OBJECTIVETo investigate the role of lung resistance-related protein (LRP) in intrinsic multidrug resistance (MDR) of bladder cancer and detect the relationship of LRP expression with the clinical pathologic parameters.

METHODS66 patients were studied with newly diagnosed primary bladder cancer (T(a) = 12, T(1) = 26, T(2) = 11, T(3) = 10, T(4) = 7; G(1) = 35, G(2) = 19, G(3) = 12). No patient was treated preoperatively with either radiation or chemotherapy. Reverse transcription-polymerase chain reaction (RT-PCR) was performed for measure of mRNA expression for LRP, multidrug-resistance gene 1 (MDR1), and multidrug resist nce-associated protein 1 (MRP1). Expressions of LRP, P53 and P63 proteins were examined by immunohistochemistry staining.

RESULTSLRP mRNA had the highest expression rate (64%, 42/66) among three MDR markers in primary bladder cancers without chemotherapy and its level was significantly higher in normal bladder tissue than in TCC of bladder (t = 2.82, P < 0.01), in low grade than in high grade cancers (t = 4.14, P < 0.01), and in superficial than in invasive cancers (t = 3.58, P < 0.05). LRP mRNA expression showed no correlation with either MDR1 or MRP1, but close correlation with LRP protein level (r = 0.89, P < 0.01). LRP was associated with low-grade (r = 0.81, P < 0.01) and low-stage (r = 0.78, P < 0.05) cancers, but not with tumor suppressor P53 or P63 (P > 0.05).

CONCLUSIONSThe grade and stage-related expression pattern of LRP indicates that it may be a predictive index for intrinsic MDR in bladder cancer. Anti-cancer drugs out of the MDR spectrum of LRP may be more effective for patients with early bladder cancer.

ATP-Binding Cassette, Sub-Family B, Member 1 ; biosynthesis ; genetics ; Adult ; Aged ; Carcinoma, Transitional Cell ; genetics ; metabolism ; pathology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Multidrug Resistance-Associated Proteins ; biosynthesis ; genetics ; Neoplasm Proteins ; biosynthesis ; genetics ; RNA, Messenger ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Urinary Bladder Neoplasms ; genetics ; metabolism ; pathology ; Vault Ribonucleoprotein Particles ; biosynthesis ; genetics

OBJECTIVETo evaluate the roles of cell adhesion, multidrug resistance and cell proliferation in short-term recurrent cases with superficial bladder cancer, and the prognostic value of the three indexes.

METHODSImmunohistochemical staining for E-cad, P-gp and Ki-67 was performed on the tumors of 100 patients with stage T0-T1 transitional cell carcinoma of the bladder who had been included in a retrospective research by follow-up.

RESULTSE-cad and P-gp expression was positive in 51 (43.2%)and 17 (14.4%) of the tumors, respectively and mean proliferation index (PI) was 22.1%. The decrease in E-cad expression was accompanied with the increasing recurrent episodes (P < 0.05), while increase of P-gp expression and PI were accompanied with the increasing recurrence episodes (P < 0.05). There was significant difference according to E-cad, P-gp positivity and between T(1)G(3) patients and no-T(1)G(3) patients (P < 0.05). There was negative correlation of E-cad expression with P-gp expression and PI.

CONCLUSIONSMinimum adhesion, strong drug resistance and maximum proliferation are the main factors that promote short-term recurrence of superficial bladder cancer and also the inherent reasons for easy recurrence and high malignancy of T(1)G(3) tumors. During this course, the three aspects may interact.

ATP-Binding Cassette, Sub-Family B, Member 1 ; analysis ; Adult ; Cadherins ; analysis ; Cell Adhesion ; Cell Division ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Female ; Humans ; Ki-67 Antigen ; analysis ; Male ; Neoplasm Recurrence, Local ; etiology ; Urinary Bladder Neoplasms ; drug therapy ; etiology ; pathology

Acute Disease ; Adult ; Altitude Sickness ; blood ; enzymology ; Glutathione ; blood ; Glutathione Peroxidase ; blood ; Humans ; Lipid Peroxidation ; Male ; Military Personnel ; Nitric Oxide ; blood ; Nitric Oxide Synthase ; blood ; Oxidoreductases ; metabolism ; Superoxide Dismutase ; blood

OBJECTIVETo construct recombinant adenovirus containing codon-modified HPV16L1 gene, and evaluate systemic and mucosal immunological responses induced after immunization with the recombinant virus.

METHODSThe recombinant adenovirus rAd-mod.HPV16L1 was constructed by Admax kit. The C57 BL/6 mice were immunized by purified rAd-mod.HPV16L1 through different inoculation routes. The immunological effect was evaluated by testing the specific neutralizing antibodies in sera and vaginal secretions of immunized mice through indirect ELISA and neutralization assay based HPV pseudovirus.

RESULTSThe result showed that intramuscular immunization could induce good systemic immunity, but the mucosal immunity was too weak, and immunization via intranasal route could induce satisfactory immunity both in sera and vaginal secretions, while intravaginal immunization failed to induce any specific immunological responses either in sera or vaginal secretions.

