Comparing oxygen therapies for hypoxemia prevention during gastrointestinal endoscopy under procedural sedation: A systematic review and network meta-analysis.

STUDY OBJECTIVE: Hypoxemia is the most frequent adverse event observed during gastrointestinal endoscopy under procedural sedation. An optimum oxygen therapy has still not been conclusively determined. DESIGN: A systematic review and network meta-analysis of randomized clinical trials. SETTING: Digestive Endoscopy Center. PATIENTS: Adults (≥18 years old and of both sexes) during gastrointestinal endoscopy under procedural sedation. INTERVENTIONS: Pubmed, MEDLINE, Web of Science, Embase, and Clinicaltrials.gov. were searched until June 30, 2023. Randomized clinical trials (RCTs) comparing any oxygen therapy with another oxygen therapy or with placebo (nasal cannula, NC) were included. MEASUREMENT: The primary outcome was the incidence of hypoxemia, defined as the pulse oxygen saturation (SpO2). Random-effects network meta-analyses were performed. Data are reported as odds ratios (OR), prediction intervals (PrI) and 95% CI. Bias risk was evaluated following the guidelines outlined by the Cochrane Collaboration. The quality of evidence was evaluated through the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. MAIN RESULTS: We included 27 RCTs with a total of 7552 patients. Compared to the use of NC, non-invasive positive pressure ventilation (NIPPV) demonstrated superior efficacy in mitigating hypoxemia (NIPPV vs. NC, OR = 0.16, 95% CI: 0.08-0.31, 95% PrI: 0.06-0.41), followed by Wei nasal jet tube (WNJT) (WNJT vs. NC, OR = 0.17, 95% CI: 0.10-0.30, 95% PrI: 0.07-0.42). The efficacy for preventing hypoxemia was ranked as follows: NIPPV > WNJT > oropharynx/nasopharyngeal catheter > high-flow nasal oxygenation > nasal mask > NC. CONCLUSIONS: During gastrointestinal endoscopy under procedural sedation, all other advanced oxygen therapies were found to be more efficacious than nasal cannula. NIPPV and WNJT appear to be the most efficacious oxygen therapy for preventing hypoxemia. Additionally, clinicians should make a choice regarding the most suitable oxygen therapy based on the risk population, type of endoscopy and adverse events.

Upconversion-Mediated Optogenetics for the Treatment of Surgery-Induced Postoperative Neurocognitive Dysfunction.

Perioperative neurocognitive disorder (PND) is a common complication in surgical patients. While many interventions to prevent PND have been studied, the availability of treatment methods is limited. Thus, it is crucial to delve into the mechanisms of PND, pinpoint therapeutic targets, and develop effective treatment approaches. In this study, reduced dorsal tenia tecta (DTT) neuronal activity was found to be associated with tibial fracture surgery-induced PND, indicating that a neuronal excitation-inhibition (E-I) imbalance could contribute to PND. Optogenetics in the DTT brain region was conducted using upconversion nanoparticles (UCNPs) with the ability to convert 808 nm near-infrared light to visible wavelengths, which triggered the activation of excitatory neurons with minimal damage in the DTT brain region, thus improving cognitive impairment symptoms in the PND model. Moreover, this noninvasive intervention to modulate E-I imbalance showed a positive influence on mouse behavior in the Morris water maze test, which demonstrates that UCNP-mediated optogenetics is a promising tool for the treatment of neurological imbalance disorders.

Mesenchymal stem cells alleviate sepsis-induced acute lung injury by blocking neutrophil extracellular traps formation and inhibiting ferroptosis in rats.

