Prevention of dexmedetomidine on postoperative delirium and early postoperative cognitive dysfunction in elderly patients undergoing hepatic lobectomy. / å³ç¾Žæ‰˜å’ªå®šå¯¹è€å¹´æ‚£è€ è‚å¶åˆ‡é™¤æœ¯åŽè°µå¦„å’Œæ—©æœŸæœ¯åŽè®¤çŸ¥åŠŸèƒ½éšœç¢çš„é¢„é˜²æ•ˆæžœ.

OBJECTIVES: Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are common operative neurocognitive disorders, which places a heavy burden on patients, families and society. Therefore, it is very important to search for preventive drugs. Previous studies have demonstrated that perioperative use of dexmedetomidine resulted in a decrease the incidence of POD and POCD. But the specific effect of dexmedetomidine on elderly patients undergoing hepatic lobectomy and its potential mechanism are not clear. This study aims to evaluate the efficacy of intraoperative use of dexmedetomidine on preventing POD and POCD in elderly patients undergoing hepatic lobectomy and the influence on the balance between proinflammation and anti-inflammation. METHODS: This trial was designed as a single-center, prospective, randomized, controlled study. One hundred and twenty hospitalized patients from January 2019 to December 2020, aged 60-80 years old with American Society of Anesthesiologists (ASA) II-III and scheduled for hepatic lobectomy, were randomly allocated into 3 groups (n=40) using a random number table: A C group, a Dex1 group, and a Dex2 group. After anesthesia induction, saline in the C group, dexmedetomidine [0.3 µg/(kg·h)] in the Dex1 group, and dexmedetomidine [0.6 µg/(kg·h)] in the Dex2 group were infused until the end of operation. The incidences of hypotension and bradycardia were compared among the 3 groups. Confusion Assessment Method (CAM) for assessing POD and Mini Mental State Examination (MMSE) for evaluating POCD were recorded and venous blood samples were obtained for the determination of neuron specific enolase (NSE), TNF-α, IL-1ß, and IL-10 at the different time below: the time before anesthesia (T0), and the first day (T1), the third day (T2), the fifth day (T3), and the seventh day (T4) after operation. RESULTS: Compared with the C group, the incidences of bradycardia in the Dex1 group or the Dex2 group increased (both P<0.05) and there was no difference in hypotension in the Dex1 group or the Dex2 group (both P>0.05). The incidences of POD in the C group, the Dex1 group, and the Dex2 group were 22.5%, 5.0%, and 7.5%, respectively. The incidences of POD in the Dex1 group or the Dex2 group declined significantly as compared to the C group (both P<0.05). However, there is no difference in the incidence of POD between the Dex1 group and the Dex2 group (P>0.05). The incidences of POCD in the C group, the Dex1 group, and the Dex2 group were 30.0%, 12.5%, and 10.0%, respectively. The incidences of POCD in the Dex1 group and the Dex2 group declined significantly as compared to the C group (both P<0.05). And no obvious difference was seen in the incidence of POCD in the Dex1 group and the Dex2 group (P>0.05). Compared with the C group, the level of TNF-α and IL-1ß decreased and the level of IL-10 increased at each time points (from T1 to T4) in the Dex1 group and the Dex2 group (all P<0.05). Compared with the Dex1 group, the level of IL-1ß at T2 and IL-10 from T1 to T3 elevated in the Dex2 group (all P<0.05). Compared with the T0, the concentrations of NSE in C group at each time points (from T1 to T4) and in the Dex1 group and the Dex2 group from T1 to T3 increased (all P<0.05). Compared with the C group, the level of NSE decreased from T1 to T4 in the Dex1 group and the Dex2 group (all P<0.05). CONCLUSIONS: Intraoperative dexmedetomidine infusion can reduce the incidence of POCD and POD in elderly patients undergoing hepatic lobectomy, and the protective mechanism appears to involve the down-regulation of TNF-α and IL-1ß and upregulation of IL-10 expression, which lead to rebalance between proinflammation and anti-inflammation.

The Effect of a Small Priming Dose of Sufentanil on Sufentanil-Induced Cough.

