Objective:To establish a rapid method for urinary iodine determination based on arsenic-cerium catalytic spectrophotometry using semiconductor water bath rapid cooling digestion technology (rapid cooling method) and an automated iodine analyzer.Methods:Urine samples were collected from three staff members randomly selected at the Gansu Provincial Center for Disease Control and Prevention. The samples were mixed and divided into three equal portions. Using rapid cooling method instead of traditional natural cooling method, the mixed urine sample was lowered from 100 ℃ to the measurement temperature (30 ℃), and then the urine iodine was determined by arsenic cerium catalytic spectrophotometry using a fully automatic iodine analyzer. The differences between the two cooling methods were compared. Additionally, the rapid cooling-arsenic-cerium catalytic spectrophotometry method was validated in terms of the linear equation of the standard curve, precision, accuracy (using urinary iodine reference materials GBW09110e and GBW09109m, and spike recovery experiments), and detection limit.Results:Using the rapid cooling method, the temperature of urine samples reached 30 ℃ in 40 minutes, while the natural cooling method required 120 minutes to reach the same temperature. Urinary iodine levels determined by the rapid cooling method in the three samples were (158.3 ± 1.9), (133.7 ± 2.7), and (219.2 ± 3.1) μg/L, respectively, while those determined by the natural cooling method were (155.5 ± 2.7), (136.2 ± 2.3), and (215.1 ± 3.9) μg/L, respectively. There was no statistically significant difference between the results of the two methods ( t = 1.43, P = 0.192). In the validation experiments for the rapid cooling method, the linear equations for the low-concentration (0 - 300 μg/L) and high-concentration (300 - 1 200 μg/L) iodine standard series were y = - 0.003 0 x + 0.117 5 ( r = - 0.999 7) and y = - 0.001 5 x + 0.649 3 ( r = - 0.999 8), respectively. The precision experiments showed that the relative deviation values of the repeated tests for two different iodine concentrations (300 and 600 μg/L) were 1.99% and 1.90%, respectively. The accuracy experiments demonstrated that the repeated test results for the national urinary iodine reference materials (GBW09110e and GBW09109m) were 216.8 and 134.7 μg/L, respectively, with relative standard deviations of 1.04% and 1.35%, respectively, all within the reference ranges[(218 ± 15) and (135 ± 10) μg/L]. The detection limit was 1.20 μg/L. The spike recovery rate ranged from 92.90% to 99.10%, with an average recovery rate of 96.77%. Conclusions:The rapid cooling-arsenic-cerium catalytic spectrophotometry method not only shortens the time required for urinary iodine determination and improves the speed of measurement, but also provides accurate results, which can be applied when a large number of urine samples need to be measured in a short period of time.

Objective:To establish a rapid method for urinary iodine determination based on arsenic-cerium catalytic spectrophotometry using semiconductor water bath rapid cooling digestion technology (rapid cooling method) and an automated iodine analyzer.Methods:Urine samples were collected from three staff members randomly selected at the Gansu Provincial Center for Disease Control and Prevention. The samples were mixed and divided into three equal portions. Using rapid cooling method instead of traditional natural cooling method, the mixed urine sample was lowered from 100 ℃ to the measurement temperature (30 ℃), and then the urine iodine was determined by arsenic cerium catalytic spectrophotometry using a fully automatic iodine analyzer. The differences between the two cooling methods were compared. Additionally, the rapid cooling-arsenic-cerium catalytic spectrophotometry method was validated in terms of the linear equation of the standard curve, precision, accuracy (using urinary iodine reference materials GBW09110e and GBW09109m, and spike recovery experiments), and detection limit.Results:Using the rapid cooling method, the temperature of urine samples reached 30 ℃ in 40 minutes, while the natural cooling method required 120 minutes to reach the same temperature. Urinary iodine levels determined by the rapid cooling method in the three samples were (158.3 ± 1.9), (133.7 ± 2.7), and (219.2 ± 3.1) μg/L, respectively, while those determined by the natural cooling method were (155.5 ± 2.7), (136.2 ± 2.3), and (215.1 ± 3.9) μg/L, respectively. There was no statistically significant difference between the results of the two methods ( t = 1.43, P = 0.192). In the validation experiments for the rapid cooling method, the linear equations for the low-concentration (0 - 300 μg/L) and high-concentration (300 - 1 200 μg/L) iodine standard series were y = - 0.003 0 x + 0.117 5 ( r = - 0.999 7) and y = - 0.001 5 x + 0.649 3 ( r = - 0.999 8), respectively. The precision experiments showed that the relative deviation values of the repeated tests for two different iodine concentrations (300 and 600 μg/L) were 1.99% and 1.90%, respectively. The accuracy experiments demonstrated that the repeated test results for the national urinary iodine reference materials (GBW09110e and GBW09109m) were 216.8 and 134.7 μg/L, respectively, with relative standard deviations of 1.04% and 1.35%, respectively, all within the reference ranges[(218 ± 15) and (135 ± 10) μg/L]. The detection limit was 1.20 μg/L. The spike recovery rate ranged from 92.90% to 99.10%, with an average recovery rate of 96.77%. Conclusions:The rapid cooling-arsenic-cerium catalytic spectrophotometry method not only shortens the time required for urinary iodine determination and improves the speed of measurement, but also provides accurate results, which can be applied when a large number of urine samples need to be measured in a short period of time.

