Clinical Significance of Common Gene Mutations in 53 Patients with Acute Myeloid Leukemia Harboring 11q23/MLL Rearrangements / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical significance of AML patients with 11q23/MLL rearrangement, and to evaluate the effect of those mutations on the AML patients.@*METHODS@#53 cases involving translocations of chromosome 11q23 were identified by chromosome banding analysis. MLL rearrangements were detected by fluorescence in situ hybridization and/or multiplex nested PCR. The samples were screened for mutations in the candidate genes FLT3-ITD, FLT3-TKD, TET2, N-RAS, ASXLI, EZH2, DNMT3, C-Kit, NPM1, WT1, CEBPA by using genomic DNA-PCR and deep-sequencing.@*RESULTS@#21/53 MLL-rearranged AML cases showed at least one additional chromosomal aberrations. The most common additional aberration was +8. Gene mutations were observed in 23 cases (43.4%) and most cases showed singal mutation. N-RAS mutation was more frequent (8 cases, 15.1%), followed by WT1 mutation in 4 cases (7.5%), FLT3-ITD mutation in 3 cases, ASXL1 mutation in 2 cases, DNMT3A mutation in 2 cases, EZH2 mutation in 1 case, c-Kit17 mutation in 1 case, FLT3-TKD mutation in 1 case, and FLT3-ITD and TKD mutation coexistent in 1 case. No mutation was detected in CEBPA, NPM1, C-KIT8, TET2. Median OS for gene mutated patients was 8.5 months and 13 months for no mutated patients. Median OS for patients who received hematopoietic stem cell transplantation (HSCT) was 22.5 months and 7.5 months for patients who olny received chemotherapy.@*CONCLUSION@#A relatively high mutation frequency is observed in AML patients with 11q23/MLL rearrangements and most cases shows single mutation. The RAS signaling pathway alterations are most common. Gene mutation does not affect the OS of these patients, who show poor prognosis. A significantly higher Hb at initial diagnosis in FLT3 mutated patients is significantly higher than that in FLT3 wild-type cases. Patients who underwent HSCT show a better prognosis than those only received chemotherapy.

Effect of Chinese medicine of nourishing kidney and clearing liver on intermittent hypoxia induced injury model of HUVECs through p38MAPK/NF-κB signaling pathway / 中国中药杂志

This study aims to explore the intervention effect of Chinese medicine of nourishing kidney and clearing liver on intermittent hypoxia(IH) induced injury model of HUVECs through p38MAPK/NF-κB signaling pathway in vitro. HUVECs injury model was induced by modified IH treatment. The effective components of Chinese medicine of nourishing kidney and clearing liver including isochteroside, aucubin and ligustrazine were used as intervention drugs. The optimal compatibility concentration of them was screened in vitro, and then the optimal compatibility concentration was selected as the intervention dose to observe the effect on p38MAPK/NF-κB signaling pathway in IH induced injury model of HUVECs. The results showed that isochnae, aucubin and ligustrazine had the best anti-inflammatory effect at concentration of 0.01 mg•L-1. NF-κB p65 and p-IκB in the nucleus in IH group were significantly higher than those in the normal control(N) group and the other groups. Immunofluorescence staining showed significant translocation of NF-κB p65 nucleus in IH group, and HUVECs adhesion capacity in IH group was increased significantly. As compared with IH group, the expression levels of p-p38MAPK, NF-κB p65 and p-IκB in p38MAPK inhibitor(INH) group and Chinese medicine of nourishing kidney and clearing liver(GDC) group were significantly decreased, and HUVECs adhesion capacity in INH group and GDC group was significantly inhibited as well. The optimal concentration of Chinese medicine of nourishing kidney and clearing liver can inhibit the phosphorylation of p38MAPK, and then inhibit the nuclear translocation and transcription function of NF-κB. This may be the mechanism of the protective effect of Chinese medicine on IH induced injury model of HUVECs.

Community colorectal cancer screening program in Shanghai / 上海预防医学

Shanghai public health service-community colorectal cancer screening program, was officially launched in November 2012 , so as to carry out colorectal cancer prevention and health education through free screening services in the whole city.The establishment of the program was based on the comprehensive analysis of disease burden caused by colorectal cancer in Shanghai, with three years of pilot study in Qibao Community.In the first round of screening, one million people participated and 1 960 colorectal cancer cases were detected, with the proportion of the earlier stage cancer being 52.8%, which was 4.36 times the level in Shanghai before screening.At the same time, 7 911 cases of precancerous lesion were detected.The objective of program was achieved, with precious experience obtained in implementation of similar disease screening programs.

