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Background. The association between free triiodothyronine (FT3) and long-term prognosis in dilated cardiomyopathy (DCM) patients has not been evaluated. The purpose of this study was to determine whether the level of FT3 could provide prognostic value in patients with DCM. Methods. Data of consecutive patients diagnosed with DCM were collected from October 2009 to December 2014. FT3 was measured by fluoroimmunoassay. Other biochemical markers, such as free thyroxin (FT4), thyroid-stimulating hormone, red blood cell, hemoglobin, blood urea nitrogen, and serum creatinine, were tested at the same time. Follow-up was performed every 3 months. The primary endpoint was all-cause mortality. Pearson analysis was used to evaluate the correlation of FT3 and other lab metrics with DCM patients’ prognosis. The association of long-term mortality in DCM and FT3 was compared using Cox hazards model. Results. Data of 176 patients diagnosed with DCM were collected. Of them, 24 patients missed FT3 values and six patients were lost to follow-up. Altogether, data of 146 patients were analyzed. During the median follow-up time of 79.9 (53.5–159.6) months, nine patients lost, 61 patients died (non-survival group), and 85 patients survived (survival group). FT3 was significantly lower in non-survival group than that in survival group (3.65 ± 0.83 pmol/L vs. 4.36 ± 1.91 pmol/L; P = 0.003). FT3 also showed a significantly positive correlation with red blood cell and hemoglobin, negatively correlated with age, blood urea nitrogen and serum creatinine (P

Young donors are associated with a lower cumulative incidence of acute graft‐vs‐host disease (aGVHD) after allogenic haematopoietic stem cell transplantation (allo‐HSCT) than old donors. Although grafts are harvested from healthy donors, it is unclear whether donor age is associated with aGVHD occurrence owing to its effect on cell compositions in grafts. Moreover, the differences in monocyte subsets in grafts between young and old donors and the association between monocyte subsets in bone marrow (BM) grafts and aGVHD remain to be elucidated. In the current study, non‐classical monocytes and the CD4+/CD8+ T cell ratio were remarkably decreased in BM grafts in donors

BACKGROUND Type 2 diabetes mellitus (T2DM) is associated with a higher fracture risk. Sex hormones are important for maintaining skeletal health. It is not clear which sex hormone(s) contribute(s) to bone mineral density (BMD) and fracture risk in males with T2DM. This study investigated the relationships of these parameters in males with T2DM. METHODS This study involved 482 men with T2DM. BMDs at the lumbar spine (L2-4), femoral neck (FN), and total hip (TH) were measured by dual-energy X-ray absorptiometry (DXA). The 10-year probability of fractures was assessed using the modified Fracture Risk Algorithm (FRAX) tool. Serum levels of sex hormones were measured. RESULTS Follicle-stimulating hormone (FSH) and estradiol (E2) were associated with BMDs at L2-4 (FSH, β = -.162, P < .05; E2, β = .176, P < .001), and E2 was associated with BMD at FN (β = .137, P < .05) and TH (β = .140, P < .05). FSH was associated with major osteoporotic fractures (β = .288, P < .001) and hip fractures (β = .235, P < .001). Higher FSH was a risk factor for osteoporosis/osteopenia (odds ratios [OR] = 2.92, 95% CI = 1.66-5.14, P

Objective: To summarize the characteristics of patients with pituitary stalk thickening, analyze the association between pituitary stalk width and hypopituitarism, and develop a diagnostic model to differentiate neoplastic and inflammatory origins. Methods: A total of 325 patients with pituitary stalk thickening in a tertiary teaching hospital between January 2012 and February 2018 were enrolled. Basic characteristics and hormonal status were evaluated. Indicators to predict etiology in patients with histologic diagnoses were analyzed. Results: Of the 325 patients, 62.5% were female. Deficiency in gonadotropin was most common, followed by corticotropin, growth hormone, and thyrotropin. The increase in pituitary stalk width was associated with a risk of central diabetes insipidus (odds ratio lOR], 3.57; P Conclusion: Pituitary stalk width could indicate the presence of anterior pituitary dysfunction, especially in central diabetes insipidus patients. With the use of a diagnostic model, the neoplastic and inflammatory causes of pituitary stalk thickening could be preliminarily differentiated. Abbreviations: APD = anterior pituitary dysfunction; AUC = area under the curve; CDI = central diabetes insipidus; GH = growth hormone; MRI = magnetic resonance imaging; OR = odd ratio; PHBS = posterior hypophyseal bright spots; PST = pituitary stalk thickening; PSW = pituitary stalk width

Background Parathyroid hormone related protein (PTHrP) triggers white adipose tissue (WAT) browning and cachexia in lung cancer mouse models. It remains unknown whether excessive PTH secretion affects WAT browning and to what extent it contributes to body weight change in primary hyperparathyroidism (PHPT). Methods Using the adeno-associated virus injection, Pth gene over-expressed mice mimicking PHPT were firstly established to observe their WAT browning and body weight alteration. The association between PTH and body weight was investigated in 496 PHPT patients. The adipose browning activities of 20 PHPT and 60 control subjects were measured with PET/CT scanning. Findings Elevated plasma PTH triggered adipose tissue browning, leading to increased energy expenditure, reduced fat content, and finally decreased body weight in PHPT mice. Higher circulating PTH levels were associated with lower body weight (β = −0.048, P = .0003) independent of renal function, serum calcium, phosphorus,and albumin levels in PHPT patients. PHPT patients exhibited both higher prevalence of detectable brown/beige adipose tissue (20% vs 3.3%, P = .03) and increased browning activities (SUV in cervical adipose was 0.77 vs 0.49,P = .02) compared with control subjects. Interpretation Elevated serum PTH drove WAT browning program, which contributed in part to body weight loss in both PHPT mice and patients. These results give insights into the novel pathological effect of PTH and are of importance in understanding the metabolic changes of PHPT. Fund This research is supported by the National Key Research and Development Program of China and National Natural Science Foundation of China.

Objective Up to 40% of multiple endocrine neoplasia type 1 (MEN1) patients may have adrenal cortical tumors. However, adrenocortical carcinoma (ACC) is rare. The clinical manifestations, prevalence, inheritance and prognosis of ACC associated with MEN1 remain unclear. Here we report the clinical manifestations and prevalence of ACC in patients with MEN1. Design and methods A retrospective analysis of ACC associated with MEN1 patients at a single tertiary care center from December 2001 to June 2017. Genetic analysis of MEN1 and other ACC associated genes, loss of heterozygosity (LOH) of MEN1 locus, immunohistochemistry staining of menin, P53 and β-catenin in ACC tissue were performed. Results Two related patients had ACC associated with MEN1. The father had ENSAT stage IV tumor with excessive production of cortisol; the daughter had nonfunctional ENSAT stage I tumor. Both patients carried novel germline heterozygous mutation (c.400_401insC) of MEN1. The wild-type MEN1 allele was lost in the resected ACC tissue from the daughter with no menin staining. The ACC tissue had nuclear β-catenin staining, with heterozygous CTNNB1 mutation of 357del24 and P53 staining in only 20% cells. Conclusions ACC associated with MEN1 is rare and may occur in familial aggregates.

