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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).)

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.

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.

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 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.)

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: 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.

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 evaluate the efficacy and prognostic factors of autologous hematopoietic stem cell transplantation (ASCT) in multiple myeloma (MM) patients., Methods: Retrospective analysis was performed in 27 MM patients undergoing ASCT at our hospital from May 2004 to August 2011. After comparing with 28 patients achieving very good partial response (VGPR) or better outcome and not undergoing ASCT, the impact on the extent of response, progression-free survival (PFS) and overall survival (OS) as well as related prognostic factors of MM patients were analyzed., Results: All patients successfully underwent hematopoietic reconstruction without transplantation-related mortality. The complete remission (CR) rate of ASCT group increased from 25.9% (7/27) at pre-ASCT to 70.4% (19/27) at post-ASCT (P < 0.01). The estimated 5-year rate of progression-free survival was 56.2% (median not reached) in the ASCT group and 24.9% (median 29 months) in the non-ASCT group (P < 0.05). The 5-year probability of overall survival was 52.2% (median not reached) in the ASCT group and 33.1% (median 60 months) in the non-ASCT group (P > 0.05). Univariate analysis in ASCT group demonstrated that maintenance/consolidation therapy was associated with PFS (P = 0.010) and OS (P = 0.008).Patients on induction therapy containing bortezomib and early ASCT maintenance therapy all survived without disease progression until final follow-up (P = 0.010)., Conclusions: ASCT can further increase the CR rate, prolong PFS and probably OS. The incorporation of novel agents into induction, consolidation and maintenance phases has optimized the anti-myeloma activity of ASCT and may be important for improved long-term outcomes.

Objective: To evaluate the efficacies and toxicity of HAG (HHT + Ara-C + G-CSF) regimen in patients with high-risk myelodysplastic syndromes (MDS)., Methods: A total of 97 patients with high-risk MDS received HAG regimen as the induction therapy., Results: The complete remission (CR) rate of all the patients was 52.3% (45/86). The overall response (OR) rate was 66.3% (57/86). The early mortality rate was 9.3% (9/97). There was no significant difference in CR rate and OR rate between the patients aged ≥ 60 and those < 60. The OR rate was 29/34, 9/12 and 6/13 in patients with favorable karyotype, intermediate karyotype and unfavorable karyotype respectively. The OR rate was higher in patients with favorable karyotype than those with unfavorable karyotype (P = 0.038). The major adverse effect was infection., Conclusion: HAG regimen provides higher CR rate and OR rate for patients with high-risk MDS.

Objectives: To evaluate the antihypertensive effect of Xinjiang red raspberry fruit ethyl acetate extract (EER) on spontaneously hypertensive rats (SHR) and its possible mechanism from antioxidant perspective., Materials and Methods: The SHR rats were randomly divided into 3 groups, and treated with EER low dose (EERL, 100 mg/kg/d), high dose (EERH, 200 mg/kg/d), and water (SHR) through gastric gavage daily for 5 weeks. Another 8 age-matched male Wistar-Kyoto rats were used as normotensive group (WKY). The systolic blood pressure (SBP) was measured by noninvasive tail-cuff method once a week. At the end of the treatment, blood samples were collected and serum concentrations of nitric oxide (NO), superoxide dismutase (SOD), malondialchehyche (MDA), and plasma endothelin (ET) were determined., Results: Treatment of SHR rats with EER lowered the blood pressure compared with that treated with water (SHR), and the high dose showed more significant reduction in blood pressure. Treatment of SHR rats with EER increased serum NO and SOD levels and lowered ET and MDA levels. As compared with control group, NO levels were increased significantly in EERL (P < 0.01), SOD was elevated more significantly in both EERL and EERH (P < 0.01); MDA was decreased significantly in EERH group (P < 0.05), whereas plasma ET decreased more significantly in the EERH group (P < 0.05)., Conclusions: The red raspberry extracts demonstrated a dose-dependent antihypertensive effects in SHR and this may be related to increased NO activation and improved vascular endothelial dysfunction via antioxidation. These results confirmed that raspberries rich in polyphenols have potential cardiovascular protective effects.

Multi-photon absorption and excitation properties of CdSe quantum dots in hexane with different dot-sizes have been investigated. The two- and three-photon absorption (2PA and 3PA) coefficients were measured by using ~160-fs laser pulses at wavelengths of ~775-nm and ~1300-nm, respectively. The dependence of one-, two- and three-photon induced fluorescence spectra as well as their double-exponential decay on the dot-sizes was studied. Based on the fluorescence emission spectra and temporal decay constants for a given sample solution excited by one-, two-and three-photon absorption, it can be concluded that the transition pathways for fluorescence emission and decay under one-, two- and three-photon excitation are nearly identical. The optical power limiting capabilities based on 2PA and 3PA mechanisms are demonstrated separately. In addition, a saturation behavior of 3PA at ~1300 nm was observed.

