Establishment of a prediction model for colorectal cancer immune cell infiltration based on the cancer genome atlas (TCGA) database / 北京大学学报(医学版)

OBJECTIVE@#To study the correlation between immune cell infiltration in colorectal cancer tissue and clinical prognosis and to explore the levels of some immune cell genes for predicting the prognosis of patients with glioma colorectal cancer.@*METHODS@#In this study, we extracted colorectal cancer data from the cancer genome atlas (TCGA). Based on a deconvolution algorithm (called CIBERSORT) and clinically annotated expression profiles, the analysis assessed the infiltration patterns of 22 immune cells in colorectal cancer tissue to determine the association between each cell type and survival. Differences in five-year survival rate effectively illustrate the clinical prognostic value of each immune cell proportion in colorectal cancer, using a bar graph, correlation-based heatmap to represent the proportion of immune cells in each colorectal cancer sample.@*RESULTS@#A total of 473 colorectal cancer tissues and 41 normal control tissues were extracted from the TCGA database, and the comparative analysis showed that there were differences in the proportion of various TIICs in colorectal cancer tissues, which could characterize individual differences and have prognostic value. Among the cell subsets studied, the proportions of memory B cells, plasma cells, CD4+ T cells, natural killer (NK) cells, M0 macrophages, M2 macrophages, and activated mast cells were significantly different between normal and cancer tissues. Resting NK cells, CD8+ T cells, and plasma cells were associated with T phase, activated dendritic cells were associated with N phase, and eosinophils, M1 macrophages, and activated mast cells were associated with M phase. Survival analysis showed that activated dendritic cells were positively associated with five-year survival rate in colorectal cancer patients. Naive CD4+ T cells were inversely associated with five-year survival rate.@*CONCLUSION@#There are different degrees of immune cell infiltration in colorectal cancer tissues, and these differences may be important determinants of prognosis and treatment response. We conducted a new gene expression-based study of immune cell subtype levels and prognosis in colorectal cancer, which has potential clinical prognostic value in colorectal cancer patients.

Re-evaluation of classification of myelodysplastic syndromes with low percentage bone marrow blasts / 中华血液学杂志

<p><b>OBJECTIVE</b>To apply the WHO criteria and the minimal diagnostic criteria to the classification of myelodysplastic syndromes (MDS) with low percentage (< 0.050) bone marrow (BM) blasts.</p><p><b>METHODS</b>Two hundred and ten MDS patients with less than 0.050 BM blasts diagnosed between 1988 and 2005 according to FAB criteria were retrospectively reclassified with WHO criteria (2001) and minimal diagnostic criteria.</p><p><b>RESULTS</b>According to the WHO criteria, 5 patients were diagnosed as refractory anemia (RA), 7 as refractory anemia with ringed sideroblasts (RARS), 76 as refractory cytopenia with multilineage dysplasia (RCMD), 9 as RCMD-RS, 35 as MDS-unclassified (MDS-U), 3 as 5q - syndromes, and the rest 75 patients could not be classified suitably. Among the latter 75 patients 16 BM smears showed dysplasia in more than 2 cell lineage but only unilineage cytopenia in peripheral blood (PB). Nine of them were reclassified as RCMD after followed up for more than half a year. Forty-four BM smears showed erythroid dysplasia only, but bicytopenia or pancytopenia in PB. Twenty-seven of them were classified as RCMD after follow-up. Fifteen BM smears not showed dysplasia in any myeloid lineage were reclassified as MDS (5 patients), HS-MDS (5 patients) and idiopathic cytopenia of uncertain significance (ICUS) (5 patients) according to the MDS minimal diagnostic criteria.</p><p><b>CONCLUSION</b>According to WHO criteria (2001), RA is the least diagnosis in MDS. The minimal diagnostic criteria for MDS classification of patients not fulfilled the standard criteria of MDS.</p>

