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While neuroblastoma accounts for 15% of childhood tumor-related deaths, treatments against neuroblastoma remain scarce and mainly consist of cytotoxic chemotherapeutic drugs. Currently, maintenance therapy of differentiation induction is the standard of care for neuroblastoma patients in clinical, especially high-risk patients. However, differentiation therapy is not used as a first-line treatment for neuroblastoma due to low efficacy, unclear mechanism, and few drug options. Through compound library screening, we accidently found the potential differentiation-inducing effect of AKT inhibitor Hu7691. The protein kinase B (AKT) pathway is an important signaling pathway for regulating tumorigenesis and neural differentiation, yet the relation between the AKT pathway and neuroblastoma differentiation remains unclear. Here, we reveal the anti-proliferation and neurogenesis effect of Hu7691 on multiple neuroblastoma cell lines. Further evidence including neurites outgrowth, cell cycle arrest, and differentiation mRNA marker clarified the differentiation-inducing effect of Hu7691. Meanwhile, with the introduction of other AKT inhibitors, it is now clear that multiple AKT inhibitors can induce neuroblastoma differentiation. Furthermore, silencing AKT was found to have the effect of inducing neuroblastoma differentiation. Finally, confirmation of the therapeutic effects of Hu7691 is dependent on inducing differentiation in vivo, suggesting that Hu7691 is a potential molecule against neuroblastoma. Through this study, we not only define the key role of AKT in the progression of neuroblastoma differentiation but also provide potential drugs and key targets for the application of differentiation therapies for neuroblastoma clinically.
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Objective:To understand the infection and distribution of syphilis in hospitalized patients, thus to provide reference for syphilis prevention and control.Methods:TP-ELISA test was used to examine early syphilis antibody, and adopted the TPPA test to validation syphilis antibody, and TRUST was used to determine the titer of syphilis antibody in 80 478 hospitalized patients from January 2015 to November 2017, then the results were retrospectively analyzed.Results:Among 80 478 inpatients, 1 326 cases were positive by TP-ELISA test(1 223 cases positive, 101 cases weak positive and 2 cases negative by TPPA confirmed). The positive rates of TP-ELISA in different years were 1.62%(445/27 394), 1.72%(490/28 412) and 1.58%(389/24 672), respectively, and the difference was not statistically significant( P>0.05). The positive rates of male and female patients were 2.02%(689/33 985) and 1.37%(635/46 479), and the difference was statistically significant(χ 2=52.91, P=0.00). The positive rates of ≤18 years old, >18-59 years old, >59-79 years old and>79 years old were 0.32%(7/2 161), 1.44%(765/53 001), 2.31%(488/21 163) and 1.50%(62/4 153), respectively.The highest proportion of syphilis patients was in the group of >59-79 years old, and the differences were statistically significant compared with the other groups(χ 2=37.08, 67.05, 10.80, all P<0.01). Among the TP-ELISA positive patients, 54.90%(728/1 326) had TRUST titer negative, 36.50%(484/1 326) had titer less than 1∶8, and the others had 8.44%(112/1 326). Conclusion:The incidence of syphilis was higher in males than in females in 80 478 hospitalized patients.The highest positive rate was found in >59-79 years old group, and the number of elderly cases increased rapidly.Therefore, the effective interventions should be developed to control the transmission of syphilis according to the epidemiological features.
