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Objective: To clarify the mechanisms involvement in Alisertib-resistant colorectal cells and explore a potential target to overcome Alisertib-resistance. Methods: Drug-resistant colon cancer cell line (named as HCT-8-7T cells) was established and transplanted into immunodeficient mice. The metastasis in vivo were observed. Proliferation and migration of HCT-8-7T cells and their parental cells were assessed by colony formation and Transwell assay, respectively. Glycolytic capacity and glutamine metabolism of cells were analyzed by metabolism assays. The protein and mRNA levels of critical factors which are involved in mediating glycolysis and epithelial-mesenchymal transition (EMT) were examined by western blot and reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR), respectively. Results: In comparison with the mice transplanted with HCT-8 cells, which were survival with limited metastatic tumor cells in organs, aggressive metastases were observed in liver, lung, kidney and ovary of HCT-8-7T transplanted mice (P<0.05). The levels of ATP [(0.10±0.01) mmol/L], glycolysis [(81.77±8.21) mpH/min] and the capacity of glycolysis [(55.50±3.48) mpH/min] in HCT-8-7T cells were higher than those of HCT-8 cells [(0.04±0.01) mmol/L, (27.77±2.55) mpH/min and(14.00±1.19) mpH/min, respectively, P<0.05]. Meanwhile, the levels of p53 protein and mRNA in HCT-8-7T cells were potently decreased as compared to that in HCT-8 cells (P<0.05). However, the level of miRNA-125b (2.21±0.12) in HCT-8-7T cells was significantly elevated as compared to that in HCT-8 cells (1.00±0.00, P<0.001). In HCT-8-7T cells, forced-expression of p53 reduced the colon number (162.00±24.00) and the migration [(18.53±5.67)%] as compared with those in cells transfected with control vector [274.70±40.50 and (100.00±29.06)%, P<0.05, respectively]. Similarly, miR-125b mimic decreased the glycolysis [(25.28±9.51) mpH/min] in HCT-8-7T cells as compared with that [(54.38±12.70)mpH/min, P=0.003] in HCT-8-7T cells transfected with control. Meanwhile, in comparison with control transfected HCT-8-7T cells, miR-125b mimic also significantly led to an increase in the levels of p53 and β-catenin, in parallel with a decrease in the levels of PFK1 and HK1 in HCT-8-7T cells (P<0.05). Conclusions: Silencing of p53 by miR-125b could be one of the mechanisms that contributes to Alisertib resistance. Targeting miR-125b could be a strategy to overcome Alisertib resistance.
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Animals , Female , Mice , Humans , Azepines , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , RNA, Messenger , Tumor Suppressor Protein p53/genetics , Drug Resistance, NeoplasmABSTRACT
Objective: To examine the associations between plasma n-3 polyunsaturated fatty acids (PUFAs) in the second trimester and gestational diabetes mellitus (GDM) among Chinese pregnant women. Methods: Based on data from the Tongji-Shuangliu Birth Cohort enrolled from 2017 to 2019 in the Shuangliu Maternal and Child Health Hospital, it conducted a case-control study among 269 GDM cases who were diagnosed by 75 g oral glucose tolerance test, and 538 non-GDM controls matched at a 1∶2 ratio on maternal age and gestational weeks. The age range of the 807 women was 18-40 years. Fasting plasma n-3 PUFAs were determined by gas chromatography-mass spectrometry in the second trimester (24-28 weeks). Participants were categorized into quartiles (Q1-Q4) of plasma n-3 PUFAs based on distributions in the control group. Conditional logistic regression models were applied to estimate the associations between plasma n-3 PUFAs and GDM. Results: The median (interquartile) relative concentrations of plasma n-3 PUFA C22∶5n-3 was significantly lower in women with GDM 0.87 (0.72, 1.07) compared with women without GDM 0.94 (0.75, 1.19)(P=0.001). Plasma n-3 PUFA C22∶5n-3 was inversely associated with GDM, with an OR (95%CI) of 0.75 (0.62-0.90) for each SD increase of relative concentration. Compared with the Q1 group, the OR values and 95%CIs of Q2, Q3, and Q4 groups were 0.97 (0.62-1.51), 0.72 (0.45-1.15), and 0.54 (0.32-0.90), respectively (Ptrend<0.05). However, there were no significant associations of C18∶3n-3, C20∶5n-3, C22∶6n-3, and total n-3 PUFAs with GDM. Conclusion: Plasma n-3 PUFA C22∶5n-3 was inversely associated with GDM during the second trimester.
