Efficacy and safety of venetoclax-based regimens for the treatment of relapsed/refractory multiple myeloma: a systemic review and meta-analysis.

Background: Patients with relapsed/refractory multiple myeloma (RRMM) usually have dismal prognostic outcomes. Venetoclax, a selective inhibitor of antiapoptotic protein B-cell lymphoma-2 (BCL-2), demonstrates antimyeloma activity in plasma cells with t(11;14) or high BCL-2 expression. Objectives: This meta-analysis aimed to investigate the efficacy and safety of venetoclax-based therapy in RRMM. Design: This is a meta-analysis study. Data Sources and Methods: PubMed, Embase, and Cochrane were searched for studies published up to 20 December 2021. Overall response rate (ORR), rate of very good partial response or better (≧VGPR), and complete response (CR) rate were pooled with the random-effects model. Safety was evaluated by the incidences of grade ≧3 adverse events. Subgroup analysis and meta-regression were performed to identify the causes of heterogeneities. All the analyses were conducted by STATA 15.0 software. Results: A total of 14 studies with 713 patients were included for analysis. The pooled ORR, rate of ≧VGPR, and CR for all patients were 59% [95% confidence interval (CI) = 45-71%], 38% (95% CI = 26-51%), and 17% (95% CI = 10-26%), respectively. The median progression-free survival (PFS) ranged from 2.0 months to not reached (NR), and the median overall survival (OS) ranged from 12.0 months to NR. Meta-regression showed that patients treated with more drugs combined or less heavily pretreated had higher response rates. Patients with t(11;14) had superior ORR [relative risk (RR) = 1.47, 95% CI = 1.05-2.07], ≧VGPR (RR = 1.71, 95% CI = 1.12-2.60), CR (RR = 1.86, 95% CI = 1.34-2.57), PFS [hazard ratio (HR) = 0.47, 95% CI = 0.30-0.65], and OS (HR = 0.30, 95% CI = 0.08-0.52) compared with patients without t(11;14). Most grade ≧3 adverse events were hematologic, gastrointestinal, and infectious related and were manageable. Conclusion: Venetoclax-based therapy is an effective and safe option for RRMM patients, especially those with t(11;14).

Endogenous retroviruses Suppressyn and Syncytin-2 as innovative prognostic biomarkers in Acute Myeloid Leukemia.

Introduction: Emerging evidence has proven that human endogenous retroviruses (HERVs) play a critical role in the pathogenesis of Acute Myeloid Leukemia (AML), whereas the specific HERVs influencing the prognosis of AML patients have yet to be fully understood. Methods: In this study, a systematic exploration was achieved to identify potential prognostic HERVs for AML, sourced from TCGA and GTEx database. Differential analysis and functional enrichment studies were conducted using GO, KEGG, GSEA, and GSVA. The ESTIMATE algorithm was applied to explore the immune infiltration of HERVs in AML. A prognostic risk-score model was evaluated with predicted yearly accuracy using ROC analysis. Results: Two HERVs Suppressyn and Syncytin-2, were identified as promising prognostic biomarkers, with high discrimination ability based on ROC analysis between AML and healthy cohorts from TCGA. Their expression was notably higher in AML patients compared to those in healthy individuals but correlates with favorable clinical outcomes in sub-groups such as white race, lower WBC counts, favorable and intermediate risks, and NPM1 or IDH1 mutation. Suppressyn and Syncytin-2 participated in immune-related pathways and exhibited correlations with multiple immune infiltration cells, such as T cells, mast cells, and tumor-associated macrophages. Finally, we developed a prognostic risk-scoring model combining Suppressyn and Syncytin-2, where a high risk-score is associated with better prognosis. Discussion: Collectively, our findings revealed that Suppressyn and Syncytin-2 may act as valuable diagnostic and prognostic biomarkers for individuals with AML, while highlighting links between HERV activation, immunogenicity, and future therapeutic targets.

Effects of Substrate Surface Characteristics on the Adhesion Properties of Geopolymer Coatings.

Geopolymer is a kind of material with a better ability of high-temperature and corrosion resistance. Poor adhesion could easily lead to problems such as coating cracks, peeling at an early stage, and inability to work with the substrate. The adhesion depends on many factors such as chemical composition of the raw materials, the formulation of the geopolymer, the type of substrate, surface roughness of the substrate, etc. The higher the Si/Al ratio, the greater the shear strength of the coating. This is because geopolymers synthesized with different Si/Al ratios have different phases in the geopolymer binder. Each study uses different multi-parameter combinations selected by itself, which is not uniform and has no universal applicability. As the parameter Ra is determined by the profile centerlines of the substrate surface, it is difficult to get an appropriate value of Ra to represent the roughness of the substrate surface. The parameter-relative area, determined by area scale fractal analysis, can effectively characterize the surface roughness, predict the texture component of bond strength, and establish a connection between which and the bonding performance of the geopolymer coating at a high level of confidence. The bonding strength reduces with the decrease in the value of the relative area. The magnitude of scale employed should be seriously determined when characterizing the surface roughness.