ObjectivesThe aim of this study was to investigate factors responsible for the psychological performance in primary hyperparathyroidism (PHPT) patients.MethodsA group of 38 PHPT patients receiving questionnaires, including Beck Depression Inventory (BDI), State–Trait Anxiety Inventory (STAI), and 36-Item Short Form Survey (SF-36), was evaluated. The relationships between scores of questionnaires and clinical biomarkers were examined. Collinearity and linear regression model were applied to examine variables determining the scores of the questionnaire. In 192 PHPT patients, bivariate and partial correlation were used to analyze the relationships between serum concentrations of parathyroid hormone (PTH), calcium, osteocalcin (OCN), and cortisol.ResultsAmong 38 patients receiving questionnaire tests, 50% (19/38) of the patients developed state anxiety, 60.5% (23/38) of the patients had the trait of developing anxiety. In addition, 18.4% (7/38) of the patients developed mild to severe depression. Serum cortisol at 8:00 was negatively and significantly correlated with social function (r = -0.389, p = 0.041) after controlling for age, sex, disease duration, serum PTH, calcium, phosphorus, and 25-hydroxyvitamin D [25(OH)D] concentration. OCN was significantly and negatively correlated with score of STAI-S (r = -0.426, p = 0.027). In the linear regression model for BDI score, variables with statistical significance were serum OCN (β = -0.422, p = 0.019) and cortisol at 0:00 (β = 0.371, p = 0.037). In 192 PHPT patients, the serum concentration of OCN (r = 0.373, p = 0.000) was positively correlated with PTH level. After controlling for age, sex, disease duration, serum 25(OH)D, phosphorus, and calcium concentration, the positive correlation between OCN and PTH was still statistically significant (r = 0.323, p = 0.000). The serum concentration of cortisol at 0:00 was significantly and positively correlated with serum calcium (r = 0.246, p = 0.001) in bivariate correlation analysis. After controlling for age, sex, disease duration, serum PTH, 25(OH)D, and phosphorus concentration, serum cortisol at 0:00 was still positively and significantly correlated with serum calcium (r = 0.245, p = 0.001).ConclusionSerum levels of OCN and cortisol, rather than PTH and calcium, are associated with the development of anxiety and depression symptoms in PHPT patients.

Background. Cervical ultrasound, 99mTc-sestamibi single-photon emission computed tomography/computed tomography (99mTc-MIBI SPECT/CT), and cervical CT are routinely used in preoperative localization of primary hyperparathyroidism (PHPT). However, false-negative imaging results are also frequently encountered in clinical practice. Exploring the factors that affect the sensitivity of these imaging modalities is important for the surgical management of PHPT patients. Methods. Clinical data of 352 PHPT patients hospitalized in our center from January 2011 to December 2015 were retrospectively collected to evaluate the sensitivity of 3 imaging modalities in the preoperative localization of parathyroid lesions. The ROC curve analysis was used to explore the clinical factors affecting the sensitivity of localization, and the cut-point(s) of related factors were determined. Results. 99mTc-MIBI SPECT/CT has the highest sensitivity among the localization modalities commonly used, reaching 91.1% (86.0%–94.8%). When the lengths of parathyroid lesions were ≤1.3 cm, the sensitivity of neck ultrasonography significantly decreased, while the sensitivity of 99mTc-MIBI SPECT/CT decreased with parathyroid lesions ≤1.3 cm or serum PTH≤252 pg/ml. 99mTc-MIBI SPECT/CT was less effective in localizing the hyperplasia lesions. Neck ultrasonography combined with 99mTc-MIBI SPECT/CT can effectively improve the accuracy of preoperative localization of parathyroid lesions to 96.2% (92.7%–98.1%). Conclusions. Small parathyroid lesion and mild elevation of serum PTH would reduce the accuracy of parathyroid localization in PHPT patients.

To investigate the relationship between parathyroid hormone (PTH) levels and body weight, body mass index (BMI), lipid profiles, and fat distribution in subjects with primary hyperparathyroidism (PHPT) and controls. This was a cross-sectional study in 192 patients with PHPT and 202 controls. Serum concentrations of calcium, 25-hydroxyvitamin D (25(OH)D), PTH, lipids profiles, and other hormones were quantified. Bone mineral density was assessed by dual-energy X-ray absorptiometry. Fat distribution evaluation utilizing quantitative computed tomography was conducted in another 66 patients with PHPT and 155 controls. PHPT patients were older (P

This paper aims to describe the development of research on corporate social responsibility in international business (IB) journals and to suggest future research directions. We conducted a bibliometric study of articles published in twelve leading international business journals over three decades in a longer time frame (1996–2015). Five research trends were found in IB journals: business ethics, integration of stakeholder management, the evolution of the CSR concept, the political and social demands of CSR, and the financial implications of CSR. Our results thus have several implications and suggest numerous opportunities for future research.

In the current study, we investigated the vitamin D status, and its relationships with parathyroid hormone (PTH) levels, bone mineral density (BMD), and the 10-year probability of fractures in Chinese patients with type 2 diabetes mellitus (T2DM).This was a cross-sectional study of 785 patients. BMDs at the lumbar spine (L2-4), femoral neck (FN), and total hip (TH) were measured by dual-energy X-ray absorptiometry (DXA). Serum levels of 25-hydroxyvitamin D (25(OH)D) and intact PTH were also quantified. The 10-year probability of fracture risk (major osteoporotic fracture [MOF] and hip fracture [HF]) was assessed using the fracture risk assessment tool (FRAX).The prevalence of vitamin D deficiency was 82.3%, and the mean 25(OH)D level was 36.9 ± 15.2 nmol/L. The adequate group had higher BMDs at the FN and TH and lower MOF risk than the inadequate groups. Lower 25(OH)D was associated with higher PTH ( r = -0.126, P.001). PTH was negatively correlated with BMDs at 3 sites and positively correlated with MOF and HF, but this relationship disappeared in the adequate subgroup. Multivariate stepwise regression analysis revealed that PTH was the determinant of MOF (standard β = 0.073, P = .010) and HF (standard β = 0.094, P = .004).Our results identified a significantly high rate of vitamin D deficiency among Chinese patients with T2DM. PTH is an important risk factor responsible for the higher 10-year probability of osteoporotic fractures in diabetic patients, especially in those with lower vitamin D levels.AKP = alkaline phosphatase; ALB = serum albumin; BMD = bone mineral density; BMI = body mass index; Ca = calcium; CKD = chronic kidney disease; Cr = creatinine; FN = femoral neck; FRAX = fracture risk assessment tool; HbA1c = glycated hemoglobin A1c; HF = hip fracture; L2-4 = lumbar spine; MOF = major osteoporotic fracture; 25(OH)D = 25-hydroxyvitamin D; P = phosphorus; PTH = parathyroid hormone; T2DM = type 2 diabetes mellitus; TH = total hip; UA = uric acid.

We aimed to investigate associations among serum levels of LCN2, bone resorption marker carboxy-terminal cross-linking telopeptide of type-1 collagen (CTx), bone formation marker osteocalcin (OCN), and bone mineral densities (BMDs) in ambulatory healthy women. This cross-sectional study analyzed 1012 previously enrolled outpatient Han Chinese women. BMDs of the lumbar spine and femoral neck were measured using dual energy X-ray absorptiometry. Serum levels of LCN2, CTx, OCN, and creatinine (Scr) were measured. Circulating LCN2 was inversely correlated with BMDs at the lumbar spine and femoral neck (Spearman’s r = −0.08, P = 0.010 and r = −0.14, P

We propose an optimal approach to solve the problem of multi-degree reduction of C-Bezier surfaces in the norm L2 with prescribed constraints. The control points of the degree-reduced C-Bezier surfaces can be explicitly obtained by using a matrix operation that is based on the transfer matrix of the C-Bezier basis. With prescribed boundary constraints, this method can be applied to piecewise continuous patches or to a single patch with the combination of surface subdivision. The resulting piecewise approximating patches are globally G1 continuous. Finally, numerical examples are presented to show the effectiveness of the method.

