Objective To investigate the effect of intraperitoneal injection of thalidomide on pain behaviors in a mouse model of bone cancer pain. Methods 36 male C3H/HeJ mice were divided randomly into tumor group (n= 18) and sham group (n= 18) ,six mice from each group were chosen to examine the time course of changes in behavior after tumor cells inoculated to the bone. 2 × 105 osteosarcoma NCTC 2472 cells were implanted into the intramedullary space of the right femurs of mice to induce ongoing bone cancer related pain behaviors. The sham group was inoculated by α-MEM without any cells. On the day before inoculation,the tumor mice were divided randomly into tumor + thalidomide group and tumor + vehicle group. The sham group mice were further divided randomly into sham + thalidomide group and sham + vehicle group. Pain ethology indexes such as paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were observed on 1 d before inoculation and on 3 d ,5 d ,7 d, 10 d, 14 d after inoculation. Results ( 1 ) At day 7 after the operation, compared with sham mice ( 1. 70 ± 0. 33 ) g, PWMT of tumor mice decreased to ( 1.07 ± 0. 30) g (P ＜ 0. 05 ). At day 10, PWTL shortened to ( 12.60 ± 1.69 ) s (P ＜ 0. 05 ) compared with sham mice ( 17.70 ± 1.54 ) s. And the pain behaviors of tumor mice were aggravated along with the development of cancer pain. (2) At day 7 after the operation, compared with tumor + vehicle group ( 1. 07 ± 0.39 ) g, PWMT of tumor + thalidomide group increased to ( 1. 53 ± 0. 39 ) g (P ＜0.05). At day 10, PWTL extended to ( 16.48 ± 1.13 ) s compared with sham mice ( 12.64 ± 1. 56) s (P ＜0. 05 ). Conclusion Intraperitoneal injection of thalidomide can efficiently relieve mechanical hyperalgia and thermal hyperalgia in a mouse model of bone cancer pain.

Aim The relative bioavailability of domestic ibudilast sustained release capsules in healthy volunteers was observed.Methods A single oral dose of 20 mg of imported and domestic ibudilast sustained release capsules and 10 mg of ibudilast raw material was separately given to 12 healthy volunteers in a randomized crossover study. Ibudilast concentration in plasma was determined by HPLC method.Results The Cmax were (54.9?9.7),(60.7?9.1) and (62.2?11.5) ?g?L-1; the tmax were (3.8?0.8),(3.9?0.8) and (1.8?0.3) h;the t1/2(ke) were (1.5?1.4),(12.1?1.0) and (3.5?0.5) h,and the AUC(0～t) were (618.1?57.7),(588.1?66.6) and (233.0?46.4) ?g?h?L-1 in imported capsule group, domestic capsule group and raw material group respectively. The relative bioavailability of domestic sustained release capsules of ibudilast is (95.6?11.0)%. Conclusion The results of statistical analysis demonstrate that the imported and domestic sustained capsules have significant character of significantly sustained release and are bioequivalent.

Alkaloids ; pharmacology ; Animals ; Liver Neoplasms, Experimental ; enzymology ; prevention & control ; Quinolizines ; pharmacology ; Rats ; Selenium ; pharmacology ; Telomerase ; metabolism ; Yeast, Dried ; pharmacology

BACKGROUNDWe investigated the pathogenesis of atherosclerosis in diabetes, and detected the expression of scavenger receptor CD36 in monocytes in patients with type 2 diabetes.

METHODSAccording to the criteria by WHO, diabetic patients were classified into two groups: well controlled diabetic patients (WCP) and poorly controlled diabetic patients (PCP). The expression of CD36 protein and mRNA were evaluated by flow cytometry and reversal transcription polymerase chain reaction (RT-PCR). Plasma levels of accumulation of oxidized LDL (oxLDL) were directly measured by sandwich enzyme-linked immunosorbent assay (ELISA) method.

RESULTSFlow cytometry and RT-PCR showed that the mean fluorescence intensity (MFI) of CD36 in monocyte and CD36 mRNA were significantly higher in the PCP and WCP in comparison with healthy controls (P<0.01). CD36 MFI and mRNA in the PCP were increased by 78% and 36% compared to the WCP. In both groups, CD36 MFI and mRNA were significantly higher in patients with diabetic atherosclerosis in comparison with those without diabetic atherosclerosis (P<0.05). No significant difference was found in CD14 expression between the groups (P>0.05). The concentrations of plasma oxLDL were higher in the PCP group compared to WCP and control group (P<0.05), whereas oxLDL average values did not differ significantly between WCP and control groups (P>0.05). In the WCP and PCP groups, oxLDL levels were higher in patients with diabetic atherosclerosis than those without diabetic atherosclerosis (P<0.05).

CONCLUSIONSThe increased expression of scavenger receptor CD36 may be one of the mechanism of accelerated atherosclerosis in diabetic. The poorly controlled diabetes patients are at higher risk for the vascular complications than the well controlled diabetic patients.

