To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia / 中华血液学杂志

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

Research Progress of Comprehensive Utilization of Ziziphi Spinosae Semen and Its By-products / 中国实验方剂学杂志

As a traditional Chinese medicine， Ziziphi Spinosae Semen （ZSS） has the functions of tonifying liver， tranquilizing heart， astringent sweat and producing body fluid， which is used to treat neurasthenia， insomnia， dreaminess， debility， night sweat and so on. With the rapid and constant development of ZSS resource industry and its medicinal value， a large number of by-products and waste generated in the production and processing process， resulting in serious environmental problems. In general， the utilization rate of ZSS resources was still not high. Based on this， the chemical components and potential resources of ZSS were systematically combed from the perspective of the medicinal parts and bioactive components in this paper， and the authors had summarized that the widely application of ZSS and its by-products （fruit， leaf， root， etc.） in the fields of food， medicine， functional food and other areas was discovered and summarized as feed， feed additives， activated carbon， organic fertilizer， etc. In addition， this paper systematically summarized the current environmental protection problems of the industry， and put forward suggestions for improvement， aiming at reducing environmental pollution and improving the utilization efficiency of resources， so as to provide reference and basis for the comprehensive utilization of ZSS and its by-products， and promote the green， economical and double-effect development of the industry.

Sevoflurane preconditioning protects myocardial ischemia/reperfusion injury by increasing plasma adiponectin levels / 中国药理学通报

Aim To investigate whether adiponectin is involved in the protective effect of sevoflurane preconditioning on myocardial ischemia/reperfusion (MI/R) injury. Methods C57 mice were randomly divided into four groups; the Sham Control (sham group), the MI/R-Control (model group), the MI/R-Sevopre (pretreatment group) and the APN-KO-MI/R-Sevopre (knockout pretreatment group). The plasma adiponectin level was detected 24 h after MI/R modeling. Meanwhile, the left ventricular end-systolic diameter, end-diastolic diameter and ejection fraction were measured at 24 h. In addition, TUNEL staining was used to detect the left ventricular end-systolic diameter, end-diastolic diameter and ejection fraction and the morphology and apoptosis of myocardial cells in each group were observed. What' s more, the infarct area was observed by Evans blue TTC staining. Results Compared with sham group, model group had impaired heart function, decreased ejection fraction and increased end-diastolic and end-systolic diameters. Meanwhile, the myocardial infarction area and apoptotic cells significantly increased in model group, and the plasma adiponectin level decreased. However, compared with model group, mice in sevoflurane pretreatment group had improved heart function, decreased myocardial infarction area, decreased apoptotic cells and increased plasma adiponectin levels. And then, compared with pretreatment group, sevoflurane pretreatment in knockout pretreatment group reduced Ml/R injury. Conclusion The sevoflurane pretreatment protects MI/R injury by increasing plasma adiponectin levels.

Analysis on the trend of overweight and obesity of children and adolescents in 9 provinces of China from 1991 to 2015 / 中华预防医学杂志

To analyze the trends of overweight and obesity of children and adolescents in 9 provinces of China from 1991 to 2015. A total of 14 888 children and adolescents aged 6-17 years with complete data were selected from the China Health and Nutrition Survey from 1991 to 2015. The definitions of overweight and obesity were defined using the international body mass index (BMI) cut-offs for child overweight and obesity established by the International Obesity Task Force in 2000 (hereinafter referred to as 'IOTF Standard'), the growth reference for school-aged children and adolescents established by the World Health Organization in 2007 (hereinafter referred to as 'WHO Standard'), the BMI cut-offs for screening overweight and obesity in Chinese children established by Li Hui et al. in 2009 (hereinafter referred to as 'Expert Standard'), and the screening thresholds for overweight and obesity in Chinese school-age children and adolescents released by the National Health and Family Planning Commission in 2018 (hereinafter referred to as 'Industry Standard'). Multivariable linear regression model was used to examine the trends in BMI values from 1991 to 2015, and multivariable logistic regression model was used to examine the trends in the prevalence of overweight and obesity from 1991 to 2015. After adjusting for the age, sex and region, BMI values increased from 17.26 kg/m(2) in 1991 to 18.72 kg/m(2) in 2015 ( value for trend <0.001). The prevalence of overweight defined by the IOTF Standard, WHO Standard, Expert Standard, and Industry Standard increased from 4.06%, 5.37%, 5.16%, and 4.27% in 1991 to 13.58%, 16.23%, 13.30%, and 11.70% in 2015, respectively (all values for trend <0.001), and the prevalence of obesity increased from 1.02%, 1.86%, 2.24%, and 2.41% in 1991 to 7.45%, 10.75%, 12.08%, and 12.74% in 2015, respectively (all values for trend <0.001). The BMI values and prevalence of overweight and obesity increased significantly in Chinese children and adolescents from nine provinces from1991 to 2015.

