[CD7 expression and its prognostic significance in acute myeloid leukemia patients with wild-type or mutant CEBPA].

Objective: To analyze the prognostic value of CD7 expression in newly diagnosed acute myeloid leukemia (AML) patients, and to further explore the correlation between CD7 expression and CEBPA mutation, and to clarify the prognostic value of CD7(+) in AML patients with wild-type (WT) or mutant-type (MT) CEBPA. Methods: The clinical data of 298 newly diagnosed non-M(3) AML patients between January 2010 and December 2016 were analyzed retrospectively. The clinical characteristics and prognosis of CD7(+) and CD7(-) patients were respectively compared in all patients, and in patients with WT and MT CEBPA. The relationship between CD7 expression and CEBPA mutation was determined by chi-square, and the effects of CEBPA mutation on survival and prognosis in CD7(+) group by Kaplan-Meier method. Results: In CD7(+) group, the frequencies of CEBPA mutation were 10.1% (single site) and 33.9% (double site) , significantly higher than those of the CD7(-) group (5.3% and 4.2%) (P=0.000) . Subgroup prognostic analysis showed a lower CR rate (P=0.001) and a higher RR (P=0.023) in CD7(+) group comparing to those of CD7(-) group in AML patients with wild type CEBPA. There were no statistical difference between CD7(+) group and CD7(-) group in overall survival (OS) and disease free survival (P>0.05) , while in the CEBPA mutant group the CD7(+) group has higher OS (P=0.019) and DFS (P=0.010) . Based on the CD7 expression and CEBPA mutation, 298 cases were divided into 3 subgroups, named as CD7(+)-CEBPA MT group, CD7(-) and CD7(+)-CEBPA WT group. The 3-year OS of the 3 groups were 80.2%, 48.0% and 30.6%, respectively (P<0.001) , and the 3-year DFS were 74.1%, 37.4% and 22.2%, respectively (P<0.001) . Conclusion: The CEBPA mutation rate was higher in CD7(+) AML patients then that of CD7(-) patients. CD7 expression has opposite prognostic significance in AML patients carrying the wild-type or mutant-type CEBPA. Based on CD7 expression and CEBPA mutation, a new risk stratification model can be established, which is helpful to guide the clinical individualized treatment for AML patients.

Intercomparison of dose enhancement ratio and secondary electron spectra for gold nanoparticles irradiated by X-rays calculated using multiple Monte Carlo simulation codes.

PURPOSE: Targeted radiation therapy has seen an increased interest in the past decade. In vitro and in vivo experiments showed enhanced radiation doses due to gold nanoparticles (GNPs) to tumors in mice and demonstrated a high potential for clinical application. However, finding a functionalized molecular formulation for actively targeting GNPs in tumor cells is challenging. Furthermore, the enhanced energy deposition by secondary electrons around GNPs, particularly by short-ranged Auger electrons is difficult to measure. Computational models, such as Monte Carlo (MC) radiation transport codes, have been used to estimate the physical quantities and effects of GNPs. However, as these codes differ from one to another, the reliability of physical and dosimetric quantities needs to be established at cellular and molecular levels, so that the subsequent biological effects can be assessed quantitatively. METHODS: In this work, irradiation of single GNPs of 50 nm and 100 nm diameter by X-ray spectra generated by 50 and 100 peak kilovoltages was simulated for a defined geometry setup, by applying multiple MC codes in the EURADOS framework. RESULTS: The mean dose enhancement ratio of the first 10 nm-thick water shell around a 100 nm GNP ranges from 400 for 100 kVp X-rays to 600 for 50 kVp X-rays with large uncertainty factors up to 2.3. CONCLUSIONS: It is concluded that the absolute dose enhancement effects have large uncertainties and need an inter-code intercomparison for a high quality assurance; relative properties may be a better measure until more experimental data is available to constrain the models.

[Analysis on treatment of eight extremely severe burn patients in August 2nd Kunshan factory aluminum dust explosion accident].

