急性心肌梗死患者PCI术后心室重构患者血清Hcy、CysC、MMP-1、NGAL的表达及临床意义

摘要 目的：观察急性心肌梗死（AMI）患者经皮冠脉介入术（PCI）术后心室重构患者血清同型半胱氨酸（Hcy）、胱抑素C（CysC）、基质金属蛋白酶-1（MMP-1）、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）的表达及临床意义。方法：选取2018年3月~2020年9月期间我院收治的AMI患者70例。根据PCI术后是否发生心室重构将其分为无心室重构组（n=49）和心室重构组（n=21）。检测患者血清MMP-1、Hcy、NGAL、CysC水平及心功能指标[左室后壁厚度( LVPWT)、左室舒张末期内径( LVEDD)、左室射血分数( LVEF)、室间隔厚度( IVST)]。分析血清MMP-1、Hcy、NGAL、CysC水平与心功能指标的相关性。分析AMI患者PCI术后心室重构的影响因素。结果：心室重构组血清MMP-1、Hcy、NGAL、CysC水平均高于无心室重构组（P<0.05）;LVEDD、IVST、 LVPWT均大于无心室重构组,LVEF低于无心室重构组（P<0.05）。Pearson相关性分析结果显示：血清MMP-1、Hcy、NGAL、CysC水平和LVEDD、IVST、 LVPWT均呈正相关,而与LVEF呈负相关（P<0.05）。单因素分析结果显示：两组患者梗死部位、心律失常情况、单核细胞（MO）、肌酸激酶同功酶（CK-MB）、发病到开通梗死相关动脉时间组间对比差异均有统计学意义（P<0.05）。多因素Logistic回归分析结果显示：梗死部位为前壁、发生心律失常以及高水平的MO、CK-MB、MMP-1、Hcy、CysC均是AMI患者PCI术后发生心室重构的危险因素（P<0.05）。结论：血清MMP-1、Hcy、NGAL、CysC表达均与AMI患者PCI术后的心室重构密切相关,检测以上指标水平可对AMI患者PCI术后心室重构的预测和防治提供一定参考。     

The significance of combined detection of CysC,urinary mAlb and β2-MG in diagnosis of the early renal injury in pregnancy-induced hypertension syndrome

ObjectiveTo elaborate the significance of combined detection of cystatin C, urinary micro-albumin (mAlb) and β₂-microglobulin (β₂-MG) in diagnosis of the early renal injury in pregnancy-induced hypertension syndrome.MethodsA total of 120 patients with pregnancy-induced hypertension syndrome who were admitted to this hospital for treatment between November 2015 and October 2018 were enrolled as subjects, and divided into the control group (without complication of renal injury, n = 76) and the observation group (with complication of renal injury, n = 44) according to the complications of early renal injury. Furthermore, 60 patients who participated in the antenatal care in this hospital were enrolled as the normal subjects (normal group). Automatic biochemistry analyzer was utilized to measure CysC, urinary mAlb and β₂-MG in serum to evaluate the specificity, sensitivity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of single or combined measurements of these indexes in diagnosis of the early renal injury in pregnancy-induced hypertension syndrome.ResultsIn the observation group, the levels of CysC, urinary mAlb and β₂-MG were higher than those in the control group, while the levels in the normal group were the lowest (P < 0.05). Combined measurement of CysC, urinary mAlb and β₂-MG showed a higher accuracy (90.0%) in diagnosis of the early renal injury in pregnancy-induced hypertension syndrome than the single measurements, and the difference had statistical significance (P < 0.05). Besides, the sensitivity, specificity, PPV and NPV of the combined measurements were 94.59%, 87.30%, 81.40% and 94.49%, slightly higher than the single measurements, with no statistical significance in differences (P > 0.05).ConclusionCysC, urinary mAlb and β₂-MG can reflect the renal injury effectively, and the combined measurements shows potent accuracy in diagnosis of the early renal injury in pregnancy-induced hypertension syndrome, thereby providing the scientific evidence for early diagnosis and stipulation of rational therapeutic regimen and improving the pregnancy outcome.     

