Characteristics and significance of programmed cell death-related gene expression signature in skin cutaneous melanoma.

BACKGROUND: Programmed cell death (PCD) pathways play crucial roles in the pathogenesis of skin cutaneous melanoma (SKCM). Understanding their prognostic significance and clinical implications is imperative for the development of personalized treatment strategies. METHODS: A total of 1466 PCD-related genes were analyzed using data from The Cancer Genome Atlas (TCGA)-SKCM cohort (n = 353). Prognostic cell death index (CDI) was established and validated through survival analysis and predictive modeling. Functional enrichment, protein-protein interaction (PPI), consensus clustering, and tumor microenvironment assessment and drug sensitivity analysis were performed to elucidate the biological and clinical relevance of CDI. RESULTS: CDI effectively stratified SKCM patients into high and low-risk groups, demonstrating significant differences in survival outcomes. It exhibited predictive value for survival at 1, 3, and 5 years. The concordance index (C-index) was 0.794 in the training set, and 0.792 and 0.821 in the internal and external validation sets, respectively. The corresponding area under curve (AUC) was all above 0.75 in these data sets. Functional enrichment analysis revealed significant associations with immune response and inflammatory processes. PPI analysis identified key molecular modules associated with apoptosis and chemokine signaling. Consensus clustering unveiled three discernible subtypes demonstrating notable disparities in survival outcomes based on CDI expression profiles. Assessment of the tumor microenvironment highlighted correlations with immune cell infiltration such as M1 macrophages and T cells. Drug sensitivity analysis indicated tight correlations between CDI levels and response to immunotherapy. CONCLUSION: Our comprehensive analysis establishes the prognostic significance of PCD-related genes in SKCM. CDI emerges as a promising prognostic biomarker, offering insights into tumor biology and potential implications for personalized treatment strategies. Further validation and clinical integration of CDI are warranted to improve SKCM management and patient outcomes.

Effect of dexmedetomidine infusion on postoperative sleep disturbances in women with breast cancer: A monocentric randomized-controlled double-blind trial.

BACKGROUND: Most women with breast cancer are prone to postoperative sleep disturbances (POSD). Little is known about the differences between sevoflurane and propofol combined with dexmedetomidine on POSD in the same context. We investigated the effect of intra-operative sevoflurane or propofol combined with intravenous dexmedetomidine on the incidence of POSD and postoperative sleep structures. METHODS: A monocentric, randomized-controlled, double-blind trial. Female patients undergoing radical surgery for breast cancer were randomly assigned to receive sevoflurane and placebo, sevoflurane and dexmedetomidine, propofol and placebo, or propofol and dexmedetomidine. Dexmedetomidine was administered at 1.0 µg kg-1 infusion 15 min before induction, then infused at 0.4 µg kg-1 h-1 until the surgical drain started to be placed. The primary outcome was the incidence of POSD within the postoperative first three days (defined as an Athens Insomnia Scale score ≥ 6 points on at least one day of postoperative first three days). The secondary outcome was the duration of sleep structures, collected from the Fitbit Charge 2® smart bracelet (Fitbit, Inc., San Francisco, CA, USA). RESULTS: There were 188 women analyzed with the modified intention-to-treat method. The incidences of POSD in the dexmedetomidine and placebo groups were similar (p = 0.649). In the sevoflurane sedation strategy, dexmedetomidine decreased nocturnal wakefulness on postoperative first day (p = 0.001). In the propofol sedation strategy, dexmedetomidine increased nocturnal deep sleep on postoperative first (p < 0.001) and third (p < 0.001) days. CONCLUSION: Intra-operative infusion of dexmedetomidine had no significant effect on POSD but decreased nocturnal wakefulness in the sevoflurane group and increased nocturnal deep sleep in the propofol group. TRIAL REGISTRATION: Registered at www.chictr.org.cn (ChiCTR2300070136).

Antioxidant vitamins supplementation reduce endometriosis related pelvic pain in humans: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to clarify the effect of antioxidant vitamins supplementation on endometriosis-related pain. METHODS: A systematic search of PubMed, Web of Science, Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNK) databases was conducted to identify relevant studies published in English and Chinese up to 16 March 2023. The search terms used were "endometriosis" OR "endometrioma" OR "endometrium" AND "antioxidant" OR "Vitamin C" OR "Vitamin E" OR "Vitamin D" OR "25-OHD" OR "25(OH)D" OR "25-hydroxyvitamin D". Eligible studies were randomized controlled trials (RCTs) that assessed pain scores using the Visual Analogue Scale (VAS). Mean differences or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the effect of antioxidant vitamins supplementation on endometriosis. The quality of the included studies was assessed using the Cochrane Risk of Bias Tool. The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. RESULTS: A total of 13 RCTs involving 589 patients were included in this meta-analysis. We identified 11 studies that evaluated the effect of antioxidant vitamins supplementation on endometriosis-related pain. The results indicated that the supplementation of antioxidant vitamins can effectively alleviate endometriosis-related pain. Subgroup analysis showed that the supplementation of vitamin E (with or without vitamin C) had a positive effect on improving clinical pelvic pain in patients with chronic pelvic pain. Conversely, supplementation of vitamin D was associated with a reduction in pelvic pain in endometriosis patients, but the difference was not statistically significant compared to the placebo. Additionally, we observed changes in oxidative stress markers following vitamin supplementation. Plasma malondialdehyde (MDA) concentration decreased in patients with endometriosis after antioxidant vitamin supplementation, and the plasma MDA level was inversely correlated with the time and dose of vitamin E and C supplementation. Furthermore, the inflammatory markers in peritoneal fluid, including RANTES, interleukin-6, and monocyte chemoattractant protein-1, significantly decreased after antioxidant therapy. These findings suggest that antioxidant vitamins may alleviate pain in endometriosis patients by reducing inflammation. CONCLUSIONS: The included studies support the potential role of antioxidant vitamins in the management of endometriosis. Supplementation with antioxidant vitamins effectively reduced the severity of dysmenorrhea, improved dyspareunia and pelvic pain, and enhanced quality of life in these patients. Therefore, antioxidant vitamin therapy could be considered as an alternative treatment method, either alone or in combination with other approaches, for endometriosis-related pain. TRIAL REGISTRATION: PROSPERO registration number: CRD42023415198.

