Inositol requiring enzyme 1 alpha (IRE1α), a widespread transmembrane protein in mammals, is an endoplasmic reticulum stress (ER stress) receptor. Among the three signaling pathways of the unfolded protein response (UPR), the IRE1α pathway is the most conservative. And there is a growing body of evidence that the occurrence and development of tumors is closely related to the over-expression of IRE1α. Therefore, the study of the IRE1α inhibitors is of great significance to the discovery of new anti-tumor drugs and has been attracting more and more attention. In the hope of providing ideas for the research of targeting IRE1α for cancer therapy, this paper reviewed the data of representative IRE1α inhibitors, including inhibitory activity, the mechanism of action, structural characteristics, and so on.

Experimental acute serum sickness was produced in 20 rabbits By a sensitizing injection with bovine serum albumin (BSA) through the auricular vein. Five days after the sensitization, ten of the 20 animals were given a total body irradiation of 300 r from a 60Co sourse. No radiation was given to the other 10 animals which served as controls. Blood samples were taken from the rabbits of both groups before and 2 , 4 , 6 , 8 , 10, 12, 14, and 16 days after antigen injection. After the sera were seperated, the concentrations of the circulating immune complexes were determined with the PEG complement consumption test. It was found that the dynamic curves of the concentrations of the circulating immune complexes of the two groups were essentially similar. This result strongly suggests that total body irradiation of gamma rays given five days after the sensitization of an antigen exerts no influence on the formation of the circulating immune complexes though acute radiation sickness is well established.

Objective To explore if bacillus bifidus relieve CPFX-induced testosterone reduction in mouse testes.Methods Twenty-four male mices were divided into 4 groups, then administered saline for 6 days (Sal6 group), CPFX for 6 days (A6 group), CPFX for 6 days followed by bifidobacteria treatment for the next 6 days (A6+P6 group), CPFX for 6 days and then saline for the next 6 days (A6+Sal6 group).We detected serum levels of testosterone by RIA, as well as levels of steroidogenic enzymes mRNA [cholesterol side-chain cleavage enzyme (P450scc) and steroidogenic acute regulatory protein (StAR)] and NF-E2-related factor2 (Nrf2) mRNA in testes by real-time PCR, Nrf2, heme oxygenase-1 (HO-1), and 4-hydroxy-2-nonenal (4-HNE) by Western blot and4-HNE by Immunohistochemistry.Results The A6 group had significantly lower serum testosterone levels compared with the Sal6 group (P<0.001), the A6+P6 group had significantly higher compared with the A6 (P<0.001) and A6+Sal6 groups (P<0.01).The A6 group had significantly lower StAR mRNA compared with the Sal6 group (P<0.001), the A6+P6 group had significantly higher level compared with the A6 (P<0.01) and A6+Sal6 groups (P<0.01).The A6 group had significantly lower P450scc mRNA as compared with the Sal6 group (P<0.001), the A6+P6 group had significantly higher compared with the A6 (P<0.001) and A6+Sal6 groups (P<0.05).The A6 group had significantly lower Nrf2 compared with the Sal6 group (P<0.001), the A6+P6 group had significantly higher compared with the A6(P<0.01) and A6+Sal6 groups (P<0.05).The A6 group higher 4-HNE expression compared with the Sal6 group, the A6+P6 group had significantly lower compared with the A6 (P<0.01) and A6+Sal6 groups (P<0.05).Conclusions Bifidobacteria the reduction of CPFX-induced testosterone reduction, and these effects may potentially explained by Nrf2 inflammatory signaling pathway.

