Oxidative balance score: a potential tool for reducing the risk of colorectal cancer and its subsites incidences.

Background: The Oxidative Balance Score (OBS) is commonly used to assess oxidative stress and provides a comprehensive evaluation of dietary and lifestyle-related exposures. However, there is limited research on the association between OBS and colorectal cancer (CRC), its subsites, and complications. The objective of this study was to assess the relationship between OBS and the risk of CRC, its subsites, and common complications in a large prospective cohort study. Methods: We included data from 175,808 participants in the UK Biobank data sample repository from 2006 to 2010. We evaluated OBS using a scoring system based on 22 dietary and lifestyle factors. Multiple adjustments, including multivariate Cox proportional hazard regression, gender stratification, subgroup analysis, and sensitivity analysis, were performed to fully explore the relationship between OBS and CRC, its subsites, and complications. The mediation analysis was conducted to investigate whether serum albumin, uric acid, and neutrophil levels mediate the relationship between OBS and CRC. Results: After adjusting for potential confounding factors, a significant negative correlation was found between OBS and the risk of CRC and its subsites (proximal colon cancer, distal colon cancer, and rectal cancer). This correlation was particularly pronounced in male CRC patients. Serum albumin, uric acid, and neutrophil count, which are biomarkers, were found to have a significant mediating effect between OBS and CRC. Conclusion: Our study suggests that higher exposure to antioxidants assessed through OBS (diet and lifestyle rich in antioxidants) may decrease the occurrence of CRC and its subsites.

Brain imaging derived phenotypes: a biomarker for the onset of inflammatory bowel disease and a potential mediator of mental complications.

Background and aims: Inflammatory bowel disease (IBD), mainly categorized into Crohn's disease (CD) and ulcerative colitis (UC), is a chronic relapsing gastrointestinal disorder that significantly impairs patients' quality of life. IBD patients often experience comorbidities such as anxiety and depression, and the underlying mechanisms and treatment strategies remain areas of investigation. Methods: We conducted a Mendelian randomization(MR) analysis utilizing brain image derived phenotypes (IDP) from the UK Biobank database to investigate the causal relationships between IBD and alterations in brain structural morphology and connectivity of neural tracts. This study aimed to identify biological evidence linking IBD to psychiatric disorders such as anxiety and depression. Results: Specifically, the volume of grey matter in the Left Frontal Orbital Cortex exhibited a negative association with the onset of Crohn's disease (odds ratio (OR) [95% confidence interval (CI)]: 0.315[0.180~0.551], adjusted P=0.001), while the volume of the superior frontal cortex in the right hemisphere showed a positive correlation with the development of Ulcerative colitis (OR [95% CI]: 2.285[1.793~2.911], adjusted P<0.001), and the volume of lateral occipital cortex in the left hemisphere demonstrated a positive relationship with Crohn's disease onset (OR [95% CI]: 1.709[1.671~1.747], adjusted P<0.001). In the context of reverse causality, the onset of UC or CD has led to alterations in imaging derived phenotypes associated with five disorders (anxiety, depression, schizophrenia, bipolar disorder, pain) and three functions (memory, emotion, language). Conclusion: Our study has demonstrated a causal relationship between IBD and IDPs. IDPs may serve as potential biomarkers for the progression of IBD and as predictive intermediaries for the development of neurological diseases in IBD patients.

High ligation versus low ligation of the inferior mesenteric artery in laparoscopic rectal cancer surgery: a retrospective study on surgical and long-term outcome.

