Red blood cell lifespan detected by endogenous carbon monoxide breath test in patients with polycythemia vera / 中华内科杂志

Objective@#To detect the red blood cell lifespan in patients with polycythemia vera (PV), and explore the influencing factors.@*Methods@#From February 2017 to December 2018, 27 patients with PV at Blood Diseases Hospital, Chinese Academy of Medical Science and 18 normal controls were recruited. Red blood cell lifespan was detected by endogenous carbon monoxide (CO) breath test. The related factors were analyzed.@*Results@#The average red blood cell lifespan of 27 PV patients was 80 (range, 35-120) days (d), which was significantly shorter than that of the normal controls [110.5(69-166) d, P<0.05], namely 35.3 d shorter. The red blood cell lifespan of ten newly diagnosed patients and 17 patients who were treated with hydroxyurea and/or interferon were 98 (35-117) d and 69 (45-120) d, respectively, which were both shorter than that of the normal control (P=0.010, 0.000). Correlation analysis showed that red blood cell lifespan of patients with newly diagnosed PV was associated with JAK2 mutation allele burden (r=0.900, P=0.037), peripheral blood lymphocyte count (r=-0.742, P=0.014) and the level of serum vitamin B12 (r=-0.821, P=0.023).@*Conclusion@#The lifespan of red blood cells in patients with PV is about one-third shorter than normal, and is related to JAK2 mutation allele burden, absolute lymphocyte count, and serum vitamin B12 level.

Red blood cell lifespan detected by endogenous carbon monoxide breath test in patients with polycythemia vera / 中华内科杂志

Objective To detect the red blood cell lifespan in patients with polycythemia vera (PV), and explore the influencing factors. Methods From February 2017 to December 2018, 27 patients with PV at Blood Diseases Hospital, Chinese Academy of Medical Science and 18 normal controls were recruited. Red blood cell lifespan was detected by endogenous carbon monoxide (CO) breath test. The related factors were analyzed. Results The average red blood cell lifespan of 27 PV patients was 80 (range, 35-120) days (d), which was significantly shorter than that of the normal controls [110.5(69-166) d, P<0.05], namely 35.3 d shorter. The red blood cell lifespan of ten newly diagnosed patients and 17 patients who were treated with hydroxyurea and/or interferon were 98 (35-117) d and 69 (45-120) d, respectively, which were both shorter than that of the normal control (P=0.010, 0.000). Correlation analysis showed that red blood cell lifespan of patients with newly diagnosed PV was associated with JAK2 mutation allele burden (r=0.900, P=0.037), peripheral blood lymphocyte count (r=-0.742, P=0.014) and the level of serum vitamin B12 (r=-0.821, P=0.023). Conclusion The lifespan of red blood cells in patients with PV is about one?third shorter than normal, and is related to JAK2 mutation allele burden, absolute lymphocyte count, and serum vitamin B12 level.

TheMRIevaluationandriskfactorsanalysisofchronicinjuryof medialcollateralligamentinpatientswithosteoarthritis / 实用放射学杂志

