Effect of Multiple Coatings of One-step Self-etching Adhesive on Microtensile Bond Strength to Primary Dentin

Objective To investigate the effect of multiple coatings of the one-step self-etching adhesive on immediate microtensile bond strength to primary dentin.Methods Twelve caries-free human primary molars were randomly divided into 2 groups with 6 teeth each.In group 1,each tooth was hemisected into two halves.One half was assigned to control subgroup 1,which was bonded with a single-step self-etching adhesive according to the manufacturer's instructions;the other half was assigned to experimental subgroup 1 in which the adhesive was applied three times before light curing.In group 2,the teeth were also hemisected into two halves.One half was assigned to control subgroup 2,which was bonded with the single-step self-etching adhesive according to the manufacturer's instructions;the other half was assigned to experimental subgroup 2 in which three layers of adhesive were applied with light curing each successive layer.Microtensile bond strength was immediately tested after specimen preparation.Results When the adhesive was applied three times before light curing,the bond strength of the experimental subgroup 1(n=33,57.49±11.61 MPa) was higher than that of the control subgroup 1(n=31,49.71±11.43 MPa,P<0.05).When using the technique of applying multiple layers of adhesive with light curing each successive layer,no difference of immediate bond strength was observed between the control subgroup 2 and the experimental subgroup 2(P>0.05).Conclusion Multiple coatings of one-step self-etching adhesive can increase the immediate bond strength to primary dentin when using the technique of light-curing after applying three layers of adhesive.

Anti-BCMA CAR-T Cell Therapy in Relapsed or Refractory Multiple Myeloma Patients with Impaired Renal Function

Anti-B cell maturation antigen(BCMA)chimeric antigen receptor(CAR)T-cell therapyis effective and well-tolerated for refractory or relapsed multiple myeloma(RRMM).The purposcof the present study was to analyze efficacy in RRMM patients with renal impairment treated byanti-BCMA CAR-T cell therapy.A total of 59 RRMM patients were selected,and divided intoimpaired renal function(lRF)group[basclinc cstimated giomerular filtration rate(eSFR)<90 m/min/1.73 m^2(n=18)]and normal renal function(NRF)group(baseline eGFR≥90 mL/min/1.73 m,n=41).For patients with IRF,eGFR at the 6th month post-CAR-T cells infusion was significantlyhigher than the baseline(P<0.05).The multivariate analysis showed that light chain type and beta-2 micro-globulin(bcta-2M)were associated factors with the decrease of serum creatinine.Medianprogression-free survival(PFS)in the NRF group and IRF group was 266 days and 181 daysrespectively.Overall survival(OS)in the NRF group and lRF group was 877 days and 238 daysrespectively.There was no significant difference in the objective response rate(ORR)between thelRF group and the NRF group.It is suggested that CAR-T cells therapy could improve the renalfunction during the treatment of RRMM.The renal function could be more significantly improvedin RRMM patients with light chain type than with other types.

Analysis of WHO-Based Prognostic Scoring System(WPSS) of Myelodysplastic Syndrome and Its Comparison with International Prognostic Scoring System(IPSS) in 100 Chinese Patients

Objective： The aims of this study were to assess the prognostic significance of WHO-based Prognostic Scoring System （WPSS） in myelodysplastic syndrome （MDS） from a single center institute and to compare WPSS with the international prognostic scoring system （IPSS）. Methods： A total of 100 cases with de novo MDS were reviewed and their karyotypes were detected. All of them were followed up and classified according to IPSS and WPSS risk groups. SPSS 13.0 software was applied to deal with all the data. The statistical methods included Kaplan - Meier, Log-rank test and cox regression. Results： Multivariate cox regression analysis indicated that WHO Classification （P=0.0190）, karyotype abnormalities categorized according to IPSS （P=0.0159） and red blood cell （RBC） transfusion （P=0.0009） were the three most important independent factors for predicting overall survival （OS） of MDS. WPSS and IPSS both had great capacity in predicting the OS of MDS at the time of diagnosis （P〈0.0001）. In time-dependent analysis, WPSS can predict the OS accurately in the following three years after diagnosis （P〈0.0001）, while IPSS failed to predict the OS 24 months after diagnosis （P=0.1094）. Conclusion： Our single center results proved that WPSS is a dynamic prognostic system which can predict the OS of MDS patients at any time during the course of their disease. This time-dependent prognostic scoring system may replace the IPSS in the near future.

