Major depressive disorder (MDD) is a highly disabling psychiatric illness characterized by persistent low mood and psychomotor retardation, often leading to cognitive impairment or even suicidality. As the pathogenesis remains poorly understood, the currently available treatment regimens are mostly symptomatic therapies with little satisfactory curative effect. The emerging paradigm of gut-brain axis has highlighted gut dysbiosis as a key etiological factor to elicit neuro-inflammation and jeopardize the central nervous system homeostasis. In this study, we evaluated the ameliorating effects of flaxseed lignans on the gut microbiome to regain the gut micro-environmental functionality and alleviate MDD. The lignans significantly mitigated the severity of disease and markedly altered the gut microbiota structure in the participants. In the MDD mouse model, the lignans reversed the experimental depression-like behaviors, repaired neural and gut damage and restored barrier integrity. Of great significance, the lignans elevated the levels of 5-hydroxytryptamine (5-HT), brain-derived neurotrophic factor (BDNF) and γ-aminobutyric acid (GABA), and markedly attenuated microglial and systemic inflammation. Mechanistically, the lignans inhibited the IL-17/AP-1/NF-κB axis through direct interaction with the Fos protein. In the BV-2 cells, the lignan enterolactone reduced levels of nitric oxide and pro-inflammatory cytokines, further validating the anti-inflammatory mechanism of the lignans. Together, these findings demonstrate that lignans exert potent antidepressant effects by modulating the gut-brain axis and resolving neuro-inflammation, providing useful information for the development of novel therapeutic strategies for MDD prevention and treatment.

This study aimed to evaluate the clinical predictive value of combining N-terminal serum osteocalcin (N-MID) with thyroid transcription factor-1 (TTF-1) for bone metastasis in lung cancer. This retrospective analysis included 147 lung cancer patients admitted to the hospital between February 2020 and October 2024. Patients were divided into a bone metastasis group (n=83) and a non-bone metastasis group (n=64) based on the presence of bone metastases. Baseline clinical data and laboratory parameters, including TTF-1, N-MID, tumor abnormal protein (TAP), parathyroid hormone (PTH), vascular endothelial growth factor (VEGF), total N-terminal propeptide of type I collagen (tPINP), and β-C-terminal telopeptide of type I collagen (β-CTX) were collected. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for bone metastasis. Model performance was evaluated using receiver operating characteristic (ROC) curves, integrated discrimination improvement (IDI), category-based net reclassification improvement (cNRI), the Hosmer-Lemeshow goodness-of-fit test, and decision curve analysis (DCA). Age-stratified analysis and external validation were further conducted to ensure the generalizability of study. Univariate analysis showed that TTF-1 positivity rate and the levels of TAP, PTH, VEGF, tPINP, β-CTX, and N-MID were significantly higher in the bone metastasis group than in the non-bone metastasis group (all P<0.05). Multivariate logistic regression confirmed that TTF-1 (OR=2.217, 95% CI: 1.329-3.698, P<0.001) and N-MID (OR=2.519, 95% CI: 1.404-4.518, P<0.001) were independent risk factors for bone metastasis in lung cancer. After adding TTF-1 and N-MID to a baseline model that included PTH, VEGF, tPINP, and β-CTX, the area under the curve (AUC) increased from 0.752 to 0.837, with an IDI of 0.079 and a cNRI of 0.609 (both P<0.001). The Hosmer-Lemeshow test indicated good model fit, and external validation demonstrated good concordance between predicted probabilities and observed outcomes. Age-stratified analysis revealed that in elderly populations (70-79 years and 80-89 years), the combined detection of TTF-1 and N-MID yielded significantly higher AUC than either marker alone. Decision curve analysis confirmed that the combined detection provided a higher net benefit within clinically reasonable threshold ranges. In conclusion, TTF-1 and N-MID are independent risk factors for bone metastasis in lung cancer, and their combination significantly enhances the diagnostic performance of the predictive model, with particularly notable clinical value in elderly patients. These findings provide evidence-based references for early identification of bone metastasis and individualized clinical intervention in lung cancer.