Effect of Systemic Lidocaine on Postoperative Early Recovery Quality in Patients Undergoing Supratentorial Tumor Resection.

Purpose: Lidocaine has been gradually used in general anesthesia. This study was designed to investigate the effect of systemic lidocaine on postoperative quality of recovery (QoR) in patients undergoing supratentorial tumor resection, and to explore its brain-injury alleviation effect in neurosurgical anesthesia. Patients and Methods: Sixty adult patients undergoing elective supratentorial tumor resection. Patients were randomly assigned either to receive lidocaine (Group L: 1.5 mg/kg bolus completed 10 min before anesthesia induction followed by an infusion at 2.0 mg/kg/h) or to receive normal saline (Group C: received volume-matched normal saline at the same infusion rate). Primary outcome measures were Quality of Recovery-40 (QoR-40) scores on postoperative day (POD) 1 and 2. Plasma concentrations of S100B protein (S100B), neuron specific enolase (NSE), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) before anesthesia induction and at the end of surgery were assessed. Visual Analogue Scale (VAS) scores were assessed at 1, 2, 6, 12, 24 and 48 h after surgery. Perioperative parameters and adverse events were also recorded. Results: Patients between two groups had comparable baseline characteristics. Global QoR-40 scores on POD 1 and POD 2 were significantly higher (P <0.001) in group L (165.5±3.8 vs 173.7±4.7) than those in group C (155.6±4.0 vs 163.2±4.5); and scores of physical comfort, emotional state, and pain in group L were superior to those in group C (P <0.05). In group L, patients possessed lower plasma concentration of pro-inflammatory factors (IL-6, TNF-α) and brain injury-related factors (S100B, NSE) (P <0.05), consumed less remifentanil and propofol, and experienced lower pain intensity. Multiple linear regression analysis demonstrated age and pain were correlated with postperative recovery quality. Conclusion: Systemic lidocaine improved early recovery quality after supratentorial tumor resection with general anesthesia, and had certain brain-injury alleviation effects. These benefits may be attributed to the inflammation-alleviating and analgesic properties of lidocaine.

Diagnostic value of acid phosphatases (ACP) in differentiating reactive mesothelial cells from cancer cells in the body fluid effusions.

BACKGROUND: The cytological diagnosis of a malignant epithelial tumor, i.e., a cancer cell in the body fluid effusions is usually made by cytomorphological examination alone; however, diagnostic challenges can occur when the cancer cells are rare or cytological atypia is minimal. Morphological similarity between the cancer and the reactive mesothelial cell is the most common problem in establishing a clear diagnosis. The aim of this study is to investigate whether the cocktail acid phosphatases (ACP) special staining will be a useful tumor marker in differentiation of the reactive mesothelial cells from the cancer cells in the body fluid effusions. METHODS: The cocktail ACP special staining was performed on 212 body fluid effusion samples, which included 128 pleural effusions, 69 ascites, and 15 pericardial effusions. RESULTS: The mesothelial cells were cocktail ACP positive in 84 out of 84 benign effusion cases, and the sensitivity and the specificity were 100% for the benign effusions which including pleural effusions, ascites, and pericardial effusions. On the other hand, 122 out of 128 cancer cases were cocktail ACP negative, indicating that the sensitivity of using the cocktail ACP staining to rule out the malignant effusions was 95.3%. Thus, the cocktail ACP staining is an excellent marker with high sensitivity and specificity to distinguish the carcinoma from the reactive mesothelial cells in the body fluid effusions. CONCLUSIONS: Our finding provided a new tool for cytopathologists in diagnosing the body fluid effusion that could impact clinical decision making.

17beta-estradiol combined with testosterone promotes chicken osteoblast proliferation and differentiation by accelerating the cell cycle and inhibiting apoptosis in vitro.

Medullary bone is a unique tissue in the long bones cavities of lay hens, and plays an important role as a calcium reservoir for egg-shell formation. Medullary bone formation requires the synergistic action of estrogen and androgen on osteoblasts during the early stage of sexual maturity. The objective of the current study was to investigate the effects of 17beta-estradiol, testosterone, and the combination on the proliferation, alkaline phosphatase (ALP) activity, apoptosis, the cell cycle of chicken osteoblasts in vitro. The proliferation of osteoblasts was examined with the MTT assay. Apoptosis and the cell cycle were assessed with flow cytometry. Either 17beta-estradiol (200 pg ml(-1)) or testosterone (100 pg ml(-1)) or the combination (100 pg ml(-1) each) significantly enhanced osteoblast proliferation and ALP activity, accelerated the osteoblast cell cycle, and stimulated osteoblast DNA synthesis in a period of 24 h. 17beta-estradiol, used alone or with testosterone, inhibited chicken osteoblast apoptosis; However, testosterone alone induced cell apoptosis. In conclusion, 17beta-estradiol combined with testosterone promoted osteoblast proliferation and ALP activity, accelerated the osteoblast cell cycle, inhibited osteoblast apoptosis.