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White matter lesions in patients with obstructive sleep apnea hypopnea syndrome (OSAHS) are common brain microstructural changes, the mechanism of which is still not clear, including decreased cerebral perfusion, oxidative stress, inflammatory damage, etc. At present, white matter lesions are mainly evaluated by magnetic resonance imaging. White matter lesions in patients with OSAHS are often manifested as cognitive dysfunction such as inattention, decreased executive ability and memory loss. Continuous positive airway pressure can relieve the white matter lesions and improve the cognitive function of some patients with OSAHS. Further study on the pathogenesis and early imaging characteristics of OSAHS white matter lesions is expected to provide targets and evidence for early intervention.
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Objective:To investigate the influence of preoperative thyroid dysfunction on the 30-day postoperative mortality and complications in elderly patients with hip fracture.Methods:A retrospective analysis was conducted of the 349 elderly patients with hip fracture who had been admitted to Department of Orthopedic Trauma, Beijing Luhe Hospital Affiliated to Capital Medical University from January 2018 to December 2019. They were 108 males and 241 females, with an average age of 76.3 years (from 60 to 104 years). There were 190 femoral intertrochanteric fractures and 159 femoral neck fractures. By the preoperative level of thyroid function, the patients were divided into a normal function group of 290 cases and a dysfunction group of 59 cases. The 2 groups were compared in terms of hospital stay, mortality and incidence of complications within 30 days postoperation.Results:In this cohort, the rate of 30-day postoperative mortality was 3.4%(12/349) and the incidence of 30-day postoperative complications 14.6%(51/349). The 2 groups were comparable because there was no significant difference between them in the preoperative general data except for the preoperative comorbidity of coronary heart disease ( P>0.05). In the dysfunction group, the hospital stay averaged (10.2±6.9) d, the rate of 30-d postoperative mortality 1.7%(1/59) and the incidence of 30-day postoperative complications 16.9%(10/59), which were insignificantly different from those in the normal function group [(10.7±7.5) d, 3.8%(11/290) and 14.1%(41/290), respectively] ( P> 0.05). Conclusion:Since preoperative thyroid dysfunction does not affect the 30-day postoperative mortality and postoperative complications in the elderly patients with hip fracture but no definite thyroid disease, routine thyroid function screening is not recommended for them.
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Objective To explore the correlation between exon region polymorphism of PPP1R3A gene and schizophrenia in Uygur Chinese population. Methods PPP1R3A gene exon region DNA amplification was performed using multiple PCR targeted capture next-generation sequencing method in 528 patients with schizophrenia and 576 healthy controls of Uyghur descent, Illumina HiSeq X Ten was used for sequencing, the symptoms of schizophrenia were assessed by positive and negative symptoms scale (PANSS). Results The allelic and genotypic distributions in rs1800000 of PPP1R3A gene between patients with schizophrenia and healthy controls had significant difference (P＜0.05), rs1799999 in genotype frequency between the female case and control groups showed significant difference (P＜0.05). Furthermore, the allelic distributions of rs8192686 between male cases and controls had significant difference (P＜0.05). Conclusion PPP1R3A gene rs1800000 may be associated with the development of schizophrenia in Uygur Chinese population; rs1799999 may be a risk factor for susceptibility of female Uygur Chinese schizophrenia; The C allele at rs8192686 may be associated with male Uygur Chinese schizophrenia.
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Objective To explore the influence of cucurbitacin E (CuE) on autophagy in human bladder cancer cell line T24 and further study its impacts on cell proliferation. Methods MTT assay was used to determine the proliferation inhibition capacity of CuE on T24 and western blot to check the impacts of CuE treatment on the expression of classic autophagy markers LC3A/B and p62. LC3 turnover assay and GFP-RFP-LC3 fluorescent assay were performed to determine autophagy flux. Western-blot was used to check the autophagy inhibition ability of 3-MA on CuE treatment and MTT assay and cell counting assay were used to check the influence of CuE-induced autophagy on cell proliferation with/without autophagy inhibition. Results CuE inhibited the proliferation of T24 and the IC50 in 24 h was about 0.75 μmol/L. CuE treatment increased the expression of LC3A/B Ⅱ and LC3A/B Ⅱ/Ⅰ ratio (P < 0.05) , but decreased the expression of p62 (P < 0.05) , indicating the induction of autophagy. Autophagy flux was induced because of positive LC3 turnover assay and the increase of yellow and red dots in GFP-RFP-LC3 fluorescent assay (P < 0.05). CuE-induced autophagy was inhibited by 3-MA (P < 0.05). With autophagy inhibition, CuE's proliferation suppression ability on T24 was attenuated (P <0.05). Conclusion CuE induces autophagy in bladder cancer cell line T24 and the induced autophagy positively contributes to the inhibitation of cell proliferation.