Correlation between Histone Deacetylase 9 and Regulatory T Cell in Patients with Chronic Heart Failure / 华中科技大学学报（医学）（英德文版）

Heart failure (HF) is the end stage of various kinds of cardiovascular diseases and leads to a high mortality worldwide.Numerous studies have demonstrated that frequencies of CD4+CD25+Foxp3+ regulatory T cells (Tregs) are reduced in HF patients and properly expanding Tregs attenuates HF progression.Histone deacetylase (HDAC) 9 has been revealed to contribute to several cardiovascular and cerebrovascular diseases.Plenty of studies showed that HDAC9 negatively regulated the number and function of Tregs.Thus,we aim to investigate the expression of HDAC 9 in patients with chronic heart failure (CHF) and the relationship among HDAC9,Tregs and CHF.Our research showed a reduced number of Tregs and an increased expression of HDAC9 mRNA in CHF patients.Patients with CHF were divided into two groups by heart function grade of New York Heart Association (NYHA),we found that the HDAC9 mRNA expression level in NYHA grade Ⅱ-Ⅲ group were lower than that in NYHA grade Ⅳ group.More importantly,the correlation study suggested that the expression of HDAC9 mRNA was negatively correlated to Tregs frequency and left ventricular ejection fraction (LVEF),whereas positively correlated to larger left ventricular end-diastolic dimension (LVEDD) and B-type natriuretic peptide (BNP) in patients with CHF.The correlation studies also showed a positive correlation between HDAC9 and the severity of CHF.Our research suggests that HDAC9 may be a new indicator for assessing CHF and it may offer a new direction for research of CHF.

Correlation between Histone Deacetylase 9 and Regulatory T Cell in Patients with Chronic Heart Failure / 华中科技大学学报（医学）（英德文版）

Heart failure (HF) is the end stage of various kinds of cardiovascular diseases and leads to a high mortality worldwide.Numerous studies have demonstrated that frequencies of CD4+CD25+Foxp3+ regulatory T cells (Tregs) are reduced in HF patients and properly expanding Tregs attenuates HF progression.Histone deacetylase (HDAC) 9 has been revealed to contribute to several cardiovascular and cerebrovascular diseases.Plenty of studies showed that HDAC9 negatively regulated the number and function of Tregs.Thus,we aim to investigate the expression of HDAC 9 in patients with chronic heart failure (CHF) and the relationship among HDAC9,Tregs and CHF.Our research showed a reduced number of Tregs and an increased expression of HDAC9 mRNA in CHF patients.Patients with CHF were divided into two groups by heart function grade of New York Heart Association (NYHA),we found that the HDAC9 mRNA expression level in NYHA grade Ⅱ-Ⅲ group were lower than that in NYHA grade Ⅳ group.More importantly,the correlation study suggested that the expression of HDAC9 mRNA was negatively correlated to Tregs frequency and left ventricular ejection fraction (LVEF),whereas positively correlated to larger left ventricular end-diastolic dimension (LVEDD) and B-type natriuretic peptide (BNP) in patients with CHF.The correlation studies also showed a positive correlation between HDAC9 and the severity of CHF.Our research suggests that HDAC9 may be a new indicator for assessing CHF and it may offer a new direction for research of CHF.

