Animals ; Cell Culture Techniques ; Cells, Cultured ; Male ; Neural Stem Cells ; cytology ; Neurons ; cytology ; Olfactory Mucosa ; cytology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the detrimental effects of ouabain on cochlear spiral ganglion neurons (SGCs) in vivo and in vitro.

METHODSSeventy-five male SD rats were randomly divided into 5 groups. In addition to the normal control group, rats in other 4 groups received 0.01, 0.02, 0.05 mmol/L of Ouabain or saline through cochlear scala tympani drilling. Seven days after surgery, the hearing threshold was measured by distortion product otoacoustic emissions (DPOAE) and auditory brainstem response (ABR) in rats. In the in vitro study, SGNs were isolated from SD rats (E14) and treated with 1 × 10(-8) mmol/L of Ouabain. The damaged of SGCs were detected after ouabain treatment using immunohistochemistry, transmission electron microscope and scanning electron microscope in vitro.

RESULTSAfter administration of Ouabain, DPOAE did not change significantly. No significant difference in the amplitude of DPOAE could be observed among all the groups (P > 0.05). Compared with saline and normal control, ABR threshold was significantly increased in the Ouabain treated groups (P < 0.05), which correlated with the concentration of Ouabain. Electron microscopy showed that after treated with Ouabain, SGCs presented degenerative changes, including collapse of organelle structures, the karyotheca dissolved, myelin sheath disintegrating. Ouabain could damage type I SGCs but not type II SGNs.

CONCLUSIONSOuabain can damage SGCs, either in the in vivo or in vitro conditions.

Animals ; Cells, Cultured ; Cochlea ; cytology ; drug effects ; Male ; Ouabain ; toxicity ; Rats ; Rats, Sprague-Dawley ; Spiral Ganglion ; drug effects

OBJECTIVETo explore the clinical characteristics of adult acute lymphoblastic leukemia (ALL), compare the efficacy of different induction regimens and analyze the prognostic factors.

METHODSData of 149 adult ALL patients hospitalized in our institute between June 1998 and December 2005 were retrospectively reviewed. The results were analyzed with the SPSS11.5 software.

RESULTS1) Out of 133 patients available immunophenotype data, 118 (88.7%) were B-ALL and 15 (11.3%) T-ALL. Cytogenetic analysis was performed in 105 patients, 40 cases (38.1%) of them had a normal karyotype and 65 (61.9%) chromosome aberrations. 2) 149 patients completed the VDCP, VDLP or VDCLP induction therapies (at least 4 weeks treatment for each), 140 (93.7%) of them achieved complete remission (CR) with the first course CR rates of 80.8%, 92.3% and 81.4% , respectively (P=0.618). CR rates in patients after the induction regimens with or without asparaginase were 95.5% versus 92.1% (P=0.566). With a median follow-up of 14.5 (1-75) months, the median disease free survival (DFS) was 12 (1-74) months and median overall survival (OS) 17.5 (1-97) months. DFS of the three regimen groups at 3 and 5 years were 18.5% and 14.8%, 24.7% and 9.9%, 39.5% and 39.5%, respectively (P=0.0066). 3) COX regression analysis showed that the age (over 40 years), white blood cell (WBC) count ( > 40 x 10(9)/L) , t(9;22) (q34;q11)-positive and less than 4 courses consolidation chemotherapy were the unfavorable prognostic factors.

CONCLUSIONSMost adult ALL patients are B-ALL and karyotype have more changed. More than 90% patients can achieve CR with induction regimens consisting of 4 or 5 drugs. Induction regimens containing L-asparaginase may not affect the CR rate, but can improve DFS and OS. Age and WBC at diagnosis, presence of t(9;22) (q34;q11) and the courses of post-remission treatment are important prognostic factors.

Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Prognosis ; Retrospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVETo explore the mechanism of moxibustion arresting the pulmonary fibrosis and provide experimental basis for prevention and treatment of pulmonary fibrosis with acupuncture and moxibustion.

METHODSOne hundred and forty SD rats were randomly assigned to 4 groups: a blank group, a model group, a moxibustion group and a prednisone group, 35 rats in each group. The 3 groups expect the blank group were injected with bleomycin via trachea to induce experimental pulmonary fibrosis model, and 7 days after modeling, they were treated with moxibustion at bilateral Feishu (BL 13) and Gaohuang (BL 43), 3 cones each point, once each day, 10 days constituting one therapeutic course with an interval of one day between courses. After 3 courses, all rats were killed and expressions of TGF-beta1mRNA were detected with PCR method.

