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Background：Downregulation of CD20, a molecular target for monoclonal antibodies (mAbs), is a clinical problem leading to decreased efficacy of anti-CD20-based therapeutic regimens.Up to one-third of diffuse large B cell lymphoma (DLBCL) patients eventually develop resistance to R-CHOP regimen, since the remaining therapeutic options are limited. LW-213, a derivative of wogonin, is reported to possess antineoplastic properties in a variety of cancers, but whether it has effects on DLBCL is n-ot known. Studies have reported that upregulation of CD20 expression b-y either HDACi or silenced SOX2 expression showed sensitizing potential in Rituximab-induced cell death in malignant B cells. Our study was to explore whether LW-213 could sensitize DLBCL to Rixutimab thus improve therapeutic efficacy. Methods： Two DLBCL cell lines, RI-1 (ABC subtype) and Su-DHL -8 (GCB subtype), were used in our study. RI-1 and Su-DHL-8 cells were treated with LW-213 at different doses and for different times, and their proliferation and viability were detected by Cell counting kit-8 (CCK8).Flow cytometry was used to determine surface CD20 expression. Western blotting and q-PCR were applied to examine the protein and mRNA levels of CD20, SOX2, Ace-H3 and Ace-H3K27. CDC assay was used to evaluate the synergistic effects of LW-213 and Rixutimab. Results：We showed that LW-213 inhibited the proliferation of human DLBCL cell lines (Su-DHL-8、RI-1 ) in dose-and time-dependent manners with IC 50 values at the low μmol/L levels, meanwhile it potently inhibited primary lymphoma cells derived from peripheral blood of B-cel-l lymphoma patients. Furthermore, LW-213 significantly increased CD20 surface expression and the acetylation level of histone in DLBCL cell li-nes. Inversely，the SOX2 expression level remarkably decreased. Finally,Combination with LW-213 significantly synergized Rituximab-induced cell death in vitro. Conclusion： The results demonstrate that LW-213 sensitizes DLBCL cells to Rituximab in vitro by upregulating CD20 expression and the SOX2/ace-H3K27/ace-H3 axis may plays a critical role in CD20 upregulation processing. Even though this strategy is important in vitro models,the upregulating CD20 expression therapy against DLBCL proposed in this study warrants further study in vivo and clinical trials . Keywords：CD20 DLBCL Rituximab SOX2 Histone Deacetylation Disclosures No relevant conflicts of interest to declare. more...

Hepatitis B virus (HBV) is a hepatotropic and a lymphotropic virus. An association between HBV and hematologic malignancies has been determined previously; however, the association between HBV infection and multiple myeloma (MM) remains controversial. The present study aimed to assess the prevalence of HBV infection in patients with MM, and investigate their characteristics and prognostic significance. The clinical data of 165 patients with MM who had received at least four cycles of chemotherapy between April 2008 and February 2017 at Nanjing Drum Tower Hospital (Nanjing, China) were collected. HBV markers were determined using ELISA. The rates of acute or chronic HBV infection and resolved HBV infection in patients with MM were 12.12 and 26.06%, respectively. The gain of 1q21 was significantly more prevalent in the patients who were classified as HBV-positive compared with the patients who were classified as HBV-negative (54 vs. 38.2%; P=0.048), and the level of alanine transaminase in patients who were classified as HBV-positive was significantly increased compared with the non-infected group (63.29 vs. 24.66 U/l; P=0.043). Lactate dehydrogenase, serum creatinine and serum calcium levels were additionally determined to be significant risk factors of overall survival. The progression-free survival (PFS) of patients who were classified as HBV-positive was decreased compared with patients who were classified as HBV-negative (18.97 vs. 29.67 months; P=0.006), and being HBV-positive was determined to be an independent prognostic factor of PFS. HBV infection may contribute to MM progression through 1q21 amplification, and improved monitoring of HBV markers in patients with MM may be required. more...

Cutaneous T-cell lymphomas (CTCLs) represent a rare form of non-Hodgkin lymphomas characterized by an accumulation of malignant CD4+ T cells in the skin. TP53 genetic alteration is one of the most prevalent genetic abnormalities in CTCLs. Therefore, it is a promising target for innovative therapeutic approaches. We found that p53 could physically interact with histone deacetylase (HDAC) 1 and HDAC8, and was subsequently deacetylated to lose its function in CTCL cells, and the p53 downstream apoptosis-associated genes were repressed. Thus, the anti-CTCL activity displayed by HDAC inhibitors depends on p53 status. However, recent studies have reported that HDAC inhibitors could induce a wide variety of drug-resistant characteristics in cancer cells by regulating ATP-binding cassette transporters. Moreover, we discovered that Baicalein, a natural product, exhibited an inhibitory effect on HDAC1 and HDAC8. Though the inhibition of HDAC1 was mild, Baicalein could induce the degradation of HDAC1 through the ubiquitin proteasome pathway, thereby markedly upregulating the acetylation of histone H3 without promoting ATP-binding cassette transporter gene expression. In terms of the mechanism, Baicalein showed better growth inhibition than traditional HDAC inhibitors in CTCLs. This study indicates a special mechanism of HDAC1 and HDAC8 and p53 in T-cell lymphoma cells and identifies a potential and safe natural HDAC inhibitor for the treatment of CTCLs. more...

T-cell malignancies are characterized by the excessive proliferation of hematopoietic precursor cells of T-cell lineage lymphocytes in the bone marrow. Previous studies suggest that T-cell malignancies are usually accompanied by highly activated PI3K/AKT signaling which confers the ability of cancer cells to proliferate and survive. Here, we found that GL-V9, a newly synthesized flavonoid compound, had a potent to inhibit the activation of AKT1 and induce the cell apoptosis in T-cell malignancies including cell lines and primary lymphoblastic leukemia. Results showed that GL-V9-induced degradation of AKT1 blocked PI3K/AKT1 signaling and the degradation of AKT1 could be reversed by NH4Cl, an inhibitor of lysosomal function. Inhibiting AKT1 promoted dephosphorylation of FOXO3A and its nuclear translocation. We further demonstrated that GL-V9-induced apoptosis effects were dependent on the binding of FOXO3A to the BIM promoter, resulting in the production of BH3-only protein BIM. Moreover, GL-V9 showed a more persistent and stronger apoptosis induction effects than pharmacologic PI3K inhibitor. The in vivo studies also verified that GL-V9 possessed the anti-tumor effects by reducing the leukemic burden in T-ALL-bearing BALB/c nude mice. In conclusion, our study provides a new insight into the mechanism of GL-V9-induced apoptosis, suggesting the potency of GL-V9 to be a promising agent against T-cell malignancies. more...

