Abnormalities in the levels of calcium, phosphorus, and parathyroid hormone (PTH) in serum are typical for patients with chronic kidney disease (CKD). They are used routinely to predict the onset of CKD-mineral and bone disorder (MBD). However, CKD-MBD associated with metabolic pathway imbalance is not well understood.The objective of the study was to identify endogenous metabolic signatures in patients with intact PTH using mass spectrometry-based metabolomics. This study was a cross-sectional study. Ultra performance liquid chromatography-Quadrupole Time-of-Flight/mass spectrometry-based metabolic profiling was employed to analyze serum samples from 19 disease controls (DCs) (intact parathyroid hormone [iPTH] 150–300 pg/mL) and 19 secondary hyperparathyroidism (SHPT) patients (iPTH >300 pg/mL) (the training data set) to identify metabolic biomarkers for CKD-MBD. Then, another set of samples including 19 DCs (iPTH 150–300 pg/mL) and 19 SHPT patients (iPTH >300 pg/mL) (the test data set) were used to validate the potential biomarkers identified.Metabolic profiling analyses revealed different patterns of endogenous metabolites between the SHPT and the DC groups. A total of 32 unique metabolites were identified and 30 metabolites were elevated in the iPTH compared with control serum pools. Cytidine and l-phenylalanine were downregulated in the SHPT patients. The metabolic signatures identified were assessed respectively by an internal 10-fold cross validation with an accuracy of 91.4% and an external validation with an accuracy of 71.1%, a sensitivity of 73.7%, and a specificity of 68.4%.Mass spectrometry-based metabolomic analyses for SHPT patients promises immense potential for early diagnosis and therapy monitoring. Our results indicated that the onset of CKD-MBD is associated with pathway changes of protein synthesis and metabolism, amino acid metabolism, energy metabolism, and steroid hormone metabolism, with obvious promise for better understanding the pathogenesis of this disease. Several metabolic biomarkers were identified, which warrant further development.

Hyperlipidemia is considered to be a high lipid level in blood, can induce metabolic disorders and dysfunctions of the body, and results in some severe complications. Therefore, hunting for some metabolite markers and clarifying the metabolic pathways in vivo will be an important strategy in the treatment and prevention of hyperlipidemia. In this study, a rat model of hyperlipidemia was constructed according to histopathological data and biochemical parameters, and the metabolites of serum and urine were analyzed by UPLC-Q-TOF/MS. Combining pattern recognition and statistical analysis, 19 candidate biomarkers were screened and identified. These changed metabolites indicated that during the development and progression of hyperlipidemia, energy metabolism, lipid metabolism, amino acid metabolism and nucleotide metabolism were mainly disturbed, which are reported to be closely related to diabetes, cardiovascular diseases, etc. This study demonstrated that a UPLC-Q-TOF/MS based metabolomic approach is useful to profile the alternation of endogenous metabolites of hyperlipidemia.

This article presents a new perspective on the development of inorganic scintillator-based fiber dosimeters (IOSFDs) for medical radiotherapy dosimetry (RTD) focusing on real-time in vivo dosimetry. The scintillator-based optical fiber dosimeters (SFD) are compact, free of electromagnetic interference, radiation-resistant, and robust. They have shown great potential for real-time in vivo RTD. Compared with organic scintillators (OSs), inorganic scintillators (IOSs) have larger X-ray absorption and higher light output. Variable IOSs with maximum emission peaks in the red part of the spectrum offer convenient stem effect removal. This article outlines the main advantages and disadvantages of utilizing IOSs for SFD fabrication. IOSFDs with different configurations are presented, and their use for dosimetry in X-ray RT, brachytherapy (BT), proton therapy (PT), and boron neutron capture therapy (BNCT) is reviewed. Challenges including the percentage depth dose (PDD) deviation from the standard ion chamber (IC) measurement, the angular dependence, and the Cherenkov effect are discussed in detail; methods to overcome these problems are also presented.

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As one of the most troublesome complications in patients with chronic renal disease, the etiology of uremic pruritus remains unknown, and the current therapeutic approaches are limited and unsatisfactory. To identify potential biomarkers for improving diagnosis and treatment and obtain a better understanding of the pathogenesis of uremic pruritus, we compared serum metabolome profiles of severe uremic pruritus (HUP) patients with mild uremic pruritus (LUP) patients using ultraperformance liquid chromatography-quadruple time-of-flight mass spectrometry (UPLC-QTOF MS). Partial least squares discriminant analysis (PLS-DA) showed that the metabolic profiles of HUP patients are distinguishable from those of LUP patients. Combining multivariate with univariate analysis, 22 significantly different metabolites between HUP and LUP patients were identified. Nine of the 22 metabolites in combination were characterized by a maximum area-under-receiver operating characteristic curve (AUC = 0.899) with a sensitivity of 85.1% and a specificity of 83.0% distinguishing HUP and LUP. Our results indicate that serum metabolome profiling might serve as a promising approach for the diagnosis of uremic pruritus and that the identified biomarkers may improve the understanding of pathophysiology of this disorder. Because the 9 metabolites were phospholipids, uremic toxins, and steroids, further studies may reveal their possible role in the pathogenesis of uremic pruritus.

Anemia is an almost universal complication of chronic kidney disease (CKD), and nearly all patients with endstage renal disease (ESRD) and approximately 70% of those with earlier stages of CKD receive treatment for anemia. Due to its significance in the treatment of anemia, there is increased reliance on iron in the renal anemia population. In clinical practice, not every patient benefits from intravenous (IV) iron therapy. In order to identify patients who will respond to IV iron therapy and who will not respond to it, our goals were to identify the potential serum biomarkers that could predict the response to IV iron therapy in renal anemia patients. The metabolic profiles of serum from 41 renal anemia patients with complete, partial or non-response to IV iron therapy were studied using a combination of liquid chromatography coupled with mass spectrometry (LC-MS) and multivariate analysis methods to identify the potential biomarkers that could predict the response to IV iron therapy in renal anemia patients. Oleamide and ascorbate 2-sulfate (AS) were identified and verified as the potential biomarkers. A prediction model constructed with oleamide and AS correctly identified approximately 83.3% of patients who were non-responsive to IV iron therapy and 87.5% of patients who had a complete response to IV iron therapy. The model has excellent discriminant performance, with an AUC of 0.901. These results show promise for larger studies that could advance more personalized treatment protocols for renal anemia patients.

Hypertension is a common chronic disease, and it is the strongest risk factor for cardiovascular disease. Recently, the number of patients with hypertension-related complications has increased significantly, adding a heavy burden to the public health system. It is known that chronic stress plays an important role in the pathogenesis of cardiovascular diseases such as hypertension and stroke. However, the impact of hypertension on the dysfunctions induced by chronic stress remains poorly understood. In this study, using LC-MS-based metabolomics, we established a chronic stress model to demonstrate the mechanisms of stress-induced hypertension. We found that 30 metabolites in chronically stressed rats were changed; of these metabolites, seven had been upregulated, and 23 had been downregulated, including amino acids, phospholipids, carnitines and fatty acids, many of which are involved in amino acid metabolism, cell membrane injury, ATP supply and inflammation. These metabolites are engaged in dysregulated pathways and will provide a targeted approach to study the mechanism of stress-induced hypertension.

Chronic stress, a leading factor for high blood pressure (BP) and even hypertension, affects health quality seriously. However, the management is rather difficult in our rapidly developing modern society, and...