An optimization approach to establish dynamical equivalence for soft and rigid impact models.

This paper studies a computational approach aimed at establishing equivalent dynamical responses within oscillatory impacting systems subject to soft and rigid constraints. The proposed method incorporates an adaptive differential evolution algorithm with the Metropolis criterion to determine the stiffness and damping parameters of the soft constraint for a prescribed coefficient of restitution governing the rigid constraint. The proposed algorithm aims to establish an equivalent dynamical response of the two models based on constraints regarding energy dissipation and contact time duration. Upon examining the dynamical responses of the two impact cases, they exhibit nearly identical outcomes in the two-parameter bifurcation diagrams when subjected to a large restitution coefficient. However, discrepancies arise between the results of the two models when the restitution coefficient is low. Detailed numerical tests, conducted using the proposed method, demonstrate enhanced effectiveness compared to previous techniques, such as the prediction formulas for the different related soft impact model outlined by Okolewski and Blazejczyk-Okolewska [Chaos 31(8), 083110 (2021)]. This method not only finds application in experimentally identifying the physical properties of an impact surface but also provides convenience in employing soft models within impacting systems, which could then avoid potential inaccuracies in handling discontinuities by some integrator during velocity jumps before and after impacts.

XAF1 promotes osteoclast apoptosis by antagonizing the XIAP-caspase axis.

Background: Over-activated osteoclast (OC) is a major cause of diseases related to bone loss and bone metabolism. Both bone resorption inhibition and apoptosis induction of osteoclast are crucial in treating these diseases. X-linked inhibitor of apoptosis protein (XIAP)-associated factor 1 (XAF1) is an important interferon-stimulated and apoptotic gene. However, how XAF1 regulates bone formation and remodeling is unknown. Methods: We generate global and chimeric Xaf1 knockout mouse models and utilize these models to explore the function and mechanism of XAF1 in regulating bone formation and remodeling in vivo and in vitro. Results: We show that XAF1 depletion enhances osteoclast generation in vitro. XAF1 knockout increases osteoclast number and bone resorption, thereby exacerbating bone loss in both OVX and osteolysis models. Activation of XAF1 with BV6 (a potent XIAP inhibitor) suppresses osteoclast formation. Mechanistically, XAF1 deletion decreases osteoclast apoptosis by facilitating the interaction between XIAP and caspase-3/7. Conclusions: Our data illustrates an essential role of XAF1 in controlling osteoclastogenesis in both osteoporosis and osteolysis mouse models and highlights its underlying mechanism, indicating a potential role in clinical treatment.The translational potential of this article: The translation potential of this article is that we first indicated that osteoclast apoptosis induced by XAF1 contribute to the progression of osteoporosis and osteolysis, which provides a novel strategy in the prevention of osteoporosis and osteolysis.

Dietary probiotic based on a dual-strain B. subtilis improves immunity, intestinal health and growth performance of broiler chickens.

The study investigated the effects of dietary probiotic of dual-strain Bacillus subtilis (BS) on production performance, intestinal barrier parameters, and microbiota in broiler chickens. In a randomized trial, male broiler chickens were allocated into three groups, a control group (basal diet), BS300 group (basal diet with 300 mg/kg BS), and BS500 group (basal diet with 500 mg/kg BS). The inclusion of 500 mg/kg BS significantly reduced the feed conversion ratio by 4.55% during the starting phase. Both 300 and 500 mg/kg BS supplementation increased jejunal villus height (by 17.89% and 24.8%, respectively) significantly and decreased jejunal crypt depth (by 27.2% and 31.9%, respectively) on day 21. The addition of 500 mg/kg BS significantly elevated the gene expression of occludin on day 35. Moreover, BS supplementation enhanced cytokine levels and immunoglobulins in both serum and jejunal mucosa. Microbial analysis indicated that BS increased the abundance of potential probiotics (Sutterella) and butyrate-producing bacteria (Lachnoclostridium, Tyzzerella, Anaerostipes, Clostridium_sensu_stricto_13, Prevotellaceae_NK3B31_group, and Lachnospiraceae_UCG-010). The abundances of Anaerostipes and Sutterella, are significantly correlated with growth performance and immune function. In conclusion, dietary supplementation with BS improved the growth performance, potentially through the regulation of immunity, intestinal barrier function, and microbiota in broilers. Notably, 500 mg/kg of BS exhibited more benefits for broilers compared to the 300 mg/kg.