Correlation between expression of SIL-TAL1 fusion gene and deletion of 6q in T-cell acute lymphoblastic leukemia / 中国实验血液学杂志

The present study was designed to investigate the prevalence and clinical significance of SIL-TAL1 rearrangements in T-cell acute lymphoblastic leukemia (T-ALL). The incidence of SIL-TAL1 rearrangements was analyzed by nest real-time quantitative polymerase chain reaction (RT-PCR) in 68 patients with T-ALL. Karyotypic analysis was performed by conventional R-banding assay and array-based comparative genomic hybridization (array-CGH). The results showed that SIL-TAL1 rearrangements were identified in 10/26 (38.5%) pediatric and 2/42 (4.8%) adult T-ALL cases, which indicate a pediatric preference for SIL-TAL1 rearrangements in T-ALL. Two different transcripts were detected in 6/12(50%) T-ALL samples. Abnormal karyotypes were detected in 6 out of 11 cases (54.5%) and a deletion of the long arm of chromosome 6 was observed in 4 cases. Array-CGH results of 2 T-ALL cases with SIL-TAL1 rearrangement revealed that this fusion gene was resulted from a cryptic deletion of 1p32, and the overlap region of 6q deletion was 6q14.1-16.3. These cases with SIL-TAL1 fusion had a higher white blood cell (WBC) count and higher serum levels of lactate dehydrogenase (LDH) than cases without SIL-TAL1 fusion. It is concluded that SIL-TAL1 rearrangements are associated with loss of heterozygosity of chromosomal 6q, and SIL-TAL1-positive patients are younger than SIL-TAL1-negative patients. In contrast to the cases without SIL-TAL1 fusion, there are many adverse prognostic factors in the cases with SIL-TAL1 fusion, such as higher WBC count and higher LDH levels.

Recent incidences and trends of childhood malignant solid tumors in Shanghai, 2002-2010 / 中华儿科杂志

<p><b>OBJECTIVE</b>To examine the recent incidences and trends of childhood malignant solid tumors in Shanghai.</p><p><b>METHOD</b>Data from the population-based Shanghai Cancer Registry and related retrospective survey were used to analyze the patterns of incidence and trends of malignant solid tumors diagnosed between 2002 and 2010 in children aged 0-14 years. The distributions of incidences were described according to gender, age and cancer types which were classified according to International Classification of Childhood Cancer (ICCC). Annual age-standardized rates (ASRs) were adjusted by the world standard population. Approximate confidence intervals for standardized rate ratios (SRR) based Poisson distribution test-based methods were used to assess changes in incidence over the period 2002 - 2006 and 2007 - 2010.</p><p><b>RESULT</b>(1)A total of 868 cases of childhood malignant solid tumors were diagnosed in Shanghai during 2002 - 2010, accounting for 65.8% of all childhood cancers. The ASR of 2002 - 2010 was 80.2 per million for all solid tumors. (2) The ASR was higher in boys (86.3 per million) than in girls (73.8 per million) with SRR 1.2 (95%CI 1.0 - 1.3). Incidence rate was the highest in the first five years of life with 93.4 per million. The age-specific incidence rates in 5 - 9 and 10 - 14 age groups were 65.2 and 79.3 per million, respectively. (3) CNS tumors, lymphomas, germ cell tumors, neuroblastoma, and soft tissue sarcomas were the top 5 most common solid tumors in children, with the incidence rate of 23.8, 11.0, 7.8, 7.7 and 6.8 per million, respectively. The patterns of subgroups varied in different age groups. Blastomas, such as neuroblastoma, retinoblastoma, were more common in the children aged 0 - 4 years, whereas epithelial carcinomas and bone tumors developed more frequently in elder children aged 10 - 14 years. (4) Compared with the ASR in 2002 - 2006, the ASR for both genders in 2007 - 2010 had no substantial changes (78.7 per million in 2002 - 2006 and 82.9 per million in 2007 - 2010). However, among boys, the incidence rate in 2007 - 2010 was significantly higher than that in 2002 - 2006 with SRR 1.2 (95%CI: 1.0 - 1.4). For specific subgroups of cancer, there were no substantial changes. Some cautions should be taken when interpreting results involving a small number of cases per year and those with wide 95% confidence intervals.</p><p><b>CONCLUSION</b>The incidence rate of pediatric malignant solid tumors among males was higher than females during 2002 - 2010, and it differed among different age groups with the highest in the first five years of life. CNS tumor was the most common type of solid tumors in children. This was a unique characteristics comparing with adult reflected in disease spectrum and age of onset. The patterns of incidence and its trends for childhood malignant solid tumors in Shanghai could provide a basis for etiologic research and preventive interventions. The findings also suggest an urgent need for longer population-based surveillance to verify the pattern and changing trends.</p>

