A prognostic model incorporating inflammatory cells and cytokines for newly diagnosed multiple myeloma patients.

Peripheral blood cell counts and cytokines can be used as predictors of multiple myeloma (MM) patients' outcomes. 313 newly diagnosed MM patients treated with novel agents were divided into training and validation cohorts. We selected the common peripheral blood cell counts, including the lymphocyte/monocyte ratio (LMR), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR), systemic inflammation response index (SIRI), and serum cytokines which contained tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-2 receptor (IL-2R), interleukin-8 (IL-8), interleukin-6 (IL-6), and interleukin-10 (IL-10) as related variables. The least absolute shrinkage and selection operator (LASSO) regression was conducted to sort the predictor variables in the training cohort, and then the developed nomogram was assessed in the training and validation cohort. Our study showed that SIRI, PLR, and IL-8 were independent prognostic factors for the survival of MM patients. Patients with lower SIRI (≤ 0.87) had superior survival than patients with higher SIRI (> 0.87). Further, according to the LASSO regression, a nomogram embracing LMR (> 3.78), SIRI (> 0.87), PLR (≤ 106.44), and IL-8 was established. The nomogram demonstrated a better correlation with the outcomes of MM patients in the training cohort than International Staging System (ISS) and Revised-International Staging System (R-ISS). The same results were verified in the validation cohort. The nomogram incorporating inflammatory cells and cytokines could be a helpful tool to stratify MM patients in the era of novel agents.

Single-Cell Transcriptomes Combining with Consecutive Genomics Reveal Clonal Evolution and Gene Regulatory Networks in Relapsed and Refractory Multiple Myeloma.

This study attempted to investigate how clonal structure evolves, along with potential regulatory networks, as a result of multiline therapies in relapsed/refractory multiple myeloma (RRMM). Eight whole exome sequencing (WES) and one single cell RNA sequencing (scRNA-seq) were performed in order to assess dynamic genomic changes in temporal consecutive samples of one RRMM patient from the time of diagnosis to death (about 37 months). The 63-year-old female patient who suffered from MM (P1) had disease progression (PD) nine times from July 2017 [newly diagnosed (ND)] to Aug 2020 (death), and the force to drive branching-pattern evolution of malignant PCs was found to be sustained. The mutant-allele tumor heterogeneity (MATH) and tumor mutation burden (TMB) initially exhibited a downward trend, which was then upward throughout the course of the disease. Various somatic single nucleotide variants (SNVs) that had disappeared after the previous treatment were observed to reappear in later stages. Chromosomal instability (CIN) and homologous recombination deficiency (HRD) scores were observed to be increased during periods of all progression, especially in the period of extramedullary plasmacytoma. Finally, in combination with WES and scRNA-seq of P1-PD9 (the nineth PD), the intro-heterogeneity and gene regulatory networks of MM cells were deciphered. As verified by the overall survival of MM patients in the MMRF CoMMpass and GSE24080 datasets, RUNX3 was identified as a potential driver for RRMM.

The paradoxical prognostic role of 1q21 Gain/Amplification in multiple myeloma: every coin has two sides.

The prognostic value of 1q21 Gain/Amplification (1q21 Gain/Amp) in multiple myeloma (MM) has always been controversial. A total of 419 newly diagnosed MM patients were included in this retrospective study. The positive rate of 1q21 Gain/Amp was 48.6%. MM patients with 1q21 Gain/Amp were characterized as being in more advanced clinical stages and were more likely to be accompanied by del(13q14), t(4;14) or complex karyotypes (CKs) as well as with more severe anemia and worse renal function. In these patients, the percentage of complete remission (CR) or very good partial response (VGPR) was higher, however, in the early treatment period, the probability of progressive disease (PD) was also higher. No significant difference on progression free survival (PFS) and overall survival (OS) was showed between the group of 1q21Amp and 1q21Gain. The prognostic impact of 1q21 Gain/Amp on PFS of MM patients was heterogeneous and was in accordance with the accompanying parameters.

rhTPO combined with chemotherapy and G-CSF for autologous peripheral blood stem cells in patients with refractory/relapsed non-Hodgkin's lymphoma.

