OBJECTIVETo assess the value of multiprobe fluorescence in situ hybridization (FISH) panel in the diagnosis of acute myeloid leukemia (AML).

METHODSThe multiprobe AML/MDS panel comprising 8 different FISH probes for AML1/ETO transfusion gene, PML-RARα transfusion gene, CBFβ/MYH11 transfusion gene, MLL breakapart, P53 deletion, Del(5q), -7/Del(7q), and Del(20q) was tested in 40 cases of AML, and the results were compared with those by conventional cytogenetic G-banding (CCG) test.

RESULTSWith multiprobe FISH panel, 22 of the 40 AML cases were found to carry 7 types of cytogenetic abnormalities, namely AML1/ETO transfusion gene, PML-RARα transfusion gene, MLL breakapart, P53 deletion, Del(5q), -7/Del(7q) and trisomy 8. The positive ratio of the multiprobe FISH was 57.5%. CCG only identified 8 cases with the corresponding cytogenetic abnormalities and 3 cases with other cytogenetic abnormalities, and the positive ratio was only 27.50%.

CONCLUSIONMutiprobe FISH panel is more rapid, accurate and effective than CCG in the diagnosis of AML.

Adolescent ; Adult ; Aged ; DNA Probes ; Female ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Leukemia, Myeloid, Acute ; diagnosis ; Male ; Middle Aged ; Young Adult

OBJECTIVETo investigate the cytogenetic differences between children and adults with acute lymphoblastic leukemia (ALL) using eight-probe fluorescence in situ hybridization and karyotype analysis.

METHODSEight-probe (MYC, P16, E2A, TEL/AML1, BCR/ABL , MLL , IGH, and hyperdiploidy) fluorescence in situ hybridization and karyotype analysis were performed for 86 adults and 39 children with acute lymphoblastic leukemia.

RESULTSEight-probe fluorescence in situ hybridization showed significant differences in the positivity rate of TEL/AML1, BCR/ABL, and hyperdiploidy between adult patients and children with ALL. By karyotype analysis, the positivity rate of t(9;22) and hyperdiploidy differed significantly between the children and adult patients (P<0.05).

CONCLUSIONAdults and children with ALL have different expression profiles of the fusion genes. Eight-probe fluorescence in situ hybridization is time-saving, accurate and efficient in detecting common genetic abnormalities in ALL patients, and can be well complementary to karyotype analysis in clinical diagnosis of ALL.

Adolescent ; Adult ; Child ; Child, Preschool ; Cytogenetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Infant ; Karyotype ; Karyotyping ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; genetics ; Young Adult

Objective: To analyze the association of cytogenetic abnormalities with the prognosis of chronic myeloid leukemia (CML) patients in tyrosine kinase inhibitors (TKI) era. Methods: Karyotype analysis of chromosome G-banding was carried out in 387 newly diagnosed CML patients by short-term culture of bone marrow cells. The correlation of cytogenetic abnormalities and CML progression was explored in combination with ABL tyrosine point mutations. Result: Of 387 patients with positive BCR-ABL fusion gene assayed by fluorescence in situ hybridization (FISH) technique, 94.1% (364/387) patients were Ph positive and 5.9% (23/387) Ph negative; 320 patients (87.9%) had a translocation t (9;22) (q34;q11) and 5 (1.4%) a variant translocation t (v;22) . Additional cytogenetic aberrations (ACA) at diagnosis were found in 10.7% (39/387) Ph⁺ patients, major route ACA in 22 (56.4%) cases and minor route ACA in 15 (38.5%) cases and 2 patients (5.1%) lacked the Y chromosome (−Y) ; 23.4% (71/303) patients occurred ACA during TKI treatment and the most frequent abnormalities were abnormal chromosome numbersd, which were likely associated with high proportion of disease progression (χ²=168.21, P<0.001) and ABL tyrosine point mutations (χ²=29.04, P<0.001) . Newly diagnosed CML-CP patients with t (9;22) (q34;q11) had a longer event-free survival (EFS) and disease-free survival (DFS) rates than that of patients with ACA (P=0.037; P=0.003) , while the overall survival (OS) had no significant differences (P=0.209) . As for CML-CP patients that occurred ACA during TKI therapy would have a marked low OS, EFS and DFS (all P<0.001) compared with no ACA occurred patients. Survival of advanced patients that occurred ACA were dramatically reduced. Conclusion ACA often emerged during the disease progress in CML patients, regular and timely detection of chromosomes karyotype and ABL tyrosine point mutations during TKI treatment was important for therapeutic evaluation, progress and prognosis of CML.

