A single-pixel and non-redundant branching-based algorithm for nailfold capillary skeleton line extraction.

Background: Static nailfold capillary parameters are important parameters that reflect the health of the human body. Disease onset or progression is often accompanied by changes in the physiological parameters of the nailfold. Hence, the physiological parameters of the nailfold are closely related to the study of disease, with their automated and high-precision measurements playing a crucial role in these studies. Currently, manually measured values of the nailfold's parameters are the gold standard; however, they are time consuming and labor intensive, making the development of automated measurement methods essential. Most automated measurement methods use skeleton lines; however, current skeleton-thinning algorithms have non-single pixels and redundant branches that lead to reduced measurement accuracy. This study proposes a single-pixel and non-redundant branching-based skeleton line extraction algorithm for nailfold capillaries, which is then applied to nailfold static parameter calculations to improve accuracy. Methods: The algorithm includes deletion and restoration templates combined with the depth-first search method to obtain single-pixel skeleton lines without redundant branches. These lines are applied to the static nailfold capillary parameter measurement method based on digital image processing to calculate the blood vessel diameter. Results: The results show that the proposed method can obtain the single-pixel skeleton line without the redundant branches that are required for the parameter calculations and improve the accuracy of the nailfold capillary diameter measurement. Experiments showed that the root mean square errors (RMSEs) of the labeled apical diameter, arterial limb diameter, and venous limb diameter were 0.794, 0.756, and 0.830 µm, respectively, when the calculated results were compared with those of the manual calculations. According to the accuracy formula, the accuracy of the method in this study is 90%. We calculated the P values of the algorithmic and manual measurements to P<0.001 and found that the difference in the measurements of the proposed algorithm is statistically significant. Therefore, the method in this study has high sensitivity and specificity for the measurement of normal nailfold capillaries. Conclusions: The proposed algorithm could obtain single-pixel skeleton lines without redundant branches, thereby improving the nailfold static parameter measurement accuracy.

Caffeic acid inhibits Staphylococcus aureus-induced endometritis through regulating AMPKα/mTOR/HIF-1α signalling pathway.

Endometritis is mostly caused by childbirth or postpartum uterine infection. It is one of the important reasons leading to female infertility. Caffeic acid (CA) and its derivatives are widely found in some foods and traditional Chinese medicine, and have biological activities such as antioxidant, free radical scavenging, anti-inflammatory, and anti-infection. In this study, we aimed to explore the effect of CA on Staphylococcus aureus-induced endometritis. The contents of TNF-α and IL-1ß were detected by ELISA in S. aureus-induced endometritis model. Western blot assay was used to detect the expression of AMPKα/mTOR/HIF-1α pathway related proteins and GPX4 expression. In addition, the concentrations of MDA, GSH, and iron were tested by the assay kits. Compared with the model group, CA treatment significantly alleviated S. aureus-induced uterine injury, MPO activity, the contents of inflammatory factors TNF-α and IL-1ß, and NF-κB activation. Meanwhile, CA significantly inhibited S. aureus-induced ferroptosis, as confirmed by decreased MDA and iron concentration and up-regulated GPX4 expression and GSH level. Furthermore, CA attenuated S. aureus-induced HIF-1α and phosphorylated mTOR expression and increased phosphorylated AMPK expression. In conclusion, CA inhibits inflammation and ferroptosis by regulating AMPKα/mTOR/HIF-1α signalling pathway to alleviate S. aureus-induced endometritis in mice.

Dysregulation and impaired anti-bacterial potential of mucosal-associated invariant T cells in autoimmune liver diseases.

