Procollagen Amino-terminal Peptide Research Articles

Anti-osteoporosis effect of Prunus humilis fruit on ovariectomized rats via modulating the function of bone metabolism

Prunus humilis Bge. (PH), also known as calcium fruits, is rich in minerals and polyphenols. Given its high content of calcium and other mineral elements, it is believed to be an ideal health fruit to prevent osteoporosis (OP). Hence, the present research aimed to estimate the anti-osteoporotic activity of the fruit of PH in ovariectomized (OVX) rats and to explore the corresponding mechanisms. By utilizing LC-QTOF-MS/MS, 18 primary components, including 14 flavonoids and 4 phospholipids were elucidated in PH. The results of inductively coupled plasma optical emission spectrometry demonstrated that PH exhibited high levels of calcium (1573–1829 mg/kg), phosphorus (1328–1731 mg/kg), and magnesium (897–1027 mg/kg). The pharmacodynamic experiments conducted on OVX rats revealed that continuous oral intervention with PH (10–62.5 mg/kg/day) for three months resulted in significant improvements in both bone mineral density and bone microarchitecture. Meanwhile, the intervention with PH also effectively reversed the bone resorption and formation factors, including type I collagen carboxy-terminal peptide, acid phosphatase 5 tartrate-resistant, deoxypyridinoline, alkaline phosphatase, and procollagen amino-terminal peptide. Additionally, the utilization of LC-QTOF-MS/MS metabolomics revealed the identification of 16 differential metabolites linked to 9 metabolic pathways, all of which were recovered following PH treatment. Furthermore, the protein levels of β-catenin, Wnt1, Sirt1, and FOXO3a were significantly up-regulated after PH intervention, indicating a potential association between the anti-osteoporosis properties of PH and the Wnt/β-catenin and Sirt1/FOXO3a signaling pathways. Our findings provide a new idea for the prevention and treatment of OP through the daily consumption of PH, a sweet and flavorful fruit.

Analysis of changes in serum high t-PINP/β-CTX ratio and risk of re-fracture after vertebral osteoporotic fracture surgery.

This study's aim was to investigate the expression changes of total type I procollagen amino-terminal peptide (t-PINP) and type I collagen C-terminal peptide (β-CTX) in serum after vertebral osteoporotic fracture surgery and the clinical value of predicting the risk of refracture. The clinical data of 100 patients with vertebral osteoporotic fractures treated in our hospital from January 2019 to January 2020 were retrospectively analyzed, and the patients were divided into the control group (patients without re-fracture, n = 68) and the observation group (patients with re-fracture, n = 32) according to whether they had re-fracture at 2-year follow-up. The risk factors of postoperative re-fracture were analyzed using Multivariate logistic regression analysis. The serum contents of t-PINP, β-CTX, osteocalcin (BGP), and calcium (Ca) were measured. Bone mineral density (BMD) was measured by bone densitometer. The correlation between the t-PINP/β-CTX ratio and the bone metabolic index was analyzed by Pearson correlation. The area under the curve (AUC), sensitivity, and specificity of t-PINP/β-CTX in predicting the risk of re-fracture were determined by the receiver operating characteristic (ROC) curve. There was a significant difference in age, the number of vertebral bodies with initial fracture, and whether there was leakage of bone cement between the two groups (p < 0.05). Age, the number of vertebral bodies with primary fracture, and the leakage of bone cement were risk factors affecting re-fracture after operation (p < 0.05). Compared with those in the control group, the level of t-PINP and the ratio of t-PINP/β-CTX were higher, and the β-CTX level was lower in the observation group (p < 0.05). The BGP level was higher, and the levels of BMD and Ca were lower in the observation group than those in the control group (p < 0.05). Pearson correlation analysis showed that t-PINP had a positive correlation with BGP (r = 0.222, p < 0.05). β-CTX was positively correlated with BMD and Ca (r = 0.230, 0.269, p < 0.05). The ratio of t-PINP/ β-CTX was negatively correlated with BMD and Ca (r = -0.621 and -0.660, p < 0.05), but positively correlated with BGP (r = 0.517, p < 0.05). ROC curve analysis showed that the AUC of t-PINP, β-CTX, and the ratio of t-PINP/β-CTX in predicting the risk of re-fracture after vertebral osteoporotic fracture surgery was 0.724, 0.736, and 0.838, respectively. The t-PINP/β-CTX ratio was significantly correlated with the bone metabolic indexes in patients with vertebral osteoporotic fractures. The detection of the changes in its index can help predict the risk of postoperative re-fracture, providing a new idea for clinical assessment of the risk of postoperative re-fracture.

