Phillyrin inhibits oxidative stress and neutrophil extracellular trap formation through the KEAP1/NRF2 pathway in gouty arthritis.

Gouty arthritis (GA) is an inflammatory disorder characterized by deposition of monosodium urate (MSU) crystal in joints. Phillyrin, a natural compound with anti-inflammatory properties, shows promise in mitigating inflammatory responses. This study investigates the therapeutic potential of phillyrin in GA and explores its mechanisms of action. GA was induced in mice via intraarticular MSU injection, and joint inflammation, inflammatory cell infiltration, and their level in serum/tissue were assessed. Key proteins in the NF-κB and NLRP3 pathways were examined using western blot analysis. The impact of phillyrin on oxidative stress, neutrophil extracellular trap (NET) formation, and neutrophil accumulation was evaluated by measuring CD11b + Ly6G + cells, MPO, CitH3, extracellular DNA ratio, and oxidative stress markers. In vitro studies assessed the effects of phillyrin on oxidative stress, cell viability, cytokine production, and NET formation in MSU-treated neutrophils. The KEAP1/NRF2 pathway's role was analyzed using ML385, an NRF2 inhibitor. Phillyrin significantly reversed MSU-induced ankle swelling and inflammatory cell infiltration in joint tissues. It suppressed pro-inflammatory cytokines and proteins in the NF-κB and NLRP3 pathways. Phillyrin reduced neutrophil infiltration, evidenced by lower MPO activity and NET formation, marked by reduced CitH3 expression. In vitro, phillyrin inhibited inflammatory marker expression and NET formation without affecting cell viability. It also restored antioxidant enzyme levels and reduced ROS production, regulating the KEAP1/NRF2 pathway, enhancing NRF2 expression and stability. These effects were reversed by NRF2 inhibition with ML385. Phillyrin alleviates GA by reducing joint inflammation, inhibiting NET formation, and suppressing oxidative stress through NRF2 modulation.

An MRI-based radiomics nomogram to predict progression-free survival in patients with endometrial cancer.

Aim: This study aimed to explore the importance of an MRI-based radiomics nomogram in predicting the progression-free survival (PFS) of endometrial cancer.Methods: Based on clinicopathological and radiomic characteristics, we established three models (clinical, radiomics and combined model) and developed a nomogram for the combined model. The Kaplan-Meier method was utilized to evaluate the association between nomogram-based risk scores and PFS.Results: The nomogram had a strong predictive ability in calculating PFS with areas under the curve (ROC) of 0.905 and 0.901 at 1 and 3 years, respectively. The high-risk groups identified by the nomogram-based scores had shorter PFS compared with the low-risk groups.Conclusion: The radiomics nomogram has the potential to serve as a noninvasive imaging biomarker for predicting individual PFS of endometrial cancer.

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Tetrandrine alleviates inflammation and promotes macrophage M2 polarization in gouty arthritis by NF-κB-mediated Lcp1.

Gouty arthritis (GA) is an inflammatory disease caused by the deposition of monosodium urate (MSU) crystals into joints. Tetrandrine (TET) is a bisbenzylisoquinoline alkaloid extracted from the root of Stephania tetrandra and can exert an anti-inflammatory function in different diseases. Nevertheless, the specific function of TET in GA remains unclear. We established the GA mouse model by MSU injection into joints of mice. Paw volume and gait score were detected for measuring the degree of joint swelling and the situation of joint dysfunction. Western blot were utilized to test the alterations of M1-related factors (IL-6, IL-1ß, TNF-α, IL-12, and iNOS) and M2-related factors (Mgl1, Mgl2, Pgc1-ß, Arg-1, and IL-10). The activity of NF-κB p65 in tissues was determined. The interaction of NF-κB p65 and Lcp1 was measured by ChIP and luciferase reporter assay. Lcp1 KO mice were utilized to detect the effect of Lcp1 depletion on GA process. TET treatment markedly suppressed MSU-induced joint swelling, joint dysfunction, and joint injury in GA mice. TET can also reduce inflammatory reactions in MUS-induced mice. Furthermore, we proved that TET facilitated M2 macrophage polarization and inhibited M1 macrophage polarization in GA mice. In addition, TET was found to inhibit NF-κB activity and NF-κB-mediated Lcp1 expression. Lcp1 knockdown can improve joint injury and promote M2 macrophage polarization in GA mice, while this effect was further enhanced by TET. TET alleviates inflammation and facilitates macrophage M2 polarization in GA by NF-κB-mediated Lcp1.