Background: Myelodysplastic syndromes (MDS) are a group of heterogeneous myeloid clonal disorders characterized by ineffective hematopoiesis, refractory anemia, and a tendency to transform to acute myeloid leukemia (AML). Ineffective hematopoiesis progression and immune deregulation are dominating pathophysiological process of MDS. Emerging evidences showed the role of bone marrow (BM) microenvironment in MDS. In MDS murine model, integral BM microenvironment contributes to inferior hematopoietic function and disease progression. As an important component of BM microenvironment, the relationship between endothelial cells (ECs) and MDS progression remains largely unknown. Although ECs from MDS patients have been identified to have decreased supporting ability to normal hematopoietic stem cells (HSCs), the supporting ability of ECs in different clinical stages of MDS remains to be elucidated. In addition, the role of BM ECs from MDS patients in supporting leukemia cells and their immunomodulatory ability remains unclear. Aims: To determine the number and functions of BM ECs in different subtypes of MDS patients. Moreover, to explore the correlation between BM ECs and MDS progression, which may represent a potential therapeutic target for MDS patients. Methods: In the prospective cohort study, patients with multilineage dysplasia (MDS-MLD, N=15), MDS with excess blasts (MDS-EB, N=15), or AML(N=15) and healthy donors (HD, N=15) were enrolled. BM ECs were analyzed in HD and patients by flow cytometry and in situ histological analyses. The functions of BM ECs were analyzed by migration, angiogenesis capacities, levels of apoptosis and reactive oxygen species (ROS). To evaluate the supporting abilities of BM ECs on HSCs, leukemia cells and T cells, in vitro co-culture strategies were used. The levels of apoptosis, ROS and colony-forming unit-plating (CFU) efficiency of CD34+ and HL-60 cells were investigated. T cell subsets were analyzed by flow cytometry as previously reported. To further investigate the underlying mechanism of dysfunctional ECs, RNA sequencing (RNA-Seq) analyses and real time-PCR (qRT-PCR) were performed in BM ECs from HD and MDS patients with different subtypes. Results: In the current study, gradually increased BM ECs were observed from MDS-MLD, MDS-EB to AML patients. Furthermore, dysfunctional BM ECs were found with MDS progression, characterized by increased levels of migration, angiogenesis capacities, apoptosis and ROS. More importantly, BM ECs from MDS patients exhibited decreased supporting ability of HSCs whereas increased supporting ability of leukemia cells in vitro with MDS progression. After coculture with ECs, levels of apoptosis and ROS in CD34+ cells were increased whereas their CFU efficiency reduced. On the other hand, levels of apoptosis and ROS of HL-60 cells were decreased. The proliferation capacity and leukemia CFU efficiency of HL-60 cells after co-cultured with ECs were enhanced with MDS progression. Furthermore, following coculture with BM ECs, deregulated differentiation was demonstrated in T cell subsets, characterized by elevating proportion of Th2 and Treg and decreasing proportion of Th1 and Th17 with MDS progression. RNA-Seq showed that the expression profile of BM ECs from MDS-EB was closer to MDS-MLD, whereas that of MDS-EB was closer to AML. Different gene expression profiles indicated the expression of hematopoiesis and immune related genes increased in BM ECs with MDS progression. Mechanistically, the mRNA levels of CX CL12, SCF and NFKB of ECs were increased with MDS progression. Summary/Conclusion: In summary, the number of BM ECs gradually increased, BM EC dysfunction more and more severe, and the supporting abilities of BM ECs on HSCs decreased, whereas on leukemia cells increased with MDS progression. Moreover, ECs regulated the differentiation of T cells into immune tolerant cells with MDS progression. Although further validation is required, these findings indicated that the improvement of BM ECs may represent a potential therapeutic approach for MDS patients. Keywords: Myelodysplastic syndromes, endothelial cells, disease progression, ineffective hematopoiesis, immune deregulation Disclosures No relevant conflicts of interest to declare.

Background Aplastic anemia (AA) is a life-threatening disease characterized by bone marrow (BM) failure and pancytopenia. Immunosuppressive therapy can rescue most patients with AA. However, the pathogenesis of AA is still not well elucidated and the new strategies need to be developed for AA patients. Increasing evidences suggested the dysfunctional BM microenvironment may be involved in the pathogenesis of AA. As important components of the BM microenvironment, endothelial cells (ECs) play a crucial role in supporting hematopoiesis and regulating immune. However, whether BM ECs are involved in the occurrence of AA and whether repairing BM ECs could improve the hematopoietic and immune status of AA patients remain to be elucidated. Aims To evaluate the quantity and function of BM ECs from AA patients. Moreover, to determine whether the dysfunctional BM ECs are involved in the occurrence of AA by affecting hematopoiesis and regulating immunity in vitro and in vivo. Finally, to uncover the therapeutic potential of repairing dysfunctional BM ECs to alter the hematopoietic and immunological status in AA patients. Methods This study enrolled 30 patients with AA and 30 healthy donors(HD). Flow cytometry and BM in situ immunofluorescence staining were used to analyze the proportion of ECs in BM of the two groups. The level of intracellular reactive oxygen species(ROS) and the proportion of apoptosis were detected by flow cytometry. The functions of BM ECs were evaluated by double-positive staining, migration and tube formation assays. To determine the effect of BM ECs on hematopoiesis and immunity, primary human BM ECs were separately cocultured with CD34 + and CD3 + cells. To further validate the role of BM ECs in the occurrence of AA, a classical AA mice model and VE-cadherin blocking antibody that could antagonize the function of BM ECs were used. Moreover, to explore potential approach of targeting the dysfunctional BM ECs, the exogenous EC infusion or N-acetyl-L-cysteine (NAC, a ROS scavenger) for repairing BM ECs were administrated to the AA mice. To further explore the repairing effect of NAC on BM ECs, the primary BM ECs from AA patients were treated by NAC in vitroand then the functions of BM ECs were evaluated. Results Compared with HD, BM ECs in AA patients were decreased and dysfunctional, which characterized by higher levels of ROS and apoptosis, impaired abilities of migration and angiogenesis. Furthermore, dysfunctional BM ECs from AA patients not only impaired their hematopoiesis-supporting ability but also promoted co-cultured T cells to polarize towards pro-inflammatory T cells in vitro, which resulted in an unbalanced T cell subsets. Consistently, AA mice demonstrated decreased BM ECs with increased level of intracellular ROS. Moreover, hematopoietic failure and immune imbalance in AA mice became more severe when the function of BM ECs was antagonized, whereas the administration of NAC or infusion of exogenous EC improved the hematopoietic and immunological status of AA mice via repairing BM ECs in vivo. In addition, we found the NAC treatment also restored the hematopoiesis-supporting ability and immunity-regulating ability of the primary ECs derived from AA patients in vitro. Summary/Conclusion Our study demonstrates for the first time that dysfunctional BM ECs with impaired hematopoiesis-supporting ability and abnormal immunomodulatory ability are involved in the pathogenesis of AA. Although further validation is required, restoring dysfunctional BM ECs via EC infusion or administration of ROS scavenger NAC might be a potential therapeutic approach for AA patients. Disclosures No relevant conflicts of interest to declare.

Passive multistatic radar is of great interest in both civilian and military applications due to its numerous advantages. A linear fusion framework for target detection in the passive multistatic radar is proposed here to improve the detection performance. In our framework, the global decision is the weighted combination of the local test statistics from spatially separated receivers, and the individual test statistics are computed through cross-correlation. A modified deflection coefficient is introduced as an optimization criterion for the selection of the weighting coefficients. Particularly, we give the weighting coefficient in closed form which is computationally efficient to calculate. In addition, we derive a closed-form expression for the probability of false alarm of this system, which is verified using Monte Carlo simulations. Numerical examples illustrate that our proposed approach outperforms its counterparts.