The relationship between coronary artery calcification and bone metabolic markers in maintenance hemodialysis patients

BackgroundTo study the influencing factors for coronary artery calcification (CAC) in maintenance hemodialysis (MHD) patients and the relationship between CAC and bone metabolism markers and to attempt to find a reliable marker linking vascular calcification and bone metabolism in MHD patients.MethodsA total of 123 patients were enrolled. CAC was assessed by multislice spiral computed tomography (MSCT), and the CAC score (CACS) was evaluated using the Agaston method. Routine laboratory parameters, including triglycerides (TG), total cholesterol (TC), glucose (Glu), calcium (Ca), phosphorus (P), magnesium (Mg), etc., were measured. Serum markers of bone metabolism, such as alkaline phosphatase(ALP), calcitonin (CT), 25-hydroxy vitamin D [25-(OH)D], intact parathyroid hormone (iPTH), total type I procollagen amino-terminal peptide (tPINP), N-terminal mid-fragment of osteocalcin (N-MID OC), and β-type I collagen crosslinked carboxyl-terminal peptide (β-CTX), were also measured.ResultsAmong 123 MHD patients, 37 patients (30.08%) did not have CAC, and 86 patients (69.92%) had CAC, including 41 patients (47.67%) with mild calcification and 45 patients (52.33%) with moderate to severe calcification. Age, Body Mass Index(BMI), the prevalence of hypertension and diabetes mellitus, TC, Glu, P, and Ca×P in the calcification group were higher than those in the noncalcification group, whereas Mg, iPTH, tPINP, N-MID OC, and β-CTX were lower than those in the noncalcified group (P < 0.05). Compared with the mild calcification group (0<CACS<400), P and Ca×P levels were higher in the moderate to severe calcification group (CACS ≥ 400), and ALP, iPTH, N-MID OC, tPINP, and β-CTX concentrations were lower (P < 0.05). Correlation analysis showed that the CACS was positively correlated with TC, LDL-C, P, and Ca×P (P < 0.05) and negatively correlated with N-MID OC and β-CTX (P < 0.05). There was no significant correlation between the CACS and other parameters (P > 0.05). A logistic regression model was used to evaluate the influencing factors for CAC. The results showed that age, BMI, TC, Glu, P, and Ca×P were risk factors for CAC and its severity in MHD patients, whereas diabetes mellitus, Mg, and N-MID OC were protective factors for CAC in MHD patients. In addition, N-MID OC was a protective factor for the severity of CAC. After adjusting for the corresponding confounding factors, the results of the risk factors were consistent, and N-MID OC was still an independent protective factor for CAC and its severity.ConclusionsElevated serum P and Ca×P were independent risk factors for CAC in MHD patients, and serum Mg may be an independent protective factor for CAC. CAC was closely related to abnormal bone metabolism and bone metabolic markers in MHD patients. Relatively low bone turnover can promote the occurrence and development of CAC. N-MID OC may be a reliable bone metabolic marker linking vascular calcification and bone metabolism in MHD patients.

Effects of vitamin K supplementation on reproductive performance and bone metabolism-related biochemical markers in lactation sows.

This study was conducted to evaluate the effects of vitamin K (VK) supplementation on reproductive performance and bone metabolism-related biochemical markers in sows. Twenty-four Large White×Landrace sows (mean parity 4.04) were randomly assigned to two dietary treatments (NC diet, a basal diet with 0.5 mg/kg of VK3; VK diet, a basal diet with 5 mg/kg of VK3) with twelve replicates per treatment and one sow per replicate according to parity. The experiment started on day 107 of gestation and lasted until day 21 of lactation (weaning). We observed that there were no differences (p>0.05) in average daily feed intake, backfat loss of sows, live piglet number at birth and weaning, average birth weight, average weaning weight, and average daily gain of piglets between two treatments. The apparent total tract digestibility of phosphorus was increased (p<0.05) in VK sows compared with NC sows. The serum bone alkaline phosphatase, osteocalcin, type I procollagen aminoterminal peptide, and type I procollagen carboxyl-terminal peptide on day of farrowing were higher (p<0.05) in VK sows than in NC sows. The serum phosphorus, parathyroid hormone, tartrate-resistant acid phosphatase, and tumor necrosis factor-alpha on day of weaning were lower (p<0.05) in VK sows compared with NC sows. Therefore, the overall results suggested that increasing dietary VK3 (0.5 to 5 mg/kg) during lactation improved the apparent total tract digestibility of phosphorus and serum bone metabolism biochemical markers in sows.

Vitamin D inhibits bone loss in mice with thyrotoxicosis by activating the OPG/RANKL and Wnt/β-catenin signaling pathways.