PURPOSE:Compared with long-term dual antiplatelet therapy (DAPT, aspirin with clopidogrel or ticagrelor), short-term DAPT followed by single antiplatelet therapy (SAPT, clopidogrel or ticagrelor) has demonstrated superiority in reducing bleeding risk while maintaining non-inferior in cardiovascular benefits in coronary heart disease (CHD) after successful percutaneous coronary intervention (PCI). However, no prospective study has explored the benefits of this short-term regimen on patients with chronic total occlusion (CTO) undergoing PCI. METHODS:Consecutive patients who underwent successful elective CTO-PCI were prospectively enrolled from April 2019 to May 2021. After receiving 1-month DAPT, all patients were divided into two groups: SAPT group (followed by clopidogrel or ticagrelor monotherapy) and DAPT group (continued with dual antiplatelet therapy). Detailed baseline characteristics, angiographic and procedural details, and 1-year follow-up data were collected. The endpoints were major adverse cardiovascular events (MACE) and bleeding. RESULTS:A total of 701 patients who underwent successful CTO-PCI were enrolled, among whom 330 patients (47.1%) received DAPT and 371 patients (52.9%) received SAPT (clopidogrel or ticagrelor) after 1-month DAPT. Compared with patients receiving DAPT, patients in the SAPT (clopidogrel or ticagrelor) group had a lower rate of previous stroke, fewer left anterior descending coronary artery (LAD) lesions and contrast volume, and fewer lesions per patient, but longer lesion length (P < 0.05). The incidence of MACE (14.5% versus 15.4%; p = 0.742) was not significantly different between the two groups. The DAPT group showed a higher incidence of minor bleeding (BARC types 1 or 2; 12.7% versus 2.3%, p < 0.001) than SAPT (clopidogrel or ticagrelor), while no difference was found for major bleeding (BARC types 3 or 5; 1.2% versus 2.3%, p = 0.261). CONCLUSIONS:Compared with standard 12-month DAPT, 1-month DAPT followed by clopidogrel or ticagrelor monotherapy resulted in lower bleeding risks and similar cardiovascular benefits in CTO-PCI patients.

Background:KCNH2 encodes the hERG potassium channel, which is associated with drug-induced long QT syndrome. Arsenic trioxide (ATO) is an effective therapeutic agent for acute promyelocytic leukemia; however, its long-term use can lead to cardiotoxicity, particularly in cases of acquired long QT syndrome (acLQTS), which may result in torsade de pointes (TdP). Therefore, it is essential to comprehend the mechanisms behind acLQTS and to develop effective preventive and therapeutic strategies. Aim:This study sought to investigate the role and molecular mechanism of MALAT1 in ATO-induced acLQTS. Furthermore, it sought to identify pharmacological agents that could mitigate the cardiotoxic effects of ATO and establish viable intervention targets for the prevention and management of acLQTS. Methods:First, we employed gene chip arrays to identify target long noncoding RNAs (lncRNAs). Subsequently, we performed quantitative qRT-PCR and RNA-binding protein immunoprecipitation (RIP) to assess lncRNA levels. Next, we utilized Western blotting for protein expression analysis, and finally, we conducted whole-cell patch-clamp recordings to evaluate hERG currents. Results:Our results revealed a significant upregulation of lncRNA MALAT1 expression in HEK293-hERG cells treated with ATO. Mechanistically, MALAT1 interacts with calpain-1, inhibiting its ubiquitin-mediated degradation and enhancing the cleavage activity of calpain-1 on the hERG channel. FEX and TAN were found to mitigate the effects of ATO on the MALAT1/calpain-1 pathway, ultimately restoring hERG protein levels. Conclusion:This study demonstrated that ATO-induced enhancement of calpain-1 and reduction of hERG may be linked to the aberrant overexpression of lncRNA MALAT1. Tanshinone IIA and fexofenadine restored the hERG protein levels potentially by decreasing MALAT1 expression and counteracting ATO's effects on the MALAT1/calpain-1 pathway. Collectively, our research uncovers a previously unreported regulatory mechanism underlying ATO-induced acLQTS. Moreover, it identifies potential molecular targets and intervention strategies for acLQTS therapy.