OBJECTIVE: The mobilization and collection of sufficient autologous peripheral blood stem cells (APBSCs) are important for the fast and sustained reconstruction of hematopoietic function after autologous transplantation. This study aims to evaluate the mobilization effect and safety of thrombopoietin (TPO) combined with chemotherapy + G-CSF for APBSCs in patients with refractory/relapsed non-Hodgkin's lymphoma. METHODS: A total of 78 patients were included in the present study. After receiving mobilization chemotherapy, all patients were randomly divided into two groups: TPO group (n=40), patients were given subcutaneous injection of rhTPO + G-CSF, and control group (n=38), patients were given subcutaneous injection of G-CSF. The primary endpoint was the total number of obtained CD34+ cells. The secondary endpoints were the mononuclear cell count, the proportion of target and minimum mobilization, the engraftment time of neutrophils and platelets after APBSCT, the number of platelet and red blood cell infusions, the incidence of infectious fever and fever duration, and TPO-related side effects in patients. RESULTS: TPO participation significantly increased the total CD34+ cell count. A higher proportion of patients in the TPO group achieved the minimum and target CD34+ cells, when compared to the control group. TPO-related adverse events were not observed in either of these groups. In addition, there were no significant differences in engraftment time, the number of platelet and red blood cell transfusions, the incidence of infectious fever, and fever duration between these two groups. CONCLUSION: TPO combined with chemotherapy + G-CSF can safely and effectively enhance the mobilization effect for APBSCs in patients with refractory/relapsed non-Hodgkin's lymphoma.

Nonparaxial propagation of abruptly autofocusing circular Pearcey Gaussian beams.

We introduce a new class of abruptly autofocusing circular Pearcey Gaussian beams (AAFCPGBs) which tend to be abruptly autofocusing circular Pearcey beams with a small distribution factor, or Gaussian beams with a larger distribution factor. The nonparaxial propagation of the AAFCPGBs is investigated by numerical calculation. The radiation force of the AAFCPGBs exerted on a Rayleigh particle is analyzed in detail.

Focusing properties of circle Pearcey beams.

We introduce a new class of (2+1) dimensional circle Pearcey beams (CPBs) with the abruptly autofocusing (AAF) characteristics. Compared with circular Airy beams, CPBs can increase the peak intensity contrast, shorten the focus distance and, especially, eliminate the oscillation after the focal point. Furthermore, we discuss the influence of the optical vortices (including on-axis, off-axis, and vortex pairs) on the light intensity distribution of the CPBs during propagating.

Spatiotemporal Airy Ince-Gaussian wave packets in strongly nonlocal nonlinear media.

The self-accelerating Airy Ince-Gaussian (AiIG) and Airy helical Ince-Gaussian (AihIG) wave packets in strongly nonlocal nonlinear media (SNNM) are obtained by solving the strongly nonlocal nonlinear Schrödinger equation. For the first time, the propagation properties of three dimensional localized AiIG and AihIG breathers and solitons in the SNNM are demonstrated, these spatiotemporal wave packets maintain the self-accelerating and approximately non-dispersion properties in temporal dimension, periodically oscillating (breather state) or steady (soliton state) in spatial dimension. In particular, their numerical experiments of spatial intensity distribution, numerical simulations of spatiotemporal distribution, as well as the transverse energy flow and the angular momentum in SNNM are presented. Typical examples of the obtained solutions are based on the ratio between the input power and the critical power, the ellipticity and the strong nonlocality parameter. The comparisons of analytical solutions with numerical simulations and numerical experiments of the AiIG and AihIG optical solitons show that the numerical results agree well with the analytical solutions in the case of strong nonlocality.

Spatiotemporal sharply autofocused dual-Airy-ring Airy Gaussian vortex wave packets.

Here we investigate the propagation properties of spatiotemporal sharply autofocused single-Airy-ring Airy Gaussian vortex (AiRAiGV) and dual-Airy-ring Airy Gaussian vortex (dAiRAiGV) wave packets by solving the (3+1) D Schrödinger equation in free space. We can change the spatial part of the wave packets into Airy or Gaussian distribution by choosing the different spatial distribution factors bs. In particular, only when the shape of the pulses is set well with appropriate temporal distribution factor bt and initial velocity v in the temporal domain, dAiRAiGV wave packets can simultaneously autofocus in the spatial and temporal domains and the peak intensity is increased dozens of times at the focus more than that at the initial plane. Furthermore, properties of dAiRAiGV wave packets with a vortex in the center and off-axis vortex pairs are also discussed.

Propagation properties of spatiotemporal chirped Airy Gaussian vortex wave packets in a quadratic index medium.

A type of chirped Airy Gaussian vortex (CAiGV) localized wave packets in a quadratic index medium are studied by solving the paraxial differential equation. For the first time, the propagation properties of spatiotemporal CAiGV light bullets in the quadratic index medium are demonstrated. Some typical examples of the obtained solutions are based on the temporal and spatial chirp parameters, the initial velocity, the distribution factor, and the topological charge. The radiation force of the spatial CAiGV wave packet on a Rayleigh dielectric particle has the periodically reversion and recovery abilities due to the quadratic potential. What we report here can obtain different radiation force trajectory and may have potential application in optical tweezing and bio-medical field.

[A clinical comparative study on treatment of severe newly diagnosed immune thrombocytopenia by recombinant human thrombopoietin combined with glucocorticoid].

