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The objective of this study was to investigate the clinical significance of minimal residual disease (MRD) monitoring through Wilms tumor 1 (WT1) gene expression and multicolor flow cytometry (FCM) in patients with chronic myelomonocytic leukemia (CMML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).For this purpose, WT1 gene expression and the CMML-related abnormal immunophenotype were examined using real-time quantitative polymerase chain reaction and FCM, respectively.In total, 59 patients with CMML who underwent allo-HSCT were enrolled in this study. Thirteen cases (22.0%) developed hematological relapse, and 15 patients (25.4%) expired during the follow-up period. Thirty-four patients (37.6%) were positive for WT1 (WT1+), and 44 patients (74.6%) were positive for FCM prior to allo-HSCT. After allo-HSCT, there were 21 WT1+ patients (35.6%) and 10 patients (16.9%) who were positive in FCM (FCM+). Post-transplant WT1+ (post-WT1 0.6+; 50.7% vs. 7.6%, p .001) and post-transplant FCM+ (post-FCM+; 90.0% vs. 8.8%, p .001) indicated a higher 3-year cumulative incidence of relapse (CIR) compared with the WT1- or FCM-patients. Multivariate analysis of event-free survival (EFS), overall survival (OS), and CIR showed that the FCM status after transplantation was an independent prognostic factor for relapse (p .05).Both FCM and WT1 after HSCT were identified as important predictors of recurrence of CMML following transplantation and may be useful in guiding interventions against disease relapse.

Acute myeloid leukaemia (AML) patients with tumour protein p53 (TP53) mutations are often resistant to chemotherapy and have worse clinical outcomes than patients without TP53 mutations. In this study, we compared clinical outcomes of patients with AML with and without TP53 mutations who underwent haploidentical haematopoietic stem cell transplantation (haplo-HSCT). For the TP53-mutation group and TP53 wild-type group, the 2-year cumulative incidence of relapse (CIR) was (39.0% vs. 21.2% respectively, p = 0.088), the 2-year non-relapse mortality (NRM) rate was (3.2% vs. 8.4% respectively, p = 0.370), the 2-year leukaemia-free survival (LFS) was (57.7% vs. 71.3% respectively, p = 0.205), the 2-year overall survival (OS) rate was (69.9% vs. 81.3% respectively, p = 0.317), the 100-day cumulative incidence of Grade II-IV acute graft-versus-host disease (GvHD) was (6.5% vs. 20.7% respectively, p = 0.074), the 2-year cumulative incidence of chronic GvHD was (52.3% vs. 53.1% respectively, p = 0.493) and the 2-year GvHD-free/relapse-free survival (GRFS) was (57.7% vs. 69.6% respectively, p = 0.347). Our data showed that there were no significant differences in 2-year clinical outcomes between the two groups. Multivariable analysis showed TP53 mutations had no significant impact on CIR, NRM, OS, GvHD, LFS or GRFS. Our findings suggest that patients with AML with TP53 mutations may at least partially benefit from haplo-HSCT. Haplo-HSCT might be the recommended treatment for such patients.

Multiple myeloma (MM) is a cancer of malignant plasma cells in the bone marrow and extramedullary sites. We previously characterized a VQ model for human high-risk MM. Different VQ lines display distinct disease phenotypes and survivals, suggesting significant intra-model variation. Here, we use whole exome sequencing and copy number variation (CNV) analysis coupled with RNA-Seq to stratify VQ lines into corresponding clusters: Cluster I VQ cells carried recurrent amplification of chromosome (chr) 3 and displayed upregulation of growth pathways and high-risk myeloma gene signatures, whereas Cluster II cells had monosomy chr5 and overexpressed genes and pathways associated with positive response to bortezomib (Btz) treatment in human MM patients. Consistently, in sharp contrast to Cluster II VQ cells that showed short-term response to Btz, Cluster I VQ cells were de novo resistant to Btzin vivo. Our study highlights Cluster I VQ lines as highly representative of human high-risk MM subset.

