Advances in hematopoietic stem cells ex vivo expansion associated with bone marrow niche.

Hematopoietic stem cells (HSCs) are an ideal source for the treatment of many hematological diseases and malignancies, as well as diseases of other systems, because of their two important features, self-renewal and multipotential differentiation, which have the ability to rebuild the blood system and immune system of the body. However, so far, the insufficient number of available HSCs, whether from bone marrow (BM), mobilized peripheral blood or umbilical cord blood, is still the main restricting factor for the clinical application. Therefore, strategies to expand HSCs numbers and maintain HSCs functions through ex vivo culture are urgently required. In this review, we outline the basic biology characteristics of HSCs, and focus on the regulatory factors in BM niche affecting the functions of HSCs. Then, we introduce several representative strategies used for HSCs from these three sources ex vivo expansion associated with BM niche. These findings have deepened our understanding of the mechanisms by which HSCs balance self-renewal and differentiation and provided a theoretical basis for the efficient clinical HSCs expansion.

Arsenic trioxide replacing or reducing chemotherapy in consolidation therapy for acute promyelocytic leukemia (APL2012 trial).

As all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are widely accepted in treating acute promyelocytic leukemia (APL), deescalating toxicity becomes a research hotspot. Here, we evaluated whether chemotherapy could be replaced or reduced by ATO in APL patients at different risks. After achieving complete remission with ATRA-ATO-based induction therapy, patients were randomized (1:1) into ATO and non-ATO groups for consolidation: ATRA-ATO versus ATRA-anthracycline for low-/intermediate-risk patients, or ATRA-ATO-anthracycline versus ATRA-anthracycline-cytarabine for high-risk patients. The primary end point was to assess disease-free survival (DFS) at 3 y by a noninferiority margin of -5%; 855 patients were enrolled with a median follow-up of 54.9 mo, and 658 of 755 patients could be evaluated at 3 y. In the ATO group, 96.1% (319/332) achieved 3-y DFS, compared to 92.6% (302/326) in the non-ATO group. The difference was 3.45% (95% CI -0.07 to 6.97), confirming noninferiority (P < 0.001). Using the Kaplan-Meier method, the estimated 7-y DFS was 95.7% (95% CI 93.6 to 97.9) in ATO and 92.6% (95% CI 89.8 to 95.4) in non-ATO groups (P = 0.066). Concerning secondary end points, the 7-y cumulative incidence of relapse (CIR) was significantly lower in ATO (2.2% [95% CI 1.1 to 4.2]) than in non-ATO group (6.1% [95% CI 3.9 to 9.5], P = 0.011). In addition, grade 3 to 4 hematological toxicities were significantly reduced in the ATO group during consolidation. Hence, ATRA-ATO in both chemotherapy-replacing and -reducing settings in consolidation is not inferior to ATRA-chemotherapy (https://www.clinicaltrials.gov/, NCT01987297).

Mindful parenting and closeness in Chinese mother-adolescent dyads: The mediating role of adolescent self-disclosure.

Although having strong influences on adolescents' optimal development, mother-adolescent closeness is greatly challenged in early adolescence. Mindful parenting may be a protective factor for relational adjustment to early adolescence, but its connection with closeness within the mother-adolescent dyad has not been adequately examined in the literature. This study aimed to investigate the effects of how mindful parenting on the day-to-day mother-adolescent relationship dynamics, evaluating the relations between mindful parenting and mother-adolescent closeness and the mediating role of adolescent self-disclosure. A total of 76 Chinese mother-adolescent dyads completed a baseline measure of mindful parenting and 14-day measures of adolescent-report self-disclosure, mother-perceived closeness, and adolescent-perceived closeness. Mindful parenting significantly predicted both mother-perceived and adolescent-perceived closeness, with adolescent self-disclosure serving as a mediator. Adolescent self-disclosure predicted higher mother-adolescent closeness on the same day, but such effects did not carry over to the next day. Our findings provided evidence supporting mindful parenting as a resource for facilitating mother-adolescent closeness in early adolescence. This investigation also encouraged future studies to employ more intensive ambulatory assessments to clarify the daily process of how mindful parenting shapes mother-adolescent relationship dynamics.

The Association Between Mindful Parenting and Adolescent Internalizing and Externalizing Problems: The Role of Mother-Child Communication.