BACKGROUND: In laparoscopic low anterior resection for rectal cancer surgery, there has been controversy to whether the inferior mesenteric artery (IMA) should be ligated at the origin of its aorta (high ligation (HL)) or below the branches of the left colonic artery (LCA) (low ligation (LL)). This study was intended to clarify oncological outcome and long-term prognosis of retrospective analysis. METHODS: Analyzed the cases who underwent laparoscopic low anterior resection (LAR) in Shanghai Ruijin Hospital from January 2015 to December 2016, 357patients scheduled into 2 groups according to the level of IMA ligation: HL (n = 247) versus LL (n = 110). RESULTS: The primary endpoint is long-term outcomes, and the secondary endpoint is the incidence rate of major postoperative complications. There were no significant differences in 5-year overall survival (P = 0.92) and 5-year disease-free survival (P = 0.41). There were no differences between the clinical baseline levels in each group. The incidence of low anterior resection syndrome (LARS) in the two groups was statistically significant (P = 0.037). No significant differences were observed in operative time (P = 0.092) and intraoperative blood loss (P = 0.118). In the HL group, 6 cases (2.4%) had additional colonic excision due to poor anastomotic blood supply; none of the colonic anastomosis in the low ligation group had ischemic manifestations, and length from the proximal margin (P = 0.076), length from the distal margin (P = 0.184), the total number of lymph nodes excised (P = 0.065), and anastomotic leakage incidence (P = 0.33). CONCLUSION: Low ligation of the IMA which reserved LCA with vascular root lymph node dissection in laparoscopic low anterior resection for rectal cancer surgery may help protect the blood supply of the anastomosis, and will not increase postoperative complications while enhance recovery, without compromising radical excision and long-term prognosis.

Intracorporeal versus extracorporeal anastomosis in laparoscopic right colectomy: a retrospective study.

BACKGROUND: The surgical procedure for laparoscopic right colectomy (LRC) is not standardized. Some published studies show the superiority of ileocolic anastomosis (IIA), but the evidence so far is insufficient. This study aimed to investigate the potential advantages in postoperative recovery and safety of IIA in LRC. METHODS: A total of 114 patients who underwent LRC with IIA (n = 58) or extracorporeal ileocolic anastomosis (EIA, n = 56) between January 2019 and September 2021 were enrolled. We collected certain factors as clinical features, intraoperative characteristics, oncological outcomes, postoperative recovery, and short-term outcomes. Our primary outcome was time to gastrointestinal (GI) function recovery. Secondary outcomes were postoperative complications within 30 days, postoperative pain, and length of hospital stay. RESULTS: Faster GI recovery and less postoperative pain were observed in patients with IIA compared to EIA [time to first flatus: (2.4 ± 0.7) vs (2.8 ± 1.0) days, p < 0.01; time to liquid intake: (3.5 ± 0.7) vs (4.0 ± 1.1) days, p = 0.01; postoperative visual analogue scale score: (3.9 ± 1.0) vs (4.3 ± 0.6), p = 0.02]. No significant differences were detected in oncological outcomes or postoperative complications. IIA, rather than EIA, tended to be performed in patients with higher body mass index [(23.93 ± 3.52) vs (22.36 ± 2.87) kg/m2, p = 0.01]. CONCLUSIONS: IIA is associated with faster GI function recovery and less postoperative pain and may be more favorable for obese patients.

FOXD1 promotes chemotherapy resistance by enhancing cell stemness in colorectal cancer through ß­catenin nuclear localization.