Haploidentical hematopoietic stem cell transplant (haplo-HSCT) provides an important alternative for children and adolescents with acquired severe aplastic anemia (SAA) lacking matched donors. To test whether pretransplant serum ferritin (SF) represents a candidate predictor for survival and a potential biomarker for graft-versus-host disease (GvHD) in pediatric haplo-HSCT, we retrospectively evaluated 147 eligible patients with SAA who underwent haplo-HSCT. The patients were divided into the low-SF group ( 1000 ng/mL) and the high-SF group (≥ 1000 ng/mL). We found that SF ≥1000 ng/mL independently increased the risk of grade II-IV aGvHD (HR = 2.596; 95% CI, 1.304-5.167, P = 0.007) and grade III-IV aGvHD (HR = 3.350; 95% CI, 1.162-9.658, P = 0.025). Similar probabilities of transplant-related mortality at 100 days were observed in the two groups (6.19 ± 2.45% vs 8.00 ± 3.84%, P = 0.168). The two-year overall survival (85.29 ± 3.89% vs 92.00% ± 3.84%, P = 0.746) and failure-free survival (83.23% ± 4.08% vs 83.37% ± 6.27%, P = 0.915) were comparable. GvHD-/failure-free survival were 60.06 ± 5.10% and 75.56 ± 6.87%, respectively (P = 0.056). In conclusion, elevated pretransplant SF level is associated with higher incidences of grade II-IV aGvHD and grade III-IV aGvHD. However, it is not associated with worse survival after haplo-HSCT for children and adolescent patients with SAA.

Background The introduction of mold-active antifungal drugs has led clinicians to reconsider the use of fluconazole for preventing invasive fungal disease (IFD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study of recipients of allo-HSCT, we evaluated the effects of different antifungal prophylaxes on the incidence of IFD at different times after transplantation. Methods Among the 1,401 patients registered in the prospective China Assessment of Antifungal Therapy in Haematological Disease (CAESAR) study database, there were 661 eligible patients who received primary antifungal prophylaxis. The incidence of IFD at different times after transplantation (early, late, and very late) and overall survival were compared for patients who received different drugs. Results The overall incidence of probable IFD was 7.0% in the fluconazole group, 12.6% in the itraconazole group, 1.4% in the voriconazole group, and 5.2% in the micafungin group (P=0.0379). However, the four groups had no significant differences in early, late, or very late IFD. The risk factors associated with IFD were neutropenia for more than 14 days, age greater than 18 years, and receipt of transplantation from an alternative (unrelated and haploidentical) donor (P

Low production cost and ever-increasing efficiencies make perovskite solar cells a flourishing area of research. The high efficiency originates from not only the unique optoelectronic properties of perovskites, but also various device optimization strategies, such as interfacial engineering, defect engineering, and componential engineering. Behind these strategies stand the fundamental intermolecular interactions and bondings, such as hydrogen bonding, halide bonding, ionic bonding, Lewis acid–base interactions, and van der Waals interactions. In this review, we focus on different types of interactions and summarize the progresses made in perovskite solar cells. Additionally, perspectives on further efforts in improving device performance and stability are presented.

Revascularization is an effective therapy for rescuing myocardial tissue after ischemic events. However, the process of reperfusion can lead to more severe cardiomyocyte damage, called myocardial ischemia-reperfusion (I/R) injury (MIRI). We have previously shown that vitexin (VT) (a flavonoid compound derived from natural products) protects against MIRI; however, the exact mechanisms underpinning this effect require further elucidation. This study is aimed at elucidating the protective mechanism of VT in inhibiting ischemic myocardial mitochondrial dysfunction and reducing cardiomyocyte apoptosis by regulating Epac1-Rap1 signaling. Isolated rat hearts were subjected to MIRI in a Langendorff perfusion system, and H9c2 cells were subjected to hypoxia/reoxygenation (H/R) in vitro. Our analyses show that during I/R, Epac1 expression was upregulated, left ventricular dysfunction deteriorated, mitochondrial dynamics were disrupted, and both myocardial cells and tissues exhibited apoptosis. Furthermore, administration of 8-CPT (an Epac agonist) exacerbated cardiomyocyte injury and mitochondrial dysfunction. Interestingly, suppressing the function of Epac1 through VT or ESI-09 (an Epac inhibitor) treatment during I/R reduced the myocardial infarct size, cardiomyocyte apoptosis, and reactive oxygen species production; alleviated mitochondrial dysfunction by increasing mitochondrial membrane potential; elevated MFN2 expression; and inhibited Drp1 expression. To our knowledge, our results reveal, for the first time, the mechanisms underlying the protective effect of VT in the myocardium of rats with MIRI. Moreover, we provide a new target and theoretical basis for VT in the treatment of ischemic heart disease.

We report a case of coronavirus disease 2019 (COVID-19) after haploidentical transplantation with acute graft-versus-host disease (aGVHD). COVID-19 and aGVHD were improved under treatment with arbidol, remdesivir, methylprednisolone, and ruxolitinib. However, eventually, the patient died of septic shock and multiple organ failure. It was concluded that the disease condition of this COVID-19 patient after transplantation was serious, complex, and variable, with poor prognosis.