This study aimed to explore the mediation process from maternal mindful parenting to adolescent internalizing and externalizing problems through mother-child communication and adolescent self-disclosure. A total of 496 mother-adolescent dyads participated in the current study. Mother-reported mindful parenting and mother-child communication and adolescent-reported self-disclosure and behavior problems were collected. Path analysis results showed that mothers' mindful parenting was indirectly associated with adolescent internalizing and externalizing behaviors through mother-child communication and adolescent self-disclosure. In addition, the specific components of mindful parenting were examined in detail. The component of interacting with full attention showed unique patterns, while components of compassion and acceptance and emotion awareness of children showed similar pattern with the total score. These findings contribute to the knowledge of the mechanism underlying how mindful parenting benefit adolescent internalizing and externalizing behaviors, and have implications for clinical interventions.

A daily diary study of the relationships among daily self-compassion, perceived stress and health-promoting behaviours.

Previous studies consistently found that trait self-compassion is positively associated with health-promoting behaviours, and perceived stress mediates the relationship. The current study primarily aimed at examining whether state self-compassion varying from day to day (daily self-compassion) played the same role as trait self-compassion in improving health-promoting behaviours and whether or not perceived stress would be the mediator in this relationship. Eighty-nine Chinese employees were recruited to finish demographic information and the trait measure of self-compassion first, and then finish daily diaries for seven consecutive days. Daily diary measures included daily self-compassion, perceived stress and health-promoting behaviours including both eating behaviours and exercise behaviours. The results of 1-1-1 multilevel mediation analyses showed that, at both the within- and between-person level, daily self-compassion could positively predict daily eating behaviour through the reduction of perceived stress. However, daily self-compassion did not influence exercise behaviour at both levels. The results of 2-1-1 multilevel mediation analyses cross-validated the between-person relationships in the 1-1-1 multilevel mediation models. These results suggest that, both short-term interventions aiming at increasing state self-compassion and long-term interventions aiming at increasing trait self-compassion can benefit one's eating behaviours through the reduction of stress.

Resveratrol ameliorates cardiac dysfunction induced by pressure overload in rats via structural protection and modulation of Ca(2+) cycling proteins.

BACKGROUND: Cardiac hypertrophy is a compensatory stage of the heart in response to stress such as pressure overload (PO), which can develop into heart failure (HF) if left untreated. Resveratrol has been reported to prevent the development of hypertrophy and contractile dysfunction induced by PO. However, other studies found that resveratrol treatment for a longer period of time failed to regress cardiac hypertrophy. The aim of this study is to determine the timing of resveratrol treatment to achieve antihypertrophic effect and investigate whether resveratrol prevents the development of HF through preservation of myocardium structure and modulation of Ca(2+) handling proteins. METHODS: To generate rats with cardiac hypertrophy, male Sprague-Dawley rats were subjected to PO (aortic banding procedure) for 4 weeks. Sham-operated animals served as controls. Rats with cardiac hypertrophy were given resveratrol (4 mg/kg/day) for 4, 6, and 8 weeks, respectively. Histological and echocardiographic analysis and transmission electron microscopy were performed to assess cardiac structure and function. The levels of Ca(2+) handling proteins were measured by western blot analysis. RESULTS: Histological analysis showed that resveratrol treatment regressed developed cardiac hypertrophy at 8 and 10 weeks postsurgery, but not at 12 weeks. However, resveratrol strongly and continuously prevented the development of cardiac dysfunction and dilation of cardiac chamber as evaluated by echocardiography and H&E staining of heart cross-sections. In addition, PO-induced cardiac fibrosis was completely inhibited by resveratrol treatment. Resveratrol markedly prevented the disrupted myocardium but partially rescued mitochondrial abnormality in banded rats. Moreover, resveratrol prevented the alteration of Ca(2+) handling proteins induced by aortic banding, including downregulation of sarcoplasmic reticulum Ca(2+) ATPase 2 (SERCA2) and ryanodine receptor 2 (RyR2), hypophosphorylated phospholamban (PLB), upregulation of Na(+)/Ca(2+)-exchangers (NCX1) and increased expression and phosphorylation of Ca(2+)/calmodulin -dependent protein kinase II (CaMKII). Moreover, resveratrol alleviated the decreased SERCA activity induced by aortic banding. CONCLUSIONS: Resveratrol effectively prevented the transition from compensatory to decompensatory stage of cardiac hypertrophy induced by PO, but this effect is dependent on the timing of treatment. We suggest that resveratrol may exert beneficial effects on cardiac hypertrophy through protection of cardiac structure and modulation of Ca(2+) handling proteins.