CONCLUSIONThe recombinant adenovirus containing codon- modified HPV16L1 gene was successfully constructed. Immunization through intranasal route could induce satisfactory immunity both in sera and vaginal secretions, while intramuscular immunization could only induce high titer of neutralizing antibodies in sera.

Adenoviridae ; genetics ; Animals ; Antibodies, Viral ; analysis ; immunology ; Antibody Specificity ; Capsid Proteins ; genetics ; immunology ; Codon ; genetics ; DNA, Recombinant ; genetics ; Female ; Genetic Engineering ; Human papillomavirus 16 ; genetics ; immunology ; Mice ; Mice, Inbred C57BL ; Oncogene Proteins, Viral ; genetics ; immunology ; Vaccination

AIM:To explore the effect of Wnt/β-catenin signaling pathway in airway smooth muscle cells (ASMC) on asthmatic airway remodeling.METHODS:The asthmatic airway remodeling model in rats was established and the ASMC was isolated and cultured.The protein expression of β-catenin,glycogen synthase kinase-3β (GSK-3β),cMyc and cyclin D1 in the ASMC was determined by Western blot.After depressing the interaction between β-catenin and p300/CBP,the cell activity was measured by CCK-8 assay and the change of cell cycle distribution was analyzed by flow cytometry.Meanwhile,the protein expression of c-Myc and cyclin D1 in the ASMC was determined by Western blot after inhibiting P38 mitogen-activated protein kinase (MAPK) activity.RESULTS:The protein levels of β-catenin,c-Myc and cyclin D1 were significantly increased in asthma group while the protein level of GSK-3β was decreased in the same group (P ＜ 0.05).After depressing the interaction between β-catenin and p300/CBP,the cell activity of ASMC was decreased in asthma group compared with control group (P ＜ 0.05),and the change of the cell cycle distribution in asthma group was also more obvious (P ＜ 0.05).After inhibiting P38 MAPK activity,the protein levels of c-Myc and cyclin D1 were all decreased compared with control group in ASMC asthma and control rats (P ＜ 0.05).CONCLUSION:Wnt/β-catenin signaling pathway may participates in airway remodeling in asthma by increasing the protein expression of c-Myc and cyclin D1,reacting with the P38 MAPK signaling pathway and regulating the growth of ASMC.

The aim of the research is to investigate the genetic characteristics of Legionella pneumophila serogroup1 (LP1)in Sichuan Province.The sequence-based typing (SBT) and multiple-locus VNTR analysis (MLVA) were used to describe the genetic polymorphism of 42 strains which were isolated from 1989-2016 in Sichuan Province,China.According to the reference,PCR was used to detect the 8-VNTR loci and 7 housekeeping genes respectively.The VNTR results were determined by using capillary electrophoresis,and the SBT results were sequenced and compared with the database of EWGLI.Results showed that totally 42 stains were divided into 8 MLVA types with the advantage types were M08 (47.6 ％) and M07 (23.8 ％).Twelve ST types were obtained with 3 main clonal complex and 2 singleton,including 2 novel ST types,among those,ST1 was the predominant type,accounting for 52.3 ％,following by ST630 (14.2 ％).In conclusion,our results demonstrated MLVA and SBT were both applied to the research for molecular epidemiological investigation of LP1 and showed the high genetic polymorphism and the regional specificity.The results also suggest that the isolates are a potential threat to the public,effective control and prevention strategies are urgently needed.

OBJECTIVETo explore the expression and clinical significance of Semaphorin4D (Sema4D) mRNA in peripheral blood lymphocyte, Sema4D on platelet surface, soluble Sema4D (sSema4D) in plasma in patients with cerebral infarction.

METHODSTaking 299 patients with cerebral infarction as the case group while 195 healthy adults as the control group. The mRNA expression of Sema4D was detected by Real-time PCR, and Sema4D expression on platelet by flow cytometry, sSema4D by ELISA. Then, the expression of Sema4D on platelet surface and the concentration of sSema4D in plasma of the 195 selected patients following 2 weeks' treatment were tested.

RESULTSThe expression of Sema4D mRNA significantly increased in the case group \[(2.23, 2.66)×10(4) IU/ml\] than in the control group \[(0.49, 0.53)×10(4)IU/ml\] (P < 0.01). The level of Sema4D on platelet surface in the case group (191.62 ± 46.56) significantly decreased than in the control group (303.33 ± 112.66) (P < 0.01). But the concentration of sSema4D in plasma in the case group \[(1.34 ± 0.56) µg/L\] was obviously higher than in the control group \[(0.61 ± 0.31) µg/L\] (P < 0.01). The expression of Sema4D on platelet was obviously relevant with the concentration of sSema4D in plasma in the case group with the correlation coefficient as 0.328 (P < 0.01). The expression of Sema4D on platelet obviously peaked up following 2 weeks' routine therapy in the case group, which was close to that in the control group. Meanwhile the concentration of sSema4D in plasma was downward corrected to the normal in the case group.

CONCLUSIONThe increased expressions and plasma levels, and reduced expressions on platelet of Sema4D in acute period, which returned to normal 2 weeks after treatment in the case group may be related to the occurrence of acute cerebral infarction, reflecting the development process of cerebral infarction.