Relapse is the main problem after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The outcome of a second allo-HSCT (HSCT2) for relapse post-HSCT has shown promising results in some previous studies. However, little is known about the efficacy of HSCT2 in patients with relapsed/refractory acute leukemia (AL) post-chemotherapy plus modified donor lymphocyte infusion (post-Chemo + m-DLI) after the first allo-HSCT (HSCT1). Therefore, we retrospectively analyzed the efficacy of HSCT2 in 28 patients with relapsed/refractory AL post-Chemo + m-DLI in our center. With a median follow-up of 918 (457-1732) days, 26 patients (92.9%) achieved complete remission, and 2 patients exhibited persistent disease. The probabilities of overall survival (OS) and disease-free survival (DFS) 1 year after HSCT2 were 25.0% and 21.4%, respectively. The cumulative incidences of nonrelapse mortality on day 100 and at 1 year post-HSCT2 were 7.1% ± 4.9% and 25.0% ± 8.4%. The cumulative incidences of relapse were 50.0% ± 9.8% and 53.5% ± 9.9% at 1 and 2 years post-HSCT2, respectively. Risk stratification prior to HSCT1 and percentage of blasts before HSCT2 were independent risk factors for OS post-HSCT2, and relapse within 6 months post-HSCT1 was an independent risk factor for DFS and relapse post-HSCT2. Our findings suggest that HSCT2 could be a salvage option for patients with relapsed AL post-Chemo + m-DLI.

A dialkoxyl-substituted naphthodithieno[3,2-b]thiophene-based copolymer (PV12) was applied as a third component for ternary polymer solar cells (PSCs) based on PCDTBT1−x:PV12x:PC71BM. In Al-only ternary PSCs with x = 0.15, a power conversion efficiency (PCE) of 6.73% was achieved due to simultaneous enhancement in the open circuit voltage, short circuit current and fill factor, which is much higher than the PCE of 5.28% for Al-only binary PSCs based on PCDTBT:PC71BM and 2.93% for Al-only binary PSCs based on PV12:PC71BM. The PCE reached 7.69% when IIDTh-NSB as a cathode interlayer was introduced between the ternary active layer and Al. Ultraviolet photoemission spectroscopy measurements demonstrated a cascade-type energy level alignment at the ternary PCDTBT(D1)/PV12(D2)/PC71BM(A) junction. As a result, the voltage limitation was overcome at the D1/D2/A junction. Ultraviolet-visible absorption and external quantum efficiency spectra showed that PV12 had complementary absorption to PCDTBT in the solar spectrum. Atomic force microscopy and transmission electron microscopy images showed that the morphology and phase separation of the active layer were optimized by adding PV12. Photoluminescence spectral investigations suggested that the Forster resonance energy transfer from PCDTBT to PV12 occurred in the ternary PSCs under illumination. Finally, the PCEs of the ternary PSCs are not as sensitive to the thickness of the active layer as those of the binary PSCs, which is important for the roll-to-roll coating processing of organic photovoltaic modules.

This study with subjects of 345 sales service personnel, examines the organization atmosphere and psychological capital in the customer’s verbal abuse and sales staff turnover intention and job burnout of the influence of the adjustment. It was found that: 1) verbal violation of the customer had a significant positive correlation with the tendency to resign and job burnout; 2) psychological capital has a negative moderating effect on the relationship between verbal abuse and turnover intention of sales staff; 3) organization atmosphere has negative moderating effect on the relationship between customer’s verbal violation and sales staff’s turnover intention and job burnout.