Many model based image reconstruction (MBIR) methods for x-ray CT are formulated as convex minimization problems. If the objective function is nonsmooth. primal-dual algorithms are applicable with the drawback that there is an increased memory cost due to the dual variables. Some algorithms recently developed for large-scale nonsmooth convex programs use adaptive smoothing techniques and are of the primal type. That is, they achieve convergence without introducing the dual variables, hence without the increased memory. We discuss one such algorithm with an O(1/k) convergence rate, where k is the iteration number. We then present an extension of it to handle strong convex objective functions. This new algorithm has the optimal convergence rate of O(1/k 2) for its problem class. Our preliminary numerical studies demonstrate competitive performance with respect to an alternative method. more...

// Jing Wang 1, * , Min Zhou 1, * , Qi-Guo Zhang 1, * , Jingyan Xu 1, * , Tong Lin 1 , Rong-Fu Zhou 1 , Juan Li 1 , Yong-Gong Yang 1 , Bing Chen 1 , Jian Ouyang 1 1 Department of Hematology, The Affiliated DrumTower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu, PR China * These authors contributed equally to this work and should be considered as co-first authors Correspondence to: Jian Ouyang, email: ouyang211@hotmail.com Bing Chen, email: chenbing2004@126.com Keywords: diffuse large B-cell lymphoma, p65, NF-κB, international prognostic index Received: July 25, 2016 Accepted: November 22, 2016 Published: December 26, 2016 ABSTRACT Purpose: We estimated the expression of nuclear factor kappa B/p65 in non-germinal center B-cell-like subtype diffuse large B-cell lymphoma, to investigate its relationship to clinicopathological features, and to further evaluate its prognostic value and clarify its impact on survival. Results: Among the 49 patients enrolled in this study, 14 (28.6%) had positive p65 expression. The negative p65 group had significantly better survival compared to the positive p65 group in terms of both the 3-year estimated OS (91.2% vs. 39.3%, p = 0.003) and PFS (75.6% vs. 26.5%, p = 0.002). In patients with 4 or more risk factors, p65 was an independent prognostic factor of OS (HR 5.99, 95%CI=1.39-25.75, p=0.016) and PFS (HR 4.01, 95%CI=1.15-14.00, p=0.029). Materials and Methods: The expression of the NF-κB/p65 protein was deteremined by immunohistochemistry in 49 non-GCB DLBCL. Survival was assessed by the Kaplan–Meier method and Cox multivariate analysis. The median patient follow-up period was 24 months. Conclusions: The expression of NF-κB/p65 has prognostic value in high risk non-GCB DLBCL, and it is a suitable target for the development of new therapies. more...

We present a facile one-pot approach to fabricate tough TiO 2 -rGO-PDMAA nanocomposite hydrogel. Both synchronous polymerization of N, N -dimethylacrylamide (DMAA) monomer and reduction of graphene oxide (GO) sheets into porous hydrogel network are triggered by TiO 2 nanoparticles under the UV irradiation. The reduction of GO is accompanied color changes of the hydrogel from light-brown to black. The interpenetrating double hydrogel network between PDMAA chains and rGO can be fabricated at a considerable GO content, at which the hydrogel exhibits tough mechanical strength, good swelling ratio and quick self-recovery character. Benefiting from the excellent carrier mobility and large surface area of the rGO, our hydrogel has an improved photo degradation performance for methylene blue, suggesting its potential application in the wastewater treatment. more...

Background We assessed the prognostic significance of pretreatment C-reactive protein (CRP) concentration in diffuse large B-cell lymphoma (DLBCL) patients. Methods We retrospectively reviewed 156 patients with newly diagnosed DLBCL. Receiver operating characteristic (ROC) curve analysis was used to generate a cutoff value for CRP. Both log-rank test and multivariable analysis by Cox regression model were used to assess the impact of pretreatment CRP concentrations on the overall survival (OS) and progression-free survival (PFS). Results Among those 156 patients enrolled, increased CRP concentration was seen in 51 patients before treatment (≥ 20 mg/l), while the other 105 patients were considered with low CRP concentration. There was no obvious difference in the baseline characteristics between two groups. Increased CRP concentration was significantly associated with poorer OS and PFS than those patients with low CRP concentration (P = 0.001 and P = 0.000, respectively). Multivariable analysis further showed that CRP concentration was an independent predictor of OS (hazard ratio [HR] = 0.47; 95% confidence interval [CI] = 0.24–0.92, P = 0.028) and PFS (HR = 0.37; 95% CI = 0.30–0.87, P = 0.013). Conclusion CRP concentration before treatment was an independent prognostic factor in patients with DLBCL. more...

The therapeutic effects and preliminary mechanism of abandoned porphyra haitanensis polysaccharides (APHP) in diabetic mice induced by alloxan were studied in this paper. The intragastric administration of APHP for 21 days induced an obvious decrease (P more...

T-cell acute lymphoblastic leukemia (T-ALL) results from the collaboration of multiple genetic abnormalities in the transformation of T-cell progenitors. Plant homeodomain finger protein 6 (PHF6) has recently been established as a key tumor suppressor, which is mutated in T-ALL; however, the clinical significance of PHF6 mutations has not been fully determined in adult T-ALL. In the present study, amplification of the PHF6 exons was performed, followed by DNA sequencing to identify the genomic mutations and examine the expression of PHF6 in adult patients with T-ALL. The correlation between PHF6 mutations and clinical features was also analyzed using a χ2 test, and between PHF6 mutations and survival curve using the Kaplan-Meier methods. PHF6 mutations were detected in 27.1% of the Chinese adults with T-ALL (16/59), 10 of which were found to be novel mutations. A significantly lower expression level of PHF6 was observed in T-ALL patients with PHF6 mutations compared with those without mutations. Of the observed mutations in PHF6, 6/16 were frame-shift mutations, indicating a PHF6 dysfunction in those patients. Of note, PHF6 mutations were found to be significantly associated with older age, lower hemoglobin levels, higher frequency of CD13 positivity and higher incidence of splenomegaly or lymphadenopathy. Furthermore, PHF6 mutations were found to be significantly correlated with Notch homolog 1, translocation-associated (Drosophila) (NOTCH1) mutations. The patients with T-ALL with co-existence of the two mutations had a significantly shorter event-free survival and a poor prognosis. The present results indicated that PHF6 is inactivated in adult T-ALL, due to its low expression and mutations. The present data indicated the synergistic effect of PHF6 and NOTCH1 mutations, as well as their co-existence, on the oncogenesis of adult T-ALL, and their potential as a prognostic marker for the disease. more...

