Exploration of treatment strategies and susceptibility gene of postoperative nausea and vomiting in breast cancer patients: a randomised controlled trial.

BACKGROUND: A history of severe nausea and vomiting during pregnancy (SNVP) is a risk factor for postoperative nausea and vomiting (PONV). This study aimed to explore potentially effective treatment strategies and potential genetic factors underlying SNVP risk-related PONV. METHODS: A total of 140 female patients undergoing breast cancer surgery were assigned to either the study group (70 with SNVP) or the control group (70 with mild to moderate nausea and vomiting during pregnancy (MNVP)). Patients in each group were randomly assigned to two different treatment subgroups and received either ondansetron plus dexamethasone (OD) or OD + TEAS (ODT) (transcutaneous electrical acupoint stimulation, TEAS). Blood samples were collected from patients before induction (D0) and 24 h (D1) after surgery for growth differentiation factor 15 (GDF-15) evaluation. The primary outcome was the incidence of PONV within 36 h. The secondary outcome was the serum GDF-15 level. RESULTS: The incidence of PONV in the SNVP group was significantly higher than that in the MNVP group within 24 h (P < 0.005). In the SNVP group, ODT-treated patients had less PONV than those in the OD-treated group during the 6-12 h (P = 0.033) and 12-24 h (P = 0.008) intervals, while within 6 h, there were fewer vomiting cases in the ODT-treated group (SNVP-ODT vs. SNVP-OD, 7/33 vs. 19/35, P = 0.005). The preoperative GDF-15 serum levels in patients with SNVP were significantly higher (P = 0.004). Moreover, higher preoperative GDF-15 serum levels correlated with a higher incidence of PONV (P = 0.043). CONCLUSIONS: TEAS showed significant effect on PONV treatment in patients with SNVP. A higher serum GDF-15 level was associated with a history of SNVP, as well as a higher risk of PONV.

Transcriptomic analysis and experiments revealed that remimazolam promotes proliferation and G1/S transition in HCT8 cells.

Background: Remimazolam is a new ultrashort-acting benzodiazepine for sedation and anesthesia. The effects of remimazolam and the mechanism by which it functions in cancer cells have not been determined. This research aimed to explore the mechanism of remimazolam action in colon cancer treatment, using bioinformatics analysis and in vitro experiments. Methods: Cell cycle progression, colony formation, self-renewal capacity, and apoptosis detection were performed in HCT8 cells treated with or without remimazolam. Transcriptome sequencing, Gene Ontology, Kyoto Encyclopedia of Genes and Genome, Protein-Protein Interaction, Gene Set Enrichment Analysis, Western blotting, and qPCR were performed to investigate the mechanism of action of remimazolam in HCT8 colon cancer cells. Results: Remimazolam promoted proliferation and cell-cycle progression of HCT8 cells. After remimazolam treatment, a total of 1,096 differentially expressed genes (DEGs) were identified: 673 genes were downregulated, and 423 genes were upregulated. The DEGs were enriched mainly in "DNA replication", "cell cycle", and "G1/S transition" related pathways. There were 15 DEGs verified by qPCR, and representative biomarkers were detected by Western Bloting. The remimazolam-mediated promotion of cell proliferation and cell cycle was reversed by G1T28, a CDK4/6 inhibitor. Conclusion: Remimazolam promoted cell-cycle progression and proliferation in HCT8 colon cancer cells, indicating that the long-term use of remimazolam has potential adverse effects in the anesthesia of patients with colon cancer.

Advances of Smart Stimulus-Responsive Microneedles in Cancer Treatment.

Microneedles (MNs) have emerged as a highly promising technology for delivering drugs via the skin. They provide several benefits, including high drug bioavailability, non-invasiveness, painlessness, and high safety. Traditional strategies for intravenous delivery of anti-tumor drugs have risks of systemic toxicity and easy development of drug resistance, while MN technology facilitates precise delivery and on-demand release of drugs in local tissues. In addition, by further combining with stimulus-responsive materials, the construction of smart stimulus-responsive MNs can be achieved, which can respond to specific physical/chemical stimuli from the internal or external environment, thereby further improving the accuracy of tumor treatment and reducing toxicity to surrounding tissues/cells. This review systematically summarizes the classification, materials, and reaction mechanisms of stimulus-responsive MNs, outlines the benefits and challenges of various types of MNs, and details their application and latest progress in cancer treatment. Finally, the development prospects of smart MNs in tumor treatment are also discussed, bringing inspiration for future precision treatment of tumors.

Propofol inhibits colon cancer cell stemness and epithelial-mesenchymal transition by regulating SIRT1, Wnt/ß-catenin and PI3K/AKT/mTOR signaling pathways.

