Introduction: Cervical cancer is common in women. The present standardized therapies including surgery, chemotherapy, and radiotherapy are still not enough for treatment. Propofol is the most commonly used intravenous anesthetic agent for induction and maintenance of anesthesia and has been shown to exert anti-malignancy effects on cancer cells, inducing oxidative stress and apoptosis. However, the biological effects of propofol have not yet been systematically assessed. In this study, we examined the ferroptosis-related changes caused by propofol and the chemotherapeutic agent paclitaxel besides apoptosis in vitro.Methods: Cervical cancer cell lines (C-33A and HeLa) were treated with propofol alone (1, 2, 5, 10, and 20 μg/ml) or in combination with paclitaxel (0.5, 1, and 5 μg/ml). The viability was assessed using cell counting kit-8 (CCK8), apoptosis was detected by flow cytometry, morphological changes of mitochondria were examined using transmission electron microscope (TEM), cellular reactive oxygen species (ROS), and intracellular ferrous ions were determined by fluorescence microscope or confocal microscopy. The expression and cellular localization of apoptosis and ferroptosis-related molecules were detected by Western blot and multiplex immunohistochemistry (mIHC), respectively. Calcusyn software was used to determine whether propofol has a synergistic effect with paclitaxel.Results: Propofol and paclitaxel inhibited C-33A and HeLa cell viability. There were also synergistic effects when propofol and paclitaxel were used in combination at certain concentrations. In addition, propofol promoted paclitaxel-induced cervical cancer cell death via apoptosis. ROS level and Fe²⁺ concentrations were also influenced by different drug treatments. Furthermore, propofol, propofol injectable emulsion, and paclitaxel induced ferroptosis-related morphological changes of mitochondria in C-33A and HeLa cells. Ferroptosis-related signaling pathways including SLC7A11/GPX4, ubiquinol/CoQ10/FSP1, and YAP/ACSL4/TFRC were found to be changed under drug treatments.Conclusion: Propofol showed synergistic anticancer effects with paclitaxel in cervical cancer cells. Propofol and paclitaxel may induce ferroptosis of cervical cancer cells besides apoptosis.

Background: Triple-negative breast cancer (TNBC) is relatively common in women and is associated with a poor prognosis after surgery and adjuvant chemotherapy. Currently, the mechanism underlying the relationship between propofol and breast cancer is controversial and limited to cell apoptosis. Moreover, there are only a few studies on the effect of propofol on the chemotherapeutic sensitivity of TNBC cells. Therefore, this study explored whether propofol and its commonly used clinical formulations affect the proliferation and chemotherapeutic effects on TNBC cells by regulating cell ferroptosis.Methods: We selected MDA-MB-231 cells, and the effects of propofol, propofol injectable emulsion (PIE), or fospropofol disodium, alone or combined with doxorubicin or paclitaxel on cell viability, apoptosis, intracellular reactive oxygen species (ROS) accumulation, ferroptosis-related morphological changes, intracellular Fe²⁺ levels, and the expression and localization of ferroptosis-related proteins were investigated.Results: We found that propofol significantly inhibited MDA-MB-231 cell proliferation, and all three propofol formulations augmented the anti-tumor effects of doxorubicin and paclitaxel. The results from the ROS assay, transmission electron microscopy, intracellular Fe²⁺ assay, western blotting, and multiplex immunohistochemistry revealed that propofol not only induced apoptosis but also triggered ferroptosis-related changes, including morphological changes of mitochondria, increased intracellular ROS levels, and intracellular iron accumulation in MDA-MB-231 cells. The ferroptosis-related p53-SLC7A11-GPX4 pathway was also altered under different treatment propofol, doxorubicin, or paclitaxel regimens.Conclusion: Propofol showed anti-proliferation effects on TNBC cells and could be a potential adjuvant to enhance the chemotherapeutic sensitivity of TNBC cells partly by promoting cell ferroptosis.

Purpose: This study aimed to develop prediction models for chronic postsurgical pain (CPSP) after breast cancer surgery using machine learning approaches and evaluate their performance.Methods: The study was a secondary analysis based on a high-quality dataset from a randomized controlled trial (NCT00418457), including patients with primary breast cancer undergoing mastectomy. The primary outcome was CPSP at 12 months after surgery, defined as modified Brief Pain Inventory > 0. The dataset was randomly split into a training dataset (90%) and a testing dataset (10%). Variables were selected using recursive feature elimination combined with clinical experience, and potential predictors were then incorporated into three machine learning models, including random forest, gradient boosting decision tree and extreme gradient boosting models for outcome prediction, as well as logistic regression. The performances of these four models were tested and compared.Results: 1152 patients were finally included, of which 22.1% developed CPSP at 12 months after breast cancer surgery. The 6 leading predictors were higher numerical rating scale within 2 days after surgery, post-menopausal status, urban medical insurance, history of at least one operation, under fentanyl with sevoflurane general anesthesia, and received axillary lymph node dissection. Compared with the multivariable logistic regression model, machine learning models showed better specificity, positive likelihood ratio and positive predictive value, helping to identify high-risk patients more accurately and create opportunities for early clinical intervention.Conclusions: Our study developed prediction models for CPSP after breast cancer surgery based on machine learning approaches, which may help to identify high-risk patients and improve patients’ management after breast cancer.