This paper reports on cooperative enhancement of three-photon absorption (3PA) cross section, studied by nonlinear transmission method, in going from a one-branched to a three-branched and then to a dendritic structure. Experimentally, we observe a 72% enhanced 3PA cross-section value in going from the one-branched chromophore to the dendritic chromophore, and a 49% enhanced 3PA cross-section value in going from the one-branched chromophore to the three-branched chromophore, when the 3PA cross-section values are normalized per structure unit. Quantum chemical calculation for the one- and three-branched structures, using the cubic response (CR) theory applied to a single determinant self-consistent field (SCF) reference state, also predicts such an enhancement. Two-dimensional pi-delocalization, resulting in extended charge-transfer network in the case of the multibranched structures, is the main cause of the cooperative enhancement. Owing to the increased 3PA cross-section value for the dendritic chromophore, improved optical limiting performance at an optical communication wavelength of 1310 nm was observed, compared with the one-branched (or three-branched) chromophore, using comparable structure-unit-based concentrations. Optical stabilization capability of the dendritic chromophore was also observed at this wavelength.

Rationale and Objectives: The objective of this study is to develop and characterize new microbubbles based on lipids and sulfur hexafluoride (SF6) for targeting thrombi as an improved ultrasound contrast agent., Materials and Methods: Bioconjugate ligands were inserted into the lipid-coated membranes of SF6 gas microbubbles, and their physicochemical properties were determined. Diagnostic efficacies of SF6-filled microbubbles and the contrast agent SonoVue (Bracco Imaging, Geneve, Switzerland) were compared in dogs., Results: Suspensions of lyophilized powder were reconstituted by injecting saline containing 3.1 x 10(8) SF6 microbubbles/mL with a mean diameter of 4.4 microm. More than 90% of microbubbles had diameters between 1 and 10 microm. After reconstitution, echogenicity and microbubble characteristics were unchanged for 8 hours. Targeted microbubbles increased the echogenicity of thrombi significantly and provided a longer period of optimal signal enhancement compared with nontargeted microbubbles., Conclusions: Our thrombus-targeting microbubble contrast agent shows high echogenicity and stability and thereby enhances the visualization of intravascular thrombi and prolongs the duration of the diagnostic window.

Highly effective optical power-limiting and optical-stabilization performances have been achieved in a new type of two-photon absorbing medium. That is a liquid-dye salt system, trans-4-[p-(N,N-dimethoxyethylamino)styryl]-N-3,6,9-trioxadecylpyridinium tetrafluoroborate (abbreviated as ASDPT), which features an unusually high molar concentration (-1 M) of two-photon absorbing chromophores and the capability of withstanding a higher pulsed laser power and energy. The nonlinear transmission property and output-input characteristics were studied based on a 1-cm-long liquid-dye salt sample by use of nanosecond 1064-nm laser pulses with a repetition rate variable from 1 to 10 Hz. A superior optical-stabilization behavior of the studied material was demonstrated; the relative fluctuation of the nanosecond laser pulses can be reduced by more than two times simply by passing them through this highly concentrated nonlinear absorbing medium.

Background: Myelodysplastic syndromes (MDSs), also called preleukemias, are a group of myeloid hematopoietic malignant disorders. We studied the transformation of MDS into acute myeloid leukemia (AML)., Methods: Leukemic transformation in 151 patients with MDS was dynamically followed up. The clinical manifestation, peripheral blood and bone marrow condition, karyotypes, immunophenotypes, response to treatment, and prognosis of AML evolution from MDS (MDS-AML) were also observed., Results: During the course of this study, over the past eight years and seven months, 21 (13.91%) of 151 MDS patients progressed to overt leukemia, with a median interval of 5 (1 - 23) months. There were no significant differences between rates of leukemic transformation in comparison with the refractory anemia (RA), RA with excess of blasts (RAEB), and RAEB in transformation (RAEB-t) patient groups. Transformation occurred either gradually or rapidly. There were five parameters positively correlated to leukemic transformation: under 40 years of age, pancytopenia of 3 lineages, more than 15% blasts in the bone marrow, at least two abnormal karyotypes, and treatment with combined chemotherapy. All of the 21 patients with leukemia suffered from MDS-AML, and most of them were M2, M4, or M5. Two (9.52%) MDS-AML patients developed extramedullary infiltration. Leukopenia was found in 47.62% of these patients. Two thirds of these patients, whose bone marrows were generally hypercellular, suffered from neutropenia. After developing AML, 8 (47.06%) patients developed abnormal karyotypes. High expression of immature myeloid antigens, including CD33 [(49.83 +/- 24.50)%], CD13 [(36.38 +/- 33.84)%], monocytic antigen CD14 [(38.50 +/- 24.60)%], and stem cell marker CD34 [(34.67 +/- 30.59)%], were found on bone marrow mononuclear cells from MDS-AML patients after leukemic transformation. In some cases, lymphoid antigens, such as CD5, CD7, CD9, and CD19, coexisted with myeloid antigens. A low complete remission rate (31.25%) and a short survival time, with median survival of 6 (1 - 28) months, were found in patients with MDS-AML treated by induction chemotherapy., Conclusions: MDS has a high risk of developing into AML, either gradually or rapidly. Patients with MDS-AML have specific biological characteristics and a worse prognosis.

