Randomized, Single-Blind, Comparative Study of Remimazolam Besylate vs Propofol for Facial Plastic Surgery.

BACKGROUND: Use of local anesthesia and conscious sedation with a combination of a sedative and anesthetic drug during a surgical procedure is an approach designed to avoid intubation, which produces fewer adverse events compared to general anesthesia. In the present study, a comparison was made between the efficacy and safety of remimazolam besylate and propofol for facial plastic surgery. OBJECTIVES: The objective was to evaluate the clinical efficacy, comfort, and incidence of adverse events of remimazolam compared with propofol combined with alfentanil in outpatient facial plastic surgery. METHODS: In this randomized, single-blind, single-center, comparative study, facial plastic surgery patients were randomly divided into remimazolam-alfentanil (n = 50) and propofol-alfentanil (n = 50) groups for sedation and analgesia. The primary endpoint was the incidence of hypoxemia, while secondary endpoints included efficacy and safety evaluations. RESULTS: There were no significant differences regarding the surgical procedure, sedation and induction times, pain and comfort scores, muscle strength recovery, heart rate, respiratory rate, and blood pressure, but the dosage of alfentanil administered to the remimazolam group (387.5 µg) was lower than that for the propofol group (600 µg). The incidence of hypoxemia (P = .046) and towing of the mandibular (P = .028), as well as wake-up (P = .027) and injection pain (P = .008), were significantly higher in the propofol group than the remimazolam group. CONCLUSIONS: Remimazolam and propofol had similar efficacies for sedation and analgesia during facial plastic surgery, but especially the incidence of respiratory depression was significantly lower in patients given remimazolam.

Lysine demethylase 5C inhibits transcription of prefoldin subunit 5 to activate c-Myc signal transduction and colorectal cancer progression.

BACKGROUND: Lysine demethylase 5C (KDM5C) has been implicated in the development of several human cancers. This study aims to investigate the role of KDM5C in the progression of colorectal cancer (CRC) and explore the associated molecular mechanism. METHODS: Bioinformatics tools were employed to predict the target genes of KDM5C in CRC. The expression levels of KDM5C and prefoldin subunit 5 (PFDN5) in CRC cells were determined by RT-qPCR and western blot assays. The interaction between KDM5C, H3K4me3, and PFDN5 was validated by chromatin immunoprecipitation. Expression and prognostic values of KDM5C and PFDN5 in CRC were analyzed in a cohort of 72 patients. The function of KDM5C/PFDN5 in c-Myc signal transduction was analyzed by luciferase assay. Silencing of KDM5C and PFDN5 was induced in CRC cell lines to analyze the cell malignant phenotype in vitro and tumorigenic activity in nude mice. RESULTS: KDM5C exhibited high expression, while PFDN5 displayed low expression in CRC cells and clinical CRC samples. High KDM5C levels correlated with poor survival and unfavorable clinical presentation, whereas elevated PFDN5 correlated with improved patient outcomes. KDM5C mediated demethylation of H3K4me3 on the PFDN5 promoter, suppressing its transcription and thereby enhancing the transcriptional activity of c-Myc. KDM5C knockdown in CRC cells suppressed cell proliferation, migration and invasion, epithelial-mesenchymal transition, and tumorigenic activity while increasing autophagy and apoptosis rates. However, the malignant behavior of cells was restored by the further silencing of PFDN5. CONCLUSION: This study demonstrates that KDM5C inhibits PFDN5 transcription, thereby activating c-Myc signal transduction and promoting CRC progression.

The Number of Intraoperative Intestinal Venous Circulating Tumor Cells Is a Prognostic Factor for Colorectal Cancer Patients.

