Validation and comparison of 5th edition World Health Organization classification (WHO 2022) and International Consensus Classification proposals for MDS-SFB31.

The criteria of myelodysplastic syndromes (MDS) with mutated SFB31 (MDS-SFB31) proposed by the 5th edition of the WHO classification (WHO 2022) and the International Consensus Classification (ICC) need validation. We analysed 125 consecutive MDS cases with SFB31 mutation or ring sideroblasts (RS) ≥15% without excess blasts. We found that SFB31-negative MDS with RS had significantly different clinical features and worse prognosis. According to WHO 2022, the detection of ≥15% RS may substitute for SF3B1 mutation and our analyses support this proposal for similar prognosis of two groups after excluding high-risk genetic features referred by WHO 2022. Patients with variant allele frequency (VAF) <10% SFB31 tend to have briefer survival, supporting the VAF 10% threshold of ICC. Patients with multilineage dysplasia (MLD) had significantly shorter OS than those with single lineage dysplasia. MLD is still a powerful morphological marker of worse outcome in WHO 2022 and ICC-defined MDS-SF3B1.

High energy barrier hydroxyl radical dissociation mechanism of a low shock sensitivity dihydroxylammonium 5,5'-bistetrazole-1,1'-diolate (TKX-50) explosive.

As a representative of the new generation of high-energy explosives, TKX-50 has attracted widespread attention due to its remarkably low sensitivity toward shock. However, the reported decomposition barriers of TKX-50 (∼37 kcal mol-1) are comparable to those of commonly used explosives. The mechanism of its low shock sensitivity remains unclear. In this study, using an ab initio molecular dynamics method combined with a multiscale shock simulation technique and transition state calculations (at the B2PLYP-D3/Def2TZVP level), we discovered an unconventional reaction pathway of TKX-50 under shock, and its rate-controlling step is the dissociation of the hydroxyl radical (OH) from the anion ring after proton transfer, followed by ring rupture and the production of H2O and N2. The barrier for this OH dissociation reaction is as high as 51.9 kcal mol-1. In contrast, under thermal stimuli, TKX-50 prefers to open rings directly after proton transfer without losing the OH. The corresponding barrier is 35.4 kcal mol-1, which is in good agreement with previous studies. The reason for the unconventional reaction pathway of TKX-50 under shock may be the suppression of anion ring opening in thermal decomposition by steric hindrance upon shock compression. In addition, the dominant N2 generation pathway under shock releases less energy than pyrolysis which further explains the low shock sensitivity of TKX-50. This study comprehensively elucidates the different reaction mechanisms of TKX-50 under thermal and shock conditions and proposes a crucial reaction pathway leading to its low shock sensitivity. These findings will contribute to the understanding and application of tetrazole anionic energetic salts.

Electroacupuncture combined with wet compress formula ameliorates upper limb dysfunction associated with stroke: A retrospective analysis of 126 cases.

OBJECTIVES: Upper limb motor dysfunction (ULMD) is one of the most common complications of ischemic stroke (IS). Electroacupuncture (EA) is a noninvasive procedure that has the potential to manage symptoms associated with IS. To improve the treatment effects of EA, our hospital performed combined treating strategy against ULMD by subjecting IS patients to both EA and external application of wet compress formula (WCF). In the current analysis, the potential improving effects of the combined treatment against ULMD were evaluated. MATERIALS AND METHODS: 126 patients with ULMD induced by IS handled with normal rehabilitation treatment, EA treatment alone, and EA combined with WCF respectively were enrolled in the current analysis. The clinicopathological information and changes in motor function assessment scales, including Visual analogue (VAS), Fugl-Meyer assessment-upper extremity (FMA-UA), and Modified Barthel index (MBI) scales were collected and the difference between different treating strategies was assessed. RESULTS: All the treating strategies improved the values of VAS, FMA-UA, and MBI scales, with combined treating strategy showing the strongest improving effects, and traditional rehabilitation strategy showing the weakest effects. Moreover, the assessment of hand and wrist motor function by FMA-UE also showed that the combined treatment strategy has significantly stronger improving effects against ULMD compared with other strategies. CONCLUSIONS: The current analysis showed that the use of external application of WCF could substantially increase the treating effects of EA on ULMD induced by IS without severe side effects, which could guide the future clinical management of motor dysfunction.