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Child , Female , Humans , Pregnancy , Case-Control Studies , Diabetes, Gestational , Fatty Acids, Unsaturated , Glucose Tolerance Test , Pregnancy Trimester, SecondABSTRACT
OBJECTIVES@#To investigate the incidence of preterm birth and risk factors for preterm birth.@*METHODS@#A prospective cohort study was performed for the pregnant women in early pregnancy and their spouses, who underwent prenatal examination for the first time in Hunan Provincial Maternal and Child Health Care Hospital from May 2014 to December 2016 and decided to be hospitalized for delivery. A questionnaire survey was performed to collect exposure information possibly related to preterm birth. The hospital's medical record system was used for information verification and to record the pregnancy outcome. A multivariate logistic regression analysis was used to investigate the risk factors for preterm birth.@*RESULTS@#A total of 6 764 pregnant women with complete data were included, and the incidence rate of preterm birth was 17.09%. The multivariate logistic regression analysis showed that a history of adverse pregnancy outcomes, eating areca nut before pregnancy, a history of pregnancy complications, a history of hepatitis, no folate supplementation during pregnancy, medication during pregnancy, active smoking and passive smoking during pregnancy, drinking during pregnancy, unbalanced diet during pregnancy, high-intensity physical activity during pregnancy, and natural conception after treatment of infertility or assisted conception as the way of conception were risk factors for preterm birth (@*CONCLUSIONS@#There are many risk factors for preterm birth. Special attention should be paid to the life behaviors of pregnant women during pregnancy, and health education should be strengthened for pregnant women and their spouses to develop good living habits and reduce the incidence of preterm births.
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Child , Female , Humans , Infant, Newborn , Pregnancy , Pregnancy Outcome , Premature Birth/etiology , Prospective Studies , Risk Factors , Tobacco Smoke PollutionABSTRACT
This report presents an 84 year-old patient admitted into our hospital for dizziness with a history of Hashimoto's thyroiditis,chronic gastritis and vitiligo.Physical examinations showed skin depigmentation.Laboratory tests revealed anemia,positive intrinsic factor antibodies and normal adrenal function.This patient was finally diagnosed with autoimmune polyglandular syndromes(APS) type Ⅲ B +C.Recurrent anemia was mainly attributed to malabsorption caused by autoimmune gastritis.This article reviews the common clinical manifestations of APS,in order to call for geriatricians' attention to APS.APS Ⅲ B+C should be considered if vitiligo combined with anemia occurs in elderly patients.
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Pregnancy is a critical stimulator of bone mineral resorption.We used to find the MTHFR gene polymorphisms are related with blood lead levels among pregnant women.Pregnancy-stimulated bone turnover may be associated with MTHFR gene polymorphisms too.In this article,we aimed to determine the relationship between MTHFR gene polymorphisms and bone turnover rates among the pregnant women.The participants including pregnant and non-pregnant women were selected and recruited during their routine prenatal or physical examination from July to October in 2012.A total of 1000 participants,including 250 pregnant women in the first,second,and third trimesters and 250 non-pregnant women,were enrolled in the study.Finally,after excluding 27 participants unable to provide blood samples,973 eligible participants (i.e.,234,249,and 248 pregnant women in the first,second,and third trimesters,respectively,and 242 non-pregnant women)were included in the research.The MTHFR gene 1298CC homozygote carriers were more susceptible to yield higher plasma homocysteine levels than the 1298AA/AC carriers,with standardized coefficients of 0.086 (P＜0.05) and 0.104 (P＜0.01) of all the participants and the pregnant women,respectively.The MTHFR gene 1793AA homozygote carriers more likely showed higher plasma osteocalcin levels (standardized β=0.091,P＜0.01) than the 1793GG/GA carriers among all the subjects.Plasma homocysteine levels were positively correlated with blood lead levels among the participants and the pregnant women with standardized coefficients of 0.320 (P＜0.01) and 0.179 (P＜0.01),respectively.Plasma osteocalcin levels were positively associated with blood lead levels among pregnant and non-pregnant women with standardized coefficients of 0.084 (P＜0.05) and 0.125 (P＜0.01),respectively.In conclusion,homocysteine and osteocalcin contents in plasma are associated with the MTHFR gene A1298C polymorphism and blood lead levels among pregnant women.The MTHFR gene A 1298C polymorphism-related homocysteine is a possible risk factor for increased blood lead levels among Chinese women.