Ketamine ameliorates post-traumatic social avoidance by erasing the traumatic memory encoded in VTA-innervated BLA engram cells.

Erasing traumatic memory during memory reconsolidation is a promising retrieval-extinction strategy for post-traumatic stress disorder (PTSD). Here, we developed an acute social defeat stress (SDS) mouse model with short-term and re-exposure-evoked long-term social avoidance. SDS-associated traumatic memories were identified to be stored in basolateral amygdala (BLA) engram cells. A single intraperitoneal administration of subanesthetic-dose ketamine within, but not beyond, the re-exposure time window significantly alleviates SDS-induced social avoidance, which reduces the activity and quantity of reactivated BLA engram cells. Furthermore, activation or inhibition of dopaminergic projections from the ventral tegmental area to the BLA effectively mimics or blocks the therapeutic effect of re-exposure with ketamine and is dopamine D2 receptor dependent. Single-cell RNA sequencing reveals that re-exposure with ketamine triggered significant changes in memory-related pathways in the BLA. Together, our research advances the understanding of how ketamine mitigates PTSD symptoms and offers promising avenues for developing more effective treatments for trauma-related disorders.

Chromosome-level genome assembly of the two-spotted spider mite Tetranychus urticae.

The two-spotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae), is a notorious pest in agriculture that has developed resistance to almost all chemical types used for its control. Here, we assembled a chromosome-level genome for the TSSM using Illumina, Nanopore, and Hi-C sequencing technologies. The assembled contigs had a total length of 103.94 Mb with an N50 of 3.46 Mb, with 87.7 Mb of 34 contigs anchored to three chromosomes. The chromosome-level genome assembly had a BUSCO completeness of 94.8%. We identified 15,604 protein-coding genes, with 11,435 genes that could be functionally annotated. The high-quality genome provides invaluable resources for the genetic and evolutionary study of TSSM.

Development of Negative-Temperature Cement Emulsified Asphalt Spraying Materials Based on Spraying Performance and Rheological Parameters.

To develop a cement emulsified asphalt composite (CEAC) that can be sprayed under a plateau negative temperature environment, the effects of the water-solid ratio, calcium aluminate cement substitution rate, emulsified asphalt content, sand-binder ratio, and polyvinyl alcohol (PVA) fiber content on the spraying performance and rheological parameters of CEAC were explored through the controlled variable method. Additionally, the correlation between the spraying performance and rheological parameters of CEAC was established, and the optimal proportion of CEAC was determined. Then, the difference in frost resistance and pore structure between the cement slurry (CS) without emulsified asphalt and CEAC at the optimum proportion was analyzed. The results showed that the optimum proportions for sprayed CEAC were 0.14 water-solid ratio, 0.5 sand-binder ratio, 25% substitution of calcium aluminate cement, 5% emulsified asphalt content, and 1.5% PVA fiber volume mixing. The yield stress and plastic viscosity of CEAC were positively correlated with the build-up thickness, whereas the rebound rate and the latter showed a negative correlation. The spraying performance may be described by the rheological parameters; the ranges of yield stress and plastic viscosity of 2.37-3.95 Pa·s and 77.42-108.58 Pa, respectively, produced the best spray ability. After undergoing an equivalent number of freeze-thaw cycles, CEAC exhibited lower mass and strength loss rates compared to CS, thereby demonstrating superior frost resistance. In addition, the pore structure analysis showed that the difference in capillary and macropore contents was the main reason for the variability in frost resistance between CS and CEAC.