Objective Toexploretheriskfactorsofchronicinjuryofmedialcollateralligament(MCL)inpatientswithosteoarthritis(OA). Methods Thestudywasconductedretrospectivelyandatotalof191patientsinourhospitalfromFebruary2017toApril2018were collected,amongthem,86casesofOApatientswithchronicinjuryofMCLastheobservationgroup,42casesofpatientswithacute MCLinjurycausedbytraumaasthecontrolgroup1,63casesofOApatientswithoutMCLinjuryascontrolgroup2.TheMRImanifestationsof kneejointsintheobservationgroupandthecontrolgroup1werecompared,thedifferencesofthedamagemechanismsbetweenthe twogroupswereanalyzed.TheMRImanifestationsandrelatedclinicaldataoftheobservationgroupandthecontrolgroup2wereanalyzed,and thefactorsthatmightcausethechronicinjuryofMCL wereidentifiedbyunivariateregressionanalysis,thenwereincludedinthe non-conditional L o g istic regression m odel for m ultivariate analysis and the risk factors and protective factors of chronic injury of MCLwerefinallyscreenedout.Results Thedifferencesinthe MRImanifestationsbetweentheobservationgroupandthecontrol group1,includingthegradingoftheMCLinjury,thegradingandthedislocationofmedialmeniscus,thedistributionofbonemarrow edema,theanteriorandposteriorcruciateligamentinjuriesandthestenosistypesofthejointspacewerestatisticallysignificant(P<0.05).The resultsrevealedthatthechronicinjuryofMCLwasrelatedtoage,sex,medialmeniscusdislocation,thegradingofmedialmeniscus, osteophyte,anteriorcruciateligamentinjury,posteriorcruciateligamentinjury,andthestenosistypeofthejointspaceusingtheunivariateanalysis (P<0.05).Theresultsrevealedthatosteophyte(OR=38.231,95%CI:6.573-222.370),medialmeniscusdislocation (OR=6.504, 95%CI:1.508-28.046),anteriorcruciateligamentinjury(OR=7.236,95%CI:1.188-44.090)wereriskfactorsforchronicinjury ofMCLinOApatientsandlateraljointspacestenosis(OR=0.014, 95%CI:0.002-0.092)andpatella-femoraljointspacestenosis (OR=0.006,95%CI:0.000-0.071)wereprotectivefactorsusing multiple L o g istic regression model.Conclusion Thepathogenicfactorsaredifferentbetweenchronicinjuryof MCLin OA patients andacuteinjuryofMCL.Osteophyte,medialmeniscusdislocation,anteriorcruciateligamentinjuryareriskfactorsforchronicinjury ofMCLinOApatients,andlateraljointspacestenosisandpatella-femoralspacestenosisareprotectivefactors.

The effects of serum potassium on insulin secretion ability in patients with impaired glucose regulation / 中华内分泌外科杂志

Objective To explore whether serum potassium can influence insulin secretion ability in pa tients with impaired glucose regulation (IGR).Methods 320 subjects with IGR were enrolled in our study.All subjects underwent a standard OGTT.Their clinical and biochemical parameters were measured.Insulin secretion indices were measured by DI0,DI30,and DI120.Results In IGR,DI0 was negatively correlated with BMI (r=-0.122,P=0.015),total cholesterol (TC) (r=-0.182,P=0.032),low density lipoprotein-cholesterol (LDL-C) (r=-0.1 78,P=0.026) and triglyceride (TG) (r=-0.179,P=0.01 1).DI30 was negatively correlated with TC (r=-0.146,P=0.001),TG(r=-0.192,P=0.027)and LDL-C(r=-0.134,P=0.014).DI120 was negatively correlated with TC(r=-0.222,P＜ 0.001),TG(r=-0.209,P＜0.001)and LDL-C (r=-0.183,P＜0.001) while postively correlated with serum potassium (r=0.208,P＜0.001).The multiple regression model analysis showed that serum potassium (β=0.380,P＜0.001) was independently correlated to DI120.Conclusion In patients with IGR,serum potassium is associated with insulin secretion ability,which may provide a new treatment strategy for preventing IGR into T2DM.

The clinical and laboratory characteristics of congenital pyruvate kinase deficiency / 中华内科杂志

Clinical data of 19 patients with congenital pyruvate kinase deficiency were analyzed. Insufficient pyruvate kinase confirmed the diagnosis. Laboratory parameters of hemolysis were summarized. In cases of neonatal hyperbilirubinemia and unexplained hemolytic anemia, pyruvate kinase activity and next generation sequencing test may help the early diagnosis.

