ABSTRACT
OBJECTIVE To study the pharmacological basis of Schisandra chinensis in the treatment of allergic asthma. METHODS The common components of 10 batches of S. chinensis from different habitats were analyzed by UPLC-Q-TOF-MS/MS. Furthermore， the allergic asthma model was established by intraperitoneal injection of ovalbumin （OVA） and aluminum hydroxide for stimulation combined with atomization exitation； general behavioral observation and the contents of interferon γ （IFN-γ）， interleukin-4 （IL-4） and immunoglobulin E （IgE） in serum were taken as criteria for evaluating the therapeutic effect of S. chinensis from different habitats in the treatment of allergic asthma. Correlation coefficients between common peak area and efficacy evaluation index of each batch of medicinal material were analyzed through grey correlation degree and Pearson correlation analysis. RESULTS A total of 21 common components were identified in 10 batches of S. chinensis from different habitats. After administration of S. chinensis， symptoms such as shortness of breath， sneezing and curling of rats were alleviated. In addition， the content of IFN-γ was significantly increased while the contents of IL-4 and IgE in serum were distinctly decreased （P＜0.01）. Grey correlation analysis showed that 11 common components had high correlation coefficients with IFN-γ， IL-4 and IgE （rˉ＞0.8）. Pearson correlation analysis showed that 8 components were significantly positively correlated with the content of IFN-γ （P＜ 0.05）， and 9， 8 components were significantly negatively correlated with the content of IL-4 and IgE （P＜0.05）. Based on the results of grey correlation degree and Pearson correlation analysis， 7 components such as peak 3， 4， 6， 7， 9， 19 and 20， were highly related to S. chinensis in the treatment of allergic asthma. CONCLUSIONS Schisandrol A， schisandrin B， schisandrin C， gomisin M2， gomisin J， pregomisin and angeloylgomisin H are the potential pharmacodynamic substance basis of S. chinensis in the treatment of allergic asthma.
ABSTRACT
Objective:To investigate the effects of family integrated care(FICare) on positive feelings and readiness for hospital discharge among mothers of premature.Methods:From January to October 2021, a total of 100 premature infants were admitted to the neonatal intensive care unit(NICU) of General Hospital of Ningxia Medical University, and their mothers were admitted to this program.They were divided into research group (52 cases) and control group (48 cases) randomly.The premature infants in the control group received NICU routine care during hospitalization, meanwhile the premature infants and the mothers in the research group were given FICare on the routine care during hospitalization.On the 2nd day of admission (before the intervention) and 1 day before discharge (after the intervention), the positive aspects of caregiver (PAC) and the readiness for hospital discharge scale (RHDS) were used to evaluate the positive feelings and readiness for discharge of premature infants' mothers in the two groups.The t-test of two independent samples was used for measurement data between the two groups, and the paired t-test was used for intra-group comparison by SPSS 22.0 statistical software.The comparison of enumeration data between the two groups was carried out by chi-square test. Results:There were no significant differences in the scores of PAC and discharge readiness (both P>0.05) between the two groups before intervention.After the intervention, the premature mothers' total score of PAC in the research group and control group were((32.00±2.79), (27.40±3.37)), the self-affirmation dimension were ((18.55±2.39), (16.10±1.77)), the life outlook dimension were( (13.45±1.93), (11.30±2.20)), and all the scores in the research group were higher than those of the control group (all P<0.05). The total scores of readiness for hospital discharge in the research group and control group were ((106.75±6.11), (100.40±10.41)), personal status dimension were ((26.92±2.37), (25.11±3.32)), adaptability dimension were ((43.50±2.70), (40.64±4.65)), and the anticipatory support dimension were ((36.33±2.16), (34.29±3.29)). The total scores and each dimensions of the mothers' readiness for hospital discharge in the research group were higher than those in the control group (all P<0.05). After the intervention, the positive feeling total score and all dimensions score of the two groups of premature mothers were higher than before intervention (all P<0.05). After intervention, the total score of readiness for hospital discharge and the scores of all dimensions of premature mothers in the research group were higher than before intervention (all P<0.05). And there were no significant difference in the total scores of readiness for hospital discharge and other dimensions in the control group comparison before and after intervention(all P>0.05), except adaptability dimensions ( P<0.05). Conclusion:The findings suggest that FICare can improve the positive feelings of mothers of premature infants and hospital discharge readiness especially.