AML1/ETO fusion gene is one of disease-causing genes of t(8;21)-positive acute myeloid leukemia (AML). Oroxylin A (OA) has showed anticancer effects on other cancer cells. Here, studies were conducted to determine the antileukemia effect of OA on t(8;21)-positive AML cells in vitro and in vivo.The effects of OA on cell viability of t(8;21)-positive Kasumi-1 and primary AML cells were analyzed by MTT assay. Cell differentiation was examined by NBT reduction assay, flow cytometry analysis for CD11b/CD14, and Giemsa stain. Protein expressions were determined by Western blots. Immunofluorescence assay was used to verify the effect of OA on HDAC-1 expression in vivo. Immunohistochemical staining was applied to evaluate leukemic infiltration of AML-bearing NOD/SCID mice.OA enhanced NBT reduction activity and CD11b/CD14 expression of AML1/ETO-positive AML cells markedly. Results of Giemsa staining also demonstrated that OA could induce the morphologic changes with reduction of nuclear/cytoplasmic ratios, suggesting the cell differentiation induced by OA. Further study showed that OA decreased the expression of fusion protein AML1/ETO and down-regulated HDAC-1 protein levels in vitro and in vivo. Moreover, OA increased the expression of differentiation-related proteins C/EBPα and P21. Acetylation levels of histones were also advanced obviously after treatment of OA. In vivo study indicated that OA could prolong the survival of AML-bearing NOD/SCID mice and reduce leukocytic infiltration of the spleen.All these results suggested that OA might be a novel candidate agent for differentiation therapy for AML1/ETO-positive AML and the mechanism required further investigation. more...

Introduction There is currently no optimal treatment modality for refractory or relapsed Extranodal NK/T-cell lymphoma, nasal type (ENKTL). In recent years, programmed cell death protein 1 (PD-1)/programmed cell - ligand 1 pathway blockade and histone deacetylase inhibitors have emerged as promising strategies for refractory or relapsed ENKTL. Accumulating evidence has shown that therapeutic effects of anti-PD-1 antibody could be enhanced by histone deacetylase inhibitors. Patient concerns A 52-year-old male patient was diagnosed with stage I ENKTL by biopsy on February 2010. Diagnosis positron emission tomography-computed tomography (PET-CT) and biopsy were used to diagnose relapsed ENKTL in 2014. Interventions The patient was treated with radiotherapy and six cycles of etoposide, prednisone, vincristine (Oncovin), cyclophosphamide and doxorubicin hydrochloride and achieved complete remission (CR) by PET-CT in August 2010. In November 2014, the patient was diagnosed with relapsed stage IV ENKTL and was treated with six cycles of alternative chemotherapy with the regimen of steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide and pegaspargase plus Gemcitabine, Oxaliplatin along with radiotherapy. The patient achieved remission and was placed on thalidomide maintenance treatment. Upon suspicion of relapse suggested by PET-CT, Autologous stem cell transplant was performed after BCNU, etoposide, Ara-C, and melphalan preconditioning on February 2016. Following relapse again in December 2016, the lesions of left femur were treated with radiotherapy and he received anti-PD-1 antibody. He was treated with 4 cycles of pegaspargase plus Gemcitabine, Oxaliplatin on August 2017. The patient's condition improved. He received maintenance and consolidation therapy including lenalidomide, radiotherapy of the right nasal cavity and paranasal sinuses and antigen-specific reactive T cell infusions. PET-CT imaging showed there was high metabolic activity signal in the distal end of right femoral on August 2018 and the treatment regimen was adjusted to radiotherapy of the distal end of right femoral and systemic treatment of PD-1 antibody Sintilimab and chidamide 30 mg. After 5 months post-treatment, biopsy of nasopharynx showed no lymphoma cells. The patient continued the treatment of Sintilimab and chidamide 20 mg. Outcomes PET-CT imaging showed his lesions obtained remission after 8 months post-treatment. Conclusion Thus, combination of sintilimab and chidamide can be used to treat relapsed ENKTL following treatment failure from chemo-, radio-, and immuno-therapy. A clinical trial has been launched. more...

Importance Several antifungal drugs are available for antifungal prophylaxis in patients with hematological disease or who are undergoing hematopoietic stem cell transplantation (HSCT). Objective To summarize the evidence on the efficacy and adverse effects of antifungal agents using an integrated comparison. Data Sources Medline, EMBASE, and the Cochrane Central Register of Controlled Clinical Trials were searched to collect all relevant evidence published in randomized clinical trials that assessed antifungal prophylaxis in patients with hematological disease. Sources were search from inception up to October 2019. Study Selection Studies that compared any antifungal agent with a placebo, no antifungal agent, or another antifungal agent among patients with hematological disease or undergoing HSCT were included. Of 39 709 studies identified, 69 met the criteria for inclusion. Data Extraction and Synthesis The outcome from each study was estimated using the relative risk (RR) with 95% CIs. The Mantel–Haenszel random-effects model was used. The reliability and validity of the networks were estimated by addressing inconsistencies in the evidence from comparative studies of different treatments. Data were analyzed from December 2019 to February 2020. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses for Network Meta-analysis (PRISMA-NMA) guideline. Main Outcomes and Measures The primary outcomes were invasive fungal infections (IFIs) and mortality. The secondary outcomes were fungal infections, proven IFIs, invasive candidiasis, invasive aspergillosis, fungi-related death, and withdrawal owing to adverse effects of the drug. Results We identified 69 randomized clinical trials that reported comparisons of 12 treatments with at total of 14 789 patients. Posaconazole was the treatment associated with the best probability of success against IFIs (surface under the cumulative ranking curve, 86.7%; mean rank, 2.5). Posaconazole treatment was associated with a significant reduction in IFIs (RR, 0.57; 95% CI, 0.42-0.79) and invasive aspergillosis (RR, 0.36; 95% CI, 0.15-0.85) compared with placebo. Voriconazole was associated with a significant reduction in invasive candidiasis (RR, 0.15; 95% CI, 0.09-0.26) compared with placebo. However, posaconazole was associated with a higher incidence of withdrawal because of the adverse effects of the drug (surface under the cumulative ranking curve, 17.5%; mean rank, 9.2). In subgroup analyses considering efficacy and tolerance, voriconazole might be the best choice for patients undergoing HSCT, especially allogenic HSCT; however, posaconazole was ranked as the best choice for patients with acute myeloid leukemia or myelodysplastic syndrome. Conclusions and Relevance These findings suggest that voriconazole may be the best prophylaxis option for patients undergoing HSCT, and posaconazole may be the best prophylaxis option for patients with acute myeloid leukemia or myelodysplastic syndrome. more...

Objective. To investigate the rule of kidney-tonifying method in Chinese medicine for the treatment of bone marrow suppression (BMS), in order to provide evidence and references for the clinical application of herbs and formulae. Design. Collecting and sorting the information about the treatment of BMS related to kidney-tonifying (Bushen) method in Chinese medicine literatures on databases including Chinese National Knowledge Infrastructure (CNKI), and Chinese Biomedical Literature Database (CBM), establishing a database of BMS treating formulae after radiotherapy and chemotherapy with traditional Chinese medicine (TCM) kidney-tonifying method, and finally applying the relevant theories and techniques of data mining to analyze the medication rules of it. Results. A total of 239 formulae and 202 herbs were included in this database, in which the herbs occurred 2,602 times in general. The high frequency herbs included Astragali Radix (Huangqi), Atractylodis Macrocephalae Rhizoma (Baizhu), and Ligustri Lucidi Fructus (Nvzhenzi). The main herb categories were deficiency-tonifying herbs, blood-activating herbs, dampness-draining diuretic herbs, heat-clearing herbs, and digestant herbs. Deficiency-tonifying herbs accounted for 64.60% of the total number. A total of 8 clustering formulae are summarized according to cluster analysis and 26 herb suits association rules are identified by Apriori algorithm. Conclusion. The treatment of BMS is mainly based on the method of invigorating the spleen and tonifying the kidney and liver to strengthen healthy qi, supplementing with blood-activating herbs, and dampness-draining diuretic herbs to eliminate pathogenic factors. more...

