[A randomized double-blinded placebo-controlled clinical trial of minodronate tablet in postmenopausal Chinese women with osteoporosis].

Objective: To verify the efficacy and safety of daily oral minodronate in postmenopausal women with established osteoporosis. Methods: In this randomized, double-blinded, placebo-controlled trial, 262 postmenopausal women were enrolled. Patients were randomized to receive daily oral minodronate 1 mg with supplements of 500 mg calcium and 200 U vitamin D3 (n=130) or placebo (n=132) with daily supplements of 500 mg calcium and 200 U vitamin D3, for 48 weeks. The primary endpoint was the average bone mineral density (BMD) change in the lumbar vertebrae 48 weeks post-treatment. Secondary outcome measures was the incidence of vertebral fractures. Safety assessments included the rate of adverse events. Results: At the end of 48 weeks treatment, the average BMD change rate from baseline were: full analysis set results: (3.52±4.82)% in the minodronate group and (2.00±5.74)% in the placebo group; per-protocol set results: (3.99±5.05)% in the minodronate group and (2.07±6.20)% in the placebo group; the differences were all significant (all P<0.05). Vertebral fracture occured in 3 patients (2.3%, 3/132) in the placebo group, and 1 case (0.8%, 1/130) in the minodronate group (P>0.05). The incidence of adverse events was 71.5% (93/130) in the minodronate group and 78.0% (103/132) in the placebo group (P>0.05). Conclusion: Minodronate is effective and safe in the treatment of postmenopausal osteoporosis without severe side effects.

Correlations of 25(OH)D level with blood lipid, inflammatory factors and vascular endothelial function in diabetic patients.

OBJECTIVE: To investigate the correlation between 25-hydroxyvitamin D [25(OH)D] and the lipid profile, inflammatory cytokines, and endothelial function in diabetic patients. PATIENTS AND METHODS: A total of 77 patients with type 2 diabetes mellitus treated in our hospital from January 2015 to March 2017 and 73 healthy volunteers were selected. The 25(OH)D, lipids, inflammatory factors, and endothelial function were compared between the two groups. The levels of 25(OH)D in diabetic patients were also compared to detect the levels of serum lipids and inflammatory cytokines in different groups. According to the inflammatory factors, patients with diabetes mellitus were divided into several groups. In addition, 25(OH)D, endothelial function indicators [nitrogen oxide (NO) and von Willebrand factor (vWF)], serum lipids [triglyceride (TG) and total cholesterol (TC)], high-density lipoprotein (HDL), and inflammatory factor tumor necrosis factor-alpha (TNF-α) were compared among different groups. RESULTS: Compared with normal group, the 25(OH)D, NO, and HDL in the diabetic group were significantly lower than those in the normal group (p<0.05). Other lipids and inflammatory factors in the former were significantly higher than those in the normal group. Patients have lower HDL in those with less amount of 25(OH)D. Other blood lipid components such as TC and TG, LDL, and inflammatory factors significantly increased gradually as the 25(OH)D grows (p<0.05). For patients with more inflammatory cytokines, levels of 25(OH)D, NO, vWF, and ET-1 were significantly lower than those with normal inflammatory cytokines. Correlation analysis revealed that 25(OH)D was positively correlated with HDL and NO, but negatively correlated with TG, TC, TNF-α, and vWF. CONCLUSIONS: In diabetic patients, the level of 25(OH)D is decreased and the inflammatory factors are increased. In patients with proper supplementation of 25(OH)D, the inflammation can be reduced and endothelial function can be improved.

Icariin may benefit the mesenchymal stem cells of patients with steroid-associated osteonecrosis by ABCB1-promoter demethylation: a preliminary study.

