OBJECTIVETo summarize long-term outcomes of childhood lymphoblastic lymphoma (LBL) with protocol CCCG-97 and -2002.

METHODSFrom November 1998 to October 2010, 70 consecutive newly diagnosed childhood LBL (5 B-LBL and 65 T-LBL) were enrolled in this study, in which 22 received CCCG-97 and 48 CCCG-2002 protocols. St.Jude staging system was adopted. Patients were divided into three risk groups based on clinical stage and serum LDH, and received chemotherapy with different intensity. The factors, which were possibly associated with the prognosis, were analyzed. The survival rates were evaluated by Kaplan-Meier analysis.

RESULTSThe patients were 1.5 to 14 years old with the median age of 8 years old. They were evaluated as stage I-II for 6 , stage III41, and stage IV23 (15 were BM positive and 8 multiple bone metastases). Until Dec.31th, 2011,the mean follow-up was 62.5 months (range, 14 to 161 months) with the median follow-up of 48 months. 1-year overall survival (OS) was 74.3%, and 5- year event-free survival (EFS) 64.1% (abundance as event). Thirteen patients were complicated with serious condition during chemotherapy and 1 died of complication. Univariate analysis indicated that delayed and/or non-completed response on days 33 and 63 of induction was the unfavorable prognostic factor.

CONCLUSIONPrimary LBL usually located in the mediastinum. 90% of the patients was at advanced stage III-IV at first presentation. The 5-year EFS was 64.1%. Patients not achieved CR at days 33 and 63 at the end of induction was a poor prognostic factor.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; drug therapy ; Prognosis ; Prospective Studies ; Treatment Outcome

OBJECTIVETo explore the effect of Wnt signaling suppression on proliferation of non small cell lung cancer to gefitinib, and its related mechanisms.

METHODSPC9 and PC9/AB2 cells of both gefitinib sensitive and resistant were treated with different concentrations of gefitinib, and the proliferation index was measured using CCK8 kit. The members of Wnt signaling pathway were detected by Western blot. Dual luciferase reportor gene assay (TOP Flash) was used to document the transcriptional level of β-catenin. β-catenin siRNA was transfected into PC9/AB2 cells to suppress the Wnt signaling transcription, followed by treatment with different concentrations of gefitinib. Western blot was then used to detect the expression of EGFR and its downstream signaling after inhibit the expression of β-catenin.

RESULTSTreating with different concentrations of gefitinib, the resistance of PC9/AB2 cells to gefitinib was significantly increased (P < 0.05). The members of Wnt signaling expressed at higher level in PC9/AB2 cells than in PC9 cells (t = 24.590, P = 0.000). TOP Flash examination showed that the endogenous transcriptional activity of Wnt signaling was higher in PC9/AB2 cell than that in PC9 cell (t = 4.983, P = 0.008). Compared with the negative control group, apoptotic rate and sensitivity to gefitinib significantly increased in interfered group (P < 0.05). The expression of p-ERK1/2 significantly decreased after Wnt signaling suppression, although other proteins showed no significant alterations.

CONCLUSIONSuppressing the activity of Wnt signaling can partly reverse the celluar resistance to gefitinib in non small cell lung cancer.

Antineoplastic Agents ; administration & dosage ; pharmacology ; Apoptosis ; Carcinoma, Non-Small-Cell Lung ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Dose-Response Relationship, Drug ; Drug Resistance, Neoplasm ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Mitogen-Activated Protein Kinase 1 ; metabolism ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Phosphorylation ; Quinazolines ; administration & dosage ; pharmacology ; Wnt Signaling Pathway ; drug effects ; beta Catenin ; metabolism

OBJECTIVETo assess the early therapeutic and cognitive effect of repetitive transcranial magnetic stimulation (rTMS) combined with antidepressant medication in treatment of first-episode patients with major depression.

METHODSSixty first-episode depressed inpatients aged 18-45 y, who met the DSM-IV clinical criteria for major depressive episode were randomly assigned to citalopram treatment (20 mg/d) in combination with a two-week period of either rTMS (study group)or sham procedure (control group) on left dorsal-lateral prefrontal cortex (10 Hz, 90% motor threshold). The Hamilton Depression Rating Scale (HAMD) was used to assess the severity of depression. The Wisconsin Card Sorting Test (WCST) and Continuous Performance Test (CPT) were used to assess cognitive function of depression.

RESULTThe response rate was significantly greater in the study group compared to the control group after treatment (57% compared with 29%,P<0.05). The HAMD scores significantly declined after treatment in two groups, and the study group showed lower scores compared to the control group after 2 weeks (P<0.01). Neuropsychological assessments showed that there was no significant difference between the two groups except for the significant improvement in the categories on WCST in study group compared to the baseline (P<0.05) and the control group (P<0.05)after 2 weeks treatment. No serious event occurred in the patients during the rTMS study.

