1.Immune intervention of human umbilical cord mesenchymal stem cells on sepsis rats
Hewei ZHANG ; Xiaoxu CUI ; Tao FANG ; Qiang FU
Chinese Critical Care Medicine 2017;29(8):705-710
Objective To investigate the effect of human umbilical cord mesenchymal stem cells (UC-MSCs) on immune cells and inflammatory factors in septic rats.Methods 184 male Sprague-Dawley (SD) rats were divided into normal control group (n = 8), sham operation group (n = 48), sepsis model group (n = 64), and UC-MSCs treatment group (n = 64). An animal model of sepsis was produced by cecal ligation and puncture (CLP). In the UC-MSCs treatment group 1 mL UC-MSCs (2×106/mL) were injected intraperitoneally at 1 hour after the model establishment;the sham operation group and the sepsis model group were given the same amount of saline. Sixteen animals in each group of the sham operation group, sepsis model group, and UC-MSCs treatment group were observed for 72-hour survival rate. The percentages of CD4+ T cells and the ratio of helper T cells 1/2 (Th1/Th2) in whole blood cells were measured by flow cytometry at 12, 24, 48 and 72 hours after operation. The levels of tumor necrosis factor-α (TNF-α), high mobility group box 1 (HMGB1), interleukin-10 (IL-10) were measured by enzyme linked immunoabsorbent assay (ELISA).Results The 72-hour survival rate of the UC-MSCs treatment group was slightly higher than that of the sepsis model group [62.5% (10/16) vs. 50.0% (8/16),χ2 = 0.509,P > 0.05]. The percentage of CD4+ T cells and Th1/Th2 ratio in the sepsis model group were significantly higher than those in the sham operation group at 12 hours after operation, and decreased as the time prolonged to 48 hours. The levels of plasma inflammatory factors were significantly higher than those of sham operation group at 12 hours after operation, TNF-α and IL-10 were decreased at 48 hours after operation, while HMGB1 continued to increase until 72 hours after operation. Compared with those in the sepsis model group, the percentages of CD4+ T cells at 12 hours and 24 hours after operation [(49.66±0.91)% vs. (59.11±1.17)%, (41.80±0.89)% vs. (49.84±0.99)%], the levels of Th1/Th2 ratio at 12, 24, 48 hours after operation (0.745±0.065 vs. 1.254±0.115, 0.407±0.077 vs. 0.806±0.061, 0.280±0.057 vs. 0.454±0.049), and the levels of TNF-α and HMGB1 were significantly reduced at 12, 24, 48 and 72 hours after operation in the UC-MSCs treatment group [TNF-α(ng/L):52.60±6.60 vs. 58.03±6.53, 71.77±8.48 vs. 147.39±11.37, 111.83±10.76 vs. 271.36±19.04, 83.09±7.43 vs. 171.04±14.06; HMGB1 (ng/L): 149.12±9.89 vs. 187.33±12.79, 192.94±14.92 vs. 442.35±52.72, 1393.67±88.86 vs. 1950.90±126.66, 1875.84±111.67 vs. 2557.12±186.01], all with statistically significant differences (allP <0.05). The level of IL-10 was significantly higher at 12, 24, 48 and 72 hours after operation (ng/L: 65.46±5.51 vs. 33.32±4.17, 86.49±5.78 vs. 63.11±5.53, 142.73±9.94 vs. 106.81±6.36, 123.74±10.90 vs. 89.90±7.71, allP <0.01).Conclusion UC-MSCs can make CD4+ T cells in early sepsis, and Th1/Th2 ratio to normal, by reducing the levels of proinflammatory factors, and increasing the level of anti-inflammatory factor, and improve sepsis immune function status, but cannot improve the survival rate of animals.
