Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used in patients with chronic kidney disease (CKD), but existing evidence regarding their efficacy and safety remains inconsistent. To evaluate the cardiorenal outcomes and adverse effects of GLP-1 RAs in this population, we conducted a systematic review and meta-analysis of randomized controlled trials from PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science up to December 2024. Nine trials involving 21,717 patients, the vast majority of whom had T2DM, were included. GLP-1RAs treatment for CKD was associated with decreasing the incidence of major adverse kidney events (MAKE; RR, 0.84; 95% CI, 0.76-0.94) and major adverse cardiac and cerebrovascular events (MACE; RR, 0.84; 95% CI, 0.72-0.97), reducing all-cause mortality (RR, 0.83; 95% CI, 0.76-0.90) and albuminuria level (SMD, -1.22; 95% CI, -1.53 - 0.90). Gastrointestinal events associated with GLP-1 RA treatments including nausea (RR, 4.14; 95% CI, 2.70-6.33), vomiting (RR, 3.05; 95% CI, 1.88-4.97), diarrhea (RR, 2.65; 95% CI, 1.76-3.98), and dyspepsia (RR, 3.79; 95% CI, 1.02-14.12) have garnered significant attention. In conclusion, administration of GLP-1RAs treatment demonstrates excellent cardiorenal protective effects in CKD, primarily in patients with co-existing T2DM, though with notable gastrointestinal concerns.

INTRODUCTION:The bioactive components of Astragalus membranaceus and Salvia miltiorrhiza improved cardiac and renal function in chronic heart failure (CHF) and chronic kidney disease (CKD), respectively. However, the common regulating molecular mechanisms remain unclear. The aim of this study was to investigate these mechanisms using bioinformatics, network topology, and molecular dynamics simulation techniques. METHODS:The active components and target sites of A. membranaceus and S. miltiorrhiza were obtained from the Traditional Chinese Medicine Systems Pharmacology database. The targets of CKD and CHF were obtained from various databases for a protein-protein interaction analysis. The Gene Ontology (GO) function and Kyotoencyclopedia of genes and genomes (KEGG) pathway enrichment of intersection targets were analyzed by using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database. Molecular docking and dynamic simulations were conducted on the core ingredients and targets. The diagnostic efficiency of the key targets was evaluated by using receiver-operating characteristic (ROC) curves. RESULTS:A total of 70 active ingredients and 158 common targets were found. The top five core targets were AKT1, STAT3, TP53, MAPK1, and RELA. The GO enrichment analysis included apoptosis and oxidative stress. The KEGG pathway enrichment results indicated that the drug pair regulated the AGE-receptor for AGE signaling pathway, fluid shear stress and atherosclerosis, and the IL-17 signaling pathway. Molecular docking and dynamic simulations confirmed that the core ingredients had good affinity and stability with the key targets. The ROC curves confirmed the accuracy of every key target for identifying CKD and CHF and demonstrated that combining them improves diagnosis. CONCLUSION:The combination of A. membranaceus and S. miltiorrhiza proved effective for the treatment of CKD and CHF through various components, targets, and mechanisms. Moreover, it may predict the diagnostic value of key targets, providing a reference for clinical diagnostic applications.

Introduction Hypertensive nephropathy (HN) remains the second leading cause of end-stage renal disease. Tongxinluo capsule is commonly used in the treatment of HN under the condition that there is no specific therapy. We aimed to assess the efficacy and safety of Tongxinluo capsule for HN. Methods We systematically searched Pubmed, Embase, the Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journals Database of VIP INFORMATION, Wanfang Data, and SinoMed from their inception to December 2024. Randomized controlled trials (RCTs) comparing the efficacy of Tongxinluo capsule versus placebo or no specific therapy based on usual care among patients with hypertensive nephropathy were included. Study selection and data extraction were independently conducted by two reviewers. The primary outcome was 24-hour urine protein, and secondary outcomes include the level of urinary β2-microglobulin, creatinine clearance rate, serum creatinine, systolic blood pressure, and diastolic blood pressure. In terms of safety, the incidence of adverse events was the main indicator. A fixed-effects model or random-effects model was used when applicable. A 2-tailed p<0.05 was considered statistically significant. Results Eight RCTs (742 participants) were included in our study. The quantitative synthesis showed that Tongxinluo capsule could significantly reduce 24-hour proteinuria (MD, -0.11; 95 % CI, -0.20 to -0.02) and urinary β2-microglobulin (MD, -244.26; 95 % CI, -463.50 to -25.01), and slightly increase creatinine clearance rate (MD, 2.28; 95 % CI, 0.42 to 4.14). No significant differences were observed in decreasing serum creatinine (MD, -8.82; 95 % CI, -18.00 to 0.36), or antihypertensive effect (systolic blood pressure [MD, -2.18; 95 % CI, -5.98 to 1.63]; diastolic blood pressure [MD, -2.55; 95 % CI -6.03 to 0.92]). There are no obvious anomalies in terms of adverse events. Conclusion This is currently the first systematic review to provide up-to-date evidence regarding the Tongxinluo capsule treatment profile in HN. Based on the available RCTs, Tongxinluo capsule showed promising renal protective benefits in reducing proteinuria levels, and could be a therapeutic option for HN. High-quality studies are needed to further verify our findings. Protocol registration PROSPERO (CRD42023484654).

