Biomarker is the measurable change associated with a physiological or pathophysiolog-ical process. Unlike blood which has mechanisms to keep the internal environment homeostatic, urine is more likely to reflect changes of the body. As a result, urine is likely to be a better biomarker source than blood. However, since the urinary proteome is affected by many factors, including diuretics, careful evaluation of those effects is necessary if urinary proteomics is used for biomarker discovery. Here, we evaluated the effects of three commonly-used diuretics (furosemide, F;hydro-chlorothiazide, H; and spirolactone, S) on the urinary proteome in rats. Urine samples were col-lected before and after intragastric administration of diuretics at therapeutic doses and the proteomes were analyzed using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS). Based on the criteria of P 6 0.05, a fold change P2, a spectral count P5, and false positive rate (FDR) 61%, 14 proteins (seven for F, five for H, and two for S) were identified by Progenesis LC-MS. The human orthologs of most of these 14 proteins are stable in the healthy human urinary proteome, and ten of them are reported as disease biomarkers. Thus, our results suggest that the effects of diuretics deserve more attention in future urinary protein biomarker studies. Moreover, the distinct effects of diuretics on the urinary proteome may provide clues to the mechanisms of diuretics.

Objective To investigate serum vitamin D levels in middle-aged and elderly patients with diabetes mellitus (DM) only,hypertension only,dyslipidemia only,or a combination of these conditions.Methods We consecutively recruited patients aged 45 years or over with DM only (n=100),hypertension only (n=100),dyslipidemia only (n=100),and a combination of these three conditions (n=100) from Beijing Hospital and further included 100 healthy individuals aged 45 or over undergoing routine physical examinations to serve as the control group.Fasting venous blood was collected and analyzed with an automated biochemical analyzer for glucose (GLU),total cholesterol (TC),triglycerides (TG),high-density lipoprotein cholesterol (HDL-C),and low-density lipoprotein cholesterol (LDL-C);Vitamin D,in the form of 25 hydroxycholecalciferol (25[OH]D),was measured using an electrochemiluminescence (ECLIA) method;HbA1c was detected using cation exchange high performance liquid chromatography.Results There were significant differences in serum vitamin D levels between the four noncontrol groups[DM:(16.9±7.3) μg/L,hypertension:(16.4±7.5) μg/L,dyslipidemia:(15.3±6.9) μg/L,and the combination group (15.2±7.1) μg/L]and the control group [(21.0±7.5) μg/L](all P＜0.01),but no significant difference was found in vitamin D levels among the four noncontrol groups (all P ＞0.05).When subjects were classified as vitamin D sufficient (≥ 30.0 μg/L),insufficient (20.0-29.9μg/L),deficient (10.0-19.9 μg/L) and severely deficient (＜10.0 μg/L),the proportions of severely deficient and deficient subjects in the four diseased groups were higher than in the control group,and the highest proportion was found in the combination group.Compared with the four diseased groups,the control group showed the highest proportion of subjects with insufficient vitamin D.The control group had the highest proportion with sufficient vitamin D,whereas the combination group had the lowest.Conclusions Serum vitamin D levels in patients with DM,hypertension or dyslipidemia,or a combination of these conditions are significantly lower than in normal individuals.Attention should be paid to vitamin D levels and their alterations in these patients.

Objective To investigate serum levels of lipoprotein-associated phospholipase A2 (Lp-PLA2),high-sensitivity C-reactive protein (hs-CRP),complement component C1q (C1q) and homocysteine(HCY) in patients with Alzheimer's disease(AD),in order to provide a basis for establishing laboratory markers in AD patients.Methods One hundred AD patients and one hundred healthy controls from Beijing Hospital were selected.Serum levels of Lp-PLA2,C1q,hs-CRP and HCY were determined using a biochemistry analyzer.Serum levels of amyloid β-protein 40(Aβ40)and Aβ42 were measured using enzyme-linked immunosorbent assays.Results Serum levels of Aβ40,Aβ42,Lp-PLA2,hs-CRP,C1 q and HCY were higher in AD patients than in the control group[(66.0±14.0) pmol/L vs.(7.1±8.2) pmol/L,(7.2±1.4) pmol/L vs.(1.9±1.7) pmol/L,(510.6±140.1)U/L vs.(419.0±91.8) U/L,(2.8±3.4) mg/L vs.(1.2±0.7) mg/L,(218.0±58.4) mg/L vs.(194.8 ± 27.7) mg/L and (18.8 ± 9.3) μmol/L vs.(14.9 ± 5.2) μmol/L,all P ＜ 0.01],and the differences were greater in female subjects than in male subjectss.Conclusions High serum levels of Lp-PLA2,C1q,hs-CRP and HCY may be associated with Alzheimer's disease,while the exact relationships need to be further investigated.