Objective: To summarize the measures and experience of treatment in mass extremely severe burn patients. Methods: The clinical data and treatment of 8 extremely severe burn patients in August 2 Kunshan factory aluminum dust explosion accident who were admitted in the 100th Hospital of PLA on August 2nd, 2014, were retrospectively analyzed. There were 4 males and 4 females, aging 22-45 (34±7) years, with total burn area of 55%-98% [(89±15)%] total body surface area (TBSA) and full-thickness burn area of 45%-97% [(80±21)%] TBSA. All the 8 patients were accompanied with severe shock, inhalation injury, and blast injury. According to the requirements of former PLA General Logistics Department and Nanjing Military Command, a treatment team was set up including a special medical unit and a special care unit, with Chai Jiake from the First Affiliated Hospital of PLA General Hospital as the team leader, Zheng Qingyi from the 175th Hospital of PLA (the Affiliated Dongnan Hospital of Xiamen University) as the deputy leader, the 100th Hospital of PLA as the treatment base, and burn care, respiratory, nephrology, nursing specialists from the First Affiliated Hospital of PLA General Hospital, and the burn care experts and nursing staff from the 180th Hospital of PLA, 118th Hospital of PLA, 98th Hospital of PLA, and 175th Hospital of PLA, and nurses from the 85th Hospital of PLA, 455th Hospital of PLA, 101th Hospital of PLA, 113th Hospital of PLA as team members. Treatment strategies were adopted as unified coordination by the superior, unified responsibility of team leader, division of labor and cooperation between team members, and multidisciplinary cooperation led by department of burns. With exception of one patient who received deep vein catheterization before admission, the other 7 patients were treated with deep vein catheterization 0.5 to 3.0 hours after admission to correct hypovolemic shock as soon as possible. Eight patients received tracheotomy, and 7 patients were treated with mechanical ventilation by ventilator in protective ventilation strategy with low tide volume and low volume pressure to assist breathing. Fiberoptic bronchoscopy was done one to three times for all the 8 patients to confirm airway injuries and healing status. Escharectomy and Meek dermatoplasty in the extremities of all the 8 patients were performed 3 to 6 days after injury for the first time. Escharectomy, microskin grafting, and covering of large pieces of allogeneic skin on the trunks of 4 patients were performed 11 to 16 days after injury for the second time. The broad-spectrum antibiotics were uniformly used at first time of anti-infective therapy, and then the antibiotics species were adjusted in time. The balance of internal environment was maintained and the visceral functions were protected. One special care unit was on responsibility of only one patient. Psychological intervention was performed on admission. The rehabilitative treatment was started at early stage and in company with the whole treatment. Results: Acute renal injury occurred in 5 patients within 36 hours after injury and their renal function was restored to normal 4 days after injury due to active adjustment of fluid resuscitation program. No pulmonary complications, such as severe pulmonary infection and ventilator-associated pneumonia, occurred in the survived patients. One of the 8 patients died, and the other 7 patients were cured successfully. The wounds were basically healed in 2 patients in 26 or 27 days by 2 or 3 times of operation, and in 5 patients by 4 or 5 times of operation. The basic wound healing time was 26-64 (48±15) days for all the 7 patients. Conclusions: Treatment strategies of unified coordination by the superior, unified responsibility of team leader, division of labor and cooperation between team members, and multidisciplinary cooperation led by department of burns are the bases to successful treatment. Correcting shock as soon as possible is the prerequisite and closing wound as soon as possible is the key to successful treatment. Comprehensive treatment measures, such as maintaining and regulating the function of viscera, improving the body immunity, and preventing and treating the complications, are the important components to successful treatment. It is emphasized that in the treatment of mass extremely severe burn patients, specialist burn treatment should always be in the dominant position, and other related disciplines may play a part in auxiliary function.

[Experience of wound treatment on extremely severe mass burn patients involved in August 2nd Kunshan factory aluminum dust explosion accident].

