Bo Lu’s research while affiliated with Shenzhen University and other places

Background and Purpose The ability of autologous hematopoietic stem cell transplantation (ASCT) to improve the benefit of patients with high-risk diffuse large B-cell lymphoma (DLBCL) who achieved complete remission (CR) following induction chemotherapy is controversial. This multicenter real-world study aimed to explore the efficacy and safety of the rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen followed by consolidated ASCT therapy in newly diagnosed DLBCL. Methods From June 2018 to June 2021, the clinical data of patients with high-risk DLBCL who reached CR after receiving the R-CHOP regimen from ten lymphoma diagnosis and treatment centers were analyzed. Patients were included in the R-CHOP+ASCT (with consolidated ASCT therapy, n = 60) and R-CHOP (follow-up without consolidated ASCT therapy, n = 60) groups. The efficacy in the two groups was compared by difference analysis, and the safety of R-CHOP+ASCT was analyzed. Results Until June 2024, the median follow-up times for the R-CHOP+ASCT and R-CHOP groups were 44 (37.25–56) and 43.5 (38–52) months, respectively. Survivors were followed up for at least 36 months. In the R-CHOP+ASCT group, the 3-year disease-free survival (DFS) and overall survival (OS) rates were 89.7% and 96.7% and those in the R-CHOP group were 63.9% and 85.9%, respectively. The 3-year DFS rate in the R-CHOP+ASCT group was significantly higher than that in the R-CHOP group (89.7% vs 63.9%, P = 0.001); no significant difference was found in the 3-year OS rate between the R-CHOP+ASCT and R-CHOP groups (96.7% vs 85.9%, P = 0.113). The 5-year DFS and OS rates in the R-CHOP+ASCT group were 73.6% and 77.6% and those in the R-CHOP group were 56.5% and 81.1%, respectively. The 5-year DFS rate in the R-CHOP+ASCT group was significantly higher than that in the R-CHOP group (73.6% vs 56.5%, P = 0.009), whereas no significant difference was found in the 5-year OS rate between the R-CHOP+ASCT and R-CHOP groups (77.6% vs 81.1%, P = 0.246). In the Cox multifactorial analysis, discontinuous consolidated ASCT therapy, bone marrow invasion, and dual expression were poor prognostic factors that affect DFS [hazard ratio (HR), 5.710; 95% confidence interval (CI), 2.241–14.548, P < 0.001; HR, 4.324; 95% CI, 1.890–9.893, P = 0.001; HR, 2.565; 95% CI, 1.145–5.747, P = 0.022, respectively] and dual expression was a poor prognostic factor for OS (HR, 3.486; 95% CI, 1.300–9.344, P = 0.013). Grade IV myelosuppression after transplantation developed in the R-CHOP+ASCT group, and other common grade 3 or 4 treatment-related adverse events were infection and fever. Conclusion For patients with newly diagnosed high-risk DLBCL, consolidated ASCT therapy can increase the DFS rate of those with CR status following the R-CHOP regimen, and the safety is controllable.

Cold-atom magnetometers can achieve an exceptional combination of superior sensitivity and high spatial resolution. One key challenge these quantum sensors face is improving the sensitivity within a given timeframe while preserving a high dynamic range. Here, we experimentally demonstrate an adaptive entanglement-free cold-atom magnetometry with both superior sensitivity and high dynamic range. Employing a tailored adaptive Bayesian quantum estimation algorithm designed for Ramsey interferometry using coherent population trapping (CPT), cold-atom magnetometry facilitates adaptive high-precision detection of a direct-current (d.c.) magnetic field with high dynamic range. Through implementing a sequence of correlated CPT-Ramsey interferometry, the sensitivity significantly surpasses the standard quantum limit with respect to total interrogation time. We yield a sensitivity of 6.8$\pm$0.1 picotesla per square root of hertz over a range of 145.6 nanotesla, exceeding the conventional frequentist protocol by 3.3$\pm$0.1 decibels. Our study opens avenues for the next generation of adaptive cold-atom quantum sensors, wherein real-time measurement history is leveraged to improve their performance.