Integrated analysis of single-cell and bulk RNA sequencing identifies a signature based on macrophage marker genes involved in prostate cancer prognosis and treatment responsiveness.

In the tumor microenvironment, tumor-associated macrophages (TAMs) interact with cancer cells and contribute to the progression of solid tumors. Nonetheless, the clinical significance of TAM-related biomarkers in prostate cancer (PCa) is largely unexplored. The present study aimed to construct a macrophage-related signature (MRS) for predicting PCa patient prognosis based on macrophage marker genes. Six cohorts comprising 1056 PCa patients with RNA-Seq and follow-up data were enrolled. Based on macrophage marker genes identified by single-cell RNA-sequencing (scRNA-seq) analysis, univariate analysis, least absolute shrinkage and selection operator (Lasso)-Cox regression, and machine learning procedures were performed to derive a consensus MRS. Receiver operating characteristic curve (ROC), concordance index, and decision curve analyses were used to confirm the predictive capacity of the MRS. The predictive performance of the MRS for recurrence-free survival (RFS) was stable and robust, and the MRS outperformed traditional clinical variables. Furthermore, high-MRS-score patients presented abundant macrophage infiltration and high-expression levels of immune checkpoints (CTLA4, HAVCR2, and CD86). The frequency of mutations was relatively high in the high-MRS-score subgroup. However, the low-MRS-score patients had a better response to immune checkpoint blockade (ICB) and leuprolide-based adjuvant chemotherapy. Notably, abnormal ATF3 expression may be associated with docetaxel and cabazitaxel resistance in PCa cells, T stage, and the Gleason score. In this study, a novel MRS was first developed and validated to accurately predict patient survival outcomes, evaluate immune characteristics, infer therapeutic benefits, and provide an auxiliary tool for personalized therapy.

Impact of the International Consensus Classification of myelodysplastic syndromes.

The impact of the 2022 International Consensus Classification (ICC) of myelodysplastic syndromes (MDS) needs study. We analysed data from 989 MDS subjects classified using the 2016 World Health Organization (WHO) criteria to determine the impact of the new proposal. Our analyses suggested the ICC criteria of MDS-SF3B1 identifies a more homogenous disease entity than the WHO 2016 criteria of myelodysplastic syndromes with ring sideroblasts (MDS-RS). MDS, not otherwise specified with single lineage dysplasia (MDS, NOS-SLD) patients had a better prognosis than MDS, NOS with multilineage dysplasia (MDS, NOS-MLD) patients. MDS with mutated TP53 and MDS/acute myeloid leukaemia with mutated TP53 patients had the briefest survivals. These data support the ICC of MDS, which allows more accurate diagnoses and risk stratification.

ASXL1 mutations accelerate bone marrow fibrosis via EGR1-TNFA axis-mediated neoplastic fibrocyte generation in myeloproliferative neoplasms.

Apart from the central role of the activated JAK/STAT signaling pathway, ASXL1 mutations are the most recurrent additional mutations in myeloproliferative neoplasms and occur much more commonly in myelofibrosis than in essential thrombocythemia and polycythemia vera. However, the mechanism of the association with ASXL1 mutations and bone marrow fibrosis remains unknown. Here, integrating our own data from patients with myeloproliferative neoplasms and a hematopoietic-specific Asxl1 deletion/Jak2V617F mouse model, we show that ASXL1 mutations are associated with advanced myeloproliferative neoplasm phenotypes and onset of myelofibrosis. ASXL1 mutations induce skewed monocyte/macrophage and neoplastic monocyte-derived fibrocyte differentiation, consequently they enhance inflammation and bone marrow fibrosis. Consistently, the loss of ASXL1 and JAK2V617F mutations in hematopoietic stem and progenitor cells leads to enhanced activation of polycomb group target genes, such as EGR1. The upregulation of EGR1, in turn, accounts for increased hematopoietic stem and progenitor cell commitment to the monocyte/macrophage lineage. Moreover, EGR1 induces the activation of TNFA and thereby further drives the differentiation of monocytes to fibrocytes. Accordingly, combined treatment with a TNFR antagonist and ruxolitinib significantly reduces fibrocyte production in vitro. Altogether, these findings demonstrate that ASXL1 mutations accelerate fibrocyte production and inflammation in myeloproliferative neoplasms via the EGR1-TNFA axis, explaining the cellular and molecular basis for bone marrow fibrosis and the proof-ofconcept for anti-fibrosis treatment.