Mitophagy, the selective removal of damaged mitochondria, plays a critical role in kidney diseases, but its involvement in hypertensive nephropathy (HTN) is not well understood. To address this gap, we investigated mitophagy-related genes in HTN, identifying potential biomarkers for diagnosis and treatment. Transcriptome datasets from the Gene Expression Omnibus database were analyzed, resulting in the identification of seven mitophagy related differentially expressed genes (MR-DEGs), namely PINK1, ULK1, SQSTM1, ATG5, ATG12, MFN2, and UBA52. Further, we explored the correlation between MR-DEGs, immune cells, and inflammatory factors. The identified genes demonstrated a strong correlation with Mast cells, T-cells, TGFβ3, IL13, and CSF3. Machine learning techniques were employed to screen important genes, construct diagnostic models, and evaluate their accuracy. Consensus clustering divided the HTN patients into two mitophagy subgroups, with Subgroup 2 showing higher levels of immune cell infiltration and inflammatory factors. The functions of their proteins primarily involve complement, coagulation, lipids, and vascular smooth muscle contraction. Single-cell RNA sequencing revealed that mitophagy was most significant in proximal tubule cells (PTC) in HTN patients. Pseudotime analysis of PTC confirmed the expression changes observed in the transcriptome. Intercellular communication analysis suggested that mitophagy might regulate PTC's participation in intercellular crosstalk. Notably, specific transcription factors such as HNF4A, PPARA, and STAT3 showed strong correlations with mitophagy-related genes in PTC, indicating their potential role in modulating PTC function and influencing the onset and progression of HTN. This study offers a comprehensive analysis of mitophagy in HTN, enhancing our understanding of the pathogenesis, diagnosis, and treatment of HTN.

INTRODUCTION:Mycophenolate mofetil (MMF) is widely used off-label in patients with immunoglobulin A nephropathy (IgAN), although the literature does not consistently agree on its efficacy and safety. METHODS:We systematically searched PubMed, Embase, CENTRAL, CNKI, VIP, Wanfang Data, and SinoMed from their inception to August 2023. We included randomized controlled trials that enrolled patients of IgAN who received MMF treatment and compared effects with placebo or as an add-on therapy to usual care. Literature screening, risk of bias assessment, and data extraction were independently conducted in duplicate. Fixed-effects or random-effects meta-analyses were performed for pooling data where eligible. The primary outcomes were the composite kidney outcomes of major adverse kidney events (MAKDE) defined as doubling of serum creatinine, end-stage renal disease (ESRD), or death from a kidney disease-related or cardiovascular cause. RESULTS:Of 13 studies identified, 918 participants (463 [50.4%] treated with MMF) with IgAN were included in the analysis. MMF treatment in IgAN was associated with decreasing the occurrence of MAKDE (relative risk [RR], 0.32; 95% confidence interval [CI], 0.13-0.77), reducing proteinuria (RR, 1.41; 95% CI, 1.22-1.64), and lessening the probability of doubling blood creatinine (RR, 0.32, 95% CI, 0.14-0.72). No significant differences were detected in the incidence of ESRD (RR, 0.87, 95% CI, 0.38-2.03), or progression of chronic kidney disease (RR, 1.01; 95% CI, 0.22-4.57). Patients receiving MMF had a higher risk of infection (RR, 2.20; 95% CI, 1.21-4.00). CONCLUSION:MMF administration in IgAN indicates promising in decreasing the occurrence of MAKDE, reducing proteinuria level, and lessening the probability of doubling blood creatinine, but also comes with the risk of infection. These findings tend to be introduced to non-Caucasian population. The long-term favorable effects that MMF improved kidney outcomes still need further cross-regional and cross-ethnical verification.