Cold-atom magnetometers can achieve an exceptional combination of superior sensitivity and high spatial resolution. One key challenge that these quantum sensors face is improving the sensitivity within a given timeframe while preserving a high dynamic range. Here, we experimentally demonstrate an adaptive entanglement-free cold-atom magnetometry with both superior sensitivity and high dynamic range. Using a tailored adaptive Bayesian quantum estimation algorithm designed for Ramsey interferometry using coherent population trapping (CPT), cold-atom magnetometry facilitates adaptive high-precision detection of a dc magnetic field with high dynamic range. Through implementing a sequence of correlated CPT-Ramsey interferometry, the sensitivity significantly surpasses the standard quantum limit with respect to total interrogation time. We yield a sensitivity of 6.8 ± 0.1 picotesla per square root of hertz over a range of 145.6 nanotesla, exceeding the conventional frequentist protocol by 3.3 ± 0.1 decibels. Our study opens avenues for the next generation of adaptive cold-atom quantum sensors, wherein real-time measurement history is leveraged to improve their performance.

The noise in absorption imaging of cold atoms significantly impacts measurement accuracy across a range of applications with ultracold atoms. It is crucial to adopt an approach that offers effective denoising capabilities without compromising the unique structure of atom clouds. Here, we introduce, to our knowledge, a novel image enhancement algorithm for cold atomic absorption imaging. The algorithm successfully suppresses background noise, enhancing image contrast significantly. Experimental results showcase that this approach can improve the image’s signal-to-noise ratio by about 10 dB and enhance the uncertainty of cold atom number measurements by approximately tenfold, preserving the spatial distribution of the atom clouds. Moreover, the method exhibits exceptional performance and robustness when confronted with fringe noise and multi-component imaging scenarios, offering high stability. Importantly, this method can perform denoising based on a single image (without the need to establish a reference library), and the optimization process is entirely automated, eliminating the need for manual parameter selection. The method is both compatible and practical, making it applicable to various cold atom absorption imaging fields.

Tripartite motif-containing protein 31 (Trim31) is known to be involved in various pathological conditions, including heart diseases. Nonetheless, its specific involvement in heart failure (HF) has yet to be determined. In this study, we examined the function and mechanism of Trim31 in HF by using mice with cardiac-specific knockout (cKO) of Trim31. The HF mouse model was induced via the subcutaneous injection of isoproterenol (ISO). We observed a decrease in Trim31 expression in the heart tissues of mice with HF. Compared with wild-type (WT) mice, Trim31 cKO mice presented more severe characteristics of HF, including worsened cardiac dysfunction, hypertrophy, and fibrosis. However, these symptoms in Trim31 cKO mice were significantly reversed when they received an intramyocardial injection of recombinant adeno-associated virus (AAV) expressing Trim31. Excessive activation of the NLRP3 inflammasome, manifested by increased levels of NLRP3, ASC, cleaved Caspase-1, cleaved GSDMD, IL-1β, and IL-18, was observed in Trim31 cKO mice with HF. However, Trim31 overexpression effectively reversed the NLRP3 inflammasome activation in Trim31 cKO mice with HF. Selective inhibition of the NLRP3 inflammasome with the NLRP3 inhibitor MCC950 effectively reversed the worsened cardiac dysfunction, hypertrophy, and fibrosis observed in Trim31 cKO mice with HF. Overall, the findings from this study reveal a crucial role of Trim31 in HF. Trim31 deficiency may contribute to the progression of HF by promoting cardiac hypertrophy, fibrosis, and inflammation by facilitating the activation of the NLRP3 inflammasome. Therefore, Trim31 may hold significant potential as a therapeutic target for the treatment of HF.

