BACKGROUND:Autologous platelet rich plasma and bone marrow mesenchymal stem cells have certain effects on bone repair,but there are rare reports on the clinical treatment of long shaft fracture bone nonunion using autologous platelet rich plasma combined with bone marrow mesenchymal stem cell transplantation.OBJECTIVE:To investigate the therapeutic effect of autologous platelet rich plasma combined with bone marrow mesenchymal stem cell transplantation on long shaft fracture bone nonunion.METHODS:Forty-seven patients with long shaft fracture bone nonunion were randomly divided into two groups:monotherapy group (n=22) and combination group (n=25).In the monotherapy group,autologous bone marrow mesenchymal stem cell transplantation was performed in the bone nonunion site.In the combination group,autologous platelet rich plasma combined with bone marrow mesenchymal stem cell transplantation was implemented in the bone nonunion site.Callus score,clinical healing time,local complications and limb function grade were recorded and compared between the two groups.RESULTS AND CONCLUSION:The healing properties and limb function in the combination group were significantly superior to those in the monotherapy group [healing time:(4.2±1.5) vs.(5.6±1.1) months,P ＜ 0.05;healing rate:92％ vs.86％,P ＜ 0.05;callus score:2.74±0.36 vs.2.32±0.53,P ＜ 0.05;limb function recovery rate:77％ vs.84％,P ＜ 0.05].Complications like local skin redness or infection were not found in the two groups.In conclusion,both of the two methods can promote bone healing,but autologous platelet rich plasma combined with bone marrow mesenchymal stem cell transplantation has a better clinical effect on bone healing.

This paper was designed to observe the colocalization of 11beta-HSD1 and GR, and its significance in the rat hippocampus. Immunocytochemical dual-staining showed that not only 11beta-HSD1 but also GR immunoreactive substances were present in the cultured rat hippocampal neurons. Moreover, they were colocalized in the same hippocampal neuron. Synthetic glucocorticoid dexamethasone (DEX) up-regulated the protein expression and activity of 11beta-HSD1 in the cultured hippocampal neurons, as determined by Western blot and thin layer chromatography (TLC) respectively. The transfection of PC12 cells with the plasmid containing promoter sequence of 11beta-HSD1 gene and the reporter gene of CAT enzyme was conducted. DEX up-regulated the reporter gene expression in the system described above. The up-regulation of 11beta-HSD1 and reporter gene expression induced by DEX were both blocked by GR antagonist RU38486. Our study suggests that the colocalization of 11beta-HSD1 and GR in the hippocampus may be implicated in the up-regulation of 11beta-HSD1 expression by glucocorticoids combining to its promoter region, which in turn produces more biologically active glucocorticoids necessary for the binding of low affinity of GR.
11-beta-Hydroxysteroid Dehydrogenases ; genetics ; metabolism ; Animals ; Animals, Newborn ; Dexamethasone ; pharmacology ; Gene Expression Regulation ; Hippocampus ; cytology ; metabolism ; Mifepristone ; pharmacology ; Neurons ; chemistry ; metabolism ; PC12 Cells ; Promoter Regions, Genetic ; Rats ; Receptors, Glucocorticoid ; genetics ; metabolism ; Transfection

AIMTo prepare heart-protecting musk pH-dependent gradient-release pellets and investigate the drug release in vitro and in vivo.

METHODSThe pH-dependent gradient-release pellet system was prepared by using HPMC, Eudragit L-30D-55 and Eudragit L100-Eudragit S100 (1:5) combinations as coater. The release of borneol and total ginsenoside from pH-dependent gradient-release pellets were determined according to the method of Pharmacopoeia of the People's Republic of China (2000) in the simulated gastrointestinal pH conditions. The gastrointestinal transit and disintegration of pellets was investigated by using gamma-scintigraphic trace in volunteers. The pharmacokinetics of borneol of heart-protecting musk pH-dependent gradient-release pellets was studied in 6 healthy volunteers by GC methods.

RESULTSThe f2 value of release data of borneol and total ginsenoside of the heart-protecting musk pH-dependent gradient-release pellets was 79.6 in the simulated gastrointestinal pH conditions. The gamma-scintigraphic trace evaluation demonstrated that the pellets coated with HPMC, Eudragit L-30D-55 or Eudragit L100-Eudragit S100 (1:5) combinations can disintegrate in stomach, duodenum and jejunum or ileum. The gastrointestinal transit time of pellets was about 5 hours in fasted state and about 6 hours in fed state. The concentration-time curves of borneol of heart-protecting musk pills fit in two-compartment model. The pharmacokinetics data showed that borneol had a short time of absorption and elimination. The mean residence time (MRT) of borneol of heart-protecting musk pills was 2.61 hours. The plasma concentration of borneol of heart-protecting musk sustained-release capsule which consisted of three kinds of pellets coated with HPMC, Eudragit L-30D-55 or Eudragit L100-Eudragit S100 (1:5) combinations was steadier than those of heart-protecting musk pills, its Cmax was lower than and Tmax was near to those of heart-protecting musk pills, its MRT was 4.0 hours, and its relative bioavailability was 96%.