Identification of the serum metabolites associated with cow milk consumption in Chinese Peri-/Postmenopausal women.

Cow milk consumption (CMC) and downstream alterations of serum metabolites are commonly considered important factors regulating human health status. Foods may lead to metabolic changes directly or indirectly through remodelling gut microbiota (GM). We sought to identify the metabolic alterations in Chinese Peri-/Postmenopausal women with habitual CMC and explore if the GM mediates the CMC-metabolite associations. 346 Chinese Peri-/Postmenopausal women participants were recruited in this study. Fixed effects regression and partial least squares discriminant analysis (PLS-DA) were applied to reveal alterations of serum metabolic features in different CMC groups. Spearman correlation coefficient was computed to detect metabolome-metagenome association. 36 CMC-associated metabolites including palmitic acid (FA(16:0)), 7alpha-hydroxy-4-cholesterin-3-one (7alphaC4), citrulline were identified by both fixed effects regression (FDR < 0.05) and PLS-DA (VIP score > 2). Some significant metabolite-GM associations were observed, including FA(16:0) with gut species Bacteroides ovatus, Bacteroides sp.D2. These findings would further prompt our understanding of the effect of cow milk on human health.

Alternating bilateral sensory stimulation alleviates alcohol-induced conditioned place preference via a superior colliculus-VTA circuit.

Alcohol is the most widely used addictive substance, potentially leading to brain damage and genetic abnormalities. Despite its prevalence and associated risks, current treatments have yet to identify effective methods for reducing cravings and preventing relapse. In this study, we find that 4-Hz alternating bilateral sensory stimulation (ABS) effectively reduces ethanol-induced conditioned place preference (CPP) in male mice, while 4-Hz flash light does not exhibit therapeutic effects. Whole-brain c-Fos mapping demonstrates that 4-Hz ABS triggers notable activation in superior colliculus GABAergic neurons (SCGABA). SCGABA forms monosynaptic connections with ventral tegmental area dopaminergic neurons (VTADA), which is implicated in ethanol-induced CPP. Bidirectional chemogenetic manipulation of SC-VTA circuit either replicates or blocks the therapeutic effects of 4-Hz ABS on ethanol-induced CPP. These findings elucidate the role of SC-VTA circuit for alleviating ethanol-related CPP by 4-Hz ABS and point to a non-drug and non-invasive approach that might have potential for treating alcohol use disorder.

On the quality of commercial chemical vapour deposited hexagonal boron nitride.

The semiconductors industry has put its eyes on two-dimensional (2D) materials produced by chemical vapour deposition (CVD) because they can be grown at the wafer level with small thickness fluctuations, which is necessary to build electronic devices and circuits. However, CVD-grown 2D materials can contain significant amounts of lattice distortions, which degrades the performance at the device level and increases device-to-device variability. Here we statistically analyse the quality of commercially available CVD-grown hexagonal boron nitride (h-BN) from the most popular suppliers. h-BN is of strategic importance because it is one of the few insulating 2D materials, and can be used as anti-scattering substrate and gate dielectric. We find that the leakage current and electrical homogeneity of all commercially available CVD h-BN samples are significantly worse than those of mechanically exfoliated h-BN of similar thickness. Moreover, in most cases the properties of the CVD h-BN samples analysed don't match the technical specifications given by the suppliers, and the sample-to-sample variability is unsuitable for the reproducible fabrication of capacitors, transistors or memristors in different batches. In the short term, suppliers should try to provide accurate sample specifications matching the properties of the commercialized materials, and researchers should keep such inaccuracies in mind; and in the middle term suppliers should try to reduce the density of defects to enable the fabrication of high-performance devices with high reliability and reproducibility.

Epoxy Resins With Controllable "Thermally Conductive-Self-Healing" Synergies: a New Material to Meet the Needs of Flexible Electronic Devices.

