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.

Dietary assessment of type 2 diabetic patients using healthful plant-based diet score in the Eastern Province of Saudi Arabia.

BACKGROUND: Diabetes mellitus is a chronic disease characterized by a wide range of metabolic problems. The current study sought to assess nutritional habits of Saudi patients with type 2 diabetes (T2D) and to propose recommendations to improve these patients' dietary habits and delay possible disease complications. METHODS: Over a period of three years, (2017-2019) 577 patients with T2D attending the outpatient's diabetic clinics at King Fahd Hospital of the University, Al Khobar, Saudi Arabia were invited to participate in this study. Data of dietary intake were collected by trained nurses using a pretested structured validated semi quantitative food frequency questionnaire. The dietary data were collected using 7-day dietary recall questionnaire. A modified score system that associates dietary habits with glycemic control and lipid profile was used. RESULTS: Overall, a high healthful plant-based diet score was associated with a significant (P = 0.018) reduction in triglycerides (TG) level (mean difference - 3.78%; 95% CI, -0.65% to -6.81%) and a statistically non-significant (P = 0.06) increase in high density lipoprotein (HDL) levels (mean difference 1.87%; 95% CI -0.06-3.84%) in T2D patients from the Eastern Province of Saudi Arabia. Additionally, in our patient group, the prevalence of coronary artery disease, stroke, peripheral artery disease, and chronic kidney disease in T2D patients was 11.3%, 6.2%, 3.3%, and 8.4%, respectively and were higher when compared to the prevalence in the general population. CONCLUSION: The present study showed that adherence to a healthful plant-based diet, when compared to high glycemic index diet, is associated with a favorable outcome in glycemic control and lipid profile in T2D patients. Prior assessment of total diet quality may be beneficial when giving nutritional advice to T2D patients with the possibility of improving glycemic control and lipid profile.

[Application of Data Analysis and Data Visualization in Medical Equipment: Take Infusion Pump as Example].

OBJECTIVE: To combine data analysis and data visualization with medical devices, provide a set of data analysis and data visualization solutions. This solutions can deeply excavate the data of the whole life cycle of medical equipment, and then play a guiding role in business. METHODS: With the help of mature tools in the Internet field, YIYI and YOUSHU, we can quickly complete data collection and rich visualization effects, and introduce the concept of data analysis to deeply mine data. RESULTS: Taking the maintenance data of infusion pump as an example, the data collection is completed through YIYI, and the maintenance system is built on YOUSHU. CONCLUSIONS: The maintenance system of infusion pump system is simple and clear, with good visualization effect. It can quickly analyze maintenance failures, reduce maintenance times and maintenance costs, ensure the safety of the equipment. Moreover, the system can be easily transferred to other medical equipment, and can carry on the whole life cycle data research.

Comprehensive geriatric assessment in newly diagnosed older myeloma patients: a multicentre, prospective, non-interventional study.

BACKGROUND: Multiple myeloma is a disease of the older people, whose prognoses are highly heterogeneous. The International Myeloma Working Group (IMWG) proposed a geriatric assessment (GA) based on age, functional status and comorbidities to discriminate between fit and frail patients. Given the multidimensional nature of frailty and the relatively recent exploration of frailty in the field of MM, reaching a consensus on the measurement of frailty in MM patients remains challenging. OBJECTIVE: We sought to assess the feasibility of performing a comprehensive GA (CGA) in older MM patients in a real-world and multicentre setting and to evaluate their baseline CGA profiles. RESULTS: We studied 349 older patients with newly diagnosed MM (age range, 65-86 years). Our results showed that a CGA is feasible for older MM patients. Using the IMWG-GA criteria, we identified significantly more frail patients in our cohort comparing to in the IMWG cohort (43% vs 30%, P = 0.002). In the IMWG-GA 'fit' group, risk of malnutrition, depression and cognitive impairment remains. The median follow-up time was 26 months (range 1-38). The median overall survival (OS) was 34.7 months, and the estimated 3-year OS rate was 50%. A high MNA-SF score (MNA-SF ≥ 12), low GDS score (GDS ≤ 5) and high CCI score (CCI ≥ 2) can be used to predict the OS of older patients with newly diagnosed MM. This study is registered at www.clinicaltrials.gov (NCT03122327). CONCLUSIONS: Our study justifies the need for a CGA in older patients with newly diagnosed MM.

