Explore the vast range of titles available.

Breast cancer is a leading cause of cancer-related mortality, and the most prevalent malignant neoplasm amongst women worldwide. This study aimed to explore the role of FAM134B in breast cancer progression. The correlation between FAM134B expression and the prognosis of breast cancer patient was analyzed using the Kaplan-Meier Plotter database. qRT-PCR was used to quantify mRNA level, whereas western blotting was employed to detect th expression of FAM134B, autophagy-associated proteins, and endoplasmic reticulum (ER) stress related proteins. Cell proliferation was assessed via CCK-8 and colony formation assays. Cell apoptosis rate was measured by flow cytometry. Autophagosomes formation was observed under a transmission electron microscopy, and the expression of LC3 protein in cells was detected by immunofluorescence. The function of FAM134B was verified using a tumor xenograft model in nude mice. High expression of FAM134B in breast cancer patients was correlated with reduced overall survival and disease-free survival. Both FAM134B mRNA and protein levels were significantly higher in breast cancer cells than normal breast epithelial cells. Downregulation of FAM134B suppressed the proliferation of breast cancer cells and increased their apoptosis rates. Furthermore, silencing FAM134B triggered autophagy and ER stress in breast cancer. In nude mice, FAM134B knockdown also inhibited breast cancer progression and induced autophagy. Downregulation of FAM134B inhibited the development of breast cancer through inducing apoptosis, autophagy, and ER stress of breast cancer cells.

Background Ferroptosis and disulfidptosis are newly discovered forms of regulated cell death that play critical roles in cancer progression, metabolism, and immune evasion. However, their interplay and combined influence on colorectal cancer (CRC) progression remain insufficiently understood. Methods We developed a ferroptosis-disulfidptosis-related gene (FDRG) score using machine-learning algorithms to analyze gene modifications associated with these pathways in CRC, utilizing data from the TCGA and GEO databases. The model was externally validated, and associations with clinical outcomes, immune infiltration, mutational landscapes, immunotherapy responses, and drug sensitivity were explored. Key genes were further investigated through bioinformatics and in vitro experiments. Results We constructed an 8-gene risk model with strong prognostic value, stratifying CRC patients into high- and low-risk groups with significant differences in clinical characteristics, immune cell infiltration, and therapeutic responses. Among these genes, CHMP6 was identified as a previously uncharacterized tumor suppressor in CRC. Beyond its inhibitory effect on tumor cell proliferation, migration, and invasion, CHMP6 was found to play a critical role in modulating anti-tumor immunity. Our findings established CHMP6 as a dual-function tumor suppressor that not only restrains tumor progression but also enhances immune-mediated tumor control. Conclusions The FDRG score is a robust tool for predicting CRC prognosis, tumor microenvironment dynamics, and response to immunotherapy. CHMP6 emerged as a promising tumor suppressor and potential therapeutic target, offering new insights into CRC treatment strategies.

Objective This study aimed to compare hospital and long-term clinical outcomes associated with various treatment methods for Stanford A type aortic intramural hematoma (IMH) to provide a reference for clinical decision-making. Methods In this single-center cohort study, we retrospectively analyzed 73 patients with Type A IMH treated at our center from August 1, 2018 to August 1, 2021. Among these patients, 26 were treated conservatively, and 47 underwent surgical intervention. We next compared this IMH cohort with 154 patients with acute type A aortic dissection (AD) who were treated surgically during the same study period. Results Computed tomography angiography revealed that the diameter of the ascending aorta of IMH patients treated with surgery was higher than IMH patients treated with conservative therapy (44.92 ± 7.58 mm vs. 51.22 ± 11.85 mm, P  < 0.05), while there was no significant difference in other clinical parameters. The in-hospital mortality of patients with IMH who underwent surgical treatment was lower than those undergoing conservative treatment (0% vs. 11.5%, P  < 0.05). The long-term mortality of the conservative IMH group was higher than the surgical IMH group (26.1% vs. 8.5%, P  < 0.05). There was no significant difference in the surgical parameters and postoperative complications between AD and IMH surgery patients. The proportion of circulatory arrest time in the lower body (19.98 ± 9.39 min vs. 17.51 ± 3.97 min) and arch involvement (98 (63.6%) vs. 22 (46.8%)) in the IMH surgery group was lower than in the AD surgery group ( P  < 0.05). Conclusions Compared with conservative treatment, surgical treatment of IMH significantly improves the survival rate of patients. Thus, surgical intervention should be considered the primary treatment option if feasible. Furthermore, The safety of IMH surgery can be guaranteed just like AD. But we still need in the future evidence on bigger samples. Graphical abstract