PURPOSE: The aim of this study was to investigate the effect of a small priming dose of sufentanil on sufentanil-induced cough during induction of anesthesia. DESIGN: Randomized controlled trial. METHODS: Adult patients (N = 220) aged 18 to 65 years undergoing general anesthesia were randomized into two groups (n = 110), a total dose of sufentanil 0.4 mcg/kg was used during induction of anesthesia. Group P (intervention) received a bolus of 5 mcg of sufentanil 1 minute before a bolus of the remaining larger dose of sufentanil, whereas group C (comparison) received an equal volume of normal saline 1 minute before a bolus of the total dose of sufentanil. The incidence and severity of cough were noted for 1 minute after each injection of sufentanil or normal saline. FINDINGS: The incidence of cough in group P was significantly lower than group C (6.4% vs 21.8%, P < .001). The severity of cough in group P was significantly decreased compared with group C (P < .001). In group P, three patients (2.7%, P = .247) coughed after the priming sufentanil injection. CONCLUSIONS: A priming dose of 5 mcg of sufentanil 1 minute before a larger dose of sufentanil injection could effectively alleviate sufentanil-induced cough, the small priming dose of sufentanil could also elicit cough with a low incidence.

Effect of Tramadol Pretreatment on Sufentanil-Induced Cough.

PURPOSE: To investigate the effect of tramadol pretreatment on the incidence and severity of sufentanil-induced cough. DESIGN: Randomized controlled trial. METHODS: Adults of both genders (N = 304; 18 to 65 years old, American Society of Anesthesiologists physical status I to II), scheduled for elective surgery, were randomized into two groups (n = 152): intravenous administration of tramadol 1 mg/kg (group T) or normal saline (group C). Then sufentanil bolus 0.3 mcg/kg was administered intravenously in 5 seconds. The incidence and severity of cough were observed for 1 minute. Mean arterial pressure, heart rate, nausea, vomiting, and truncal rigidity during induction were also recorded. FINDINGS: Patient characteristics were similar between the two groups. The incidence of cough was significantly lower in group T when compared with group C (7.9% vs 18.4%, P < .05); there were nine patients coughing severely in group C, whereas no severe cough occurred in group T (P < .05). The mean arterial pressure, heart rate, and incidences of other side effects were comparable between the two groups. CONCLUSIONS: Pretreatment of intravenous tramadol 1 mg/kg could be a clinically effective intervention for attenuating sufentanil-induced cough.

[Aucubin alleviates lipopolysaccharide-induced acute lung injury in mice].

OBJECTIVE: To investigate the effect of prophylactic aucubin (AU) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. 
 Methods: Male BABL/c mice were randomly divided into a control group, an ALI group, and an AU treatment group, 16 mice in each group. ALI mice were injected with LPS (5 mg/kg, intratracheal injection), and AU (10 mg/kg) was injected intraperitoneally 30 min ahead. After LPS injection for 6 hours mice were sacrificed, the morphological changes of lung tissues were detected by HE staining and the lung injury score was obtained. The mRNA expression of tumor necrosis factor-α (TNF-α) and interleukin 10 (IL-10) in lung tissue was detected by real-time PCR. The total protein and lactate dehydrogenase (LDH) activity, the cell count, and the protein content of TNF-α and IL-10 in the mouse bronchoalveolar lavage fluid (BALF) were detected.
 Results: Compared with ALI mice, the pathological damage score of lung tissue was significantly reduced in the AU group, the total number of BALF cells, neutrophils, and macrophages were significantly decreased, LDH activity and the total protein content were also significantly decreased (all P<0.01). In addition, AU can reduce the mRNA and protein expression of TNF-α in lung of ALI mice, and increase the mRNA and protein expression of IL-10 (all P<0.01).
 Conclusion: AU can reduce LPS-induced ALI in mice.

Analysis and experimental validation of IL-17 pathway and key genes as central roles associated with inflammation in hepatic ischemia-reperfusion injury.