T cell hyporesponsiveness is crucial for functional immune system and prevent the damage induced by alloreactive T cells in autoimmune pathology and transplantation. As one of the most important regulators during B cell development, PRDM1 (also known as BLIMP-1) has been demonstrated its essential role for maintaining T cell hyporesponsiveness and homeostasis, evidenced by Prdm1 deficient mice accumulating activated T cells and developing multiorgan inflammatory disease. However, the mechanism of PRDM1 regulating T cell hyporesponsiveness is still ambiguous. In this study, we took advantage of multiomics technologies and systemic report the central role of PRDM1 in inducing human primary T cell hyporesponsiveness. Firstly, we overexpressed PRDM1 in human primary T cells and found increased ratio of CD4 +CD25 +FOXP3 + Treg cell subsets and increased IL-4 secretion. In parallel, inhibited PRDM1 expression level in human T cells decreased ratio of Treg cells and secretion of IL-4. Meanwhile, transcriptome analyses revealed that overexpressed PRDM1 enriched negative regulation of cell proliferation signaling pathway and resulted in a global reduction in IL-2 and inflammatory response signaling pathways. Furthermore, overexpressed PRDM1 in primary T cells upregulated several negative regulators of T cell function like EOMES, KLF2, LILRB1, KLRB1 and CD244, indicating a pioneer role of PRDM1 in inducing T cell hyporesponsive. To further investigate the regulation role of T cell hyporesponsiveness of PRDM1, we performed CUT&Tag and ATAC-seq in PRDM1 overexpressed primary T cells. CUT&Tag analysis showed PRDM1 could directly upregulated T cell hyporesponsiveness related gene such as KLF2, CD244 and KLRD1. Importantly, we observed consistent changes of IL-2, central regulator of T cell activation, in PRDM1 overexpressed T cell from ATAC-seq, CUT&Tag and RNA-seq data. We found PRDM1 could binding to IL-2 locus and decreased the chromatin accessibility of IL-2, consequently downregulated the expression level of IL-2 in human primary T cells. Moreover, altered open chromatin regions (OCRs) in PRDM1 overexpressed T cells enriched the similar transcription factors (TFs) with PRDM1 binding sites, indicating PRDM1 might be a pioneer TF in T cell hyporesponsiveness. These results demonstrated PRDM1 is sufficient for inducing T cell hyporesponsiveness in human primary T cells. To further validate the coexpression relationship between PRDM1 and Treg cell central TF FOXP3, we upregulated PRDM1 expression level on Jurkat T cells lines. The results also showed that elevated FOXP3 both in mRNA and protein level accompanied with upregulated PRDM1 expression level. To analyze the mechanism of PRDM1 regulating FOXP3 expression level, CUT&Tag data analyses showed that PRDM1 might upregulated FOXP3 by directly binding to the enhancer region of upstream of FOXP3 locus. Meanwhile, PRDM1 indirectly upregulated FOXP3 by upregulated KLF2, evidenced by inhibiting KLF2 in PRDM1 overexpressed primary T cells downregulated FOXP3 expression level. To further investigate the clinical implication of PRDM1 inducing T cell hyporesponsiveness, we detected the relationship of PRDM1 expression level and acute graft-versus-host disease(aGVHD) occurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our results showed that patients with aGVHD (n=7) exhibited lower PRDM1 expression level than those without aGVHD in the same period after HSCT (n=7). Furthermore, we detected the expression level of PRDM1 in CD4 + T cell and CD8 + T cells from bone marrow allografts (BM) or peripheral blood allografts (PB) and followed up the occurrence of GVHD after HSCT for 2 years (n=18). There are low expression levels of PRDM1 in CD4 + T cells both from BM or PB grafts corelated with aGVHD occurrence in patients after allo-HSCT compared with those without aGVHD occurrence. In conclusion, our study provides the global regulatory model of PRDM1 in human primary T cell. We introduced PRDM1 as a sufficient regulator in T cell hyporesponsiveness induction, which is altering the chromatin accessibility and directly upregulated T cell inhibitory signals and downregulated T cell activated signals. The negative relationship between PRDM1 expression level with GVHD occurrence indicated it might be a potential biomarker for indicating HSCT prognosis. Disclosures No relevant conflicts of interest to declare.

We present PaCaPa, a handheld device that renders haptics on a user's palm when the user interacts with virtual objects using virtual tools such as a stick. PaCaPa is a cuboid device with two wings that open and close. As the user's stick makes contact with a virtual object, the wings open by a specific degree to dynamically change the pressure on the palm and fingers. The open angle of the wings is calculated from the angle between the virtual stick and hand direction. As the stick bites into the target object, a large force is generated. Our device enables three kinds of renderings: size, shape, and stiffness. We conducted user studies to evaluate the performance of our device. We also evaluated our device in two application scenarios. User feedback and qualitative ratings indicated that our device can make indirect interaction with handheld tools more realistic.

A ligand-free copper(I)-catalyzed benzylic acyloxylation of 2-alkylpyridines with carboxylic acids was realized by using 1.0 atm of O2 as a green oxidant. The transformation provided a facile access to a wide range of N-heterocyclic esters through C–O bond formation, with broad substrate scope and good functional group tolerance. Preliminary mechanistic investigations showed that this protocol included a radical process.

In this investigation, a novel anionic- halogen-free ionic liquid (IL), 1-butyl-3-methylimidazolium dodecyl sulfate ([C4mim][C12SO4]), was synthesized and examined for possible application in the chemical enhanced oil recovery (EOR) processes. In this way, the effects of [C4mim][C12SO4] and NaCl concentrations, temperature and model oil type (aliphatic and aromatic hydrocarbons) on interfacial tensions (IFTs) between [C4mim][C12SO4] solutions and model oils were systematically investigated. It is surprisingly revealed that the novel SAIL [C4mim][C12SO4] is highly effective in reducing the IFT of aromatic hydrocarbon/water system, and ultra-low IFT can be achieved in the presence of salinity at higher temperature. Moreover, the interaction energies between [C4mim][C12SO4] and different model oil molecules were calculated using molecular mechanics, which could further interpret the reasons of ultra-low IFT.

