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Background: Current guidelines on the management strategy for patients with asymptomatic severe aortic stenosis (AS) remain unclear. This uncertainty stems from the lack of data regarding the natural history of these patients. To address this gap, we performed a systematic review and meta-analysis examining the natural history of asymptomatic severe AS patients receiving conservative treatment., Methods: The PubMed, Cochrane, and Embase databases were searched from inception to 24 January 2024 using the keywords "asymptomatic" AND "aortic" AND "stenosis". We included studies examining patients with asymptomatic severe AS. In interventional trials, only data from conservatively managed arms were collected. A one-stage meta-analysis was conducted using individual patient data reconstructed from published Kaplan-Meier curves. Sensitivity analysis was performed for major adverse cardiovascular outcomes in patients who remained asymptomatic throughout follow-up., Results: A total of 46 studies were included (n = 9545). The median time to the development of symptoms was 1.11 years (95% CI 0.90-1.53). 49.36% (40.85-58.59) of patients who were asymptomatic had suffered a major adverse cardiovascular event by 5 years. The median event-free time for heart failure hospitalization (HFH) was 5.50 years (95% CI 5.14-5.91) with 36.34% (95% CI 33.34-39.41) of patients experiencing an HFH by year 5. By 5 years, 79.81% (95% CI 69.26-88.58) of patients developed symptoms (angina, dyspnoea, syncope and others) and 12.36% (95% CI 10.01-15.22) of patients died of cardiovascular causes. For all-cause mortality, the median survival time was 9.15 years (95% CI 8.50-9.96) with 39.43% (CI 33.41-36.40) of patients dying by 5 years. The median time to AVR was 4.77 years (95% CI 4.39-5.17), with 52.64% (95% CI 49.85-55.48) of patients requiring an AVR by 5 years., Conclusion: Our results reveal poor cardiovascular outcomes for patients with asymptomatic severe AS on conservative treatment. A significant proportion eventually requires an AVR. Further research is needed to determine if early intervention with AVR is more effective than conservative treatment., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Polycystic ovary syndrome (PCOS) infertility has attracted great attention from researchers due to its high incidence. Numerous studies have shown that Chinese medicine is effective in treating this disease, but there is a wide variety of Chinese medicine therapies available, and there is a lack of comparative evaluation of the efficacy of various Chinese medicine combination therapies in the clinic, which requires further in-depth exploration. This study aims to evaluate the efficacy of a combined traditional Chinese medicine (TCM) therapy for the treatment of infertility with PCOS using network meta-analysis (NMA)., Methods: In PubMed, web of Science, Cochrane Library, Embase, China Knowledge Network, Wanfang Data, VIP Database, China Biomedical Literature Database (SinoMed) databases, searchs were conducted for information about the randomized controlled trials (RCTs) of combined TCM therapy for the treatment of infertility with PCOS. Quality evaluation was performed using the Cochrane 5.3 risk of bias assessment tool, and NMA using Stata 16.0., Results: This study comprised 28 RCTs using 8 combined TCM therapies in total. The results of the NMA showed that moxibustion + herbal, fire acupuncture + herbal, acupuncture + herbal, electroacupuncture + herbal, and acupoint application + herbal improved the clinical pregnancy rate better than acupuncture, herbal, and western medicines monotherapy (P < .05). Additionally, ear point pressure + herbal enema + herbal, acupuncture and moxibustion + herbal, fire acupuncture + herbal, and acupuncture + herbal improved the ovulation rate better than acupuncture, herbal, and western medicines monotherapy (P < .05). Moxibustion + herbal, fire acupuncture + herbal, and acupuncture + herbal are the 3 most effective therapies for improving the clinical pregnancy rate. Fire acupuncture + herbal, acupuncture + herbal, and ear point pressure + herbal enema + herbal are the 3 most effective therapies for improving the ovulation rate., Conclusion: The combined TCM therapy demonstrated better efficacy for the treatment of infertility with PCOS compared to acupuncture, herbal, and western medicines monotherapy. However, the optimal treatment therapy varied depending on the outcome indicators. Further large sample, high-quality, and standardized RCTs are needed to verify these findings., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Phosphatases can dephosphorylate phosphorylated kinases, leading to their inactivation, and ferroptosis is a type of cell death. Therefore, our aim is to identify phosphatases associated with ferroptosis by analyzing the differentially expressed genes (DEGs) of the Luminal A Breast Cancer (LumABC) cohort from the Cancer Genome Atlas (TCGA). An analysis of 260 phosphatase genes from the GeneCard database revealed that out of the 28 DEGs with high expression, only the expression of pyruvate dehydrogenase phosphatase 2 (PDP2) had a significant correlation with patient survival. In addition, an analysis of DEGs using gene ontology, Kyoto Encyclopedia of Genes and Genomes and gene set enrichment analysis revealed a significant variation in the expression of ferroptosis-related genes. To further investigate this, we analyzed 34 ferroptosis-related genes from the TCGA-LumABC cohort. The expression of long-chain acyl-CoA synthetase 4 (ACSL4) was found to have the highest correlation with the expression of PDP2, and its expression was also inversely proportional to the survival rate of patients. Western blot experiments using the MCF-7 cell line showed that the phosphorylation level of ACSL4 was significantly lower in cells transfected with the HA-PDP2 plasmid, and ferroptosis was correspondingly reduced (p < 0.001), as indicated by data from flow cytometry detection of membrane-permeability cell death stained with 7-aminoactinomycin, lipid peroxidation, and Fe2+. Immunoprecipitation experiments further revealed that the phosphorylation level of ACSL4 was only significantly reduced in cells where PDP2 and ACSL4 co-precipitated. These findings suggest that PDP2 may act as a phosphatase to dephosphorylate and inhibit the activity of ACSL4, which had been phosphorylated and activated in LumABC cells. Further experiments are needed to confirm the molecular mechanism of PDP2 inhibiting ferroptosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Gankyrin is found in high levels in triple-negative breast cancer (TNBC) and has been established to form a complex with the E3 ubiquitin ligase MDM2 and p53, resulting in the degradation of p53 in hepatocarcinoma cells. Therefore, this study sought to determine whether gankyrin could inhibit ferroptosis through this mechanism in TNBC cells. The expression of gankyrin was investigated in relation to the prognosis of TNBC using bioinformatics. Co-immunoprecipitation and GST pull-down assays were then conducted to determine the presence of a gankyrin and MDM2 complex. RT-qPCR and immunoblotting were used to examine molecules related to ferroptosis, such as gankyrin, p53, MDM2, SLC7A11, and GPX4. Additionally, cell death was evaluated using flow cytometry detection of 7-AAD and a lactate dehydrogenase release assay, as well as lipid peroxide C11-BODIPY. Results showed that the expression of gankyrin is significantly higher in TNBC tissues and cell lines, and is associated with a poor prognosis for patients. Subsequent studies revealed that inhibiting gankyrin activity triggered ferroptosis in TNBC cells. Additionally, silencing gankyrin caused an increase in the expression of the p53 protein, without altering its mRNA expression. Co-immunoprecipitation and GST pull-down experiments indicated that gankyrin and MDM2 form a complex. In mouse embryonic fibroblasts lacking both MDM2 and p53, this gankyrin/MDM2 complex was observed to ubiquitinate p53, thus raising the expression of molecules inhibited by ferroptosis, such as SLC7A11 and GPX4. Furthermore, silencing gankyrin in TNBC cells disrupted the formation of the gankyrin/MDM2 complex, hindered the degradation of p53, increased SLC7A11 expression, impeded cysteine uptake, and decreased GPX4 production. Our findings suggest that TNBC cells are able to prevent cell ferroptosis through the gankyrin/p53/SLC7A11/GPX4 signaling pathway, indicating that gankyrin may be a useful biomarker for predicting TNBC prognosis or a potential therapeutic target., (© 2023. The Author(s).)