Objective:To investigate the expression of iron-regulating erythroid factors in different types of erythropoiesis disorders.Methods:From January 2016 to November 2019, the plasma concentrations of iron-regulating erythroid factors were measured by ELISA methods in 47 patients with different types of erythropoiesis disorders. The adaptation orientation of iron-regulating erythroid factor expression with bone marrow erythropoiesis activities (represented by bone marrow-nucleated erythrocytes ratio) was analyzed.Results:The median plasma growth differentiation factor (GDF) 15 levels in patients with polycythemia vera (PV) , pure red cell aplasia (PRCA) , autoimmune hemolytic anemia (AIHA) , and myelodysplastic syndrome (MDS) were 266.01 ng/L (112.40, 452.37) , 110.63 ng/L (81.41, 220.42) , 52.11 ng/L (32.61, 171.66) , and 276.53 (132.16, 525.70) ng/L, respectively, which were significantly higher than those in normal patients with 37.45 (19.65, 57.72) ng/L (all P < 0.01) . The plasma TWSG1 expression levels were not significantly different in patients with PV, PRCA, AIHA, and MDS from those of normal patients (P>0.05) . The median plasma GDF11 level in PV was 74.75 (10.95, 121.32) ng/L, which was significantly higher than 36.90 (3.38, 98.34) ng/L in normal control subjects ( P<0.01) . However, no statistical differences were observed in the other three subjects ( P>0.05) . The median plasma erythroferrone (ERFE) levels in AIHA and PV were 121.76 ng/L (68.12, 343.11) and 129.63 (47.02, 170.03) ng/L, respectively, with the highest level in AIHA in all the studied types of erythropoiesis disorders. The bone marrow-nucleated erythrocytes ratio was significantly and positively correlated with ERFE ( r=0.458, P=0.001) but not with GDF15 ( r=-0.163, P=0.274) , GDF11 ( r=0.120, P=0.421) , and TWSG1 ( r=-0.166, P=0.269) . Conclusion:The expression profile of iron-regulating erythroid factors is not exactly the same in different types of erythropoiesis disorders. ERFE demonstrated the highest correlation with erythropoiesis activities.

Objective:To study the effect of iron deficiency level for oral iron absorption in iron deficient patients.Methods:37 non-pregnant female patients who were diagnosed with iron deficiency and 13 healthy females who completed their physical examination at the outpatient department of the Anemia Center of the Institute of Hematology & Blood Diseases Hospital from July 2018 to June 2020 were included. Hepcidin and C2-C0 of oral iron absorption test were analyzed in different iron deficiency and serum ferritin level.Results:The median of Hepcidin in IDA, ID/IDE and healthy control group were 4.9 (2.17-32.86) , 26.98 (11.02-49.71) and 69.89 (42.23-138.96) μg/L ( P<0.001) , respectively. Hepcidin level of IDA group was lower than that of ID/IDE group (adjusted P=0.005) and healthy control (adjusted P<0.001) . Hepcidin level of ID/IDE group had no significant difference compared with healthy control (adjusted P=0.22) . The mean of C2-C0 in IDA, ID/IDE and healthy control group were (35.30±21.68) , (37.90±14.06) and (23.57±10.14) μmol/L ( P=0.130) , respectively. Multilinear regression analysis showed C0, SF, sTFR and HGB were independent factors for Hepcidin in iron deficient patients, with an equation of Hepcidin=-31.842-0.642*C0+2.239*SF+1.778*sTFR+0.365*HGB-0.274*RET-HB. We didn't find independent factor of C2-C0. Conclusion:The degree of iron deficiency had an effect on oral iron absorption. Patients of ID/IDE group absorbed iron more slowly than patients of IDA group. Iron deficient patients with normal gastrointestinal function absorbed more iron by oral administration when they were in a more serious iron deficient stage. Hepcidin was a better parameter to distinguish iron absorption level among different iron deficient patients than C2-C0 of oral iron absorption test.

