[Clinical study of induction chemotherapy followed by allogeneic hematopoietic stem cell transplantation in the treatment of FLT3-ITD(+) acute myeloid leukemia with normal karyotype].

Objective: To assess the efficacy of induction chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of FLT3-ITD(+) acute myeloid leukemia (AML) with normal karyotype. Methods: The clinical data of FLT3-ITD(+) AML patients with normal karyotype in the First Affiliated Hospital of Nanjing Medical University from Jan 2018 to March 2021 were retrospectively analyzed. Results: The study included 49 patients with FLT3-ITD(+)AML, 31 males, and 18 females, with a median age of 46 (16-59) years old. All patients received induction chemotherapy, and 24 patients received sequential allo-HSCT (transplantation group) . The median follow-up time was 465 days, the one-year overall survival (OS) from diagnosis was (70.0 ± 7.4) %, and one-year disease-free survival (DFS) was (70.3±7.4) %. The one-year OS was significantly different between the transplantation group and the non-transplantation group [ (85.2 ± 7.9) % vs (52.6 ± 12.3) %, P=0.049]. but one-year DFS [ (84.7 ± 8.1) % vs (55.2 ± 11.9) %, P=0.061] was not. No significance was found in one-year OS between patients with low-frequency and high-frequency FLT3-ITD(+) (P>0.05) . There were 12 patients with high-frequency FLT3-ITD(+) in the transplantation and the non-transplantation groups, respectively. The one-year OS [ (68.8 ± 15.7) % in the transplantation group vs (26.2 ± 15.3) % in the non-transplantation group, P=0.027] and one-year DFS [ (45.5 ± 21.3) % in the transplantation group vs (27.8±15.8) % in the non-transplantation group, P=0.032] were significantly different between the two groups. Conclusion: Induction chemotherapy followed by allo-HSCT can enhance the prognosis of FLT3-ITD(+) patients, particularly those with FLT3-ITD high-frequency mutation.

[Research progress on exposure levels and toxic pathways of typical persistent organic pollutants in foods].

Dioxins, polybrominated diphenyl ethers, and benzo(a)pyrene are common organic pollutants in food. They have been of concern to academics and government administrations due to high residue and persistence, easy accumulation and strong harmful effects. The National Research Council of the United States of America published Toxicity Testing in the 21st Century: A Vision and Strategy in 2007, which proposed a new concept of toxicity testing that toxicity testing should take full consideration of population exposure data and base on in vitro tests, human cell lines, toxicity pathways and high-throughput screening. Meanwhile, systems biology, bioinformatics and rapid assay technologies will be used to better understand toxicity pathways-the cellular response pathways that can lead to adverse health effects when sufficient perturbing induced by chemicals exposure. The new toxicity testing strategy has changed the traditional testing pattern and has brought a wide impact on the international relevant fields. The European Union, the World Health Organization, and the United States Environmental Protection Agency, the Food and Drug Administration, and the National Center for Toxicological Research have organized relevant discussions and exploratory studies to address the new toxicity testing concept and how to evaluate and utilize the results of traditional toxicity test researches. Compared to the discussion, 'whether to do it', ten years ago, the question, 'how to do it', has become the concern of the current discussion. Therefore, how to respond to the concept of toxicity testing and how to effectively utilize and excavate traditional toxicity test data have been the focus of multi-disciplines and interdisciplinary academia such as toxicology, food hygiene and environmental science. Therefore, this article provides an overview of the exposure levels of dioxin, polybrominated diphenyl ethers and benzo[a]pyrene, which are typical persistent organic pollutants in food in China and the current research status of toxic pathways based on whole animal experiments. The exposure level, toxic effect and toxicity mechanism of three contaminants are analyzed and summarized in order to provide basis for future results based on the 21st century toxicity test compared with traditional tests and data mining analysis of these two kinds of data. Meanwhile, it also lays the foundation for the establishment of a toxicity testing framework based on exposure characteristics, toxic pathways, and biomarkers.

