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Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.
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Objective:To evaluate risk factors and available treatments of extramedullary relapse (EMR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myeloid leukemia.Methods:A total of 280 patients were retrospectively analyzed from January 2008 to December 2018 in Affiliated Cancer Hospital of Zhengzhou University. Clinical data were collected including disease patterns, pre-transplantation status, chromosome karyotype, conditioning regimen, types of donor, extramedullary disease before transplantation and graft-versus-host disease (GVHD). The log-rank test and Cox proportional hazard model were uesd for univariate analysis and multivariate analysis, respectively.Results:Twenty patients developed EMR (7.14%). The median time of EMR was 7.5 (1-123) months after allo-HSCT. The mortality of EMR was 80% (16/20). Univariate analysis identified disease patterns, second complete remission (CR2) or progressive disease before transplantation, extramedullary disease, abnormal karyotype and conditioning regimen without total body radiation as significant factors correlated to EMR ( P<0.05). Multi-variable analysis revealed that CR2 or progressive disease ( RR=3.468,95% CI 2.189-7.786), abnormal karyotype ( RR=1.494,95% CI 1.020-2.189) and extramedullary disease before transplantation ( RR=8.627,95% CI 3.921-18.452) were independent risk factors of EMR. Conclusions:The clinical outcome of EMR after allo-HSCT is poor.It is crucial to comprehensively assess and identify EMR as early as possible.
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Objective@#To identify the initial chest computed tomography (CT) findings and clinical characteristics associated with the course of coronavirus disease 2019 (COVID-19) pneumonia. @*Materials and Methods@#Baseline CT scans and clinical and laboratory data of 72 patients admitted with COVID-19 pneumonia (39 men, 46.2 ± 15.9 years) were retrospectively analyzed. Baseline CT findings including lobar distribution, presence of ground glass opacities, consolidation, linear opacities, and lung severity score were evaluated. The outcome event was recovery with hospital discharge. The time from symptom onset to discharge or the end of follow-up (for those remained hospitalized) was recorded. Data were censored in events such as death or discharge without recovery. Multivariable Cox proportional hazard regression was used to explore the association between initial CT, clinical or laboratory findings, and discharge with recovery, whereby hazard ratio (HR) values 4 vs. ≤ 4 [reference]: adjusted HR = 0.41 [95% confidence interval, CI = 0.18–0.92], p = 0.031) and initial lymphocyte count (reduced vs. normal or elevated [reference]: adjusted HR = 0.14 [95% CI = 0.03–0.60], p = 0.008) were two significant independent factors that influenced recovery and discharge. @*Conclusion@#Lung severity score > 4 and reduced lymphocyte count at initial evaluation were independently associated with a significantly lower rate of recovery and discharge and extended hospitalization in patients admitted for COVID-19 pneumonia.
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Objective@#To investigate the characteristics and prognosis of clonal chromosomal abnormalities appearing in Philadelphia negative metaphases (CCA/Ph-) cells in chronic myeloid leukemia (CML) with tyrosine kinase inhibitor (TKI) therapy.@*Methods@#The clinical data of 30 cases with CCA/Ph- during TKI treatment in Henan Cancer Hospital from August 2007 to July 2017 were retrospectively analyzed. The univariate factor was analyzed by Kaplan-Meier method. Multiple-factor was analyzed by Cox proportional risk model.@*Results@#Of the 30 cases, 19 (63.3%) were males. At the first detection of CCA/Ph- the median age was 44 (rang 14-68) years old and the median treatment of TKI was 13 (rang 2-94) months. The clones proportion of first detected CCA/Ph-≥ 50% was found in 18 (60.0%) cases. TKI treatment for 3 months with BCR-ABLIS less than 10% was seen in 14 (46.7%) patients. 63.3% (19/30) of CCA/Ph- was transient (only one time) and 36.7% (11/30) was repeated (≥2 times) . Trisomy 8 dominant accounted for 60.0% (18/30) , -7/7q- for 13.3% (4/30) , loss of chromosome Y 6.7%. With a median of follow-up 50 months, 76.7% (23/30) cases were in complete cytogenetic response (CCyR) ; 63.3% (19/30) in major molecular response (MMR) , 43.3% (13/30) in undetectable minimal residual disease (UMRD) . The median event-free survival rate of (EFS) were 44 months, and 2-year and 5-year EFS were (82.1±7.3) % and (52.4±12.8) %, respectively. The median overall survival (OS) were 50 months, and 2-year and 5-year OS rates were (92.6±5.0) % and (77.2±14.7) %, respectively. Univariate analysis shows that the 2-year EFS of who in males, more than 2 times CCA/Ph-, BCR-ABLIS>10% at 3 months after TKI were significantly lower than women, transient CCA/Ph-, and BCR-ABLIS≤10% (P<0.05) . The 2-year OS rate in whom the occurrence frequency of CCA/Ph- more than twice was significantly lower than those with transient CCA/Ph- (P<0.05) . Multivariate analysis showed that CCA/Ph- was an independent risk factor (RR=4.741, 95%CI 1.21-18.571, P=0.018) for EFS in CML patients.@*Conclusion@#Trisomy 8, -7/7q-, and -Y were the most common CCA/Ph- during TKI treatment, with high clones proportion of ≥50%. CCA/Ph- mainly occurred transiently or was permanent occasionally. CCA/Ph- recurrence (≥2 times) was an independent risk factor for EFS and OS in CML with TKI.