Objective: To investigate the clinical implications of p16 gene deletion in adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph⁺ ALL) . Methods: Retrospective analysis of clinical, immunophenotypic, cytogenetics, molecular characteristics and prognosis of 80 newly diagnosed Ph⁺ ALL patients with p16 deletion. Results: Of 80 adult Ph⁺ ALL, the prevalence of p16 gene deletion was 31.3%. p16 gene deletion carriers frequently accompanied with high WBC counts (WBC≥30×10⁹/L) and CD20 expression. The incidence of complex chromosome abnormality in p16 gene deletion group was higher than that in non-deletion group, with alternations in chromosome 7, 8, 19 and der (22) more frequently observed. There was no difference occurred between patients with or without p16 gene deletion in complete remission (CR) rate following induction chemotherapy combined with tyrosine kinase inhibitors (TKIs) . However, after three cycles of chemotherapy, the MMR and CMR rate in the p16 gene deletion group was lower than patients with wild-type p16 gene (P=0.034, P=0.036) . The p16 gene deletion patients showed no significant differences in MMR, CMR and relapse rate between Imatinib or Dasatinib plus chemotherapy (P>0.05) . Deletion of p16 gene was significantly associated with poor outcomes including worse overall survival (OS) (37.1% vs 54.1%, P=0.037) , lower disease free-survival (DFS) (12.4% vs 45.9%, P=0.026) , and increased cumulative incidence of relapse (P=0.033) . Among the 25 patients with p16 deletion, 14 underwent allo-HSCT and the median survival was 21 months, better than that of patients received chemotherapy alone (12 months) (P=0.030) . Conclusion This study indicated that deletion of p16 was associated with poor prognosis in adult Ph⁺ ALL, and the utility of second-generation TKI (Dasatinib) does not necessarily have an edge on efficacy over Imatinib, but allo-HSCT has the potential of elongating life expectancy. It is an important significance to define the status of p16 in Ph⁺ ALL for predicting prognosis and guiding therapy decision-making.

Objective To investigate the correlation between serum levels of prostaglandin-endoperoxide synthase 2(PTGS2),chitinase-3-like protein 1(CHI3L1)and cognitive impairment caused by cerebrovascular disease.Methods From October 2020 to October 2022,96 inpatients with cerebrovascular diseases admitted to the Third People's Hospital of Chengdu were regarded as the study subjects.The basic clinical data of the patients were recorded,the serum levels of PTGS2 and CHI3L1 were detected by enzyme-linked immunosorbent assay,and these patients were grouped into normal group(n=60)and impaired group(n=36)based on the presence or absence of cognitive impairment.The correlation between serum PTGS2 and CHI3L1 levels and fasting blood glucose(FBG)and homocysteine(Hcy)was analyzed by Pearson method.Logistic regression model was used to determine whether serum PTGS2 and CHI3L1 were independent risk factors for predicting cognitive impairment.Receiver operating characteristic(ROC)curve was drawn,and the predictive value of CHI3L1 and serum PTGS2 expression level in cognitive impairment in patients with cerebrovascular disease was analyzed according to the area under the curve(AUC).Results Compared with the normal group,the levels of serum PTGS2(29.30±9.46 pg/ml vs 17.86±5.40 pg/ml)and CHI3L1(13.04±4.06 pg/ml vs 7.51±2.66 pg/ml)in the disorder group were increased,and the differences were statistically significant(t=7.553,8.065,all P＜0.05).Multivariate Logistic regression analysis showed that FBG(OR=3.612,95%CI:2.324～5.614),Hcy(OR=2.584,95%CI:1.351～4.944),PTGS2(OR=1.964,95%CI:1.194～3.231)and CHI3L1(OR= 1.556,95%CI:1.023～2.367)were independent risk factors of cognitive impairment(all P＜0.05).PTGS2 was positively correlated with FBG and Hcy(r=0.368,0.551,all P＜0.05),and CHI3L1 was positively correlated with FBG and Hcy(r=0.510,0.376,all P＜0.05).The ROC curve showed that the area under curve(AUC)of PTGS2 and CHI3L1 in predicting cognitive impairment was 0.819 and 0.829,respectively.The AUC of the combined prediction of cognitive impairment was 0.902,which was obviously higher than that of the independent prediction of the two(Z =2.089,2.293;P=0.037,0.021),with sensitivity and specificity of 77.78%and 98.33%,respectively.Conclusion PTGS2 and CHI3L1 were highly expressed in the serum of patients with cognitive impairment of cerebrovascular disease,indicating that both were related to cognitive impairment of patients with cerebrovascular disease.