BACKGROUND: Propofol is a common sedative-hypnotic drug used for general anesthesia. Recent studies have drawn attention to the antitumor effects of propofol, but the potential mechanism by which propofol suppresses colon cancer stemness and epithelial-mesenchymal transition (EMT) has not been fully elucidated. METHODS: For the in vitro experiments, we used propofol to treat LOVO and SW480 cells and Cell Counting Kit-8 (CCK-8) to detect proliferation. Self-renewal capacity, cell invasion and migration, flow cytometry analysis, qPCR and Western blotting were performed to detect the suppression of propofol to colon cancer cells and the underlying mechanism. Tumorigenicity and immunohistochemistry experiments were performed to confirm the role of propofol in vivo. RESULT: We observed that propofol could suppressed stem cell-like characteristics and EMT-related behaviors, including self-renewal capacity, cell invasion and migration in colon cancer cells, and even suppressed tumorigenicity in vivo. Furthermore, investigations of the underlying mechanism revealed that propofol treatment downregulated SIRT1. SIRT1 overexpression or knockdown affected the stemness and EMT of colon cancer cells. Additionally, propofol reversed stemness and EMT in cells with overexpressing SIRT1 and subsequently inhibited the Wnt/ß-catenin and PI3K/AKT/mTOR signaling pathways. Wnt/ß-catenin pathway inhibitor and PI3K/AKT/mTOR pathway inhibitor blocked the propofol-induced reduction of sphere-formation and cell invasion-migration. CONCLUSION: Propofol inhibits LOVO and SW480 cell stemness and EMT by regulating SIRT1 and the Wnt/ß-catenin and PI3K/AKT/mTOR signaling pathways. Our findings indicate that propofol inhibits SIRT1 in cancer and is advantageous in colon cancer surgical treatment of patients with high SIRT1 expression.

LncRNA Riken Attenuated Sevoflurane-Induced Neuroinflammation by Regulating the MicroRNA-101a/MKP-1/JNK Pathway.

The induction of anesthesia in children makes its safety one of the most important global health problems. Neuroinflammation contributes to anesthesia-induced neurotoxicity in young individuals. However, the mechanisms underlying anesthesia-induced neurotoxicity have not been established. In this study, the level of interleukin (IL)-6 in the hippocampus of mice and N2A cells treated with sevoflurane was increased, and long noncoding RNA (LncRNA) Riken was sufficient to decrease sevoflurane-induced neurotoxicity, and the level of inflammatory cytokine IL-6. The RNA pull-down assay verified that miR-101a was bound to lncRNA Riken in N2A cells. In addition, miR-101a blocked the protective effect of lncRNA Riken on anesthesia-induced neuroinflammation. These data suggest that lncRNA Riken attenuated anesthesia-induced neuroinflammation by interacting with microRNA-101a. Finally, we also demonstrated that MAPK phosphatase 1 (MKP-1) was a downstream target of miR-101a, and lncRNA Riken can regulate the expression of MKP-1; the JNK signal transduction pathway has been implicated in sevoflurane-induced IL-6 secretion. Our findings demonstrated that lncRNA Riken alleviated the sevoflurane-induced neurotoxic effects, and the lncRNA Riken/miR-101a/MKP-1/JNK axis plays an important role in the cognitive disorder.

Incidence features of second primary malignancy among gastric cancer survivors, 1992-2012.

BACKGROUND: With the expanding population of cancer survivors, screening for second primary malignancy (SPM) is one issue concerning survivorship care. This study aimed to evaluate the potential risk of developing SPMs and determine the features of SPMs among patients after the diagnosis of gastric cancer (GC). METHODS: We identified 33,705 GC patients from the Surveillance, Epidemiology, and End Results Program (SEER) database. The standardized incidence ratios (SIRs) were calculated to estimate the risk of SPMs. The SIRs were stratified by age, race, stage, and latency period since GC diagnosis. RESULTS: A total of 2,018 among 33,705 GC patients developed SPMs. Compared with the general population, these GC survivors had higher risks of developing second malignancies of the esophagus, stomach, small intestine, colon, pancreas, and thyroid. Conversely, these GC survivors had lower chances of developing prostate and female breast cancer. CONCLUSIONS: In stratified analyses, we identified the features associated with a higher risk of developing SPMs, including age between 20 and 39 years, latency between 60 and 119 months, localized stage, and American Indian/Alaska Native ethnicity. Hence, GC survivors are at a higher risk of developing SPMs than the general population. Careful attention and continuous surveillance should be used when treating these patients.