Effect of Qinggan Xiefei Fang on increasing susceptibility of influenza virus caused by "liver fire invading lung" / 药学学报

In this study, chronic emotional stress-induced H1N1 influenza susceptibility model was employed to simulate the states of "emotional stagnation" and "liver fire invading lung", and the protective effect of Qinggan Xiefei Fang on viral pneumonia was investigated. Survival rate and morbidity rate of mice were observed within 21 days after H1N1 infection, the symptoms of viral pneumonia and the level of phospholipid peroxidation were detected in lungs of mice after 6-day infection. The experimental results showed that Qinggan Xiefei Fang could alleviate the decline of survival rate and morbidity rate of mice caused by chronic constraint stress loaded with H1N1, inhibit the replication of H1N1 and the production of inflammatory factors, reduce the level of phospholipid peroxidation, and improve the symptoms of pneumonia in mice. The results also showed that compound-target network of Qinggan Xiefei Fang contained 171 compounds and 260 corresponding targets involved in the signaling pathway of oxidative stress, inflammation and immunity. All the above results indicate that Qinggan Xiefei Fang protecting influenza virus pneumonia was related to the regulation of oxidative stress. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Jinan University, in compliance with the Institutional Animal Care Guidelines.

Clinical Effect of Tyrosine Kinase Inhibitors in the Treatment of P230 Chronic Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To observe the curative efficacy of tyrosine kinase inhibitors (TKIs) in the treatment of e19a2 transcript (P230) CML chronic phase (CML-CP) patients.@*METHODS@#The clinical data of 11 P230 CML-CP patients were collected from July 2008 to December 2019. Blood routine examination, bone marrow cytology, chromosome, and BCR-ABL qualitative and quantitative tests were performed at initial diagnosis. After TKIs treatment, BCR-ABL (P230)/ABL in peripheral blood was regularly detected to evaluate molecular response by real-time quantitative PCR.@*RESULTS@#There were 11 patients (7 males and 4 females) in chronic phase from 6 domestic hospitals enrolled, their median age was 46 years old (range from 19 to 56 years old). Among 4 patients treated with imatinib (400 mg, qd) firstly, 3 cases switched to nilotinib (400 mg, bid) and 1 case switched to dasatinib (100 mg, qd) due to failure to achieve best molecular response at the landmark time or mutation of ABL kinase. Then major molecular response (MMR) was obtained within 1 year. In addition, 5 patients were treated with nilotinib (300 mg, bid) and 2 patients with dasatinib (100 mg, qd) as first-line treatment, all of them got MMR within 6 months.@*CONCLUSION@#For intolerance or resistance to imatinib, second-generation TKIs can enable P230 CML patients to achieve deeper molecular response, and MMR in a short time.

The Establishment and Identification of Acute Myeloid Leukemia NOD-SCID-IL2rg / 中国实验血液学杂志

OBJECTIVE@#To establish the in vivo traceable acute myeloid leukemia mice model with Luciferase-Expressing KG1a Cells.@*METHODS@#KG1a cells with stable luciferase gene expression (called as KG1a-Luc cells) were constructed by lentivirus transfection, then sifted out by puromycin. Eighteen male NOD-SCID-IL2rg@*RESULTS@#KG1a cells expressing luciferase stably were successfully obtained. The tumor luminescence wildly spread at day 17 captured by in vivo imaging. The KG1a-Luc tumor cells could be detected in the peripheral blood of the mice, with the average percentage of (16.27±6.66)%. The morphology and pathology result showed that KG1a-Luc cells infiltrate was detected in bone marrow, spleens and livers. The survival time of the KG1a-Luc mice was notably shorter as compared with those in the control group, the median survival time was 30.5 days (95%CI: 0.008-0.260).@*CONCLUSION@#The acute myeloid leukemia NOD-SCID-IL2rg