OBJECTIVE:To investigate the rates of low disease activity and clinical remission in patients with systemic lupus erythematosus (SLE) in a real-world setting, and to analyze the related factors of low disease activity and clinical remission.METHODS:One thousand patients with SLE were enrolled from 11 teaching hospitals. Demographic, clinical and laboratory data, as well as treatment regimes were collec-ted by self-completed questionnaire. The rates of low disease activity and remission were calculated based on the lupus low disease activity state (LLDAS) and definitions of remission in SLE (DORIS). Charac-teristics of patients with LLDAS and DORIS were analyzed. Multivariate Logistic regression analysis was used to evaluate the related factors of LLDAS and DORIS remission.RESULTS:20.7% of patients met the criteria of LLDAS, while 10.4% of patients achieved remission defined by DORIS. Patients who met LLDAS or DORIS remission had significantly higher proportion of patients with high income and longer disease duration, compared with non-remission group. Moreover, the rates of anemia, creatinine elevation, increased erythrocyte sedimentation rate (ESR) and hypoalbuminemia was significantly lower in the LLDAS or DORIS group than in the non-remission group. Patients who received hydroxychloroquine for more than 12 months or immunosuppressant therapy for no less than 6 months earned higher rates of LLDAS and DORIS remission. The results of Logistic regression analysis showed that increased ESR, positive anti-dsDNA antibodies, low level of complement (C3 and C4), proteinuria, low household income were negatively related with LLDAS and DORIS remission. However, hydroxychloroquine usage for longer than 12 months were positively related with LLDAS and DORIS remission.CONCLUSION:LLDAS and DORIS remission of SLE patients remain to be improved. Treatment-to-target strategy and standar-dized application of hydroxychloroquine and immunosuppressants in SLE are recommended.

(-)-Epicatechin (EPI) is beneficial for cardiovascular health. Trimethylamine N-oxide (TMAO), a gut microbe-derived food metabolite, is strongly associated with the risk of cardiovascular diseases. However, the effects and underlying mechanisms of EPI on TMAO-induced cardiac hypertrophy remain unclear. This study aimed to determine whether EPI inhibits TMAO-induced cardiac hypertrophy. Plasma levels of TMAO in control participants and patients with cardiac hypertrophy were measured and analyzed. Male C57BL/6 mice were randomly divided into control group, TMAO group, EPI group and TMAO + EPI group. According to the groups assignments, mice received intraperitoneal (i.p.) injection of normal saline or i.p. injection of TMAO (150 mg/kg/day) for 14 days. The EPI group was given intragastric (i.g.) administration of EPI alone (1 mg/kg/day) for 21 days, and TMAO + EPI group received i.g. administration of EPI for 7 days before starting i.p. injection of TMAO, continuing until the end of the TMAO treatment. Histological analyses of the mice’s hearts was accessed by H E and Masson staining. In vitro, H9c2 cells were induced to hypertrophy by TMAO (10 µM) for 24 h and were pre-treated with or without EPI (10 µM) for 1 h. Protein level of cardiac hypertrophy markers and Sp1/SIRT1/SUMO1 pathway were determined by western blot. The plasma level of TMAO was 2.66 ± 1.59 μmol/L in patients with cardiac hypertrophy and 0.62 ± 0.30 μmol/L in control participants. EPI attenuated TMAO-induced hypertrophy in H9c2 cells. In vivo, TMAO induced cardiac hypertrophy and impaired the cardiac function of mice. Pathological staining showed that TMAO induced cardiac hypertrophy and collagen deposition in mice. EPI treatment improved the cardiac function, inhibited the myocardial hypertrophy induced by TMAO. EPI significantly attenuated the TMAO-induced upregulation of ANP and BNP and the downregulation of SP1, SIRT1 and SUMO1 in vivo and in vitro. EPI may suppress TMAO-induced cardiac hypertrophy by activating the Sp1/SIRT1/SUMO1 signaling pathway.