Acute lung injury (ALI) is one of the most serious complications of sepsis, characterized by high morbidity and mortality rates. Ferroptosis has recently been reported to play an essential role in sepsis-induced ALI. Excessive neutrophil extracellular traps (NETs) formation induces exacerbated inflammation and is crucial to the development of ALI. In this study, we explored the effects of ferroptosis and NETs and observed the therapeutic function of mesenchymal stem cells (MSCs) on sepsis-induced ALI. First, we produced a cecal ligation and puncture (CLP) model of sepsis in rats. Ferrostain-1 and DNase-1 were used to inhibit ferroptosis and NETs formation separately, to confirm their effects on sepsis-induced ALI. Next, U0126 was applied to suppress the MEK/ERK signaling pathway, which is considered to be vital to NETs formation. Finally, the therapeutic effect of MSCs was observed on CLP models. The results demonstrated that both ferrostain-1 and DNase-1 application could improve sepsis-induced ALI. DNase-1 inhibited ferroptosis significantly in lung tissues, showing that ferroptosis could be regulated by NETs formation. With the inhibition of the MEK/ERK signaling pathway by U0126, NETs formation and ferroptosis in lung tissues were both reduced, and sepsis-induced ALI was improved. MSCs also had a similar protective effect against sepsis-induced ALI, not only inhibiting MEK/ERK signaling pathway-mediated NETs formation, but also alleviating ferroptosis in lung tissues. We concluded that MSCs could protect against sepsis-induced ALI by suppressing NETs formation and ferroptosis in lung tissues. In this study, we found that NETs formation and ferroptosis were both potential therapeutic targets for the treatment of sepsis-induced ALI, and provided new evidence supporting the clinical application of MSCs in sepsis-induced ALI treatment.

E2F1-mediated Up-regulation of NCAPG Promotes Hepatocellular Carcinoma Development by Inhibiting Pyroptosis.

Background and Aims: As a subunit of the condensin complex, NCAPG has an important role in maintaining chromosome condensation, but its biological function and regulatory mechanism in hepatocellular carcinoma (HCC) remains undefined. Methods: The prognostic ability of NCAPG in HCC patients was examined by univariate and multivariate Cox regression analysis. ROC curves were plotted to compare the predictive ability of NCAPG and AFP. Double luciferase reporter system, and ChIP were used to investigate transcriptional potential of E2F1 to NCAPG. Pyroptosis was observed by scanning electron microscopy. Protein expression of NCAPG, E2F1, and major proteins constituting NLRP3 inflammasome was determined by western blotting and ELISA. An in vivo tumor formation assay was conducted to verify the in vitro results. Results: Up-regulated NCAPG was identified in HCC tissues compared with adjacent tissue and high NCAPG was positively correlated with poor prognosis. Serum NCAPG mRNA level was a prognostic factor in HCC patients and also a diagnostic factor with higher predictive ability compared with AFP [AUROC 0.766 (95% CI: 0.650-0.881) vs. 0.649 (95% CI 0.506-0.793)]. HBx transfection resulted in concomitant up-regulation of E2F1 and NCAPG. E2F1 significantly increased the activity of luciferase reporter fused with NCAPG reporter, and the interaction of E2F1 and NCAPG gene was confirmed by ChIP. Silencing of E2F1 resulted in significant down-regulation of NCAPG. Knockdown of NCAPG promote pyroptosis mediated by NLRP3 inflammasome activation in multiple HCC cell lines and also suppressed tumorigenesis in vitro. Conclusions: We identified a novel role of NCAPG in the regulation of NLRP3 inflammasome-mediated pyroptosis, which was regulated by its upstream transactivator, E2F1. The role of E2F1-NCAPG-NLRP3 regulation of pyroptosis network may be a potential target in HCC treatment.

Effect of Esketamine Gargle on Postoperative Sore Throat in Patients Undergoing Double-Lumen Endobronchial Intubation: A Randomised Controlled Trial.

Background: Postoperative sore throat is a frequent adverse event after double-lumen endobronchial tube (DLT) intubation. The aim of this study was to investigate whether esketamine gargle has a preventive effect on the incidence of postoperative sore throat in patients undergoing DLT intubation. Methods: This trial included 140 patients undergoing elective thoracic surgery at the third affiliated hospital of Sun Yat-Sen University. Patients were randomly allocated into the following two groups of 70 patients each: the control group, gargling with saline of 30 mL, and the esketamine group, gargling with an esketamine solution of 30 mL (2 mL/50 mg esketamine in 28 mL saline), 5 min prior to anaesthesia induction. The primary outcome was the incidence of sore throat 24 h after surgery. The main secondary outcomes included the incidence of sore throat and hoarseness at 1 h and 48 h after surgery, as well as the intraoperative haemodynamic responses. Results: The incidence of sore throat was significantly higher in the control group (47.1%, 33/70 patients) compared with the esketamine group (12.9%, 9/70 patients) at 24 h after surgery (RD, 0.41; 95% confidence interval, 0.26-0.57; p < 0.001). Furthermore, the incidence of sore throat at 1 h (p = 0.027), 24 h (p = 0.019), and seventh day (p = 0.031) as well as hoarseness at 1 h (p = 0.027), 24 h (p = 0.019), and 48 h (p = 0.031) after surgery were reduced in the esketamine group. Significant differences were seen in the peak levels of systolic blood pressure, mean arterial blood pressure, and heart rate between the groups during the intubation (p < 0.05). Besides, no patient developed an adverse reaction to esketamine. Conclusion: Preoperative gargling of esketamine can provide an effect against sore throat after DLT intubation without adverse side effects and effectively inhibit sharp elevations in heart rate and blood pressure during double-lumen intubation procedures.

