Objective To investigate the effect of galangin on cardiac remodeling and cardiac func-tion after myocardial infarction(MI).Methods A total of 32 male C57/BL6 mice(8-10 weeks old)were subjected for MI modeling,and finally 24 mice were assigned into control group[sham operation+hydroxycellulose sodium(CMC-Na)],model group(MI+CMC-Na),and experimental group(MI+galangin),with 8 mice in each group.After MI modeling,the mice of the experimen-tal group were given 40 mg/kg galangin by gavage for 4 weeks,and those of the control group and the model group were given the same volume(0.4 ml)of CMC-Na solution.HE staining was used to observe the size of the infarct area.The mRNA levels of inflammatory factors in the heart were detected by qRT-PCR,and protein levels of related signaling pathway proteins were measured with Western blotting.Immunofluorescence(IF)assay was applied to detect the infiltration of in-flammatory cells in the infarct border zone.TUNEL staining was employed to detect cell apoptosis in the infarct border zone.Results At 4 weeks after modeling,larger infarct size,enhanced expression levels of IL-1β,IL-6,TNF-α,p-P65,p-IκBα and Bax,elevated apoptotic rate,decreased cardiac function indicators such as FS and LVEF,and reduced Bcl-2 expression level were observed in the model group than the control group(P＜0.05).The experimental group had sig-nificant smaller myocardial infarct size[(11.64±0.64)％vs(21.84±1.94)％],less CD3 positive T cells[(3.10±0.46)％vs(6.28±0.24)％],F4-80 positive macrophages[(1.98±0.50)％vs(5.35±0.62)％]and LY6G positive neutrophils[(6.33±0.67)％vs(11.33±1.77)％],decreased expression levels of IL-1β,IL-6,TNF-α,p-P65,p-IκBα and Bax,reduced apoptotic rate[(21.45± 1.62)％vs(35.68±0.88)％],and increased FS and LVEF values and Bcl-2 expression level when compared with the model group(P＜0.05).Conclusion Galangin improves myocardial remode-ling and cardiac dysfunction after MI by inhibiting inflammatory response and cell apoptosis.

Objective:To analyze the genetic mutations and clinical features of the subtypes of classical BCR-ABL-negative myeloproliferative neoplasm (MPN) .Methods:Mutations of 108 newly diagnosed BCR-ABL-negative MPN patients [including 55 patients with essential thrombocytopenia (ET) , 24 with polycythemia vera (PV) , and 29 with primary myelofibrosis (PMF) ] were identified using next-generation sequencing with 127-gene panel, and the relationship between gene mutations and clinical features were analyzed.Results:Total 211 mutations in 32 genes were detected in 100 MPN patients (92.59% ) , per capita carried (1.96±1.32) mutations. 85.19% (92/108) patients carried the driver gene (JAK2, CALR, MPL) mutations, 69.56% (64/92) of these patients carried at least 1 additional gene mutation. In descending order of mutation frequency, the highest frequency was for activation signaling pathway genes (42.2% , 89/211) , methylation genes (17.6% , 36/211) , and chromatin-modified genes (16.1% , 34/211) . There was a significant difference in the number of mutations in the activation signaling pathway genes, epigenetic regulatory genes, spliceosomes, and RNA metabolism genes among the three MPN subgroups. The average number of additional mutations in PMF patients was higher than that in ET and PV patients (1.69±1.39, 0.67±0.70, 0.87±1.22, χ2=13.445, P=0.001) . MPN-SAF-TSS (MPN 10 score) ( P=0.006) and myelofibrosis level ( P=0.015) in patients with ≥ 3 mutant genes were higher and the HGB level ( P=0.002) was lower than in those with<3 mutations. Twenty-six patients (24.1% ) carried high-risk mutation (HMR) , and patients with HMR had lower PLT ( P=0.017) , HGB levels ( P<0.001) , and higher myelofibrosis level ( P=0.010) and MPN10 score ( P<0.001) . The frequency of ASXL1 mutations was higher in PMF than in PV patients (34.5% vs. 4.2% , P=0.005) . PMF patients with ASXL1 had lower levels of PLT and HGB ( P=0.029 and 0.019) . Conclusion:69.56% of MPN patients carry at least one additional mutation, and 24.1% patients had HMR. Each subgroup had different mutation patterns. PMF patients had a higher average number of additional gene mutations, especially a higher frequency of ASXL1 mutation; PLT and HGB levels were lower in ASXL1 mutation PMF patients.