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Objective To evaluate the changes of adenosine metabolism pathway related molecules and their contribution to inflammatory injury in primary biliary cholangitis (PBC).Methods The consecutive samples of 49 subjects with PBC from The First People's Hospital of Taicang and The Second People's Hospital of Changshu were recruited from October 2016 to October 2017,and 36 healthy controls were involved in this study.The expression of CD39 and CD73 on CD4+T cells and Foxp3 + regulatory T cells were assayed by flow cytometry and the concentration of adenosine triphosphate (ATP) in serum was analyzed by ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS).The correlations between Tregs,ATP and liver function were analyzed,i.e.,alanine aminotransferase (ALT),aspartate aminotransferase (AST),gamma-glutamyltransferase (GGT),alkaline phosphatase (ALP) and Mayo scores.Results In the patients with PBC,low proportions of CD4+CD39+T cells were noted compared with healthy controls [(5.28 ± 1.92) ％ vs (11.0l ± 3.19) ％,t =10.25,P ＜ 0.01].The patients with PBC also had significantly low proportion of CD4+CD25 + Foxp3+ CD39+ T cells compared with healthy controls [(23.75 ± 9.48) ％ vs (54.68 ± 5.18) ％,t =13.79,P ＜0.01].No significant difference of the proportion of CD4+CD73+T or CD4+CD25+ Foxp3+CD39+T cells was found between PBC and control groups (t values were 2.235 and 1.083,P ＞ 0.05).The level of serum ATP was higher in the patients with PBC than that of healthy controls [(200.28 ± 79.41) μg/L vs (89.20 ± 33.76) μg/L,t =8.367,P ＜ 0.01].A significant correlation was demonstrated between the proportion of CD39 + Treg in total Treg cells and the levels of ATP (r =-0.413,P =0.003),GGT (r=-0.378,P=0.007) and Mayo score (r=-0.382,P=0.007).Conclusion The low proportion of CD39+ Treg cells may contribute to the down-regulation of ATP hydrolysis in the patients with PBC.No significant change of CD73 + Treg cells was found in PBC patients.
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Objective To study the relationship between intrauterine infection and early neonatal sepsis.Method From October 2015 to September 2016,the clinical data of pregnant mothers and their newborns in Shenzhen Longhua District Central Hospital were collected,and data of Shenzhen People's Hospital from January 2016 to June 2016 were collected.100 pairs of pregnant mothers and their newborns with confirmed or suspected intrauterine infection were selected as the observation group,and another 100 pairs without intrauterine infection during the same period as the control group.The ratio of term infants vs.premature infants was 1∶ 1.The complete blood count (CBC),CD64,procalcitonin (PCT) and C-reactive protein (CRP) were measured in peripheral blood of all mothers on the day of delivery.The CBC,CD64,CRP,PCT,blood culture of both umbilical venous blood and peripheral blood in neonates were examined and the pathological examination of placenta was performed.Result The positive rate of placental pathology and umbilical cord blood culture in observation group were significantly higher than that in the control and the positive rate in preterms was higher than the terms in observation group (P ＜ 0.05).No significant differences existed between term and premature newborns on the positive rate of peripheral blood culture (P ＞ 0.05).The positive rate of blood culture from umbilical cord blood was higher than peripheral blood in observation group (P ＜ 0.05),but no significant difference in control group (P ＞ 0.05).The incidence of septicemia in term and premature newborns in observation group was significantly higher than the control group (P＜ 0.05).The CD64,PCT in mother's peripheral blood and umbilical cord blood,and CRP in mother's blood were all higher than the control group,the differences were statistically significant (P ＜ 0.05),but CRP in umbilical cord blood in both group were similar (P ＞ 0.05).The area under ROC curve of CD64 and PCT in mother's peripheral blood,CD64 and PCT in umbilical cord blood to diagnose early-onset septicemia in newborns was 0.755,0.793,0.852 and 0.811,respectively.Conclusion The risk of neonatal infections is significantly increased because of intrauterine infection.Combination of peripheral and umbilical blood cultures can increase the accuracy of sepsis diagnosis.Both CD64 and PCT in umbilical cord blood and maternal blood can be used as indicators of intrauterine infection with a predictive value in the diagnosis of early-onset neonatal sepsis.
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Objective To study the expression and significance of Neogenin,Hepcidin and serum ferritin(SF)in patients with cancer-related anemia.Methods To test the serum levels of Neogenin,Hepcidin and SF in 107 cases,including 55 cases with cancer-related anemia and 52 cases of non-anemia with tumor by ABC-ELISA.Results ①The serum levels of Neogenin in patients with cancer-related anemia were 0.77 ± 0.45 ng/ml,which were lower than 0.98 ± 0.60 ng/ml in non-anemia group (t=2.003 8,P 0.05).③In patients with cancer,there were positive correlation be-tween Neogenin and Hb (r=0.212 4,t=2.226 4,P 0.05).④There were positive cor-relation between Hepsidin and SF (r=0.486 6,P <0.01).Conclusion There were lower expression of Neogenin,higher ex-pression of Hepcidin in patients with cancer-related anemia is a complex process.The abnormal expression of Neogenin and Hepcidin which were lead to the loss of use of iron are the key factors attribute to anemia in patients with cancer.
