Factors influencing severe cytopenia in chronic phase chronic myeloid leukemia patients receiving initial second generation tyrosine kinase inhibitors and its impact on treatment responses and outcomes / 中华血液学杂志

Objective: To explore the influencing covariates of severe neutrophils and/or thrombocytopenia and their effect on treatment response and outcome in patients with chronic-phase chronic myeloid leukemia (CP-CML) receiving initial second-generation tyrosine kinase inhibitors (2G-TKI) . Methods: Data from consecutive patients aged ≥18 years with newly diagnosed CP-CML who received initial 2G-TKI at Peking University People's Hospital from September 2008 to November 2021 were interrogated. Binary logistic regression models and Fine-Gray and Cox regression models were applied. Results: Data from 267 patients who received initial 2G-TKI, including nilotinib (n=239, 89.5% ) and dasatinib (n=28, 10.5% ) , were interrogated. The median age was 36 (range, 18-73) years, and 156 (58.4% ) patients were male. At a median treatment period of 1.0 (0.1-3.0) month, 43 (16.1% ) patients developed grade ≥3 neutrophils and/or thrombocytopenia and recovered within 1.0 (0.1-24.6) month. Male (OR=2.9, 95% CI 1.2-6.8; P=0.018) , age of ≥36 years (OR=3.2, 95% CI 1.4-7.2, P=0.005) , a spleen below a costal margin of ≥7 cm (OR=2.8, 95% CI 1.2-6.6, P=0.020) , and a hemoglobin (HGB) level of <100 g/L (OR=2.9, 95% CI 1.3-6.8, P=0.012) at diagnosis were significantly associated with grade ≥ 3 neutrophils and/or thrombocytopenia. Based on their regression coefficients, male, age of ≥36 years, a spleen below a costal margin of ≥7 cm, and an HGB level of <100 g/L were given 1 point to form a predictive system. All patients were divided into three risk subgroups, and the incidence of severe cytopenia significantly differed among the three groups (P < 0.001) . Grade ≥3 neutrophils and/or thrombocytopenia for >2 weeks was significantly associated with lower cumulative incidences of complete cytogenetic response (CCyR, HR=0.5, 95% CI 0.3-0.7, P<0.001) and major molecular response (MMR, HR=0.4, 95% CI 0.3-0.8, P=0.004) and was not significantly associated with failure, progression, and survival. Conclusion: Male, advanced age, a large spleen, and a low HGB level were significantly associated with severe cytopenia. The four covariates were used to establish a prediction model, in which the incidence of severe cytopenia among different risk groups was significantly different. Severe cytopenia for >2 weeks was a negative factor for responses but not for outcomes.

Combination of socio-demographic and clinical co-variates for predicting treatment responses and outcomes in patients with chronic myeloid leukemia in the chronic phase / 中华血液学杂志

Objective: To explore the impacts of socio-demographic and clinical co-variates on treatment responses and outcomes in patients with chronic myeloid leukemia in the chronic phase (CML-CP) receiving tyrosine kinase inhibitor (TKI) and identified the predictive models for them. Methods: Data of newly diagnosed adult patients with CML-CP receiving first-line TKI and having complete socio-demographic data and clinical information were reviewed. Cox model was used to identify the independent variables associated with complete cytogenetic response (CCyR) , major molecular response (MMR) , molecular response 4 (MR(4)) and molecular response 4.5 (MR(4.5)) , as well as failure-free survival (FFS) , progression-free survival (PFS) , overall survival (OS) and CML-related OS. Results: A total of 1414 CML-CP patients treated with first-line imatinib (n=1176) , nilotinib (n=170) or dasatinib (n=68) were reviewed. Median age was 40 (18-83) years and 873 patients (61.7% ) were males. Result of the multivariate analysis showed that lower educational level (P<0.001-0.070) and EUTOS long-term survival intermediate or high-risk (P<0.001-0.009) were significantly associated with lower cumulative incidences of CCyR, MMR, MR(4) and MR(4.5), as well as the inferior FFS, PFS, OS and CML-related OS. In addition, those who were males, from rural households, had white blood cells (WBC) ≥120×10(9)/L, hemoglobin (HGB) <115 g/L and treated with first-line imatinib had significantly lower cumulative incidences of cytogenetic and/or molecular responses. Being single, divorced or widowed, having, rural household registration, WBC≥120×10(9)/L, HGB<15 g/L, and comorbidity (ies) was significantly associated with inferior FFS, PFS, OS, and/or CML-related OS. Thereafter, the patients were classified into several subgroups using the socio-demographic characteristics and clinical variables by cytogenetic and molecular responses, treatment failure and disease progression, as well as overall survival and CML-related OS, respectively. There were significant differences in treatment responses and outcomes among the subgroups (P<0.001) . Conclusion: Except for clinical co-variates, socio-demographic co-variates significantly correlated with TKI treatment responses and outcomes in CML-CP patients. Models established by the combination of independent socio-demographic and clinical co-variates could effectively predict the responses and outcome.