Vitamin D and thyroid hormones have crucial roles in bone metabolism. This study aims to explore the effects of vitamin D on bone metabolism in mice with thyrotoxicosis and its mechanisms. 12-week-old mice were randomly divided into 6 groups (6 mice/group), the control (CON) group, vitamin D (VD) group, low-dose LT4 (Low LT4) group, low-dose LT4+VD (Low LT4+VD) group, high-dose LT4 (High LT4) group, high-dose LT4+VD (High LT4+VD) group, LT4 was provided every day and vitamin D3 every other day for 12 weeks. Thyroid function, 25-hydroxy vitamin D, type I collagen carboxy-terminal peptide (CTX), and type I procollagen amino-terminal peptide were determined. In addition, microcomputed tomography, bone histology and histomorphometry, a three-point bending test, and the mRNA expression of osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL) and β-catenin in bone were conducted. The BMD of lumbar vertebrae and femur decreased and the bone microstructure was destroyed significantly in thyrotoxicosis mice. Addition of vitamin D improved the BMD and bone microstructure only in the low LT4+VD group. Mice with thyrotoxicosis had a significantly higher level of CTX (P<0.05), which was decreased by treatment with vitamin D (P<0.05). The eroded surface per bone surface (Er. S/BS) of the cancellous bone and elongated surface/endocortical perimeter (Er. S/E Pm) of the cortical bone significantly increased in the Low LT4 and High LT4 groups (P<0.05). Treatment with vitamin D significantly decreased the Er. S/BS and Er. S/E Pm. But, treatment with vitamin D did not significantly improve the toughness and rigidity of bones. The ratio of OPG to RANKL and mRNA expression of β-catenin in the Low LT4+VD group were higher than that in the Low LT4 group (P<0.05). In mice with thyrotoxicosis, treatment with vitamin D can inhibit bone resorption and improve the BMD and trabecular bone architecture by increasing the ratio of OPG to RANKL and upregulating the expression of Wnt/β-catenin.

Serum vitamin K2 level and its association with bone metabolism markers in 1 732 children

To study the level of serum vitamin K2 (VitK2) and its association with bone metabolism markers osteocalcin (OC), type I procollagen amino-terminal peptide (PINP), and type I collagen carboxy-terminal peptide (CTX) in children. A prospective analysis was performed on 1 732 children who underwent routine physical examination from October 2020 to October 2021. The serum levels of VitK2 and 25-hydroxy vitamin D [25(OH)D] were measured. According to age, they were divided into four groups: <1 year, 1-3 years group, >3-6 years group, and >6-14 years. A total of 309 children with 25(OH)D≥50 nmol/L were screened out, and serum levels of OC, PINP, and CTX were measured to investigate the correlation of the serum levels of OC, PINP, and CTX with serum VitK2 levels in different age groups. The prevalence rate of serum VitK2 deficiency was 52.31% (906/1 732). The VitK2 deficiency group had higher prevalence rates of overweight/obesity and growth pain (≥3 years of age) than the normal VitK2 group (P<0.05). There were differences in the prevalence rate of serum VitK2 deficiency (P<0.0083) and the serum level of VitK2 (P<0.05) between the 1-3 years group and the >6-14 years group. The <1 year group had a higher serum level of CTX and a lower serum level of PINP than the >3-6 years group and the >6-14 years group (P<0.05). The <1 year group had a lower serum level of OC than the >6-14 years group (P<0.05). Serum VitK2 level was positively correlated with OC level (rs=0.347, P<0.01), and CTX level was negatively correlated with PINP level (rs=-0.317, P<0.01). Serum VitK2 deficiency may be associated with overweight/obesity. Serum VitK2 may affect the level of OC and even bone health.

The relationship between estimated glucose disposal rate and bone turnover markers in type 2 diabetes mellitus.

To investigate the relationship between estimated glucose disposal rate (eGDR) and bone turnover markers in patients with type 2 diabetes mellitus (T2DM). This is a cross-sectional study, which recruited 549 patients with T2DM. The eGDRs of patients were calculated based on the presence of hypertension, glycated hemoglobin, and body mass index. All patients were divided into high-eGDR group and low-eGDR group using the median of eGDR as the boundary. The patients were further divided into two subgroups: males and postmenopausal females. The lower the eGDR, the more severe was insulin resistance. The levels of osteocalcin (OC), type I collagen carboxyl-terminal peptide (β-CTX), and type I procollagen amino-terminal peptide (PINP) were significantly lower in the low-eGDR group than those in the high-eGDR group. The eGDR was positively correlated with OC, β-CTX, and PINP in all patients, and in the male subgroups. In the postmenopausal female subgroup, there was no correlation between eGDR and OC, β-CTX, or PINP. In addition, this positive correlation remained after adjusting for other factors in multilinear regression analysis. Our study was the first to demonstrate that eGDR is positively correlated with bone turnover markers in patients with T2DM. This correlation was observed among the male patients with T2DM but not among postmenopausal female patients with T2DM.

Influence of Obesity on Bone Turnover Markers and Fracture Risk in Postmenopausal Women.