Autoimmune liver diseases (AILD) encompass a group of conditions in which the immune system mistakenly attacks the liver tissue. Mucosal-associated invariant T (MAIT) cells are enriched in the liver, where they play crucial roles in antibacterial defense and inflammation regulation. Compared to other autoimmune conditions affecting the synovium of the joints, MAIT cells from AILD exhibited a greater deficiency in ratio, elevated activation markers, increased apoptosis, and higher pro-inflammatory cytokines production. However, the frequency of MAIT cells in AILD was negatively correlated with anti-bacterial indexes, and their impaired responsiveness and weakened anti-bacterial potential were evidenced by reduced expansion ability, lower maximal IFN-γ production, and diminished E. coli-induced cytotoxic mediators release. Similar shifts in MAIT cell ratios and phenotypes were observed in both primary biliary cirrhosis and autoimmune hepatitis, linked to upregulation of bile acid components in the affected tissue. Specifically, ursodeoxycholic acid, a metabolic intermediate and traditional anti-primary biliary cirrhosis drug, inhibited TCR-mediated expansion and downregulated pro-inflammatory cytokines and anti-bacterial-related mediators in MAIT cells. These findings underscore the intricate interplay between hepatic pathology and MAIT cells, and highlight the importance of antibacterial monitoring during ursodeoxycholic acid treatment in AILD.

Momordica charantia L.-derived exosome-like nanovesicles stabilize p62 expression to ameliorate doxorubicin cardiotoxicity.

BACKGROUND: Doxorubicin (DOX) is a first-line chemotherapeutic drug for various malignancies that causes cardiotoxicity. Plant-derived exosome-like nanovesicles (P-ELNs) are growing as novel therapeutic agents. Here, we investigated the protective effects in DOX cardiotoxicity of ELNs from Momordica charantia L. (MC-ELNs), a medicinal plant with antioxidant activity. RESULTS: We isolated MC-ELNs using ultracentrifugation and characterized them with canonical mammalian extracellular vesicles features. In vivo studies proved that MC-ELNs ameliorated DOX cardiotoxicity with enhanced cardiac function and myocardial structure. In vitro assays revealed that MC-ELNs promoted cell survival, diminished reactive oxygen species, and protected mitochondrial integrity in DOX-treated H9c2 cells. We found that DOX treatment decreased the protein level of p62 through ubiquitin-dependent degradation pathway in H9c2 and NRVM cells. However, MC-ELNs suppressed DOX-induced p62 ubiquitination degradation, and the recovered p62 bound with Keap1 promoting Nrf2 nuclear translocation and the expressions of downstream gene HO-1. Furthermore, both the knockdown of Nrf2 and the inhibition of p62-Keap1 interaction abrogated the cardioprotective effect of MC-ELNs. CONCLUSIONS: Our findings demonstrated the therapeutic beneficials of MC-ELNs via increasing p62 protein stability, shedding light on preventive approaches for DOX cardiotoxicity.

[Authenticity discrimination for Galli Gigerii Endothelium Corneum based on UPLC-MS/MS and peptidomics].

Peptidomics was employed to systematically analyze the characteristic peptides in Galli Gigerii Endothelium Corneum and its adulterants and establish a method for distinguishing Galli Gigerii Endothelium Corneum from its adulterants, including the gizzard membranes from ducks, geese, and pigeons. UPLC-Q-Exactive Orbitrap-MS was combined with multivariate statistical analysis to analyze the peptides in Galli Gigerii Endothelium Corneum and its adulterants. The structures of peptides were identified by pNovo combined with manual recognition of spectra, and synthetic peptide standards were used for validation. LC-MS/MS was used to optimize the sample pre-processing conditions, including the extraction procedure, extraction time, extraction solvents, and solvent volumes, for the characteristic peptide LESY in Galli Gigerii Endothelium Corneum. Multiple reaction monitoring(MRM) in the ESI~+ mode with m/z 511.24→269.11 and 511.24→243.13 as detection ions was employed for qualitative and quantitative analyses. The established UPLC-MS/MS method demonstrated good specificity, stability, and durability. The content of LESY in 16 batches of Galli Gigerii Endothelium Corneum samples ranged from 55.03 to 113.36 µg·g~(-1). Additionally, a qualitative detection method for the common peptide RDPVLVSR in adulterants was established with m/z 471.28→785.45 and 471.28→670.41 as the detection ions. This study established a convenient, rapid, and accurate detection method for the characteristic peptides in Galli Gigerii Endothelium Corneum and its adulterants. The method possesses good specificity, stability, and durability, providing a valuable reference for the identification and quality control of Galli Gigerii Endothelium Corneum and other traditional Chinese medicines derived from animal sources.