Roles of c-Fos, EGR-1, PKA, and PKC in cognitive dysfunction in rats after propofol anesthesia

Abstract This study aimed to investigate possible changes in the spatial memory of rats and the expression or activity of EGR-1, c-Fos, PKA, and PKC after propofol anesthesia. Thirty-six Sprague-Dawley rats aged 20 months and 36 Sprague-Dawley rats aged three months were each randomly divided into three groups: the control group, the Morris Water Maze (MWM) group, and the propofol group. In the propofol groups of both young and aged rats, the rats were anesthetized by propofol for two or four hours and then performed the MWM test two days or two weeks after anesthesia to assess cognitive function. EGR-1, c-Fos, PKA, and PKC expressions in the rat hippocampus were determined via immunohistochemistry. For the older rats, the escape latency in the P4h/2d group was significantly prolonged (P < 0.05), and the learning curve was right-shifted in the P4h/2w group (P < 0.05). The expression levels of EGR-1, c-Fos, PKA, and PKC in the MWM groups were significantly higher than those in the control groups (P < 0.05). In the P4h/2d group of aged rats, the expression levels of both PKA and PKC were decreased compared with those of the MWM groups. The decreased expression of both protein kinases may be responsible for the observed impairment after propofol anesthesia

Heparin-binding hemagglutinin as a composition antigen of tuberculosis vaccine exerts protective immune effects by inducing IL-17 / 中华预防医学杂志

To explore the protective immune effect induced by mucosal delivery heparin-binding hemagglutinin (HBHA)-a candidate vaccine antigen of Mycobacterium tuberculosis. Female C57BL/6 mice were between 6 and 8 weeks of age before experimental use. Thirty mice received different immunization strategies and were randomly divided into the control group, the early secreting antigen target-6 (ESAT-6) intranasal immunization group, the HBHA intranasal immunization group, the BCG priming PBS control group, or BCG priming HBHA boost group, 6 mice in each group. In order to analyzed the immune effect, the concentrations of plasma Interleukin-17A (IL-17A) and other cytokines were measured by ELISA. Quantitative real-time PCR analyses were performed to detect the relative quantity (RQ) mRNA of IL-17A in the lung. The lung tissue sections were stained to detect the formation of the tertiary lymphoid structures. The chemokines contributed to formation of the tertiary lymphoid structures were also measured. Flow cytometry was used to detect the frequency of Th1 and Th17 cells in the system. Sixty mice in the BCG priming PBS control group and the BCG priming HBHA boost group were sacrificed at different time points after infection to count the lung bacterial burden. The concentrations of plasma IL-17A and relative quantity of lung IL-17A mRNA were highest in the BCG priming HBHA boost group [(14.76±4.73) pg/mL,RQ (12.27±6.71)], which was significantly higher than the control group [(5.57±2.95) pg/mL,RQ (1.30±0.97)] (t=4.213, P<0.001; t=5.984, P<0.001), and also significantly higher than the BCG priming PBS control group [(6.81±2.18) pg/mL,RQ (1.44±1.16)] (t=3.646 P=0.001; t=6.185 P<0.001). Compared with the BCG priming PBS control group (0.38±0.38)% the frequency of spleen Th17 cells were also significantly increased (t=-0.280 , P=0.048) in the BCG-primary HBHA boost group (1.02±0.34)%. In addition, HBHA boosting could promote better formation of the tertiary lymphoid structures in the lung, and decrease the bacterial load on the early stage after BCG challenge. Collectively, mucosal delivery of HBHA can effectively enhance the protective effect after BCG vaccination, and it is a potential candidate vaccine component.

Implications, spiritual characteristics and practical significance of Chinese schistosomiasis control culture / 中国血吸虫病防治杂志

The culture of schistosomiasis control is specific in the history of Chinese culture. Broadly speaking, the culture of schistosomiasis control is a summary of specific social mood, social consciousness and material culture created by Chinese populations during the progress of schistosomiasis control since the founding of the People’s Republic of China. Narrowly speaking, the culture of schistosomiasis control is the spiritual culture that is jointly created and nurtured by schistosomiasis control workers since the founding of the People’s Republic of China. The spiritual features of Chinese schistosomiasis control culture are characterized by the patriotism and care about the people, the matter-to-fact attitude, the pioneering and enterprising spirit, and the spirit of sacrifice and dedication. The ultimate goal of the research on the culture of schistosomiasis control is to facilitate the achievement of the strategic goal of Healthy China 2030 as scheduled, accelerate the progress towards elimination of schistosomiasis, and to promote the sustainable development of schistosomiasis control in China.

