Background & Objective: Radiotherapy and temozolomide are the standard therapy for newly diagnosed glioblastoma multiforme (GBM). However, it is unclear whether adding another agent to the commonly used radiotherapy-temozolomide (RT + TMZ) benefits newly diagnosed GBM patients. The present network meta-analysis aimed to assess the efficacy of combining other agents with RT + TMZ for GBM treatment. Methods: A comprehensive literature search was conducted on PubMed, EMBASE.com, Web of Science, and the Cochrane Central Register of Controlled Trials from inception to September 23, 2014, to include all randomized controlled trials of RT + TMZ-based therapy in GBM patients. Pairwise and network meta-analyses were performed to compare the therapeutic regimens. Results: Seventeen studies involving 4,148 patients were identified. The results of pairwise meta-analysis indicated no significant differences among most comparison groups, except for bevacizumab + RT + TMZ versus RT + TMZ for progression-free survival (hazard ratio [HR] = 0.71, 95% confidence interval [CI]: 0.59–0.86; P = 0.000) and RT + TMZ versus RT alone for overall survival (HR = 0.71, 95% CI: 0.58–0.88; P = 0.001). The results of network meta-analysis also showed no significant differences in most comparisons; however, adverse events were more common among patients receiving additional therapeutic agents other than RT + TMZ. The ranking probability analysis indicated that bevacizumab + RT + TMZ and nimustine + cisplatin + RT + TMZ were associated with the best progression-free and overall survival, but they also caused the most adverse events in GBM patients. RT + bevacizumab + irinotecan had the highest probability of being the best regimen for minimizing adverse events. Conclusions: The addition of other targeted agents, particularly bevacizumab and nimustine, to RT + TMZ could be slightly effective for the treatment of newly diagnosed GBM patients; however, adverse events remained common.
Glioblastoma

BACKGROUNDQuantitative T2 mapping has been a widely used method for the evaluation of pathological cartilage properties, and the histological assessment system of osteoarthritis in the rabbit has been published recently. The aim of the study was to investigate the effectiveness of quantitative T2 mapping evaluation for articular cartilage lesions of a rabbit model of anterior cruciate ligament transection (ACLT) osteoarthritis.

METHODSTwenty New Zealand White (NZW) rabbits were divided into ACLT surgical group and sham operated group equally. The anterior cruciate ligaments of the rabbits in ACLT group were transected, while the joints were closed intactly in sham operated group. Magnetic resonance (MR) examinations were performed on 3.0T MR unit at week 0, week 6, and week 12. T2 values were computed on GE ADW4.3 workstation. All rabbits were killed at week 13, and left knees were stained with Haematoxylin and Eosin. Semiquantitative histological grading was obtained according to the osteoarthritis cartilage histopathology assessment system. Computerized image analysis was performed to quantitate the immunostained collagen type II.

RESULTSThe average MR T2 value of whole left knee cartilage in ACLT surgical group ((29.05±12.01) ms) was significantly higher than that in sham operated group ((24.52±7.97) ms) (P=0.024) at week 6. The average T2 value increased to (32.18±12.79) ms in ACLT group at week 12, but remained near the baseline level ((27.66±8.08) ms) in the sham operated group (P=0.03). The cartilage lesion level of left knee in ACLT group was significantly increased at week 6 (P=0.005) and week 12 (P<0.001). T2 values had positive correlation with histological grading scores, but inverse correlation with optical densities (OD) of type II collagen.

CONCLUSIONThis study demonstrated the reliability and practicability of quantitative T2 mapping for the cartilage injury of rabbit ACLT osteoarthritis model.