Background Most colorectal cancers are resistant to immune checkpoint inhibitors due to an immunosuppressive tumor microenvironment. LINC00673, previously classified as a long non-coding RNA, has been implicated in tumor progression, but its role in antitumor immunity remains poorly understood. Methods We used single-cell RNA sequencing, flow cytometry, and functional assays in Linc00673 knockout and wild-type mouse models treated with programmed death 1 (PD-1) blockade to dissect changes in immune landscape and tumor cell behavior. Results Linc00673 deletion enhanced the efficacy of PD-1 therapy, reducing tumor burden and prolonging survival. KO tumors showed increased infiltration of cytotoxic CD8⁺ T cells, reduced exhaustion, and improved antigen presentation. The tumor microenvironment shifted toward a pro-inflammatory state, with elevated dendritic cell function, reduced immunosuppressive macrophages, and improved T cell–tumor interactions. Linc00673 also promoted tumor cell migration and immune evasion independently of immune cells, suggesting dual tumor-intrinsic and -extrinsic roles. Conclusions LINC00673 suppresses antitumor immunity and promotes tumor aggressiveness. Its deletion synergizes with PD-1 blockade, revealing a promising therapeutic target to overcome immune resistance in colorectal cancer.

Hypertrophic cardiomyopathy (HCM) is characterized by cardiac hypertrophy and fibrosis. To investigate the impact of CARMA3 on fibroblast phenotypic transformation in hypertrophic cardiomyopathy (HCM), the correlation between CARMA3 expression and fibrosis was analyzed in HCM patients. Cardiac function and fibroblast phenotypic transformation were assessed in wild-type and CARMA3-knockout mice subjected to transverse aortic constriction (TAC) or angiotensin II treatment. Additionally, cardiac fibroblasts were screened using flow cytometry and proteomic analysis to identify potential targets. Significant cardiac functional impairment and fibrosis were observed in CARMA3-knockout mice following TAC or angiotensin II treatment. Primary fibroblasts isolated from these mice exhibited increased myofibroblast differentiation, extracellular collagen production, mitochondrial damage, and macrophage inflammation. Elevated STAT1 expression was identified in cardiac fibroblasts from CARMA3-knockout mice through proteomic analysis. Additionally, STAT1 phosphorylation was regulated by CARMA3, and an interaction between CARMA3 and STAT1 was detected in response to pressure overload. In conclusion, CARMA3 may suppress myofibroblast activation by inhibiting STAT1 phosphorylation, thereby improving myocardial fibrosis in pressure overload-induced HCM.

Myocardial fibrosis, oxidative stress, and autophagy both play key roles in the progression of adverse cardiac remodeling. Stomatin-like protein 2 (SLP-2) is closely related to mitochondrial function, but little is known about its role and mechanism in cardiac remodeling. We developed doxorubicin (Dox), angiotensin (Ang) II, and myocardial ischemia-reperfusion (I/R) injury induced cardiac remodeling model and Dox treated H9C2 cell injury model using SLP-2 knockout (SLP-2 -/- ) mice and H9C2 cells with low SLP-2 expression. We first examined cardiac functional and structural changes as well as levels of oxidative stress, apoptosis and autophagy. We found that SLP-2 deficiency leads to decreased cardiac function and promotes myocardial fibrosis. After Dox and Ang II treatment, SLP-2 deficiency further aggravated myocardial fibrosis, increased myocardial oxidative stress and apoptosis, and activated autophagy by inhibiting PI3K-Akt-mTOR signaling pathway, ultimately exacerbating adverse cardiac remodeling. Similarly, SLP-2 deficiency further exacerbates adverse cardiac remodeling after myocardial I/R injury. Moreover, we extracted cardiomyocyte mitochondria for proteomic analysis, suggesting that SLP-2 deficiency may be involved in myocardial I/R injury induced adverse cardiac remodeling by influencing ubiquitination of intramitochondrial proteins. In addition, the oxidative stress, apoptosis and autophagy levels of H9C2 cells with low SLP-2 expression were further enhanced, and the PI3K-Akt-mTOR signaling pathway was further inhibited under Dox stimulation. Our results suggest that SLP-2 deficiency promotes myocardial fibrosis, disrupts normal mitochondrial function, overactivates autophagy via PI3K-Akt-mTOR signaling pathway, affects the level of ubiquitination, leads to irreversible myocardial damage, and ultimately exacerbates adverse cardiac remodeling.

