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Objective:To explore the characteristics of BCR-ABL1 kinase domain mutations in imatinib-resistant chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) patients from Northeast China and their impact on prognosis. Methods:The clinical data of 252 CML patients and 49 Ph + ALL patients who were admitted to the First Hospital of Jilin University from January 2013 to October 2018 were retrospectively analyzed. The samples of bone marrow or peripheral blood were collected from patients when imatinib treatment was not effective. Nested polymerase chain reaction (PCR) was used to amplify the BCR-ABL1 kinase domain, and Sequencing Analysis v5.4 software was used to analyze the mutation of BCR-ABL1 kinase domain. Patients were followed up for 6-48 months, and the survival analysis was performed. Results:Among 252 CML patients, the mutations in ABL1 kinase domain were found in 57 patients (22.6%), including 25 patients in the chronic phase, 21 patients in the accelerated phase and 11 patients in the blast crisis; 50 patients had 20 types of single point mutation, and the most common mutation types were E255K (16.0%, 8/50), T315I (14.0%, 7/50), M244V (8.0%, 4/50) and G250E (8.0%, 4/50), which were all concentrated in the P-loop and C-helix domains; 7 patients had double mutations; patients with multiple mutations had the worst prognosis, with a median overall survival (OS) time of 3.2 months. Among 49 Ph + ALL patients, 17 cases (34.7%) were positive for mutations in the BCR-ABL1 kinase domain, 14 patients had 12 types of single point mutation, and 3 patients had multiple mutations; the median OS time of patients with multiple mutations, mutations located in the P-loop and C-helix domains and mutations located in the other domains was 2.0, 8.0 and 18.0 months, and the difference in OS among the three groups was statistically significant ( P < 0.01). Conclusions:Among the imatinib-resistant CML and Ph + ALL patients from Northeast China, point mutations in the P-loop and C-helix domains are most commonly found. Multiple mutations, mutations in the P-loop and C-helix domains are related to the poor prognosis of the patients.
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Objective:To investigate the clinical characteristics and prognosis of acute myeloid leukemia (AML) patients with positive TLS-ERG fusion gene.Methods:The clinical data of 9 AML patients with positive TLS-ERG fusion gene in the First Hospital of Jilin University from June 2013 to August 2020 were retrospectively analyzed, and the relevant literature was reviewed.Results:Among 9 patients with positive TLS-ERG fusion gene, there were 5 males and 4 females, with a median age of 16 years old (6-40 years old). Five patients received chemotherapy alone, 3 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), and 1 patient did not receive systematic treatment. Among 8 patients with systematic treatment, 1 patient had complete remission after the first induction chemotherapy and 5 patients had complete remission after induction therapy. The median overall survival time of 5 patients with chemotherapy alone was 1.5 months (1-11 months), of which 3 patients did not respond to the first course of treatment and died of infection, and 2 patients died after relapse. The median overall survival time of 3 patients with allo-HSCT was 16 months (13-17 months), of which 2 patients died after relapse and 1 patient had sustained molecular complete remission by the end of follow-up.Conclusions:AML with positive TLS-ERG fusion gene has low incidence rate and poor induction efficacy. Hematopoietic stem cell transplantation may partially improve the survival prognosis of patients, but it cannot overcome the adverse effect of positive TLS-ERG fusion gene on prognosis.
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Chronic myeloid leukemia (CML) is a malignant tumor formed by clonal proliferation of bone marrow hematopoietic stem cells. With the improvement of disease awareness and the introduction of new drugs, more than 90% of CML patients can achieve long-term survival. However, a few patients still show drug resistance. This article reviews the mechanism of drug resistance in CML patients treated with tyrosine kinase inhibitor (TKI) and the characteristics of ABL kinase region mutation.
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Objective:To explore the effect of intermittent theta-burst stimulation (iTBS) of the cerebellum on the excitability of the M1 zone in the bilateral motor cortex and the duration of any effect.Methods:Twenty healthy youths were randomly assigned to a left or a right cerebellum iTBS group, each of 10. The resting motor threshold and motor evoked potential (MEP) of the motor cortex were determined before giving 600 pulses of iTBS. Then MEP was measured at the 5th, 10th, 15th, 20th, 25th, 30th, 35th and 40th minute after the intervention ended. Any changes in MEP amplitude were also analyzed.Results:①The average MEP amplitude in the right motor cortex had increased significantly in the left cerebellum iTBS group from the 5th to the 15th minute. The increase lasted at least 10 minutes. Then it had returned to the baseline value at the 35th minute. ②The MEP amplitude in the left motor cortex decreased slightly after iTBS of the left cerebellum began, but there were no significant changes. ③The MEP amplitude in the left motor cortex had a tendency to decrease after iTBS was administered to the right cerebellum, but that change too was not significant. ④The MEP amplitude of the right motor cortex decreased significantly only for the first 30 minutes.Conclusions:iTBS of the cerebellum can increase the excitability of the contralateral motor cortex. The effect can last 25 minutes. It can also decrease the excitability of the ipsilateral motor cortex for 30 minutes.