ABSTRACT
Pancreaticoduodenectomy is cumbersome and difficult to operate,with a long operative time and high risk of postoperative complications,thus it is one of the most complicated operations among general surgery.With the popularization and progress of minimally invasive techniques,minimally invasive pancreaticoduodenectomy (MIPD) has obtained a well developing.It has been confirmed that MIPD is noninferior or even superior to the traditional open pancreaticoduodenectomy in term of the feasibility,safety and effects of radical cure.However,the relevant conclusions are mostly from single-center retrospective studies,without high-quality evidence support.The authors has reviewed the recent research progress of MIPD in the indications and contraindications,safety,feasibility and tumor curative effect,and illustrated the current status and prospects of MIPD with clinical experience and related literature,contributing to the standardization of MIPD in China.
ABSTRACT
Objective To investigate the relationship of lymph node metastasis rate (LNR) with prognosis of esophageal squamous cell carcinoma after radical resection and postoperative adjuvant chemotherapy.Methods The retrospective case-control study was conducted.The clinicopathological data of 121 patients who underwent radical resection of esophageal squamous cell carcinoma in the Peking University Cancer Hospital from January 2012 to September 2016 were collected.There were 105 males and 16 females,aged from 42 to 76 years,with a median age of 58 years.All patients underwent radical resection of esophageal cancer with at least two-field lymph nodes dissection.Some patients underwent corresponding chemotherapy and radiotherapy.The thoracic and abdominal lymph nodes were grouped according to the 7th edition standard of Americau Joint Committee on Cancer (AJCC).The lymph nodes dissected were labeled in groups,and all the lymph nodes were examined by pathology test.Observation indicators:(1) follow-up;(2) effects of LNR on prognosis of patients in different AJCC N staging;(3) relationship between LNR and postoperative adjuvant chemotherapy.Follow-up was conducted by outpatient examination,telephone interview and hospital statistical office to detect postoperative survival of patients up to February 2017.The disease-free survival time was from surgery date to date of confirmation of tumor recurrence,and the overall survival time was from surgery date to death of the patient or the last follow-up date.Measurement data with skewed distribution were expressed by M (range).The Kaplan-Meier method was used to calculate the survival rate and draw the survival curve.The Log-rank test was used for survival analysis.Results (1) Follow-up:121 patients were followed up for 3.0-94.2 months,with a median follow-up time of 27.1 months.During the follow-up,98 of 121 patients had tumor recurrence and metastasis (including 64 deaths),22 had no metastasis,and 1 had unknown tumor metastasis.The mean overall survival time of patients was 30.8 months.The 1-,3-,5-year disease-free survival rates were 47.1％,20.3％,and 5.9％,respectively.The 1-,3-,5-year overall survival rates were 93.1％,48.7％,and 35.3％,respectively.(2) Effects of LNR on prognosis of patients in different AJCC N staging:of 121 patients,46 were in N0 stage,42 were in N1 stage,28 were in N2 stage,and 5 were in N3 stage.Of 42 patients in N1 stage,35 with 0 ＜ LNR ≤ 0.15 had a disease-free survival time of 12.2 months (range,1.2-82.3 months),and 7 with LNR ＞ 0.15 had a disease-free survival time of 6.9 months (range,2.1-23.1 months);the difference between the two groups was statistically significant (x2 =3.888,P＜0.05).Of the 28 patients in N2 stage,12 with 0 ＜ LNR ≤ 0.15 had a disease-free survival time of 8.5 months (range,1.2-38.8 months),and 16 with LNR ＞ 0.15 had a disease-free survival time of 4.4 months (range,1.0-52.7 months);the difference was not statistically significant (x2 =0.007,P＞0.05).Forty-six patients in N0 stage were detected no lymph node metastasis,and only 5 cases were in N3 stage,with no analysis.(3) Relationship between LNR and postoperative adjuvant chemotherapy:of the 121 patients,56 underwent postoperative adjuvant chemotherapy,which was mainly constituted by pactitaxel,platinum,and 5-fluorouracilbased regimens,58 didn't undergo postoperative adjuvant chemotherapy,and 7 had unknown data of postoperative adjuvant chemotherapy.Of 121 patients,46 had LNR =0,47 had 0 ＜ LNR ≤ 0.15,28 had LNR ＞ 0.15.Of the 46 patients with LNR =0,17 who underwent postoperative adjuvant chemotherapy had a disease-free survival time of 8.1 months (range,3.9-66.7 months) and a overall survival time of 34.0 months (range,4.7-76.0 months);29 who didn't undergo postoperative adjuvant chemotherapy had a disease-free survival time of 18.8 months (range,1.6-53.2 months),and a overall survival time of 48.6 months (range,8.3-94.2 months);there was no significant difference in the disease-free survival time and overall survival time between the two groups (x2=0.311,0.858,P＞0.05).Of the 47 patients with 0 ＜ LNR ≤ 0.15,27 who underwent postoperative adjuvant chemotherapy had a disease-free survival time of 13.3 months (range,5.0-82.3 months),and a overall survival time of 53.1 months (range,5.7-82.3 months);20 without postoperative adjuvant chemotherapy had a disease-free survival time of 8.4 months (range,1.2-39.2 months),and a overall survival time of 26.5 months (range,5.9-52.6 months).There were significant differences in the disease-free survival time and overall survival time between the two groups (x2 =10.322,4.971,P＜0.05).Of the 28 patients with LNR ＞ 0.15 (7 had unknown data of postoperative adjuvant chemotherapy),12 who underwent adjuvant chemotherapy had a diseasefree survival time of 10.3 months (range,2.9-52.7 months),and a overall survival time of 29.5 months (range,11.2-58.5 months);9 without postoperative adjuvant chemotherapy had a disease-free survival time of 2.9 months (range,1.4-35.7 months),and a overall survival time of 14.5 months (range,3.0-62.3 months);there was a significant difference in the disease-free survival time between the two groups (x2 =6.687,P＜0.05),and no significant difference in the overall survival time between the two groups (x2=2.938,P＞ 0.05).Conclusions LNR can be used as a supplementation of AJCC N staging system.In patients with 0＜ LNR ≤ 0.15,postoperative adjuvant chemotherapy can improve disease-free survival time and overall survival time.