[Construction of HSP47-shRNA and its impact on HSP47 at cellular level].

OBJECTIVE: To construct a short hairpin RNA (shRNA) against HSP47 gene, assess the expression level of HSP47 gene in NIH/3T3 cells, and observe the influence on cell function. METHODS: The HSP47-shRNA sequence presented at the downstream of the U6 promoter. The shRNA expression constructs were created using PCR- based methods. The PCR product was digested with Nhe I/Hind Ill and ligated into pGCsi/U6/Neo vector to produce HSP47-pGCsi-U6-shRNA (HSP47-1-pGCsi-U6-shRNA, HSP47-2-pGCsi-U6-shRNA and HSP47-3-pGCsi-U6-shRNA). The non-interference vector and non-related interference vector served as control. The vectors were transfected into NIH/3T3 fibroblast cells by liposome mediated gene transfection method. Transfection efficiency and fluorescence intensity were determined by fluorescence microscopy at 12, 24, 48, and 72 hours after transfection, respectively. Cells were collected before transfection, and at 24, and 48 hours post-transfection, respectively, HSP47 mRNA and protein expression levels were assessed by real-time PCR and Western blotting. The mRNA expression of TGF-pl, collagen types I and Ill in NIH/3T3 cells, and TGF-beta1 levels in cell culture supernatant were determined. RESULTS: HSP47-shRNA vector was transfected into NIH/3T3 cells by liposome-mediated transfection. The transfection efficiency in each HSP47-shRNA plasmid interference group was about 60.0%, and there is no statistical difference among the interference groups (P> 0.05). A small amount of green fluorescent cells were found at 12 h post-transfection. The number of green fluorescent cells increased with the transfection time, and reached strongest at 72 h after transfection. shRNA interference significantly inhabited HSP47 expression in NIHI/3T3 cells. At 24 h after transfection with HSP47-1-shRNA, the inhibition effect was the strongest, and the relative silence efficiency of HSP47 mRNA was (25.83?1.79)%, lower than that of control group and non-related group (P<0.05). Collagen synthesis and secretion by NIH/3T3 cells reduced significantly at 24 and 48 hours post-transfection with HSP47-1-shRNA; and there was a significant difference between HSP47-1-shRNA intervention group and non-related controls. After transfection for 24 and 48 h, mRNA expression of collagen types I and IlI decreased to (56.52 +/- 1.64)% and (53.48 +/- 2.54)%, (54.17 +/- 2.63)% and (50.21 +/- 2.34)%, respectively, significantly lower than that of the control group and non-related group (P<0.05); however, no significant difference was found among the interference groups (P>0.05). In each HSP47-shRNA plasmid interference group, TGF-p1 mRNA expression was the lowest at 24 h post-transfection. The relative mRNA expression level was (63.23?2.18)%, (64.5+3.17)%, and (75.19 +/- 4.20)% in HSP47-1-shRNA, HSP47-2-shRNA, HSP47-3-shRNA groups (P>0.05), respectively, lower than that of the control group and non-related group (P<0.01). At 24 and 48 h post-transfection, TGF-P131 expression was the lowest at 24 h post-transfection, and the relative expression level in HSP47-1-shRNA, HSP47-2-shRNA, HSP47-3-shRNA groups was (51.79 +/- 3.12)%, (66.67 +/- 2.13)%, and (69.61 +/- 3.65)%, respectively. Compared with control group, the expression of TGF-beta1 in HSP47-1-shRNA and HSP47-2-shRNA2 groups was significant inhibited, but there was no significantly difference between control group and HSP47-3-shRNA group (P>0.05). CONCLUSION: HSP47-shRNA. interference plasmid is constructed. HSP47-shRNA effectively inhibits protein expression of HSP47, and results in changes of cell function.

Immunophenotype of myeloid granulocytes in Chinese patients with BCR::ABL1-negative myeloproliferative neoplasms.