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Pregnancy is a critical stimulator of bone mineral resorption.We used to find the MTHFR gene polymorphisms are related with blood lead levels among pregnant women.Pregnancy-stimulated bone turnover may be associated with MTHFR gene polymorphisms too.In this article,we aimed to determine the relationship between MTHFR gene polymorphisms and bone turnover rates among the pregnant women.The participants including pregnant and non-pregnant women were selected and recruited during their routine prenatal or physical examination from July to October in 2012.A total of 1000 participants,including 250 pregnant women in the first,second,and third trimesters and 250 non-pregnant women,were enrolled in the study.Finally,after excluding 27 participants unable to provide blood samples,973 eligible participants (i.e.,234,249,and 248 pregnant women in the first,second,and third trimesters,respectively,and 242 non-pregnant women)were included in the research.The MTHFR gene 1298CC homozygote carriers were more susceptible to yield higher plasma homocysteine levels than the 1298AA/AC carriers,with standardized coefficients of 0.086 (P＜0.05) and 0.104 (P＜0.01) of all the participants and the pregnant women,respectively.The MTHFR gene 1793AA homozygote carriers more likely showed higher plasma osteocalcin levels (standardized β=0.091,P＜0.01) than the 1793GG/GA carriers among all the subjects.Plasma homocysteine levels were positively correlated with blood lead levels among the participants and the pregnant women with standardized coefficients of 0.320 (P＜0.01) and 0.179 (P＜0.01),respectively.Plasma osteocalcin levels were positively associated with blood lead levels among pregnant and non-pregnant women with standardized coefficients of 0.084 (P＜0.05) and 0.125 (P＜0.01),respectively.In conclusion,homocysteine and osteocalcin contents in plasma are associated with the MTHFR gene A1298C polymorphism and blood lead levels among pregnant women.The MTHFR gene A 1298C polymorphism-related homocysteine is a possible risk factor for increased blood lead levels among Chinese women.
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Objective To investigate the characteristics of materiome release kinetics of Liuwei Dihuang Pills (LDP), and to evaluate its visualization. Methods According to the 2015 edition of Chinese Pharmacopia, using the evaluation methods of release kinetics of Chinese material medica to determine the materiomics release kinetics and the releasecharacteristic of LDP by the paddle method. Then f2 fit factor was calculated and evaluated on other types of LDP in comparison with water-bindered pills and condensed pills as, which are two most common preparations in the market. Moreover, materiome release spectrum and release increment spectrum were used, hoping to quantify, integrate and visualise the materiome release characteristics of different types of LDP. Results The kinetic characteristics of the LDP accord with the Weibull release model, T50 and Td were calculated, and there are significant differences between different types of pills (P < 0.05) in addition to condensed pills and water pills. Also, some differences and similarities in the materiomics release characteristic by f2 fit factor were found in the study. Materiome release spectrum and release increment spectrum can be used to quantify, integrate and visualise the materiome release characteristics of LDP on different types. Conclusion The materiomics release kinetics can be applied to quantify, integrate and visualise the materiome release characteristic of LDP on different types. Basically in agreement with the saying, “water pills from the facilitation, honey pills take the slow, paste pills from the late of, wax-wrapped pills take the difficult”.
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BACKGROUND:The Specification of Quality Management for Medical Device Production (for Trial Implementation) issued by the China Food and Drug Administration (CFDA) on December 16, 2009 was demanded to be initially implemented in medical device manufacturers with a higher risk in sterility and implant before January 1, 2011. The revised version was published on December 29, 2014 and came into effect on March 1, 2015. OBJECTIVE:To put forward specific suggestions through analyzing the status of 31 sterile implantable medical device manufacturers in Sichuan Province and the corresponding implementation situation of the specification for trial implementation. METHODS:The relevant data of these 31 manufacturers were collected through the quality management system assessment, supervision and inspection, flight inspection and questionnaire survey. And the data were analyzed statistically. RESULTS AND CONCLUSION:The overall size of medical device manufacturers in Sichuan Province is small. There are still some other problems, such as no advanced equipment, low quality of employees, lack of funds and inappropriate management, in these manufacturers. Considering these, we have given some guiding recommendations from the aspects of production and supervision.