A retrospective analysis was conducted based on the clinical data from 60 patients older than 16 years from January 2016 to January 2021. All the patients were newly diagnosed with severe aplastic anemia (SAA) with an absolute neutrophil count (ANC) of zero. We compared the hematological response and survival of haploidentical-allogeneic hematopoietic stem cell transplantation (HID-HSCT) (n = 25) and intensive immunosuppressive therapy (IST) (n = 35) treatments. At six months, the overall response rate and complete response were significantly higher in the HID-HSCT group than those in the IST group (84.0% vs. 40.0%, P = 0.001; 80.0% vs. 17.1%, P = 0.001). With a median follow-up of 18.5 months (4.3~30.8 months), patients in the HID-HSCT group had longer overall survival and event-free survival (80.0% vs. 47.9%, P = 0.0419; 79.2% vs. 33.5%, P = 0.0048). These data suggested that HID-HSCT might be an effective alternative treatment option for adult patients with SAA with an ANC of zero, which requires further validation in an additional prospective study., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Proteasomes are overexpressed in multiple myeloma (MM) and proteasomal inhibitors (PIs) have been widely used for the treatment of MM. PIs are reported to induce MM cell apoptosis but impair necroptosis. In the present study, we found that PIs MG132 and bortezomib induce MM cell pyroptosis, a novel type of cell death, in a GSDME-dependent manner. Lack of GSDME totally blocks PI-induced pyroptosis. Interestingly, we found that Caspase-3/6/7/9 are all involved in pyroptosis triggered by PIs because the specific inhibitor of each caspase ablates GSDME activation. PIs markedly reduce mitochondrial membrane potential. Moreover, PIs disrupt the interaction of Bcl-2 and BAX, induce cytochrome c release from mitochondria to cytosol and activate GSDME. Furthermore, we found that overexpression of an N-terminal portion of GSDME suffices to release cytochrome c from mitochondria and to activate Caspase-3/9, suggesting N-GSDME might penetrate the mitochondrial membrane. Consistent with Bcl-2 inhibition, BAX can induce MM cell pyroptosis in a GSDME-dependent manner. In accordance with these findings, inhibition of Bcl-2 synergizes with PIs to induce MM cell pyroptosis. Therefore, the present study indicates that PIs trigger MM cell pyroptosis via the mitochondrial BAX/GSDME pathway and provides a rationale for combined treatment of MM with Bcl-2 and proteasome inhibitors to increase therapeutic efficiency via induction of pyroptosis., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

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.