Typical BCR::ABL1-negative myeloproliferative neoplasms (MPN) are mainly referred to as polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofbrosis (PMF). Granulocytes in MPN patients are involved in their inflammation and form an important part of the pathophysiology of MPN patients. It has been shown that the immunophenotype of granulocytes in MPN patients is altered. We used flow cytometry to explore the immunophenotype of MPN patients and correlate it with clinical parameters. The results showed that PMF patients and PV patients had higher CD15+CD11b+ granulocytes than ET patients and normal controls. When grouped by gene mutation, changes in the granulocyte immunophenotype of MPN patients were independent of the JAK2V617F and CALR mutations. There was no significant heterogeneity in immunophenotype between ET patients and Pre-PMF, and between Overt-PMF and Pre-PMF patients. Granulocytes from some MPN patients showed an abnormal CD13/CD16 phenotype with a significant increase in mature granulocytes on molecular and cytomorphological grounds, and this abnormal pattern occurred significantly more frequently in PMF patients than in ET patients. CD15-CD11b- was negatively correlated with WBC and Hb and positively correlated with DIPSS score, whereas high CD10+ granulocytes were significantly and negatively associated with prognostic system IPSS and DIPSS scores in PMF patients. In conclusion, this study demonstrates the landscape of bone marrow granulocyte immunophenotypes in MPN patients. MPN patients, especially those with PMF, have a significant granulocyte developmental overmaturation phenotype. CD10+ granulocytes may be involved in the prognosis of PMF patients.

FSRW: fuzzy logic-based whale optimization algorithm for trust-aware routing in IoT-based healthcare.

The Internet of Things (IoT) is an extensive system of interrelated devices equipped with sensors to monitor and track real world objects, spanning several verticals, covering many different industries. The IoT's promise is capturing interest as its value in healthcare continues to grow, as it can overlay on top of challenges dealing with the rising burden of chronic disease management and an aging population. To address difficulties associated with IoT-enabled healthcare, we propose a secure routing protocol that combines a fuzzy logic system and the Whale Optimization Algorithm (WOA) hierarchically. The suggested method consists of two primary approaches: the fuzzy trust strategy and the WOA-inspired clustering methodology. The first methodology plays a critical role in determining the trustworthiness of connected IoT equipment. Furthermore, a WOA-based clustering framework is implemented. A fitness function assesses the likelihood of IoT devices acting as cluster heads. This formula considers factors such as centrality, range of communication, hop count, remaining energy, and trustworthiness. Compared with other algorithms, the proposed method outperformed them in terms of network lifespan, energy usage, and packet delivery ratio by 47%, 58%, and 17.7%, respectively.

Platelet Doubling After First Decitabine Cycle Predicts Response and Survival of Myelodysplastic Syndrome Patients.

OBJECTIVE: Although the effect of decitabine on myelodysplastic syndrome (MDS) has been demonstrated, merely a proportion of patients respond to therapy, and no well-recognized predictors have been identified. This study was conducted to investigate the effectiveness of decitabine in real-world clinical practice, and determine the predictive factors of response and overall survival (OS) in MDS patients. METHODS: Clinical and pathological data were collected from 94 patients and analyzed. These patients were reclassified according to the 2016 World Health Organization classification criteria, and restratified by International Prognostic Scoring System prognostic scores. The response evaluation was performed according to the 2006 modified International Working Group response criteria. RESULTS: In this study, 62% of patients responded to decitabine. Among these patients, 15 patients (16%) obtained complete remission (CR), 15 patients (16%) obtained marrow CR with hematologic improvement (HI), 20 patients (21%) obtained marrow CR without HI, and 8 patients (9%) only obtained HI, and no patient botained partial remission. The OS of the responders was significantly longer than that of non-responders (67 months vs. 7 months, P<0.001). The OS in patients with and without platelet doubling was significantly different in both the low/intermediate and high/very high risk groups (P=0.0398 and P=0.0330). The multivariate analysis revealed that platelet doubling after the first decitabine cycle is an independent predictor of response and OS in MDS patients (P=0.002 and P=0.008). CONCLUSION: Decitabine is effective for treating MDS patients in real-world clinical practice. Furthermore, platelet doubling after the first decitabine cycle can be used as a predictor of response and survival in MDS patients.

Evaluation of orelabrutinib monotherapy in patients with relapsed or refractory Waldenström's macroglobulinemia in a single-arm, multicenter, open-label, phase 2 study.