ABSTRACT
Objective:To study the effects of SiO2 nanoparticles on the organs of mice in vivo after intratracheal instillation, and to provide the basis for safety evaluation of SiO2 nanoparticles. Methods:Forty female BALB/c mice aged 6-8 weeks were randomly divided into control group (saline), low dose of SiO2 group (7 mg·kg-1), middle dose of SiO2 group (21 mg·kg-1), and high dose of SiO2 group (35 mg·kg-1).1 and 15 d after five times of non-exposed intratracheal instilation infection (once every 3 d), the mice were sacrificed and the left lungs,the right kidneys, livers, hearts and spleens were collected and embedded in paraffin.The morphology of tissue sections was observed under light microscope after hematoxylin-eosin (HE) staining.The eyeball blood was obtained and the biochemical indicators of liver and kidndy functions were detected.Results:Compared with control group, there were alveolar interval thickening, inflammatory cell infiltration, and a small amount of small arterial thrombosis in the lungs;granulomatous inflammatory cell infiltration and a small amount of focal necrosis of liver cells in the livers;red pulp enlargement, hyperemia, and more visibly scattered megakaryocytes in the spleens in SiO2 nanoparticles groups in a dose-dependent manner, especially in middle and high doses of SiO2 groups.After 15 d of injection, the damages alleviated with the prolongation of time.There was some inflammatory cell infiltration in the kidney tissue of the mice in SiO2 nanoparticle groups.The biochemical indicator detection results showed that alanine aminotransferase(ALT) and aspartate transaminase(AST) levels in SiO2 nanoparticles groups varied, suggesting the liver cell damages were at different degrees;the changes of urea nitrogen(BUN) and creatinine(Cr) levels in SiO2 nanoparticle groups remindered the kidney function alteration, but there were no obvious dose-and time-dependent effects.Conclusion:Intratracheal instillation of SiO2 nanoparticles can influence the major organs of the mice and mainly displays in the inflammation and injuries in the lung, liver, and spleen.
ABSTRACT
Objective T o explore the characteristics of schizophrenia patients' hom icide behaviors and the influences of the assessm ents of crim inal capacity. Methods Indicators such as dem ographic and clinical data, characteristics of crim inal behaviors and crim inal capacity from the suspects w hom w ere diagnosed by forensic psychiatry as schizophrenia (n=110) and norm al m ental (n=70) w ith hom icide behavior, w ere collected by self-m ade investigation form and com pared. T he influences of the assessm ents of crim inal capacity on the suspects diagnosed as schizophrenia w ere also analyzed using logistic regression analysis. Results T here w ere no significant statistical differences betw een the schizophrenic group and the norm al m ental group concerning age, gender, education and m arital status (P>0.05). T here w ere significant sta-tistical differences betw een the tw o groups concerning thought disorder, em otion state and social function before crim e (P<0.05) and there w ere significant statistical differences in som e characteristics of the case such as aggressive history (P<0.05), cue, trigger, plan, crim inal incentives, object of crim e, circum stance cognition and self-protection ( P<0 .05 ) . M ultivariate logistic regression analysis suggested that thought disorder, em otion state, social function, crim inal incentives, plan and self-protection before crim e of the schizophrenic group w ere positively correlated w ith the crim inal capacity (P<0.05). Conclusion T he rele-vant influences of psychopathology and crim e characteristics should be considered com prehensively for im proving the accuracy of the crim inal capacity evaluation on the suspects diagnosed as schizophrenia w ith hom icide behavior.