[Management and safety assessment of nanomaterials in food: status and prospects].

The safety assessment of nanomaterials in food is essential for safeguarding supervision and maintaining public health. However, there are still no safety assessment procedures for nanomaterials established in national-level in China and no specific toxicology and safety assessment procedures about nanomaterials for food, too. These factors lead to restriction on food safety protection and supervision. Current methods of evaluating the safety of nanomaterials mainly rely on traditional toxicological assessment that are extrapolated based on animal experiment from high doses to low doses and from animals to humans. These uncertainties restrict the accuracy of safety assessment for nanomaterials and also limit the development of scientific and effective evaluation procedures and regulatory measures. Currently, the key issues need to be solved including exposure assessment and evaluation methods of nanomaterials in food and the established methods of the toxicity test for nanomaterials that are consistent with the objectives of toxicity test in the 21st century vision and strategy. In this article, we reviewed current administrative regulatory, situations, and existing issues of food nanomaterials either in China or some developed countries in order to provide a scientific basis in establishing safety assessment procedures for nanomaterials in food in the future.

[Effect of adipose tissue-derived mesenchymal stem cell transplantation in treatment of liver fibrosis and possible mechanism].

Objective: To investigate the effect of adipose tissue-derived mesenchymal stem cell (ADSC) transplantation in the treatment of liver fibrosis rats and possible mechanism. Methods: Subcutaneous adipose tissue in the inguinal region of rats was collected to isolate ADSCs. The rats with liver fibrosis induced by intraperitoneally injected carbon tetrachloride were divided into cell transplantation group and phosphate buffer saline (PBS) injection group, and the rats which were fed normally were enrolled as negative control group. The rats in the cell transplantation group were given tail vein injection of ADSCs, and those in the PBS injection group were given injection of 0.5 ml PBS. At 7 days after transplantation, blood samples were collected from the inferior vena cava to evaluate liver function; liver tissue was collected to measure the protein expression of hepatocyte growth factor (HGF) and alpha-smooth muscle actin (α-SMA); Masson trichrome staining was used to evaluate intrahepatic collagen deposition. Hepatic stellate cells (HSCs) were collected from the rats with liver fibrosis, and indirect co-culture of HSCs and ADSCs was performed in vitro to analyze the influence of ADSCs on the proliferation and apoptosis of HSCs. The independent samples t-test was used for comparison between groups, and an analysis of variance was used for comparison of means between multiple samples. Results: ADSCs were found in liver tissue in the transplantation group, and compared with the PBS injection group, the transplantation group had significant alleviation in hepatocyte necrosis, vacuolization, and area of fibrosis and significant reductions in the serum levels of aminotransferases, while there was no significant difference in the level of albumin between the two groups. Compared with the PBS injection group, the transplantation group had significant upregulation in the protein expression of HGF and significant downregulation in the protein expression of α-SMA (both P < 0.05). In vitro co-culture for 72 hours showed that ADSCs inhibited the proliferation of HSCs, and there was a significant difference between the co-culture group and the control group with HSCs cultured alone. Caspase-3 immunostaining showed that after co-culture for 72 hours, there was a significant difference in the apoptosis rate of HSCs between the co-culture group and the control group with HSCs cultured alone (23.42% ± 3.02% vs 14.82% ± 3.93%). Conclusion: ADSC transplantation can upregulate the expression of HGF in the liver, promote the apoptosis of HSCs, and thus alleviate liver fibrosis.

[Quantitative structure-activity relationship prediction of carcinogenicity of N-nitroso compounds based on category approach and read-across].

