Association between abusive supervision and nurses' withholding voice about patient safety: the roles of impression management motivation and speak up-related climate.

BACKGROUND: Abusive supervision by the nurse manager significantly influences nurses' withholding voice about patient safety. The role of impression management motivation and speak up-related climate is crucial in understanding their connection. This study aimed to explore the relationship between abusive supervision, impression management motivation, speak up-related climate, and withholding voice about patient safety. METHODS: This cross-sectional study employed a convenience sampling method to recruit 419 clinical nurses from Taizhou Hospital, Zhejiang Province, China, between 1 November 2022 and 31 January 2023. The study adhered to the STROBE checklist. Abusive supervision and impression management motivation were assessed using the Chinese versions of the Abusive Supervision Scale and the Impression Management Motivation Scale, respectively. Withholding voice about patient safety and speak up-related climate were identified using the Chinese version of the Speaking Up about Patient Safety Questionnaire. RESULTS: Nurse leaders' abusive supervision (ß=0.40, p<0.01) and nurses' impression management motivation (ß=0.10, p<0.01) significantly and positively influenced nurses' withholding voice about patient safety. We introduced impression management motivation as a mediating variable, and the effect of abusive supervision on nurses' withholding voice decreased (ß from 0.40 to 0.38, p< 0.01). Nurses' speak up-related climate played a moderating role between abusive supervision and impression management motivation (ß= 0.24, p<0.05). CONCLUSIONS: Abusive supervision by nursing leaders can result in nurses withholding voice about patient safety out of self-protective impression management motives. This phenomenon inhibits nurses' subjective initiative and undermines their proactive involvement in improving patient safety, and hinders the cultivation of a culture encouraging full participation in patient safety, which should warrant significant attention.

Construed Organizational Ethical Climate and Whistleblowing Behavior: The Moderated Mediation Effect of Person-Organization Value Congruence and Ethical Leader Behavior.

An organizational ethical climate enhances the degree of collaboration and cohesion among employees and facilitates the development and interests of organizations. Such roles lead to organizational sustainable development and survival. Therefore, the importance of ethical climate in organizations is becoming increasingly apparent. In this background, this study aims to explore whether an organizational ethical climate can improve whistleblowing behavior and the mediating role of organizational identification in promoting whistleblowing behavior. Most previous studies have only focused on the mediating or moderating role of the model. This study expands the research field, adds the dual moderation of person-organization value congruence and leader ethical behavior, and verifies two moderated mediation models. Overall, the purpose of this study is to determine the behavior of employees under the influence of an organizational ethical climate and, on this basis, propose suggestions for strengthening organizational ethical climate, expanding the scope of research on organizational climate and providing a theoretical basis for related research. In order to achieve the research goals, the data were collected from 344 Chinese SMEs for empirical analysis. The results showed that an organizational ethical climate has no direct impact on whistleblowing behavior but could have a positive effect on whistleblowing formation through the mediating variable of organizational identification. In addition, person-organization value congruence and leader ethical behavior significantly moderated the mediating role of organizational identification between organizational ethical climate and whistleblowing behavior. Finally, the directions that can contribute to future research were suggested.

Cyanidin-3-O-Glucoside Alleviates Alcoholic Liver Injury via Modulating Gut Microbiota and Metabolites in Mice.

Alcoholic liver disease (ALD) is primarily caused by long-term excessive alcohol consumption. Cyanidin-3-O-glucoside (C3G) is a widely occurring natural anthocyanin with multiple biological activities. This study aims to investigate the effects of C3G isolated from black rice on ALD and explore the potential mechanism. C57BL/6J mice (male) were fed with standard diet (CON) and Lieber-DeCarli liquid-fed (Eth) or supplemented with a 100 mg/kg/d C3G Diet (Eth-C3G), respectively. Our results showed that C3G could effectively ameliorate the pathological structure and liver function, and also inhibited the accumulation of liver lipids. C3G supplementation could partially alleviate the injury of intestinal barrier in the alcohol-induced mice. C3G supplementation could increase the abundance of Norank_f_Muribaculaceae, meanwhile, the abundances of Bacteroides, Blautia, Collinsella, Escherichia-Shigella, Enterococcus, Prevotella, [Ruminococcus]_gnavus_group, Methylobacterium-Methylorubrum, Romboutsia, Streptococcus, Bilophila, were decreased. Spearman's correlation analysis showed that 12 distinct genera were correlated with blood lipid levels. Non-targeted metabolic analyses of cecal contents showed that C3G supplementation could affect the composition of intestinal metabolites, particularly bile acids. In conclusion, C3G can attenuate alcohol-induced liver injury by modulating the gut microbiota and metabolites, suggesting its potential as a functional food ingredient against alcoholic liver disease.

