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2.
J Transl Med ; 22(1): 316, 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38549133

ABSTRACT

BACKGROUND: Propofol is a widely used anesthetic and sedative, which has been reported to exert an anti-inflammatory effect. TLR4 plays a critical role in coordinating the immuno-inflammatory response during sepsis. Whether propofol can act as an immunomodulator through regulating TLR4 is still unclear. Given its potential as a sepsis therapy, we investigated the mechanisms underlying the immunomodulatory activity of propofol. METHODS: The effects of propofol on TLR4 and Rab5a (a master regulator involved in intracellular trafficking of immune factors) were investigated in macrophage (from Rab5a-/- and WT mice) following treatment with lipopolysaccharide (LPS) or cecal ligation and puncture (CLP) in vitro and in vivo, and peripheral blood monocyte from sepsis patients and healthy volunteers. RESULTS: We showed that propofol reduced membrane TLR4 expression on macrophages in vitro and in vivo. Rab5a participated in TLR4 intracellular trafficking and both Rab5a expression and the interaction between Rab5a and TLR4 were inhibited by propofol. We also showed Rab5a upregulation in peripheral blood monocytes of septic patients, accompanied by increased TLR4 expression on the cell surface. Propofol downregulated the expression of Rab5a and TLR4 in these cells. CONCLUSIONS: We demonstrated that Rab5a regulates intracellular trafficking of TLR4 and that propofol reduces membrane TLR4 expression on macrophages by targeting Rab5a. Our study not only reveals a novel mechanism for the immunomodulatory effect of propofol but also indicates that Rab5a may be a potential therapeutic target against sepsis.


Subject(s)
Propofol , Sepsis , Mice , Humans , Animals , Propofol/pharmacology , Propofol/therapeutic use , Propofol/metabolism , Toll-Like Receptor 4/metabolism , Disease Models, Animal , Macrophages/metabolism , Sepsis/complications , Lipopolysaccharides/pharmacology , Lipopolysaccharides/metabolism
3.
J Clin Anesth ; 95: 111439, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38471194

ABSTRACT

STUDY OBJECTIVE: To determine the sex-specific associations between postoperative haemoglobin and mortality or complications reflecting ischaemia or inadequate oxygen supply after major noncardiac surgery. DESIGN: A retrospective cohort study with prospective validation. SETTING: A large university hospital health system in China. PATIENTS: Men and women undergoing elective major noncardiac surgery. INTERVENTIONS AND MEASUREMENTS: The primary exposure was nadir haemoglobin within 48 h after surgery. The outcome of interest was a composite of postoperative mortality or ischaemic events including myocardial injury, acute kidney injury and stroke within hospitalisation. MAIN RESULTS: The study included 26,049 patients (15,757 men and 10,292 women). Low postoperative haemoglobin was a strong predictor of the composite outcome in both sexes, with the risk progressively increasing as the nadir haemoglobin concentration dropped below 130 g l-1 in men and 120 g l-1 in women (adjusted odds ratio [OR] 1.43, 95% CI 1.37-1.50 in men, and OR 1.45, 95% CI 1.35-1.55 in women, per 10 g l-1 decrease in postoperative nadir haemoglobin). Above these sex-specific thresholds, the change of nadir haemoglobin was no longer associated with odds of the composite outcome in either men or women. There was no significant interaction between patient sex and the association between postoperative haemoglobin and the composite outcome (Pinteraction = 0.673). Validation in an external prospective cohort (n = 2120) with systematic postoperative troponin and creatinine measurement confirmed our findings. CONCLUSIONS: Postoperative haemoglobin levels following major noncardiac surgery were nonlinearly associated with ischaemic complications or mortality, without any clinically important interaction with patient sex.


Subject(s)
Anemia , Hemoglobins , Postoperative Complications , Humans , Male , Female , Hemoglobins/analysis , Middle Aged , Anemia/etiology , Anemia/epidemiology , Anemia/blood , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Postoperative Complications/blood , Retrospective Studies , Aged , Sex Factors , China/epidemiology , Prospective Studies , Cohort Studies , Adult , Acute Kidney Injury/etiology , Acute Kidney Injury/epidemiology , Acute Kidney Injury/blood , Elective Surgical Procedures/adverse effects , Surgical Procedures, Operative/adverse effects , Ischemia/etiology , Stroke/etiology , Stroke/epidemiology
4.
Br J Anaesth ; 2024 Mar 24.
Article in English | MEDLINE | ID: mdl-38527923

