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.

Application value of structured psychological nursing combined group health education in blood purification patients: Assisted by the purification of a nanofiber composite.

To explore the research value of structured psychological nursing combined with group health education in patients with blood purification. From May 2020 to March 2022, 96 pure-blood patients in the hospital were selected and divided into research group and control group according to simple random classification, with 48 patients in each group. The control group received routine nursing, and the study group conducted health education combined with structured psychological nursing on the basis of usual care. The disease cognitive ability, negative emotions, blood purification adequacy rate, nutritional status qualification rate and complication rate of the two groups before and after intervention were counted. (1) The number of disease points with unclear status in the study group after intervention was 10.39 ± 1.87, complications were 13.88 ± 2.27, lack of disease information was 12.36 ± 2.16, and unpredictability was 9.58 ± 1.38, which were lower than 13.12 ± 2.53, 17.56 ± 2.53, 15.83 ± 3.0411.67 ± 1.71; (2) After the intervention, the values of SDS of 40.77 ± 3.69 and SAS of 41.52 ± 4.06 were lower than those of 45.82 ± 5.01 and 46.35 ± 4.81 in the control group. (3) The blood adequacy rate of the study group was 91.67%, and the nutritional qualification rate was 93.75%, and the data of both groups were higher than that of 77.08% and 79.17% of the control group. (4) The incidence of complications in the study group was 4.17%, and the control group was 16.67%. Group health education and structured psychological care can effectively alleviate patients' negative emotions and deepen their awareness of diseases, thereby improving blood purification rate and nutrient absorption.

Occurrence, bioaccumulation, fate, and risk assessment of novel brominated flame retardants (NBFRs) in aquatic environments - A critical review.

Novel brominated flame retardants (NBFRs), which have been developed as replacements for legacy flame retardants such as polybrominated diphenyl ethers (PBDEs), are a class of alternative flame retardants with emerging and widespread applications. The ubiquitous occurrence of NBFRs in the aquatic environments and the potential adverse effects on aquatic organisms have initiated intense global concerns. The present article, therefore, identifies and analyzes the current state of knowledge on the occurrence, bioaccumulation, fates, and environmental and health risks of NBFRs in aquatic environments. The key findings from this review are that (1) the distribution of NBFRs are source-dependent in the global aquatic environments, and several NBFRs have been reported at higher concentrations than that of the legacy flame retardants; (2) high bioaccumulative properties have been found for all of the discussed NBFRs due to their strong hydrophobic characteristics and weak metabolic rates; (3) the limited information available suggests that NBFRs are resistant to biotic and abiotic degradation processes and that sorption to sludge and sediments are the main fate of NBFRs in the aquatic environments; (4) the results of ecological risk assessments have indicated the potential risks of NBFRs and have suggested that source areas are the most vulnerable environmental compartments. Knowledge gaps and perspectives for future research regarding the monitoring, toxicokinetics, transformation processes, and development of ecological risk assessments of NBFRs in aquatic environments are proposed.

Backers investment behavior on explicit and implicit factors in reward-based crowdfunding based on ELM theory.

The aim of this study is to identify the dynamic explicit and implicit information factors which displayed on the webpage of platforms that influence backers' investment decision-making behavior. We analyze the connections among these factors by collecting the longitudinal dataset from reward-based crowdfunding platform. Based on ELM model, we establish Fixed Estimation Panel Data Model respectively according to explicit and implicit factors and take Funding Status (crowdfunding results) as the moderating variable to observe the goal gradient effect. Results indicate that most variables in the central route affect backers' investment behavior positively, while most variables in the periphery route have a negative impact on backers' investment behavior. The Funding Status has a significant negative moderating effect on the explicit variables, and has no significant moderating effect on the implicit information variables of the project. In addition, we upgrade the econometric method used by previous scholars, which could improve the accuracy of the FE model. Furthermore, we find strong support for the herding effect in reward-based crowdfunding and the intensity tends to decrease before the funding goal draws near.

Systematic assessment of tissue dissociation and storage biases in single-cell and single-nucleus RNA-seq workflows.

BACKGROUND: Single-cell RNA sequencing has been widely adopted to estimate the cellular composition of heterogeneous tissues and obtain transcriptional profiles of individual cells. Multiple approaches for optimal sample dissociation and storage of single cells have been proposed as have single-nuclei profiling methods. What has been lacking is a systematic comparison of their relative biases and benefits. RESULTS: Here, we compare gene expression and cellular composition of single-cell suspensions prepared from adult mouse kidney using two tissue dissociation protocols. For each sample, we also compare fresh cells to cryopreserved and methanol-fixed cells. Lastly, we compare this single-cell data to that generated using three single-nucleus RNA sequencing workflows. Our data confirms prior reports that digestion on ice avoids the stress response observed with 37 °C dissociation. It also reveals cell types more abundant either in the cold or warm dissociations that may represent populations that require gentler or harsher conditions to be released intact. For cell storage, cryopreservation of dissociated cells results in a major loss of epithelial cell types; in contrast, methanol fixation maintains the cellular composition but suffers from ambient RNA leakage. Finally, cell type composition differences are observed between single-cell and single-nucleus RNA sequencing libraries. In particular, we note an underrepresentation of T, B, and NK lymphocytes in the single-nucleus libraries. CONCLUSIONS: Systematic comparison of recovered cell types and their transcriptional profiles across the workflows has highlighted protocol-specific biases and thus enables researchers starting single-cell experiments to make an informed choice.