Discovery of a Highly Potent Oxysterol Receptor GPR183 Antagonist Bearing the Benzo[d]thiazole Structural Motif for the Treatment of Inflammatory Bowel Disease (IBD).

Accumulating evidence has demonstrated a critical pathological role of oxysterol receptor GPR183 in various inflammatory and autoimmune diseases, including inflammatory bowel disease (IBD). However, the currently reported GPR183 antagonists are very limited and not qualified for in vivo studies due to their inferior druglike properties. Herein, we conducted a structural elaboration focusing on improving its PK and safety profile based on a reference antagonist NIBR189. Of note, compound 33, bearing an aminobenzothiazole motif, exhibited reduced hERG inhibition, improved PK properties, and robust antagonistic activity (IC50 = 0.82 nM) with high selectivity against GPR183. Moreover, compound 33 displayed strong in vitro antimigration and anti-inflammatory activity in monocytes. Oral administration of compound 33 effectively improved the pathological symptoms of DSS-induced experimental colitis. All of these findings demonstrate that compound 33 is a novel and promising GPR183 antagonist suitable for further investigation to treat IBD.

Whole grain germinated brown rice intake modulates the gut microbiota and alleviates hypertriglyceridemia and hypercholesterolemia in high fat diet-fed mice.

Hyperlipidemia is a common clinical disorder of lipid metabolism in modern society and is considered to be one of the major risk factors leading to cardiovascular-related diseases. Germinated brown rice (GBR) is a typical whole grain food. The lipid-lowering effect of GBR has received increasing attention, but its mechanism of action is not fully understood. The gut microbiota has been proposed as a novel target for the treatment of hyperlipidemia. The aim of this study was to investigate the effects of GBR on the gut microbiota and lipid metabolism in high-fat diet (HFD)-fed C57BL/6J mice. The effect of GBR on hyperlipidemia was evaluated by measuring blood lipid levels and by pathological examination. The gut microbiota was detected by 16S rRNA sequencing, and the protein and mRNA expression levels involved in cholesterol metabolism were detected by western blotting and RT-qPCR to find potential correlations. The results showed that GBR supplementation could effectively reduce the levels of TC, TG, LDL-C and HDL-C in the serum and alleviate the excessive accumulation of fat droplets caused by HFD. Moreover, GBR intervention improved HFD-fed gut microbiota disorder via increasing the diversity of the gut microbiota, reducing the Firmicutes/Bacteroidetes ratio, and improving gut barrier damage. In addition, GBR could inhibit endogenous cholesterol synthesis and promote cholesterol transport and excretion. These findings suggest that GBR may be a competitive candidate for the development of functional foods to prevent abnormal lipid metabolism.

Laparoscopic prostatectomy with complete urethral reconstruction for sexual active BPH patients.

OBJECTIVE: To describe our technique of transvesical laparoscopic simple prostatectomy (LSP) plus complete urethral reconstruction(CUR). MATERIAL AND METHODS: From May 2019 to May 2021, 28 BPH patients with prostate volumes > 80 ml and the requirement to preserve the ejaculatory function (EF) received LSP plus CUR. Baseline demographics, pathology data, perioperative and postoperative complications, and functional outcomes were assessed. Data were analyzed with the Wilcoxon test. RESULTS: The median prostate volume was 106 ml. All patients successfully underwent LSP with no intraoperative complications or conversions to open surgery. The median operative time was 146 min. A total of five Clavien-Dindo Grade1-2 postoperative complications were noted, including infection, prolonged urine leakage and cardiac arrhythmia. No patient reported postoperative urgent or stress urinary incontinence. Functional outcomes at one-year follow-up demonstrated significant improvement from baseline with median IPSS and Qmax (p both < 0.001). Compared with baseline, no significant difference was observed in IIEF and MSHQ-EjD-SF at 6 and 12 months postoperatively. CONCLUSIONS: Our data support transperitoneal-transvesical LSP plus CUR as a safe and effective surgical technique for treating BPH with large prostate adenoma, regardless of the volume of the median lobe, especially for patients requiring to preserve antegrade ejaculation.