ABSTRACT
Objective:To investigate the influence of magnetic Fe3O4 nanoparticles in the expressions of Caveolin-1 and Clathrin Heavy Chain proteins in organ tissues of the rats, and to clarify its mechanism.Methods:Twenty-four Wistar rats were randomly divided into control group, and low,medium and high doses of magnetic Fe3O4 nanoparticle groups by weights.24 h after tail vein injection of different doses of magnetic Fe3O4 nanoparticles, the organ tissues were obtained.Western blotting method was used to detect the expressions of Caveolin-1 and Clathrin Heavy Chain proteins in the main organ tissues of the rats.Real-time fluorescent quantitative PCR was used to measure the expressions of Caveolin-1 and Clathrin Heavy Chain mRNA.Results:Compared with control group,the expressions levels Clathrin Heavy Chain protein and mRNA in liver and spleen tissues of the rats in medium and high doses groups were significantly increased (P0.05).Compared with control group,the Caveolin-1 mRNA expression levels in liver, spleen, and lung tissues of the rats in low,medium and high doses groups were significantly increased (P0.05).Conclusion:Magnetic Fe3O4 nanoparticles could enhance the expressions of Clathrin Heavy Chain in the liver, spleen, and lung tissues of the rats.Endocytosis of Clathrin Heavy Chain protein is one way for magnetic Fe3O4 nanoparticles into the liver, lung, spleen cells of the rats.
ABSTRACT
<p><b>OBJECTIVE</b>To analyze the relationship between primary tumor location and clinical response of chemotherapy in patients with metastatic colorectal cancer(mCRC).</p><p><b>METHODS</b>Clinical data of 721 mCRC patients who received first-line and second-line chemotherapy in Peking University Cancer Hospital between January 1996 and December 2011 were collected. All the patients were divided into 5 groups according to primary tumor location: ileocecum in 61 patients(8.5%), ascending colon or hepatic flexure in 126 patients (17.5%), transverse colon or splenic flexure in 26 patients (3.6%), descending or sigmoid colon in 172 patients (23.9%), rectum in 336 patients (46.6%). Outcomes of chemotherapy were evaluated by Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1), including complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). The overall response rate (ORR) was counted with the total number of patients divided by the number of CR+PR. Differences in first-line and second-line chemotherapy efficacy among different primary tumor sites in metastatic colorectal cancer were compared by using Chi-square test.</p><p><b>RESULTS</b>Of the 571 patients receiving first-line chemotherapy, no one patient was classified as CR, while there were 190 as PR (33.3%), 277 as SD (48.5%) and 104 as PD (18.2%), with ORR 33.3% (190/571). The ORRs of patients with primary tumor located at ileocecum, ascending colon or hepatic flexure, transverse colon or splenic flexure, descending or sigmoid colon, rectum were 21.3% (10/47), 35.3% (36/102), 14.3% (3/21), 41.3% (57/138) and 31.9% (84/263), respectively, with statistically significant difference(P = 0.028). Difference of oxaliplatin-based first-line chemotherapy efficacy among different tumor sites was statistically significant(P = 0.009), while differences in irinotecan-based or single-agent 5-fluorouracil chemotherapy efficacy were not statistically significant (all P>0.05). In patients with primary tumor located at transverse colon or splenic flexure, irinotecan-based first-line chemotherapy had higher ORR than oxaliplatin-based or single-agent 5-fluorouracil chemotherapy, and the difference was statistically significant (P=0.042). There was no significant difference in the efficacy of different first-line chemotherapy regimens in patients with primary tumor located at other sites (all P>0.05). Of the 353 patients receiving second-line chemotherapy, no one patient was classified as CR, while there were 43 as PR (12.2%), 187 as SD (53.0%) and 123 as PD (34.8%), with ORR 12.2%(43/353). The ORRs of patients with primary tumor located at the ileocecum, the ascending colon or the hepatic flexure, the transverse colon or the splenic flexure, the descending or sigmoid colon, the rectum were 4.2%(1/24), 12.1%(8/66), 8.3%(1/12), 15.2%(12/79) and 12.3%(21/171) respectively, without statistically significant difference (P=0.686). Differences in second-line chemotherapy efficacy with the same regimen among different tumor sites were not statistically significant, and there were also no significant differences of efficacy of different second-line chemotherapy regimens in patients with the same tumor site (all P>0.05).</p><p><b>CONCLUSION</b>There are differences in first-line chemotherapy efficacy among different primary tumor sites in metastatic colorectal cancer, while their second-line chemotherapy efficacy is equivalent.</p>