Effect of an educational video about ERAS on reducing preoperative anxiety and promoting recovery.

Video propaganda is reported effectively improving patients' understanding of operation. However, whether a video introducing patients' most concerns can reduce preoperative anxiety and promote recovery stays unsealed. In this study, we investigated the effects of complementary therapy of educational video during preoperative visit. The results showed that thirty-five (23.2%) parents in Group Control were diagnosed as anxiety according to SAS, and nineteen (12.3%) patients were diagnosed after video intervention. The APAIs anxiety score and APAIs information score in Group Video were lower than those in Group Control. Compared with Group Control, video visit helped to increase the first-attempt pass rate of the knowledge retention exam and solve the patient's most worried concerns, and decrease incidence of emergence agitation, total cost of hospitalization and length of hospital stay. Moreover, video visit improved satisfaction degrees of patients and their main family members. Briefly, our study demonstrated video visit can improve patients' knowledge of anesthesia and decrease their preoperative anxiety, which may represent an important complementary therapy to routine preoperative visits.

5-aminolevulinate and CHIL3/CHI3L1 treatment amid ischemia aids liver metabolism and reduces ischemia-reperfusion injury.

Rationale: Liver resection and transplantation surgeries are accompanied by hepatic ischemia-reperfusion (HIR) injury that hampers the subsequent liver recovery. Given that the liver is the main organ for metabolism and detoxification, ischemia-reperfusion in essence bestows metabolic stress upon the liver and disrupts local metabolic and immune homeostasis. Most of the recent and current research works concerning HIR have been focusing on addressing HIR-induced hepatic injury and inflammation, instead of dealing with the metabolic reprogramming and restoration of redox homeostasis. As our previous work uncovers the importance of 5-aminolevulinate (5-ALA) synthesis during stress adaptation, here we evaluate the effects of supplementing 5-ALA to mitigate HIR injury. Methods: 5-ALA was supplemented into the mice or cultured cells during the ischemic or oxygen-glucose deprivation (OGD) phase. Following reperfusion or reoxygenation, cellular metabolism and energy homeostasis, mitochondrial production of reactive oxygen species (ROS) and transcriptomic changes were evaluated in HIR mouse models or cultured hepatocytes and macrophages. Liver injury, hepatocytic functional tests, and macrophagic M1/M2 polarization were assessed. Results: Dynamic changes in the expression of key enzymes in 5-ALA metabolism were first confirmed in donor and mouse liver samples following HIR. Supplemented 5-ALA modulated mouse hepatic lipid metabolism and reduced ATP production in macrophages following HIR, resulting in elevation of anti-inflammatory M2 polarization. Mechanistically, 5-ALA down-regulates macrophagic chemokine receptor CX3CR1 via the repression of RelA following OGD and reoxygenation (OGD/R). Cx3cr1 KO mice demonstrated milder liver injuries and more macrophage M2 polarization after HIR. M2 macrophage-secreted chitinase-like protein 3 (CHIL3; CHI3L1 in human) is an important HIR-induced effector downstream of CX3CR1 deficiency. Addition of CHIL3/CHI3L1 alone improved hepatocellular metabolism and reduced OGD/R-inflicted injuries in cultured mouse and human hepatocytes. Combined treatment with 5-ALA and CHIL3 during the ischemic phase facilitated lipid metabolism and ATP production in the mouse liver following HIR. Conclusion: Our results reveal that supplementing 5-ALA promotes macrophagic M2 polarization via downregulation of RelA and CX3CR1 in mice following HIR, while M2 macrophage-produced CHIL3/CHI3L1 also manifests beneficial effects to the recovery of hepatic metabolism. 5-ALA and CHIL3/CHI3L1 together mitigate HIR-induced mitochondrial dysfunction and hepatocellular injuries, which may be developed into safe and effective clinical treatments to attenuate HIR injuries.

Preoperative hs-CRP/HDL ratio is associated with increased risk for postoperative SIRS in elderly patients: a retrospective cohort study.