Objective: To compare the difference of the clinical and laboratory characteristics between γδ T-cell large granular lymphocyte leukemia (γδT-LGLL) and αβ T-cell large granular lymphocyte leukemia (αβT-LGLL) . Methods: The clinical and laboratory characteristics of 17 patients with γδT-LGLL and 91 patients with αβT-LGLL in the department of therapeutic center of anemia of enrolled in our hospital from January 2009 to January 2019 were retrospectively analyzed. Results: The median age of the 17 patients with γδT-LGLL was 54 years (range, 25-73 years) , the most common presenting symptom was anemia. In comparison with αβT-LGLL patients, splenomegaly was common (41% and 44%, respectively) , whereas hepatomegaly (12% and 5%, respectively) and lymphadenopathy (6% and 8%, respectively) were rare. The positive rates of antinuclear antibody (59% and 45%, respectively) were high, whereas the positive rates of rheumatoid factor (6% and 10%, respectively) were rare for both groups. There were no differences on peripheral blood counts between the two groups. However, γδT-LGLL patients were found to be predominantly expressed a CD4⁻/CD8⁻ phenotype. Steroid therapy with prednisone was used alone as first-line therapy for 1 patient. Cyclosporin A (CsA) was used alone as first-line therapy for 3 patients. CsA in combination with steroids were administered in 13 patients. After 4 months treatment, 2 patients acquired complete response, 4 patients acquired partial response, the overall response was 35%. Conclusion γδT-LGLL is a rare mature T-lymphocyte proliferative disease. Clinical and laboratory characteristics were quite similar for γδT-LGLL in compare with αβT-LGLL. γδT-LGLL predominantly expressed a CD4⁻/CD8⁻ phenotype. The data presented here indicate the CsA is an effective option for the first-line treatment of γδT-LGLL.

Objective: To evaluate the tolerance and safety of a human-mouse chimeric anti-CD20 monoclonal antibody IBI301 in Chinese patients achieved objective response with CD20⁺ B-cell non-Hodgkin’s lymphoma (NHL). Methods: Nine patients with CD20⁺ B-cell NHL received dose-escalating IBI301 infusions (250 mg/m², n=3; 375 mg/m², n=3; 500 mg/m², n=3, respectively). The data of all patients were collected for safety analyses. The median exposures of 125 mg/m², 375 mg/m², 500 mg/m² dose groups were 243, 690 and 980 mg, respectively. Safety and tolerability were evaluated by monitoring adverse events (AE). The ratios of CD19⁺, CD20⁺ B cells and the levels IgG and IgM were detected to evaluate the pharmacodynamics. Results: Totally 52 events of AE were observed, including 18 events of AE in 125 mg/m² group, 14 events of AE in 375 mg/m² group and 20 events of AE in 500 mg/m² group, respectively. There were 26 adverse reactions of 52 cases of AE, 22 reactions were judged to be probably related to IBI301, and 4 reactions were not probably related to IBI301, all disappeared or returned to baseline levels. Common AE in this study included decreased WBC, upper respiratory infection, decreased neutrophil count, dyspepsia, hyperuricemia, paresthesia, oral mucositis and dizziness. No patients quitted or trial discontinued. No severe AE (SAE) were reported. No dose-limiting toxicity (DLT) events were observed in the study. The ratio of CD20⁺ and CD19⁺ B cells decreased in all subjects. There was no significant changes of the levels of IgG and IgM. Conclusions: The single dose of IBI301 injection was well tolerated, and the AE occurred in the patients recovered. No SAE were reported, No DLT events were observed in the study. The IBI301 caused an elimination of the peripheral CD20-expressing B cells in all patients. Clinical trial registration Chinadrugtrials, CTR20140762.

