Associations of dietary flavonoid intake with the risk of all-cause and cardiovascular mortality in adults.

BACKGROUND AND AIMS: Flavonoids are widely distributed polyphenolic compounds in the diet that possess various health-promoting effects. This study aimed to investigate the association between dietary flavonoid intake and all-cause and cardiovascular mortality in adults. METHODS AND RESULTS: The data on the six main subclasses of flavonoids, including isoflavones, anthocyanidins, flavan-3-ols, flavanones, flavones, and flavonols, were obtained from the 2007-2010 National Health and Nutrition Examination Survey (NHANES) dataset of adults. The participants were followed up until December 30, 2019. Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for dietary flavonoid intake and mortality. The study included a total of 8758 adults (mean age 44.00 years; 47.40% men). A median follow-up of 10.7 years yielded 1113 all-cause deaths and 261 cardiovascular deaths were recorded. In comparison to category 1, category 4 of flavan-3-ols, flavonols, and total flavonoids were associated with lower risks of all-cause mortality, with multivariable-adjusted HRs of 0.71 (95% CI: 0.55-0.92, Ptrend = 0.021), 0.58 (95% CI: 0.45-0.74, Ptrend<0.001), and 0.63 (95% CI: 0.50-0.80, Ptrend = 0.010), respectively. Similarly, higher intake of category 4 flavonoids was associated with a reduced risk of cardiovascular mortality, with HRs of 0.68 (95% CI: 0.29-0.89, Ptrend = 0.035) for flavones, 0.41 (95% CI: 0.22-0.78, Ptrend = 0.001) for flavonols, and 0.54 (95% CI: 0.36-0.80, Ptrend = 0.021) for total flavonoids. CONCLUSION: Dietary flavonoid intake is associated with all-cause and cardiovascular mortality. Increasing dietary flavonoid intake may reduce the risk of death in adults.

Comparison of the efficacy of taxanes with carboplatin and anthracyclines with taxanes in neoadjuvant chemotherapy for stage II-III triple negative breast cancer: a retrospective analysis.

PURPOSE: The neoadjuvant chemotherapy (NACT) regimen for triple negative breast cancer (TNBC) primarily consists of anthracyclines and taxanes, and the addition of platinum-based drugs can further enhance the efficacy. However, it is also accompanied by more adverse events, and considering the potential severe and irreversible toxicity of anthracyclines, an increasing number of studies are exploring nonanthracycline regimens that combine taxanes and platinum-based drugs. METHODS: The retrospective study included 273 stage II-III TNBC patients who received NACT. The AT group, consisting of 195 (71.4%) patients, received a combination of anthracyclines and taxanes, while the TCb group, consisting of 78 (28.6%) patients, received a combination of taxanes and carboplatin. Logistic regression analysis was performed to evaluate the factors influencing pathological complete response (pCR) and residual cancer burden (RCB). The log-rank test was used to assess the differences in event-free survival (EFS) and overall survival (OS) among the different treatment groups. Cox regression analysis was conducted to evaluate the factors influencing EFS and OS. RESULTS: After NACT and surgery, the TCb group had a higher rate of pCR at 44.9%, as compared to the AT group at 31.3%. The difference between the two groups was 13.6% (OR = 0.559, 95% CI 0.326-0.959, P = 0.035). The TCb group had a 57.7% rate of RCB 0-1, which was higher than the AT group's rate of 42.6%. The difference between the two groups was 15.1% (OR = 0.543, 95% CI 0.319-0.925, P = 0.024), With a median follow-up time of 40 months, the TCb group had better EFS (log-rank, P = 0.014) and OS (log-rank, P = 0.040) as compared to the AT group. Clinical TNM stage and RCB grade were identified as independent factors influencing EFS and OS, while treatment group was identified as an independent factor influencing EFS, with a close-to-significant impact on OS. CONCLUSION: In stage II-III triple TNBC patients, the NACT regimen combining taxanes and carboplatin yields higher rates of pCR and significant improvements in EFS and OS as compared to the regimen combining anthracyclines and taxanes.

The Metabolic Functional Feature of Gut Microbiota in Mongolian Patients with Type 2 Diabetes.