Adult ; Aged ; Atherosclerosis ; etiology ; CD36 Antigens ; genetics ; Diabetes Mellitus, Type 2 ; complications ; Female ; Fluorescent Antibody Technique ; Humans ; Lipoproteins, LDL ; analysis ; Male ; Middle Aged ; Monocytes ; metabolism ; RNA, Messenger ; analysis ; Regression Analysis

China ; Clinical Trials as Topic ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Humans ; Kidney Diseases ; drug therapy ; Prospective Studies ; Retrospective Studies ; Tripterygium

OBJECTIVETo observe the correlation between brain-derived neurotrophic factor (BDNF) expression in the nerve system of diabetes mellitus (DM) rats and diabetic erectile dysfunction (ED).

METHODSDM rats were induced by injecting streptozotocin and erectile function test was done by injecting apomorphine (APO) at 1 month, 2 months, 3 months and 4 months. Then the brain, lumbosacral spinal cord, thoracic and lumbar sympathetic trunks, penis and prostate were taken from the diabetic and normal rats of the same age. The BDNF positive neurons and nerve fibers were shown by immunohistochemistry or fluorescence immunohistochemistry. The number and the grey density of BDNF positive cells and fibers were detected by image analysis.

RESULTSCompared with the control group, the erection frequency of the DM rats decreased at 2 months (P <0. 05) , and significantly at 3 and 4 months (P > 0.01) , and the BDNF positive neurons and nerve fibers in the cerebral cortex, lumbosacral spinal cord, thoracic and lumbar sympathetic trunks, penis and prostate of 1-month DM rats were reduced (P <0. 05). As time went on, BDNF declined progressively.

CONCLUSIONBDNF decreases in the central and peripheral nerve system in the early stage of diabetes mellitus, wich is closely correlated with diabetic ED.

Animals ; Brain-Derived Neurotrophic Factor ; biosynthesis ; Diabetes Mellitus, Experimental ; physiopathology ; Erectile Dysfunction ; physiopathology ; Male ; Nerve Tissue ; metabolism ; Rats ; Rats, Sprague-Dawley

In 2007, an outbreak of hand, foot, and mouth disease (HFMD) occurred in Jungar Banner, Erdos city, Inner Mongolia Autonomous Region, China Fever, vesicular exanthema on the hands, feet, mouth, and buttocks were presented in most of the patients. Most of the patients were infants less than 5 years old, and an obvious peak period appeared in the disease outbreak. From 28 hospitalized patients, 23 stool specimens and 6 throat swab specimens were collected for enterovirus isolation, and 15 enteroviruses were isolated, 9 were identified as Human Enterovirus 71 (HEV71, the isolation rate is 31.03%) and 1 was identified as Coxsackievirus A16 (CVA16). According to the comprehensive analysis of clinical manifestation, epidemiology data and laboratory results, this outbreak was probably mainly caused by HEV71. The variability at nucleotide acid level and amino acid level among 9 HEV71 was relatively low, and the homology was more than 99.4% and 99.0% respectively, showing that this outbreak was caused by only one viral transmission chain. Phylogenetic analysis of 9 HEV71 strains isolated during this outbreak revealed that they all belonged to subgenotype C4, which has been continuously circulating in mainland China since its first reported occurrence in Shenzhen City in 1998. It was also suggested that subgenotype C4 HEV71 had a widely distribution and transmission in mainland China.
China ; epidemiology ; Enterovirus ; physiology ; Enterovirus A, Human ; classification ; genetics ; physiology ; Hand, Foot and Mouth Disease ; epidemiology ; virology ; Humans ; Molecular Sequence Data ; Phylogeny ; Polymerase Chain Reaction ; Sequence Analysis, DNA

OBJECTIVETo determine the gene mutation spectrum of patients with 6-pyruvoyltetrahydrobiopterin synthesis deficiency (PTPSD) in Mainland China.

METHODSThe 6-pyruvoyltetrahydrobiopterin synthesis gene lz(PTS)lz was analyzed in 55 PTPSD patients by using PCR-restriction fragment length polymorphism (PCR-RFLP) and direct DNA sequencing. The relationship between the genotype and phenotype was analyzed.

RESULTSEighteen mutations were identified and the detection rate of gene mutation was 95.28%. Four hot-spot mutations, namely P87S (40.57%), N52S(13.21%), D96N(12.26%) and IVS1nt-291A to G(10.38%) were found in this study, and the first three were associated with severe phenotype. The P87L was reported firstly in Chinese patients, and the Q13X, M80T, IVS4nt-2A to G, L93M and K131N were novel mutations.

CONCLUSIONThe P87S, N52S, D96N and IVS1nt-291A to G mutations are the hot-spots mutations of the PTS gene in Chinese PTPSD patients. Using PCR-RFLP technique to screen the mutations in the PTS gene can increase the efficiency of gene diagnosis.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; DNA Mutational Analysis ; Female ; Genotype ; Humans ; Male ; Metabolic Diseases ; genetics ; Mutation ; Pedigree ; Phenylalanine Hydroxylase ; genetics ; metabolism ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Pregnancy ; Pterins ; metabolism ; Steroid 21-Hydroxylase ; genetics ; metabolism

OBJECTIVETo investigate the bacterial pathogenic characteristics of respiratory tract infection in children.