Objective: To explore experience of wound treatment of extremely severe mass burn patients involved in August 2nd Kunshan factory aluminum dust explosion accident. Methods: On August 2nd, 2014, 98 extremely severe burn mass patients involved in August 2nd Kunshan factory aluminum dust explosion accident were admitted to 20 hospitals in China. The patients with complete medical record were enrolled in the study and divided into microskin graft group with 56 patients and Meek skin graft group with 42 patients. Split-thickness skin in area of residual skin were resected to repair wounds of patients in microskin graft group and Meek skin graft group by microskin grafting and Meek miniature skin grafting, respectively. The residual wound size on 28 days post injury and wound infection after skin grafting of patients in the two groups, and position of donor site of all patients were retrospectively analyzed. Data were processed with t test and chi-square test. Results: The size of residual wound of patients in Meek skin graft group on 28 days post injury was (59±13)% total body surface area (TBSA), which was obviously smaller than that in microskin graft group [(70±14)%TBSA, t=4.379, P<0.05]. Twenty-nine patients in microskin graft group and 11 patients in Meek skin graft group suffered from obvious wound infection after skin grafting. Wounds of patients in two groups were repaired with residual skin around wound in head, trunk, groin, armpit, and uncommon donor sites of scrotum (4 patients), vola (10 patients), and toe or finger web (8 patients). Conclusions: Meek skin graft is the first choice for wound repair of extremely severe burn mass patients, with faster wound healing, less wound infection. Uncommon donor sites of scrotum, vola, and toe or finger web can also be used for wound repair in case of lack of skin.

Simulation on the molecular radiosensitization effect of gold nanoparticles in cells irradiated by x-rays.

Abundant studies have focused on the radiosensitization effect of gold nanoparticles (GNPs) in the cellular environment with x-ray irradiation. To better understand the physical foundation and to initially study the molecular radiosensitization effect within the nucleus, a simple cell model with detailed DNA structure in the central nucleus was set up and complemented with different distributions of single and multiple GNPs in this work. With the biophysical Monte Carlo simulation code PARTRAC, the radiosensitization effects on both physical quantities and primary biological responses (DNA strand breaks) were simulated. The ratios of results under situations with GNPs compared to those without GNPs were defined as the enhancement factors (EFs). The simulation results show that the presence of GNP can cause a notable enhancement effect on the energy deposition within a few micrometers from the border of GNP. The greatest upshot appears around the border and is mostly dominated by Auger electrons. The enhancement effect on the DNA strand breakage becomes smaller because of the DNA distribution inside the nucleus, and the corresponding EFs are between 1 and 1.5. In the present simulation, multiple GNPs on the nucleus surface, the 60 kVp x-ray spectrum and the diameter of 100 nm are relatively more effective conditions for both physical and biological radiosensitization effects. These results preliminarily indicate that GNP can be a good radiosensitizer in x-ray radiotherapy. Nevertheless, further biological responses (repair process, cell survival, etc) need to be studied to give more accurate evaluation and practical proposal on GNP's application in clinical treatment.

3'-UTR polymorphism (rs10434) in the VEGF gene is associated with B-CLL in a Chinese population.

We investigated the relationship between a VEGF genetic polymorphism and B cell chronic lymphocytic leukemia (B-CLL). A total of 102 patients with B-CLL and 124 healthy subjects were included in this study. All individuals were typed for the rs10434 in the vascular endothelial growth factor (VEGF) gene using the TaqMan technique. We found that the A allele and the AA genotype of rs10434 were more frequent in B-CLL patients than in control subjects (0.54 vs 0.34; 27 vs 13%; respectively). VEGF alleles and genotypes segregated similarly in patients at different disease stages according to Rai classification. These results suggest a possible association between the VEGF polymorphism and high-risk B-CLL.

Donor TLR9 gene tagSNPs influence susceptibility to aGVHD and CMV reactivation in the allo-HSCT setting without polymorphisms in the TLR4 and NOD2 genes.