Background: Acute graft-versus-host disease(aGVHD) remains a major complication following allogeneic hematopoietic stem cell transplantation(allo-HSCT). The pathogenesis of aGVHD is commonly considered to be caused by exaggerated and undesirable immune responses. Macrophages (MΦs) are an important immune population that are essential for disease pathogenesis. MΦs are now commonly classified as either M1, which produce pro-inflammatory cytokines, or M2, which produce anti-inflammatory cytokines. Our recent study reported that patients who received an allograft with a higher M1/M2 ratio exhibited a higher incidence of grade 2-4 aGVHD(BMT, 2019). Moreover, an aberrant M1/M2 polarization was found in the colon of aGVHD mice, and regulating the polarization of MΦs cultured from aGVHD patients towards M2 phenotype modulated T cells favoring a type 2 response in vitro(Sci China Life Sci, 2020). However, the primary subsets and function of MΦs in aGVHD patients, and the precise roles of different MΦ subsets in the development of aGVHD remain to be elucidated. Aims: To determine the subsets and function of MΦs in primary peripheral blood(PB) of aGVHD patients. Moreover, to investigate whether M1 and M2 had different effects on the development of aGVHD, which may provide a potential therapeutic target for aGVHD patients after allo-HSCT. Methods: In this prospective case-control study, a total of 20 patients with aGVHD and 20 matched patients without aGVHD(non-aGVHD) after allo-HSCT were enrolled. MΦ subsets were analyzed in aGVHD and non-aGVHD patients by flow cytometry. M1 and M2 were identified as CD14+CCR2+CD68+ and CD14+CX3CR1+CD163+, respectively. In order to determine the function of MΦs in patients with aGVHD and non-aGVHD, the phagocytosis was analyzed using a DiI-AcLDL assay. The protein expressions for the costimulatory molecules and the cytokine production of MΦs were measured by flow cytometry. To further investigate its mechanism, RNA sequencing (RNA-Seq) was performed to analyze the gene expression profiles of MΦs. Subsequently, to explore the role of different subsets of MΦs in the development of aGVHD, M1 and M2 were infused into aGVHD mice, respectively. Mice were monitored for survival, weight, and aGVHD score. Histological scores of tissues from aGVHD target organs (liver, intestine, spleen and skin) were evaluated by HE staining. Results: When compared with non-aGVHD patients, MΦs in primary PB of aGVHD patients were polarized towards pro-inflammatory M1, characterized by an elevated proportion of M1 and a reduced proportion of M2. Furthermore, MΦs isolated from aGVHD patients exhibited lower phagocytic function, higher expression of TNF-α and IL-6 and higher expression of costimulatory molecules CD80 and CD86. Consistent with the increased activated MΦs from aGVHD patients, the mRNA levels of genes involved in the pro-inflammatory M1 polarization, antigen presenting and promoting the activation of T cells pathway were substantially elevated in MΦs of aGVHD patients compared to those in non-aGVHD patients. Importantly, in vivo infusion with pro-inflammatory M1 aggravated aGVHD response by modulating immune microenvironment of spleen and liver in mice, characterized by enhanced effector function of T cell, including elevated percentages of Tc1, Th1 and Th17 as well as increased proliferation of T cells from spleen and liver. By contrast, infusion with anti-inflammatory M2 alleviated aGVHD through down-regulating the activity of T cells derived from aGVHD mice, characterized by decreased proliferation and decreased percentages of Tc1, Th1 and Th17. Summary/Conclusion: The current study demonstrated that the primary MΦs in aGVHD patients preferentially polarize into pro-inflammatory M1. Moreover, M1 aggravate aGVHD whereas M2 ameliorate aGVHD by differently modulating immune microenvironment. Although further validation is required, modulating the polarization state of MΦs promises to be a novel therapeutic target for aGVHD patients after allo-HSCT. Disclosures No relevant conflicts of interest to declare.

BACKGROUND: Postmenopause and type 2 diabetes mellitus (T2DM) are associated with higher fracture risk. Sex hormones are important in maintaining woman skeleton health. The relationships of sex hormone(s) with bone mineral density (BMD) and fracture risk are still unclear in diabetic-postmenopausal women. This study aimed to investigate the relationships of sex hormones with BMDs and fracture risk in postmenopausal women with T2DM. METHODS: Two hundred and fourteen postmenopausal women with T2DM were included. BMDs at lumbar spine (L2-4), femoral neck (FN) and total hip (TH) were measured by dual-energy X-ray absorptiometry (DXA). The 10-year probability of fractures was accessed by modified fracture risk algorithm (FRAX) tool. Serum concentrations of sex hormones were measured. RESULTS: Sex hormone binding globulin (SHBG) was a determinant of BMDs at L2-4 (β=−0.199, P

Idiopathic hypogonadotropic hypogonadism (IHH) patients are characterized by the absence of puberty and varying degrees of deteriorated metabolic conditions. Osteocalcin (OC) could regulate testosterone secretion and energy metabolism, but it remains unknown whether such an effect exists in IHH patients. Our study is aimed to examine the relationship between serum OC levels with testosterone and its responsiveness to gonadotropin stimulation and metabolic profiles in male IHH patients. A total of 99 male patients aged 18–37 years and diagnosed with IHH were enrolled in the current study, and the relationships between OC and testicular volume, baseline total testosterone (TT), free testosterone (FT), and peak TT (Tmax) levels after human chorionic gonadotropin (hCG) stimulation, gonadotropin responsiveness index (GRI), which is calculated by dividing Tmax by testicular volume, as well as metabolic profiles, such as 2-h post-challenge glucose (2hPG) and fat percentage (fat%), were analyzed. The results showed that OC had an independent negative relationship with testicular volume (r = −0.253, P = 0.012) and a positive association with Tmax (r = 0.262, P = 0.014) after adjusting for confounders. In addition, OC was a major determinant of GRI (adjusted R2 for the model = 0.164, P = 0.012), fat% (adjusted R2 for the model = 0.100, P = 0.004), and 2hPG (adjusted R2 for the model = 0.054, P = 0.013) in IHH patients. In conclusion, OC is associated with testosterone secretion upon gonadotropin stimulation, glucose metabolism, and fat mass variations in IHH. This study was registered at clinicaltrials.gov ({"type":"clinical-trial","attrs":{"text":"NCT02310074","term_id":"NCT02310074"}}NCT02310074).

Exposure to chronic stress can produce maladaptive neurobiological changes in pathways associated with pain processing, which may cause stress–induced hyperalgesia (SIH). However, the underlying mechanisms still remain largely unknown. In previous studies, we have reported that the amygdala is involved in chronic forced swim (FS) stress–induced depressive-like behaviors and the exacerbation of neuropathic pain in rats, of which, the basolateral amygdala (BLA) and the central nucleus of the amygdala (CeA) are shown to play important roles in the integration of affective and sensory information including nociception. Here, using in vivo multichannel recording from rostal anterior cingulate cortex (rACC) and BLA, we found that chronic FS stress (CFSS) could increase the pain sensitivity of rats in response to low intensity innoxious stimuli (LIS) and high intensity noxious stimuli (HNS) imposed upon the hindpaw, validating the occurrence of SIH in stressed rats. Moreover, we discovered that CFSS not only induced an increased activity of rACC neuronal population but also produced an augmented field potential power (FPP) of rACC local field potential (LFP), especially in low frequency theta band as well as in high frequency low gamma band ranges, both at the baseline state and under LIS and HNS conditions. In addition, by using a cross-correlation method and a partial directed coherence (PDC) algorithm to analyze the LFP oscillating activity in rACC and BLA, we demonstrated that CFSS could substantially promote the synchronization between rACC and BLA regions, and also enhanced the neural information flow from rACC to BLA. We conclude that exposure of chronic FS stress to rats could result in an increased activity of rACC neuronal population and promote the functional connectivity and the synchronization between rACC and BLA regions, and also enhance the pain–related neural information flow from rACC to BLA, which likely underlie the pathogenesis of SIH.