PaCaPa is a handheld device that presents haptic stimuli on a user's palm when the user interacts with virtual objects using virtual tools. It is a box-shaped device and has two wings. This device can present the contact force and contact angle by opening and closing the wings based on the angle between the direction of the virtual tool and hand. By changing these haptic sensations on the palm and fingers, it enables the users to perceive different size, shape, and stiffness of virtual objects.

The absence of tactile cues such as keys and buttons makes touchscreens difficult to navigate for people with visual impairments. Increasing tactile feedback and tangible interaction on touchscreens can improve their accessibility. However, prior solutions have either required hardware customization or provided limited functionality with static overlays. Prior investigation of tactile solutions for large touchscreens also may not address the challenges on mobile devices. We therefore present Interactiles, a low cost, portable, and unpowered system that enhances tactile interaction on Android touchscreen phones. Interactiles consists of 3D-printed hardware interfaces and software that maps interaction with that hardware to manipulation of a mobile app. The system is compatible with the built-in screen reader without requiring modification of existing mobile apps. We describe the design and implementation of Interactiles, and we evaluate its improvement in task performance and the user experience it enables with people who are blind or have low vision.

Recommendation system, as one of cost effective solutions dealing with the information-overwhelming problem, has been adopted by many internet e-commerce platforms, such as Amazon, eBay, Asos, etc. User-based or item-based collaborative filtering, as one of the classic recommendation algorithms, suffers greatly from high computational consumption and matrix complexity when big data is involved. While neural network architecture based deep learning technique, on the other hand, performs outstandingly as an alternative solution solving regression and classification problems, especially with sparse inputs. Furthermore, deep learning alleviates the cold start problem to a certain extent which is an unavoidable flaw in collaborative filtering (CF) approach based recommendation algorithms. This paper proposes a deep learning network structure which utilizes the Restricted Boltzmann Machine and the artificial neural network for Weibo Users. The proposed structure is trained and tested through the actual dataset provided by VComic, who is an online comic book provider and shares the information with China's biggest social network — Weibo.com. The offline experiment shows that the proposed system outperforms the user-based collaborative filtering algorithm in the metrics of precision and coverage. Specifically, the proposed mechanism demonstrates the ability to mine the long tail under the premise of accuracy guarantee, as well as to reduce the system's complexity dramatically.

For adult patients with intermediate-risk acute myelogenous leukemia (AML) in first complete remission (CR1), allogeneic stem cell transplantation (allo-SCT) has been demonstrated to be the best therapeutic option. The ideal donor is a HLA-genoidentical sibling. In the absence of a genoidentical donor, a HLA 10/10 or 8/8 matched unrelated donor (URD) is presently considered to be the best choice, taking advantage of the 25 million volunteer donors registered worldwide.1 Although the probability of finding an unrelated donor has recently reached almost 80% for white Europeans, it still remains at around only 41% for Chinese patients.2 Furthermore, while waiting for a volunteer donor, the risk of early relapse remains, highlighting the need for alternative sources of donors.

Alcohol-soluble isoindigo derivative with thiophene groups and sulfobetaine zwitterions, IIDTh-NSB was applied as a novel modifier of ZnO in inverted polymer solar cells (i-PSCs). When IIDTh-NSB (0.2 mg/mL) was spin-coated on ZnO as an electron transport layer (ETL), power conversion efficiency (PCE) of the PTB7:PC71BM based i-PSCs reached 8.88%, which is a 20% improvement of that of 7.40% for the device with the ZnO-only ETL. If ZnO was doped by IIDTh-NSB of 1.0 wt %, the PCE of 8.50% could be achieved in the i-PSCs. Combined measurements of capacitance-voltage characteristics, carrier mobility, and photocurrent density-effective voltage characteristics revealed that incorporating IIDTh-NSB as the modifier of ZnO by coating or doping enhanced the built-in potential, charge carrier density and mobility, exciton dissociation, and charge carrier extraction in the i-PSCs because of the improved interfacial contact between the photoactive layer and ZnO as shown in water contact angle measurements and atomic force microscopy images. Finally, impedance spectroscopy investigation provided strong lines of evidence that incorporating IIDTh-NSB as the modifier of ZnO led to the great enhancement in short-circuit current density and fill factor. Furthermore, all the devices with IIDTh-NSB as a modifier of ZnO presented better stability than the device with ZnO-only. These findings suggest that IIDTh-NSB is an effective and competitive material for modification of ZnO in the i-PSCs.