Animals ; Anterior Cruciate Ligament ; metabolism ; physiopathology ; Cartilage, Articular ; metabolism ; physiopathology ; Collagen Type II ; metabolism ; Magnetic Resonance Imaging ; Male ; Osteoarthritis ; metabolism ; physiopathology ; Rabbits

Objective To study the pharmacokinetic features of reactive sulfide in rats after oral administration of Cinnabaris. Methods An HPLC coupled with precolumn derivatization method was developed for the pharmacokinetic features study on reactive sulfide in rats after oral administration of Cinnabaris. Results Good linearity (r>0.99) was found for reactive sulfide in plasma in the concentration range of 0.25–15 μmol/L (r>0.99). The LOQ and LOD of the method were 0.1 μmol/L and 0.02 μmol/L, respectively. The intra- and inter-day precision was less than 4.4% and 3.5% respectively, and the accuracy was -9.9%–6.0%. The average recovery rate was 74.9%. 0.6 g/kg Cinnabaris was given the rats for gavage, and the time-course pharmacokinetics parameters were as follows:Cmax(1.33±0.13) μmol/L, tmax(150±34) min, t1/2(323±62) min, AUC0-∞ (5743±297) ng/mL?h. Conclusion A sensitive, robust and accurate precolumn derivatization-HPLC method for the determination of plasma reactive sulfide is developed and validated. The method is successfully applied in the pharmacokinetic features study on reactive sulfide in plasma of rats after administration of Cinnabaris.

Objective To investigate the relationship between impaired glucose tolerance(IGT)and carotid atheromatous plague in patients with acute cerebral infarction and analyze the risk factors for plaque formation.Methods The 326 patients hospitalized in our department for acute cerebral infarction were divided into diabetes mellitus(DM)group,IGT group and normal glucose tolerance (NGT)group.The clinical features,biochemical indices and results of Doppler ultrasound examination of the carotid artery were compared between the 3 groups.Results The body mass index(BMI),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)of IGT group were markedly higher than those in NGT group(P＜0.05).Both the IGT and DM group showed significantly increased carotid intimal-medial thickness,plaque detection rate and the incidence of carotid scleratheroma in comparison with the NGT group(P＜0.05).Logistic regressive analysis identified age,TC,LDL-C and 2-h postprandial serum glucose as the independent risk factors for carotid scleratheroma.Conclusion In patients with acute cerebral infarction,those having impaired glucose often show obvious carotid scleratheroma with a severity similar to that in the DM patients.

Background::Mounting evidence, consistent with our previous study, showed that γ-aminobutyric acid type A receptor (GABAAR) played an indispensable role in airway inflammation and mucus hypersecretion in asthma. Monocyte chemotactic protein-inducing protein 1 (MCPIP1) was a key negative regulator of inflammation. Recent studies showed that inflammation was largely suppressed by enhanced MCPIP1 expression in many inflammatory diseases. However, the role and potential mechanism of MCPIP1 in airway inflammation and mucus hypersecretion in asthma were still not well studied. This study was to explore the role of MCPIP1 in asthmatic airway inflammation and mucus hypersecretion in both mice and BEAS-2B cells, and its potential mechanism.Methods::In vivo, mice were sensitized and challenged by ovalbumin (OVA) to induce asthma. Airway inflammation and mucus secretion were analyzed. In vitro, BEAS-2B cells were chosen. Interleukin (IL)-13 was used to stimulate inflammation and mucus hypersecretion in cells. MCPIP1 Lentiviral vector (LA-MCPIP1) and plasmid-MCPIP1 were used to up-regulate MCPIP1 in lung and cells, respectively. MCP-1, thymic stromal lymphopoietin (TSLP), mucin 5AC (MUC5AC), MCPIP1, and GABAARβ2 expressions were measured in both lung and BEAS-2B cells. Immunofluorescence staining was performed to observe the expression of GABAARβ2 in cells. Results::MCPIP1 was up-regulated by LA-MCPIP1 ( P < 0.001) and plasmid-MCPIP1 ( P < 0.001) in lung and cells, respectively. OVA-induced airway inflammation and mucus hypersecretion, OVA-enhanced MCP-1, TSLP, MUC5AC, and GABAARβ2 expressions, and OVA-reduced MCPIP1 were significantly blunted by LA-MCPIP1 in mice (all P < 0.001). IL-13-enhanced MCP-1, TSLP, MUC5AC, and GABAARβ2 expressions, and IL-13-reduced MCPIP1 were markedly abrogated by plasmid-MCPIP1 in BEAS-2B cells (all P < 0.001). Conclusion::The results of this study suggested that OVA and IL-13-induced airway inflammation and mucus hypersecretion were negatively regulated by MCPIP1 in both lung and BEAS-2B cells, involving GABAAR signaling pathway.

