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Clinical features and genetic analysis of 15 Chinese children with dent disease. 15 名中国儿童牙病患者的临床特征和基因分析。
IF 3 3区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-12-01 Epub Date: 2024-05-10 DOI: 10.1080/0886022X.2024.2349133
Qian Li, Zhenle Yang, Ruixian Zang, Suwen Liu, Lichun Yu, Jing Wang, Cong Wang, Xiaoyuan Wang, Shuzhen Sun

Objective:  The clinical characteristics, genetic mutation spectrum, treatment strategies and prognoses of 15 children with Dent disease were retrospectively analyzed to improve pediatricians' awareness of and attention to this disease.

Methods:  We analyzed the clinical and laboratory data of 15 Chinese children with Dent disease who were diagnosed and treated at our hospital between January 2017 and May 2023 and evaluated the expression of the CLCN5 and OCRL1 genes.

Results:  All 15 patients were male and complained of proteinuria, and the incidence of low-molecular-weight proteinuria (LMWP) was 100.0% in both Dent disease 1 (DD1) and Dent disease 2 (DD2) patients. The incidence of hypercalciuria was 58.3% (7/12) and 66.7% (2/3) in DD1 and DD2 patients, respectively. Nephrocalcinosis and nephrolithiasis were found in 16.7% (2/12) and 8.3% (1/12) of DD1 patients, respectively. Renal biopsy revealed focal segmental glomerulosclerosis (FSGS) in 1 patient, minimal change lesion in 5 patients, and small focal acute tubular injury in 1 patient. A total of 11 mutations in the CLCN5 gene were detected, including 3 missense mutations (25.0%, c.1756C > T, c.1166T > G, and c.1618G > A), 5 frameshift mutations (41.7%, c.407delT, c.1702_c.1703insC, c.137delC, c.665_666delGGinsC, and c.2200delG), and 3 nonsense mutations (25.0%, c.776G > A, c.1609C > T, and c.1152G > A). There was no significant difference in age or clinical phenotype among patients with different mutation types (p > 0.05). All three mutations in the OCRL1 gene were missense mutations (c.1477C > T, c.952C > T, and c.198A > G).

Conclusion:  Pediatric Dent disease is often misdiagnosed. Protein electrophoresis and genetic testing can help to provide an early and correct diagnosis.

目的 回顾性分析15例Dent病患儿的临床特征、基因突变谱、治疗策略和预后,以提高儿科医生对该病的认识和重视: 我们分析了2017年1月至2023年5月期间在我院诊治的15名中国登特病患儿的临床和实验室数据,并评估了CLCN5和OCRL1基因的表达: 15名患者均为男性,主诉蛋白尿,其中登特病1(DD1)和登特病2(DD2)患者低分子量蛋白尿(LMWP)发生率均为100.0%。在 DD1 和 DD2 患者中,高钙尿症的发生率分别为 58.3%(7/12)和 66.7%(2/3)。DD1患者中分别有16.7%(2/12)和8.3%(1/12)的人出现肾癌和肾结石。肾活检显示,1 名患者出现局灶节段性肾小球硬化(FSGS),5 名患者出现微小病变,1 名患者出现小灶性急性肾小管损伤。CLCN5基因共检测到11个突变,包括3个错义突变(25.0%,c.1756C > T、c.1166T > G和c.1618G > A)、5个框移突变(41.7%,c.407delT、c.1702_c.1703insC、c.137delC、c.665_666delGGinsC 和 c.2200delG),以及 3 个无义突变(25.0%,c.776G > A、c.1609C > T 和 c.1152G > A)。不同突变类型的患者在年龄和临床表型上没有明显差异(P > 0.05)。OCRL1基因的三个突变均为错义突变(c.1477C > T、c.952C > T和c.198A > G): 结论:小儿牙病经常被误诊。结论:小儿牙病经常被误诊,蛋白质电泳和基因检测有助于提供早期和正确的诊断。
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引用次数: 0
Exploring therapeutic mechanisms of Chuan Huang Fang-II in the treatment of acute kidney injury on chronic kidney disease patients from the perspective of lipidomics. 从血脂组学角度探讨川黄连Ⅱ号治疗慢性肾脏病急性肾损伤的机制
IF 3 3区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-12-01 Epub Date: 2024-05-24 DOI: 10.1080/0886022X.2024.2356021
Ling Chen, Qian Wang, Tonglu Li, Lejia Li, Chen Wang, Bing Xu, Xuezhong Gong

Objective: This study aims to assess the clinical efficacy and safety of CHF-II in combination with RG for treating AKI on CKD (A on C), and to explore potential therapeutic mechanisms through lipidomics analysis.

Methods: 98 patients were enrolled and randomly assigned to the RG or RG + CHF groups. Both groups received RG therapy, with RG + CHF group additionally receiving CHF-II treatment over a duration of two weeks. Evaluation endpoints included changes in renal function, blood lipid profiles, urinary AKI biomarkers, and TCM symptoms before and after treatment. Serum samples were collected for lipid metabolite analysis.

