Clinical characteristics and prognosis of 34 cases of acute myeloid leukemia with FLT3 internal tandem duplication and MLL gene rearrangement / 中华血液学杂志

Objective: To analyze the clinical characteristics and prognosis of 34 cases of acute myeloid leukemia (AML) with FLT3 internal tandem duplication (FLT3-ITD) and MLL gene rearrangement. Methods: The clinical data of 34 AML patients with FLT3-ITD and MLL gene rearrangement was compared and analyzed for the therapeutic efficacy, prognostic factors when treated with chemotherapy, chemotherapy combined with targeted therapy or allogenic hematopoietic stem cell transplantation (allo-HSCT). Results: Of the thirty-four cases with median age 41 (4-71) years old, 63.6% presented with white blood cells (WBC) greater than 30×10(9)/L, 39.4% greater than 50 × 10(9)/L respectively on admission. M(5) (35.3%) made up the highest proportion. The cytogenetic abnormality reached 61.8%, of which the complex cytogenetic abnormality accounted for 11.8%. Eleven patients (32.35%) had both FLT3-ITD and MLL gene abnormalities. In addition to FLT3 and MLL abnormalities, 23 patients (67.6%) had one or more other gene abnormalities (multiple gene abnormalities). Of the 34 cases, 29.4% patients went into complete remission (CR) after two courses of chemotherapy. 20.6% (7 patients) went into CR after 3 or more courses of chemotherapy. The rate of early relapse in the CR group was 52.9%. Patients with WBC>50×10(9)/L or multiple gene abnormalities had a lower remission rate (7.7%, 5.4%) after two courses of chemotherapy. CR rate for the patients with more than three gene abnormalities was 0. The total 2-year overall survival (OS) in the 34 patients was 28.8% (95% CI 13.5%-46.0%) and the disease-free survival (DFS) was 27.1% (95% CI 12.5%-44.0%). Of the 18 patients treated with chemotherapy alone or chemotherapy combined with targeted therapy, 17 cases died within 2 years and 1 lost follow-up after giving up treatment. For the 16 patients received allo-HSCT, the 3-year OS was 43.4% (95% CI 13.7%-70.4%) and DFS 42.7% (95% CI 13.4%-69.7%). Conclusion: AML patients with FLT3-ITD and MLL gene rearrangement often presented with M(5), accompanied by hyperleukocytosis, cytogenetic or multiple gene abnormalities. Those patients were observed to have low response rate and high early relapse when treated with chemotherapy without allo-HSCT. Patients had multiple gene abnormalities may be an important poor prognostic factor. Allo-HSCT is an effective treatment which could significantly improve the prognosis and survival of AML patients with FLT3-ITD and MLL gene abnormalities.

Meta-analysis of association of tumor necrosis factor alpha-308 gene promoter polymorphism with gastric cancer / 中华预防医学杂志

<p><b>OBJECTIVE</b>To assess the association between tumor necrosis factor-alpha (TNF-alpha) gene promoter region -308 gene polymorphisms and gastric cancer (GC) susceptibility.</p><p><b>METHODS</b>Published work about TNF-alpha-308 and GC from PubMed, EMBASE, Cochrane library in English and from Wanfang, CBM in Chinese were searched for relevant articles published by the end of July, 2009. Thirty-nine relevant articles were selected and 26 of them met the criteria. The correlated index was extracted for aggregate analysis in RevMan 4.2.</p><p><b>RESULTS</b>There were 5225 GC patients and 8473 controls for TNF-alpha-308 in 26 papers. Overall, allele contrast (G:A and AA:GG) genotype of TNF-alpha-308 polymorphisms produced significant results in worldwide populations, the OR values were 0.85 (95%CI: 0.76 - 0.96, P = 0.01) and 1.19 (95%CI: 1.01 - 1.39, P = 0.03). Subgroup analysis showed that OR values of G:A and AA:GG in west population were 0.79 (95%CI: 0.70 - 0.89, P < 0.01) and 1.26 (95%CI: 1.04 - 1.52, P = 0.02), while in east populations subgroup analysis, the OR was 0.97 (95%CI: 0.75 - 1.26, P = 0.84). No significant association was observed in non-cardia GC and Helicobacter pylori positive GC, the OR values were 0.90 (95%CI: 0.79 - 1.02, P = 0.10) and 1.08 (95%CI: 0.62 - 1.88, P = 0.79).</p><p><b>CONCLUSION</b>TNF-alpha-308 A allele and AA genotype were associated with a statistically significant increased risk of gastric cancer in western people.</p>

