Objective To study the clinical outcome of patients with fns-like tyrosine kinase-3internal tandem duplication (FLT3-ITD) positive acute myeloid leukemia (AML) treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) and to explore the potential prognostic factors to patients' survival including transplant types or disease status.Methods A total of 314 AML patients in our center from October 2006 to October 2012 were retrospectively analyzed,among whom,54 patients were defined with FLT3-ITD positive.Survival rates and treatment-related mortality were further analyzed.Results For all 54 FLT3-ITD positive patients,the 3-year overall survival (3-OS) rate was 56％ and 3-year leukemia-free survival (3-LFS) rate was 47％.The outcome of haplo-identical HSCT was similar as that of sibling donors(3-OS rate:60％ vs 54％ ; 3-LFS rate:54％ vs 45％,respectively).There were 47 patients who received transplantation in first complete remission(CR1).The other 7 patients were of disease relapse or in CR2 before transplantation.Not surprisingly,patients in CR1 had better prognosis than those in nonCR1.Conclusions Allo-HSCT is an effective treatment for AML patients with FLT3-ITD positive mutation.The survival outcome of haplo-identical HSCT was comparable with that of sibling donors.Relapse of AML was the dominant factor related to the mortality of FLT3-ITD positive AML patients after allo-HSCT.

Objective To examine the value ofprocalcitonin (PCT) in differential diagnosis of bloodstream infections (BSI) caused by coagulase-negative Staphylococcus (CNS) from contamination in Department of Hematology.Methods One hundred and fifty-six patients with bloodstream or intravenous catheter-related CNS infection were included in this study.The patients were treated in Department of Hematology,the First Affiliated Hospital of Soochow University during the period from January 2013 to December 2015.The patients were divided into CNS bloodstream infection group (n=66) and blood culture contamination group (n=90).The two groups were compared in terms of sex,age,diagnosis,length of hospital stay,duration of neutropenia,neutrophil count and lymphocyte count,peak fever,C-reactive protein (CRP) and PCT.The receiver operating characteristic (ROC) curve was plotted with SPSS 21.0 software to analyze the value of PCT in differential diagnosis.Results Age,sex,clinical diagnosis,length of hospital stay,duration of neutropenia,neutrophil count and lymphocyte count did not show significant difference between bloodstream infection group and contamination group (P＞0.05),while peak fever (P＜0.001),CRP (P=0.002) and PCT (P=0.018) were significantly higher in bloodstream infection group than in contamination group.ROC analysis indicated that PCT provided optimal discrimination between these two groups at cnt-offvalue of 0.374 μg/L,with sensitivity of 54.5％ and specificity of 94.4％.The area under the curve (AUC) was 0.830±0.032 (95％ CI:0.767-0.893,P＜0.001).Conclusions PCT may be a good marker for differentiating CNS bloodstream infection from contamination with higher specificity than the commonly used marker CRP.This finding may help clinicians reduce the overuse of antibiotics.

Objective:To investigate the incidence, risk factors and survival of cGVHD patients in combination of a haploidentical donor supported with an unrelated umbilical cord blood for hematopoietic stem cells transplantation (haplo-cord-HSCT).Methods:300 hematological malignancies individuals who received dual transplantation were enrolled in the study between January 2012 and July 2016 at the department of Hematology in the First Affiliated Hospital of Soochow University. The clinical diagnosis and scoring the severity of cGVHD syndromes according the National Institutes of Health (NIH) consensus conference in the 2014 update. Cox proportional hazards regression was used to identify risk factors associated with transplant outcomes.Results:During follow-up with a median time of 26.4 months (range 0.2-61.8) post transplantation, the 1-year, 3-year and 5-year cumulative incidence of cGVHD was 26.3 % (95 % confidence interval [CI], 23.5 %~29.1 %), 30.3 % (95 % CI, 27.3 %~33.3 % ) and 32.2 % (95 % CI, 28.7 %~35.7 %). For all 73 patients with cGVHD, first-line or second-line treatment were given. During the follow-up period, 53 patients survived, and 20 patients died. In multivariate analysis, the cGVHD overall survival (GOS) were associated with thrombocytopenia(<100×109/L)(HR=0.103, 95 % CI 3 %-36.1 %, P<0.001). Conclusions:Our data suggest that, the 5-year cumulative incidence of cGVHD was 32.2 % after haplo-cord-HSCT with hematological malignancies. Thrombocytopenia (<100×109/L)was independent risk factors for GOS.