Chronic intermittent hypoxia and hypertension: a review of systemic inflammation and Chinese medicine / 中国结合医学杂志

Obstructive sleep apnea syndrome (OSAS) and hypertension commonly coexist. Clinical studies indicate that OSAS plays a key role in increasing the risk of prevalent hypertension. Chronic intermittent hypoxia (CIH) is the core pathological mechanism of OSAS, and has a close relationship with systemic inflammation. Growing evidence shows that CIH and hypertension are strongly related, involving markers or pathways indicative of systemic inflammation, such as high-sensitivity C-reactive protein (hs-CRP), interleukin-6, nuclear factor-kappa B, tumor necrosis factor-α, interleukin-8 and p38 mitogen-activated protein kinase (MAPK)-dependent pathways. Oxidative stress also plays an important role in this process, including in the activation of polymorphonuclear neutrophils. However, the pathophysiological and clinical significance of systemic inflammation in CIH and hypertension is not proven. This review article highlights the relationship between CIH and hypertension through systemic inflammation and the current interventions available in Chinese medicine, to offer a background for the future treatment of OSAS-related hypertension with integrative medicine.

Clinical and cytogenetic study of 6 cases of hematological disorders associated with 20q- and t (20;21) (q11;q11) abnormalities / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze clinical and cytogenetic features of hematological disorders associated with 20q- and t (20;21) (q11;q11) abnormalities.</p><p><b>METHODS</b>Following short-term culture of bone marrow cells, karyotypic analysis was carried out with R-banding. 20q- and t(20;21) (q11;q11) was detected by fluorescence in situ hybridization (FISH) using dual-color 20q11/12 probe, ST 20qter /ST 21qter probes, SE20(D20Z1)/SE 13/21 probes, and WC20/WC21 probes.</p><p><b>RESULTS</b>Six (2.3%) of the 257 patients with 20q- detected by conventional karyotypic analysis were found to have t(20;21) (q11;q11) abnormality. Five cases had myelodysplastic syndrome, 1 had acute lymphoblastic leukemia. Above results were all confirmed by FISH.</p><p><b>CONCLUSION</b>i (20q-), t(20;21) (q11;q11) seems to be a rare but recurrent chromosomal abnormality which is specifically associated with myeloid disease, late occurrence and poor prognosis. The translocation between chromosome 20q11 and 21q11 may form a novel fusion gene which has an important role in the pathogenesis of the disease.</p>

Expression of SET-NUP214 fusion gene in patients with T-cell acute lymphoblastic leukemia and its clinical significance / 中国实验血液学杂志

This study was aimed to investigate the occurrence and clinical significance of the SET-NUP214 fusion gene in patients with T-cell acute lymphoblastic leukemia (T-ALL), analyse clinical and biological characteristics in this disease. RT-PCR was used to detect the expression of SET-NUP214 fusion gene in 58 T-ALL cases. Interphase FISH and Array-CGH were used to detect the deletion of 9q34. Direct sequencing was applied to detect mutations of PHF6 and NOTCH1. The results showed that 6 out of 58 T-ALL cases (10.3%) were detected to have the SET-NUP214 fusion gene by RT-PCR. Besides T-lineage antigens, expression of CD13 and(or) CD33 were detected in all the 6 cases. Deletions of 9q34 were detected in 4 out of the 6 patients by FISH. Array-CGH results of 3 SET-NUP214 positive T-ALL patients confirmed that this fusion gene was resulted from a cryptic deletion of 9q34.11q34.13. PHF6 and NOTCH1 gene mutations were found in 4 and 5 out of 6 SET-NUP214 positive T-ALL patients, respectively. It is concluded that SET-NUP214 fusion gene is often resulted from del(9)(q34). PHF6 and NOTCH1 mutations may be potential leukemogenic event in SET-NUP214 fusion gene.

