have a higher risk of heart failure and atrial fibrillation compared with women who undergo menopause in the normal age range. These repro-ductive factors need to be considered for measures that might reduce the risk of heart failure and atrial fibrillation.

BackgroundTransition into menopause is associated with an increased risk of cardiovascular disease (CVD). However, it is unclear whether the association exists between premature menopause (defined as age at menopause 40 years) or early menopause (defined as age at menopause 40–45 years) and CVD or cardiovascular risk factors. The aim of this review was to comprehensively evaluate and meta-analyze the most reliable evidence about the relationship between menopausal age and the risk of long-term cardiometabolic disease.MethodsA comprehensive literature search of the PubMed, Web of Science, and Embase databases from inception to October 1, 2022, for titles and abstracts with a restriction to English language papers led to the discovery of the studies. Data are expressed as the Hazard Ratio (HR) with 95% confidence intervals (CI). The degree of heterogeneity was measured using the I-square (I2) index.Results921,517 participants from 20 cohort studies published between 1998 and 2022 were considered. Compared to women with menopause at age >45 years, women with premature menopause (PM) or early menopause (EM) had a higher risks of type 2 diabetes (RR: 1.32, 95% CI: 1.08–1.62; RR: 1.11, 95% CI: 0.91–1.36, respectively), hyperlipidemia (RR: 1.21, 95% CI: 1.05–1.39; RR: 1.17, 95% CI: 1.02–1.33, respectively), coronary heart disease (RR: 1.52, 95% CI: 1.22–1.91; RR: 1.19, 95% CI: 1.07–1.32, respectively), stroke (RR: 1.27, 95% CI: 1.02–1.58; RR: 1.13, 95% CI: 0.97–1.32, respectively) and total cardiovascular event (RR: 1.36, 95% CI: 1.16–1.60; RR: 1.14, 95% CI: 0.97–1.35, respectively). No difference was found for hypertension in PM or EM women (RR: 0.98, 95% CI: 0.89–1.07; RR: 0.97, 95% CI: 0.91–1.04, respectively). Additionally, we also found that PM women, but not EM women, were linked with an increased risk of ischemic and hemorrhagic stroke. However, this is not in line with the conclusion that both PM and EM had a higher risk of total stroke.ConclusionWomen with PM or EM have a higher risk of developing long-term CVD, compared to women with menopause at age >45 years. Therefore, we recommend early lifestyle interventions (e.g., maintaining a healthy lifestyle) and medical treatments (e.g., timely initiation of menopausal hormone therapy) to decrease the risk of cardiometabolic disease in early or premature menopausal women.Systematic Review RegistrationPROSPERO, identifier CRD42022378750

"心肾相交"作为中医学的重要理论,起源于《周易》,明清时期日趋完善.傅青主多从心肾立论,认为"心肾不交"是多种疾病的发病基础,故常用"交通心肾"法愈诸疾,而远志正是"交通心肾"的代表药.本文基于《傅青主医学全书》,结合"心肾相交"理论,探析傅青主运用远志特色,以期更好地传承傅青主学术思想,指导临床诊疗.

欧阳惠卿教授认为气血失和,脏腑功能失调,最终均可损伤冲任,导致各种类型的月经病.月经病临床常见的证型为冲任虚损型及冲任瘀滞型.欧阳惠卿教授治疗月经病注重调冲法,寓固冲于止血调经的始终,灵活辨用祛瘀法以理冲调经,同时常佐以清热法,以达冲任调及经复常的功效.固摄安冲可选安冲汤、固冲汤加减;祛瘀理冲在运用丹参、川芎、当归、赤芍等活血祛瘀药外,还常用三棱、莪术、鸡内金、水蛭等;清热祛瘀调冲可选生地黄与茜草等.