Icariin has the potential to induce the differentiation of bone marrow mesenchymal stem cells into brown fat cells via PDE5A inhibition.

Background: Bone marrow mesenchymal stem cells (BMMSCs) possess the ability of adipogenic differentiation. Icariin (ICA) is a prenylated flavonol glycoside with diverse pharmacological activities and has been reported to promote osteogenic differentiation of BMMSCs. Nevertheless, the effects of ICA on BMMSC adipogenic differentiation into brown fat cells are still unclear. This study aimed to explore the effects and mechanistic basis of ICA on the differentiation of BMMSCs into brown fat cells. Methods: Oil Red-O staining assay was applied to detect the adipogenic differentiation of BMMSCs after induction. RT-qPCR and Western blot were conducted to detect the expression of lipogenic markers PPARγ and FABP4 as well as the brown fat biomarkers BMP7, PGC-1α, and UCP1 in BMMSCs. Moreover, phosphodiesterase-5A (PDE5A) expression in BMMSCs treated with ICA was measured by RT-qPCR and Western blot. Results: ICA promoted the adipogenic differentiation of BMMSCs and increased the expression levels of lipogenic markers PPARγ and FABP4 and the brown fat biomarkers BMP7, PGC-1α, and UCP1 during the adipogenic differentiation of BMMSCs. Furthermore, PDE5A was identified as a target of ICA, and its expression was reduced by ICA treatment. Moreover, PDE5A inhibition enhanced BMP7, PGC-1α, and UCP1 levels in BMMSCs. Additionally, overexpression of PDE5A notably reversed the effects of ICA in the differentiation of BMMSCs into brown fat cells. Conclusion: ICA induces the differentiation of BMMSCs into brown fat cells via PDE5A inhibition, highlighting the therapeutic value of ICA for treating obesity-related diseases.

Cultural factors affecting Chinese migrants' perceptions and responses to cancer pain and its pharmacological management: A convergent mixed-method study.

INTRODUCTION: Studies identified barriers of pain reporting and use of analgesics impeding Chinese cancer patients to achieve optimal pain relief. No research has yet explored these issues in Chinese migrants, where cultural differences may exacerbate the barriers. OBJECTIVES: To explore cultural factors influencing Chinese migrants' perspectives to cancer pain and its pharmacological management. METHOD: Informed by Leininger's Cultural Care Theory, focus groups and a short version of Barrier Questionnaire-Taiwan (S-BQT) were conducted in Mandarin or Cantonese, with 24 Chinese migrants receiving ambulatory cancer and/or palliative care services in Sydney, Australia. Integrated thematic analysis, descriptive statistics, and meta-inference were adopted for data analysis and integration. RESULTS: Participants suffered uncontrolled cancer pain negatively affecting their physical and psychosocial well-being. Most experienced moderate to severe pain, but only a third used opioids. Most adopted non-pharmacological approaches and half used Traditional Chinese Medicine. Participants scored a mean S-BQT of 3.28 (standard deviation ± 0.89). Three themes and seven sub-themes contributed to higher barriers of pharmacological pain management: (1) Philosophical health beliefs (cancer pain are self-provoked and body can self-heal); (2) Cultural values and beliefs (cancer pain is inevitable, and Chinese people express pain differently to local people); and (3) Conflicting views on the use of opioids (culture-related negative medication beliefs, Western biomedical model-related opioid fears, and opioids extend life for people with terminal cancer pain). CONCLUSIONS: Chinese migrants' responses to cancer pain and attitudes towards opioids are complex. Culturally congruent strategies are needed to overcome culture-related barriers and improve quality of cancer pain care in this population.