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Objective To investigate the clinical indicators which could be used to differentiate incarcerated stones from unincarcerated stones by comparing clinical characteristics of patients.Methods 96 patients who were diagnosed as ureteral stones treated by ureteroscopic lithotripsy (URSL) from June 2017 to November 2017 were selected in the study.Clinical characteristics of patients were collected.The total study consisted of 62 male and 34 female patients.The patients' age ranged from 24 to 78 years old and average age was (54.5 ± 12.7) years old.There were 35 patients were diagnosed as ureteral stones with hypertension,9 patients with diabetes,85 patients with hydronephrosis,respectively.The number of patients,whose stone located in upper ureters,middle ureters and lower ureters were 49,19,28,respectively.The average of maximum stone diameter,maximum cross-sectional area of the stone,stone volume,hounsfield units of stone and maximum ureteral wall thickness (UWTmax) at the stone site were (7.75 ± 2.68) mm,(36.12 ± 24.43) mm2,(304.06 ± 303.39) mm3,(755.75 ± 318.05) HU,and (3.18 ± 1.13) mm,respectively.Percussion tenderness over kidney region were positive in 11 cases,weak positive in 64 cases and negative in 21 cases,respectively.Stone-free rate after operation were 93.8％.Patients were divided into two groups,incarcerated or unincarcerated,and statistical differences between clinical characteristics of the two groups were analyzed by univariate analysis.The differences were further compared by multivariate logistic regression analysis to find independent predictors of impacted stones.The ROC curve was used to find the optimal UWT for diagnosis of impacted stone.The accuracy of this value was evaluated and patients were grouped by this value to compare the differences between groups.Results The operation and follow-up were successfully performed in all patients.Univariate analysis showed there were no statistical significance differences in gender [(24 males and 16 females)vs.(38 males and 18 females)],age [(53.4 ± 12.3) years vs.(48.7 ± 12.7) years],previous history of diabetes (4 cases vs.5 cases) and stone location [(19 upper stones,9 middle stones,12 lower stones) vs.(30 upper stones,10 middle stones,16 lower stones)],between the two groups (P ＞ 0.05).Among the clinical characteristics of patients in incarcerated and unincarcerated groups,UWTmax were (4.15 ± 0.94) mm and (2.58 ± 0.76) mm,previous history of hypertension were 20 cases and 15 cases,ipsilateral URSL history were 14 cases and 10 cases,hounsfield units of stone were (847.66 ± 282.39) HU and (698.65 ± 325.50) HU,hydronephrosis were 40 cases and 50 cases,maximum stone diameter were (8.67 ± 2.28)mm and (7.17 ± 2.75)mm,maximum cross-sectional area of the stone were (43.83 ± 23.65) mm2 and (31.14 ± 23.64) mm2,stone volume were (386.20 ± 296.60) mm3 and (253.04 ± 296.29) mm3,percussion tenderness over kidney region were positive in 8 cases(20.0％),weak positive in 27 cases,negative in 5 cases and positive in 3 cases,weak positive in 37 cases,negative in 16 cases,respectively.The difference was statistically significant (P ＜ 0.05).Multivariate logistic regression analysis showed UWTmax (OR =10.40,P ＜ 0.001) at the stone site was significantly correlated with impacted ureteral stones and it was an independent predictor of impacted stones.ROC curve analysis showed that the optimal cut-off value of UWTmax was 3.26 mm.The sensitivity of the value to predict impacted stone is 82.5％ and the specificity is 87.5％.Depending on the cut off value of 3.26 mm,cases were divided into two groups,40 cases were in high UWTmax (≥3.26 mm)group and 56 cases were in low UWTmax (＜ 3.26 mm)group.Higher UWTmax was accompanied with a higher incidence of ureteral edema[77.5％ (31/40) vs.32.1％ (18/56)],polyps [30.0％ (12/40) vs.7.1％ (4/56)],strictures[37.5％ (15/40)vs.12.5％ (7/56)] and a lower stone-free rate[87.5％ (35/40) vs.98.2％ (55/56)].The difference was statistically significant (P ＜ 0.05).Conclusions UWTmax can be used to differentiate impacted stones from unimpacted stones before surgery.The patients with Higher UWTmax (≥3.26 mm) was accompanied with a higher incidence of stone impacted,ureteral edema,polyps,and strictures,and a lower rate of stone clearance.