Results: The total clinical effective rate in RG + CHF group was 73.5%, and that of RG group was 40.8%. TCM syndrome scores in RG + CHF group showed a more pronounced decrease (p < 0.05). Scr, BUN, and UA levels decreased while eGFR levels increased in both groups (p < 0.05), with a greater magnitude of change observed in the RG + CHF group. Urinary AKI biomarkers decreased more in RG + CHF group (p < 0.05). No serious adverse events occurred during the trial. 58 different lipid metabolites and 48 lipid biomarkers were identified. According to the KEGG database, the possible metabolic pathways involved triglyceride metabolic pathway and fat digestion and absorption metabolic pathways.

Conclusion: CHF-II effectively alleviated kidney injury and improved TCM syndrome scores in patients with A on C. Lipid differential metabolites could serve as diagnostic indicators for AKI in patients with CKD. The possible metabolic pathways might be implicated in therapeutic action of CHF-II in the prevention and treatment of patients with A on C.

研究目的本研究旨在评估 CHF-II 联合 RG 治疗 CKD(A on C)AKI 的临床疗效和安全性,并通过脂质组学分析探讨潜在的治疗机制。两组患者均接受 RG 治疗,RG + CHF 组还接受为期两周的 CHF-II 治疗。评估终点包括治疗前后肾功能、血脂、尿AKI生物标志物和中医症状的变化。采集血清样本用于脂质代谢物分析:结果:RG + CHF 组临床总有效率为 73.5%,RG 组为 40.8%。RG+CHF组的中医综合征评分下降更明显(P P P 结论:RG+CHF组的中医综合征评分下降更明显,RG+CHF组的中医综合征评分下降更明显:CHF-II能有效缓解肾损伤,并改善丙型肝炎患者的中医综合征评分。脂质差异代谢物可作为诊断CKD患者AKI的指标。CHF-II在预防和治疗丙型肝炎合并甲型肝炎患者的治疗作用中可能涉及的代谢途径。
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引用次数: 0
Increased indexed proximal aortic diameter is a predictor of poor prognosis in maintenance hemodialysis patients. 指数化近端主动脉直径增大是维持性血液透析患者预后不良的预测因素。
IF 3 3区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-12-01 Epub Date: 2024-05-24 DOI: 10.1080/0886022X.2024.2355352
Junwei Xu, Wenyi Tang, Lizheng Song, Yuxi Huang, Li Xiao, Fangyuan Cheng, Qianglin Guan, Mei Xu, Chuoxin Ma, Jian Chen, Jianting Ke

Background: Recent studies have shown that the baseline values of absolute aortic root diameter (ARD) and indexed diameter are associated with all-cause mortality and cardiovascular events in the general population, even in the absence of aneurysmal aortic disease. However, there is limited available data on the association between ARD and prognosis in end-stage renal disease (ESRD) patients receiving maintenance hemodialysis (MHD). Accordingly, the purpose of this study is to investigate the predictive value of ARD for all-cause mortality and cardiovascular events in this specific population.Methods: ARD was measured by echocardiography at the level of the sinuses of Valsalva at end diastole and indexed to body surface area (BSA). The primary endpoint was all-cause mortality. The secondary endpoint was major adverse cardiovascular events (MACE), including cardiovascular mortality, myocardial infarction and stroke. Cox proportional hazards models were conducted to evaluate the association between baseline ARD/BSA and clinical outcomes.Results: A total of 391 patients were included in this study. The primary endpoint occurred in 95 (24.3%) patients while the secondary endpoint occurred in 71 (18.2%) patients. Multivariate Cox regression analysis showed that ARD/BSA was an independent prognostic factor for all-cause mortality (HR, per 1-SD increase, 1.403; 95% CI, 1.118-1.761; p = 0.003) as well as MACE (HR, per 1-SD increase, 1.356; 95% CI, 1.037-1.772; p = 0.026).Conclusions: Our results show that ARD/BSA is predictive of all-cause mortality and MACE in MHD patients with ESRD and support the view that assessment of ARD/BSA may refine risk stratification and preventive strategies in this population.

背景:最近的研究表明,在普通人群中,即使没有动脉瘤性主动脉疾病,主动脉根部绝对直径(ARD)和指数直径的基线值也与全因死亡率和心血管事件有关。然而,关于接受维持性血液透析(MHD)的终末期肾病(ESRD)患者的 ARD 与预后之间关系的现有数据非常有限。因此,本研究旨在调查 ARD 对这一特殊人群的全因死亡率和心血管事件的预测价值:通过超声心动图测量舒张末期瓦尔萨尔瓦窦水平的 ARD,并与体表面积(BSA)进行指数化。主要终点是全因死亡率。次要终点是主要心血管不良事件(MACE),包括心血管死亡率、心肌梗死和中风。采用 Cox 比例危险模型评估基线 ARD/BSA 与临床结果之间的关系:本研究共纳入了 391 名患者。95名患者(24.3%)达到了主要终点,71名患者(18.2%)达到了次要终点。多变量 Cox 回归分析显示,ARD/BSA 是全因死亡率(HR,每增加 1-SD,1.403;95% CI,1.118-1.761;p = 0.003)和 MACE(HR,每增加 1-SD,1.356;95% CI,1.037-1.772;p = 0.026)的独立预后因素:我们的研究结果表明,ARD/BSA 可预测患有 ESRD 的 MHD 患者的全因死亡率和 MACE,并支持这样的观点,即评估 ARD/BSA 可完善该人群的风险分层和预防策略。
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引用次数: 0
Risk factors for cardio-cerebrovascular events among patients undergoing continuous ambulatory peritoneal dialysis and their association with serum magnesium. 持续非卧床腹膜透析患者发生心脑血管事件的风险因素及其与血清镁的关系。
IF 3 3区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-12-01 Epub Date: 2024-05-24 DOI: 10.1080/0886022X.2024.2355354
Penglei Li, Tiegang Lv, Liping Xu, Wenlu Yu, Yuanyuan Lu, Yuanyuan Li, Jian Hao

