Objective To investigate the expression of the interleukin-1 receptor(IL-1R)Ⅰ,IL-1RⅡand IL-1R accessory protein(IL-1RAcP)in osteoarthritis and analyse their biological significance.Methods Immunohistochemistry and reverse transcription-polymerase chain raction(RT-PCR)were adopted to detect the expression of IL-1RⅠ,IL-1RⅡand IL-1RAcP on the synovium of 107 OA patients.Results Immunohis- tochemistry showed strong positive expression of IL-1RⅠand IL-1RAcP,and positive expression of IL-1RⅡ. The expression was distributed in lining cells,monocyts and vascular endothelial cells of the sublining area, but all of them were negative or weak positive in normal synoviums.RT-PCR showed the expression of IL-1RⅠ,IL-1RⅡand IL-1RAcP in OA synoviums was significantly enhanced than normal synoviums (P＜0.05),and the expression of IL-1RⅠwas significantly enhanced than IL-1RⅡ(P＜0.05),but no sig- nificant difference with IL-1RAcP(P＞0.05).In stageⅡandⅢOA synoviums,the expression of IL-1RⅠand IL-1 RAcP had no significant difference with normal synoviums(P＞0.05).The expression of IL-1RⅡin stageⅢOA synoviums was significantly enhanced than normal(P＜0.05).Conclusion IL-1RⅠ,IL-1RⅡand IL-1RAcP play significant roles in the pathogenesis of OA,especially IL-1RⅠand IL-1RAcP.But their increase is only observed in the early stage of OA.These suggest that they may have no association with the development of OA and have no direct association with the severity of OA.OA can be cured by interrupting the signal transduction path in which IL-1 has played biological roles.

OBJECTIVEPosterolateral intertransverse process fusion was performed in aged and young adult female rabbits lumbar spine using recombinant human bone morphogenetic protein-2 (rhBMP-2) and autograft to reveal the function of rhBMP-2 on spinal fusion on aged animals.

METHODSA total of 24 female New Zealand white rabbits included 12 young adult of 6 months and 12 aged of 2-year-old, was divided into 4 groups: (1) young adult autologous iliac crest bone group [ICBG(Y), n=6); (2) young adult rhBMP-2/absorbable collagen sponge (ACS) group [BMP-2(Y), n=6]; (3) aged autologous iliac crest bone group [ICBG(O), n=6]; aged rhBMP-2/ACS group [BMP-2(O), n=6]. All were underwent posterolateral fusion in same day. rhBMP-2 and autologous iliac crest bone was implant bilateral LS-L6 intertransverse processes, respectively. Half of the rabbits were sacrificed at 3.6 weeks following surgery, respectively. The results were assessed by manual palpation, radiographs, computed tomographic scans (3D) and histology.

RESULTSSix weeks after surgery, radiography, computed tomography and histology indicated the different result in healing in the posterolateral fusion using rhBMP-2 compared to ICBG (P < 0.05). Aged BMP-2 group showed significantly higher fusion rates than Aged ICBG group.

CONCLUSIONThis study demonstrated rhBMP-2 can increase the posterolateral fusion rate and new bone quality in aged rabbitss than autograft, it may take the place of ICBG. But its role is effected by age.

Aging ; Animals ; Bone Morphogenetic Protein 2 ; pharmacology ; Female ; Humans ; Palpation ; Rabbits ; Recombinant Proteins ; pharmacology ; Spinal Cord ; drug effects ; pathology ; surgery ; transplantation ; Spinal Fusion ; Tomography, X-Ray Computed ; Transplantation, Autologous

OBJECTIVETo determine the mechanism underlying the therapeutic activities of glycogen synthase kinase 3b (GSK3b) against hepatic ischemia-reperfusion (H-IR) injury by investigating the inhibitive effects of GSK3b on inflammation mediated by Toll-like receptor 4 (TLR4).

METHODSC57BL/6 male mice were subjected to 90 min of warm liver cephalad lobe ischemia, followed by reperfusion for various lengths of time. The mice were divided into three groups: the H-IR untreated model (control group), and the H-IR inflammation-induced models that received an intraperitoneal injection of purified lipopolysaccharide (LPS) endotoxin alone (inflammation group) or with pretreatment of the SB216763 GSK3b-specific inhibitor (intervention group). To create a parallel isolated cell system for detailed investigations of macrophages, marrow-derived stem cells were isolated from femurs of the H-IR control group of mice and used to derive primary macrophages. The cells were then divided into the same three groups as the whole mouse system: control, LPS-induced inflammation model, and inflammation model with SB216763 intervention. Differential expressions of inflammation-related proteins and genes were detected by Western blotting and real-time quantitative PCR, respectively.