Hepatic ischemia-reperfusion injury (HIRI) elicits an immune-inflammatory response that may result in hepatocyte necrosis and apoptosis, ultimately culminating in postoperative hepatic dysfunction and hepatic failure. The precise mechanisms governing the pathophysiology of HIRI remain incompletely understood, necessitating further investigation into key molecules and pathways implicated in disease progression to guide drug discovery and potential therapeutic interventions. Gene microarray data was downloaded from the GEO expression profile database. Integrated bioinformatic analyses were performed to identify HIRI signature genes, which were subsequently validated for expression levels and diagnostic efficacy. Finally, the gene expression was verified in an experimental HIRI model and the effect of anti-IL17A antibody intervention in three time points (including pre-ischemic, post-ischemic, and at 1 h of reperfusion) on HIRI and the expression of these genes was investigated. Bioinformatic analyses of the screened characterized genes revealed that inflammation, immune response, and cell death modulation were significantly associated with HIRI pathophysiology. CCL2, BTG2, GADD45A, FOS, CXCL10, TNFRSF12A, and IL-17 pathway were identified as key components involved in the HIRI. Serum and liver IL-17A expression were significantly upregulated during the initial phase of HIRI. Pretreatment with anti-IL-17A antibody effectively alleviated the damage of liver tissue, suppressed inflammatory factors, and serum transaminase levels, and downregulated the mRNA expression of CCL2, GADD45A, FOS, CXCL10, and TNFRSF12A. Injection of anti-IL17A antibody after ischemia and at 1 h of reperfusion failed to demonstrate anti-inflammatory and attenuating HIRI benefits relative to earlier intervention. Our study reveals that the IL-17 pathway and related genes may be involved in the proinflammatory mechanism of HIRI, which may provide a new perspective and theoretical basis for the prevention and treatment of HIRI.

Association of peripheral B cells and delirium: combined single-cell sequencing and Mendelian randomization analysis.

Background: Delirium seriously affects the prognosis of patients and greatly reduces the ability to work and live. Peripheral inflammatory events may contribute to the development of delirium, the mechanism of which is still unclear. There is a lack of effective diagnostic and treatments for delirium in clinical practice. The study aims to investigate alterations in peripheral immune cell subsets under inflammatory stress and to explore causal associations with delirium. Methods: Single-cell transcriptional sequencing data of human peripheral blood mononuclear cells (PBMC) before and after lipopolysaccharide (LPS) intervention were processed by the Seurat package in R software. PBMC subsets and cellular markers were defined after downscaling and clustering by the Harmony algorithm to identify characteristic subsets in the context of inflammatory stress. Subsequently, a two-sample Mendelian randomization (MR) study was used to explore the causal associations of these inflammation-related PBMC subsets and their molecular phenotypes with delirium. Based on publicly available genetic data, the study incorporated 70 PBMC-associated immune traits, including 8 types of circulating immune cells, 33 B cell subsets and molecular phenotypes, 13 T cell subsets, and 16 B cell-associated cytokines. The results were also validated for robustness, heterogeneity, and horizontal pleiotropy. Results: Under LPS-induced inflammatory stress, B cells, T cells, monocytes, and dendritic cells in human PBMC showed significant activation and quantitative changes. Of these, only lymphocyte and B cell counts were causally associated with delirium risk. This risk link is also seen in the TNF pathway. Further studies of B cells and their subsets revealed that this association may be related to unswitched memory B cells and CD27 expressed on memory B cells. Annotation of the screened SNPs revealed significant polymorphisms in CD27 and CD40 annotated by rs25680 and rs9883798, respectively. The functions of the key annotated genes may be related to the regulation of immune responses, cell differentiation, proliferation, and intercellular interactions. Conclusion: The present study revealed the potential possibility that B cell, memory B cell subset, and TNF-related molecules may be involved in the development of delirium due to peripheral inflammation, which can provide clues for further investigation of delirium prevention and treatment strategies.

Clinical practice guidelines for prevention and treatment of postoperative gastrointestinal disorder with Integrated Traditional Chinese and Western Medicine (2023).