Serum magnesium levels exceeding 0.9 mmol/L are associated with increased survival rates in patients with CKD. This retrospective study aimed to identify risk factors for cardio-cerebrovascular events among patients receiving continuous ambulatory peritoneal dialysis (CAPD) and to examine their correlations with serum magnesium levels. Sociodemographic data, clinical physiological and biochemical indexes, and cardio-cerebrovascular event data were collected from 189 patients undergoing CAPD. Risk factors associated with cardio-cerebrovascular events were identified by univariate binary logistic regression analysis. Correlations between the risk factors and serum magnesium levels were determined by correlation analysis. Univariate regression analysis identified age, C-reactive protein (CRP), red cell volume distribution width standard deviation, red cell volume distribution width corpuscular volume, serum albumin, serum potassium, serum sodium, serum chlorine, serum magnesium, and serum uric acid as risk factors for cardio-cerebrovascular events. Among them, serum magnesium ≤0.8 mmol/L had the highest odds ratio (3.996). Multivariate regression analysis revealed that serum magnesium was an independent risk factor, while serum UA (<440 μmol/L) was an independent protective factor for cardio-cerebrovascular events. The incidence of cardio-cerebrovascular events differed significantly among patients with different grades of serum magnesium (χ2 = 12.023, p = 0.002), with the highest incidence observed in patients with a serum magnesium concentration <0.8 mmol/L. High serum magnesium levels were correlated with high levels of serum albumin (r = 0.399, p < 0.001), serum potassium (r = 0.423, p < 0.001), and serum uric acid (r = 0.411, p < 0.001), and low levels of CRP (r = -0.279, p < 0.001). In conclusion, low serum magnesium may predict cardio-cerebrovascular events in patients receiving CAPD.

血清镁水平超过 0.9 mmol/L 与慢性肾脏病患者生存率的提高有关。这项回顾性研究旨在确定接受连续不卧床腹膜透析(CAPD)患者发生心脑血管事件的风险因素,并研究这些因素与血清镁水平的相关性。研究收集了 189 名接受 CAPD 患者的社会人口学数据、临床生理生化指标以及心脑血管事件数据。通过单变量二元逻辑回归分析确定了与心脑血管事件相关的风险因素。通过相关性分析确定了风险因素与血清镁水平之间的相关性。单变量回归分析确定了年龄、C 反应蛋白(CRP)、红细胞体积分布宽度标准差、红细胞体积分布宽度血球容积、血清白蛋白、血清钾、血清钠、血清氯、血清镁和血清尿酸为心脑血管事件的危险因素。其中,血清镁≤0.8 mmol/L的几率比最高(3.996)。多变量回归分析显示,血清镁是一个独立的风险因素,而血清 UA(χ2 = 12.023,P = 0.002),在血清镁浓度为 r = 0.399、p r = 0.423、p r = 0.411、p p 0.001 的患者中观察到的发病率最高。)总之,低血清镁可预测接受 CAPD 患者的心脑血管事件。
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引用次数: 0
Prognosis and factors related to severe secondary hyperparathyroidism in long-term peritoneal dialysis patients. 长期腹膜透析患者严重继发性甲状旁腺功能亢进症的预后和相关因素
IF 3 3区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-12-01 Epub Date: 2024-05-27 DOI: 10.1080/0886022X.2024.2356022
Yanmei Li, Xiaonan Feng, Na Chen, Shuhua Song, Min Yu, Yan Wang, Hongxia Zhang, Li Wang, Menghua Chen, Na Tian