The accumulating evidence substantiates the indispensable role of gut microbiota in modulating the pathogenesis of type 2 diabetes. Uncovering the intricacies of the mechanism is imperative in aiding disease control efforts. Revealing key bacterial species, their metabolites and/or metabolic pathways from the vast array of gut microorganisms can significantly contribute to precise treatment of the disease. With a high prevalence of type 2 diabetes in Inner Mongolia, China, we recruited volunteers from among the Mongolian population to investigate the relationship between gut microbiota and the disease. Fecal samples were collected from the Volunteers of Mongolia with Type 2 Diabetes group and a Control group, and detected by metagenomic analysis and untargeted metabolomics analysis. The findings suggest that Firmicutes and Bacteroidetes phyla are the predominant gut microorganisms that exert significant influence on the pathogenesis of type 2 diabetes in the Mongolian population. In the disease group, despite an increase in the quantity of most gut microbial metabolic enzymes, there was a concomitant weakening of gut metabolic function, suggesting that the gut microbiota may be in a compensatory state during the disease stage. ß-Tocotrienol may serve as a pivotal gut metabolite produced by gut microorganisms and a potential biomarker for type 2 diabetes. The metabolic biosynthesis pathways of ubiquinone and other terpenoid quinones could be the crucial mechanism through which the gut microbiota regulates type 2 diabetes. Additionally, certain Clostridium gut species may play a pivotal role in the progression of the disease.

Experimental Study of the Mechanical Properties of Full-Scale Rubber Bearings at 23 °C, 0 °C, and -20 °C.

In this study, the effects of ambient temperature on the horizontal mechanical performance of isolated rubber bearings were investigated using high-speed reciprocating loading methods. A comprehensive series of 54 experimental trials are performed on the full-scale (900 mm-diameter) isolation rubber bearings, encompassing a range of temperatures (-20 °C, 0 °C, and 23 °C), shear pressures (50%, 100%, and 250%), and frequencies (0.20 Hz, 0.25 Hz, and 0.30 Hz). Because the compression-shear tests were conducted at high velocities and pressures (specifically, vertical compressive stress of 15 MPa), the equipment used in these tests was capable of generating substantial inertial and frictional forces. Appropriate correction methodologies for the precise determination of mechanical performance metrics for bearings are presented. Then, a comprehensive investigation of the effects of various loading conditions on the characteristic strength, post-yield stiffness, horizontal equivalent stiffness, and equivalent damping ratio of LRB900 (lead-core rubber bearings 900 mm-diameter) and LNR900 (linear natural rubber bearings 900 mm-diameter) is conducted. The empirical results show a discernible relationship between these characteristics and ambient temperature as the number of loading cycles increases, except for the equivalent damping ratio. Finally, empirical fitting formulations incorporating the influence of ambient temperature are presented for each performance indicator. These formulas are intended to assist designers in performing seismic design analyses by allowing them to take into consideration the effects of ambient temperature comprehensively.

Associations of urinary volatile organic compounds with cardiovascular disease among the general adult population.

This study was to estimate the associations of volatile organic compounds (VOCs) exposure with the prevalence of total and specific cardiovascular disease (CVD) among the general adult population. This cross-sectional study analyzed 15 urinary VOC metabolites in the general population using the 2011-2016 National Health and Nutrition Examination Survey (n = 5,213). The weighted study population with 47.0 years median age, was primarily female (51.2%). The prevalence of total CVD in the overall population was 7.9%. The single-exposure analyzes of AAMA, ATCA, CEMA, CYMA, DHBMA, 3HPMA, and 3MHA +4MHA were significantly associated with increased prevalence of total CVD. Qgcomp regression consistently showed that urinary VOCs-mixed exposure was positively correlated with the prevalence of total and specific CVDs (chronic heart failure, angina, and stroke), and highlighted each VOCs metabolite weights and direction. The similar results were observed for the WQS regression using mixed analysis methods. In conclusion, exposure to VOCs increases CVD prevalence and advances the identification of risk factors for CVD for environmental study.

Optimization-based adaptive trajectory tracking controller design of self-balanced vehicle with asymptotic prescribed performance.