Objective:To evaluate the role of c-Abl in myocardial ischemia-reperfusion (I/R) injury in diabetic rats.Methods:Sixty male SPF-grade healthy Sprague-Dawley rats, aged 7-9 weeks, weighing 210-230 g, were divided into 6 groups by a random number table method: sham operation group (S group, n=6), myocardial I/R group (IR group, n=12), diabetic sham operation group (DS group, n=6), diabetic myocardial I/R group (DIR group, n=12), diabetic myocardial I/R plus AVV9-siRNA-c-Abl group (DIR+ c-Abl group, n=12), and diabetic myocardial I/R plus AVV9-GFP group (DIR+ GFP group, n=12). One percent streptozotocin 60 mg/kg was intraperitoneally injected to induce type 1 diabetes mellitus.AVV9-siRNA-c-Abl and AVV9-GFP 1×10 12 mg/kg were slowly injected at 4 weeks after establishing the model in DIR+ c-Abl and DIR+ GFP groups.Myocardial ischemia was induced by 30 min occlusion of left anterior descending branch (LAD) of coronary artery followed by 2 h reperfusion at 8 weeks after establishing the model.At the end of reperfusion, left ventricular systolic pressure (LVSP) and the maximum rate of increase and decrease of left ventricular systolic pressure (±dp/dt max) were monitored, and blood samples were collected for determination of the concentrations of serum lactic dehydrogenase (LDH) and creatine kinase-MB (CK-MB) (by enzyme-linked immunosorbent assay)and myocardial infarct size (except group S and group DS). Myocardial tissues were obtained for determination of the apoptosis index of cardiomyocytes(by TUNEL staining), expression of c-Abl, p53 and activated caspase-3 (by Western blot), and binding of c-Abl and p53 (c-Abl/p53) (by co-immunoprecipitation method). Results:LVSP and ±dp/dt max were significantly decreased, serum LDH and CK-MB concentrations were increased, apoptosis index and c-Abl/p53 were increased, and the expression of c-Abl, p53 and activated caspase-3 was up-regulated in group IR when compared with group S and in group DIR as compared with group DS ( P<0.05). Compared with group DIR, the LVSP and ± dp/dt max were significantly increased, serum LDH and CK-MB concentrations were decreased, myocardial infarct size was decreased, apoptosis index and c-Abl/p53 were decreased, and the expression of c-Abl, p53 and activated caspase-3 was down-regulated in group DIR+ c-Abl ( P<0.05), and no significant change was found in the parameters mentioned above in group DIR+ GFP ( P>0.05). Conclusion:c-Abl is involved in the pathophysiological process of myocardial I/R injury probably by activating p53 signaling pathway in diabetic rats.