Postoperative gastrointestinal disorder (POGD) was a common complication after surgery under anesthesia. Strategies in combination with Traditional Chinese Medicine and Western medicine showed some distinct effects but standardized clinical practice guidelines were not available. Thus, a multidisciplinary expert team from various professional bodies including the Perioperative and Anesthesia Professional Committees of the Chinese Association of Integrative Medicine (CAIM), jointly with Gansu Province Clinical Research Center of Integrative Anesthesiology/Anesthesia and Pain Medical Center of Gansu Provincial Hospital of Traditional Chinese Medicine and WHO Collaborating Center for Guideline Implementation and Knowledge Translation/Chinese Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Center/Gansu Provincial Center for Medical Guideline Industry Technology/Evidence-based Medicine Center of Lanzhou University, was established to develop evidence-based guidelines. Clinical questions (7 background and 12 clinical questions) were identified through literature reviews and expert consensus meetings. Based on systematic reviews/meta-analyses, evidence quality was analyzed and the advantages and disadvantages of interventional measures were weighed with input from patients' preferences. Finally, 20 recommendations were developed through the Delphi-based consensus meetings. These recommendations included disease definitions, etiologies, pathogenesis, syndrome differentiation, diagnosis, and perioperative prevention and treatment.

Peripheral inflammation and neurocognitive impairment: correlations, underlying mechanisms, and therapeutic implications.

Cognitive impairments, such as learning and memory deficits, may occur in susceptible populations including the elderly and patients who are chronically ill or have experienced stressful events, including surgery, infection, and trauma. Accumulating lines of evidence suggested that peripheral inflammation featured by the recruitment of peripheral immune cells and the release of pro-inflammatory cytokines may be activated during aging and these conditions, participating in peripheral immune system-brain communication. Lots of progress has been achieved in deciphering the core bridging mechanism connecting peripheral inflammation and cognitive impairments, which may be helpful in developing early diagnosis, prognosis evaluation, and prevention methods based on peripheral blood circulation system sampling and intervention. In this review, we summarized the evolving evidence on the prevalence of peripheral inflammation-associated neurocognitive impairments and discussed the research advances in the underlying mechanisms. We also highlighted the prevention and treatment strategies against peripheral inflammation-associated cognitive dysfunction.

ASPM May be Related to the Malignant Progression of Hepatitis B and is Associated With a Poor Prognosis of Hepatocellular Carcinoma.

Background: Hepatitis B virus (HBV) is a causative agent of hepatocellular carcinoma (HCC). Until now, the mechanism behind the progress of hepatitis B fibrosis to HCC remains largely unknown. This study aims to examine the candidate biomarkers and pathways involved in HBV-associated HCC. Methods: Gene expression profiles were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the GEO2R tool after which functional enrichment analysis, protein-protein interaction (PPI) analysis, genetic alteration analysis, prognostic analysis, immune infiltration analysis, co-expression genes prediction, and miRNA-gene network construction, and pathway correlation analysis were performed. Results: 22 hub genes were identified, which were all highly expressed in HCC, and overexpression of these genes was all associated with significantly worse survival in HCC patients. More significantly, ASPM also showed increased expression levels in non-tumor tissues with advanced liver fibrosis. With the progression of liver fibrosis and the closer tumor center of HCC, the higher expression of ASPM was identified. ASPM was considered to be the most promising biomarker because it also showed the highest genetic alteration frequency among the hub genes and the expression level of ASPM in HBV (+) HCC tissues was significantly higher than that in HBV (-) HCC tissues. Also, the infiltration levels of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells were all positively correlated with the expression of ASPM. Conclusion: These findings may help in the development of strategies and candidate drugs for the treatment of HBV-related HCC and improve the effectiveness of personalized treatment in the future. ASPM was upregulated in both hepatitis B cirrhosis and HCC and could be a potential predicting biomarker.

Changes of inflammatory factors in patients after resection of lung adenocarcinoma with propofol and etomidate.