Study on karyotypic abnormalities and its prognostic significance in Chinese patients with primary myelodysplastic syndromes / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the features and prognostic significance of chromosomal karyotype in patients with primary myelodysplastic syndromes (MDS).</p><p><b>METHODS</b>Results of chromosomal karyotypes of 351 adult patients with primary MDS were retrospectively analyzed.</p><p><b>RESULTS</b>Two hundred and thirty-seven cases (67.5%) had karyotypic abnormalities. Of them, 99 (41.7%) were numerical, 70 (29.5%) were structural, and 68 (28.8%) were complex abnormalities. In addition, among the 237 patients with chromosomal abnormalities, 130 (54.8%) showed single abnormality, 54 (22.8%) double abnormalities and 53 (22.4%) complex abnormalities (> or = 3 two independent aberrations). Four cases (1.7%) were multiploid. Aneuploidy or of chromosomal arm anomaly were detected all of the 46 chromosomes and the aberrations in frequent order were +8, -20/20q-, -7/7q-, -5/5q-, -18, -11/11q-/, +21, -Y, -21, -10, -16, -22, +9, del(12)(p12). The incidence of -5/5q- (5.1%) was lower in our series than in western countries (8.7% -23.4%) and 5q- syndrome was even less (0.3%). The incidences of +8 (19.1%) and -20/20q- (9.4%) were higher in our series than in western countries (1.2% -7.0%, 2.0% -3.5%, respectively). Chromosome translocations were detected in 31 cases (13.1%), including 12 novel translocations that have not been reported in MDS patients before. In addition, i(17)(q10) was detected in 9 cases (3.8%) of which 6 were simplex abnormality. Chromosomal duplication presented in 7 cases (3.0%) with 4 cases involved chromosome 1. According to IPSS chromosomal prognostic classification, the incidence of poor-risk karyotypes was increased in the advanced WHO subtypes (P < 0.001). The follow-up data were available in 177 patients with a median follow-up duration of 14.5 (1-131) months. The median OS was 36 [95% confident interval (CI) 25-46] months. According to IPSS chromosomal prognostic classification, the median OS of patients with good, intermediate and poor-risk cytogenetic subgroup were 51 (95% CI 25-77), 35 (95% CI 5-65) and 13 (95% CI 9-17) months, respectively (P = 0.004) and for NN-AN-AA karyotype classification, the median OS of NN, AN and AA were 51 (95% CI 24-78), 36 (95% CI 0.3-71) and 23 (95% CI 10-35) months, respectively (P = 0.039).</p><p><b>CONCLUSION</b>The features of chromosomal abnormalities in Chinese patients with primary MDS shows some difference from that in western countries. Karyotype analysis is of great importance to predict prognosis and to tailor individualized therapy for MDS.</p>

The prognostic value of a modified WPSS based on routine laboratory parameters in patients with myelodysplastic syndromes: a preliminary result / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the prognostic value of a modified WPSS based on routine laboratory parameters in Chinese patients with myelodysplastic syndromes (MDS).</p><p><b>METHODS</b>One hundred and sixty four adult MDS patients were retrospectively analyzed.</p><p><b>RESULTS</b>The median follow-up time was 19 (1-138) months and the median survival (MS) was 36 months. 2-year prospective survival (PS) was 60% and 5-year PS was 42%. In patients with very low-risk, low-risk, intermediate-risk, high-risk and very high-risk stratified by WPSS, 2-year PS was 100%, 96%, 81%, 38% and 14%, and 5-year PS was 100%, 83%, 54%, 20% and 0, respectively (P<0.01). Among parameters of laboratory routine examination, elevated mean cell volume (MCV), mean cell hemoglobin (MCH), neutrophil alkaline phosphatase (N-ALP) index and nucleated RBC PAS negative were good prognostic factors, while reduced Hb, BPC and bone marrow elevated blasts, dysplasia more than 1 lineage, and lymphocyte-like micromegakaryocyte (MEGly) as well as elevated serum LDH were poor prognostic factors in uni-variable analysis. Among them, MCV, MEGly and blast had independent prognostic significance in multi-variable analysis (P = 0.011, 0.013 and 0.016, respectively). WPSS was modified by omitting chromosomal karyotype and transfusion dependence and adding MCV and MEGly. In patients with low-risk, intermediate-risk and high-risk stratified by modified WPSS, 2-year PS was 94%, 68% and 49%, respectively; and 5-year PS was 86%, 53% and 14%, respectively (P<0.01).</p><p><b>CONCLUSION</b>The modified WPSS worked well for prognostic prediction in Chinese patients with MDS.</p>

