Serum metabolomics reveals the effects of accompanying treatment on fatigue in patients with multiple myeloma.

PURPOSE: The renewal and iteration of chemotherapy drugs have resulted in more frequent long-term remissions for patients with multiple myeloma (MM). MM has transformed into a chronic illness for many patients, but the cancer-related fatigue (CRF) of many MM convalescent patients experience is frequently overlooked. We investigated whether the accompanying treatment of family members would affect MM patients' CRF and explore their serum metabolomics, so as to provide clinicians with new ideas for identifying and treating CRF of MM patients. METHODS: This was a single-center study, and a total of 30 MM patients were included in the study. Patients were divided into two groups based on whether they have close family members accompanying them through the whole hospitalization treatment. These patients received regular chemotherapy by hematology specialists, and long-term follow-up was done by general practitioners. Patients' CRF assessment for several factors used the Chinese version of the Brief Fatigue Inventory (BFI-C). Face-to-face questionnaires were administered at a time jointly determined by the patient and the investigator. All questionnaires were conducted by a general practitioner. The LC-MS-based metabolomics analysis determined whether the patients' serum metabolites were related to their fatigue severity. A correlation analysis investigated the relationship between serum metabolites and clinical laboratory indicators. RESULTS: The fatigue severity of MM patients whose family members participated in the treatment process (group A) was significantly lower than patients whose family members did not participate in the treatment process (group B). There was a statistically significant difference (fatigue severity composite score: t = - 2.729, p = 0.011; fatigue interference composite score: t = - 3.595, p = 0.001). There were no differences between the two groups of patients' gender, age, regarding clinical staging, tumor burden, blood routine, biochemical, or coagulation indexes. There were 11 metabolites, including guanidine acetic acid (GAA), 1-(Methylthio)-1-hexanethiol, isoeucyl-asparagine, L-agaritine, tryptophyl-tyrosine, and betaine, which significantly distinguished the two groups of MM patients. GAA had the strongest correlation with patient fatigue, and the difference was statistically significant (fatigue severity composite score: r = 0.505, p = 0.0044; fatigue interference composite score: r = 0.576, p = 0.0009). The results showed that GAA negatively correlated with albumin (r = - 0.4151, p = 0.0226) and GGT (r = - 0.3766, p = 0.0402). Meanwhile, GAA positively correlated with PT (r = 0.385, p = 0.0473), and the difference was statistically significant. CONCLUSION: The study is the first to report that family presence throughout the whole hospitalization may alleviate CRF in MM patients. Moreover, the study evaluated serum metabolites linked to CRF in MM patients and found that CRF has a significant positive correlation with GAA. GAA may be a more sensitive biomarker than liver enzymes, PT, and serum albumin in predicting patient fatigue. While our sample may not represent all MM patients, it proposes a new entry point to help clinicians better identify and treat CRF in MM patients.

Clinical significance of N-terminal natriuretic peptide combined with inflammatory factors, oxidative stress factors and blood lipid detection in elderly patients with Type-2 diabetes complicated with coronary heart disease.

Objectives: To observe the clinical significance of N-terminal natriuretic peptide combined with inflammatory factors, oxidative stress factors and blood lipid detection in elderly patients with Type-2 diabetes complicated with CHD (CHD), and provide a theoretical basis for the diagnosis and treatment of elderly patients with Type-2 diabetes complicated with CHD. Methods: A total of 40 patients with Type-2 diabetes complicated with CHD admitted to Affiliated Hospital of Hebei University from July 2019 and July 2020 were selected as the experimental group, and 40 patients with CHD who were hospitalized in our hospital during the same period without diabetes were selected as the control group. Venous blood was taken from all patients on morning and fasting basis, and their serum inflammatory factors as well as antioxidant molecules were examined respectively. Serum inflammatory factors include serum tumor necrosis factor α (TNF-A), interleukin-6 (IL-6), and C-reactive protein. Antioxidant molecules include antioxidant molecules superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (TAC), catalase (CAT), glutathione reductase (GR), N-terminal natriuretic peptide (NT-proBNP), white blood cells (WBC), hemoglobin (HBG), albumin (ALB) and blood lipid levels. The differences of the above indexes between experimental group and control group were compared and analyzed. Results: The serum levels of TNF-a, CRP, and IL-6 in the experimental group were apparently higher than those in the control group, with a statistically significant difference (P=0.00); The levels of SOD, TAC and CAT in the experimental group were significantly lower than those in the control group, with a statistically significant difference (P=0.00); The level of NT-proBNP and WBC count in the experimental group were significantly higher than those in the control group, with a statistically significant difference (NT-proBNP, P=0.01; WBC, P=0.00). However, no statistically significant difference was observed in the levels of HBG and ALB between the two groups (P>0.05). The experimental group had significantly higher TC and TG levels than the control group, with statistically significant differences (TC, P=0.01; TG, P=0.02), but had a significantly lower HDL level than the control group, with a statistically significant difference (P=0.00). Conclusion: Elderly patients with Type-2 diabetes complicated with CHD showed systemic microinflammation, decreased antioxidant molecule content, as well as myocardial damage and abnormal lipid metabolism compared with patients with CHD alone. For this reason, attention should be paid to the above risk factors in clinical practice, and proactive prevention and treatment should be taken to reduce the probability of related complications.