CONCLUSION10 Hz rTMS enhances early effects of citalopram and improves cognitive function in first-episode major depressive patients.

Adolescent ; Adult ; Antidepressive Agents ; therapeutic use ; Citalopram ; therapeutic use ; Combined Modality Therapy ; Depressive Disorder, Major ; therapy ; Humans ; Middle Aged ; Transcranial Magnetic Stimulation ; Treatment Outcome ; Young Adult

This study was purposed to explore the relationship between asparagine synthetase (AsnS) mRNA expression level and the sensitivity of leukemic cell lines to L-asparaginase. The AsnS mRNA expression level in 8 cell lines (Jurkat, HL-60, U937, NB4, THP-1, Namalwa, Karpas299 and K562) was determined by real-time quantitative PCR (RQ-PCR) based on fluorescence dye Eva Green before and after treatment with L-Asp, and the cell proliferation rates were analyzed by CCK-8 assay. The results showed that there was a significant disparity of AsnS expression level in 8 cell lines, and there were significant increases of AsnS expression level in cells co-cultured with L-Asp (p < 0.05). Of all these eight cell lines, cells sensitive to L-asparaginase had lower AsnS expression level and cells resistant to L-asparaginase had higher AsnS expression. U937 which was the most sensitive to L-asparaginase had the lowest AsnS expression level, while K562 was natural resistant to L-asparaginase and possessed of the highest AsnS level. It is concluded that the AsnS plays a critical role in regulating cellular biological behavior after depletion of asparagine, the AsnS mRNA expression level in cells reflects the sensitivity of cells to L-Asp. The results may imply the possibility for the use of L-asparaginase in leukemia with lower AsnS expression level.
Asparaginase ; metabolism ; pharmacology ; Aspartate-Ammonia Ligase ; metabolism ; Cell Line, Tumor ; Humans ; Leukemia ; enzymology

OBJECTIVETo study the antileukemic activity of L-asparaginase through determining the changes of 4 kinds of amino acids (Asn, Aspa, Glu and Gln) in cell culture medium.

METHODSFollowing L-Asp treatment with designed concentrations and duration, the IC50 (inhibitory concentration 50%) of 8 kinds of common leukemia cell lines (U937, HL-60, Jurkat, NB4, THP-1, Namalwa, Karpass299, K562) were determined by CCK-8 assay. The changes of the 4 kinds of amino acids mentioned above were detected by high performance liquid chromatography (HPLC).

RESULTSThe asparagines in cell culture medium were rapidly exhausted when treated with 0.01 U/mL L-Asp for 4 hrs or 1 U/mL L-Asp for 5 minutes. There were significant differences in the sensitivities to L-Asp of different leukemia cell lines. The sensitivities to L-Asp of various cell lines were dose-dependent. Low concentration of L-Asp resulted in a low IC50 and the IC50 increased following the L-Asp concentration increased.

CONCLUSIONSDifferent leukemia cell lines have different sensitivities to L-Asp, suggesting that exhaustion of asparagines around leukemia cells could not reflect the treatment efficacy of L-Asp. L-Asp antileukemic activity is dose-dependent, which suggests the importance of high-dose L-Asp on childhood acute lymphoblastic leukemia.

Asparaginase ; pharmacology ; Asparagine ; analysis ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Chromatography, High Pressure Liquid ; Humans ; Leukemia ; drug therapy ; metabolism ; pathology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy

OBJECTIVETo observe the effects of two different acupuncture treatment on cerebral blood flow velocity and early rehabilitation of hemiparalysis caused by cerebral infarction.

METHODSEighty patients were randomly divided into an alternate acupuncture group (n = 40) and a routine acupuncture group (n = 40). Both of the groups were treated with routine neurology medicine and application of good limb position combined with acupuncture. The patients in the alternate acupuncture group were treated by opposing needling and non-opposing needling, i. e. acupuncture at acupoints on both the healthy and affected sides alternately, twice each day, respectively. The routine acupuncture group was treated by acupuncture at the affected side, once daily. Scores of Scandinavian Stroke Scale (SSS) were evaluated before and after treatment in the two groups, and the mean blood flow velocity of middle cerebral artery (MCA) on the affected side was monitored during two different acupuncture treatment by using Transcranial Doppler (TCD).

