UNASSIGNED: Recent studies have shown that the triglyceride glucose index (TyG) and cystatin C (CysC) are closely related to cardiovascular disease, but there is limited research on the prognosis of patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). The aim of this study was to explore the predictive value of the combination of the TyG index and CysC in predicting major adverse cardiovascular events (MACEs) in ACS patients who underwent PCI.
UNASSIGNED: This retrospective study included 319 ACS patients who underwent PCI. The clinical endpoint was the occurrence of MACEs, including all-cause mortality, heart failure, non-fatal myocardial infarction, target vessel revascularization, and angina requiring hospitalization. Patients were classified into MACEs (65 cases) and non-MACEs (254 cases) groups. Univariate factor and multivariate analysis were used to identify predictors of MACEs. The receiver operating curve (ROC) of the prediction model of MACEs was determined. Additionally, the net reclassification improvement and integrated discrimination improvement indexes were calculated to further assess the additional predictive value of the risk factors for MACEs. Subgroup and interaction analysis between the TyG index combined with CysC and MACEs were conducted in various subgroups. Patients were stratified according to the optimal cutoff point value of the TyG index and the CysC determined by ROC curve analysis. The Kaplan-Meier analysis method was used to construct a survival curve 1 year after PCI.
UNASSIGNED: During a median follow-up period of 14 months, 65 (20.38%) patients had experienced at least one primary endpoint event. Multivariate logistic regression analysis indicated that the TyG index and CysC were independently associated with an increased risk of MACEs after PCI (OR, 2.513, 95% CI 1.451-4.351, P= 0.001; and OR, 4.741, 95% CI 1.344-16.731, P=0.016, respectively). The addition of the TyG index and CysC to the baseline risk model had the strongest incremental effect for predicting MACEs in terms of the C-statistic from 0.789 (95% CI 0.723-0.855, P<0.001) to 0.799 (95% CI 0.733-0.865, P<0.001). Furthermore, Kaplan-Meier analysis demonstrated that a TyG index greater than 9.325 and a CysC value greater than 1.065 mg/ml were significantly associated with an increased risk of MACEs (log-rank, all P < 0.01).
UNASSIGNED: The TyG index predicts MACEs after PCI in patients with ASC independent of known cardiovascular risk factors. Adjustment of the CysC by the TyG index further improves the predictive ability for MACEs in patients with ACS undergoing PCI. Thus, both of them are expected to become new prognostic indicators for MACEs in patients with ACS after PCI.

Background Human nephrin (hNeph) (podocyte protein) has been known to be involved in both the formation and maintenance of the slit diaphragm (SD) and also acts as a hub protein in the podocyte by modulating cell polarity, cell survival, cell adhesion, cytoskeletal organization, mechano-sensing, and SD turn-over. Methodology In the present investigation, we aimed to analyse the hNeph and mouse nephrin (mNeph) and their interactions with 13 proteins using the molecular docking method. The 13 selected human proteins which include matrix metalloproteinases (MMP 2 and 9), retinol-binding proteins (RBP 3 and 4), kallikrein 1 (KLK 1), uromodulin, insulin-like growth factor binding protein 7 (IGFBP7), cystatin C, podocin, beta arrestin 1, vang-like protein 2 (VANGL2), dynamin 1, and tensin-like C1 domain-containing phosphatase (TENC1) were studied on the docking analysis of hNeph and mNeph by using the HDOCK (protein-protein) docking method. In addition, the physicochemical (PC) properties of 15 proteins were performed using the ProtParam web server. Results In the present investigation, five chosen human proteins, namely, IGFBP7, cystatin C, podocin, VANGL2, and TENC1, have exhibited theoretical isoelectric point (PI) values greater than 7.0. The protein-protein docking analysis has shown that hKLK and hVANGL2 exhibited the maximum docking score of -206.39 kcal/mol and -329.28 (kcal/mol) with the target proteins mNeph and hNeph, respectively. Conclusions Thus, the current finding highlights the interactions of hNeph and mNeph with 13 chosen proteins, which may help in renal disease management.