[3D Reconstruction of PCL Based on MRI and CT Image Fusion].

OBJECTIVE: To reconstruct three-dimensional (3D) image of posterior cruciate ligament (PCL) based on MRI and CT image fusion. METHODS: CT and MRI scans were performed on 12 knees of young men. The Dicom data were extracted and unified. The outline of PCL on MRI imaging was drew and plugged into the CT data. Finally, the visible 3D image of PCL with adjacent bones was reconstructed. The imaging anatomical measurements were examined and compared with those in published literature. RESULTS: Two cases were excluded from this study because of data deviations. The 3D visible reconstruction of PCL was proved to be feasible on the other ten cases. CONCLUSION: Three-dimensional visible reconstruction of PCL based on CT and MRI image fusion is feasible, which can provide support for individualized treatment of PCL injuries. Further simplification with increased accuracy may be needed.

Iterative dual energy material decomposition from spatial mismatched raw data sets.

Today's clinical dual energy computed tomography (DECT) scanners generally measure different rays for different energy spectra and acquire spatial mismatched raw data sets. The deficits in clinical DECT technologies suggest that mainly image based material decomposition methods are in use nowadays. However, the image based material decomposition is an approximate technique, and beam hardening artifacts remain in decomposition results. A recently developed image based iterative method for material decomposition from inconsistent rays (MDIR) can achieve much better image quality than the conventional image based methods. Inspired by the MDIR method, this paper proposes an iterative method to indirectly perform raw data based DECT even with completely mismatched raw data sets. The iterative process is initialized by density images that were obtained from an image based material decomposition. Then the density images are iteratively corrected by comparing the estimated polychromatic projections and the measured polychromatic projections. Only three iterations of the method are sufficient to greatly improve the qualitative and quantitative information in material density images. Compared with the MDIR method, the proposed method needs not to perform additional water precorrection. The advantages of the method are verified with numerical experiments from inconsistent noise free and noisy raw data.

[Expression and significance of neutrophil gelatinase-associated lipocalin in renal interstitial fibrosis in rats].

OBJECTIVE: To explore the expression and significance of neutrophil gelatinase-associated lipocalin(NGAL)in renal interstitial fibrosis (RIF) in rats. METHODS: A total of 60 male Sprague-Dawley rats were randomly divided into 3 groups of sham operation (SOR), unilateral ureteral obstruction (UUO) and angiotensin-converting enzyme inhibitor (ACEI). The serum concentrations of NGAL and tumor necrosis factor-alpha (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). And the expressions of NGAL, matrix metalloproteinase-9 (MMP-9) and transforming growth factor-ß1 (TGF-ß1) were observed by immunohistochemistry. RESULTS: (1) The levels of serum NGAL and TNF-α in UUO group obviously increased as compared to those in ACEI and SOR groups (NGAL: (69.2 ± 5.6) vs (41.0 ± 10.4), (10.8 ± 3.8) pg/ml; TNF-α: (116.2 ± 9.2) vs (99.8 ± 14.0), (29.2 ± 5.7) ng/ml; all P < 0.05). (2) The expressions of NGAL, TGF-ß1 and MMP-9 in renal tubular epithelial cells of UUO group increased as compared to those in SOR group. The expression of TGF-ß1 in ACEI group was apparently less than that in UUO group. The protein levels of NGAL and MMP-9 in ACEI group were obviously lower than those in UUO group within Day 14 post-operation and significantly higher than those in UUO group at Days 21 and 28. (3) In UUO group, the level of NGAL was positively correlated with the serum levels of TNF-α and serum creatinine (r = 0.910, 0.673, P < 0.01). The expression of NGAL had a highly positive correlation with MMP-9 (r = 0.913, P < 0.01) and the index of interstitial damage and the degrees of TGF-ß1 at Days 3-7 post-operation(r = 0.937, 0.847, P < 0.01). And the expression of NGAL was negatively correlated with the index of interstitial damage and the degrees of TGF-ß1 at Days 14-28 post-operation (r = -0.945, -0.944, P < 0.01). CONCLUSION: The expression of NGAL significantly increases in UUO modal of rats. And it is closely correlated with MMP-9, TNF-α and TGF-ß1. ACEI may influence the biological effects of NGAL by suppressing inflammatory responses, down-regulating the expression of TGF-ß1 and regulating the expression and the activity of MMP-9.