Expression and Clinical Significance of Leukemia Stem Cell Antigen in Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the expression characteristics of leukemia stem cell (LSC) antigen in acute myeloid leukemia (AML) and to explore the correation of LSC-specific antigens with the subtypes, cytogenetics and clinical efficacy of AML.@*METHODS@#A total of 61 newly diagnosed patients with AML (except M3) hospltalized in Department of Hematology of our hopital were selected from January 2013 to March 2016. The immun phenotypes and expression of Tim-3, CD96 and CD123 on leucamia cells were detected by direct immunofluorescenct flow cytometry. 61 patients were divided into positive expression and megative expression groups according to expression of Tim-3, CD96 and CD123; the correlation of LSC antigen expression level with high WBC count, chromosome and therapeutic efficacy was analyzed.@*RESULTS@#Among 61 newly diagnosed patients with AML (except M3), the expression rate of Tim-3, CD96 and CD123 was 52.45%, 44.26% and 55.73% respectively. The expression rates of Tim-3, CD96 and CD123 between the AML subtypes and total patients was not stetistically different (P>0.05). The high WBC count occurred more easily in AML (except MS) patients with positive expression of Tim-3, CD96 and CD123, but compared with AML patients with negative espression, the difference was not statstically significant (P>0.05). The proportion of chromosone karyotype with poor prognosis detected in patients with positive expression of Tim-3 and CD96 was higher than that in patients with negative expreesion (P0.05). After 2 courses of chemotherapy, the complete remission (CR) rate in patients with positive expression of Tim-3, CD96 and CD123 was significantly lower than that in patients with negative expression of Tim-3, CD96 and CD123 (P0.05), while the difference of OS time in patients with positive and negative expression of CD123 was not significant (P>0.05).@*CONCLUSION@#The expression levels of Tim-3, CD96 and CD123 in newly diagnosed AML (except M3) sybtype patients are not significantly different form those in total patients. The high WBC count ocours more easily in patients with positive expression of Tim-3, CD96 and CD123. After 2 course of chemotherapy, the CR rate in patients with positive expression of Tim-3, CD96 and CD123 was significantly lower than that in patients with negative expression. The proportion of chromsome karyotype with poor prognosis detected in patients with positive expression of Tim-3 and CD96 is high, moreover, OS time in patients with positive expression of Tim-3 and CD96 is shorter than that in patients with negative expression.

Transcription Factor Pax5 Promotes B-lymphomagenesis in a Promoter-Independent Manner / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To determine whether B lymphocyte-specific transcription factor Pax5 regulates B-lympho-magenesis without direct binding to promoter.</p><p><b>METHODS</b>Mouse B-lymphoma cell line myc3 and 38B9 were infected with GFPtagged retrovirus that encodes wide type or various mutant pax5 genes. After viral infection for 48 hours, the percentage of GFP positive lymphoma cells was determined by flow cytomety. The percentage of GFP positive tumor cells was further monitored every 3 days in vitro or once the tumor was formed in vivo. Both cell cycle and apoptic cell number of GFP positive lymphoma cells were analyzed using flow cytometry.</p><p><b>RESULTS</b>Similar to the infection with wild type Pax5 retrovirus, infection with Pax5 mt 1-357 and Pax5 mt 304-358 that lacks of DNA binding motif can strongly increase the percentage of GFPB-lymphoma cells both in vitro and in vivo (P<0.01), while infection with empty viral vector migR-GFP and Pax5 mt 1-143 containing only DNA binding motif failed to increase the percentage of GFP positive tumor cells (P>0.05). Moreover, the analysis of flow cytometry demonstrated that more B-lymphoma cells infected with wild type Pax5, Pax5 mt 1-357 and Pax5 mt 304-358 retroviruses entered S and G/M phases in comparison with those infected with empty viral vector migR-GFP and Pax5 mt 1-143. Apoptotic rates among different groups were not significantly changed.</p><p><b>CONCLUSION</b>Pax5 can promote B-lymphoma cell growth both in vitro and in vivo in a promoter-independent manner. This is mainly due to the accelerating of cell cycle rather than decreasing apoptosis. Our studies provide potential theory for restraing B-lymphomagenesis by targeting the specific Pax5 domains.</p>