Dissection of seed development of Gastrodia elata at different temperatures / 中国中药杂志

The study is aimed to create seed materials and dissect the molecular mechanism of sexual propagation of Gastrodia elata. In this research, thirteen characteristics of flowers, flower stem, fruits, seeds and embryo of G.elata f. glauca and G.elata f. elata after bolting at room temperature(RT) and constant temperature(CT, 22 ℃) were determined. It was found that the constant temperature condition could prolong the bolting duration of G.elata and increased the number of flowers, while the variety of G.elata only affected the bolting duration, but had no effect on the number of flowers, and the G.elata f. elata was more likely to bolting than the G.elata f. glauca. The variety of G.elata was the main factor affecting the time of dehiscent fruit of G.elata, the temperature was the main factor affecting the fruits number and fruits diameter, and the constant temperature was more conducive to the fruits shape of G.elata than the room temperature. There was no significant difference in seed phenotype of G.elata varieties, but the seed embryo of G.elata seeds cultivated at constant temperature was fuller than that of G.elata cultivated at room temperature, and temperature had less influence on the seed phenotype of G.elata. But it was interesting to find that temperature and varieties had greater influence on the seed embryo of G.elata, constant temperature cultivation was more conducive to the formation of seed embryo of G.elata, and more the seed embryo of G.elata f. elata was easier to form than the seed embryo of G.elata f. glauca. However, the development of seeds and embryos of G.elata was significantly affected, and the development of seeds and embryos of G.elata f. glauca was more sensitive to temperature than G.elata f. elata. The research suggested that it is advisable for G.elata to produce seed materials by bolting at constant temperature(22 ℃).

Analysis of the efficacy and influencing factors of nilotinib or dasatinib as second- or third-line treatment in patients with chronic myeloid leukemia in the chronic phase and accelerated phase / 中华血液学杂志

Objective: To explore the efficacy and prognosis of nilotinib or dasatinib as second- or third-line treatment in patients with chronic myeloid leukemia (CML) in the chronic phase (CP) and accelerated phase (AP) . Methods: From January 2008 to November 2018, the data of CML patients who failed first- or second-line tyrosine kinase inhibitor (TKI) -therapy received nilotinib or dasatinib as second-line and third-line therapy were retrospectively reviewed. Results: A total of 226 patients receiving nilotinib or dastinib as second-line (n=183) and third-line (n=43) therapy were included in this study. With a median follow-up of 21 (range, 1-135) months, the cumulative rates of complete hematological response (CHR) , complete cytogenetic response (CCyR) and major molecular response (MMR) were 80.4%, 56.3%and 38.3%, respectively in those receiving TKI as second-line TKI therapy. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 78.7%and 93.1%, respectively. Multivariate analyses showed that Sokal high risk, female gender, the best response achieved <CHR on the first-line TKI-therapy, the interval from diagnosis to switching to second-line TKI ≥18 months, AP or hematologic failure, or non-specific mutation of BCR-ABL kinase domain before second-line TKI therapy, developing severe hematologic toxicity during the second-line TKI therapy were variables associated with poor responses or outcomes on second-line TKI therapy. With a median follow-up of 6 (range, 3-129) months, the cumulative CHR, CCyR and MMR were 95.7%, 29.3%, and 18.6%, respectively in those receiving the third-line TKI therapy. The 2-year PFS and OS rates were 66.8% and 93.8%, respectively. The patients with an interval from diagnosis to starting TKI ≥6 months, achieving no cytogenetic response on the second-line TKI, the interval from diagnosis to starting second-line TKI ≥60 months, and progression to AP before the third-line TKI therapy had lower probabilities of responses and unfavorable outcomes. Conclusions: The efficacy of dasatinib and nilotinib as second- or third-line TKI-therapy were active in the CML patients with TKI-resistance. The best response achieved on previous TKI-therapy, the disease phase before switching TKI, and the severe hematologic toxicity developing on the current TKI-therapy were associated with the responses and outcomes.

Fingerprint of Epimedium wushanense Based on Principal Component，Factor and Cluster Analysis / 中国实验方剂学杂志

Objective: To establish the fingerprint of Epimedium wushanense by HPLC,and study the comprehensive quality of E. wushanense by combining principal components,factors and cluster analysis,so as to provide theoretical basis for its quality evaluation. Method: The chromatographic column was Agilent infinitylab poroshell 120 SB-C18 (3.0 mm×100 mm,2.7 μm),the flow phase was acetonitrile (A)-water (B) with a gradient of 0-5 min,25%-26%A;5-6 min,26%-34%A;6-11 min,34%-38.5%A;11-17 min,38.5%-100%A;17-20 min,100%A,the flow rate was 0.8 mL·min- 1,the detection wavelength was 270 nm,and the column temperature was 30℃. Result: The cluster analysis better classified E. wushanense from different producing areas. E. wushanense from Guizhou province and E. wushanense from Chongqing were classified as class Ⅱ. E. wushanense from Guizhou province and Chongqing were far apart, indicating that the quality of E. wushanense varies from place to place affected by environment and climate. The results of principal component analysis showed that the quality of E. wushanense produced in Chongqing was better than that of E. wushanense produced in Guizhou. Among them,CQWS-02 (Yaque village,Guanyang town,Wushan county,Chongqing) and CQWS-10 (Hewan, Guanyang town,Wushan county,Chongqing) can be considered in the selection of high-quality varieties. In addition,No.1 common peak (epimedin A),No.2 common peak (epimedin B),No.4 common peak (icariin) and No.5 common peak (unknown component) in the fingerprint of the test samples could be used as the evaluation index components of E. wushanense quality. Conclusion: Principal components,factors and cluster analysis are used to achieve the rapid analysis, and their respective advantages are brought into full play for mutual verification and supplement. And the quality of E. wushanense in different origins can be comprehensively evaluated in all-round ways.