Serum Metabolomics Coupling With Clinical Laboratory Indicators Reveal Taxonomic Features of Leukemia.

Metabolic abnormality has been considered to be the seventh characteristic in cancer cells. The potential prospect of using serum biomarkers metabolites to differentiate ALL from AML remains unclear. The purpose of our study is to probe whether the differences in metabolomics are related to clinical laboratory-related indicators. We used LC-MS-based metabolomics analysis to study 50 peripheral blood samples of leukemia patients from a single center. Then Chi-square test and T test were used to analyze the clinical characteristics, laboratory indicators and cytokines of 50 patients with leukemia. Correlation analysis was used to explore the relationship between them and the differential metabolites of different types of leukemia. Our study shows that it is feasible to better identify serum metabolic differences in different types and states of leukemia by metabolomic analysis on existing clinical diagnostic techniques. The metabolism of choline and betaine may also be significantly related to the patient's blood lipid profile. The main enrichment pathways for distinguishing differential metabolites in different types of leukemia are amino acid metabolism and fatty acid metabolism. All these findings suggested that differential metabolites and lipid profiles might identify different types of leukemia based on existing clinical diagnostic techniques, and their rich metabolic pathways help us to better understand the physiological characteristics of leukemia.

[Size Distribution of Aerosol Hygroscopic Growth Factors in Winter in Tianjin].

Aerosol hygroscopic growth factors[g(RH)] are key for evaluating aerosol light extinction and direct radiative forcing. The hygroscopic tandem differential mobility analyzer (HTDMA) was utilized to measure the size-resolved gm(RH) under different polluted conditions in winter in Tianjin. Furthermore, based on the size distribution of aerosol water-soluble ions, the gκ(RH) across a wide size range (60 nm to 9.8 µm) was estimated using the κ-Köhler theory, which provides a basis for the estimation of aerosol optical parameters and direct radiative forcing under ambient conditions. Under clean conditions, ultrafine particles (<100 nm) were more hygroscopic and gm(RH=80%) was higher than 1.30 due to the active photolysis reaction. However, under severely polluted conditions, the proportion of water-soluble ions in aerosols increased with the increasing size; gm(RH) increased with particle size, where gm(RH=80%) and gm(RH=85%) for 300 nm particles was 1.39 and 1.46, respectively. For a wide size range (60 nm to 9.8 µm), the aerosols in the accumulation mode were more hygroscopic and aerosols in the Aitken mode were less hygroscopic, with coarse mode aerosols being the least hygroscopic. During the polluted period, the particulate size notably increased, and the mass fraction of NO3- and SO42- in the accumulation mode aerosols was significantly higher than during the clean period. Accordingly, the hygroscopicity of accumulation mode aerosols was strongly enhanced during the polluted period[gκ(RH)=1.3-1.4] and aerosols in the 0.18-3.1 µm size range all had a strong hygroscopicity. On polluted days, the synergistic effect of the increase in particle size, water-soluble ions, and aerosol hygroscopicity results in the considerable deterioration of visibility.

Olmesartan Medoxomil, An Angiotensin II-Receptor Blocker, Ameliorates Renal Injury In db/db Mice.