With the popularization of 5G technology and artificial intelligence, thermally conductive epoxies with self-healing ability will be widely used in flexible electronic materials. Although many compounds containing both performances have been synthesized, there is little systematic theory to explain the coordination mechanism. In this paper, alkyl chains of different lengths were introduced to epoxies to discuss the thermally conductive, the self-healing performance, and the synergistic effect. A series of electronic-grade biphenyl epoxies (4,4'-bis(oxiran-2-ylmethoxy)-1,1'-biphenyl (1), 4,4'-bis(2-(oxiran-2-yl)ethoxy)-1,1'-biphenyl (2), 4,4'-bis(3-(oxiran-2-yl)propoxy)-1,1'-biphenyl (3), and 4,4'-bis(4-(oxiran-2-yl)butoxy)-1,1'-biphenyl (4) were synthesized and characterized. Furthermore, they were cured with decanedioic acid to produce polymers. Results showed that alkyl chains can both affect the two properties, and the epoxies suitable for specific application scenarios can be prepared by adjusting the length of alkyl chains. In terms of thermal conductivity, compound 1 was a most promising material. However, compound 4 was expected to be utilized in flexible electronic devices because of its acceptable thermal conductivity, self-healing ability, transparency, and flexibility.

CRYAB suppresses ferroptosis and promotes osteogenic differentiation of human bone marrow stem cells via binding and stabilizing FTH1.

BACKGROUND: Bone formation and homeostasis are greatly dependent on the osteogenic differentiation of human bone marrow stem cells (BMSCs). Therefore, revealing the mechanisms underlying osteogenic differentiation of BMSCs will provide new candidate therapeutic targets for osteoporosis. METHODS: The osteogenic differentiation of BMSCs was measured by analyzing ALP activity and expression levels of osteogenic markers. Cellular Fe and ROS levels and cell viability were applied to evaluate the ferroptosis of BMSCs. qRT-PCR, Western blotting, and co-immunoprecipitation assays were harnessed to study the molecular mechanism. RESULTS: The mRNA level of CRYAB was decreased in the plasma of osteoporosis patients. Overexpression of CRYAB increased the expression of osteogenic markers including OCN, OPN, RUNX2, and COLI, and also augmented the ALP activity in BMSCs, on the contrary, knockdown of CRYAB had opposite effects. IP-MS technology identified CRYAB-interacted proteins and further found that CRYAB interacted with ferritin heavy chain 1 (FTH1) and maintained the stability of FTH1 via the proteasome mechanism. Mechanically, we unraveled that CRYAB regulated FTH1 protein stability in a lactylation-dependent manner. Knockdown of FTH1 suppressed the osteogenic differentiation of BMSCs, and increased the cellular Fe and ROS levels, and eventually promoted ferroptosis. Rescue experiments revealed that CRYAB suppressed ferroptosis and promoted osteogenic differentiation of BMSCs via regulating FTH1. The mRNA level of FTH1 was decreased in the plasma of osteoporosis patients. CONCLUSIONS: Downregulation of CRYAB boosted FTH1 degradation and increased cellular Fe and ROS levels, and finally improved the ferroptosis and lessened the osteogenic differentiation of BMSCs.

Circ_0072088 promotes breast carcinoma progression via modulating miR-607/RNF2 axis.

OBJECTIVES: To explore how the circular non-coding RNA circ_0072088 influences the progression of breast carcinoma (BC) by affecting cell behavior. METHODS: We measured the levels of circ_0072088, microRNA-607 (miR-607), and ring finger protein 2 (RNF2) mRNA levels in BC tissues and cell lines using quantitative real-time PCR. We also conducted cell counting kit-8 (CCK-8), BrdU incorporation, and flow cytometry assays to assess cell viability, cell cycle, and apoptosis, respectively. RESULTS: We observed increased levels of circ_0072088 and RNF2, and decreased levels of miR-607 in BC tissues. Overexpressing circ_0072088 promoted BC cell proliferation and cell cycle progression while inhibiting apoptosis. Conversely, silencing circ_0072088 had the opposite effects. Our data suggest that circ_0072088 directly targets and downregulates miR-607, which in turn upregulates RNF2, a target of miR-607. Moreover, miR-607 overexpression could mitigate the pro-proliferative and anti-apoptotic effects of circ_0072088 on BC cells. CONCLUSION: Circ_0072088 drives BC progression by downregulating miR-607 and upregulating RNF2, thereby promoting cell proliferation and cycle progression while reducing apoptosis.