Comparison of RLP and PCNL for large pelvis calculi with CKD.

OBJECTIVES: To compare the effect and safety of retroperitoneal laparoscopic pyelolithotomy (RLP) and percutaneous nephrolithotomy (PCNL) for large pelvis calculi with chronic kidney disease (CKD). MATERIAL AND METHODS: Between June 2017 and July 2021, 62 patients with CKD and large renal pelvis calculi (>4 cm2) were treated with RLP. Another 62 patients receiving PCNL served as controls. The perioperative parameters were compared. All patients were followed up for at least 6 months with the stone-free rate and the recovery of renal function evaluated. RESULTS: Significantly longer operation time (101.47 ± 9.25 vs 62.55 ± 7.54 min), less drop in hemoglobin level (0.90 ± 0.38 vs 2.13 ± 0.80 g/dl), staged operations (0% vs 12.9%), postoperative fever (3.23% vs 16.13%) and delayed bowel movement (3.23% vs 14.52), and shorter hospitalization time (3.90 ± 1.66 vs 4.72 ± 1.80 days) were observed in the RLP group (p < 0.05). The stone-free rates were 100% in the RLP group and 88.7% in the PCNL group at the 3-months follow-up (p < 0.05). The serum creatinine level was significantly lower in the RLP group at 24 h (2.81 ± 1.18 vs 3.00 ± 1.15 mg/dl) and 1 week (2.08 ± 1.13 vs 2.34 ± 1.01 mg/dl) postoperatively (p < 0.05). CONCLUSIONS: Although associated with a longer operation time, RLP is a safer and more efficient surgical option for CKD patients with large pelvic stones than PCNL.

Targeting gut-brain axis by dietary flavonoids ameliorate aging-related cognition decline: Evidences and mechanisms.

Aging-related cognitive impairment, mainly Alzheimer's disease (AD), has been widely studied. However, effective prevention and treatment methods are still lacking. In recent years, researchers have observed beneficial effects of plant-based supplements, such as flavonoids, on cognitive protection. This provides a new clue for the prevention of cognitive dysfunction. Studies have shown that dietary flavonoids have neuroprotective effects, but the mechanism is not clear. In this review, we systematically reviewed the research progress on the effects of dietary flavonoids on gut microbes and their metabolites, and concluded that flavonoids could improve cognitive function through the gut-brain axis. Flavonoids can be absorbed through the intestine, cross the blood-brain barrier, and enter the brain tissue. Flavonoids can inhibit the expression and secretion of inflammatory factors in brain tissue, reduce the damage caused by oxidative stress, clear neural damage proteins and inhibit neuronal apoptosis, thereby ameliorating age-related cognitive disorders. Future work will continue to explore the gut-brain axis and target genes regulated by flavonoids. In addition, clinical research and its mechanisms need to be further explored to provide solutions or advise for patients with cognitive impairment.

Pharmacokinetic study on the effect of ligustrazine-tangeretin co-administration on the pharmacokinetics of ligustrazine and its potential mechanism in rats.