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Objective To investigate the effect of Teach-back mission pattern in the education of elderly patients with metabolic syndrome.Methods A total of 110 elderly patients with metabolic syndrome who were admitted to the hospital from October 2015 to September 2017 were selected as study subjects and randomly divided into observation group and control group with 55 cases each by random digits table method.The control group was given traditional health education,and the observation group was given Teach-back missionary model.After 6 months of follow-up,the health literacy levels of the two groups before and after intervention were measured using the Scale on Health Literacy for Patients with Chronic Disease.The systolic blood pressure (SBP),diastolic blood pressure (DBP),body mass index (BMI),waist circumference (WC),fasting plasma glucose (FPG),glycosylated hemoglobin (HbA1c),triglyceride (TG),and total cholesterol (TC) levels were compared before and after the intervention of the two groups of patients.Results The cases of loss of contact and withdrawal were removed.In the follow-up period of 6 months,52 patients and 49 patients in the observation group and the control group completed the study.The scores of the observation group's information acquisition ability,exchange interaction ability,improvement of health willingness,and economic support willingness were (27.18 ±4.15),(29.63 ± 4.56),(14.63 ± 2.07),(7.85 ± 1.23) points,respectively.All were significantly higher than the control group (23.96 ± 3.83),(26.34 ± 3.87),(13.04 ± 1.56),(6.91 ± 0.93) points,and the difference was statistically significant (t =3.898-4.339,all P＜ 0.05).During follow-up of 6 months,the awareness rate of disease knowledge and the compliance rate of health behaviors in the observation group were 92.31％(48/52) and 69.39％(34/49),respectively,which were significantly higher than those in the control group,86.54％ (45/52) and 63.27％ (31/49).The difference was statistically significant (x2=8.677,7.336,P＜ 0.01).During follow-up of 6 months,SBP,DBP,BMI,and WC in the observation group were (135.73 ±8.53) mmHg(1 mmHg=0.133 kPa),(85.69 ± 8.74) mmHg,(23.76 ± 1.91) kg/m2,(87.13 ± 6.45) cm,respectively,those in the control group were (141.79±7.24) mmHg,(89.45±8.37) mmHg,(24.98 ± 2.03) kg/m2,and (90.13 ± 6.74) cm,respectively,,and the difference was statistically significant (t =2.206-3.831,P＜ 0.05).The FPG,HbA1c,TG,and TC in the observation group were (6.57 ± 0.91) mmol/L,(5.85 ±1.03)％,(1.71 ± 0.68) mmol/L,and (4.67 ± 0.68) mmol/L,respectively,which were significantly lower than those of the control group.The control group values were (7.24 ± 1.03) mmol/L,(6.46 ± 1.14)％,(1.98 ±0.63) mmol/L,(4.98 ± 0.72) mmol/L.The difference was statistically significant (t =2.167-3.469,P ＜0.05).Conclusions The Teach-back mission pattern can significantly improve the level of health literacy in elderly patients with metabolic syndrome,improve their physical and metabolic indicators,and has important implications for preventing and treating various chronic diseases and improving life quality.