Background and aims: The relationship between obesity and bone metabolism is controversial. In recent decades, the protective role of obesity in the development of osteoporosis is questioned. The aims of this study are the following: to evaluate the differences in bone turnover markers between postmenopausal women with and without obesity and to compare the risk of fracture at five years between these groups. Methods: An observational longitudinal prospective cohort study of postmenopausal women with obesity (O) (body mass index (BMI) > 30 kg/m2) and non-obesity (NoO) (BMI < 30 kg/m2) is designed. 250 postmenopausal women are included in the study (NoO: 124 (49.6%) and O: 126 (50.4%)). It measures epidemiological variables, dietary variables (calcium intake, vitamin D intake, smoking, alcohol consumption, and physical activity), biochemicals (β-crosslap, type I procollagen amino-terminal peptide (P1NP), 25OH-vitamin D, and parathyroid hormone (PTH)), anthropometric variables, and fracture data five years after the start of the study. The mean age is 56.17 (3.91) years. Women with obesity showed lower levels of vitamin D (O: 17.27 (7.85) ng/mL, NoO: 24.51 (9.60) ng/mL; p < 0.01), and higher levels of PTH (O: 53.24 (38.44–65.96) pg/mL, NoO: 35.24 (25.36–42.40) pg/mL; p < 0.01). Regarding the bone formation marker (P1NP), it was found to be high in women without obesity, O: 45.46 (34.39–55.16) ng/mL, NoO: 56.74 (45.34–70.74) ng/mL; p < 0.01; the bone resorption marker (β-crosslap) was found to be high in women with obesity, being significant in those older than 59 years (O: 0.39 (0.14) ng/mL, NoO 0.24 (0.09) ng/mL; p < 0.05). No differences are observed in the risk of fracture at 5 years based on BMI (OR = 0.90 (95%CI 0.30–2.72); p = 0.85). Conclusions: Postmenopausal women with obesity showed lower levels of bone formation markers; older women with obesity showed higher markers of bone resorption.

Rapamycin activates autophagy by inhibiting mTOR pathway to alleviate early osteoporosis in rats with skeletal fluorosis

Objective: To investigate the effects of rapamycin target protein (mTOR) pathway and autophagy on bone formation and bone resorption in fluorosis osteoporosis in rats. Methods: In September 2018, a rat model of skeletal fluorosis was established by intragastric administration of fluorine. The experimental animals were divided into control group, 10 mgF(-)/kg group, 20 mgF(-)/kg group, 2 mg/kg rapamycin (RAPA) +10 mgF(-)/kg group and 2 mg/kg RAPA+20 mgF(-)/kg group, 20 per group. The experiment lasted for 3 months. The changes of bone tissue in rats were observed by hematoxylin-eosin (HE) staining. Bone mineral density (BMD) and biomechanical indexes, such as Modulus of elasticity, Stiffness, Maximum stress and Maximum load, were measured by BMD and biomechanical biometer. Serum levels of alkaline phosphatase (ALP) , osteocalcin (BGP) , osteoprotectin (OPG) , type I procollagen amino-terminal peptide (PINP) , tartrate-resistant acid phosphatase (TRACP) and nuclear factor kappa B receptor activator ligand (RANKL) were determined by enzymatic linked immunosorbent assay (ELISA) . Bone tissue phosphorylated mTOR (p-mTOR) , autophagy-related index selective autophagy adaptor protein p62, microtubule associated protein II (LC3-II) , ALP, osteoblastic transcription factor (Osterix) , and RNT Expression of related transcription factor 2 (Runx2) and bone resorption indicator RANKL were detected by Western blotting. Results: Compared with the control group, dental fluorosis in the 10 mgF(-)/kg and 20 mgF(-)/kg groups was significantly increased, periosteum thickness and absorption lacunae appeared, and BGP, OPG, PINP, TRACP and RANKL in serum contents were increased (P<0.05) , BMD, Modulus of elasticity, Stiffness, Maximum stress and Maximum load of bone tissue decreased significantly (P<0.05) , and the expressions of p-mTOR and p62 were decreased (P<0.05) , also the expressions of ALP, Osterix, Runx2 and RANKL were increased (P<0.05) . Compared with 10 mgF(-)/kg and 20 mgF(-)/kg groups, there were no obvious dental fluorosis symptoms in 2 mg/kg RAPA+10 mgF(-)/kg group and 2 mg/kg RAPA+20 mgF(-)/kg group, and serum ALP, BGP and OPG levels were significantly increased (P<0.05) . TRACP and RANKL contents were significantly decreased (P<0.05) . BMD, Modulus of elasticity, Stiffness, Maximum stress and Maximum load were significantly increased (P<0.05) . The levels of p-mTOR, p62 and RANKL in bone tissues were decreased (P<0.05) , and the expressions of LC3-II, LC3-II/LC3-I, ALP, Osterix and Runx2 were increased (P<0.05) . Conclusion: RAPA may activate autophagy by inhibiting mTOR phosphorylation, and inhibit bone resorption while promoting bone formation, thus alleviating early osteoporosis in skeletal fluorosis rats.