To handle with the nonlinear external disturbances and unmodeled dynamics of self-balanced vehicle (SBV), a novel adaptive trajectory tracking controller based on asymptotic prescribed performance is proposed. First, a velocity planner based on kinematic is constructed to control the velocity signal to improve the motion stability of SBV. Second, the prescribed performance function (PPF) is designed to prescribe transient-state and steady-state performances (TSP). Afterwards, an optimization-based predictive control (OPC) is proposed for accurate trajectory tracking of SBV. Furthermore, a modified radial basis function neural network (RBFNN) approximator is developed to compensate the unmodeled dynamics and the nonlinear external disturbances of the SBV. The overall system stability is proved with the help of Lyapunov theorem. Finally, the tracking performance and anti-interference robustness of the proposed control method are verified by comparative numerical simulations.

Engaging stakeholders to level up COPD care in LMICs: lessons learned from the "Breathe Well" programme in Brazil, China, Georgia, and North Macedonia.

BACKGROUND: Effective stakeholder engagement in health research is increasingly being recognised and promoted as an important pathway to closing the gap between knowledge production and its use in health systems. However, little is known about its process and impacts, particularly in low-and middle-income countries. This opinion piece draws on the stakeholder engagement experiences from a global health research programme on Chronic Obstructive Pulmonary Disease (COPD) led by clinician researchers in Brazil, China, Georgia and North Macedonia, and presents the process, outcomes and lessons learned. MAIN BODY: Each country team was supported with an overarching engagement protocol and mentored to develop a tailored plan. Patient involvement in research was previously limited in all countries, requiring intensive efforts through personal communication, meetings, advisory groups and social media. Accredited training programmes were effective incentives for participation from healthcare providers; and aligning research findings with competing policy priorities enabled interest and dialogue with decision-makers. The COVID-19 pandemic severely limited possibilities for planned engagement, although remote methods were used where possible. Planned and persistent engagement contributed to shared knowledge and commitment to change, including raised patient and public awareness about COPD, improved skills and practice of healthcare providers, increased interest and support from clinical leaders, and dialogue for integrating COPD services into national policy and practice. CONCLUSION: Stakeholder engagement enabled relevant local actors to produce and utilise knowledge for small wins such as improving day-to-day practice and for long-term goals of equitable access to COPD care. For it to be successful and sustained, stakeholder engagement needs to be valued and integrated throughout the research and knowledge generation process, complete with dedicated resources, contextualised and flexible planning, and commitment.

Association of flavonoid intake with coronary artery disease risk in the older population based on the National Health and Nutrition Examination Survey.

We investigated the association between flavonoid intake and coronary artery disease (CAD) risk in older adults. Data were extracted from the National Health and Nutrition Examination Survey (age ≥ 70 years; 2007-2010 and 2017-2018; n = 2 417). The total flavonoid and flavonoid subclass intake was calculated using validated food frequency questionnaires. The association between flavonoid intake and CAD risk was examined using generalized linear models with restricted cubic spline models. After multivariate adjustment, anthocyanin intake was positively associated with CAD risk; no significant associations were observed between other flavonoid subcategories and endpoint outcomes. Anthocyanins exhibited a non-linear association with CAD risk, and threshold effect analysis showed an inflection point of 15.8 mg/day for anthocyanins. Per unit increase in anthocyanins, the odds of CAD on the left of the inflection point decreased by 2%, while the odds on the right increased by 35.8%. Excessive flavonoid intake may increase CAD risk in the older population.

Circ_0068087 knockdown attenuates high-glucose-induced human tubular epithelial cell injury in a microribonucleic acid/progestin and adipoQ receptor 3-dependent manner in diabetic nephropathy.