Background: Whether regional anesthesia may help to prevent disease recurrence in cancer patients is still controversial. The stage of cancer at the time of diagnosis is a key factor that defines prognosis and is one of the most important sources of heterogeneity for the treatment effect. We sought to update existing systematic reviews and clarify the effect of regional anesthesia on cancer recurrence in late-stage cancer patients. Methods: Medline, Embase, and Cochrane Library were searched from inception to September 2020 to identify randomized controlled trials (RCTs) and cohort studies that assessed the effect of regional anesthesia on cancer recurrence and overall survival (OS) compared with general anesthesia. Late-stage cancer patients were primarily assessed according to the American Joint Committee on Cancer Cancer Staging Manual (eighth edition), and the combined hazard ratio (HR) from random-effects models was used to evaluate the effect of regional anesthesia. Results: A total of three RCTs and 34 cohort studies (including 64,691 patients) were identified through the literature search for inclusion in the analysis. The risk of bias was low in the RCTs and was moderate in the observational studies. The pooled HR for recurrence-free survival (RFS) or OS did not favor regional anesthesia when data from RCTs in patients with late-stage cancer were combined (RFS, HR = 1.12, 95% confidence interval [CI]: 0.58–2.18, P = 0.729, I ² = 76%; OS, HR = 0.86, 95% CI: 0.63–1.18, P = 0.345, I ² = 48%). Findings from observational studies showed that regional anesthesia may help to prevent disease recurrence (HR = 0.87, 95% CI: 0.78–0.96, P = 0.008, I ² = 71%) and improve OS (HR = 0.88, 95% CI: 0.79–0.98, P = 0.022, I ² = 79%). Conclusions: RCTs reveal that OS and RFS were similar between regional and general anesthesia in late-stage cancers. The selection of anesthetic methods should still be based on clinical evaluation, and changes to current practice need more support from large, well-powered, and well-designed studies.

Background: Organ/space surgical site infection (organ/space SSI) is a serious postoperative complication, closely related to a poor prognosis. Few studies have attempted to stratify the risk of organ/space SSI for patients with advanced digestive system cancer. This study aimed to identify a simple risk stratification for these patients based on perioperative factors.Methods: The study was based on two randomized controlled trials (RCT) (NCT02715076, ChiCTR-IPR-17011099), including 839 patients undergoing elective radical resection of advanced digestive system cancer. The primary outcome was organ/space SSI within 30 days after surgery. Multivariable logistic regression model was used to identify risk factors. The risk of organ/space SSI stratified over those risk factors was compared using chi-square tests and the relative risk (RR) was estimated.Results: Among the 839 patients, 51 developed organ/space SSI (6.1%) within 30 days after surgery. According to the multivariable logistic regression model, 3 procedure types, including gastrectomy (OR=8.22, 95% CI: 2.71-24.87, P<0.001), colorectal resection (OR=8.65, 95% CI: 3.13-23.85, P<0.001) and pancreatoduodenectomy (OR=7.72, 95% CI: 2.95-20.21, P 4 h (OR=2.38, 95% CI: 1.08-5.27, P=0.032) and prolonged ICU stay (OR=4.10, 95% CI: 1.67-10.10, P=0.002), were risk factors for postoperative organ/space SSI. The number of risk factors was significantly associated with an increased risk of organ/space SSI (P<0.001), which was 2.8% in patients with 0-1 risk factor (RR=0.20, 95% CI: 0.11-0.35), 13.0% in patients with 2 risk factors (RR=3.64, 95% CI: 2.14-6.20) and 35.7% in patients with 3 risk factors (RR=6.41, 95% CI: 3.01-13.65).Conclusion: This study is a preliminary exploratory and provides a simple risk stratification to identify the risk of postoperative organ/space SSI for patients with advanced digestive system cancer. Further research is needed to validate and generalize the results in a wider population.Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02715076; Chinese Clinical Trial Registry [https://www.chictr.org.cn/enindex.aspx], identifier ChiCTR-IPR-17011099.

Tumor resection is the first-line therapy for acromegaly patients. In some cases, unsatisfactory intraoperative neuromuscular blockades (NMBs) lead to failed operations. The purpose of this study was to investigate and quantify the NMB status of acromegaly patients and explore the relationship between NMB status and hormone levels and body composition. Twenty patients with untreated acromegaly and seventeen patients with nonfunctioning pituitary adenomas as controls were enrolled in this study. NMB was assessed using the train-of-four (TOF) technique with TOF-Watch® SX. The onset time of NMB, deep neuromuscular blockade duration (DNMBD), and clinical neuromuscular blockade duration (CNMBD) were monitored. We found a significantly longer onset time (110.25 ± 54.90 vs. 75.00 ± 27.56, s, ), shorter DNMBD (21.99 ± 5.67 vs. 34.96 ± 11.04, min, ), and shorter CNMBD (33.26 ± 8.09 vs. 46.21 ± 10.89, min, ) in acromegaly patients compared with the controls. DNMBD and CNMBD decreased in patients with decreasing body fat percentage and increasing growth hormone (GH) level, insulin-like growth factor 1 (IGF-1) level, and GH and IGF-1 burden. The onset time increased with increasing IGF-1 level and GH and IGF-1 burden. Taken together, a unique NMB status was identified in acromegaly patients with the following characteristics: prolonged onset time and shortened DNMBD and CNMBD. Changes in the levels and burdens of GH and IGF-1 and body composition were linearly correlated with intraoperative NMB in acromegaly patients.