RESULTSThe phosphorylation levels of ERK, JNK and p38 MAPK were induced in liver at 1 h after reperfusion, but then steadily decreased and returned to baseline levels by 4 h after reperfusion. In addition, the phosphorylation levels of ERK and JNK were induced in macrophages at 15 min after LPS stimulation, while the phosphorylation level of p38 MAPK was induced at 1 h; SB216763 pretreatment suppressed the LPS-stimulated ERK, JNK and p38 phosphorylation in macrophages. In the mouse model, GSK3b activity was found to promote the gene expression of anti-inflammatory cytokine IL-10 (control: 0.21 ± 0.08, inflammation: 0.83 ± 0.21, intervention: 1.76 ± 0.67; F = 3.16, P = 0.027) but to significantly inhibit the gene expression of pro-inflammatory cytokines IL-12 (control: 0.11 ± 0.05, inflammation: 0.85 ± 0.11, intervention: 0.43 ± 0.10; F = 2.67, P = 0.038), TNF-a, (control: 0.052 ± 0.012, inflammation: 8.11 ± 0.98, intervention: 3.9 ± 0.82; F = 4.13, P = 0.016), IL-6 (control: 0.22 ± 0.08, inflammation: 6.37 ± 0.81, intervention: 2.11 ± 0.63; F = 3.21, P = 0.024), and IL-1b (control: 0.12 ± 0.07, inflammation: 2.51 ± 0.62, and intervention: 1.28 ± 0.33; F = 2.22, P = 0.030).

CONCLUSIONInhibition of GSK3b selectively regulates the expression of anti-inflammatory and pro-inflammatory cytokines in liver Kupffer cells (liver macrophages). This process may be one of the mechanisms underlying the ability of GSK3b to ameliorate hepatic ischemia-reperfusion injury, possibly because inhibition of pro-inflammatory cytokines may indirectly mediate liver cell apoptosis.

Animals ; Cells, Cultured ; Cytokines ; metabolism ; Glycogen Synthase Kinase 3 ; metabolism ; Glycogen Synthase Kinase 3 beta ; Inflammation ; metabolism ; pathology ; Lipopolysaccharides ; adverse effects ; Liver ; pathology ; Macrophages ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Reperfusion Injury ; Toll-Like Receptor 4 ; metabolism

BACKGROUNDTo study the anti-SARS virus activities of different recombinant human interferons on the cell culture system.

METHODSAnti-SARS virus activities of interferons were determined by using CPE inhibition test in human skeletal muscle sarcoma (Rda) cell culture.

RESULTSThe average minimum amount of interferon alpha 2b, alpha 1b, beta 1b or omega 1b to inhibit 50% CPE in Rda cell culture was (160.5+/-129.5) IU/ml, (149.0+/-71.7) IU/ml, (69.5+/-61.5) IU/ml, (87.3+/-47.1) IU/ml, respectively or (0.6+/-0.5) ng/ml, (10.6+/-5.1) ng/ml, (3.5+/-3.1) ng/ml, (0.9+/-0.5) ng/ml, respectively.

CONCLUSIONAll the tested recombinant interferons showed anti-SARS virus activities on the Rda cell culture with different sensitivities.

Antiviral Agents ; pharmacology ; Cell Line, Tumor ; Humans ; Interferon Type I ; pharmacology ; Interferon-alpha ; pharmacology ; Recombinant Proteins ; SARS Virus ; drug effects ; Severe Acute Respiratory Syndrome ; drug therapy ; virology

BACKGROUNDTherapeutic hypothermia has been recommended for the treatment of cardiac arrest patients who remain comatose after the return of spontaneous circulation. The aim of this study was to evaluate the effectiveness and safety of mild hypothermia on patients with cardiac arrest by conducting a meta-analysis.

METHODSThe relevant trials were searched in Cochrane Library, PubMed, Web of Science, Embase, CNKI and Wan Fang Data from the date of their establishment to October 2014. Thereafter, the studies retrieved were screened based on predefined inclusion and exclusion criteria. Data were extracted, and the quality of the included studies was evaluated. A meta-analysis was conducted using the Cochrane Collaboration Review Manager 5.2 software.

RESULTSSix randomized controlled trials involving 531 cases were included, among which 273 cases were assigned to the treatment group and the other 258 cases to the control group. The meta-analysis indicated that mild hypothermia therapy after cardiac arrest produced significant differences in survival rate (relative risk [RR] =1.23, 95% confidence interval [CI]: 1.02-1.48, P = 0.03) and neurological function (RR = 1.33, 95% CI: 1.08-1.65, P = 0.007) after 6 months compared with normothermia therapy. However, no significant differences were observed in the survival to the hospital discharge (RR = 1.35, 95% CI: 0.87-2.10, P = 0.18), favorable neurological outcome at hospital discharge (RR = 1.53, 95% CI: 0.95-2.45, P = 0.08) and adverse events.