AIMS/INTRODUCTION: Previous studies have shown that circular ribonucleic acid mediates the occurrence of diabetic nephropathy. This study aimed to analyze the effects of circ_0068087 on high-glucose (HG)-induced human kidney 2 (HK2) cell dysfunction. MATERIALS AND METHODS: Circ_0068087, miR-580-3p, and progestin and adipoQ receptor 3 (PAQR3) expression were detected by quantitative reverse transcription polymerase chain reaction. Cell viability and proliferation were investigated by Cell Counting Kit-8 and EdU assays, respectively. The cell apoptotic rate was assessed by flow cytometry. Inflammatory response was assessed by enzyme-linked immunoassays. Oxidative stress was evaluated by a superoxide dismutase activity assay kit and lipid peroxidation malondialdehyde assay kit. Molecular interaction was identified by dual-luciferase reporter assay. RESULTS: Circ_0068087 and PAQR3 expression were significantly upregulated in diabetic nephropathy patients. HG treatment inhibited HK2 cell proliferation, but induced cell apoptosis, inflammation, oxidative stress and epithelial-mesenchymal transition by regulating circ_0068087. Circ_0068087 acted as a microribonucleic acid-580-3p (miR-580-3p) sponge, and miR-580-3p targeted PAQR3. Furthermore, circ_0068087 depletion repressed PAQR3 expression through miR-580-3p. MiR-580-3p inhibitors or PAQR3 introduction attenuated circ_0068087 silencing mediated-effects in HG-treated HK2 cells. CONCLUSION: Circ_0068087 promoted HG-induced HK2 cell injuries by the regulation of the miR-580-3p/PAQR3 pathway.

CircTAOK1 regulates high glucose induced inflammation, oxidative stress, ECM accumulation, and apoptosis in diabetic nephropathy via targeting miR-142-3p/SOX6 axis.

BACKGROUND: Diabetic nephropathy (DN) is a complication caused by diabetes. Circular RNAs (circRNAs) are a kind of RNA with a closed circular structure, which has high stability and is involved in many disease-related processes. The mechanism of circRNA TAO kinase 1 (circTAOK1) in the pathogenesis and development of DN is unclear. METHODS: CircTAOK1, microRNA (miR)-142-3p, and sex-determining region Y-box transcription factor 6 (SOX6) mRNA levels were analyzed by real-time quantitative polymerase chain reaction (RT-qPCR). Cell counting kit-8 (CCK8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to analyze cell proliferation. Cell cycle distribution was detected by flow cytometry. Western blot assay was performed to test B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X (Bax), cleaved-caspase 3, and fibronectin (FN), collagen I (Col I), and collagen IV (Col IV) protein levels. ELISA assay was used to measure interleukin 1ß (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor (TNF-α) levels. The reactive oxygen species (ROS) and malondialdehyde (MDA) levels and the superoxide dismutase (SOD) activity were assessed by the corresponding kits. And the correlation between miR-142-3p and circTAOK1 or SOX6 was confirmed by dual luciferase reporter assay, RNA immunoprecipitation assay and RNA pull down assay. RESULTS: CircTAOK1 and SOX6 expression levels were up-regulated, while miR-142-3p expression was down-regulated in DN serum and HG-treated HK-2 cells. Knockdown of circTAOK1 could inhibit cell injury of HG-induced HK-2 cells. The inhibitory effect of circTAOK1 knockdown on HG-induced HK-2 cell injury was restored by miR-142-3p downregulation. CircTAOK1 acted as a sponge for miR-142-3p, and SOX6 was targeted by miR-142-3p. The overexpression of SOX6 could recover the effect of miR-142-3p overexpression on HG-induced HK-2 cell injury. CircTAOK1 regulated the expression of SOX6 by targeting miR-142-3p. CONCLUSION: CircTAOK1 knockdown inhibited HG-induced HK-2 cell damage in DN by the miR-142-3p/SOX6 axis.

Educational efficacy of medical humanities in empathy of medical students and healthcare professionals: a systematic review and meta-analysis.