Background: Fish are the primary source of protein and docosahexaenoic acid (DHA) for pregnant women and children, but methylmercury (MeHg) pollution is the potential hazard of fish consumption. In risk assessments, the bio-accessibility of MeHg is usually assumed to be 100%, which could lead to overestimation of dietary exposure., Method: An existing PBTK model was adapted to estimate parameters of the bio-accessibility based on MeHg exposure data from a cohort of 397 Chinese pregnant women. The posterior distributions of parameters were determined by using the ABC - MCMC. RMSEP and Spearman's rank correlation coefficients (Rho) were calculated to determine the goodness of model fitting. The Monte Carlo analysis was performed for the parameter distributions to estimate the model variability., Result: The median of daily MeHg intake and maternal MeHg levels were 0.018 μg/kg bw and 3.01 μg/kg in the early and middle terms of pregnancy. The estimated bio-accessibility of freshwater fish, marine fish and others were 46.1, 17.3 and 58.2%, separately. The RMSEP improved from 11.18 to 2.54 and the Rho improved from 0.19 to 0.22 after bio-accessibility optimization. The model variability was estimated to be 2.6., Conclusion: The bio-accessibility estimated in this study was comparable to that determined in previous in vitro studies. The optimized model could improve the prediction performance on the MeHg body burden by dietary exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disease. Allogeneic hematopoietic stem cell transplantation from a matched sibling donor (MSD-HSCT) and intensive immunosuppressive therapy (IST) are 2 major comparable treatments for SAA. As the addition of eltrombopag (EPAG) to standard IST therapy has greatly improved the survival prognosis of SAA, whether MSD-HSCT or IST/EPAG is the better choice has become a matter of debate. A study was performed involving 99 patients with newly diagnosed acquired SAA from 5 medical centers, including 48 MSD-HSCT cases and 51 IST/EPAG cases, which consisted of rabbit antithymocyte globulin or porcine-antilymphocyte globulin, cyclosporine plus eltrombopag. The results suggested that patients treated with MSD-HSCT or IST/EPAG had similar overall survival (OS) rates exceeding 95% (P = .97). However, the event-free survival rate (EFS) of IST/EPAG (71.0%) was significantly lower than that of MSD-HSCT (89.6%), P = .04. Subgroup analysis indicated that the OS of the MSD-HSCT group was superior to that of the IST/EPAG group (100% versus 85.7%, P = .04) among those with very severe aplastic anemia (VSAA). Both the complete response rate (CR) and overall response rate (OR) with MSD-HSCT were significantly higher than those with IST/EPAG (CR: 79.2% versus 15.7%, P < .001; OR: 97.9% versus 72.6%, P = .001). In conclusion, IST/EPAG or MSD-HSCT treatment achieves an equally high OS in SAA, but MSD-HSCT leads to a better OS in patients with VSAA and shows advantages in improving EFS and accelerating hematopoietic reconstruction in patients with SAA., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to report., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Over the past two decades, both transport modes as well as overweight/obesity have changed dramatically among students in China, but their relationships are not clear. This study aimed to investigate modes of transport to school and their associations with the weight status of Chinese students. Methods: A cross-sectional study was conducted with non-resident students aged 6 to 17 years from all 16 districts across Shanghai, China in October and November 2019. Information about sociodemographic characteristics and the models of travel to school among students was investigated using an online, self-administered, structured questionnaire (or those assisted by their parents). Weight and height were measured by school health workers, and the Chinese standard age adjusted BMI (weight/height 2 ) was used to classify students' weight status. Cumulative logistic regression modelling was used to examine the relationships. Results: The main mode of transport to school was an active mode (46.5%, defined as walking, bicycling, or public transport), followed by an inactive mode of transport (30.5%, defined as a car or bicycle as a passenger), and a combination of both modes (23%). About one-third of the students were overweight or obese and 5% were underweight. No statistically significant association between transport modes and weight status was found in this study. Conclusions: In Shanghai, close to one-third of children travel to school by an inactive mode of transport. The findings of this study did not support the notion that an active mode to school could be beneficial for preventing overweight/obesity in students in China.

This study aimed to develop a Chinese Healthy Eating Index for School-age Children (CHEI-SC), apply it in the 2011 China Health and Nutrition Survey (CHNS) to assess dietary quality, and compared it with our former developed index named CHEI. Data of 3-day 24-hour diet recalls and household food inventory survey from 1600 school-age children in CHNS-2011 were used to develop the CHEI-SC, using the methods of standard portion size, energy-density-based approach, and least restrictive approach. The CHEI-SC included 19 components with a total score (T-score) ranging from 0 to 100. The investigated children had a median score of 49.6. Children with a higher T-score were more likely to have higher social economic status (SES), higher level of urbanisation, fewer family size, and regularly attending school. The CHEI-SC was able to assess dietary quality of Chinese school-age children, was sensitive to demographics, and more comprehensive and accurate than the CHEI.

Objective: To investigate the clinical characteristics, laboratorial and bone marrow pathological features of primary thrombocytopenia (ET) patients with different mutations of CALR, JAK2 and MPL genes., Methods: The chinical data of 120 cases of ET in Jiangsu provincial people's hospital/ The First Affiliated Hospital of Nanjing Medical University from January 2015 to December 2017 were collected and analyzed, including 76 cases with JAK2 gene mutation, 40 cases with CALR gene mutation, 2 cases with MPL gene mutations, 2 cases without gene mutation., Results: Among the ET patients, compared with the JAK2 gene mutation, CALR gene mutation showed statistically significant deareament of white blood cells and hemoglobin (P=0.001, P=0.01) and the male platelets in CALR group showed significant increament (P=0.04). Fourthermore, the average number of megakaryocytes and its cluster numbers in each hight power field of vision showed statistically significant decreament in CALR group as compared with JAK2 group (P=0.001, P=0.001), and thrombotic events in CALR group were signicantly lower than those in JAK2 group (7.5% vs 18.4%) (P=0.03)., Conclusion: Mutations of CALR, JAK2 have different clinical characteristics and blood pathological changes of Chinese ET patients, and their clinical significance is worth to explore.