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Objective To investigate the differences in susceptibility to Lewis lung carcinoma and T lymphocyte subsets in the immune microenvironment between young and elderly mice.Methods Six C57/B6 mice at two months(young)and six mice at twelve months(aged)were injected with Lewis lung carcinoma cells at the dose of 1 × 106 in the left armpit to establish a murine model of lung carcinoma.The weight and tumor growth were monitored.Blood samples for routine blood tests were collected after 24 days.The proportions of CD4+ and CD8+T cells in the spleen were detected by flow cytometry,and the infiltration of CD4+,CD8+ T cells and related effector T cells in the tumor microenvironment were determined in the same way.Results The body weight of tumor bearing mice in the aged group was significantly higher than that in the young group(P ＜0.001);The tumor weight in the aged group(5.084±0.528)g was significantly higher than that in the young group(2.963 ±0.378)g(t =3,349,P =0.012);Routine blood tests showed that the numbers of leukocytes and subsets(except mononuclear)in the aged group were significantly lower than in the young group(P ＜0.05);Flow cytometry found that the effector and memory/effector CD4+T cell ratios in the spleen were significantly higher in the aged group than in the young group(P ＜0.001)and the expression of effector and memory/effector CD8+T cells in the tumor microenvironment was also significantly higher than in the young group(P ＜0.05);Quantitative expression values of IL-6 and IL-10 in the tumor microenvironment were 25090±3820 and 10670± 1793 in the aged group and 6252±864 and 3061±451 in the young group,respectively.Moreover,the expression levels of IL-6 and IL-10(t =3.925,P =0.01;t =3.552,P =0.02)in the tumor microenvironment in the aged group were significantly lower than those in the young group.Conclusions Young mice are more susceptible to Lewis lung carcinoma,probably as a result of differences in inflammation and immunity.
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Objective To investigate the anti-injury and anti-inflammation protective effects of metformin in acute-liver-injury SD rat model induced by D-galactosamine and Pam3CSK4 .Methods Eighteen male Sprague-Dawley rats were treated with the mixture of D-galactosamine (350 mg/kg ) and Pam3CSK4 (50 μg/kg ) by intraperitoneal injection (i .p .) to construct acute liver injury model .The rats in intervention group were given PBS and metformin ,respectively .The liver and body weight were measured and the ratio of liver weight to body weight was calculated .HE staining was used to observe the pathological changes of the liver .Fasting serum was collected for detection of serological parameters .ELISA and RT-qPCR were used to determine the expression levels of IL-6 and TNF-α.Finally , activation of MAPK signal pathway in rat liver was detected by Western blot .Results Compared with those in control group , the ratio of body weight to liver weight , serum transaminase and proinflammatory cytokines IL-6 and TNF-a were all significantly increased in the two intervention groups .Meanwhile , hepatic degeneration and hepatic interstitial exudation indicated that D -galactosamine combined with Pam3CSK4 successfully constructed acute liver injury model in the SD rats.Compared with PBS group, the ratio of body weight to liver weight , hepatic damage , serum transaminase levels.and the expressions of proinflammatory cytokines IL-6 and TNF-a were significantly decreased in metformin-treated group.Meanwhile,the expressions of p-ERKl/2,p-SAPK/JNK and p-P38 MAPK decreased in liver tissues by metformin pretreatment,suggesting that metformin may play an anti-inflammatory effect by suppressing MAPK signaling pathway.Conclusion Metformin attenuated inflammatory reactions in SD rats with acute liver injury induced by D -galactosamine and Pam3CSK4.
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Objective To investigate the effects of gefitinib on early embryonic development and expression of abcb4 tumor resistance genes in zebrafish.Methods Zebrafish were adopted as experimental animals and divided into gefitinib group,mixture of doxorubicin and gefitinib group and blank group.Zebrafish embryos of 0.5-1.5 hours after fertilization(0.5-1.5 hpf) were exposed to different concentrations of gefitinib,and then embryo development of zebrafish in 24-120 hpf was observed and the number of death,hatch and malformation was recorded.The embryo mortality was calculated under different concentrations of gefitinib at different time points,and the numerical value of IC50 was calculated;Hatching rates of zebrafish embryo in 48 hpf and 72 hpf and malformation rates of zebrafish embryo in 120 hpf were calculated.The zebrafish embryos exposed to different concentrations of gefitinib in different groups were collected,and the expressionof abcb4 gene in zebrafish embryos was detected by real-time quantitative PCR.Results Gefitinib IC50 in zebrafish embryos was 16.18 μmol/L.Compared with the control group,higher dosage (20 μmol/L) of gefitinib in other two groups significantly decreased hatching rates of embryos,and had obvious embryonic lethal effects and teratogenic effects.Moreover,the mRNA levels of the abcb4 gene in the zebrafish embryos of gefitinib group were not significantly changed,whereas the mRNA levels of the abcb4 gene in mixture of doxorubicin and gefitinib group were significantly different(P＜0.05).Conclusion Gefitinib has no significant effects on the expression of abcb4 tumor resistance gene in early development of zebrafish embryos(P＞0.05),but it can reverse the drug resistant effects of doxorubicin,suggesting that zebrafish can construct tumor resistance model.