CONCLUSIONThe lipidsoluble borneol and watersoluble total ginsenoside of heart-protecting musk pH-dependent gradient-release pellets can release simultaneously while sustained-releasing in vitro. The heart-protecting musk pH-dependent gradient-release pellets had the characteristics of pH-dependent gradient-releasing and disintegration while transiting in gastrointestinal tract. A characteristic of gradient sustained-release was shown in the concentration-time curves of borneol of heart-protecting musk sustained-release capsule in volunteers.

Adult ; Bornanes ; pharmacokinetics ; Delayed-Action Preparations ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Fatty Acids, Monounsaturated ; administration & dosage ; Gastrointestinal Transit ; Ginsenosides ; pharmacokinetics ; Humans ; Hydrogen-Ion Concentration ; Lactose ; analogs & derivatives ; Male ; Materia Medica ; administration & dosage ; pharmacokinetics ; Methylcellulose ; analogs & derivatives ; Oxazines ; Polymethacrylic Acids ; Random Allocation

OBJECTIVETo investigate the effects of surgical treatment and prognosis of aneurysmal bone cyst (ABC) in mobile spine.

METHODSA total of 12 patients with ABC were operated on from 1996 to 2006, and the clinical data were retrospectively reviewed. The patients included 7 male and 5 female, aged from 16 to 52 years (mean, 29 years). Surgical interventions were selected according to WBB criteria. Seven patients underwent total spondylectomy, four underwent resection of posterior arch, one patient received sagittal resection only. Anti-poster or post-lateral approach reconstruction with bone-graft or bone cement and transpedicular screws fixation were performed in the cases. Eight cases received radiotherapy after the operation.

RESULTSThe mean operation blood lose was 3210 ml. The patients were followed-up for 10 to 116 months (mean, 41.8 months). Seven patients got complete recover of spinal cord function, 4 patients experienced local recurrence in 1-2 years post operation. One patient died of multiple metastasis of chondrosarcoma after radiotherapy.

CONCLUSIONSABC in spine is an aggressive disease with high local recurrence rate. Enbloc if possible provides the best result, with excellent prognosis. Radiotherapy should be selected carefully.

Adolescent ; Adult ; Bone Cysts, Aneurysmal ; diagnostic imaging ; surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Prognosis ; Radiography ; Retrospective Studies ; Spinal Diseases ; diagnostic imaging ; surgery ; Treatment Outcome

OBJECTIVETo evaluate the efficacy and safety of zoledronic acid in the treatment of bone pain in patients with bone metastasis from solid tumor or multiple myeloma.

METHODSA randomized, double-blind, double-simulated and multi-center phase III clinical trail with pamidronate as control was conducted. Patients with moderate to severe bone pain (VAS > 50 mm) induced by solid tumor or multiple myeloma were randomized to receive intravenous zoledronic acid 4 mg or pamidronate 90 mg. Then the change of VAS and urinary NTX/Cr and CTX/Cr were observed in two groups.

RESULTSFrom July 2005 to September 2006, 228 patients with bone pain induced by bone metastasis from 15 cancer centers were randomize into two groups: 116 patients in zoledronic acid group and 112 patients in pamidronate group. The VAS value was decreased gradually after treatment in these two groups. Significant improvement in bone pain after treatment were observed both in zoledronic acid group and the control group when compared with baseline VAS on D8 (-11.77% vs. -10.87%), D15 (-24.60% vs. -21.06%) and D28 (-32.37% vs. -31.26%) (P< or =0.0001), but no significant difference existed between two groups (P =0.6587). Compared with baseline, urine NTX/Cr and CTX/Cr level were decreased rapidly after treatment in both groups, the nadir was on D8, the median decreased on D28, which was -36.9% vs. -32.1% for NTX/Cr (P = 0.7922) and -63.2% vs. -47.9% for CTX/Cr (P =0.834). The frequently observed adverse events were pyrexia (19.0% vs. 31.3%), vomiting (6.0% vs. 8.9%), nausea (4.3% vs. 4.5%), fatigue (3.4% vs. 2.7%) and constipation (2.6% vs. 1.8%) in the two groups. Compared with baseline, the serum creatinine level was not significantly increased throughout the study.