Background: Orelabrutinib is a novel, small molecule, selective irreversible Bruton tyrosine kinase inhibitor. The purpose of this study was to evaluate the efficacy and safety of orelabrutinib in patients with relapsed or refractory Waldenström's macroglobulinemia (R/R WM). Methods: This is a prospective, multicenter study of orelabrutinib in patients with WM who had at least one prior line of treatment. Orelabrutinib was administered orally at a daily dose of 150 mg until disease progression or unacceptable toxicity. The primary endpoint was major response rate (MRR) assessed by the Independent Review Committee (IRC) according to IWWM-6. This study is registered with ClinicalTrials.gov, NCT04440059. This trial was also registered on Center for Drug Evaluation (www.chinadrugtrials.org.cn) in March 2019, with a number of CTR2019036. Findings: Between August 2019 and December 2020, 66 R/R WM patients were assessed for eligibility. Forty-seven eligible patients were evaluated for efficacy at a median follow-up of 16.4 months (interquartile range: 12.5, 19.5). As assessed by IRC, the MRR was 80.9%, and the overall response rate was 89.4%. The median time to at least a minor response was 1.9 months. The PFS rates was 89.4% at 12 months. For patients with MYD88L265P /CXCR4NEG, MYD88L265P /CXCR4 S338X, and MYD88NEG /CXCR4NEG mutations, the MRRs were 84.6%, 100%, and 25.0%. Most adverse events were Grades 1 or 2 (91.0%). The common grade 3 or higher adverse events occurring were neutropenia (10.6%), thrombocytopenia (6.4%), and pneumonia (4.3%). Serious adverse events (SAE) occurred in 10 patients (21.3%). One treatment-related death was reported (hepatitis B reactivation). Interpretation: Orelabrutinib has shown good efficacy and manageable safety profiles in patients with R/R WM. Funding: InnoCare Pharma.

[The Inhibiting Effect of Autophagy Inhibitor ROC-325 on Multiple Myeloma].

OBJECTIVE: To investigate the effects of autophagy inhibitor ROC-325 and its combination with bortezomib on the proliferation, apoptosis and autophagy of multiple myeloma cell lines. METHODS: Multiple myeloma cells were treated with ROC-325 at different concentration. The cell proliferation was detected by CCK-8. Apoptosis was determined by Caspase-3/7 and Caspase-9 activity assays. Autophagy was detected by monodansylcadaverine staining. The apoptosis-related proteins (PARP and Caspase-3) and autophagy-related proteins (P62, Beclin-1, and LC3A/B) were analyzed by Western blot. The combined effect with bortezomib on bortezomib-resistant cell line was detected by CCK-8. RESULTS: ROC-325 inhibited the proliferation of RPMI 8226, RPMI 8226-BTZ100, U266 and IM9 cells in a dose-dependent manner (r=-0.8275, r=-0.9079, r=-0.9422, r=-0.9305), the 72 h IC50 values were 2.795, 4.020, 5.432 and 4.755 µmol/L, respectively. The activity assays of Caspase-3/7 and Caspase-9 showed that their relative activity was increased gradually in proportion to the drug concentration with the statistically significant difference (r=0.9648, r=0.9377, r=0.9318; r=0.9087, r=0.9431, r=0.8914). MDC staining results showed that the number of autophagic vacuoles increased with the rise of ROC-325 concentration (r=0.9565, r=0.9373, r=0.9233). ROC-325 could increase the expression of apoptosis-related proteins (PARP and Caspase-3) and autophagy-related proteins (P62 and LC3-Ⅱ/LC3-Ⅰ), but decrease the expression of Beclin-1 detected by Western blot. The CCK-8 assay showed that ROC-325 combined with bortezomib had synergistic effect on the inhibition of drug resistant cell line RPMI 8226-BTZ100. CONCLUSION: ROC-325 can inhibit the proliferation, induce the apoptosis of myeloma cells through the mitochondrial pathway, inhibit the autophagy of myeloma cells by affecting the fusion of autophagosomes and lysosomes, and overcome bortezomib resistance by the combination of ROC-325 with bortezomib.

Prognostic Value of D-Dimer in Patients with Diffuse Large B-cell Lymphoma: A Retrospective Study.