Dysbiotic alteration in the fecal microbiota of patients with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common disease associated with high androgen and infertility. The gut microbiota plays an important role in metabolic diseases including obesity, hyperglycemia, and fatty liver. Although the gut microbiota has been associated with PCOS, little is known about the gut microbial structure and function in individuals with PCOS from Northeast China. In this study, 17 PCOS individuals and 17 age-matched healthy individuals were recruited for community structure and function analysis of the gut microbiota. The results showed that PCOS individuals have reduced diversity and richness of the gut microbiota compared with healthy individuals. Beta diversity analysis showed that the community structure of the gut microbiota of individuals with PCOS was significantly separated from healthy individuals. At the phylum level, PCOS individuals have reduced Firmicutes and Bacteroidota and increased Actinobacteriota and Proteobacteria compared with healthy individuals. At the family and genus levels, the composition of the gut microbiota between PCOS patients and healthy individuals was also significantly different. In addition, PICRUSt2 showed that individuals with PCOS have different microbial functions in the gut compared with healthy individuals. We finally confirmed that Bifidobacterium was enriched in the fecal samples of PCOS patients, while other 11 genera including Bacteroides, UCG_002, Eubacterium__coprostanoligenes_group_unclassified, Dialister, Firmicutes_unclassified, Ruminococcus, Alistipes, Christensenellaceae_R_7_group, Clostridia_UCG_014_unclassified, Roseburia, and Lachnospiraceae_unclassified were depleted compared with healthy individuals. These results indicate that individuals with PCOS have altered community structure and functions of the gut microbiota, which suggests that targeting the gut microbiota might be a potential strategy for PCOS intervention. IMPORTANCE: Gut microbiota plays a critical role in the development of PCOS. There is a complex and close interaction between PCOS and gut microbiota. The relationship between the pathogenesis and pathophysiological processes of PCOS and the structure and function of the gut microbiota needs further investigation.

Construction and analysis of competitive endogenous RNA networks and prognostic models associated with ovarian cancer based on the exoRBase database.

OBJECTIVE: To construct a competitive endogenous RNA (ceRNA) regulatory network in blood exosomes of patients with ovarian cancer (OC) using bioinformatics and explore its pathogenesis. METHODS: The exoRbase2.0 database was used to download blood exosome gene sequencing data from patients OC and normal controls and the expression profiles of exosomal mRNA, long non-coding RNA (lncRNA), and circular RNA (circRNA) were detected independently using R language for differential expression analysis. TargetScan and miRanda databases were combined for the prediction and differential expression of mRNA-binding microRNAs (miRNA). The miRcode and starBase databases were used to predict miRNAs that bind to differentially expressed lncRNAs and circRNAs repectively. The relevant mRNA, circRNA, lncRNA and their corresponding miRNA prediction data were imported into Cytoscape software for visualization of the ceRNA network. The R language and KEGG Orthology-based Annotation System (KOBAS) were used to execute and illustrate the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Hub genes were identified using The CytoHubba plugin. RESULTS: Thirty-one differentially expressed mRNAs, 17 differentially expressed lncRNAs, and 24 differentially expressed circRNAs were screened. Cytoscape software was used to construct the ceRNA network with nine mRNA nodes, two lncRNA nodes, eight circRNA nodes, and 51 miRNA nodes. Both GO and KEGG were focused on the Spliceosome pathway, indicating that spliceosomes are closely linked with the development of OC, while heterogenous nuclear ribonucleoprotein K and RNA binding motif protein X-linked genes were the top 10 score Hub genes screened by Cytoscape software, including two lncRNAs, four mRNAs, and four circRNAs. In patients with OC, the expression of eukaryotic translation initiation factor 4 gamma 2 (EIF4G2), SERPINE 1 mRNA binding protein 1 (SERBP1), ribosomal protein L15 (RPL15) and human leukocyte antigen complex P5 (HCP5) was significantly higher whereas that of testis expressed transcript, Y-linked 15 and DEAD-box helicase 3 Y-linked genes was lower compared to normal controls Immunocorrelation scores revealed that SERBP1 was significantly and negatively correlated with endothelial cells and CD4+ T cells and positively correlated with natural killer (NK) cells and macrophages, respectively; RPL15 was significantly positively correlated with macrophages and endothelial cells and negatively correlated with CD8+ T cells and uncharacterized cells, respectively. EIF4G2 was significantly and negatively correlated with endothelial cells and CD4+ T cells, and positively correlated with uncharacterized cells, respectively. Based on the survival data and the significant correlation characteristics derived from the multifactorial Cox analysis (P < 0.05), the survival prediction curves demonstrated that the prognostic factors associated with 3-year survival in patients with OC were The prognostic factors associated with survival were Macrophage, RPL15. CONCLUSION: This study successfully constructs a ceRNA regulatory network in blood exosomes of OV patients, which provides the specific targets for diagnosis and treatment of OC.

