Assessment of prolonged proteasome inhibition through ixazomib-based oral regimen on newly diagnosed and first-relapsed multiple myeloma: A real-world Chinese cohort study.

OBJECTIVE: To evaluate the effectiveness, safety, and convenience of in-class transition (iCT) from intravenous bortezomib-based induction to ixazomib-based oral regimens. METHODS: This retrospective real-world study was conducted in 16 Chinese hospitals between October 2017 and April 2023 and analyzed newly diagnosed (NDMM) and first-line relapsed multiple myeloma (FRMM) patients who attained at least a partial response from bortezomib-based induction therapy, followed by an ixazomib-based oral regimen for 2 year or until disease progression or intolerable toxicity. RESULTS: The study enrolled 199 patients, median age: 63 years old, male 55.4%, 53% as high risk (HR), and 47% as standard risk. Cytogenetic risk stratification by metaphase fluorescence in situ hybridization (M-FISH), based on the Mayo Clinic risk stratification system. The median duration of total PI therapy was 11 months, with ixazomib-based treatment spanning 6 months. At the 20-month median follow-up, 53% of patients remained on therapy. The 24-month PFS rate was 84.3% from the initiation of bortezomib-based induction and 83.4% from the start of ixazomib-based treatment. Overall response rate (ORR) was 100% post-bortezomib induction and 90% following 6 cycles of the ixazomib-based regimen. Based on the Sankey diagrams, 89.51% of patients maintained or improved their disease response after 2 cycles of iCT, 6 cycles (90.14%), and 12 cycles (80%). The HR level of Mayo was found to be a significant independent factor in a worse remission (hazard ratio (HR) 2.55; p = 0.033). Ixazomib's safety profile aligned with previous clinical trial data, with 49% of patients experiencing at least one AE of any grade. The most common AEs included peripheral neuropathy, nausea and vomiting, diarrhea, thrombocytopenia, and granulocytopenia. CONCLUSION: In the real-world Chinese MM population, NDMM and FRMM patients responded favorably to PI-based continuous therapy, demonstrating substantial response rates. The ixazomib-based iCT allows for sustained PI-based treatment, offering promising efficacy and tolerable AEs.

Assessment of genetic diversity and variety identification based on developed retrotransposon-based insertion polymorphism (RBIP) markers in sweet potato (Ipomoea batatas (L.) Lam.).

Sweet potato, a dicotyledonous and perennial plant, is the third tuber/root crop species behind potato and cassava in terms of production. Long terminal repeat (LTR) retrotransposons are highly abundant in sweet potato, contributing to genetic diversity. Retrotransposon-based insertion polymorphism (RBIP) is a high-throughput marker system to study the genetic diversity of plant species. To date, there have been no transposon marker-based genetic diversity analyses of sweet potato. Here, we reported a structure-based analysis of the sweet potato genome, a total of 21555 LTR retrotransposons, which belonged to the main LTR-retrotransposon subfamilies Ty3-gypsy and Ty1-copia were identified. After searching and selecting using Hidden Markov Models (HMMs), 1616 LTR retrotransposon sequences containing at least two models were screened. A total of 48 RBIP primers were synthesized based on the high copy numbers of conserved LTR sequences. Fifty-six amplicons with an average polymorphism of 91.07% were generated in 105 sweet potato germplasm resources based on RBIP markers. A Unweighted Pair Group Method with Arithmatic Mean (UPGMA) dendrogram, a model-based genetic structure and principal component analysis divided the sweet potato germplasms into 3 groups containing 8, 53, and 44 germplasms. All the three analyses produced significant groupwise consensus. However, almost all the germplasms contained only one primary locus. The analysis of molecular variance (AMOVA) among the groups indicated higher intergroup genetic variation (53%) than intrapopulation genetic variation. In addition, long-term self-retention may cause some germplasm resources to exhibit variable segregation. These results suggest that these sweet potato germplasms are not well evolutionarily diversified, although geographic speciation could have occurred at a limited level. This study highlights the utility of RBIP markers for determining the intraspecies variability of sweet potato and have the potential to be used as core primer pairs for variety identification, genetic diversity assessment and linkage map construction. The results could provide a good theoretical reference and guidance for germplasm research and breeding.

Rapid subtyping of H9N2 influenza virus by a triple reverse transcription polymerase chain reaction.

The aim of this study was to develop a rapid, cost-saving triple reverse transcription polymerase chain reaction (triple RT-PCR) for subtyping H9N2 avian influenza viruses (AIVs). The three primer pairs for amplification of target sequences of nucleoprotein (NP), hemagglutinin (HA) and neuraminidase (NA) genes, respectively, were designed for subtyping the viruses in the triple RT-PCR. The sensitivity of triple RT-PCR was found to be 10(2) copies per reaction for each of NP, H9 and N2 gene. The specificity tests indicated that all of NP, HA and NA genes were positive for H9N2, only NP gene was positive for H5N1 and H1N1 AIVs, and the results were negative for the other avian viruses including Newcastle disease virus, infectious bronchitis virus, infectious bursal disease virus, duck hepatitis virus and avian encephalomyelitis virus. A total of 112 clinical samples were evaluated by the assay and the results showed that the sensitivity and specificity of triple RT-PCR were in accordance with the virus isolation. In conclusion, this method is rapid and cost-effective making it feasible and attractive for large-scale epidemiological investigation of H9N2 influenza virus.