Association between reversal agents (sugammadex vs. neostigmine) for neuromuscular block and postoperative pulmonary complications: A retrospective analysis.

AIMS: Residual neuromuscular blockade has been linked to pulmonary complications in the postoperative period. This study aimed to determine whether sugammadex was associated with a lower risk of postoperative pulmonary complications (PPCs) compared with neostigmine. METHODS: This retrospective cohort study was conducted in a tertiary academic medical center. Patients ≥18 year of age undergoing noncardiac surgical procedures with general anesthesia and mechanical ventilation were enrolled between January 2019 and September 2021. We identified all patients receiving rocuronium and reversal with neostigmine or sugammadex via electronic medical record review. The primary endpoint was a composite of PPCs (including pneumonia, atelectasis, respiratory failure, pulmonary embolism, pleural effusion, or pneumothorax). The incidence of PPCs was compared using propensity score analysis. RESULTS: A total of 1786 patients were included in this study. Among these patients, 976 (54.6%) received neostigmine, and 810 (45.4%) received sugammadex. In the whole sample, PPCs occurred in 81 (4.54%) subjects (7.04% sugammadex vs. 2.46% neostigmine). Baseline covariates were well balanced between groups after overlap weighting. Patients in the sugammadex group had similar risk (overlap weighting OR: 0.75; 95% CI: 0.40 to 1.41) compared to neostigmine. The sensitivity analysis showed consistent results. In subgroup analysis, the interaction P-value for the reversal agents stratified by surgery duration was 0.011. CONCLUSION: There was no significant difference in the rate of PPCs when the neuromuscular blockade was reversed with sugammadex compared to neostigmine. Patients undergoing prolonged surgery may benefit from sugammadex, which needs to be further investigated.

Sirt7/HIC1 complex participates in hyperglycaemia-mediated EndMT via modulation of SDC1 expression in diabetic kidney disease and metabolic memory.

Diabetic kidney disease (DKD), a primary microvascular complication arising from diabetes, may result in end-stage renal disease. Epigenetic regulation of endothelial mesenchymal transition (EndMT) has been recently reported to exert function in metabolic memory and DKD. Here, we investigated the mechanism which Sirt7 modulated EndMT in human glomerular endothelial cells (HGECs) in the occurrence of metabolic memory in DKD. Lower levels of SDC1 and Sirt7 were noted in the glomeruli of both DKD patients and diabetes-induced renal injury rats, as well as in human glomerular endothelial cells (HGECs) with high blood sugar. Endothelial-to-mesenchymal transition (EndMT) was sustained despite the normalization of glycaemic control. We also found that Sirt7 overexpression associated with glucose normalization promoted the SDC1 expression and reversed EndMT in HGECs. Furthermore, the sh-Sirt7-mediated EndMT could be reversed by SDC1 overexpression. The ChIP assay revealed enrichment of Sirt7 and H3K18ac in the SDC1 promoter region. Furthermore, hypermethylated in cancer 1 (HIC1) was found to be associated with Sirt7. Overexpression of HIC1 with normoglycaemia reversed high glucose-mediated EndMT in HGECs. The knockdown of HIC1-mediated EndMT was reversed by SDC1 upregulation. In addition, the enrichment of HIC1 and Sirt7 was observed in the same promoter region of SDC1. The overexpressed Sirt7 reversed EndMT and improved renal function in insulin-treated diabetic models. This study demonstrated that the hyperglycaemia-mediated interaction between Sirt7 and HIC1 exerts a role in the metabolic memory in DKD by inactivating SDC1 transcription and mediating EndMT despite glucose normalization in HGECs.

Efficient organized colorectal cancer screening in Shenzhen: a microsimulation modelling study.

