Thin-Film Buckling Theory and Clinical Application of the Mechanism of Double Eyelid Formation.

BACKGROUND: The mechanism underlying the formation of upper eyelid creases has been the subject of extensive study and ongoing debate. This research aims to elucidate the principles of upper eyelid creases formation, leveraging the membrane bending theory from engineering mechanics. METHODS: We developed an anatomical model of the eyelid and implemented the finite element analysis. Preprocessing and mesh division were conducted using HyperMesh, followed by computational analysis with Abaqus. This approach enabled the observation of dynamic changes in the upper eyelid during eye opening and closing. RESULTS: The study reveals that natural upper eyelid crease formation is influenced by multiple factors. These include the softer texture of the upper eyelid skin and the suborbicularis oculi fat, reduced rigidity at the eyelid crease, optimal contraction force of the upper eyelid, and the strategic placement of the pre-tarsal fat pad just above the eyelid crease. CONCLUSIONS: Ultimately, our findings demonstrate the effectiveness of finite element analysis, grounded in membrane bending theory, in elucidating the dynamics of upper eyelid crease formation. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .

Identification of novel prognostic risk signature of breast cancer based on ferroptosis-related genes.

Ferroptosis is a type of cell regulated necrosis triggered by intracellular phospholipid peroxidation, which is more immunogenic than apoptosis. Therefore, genes controlling ferroptosis may be promising candidate biomarkers for tumor therapy. In this study, we investigate the function of genes associated with ferroptosis in breast cancer (BC) and systematically evaluate the relationship between ferroptosis-related gene expression and prognosis of BC patients from the Cancer Genome Atlas database. By using the consensus clustering method, 1203 breast cancer samples were clustered into two clearly divided subgroups based on the expression of 237 ferroptosis-related genes. Then differentially expressed analysis and least absolute shrinkage and selection operator were used to identify the prognosis-related genes. Furthermore, the genetic risk signature was constructed using the expression of prognosis-related genes. Our results showed that the genetic risk signature can identify patient subgroups with distinct prognosis in either training cohort or validation, and the genetic risk signature was associated with the tumor immune microenvironment. Finally, the Cox regression analysis indicated that our risk signature was an independent prognostic factor for BC patients and this signature was verified by the polymerase chain reaction and western blot. Within this study, we identified a novel prognostic classifier based on five ferroptosis-related genes which may provide a new reference for the treatment of BRCA patients.

Development and Validation of a Prognostic Classifier Based on Lipid Metabolism-Related Genes for Breast Cancer.

Background: The changes of lipid metabolism have been implicated in the development of many tumors, but its role in breast invasive carcinoma (BRCA) remains to be fully established. Here, we attempted to ascertain the prognostic value of lipid metabolism-related genes in BRCA. Methods: We obtained RNA expression data and clinical information for BRCA and normal samples from public databases and downloaded a lipid metabolism-related gene set. Ingenuity Pathway Analysis (IPA) was applied to identify the potential pathways and functions of Differentially Expressed Genes (DEGs) related to lipid metabolism. Subsequently, univariate and multivariate Cox regression analyses were utilized to construct the prognostic gene signature. Functional enrichment analysis of prognostic genes was achieved by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Kaplan-Meier analysis, Receiver Operating Characteristic (ROC) curves, clinical follow-up results were employed to assess the prognostic potency. Potential compounds targeting prognostic genes were screened by Connectivity Map (CMap) database and a prognostic gene-drug interaction network was constructed using Comparative Toxicogenomics Database (CTD). Furthermore, we separately validated the selected marker genes in BRCA samples and human breast cancer cell lines (MCF-7, MDA-MB-231). Results: IPA and functional enrichment analysis demonstrated that the 162 lipid metabolism-related DEGs we obtained were involved in many lipid metabolism and BRCA pathological signatures. The prognostic classifier we constructed comprising SDC1 and SORBS1 can serve as an independent prognostic marker for BRCA. CMap filtered 37 potential compounds against prognostic genes, of which 16 compounds could target both two prognostic genes were identified by CTD. The functions of the two prognostic genes in breast cancer cells were verified by cell function experiments. Conclusion: Within this study, we identified a novel prognostic classifier based on two lipid metabolism-related genes: SDC1 and SORBS1. This result highlighted a new perspective on the metabolic exploration of BRCA.

Screening of DNA Damage Repair Genes Involved in the Prognosis of Triple-Negative Breast Cancer Patients Based on Bioinformatics.