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Objective@#To investigate the influence of additional clonal chromosome abnormalities in Ph negative cells (CCA/Ph-) on the efficacy of chronic myeloid leukemia (CML) after tyrosine kinase inhibitors (TKI) treatment.@*Methods@#The clinical data of 28 CML patients with CCA/Ph- treated in Henan Cancer Hospital from July 2014 to December 2017 were analyzed retrospectively. The univariate analysis was carried out by Kaplan-Meier method. Multivariate analysis was done by Cox proportional risk model.@*Results@#A total of 28 CCA/Ph-patients were recruited including 17 males and 11 females with median age of 42.5 years old. The most common CCA/Ph-were trisomy 8 (60.7%), monosomy 7 (14.3%). 64.3% CCA/Ph-were transient and 35.7% recurrent (more than 2 times). Cytopenia in two or three lineages of peripheral blood was seen in 42.9% patients. As to the efficacy, 89.3% patients achieved major cytogenetic response (MCyR), 25% with major molecular response (MMR). The median follow-up time was 26.5 months. Treatment failure (TF) of TKI occurred in 32.1% patients with median duration of response 8 (1-41) months. Univariate analysis showed that TF rate was significantly correlated with the frequency of CCA/Ph-and cytopenia (all P<0.05). The MMR rate was also significantly correlated with cytopenia (P<0.05). Cytopenia of two lineages or pancytopenia was an independent risk factor related to MMR rate (RR=3.868, 95%CI 1.216-12.298, P=0.022) .@*Conclusions@#Cytopenia in CCA/Ph-appears to be an independent risk factor of MMR in CML patients with TKI treatment. The recurrent CCA/Ph-may link to higher treatment failure rate. Drug withdrawal or alternative strategy should be considered according to response and the ABL kinase mutations.
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Objective@#To observe the pregnancy outcome among patients with chronic myeloid leukemia (CML) treated with Nilotinib (NIL) .@*Methods@#Clinical data of pregnancy delivery in CML patients treated with NIL from March 2015 to January 2019 were retrospectively collected.@*Results@#A total of 11 patients were recruited with median pregnancy age 28 (25-40) years. The median duration of NIL treatment before pregnancy was 34 (3-48) months. There were 12 pregnancies, included 2 planned ones and 10 (83.3%) unplanned. In the 10 unplanned patients, 9 (90.0%) received NIL 600 mg/d. The median exposure time were 4 (4-7) weeks. In eight patients with delivery outcomes, 5 cases had well-developed babies, 2 had spontaneous abortion and 1 case with an baby of syndactyly deformity, whose mother was exposed to NIL 600 mg/d for 7 weeks in the early trimester of pregnancy. Seven infants were 4 boys and 3 girls with the median height at birth 50 (41-54) cm and median weight 3.2 (3.0-4.6) kg. They all grew with a normal pattern and well developed. Now the median age is 19 (4-41) months. The disease status during 12 pregnancies included 3 cases in CMR, 2 cases in MR4.0, 3 cases in MMR, 4 cases not acquiring MMR. The median time of drug discontinuation was 35 (15-36) weeks during pregnancy. No patient lost CHR during this period.@*Conclusions@#Female CML patients exposed to NIL 600 mg/d for 4 weeks in early pregnancy can give birth to normal babies, but there is still a risk of spontaneous abortion and congenital malformations.