Safety Assessment of Electronic Cigarettes and Their Relationship with Cardiovascular Disease.

Smoking leads to the occurrence and development of a variety of diseases. Most importantly, it is an independent risk factor of cardiovascular atherosclerosis. In recent years, electronic cigarettes have become a popular alternative to traditional cigarettes, since modern micro-electronic techniques provide the possibility of simulating the process of traditional smoking. Additionally, it is convenient and fashionable. Nevertheless, comments about the safety of electronic cigarettes remain controversial. Although the research about electronic cigarettes increased exponentially, there has been no systematic study of its safety. The aim of the current study is to review the literature reports about the safety of electronic cigarettes, and to understand their hazards and disadvantages. It was found that most of the current research about electronic cigarettes comprises short-term and in vitro studies. There are few reports of in vivo and long-term studies. Notably, the level of harmful components such as volatile organic compounds, tobacco-specific nitrosamines and heavy metals in electronic cigarettes are even higher than in traditional cigarettes. Therefore, the harm of electronic cigarettes should not be underestimated. In conclusion, the question of whether electronic cigarettes are a safe and sufficient substitute for traditional smoking needs further investigation.

Oral health survey and oral health questionnaire for high school students in Tibet, China.

OBJECTIVES: The aim of this study is to identify the oral health status as well as oral health practices and access for care of graduating senior high school Tibetan students in Shannan prefecture of Tibet. METHODS: Based on standards of the 3rd Chinese National Oral Epidemiological Survey and WHO Oral Health Surveys, 1907 graduating students from three senior high schools were examined for caries, periodontitis, dental fluorosis, and oral hygiene status. The questionnaire to the students addressed oral health practices and present access to oral medical services. RESULTS: Dental caries prevalence (39.96%) and mean DMFT (0.97) were high in Tibetan students. In community periodontal indexes, the detection rate of gingivitis and dental calculus were 59.50% and 62.64%, respectively. Oral hygiene index-simplified was 0.69, with 0.36 and 0.33 in debris index-simplified and calculus index-simplified, respectively. Community dental fluorosis index was 0.29, with 8.13% in prevalence rate. The questionnaire showed students had poor oral health practices and unawareness for their needs for oral health services. It was also noted that the local area provides inadequate oral medical services. CONCLUSIONS: Tibetan students had higher prevalence of dental diseases and lower awareness of oral health needs. The main reasons were geographical environment, dietary habit, students' attitude to oral health, and lack of oral health promotion and education. Oral health education and local dentists training should be strengthened to get effective prevention of dental diseases.

Noninvasive prenatal diagnosis of common aneuploidies by semiconductor sequencing.

Massively parallel sequencing (MPS) of cell-free fetal DNA from maternal plasma has revolutionized our ability to perform noninvasive prenatal diagnosis. This approach avoids the risk of fetal loss associated with more invasive diagnostic procedures. The present study developed an effective method for noninvasive prenatal diagnosis of common chromosomal aneuploidies using a benchtop semiconductor sequencing platform (SSP), which relies on the MPS platform but offers advantages over existing noninvasive screening techniques. A total of 2,275 pregnant subjects was included in the study; of these, 515 subjects who had full karyotyping results were used in a retrospective analysis, and 1,760 subjects without karyotyping were analyzed in a prospective study. In the retrospective study, all 55 fetal trisomy 21 cases were identified using the SSP with a sensitivity and specificity of 99.94% and 99.46%, respectively. The SSP also detected 16 trisomy 18 cases with 100% sensitivity and 99.24% specificity and 3 trisomy 13 cases with 100% sensitivity and 100% specificity. Furthermore, 15 fetuses with sex chromosome aneuploidies (10 45,X, 2 47,XYY, 2 47,XXX, and 1 47,XXY) were detected. In the prospective study, nine fetuses with trisomy 21, three with trisomy 18, three with trisomy 13, and one with 45,X were detected. To our knowledge, this is the first large-scale clinical study to systematically identify chromosomal aneuploidies based on cell-free fetal DNA using the SSP and provides an effective strategy for large-scale noninvasive screening for chromosomal aneuploidies in a clinical setting.

Impact of the next-generation sequencing data depth on various biological result inferences.

Next-generation sequencing (NGS) technologies have revolutionized the field of genomics and provided unprecedented opportunities for high-throughput analysis at the levels of genomics, transcriptomics and epigenetics. However, the cost of NGS is still prohibitive for many laboratories. It is imperative to address the trade-off between the sequencing depth and cost. In this review, we will discuss the effects of sequencing depth on the detection of genes, quantification of gene expression and discovering of gene structural variants. This will provide readers information on choosing appropriate sequencing depth that best meet the needs of their particular project.