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OBJECTIVE Identification of novel autophagy inhibitors for the combinational treatment of non-small cell lung cancer (NSCLC). METHODS MTT assay and annexin V/PI staining assay were used to evaluate the cell proliferation and apoptosis, respectively. Immunofluorescence staining and cathepsin activity assay were used to detect autophagy. Small interfering RNA was performed to silence the genes and Western blot assay was used to evaluate the protein express levels. Xenograft experiments were applied for in vivo evaluation. RESULTS Cepharanthine, a natural compound, increased LC3-II expression and GFP-LC3 puncta formation in NSCLC NCI-H1975 cells. Numerous yellow puncta were observed in cepharanthine- treated cells with mRFP- EGFP- LC3 transfection. Co-staining of GFP-LC3 with LysoTracker red or LAMP1 antibody suggested that cepharanthine inhibits autophagosomes- lysosomes fusion. Moreover, cepharanthine attenuated the lysosomal cathepsins maturation. We also confirmed that dacomitinib induced cytoprotective autophagy. Combined treatment with cepharanthine increased the anti- cancer effects of dacomitinib in vitro and in vivo. Besides, cepharanthine could not enhance the anti-cancer effect of dacomitinib in autophagy deficient cells. CONCLUSION Cepharanthine might be further developed as a promising autophagic inhibitor, and combined treatment cepharanthine with dacomitinib could pose as an effective strategy for NSCLC treatment.
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Objective To evaluate whether individualized dosage regimen based on therapeutic drug monitoring (TDM) is beneficial for improving the rate of pharmacokinetics/pharmacodynamics (PK/PD) reaching the standard and anti-infection efficacy. Methods Totally, 36 cases in the intensive care unit ( ICU ) of Nanjing Drum Tower Hospital using meropenem during January 2015 to December 2015 were collected, and divided into intervention group and control group. Results On the fourth day of administration, meropenem concentration in intervention group was significantly higher than that of the control group (22.5 μgmL-1 and 17.5 μgmL-1, respectively, P=0.007).With minimal inhibitory concentration (Cmin)>8 μgmL-1 serving as target, the rate of reaching the standard was both 22. 2% on day 2, 100. 0% and 72. 2% on day 4 in intervention group and control group, respectively (P=0.015). With minimal inhibitory concentration (Cmin) >32 μgmL-1 serving as target, the rate of reaching the standard was both 0 on day 2, 38. 9% and 5. 5% on day 4 in intervention group and control group, respectively (P=0.015). The clinical curative rate of the intervention group and control group was 83.3% and 72.2%, respectively (P=0.437), and the failure rate was 16.7% and 27.8%, respectively.Bacteria clearance rate was 88.9%and 55.5% in the intervention group and control group, respectively(P<0.05). Conclusion Individualized dosage regimen based on TDM in ICU patients is beneficial to improving the rate of PK/PD reaching the standard and anti-infection efficacy.