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Objective To analyze the outcome of descemet's stripping with endothelial keratoplasty (DSEK) in high-risk rabbit model and its immunological rejection.Methods Together 28 rabbits with corneal neovascularization beyond three quadrants were randomly divided into 2 groups (n =14) according to the surgical procedures,and they were penetrating keratoplasty (PK) and DSEK groups,with the right ones chosen as the experimental eyes in all rabbits.The corneal allograft condition (opacity,edema and neovascularization) was examined by the slit lamp biomicroscopy for 8 weeks,and rejection index (RI) and neovascularization index (NI) were recorded.The corneal sections were stained using hematoxylin-eosin for histopathological evaluation.Then IL-2,IL-10 and vascular endothelial growth factor (VEGF) mRNA expression were quantified by RT-PCR.Results Anterior segment photographs showed corneal opacity,edema and neovascularization appeared in most rabbits of PK group,but few rabbits in the DSEK group did not have above complications.The corneal allograft rejection occurred in 13 eyes (92.9％) in PK group,which was significantly higher than that in DSEK group (4 eyes,28.6％ ％) (P ＜ 0.05).Histology examination showed that more mononuclear cell infiltration appeared in PK group,which was more enhanced than that in DSEK group.Moreover,significantly up-regulation expression of IL-2,IL-10 and VEGF mRNA was observed in PK group when compared with DSEK group.Conclusion These results suggest that corneal allograft rejection has less frequency and less severity after DSEK than after PK,suggesting endothelial keratoplasty could be an ideal strategy for the treatment of corneal endothelial disorders.
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Objective To study the effect of MEK-ERK signaling pathway on diallyl disulfide (DADS)-induced autophagy in human leukemia K562 cells. Methods K562 cells were divided into experimental group, solvent group and blank control group. K562 cells in the experimental group were cultured with 10, 20, 40, 80 mg/L DADS for 48 h. The morphological changes were observed by inverted microscope, monodansyl cadaverine (MDC) staining was used for detecting the formation of the autophagic vacuoles (AV), and the rates of autophagy were analyzed by flow cytometry. Western blot was used to determine the level of expression of ERK, phospho-ERK (p-ERK), LC3-Ⅱ. Results With the increasing of DADS concentration, the number of K562 cells was decreased significantly, and the morphology of some K562 cells became irregular and membrane deformed.The staining of cells and the number of green spots in the cells increased, suggesting that autophagy of the K562 cells cultured with DADS increased. The autophagy rates of K562 cells increased gradually after cultured with DADS for 48 h, the autophagy rate in 40 mg/L DADS group was the highest, and the autophagy rates in 20, 40 and 80 mg/L DADS group were higher than that in the blank control group (P<0.05). There were no significant difference in the expression level of ERK protein between each group (P> 0.05), with the increasing of DADS concentration, the protein expression of p-ERK and LC3-Ⅱ increased, there was significant difference in the protein expression of 40 mg/L DADS group (P<0.05). Conclusion DADS may induce autophagy of K562 cells by activating MEK-ERK signaling pathway through up-regulation of ERK phosphorylation.
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Objective:This study aims to investigate the incidence and potential cause of the undernutrition in gastrointestinal cancer patients received postoperatively adjuvant chemotherapy.Method:Between July and December 2016,a total of 181 gastrointestinal cancer patients who underwent postoperatively adjuvant chemotherapy in the Department of General Surgery of Nanjing General Hospital were enrolled in this study.Nutritional risks of the patients were screened by the patient-generated subjective global assessment (PG-SGA).Serum albumin concentrations,plasma hemoglobin levels and white blood cell numbers of the patients were determined during the chemotherapy.The patients'clinical data,including gender,age,tumor location,chemotherapy stage and adverse events post the chemotherapy,were recorded.Result:All patients completed the PG-SGA for nutritional risk screening.Among the patients,69 cases (38.1％) had a PG-SGA score of 0 ～ 3 points,showing absence of undernutrition.The remaining 112 cases (61.9％)had a PG-SGA score above 4 points,indicating moderate or severe undernutrition.71cases (39.2％) of them displayed moderate underuutrition (4-8 points),and 41 cases (22.7 ％) showing severe undernutrition (＞ 8 points).The PG-SGA scores in patients with gastric cancer were significantly higher than those in the rectal cancer patients (P ＜ 0.05) and in the colon cancer cases (P ＜ 0.01).In addition,the incidence of undernutrition in the male patients was much higher than in the female cases (P ＜ 0.05).The incidence of undernutrition in the patients aging ＞ 65 years was higher than in the cases below 65 years old (P ＜ 0.05).The levels of plasma hemoglobin and numbers of white blood cells were significantly lower in the patients with undernutrition (PG-SGA score ＞4 points),and adverse events such as nausea and vomiting were also more frequently presented in these cases.No significant difference in the incidence of the patients' undernutrition was observed between different stages of the chemotherapy.Conclusion:The patients with gastrointestinal cancer underwent postoperatively adjuvant chemotherapy had higher incidence ofundernutrition.Gender,age and tumor location were the risk factors for the development of undernutrition.Our findings provide evidence for the utilization of nutrition interventions in these patients.