Studying of clinical and laboratory features of chronic eosinophilic leukemias /hypereosinophilic syndrome / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical and laboratory features of chronic eosinophilic leukemias (CEL) and hypereosinophilic syndrome (HES).</p><p><b>METHODS</b>The clinical manifestations, laboratory parameters were retrospectively analyzed in 20 patients with HES/CEL. Detection of the FIP1L1-PDGFRA fusion gene was performed by nested RT-PCR. JAK2 V617F mutation screening was processed through allele-specific PCR combined with sequence analysis. PCR-RFLP was used to discriminate homozygous from heterozygous mutation patterns. TCR gamma rearrangement was detected by PCR.</p><p><b>RESULTS</b>Of the 20 patients, 19 were males and one female, with a median age of 33 (20 to 57) years. The FIP1L1-PDGFRA fusion gene positivity in bone marrow mononuclear cells in 12 cases was identified. All the breakpoints were identified by direct sequencing of cloned RT-PCR products in FIP1L1 intron 10 - 12 and in PDGFRA exon 12. In CEL the most common involved organs were lungs, heart and nervous system. Splenomegaly was significantly more frequent in CEL than in HES (92.5% vs 42.5%, P = 0.031). Anemia and myelofibrosis were common in CEL. There was no significant difference in circulating absolute eosinophil, leukocyte, platelet counts, hemoglobin level and percentages of eosinophil and blast cell in bone marrow between CEL and HES. The morphological abnormalities of eosinophils on bone marrow smear were easily found in CEL, including hypogranularity, and cytoplasmic vacuolization, increased basophilic granule. One patient with HES was found to have heterozygous JAK2 V617F mutation. Six patients had TCR gamma rearrangement, including 4 CEL and 2 HES.</p><p><b>CONCLUSIONS</b>(1) There is a male predominance in HES/CEL, and the median age was in the thirties. (2) The most common involved organs in CEL were lung, heart and nervous system. Bone marrow morphology might be of a little help in diagnosis of CEL. (3) JAK2 V617F may be involved in the pathogenesis of HES. (4) Patients with CEL carried the FIP1L1-PDGFRA fusion gene and TCR gamma rearrangement concurrently, their relationship warrants further study.</p>

Preliminary study of diagnosis of patients with myelodysplastic syndromes by routine laboratory parameters / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the value of routine laboratory parameters in diagnosis of myelodysplastic syndromes (MDS) and differential diagnosis of patients with hypoplastic MDS from chronic aplastic anemia (CAA) for providing reference standard for primary hospitals.</p><p><b>METHODS</b>The laboratory parameters at diagnosis of 152 MDS patients with less than 0.05 bone marrow blasts and 86 CAA patients were retrospectively analyzed.</p><p><b>RESULTS</b>There were significant differences between MDS and CAA in Hb, red cell distribution width-coefficient variation (RDW-CV), immature reticulocyte fraction (IRF), BPC, the ratio of G1 (the sum percentage of myeloblast and promyelocyte) to G2 (the sum percentage of neutrophilic myelocyte and metamyelocyte) (Ratio G), the ratio of El (the sum percentage of proerythroblast and early erythroblast) to E2 (the sum percentage of intermediate erythroblast and late erythroblast) (Ratio E), megakaryocyte count (Meg), erythroblast PAS, neutrophil alkaline phosphatase (N-ALP), and serous levels of indirect bilirubin (IBIL), lactose dehydrogenase (LDH), folic acid (FA), VitB12 and ferritin. Chromosome abnormalities were found in 74 MDS patients (48.7%) but in none of CAA patients (P < 0.001). Furthermore, for differentiating MDS with less than 0.05 blasts from CAA, the sensitivity and specificity of combination of Meg, PAS, and IBIL level was 89.1% and 92.7%, the Youden index (gamma) was 0.818. Moreover, in the seven hypoplastic MDS cases, BPC, myeloblast percentage, Ratio G, Meg, erythroblast PAS and FA were statistically different from those of CAA; the sensitivity and specificity of combination of PAS and BPC was 85.7% and 100%, the gamma was 0.857; the sensitivity and specificity combination of Ratio G, Meg PAS was 85.7% and 98.8% respectively, the gamma was 0.845.</p><p><b>CONCLUSION</b>The routine laboratory parameters, especially BPC, Meg, Ratio G, PAS, IBIL may be helpful for the diagnosis of MDS and differential diagnosis of hypoplastic MDS from CAA.</p>

Effects of Coincident Infection on Treatment Response and Coronary Artery Lesion Outcome in Children with Kawasaki Disease / 实用儿科临床杂志