Background: Triple-negative breast cancer (TNBC) is a special subtype of breast cancer with poor prognosis. DNA damage response (DDR) is one of the hallmarks of this cancer. However, the association of DDR genes with the prognosis of TNBC is still unclear. Methods: We identified differentially expressed genes (DEGs) between normal and TNBC samples from The Cancer Genome Atlas (TCGA). DDR genes were obtained from the Molecular Signatures Database through six DDR gene sets. After the expression of six differential genes were verified by quantitative real-time polymerase chain reaction (qRT-PCR), we then overlapped the DEGs with DDR genes. Based on univariate and LASSO Cox regression analyses, a prognostic model was constructed to predict overall survival (OS). Kaplan-Meier analysis and receiver operating characteristic curve were used to assess the performance of the prognostic model. Cox regression analysis was applied to identify independent prognostic factors in TNBC. The Human Protein Atlas was used to study the immunohistochemical data of six DEGs. The prognostic model was validated using an independent dataset. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analysis were performed by using gene set enrichment analysis (GSEA). Single-sample gene set enrichment analysis was employed to estimate immune cells related to this prognostic model. Finally, we constructed a transcriptional factor (TF) network and a competing endogenous RNA regulatory network. Results: Twenty-three differentially expressed DDR genes were detected between TNBC and normal samples. The six-gene prognostic model we developed was shown to be related to OS in TNBC using univariate and LASSO Cox regression analyses. All the six DEGs were identified as significantly up-regulated in the tumor samples compared to the normal samples in qRT-PCR. The GSEA analysis indicated that the genes in the high-risk group were mainly correlated with leukocyte migration, cytokine interaction, oxidative phosphorylation, autoimmune diseases, and coagulation cascade. The mutation data revealed the mutated genes were different. The gene-TF regulatory network showed that Replication Factor C subunit 4 occupied the dominant position. Conclusion: We identified six gene markers related to DDR, which can predict prognosis and serve as an independent biomarker for TNBC patients.

Cannabinoid receptor agonist WIN55212-2 reduces unpredictable mild stress-induced depressive behavior of rats.

BACKGROUND: Depression is a neurological disorder characterized by persistent low mood. A number of studies have suggested that the use of type 1 cannabinoid receptor (CB1R) agonists can reduce depressive behavior, but its effect on the depressive behavior and nerve damage of rats exposed to chronic unpredictable mild stress (CUMS) has not been reported. METHODS: Rats were exposed to CUMS for 4 weeks to induce depressive behavior. Male Sprague-Dawley (SD) rats aged 6-8 weeks were randomly divided into six groups: control group (control), depression group (CUMS), depression + fluoxetine group (Flu), depression + WIN55212-2 group (WIN), depression + NF-κB inhibitor group (PDTC), and depression + WIN + PDTC group (WIN + PDTC). We performed four behavioral experiments test to evaluate the depressive behaviors of rats. Hematoxylin and eosin (HE) and Nissl staining were performed to observe the neuron structures of the hippocampus. Enzyme-linked immunosorbent assay (ELISA) was used to measure the concentrations of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 (COX-2). Biochemical experiments were performed to evaluate the concentrations of nitric oxide (NO), malondialdehyde (MDA), reactive oxygen species (ROS), and superoxide dismutase (SOD). Fluorescence quantitative PCR was used to detect the mRNA expression of brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB), and inducible nitric oxide synthase (iNOS) in the hippocampus, and western blot was performed to detect protein expression levels related to the NF-κB signaling pathway in the hippocampus. RESULTS: Compared with the normal control group, CUMS significantly induced abnormal behaviors in stressed rats. The concentrations of pro-inflammatory factors and oxidative stress injury factors in the hippocampus of the CUMS group increased significantly. The interventions of Flu, WIN, and PDTC significantly reduced neuroinflammation and oxidative stress injury. Compared with the WIN group, the WIN + PDTC intervention group had better results. In addition, WIN could significantly inhibit the activation of the NF-κB signaling pathway. CONCLUSIONS: This study showed that cannabinoid receptor agonists can reduce the CUMS-induced depressive behaviors of rats by blocking the NF-κB signaling pathway to alleviate neuroinflammation and oxidative stress injury.

Exchange proteins directly activated by cyclic adenosine monophosphate inhibitor reverses mechanical allodynia via the modification of astrocytes activity in the spinal cord.

BACKGROUND: Gliosis and inflammation are pivotal in the development of acute and chronic pain. Here, we demonstrated a previously unidentified molecular mechanism in which the activation of exchange proteins directly activated by cyclic adenosine monophosphate (Epac)1 accelerated the activation of astrocytes in the spinal cord, thereby promoting chronic postsurgical pain (CPSP). METHODS: We established a rat model of CPSP induced by skin/muscle incision and retraction (SMIR). Pain behaviors were assessed using mechanical withdrawal threshold (MWT) at different times. The lumbosacral enlargement of the spinal cord was isolated to detect the expression of Epac1 and the activity of astrocytes. They were assessed using western blot and immunofluorescence staining. RESULTS: SMIR induced persistent mechanical hyperalgesia after surgery. This hyperalgesia response was prolonged to more than 21 d after surgery. The time course of spinal Epac1 upregulation was correlated with SMIR-induced pain behaviors. Meanwhile, Epac1 immunoreactivity was colocalized primarily with astrocytes but not with microglial cells or neurons on 7 d after surgery. Intrathecal injection of Epac1 inhibitor CE3F4 significantly suppressed SMIR-induced mechanical allodynia and activation of astrocytes in the spinal cord. This analgesic effect of single-dose administration of CE3F4 lasted up to 6 h and wore off at 12 h after injection. CONCLUSIONS: Spinal Epac1-mediated activation of astrocytes may facilitate CPSP. Inhibition of Epac1 may effectively prevent CPSP.