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Objective: To investigate the relationship among powder particle size, cell wall-breaking rate, and dissolution of Liuwei Dihuang Pill (LDP) in vitro. Methods: Particle size and cell wall-breaking rate of four kinds of LDP were measured by laser particle size instrument and optical microscope. The loganin and paeonol were taken as indexes, the feature of dissolution for the above four kinds of LDP was examined by grouting method. Results: There were significant differences in the distribution of particle size, wall-breaking rate, and dissolution among different crushing degrees of LDP. With the decrease of the powder particle size, the wall-breaking rate and relative cumulative dissolution of loganin and paeonol increased. The rate of characteristic cell wall-breaking in the micro powder of Corni Fructus, Alismatis Rhizoma, and Moutan Cortex could reach 100%. Conclusion: Moderately changing degree of smash could cause cell wall-breaking rate changes, so as to control effective ingredient the dissolution rate and extent of Chinese medicine.
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Background It has not been reported that if the visual cortex M receptor changed during the development of myopia and how it changed if given acupuncture treatment.Objective The aim of this study was to observe the effect of electroacupuncture stimulation on the expression of acetylcholine receptors M1 (AchRM1) in visual cortex of guinea with lens-induced myopia (LIM).Methods Forty-eight three-week-old healthy guinea pigs were randomized into the normal control group,the LIM model group and the LIM electroacupuncture group.The right eyes of the guinea pigs were selected as the experimental eyes.LIM was created by monocularly wearing of-10 D lens for 4 weeks in the right eyes in the LIM model group and LIM electroacupuncture group,and then the acupuncture at the temple and hegu point was performed for 30 minutes per day for consequent 4 weeks,in the LIM electroacupuncture group.The fellow eyes of the guinea pigs were used as the self-control eyes.The refractive power and axial length were examined with retinoscopy and A-type sonography before and 4 weeks after modeling,respectively.The animals were sacrificed by excessive anesthesia at the fourth week after acupuncture and visual vertex tissue was obtained.The expression of M1 receptor mRNA in visual vertex was detected by fluorescence quantitative PCR,and the content of M1 receptor protein in visual vertex was assyed by ELISA.The study protocal was approved by Animal Ethic Committee of Shandong University of Traditional Chinese Medicine,and the use and care complied with Statement of the Association for Research in Vision and Ophthalmology.Results At the fourth week after modeling,the mean diopters were (-3.24±0.28) D and (-3.30±0.45) D in the LIM model group and the LIM eleetroacupuncture group,which were significantly higher than (0.83 ±0.86)D in the normal control group (both at P=0.000),and there was no significant difference in the diopter between the LIM model group and the LIM electroacupuncture group (t =0.200,P =0.659).The mean axial lengths were (8.67 ±0.14) mm and (8.60±0.06) mm in the LIM model group and the LIM electroacupuncture group,which were considerably increased in comparison with (8.33±0.08)mm in the normal control group (both at P＜0.05).The relative expression levels of AchRM1 mRNA in visual cortex were 0.79±0.18,1.36±0.23 and 1.13±0.13 in the normal control group,LIM model group and LIM electroacupuncture group,and the relative expression level of AchRM1 mRNA in the LIM electroacupuncture group was significantly higher than that of the normal control group and lower than that of the LIM model group (both at P＜0.05).In addition,the contents of AchRM1 receptor protein in the visual cortex were 248.00±33.31,455.17±42.40 and 396.17±47.57 in the normal control group,LIM model group and the LIM electroacupuncture group,with a similar pattern among the groups (both at P＜0.05).Conclusions A electroacupuncture stimmulation do not affect the myopic diopter and axial length in LIM model.The AchRM1 and AchRM1 receptor in the visual cortex up-regulate in LIM eyes,infering that electroacupuncture stimmulation can improve vision by decreasing the level of AchRM1 receptor in visual cortex in LIM eyes in guinea pigs.