The characteristic of hereditary spherocytosis related gene mutation in 37 Chinese hereditary spherocytisis patients / 中华血液学杂志

Objective@#To reveal the genetic characteristics of erythrocyte membrane protein in hereditary spherocytosis (HS) in China.@*Methods@#Next-generation sequencing technology was used to detect mutations in genes of erythrocyte membrane proteins in 51 clinically diagnosed HS patients. The relationship between gene mutations and clinical phenotypes was analyzed.@*Results@#Mutations in erythrocyte membrane protein genes were detected in 37 patients, including 17 with ANK1 mutations (17/37, 45.9%), 14 with SPTB mutations (14/37, 37.8%), and 5 with SLC4A1 mutations (5/37, 13.5%). One patient carried both heterozygous ANK1 mutation and SPTB mutation (1/37, 2.7%). SPTA1 and EPB42 mutation was not fou nd in any patient. Nonsense mutations (36.8%) and missense mutations (31.6%) were most common. Of the 38 mutations detected, 34 were novel mutations and have not been reported elsewhere (89.5%). Sixteen HS patients underwent parental genetic validation, 6 patients (37.5%) inherited gene mutation from parents and 10 (62.5%) were de novo. The peripheral blood cell parameters of HS patients were not related to the mutant genes and gene mutation types. However, it seems that HS patients with mild clinical status are prone to carry SPTB mutations while more patients with severe clinical status have ANK1 mutations.@*Conclusions@#ANK1 and SPTB are the most common mutant genes in Chinese HS patients, mainly with missense mutations and nonsense mutations. There was no significant correlation between the mutation of HS related genes and the severity of HS.

Using target next-generation sequencing assay in diagnosing of 46 patients with suspected congenital anemias / 中华血液学杂志

Objective@#To evaluate the impact of the targeted next-generation sequencing (NGS) assay for difficult congenital anemias.@*Methods@#Blood Disease Hospital Anemia Panel 2014 (BDHAP-2014) including 217 known genes of congenital anemias was developed. NGS and parental verification were performed for patients who were suspected diagnosed with congenital anaemia from August 2014 to July 2017.@*Results@#A total of 46 patients were enrolled in this study, the clinical suspection were 11 cases Fanconi anemia (FA), 8 cases congenital dyserythropoietic anemia (CDA), 6 cases congenital sideroblast anemia (CSA), 12 cases congenital hemolytic anemia (CHA), 1 case dyskeratosis congenital (DC), 4 cases iron-refractory iron deficiency anemia and 4 cases unexplained cytopenia (Uc), respectively. 28 (60.9%) of 46 patients became confirmed cases after targeted NGS, corresponding to 44 mutations of which 33 were new. 26(56.5%) patients with results of the assay matching to clinical suspection, including FA (5/11, 45.5%), CSA (6/6, 100.0%), CDA (3/8, 37.5%) and CHA (12/12, 100.0%). 2 (4.3%) cases not matching to clinical suspection, including dyskeratosis congenital (DC) was made in 1(2.2%) patients with suspected FA and familial hemophagocytic lymphohistiocytosis (FHL) was made in 1(2.2%) patients with suspected unexplained cytopenia (Uc). In 12 CHA patients, the hemolytic type was further clarified by the NGS. The remaining 18 cases were not clearly diagnosed.@*Conclusion@#Targeted NGS assay is of major impact on congenital anemias. The assay should be used routinely in congenital anemias.

The life span of red blood cell in patients with severe/very severe aplastic anemia / 中华血液学杂志