Expression and Significance of BTLA and Its Ligand HVEM in Patients with Chronic Myelomonocytic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression and significance of B and T lymphocyte weakening factor (BTLA) in patients with chronic myelomonocytic leukemia (CMML).@*METHODS@#Real-time PCR was used to detect the expression of BTLA and its ligand HVEM mRNA in 11 patients with chronic myelomonocytic leukemia and 11 normal donors. Flow cytometry was used to detect expression of BTLA and its HVEM on the cell surface of peripheral blood T lymphocytes and γδ T cells.@*RESULTS@#The median values of BTLA and its ligand HVEM mRNA expression in peripheral blood of patients with CMML were 0.009% and 559.4%, respectively, which were significantly lower than those of normal controls (0.053% and 1031%)(P<0.001). The expression level of BTLA and HVEM on cell surface of peripheral lymphocytes was not significantly different from that in normal controls (P=0.3031 and 0.2576), however, the proportion of peripheral blood T lymphocytes in patients with CMML (median: 37.73%) was significantly lower than that in controls (median 69.23%)(P=0.0005). The expression of BTLA on the surface of γδ T cells in peripheral blood of patients with CMML (median: 23.26%) was significantly lower than that of the controls (median: 52.64%) (P<0.05), and there was no significant abnormality in HVEM expression (P=0.2791).@*CONCLUSION@#The expression of BTLA and its ligand HVEM, the proportion of T lymphocytes and the expression of BTLA on the surface of γδ T cells in patients with CMML are reduced. The effects of these abnormalities on T cell function and prognosis and efficacy of patients need to be further observed.

Regulatory Effect of Exosomes Derived from Human Umbiilcal Cord Mesenchymal Stem Cells on Treg and TH17 Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of exosomes from human umbilical cord mesenchymal stem cells on the development of Treg and TH17 cells.@*METHODS@#Exosomes from the serum-free-culture supernatants of hUC-MSC were harvested by ultracentrifugation. The electron microscopy, nanoparticle tracking analysis and western blot were used to identify the hUC-MSC-exosomes, such as the morphology, the paticle chameter, and the protein content. The PBMC stimulated with anti-CD3/CD28 were incubated with the exosomes for five days, and then the percentage changes of Treg and TH17 cells were analyzed by using flow cytometry.@*RESULTS@#The hUC MSC-derived exosomes were saucer-like in morphology the averge diameter was approximately 142 nm. They were identified as positive for CD9 and CD63. Flow cytometry showed that the proportion of CD4CD25Foxp3 Treg cells in the PBMC were significantly higher, but the proportion of CD4IL17A T cells in the hUC-MSC-exosome group was obviously lower than that in the group without the hUC-MSC-exosom (control group) (P<0.05).@*CONCLUSION@#The hUC-MSC-exosomes have an immunomodulatory effect on T cells in vitro by increasing the ratio of Treg and reducing the ratio of TH17 cells, expecting the hUC-MSC-exosom as a novel cell-free target for immunotherapy.

Association between plasma homocysteine level and renal function / 中国实用内科杂志

OBJECTIVE: To investigate the association between homocysteine and renal function as well as possible influencing factors in inpatient population. METHODS: From January 2014 to December 2015, a total of 27,025 hospitalized people who were admitted to the First Hospital of Peking University and were tested for plasma homocysteine were enrolled. Multiple linear regression model was performed to determine the relationship between homocysteine and eGFR. RESULTS: After excluding patients with cardiovascular disease and patients taking antihypertensive drugs, 6681 inpatient participants were included for analysis. After adjusting for age, blood pressure and other related factors, we found that eGFR decreased significantly(β=-0.53, SE=0.02, P<0.001) with the increase of homocysteine. Furthermore, the gender, age and renal functional state, had significant influence the relationship between homocysteine and eGFR. In women, those younger than 60 years old and renal impairment(eGFR<90 mL/[min·1.73 m~2]) population, the correlation was more significant. CONCLUSION: The association between homocysteine and eGFR is significant in inpatient population.

Changes of WT1 mRNA expression level in patients with myelodysplastic syndromes after hypomethylating agents and its prognostic significance / 中华血液学杂志

