OBJECTIVETo explore the antitumoral effect of indirubin on androgen-independent prostate cancer PC-3 cells and its possible mechanisms.

METHODSWe measured the inhibitory effect of indirubin on the proliferation of prostate cancer PC-3 cells using MTT assay, detected their cell cycles by flow cytometry, and determined the expressions of the cell cycle regulatory protein cyclin D1 and its related downstream gene c-myc by Western blot.

RESULTSThe viability of the PC-3 cells was significantly decreased by indirubin in a concentration-dependent manner, reduced to 52. 2% and 13. 6% at 5 and 10 µmol/L, respectively. The cell cycle of the PC-3 cells was markedly inhibited by indirubin at 5 µmol/L, with the cells remarkably increased in the G0 and G1 phases and decreased in the S and G2/M phases. Meanwhile, indirubin also inhibited the expressions of cyclin D1 and c-myc in the Wnt signaling pathway.

CONCLUSIONIndirubin can suppress the proliferation of androgen-independent prostate cancer PC-3 cells, which may be associated with its inhibitory effect on the cell cycle and Wnt signaling pathway.

Antibiotics, Antineoplastic ; administration & dosage ; pharmacology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Coloring Agents ; Cyclin D1 ; metabolism ; Dose-Response Relationship, Drug ; Genes, myc ; Humans ; Indoles ; administration & dosage ; pharmacology ; Male ; Prostatic Neoplasms, Castration-Resistant ; drug therapy ; pathology ; Proto-Oncogene Proteins c-myc ; metabolism ; Tetrazolium Salts ; Thiazoles

0.05).The effective rates of patients with recurrence or metastasis were respectively 92%(12/13) and 7/9.The rate of acute radiation reaction of the rectum between the treatment group and control group were respectively 46%(13/28)and 80%(24/30),with a significant difference(P0.05),while the rate of severe bone marrow depression between two groups showed a significant difference(0 and 13%,P 0.05).Conclusion The therapeutic effect of 3DCRT is similar to that of traditional radiotherapy in the treatment of cervical carcinoma,but the former treatment method has a lower rate of acute complications.

BACKGROUND: Thyroid cancer stem cells are essential to the recurrence and metastasis of thyroid carcinoma. Leukemia inhibitory factor receptor (LIFR) shows a downward trend in a variety of malignant tumors, and its overexpression can inhibit the recurrence and metastasis of malignant tumors. OBJECTIVE:To explore the effect of LIFR on the stemness maintenance and lung metastasis of thyroid cancer stem cells in vivo. METHODS: Primary thyroid cancer cells TCLM were isolated from the lung metastases of a metastatic thyroid cancer patient. Serum-free suspension culture was used to form tumor cell balls. Flow cytometry was used to screen CD133+phenotype of metastatic thyroid cancer stem cell subpopulation TCLM-S. The overexpressed recombinant lentiviral plasmid containing LIFR and its negative control containing the empty plasmid were infected into thyroid cancer stem cells TCLM-S at the ratio of virus/cell number=20, and screened with 2.0 mg/L puromycin to construct TCLM-SLIFRand TCLM-Scontrolstem cells which stably expressed LIFR and its control. Real-time quantitative PCR (qRT-PCR) was used to detect the expression of LIFR in TCLM-SLIFRand TCLM-Scontrolstem cells. Flow cytometry was used to detect the percentage of CD133+phenotype cell subsets, western blot assay was used to detect the expression of tumor stemness related factors SOX2, Oct4, Nanog and tumor invasion and metastasis related proteins E-cadherin, matrix metalloproteinase (MMP)-2, MMP-7 in TCLM-SLIFRand TCLM-Scontrol stem cells. TCLM-SLIFRand TCLM-Scontrolstem cells were respectively injected into BALB/c nude mice by tail vein, and the lung metastasis model of thyroid cancer stem cells was constructed. The effect of LIFR overexpression on lung metastasis was observed. RESULTS AND CONCLUSION: Compared with TCLM-Scontrolcells, the expression of LIFR in TCLM-SLIFRcells was significantly increased, the proportion of CD133+phenotype stem cell subsets was significantly decreased, the expression of SOX2, Oct4 and Nanog were significantly decreased, the expression of E-cadherin was significantly increased, and the expression of MMP-2 and MMP-7 was significantly decreased. Moreover, the number of lung metastasis in nude mice given TCLM-SLIFRcells was significantly decreased as compared with those given TCLM-Scontrol cells.To conclude,LIFR overexpression can decrease the stemness and ability of lung metastasis in vivo.