[Clinical study of constructing nomogram model based on multi-dimensional clinical indicators to predict prognosis of knee osteoarthritis].

OBJECTIVE: To analyze the factors affecting the prognosis of patients with knee osteoarthritis, and to construct a nomogram prediction model in conjunction with multi-dimensional clinical indicators. METHODS: The clinical data of 234 patients with knee osteoarthritis who were treated in our hospital from January 2015 to June 2021 were retrospectively analyzed, including 126 males and 108 females；age more than 60 years old for 135 cases, age less than 60 years old for 99 cases. Lysholm knee function score was used to evaluate the prognosis of the patients, and the patients were divided into good prognosis group for 155 patients and poor prognosis group for 79 patients according to the prognosis. The clinical data of the subjects in the experimental cohort were analyzed by single factor and multiple factors. The patients were divided into experimental cohort and verification cohort, the results of the multiple factor analysis were visualized to obtain a nomogram prediction model, the receiver operating characteristic curve（ROC）, calibration curve and decision curve were used to evaluate the model's discrimination, accuracy and clinical benefit rate. RESULTS: The results of multivariate analysis showed that smoking, pre-treatment K-L grades of Ⅲ to Ⅳ, and high levels of interleukin 6 （IL-6） and matrix metallo proteinase-3 （MMP-3） were risk factors for the prognosis of patients with knee osteoarthritis. ROC test results showed that the area under the curve of the nomogram model in the experimental cohort and validation cohort was 0.806[95%CI（0.742, 0.866）] and 0.786[（95%CI（0.678, 0.893）], respectively. The results of the calibration curve showed that the Brier values of the experimental cohort and verification cohort were 0.151 points and 0.134 points, respectively. When the threshold probability value in the decision curve was set to 31%, the clinical benefit rates of the experimental cohort and validation cohort were 51% and 56%, respectively. CONCLUSION: The prognostic model of patients with knee osteoarthritis constructed based on multi-dimensional clinical data has both theoretical and practical significance, and can provide a reference for taking targeted measures to improve the prognosis of patients.

Incidence and risk factors of stress urinary incontinence after laparoscopic hysterectomy.