Secondary hyperparathyroidism (SHPT) can progress to severe SHPT (sSHPT), which affects the survival rate and quality of life of patients. This retrospective cohort study investigated risk factors for sSHPT and the association between SHPT and mortality (all-cause and infection-related) among 771 clinically stable patients (421 male patients; mean age, 51.2 years; median dialysis vintage, 28.3 months) who underwent >3 months of regular peritoneal dialysis (PD) between January 2013 and March 2021. The sSHPT and non-sSHPT groups comprised 75 (9.7%) (median progression, 35 months) and 696 patients, respectively. sSHPT was defined as a serum intact parathyroid hormone (PTH) level >800 pg/mL observed three times after active vitamin D pulse therapy. The influence of sSHPT on the prognosis of and risk factors for sSHPT progression were evaluated using logistic and Cox regression analyses. After adjusting for confounding factors, higher (each 100-pg/mL increase) baseline PTH levels (95% confidence interval (CI) 1.206-1.649, p < .001), longer (each 1-year increase) dialysis vintages (95% CI 1.013-1.060, p = .002), higher concomitant diabetes rates (95% CI 1.375-10.374, p = .010), and lower (each 1-absolute unit decrease) Kt/V values (95% CI 0.859-0.984, p = .015) were independent risk factors for progression to sSHPT in patients on PD. During follow-up, 211 deaths occurred (sSHPT group, n = 35; non-sSHPT group, n = 176). The sSHPT group had significantly higher infection-related mortality rates than the non-sSHPT group (12.0% vs. 4.3%; p < .05), and sSHPT was associated with increased infection-related mortality. In conclusion, patients with sSHPT are at higher risk for death and infection-related mortality than patients without sSHPT.

继发性甲状旁腺功能亢进症(SHPT)可发展为重度甲状旁腺功能亢进症(sSHPT),从而影响患者的生存率和生活质量。这项回顾性队列研究调查了 2013 年 1 月至 2021 年 3 月期间接受定期腹膜透析(PD)超过 3 个月的 771 名临床病情稳定的患者(421 名男性患者;平均年龄 51.2 岁;中位透析年限 28.3 个月)中出现 sSHPT 的风险因素以及 SHPT 与死亡率(全因和感染相关)之间的关系。sSHPT组和非sSHPT组分别包括75名(9.7%)(中位进展期为35个月)和696名患者。sSHPT的定义是在积极的维生素D脉冲疗法后观察到三次血清完整甲状旁腺激素(PTH)水平>800 pg/mL。采用逻辑和 Cox 回归分析评估了 sSHPT 对 sSHPT 预后的影响和 sSHPT 进展的风险因素。在对混杂因素进行调整后,较高的(每增加 100-pg/mL )基线 PTH 水平(95% 置信区间 (CI) 1.206-1.649,p = .002)、较高的并发糖尿病率(95% CI 1.375-10.374,p = .010)和较低的(每降低 1 个绝对单位)Kt/V 值(95% CI 0.859-0.984,p = .015)是 PD 患者进展为 sSHPT 的独立风险因素。随访期间,共有 211 人死亡(sSHPT 组,n = 35;非 sSHPT 组,n = 176)。sSHPT 组的感染相关死亡率明显高于非 sSHPT 组(12.0% vs. 4.3%; p
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引用次数: 0
Medication burden in patients with dialysis-dependent CKD: a systematic review. 透析依赖型慢性肾脏病患者的用药负担:系统综述。
IF 3 3区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-12-01 Epub Date: 2024-06-04 DOI: 10.1080/0886022X.2024.2353341
Xuemei Liu, Ping Chen, Yun Liu, Xiaoyan Jia, Dongmei Xu

This systematic review aimed to statistically profile the medication burden and associated influencing factors, and outcomes in patients with dialysis-dependent chronic kidney disease (DD-CKD). Studies of medication burden in patients with DD-CKD in the last 10 years from 1 January 2013 to 31 March 2024 were searched from PubMed, Embase, and Cochrane databases. Newcastle-Ottawa Scale (NOS) or Agency for Healthcare Research and Quality (AHRQ) methodology checklist was used to evaluate quality and bias. Data extraction and combining from multiple groups of number (n), mean, and standard deviation (SD) were performed using R programming language (version4.3.1; R Core Team, Vienna, Austria). A total of 10 studies were included, and the results showed a higher drug burden in patients with DD-CKD. The combined pill burden was 14.57 ± 7.56 per day in hemodialysis (HD) patients and 14.63 ± 6.32 in peritoneal dialysis (PD) patients. The combined number of medications was 9.74 ± 3.37 in HD and 8 ± 3 in PD. Four studies described the various drug classes and their proportions, in general, antihypertensives and phosphate binders were the most commonly used drugs. Five studies mentioned factors associated with medication burden. A total of five studies mentioned medication burden-related outcomes, with one study finding that medication-related burden was associated with increased treatment burden, three studies finding that poor medication adherence was associated with medication burden, and another study finding that medication complexity was not associated with self-reported medication adherence. Limitations: meta-analysis was not possible due to the heterogeneity of studies.