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This study was aimed to explore the effects of blocking B7/CD28 and CD40/CD154 co-stimulatory signals on immune function of sensitized mice', and provide the evidences of acquired immune tolerance for allogeneic bone marrow transplantation. The mice sensitized on 7 day before transplant were divided into 4 groups: (1)CTLA4Ig+ anti-CD154 isotype control IgG; (2)anti-CD154 +CTLA4Ig isotype control IgG; (3)CTLA4Ig and anti-CD154; (4)isotype control IgG of CTLA4Ig and anti-CD154. CTLA4Ig and anti-CD154 used in normal BALB/c mice as isotype control IgG. Each mouse in all groups received CTLA4Ig and anti-CD154 (or corresponding isotype control IgG) 500 µg respectively, and was injected via tail vein on 7 day before transplant. There were 5 mice in each group. The mice were sacrificed on day 0, then the number of CD19(+)CD69(+)B cells, CD44(high)/CD62L(high) and CD44(high)/CD62L(low)/- T cells were measured by flow cytometry. Changes of cytokines and sensitized antibody were tested by ELISA or flow cytometry. The results showed that the numbers of CD19(+)CD69(+)B cells were significantly increased in comparison with the normal group (P < 0.01) , whereas the numbers of cells were significantly decreased when blocking B7/CD28 or /and CD40/CD154 co-stimulatory signals (P < 0.01) . Blocking these 2 signals together displayed a synergistic effect (P < 0.01) . The central memory and effector T cells were defined as CD44(high)/CD62L(high) and CD44(high)/CD62L(low)/- respectively, those increased significantly after sensitized in comparison with those in normal group, whereas their numbers decreased when blocking B7/CD28 or/and CD40/CD154 co-stimulatory signals. Blocking these two signals together, displayed a synergistic effect (P < 0.01). Cytokines, IgG and IgM in all groups were not significantly different. Sensitizing antibody test showed that the fluorescence intensity of sensitized group significantly increased as compared with normal group, whereas fluorescence intensity of CTLA4Ig or/and anti-CD154 treated groups significantly decreased as compared with sensitized group (P < 0.01) . It is concluded that blocking the B7/CD28 or/and CD40/CD154 co-stimulatory signal can inhibit the cellular and humoral immune function, whereas blocking these two signals together displays a synergistic effect.
Subject(s)
Animals , Male , Mice , B7-1 Antigen , Metabolism , Bone Marrow Transplantation , CD28 Antigens , Metabolism , CD40 Antigens , Metabolism , CD40 Ligand , Metabolism , Immune Tolerance , Allergy and Immunology , Mice, Inbred BALB C , Mice, Inbred C57BL , Signal Transduction , Transplantation, HomologousABSTRACT
The aim of this study was to investigate the effects of CD4(+)CD25(+) regulatory T cells (Treg) on allogeneic hematopoietic stem cell transplantation (HSCT) in sensitized mice so as to provide experimental evidence for clinical treatment of allogeneic HSCT rejection in sensitized recipients. The BALB/c mice were divided into 5 groups: group A - mice were sensitized with injection of splenocytes; group B - mice were sensitized with splenocytes and treated with >5×10(5) Treg on day 7 before transplantation; group C - mice were sensitized with splenocytes and treated with 5×10(5) Treg on day 13 and 7 before transplantation; group D - mice were not sensitized, but treated with equal volume of PBS as control; group E - blank control. Each group had 15 mice. On day 0 of transplantation, mice in each group were irradiated lethally with 8 Gy by linear accelerator, and the bone marrow cells of C57BL/6 labeled by fluorescence staining were intravenously injected via the tail vein. The fluorescent cells in peripheral blood and organ tissue were detected by flow cytometry on different time points for homing assessment. Survival rates and hematopoietic reconstitution were also recorded and monitored. The results showed that on 12 and 24 hours after transplantation, as compared with the sensitized group, the number of fluorescence homing cells in different tissue of the applied Treg groups increased significantly and the differences were statistically significant (P < 0.05). The mice in sensitized group and blank control group all died on the 6-13 day, whereas the median survival time of mice in applied Treg once and twice were 15 days and 16 days respectively. Comparing with sensitized group, the difference was statistically significant (P < 0.001), but there was no significant difference between these two groups applied regulatory T cell (P > 0.05). It is concluded that applying Treg can induce immune tolerance of sensitized recipient to allogeneic HSCT and inhibit immune destruction and prolong the survival time, but can not induce full immune tolerance and at last sensitized mice died of rejection of hematopoietic stem cells.