An analysis of randomized controlled trials published in the Chinese Journal of Gastrointestinal Surgery between 2003-2009 / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study the academic level of randomized controlled trials (RCT) published in the Chinese Journal of Gastrointestinal Surgery between 2003 and 2009.</p><p><b>METHODS</b>Published RCTs in the 42 issues of the Chinese Journal of Gastrointestinal Surgery was searched for relevant articles published between 2003 and 2009. Data extracted for analysis included the time at manuscript received, publication time, total number of citations, number of citations in Chinese, number of citations in English, author's affiliations, single- or multi- center study, positive conclusions from RCTs, number of patients recruited in RCTs, research funding source, the start time, the finish time and the number of authors in RCTs.</p><p><b>RESULTS</b>During the past seven years, a total of 80 clinical RCTs were published in the Chinese Journal of Gastrointestinal Surgery, accounting for 12% of all the clinical studies published in the journal, and the average number of RCTs in each issue was 1.6. The average delay time before publication was 208 days. The total number of citations and the total number of patients in RCTs were 685 and 9402. The average number of citations, the average number of patients recruited in each RCT, and the average research period in RCTs were 8.6, 118 and 29.2. There were 7 multi-center studies, and the number of single-center study was 73. All the RCT studies had significant conclusions, and 17 (21.3%) RCT studies were funded. Nanjing general hospital of Nanjing military command had the largest number of RCTs (n=6).</p><p><b>CONCLUSION</b>The Chinese Journal of Gastrointestinal Surgery puts emphasis on clinical studies of high evidence level such as RCT, which provide evidence for making the clinical guidelines in the specialty of gastrointestinal surgery.</p>

Induction of rat neural stem cells into oligodendrocyte precursor cells / 生理学报

We have previously established a culture method to isolate and cultivate neural stem cells (NSCs) derived from the rat embryonic brain and spinal cord. In the present study, we demonstrate that the spinal cord-derived NSCs can be induced to differentiate into oligodendrocyte precursor cells (OPCs) with a combined treatment composed of (1) conditioned medium collected from B104 neuroblastoma cells (B104CM) and (2) basic fibroblast growth factor (bFGF, 10 ng/ml). After induction, over 95% of the cells displayed bipolar or tri-polar morphology and expressed A2B5 and platelet derived growth factor receptor-alpha (PDGFR-alpha), markers that are specific for OPCs. Among PDGFR-alpha positive OPCs, only a few cells expressed glia fibrillary acidic protein (GFAP) and none expressed beta-tubulin III. In the presence of B104CM and bFGF, OPCs proliferated rapidly, formed spheres, expanded for multiple passages, and maintained their phenotypic properties. Upon withdrawal of B104CM and bFGF, these cells differentiated into either O4/GlaC-positive oligodendrocytes (OLs) or GFAP- and A2B5-positive type-2 astrocytes. Our results indicate that NSCs can be induced to differentiate into OPCs that possess properties of self-renewal and differentiation into oligodendrocytes and type-2 astrocytes, a property similar to that of O-2A progenitor cells. The OPCs can be maintained in an undifferentiated state over multiple divisions as long as both B104CM and bFGF are present in the medium. Thus, large quantity of OPCs can be obtained through this method for potential therapeutical interventions for various neurological degenerative diseases.

Effects of embryonic neural stem cells and glial cell line-derived neurotrophic factor in the repair of spinal cord injury / 生理学报