本系统性综述旨在统计透析依赖型慢性肾病(DD-CKD)患者的用药负担、相关影响因素和治疗效果。研究人员在 PubMed、Embase 和 Cochrane 数据库中检索了 2013 年 1 月 1 日至 2024 年 3 月 31 日这 10 年间有关 DD-CKD 患者用药负担的研究。采用纽卡斯尔-渥太华量表(NOS)或美国医疗保健研究与质量机构(AHRQ)方法检查表来评估质量和偏倚。使用 R 编程语言(版本 4.3.1;R 核心小组,奥地利维也纳)进行数据提取并合并多组数字(n)、平均值和标准差(SD)。共纳入了 10 项研究,结果显示 DD-CKD 患者的药物负担较重。血液透析(HD)患者每天的综合药物负担为(14.57 ± 7.56)粒,腹膜透析(PD)患者为(14.63 ± 6.32)粒。血液透析(HD)和腹膜透析(PD)患者的合计药物数量分别为(9.74 ± 3.37)和(8 ± 3)。四项研究描述了各种药物类别及其比例,总的来说,降压药和磷酸盐结合剂是最常用的药物。五项研究提到了与用药负担相关的因素。共有五项研究提到了与用药负担相关的结果,其中一项研究发现与用药相关的负担与治疗负担的增加有关,三项研究发现用药依从性差与用药负担有关,另一项研究发现用药复杂性与自我报告的用药依从性无关。局限性:由于研究的异质性,无法进行荟萃分析。
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引用次数: 0
Identification of a novel nonsense mutation in α-galactosidase A that causes Fabry disease in a Chinese family. 在一个中国家庭中鉴定出一种导致法布里病的α-半乳糖苷酶A新型无义突变。
IF 3 3区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-12-01 Epub Date: 2024-06-07 DOI: 10.1080/0886022X.2024.2362391
Yushi Peng, Meize Pan, Yuchen Wang, Zongrui Shen, Jian Xu, Fu Xiong, Hongbo Xiao, Yun Miao

Fabry disease, a lysosomal storage disease, is an uncommon X-linked recessive genetic disorder stemming from abnormalities in the alpha-galactosidase gene (GLA) that codes human alpha-Galactosidase A (α-Gal A). To date, over 800 GLA mutations have been found to cause Fabry disease (FD). Continued enhancement of the GLA mutation spectrum will contribute to a deeper recognition and underlying mechanisms of FD. In this study, a 27-year-old male proband exhibited a typical phenotype of Fabry disease. Subsequently, family screening for Fabry disease was conducted, and high-throughput sequencing was employed to identify the mutated gene. The three-level structure of the mutated protein was analyzed, and its subcellular localization and enzymatic activity were determined. Apoptosis was assessed in GLA mutant cell lines to confirm the functional effects. As a result, a new mutation, c.777_778del (p. Gly261Leufs*3), in the GLA gene was identified. The mutation caused a frameshift during translation and the premature appearance of a termination codon, which led to a partial deletion of the domain in C-terminal region and altered the protein's tertiary structure. In vitro experiments revealed a significant reduction of the enzymatic activity in mutant cells. The expression was noticeably decreased at the mRNA and protein levels in mutant cell lines. Additionally, the subcellular localization of α-Gal A changed from a homogeneous distribution to punctate aggregation in the cytoplasm. GLA mutant cells exhibited significantly higher levels of apoptosis compared to wild-type cells.

法布里病是一种溶酶体贮积病,是一种不常见的 X 连锁隐性遗传疾病,源于编码人类α-半乳糖苷酶 A(α-Gal A)的α-半乳糖苷酶基因(GLA)异常。迄今为止,已发现 800 多种 GLA 基因突变可导致法布里病(FD)。不断扩大 GLA 基因突变谱将有助于更深入地认识法布里病及其潜在机制。在本研究中,一名 27 岁的男性原患者表现出典型的法布里病表型。随后,进行了法布里病家族筛查,并采用高通量测序鉴定了突变基因。对突变蛋白的三级结构进行了分析,并确定了其亚细胞定位和酶活性。评估了GLA突变细胞系的凋亡情况,以确认其功能效应。结果,在 GLA 基因中发现了一个新的突变,即 c.777_778del (p. Gly261Leufs*3)。该突变导致翻译过程中的框架偏移和终止密码子的过早出现,从而导致 C 端区域结构域的部分缺失,并改变了蛋白质的三级结构。体外实验显示,突变体细胞的酶活性显著降低。突变体细胞系的 mRNA 和蛋白质水平的表达量明显下降。此外,α-Gal A 的亚细胞定位从均匀分布变为细胞质中的点状聚集。与野生型细胞相比,GLA突变型细胞的凋亡水平明显更高。
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引用次数: 0
An extra honey polyphenols-rich diet ameliorates the high-fat diet induced chronic kidney disease via modulating gut microbiota in C57BL/6 mice. 富含额外蜂蜜多酚的饮食可通过调节 C57BL/6 小鼠的肠道微生物群来改善高脂饮食诱发的慢性肾病。
IF 3 3区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-12-01 Epub Date: 2024-06-28 DOI: 10.1080/0886022X.2024.2367700
Xirong Cao, Fangrui Xu, Haoan Zhao, Jingyao Zhang, Chang Liu

Honey is not equivalent to sugar and possess a worldwide health promoting effects such as antioxidant, antibacterial, anti-inflammatory, and hepatoprotective activities. Nevertheless, the potential impacts of honey on high-fat diet induced chronic kidney disease (CKD) and gut microbiota remain to be explored. Herein a high-fat diet was used to induce a mouse CKD model, and analysis was conducted on liver, kidney, spleen indices, tissue morphology, biochemical parameters, CKD related genes, and gut microbial diversity. The results indicated that significant inhibitory effects on renal damage caused by a high-fat diet in mice and improvement in disease symptoms were observed upon honey treatment. Significant changes were also found in serum TC, TG, UA, and BUN as well as the inflammation-related protein TNF-α and IL-6 levels in renal tissues. Gene expression analysis revealed that honey intake closely relates to gut microbiota diversity, which can regulate the composition of gut microbiota, increase microbial diversity, especially Bifidobacteriales and S24_7 and promote the synthesis of short chain fatty acids (SCFAs). In summary, this study suggests that honey has both preventive and therapeutic effects on CKD, which may be associated with its ability to improve microbial composition, increase microbial diversity, and regulate SCFAs levels.