BACKGROUND: Diabetic nephropathy (DN) is a common complication of diabetes mellitus (DM) and also a major cause of end-stage renal disease (ESRD). Olmesartan medoxomil (OM) is an angiotensin II receptor blocker (ARB) and has been shown to exhibit renoprotective effects on a streptozotocin (STZ)-induced diabetic rat model. Yet, whether OM affects DN progression and renal injury in db/db mice, a type 2 diabetic murine model, has not been established. METHODS: Wild-type (n = 15) and db/db mice (n = 15) were treated with control saline or OM via oral gavage. The physiological and biochemical parameters were evaluated and histological examinations of kidney specimens were performed. RESULTS: Compared with saline-treated db/db mice, db/db mice administered with OM showed ameliorated diabetic physiological and biochemical parameters. In addition, OM decreased urinary albumin excretion and plasma creatinine level in db/db mice. Moreover, histologically, OM reduced glomerular hypertrophy and injury, and also ameliorated tubular injury, thus suggesting that OM improves renal function and minimizes renal pathological deterioration in db/db mice. CONCLUSION: Our study reveals a beneficial role of OM in ameliorating DN in db/db mice, which is associated with its renoprotective function.

[Spatial Temporal Characteristics and Cluster Analysis of Chemical Components for Ambient PM2.5 in Wuhan].

The characteristics of chemical components of particulate matter are good indicators for analyzing sources and causes of pollution. The spatial and temporal distribution characteristics of particulate matter can reflect regional pollution problems in urban development, providing a basic dataset to support effective control of particulate matter sources. We collected PM2.5 and analyzed its concentration and chemical components at eight sites during different seasons. The results indicated that the average concentration of PM2.5 in Wuhan reached 70.7 µg·m-3. The concentration of PM2.5 in winter (103.1 µg·m-3) was significantly higher than that of other seasons, and the lowest concentration was in autumn (52.4 µg·m-3). The concentrations of PM2.5 in Donghu Gaoxin, Zhuankou New Area, and Qingshan Ganghua Station were significantly higher than those at the other sites. The main chemical components in PM2.5 were OC and SO42-, accounting for 15.4% and 14.2%, respectively. The OC concentration was the highest in winter, whereas SO42-concentration was the highest in summer. The average annual OC/EC ratio was up to 2.80, lower in winter and spring, and higher in summer and autumn. Material reconstruction showed that secondary particles and organic matter (OM) were major substances, accounting for 32.34% and 20.44% of PM2.5 mass, respectively. Coal combustion and vehicle exhaust might be the main contributors to ambient PM2.5. The highest fractions for OM were at the Wujiashan and Donghu Gaoxin sites, whereas the fraction of secondary particles was higher at each site, suggesting that secondary pollution had obvious regional characteristics in Wuhan. Cluster analysis based on the characteristics of chemical components showed that the eight sites were divided into three clusters:1 Hanyang Yuehu, Haze, Donghu Liyuan, and Huangpi sites, where the main characteristics were that the concentrations of components at each point were low; ② Zhuankou New Area and Qingshan Ganghua, which were characterized by higher nitrogen components; and ③ Donghu Gaoxin and Wujiashan, where not only industrial sources were heavily polluted in Wuhan, but also motor vehicles and dust pollution greatly contributed.

Relationship between tumor and peripheral blood NPRL2 mRNA levels in patients with colorectal adenoma and colorectal cancer.

NPRL2 is a tumor suppressor gene involved in the progression of human cancer. The present study investigated whether NPRL2 expression correlates with colorectal cancer (CRC) progression. Colorectal tissue and peripheral blood samples were obtained from 62 patients with CRC, 38 patients with colorectal adenomas and 51 normal controls. NPRL2 mRNA levels in tissue samples and blood were measured using quantitative real-time PCR. NPRL2 protein expression was determined by immunohistochemistry. NPRL2 protein expression in CRCs was significantly lower than in the adenomas or normal colorectal tissue. NPRL2 mRNA expression was significantly decreased in adenomas compared with normal controls (P<0.0001) and it was further decreased in colorectal tumors compared with adenomas (P<0.0001). NPRL2 mRNA levels expression correlated with tumor stage. In addition, NPRL2 mRNA levels in the blood correlated with the levels detected in tumors. Furthermore, receiver operating characteristic (ROC) analysis showed that NPRL2 expression in blood could distinguish colorectal adenomas and CRCs from normal controls. NPRL2 mRNA expression in CRC tumor tissues and peripheral blood correlated with colorectal tumor progression. Based on our findings, we can conclude that NPRL2 mRNA blood levels could be a potentially useful marker for the detection of early stage adenomas and CRCs.