OBJECTIVE: The endothelial glycocalyx (eGC) is a dynamic and multicomponent layer of macromolecules found at the surface of vascular endothelium, which is largely underappreciated. It has recently been recognized that eGC is a major regulator of endothelial function and may have therapeutic value in organ injuries. This study aimed to explore the role of the eGC in various pathologic and physiologic conditions, by reviewing the basic research findings pertaining to the detection of the eGC and its clinical significance. We also explored different pharmacologic agents used to protect and rebuild the eGC. DATA SOURCES: An in-depth search was performed in the PubMed database, focusing on research published after 2003 with keywords including eGC, permeability, glycocalyx and injuries, and glycocalyx protection. STUDY SELECTION: Several authoritative reviews and original studies were identified and reviewed to summarize the characteristics of the eGC under physiologic and pathologic conditions as well as the detection and protection of the eGC. RESULTS: The eGC degradation is closely associated with pathophysiologic changes such as vascular permeability, edema formation, mechanotransduction, and clotting cascade, together with neutrophil and platelet adhesion in diverse injury and disease states including inflammation (sepsis and trauma), ischemia-reperfusion injury, shock, hypervolemia, hypertension, hyperglycemia, and high Na as well as diabetes and atherosclerosis. Therapeutic strategies for protecting and rebuilding the eGC should be explored through experimental test and clinical verifications. CONCLUSIONS Disturbance of the eGC usually occurs at early stages of various clinical pathophysiologies which can be partly prevented and reversed by protecting and restoring the eGC. The eGC seems to be a promising diagnostic biomarker and therapeutic target in clinical settings.
Animals ; Databases, Factual ; Endothelium, Vascular ; metabolism ; pathology ; Glycocalyx ; metabolism ; pathology ; Humans ; Shear Strength

OBJECTIVETo investigate and compare the clinical implications of p16 deletion in childhood and adult B-lineage acute lymphoblastic leukemia (B-ALL).

METHODSA total of 129 cases of de novo childhood (73 cases) and adult (56 cases) B-ALL were examined genetically and immunologically using G-banding techniqhe, interphase fluorescence in situ hybridization (I-FISH) and immunophenotyping by flow cytometry, and their clinical data were retrospectively analyzed.

RESULTSOf 73 childhood cases, the prevalences of homozygous deletion, hemizygous deletion and no deletion of p16 were 24.7% (18 cases), 6.8% (5 cases) and 68.5% (50 cases) respectively, and of 56 adult cases, the incidences as of 14.3% (8 cases), 8.9% (5 cases) and 76.8% (43 cases) respectively. The incidence of p16 deletion between the two groups had no significant difference (P = 0.338). In both groups, patients with or without p16 deletion had no significant difference in terms of white blood cells (WBC) count at diagnosis, BM blast percentage, chromosome karyotype, extra-infiltration and CR1 rate. Of note, there were 2 cases, each in childhood and adult, showed no deletion at the time of diagnosis, their p16 deletions occurred at relapse. The deletion of p16 was associated with poor overall survival and event-free survival (EFS) in both childhood and adults. According to the standard of NCI risk stratification, we divided patients of two groups into standard and high risk category respectively, and performed further analysis. The significance of different risk category in children and adults was disparity. The overall survival (OS) rates of deletion and no deletion of p16 were 45.3% and 79.8% (P = 0.006) in children, and 7.7% and 22.6% (P = 0.002) in adults, respectively. EFS rates of deletion and no deletion of p16 were 33.5% and 58.1% (P = 0.008) in children, and 0 and 10.9% (P < 0.01) in adults, respectively. Of the standard risk category in children, OS rates of deletion and no deletion of p16 were 46.8% and 89.3% (P = 0.015) respectively, and EFS rates of deletion and no deletion of p16 as of 40.9% and 82.1% (P = 0.007) respectively. Of the high risk category in children, OS rates of deletion and no deletion of p16 were 41.7% and 67.4% (P = 0.193) respectively, and EFS rates of deletion and no deletion of p16 were 25.0% and 25.6% (P = 0.305) respectively. Of the standard risk category in adults, OS rates of deletion and no deletion of p16 were 20.0% and 46.9% (P = 0.092) respectively, and EFS rates of deletion and no deletion of p16 were 0 and 25.0% (P = 0.062) respectively. Of the high risk category in adults, OS rates of deletion and no deletion of p16 were 0 and 12.4% (P < 0.001) respectively, and EFS rate of deletion and no deletion of p16 was 0 and 4.8%(P < 0.001), respectively.