OBJECTIVE: To observe the long-term effects of total hysterectomy on urinary function, evaluate the effects of preoperative nutritional status, urinary occult infection, and surgical factors on the induction of postoperative stress urinary incontinence (SUI), and explore the incidence and risk factors of SUI. STUDY DESIGN: From January 2017 to December 2017, 164 patients with benign non-prolapsing diseases who underwent a laparoscopic total hysterectomy in the First People's Hospital of Taicang were selected as the analysis objects. The International Incontinence Standard Questionnaire for Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) and Pelvic Floor Impact Questionnaire-short version 20 (PFDI-20) were used for telephone follow-up to subjectively assess the urinary function of patients, collect their medical records, and statistically analyze the number of postoperative SUI cases. Logistic multivariate analysis was used to analyze the influencing factors of postoperative female SUI, presented as adjusted odds ratios with 95% confidence intervals. RESULTS: Only 97 out of 164 patients completed the ICIQ-FLUTS and PFDI-20 questionnaires. Among these participants, 28 patients (28.86%) were diagnosed with SUI (study group), while 69 patients (71.13%) were classified as women without SUI (control group). The age, menopause, parity ≥ 2 times, Body mass index (BMI) ≥ 28 kg/m2, neonatal weight ≥ 4000 g, history of chronic cough, preoperative hemoglobin ≤ 100 g/L, preoperative urine bacteria ≥ 100u/L, preoperative uterine volume ≥ 90 cm3, intraoperative blood loss, and operation time of the study group were compared with those of the control group. The differences were statistically significant (P < 0.05). Further Logistic multivariate analysis showed that menopause, preoperative hemoglobin ≤ 100 g/L, preoperative urine bacteria ≥ 100u/L, uterine volume ≥ 90 cm3, history of chronic cough, BMI ≥ 28 kg/m2 were risk factors for postoperative SUI in patients undergoing hysterectomy (P < 0.05). CONCLUSIONS: Hysterectomy for benign non-prolapse diseases has a long-term potential impact on the urinary system of patients, and the risk of postoperative SUI increases. The main risk factors of SUI are parity, menopausal status, obesity, preoperative nutritional status, and occult infection of the urinary system.

The CDK4/6 Inhibitor Palbociclib Induces Cell Senescence of High-grade Serous Ovarian Cancer Through Acetylation of p53.

Cell senescence is an anti-cancer strategy following DNA repair and apoptosis, which is associated with the initiation, progression, and treatment of ovarian cancer. The CDK4/6 inhibitor alters cell cycle and induces cell senescence dependent on retinoblastoma (RB) family proteins. Objective Herein, we aimed to explore the effects of Palbociclib (a CDK4/6 inhibitor) on cellular senescence of high-grade serous ovarian cancer (HGSOC). Cell viability and cell cycle were evaluated by cell counting kit-8 and flow cytometry. Cell senescence was analyzed using the SA-ß-gal staining assay. The senescence-associated secretory phenotype was assessed using quantitative PCR (qPCR). Senescence-related markers were tested using western blot. The role of Palbociclib in vivo was clarified using xenograft tumor. Acetylation of p53 was evaluated by qPCR and western blot. The results showed that Palbociclib inhibited cell viability, blocked cell cycle at G0/G1 phase, and induced cell senescence. A rescue study indicated that knockdown of p53 reversed the effects on cell cycle and senescence induced by Palbociclib. Moreover, we found that Palbociclib promotes P300-mediated p53 acetylation, thus increasing p53 stability and transcription activity. Moreover, Palbociclib suppressed tumor growth in vivo with increased p53 and acetylated p53 levels. In conclusion, Palbociclib induced cell senescence of HGSOC through P300-mediated p53 acetylation, suggesting that Palbociclib may have the effect of treating HGSOC.

Sea Cucumber-Inspired Aerogel for Ultrafast Hemostasis of Open Fracture.

The symptomatic management of hemorrhagic shock complicated by open fractures is a great challenge, because it is also complicated by complex wound bleeding, bacterial infection, and bone defects. Inspired by the water absorption and cross-sectional microstructure of sea cucumbers, in this study, a new sea cucumber-like aerogel (GCG) is proposed. Its aligned porous structure and composition can stop bleeding rapidly and effectively with a blood clotting index of 3.73 ± 1.8%. More importantly, the data of in vivo hemostasis test in an amputating rat tail hemostatic model (15.69 ± 2.45 s, 26.95 ± 8.43 mg) and liver puncture bleeding model (23.77 ± 2.68 s, 36.22 ± 16.92 mg) also indicate the excellent hemostatic performance of GCG. In addition, GCG also shows a significant inhibitory effect on S. aureus and E. coli, which can prevent the occurrence of postoperative osteomyelitis. Not only that, after filling in the bone defect, it is shown that this GCG aerogel completely degrades eight weeks after surgery and induces new bone ingrowth, achieving functional regeneration after hemostasis of an open fracture defect. Generally, because of its combination of hemostatic, antibacterial, and osteogenic activities, this new aerogel is a promising option for open fractures treatment.

