Objective To explore the effects and the mechanism of manumycin on KAT-18 cells Methods Human ATC (anaplastic thyroid cancer) KAT-18 cells were used. The cytotoxicity was analyzed by SRB assay. Apoptosis and cellular nitric oxide were detected by flow cytometry using annexin v and NO sensor dye. Superoxide anion was measured with a fluorescent plate reader by DHE.GSH was assayed by fluorescent Monochlorobimane. The SOD activities were assayed by colorimetric methods. The protein expression of Mn-SOD was determined by western blot. Results Manumycin decreased the viability of KAT-18 cells in a dose-dependent manner. Manumycin induced apoptosis significantly and NO generation simultaneously. Manumycin also induced superoxide anions generation. Manumycin reduced intracellular GSH in a time-course manner. However , manumycin did not decrease the SOD activity after 6 h treatment and Mn-SOD expression. A delayed induction of SOD activity was observed after 24 h manumycin treatment. N-acetyl-L-cysteine blocked NO and superoxide anions generation and apoptosis induction by Manumycin. Furthermore , NAC protected KAT-18 cells from the cytotoxicity of manumycin. Conclusion Manumycin induces apoptosis and has cytotoxic effects on KAT-18 cells. Cellular NO and superoxide anions generation are required for Manumycin-induced apoptosis in KAT-18 cells.

Objective To explore the effects of manumycin on U937 cells and its mechanisms.Methods Apoptosis was detected by flow cytometry using annexin V and propidium iodide (PI) after treatment with manumycin (2 μmol/L) for different time.The reactive oxygen species (ROS) was detected by flow cytometry using Reactive Oxygen Species Assay Kit.The expressions of PI3K,P-Akt and Akt were detected by Western blotting.Results Compared with the 0 h treatment,manumycin treatment resulted in apoptosis (P ＜ 0.05) and ROS generation (P ＜ 0.05) gradually in U937 cell lines.Furthermore,manumycin also inhibited the activation of phosphatidylinositol-3 kinase (PI3K)/Akt pathway.Moreover,NAC could decrease manumycin-induced ROS generation and inhibit the effects of manumycin on the PI3K/Akt pathway and protect U937 cells from apoptosis induced by manumycin.Conclusion Manumycin induces apoptosis in U937 human leukemia cells through the regulation of the PI3K/Akt pathway and ROS production plays a critical role in the progress.

Background and purpose: Recent literature has high lighted an important role of inflammation in promoting cancer. CRP (C reactive protein) is a way of building the bridge between inflammation and cancer. We aimed to explore correlations between CRP levels and clinical stages of nasopharyngeal carcinoma(NPC). Methods: We analyzed 108 cases, among which 68 cases were NPC, 20 cases were benign inflammatory diseases of nasopharynx, and another 20 were healthy volunteers as control. We detected the level of CRP using immunoturbidimetry (ITM), q test was calculated by SPSS. Results: The mean concentrations of CRP in NPC[(19.8±4.7) mg/L] were significantly increased compared to those in the control group[(6.2±1.8) mg/L], while they were significantly lower than those in benign inflammatory group[(45.6±7.9) mg/L]. In NPC, The mean concentrations of CRP in T4[(25.6±3.9) mg/L] were higher than those in T1[(17.4±5.8) mg/L], T2[(18.6±8.5) mg/L] and T3[(15.6±1.8) mg/L] respectively. The mean concentrations of CRP in N3[(28.0±7.1) mg/L] were higher than those in N0[(17.6±6.8) mg/L], N1[(21.3±5.1) mg/L] and N2[(18.6±5.6) mg/L] respectively. The mean concentrations of CRP in 1V[(25.7±5.5) mg/L] were higher than those in Ⅰ[(14.2±1.9) mg/L], Ⅱ[(16.1±3.9) mg/L] and Ⅲ[(23.0±7.7) mg/L] respectively (P<0.05). There were no statistic differences between the other groups. Conclusion: The serum CRP level is associated with the occurrence of NPC and benign inflammatory disease of nasopharynx. In NPC, the higher the CRP level is, the more advanced the TNM stage will be.

Objective:To investigate the expression of CD56 antigen in leukemia cells of the patients with acute myeloid leukemia (AML)and its relationship with the prognosis of AML, and to clarify the role of CD5 6 antigen expression in predicting the prognosis of the AML patients.Methods:171 AML (non-M3)patients aged from 14 to 60 years old,who received a IA Regimen as the first time inducing chemotherapy were chosen.Flow cytometric analysis was used to evaluate the CD56 expression in leukemia cells.COX proportional regression analysis was used to select the prognostic factors,and bivariable analysis was used to study the relationship between the positive rate of CD56 and overall survival (OS).The CD56+ group (n=52),including CD56≥50% expression group (n=39) and CD56<50% expression group (n=13),and CD56- group (n=119)were identified by the expression of CD56 antigen.The complete remission rate (CRR), the relapse rate, the median OS, the median disease-free survival (DFS)and the survival rate of patients were compared.Results:The medium OS of the patients in CD56+ group (14.2 months)was shorter than that in CD56- group (39.4 months)(P<0.05).Moreover,the medium OS in CD56≥50% group was shorter than that in CD56<50% group (11.7 months vs 20.3 months,P<0.05).The 1-year and 2-year survival rates of the patients in CD56+ group (61.5%,46.2%)were lower than those in CD56-group (75.6%,63.9%)(P<0.05).The 1-year survival rate had no significant difference between CD56≥50%group and CD56<50% group (53.8%vs 84.6%,P>0.05),while the 2-year survival rate in CD56≥50% group was lower than that in CD56<50% group (41.0%vs 61.5%,P<0.05).There were no significant differences of the CRR between CD56+ group (76.9%)and CD56- group (68.9%)as well as CD56≥50% group (58.9%)and CD56<50% group (63.5%)(P>0.05).The relapse rate and first year relapse rate of patients in CD56+ group (64.3% and 37.5%)were significantly higher than those in CD56- group (34.3% and 17.9% )(P<0.05). However,there were no significant differences of the relapse rate and first year relapse rate between CD56≥50%group (75.0% and 42.9%)and CD56<50% group (37.5% and 16.7%)(P>0.05).The DFS in CD56+ group was shorter than that in CD56- group (P<0.05).The same DFS result was also found between CD56≥50%group and CD56<50% group (P<0.05).Conclusion:The expression of CD56 antigen in leukemia cells predicts a bad prognosis in the AML patients,and the higher expression of CD56 indicates the worse prognosis.