MicroRNA-486-5p suppresses inflammatory response by targeting FOXO1 in MSU-treated macrophages.

Gouty arthritis (GA) is mainly caused by the precipitation of monosodium urate (MSU) crystals in the joint. Recently, different regulatory roles of microRNAs (miRNAs) in arthritis have been widely verified. Nevertheless, the specific function of microRNA-486-5p (miR-486-5p) in GA is still unclear. GA cell models in vitro were established by the treatment of 250 µg/mL MSU crystals into THP-1 cells or J774A.1 cells. Then, the accumulation of tumor necrosis factor (TNF)-α, interleukin (IL)-8, and IL-ß was estimated by ELISA. The mRNA levels of TNF-α, IL-8, and IL-ß were measured through RT-qPCR. The protein level of forkhead box protein O1 (FOXO1) was tested via western blot. Furthermore, the interplay of miR-486-5p and FOXO1 was evaluated via the luciferase reporter assay. In this study, MSU treatment successfully stimulated the inflammatory response in macrophage cells. MiR-486-5p downregulation was observed in THP-1 and J774A.1 cells treated with MSU, and its upregulation markedly decreased the concentration and mRNA levels of TNF-α, IL-8, and IL-ß. Furthermore, FOXO1 was demonstrated to be negatively modulated by miR-486-5p. The rescue assay indicated that overexpressing FOXO1 reversed the effects of overexpressing miR-486-5p on inflammatory cytokines. Overall, this study proves that miR-486-5p inhibits GA inflammatory response via modulating FOXO1.

MicroRNA-142-3p facilitates inflammatory response by targeting ZEB2 and activating NF-κB signaling in gouty arthritis.

Gouty arthritis (GA) is caused by monosodium urate (MSU) crystal accumulation in the joints. MSU-mediated inflammation is an important inducing factor in gouty arthritis (GA). Recent studies have demonstrated that microRNAs can influence GA progression. Herein, the role and mechanism of miRNA-142-3p in GA were explored. To establish the in vitro and in vivo GA models, MSU was used to induce inflammatory response in human monocyte cell line THP-1 and male C57BL/6 mice. Protein levels, gene expression and proinflammatory cytokine secretion were respectively tested by Western blotting, RT-qPCR, and enzyme-linked immunosorbent assay (ELISA). Pathological changes in sagittal sections of ankle tissues were exhibited by hematoxylin-eosin (HE) staining. Binding relationship between miRNA-142-3p and zinc finger E-box binding homeobox 2 (ZEB2) was predicted and confirmed by bioinformatics analysis and luciferase reporter assay. In this study, MSU induced inflammatory response and upregulated miRNA-142-3p in THP-1 cells. Functionally, miRNA-142-3p knockdown inhibited inflammatory response in MSU-stimulated THP-1 cells and alleviated pathological symptoms of GA mice. Mechanically, miRNA-142-3p targeted ZEB2 in THP-1 cells. ZEB2 expression was elevated in MSU-administrated THP-1 cells and GA mice. ZEB2 downregulation reserved the inhibitory effect of miRNA-142-3p deficiency on inflammatory response in MSU-treated THP-1 cells. In addition, miRNA-142-3p activated NF-κB signaling by binding with ZEB2 in THP-1 cells upon MSU stimulation. Overall, miRNA-142-3p facilitates inflammatory response by targeting ZEB2 and activating NF-κB signaling in GA.

Long noncoding RNA SNHG8 accelerates acute gouty arthritis development by upregulating AP3D1 in mice.