CONCLUSIONThis study indicated that deletion of p16 was associated with poor prognosis in both childhood and adult B-ALL, which highlighted an important significance to define the status of p16 in both childhood and adult B-ALL for predicting prognosis and guiding clinical intervention.

Adult ; Child ; Female ; Gene Deletion ; Genes, p16 ; Humans ; Male ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; Prognosis ; Retrospective Studies

Objective: To investigate the relationship between plasma level of pro-protein convertase subtilisin kexin type9 (PCSK9) and coronary artery calcification (CAC). Methods: A total of 380 consecutive chest pain patients without lipid-lowering therapy were enrolled. All patients received CT scan and coronary artery calcification (CAC) score measurement and were divided into 2 groups: CAC group, n=156 patients with CAC score>0 and Non-CAC group, n=224 patients with CAC score=0. CAC group was further classified in 3 subgroups as CAC score (1-100) subgroup, n=53, CAC score (101-400) subgroup, n=64 and CAC score>400 subgroup, n=39. Clinical data was collected, plasma levels of PCSK9 were measured in all patients and the relationship between PCSK9 and CAC score was investigated. Results: Plasma PCSK9 level in CAC group was higher than Non-CAC group (260.23±69.34) ng/ml vs (205.46±53.21) ng/ml, P<0.001; alone with CAC score increasing, PCSK9 level was elevating accordingly as in CAC score (1-100) subgroup, CAC score (101-400) subgroup and CAC score>400 subgroup, PCSK9 levels were (247.38±72.68) ng/ml, (264.87±57.63) ng/ml and (295.33±69.06) ng/ml respectively, all P<0.05. With adjusted traditional cardiovascular risk factors, multivariate regression analysis confirmed that plasma PCSK9 level was independently related to CAC score (β=0.584, P=0.002). In addition, the optimal cut-off value for PCSK9 predicting CAC was 228.58 ng/ml with sensitivity at 67% and specificity at 71%. Conclusion: Plasma PCSK9 level was related to CAC in chest pain patients without lipid-lowering therapy.

Objective: To analysis the clinical characteristics and to summarize therapy experience of pediatric patients with cardiac syncope caused by anomalous origin of the left coronary artery from the right sinus (ALCA-R). Methods: We retrospectively analyzed the clinical data including clinical manifestations, myocardial injury biomarkers, radiological features, treatments and prognoses of pediatric patients with ALCA-R who were admitted to Beijing Children's Hospital from November 2015 to June 2018. Results: Four female patients were included in this analysis, age of onset was 7 to 14 years. All the patients presented with exercise-induced syncope and acute myocardial infarction. During the course, three patients presented with acute left heart failure, and one patient had history of sudden cardiac arrest. Laboratory data showed significant elevation of both the creatine kinase and troponin levels in four patients. All electrocardiogram (ECG) showed left main coronary artery occlusion, echocardiography suggested the possible anomalous origin of the left coronary artery in one child. Coronary CT angiography (CTA) revealed there was no coronary ostium in the left coronary sinus, and the left coronary artery had an anomalous origin from the right sinus. The left main coronary artery passed between the ascending artery and the root of the main pulmonary artery, which was compressed by these two large vessels. Two patients underwent cardiac magnetic resonance examination, which detected late gadolinium enhancement in ALCA-R with an interarterial course. Unroofing of the left coronary ostium (cut-back procedure) was performed in two patients, and the other two patients who were not operated were recommended to restrict their physical activities. During a regular follow-up period of 12-43 months, all the children survived without recurrent cardiovascular event. Conclusion: If an adolescent presents with exercise-induced syncope, acute myocardial infarction and even sudden death, and ECG shows left main coronary artery occlusion characteristics, we should consider the possibility of developmental abnormality of coronary artery, particularly the ALCA-R. Once diagnosed as ALCA-R, patients should be recommended to avoid strenuous activities，early recognition and surgical treatment are imperative for these patients.
Adolescent ; Child ; Contrast Media ; Coronary Angiography ; Coronary Vessel Anomalies ; Female ; Gadolinium ; Humans ; Retrospective Studies ; Syncope