To analyze the changes in lactate dehydrogenase, creatine kinase, creatine kinase isoenzyme, high-sensitivity troponin T, N-terminal B-type natriuretic peptide precursor, homocysteine, and novel inflammatory indices (neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, systemic immune-inflammation index) before and after competitions in amateur marathon runners, and to assess the effects of myocardial injury due to acute exercise and the value of novel inflammatory indices in marathon exercise monitoring. This paper is an analytical study. Amateur athletes recruited by Beijing Hospital to participate in the 2022 Beijing Marathon and the 2023 Tianjin Marathon, and those who underwent health checkups at the Beijing Hospital Medical Checkup Center from January to June 2023 were selected as the study subjects, and 65 amateur marathon runners (41 males and 24 females) and 130 healthy controls (82 males and 48 females) were enrolled in the study according to the inclusion criteria. Peripheral blood was collected one week before, immediately after, and one week after running, and routine blood tests, cardiac enzymes, infarction markers, N-terminal B-type natriuretic peptide precursor, and homocysteine were performed to calculate the values of novel inflammatory indexes. Wilcoxon signed-rank test and Spearman′s rank correlation analysis were used to compare the differences in the levels of each index between the amateur marathon population and the health checkup population, and to compare the changes and correlations of each index at the three time points in the amateur marathoners.The results showed that the neutrophil-lymphocyte ratios of the healthy physical examination population and 65 amateur marathoners 1 week before running were 1.73 (1.33, 2.16) and 1.67 (1.21, 2.16), the platelet-lymphocyte ratios were 122.75 (96.69, 155.89) and 120.86 (100.74, 154.63), and the systemic immune inflammation index was 398.62 (274.50, 538.69) and 338.41 (258.62, 485.38), etc.; on 1 week before running, immediately after running and 1 week after running, lactate dehydrogenase of 65 amateur marathon runners was 173.00(159.00, 196.50)U/L,284.00(237.50, 310.50)U/L, 183.00(165.50, 206.50)U/L, creatine kinase was 131.00(94.30, 188.20)U/L,318.00(212.00, 573.15)U/L,139.00(90.55, 202.40)U/L, creatine kinase isoenzyme was 2.50(1.76, 3.43)μg/L,6.24(4.87, 10.30)μg/L,2.73(1.57, 4.40)μg/L.In 65 amateur marathon runners, lactate dehydrogenase, creatine kinase, creatine kinase isoenzyme, high sensitivity troponin T, N-terminal B-type natriuretic peptide precursor, homocysteine, and novel inflammation markers were significantly elevated in the immediate post-run period compared with 1 week before the run, and the differences were statistically significant ( Z=-7.009, Z=-6.813, Z=-6.885, Z=-7.009, Z=-7.009, Z=-6.656; P<0.05 for the above indicators).Neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and systemic immune-inflammatory index all showed significant positive correlation with the pre-and post-run rates of change of high-sensitivity troponin T ( ρ=0.28, P=0.03; ρ=0.31, P=0.01; ρ=0.27, P=0.03); these 3 markers were also significantly and positively correlated with the pre-and post-run rates of change in a collection of myocardial-related markers such as lactate dehydrogenase, creatine kinase, creatine kinase isozymes, high-sensitivity troponin T, N-terminal B-type natriuretic peptide precursor, and homocysteine, respectively( r=0.446, P=0.039; r=0.452, P=0.033; r=0.449, P=0.036).In addition, the platelet-lymphocyte ratio was positively correlated with the pre-and post-run rates of change in creatine kinase and creatine kinase isoenzymes( ρ=0.27, P=0.03; ρ=0.28, P=0.02).In conclusion, acute myocardial injury may be triggered during marathon exercise. Changes in novel inflammatory markers were significantly associated with changes in myocardial enzymes, infarction markers, N-terminal B-type natriuretic peptide precursors, and homocysteine, which may be of value for the prediction of myocardial injury during exercise.