Objective To investigate the diagnostic value of transbronchial lung biopsy (TBLB) under virtual bronchoscopic navigation (direct path), endobronchial ultrasonography with a guide sheath (GS) and rapid on-site evaluation (ROSE) for solitary pulmonary nodules (SPNs). Methods One hundred and seventy-eight patients who were underwent transbronchial lung biopsy in the Tianjin Medical University General Hospital between January 2015 to December 2016 were retrospectively evaluated. CT images of all patients showed solitary pulmonary nodules surrounded by lung tissue, and ROSE was undergone during the procedure. The patients were divided into conventional (C-TBLB) group, virtual bronchoscopic navigation (VBN) group, endobronchial ultrasonography with a guide sheath (GS) group, and virtual bronchoscopic navigation combined with endobronchial ultrasonography with a guide sheath group (combination) depending on the different devices. The diagnostic yield and the location or the effect of lesion on the diagnostic rate were compared between four groups. The coincidence rate of ROSE and the histopathological findings of TBLB were compared. The value of ROSE for the early diagnosis of disease was further evaluated. Results The diagnostic rates were 32.5％(13/40), 66.7％(24/36), 68.2％(30/44) and 75.8％(44/58) for C-TBLB group, VBN group, GS group and combination group, respectively. There were significant differences in diagnostic rates between C-TBLB group and other tree groups (χ2=8.853, 10.677 and 18.293, P<0.008). But there were no significant differences in diagnostic rates between VBN group, GS group and combination group (P>0.008). The diagnostic rates for peripheral pulmonary nodules were 12.5％ (2/16), 42.9％ (6/14), 40.0％ (4/10) and 75.9％(22/29) in C-TBLB group, VBN group, GS group and combination group. The diagnostic rate was significantly higher in combination group than that of other three groups (χ2=17.434, P<0.05). The result of ROSE was consistent with result of histopathology (Kappa = 0.775, P<0.001). The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of ROSE during transbronchial biopsy for solitary pulmonary nodules were 90.7％, 87.0％, 86.7％, 90.9％ and 88.8％, respectively. No pneumothorax, hemoptysis or other serious complications were found in patients. Conclusion Virtual bronchoscopic navigation, endobronchial ultrasonography with a guide sheath for solitary pulmonary nodules by transbronchial lung biopsy can improve the diagnostic rate of solitary pulmonary nodules.

OBJECTIVE To evaluate the use of antibiotics after coronary artery bypass.METHODS Forty patients were assigned into two groups,vancomycin group and cefradine group.Each included 20 patients.We compared the infection cases,cost of hospitalization,and cost of medicine after CABG.RESULTS There were no difference of(infection) between two groups,the cost of hospitalization was fewer in cefradine group.(CONCLUSIONS) The short-term use of cefradine after CABG could achieve the goals of preventing infection of CABG,and save medical resources.

Background The pathogenesiof age-related maculadegeneration (AMD) iassociated with the senility of human retinal pigmenepithelium (RPE) cells.Seeking drug to arresRPE cell senility iof significance fothe prevention and treatmenof AMD.Research showed thathe lycium barbarum polysaccharide (LBP) can delay senility,buitinfluence on RPE cell aging iunclear.Objective Thistudy wato discusthe protective effecand mechanism of LBP on RPE cell aging.MethodPorcine retinal neural epithelial layewaisolated,and photoreceptooutesegmen(POS) waextracted by density gradiencentrifugation and marked by FITC.The POwathen co-cultured with RPE cellin the medium containing 0.01,0.10 and 1.00 g/L LBP fo24 hours.The areof fluorescence,representing the amounof POphagocytosed by RPE cells,wameasured undethe fluorescenmicroscope to evaluate the influence of LBP on the phagocytifunction of RPE cells.The POS-induced RPE lipofuscin-uptake cell model waestablished by co-culturing human RPE cellwith porcine POfo3 weeks.The RPE-POco-culture cell model waincubated in medium containing 0.01,0.10 o1.00 g/L LBP,and the autofluorescence caused by lipofuscin up-taken into RPE cellwadetected with flow cytometry.cell counting kiwaused to assescell proliferation and viability (value) 24,48 and 72 hourafteculturing.ResultPorcine POpresented athin rodundethe lighmicroscope and appeared abilayedisc-like structureundethe transmission electron microscope,and itFITC-labeled yellow-green autofluorescence waobserved undethe fluorescenmicroscope.No POwaup-taken into the RPE cellin the normal control group,buthe areof POphagocytosed by RPE cellwagradually enlarged with increasing doseof LBP,showing significandifference among the group(F =21.425,P =0.006).Compared with the POcontrol group,the phagocytosed areincreased avariouconcentrationof LBP+POgroup(P＜0.01).Flow cytometry showed thathe autofluorescence value in the POcontrol group wamore highethan thaof the normal control group.Athe LBP dose increased,the autofluorescence value in the RPE celldeclined gradually and iwaneathe normal value in the 1.00 g/L LBP+ POgroup.The rate of proliferation of the lipofuscin RPE cellvaried with the increase of doseof LBP with the maximal value in the normal RPE group and minimal value in the lipofuscin RPE group,and the rate of proliferation of the lipofuscin RPE cellascended with increasing doseof LBP until neathe normal value in the 1.00 g/L LBP + lipofuscin RPE cellgroup (P＞0.05).ConclusionLBP enhance the anti-aging effecof human RPE cellby strengthening the phagocytiability to POand the ability to remove lipofuscin and by heightening the proliferation of human RPE cells.