Background and Objective:Some patients continue to experience major adverse cardiovascular and cerebrovascular events(MACCE)after percutaneous coronary intervention(PCI)in frigid places.Indexes of inflammation and nutrition alone were shown to predict outcomes in patients with PCI.However,the clinical predictive value of mixed indicators is unclear.This study aimed to assess the predictive value of the albumin/neutrophil/lymphocyte ratio(NLR)on the long-term prognosis of patients with coronary heart disease(CHD)following percutaneous coronary intervention(PCI).Methods:A total of 608 post-PCI CHD patients were categorized into low-and high-index groups based on the optimal cut-off values for albumin and NLR.The primary outcome was a composite endpoint comprising all-cause mortality and major adverse cerebrovascular events.The secondary outcome was the comparison of the predictive efficiency of the new nutritional index,albumin/NLR,with that of albumin or NLR alone.Results:Over the five-year follow-up period,45 patients experienced the composite endpoint.The incidence of endpoint events was significantly higher in the low-index group(12%)compared to the high-index group(4.9%).Receiver operating characteristic(ROC)curve analysis revealed that the albumin/NLR index had a larger area under the curve(AUC:0.655)than albumin(AUC:0.621)or NLR(AUC:0.646),indicating superior predictive efficiency.The prognostic nutritional index had an AUC of 0.644,further supporting the enhanced predictive value of the albumin/NLR index over individual nutritional and inflammatory markers.Conclusion:The albumin/neutrophil/lymphocyte ratio is independently associated with the long-term prognosis of CHD patients post-PCI and demonstrates superior predictive efficiency compared to individual nutritional and inflammatory markers.

Background: To evaluate the factors affecting personal protective equipment (PPE) associated with headaches in healthcare workers during the first hit of coronavirus disease 2019 (COVID-19) outbreak in China in order to provide evidence for improving the prevention and treatment of PPE-associated headaches in frontline medical personnel. Methods: In this cross-sectional study, the baseline characteristics and the prevalence of the PPE-associated headaches among frontline healthcare workers at Wuhan Taikang Hospital were objectively evaluated by means of a questionnaire survey. We obtained predictors of PPE-associated headaches frequency by multiple regression analyses. The path analysis model was applied to determine the interrelationships between the variables related to PPE-associated headaches frequency. Results: Among the 520 participants, 436 (83.85 %) reported PPE-associated headaches during the anti-epidemic period. Compare with non-PPE-associated headache, age, PHQ-9 score >10, nurses, and PSQI>5were statistically significant found in participants with PPE-associated headaches. Multivariable linear regression showed that the occupation(nurse), pre-existing primary headache diagnosis, headache intensity and depression were risk factors for the frequency of PPE-associated headaches. The path analysis model observed that direct effects from occupation (nurse), pre-existing primary headache diagnosis, headache intensity and depression on the frequency of PPE-associated headaches. Depression indirectly mediated the effects of headache intensity and sleep quality on headache frequency. (All P < 0.05) Conclusion: This study provided a path analysis model that illustrates the relationships between PPE-associated headaches frequency and its related factors among healthcare workers during the COVID-19 pandemic. It is crucial to the management of PPE-associated headaches to reduce its consequences for frontline healthcare workers.