Electronic Patient-Reported Outcome-Based Symptom Management Versus Usual Care After Lung Cancer Surgery: Long-Term Results of a Multicenter, Randomized, Controlled Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We previously reported superior symptom control of electronic patient-reported outcome (ePRO)-based symptom management after lung cancer surgery for up to 1 month postdischarge. Here, we present the long-term results (1-12 months) of this multicenter, randomized trial, where patients were assigned 1:1 to receive postoperative ePRO-based symptom management or usual care daily postsurgery, twice weekly postdischarge until 1 month, and at 3, 6, 9, and 12 months postdischarge. Long-term patient-reported outcomes were assessed with MD Anderson Symptom Inventory-Lung Cancer module. Per-protocol analyses were performed with 55 patients in the ePRO group and 57 in the usual care group. At 12 months postdischarge, the ePRO group reported significantly fewer symptom threshold events (any of the five target symptom scored ≥4; median [IQR], 0 [0-0] v 0 [0-1]; P = .040) than the usual care group. From 1 to 12 months postdischarge, the ePRO group consistently reported significantly lower composite scores for physical interference (estimate, -0.86 [95% CI, -1.32 to -0.39]) and affective interference (estimate, -0.70 [95% CI, -1.14 to -0.26]). Early intensive ePRO-based symptom management after lung cancer surgery reduced symptom burden and improved functional status for up to 1 year postdischarge, supporting its integration into standard care.

Influence of different magnetic forces on the effect of colonic anastomosis in rats.

BACKGROUND: Despite much work having been conducted on magnetic compression anastomosis (MCA) in the digestive tract, there are no reports on the influence of magnetic force on the anastomosis. AIM: To investigate the effect of different magnetic force magnets on the MCA of the digestive tract. METHODS: Two groups of magnets of the same sizes but different magnetic forces were designed and produced. A total of 24 Sprague-Dawley rats were randomly assigned into two groups (powerful magnet group and common magnet group), with 12 rats in each group. Two types of magnets were used to complete the colonic side-to-side anastomosis of the rats. The operation time and magnet discharge time were recorded. The anastomotic specimens were obtained 4 wk after the operation and then the burst pressure and diameter of the anastomosis were measured, and the anastomosis was observed via the naked eye and subjected to histological examination. RESULTS: The magnetic forces of the powerful and common magnet groups at zero distance were 8.26 N and 4.10 N, respectively. The colonic side-to-side anastomosis was completed in all 24 rats, and the operation success rate and postoperative survival rate were 100%. No significant difference was noted in the operation time between the two groups. The magnet discharge time of the powerful magnet group was slightly longer than that of the common magnet group, but the difference was not statistically significant (P = 0.513). Furthermore, there was no statistical difference in the burst pressure (P = 0.266) or diameter of magnetic anastomosis (P = 0.095) between the two groups. The gross specimens of the two groups showed good anastomotic healing, and histological observation indicated good mucosal continuity without differences on healing. CONCLUSION: In the rat colonic side-to-side MCA model, both the powerful magnet with 8.26 N and the common magnet with 4.10 N showed no significant impact on the anastomosis establishment process or its effect.

Correlation between 146S Antigen Content in Foot-and-Mouth Disease Inactivated Vaccines and Immunogenicity Level and Vaccine Potency Alternative Test Methods.