CONCLUSIONIntravenous injection of 4 mg zoledronic acid can significantly reduce bone pain and bone resorption marker in urine in the Chinese patients with bone metastasis from solid tumor or multiple myeloma, which is tolerable and also comparable to pamidronate in the efficacy and safety.

Adult ; Aged ; Analgesics ; adverse effects ; therapeutic use ; Bone Density Conservation Agents ; adverse effects ; therapeutic use ; Bone Neoplasms ; complications ; secondary ; Breast Neoplasms ; pathology ; Collagen Type I ; urine ; Colorectal Neoplasms ; pathology ; Creatinine ; urine ; Diphosphonates ; adverse effects ; therapeutic use ; Double-Blind Method ; Female ; Fever ; chemically induced ; Humans ; Imidazoles ; adverse effects ; therapeutic use ; Lung Neoplasms ; pathology ; Male ; Middle Aged ; Multiple Myeloma ; complications ; Pain Measurement ; Pain, Intractable ; drug therapy ; etiology ; urine ; Peptides ; urine ; Prospective Studies ; Vomiting ; chemically induced

OBJECTIVE: Increased carotid artery intima-media thickness (CIMT) and carotid plaque as manifestations of carotid atherosclerosis have been used as markers of cardiovascular disease (CVD). The components of metabolic syndrome (MetS) are linked to CVD, but the association between MetS and CVD is controversial. METHODS: A total of 8,933 Chinese adults aged 40 years or older from 2010 to 2014 were selected from the Jidong and Kailuan communities. MetS was defined by the International Diabetes Federation criteria. CIMT and carotid plaque were measured using color Doppler ultrasound. Logistic regression models were used to assess the association of MetS with carotid plaque and CIMT. RESULTS: MetS was found among 3,461 (3,461/8,933) participants. The odds ratio and 95% confidence internal (CI) for carotid plaques in participants with MetS was 1.16 (1.03-1.30). The risk of carotid plaques increased with the number of MetS components. The average CIMT was higher in participants with MetS (β = 0.020, 95% CI, 0.014-0.027) and in participants with more MetS components. CONCLUSION Individuals with MetS are at an increased risk for carotid atherosclerosis compared to those without MetS.

OBJECTIVETo investigate the hemostatic effect of spleen-invigorating, qi-replenishing and blood-containing formula on simvastatin-induced zebrafish hemorrhage model, and to compare with the effect of clearing heat and cooling blood formula.

METHODSZebrafishes from breed A B line were treated with 0.5 µmol/L simvastatin for 24 hours to establish zebrafishes hemorrhage model. Under strict blinded experimental conditions, the above mentioned zebrafishes were then treated with experimental drug of different concentrations at the maximum non-lethal dose. The intervention effect of spleen-invigorating, qi-replenishing and blood-containing formula was comprehensively assessed by examining the main observational parameters, such as bleeding reduction rate and hemostasis rate while referring to additional parameters, such as blood flow, improvement rate of blood flow, velocity of movement, improvement rate of motion, which are characteristics of spleen qi deficiency.

RESULTSWhen the hemostatic effect of experimental drug B1 at the concentrations of 500 and 1 000 µg/ml, zebrafish bleeding rates were 30% and 15%, the hemostatic rate was 60% and 80%, respectively; when the experimental drug B2 at concentration of 500 and 1 000 µg/ml, Zebrafish bleeding rates were 45% and 40%, the hemostatic rate was 40% and 47%, respectively, showing that experimental drug B1 was superior to B2 in terms of decreasing bleeding rate and improving hemostatic effect in zebrafish. In the equal concentration, the experimental drug B1 was superior to B2 in terms of increasing and improving the blood flow of hemorrhagic zebrafish. Promotion and improvement of motion: in equal concentration, experimental drug B1 was superior to B2 in terms of promoting the motion velocity and increasing the improving rate of motion in zebrafish.

CONCLUSIONThe spleen-invigorating, qi-replenishing and blood-containing formula displays a good hemostatic effect on simvastatin-induced hemorrhage of zebrafish. It also boosts the blood flow and motion velocity in hemorrhagic zebrafish, therefore, providing an experimental basis for the treatment of syndrome of spleen failing to control blood by spleen-invigorating, qi-replenishing and blood-containing formula.

BackgroundNanotechnology is emerging as a promising tool to perform noninvasive therapy and optical imaging. However, nanomedicine may pose a potential risk of toxicity during in vivo applications. In this study, we aimed to investigate the potential toxicity of rare-earth nanoparticles (RENPs) using mice as models.