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Objective To evaluate whether individualized dosage regimen based on therapeutic drug monitoring (TDM) is beneficial for improving the rate of pharmacokinetics/pharmacodynamics (PK/PD) reaching the standard and anti-infection efficacy. Methods Totally, 36 cases in the intensive care unit ( ICU ) of Nanjing Drum Tower Hospital using meropenem during January 2015 to December 2015 were collected, and divided into intervention group and control group. Results On the fourth day of administration, meropenem concentration in intervention group was significantly higher than that of the control group (22.5 μgmL-1 and 17.5 μgmL-1, respectively, P=0.007).With minimal inhibitory concentration (Cmin)>8 μgmL-1 serving as target, the rate of reaching the standard was both 22. 2% on day 2, 100. 0% and 72. 2% on day 4 in intervention group and control group, respectively (P=0.015). With minimal inhibitory concentration (Cmin) >32 μgmL-1 serving as target, the rate of reaching the standard was both 0 on day 2, 38. 9% and 5. 5% on day 4 in intervention group and control group, respectively (P=0.015). The clinical curative rate of the intervention group and control group was 83.3% and 72.2%, respectively (P=0.437), and the failure rate was 16.7% and 27.8%, respectively.Bacteria clearance rate was 88.9%and 55.5% in the intervention group and control group, respectively(P<0.05). Conclusion Individualized dosage regimen based on TDM in ICU patients is beneficial to improving the rate of PK/PD reaching the standard and anti-infection efficacy.
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Objective To explore the effects of vinblastine on abcb4 tumor resistance gene expression in early development zebrafish and lay an important foundation for multi-drug resistant antineoplastic screening in zebrafish model.Methods Zebrafish embryos of 0.5~1.5 hours post-fertilization were exposured to different concentrations of vinblastine, and then calculated the IC50 of vinblastine.Zebrafish embryos of 0.5~1.5 hours post-fertilization were treated with different concentrations of vinblastine and embryo culture medium respectively, and then observed zebrafish embryo development in 24~120 hours post-fertilization and recorded the number of death, hatch and malformation.Evaluating the impact of vinblastine on abcb4 gene expression in zebrafish with quantitative real-time PCR and whole-mount in situ hybridization by collecting zebrafish embryos exposed to different concentrationsof vinblastine.Results Vinblastine IC50 in zebrafish embryos was 3.08 μmol/L.The mRNA level of abcb4 gene in vinblastine treated embryos was significantly increased compared to blank control group.Moreover, abcb4 gene positive hybridization signals were found in the small intestine of zebrafish embryos after 120 hours post-fertilization and also found in the brain and heart of zebrafish embryos by the method of whole-mount in situ hybridization.Conclusions Vinblastine can significantly increase the expression level of abcb4 tumor resistancegene in early development zebrafish embryos, which indicates that zebrafish can be used as a tumor resistant drug screening model.
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The present study aimed to examine the value of ultrasonic soft markers in prenatal screening by analyzing the clinical outcome of fetuses with ultrasonic soft markers during the second trimester of pregnancy.A retrospective analysis was performed to evaluate the outcome of 591 fetuses with ultrasonic soft markers from January 2015 to August 2016 in Zhongnan Hospital of Wuhan University,China.It was found that 591 fetuses showed ultrasonic soft markers in 4927 cases with the occurrence rate being 12.0％.Among them,564 fetuses (95.4％) were delivered and the remaining 27 cases (4.6％) were aborted.Five hundred and sixty-seven cases had single ultrasonic soft marker,including echogenic intracardiac focus (n=343),mild renal pelvis dilatation (n=116),short long bones (n=72),single umbilical artery (n=31),mild lateral ventriculomegaly (n=21),choroid plexus cysts (n=19),and echogenic bowel (n=13),with the disappearing rates in pregnancy being 97.1％ (333/343),77.6％ (90/116),0％ (0/72),0％ (0/31),57.1％ (12/21),89.5％ (17/19) and 61.5％ (8/13) respectively.The rate of pregnancy termination due to single ultrasonic soft marker was 3.4％ (19/567),and that was 33.3％ (8/24) due to two ultrasonic soft markers with the difference being statistically significant (P＜0.05).The reasons of pregnancy termination included malformations (polycystic kidney,cleft lip and palate,congenital heart diseases,pcromphalus,hypospadias,hydrocephalus),chromosome abnormality,and stillbirth.It was concluded that single ultrasonic soft marker is usually transient manifestation in pregnancy.Without the other structural defects,single ultrasonic soft marker usually disappears spontaneously with favorable prognosis in a low-risk population.It is suggested that ultrasonic soft markers should be appropriately interpreted to avoid unnecessary invasive examination.