UNLABELLED: In this study, we found out a previously undefined function of icariin which restored the dynamic balance between osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs) in patients with osteonecrosis of femoral head (ONFH) via ABCB1-promoter demethylation. These findings provided important information regarding potential implication of icariin targeting epigenetic changes for the treatment of steroid -associated ONFH. INTRODUCTION: Here, we investigated whether icariin can also exert a beneficial role in the reactivation of MSCs in the patients with steroid-associated ONFH via ABCB1-promoter demethylation. METHODS: Bone marrow was collected from the proximal femur in patients with steroid-associated ONFH (n = 20) and patients with new femoral neck fractures (n = 22), and then MSCs were isolated. We investigated cell viability, intracellular reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP), P-glycoprotein (P-gp) activity, the transcript levels of ABCB1 and oxidative stress-related genes, methylation extent at CpG islands of ABCB1 promoter, and osteogenic and adipogenic differentiation ability of MSCs from the femoral neck fractures group and from the steroid-associated ONFH group treated with or without icariin. RESULTS: We observed that MSCs from the steroid-associated ONFH group showed reduced proliferation ability, elevated ROS level, depressed MMP, weakened osteogenesis, and enhanced adipogenesis while low P-gp activity, transcription level of ABCB1, and oxidative stress-related genes as well as aberrant CpG islands hypermethylation of ABCB1 were also noted in steroid-associated ONFH group. Treatment with icariin obviously induced de novo P-gp expression, decreased oxidative stress, and promoted osteogenesis. CONCLUSION: Icariin may be a potential drug targeting epigenetic changes for the treatment of steroid-associated ONFH.

GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib): second interim analysis.

BACKGROUND: GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma [HCC] and Of its treatment with sorafeNib) is a global, prospective, non-interventional study undertaken to evaluate the safety of sorafenib in patients with unresectable HCC in real-life practice, including Child-Pugh B patients who were excluded from clinical trials. METHODS: Patients with unresectable HCC, for whom the decision to treat with sorafenib, based on the approved label and prescribing guidelines, had been taken by their physician, were eligible for inclusion. Demographic data and disease/medical history were recorded at entry. Sorafenib dosing and adverse events (AEs) were collected at follow-up visits. The second interim analysis was undertaken when ~1500 treated patients were followed up for ≥ 4 months. RESULTS: Of the 1571 patients evaluable for safety, 61% had Child-Pugh A status and 23% Child-Pugh B. The majority of patients (74%) received the approved 800 mg initial sorafenib dose, regardless of Child-Pugh status; however, median duration of therapy was shorter in Child-Pugh B patients. The majority of drug-related AEs were grade 1 or 2, and the most commonly reported were consistent with previous reports. The incidence and nature of drug-related AEs were broadly similar across Child-Pugh, Barcelona Clinic Liver Cancer (BCLC) and initial dosing subgroups, and consistent with the overall population. CONCLUSIONS: Consistent with the first interim analysis, overall safety profile and dosing strategy are similar across Child-Pugh subgroups. Safety findings also appear comparable irrespective of initial sorafenib dose or BCLC stage. Final analyses in > 3000 patients are ongoing.

Projection patterns of lateral hypothalamic, cocaine- and amphetamine-regulated transcript (CART) neurons to the dorsal raphe and/or the locus coeruleus in the rat.

The present study was designed to reveal the projection patterns of lateral hypothalamic (LH), cocaine- and amphetamine-regulated transcript (CART) neurons to the dorsal raphe (DR) and/or the locus coeruleus (LC) in the rat. After the injection of Red or Green Retrobeads into the DR or LC, LH sections were immunostained for CART and/or melanin-concentrating hormone (MCH). First, CART-immunoreactive axon terminals formed close appositions to the DR (or LC) neuronal profiles. Second, a subpopulation of CART neurons containing MCH projected to the monoaminergic nuclei; the majority of labeled neurons were observed in the dorsal hypothalamic area, the dorsal part of the posterior hypothalamic area, and the zona incerta. Cells were also observed in the perifornical part of the LH, the dorsomedial hypothalamic nucleus, the peduncular and the magnocellular parts of the LH. Of the total population of DR (or LC)-projecting cells, CART/MCH co-containing neurons were 9.5% ± 1.6% (or 10.8% ± 1.3% for LC). Finally, a subset of CART (or MCH) neurons provided divergent axon collaterals to the DR and the LC. Of the entire CART (or MCH) cell population, 3.9% ± 0.8% (or 5.6% ± 1.0% for MCH) sent axon collaterals to the DR/LC. CART/MCH co-containing neurons projecting to the DR or LC might be involved in the feeding-related regulation of arousal, stress-related responses, and emotional behaviors. Thus, CART (or MCH) cells that send divergent axon collaterals to the DR/LC might have a simultaneous (and possibly more efficient) way to exert their specific influences on the aminergic nuclei.