METHODSThe medical data from 14,994 children with respiratory tract infection who were hospitalized in Children's Hospital Affiliated to Soochow University between November 2005 and October 2014 were retrospectively reviewed.

RESULTSAmong the 14,994 sputum samples from the children with respiratory tract infection, 3,947 (26.32%) had a positive bacterial culture. The most common bacterial pathogen was Streptococcus pneumonia (12.79%), followed by Haemophilus influenzae (5.02%) and Moraxella catarrhalis (2.91%). The bacterial detection rates differed significantly in different years and seasons and children of different ages (P<0.01). The children who had not taken antibacterial agents before admission had a significantly higher positive bacterial culture rate than those who had taken antibacterial agents (P<0.01). There were significant differences in the bacterial detection rate among the children with different course of disease (<1 month, 1-3 months and >3 months) (P<0.05). The detection rates of Streptococcus pneumonia, Moraxella catarrhalis and Acinetobacter baumannii showed an increased trend with a prolonged disease course (P<0.05).

CONCLUSIONSStreptococcus pneumonia is the most common bacterial pathogen causing respiratory tract infection in children, followed by Haemophilus influenzae and Moraxella catarrhalis. The detection rate of bacterial pathogens varies in different years and seasons and children of different ages. The course of the disease and application of antibacterial agents outside hospital can affect the detection rate of bacterial pathogens in children with respiratory tract infection.

Adolescent ; Anti-Bacterial Agents ; therapeutic use ; Bacteria ; isolation & purification ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Respiratory Tract Infections ; microbiology ; Seasons ; Time Factors

OBJECTIVETo construct glypican-3 (GPC-3) short hairpin RNA (shRNA) and investigate the effects of GPC-3 transcription silencing on hepatoma cell invasion and angiogenesis mechanisms.

METHODSGPC-3-specific shRNA and non-target control shRNA were constructed and transfected into the human hepatoma cell lines HepG2, MHCC-97H, and Huh7. shRNA-mediated silencing of GPC-3 expression was confirmed at the mRNA and protein levels by fluorescence quantitative reverse transcription (FQRT)-PCR and western blotting, respectively. The effect of silenced GPC-3 expression on cell proliferation was detected by EdU and sulforhodamine B assays, on migration by wound healing (scratch) assay, on invasion by transwell chamber assay, and on apoptosis by luminescence assay of caspase-3/7 activity. The effect of silenced GPC-3 expression on angiogenesis-related signaling factors was detected by FQRT-PCR (for the glioma-associated oncogene homolog-1 hedgehog signaling factor, GLI1, and the beta-catenin Wnt signaling factor, b-catenin), immunofluorescent staining (for the insulin-like growth factor-II, IGF-II), and ELISA (for the vascular endothelial growth factor, VEGF). Pairwise comparisons were made by the independent sample t-test, and multiple comparisons were made by one-way ANOVA.

RESULTSIn all cell lines, transfection with the GPC-3-specific shRNA significantly reduced GPC-3 mRNA levels (% reduction as compared to the non-target control shRNA: HepG2, 89.2+/-6.0%, t = -25.753, P less than 0.001; MHCC-97H, 75.3+/-4.9%, t = -26.487, P less than 0.001; Huh7, 73.6+/-4.6%, t = -27.607, P less than 0.001); the GPC-3 protein levels were similarly reduced. The GPC-3 shRNA-silenced cells showed significantly reduced proliferative, migratory and invasive capacities, as well as significantly increased apoptosis. The shRNA-mediated GPC-3 silencing was accompanied by significant down-regulation of b-catenin mRNA (HepG2, 46.9+/-0.6%; MHCC-97H, 67.5+/-2.7%; Huh7, 56.3+/-8.4%) and significant up-regulation of GLI1 mRNA (HepG2, 49.2+/-28.6%; MHCC-97H, 54.6+/-24.4%; Huh7, 31.6+/-15.7%). At 72 h after transfection, the HepG2 cells showed significant down-regulation of VEGF protein (54.3+/-1.5%, t = 46.746, P less than 0.001).

CONCLUSIONGPC-3 contributes to migration, invasion, angiogenesis, and apoptosis of hepatoma cells, possibly through its interactions with the Wnt/b-catenin and Hedgehog signaling pathways. GPC-3 may represent a useful target for gene silencing by molecular-based therapies to treat hepatocellular carcinoma.

Apoptosis ; Carcinoma, Hepatocellular ; blood supply ; metabolism ; pathology ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Gene Silencing ; Glypicans ; genetics ; Humans ; Liver Neoplasms ; blood supply ; metabolism ; pathology ; Neoplasm Invasiveness ; Neovascularization, Pathologic ; RNA, Messenger ; genetics ; metabolism ; RNA, Small Interfering ; genetics ; Signal Transduction ; Transfection ; Vascular Endothelial Growth Factor A ; metabolism ; beta Catenin ; metabolism