Introduction: Psoriasis (Pso) is an inflammatory autoimmune skin disease. High BMI, and elevated body fat and body weight is associated with risk of Pso development. People with Pso have lower physical activity than people without Pso, so they are at higher risk for comorbidities and underlying disease. Exercise has been shown to improve disease outcomes and inflammation in people with psoriasis. Aim: Meta-analysis study to investigate the physical activity in psoriasis patients Methods: We designed this study according to the Systematic Reviews and Meta-Analyses (PRISMA) statement. The ISI, Scopus, PubMed, Cochrane Library, and Google Scholar have been used to search articles up to the end of Results: A total of 1319 articles were extracted from the databases, and 7 articles were selected for analysis. High-intensity exercise levels were significantly lower in Pso patients than in healthy people (RR = 0.75; 95% CI: 0.60-0.93; p = 0.010). But there was no significant difference between the 2 groups regarding moderate-intensity exercise (RR = 0.80; 95% CI: 0.57-1.12; p = 0.20) and low-intensity exercise (RR = 1.42; 95% CI: 0.36-5.60; p = 0.62). Also, the number of metabolic equivalent task (MET) minutes in the Pso group was significantly lower than in healthy controls (SMD = -0.71; 95% CI: -0.86-0.56; p < 000001). Finally, the post-exercise PASI score decreased significantly in psoriatic patients (SMD = 3.98; 95% CI: 0.48-7.48; p = 0.03). Conclusions: High-intensity physical activity is significantly lower in Pso patients than in healthy people, MET in the Pso group was significantly lower than in healthy controls, and the post-exercise PASI score decreased significantly in psoriatic patients, which means physical activity intervention can be suggested as a therapeutic method for Pso patients.

BACKGROUND:To analyze the expression of TXLNA in brain gliomas and its clinical significance.METHODS:Gene Expression Profiling Interactive Analysis（GEPIA）and Chinese Glioma Genome Atlas（CGGA）databases were retrieved as the methods. To assess the disparity between TXLNA expression in glioma and normal brain tissue. The Kaplan-Meier survival curve was employed to preliminarily evaluate the survival curves of the high and low expression groups, this was done for investigate the correlation between TXLNA expression level and the survival and prognosis of glioma. A Cox proportional regression risk model of multivariate nature was employed to evaluate the elements impacting the survival and prognosis of glioma. Gene pool enrichment analysis（GSEA）was used to investigate the related function of TXLNA in glioma. A Pearson correlation test and co-expression analysis were employed to identify the genes most associated with TXLNA expression.RESULT:The enrichment analysis results were observably enriched in signal pathways for instance the cell cycle and completion and coordination cascade pathways, and it is evident that high expression of TXLNA in gliomas is related to a poor survival and a bad patient prognosis, thus making it an independent prognostic factor for gliomas. Genes such as STK40 and R1MS1 are significantly correlated with TXLNA, playing a synergistic or antagonistic role.CONCLUSIONS:The prognosis of GBM patients is strongly linked to the high expression of TXLNA, which may be a viable therapeutic target for curbing cancer progression and creating new immunotherapies for GBM.

Abstract Background Pulmonary arterial hypertension is a major cause of death in systemic lupus erythematosus, but there are no tools specialized for predicting survival in systemic lupus erythematosus-associated pulmonary arterial hypertension. Research question To develop a practical model for predicting long-term prognosis in patients with systemic lupus erythematosus-associated pulmonary arterial hypertension. Methods A prognostic model was developed from a multicenter, longitudinal national cohort of consecutively evaluated patients with systemic lupus erythematosus-associated pulmonary arterial hypertension. The study was conducted between November 2006 and February 2020. All-cause death was defined as the endpoint. Cox regression and least absolute shrinkage and selection operators were used to fit the model. Internal validation of the model was assessed by discrimination and calibration using bootstrapping. Results Of 310 patients included in the study, 81 (26.1%) died within a median follow-up of 5.94 years (interquartile range 4.67–7.46). The final prognostic model included eight variables: modified World Health Organization functional class, 6-min walking distance, pulmonary vascular resistance, estimated glomerular filtration rate, thrombocytopenia, mild interstitial lung disease, N-terminal pro-brain natriuretic peptide/brain natriuretic peptide level, and direct bilirubin level. A 5-year death probability predictive algorithm was established and validated using the C-index (0.77) and a satisfactory calibration curve. Risk stratification was performed based on the predicted probability to improve clinical decision-making. Conclusions This new risk stratification model for systemic lupus erythematosus-associated pulmonary arterial hypertension may provide individualized prognostic probability using readily obtained clinical risk factors. External validation is required to demonstrate the accuracy of this model's predictions in diverse patient populations.