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Camptothecin , Colon, Sigmoid , Colon, Transverse , Colorectal Neoplasms , Drug Therapy , Fluorouracil , Therapeutic Uses , Organoplatinum Compounds , Therapeutic Uses , Rectum , Retrospective StudiesABSTRACT
A method for determination of 6 plant growth regulators by high performance liquid chromatography-tandem mass spectrometry ( HPLC-MS/MS ) coupled with isotope-coded derivatization was developed. d0-10-Methyl-acridone-2-sulfonyl piperazine ( d0-MASPz, light form) and d3-10-methyl-acridone-2-sulfonyl piperazine ( d3-MASPz, heavy form ) were prepared as isotope-coded derivatization reagents for carboxyl compound. The carboxyl plant growth regulator standards and real samples were derivatized by d0-MASPz and d3-MASPz, respectively. The obtained solutions were mixed at a certain ratio, and then injected for HPLC-MS/MS analysis. The light and heavy derivatives were monitored with transitions of [M+H]+m/z 208. 2 and [M+H]+ m/z 211. 2,respectively. With heavy derivative as internal standard for corresponding light derivative, the global isotope internal standard quantification for 6 plant growth regulators was achieved. The results indicated that the proposed isotope-coded derivatization method could provide relative quantitative data with adequate linearity in a 10-fold dynamic range ( R=0 . 9991 ) . The detection and quantitation limits were 0. 19-0. 34 μmol/L and 0. 53-0. 96 μmol/L, respectively. The relative standard deviations were ≤3 . 8%, and the accuracies ranged from 97 . 5% to 103 . 8%.
ABSTRACT
Objective To study the adjuvant immunoactivity of polysaccharides from Panax japonicus by alcohol of different concentrations;To discuss its part with the strongest adjuvant immunoactivity. Methods Polysaccharides from Panax japonicus was sunk with alcohol of different concentrations, and 30%alcohol compound, 60%and 90%alcohol polysaccharide were obtained. Different segments of polysaccharide and OVA protein were injected to mice once a week for three times for immunity. Five days after the last immunity, the mice were executed to collect blood, and the antibody titer was determined. The three parts of alcohol compound were scanned by infrared spectrum to determine the type of polysaccharide preliminarily. Results Compared with the control group, the antibody titer of different segments of polysaccharide obviously increased, especially the polysaccharide sunk by 60%alcohol. Infrared spectrum analysis showed that polysaccharides from Panax japonicus contained pyranose ring structure. Conclusion Polysaccharides from Panax japonicus has significant adjuvant immunoactivity, and polysaccharide sunk by 60%alcohol has the strongest adjuvant effects.
ABSTRACT
Objective To explore the immunogenicity of recombinant chimeric 6Aβ15-T including the Aβ1-15 epitope and a T-helper epitope formulated with different adjuvants and to evaluate its feasibility as a candidate vaccine for Alzheimer disease (AD).Methods The recombinant chimeric antigen 6Aβ15-T formulated with Al adjuvant, Freund′s adjuvant or MF59 adjuvant was administered to two strains of mice .The 6Aβ15-T-immunized group without adjuvants ( Mock) and non-immunized group (Control) were included in this study as control groups .The specific antibody and cellular immune response of the chimeric antigen were evaluated .Results In BALB/c strain mice, three types of adjuvants could substan-tially boost the immunogenicity of chimeric antigen 6Aβ15-T and produce a high level of specific-Aβ(β-amyloid) antibod-ies.In C57BL/6 strain mice, the existence of adjuvants enhanced the immune response of 6Aβ15-T antigen, but the mice in Mock group also produced a strong antibody response .In two strains of mice, prevalence of anti-AβIgG1, which was an indicator of Th2 polarization, was observed in the 6Aβ15-T-immunized mice.Additionally, the Al adjuvant induced a high-er level of IgG1 antibody titers, and the ratio of IgG1/IgG2a was the largest.As expected, the 6Aβ15-T antigen formulated with or without adjuvants induced PADRE-specific, but not Aβ42-specific T cellular immune response .Conclusion The 6Aβ15-T antigens formulated with different types of adjuvants could induce strong Th 2-polarized Aβ42-specific antibody re-sponses without activating self-reactive Aβ42-specific T cells in two strains of mice .The results suggested that the recombi-nant chimeric antigen 6Aβ15-T is a good candidate vaccine for AD .