The MicroComic Website underneath the Chinese biggest social network Sina.com (Comic.sina.com.cn) provides a broad range of comics for a huge set of users. The demand of a personalized recommendation system for comic readers has been put on the table recently to improve the users' experience. This paper first investigates the classic item-based collaborative filtering and latent factor model via utilizing the official data sets provided by the Sina.com Company. Then a hybrid recommendation approach is proposed to enhance the recommender performance. The recommendation system can estimate each individual user's preference of the unread comics and generate recommendation list of comics with relative high ratings. The proposed recommender achieves not only good prediction accuracy but outperforms the current recommendation system in respect of Coverage.

Hashimoto's encephalopathy (HE) is an acute encephalopathy associated with Hashimoto's thyroiditis. The majority of reported cases have been associated with hypothyroidism, while cases with hyperthyroidism are rare. The current study reported on a 56-year old female patient with HE, who was found to have progressively aggregated dysarthria, gait disturbance, somniloquy and delirium. Thyroid function tests revealed that the patient had hyperthyroidism, with high levels of anti-thyroid antibodies. Following treatment with corticosteroids, the neurological/psychiatric symptoms of the patient were relieved quickly. The one-year follow-up investigation indicated that there was no recurrence of the disease, demonstrating that the treatment administered for this rare case was effective.

Severe graft-versus-host disease is a major barrier for non-T-cell-depleted haploidentical stem cell transplantation. There is no consensus on the optimal graft-versus-host disease prophylaxis. This study compared the two most commonly used graft-versus-host disease prophylaxis regimens (post-transplant cyclophosphamide-based vs. the anti-thymocyte globulin-based) in adults with acute myeloid leukemia reported to the European Society for Blood and Bone Marrow Transplantation. A total of 308 patients were analyzed; 193 received post-transplant cyclophosphamide-based regimen and 115 anti-thymocyte globulin-based regimen as anti-graft-versus-host disease prophylaxis. The post-transplant cyclophosphamide-based regimen was more likely to be associated to bone marrow as graft source (60% vs. 40%; P=0.01). Patients in the post-transplant cyclophosphamide-based regimen group had significantly less grade 3-4 acute graft-versus-host disease than those in the anti-thymocyte globulin-based group (5% vs. 12%, respectively; P=0.01), comparable to chronic graft-versus-host disease. Multivariate analysis showed that non-relapse mortality was lower in the post-transplant cyclophosphamide-based regimen group [22% vs. 30%, Hazard ratio (HR) 1.77(95%CI: 1.09-2.86); P=0.02] with no difference in relapse incidence. Patients receiving post-transplant cyclophosphamide-based regimen had better graft-versus-host disease-free, relapse-free survival [HR 1.45 (95%CI: 1.04-2.02); P=0.03] and leukemia-free survival [HR 1.48 (95%CI: 1.03-2.12); P=0.03] than those in the anti-thymocyte globulin-based group. In the multivariate analysis, there was also a trend for a higher overall survival [HR 1.43 (95%CI: 0.98-2.09); P=0.06] for post-transplant cyclophosphamide-based regimen versus the anti-thymocyte globulin-based group. Notably, center experience was also associated with non-relapse mortality and graft-versus-host disease-free, relapse-free survival. Haplo-SCT using a post-transplant cyclophosphamide-based regimen can achieve better leukemia-free survival and graft-versus-host disease-free, relapse-free survival, lower incidence of graft-versus-host disease and non-relapse mortality as compared to anti-thymocyte globulin-based graft-versus-host disease prophylaxis in patients with acute myeloid leukemia.

To measure proinsulin concentrations in different states of glucose tolerance and examine the relationship between proinsulin and beta cell function. Serum true insulin (TI), proinsulin (PI), immunoreactive insulin (IRI), C peptide (CP) and blood glucose (BG) levels were measured in the fasting state and during an oral glucose tolerance test (OGTT) in 32 individuals with normal glucose tolerance (NGT), 42 individuals with impaired glucose tolerance (IGT), and 54 individuals with newly diagnosed type 2 diabetes mellitus. All participants were also subdivided into nonobese [body mass index (BMI)

In this study, the toxicity, behavioural and regeneration effects of dimethylformamide (DMF) on planarian Dugesia japonica were investigated. One control and six different concentrations of DMF (10 ppm, 100 ppm, 500 ppm, 1000 ppm, 5000 ppm and 10,000 ppm) were used in triplicate. The results showed that the mortality was directly proportional to the DMF concentration and planarian locomotor velocity (pLMV) was significantly reduced by increasing the exposure time and DMF concentration. pLMV of D. japonica was significantly reduced at a lower concentration of 10 ppm after 7 days of continuous exposure to DMF. The recovery of the motility of planarians pretreated with DMF was found to be time- and dose dependent, all planarians had complete recovery in their motility after 48 h. The appearance of auricles in regenerating animals was easily affected by DMF exposure in comparison with the appearance of eyespot. The present results suggest that the intact adult mobility in the aquatic planarian D. japonica is a more sensitive biomarker than mortality, and the appearance of auricles in regenerating animals is a more sensitive biomarker than eyespot.