IntroductionWith the increasing prevalence of hypertension, the incidence of kidney diseases is also increasing, resulting in a serious public burden. Jiangya Tongluo decoction (JYTL), a recognized prescription in traditional Chinese medicine (TCM), is commonly used to calm an overactive liver and reduce excess yang, while also promoting blood flow to alleviate obstructions in the meridians. Previous research has indicated that JYTL may help mitigate kidney damage caused by hypertension; however, the underlying mechanisms have not been thoroughly assessed.MethodsFirst, an amalgamation of UPLC-QE/MS and network pharmacology techniques was employed to pinpoint potential active components, primary targets, and crucial action mechanisms of JYTL in treating hypertensive nephropathy (HN). Then, we used spontaneous hypertensive rats (SHRs) and Wistar-Kyoto rats (WKYs) to evaluate the efficacy of JYTL on HN with valsartan as a positive reference. We also conducted DCFH-DA fluorescence staining in rat renal tissues to detect the level of ROS. Western blotting and immunohistochemistry were performed to investigate further the effect of JYTL decoction on key targets and signaling pathways.ResultsThrough UPLC-QE/MS and network analysis, 189 active ingredients and 5 hub targets were identified from JYTL. GSEA in the MitoCarta3.0 database and PPI network analysis revealed that JYTL predominantly engages in the Sirt1-mitophagy signaling pathway. Tanshinone iia, quercetin, and adenosine in JYTL are the main active ingredients for treating HN. In vivo validation showed that JYTL decoction could improve kidney function, ameliorate tubulointerstitial fibrosis (TIF), and improve mitochondrial function by inhibiting ROS production and regulating mitochondrial dynamics in SHRs. JYTL treatment could also increase the expression of SIRT1, PGC-1α, Nrf1, and TFAM, and activate PINK1/Parkin-mediated mitophagy.ConclusionJYTL decoction may exert renal function protective and anti-fibrosis effects in HN by ameliorating mitochondrial function and regulating the SIRT1/PGC-1α-mitophagy pathway.

本文探讨了腹诊在辨治荨麻疹中的理论内涵及临床应用.首先,从学术传承源流、学科发展与学派传承论述了腹诊的源流.其次,论述了腹诊用于辨治荨麻疹的机理在于腹部脏腑经络沟通将腹部脏器与体表连接成密切相关的整体.再次,论述了腹诊用于荨麻疹辨病因与病性、辨病位与病势的内容与方法.最后,介绍了腹诊在荨麻疹治疗中的临床应用,并举验案加以说明,突出阐明了腹诊在荨麻疹辨证治疗中的重要指导意义.

According to the theoretical basis of deficiency and stasis in traditional Chinese medicine, Professor Zhang Daning proposes the pathogenesis of diabetic kidney disease（DKD）from the theory of kidney deficiency and blood stasis and develops the therapy of tonifying kidney and activating blood.In clinical practice, the DKD patients mainly present the syndrome of kidney deficiency and blood stasis, which is complicated with dampness turbidity or dampness toxin sometimes.Accordingly, tonifying kidney and activating blood is the fundamental therapy, which can be supplemented with the therapy of invigorating spleen and expelling dampness.The therapy of invigorating spleen and replenishing kidney is essential, and importance should be attached to activating blood and resolving stasis throughout the whole treatment process.Treatment by stages should be employed according to the etiology and pathogenesis, and prescriptions should be modified according to the characteristics of disease procession.

慢性肾脏病的病性是本虚标实,虚实夹杂,其中脾肾阳气亏虚为本,风邪、湿浊、瘀血为标,虚实夹杂既有因虚致实,又有因实致虚,两者相互影响,以致恶性循环.阳气在人体内起着温煦、卫外、推动、固摄、气化的重要作用,故历代医家常常重视阳气,逐步形成"重阳思想"理论."重阳思想"理论源于《黄帝内经》,继承发展于张仲景、张景岳,推崇升华于郑钦安、祝味菊,是中医认识疾病、治疗疾病的重要思想理论之一,其核心内涵是强调阳气对生命活动和机体健康的主导作用.基于"重阳思想"理论,结合慢性肾脏病脾肾阳虚、湿浊瘀阻之病机关键,治以扶阳法为主,以固护人体之根本,包括温补阳气、顾护阳气、通达阳气,即临床上重视温补脾肾阳气固其本,祛风散邪固表、利水渗湿化浊、活血化瘀通络治其标,以顾护被损之阳气,通达被遏之阳气,恢复肾之开阖气化之机能,取得了较好临床效果.本文通过阐述"重阳思想"理论在治疗慢性肾脏病的应用体会,以供同道所参考.