血清Hcy与CysC 对早期2型糖尿病肾病的临床诊断价值分析

目的:分析血清同型半胱氨酸(Hcy)与胱抑素C(CysC)对早期2型糖尿病肾病的临床诊断价值。方法:选择2013年5月至2016年5月我院收治的早期糖尿病肾病患者60例为A组,选取同期我院收治的单纯糖尿病患者60例为B组,另选我院同期健康体检者60例为C组,检测三组的血清Hcy、CysC、血尿素氮(BUN)、血肌酐(Scr)、尿蛋白排泄率(UAER)。结果:与C组比较,A组和B组的BUN、Scr、UAER均升高(P0.05),A组的UAER高于B组(P0.05),但A组的BUN、Scr与B组比较,组间差异无统计学意义(P 0.05)。A组的病程明显高于B组(P0.05)。与C组比较,A组Hcy与CysC水平升高(P0.05),B组的Hcy水平升高(P0.05),CysC水平升高,但差异无统计学意义(P 0.05);与B组比较,A组Hcy与CysC水平升高(P0.05)。A组的Hcy、CysC、Hcy+CysC阳性率均明显高于B组和C组(P0.05),B组Hcy、CysC、Hcy+CysC阳性率均明显高于C组(P0.05);A组和B组的Hcy+CysC联合检测的阳性率高于Hcy、CysC的单独检测阳性率(P0.05)。Hcy与病程、BUN、Scr、UAER均呈正相关,相关系数r=0.650、0.488、0.596、0.761,P0.05,CysC与病程、BUN、Scr、UAER均呈正相关,相关系数r=0.681、0.502、0.601、0.825,P0.05。结论:血清Hcy与CysC可及时、准确的反应2型糖尿病患者的肾损伤情况,从而有利于早期2型糖尿病肾病的及时检出。     

2型糖尿病患者微血管病变与血清代谢学指标的关系

目的:探讨2型糖尿病(T2DM)患者微血管病变与血清代谢学指标的关系。方法:选择我院于2015年7月~2016年7月间收治的T2DM患者共96例,按是否存在微血管病变分为观察组(n=43,存在微血管病变)及对照组(n=53,无微血管病变)。检测并对比两组患者血清中三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、空腹血糖(FBG)、糖化血红蛋白(HbA1C)、同型半胱氨酸(Hcy)、血清胱抑素C(CysC)及血管内皮生长因子(VEGF)水平,并采用logistic回归分析T2DM微血管病变的危险因素。结果:观察组病程、吸烟率高于对照组,差异有统计学意义(P0.05);观察组TG、LDL、HbA1C、CysC、Hcy、VEGF水平均高于对照组,差异均有统计学意义(P0.05);两组TC、HDL水平比较,差异无统计学意义(P0.05);经logistic回归分析显示,病程、CysC、Hcy、VEGF为微血管病变的危险因素(OR=1.975,3.643,4.054,4.214,P0.05)。结论:CysC、Hcy、VEGF为微血管病变的危险因素,对其水平的检测有助于早期T2DM微血管病变诊断及治疗。     

Intracerebroventricular administration of Cystatin C ameliorates disease in SOD1‐linked amyotrophic lateral sclerosis mice

Cystatin C (CysC) is a major protein component of Bunina bodies, which are a pathological hallmark observed in the remaining motor neurons of patients with amyotrophic lateral sclerosis (ALS). Dominant mutations in the SOD1 gene, encoding Cu/Zn superoxide dismutase (SOD1), are causative for a subset of inherited ALS cases. Our previous study showed that CysC exerts a neuroprotective effect against mutant SOD1‐mediated toxicity in vitro; however, in vivo evidence of the beneficial effects mediated by CysC remains obscure. Here we examined the therapeutic potential of recombinant human CysC in vivo using a mouse model of ALS in which the ALS‐linked mutated SOD1 gene is expressed (SOD1^G93A mice). Intracerebroventricular administration of CysC during the early symptomatic SOD1^G93A mice extended their survival times. Administered CysC was predominantly distributed in ventral horn neurons including motor neurons, and induced autophagy through AMP‐activated kinase activation to reduce the amount of insoluble mutant SOD1 species. Moreover, PGC‐1α, a disease modifier of ALS, was restored by CysC through AMP‐activated kinase activation. Finally, the administration of CysC also promoted aggregation of CysC in motor neurons, which is similar to Bunina bodies. Taken together, our findings suggest that CysC represents a promising therapeutic candidate for ALS.