We introduce the use of laser ablation to develop a multi-drug encapsulating theranostic nanoformulation for HIV-1 antiretroviral therapy. Laser ablated nanoformulations of ritonavir, atazanavir, and curcumin, a natural product that has both optical imaging and pharmacologic properties, were produced in an aqueous media containing Pluronic® F127. Cellular uptake was confirmed with the curcumin fluorescence signal localized in the cytoplasm. Formulations produced with F127 had improved water dispersibility, are ultrasmall in size (20-25 nm), exhibit enhanced cellular uptake in microglia, improve blood-brain barrier (BBB) crossing in an in vitro BBB model, and reduce viral p24 by 36 fold compared to formulations made without F127. This work demonstrates that these ultrasmall femtosecond laser-ablated nanoparticles are effective in delivering drugs across the BBB for brain therapy and show promise as an effective method to formulate nanoparticles for brain theranostics, reducing the need for organic solvents during preparation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the prognosis of adult severe aplastic anemia (SAA) patients with absolute neutrophil count (ANC) values of zero prior to immunosuppressive therapy (IST). Methods: Patients with ANC values of zero prior to IST were separated from very SAA and analyzed in a prospective study. All patients received IST with rabbit anti-thymocyte globulin (ATG) and cyclosporine (CsA). Results: A significantly lower response rate (RR) was identified in patients with ANC = 0 prior to IST when compared to patients with SAA after both 3 and 6 month periods or compared to those with vSAA at 3 months only. The efficacy of IST was inversely related to ANC = 0. The overall survival rate of the 'zero' group was significantly lower than that of the vSAA or SAA groups. Overall survival was closely associated with response to IST, and was inversely related to ANC = 0. Discussion: In SAA patients, ANC is associated with prognosis, the elucidated overall survival improvement in patients without ANC = 0 occurred in conjunction with decreased infection-related mortality. Our study revealed that adult patients with ANC = 0 prior to IST responded poorly to IST, suggesting that having a very low number of neutrophils was a highly predictive factor for efficacy and survival of SAA patients treated with IST. Conclusion: Adult SAA patients with ANC = 0 had a very poor prognosis and new therapeutic regimens may result in better outcome for these patients.

We report the observation of backward stimulated Mie scattering (SMS) due to light-field induced spatial redistribution of self-assembled nanospheres of a two-photon resonant organic chromophore in water, pumped by ∼10-ns laser pulses of ∼816-nm wavelength. The pump-energy threshold for generating backward stimulated scattering in such a system is remarkably lower than that in pure water. The gain of backscattering originates from an induced Bragg grating that reflects partial energy from the pump beam into the backward Mie scattering beam. Based on the experimental fact that the time-delay of the SMS pulse onset depends on both the pump level and the viscosity of the solvent, a physical model of SMS generation is proposed. Our experimental results have shown that the major contribution to the formation of an induced Bragg grating is spatial redistribution of nanoparticles suspended in the liquid. These nanoparticles are driven by a force that is proportional to the intensity gradient of the standing-wave field resulting from interference between the forward pump beam and the backward Mie scattering beam. When the nanoparticle motion is frozen in a gel-like medium, no SMS is observed, which experimentally supports the validity of the proposed physical model.

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.

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.

The Chinese Healthy Eating Index (CHEI) is a measuring instrument of diet quality in accordance with the Dietary Guidelines for Chinese (DGC)-2016. The objective of the study was to evaluate the validity and reliability of the CHEI. Data from 12,473 adults from the China Health and Nutrition Survey (CHNS)-2011, including 3-day-24-h dietary recalls were used in this study. The CHEI was assessed by four exemplary menus developed by the DGC-2016, the general linear models, the independent t -test and the Mann-Whitney U -test, the Spearman's correlation analysis, the principal components analysis (PCA), the Cronbach's coefficient, and the Pearson correlation with nutrient intakes. A higher CHEI score was linked with lower exposure to known risk factors of Chinese diets. The CHEI scored nearly perfect for exemplary menus for adult men (99.8), adult women (99.7), and the healthy elderly (99.1), but not for young children (91.2). The CHEI was able to distinguish the difference in diet quality between smokers and non-smokers ( P < 0.0001), people with higher and lower education levels ( P < 0.0001), and people living in urban and rural areas ( P < 0.0001). Low correlations with energy intake for the CHEI total and component scores (|r| < 0.34, P < 0.01) supported the index assessed diet quality independently of diet quantity. The PCA indicated that underlying multiple dimensions compose the CHEI, and Cronbach's coefficient α was 0.22. Components of dairy, fruits and cooking oils had the greatest impact on the total score. People with a higher CHEI score had not only a higher absolute intake of nutrients ( P < 0.001), but also a more nutrient-dense diet ( P < 0.001). Our findings support the validity and reliability of the CHEI when using the 3-day-24-h recalls., Competing Interests: The authors declare no conflict of interest.

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.

Objective: To examine the association of maternal dietary patterns during pregnancy with gestational diabetes mellitus (GDM) in northern China., Methods: The dietary intakes of pregnant women were recorded twice by 24-hour dietary recalls for three days prior to having been diagnosed with GDM, at 5-15 and 24-28 gestational weeks, respectively. GDM was diagnosed, and serum glycosylated hemoglobin (HbA1c) was measured at 24-28 weeks. Dietary patterns were assessed by factor analysis. The association of the dietary pattern with GDM and HbA1c was examined by multiple logistic models., Results: Of 753 participants, 64 (8.5%) were diagnosed with GDM. Four dietary patterns were identified: Western pattern (dairy, baked/fried food and white meat), traditional pattern (light-colored vegetables, fine grain, red meat and tubers), mixed pattern (edible fungi, shrimp/shellfish and red meat) and prudent pattern (dark-colored vegetables and deep-sea fish). Compared with the prudent pattern, both the Western pattern and the traditional pattern were associated with an increased risk of GDM (aOR = 4.40, 95% CI: 1.58-12.22; aOR = 4.88, 95% CI: 1.79-13.32) and a high level of HbA1c (aOR = 12.37, 95% CI: 1.47-103.91; aOR = 26.23, 95% CI: 2.54-270.74). Compared to the lowest quartile (Q), Q3 of the Western pattern scores and Q3-Q4 of the traditional pattern scores were associated with a higher risk of GDM., Conclusion: The consumption of the Western pattern or the traditional pattern during pregnancy may increase the risk of GDM., (Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