Status and trends of breast cancer mortality in Chinese females / 中华预防医学杂志

<p><b>OBJECTIVE</b>To describe the current status of mortality breast cancer in Chinese females between 2004 and 2005, as well as its developing trend from 1973 to 2005.</p><p><b>METHODS</b>The data of female breast cancer deaths and number of female under exposure were collected through the Third National Mortality Retrospective Sampling Survey, which covered a total of 69 690 241 person years of females. The data was descriptively analyzed, and compared with the data of time-trend of breast cancer mortality in the previous two surveys in 1973 - 1975 and 1990 - 1992 respectively.</p><p><b>RESULTS</b>The crude mortality of female breast cancer in China in 2004 - 2005 was 5.90 per 100 000 (4112/69 690 241), ranking the sixth most common cancer death in Chinese females, and accounted for 5.90% (4112/69 667) of all female deaths from cancer. The crude mortality of female breast cancer was 6.86/100 000 (1777/25 900 856) in the eastern China, 5.91/100 000 (1431/24 225 738) in the central China and 4.62/100 000 (904/19 563 647) in the western China. The age-standardized mortality among Chinese standard population of female breast cancer in urban area (4.91/100 000, 1899 death cases) was 1.44 times higher than that in rural area (3.42/100 000, 2213 death cases). The crude mortality increased 99.99% from 1973 - 1975 (2.95/100 000) to 2004 - 2005 (5.90/100 000), the absolute figure increased by 2.95/100 000. The age-standardized mortality among Chinese standard population increased 37.85% from 1973 - 2005 (2.88/100 000) to 2004 - 2005 (3.97/100 000), the absolute figure increased 1.09/100 000.</p><p><b>CONCLUSION</b>The mortality of female breast cancer in urban area was higher than that in rural area, and it decreased from the eastern China, to the central China and to the western China in turn. The mortality of female breast cancer has constantly increased in China since 1973.</p>

Time trends and characteristics of gastric cancer incidence in urban Shanghai / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the time trends during 1973 - 2004 and the current characteristics of gastric cancer incidence in Shanghai and to develop strategies for control and prevention.</p><p><b>METHODS</b>All data from the Malignant Cancer Registry System of Shanghai were retrieved and time trends of male and female incidence rates for gastric cancer in urban population from 1973 to 2004 were assessed by annual percentage change (APC) of the crude rates and age-adjusted rates. The APC was calculated by fitting a least squares regression line to the natural logarithm of the rates, using the calendar year as a regressor variable. Based on the computerized data from 2002 to 2004, the current characteristics of urban gastric cancer incidence were analyzed regarding sex, age, stage at diagonsis, histopathologic type and location of the tumor (s). The number and structure of population were obtained from Shanghai Municipal Public Security Bureau. The incidence rates were standardized under the world population. The constituent ratios were analyzed by Chi-square test. Statistical analyses were performed with the SPSS software package for Windows, version 10.0.</p><p><b>RESULTS</b>Substantially and continuously decreasing trends were noticed in gastric cancer incidence during the past 32 years in urban Shanghai, both in males and in females. The age-standardized rates (ASR) dropped 54.4% in males and 37.6% in females. From 2002 to 2004, 7630 new cases of gastric cancer were registered in urban Shanghai with the ASRs of male and female gastric cancer as 27.4 and 14.0 per 100 000. Under the age of 40, the age-specific incidence was quite low that no differences were found between men and women. However, the incidence increased significantly after age of 40 and differences of increase were shown between the two sexes. About 46.1% of all the cases had detailed records of TNM stage, in which IV stage was the majority while I stage the least. About 74.1% of all the cases were diagnosed histopathologically and 71.7% of all had detailed records on histopathologic types. Adenocarcinoma was the most common type (76.8%), followed by signet ring cell carcinoma (9.4%). The proportions of adenocarcinoma and tubular adenocarcinoma were higher in males than in females while signet ring cell cancer was higher in females than in males. Intestinal type gastric cancer was the most prominent type in Lauren system. The proportion of male was higher than female in intestinal type whereas female was higher than male in diffused type. In lesion location, the antrum was the most common tumor site. The gastric antrum cancer of females was more common than males while the gastric cardia cancer presented quite the contrary. The proximal gastric cancer was more prevalent in males than in females whereas the distal gastric cancer was in opposite pattern.</p><p><b>CONCLUSION</b>A dramatic decreasing trend during 1973 - 2004 and several current and interesting characteristics in view of gender, age, stage at diagnosis, histopathologic type and tumor location of gastric cancer in urban Shanghai were determined in this study, which might contribute to the development of control and prevention strategy for gastric cancer.</p>

Study on the prevalence of depression among cancer patients and its influencing factors in Shanghai / 中华流行病学杂志

<p><b>OBJECTIVE</b>To determine the prevalence of depression among cancer patients and its influencing factors.</p><p><b>METHODS</b>We investigated 7967 cancer patients who lived in communities with cluster sampling based on 'Shanghai Cancer Patient Database'. They were investigated through questionnaires and completed the Zung Self-rating Scale. 6694 questionnaires were identified as 'qualified'. We calculated the prevalence of depression and determined the factors with logistic regression model.</p><p><b>RESULTS</b>The prevalence rate of depression among cancer patients in communities was 24.74% (95% CI: 23.71% - 25.79%). Results from multi-factor analysis showed that duration since diagnosis, stages at diagnosis, metastasis, therapeutics, KPS scores, and pain VAS scores were the important factors.</p><p><b>CONCLUSION</b>Early detection, improving the curative effect and providing community health services could reduce the prevalence of depression.</p>