This study evaluated the significance of serum D-Dimer for predicting survival of patients with diffuse large B-cell lymphoma (DLBCL). We analyzed the clinical data from 113 patients who were newly diagnosed with DLBCL at Tongji Hospital from January 2012 to January 2016. The results indicated that there were higher levels of D-Dimer in DLBCL patients with the following characteristics: stage III/IV, lymphocyte monocyte ratio (LMR) <2.27, lactate dehydrogenase (LDH) > upper limit of normal (ULN), albumin (ALB) < 35 g/L, and anemia. After the first chemotherapeutic regimen, D-Dimer was significantly decreased concomitantly with LDH. Cox univariate regression analysis showed that the overall survival (OS) was negatively affected by the following factors: age > 60 years, stage III/W, LDH > ULN, LMR < 2.27, anemia and D-Dimer > 0.92. Multivariate analysis showed that only LDH > ULN (P=0.038) and age > 60 years (P=0.047) were independent adverse prognostic factors. However, it was suggested that D-Dimer could be regarded as a marker of high tumor burden and a potential prognostic screening tool for patients with DLBCL, not otherwise specified (NOS).

Clinical Features and MicroRNA Expression Patterns Between AML Patients With DNMT3A R882 and Frameshift Mutations.

Background: DNA methyltransferase 3A (DNMT3A) plays a unique role in hematopoiesis and acute myeloid leukemia (AML) pathogenesis. While the influences of DNMT3A mutation subtypes are still under debate. Purpose: Exploration of the clinical and molecular differences between AML patients carrying DNMT3A R882 mutations and DNMT3A frameshift mutations. Methods: Next generation of sequencing (NGS) and clinical data of 118 AML patients in our center were analyzed and compared. NGS, mRNA and miRNA profiling and clinical data from 12 patients in TCGA database were integrative analyzed. Results: Among all patients enrolled, 113 patients were positive for the variants of interest. Overall, a total of 295 variants were discovered, among which 24 DNMT3A mutations were detected, including 1 non-sense, 20 missense, 3 frameshift mutations. And 7 DNMT3A R882 mutations (3 R882H, 2 R882C, and 2 R882P) were found. Clinical analysis from our cohort and TCGA database indicated that patients carrying DNMT3A R882 mutation exhibited significantly higher levels of peripheral blood hemoglobin and non-significantly inferior prognosis compared with patients with DNMT3A frameshift mutations. Integrative analysis indicated that miR-10b, miR-143, and miR-30a were significantly decreased in the DNMT3A R882 group. High miR-143 expression is significantly associated with better prognosis in AML patients with DNMT3A mutations. Conclusion: Different molecular and clinical characteristics existed between patients with DNMT3A variant subtypes. The distinct microRNA expression pattern for DNMT3A R882 AML patients might not only act as markers to predict disease prognosis, but also could be further investigated to develop novel therapeutic targets for patients with DNMT3A mutations.

Remission of Microscopic Polyangiitis Using Traditional Chinese Medicine: A Case Report.

Microscopic polyangiitis (MPA) is a systemic disease described as necrotizing vasculitis that affects capillaries, venules and arterioles. Hormone-based immunosuppression therapy is the common treatment, but with severe side effects. Hence, non-hormone or low-hormone therapies may be another option. Here we report a case of a MPA patient, who was first diagnosed MPA at the age of 56, experienced a number of recurrences from 63 to 70 that were successfully controlled by Traditional Chinese Medicine (TCM) alone or with low-dose hormone.

Efficacy and Safety of Generic Dasatinib as a Second-line Treatment for Patients with Chronic Myeloid Leukemia: a Multicenter Retrospective Study in Hubei Province, China.

Dasatinib is a second-generation tyrosine kinase inhibitor (TKI) and it could be used as a second-line treatment for patients with chronic myeloid leukemia (CML). Yinishu, a generic dasatinib made in China, was approved by the China Food and Drug Administration in 2013 and it costs much less than the patented dasatinib SPRYCEL. The present study aimed to examine the efficacy and safety of Yinishu as a second-line treatment for CML by comparing the baseline clinical characteristics, rates of adverse events and efficacy between Yinishu and SPRYCEL groups. The results showed that there were no significant differences in the rates of optimal response between Yinishu and SPRYCEL for patients who started second-line treatment because of treatment failure. For patients who started second-line treatment because of intolerance of first-line treatment, their levels of BCR-ABL1/ABL1 on the international scale (BCR-ABLIS) was maintained very low throughout the course of Yinishu treatment. Drug-related adverse events occurred with the same frequency in these two groups. It was confirmed that Yinishu was effective and safe as a secondline treatment for CML patients. Yinishu may be more suitable for patients who are economically unable to pay for the patented dasatinib SPRYCEL.