MethodsWe synthesized RENPs through a typical co-precipitation method. Institute of Cancer Research (ICR) mice were randomly divided into seven groups including a control group and six experimental groups (10 mice per group). ICR mice were intravenously injected with bare RENPs at a daily dose of 0, 0.5, 1.0, and 1.5 mg/kg for 7 days. To evaluate the toxicity of these nanoparticles in mice, magnetic resonance imaging (MRI) was performed to assess their uptake in mice. In addition, hematological and biochemical analyses were conducted to evaluate any impairment in the organ functions of ICR mice. The analysis of variance (ANOVA) followed by a one-way ANOVA test was used in this study. A repeated measures' analysis was used to determine any significant differences in white blood cell (WBC), alanine aminotransferase (ALT), and creatinine (CREA) levels at different evaluation times in each group.

ResultsWe demonstrated the successful synthesis of two different sizes (10 nm and 100 nm) of RENPs. Their physical properties were characterized by transmission electron microscopy and a 980 nm laser diode. Results of MRI study revealed the distribution and circulation of the RENPs in the liver. In addition, the hematological analysis found an increase of WBCs to (8.69 ± 0.85) × 10/L at the 28 day, which is indicative of inflammation in the mouse treated with 1.5 mg/kg NaYbF:Er nanoparticles. Furthermore, the biochemical analysis indicated increased levels of ALT ([64.20 ± 15.50] U/L) and CREA ([27.80 ± 3.56] μmol/L) at the 28 day, particularly those injected with 1.5 mg/kg NaYbF:Er nanoparticles. These results suggested the physiological and pathological damage caused by these nanoparticles to the organs and tissues of mice, especially to liver and kidney.

ConclusionThe use of bare RENPs may cause possible hepatotoxicity and nephritictoxicity in mice.

BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.

METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.

RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).

CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications

BACKGROUNDHepatitis B is an immune response-mediated disease. The aim of this study was to explore the differences of ratios of T-helper (Th) 2 cells to Th1 cells and cytokine levels in acute hepatitis B (AHB) patients and chronic hepatitis B virus (HBV)-infected patients in immune-tolerance and immune-active phases.

METHODSThirty chronic HBV-infected patients in the immune-tolerant phase (IT group) and 50 chronic hepatitis B patients in the immune-active (clearance) phase (IC group), 32 AHB patients (AHB group), and 13 healthy individuals (HI group) were enrolled in the study. Th cell proportions in peripheral blood, cytokine levels in plasma, and serum levels of HBV DNA, hepatitis B surface antigen, and hepatitis B e antigen were detected.

RESULTSThe Th1 cell percentage and Th2/Th1 ratio in the HBV infection group (including IT, IC, and AHB groups) were significantly different from those in HI group (24.10% ± 8.66% and 1.72 ± 0.61 vs. 15.16% ± 4.34% and 2.40 ± 0.74, respectively; all P < 0.001). However, there were no differences in the Th1 cell percentages and Th2/Th1 ratios among the IT, IC, and AHB groups. In HBV infection group, the median levels of Flt3 ligand (Flt3L), interferon (IFN)-γ, and interleukin (IL)-17A were significantly lower than those in HI group (29.26 pg/ml, 33.72 pg/ml, and 12.27 pg/ml vs. 108.54 pg/ml, 66.48 pg/ml, and 35.96 pg/ml, respectively; all P < 0.05). IFN-α2, IL-10, and transforming growth factor (TGF)-β2 median levels in hepatitis group (including patients in AHB and IC groups) were significantly higher than those in IT group (40.14 pg/ml, 13.58 pg/ml, and 557.41 pg/ml vs. 16.74 pg/ml, 6.80 pg/ml, and 419.01 pg/ml, respectively; all P < 0.05), while patients in hepatitis group had significant lower Flt3L level than IT patients (30.77 vs. 59.96 pg/ml, P = 0.021). Compared with IC group, patients in AHB group had significant higher median levels of IL-10, TGF-β1, and TGF-β2 (22.77 pg/ml, 10,447.00 pg/ml, and 782.28 pg/ml vs. 8.66 pg/ml, 3755.50 pg/ml, and 482.87 pg/ml, respectively; all P < 0.05).

CONCLUSIONSCompared with chronic HBV-infected patients in immune-tolerance phase, chronic HBV-infected patients in immune-active phase and AHB patients had similar Th2/Th1 ratios, significantly higher levels of IFN-α2, IL-10, and TGF-β. AHB patients had significantly higher IL-10 and TGF-β levels than chronic HBV-infected patients in immune-active phase.