The aim of this work is to verify the non-inferior efficacy and safety of CMAB008 compared with innovator infliximab in rheumatoid arthritis patients combined with methotrexate. We conducted a randomized, double-blinded, parallel, positive control design, multicenter study, with a stable dose of methotrexate. Patients were enrolled randomly with a ratio of 1:1 to receive intravenously CMAB008 3 mg/kg or innovator infliximab 3 mg/kg at weeks 0, 2, 6, 14, 22 and 30. The primary efficacy endpoint was American College of Rheumatology 20

Introduction:Ulcerative colitis (UC) is an inflammatory bowel disease characterized by recurrent and remitting inflammation of the mucosa of the colon and rectum, the incidence of which is on the rise. Glucagon-like peptide-2 (GLP-2) is a newly discovered neurotrophic factor, but its efficacy and mechanism of action in UC remain unclear. In this study, we investigated the protective effects and potential targets of GLP-2 on dextran sodium sulfate (DSS)-induced UC in mice through integrative analysis.Methods:The effects of GLP-2 on UC were assessed by calculating the disease activity index, colonic mucosal damage index, and pathological histological scores. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were used to detect the expression of GLP-2, nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6), and signal transducer and activator of transcription-3 (STAT3). The 16SrRNA gene was used to detect changes in gut microbiota in mouse colonic tissues, and oral glucose tolerance test (OGTT) blood glucose levels were used to analyze the differences in flora.Results:The results showed that GLP-2 could reduce the inflammation of UC mice, which may be achieved by inhibiting the potential targets of NF-κB, and Janus kinase (JAK)/STAT3 inflammatory pathways, regulating sugar metabolism, increasing dominant species, and improving microbial diversity.Discussion:This study provides new insight into the potential of GLP-2 for achieving more ideal UC treatment goals in future.

Developing new nanoplatforms for dynamically and quantitatively visualizing drug accumulation and targeting within tumors is crucial for precision cancer theranostic. However, achieving efficient tumor therapy via synergistic photothermal/photodynamic therapy (PTT/PDT) using a single excitation light source, remains a challenge. In this work, we designed Gd-surface functionalized copper sulfide nanoparticles that were modified with folic acid (FA) (Cu1.96S-Gd@FA) to overcome the above limitations and promote PTT/PDT therapeutics. Here, Cu1.96S-Gd nanoparticles were synthesized via a coprecipitation method. All samples exhibited high longitudinal relaxivity (up to 12.9 mM-1 s-1) and strong photothermal conversion efficiency (50.6%). Furthermore, the Gd ions promoted electron-hole segregation, inducing the Cu1.96S-Gd nanoparticles to generate more reactive oxygen species (ROS) than pure Cu1.96S nanoparticles. The Cu1.96S-Gd@FA enabled the targeting of folate receptor (FR) and promoted cellular uptake, consequently enhancing oncotherapy efficacy. Compared to non-targeted Cu1.96S-Gd, a higher signal enhancement for magnetic resonance (MR) imaging in vivo by Cu1.96S-Gd@FA was recorded. Given photothermal ability, the nanoparticles also could be visualized in infrared (IR) imaging. Furthermore, the nanoparticles exhibited biodegradation behavior and achieved good drug elimination performance via renal clearance. Our strategy, integrating Cu1.96S-Gd@FA nanoparticles, MR/IR dual modal imaging, and PTT/PDT into one nanoplatform, demonstrated great potential for anti-breast cancer therapy by effectively targeting FR overexpressed breast cancer cells. (C) 2022 Elsevier Inc. All rights reserved.