Background Diffuse large B-cell lymphoma (DLBCL), the most prevalent type of non-Hodgkin’s lymphoma, exhibits significant correlations with efferocytosis-related molecules (ERMs) concerning invasion, metastasis, and clinical outcomes. This study aims to establish an efferocytosis-related gene signature specifically linked to DLBCL. Methods Key module genes linked to DLBCL were identified via weighted gene co-expression network analysis (WGCNA) in GSE32018. Univariate Cox analysis of GSE31312 revealed ERMs associated with DLBCL survival. Differential expression analysis identified differentially expressed genes (DEGs) between DLBCL subtypes and normal samples. Venn diagram analysis identified common DEGs and key module genes. A DLBCL gene signature was built by using univariate Cox and least absolute shrinkage and selection operator (LASSO) analysis. Gene functional enrichment, immune microenvironment, and immunotherapy analyses compared two risk subgroups. Prognostic gene expression was validated at the single-cell level. Results In the GSE32018 dataset, 1760 key module genes related to DLBCL were identified. Using GSE31312, 14 ERMs associated with DLBCL prognosis were determined.Then, an ERMs-related prognostic signature, including small nuclear ribonucleoprotein polypeptides B (SNRPB) and centrosomal protein 290 (CEP290), was established. Independent prognostic analysis showed that the RiskScore derived from this signature was a prognostic factor. Significant immune microenvironment differences were observed between two risk subgroups. Additionally, chemotherapeutic drug sensitivity results indicated the signature could predict therapeutic response. Eventually, expression of SNRPB and CEP290 was confirmed in B cells. Conclusion The prognostic signature comprised of SNRPB and CEP290 based on ERMs-DEGs was established, providing a theoretical basis and reference value for DLBCL research.

Acute myeloid leukaemia (AML) was originally an aggressive malignancy of the bone marrow and one of the deadliest forms of acute leukaemia. The 5-year mortality benefit for patients with AML was only 28.3%. Moreover, a large proportion of patients experienced frequent relapses even after remission, thus predicting a bleak prognosis. This research employed differential expression analysis of AML and normal samples sourced from the GSE30029 database, as well as weighted gene co-expression network analysis (WGCNA). We discovered differential golgi apparatus-related genes (DGARGs) specifically associated with AML. Via regressivity analysis and machine learning algorithm, the cancer genome atlas-acute myeloid leukemia (TCGA-AML) cohort developed a prognostic model using characteristic prognostic genes. The performance value of risk score was analysed using Kaplan-Meier (KM) curves and Cox regression. A predictive nomogram was developed to assess the outcome. The association between prognostic trait genes and the immune microenvironment was examined. Finally, immunoactivity and drug susceptibilities were evaluated in various risk groups identified by prognostic signature genes. A total of 77 DGARGs were obtained by differential expression analysis with WGCNA analysis. Following univariate Cox regression and LASSO regression, six prognostic signature genes (ARL5B, GALNT12, MANSC1, PDE4DIP, NCALD and CYP2E1) were utilized to develop a prognostic model. This model was calibrated via KM survival and receiver operating characteristic (ROC) curves, which concluded that it had a predictive impact on the prognosis of AML. Further analysis of the tumour microenvironment in AML patients demonstrated notable variances in immune cell APC_co_inhibition, CCR, Parainflammation, Type_I_IFN_Response, and Type_II_IFN_Response between the high-risk and low-risk groups. A prognostic model was devised in this study using six prognostic genes linked to the Golgi apparatus. The exactness of the model in guiding the prognosis of AML was established. As a result of expression validation, CYP2E1 and GALNT12 will be used as biomarkers to offer fresh insights into the prognosis and treatment of AML patients.