     

颈部肿瘤患者围术期血清唾液酸、微量元素及CD44v6、CysC、NO、TGF-β、VEGF的变化研究

目的：分析研究颈部肿瘤患者围术期血清唾液酸、微量元素及CD44v6、CysC、NO、TGF—β、VEGF的变化情况。方法：选取2012年1月～2013年2月于本院采用手术治疗的34例颈部肿瘤患者为观察组,将同时期于本院进行体检的34名健康人员选为对照组,然后将观察组术前1d、术后1、3、5、7d和对照组的血清唾液酸、微量元素及CD44v6、CysC、NO、TGF-β、VEGF水平进行检测与比较。结果：观察组术前1d的血清唾液酸、Cu、Cu／Zn及CD44v6、CysC、NO、TGF-β、VEGF均高于对照组,而观察组上述指标术后1、3、5、7d明显低于术前1d,观察组术前1d血清Se、zn低于对照组,术后1、3、5、7d高于对照组,均有显著性差异（P〈0．05）。结论：颈部肿瘤患者围术期血清唾液酸、微量元素及CD44v6、CysC、NO、TGF-β、VEGF的变化较为明显,可有效反应疾病的发展转归。     

比较沙库巴曲缬沙坦与缬沙坦对慢性心衰患者心肾功能的影响

目的:比较沙库巴曲缬沙坦与缬沙坦在慢性心力衰竭(Chronic heart failure, CHF)患者治疗中对心功能及肾功能的影响。方法:按WHO诊断标准随机选择CHF患者,对照组30例,给予缬沙坦80 mg/qd起,2-4周后增至160 mg/qd;研究组30例,给予沙库巴曲缬沙坦100 mg/bid,2-4周后增至200 mg/bid。治疗8周后,比较两组治疗后LVEF、LVESD和LVEDD的变化,以及对Scr、Cys C的影响。结果:(1)两组患者的性别、年龄、NYHA心功能分级等一般情况,以及治疗前LVEF、LVESD、LVEDD、Scr、Cys C等指标比较均无显著性差异(P0.05),具有可比性。(2)治疗8周后,对照组的LVEF较治疗前显著升高(38.87±6.95%VS.34.73±7.89%,P0.05),LVESD、LVEDD均较治疗前显著降低(44.43±8.26 mm VS.50.77±8.31 mm,P0.05;54.77±5.84 mm VS.59.87±7.57 mm,P0.05),Cys C较治疗前显著降低(1.00±0.33 mg/LVS.1.27±0.52 mg/L,P0.05),Scr较治疗前无显著性差异(82.24±30.38μmol/LVS.91.19±36.81μmol/L,P0.05)。研究组的LVEF较治疗前显著升高(38.70±7.29%VS.33.53±9.12%,P0.05),LVESD、LVEDD均较治疗前显著降低(43.33±9.10 mm VS.49.47±6.84 mm,P0.05;54.53±6.20 mm VS.60.23±8.30 mm,P0.05),Cys C较治疗前显著降低(1.01±0.26 mg/LVS.1.32±0.53 mg/L,P0.05),Scr较治疗前无显著性差异(84.31±32.25μmol/LVS.94.43±38.73μmol/L,P0.05)。比较两组治疗后各项指标均无显著性差异(P0.05)。结论:在CHF的治疗过程中,沙库巴曲缬沙坦与缬沙坦均能改善心功能,且在短时间内具有一定的肾功能保护作用。     