Effects of Different Hemodialysis Treatments on Abnormal Mineral and Bone Metabolism in Patients with Chronic Renal Failure

Objective: To investigate the effects of different hemodialysis treatments on abnormal mineral and bone metabolism in patients with chronic renal failure. Methods: A random number table was used to divide 80 patients with chronic renal failure admitted to our hospital from January 2018 to January 2019 into 2 groups, with 40 cases in each group. Group A was treated with low-flux hemodialysis, and group B was treated with high-flux hemodialysis. The related indicators of mineral and bone metabolism of the two groups were compared. Results: Before treatment, the blood calcium, blood phosphorus, intact parathyroid hormone (iPTH), type I procollagen amino terminal peptide (PINP), fibroblast growth factor 23 (FGF23), serum creatinine (Scr) indicators of the two groups were compared. The difference was not statistically significant(P&gt;0.05); After treatment, the blood calcium levels of the two groups were higher than before treatment, the blood phosphorus, iPTH, PINP, FGF23, and Scr levels were lower than before treatment, and the blood calcium level of group B was higher than that of group A, while blood phosphorus, iPTH, PINP, FGF23, and Scr levels were lower than group A, the difference was statistically significant (P&lt;0.05). Conclusion: Compared with low-flux hemodialysis, patients with chronic renal failure treated with high-flux hemodialysis have better results, which can correct abnormal bone metabolism and improve Scr levels.

FibroBox: a novel noninvasive tool for predicting significant liver fibrosis and cirrhosis in HBV infected patients

BackgroundChina is a highly endemic area of chronic hepatitis B (CHB). The accuracy of existed noninvasive biomarkers including TE, APRI and FIB-4 for staging fibrosis is not high enough in Chinese cohort.MethodsUsing liver biopsy as a gold standard, a novel noninvasive indicator was developed using laboratory tests, ultrasound measurements and liver stiffness measurements with machine learning techniques to predict significant fibrosis and cirrhosis in CHB patients in north and east part of China. We retrospectively evaluated the diagnostic performance of the novel indicator named FibroBox, Fibroscan, aspartate transaminase-to-platelet ratio index (APRI), and fibrosis-4 index (FIB-4) in CHB patients from Jilin and Huai’an (training sets) and also in Anhui and Beijing cohorts (validation sets).ResultsOf 1289 eligible HBV patients who had liver histological data, 63.2% had significant fibrosis and 22.5% had cirrhosis. In LASSO logistic regression and filter methods, fibroscan results, platelet count, alanine transaminase (ALT), prothrombin time (PT), type III procollagen aminoterminal peptide (PIIINP), type IV collagen, laminin, hyaluronic acid (HA) and diameter of spleen vein were finally selected as input variables in FibroBox. Consequently, FibroBox was developed of which the area under the receiver operating characteristic curve (AUROC) was significantly higher than that of TE, APRI and FIB-4 to predicting significant fibrosis and cirrhosis. In the Anhui and Beijing cohort, the AUROC of FibroBox was 0.88 (95% CI, 0.72–0.82) and 0.87 (95% CI, 0.83–0.91) for significant fibrosis and 0.87 (95% CI, 0.82–0.92) and 0.90 (95% CI, 0.85–0.94) for cirrhosis. In the validation cohorts, FibroBox accurately diagnosed 81% of significant fibrosis and 84% of cirrhosis.ConclusionsFibroBox has a better performance in predicting liver fibrosis in Chinese cohorts with CHB, which may serve as a feasible alternative to liver biopsy.

Short-Term Versus 6-Week Prednisone In The Treatment Of Subacute Thyroiditis: A Randomized Controlled Trial

Moderate-to-severe subacute thyroiditis is clinically managed with 6 to 8 weeks of glucocorticoid therapy. However, no studies have evaluated short-term prednisone treatment for subacute thyroiditis. This 24-week, prospective, single-blind, randomized controlled study enrolled patients (aged 18 to 70 years) with subacute thyroiditis who were hospitalized between August, 2013, and December, 2014. Patients with moderate-to-severe symptoms were randomly assigned to receive either 30 mg/day prednisone for 1 week, followed by 1 week of nonsteroidal anti-inflammatory drugs, or the conventional 6-week prednisone therapy. The primary endpoint was intergroup differences in treatment efficacy at the end of the treatment course. Secondary endpoints included between-group differences in post-withdrawal adverse effect parameters and thyroid function at weeks 6, 12, and 24. We screened 96 patients, randomized 52 participants, and 50 participants completed the study. Efficacy and recurrence rates were not significantly different at withdrawal in both groups (P = .65). At treatment discontinuation, parathyroid hormone (28.8 versus 38.9 pg/mL; P = .011) and systolic blood pressure (113.9 versus 122.4mm Hg; P = .023) were significantly lower in the experimental group than in the control group. There were no significant intergroup differences in other secondary endpoints at withdrawal and in thyroid function at weeks 6, 12, and 24. Fewer side effects of glucocorticoids and similar efficacy and recurrence rates were observed with short-term prednisone compared with the 6-week treatment for subacute thyroiditis. Short-term prednisone, with a better safety profile, may be an alternative strategy for ameliorating moderate-to-severe symptoms of subacute thyroiditis. BPPG = breakfast postprandial plasma glucose; CRP = C-reactive protein; ESR = erythrocyte sedimentation rate; FPG = fasting plasma glucose; FT3 = free triiodothyronine; FT4 = free thyroxine; GA = glycated albumin; NSAIDs = nonsteroidal anti-inflammatory drugs; OC = osteocalcin; PINP = type I procollagen amino-terminal peptide; PTH = parathyroid hormone; RCT = randomized controlled trial; SAT = subacute thyroiditis; SBP = systolic blood pressure; TC = total cholesterol; TSH = thyroid-stimulating hormone; TBG = thyroid-binding globulin; TG = triglyceride; TGAb = antithyroglobulin antibody; TPOAb = antithyroid peroxidase antibody; TRAb = antithyroid-stimulating hormone receptor antibody.