In recent years, photoacoustic tomography (PAT) is increasingly used in biomedical research, as it allows for direct visualization of optical absorption in deep tissue. In addition to vascular and hemodynamic imaging using endogenous contrasts, PAT is also capable of imaging neural and molecular dynamics with extrinsic contrasts. While near-infrared (NIR)-absorbing contrasts are preferred for deep tissue imaging, compared to visible-light-absorbing contrasts, they are much harder to design and synthesize with good environmental stability. We introduce here a new PAT mode which utilizes nonlinear multiphoton upconversion of NIR light in situ to visible light, thus exciting locally a dye that can generate strong photoacoustic signal. This approach allows to take advantage of a large library of visible-light-absorbing dyes that can enable functional imaging, such as imaging of voltage, oxygen, pH, and ion channel activities. Two types of upconversion materials are utilized in this work: 1) a two-photon absorbing and emitting dye that is efficiently excited by NIR nanosecond laser pulses to enable pulsed laser-based PAT (pulsed-PAT); and 2) rare-earth containing inorganic nanocrystals that absorb continuous-wave (CW) NIR light by sequential multiphoton absorption through real intermediate states to enable intensity-modulated CW laser-based PAT (CW-PAT). Since both cases produce highly localized nonlinear photoacoustic signal, which has very weak scattering in tissue, we can achieve high contrast 3-D volume imaging of deep tissues. In this study, we validated the principle of our approach in different PAT modes and successfully detected enhanced photoacoustic signals from a visible-light-absorbing dye embedded deep in tissue. With vast variety of functionalized organic dyes operating in the visible range, our mode of nonlinear photoacoustic imaging will find great applications in preclinical and clinical researches., Competing Interests: Notes The authors declare no competing financial interest.

The objective of this study was to develop a Chinese Healthy Eating Index (CHEI) based on the updated Dietary Guidelines for Chinese (DGC-2016) and to apply it in the 2011 China Health and Nutrition Survey (CHNS-2011) to assess diet quality and its association with typical sociodemographic/economic factors. Data from 14,584 participants (≥2 years) from the CHNS-2011, including three 24-h dietary recalls and additional variables, were used to develop the CHEI. The standard portion size was applied to quantify food consumption. The CHEI was designed as a continuous scoring system, comprising 17 components; the maximum total score is 100. The mean, 1st and 99th percentiles of the CHEI score were 52.4, 27.6 and 78.3, respectively. Young and middle-aged adults scored better than the elderly. Diet insufficiency was chiefly manifested in fruits, dairy, whole grains and poultry; diet excess was mainly reflected in red meat, cooking oils and sodium. The CHEI was positively associated with education and urbanization levels; current smokers and unmarried people obtained relative low CHEI scores. Occupation and body mass index (BMI) were also related to the CHEI. Our findings indicate that the CHEI is capable of recognizing differences in diet quality among the Chinese, and it is sensitive to typical sociodemographic/economic factors.

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.

Age structures and spatial distribution patterns of Quercus variabilis populations were analyzed across geographical gradients (latitude, longitude and altitude) by using the size-grading method and the ratio of variance to mean. The results showed as following: Over the horizontal gradient, the northern, middle, southern and western populations of Q. variabilis exhibited an inverse-J shape, but the eastern populations declined. The spatial patterns of adult individuals were all clumped except the northern populations which were randomly distributed. Juveniles were clumped in the northern, middle and western populations, but were randomly distributed in the southern and eastern populations. The aggregation intensity of juveniles across latitude decreased with the order as the central, northern and southern populations, but as the central, southern and northern populations for adult individuals. The aggregation intensity of both juveniles and adults across longitude followed a decreased order as the central, western and eastern populations. Along the altitudinal gra-dient, the inverse-J type occurred only in the low- and middle-altitude populations, but populations in the high altitude declined. The juveniles in populations among altitude gradient all were clumped, but the adults were all clumped except the low-altitude populations which were randomly distributed. The aggregation intensities of both juveniles and adults were higher in the middle than the other altitudinal populations. Compared with adults, juveniles generally had higher aggregation intensities across various geographical gradients. Our results revealed that the age structure and spatial distribution pattern of Q. variabilis were mainly determined by environment variation across geographical gradients and the species' biological property, which supported the central-marginal hypothesis.

The phenomenon of luminescence concentration quenching exists widely in lanthanide-based luminescent materials, setting a limit on the content of lanthanide emitter that can be used to hold the brightness. Here, we introduce a concept involving energy harvesting by a strong absorber and subsequent energy transfer to a lanthanide that largely alleviates concentration quenching. We apply this concept to Nd 3+ emitters, and we show both experimentally and theoretically that the optimal doping concentration of Nd 3+ in colloidal NaYF 4 :Nd upconverting nanoparticles is increased from 2 to 20 mol% when an energy harvestor organic dye (indocyanine green, ICG) is anchored onto the nanoparticle surface, resulting in ∼10 times upconversion brightness. Theoretical analysis indicated that a combination of efficient photon harvesting due to the large absorption cross section of ICG (∼30 000 times higher than that of Nd 3+ ), non-radiative energy transfer (efficiency ∼57%) from ICG to the surface bound Nd 3+ ions, and energy migration among the Nd 3+ ions was able to activate Nd 3+ ions inside the nanoparticle at a rate comparable with that of the pronounced short-range quenching interaction at elevated Nd 3+ concentrations. This resulted in the optimal concentration increase to produce significantly enhanced brightness. Theoretical modeling shows a good agreement with the experimental observation. This strategy can be utilized for a wide range of other lanthanide-doped nanomaterials being utilized for bioimaging and solar cell applications.