Owing to ethnicity of the population, those best confirmed polymorphisms in the TLR (toll-like receptor)4 and NOD2 genes with significantly prognostic impact on allogeneic hematopoietic SCT (allo-HSCT) seem to be more applicable to Europeans and are nonpolymorphic in the Asian population. The influence of innate immunity gene polymorphisms on the outcomes of allo-HSCT in those populations has been questioned. We evaluated the influence of 10 candidate single nucleotide polymorphisms (SNPs) in the TLR1, TLR2, TLR3, TLR8 and TLR9 genes on the outcomes of allo-HSCT in a Chinese population including 138 pairs of patients and unrelated donors and a second cohort of 102 pairs of patients and HLA-identical sibling donors. We found that two tagSNPs in the TLR9 gene in the donor side, +1174 A/G (rs352139) and +1635 C/T (rs352140), influenced the risk of acute GVHD (aGVHD) and CMV reactivation. Furthermore, the presence of the susceptible haplotype (A-C) in donor may be an informative predicator of worse OS at 5 years compared with those with the G-C and G-T haplotypes (58% vs 82.9%, P=0.024). Our data suggested an unrecognized association between donor TLR9 tagSNPs and the risk of HSCT-related complications in a population without polymorphisms in the TLR4 and NOD2 genes.

Diffuse large B-cell lymphoma with concurrent gastric adenocarcinoma: case report and literature review.

The simultaneous occurrence of diffuse large B-cell lymphoma (DLBCL) and gastric carcinoma is rare. The present case report describes a 61-year-old man with DLBCL at the ileocaecal junction with several metastatic lymph nodes and concurrent gastric intramucosal adenocarcinoma. Both tumours, together with the enlarged lymph nodes, were successfully removed by surgery. At 1 month postoperatively, the patient received chemotherapy consisting of rituximab, cyclophosphamide, vindesine, epirubicin hydrochloride and dexamethasone; he responded well to treatment. Reports published in the literature between January 2006 and March 2011 of other cases of DLBCL combined with concurrent non-haematological malignancies in immunocompetent patients were reviewed. The identification of common factors is important for clarification of the mechanisms of lymphomagenesis and carcinogenesis, as well as the creation of preventive and therapeutic strategies. Such cases highlight the need routinely to perform preoperative imaging studies to exclude other synchronous tumours and, if possible, to biopsy any such masses in order to offer timely and appropriate therapy.

Relationship between TNFA, TNFB and TNFRII gene polymorphisms and outcome after unrelated hematopoietic cell transplantation in a Chinese population.

This study aimed to analyze the association between cytokine gene polymorphisms and outcome following allogeneic hematopoietic SCT (allo-HSCT). A total of 138 unrelated donor/recipient pairs who underwent allo-HSCT from 2001 to 2009 were tested for TNFA-1031 (T>C), -863 (C>A), -857 (C>T), -238 (G>A), TNFB+252 (A>G) and TNFRII codon 196 (T>G) single nucleotide polymorphisms by multiplex SnaPshot analysis. Transplantation involving recipients and/or donors with TNFA-857 C/C genotype or TNFB+252 G allele-positivity resulted in a higher incidence of acute GVHD (aGVHD), which was independent of HLA mismatching. In multivariate analysis, TNFA-857 C/C genotype donors (relative risk (RR)=2.29, P=0.006) and TNFB+252 G allele-positive recipients (RR=1.789, P=0.036) were found to be significantly associated with an increased incidence of aGVHD. TNFA-857 C/C genotype donors (RR=3.748, P=0.002) and TNFB+252 G allele-positive recipients (RR=1.823, P=0.063) were also associated with the development of grades II-IV aGVHD. TNFRII polymorphism in recipients was also related to relapse rate, but no significant associations were found between TNFA, TNFB or TNFRII 196 genotype and cGVHD, relapse or overall survival after transplantation. These results provide the first report of an association between TNFA, TNFB and TNFRII polymorphic features and outcome of allo-HSCT in a Chinese population, and suggest an interaction between TNFA-857 and TNFB+252 genotypes and risk of aGVHD.