Gout can affect the quality of life of patients due to monosodium urate monohydrate (MSU) crystals. Numerous studies have proposed that long noncoding RNAs (lncRNAs) regulate gout. We aimed to reveal the function of lncRNA small nucleolar RNA host gene 8 (SNHG8) in acute gouty arthritis (GA). A GA mouse model was established by injection of MSU into footpads. The levels of SNHG8, miR-542-3p and adaptor-related protein complex 3 subunit delta 1 (AP3D1) in footpads were detected via polymerase chain reaction analysis. Hematoxylin-eosin staining revealed the paw swelling in mice. Enzyme-linked immunosorbent assay and western blot analysis were applied to determine the concentrations of proinflammatory cytokines. SNHG8 expression was identified to be upregulated after MSU treatment. Ablation of SNHG8 decreased the MSU-induced enhancement of paw swelling and foot thickness. In addition, SNHG8 depletion decreased the protein levels of proinflammatory factors in GA mice. Mechanically, SNHG8 was verified to be a sponge of miR-542-3p, and miR-542-3p targeted AP3D1 3' untranslated region. SNHG8 competitively bound with miR-542-3p to upregulate AP3D1 expression. Finally, results of rescue assays illustrated that AP3D1 upregulation offset the SNHG8-mediated inhibition on paw swelling and protein levels of proinflammatory factors in GA mice. In conclusion, SNHG8 accelerates acute GA development by upregulating AP3D1 in an miR-542-3p-dependent way in mice, providing an effective therapeutic approach to treat acute GA.

Evaluation of Feature Selection Methods for Mammographic Breast Cancer Diagnosis in a Unified Framework.

Over recent years, feature selection (FS) has gained more attention in intelligent diagnosis. This study is aimed at evaluating FS methods in a unified framework for mammographic breast cancer diagnosis. After FS methods generated rank lists according to feature importance, the framework added features incrementally as the input of random forest which performed as the classifier for breast lesion classification. In this study, 10 FS methods were evaluated and the digital database for screening mammography (1104 benign and 980 malignant lesions) was analyzed. The classification performance was quantified with the area under the curve (AUC), and accuracy, sensitivity, and specificity were also considered. Experimental results suggested that both infinite latent FS method (AUC, 0.866 ± 0.028) and RELIEFF (AUC, 0.855 ± 0.020) achieved good prediction (AUC ≥ 0.85) when 6 features were used, followed by correlation-based FS method (AUC, 0.867 ± 0.023) using 7 features and WILCOXON (AUC, 0.887 ± 0.019) using 8 features. The reliability of the diagnosis models was also verified, indicating that correlation-based FS method was generally superior over other methods. Identification of discriminative features among high-throughput ones remains an unavoidable challenge in intelligent diagnosis, and extra efforts should be made toward accurate and efficient feature selection.

[Clinical observation of soft tissue wire rivets in the treatment of large patellar cartilage fracture].