Objective: This study evaluated the prognostic value of the multivariable risk assessment for systemic lupus erythematosus (SLE)-associated pulmonary arterial hypertension (PAH). Methods: A multicenter prospective cohort of SLE-associated PAH (CSTAR-PAH cohort) diagnosed based on right heart catheterization (RHC) was established. Baseline and follow-up records were collected. Three methods of risk assessment, including (1) the number of low-risk criteria, based on World Health Organization functional class (WHO FC), 6-min walking distance (6MWD), right atrial pressure (RAP), and cardiac index (CI); (2) the three-strata stratification based on the average risk score of four variables (WHO FC, 6MWD, RAP, and CI); and (3) the four-strata stratification based on COMPARE 2.0 model were applied. A risk-assessment method using three noninvasive low-risk criteria was applied at the first follow-up visit. Survival curves between patients with different risk groups were compared by Kaplan–Meier’s estimation and log-rank test. Results: Three-hundred and ten patients were enrolled from 14 PAH centers. All methods of stratification at baseline and first follow-up significantly discriminated long-term survival. Survival rates were also significantly different based on the noninvasive risk assessment in first follow-up visit. Survival deteriorated with the escalation of risk from baseline to first follow-up. Patients with baseline serositis had a higher rate of risk improvement in their follow-up. Conclusion: The risk assessment has a significant prognostic value at both the baseline and first follow-up assessment of SLE-associated PAH. A noninvasive risk assessment can also be useful when RHC is not available during follow-up. Baseline serositis may be a predictor of good treatment response in patients with SLE-associated PAH.

Cyclosporin A (CsA) is a well-known and effective drug that is commonly used in autoimmune diseases and allotransplantation. However, kidney toxicity and cardiotoxicity limit its use. Circular RNAs (circRNAs) play a crucial role in disease, especially cardiovascular disease. We aimed to explore the circRNA expression profiles and potential mechanisms during CsA-induced cardiotoxicity. Sixty male adult Wistar rats were randomly divided into two groups. The CsA group was injected with CsA (15 mg/kg/day body weight) intraperitoneally (ip) for 2 weeks, whereas the control group was injected ip with the same volume of olive oil. We assessed CsA-induced cardiotoxicity by light microscopy, transferase-mediated dUTP nick-end labeling (TUNEL) staining, and electron microscopy. Microarray analysis was used to detect the expression profiles of circRNAs deregulated in the heart during CsA-induced cardiotoxicity. We confirmed the changes in circRNAs by quantitative PCR. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the microarray data were performed. A conventional dose of CsA induced cardiotoxicity in rats. We identified 67 upregulated and 37 downregulated circRNAs compared with those in the control group. Six of 12 circRNAs were successfully verified by quantitative real-time polymerase chain reaction (qRT-PCR). GO analyses of the differentially expressed circRNAs indicated that these molecules might play important roles in CsA-induced cardiotoxicity. KEGG pathway analyses showed that the differentially expressed circRNAs in CsA-induced cardiotoxicity may be related to autophagy or the Hippo signaling pathway. We identified differential circRNA expression patterns and provided more insight into the mechanism of CsA-induced cardiotoxicity. CircRNAs may serve as potential biomarkers or therapeutic targets of CsA-mediated cardiotoxicity in the future.