OBJECTIVE: This research was designed to investigate the changes of inflammatory factors in patients after resection of lung adenocarcinoma with propofol versus etomidate. METHODS: A total of 104 patients who underwent resection of lung adenocarcinoma in our hospital were divided into a propofol group (group A, n=50) and an etomidate group (group B, n=54). The levels of CRP and IL-6 at different time points and the changes of blood gas indexes at 10 min before and after operation were observed in both groups. Their pain score and quality of life score were compared. Besides, we observed the wake-up time, tracheal extubation time and the incidence of adverse reactions. RESULTS: The anesthesia recovery and tracheal extubation time in group B were shorter than those in group A (P<0.05). After 10-minutes of spontaneous breathing, PaO2 and SaO2 in group B were higher than those in group A (P<0.05), and PaCO2 was lower (P<0.05); compared with group A. The incidence of adverse reactions and the levels of inflammatory factors in group B were lower than those in group A after operation (both P<0.05). The quality of life of patients in group B after operation was better than that in group A (P<0.05). There was no marked difference in VAS scores between groups. CONCLUSION: Etomidate has better anesthetic effect than propofol in lung adenocarcinoma resection, leading to better stabilization of the vital signs of patients and it also has higher safety.

Screening druggable targets and predicting therapeutic drugs for COVID-19 via integrated bioinformatics analysis.

BACKGROUND: Since the outbreak of coronavirus disease 2019 (COVID-19) in China, numerous research institutions have invested in the development of anti-COVID-19 vaccines and screening for efficacious drugs to manage the virus. OBJECTIVE: To explore the potential targets and therapeutic drugs for the prevention and treatment of COVID-19 through data mining and bioinformatics. METHODS: We integrated and profoundly analyzed 10 drugs previously assessed to have promising therapeutic potential in COVID-19 management, and have been recommended for clinical trials. To explore the mechanisms by which these drugs may be involved in the treatment of COVID-19, gene-drug interactions were identified using the DGIdb database after which functional enrichment analysis, protein-protein interaction (PPI) network, and miRNA-gene network construction were performed. We adopted the DGIdb database to explore the candidate drugs for COVID-19. RESULTS: A total of 43 genes associated with the 10 potential COVID-19 drugs were identified. Function enrichment analysis revealed that these genes were mainly enriched in response to other invasions, toll-like receptor pathways, and they play positive roles in the production of cytokines such as IL-6, IL-8, and INF-ß. TNF, TLR3, TLR7, TLR9, and CXCL10 were identified as crucial genes in COVID-19. Through the DGIdb database, we predicted 87 molecules as promising druggable molecules for managing COVID-19. CONCLUSIONS: Findings from this work may provide new insights into COVID-19 mechanisms and treatments. Further, the already identified candidate drugs may improve the efficiency of pharmaceutical treatment in this rapidly evolving global situation.

The effect of intravenous lidocaine on hemodynamic response to endotracheal intubation during sufentanil-based induction of anaesthesia.

INTRODUCTION: Endotracheal intubation (ETI) can cause a cardiovascular response. The aim of the present study was to investigate the effect of intravenous lidocaine on the hemodynamic response to ETI during sufentanil-based induction of anaesthesia. MATERIAL AND METHODS: Ninety patients aged 18-65 years were recruited, induction of anaesthesia was initiated by sufentanil, midazolam, cisatracurium, and propofol, the patients were randomized to three groups: Group L1 received 1 mg/kg-1 of lidocaine, Group L1.5 received 1.5 mg kg-1 of lidocaine, Group S received an equal volume of normal saline (NS). Lidocaine or NS was administered in a bolus 2 min before ETI. Systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), and heart rate (HR) were recorded at four time points: before anaesthetic induction, 1 min after lidocaine administration, immediately after ETI, 5 min after ETI. The incidences of hypotension, hypertension, bradycardia, and tachycardia were also recorded. RESULTS: The SAP, DAP, MAP, and HR at baseline were not significantly different among the three groups (P = 0.620, P = 0.575, P = 0.433, P = 0.537, respectively). Immediately after ETI, the SAP in Group L1 was significantly lower than Group S (P = 0.024), while the DAP, MAP, and HR were comparable among the three groups at the same time points (P > 0.05). There were no significant differences in the incidences of hypotension, hypertension, bradycardia and tachycardia among the three groups (P > 0.200). CONCLUSIONS: Intravenous lidocaine could attenuate the increase of blood pressure but not HR after ETI during sufentanil-based induction of anaesthesia without increased incidence of side-effects.