Cancer-associated pain is debilitating. Understanding the mechanisms that cause it can inform drug development that may improve quality of life in patients. Here, we found that the reduced abundance of potassium channels called TRESK in dorsal root ganglion (DRG) neurons sensitized nociceptive sensory neurons and cancer-associated pain. Overexpressing TRESK in DRG neurons suppressed tumor-induced neuronal hyperexcitability and pain hypersensitivity in bone metastasis model rats, whereas knocking down TRESK increased neuronal hyperexcitability and pain hypersensitivity in normal rats. Mechanistically, tumor-associated production of vascular endothelial growth factor (VEGF) activated the receptor VEGFR2 on DRGs, which increased the abundance of the calcineurin inhibitor DSCR1, which, in turn, decreased calcineurin-mediated activation of the transcription factor NFAT, thereby reducing the transcription of the gene encoding TRESK. Intrathecal application of exogenous calcineurin to tumor-bearing rats rescued TRESK abundance and abrogated both DRG hyperexcitability and pain hypersensitivity, whereas either inhibition or knockdown of calcineurin in normal rats reduced TRESK abundance and increased DRG excitability and pain sensitivity. These findings identify a potentially targetable mechanism that may cause bone metastasis-associated pain in cancer patients.

Brucellosis is an endemic disease in China affecting both humans and livestock. The aim of the present study was to analyze two Brucella strains isolated from sheep spleens from Ulanqab in Inner Mongolia, China using classical and molecular typing techniques. The two strains were identified as Brucella suis biovar 3 and were closely related to isolates previously obtained from two different hosts (human and swine) in Guangxi Province. Our results suggest that B. suis can be directly or indirectly transferred from swine to sheep, which act as reservoirs for B. suis infection and later transmitted to humans. Multiple locus variable-number tandem repeat analysis (MLVA) is a useful tool for tracing the geographical origin of brucellosis infections and elucidating its transmission patterns.

In this paper, a new algorithm is proposed for computing the node-disjoint optimal transmission energy consumption route for coded cooperative mobile IoT networks. Inspired by the potential benefits user cooperation can provide, we incorporate user cooperation to the mobile ad-hoc multi-hop IoT networks. Our results include a novel ant colony system-based node-disjoint energy-efficient routing algorithm. Ant colony system can approximate the optimal route by local information and is thus very suitable for mobile IoT network environment. In particular, ant algorithm makes history-sensitive choice and thus can significantly outperform the greedy algorithm. In addition, it can efficiently handle the case of multiple sources and multiple destinations. For a large IoT network, we investigate the multi-scale ant colony system and when compared to Dijkstra algorithm, such an algorithm usually shortens the runtime by a factor of several hundred.

Poor graft function (PGF) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is characterized by defective hematopoiesis. Mesenchymal stem cells (MSCs) have been shown to support hematopoiesis, but little is known about the role of MSCs in the pathogenesis of PGF. In the current prospective case-control study, we evaluated whether the number and function of bone marrow (BM) MSCs in PGF patients differed from those in good graft function (GGF) patients. We found that BM MSCs from PGF patients expanded more slowly and appeared flattened and larger, exhibiting more apoptosis and senescence than MSCs from GGF patients. Furthermore, increased intracellular reactive oxygen species, p-p53, and p21 (but not p38) levels were detected in MSCs from PGF patients. Moreover, the ability of MSCs to sustain hematopoiesis was significantly reduced in PGF patients, as evaluated by cell number, apoptosis, and the colony-forming unit–plating efficiency of CD34+ cells. In summary, the biologic characteristics of PGF MSCs are different from those of GGF MSCs, and the in vitro hematopoiesis-supporting ability of PGF MSCs is significantly lower. Although requiring further validation, our study indicates that reduced and dysfunctional BM MSCs may contribute to deficient hematopoiesis in PGF patients. Therefore, improvement of BM MSCs may represent a promising therapeutic approach for PGF patients after allo-HSCT.

Poor graft function (PGF) is a severe complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT). Murine studies have demonstrated that effective haematopoiesis depends on the specific bone marrow (BM) microenvironment. Increasing evidence shows that BM macrophages (MФs), which constitute an important component of BM immune microenvironment, are indispensable for the regulation of haematopoietic stem cells (HSCs) in the BM. However, little is known about the number and function of BM MФs or whether they directly interact with HSCs in PGF patients. In the current prospective case-control study, PGF patients showed a significant increase in classically activated inflammatory MФs (M1; 2·18 ± 0·11% vs. 0·82 ± 0·06%, P < 0·0001), a striking reduction in alternatively activated anti-inflammatory MФs (M2; 3·02 ± 0·31% vs. 21·89 ± 0·90%, P < 0·0001), resulting in a markedly increased M1/M2 ratio (0·82 ± 0·06 vs. 0·06 ± 0·002; P < 0·0001) in the BM compared with good graft function patients. Meanwhile, standard monocyte subsets were altered in PGF patients. Dysfunctional BM MФs, which were characterized by reduced proliferation, migration and phagocytosis, were evident in PGF patients. Furthermore, BM MФs from PGF patients with high tumour necrosis factor-α and interleukin 12 levels and low transforming growth factor-β levels, led to impaired BM CD34+ cell function. In summary, our data indicate that an unbalanced BM M1/M2 ratio and dysfunctional MФs may contribute to the occurrence of PGF following allo-HSCT.

Graft-versus-host disease (GVHD) is a major complication after allogeneic haematopoietic stem cell transplantation (allo-HSCT) that is frequently associated with bone marrow (BM) suppression, and clinical management is challenging. BM endothelial progenitor cells (EPCs) play crucial roles in the regulation of haematopoiesis and thrombopoiesis. However, little is known regarding the functional roles of BM EPCs in acute GVHD (aGVHD) patients. In the current prospective case-control study, reduced and dysfunctional BM EPCs, characterized by decreased migration and angiogenesis capacities and increased levels of reactive oxygen species (ROS) and apoptosis, were found in aGVHD patients compared with those without aGVHD. Moreover, lower frequency and increased levels of ROS, apoptosis and DNA damage, but reduced colony-forming unit-plating efficiency were found in BM CD34+ cells of aGVHD patients compared with those without aGVHD. The severity of aGVHD and GVHD-mediated cytopenia was associated with BM EPC impairment in aGVHD patients. In addition, the EPC impairment positively correlated with ROS level. Taken together, our results suggest that reduced and dysfunctional BM EPCs may be involved in the pathogenesis of aGVHD. Although these findings require validation, our data indicate that improvement of BM EPCs may represent a promising therapeutic approach for aGVHD patients.

Background Accumulating evidences demonstrate that abnormalities in whole blood viscosity (WBV) have been implicated in insulin resistance which may lead to non-alcoholic fatty liver disease (NAFLD). However, epidemiological studies exploring the association between WBV and NAFLD were not available. Objective Our objective was to evaluate the association between WBV levels and risk of prevalent NAFLD. Design This was a cross-sectional population-based study performed in Shanghai, China. Patients A total of 8673 participants aged 40 years or older were included. Measurements WBV was calculated from haematocrit and plasma protein concentration, at a shear rate of 208(-1) s, by a validated equation. NAFLD was diagnosed by hepatic ultrasound after the exclusion of alcohol abuse and other liver diseases. Insulin resistance (IR) was assessed by homeostasis model assessment (HOMA-IR). Results The overall prevalence of NAFLD was 30·2% in this population. With the increase of WBV level, participants have larger waist circumference (WC), more severe insulin resistance and the prevalence of NAFLD increased significantly with elevated WBV quartiles. Compared with those in the lowest quartiles, adults in the highest quartile of WBV levels have higher prevalence of NAFLD (adjusted odds ratio 1·77, 95% confidence interval [CI] 1·48-2·13) and IR (2·72, 95% CI 2·26-3·27). Conclusions Elevated WBV is associated with prevalence of NAFLD and IR in middle-aged and elderly Chinese population.