First interim analysis of the GIDEON (Global Investigation of therapeutic decisions in hepatocellular carcinoma and of its treatment with sorafeNib) non-interventional study.

AIMS: Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib (GIDEON), a global, non-interventional, surveillance study, aims to evaluate the safety of sorafenib in all patients with unresectable hepatocellular carcinoma (uHCC) under real-life practice conditions, particularly Child-Pugh B patients, who were not well represented in clinical trials. METHODS: Treatment decisions are determined by each physician according to local prescribing guidelines and clinical practice. Patients with uHCC who are candidates for systemic therapy, and for whom a decision has been made to treat with sorafenib, are eligible for inclusion. Demographic data and medical and disease history are recorded at entry. Sorafenib dosing and adverse events (AEs) are collected throughout the study. RESULTS: From January 2009 to April 2011, >3000 patients from 39 countries were enrolled. The prespecified first interim analysis was conducted when the initial approximately 500 treated patients had been followed up for ≥4 months; 479 were valid for safety evaluation. Preplanned subgroup analyses indicate differences in patient characteristics, disease aetiology and previous treatments by region. Variation in sorafenib dosing by specialty are also observed; Child-Pugh status did not appear to influence the starting dose of sorafenib. The type and incidence of AEs was consistent with findings from previous clinical studies. AE profiles were comparable between Child-Pugh subgroups. DISCUSSION: The GIDEON study is generating a large, robust database from a broad population of patients with uHCC. First interim analyses have shown global and regional differences in patient characteristics, disease aetiology and practice patterns. Subsequent planned analyses will allow further evaluation of early trends.

Effects of copper-loaded chitosan nanoparticles on growth and immunity in broilers.

Effects of dietary copper-loaded chitosan nanoparticle (CNP-Cu) supplementation on growth performance, hematological and immunological characteristics, and the cecal microbiota in broilers were investigated. Three hundred healthy Avian × Avian (1-d-old) broilers were randomly assigned into 5 dietary groups (20 birds per replicate with 3 replicates per group). Birds were fed with 0 (the control group), 50, 100, 150 mg/kg of CNP-Cu and 50 mg/kg chlorotetracycline (CTC, a positive control group) for 42 d. Results indicated that supplemental CNP-Cu could improve growth performance, affect the immune system, enhance protein synthesis, and be beneficial to cecal microbiota of Avian broilers, especially the dietary supplementation with 100 mg/kg of CNP-Cu. Supplementation with 100 mg/kg of CNP-Cu increased the average daily gain(P < 0.05) and the contents of IgA (P < 0.01), IgG (P < 0.01), IgM (P < 0.01), complement C3 (P < 0.05), and complement C4 (P < 0.05). Thymus, spleen, and bursa of Fabricus indexes and the populations of Lactobacillus and Bifidobacterium in cecal digesta were increased (P < 0.05) by 100 mg/kg of CNP-Cu supplementation, and the population of coliforms was decreased (P < 0.05). Dietary supplementation with 100 mg/kg of CNP-Cu increased (P < 0.05) concentrations of serum total protein and albumin, and decreased (P < 0.05) the content of urea nitrogen in serum. Effects of dietary supplementation with 100 mg/kg of CNP-Cu were similar to 50 mg/kg of CTC supplementation. These results may indicate that CNP-Cu could be a new substitute for CTC in dietary supplementation.

Design and rationale for the non-interventional Global Investigation of Therapeutic DEcisions in Hepatocellular Carcinoma and Of its Treatment with Sorafenib (GIDEON) study.