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Objective:To investigate any change in the effective connectivity between the bilateral anterior central gyruses after transcranial magnetic stimulation (TMS).Methods:Twenty-one healthy subjects were examined using resting state functional magnetic resonance imaging (rs-fMRI) before and after receiving continuous theta burst stimulation (cTBS). The brain atlas of the Institute of Automation of the Chinese Academy of Sciences was used for fine partitioning of the bilateral anterior central gyruses. Granger causality analysis was used to compare any changes in the effective connectivity between them.Results:After the cTBS inhibited the right M1 area, significant changes in effective connectivity among the sub-regions of the bilateral M1 area were observed. The effective connectivity of the right upper limb to the left upper limb and the left head to face were weakened, while that of the left upper limb to the right head, as well as of the face to the right upper limb was enhanced.Conclusion:For people whose right M1 area has been inhibited by cTBS, the effective connectivity changes in both upper limb functional areas of the M1 region reflect inter-hemispheric inhibition. Opposite changes were found in the trunk and upper limbs.
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Objective:To explore the effectiveness of evaluating voice disorders in dysarthria patients after brain injury using speech production measurements and analyze their phonics characteristics.Methods:Twenty-nine patients were divided into a severe dysarthria group ( n=19) and a mild dysarthria group ( n=10) through the subjective evaluation of their speech, and then evaluated using a computer speech monitor. The maximum phonation time (MPT), maximum counting ability (MCA), basic frequency (F0), standard deviation of F0 (F0SD), F0 range, intensity, formant, and the distance of jaw and tongue movements were recorded. Results:All of the patients displayed abnormal MPTs and MCAs, with the average MPT and MCA of the severe dysarthria group significantly lower than the mild group′s averages. In the severe dysarthria group, the abnormal F0s, F0SDs, F2(i)s and tongue movement distances were significantly greater than in the mild group.Conclusions:Speech production measurements can be applied to evaluate the speech dysarthria patients after brain injury. It is very common for such patients to have impaired speech and respiratory function, so this is worthy of attention.
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Objective@#To investigate the current status and real performance of the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels in China through interlaboratory comparison.@*Methods@#Peking University People’s Hospital (PKUPH) prepared the samples for comparison. That is, the fresh RUNX1-RUNX1T1 positive (+) bone morrow nucleated cells were serially diluted with RUNX1-RUNX1T1 negative (-) nucleated cells from different patients. Totally 23 sets with 14 different samples per set were prepared. TRIzol reagent was added in each tube and thoroughly mixed with cells for homogenization. Each laboratory simultaneously tested RUNX1-RUNX1T1 and WT1 transcript levels of one set of samples by real-time quantitative PCR method. All transcript levels were reported as the percentage of RUNX1-RUNX1T1 or WT1 transcript copies/ABL copies. Spearman correlation coefficient between the reported transcript levels of each participated laboratory and those of PKUPH was calculated.@*Results@#①RUNX1-RUNX1T1 comparison: 9 samples were (+) and 5 were (-) , the false negative and positive rates of the 20 participated laboratories were 0 (0/180) and 5% (5/100) , respectively. The reported transcript levels of all 9 positive samples were different among laboratories. The median reported transcript levels of 9 positive samples were from 0.060% to 176.7%, which covered 3.5-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.5 to 12.3 (one result which obviously deviated from other laboratories’ results was not included) , 85% (17/20) of the laboratories had correlation coefficient ≥0.98. ②WT1 comparison: The median reported transcript levels of all 14 samples were from 0.17% to 67.6%, which covered 2.6-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.3-13.7, 62% (13/21) of the laboratories had correlation coefficient ≥0.98. ③ The relative relationship of the reported RUNX1-RUNX1T1 transcript levels between the participants and PKUPH was not always consistent with that of WT1 transcript levels. Both RUNX1-RUNX1T1 and WT1 transcript levels from 2 and 7 laboratories were individually lower than and higher than those of PKUPH, whereas for the rest 11 laboratories, one transcript level was higher than and the other was lower than that of PKUPH.@*Conclusion@#The reported RUNX1-RUNX1T1 and WT1 transcript levels were different among laboratories for the same sample. Most of the participated laboratories reported highly consistent result with that of PKUPH. The relationship between laboratories of the different transcript levels may not be the same.