ABSTRACT
Objective To establish mouse poisoning model by inhaling benzene, and to investigate the induction effect of benzene on the apoptosis of mouse bone marrow cells and its mechanism, and to provide an experimental basis for study on bone marrow toxicity mechanism.Methods 24 male mice were randomly divided into four groups (n=6).The mice in one group were exposed to ambient air (control group)and the mice in the other three groups were exposed to different doses (400,800,1 600 mg·m-3 )of benzene (low,middle and high doses of benzene groups)for 1 5 d in the respective inhalation chambers. At the end of the experiment, the mice were killed. The bone marrow of the mice was obtained. The pathological changes of the bone marrow cells of the mice in various groups were observed under light microscope with HE staining.The apoptotic rates and mitochondrial membrane potential (MMP ) of the mice in various groups were detected by flow cytometry, and the expressions of mitochondrial-deperdent apoptosis related gene proteins were determined with immunohistochemistry method. Results The number of distal and central cells in different doses of benzene groups were significantly reduced,and accompanied by blood sinus expansion in high dose of benzene group.The apoptotic rates of the cells in middle and high doses of benzene groups were obviously higher than that in control group (Ρ<0.01),and there were also significant differences between high dose group and low,middle doses of benzene groups (Ρ<0.05).The MMP was significantly decreased with the increasing of benzene doses, and there were significant differences between middle,high doses of benzene groups and control group (Ρ<0.05).The number of Bax,CytC positive cells in different doses of benzene groups and the number of Caspase-9,Caspase-3 positive cells in middle and high doses of benzene groups were significantly increased compared with control group(Ρ<0.05);the number of Bcl-2 positive cells in different doses of benzene groups was decreased(Ρ<0.05),and number of Bcl-2 positive cells in middle and high doses of benzene groups was decreased compared with low dose of benzene group (P<0.05). Conclusion Benzene with certain dose can induce the apoptosis of mouse bone marrow cells, and promote the expressions of mitochondrial apoptosis related gene proteins. Benzene-induced apoptosis through mitochondrial-dependent apoptosis pathway may be an important mechanism of bone marrow toxicity induced by benzene.
ABSTRACT
Objective To investigate the cytotoxicity of silica nanoparticles on vascular endothelial cells, and to clarify its action mechanism.Methods The 60 nm silica nanoparticle was selected and the invitro cultured human umbilical vein endothelial cells (HUVECs)were used as cell model.The HUVECs were divided into control and silica nanoparticle exposure groups with concentrations of 12.5,25.0,and 100.00 mg·L-1 .MTT assay was used for the determination of cell viability,lactate dehydrogenase (LDH)release assay for membrane integrity,flow cytometry (FCM)for intracellular reactive oxygen species (ROS)content,and real-time PCR assay for intracellular NF-E2-related factor 2 (Nrf2 ), heme oxygenase-1 (HO-1 ), superoxide dismutase 2 (SOD2 ) and glutamate-cysteine ligase catalytic subunit (GCLC)mRNA levels.Results The MTT results showed that the cell viabilities in each silica nnaoparticle exposure group were decreased compared with control group in a dose-dependent manner. Upon the silica nanoparticle exposure for 12 h,the cell viability was declined significantly only in 100 mg·L-1 exposure group compared with control group (P<0.05).When exposured for 24 h,the cell viabilities in 25.0, 50.0,and 100.0 mg·L-1 exposure groups were declined significantly compared with control group (P<0.05). Under the exposure to silica nanoparticle with the same dose, the cell viabilities were decreased along with the elongation of exposure time.LDH assay and FCM showed that except for that in 12.5 mg·L-1 exposure group, both the LDH activities in media and intracellular ROS levels in other exposure groups were increased compared with control group (P<0.05 ). The results of real-time fluorescence PCR showed that the mRNA levels of Nrf2, HO-1,SOD2 and GCLC in 100 mg·L-1 silica nanoparticle exposure group were increased significantly compared with control group (P<0.05).Conclusion Silica nanoparticles have toxicity to vascular endothelial cells,which includes reducing cell viability,membrane integrity destruction,induction of ROS generation,and tranSCriptional regulation of redox-related factors. Oxidative damage is one of the mechanisms of vascular endothelial toxicity mediated by silica nanoparticles.
ABSTRACT
Objective To establish a high throughput screening assay for identifying human small molecular antagonists targeted IL-6R.Methods The full length gene of the human IL-6R extracellular region was amplified by PCR and cloned into a eukaryotic expression vector to construct recombination expression plasmid pABHis -IL6R that was then transfected transiently into HEK293T cells to prepare recombination protein IL-6R.Western blotting assay and receptor-ligand binding experiment were used to analyze the bioactivity of IL-6R.A new screening method based on ELISA was established using the function of IL-6R binding to its ligand and the characteristics of Fc fragment binding to IgG-HRP.Then Z′-factor was calculated and a known antagonist ab 47215 was used to assess the stability and reliability of the new assay .Results Recombination plasmid pABHis-IL6R was constructed and soluble IL-6R was prepared.IL-6R reported herein could be recognized by an anti-IL-6R antibody and specifically bind to its ligand in a dose response manner .A Z′-factor of 0.53 was obtained that could serve high throughput screening assay .Ab47215 , as a known specific antagonist , was able to block rhIL-6 from binding to the receptor in a dose-dependent manner in the new screening assay , the IC50 of which was (0.55 ± 0.11)μg/ml.Conclusion An innovative and easy screening assay for identifying human IL-6R antagonists is established , which might help discover potent and specific antagonists .