Objective To explore the effects of coincident infection on treatment response and coronary artery lesion (CAL) outcome in children with Kawasaki disease(KD).Methods A retrospective study of 141 children diagnosed on KD between Jul.2005 and Dec.2006 were performed.Standardized clinical assessments,laboratory examinations microbiology test results plus treatment regimens were reviewed.CAL were visualized by using echocardiography.Infectious agents positive (INF+) and negative (INF-) groups were identified,and clinical assessments,laboratory and treatment data were analyzed.Results 1.Concurrent infections:41%(58/141) of children had one of above confirmed infection at KD diagnosis.2.Treatment response:the presence of infection did not alter the response to treatment with intravenous immunoglobulin (IVIG),with resolution of fever within 72 h in 85% (120/141) children after 1 dose of IVIG (2 g/kg) together with aspirin administration regardless of present or absent infection.3.CAL outcome:in total,56.0% (79/141) of children developed CAL at the time of diagnosis,involving dilatation (91.1%,72/79 cases) and aneurysm (8.9%,7/79 cases),and no giant aneurysm was found.Most CAL were recovered within 1 year after treatment.Incidence of aneurysm in INF+ group was significantly higher than that in INF-group (P=0.019).Conclusions Coincident infection would not affect on the clinical assessment,laboratory test results and treatment response to IVIG in children with KD,but would result in higher risk of serious CAL.Therefore,children with infection at diagnosis on KD will not only accept active treatment in acute phase,but also insist on convalescent care and follow-up visit.

Karyotypic and IPSS grouping of primary myelodysplastic syndromes patients: a comparison between FAB- and WHO-classification / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the results of cytogenetic and IPSS grouping of primary myelodysplastic syndromes (pMDS) patients classified by FAB- or WHO classification.</p><p><b>METHODS</b>Two hundred and thirty seven cases of pMDS who were previously classified according to FAB criteria were reclassified with WHO classification. A comparison was made between the results of the two classifications.</p><p><b>RESULTS</b>For the detection rates of cytogenetic abnormality and its risks group, there was no difference among the FAB subgroups but the detection rate was different between the WHO refractory cytopenia with multilineage dysplasia (RCMD) and RA subgroups (74.4% and 42.5%, respectively) (P < 0.001). The percentage of good karyotype abnormalities in RA (65.0%) was higher than that in RCMD (24.4%) (P < 0.001), and the percentages of intermediate and poor karyotype abnormalities in RCMD (48.9% and 26.7%, respectively) were higher than that in RA (27.5% and 7.5%, respectively) (P < 0.05). There was a good correlation between the subgroups and IPSS risk groups for both the WHO classification and the FAB classification, but the WHO classification further reflected the differences between RCMD and RA and RAEB-I and RAEB-II subgroups. The percentage of low-risk group in RCMD (1.1%) was lower than that in RA (10.0%) (P < 0.05), and the percentage of high-risk group in RAEB-II (30.5%) was higher than that in RAEB-I(0) (P < 0.001).</p><p><b>CONCLUSION</b>For the correlation between subgroups and cytogenetic abnormalities and IPSS risk groups, the WHO-classification is better than the FAB-classification.</p>

Morphologic and clinical study of 131 cases of plasma cell myeloma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the characteristics histologic and cytologic features and clinical usefulness of plasma cell myeloma (PCM) subtyping according to WHO PCM classification.</p><p><b>METHODS</b>Bone marrow biopsy plastic-embedded sections were stained with H-G-E and Gomori's stains, and bone marrow aspirate smears were stained with Wright's stain. The clinicopathologic findings were then analyzed.</p><p><b>RESULTS</b>Of the 131 cases with PCM, three types of growth patterns were noted: interstitial (21 cases, 16.0%), nodular (46 cases, 35.1%) and packed (64 cases, 48.9%). Besides, there were three cytologic subtypes: mature plasma cell type (43 cases, 32.8%), immature (81 cases, 61.8%) and pleomorphic (7 cases, 5.3%) types. The age of patients with mature plasma cell type was significantly higher than that of immature type (P = 0.005); and the number of tumour cells in bone marrow smears was significantly higher than that of immature type (P = 0.003). The numbers of WBC and platelets in peripheral blood were also significantly higher than that of pleomorphic type (P = 0.024, P = 0.002, respectively). On the other hand, the number of platelets in peripheral blood of immature type was significantly higher than that of pleomorphic type (P = 0.019). Marrow fibrosis was more frequently observed in immature type than in mature plasma cell type (P = 0.000). The incidence of marrow fibrosis and osteolytic lesions was higher in high risk group than in low risk group (P = 0.000, P = 0.023 respectively). Twenty-one cases (56.8%) of the 37 cases treated with MP or MP and M2 chemotherapeutic regimens showed good response. However, there was no significant difference in treatment response and survival between different subtypes.</p><p><b>CONCLUSIONS</b>Each subtype of PCM carries different clinicopathologic features in some aspects. The classification carries important value in pathologic diagnosis and probably in predicting prognosis.</p>