OBJECTIVE: To analyze the clinical features of chronic myeloid leukemia (CML) with T315 I mutation (CML-T315I) and compare the effectiveness of different treatments. METHODS: We retrospectively analyzed the clinical data and outcomes of 19 patients with CML-T315I receiving different treatments. The T315 I mutations in these patients were detected by examination of BCR-ABL kinase domain (KD) mutation by RTQ-PCR and Sanger sequencing. The relapse following the treatments, defined as hematological, cytogenetic and molecular biological recurrences, were analyzed in these patients. RESULTS: Of the 19 patients with CML-T315I, 14 (73.7%) were in CML-CP stage at the initial diagnosis, and 13 (81.2%) were high-risk patients based on the Sokal scores. All the 19 patients were treated with TKI after the initial diagnosis, and during the treatment, 15 (78.9%) patients were found to have additional chromosomal aberrations, and 10 (52.6%) had multiple mutations; 13 (68.4%) of the patients experienced disease progression (accelerated phase/blast crisis) before the detection of T315I mutation, with a median time of 40 months (5-120 months) from the initial diagnosis to the mutation detection. After detection of the mutation, 12 patients were treated with ponatinib and 7 were managed with the conventional chemotherapy regimen, and their overall survival rates at 3 years were 83.3% and 14.2%, respectively ( < 0.001). CONCLUSIONS CML patients resistant to TKI are more likely to have T315I mutations, whose detection rate is significantly higher in the progressive phase than in the chronic phase. These patients often have additional chromosomal aberrations and multiple gene mutations with poor prognoses and a high recurrence rate even after hematopoietic stem cell transplantation. Long-term maintenance therapy with ponatinib may improve the prognosis and prolong the survival time of the patients.
Drug Resistance, Neoplasm ; Fusion Proteins, bcr-abl ; Humans ; Imidazoles ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Mutation ; Pyridazines ; Retrospective Studies

Objective To evaluate the effect of duration of subcutaneous injection on the extent of bruising at injection sites among patients receiving low- molecular weight heparin. Methods Randomized clinical trials and quasi-experimental within-subject design that assessed the effect of subcutaneous duration on the bruising of injection sites were selected in Cochrane library, JBI evidence-based practice medical and nursing database, PubMed biomedical information retrieval platform, Medline general medical literature retrieval database. RevMan5.3 software was used to analyze the data after quality assessment, and data extraction were made for eligible trials. Results A total of 9 trials were included. The results of Meta-analysis supported the 30 s duration injection technique on reducing the rate of bruising of injection sites than 10 s duration injection technique (odds ratio was 0.34,95%confidence interval 0.25-0.47, P<0.01).While it was failed to support the effect on reducing the bruising area 48 and 72 hours after injection (P > 0.05). Conclusions Increasing the length of low-molecular weight heparin subcutaneous injection can reduce the rate of bruising. While it could not effectively reduce the area.