Both ligustrazine and tangeretin are usually prescribed in the treatment of cardiovascular diseases, which makes their co-administration possible. The investigation of the interaction between ligustrazine and tangeretin is necessary for the clinical compatibility of their source herbs. This study aimed to investigate the interaction of ligustrazine and tangeretin during their co-administration. The pharmacokinetics of ligustrazine (15 mg/kg) was investigated in the presence of 50, 100, and 150 mg/kg tangeretin in rats with six of each. A single dose of ligustrazine was set as the control. The effect of tangeretin on the in vitro metabolic stability of ligustrazine was also investigated in rat liver microsomes. Tangeretin significantly reduced the system exposure of ligustrazine under all experimental concentrations. Specifically, tangeretin reduced the AUC (from 48.86 ± 12.57 to 41.02 ± 4.85 (50 mg/kg tangeretin), 31.47 ± 5.26 (100 mg/kg tangeretin), and 27.55 ± 9.60 (150 mg/kg) µg/mL × h), MRT (from 7.05 ± 0.26 to 6.33 ± 0.48, 5.53 ± 0.68, and 5.21 ± 1.31 h), Cmax (from 7.45 ± 0.44 to 6.03 ± 0.44, 5.24 ± 0.47, and 5.02 ± 0.56 µg/mL), and t1/2 (from 5.90 ± 1.27 to 4.84 ± 1.19, 3.48 ± 1.33, 3.09 ± 0.62 h) in rats. In vitro, tangeretin also reduced the metabolic stability of ligustrazine behaved as the decreased half-life and increased intrinsic clearance rate. Co-consumption of ligustrazine with tangeretin induced interactions, which shortens the system exposure of ligustrazine. This study provides theoretical guidance for the clinical prescription of ligustrazine- and tangeretin-containing herbs.

Degradation of PAHs in soil by activated persulfate system with activated carbon supported iron-based bimetal.

We developed a material of activated carbon (AC)-supported highly active iron-based bimetal (iron-copper bimetal/AC, Fe-Cu/AC) with high efficiency for polycyclic aromatic hydrocarbons (PAHs) degradation in soil by activating persulfate, benefiting from the synergistic effect that the characteristics of AC with porous carbon backbone, multiple active functional groups, high loading capacity and the characteristics of FeCu bimetal with high activity. The addition of Cu to the Fe-based/AC activator not only improved the dispersibility of Fe particles but also maintained the stability of the metal in the Fe-Cu/AC. The thermal activation (50 °C) promoted the degradation of PAHs by the Fe-Cu/AC-activated S2O82- system. Of the various systems tested, the Fe-Cu/AC-activated S2O82- system had the best degradation efficiency for 19 PAHs, with the overall efficiency following the order of Fe-Cu/AC + S2O82- > Fe-Cu + S2O82- > Fe-Cu/AC > S2O82-. The degradation mechanism of the Fe-Cu/AC-activated S2O82- system on soil PAHs showed that OH, OOH, and SO4- were the main active groups involved in the degradation of target PAHs. The target pollutants and their degradation products in the Fe-Cu/AC-activated S2O82- system indicated specific exposure pathways, providing a theoretical basis for the remediation of PAH-contaminated soil.

Current advances and challenges in CAR T-Cell therapy for solid tumors: tumor-associated antigens and the tumor microenvironment.

The past decade has witnessed ongoing progress in immune therapy to ameliorate human health. As an emerging technique, chimeric antigen receptor (CAR) T-cell therapy has the advantages of specific killing of cancer cells, a high remission rate of cancer-induced symptoms, rapid tumor eradication, and long-lasting tumor immunity, opening a new window for tumor treatment. However, challenges remain in CAR T-cell therapy for solid tumors due to target diversity, tumor heterogeneity, and the complex microenvironment. In this review, we have outlined the development of the CAR T-cell technique, summarized the current advances in tumor-associated antigens (TAAs), and highlighted the importance of tumor-specific antigens (TSAs) or neoantigens for solid tumors. We also addressed the challenge of the TAA binding domain in CARs to overcome off-tumor toxicity. Moreover, we illustrated the dominant tumor microenvironment (TME)-induced challenges and new strategies based on TME-associated antigens (TMAs) for solid tumor CAR T-cell therapy.

Circ_0091822 aggravates ox-LDL-induced endothelial cell injury through targeting the miR-661/RAB22A axis.