Objective: To monitor the WT1 mRNA level and its dynamic changes in patients with myelodysplastic syndromes (MDS) after hypomethylating agents (HMA) , as well as to assess the significance of WT1 mRNA levels and its dynamic changes in evaluating the efficacy of HMA and distinguishing the disease status of heterogeneous patients with stable disease (SD) . Methods: Bone marrow or peripheral blood samples of 56 patients with MDS who underwent hypomethylating agents (≥4 cycles) from November 2009 to March 2018 were tested by real-time quantitative polymerase chain reaction (PCR) to detect the expression of WT1 mRNA, and to observe the correlation between the dynamic changes of WT1 mRNA expression and clinical efficacy and prognosis of patients. Results: WT1 mRNA expression levels of MDS patients decreased significantly after 3 cycles of hypomethylating agent treatment. Besides, the WT1 mRNA expression levels of patients increased significantly after diseases progression. According to the dynamic changes of WT1 mRNA expression levels during SD, 45 cases could be further divided into increased group and non-increased group. In those SD patients with increased WT1 mRNA expression level, the ratio of suffering disease progression or transformation to AML was 95.65% (22/23) , whereas the ratio turned to be 9.09% (2/22) for the non-increased group (χ(2)=33.852, P<0.001) . Compared with those SD patients reporting no increase in WT1 mRNA expression level, the overall survival[17 (95%CI 11-23) months vs not reached, P<0.001] and progression-free survival [13 (95%CI 8-18) months vs not reached, P<0.001] of those SD patients reporting increase in WT1 mRNA expression level were significantly shorter. Conclusion: WT1 mRNA expression level is a useful indicator to assess the efficacy of hypomethylating agents in MDS patients. Especially in patients with SD, detection of the changes in WT1 mRNA expression level is able to predict disease progression and help to make clinical decision.

Artesunate attenuate chronic graft-versus-host disease by regulating Th17/Treg balance / 中华血液学杂志

Objective: To investigate the effects of artesunate treatment on chronic graft-versus-host disease (cGVHD). Methods: Recipient BALB/c mice received 8 × 10(6) bone marrow cells with 8×10(6) spleen cells from B10D2 mice. Artesunate solubilized in acetone was injected intraperitoneally every day at the dose of 1 mg/kg at Day 28 after BMT. The clinical scores, survival and histopathological damage were analyzed. The frequency of Th17 and Tregs in PB and spleens from the mice were evaluated by flow cytometry. In addition, CD4(+) T cells from the spleens of mice were cultured in vitro, then stimulated with artesunate, the frequency of Th17 and Tregs in these splenocytes were evaluated by flow cytometry. Results: Artesunate administration diminished clinical and histopathological damage, and improved the survival of cGVHD mice[(46.57±7.83)% vs (55.71±6.99)%, χ(2)=5.457, P=0.020]; Artesunate contributed to Tregs development [(4.45±0.04)% vs (8.40±0.23)%, t=15.679, P<0.001; (6.62±0.24)% vs (10.48±0.48)%, t=6.587, P=0.003] while decreased Th17 cells [(1.51±0.18)% vs (0.58±0.19)%, t=7.233, P<0.001; (1.48±0.38)% vs (0.71±0.18)%, t=3.653, P=0.011] expressions in both PB and spleens, and decreased the Th17/Treg ratio (0.34±0.05 vs 0.09±0.03, t=7.621, P=0.002; 0.19±0.03 vs 0.06±0.02, t=6.993, P=0.002). Moreover, artesunate suppressed the Th17 cells expressions [(0.82±0.37) % vs (3.39±1.22) %, t=4.044, P=0.007] and contributed to Tregs development [(34.63±1.29) % vs (14.28±1.69) %, t=19.119, P<0.001], and also decreased the Th17/Treg ratio (0.24±0.09 vs 0.02±0.01, t=4.780, P=0.003) in vitro. Conclusions: Artesunate suppressed the Th17 cells expressions and contributed to Tregs development, which provided new sights into the development of a novel drug for cGVHD, e.g., artemisinin.

Study of RET proto-oncogene mutations in two pedigrees affected with multiple endocrine neoplasia type 2A / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the pattern of RET proto-oncogene mutations in two pedigrees affected with multiple endocrine neoplasia type 2A (MEN2A).</p><p><b>METHODS</b>Peripheral blood samples were collected from members of the two pedigrees, with total genomic DNA extracted for polymerase chain reaction (PCR). PCR products of 7 exons of the RET proto-oncogene (including exons 8, 10, 11, 13, 14, 15, 16) which have higher mutation rates were purified and subjected to direct sequencing. Suspected mutations in the 2 probands were verified in other members of the pedigrees. To exclude other mutations, PCR products of remaining 14 exons were sequenced in the proband from pedigree 1.</p><p><b>RESULTS</b>A novel heterozygous mutation, 1893-1895delCGA, was detected in exon 11 of the RET proto-oncogene among 3 patients and 2 unaffected members from pedigree 1, while a heterozygous mutation, Cys634Arg, was detected in exon 11 among 2 patients and 1 unaffected family member from pedigree 2.</p><p><b>CONCLUSION</b>The heterozygous 1893-1895delCGA and Cys634Arg mutations of the RET proto-oncogene probably underlie the disease in the two pedigrees. Above discovery has enriched the human gene mutation database.</p>