The influence and clinical significance of proteasome inhibitor on serum bone metabolite markers in patients with myeloma bone disease

Objective: To investigate the influence and clinical significance of proteasome inhibitor on serum bone metabolite markers including tartrate-resistant acid phosphatase 5b isoenzyme (TRACP-5b), type I collagen carboxy terminal peptide β(β-CTX), type I procollagen amino terminal prolongation peptide (PINP) and vitamin D3 in patients with myeloma bone disease (MBD). Methods: From April 2015 to June 2018, 68 patients with newly diagnosed MBD who admitted to our hospital were treated with proteasome inhibitor-based regimen. Serum concentration of TRACP-5b、β-CTX、PINP and vitamin D3 were measured before treatment and after 4 and 8 cycles of chemotherapy, and imaging changes were observed. Results: After 4 and 8 cycles of chemotherapy, serum levels of TRACP-5b, β-CTX and vitamin D3 were decreased significantly (P<0.05). The serum concentration of PINP was (78.1±44.9) ng/L before chemotherapy, while after 4 cycles, it turned to (94.5±56.1) ng/L without significant difference (t=-1.871, P=0.063). Moreover, it increased to (173.3±80.5) ng/L after 8 cycles of chemotherapy with significant difference (t=-8.272, P<0.001). The proportion of imaging classification ≥3 among all patients was 66.2%, and it decreased to 60.3% after 4 cycles of chemotherapy without significant difference (χ(2)=0.569, P=0.477). The proportion of imaging classification ≥3 after 8 cycles of chemotherapy decreased to 44.5%, which was significantly lower than that before treatment (χ(2)=6.260, P=0.012). After 8 cycles of chemotherapy, 63 patients were evaluable, of which 50 were effective and 13 were ineffective. Serum concentration of PINP in the effective group was higher than that in the ineffective group ((190.7±78.5) ng/L vs (106.5±47.3) ng/L,t=5.762, P<0.001), and the serum concentration of vitamin D3 in the effective group was lower than that in the ineffective group ((11.7±4.8) μg/L vs (15.6±5.5) μg/L, t=-2.478, P=0.016). The proportion of patients with more than grade 3 bone disease of the effective group was also significantly lower than that of the ineffective group (38.0% vs 69.2%, χ(2)=4.076, P=0.044). There was no significant difference in the serum concentration of TRACP-5b and β-CTX between two groups. Conclusion: After treatment with the proteasome inhibitor -based regimen, the serum concentrations of TRACP-5b, β-CTX and vitamin D3, which reflect osteoclast activity in MBD patients were decreased, the serum concentration of PINP indicating osteoblast activity was increased, and the grade of imaging of bone disease was decreased.

Relationship between changes of electrocardiogram indexes in chronic heart failure with arrhythmia and serum PIIINP and BNP.

Relationship between changes of electrocardiogram (ECG) indexes in chronic heart failure (CHF) with arrhythmia and serum type III procollagen amino-terminal peptide (PIIINP) and brain natriuretic peptide (BNP) were evaluated. From December 2017 to December 2018, 101 patients with heart failure (HF) were collected. Among them, 48 patients with HF and slow arrhythmia were in group A, and 53 cases of HF with non-slow arrhythmia were sin group B, including 33 males and 20 females. BNP was detected by chemiluminescence and PIIINP was detected by immunoassay. The changes of ECG indexes in the two groups, the correlation between serum PIIINP and BNP and NYHA classification of cardiac function, and the correlation between ECG indexes and PIIINP and BNP were detected. ROC curve analysis of BNP and PIIINP in the diagnosis of slow HF was carried out. Serum PIIINP and BNP in group A were significantly higher than those in group B (P<0.05). The levels of PIIINP and BNP in serum of NYHA patients with different cardiac functions, and those in serum of patients with class III were significantly higher than those of group II (P<0.05), while significantly lower than those of group IV (P<0.05). The heart rate and Q-T interval in group A were significantly higher than those in group B (P<0.05). The P-R interval and QES wave group in group A were significantly lower than those in group B (P<0.05). BNP had a positive correlation with Hr and G-T, and was negatively correlated with P-R and QRS; PIIINP was positively correlated with Hr and G-T, and had a negative correlation with P-R, QRS and BNP; PIIINP had positive correlation with NYHA; ECG indexes were correlated with BNP and PIIINP, and had diagnostic value for CHF. Using ECG indexes to predict BNP and PIIINP levels was conducive to the diagnosis of CHF.