Reaction mechanism and electronic properties of host-guest energetic material CL-20/HA under high pressure by quantum-based molecular dynamics simulations.

The novel host-guest material 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20)/hydroxylamine (HA) improves the detonation energy of CL-20 explosives without compromising its safety. However, the reaction mechanism of CL-20/HA under high pressure is not yet fully understood for the complex host-guest structure. A multiscale shock simulation technique by quantum-based molecular dynamics was performed to investigate the reaction mechanism of CL-20/HA under shock with different velocities along different directions, focusing on charge transfer, electronic properties, reaction path and product evolution. The structural changes caused by both insertion of HA and charge overlap between CL-20 and HA are responsible for the electronic changes and gap decrease. Directional charge transfer was observed between CL-20 and HA molecular fragments during shock in all shock loading directions, causing the CL-20 molecular group to become electrically non-neutral. The C-N bond in the CL-20 cage then broke, leading to the release of nitro and nitrous oxide at high temperatures and pressures. The HA molecules or free H atoms from HA could bond with the O atom in the nitro group, leading to the N-O bond cleavage. Some free H atoms could act as an intermediary, connecting two CL-20 molecules and forming dimeric molecules briefly. Compared with the pure CL-20 system, HA can inhibit the reaction of CL-20 in the CL-20/HA system to some extent during the initial shock stage. A further understanding of the chemical reaction mechanism and energy release in dense host-guest materials can be advanced by focusing on the microscopic internal effects of the guest molecule on the host molecule reactions.

Machine learning quantitatively characterizes the deformation and destruction of explosive molecules.

Although explosives have been widely used in mines, road development, old building demolishing, and munition explosions; currently, how chemical bonds between atoms break and recombine, how the molecular structure is deformed and destroyed, how the reaction product molecules are formed, and the details for this rapid change process in explosive reactions are not yet fully understood, which limits the full use of explosive energy and safer use of explosives. This paper presents a quantitative model of molecular structure deformation using machine learning algorithms as well as a qualitative model of its relationship with molecular structure destruction, based on a molecular dynamics simulation and detailed analysis of the shock-loaded ε-CL-20, providing new perspectives for explosive community research. Specifically, the quantitative model of molecular structure deformation establishes the quantitative relationship between the molecular volume change and molecular position change, and between molecular distance change and molecular volume change using the machine learning algorithms such as Delaunay triangulation, clustering, and gradient descent. We find that the molecular spacing in explosives is strongly compressed after being shocked, and the peripheral structure can shrink inward, which is beneficial to keep the cage structure stable. When the peripheral structure is compressed to a certain extent, the cage structure volume begins to expand and is then destroyed. In addition, hydrogen atom transfer occurs within the explosive molecule. This study amplifies the structural changes and the chemical reaction process for explosive molecules after being strongly compressed by a shock wave, which can enrich the knowledge of the real detonation reaction process. The analysis method based on quantitative characterization using machine learning proposed in this study can also be used to analyze the microscopic reaction mechanism in other materials.

Ruxolitinib combined with prednisone, thalidomide and danazol in patients with myelofibrosis: Results of a pilot study.