2.The study on apoptosis induced by disodium cantharidinate and vitamin B6 in glioblastoma cells U87
Xiangli CUI ; Xiaoxu SHI ; Yan WANG ; Yajie WANG ; Haowen LI ; Li LIU ; Yuan REN ; Zhigang ZHAO
Practical Oncology Journal 2014;(2):129-134
Objective The purpose of this study is to investigate the apoptosis mechanisms of glioblasto-ma cell line U87 induced by sodium cantharidinate ( SCA) in vitro.Methods Growth inhibition of U87 by 0.625μg/mL,1.25μg/mL,2.5μg/mL,5μg/mL SCA at 24 h,48 h,72 h were analyzed by MTT assay respec-tively.Morphological changes of U 87 nuclear were detected by fluorescence microscope .U87 cell apoptosis and cell cycle arrest were detected after SCA treatment for 24 h and 48 h by flow cytometry.The changes of apoptosis-related genes Bcl -2,Bax,Caspase-3 expression were analyzed after 24 h of SCA treatment by RT -PCR as-say.Results MTT assay showed that growth inhibition of U 87 cell induced by SCA was accompanied with the in-creased drug concentration ,Hoechst33258 staining showed the morphology of apoptotic U 87 cells nucleui ,chromo-some condensation ,nuclear condensation ,some nuclear fragmentation and formation of apoptotic bodies .Flow cy-tometry showed that SCA could induce cell cycle arrest at the G 2/M phase,and could induce apoptosis of U87.RT-PCR results showed that after 24 h of SCA treatment caspase -3,bax expression of U87 was significantly higher than the control group(P<0.05),bcl-2 expression was significantly decreased (P<0.05),and P53 expression was not significantly increased(P>0.05).Conclusion Our results demonstrate that SCA can inhibit U87 pro-liferation and induce apoptosis of U 87 .
3.A comparative study of two hyperthyroidism models induced by Yersiniaenterocolitica and Euthyrox
Shumin LIU ; Xiaoxu CUI ; Pingping CHEN ; Kexin WANG ; Na WANG ; Changfeng LIU
Chinese Journal of Comparative Medicine 2014;(7):19-24
Objective To provide a good evaluation for research the hyperthyroidism drugs , two kinds of hyperthyroidism animal models were copied , and compared the similarities and differences of their formability and sustainability.Methods Euthyrox-induced model: The rat was taken Euthyrox (50μg· 100g-1 rat weight) for 21 d. And then the blood and urine were collected in 1 d, 7 d and 14 d after last time oral administration of Euthyrox;Yersiniaenterocolitica-induced model:the rats were injected Yersiniaenterocolitica (YE) in 0、5、10、15、20 (IOCV).And then the blood and urine were collected in 5d, 15d and 25d after last IOCV of YE.Results Euthyrox-induced model:T3, T4, FT3, FT4 were increased significantly , but returned normal 1 week later in the model group , PCA showed that model group deviated from the blank group , but recovered 2 weeks later; Yersiniaenterocolitica-induced model: T3 and T4 were increased significantly in 15 and 25 d, TSH significant raised in 25 d, the model group deviated from the blank group in PCA, and didn’t return to the blank group in 15d or 25d.Conclusion Euthyrox-induced modelhas good formability butrecovered quickly , which is suitable for prevention of drug delivery on efficacy evaluation; Yersiniaenterocolitica-induced model with good formability and sustainability could be used for treatment of drug delivery on efficacy evaluation .
4.Study on the relationship between the expression of TLR7/8 in monocytes and the disease progression of HIV-1 infection
Hua NIAN ; Wenqing GENG ; Hualu CUI ; Zining ZHANG ; Min ZHANG ; Xiaoxu HAN ; Bin ZHAO ; Qinghai HU ; Hong SHANG
Chinese Journal of Microbiology and Immunology 2009;29(11):992-996
Objective To examine the expression of TLR7/8 in monocytes purified from HIV-1 infected individuals and to study its association with disease progression. Methods Sixty-three HIV-1 infected individuals and 18 normal controls were enrolled. Monocytes were purified by MACS system and RNA of them was extracted by RNA mini kit of QIAGEN company. TLR7/8 expression was tested by real-time RT-PCR with ABI7500. Results It was found that the expression of TLR7 was strongly correlated with absolute CD4 count (r =0.614, P<0.01) , so was TLR8 (r =0.419, P<0.01). The expression of TLR7 in slow progressor (SP) group was higher than that in HIV-1 infected patients group, AIDS patients group and normal group (P < 0. 05 ) . HIV group and normal group were strongly higher than AIDS group (P < 0. 05). It was no significant differentiation of expression of TLR7 between HIV infection group and normal control group. The expression of TLR8 in SP group and normal group were significantly higher than that in AIDS group (P < 0. 05). The expression of TLR8 was no singnificantly difference between SP group and HIV group or normal control group, so was it between HIV group or normal control group and AIDS group. Conclusion The expression of TLR7/8 in monocytes from HIV-1 infected patients significantly correlated with disease progression.