Quantitative determination of rivastigmine in rat plasma and tissues by HPLC-MS/MS method / 中国药学杂志

OBJECTIVE: To establish a highly accurate, sensitive and credible high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the determination of rivastigmine in rat plasma and tissues. METHODS: All biological samples were extracted with ethyl acetate. Chromatographic separation was performed on an Agilent C18 column (4.6 mm × 100 mm, 3.5 μm) using water-methanol (20:80) as mobile phase at a flow rate of 0.3 mL · min-1. The MS analysis was performed by multiple reaction monitoring (MRM) with electronic spray ionization source (ESI+) for quantitative response of rivastigmine (251.3 → 206) and the internal standard, antipyrine (189.1 → 106.1) respectively. RESULTS: The calibration curves of rivastigmine in plasma and tissues showed satisfactory linearity, and the relative extraction recovery of three concentrations in plasma and all tissues were over 60% except some individuals and all RSDs met the requirements. The limit of quantification of rivastigmine in plasma and tissues were 0.1 and 0.2 ng · mL-1 respectively. CONCLUSION: The method is rapid, accurate, highly selective and sensitive, and is suitable for the quantitative analysis of rivastigmine in biological sample of rats. Copyright 2012 by the Chinese Pharmaceutical Association.

Prognostic significance of serial determinations of lactate dehydrogenase in follow-up for patients with myelodysplastic syndrome / 中国实验血液学杂志

This study was aimed to dynamically observe the expression level of lactate dehydrogenase (LDH) in MDS patients and to explore the significance of LDH level for prognostic judgement of MDS patients. The expression level of LDH in 163 confirmedly diagnosed patients from 2001 to 2009 years in our hospital, the changes of LDH level in follow-up patients and relation of the LDH changes to prognosis, survival time and MDS progression, as well as the relation of LDH level to blood cell count, ratio and karyotype of blast cells in bone marrow were analyzed retrospectively. The results showed that the median LDH level in 163 MDS patients at diagnosis was 214 U/L (range 102 - 865 U/L), the median survival time of patients with increased LDH (> 240 U/L) was 25.6 months which was significantly shorter than that of patients with normal LDH level (56.8 months)(p < 0.05). When MDS patients were classified according to IPSS, the increased LDH level in MDS patients was observed in high risk and intermediate II groups (337.20 ± 298.00 U/L and 234.07 ± 216.00 U/L, respectively) which was significantly higher than that in low risk group (154.94 ± 46.08 U/L) (p < 0.05). The LDH level in patients with MDS progression was obviously enhanced while LDH level in patients without progression was not enhanced, mainly maintained in stable level as compared with LDH level at diagnosis and before progression (p < 0.005). By multivariate analysis, the increase of LDH level was found to be an independent prognostic factor. It is concluded that the LDH level may be used as indicator for judging prognosis of MDS patients, which is helpful to early recognition of MDS progression and risk stratification of disease, as well as selection of rational therapy.