Targeted Synthesis of Unique Nickel Sulfide (NiS, NiS2) Microarchitectures and the Applications for the Enhanced Water Splitting System.

Water splitting is one of the ideal technologies to meet the ever increasing demands of energy. Many materials have aroused great attention in this field. The family of nickel-based sulfides is one of the examples that possesses interesting properties in water-splitting fields. In this paper, a controllable and simple strategy to synthesize nickel sulfides was proposed. First, we fabricated NiS2 hollow microspheres via a hydrothermal process. After a precise heat control in a specific atmosphere, NiS porous hollow microspheres were prepared. NiS2 was applied in hydrogen evolution reaction (HER) and shows a marvelous performance both in acid medium (an overpotential of 174 mV to achieve a current density of 10 mA/cm2 and the Tafel slope is only 63 mV/dec) and in alkaline medium (an overpotential of 148 mV to afford a current density of 10 mA/cm2 and the Tafel slope is 79 mV/dec). NiS was used in oxygen evolution reaction (OER) showing a low overpotential of 320 mV to deliver a current density of 10 mA/cm2, which is meritorious. These results enlighten us to make an efficient water-splitting system, including NiS2 as HER catalyst in a cathode and NiS as OER catalyst in an anode. The system shows high activity and good stabilization. Specifically, it displays a stable current density of 10 mA/cm2 with the applying voltage of 1.58 V, which is a considerable electrolyzer for water splitting.

Inhibition of NF-kappaB by mutant IkappaBalpha enhances TNF-alpha-induced apoptosis in HL-60 cells by controlling bcl-xL expression.

BACKGROUND: The aim of this study was to explore whether the inhibition of nuclear factor-kappaB (NF-kappaB) activation by mutant IkappaBalpha (S32, 36-->A) can enhance TNF-alpha-induced apoptosis of leukemia cells and to investigate the possible mechanism. METHODS: The mutant IkappaBalpha gene was transfected into HL-60 cells by liposome-mediated techniques. G418 resistant clones stably expressing mutant IkappaBalpha were obtained by the limiting dilution method. TNF-alpha-induced NF-kappaB activation was measured by electrophoretic mobility shift assay (EMSA). The expression of bcl-xL was detected by RT-PCR and Western blot after 4 hours exposure of parental HL-60 and transfected HL-60 cells to a variety of concentrations of TNF-alpha. The percentage of apoptotic leukemia cells was evaluated by flow cytometry (FCM). RESULTS: Mutant IkappaBalpha protein was confirmed to exist by Western blot. The results of EMSA showed that NF-kappaB activation by TNF-alpha in HL-60 cells was induced in a dose-dependent manner, but was almost completely inhibited by mutant IkappaBalpha repressor in transfected cells. The levels of bcl-xL mRNA and protein in HL-60 cells increased after exposure to TNF-alpha, but changed very little in transfected HL-60 cells. The inhibition of NF-kappaB activation by mutant IkappaBalpha enhanced TNF-alpha-induced apoptosis. The cytotoxic effects of TNF-alpha were amplified in a time- and dose-dependent manner. CONCLUSIONS: NF-kappaB activation plays an important role in the resistance to TNF-alpha-induced apoptosis. The inhibition of NF-kappaB by mutant IkappaBalpha could provide a new approach that may enhance the anti-leukemia effects of TNF-alpha or even of other cytotoxic agents.

[Continuous veno-venous hemofiltration in treatment of severe acute pancreatitis].

OBJECTIVE: To observe the efficacy of continuous veno-venous hemofiltration (CVVH) in the treatment of severe acute pancreatitis (SAP). METHODS: Fifty three patients with SAP were involved, CVVH was performed for at least 24 hours. During CVVH, the patients' conditions and pancreatic enzymes (amylase and lipase) were observed, serum concentration of endotoxin was measured as well. RESULTS: After CVVH, the symptoms of patients such as tachycardia, respiratory distress, and abdominal pain were remitted. The APACHE II score decreased significantly. Six hours after CVVH, serum concentration of endotoxin was decreased significantly. Fifteen patients died, the mortality rate was 28.3%. CONCLUSION: CVVH could decrease the mortality rate of SAP with multiple organ dysfunction syndrome.