OBJECTIVE: To evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) combined with glucocorticoid in treatment of severe newly diagnosed primary immune thrombocytopenia (ITP). METHODS: From June 2009 to December 2012, 24 male patients and 38 female patients with the diagnosis of severe primary ITP in our hospital were randomized into trial group (31 cases) or control group (31 cases), the median age was 50 years (range: 21-84 years). Trial group was treated with rhTPO combined with glucocorticoid, and control group was treated with glucocorticoid only. RESULTS: At the day 3, 7 and 14 from the beginning of treatment, the average platelet count (APC) in trial group[(35.5±24.9)×109/L, (135.2±94.9)×109/L and (192.0±109.1)×109/L]were significantly higher than that in control group[(24.5±15.6)×109/L, (78.2±121.9)×109/L and (95.8±60.5)×109/L, P=0.022, 0.009 and 0.001, respectively]. There was no significant difference in APC between the two groups at day 28 and 90 after treatment[(147.8±59.1)×109/L vs (105.1±56.9)×109/L, P=0.243; (137.4±52.3)×109/L vs (104.3±59.8)×109/L, P=0.568, respectively]. At the day 7, 14 and 28, the complete response rates in trial group were 61.3%, 87.1% and 80.6%, which were also significantly higher than that in control group (16.1%, 29.0% and 48.3%, P=0.000, 0.000 and 0.004, respectively). The median time to response in trial group was 3 days while in the control group was 5 days; the median duration of complete response in trial group was 76 days while in the control group was 54 days. In trial group, there were 4 cases treated with platelet transfusion, while in control group there were 11 cases, respectively. CONCLUSION: For patients with severe primary ITP, rhTPO combined with glucocorticoid could rapidly increase the platelet count, significantly improve the complete response rate and prolonged the effect with a low incidence of tolerable adverse events compared to single use of glucocorticoid. rhTPO combined with glucocorticoid could be a new therapeutic choice to those patients.

Macrophage colony-stimulating factor expression in retrovirally transduced cells is dependent upon both the adherence status of the target cells and its 5' flanking untranslated region.

Numerous cell types retrovirally transduced with macrophage colony-stimulating factor (M-CSF) using LXSN-based vectors showed a variable expression of the transgene. Expression of M-CSF correlated with the cells' adherent status. Transduced adherent cells produced the M-CSF, whereas the non-adherent cells synthesized little M-CSF. Studies showed that the 5'-UTR of the M-CSF gene regulated transgenic M-CSF gene expression. Ligation of this 5'-UTR to the enhanced green fluorescent protein gene (EGFP) caused the expression of EGFP to show the same dichotomy as previously seen with the M-CSF. Transgenic M-CSF was expressed within non-adherent cells when the 5'-UTR was removed from the LXSN vector. Quantitative real-time polymerase chain reaction analysis confirmed that lesser production of M-CSF mRNA occurred within the non-adherent cells than in the adherent cells. This difference was eliminated when the 5'-UTR was removed from the retroviral vector. Our work suggests that this 5'-UTR of the M-CSF gene could be an important way to get transgenic expression within adherent cells, but not in non-adherent cells.

Antiangiogenic drugs synergize with a membrane macrophage colony-stimulating factor-based tumor vaccine to therapeutically treat rats with an established malignant intracranial glioma.

Combining a T9/9L glioma vaccine, expressing the membrane form of M-CSF, with a systemic antiangiogenic drug-based therapy theoretically targeted toward growth factor receptors within the tumor's vasculature successfully treated >90% of the rats bearing 7-day-old intracranial T9/9L gliomas. The antiangiogenic drugs included (Z)-3-[4-(dimethylamino)benzylidenyl]indolin-2-one (a platelet-derived growth factor receptor beta and a fibroblast growth factor receptor 1 kinase inhibitor) and oxindole (a vascular endothelial growth factor receptor 2 kinase inhibitor). A total of 20-40% of the animals treated with the antiangiogenic drugs alone survived, while all nontreated controls and tumor vaccine-treated rats died within 40 days. In vitro, these drugs inhibited endothelial cells from proliferating in response to the angiogenic factors produced by T9/9L glioma cells and prevented endothelial cell tubulogenesis. FITC-labeled tomato lectin staining demonstrated fewer and constricted blood vessels within the intracranial tumor after drug therapy. Magnetic resonance imaging demonstrated that the intracranial T9 glioma grew much slower in the presence of these antiangiogenic drugs. These drugs did not affect in vitro glioma cell growth nor T cell mitogenesis. Histological analysis revealed that the tumor destruction occurred at the margins of the tumor, where there was a heavy lymphocytic infiltrate. Real-time PCR showed more IL-2-specific mRNA was present within the gliomas in the vaccinated rats treated with the drugs. Animals that rejected the established T9/9L glioma by the combination therapy proved immune against an intracranial rechallenge by T9/9L glioma, but showed no resistance to an unrelated MADB106 breast cancer.