BACKGROUND: Colorectal cancer (CRC) is a global health issue with noticeably high incidence and mortality. Microsimulation models offer a time-efficient method to dynamically analyze multiple screening strategies. The study aimed to identify the efficient organized CRC screening strategies for Shenzhen City. METHODS: A microsimulation model named CMOST was employed to simulate CRC screening among 1 million people without migration in Shenzhen, with two CRC developing pathways and real-world participation rates. Initial screening included the National Colorectal Polyp Care score (NCPCS), fecal immunochemical test (FIT), and risk-stratification model (RS model), followed by diagnostic colonoscopy for positive results. Several start-ages (40, 45, 50 years), stop-ages (70, 75, 80 years), and screening intervals (annual, biennial, triennial) were assessed for each strategy. The efficiency of CRC screening was assessed by number of colonoscopies versus life-years gained (LYG). RESULTS: The screening strategies reduced CRC lifetime incidence by 14-27 cases (30.9-59.0%) and mortality by 7-12 deaths (41.5-71.3%), yielded 83-155 LYG, while requiring 920 to 5901 colonoscopies per 1000 individuals. Out of 81 screening, 23 strategies were estimated efficient. Most of the efficient screening strategies started at age 40 (17 out of 23 strategies) and stopped at age 70 (13 out of 23 strategies). Predominant screening intervals identified were annual for NCPCS, biennial for FIT, and triennial for RS models. The incremental colonoscopies to LYG ratios of efficient screening increased with shorter intervals within the same test category. Compared with no screening, when screening at the same start-to-stop age and interval, the additional colonoscopies per LYG increased progressively for FIT, NCPCS and RS model. CONCLUSION: This study identifies efficient CRC screening strategies for the average-risk population in Shenzhen. Most efficient screening strategies indeed start at age 40, but the optimal starting age depends on the chosen willingness-to-pay threshold. Within insufficient colonoscopy resources, efficient FIT and NCPCS screening strategies might be CRC initial screening strategies. We acknowledged the age-dependency bias of the results with NCPCS and RS.

Nasal splinting and mouth breathing training reduce emergence delirium after endoscopic sinus surgery: a randomized controlled trial.

BACKGROUND: Emergence delirium (ED) is generally occurred after anesthesia associated with increased risks of long-term adverse outcomes. Therefore, this study aimed to evaluate the efficacy of preconditioning with nasal splint and mouth-breathing training on prevention of ED after general anesthesia. METHODS: This randomized controlled trial enrolled 200 adult patients undergoing ESS. Patients were randomized to receive either nasal splinting and mouth breathing training (n = 100) or standard care (n = 100) before surgery. The primary outcome was the occurrence of ED within 30 min of extubation, assessed using the Riker Sedation-Agitation Scale. Logistic regression identified risk factors for ED. RESULTS: Totally 200 patients were randomized and 182 aged from 18 to 82 years with 59.9% of males were included in the final analysis (90 in C-group and 92 in P-group). ED occurred in 16.3% of the intervention group vs. 35.6% of controls (P = 0.004). Male sex, smoking and function endoscopic sinus surgery (FESS) were independent risk factors for ED. CONCLUSIONS: Preoperative nasal splinting and mouth breathing training significantly reduced the incidence of emergence delirium in patients undergoing endoscopic sinus surgery. TRIAL REGISTRATION: ChiCTR1900024925 ( https://www.chictr.org.cn/index.aspx ) registered on 3/8/2019.

Molecular Mechanism of the Saposhnikovia divaricata-Angelica dahurica Herb Pair in Migraine Therapy Based on Network Pharmacology and Molecular Docking.

Objective: This work studied the molecular mechanism of the Saposhnikovia divaricata-Angelica dahurica herb pair (SAHP) in migraine treatment. Methods: The active ingredients of drugs were screened, and potential targets were predicted by the Traditional Chinese Medicine Systems Pharmacology (TCMSP), TCMID, ETCM, and other databases. Migraine-related targets were obtained by harnessing the GeneCards, DrugBank, OMIM, TTD, and other databases. The protein-protein interaction (PPI) network was constructed with STRING software by performing a Venn analysis with bioinformatics. Gene Ontology (GO) functional enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed with the Metascape platform. The component-target-pathway (C-T-P) network was constructed with Cytoscape 3.7.2 software, and molecular docking was assessed with AutoDockVina software. Results: A total of 183 relevant targets and 39 active ingredients in migraine therapy were obtained from SAHP. The active ingredients and targets were screened according to topological parameters: wogonin, anomalin, imperatorin, prangenin, 2-linoleoylglycerol, and methylenetanshinquinone were identified as key active ingredients. PTGS2, PIK3CA, PIK3CB, PIK3CD, F2, and AR were identified as key targets. The molecular docking results demonstrated high binding activity between the key active ingredients and key targets. A total of 20 important signaling pathways, including neural signaling pathways, calcium signaling pathways, pathways in cancer, cAMP signaling pathways, and PI3K-Akt signaling pathways, were obtained through enrichment analysis. Conclusion: Migraine with SAHP is mainly treated through anti-inflammatory and analgesic effects. The herb pair can be used for migraine using "multicomponent, multitarget, and multipathway" approaches.