BACKGROUND: Hepatocellular carcinoma (HCC) is a complicated condition influenced by multiple confounding factors, making optimum patient management extremely challenging. Ethnicity, stage at diagnosis, comorbidities and tumour morphology affect outcomes and vary from region to region, and there is no common language to assess patient prognosis and make treatment recommendations. Despite recent efforts to reduce the incidence of HCC, most patients present with unresectable disease. Non-surgical treatments include ablation, transarterial chemoembolisation and the multikinase inhibitor, sorafenib, but their effects in all patient subgroups are not known and further information is needed to optimise the use of these treatments. AIMS: The Global Investigation of Therapeutic DEcisions in Hepatocellular Carcinoma and Of its Treatment with SorafeNib (GIDEON) study (ClinicalTrials.gov identifier NCT00812175; http://clinicaltrials.gov/) is an ongoing global, prospective, non-interventional study of patients with unresectable HCC who are eligible for systemic therapy and for whom the decision has been taken to treat with sorafenib under real-life practice conditions. The aim of this study is to evaluate the safety and efficacy of sorafenib in different subgroups, especially Child-Pugh B where data are limited. DISCUSSION: This study will recruit 3000 patients from > 40 countries and follow them for approximately 5 years to compile a large and robust database of information that will be used to analyse local, regional and global differences in baseline characteristics, disease aetiology, treatment practice patterns and treatment outcomes, with a view to improve the knowledge base used to guide physician treatment decisions and to improve patient outcomes.

Renoprotective effect of rosiglitazone through the suppression of renal intercellular adhesion molecule-1 expression in streptozotocin-induced diabetic rats.

OBJECTIVE: To observe the effect of rosiglitazone on serum intercellular adhesion molecule-1 (SICAM-1) level, urinary excretion of ICAM-1, and renal expression of ICAM-1, and investigate its possible renoprotective mechanisms in diabetic rats. METHOD: Twenty-four Wistar Rats were divided into 3 groups: non-diabetic control rats (group A, no.=8), streptozotocin-induced diabetic rats (group B, no.=8), and diabetic rats treated with rosiglitazone (group C, no.=8). Rats in group C were treated with rosiglitazone (5 mg x kg(-1) x d(-1)) 1 week after the establishment of diabetic model, group A and B were treated with corresponding sodium chloride. Peripheral blood glucose was tested weekly. Glycosylated hemoglobin (HbA1c) and SICAM-1 as well as urinary albumin excretion rate (UAER), urinary retinol binding-protein (URBP) excretion rate, and urinary ICAM-1 (UICAM- 1) excretion rate were tested at the 8th week, and the renal tissues of all rats were obtained for evaluating kidney/body weight ratio, observing pathologic change via electron microscope, and for examining the expression of ICAM-1 mRNA by reverse transcriptase-PCR. RESULTS: At the 8th week, the blood glucose, HbA1c levels, UAER, URBP excretion rate, kidney/body weight ratio and serum, urinary ICAM-1 levels all increased significantly in group B and group C in comparison with group A; however, the above-mentioned parameters in group C (except the blood glucose and HbA1c levels) were much lower than those in group B. In addition, both SICAM-1 and UICAM-1 were highly correlated with the UAER, URBP level, and kidney/body weight ratio in all rats; renal pathological lesions observed by electron microscope in group C were much lighter than those of group B; compared with group A, the expression of ICAM-1 mRNA was markedly up-regulated in group B and group C, and rosiglitazone was able to decrease the expression of ICAM-1 mRNA in the renal tissue. CONCLUSION: Rosiglitazone could definitely protect against the renal injury of diabetic rats, which may be partly associated with decreasing the expression of ICAM-1 in the renal tissue, reducing ICAM-1 productions in both serum and urine.

[Determination of salicin in extract of willow bark by high performance liquid chromatography].

An HPLC method for the determination of salicin in extract of willow bark is described. Chromatographic analysis was carried out on a Kromasil C18, 5 microns column(4.6 mm i.d. x 250 mm) with methanol-0.01 mol/L KH2PO4 buffer (pH 4.01) (15:85, volume ratio) as mobile phase. The detection wavelength was 265 nm. Salicin was extracted from samples with methanol-water(50:50, volume ratio), and centrifuged. Ten microL of supernatant were injected. The average recoveries were from 96.1% to 101.2% (n = 5), and the relative standard deviation (RSD) was 1.43%. The method is simple, rapid and accurate.

miniSAGE: gene expression profiling using serial analysis of gene expression from 1 microg total RNA.