Application of Two-parameter Scoring System Based on CD105 and CD117 in MDS Diagnosis / 中国实验血液学杂志

OBJECTIVE@#To study the value of flow cytometric scoring system in the diagnosis of myelodysplastic syndromes (MDS).@*METHODS@#The phenotypes of erythroid and immature cells were analyzed retrospectively in 130 MDS patients, 19 healthy controls and 89 pathological controls, all of them were well clinically immunophenotyped. The 4-parameter scoring system reported in the literature was studied, including myeloblast-related cluster size, B-progenitor-related cluster size, lymphocyte to myeloblast CD45 ratio, and granulocyte to lymphocyte side scatter ratio. The two flow cytomatric parameters of the erythroid scoring system were analyzed, including CD36 coefficient of variation (CV) and CD71CV. According to our previous study, the percentage of CD117CD105 myeloid progenitor cells and the proportion of CD105 cells in CD117 cells were selected to establish a two-parameter scoring system, and compared with the four-parameter scoring system and the erythroid scoring system.@*RESULTS@#The sensitivity of the four-parameter scoring system and the erythroid scoring system for the diagnosis of low-risk MDS was 43.5% and 63.0%, and the specificity was 87.0% and 63.9%, respectively. After combining the two scoring systems, the sensitivity to diagnose low-risk MDS was 73.9% and the specificity was 62.0%. The sensitivity of the two-parameter scoring system for the diagnosis of low-risk MDS was 76.1% with a specificity of 81.5%. Combined with the four-parameter scoring system, the sensitivity was increased to 78.3%, but the specificity was reduced to 71.3%. After combining with the erythroid scoring system, the sensitivity reached 87.0%, but the specificity was reduced to 54.6%.@*CONCLUSION@#Using the two-parameter scoring system alone can achieve great sensitivity and specificity in the diagnosis of low risk MDS.

Changes of serum galectin-3 and pentraxin-3 levels in CHF patients and their correlation with progno-sis / 心血管康复医学杂志

Objective :To explore changes of serum levels of galectin-3 and pentraxin-3 (PTX-3) in patients with chro-nic heart failure (CHF) and their correlation with prognosis .Methods : A total of 150 CHF patients (CHF group) treated in our hospital and 150 healthy volunteers undergoing physical examination simultaneously (healthy group ) from Jan 2015 to Dec 2015 were enrolled .Serum levels of galectin-3 ,PTX-3 and N-terminal pro brain natriuretic peptide (NT-proBNP) ,left atrial diameter (LAD) ,left ventricular end-diastolic dimension (LVEDd) and left ven-tricular mass index (LVMI) were compared between two groups at enrollment .According to one-year follow-up out-come ,CHF group (12 cases lost ,another 138 cases) was divided into poor prognosis group (n＝36) and good prog-nosis group (n＝102).Spearman linear correlation analysis was used to analyze correlation among serum galectin-3 , PTX-3 levels and poor prognosis of CHF patients .Results :Compared with healthy group ,there were significant rise in serum levels of galectin-3 [ (2-23 ± 0-25) ng／ml vs .(16-61 ± 1-48) ng／ml] ,PTX-3 [ (1-28 ± 0-54) μg／L vs. (3-58 ± 0-52) μg／L] ,NT-proBNP [(223-23 ± 76-28) pg／ml vs.(952-75 ± 85-43) pg／ml] ,LAD ,LVEDd and LV-MI in CHF group , P＝0-001 all.Compared with good prognosis group at enrollment ,there were significant rise in serum levels of galectin-3 [ (18-52 ± 1-91) ng／ml vs.(24-63 ± 2-26) ng／ml] and PTX-3 [ (2-65 ± 0-74) μg／L vs. (3-95 ± 1-05) μg／L] in poor prognosis group , P＝0-001 both .Spearman linear correlation analysis indicated that serum galectin-3 and PTX-3 levels were significant positively correlated with major adverse cardiovascular events in CHF patients ( r＝0-608 ,0-558 , P＝0-001 both).Conclusion :Serum levels of galectin-3 ,PTX-3 and NT-proBNP levels are significant rise and closely related to prognosis of CHF patients ,can be used as auxiliary indexes predicting prognosis and may provide the basis for formulation of target therapy .