Current treatment of chronic hepatitis B: Clinical aspects and future directions.

Hepatitis B virus (HBV) infection is a public health threat worldwide, and there is no direct treatment yet available. In the event of infection, patients may present liver cirrhosis and cancer, which threaten the patients' health globally, especially in the Asia-Pacific region and China. In 2019, Chinese hepatopathologists updated the 2015 Guidelines for the Prevention and Treatment of Chronic Hepatitis B as the clinical reference. The other versions formulated by the American Association for the Study of Liver Diseases (2018 AASLD guidelines) (AASLD, 2018), European Association for the Study of the Liver (2017 EASL guidelines) (EASL, 2017), and Asian-Pacific Association for the Study of the Liver (2015 APASL guidelines) (APASL, 2015) also provide clinical guidance. However, there are still some issues that need to be addressed. In the present study, the following aspects will be introduced successively: (1) Who should be treated in the general population according to the guidelines; (2) Treatment of specific populations infected with HBV; (3) Controversial issues in clinical practice; (4) Perspective.

SETD8 cooperates with MZF1 to participate in hyperglycemia-induced endothelial inflammation via elevation of WNT5A levels in diabetic nephropathy.

OBJECTIVE: Diabetic nephropathy (DN) is regarded as the main vascular complication of diabetes mellitus, directly affecting the outcome of diabetic patients. Inflammatory factors were reported to participate in the progress of DN. Wingless-type family member 5 (WNT5A), myeloid zinc finger 1 (MZF1), and lysine methyltransferase 8 (SETD8) have also been reported to elevate inflammatory factor levels and activate the nuclear factor kappa B (NF-κB) pathway to induce endothelial dysfunction. In the current study, it was assumed that MZF1 associates with SETD8 to regulate WNT5A transcription, thus resulting in hyperglycemia-induced glomerular endothelial inflammation in DN. METHODS: The present study recruited 25 diagnosed DN patients (type 2 diabetes) and 25 control participants (nondiabetic renal cancer patients with normal renal function, stage I-II) consecutively. Moreover, a DN rat and cellular model was constructed in the present study. Immunohistochemistry, Western blot, and quantitative polymerase chain reaction (qPCR) were implemented to determine protein and messenger RNA (mRNA) levels. Coimmunoprecipitation (CoIP) and immunofluorescence were implemented in human glomerular endothelial cells (HGECs). Chromatin immunoprecipitation assays and dual luciferase assays were implemented to determine transcriptional activity. RESULTS: The results of this study indicated that levels of WNT5A expression, p65 phosphorylation (p-p65), and inflammatory factors were all elevated in DN patients and rats. In vitro, levels of p-p65 and inflammatory factors increased along with the increase of WNT5A expression in hyperglycemic HGECs. Moreover, high glucose increased MZF1 expression and decreased SETD8 expression. MZF1 and SETD8 inhibit each other under the stimulus of high glucose, but cooperate to regulate WNT5A expression, thus influencing p-p65 and endothelial inflammatory factors levels. Overexpression of MZF1 and silencing of SETD8 induced endothelial p-p65 and inflammatory factors levels, which can be reversed by si-WNT5A. Mechanistic research indicated that MZF1, SETD8, and its downstream target histone H4 lysine 20 methylation (H4K20me1) all occupied the WNT5A promoter region. sh-SETD8 expanded the enrichment of MZF1 on WNT5A promoter. Our in vivo study proved that SETD8 overexpression inhibited levels of WNT5A, p-p65 expression, and inflammatory factors in DN rats. CONCLUSIONS: MZF1 links with SETD8 to regulate WNT5A expression in HGECs, thus elevating levels of hyperglycemia-mediated inflammatory factors in glomerular endothelium of DN patients and rats. Trial registration ChiCTR, ChiCTR2000029425. 2020/1/31, http://www.chictr.org.cn/showproj.aspx?proj=48548.

KMT5A downregulation participated in High Glucose-mediated EndMT via Upregulation of ENO1 Expression in Diabetic Nephropathy.