The prevalence of chronic kidney disease (CKD) continues to rise globally, paralleled by an increase in associated morbidity and mortality, as well as significant implications for patient quality of life and national economies. Chronic kidney disease often progresses unrecognized by patients and physicians, despite diagnosis relying on two simple laboratory measures: estimated glomerular filtration rate (eGFR) and urine analysis. GFR measurement has been grounded in renal physiology, specifically the concept of clearance, with creatinine identified as a suitable endogenous marker for estimating creatinine clearance (CrCl). On this foundation, various equations have been developed to calculate CrCl or estimated GFR (eGFR) using four variables that incorporate creatinine and certain demographic information, such as sex and age. However, creatinine measurement requires standardization to minimize assay variability across laboratories. Moreover, the accuracy of these equations remains contentious in certain patient subgroups. For these reasons, additional mathematical models have been devised to enhance CrCl estimation, for example, when urine collection is impractical, in elderly or debilitated patients, and in individuals with trauma, diabetes, or obesity. Presently, eGFR in adults can be immediately measured and reported using creatinine-based equations traceable through isotope dilution mass spectrometry. In conclusion, leveraging insights from renal physiology, eGFR can be employed clinically for early diagnosis and treatment of CKD, as well as a public health tool to estimate its prevalence.

The use of 3 biomarkers - cystatin-C (Cys-C), retinol-binding protein (RBP), and ischemia-modified albumin (IMA) - for the clinical classification and outcome of coronary heart disease (CHD) has not been adequately evaluated. We explored the serum levels of these 3 markers and evaluated their diagnostic and prognostic values in patients with CHD. This retrospective case-control study, conducted between June 2017 and June 2018, included 201 patients with CHD hospitalized at the Henan Provincial People\'s Hospital and 127 healthy individuals from Henan Provincial People\'s Hospital as controls. Cys-C, RBP, IMA levels, and other laboratory parameters in the 2 groups were determined, and patient outcomes were analyzed. Cys-C, RBP, and IMA levels were higher in the case group than in the control group (P < .05). Logistic regression analysis confirmed that these 3 biomarkers were independent risk factors for CHD. Each indicator has clinical significance in the diagnosis and prognosis of CHD, with RBP being the most significant. The AUC value for CHD detection using a combination of the 3 indicators was 0.783, and the sensitivity and specificity values were 78% and 74.6%, respectively. Simultaneous detection of Cys-C, RBP, and IMA could be an optimal method for early diagnosis and prognosis of CHD.

The exposure to modifiable risk factors at young ages have been linked to premature fatal and non-fatal cardiovascular and kidney outcomes. The use of urinary metabolomics has shown strong predictability of kidney function and cardiovascular disease (CVD). We therefore determined the associations between estimated glomerular filtration rate (eGFR) and urinary metabolites in young adults with and without CVD risk factors. Apparently healthy Black and White sexes were included (aged 20-30 years) and categorised by the presence or absence of risk factors, i.e., obesity, physical inactivity, smoking, excessive alcohol intake, masked hypertension, hyperglycemia, dyslipidemia and low socio-economic status, forming the CVD risk group (N = 1036), CVD risk clusters (i.e. presenting with 1 CVD risk factor (N = 344), 2 CVD risk factors (N = 360) and 3 + CVD risk factors (N = 332)) and the control group (N = 166). eGFR was calculated with CKD-EPI equations. A targeted metabolomics approach using liquid chromatography-tandem mass spectrometry was used to measure amino acids and acylcarnitines. Lower cystatin C-based eGFR were indicated in the CVD risk group, 2 and 3 + CVD risk clusters compared to the control group (all P ≤ 0.033). In the CVD risk group, eGFR associated positively with histidine, lysine, asparagine, glycine, serine, glutamine, dimethylglycine, threonine, alanine, creatine, cystine, methionine, tyrosine, pyroglutamic acid, leucine/isoleucine, aspartic acid, tryptophan, glutamic acid, free carnitine, acetylcarnitine, propionylcarnitine, isovalerylcarnitine, octanoylcarnitine and decanoylcarnitine (all P ≤ 0.044), with similar results found in the CVD risk clusters, particularly the 2 CVD risk cluster. eGFR was positively associated with metabolites linked to aromatic amino acid and branched-chain amino acid metabolism, energy metabolism and oxidative stress. These findings may indicate altered reabsorption of these metabolites or altered metabolic regulation to preserve renal health in the setting of CVD risk factors at this young age without established CVD.