Objective: New quantitative structure-activity relationship (QSAR) method was used to predict N-nitroso compounds (NOCs) carcinogenicity. This could provide evidences for health risk assessment of the chemicals. Methods: Total 74 chemical substances of NOCs were included as target chemicals for this validation study by using QSAR Toolbox based on category approach and read-across. The included 74 NOCs were categorized and subcategorized respectively using "Organic functional groups, Norbert Haider " profiler and "DNA binding by OASIS V.1.1" profiler. Carcinogenicity of rat were used as target of prediction, the carcinogenicity results: of analogues in chemical categories were cross-read to obtain the carcinogenic predictive results of the target chemicals. Results 74 NOCs included 26 nonclic N-nitrosamines, 24 cyclic N-nitrosamines and 24 N-nitrosamides The sensitivity, specificity and concordance of the category approach and read-across for predicting carcinogenicity of 74 NOCs were 75% (48/64), 70%(7/10) and 74% (55/74) respectively. The concordance for noncyclic N-nitrosamines, cyclic N-nitrosamines and N-nitrosamides were 88% (23/26), 71% (17/24) and 63% (15/24) respectively. Conclusion: QSAR based on category approach and read-across is good for prediction of NOCs carcinogenicity, and can be used for high-throughput qualitative prediction of NOCs carcinogenicity.

Combination of a haploidentical SCT with an unrelated cord blood unit: a single-arm prospective study.

We conducted a single-arm prospective study in 50 patients who received the combination of an haploidentical stem cell graft and an unrelated umbilical cord blood unit for the treatment of hematological malignancies. The median time for neutrophil engraftment was 13 days (11-20 days), and for platelets was 15 days (11-180 days). All surviving patients attained complete haploidentical engraftment except three patients who presented a mixed engraftment with increasing cord blood and decreasing haplo mismatch chimerism during the first 4 months after transplantation. The cumulative incidence of grade II-IV acute GVHD was 20%±0.327% at day+100, and the incidence of chronic GVHD was 19.26%±1.0% at 1 year. The 1-year cumulative incidence of relapse was 19.78%±1%, and the TRM was 16.2%±0.54%. At 1 year, overall survival was 78.6%±7.6% and PFS 64.0%±11.0%. The BU/CY-based conditional regimen showed a significant superiority over TBI/CY on PFS (relative risk=5.012, 95% confidence interval, 1.146-21.927, P=0.032). In conclusion, the co-infusion of an unrelated cord blood unit may potentially improve the outcome of haploidentical allogeneic hematopoietic SCT.

Two-photon-pumped frequency-upconverted blue lasing in coumarin dye solution.

Two-photon-pumped (TPP) frequency-upconverted blue lasing of Coumarin 500 dye solution has been experimentally investigated. The shortest lasing wavelength was measured to be ~479 nm from a Coumarin 500 solution in chloroform pumped with ~800-nm laser pulses of ~5-ns duration. The spectral, temporal, and spatial structures as well as the output-input characteristics of TPP cavity lasing were measured with a 1-cm-long Coumarin 500 solution-filled quartz cuvette. The cavity lasing spectral structure and the numbers of longitudinal modes were easily controlled simply by attachment of an optical plate to the output window of the dye-solution cuvette. The net conversion efficiency from the absorbed 800-nm pump pulse energy to the blue-upconverted cavity lasing energy was ~4.8%.

Optical limiting, pulse reshaping, and stabilization with a nonlinear absorptive fiber system.

Optical limiting, pulse reshaping, and stabilization effects have been demonstrated based on a two-photon absorption mechanism with a dye-solution-filled hollow fiber system. The nonlinear absorptive medium is the solution of a new dye, trans-4-[p-(N-hydroxyethyl-N-methylamino)styryl]-N-methylpyridinium iodide (ASPI) in dimethyl sulfoxide, with which we filled a 20-cm-long quartz hollow fiber of 100-mum internal diameter. The input optical signal was a laser pulse train that contained ~30 pulses of 130-ps pulse width. When the input peak intensity reached 400-1000-MW/cm(2) levels, obvious optical limiting could be observed and the envelope of the transmitted pulse train became flatter and broader. By using another new dye solution, 4-[N-(2-hydroxyethyl)-N-(methyl)amino phenyl]-4?-(6-hydroxyhexyl sulfonyl)-stilbene (APSS) in benzyl alcohol, which interacted with a series of ~800-nm laser pulses of ~8-ns pulse width, we obtained a much higher nonlinear absorption coefficient and a superior optical peak-power stabilization effect.