[Electroacupuncture at "Ganshu" (BL18) and "Yanglingquan" (GB34) alleviates hepatic ischemia-reperfusion injury by inhibiting translocation and release of high mobility group protein 1 in rats].

OBJECTIVE: To explore the protective effect of electroacupuncture (EA) on hepatic ischemia-reperfusion injury (HIRI) and the expression of high mobility group protein 1 (HMGB1) in liver tissues in rats. METHODS: A total of 40 male SD rats were randomly divided into 4 groups, namely sham control, HIRI model, "Ganshu"(BL18) -"Yanglingquan"(GB34) and non-acupoint group, with 10 rats in each group. The HIRI model was induced by blocking the arteries, veins and bile ducts supplying the middle and left lobes of the liver for 1 h, and reperfusion for 4 h to induce an area of about 70% HIRI. EA was applied to bila-teral BL18 and GB34, or non-acupoints about 6-8 mm to the bilateral BL18 for 30 min before modeling. Serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels were measured by using an automatic biochemical analyzer. Serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and HMGB1 levels were assayed by ELISA. Hematoxylin - eosin (H.E.) staining was used to observe histopathological changes of the liver tissue by using tissue injury scaling (0-3 scores). The expression of HMGB1 protein in liver tissues was detected by immunohistochemical staining, Western blot and PCR, separately. RESULTS: Following modeling and compared with the sham group, the levels of serum ALT, AST, TNF-α, IL-6, and HMGB1 contents, the number of HMGB1 immunoreaction (IR)-positive cells, and HMGB1 protein and mRNA were significantly increased (P＜0.01). After the treatment, the contents of serum ALT, AST, TNF-α, IL-6, and HMGB1, liver HMGB1 IR-positive cells, protein and mRNA were considerably down-regulated in the BL18-GB34 group (P<0.05), rather than in the non-acupoint group (P>0.05) in contrast to the model group. H.E. stain showed a higher liver injury score in the model group than in the sham group (P<0.01), and a lower liver injury score in the BL18-GB34 group (not the non-acupoint group) relevant to the model group (P<0.05). CONCLUSION: EA of BL18 and GB34 points has a protective effect on ischemic liver injury in rats with HIRI, which may be associated with its functions in inhibiting the migration and release of HMGB1 from the nucleus to the cytoplasm and in down-regulating the expression of inflammatory factors.

Clinicopathological findings and imaging features of intraductal papillary neoplasms in bile ducts.

BACKGROUND: Intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) is considered an uncommon tumor, and there is limited understanding of IPMN-B. This study aimed to investigate the prognosis and influential factors of the IPMN-B from 58 cases. METHODS: The clinical data of 58 patients with pathologically confirmed IPMN-B admitted to our hospital from January 1, 2012 to August 2017 were collected and analyzed. The patients were followed up by outpatient or telephone until January 1, 2019. SPSS 19.0 software was applied for data analysis. Survival analysis was performed using Kaplan-Meier method and parallel Log-rank test. Prognostic factors were analyzed by univariate analysis and multiple Cox regression model. RESULTS: Among of all the patients, 26 cases were benign tumors and 32 cases were malignant tumors. The preoperative tumor markers CA242 and CEA of malignant IPNM-B patients were significantly higher than those in benign tumors (P < 0.05). Survival analysis showed that patients with malignant tumors had a worse prognosis. The median survival time of malignant IPMN-B patients was 40.6 ±  3.0 months, yet median survival time of benign IPMN-B patients was not reached (P = 0.19). The one-year survival rate and three-year survival rate of benign IPMN-B were 84% and 74% respectively. The one-year survival rate and three-year survival rate of malignant IPMN-B were 88% and 64% respectively. Univariate analysis showed that combined lymph node metastasis, surgical method, and differentiation degree could affect patients' prognosis (P < 0.05). Multivariate analysis showed differentiation degree was an independent risk factor affecting prognosis (OR = 0.06, 95% confidence interval: 0.007∼0.486, P < 0.05). CONCLUSION: The levels of CEA and CA242 were helpful to identify benign and malignant of IPNM-B. Moreover, radical surgical resection could prolong patients' survival. Finally, differentiation degree was an independent risk factor affecting malignant IPNM-B prognosis.