BACKGROUND: Medical humanities education is an important part of medical education. The purpose of this study was to determine the effectiveness of medical humanities in improving empathy among medical students and healthcare professionals. METHODS: PubMed, Embase, EBSCO-ERIC, Web of Science were searched systematically for studies in the English language. The last retrieval date is May 1, 2023. Best Evidence Medical Education (BEME) Global Rating Scale and Kirkpatrick-based results were used to evaluate the quality of literature. In this study, a meta-analysis of continuous data was conducted. RESULTS: The pooled results by single-arm test meta-analysis showed a benefit with medical humanities programs in empathy (SMD 1.33; 95% CI 0.69-1.96). For single-arm trials of medical humanities program interventions of less than 4 months, 4 months to 12 months, and more than one year, the standardized mean differences(SMD) between post-test and pre-test were 1.74 (P < 0.05), 1.26 (P < 0.05), and 0.13 (P = 0.46), respectively. The results showed a significant difference in the effect of medical humanities programs on male and female empathy (SMD - 1.10; 95% CI -2.08 - -0.13). The SMDs for the study of course, the course combined reflective writing, and the course combined reflective writing and practice as intervention modalities for medical humanities programs were 1.15 (P < 0.05), 1.64 (P < 0.05), and 1.50 (P < 0.05), respectively. CONCLUSION: Medical humanities programs as a whole can improve the empathy of medical students and health professionals. However, different intervention durations and different intervention methods produce different intervention effects.

Unifying and Suppressing Conduction Losses of Polymer Dielectrics for Superior High-Temperature Capacitive Energy Storage.

Superior high-temperature capacitive performance of polymer dielectrics is critical for the modern film capacitor demanded in the harsh-environment electronic and electrical systems. Unfortunately, the capacitive performance degrades rapidly at elevated temperatures owing to the exponential growth of conduction loss. The conduction loss is mainly composed of electrode and bulk-limited conduction. Herein, the contribution of surface and bulk factors is unified to conduction loss, and the loss is thoroughly suppressed. The experimental results demonstrate that the polar oxygen-containing groups on the surface of polymer dielectrics can act as the charge trap sites to immobilize the injected charges from electrode, which can in turn establish a built-in field to weaken the external electric field and augment the injection barrier height. Wide bandgap aluminum oxide (Al2 O3 ) nanoparticle fillers can serve as deep traps to constrain the transport of injected or thermally activated charges in the bulk phase. From this, at 200 °C, the discharged energy density with a discharge-charge efficiency of 90% increases by 1058.06% from 0.31 J cm-3 for pristine polyetherimide to 3.59 J cm-3 for irradiated composite film. The principle of simultaneously inhibiting the electrode and bulk-limited conduction losses could be easily extended to other polymer dielectrics for high-temperature capacitive performance.

A human health risk assessment of rare earth elements through daily diet consumption from Bayan Obo Mining Area, China.

Rare earth elements (REEs) have been broad application in a range of industries, including the electronics industry, advanced materials, and medicine. However, health risks associated with REEs received increasing attention. 31 residents (16 males and 15 females) from Bayan Obo mining in Inner Mongolia, China, were enrolled in this study. In total, 677 food samples, the major human exposure matrices (drinking water and duplicate diets), and bio-samples (urine and blood) of 31 participants were obtained. The concentrations of REEs were measured to characterize their external and internal exposures, and the potential health risk of exposure to REE through the ingestion route was analyzed. The results revealed that the detection rate in blood samples (100%) is higher than in urine (32.86%), and only a few REEs were detected in water samples (8.06%), the urine concentrations were considerably lower than in blood. Exposure to REEs through drinking water was considered negligible compared to food intake. Lanthanum and cerium were the most concentrated REEs in food samples. Health risks were calculated based on a dose-response model, the total hazard quotients (THQ) values for all food groups were within normal levels, and the Monte Carlo simulation results show that the 5th, the 50th, and the 95th percentile values of HI were found as 1.45 × 10-2, 3.52 × 10-2, and 9.13 × 10-2, respectively, neither exceeds the threshold, indicating low health risks associated with food intake exposure for this area. The sensitivity results suggest that underweight people are at higher risk, cerium, lanthanum, and yttrium concentrations, and food intake contributes more to health risks. The use of probability distribution methods can improve the accuracy of the results. The cumulative health risk through food intake is negligible, and further attention should be paid to the health risk induced by other routes of exposure to REEs by the local residents.

Associations of urinary di(2-ethylhexyl) phthalate metabolites with lipid profiles among US general adult population.