Feelings of loneliness and mental health needs and services utilization among Chinese residents during the COVID-19 epidemic.

BACKGROUND: Due to the implementation of social distancing and quarantine measures, loneliness has been a major public health concern during the COVID-19 pandemic. However, few studies have examined loneliness in Chinese residents during the COVID-19 epidemic, as well as its associations with mental health needs and services utilization. METHODS: The present study was a cross-sectional survey during the COVID-19 outbreak in China. A total of 7741 adults were invited and completed an online self-administered questionnaire. The Chinese 12-item General Health Questionnaire was used to screen for common mental health problems, loneliness was measured with a single-item self-report question ("How often do you feel lonely in recent days?"), and two standardized questions were used to assess perceived needs for and use of mental health services. RESULTS: In total, 24.2 % of the participants felt lonely in recent days. Age of 16-29 years (OR = 1.36, P = 0.020), marital status of never-married (OR = 1.47, P < 0.001), marital status of "others" (re-married, co-habiting, separated, divorced, and widowed) (OR = 1.72, P < 0.001), having infected family members or close relatives (OR = 1.64, P = 0.026), and having infected colleagues, friends, or classmates (OR = 1.62, P < 0.001) were significant correlates of loneliness. Rates of mental health needs (17.4 % vs. 4.9 %, P < 0.001) and services utilization (2.7 % vs. 1.0 %, P < 0.001) were significantly higher in lonely than not lonely participants. After adjusting for socio-demographic and epidemic characteristics and common mental health problems, loneliness was still significantly associated with mental health needs (OR = 2.50, P < 0.001) and services utilization (OR = 1.62, P = 0.020). CONCLUSIONS: Feelings of loneliness are prevalent among Chinese residents affected by the COVID-19 epidemic and the presence of loneliness is associated with high levels of mental health needs and greater services utilization. Effective measures aiming at preventing or reducing loneliness are potentially beneficial for the mental wellbeing of COVID-19-affected population and reducing the use of the limited mental health service resources during the COVID-19 pandemic.

Comprehensive Assessment of Candidate Reference Genes for Gene Expression Studies Using RT-qPCR in Tamarixia radiata, a Predominant Parasitoid of Diaphorina citri.

Tamarixia radiata (Waterston) is a predominant parasitoid of the Asian citrus psyllid (ACP), a destructive citrus pest and vector of huanglongbing (HLB) disease in the fields of southern China. To explore the functioning of target genes in T. radiata, the screening of specific reference genes is critical for carrying out the reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) under different experimental conditions. However, no reference gene(s) for T. radiata has yet been reported. Here, we selected seven housekeeping genes of T. radiate and evaluated their stability under the six conditions (developmental stage, sex, tissue, population, temperature, diet) by using RefFinder software, which contains four different programs (geNorm, ΔCt, BestKeeper, and NormFinder). Pairwise variation was analyzed by geNorm software to determine the optimal number of reference genes during the RT-qPCR analysis. The results reveal better reference genes for differing research foci: 18S and EF1A for the developmental stage; PRS18 and EF1A for sex, PRS18 and RPL13 for different tissues (head, thorax, abdomen); EF1A and ArgK between two populations; ß-tubulin and EF1A for different temperatures (5, 15, 25, 35 °C); and ArgK and PRS18 for different feeding diets. Furthermore, when the two optimal and two most inappropriate reference genes were chosen in different temperatures and tissue treatments, respectively, the corresponding expression patterns of HSP70 (as the reporter gene) differed substantially. Our study provides, for the first time, a more comprehensive list of optimal reference genes from T. radiata for use in RT-qPCR analysis, which should prove beneficial for subsequent functional investigations of target gene(s) in this natural enemy of ACP.

Assessment on the binding affinity between ritonavir with model transport protein: a combined multi-spectroscopic approaches with computer simulation.

The binding affinity between ritonavir (RTV) and model transport protein, BSA was assessed through multi-spectroscopic approaches and computer simulation. The findings revealed RTV statically quenched the fluorescence of BSA and formed the 1:1 RTV-BSA complex with the binding constant (Kb) of 1.06 × 103 ∼ 5.08 × 103 M-1 under the studied temperatures (298 ∼ 310 K). During the interaction of RTV with BSA, the hydrogen bonds and van der Waals forces acted as predominant function while the hydrophobicity played an assistant function. Molecular modeling further verified the result obtained from the competitive binding experiments, RTV preferentially fit into in the sub-domain IIIA of BSA. The perturbation in the secondary structures of BSA upon acting with RTV was observed from IR results, whereas synchronous and 3D fluorescence spectral findings unraveled the slight change in the hydrophobicity surrounding Tyr and Trp residues.Communicated by Ramaswamy H. Sarma.