5.Study on the relationships between neutralizing antibody response against heterologous virus and disease progression of HIV type 1 B'/C infected individuals in China
Mingjia BAO ; Wenqing GENG ; Hualu CUI ; Xiaoli ZHANG ; Dongbing XU ; Yating WANG ; Ying PAN ; Yongjun JIANG ; Yanan WANG ; Xiaoxu HAN ; Min ZHANG ; Zining ZHANG ; Hong SHANG
Chinese Journal of Microbiology and Immunology 2009;29(2):165-169
Objective To study the relationships between neutralizing antibody response against heterologous virus and disease progression in Chinese HIV-1 B'/C infected individuals. Methods Plasmas from HIV-1-infected individuals, grouped as HIV chronically infected or AIDS according to CD4+ count and clinical symptom, were tested for neutralizing activity against the three HIV-1 isolates with very low homology in vitro. Six two-fold dilutions of each plasma sample (from 1/10 to 1/320) were tested against each virus from the panel. Giving a 50% reduction in p24Ag compared with normal human plasma control wells was defined as positive. The breadth of the cross-neutralizing response was defined based on the number of viruses that were effectively neutralized by any given patient-derived plasma sample. The magnitude of the crossneutralizing response was defined based on the average neutralizing titer against all heterologous viruses. Resuits We found that there revealed a significant difference between HIV chronically infected and AIDS group in the breaths and magnitudes of neutralizing heterologous virus. There was higher prevalence for the frequency of neutralizing heterologous virus in HIV chronically infected than AIDS. The results showed that there was positive correlation between the breadths and magnitudes of neutralizing response against heterologous virus and the plasma HIV RNA level in HIV chronically infected group, while not in AIDS group. There was no association between the breadth of the neutralizing responses against heterologous virus and CD4 T cell counts. Conclusion The capacity of neutralizing antibodies against heterologous virus varied among different disease stage. There were higher titers of neutralizing antibodies in HIV chronically infected than AIDS group. The loss of neutralizing antibodies in plasma from AIDS group appears to be associated with a narrowing of the antibody response during disease progression. These suggest that the presence of neutralizing antibodies against hetreologous virus was associated with disease progression.
6.B lymphocyte counts and Toil-like receptor 9 mRNA expression on cell from HIV-1 infected patients
Hong SUN ; Wenqing GENG ; Hualu CUI ; Min ZHAO ; Xiaoxu HAN ; Zining ZHANG ; Jing LIU ; Di DAI ; Yanan WANG ; Yongjun JIANG ; Hong SHANG
Chinese Journal of Microbiology and Immunology 2010;30(9):860-863
Objective To study the B lymphocytes counts and the expression of TLR9 mRNA on B lymphocytes in peripheral blood from Chinese HIV-infected patients.Methods The cells from peripheral blood were stained with antibodies labeled with fluorescence and B lymphocytes were counted with flow cytometry.Using the method of magnetic activated cell sorting and real-time PCR,the expression of TLR9 mRNA was measured.Results The B lymphocytes counts in HIV/AIDS patients was significantly lower than that of healthy controls(P <0.01).The B lymphocytes counts in HIV/AIDS patients positively correlated with the CD4 +T cells counts(r =0.534,P = 0.006).The expression of TLR9 mRNA on B lymphocytes in HIV/AIDS patients was significantly lower than that of healthy controls(P =0.023),and positively correlated with the CD4 + T cells counts(r = 0.390,P = 0.040).Conclusion The B lymphocytes counts and the expression of TLR9 mRNA on B lymphocytes in Chinese HIV/AIDS patients were decreased due to HIV infection,which may correlate with disease progression.
7.Study on the relationships between neutralizing antibody response and disease progression of HIV type 1 B'/C infected individuals in China
Mingjia BAO ; Wenqing GENG ; Hualu CUI ; Xiaoli ZHANG ; Dongbing XU ; Hua NIAN ; Min ZHAO ; Yating WANG ; Yongjun JIANG ; Yanan WANG ; Xiaoxu HAN ; Min ZHANG ; Zining ZHANG ; Hong SHANG
Chinese Journal of Immunology 1985;0(06):-
Objective:To study the relationships between neutralizing antibody response against autologous virus and disease progression of HIV-1 B'/C infected individuals in China.Methods:Twenty-four primary HIV-1 isolates were incubated with autologous plasma collected either freshly or at approximately six months intervals thereafter.Normal human peripheral blood mononuclear cells were incubated with the virus-serum mixtures for 7 days and then the production of p24 antigen was measured.The neutralizing titer of a particular plasma and virus was defined as the reciprocal of the highest dilution giving a 50% reduction in p24 Ag compared with NHP control wells.More than 1∶8 were considered significant and were scored as positive.Results:In neutralizing antibody(Nabs) response against contemporaneous virus,Nabs were produced in all slow progressors(SP) individuals,while only four in 21 of HIV group had.There was statistically significance of the neutralizing antibody titers between SP and HIV.When plasma samples of six months later were tested for their ability to neutralize autologous virus,all of SPs had higher neutralizing antibody titers and the titers of neutralizing antibody in HIV group had increased in different rate.Among the twenty-one individuals of HIV group,12 of these individuals had neutralizing antibody response against autologous virus and other 9 of these individuals had not.NAb titers of SP in six months later plasma were higher than those of HIV.There was a negative correlation between the generation of the neutralizing titer against autologous virus and the plasma HIV RNA level in HIV-1 B'/C infected individuals(including SP,HIV).Conclusion:Neutralizing antibody against autologous viruses in HIV-1 B'/C infected SP is higher than those of HIV group,suggesting that neutralizing antibodies play a vital role in delaying disease progression in these individuals.