Effects of propofol combined with remifentanil anesthesia on the NO, endothelin and inflammatory cytokines in the plasma of patients with liver cirrhosis during the perioperative period.

The effects of propofol combined with remifentanil on the nitric oxide (NO), endothelin (ET-1) and inflammatory cytokines in the plasma of patients with liver cirrhosis were investigated. A retrospective analysis of 68 patients with liver cirrhosis who underwent hepatectomy in the Hunan Provincial People's Hospital from March 2016 to July 2018 was made. According to different anesthesia methods, 30 patients anesthetized with propofol were enrolled into Group A. The other 38 patients anesthetized with propofol combined with remifentanil were enrolled into Group B, and the operation time, amount of bleeding during operation and postoperative awake time of the two groups were recorded. At three separate time-points T1 (30 min before the anesthesia), T2 (after the portal triad clamping), T3 (3 days after the operation), aspartate transaminase (AST) and alanine transaminase (ALT) levels in the plasma were measured by rate method, and the levels of NO, ET-1, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in plasma were detected by enzyme-linked immunosorbent assay (ELISA). The plasma NO levels at the T2 time-point were significantly lower than those at the T1 and T3 time-points (P<0.05); at the T2 time-point, the concentrations of AST, ALT, ET-1, IL-6 and TNF-α in the plasma in Group A were significantly higher than those of Group B (P<0.05), while the levels of plasma NO in Group A were the opposite (P<0.05). The anesthesia of propofol combined with remifentanil could contribute to the balance of NO/ET-1 and the inhibition of inflammatory factors during the hepatectomy operation in patients with liver cirrhosis, and help to protect the liver function of patients, reducing the incidence of liver ischemia-reperfusion injury in patients.

Dexmedetomidine alleviates hepatic injury via the inhibition of oxidative stress and activation of the Nrf2/HO-1 signaling pathway.

Dexmedetomidine (Dex), frequently used as an effective sedative, was reported to play a critical role in the protection of multiple organs. However, its underlying mechanism of a putative protective effect on ischemia/reperfusion (I/R)-induced liver injury is still unclear. A hepatocyte injury model was established by treating WRL-68 cells with oxygen and glucose deprivation/reoxygenation (OGD/R). Enzyme Linked Immunosorbent Assay (ELISA) kits were used to determine the level of inflammatory factors (IL-6, IL-1ß, and TNF-α), and oxidative stress indicators (ROS, MDA, GSH-Px, and SOD). MTT assay and flow cytometry analysis were used to determine the influence of Dex on cell viability and cell apoptosis. Expression of nuclear factor erythroid-derived 2- like 2 (Nrf2), HO-1, and apoptosis-related proteins (Bax, Bcl-2, caspase3, and caspase9) were detected by qRT-PCR and western blotting. Dex promoted cell viability and suppressed cell apoptosis in OGD/R-treated WRL-68 cells. Dex reduced TNF-α, IL-6, IL-1ß, ROS, and MDA production, whereas it increased that of SOD and GSH-Px in OGD/R-treated WRL-68 cells. Moreover, Nrf2, HO-1, and Bcl-2 expression was upregulated, whereas, in contrast, transcripts for Bax, caspase3, and caspase9 were downregulated following Dex treatment under OGD/R. Knockdown of Nrf2 reversed the Dex effects on cell proliferation, apoptosis, and expression of TNF-α, IL-6, IL-1ß, ROS, MDA, SOD, and GSH-Px. Dex protects WRL-68 cells against OGD/R-induced injury by inhibiting inflammation, oxidative stress, and cell apoptosis via the activation of Nrf2/HO-1 signaling pathway, suggesting that Dex may be a potential protector against hepatic injury.

Protective role of LRRC3B in preventing breast cancer metastasis and recurrence post-bupivacaine.