Objective: To analyze the association of cytogenetic abnormalities with the prognosis of chronic myeloid leukemia (CML) patients in tyrosine kinase inhibitors (TKI) era. Methods: Karyotype analysis of chromosome G-banding was carried out in 387 newly diagnosed CML patients by short-term culture of bone marrow cells. The correlation of cytogenetic abnormalities and CML progression was explored in combination with ABL tyrosine point mutations. Result: Of 387 patients with positive BCR-ABL fusion gene assayed by fluorescence in situ hybridization (FISH) technique, 94.1% (364/387) patients were Ph positive and 5.9% (23/387) Ph negative; 320 patients (87.9%) had a translocation t (9;22) (q34;q11) and 5 (1.4%) a variant translocation t (v;22) . Additional cytogenetic aberrations (ACA) at diagnosis were found in 10.7% (39/387) Ph⁺ patients, major route ACA in 22 (56.4%) cases and minor route ACA in 15 (38.5%) cases and 2 patients (5.1%) lacked the Y chromosome (−Y) ; 23.4% (71/303) patients occurred ACA during TKI treatment and the most frequent abnormalities were abnormal chromosome numbersd, which were likely associated with high proportion of disease progression (χ²=168.21, P<0.001) and ABL tyrosine point mutations (χ²=29.04, P<0.001) . Newly diagnosed CML-CP patients with t (9;22) (q34;q11) had a longer event-free survival (EFS) and disease-free survival (DFS) rates than that of patients with ACA (P=0.037; P=0.003) , while the overall survival (OS) had no significant differences (P=0.209) . As for CML-CP patients that occurred ACA during TKI therapy would have a marked low OS, EFS and DFS (all P<0.001) compared with no ACA occurred patients. Survival of advanced patients that occurred ACA were dramatically reduced. Conclusion ACA often emerged during the disease progress in CML patients, regular and timely detection of chromosomes karyotype and ABL tyrosine point mutations during TKI treatment was important for therapeutic evaluation, progress and prognosis of CML.

Objective: To investigate the clinical implications of p16 gene deletion in adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph⁺ ALL) . Methods: Retrospective analysis of clinical, immunophenotypic, cytogenetics, molecular characteristics and prognosis of 80 newly diagnosed Ph⁺ ALL patients with p16 deletion. Results: Of 80 adult Ph⁺ ALL, the prevalence of p16 gene deletion was 31.3%. p16 gene deletion carriers frequently accompanied with high WBC counts (WBC≥30×10⁹/L) and CD20 expression. The incidence of complex chromosome abnormality in p16 gene deletion group was higher than that in non-deletion group, with alternations in chromosome 7, 8, 19 and der (22) more frequently observed. There was no difference occurred between patients with or without p16 gene deletion in complete remission (CR) rate following induction chemotherapy combined with tyrosine kinase inhibitors (TKIs) . However, after three cycles of chemotherapy, the MMR and CMR rate in the p16 gene deletion group was lower than patients with wild-type p16 gene (P=0.034, P=0.036) . The p16 gene deletion patients showed no significant differences in MMR, CMR and relapse rate between Imatinib or Dasatinib plus chemotherapy (P>0.05) . Deletion of p16 gene was significantly associated with poor outcomes including worse overall survival (OS) (37.1% vs 54.1%, P=0.037) , lower disease free-survival (DFS) (12.4% vs 45.9%, P=0.026) , and increased cumulative incidence of relapse (P=0.033) . Among the 25 patients with p16 deletion, 14 underwent allo-HSCT and the median survival was 21 months, better than that of patients received chemotherapy alone (12 months) (P=0.030) . Conclusion This study indicated that deletion of p16 was associated with poor prognosis in adult Ph⁺ ALL, and the utility of second-generation TKI (Dasatinib) does not necessarily have an edge on efficacy over Imatinib, but allo-HSCT has the potential of elongating life expectancy. It is an important significance to define the status of p16 in Ph⁺ ALL for predicting prognosis and guiding therapy decision-making.