Diabetic nephropathy (DN) has become the common and principal microvascular complication of diabetes that could lead to end-stage renal disease. It was reported endothelial-to-mesenchymal transition (EndMT) in glomeruli plays an important role in DN. Enolase1 (ENO1) and Lysine Methyltransferase 5A (KMT5A) were found to modulate epithelial-to-mesenchymal transition in some situations. In the present study, we speculated KMT5A regulates ENO1 transcript, thus participating in hyperglycemia-induced EndMT in glomeruli of DN. Our study represented vimentin, αSMA and ENO1 expression elevated, and CD31 expression decreased in glomeruli of DN participants and rats. In vitro, high glucose induced EndMT by increase of ENO1 levels. Moreover, high glucose downregulated KMT5A levels and increased regulatory factor X1 (RFX1) levels. KMT5A upregulation or si-RFX1 decreased high glucose-induced ENO1 expression and EndMT. RFX1 overexpression- or sh-KMT5A-induced EndMT was attenuated by si-ENO1. Further, the association between KMT5A and RFX1 was verified. Furthermore, histone H4 lysine20 methylation (the direct target of KMT5A) and RFX1 positioned on ENO1 promoter region. sh-KMT5A enhanced positive action of RFX1 on ENO1 promoter activity. KMT5A reduction and RFX1 upregulation were verified in glomeruli of DN patients and rats. KMT5A associated with RFX1 to modulate ENO1, thus involved in hyperglycemia-mediated EndMT in glomeruli of DN.

ets1 associates with KMT5A to participate in high glucose-mediated EndMT via upregulation of PFN2 expression in diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is currently the leading cause of end-stage renal disease globally. The endothelial-to-mesenchymal transition (EndMT) of glomerular endothelial cells has been reported to play a crucial role in DN. As a specific form of epithelial-to-mesenchymal transition, EndMT and epithelial-to-mesenchymal transition may exhibit mutual modulators. Profilin 2 (PFN2) has been reported to participate in epithelial-to-mesenchymal transition. Moreover, ETS proto-oncogene 1 (ets1) and lysine methyltransferase 5A (KMT5A) have been reported to contribute to high glucose-mediated endothelial injury and epithelial-to-mesenchymal transition. In this study, we hypothesize ets1 associates with KMT5A to modulate PFN2 transcription, thus participating in high glucose-mediated EndMT in glomerular endothelial cells. METHODS: Immunohistochemistry (IHC) was performed to detect protein levels in the kidney tissues and/or aorta tissues of human subjects and rats. Western blot, qPCR and immunofluorescence were performed using human umbilical vein endothelial cells (HUVECs). Chromatin immunoprecipitation (ChIP) assays and dual luciferase assays were performed to assess transcriptional activity. The difference between the groups was compared by two-tailed unpaired t-tests or one-way ANOVAs. RESULTS: Our data indicated that vimentin, αSMA, S100A4 and PFN2 levels were increased, and CD31 levels were reduced in glomerular endothelial cells of DN patients and rats. Our cell experiments showed that high glucose induced EndMT by augmenting PFN2 expression in HUVECs. Moreover, high glucose increased ets1 expression. si-ets1 suppressed high glucose-induced PFN2 levels and EndMT. ets1 overexpression-mediated EndMT was reversed by si-PFN2. Furthermore, ets1 was determined to associate with KMT5A. High glucose attenuated KMT5A levels and histone H4 lysine 20 methylation (H4K20me1), one of the downstream targets of KMT5A. KMT5A upregulation suppressed high glucose-induced PFN2 levels and EndMT. sh-KMT5A-mediated EndMT was counteracted by si-PFN2. Furthermore, H4K20me1 and ets1 occupied the PFN2 promoter region. sh-KMT5A cooperated with ets1 overexpression to activate PFN2 promoter activity. Our in vivo study demonstrated that KMT5A was reduced, while ets1 was augmented, in glomerular endothelial cells of DN patients and rats. CONCLUSIONS: The present study indicated that ets1 cooperated with KMT5A to transcribe PFN2, thus contributing to hyperglycemia-induced EndMT in the glomerular endothelial cells of DN patients and rats. Trial registration ChiCTR, ChiCTR2000029425. 2020/1/31, http://www.chictr.org.cn/showproj.aspx?proj=48548.

SET8 suppression mediates high glucose-induced vascular endothelial inflammation via the upregulation of PTEN.