Purpose: To assess the association between intestinal venous blood (IVB) circulating tumor cells (CTCs) and clinicopathological parameters in stage I-III colorectal cancer (CRC) patients. Methods: Participants were retrospectively retrieved, who were admitted to our hospital or took annual physical exams between December 1, 2015 and December 31, 2018. A negative enrichment-immunofluorescence in situ hybridization (NE-imFISH) technique was used to isolate and identify CTCs. Receiver operating characteristic (ROC) curves and Youden index values were used to determine the critical CTC cutoff value for the diagnosis of CRC. Kaplan-Meier and log-rank methods were used to conduct survival analyses, and multivariate Cox regression analyses were employed for multivariate corrections to comprehensively evaluate the value of CTCs in the diagnosis of CRC. Relationships between IVB CTCs, clinicopathological parameters, and prognosis were then analyzed based upon patient postoperative follow-up data. Results: In total, we retrieved 282 patients including 48 healthy controls, 72 patients with benign colorectal tumors, and 162 CRC patients. CRC patients exhibited significantly higher numbers of CTCs relative to control patients or those with benign disease. CTC numbers in CRC patient peripheral blood (PB) and IVB were closely associated with tumor node metastasis (TNM) staging (P < 0.01), carbohydrate antigen-125 (CA-125) levels (P < 0.001), and KRAS (Kirsten rat sarcoma virus oncogene) mutation status (P < 0.001). The disease-free survival (DFS) of patients in the CTC-negative group was significantly longer than that of patients in the CTC-positive group (24.60 ± 13.31 months vs. 18.70 ± 10.19 months, P < 0.05), with the same being true with respect to their overall survival (OS) (30.60 ± 12.44 months vs. 35.25 ± 11.57 months, P < 0.05). A multivariate analysis revealed that the detection ≥2 CTCs/3.2 ml was independently associated with poorer DFS and OS. CTC counts were independently predictive of CRC patients TNM staging, CA-125, and KRAS mutation status in both univariate and multivariate Cox proportional hazards regression analyses. Conclusion: CTCs are valuable biomarkers that can be monitored to predict CRC patient disease progression.

Mucin 16 Promotes Colorectal Cancer Development and Progression Through Activation of Janus Kinase 2.

BACKGROUND: Mucin 16 (MUC16), a cell surface-associated mucin, has been implicated to be upregulated in a large repertoire of malignances. However, its function in the pathogenesis of colorectal cancer (CRC) is unknown. AIMS: Here, we explored the regulatory role of MUC16 in CRC. METHODS: First, tumor and paracancerous tissues, and serum samples from 162 CRC patients, peripheral blood samples from 48 healthy volunteers and 72 benign colorectal patients were collected. The correlation between the MUC16 expression and the clinical phenotypes of the patients was analyzed. Subsequently, HCT116 and SW480 cells with deletion of MUC16 were established to detect changes in the growth and metastatic capacities of CRC cells. The genes with the highest correlation with MUC16 were predicted by bioinformatics, and their binding relationships were detected by Co-IP and double-labeled immunofluorescence, followed by functional rescue experiments. RESULTS: Overexpression of MUC16 in CRC patients was positively correlated with serum biomarkers and poor prognosis of patients. It was demonstrated by in vitro and in vivo experiments that knocking-down the expression of MUC16 could significantly inhibit the growth and metastasis of CRC cells. MUC16 activated janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) by interacting with JAK2. Further overexpression of JAK2 in cells with poor expression of MUC16 revealed a significant increase in the proliferative and metastatic capacities of CRC cells. CONCLUSIONS: MUC16 contributes to the development and progression of CRC by binding to JAK2, thereby promoting phosphorylation of JAK2 and further activating STAT3 phosphorylation.

Application of comprehensive u nit-based safety program model in the inter-hospital transfer of patients with critical diseases: a retrospective controlled study.

BACKGROUND: To explore the effect of applying a comprehensive unit-based safety program (CUSP) in the intrahospital transfer of patients with critical diseases. METHODS: A total of 426 critically ill patients in the first affiliated Hospital of Anhui Medical University from August 2018 to February 2019 were divided into two groups according to the time of admission. Overall, 202 patients in the control group were treated with the routine transfer method, and 224 patients in the observational group were treated with the transfer method based on the CUSP model. The safety culture assessment data of medical staff, the occurrence rate of adverse events and related causes, the time of transfer, and the satisfaction of patients' relatives to the transfer process were compared before and after implementation of the transfer model between the two groups. RESULTS: Before and after the implementation of the CUSP mode transfer program, there were significant differences in the scores of all dimensions of the safety culture assessment of medical staff (P < 0.05), and the occurrence rate of adverse events and the causes in the observational group were significantly lower than those in the control group (disease-related, staff-related, equipment-related, environment-related) (P < 0.05). The transfer time for Computed Tomography (CT), Magnetic Resonance Imaging (MRI), operating room, and the interventional room was significantly shorter in the observational group than that in the control group (P < 0.05), while the satisfaction of relatives to the transfer process was significantly higher than those in the control group (P < 0.05). CONCLUSION: The implementation of CUSP model for the intrahospital transfer of critically ill patients can significantly shorten the in-hospital transfer time, improve the attitude of medical staff towards safety, reduce the occurrence rate of adverse events, and improve the satisfaction of patients' relatives to the transfer process.