Case Report: Significant Efficacy of Pyrotinib in the Treatment of Extensive Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Cutaneous Metastases: A Report of Five Cases.

BACKGROUND: Breast cancer (BC) is the most common tumor to develop cutaneous metastases. Most BCs with cutaneous metastasis are human epidermal growth factor receptor 2 (HER2)-positive subtypes. Although the molecular mechanisms of breast cancer metastasis to different sites and the corresponding treatment methods are areas of in-depth research, there are few studies on cutaneous metastasis. CASE PRESENTATION: Five HER2-positive BC patients with extensive cutaneous metastases were treated with a regimen containing pyrotinib, a novel small-molecule tyrosine kinase inhibitor that irreversibly blocks epidermal growth factor receptor (EGFR), HER2, and human epidermal growth factor receptor 4 (HER4), then their cutaneous metastases quickly resolved at an astonishing speed and their condition was well controlled during the follow-up period. CONCLUSIONS: This case series reports the significant therapeutic effect of pyrotinib on cutaneous metastases of HER2-positive BC for the first time. Based on this, we recommend that pyrotinib can be used as a supplement to trastuzumab for HER2-positive BC patients with cutaneous metastases. In addition, we should consider that the pan-inhibitory effect of pyrotinib on EGFR, HER2, and HER4 may provide a dual therapeutic effect against HER2 and mucin 1.

Perioperative Analgesic Effects of Preemptive Ultrasound-Guided Rectus Sheath Block Combined with Butorphanol or Sufentanil for Single-Incision Laparoscopic Cholecystectomy: A Prospective, Randomized, Clinical Trial.

PURPOSE: Pain after single-incision laparoscopic cholecystectomy (SILC), especially visceral pain, often troubles patients and doctors. Whether preemptive butorphanol can relieve visceral pain in patients undergoing SILC remains unknown. The goal of this study was to assess the efficacy of ultrasound-guided bilateral rectus sheath block (RSB) and butorphanol for perioperative analgesia in patients undergoing SILC. PATIENTS AND METHODS: Fifty-eight patients who met the criteria were randomly divided into two groups, both of which were given preemptive RSB. Patients were given either butorphanol 0.02mg/kg (group B, n=29) or sufentanil 0.1 µg/kg (group S, n=29) as preemptive analgesia. The primary outcome was the cumulative frequency of rescue analgesic request within 24 hours after operation. Secondary outcomes were numeric rating scale (NRS) scores (from 0 to 10) of incisional pain and visceral pain, the length of hospital stay and the incidence of postoperative adverse events. RESULTS: The frequency of postoperative rescue analgesic request of group S was significantly higher than that of group B (P=0.021). The NRS scores for visceral pain were lower in group B at 2, 6 and 12 hours after surgery than in group S (both P<0.001). The occurrence of postoperative nausea and vomiting (PONV) was significantly higher in group S. There were no significant differences between two groups for other outcomes. CONCLUSION: Butorphanol can provide sufficient visceral pain treatment after SILC than the dose of sufentanil in equal analgesic effect.

Long Non-Coding RNA HULC Promotes the Development of Breast Cancer Through Regulating LYPD1 Expression by Sponging miR-6754-5p.

INTRODUCTION: Long non-coding RNAs (lncRNAs) were found to regulate many biological processes including cancer development, immunology and other diseases. LncRNA HULC was found to be oncogenes in many cancer progression. However, the role of HULC in the regulation of breast cancer remains unclear. METHODS: The expression of HULC and miR-6754-5p was examined by RT-PCR. Through knockdown of HULC, we found that the proliferation abilities coupled with migration and invasion abilities were significantly decreased. And also, we verified that overexpression of miR-6754-5p significantly decreased the proliferation ability of breast cancer cells. RESULTS: In this study, we found that lncRNA HULC was overexpressed in breast cancer tissues and cell lines compared to normal healthy breast tissues and normal breast cell line. Moreover, the high expression of HULC was associated with metastasis and malignancy of breast cancers. Mechanically, we found that HULC can bind to miR-6754-5p directly through complementary base pairing. Furthermore, we found that HULC regulates the expression of LYPD1 through sponging miR-6754-5p. Moreover, overexpression of LYPD1 can rescue the migration and invasion abilities of breast cancer cells decreased by knockdown of HULC or overexpression of miR-6754-5p. CONCLUSION: Our study showed the role of HULC in promoting breast cancer development and explained the detailed molecular mechanisms.