Objective@#To explore the life span of red blood cells (RBC) in patients with severe/very severe aplastic anemia (SAA/VSAA).@*Methods@#Clinical data of 128 SAA/VSAA patients from November 2016 to April 2017 were retrospectively analyzed, and 13 healthy volunteers in the same period was used as normal control. The endogenous Breath Carbon Monoxide (CO) test was used to detect the life span of RBC in SAA/VSAA patients, and the effect of immunosuppressive therapy (IST) on the life span of RBC in these patients was explored.@*Results@#The mean life span of RBC in 51 untreated SAA/VSAA patients was (50.69±21.43) d, which was significantly shorter than that in normal controls[(111.85±31.55) d](t=-6.611, P<0.001). The mean life span of RBC in 77 patients treated with IST was (87.14±39.28) d. The mean life span of RBC in complete responses (CR), hematologic response (HR) and non-response (NR) patients were (106.15±32.12) d, (92.00±38.60) d and (50.44±21.56) d, respectively. The life span of RBC in patients with HR was significantly longer than that in newly diagnosed and NR patients (t=7.430, P<0.001; t=4.846, P=0.002), which was similar to that in the normal controls (t=-1.743,P=0.085). There was no statistical significance between CR patients and the normal controls in the mean life span of RBC (t=-0.558, P=0.579). No factor affecting the RBC life span was found in univariate logistical regression analyses in the newly diagnosed SAA/VSAA patients. The serum levels of IL-2R and IL-6 were much lower in HR patients than NR patients[IL-2R: 4.3×105 U/L vs 6.5×105 U/L, z=-2.733, P=0.006; IL-6: 2.6 (2.0-17.7) ng/L vs 6.1 (2.0-14.4) ng/L, z=-2.968, P=0.003]. Of the 51 newly diagnosed patients, 38 received IST and their 3-month curative effect was evaluated. Receiver operator characteristics (ROC) curve was used to analyze the predictive effect of RBC life span of untreated patients on the efficacy of IST before treatment. The cut-off point was 60 days with sensitivity of 37.5% and specificity of 86.4%. In 9 cases with life span of RBC>60 d before IST, 6 cases acquired HR, while in 29 cases with life span of RBC ≤ 60 d before IST, 10 cases acquired HR, the difference was not statistically significant (P=0.128).@*Conclusion@#The life span of RBC in SAA/VSAA patients was shortened, which can be improved even recovered to the normal after IST. Elevated cytokines might play a role in the pathophysiology of the shortened RBC life span in SAA/VSAA.

Clinical effects of calcium dobesilate combined with insulin in the treatment of elderly patients with diabetic nephropathy in early stage / 中国基层医药

Objective To investigate the clinical effects of calcium dobesilate combined with insulin in the treatment of elderly patients with diabetic nephropathy in early stage.Methods 100 elderly patients with diabetic nephropathy in early stage were chosen,and they were randomly divided into two groups according to the digital table,each group in 50cases.The control group were given benazepril alone,and the observation group were given benazepril combined with calcium dobesilate on the basis of intensive insulin intervention.The levels of FPG,2hPG,Scr,BUN,mAlb,β2-MG,Cys-C and hs-CRP and QOL-C30 scores before and after treatment of the two groups were compared.Results There were no statistically significant differences in the levels of FPG,2hPG after treatment between the two groups(all P ＞0.05).Before treatment,the levels of Scr,BUN,mAlb and β2-MG of the control group were (81.16 ± 18.92) mmol/L,(5.63 ± 1.15) mmol/L,(105.71 ± 21.77) mg/24h,(543.46 ± 74.70) μg/L,respectively,which of the observation group were (81.59 ± 19.04) mmol/L,(5.58 ± 1.13) mmol/L,(106.33 ± 2 L 82) mg/24h,(548.20 ± 75.37) μg/L,respectively.After treatment,the levels of Scr,BUN,mAlb and β2-MG of the control group were (78.35 ± 14.35) mmol/L,(5.17 ± 0.97) mmol/L,(69.84 ± 14.24) mg/24h,(395.56 ±42.38) μg/L,respectively,which of the observation group were (73.10 ± 10.74) mmol/L,(4.63 ± 0.71) mmol/L,(52.92 ± 10.52) mg/24h,(337.89 ± 25.04) μg/L,respectively.The levels of Scr,BUN,mAlb and 32-MG after treatment of the observation group were significantly lower than those of the control group and before treatment (t =2.45,2.66,2.18.2.40;2.82,3.10,2.58.3.34;2.61,3.20;2.66.3.05;all P ＜ 0.05).Before treatment,the levels of Cys-C and hs-CRP of the control group were (1.82 ± 0.67) mg/L,(22.73 ± 6.54) mg/L,respectively,which of the observation group were (1.87 ± 0.70) mg/L,(1.17 ± 0.27) mg/L,respectively.After treatment,the levels of Cys -C and hs-CRP of the control group were (1.59 ± O.50) mg/L,(19.35 ± 5.60) mg,/L,respectively,which of the observation group were (22.58 ± 6.50) mg/L,(15.88 ± 4.03) mg/L,respectively.The levels of Cys-C and hs-CRP after treatment of the observation group were significantly lower than those of the control group and before treatment (t =2.32,2.67;2.85,3.19,2.66,3.02;all P ＜ 0.05).The QOL-C30 scores of the control group before and after treatment were (52.65 ± 7.70) points,(68.29 ± 9.84) points,respectively.The QOL-C30 scores of the observation group before and after treatment were (53.22 ± 7.78)points,(80.53 ± 12.10)points,respectively.The QOL-C30 scores of the observation group after treatment were significantly higher than those of the control group and before treatment (t =2.38,2.78,3.15,all P ＜ 0.05).Conclusion Bigeminy drug regimen assisted with intensive insulin intervention in the treatment of elderly patients with diabetic nephropathy in early stage can efficiently protect renal function,reduce the levels of inflammatory cytokines and is helpful to improve the quality of life.