蜂蜜并不等同于糖,它在全世界范围内都具有促进健康的作用,如抗氧化、抗菌、抗炎和保肝等活性。然而,蜂蜜对高脂饮食诱发的慢性肾病(CKD)和肠道微生物群的潜在影响仍有待探索。本文采用高脂饮食诱导小鼠慢性肾脏病模型,并对肝脏、肾脏、脾脏指数、组织形态、生化指标、慢性肾脏病相关基因和肠道微生物多样性进行了分析。结果表明,蜂蜜治疗可明显抑制高脂饮食对小鼠肾脏造成的损伤,并改善疾病症状。血清 TC、TG、UA 和 BUN 以及肾组织中炎症相关蛋白 TNF-α 和 IL-6 水平也发生了显著变化。基因表达分析表明,蜂蜜的摄入量与肠道微生物群的多样性密切相关,它可以调节肠道微生物群的组成,增加微生物的多样性,尤其是双歧杆菌和 S24_7,并促进短链脂肪酸(SCFAs)的合成。总之,这项研究表明,蜂蜜对慢性肾功能衰竭具有预防和治疗作用,这可能与蜂蜜能够改善微生物组成、增加微生物多样性和调节 SCFAs 水平有关。
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引用次数: 0
Mesangial cell-derived CircRNAs in chronic glomerulonephritis: RNA sequencing and bioinformatics analysis. 慢性肾小球肾炎中间质细胞衍生的 CircRNA:RNA测序和生物信息学分析
IF 3 3区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-12-01 Epub Date: 2024-07-01 DOI: 10.1080/0886022X.2024.2371059
Ji Hui Fan, Xiao Min Li

Background: Circular RNAs (circRNAs) have been shown to play critical roles in the initiation and progression of chronic glomerulonephritis (CGN), while their role from mesangial cells in contributing to the pathogenesis of CGN is rarely understood. Our study aims to explore the potential functions of mesangial cell-derived circRNAs using RNA sequencing (RNA-seq) and bioinformatics analysis.

Methods: Mouse mesangial cells (MMCs) were stimulated by lipopolysaccharide (LPS) to establish an in vitro model of CGN. Pro-inflammatory cytokines and cell cycle stages were detected by Enzyme-linked immunosorbent assay (ELISA) and Flow Cytometry experiment, respectively. Subsequently, differentially expressed circRNAs (DE-circRNAs) were identified by RNA-seq. GEO microarrays were used to identify differentially expressed mRNAs (DE-mRNAs) between CGN and healthy populations. Weighted co-expression network analysis (WGCNA) was utilized to explore clinically significant modules of CGN. CircRNA-associated CeRNA networks were constructed by bioinformatics analysis. The hub mRNAs from CeRNA network were identified using LASSO algorithms. Furthermore, utilizing protein-protein interaction (PPI), gene ontology (GO), pathway enrichment (KEGG), and GSEA analyses to explore the potential biological function of target genes from CeRNA network. In addition, we investigated the relationships between immune cells and hub mRNAs from CeRNA network using CIBERSORT.

Results: The expression of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α was drastically increased in LPS-induced MMCs. The number of cells decreased significantly in the G1 phase but increased significantly in the S/G2 phase. A total of 6 DE-mRNAs were determined by RNA-seq, including 4 up-regulated circRNAs and 2 down-regulated circRNAs. WGCNA analysis identified 1747 DE-mRNAs of the turquoise module from CGN people in the GEO database. Then, the CeRNA networks, including 6 circRNAs, 38 miRNAs, and 80 mRNAs, were successfully constructed. The results of GO and KEGG analyses revealed that the target mRNAs were mainly enriched in immune, infection, and inflammation-related pathways. Furthermore, three hub mRNAs (BOC, MLST8, and HMGCS2) from the CeRNA network were screened using LASSO algorithms. GSEA analysis revealed that hub mRNAs were implicated in a great deal of immune system responses and inflammatory pathways, including IL-5 production, MAPK signaling pathway, and JAK-STAT signaling pathway. Moreover, according to an evaluation of immune infiltration, hub mRNAs have statistical correlations with neutrophils, plasma cells, monocytes, and follicular helper T cells.

Conclusions: Our findings provide fundamental and novel insights for further investigations into the role of mesangial cell-derived circRNAs in CGN pathogenesis.