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Objective To survey the current status and training requirement of rural doctors in Hebei province.Methods A questionnaire survey was conducted among1 200 rural doctors selected from 11 cities of Hebei province by stratified sampling from October to December 2017.The self-designed questionnaire included general condition,job satisfaction,impact of medical reform policies,training needs of rural doctors.Results A total of 1 200 questionnaires were distributed and 1 170 valid ones were retrieved with a recovery rate of 97.5％.Among the 1 170 responders,there were 726 males(62.1％) and 444 females (37.9％);748 (63.9％) were aged more than 40 years;612 (52.3％) hold secondary school degree;826 (70.6％) had been working in the village for more than 10 years,and the overall job satisfaction rate was 30.8％ (360/1 170).Among all responders,73.8％ (864/1 170) worked in the standardized village clinics,and 72.0％ (842/1 170) were contracted with local residents as family doctors;52.8％ (618/1 170) responders believed that the reform policy improved the health care for villagers.In all responders,98％ (1 147/1 170)thought they needed training,93.6％ (1 095/1 170) had received training.The training contents they most needed werethe management of common diseases (904,77.3％),followed by medical humanities(650,55.6％)and first aid knowledge (492,42.1％).The influencing factors for training were lack of time,no energy (656,54.3％),lack of appropriate training forms (510,43.6％),economic reasons (476,40.3％) and so on.Conclusion The working status of rural doctors need to befurther improvedand the training need to be strengthened to increase their job satisfaction.
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Objective To observe regular monitoring in patients with chronic myeloid leukemia (CML) who received tyrosine kinase inhibitor (TKI), and to analyze its influencing factors. Methods A total of 857 patients with CML in Henan Tumor Hospital from October 2012 to October 2016 were collected. Patients were told to receive regular monitoring after receiving TKI treatment, including blood routine, bone marrow, BCR-ABL fusion gene and chromosomes. All patients were divided into good and poor compliance groups according to regular monitoring. Chi-square test was used to compare ABL kinase domain mutations rate and mortality between two groups. TKI species, level of education, duration from diagnosis to treatment, teaching times, sites of follow-up, convenience of transportation, annual income and gender were recorded respectively, and the factors affecting regular monitoring were analyzed by using single and multiple factor analysis. Results There were 390 and 467 patients in good and poor compliance groups respectively. Treatment failure rate was 19.49％ (76/390) and 25.91％ (121/467) in good and poor compliance groups respectively, the mutation rate was 28.95％ (22/76) and 7.44％ (9/121) respectively. The difference of ABL kinase domain mutation in patients with treatment failure of both groups was statistically significant (χ 2 =16.287, P < 0.01). The mortality was 0.77％ (3/390) in good compliance group, and 2.78％ (13/467) in poor compliance group, and the difference was statistically significant (χ 2 = 4.543, P = 0.033). The single factors analysis showed that TKI species, level of education, duration from diagnosis to treatment, teaching times, sites of follow-up, convenience of traffic and annual income were related with regular monitoring (all P < 0.05). Multiple-factor analysis showed that inconvenient transportation (β = 1.56, 95％ CI 1.74-3.74, P = 0.014), low education level (β = 1.67, 95％ CI 0.81-3.12, P = 0.041) and low income (β = 2.87, 95％ CI 1.31-4.51, 95％CI 1.74-3.74, P = 0.011) were independent factors for poor compliance in regular monitoring. In the result detection, 56 fusion genes fluctuated. Conclusions CML patients who received regular monitoring have a low treatment failure rate and mortality. Inconvenient transportation, low education level and low outcome are independent risk factors for regular monitoring. The single monitoring result can not prompt treatment effect, and thus it needs to review and monitor for many times.