Inducible nitric oxide synthase and Fas/FasL with C3 expression of mouse retinal pigment epithelial cells in response to stimulation by peroxynitrite and antagonism of puerarin / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Retinal pigment epithelial (RPE) cell is a monolayer of multifunctional cells between the retina and the choroid. Peroxynitrite (ONOO(-)) is known to induce toxicity on RPE cells. This study aimed to evaluate ONOO(-) induced expression of inducible nitric oxide synthase (iNOS) and complement 3 (C3) via Fas/FasL pathway in RPE cells and the values of puerarin as a therapeutic target for inhibiting the apoptosis of RPE cells.</p><p><b>METHODS</b>RPE cells were obtained from eyes of C57BL/6 mice. RPE cells were divided into control, ONOO(-) and puerarin groups. Control group was treated with saline, ONOO(-) group was treated with ONOO(-), and puerarin group was treated with puerarin after added with ONOO(-). All changes were observered at 6, 12 and 24 hours after treatment. Western blotting analysis was used to determine the expression of nitrotyrosine (NT, the foot print of ONOO(-)) and C3; flow cytometry was used to determine the apoptosis of RPE cells. Immunohistochemistry and Western blotting were used to determine Fas/FasL signal transduction. Gene array analysis, reverse transcription polymerase chain reaction (RT-PCR) and Western blotting were used to determine the expression of iNOS mRNA and iNOS protein in RPE cells.</p><p><b>RESULTS</b>There were minor expression of NT, C3, Fas/FasL and iNOS mRNA in control group, and strong expression of NT and C3 in ONOO(-) group, while in puerarin group weak expressions of NT and C3 were detected as time passed by (P < 0.001). Apoptosis of RPE cells occured and reached a higher level at 6 and 24 hours after addition of ONOO(-) respectively in ONOO(-) group, but delayed apoptosis in puerarin group (P < 0.05). Compared to control group, the expression of Fas/FasL was up-regulated in ONOO(-) group, but was down-regulated in puerarin group (P < 0.001). Similarly, the expressions of iNOS mRNA and iNOS protein in ONOO(-)group were up-regulated in ONOO(-) group, but down-regulated in puerarin group (P < 0.001).</p><p><b>CONCLUSIONS</b>ONOO(-) expresseion in RPE cells may constitute the new way of oxidant stress. Fas/FasL signal transduction pathway and C3 may affect and reinforce apoptosis mediated by ONOO(-). Puerarin could reverse ONOO(-) damage on RPE cells. The antagonizing mechanism of puerarin may be related to its inhibitory to the expression of iNOS mRNA, and therefore decrease ONOO(-) formation as well as directly antagonize the effect of ONOO(-). Furthermore, puerarin may be an useful therapeutic agent against apoptosis of RPE cells.</p>

Construction of tissue engineered porcine corneal stroma with skin fibroblasts / 上海第二医科大学学报

Objective To explore the feasibility of constructing tissue engineered porcine corneal stroma with skin fibroblasts in vivo.Methods Skin fibroblasts were isolated from embryonic porcine,cultured and expanded in vitro.Cells were labeled with green fluorescence protein(GFP) gene by retro-viral infection.Cells at passage 3 were seeded on polyglycolic acid(PGA) non-woven fibers to form a cell-scaffold complex.The complexes were then implanted into porcines' corneal stroma after culturing in vitro for 1 week.Engineered stroma was observed continuously and harvested after 8 weeks for gross and histological evaluation.PGA with corneal stromal cells was served as control. Results The engineered tissue in the stroma gradually became transparent over a period of 8 weeks,showing no difference with the control group.Histologically,the engineered stromal lamellar was relatively regular and similar to the control.The implanted cells were confirmed by GFP expression under fluorescent microscope.By transmission electron microscopy examination, no significant difference in the diameter of collagen fiber was observed between the engineered stroma and normal stroma. Conclusion Tissue engineered corneal stroma may be formed with skin fibroblasts in porcine corneal microenvironment.

On The Functions of History of Science Educating People / 中华医学教育探索杂志

Education of history of science may not only cultivate spirit of science,critical spirit,methods of thought,innovative spirit and sense of responsibility,compassion and enterprise,but also provide cognition on illogical methods of thought and taste of aesthetic philosophy.Education of history of science in Medical academy is an important channel to advance medicos' comprehen- sive quality.Enhancing cognition and developing multifarious educating activities of history of science is an important tendency in reformation of medical education.