Exploiting synergistic cooperation between multiple sources of optical nonlinearity, we report the design, synthesis, and nonlinear optical properties of a series of electron-rich thiophene-containing donor-acceptor chromophores with condensed π-systems and sterically regulated inter-aryl twist angles. These structures couple two key mechanisms underlying optical nonlinearity, namely, (i) intramolecular charge transfer, greatly enhanced by increased electron density and reduced aromaticity at chromophore thiophene rings and (ii) a twisted chromophore geometry, producing a manifold of close-lying excited states and dipole moment changes between ground and excited states that are nearly twice that of untwisted systems. Spectroscopic, electrochemical, and nonlinear Z-scan measurements, combined with quantum chemical calculations, illuminate relationships between molecular structure and mechanisms of enhancement of the nonlinear refractive index. Experiment and calculations together reveal ground-state structures that are strongly responsive to the solvent polarity, leading to substantial negative solvatochromism (Δλ ≈ 10(2) nm) and prevailing zwitterionic/aromatic structures in the solid state and in polar solvents. Ground-to-excited-state energy gaps below 2.0 eV are obtained in condensed π-systems, with lower energy gaps for twisted versus untwisted systems. The real part of the second hyperpolarizability in the twisted structures is much greater than the imaginary part, with the highest twist angle chromophore giving |Re(γ)/Im(γ)| ≈ 100, making such chromophores very promising for all-optical-switching applications.

We report a new class of hybrid π-electron chromophores with a large, sign-tunable third-order nonlinear optical (NLO) response, achieved via cooperative coupling of cyanine dye bond-length alternation effects with the rich density of states in zwitterionic twisted π-system chromophores. A combined synthetic, linear/nonlinear spectroscopic, and quantum chemical study reveals exceptional third-order response exceeding the sum of the individual chromophore contributions.

The usefulness of flow cytometric variable β-chain repertoire (FC-Vβ) and T-cell receptor gene rearrangement (TCR-GR) analyses for differentiating T-cell large granular lymphocytic leukemia (T-LGLL) from reactive T-large granular lymphocyte (T-LGL) lymphocytosis has been insufficiently studied to date. In this study, we analyzed the diagnostic value of TCR-GR and FC-Vβ analysis in T-LGLL, and compared these results. In our study, FC-Vβ analysis was positive in all cases of T-LGLL, and clonality assessment of FC-Vβ had equal sensitivity and specificity to GeneScanning analysis but was more sensitive than heteroduplex analysis. Suspected T-cell clonality can best be addressed by evaluating two TCR targets (TCRβ and TCRγ), either in parallel or consecutively. Signal transducer and activator of transcription 3 (STAT3) mutation may provide a diagnostic tool for classifying some cases of T-LGL lymphocytosis as true T-LGLL. Our results further demonstrate a significant correlation of STAT3 mutation with pure red cell aplasia, neutropenia, hepatomegaly, β2-microglobulin and anemia.

The design, synthesis, and supramolecular organization of a nanocomposite in which nanoscale excitonic interactions between quantum dots and the chiral polymer dramatically enhance the optical activity is reported. This material is highly suitable for application in the emerging field of chiral photonics., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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.

Through the applications of high-sensitivity flow cytometry of FLAER and the treatment of eculizumab, it is necessary to understand of paroxysmal nocturnal hemoglobinuria (PNH) from a new point of view. The results of studies demonstrate that treatment with eculizumab alters the natural history of PNH by virtually eradicating thromboembolic complications, inhibiting of intravascular hemolysis and reducing or eliminating transfusion requirements. Eculizumab treatment may also reduce disease-related mortality. This review focuses on the studies to define the relationship between PNH and bone marrow failure syndromes and to characterize the long-term outcome of patients with PNH treated with eculizumab. New therapeutic strategies aimed at controlling extravascular and intravascular hemolysis are discussed.

Objective: To evaluate the efficacy and safety of dose-reduced decitabine for the lower risk myelodysplastic syndrome (MDS) patients with transfusion dependent., Methods: Twenty-five cases of lower risk (low or intermediate-1 risk in IPSS risk group) MDS patients with transfusion dependence from November 2009 to September 2012 were treated by dose-reduced decitabine (20 mg/m(2) intravenously once daily for 3 days). And their efficacy, side effects, quality-of-life and survival rate were evaluated., Results: Among them, the responses included complete remission (CR, n = 3, 12%), transfusion independence (n = 4, 16%), hematologic improvement (HI, n = 8, 32%) and stable disease (SD, n = 2, 8%). And the overall response rate (ORR) was 68% (17/25) . Among 11 cases available for cytogenetic evaluation, 1 achieved partial cytogenetic remission (PRc). IV grade hematologic toxicity rate was 48% (12/25) and III-IV grade infection rate 20% (5/25). No severe hematologic toxicity was observed. After treatment, the Karnofsky performance score (KPS) increased from 47 ± 16 to 66 ± 22 (P = 0.001); more patients were reclassified as WPSS ≤ 1 (44%vs 16%, P = 0.031) or MDACC score ≤ 7 (64% vs 8%, P = 0.022). The median follow-up time was 467(14-881) d. The 100 and 600-day expected survive rates of low and intermediate -1 risk in IPSS risk group were 100% versus 95.2% and 100% versus 90.5%., Conclusions: Dose-reduced decitabine is well-tolerated and effective in transfusion dependent MDS patients in IPSS-lower risk. There is a low rate of severe hematologic toxicity and early mortality. It may prolong their survival time.