Philadelphia chromosome-negative myeloid neoplasms in patients with Philadelphia chromosome-positive chronic myeloid leukemia during tyrosine kinase inhibtor-therapy / 中华血液学杂志

Objective: To compare the clinical features between the 2 cohorts developing myelodysplastic syndrome or acute myeIogenous Ieukemia in Philadelphia chromosome-negative cells (Ph(-) MDS/AML) and maintaining disease stable in the patients with Philadelphia chromosome-positive chronic myeloid Ieukemia (Ph(+) CML) who had clonal chromosomal abnormalities in Philadelphia chromosome-negative metaphases (CCA/Ph(-)) during tyrosine kinase inhibtor (TKI) - therapy. Methods: We retrospectively analyzed Ph(+) CML patients who developed CCA/Ph(-) during TKI-therapy from May 2001 to December 2017. Results: Data of CCA/Ph(-) 63 patients, including 7 progressing to Ph(-) MDS/AML and 56 remaining disease stable were collected. Compared with those with stable disease, patients with Ph(-)MDS/AML had lower hemoglobin (P=0.007) and platelet (P=0.006) counts, and higher proportion of peripheral blasts (P<0.001) when the first time CCA/Ph(-) was detected, and more mosonomy 7 abnormality (5/7, 71.4%) when MDS or AML was diagnosed; meanwhile, trisomy 8 (32/56, 57.1%) was more common in those with stable disease. Outcome of the patients with Ph(-) MDS/AML were poor. However, most of those with CCA/Ph(-) and stable disease had optimal response on TKI-therapy. Conclusions: A few patients with Ph(+) CML developed CCA/Ph(-) during TKI-therapy, most of them had stable disease, but very few patients developed Ph(-) MDS/AML with more common occurrence of monosomy 7 or unknown cytopenia. Our data suggested the significance of monitoring of peripheral blood smear, bone marrow morphology and cytogenetic analysis once monosomy 7 or unknown cytopenia occurred.

Comparison of nilotinib vs imatinib as frontline therapy in newly diagnosed patients with chronic myeloid leukemia in chronic phase / 中华血液学杂志

Objective: To compare the cytogenetic and molecular responses, outcomes and severe hematologic toxicity of nilotinib and imatinib as frontline therapy in newly diagnosed patients with chronic myeloid leukemia in chronic phase (CML-CP) . Methods: Newly diagnosed CML-CP patients were consecutively recruited from January 2006 to December 2018 who received nilotinib and imatinib as first-line treatment. Clinical data were retrospectively analyzed. Results: A total of 524 patients were classified into 439 (83.8%) receiving imatinib and 85 (16.2%) receiving nilotinib. Comparing with imatinib group, patients in nilotinib group were much younger (P=0.019) and more with intermediate and high Sokal risks (P<0.001) , WBC ≥100×10(9)/L (P<0.001) , HGB<120 g/L (P<0.001) , blast cells in bone marrow (P=0.026) , splenomegaly (P<0.001) by physical examination at diagnosis, and longer interval from diagnosis to TKI treatment (P=0.003) . With a median TKI duration of 57 (range 3-153) months, the probabilities of complete cytogenetic response (CCyR) (P=0.011) , major molecular response (MMR) (P=0.001) and MR(4.5) (P=0.046) were much higher in nilotinib group than those in imatnib according to each risk group. There is no statistical significance on probabilities of failure free survival (FFS) , progression free survival (PFS) and overall survival (OS) at 6 years between the two groups. Multivariate analyses showed that imatinib was an adverse factor associated with achieving CCyR (OR=0.6, 95% CI 0.5-0.8, P=0.001) , MMR (OR=0.6, 95% CI 0.5-0.9, P=0.032) and MR(4.5) (OR=0.6, 95%CI 0.5-0.9, P=0.032) and poor FFS (OR=1.9, 95%CI 1.0-3.4, P=0.041) . In addition, Sokal score was an independent factor affecting cytogenetic and molecular responses, treatment failure, disease progression and survival. Male, WBC ≥100×10(9)/L or HGB<120 g/L at diagnosis were significantly associated with lower cytogenetic and molecular response rates and/or poor FFS. The severe hematologic adverse events were not associated with different TKIs. Conclusions: Nilotinib reaches to the faster and deeper cytogenetic and molecular responses and significantly improves FFS than imatinib in newly diagnosed patients with CML-CP.

Fertility and disease outcomes in patients with chronic myeloid leukemia / 中华血液学杂志