Assessment on the binding characteristics of dasatinib, a tyrosine kinase inhibitor to calf thymus DNA: insights from multi-spectroscopic methodologies and molecular docking as well as DFT calculation.

The binding characteristics of calf thymus DNA (ct-DNA) with dasatinib (DSTN), a tyrosine kinase inhibitor was assessed through multi-spectroscopic methodologies and viscosity measurement combined with molecular docking as well as DFT calculation to understand the binding mechanism, affinity of DSTN onto ct-DNA, effect of DSTN on ct-DNA conformation, and among others. The results confirmed DSTN bound onto ct-DNA, leading to forming the DSTN-ct-DNA complex with the binding constant of 4.82 × 103 M-1 at 310 K. DSTN preferentially inserted to the minor groove of ct-DNA with rich A-T region, that was the binding mode of DSTN onto ct-DNA was groove binding. The enthalpic change (ΔH0) and entropic change (ΔS0) during the binding process of DSTN with ct-DNA were 128.9 kJ mol-1 and 489.2 J mol-1 K-1, respectively, confirming clearly that the association of DSTN with ct-DNA was an endothermic process and the dominative driven-force was hydrophobic interaction. Meanwhile, the results also indicated that there was a certain extent of electrostatic force and hydrogen bonding, but they maybe play an auxiliary role. The CD measurement results confirmed the alteration in the helical configuration of ct-DNA but almost no change in the base stacking after binding DSTN. The results revealed that there was the obvious change in the conformation, the dipole moment, and the atomic charge distribution of DSTN in the B-DNA complexes, compared with free DSTN, to satisfy the conformational adaptation. From the obtained fronitier molecular orbitals of DSTN, it can be inferred that the nature of DSTN alters with the change of the environment around DSTN. Communicated by Ramaswamy H. Sarma.

Risk Assessment of Two Insecticides on Encarsia formosa, Parasitoid of Whitefly Bemisia tabaci.

The assessment of acute toxicity to insect natural enemies is very important for insecticide selection used within integrated pest management (IPM). The acute toxicity of abamectin and imidacloprid against Encarsia formosa, a parasitoid of Bemisia tabaci, was investigated. Abamectin had a high toxicity risk to E. formosa, while imidacloprid showed a medium toxicity risk. When treated with the lethal concentration 30 (LC30) of abamectin, the dwelling time of E. formosa in B. tabaci infested-plant-area (IPA) was significantly lower than in non-infested plant areas (non-IPA). In addition, the frequency of E. formosa entering into the two areas was not significantly different in the LC10 and LC30 treatments. Within the IPA, LC10, and LC30 treatments decreased the dwelling time and entering frequency of parasitoid significantly. For imidacloprid treatments, E. formosa stayed a longer time in the non-IPA than in the IPA when treated with LC30. The frequency of E. formosa entering into the two areas was only slightly different in the LC1, LC10, and LC30 treatments. Within the IPA, LC10 and LC30 treatments were significantly decreased in the dwelling time and the entering frequency of E. formosa. The results indicate that abamectin and imidacloprid have high or medium acute toxicity against E. formosa and a negative sublethal effect on its searching behaviour.

[A research on the construction of an assessment index system to evaluate the implementation of health promotion in enterprises].

OBJECTIVE: To establish an assessment index system to objectively evaluate the implementation of health promotion in enterprises. METHODS: Multi-methods, which include the reviewing references, the summarizing results of preliminary studies, the interview with experts and employers, were used in developing attentative index framework and working out the consultative questionnaires. Then the improved Delphi Method was adopted in collecting ideas from 20 experts in China, and they scored the importance of every single index by two rounds of consultation. On the basis of these data, the indicators were added , deleted or modified according to concentration and distraction levels of expert ideas. The method of the percentile weighted coefficient was conducted to decide the weighing of assessment index. RESULTS: The responding rates to the two rounds of questionnaires were 90.91% and 100.00% respectively. The overall specialist authoritative coefficient was 0.69, the coordination coefficient of all indicators was 0.623 (P <0.01),and the coordination coefficient of the four kinds of first-ranking indicators was 0.313, 0.625, 0.390, 0.563, respectively (P<0.01).Eventually, an assessment index system consisting of 4 first-ranking indicators and 10 sub-indicators which were further divided into 52 grade-three indicators was set up. CONCLUSION: The assessment index system possesses good content validity, and the liability and typicality were recognized by experts. However, it should be applied and validated in practice.