UNASSIGNED: Metabolic syndrome (MetS), characterized by central obesity, insulin resistance, dyslipidemia, and hypertension, affects 20-25% of the global population. The creatinine-to-cystatin C ratio (CCR) is an indicator of skeletal muscle mass. While CCR may play a role in MetS development, sex differences in these associations are not fully understood. Therefore, this study aimed to investigate how CCR levels are associated with MetS in a Chinese adult population, focusing on possible sex disparities.
UNASSIGNED: We conducted a retrospective cross-sectional analysis of 9,376 adults from Xiamen Chang Gung Hospital between 2014 to 2016. We examined the relationship between CCR and MetS, adjusting for cardiometabolic risk factors.
UNASSIGNED: The prevalence of MetS was 24.7% in males and 18.0% in females. Interestingly, we observed significant sex differences in the association between CCR quartiles and MetS. Females in the lowest CCR quartile had a significantly higher risk of MetS (odds ratio=1.84). Receiver operating characteristic curve analysis revealed acceptable diagnostic power of CCR for MetS in females (area under the curve=0.65) but not in males.
UNASSIGNED: Our findings suggest that CCR is an independent risk factor for MetS in females, highlighting the importance of sex-specific assessments when evaluating MetS risk.

This review examines the reliability of cystatin C as a biomarker for kidney function in paediatric populations. Chronic kidney disease (CKD) affects a significant number of children globally, leading to severe health complications such as anaemia, hypertension, and growth disorders. Traditionally, kidney function has been assessed using the estimated glomerular filtration rate derived from serum creatinine, though this method is flawed due to variability in muscle mass, age, gender, and diet. Cystatin C offers an alternative as it is less influenced by these factors. Evidence from various studies indicates that cystatin C provides a more accurate assessment of kidney function, especially in neonates and children with urinary tract malformations. Additionally, it is more reliable in early detection of acute kidney injury in paediatric intensive care units. Despite its potential, cystatin C is not yet widely adopted in clinical guidelines, primarily due to a lack of large-scale paediatric studies. Nonetheless, existing research supports its utility in providing a consistent and precise measure of kidney function across different paediatric age groups, suggesting that it could enhance early diagnosis and management of CKD in children if more extensive validation studies are conducted.

