Development of the neonatal pain response variable set: a mixed methods consensus process.

While over 40 neonatal pain assessment scales have been published, owing to a lack of consensus and standardized metrics, there are more than 100 assessment indicators with varying descriptors and quality differences. This study aims to reach a consensus on optimal and comprehensive variables for neonatal pain assessment, leading to the development of a multidimensional neonatal pain response variable set. This study consisted of three phases: (1) A literature review was conducted to identify influencing factors and assessment indicators of neonatal pain response. (2) Panel meetings involving neonatal healthcare professionals evaluated and screened factors and indicators to develop an initial draft of the variable set. (3) Through two rounds of Delphi study achieved consensus, and determined the neonatal pain response variable set. Through a literature review and a panel meeting, the identified factors and indicators were categorized into contextual, physiological, and behavioral variables, forming an initial draft of the variable set. Sixteen professionals participated in two rounds of the Delphi study, with response rates exceeding 70%, and authority coefficients surpassing 0.7 in both rounds. The final iteration of the variable set includes 9 contextual variables, 2 physiological variables, and 5 behavioral variables.   Conclusion: Neonatal pain response variable set developed in this study is scientific, comprehensive, and multidimensional, aligning with the characteristics of neonatal pain response and clinically applicable. The inclusion of contextual variables enhances the ability to confront the complexity of clinical environments and individual differences. It can provide a practical and theoretical basis for clinical research on neonatal pain assessment. What is Known: • Neonatal pain assessment relies on scales used by healthcare professionals currently. But there is no "gold standard" for neonatal pain assessment. • While over 40 neonatal pain assessment scales have been published, owing to a lack of consensus and standardized metrics, there are more than 100 assessment indicators with varying descriptors and quality differences. Most of scales overlook the clinical environment complexity individual differences in pain responses, diminishing the accuracy and applicability. What is New: • In addition to the commonly used physiological and behavioral variables in the scales, we have incorporated contextual variables to better address the complexity of clinical environments and individual differences in pain responses. • Through an evidence-based approach, developed a neonatal pain response variable set comprising 9 contextual variables, 2 physiological variables, and 5 behavioral variables.

[Effect of Chlorambucil Combined with Ibrutinib on Mantle Cell Lymphoma Cell Line Jeko-1 and Its Related Mechanism].

OBJECTIVE: To investigate the toxic effect of chlorambucil combined with ibrutinib on mantle cell lymphoma (MCL) cell line Jeko-1 and its related mechanism. METHODS: The MCL cell line Jeko-1 was incubated with different concentrations of chlorambucil or ibrutinib or the combination of the two drugs, respectively. CCK-8 assay was used to detect the proliferation of the cells, and Western blot was used to measure the protein expression levels of BCL-2, caspase-3, PI3K, AKT and P-AKT. RESULTS: After Jeko-1 cells were treated with chlorambucil (3.125, 6.25, 12.5, 25, 50 µmol/L) and ibrutinib (3.125, 6.25, 12.5, 25, 50 µmol /L) alone for 24, 48, 72h respectively, the cell proliferation was inhibited in a time- and dose-dependent manner. Moreover, the two drugs were applied in combination at low doses (single drug inhibition rate<50%), and the results showed that the combination of two drugs had a more significant inhibitory effect (all P < 0.05). Compared with the control group, the apoptosis rate of the single drug group of chlorambucil (3.125, 6.25, 12.5, 25, 50 µmol/L) and ibutinib (3.125, 6.25, 12.5, 25, 50 µmol/L) was increased in a dose-dependent manner. The combination of the two drugs at low concentrations (3.125, 6.25, 12.5 µmol/L) could significantly increase the apoptosis rate compared with the corresponding concentration of single drug groups (all P < 0.05). Compared with control group, the protein expression levels of caspase-3 in Jeko-1 cells were upregulated, while the protein expression levels of BCL-2, PI3K, and p-AKT/AKT were downregulated after treatment with chlorambucil or ibrutinib alone. The combination of the two drugs could produce a synergistic effect on the expressions of the above-mentioned proteins, and the differences between the combination group and the single drug groups were statistically significant (all P < 0.05). CONCLUSION: Chlorambucil and ibrutinib can promote the apoptosis of MCL cell line Jeko-1, and combined application of the two drugs shows a synergistic effect, the mechanism may be associated with the AKT-related signaling pathways.