Ensembles of nitrogen-vacancy (NV) centers in diamonds are widely utilized for magnetometry, magnetic-field imaging and magnetic-resonance detection. They have not been used for magnetometry at zero ambient field because Zeeman sublevels lose first-order sensitivity to magnetic fields as they are mixed due to crystal strain or electric fields. In this work, we realize a zero-field (ZF) magnetometer using polarization-selective microwave excitation in a 12C-enriched HPHT crystal sample. We employ circularly polarized microwaves to address specific transitions in the optically detected magnetic resonance and perform magnetometry with a noise floor of 250 pT/Hz^(1/2). This technique opens the door to practical applications of NV sensors for ZF magnetic sensing, such as ZF nuclear magnetic resonance, and investigation of magnetic fields in biological systems. more...

Low-cost and high-performance catalysts are highly desirable for the oxygen reduction reaction (ORR) in metal–air batteries. Herein, a Co3O4/N-doped Ketjenblack (Co3O4/N-KB) composite is proposed as a high performance catalyst for Al–air batteries. The synergistic effect between Co3O4 and N-KB enables the Co3O4/N-KB composite to have a much higher cathodic current, a much more positive half-wave potential and more electron transfer in comparison with Co3O4 or N-KB alone. The Co3O4/N-KB composite favors a direct four electron pathway in the ORR process, and its ORR current density even outperforms the commercial Pt/C (20 wt%). Al–air batteries using the as-prepared catalyst in the air electrode were constructed, which displayed a high discharge voltage plateau of ∼1.52 V, comparable to that of the commercial Pt/C. The developed Co3O4/N-KB composite here could meet the requirements of large-scale application of metal–air batteries due to the much cheaper cobalt source and more economically commercialized carbon source compared to the commercial Pt/C. more...

GATA-1, a zinc finger transcription factor, has been demonstrated to play a key role in the progression of leukemia. In this study, we investigate the effects of wogonoside, a naturally bioactive flavonoid derived from Scutellaria baicalensis Georgi, on cell growth and cell cycle in chronic myeloid leukemia (CML) cells, and uncover its underlying mechanisms. The experimental design comprised CML cell lines K562, imatinib-resistant K562 (K562r) cells, and primary CML cells, treated in vitro or in vivo, respectively, with wogonoside; growth and cell cycle were then evaluated. We found that wogonoside could induce growth inhibition and G0/G1 cell cycle arrest in both normal and K562r cells. Wogonoside promotes the expression of GATA-1 and facilitates the binding to methyl ethyl ketone (MEK) and p21 promoter, thus inhibiting MEK/extracellular signal-regulated kinase signaling and cell cycle checkpoint proteins, including CDK2, CDK4, cyclin A, and cyclin D1, and increasing p21 expression. Furthermore, in vivo studies showed that administration of wogonoside decreased CML cells and prolonged survival in NOD/SCID mice with CML cell xenografts. In conclusion, these results clearly revealed the inhibitory effect of wogonoside on the growth in CML cells and suggested that wogonoside may act as a promising drug for the treatment of imatinib-resistant CML. more...

Background The aim of this study was to investigate the anticancer effect and related mechanisms of gambogic acid (GA), a traditional Chinese medicine, on human leukemia cell line K562, together with the effect on bone marrow mononuclear cells (MNCs). Material and methods K562 cells and MNCs were treated with various concentrations and treatment times of GA. Inhibitory rate was detected by use of the Cell Counting Kit-8 (CCK-8) assay. Apoptosis was analyzed by morphological detection, Annexin-V/PI doubling staining, and TUNEL assays. The expression changes of pivotal proteins were evaluated by Western blotting. Results GA not only suppressed cell proliferation, but also induced apoptosis of K562 cells in a dose-dependent manner. While it did not significantly inhibit cell proliferation of MNCs, it did induce apoptosis in a dose-dependent manner. CCK-8 assay revealed that the proliferation of K562 cells was significantly inhibited when the concentration of GA was more than 0.5 μM. Morphological detection showed the nuclei became denser and more intense orange in K562 cells after GA treatment compared with the untreated group. The expression levels of BCL-2, nuclear factor-κB (NF-κB), c-myc, phosphatidylinositol3-kinase (PI3K), and phosphorylation of serine-threonine kinase (p-AKT) were down-regulated by GA. Conclusions GA significantly suppressed the proliferation of K562 cells, but has less effect on MNCs. The inhibition of K562 cells proliferation and apoptosis induced by GA might be related to the down-regulation of BCL-2, NF-κB, c-myc, PI3K, and p-AKT. more...

Based on 3D-TCAD simulations, single-event transient (SET) effects and charge collection mechanisms in fully depleted silicon-on-insulator (FDSOI) transistors are investigated. This work presents a comparison between 28-nm technology and 0.2-μm technology to analyze the impact of strike location on SET sensitivity in FDSOI devices. Simulation results show that the most SET-sensitive region in FDSOI transistors is the drain region near the gate. An in-depth analysis shows that the bipolar amplification effect in FDSOI devices is dependent on the strike locations. In addition, when the drain contact is moved toward the drain direction, the most sensitive region drifts toward the drain and collects more charge. This provides theoretical guidance for SET hardening. more...

Model based image reconstruction often includes regularizers to encourage a priori image information and stabilize the ill-posed inverse problem. Popular edge preserving regularizers often penalize the first order differences of image intensity values. In this work, we propose a hybrid regularizer that additionally penalizes the gradient of an auxiliary variable embedded in the half-quadratic reformulation of some popular edge preserving functions. As the auxiliary variable contain the gradient information, the hybrid regularizer penalizes both the first order and the second order image intensity differences, hence encourages both piecewise constant and piecewise linear image intensity values. Our experimental data using combined physical data acquisition and computer simulations demonstrate the effectiveness of the hybrid regularizer in reducing the stair-casing artifact of the TV penalty, and producing smooth intensity variations. more...