OBJECTIVE: To explore the clinical curative effect of soft tissue wire rivet for the treatment of fracture of patella cartilage. METHODS: A retrospective study was conducted in 25 patients(25 knees) from June 2015 to February 2017 in patients with patellar cartilage fractures. Among them, 19 were male, 6 were female, 11 were left knee, 14 were right knee. The accident occurred in 2 cases, 23 cases of sprained athletes; the average age was(25.12±6.02) years old, the average weight was (62.48±7.91) kg, and the average body mass index was(23.25±1.51) kg/m². The average time from injury to admission was (1.96±1.51) d. The clinical manifestations were swelling of knee joint, positive floating patella sign, severe pain, occasional joint strangulation, limited flexion and extension, obvious tenderness of lateral patella, positive patellar extrapolation test and positive extrapolation fear test. X-ray and CT examination were performed before operation. X-ray showed the continuity of patellar bone and a loose body in the joint cavity. CT and 3D reconstruction showed patellar cartilage and facial defects. All 25 patients were fixed with soft tissue wire rivet. The clinical efficacy included preoperative Lysholm score and Insall evaluation. RESULTS: All the patients were followed up, and the duration ranged from 3 to 15 months, with an average of(9.72±4.07) months. The preoperative Lysholm score was 60.32±5.08, and the final follow-up was 88.24±4.37. The postoperative score was better than that before operation(t=-22.926, P<0.05). According to Insall criteria, 21 cases were excellent, 4 cases were good, no fracture fragments were found and knee joint adhesion was found. Six weeks after operation, X-ray and CT showed that the fracture was well positioned, the cartilage surface was smooth without obvious steps, and the patella was in good shape. MRI showed the smooth articular surface of patellar cartilage at the 6th month after operation. CONCLUSIONS: Soft tissue wire rivet for the treatment of massive patellar cartilage fracture has the advantages of simple operation, rapid postoperative recovery, no need for secondary operation pain, fewer complications, and definite effect, which is worthy of clinical promotion.

Cancer pain management needs and perspectives of patients from Chinese backgrounds: a systematic review of the Chinese and English literature.

OBJECTIVE: More than half of all cancer patients experience unrelieved pain. Culture can significantly affect patients' cancer pain-related beliefs and behaviors. Little is known about cultural impact on Chinese cancer patients' pain management. The objective of this review was to describe pain management experiences of cancer patients from Chinese backgrounds and to identify barriers affecting their pain management. METHOD: A systematic review was conducted adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were included if they reported pain management experiences of adult cancer patients from Chinese backgrounds. Five databases were searched for peer-reviewed articles published in English or Chinese journals between1990 and 2015. The quality of included studies was assessed using Joanna Briggs Institution's appraisal tools. RESULTS: Of 3,904 identified records, 23 articles met criteria and provided primary data from 6,110 patients. Suboptimal analgesic use, delays in receiving treatment, reluctance to report pain, and/or poor adherence to prescribed analgesics contributed to the patients' inadequate pain control. Patient-related barriers included fatalism, desire to be good, low pain control belief, pain endurance beliefs, and negative effect beliefs. Patients and family shared barriers about fear of addiction and concerns on analgesic side effects and disease progression. Health professional-related barriers were poor communication, ineffective management of pain, and analgesic side effects. Healthcare system-related barriers included limited access to analgesics and/or after hour pain services and lack of health insurance.Significance of resultsChinese cancer patients' misconceptions regarding pain and analgesics may present as the main barriers to optimal pain relief. Findings of this review may inform health interventions to improve cancer pain management outcomes for patients from Chinese backgrounds. Future studies on patients' nonpharmacology intervention-related experiences are required to inform multidisciplinary and biopsychosocial approaches for culturally appropriate pain management.

Effects of high-intensity interval versus mild-intensity endurance training on metabolic phenotype and corticosterone response in rats fed a high-fat or control diet.

The aim of the present study was to compare the effects of high-intensity interval training (HI) to mild-intensity endurance training (ME), combined with a high-fat diet (HFD) or control diet (CD) on metabolic phenotype and corticosterone levels in rats. Fifty-three rats were randomized to 6 groups according to diet and training regimen as follows: CD and sedentary (CS, n = 11), CD and ME (CME, n = 8), CD and HI (CHI, n = 8), HFD and sedentary (HS, n = 10), HFD and ME (HME, n = 8), and HFD and HI (HHI, n = 8). All exercise groups were trained for 10 weeks and had matched running distances. Dietary intake, body composition, blood metabolites, and corticosterone levels were measured. Histological lipid droplets were observed in the livers. The HFD led to hyperglycemia, hyperlipidemia and higher body fat (all, P < 0.01, η2 > 0.06), as well as higher corticosterone levels (P < 0.01, η2 = 0.09) compared with the CD groups. Exercise training improved fat weight, glucose, and lipid profiles, and reduced corticosterone levels (P < 0.01, η2 = 0.123). Furthermore, body and fat weight, serum glucose and triglycerides, lipid content in the liver, and corticosterone levels (P < 0.05) were lower with HI training compared to ME training. Reductions in HFD-induced body weight gain, blood glucose and lipid profiles, and corticosterone levels, as well as improvements in QUICKI were better with HHI compared to HME. Correlation analyses revealed that corticosterone levels were significantly associated with phenotype variables (P < 0.01). Corticosterone level was inversely correlated with QUICKI (r = -0.38, P < 0.01). Altogether, these results indicate that HFD may elicit an exacerbated basal serum corticosterone level and thus producing a metabolic imbalance. Compared with ME training, HI training contributes to greater improvements in metabolic and corticosterone responses, leading to a greater reduction in susceptibility to HFD-induced disorders.