RESULTSThe content of TGF-beta1mRNA in the pulmonary tissue in the moxibustion group and the prednisone group was significantly lower than the model group (P < 0.01), and there was no significant difference between the moxibustion group and the prednisone group (P > 0. 05).

CONCLUSIONBoth moxibustion at Feishu (BL 13) and Gaohuang (BL 43), and prednisone treatment can significantly suppress the expression of TGF-beta1mRNA in the pulmonary tissue in the rat of bleomycin-induced pulmonary fibrosis.

Animals ; Bleomycin ; Humans ; Moxibustion ; Pulmonary Fibrosis ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; genetics

OBJECTIVETo analyze the complete remission (CR) rate, disease free survival (DFS) and overall survival (OS) of de novo acute myeloid leukemia (AML) patients treated with HA based three drugs induction chemotherapy and to explore the impact of cytogenetic abnormalities on the prognosis.

METHODSTwo hundred and forty-three untreated de novo AML patients were treated with HA based three drugs induction therapy. CR rate, DFS and OS were calculated. One hundred and eighty-four patients who had karyotype results were divided into four or three groups according to SWOG or MRC criteria respectively. Differences in CR rate, DFS and OS among different groups were evaluated.

RESULTSThe CR rate of all the 243 cases was 77.4%. The median DFS of the 188 CR patients was 28.5 (ranged from 1.0 to 153.0) months, DFS rates at 3 and 5 years were 45.4% and 40.2% respectively. The median OS of the 243 patients was 18.4 (range from 0.5 to 154.0) months. OS rates at 3 and 5 years were 36.9% and 31.4% respectively. According to SWOG criteria, CR rate, median DFS and OS were 97.8%, 87.4 months and 89.0 months for the favorable group; 81.9%, 17.6 months and 22.3 months for the intermediate group; 61.5%, 9 months and 11.5 months for the adverse group; and 79.3%, 29.0 months, 19.9 months for the unknown group, respectively. The differences among the four groups were statistically significant (P < 0.001). According to MRC criteria, CR rate, median DFS and OS were 96.1%, 79.9 months, 72.2 months for the favorable group; 80%, 17.6 months, 19.7 months for the intermediate group; and 43.8%, 16.5 months, 12 months for the adverse group, respectively. The differences among the three groups were statistically significant excepting for DFS between intermediate and adverse groups.

CONCLUSIONSHA based triple-drug induction regimens are highly effective in obtaining higher CR rate and longer survival time. Cytogenetics is the important prognostic factor for AML patients and SWOG karyotype subtyping criteria is more appropriate than that of MRC, the differences among the three groups being statistically significant.

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Cytarabine ; administration & dosage ; Disease-Free Survival ; Female ; Follow-Up Studies ; Harringtonines ; administration & dosage ; Humans ; Karyotyping ; Leukemia, Myeloid, Acute ; drug therapy ; genetics ; Male ; Middle Aged ; Prognosis ; Remission Induction ; Retrospective Studies ; Treatment Outcome

AIMTo investigate whether AcSDKP can inhibit proliferation and collagen synthesis in cultured rat cardiac fibroblasts mediated by PDGF.

METHODSNeonatal rat cardiac fibroblasts were isolated. The cell proliferation was observed by 3H-proline incorporation assay.

RESULTSOn the culture of 0.4% FBS, PDGF stimulated cardiac fibroblasts proliferation and collagen synthesis with a dose-dependent manner at the concentrations from 1 ng/ml to 20 ng/ml, in which 10 ng/ml PDGF reached its peak. AcSDKP at the concentration from 10(-10) mol/L to 10(-8) mol/L could inhibit cardiac fibroblasts proliferation and collagen synthesis mediated by PDGF. 10(-9) mol/L AcSDKP attained its peak on inhibiting cardiac fibroblasts proliferation and collagen synthesis.

CONCLUSIONAcSDKP can inhibit proliferation and collagen synthesis in cultured rat cardiac fibroblasts mediated by PDGF.