Iterative reconstruction (IR) methods for x-ray CT is a promising approach to improve image quality or reduce radiation dose to patients. The goal of this work was to use task based image quality measures and the channelized Hotelling observer (CHO) to evaluate both analytic and IR methods for clinical x-ray CT applications. We performed realistic computer simulations at five radiation dose levels, from a clinical reference low dose D0 to 25% D0. A fixed size and contrast lesion was inserted at different locations into the liver of the XCAT phantom to simulate a weak signal. The simulated data were reconstructed on a commercial CT scanner (SOMATOM Definition Flash; Siemens, Forchheim, Germany) using the vendor-provided analytic (WFBP) and IR (SAFIRE) methods. The reconstructed images were analyzed by CHOs with both rotationally symmetric (RS) and rotationally oriented (RO) channels, and with different numbers of lesion locations (5, 10, and 20) in a signal known exactly (SKE), background known exactly but variable (BKEV) detection task. The area under the receiver operating characteristic curve (AUC) was used as a summary measure to compare the IR and analytic methods; the AUC was also used as the equal performance criterion to derive the potential dose reduction factor of IR. In general, there was a good agreement in the relative AUC values of different reconstruction methods using CHOs with RS and RO channels, although the CHO with RO channels achieved higher AUCs than RS channels. The improvement of IR over analytic methods depends on the dose level. The reference dose level D0 was based on a clinical low dose protocol, lower than the standard dose due to the use of IR methods. At 75% D0, the performance improvement was statistically significant (p < 0.05). The potential dose reduction factor also depended on the detection task. For the SKE/BKEV task involving 10 lesion locations, a dose reduction of at least 25% from D0 was achieved. more...

We present a direct (noniterative) algorithm for 1-D quadratic data fitting with neighboring intensity differences penalized by the Huber function. Applications of such an algorithm include 1-D processing of medical signals, such as smoothing of tissue time concentration curves in kinetic data analysis or sinogram preprocessing, and using it as a subproblem solver for 2-D or 3-D image restoration and reconstruction. dynamic programming was used to develop the direct algorithm. The problem was reformulated as a sequence of univariate optimization problems, for ${k} =\textsf {1}, \ldots , {N}$ , where ${N}$ is the number of data points. The solution to the univariate problem at index ${k}$ is parameterized by the solution at ${k}+\textsf {1}$ , except at ${k}={N}$ . Solving the univariate optimization problem at ${k}={N}$ yields the solution to each problem in the sequence using back-tracking. Computational issues and memory cost are discussed in detail. Two numerical studies, tissue concentration curve smoothing and sinogram preprocessing for image reconstruction, are used to validate the direct algorithm and illustrate its practical applications. In the example of 1-D curve smoothing, the efficiency of the direct algorithm is compared with four iterative methods: the iterative coordinate descent, Nesterov’s accelerated gradient descent algorithm, FISTA, and an off-the-shelf second order method. The first two methods were applied to the primal problem, the others to the dual problem. The comparisons show that the direct algorithm outperforms all other methods by a significant factor, which rapidly grows with the curvature of the Huber function. The second example, sinogram preprocessing, showed that robustness and speed of the direct algorithm are maintained over a wide range of signal variations, and that noise and streaking artifacts could be reduced with almost no increase in computation time. We also outline how the proposed 1-D solver can be used for imaging applications. more...

We have significantly improved four data-driven respiratory motion (RM) extraction methods for various activity distributions in clinical myocardial perfusion (MP) and $^{\mathbf {18}}$ F-FDG PET datasets. They are activity distributions: (1) with high myocardial uptake, (2) same as (1) but with portion of the heart outside the image, and with high image intensity (3) in the liver and (4) in the lung area without attenuation compensation. In Method #1, a 3D volume-of-interest (VOI) was placed over the heart region of the PET image obtained from the total acquisition time period. The surrogate RM signals were obtained from the centroids of the image intensity of the myocardial activity uptake within the same VOI of PET images obtained from rebinned listmode data in short time intervals. The Fourier Transform (FT) of the time sequence of surrogate RM signals and smoothing reveal the RM peak and its average period, $\text{P}_{\mathbf {av}}$. In Methods #2, #3, and #4, specially-shaped 3D VOIs were placed over the heart, the top of the liver, and the bottom of the lungs, respectively. Then, the same procedures used in Method #1 were employed except using the total counts within the corresponding VOI. The location, sizes and shapes of the VOIs were optimized for the highest signal-to-noise (S/N) in the RM peak extraction. The improved RM extraction methods were evaluated using 14 patient datasets. Method #1 was shown to work well for 79% of the datasets, and Pav showing high S/N and excellent agreement (Pearson correlation coefficient 0.997) with those obtained from an external RM monitoring belt system. Method #2 was applied successfully to 14%, and Methods #3 and #4 to the rest of datasets. Excellent agreements were also found in cross comparison between the methods. We conclude that the improved data-driven RM extraction methods which showed successful results in various PET image datasets will provide an important first step for the motion compensation application in commercial PET scanners. more...

We show that two problems involving the anisotropic total variation (TV) and interval constraints on the unknown variables admit, under some conditions, a simple sequential solution. Problem 1 is a constrained TV penalized image denoising problem; problem 2 is a constrained fused lasso signal approximator. The sequential solution entails finding first the solution to the unconstrained problem, and then applying a thresholding to satisfy the constraints. If the interval constraints are uniform, this sequential solution solves problem 1. If the interval constraints furthermore contain zero, the sequential solution solves problem 2. Here uniform interval constraints refer to all unknowns being constrained to the same interval. A typical example of application is image denoising in x-ray CT, where the image intensities are non-negative as they physically represent linear attenuation coefficient in the patient body. Our results are simple yet seem unknown; we establish them using the Karush-Kuhn-Tucker conditions for constrained convex optimization. more...

The preparation of tough and healable hydrogels in one step remains a big challenge throughout the field of hydrogel methodology. Herein, we fabricated a series of Poly(N,N-dimethyl acrylamide)-TiO2-gum arabic (PDMAA-TiO2-GA) hybrid hydrogels by simply introducing nanoparticles TiO2 and vinyl-modified gum arabic (GMAGA) into polymer networks. Without complicate molecular design and post-treating process, the hydrogel molding process was simple and effective. The hydrogel exhibited highly stretchable, self-healing and tensility reinforcing performances with the optimized compositions of 30% DMAA, 0.6% GMAGA and 0.13% TiO2. The maximum elongation of the hydrogel after self-healing recover could reach nearly 700% after only 20min healing time. The hydrogel could ensure 20 times continuous compressive or tensile tests without obvious deformation. Amazing was the significantly enhanced tensile modulus from 5kPa to 40kPa after 20 stretch-release cycles. The facile preparation and fascinating tensility reinforcing performance benefit the potential application of the carbohydrate GA in hydrogels. more...