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Objective To evaluate the efficacy of unrelated donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) for leukemic children .Methods Clinical data of 54 leukemic children undergoing allo-HSCT were retrospectively analyzed from May 2006 to March 2018 .According to the source of donor ,they were divided into matched sibling donor allo-HSCT group (MSD ,n = 27 ) and unrelated donor group (URD ,n= 27) .The clinical outcomes of leukemic children receiving URD allo- HSCT were assessed and those in MSD allo-HSCT group were enrolled as control .Results One patient with refractory AML was not implanted in URD group and the remaining 53 cases were successful in hematopoietic reconstitution .The time of neutrophil and platelet ,the incidence of acute graft-versus-host disease (aGVHD ) , chronic GVHD (cGVHD ) , generalized cGVHD and their transplant-related complications including pulmonary complications ,hemorrhagic cystitis between two groups were not statistically different (P> 0 .05) .The incidence of serious aGVHD ,cytomegalovirus (CMV) and EB virus (EBV) infection was significantly higher in URD group than that in MSD group (P< 0 .05) .The proportion of non-recurrent deaths in URD and MSD groups was 80％ and 31 .3％ respectively and the difference between two groups was statistically significant ( P = 0 .041) .The 3- year disease-free survival rate (DFS) of URD group and MSD group was (52 .9 ± 9 .8 )％ ,(38 .5 ± 8 .7 )％ and the overall 3-year survival rate (OS) was (57 .9 ± 9 .5)％ and (46 .5 ± 9 .7)％ respectively . The inter-group difference was not statistically significant ( P > 0 .05 ) .Conclusions In leukemic children ,although the incidence of complications post URD allo-HSCT is significantly increased , the prognosis is comparable to MSD allo-HSCT .It is a good choice when there is no suitable sibling donor .
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Objective@#To explore the pregnancy outcome and disease status among patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitor (TKI) when they stopped TKI treatment during pregnancy.@*Methods@#The clinical characteristics, reproductive outcomes and disease status of the patients who stopped TKI due to pregnancy between November 2004 to November 2017 were retrospectively collected.@*Results@#A total of 14 CML patients in chronic phase (CML-CP), 12 patients were Sokal-low-risk. The median time of TKI treatment was 46.5 (15-123) months before the drug was stopped. The median age at the time of pregnancy was 29 (24-32) years. The median time of TKI exposure was 4 (0-9) weeks in 12 accidental pregnancies. Outcomes were available for 13 pregnancies, 9 cases (69.2%) delivered healthy babies, 1 case (7.7%) delivered polydactylia malformation baby, 3 cases (23.1%) had spontaneous abortion. The last one was still in pregnancy (no organ malformations were observed in color Doppler ultrasound). At the end of the follow up date, 10 children developed normal, the median age was 14 (0.7-65) months. Of the 14 patients who stopped TKI, 7 in complete molecular response (CMR), 3 in MR4 (BCR-ABLIS <0.01%, ABL transcript >10 000), 2 in major molecular response (MMR), 2 in complete cytogenetic response (CCyR). The median time of TKI discontinuation during pregnancy was 33.5 (4-40) weeks. At the end of pregnancy, 4 cases were in CMR, 4 in MR4, 1 in MMR and 4 in CCyR. No patients lost CCyR and complete hematologic remission.@*Conclusions@#During the treatment of imatinib and Nilotinib, unplanned pregnancy may have a normal infant, but may lead to spontaneous abortion and congenital malformations. Female of CML-CP who had sustained and stable MMR at least 24 months and Sokal-low-risk had higher safety factor discontinued TKI during pregnancy, but still had a risk of increasing tumor load, so monitored the level of BCR-ABL of peripheral blood monthly during pregnancy is necessary.
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Objective@#To explore the occurrence, clinical characteristics, diagnosis and treatment of glomerulitis after allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*Methods@#Analysis were carried out based on the clinical data of 6 patients with de novo glomerulitis following allo-HSCT hospitalized in Henan Tumor Hospital from January 2008 to December 2016, and the clinical manifestation, pathology, diagnosis, treatment and outcome were investigated.@*Results@#The occurrence of glomerulitis was 1.26% (6/478). The median time was 447(272-1 495) d after allo-HSCT. Proteinuria and varying degrees of edema were present in all patients. Of the 6 patients, 4 patients with impaired renal function, 3 cases of hypertension, 5 cases of urine occult blood positive, 2 cases of hyperlipidemia. 5 patients underwent acute graft-versus-host disease (GVHD), 4 patients accompanied with chronic GVHD at diagnosis. Kidney pathology showed typical features of minimal change diseases in 1 patient, membranous nephropathy in 4 patients and mesangial proliferative glomerulonephritis in 1 case. Immunohistochemistry of glomerular lesions revealed that the immune complex deposition included IgG in 4 patients, C3 in 3 patients, IgM and C1q in 1 patient. Serum ANA was positive in 2 patients and serum IgG and IgM were in high level in 1 patient, respectively. Only 1 case was effective on glucocorticoid. 5 cases treated by low dose cyclophosphamide combined with mycophenolate mofetil (MMF), 2 cases achieved complete remission, and 3 cases were partial remission. Up to now, 2 cases died with lung infection, and 4 patients survived.@*Conclusion@#The predominant pathological type of glomerulitis was membranous nephropathy. Low-dose cyclophosphamide combined with MMF was an effective treatment.