背景:循环RNAs(circRNAs)已被证明在慢性肾小球肾炎(CGN)的发生和发展过程中起着关键作用,而它们从系膜细胞中提取并在CGN发病机制中的作用却鲜为人知。我们的研究旨在利用 RNA 测序(RNA-seq)和生物信息学分析探索系膜细胞衍生的 circRNAs 的潜在功能:方法:用脂多糖(LPS)刺激小鼠间质细胞(MMCs),建立 CGN 体外模型。通过酶联免疫吸附试验(ELISA)和流式细胞术实验分别检测促炎细胞因子和细胞周期阶段。随后,通过 RNA-seq 鉴定了差异表达的 circRNAs(DE-circRNAs)。GEO 微阵列用于鉴定 CGN 和健康人群之间差异表达的 mRNA(DE-mRNA)。利用加权共表达网络分析(WGCNA)来探索具有临床意义的 CGN 模块。通过生物信息学分析构建了CircRNA相关的CeRNA网络。利用 LASSO 算法识别了 CeRNA 网络中的中心 mRNA。此外,我们还利用蛋白质-蛋白质相互作用(PPI)、基因本体(GO)、通路富集(KEGG)和 GSEA 分析来探索 CeRNA 网络中靶基因的潜在生物学功能。此外,我们还利用 CIBERSORT 研究了免疫细胞与 CeRNA 网络中枢 mRNA 之间的关系:结果:在 LPS 诱导的 MMCs 中,促炎细胞因子 IL-1β、IL-6 和 TNF-α 的表达急剧增加。细胞数量在 G1 期明显减少,但在 S/G2 期明显增加。RNA-seq共测定了6个DE-mRNA,包括4个上调的circRNA和2个下调的circRNA。WGCNA分析从GEO数据库中的CGN人群中发现了1747个绿松石模块的DE-mRNA。然后,成功构建了包括 6 个 circRNA、38 个 miRNA 和 80 个 mRNA 的 CeRNA 网络。GO和KEGG分析结果显示,目标mRNA主要富集于免疫、感染和炎症相关通路。此外,利用 LASSO 算法筛选了 CeRNA 网络中的三个中心 mRNA(BOC、MLST8 和 HMGCS2)。GSEA分析显示,中枢mRNA与大量免疫系统反应和炎症通路有关,包括IL-5的产生、MAPK信号通路和JAK-STAT信号通路。此外,根据对免疫浸润的评估,中枢 mRNA 与中性粒细胞、浆细胞、单核细胞和滤泡辅助 T 细胞有统计学相关性:我们的研究结果为进一步研究间质细胞衍生的 circRNA 在 CGN 发病机制中的作用提供了基础性的新见解。
{"title":"Mesangial cell-derived CircRNAs in chronic glomerulonephritis: RNA sequencing and bioinformatics analysis.","authors":"Ji Hui Fan, Xiao Min Li","doi":"10.1080/0886022X.2024.2371059","DOIUrl":"10.1080/0886022X.2024.2371059","url":null,"abstract":"<p><strong>Background: </strong>Circular RNAs (circRNAs) have been shown to play critical roles in the initiation and progression of chronic glomerulonephritis (CGN), while their role from mesangial cells in contributing to the pathogenesis of CGN is rarely understood. Our study aims to explore the potential functions of mesangial cell-derived circRNAs using RNA sequencing (RNA-seq) and bioinformatics analysis.</p><p><strong>Methods: </strong>Mouse mesangial cells (MMCs) were stimulated by lipopolysaccharide (LPS) to establish an <i>in vitro</i> model of CGN. Pro-inflammatory cytokines and cell cycle stages were detected by Enzyme-linked immunosorbent assay (ELISA) and Flow Cytometry experiment, respectively. Subsequently, differentially expressed circRNAs (DE-circRNAs) were identified by RNA-seq. GEO microarrays were used to identify differentially expressed mRNAs (DE-mRNAs) between CGN and healthy populations. Weighted co-expression network analysis (WGCNA) was utilized to explore clinically significant modules of CGN. CircRNA-associated CeRNA networks were constructed by bioinformatics analysis. The hub mRNAs from CeRNA network were identified using LASSO algorithms. Furthermore, utilizing protein-protein interaction (PPI), gene ontology (GO), pathway enrichment (KEGG), and GSEA analyses to explore the potential biological function of target genes from CeRNA network. In addition, we investigated the relationships between immune cells and hub mRNAs from CeRNA network using CIBERSORT.</p><p><strong>Results: </strong>The expression of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α was drastically increased in LPS-induced MMCs. The number of cells decreased significantly in the G1 phase but increased significantly in the S/G2 phase. A total of 6 DE-mRNAs were determined by RNA-seq, including 4 up-regulated circRNAs and 2 down-regulated circRNAs. WGCNA analysis identified 1747 DE-mRNAs of the turquoise module from CGN people in the GEO database. Then, the CeRNA networks, including 6 circRNAs, 38 miRNAs, and 80 mRNAs, were successfully constructed. The results of GO and KEGG analyses revealed that the target mRNAs were mainly enriched in immune, infection, and inflammation-related pathways. Furthermore, three hub mRNAs (BOC, MLST8, and HMGCS2) from the CeRNA network were screened using LASSO algorithms. GSEA analysis revealed that hub mRNAs were implicated in a great deal of immune system responses and inflammatory pathways, including IL-5 production, MAPK signaling pathway, and JAK-STAT signaling pathway. Moreover, according to an evaluation of immune infiltration, hub mRNAs have statistical correlations with neutrophils, plasma cells, monocytes, and follicular helper T cells.</p><p><strong>Conclusions: </strong>Our findings provide fundamental and novel insights for further investigations into the role of mesangial cell-derived circRNAs in CGN pathogenesis.</p>","PeriodicalId":20839,"journal":{"name":"Renal Failure","volume":"46 2","pages":"2371059"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC467094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fractionated plasma separation and adsorption integrated with continuous veno-venous hemofiltration in patients with acute bipyridine herbicide poisoning. 急性联吡啶类除草剂中毒患者的分馏血浆分离和吸附与连续静脉-静脉血液滤过相结合。
IF 3 3区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-12-01 Epub Date: 2024-07-05 DOI: 10.1080/0886022X.2024.2374013
Jian-Hua Dong, Minghong Zhang, Xi Yang, Bian Wu, Li Huang, Chuan Li, Yongchun Ge

