MEF2C Alleviates Postoperative Cognitive Dysfunction by Repressing Ferroptosis.

BACKGROUND: Ferroptosis, a form of programmed cell death featured by lipid peroxidation, has been proposed as a potential etiology for postoperative cognitive dysfunction (POCD). Myocyte-specific enhancer factor 2C (MEF2C), a transcription factor expressed in various brain cell types, has been implicated in cognitive disorders. This study sought to ascertain whether MEF2C governs postoperative cognitive capacity by affecting ferroptosis. METHODS: Transcriptomic analysis of public data was used to identify MEF2C as a candidate differentially expressed gene in the hippocampus of POCD mice. The POCD mouse model was established via aseptic laparotomy under isoflurane anesthesia after treatment with recombinant adeno-associated virus 9 (AAV9)-mediated overexpression of MEF2C and/or the glutathione peroxidase 4 (GPX4) inhibitor RSL3. Cognitive performance, Nissl staining, and ferroptosis-related parameters were assessed. Dual-luciferase reporter gene assays and chromatin immunoprecipitation assays were implemented to elucidate the mechanism by which MEF2C transcriptionally activates GPX4. RESULTS: MEF2C mRNA and protein levels decreased in the mouse hippocampus following anesthesia and surgery. MEF2C overexpression ameliorated postoperative memory decline, hindered lipid peroxidation and iron accumulation, and enhanced antioxidant capacity, which were reversed by RSL3. Additionally, MEF2C was found to directly bind to the Gpx4 promoter and activate its transcription. CONCLUSIONS: Our findings suggest that MEF2C may be a promising therapeutic target for POCD through its negative modulation of ferroptosis.

Phagocytosis-Regulators-Based Signature to Predict the Prognosis and Chemotherapy Resistance for Breast Cancer Patients.

Phagocytosis is crucial in tumor surveillance and immune function. The association between phagocytosis and the outcomes of breast cancer patients has not been well-determined. In this study, data were downloaded from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) databases to investigate the role of phagocytosis in breast cancer. Data from the TCGA and GEO databases were used to investigate the prognostic role of phagocytosis in breast cancer. Then, we performed pathway enrichment analysis, copy number variation (CNV) and single-nucleotide variant (SNV) analyses, immune infiltration analysis, calculation of tumor purity, stromal score, and immune score, and consistent clustering. We also constructed a phagocytosis-regulators-based signature system to examine its association in survival and drug response. The genomic and expression differences in the phagocytosis regulators in breast cancer were systematically analyzed, explaining the widespread dysregulation of phagocytosis regulators. Using the investigated association of phagocytosis regulators with the prognosis and tumor immune environment, we constructed a prognostic model based on phagocytosis regulators. We discovered that patients with high risk scores had a poor prognosis and were negatively associated with immune functions. The model had preferential predictive performance and significantly consistent drug-resistance prediction results. Our findings suggest that the phagocytosis-factors-based scoring system can be used as a novel prognostic factor, serving as a powerful reference tool for predicting prognosis and developing methods against drug resistance.

Uncovering BTB and CNC Homology1 (BACH1) as a Novel Cancer Therapeutic Target.

BTB and CNC homology1 (BACH1), working as a transcriptional factor, is demonstrated to function on the regulation of epigenetic modifications by complex regulatory networks. Although BACH1 is reported as an oncogene, the overall analysis of its role remains lacking. In this study, we uncovered the capacity of BACH1 as a new pan-cancer therapeutic target. We found that BACH1 is highly expressed in abundant cancers and correlated with the poor prognosis of most cancers. The mutation sites of BACH1 varied in different cancer types and correlated to patients' prognoses. The tumor mutation burden (TMB) in four cancer species and up to six tumor infiltrated immune cells had a significant relevance with BACH1. The enrichment analysis showed that the BACH1-associated genes were significantly enriched in the pathways of PD-1/L1 expression, ubiquitin-mediated proteolysis, T cell receptor, Th17 cell differentiation. We then demonstrated that BACH1 is positively correlated with the expression of many candidate genes, incluing SRPK2, GCLM, SLC40A1, and HK2 but negatively correlated with the expression of KEAP1 and GAPDH. Overall, our data shed light on BACH1's effect on latent utility in cancer targeting therapy.

Repair of Breast Defect by Transfer of a Contralateral Internal Mammary Artery Perforator Flap.

This is a case report of a patient with a borderline phyllodes tumor in the left breast. Seventeen months after the resection of the phyllodes tumor from the patient's left breast, the tumor occurred again 5 months ago in the surgical region. A large defect was generated after the extended resection of the left breast mass, and it was repaired with a contralateral internal mammary artery perforator flap. After the operation, bilateral breast symmetry was good, and the patient was satisfied with the shape of the breast. Postoperative follow-up was performed for 15 months, and no local recurrence was observed.

[Research progress in epidemiology, diagnosis and treatment for pancreatic cancer].

Pancreatic cancer is a highly lethal disease in gastrointestinal malignant tumors. The mortality of pancreatic cancer closely parallels its incidence. Most patients with pancreatic cancer remain asymptomatic until the disease reaches an advanced stage. There is no program for screening patients at high risk of pancreatic cancer. Although CT, MRI, positron emission tomography, endoscopic ultrasonography, and endoscopic ultrasonography-guided fine-needle aspiration offer high diagnostic ability for pancreatic cancer, it cannot be found at the early stage easily. Surgical resection is regarded as the only potentially curative treatment and adjuvant chemotherapy is given after surgery. This article reviews epidemiology, risk factors, diagnosis and treatment for pancreatic cancer by summarizing relevant literature.

[Research progress of Lauren classification for gastric cancer].

Gastric cancer (GC) is one of the most common malignant tumors with high heterogeneity. According to Lauren classification, GC is divided into intestinal type and diffuse type. With rapid progress in technologies and ideas in the clinical diagnosis for GC, the normalized and individualized comprehensive treatment has become the main trend. However, the clinicopathological characteristics, remedy and prognosis for GC may be different because of the different classifications and stages.

[Laparoscopic cystogastrostomy with posterior approach for pancreatic pseudocyst drainage].

OBJECTIVE: To determine the clinical value of laparoscopic cystogastrostomy in the treatment of pancreatic pseudocyst. METHODS: Twenty-one patients with pancreatic pseudocyst received total laparoscopic cystogastrostomy. The data on intra-operative bleeding, operative time, post-operative time to get out of bed, time of first flatus/bowel motion, complication and duration of hospital stay were observed and analyzed retrospective1y. RESULTS: Twenty-one patients were successfully carried out the laparoscopic surgery. The average operation time was 90(62-120) min. The blood loss was less than 100 mL in all patients. The average time of hospital stay was 8 d. After 12-18 month follow-up, all patients recovered smoothly without any complication. CONCLUSION: Total laparoscopic cystogastrostomy with the posterior approach is a feasible, safe and minimal invasive procedure for pancreatic pseudocyst, which can be recommended to the clinical application.