Pulsed electromagnetic fields improve bone mineral density and bone metabolism after stroke

Objective To investigate the effect of a pulsed electromagnetic field (PEMFS) on bone mineral density and bone metabolism in males with osteoporosis after a stroke. Methods Fifty male stroke survivors with osteoporosis were randomly divided into a control group and a treatment group, both of 25. Both groups were treated with routine rehabilitation, oral calcium carbonate and vitamin D3 tablets, while the treatment group was additionally provided with PEMFS treatment. The subjects′ bone mineral density (BMD) and their blood levels of bone-specific alkaline phosphatase (B-ALP), type I procollagen amino-terminal peptide (PINP) and type β-I collagen cross-linked carboxy-terminal peptide (β-CTx) were measured before and after the 12 weeks of treatment. Results After the treatment the BMD values of the lumbar spine, femoral neck, trochanter and Ward′s triangle had increased significantly in both groups, but the average BMD values of the lumbar spine and femoral neck in the treatment group were significantly higher than those of the control group. After the treatment, the average B-ALP, PINP and β-CTx levels of both groups had also improved significantly compared with before the treatment, but the average improvement in all three among the treatment group was significantly greater than among the controls. Conclusion PEMFS treatment supplementing routine rehabilitation, oral calcium carbonate and vitamin D3 tablets can improve bone formation, reduce bone resorption and increase bone mineral density in men after a stroke. Key words: Electromagnetic fields; Pulsed electromagnetic fields; Bone metabolism; Bone mineral density

Association of bone metabolic markers with coronary artery disease and coronary arthrosclerosis in postmenopausal women

Objective The aim of this study was to examine the relationship between bone metabolic markers and coronary artery disease(CAD)and coronary atherosclerosis in postmenopausal women. Methods Subjects were the postmenopausal women who were admitted to the Department of Cardiology of Zhongshan Hospital for suspected CAD and underwent coronary angiography. 60 angiography confirmed CAD subjects and 60 angiography confirmed non-CAD subjects were recruited in the current study. A standard questionnaire was completed for each participant. Biochemical parameters and bone metabolic markers including parathyroid hormone(PTH), 25-hydroxyvitamin D3[25(OH)D3], type Ⅰ collagen cross-linked C-telopeptide(CTX), type Ⅰ procollagen amino-terminal peptide(PINP), and osteocalcin were determined. Results Serum CTX levels were significantly decreased in the CAD group compared with those of non-CAD group(P<0.05). The proportion of CAD decreased across the CTX tertiles(70%, 50%, and 30%, respectively, P=0.04). After adjustment by age, body mass index, smoking, systolic blood pressure, diastolic blood pressure, diabetes, hypertension, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and estimated glomerular filtration rate, the risk of CAD significantly decreased in the third CTX tertile compared to the first CTX tertile(OR=0.05, 95%CI 0.01-0.43, P=0.01). Multivariate linear regression analysis showed that serum CTX was independently associated with the Gensini score(β=-55.19, 95%CI -106.47--3.90, P=0.04). However, PTH, 25(OH)D3, PINP, and osteocalcin were not associated with CAD or the Gensini score. Conclusion Serum CTX was independently associated with CAD as well as the severity of coronary arthrosclerosis in postmenopausal women. (Chin J Endocrinol Metab, 2016, 32: 928-933) Key words: Bone metabolic marker; Coronary artery disease; Gensini score

Reverse effect of Yinchenhao decoction in dimethyl nitrosamine-induced hepatic fibrosis in rats

To discuss the reverse effect of Yinchenhao decoction(YCHD) in dimethyl nitrosamine (DMN)-induced hepatic fibrosis in rats. The rat hepatic fibrosis model was established through the intraperitoneal injection with 1% dimethyl nitrosamine (DMN) with a dose of 1.0 mL x kg(-1) x d(-1) for consecutively three weeks, once for the first three days of each. The rats were randomly divided into six groups: the silymarin positive control group (50.0 mg x kg(-1) x d(-1), YCHD high (20.0 g x kg(-1) d(-1)), middle (8.0 g x kg(-1) x d(-1)) and low (3.2 g x kg(-1) x d(-1)) dose groups, the model group and the normal control group. The model group and the normal control group were orally administered with normal saline for consecutively five weeks. The pathologic changes in liver tissues were observed by HE staining. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), g-glutamyltransferase (g-GGT), hyaluronic acid (HA), laminin (LN), collagen type IV (CIV) and type III procollagen amino terminal peptide (PIIINP) in serum were determined. The metabolite profiling of amino acid and the content of hydroxyproline in liver tissues were also measured. Compared with the model group, YCHD high and middle dose groups could significantly reverse the pathologic changes in liver tissues of rats. YCHD could reduce the levels of ALT, AST, gamma-GGT, HA, LN, CIV, PIIINP in serum and the content of hydroxyproline in liver tissues in a dose-dependent manner, and altered the metabolite profiling of amino acid in rat liver tissues. YCHD has the effect in reversing dimethyl nitrosamine induced hepatic fibrosis in rats.