Forkhead box D1 (FOXD1) serves a critical role in colorectal cancer (CRC). FOXD1 expression is an independent prognostic factor in patients with CRC; however, the molecular mechanism and signaling pathway of FOXD1 that regulates cell stemness and chemoresistance has not been fully characterized. The aim of the present study was to further validate the effect of FOXD1 on the proliferation and migration of CRC cells, and to delve into the possible potential of FOXD1 in the clinical treatment of CRC. The effect of FOXD1 on cell proliferation was assessed using Cell Counting Kit 8 (CCK­8) and colony formation assays. The effect of FOXD1 on cell migration was assessed by wound­healing and Transwell assays. The effect of FOXD1 on cell stemness was assessed by spheroid formation in vitro and limiting dilution assays in vivo. The expression of stemness associated proteins, leucine rich repeat containing G protein­coupled receptor 5 (LGR5), OCT4, Sox2 and Nanog, and epithelial­mesenchymal transition associated proteins, E­cadherin, N­cadherin and vimentin, were detected by western blotting. Proteins interrelationships were assessed by a co­immunoprecipitation assay. Oxaliplatin resistance was assessed using CCK­8 and apoptosis assays in vitro, and using a tumor xenograft model in vivo. By constructing FOXD1 overexpression and knockdown stably transfected strains of colon cancer cells, it was revealed that the overexpression of FOXD1 increased CRC cell stemness and chemoresistance. By contrast, knockdown of FOXD1 produced the opposite effects. These phenomena were caused by the direct interaction between FOXD1 and ß­catenin, thus promoting its nuclear translocation and the activation of downstream target genes, such as LGR5 and Sox2. Notably, inhibition of this pathway with a specific ß­catenin inhibitor (XAV­939) could impair the effects induced by the overexpression of FOXD1. In summary, these results indicated that FOXD1 may promote cell stemness and the chemoresistance of CRC by binding directly to ß­catenin and enhancing ß­catenin nuclear localization; therefore, it may be considered a potential clinical target.

Cytokine concentration in peripheral blood of patients with colorectal cancer.

Introduction: The role of tumour secretory cytokines and peripheral circulatory cytokines in tumour progression has received increasing attention; however, the role of tumour-related inflammatory cytokines in colorectal cancer (CRC) remains unclear. In this study, the concentrations of various cytokines in the peripheral blood of healthy controls and patients with CRC at different stages were compared. Methods: Peripheral blood samples from 4 healthy participants and 22 colorectal cancer patients were examined. Luminex beads were used to evaluate concentration levels of 40 inflammatory cytokines in peripheral blood samples. Results: In peripheral blood, compared with healthy controls and early stage (I + II) CRC patients, advanced CRC (III + IV) patients had increased concentrations of mononuclear/macrophage chemotactic-related proteins (CCL7, CCL8, CCL15, CCL2, and MIF), M2 polarization-related factors (IL-1ß, IL-4), neutrophil chemotactic and N2 polarization-related cytokines (CXCL2, CXCL5, CXCL6, IL-8), dendritic cells (DCs) chemotactic-related proteins (CCL19, CCL20, and CCL21), Natural killer (NK) cell related cytokines (CXCL9, CXCL10), Th2 cell-related cytokines (CCL1, CCL11, CCL26), CXCL12, IL-2, CCL25, and CCL27, and decreased IFN-γ and CX3CL1 concentrations. The differential upregulation of cytokines in peripheral blood was mainly concentrated in CRC patients with distant metastasis and was related to the size of the primary tumour; however, there was no significant correlation between cytokine levels in peripheral blood and the propensity and mechanism of lymph node metastasis. Discussion: Different types of immune cells may share the same chemokine receptors and can co-localise in response to the same chemokines and exert synergistic pro-tumour or anti-tumour functions in the tumour microenvironment. Chemokines and cytokines affect tumour metastasis and prognosis and may be potential targets for treatment.

Exploring the intestinal ecosystem: from gut microbiota to associations with subtypes of inflammatory bowel disease.