Two-photon resonance-enhanced refractive-index change and self-focusing in a dye-solution-filled hollow fiber system.

The general behavior of two-photon absorption-enhanced refractive-index change in a third-order nonlinear optical medium is briefly described. The nonlinear medium was the solution of a new dye, trans-4-[p-(N-hydroxyethyl-N-methylamino)styryl]-N-methyl pyridinium iodide (ASPI) in dimethyl sulfoxide as the solvent, that was poured into a 20-cm-long quartz hollow fiber of 100-mum internal diameter. This dye solution has a strong two-photon absorption and subsequent upconversion fluorescence emission when excited with 1064-nm laser radiation. When the input peak intensity reached 500-1500-MW/cm(2) levels, obvious changes in beam profiles of the output IR laser beam were observed due to a self-focusing or self-trapping process occurring inside the fiber system. As a result of this process, highly directional frequency-upconverted superradiant lasing output was obtained with a beam size ~5 times smaller than that of a linearly transmitted He-Ne probe laser beam. The demonstrated mechanism can be useful for fiber laser-amplifier and fiber-integrated optics devices.

Phase-conjugate backward stimulated emission from a two-photon-pumped lasing medium.

Optical phase conjugation of the two-photon-pumped frequency upconversion backward stimulated emission of a new dye solution has been demonstrated. When the 1064-nm pump intensity reaches a certain threshold value, a highly directional and phase-conjugate backward stimulated emission at ~616-nm wavelength can be observed. After backward passage through an aberration plate placed in the input pump beam path, the introduced aberration influence (1.6-1.8 mrad) can be entirely compensated by backward stimulated emission with a final beam divergence of only 0.23 mrad. The net conversion efficiency from the absorbed IR pump energy to the backward visible stimulated emission energy can reach 10%.

Three-dimensional laser scanning two-photon fluorescence confocal microscopy of polymer materials using a new, efficient upconverting fluorophore.

Three-dimensional confocal imaging of polymer samples was achieved by the use of two-photon excited fluorescence in both positive and negative contrast modes. The fluorophore was a new and highly efficient two-photon induced upconverter, resulting in improved signal strength at low pumping power. Because of the relatively long wavelength of the excitation source (798 nm from a mode-locked Ti:Sapphire laser), this technique shows a larger penetration depth into the samples than provided by conventional single-photon fluorescence confocal microscopy. Single-photon and two-photon images of the same area of each sample show significant differences. The results suggest the possibility of using two-photon confocal microscopy, in conjunction with highly efficient fluorophores, as a tool to study the surface, interface, and fracture in material science applications.

Two-photon absorption and optical-limiting properties of novel organic compounds.

The optical-limiting behavior and two-photon absorption properties of four novel organic compound solutions in tetrahydrofuran have been investigated. An ultrashort laser source with 0.5-ps pulse width and 602-nm wavelength was employed. The transmissivities of the various 1-cm-thick solution samples have been measured as a function of the beam intensity as well as of the solute concentration. The measured results can be fitted on the assumption that two-photon absorption is the only predominant mechanism causing the observed opticallimiting behavior. Based on the intensity-dependent transmissivity measurements, the molecular two-photon absorption coefficients for the four compounds are presented.

Three-photon-absorption-induced fluorescence and optical limiting effects in an organic compound.

Three-photon-absorption-induced frequency-upconversion f luorescence emission has been observed in a solution of 2,5-benzothiazole 3,4-didecyloxy thiophene (BBTDOT) in tetrahydrofuran, pumped with 10-ns Q-switched 1.06-microm laser pulses. The spectral peak of the observed fluorescence emission is located in the 450-480-nm range, and the intensity dependence of the visible emission on the IR excitation obeys the cubic law. At a higher solute concentration (0.18 M/L) and moderate IR excitation intensity levels (50-200 MW/cm(2)), obvious optical limiting behavior has been observed as a result of three-photon absorption. The measured nonlinear absorption coeff icient and the corresponding molecular three-photon-absorption cross section are gamma= 2.7 x 10(-18) cm(3)/W(2) and sigma'(3) = 8.8 x 10(-76) cm(6) s(2), respectively.