Objective: We investigated whether disturbance of calcium and phosphate metabolism is associated with the presence and severity of calcific aortic valve disease (CAVD) in patients with normal or mildly impaired renal function. Methods: We measured serum levels of calcium, phosphate, alkaline phosphatase (AKP), intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25-OHD), and biomarkers of bone turnover in 260 consecutive patients with normal or mildly impaired renal function and aortic valve sclerosis (AVSc) (n=164) or stenosis (AVS) (n=96) and in 164 age- and gender-matched controls. Logistic regression models were used to determine the association of mineral metabolism parameters with the presence and severity of CAVD. Results: Stepwise increases were observed in serum levels of calcium, phosphate, AKP, and iPTH from the control group to patients with AVS, and with reverse changes for 25-OHD levels (all P

The chemorepellent semaphorin-3A (Sema3A) was shown to favor bone metabolism in mice, but its bone effects in humans are not described.The aim of the study was to investigate the associations between serum Sema3A, bone biochemical markers, and bone mineral densities (BMDs) in women.This was a cross-sectional study involving 1012 pre- and postmenopausal women.Fasting serum Sema3A, osteocalcin (Ocn), and cross-linked C-telopeptide of type 1 collagen were measured. Dual-energy X-ray absorptiometry was performed to determine the BMDs at the lumbar spine and femoral neck. History of osteoporotic fractures was reported by the participants.In postmenopausal women (n = 860), a significant positive association between Sema3A and Ocn levels was demonstrated (r = 0.077, P = 0.025) when age was adjusted. The serum Ocn level was significantly higher in the fourth quartile of serum Sema3A as compared with the first quartile (21.09 ± 0.56 ng/mL vs 19.45 ± 0.44 ng/mL, P = .018). Serum Sema3A concentrations were similar in subjects with normal BMD, osteopenia or osteoporosis, and those with and without osteoporotic fractures. Multivariate stepwise regression analysis revealed that cross-linked C-telopeptide of type 1 collagen, body mass index, creatinine, Sema3A, L1-4 BMDs, and age were determinants of Ocn (adjusted R(2) for the model = 0.532, P.001) .The positive correlation between Sema3A and bone formation marker Ocn revealed in this human study partly supports the recently findings in mice studies. However, the general effects of Sema3A on bone metabolism are weak and not clear as evidenced by lack of association between this parameter and BMDs and osteoporotic fractures.

Prolonged isolated thrombocytopenia (PT) is a serious complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT). Murine studies and in vitro experiments suggest that mesenchymal stem cells (MSCs) can, not only to support haematopoiesis, but also preferentially support megakaryocytopoiesis in bone marrow (BM). However, little is known about the quantity and function of BM MSCs in PT patients. In a case-control study, we found that BM MSCs from PT patients exhibited significantly reduced proliferative capacities, increased reactive oxygen species and senescence. Antioxidant (N-acetyl-L-cysteine, NAC) treatment in vitro not only quantitatively and functionally improved BM MSCs derived from PT patients through down-regulation of the p38 (also termed MAPK14) and p53 (also termed TP53) pathways but also partially rescued the impaired ability of BM MSCs to support megakaryocytopoiesis. Subsequently, a pilot study showed that the overall response of NAC treatment was obtained in 7 of the enrolled PT patients (N = 10) without significant side effects. Taken together, the results indicated that dysfunctional BM MSCs played a role in the pathogenesis of PT and the impaired BM MSCs could be improved by NAC in vitro. Although requiring further validation, our data indicate that NAC might be a potential therapeutic approach for PT patients after allo-HSCT.

Background As one of the major treatment obstacles in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL), relapse of Ph+ALL may result from the persistence of leukemia-propagating cells (LPCs). Research using a xenograft mouse assay recently determined that LPCs were enriched in the CD34+CD38−CD58− fraction in human Ph+ALL. Additionally, a cohort study demonstrated that Ph+ALL patients with a LPCs phenotype at diagnosis exhibited a significantly higher cumulative incidence of relapse than those with the other cell phenotypes even with uniform front-line imatinib-based therapy pre- and post-allotransplant, thus highlighting the need for novel LPCs-based therapeutic strategies. Methods RNA sequencing (RNA-Seq) and real-time quantitative polymerase chain reaction (qRT-PCR) were performed to analyze the gene expression profiles of the sorted LPCs and other cell fractions from patients with de novo Ph+ALL. In order to assess the effects of the selective BCR–ABL and/or Janus kinase (JAK)2 inhibition therapy by the treatment with single agents or a combination of ruxolitinib and imatinib or nilotinib on Ph+ALL LPCs, drug-induced apoptosis of LPCs was investigated in vitro, as well as in vivo using sublethally irradiated and anti-CD122-conditioned NOD/SCID xenograft mouse assay. Moreover, western blot analyses were performed on the bone marrow cells harvested from the different groups of recipient mice. Results RNA-Seq and qRT-PCR demonstrated that JAK2 was more highly expressed in the sorted LPCs than in the other cell fractions in de novo Ph+ALL patients. Combination treatment with a selective JAK1/JAK2 inhibitor (ruxolitinib) and nilotinib more effectively eliminated LPCs than either therapy alone or both in vitro and in humanized Ph+ALL mice by reducing phospho-CrKL and phospho-JAK2 activities at the molecular level. Conclusions In summary, this pre-clinical study provides a scientific rationale for simultaneously targeting BCR–ABL and JAK2 activities as a promising anti-LPCs therapeutic approach for patients with de novo Ph+ALL.

Much attention has been focused on the applications of the passive multistatic radar due to its numerous advantages. A linear combination framework for target detection in the passive multistatic radar is proposed here to improve the detection performance. In our framework, the individual test statistics are computed through cross-correlation, then these test statistics from spatially separated receivers are linearly combined to get global decision. A modified deflection coefficient is employed as an optimization criterion for the selection of the weighting coefficients. Particularly, the weighting coefficients are given in closed form which is computationally efficient to calculate. Simulation results illustrate that the proposed approach outperforms its counterparts.

Dopaminergic neuronal injury in the substantia nigra (SN) is a pathological hallmark of Parkinson's disease (PD). However, the underlying mechanism of this injury remains elusive. Since fibroblast growth factor 18 (FGF18) is involved in midbrain development and has been reported to protect neurons from ischemic injury, we investigated whether FGF18 exerted a protective effect on dopaminergic neurons in the SN. In vitro data showed that FGF18 significantly ameliorated the neurotoxicity of 6-hydroxydopamine (6-OHDA) through the AKT/GSK3β signaling pathway. Further study of the 6-OHDA-induced PD rat model indicated that FGF18 improved the behavioral dysfunction in PD rats and reduced the tyrosine hydroxylase (TH)-positive neuronal loss in the SN. In addition, 6-OHDA induced a loss of TH-positive fibers that was reversed by pretreatment with FGF18. Taken together, these data suggest that FGF18 plays a protective role against parkinsonian neurodegeneration in the nigrostriatal system in a 6-OHDA-induced PD rat model and that further drug discovery based on FGF18 has a potential role for PD therapy.

This paper introduces one ultrasonic distance measurement device based on single chip processor and mainly describes its hardware circuit and software design. The ultrasonic distance measurement device has many merits such as simple structure, low-cost, high-accuracy, microminiaturization, digital display and so on; this result reaches the expected target. The practice result shows that the ultrasonic telemeter has very high generalizing value.

In the sustainable development of private universities, stable teachers team is the guarantee of talent training. For colleges or universities, it has important significance to analysis the main factors which cause teachers loss.C4.5 algorithm is a kind of machine learning algorithm in the classification decision tree algorithm. Decision tree is the main technology of data mining classification and prediction. Through the survey data from the information, it establishes the teacher turnover tendency decision tree model using C4.5 algorithm to provide the decision-making basis for the university management work.