To investigate the association between 146S antigen contents in FMD inactivated vaccines and levels of antiviral immunity, this study vaccinated 30 kg pigs with three batches of FMD types O and A bivalent inactivated vaccines. Antibody titers and interferon-gamma (IFN-γ) secretion levels were measured on days 7, 14, 21, and 28 after primary immunization and on days 14 and 28 following booster immunization to assess associations between 146S contents and both antibody titers and IFN-γ secretion levels. Furthermore, 30 kg pigs were vaccinated with 46 batches of FMD type O inactivated vaccines and challenged on day 28, after which PD50 values were determined to evaluate the association between 146S content and PD50. The findings suggested that antibody titers and IFN-γ secretion levels at specific time points after immunization were positively associated with 146S contents. Additionally, 146S content showed a positive correlation with PD50, with greater PD50 values recorded for 146S contents ranging from 4.72 to 16.55 µg/dose. This investigation established a significant association between the 146S content in FMD inactivated vaccines and induced immune response against FMDV, thereby emphasizing its critical role in vaccine quality control. The determination of 146S content could serve as a new method for potency testing, offering an alternative to animal challenge tests.

Tumor-associated antigen-specific cell imaging based on upconversion luminescence and nucleic acid rolling circle amplification.

Tumor-associated antigen (TAA)-based diagnosis has gained prominence for early tumor screening, treatment monitoring, prognostic assessment, and minimal residual disease detection. However, limitations such as low sensitivity and difficulty in extracting non-specific binding membrane proteins still exist in traditional detection methods. Upconversion luminescence (UCL) exhibits unique physical and chemical properties under wavelength near-infrared light excitation. Rolling circle amplification (RCA) is an efficient DNA amplification technique with amplification factors as high as 105. Therefore, the above two excellent techniques can be employed for highly accurate imaging analysis of tumor cells. Herein, we developed a novel nanoplatform for TAA-specific cell imaging based on UCL and RCA technology. An aptamer-primer complex selectively binds to Mucin 1 (MUC1), one of TAA on cell surface, to trigger RCA reaction, generating a large number of repetitive sequences. These sequences provide lots of binding sites for complementary signal probes, producing UCL from lanthanide-doped upconversion nanoparticles (UCNPs) after releasing quencher group. The experimental results demonstrate the specific attachment of upconversion nanomaterials to cancer cells which express a high level of MUC1, indicating the potential of UCNPs and RCA in tumor imaging.

Vitamin C regulates skeletal muscle post-injury regeneration by promoting myoblast proliferation through its direct interaction with the Pax7 protein.

Previous studies have shown that vitamin C (VC), an essential vitamin for the human body, can promote the differentiation of muscle satellite cells (MuSCs) in vitro and play an important role in skeletal muscle post-injury regeneration. However, the molecular mechanism of VC regulating MuSC proliferation has not been elucidated. In this study, the role of VC in promoting MuSC proliferation and its molecular mechanism were explored using cell molecular biology and animal experiments. The results showed that VC accelerates the progress of skeletal muscle post-injury regeneration by promoting MuSC proliferation in vivo. VC can also promote skeletal muscle regeneration in the case of atrophy. Using the C2C12 myoblast murine cell line, we observed that VC also stimulated cell proliferation. In addition, after an in vitro study establishing the occurrence of a physical interaction between VC and Pax7, we observed that VC also upregulated the total and nuclear Pax7 protein levels. This mechanism increased the expression of Myf5 (Myogenic Factor 5), a Pax7 target gene. This study establishes a theoretical foundation for understanding the regulatory mechanisms underlying VC-mediated MuSC proliferation and skeletal muscle regeneration. Moreover, it develops the application of VC in animal muscle nutritional supplements and treatment of skeletal muscle-related diseases.

Risk model based on genes regulating the response of tumor cells to T-cell-mediated killing in esophageal squamous cell carcinoma.