Background: Di(2-ethylhexyl) phthalate (DEHP) a parent compound that is metabolized into 4 phthalate metabolites, which correlate to adverse cardio-metabolic risk factors. This study aimed to explore the links between urinary DEHP metabolites and serum lipids in the U.S. general adult population. Methods: In this cross-sectional study, data on 11 urinary phthalate metabolites from the 2005-2018 National Health and Nutrition Examination Surveys (NHANES) were analyzed. Multivariate linear regression and restricted cubic spline (RCS) were used to examine the relationship between phthalate metabolites [specific DEHPs: mono-(2-ethyl-5-carboxy-pentyl) phthalate (MECPP), mono-(2-ethyl-5-hydroxy-hexyl) phthalate (MEHHP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-oxo-hexyl) phthalate (MEOHP)] and serum lipids (triglycerides [TG], total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], and high-density lipoprotein cholesterol [HDL-C]). To identify mixed exposure effects of phthalate metabolites, quantile g-computation (QG-C) and weighted quantile sum (WQS) regression were employed for the lipid profiles. Results: A total of 9141 adults were included in the analysis. MECPP, MEHHP, MEHP, and MEOHP in the highest quartile had a negative relationship with HDL-C compared to the lowest quartile (All P for trend <0.05). TG showed a significant positive relation with MECPP, MEHHP, and MEOHP (All P for trend <0.05), but there was no notable association with MEHP. RCS demonstrated a linear relationship of DEHP metabolites with HDL-C, TC, TG, and LDL-C (all P for nonlinearity >0.05). The WQS index of DEHP metabolites showed independent correlations with HDL-C [ß = -0.26, 95%CI (-0.43, -0.09), P = 0.002], TC [ß = 0.55, 95%CI (0.13, 0.98), P = 0.011], and TG [ß = 2.40, 95%CI (0.85, 3.96), P = 0.003]. Conclusion: Our study suggests that environmental DEHP exposure may affect serum HDL-C and TG levels in the general adult population. Further research is warranted to confirm these findings and illuminate the underlying mechanisms of DEHP exposure on lipids.

Association of Blood Trace Elements Levels with Cardiovascular Disease in US Adults: a Cross-Sectional Study from the National Health and Nutrition Examination Survey 2011-2016.

We aimed to explore the overall association between trace elements and cardiovascular disease (CVD) and its types in humans. A total of 5101 participants' blood samples from the 2011-2016 National Health and Nutrition Examination Survey were included. Biochemical data were collected from laboratory tests conducted at mobile screening centers. After assessing linearity, weighted logistic regression estimated the association between trace elements and various CVD types. Weighted quantile sum (WQS) regression and quantile-based g-computation (Qgcomp) evaluated the overall relationship between biological trace elements and CVD types. After fully adjusting for confounding factors, the odds ratios of overall CVD morbidity corresponding to the second, third, and fourth quartiles of higher selenium (Se) concentration were 0.711 (95% CI, 0.529-0.956, p = 0.024), 0.734 (95% CI, 0.546-0.987, p = 0.041), and 0.738 (95% CI, 0.554-0.983, p = 0.038), respectively. Moreover, an increase in the concentration of copper (Cu) was associated with an increased risk of stroke (95% CI, 1.012-1.094, p = 0.01), heart failure (95% CI, 1.001-1.095, p = 0.046), and heart attack (95% CI, 1.001-1.083, p = 0.046). As the concentration of trace elements in the body increased, there was a significant positive association between Cu and CVD prevalence. On the other hand, Se and zinc were negatively associated with CVD prevalence. A nonlinear relationship between Se and CVD was found, and an appropriate Se intake may reduce the risk of CVD. Cu levels positively correlated with CVD risk. However, prospective cohort studies are warranted to confirm the causal effects of the micronutrients on CVD and its types.

Integrated Bioinformatic Analyses Reveal Immune Molecular Markers and Regulatory Networks for Cerebral Ischemia-Reperfusion.