Objective: To explore the impact of prior-to-transplantation induction therapy (IT) on patient outcome after allogeneic hematopoietic stem-cell transplantation (Allo-HSCT) for higher-risk myelodysplastic syndromes (MDS)., Methods: A total of 49 consecutive patients underwent Allo-HSCT for MDS between November 2002 and December 2012. Twenty-six lower-risk MDS cases received supportive therapy (ST). And 17/23 cases of higher-risk MDS received IT prior to transplantation while another 6 only with ST. Their survival, relapse rate and incidence of transplantation-related mortality (TRM) were retrospectively analyzed according to International Prognostic Scoring System (IPSS) scores and marrow blast count., Results: The 5-year cumulative overall survival (OS), disease-free survival (DFS), relapse rate and incidence of transplantation related mortality (TRM) were 59.9%, 59.2%, 10.5% and 31.8% during a median follow-up period of 24.4 (6.2-72.0) months. The OS and DFS of higher-risk group with IT, ST and lower-risk group were different (72.1% vs 16.7% vs 68.1%, P = 0.028; 72.1% vs 16.7% vs 67.9%, P = 0.030). And the OS and DFS of higher-risk group with IT were similar to those of lower-risk group (P = 0.526,0.504) . For the higher-risk group, the patients on IT had improved survival than those on ST in terms of OS and DFS (both P = 0.020). Moreover, the OS and DFS of remission group were higher than non-remission group in patients on IT (both 100% vs 46.7%, P = 0.049). The number of marrow blasts significantly decreased after IT (P = 0.010) without increased TRM (28.9% vs 33.6%, P = 0.612)., Conclusion: Induction therapy prior to Allo-HSCT for MDS may reduce clone burden and improve the outcomes of higher-risk MDS without increased TRM.

Myelodysplastic syndrome (MDS) is a heterogeneous disease characterized by dysplasia and ineffective hematopoiesis. The dysplasia is crucial in the diagnosis of MDS, but the morphologic abnormalities of bone marrow cells are not specific for MDS. When the morphological evaluation of marrow dysplasia and cytogenetics can not give enough informations, for diagnosis of MDS, the application of flow cytometry (FCM) for immunophenotyping in MDS will become particularly important. Multiparametric evaluation of myeloid, monocytic maturation and antigen expression pattern contribute to the identification of two or more aberrancies in MDS cases. FCM evaluation of erythroid dysplasia is particularly difficult, because of the limited availability of specific markers. By analyzing the proteins involved in cellular iron metabolism, MDS erythroid cells present an "iron-loaded" phenotype characterized by increased ferritin contents and reduced transferrin receptor, which reflects the degree of dysplasia assessed by morphology. The proportion of CD34(+) cells increased, abnormal expression of surface antigen is also important. The application of flow cytometry in detecting dysplasia of myelodysplastic syndrome is discussed in this article.

Objective: To evaluate the evolution of paroxysmal nocturnal hemoglobinuria (PNH) clone and its clinical significance before and after immunosuppressive therapy (IST) in patients with aplastic anemia (AA)., Methods: A total of 186 patients diagnosed as AA were enrolled in this study. Among them, 55 patients were diagnosed as severe AA (SAA) and treated with cyclosporine (CsA) plus anti-thymocyte globulin (ATG), 131 were diagnosed as non SAA (NSAA) and treated with CsA alone. All patients were screened for PNH clone by flow cytometry before treatment and followed up for 18-76 months, with a median time of 22 months., Results: Positive PNH clones were detected in 10 SAA (18.9%) patients, significantly more than that of NSAA group [9 patients (7.4%), t = 5.041, P = 0.025]. The proportions of PNH clones in SAA group at 6, 12, 24 and > 24 months were 13.38%, 14.88%, 20.00% and 18.85%, respectively, also significantly higher than those of NSAA patients (5.67%, 5.31%, 5.47% and 9.08%, all P values < 0.05). Clinical response rates were comparable in both ATG+CsA or CsA alone groups no matter PNH clone was positive or negative., Conclusions: PNH clone are detectable in AA patients either treated with ATG plus CsA or CsA alone, and more significant by ATG plus CsA. Whether PNH clone occurred before or after IST does not affect the therapeutic efficacy.

This study was aimed to analyze the survival status of patients with diffuse large B-cell lymphoma (DLBCL) and to investigate the influence of autologous hematopoietic stem cell transplantation (auto-HSCT), different pathological types, International Prognosis Idex (IPI) on prognosis. One hundred and sixteen cases of DLBCL were analyzed retrospectively. The treatment efficacy of R-CHOP alone and R-CHOP combined with auto-HSCT as well as the influence of different immunopathologic types, IPI, hypersensitive C-reactive protein (HSCRP), α-hydroxybutyric acid deaminase (HBDH) on the prognosis of DLBCL patients including overall survival (OS) rate, progression-free survival (PFS) rate were analyzed. The results indicated that the 5-year OS for all patients was 72.4%. in which 30 patients with Ann Arbor staging III-IV received auto-HSCT plus R-CHOP. The prognosis of the 30 patients was better than that of 86 cases received R-CHOP chemotherapy alone (5-year OS was 82.5% vs 69.0%, 5-year PFS was 77.1% vs 68.3%) (P < 0.05). The prognosis of patients in germinal center B-cell-like group (GCB group) was better than that of patients in activated B-cell-like group (ABC group). Some clinical features were associated with poor prognosis including OS and PFS, such as age, B symptoms, IPI scores, the level of LDH, HSCRP and HBDH (P < 0.05) in which the level of LDH, age ≥ 60 years and B symptoms were independent prognostic factors in DLBCL patients (P < 0.05). It is concluded that auto-HSCT combined with R-CHOP can improve the long-term survival of DLBCL patients. The prognosis of patients in GCB group is better than that of patients in the ABC group. The clinical features such as age, B symptoms, IPI scores and LDH are associated with prognosis.