RESULTSThe cured and markedly effective rate was 65.0% in the alternate acupuncture group and 37.5% in the routine acupuncture group with a significant difference between the two groups (P < 0.01). After treatment, the SSS score in the alternate acupuncture group was significantly lower than that in the routine acupuncture group (P < 0.01). The mean blood flow velocity of MCA during two different acupuncture treatment was both decreased significantly (both P < 0.05) and the mean blood flow velocity of MCA before the last treatment was decreased significantly in the alternate acupuncture group than those in the routine acupuncture group (P < 0.05).

CONCLUSIONThe therapeutic effect of the alternate acupuncture program for hemiparalysis caused by cerebral infarction is superior to that of the routine acupuncture program. It is suggested that the mechanism of acupuncture in treating hemiparalysis caused by cerebral infarction is to dilate cerebral blood vessels and improve cerebral perfusion.

Acupuncture Therapy ; Adult ; Aged ; Blood Flow Velocity ; Cerebral Arteries ; physiopathology ; Cerebral Infarction ; complications ; Hemiplegia ; physiopathology ; rehabilitation ; therapy ; Humans ; Male ; Middle Aged

OBJECTIVETo determine whether the high level of asparagine synthetase (AS) expression in childhood acute lymphocytic leukemia (ALL) is associated with an inferior prognosis.

METHODSAS mRNA level in leukemic cells from 53 newly diagnosed ALL children was measured by real time fluorescent quantitative PCR method. Patients were divided into groups according to their relapse risk and outcome, and the AS expression levels in each group were compared. The survival rates in different AS expressing level groups were estimated and compared.

RESULTSThe highest level of AS [median 17.25 (2.48-46. 82)] was observed in children failed remission, intermediate level [14.28 (3.20-54.47)] in relapsed children and the lowest level [5.08 (0.84-54.92)] in children with continuous complete remission (CCR) (P<0.05). The AS mRNA level [14.93 (2.48-54.47)] in children with poor outcome (un-remission and relapsed) was significantly higher than that in children in CCR (P<0.01). The two-year estimated disease free survival was much lower in children with high AS expression (53.8%) than in those with low AS expression (84.6%) (P<0.05).

CONCLUSIONHigh expression of AS is associated with a poor outcome in ALL children.

Adolescent ; Aspartate-Ammonia Ligase ; metabolism ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; enzymology ; Prognosis

Adult ; Diagnosis, Differential ; Humans ; Lung ; pathology ; Lung Diseases, Interstitial ; diagnosis ; drug therapy ; pathology ; Male ; Middle Aged

ObjectiveTo investigate and compare the behavioral changes, neuron loss of hippocampus and mossy fiber sprouting between pilocarpine-induced status epilepticus (SE) model and pentylenetetrazole (PTZ) kindling model in rats.MethodsAfter two different epilepsy models were made, Vedio was adopted to observe the behavioral changes. Nissl staining and Neo-timms' staining were separately used to observe and compare the neuron loss of hippocampus and mossy fiber sprouting in the dentate gyrus (DG) at different time points during epileptogenisis.ResultsNo recurrent spontaneous seizure, no neuron loss and no mossy fiber sprouting were found in PTZ kindling model; whereas obvious neuron loss was found in CA1, CA3 of hippocampus and hilus of DG, and mossy fiber sprouting were found in pilocarpine model in parallel with recurrent spontaneous seizures. ConclusionPTZ kindling model resembles absence epilepsy in human, while pilocarpine-induced status epilepticus model resembles chronic temporal epilepsy in human. Neuron loss and mossy fiber sprouting may play an important role in epileptogenisis. Pilocarpine-induced epilepsy model can be regarded as an ideal chronic temporal epilepsy model.

OBJECTIVETo study the optimum acupuncture treatment program and the mechanism for treatment of cerebral infarction.

METHODSSixty-three cases were randomly divided into 9 groups. The four factors, times of manipulation, the retaining time of the needle, acupuncture instrument and acupoints,and their corresponding three levels were adopted respectively in treatment of each group. Then nerve function defect score and insulin resistance were observed before and after treatment.

RESULTSThe acupoints, the times of manipulation and the retaining time of the needle have significant effects on nerve function defect and insulin resistance (P < 0.01 or P < 0.05), and the acupuncture instrument has a significant effect on insulin resistance (P < 0.01). The choice of acupoints was the most important factor for acupuncture treatment of cerebral infarction.

CONCLUSIONAcupuncture for regulating The Governor Vessel with twice manipulations and retaining the needle for 60 min is optimum treatment program for cerebral infarction. The good regulating effect of acupuncture on insulin resistance is one of the mechanisms of achieving the therapeutic results.

Acupuncture Points ; Acupuncture Therapy ; Cerebral Infarction ; Humans ; Insulin Resistance ; Needles