BACKGROUND: Endothelial dysfunction is considered to be an important factor in the pathogenesis of atherosclerosis. Circular RNAs (circRNAs) have been confirmed to participate in the development of atherosclerosis. Nevertheless, the role and mechanism of circ_0091822 in atherosclerosis have not been studied yet. METHODS: The expression of circ_0091822, miR-661 and RAB22A were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were estimated by enzyme-linked immunosorbent assay (ELISA). Cell viability was analyzed by Cell Counting Kit-8 (CCK-8) assay, cell proliferation was evaluated by EdU assay, and cell apoptosis was gauged by flow cytometry. Western blot was performed to assess the protein levels of Bax, Cleaved-caspase-3 and RAB22A. The interaction among miR-661 and circ_0091822 or RAB22A was verified by dual-luciferase reporter assayRESULTS:Ox-LDL enhanced the expression of circ_0091822 in HUVECs. It also constrained proliferation, promotes apoptosis and inflammation in HUVECs, and down-regulation of circ_0091822 attenuated these effects. Mechanically, circ_0091822 could serve as a sponge of miR-661, miR-661 interference rescued circ_0091822 inhibition-mediated effect on the biological functions in ox-LDL-induced HUVECs. Additionally, RAB22A was a target of miR-661, and its overexpression could partially overturn the negative regulation of miR-661 on ox-LDL-treated HUVECs injury. Importantly, circ_0091822 sponged miR-661 to positively regulate RAB22A expression. CONCLUSION: Circ_0091822 contributed to cell injury by targeting miR-661/RAB22A axis in ox-LDL-stimulated HUVECs.

Oryzanol Ameliorates DSS-Stimulated Gut Barrier Damage via Targeting the Gut Microbiota Accompanied by the TLR4/NF-κB/NLRP3 Cascade Response In Vivo.

Inflammatory bowel disease (IBD) is a global chronic disease with a long duration and repeated relapse. Currently, there is still a lack of effective approaches to prevent IBD. Food-derived oryzanol (ORY) possesses extensive biological activities, such as ameliorating bowel diseases, antioxidation, and antiobesity. However, the mechanism of ORY in preventing colitis remains unclear. The present research aims to explore the potential mechanism of ORY in dextran sulfate sodium (DSS)-stimulated colitis in a rat model. The results showed that the symptoms of colitis were significantly improved with the administration of ORY. Mechanismly, the expression levels of Zonula occludens-1 (ZO-1), Claudin-1, Occludin, MUC2, and TFF3 were elevated through ORY treatment, suggesting that oral ORY relieved the degree of gut barrier damage of colitis rats. Meanwhile, 16S sequencing results found that ORY supplementation increased the abundances of Alloprevotella, Roseburia, Treponema, Muribaculaceae, and Ruminococcus, which are associated with the synthesis of short-chain fatty acids (SCFAs). Moreover, GC-MS results confirmed that ORY supplementation reversed the DSS-induced reduction of acetic acid, butyric acid, and total acid. Further research indicated that ORY intervention downregulated the TLR4/NF-κB/NLRP3 pathway, which is closely linked to the expression of proinflammatory cytokines and colon injury. Taken together, ORY ameliorates DSS-stimulated gut barrier damage and inflammatory responses via the gut microbiota-TLR4/NF-κB/NLRP3 signaling axis.

Laminarin ameliorates alcohol-induced liver damage and its molecular mechanism in mice.

Alcoholic liver disease (ALD) has become a health issue globally. Laminarin, a low molecular weight marine-derived ß-glucan, has been identified with multiple biological activities. In this study, the ameliorative effect on ALD of laminarin isolated from brown algae was investigated. Phenotypic, pathological alterations and biochemical characteristics indicated that laminarin administration (100 mg/kg/day) significantly alleviated liver injury and improved liver function in the alcohol-induced mice. Gene chip results indicated that laminarin treatment caused 52 up-regulated and 13 down-regulated genes in the hepatic tissues of alcohol-induced damage mice, and most of these genes are associated with regulation of oxidative stress (such as CYP450/glutathione-dependent antioxidation), Wnt signaling pathway, retinol metabolism, and cAMP pathway based on GO and KEGG analysis. PPI network analysis indicated that the downstream target genes lied in the hub of the net. Our experiments also confirmed the changed expressions of some target genes. Taken together, these results suggest that laminarin can ameliorate alcohol-induced damage in mice and its molecular mechanism lies in modulating anti-oxidation pathway, WNT pathway, and cAMP pathway, which regulate the expressions of downstream target genes and alleviate alcohol-induced damage. Our study provides new clue to prevent alcohol-induced damage and will be benefit to develop functional foods. PRACTICAL APPLICATIONS: This study verified the positive effect on alcoholic liver disease (ALD) of laminarin, a water-soluble brown algae-derived ß-glucan, linked by ß-(1,3) glycosidic bonds with ß-(1,6) branches. Laminarin significantly alleviated liver injury and improved liver function of ALD mice. Moreover, transcriptomics and bioinformatics analysis further revealed the gene expression patterns, hub targets, and signalings including CYP450/glutathione, Wnt, retinol metabolism, cAMP pathways regulated by laminarin. This research is the first evidence for hepatoprotective effect of laminarin against ALD and its molecular mechanism, which will be advantage to develop functional foods or adjuvant therapy of ALD.