Ruxolitinib is a safe and effective therapy of myeloproliferative neoplasm-associated (MPN) myelofibrosis. However, often there are dose reductions and/or therapy interruptions because of therapy-related adverse events (AEs), especially anemia and thrombocytopenia. We previously reported combined therapy with prednisone, thalidomide and danazol (PTD) reversed anemia and thrombocytopenia in people with MPN-associated myelofibrosis. We wondered whether adding PTD to ruxolitinib might mitigate the hematologic AEs and thereby avoid the dose reduction of ruxolitinib and improve the efficacy. To test this hypothesis, we conducted a baseline hemoglobin and platelet concentration assignment prospective observational study in 72 patients comparing 3-month dose adjustment and efficacy of ruxolitinib with (N = 53, the study group) or without (N = 19, the control group) PTD. According to the platelet counts, the median daily ruxolitinib doses in the study group increased from 30 to 40 mg by week 12, whereas in the control group it remained at 30 mg (p = 0.019). In the study group 35 patients had a hemoglobin increase ≥10 g/L compared with no patient receiving ruxolitinib only (p < 0.001). Platelet increases >100 × 10E+9/L were seen in 56.6% and 5.3% of patients in the two groups, respectively (p < 0.001). In patients with anemia and thrombocytopenia, 18 patients in the study group had an anemia response at week 12 and 12 had a platelet increase of ≥50 × 10E+9/L. No patient in the control group achieved either response (p < 0.001 and p = 0.078). The study group had a more spleen response than the control group (p = 0.046). Peripheral edema and transaminase elevation were the main nonhematologic AEs of PTD. These AEs can be alleviated by adjusting the danazol dose. In conclusion, adding PTD to ruxolitinib improved ruxolitinib-associated anemia and thrombocytopenia, and resulted in a higher ruxolitinib dose.

Reaction mechanism of aluminum nanoparticles in explosives under high temperature and high pressure by shock loading.

Aluminum nanoparticles (ANPs) can greatly improve the power of explosives. However, the rapid reaction mechanism of ANPs under simultaneous high temperature and high pressure by shock loading is not fully understood. In this study, a detonation wave was generated by impact of an explosive supercell on the reflect wall, and the reflected wave was eliminated by changing the end-boundary velocity. In this way, the problem of long time simulation under extreme pressure was solved and reaction molecular dynamics simulations of ANPs in explosives under shock or detonation were then performed with the ReaxFF force field. The results showed that the ANP crystal structure first transformed under shock loading, and diffusion oxidation of the ANPs then occurred. The reaction rate of the ANPs under high-temperature and high-pressure conformed to an exponential function of the pressure and oxide-shell thickness. Finally, the ANPs were stretched and disintegrated with expansion of the detonation products, which further accelerated ANP oxidation. A thicker oxide shell and a wax covering on the ANPs limited diffusion of the O and N atoms into the ANPs, which slowed down the oxidation reaction of the ANPs. A wax covering also prevented direct contact of the ANPs with the explosive, weakening the effect of the ANPs on the reaction of the explosive. This work is of great importance to deeply understand the reaction mechanism and energy-release law of aluminized explosives.

Insulator Umbrella Disc Shedding Detection in Foggy Weather.

The detection of insulator umbrella disc shedding is very important to the stable operation of a transmission line. In order to accomplish the accurate detection of the insulator umbrella disc shedding in foggy weather, a two-stage detection model combined with a defogging algorithm is proposed. In the dehazing stage of insulator images, solving the problem of real hazy image data is difficult; the foggy images are dehazed by the method of synthetic foggy images training and real foggy images fine-tuning. In the detection stage of umbrella disc shedding, a small object detection algorithm named FA-SSD is proposed to solve the problem of the umbrella disc shedding occupying only a small proportion of an aerial image. On the one hand, the shallow feature information and deep feature information are fused to improve the feature extraction ability of small targets; on the other hand, the attention mechanism is introduced to strengthen the feature extraction network's attention to the details of small targets and improve the model's ability to detect the umbrella disc shedding. The experimental results show that our model can accurately detect the insulator umbrella disc shedding defect in the foggy image; the accuracy of the defect detection is 0.925, and the recall is 0.841. Compared with the original model, it improved by 5.9% and 8.6%, respectively.

The Anisotropic Chemical Reaction Mechanism of 1,3,3-trinitroazetidine (TNAZ) under Different Shock Wave Directions by ReaxFF Reactive Molecular Dynamics Simulations.