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Animals , Male , Mice , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Methods , Immune Tolerance , Mice, Inbred BALB C , Mice, Inbred C57BL , T-Lymphocytes, Regulatory , Allergy and Immunology , Transplantation, HomologousABSTRACT
Objective To observe the changes of behavior,blood cortisol level,glucocorticoid receptors (Grs) and mineralocorticoid receptors (MRs) in hippocampus area after four weeks of unpredictable chronic mild stress,and to investigate the probable role of hypothalamus-pituitary-adrenal (HPA) axis in the pathogenesis of depression in aged people.Methods Aged male Wister rats were randomly assigned to control group and model group.The model group received unpredictable mild stress,including food and water deprivation,restrain,tail clipping,forced swimming,white noise,cage titling and cage rotating for 4 weeks,while the control group was undisturbed unless routine feeding and cage changing.After 4 weeks of procedure,the behavior changes were assessed by sucrose intake test,open-field test and state evaluation,serum cortisol level was measured by chemiluminescent assay,the qualitation and quantitation of GRs and MRs in hippocampus area were evaluated by immunohistochemistry and Western blotting respectively.All data were analyzed by using t-test.Results Body weight,the grooming score,activities in openfield test,food intake and sucrose intake were decreased in model group as compared with control group after 2 weeks of chronic mild stress (all P＜0.01),suggesting the stress induced depressive-like behavior effects on aged rats.Serum cortisol level was elevated in model group as compared with control group after 4 weeks of chronic mild stress (P＜0.01).A decrease of the neurons was found in CA3 of hippocampus,but not in DG area.In CA3 area,GR positive neurons were decreased,but no significant decrease was found in MR positive neurons.Conclusions The chronic mild stress leading to depressive-like behavior effects in aged rats induces overall HPA axis dysfunction,elevation of serum cortisol level,impairment of hippocampus neurons and decrease of GR positive neurons.The HPA axis dysfunction induced by chronic mild stress may play an important role in the pathogenesis of depression.
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This research was aimed to explore the effects of blocking B7/CD28 and CD40/CD154 co-stimulatory signals on engraftment of hematopoietic stem cell in the sensitized recipient so as to provide the experimental evidence for the treatment of sensitized recipient's immune rejection after clinical allogeneic hematopoietic stem cell transplantation (HSCT). The BALB/c mice were divided into 4 groups: (1)mice sensitized on 7 day before transplant; (2)mice were sensitized on 7 day before transplant, and injected CTLA4Ig+anti-CD154 applied; (3)normal mice injected by corresponding isotype control IgG of CTLA4Ig and anti-CD154; (4)normal blank control mice. Each group had 15 mice. On day 0, mice of each group were irradiated lethally 8 Gy by linear accelerator, and the bone marrow cells of C57BL/6 labeled by fluorescence staining were injected via the tail vein. The fluorescent cell level in peripheral blood and organ tissue at different time points were detected by flow cytometry (FCM) for homing assessment. Survival rates and hematopoietic reconstitution were also monitored and recorded. The results showed that application of CTLA4Ig anti-CD154 could promote implantation of allogeneic HSC in sensitized recipients, induce the immune tolerance, prolong their survival time and accelerate the hematopoietic reconstitution within 28 days, compared with the sensitized group. It is concluded that applying CTLA4Ig and anti-CD154 can enhance the engraftment of HSCT and induce immune tolerance in the sensitized recipient after allogeneic HSCT and accelerate the hematopoietic reconstitution.
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Animals , Male , Mice , Abatacept , B7 Antigens , CD28 Antigens , CD40 Antigens , CD40 Ligand , Graft Rejection , Hematopoietic Stem Cell Transplantation , Immune Tolerance , Immunoconjugates , Pharmacology , Mice, Inbred BALB C , Mice, Inbred C57BL , Transplantation, HomologousABSTRACT