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Objective To detect the expression level of Taurine up?regulated gene 1( TUG1) in the re?nal cell carcinoma and paired paracancerous normal tissues,then explore the relationships between the expression level of TUG1 and clinical characteristics.Methods RNA was Extacted from the resected renal cell carcinoma tissues and paired paracancerous normal tissues of 46 patients respectively,by reverse transcription to get cDNA, the expression level of the TUG1 was detected by RT?qPCR, the relationship between the expression level of TUG1 and the clinicopathological characteristics was analyzed by statistically software. Results The expression of TUG1 in renal cell carcinoma was obviously lower than that in paired paracancerous normal tissues(0.533±0. 027 vs. 1.000±0.298,t=-3.350,P0.05).Conclusion The expression of TUG1 in renal cell carcinoma tissues are down?regulated,which also suggest that it may be re?lated to the tumorigenesis and development of renal cell carcinoma.
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<p><b>OBJECTIVE</b>To determine the effect of the combination of lapatinib with chlorogenic acid on metastasis of breast cancer in mouse model.</p><p><b>METHODS</b>The classical macrophage M2 polarization model induced by interlukin13in vitro was adopted in the study. Flow cytometric analysis was performed to detect the expression of M2 marker CD206. The transcription of M2-associated genes was measured by RT-PCR. HE staining was used to analyze the metastatic nodes of breast cancer in lungs of MMTV-PyVT mice. Immunostaining analysis was used to detect the expression of related proteins in breast cancer.</p><p><b>RESULTS</b>The combination of lapatinib and chlorogenic acid inhibited the expression of CD206 induced by IL-13[(42.17%±2.59%) vs (61.15%±7.58%), P<0.05]. The combination more markedly suppressed expression of M2-associated gene Ym1 than lapatinib alone[(0.9±0.1) vs (1.8±0.0), P<0.05]. The combination of lapatinib and chlorogenic acid significantly reduced metastatic nodes in lung[P<0.05], and also significantly decreased the percentage of CD206(+) cells in breast cancer compared to controls[(6.08%±2.60%) vs(29.04%±5.86%), P<0.05].</p><p><b>CONCLUSION</b>The combination of lapatinib and chlorogenic acid can effectively inhibit macrophage M2 polarization and metastasis of breast cancer.</p>
Subject(s)
Animals , Female , Mice , Chlorogenic Acid , Pharmacology , Lung Neoplasms , Drug Therapy , Macrophages , Mammary Neoplasms, Experimental , Drug Therapy , Neoplasm Metastasis , Drug Therapy , Quinazolines , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To evaluate the anti-tumor effect of the combination of suberoylanilide hydroxamic acid(SAHA) with statins(lovastatin or simvastatin) on non-small cell lung carcinoma(NSCLC) cells.</p><p><b>METHODS</b>Human NSCLC A549 cells were treated with SAHA in combination of lovastatin or simvastatin. The cell growth was analyzed by SRB method, and the apoptosis of A549 cells was assessed by flow cytometer. The expression of cleaved poly-ADP-ribose polymerase(cleaved-PARP) and p21 protein was analyzed by Western-blotting when A549 cells were challenged with 2.5μmol/L SAHA and 5μmol/L lovastatin.</p><p><b>RESULTS</b>Lovastatin and simvastatin synergized SAHA in the inhibition of A549 cells. SAHA induced apoptosis was also enhanced by lovastatin. Treatment with 2.5μmol/L SAHA significantly up-regulated the expression of p21 protein in 48 h, while the protein expression was reduced in combined treatment with 5μmol/L lovastatin.</p><p><b>CONCLUSION</b>Statins can synergize the anti-tumor effect of SAHA in human NSCLC cells through a p21-dependent way.</p>
Subject(s)
Humans , Antineoplastic Agents , Pharmacology , Apoptosis , Carcinoma, Non-Small-Cell Lung , Pathology , Cell Line, Tumor , Cell Proliferation , Cyclin-Dependent Kinase Inhibitor p21 , Metabolism , Hydroxamic Acids , Pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Pharmacology , Poly(ADP-ribose) Polymerases , MetabolismABSTRACT