Evaluation of efficacy of immunosuppressive therapy plus recombinant human thrombopoietin for children with severe aplastic anemia / 中华儿科杂志

Objective@#To evaluate the therapeutic efficacy and safety of immunosuppressive therapy (IST) combined with recombinant human thrombopoietin (rhTPO) for severe aplastic anemia (SAA) in pediatric patients.@*Method@#A retrospective case-control study was conducted and the clinical data of 45 pediatric patients with de novo SAA admitted to the Anemia Diagnosis and Treatment Center of Chinese Academy of Medical Sciences & Blood Disease Hospital during the period from December 2009 to December 2014 were analyzed. Among them, 15 patients were treated with the regimen of IST together with rhTPO and 30 patients were given IST treatment only. The variation characteristics of the peripheral blood routine as well as the transfusion of blood products was dynamically observed, and the therapeutic efficacy was assessed respectively after 3, 6 and 12 months after the treatment. In the meantime, adverse effects related to rhTPO application were recorded. Thereafter, the statistics of the two groups were compared by non-parametric rank sum test.@*Result@#Among 45 pediatric patients, there were 26 male and 19 female, and the median age was 11 years (6-14). The number of patients received good hematological response(complete remission (CR) plus good partial response (GPR)) in the combinatory group versus vs. the IST group was 6 vs. 3 patients (χ2=3.906, P=0.048) at the 3rd month, 7 vs. 7 patients (χ2=1.568, P=0.210) at the 6th month, and 13 vs. 14 patients (χ2=6.667, P=0.01) at the 12th month respectively. For those achieved good hematological response at the 3rd month, the amount of platelets transfusion and red blood cells transfusion of the combined group were both less than that of the IST group during the period from the 10th to the 12th weeks (platelets transfusion: 1.4 U vs. 2.9 U, t=-3.523, P=0.002; red blood cells transfusion: 0.8 U vs. 2.6 U, t=-2.392, P=0.026). No serious adverse effect related to rhTPO application was observed in the IST combined with rhTPO group.@*Conclusion@#Application of rhTPO can improve the short-term therapeutic efficacy of IST for pediatric SAA, alleviate transfusion dependence, and has a good safety profile.

Correlation of the degree of band 3 protein absence on erythrocyte membrane by eosin-5′-maleimide binding test and clinical phenotype in hereditary spherocytosis / 中华血液学杂志

Objective@#To investigate the relationship between the eosin-5′-maleimide (EMA) binding test and the clinical severity of hereditary spherocytosis (HS).@*Methods@#A total of 258 un-splenectomize HS patients were consecutively enrolled. Correlation of hemoglobin concentration, hemolytic parameters, compensating erythropoiesis and the EMA binding test were evaluated.@*Results@#258 (128 male and 130 female) patients were included in this study, including 91 compensatory hemolysis patients, 53 patients with mild anemia, 78 patients with moderate anemia and 36 patients with severe anemia. The median age at diagnosis was 23 (2-70) years. The median decreased fluorescence intensity of EMA binding test was 29.97% (16.09%-47.34%) and the average intensity was (29.70±6.28) % of 258 HS patients. The decreased EMA binding fluorescence intensity correlated with MCV (r=-0.343, P<0.001) and MCHC (r=0.223, P<0.001). There was no relationship between EMA fluorescence intensity and absolute reticulocyte count (r=0.080, P=0.198) , reticulocyte percentile (r=-0.015, P=0.813) , IBIL levels (r=-0.009, P=0.902) , HGB levels (r=-0.067, P=0.280). Evaluated as a quartile variable, EMA fluorescence intensity was not correlated with anemia severity (C=0.150, P=0.746).@*Conclusion@#EMA binding test does not related to anemia levels and has no major clinical implications for disease severity in HS.