Citral protects against LPS-induced endometritis by inhibiting ferroptosis through activating Nrf2 signaling pathway.

INTRODUCTION: Endometritis is the inflammatory condition of the uterus. Citral, a component of lemongrass oil, is known to exhibit anti-inflammatory activity. AIM: The effects of citral on LPS-induced endometritis were tested and the mechanisms were investigated. METHODS: LPS-induced endometritis mice model was established and the effects of citral were detected using this model. Inflammatory cytokines were tested by ELISA. Ferroptosis was assessed by detecting GSH, ATP, MDA, and Fe2+ levels. Signaling pathway was tested by western blot analysis. RESULTS: Citral prevented LPS-induced endometritis through attenuating uterine pathological changes and inflammatory cytokine release. Meanwhile, citral prevents LPS-induced ferroptosis through attenuating MDA and Fe2+ levels, as well as increasing ATP and GSH levels. Furthermore, citral up-regulated Nrf2 and HO-1 expression and attenuated NF-κB activation. In addition, in Nrf2 knockdown mice, the inhibitory roles of citral on ferroptosis and endometritis were largely reversed. CONCLUSION: Taken together, citral inhibited LPS-induced endometritis through preventing ferroptosis, which were regulated by Nrf2 signaling pathway.

Gut microbiota dysbiosis in polycystic ovary syndrome: Mechanisms of progression and clinical applications.

Polycystic ovary syndrome (PCOS) is the most common endocrine diseases in women of childbearing age that leads to menstrual disorders and infertility. The pathogenesis of PCOS is complex and has not yet been fully clarified. Gut microbiota is associated with disorders of lipid, glucose, and steroid hormone metabolish. A large body of studies demonstrated that gut microbiota could regulate the synthesis and secretion of insulin, and affect androgen metabolism and follicle development, providing us a novel idea for unravelling the pathogenesis of PCOS. The relationship between gut microbiota and the pathogenesis of PCOS is particularly important. This study reviewed recent research advances in the roles of gut microbiota in the occurrence and development of PCOS. It is expected to provide a new direction for the treatment of PCOS based on gut microbiota.

Malignancies in systemic rheumatic diseases: A mini review.

There is an increased risk of malignancies in patients with many systemic rheumatic diseases, which negatively impact on their quality of life. The risk and types of malignancies can differ by the type of rheumatic diseases. Possible mechanisms linking them are dynamic and complicated, including chronic inflammation and damage in rheumatic disease, inability to clear oncogenic infections, shared etiology and some anti-rheumatic therapies. Although certain disease-modifying anti-rheumatic drugs (DMARDs) have been proved to be potentially carcinogenic, the majority of them were not associated with increased risk of most malignancies in patients with systemic rheumatic diseases.

Deoxycholic acid inhibits Staphylococcus aureus-induced endometritis through regulating TGR5/PKA/NF-κB signaling pathway.

Endometritis, a common gynecological disease, is the most common cause of infertility. As a natural metabolite of gut microbiota, deoxycholic acid (DCA) has been reported to have anti-inflammatory function. In the current study, the protective role of DCA on Staphylococcus aureus (S.aureus)-induced endometritis was tested. In vivo, DCA inhibited uterine histological change, MPO activity, endometrial barrier disruption, and inflammatory cytokine production induced by S.aureus. In vitro, DCA suppressed S.aureus-induced TNF-α and IL-1ß production in mouse endometrial epithelial cells (mEECs). Also, DCA markedly suppressed S.aureus-induced NF-κB activation. Takeda G protein-coupled receptor 5 (TGR5)is a critical bile acid membranereceptor that mainly regulated the cyclic AMP (cAMP)/protein kinase A (PKA)signaling pathway to inhibit NF-κB activation. We found DCA significantly increased TGR5 and PKA expression and S.aureus-induced inflammatory cytokine production and NF-κB activation were prevented by TGR5 inhibitor and PKA inhibitor. In conclusion, DCA protected S.aureus-induced endometritis by regulating TGR5/PKA/NF-κB signaling pathway.