CONCLUSIONSThe meta-analysis demonstrated that mild hypothermia can improve the survival rate and neurological function of patients with cardiac arrest after 6 months. On the other hand, regarding the survival to hospital discharge, favorable neurological outcome at hospital discharge, and adverse events, our meta-analysis produced nonsignificant results.

Cardiopulmonary Resuscitation ; Heart Arrest ; therapy ; Humans ; Hypothermia, Induced ; methods

Objective To investigate the molecular epideiological and clinical feature of human metapneumovirus in children with acute respiratory tract infection in Nanjing city, China. Method Nasopharyngeal aspirates and nasopharyngeal swab were taken from 642 outpatients or hospitalized pediatric patients with acute at the Children Hospital of Nanjing,Jiangsu Province, China, between August 2009 and July 2010. Respiratory speciments were tested for the M gene of hMPV by reverse-transcription polymerase chain reaction (RT-PCR). All RT-PCR positive products were sequenced and phlogenetic analysis was conducted. Result hMPV was detected in 35 (5.5%) of the 642 children. Phylogenetic analysis revealed that 51.4% of the hMPV were B1, 31.4% were A2b. The peak of the positive rate was in April. The majority of the hMPV-positive patients(71.4% ) were 0-1 years old. Of the 35 hMPV-positive patients, 15 (42. 8% ) were co-infected with other respiratory viruses, and human rhinovirus (HRV) were the most common additional respiratory virus. The most common clinical diagnosis was pneumonia (48. 6% ).Conclusion Human metapneumovirus is an important pathogen of acute respiratory tract infection in children in Nanjing city. The subtype B1 was the predominating lineage in 2009-2010 in Nanjing city. No significant differences were found for clinical characteristics between genotype A and genotype B human metapneumovirus infection in children in Nanjing.

OBJECTIVETo study the preventive effect of recombinant human interferon alpha-2b for nasal spray against SARS and other common respiratory viral infections by serum-epidemiological method.

METHODSA randomized, placebo-controlled, double-blind field trial study in populations with 14,391 persons from SARS prevalent cities or provinces in China during May-Jun, 2003 and Dec-Apr, 2004. Interferon alpha-2b was given twice per day, once 9 x 10(5) IU by nasal spray for 5 days. Serum samples were taken at 15 days after last administration. Serological tests included SARS IgG antibody and IgM antibodies against influenza B, parainfluenza virus types 1-3, adenovirus type 3, 7 and respiratory syncytial virus by using commercial ELISA kits.

RESULTSNo statistically significant difference in serum SARS IgG antibody positive rate was found between the interferon and control groups among 2,757 serum samples. On the other hand, after using interferon, all four respiratory viruses (parainfluenza virus types 1-3 influenza B, adenovirus types 3, 7 and respiratory syncytial virus) in interferon group had lower IgM antibody positive rates than those in control group. Among them there were statistically significant differences between the interferon and control groups for parainfluenza virus, influenza B and adenovirus. The preventive efficacy of interferon against four respiratory viruses was different, from high to low, the rank was Flu B (66.76%), parainfluenza types 1-3 (66.75%), RSV (39.61%) and adenovirus (32.86%). The average preventive efficacy was 50.27%.

CONCLUSIONThe recombinant human interferon alpha-2b for nasal spray could decrease the rates of common respiratory viruses infection in the selected population.

Administration, Intranasal ; Adult ; Antibodies, Viral ; blood ; Antiviral Agents ; administration & dosage ; therapeutic use ; Double-Blind Method ; Humans ; Immunoglobulin G ; blood ; Immunoglobulin M ; blood ; Interferon-alpha ; administration & dosage ; therapeutic use ; Recombinant Proteins ; Respiratory Tract Infections ; blood ; prevention & control ; virology ; SARS Virus ; drug effects ; immunology ; Severe Acute Respiratory Syndrome ; blood ; chemically induced ; prevention & control ; Treatment Outcome ; Young Adult

OBJECTIVETo explore the role of the mutation of presenilin-1 exon 6 in pathogenesis of Alzheimer's disease(AD) patients.

METHODSExon 6 of presenilin-1 was analyzed by use of polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA analyzer technique in 2 patients with familial AD, 53 patients with sporadic DA, 60 patients with vascular dementia(VD) and 90 normal controls.