Objective: To evaluate the clinical efficacy and safety of fractionated plasma separation and adsorption combined with continuous veno-venous hemofiltration (FPSA-CVVH) treatment in patients with acute bipyridine herbicide poisoning.

Methods: A retrospective analysis of 18 patients with acute bipyridine herbicide poisoning was conducted, of which 9 patients were poisoned by diquat and 9 patients by paraquat. All patients underwent FPSA-CVVH treatment. The serum cytokine levels in pesticide-poisoned patients were assessed. The efficacy of FPSA-CVVH in eliminating cytokines, the 90-d survival rate of poisoned patients, and adverse reactions to the treatment were observed.

Results: Fourteen patients (77.8%) had acute kidney injuries and 10 (55.6%) had acute liver injuries. The serum cytokine levels of high mobility group protein B-1 (HMGB-1), interleukin-6 (IL-6), IL-8, interferon-inducible protein-10 (IP-10), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1β (MIP-1β) were significantly elevated. A total of 41 FPSA-CVVH treatment sessions were administered. After a single 8-h FPSA-CVVH treatment, the decreases in HMGB-1, IL-6, IL-8, IP-10, MCP-1, and MIP-1β were 66.0%, 63.5%, 73.3%, 63.7%, 53.9%, and 54.1%, respectively. During FPSA-CVVH treatment, one patient required a filter change due to coagulation in the plasma component separator, and one experienced a bleeding adverse reaction. The 90-d patient survival rate was 50%, with 4 patients with diquat poisoning and 5 patients with paraquat poisoning, and both liver and kidney functions were restored to normal.

Conclusion: Cytokine storms may play a significant role in the progression of multiorgan dysfunction in patients with acute bipyridine herbicide poisoning. FPSA-CVVH can effectively reduce cytokine levels, increase the survival rate of patients with acute bipyridine herbicide poisoning, and decrease the incidence of adverse events.

目的评估分馏血浆分离吸附联合持续静脉-静脉血液滤过(FPSA-CVVH)治疗急性联吡啶类除草剂中毒患者的临床疗效和安全性:对18例急性联吡啶类除草剂中毒患者进行了回顾性分析,其中9例为敌草快中毒,9例为百草枯中毒。所有患者均接受了 FPSA-CVVH 治疗。对农药中毒患者的血清细胞因子水平进行了评估。观察了 FPSA-CVVH 消除细胞因子的疗效、中毒患者的 90 天存活率以及治疗后的不良反应:结果:14 名患者(77.8%)出现急性肾损伤,10 名患者(55.6%)出现急性肝损伤。血清中高迁移率基团蛋白 B-1 (HMGB-1)、白细胞介素-6 (IL-6)、IL-8、干扰素诱导蛋白-10 (IP-10)、单核细胞趋化蛋白-1 (MCP-1)、巨噬细胞炎症蛋白-1β (MIP-1β)等细胞因子水平明显升高。共进行了 41 次 FPSA-CVVH 治疗。单次 8 小时 FPSA-CVVH 治疗后,HMGB-1、IL-6、IL-8、IP-10、MCP-1 和 MIP-1β 的降幅分别为 66.0%、63.5%、73.3%、63.7%、53.9% 和 54.1%。在FPSA-CVVH治疗期间,一名患者因血浆成分分离器中的凝血而需要更换过滤器,一名患者出现出血不良反应。90天存活率为50%,其中4例为敌草快中毒,5例为百草枯中毒,肝肾功能均恢复正常:结论:细胞因子风暴可能在急性联吡啶类除草剂中毒患者多器官功能障碍的发展过程中起着重要作用。FPSA-CVVH可有效降低细胞因子水平,提高急性联吡啶类除草剂中毒患者的存活率,降低不良反应的发生率。
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引用次数: 0
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Renal Failure
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