Background: Polycythemia vera (PV) is a malignant disorder of hemaopoietic stem cells which is characterized by clonal hyperproliferation and a low rate of apoptosis. This study was to assess endogenous erythroid colony (EEC) formation in the bone marrow of PV patients and determine its clinical significance., Methods: The bone marrow mononuclear cells of 26 patients with PV, 2 patients with secondary erythrocytosis (SE), and 19 normal controls were cultured by Marsh's method for EEC evaluation, and the clinical significance was evaluated., Results: EECs appeared in 25 patients with PV but not in 2 patients with SE and 19 normal controls. The number of EECs and the EEC ratio [EEC/erythropoietin (EPO)-dependent colony forming unit-erythroid (CFU-E)] in PV patients positively correlated with hemoglobin (Hb) levels. Their EEC number did not correlate with white blood cell (WBC) counts, platelet (PLT) counts, or leukocyte alkaline phosphatase (LAP) scores. Their EEC did not correlate with serum EPO levels. Fifteen patients with PV were treated with hydroxyurea (Hu) and/or interferon-alpha (IFN-alpha). Their EEC ratio before treatment positively correlated with the treatment time required for complete remission (CR) and negatively correlated with the time before relapse. The EEC numbers of 7 PV patients treated with Hu/IFN-alpha decreased after the blood cell counts dropped to normal levels. There was a positive correlation between the EEC ratio and the incidence of attacks of vascular thrombosis in PV patients. The numbers of apoptosised bone marrow mononuclear cells in PV patients were lower than those in normal controls. The EEC numbers of PV patients negatively correlated with the rate of apoptosis of bone marrow mononuclear cells., Conclusions: EEC formation is characteristic in PV patients. EEC number in PV patients positively correlates with Hb levels, the time required for CR, and the incidence of attacks of vascular thrombosis. EEC number negatively correlates with the time before relapse. Bone marrow suppressive treatment might decrease EEC number. Thus, EEC number is a sensitive and specific parameter reflecting the abnormal hematopoietic clone burden induced by polycythemia vera. EEC number is an important diagnostic parameter for PV patients.

Multiphoton processes, predicted theoretically in 1931, were for a long time considered to be mainly of academic interest. This view changed when it was shown that a two-photon absorption process could, because of a quadratic dependence of excitation on intensity, produce a spatially confined excitation useful for three-dimensional data storage and imaging. Two-photon absorption has received considerable attention recently because of the development of highly efficient two-photon-sensitive materials, leading to numerous technological applications. These successes have created interest in exploring applications based on three-photon excitations. For a three-photon process, a longer excitation wavelength such as those common in optical communications can be used. Also, the cubic dependence of the three-photon process on the input light intensity provides a stronger spatial confinement, so that a higher contrast in imaging can be obtained. Here we report the observation of a highly directional and up-converted stimulated emission as an amplified spontaneous emission, produced in an organic chromophore solution by a strong simultaneous three-photon absorption at 1.3 microm. This achievement suggests opportunities for a three-photon process in frequency-upconversion lasing, short-pulse optical communications, and the emerging field of biophotonics.

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 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.

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.

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.

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 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.

A two-dimensional permanent transmission grating was formed on a novel polymer-gel composite film by ultrashort ( approximately 0.5-ps) and visible ( approximately 602-nm) pulsed laser radiation. With an arrangement of three noncoplanar coherent laser beams, we used two approaches to produce direct formation of a two-dimensional grating on the film. One approach is to expose the sample twice to different combinations of two beams, and the other is to expose the sample to three laser beams simultaneously. The diffraction patterns and the relative intensity distributions for different order diffraction of the two-dimensional gratings formed on the poly-p-phenylene vinylene/V(2)O(5)-gel films are analyzed for the different two-beam combinations and relative orientations among the three laser beams. The total diffraction efficiency for the incident probe laser beam into all the non-zero-order diffraction beams reaches 48%.

To investigate the molecular basis for the distinct neuronopathic phenotypes of Gaucher disease, acid beta-glucosidases expressed from mutant DNAs in Gaucher disease type 2 (acute) and type 3 (subacute) patients were characterized in fibroblasts and with the baculovirus expression system in insect cells. Expression of the mutant DNA encoding a proline-for-leucine substitution at amino acid 444 (L444P) resulted in a catalytically defective, unstable acid beta-glucosidase in either fibroblasts from L444P/L444P homozygotes or in insect cells. This mutation was found to be homoallelic in subacute neuronopathic (type 3) Gaucher disease. In comparison, expression of the mutant cDNA encoding an arginine-for-proline substitution at amino acid 415 (P415R) resulted in an inactive and unstable protein in insect cells. This allele was found only in a type 2 patient with the L444P/P415R genotype. The substantial variation in the type 3 phenotype (L444P homozygotes) suggests the complex nature of the molecular basis of phenotypic variation in Gaucher disease. Yet, the association of neuronopathic phenotypes with alleles producing severely compromised (L444P) or functionally null (P415R) enzymes indicates that the effective level of residual activity at the lysosome is likely to be a major determinant of the severity of Gaucher disease.