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Objective To explore the effect of action verb processing on the excitability of the motor cortex and any effect on the upper limb motor function of stroke survivors.Methods Experiment 1:The motor evoked potential by transcranial magnetic stimulation (TMS-MEP) was measured while 18 healthy subjects were processing concrete action verbs or abstract verbs.Experiment 2:Eight hemiplegic stroke survivors were asked to read silently text describing concrete hand actions,and then repeat and explain the meaning of the action verbs used in the text.This was repeated for 30 minutes per day,5 days per week for 3 weeks.In the 2nd week the same training was conducted except that the text was about abstract verbs.The modified Ashworth scale (MAS),Fugl-Meyer assessment (FMA),the Hong Kong version of the functional test for a hemiplegic upper extremity (FTHUE-HK) and a simple test for evaluating hand function (STEF) were used to assess upper limb motor function before and after the training each week.Results Experiment 1:Processing the concrete action verbs induced significantly greater MEP than processing the abstract verbs.Experiment 2:The average FMA and STEF ratings improved significantly after the training each week.Training with the concrete action verbs resulted in significantly better FMA and STEF scores than with the abstract verbs.The average MAS score increased significantly week by week.There was significantly more improvement in the average FTHUE-HK rating after the 1st and 3rd week of training than after the 2nd week.Conclusion Action verb processing induces greater motor cortex excitation than abstract verb processing among healthy subjects and better improves the upper limb motor function of stroke survivors.
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Objective:To determine the derivative chromosome 9 by the method of detecting the ASS gene,and to explore the relationship between the deletion of derivative chromosome 9 and the efficacy and prognosis of the chronic myeloid leukemia (CML)patients. Methods:The materials of 34 CML patients with positive BCR-ABL fusion gene whose ASS genes were detected were retrospectively analyzed. All patients were treated with Extra-signal (ES)probe to detect the derivative chromosome 9.All patients were divided into two groups according to whether they carried the derivative chromosome 9.The blastic phase or the accelerated phase rates in two groups were compared by using Fisher exact probability. Results:All patients were detected by FISH (BCR-ABL ES probe),and all the BCR-ABL fusion signals were positive.6 of 34 patients were found the deletion of ASS gene, among them 1 case blonged to chronic phase,and 5 cases developed into blastic phase or accelerated phase. In the patients without ASS gene deletion,there were 22 cases in chronic phase,and 6 cases in plastic phase or accelerate phase,there was significant difference of blastic phase rate/accelated phase rate between them (P 0.05 ). Conclusion:The CML patients with derivative chromosome 9 (ASS gene deletion)prone to get disease progression, and have a higher proportion in the blastic phase or accelerated phase patients.Derivative chromosome 9 is related to the bad treatment efficacy of TKI and the poor prognosis of CML.
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Objective To explore the clinical characteristics and prognosis of acute myeloid leukemia (AML) patients with CCAAT/enhancer binding protein α (CEBPA) mutations.Methods 208 patients with de novo AML were retrospectively analyzed with regard to frequency of CEBPA mutations,clinical characteristics,therapeutic response and long-term outcome.Results CEBPA mutations were detected in 37 patients (17.8 ％),with 29 cases of double mutations and 8 cases of single mutation.In 117 cases of patients with normal karyotype,28 cases (23.9 ％) were detected with CEBPA mutations.As compared with no CEBPA mutation,the following characteristics were observed in patients with CEBPA double mutations.Presented with younger age at diagnosis,82.8 ％ (24/29) of the patients were M1 and M2.Presented with higher peripheral white blood cell count,higher hemoglob in and low platelet count.And increases of CD7,CD34 and HLA-DR expression.Compared with those without mutation,patients with biCEBPA mutations had better overall survival (OS) (2-years OS:100 ％ vs 75.1％,P =0.045).Conclusion BiCEBPA mutation is one of the favorable prognosis indicators.
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Music and speech may share the same neural pathway, and the role of music therapy in speech rehabilitation gradually at-tracts the attention from the rehabilitation medical profession in recent years. This article reviewed the effect, mechanism, and strategy of music therapy in speech rehabilitation.
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@#Objective To study the effect of stilbene on blood glucose of rats with type 2 diabetes. Methods 50 male Wistar rats wererandomly divided into model group (n=40) and control group (n=10). The model group was given fat emulsion 40 days continuously with 20ml/kg, po, and streptozotocin with 120 mg/kg on the 41st day, 100 mg/kg on the 42nd day, i.p. After the modeling, the model group was dividedinto 4 groups with 10 in each. They were given stilbene with 500 ml/kg, 200 ml/kg, 100 ml/kg and metformin with 100 mg/kg, ip, respectively.The level of blood glucose, blood lipid and glycogen content were determined. Results After the modeling, the blood glucoseand TG, TC, LDL-C, HDL-C increased by 140.89%, 25.77%, 275.52%, 105.54% and 31.25% respectively (P<0.01); after stilbene was given,the level of blood glucose and lipid decreased significantly (P<0.05), the liver glycogen content increased significantly by 8.06%~16.17% compared to the control group. Conclusion Stilbene can decrease the concentration of blood glucose and lipid, and increase the liverglycogen content of rats with type 2 diabetes.