1,3,3-Trinitroazetidine (TNAZ) has good thermal stability and low shock sensitivity, among other properties, and it has broad prospects in insensitive ammunition applications. In this study, a molecular dynamics calculation based on the ReaxFF-lg force field and multiscale shock technique (MSST) was used to simulate the shock-induced chemical reaction of TNAZ with different shock wave directions. The results showed that the shock sensitivity of TNAZ was in the order of [100] > [010] > [001]. There were significant differences in molecular arrangements in different shock directions, which affected the reaction rate and reaction path in different directions. The molecular arrangement in the [010] and [001] directions formed a "buffer" effect. The formation and cleavage of bonds, formation of small molecules and growth of clusters were analyzed to show the effect of the "buffer". The polymerization reactions in the [010] and [001] directions appeared later than that in the [100] direction, and the cluster growth in the [010] and [001] directions was slower than that in the [100] direction. In different shock loading directions, the formation and cleavage mechanisms of the N-O bonds of the TNAZ molecules were different, which resulted in differences in the initial reaction path and reaction rate in the three directions

Recent Progress on Synthesis, Characterization, and Performance of Energetic Cocrystals: A Review.

In the niche area of energetic materials, a balance between energy and safety is extremely important. To address this "energy-safety contradiction", energetic cocrystals have been introduced. The investigation of the synthesis methods, characteristics, and efficacy of energetic cocrystals is of the utmost importance for optimizing their design and development. This review covers (i) various synthesis methods for energetic cocrystals; (ii) discusses their characteristics such as structural properties, detonation performance, sensitivity analysis, thermal properties, and morphology mapping, along with other properties such as oxygen balance, solubility, and fluorescence; and (iii) performance with respect to energy contents (detonation velocity and pressure) and sensitivity. This is followed by concluding remarks together with future perspectives.

Is race important in genomic classification of hematological neoplasms?

In recent years, genome-based classifications for hematological neoplasms have been proposed successively and proved to be more accurate than histologic classifications. However, some previous studies have reported the racial differences of genetic landscape in persons with hematological neoplasms including myelodysplastic syndromes (MDS), which may cause a genomic classification based on a particular ethnic group does not operate in other races. To determine whether race plays an important role in the genomic-based classification, we validated a newly proposed genomic classification of MDS (J Clin Oncol.2021; JCO2001659), which was based on a large European database, in Chinese patients from our center. Our results showed significant differences between Chinese and European patients including proportion of each group to overall cohort when applying this novel genomic classification. Our data indicate that a genomic classification of hematological neoplasms probably should be revised according to specific genetic features in different races.

Chemical reactions of a CL-20 crystal under heat and shock determined by ReaxFF reactive molecular dynamics simulations.

Studying the chemical reactions of hexanitrohexaazaisowurtzitane (CL-20) under heat and shock is helpful to understand its sensitivity and shock initiation mechanism. In this work, several molecular dynamics simulations were performed under three different conditions: high temperature, high temperature and pressure, and shock. The formation and breakage of chemical bonds, changes of bond lengths, and initial reactions were analysed. It was found that the main small-molecule product of CL-20 during initial decomposition under the three different conditions was always NO2, but the generation pathways were different. At high temperatures, NO2 was generated by the direct cleavage of N-NO2 bonds. In contrast, high pressure and shock promoted the transfer of O atoms to N atoms connected to NO2, leading to the breakage of N-NO2 bonds. Almost all NO2 originated from the transfer of O atoms under the shock conditions.

A quantum-based molecular dynamics study of the ICM-102/HNO3 host-guest reaction at high temperatures.

The contradiction between energy and safety of explosives is better balanced by the host-guest inclusion strategy. Understanding the reaction mechanism of the host-guest explosive is necessary. To deeply analyze the role of the small guest molecules in the host-guest system, a quantum-based molecular dynamics method was used to calculate the initial decomposition reaction of the new host-guest explosive ICM-102/HNO3 against the pure ICM-102 at several high temperatures. The incorporation of HNO3 had no significant influence on the initial decomposition step of ICM-102. Conversely, the earliest intramolecular hydrogen transfer reaction is delayed partly because the H and O atoms of HNO3 connect with the O and H atoms of ICM-102, respectively. As the reaction proceeds, guest molecules get heavily involved in the reaction and increase the reaction rate. The generation rate and quantity of the small oxidizing molecules in the final product were increased significantly in the ICM-102/HNO3 system. These mechanisms revealed that HNO3 molecules inhibit the early stages of the initial decomposition of ICM-102 to some extent, and play an important role in accelerating the decomposition subsequently.