Clinical characteristics and prognosis of 33 children with severe acute respiratory syndrome in Guangzhou area / 中华儿科杂志

<p><b>OBJECTIVE</b>Since the outbreak of a highly contagious new pneumonia, atypical pneumonia or severe acute respiratory syndrome (SARS) occurred in Guangzhou area, 33 children with this syndrome were treated in the authors' hospital. The present study aimed to understand clinical characteristics and prognosis of pediatric SARS patients in Guangzhou area.</p><p><b>METHODS</b>Clinical manifestations, laboratory and radiologic findings, therapeutic approaches and prognosis of the 33 children with SARS in Guangzhou area were analyzed.</p><p><b>RESULTS</b>Of the 33 cases, 17 were males and 16 were females. The age was between 3 months to 13 years, and 3 - 12 years old patients accounted for 82%. Five (15%) cases had an evident history of contacting SARS patient before the symptoms occurred. Another 5 (15%) cases had a history that contacts of these patients (family members or friends) developed fever and/or cough later. The most common symptoms in this cohort were fever (100%) and cough (91%). Most of the cases had high fever, higher than 39 degrees C. Near half of the cases had nonproductive cough. The initial blood cells count showed that total white blood cell (WBC) count was (2.5 - 9.7) x 10(9)/L. In 22 (67%) cases the WBC count was < 5.0 x 10(9)/L, and in 10 (30%) WBC was (5.0 - 7.0) x 10(9)/L, in 18 cases most of the WBC were lymphocyte count. Chest radiograph showed patchy infiltrates, in 15 cases the changes were unilateral, and in 18 were bilateral. The radiologic changes developed fast, in some cases the changes progressed from one side to both sides. The opacity was absorbed slowly, significant absorption took in average two weeks. Elevated ALT was found in 3 cases and elevated CK-MB in 2 cases. Treatment included isolation, good ventilation of the ward, bed rest, supportive regimens, low volume oxygen inhalation, use of Chinese traditional medicine, antibiotics to prevent bacterial infection, and anti-inflammation therapy. All the patients recovered and discharged from hospital after a mean period of 10.0 +/- 3.8 days.</p><p><b>CONCLUSION</b>SARS in children may have its own characteristics. The main clinical manifestations were high fever and cough while no severe toxic symptoms, nor respiratory failure was seen; few symptoms or signs suggesting involvement of systems other than respiratory system were seen. Chest radiograph showed uni- or bilateral asymmetric air-space infiltrates which could worsen quickly and were absorbed slowly. Though there were severe changes in the lung, the patients might not have corresponding symptoms or signs. The total white blood cell count in peripheral blood did not increase. All the patients studied had a favorable outcome after the combined treatment.</p>

Effect of Dipyridamole Therapy on Kawasaki Disease with Glucose-6-Phosphate Dehydrogenase Deficiency in Children / 实用儿科临床杂志

Objective To evaluate the therapy and turnover of Kawasaki disease(KD)with glucose-6-phosphate dehydrogenase(G-6-PD)deficiency.Methods Six hundred and twenty-four patients with KD were selected including 32 patients who had G-6-PD defected.The same dose intravenous immunoglobulin(IVIG)was used in all 624 patients(2 g/kg),but used Dipyridamole in 32 patients had G-6-PD deficiency which replaced the role of acetylsalicylic acid(ASA)after acute period.The coronary artery of these patients were checked and followed-up through echocardiograph.The turnover of 32 patients with G-6-PD deficiency and 356 case selected randomly from all the KD patients were compared.SPSS 10.0 software was used to analyze the data.Results In 32 cases of KD with G-6-PD deficiency,4 children had coronary aneurysm(12.5%).After 6-12 months follow-up,the coronary lesions were recovered in 62.5% children,improved in 21.9% children and not improved in 15.6% childern,which were not significantly different from all the KD patients(Z=-1.604 P=1.09).Conclusions IVIG and Dipyridamole are feasible in treating KD with G-6-PD deficiency.J Appl Clin Pediatr,2009,24(1):26-27