Abstract Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by recurrence and remission of colonic and rectal mucosal inflammation, and its incidence is increasing year by year. Glucagon-like peptide-2 (GLP-2) is a newly discovered enteral nutrition factor, but its efficacy and potential mechanism of action on UC have not been fully elucidated. Aims The purpose of this study was to investigate the protective effect of GLP-2 on Dextran sulfate sodium (DSS) -induced UC in mice and its potential mechanism. Methods 40 C57BL/6J female mice were randomly divided into 4 groups: control group (CON) ,DSS group (DSS) ,DSS + Enterotoxigenic Escherichia coli group (ETEC) ,DSS + ETEC + sitagliptin group (GLP-2). The effect of GLP-2 on UC was evaluated by calculating the disease activity index (DAI), colonic mucosal damage index (CMDI), and histopathological score. The expressions of GLP-2, nuclear factor κB (NF-κB), Interleukin-6 (IL-6), and signal transducer and activator of transcription 3 (STAT3) were detected by the Enzyme-Linked Immunosorbent Assay (ELISA ) and immunohistochemistry. 16SrRNA was used to detect the changes in gut microbiota in mouse colonic tissue. Results Compared with the control group, the GLP-2 of mice in the DSS group and ETEC group decreased significantly, and NF-κB, IL-6, and STAT3 were significantly increased(P < 0.0001). Compared with the DSS group, the CMDI score and histopathological score of the GLP-2 group were significantly decreased, GLP-2 expression was significantly increased, and NF-κB, IL-6, and STAT3 were significantly decreased. The results of 16SrRNA detection showed that compared with the DSS group, the dominant bacteria such as Lactobacillus and Prevotellaceae were increased and the diversity of gut microbiota was increased in the GLP-2 group. Conclusions GLP-2 reduced the degree of inflammation in UC mice, which may be achieved by inhibiting the inflammatory pathways of NF-κB and Janus Kinase (JAK) /STAT3, increasing the dominant bacteria and improving the diversity of gut microbiota.

Ulcerative colitis (UC) is a chronic inflammatory disease of the intestine. It is characterized with recurrent. The pathogenesis is mainly associated with environmental factors, genetic susceptibility, dysbiosis of the intestinal flora and autoimmunity. The role of intestinal flora disorders in the pathogenesis and progression of UC is becoming increasingly prominent. More and more studies have confirmed that fecal microbiota transplantation (FMT) could reshape the composition of UC intestinal flora and it is expected to be a new strategy for UC treatment. In this study, we used 2% Dextran sulfate sodium (DSS) for 7 days to induce acute colitis model in mice, and interfere with FMT and Enterotoxigenic Escherichia coli (ETEC). ELISA and immunohistochemistry were applied to detect the concentration and expression of NF-κB p65, STAT3 and IL-6. 16SrRNA high-throughput sequencing was performed to explore the composition of intestinal flora. The aim was to study the treatment effect of FMT on UC mice and explore its potential mechanism by observing the changes of intestinal flora composition and diversity, and its relationship with NF-κB p65, STAT3 and IL-6 expression. We conclude that FMT could improve intestinal flora disorder in mice with ulcerative colitis, regulate NF-κB signaling pathway, and significantly reduce intestinal inflammation in UC mice.

No previous studies have investigated the predictive performance of the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL) prognostic equation and simplified risk score calculator in patients with systemic lupus erythematosus-associated pulmonary arterial hypertension (SLE-PAH). We aimed to validate these prediction tools in an external cohort of patients with SLE-PAH. In this study, the validation cohort consisted of patients with SLE-PAH registered in a prospective, multicenter, nationwide database between November 2006 and May2016. The follow-up of patients was censored at 1 year. Discrimination, calibration, model fit, and risk stratification of the REVEAL prognostic equation and simplified risk score calculator were validated. As a result, a total of 306 patients with SLE-PAH were included. The 1-year overall survival rate was 91.5%. The C-index of the prognostic equation was 0.736, demonstrating reasonably good discrimination, and it was greater than that for the simplified risk score calculator (0.710). The overall calibration slope was 0.83, and the Brier score was 0.079. The risk of renal insufficiency and World Health Organization Functional Class III (WHO FC III) were underestimated, and the risk assigned to a heart rate >92 bpm in the REVEAL prognostic models was not observed in our validation cohort. Both model discrimination and calibration were poor in the very high-risk group. In conclusion, the REVEAL models exhibit good discriminatory ability when predicting 1-year overall survival in patients with SLE-PAH. Findings from both models should be interpreted with caution in cases of renal insufficiency, WHO FC III, and heart rate >92 bpm.