Objective To investigate the relationship between changes of cholinergic system and memory ability impairment in rats long-term exposed to hypoxia-hypercapnia.Methods Forty-eight SD rats were randomly divided into control group,2 weeks hypoxia-hypercapnia group and 4 weeks hypoxiahypercapnia group.The chronic hypoxia-hypercapnia rat model was set up.The memory ability was assessed by eight-arm radial maze.Morphological changes were observed by the HE staining and Nissl staining.Acetylcholine(ACh) content,choline acetyl-transferase (ChAT) activity and acetyl-cholinesterase (AChE) activity in the hippocampus were detected by spectrophotometry,while expression of α7 neuronal nicotinic acetylcholine receptor (α7 nAChR) protein by Western blot.Results Memory ability,especially the working memory was impaired in rats exposed to chronic hypoxia-hypercapnia.And the memory ability decreased more markedly in four weeks group.Compared with those of normoxic rats,the levels of ACh and the activities of AChE and ChAT in the hippocampus of the two weeks group were significantly decreased (ACh:(58.9 ±2.7) vs (47.4 ±3.2) μg/mg (protein) ; AChE:(0.326 ±0.019) vs (0.247 ±0.020) U/mg (protein) ; ChAT:(127.1 ±8.6) vs (90.4 ±6.9) U/g (tissue wet weight),t =7.674,8.139,9.408,all P ＜ 0.05).Compared with the two weeks group,those changes were more obvious in the four weeks group rats (ACh:(47.4 ±3.2) vs (32.5 ±3.2) μg/mg (protein); AChE:(0.247 ±0.020),(0.170±0.019) U/mg (protein); ChAT:(90.4 ±6.9),(55.6 ±6.0) U/g (tissue wet weight),t =9.279,8.036,10.781,all P ＜ 0.05).Compared with the normoxic rats,the expressions of α7 nAChR protein were significantly decreased in two weeks group rats (t =4.481,P ＜ 0.05).Moreover,the expressions of α7 nAChR protein were significantly decreased in four weeks group rats comparing with the two weeks group (t =4.965,P ＜ 0.05).Conclusions An impairment of rat' s memory ability may be induced by hypoxia-hypercapnia,and the injury degree is correlated with the exposure time.Cholinergic system dysfunctions may contribute to the memory function defects in chronic hypoxia-hypercapnia rats.
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Objective To explore the changes of serum iron (SI)level and serum ferritin (SF) level in children with vasovagal syncope(VVS).Methods Twenty-one children [12 male,9 famel,8-14 years old,mean(11.71 ±2.31) years old] were enrolled in this study,who came from children syncope out-patient department or in-patient department of the Second Xiangya Hospital of Central South University from May 2011 to Apr.2012,complaining of syncope or pre-syncope symptoms and turned out to be head-up tilt testing(HUTF) positive,compared with 18 healthy children(healthy control group).All the children were taken blood in the early morning with empty stomach to measure blood SI,SF,hemoglobin(Hb),hematocrit value(Hct) and average red blood cell volume(MCV).The SPSS 16.0 software was used for statistical analysis.Results 1.Age and gender differences were found no statistical significance in syncope group and healthy control group(all P ＞ 0.05).2.SI level in syncope group was lower than that in healthy control group [(15.15 ± 4.55) μmol/L vs (18.24 ± 4.15) μmol/L,P ＜ 0.05].SF level in syncope group was lower than that in healthy control group [(59.10 ± 26.81) μg/L vs (79.83 ± 33.58) μg/L,P ＜ 0.05].Hct level in syncope group was higher than that in healthy control group [(40.19 ± 3.44) ％ vs (38.01 ± 2.68) ％,P ＜ 0.05].3.Gender compare in syncope group:there were no statistical difference in SI,SF,Hct,MCV and Hb between male and female vasovagal syncope patients(all P ＞ 0.05).4.There were no statistically significant differences in SI,SF,Hb,Hct and MCV between recurrent syncope and accidental syncope (all P ＞ 0.05).Conclusions SI,SF level reduce in VVS children,and there was no gender difference.
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A rapid analysis method of piperazine ferulate tablets by optic-fiber sensing technology with UV-vis absorption spectrum was established.Qualitative and quantitative data were obtained and compared by maximum and minimum wavelength,absorbance and contrast spectra.Similarity method was used to identify authenticity of drugs.The difference of contents measured by this method and UV determination method in China Pharmacopoeia showed no statistical significance (P＞0.05),while the similarity can be used as a parameter to identify the authenticity of drugs.