Objective: To explore Fertility and disease outcomes in patients with chronic myeloid leukemia (CML) . Methods: Clinical and fertility outcomes of male (from Jul. 1998 to Feb. 2018) and female CML (from Sep. 2009 to Feb. 2018) patients were retrospectively analyzed at Peking University People's Hospital. Results: A total of 49 male CML patients and their spouses were enrolled. Before their spouses conceived, 34 patients were receiving tyrosine kinase inhibitor (TKI) imatinib, 9 with nilotinib, and 6 with dasatinib. At the time of conception, the median age of these male patients was 32 years (range, 25-48 years) , and the median TKI treatment duration was 36 months (range, 0.2-198 months) . One male patient having achieved complete hematologic response yet discontinuing TKI for a year developed a disease progression to blast crisis. The other 48 patients sustained stable disease. The total conception times were 61 and finally 55 infants were born including one with premature birth, two with low birth weight, and one with hypospadias receiving surgery. The other 18 female patients after pregnancy were enrolled. Two patients developed spontaneous abortions. Two received induced abortions. Fourteen gave birth to healthy infants without congenital malformation. The interval from diagnosis of CML to initiation of TKI was 4 months (range, 0.3-16 months) . During a median follow-up of 45 months (range from 7-114 months) , the estimated complete cytogenetic response (CCyR) rate, major molecular response (MMR) rate and molecular response(4.5) (MR(4.5)) rate by 5 years were 88.9%, 85.3% and 35.1%, respectively. The estimated failure-free survival, progression-free survival and overall survival were 64.2%, 90.9% and 90.9%, respectively. All 14 babies developed as normal. Conclusions: It seems that TKIs do not affect pregnancy outcome in the spouses of male CML patients, suggesting that withdrawal of TKIs is not necessary. Female CML patients have good pregnancy and disease outcomes in the TKI era.

Comparison of the efficacy and safety of Chinese generic imatinib and branded imatinib in patients with chronic myeloid leukemia in consideration of demographic characteristics / 中华血液学杂志

Objectives: To compare the efficacy and safety of Chinese generic imatinib with branded imatinib as frontline therapy in adults with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) (Frontline group) , and to explore the efficacy and safety of Chinese generic imatinib in CML-CP patients switching from branded imatinib (Switching group) . Methods: Frontline group: Data of adults with newly diagnosed CML-CP receiving Chinese generic imatinib (Xinwei(®)) or branded imatinib (Glivec(®)) between October 2013 and August 2018 were retrospectively collected and analyzed. Switching group: Data of adults diagnosed with CML-CP who received branded imatinib and then switched to Chinese generic imatinib after achieving at least complete cytogenetic response (CCyR) were retrospectively collected and analyzed. Results: Frontline group: In total, 409 adult patients receiving Chinese generic imatinib (n=201) or Glivec (n=208) were included in this study. Median age was 42 years (range, 18-83 years) . Comparison of baseline showed significant difference on demographic characteristics among two cohorts: lower education level (P<0.001) , and divorced or widowed status (P=0.004) and rural household registration (P<0.001) were more common in the generic imatinib cohort than those in the Glivec cohort. There was no significant difference on age, gender, Sokal risk score, WBC and HGB between the 2 cohorts. With a median follow-up of 25 months (range, 3-62 months) , there was no significant difference on the 3-year cumulative incidence of achieving CCyR (97.5% vs 94.5%, P=0.592) , major molecular response (MMR) (84.3% vs 93.1%, P=0.208) , molecular response(4.0) (MR(4.0)) (42.7% vs 41.7%, P=0.277) , molecular response(4.5) (MR(4.5)) (25.4% vs 33.0%, P=0.306) as well as the 3-year probabilities of failure free survival (FFS) (76.7% vs 81.0%, P=0.448) , progression free survival (PFS) (91.8% vs 96.3%, P=0.325) and overall survival (OS) (95.8% vs 98.5%, P=0.167) between the generic and branded imatinib cohorts. Multivariate analysis showed the type of imatinib was not associated with treatment responses and outcomes. The incidences of adverse effects were comparable in the 2 cohorts. Switching group: In total, 39 patients switching from branded imatinib to Chinese generic imatinib after achieving at least CCyR were included in this study. Median age was 42 years (range, 23-80 years) . With a median follow-up of 39 months (range, 6-63 months) , molecular responses were maintained in 23 (58.9%) patients and improved in 12 (39.8%) patients. Adverse effects were tolerable. Conclusion: Demographic characteristics might influence the choice of the type of TKI used in CML-CP patients. There was a comparable efficacy and safety between the Chinese generic imatinib and the branded imatinib in adults with newly diagnosed CML-CP under standard management and closely monitoring. Patients could safely switch from the branded imatinib to the Chinese generic imatinib.

Observation on the efficacy of consolidation chemotherapy combined with allogeneic natural killer cell infusion in the treatment of low and moderate risk acute myeloid leukemia / 中华血液学杂志