BACKGROUND: Systemic inflammatory response syndrome (SIRS) greatly affects postoperative lives of afflicted aged patients. This study aimed to determine whether preoperative high hs-CRP/HDL ratio (CHR) was associated with an increased risk of postoperative SIRS in the elderly population. METHODS: This retrospective cohort study included data on patients aged ≥ 65 years who underwent general anesthesia surgery at two clinical centers between January 2015 and September 2020. The primary exposure was preoperative CHR which was divided into two groups (≤ 12.82 and > 12.82) based on its normal range in our hospital, and the primary outcome was the incidence of postoperative SIRS. Targeted maximum likelihood estimation analyses were used to model the exposure-outcome relationship. RESULTS: The analysis included 5595 elderly patients, of whom 1410 (25.20%) developed SIRS within three postoperative days. Targeted maximum likelihood estimation analysis revealed that elderly patients with CHR > 12.82 vs. CHR ≤ 12.82 was associated with increased risk of postoperative SIRS (aOR = 1.40, 95% CI [1.33, 1.48], P < 0.001). Those results were consistent both in subgroup analyses and sensitivity analyses. Compared with patients with CHR ≤ 12.82, patients with CHR > 12.82 had a higher prevalence of postoperative SIRS (49.06% vs. 22.70%), postoperative in-hospital mortality (3.40% vs. 0.65%), a longer hospital stay after surgery [10 (IQR, 6-16) vs. 8 (IQR, 5-11) days] and higher direct medical cost [10070 (IQR, 6878-15577) vs. 7117 (IQR, 4079-10314) euros, all P < 0.001]. CONCLUSIONS: In elderly patients, preoperative CHR > 12.82 was significantly associated with a higher risk of postoperative SIRS.

Dual-regulation by Cx32 in hepatocyte to trigger and worsen liver graft injury.

Liver transplantation is the ultimate treatment option for end-stage liver failure. However, liver graft injury remains a challenge. This study aimed to investigate the role of connexin32 (Cx32) in liver graft injury and elucidate its mechanism of action. Through detecting liver graft samples from 6 patients, we observed that changes in the Cx32 level coincided with liver graft injury. Therefore, we established autologous orthotopic liver transplantation (AOLT) models using Cx32-knockout and wild-type mice and hypoxia/reoxygenation (H/R) and lipopolysaccharide (LPS) pretreatment models using alpha mouse liver 12 (AML12) cells, to explore Cx32 mechanisms in liver graft injury. Following in vivo and in vitro Cx32 knockout, oxidative stress and inflammatory response were inhibited through the regulation of PKC-α/NF-κB/NLRP3 and Nrf2/NOX4/ROS signaling pathways, thereby reducing Bak/Bax-related apoptosis and ameliorating liver graft injury. When the Cx32-based gap junction (GJ) was blocked with 2-aminoethoxydiphenyl borate (2-APB), ROS transfer was attenuated between neighboring cells, exacerbated oxidative stress and inflammatory response were prevented, and aggravation of liver graft injury was mitigated. These results highlight the dual regulation mechanism of Cx32 in liver graft injury. Through interaction with PKC-α, Cx32 regulated the NF-κB/NLRP3 and Nrf2/NOX4/ROS signaling pathways, thus directly triggering oxidative stress and inflammatory response. Simultaneously, mass-produced ROS were transferred to neighboring cells through Cx32 channels, for which oxidative stress and the inflammatory response were aggravated indirectly. Finally, Bak/Bax-related apoptosis was activated, thereby worsening liver graft injury. Our findings propose Cx32 as a dual mechanistic factor for oxidative stress and inflammatory signaling pathways in regulating cell apoptosis on liver graft injury, which suggests a promising therapeutic targets for liver graft injury.

Modified Manual Chest Compression for Prevention and Treatment of Respiratory Depression in Patients Under Deep Sedation During Upper Gastrointestinal Endoscopy: Two Randomized Controlled Trials.