The nomograms for predicting overall and cancer-specific survival in elderly patients with early-stage lung cancer: A population-based study using SEER database.

Purpose: Lung cancer is the leading cause of death from cancer and the number of operable elderly lung cancer patients is increasing, with advanced age being associated with a poorer prognosis. However, there is no easy and comprehensive prognostic assessment method for these patients. Methods: Clinicopathological data of patients aged 65 years or older with TNM stage I-II lung cancer from 2004 to 2018 were downloaded from the SEER database. Patients from 2004 to 2015 were randomized into a training group (n = 16,457) and a validation group (n = 7,048). Data from 2016 to 2018 (n = 6,231) were used for external validation. Two nomogram prognostic models were created after independent prognostic factors connected to both overall survival (OS) and cancer-specific survival (CSS) in the training set by using univariate and multivariate Cox proportional hazards regression analysis. In turn, overall survival (OS) and cancer-specific survival (CSS) were predicted for patients at 1, 3, and 5 years. Based on the concordance index (C-index), calibration curves, area under the receiver operating characteristics (ROC) curve (AUC), the time-dependent area under the ROC curve, the validity, accuracy, discrimination, predictive ability, and clinical utility of the models were evaluated. Decision curve analysis (DCA) was used to assess the clinical value of the models. Results: A total of 29,736 patients were included. Univariate and multivariate analyses suggested that age, race, gender, marriage, disease grade, AJCC stage, T-stage, surgery, radiotherapy, chemotherapy, and tumor size were independent risk factors for patient prognosis. These 11 variables were included in nomogram to predict OS and CSS of patients. C-indexes of OS for the training, validation and external validation sets were 0.730 (95% CI, 0.709-0.751), 0.734 (95% CI, 0.722-0.746), and 0.750 (95% CI, 0.734-0.766), respectively. The AUC results for the training and validation sets indicated good accuracy for this nomogram. The calibration curves demonstrated a high degree of concordance between actual and anticipated values, and the DCA demonstrated that the nomograms had better clinical application than the traditional TNM staging approach. Conclusion: This study identified risk factors for survival in operable elderly lung cancer patients and established a new column line graph for predicting OS and CSS in these patients. The model has good clinical application and can be a good clinical decision-making tool for physicians and patients.

Predicting Mortality in Intensive Care Unit Patients With Heart Failure Using an Interpretable Machine Learning Model: Retrospective Cohort Study.