8.Multiple mediating effects of social participation and social support on the physical and mental health of the community-dwelling elderly
Qinyi DU ; Xuan MA ; Xiaoxu WANG ; Yan REN ; Xiaohong CUI ; Mei FENG
Chinese Journal of General Practitioners 2023;22(8):818-825
Objective:To investigate the status and influencing factors of activities of daily living (ADL), anxiety and depression of the community-dwelling elderly, and to explore the mediating effect of social support and social participation on ADL, anxiety and depression.Methods:A questionnaire survey was conducted from July to October 2022, among 637 residents over 60 years old registered in the Community Health Service Center of Taiyuan Economic and Technological Development Zone selected by simple random sampling method. The general information questionnaire, Activities of Daily Living (ADL) scale, Anxiety Self-assessment Scale, Depression Self-assessment Scale, Social Support Scale, and Social Participation Scale were used in the survey. The dichotomous logistic regression model was used to analyze the influencing factors of disability, anxiety, and depression of the elderly. Structural equation modeling was used to verify the mediating effects of social participation and social support on the ADL and mental health status in the elderly.Results:The disability rate of the elderly in the community was 42.9%(258/602). Age( OR=2.87-4.91), acute disease attack in the last three months( OR=2.03),poor economic status( OR=2.39), impaired social participation ability( OR=4.07, 11.75) and low level of social support( OR=2.37) were risk factors for disability of the elderly in the community. The incidence of anxiety symptoms was 22.7%(137/602). The risk factors of anxiety were having more than one chronic disease ( OR=2.24), poor economic status ( OR=2.27), mild and intermediate impairment of social participation ability( OR=6.97, 180.43)and low level of social support( OR=2.04). The incidence of depressive symptoms was 19.4%(117/602). The risk factors of depression were acute disease attack in the past three months ( OR=1.90), loneliness in the past three months ( OR=2.17), impaired social participation ( OR=4.17) and low level of social support ( OR=3.90). The direct effect of ADL on mental health was 0.204 (Bootstrap 95% CI:0.081-0.330), accounting for 34.58% of the total effect. The mediating effects of social participation and social support on ADL and mental health were 0.343 (Bootstrap 95% CI:0.274-0.418) and 0.042 (Bootstrap 95% CI:0.015-0.075) respectively, accounting for 58.13% and 7.12% of the total effect. Conclusions:Social support and social participation are not only the common influencing factors of ADL, anxiety and depression of the community-dwelling elderly, but also have a mediating effect on ADL and mental health. Promoting the social participation of the community-dwelling elderly and increasing social support can improve both ADL and mental health for them.