Background Over the past decade, minimally invasive mitral valve surgery (MIMVS) has grown in popularity. Less invasive approaches to mitral valve surgery are increasingly used for improved cosmesis. We sought to compare these minimally invasive approaches fairly with conventional full sternotomy approaches by using propensity-matching methods. Methods From January 2011 to January 2017, a total of 1120 isolated mitral valve operations were performed at our institution. Data were retrospectively collected on all patients, and a logistic regression model was created to predict selection to a minimally invasive versus conventional sternotomy approach. Propensity scores were then generated based on the regression model and matched pairs created using 1:1 nearest neighbor matching. There were 165 matched pairs in the analysis (sternotomy, n  = 165;MIMVS, n = 165). Clinical outcomes included bypass and cross-clamp time, length of hospitalization, morbidity, and mortality. Patient details and follow-up outcomes were compared using multivariate, and Kaplan–Meier analyses. Results The minimally invasive approach led to slightly longer cardiopulmonary bypass time (99 ± 25 vs 88 ± 17 min, p <0.001), and cross-clamp time (65 ± 13 vs 49 ± 11 min, p <0.001). Overall, no significant differences existed among major in-hospital complications between groups. There were no differences between the matched groups in 30-day mortality (1.2% vs 0.6%, p >0.05). However, Chest tube drainage was lower at 6 and 24 h after a minimally invasive approach (30 ± 5 mL) and 120 ± 20 mL than after conventional sternotomy 175 ± 50 mL and 400 ± 150 mL at these times ( p  < 0.001). Transfusion was less frequent after minimally invasive surgery than after conventional surgery (15.7% vs 40.6%, p  < 0.001). Patients undergoing minimally invasive surgery spent less time on ventilation support (6.2 ± 1.1 h vs 10.4 ± 2.7, p  < 0.001). The multivariable regression analysis showed the full sternotomy was an independent risk factor for the propensity-adjusted likelihood of postoperative transfusion, re-exploration for bleeding, and postoperative ventilation support ( p  < 0.05). But the duration of cardiopulmonary bypass time was not an independent risk factor. The mean duration of survival follow-up was 4.4 ± 1.2 years. However, comparison of survival curves between the two groups revealed no significant difference ( P  = 0.203). With regard to freedom from valve-related morbidity, there was no significant difference between groups (P = 0 .574). Conclusion Within that portion of the spectrum of mitral valve surgery in which propensity matching was possible, minimally invasive mitral valve surgery has cosmetic, blood product use, and respiratory advantages over conventional surgery, and no apparent detriments. However, minimally invasive mitral valve surgery required a slightly longer cardiopulmonary bypass time and cross-clamp time. Minimally invasive mitral valve surgery represents a safe and effective surgical technique that we believe should be used more routinely in the surgical management of mitral valve disease. MIMVS provides equally durable midterm results as the standard sternotomy approach.

Background Diffuse coronary artery disease is a challenge for both percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). Coronary artery endarterectomy (CE) coupled with CABG is an alternative method to achieve complete revascularization. The mid- and long-term results of CE are largely questionable. The aim is to evaluate the early and mid-term graft patency of concomitant coronary artery endarterectomy and CABG. Methods A total of 304 patients who had undergone concomitant CE and CABG for diffuse coronary artery disease were identified from our database. A total of 238 patients (1) with complete operative records, (2) with good graft flow during surgery, (3) who were discharged, (4) with a one-year/ three-year follow-up were included in our study. The follow-up information was obtained directly from our out-patient department and by telephone contact. The categorical and continuous values were analyzed by Chi Square test and student’s test respectively. Results CE was performed on 238 patients who represented a total of 269 target coronary vessels. The mean age of the patients was 67.8 ± 6.8 years old; male to female patient ratio was 170:68. The mean intensive care unit stay was 1.7 ± 8 days, and mean post-operative length of hospital stay was 11 ± 3 days. The average follow up time was 41.8 ± 21.4 months. At follow-up, the overall graft patency was 78.4% at one year and 69.8% at three years. The left coronary graft patency rate was significantly higher than the right coronary graft patency rate (87.4% vs 73.1% at one-year and 78.2% vs 64.8% at three years). There was no significant difference in graft patency rates between the on-pump CE + CABG vs off-pump CE + CABG groups at one year (80.0% vs 76.9%) and at three years (92.3% vs 91.7%). At the one-year follow up, 92.3% of grafts showed grade A patency in the on-pump group versus 91.7% in the off-pump group; 7.7% of grafts showed grade B patency in the on-pump group versus 8.3% in the off-pump group. At the three-year follow up, 80.6% of grafts showed grade A patency in the on-pump group versus 77.4% in the off-pump group; 19.4% of grafts showed grade B patency in the on-pump group versus 22.6% in the off -pump group. The Predictors of better graft patency are use of LIMA graft, CE on LAD, and intra-operative graft flow meter and PI. Conclusions In patients with diffuse coronary disease, CE is a safe and feasible technique for a select group of patients with excellent mid-term survival rates and graft patency rates. CE produces better overall results when performed on the LAD, and grafted over with the LIMA. Similar outcomes are obtained with both on-pump and off-pump surgery. For a select group of patients, coronary endarterectomy (CE) offers an alternative choice of coronary artery reconstruction and complete coronary revascularization.