Climate change resulted in changes in crop growth duration and planting structure, northward movement of planting region, and more severe plant diseases and insect pests in Northwest China. It caused earlier seeding for spring crop, later seeding for autumn crop, accelerated crop growth, and reduced mortality for winter crop. To adapt to climate change, measures such as optimization of agricultural arrangement, adjustment of planting structure, expansion of thermophilic crops, and development of water-saving agriculture have been taken. Damaging consequences of imbalance between grassland and livestock were enhanced. The deterioration trend of grassland was intensified; both grass quantity and quality declined. With overgrazing, proportions of inferior grass, weeds and poisonous weeds increased in plateau pastoral areas. Returning farmland to grazing, returning grazing to grassland, fence enclosure and artificial grassland construction have been implemented to restore the grassland vegetation, to increase the grassland coverage, to reasonably control the livestock carrying capacity, to prevent overgrazing, to keep balance between grassland and livestock, and to develop the ecological animal husbandry. In Northwest China, because the amount of regional water resources had an overall decreasing trend, there was a continuous expansion in the regional land desertification, and soil erosion was very serious. A series of measures, such as development of artificial precipitation (snow), water resources control, regional water diversion, water storage project and so on, were used effectively to respond to water deficit. It had played a certain role in controlling soil erosion by natural forest protection and returning farmland to forest and grassland. In the early 21st century, noticeable achievements had been made in prevention and control of desertification in Northwest China. The regional ecological environment has been improved obviously, and the desertification trend has shown sign of under control. Citation Zhao, H.-Y., J.-Q. Guo, C.-J. Zhang, et al., 2014: Climate change impacts and adaptation strategies in Northwest China. Adv . Clim . Change Res ., 5 (1), doi: 10.3724/SP.J.1248.2014.007.

Background: Bone marrow(BM) endothelial cells(ECs), a key component of BM microenvironment, is essential for the physiology and regeneration of hematopoietic stem cells (HSCs). The damage of ECs is recognized by us and other researchers as a mainstay in the pathophysiology of a serious of life-threatening complications after chemoradiotherapy and myeloablative hematopoietic cell transplantation(HSCT), including poor graft function (PGF) (2013BBMT, 2015BMT, 2016Blood, 2019Blood Advances). Despite numerous researches focused on the BM ECs contributing to HSC regeneration following myelotoxicity, the mechanisms underlying the injured BM ECs itself remain to be elucidated. Under physiological conditions, energy metabolism plays an instrumental role in maintaining EC function, and markedly perturbed of EC metabolism is linked to many pathologies, like cancer and diabetes. However, little is known about the metabolism state and its role in impaired BM ECs. Aims: The current study was performed to investigate the metabolism status in BM ECs after chemotherapy-induced injury. Moreover, we evaluated the metabolic state and its role in BM ECs of PGF patients post-allotransplant. Finally, we evaluated the therapeutical potential of anti-metabolic drugs to the dysfunctional BM ECs derived from PGF patients. Methods: Two EC injury models in vitro were established with the cultivated human BM ECs treated by 5-Fluorouracil (5-FU) and hydrogen peroxide. The findings from the above models were further validated by a prospective case-control study enrolled 15 patients with PGF, 30 matched patients with good graft function (GGF) and 15 healthy donors (HD). To determine the metabolic status of BM ECs, the expression of metabolism regulating genes was analyzed by qRT-PCR (mRNA level) and flow cytometry (protein level). Glucose metabolism levels were measured by glucose consumption and lactate production assays. To evaluate the functions of BM ECs, apoptosis, migration and tube formation assays were performed. To investigate the effect of anti-metabolic drugs to injured BM ECs, the glycolysis inhibitor 3PO and PPARd agonist GW501516 were administrated to the cultivated BM ECs treated by 5-FU , hydrogen peroxide or derived from PGF. Results: We demonstrated that the glycolysis in BM ECs could be induced by the treatment with either 5-FU or hydrogen peroxide in vitro, consistent with the dysfunction(impaired migration, angiogenesis, and higher level of apoptosis) of BM ECs, which could be attenuated by glycolysis restoration. Mechanistically, we revealed that the aberrant glycolysis and dysfunction of BM ECs could be triggered by PPARd knockdown in vitro, while the PPARd were down-regulated by either 5-FU or hydrogen peroxide treatment in vitro, Furthermore, PPARd agonist GW501516 treatment attenuated the perturbed function and number of injured BM ECs treated by either 5-FU or hydrogen peroxide. Subsequently, the prospective case-control study demonstrated elevated expressions of the glycolytic activator PFKFB3 and decreased PPARd were observed in BM ECs of PGF patients, when compared with those of GGF patients and HD, indicating that BM ECs of PGF patients have a hyper-glycolytic metabolism. Moreover, either glycolysis (PFKFB3) inhibitor 3PO or PPARd agonist GW501516 treatment reduced the aberrant glycolysis and improved the number and function of BM ECs derived from patients with PGF in vitro, revealing the critical role of defective glycolysis in the impaired BM ECs of PGF. Summary / Conclusions: These findings reveal that hyper-glycolysis mediated by PPARd inhibition is involved in the dysfunction of BM ECs after injury. Defective glycolysis may contribute to the pathobiology of BM ECs of PGF patients, which could be attenuated by glycolysis inhibitor 3PO or PPARd agonist GW501516 in vitro. Our findings might merit further consideration of targeting BM ECs glycolysis or PPARd as a promising therapeutic approach for PGF patients post-allotransplant in the future. Disclosures No relevant conflicts of interest to declare.

In order to solve the confinement problem of liquid metal, permanent magnet sealing is discussed in this paper, and its principle is introduced. Based on calculations, some helpful conclusions are made, which are important for research on hot dip galvanizing process without sink roll.

Based on weighted grey relational analysis, a new failure diagnosis method for complicated electronic equipments is proposed. First, according to the typical failure samples and weight values to construct grey reference sequence. Secondly, calculating the individual relational coefficient and grade to form grey relational grade sequence. Finally, according to the maximal grey relational grade to choose the corresponding failure mode as the finally diagnosis result. The results of analyses show that the proposed method has higher diagnosis accuracy and reliability than the traditional grey relational method.

In the 1970s, with the advent of biochemical multichannel screening in the United States and other western countries, the clinical presentation of primary hyperparathyroidism (PHPT) changed from a symptomatic to an asymptomatic disorder. However, in Asian countries, like China, PHPT did not show this evolution, but rather continued to be a symptomatic disease with target organ involvement. In this paper, we revisit the clinical features of PHPT in New York and Shanghai, representative United States and Chinese cites, over the past decade. The questions we address are whether the disease evolved in China to a more asymptomatic one and, whether in the United States further changes are evident. The results indicate that while PHPT continues to present primarily as an asymptomatic disease in the United States, a new phenotype characterized by normal serum calcium and high parathyroid hormone levels, normocalcemic PHPT, has emerged. Data from Shanghai demonstrates a trend for PHPT to present more commonly as an asymptomatic disorder in China. However, most patients with PHPT in China still manifest classical symptoms, i.e. nephrolithiasis and fractures. A comparison of the two cohorts shows that Chinese patients with PHPT are younger, with higher serum calcium and PTH levels, and lower 25-hydroxyvitamin D levels than patients in New York. Normocalcemic PHPT has not yet been recognized in Shanghai. In summary, although the phenotypes of PHPT in both cities are evolving towards less evident disease, sharp clinical and biochemical differences are still apparent in PHPT as expressed in China and the United States.

Based on increasing evidence from animal and human studies, vitamin D deficiency is now regarded as a potential risk factor for Type 2 diabetes mellitus (T2DM). Vitamin D is involved in the pathogenesis of pancreatic β-cell dysfunction, insulin resistance, and systemic inflammation, conditions that contribute to the development of T2DM. Vitamin D can affect the progress of this disease directly through the activation of its own receptor, and indirectly via the regulation of calcium homeostasis. Observational studies have revealed the association between vitamin D deficiency and incident T2DM. More double-blind randomized control studies that investigate the effects of vitamin D supplementation on insulin sensitivity, insulin secretion, and the occurrence of T2DM are needed.