BACKGROUND: We aimed to determine the preventive and therapeutic efficacy of modified manual chest compression (MMCC), a novel noninvasive and device-independent method, in reducing oxygen desaturation events in patients undergoing upper gastrointestinal endoscopy under deep sedation. METHODS: A total of 584 outpatients who underwent deep sedation during upper gastrointestinal endoscopy were enrolled. In the preventive cohort, 440 patients were randomized to the MMCC group (patients received MMCC when their eyelash reflex disappeared, M1 group) or control group (C1 group). In the therapeutic cohort, 144 patients with oxygen desaturation of a Sp o2 < 95% were randomized to MMCC group (patients who subsequently received MMCC, M2 group) or the conventional treatment group (C2 group). The primary outcomes were the incidence of desaturation episodes with an Sp o2 < 95% for the preventive cohort and the time spent below 95% Sp o2 for the therapeutic cohort. Secondary outcomes included the incidence of gastroscopy withdrawal and diaphragmatic pause. RESULTS: In the preventive cohort, MMCC reduced the incidence of desaturation episodes <95% (14.4% vs 26.1%; RR, 0.549; 95% confidence interval [CI], 0.37-0.815; P = .002), gastroscopy withdrawal (0% vs 2.29%; P = .008), and diaphragmatic pause at 30 seconds after propofol injection (74.5% vs 88.1%; RR, 0.846; 95% CI, 0.772-0.928; P < .001). In the therapeutic cohort, patients who received MMCC had a significantly shorter time spent below 95% Sp o2 (40 [20-69] seconds vs 91 [33-152] seconds, median difference [95% CI], -39 [-57 to -16] seconds, P < .001), a lower incidence of gastroscopy withdrawal (0% vs 10.4%, P = .018), and more enhanced diaphragmatic movement at 30 seconds after Sp o2 <95% (1.11 [0.93-1.4] cm vs 1.03 [0.7-1.24] cm; median difference [95% confidence interval], 0.16 [0.02-0.32] cm; P = .015). CONCLUSIONS: MMCC may exert preventive and therapeutic effects against oxygen desaturation events during upper gastrointestinal endoscopy.

WITHDRAWN: The Analgesic Effect of Regional Blocks for Modified Radical Mastectomy: A Network Meta-analysis.

Ahead of Print article withdrawn by publisher.

Bone marrow-derived mesenchymal stem cells attenuate complete Freund's adjuvant-induced inflammatory pain by inhibiting the expression of P2X3.

Bone marrow-derived mesenchymal stem cells (BMSCs) show a good property for pain treatment by modulating inflammatory response. However, the underlying therapeutic effect and related mechanism of BMSCs on inflammatory pain remain unclear. Therefore, we explored the function and potential mechanism of BMSCs performing in a complete Freund's adjuvant (CFA)-induced inflammatory pain model in this study. Here, BMSCs were injected into the CFA-treated rats, and we used behavioural tests to evaluate the changes in hypersensitivity. High-throughput sequencing was used to screen out the hub genes. Molecular biology experiments were performed to detect the level of P2X3 or inflammatory mediators in rats and observed the distribution of P2X3 in neural cells. Furthermore, the function of the P2X3 was explored via inhibitor and activator experiments. Finally, we found that BMSCs alleviated hyperalgesia and spinal levels of pro-inflammatory factors in CFA-treated rats. High-throughput sequencing showed that P2X3 and P2X7 were identified as hub genes, and only the expression level of P2X3 was significantly down-regulated after BMSCs treatment. Immunohistochemistry showed that P2X3 mainly colocalized with microglia and astrocytes. The levels of P2X3 and pro-inflammatory factors were all significantly reduced after BMSC injection. Moreover, similar attenuation was found in the CFA-treated rats after injecting the P2X3 inhibitor, and a P2X3 antagonist reversed the attenuation induced by the BMSCs. These findings suggest that BMSCs exerted a therapeutic effect on inflammatory pain by inhibiting the expression of P2X3 and the excessive production of inflammatory mediators was associated with an increased P2X3 level and BMSC therapy reverse these effects.

Functional analysis of hepatic long non-coding ribonucleic acids during liver transplantation in humans.