Effects of pre-immunosupressive therapy iron overload on hematologic response of severe aplastic anemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the effects of serum ferritin (SF) and iron overload (IO) pre-immunosupressive treatment (IST) on hematologic response of severe aplastic anemia (SAA/VSAA) patients treated with IST.</p><p><b>METHODS</b>257 SAA/VSAA patients who underwent first-line IST from Feb, 2003 to Dec, 2011 in Anemia Therapeutic Centre, Institute of Hematology and Blood Diseases Hospital were retrospectively analyzed, the status of SF before IST and the IO-affected factors were studied. The effects of IO on hematologic response of SAA/VSAA patients were evaluated as well.</p><p><b>RESULTS</b>The median level of SF of 257 patients was 387 (6-2 004) μg/L. 36 patients (14%) had IO, including 20 SAA and 16 VSAA patients. According to univariate logistical regression analyses, IO was influenced by age>14 years (P=0.010) and blood transfusion (P<0.001). The multivariate logistic regression analysis showed that blood transfusion [P=0.001, OR=0.218 (95% CI 0.092-0.520)] was the only independent prognostic factor. SAA (but not for VSAA) patients with IO had much lower hematologic response rate in 6 month after IST (P=0.037). Absolute reticulocyte count and IO correlated with response at 6 month by univariate logistical regression analysis (P=0.014, 0.037). The multivariate logistic regression analysis showed that IO [P=0.021, OR=4.092 (95% CI 1.235-13.563)], ARC ≥20×10(9)/L [P=0.040, OR=2.743 (95% CI 1.049-7.175)] were independent prognostic factors.</p><p><b>CONCLUSION</b>84.8% patients had high serum ferritin before IST, and 14.0% reached IO. Adult and more blood transfusion caused IO more likely. IO correlated with response at 6 month, and was independent prognostic factor.</p>

Outcomes of very severe aplastic anemia patients with different absolute neutrophil counts after frontline immnunosuppressive therapy / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze early hematopoietic response and long-term survival of very severe aplastic anemia (VSAA) patients with different absolute neutrophil counts (ANC) after frontline immnunosuppressive therapy (IST).</p><p><b>METHODS</b>Clinical data and outcome of 145 VSAA patients treated with rabbit antithymocyte globulin combined with cyclosporine were retrospectively analyzed. Hematopoietic responses to IST and long-term survival were statistically analyzed for VSAA patients in different ANC subgroups.</p><p><b>RESULTS</b>Pre-IST ANC=0.05×10(9)/L acted as the best cutoff level to predict IST response at 3, 6 months. For 145 VSAA patients, early death rate was 13.4% (11/82) vs 1.6% (1/63), respectively, in the ANC≤0.05×10(9)/L group and ANC>0.05×10(9)/L group (P<0.05). Hematopoietic response rates to IST was 22.0% vs 54.0% (P=0.000) at 3 months, 34.1% vs 63.5% (P=0.000) at 6 months; the overall five-year survival rate was only (62.5±5.4) % vs (91.4±3.7) % (P=0.000) and five-year event-free survival rate was (42.3±5.5) % vs (63.1±6.5) % (P=0.003), respectively, in the ANC≤0.05×10(9)/L group and ANC>0.05×10(9)/L group.</p><p><b>CONCLUSION</b>VSAA patients with extremely low ANC (≤0.05×10(9)/L) had high early death rate and with very low response rate to frontline IST and poor survival, so it is urgent to seek for the alternative frontline therapy that will bring faster and better outcome for these patients.</p>