By playing a direct proatherogenic role, C-reactive protein (CRP) is a potent independent predictor of future cardiovascular events. CRP is predominately synthesized by hepatocytes when stimulated by interleukin-6 (IL-6). In response to IL-6, the signal transducer and activator of transcription 3 (STAT3) becomes phosphorylated on tyrosine and serine residues. Phosphorylated STAT3 then activates CRP gene transcription. In obesity-related disorders such as diabetes, metabolic syndrome, and cardiovascular diseases, the circulating levels of CRP and adiponectin are inversely correlated, suggesting that these two factors might reciprocally regulate each other. We investigated the possibility that adiponectin inhibits CRP production in HepG(2) cells elicited by IL-6. CRP gene expression was determined using ELISA and semi-quantitative RT-PCR, and the phosphorylation of STAT3 was investigated with western blot. Adiponectin reduced IL-6-induced CRP mRNA levels in HepG(2) cells and CRP protein secretion. Preincubating HepG(2) cells with adiponectin led to a decline in STAT3 phosphorylation on both tyrosine and serine residues. Our results demonstrated that adiponectin suppresses CRP synthesis and secretion from HepG(2) cells and suggested that the suppression may be mediated through inhibition of the STAT3 pathway. The finding provides a novel insight into the molecular linkage between obesity and vascular diseases.

The aim of this study was to investigate the prevention of diet-induced obesity by a high safflower oil diet and adipocytic gene expression in mice. Forty 3-week-old C57BL/6 mice were randomly divided into three groups: control group (CON, 5% lard 1 5% safflower oil), high lard group (LAR, 45% lard 1 5% safflower oil), and high safflower oil group (SAF, 45% safflower oil 1 5% lard). After 10 weeks, 10 mice of the LAR group were switched to high safflower oil diet (LAR–SAF). Ten weeks later, glucose tolerance tests were performed by intraperitoneal injection of glucose. Circulating levels of lipid and insulin were measured and white adipose tissues were taken for gene chip and reverse transcriptase–polymerase chain reaction analysis. The LAR group showed higher body weight, adiposity index, insulin, and lipids than the CON group (P < 0.05). The body weight in the LAR–SAF group decreased after dietary reversal. The plasma biochemical profiles decreased in the LAR–SAF and SAF groups (P < 0.05) compared with those of the LAR group. The blood glucose level of the LAR–SAF group was reduced during intraperitoneal glucose tolerance test compared with that of the LAR group. The LAR–SAF group had lower levels of Orexin and Ghrelin gene expression, whereas the level of PPARa gene expression was significantly enhanced compared with that of the LAR group. So, the SAF diet can alter adipocytic adiposity-related gene expression and result in effective amelioration of diet-induced obesity.

To explore the efficacy and safety of expanding cytomegalovirus specific cytotoxic T lymphocytes (CMV-CTL) in vitro on refractory cytomegalovirus (CMV) infection.A total of twenty-eight patients with refractory CMV infection following stem cell transplant (SCT) were treated with CMV-specific T cells, of which 19 cases were from hematopoietic stem cell donors and 9 from third-party donors. In the first course, CTL was infused once or twice and the efficacy and adverse effects were evaluated. If CMV infection relapsed after complete remission (CR), the second course would be given.Twenty-one patients with refractory CMV viremia and seven with CMV diseases were eligible for adoptive T-cell transfer. After a median of 76 (39-321) days post-transplant, patients received a median dose of 1.0 (0.5-10.0) × 10(7) CTL infusion in the first course. All twenty-one patients with CMV viremia and four patients with CMV diseases achieved CR after using 9 (3-23) and 7 (4-18) days respecitvely. Six patients with CMV viremia and one with CMV disease received the second course after recurrence. Another four patients with viremia and one with CMV disease had reached CR again. Five patients exhibited graft-versus-host diseases (GVHD), all experiencing mild to moderate skin involvement. Six patients died of CMV infection and 2 of other transplantation-related complications.Our preliminary results have shown that CMV-CTL infusion is effective against refractory cytomegalovirus infection following SCT, but therapeutic schedule still needs to be improved in further study.