BACKGROUND: The potential function of long non-coding RNAs (lncRNAs) in human hepatic ischemia-reperfusion injury (HIRI) remains to be clarified. METHODS: Clinical samples of transplanted liver tissues from 26 patients undergoing liver transplantation (LT) and normal liver tissues from seven patients undergoing hepatic hemangiomactomy (Con) were collected. Typical samples were subjected to whole transcriptome sequencing (RNA-seq). Differentially expressed genes between groups were identified by DEGseq and were analyzed by enrichment analysis including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis. Transcription of five lncRNAs including NONHSAG039942, NONHSAG071405, NONHSAG027516, LXLOC_058190, and LXLOC_024376 that presented significant difference in RNA-sequencing were validated by a quantitative real-time PCR (qRT-PCR), for which the subcellular localization and the binding ability to known human RNA-binding proteins (RBPs) were respectively predicted by LncLocator and catRAPID genomics v2.1. RESULTS: We identified 2917 lncRNAs and 2811 mRNAs that were differentially expressed (p < 0.05 and log2 fold change > 1 or < -1) between groups (LT vs. Con). NONHSAG039942, NONHSAG071405, LXLOC_058190, and LXLOC_024376 were validated by qRT-PCR to be significantly increased in the LT group, and were all predicted to be localized in cytoplasm or cytosol. NONHSAG039942, NONHSAG071405, and LXLOC_058190 held an RBP interaction propensity score of 98.07%, 76.95%, and 152.99%, respectively, with heterogeneous-nuclear ribonucleoprotein U (HNRNPU). Pathways significantly activated in transplant livers that involved HNRNPU as a core enrichment gene included hypoxia, ACE2 expression, apoptosis, spliceosome formation, etc. CONCLUSIONS: NONHSAG039942, NONHSAG071405, and LXLOC_058190 were significantly increased in transplant livers after reperfusion and their role in HIRI may be associated with HNRNPU, a core protein that participates in hypoxia and chromatin accessibility.

Bilevel positive airway pressure for gastroscopy with sedation in patients at risk of hypoxemia: A prospective randomized controlled study.

STUDY OBJECTIVE: Hypoxemia is one of the most frequent adverse events during sedated gastroscopy, and there is still no effective means to prevent and cure it. Therefore, we conducted this randomized trial to confirm our hypothesis that, compared with the nasal cannula group, bilevel positive airway pressure (BPAP) would decrease the incidence of hypoxemia in patients with obstructive sleep apnea (OSA) or overweight status undergoing gastroscopy. DESIGN: In a single-center, prospective, randomized controlled clinical trial, 80 patients aged 18-65 years and with OSA or overweight status who underwent gastroscopy with sedation were randomly assigned to two groups: the nasal cannula and BPAP groups. The primary outcome was the incidence of hypoxemia (75% < peripheral oxygen saturation [SpO2] < 90% for >5 sand <60 s). MAIN RESULTS: Compared to the nasal cannula group, BPAP therapy significantly decreased the incidence of hypoxemia from 40.0% to 2.5% (absolute risk difference [ARD], 37.5% [95% confidence interval (CI), 21.6 to 53.4], p < 0.001), decreased subclinical respiratory depression from 52.5% to 22.5% (ARD, 30.0% [95% CI, 9.8 to 50.2], p = 0.006), and decreased severe hypoxemia from 17.5% to 0% (ARD, 17.5% [95% CI, 5.7 to 29.3], p = 0.006). The BPAP intervention also decreased the total propofol dosage and operation time and improved anesthesiologist's satisfaction. CONCLUSION: BPAP therapy significantly decreased the incidence of hypoxemia in patients with OSA or overweight status who underwent gastroscopy.

Classification of colorectal cancer into clinically relevant subtypes based on genes and mesenchymal cells.

BACKGROUND: Most studies on subtype identification of colorectal cancer (CRC) were based on expressions of either genes or immune cells. However, few studies have hitherto used the combination of genes with immune and stroma cells for subtype identification. METHODS: Dataset GSE17536 was obtained from the Gene Expression Omnibus (GEO) database. The xCell algorithm was used to estimate the composition and density of 64 cell types, including immune and stroma cell types. Clustering analysis was then conducted on the top 3000 most variable genes from a total of 20,174 genes for CRC subtype identification. We employed the ensemble method of Similarity network fusion and 112 Consensus Clustering (SNF-CC) for cancer subtype identification. Reactome pathway analysis was conducted to identify the impact of the representative genes on prognosis. The results were validated in independent gene expression data from dataset GSE17537. RESULTS: In this study, we identified 3 clinically relevant subtypes and their representative genes, immune and stroma cells. Moreover, we confirmed the correlation of these subtypes with their clinical characteristics. The representative genes of the subtype with poor prognosis correlated with extracellular matrix structural constituent, while the subtype with good prognosis correlated with Toll-like receptor signaling pathway or chemokine signaling pathway. However, different subtypes were associated with distinct cell subtypes; the subtype with poor prognosis had a high abundance of fibroblasts and endothelial cells; the subtype with median prognosis had a higher abundance of immune cells, such as CD4 + T-cell, Th2 cells and aDC; the subtype with good prognosis had a higher abundance of NKT. CONCLUSION: This study highlights the utility of immune and innate cells, especially during gene analysis, to provide the theoretical basis for personalized treatment in colorectal cancer patients.