Primary bone lymphomas (PBLs) are composed of malignant lymphoid cells presenting in osseous sites, without supra-regional lymph node or extranodal involvement. We systematically characterized the immunophenotype and the myeloid differentiation factor 88 (MYD88)-L265P gene mutation status in PBL. Clinical data from 19 patients with PBL treated at Nanjing Drum Tower Hospital between 2009 and 2015 were analyzed retrospectively. Protein expression patterns were identified immunohistochemically, and MYD88 mutation was assessed using polymerase chain reaction and direct DNA sequencing. Fifteen patients presented with diffuse large B-cell lymphoma. Clinical factors favoring a good prognosis were an age < 60 years and rituximab treatment. B-cell lymphoma 2 expression was detected in 5/15 diffuse large B-cell lymphoma patients, and was associated with a poor prognosis in a univariate model. Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling factors were upregulated in PBLs. All eighteen evaluable PBL samples harbored wild-type MYD88. These data thus suggest that age and rituximab treatment are independent prognostic factors determining overall survival, and that activation of JAK/STAT3 signaling may promote the pathogenesis of PBL. Moreover, the absence of MYD88-L265P mutation in PBL indicate there are distinct pathogenetic backgrounds among extranodal lymphomas. more...

Natural killer/T cell lymphoma (NKTCL) is an aggressive and heterogeneous entity of non-Hodgkin lymphoma, strongly associated with Epstein-Barr virus (EBV) infection. To identify molecular subtypes of NKTCL based on genomic structural alterations and EBV sequences, we performed multi-omics study on 128 biopsy samples of newly diagnosed NKTCL and defined three prominent subtypes, which differ significantly in cell of origin, EBV gene expression, transcriptional signatures, and responses to asparaginase-based regimens and targeted therapy. Our findings thus identify molecular networks of EBV-associated pathogenesis and suggest potential clinical strategies on NKTCL. more...

This study aims to investigate the prognostic significance of the MYC protein expression in diffuse large B cell lymphoma (DLBCL) patients treated with RCHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone). A total of 60 patients with DLBCL from 2008 to 2013 were included. Formalin-fixed, paraffin-embedded DLBCL samples were analyzed for MYC protein expression and divided into high or low MYC group. The MYC protein expression and the international prognostic variables were evaluated. The high MYC protein expression predicted a shorter 3-year estimated overall survival (OS) and progression-free survival (PFS) versus the low MYC protein expression (57 % vs. 96 %, P < 0.001 and 50 % vs. 96 %, P = 0.001, respectively). Multivariate analysis confirmed the prognostic significance of the MYC protein expression for both OS (HR, 11.862; 95 % CI, 1.462-96.218; P = 0.021) and PFS (HR, 6.073; 95 % CI, 1.082-34.085; P = 0.040). MYC protein expression with International Prognostic Index (IPI) score distinguished patients into three risk groups with different 3-year OS rates (χ (2) 23.079; P < 0.001) and distinct 3-year PFS rates (χ (2) 15.862; P < 0.001). This study suggests that the MYC protein expression is an important inferior prognostic factor for survival in patients with DLBCL treated with RCHOP. The combinative model with IPI score and MYC protein expression could stratify DLBCL patients into prognostically relevant subgroups more effectively than either the IPI or the MYC alone. more...

The efficacy and safety of chidamide, a new subtype-selective histone deacetylase (HDAC) inhibitor, have been demonstrated in a pivotal phase II clinical trial, and chidamide has been approved by the China Food and Drug Administration (CFDA) as a treatment for relapsed or refractory peripheral T cell lymphoma (PTCL). This study sought to further evaluate the real-world utilization of chidamide in 383 relapsed or refractory PTCL patients from April 2015 to February 2016 in mainland China. For patients receiving chidamide monotherapy (n = 256), the overall response rate (ORR) and disease control rate (DCR) were 39.06 and 64.45%, respectively. The ORR and DCR were 51.18 and 74.02%, respectively, for patients receiving chidamide combined with chemotherapy (n = 127). For patients receiving chidamide monotherapy and chidamide combined with chemotherapy, the median progression-free survival (PFS) was 129 (95% CI 82 to 194) days for the monotherapy group and 152 (95% CI 93 to 201) days for the combined therapy group (P = 0.3266). Most adverse events (AEs) were of grade 1 to 2. AEs of grade 3 or higher that occurred in ≥5% of patients receiving chidamide monotherapy included thrombocytopenia (10.2%) and neutropenia (6.2%). For patients receiving chidamide combined with chemotherapy, grade 3 to 4 AEs that occurred in ≥5% of patients included thrombocytopenia (18.1%), neutropenia (12.6%), anemia (7.1%), and fatigue (5.5%). This large real-world study demonstrates that chidamide has a favorable efficacy and an acceptable safety profile for refractory and relapsed PTCL patients. Chidamide combined with chemotherapy may be a new treatment choice for refractory and relapsed PTCL patients but requires further investigation. Electronic supplementary material The online version of this article (doi:10.1186/s13045-017-0439-6) contains supplementary material, which is available to authorized users. more...

Methods (DOCX 16Â kb)

Drug-related adverse events in â Ľ5% of patients (DOCX 21Â kb)

Patientsâ baseline characteristics (DOCX 16Â kb)

Mutations in Janus kinase 2 (JAK2), myeloproliferative leukemia (MPL), and CALR are highly relevant to Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms.Assessing the prevalence of molecular mutations in Chinese Han patients with essential thrombocythemia (ET), and correlating their mutational profile with disease characteristics/phenotype.Of the 110 subjects studied, 62 carried the JAK2 V617F mutation, 21 had CALR mutations, one carried an MPL (W515) mutation, and 28 had non-mutated JAK2, CALR, and MPL (so-called triple-negative ET). Mutations in JAK2 exon 12 were not detected in any patient. Two ET patients had both CALR and JAK2 V617F mutations. Comparing the hematological parameters of the patients with JAK2 mutations with those of the patients with CALR mutations showed that the ET patients with CALR mutations were younger (p = 0.045) and had higher platelet counts (p = 0.043).Genotyping for CALR could be a useful diagnostic tool for JAK2/MPL-negative ET, since the data suggest that CALR is much more prevalent than MPL, therefore testing for CALR should be considered in patients who are JAK2 negative as its frequency is almost 20 times that of MPL mutation. more...

The goal is to develop and evaluate a new constrained feature-based cardiac motion estimation (ME) method for cardiac gated (CG) myocardial perfusion (MP) PET images to improve the accuracy of the estimated cardiac motion vector field (MVF). CG-MP PET projection data were generated from the 4D XCAT phantom with realistic anatomical structures and cardiac MVF models, and reconstructed using the STIR simulation and reconstruction software. The interventricular sulcus (IS) was extracted from each CG-MP PET image by applying B-spline extrapolation and interpolation methods to the extracted edges of the left (LV) and right ventricular (RV) walls. The estimated MVFs of the extracted ISs were calculated between adjacent CG frames. In the previously feature-based cardiac ME algorithm, the estimated IS MVF was used as an initial estimate in the conventional optical-flow ME algorithm. The information was found to reduce the aperture problem effect and provide more accurate cardiac MVF estimate as compared to without the information, using the cardiac MVF of the XCAT as the truth. In the new algorithm, it was used as an additional constraint to restrict the range of the search for the cardiac MVF estimate. The new approach was evaluated in terms of accuracy of the estimated cardiac MVF and compared with those using the previous methods. The evaluation results showed the estimated cardiac MVF obtained from using the IS as an initial estimate (S-initial) was more accurate than that using no initial estimate (0-initial) and was comparable to that using the truth MVF as the initial estimate (T-initial). The estimation accuracy was further improved with the S-initial and the IS motion as an additional constraint. In conclusion, we developed and evaluated a new constrained feature-based cardiac ME method for cardiac PET. We demonstrated the new method provided more accurate estimation of the cardiac MVF as compared to the conventional and a previously developed feature-based cardiac ME method for CG-MP PET. more...