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the mechanism of genetic toxicity of gaseous benzene to mouse bone marrow cells and to provide an experimental basis for the discovery of early biomarkers among benzene-exposed population.</p><p><b>METHODS</b>Male mice were randomly divided into control group and three benzene-exposed groups (6 mice per group). The control group was exposed to ambient air, and the three benzene-exposed groups were exposed to different concentrations of benzene (400, 800, and 1 600 mg/m(3)) for 15 days, 2 hours per day, in static inhalation chambers. At the end of the 15-day experimental period, the mice were killed. Bone marrow cells were separated from sacrificed mice, and superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-Px) activity, myeloperoxidase (MPO) activity, and malondialdehyde (MDA) content were determined by biochemical methods. DNA damage was evaluated by micronucleus assay and single cell gel electrophoresis (SCGE). The expression of MPO protein was determined by immunocytochemistry.</p><p><b>RESULTS</b>The SOD activities in different dose groups (88.67 ± 13.58, 73.64 ± 4.50, and 67.63 ± 5.42 U/mg prot) were significantly decreased as compared with the control group (119.98±9.42 U/mg prot) (P<0.01). Moreover, the SOD activities in medium- and high-dose groups were significantly lower than that of the low-dose group (P < 0.05). The GSH-Px activities in medium- and high-dose groups (705.07 ± 93.75 and 674.77 ± 86.80 U/mg prot) were significantly decreased as compared with that of the control group (940.25 ± 82.63 U/mg prot) (P < 0.01), and the high-dose group had a significantly lower GSH-Px activity than the low-dose group (674.77 ± 86.80 U/mg prot vs 833.98 ± 130.64 U/mg prot, P < 0.05). The MDA content of low-, medium-, and high-dose groups (22.42±2.67, 22.38±3.02, and 27.66±2.89 nmol/mg prot) were significantly higher than that of the control group (12.35±1.58 nmol/mg prot) (P < 0.01), and MDA content was significantly higher in the high-dose group than in the medium- and low-dose groups (P < 0.05). The micronucleus assay showed that the micronucleus rates in different dose groups (4.67±0.82‰, 5.00±0.89‰, and 5.33±1.03‰) were significantly higher than that of the control group (2.50±0.55‰) (P < 0.01). The SCGE demonstrated that the DNA damage rates of medium- and high-dose groups (22.08% and 25.68%) were significantly higher than that of the control group (7.00%) (P < 0.01), and the DNA damage rate of high-dose group was significantly higher than that of the low-dose group (11.24%) (P < 0.05). MPO activity increased with the dose of benzene in all three benzene-treated groups (16.79±2.16, 19.46±2.28, and 22.53±2.76 U/g prot) and was significantly higher than that of the control group (12.89±0.74 U/g prot) (P < 0.01). The positive rates of MPO protein expression in low-, medium-, and high-dose groups (13.20±2.28%, 30.80±3.35%, and 40.20±1.92%) were significantly higher than that of the control group (6.60±1.14%) (P < 0.01). The MPO activity in high-dose group and the positive rates of MPO protein expression in medium- and high-dose groups were all significantly higher than those of the low-dose group (P < 0.01).</p><p><b>CONCLUSION</b>Gaseous benzene exposure has toxic effect on genetics of mouse bone marrow cells. It leads to chromosome breakage and DNA damage, enhances the activity and protein expression of MPO, and induces lipid peroxidation. Lipid peroxidation damage is a potential mechanism by which gaseous benzene exerts toxic effect on mouse bone marrow cells.</p>
Subject(s)
Animals , Male , Mice , Apoptosis , Benzene , Toxicity , Bone Marrow Cells , Metabolism , Pathology , DNA Damage , Lipid PeroxidationABSTRACT
Objective:To identify the ABCG2 expression levels in colorectal cancer patients and its relationship with clinicopath-ological features and the efficacy of irinotecan-based chemotherapy and to provide further theoretical basis for individualized treatment. Methods:Clinical data and tumor samples from patients with metastatic CRC who have received irinotecan-based chemotherapy at the Department of Gastroenterological Oncology, Peking University Cancer Hospital from January 1996 to December 2011 were collected. The immunohistochemical method was used to detect ABCG2 expression levels both in colorectal carcinoma and tumor-adjacent nor-mal tissues. The correlations of the expression of ABCG2 with clinicopathological features and the efficacy of irinotecan-based chemo-therapy were statistically analyzed. Results:1) Immunohistochemical staining shows that the positive rate of ABCG2 expression in the colorectal cancer samples is 93.2%, which is significantly higher than that in normal colon mucosa at 43.6%(P0.05). Conclusion:ABCG2 expression has no significant correlation with the efficacy of irinotecan chemotherapy in patients with colorectal cancer.