Immune checkpoint inhibitors (ICIs) represent a promising therapeutic approach for esophageal squamous cell carcinoma (ESCC). However, the subpopulations of ESCC patients expected to benefit from ICIs have not been clearly defined. The anti-tumor cytotoxic activity of T cells is an important pharmacological mechanism of ICIs. In this study, the prognostic value of the genes regulating tumor cells to T cell-mediated killing (referred to as GRTTKs) in ESCC was explored by using a comprehensive bioinformatics approach. Training and validation datasets were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. A prognostic risk scoring model was developed by integrating prognostic GRTTKs from TCGA and GEO datasets using a ridge regression algorithm. Patients with ESCC were divided into high- and low-risk groups based on eight GRTTKs (EIF4H, CDK2, TCEA1, SPTLC2, TMEM209, RGP1, EIF3D, and CAPZA3) to predict overall survival in the TCGA cohort. Using Kaplan-Meier curves, receiver operating characteristic curves, and C-index analysis, the high reliability of the prognostic risk-scoring model was certified. The model scores served as independent prognostic factors, and combining clinical staging with risk scoring improved the predictive value. Patients in the high-risk group exhibited abundant immune cell infiltration, including immune checkpoint expression, antigen presentation capability, immune cycle gene expression, and high tumor inflammation signature scores. The high-risk group exhibited a greater response to immunotherapy and neoadjuvant chemotherapy than the low-risk group. Drug sensitivity analysis demonstrated lower IC50 for AZD6244 and PD.0332991 in high-risk groups and lower IC50 for cisplatin, ATRA, QS11, and vinorelbine in the low-risk group. Furthermore, the differential expression of GRTTK-related signatures including CDK2, TCEA1, and TMEM209 were verified in ESCC tissues and paracancerous tissues. Overall, the novel GRTTK-based prognostic model can serve as indicators to predict the survival status and immunotherapy response of patients with ESCC, thereby providing guidance for the development of personalized treatment strategies.

[Short-term Effect of Venetoclax Combined with Azacitidine and "7+3" Regimen in the Treatment of Newly Diagnosed Elder Patients with Acute Myeloid Leukemia].

OBJECTIVE: To compare the short-term effect and adverse reaction of venetoclax (VEN) combined with azacitidine (AZA) versus "7+3" regimen in newly diagnosed elder patients with acute myeloid leukemia (AML). METHODS: From January 2021 to January 2022, the clinical data of seventy-nine newly diagnosed elder patients with AML at the Second Hospital of Shanxi Medical University and the Shanxi Bethune Hospital were retrospectively analyzed, including VEN+AZA group (41 cases) and "7+3" group (38 cases). The propensity score matching(PSM) method was used to balance confounding factors， then response， overall survival(OS), progressionfree survival(PFS) and adverse reactions between the two groups were compared. RESULTS: The ORR of VEN+AZA group and "7+3" group was 68% and 84%, respectively, and the CRc was 64% and 72%, respectively, the differents were not statistically significant (P >0.05). In the VEN+AZA group, there were 5 non-remission (NR) patients, 4 with chromosome 7 abnormality (7q-/-7), and 1 with ETV6 gene mutation. Median followed-up time between the two groups was 8 months and 12 months, respectively, and the 6-months OS was 84% vs 92% (P =0.389), while 6-months PFS was 84% vs 92% (P =0.258). The main hematological adverse reactions in two groups were stage Ⅲ-Ⅳ myelosuppression, and the incidence rate was not statistically different(P >0.05). The median time of neutrophil recovery in two groups was 27(11-70) d, 25(14-61) d （P =0.161）, and platelet recovery was 27(11-75) d, 25(16-50) d （P =0.270）, respectively. The infection rate of VEN+AZA group was lower than that of "7+3" group (56% vs 88%, P =0.012）. The rate of lung infections of two groups was 36% and 64%, respectively, the difference was statistically significant (P =0.048). CONCLUSION: The short-term effect of VEN+AZA group and "7+3" regimens in eldrly AML patients are similar， but the VEN+AZA regimen had a lower incidence of infection. The presence of chromosome 7 abnormality（7q-/-7） may be a poor prognostic factor for elderly AML patients treated with VEN+AZA.