慢性肾衰竭( chronic renal failure,CRF)是各种肾脏疾病发展到最后阶段的临床综合征,以体内代谢产物蓄积,水、电解质及酸碱平衡失调以及全身多系统受累为主要表现.该病起病隐匿,病因复杂,临床常见恶心呕吐、腰痛、乏力、尿少、浮肿、皮肤瘙痒、贫血等症,据此本病可归属于中医虚劳、关格、癃闭、肾风等范畴.中医药在治疗CRF方面积累了丰富的临床经验,同时对延缓CRF进展有确切的疗效及特色[1].

"水郁折之"理论出自《黄帝内经》.肾在五行属水,因此水郁也可理解为肾郁,包括肾功能之郁和结构之郁两个方面.前者指肾中阴阳气血阻滞不通,导致功能受损;后者为玄府-肾络微观结构被有形之邪郁遏,二者相互影响,共同导致水饮、瘀血、痰浊等病理产物积聚,进一步加重"水郁",形成恶性循环."水郁折之"中的"折"有通的含义,具体治法包括通肾阳、通玄府、通肾络,即运用辛温宣散、化气利水法解决功能之郁;以升散通透、以清换浊法开玄府,濡润通补、化瘀通络法疏通肾络,解决结构之郁.诸法配合,随证治之,恢复肾主水、司开阖、主封藏等功能,则津液四布,精不外溢,气血通畅,肾性水肿自除.

传统卫气营血辨证将温病分为卫分证、气分证、营分证、血分证四个阶段,强调根据疾病的不同阶段进行治疗.本文通过阐述卫气同治理论,指出卫分证与气分证病机均属郁热在里,且温热之邪传变迅速,二者并无明确界限,因此温病初起常表现为卫气同病.治疗则不必拘泥于传统卫气营血序贯疗法而应用卫气同治理论,即在温病初起即采用辛散疏卫与清解气分合用的治疗方法,一方面应用辛散之品宣发郁热,透邪外出;另一方面要重视气分,疏卫同时配伍清气之品,截断病程进展.卫气同治理论指导温病诊疗具有药效力专,避免失治、误治;截断病程进展,未病先防;在外感热病治疗中贡献突出等优势.该理论包括火郁发之、分消走泄、抑邪扶正三个方面.

作为《金匮要略》五种水气病之一,黄汗病症状表现复杂多样,病机虚实兼见,并涉及多个脏腑.种种原因,导致其理论内涵尚未得到充分的阐发.系统性红斑狼疮是现代医学累及多系统的难治性疾病.其临床表现,发展转归与黄汗病具有极高的契合度,将系统性红斑狼疮归入黄汗病范畴具有合理性.素有肝肾亏虚、阳明热盛,又因调摄不慎,外感寒湿之邪,是系统性红斑狼疮的关键病机.基于《伤寒杂病论》黄汗病以及其余相关理论,针对系统性红斑狼疮肾脏、皮肤黏膜、骨骼肌肉、消化、呼吸、心脏、神经等系统受累所表现出的各种临床表现,以补益肝肾、清解阳明、散寒除湿为原则,分别提出了相应的经方治疗,为系统性红斑狼疮的现代中医诊治提供了思路.

北京郭氏医学流派是以名老中医郭士魁先生、郭维琴教授及郭志强教授两代名老中医及其第三代传承人形成的医学流派,对治疗更年期高血压有独到的经验.更年期高血压是一种涉及生殖内分泌、心血管等多系统的身心疾病.郭氏医学认为更年期高血压的核心病机是阴虚阳亢,基本病机是妇人多郁、阴血常虚,重要病机是血瘀络阻,治疗当滋补肝肾、平肝潜阳、柔肝解郁、化瘀通络,具有较好的临床疗效.

Purpose: In this study, we investigated the mechanism of Tongluo Yishen (TLYS) decoction in more detail, from the perspective of pyroptosis in the unilateral ureteral ligation (UUO) model and the hypoxia-induced renal tubular epithelial (NRK-52E) cell. Method: The UUO model was used, and after 14 days of TLYS intervention, rats were tested for blood creatinine and urea nitrogen, HE staining was used to observe the pathological changes in the kidney, Masson staining was used to assess the degree of interstitial fibrosis, western blot was used to detect the changes of α-smooth muscle actin (α-SMA) protein expression level, immunohistochemistry and western blot detected the changes in protein expression levels of NOD-like receptor protein 3 inflammasome (NLRP3), gasdermin D (GSDMD), cysteinyl aspartate specific proteinase (caspase-1), interleukin 18 (IL-18) and interleukin 1β (I L-1β). A hypoxia model was created using NRK-52E cell, and after different concentrations of TLYS decoction intervention, the changes in the expression levels of pyroptosis were used with immunofluorescence and western blot methods. Results: TLYS decoction improved renal function, delayed the advancement of renal interstitial fibrosis, and inhibited pyroptosis in UUO rats. Furthermore, we observed that TLYS can mitigate hypoxia-induced NRK-52E cell damage via the suppression of the NLRP3-mediated pyroptosis. Conclusion: TLYS decoction exert renoprotective effects by inhibiting NLRP3-mediated pyroptosis.