[The Risk Factors of Thrombosis in Patients with Philadelphia Chromosome-negative Myeloproliferative Neoplasms].

OBJECTIVE: To investigate the overview of thrombosis in myeloproliferative neoplasms(MPN) patients, and to explore the risk factors of thrombosis at diagnosis and during follow-up. METHODS: The clinical data of 388 MPN patients treated in our hospital were collected. The patients were followed up by outpatient and phone. The risk factors of thrombosis were analyzed by statistical methods. RESULTS: Among 388 MPN patients, 161 patients (41.49%) showed thromboses at diagnosis or during follow-up. Among them, 92.55% were arterial thromboses, 146 cases (96.27%) were complicated with thromboses at diagnosis, and 36 cases (11.46%) showed newly thromboses or progression of previous thromboses among the 314 received full follow-up patients. Age (P＜0.001, HR:1.033, 95%CI:1.016-1.051), JAK2V617F mutation (P=0.037, HR:1.72, 95%CI: 1.033-2.862), hypertension (P＜0.001, HR:2.639, 95%CI:1.659-4.197) and hyperlipidemia (P＜0.001, HR:2.659, 95%CI:1.626-4.347) were the independent risk factors affecting thrombosis at diagnosis of the patients. During the follow-up, age (P=0.016, HR:1.032, 95%CI: 1.006-1.059) and previous thrombosis history (P=0.019, HR:2.194, 95%CI: 1.135-4.242) were the independent risk factors affecting the progression of thrombosis at different sites or on the basis of the previous thrombosis in the patients. CONCLUSION: Patients with advanced age, JAK2V617F mutation or complicated with hypertension and hyperlipidemia shows a higher risk of thrombosis at diagnosis, while the patients with advanced age or previous thrombosis history shows a higher risk of progression of thrombosis during the follow-up.

Review on the Adhesion of Geopolymer Coatings.

Geopolymers are considered to be green materials with excellent fire resistance performance and potential substitutes for ordinary Portland cement (OPC). This review article focuses on the adhesion of geopolymer coatings subjected to elevated temperature. Their high adhesion strength is the basis for geopolymers being used as coating materials to work with the substrate. The adhesion strength is related to many factors, such as chemical composition of the raw materials, the formulation of the geopolymer, substrate type, surface roughness of the substrate, etc. The Si/Al ratio has different effects on compressive strength and bonding strength. The water content affects the polymerization process-the adhesion strength decreases with increasing water content. Careful tailoring of the mix ratio design is essential to make the geopolymer coating have excellent adhesive performance. These mix design factors include Si/Al ratio, Al/Na ratio, water content, precursor type, alkali cation type, curing conditions, etc.

[Clinical Analysis of 269 Ph Chromosome-Negative Myeloproliferative Neoplasms Patients Stratified by Age].

OBJECTIVE: To investigate the difference of clinical characteristics between young patients(age≤40 years old) and middle-older patients(age>40 years old) with the myeloproliferative neoplasms（MPN）. METHODS: The clinical data (gene mutations， peripheral blood routine examinations， imaging examination and past history) of 269 MPN patients was collected and analyzed. RESULTS: In essential thrombocythemia (ET) group, the proportion of triple-negative type in young patients was higher than that in middle-older group, while the peripheral white blood cell（WBC） and platelets（PLT） counts in the first visit were lower. In polycythemia vera (PV) group, the total detection rate of JAK2V617F (80.65%) was lower than that of other research reports. Young patients with PV showed the lower JAK2V617F rate and lower WBC count, compared with the middle-older aged patients. Both CALR and MPL mutations were not found in PV patients. There was only 1 primary myelofibrosis (PMF) patient aged <40 years old. 91.67% of the patients merged splenomegaly and this rate was higher than that of ET or PV patients. It was found that there were a diagnosed familial MPN family and an undiagnosed family， and the youngest patient was only 8 years old. The second-generation gene sequencing detection for them was not carried out. CONCLUSION: Age is an important reference index in the assessment of risks. The MPN patients with different age and types show much difference in gene mutations, peripheral blood cell counts, thrombotic events and sizes of spleen. The onset ages of patients with familial MPN trends to be generational younger.