RESULTSMobility shift of SSCP in exon 6 of presenilin-1 was detected in 2 cases with FAD, 4 cases with SDA and 1 case with VD. Two missense mutations were found in the patients by DNA sequence analysis, one mutation was 1123 nt C-->G(Cys 23 Trp) and the other was 1300 nt A-->C(Asp 200 Ala).

CONCLUSIONMutations in exon 6 of presenilin-1 existed in the patients with FAD and SDA, and the two missense mutations were probably pathological by nature.

Aged ; Aged, 80 and over ; Alzheimer Disease ; genetics ; Exons ; genetics ; Female ; Humans ; Male ; Mutation ; Mutation, Missense ; Pedigree ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational ; Presenilin-1 ; genetics ; Sequence Analysis, DNA

OBJECTIVETo explore the way to induce mesenchymal stem cells (MSCs) to differentiate into dopaminergic neurons in vitro.

METHODSMSCs were obtained from rat bone marrow, cultured and passaged. MSCs used in this experiment had multipotency, which was indirectly proved by being induced to differentiate into chondrocytes and adipocytes. MSCs were cultured in medium containing 0.5 mmol/L IBMX for 2 days. Then the medium was replaced with induction medium, which contained GDNF, IL-1beta, mesencephalic glial-cell-conditioned medium and flash-frozen mesencephalic membrane fragments. The surface markers of the differentiated neurons, such as NSE, nestin, MAP-2a, b and TH were detected by immunocytochemistry and Western blot after MSCs were cultured in induction medium for 7 days and 15 days.

RESULTSMSCs differentiated into neural progenitors and expressed nestin after MSCs were incubated with medium containing IBMX for 2 d. After the medium was replaced with induction medium containing many inducing agents, MSCs differentiated into neuron-like cells and dopaminergic neuron-like cells and expressed NSE, MAP-2a, b and TH. The percentage of NSE-positive cells, MAP-2a, b-positive cells and TH-positive cells was 30.032 +/- 2.489%, 41.580 +/- 5.101% and 34.958 +/- 5.534%, respectively after MSCs were induced in medium containing GDNF, IL-1beta, mesencephalic glial-cell-conditioned medium and flash-frozen mesencephalic membrane fragments for 15 days.

CONCLUSIONMSCs can differentiate into dopaminergic neuron-like cells and are a new cell source for the treatment of neurodegeneration diseases and have a great potential for wide application.

Adipocytes ; cytology ; Animals ; Blotting, Western ; Bone Marrow Cells ; Carboxylesterase ; analysis ; Cell Differentiation ; Cells, Cultured ; Chondrocytes ; cytology ; Culture Media, Conditioned ; Dopamine ; analysis ; Intermediate Filament Proteins ; analysis ; Mesencephalon ; cytology ; Mesenchymal Stromal Cells ; cytology ; Nerve Tissue Proteins ; analysis ; Nestin ; Neurons ; cytology ; metabolism ; Phosphoprotein Phosphatases ; analysis ; Rats ; Rats, Wistar

OBJECTIVESTo understand the epidemiological characteristics of severe acute respiratory syndrome (SARS) outbreaks in some areas of Guangdong province and to provide scientific basis for prevention and control measures against it.

METHODSStandardized questionnaire was used on individual cases. Data on the epidemiological characteristics as time, place, persons and aggregation status of SARS cases, development of the epidemics, were analyzed with software EPI 6.0.

RESULTSThe incidence of SARS in Guangdong province was 1.72/100,000 with case fatality rate as 3.64%. Most cases of SARS occurred between the last ten days of January and the first ten days of February with the peak (61.88% of the patients) occurred in the first ten days of February. As to the distribution of place, Pearl river delta region-economically developed with great number of mobile population-was heavily affected areas (account for 96.66% of the total patients). The majority of patients were young adults and medical staff seemed to be the most affected subgroup (account for 24.9% of the patients in total). Family and hospital aggregation of patients comprised the another two important characteristics of SARS (account for 37.1% of the total patients).

CONCLUSIONCurrent knowledge on SARS suggested that it was an air-borne infectious disease with human beings served as the source of infection. The incubation period of the disease was from 1 to 12 days with a median of 4 days. Respiratory secretions and close contact contributed to person-to-person transmission. Most cases were distributed in Pearl river delta region, an area famous for its economic development and heavy flow of mobile population.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; China ; epidemiology ; Contact Tracing ; Disease Outbreaks ; Family Health ; Female ; Humans ; Incidence ; Infectious Disease Transmission, Patient-to-Professional ; Male ; Middle Aged ; Retrospective Studies ; Severe Acute Respiratory Syndrome ; epidemiology ; mortality ; Surveys and Questionnaires