目的:对雷公藤制剂治疗过敏性紫癫肾炎的有效性和安全性进行meta分析.方法:检索PubMed、EMBASE、The Cochrane Library、CNKI、VIP、WangFang Data和CBM数据库,收集雷公藤制剂治疗过敏性紫癫肾炎的干预性研究,由2名研究者独立筛选文献、提取资料,采用Revman5.3软件进行meta分析.结果:纳入33篇文献,研究对象共计2712例,文献偏倚风险评价质量均较低:meta分析结果显示:试验组临床有效率优于对照组(P<0.01),试验组改善蛋白尿(P<0.01),尿红细胞(P<0.01),血IgA(P<0.01)均优于对照组,试验组肝功能损伤(P<0.01)和白细胞减少(P<0.01)均多于对照组,在儿童中尤为明显.结论:雷公藤制剂能改善HSPN蛋白尿和血尿,降低血IgA,但存在肝功能损伤和血白细胞减少的副作用,尤其是在HSPN儿童中,临床实践中因注意使用剂量和时间,并定期监测和及时处理相关不良反应.

治未病的概念包含未病先防、防微杜渐、防止传变、病后防复等几项,如今文献对防微杜渐等单独论述较少.因此阅读分析《黄帝内经》原文,对"微病"的防治等概念加以探讨.通过对《黄帝内经》原文的整理得知,微病邪微正瑕,病位浅且病势轻,且症状不显容易被忽略,但可转为重病,需要高超的医技方可识别.以五脏为基础,可以把微病分为"神之微""白气微泄""留血""微风""骨节动"五类,各发病于毫毛、皮肤腠理、络脉、肌肉、骨节等部位,其表现为体表感觉异常、皮腠不适微汗、瘀血、肌肉骨节异动等.在治疗时针对五脏特点和病位,以调畅气血、通络驱邪为原则,使用药食调养、针刺、导引按摩、情志疏导等方法配合使用进行调理,从而使人体气血通达,经络通畅,五脏安定,微病向愈,不再为患.

慢性肾脏病( chronic kidney disease,CKD)是指3个月及以上对健康产生影响的肾脏结构或功能异常.随着糖尿病、高血压和肥胖等病发病率增高,以及人口老龄化等原因,慢性肾脏病的发病率逐年升高,且已经成为全球性的公共卫生问题[1].其发病具有"三高三低"的特点,即高患病率、高死亡率、高心血管疾病伴发率、低知晓率、低防治率、低伴发心血管疾病知晓率.2015年一项全球性的疾病分析显示全球范围内CKD患者约有3. 2亿例[2] ,在我国,CKD的患病率约为10. 8％ [3].

目的:探讨通络益肾方对单侧输尿管结扎大鼠肾间质纤维化及肾上腺髓质素(ADM)表达的影响,并探究其可能的机制.方法:将50只雄性SD大鼠按随机数字表法分为5组:假手术组、模型组、通络益肾方组、缬沙坦组、ADM观察组,每组10只.分别采取相应的干预措施.Masson染色观察大鼠肾脏的病理改变;免疫组织化学法检测大鼠肾脏E-钙黏蛋白(E-cadherin)的表达;放射免疫法检测大鼠血清ADM水平;ELISA检测大鼠血清Ⅲ型前胶原(PCⅢ)、肾组织ADM水平,并对肾组织ADM和E-cadherin进行相关性分析.结果:与假手术组比较,模型组血清ADM、PCⅢ水平明显升高(P<0.01),肾组织E-cadherin、ADM水平降低(P<0.01).与模型组比较,通络益肾方组和缬沙坦组血清ADM、PCⅢ水平降低(P<0.01、P<0.05),肾组织E-cadherin、ADM水平升高(P<0.01、P<0.05);ADM观察组血清PCⅢ水平降低(P<0.05),血清ADM、肾组织E-cadherin、ADM水平升高(P<0.05).其中肾组织ADM与E-cadherin水平呈显著正相关(r=0.62,P<0.01).结论:通络益肾方能够改善肾间质纤维化模型(UUO)大鼠肾间质纤维化,抑制纤维化指标PCⅢ的表达,上调E-cadherin的表达,其作用机制可能是通过上调肾脏局部ADM蛋白表达而实现的.