A comparison of clinical characteristics between 2 pedigrees of multiple endocrine neoplasia type 2A with different RET mutations / 中华内科杂志

Multiple endocrine neoplasia type 2A (MEN2A) is a hereditary syndrome. Here, two different RET proto-oncogen mutation were identified from family members of two MEN2A pedigrees by genetic screening. One RET mutations were found at codons 1893 and 1895 in exon 11 (1893-1895delCGA) from pedigree 1, which is a novel mutation, the other occurs at codon 634 (Cys634Arg) in exon 11 from pedigree 2. However, the clinical characteristics were similar in the patients of the two pedigrees. All the patients were in middle-age at onset. Most of them were firstly diagnosed with bilateral adrenal pheochromocytoma with different degrees of thyroid abnormalities (elevated serum calcitonin with or without thyroid mass, or had been diagnosed with medullary thyroid carcinoma). Some family members were with elevated serum parathyroid hormone but with no other evidences for hyperparathyroidism.

Genetic diversity of cytochrome C oxidase subunit Ⅰ genes in Aedes albopictus from dengue surveillance sites in Fujian Province, China / 中国人兽共患病学报

The mosquito Aedes albopictus is the primary vector for dengue virus transmission in Fujian Province.Despite that active dengue surveillance has been launched in several sites since 2005,the genetic diversity of A.albopictus from these sites remains exclusive.In this study,mosquito pools collected from dengue surveillance sites during 2015-2016 were randomly selected,the full-length mitochondrial cytochrome C oxidase subunit Ⅰ (mtDNA-COⅠ) were amplified and sequenced.Preliminary sequence alignment of 12 amplicons with the reference sequence indicated 99 ％ homology at nucleotide level,due to varia tions at 9 nucleotide sites.Three haplotypes,namely H02,H03 and H08,were determined based on phylogenetic analysis with 72 reference sequences of known haplotypes.These observations facilitate surveillance and control of arboviral diseases in Fujian.

Viral gastroenteritis outbreaks associated with new recombinant strain GⅡ.P16/GⅡ.2 of norovirus in Fujian, 2016 / 中国人兽共患病学报

We delineated the molecular characteristic of recombinant strain GⅡ.P16/GⅡ.2 of norovirus associated with acute viral gastroenteritis outbreaks in Fujian Province in winter of 2016.Norovirus were detected in specimens of patients collected from the gastroenteritis outbreaks by real time reverse transcription-PCR and reverse transcription-PCR (RT-PCR).The PCR products of the positive samples were purified,and partial RNA dependent RNA polymerase (RdRp) gene and partial capsid gene were sequenced.The sequences were analyzed using bioinformatics software and online database,and phylogenetic tree were also constructed.Norovirus were detected in all 18 stools.Analysis of 9 positive sequences indicated an emergence of norovirus GⅡ.P16/ GⅡ.2 and confirmed being the cause of gastroenteritis outbreaks.All the strains shared homology of 98％ with strains of Kawasaki 194 of Japan detected in 2016 and 97.7％-98.8％ with IPH2161-08VG06 of Belgium detected in 2008,RdRp and capsid separately.These outbreak strains showed some degree of differences from the predominant strain,2012 Sydney GⅡ.4 variant.This is the first time to have found norovirus GⅡ.P16/ GⅡ.2 causing viral gastroenteritis outbreaks in Fujian.More in-depth analysis of the Norovirus GⅡ.P16/ GⅡ.2 could be useful to optimize preventative strategies and develop new and more effective therapeutic measure.

Molecular epidemiology of HFMD-associated pathogen coxsackievirus A4 in Fujian Province, 2011-2014 / 中国人兽共患病学报