Objective: To investigate the treatment efficacy of recombinant activated factor Ⅶ (rFⅦa) for bleeding among patients with hematologic disorders. Methods: A total of 38 times of bleeding in 31 patients with hematological disease treated with rFⅦa were analyzed retrospectively. Results: The clinical effective rate of rFⅦa for bleeding management in acquired hemophilia A (AHA) patients/hemophilia patients with inhibitor, acute promyelocytic leukemia (APL) patients and patients with non-APL leukemia was 90% (9/10) , 71.4% (5/7) and 60.0% (3/5) , respectively, which was higher than that in patients following HSCT (30.8%) . The clinical effective rate of rFⅦa for patients with bleeding score of 2 (100.0%) was higher than that with 3 (66.7%) and 4 (54.1%) . The effective rate of rFⅦa was 25.0% (2/5) in 5 patients with cerebral hemorrhage, 66.7% (6/9) in 9 patients with hematuria and 41.7% in 12 patients with gastrointestinal hemorrhage. The curative effect for 3 patients with joints and muscle bleeding and 5 patients with skin, nasal, pharyngeal and gum bleeding was excellent. Following HSCT, among patients with bleeding score of 4 points, high dose and repeated use of rFⅦa did not necessarily achieve a good effect. Among AHA/hemophilia patients with inhibitors and patients with acute leukemia who had bleeding score of 4 points, the use of low dose FⅦa could achieve good therapeutic effect, however the efficacy of lowest dose (22.5 μg/kg) rFⅦa was poor. Conclusions The hemostasis efficacy of rFⅦa is affected by various factors such as diseases, bleeding sites, bleeding score and so on. The use of rFⅦa can achieve good efficacy for bleeding management in AHA patients/hemophilia patients with inhibitor, APL patients and patients with non-APL leukemia. However the efficacy of rFⅦa for bleeding of patients after HSCT is poor. Early use of rFⅦa is important for successful hemostatic treatment. Management of underlying condition is as important as hemostatic treatment.

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.

OBJECTIVETo explore the efficacy and safety of deferasirox in aplastic anemia (AA)patients with iron overload.

METHODSA single arm, multi- center, prospective, open- label study was conducted to evaluate absolute change in serum ferritin (SF)from baseline to 12 months of deferasirox administration, initially at a dose of 20 mg·kg(-1)·d(-1), and the safety in 64 AA patients with iron overload.

RESULTSAll patients started their deferasirox treatment with a daily dose of 20 mg · kg(-1) ·d(-1). The mean actual dose was (18.6±3.60) mg · kg(-1)·d(-1). The median SF decreased from 4 924 (2 718- 6 765)μg/L at baseline (n=64) to 3 036 (1 474- 5 551)μg/L at 12 months (n=23) with the percentage change from baseline as 38%. A median SF decrease of 651 (126-2 125)μg/L was observed at the end of study in 23 patients who completed 12 months' treatment, the median SF level decreased by 1 167(580-4 806)μg/L [5 271(3 420-8 278)μg/L at baseline; 3 036(1 474-5 551)μg/L after 12 months' treatment; the percentage change from baseline as 42% ] after 12 months of deferasirox treatment. The most common adverse events (AEs) were increased serum creatinine levels (40.98%), gastrointestinal discomfort (40.98%), elevated liver transaminase (ALT: 21.31%; AST: 13.11%)and proteinuria (24.59%). The increased serum creatinine levels were reversible and non-progressive. Of 38 patients with concomitant cyclosporine use, 12(31.8%)patients had two consecutive values >ULN, 10(26.3%)patients had two consecutive values >1.33 baseline values, but only 1(2.6%)patient's serum creatinine increased more than 1.33 baseline values and exceeded ULN. For both AST and ALT, no patients experienced two post- baseline values >5 ×ULN or >10 × ULN during the whole study. In AA patients with low baseline PLT count (less than 50 × 10(9)/L), there was no decrease for median PLT level during 12 months' treatment period.

CONCLUSIONSAA patients with iron overload could achieve satisfactory efficacy of iron chelation by deferasirox treatment. The drug was well tolerated with a clinically manageable safety profile and no major adverse events.

Anemia, Aplastic ; drug therapy ; Benzoates ; therapeutic use ; Blood Transfusion ; China ; Ferritins ; blood ; Humans ; Iron ; blood ; Iron Chelating Agents ; therapeutic use ; Iron Overload ; drug therapy ; Liver ; Prospective Studies ; Triazoles ; therapeutic use