OBJECTIVEDiscussing the natural history and the influencing factors of HIV infection among former commercial blood and plasma donors engaged in unsafe blood donation practices in China.

METHODSUsing ambispective cohort study, with data obtained from ten counties (districts) from six provinces in the National AIDS Control Demonstration Area. HIV/AIDS cases were found and confirmed prior to July 24, 2006 being former commercial blood. Plasma donors were selected and data regarding infection, incidence, death, and influencing factors was collected. Analysis was performed using SPSS 12.0 statistical analysis software.

RESULTS(1) In 7551 cases of HIV infection, there were 6533 typical progressors (86.52%, 4757 cases of AIDS), 108 rapid progressors (1.43%), 910 long-term non-progressors (12.05%) with 4865 cases progressed to AIDS (64.43%). The median incubation period for HIV progression to AIDS was nine years (95% CI:8.96-9.04). (2) According to data, from a total of 1157 AIDS cases without ARV therapy (23.78% of total AIDS cases), there were 283 confirmed AIDS-related deaths, of which the median survival time was 6 months (95% CI:4-7) and the two and three year fatality rates were 95% and 99%, respectively. (3) The duration of HIV incubation period was irrespective to gender and age at the time of HIV infection (P > 0.05). Length of survival for untreated AIDS showed correlation to gender (P < 0.05) but no correlation with culture, marital status or age at the time of diagnosis of AIDS (P > 0.05).

CONCLUSIONCompared with the UNAIDS theory regarding slow disease progressors among adults, our study showed a longer AIDS incubation period and shorter outlook for untreated survival, but a similar incubation period for other routes of HIV infection.

Acquired Immunodeficiency Syndrome ; epidemiology ; mortality ; Adolescent ; Adult ; Aged ; Blood Donors ; statistics & numerical data ; China ; Female ; HIV Infections ; epidemiology ; mortality ; Humans ; Infectious Disease Incubation Period ; Male ; Middle Aged ; Young Adult

Antihypertensive Agents ; therapeutic use ; Blood Pressure ; physiology ; China ; Consensus ; Humans ; Hypertension ; diagnosis ; drug therapy ; epidemiology

Objective:To determine the contents of inorganic arsenic（iAs），monomethylarsonic acid（MMA） and dimethylarsinic acid（DMA） in brain tissues and blood by using hydride generation-cold trap-atomic absorptionspectrometry（HG-CT-AAS）， and to explore the toxic effects of Realgar on central nervous system of rats. Method:The 96 Wistar rats were randomly divided into 4 groups：normal control group，0.3，0.9 and 2.7 g·kg^-1 Realgar groups. They then received intragastric administration for 14，28 and 42 days respectively， so a total of 12 groups were formed， with 8 animals in each group. The normal group was given the same dose of sodium carboxymethyl cellulose （CMC-Na） by gavage. The contents of iAs，MMA and DMA in blood and brain tissues were determined by HG-CT-AAS. The novel object recognition test was conducted to observe the learning and memory ability of rats. The changes of hippocampal neuron ultrastructure were observed by transmission electron microscopy. Result:There was no difference in the growth，weight and hippocampal coefficient of the experimental animals. The method of HG-CT-AAS showed a good linearity，precision，accuracy and recovery in content determination of arsenic （at various forms） in rat brain and blood. MMA and DMA were detected in the brain of realgar groups at time-dose-effect relationship. iAs，MMA and DMA were detected in the blood of Realgar groups. The nuclear membrane， mitochondria and endoplasmic reticulum in hippocampus neurons of rats were gradually damaged with the increase of Rhubarb exposure dose and time. After 14 days of exposure to Realgar，compared with the normal control group，there was no significant difference in the novel object recognition index among Realgar groups. After 28 days of exposure，only 2.7 g·kg^-1 Realgar group showed statistically significant difference with the control group （P<0.05）. After 42 days of exposure， the novel object recognition index of 0.9 and 2.7 g·kg^-1 Realgar groups was significantly lower than that in normal control group（P<0.05）. Conclusion:The metabolites of Realgar in rats are iAs，MMA and DMA. MMA and DMA can be accumulated in the brain tissue through the blood-brain barrier，causing the decline of the ability of learning and memory and leading to damage of hippocampal neurons.