A Novel Staggered Double-Segmented Grating Slow-Wave Structure for 340 GHz Traveling-Wave Tube.

In this paper, a novel staggered double-segmented grating slow-wave structure (SDSG-SWS) is developed for wide-band high-power submillimeter wave traveling-wave tubes (TWTs). The SDSG-SWS can be considered as a combination of the sine waveguide (SW) SWS and the staggered double-grating (SDG) SWS; that is, it is obtained by introducing the rectangular geometric ridges of the SDG-SWS into the SW-SWS. Thus, the SDSG-SWS has the advantages of the wide operating band, high interaction impedance, low ohmic loss, low reflection, and ease of fabrication. The analysis for high-frequency characteristics shows that, compared with the SW-SWS, the SDSG-SWS has higher interaction impedance when their dispersions are at the same level, while the ohmic loss for the two SWSs remains basically unchanged. Furthermore, the calculation results of beam-wave interaction show that the output power is above 16.4 W for the TWT using the SDSG-SWS in the range of 316 GHz-405 GHz with a maximum power of 32.8 W occurring at 340 GHz, whose corresponding maximum electron efficiency is 2.84%, when the operating voltage is 19.2 kV and the current is 60 mA.

The preparation and study on properties of calcium sulfate bone cement combined tuning silk fibroin nanofibers and vancomycin-loaded silk fibroin microspheres.

In this study, a bioactive composite material based on calcium sulfate hemihydrate (CSH) bone cement was studied, which use calcium sulfate dihydrate (CSD) as coagulant and silk fibroin nanofibers (SFF) solution as the curing liquid, further loaded vancomycin silk fibroin microspheres (SFM/VCM). The drug release effect of bone cements caused by tuning weight content of SFM/VCM (0.5, 1, 2%) and the concentration of silk fibroin solution (SFS) (20, 60, 100 mg/mL) used for preparation of SFM was studied in this article. Scanning electron microscope (SEM) demonstrated that the average diameter of microspheres gradually increased and the setting time was prolonged with the concentration of SFS increasing. X-ray diffraction (XRD) and Fourier transform infrared (FTIR) were used to analyze the composition of composite materials. The result of compressive strength revealed that the composites contained 0.5% SFM/VCM showed better mechanical performance independent on the concentration of microspheres and the cumulative drug release percentage of all composites were less than 55% after 4 weeks. The drug-loading bone cement possesses not only injectability but also sustained release capability which has a promising prospect in the field of bone substitute material.

Clinical characteristics and prognostic study of adult acute myeloid leukemia patients with ASXL1 mutations.

Objectives: A total of 156 adult acute myeloid leukemia (AML) patients were enrolled in this study to explore the clinical characteristics and prognostic impact of ASXL1 mutations. Methods: Clinical characteristics, prognostic impact and the association between ASXL1 mutations and some other mutations were analyzed. Results: We found ASXL1 mutations were most frequently found in M5 subtype and intermediate risk karyotype and were correlated with TET2, DNMT3A and PHF6 mutations. A total of 145 patients were included in prognostic analysis; results showed ASXL1 mutations had no impact on OS and DFS. In normal karyotype-AML (CN-AML) and older (≥60 years) AML, ASXL1 mutations showed adverse impact on OS (P = 0.022; p = 0.019, respectively) and showed adverse prognostic tendency on DFS (p = 0.173; p = 0.108, respectively). ASXL1 mutations were also independent unfavourable prognostic factors for OS on CN-AML and older (≥60 years) AML patients and unfavourable factors for DFS on older (≥60 years) AML in multivariate analysis. Results also indicated that though ASXL1 mutations were associated with TET2, DNMT3A and PHF6 mutations, when coinciding with ASXL1 mutations, the prognosis of AML was not significantly impacted. Discussion: The reliability of our results need to be further confirmed by prospective randomized controlled studies covering a large numbers of AML patients. Conclusion: The results showed ASXL1 mutations may act as a poor prognostic index especially in elder AML and CN-AML patients.

Lentivirus-mediated RNA interference targeting FAMLF-1 inhibits cell growth and enhances cell differentiation of acute myeloid leukemia partially differentiated cells via inhibition of AKT and c-MYC.