Objective: Significant differences have been discovered between subtypes of Crohn's disease (CD) and ulcerative colitis (UC). The role of gut microbiota in promoting the onset of UC and CD is established, but conclusions regarding subtype-specific analyses remain limited. Methods: This study aims to explore the influence of gut microbiota on subtypes of UC and CD, offering novel insights into the pathogenesis and treatment of UC and CD.Two-sample Mendelian randomization (MR) analysis was employed to examine the causal relationship between subtypes of UC and CD and gut microbiota composition. Gut microbiota data were sourced from the International Consortium MiBioGen, while UC and CD data were obtained from FINNGEN. Eligible single nucleotide polymorphisms (SNPs) were selected as instrumental variables. Multiple analytical approaches such as inverse variance-weighted (IVW), MR-Egger regression, weighted median, weighted mode, and MR-RAPS were utilized. Sensitivity analyses including MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis were conducted for quality control. Subsequently, we employed multivariable IVW, MR-Egger, weighted median, and LASSO regression methods to identify independently significant genera or families and conducted sensitivity analyses. Results: We have determined that Hungatella, Acidaminococcaceae, and 15 other microbial taxa act as protective factors for various CD and UC subtypes, while Terrisporobacter, Anaerostipes, and 23 other microbial taxa are associated with increased risk for different CD and UC subtypes. Furthermore, through multivariable MR analysis, we have identified significant genera or families with independent effects. Conclusion: Our study confirms a causal relationship between dysbiosis of gut microbiota and the occurrence of CD and UC subtypes. Furthermore, it validates etiological distinctions among different subtypes of CD and UC. A novel approach to adjunctive therapy involving distinct UC or CD subtypes may involve the use of probiotics and represents a potential avenue for future treatments.

Dysbiosis of human tumor microbiome and aberrant residence of Actinomyces in tumor-associated fibroblasts in young-onset colorectal cancer.

Colorectal cancer (CRC) is the third most common form of cancer, and the incidence of sporadic young-onset colorectal cancer (yCRC) has been increasing. Microbiota residing in the tumor microenvironment are emerging tumor components. The colonic microbiome differs between patients with CRC and healthy controls; however, few studies have investigated the role of the tumor microbiota in disease diagnosis and tumorigenesis of yCRC. We performed 16S rRNA sequencing analysis to identify the microbiome in CRC and found that tumor microbial diversity decreased in yCRC. Proteobacteria and Firmicutes were the most abundant phyla in all CRC samples, and Actinomyces and Schaalia cardiffensis were the key microbiota in the yCRC group. Correlation analysis revealed that Actinomyces co-occurred with various pro-tumor microbial taxa, including Bacteroidia, Gammaproteobacteria, and Pseudomonas. An independent cohort was used to validate the results. The Actinomyces in CRC was co-localized with cancer-associated fibroblasts and activated the TLR2/NF-κB pathway and reduces CD8+ T lymphocyte infiltration in CRC microenvironment. This study suggests that tumoral microbiota plays an important role in promoting tumorigenesis and therefore has potential as a promising non-invasive tool and intervention target for anti-tumor therapy.

Combination of FOXD1 and Plk2: A novel biomarker for predicting unfavourable prognosis of colorectal cancer.

Colorectal cancer (CRC) is a worldwide disease with worse survival. Our objective is to identify previously unrecognized prognostic factors to better evaluate disease progression. Seven GEO datasets were collected and analysed using R software, followed by KEGG enrichment analysis and TFs network construction. LASSO-COX analysis was performed to select the most useful prognostic features. COX model was used to analyse prognostic factors associated with OS. The survival curve was constructed using Kaplan-Meier analysis. A Nomogram model was also constructed to predict prognosis. A total of 3559 differentially expressed genes (DEGs) and 66 differentially expressed transcription factors were identified. FOXD1 was identified as the most differentially expressed factor of TFs covering the most downstream DEGs and independent risk prognostic factor. Next, FOXD1 expression was detected using immunohistochemical staining in 131 CRC patients' tissue and the association between FOXD1 expression and clinicopathologic features was analysed. High expression of FOXD1 was correlated with TNM stage and pathological differentiation. Multivariate COX regression analyses confirmed that FOXD1 high-expression, TNM stage and tumour differentiation were independent prognostic risk factor of OS and DFS. Patients with high expression of FOXD1 were more likely to have poor overall survival and disease-free survival. The combination of FOXD1 and Plk2 which we have previously reported allowed us to predict the survival of post-surgical CRC patients more accurately, adding to the former prognostic model based on the TNM Stage. The results showed that patients with high expression of both FOXD1 and Plk2 have the worst survival. A combination of FOXD1 and Plk2 can better evaluate patients' survival.