Nasopharyngeal carcinoma is one of the most common malignant tumors in the southern part of China. The main etiologi-cal factors of nasopharyngeal carcinoma include genetic susceptibility, dietary factors, and Epstein-Barr virus (EBV) infection. EBV de-oxyribonucleic acid (EBV DNA) can be persistently detected in the plasma of patients with nasopharyngeal carcinoma, and its levels correlate with the disease stage. After successful treatment, EBV DNA is rapidly cleared from the plasma of patients;however, signifi-cant increases in plasma EBV DNA levels are observed in patients with recurrent or metastatic diseases after treatment. Accumulating evidence suggests that EBV DNA detection is useful in the early diagnosis and screening, diagnosis of tumor recurrence or distant me-tastasis, prognosis, and tailored treatment of patients with nasopharyngeal carcinoma. This review summarizes the aforementioned progresses to provide a basis for future clinical and research efforts.

Objective To explore the feasibility of 3D printed individualized applicator for the intracavitary HDR-brachytherapy for nasopharyngeal carcinoma.Methods CT scan was performed in 1 case of recurrent rT1 nasopharyngeal carcinoma and 1 case of T2 residual nasopharyngeal carcinoma and the obtained images were transmitted to 3D image processing software.The geometric contour parameters of the nasopharyngeal cavity were obtained and a pipeline was designed to make it close to the recurrent gross tumor volume (rGTV).Individualized cavity applicators were created by using 3D printer.The applicator was inserted into the patient's nasopharyngeal cavity through oral cavity.The source tube and false source were inserted into the preset pipe of the applicator.CT scan was performed again and the images were transmitted to the 3D brachytherapy planning system.Mter delineating the target volume and organ at risk,treatment plan was optimized.After completing the first treatment,the applicator was removed.Before second treatment in a few days,CT scan was reviewed to confirm whether the position was correct.Results When the applicator was inserted into the nasopharyngeal cavity,it could be fully aligned with the nasopharyngeal wall and self-fixed without additional fixation measures.Comparing the location of false source in multiple reviews of CT scan,the error was ≤ 1 mm.No significant discomfort was reported throughout the treatment.In optimized three-dimensional treatment,100％ prescription dose curve included the full rGTV,maximum dose of the brain stem and spinal cord was＜30％ prescription dose.Recurrent patients were given with a prescription dose of DT 40Gy/8 fractions/4 weeks and patients with residual tumors were given with 12Gy/2 fractions/1 week.No tumor recurrence was observed at postoperative 3 months in two cases.Conclusions The 3D printed individualized nasopharyngeal intracavitary applicator has the advantages of self-fixation,accurate location,good repeatability and good patient tolerance.The short-term outcome is effective,whereas its long-term clinical effect and adverse reactions need to be further observed.

OBJECTIVE Insomnia is the most fre-quent sleep disorder worldwide and the clinical applica-tion of therapeutic drugs has various adverse effects.In recent years,drugs developed from natural herbs have become potential alternative therapies for insomnia.Nuciferine,one of the main bioactive components obtained from the lotus leaves,has been reported to possess extensive pharmacological activities.However,its hypnotic and sleep regulatory effects have rarely been reported.Hence,this study was intended to investigate the pharma-cological effects of nuciferine and its mechanisms of action in insomnia.METHODS The hypnotic and seda-tive effects of nuciferine were investigated using the eval-uation of locomotor activity test and pentobarbital-induced sleep test in normal and serotonin(5-HT)depletion-induced insomniac mice.Furthermore,the sleep regulatory effects,including sleep time,sleep architecture,and δ-wave power spectral density,were explored using elec-troencephalography/electromyogram(EEG/EMG)-based sleep profiling in normal rats.Finally,the mechanisms of the hypnotic and sedative effects of nuciferine were explored usingin vivoand in silico experiments.RESULTS Nuciferine reduced locomotor activity and prolonged pen-tobarbital-induced sleep time in a dose-dependent man-ner in normal and insomniac model mice.Nuciferine sig-nificantly increased the total sleep time and non-rapid eye movement(NREM)sleep time,inhibited NREM sleep fragmentation,and improved delta power between 0.5 Hz and 1 Hz in normal rats.The results of molecular experiments showed that nuciferine could increase the 5-HT content and 5-HT1A receptor level in the hypothala-mus of insomnia model mice.CONCLUSION This study combined network pharmacological prediction and experi-mental pharmacological techniques to discover the seda-tive-hypnotic effect of nuciferine for the first time Nucif-erine can ameliorate sleep disorder in mice with insom-nia,possibly via serotonergic system.Nuciferine may rep-resent a novel treatment that alleviate the insomnia-like symptoms by modulating 5-HT system.