Multislice Spiral Perfusion Computed Tomography to Assess Pancreatic Vascularity in Mild Acute Pancreatitis.

OBJECTIVE: This study aims to use perfusion computed tomography to compare pancreatic perfusion in mild acute pancreatitis (MAP) versus normal pancreas. METHODS: This observational study included 39 patients with MAP and 18 patients with normal pancreatic function. Perfusion computed tomography parameters, including blood flow (BF), blood volume (BV), mean transit time, and permeability surface area product, were compared. RESULTS: Both serum and urinary amylase levels were significantly higher in patients with MAP than in controls (all Ps < 0.05). Patients with MAP showed significantly lower BF and BV and higher mean transit time and permeability surface area product than the controls (all Ps < 0.05). Correlation analysis on the 39 patients with MAP revealed negative coefficients between serum amylase level and BF and BV values. CONCLUSIONS: Pancreatic perfusion seems to be poorer, and pancreatic vascular leakage may increase in MAP compared with normally functioned pancreas.

Effect of different exercise protocols on metabolic profiles and fatty acid metabolism in skeletal muscle in high-fat diet-fed rats.

OBJECTIVE: To evaluate the efficacy of mild-intensity endurance, high-intensity interval, and concurrent exercise on preventing high-fat diet-induced obesity. METHODS: Male rats were divided into five groups, control diet/sedentary group, high-fat diet/sedentary, high-fat diet/endurance exercise, high-fat diet/interval exercise (HI), and high-fat diet/concurrent exercise. All exercise groups were made to exercise for 10 weeks, with matched running distances. Body weight, fat content, blood metabolites, quantitative insulin sensitivity check index (QUICKI), and adipocyte and liver lipid droplet size were assessed, and the expression of fatty acid metabolism-related genes was quantified. RESULTS: All exercise protocols reduced body weight, adiposity, serum triglycerides, and fasting glucose and also improved QUICKI to some extent. However, only HI prevented obesity and its associated pathologies completely. The expression of stearoyl-coenzyme A desaturase-1 was elevated in all rats fed a high-fat diet whereas carnitine palmitoyltransferase 1 (CPT1) expression was increased with exercise. Rev-erbα expression was elevated only in the HI group, which also had the highest level of CPT1 expression. CONCLUSIONS: The HI-induced increase in Rev-erbα and CPT1 expression was associated with the complete prevention of diet-induced obesity. Moreover, the increased caloric expenditure achieved with this protocol was preferential over other exercise regimens, and might be used to improve lipid metabolism.

Phase shift selection for two-step generalized phase-shifting interferometry.

A phase shift selection method is proposed to design algorithms immune against phase shift errors in two-step generalized phase-shifting interferometry. A general formula for wavefront reconstruction error is derived, and its specific expressions for two common errors are also given. Calculation results suggest that the proper range of phase shift for general application is about from 0.5 to 2.0 rad for both the fixed and linear phase shift errors. Computer simulations have demonstrated the effectiveness of this phase shift selection method by decreasing the wave reconstruction errors to one-fifth.