ABSTRACT
Objective To compare the toxicity and anti-inflammatory effect of total saponins from Panax japonicus by different extraction technology. Methods The total saponins of sample 1, sample 2, sample 3, sample 4, sample 5 and sample 6 was prepared respectively by different process, and RAW264.7 cells were treated with the samples of different concentration. Then cells morphology was observed under microscope, thiazolyl blue (MTT) method was used to detect cell activity, the nitric oxide (NO) release of RAW264.7 cells was detected with NO kit. Results The cell toxicity of different samples from low to high was as follows:sample 4sample 5>sample 2>sample 6>sample 1>sample 3. Conclusion Among these six different kinds of extraction process of total saponins from Panax japonicus, the total saponins extract by foam fractionation has not only the minimal toxicity, but also the best primary anti-inflammatory effect.
ABSTRACT
Objective To look for a reliable and convenient judgement criteria for the screening of cytomegalovirus pneumonia in order to reduce misdiagnosis and resulted mistherapy.Methods Process collected data on fifty-six cytomegalovirus pneumonia and forty-two common viruses induced asthmatic bronchitis cases by use of discriminant analysis to construct prediction model of diagnosis result.Results Only three indexes including age,lymph count and platelet count were selected into the model via sift.The performance of the established screening model showed as follows:sensitivity was 80.36％,specificity was 80.95％,misdiagnosis rate was 19.05％,false negative rate was 19.64％,diagnostic accordance rate was 80.61％.Conclusion Being concise and of strong maneuverability and high accuracy in prediction,cytomegalovirus pneumonia diagnosis model constructed through discriminant analysis can provide powerful screening means for medical staff.
ABSTRACT
Objective To explore a new technique to treat the benign stricture at hilar bile duct of plastic anastomosis, so as to obtain the theoretical basis and the feasibilities of practical application in treating the benign stricture at hilar bile duct with plastic anastomosis through the animal experiments. Methods 30 miniature pigs were randomly divided into three groups. Group A (control group):2 centimeters of the bile duct above the duodenum was isolated;Group B:The same separation of bile duct with group A, then making physical injury on it with the clamps and electric heat;Group C:Making bile duct injury model in group C as group B,and then monitoring of the diet, feces, urine, ALT, AST and bilirubin etc. When the bile duct stricture was formed, taking the plastic anastomosis operation in this group. After all the operations, we observed the diet, mental state and the color of the urine of animals in all the three groups, and tested ALT,AST,T-BIL and D-BIL levels on the pre- and post-day and every 7 days after surgery respectively. After three months of the surgery,we executed all the pigs,picked up part of the liver tissue,then preserved them by liquid nitrogen for pathological examination. Results From the day before operative-day to the 30 days after operation, there was no significant change in ALT, AST, T-BIL and D-BIL in group A,while the relative indicators of group B and C had obvious changes ( <0.05) . The indicators of group B were significantly increased 21 days after surgery, compared with pre-operation and 14 days after operation respectively ( <0.05) . In group C, the indicators were significantly declined 14 to 21 days after the plastic anastomosis compared with pre-operation (<0.05) . Conclusions Treating benign stricture at hilar bile duct of miniature pigs by plastic anastomosis is feasible and practicable. This study provides an experimental basis for clinical application of plastic anastomosis in treatment of benign stricture at hilar bile duct.
ABSTRACT
Objective To investigate the differences in the safety of the operation of different hepatic vascular exclusion for liver surgery. Methods Sixty patients with liver resection were grouped by different hepatic blood flow blocking methods, and given pre-operative assessment prior to surgery. Results On the first day after surgery, the average levels of ALT and AST were (395.0 ± 220.2) U/L and (415.3±311.0) U/L in patients who received Pringle’s method (110.2±53.0) U/L and (125.6±78.5) U/L in patients who received regional hepatic vascular exclusion, (98.9±32.2) U/L and (96.2 ±66.5) U/L in patients who didn't receive hepatic vascular exclusion, respectively. Postoperative liver function damage was more serious in patients who received Pringle's method than patients who received regional hepatic vascular exclusion or patients who didn't receive hepatic vascular exclusion, the difference was statistically significant (P<0.05) .Conclusion Regional hepatic vascular exclusion or not can not only reduce the incidence of postoperative complications, but also expand the indications for liver resection.