This study aims to investigate whether neutrophil to lymphocyte ratio (NLR) is an independent predictor in newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients in the rituximab era. Data from newly diagnosed DLBCL patients at Nanjing Drum Tower Hospital from 2006 to 2015 were retrospectively reviewed. We used the receiver operating characteristic (ROC) curve analysis to generate the optimal cutoff value for NLR. Among those 156 patients enrolled, the NLR was < 3.0 in 46.8% (73/156) of the patients, and the remaining 53.2% (83/156) had an NLR ≥ 3.0. Patients with higher pretreatment NLR were found to correlate with poorer OS and PFS than these with lower NLR (hazard ratio [HR] = 2.66, 95% confidence interval [CI] = 1.43–4.97, P = 0.002 and HR = 1.79, 95% CI = 1.05–3.07, P = 0.034, respectively). The multivariate Cox proportional hazard model analysis further showed that high NLR was found independently predictive of poor OS (HR = 0.40; CI = 0.19–0.84, P = 0.015) and PFS (HR = 0.57; CI = 0.33–0.98, P = 0.042). Consequently, pretreatment NLR was an independent prognostic predictor in patients with DLBCL in the rituximab era. more...

We propose a new interior region-of-interest (ROI) image reconstruction method for emission tomography. The additional information to make the interior problem uniquely solvable is that a specific region inside the interior ROI is known to have uniform intensity level, but the constant level is unknown. The uniqueness of solution in this situation is analyzed by combining two existing approaches, namely (1) when the full knowledge of a small region inside the interior ROI is known, and (2) when the complete interior ROI is piecewise constant. The image reconstruction is provided by a mixed region and voxel based Poisson likelihood ML-EM algorithm that takes care of the photon statistics and the uniform attenuation effect in emission tomography. This algorithm reconstructs the unknown constant (region-model) and the rest of the interior ROI (voxel-model) simultaneously. The uniqueness result assumes that all line integrals through the interior ROI are acquired. When only a finite number of projection views are available, the mixed region and voxel based ML-EM algorithm can also reduce image artifacts from sparse-view and interior data acquisition in stationary multipinhole SPECT. more...

We describe an MR-compatible SPECT camera for small animals. The SPECT camera system can be inserted into the bore of a state-of-the-art MRI system and allows researchers to acquire tomographic images from a mouse in-vivo with the MRI and the SPECT acquiring simultaneously. The SPECT system provides functional information, while MRI provides anatomical information. Until today it was impossible to operate conventional SPECT inside the MRI because of mutual interference. The new SPECT technology is based on semiconductor radiation sensors (CZT, ASICs), and it fits into conventional high field MRI systems with a minimum 12-cm bore size. The SPECT camera has an MR-compatible multi-pinhole collimator for mice with a O25-mm field-of-view. For the work reported here we assembled a prototype SPECT camera system and acquired SPECT and MRI data from radioactive sources and resolution phantoms using the camera outside and inside the MRI. more...

Purpose: To develop a method to reconstruct an interior region-of-interest (ROI) image with sufficient accuracy that uses differentiated backprojection (DBP) projection onto convex sets (POCS) [H. Kudo et al., ''Tiny a priori knowledge solves the interior problem in computed tomography'', Phys. Med. Biol. 53, 2207-2231 (2008)] and a tiny knowledge that there exists a nearly piecewise constant subregion. Methods: The proposed method first employs filtered backprojection to reconstruct an image on which a tiny region P with a small variation in the pixel values is identified inside the ROI. Total variation minimization [H. Yu and G. Wang, ''Compressed sensing based interior tomography'', Phys. Med. Biol. 54, 2791-2805 (2009); W. Han et al., ''A general total variation minimization theorem for compressed sensing based interior tomography'', Int. J. Biomed. Imaging 2009, Article 125871 (2009)] is then employed to obtain pixel values in the subregion P, which serve as a priori knowledge in the next step. Finally, DBP-POCS is performed to reconstruct f(x,y) inside the ROI. Clinical data and the reconstructed image obtained by an x-ray computed tomography system (SOMATOM Definition; Siemens Healthcare) were used to validate the proposed method. The detector covers an object with a diameter of {approx}500 mm. The projectionmore » data were truncated either moderately to limit the detector coverage to diameter 350 mm of the object or severely to cover diameter 199 mm. Images were reconstructed using the proposed method. Results: The proposed method provided ROI images with correct pixel values in all areas except near the edge of the ROI. The coefficient of variation, i.e., the root mean square error divided by the mean pixel values, was less than 2.0% or 4.5% with the moderate or severe truncation cases, respectively, except near the boundary of the ROI. Conclusions: The proposed method allows for reconstructing interior ROI images with sufficient accuracy with a tiny knowledge that there exists a nearly piecewise constant subregion.« less more...

Purpose: A rotating multi-segment slant-hole (RMSSH) collimator is able to provide much higher ( ∼ 3 times for four-segment collimator with 30° slant angle) sensitivity than a parallel-hole (PH) collimator with the similar spatial resolution for imaging small organs such as the heart and the breast. In this article, the authors evaluated the performance of myocardial perfusion SPECT (MPS) using a RMSSH collimator compared to MPS using the low-energy high-resolution parallel-hole collimators. Methods: The authors conducted computer simulation studies using the NURBS-based cardiac-torso phantom, receiver operative characteristic (ROC) analysis using the channelized Hotelling observer, physical phantom experiments, and pilot patient studies to evaluate the performance of MPS using a rotating four-segment slant-hole (R4SSH) collimator with respect to MPS using a PH collimator. Results: In the simulation study, the R4SSH MPS provides images with superior contrast-noise trade-off than those of PH MPS with the same acquisition time. The defect detectability in terms of the largest area under the ROC curve for R4SSH MPS is significantly higher than those of PH MPS with p -values 0.01 . In the phantom experiments, the R4SSH MPS images with 7.5 min acquisition had similar noise level and overall image quality as those of PH MPS with 21 min acquisition. Pilot patient studies showed that with the same acquisition time, the R4SSH SPECT using a single-head camera gave images with similar quality as those of PH SPECT using a dual-head camera. Conclusions: The RMSSH SPECT has a potential to improve the coronary artery disease detection and workflow of SPECTimaging acquisition due to the high sensitivity property of the RMSSH collimator. more...