Upregulation lnc-NEAT1 contributes to colorectal cancer progression through sponging miR-486-5p and activating NR4A1/Wnt/ß-catenin pathway.

Colorectal cancer is a major public health problem and fourth guiding cause of cancer-induced mortality worldwide. The five-year survival rate for patients with colorectal cancer remains poor, and almost half of colorectal cancer patients present recurrence and die within five years. The increasing studies showed that long non-coding RNA (lncRNA) was involved in colorectal cancer. Therefore, this study was used to explore molecular mechanisms of nuclear paraspeckle assembly transcript 1 (NEAT1) in colorectal cancer. The real-time quantitative polymerase chain reaction (RT-qPCR) was employed to estimate the expression levels of NEAT1, Nuclear receptor 4 A1 (NR4A1), and miR-486-5p in colorectal cancer tissues and cells. Kaplan-Meier curve was conducted to analyze relationship between survival time of colorectal cancer patients and level of NEAT1. The protein levels of NR4A1, ß-catenin, c-Myc, and cyclinD1 were assessed with western blot assay. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT) and flow cytometry assays were performed to evaluate proliferation and apoptosis of colorectal cancer cells, respectively. The migration and invasion abilities of cells were examined by transwell assay. The relationship between miR-486-5p and NEAT1 or NR4A1 was confirmed by dual-luciferase reporter assay. We found NEAT1 and NR4A1 were highly expressed in colorectal cancer tissues and cell lines compared with controls. Loss-functional experiments revealed that knockdown of NEAT1 or NR4A1 repressed proliferation and motility, while inducing apoptosis of colorectal cancer cells. The gain of NR4A1 could abolish NEAT1 silencing-induced effects in colorectal cancer cells. In addition, NEAT1 contributed to colorectal cancer progression through mediating NR4A1/Wnt/ß-catenin signaling pathway. In conclusion, NEAT1 stimulated colorectal cancer progression via acting as competing endogenous RNA to sponge miR-486-5p and regulate NR4A1/Wnt/ß-catenin signaling pathway.

Comprehensive Analysis of Alternative Splicing Signature in Gastric Cancer Prognosis Based on The Cancer Genome Atlas (TCGA) and SpliceSeq Databases.

BACKGROUND Increasing evidence suggests that the alternative splicing (AS) signature plays a role in the carcinogenesis and prognosis of various cancers. However, the prognostic role of AS in gastric cancer is not clear and needs to be clarified. MATERIAL AND METHODS To identify the differentially expressed AS (DEAS) events, we performed a differential expression analysis between normal and tumor tissue. The DEAS event was further applied to construct a prognostic signature by performing univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) analysis. The Kaplan-Meier curve analysis and receiver operating characteristic curve (ROC) analysis were used to evaluate the prognostic value of the AS signature. In addition, the network of the splicing events with splicing factors was constructed using the Cytoscape software. RESULTS A total of 30 005 alternative splicing (AS) events with 372 patients were retrieved from the SpliceSeq database and TCGA database. By performing differential expression analysis, a total of 419 alternative splicing events were screened out, including 56 upregulated and 363 downregulated. We further constructed an AS-related prognostic signature by conducting a series bioinformatics analyses. Moreover, we identified that the AS signature could serve as an independent predictor for the prognosis of GC. We also found that AS signature had a more robust and precise efficacy for prognostic prediction in GC patients. Interestingly, the areas under 3- and 5-year survival curves are similar, both of which are greater than 1-year survival curve, suggesting that the long-term predictive accuracy of our prognostic model built upon AS signature is superior. CONCLUSIONS We performed a comprehensive analysis of overall prognostic-associated AS events concerning GC and constructed a prognostic model to predict the long-term prognostic survival outcomes in GC patients. We also developed a network of splicing events with splicing factors to reveal new potential molecular diagnostic biomarkers and therapeutic targets for GC patients.