Objective To study the efficacy of late course accelerated fractionation(LCAF) radio- therapy in the treatment of nasopharyngeal carcinoma(NPC).The end-po s were local control,radiation-in- duced complications,factors influencing survival.Methods From December 1995 to April 1998,178 NPC patients were admitted for radiation treatment.The radiation beam used was ~(60)Co?or 6 MV X-ray.For the first two-thirds of the treatment,two daily fractions of 1.2 Gy were given to the primary lesion ,with an interval of≥6 hours,5 days per week to a total dose of 48 Gy/40 fractions,over a period of 4 weeks.For the last one third of the treatment,i.e.beginning from the 5th week,an accelerated hyperfractionation schedule was carried out.The dose per fraction was increased to 1.5 Gy,2 fractions per day with an interval of≥6 hours,the total dose for this part of the protocol was 30 Gy/20 fractions over 2 weeks.Thus the total dose was 78 Gy in 60 fractions in 6 weeks.Results All patients completed the treatment.Acute mucosi- tis:none in 2 patients,Grade 1 in 43,Grade 2 in 78,Grade 3 in 52,and Grade 4 in 3 patients.Local control rate:the 5-year nasopharyngeal local control rate was 87.7%,and the cervical lymph node local control rate was 85.7%.The 5-year distant metastasis rate was 26.1%,and 5-year survivals was 67.9%. Sixteen patients had radiation-induced cranial nerve palsy.Conclusions With this treatment schedule, patient's tolerance is good,local control and 5 year survivals are better than control groups of conventional fractionation and hyperfractionation radiotherapy.Radiation-related late complication does not increase.Ran- domized clinical trials are being carried out to further confirm the efficacy of LCAF for nasopharyngeal carci- noma.

OBJECTIVEThe aim of the study was to review the cases of Kawasaki Disease (KD) and analyze the clinical features especially their cardiac complications.

METHODSTotally 283 patients with KD were hospitalized from 1992 to 2002. Their clinical features and factors associated with increased risk of coronary artery aneurysms were reviewed.

RESULTS(1) Among the 283 KD patients, 186 were male and 97 were female. The male-female ratio was 1.9:1. Most of them (71%) were younger than 3 years old. Seasonal peak was in spring and summer (from May to Aug). Depending on the criteria of KD, 228 (81%) were diagnosed as typical KD and 55 (19.4%) were atypical KD. All patients had fever, lasting for 6.1 days. The most common clinical features were oral mucosal changes (97.5%) and cervical lymphadenopathy (95.4%), conjunctivitis (91.2%). And changes in the extremities (89.8%) and rash (81.5%) were also noted. (2) Before the treatment, coronary artery abnormalities were seen in 103/279 (36.9%), which occurred within 4 - 30 days of fever onset. Two weeks after intravenous gamma globulin (IVIG) treatment, the new cases of coronary artery abnormalities were 28/211 (13.3%). The prevalence of coronary artery aneurysms (CAA) with KD was 4.7%. The risk factors of CAA were male cases (P < 0.05) and fever lasting longer than 9 days (P < 0.05). Other cardiac abnormalities in acute phase included left atrial and ventricular enlargement (40/279, 14.3%) and changes in ECG (57/274, 20.8%). The pericardial effusions were found in 11 cases (3.9%).

CONCLUSIONSCardiac complications of KD occurred in the early period of KD. The new cases of coronary artery abnormalities were 13.3% after IVIG treatment. The risk factors of CAA included male cases and fever lasting for longer time.