Animals ; Cell Proliferation ; Cells, Cultured ; Collagen ; biosynthesis ; Fibroblasts ; cytology ; drug effects ; metabolism ; Myoblasts, Cardiac ; cytology ; drug effects ; metabolism ; Oligopeptides ; pharmacology ; Platelet-Derived Growth Factor ; pharmacology ; Rats ; Rats, Wistar

Objective: To evaluate the prognostic value of (18)F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) in patients with diffuse large B cell lymphoma (DLBCL) undergoing autologous hematopoietic stem cell transplantation (auto-HSCT). Methods: Forty-eight patients with DLBCL treated at Peking University Cancer Hospital between November 2010 and December 2014 were assessed. All patients underwent PET/CT scanning prior to or after auto-HSCT. Correlation analysis was done based upon patients characteristics, PET/CT scan results and survival. Results: ①Among 48 patients, 27 was male, 21 female, median age was 43 (17-59) years old. ② Patients with negative pre-auto-HSCT PET/CT assessment demonstrated significantly better 3-year progression free survival (PFS) (87.1% vs 53.3%, χ(2)=7.02, P=0.019) and overall survival (OS) (90.3% vs 60.0%, χ(2)=6.51,P=0.022) than patients with positive pre-auto-HSCT PET/CT assessment. Three-year PFS (94.1% vs 30.0%, χ(2)=22.75, P=0.001) and OS (97.1% vs 40.0%, χ(2)=21.09, P=0.002) were also significantly different between patients with negative and positive post-auto-HSCT PET/CT assessment. ③ Multivariate analysis indicated a significant association of PFS (HR=13.176, P=0.005) and OS (HR=20.221, P=0.007) with post-auto-HSCT PET/CT assessment. Number of prior treatment regimens was associated with PFS (HR=10.039, P=0.040). ④ Harrell's C index revealed that the value of combined use of number of prior treatment regimens and post-auto-HSCT PET/CT assessment was superior to either one used alone in PFS (Harrell's C values were 0.976, 0.869 and 0.927 in combined use, number of prior treatment regimens and post-auto-HSCT PET/CT assessment, respectively), and the combined use of ECOG performance status and post-auto-HSCT PET/CT assessment significantly increased the Harrell's C index in OS (Harrell's C values were 0.973, 0.711 and 0.919 in combined use, ECOG performance status and post-auto-HSCT PET/CT assessment, respectively). Conclusions: Post-auto-HSCT PET/CT assessment is the main predictor of outcomes in DLBCL patients receiving auto-HSCT. Combined use of post-auto-HSCT PET/CT assessment and number of prior treatment regimens and ECOG performance status is a better prognostic tool in patients with DLBCL undergoing transplantation.
Adolescent ; Adult ; Disease-Free Survival ; Female ; Fluorodeoxyglucose F18 ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma, Large B-Cell, Diffuse ; Male ; Middle Aged ; Positron Emission Tomography Computed Tomography ; Prognosis ; Retrospective Studies ; Transplantation, Autologous ; Young Adult

OBJECTIVETo investigate the role of AcSDKP on collagen synthesis and degradation in cultured rat cardiac fibroblasts.

METHODSNeonatal rat cardiac fibroblasts were isolated and stimulated by PDGF. The cell proliferation was observed by (3)H-TdR incorporation assay. The synthesis of collagen was measured by (3)H-proline incorporation assay. The expression of type I and type III collagen and MMP-1 protein were measured by Western blot. The MMP-2 and MMP-9 activity was evaluated with zymography assay.

RESULTSPDGF stimulated cardiac fibroblasts proliferation with increased collagen synthesis and type I and type III collagen protein expressions as well as MMP-2 and MMP-9 activities and MMP-1 expression. AcSDKP inhibited cardiac fibroblasts proliferation induced by PDGF and reduced collagen synthesis and type I and type III collagen protein expression. AcSDKP also further up-regulated MMP-2 and MMP-9 activities and MMP-1 expression in cardiac fibroblasts induced by PDGF.

CONCLUSIONAcSDKP inhibited proliferation and collagen synthesis and up-regulated matrix metalloproteinases activity or expression induced by PDGF, which was possibly related with the effect of AcSDKP anti-fibrosis.