Objective: To observe the effect of lipid regulating therapy on carotid atherosclerotic plaque in diabetic patients. Methods: The REACH study, conducted between March 2009 and February 2012, enrolled asymptomatic patients with magnetic resonance imaging (MRI) confirmed carotid atherosclerotic plaque, who had never taken lipid-lowering drugs. Patients were treated with a moderate dose of rosuvastatin for 24 months. Blood lipid levels were measured and carotid MRI was performed at baseline, 3 and 24 months after treatment. The volume of carotid wall and lipid-rich necrotic core (LRNC) were measured by image analysis software. This study retrospectively analyzed patients in the REACH study. Patients were divided into diabetes group and non-diabetic group. The changes of blood lipid level and MRI parameters of carotid atherosclerotic plaque were compared between the two groups and their correlation was analyzed. Results: A total of 38 patients with carotid atherosclerotic plaque were included in this study, including 13 patients (34.2%) in the diabetic group and 25 patients (65.8%) in the non-diabetic group. Baseline parameters were comparable between the two groups, except higher HbA1c level in diabetes group (P<0.05). Compared with baseline, the total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels were significantly decreased at 3 and 24 months in both two groups (P<0.05). The change of high-density lipoprotein cholesterol (HDL-C) in diabetes group was not obvious, while it was significantly increased in non-diabetic group at 24 months ((1.38±0.33) mmol/l vs. (1.26±0.26) mmol/l, P<0.05). MRI results showed that the volume and percentage of LRNC remained unchanged at 3 months, slightly decreased at 24 months (64.86 (45.37, 134.56) mm³ vs. 75.76 (48.20, 115.64) mm³, P>0.05) and (15.84% (11.47%, 24.85%) vs. 16.95% (11.64%, 22.91%), P>0.05) in diabetic group. In non-diabetic group, the volume and percentage of LRNC were significantly decreased at 3 months (63.01 (44.25, 188.64) mm³ vs. 72.49 (51.91, 199.59) mm³, P<0.05) and (13.76% (8.81%, 27.64%) vs. 16.04% (11.18%, 27.05%), P<0.05) respectively. Both parameters further decreased to (55.63 (27.18, 179.40) mm³) and (12.71% (8.39%, 24.41%)) at 24 months (both P<0.05). Wall volume, lumen volume and percent wall volume (PWV) were not affected post therapy in both two groups(P>0.05). There were no correlations between the changes of plaque parameters including volume and percentage of LRNC, wall volume, lumen volume, PWV and the changes of blood lipid parameters (TC, LDL-C, HDL-C and TG) in 3 and 24 months (P>0.05). Conclusion: Lipid-lowering therapy possesses different effects on carotid atherosclerotic plaque in diabetic and non-diabetic patients, and the LRNC improvement is more significant in non-diabetic patients as compared to diabetic patients.
Carotid Arteries/pathology* ; Carotid Artery Diseases/drug therapy* ; Cholesterol, HDL/therapeutic use* ; Cholesterol, LDL ; Diabetes Mellitus ; Humans ; Magnetic Resonance Imaging/methods* ; Necrosis/pathology* ; Plaque, Atherosclerotic/drug therapy* ; Retrospective Studies ; Rosuvastatin Calcium/therapeutic use*