Child, Preschool ; Coronary Aneurysm ; epidemiology ; etiology ; Female ; Heart Diseases ; diagnosis ; etiology ; Humans ; Immunoglobulins, Intravenous ; administration & dosage ; Male ; Mucocutaneous Lymph Node Syndrome ; complications ; diagnosis ; drug therapy ; Prevalence ; Risk Factors

Abdominal Wall ; Adenocarcinoma ; diagnosis ; Colonic Neoplasms ; diagnosis ; Female ; Histiocytoma, Malignant Fibrous ; diagnosis ; Humans ; Ileal Neoplasms ; diagnosis ; Ileocecal Valve ; Leiomyoma ; diagnosis ; Middle Aged ; Neoplasms, Multiple Primary ; diagnosis ; Soft Tissue Neoplasms ; diagnosis ; Uterine Neoplasms ; diagnosis

Objective To study the effect of intestinal flora on the pharmacokinetics of ticagrelor in rats.Methods A total of 45 SD rats were randomly divided into control group,test A group and test B group.Rats of test groups were orally given live combined bifidobacterium and lactobacillus tablets for 7 days,respectively;rats of control group were given the same volume distilled water.On day 8,ticagrelor was orally administered to all rats.Blood samples were obtained at 0.08,0.25,0.50,1,1.5,2,3,4,6,8,12,24 h after ticagrelor administration.The plasma concentration of ticagrelor was determined by LC-MS/MS.The pharmacokinetic parameters were determined by DAS 2.1.1 software and the statistic analysis was processed with SPSS 21.0 software.Results The pharmacokinetic parameters of ticagrelor in the test A group,test B group and control group were as follows:AUC0-t were (6336.24 ± 1840.46),(4444.05± 1033.43) and (4469.32 ±928.47) ng· mL-1 · h-1;AUC0-∞ were (6841.98 ± 1975.95),(4656.66 ± 1083.78) and (4736.47 ± 897.42) ng · mL-1 · h;Cmax were (858.65 ± 275.98),648.81 ± 215.59) and (617.49 ± 168.95)ng · mL-1;t1/2 were (6.40 ± 2.18),(5.25 ± 1.39) and (5.68 ± 2.08) h;tmax were (0.88 ± 0.23),(0.90 ± 0.21) and (1.30 ± 0.59) h;clearance (CL) were (2.82±0.72) (4.07±0.99) and (3.95±0.91) L·h-1 ·kg-1;apparent volume of distribution (Ⅴ) were (26.07 ± 12.00),(31.45 ± 14.65) and (32.95 ± 14.17) L · kg-1.There were significant differences in AUC0-t,AUC0-∞,Cmax,tmax and CL between test A group and control group (P ＜ 0.05).On the contrary,no significant differences were observed on the pharmacokinetic parameters between test B group and control group.Conclusion Increased intestinal probiotics can increase the AUC0-t,AUC0-∞,and Cmax of ticagrelor,while decrease the CL of ticagrelor.

PURPOSE: This study aimed to investigate the effects of single-bout exercise on mitochondrial function, dynamics (fusion, fission), and mitophagy in cardiac and skeletal muscles. METHODS: Fischer 344 rats (4 months old) were randomly divided into the control (CON) or acute exercise (EX) group (n=10 each). The rats performed a single bout of treadmill exercise for 60 minutes. Mitochondrial function (e.g., O₂ respiration, H₂O₂ emission, Ca²⁺ retention capacity), mitochondrial fusion (e.g., Mfn1, Mfn2, Opa1), mitochondrial fission (e.g., Drp1, Fis1), and mitophagy (e.g., Parkin, Pink1, LC3II, Bnip3) were measured in permeabilized cardiac (e.g., left ventricle) and skeletal (e.g., soleus, white gastrocnemius) muscles. RESULTS: Mitochondrial O₂ respiration and Ca²⁺ retention capacity were significantly increased in all tissues of the EX group compared with the CON group. Mitochondrial H₂O₂ emissions showed tissue-specific results; the emissions showed no significant differences in the left ventricle or soleus (type I fibers) but was significantly increased in the white gastrocnemius (type II fibers) after acute exercise. Mitochondrial fusion and fission were not altered in any tissues of the EX group. Mitophagy showed tissue-specific differences: It was not changed in the left ventricle or white gastrocnemius, whereas Parkin and LC3II were significantly elevated in the soleus muscle. CONCLUSIONS A single bout of aerobic exercise may improve mitochondrial function (e.g., O₂ respiration and Ca²⁺ retention capacity) in the heart and skeletal muscles without changes in mitochondrial dynamics or mitophagy.