Animals ; Cell Proliferation ; drug effects ; Cells, Cultured ; Collagen ; biosynthesis ; Fibroblasts ; drug effects ; metabolism ; Matrix Metalloproteinase 2 ; biosynthesis ; Matrix Metalloproteinase 9 ; biosynthesis ; Myocytes, Cardiac ; drug effects ; metabolism ; Oligopeptides ; physiology ; Platelet-Derived Growth Factor ; drug effects ; Rats ; Rats, Wistar

Objective: To evaluate the clinical characteristics and survival outcomes of patients with de novo grade 3 or transformed follicular lymphoma (FL). Methods: Fifty-two patients treated at Peking University Cancer Hospital between January 2009 and September 2017 were assessed, including 28 patients with FL 3A grade, 13 patients with FL 3B grade, 11 patients with transformed FL. Baseline characteristics, survival and prognostic factors were analyzed. Results: ① Twenty-six male and 26 female patients were enrolled, including 28 patients with FL 3A grade, 13 patients with FL 3B grade, 11 patients with transformed FL. ②The 3-year progression-free survival (PFS) and overall survival (OS) for the entire cohort were 56.0% and 80.6%, respectively. Patients with international prognostic index (IPI) score 0-1 demonstrated significantly better 3-year PFS (80.3% vs 20.1%; t=18.902, P<0.001) and OS (95.7% vs 57.0%; t=10.406, P<0.001) than patients with IPI score 2-3. Three-year PFS (94.1% vs 37.2% vs 25.2%; P=0.002) and OS (100.0% vs 76.0% vs 59.8%; P=0.020) were also significantly different among patients with FLIPI 1 score 0-1, 2, ≥3. FLIPI 2 score was also identified as a prognostic factor for 3-year PFS (68.4%, 0, 0; P=0.001) and OS(87.5%, 76.2%, 0; P=0.003). ③Multivariate analysis indicated a significant association of PFS (HR=3.536, P=0.015) and OS (HR=15.713, P=0.015) with IPI. FLIPI 2 was associated with OS (score 0-1, HR=0.078, P=0.007; score 2, HR=0.080, P=0.022). Conclusion: De novo grade 3 or transformed FL might be a group of curable disease with current treatment strategies. IPI is still a prognostic tool in this scenario.
Disease-Free Survival ; Female ; Humans ; Lymphoma, Follicular ; Male ; Neoplasm Recurrence, Local ; Prognosis ; Retrospective Studies ; Survival Analysis

OBJECTIVE: To evaluate the involvement of different CD4 T cell subtypes in the anti-asthmatic effects of acupuncture in asthmatic mice. METHODS: BALB/c mice were challenged by ovalbumin (OVA) for the establishment of experimental asthma model. Mice were divided into 4 groups by a random number table including the normal control, asthma model, acupuncture and sham acupuncture groups (14 per group). Acupoints Dazhui (GV 14), bilateral Fengmen (BL 12) and Feishu (BL 13) were selected for manual acupuncture treatment every other day for 4 weeks and Huantiao (GB 30) was selected for sham acupuncture. Airway hyperresponsiveness was examined by Buxco Pulmonary System. Pulmonary histopathology analysis was performed for inflammatory cell infiltration and mucus hypersecretion by haematoxylin eosin staining and periodic acid-Schiffstaining. Inflammatory mediators assays of serum were investigated by enzyme-linked immunosorbent assay and Bio-Plex. CD4 T cell subpopulations including the expression levels of important factors in T lymphocyte polarization in lung tissue were examined by flow cytometric and Western blot analyses. Related pathways were detected by Western blot assay. RESULTS: Compared with the OVA-induced asthma model group, acupuncture could attenuate airway hyperresponsiveness, inhibit inflammatory cell infiltration and mucus hypersecretion (P<0.05 or P<0.01). Furthermore, acupuncture increased the expressions of T-bet and Foxp3, the cell numbers of CD4 interferon gamma (IFN-γ) and CD4 Foxp3 in lung tissue and the level of Treg type cytokine interleukin (IL)-10 in serum (P<0.05 or P<0.01). Meanwhile, acupuncture reduced the RAR-related orphan receptor gamma t (RORγt) level, the cell numbers of CD4 IL-17A as well as the levels of IL-5, IL-13 and IL-17A in serum (P<0.05 or P<0.01). In addition, both acupuncture and sham acupuncture could inhibit the phosphorylation of p38 and p44/42 (P<0.01). CONCLUSION Acupuncture could alleviate allergic airway inflammation by strengthening the activities of Th1 and Treg, thus regulating the balance of CD4 T cell subtypes in experimental asthmatic mice.