Background： The prognosis for multiple myeloma patients has significantly improved with the introduction of novel agents. Currently, induction treatments that include two or three novel agents, including daratumumab, are commonly used for newly diagnosed multiple myeloma. High-risk cytogenetic abnormalities (HRA) are linked to poor prognosis in multiple myeloma, with patients having two or more HRA considered at ultra-high risk according to the Mayo Clinic's mSMART definition. However, studies that examine the clinical outcomes of these novel agents and the impact of the number of HRA on prognosis of newly diagnosed multiple myeloma (NDMM) patients are still insufficient in a real-world setting. Aim： This study aims to evaluate the clinical outcomes of novel agents and the impact of the number of HRA on the prognosis of NDMM patients. Methods： Clinical data from Sun Yat-Sen University Cancer Center and six other hospitals were retrospectively analyzed for 734 NDMM patients between 2016 and 2023. Among the patients, 134 received daratumumab-based regimens, 337 received IMiD plus proteasome inhibitor (PI) regimens, and 263 received regimens based on either IMiDs or PIs. There were 327 patients without high-risk abnormalities (HRA), 156 with one HRA, and 46 with two or more HRA. In our study, 129 patients had 1q21 gain/amplification (1q21+) only, 19 had both 1q21+ and t(4;14), and 14 had both 1q21+ and t(14;16). Results： The median overall survival (OS) was 70 months (95% CI: 58-NR) for patients who received PI plus IMiDs, not reached for patients who received CD38 monoclonal antibody-based regimens, and 67 months (95% CI: 52-NR) for patients who received either IMiDs or PI. Patients in the IMiDs plus PI group (P=0.0424) and the CD38 group (P=0.0051) exhibited significantly better OS compared to those in the IMiDs or PI group. There was no significant difference in OS between the CD38 group and the IMiDs plus PI group. The median progression-free survival (PFS) was 54 months (95% CI: 43-NR) for the IMiDs plus PI group, 44 months (95% CI: 44-NR) for the CD38 group, and 44 months (95% CI: 38-54) for the IMiDs or PI group. Similar to the OS trend, significantly superior PFS was observed in patients who received the CD38 monoclonal antibody (P=0.0012) or IMiDs plus PI (P=0.0377) compared to those who received either IMiDs or PI alone. Additionally, there was a trend towards improved PFS in the CD38 group compared to the IMiDs plus PI group (P=0.0507). Patients without HRA had significantly superior OS and PFS compared to those with one HRA and those with two or more HRA (P<0.01). Additionally, having two HRA was associated with a worse OS outcome compared to having one HRA (P=0.0368). There was also a trend towards inferior PFS for patients with two HRA compared to those with one HRA (P=0.0787). We also found that transplantation, achieving minimal residual disease (MRD) negativity, and using a CD38 monoclonal antibody only partially mitigated the poor prognosis associated with HRA. Patients with 1q21+ only had significantly better OS compared to those with 1q21+ and either 17p- (P=0.0112) or t(4;14) (P=0.0072). Similarly, patients with 1q21+ only had significantly better PFS compared to those with 1q21+ and 17p- (P=0.0145), and there was a trend towards improved PFS compared to those with 1q21+ and t(4;14) (P=0.0786). Conclusion： A total of 734 patients were included in this study. Patients treated with either a CD38 monoclonal antibody or a combination of IMiDs and PI had significantly better OS and PFS compared to those receiving IMiDs or PI alone. The CD38 monoclonal antibody also provided a PFS advantage over the IMiDs plus PI combination. HRA conferred a worse prognosis than no HRA, and having two HRA conferred a worse prognosis than having one. Patients with two or more HRA had an extremely poor prognosis and should be considered ultra-high risk in multiple myeloma. The CD38 monoclonal antibody, transplantation, and achieving MRD negativity only partially mitigated the poor prognosis in patients with HRA. Additionally, patients with 1q21 gain/amplification (1q21+) only had a significantly worse prognosis compared to those without HRA, and those with 1q21+ plus del17p or t(4;14) had an even worse prognosis compared to those with 1q21+ alone.