BACKGROUND:Vertigo is closely related to clinical neurological disorders.When neurons are damaged or dead,it may lead to abnormalities in the vestibular system and trigger vertigo symptoms.Therefore,it is necessary to explore and analyze the hotspots related to vertigo that are common in clinical neurology. OBJECTIVE:To analyze the vertigo-related histopathological changes in clinical neurology and the research hotspots worldwide using bibliometric methods. METHODS:The WanFang database and Web of Science core set database were searched by the first author to retrieve the research-related literature published from 2014-2023 on the treatment of common vertigo in clinical neurology.A bibliometric analysis of the number of publications,country/region,institution,keywords,co-cited literature,and highly cited literature was peformed using VOSviewer_1.6.19 software to summarize the research hotspots in this research field. RESULTS AND CONCLUSION:Web of Science core set database had the highest number of 174 publications in this field in 2022,and WanFang database had the highest number of 133 publications in this field in 2020.The top 3 countries with the highest number of publications are the United States,Germany,and China.The University of Munich,Germany is the international institution with the highest number of publications in this field,while Chengdu University of Traditional Chinese Medicine is the Chinese institution with the highest number of publications in this field.The results of keyword analysis showed that the research hotspot diseases in this field in China are mainly Meniere's disease,cervical vertigo,senile vertigo,benign paroxysmal positional vertigo,isolated vertigo,and hypertensive vertigo,and the treatments include acupuncture,rehabilitation,medication(gastrodin,Banxia Baizhu Tianma Tang),and manipulative reduction.International research hotspot diseases in this field mainly include benign paroxysmal positional vertigo,vestibular disorders in new coronavirus cases,Meniere's disease,vestibular schwannoma,acoustic neuromas,and vestibular migraines,etc.,and the hotspot treatments are antivertiginous medications,antidepressant and anxiolytic treatments,and microsurgery.The results of literature co-citation analysis showed that for acute vestibular syndrome with persistent vertigo as the main symptom,three-step bedside ophthalmoscopy(HINTS:Head-Impact-Nystagmus-Strabismus Test)is more sensitive than early MRI in the diagnosis of combined strokes in patients with acute vestibular syndrome,which is the most peer-recognized method of detecting strokes in vestibular syndrome,whereas hormonal therapy is more effective to treat vestibular neuritis patients with paroxysmal vertigo as the main symptom.The results of highly cited literature analysis showed that,in the hot literature included in WanFang database in the past 10 years,acupuncture at Fengchi point and the acupuncture method of inducing resuscitation to improve posterior circulation ischemic vertigo have achieved certain results.The literature published in the past 3 years has indicated that Ginkgo biloba leaf extract+gastrodin,acupuncture+Banxia Baizhu Tang,betahistine+gastrodin,vestibular rehabilitation training+Epley Maneuver,all can improve the vertigo symptoms to different degrees.While there were no featured anti-vertigo drugs indicated in the literature in the Web of Science core set data in the recent 10 years,and most of them are based on traditional anti-vertigo drugs and microsurgery.However,there are a few case reports in the international literature in the last 3 years that found that COVID-19 infection may lead to vestibular neuritis and vertigo symptoms.The onset and progression of vertigo may be closely related to neuronal damage and regeneration.For example,viral infections,inflammatory stimuli,or other pathologic factors may lead to neuronal damage or death,thereby affecting the function of the vestibular system.Vertigo-related diagnosis and treatment standardization guidelines have been published both domestically and internationally.Currently,international guidelines recommend the combination of vestibular rehabilitation and physical rehabilitation for the treatment of vertigo,and Chinese guidelines recommend the combination of Chinese and Western medicine,reduction and acupuncture.However,the level of evidence is not very high,so a large number of large-sample,multicenter randomized controlled trials on anti-vertigo treatment are needed in the future.

Objective:To investigate the mid-term clinical outcomes of arthroscopic vertical mattress suturing for shoulder recurrent anterior dislocation combined with joint laxity.Methods:A retrospective case series study was performed on the clinical data of 11 patients with recurrent anterior shoulder dislocation combined with joint laxity admitted to the First Affiliated Hospital, Army Medical University from January 2018 to September 2021. The patients included 10 males and 1 female, aged 18-38 years [(22.8±5.5)years]. All the patients received treatment with arthroscopic vertical mattress suturing. The Oxford shoulder instability score, Rowe shoulder instability score, and simple shoulder test (SST) score were compared before operation, at 6 months after operation and at the final follow-up. The degree of joint capsule laxity and length of capsular redundancy (evaluated by MRI) were compared before operation and at the final follow-up. The results of the supine apprehension test, re-dislocation and postoperative complications such as iatrogenic vascular and nerve injuries were observed at the final follow-up. Also, the correlation between the radiological changes in the joint capsule and the shoulder function was analyzed by Spearman correlation coefficient.Results:All the patients were followed up for 20-64 months [(40.7±18.6)months]. Before operation, at 6 months after surgery and at the final follow-up, the values of Oxford shoulder instability score were (41.2±4.7)points, (49.5±3.0)points and (57.6±3.0)points; the values of Rowe shoulder instability score were (28.6±9.5)points, (77.7±7.2)points and (94.1±10.9)points; and the values of SST score were (7.6±1.3)points, (9.8±1.0)points and (11.6±0.9)points, respectively. The Oxford shoulder instability score, Rowe shoulder instability score and SST at 6 months after operation and at the final follow-up were significantly better than those before operation, and those at the final follow-up were significantly better than those at 6 months after operation (all P<0.05). The MRI showed that the degree of joint capsular laxity and length of capsular redundancy were 1.5±0.2 and (19.7±2.5)mm before operation and were 1.3±0.2 and (12.9±3.7)mm at the final follow-up, respectively ( P<0.05 or 0.01). The supine apprehension test was negative at the final follow-up, with no re-dislocation or postoperative complications such as iatrogenic vascular or nerve injuries. Correlation analysis showed a negative correlation between the degree of joint capsular laxity and the Oxford shoulder instability score ( r=-0.62, P<0.05) and that of the length of capsular redundancy with the Oxford shoulder instability score ( r=-0.80, P<0.01), the Rowe shoulder stability score ( r=-0.73, P<0.01) and the SST score ( r=-0.75, P<0.01). Conclusions:Arthroscopic vertical mattress suturing has good mid-term clinical outcome for recurrent shoulder anterior dislocation combined with joint laxity, improving the shoulder function and reducing complications, wihch is associated with decreased joint capsule laxity and length of capsular redundancy.