Hyperglycemia-mediated endothelial inflammation participates in the pathogenesis of cardiovascular complications in subjects with diabetes. Previous studies reported that phosphatase and tensin homolog deleted on chromosome ten (PTEN) and SET8 participate in high glucose-mediated endothelial inflammation. In this study, we hypothesize that SET8 regulates PTEN expression, thus contributing to high glucose-mediated vascular endothelial inflammation. Our data indicated that plasma soluble intercellular adhesion molecule-1 (sICAM-1) and endothelial selectin (e-selectin) were increased in patients with diabetes and diabetic rats. PTEN expression was augmented in the peripheral blood mononuclear cells of patients with diabetes and in the aortic tissues of diabetic rats. Our in vitro study indicated that high glucose increased monocyte/endothelial adhesion, endothelial adhesion molecule expression and p65 phosphorylation in human umbilical vein endothelial cells (HUVECs). Moreover, high glucose led to endothelial inflammation via upregulation of PTEN. Furthermore, high glucose inhibited SET8 expression and histone H4 lysine 20 methylation (H4K20me1), a downstream target of SET8. SET8 overexpression reversed the effects of high-glucose treatment. shSET8-mediated endothelial inflammation was counteracted by siPTEN. Furthermore, SET8 was found to interact with FOXO1. siFOXO1 attenuated high glucose-mediated endothelial inflammation. FOXO1 overexpression-mediated endothelial inflammation was counteracted by siPTEN. H4K20me1 and FOXO1 were enriched in the PTEN promoter region. shSET8 increased PTEN promoter activity and augmented the positive effect of FOXO1 overexpression on PTEN promoter activity. Our in vivo study indicated that SET8 was downregulated and FOXO1 was upregulated in the peripheral blood mononuclear cells of patients with diabetes and the aortic tissues of diabetic rats. In conclusion, SET8 interacted with FOXO1 to modulate PTEN expression in vascular endothelial cells, thus contributing to hyperglycemia-mediated endothelial inflammation.

Efficacy analysis of intraoperative radiotherapy in patients with early-stage breast cancer.

BACKGROUND: To analyze the clinical efficacy of intraoperative radiotherapy (IORT) after breast-conserving surgery (BCS) in patients with early-stage breast cancer (BC), and to investigate the relationship between its influencing factors and clinical efficacy and prognosis. METHODS: A total of 73 patients with early-stage BC who underwent IORT after BCS in our hospital were selected in this research. RESULTS: Kaplan-Meier survival analysis was used to analyze the related factors of BCS and IORT of disease-free survival (DFS) and overall survival (OS). It was found that only age (χ2 = 14.035, P = 0.003) was statistically positively correlated with the patient's DFS, and local recurrence and metastasis rate and mortality were higher in patients over 70 years old. Log rank test was used to analyze multiple factors. Only the diameter of the applicator (χ2 = 70.378, P < 0.05) was statistically significant with wound complications, and the larger the diameter, the higher incidence of wound complications. The remaining risk factors did not increase the incidence of wound complications. COX multivariate analysis showed that age was an independent risk factor for DFS rate and the risk factor had no significant effect on the OS rate of patients undergoing IORT after BCS. CONCLUSIONS: IORT may be a safe form of treatment for the selected patients with early-stage BC, and can achieve satisfactory esthetic effect. Larger applicator diameters may increase the incidence of wound complications. Age is an independent risk factor for DFS in early-stage BC patients undergoing IORT after BCS.

Association between intraoperative intravenous lidocaine infusion and survival in patients undergoing pancreatectomy for pancreatic cancer: a retrospective study.