KLF5 inhibition overcomes oxaliplatin resistance in patient-derived colorectal cancer organoids by restoring apoptotic response.

Oxaliplatin resistance is a major challenge in the treatment of colorectal cancer (CRC). Many molecular targeted drugs for refractory CRC have been developed to solve CRC drug resistance, but their effectiveness and roles in the progression of CRC and oxaliplatin resistance remain unclear. Here, we successfully constructed CRC PDOs and selected the Kruppel-like factor 5 (KLF5) inhibitor ML264 as the research object based on the results of the in vitro drug screening assay. ML264 significantly restored oxaliplatin sensitivity in CRC PDOs by restoring the apoptotic response, and this effect was achieved by inhibiting the KLF5/Bcl-2/caspase3 signaling pathway. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays verified that KLF5 promoted the transcription of Bcl-2 in CRC cells. KLF5 inhibition also overcame oxaliplatin resistance in xenograft tumors. Taken together, our study demonstrated that ML264 can restore oxaliplatin sensitivity in CRC PDOs by restoring the apoptotic response. KLF5 may be a potential therapeutic target for oxaliplatin-resistant CRC. PDOs have a strong potential for evaluating inhibitors and drug combination therapy in a preclinical environment.

CCL7 and TGF-ß secreted by MSCs play opposite roles in regulating CRC metastasis in a KLF5/CXCL5-dependent manner.

CXCL5 is overexpressed in colorectal cancer (CRC) and promotes distant metastasis and angiogenesis of tumors; however, the underlying mechanism that mediates CXCL5 overexpression in CRC remains unclear. Here, we successfully extracted and identified primary mesenchymal stromal cells (MSCs) and verified the promoting effects of tumor-associated MSCs on CRC proliferation and metastasis in vivo and in vitro. We found that MSCs not only promoted the expression of CXCL5 by secreting CCL7 but also secreted TGF-ß to inhibit this process. After secretion, CCL7/CCR1 activated downstream CBP/P300 to acetylate KLF5 to promote CXCL5 transcription, while TGF-ß reversed the effect of KLF5 on transcription activation by regulating SMAD4. Taken together, our results indicate that MSCs in the tumor microenvironment promoted the progression and metastasis of CRC and regulated the expression of CXCL5 in CRC cells by secreting CCL7 and TGF-ß. KLF5 is the key site of these processes and plays a dual role in CXCL5 regulation. MSCs and their secreted factors may serve as potential therapeutic targets in the tumor environment.

Platelet infiltration predicts survival in postsurgical colorectal cancer patients.

Platelets promote tumor growth and metastasis in several tumor types. Recent research has found platelets can extravasate and infiltrate into the tumor stroma and interact with the tumor microenvironment. The prognostic role of platelet infiltration in colorectal cancer (CRC) remains controversial. A pan-cancer survival analysis was performed to find the potential prognostic value of platelet infiltration in patients with cancer. A survival analysis and a nomogram prognostic model were established to further confirm the results with data from our center. The correlations between patient outcomes and tumor-infiltrating platelets (TIPs) were identified by immunohistochemical staining for CD42b. The prognostic accuracy and discriminative ability of the nomogram were determined by the concordance index (C-index) and a calibration curve. The pan-cancer survival analysis showed platelet infiltration can lead to a poor prognosis in patients with several types of cancers, including CRC. Platelet infiltration was associated with overall survival (OS) and disease-free survival (DFS) in both primary and validation cohorts. The C-index values of the nomogram for predicting OS and DFS were 0.774 and 0.769, respectively, which were higher than that of the TNM staging system alone. Our study found platelet infiltration has a potential prognostic value regarding postsurgical survival in CRC patients. The proposed nomogram resulted in a more accurate prognostic prediction for postsurgical CRC patients.