Hypertriglyceridemia is associated with stroke after non-cardiac, non-neurological surgery in the older patients: A nested case-control study.

Introduction: Geriatric postoperative stroke is a rare but serious complication after surgery. The association between hypertriglyceridemia and postoperative stroke remains controversial, especially in older patients undergoing non-cardiac, non-neurological surgery. The study aims to address this clinical dilemma. Materials and methods: We conducted a nested case-control study among 9601 aged patients undergoing non-cardiac non-neurological surgery from October 2015 to 2021. A total of 22 positive cases were matched for the surgical type and time, to 88 control patients by a ratio of 1:4. The effect of hypertriglyceridemia on the occurrence of postoperative stroke within 30 days after surgery was estimated using conditional logistic regression analysis by adjusting to various potential confounders. Results: A total of 22 cases developed ischemia stroke after surgery, and compared with the non-stroke group, they had more postoperative ICU admission, longer postoperative hospitalization and higher total cost (all p < 0.05), and more patients were presenting with preoperative hypertriglyceridemia [8 (36.4%) vs. 15 (17.0%), p = 0.045]. There was a significant association between hypertriglyceridemia and postoperative stroke, with adjusted odds ratios of 6.618 (95% CI 1.286, 34.064) (p = 0.024). The above results remained robust in the sensitivity analyses. Conclusion: Among older patients undergoing non-cardiac and non-neurological surgery, hypertriglyceridemia was associated with significant increased risk of postoperative stroke.

Tree-based, two-stage risk factor analysis for postoperative sepsis based on Sepsis-3 criteria in elderly patients: A retrospective cohort study.

Background: Sepsis remains the leading cause of postoperative death in elderly patients and is defined as organ dysfunction with proven or suspected infection according to Sepsis-3 criteria. To better avoid potential non-linear associations between the risk factors, we firstly used a tree-based analytic methods to explore the putative risk factors of geriatric sepsis based on the criteria in the study. Methods: Data of 7,302 surgical patients aged ≥ 65 years at the Third Affiliated Hospital of Sun Yat-sen University from January 2015 to September 2020 were collected. An analytic method that combined tree-based analysis with the method of Mantel-Haenszel and logistic regression was adopted to assess the association between 17 putative risk factors and postoperative sepsis defined by the Sepsis-3 guideline by controlling 16 potential confounding factors. Results: Among the 16 potential covariates, six major confounders were statistically identified by the tree-based model, including cerebrovascular diseases, preoperative infusion of red blood cells, pneumonia, age ≥ 75, malignant tumor and diabetes. Our analysis indicated that emergency surgery increases the risk of postoperative sepsis in elderly patients by more than six times. The type of surgery is also a crucial risk factor for sepsis, particularly transplantation and neurosurgery. Other risk factors were duration of surgery > 120 min, administration of steroids, hypoalbuminemia, elevated creatinine, blood urea nitrogen, hematocrit, platelets, glucose, white blood cell count, abnormal neutrophil-to-lymphocyte ratio and elevated hsCRP-to-albumin ratio. Conclusions: Our study uses an effective method to explore some risk factors for postoperative sepsis in elderly by adjusting many potential confounders and it can provide information for intervention design.

Right displacement of trachea to reduce right bronchial misplacement of left double lumen tube: a prospective, double-blind, randomized study.

BACKGROUND: Misplacement of double-lumen endobronchial tubes (DLTs) during bronchial intubation, especially when bronchoscopy guidance is not applicable, threatens effective lung isolation and brings about airway injury during reposition. We aimed to examine whether a novel maneuver called right tracheal displacement (RTD) can reduce left-sided DLT misplacement during first-attempt intubation without bronchoscopy guidance. METHODS: Patients that underwent thoracic surgeries requiring one-lung ventilation during November 2020 to January 2021 were recruited and randomized into control and RTD group, with 54 cases in each group. The primary outcomes included the incidence of DLT misplacement and the time to complete desired bronchial intubation. The secondary outcomes included mucosal injury, sore throat and hoarseness upon emergence and at 24 h post-operatively. RESULT: The incidence of DLT misplacement in RTD group was significantly lower compared to control group (0% vs. 16.7%) The time to complete bronchial intubation was also significantly shortened in RTD group compared to control (52.88 ± 9.36 s vs. 63.04 ± 20.02 s). The incidence of mucosal injury, sore throat and hoarseness were comparable between two groups. CONCLUSION: RTD maneuver can effectively improve the success rate of first-attempt proper DLT positioning and shorten the time required by bronchial intubation. TRIAL REGISTRATION: This prospective, double-blind, randomized study has completed the registration of the Chinese Clinical Trial Center at 2/11/2020 with the registration number ChiCTR2000040212. It was conducted from 26/11/2020 to 31/7/2021 in third affiliated hospital of Sun Yat-sen university.