Objective: To evaluate the efficacy of consolidation chemotherapy combined with allogeneic natural killer (NK) cell infusion in the treatment of low or intermediate-risk (LIR) acute myeloid leukemia (AML) . Methods: A cohort of 23 LIR AML patients at hematologic complete remission (CR) received NK cell transfusion combined with consolidation chemotherapy after 3 consolidation courses from January 2014 to June 2019 were reviewed. Control group cases were concurrent patients from Department of Hematology, and their gender, age, diagnosis, risk stratification of prognosis, CR and the number of courses of consolidate chemotherapy before NK cell transfusion were matched with LIR AML patients. Results: A total of 45 times of NK cells were injected into 23 LIR AML patients during 4 to 7 courses of chemotherapy. The median NK cell infusion quantity was 7.5 (6.6-8.6) ×10(9)/L, and the median survival rate of NK cells was 95.4% (93.9%-96.9%) . Among them, the median CD3(-)CD56(+) cell number was 5.0 (1.4-6.4) ×10(9)/L, accounting for 76.8% (30.8%-82.9%) ; The number of CD3(+) CD56(+) cells was 0.55 (0.24-1.74) ×10(9)/L, accounting for 8.8% (4.9%-20.9%) . Before NK cell infusion, the number of patients with positive MRD in the treatment and control groups were 9/23 (39.1%) and 19/46 (41.3%) (χ(2)=0.030, P=0.862) respectively. After NK infusion, There was no significant difference in terms of MRD that went from negative to positive between the treatment and the control groups (14.3% vs 22.2%, χ(2)=0.037, P=0.847) . In the treatment group, 66.7% (6/9) of the MRD were converted from positive to negative, which was significantly higher than that in the control group (10.5%, 2/19) (χ(2)=6.811, P=0.009) . Morphological recurrence occurred in 1 case of MRD negative in the treatment group and 2 cases of MRD positive in the control group. By the end of follow-up, the median follow-up was 35 (10-59) months, the number of patients with morphological recurrence in the treatment group was 30.4% (7/23) , which was significantly lower than that in the control group (50.2%, 24/46) (χ(2)=2.929, P=0.087) , although there was no statistically significant difference between the two groups. There was no significant difference on MRD-negative between the treatment and the control groups (43.5% vs 43.5%, χ(2)=1.045, P=0.307) . The 3-year leukemia-free survival was better in the treatment group [ (65.1±11.1) %] than that in the control group [ (50.0±7.4) %] (P=0.047) . The 3-year overall survival in the treatment and control groups were (78.1±10.2) % and (65.8±8.0) % (P=0.212) , respectively. Conclusion: The consolidation of chemotherapy combined with allogeneic NK cell infusion contributed to the further remission of patients with LMR AML and the reduction of long-term recurrence.

Severe hematologic toxicity and its impact on treatment response in newly diagnosed patients with chronic myeloid leukemia receiving tyrosine kinase-inhibitor therapy / 中华血液学杂志

Objectives: To explore the incidence and factors of severe leukopenia and/or thrombocytopenia in newly diagnosed patients with chronic myeloid leukemia (CML) to probe their impacts on cytogenetic and molecular responses, progression free survival (PFS) and overall survival (OS) . Methods: Data of newly diagnosed patients with CML in the chronic phase (CP) and/or accelerated phase (AP) were retrospectively collected and analyzed. Results: 855 CML patients [including 744 (87%) in the CP and 111 (13.0%) in the AP] were included in this study. 523 (61.2%) patients were male with a median age of 39 years (range, 14-87 years) . 749 (87.6%) patients received imatinib, 93 (10.9%) nilotinib, and 13 (1.5%) dasatinib, respectively as front-line therapy. At a median treatment of 1 month (range, 0.1-7.0 months) , 137 (16.0%) developed ≥grade 3 leukopenia and/or thrombocytopenia and recovered 0.6 month (range, 0.3-6.5 months) . Multivariate analysis showed that female gender (OR=1.5, 95%CI 1.0-2.2, P=0.033) , WBC ≥100×109/L (OR=1.9, 95%CI 1.3-2.8, P=0.001) , CP in Sokal high-risk (OR=2.2, 95%CI 1.2-3.9, P=0.005) , AP with ≥15% blast cells in blood or bone marrow (OR=5.1, 95%CI 1.9-13.3, P=0.001) were factors associated with higher incidence of ≥grade 3 leukopenia and/or thrombocytopenia. Severe leukopenia and/or thrombocytopenia with time of drug discontinuance >2 weeks was associated with lower probabilities of achieving complete cytogenetic (OR=0.4, 95%CI 0.3-0.6, P<0.001) , severe leukopenia and/or thrombocytopenia, no matter the time of drug discontinuance >2 weeks or ≤2 weeks, were associated with lower probabilities of achieving major molecular responses (OR=0.3, 95%CI 0.2-0.5, P<0.001; OR=0.7, 95%CI 0.5-1.0, P=0.036) and MR4.5 (OR=0.2, 95%CI 0.1-0.5, P=0.002; OR=0.7, 95%CI 0.4-1.1, P=0.110) ; however, those had no impacts on PFS and OS. Conclusions: Severe leukopenia and/or thrombocytopenia were common adverse events during TKI therapy. Female patients, WBC ≥100×109/L at diagnosed, CP in Sokal high-risk, CML-AP with ≥15% blast cells in blood or bone marrow were at high risk for higher incidence of severe leukopenia and/or thrombocytopenia. Those severe adverse events had impacts on lower cytogenetic and molecular response.