Serum markers detect the presence of liver fibrosis: A cohort study

Histologic examination of a liver biopsy specimen is regarded as the reference standard for detecting liver fibrosis. Biopsy can be painful and hazardous, and assessment is subjective and prone to sampling error. We developed a panel of sensitive automated immunoassays to detect matrix constituents and mediators of matrix remodeling in serum to evaluate their performance in the detection of liver fibrosis. In an international multicenter cohort study, serum levels of 9 surrogate markers of liver fibrosis were compared with fibrosis stage in liver biopsy specimens obtained from 1021 subjects with chronic liver disease. Discriminant analysis of a test set of samples was used to identify an algorithm combining age, hyaluronic acid, amino-terminal propeptide of type III collagen, and tissue inhibitor of matrix metalloproteinase 1 that was subsequently evaluated using a validation set of biopsy specimens and serum samples. The algorithm detected fibrosis (sensitivity, 90%) and accurately detected the absence of fibrosis (negative predictive value for significant fibrosis, 92%; area under the curve of a receiver operating characteristic plot, .804; standard error, .02; P < .0001; 95% confidence interval, .758-.851). Performance was excellent for alcoholic liver disease and nonalcoholic fatty liver disease. The algorithm performed equally well in comparison with each of the pathologists. In contrast, pathologists' agreement over histologic scores ranged from very good to moderate (kappa = .97-.46). Assessment of liver fibrosis with multiple serum markers used in combination is sensitive, specific, and reproducible, suggesting they may be used in conjunction with liver biopsy to assess a range of chronic liver diseases.

Diagnostic accuracy of hyaluronan and type III procollagen amino-terminal peptide serum assays as markers of liver fibrosis in chronic viral hepatitis C evaluated by ROC curve analysis

Diagnostic accuracy of two serum markers of liver fibrosis, hyaluronan (HA) and amino-terminal peptide of type III procollagen (P-III-P), was studied in a cohort of 326 untreated patients with chronic viral hepatitis C. Both P-III-P (RIA-gnost P-III-P, Behring Diagnostic) and HA (HA-test, Pharmacia) serum concentrations correlated with the histological grades of liver fibrosis (P < 0.001). Receiver-operating characteristic (ROC) curves showed that serum HA had greater diagnostic performance than P-III-P, both for discriminating patients with extensive liver fibrosis from those with no or mild fibrosis (area under the ROC curves: 0.864 vs 0.691, P <0.001) or for discriminating patients with cirrhosis from those without cirrhosis (area under the ROC curves: 0.924 vs 0.734, P <0.001). At cutoff values of 0.8 kU/L for serum P-III-P and 85 micrograms/L for serum HA, sensitivities were 70.0% and 64.5%, and specificities were 63.4% and 91.2%, respectively, for discriminating patients with extensive liver fibrosis from those with no or mild fibrosis. At the cutoff values of 1.0 kU/L for serum P-III-P and 110 micrograms/L for serum HA, sensitivities were 60.0% and 79.2%, and specificities were 74.0% and 89.4%, respectively, for discriminating patients with liver cirrhosis from those without cirrhosis. We conclude that, because the diagnostic accuracy of serum HA is greater than that of serum P-III-P as a marker of liver fibrosis, serum HA should be preferred when monitoring liver fibrosis in patients with chronic viral hepatitis C.

Abnormalities of serum type III procollagen aminoterminal peptide in methotrexate-treated psoriatic patients with normal liver histology do not correlate with hepatic ultrastructural changes.

In a previous study, it was shown that the serum levels of type III procollagen aminoterminal peptide (P3NP) were significantly greater in patients receiving methotrexate (MTX) treatment for psoriasis than in untreated control patients with psoriasis. Although levels were highest in patients with hepatic fibrosis and cirrhosis, serum P3NP concentrations in those patients with normal liver histology on light microscopy were also shown to be significantly higher than in controls. In the present study, liver biopsies from 22 such 'normal' patients were examined by electron microscopy, in order to determine whether P3NP levels correlated with ultrastructurally demonstrable fibrosis. Fibrosis in the perisinusoidal space of Disse was present in as many as 82% of biopsies. Although the prevalence of such fibrosis in psoriasis patients who have not received MTX is unknown, the high prevalence of Disse space fibrosis and of raised P3NP in MTX-treated patients suggests that MTX causes subtle liver damage in a majority of treated patients. However, we were unable to show a statistical correlation between P3NP and the degree of Disse space fibrosis.