<p><b>OBJECTIVE</b>To compare the performance of full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT) in the assessment of the lesions in dense breast, and to estimate the difference in diagnosis of breast disease by FFDM images alone and FFDM plus DBT images.</p><p><b>METHODS</b>According to the breast imaging reporting and data system (BIRADS), 134 patients were selected. The morphology of the lesions shown on FFDM and DBT were evaluated and compared, and the maximum diameter of the lesions was measured. At first, doctors made the diagnosis of a patient by reading FFDM only. Then they made another diagnosis by combining with DBT images of the same patient. The two diagnoses were compared and analyzed according to the pathology results.</p><p><b>RESULTS</b>One hundred and thirty-four patients were included in this study, and all of them were confirmed by histology (65 benign cases, 69 malignant cases). DBT could show more details about the morphology of the lesions, including the border of the masses, spiculation and vessels. The numbers of those signs detected by DBT were 46, 30 and 3, respectively, while only 33 case with circumscribed masses and 14 cases with spiculation were detected by FFDM. Only the difference of spiculation in heterogeneously dense breast detected by DBT and FFDM was statistically significant (P < 0.05). Of the cases with calcifications, DBT images (reconstructed as a 1-mm-thick slice) showed calcifications superior to FFDM in 2 cases, equal to FFDM in 23 cases, and inferior to FFDM in 11 cases. The difference was statistically significant (P < 0.05). But when thickness was changed into 1 cm, the visibility of calcifications in those cases was equal between FFDM and DBT. The maximum diameter of lesions was 2.46 ± 1.64 cm in DBT image, and 2.58 ± 1.62 cm in FFDM image, with a significant difference (P < 0.05). Comparing with reading FFDM images only, the accuracy of FFDM combining with DBT was increased from 88.8% to 91.8%. For FFDM, the AUC of ROC was 0.887, while for DBT it was increased to 0.912, with a non-significant difference (P > 0.05).</p><p><b>CONCLUSIONS</b>DBT is superior to FFDM in the morphological characterization and small calcification in the lesions in dense breast. Combining FFDM and DBT improves the accuracy of diagnosis, but the difference is not statistically significant.</p>
Subject(s)
Adolescent , Adult , Female , Humans , Middle Aged , Young Adult , Breast Diseases , Diagnostic Imaging , Breast Neoplasms , Diagnostic Imaging , Calcinosis , Diagnostic Imaging , Carcinoma in Situ , Diagnostic Imaging , Carcinoma, Ductal, Breast , Diagnostic Imaging , Fibroadenoma , Diagnostic Imaging , Image Processing, Computer-Assisted , Imaging, Three-Dimensional , Mammography , Methods , Radiographic Image Enhancement , Tomography, X-Ray ComputedABSTRACT
<p><b>OBJECTIVE</b>To explore the feasibility of volume perfusion CT imaging to dynamically monitor and evaluate the response of rabbit VX2 soft-tissue tumor to antiangiogenic treatment.</p><p><b>METHODS</b>To establish an experimental animal model of VX2 soft tissue tumor on 20 New Zealand white rabbits. Twenty rabbits were randomly divided into 2 groups. The therapy group was treated with recombinant human endostatin (3 mg·kg⁻¹·d⁻¹) for 7 days, and the control group received saline in the same dose only. Four times of CT volume perfusion scan were performed before treatment and on the second, forth, seventh days of treatment, respectively. The value of blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability (PMB) in the VX2 tumors were measured after scanning. The microvessel density (MVD) and expression of vascular endothelial growth factor (VEGF) in the tumors were determined using immunohistochemical staining.</p><p><b>RESULTS</b>The tumor volume of the therapy group was (1.36 ± 0.73) cm³ on the forth day of treatment and (1.69 ± 0.68) cm³ on the seventh day of the treatment. The tumor volume of the control group was (2.35 ± 0.62) cm³ on the fourth day of treatment and (3.87 ± 0.93) cm³ on the seventh day of the treatment (P < 0.05). On the seventh day of treatment, tumor necrosis ratio of the therapy group and the control group was (25.58 ± 5.51)% and (42.93 ± 4.34)%, respectively (P < 0.05). Comparing the perfusion parameters between the two groups on the same day, and the second, forth, seventh days of treatment, the value of PMB of the therapy group was (70.36 ± 23.46) ml·100 ml⁻¹·min⁻¹, (79.64 ± 13.68) ml·100 ml⁻¹·min⁻¹ and (84.76 ± 3.55) ml·100 ml⁻¹·min⁻¹, respectively, and that in the control group was (26.61 ± 6.47) ml·100 ml⁻¹·min⁻¹, (33.74 ± 16.47) ml·100 ml⁻¹·min⁻¹ and (30.47 ± 10.64) ml·100 ml⁻¹·min⁻¹, respectively (P < 0.05). The value of BF in the therapy group and control group was (71.19 ± 12.21) ml·100 ml⁻¹·min⁻¹ and (43.56 ± 12.21) ml·100 ml⁻¹·min⁻¹, respectively, on the seventh day of treatment (P < 0.05). The parameters on different days in the same group were compared. In the control group, the value of BF on the seventh day of treatment was significantly lower than that before and on the second and forth days of treatment (P < 0.05). However, in the therapy group, the value of PMB on the second, forth, and seventh days of treatment was significantly higher than that before treatment (P < 0.05). MVD of tumor in the control group was increased gradually, whereas increased on the first day and then decreased more in the therapy group. The VEGF expressions did not differ significantly between the experimental and control groups.</p><p><b>CONCLUSIONS</b>Volume perfusion CT is helpful to quantify the tumor perfusion and evaluate the functional changes of tumor vasculature, and then evaluate the early therapeutic effect of antiangiogenic treatment.</p>