9.Serum Presepsin in the diagnosis and assessment of sepsis in children
Shuang LIU ; Yi HUI ; Ning LI ; Xiaoxu REN ; Xiaodai CUI ; Dong QU
Chinese Pediatric Emergency Medicine 2021;28(12):1082-1088
Objective:To investigate clinical significance of Presepsin(soluble CD14 subtype) in the diagnosis and condition assessment of sepsis in children compared with traditional biomarkers.Methods:For the prospective study, 102 children with sepsis admitted to the PICU of the Children′s Hospital of the Capital Institute of Pediatrics from January 2017 to December 2018 were selected, including 57 cases in the sepsis group, 45 cases in the severe sepsis/septic shock group and 25 cases in the non-infectious systemic inflammatory response syndrome(SIRS group), and 35 children with healthy physical examination during the same period as the control group.The sepsis group was further divided into the survival group( n=86)and the death group( n=16)based on the 28-day mortality.The data collected included serum Presepsin, procalcitonin(PCT), C-reaction protein(CRP) and interleukin(IL)-6 levels on days 1, 3 and 7 of admission, and compared with paediatric critical case scores. Results:(1)The levels of serum Presepsin [12.43(7.21, 15.07) ng/mL], PCT [23.00(5.70, 87.00) ng/mL], CRP [160.0(105.5, 200.0) mg/L], IL-6 [1 000.0(125.0, 1, 000.0) pg/mL] were significantly higher than those in the sepsis, SIRS and control groups( P<0.001). (2) The area under the ROC curve(AUC) values for Presepsin, PCT, and IL-6 subjects on day 1 of admission were 0.856, 0.812, and 0.516, respectively.The sensitivity of Presepsin at a cut-off value of 4.40 ng/mL for the diagnosis of sepsis was 81.1% and the specificity was 72.3%, which would significantly higher diagnostic efficacy of the combination of Presepsin, PCT and IL-6.(3) There was a significant difference between the survival and death groups in Presepsin( P<0.001), and Presepsin was significantly higher in the death group on days 3 and 7 than those in the survival group(both P<0.001); IL-6 was significantly higher in the death group on day 3 than that in the survival group( P=0.04); the differences in PCT and CRP between the death and survival groups at all time points were not statistically significant(both P>0.05 ). (4) The AUCs of inflammatory factors on days 1, 3 and 7 to predict sepsis outcome were 0.597, 0.656 and 0.951 for Presepsin, 0.576, 0.613 and 0.655 for PCT and 0.726, 0.786 and 0.664 for IL-6, respectively.The diagnostic values of Presepsin on day 7 and IL-6 on days 1 and 3 were higher.The combination of Presepsin, PCT and IL-6 significantly improved the prognostic judgment of sepsis.(5) The difference between sepsis-related acute kidney injury(AKI) and non-AKI was not statistically significant when comparing Presepsin on day 1 and 3(all P>0.05). Presepsin levels on day 7 were significantly higher in children with sepsis-associated AKI than in those without AKI( P<0.001). Conclusion:Presepsin is a good biomarker for sepsis diagnosis in children, which is equivalent to PCT in the diagnosis of sepsis, superior to IL-6 and superior to PCT in the prognosis evaluation.Combined testing of Presepsin, PCT and IL-6 may improve the diagnosis of sepsis and the assessment of the condition in children.
10.Treatment efficacy of DC-CIK with different loading combined with 5-FU on nude mice bearing colon cancer HT-29 cell transplanted tumor
GUO Hulin ; CUI Xiaoxu ; FENG Qingqing ; SHI Shanshan ; YAO Wenteng ; Si Yuling
Chinese Journal of Cancer Biotherapy 2019;26(12):1318-1323
Objective: To investigate the therapeutic effect of dendritic cell-induced killer cells (DC-CIK) combined with 5-fluorouracil (5-FU) and loaded with CD133+ HT-29 cell lysate or RNA on mice bearing colon cancer HT-29 cell transplanted tumor, and to explore the underlying mechanism. Methods: Colon cancer xenograft model was established in BALB /c nude mice by using human colon cancer HT-29 cells at logarithmic growth phase; Antigen-free DC-CIK, 5-FU+DC-CIK, R+DC-CIK (loaded with total RNA of CD133+ cells), L+DC-CIK (loaded with CD133+ cell lysate), 5-FU and normal saline were respectively injected into transplanted mice, and the treatment efficacies on the growth of transplanted tumor in each group after three treatment cycles were observed, and the tumor growth curve was drawn. The nude mice were sacrificed by cervical dislocation and the tumor volume and body weight were measured. qPCR was used to detect the expression of AKT mRNA in transplanted tumor tissue, and WB was used to detect the expression of phosphorylated AKT protein. Results: After treatment, the body mass of nude mice in R+DC-CIK group, L+DC-CIK group and 5-FU+DC-CIK group increased steadily, while the body mass of nude mice in DC-CIK group and 5-FU group decreased gradually; the tumor growth speed of nude mice in R+DC-CIK group, 5-FU+DC-CIK group and L+DC-CIK group was significantly slower than that of the control group (P<0.05). Compared with 5-FU and DC-CIK alone, the combined treatment with loaded lysate/RNA had more sig
nificant effect on mRNA and protein expressions of AKT(P<0.05). Conclusion: The effect of DC-CIKwithdifferentloadingoritscombinationwith5-FUisbetterthanthatofchemotherapy alone. One of the mechanisms is related to the down-regulation ofAKT level.