To analyze the changes in lactate dehydrogenase, creatine kinase, creatine kinase isoenzyme, high-sensitivity troponin T, N-terminal B-type natriuretic peptide precursor, homocysteine, and novel inflammatory indices (neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, systemic immune-inflammation index) before and after competitions in amateur marathon runners, and to assess the effects of myocardial injury due to acute exercise and the value of novel inflammatory indices in marathon exercise monitoring. This paper is an analytical study. Amateur athletes recruited by Beijing Hospital to participate in the 2022 Beijing Marathon and the 2023 Tianjin Marathon, and those who underwent health checkups at the Beijing Hospital Medical Checkup Center from January to June 2023 were selected as the study subjects, and 65 amateur marathon runners (41 males and 24 females) and 130 healthy controls (82 males and 48 females) were enrolled in the study according to the inclusion criteria. Peripheral blood was collected one week before, immediately after, and one week after running, and routine blood tests, cardiac enzymes, infarction markers, N-terminal B-type natriuretic peptide precursor, and homocysteine were performed to calculate the values of novel inflammatory indexes. Wilcoxon signed-rank test and Spearman′s rank correlation analysis were used to compare the differences in the levels of each index between the amateur marathon population and the health checkup population, and to compare the changes and correlations of each index at the three time points in the amateur marathoners.The results showed that the neutrophil-lymphocyte ratios of the healthy physical examination population and 65 amateur marathoners 1 week before running were 1.73 (1.33, 2.16) and 1.67 (1.21, 2.16), the platelet-lymphocyte ratios were 122.75 (96.69, 155.89) and 120.86 (100.74, 154.63), and the systemic immune inflammation index was 398.62 (274.50, 538.69) and 338.41 (258.62, 485.38), etc.; on 1 week before running, immediately after running and 1 week after running, lactate dehydrogenase of 65 amateur marathon runners was 173.00(159.00, 196.50)U/L,284.00(237.50, 310.50)U/L, 183.00(165.50, 206.50)U/L, creatine kinase was 131.00(94.30, 188.20)U/L,318.00(212.00, 573.15)U/L,139.00(90.55, 202.40)U/L, creatine kinase isoenzyme was 2.50(1.76, 3.43)μg/L,6.24(4.87, 10.30)μg/L,2.73(1.57, 4.40)μg/L.In 65 amateur marathon runners, lactate dehydrogenase, creatine kinase, creatine kinase isoenzyme, high sensitivity troponin T, N-terminal B-type natriuretic peptide precursor, homocysteine, and novel inflammation markers were significantly elevated in the immediate post-run period compared with 1 week before the run, and the differences were statistically significant ( Z=-7.009, Z=-6.813, Z=-6.885, Z=-7.009, Z=-7.009, Z=-6.656; P<0.05 for the above indicators).Neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and systemic immune-inflammatory index all showed significant positive correlation with the pre-and post-run rates of change of high-sensitivity troponin T ( ρ=0.28, P=0.03; ρ=0.31, P=0.01; ρ=0.27, P=0.03); these 3 markers were also significantly and positively correlated with the pre-and post-run rates of change in a collection of myocardial-related markers such as lactate dehydrogenase, creatine kinase, creatine kinase isozymes, high-sensitivity troponin T, N-terminal B-type natriuretic peptide precursor, and homocysteine, respectively( r=0.446, P=0.039; r=0.452, P=0.033; r=0.449, P=0.036).In addition, the platelet-lymphocyte ratio was positively correlated with the pre-and post-run rates of change in creatine kinase and creatine kinase isoenzymes( ρ=0.27, P=0.03; ρ=0.28, P=0.02).In conclusion, acute myocardial injury may be triggered during marathon exercise. Changes in novel inflammatory markers were significantly associated with changes in myocardial enzymes, infarction markers, N-terminal B-type natriuretic peptide precursors, and homocysteine, which may be of value for the prediction of myocardial injury during exercise.