Thermal stability mechanism via energy absorption by chemical bonds bending and stretching in free space and the interlayer reaction of layered molecular structure explosives.

Layered molecular structure explosives have the characteristic of great thermal stability. Understanding the mechanism of thermal stability and the reactions of layered molecular structure explosives can provide new ideas for the design of thermally stable explosives. In a molecular dynamics simulation of thermal decomposition of the layered molecular structure explosive 2,4,6-triamino-5-nitropyrimidine-1,3-dioxide, we find that the layered molecular structure provides free space for chemical bond deflection and expansion so that the external energy absorbed by chemical bonds on nonbenzene rings can be converted into angle bending energy and bond-stretching energy, which makes chemical bonds difficult to break and increases the thermal stability of the explosives. In the layered molecular structure explosive reactions, hydrogen-oxygen-bonded interlayer dimerizations and hydrogen interlayer transfer reactions are dominant.

Treatment of Temporomandibular Joint Disorders by Ultrashort Wave and Extracorporeal Shock Wave: A Comparative Study.

BACKGROUND This study was carried out to compare the therapeutic efficacy of extracorporeal shock wave (ESW) and ultrashort wave (UW) for temporomandibular joint disorder (TMD). MATERIAL AND METHODS A total of 80 patients with myofascial pain and TMD were enrolled in this study. The subjects were randomized to receive ESW or UW treatments. Patients in the ESW group received 1 ESW treatment for 4 weeks and patients in the US group were given US treatment once a day for 5 days per week for 4 weeks. The pain was measured using visual analog scale (VAS) and mouth opening was determined as pain-free maximum mouth opening (MMO) before and 4 weeks after the treatments. Other parameters assessed included functional indexes of temporomandibular joint such as mandibular movement (MM), joint noise (JN), joint press (JP), and disability index (DI). RESULTS After therapy, VAS, MMO, MM, JN, JP, and DI in ESW group, and VAS in UW group were significantly improved (P<0.05) as compared to before therapy. VAS, MMO, and the functional indexes of temporomandibular joint in the ESW group were significantly better than those in the UW group (1.79 vs. 2.00, 3.23 vs. 2.03, 1.79 vs. 2.41, 1.45 vs. 2.27, 1.55 vs. 2.59, and 3.30 vs. 4.79, respectively. P<0.05). CONCLUSIONS ESW significantly reduces pain and improves the functional indexes of temporomandibular joint and mouth opening limit for TMD patients as compared with UW therapy.

Effect of density on the thermal decomposition mechanism of ε-CL-20: a ReaxFF reactive molecular dynamics simulation study.

The explosive detonation reaction occurs when explosives are compressed by different shock strengths, and the degree of compression affects the chemical reaction of the detonation process. The thermal decomposition mechanism of explosives under different compression densities has thus attracted significant research interest, and a better understanding of this mechanism would be helpful for determining the mechanism of the detonation reaction of explosives. In this study, a ε-CL-20 supercell was constructed, and the thermal decomposition was calculated at different compression densities and temperatures using molecular dynamics simulations based on the ReaxFF-lg reactive force field. We analyzed the effect of density on the main elementary reaction, which consists of the initial reaction and the formation of final products. In addition, we studied the effect of density on the generation of clusters and the reaction kinetics of the thermal decomposition. The results indicate that the initial reaction pathway of the CL-20 molecule is the cleavage of the N-NO2 bond at different densities and that the frequency of N-NO2 bond breakage decreases at high density. As the density increases, clusters easily form and are resistant to decomposition at the later stage of thermal decomposition, which eventually leads to a decrease in the number of final products. Increasing the initial density of CL-20 significantly increases the reaction rate of the initial decomposition but hardly changes the activation energy of the decomposition.