The ability of implanted embryonic neural stem cells (NSCs) to improve survival, migration, and functional recovery following a compression spinal cord injury (SCI) was tested in adult rats. NSCs were isolated from E14-16 rat cerebral cortex and SCI was produced by using an aneurysm clip applicator applied to the 8th thoracic spinal cord according to method of Dolan and Tator. Two weeks after the injury, NSCs (4 microl of 1 x 10(4) cells/microl) were injected into the lesion site. The grafted NSCs were noted to survive and integrate with the host spinal cord 1 month after transplantation, which was demonstrated by the presence of Hoechst 33342 (a nuclear dye) pre-labeled NSCs within and surrounding the lesion site. Some of these cells remained undifferentiated and were stained with nestin, a marker for NSCs. Transplanted NSCs migrated for at least 3 mm from the injury epicenter towards both the rostral and caudal directions. Significant reduction in the lesion area (P<0.05) and improvement in inclined plane (P<0.05) and BBB locomotor rating scale (P<0.05) were found in the cases that received implantation of NSCs, as compared with those that received vehicle injection. More importantly, when glial cell line-derived neurotrophic factor (GDNF; 1.5 microg/microl) was added to the transplants, further reduction in lesion area (P<0.01) and improvement in the function were observed in the combined treatment group as compared with the vehicle infused group. Our results suggest that intraspinal treatment with NSCs and GDNF synergistically reduced lesion size and improved functional outcome after a compressive SCI in adult rats.

Isolation and cultivation of neural stem cells from the embryonic rat brain and spinal cord / 生理学报

The aim of this study was to establish the culture system of isolation and cultivation of the neural stem cells (NSCs) from the embryonic rat brain and spinal cord. The methods of microscopic dissection, cell culture and immunofluorescence cytochemistry were used. The results are as follows. (1) In the presence of fibroblast growth factor-2 (FGF-2) and epidermal growth factor (EGF), both brain- and spinal cord-derived stem cells proliferated and expanded in vitro for 8 - 10 passages (over 60 d). The period of expansion resulted in a 10(6)-fold increase in brain-derived NSCs and 10(5)-fold increase in spinal cord-derived NSCs. These proliferating cells expressed nestin. (2) In the medium containing 1% FBS, the two NSCs populations could be induced to differentiate into neurons, astrocytes and oligodentrocytes. The percentage of neurons (beta-tubulin III-ir) differentiated from brain-derived NSCs decreased rapidly from 11.95+/-2.5% at passage 2 (P(2)) to 1.97+/-1.16% at passage 5 (P5). Significant difference was shown between P(2) and P(5) (P<0.01). The percentage of oligodentrocytes (Rip-ir) differentiated from brain-derived NSCs remained mostly unchanged from 8.66+/-2.93% at P(2) to 9.12+/-1.13% at P(5). The same differentiation patterns were found in spinal cord-derived NSCs. All these results indicate that both embryonic rat brain- and spinal cord-derived NSCs can expand and proliferate in vitro through multiple passages, and retain the capacity to differentiate into all three major types of cells in the central nervous system.

Association of HLA-DQB1 coding region with unexplained recurrent spontaneous abortion / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>DNA analysis has shown a lack of significant compatibility between couples affected by unexplained recurrent spontaneous abortion (URSA) compared with normal fertile couples, [8] although one study that made use of a PCR-sequence-specific oligonucleotide (SSO) method did observe evidence of significant compatibility in the HLA-DQA1 and DQB1 alleles between patients and aborted fetuses. [9] This study was designed to investigate whether URSA were associated with particular DQ alleles or promoter alleles.</p><p><b>METHODS</b>Thirty-two patients with URSA and 54 women who had had at least one successful pregnancy were included in this study. HLA-DQ genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The HLA-DQB1 promoter was detected by the SSO and sequence-specific primer (SSP) methods. The DQA1, DQB1, and DQB1 promoter (QBP) gene frequencies in the patients were compared with the gene frequencies in normal controls. The data were analyzed statistically with the chi(2) and Fisher's exact tests.</p><p><b>RESULTS</b>The results showed that the frequency of DQB1 * 0604/0605 was significantly higher and the frequency of DQB1 * 0501/0502 was significantly lower in the patient group as compared with the normal controls. In addition, the frequencies of the DQA1 * 01-DQB1 * 0604/0605 and QBP6.2-DQB1 * 0604/0605 haplotypes were overrepresented in the patients relative to the controls. Our results did not show any differences between URSA patients and the controls with regard to DQA1 and QBP allele frequencies.</p><p><b>CONCLUSIONS</b>Our data suggest that URSA is associated with the HLA-DQB1 coding region, and is not associated with its upstream regulatory region. The DQB1 * 0604/0605, DQA1 * 01-DQB1 * 0604/0605, and QBP6.2-DQB1 * 0604/0605 haplotypes may confer susceptibility to URSA, while the DQB1 * 0501/0502 allele may protect women from URSA.</p>