Inherited Genetic Susceptibility to Nonimmunosuppressed Epstein-Barr Virus-associated T/NK-cell Lymphoproliferative Diseases in Chinese Patients

Epstein-Barr virus(EBV)T/NK-cell lymphoproliferative diseases are characterized by clonal expansion of EBV-infected T or NK cells,including chronic active EBV infection of T/NK-cell type(CAEBVT/NK),EBV-associated hemophagocytic lymphohistiocytosis(EBV HLH),extranodal NK/T-cell lymphoma of nasal type(ENKTL),and aggressive NK-cell leukemia(ANKL).However,the role of inherited genetic variants to EBV+T/NK-LPDs susceptibility is still unknown.A total of 171 nonimmunosuppressed patients with EBV T/NK-LPDs and 104 healthy donors were retrospectively collected and a targeted sequencing study covering 15 genes associated with lymphocyte cytotoxicity was performed.The 94 gene variants,mostly located in UNCI 3D,LYST,ITK,and PRF1 genes were detected,and mutations covered 28/50(56.00%)of CAEBV-T/NK,31/51(60.78%)of EBV HLH,13/28(46.42%)of ENKTL,and 13/48(27.09%)of ANKL.Most mutations represented monoallelic and missense.Three-year overall survival rate of patients with CAEBV-T/NK and EBV+HLH was significantly lower in patients with germline mutations than in those without germline mutations(P=0.0284,P=0.0137).Our study provided novel insights into understanding a spectrum of nonimmunosuppressed EBV*T/NK-LPDs with respect to genetic defects associated with lymphocyte cytotoxicity and reminded us that the gene sequencing may be an auxiliary test for diagnosis and risk stratification of EBV+T/NK-LPDs.

CAR T Cell Therapy for Hematological Malignancies

As a rapidly progressing field in oncology,the adoptive transfer of T cells that have been genetically modified with chimeric antigen receptors(CARs)has shown striking efficacy in the management of hematological malignancies and has been reported in a number of clinical trials.of note,CAR T cell therapy has shown extraordinary potential,especially in relapsed/refractory patients.However,there are still challenges regarding the further development of this strategy,spanning from engineering and manufacturing issues,to limited applications,to accompanying toxicities.In this review,we will summarize the general knowledge of this novel method,including receptor composition,applications,adverse events and challenges.Additionally,we will propose several comprehensive recommendations.

Point source detection performance of Hard X-ray Modulation Telescope imaging observation

The Hard X-ray Modulation Telescope（HXMT） will perform an all-sky survey in the hard X-ray band as well as deep imaging of a series of small sky regions.We expect various compact objects to be detected in these imaging observations. Point source detection performance of HXMT imaging observation depends not only on the instrument but also on the data analysis method that is applied since images are reconstructed from HXMT observed data with numerical methods. The denoising technique used plays an important part in the HXMT imaging data analysis pipeline along with demodulation and source detection. In this paper we have implemented several methods for denoising HXMT data and evaluated the point source detection performances in terms of sensitivities and location accuracies. The results show that direct demodulation with 1-fold cross-correlation should be the default reconstruction and regularization method, although both sensitivity and location accuracy could be further improved by selecting and tuning numerical methods in data analysis used for HXMT imaging observations.

An accelerated direct demodulation method for image reconstruction using spherical data from the hard X-ray modulation telescope

The hard X-ray modulation telescope （HXMT） mission is mainly devoted to performing an all-sky survey at 1- 250 keV with both high sensitivity and high spatial resolution. The observed data reduction as well as the image reconstruction for HXMT can be achieved by using the direct demodulation method （DDM）. However the original DDM is too computationally expensive for multi-dimensional data with high resolution to be employed for HXMT data. We propose an accelerated direct demodulation method especially adapted for data from HXMT. Simulations are also presented to demonstrate this method.

Monitoring and Analysis of Chinese Chronic Myeloid Leukemia Patients Who Have Stopped Tyrosine Kinase Inhibitor Therapy

Discontinuation of tyrosine kinase inhibitor(TKI)therapy after achieving a persistent deep molecular response(DMR)is an urgently needed treatment goal for chronic myeloid leukemia(CML)patients and has been included in the National Comprehensive Cancer Network(NCCN)guidelines(version 2.2017)for CML.Indeed,various studies have confirmed the feasibility of discontinuing TKI therapy.In this study,we analyzed data from 45 CML patients who had discontinued TKI therapy.Univariate analysis was performed to predict factors that were potentially related to treatment-free remission(TFR)and identify the differences between early relapse and late relapse.Out of the 45 patients,20 exhibited molecular relapse after a median follow-up of 18 months(range,1-54 months),and the estimated TFR at 24 months was 40%.The univariate analysis revealed that a high Sokal score and interruptions or dose reductions during TKI treatment were the only baseline factors associated with poor outcomes.Our results indicate that TKI discontinuation could be successfully put into practice in China.