Clinical analysis of myeloid neoplasms with t (3;21) (q26;q22) / 中华血液学杂志

Objective: To analyze the characteristics of myeloid neoplasms with t (3;21) (q26;q22) . Methods: Clinical data of patients with t (3; 21) (q26; q22) , diagnosed as hematologic malignancies in Peking University people's hospital from January 2011 to March 2018, were collected retrospectively. 19 patients in our hospital and forty-eight patients bearing t (3;21) (q26;q22) with detailed survival data reported in literature were summarized. Kaplan- Meier method was used for survival analysis. Results: Among 19 patients, including 15 males and 4 females with a median age of 36 years (22-68 years) , 4 cases was diagnosed as de novo acute myeloid leukemia (AML) , 4 as myelodysplastic syndromes (MDS) , 3 as MDS-AML and 8 as chronic myelogenous leukemia (CML) in myeloid blast transformation. All of the 19 patients were detected to have t (3;21) (q26;q22) by G-banding technique and 13 carried additional cytogenetic aberrations. 9 of the 19 patients were detected for positive AML1-MDS1 fusion genes. In the 9 patients with detailed follow-up data, 6 patients received chemotherapy and only 2 achieved complete remission (CR) while 4 with no response. During the follow-up period, 8 patients died and the median overall survival (OS) was 6 months (4.5 to 22 months) . Survival analysis of the present 9 patients together with the literature data showed that the prognosis was poor and the median OS was 7 months. In particular, AML/t-AML had the worst prognosis. Hematopoietic stem cell transplantation (HSCT) could significantly improve survival, the median OS in HSCT group and non-HSCT group were 20.9 and 4.7 months respectively (P<0.001) . Conclusions: t (3; 21) (q26; q22) is a rare recurrent chromosomal abnormality which is detected mainly in myeloid neoplasm and confer to poor clinical prognosis. HSCT should be recommended to improve the outcomes.

Advances in research on correlation between microparticle and coronary athero-sclerosis / 中国免疫学杂志

The microparticle is a kind of small particle formed in the process of cell activation and apoptosis.Currently,the mi-croparticle is taken as the main medium of inflammatory reaction.However,it may also play a role of atherosclerotic plaque formation and subsequent onset,development and formation of acute coronary syndrome.Furthermore,the microparticle participates in the atherosclerotic plaque formation and rupture,coagulation startup and thrombus formation.Through the study of microparticle,the coronary atherosclerotic heart disease pathogenesis can be deeply understood.

Cognition of mental health and its influencing factors among residents in Yinzhou District / 预防医学

Objective To learn the awareness and influencing factors of mental health knowledge in Yinzhou District. Methods The multi-stage cluster sampling was used to investigate 1239 residents by using the questionnaire of the residents' mental health awareness. Results The total awareness rate was 61.3％, and the awareness rate that was relatively low was mainly concentrated on "World Suicide Prevention Day" (29.9％),"mental illness was a problem in mind" (32.1％),"mental illness was due to the stimulation" (44.0％) . Multiple linear regression analysis found that the residents who were older (β=0.039, P<0.05), lived in city (β=2.073, P<0.05), worked as administrators, technicians, and waiters compared with self-employed, retired and unemployed (β: -2.350 - -1.591, P <0.05) scored higher. Conclusion The residents' awareness of mental health knowledge is low. The urban residents, self-employed, workers, farmers, are the key populations to be educated with mental health system.

Application of CD138 Immunomagnetic Sorting Myeloma Cells Combined with Fluorescence in Situ Hybridization for Detecting Cytogenetic Abnormalities of Multiple Myeloma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the efficiency of direct fluorescence in situ hybridization (D-FISH) versus FISH on CD138 immunomagnetic sorting myeloma cells (MACS-FISH) to detect the cytogenetic abnormalities of multiple myeloma.</p><p><b>METHODS</b>Thirty-one patients with multiple myeloma (MM) were detected by D-FISH and MACS-FISH, using 5 probes, including 1q21, D13S319, RB1, IgH, P53. The IgH rearrangement positive patients were further examined by 3 IgH rearrangement subtype FISH probes including IgH/FGFR3, IgH/MAF and IgH/CCND1.</p><p><b>RESULTS</b>Metaphase karyotyping revealed cytogenetic abnormalities in 5 cases (16.1%), clonal aberrations were detected in 13 cases(41.9%) by D-FISH, while 25 case(80.6%) with clonal aberrations by MACS-FISH. The results between these 2 FISH methods were significantly different (P=0.042). The detection frequency of clonal aberration by each probes of D-FISH was 22.6%,25.8%,29%,38.7% and 9.7% respectively for 1q21 amplification, D13S319 deletion,RB1 deletion, IgH rearrangement and P53 deletion, compared with 48.4%,45.2%,48.4%,67.7% and 16.1% respectively by MACS-FISH. The 2 FISH methods were well consistent when the percentage of plasma cells was ≥20% in bone marrow smears. When the percentage of plasma cells was<20% in bone marrow smears, the difference between these 2 methods was very statistically significant (P=0.00).</p><p><b>CONCLUSION</b>MACS-FISH can obviously improve the detection efficiency of cytogenetic abnormalities in patients with MM. Conventional cytogenetics combined with MACS-FISH is an ideal efficient method to detect the cytogenetic abnormalities in MM patients, and should be applied widely, especially for those patients with the plasma cells <20% in bone marrow smears.</p>