Continuous cardiovascular hemodynamics monitoring with pressure recording analytical method in patients under spinal anesthesia for elective cesarean section: a pilot study.

BACKGROUND: Pressure recording analytical method (PRAM) of MOSTCARE is a minimally invasive system based on mathematical analysis of arterial pressure profile changes and allows continuous recording of hemodynamic measurements. Herein, we aimed to use the MostCare system to investigate the hemodynamics of patients receiving spinal anesthesia during elective cesarean section. METHODS: In this observational study, we recruited 17 patients scheduled for elective cesarean section. For each patient, we acquired continuous recordings of hemodynamic parameters at 14 key timepoints: surgical admission (two baseline parameters), immediately after the administration of spinal anesthesia, six subsequent time points (2, 4, 6, 8, 10, and 12 min after anesthesia), during peritoneum and uterine incision, during delivery, following the administration of oxytocin, and after surgery had been completed. Statistical analysis was carried out by repeated measures analysis of variance (ANOVA). RESULTS: During a twelve min period after spinal anesthesia, we observed significant reductions in mean arterial pressure (MAP), dicrotic pressure (Pdic), cardiac index (CI), stroke volume index (SVI), dP/dtmax, and cardiac cycle efficiency (CCE) (P<0.05 for all). However, systemic vascular resistance index (SVRI) was reversely correlated to CI and increased significantly after spinal anesthesia (P<0.05). These hemodynamic parameters return to near basal values after peritoneum incision. Furthermore, there were significant fluctuations in MAP, Pdic and CI after oxytocin administration (P<0.05). CONCLUSIONS: PRAM of MostCare system revealed significant changes in key hemodynamic parameters undergoing cesarean section with spinal anesthesia. It enables clinicians gain a much better understanding of hemodynamics of parturients and optimize clinical management strategies. TRIAL REGISTRATION: This study was registered at http://www.chictr.org.cn on 16, July, 2019. No. ChiCTR1900024566.

Retrospective research of neoadjuvant therapy on tumor-downstaging, post-operative complications, and prognosis in locally advanced rectal cancer.

BACKGROUND: Neoadjuvant therapy (NAT) is becoming increasingly important in locally advanced rectal cancer. Hence, such research has become a problem. AIM: To evaluate the downstaging effect of NAT, its impact on postoperative complications and its prognosis with different medical regimens. METHODS: Seventy-seven cases from Shanghai Ruijin Hospital affiliated with Shanghai Jiaotong University School of Medicine were retrospectively collected and divided into the neoadjuvant radiochemotherapy (NRCT) group and the neoadjuvant chemotherapy (NCT) group. The differences between the two groups in tumor regression, postoperative complications, rectal function, disease-free survival, and overall survival were compared using the χ 2 test and Kaplan-Meier analysis. RESULTS: Baseline data showed no statistical differences between the two groups, whereas the NRCT group had a higher rate of T4 (30/55 vs 5/22, P < 0.05) than the NCT groups. Twelve cases were evaluated as complete responders, and 15 cases were evaluated as tumor regression grade 0. Except for the reduction rate of T stage (NRCT 37/55 vs NCT 9/22, P < 0.05), there was no difference in effectiveness between the two groups. Preoperative radiation was not a risk factor for poor reaction or anastomotic leakage. No significant difference in postoperative complications and disease-free survival between the two groups was observed, although the NRCT group might have better long-term overall survival. CONCLUSION: NAT can cause tumor downstaging preoperatively or even complete remission of the primary tumor. Radiochemotherapy could lead to better T downstaging and promising overall survival without more complications.

High versus low ligation of the inferior mesenteric artery during laparoscopic rectal cancer surgery: A prospective study of surgical and oncological outcomes.