Perioperative administration of methylprednisolone was associated with postoperative pulmonary complications in elderly patients undergoing hip fracture surgery.

BACKGROUND: Postoperative pulmonary complications (PPCs) seriously affect the postoperative prognosis of elderly patients underwent hip fracture surgery. Although methylprednisolone is increasingly used, the association between perioperative methylprednisolone and PPCs is still controversial. The study aims to determine whether perioperative administration of methylprednisolone is associated with PPCs in elderly patients during hip fracture surgery. PATIENTS AND METHODS: In this retrospective cohort study, records of 584 patients (≥ 65 years) who underwent hip fracture surgery between January 2013 and October 2020 were extracted. Univariate and multivariate regression analysis were performed to identify the risk factors for PPCs. To further explore the association between administration of methylprednisolone and PPCs, 53 patients received methylprednisolone and 53 patients without methylprednisolone were matched for the confounding factors using propensity score matching (PSM) analysis. The odds ratios (OR) and 95% confidence intervals (CI) for the above variables were analyzed. RESULTS: The incidence of PPCs during postoperative hospitalization was 6.83% (38/556) among the elderly patients following hip fracture surgery. Patients with PPCs had higher postoperative mortality rate, longer hospital stay, more hospitalization cost, and higher incidence of cardiac arrest (all P < 0.05). Multivariate logistic regression analysis showed that age, hypertension, hypoglycemia, hypoproteinemia and perioperative methylprednisolone were independent risk factors for PPCs. Moreover, administration of methylprednisolone was significantly correlated with PPCs both before PSM adjustment (OR = 3.25; 95% CI, 1.67 to 6.33; P = 0.001) and after PSM adjustment (OR = 6.68; 95% CI, 1.40 to 31.82; P = 0.017). CONCLUSION: Perioperative administration of methylprednisolone is a risk factor for PPCs in elderly patients undergoing hip fracture surgery.

Inhibition of the NADPH Oxidase Pathway Reduces Ferroptosis during Septic Renal Injury in Diabetic Mice.

Background: Obesity and type 2 diabetes mellitus (DM) contribute to a higher mortality rate in patients with septic acute kidney injury (AKI) during sepsis. Reactive oxygen species (ROS) is the major injury factor for sepsis. This study was aimed at exploring the potential therapeutic drug for septic AKI targeting on ROS. Methods: A murine septic AKI model was established in both wild-type and high-fat diet-fed (HFD) mice. NADPH oxidase inhibitor Vas2870 was used in vivo to explore the role of NADPH oxidase in ROS release in septic AKI in diabetic mice. Ferrostatin-1 was administered to investigate the role of ferroptosis in ROS accumulation during NADPH oxidase activating in septic AKI in diabetic mice. Results: Compared to chow diet-fed mice, HFD diabetic mice which were subjected to LPS exhibited aggravated renal function (blood urea nitrogen, creatinine clearance, and serum cystatin C) and oxidative stress (malondialdehyde, 4-HNE, ROS, 8-OHdG, and NADPH oxidase), thus resulting in a higher mortality rate. Septic renal injury was significantly attenuated by the ferroptosis inhibitor Fer-1 in HFD-challenged mice. Furthermore, ferroptosis accumulation and related protein expression (ASCL4, FTH1, and GPX4) were altered by LPS stimulation in HFD-challenged mice and suppressed by NADPH oxidase inhibition via Vas2870 in vivo. In summary, NADPH inhibition restored septic renal function from injury by suppressing ferroptosis accumulation in HFD-challenged mice. Conclusion: These results suggest that targeting NADPH-mediated ROS release and ferroptosis accumulation is a novel therapeutic strategy to protect the kidney from septic injury in patients with obesity and type 2 DM.