To analyze the epidemiology,genetic variation and genetic evolution of coxsackievirus A4 (CVA4) in patients with hand,foot and mouth disease in Fujian,the virus isolates were molecular typed and amplified the whole VP1 region by RT-PCR,then the genetic variation and evolution were studied.The results showed that 33 CVA4 cases (8.1％) were confirmed from the 407 non-EV71 non-CVA16 HFMD cases in Fujian Province during 2011 and 2014,accounting for 31 cases in 2012 and 2 cases in 2014.Compared with common characteristics of the HFMD epidemic,no specificity in the distribution of CVA4 cases was found between gender and age groups.Sequence analysis of VP1 nucleotide sequences of Fujian CVA4 isolates showed that the nucleotide and amino acid sequences similarity were 92.6 ％-100 ％ and 95.7 ％-100 ％ respectively,low similarity with the prototype (83.7％-85.4％,96.1％-99.0％) and abroad isolates (82.1％-89.1％,90.4％-99.6％) both in nucleotide and amino acid sequences,high similarity with domestic isolates both in nucleotide and amino acid sequences,with the similarity of 87.9％ 99.2 ％ and 96.1％-100 ％.The results from phylogenetic tree showed that the genetic distance between Fujian CVA4 isolates and the prototype and abroad strains was far,and the genetic distance was close to domestic isolates in China.The distribution of the phylogenetic trees of Fujian CVA4 strains showed multiple branches.Therefore,CVA4 is the major HFMD associated-pathogen other than EV71,CVA 16,CVA6,and CVA10 in Fujian Province from 2011 to 2014.CVA4 strains from Fujian Province is co-circulating and co-evolving with other domestic isolates.There is existence of multiple closely related CVA4 transmission chains in various regions of Fujian.

Viral gastroenteritis outbreaks associated with new recombinant strain GⅡ.P16/GⅡ.2 of norovirus in Fujian, 2016 / 中国人兽共患病学报

We delineated the molecular characteristic of recombinant strain GⅡ.P16/GⅡ.2 of norovirus associated with acute viral gastroenteritis outbreaks in Fujian Province in winter of 2016.Norovirus were detected in specimens of patients collected from the gastroenteritis outbreaks by real time reverse transcription-PCR and reverse transcription-PCR (RT-PCR).The PCR products of the positive samples were purified,and partial RNA dependent RNA polymerase (RdRp) gene and partial capsid gene were sequenced.The sequences were analyzed using bioinformatics software and online database,and phylogenetic tree were also constructed.Norovirus were detected in all 18 stools.Analysis of 9 positive sequences indicated an emergence of norovirus GⅡ.P16/ GⅡ.2 and confirmed being the cause of gastroenteritis outbreaks.All the strains shared homology of 98％ with strains of Kawasaki 194 of Japan detected in 2016 and 97.7％-98.8％ with IPH2161-08VG06 of Belgium detected in 2008,RdRp and capsid separately.These outbreak strains showed some degree of differences from the predominant strain,2012 Sydney GⅡ.4 variant.This is the first time to have found norovirus GⅡ.P16/ GⅡ.2 causing viral gastroenteritis outbreaks in Fujian.More in-depth analysis of the Norovirus GⅡ.P16/ GⅡ.2 could be useful to optimize preventative strategies and develop new and more effective therapeutic measure.

Molecular epidemiology of HFMD-associated pathogen coxsackievirus A4 in Fujian Province, 2011-2014 / 中国人兽共患病学报

To analyze the epidemiology,genetic variation and genetic evolution of coxsackievirus A4 (CVA4) in patients with hand,foot and mouth disease in Fujian,the virus isolates were molecular typed and amplified the whole VP1 region by RT-PCR,then the genetic variation and evolution were studied.The results showed that 33 CVA4 cases (8.1％) were confirmed from the 407 non-EV71 non-CVA16 HFMD cases in Fujian Province during 2011 and 2014,accounting for 31 cases in 2012 and 2 cases in 2014.Compared with common characteristics of the HFMD epidemic,no specificity in the distribution of CVA4 cases was found between gender and age groups.Sequence analysis of VP1 nucleotide sequences of Fujian CVA4 isolates showed that the nucleotide and amino acid sequences similarity were 92.6 ％-100 ％ and 95.7 ％-100 ％ respectively,low similarity with the prototype (83.7％-85.4％,96.1％-99.0％) and abroad isolates (82.1％-89.1％,90.4％-99.6％) both in nucleotide and amino acid sequences,high similarity with domestic isolates both in nucleotide and amino acid sequences,with the similarity of 87.9％ 99.2 ％ and 96.1％-100 ％.The results from phylogenetic tree showed that the genetic distance between Fujian CVA4 isolates and the prototype and abroad strains was far,and the genetic distance was close to domestic isolates in China.The distribution of the phylogenetic trees of Fujian CVA4 strains showed multiple branches.Therefore,CVA4 is the major HFMD associated-pathogen other than EV71,CVA 16,CVA6,and CVA10 in Fujian Province from 2011 to 2014.CVA4 strains from Fujian Province is co-circulating and co-evolving with other domestic isolates.There is existence of multiple closely related CVA4 transmission chains in various regions of Fujian.