Objective To study the difference in clinical characteristics between respiratory syncytial virus(RSV) bronchiolitis and non-RSV bronchiolitis.Methods A retrospective review of the medical records of 541 children with bronchiolitis in Children's Hospital of Soochow University between January 2012 and December 2013 was conducted.The secretions of the lower respiratory tract were collected to detect RSV and other pathogens,the clinical characteristics between the 2 teams were analyzed by using PASW 21.0 software.Results (1)There were 194 patients(36％) hospitalized for bronchiolitis,who were assigned as RSV group,and 347 patients (64％) were assigned as non-RSV group.(2) Bronchiolitis due to RSV was more common from December to February,and bronchiolitis due to non-RSV was more common from May to October.(3) Compared with non-RSV group,RSV bronchiolitis started from a younger age(Z =5.62,P ＜0.001),pron to cyanosis(x2 =9.02,P =0.003),longer hospital stays,more expensive cost,more oxygen use,longer days of oxygen,ICU and mechanical ventilation,higher risk of ICU admission,higher the percentage of lymphocyte and platelet,the differences between 2 types were statistically significant(all P ＜ 0.05).White blood cell(WBC) count,neutrophils proportion and C-reactive protein(CRP) was higher in non-RSV than RSV bronchiolitis,the levels of lymphocyte,blood platelet and alanine aminotransferase (ALT) were higher in RSV than non-RSV bronchiolitis,the differences were statistically significant(all P ＜ 0.05).Conclusions Compared with non-RSV group,so RSV bronchiolitis is much more severe,and the patients need longer hospital stays and more expensive cost.Clinicians should pay close attention to RSV bronchiolitis.

To effectively screen treating pigmentation disorders drug, a new transgenic zebrafish drug screening model was constructed. Green fluorescent protein(GFP)were drived by tyrosinase-related protein 1a (tyrp1a)promoter specific expression in melanocyte. Effect of N-Phenylthiourea(PTU)and alpha-melanaocyte stimulating hormone(α-MSH)on the GFP expression and melanogenic of tyrp1a: eGFP zebrafish were photographed under the steromicroscope. Results showed that PTU could significantly inhibit the melanogenic and expression of GFP of zebrafish. As compared with control group, α-MSH treatment resulted in marked stimulation of body pigmentation and expression of GFP. In conclusion, a new transgenic zebrafish drug screening model was successfully established, which can be used for treating pigmentation disorders.

Objective To evaluate the value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for CT-positive mediastinal lymph nodes. Methods From September 2009 to December 2009, 28 patients with confirmed or suspected non-small-cell lung cancer with CT scan demonstrating enlarged ( ≥ 1 cm) mediastinal lymph nodes underwent EBUS-TBNA. The diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value were evaluated. Results 28 patients with 40 lymph nodes were studied. 27 patients had been performed successfully with enough specimens. No complications happened in the group. Mediastinal metastases were confirmed by EBUS-TBNA in 20 patients. 8 patients with benign mediastinal nodes as detected by EBUS-TBNA underwent surgery and mediastinal lymph node dissection, which confirmed N2 disease in 2 patients. Overall diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value of EBUS-TBNA in the detection of mediastinal metastasis were 92.9%, 90.9%,100%, 100%, 75% respectively. Conclusion EBUS-TBNA is a safe and effective technique for CT-positive mediastinal lymph nodes on CT scan.

Objective To investigate the expressions of cell phenotypes CD_8 and CD_(28) of peripheral blood lymphocytes in patients with colorectal cancer. Method CD_8 and CD_(28) of cell phenotypes were measured by flow cytometry in 50 patients with colorectal cancer (cancer group) and 30 nontumorous patients (control group). Results The expression of CD_8 in cancer group was significantly higher than that in control group [(32.24±8.38)% vs (22.18±7.55)%](P < 0.01). CD_(28) and CD_8~+/CD_(28)~+ were much lower than those in control group [(52.03±10.94)% vs (60.60±7.98)%,12.18±4.28 vs 16.38±4.94](P<0.01). CD_8~+/CD_(28)~+ in Dukes D stage patients were significantly lower than that in Dukes B stage patients (P<0.05). CD_(28) and CD_8~+/CD_(28)~+ in lymph node metastasis patients were much lower than those in lymph node negative patients (P < 0.01). CD_(28) and CD_8~+/CD_(28)~+ in serosa involved patients were lower than those in no serosa involved patients (P < 0.01). Conclusions The expressions of cell phenotypes CD_8 and CD_(28) of peripheral blood lymphocytes in patients with colorectal cancer are closely related to biological characteristics of the tumor. The assays of cell phenotypes CD_8 and CD_(28) might be useful for evaluating the immunal statement and prognosis of patients with colorectal cancer.