The study of genetic instability in patients with Dyskeratosis congenital / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the genetic instability in patients with Dyskeration congenita.</p><p><b>METHODS</b>The spontaneous chromosome instability of lymphocytes from 4 DC patients, 29 FA patients and 24 healthy volunteers was assessed with comet assay. The percent of DNA in comet head (HeadDNA%）, the percent of DNA in comet tail (TailDNA%）, tail moment (TM), olive tail moment (OTM), the comet cell percentage (CCP) were compared between groups. And the results of MMC test, PNH clones and karotype were analysed additionally. The correlation between TM, OTM, CCP and the severity degree of bone marrow failure in DC group were evaluated.</p><p><b>RESULTS</b>①PNH clones and karotype abnormalities were not found in 4 DC patients. ②TM (6.77 ± 0.90), OTM（6.19 ± 0.80) and CCP [(46.00 ± 5.03) %] in DC were significantly higher than those in normal control group [0.61 ± 0.49, 0.66 ± 0.42, (5.91 ± 3.19)%, P<0.05], however, not distinguished from FA patients [7.81 ± 3.58, 6.65 ± 2.21, (56.03 ± 13.47) %, P ≥ 0.05]. The aberrant cell percent at the MMC concentration of 80 μg/L in DC group was significantly lower than that in FA group [(21.00 ± 3.16) % vs (31.97 ± 6.33)%, P=0.003]. ③The correlation between TM, OTM, CCP and the severity of bone marrow failure in DC group were not found (P>0.05).</p><p><b>CONCLUSION</b>DC patients were of significantly increased genetic instability and normal DNA repair, which was different from that in FA patients. And there was no correlation between the degree of genetic instability and the severity of bone marrow failure in DC patients presenting as aplastic anemia.</p>

Chronic natural killer cell lymphocytosis: eight cases report and literature review / 中华血液学杂志

<p><b>OBJECTIVE</b>To identify the characteristics of chronic natural killer cell lymphocytosis (CNKL).</p><p><b>METHODS</b>The clinical data of eight cases defined by the World Health Organization classification was retrospectively analyzed and related literatures were reviewed.</p><p><b>RESULTS</b>Half of the 8 patients were asymptomatic. Among them, the most common abnormalities were leukocytosis with the median of 11.8(4.5-20.0)×10⁹/L and high proportion of lymphocytes [0.78(0.51-0.89)], while anemia and thrombocytopenia only in 1 patient respectively. The absolute CD3⁻CD16⁺ NK cell count with the median of 5.7(2.4-9.6)×10⁹/L increased in peripheral blood. By the end of follow-up, except one case was lost, the other seven patients were in stable condition,including four cases without any medications and three patients receiving chlorambucil or glucocorticoid.</p><p><b>CONCLUSION</b>As an indolent chronic lymphoproliferative disease, CNKL was presented with mild clinical symptoms and increased number of CD3⁻CD16⁺ NK cells in peripheral blood. Patients with symptoms could be treated with immunosuppressive therapy while those asymptomatic could be followed up without intervention.</p>

Increasing peripheral blood neutrophils after G-CSF treatment is a predictor of early response to immunosuppressive therapy in severe aplastic anemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To testify whether absolute neutrophil count (ANC) response to preimmunosuppressive-therapy (pre-IST) granulocyte-stimulating factor (G-CSF) treatment could predict early response to IST in severe aplastic anemia (SAA).</p><p><b>METHODS</b>Clinical data and hematologic response of 125 SAA patients treated with antithymocyte globulin (r-ATG) combined with cyclosporine were retrospectively analyzed. Correlation of ANC response to pre-IST G-CSF treatment and early response to IST were statistically analyzed, and receiver operating characteristic (ROC) curve was used to estimate the value of increased ANC (∆ANC) in predicting early IST response.</p><p><b>RESULTS</b>The hematologic response (HR) rate to IST in ANC reponded patients was significantly higher than non-responded group (3-month HR 49.0% vs 28.9%, P=0.023; 6-month HR 61.2% vs 40.8%, P=0.026). With ∆ANC≥0.5×10⁹/L as cutoff level, the best point to predict early IST response was 10 days after G-CSF (d 10). Response of ANC to pre-IST G-CSF treatment at d 10 was among the independent factors of predicting 3-month (P=0.004), but not for 6-month response to IST. The overall 5-year survival rate was 92.8% and 69.5% in ANC responded and non-responed groups, respectively (P=0.025).</p><p><b>CONCLUSION</b>Responding to pre-IST G-CSF treatment reflected the residual bone marrow hematopoiesis, and could act as a convenient and practical predictor to early IST response as well as long-term survival in SAA.</p>