OBJECTIVE: To analyze the relationship between serum cystatin C (CysC), β2-microglobulin (β2-MG) and the efficacy of demethylation therapy in patients with acute myeloid leukemia (AML).
METHODS: A prospective cohort study was conducted on 98 AML patients admitted to the Affiliated Hospital of Inner Mongolia Medical University from February 2019 to January 2022. All patients were treated with decitabine (DAC) + HAG regimen, 28 days as a course and treated for 3-4 courses. At the end of each course of treatment, the treatment effect of the patients was evaluated, and the patients who achieved complete remission (CR) transferred to consolidation therapy, while the patients who did not reach CR at the end of the course of treatment were considered as treatment failure. The examination items before treatment include routine blood parameters, serum CysC, and β2-MG, and general clinical data of the patients were collected. According to the statistical results, logistic regression model was used to analyze the relationship between serum CysC, β2-MG and the efficacy of demethylation therapy in AML patients. The ROC curves were drawn, and the predictive efficacy of serum CysC, β2-MG on demethylation therapy in AML patients was evaluated by the area under the curve (AUC).
RESULTS: Of the 98 AML patients enrolled in the study, 5 cases were excluded during the treatment period, and 93 cases finally completed the chemotherapy courses. Among them, 23 patients achieved CR after the initial induction chemotherapy (course 1-2), and 11 patients achieved CR after the re-induction chemotherapy (course 3-4). The success rate of demethylation therapy was 36.56 % (34/93). Compared with the patients in treatment success group, patients in treatment failure group had a higher proportion of intermediate- and adverse-risk, lower levels of platelet (PLT) and hemoglobin (Hb), and higher expression levels of serum CysC and β2-MG, all of which were statistically significant (P < 0.05). Logistic regression analysis showed that high expression of serum CysC, β2-MG and adverse-risk were independent risk factors for failure of demethylation treatment in AML patients (OR >1, P < 0.05). The ROC curves showed that the AUC values of serum CysC, β2-MG alone and combined in predicting the efficacy of demethylation therapy in AML patients were 0.788, 0.785 and 0.834, respectively.
CONCLUSIONS: The failure of demethylation therapy in AML patients is related to the high expression of serum CysC and β2-MG, and detection of serum CysC and β2-MG before treatment can predict the risk of demethylation therapy failure in AML patients.
UNASSIGNED: 血清CysC、β2-MG与急性髓系白血病患者去甲基化治疗效果的关系.
UNASSIGNED: 分析血清胱抑素C（CysC）、β2-微球蛋白（β2-MG）与急性髓系白血病（AML）患者去甲基化治疗效果的关系。.
UNASSIGNED: 使用前瞻性队列研究方法，纳入2019年2月-2022年1月内蒙古医科大学附属医院收治的98例AML患者进行研究，全部患者均接受地西他滨（DAC）+HAG方案治疗，以28 d为1个疗程，治疗3-4疗程。每个疗程结束时评估患者的治疗效果，达到完全缓解（CR）的患者进入巩固治疗，全部疗程结束未达到CR的患者视为治疗失败。治疗前检查项目包括血常规参数、血清CysC、β2-MG，并统计患者一般临床资料。根据统计结果，使用logistic回归分析血清CysC、β2-MG与AML患者去甲基化治疗效果的关系；绘制受试者工作特征（ROC）曲线，以曲线下面积（AUC）评估血清CysC、β2-MG对AML患者去甲基化治疗效果的预测效能。.
UNASSIGNED: 入组98例AML患者，治疗期间5例被剔除，最终93例患者完成化疗疗程，其中23例初次诱导化疗（1-2疗程）达到CR，再诱导化疗（3-4疗程）后11例达到CR，治疗成功率为36.56%（34/93）。去甲基化治疗失败患者预后不良、预后中等占比高于治疗成功患者，血小板（PLT）、血红蛋白（Hb）水平低于治疗成功患者，血清CysC、β2-MG表达水平高于治疗成功患者，差异有统计学意义（P < 0.05）。logistic回归分析显示，血清CysC、β2-MG高表达及预后不良是AML患者去甲基化治疗失败的独立危险因素（OR >1，P < 0.05）。ROC曲线显示，血清CysC、β2-MG单独及联合预测AML患者去甲基化治疗效果的AUC值分别为0.788、0.785、0.834。.
UNASSIGNED: AML患者去甲基化治疗失败与血清CysC、β2-MG高表达有关，治疗前检测血清CysC、β2-MG能够预测AML患者去甲基化治疗失败风险。.