The present study aimed to investigate the potential effect of leucine-rich repeat containing 3B (LRRC3B) with respect to the inhibition of breast cancer recurrence and metastasis post-anesthesia. The mRNA expression of LRRC3B in breast MDA-MB-231 and MCF-7 cell lines was detected using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. The effect of bupivacaine on breast cancer cell invasion was analyzed using a Matrigel assay. LRRC3B specific small interfering (si)RNA was constructed and transfected into breast cancer cells using Lipofectamine® 2000 reagent. The influence of bupivacaine on LRRC3B expression was measured based on RT-qPCR. Additionally, the effect of LRRC3B silencing on the invasion of breast cancer cells treated with bupivacaine was analyzed. Compared with the control, LRRC3B expression significantly increased in MDA-MB-231 and in MCF-7 cells as the length of time increased (P<0.05), but the expression of the gene significantly declined in 2 types of cancer cell when the cells were transfected with siRNA-LRRC3B plasma (P<0.05). The administration of 50 µg/ml bupivacaine promoted maximum breast cancer cell invasion, and suppressed LRRC3B mRNA expression in cells. However, when LRRC3B was silenced in cancer cells, 20 µg/ml bupivacaine significantly promoted cancer cell invasion, indicating that bupivacaine suppresses the expression of LRRC3B and promotes cell invasion. The present study suggested that LRRC3B serves a protective role in preventing bupivacaine-induced breast cancer recurrence and metastasis.

Propofol inhibits expression of angiotensin II receptor type 2 in dorsal root ganglion neurons.

The renin-angiotensin system (RAS) is involved in nociception and has functions in the cardiovascular system. The primary role of the RAS is to mediate the effect of angiotensin II (Ang II) through Ang II receptor type 2 (AT2). Due to this, AT2 has become a novel therapeutic target for the relief of peripheral neuropathic pain in humans. As it is one of the most popular induction agents of general anesthesia, propofol also exerts peripheral antinociceptive effects. The present study assessed the effect of propofol on the expression of AT2 in cultured dorsal root ganglion (DRG) neurons. The results indicate that propofol decreases AT2 mRNA expression in a statistically significant dose- and time-dependent manner (P<0.05). This resulted in a marked decrease in AT2 protein expression and the density of Ang II-binding AT2 on the cell membrane of DRG neurons. The effect of propofol was reversed by LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor. Although propofol exhibited no significant effect on AT2 gene promoter activity, it significantly decreased the stability of AT2 mRNA (P<0.05). However, this effect was reversed by LY294002. In addition, propofol increased PI3K activity in a concentration-dependent manner in DRG neurons. In conclusion, to the best of our knowledge, the current study provides the first evidence suggesting that propofol inhibits the expression of AT2 in DRG neurons by decreasing the stability of AT2 mRNA through a PI3K-dependent mechanism. The present study provides novel insights into the mechanisms of the peripheral antinociceptive action of propofol and suggests a potential means of regulating Ang II/AT2 signaling in the peripheral nervous system.

Anesthetic management of a patient with localised scleroderma.

INTRODUCTION: Scleroderma is a progressive fibrotic disorder of connective tissue which can present multiple anesthetic challenges to anesthetists, especially airway management. Awake intubation with fiberoptic bronchoscope is widely accepted and implemented for progressive systematic scleroderma patients. With the development and improvement of intubation devices these years, there is no report addressing other intubation methods for sclerotic patients. CASE DESCRIPTION: A 47 year-old, 42-kg man with 1-year history of localized scleroderma was scheduled for the operation of inner fixation after 6 days of his acetabular fracture. With careful pre-anesthesia assessment, we chose general anesthesia and intubated the patient with Shikani optical stylet under rapid sequence introduction successfully. DISCUSSION: Scleroderma is a multisystem disease that can affect every aspect of anesthesia especially airway management, which can pose a significant challenge for anesthesiologists. As a result, understanding its pathophysiological changes and implementing a meticulous pre-anesthesia check-up are essential when making an anesthetic plan. CONCLUSION: Anesthetists should have a thorough consideration of all the patho-physiological changes in patients with scleroderma, so as to make a full preparation peri-operatively. Shikani optical stylet may become an alternation for difficult airway in patients with scleroderma.