[Comparison of three different organ failure assessment score systems in predicting outcome of severe sepsis].

OBJECTIVE: To compare multiple organ dysfunction score (MODS), the sequential organ failure assessment (SOFA) and the logistic organ dysfunction score (LODS) in predicting hospital mortality in severe sepsis. METHODS: Four hundred and three patients admitted to the ICU from December 2004 to November 2007 with a diagnosis of severe sepsis were enrolled in this study. Their MODS, SOFA, LODS and Acute Physiology and Chronic Health Evaluation (APACHE) II at admission and the highest score during hospitalization were respectively recorded and collected in regard to mortality. The discrimination of three multiple organ dysfunction score systems were assessed by the areas under the receiver operating characteristic curves (AUC). RESULTS: The AUC of admission scores was 0.811 for LODS, 0.787 for SOFA, 0.725 for MODS, and 0.770 for APACHE II in predicting hospital mortality. All maximum scores had better power of discrimination than the admission scores (P < 0.01). The power of discrimination of LODS and SOFA were better than the MODS, either the admission or the highest, respectively (P < 0.01). However, no significant difference was observed between the LODS and the SOFA regarding mortality prediction (P > 0.05). The AUC value for the APACHE II score was much lower compared to LODS (P < 0.01). However, there was no difference in AUC value among APACHE II, SOFA and MODS (P > 0.05). CONCLUSION: LODS, SOFA and MODS show a good discrimination power, while maximum LODS is of the highest discrimination power to predict the outcome of patient with severe sepsis.

The application of gene therapy in China.

Since the 1990s, gene therapy has been broadly applied in the treatment of life-threatening diseases, including infectious disease, cancer, cardiovascular disease and hereditary diseases. China in particular has become a competitive marketplace for the development of biotechnology and gene therapy products. This article provides an overview of the regulatory guidance for gene therapy research, product development and commercialization in China. The first approved gene therapy product, recombinant human adenoviral p53 injection (Gendicine), is highlighted as an example of the innovation occurring in the field in China.

An alternative approach to synthesize cDNA bypassing traditional reverse transcription.

cDNAs of certain target genes are difficult to obtain by traditional reverse transcription. Herein we describe a novel method to synthesize cDNA based upon the use of the class IIS restriction enzymes. Briefly, the exons of a certain gene are separately PCR-amplified, each using the primers containing a recognition sequence of a certain class IIS restriction enzyme. All the fragments are restricted using the enzyme(s), resulting in the cohesive end of each exon that is complementary to the one in its adjacent exon. Then the fragments can be assembled together in their naturally occurring order. We successfully applied this method to acquire the coding sequence of Hoxa7 gene. This approach is simple, highly efficient, less error prone and cost-effective, and can also be used to fuse different PCR-fragments from distinct genes to create a chimeric gene or to perform site-directed mutagenesis.

Pulmonary surfactant-associated protein A as a marker of respiratory distress in forensic pathology: assessment of the immunohistochemical and biochemical findings.

The aim of the present study was to review the immunohistochemical and biochemical findings with reference to the causes of death in routine casework (total, n=492). In the immunohistochemistry (n=283), an increase in intra-alveolar granular SP-A (SP-A score) was often observed in asphyxiation (n=21/34, 61.8%) and freshwater drowning (n=15/24, 62.5%), and also in fire and methamphetamine (MA) fatalities (n=22/76, 28.9% and n=5/16, 31.3%). Serum SP-A level (n=134) was elevated in acute respiratory distress syndrome and in some cases of drowning, fire and MA fatalities, hyperthermia and chest traumas. A quantitative analysis of SP-A subclass-gene expression (SP-A1/A2 mRNA) in the lung tissue specimens (n=126) revealed an increase in the SP-A1/A2 mRNA ratio in asphyxiation (n=17/21, 80.9%), freshwater drowning (n=7/9, 77.7%), fire and MA fatalities (n=20/35, 57.1% and n=8/10, 80.0%). These findings suggested the usefulness of SP-A as a marker of asphyxiation, respiratory distress and alveolar injury.