Residual hematopoiesis is an important prognostic factor of immunosuppressive therapy in severe aplastic anemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the prognostic value of residual bone marrow hematopoiesis in severe aplastic anemia (SAA) patients with immunosuppressive therapy (IST).</p><p><b>METHODS</b>Clinical data and hematologic responses of 38 SAA patients treated with IST regimen (antithymocyte globulin combined with cyclosporine) in our hospital were retrospectively analyzed. Correlation of pre-IST baseline reticulocyte (Ret), absolute neutrophils count (ANC), soluble transferrin receptor (sTfR) concentration, corrected TPO value and hematologic response rate were statistically analyzed and receiver operating characteristic (ROC) curve was used to estimate the value of Ret, ANC, sTfR, and corrected TPO in predicting early IST response.</p><p><b>RESULTS</b>Responders to IST had significantly higher pre-IST baseline Ret, ANC, sTfR concentration [19.9(2.7-84.4)×10⁹/L, 0.59(0.12-2.67)×10⁹/L, 0.82(0.22-1.58) mg/L] and lower corrected TPO value [142.9(31.8-1 035.0)] than non-responders [5.1(1.5-23.1)×10⁹/L, 0.20(0.04-1.33)×10⁹/L, 0.45(0.19-0.72)mg/L and 2 335.0(1 308.3-7 771.2)](P<0.05). Optimizing parameter cutoff levels obtained from ROC curve was Ret 6.75×109/L, ANC 0.30×109/L, sTfR 0.76 mg/L and corrected TPO 148.6, respectively. Combining the four parameters to predict 6 month hemotologic response showed that all the 7 patients with high Ret, ANC, sTfR and low corrected TPO, while only 1 among those 9 with low Ret, ANC, sTfR and high corrected TPO.</p><p><b>CONCLUSION</b>Such parameters evaluating residual bone marrow hematopoiesis as Ret, ANC, sTfR, corrected TPO are practical in predicting early IST response in SAA.</p>

Identification and characterization of clinical features and gene mutation in a patient with iron refractory iron deficiency anemia (IRIDA) / 中华血液学杂志

<p><b>OBJECTIVE</b>To report the clinical data of a case of iron-refractory iron deficiency anemia (IRIDA), so as to improve the understanding of IRIDA.</p><p><b>METHODS</b>The IRIDA patient's hematological characteristics were summarized and analyzed. The hepcidin levels were tested by ELISA kit. The TMPRSS6 gene was amplified by PCR reaction and its mutation was analyzed by sequencing. The effect of TMPRSS6 gene mutation on TMPRSS6 protein tertiary structure was predicted by Swiss-Model.</p><p><b>RESULTS</b>The patient was characterized by typical microcytic hypochromic anemia, low transferrin saturation, more reduction of intracellular iron than exocellular iron. The plasma hepcidin level was 213.77 μg/L which was significantly higher than that of IDA patients [5.19(3.31-12.02) μg/L]. The patient also carried a homozygous missense mutation of K253E in exon 7 of TMPRSS6.</p><p><b>CONCLUSION</b>In children and younger IDA patients with no reason for iron deficiency but unresponsiveness to routine iron treatment, the diagnosis of IRIDA needs to be considered. Serum hepcidin level and TMPRSS6 gene mutation should be detected.</p>

The shift of clinic medical qualified personnel cultivation and its embodiment in higher medical curriculum reform / 中华医学教育探索杂志

Facing the diverse social environment and development, several aspects of higher clinic medical education,such as educational philosophy,personnel cultivating goal and mode,are undertaking all kinds of shift,which can be embodied in the medical curriculum reform.