New Insights into the Understanding of Mechanisms of Radiation-Induced Heart Disease.

OPINION STATEMENT: Cancer patients who receive high-dose thoracic radiotherapy may develop radiation-induced heart disease (RIHD). The clinical presentation of RIHD comprises coronary artery atherosclerosis, valvular disease, pericarditis, cardiomyopathy, and conduction defects. These complications have significantly reduced due to the improved radiotherapy techniques. However, such methods still could not avoid heart radiation exposure. Furthermore, people who received relatively low-dose radiation exposures have exhibited significantly elevated RIHD risks in cohort studies of atomic bomb survivors and occupational exposures. The increased potential in exposure to natural and artificial ionizing radiation sources has emphasized the necessity to understand the development of RIHD. The pathological processes of RIHD include endothelial dysfunction, inflammation, fibrosis, and hypertrophy. The underlying mechanisms may involve the changes in oxidative stress, DNA damage response, telomere erosion, mitochondrial dysfunction, epigenetic regulation, circulation factors, protein post-translational modification, and metabolites. This review will discuss the recent advances in the mechanisms of RIHD at cellular and molecular levels.

Identification of a ferroptosis-related long noncoding RNA signature with a prognostic value in adrenocortical carcinoma.

Background: Adrenocortical carcinoma (ACC) is an uncommon endocrine malignancy associated with poor clinical outcome. As a novel form of cell death, ferroptosis is reliant on the accumulation of iron and reactive oxygen species and is involved in the pathogenesis of various tumors, including ACC. Our study aimed to identify and characterize the prognostic ferroptosis-related lncRNA signature (FerRLSig) in ACC. Methods: A regulatory network of ferroptosis-related lncRNAs (FerRLs) and mRNAs was constructed based on The Cancer Genome Atlas (TCGA). Univariate and multivariate Cox regression assays were performed to construct the FerRLSig. Results: Twenty-four FerRLs were identified in the prognostic model, and the high-risk FerRLSig was related to the worse overall survival (OS) in ACC [hazard ratio (HR): 1.936 (1.484-2.526), p < 0.001]. The area under the curve (AUC) value of the FerRLSig was 0.936 according to the receiver operating characteristic (ROC) analyses, superior to other traditional clinicopathological features, further supported the utility in prognosis prediction of ACC. We further established a prognostic nomogram combining clinical factors with the FerRLSig, which showed favorable efficacy for survival prediction. Next, gene set enrichment analysis (GSEA) revealed that gene sets were involved in many immune regulatory biological processes related to malignancies. T-cell function of type II INF response and the immune checkpoints, including CD40, CD276, IDO2, NRP1, and CD80, were expressed with a significant difference between the low- and high-risk groups. Conclusion: This study offered new insights into the pathogenesis of ACC. The novel FerRLSig could be useful in predicting survival and may provide information of immunological research and treatment for ACC patients.

Early myocardial injury and coagulation activation in thoracoscopic left atrial appendage clipping.

BACKGROUND: Thoracoscopic left atrial appendage clipping as a new strategy for stroke prevention. This study was established to observe the changes in myocardial injury and coagulation during the perioperative to provide the basis for anticoagulation strategy. METHODS: Fifty-two patients with nonvalvular atrial fibrillation who completed thoracoscopic left atrial appendage clipping alone and 52 matched controls with thoracoscopic lobectomy were included in the study. The changes in coagulation and myocardial enzyme during the perioperative period were compared by t-test or nonparametric test. Linear correlation analysis was performed on the trend changes of each indicator in the left atrial appendage clipping group. RESULTS: Compared with the control group, the postoperative cardiac troponin I level in the thoracoscopic left atrial appendage clip group was significantly higher than that before the operation; there was no significant difference in the increase of myoglobin between the two groups. In the coagulation function, there was no significant difference in the increase of fibrinogen between the two groups. Postoperative D-dimer and fibrin degradation products were significantly increased, especially the left atrial appendage clip group was significantly higher than the control group, and even showed a trend of secondary increase. Cardiac troponin I was positively correlated with C-reactive protein, fibrinogen and von Willebrand Factor activity, and the Spearman nonparametric correlation coefficients were 1, 0.829, and 0.829, respectively (all p < .05). CONCLUSION: Thoracoscopic left atrial appendage closure surgery presents early myocardial injury and activation of coagulation function. The secondary increase of coagulation index needs our attention.