Aged ; Antigens, CD ; blood ; metabolism ; Blood Platelets ; metabolism ; Case-Control Studies ; Cerebral Infarction ; blood ; Female ; Humans ; Lymphocytes ; metabolism ; Male ; Middle Aged ; Semaphorins ; blood ; metabolism

Low birth weight (LBW) and preterm birth (PB) are associated with newborn mortality and diseases in adulthood.We explored factors related to LBW and PB by conducting a population-based case-control study from January 2011 to December 2013 in Wuhan,China.A total of 337 LBW newborn babies,472 PB babies,and 708 babies with normal birth weights and born from term pregnancies were included in this study.Information of newborns and their parents was collected by trained investigators using questionnaires and referring to medical records.Univariate and logistic regression analyses with the stepwise selection method were used to determine the associations of related factors with LBW and PB.Results showed that maternal hypertension (OR=6.78,95％ CI:2.27-20.29,P=0.001),maternal high-risk pregnancy (OR=1.53,95％ CI:1.06-2.21,P=0.022),and maternal fruit intake ≥300 g per day during the first trimester (OR=1.70,95％ CI:1.17-2.45,P=0.005) were associated with LBW.BMI ≥24 kg/m2 of mother prior to delivery (OR=0.48,95％ CI:0.32-0.74,P=0.001) and gestation ≥37 weeks (OR=0.01,95％ CI:0.00-0.02,P＜0.034) were protective factors for LBW.Maternal hypertension (OR=3.36,95％ CI:1.26-8.98,P=0.016),maternal high-risk pregnancy (OR=4.38,95％ CI:3.26-5.88,P＜0.001),maternal meal intake of only twice per day (OR=1.88,95％ CI:1.10-3.20,P=0.021),and mother liking food with lots of aginomoto and salt (OR=1.60,95％ CI:1.02-2.51,P=0.040) were risk factors for PB.BMI ≥24 kg/m2 of mother prior to delivery (OR=0.66,95％ CI:0.47-0.93,P=0.018),distance of house from road ≥36 meters (OR=0.72,95％ CI:0.53-0.97,P=0.028),and living in rural area (OR=0.60,95％ CI:0.37-0.99,P=0.047) were protective factors for PB.Our study demonstrated some risk factors and protective factors for LBW and PB,and provided valuable information for the prevention of the conditions among newborns.

OBJECTIVETo evaluate the immune potency of recombinant adenovirus combined with rAAV1 vector expressing HPV16L1 protein in mice.

METHODSThe rAdV and rAAV1 vector containing codon-modified HPV16L1 gene was constructed using Admax and AAVmax packaging system respectively. C57 BL/6 mice were immunized with purified rAdV and rAAV1 vector through intramuscular and intranasal inoculation routes, and the titer of neutralizing antibody was determined by neutralization assay based HPV16 pseudovirus.

RESULTSIntramuscular immunization by rAAV1-mod. HPV16L1 or combined with rAd-mod. HPV16L1 can induce higher titer of neutralizing antibody in serum than that of other groups. The titer of neutralizing antibody of intranasal groups is significantly lower than that of intramuscular group, although the prime-boost strategy using in intranasal group was effective to enhance the specific humoral immunity.

CONCLUSIONThe rAAV1-mod. HPV16L1 combined with rAd-mod. HPV16L1 can induce higher titer of neutralizing antibody in serum through intramuscular route than that of other groups at the 16th week after the first immunization.

Adenoviridae ; genetics ; immunology ; Adenoviridae Infections ; immunology ; Animals ; Antibodies, Viral ; immunology ; Dependovirus ; genetics ; immunology ; Immune System Phenomena ; Immunization ; Mice ; Mice, Inbred C57BL ; Oncogene Proteins, Fusion ; immunology ; Oncogene Proteins, Viral ; immunology ; Recombinant Proteins ; genetics ; immunology

To investigate the feasibility of using recombinant adeno-associated virus type 1 vector as prophylactic vaccine against HPV16 infection, rAAV1-mod. HPV16L1, the recombinant AAV1 vector containing codon-modified HPV16 L1 gene, was constructed. C57BL/6 mice were immunized with purified rAAV1 vector through intramuscular and intranasal inoculation routes, and the titer of neutralizing antibody was determined by neutralization assay based on HPV16 pseudovirus. The result shows that the single dose of rAAV1-mod. HPV16L1 can induce specific neutralizing antibody in serum through both inoculation routes. Compared with intranasal group, intramuscular group can induce higher titer of neutralizing antibody. Eliciting strong and prolonged neutralizing antibody in serum, the rAAV1-mod. HPV16L1 is one of promising HPV16 prophylactic vaccine candidates.
Animals ; Antibodies, Viral ; blood ; Capsid Proteins ; genetics ; immunology ; Dependovirus ; genetics ; Female ; Mice ; Mice, Inbred C57BL ; Oncogene Proteins, Viral ; genetics ; immunology ; Papillomavirus Vaccines ; administration & dosage ; immunology ; Vaccination ; Vaccines, Synthetic ; administration & dosage ; immunology