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Objective To study the expression feature and clinical significance of plasma Protein C(PC) in pre‐PICC placement and post‐PICC placement in patients with cancer .Methods The levels in plasma of PC was tested by ELISA in patients with cancer in one day before PICC placement ,in one day ,30 day ,and 90 day after PICC placement ,the change of feature and clinical signifi‐cance was analyzed .Results The levels of PC in one day after PICC placement were 3 .74 ± 1 .99 μg/L ,the levels was lower than the levels of in one day before ,and in 30 ,90 day after PICC placement ,which were 5 .00 ± 2 .40 ,4 .78 ± 2 .41 and 5 .35 ± 2 .71 μg/L (q=3 .74 ,2 .85 and 4 .58 respectively ,P0 .05);There were no correlation both PC levels and D‐D levels ,and both PC levels and PLT count(r= -0 .024 1 and 0 .111 0 ,all P>0 .05) .Conclusion The PC levels in one day after PICC placement were lower ,but there were no correlation both PC and D‐D ,and PLT .PICC catheter were safety .
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Objective To study the relationship between serum erythropoietin(Epo)level and chemotherapy-induced hemoglobin(Hb)level in elderly patients with cancer. Methods One hundred senile patients(aged≥60 years)with cancer and one hundred and seventy non-senile patients(aged＜60 years)with cancer were selected as aged group and control group,respectively.The serum Epo level was detected by enzyme-linked immunosorbent assay(ELISA). Results (1)The average levels of the serum Epo in aged group and control group were(22.0±15.1)U/L and(30.4±21.8)U/L,respectively(t=1.2988,P＞0.05).A negative correlation was found between the levels of Epo and Hb in elder cancer patients(r=0.3700,P＜0.001).(2)The levels of serum Epo were(14.7±10.6)U/L,(20.2±9.0)U/L and(42.3±24.8)U/L in 55 cases with normal Hb level,22 cases with mild anemia and 23 cases with moderate to severe anemia,respectively(F=11.6886,P＜0.01).(3)The levels of Epo were(20.2±10.8)U/L,(45.2±39.1)U/L and(25.8±15.9)U/L before chemotherapy,after 4 treatment cycles and 2 treatment cycles respectively(F=4.5477,P＜0.01).The levels of Hb were(111.0±20.5)g/L,(96.8±16.6)g/L and(102.1±19.3)g/L before chemotherapy,after 4 treatment cycles and 2 treatment cycles respectively(F=4.0071,P＜0.01).Conelusions There is no statistical difference in serum Epo level between senile patients with cancer and non-senile patients with cancer.but serum Epo levelis higher in patients with anemia than without anemia.There is a negative correlation between the levels of Epo and Hb.Chemotherapy can decrease the level of Hb and increase the serum 1evel of Epo in part of patients.The changes are correlated with the conditions of patients before chemotherapy and the time of chemotherapy.
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Objective To study the expression and significance of B-cell activating factor(BAFF) and a proliferation-inducing ligand(APRIL) in patients with idiopathic thrombocytopenic purpur(ITP). Methods The serum levels of BAFF and APRIL in 27 cases with ITP were tested by ELISA.Results ①The serum levels of BAFF in ITP were higher than those of control group (3.92?1.88?g/ml vs 2.90?0.52?g/ml,P
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Objective To evaluate one-stage procedure for the treatment of neonatal intermediate and high imperforated anus. Methods Clinical data of 21 neonates with intermediate or high imperforated anus undergoing one-stage surgical procedure were summarized. Results Postoperative complication included mucous overlap and soiling in 1 case, and occasional soiling in 2 cases. No postoperative constipation developed in any case. Conclusions Neonatal one-stage procedure avoids short comings often seen in staged procedures and needs no colostomy, promoting hyperplasia and prolongs sphincter during early stage, preventing secondary megacolon.