BACKGROUND AND OBJECTIVES: There is controversy regarding whether the inferior mesenteric artery (IMA) should be ligated at its origin from the aorta (high ligation, HL) or below the branch of the left colic artery (low ligation, LL) during surgery for rectal cancer. METHODS: This prospective study randomized 95 patients with histologically proven rectal cancer (clinical stages I-III based on the 8th American Joint Committee on Cancer guidelines) to undergo HL (n = 47) or LL with lymph node dissection at the root of the IMA (n = 48). RESULTS: Only two intraoperative adverse events were observed (two HL patients experienced anastomotic ischemia and underwent extended bowel excision and splenic flexure mobilization). The LL group had a significantly shorter time to first flatus (p < .0001). No significant differences were observed in operative time (p = .14), intraoperative blood loss (p = .21), distance from the upper margin (p = .77), distance from the lower margin (p = .35), harvested lymph nodes (p = .33), or anastomotic leakage (p = .44), 2-year overall survival (p = .97), or 2-year disease-free survival (p = .42). CONCLUSION: During laparoscopic low anterior resection, a combination of LL at the IMA and vascular root lymph node dissection may help protect the blood supply of the anastomosis, reduce postoperative complications, and enhance recovery, without compromising radical excision.

A small dose of dezocine suppresses remifentanil-induced cough in general anesthesia induction: a prospective, randomized, controlled study.

BACKGROUND: The aim of this prospective randomized controlled study was to evaluate whether pretreatment with a small dose of dezocine could prevent remifentanil-induced cough in general anesthesia induction. TRIAL DESIGN: a prospective, randomized, controlled study. METHODS: A total of 210 patients receiving elective operative hysteroscopy from December 2018 to April 2019 were enrolled in the present study. They were randomly equally separated into dezocine group (n = 105) and control group (n = 105). Patients were intravenously pre-administrated with dezocine 0.03 mg/kg (diluted to 5 mL) or the same volume of normal saline 1 min prior to remifentanil infusion. One minute later, intravenous injection of propofol 1.5 mg/kg and cisatracurium 0.1 mg/kg were given to all patients for induction of general anesthesia. The counts of coughs occurred during the anesthesia induction period were recorded and the severity of cough was scaled. RESULTS: There were 7 cases of mild cough in dezocine group and 18 cases of mild cough, 12 cases of moderate cough and 4 cases of severe cough in control group. The incidence rate of cough was significantly lower and the severity of cough was obviously relieved in dezocine group compared to control group (6.67% vs. 32.38%, P <  0.001). The two groups were not significantly different in heart rate and mean arterial pressure before the induction, before and after the intubation, and in operating time and postoperative visual analog scale pain scores. CONCLUSION: This study recommends the efficacy and safety of a pretreatment with a small dose of dezocine in reducing remifentanil-induced cough during general anesthesia. TRIAL REGISTRATION: ChiCTR2000032035 . Date of registration: Retrospectively registered on 2020/04/18.

Propofol Suppressed Hypoxia/Reoxygenation-Induced Apoptosis in HBVSMC by Regulation of the Expression of Bcl-2, Bax, Caspase3, Kir6.1, and p-JNK.

Recent studies have found that propofol may protect brain from cerebral ischemic-reperfusion injury. However, the underlying mechanism remains unclear. The effects of propofol were evaluated in HBVSMC after hypoxia/reoxygenation (H/R). Cell viability and levels of SOD, LDH, and MDA were measured. Apoptosis was detected by flow cytometry. The levels of Bax, Bcl-2, Caspase3, Sur2b, Kir6.1, JNK, p-JNK, mTOR, and p-mTOR proteins were measured by western blotting. H/R decreased cell viability and SOD activity and increased LDH leakage and MDA content in HBVSMC, all of which were significantly reversed by propofol. Propofol suppressed the levels of H/R-induced apoptosis. The expression of Bcl-2 and p-mTOR was significantly downregulated and the expression levels of Bax, Caspase3, Kir6.1, and p-JNK were upregulated following H/R injury. The ratio of p-JNK/JNK was increased; however, that of p-mTOR/mTOR decreased correspondingly. The effects on the expression of these proteins were reversed by propofol treatment. SP600125 enhanced and Everolimus attenuated the effect of propofol. These findings suggested that the protective effect of propofol against H/R injury in the HBVSMC was through the inhibition of apoptosis by inducing the expression of Bcl-2 and p-mTOR as well as inhibiting the expression levels of Bax, Caspase3, Kir6.1, and p-JNK.