Multiple Coatings can Improve the Bond Durability of One-step Self-etching Adhesive to Primary Dentin

Objective To investigate whether multiple coatings can improve the bond durability of one-step self-etching adhesive to primary dentin.Methods Twelve caries-free human primary molars were randomly divided into 2 groups.In group 1,each tooth was hemisected into 2 halves.One half was assigned to the control subgroup 1,which was bonded with a commercially available one-step self-etching adhesive according to the manufacturer's instructions;the other half was assigned to experimental subgroup 1,in which the adhesive was applied three times before light curing.In group 2,one split half tooth was bonded with a commercially available one-step self-etching adhesive according to the manufacturer's instructions;for the other half,three layers of adhesive were applied with each successive layer of light curing.Specimens were stored in 0.9% NaCl containing 0.02% sodium azide at 37℃ for 18 months and then were subjected to microtensile bond strength test and the fracture mode analysis.Results When the adhesive was applied three times before light curing,the bond strength of the experimental subgroup 1 was significantly higher than that of the control subgroup 1(47.46±13.91 vs.38.12±11.21 MPa,P<0.05).When using the technique of applying multiple layers of adhesive with each successive layer of light curing,no difference was observed in bond strength between the control subgroup and the experimental subgroup(39.40±8.87 vs.40.87±9.33 MPa,P>0.05).Conclusion Multiple coatings can improve the bond durability of one-step self-etching adhesive to primary dentin when using the technique of light-curing after applying 3 layers of adhesive.

Timing analysis of the black hole candidate EXO 1846–031 with Insight-HXMT monitoring

We present the observational results from a detailed timing analysis of the black hole candidate EXO 1846-031 during its outburst in 2019 with the observations of Insight-HXMT,NICER and MAXI.This outburst can be classified roughly into four different states.Type-C quasi-periodic oscillations(QPOs)observed by NICER(about 0.1-6 Hz)and Insight-HXMT(about 0.7-8 Hz)are also reported in this work.Meanwhile,we study various physical quantities related to QPO frequency.The QPO rms-frequency relationship in the energy band 1-10 keV indicates that there is a turning pointing in frequency around2 Hz,which is similar to that of GRS 1915+105.A possible hypothesis for the relationship above may be related to the inclination of the source,which may require a high inclination to explain it.The relationships between QPO frequency and QPO rms,hardness,total fractional rms and count rate have also been found in other transient sources,which can indicate that the origin of type-C QPOs is non-thermal.

Elaiophylin triggers paraptosis and preferentially kills ovarian cancer drug-resistant cells by inducing MAPK hyperactivation

Finely tuned mitogen-activated protein kinase(MAPK)signaling is important for cancer cell survival.Perturbations that push cells out of the MAPK fitness zone result in cell death.Previously,in a screen of the North China Pharmaceutical Group Corporation’s pure compound library of microbial origin,we identified elaiophylin as an autophagy inhibitor.Here,we demonstrated a new role for elaiophylin in inducing excessive endoplasmic reticulum(ER)stress,ER-derived cytoplasmic vacuolization,and consequent paraptosis by hyperactivating the MAPK pathway in multiple cancer cells.Genome-wide CRISPR/Cas9 knockout library screening identified SHP2,an upstream intermediary of the MAPK pathway,as a critical target in elaiophylin-induced paraptosis.The cellular thermal shift assay(CETSA)and surface plasmon resonance(SPR)assay further confirmed the direct binding between the SHP2 and elaiophylin.Inhibition of the SHP2/SOS1/MAPK pathway through SHP2 knockdown or pharmacological inhibitors distinctly attenuated elaiophylin-induced paraptosis and autophagy inhibition.Interestingly,elaiophylin markedly increased the alreadyelevated MAPK levels and preferentially killed drug-resistant cells with enhanced basal MAPK levels.Elaiophylin overcame drug resistance by triggering paraptosis in multiple tumor-bearing mouse models resistant to platinum,taxane,or PARPi,suggesting that elaiophylin might offer a reasonable therapeutic strategy for refractory ovarian cancer.

Analysis on Surface Longitudinal Cracking of Q345D Slab

The surface longitudinal cracking of peritectic steel Q345 D slab was studied by means of metallographic microscopy and scanning electron microscopy. The results show that the surface longitudinal cracking is caused by the shell repeatedly tearing and healing under the action of stress, which is due to disruption of the steel matrix continuity with inclusion aggregation on the shell surface. The relative precautions of reducing the cracking are raised according to the practical situation.