The use of serial analysis of gene expression (SAGE) to determine gene expression profiles is increasing because the technique can provide absolute transcript numbers in a digital format and identify new genes. We developed a miniSAGE technique, which uses only 1 microg total RNA and reduces the amount of the starting material by 250- to 500-fold. Unlike the other modified SAGE methods, the miniSAGE technique does not require the additional PCR amplifications. The additional PCR amplifications potentially introduce bias and compromise the quantitative aspects of the SAGE method. Three key modifications in the miniSAGE technique are: (i) using the phase lock gel (PLG, Eppendorf) to increase the recovery and the purity of DNA material after each phenol extraction step; (ii) reducing the amount of linkers in the ligation, thereby minimizing their interference with SAGE ditag amplification and increasing the SAGE ditag yield; and (iii) employing the mRNA capture kit (Boehringer Mannheim) to allow the first five steps: mRNA isolation, cDNA synthesis, enzyme cleavage of cDNA, binding of the cleaved biotin-cDNA to the streptavidin-magnetic beads, ligating linkers to the bound cDNA, and the release of cDNA tags to occur within one tube to significantly reduce the loss of material between successive steps. Two fibroblast SAGE libraries have been successfully prepared. The preliminary analysis of 3838 tags from one library demonstrated a typical fibroblast gene expression pattern. This miniSAGE technique will permit a broader application of SAGE.

Nitric-oxide-dependent pial arteriolar dilation in the female rat: effects of chronic estrogen depletion and repletion.

In this study, we compared endothelial nitric oxide synthase (eNOS)-mediated cerebral vasodilating responses in intact female rats, chronically ovariectomized (OVX) rats, and OVX rats treated for 2 weeks with 17beta-estradiol (E(2)). Under anesthesia, using intravital microscopy and a closed cranial window system, pial arteriolar diameter changes were monitored during sequential cortical suffusions of an eNOS-dependent dilator [acetylcholine (ACh)] and a direct NO donor [S-nitrosoacetylpenicillamine (SNAP)]. In separate rats from the same groups, we compared eNOS and caveolin-1 (CAV-1) protein abundance in pial arterioles (via immunofluorescence analyses). In untreated and low-dose E(2)-treated (1.0 microg x kg(-1) x day(-1)) OVX rats, ACh-induced vasodilations were virtually absent. High-dose E(2) treatment (100 microg x kg(-1) x day(-1)) restored ACh-induced pial arteriolar dilations to levels seen in intact females. The vasodilations elicited by SNAP and ADO were unaffected by chronic estrogen changes, indicating no direct estrogen influence on vascular smooth muscle (VSM) reactivity. Pial arteriolar eNOS protein abundance was diminished by ovariectomy and restored by high-dose E(2) treatment. Pial arteriolar CAV-1 expression was higher in OVX versus intact and E(2)-treated OVX females. These results suggest that long-term changes in estrogen directly influence brain eNOS functional activity. The estrogen-related changes in eNOS-dependent vasodilating function appear to be related, in part, to a capacity for E(2) to increase eNOS protein expression and, in part, to an E(2)-associated diminution in endothelial CAV-1 expression.

[Investigation on the fruit output and ecological environment of Caesalpinia in China].

OBJECTIVE: To estimate the fruit output of Caesalpinia in China and understand its ecological environment. METHOD: On-the-spot investigation in the producing area. RESULT: The output of 8 species of Caesalpinia was estimated and their ecological environment was described. CONCLUSION: The natural resources of Chinese Caesalpinia, especially C. decapetala and C. minax, are rich, and thus worth exploring and developing.

[Studies on tannin and hydrolysate in three species of Chinese Caesalpinia plants].

OBJECTIVE: To get Chinese Caesalpinia plants that can replace the imported Tara to produce tannin and gallic acid. METHOD: Extract tannin with water, condense and hydrolyze the extracts with alkali, the hydrolysates were identified. Furthermore, an enlarged scale experiment was conducted. RESULT: Tannin contents of the plants were 32.2%, 46.6% and 58.5% respectively, the converted ratios of raw material to hydrolysate were 154:1, 11.8:1, 3.09-2.79:1 respectively. CONCLUSION: We got the Tara-replacing plants in Chinese Caesalpinia plants for the first time.

[Species and distribution of Chinese medicinal plant Caesalpinia].