Genetic heterogeneity is the basis of clinical heterogeneity among different subtypes of AML. We have successfully cloned a gene related to AML termed FAMLF from a FAB-M2 patient's sample of a second largest AML pedigree. Then we revealed at least three splice variants, named as FAMLF-1, FAMLF-2 and FAMLF-3, and found miR181a1/b1 in the second intron of FAMLF gene family. Higher expression of FAMLF-1 was related to a higher complete remission (CR) rate, but shorter relapse free survival (RFS) in AML. We further found that the FAMLF-1 single nucleotide polymorphism (SNP) haplotype and its expression were positively correlated to clinical parameters of acute myeloid leukemia partially differentiated (FAB-M2) patients, but not FAB non-M2 patients or Acute Monocytic Leukemia (FAB-M5) patients. GTAGG SNP haplotype of FAMLF gene might increase FAB-M2 susceptibility in Han population and act as a useful candidate biomarker for FAB-M2 screening. We also demonstrated that FAMLF-1 gene silencing in FAB-M2 cells could lead to proliferation inhibition, cell cycle G0/G1 phase arrest, and differentiation promotion independent of its intronic miR-181a1, which might be related to Akt/c-Myc pathway. These findings reveal a role of FAMLF-1 as a potential pathogenic gene for FAB-M2.

C-Myc functions as a competing endogenous RNA in acute promyelocytic leukemia.

Recent reports have described a new post-transcriptional regulation that RNA transcripts can crosstalk with each other by competing for their common microRNAs. These RNA transcripts termed competing endogenous RNAs (ceRNAs) regulate the distribution of miRNAs on their targets. One corollary from ceRNA interaction is that chromosomal translocation in acute promyelocytic leukemia (APL) would perturb ceRNA regulation due to altered expression of 3'UTRs. In our study, we demonstrate that expression of PML/RARα, the APL-associated fusion oncogene is repressed by c-Myc mRNA transcript independent of protein-coding function but dependent upon microRNA. Attenuation of c-Myc transcript results in PML/RARα-degraded cellular phenotypes in APL cells, but these Myc reduction-associated cell phenotypes are sufficient to abrogate in a microRNA dependent manner. We also show that let-7 microRNA family members promote differentiation of All-Trans-Retinoic Acid (ATRA)-induced NB4 cells and their activities are affected by expression levels of both c-Myc and PML/RARα through altering miRNA targets. These results indicate that c-Myc mRNA represses PML/RARα expression via altering the distribution of let-7 miRNAs on their targets. Our findings reveal a previously unrecognized role of c-Myc as a potential ceRNA for PML/RARα in APL.

Prognostic significance of ASXL1 mutations in myelodysplastic syndromes and chronic myelomonocytic leukemia: A meta-analysis.

OBJECTIVES: Although additional sex comb-like 1 (ASXL1) gene mutations have long been reported in myelodysplastic syndromes (MDSs) and chronic myelomonocytic leukemia (CMML), the prognostic significance has been controversial. Therefore, a meta-analysis to study the impact of ASXL1 mutations on patients with MDS and CMML is useful. METHODS: The identified articles were retrieved from some common databases. We extracted hazard ratios (HRs) for overall survival (OS) and leukemic-free survival (LFS) and P-value of some clinical parameters, which compared AXSL1 mutations to those without from the available studies. Each individual HR and P-value was used to calculate the pooled HR and P-value. RESULTS: Six studies covering 1689 patients were selected for this meta-analysis. The pooled HRs for OS and LFS were 1.45 (95% confidential interval (CI), 1.24-1.70) and 2.20 (95% CI, 1.53-3.17), respectively. When considering CMML patients alone the HR for OS was 1.50 (95% CI, 1.18-1.90). Additionally, ASXL1 mutations were more frequently found in male (P = 0.008), older (P = 0.019), and patients with lower platelets (P = 0.009) or hemoglobin level (P = 0.0015) and associated with other mutations such as EZH2, IDH1/2, RUNX1, and TET2. DISCUSSION: Although our analysis has its limitation, it showed that ASXL1 mutations had significant inferior impact on OS and LFS for French-American-British-defined MDS patients. However, the influence of different types of ASXL1 mutations on patients with MDS still needs illustrating. CONCLUSION: ASXL1 mutations were associated with poor prognosis in MDS, which may contribute to risk stratification and prognostic assessment in the disease.