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Objective@#To investigate the molecular-cytogenetic characterization and impact on tyrosine kinase inhibitors (TKIs) therapy in chronic phase of chronic myeloid leukemia (CML-CP) patients with variant Ph chromosome (vPh).@*Methods@#The clinical data of 32 patients with vPh chromosomes were collected and compared with 703 patients with typical Ph chromosome in newly diagnosed CML-CP who were on first-line imatinib (IM) and with BCR-ABL transcript of P210.@*Results@#There was no significant difference in demographic and hematological characteristics between vPh and classic Ph patients. 3(9.4%) of the 32 vPh cases were simple variant translocations. Among the remaining 29 cases with complex variant translocations, 28 cases (87.5%) involved 3 chromosomes, and only 1 (3.1%) involved 4 chromosomes. Except for 8, 15, 18, X, and Y chromosomes, the other chromosomes were involved. The frequency of chromosome 12q(15.5%) and 1p (12.1%) were higher involved. The most common FISH signal pattern was 2G2R1Y (74.1%), followed by 1G1R2F (14.8%), 2G1R1Y (3.7%), 1G2R1Y (3.7%), 1G1R1Y (3.7%). The comparison of complete cytogenetic response (CCyR) (P=0.269), major molecular response (MMR) (P=0.391) were carried out between simple and complex mechanisms, without difference. Compared with the classic Ph, the patients with vPh had higher IM primary resistance rate (χ2=3.978, P=0.046), especially primary hematological resistance (χ2=7.870, P=0.005), but the difference of CCyR (χ2=0.192, P=0.661), MMR (χ2=0.822, P=0.365), EFS (χ2=0.509, P=0.476), OS (χ2=3.485, P=0.062) were not statistically significant, and multivariate analysis showed that the presence of vPh did not affect OS (RR=0.692, 95%CI 0.393-1.765, P=0.658)、EFS (RR=0.893, 95%CI 0.347-2.132, P=0.126) and PFS (RR=1.176, 95%CI 0.643-2.682, P=0.703).@*Conclusion@#CML-CP patients with vPh and classic Ph had similar demographic and hematological characteristics. Except for 22q11, 9q34, the frequency of chromosome 12q and 1p were higher involved. The most common FISH signal pattern was 2G2R1Y, and different mechanisms had no impact on TKIs therapy. Compared with cases with classic Ph chromosomes, the patients with vPh chromosomes had higher risk of IM primary resistance, especially primary hematological resistance, which can obtain deeper molecular response quickly after changing to second-generation TKIs and didn’t affect long-term outcomes and OS.
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Objective To summarize the clinical characteristics,diagnosis,treatment and prognosis of EBV related post-transplantation lymphoproliferative diseases (PTLD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods The clinical data of 262 cases of allo-HSCT were retrospectively,and EBV-associated PTLD occurred in 9 cases after transplantation with a incidence of 3.44％ (9/262).Of the 9 patients,6 were males and 3 were females,with a median age of 19 years;the primary disease was severe aplastic anemia (SAA) in 6 cases,acute myeloid leukemia in 2 cases and chronic myeloid leukemia in 1 case Results The occurring median time of EBV associated PTLDs was 58 d (44-271 d).The clinical manifestations of most PTLD recipients were recurrent fever with no reaction to any antibiotics,antiadoncus and lymphadenectasis.Of the 9 recipients,6 cases obtained pathological diagnosis,and 3 cases clinical diagnosis.Superficial lymph node and central nervous system (CNS) involved in 8 and 4 recipients,respectively;lung and bone involvement occurred in 2 recipients and 1 case,respectively.The median number of peripheral blood EBV DNA in 9 recipients was 7.21 × 104 copies/ml (6.37 × 103-4.56 × 105 copies/ml) at the time of onset.EBV DNA in peripheral blood was positive in only one ease of 4 CNS recipients.Among 9 recipients after therapy,4 cases were cured and 4 cases were partially effective,and 1 recipient was ineffective After follow-up for 28 months (2-48 months),6 cases died,and 3 survived.Conclusion Incidence of EBV related PTLD in SAA patients undergoing allo-HSCT is relatively higher than leukemia recipients.Reduction or withdrawal of immunosuppressant,Rituximab and low dose of DLI is effective treatment.