BACKGROUND: Intravenous lidocaine has been shown to reduce opioid consumption and is associated with favourable outcomes after surgery. In this study, we explored whether intraoperative lidocaine reduces intraoperative opioid use and length of stay (LOS) and improves long-term survival after pancreatic cancer surgery. METHODS: This retrospective study included 2239 patients who underwent pancreatectomy from January 2014 to December 2017. The patients were divided into non-lidocaine and lidocaine (bolus injection of 1.5 mg kg-1 at the induction of anaesthesia followed by a continuous infusion of 2 mg kg-1 h-1 intraoperatively) groups. The overall use of postoperative rescue analgesia and LOS were recorded. Propensity score matching was used to minimise bias, and disease-free survival and overall survival were compared between the two groups. RESULTS: After propensity score matching, patient characteristics were not significantly different between groups. Intraoperative sufentanil consumption and use of postoperative rescue analgesia in the lidocaine group were significantly lower than those in the non-lidocaine group. The LOS was similar between groups. There was no significant difference in disease-free survival between groups (hazard ratio [HR]=0.913; 95% confidence interval [CI], 0.821-1.612; P=0.316). The overall survival rates at 1 and 3 yr were significantly higher in the lidocaine group than in the non-lidocaine group (68.0% vs 62.6%, P<0.001; 34.1% vs 27.2%, P=0.011). The multivariable analysis indicated that intraoperative lidocaine infusion was associated with a prolonged overall survival (HR=0.616; 95% CI, 0.290-0.783; P=0.013). CONCLUSION: Intraoperative intravenous lidocaine infusion was associated with improved overall survival in patients undergoing pancreatectomy.

High glucose mediates NLRP3 inflammasome activation via upregulation of ELF3 expression.

Microtubule affinity regulating kinase 4 (MARK4) plays a crucial role in the regulation of NOD-like receptor pyrin domain 3 (NLRP3) inflammasome activation, which leads to the generation of bioactive interleukin (IL)-1ß and IL-18. E74-like ETS transcription factor 3 (ELF3) participates in endothelial inflammatory processes. We hypothesized that ELF3 modulates MARK4 expression in vascular endothelial cells, thus contributing to high glucose-mediated NLRP3 inflammasome activation. Plasma IL-1ß, IL-18, NLRP3 inflammasome and MARK4 expression was increased in diabetic patients and rats. An in vitro study indicated that high glucose increased IL-1ß and IL-18 expression and activated the NLRP3 inflammasome via upregulation of MARK4 in human umbilical vein endothelial cells (HUVECs). Furthermore, high glucose increased ELF3 expression. ELF3 downregulation reversed the effects of high glucose treatment. Accordingly, the effects of ELF3 overexpression were similar to those of high glucose treatment and were counteracted by siMARK4. Furthermore, ELF3 was found to interact with SET8. High glucose inhibited SET8 expression and histone H4 lysine 20 methylation (H4K20me1), a downstream target of SET8. Overexpression of SET8 inhibited high glucose-induced MARK4 expression and NLRP3 inflammasome activation. The effects of shSET8 were similar to those of high glucose treatment and were counteracted by siMARK4. A mechanistic study found that ELF3 and H4K20me1 were enriched in the MARK4 promoter region. si-ELF3 attenuated MARK4 promoter activity and augmented the inhibitory effect of SET8 on MARK4 promoter activity. Furthermore, SET8 downregulation and ELF3 upregulation were confirmed in diabetic patients and rats. In conclusion, ELF3 interacted with SET8 to modulate MARK4 expression, which participated in hyperglycaemia-mediated endothelial NLRP3 inflammasome activation.

Fasting inhibits aerobic glycolysis and proliferation in colorectal cancer via the Fdft1-mediated AKT/mTOR/HIF1α pathway suppression.

Evidence suggests that fasting exerts extensive antitumor effects in various cancers, including colorectal cancer (CRC). However, the mechanism behind this response is unclear. We investigate the effect of fasting on glucose metabolism and malignancy in CRC. We find that fasting upregulates the expression of a cholesterogenic gene, Farnesyl-Diphosphate Farnesyltransferase 1 (FDFT1), during the inhibition of CRC cell aerobic glycolysis and proliferation. In addition, the downregulation of FDFT1 is correlated with malignant progression and poor prognosis in CRC. Moreover, FDFT1 acts as a critical tumor suppressor in CRC. Mechanistically, FDFT1 performs its tumor-inhibitory function by negatively regulating AKT/mTOR/HIF1α signaling. Furthermore, mTOR inhibitor can synergize with fasting in inhibiting the proliferation of CRC. These results indicate that FDFT1 is a key downstream target of the fasting response and may be involved in CRC cell glucose metabolism. Our results suggest therapeutic implications in CRC and potential crosstalk between a cholesterogenic gene and glycolysis.

Fasting Induces Hepatocellular Carcinoma Cell Apoptosis by Inhibiting SET8 Expression.