Background There is controversy regarding the choice of prosthetic valves in patients with cardiac valve disease and dialysis-dependent patients. This review assesses a 12-year experience and outcomes after valve replacement in patients on chronic preoperative renal dialysis, comparing survival and valve-related outcomes following valve replacement with bioprostheses versus mechanical prostheses in this population in china. Methods From January 1999 and October 2011, 73 consecutive dialysis patients underwent cardiac valve replacement. The patients were divided into two groups: (Group B) bioprosthesis valves were implanted in 38 (52.1%) patients and (Group M) mechanical valves were implanted in 35 (47.9%) patients. Outcome measures included perioperative data, hospital mortality, major postoperative complications, follow-up outcomes, valve related morbidity and late survival. Results There were no significant differences in terms of patient characteristics in the 2 groups. Thirty-three were isolated aortic valve replacements (45.2%); 28 were isolated mitral valve replacements (38.4%); 10 were combined aortic and mitral replacements (13.7%); 2 were combined tricuspid and mitral replacements (2.7%). The overall hospital mortality was 5.5% (n = 4) and was not different between Group B (5.3%) and Group M (5.7%). Low ejection fraction was the only independent predictors of hospital mortality. There was no significant difference between the groups in the overall rate of complications. The overall mean follow-up was 47 ± 23 months. According to the Kaplan-Meier analysis, late mortality, perivalvular leak and freedom from reoperation were similar in patients with mechanical and bioprosthesis valves. The bioprosthesis valve group had significantly higher freedom from thromboembelism-bleeding events (100% versus 77.6 ± 11.0%, p = 0.012), and valve-related morbidity (73.2 ± 10.1% versus 58.1 ± 10.9%, p = 0.035) in 5 years. Kaplan–Meier survival estimates at 1, 3, and 5 years were 0.971, 0.832, and 0.530 in group B, and 0.967, 0.848, and 0.568 in group M. Conclusions There is no significant difference in the perioperative morbidity and mortality, late survival of dialysis patients after cardiac valve replacement with bioprostheses versus mechanical valves. In spite of the limited sample size analyzed, its outcome and consistency to several previous reports supports a conclusion that bioprostheses rather than mechanical ones could be a favorable choice for valve replacement needs of renal failure patients.

Doxorubicin (DOX) is an effective chemotherapeutic drug, but its use can lead to cardiomyopathy, which is the leading cause of mortality among cancer patients. Macrophages play a role in DOX-induced cardiomyopathy (DCM), but the mechanisms undlerlying this relationship remain unclear. This study aimed to investigate how IKKα regulates macrophage activation and contributes to DCM in a mouse model. Specifically, the role of macrophage IKKα was evaluated in macrophage-specific IKKα knockout mice that received DOX injections. The findings revealed increased expression of IKKα in heart tissues after DOX administration. In mice lacking macrophage IKKα, myocardial injury, ventricular remodeling, inflammation, and proinflammatory macrophage activation worsened in response to DOX administration. Bone marrow transplant studies confirmed that IKKα deficiency exacerbated cardiac dysfunction. Macrophage IKKα knockout also led to mitochondrial damage and metabolic dysfunction in macrophages, thereby resulting in increased cardiomyocyte injury and oxidative stress. Single-cell sequencing analysis revealed that IKKα directly binds to STAT3, leading to the activation of STAT3 phosphorylation at S727. Interestingly, the inhibition of STAT3-S727 phosphorylation suppressed both DCM and cardiomyocyte injury. In conclusion, the IKKα-STAT3-S727 signaling pathway was found to play a crucial role in DOX-induced cardiomyopathy. Targeting this pathway could be a promising therapeutic strategy for treating DOX-related heart failure.