Effectiveness of CLAT Protocol for Treating Patients with Refractory Acute Myeloid Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the clinical efficacy and toxicity of CLAT protocol (cladribine, cytarabine and topotecan) for treating patients with refractory acute myeloid leukemia (R-AML).</p><p><b>METHODS</b>A total of 18 patients with R-AML (median age 37 years, range 18 to 58 years; male n = 16, female n = 2) were treated with CLAT protocol, which consisted of cladribine 5 mg/m(2)/d, i.v. on days 1-5, cytarabine 1.5 g/m(2)/d, i.v. on days 1-5, topotecan 1.25 mg/m(2)/d, i.v. on days 1-5 and G-CSF 300 µg/d subcutaneous injection on day 6 until neutrophile granulocyte recovery.</p><p><b>RESULTS</b>Out of 18 patients 2 died of severe infection before the assessment. Among 16 evaluated patients, 10 (55.6%) achieved complete remission (CR), and 2 (11.1%) achieved partial remission (PR), the overall response rate was 66.7%, the rest 4 patients did not respond (NR). The median overall survival time and DFS for the CR patients was 9.5 months (95%CI: 6.7-16.64) and 9.5 months (95%CI: 6.1-16.7) respectively. The 1 year OS and DFS rates were 45% and 46.9%, respectively. All patients developed grade 4 of granulocytopenia and thrombocytopenia, the median duration was 13 (range 2 to 21) days and 12 days (range 2 to 21), respectively, all patients developed infection, 2 patients died of severe infection. The most common non-hematological side effects included nausea, vomiting, diarrhoea, rash, aminotransferase or bilirubin elevation and were grade 1 to 2.</p><p><b>CONCLUSION</b>The CLAT protocol seems to have promising for the treatment of refractory AML patients, and patients well tolerated. This CLAT protocol offers an alternative treatment for R-AML patients who received severe intensive treatment, especially with anthracycline-containing chemotherapy.</p>

C-kit mutation in acute myeloid leukemia patients with AML1-ETO fusion gene and its clinical significance / 中国实验血液学杂志

This study was aimed to investigate the c-kit mutation in acute myeloid leukemia (AML) patients with AML1-ETO and analyze its relation with clinical and laboratorial features and prognosis. PCR and sequencing methods were used to detect the c-kit 17 exon mutations in 31 AML patients with AML1-ETO. The relation of the c-kit mutation with clinical features, results of laboratorial examination and prognosis of disease were analyzed. The results showed that the c-kit mutation was found in 14 out of 31 AML patients and the mutation frequency was 45.16%. Male patients had a higher incidence of c-kit mutation than that of female patients (P = 0.020). The proportion of patients with newly diagnosed white blood cell>10×10(9)/L and with extramedullary infiltration in mutated group were higher than those in unmutated group respectively. No significant difference was observed at the age (P = 0.437) and the rate of bone marrow blasts(P = 0.510) between the above mentioned two groups. The difference in complete remission rate (64.29% vs 80%, P = 0.344)and relapse rate (58.33% vs 21.43%, P = 0.054) between c-kit mutated and c-kit unmutated groups were not significant. While the c-kit mutated group had a significant higher death rate as compared with c-kit unmutated group (57.14% vs 20%, P = 0.039). It is concluded that the c-kit mutation is frequent in AML patients with AML1-ETO and the c-kit mutated patients have a poor prognosis. It is important to detect c-kit mutation in routine clinical practice for patient's risk stratification, evaluation of prognosis and selection of effective treatment.