BACKGROUND: Heart failure (HF) is a common disease and a major public health problem. HF mortality prediction is critical for developing individualized prevention and treatment plans. However, due to their lack of interpretability, most HF mortality prediction models have not yet reached clinical practice. OBJECTIVE: We aimed to develop an interpretable model to predict the mortality risk for patients with HF in intensive care units (ICUs) and used the SHapley Additive exPlanation (SHAP) method to explain the extreme gradient boosting (XGBoost) model and explore prognostic factors for HF. METHODS: In this retrospective cohort study, we achieved model development and performance comparison on the eICU Collaborative Research Database (eICU-CRD). We extracted data during the first 24 hours of each ICU admission, and the data set was randomly divided, with 70% used for model training and 30% used for model validation. The prediction performance of the XGBoost model was compared with three other machine learning models by the area under the curve. We used the SHAP method to explain the XGBoost model. RESULTS: A total of 2798 eligible patients with HF were included in the final cohort for this study. The observed in-hospital mortality of patients with HF was 9.97%. Comparatively, the XGBoost model had the highest predictive performance among four models with an area under the curve (AUC) of 0.824 (95% CI 0.7766-0.8708), whereas support vector machine had the poorest generalization ability (AUC=0.701, 95% CI 0.6433-0.7582). The decision curve showed that the net benefit of the XGBoost model surpassed those of other machine learning models at 10%~28% threshold probabilities. The SHAP method reveals the top 20 predictors of HF according to the importance ranking, and the average of the blood urea nitrogen was recognized as the most important predictor variable. CONCLUSIONS: The interpretable predictive model helps physicians more accurately predict the mortality risk in ICU patients with HF, and therefore, provides better treatment plans and optimal resource allocation for their patients. In addition, the interpretable framework can increase the transparency of the model and facilitate understanding the reliability of the predictive model for the physicians.

Downregulation of interleukin-1 beta via Jmjd3 inhibition improves post-myocardial infarction depression.

Background: Patients with myocardial infarction (MI) comorbid with the depressive disorder may have increased serum cytokine concentrations, notably, of interleukin-1 beta (IL-1ß). The histone H3 lysine-27 (H3K27) demethylase Jmjd3 is crucial in cytokine regulation, and administering an H3K27 demethylase-selective inhibitor (GSK J4) might ameliorate inflammatory symptoms. We hypothesized that Jmjd3 might regulate IL-1ß concentrations, thus affecting the development of post-MI depression (PMD). In this study, a mouse model was created to examine the connection between IL-1ß and PMD and determine the regulatory function of cytokine in controlling inflammation and depressive symptoms. Methods: MI was induced in 30 5-week-old male C57BL/6N mice via a left coronary ligation, and MI onset was confirmed by electrocardiogram (ECG). After treatment with dimethylsulfoxide (DMSO) or GSK J4 for 14 days, the mice were subjected to tail-suspension tests (TSTs) and forced swimming tests (FSTs) before being sacrificed for tissue harvest. Results: In the TSTs, the GSK J4-treated MI mice displayed a significantly shorter immobility time than did the DMSO-treated MI mice (P<0.001). In the FSTs, the DMSO-treated MI mice showed a significantly longer immobility time than did the DMSO-treated sham-operated mice (P<0.001). The GSK J4-treated MI mice had a significantly reduced immobility time compared to the DMSO-treated MI mice (P<0.001). IL-1ß expression in the myocardium, hippocampus, prefrontal cortex (PFC), and hypothalamus increased after MI onset (P=0.003, 0.015, 0.0003, and 0.013, respectively) but decreased after treatment with GSK J4 (P<0.001, P=0.005, P<0.001, P=0.018, respectively). In the myocardium and hypothalamus, Jmjd3 expression levels were lower in mice that received GSK J4 treatment than in those that received DMSO treatment (P<0.05). Conclusions: GSK J4 inhibited the cardiac expression of IL-1ß and Jmjd3, and alleviated PMD in MI mice. Therefore, IL-1ß and Jmjd3 may be critical in the pathogenesis of PMD, and Jmjd3 may potentially serve as a target for PMD treatment.

Octacosanol Modifies Obesity, Expression Profile and Inflammation Response of Hepatic Tissues in High-Fat Diet Mice.