BACKGROUND: Cerebral ischemia-reperfusion injury (CIR) following a stroke results in secondary damage and is a leading cause of adult disability. The present study aimed to identify hub genes and networks in CIR to explore potential therapeutic agents for its treatment. METHODS: Differentially expressed genes based on the GSE23163 dataset were identified, and weighted gene co-expression network analysis was performed to explore co-expression modules associated with CIR. Hub genes were identified by intersecting immune gene profiles, differentially expressed genes, and modular genes. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and transcription factor-microRNA-gene regulatory network analyses were then conducted in selected crucial modules. Subsequently, their expression levels in animal models were verified using real-time quantitative polymerase chain reaction and Western blotting. Finally, potential drug molecules were screened for, and molecular docking simulations were performed to identify potential therapeutic targets. RESULTS: Seven hub genes-namely, Ccl3, Ccl4, Ccl7, Cxcl1, Hspa1a, Cd14, and Socs3-were identified. Furthermore, we established a protein interaction network using the STRING database and found that the core genes selected through the cytohubba plugin remained consistent. Animal experiments showed that at the transcriptional level, all seven genes showed significant differences (p < 0.001, fold change vs sham, 5-200). At the translational level, however, only Ccl3, Ccl4, Ccl7, Hspa1a, and Socs3 showed significant differences, while Cxcl1 and Cd14 did not. Nifedipine, with the highest predicted score, was identified as a therapeutic agent and successfully docked with the protein encoded by the hub genes. CONCLUSIONS: The expression of Ccl3, Ccl4, Ccl7, Hspa1a, and Socs3 was significantly different in CIR tissues compared to normal tissues both at the transcriptional and translational levels. Systems biology approaches indicated that these could be possible CIR marker genes, providing a stepping stone for further experimental studies.

Application of graph auto-encoders based on regularization in recommendation algorithms.

Social networking has become a hot topic, in which recommendation algorithms are the most important. Recently, the combination of deep learning and recommendation algorithms has attracted considerable attention. The integration of autoencoders and graph convolutional neural networks, while providing an effective solution to the shortcomings of traditional algorithms, fails to take into account user preferences and risks over-smoothing as the number of encoder layers increases. Therefore, we introduce L1 and L2 regularization techniques and fuse them linearly to address user preferences and over-smoothing. In addition, the presence of a large amount of noisy data in the graph data has an impact on feature extraction. To our best knowledge, most existing models do not account for noise and address the problem of noisy data in graph data. Thus, we introduce the idea of denoising autoencoders into graph autoencoders, which can effectively address the noise problem. We demonstrate the capability of the proposed model on four widely used datasets and experimentally demonstrate that our model is more competitive by improving up to 1.3, 1.4, and 1.2, respectively, on the edge prediction task.

Apatinib plus etoposide in pretreated patients with advanced triple-negative breast cancer: a phase II trial.

BACKGROUND: Treatment options for pretreated triple-negative breast cancer (TNBC) are limited. This study aimed to evaluate the efficacy and safety of apatinib, an antiangiogenic agent, in combination of etoposide for pretreated patients with advanced TNBC. METHODS: In this single-arm phase II trial, patients with advanced TNBC who failed to at least one line of chemotherapy were enrolled. Eligible patients received oral apatinib 500 mg on day 1 to 21, plus oral etoposide 50 mg on day 1 to 14 of a 3-week cycle until disease progression or intolerable toxicities. Etoposide was administered up to six cycles. The primary endpoint was progression-free survival (PFS). RESULTS: From September 2018 to September 2021, 40 patients with advanced TNBC were enrolled. All patients received previous chemotherapy in the advanced setting, with the median previous lines of 2 (1-5). At the cut-off date on January 10, 2022, the median follow-up was 26.8 (1.6-52.0) months. The median PFS was 6.0 (95% confidence interval [CI]: 3.8-8.2) months, and the median overall survival was 24.5 (95%CI: 10.2-38.8) months. The objective response rate and disease control rate was 10.0% and 62.5%, respectively. The most common adverse events (AEs) were hypertension (65.0%), nausea (47.5%) and vomiting (42.5%). Four patients developed grade 3 AE, including two with hypertension and two with proteinuria. CONCLUSIONS: Apatinib combined with oral etoposide was feasible in pretreated advanced TNBC, and was easy to administer. CLINICAL TRIAL REGISTRATION: Chictr.org.cn, (registration number: ChiCTR1800018497, registration date: 20/09/2018).