OBJECTIVETo clarify the clinical, cytogenetical and molecular characteristics and prognosis of Ph(+) ALL patients with ABL kinase domain mutations (ABL-KDMs), and to evaluate the therapeutic value of allogeneic hematopoietic stem cell transplantation (allo-HSCT) combined with tyrosine kinase inhibitor (TKI) in these patients.

METHODSRetrospective analysis of clinical features, molecular genetic characteristics, mutation distribution and prognosis of newly diagnosed Ph(+) ALL patients with ABL-KDMs from February 2010 to August 2014 were performed, and the efficacy of treatment regimen of allo-HSCT combined with different TKIs was compared.

RESULTSOf 88 Ph(+) ALL patients during maintenance treatment stage for ABL-KDMs monitoring, mutation was detected in 42 patients with median time of 8 months from diagnosis to mutation occurrence. The median age of mutation group was 40-year-old, older than that of non-mutation group (32.5-year-old) (P=0.023). The incidence of complex chromosome abnormality of mutation group was higher than that of non-mutation group (P=0.043), with alternations in chromosome 7, 5 and +Ph more frequently observed. There were 21 types of mutation at 18 locations detected, with T315I mutation ranking the top followed by E255K/V, Y253H/F and E459K. Mutation group featured no significant difference in complete remission (CR) rate in contrast to nonmutation group, but was remarkably lower in major molecular remission (MMR) rate than non-mutation group. The 2 year and 5 year overall survival rate of mutation group was 45.4% and 35.0% respectively, much shorter than that of non-mutation group (67.8% and 63.3%), (P=0.047). The median survival of patients with T315I and E255K/V was 19 and 10 months, significantly shorter than that of patients with other mutations. Among the 42 patients with mutations, 14 underwent allo-HSCT, and the median survival was 29 months, longer than that of patients received chemotherapy alone (17 months) (P=0.024). Fourteen allo-HSCT patients were given nilotinib or dasatinib at the time of mutation occurrence, and there was no significant difference in the overall survival in contrast to patients who continue to take imatinib.

CONCLUSIONSABL kinase domain mutations are closely related to the older age and high genomic instability in the newly diagnosed Ph(+) ALL patients. Mutation types showed diversity and complexity, which remarkably affected patients' prognosis and survival. T315I and E255K mutations account for more than half of all cases, characterized by a less favorable prognosis. Currently, allo-HSCT is the only method that has the potential of elongating life expectancy, but the utility of second-generation TKI during relapse does not necessarily have an edge on survival over imatinib.

Chromosome Aberrations ; Dasatinib ; therapeutic use ; Hematopoietic Stem Cell Transplantation ; Humans ; Imatinib Mesylate ; therapeutic use ; Mutation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; genetics ; Prognosis ; Protein Kinase Inhibitors ; therapeutic use ; Proto-Oncogene Proteins c-abl ; genetics ; Pyrimidines ; therapeutic use ; Remission Induction ; Retrospective Studies ; Survival Rate

Objective To investigate the monitoring significance of WT1 gene level in the prognosis of acute myeloid leukemia (AML) patients with normal karyotype after hematopoietic stem cell transplantation (HSCT). Methods The clinical data of 115 AML patients with normal karyotype who were treated with HSCT from July 2009 to March 2017 in the First Affiliated Hospital of Soochow University were retrospectively analyzed. The dynamic detection of bone marrow WT1 gene was carried out by using reverse transcription_polymerase chain reaction (RT_PCR). According to the relative expression level median of WT1 gene before transplantation, the whole patients were divided into the two groups (