Predictive value of molecular response after treatment with tyrosine kinase inhibitor for 3 months in patients with chronic myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To understand the predictive value of early monitoring BCR-ABL transcripts in patients with chronic myeloid leukemia (CML) after treatment with tyrosine kinase inhibitor (TKI), and to provides the information for early assessment of prognosis and treatment options.</p><p><b>METHODS</b>BCR-ABL transcripts of 53 CML patients before and after TKI treatment were detected by using real-time quantitative RT-PCR. The relationship between BCR-ABL transcripts level after TKI treatment for 3 months and the later molecular response, progression and mutation was analyzed.</p><p><b>RESULTS</b>The median values of BCR-ABL transcripts in peripheral blood samples from 30 newly diagnosed patients were 43.99%, which was used as a baseline of BCR-ABL transcripts for molecular response evaluation. Of 53 patients, 31 (58.49%) had a BCR-ABL mRNA ≤ 4.40% (reduced more than 1 log) and 22 (41.51%) greater than 4.40% (reduced to less than 1 log) after 3 months of TKI treatment. The former 31 patients had a significantly higher 18-months cumulative incidence of major molecular response (MMR) (90.32% vs 18.18%, P=0.000) and 3-year cumulative incidence of complete molecular response (CMR) (48.39% vs 0, P=0.000) compared with the latter 22 patients. The lower BCR-ABL level was, the earlier MMR reached. The proportion of patients with a mutation in group of BCR-ABL mRNA>4.40% was significantly higher than that of BCR-ABL mRNA ≤ 4.40% (22.73% vs 0, P=0.021). The incidence of progression increased in group of BCR-ABL mRNA>4.40%, but the difference was not statistically significant (P=0.052).</p><p><b>CONCLUSION</b>It is important for the prognosis evaluation of the patients to monitor the level of BCR-ABL transcripts at 3 months after TKI treatment, which might help to early optimization of treatment and to improve curative effect of CML patients.</p>

A retrospective study of kidney insufficiency in adult patients after myeloablative allogeneic hematopoietic stem cell transplantation / 中国实验血液学杂志

The aim of this study was to investigate the renal function in 149 patients receiving myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) from June 2005 to June 2010 in our hospital, and analyze the risk factors resulting in kidney insufficiency and experience in diagnose and therapy. The creatinine clearance (CrCL) and serial creatinine level were evaluated before and after allo-HSCT within 100 days and 1 year. Non-radiation conditioning regimens were used for any patients. The acute kidney insufficiency (AKI) was defined as at least a 1.5-fold rise in serum creatinine level after allo-HSCT within the first 100 days. The chronic kidney insufficiency (CKI) was defined as the creatinine clearance < basal level within 3 months to 1 year after allo-HSCT. The results showed that the kidney insufficiency was found in 41 patients, in which the incidence of AKI was 32/149 (21.5%). CsA, amphotericin B (P = 0.025) and ES (P = 0.022) were defined as risk factors for AKI. The incidence of CKI was 18/138 (13%). cGVHD (P = 0.013) and TA-TMA (P = 0.012) were associated with the development of CKI. The 2-year survival was lower in patients with kidney dysfunction than that in patients without kidney dysfunction (39% vs 74.1%, P < 0.001). The main factors resulting in kidney insufficiency were defined as infection (52%), GVHD (20%), TA-TMA (12%) and tumor relapse (12%). It is concluded that kidney insufficiency is an important complication of allo-HSCT. Careful monitoring kidney function, minimizing the use of amphotericin B, prophylaxis and effective treatment of fungal infection, GVHD and TA-TMA may be effective preventive measures to decrease the incidence of kidney insufficiency.

Clinical study of intravenous injecting itraconazole as empirical antifungal therapy for patients with hematological malignancies / 中国实验血液学杂志

This study was purposed to investigate the efficacy and safety of intravenous injecting itraconazole (ITCZ) as empirical antifungal therapy in the patients with hematological malignancies. According to recommendation in IDSA guidebook, the patients suffered from fever during neutropenia and inefficacy of treatment using broad-spectrum antibiotics for 4 days should receive intravenous injection of ITCZ as empirical antifungal therapy. The results showed that the overall clinical response rate to ITCZ injection was 62.9% (22/35), and the success rate of achieving composite endpoints was 54.3% (19/35). Mild adverse reactions were observed in 6 patients (17.1%). The injection of ITCZ was stopped in 2 patents (5.7%) due to adverse reaction. Further analysis revealed that the response rate was higher in patients with fever prior to the start of ITCZ within five days than beyond five days (P = 0.031). The response rate was higher in patients with possible invasive fungus infection (IFI) than that in patients with probable and confirmed IFI (P = 0.002). The prophylactic antifungal treatment during neutropenia displayed no significant influence on efficacy of empirical antifungal therapy with itraconazole (P = 0.054). It is concluded that the good efficacy and safety of empirical ITCZ injection for hematological malignancies patients is efficient and safe.