OBJECTIVE: To gain a clear idea on the resources of medicinal plant Caesalpinia in China. METHOD: Conducting field investigation and consulting related specimens and data. RESULT: The distribution, growing environment and medicinal parts of 14 species of Caesalpinia have been clarified, and a key for their identification is given. CONCLUSION: A scientific basis for further study of the medicinal plant Caesalpinia in China has been provided.

A limited renal injury may cause a permanent form of neurogenic hypertension.

Previously, we have shown that an acute injury to the kidney produced by an intrarenal injection of phenol causes an immediate increase in blood pressure and in norepinephrine (NE) secretion from the posterior hypothalamus. The studies suggest that in this model afferent impulses from the kidney to central integrative structures in the brain may be responsible for the increase in blood pressure. To further evaluate whether a renal injury caused by the intrarenal injection of phenol leads to a permanent elevation of blood pressure and whether this is mediated by increased sympathetic nervous system activity, we examined the chronic effects (4 weeks) of an intrarenal injection of 50 microL of 10% phenol on blood pressure and NE secretion from the posterior hypothalamus. Systolic blood pressure increased from 128 +/- 2.1 to 176 +/- 1.5 mm Hg (P < .01) 4 weeks after receiving the intrarenal injection of phenol, but it did not change in rats that received the vehicle (128 +/- 2.4 and 135 +/- 1.7 mm Hg) and in rats that were subjected to renal denervation (127 +/- 3.4 and 124 +/- 1.0 mm Hg). The secretion of NE from the posterior hypothalamic nuclei was greater (P < .01) in rats that received phenol (253 +/- 9.6 pg/mL) than in controls (158 +/- 8.6 pg/mL) and denervated rats (170 +/- 2.1 pg/mL). These studies have shown that a limited injury to one kidney may cause a permanent elevation of blood pressure and this is associated with increased sympathetic nervous system activity.

[An ELISA assay for humulus scandens specific IgE antibodies].

OBJECTIVE: Humulus scandens pollen (HSP) has been proved to be the one of the most important causative factors of autumnal hay fever in China. We established an enzyme immunoassay for specific IgE against HSP by using monoclonal anti-IgE antibody to detect sIgE in 143 patients with autumnal hay fever and 30 healthy volunteers. METHODS: An indirect method of ELISA was developed. The optimal conditions for the test were: coating the allergen at 4 degrees C overnight with a concentration of 12 micrograms/ml; the test serum was diluted 1:16 and incubated with allergen overnight at 37 degrees C; the most suitable dilution and incubative time of the peroxidase-conjugated mouse anti-human IgE antibody were 1:3,000 and 2 hours respectively. RESULTS: The patients' serum level of sIgE was significantly higher than controls (P < 0.001) and correlated significantly with the degree of skin test reaction (P < 0.01). The concordance between the results of skin test and ELISA was 74%-83%. The specificity of the assay was confirmed by heat inactivation and multiple absorption experiments. The coefficients of variation for the intraassay and interassay reproducibility ranged from 1.20%-8.30% and 8.63%-9.22% respectively. CONCLUSIONS: Determination of specific HSP IgE with ELISA assay shows good specificity, sensitivity and reproducibility. It favours clinical practice due to its lower cost.

The effect of sheng bai solution on irradiated mice bone marrow cell division index and DNA content.

Before and after general irradiation with 60Co-gamma, mice were orally given Sheng Bai Solution (SBS) for one week. SBS alleviated the irradiation-induced reduction of bone marrow cell chromosome division index. The irradiation-induced decrease of marrow DNA amount, thymic and splenic fractions, and total leukocyte number were restored to some extent. SBS also helped to ameliorate general condition of patients.

[Morphological characteristics of fruits and seeds of Chinese Caesalpinia and its taxonomic significance].

OBJECTIVE: To set up a toxonomic approach to the morphological characteristics of fruits and seeds of Chinese Caesalpinia. METHOD: The ripe fruits collected in the field are dried in the shade, are surveyed and described and the fruit's and seed's morphological characteristics. RESULT: The interspecific differences of morphological characteristics among the fruits and seeds are obvious. The characteristics are stable. A key for their identification is given. CONCLUSION: The above approach can be used as the taxonomic criteria for species differentiation.