Broadband, multiwavelength stimulated-emission source based on stimulated Kerr and Raman scattering in a liquid-core fiber system.

A novel broadband and multiwavelength stimulated-emission source that consists of a Kerr liquid-filled hollow-fiber system pumped with a monochromatic laser beam is described. The device operates by multiorder stimulated Raman scattering (SRS) and stimulated Kerr scattering (SKS) that result from the high local optical intensity and long gain length provided by the liquid-core hollow-fiber system. A number of transparent liquids have been investigated; CS(2) is identified as the medium that most efficiently generates SKS and SRS. The overall efficiency from the pump input to the coherent output of the system is measured as a function of the fiber parameters (internal diameter and length), inputcoupling focusing length, and pump conditions (pulse duration, spectral width, and wavelength). A number of other experimental results, such as optimized working conditions, output spectral structure, total spectral-covering range, pump-threshold requirements, and the maximum capacity for high pump operation are also presented and discussed.

Difference of spectral superbroadening behavior in Kerr-type and non-Kerr-type liquids pumped with ultrashort laser pulses.

The spectral superbroadening behavior of forward coherent radiation from a 10-cm-long liquid-filled cell is investigated by using an ultrashort (∼0.5 ps) and intense (∼10 GW/cm(2)) laser pulse as the pump source. Five different transparent liquids (heavy water, water, carbon tetrachloride, benzene, and carbon disulfide) have been studied with a special experimental design that can distinguish the predominant contributions from the various possible mechanisms. Under the same pump condition, a very wide and symmetrical superbroadening (continuum) is observed on both the Stokes and the anti-Stokes side of the pump line for non-Kerr-type liquids such as heavy water and water, whereas only a red-shifted spectral broadening can be observed on the Stokes side for Kerr-type liquids such as carbon disulfide and benzene. For an explanation of the latter behavior, the dominant contributions from stimulated Rayleigh-Kerr and Raman-Kerr scattering are proposed.

Gaucher disease: A G+1----A+1 IVS2 splice donor site mutation causing exon 2 skipping in the acid beta-glucosidase mRNA.

Gaucher disease is the most frequent lysosomal storage disease and the most prevalent Jewish genetic disease. About 30 identified missense mutations are causal to the defective activity of acid beta-glucosidase in this disease. cDNAs were characterized from a moderately affected 9-year-old Ashkenazi Jewish Gaucher disease type 1 patient whose 80-year-old, enzyme-deficient, 1226G (Asn370----Ser [N370S]) homozygous grandfather was nearly asymptomatic. Sequence analyses revealed four populations of cDNAs with either the 1226G mutation, an exact exon 2 (delta EX2) deletion, a deletion of exon 2 and the first 115 bp of exon 3 (delta EX2-3), or a completely normal sequence. About 50% of the cDNAs were the delta EX2, the delta EX2-3, and the normal cDNAs, in a ratio of 6:3:1. Specific amplification and characterization of exon 2 and 5' and 3' intronic flanking sequences from the structural gene demonstrated clones with either the normal sequence or with a G+1----A+1 transition at the exon 2/intron 2 boundary. This mutation destroyed the splice donor consensus site (U1 binding site) for mRNA processing. This transition also was present at the corresponding exon/intron boundary of the highly homologous pseudogene. This new mutation, termed "IVS2 G+1----A+1," is the first splicing mutation described in Gaucher disease and accounted for about 3.4% of the Gaucher disease alleles in the Ashkenazi Jewish population. The occurrence of this "pseudogene"-type mutation in the structural gene indicates the role of acid beta-glucosidase pseudogene and structural gene rearrangements in the pathogenesis of this disease.