Objective: To investigate the efficacy of first-line administration of generic dasatinib or first-generation TKI (imatinib) in patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph⁺ ALL) treated by hematopoietic stem cell transplantation (HSCT). Methods: Clinical features and prognoses of 63 newly diagnosed Ph⁺ ALL patients from Jan 2014 to June 2017 treated by HSCT combined with first-line administration of generic dasatinib or imatinib were retrospective analyzed. Results: Of 63 Ph⁺ ALL patients, 31 cases were administered generic dasatinib, and the other 32 ones imatinib. Complete remission (CR) rates at the fourth week of induction therapy in generic dasatinib and imatinib groups were 96.8% and 93.8% (P=1.000) , respectively. Meanwhile major molecular response (MMR; BCR-ABL/ABL reduce 3log) rates were 41.9% and 43.8% (χ²=0.021, P=0.884), respectively. Relapse rates before transplantation were 6.5% and 12.5% (P=0.672), respectively. MMR rates before HSCT were 83.9% and 68.8% (χ²=1.985, P=0.159), respectively. The 20-monthes overall survival (OS) rates of generic dasatinib and imatinib groups were 95.5% and 76.5% (χ²=0.990, P=0.320) respectively; 20-monthes event-free survival (EFS) rates were 93.5% and 61.4% (χ²=5.926, P=0.015), respectively. Statistically significant differences of EFS were reached. Multiple factors analysis showed that generic dasatinib (HR=0.201, 95% CI 0.045-0.896, P=0.035) and MMR before transplantation (HR=0.344, 95% CI 0.124-0.956, CI=0.041) could improve EFS. Conclusions First-line administration of generic dasatinib could improve EFS for Ph⁺ALL patients treated by HSCT when compered with imatinib.

Objective:To compare the mid-term clinical outcomes between traumatic stiff shoulder and frozen shoulder after arthroscopic capsule release combined with subacromial space recovery.Methods:From January 2014 to December 2019, 55 patients were treated at Sports Medicine Center, The First Affiliated Hospital, Army Medical University for limited range of shoulder motion. Of them, 22 suffered from traumatic stiff shoulder (7 males and 15 females) (group A) and 33 from frozen shoulder (10 males and 23 females) (group B). All patients were treated with arthroscopic 270° capsule release combined with subacromial space recovery. Shoulder pain was evaluated by visual analogue scale (VAS) and shoulder function by Constant score before operation and at the final follow-up. The 2 groups were compared in improvements in flexion, abduction, external rotation and internal rotation of the shoulder.Results:No significant difference was observed between the 2 groups in gender, age, course of disease, preoperative internal rotation or external rotation of the shoulder ( P>0.05). Preoperative VAS score [2.5(2.0, 3.3) points] and Constant score [(33.7±9.6) points] in group A were significantly lower than those in group B [4.0(3.0,5.5) points and (45.8±12.3) points] ( P<0.05). No complication like infection or nerve injury was found during follow-ups. All the incisions healed at the first stage. The follow-up time averaged 37.0 months (from 20 to 79 months). At the last follow-up, VAS scores [1.0(1.0, 1.0) points and 1.0(1.0, 1.0) points] and Constant scores [(87.0±3.2) points and (85.7±4.3) points] for both groups were significantly improved compared with their preoperative values [2.5(2.0,3.3)分points and 4.0(3.0,5.5) points for VAS; (33.7±9.6) points and (45.8±12.3) points for Constant score] ( P<0.05). Compared with preoperation, the improvements at the last follow-up were 99.3°±19.9° and 83.3°±27.7° in shoulder anteflexion and 102.0°±21.5° and 83.9°±32.8° in abduction for groups A and B, with greater improvements in group A; the improvements in VAS score for groups A and B were 1.0(1.0, 2.3) points and 3.0(2.0, 4.5) points, with greater improvements in group B; the improvements in Constant score were (53.3±9.5) points and (39.8±12.9) points for groups A and B, with greater improvements in group A. The above comparisons all showed a significant difference between the 2 groups ( P<0.05). Conclusions:Arthroscopic 270° capsule release combined with subacromial space recovery can lead to good mid-term clinical outcomes similar for both traumatic stiff shoulder and frozen shoulder. However, the improvements in flexion, abduction and Constant score may be greater for traumatic stiff shoulder than for frozen shoulder.