BACKGROUND: Hepatocellular carcinoma (HCC) is a life-threatening cancer, and the Kelch-like ECH-associated protein 1 (Keap1)/NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) signalling pathway plays a crucial role in apoptosis resistance in cancer cells. Fasting is reported to mediate tumour growth reduction and apoptosis. SET8 is involved in cancer proliferation, invasiveness, and migration. However, whether SET8 participates in fasting-mediated apoptosis in HCC remains unclear. METHODS: We used immunohistochemical staining to analyse the expression of SET8, Keap1, and Nrf2 in HCC tissues. Cell viability, apoptosis, and cellular reactive oxygen species (ROS) were assessed, and Western blot and qPCR analyses were used to examine the expression of Keap1/Nrf2 in HCC cells under fasting, SET8 overexpression, and PGC1α overexpression conditions. Mass spectrometry, coimmunoprecipitation, and confocal microscopy were used to determine whether PGC1α overexpression conditions. Mass spectrometry, coimmunoprecipitation, and confocal microscopy were used to determine whether PGC1In vivo experiments were performed to verify the conclusions from the in vitro experiments. RESULTS: Our data indicate that SET8 expression is associated with poor survival in HCC patients. Both in vitro experiments. in vivo experiments were performed to verify the conclusions from the α overexpression conditions. Mass spectrometry, coimmunoprecipitation, and confocal microscopy were used to determine whether PGC1α overexpression conditions. Mass spectrometry, coimmunoprecipitation, and confocal microscopy were used to determine whether PGC1. CONCLUSIONS: The results of our study demonstrate that fasting induces HCC apoptosis by inhibiting SET8 expression and that SET8 interacts with PGC1α to activate the Nrf2/ARE signalling pathway by inhibiting Keap1 expression.α overexpression conditions. Mass spectrometry, coimmunoprecipitation, and confocal microscopy were used to determine whether PGC1.

The disconnection technique with the use of a bronchial blocker for improving nonventilated lung collapse in video-assisted thoracoscopic surgery.

BACKGROUND: One-lung ventilation (OLV) is becoming an essential component of thoracic anesthesia. The two principal devices used for OLV are a double-lumen tube (DLT) and a bronchial blocker (BB). We hypothesized that the use of a BB with the disconnection technique would improve the quality of lung collapse in video-assisted thoracoscopic surgery (VATS). METHODS: Seventy-five patients undergoing scheduled VATS were enrolled in this study and were randomly divided into two groups: a left-sided DLT group (Group D) and a BB with the disconnection technique group (Group B). OLV was initiated when the surgeon performed the skin incision. In Group D, the left channel of the DLT was opened to the air. In Group B, the lung was deflated via the disconnection technique, thus opening the breathing circuit to the air fifteen seconds after opening the pleura. The mean arterial pressure (MAP) and heart rate (HR) during induction; the quality of lung collapse 1 and 10 minutes after pleural opening; the time required for complete lung collapse; the correct placement of the device; and the number of patients suffering from a sore throat after surgery were recorded. RESULTS: Compared with the use of the DLT, the use of the BB with the disconnection technique was associated with a similar quality of lung collapse, a comparable required time for total lung collapse (P>0.05, respectively), a lower incidence of sore throat both when leaving the PACU and 24 hours after surgery (34.2% vs. 13.5%, 15.8% vs. 5.4%, P<0.05, respectively) and fewer hemodynamic fluctuations after intubation both one and ten minutes after pleural opening. CONCLUSIONS: The use of a BB with the disconnection technique in VATS offers an effective method for improving the quality of lung collapse and reducing postoperative sore throat.

Implementation of enhanced recovery after surgery in patients undergoing radical cystectomy: A retrospective cohort study.