The known members of inhibitor of growth (ING) gene family are considered as candidate tumor suppressor genes. ING4, a novel member of ING family, is recently reported to regulate brain tumour angiogenesis through transcriptional repression of NF-?B-responsive genes, induce G2/M arrest by the increased p21 expression in a p53-dependent manner, suppress the loss of contact inhibition and represses activation of the hypoxia inducible factor, which plays an important role in the progression of tumorigenesis. However, seldom studies about ING4 inducing tumor cells apoptosis were reported.The C6 cells (mouse glioma cells) were infected respectively with the blank adenovirus carrying GFP (Ad) and the recombinated Ad-hING4-His, then RT-PCR assay was used to detect the transcriptions of hING4, as well Western-blotting assay was ued to detect the expressions of hING4. The effects of hING4 expression upon C6 cells were observed, and the growth curve was drawed and tumor control rates were calculated. The C6 cells, which were affected by blank Ad and Ad-hING4-His, were respectively observed by LSCM (laser scan confocal microscope) and transmission electron microscope (TEM), detected by flow cytometry; and the genomic DNA of both groups were extracted and electrophoresised in agarose gel to examinate the DNA fragments. The results showed hING4 can significantly inhibit the growth of C6 cells by promoting the cell’s apoptosis, which probably is the first one to prove this property of ING4.The experimental and theoretical foundation for gene therapy for gliomas with ING4 in the future was established.

OBJECTIVE: To observe the expression of discs large homolog 4 (DLG4) protein in hippocampus, amygdala and frontal cortex of rats and evaluate postsynaptic density in heroin dependence. METHODS: The rat heroin dependent model was established by increasing intraperitoneal injection of heroin. DLG4 proteins in hippocampus, amygdala and frontal cortex of heroin dependent 9, 18, 36 days rats were detected with immunohistochemical staining and compared with that in the control group. RESULTS: DLG4 proteins in hippocampus, amygdala and frontal cortex were gradually reduced with extension of heroin dependent time. CONCLUSION Heroin dependence can affect postsynaptic density of hippocampus, amygdala and frontal cortex. The changes become more apparent with extension of heroin dependence time.
Amygdala/metabolism* ; Animals ; Disks Large Homolog 4 Protein ; Frontal Lobe/metabolism* ; Heroin/pharmacology* ; Heroin Dependence ; Hippocampus/metabolism* ; Injections, Intraperitoneal ; Intracellular Signaling Peptides and Proteins/metabolism* ; Membrane Proteins/metabolism* ; Rats