Antifungal prophylaxis using fluconazole or itraconazole has been studied for many years but still no consensus has been reached regarding their safety and effectiveness. We performed a systematic meta-analysis to assess the efficacy of fluconazole compared to itraconazole in neutropenic patients with hematological malignancies. We gathered the data for our analysis from MEDLINE, EMBASE, Cochrane-controlled trials register, Cochrane Library, and Science Citation Index (1/1990 to 1/2009) searches. Risk ratio (RR) and 95% confidence intervals (CIs) were calculated using the random effect model. Nine RCTs were identified that were published in full text. Significantly, fewer patients were withdrawn from the studies due to the development of adverse effects with fluconazole prophylaxis when compared with itraconazole (RR 0.45, 95% CI 0.27–0.75, P = 0.002). There were statistically significant differences regarding fungal infections (RR 1.34, 95% CI 1.08–1.67, P = 0.009) and invasive fungal infections (RR 1.33, 95% CI 1.02–1.73, P = 0.03) between the two educations. There were no statistically significant differences regarding overall mortality (RR 0.95, 95% CI 0.77–1.17, P = 0.64), fungal-related mortality (RR 1.28, 95% CI 0.80–2.07, P = 0.31), and proven fungal infections (RR 1.38, 95% CI 0.75–2.53, P = 0.30). The analysis of published evidence reveals that itraconazole administration resulted in significantly fewer episodes of fungal infections and invasive fungal infections compared with fluconazole. more...

T-cell acute lymphoblastic leukemia (T-ALL) results from the collaboration of multiple genetic abnormalities in the transformation of T-cell progenitors. Plant homeodomain finger protein 6 (PHF6) has recently been established as a key tumor suppressor, which is mutated in T-ALL; however, the clinical significance of PHF6 mutations has not been fully determined in adult T-ALL. In the present study, amplification of the PHF6 exons was performed, followed by DNA sequencing to identify the genomic mutations and examine the expression of PHF6 in adult patients with T-ALL. The correlation between PHF6 mutations and clinical features was also analyzed using a χ2 test, and between PHF6 mutations and survival curve using the Kaplan-Meier methods. PHF6 mutations were detected in 27.1% of the Chinese adults with T-ALL (16/59), 10 of which were found to be novel mutations. A significantly lower expression level of PHF6 was observed in T-ALL patients with PHF6 mutations compared with those without mutations. Of the observed mutations in PHF6, 6/16 were frame-shift mutations, indicating a PHF6 dysfunction in those patients. Of note, PHF6 mutations were found to be significantly associated with older age, lower hemoglobin levels, higher frequency of CD13 positivity and higher incidence of splenomegaly or lymphadenopathy. Furthermore, PHF6 mutations were found to be significantly correlated with Notch homolog 1, translocation-associated (Drosophila) (NOTCH1) mutations. The patients with T-ALL with co-existence of the two mutations had a significantly shorter event-free survival and a poor prognosis. The present results indicated that PHF6 is inactivated in adult T-ALL, due to its low expression and mutations. The present data indicated the synergistic effect of PHF6 and NOTCH1 mutations, as well as their co-existence, on the oncogenesis of adult T-ALL, and their potential as a prognostic marker for the disease. more...

Quantitative four-dimensional (4D) image reconstruction methods with respiratory and cardiac motion compensation are an active area of research in ECT imaging, including SPECT and PET. They are the extensions of three-dimensional (3D) statistical image reconstruction methods with iterative algorithms that incorporate accurate models of the imaging process and provide significant improvement in the quality and quantitative accuracy of the reconstructed images as compared to that obtained from conventional analytical image reconstruction methods. The new 4D image reconstruction methods incorporate additional models of the respiratory and cardiac motion of the patient to reduce image blurring due to respiratory motion and image noise of the cardiac-gated frames of the 4D cardiac-gated images. We describe respiratory motion estimation and gating method based on patient PET list-mode data. The estimated respiratory motion is applied to the respiratory gated data to reduce respiratory motion blur. The gated cardiac images derived from the list-model data are used to estimate cardiac motion. They are then used in the cardiac-gated images summing the motion-transformed cardiac-gated images for significant reduction in the gated images noise. Dual respiratory and cardiac motion compensation is achieved by combining the respiratory and cardiac motion compensation steps. The results are further significant improvements of the 4D gated cardiac PET images. The much improved gated cardiac PET image quality increases the visibility of anatomical details of the heart, which can be explored to provide more accurate estimation of the cardiac motion vector field and cardiac contractility. more...

OBJECTIVE The study aimed to evaluate the influence of repeated recruitment manoeuvres (RRMs) on lung injury in patients with acute respiratory distress syndrome (ARDS). METHODS Forty-one ventilated patients with severe ARDS were selected for this study. Recruitment manoeuvres (RMs) were conducted with continuous positive airway pressure (CPAP; 30 cm H2O for 40 seconds). Recruitment manoeuvres were repeated every two hours for all three groups. Changes in haemodynamics, pulmonary compliance, gas exchange and extravascular lung water index (EVLWI) were monitored before RM (pre-RM), 10 minutes after each RM, and four hours after RM3 (4 hours post-RRM). Pulmonary inflammatory factors (tumour necrosis factor-alpha [TNF-α] and interleukin [IL]-6 and -10) were also analysed. RESULTS Compared with those in pre-RM, pulmonary compliance, oxygenation index (ratio of partial pressure of arterial oxygen to fraction of inspired oxygen [PaO2/FiO2]) and EVLWI remarkably improved in RM1, RM2, RM3 and 4 hours post-RRM (p < 0.05). The PaO2/FiO2 ratio increased significantly in RM1 and RM3 (p < 0.05). Extravascular lung water index decreased significantly in RM1 compared with that in RM3 and 4 hours post-RRM (p < 0.05). There was no significant difference in cytokines. CONCLUSION Repeated recruitment manoeuvres during lung-protected ventilation can improve pulmonary compliance and oxygenation and significantly decrease extravascular lung water in ARDS patients. Lung injury was not worsened by RRMs in patients with severe ARDS. more...

Rotating multi-segment slant-hole (RMSSH) SPECT is suitable for detecting small and low-contrast breast lesions since it has much higher detection efficiency compared with parallel-hole SPECT for the same resolution and can image the breast at a closer distance. Our RMSSH SPECT image reconstruction extends a previous rotation-shear transformation based 3D iterative reconstruction method to include non-uniform attenuation compensation. Reconstructed RMSSH SPECT images with attenuation compensation show much improved quantitative accuracy and less image artifacts than without. We conclude that attenuation compensation provides RMSSH SPECT images with improved quality and quantitative accuracy. more...