Pleth variability index-directed fluid management in abdominal surgery under combined general and epidural anesthesia.

Pleth variability index (PVI), a noninvasive dynamic indicator of fluid responsiveness has been demonstrated to be useful in the management of the patients with goal directed fluid therapy under general anesthesia, but whether PVI can be used to optimize fluid management under combined general and epidural anesthesia (GEN-EPI) remains to be elucidated. The aim of our study was to explore the impact of PVI as a goal-directed fluid therapy parameter on the tissue perfusion for patients with GEN-EPI. Thirty ASA I-II patients scheduled for major abdominal surgeries under GEN-EPI were randomized into PVI-directed fluid management group (PVI group) and non PVI-directed fluid management group (control group). 2 mL/kg/h crystalloid fluid infusion was maintained in PVI group, once PVI>13%, a 250 mL colloid or crystalloid was rapidly infused. 4-8 mL/kg/h crystalloid fluid infusion was maintained in control group, and quick fluid infusion was initiated if mean arterial blood pressure (BP)<65 mmHg. Small doses of norepinephrine were given to keep mean arterial BP above 65 mmHg as needed in both groups. Perioperative lactate levels, hemodynamic changes were recorded individually. The total amount of intraoperative fluids, the amount of crystalloid fluid and the first hour blood lactate levels during surgery were significantly lower in PVI than control group, P<0.05. PVI-based goal-directed fluid management can reduce the intraoperative fluid amount and blood lactate levels in patients under GEN-EPI, especially the crystalloid. Furthermore, the first hour following GEN-EPI might be the critical period for anesthesiologist to optimize the fluid management.

The pleth variability index as an indicator of the central extracellular fluid volume in mechanically ventilated patients after anesthesia induction: comparison with initial distribution volume of glucose.

BACKGROUND: The pleth variability index (PVI) has been demonstrated to be a useful, noninvasive indicator of continuous fluid responsiveness. Whether PVI can be used to assess the changes of intravascular volume status remains to be elucidated. MATERIAL AND METHODS: Using correlation analysis and receiver operating characteristic (ROC) curves, we sought a correlation between PVI and the initial distribution volume of glucose (IDVG), evaluating PVI as an indicator of the central extracellular fluid volume after anesthesia induction in patients undergoing elective abdominal surgery. RESULTS: Strong negative correlations existed between IDVG and PVI (r=-0.72), IDVG, and pulse pressure variation (PPV) (r=-0.73), and between IDVG and systolic pressure variation (SPV) (r=-0.53), P<0.01. Strong positive correlations existed between PPV and PVI (r=0.66), PVI and SPV (r=0.49), and between PPV and SPV (r=0.59), P<0.01. The areas under the ROC curve of IDVG, PVI, and SPV were significantly different from the area under a reference line. The optimal cutoff values (followed by sensitivity and specificity in parentheses) comparable to PPV over 11% as the threshold of hypovolemia were IDVG 94.5 mL/kg (75%, 100%), PVI 13% (91.7%, 77.8%), and SPV 7% (41.7%, 100%). CONCLUSIONS: Our results show that strong correlations exist among IDVG, PVI, PPV, and SPV in the evaluation of volemia. PVI can serve as a useful, noninvasive indicator of continuous central extracellular fluid volume for those patients not requiring invasive hemodynamic monitoring, but needs attention to changes in intravascular volume status for optimal fluid management.