Objective: To explore the proportion of Th22 cells in peripheral blood of patients with aplastic anemia (AA) and evaluate its significance., Methods: From January 2011 to June 2012, a total of 47 AA patients were recruited and divided into 4 groups: severe aplastic anemia (SAA) pre-therapy (group A, n = 11), non-severe aplastic anemia (NSAA) pre-therapy (group B, n = 12), SAA post-therapy (group C, n = 12), NSAA post-therapy (group D, n = 12) and healthy donor controls (n = 12). The proportion of Th22 cells in peripheral blood of each group was evaluated by flow cytometry. The cytokines interleukin-22 (IL-22), transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured by ELISA. And the level of IL-22 mRNA was examined by reverse transcription-PCR (RT-PCR)., Results: The percentage of Th22 cells and the level of IL-22, TNF-α, IL-6 and IL-22 mRNA in group A (4.3% ± 1.4%, (57 ± 17) ng/L, (497 ± 123) ng/L, (323 ± 88) ng/L, 1.65 ± 0.51) and group C (2.6% ± 0.6%, (34 ± 10) ng/L, (314 ± 79) ng/L, (187 ± 45) ng/L, 0.92 ± 0.28) were significantly higher than that in control group (1.2% ± 0.3%, (19 ± 6) ng/L, (228 ± 50) ng/L, (134 ± 26) ng/L, 0.47 ± 0.09,all P < 0.05). The percentage of Th22 cells and the level of IL-22, TNF-α , IL-6 and IL-22 mRNA in group A were higher than those in group C (all P < 0.05). NSAA patients had similar results. The percentage of Th22 cells and the level of IL-22, TNF-α , IL-6 and IL-22 mRNA in group A were higher than those in group B (all P < 0.05). But the level of TGF-β in groups A and C were significantly lower than that in control group ((3.4 ± 1.1) and (5.8 ± 1.7) vs (9.7 ± 2.8) ng/L, P < 0.05). And the level of TGF-β in group A was lower than that of group B (P < 0.05)., Conclusions: The number of Th22 cells is elevated in AA patients. Th22 cells may be positively correlated with the development of AA. And a higher level of TNF-α, IL-6 and a lower level of TGF-β promote the differentiation of Th22 cells.

Objective: To evaluate the possible mechanism of transcription factors B cell lymphoma 6 (Bcl-6) , forkhead/winged helix transcription factor 3 (Foxp3) and retinoic acid related orphan receptor (RORγt) in CD4(+) T cells for immuno-related hematocytopenia (IRH)., Methods: CD4(+) T cells were harvested from 40 IRH patients, 38 aplastic anemia subjects and 25 normal controls and separated by magnetic activated cell sorting (MACS). Then the expressions of transcription factors of Foxp3, RORγ and Bcl-6 in CD4(+) T cells were measured by real time fluorescent quantitative-polymerase chain reaction (QRT-PCR)., Results: Auto-antibody was detected on CD34(+) cells (67.5% (27/40) ), CD15(+) cells (65.0% (26/40)), GlyA(+) cells (75.0% (30/40) ), auto-antibody involving three, two or one myeloid cell were detected in 27.5% (11/40), 52.5% (21/40), 20.0% (8/40) of IRH patients. Compensatory increase of Foxp3 mRNA was found in IRH (0.124 (0.073-0.198) vs 0.071 (0.046-0.118), P < 0.05). The expression of Bcl-6 was higher (2.243 (0.854-4.544) vs 1.211 (0.131-2.816), P < 0.05). Compared to aplastic anemia, the expression of RORγt was lower in IRH (0.133 (0.068-0.189) vs 0.290 (0.138-0.480), P < 0.01) and the ratio of Treg/Th17 shifted to Th17 in patients with aplastic anemia (Foxp3/RORγt ratio,0.500 (0.240-0.795) vs 0.975 (0.483-1.416), P < 0.01)., Conclusion: As one kind of bone marrow failures caused by autoantibody to bone marrow cells, IRH may occur due to a high expression of Bcl-6 in CD4(+) T cells, its immunopathogenesis is different from that of aplastic anemia.

Objective: To explore efficacy of imatinib for patients with chronic myeloid leukemia(CML) and its resistance-related factors during the treatment., Methods: The clinical data of 214 CML patients received imatinib were analyzed respectively in our hospital from April 2005 to December 2010. The therapy history and efficacy of regular follow-up and factors influencing drug resistance were analyzed. COX regression analysis was used to perform the univariate and multivariate analysis., Results: Until the end of follow up, thirty-one patients (14.5%) occurred drug resistance. One of them was in accelerated phase(AP), and two in blast phase(BP); 69.2% of patients achieved a complete cytogenetic response(CCyR), and 31.3% of patients achieved a major molecular response(MMR). COX analysis was performed in 207 chronic phase(CP) patients. Univariate analysis showed that the course of disease before treatment, the hemoglobin count, the white blood cell count, whether achieved CCyR or not and whether achieved MMR or not were the influencing factors for imatinib resistance. Multivariate analysis showed that whether achieved CCyR or not was the independent factor for drug resistance., Conclusion: Whether achieved CCyR or not is an independent factor and also a protective factor for imatinib resistance in patients with CML.

Aplastic anemia (AA) is a bone marrow failure disease caused by abnormal activation of T lymphocytes, resulting in the apoptosis of hematopoietic cells and bone marrow failure. Currently, hematopoietic stem cell transplantation (HSCT), immunosuppressive - therapy (IST), and supportive care (e.g. transfusion adjuvant therapy, hematopoietic growth factors, and prevention of infection) are the main treatments of AA. Granulocyte transfusion has recently been accepted as an useful adjuvant therapy of HSCT and intensive IST. This article reported a severe AA patient who failed to respond to IST, but achieved spontaneous remission three times after granulocyte transfusions from related donors. Such cases have rarely been reported. Existence of human leukocyte antigen (HLA) cross between the patient and his relatives may influence the T cell-mediated immunity, which might explain this patient's recovery.