The incidence of obesity has increased significantly on account of the alterations of living habits, especially changes in eating habits. In this study, we investigated the effect of octacosanol on lipid lowering and its molecular mechanism. High-fat diet (HFD)-induced obesity mouse model was used in the study. Thirty C57BL/6J mice were divided into control, HFD, and HFD+Oct groups randomly, and every group included ten mice. The mice of HFD+Oct group were intragastrically administrated 100 mg/kg/day of octacosanol. After 10 weeks for treatment, our results indicated that octacosanol supplementation decreased the body, liver, and adipose tissues weight of HFD mice; levels of TC, TG, and LDL-c were reduced in the plasma of HFD mice; and level of HDL-c were increased. H&E staining indicated that octacosanol supplementation reduces the size of fat droplets of hepatic tissues and adipose cells comparing with the HFD group. Gene chip analysis found that octacosanol regulated 72 genes involved in lipid metabolism in the tissues of liver comparing to the HFD group. IPA pathway network analysis indicated that PPAR and AMPK may play a pivotal role in the lipid-lowering function of octacosanol. Real-time quantitative PCR and Western blot showed that the octacosanol supplementation caused change of expression levels of AMPK, PPARs, FASN, ACC, SREBP-1c, and SIRT1, which were closely related to lipid metabolism. Taken together, our results suggest that octacosanol supplementation exerts a lipid-decreasing effect in the HFD-fed mice through modulating the lipid metabolism-related signal pathway.

The Impact of Chronic Illness on the Patient Experience: Results From a Cross-Sectional Comparative Study in a Comprehensive Tertiary Hospital in China.

OBJECTIVE: Improving the satisfaction and medical experience of patients is a basic goal of the comprehensive reform of public hospitals in China. This study aimed to investigate the patient experience and its influencing factors, and to compare medical experiences between patients with and without chronic disease, with a view to providing suggestions for improving the quality of public hospitals in China. METHODS: A cross-sectional comparative study involving 102 patients discharged from Taizhou Hospital of Zhejiang Province, a tertiary public hospital in China, was conducted. The patients were invited to participate in a survey comprising the Picker Patient Experience Questionnaire (PPE-15), and an overall satisfaction evaluation (on a scale of 1-10). The patients were divided into two groups according to whether or not they had a chronic disease, and the medical experience and overall satisfaction of the groups were compared. Descriptive statistics (frequency, median, mean), chi-square analysis, and Mann-Whitney U tests were used to analyze the data. RESULTS: No statistical significance was found in overall satisfaction between patients with and without chronic diseases, but there were differences in the patient experience score. Chronic illness had negative impacts on the experience of care coordination for patients and respect for patient preferences. Of the seven dimensions of the PPE-15, the scores for emotional support and respect for patient preferences were the lowest in both groups, and the item "want to be more involved in decisions made about care and treatment" scored the lowest among all items. CONCLUSIONS: Hospital managers and staff members should pay more attention to the emotional support and preferences of patients. For patients with chronic diseases, the standardization of medical care and patient participation in the medical process should be strengthened. Hospitals should also subdivide patient groups, ascertain the demands and expectations of patients, and carry out targeted evaluation and intervention measures.

Oryzanol Attenuates High Fat and Cholesterol Diet-Induced Hyperlipidemia by Regulating the Gut Microbiome and Amino Acid Metabolism.

Hyperlipidemia is intricately associated with the dysregulation of gut microbiota and host metabolomes. This study explored the antihyperlipidemic function of oryzanol and investigated whether the function of oryzanol affected the gut microbiome and its related metabolites. Hamsters were fed a standard diet (Control) and a high fat and cholesterol (HFCD) diet with or without oryzanol, separately. Our results showed that oryzanol significantly decreased HFCD-induced fat accumulation, serum total cholesterol, low-density lipoprotein cholesterol (LDL-c), LDL-c/HDL-c ratio, triglyceride, and liver steatohepatitis, attenuated HFCD-induced gut microbiota alterations, and altered amino acid concentrations in feces and the liver. We investigated the role of the gut microbiota in the observed beneficial effects; the protective effects of oryzanol were partly diminished by suppressing the gut bacteria of hamsters after using antibiotics. A fecal microbiota transplantation experiment was carried out by transplanting the feces from HFCD group hamsters or hamsters given oryzanol supplementation (as a donor hamster). Our results showed that administering the fecal liquid from oryzanol-treated hamsters attenuated HFCD-induced hyperlipidemia, significantly decreased the abundance of norank_f__Erysipelotrichaceae, norank_f__Eubacteriaceae, and norank_f__Oscillospiraceae and the concentration of tyrosine. These outcomes are significantly positively correlated with serum lipid concentration. This study illustrated that gut microbiota is the target of oryzanol in the antihyperlipidemic effect.