To improve the understanding of treatment for graft failure by analyzing the efficacy of second transplantation for graft failure after first allogeneic stem cell transplantation (allo-HSCT).Twenty-two patients encountered graft failure after first allo-HSCT from Peking University Institute of Hematology were retrospectively reviewed. The incidence of re-engratment, graft versus host disease (GVHD) and overall survival (OS) was analyzed. Also the factors associated with re-engraftment and OS were analyzed in multivariate model.Twenty-two patients encountered graft failure, including 12 primary graft failure and 10 secondary graft failure. 13(59.1%) patients acquired engraftment. And 13 patients acquired neutropil engraftment with median time of 15 (7-26) days, while 9 patients acquired platelet engraftment with median time of 12 (7-14) days. None of the factors included in mulivariate analysis showed impact on engraftment. The treatment related mortality at 100 day and 3 years after second transplantation was 40.9% and 72.7%, respectively. The main cause of death was infection (13/17). The 3-year OS was 22.7%, and the main cause of death was infection (13/17). The factors associated with OS included primary graft failure [P=0.001, HR 40.207 (4.828-334.868)] and receiving second transplantation in 60 days after first transplantation [P=0.003, HR 12.340 (2.290-66.498)].Second transplantation may be an effective salvage choice for graft failure. However, the efficacy was far from satisfactory.

To explore the incidence, influence factors and treatment methods of oral mucositis (OM) following hematopoietic stem cells transplantation (HSCT).A clinical analysis about the total 71 OM cases occurring after HSCT among 166 patients in Peking University People's Hospital during 2009 was completed.The healing rate of OM was 95.77% and the average healing time was (17.61 +/- 8.36) d after HSCT. There were no obvious effects of gender, age, HLA matches, conditioning regimen to the healing time of OM (P0.05).Gender, age, HLA matches and conditioning regimen have no obvious effects on healing time. By given timely and effective treatment, the incidence of OM can be reduced and even severe OM can also be well cured.

Apelin is secreted by adipocytes acting on APJ receptor and plays an important role in control of feeding behavior, energy expenditure, and the regulation of body fluid homeostasis. The adipokine is regulated by insulin and tumor necrosis factor-alpha in adipose tissue, suggesting apelin is involved in the regulation of pancreatic function. In this study, we incubated rat insulinoma INS-1 cells producing insulin for 60 min and examined the effects of pyr(1)-apelin-13 on insulin secretion and the mechanism.INS-1 cells were incubated in the presence of various concentrations of glucose and/or apelin, glucagon-like peptide-1 (GLP-1), phosphoinositide 3-kinase (PI3-kinase) inhibitor, phosphodiesterase 3B (PDE3B) inhibitor, and cAMP analogues. We examined the effect of apelin on insulin secretion and the pathway of the action. Insulin concentrations were measured by radioimmunoassay.We found that apelin over the concentration range of 1-10(4) nmol/L inhibited the insulin response to glucose and GLP-1 and the concentration effect was biphasic. The effect of apelin was abolished when insulin secretion was induced with cAMP analogues that cannot be hydrolyzed by cyclic nucleotide PDE3B. Selective inhibitors of PDE3B and PI3-kinase completely prevent the apelin effect on insulin secretion and cAMP accumulation.These findings suggest that apelin exerts direct inhibitory actions on the pancreatic beta-cells by activating PI3-kinase-dependent PDE3B and subsequently suppressing of cAMP levels.

To determine the direct effect of leptin on adipose tissue apoptosis in vitro using rat adipose-derived stem cells (ADSCs), we isolated the ADSCs of rat epididymis adipose tissue by collagenase digestion, filtration, and subsequent centrifugation. Cell cultures with or without leptin (10(-9) mol/L, 10(-8) mol/L, 10(-7) mol/L and 10(-6) mol/L) were incubated for different time. We examined the cell surface phenotype by immunofluorescence and detected the apoptosis morphological changes of ADSCs by laser scanning confocal microscope (LCSM). The number of apoptotic cells was determined by flow cytometry assay after annexin V binding and PI staining. Caspase-3 activity was measured by spectrofluorometry. The present study demonstrates that leptin treatment causes a marked increase in adipose-derived stem cell apoptosis. With the LCSM, after being treated with leptin, ADSCs showed the typical characteristic of apoptosis. Leptin in used concentrations (0 mol/L, 10(-8) mol/L, 10(-7) mol/L, 10(-6) mol/L) caused a marked increase in cell apoptosis after 48 h incubation time (for 2.50% +/- 0.72%, 6.78% +/- 1.99%, 11.99% +/- 1.58% and 17.93% +/- 4.82%, respectively, P0.05). Caspase-3 activity increased and reached a maximal level after 48 h in a linear fashion. The effect of leptin was dose-dependent and time-dependent. Leptin has been demonstrated to induce preadipocyte and adipocyte apoptosis, and today we demonstrate that leptin can induce ADSCs apoptosis, which can contribute to the decrease of adiposity. To our knowledge, this is the first study demonstrating the direct peripheral effect of leptin on ADSCs.