Former Extremely Low Birthweight (ELBW) neonates suffer from adverse renal and cardiovascular outcomes later in life. Less is known about additional perinatal risk factors for these adverse outcomes which we have investigated in this study. We compared renal outcome between ELBW children and controls, to find perinatal risk factors for poorer renal outcome and to unveil associations between kidney function and blood pressure. This study included 93 former ELBW children and 87 healthy controls with a mean age of 11 years at assessment. We measured cystatin C-based estimated glomerular filtration rate (eGFR) and blood pressure. Blood pressure and eGFR levels were compared between cases and controls. We subsequently investigated perinatal risk factors for adverse outcome amongst ELBW children. ELBW children have significantly higher blood pressure (mean SBP percentile 75th vs. 47th, p <0.001) and lower mean eGFR (94 vs. 107 ml/min/1.73 m2, p = 0.005) compared to the control group. Elevated blood pressure did not correlate with perinatal characteristics and none of them had microalbuminuria. ELBW children with eGFR <90 ml/min/1.73 m2 were ventilated longer (17 vs. 9 days, p = 0.006), more frequently male (OR = 3.33, p = 0.055) and tended to suffer more from intraventricular hemorrhage (40% vs. 15.8%, p = 0.056). There was no association between blood pressure and kidney dysfunction.
CONCLUSIONS: Understanding risk profiles for unfavorable outcomes may help to identify children at increased risk for kidney dysfunction. Poorer eGFR was associated with longer ventilation, male sex, and intra-ventricular hemorrhage but not with blood pressure. This knowledge can lead to safer neonatal therapeutic regimens for ELBW infants, a more intensive follow-up and earlier treatment initiation for children at highest risk.
BACKGROUND: • Extremely Low Birthweight (ELBW) neonates suffer later in life from adverse renal and cardiovascular outcomes. • Perinatal risk factors that further predict the individual risk for adverse outcomes are not well known.
BACKGROUND: • Poorer eGFR in adolescence was associated with male sex, longer ventilation and intra-ventricular hemorrhage at birth but not with blood pressure. • Former ELBW infants had higher blood pressures compared to controls, but no microalbuminuria. • This knowledge can lead to potential precision medicine, safer neonatal therapeutic regimens for ELBW infants, a more intensive follow-up and earlier treatment initiation for children at highest risk.

BACKGROUND: Nephron number variability may hold significance in the Developmental Origins of Health and Disease hypothesis. We explore the impact of gestational particulate pollution exposure on cord blood cystatin C, a marker for glomerular function, as an indicator for glomerular health at birth.
METHODS: From February 2010 onwards, the ENVIRONAGE cohort includes over 2200 mothers giving birth at the East-Limburg hospital in Genk, Belgium. Mothers without planned caesarean section who are able to fill out a Dutch questionnaire are eligible. Here, we evaluated cord blood cystatin C levels from 1484 mother-child pairs participating in the ENVIRONAGE cohort. We employed multiple linear regression models and distributed lag models to assess the association between cord blood cystatin C and gestational particulate air pollution exposure.
RESULTS: Average ± SD levels of cord blood cystatin C levels amounted to 2.16 ± 0.35 mg/L. Adjusting for covariates, every 0.5 μg/m³ and 5 μg/m³ increment in gestational exposure to black carbon (BC) and fine particulate matter (PM2.5) corresponded to increases of 0.04 mg/L (95% CI 0.01-0.07) and 0.07 mg/L (95% CI 0.03-0.11) in cord blood cystatin C levels (p < 0.01), respectively. Third-trimester exposure showed similar associations, with a 0.04 mg/L (95% CI 0.00-0.08) and 0.06 mg/L (95% CI 0.04-0.09) increase for BC and PM2.5 (p < 0.02). No significant associations were observed when considering only the first and second trimester exposure.
CONCLUSIONS: Our findings indicate that particulate air pollution during the entire pregnancy, with the strongest effect sizes from week 27 onwards, may affect newborn kidney function, with potential long-term implications for later health.
BACKGROUND: Special Research Fund (Bijzonder Onderzoeksfonds, BOF), Flemish Scientific Research Fund (Fonds Wetenschappelijk Onderzoek, FWO), and Methusalem.