OBJECTIVETo observe the therapeutic effect of autologous cytokine-induced killer cells (CIK) on HBV DNA positive patients with liver cirrhosis.

METHODSHBV DNA positive 33 patients with cirrhosis were treated with CIK. Before and after cultured in vitro and post-treatment, CD3+, CD3+CD4+, CD3+CD8+, CD3+CD56+ cells, mDC and pDC were detected by flow cytometry. The indexes of virus and liver function were compared between pre- and post-treatment.

RESULTSCD3+, CD3+CD8+ cells and CD3+CD56+ cells were higher after cultured in vitro and after transfused back than those before culture (91.5 +/- 10.3, 74.4 +/- 9.9 vs. 67.9 +/- 12.8; 60.9 +/- 15.5, 37.3 +/- 15.1 vs. 27.9 +/- 10.9; 18.4 +/- 11.7, 14.5 +/- 7.5 vs. 10.6 +/- 7.1). The percentages of mDC and pDC also increased after-treatment vs. pre-treatment (0.54 +/- 0.18 vs. 0.70 +/- 0.29; 0.26 +/- 0.13 vs. 0.41 +/- 0.25). HBV DNA became undetectable in 12 patients and decrease exceeded 100 times in 4 patients after treatment. HBeAg became undetectable in 10 of 14 patients who were HBeAg positive pretreatment patients, among them 2 patients had HBeAb sero conversion. The liver function was improved after treatment. All patients tolerated the treatment.

CONCLUSIONCIK treatment can increase immune effector cells and has some antiviral effect and is safe.

Adoptive Transfer ; adverse effects ; methods ; Adult ; Aged ; Cells, Cultured ; Cytokine-Induced Killer Cells ; cytology ; immunology ; transplantation ; Fatigue ; etiology ; Female ; Headache ; etiology ; Hepatitis B ; complications ; virology ; Humans ; Liver Cirrhosis ; etiology ; immunology ; therapy ; Male ; Middle Aged ; Transplantation, Autologous ; Treatment Outcome

BACKGROUNDSeveral studies using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) have indicated that cognitive remediation therapy (CRT) might improve cognitive function by changing brain activations in patients with schizophrenia. However, the results were not consistent in these changed brain areas in different studies. The present activation likelihood estimation (ALE) meta-analysis was conducted to investigate whether cognitive function change was accompanied by the brain activation changes, and where the main areas most related to these changes were in schizophrenia patients after CRT. Analyses of whole-brain studies and whole-brain + region of interest (ROI) studies were compared to explore the effect of the different methodologies on the results.

METHODSA computerized systematic search was conducted to collect fMRI and PET studies on brain activation changes in schizophrenia patients from pre- to post-CRT. Nine studies using fMRI techniques were included in the meta-analysis. Ginger ALE 2.3.1 was used to perform meta-analysis across these imaging studies.

RESULTSThe main areas with increased brain activation were in frontal and parietal lobe, including left medial frontal gyrus, left inferior frontal gyrus, right middle frontal gyrus, right postcentral gyrus, and inferior parietal lobule in patients after CRT, yet no decreased brain activation was found. Although similar increased activation brain areas were identified in ALE with or without ROI studies, analysis including ROI studies had a higher ALE value.

CONCLUSIONSThe current findings suggest that CRT might improve the cognition of schizophrenia patients by increasing activations of the frontal and parietal lobe. In addition, it might provide more evidence to confirm results by including ROI studies in ALE meta-analysis.

Brain ; physiopathology ; Cognition ; Cognitive Remediation ; Humans ; Likelihood Functions ; Magnetic Resonance Imaging ; Positron-Emission Tomography ; Schizophrenia ; diagnostic imaging ; therapy