A metabolomics-based approach for predicting stages of chronic kidney disease

Chronic kidney disease (CKD) is a major epidemiologic problem and a risk factor for cardiovascular events and cerebrovascular accidents. Because CKD shows irreversible progression, early diagnosis is desirable. Renal function can be evaluated by measuring creatinine-based estimated glomerular filtration rate (eGFR). This method, however, has low sensitivity during early phases of CKD. Cystatin C (CysC) may be a more sensitive predictor. Using a metabolomic method, we previously identified metabolites in CKD and hemodialysis patients. To develop a new index of renal hypofunction, plasma samples were collected from volunteers with and without CKD and metabolite concentrations were assayed by quantitative liquid chromatography/mass spectrometry. These results were used to construct a multivariate regression equation for an inverse of CysC-based eGFR, with eGFR and CKD stage calculated from concentrations of blood metabolites. This equation was able to predict CKD stages with 81.3% accuracy (range, 73.9–87.0% during 20 repeats). This procedure may become a novel method of identifying patients with early-stage CKD.     

miR-204/miR-211 downregulation contributes to Candidemia-induced kidney injuries via derepression of Hmx1 expression

Aims

This study was aimed to exploit the role of heme oxygenase Hmx1 and the potential miRNA mechanisms in the kidney injuries induced by urinary tract infection by Candida species/Candidemia.

Main methods

We employed a mouse model of systemic Candidiasis by injection of the Candida albicans strain SC5314 into C57BL/6 mice. Kidney injuries were assessed by measuring serum cystatin C (CysC), serum β₂-microglobulin (β₂-MG) and blood urea nitrogen (BUN). Validation of miRNA target gene was conducted by luciferase reporter gene assay, Western blot analysis and real-time RT-PCR.

Key findings

We showed here that Candidemia caused significant downregulation of microRNAs miR-204 and miR-211. In sharp contrast, Hmx1 expression was remarkably upregulated, particularly at the protein level. Computational analysis predicted Hmx1 as a target gene for both miR-204 and miR-211 that share the same seed site sequence. We then experimentally validated the targeting relationship between miR-204/miR-211 and Hmx1, which explains the reciprocal changes of expression of miR-204/miR-211 and Hmx1 in Candidemia. Administration of miR-204/miR-211 mimics substantially downregulated Hmx1 and mitigated the severity of the kidney injuries induced by Candidemia, as reflected by improved renal glomerular filtration rate (GFR) determined by serum cystatin C (CysC), serum β₂-microglobulin (β₂-MG) and blood urea nitrogen (BUN). Knockdown of miR-204/miR-211 worsened while forced expression of miR-204/miR-211 ameliorated kidney injuries in mice with systemic Candidiasis.

Significance

Our findings indicate that miR-204/miR-211 downregulation accounts at least partially for the Hmx1 upregulation and the miR-204/miR-211–Hmx1 signaling axis may contribute to immune-suppression in the host thereby the Candidemia-induced kidney dysfunction.     

美金刚联合普拉克索治疗帕金森患者临床疗效及对CysC、Hcy水平影响

目的:探究美金刚联合普拉克索在治疗帕金森患者中的临床疗效,并就治疗对患者胱抑素C(cystatin C,CysC)以及血同型半胱氨酸(homocysteine,Hcy)水平的影响。方法:选择2018年1月至2020年1月于我院接受治疗的98例帕金森患者,随机数字表法均分为两组(每组各49例),对照组单纯接受美金刚治疗,研究组在对照组基础上加用普拉克索进行治疗,对比两组治疗有效率,治疗前后CysC、Hcy水平,以及治疗前后简易智能精神状态检查量表(mini mental state examination,MMSE)以及帕金森病评定量表III(parkinson comprehensive rating scale,UPDRS III)评分,最后对两组患者治疗中不良反应发生率进行统计对比。结果:(1)研究组患者治疗有效率明显高于对照组患者(P0.05);(2)治疗前两组患者CysC、Hcy水平对比差异不具有统计学意义(P0.05),治疗后研究组患者CysC、Hcy水平低于对照组(P0.05);(3)治疗前两组患者MMSE及UPDRS III量表评分对比差异不具有统计学意义(P0.05),治疗后研究组患者MMSE得分高于对照组,UPDRS III量表评分低于对照组(P0.05);(4)两组治疗不良反应诸如胃肠道反应、嗜睡、体位性低血压等对比无差异(P0.05)。结论:美金刚联合普拉克索对帕金森具有较好的治疗效果,能够显著改善患者认知及运动功能,降低CysC、Hcy水平,同时治疗安全性较高。