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Objective To study the CT and MRI features of ovarian granulosa cell tumor(OGCT).Methods The clinical and imaging data of 12 cases with OGCT proved by pathology were analyzed retrospectively(10 cases were performed with CT,5 cases were performed with MRI,and 3 cases were performed with both CT and MRI).Results All lesions were solitary.The tumors presented round,oval, or lobulated with clear boundary.In 12 cases, 3 cases were multiple cystic masses with uneven thickness of cyst walls and septation.Mild enhancement of the cyst walls and septation was showed after contrast enhancement.7 cases were cystic and solid masses with multiple cysts, typically with sponge-like pattern,and most cases showed slightly to moderately enhancement.2 cases were solid mass with septation,1 case showed significant enhancement,and 1 case showed slightly enhancement.6 of 12 cases presented enlargement of the utreus and endometrium thickening,1 case was associated with endometrial carcinoma.Conclusion OGCT has characteristic CT and MRI features, and CT and MRI examinations combined with estrogen abnormality are helpful for diagnosis.
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Objective To study the treatment effect by addition of granulocyte-colony-stimulating factor (G-CSF) that could reduce the level of residual disease in patients with Ph-positive chronic myeloid leukemia (CML) who appeared to have achieved a suboptimal response to imatinib (IM) alone. Methods Eleven patients with CML who had achieved≥ 35 % Ph-negativity on treatment of IM were enrolled. The initial dose of imatinib was 400 mg or 600 mg orally daily, and G-CSF, 5 μg/kg subcutaneously daily. The administration of G-CSF was postponed or interrupted in the event of leukocytosis (leukocytes ≥ 30 ×109/L) until the whitecell count fell ＜20 × 109/L. Efficacy was assessed by serial monitoring of blood levels of bcr-abl transcripts.Treatment with G-CSF was discontinued if the patient did not achieve a reduction in the transcript level of at least 0.5 log after 6 months. For patients whose bcr-abl transcript levels continued to decline but had not yet reached molecular remission, treatment was designed to continue for 1 to 6 months. Results Of 11 evaluable patients, nine had an appreciable decline in bcr-abl transcript levels(include 7 cases the reduction was greater than 1 log and 2 cases the reduction was greater than 0.5 log), 2 cases the reduction was lower than 0.5 log.In 7 cases the reduction was greater than 1 log, including five patients who did not achieved complete cytogenetic response and two patients achieved complete molecular responses. No bleeding episodes occurred.No patient discontinued therapy because of toxicity and there were no treatment-related deaths. Conclusion The addition of G-CSF should be considered safely and successfully for patients who fail to obtain optimal response to IM alone and this approach deserves further evaluation.
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Objective Study the relationship between type A influenza virus genetic variation with survival selective pressure, help for the finding of possible vaccine conserved antigen target. Methods Select seven strains of same HA (Hemagglutinin) serotype, regional and isolation time closely related type A influenza virus with full HA gene coding sequence; use Blast2 program to calculate the parameter of nucleotide conservative, amino acid conservative, mutation ratio of codon 3rd (over) non 3rd locus, survival selective pressure indicator of these virus strains; analysis the parameters relationship with survival selective pressure indicator. Results Nucleotide conservative of HA gene is significantly lower than that of other genes; amino acid conservative of HA gene is similar with NS gene, all lower than that of other genes; genetic variation of HA gene is under survival selective pressure; selective pressure toward NS, PB1 gene is relatively lower than that toward NA, NP gene; survival selective pressure indicator is strongly correlated with mutation frequency upon codon 3rd locus. Conclusions Genetic variation of influenza virus is determined both by mechanism of relax replication model and survival selective pressure; genetic conservative of each gene is different, NA, NP gene could be selected as possible vaccine target for their relative high conservative, HA gene possesses medium genetic conservative with prospective of finding more conserved epitope region within its full sequence, NS, PB1 are not recommended as vaccine candidate for their relative low genetic conservative.