The beneficial impact of missing KIR ligands and absence of donor KIR2DS3 gene on outcome following unrelated hematopoietic SCT for myeloid leukemia in the Chinese population.

The effect of natural killer (NK) cell alloreactivity on the outcome of unrelated hematopoietic SCT (HSCT) remains a topic of debate. NK cell alloreactivity after allogeneic HSCT is regulated by killer-cell Ig-like receptors (KIRs). To investigate the influence of KIRs on outcome after unrelated HSCT, we retrospectively analyzed the HLA and KIR genotypes of 116 donor-recipient pairs. We found that missing KIR ligands in recipients were significantly associated with a decreased leukemic relapse risk (P=0.019, HR=0.329), mainly in myeloid disease (P=0.003, HR=0.193). This beneficial effect was seen in AML/myelodysplastic syndrome and also in chronic myeloid leukemia. In myeloid disease, missing KIR ligands also improved 5-year OS (P=0.034, HR=0.430) and disease-free survival (DFS) (P=0.024, HR=0.445). Meanwhile, the presence of donor-activating KIR2DS3 gene was associated with increased relapse risk (P=0.003, HR=5.046), decreased OS (P=0.004, HR=3.181) and DFS (P=0.003, HR=2.919) in myeloid disease. No effect was seen in patients with lymphoid disease. Our study indicated that, in unrelated HSCT for myeloid leukemia, missing KIR ligands in recipients offered a lower relapse risk and a long-term survival advantage. The presence of KIR2DS3 in the donor was an important risk factor for myeloid leukemia.

Activation of the coagulation system in cancerogenesis and metastasation.

The activation of the coagulation system in cancer patients is a well-known phenomenon responsible for recurrent clinical problems. A number of fascinating molecular mechanisms have been recognized showing that the tumor not only activates the coagulation system, but vice versa, activated coagulation proteins are able to induce molecular effects in tumor cells. The molecular basis is the expression of defined membrane receptors by tumor cells that are activated, for example, by thrombin. As the liberation of thrombin from prothrombin is one of the key events in coagulation, it's impact upon biological processes, such as cancerogenesis and metastasation, seems to be a regular pathophysiological consequence. These perceptions are not only interesting for the comprehension of cancerogenesis, metastasation, and clinical phenomena, but they also have a high impact upon modern strategies of tumor therapy. Especially, the development of clinically useful coagulation inhibitors, such as modern low molecular weight heparins or melagatran, created the possibility of therapies that combine cell biological approaches with apoptosis-inducing principals such as chemotherapy. Several clinical studies that demonstrate the implication of these strategies have already been published recently. In this article the cell biological basics for these approaches are reviewed.

Kinetics of slow reversible inhibition of human muscle creatine kinase by planar anions.

The toxicity of NO3- and NO2- to mammals has been widely publicized. However, the kinetic mechanism of inhibition of human muscle creatine kinase by NO3- and NO2- has not been explored. The kinetic theory of the substrate reaction during the modification of enzyme activity previously described by Tsou (Adv. Enzymol. Related Areas Mol. Biol. 1988, 61, 381-436) has been applied to a study of the kinetics of slow reversible inhibition of human muscle creatine kinase by planar anions (NO3- and NO2-). The kinetic equation of the substrate reaction was derived from theoretical analysis and experimental data, then simplified. The microscopic rate constants for the reaction of the inhibitors with the enzyme were obtained from the simplified equation for the substrate reaction in the presence of the inhibitors. The results show that the apparent forward rate constant A is dependent on ATP concentration, indicating competition between the inhibitor (NO3- or NO2-) and ATP. The results also suggest that binding of creatine-MgADP and the anion with the enzyme is very tight, since their binding constants are much higher than those for normal substrates.