Stroke prevention of thoracoscopic left atrial appendage clipping in patients with non-valvular atrial fibrillation at high risk of stroke and bleeding: study protocol for a non-randomised controlled clinical trial.

INTRODUCTION: Non-valvular atrial fibrillation (NVAF) is a high-risk factor for ischaemic stroke. The 2016 European Society of Cardiology Atrial Fibrillation Management guidelines recommend oral anticoagulants (OACs) to prevent stroke in men with CHA2DS2-VASc scores ≥2 and women ≥3. However, in patients with a high risk of stroke and a high risk of bleeding (HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly (> 65 years), Drugs/alcohol concomitantly) score≥3), OAC had a higher risk of bleeding. Left atrial appendage closure (LAAC) is non-inferior to OAC as a means of preventing stroke in several studies. As a minimally invasive intervention to prevent stroke, transthoracic LAAC (TS-LAAC) has a high successful closure rate, but there is a lack of literature reports directly comparing it with OAC. Our research compares TS-LAAC with novel oral anticoagulants (NOACs) and provides an appropriate programme for stroke prevention in a specific population. METHODS AND ANALYSIS: This is a non-randomised controlled trial study protocol, and we will conduct this study from April 2022 to April 2025. The study included 186 patients with confirmed NVAF, 93 of whom completed thoracoscopic LAAC, and the control group treated with NOACs. The primary outcome was the incidence of stroke and systemic embolism, as well as the composite endpoint events (stroke, systemic embolism, myocardial infarction, bleeding, cardiovascular death, etc). Secondary outcomes were ischaemic stroke, haemorrhagic stroke, any bleeding events, death from cardiovascular causes, death from all causes, residual root rate in the surgery group, device-related thrombosis in the surgery group, changes in blood pressure, cardiac chamber size changes, etc. Each subject completed at least 1 year of follow-up. ETHICS AND DISSEMINATION: The study has been approved by the Medical Ethics Committee of Beijing Tiantan Hospital, Capital Medical University, China (approval number: KY2022-013-02). The results from this study will be disseminated through manuscript publications and national/international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2200058109.

Identification of Novel Hypoxia Subtypes for Prognosis Based on Machine Learning Algorithms.

Objective: A reduced level or tension or the deprivation of oxygen is termed hypoxia. It is common for tumours to outgrow their natural source of nutrients, which causes hypoxia in some tumour regions. Hypoxia affects ovarian cancer (OC) in several ways. Methods: In this study, the expression patterns of prognostic hypoxia-related genes were curated, and consensus clustering analyses were performed to determine hypoxia subtypes in OC included in The Cancer Genome Atlas cohort. Two hypoxia-related subtypes were observed and considered for further investigation. The analyses of differentially expressed genes (DEGs), gene ontology, mutation, and immune cell infraction were performed to explore the underlying molecular mechanisms. Results: In total, 377 patients with OC were classified into two subgroups based on the subtype of hypoxia. The clinical outcome was considerably poor for patients with hypoxia subtype 2. DEG and protein-protein interaction analyses revealed that the expression levels of CLIP2 and SH3PXD2A were low in OC tissues. Immune cell infarction analysis revealed that the subtypes were associated with the tumour microenvironment (TME). Conclusion: Our findings established the existence of two distinctive, complex, and varied hypoxia subtypes in OC. Findings from the quantitative analysis of hypoxia subtypes in patients improved our understanding of the characteristics of the TME and may facilitate the development of more efficient treatment regimens.