SummaryBackground The relationships between quantitative ultrasound (QUS) values, metabolic syndrome (MetS) and cardiovascular disease (CVD) risk are unclear. Objective The objective was to determine the relationships between QUS and MetS as well as CVD risk. Design This was a cross-sectional study conducted in Shanghai, China. Patients One-thousand four hundred and thirty-nine Chinese women and men with or without MetS were studied. Measurements Speed of sound (SOS) at radius, phalanx and tibia and their relationships with MetS and Framingham's 10-year cardiovascular disease risk scores were investigated. Results Premenopausal women with MetS had significant lower SOS at radius than those without MetS after adjusting for age, BMI and fat mass percentage (P = 0·02). The radius SOS was negatively associated with waist circumference (r = −0·109, P = 0·025), waist-to-hip ratio (r = −0·124, P = 0·01) and 2 h postprandial glucose level (r = −0·125, P = 0·012) in premenopausal women. Waist circumference, waist-to-hip ratio and 2 h postprandial glucose level increased with the decreasing tertiles of radius SOS after adjustment of age (P = 0·003, 0·002 and 0·008, respectively). The CVD risk increased with decreasing tertiles of radius SOS in postmenopausal women even after the adjustment of age, years since menopause, MetS components, smoking and alcohol habits (P

To discuss the flying cutter used in PS plate production line.From mechanical and control two aspects to optimization improvement, in order to adapt to the cutting requirements. For new control scheme, in the theoretical derivation and actual operation were introduced, the new scheme in the actual operation of the encountered problems were analyzed, and the method of solution to meet the Plate material. Through the practical application and theoretical checking, proves the validity and feasibility of the scheme.

Femtosecond laser with the features of ultrashort pulse duration and ultrahigh peak power can achieve “cold” machining. The recast layer and micro-cracks of the hole wall can be ruduced effectively by applying femtosecond laser in processing air-film holes on turbine blades, and the machining accuracy and consistency of the hole shape will increase. In this paper, the high-speed rotating femtosecond laser beam is adopted in several currently used turbine blade materials for air-film holes machining, and high quality air-film holes without hole wall recast layer and micro-cracks are processed through a large number of experiments to optimize machining technology and technological parameter.

Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare, autosomal recessive genetic disease. This disease is characterized by the progressive calcification of soft tissues leading to symptoms of pressure and hyperphosphatemia but normal concentrations of serum calcium with or without an elevation of 1,25-dihydroxyvitamin D3 levels.HFTC is caused by loss-of-function mutations in the GALNT3, FGF23 or KL genes. Here, we identified two novel mutations in the GALNT3 gene in a Chinese family with HFTC. Identification of a novel genotype in HFTC provides clues for understanding the phenotype–genotype relationships in HFTC and may assist not only in the clinical diagnosis of HFTC but also in the interpretation of the genetic information used for prenatal diagnosis and genetic counseling. Two new mutations have been linked to a rare disease characterized by abnormal deposits of phosphate and calcium. Hyperphosphatemic familial tumoral calcinosis (HFTC) results from an increase in the levels of phosphate in the blood and a progressive calcification of the soft tissues around joints, most often in the hips, shoulders and elbows. The calcium deposits can form masses that impair movement. A team led by Jianmin Liu and Xiaoyi Ding from the Shanghai Jiao-Tong University School of Medicine, China, describe two novel mutations in a gene called GALNT3 in a pair of Chinese siblings with HFTC. These findings, the first from a Chinese family clinically diagnosed with HFTC and confirmed by genetic analysis, should help in future diagnoses and in understanding the molecular causes of the disease.

Bone is an endocrine organ involved in modulating glucose homeostasis. The role of the bone formation marker osteocalcin (OCN) in predicting diabetes was reported, but with conflicting results. No study has explored the association between baseline bone resorption activity and incident diabetes or prediabetes during follow-up. Our objective was to examine the relationship between the baseline bone resorption marker crosslinked C-telopeptide of type I collagen (CTX) and glycemic dysregulation after 4 years. This longitudinal study was conducted in a university teaching hospital. A total of 195 normal glucose tolerant (NGT) women at baseline were invited for follow-up. The incidence of diabetes and prediabetes (collectively defined as dysglycemia) was recorded. A total of 128 individuals completed the 4-year study. The overall conversion rate from NGT to dysglycemia was 31.3%. The incidence of dysglycemia was lowest in the middle tertile [16.3% (95% confidence interval (CI), 6.8%–30.7%)] compared with the lower [31.0% (95% CI, 17.2%–46.1%)] and upper [46.5% (95% CI, 31.2%–62.6%)] tertiles of CTX, with a significant difference seen between the middle and upper tertiles (P=0.002 5). After adjusting for multiple confounding variables, the upper tertile of baseline CTX was associated with an increased risk of incident dysglycemia, with an odds ratio of 7.09 (95% CI, 1.73–28.99) when the middle tertile was the reference. Osteoclasts actively regulate glucose homeostasis in a biphasic model that moderately enhanced bone resorption marker CTX at baseline provides protective effects against the deterioration of glucose metabolism, whereas an overactive osteoclastic function contributes to an increased risk of subsequent dysglycemia.

Accumulating evidence suggests that oxidative stress is associated with osteoporosis. Serum uric acid (UA) is a strong endogenous antioxidant. Therefore, we investigated the relationship between the serum UA and BMD in Chinese men with T2DM. In this cross-sectional study of 621 men with T2DM, BMDs at lumbar spine (L2–4), femoral neck (FN), and total hip (TH) were measured by dual-energy X-ray absorptiometry (DXA). Serum levels of UA, calcium (Ca), 25-OH vitamin D3 (vitD3), parathyroid hormone (PTH), and creatinine (Cr) were also tested. Data analyses revealed that serum UA levels were positively associated with BMD at all sites (p<0.05) in men with T2DM after adjusting for multiple confounders. The serum UA levels were positively correlated with body weight (r=0.322), body mass index (BMI) (r=0.331), Ca (r=0.179), and Cr (r=0.239) (p<0.001) and were also positively associated with the concentrations of PTH (r=0.10,p<0.05). When compared with those in the lowest tertile of UA levels, men with T2DM in the highest tertile had a lower prevalence of osteoporosis or osteopenia (adjusted odds ratio 0.54, 95% confidence interval [CI] 0.31–0.95). These data suggest that higher serum levels of UA are associated with higher BMDs and lower risks of osteoporosis in Chinese men with T2DM.

To investigate the effects of genetic and non-genetic factors on bone mineral densities (BMDs) and osteoporotic fractures. This was a cross-sectional study to investigate the relationships between 18 SNPs and non-genetic factors with BMDs and osteoporotic fractures in 1012 Chinese Han women. Five SNPs in genes GPR177, CTNNB1, MEF2C, SOX6, and TNFRSF11B were associated with L1-4 or total hip BMDs. rs11898505 in SPTBN1 gene was associated with osteoporotic fractures. Subjects carrying the largest number of risk alleles (highest 10 %) not only had lower BMD values as compared to those carrying the least number of risk alleles (lowest 10 %), they also had a higher risk of fracture [P = 0.002, OR = 2.252, 95 %CI (1.136, 4.463)]. Results from multivariate stepwise regression analysis revealed that age [P < 0.001, OR = 1.038, 95 % CI (1.018, 1.058)], number of falls in a year [P < 0.001, OR = 2.347, 95 % CI (1.459, 3.774)], the G risk allele in rs11898505 [P = 0.023, OR = 1.559, 95 % CI (1.062, 2.290)], and the L1-4 BMD [P = 0.017, OR = 0.286, 95 % CI (0.102, 0.798)] were associated with the occurrence of osteoporotic fractures. Genetic (rs11898505) and non-genetic factors (age, number of falls in a year and L1-4 BMD) could work in concert to contribute to the risk of osteoporotic fractures.