BACKGROUND: To evaluate the feasibility and effect of implementing enhanced recovery after surgery (ERAS) in patients undergoing radical cystectomy (RC) and urinary diversion. MATERIALS AND METHODS: Since October 2016, a 15-point ERAS protocol has been implemented for patients undergoing elective RC and urinary diversion at Fudan University Shanghai Cancer Center (FUSCC). We retrospectively assessed patients who underwent RC performed between January 2014 and June 2018. The effects of implanting ERAS for RC were validated. RESULTS: A total of 443 patients were included. The ERAS and non-ERAS groups included 185 and 258 patients, respectively. There was no significant difference in the patients' demographic characteristics, operative variables, perioperative systemic inflammation-based scores or mortality rates. Compared with the non-ERAS group, our study showed decreases in intraoperative blood loss volumes and transfusion rates in the ERAS group. Patients in the ERAS group also had earlier times to tolerate a clean liquid diet intake, first ambulation and first flatus. The incidences of postoperative pneumonia, urine leakage, intestinal obstruction and deep venous thrombosis were also significantly lower in the ERAS group. The time to pelvic drainage tube removal and the length of stay (LOS) were significantly shorter in the ERAS group than in the non-ERAS group, and the ERAS group also had a significantly lower incidence of 30-day readmission. CONCLUSIONS: The results of this study suggest that ERAS protocols can accelerate the rehabilitation of patients undergoing RC, reduce the incidence of postoperative complications, shorten the LOS, and are safe and feasible in the field of RC. This study provides experience from FUSCC to further optimize ERAS protocols for patients with bladder cancer.

Impact of perioperative red blood cell transfusion on postoperative recovery and long-term outcome in patients undergoing surgery for ovarian cancer: A propensity score-matched analysis.

BACKGROUND: The impact of perioperative red blood cell transfusion (PRBCT) on cancer survival has remained controversial. METHODS: We conducted a retrospective study in patients undergoing primary debulking surgery (PDS) for ovarian cancer between January 2013 and December 2017. The patients were divided into two groups based on whether they received PRBCT. Clinical characteristics were compared between groups. After propensity score matching, perioperative systemic inflammation-based scores, quality of recovery, postoperative outcomes, disease-free survival (DFS), and overall survival (OS) were compared between groups. Univariate and multivariable Cox proportional hazard models were used to evaluate the association between covariates and survival outcomes. RESULTS: A total of 1037 patients were enrolled in this study, and 31.7% of patients received PRBCT. After propensity matching, there was no significant difference in the clinical characteristics between groups. Patients receiving PRBCT had more postoperative fluctuations in systemic inflammatory response-related indicators (P < 0.001), a higher incidence of postoperative grade II complications (28.4% vs. 14.8%), a longer length of stay (10.6 d vs. 6.2 d) and higher 30-day and total readmission rates (7.1% vs. 4.4% and 11.2% vs. 8.1%, P < 0.001, respectively) than patients who did not receive PRBCT. The OS and DFS rates 3 years after surgery were significantly lower in the patients receiving PRBCT than in patients not receiving PRBCT (58.9% vs. 74.5%, 39.6% vs. 52.3%). CONCLUSIONS: PRBCT was significantly associated with more fluctuations in systemic inflammatory indicators, a prolonged length of stay, higher postoperative complication rates and increased cancer recurrence and overall mortality in ovarian cancer patients undergoing PDS.

Propofol attenuates the adhesion of tumor and endothelial cells through inhibiting glycolysis in human umbilical vein endothelial cells.

Propofol is one of the most commonly used intravenous anesthetics and plays an important role in tumor suppression. In the present study, we aimed to investigate the mechanism by which propofol attenuates tumor endothelial cells (TECs) and tumor cell adhesion to inhibit tumor metastasis in vitro. Human umbilical vein endothelial cells (HUVECs) cultured in Dulbecco's modified Eagle's medium were treated with tumor conditioned medium for 24 h, followed by 4 h of treatment with or without 25 µM of propofol, 10 µM of KN93, 500 µM of MK801, or 20 µM of rapastinel. It was found that propofol inhibited TEC adhesion and the glycolysis level of TECs. Consistently, propofol inhibited the expressions of adhesion molecules (E-selectin, ICAM-1, and VCAM-1) and glycolysis proteins (GLUT1, HK2, and LDHA) in TECs. Moreover, propofol attenuated the expression of HIF-1α, the phosphorylation of AKT and Ca2+/calmodulin-dependent protein kinase II (CaMKII), and the Ca2+ concentration in TECs. MK801, an inhibitor of NMDA receptor, and KN93, an inhibitor of CaMKII, both inhibited the expressions of adhesion molecules and glycolysis proteins, in a manner similar to propofol. Additionally, rapastine, an activator of NMDA receptor, could counteract the effects of propofol. Our results indicated that propofol attenuates intracellular Ca2+ concentration, CaMKII and AKT phosphorylation, and HIF-1α expression, probably via inhibiting the NMDA receptor, thus inhibiting glycolysis and adhesion of tumor and endothelial cells.