Objective To investigate the changes of serum IL-1β,IL-6 ,TNF-α,NGF and BDNF levels and their correlation with clinical symptoms of schizophrenia inpatiens and their value in the auxiliary diagnosis of schizophrenia .Methods The case-control study was used .The levels of serum IL-1β,IL-6 ,TNF-α,NGF and BDNF were measured by using the enzyme linked immunosorbent assay(ELISA) in 85 inpatients with schizophrenia and 85 healthy controls .Their changes in the case group were compared between before treatment and after 3-month treatment .The Pearson correlation analysis was used to analyze the correlation between the lev-els of IL-1β,IL-6 ,TNF-α,NGF and BDNF with the positive and negative syndrome scale (PANSS) score and the auxiliary diagnosis value of serum cytokine and neurotrophic factor levels were evaluated with the receiver operating characteristic (ROC) curve .Re-sults The levels of serum IL-1β(t=4 .560) ,IL-6(t= 4 .957) and TNF-α(t= 4 .799) before treatment in the schizophrenia case group were significantly higher than those in control group ,while the NGF(t= -4 .806) and BDNF(t= -4 .881) levels were sig-nificantly lower than those in the control group ,the differences were statistically significant (P<0 .01) .After 3-month treatment , the levels of serum IL-1β(t=4 .543) ,IL-6(t=4 .327) and TNF-α(t=4 .654) in the schizophrenia case group were significantly de-creased compared with before treatment ,while the NGF(t= -4 .641) and BDNF(t= -4 .876) levels were significantly increased , the differences were statistically significant (P< 0 .01) .IL-1β was positively correlated with the positive symptoms scores (r=0 .325 ,P<0 .01) ,IL-6 was positively correlated with the negative symptoms scores (r=0 .319 ,P<0 .01) ,TNF-α was positively correlated with the positive symptoms scores (r= 0 .281 ,P< 0 .01) ,NGF was negatively correlated with the positive symptoms scores(r= -0 .229 ,P<0 .05) ,BDNF was negatively correlated with the positive symptoms scores (r= -0 .272 ,P< 0 .05) .The cut-off values of serum IL-1β,IL-6 ,TNF-α,NGF and BDNF in the auxiliary diagnosis of schizophrenia were 40 .083 ,20 .037 ,17 .115 ,19 .998 ,584 .157pg/mL respectively ,the corresponding areas under the ROC were 0 .723 ,0 .772 ,0 .686 ,0 .712 and 0 .708 respectively ,the sensitivities were 0 .565 ,0 .871 ,0 .894 ,0 .859 and 0 .729 respectively ,and the specificities were 0 .871 ,0 .565 ,0 . 365 ,0 .494 and 0 .624 respectively .Conclusion The levels of serum IL-1 ,IL-6 ,TNF-α,NGF and BDNF have the correlation with the clinical symptoms of schizophrenic inpatients and have a certain value in the auxiliary diagnosis of schizophrenia .

Objective To investigate the expression of peroxiredoxin 1 (Prx 1) in hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) and to evaluate the relationship between the expressions of Prx 1 and the postoperative recurrence of this disease. Methods Immunohisto chemistry and Western blotting were performed to examine the expression of Prx 1 protein in 40 patients with HCC with PVTT. Experiments on Sprague Dawley (SD) rat hepatoma model were further carried out to observe the pathological changes of Prx 1 by immunohistochemistry. Clinical outcomes were analyzed to find a correlation between the recurrence and positive rate of Prx 1. Results The expression level of Prx 1 was significantly up-regulated in primary tumor tissues than in tumor thrombosis samples (P＜0.01). Immunohistochemistry results showed that the positive rate of Prx 1 in primary tumor tissues were higher than that in tumor thrombosis. Western blotting confirmed a same trend in the level of Prx 1, the average luminosity of the blots were 1534.2 and 735.6, respectively. There was a significant difference in SD rat hepatoma model, the 4, 8, 12, 16, 20 and 24-week positive rates of Prx 1 in liver tumor tissues were 60%, 80%, 75% ,65%, 40% and 25% respectively. Clinical outcomes showed that the time to first postoperative recurrence of Prx 1 in the primary tumor positive group was significantly higher than that in the negative group (6. 3 vs 3. 7 months, P＜0. 01). Conclusions Prx 1 protein was down-regulated in HCC with PVTT. There was a negative correlation between the expression of Prx 1 and recurrence.