ABSTRACT

BACKGROUND: Numerous models have been developed to predict acute kidney injury (AKI) after noncardiac surgery, yet there is a lack of independent validation and comparison among them. METHODS: We conducted a systematic literature search to review published risk prediction models for AKI after noncardiac surgery. An independent external validation was performed using a retrospective surgical cohort at a large Chinese hospital from January 2019 to October 2022. The cohort included patients undergoing a wide range of noncardiac surgeries with perioperative creatinine measurements. Postoperative AKI was defined according to the Kidney Disease Improving Global Outcomes creatinine criteria. Model performance was assessed in terms of discrimination (area under the receiver operating characteristic curve, AUROC), calibration (calibration plot), and clinical utility (net benefit), before and after model recalibration through intercept and slope updates. A sensitivity analysis was conducted by including patients without postoperative creatinine measurements in the validation cohort and categorising them as non-AKI cases. RESULTS: Nine prediction models were evaluated, each with varying clinical and methodological characteristics, including the types of surgical cohorts used for model development, AKI definitions, and predictors. In the validation cohort involving 13,186 patients, 650 (4.9%) developed AKI. Three models demonstrated fair discrimination (AUROC between 0.71 and 0.75); other models had poor or failed discrimination. All models exhibited some miscalibration; five of the nine models were well-calibrated after intercept and slope updates. Decision curve analysis indicated that the three models with fair discrimination consistently provided a positive net benefit after recalibration. The results were confirmed in the sensitivity analysis. CONCLUSIONS: We identified three models with fair discrimination and potential clinical utility after recalibration for assessing the risk of acute kidney injury after noncardiac surgery.

5.
Anesth Analg ; 137(5): 1019-1028, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37713328

ABSTRACT

BACKGROUND: Preoperative anemia is an established risk factor for morbidity and mortality after surgery. Men and women have different hemoglobin concentrations and are at different risks of postoperative complications. However, sex-stratified analysis on the association between preoperative hemoglobin and outcomes after noncardiac surgery has been limited in previous studies. METHODS: This was a retrospective cohort study of adult patients undergoing elective major noncardiac surgery in a large academic hospital. The primary outcome was a collapsed composite of postoperative mortality or cardiovascular, renal, pulmonary, and infectious complications during hospitalization. Sex-specific univariable associations between preoperative hemoglobin and the composite outcome were visualized using moving-average and cubic-spline smoothing plots. Multivariable regression models adjusting for patient demographics, comorbidities, medication uses, laboratory tests, and anesthesia/surgery features were used to estimate confounder-adjusted associations. Restricted cubic spline and piecewise linear functions were used to assess the possible nonlinear relationships between preoperative hemoglobin and the outcomes. The interaction between patient sex and hemoglobin on outcomes was assessed using a likelihood-ratio test. RESULTS: We included 22,550 patients, with 6.7% (622 of 9268) of women and 9.7% (1293 of 13,282) of men developing the primary outcome. Lower preoperative hemoglobin was associated with a higher incidence of the primary composite outcome in both men and women. Nonlinearity for the association was not statistically significant in either women ( P = .539) or men ( P = .165). The multivariable-adjusted odds ratios per 1 g/dL increase in hemoglobin were 0.93 (95% confidence interval [CI], 0.87-0.98; P = .013) for women and 0.94 (95% CI, 0.90-0.97; P < .001) for men, with no interaction by sex ( Pinteraction = .923). No hemoglobin thresholds were confirmed at which the associations with the primary outcome changed significantly. CONCLUSIONS: Low preoperative hemoglobin was associated with a higher risk of complications or mortality after elective noncardiac surgery in both men and women. No differences in the strength of associations between sexes were found. Further studies are needed to assess whether these associations are linear or there are sex-specific thresholds of preoperative hemoglobin concentrations below which postoperative risks begin to increase.

6.
J Surg Res ; 287: 72-81, 2023 07.
Article in English | MEDLINE | ID: mdl-36870304

ABSTRACT

INTRODUCTION: The clinical importance of postoperative acute kidney injury (AKI) in patients undergoing general thoracic surgery is unclear. We aimed to systematically review the incidence, risk factors, and prognostic implications of AKI as a complication after general thoracic surgery. METHODS: We searched PubMed, EMBASE, and the Cochrane Library from January 2004 to September 2021. Observational or interventional studies that enrolled ≥50 patients undergoing general thoracic surgery and reported postoperative AKI defined using contemporary consensus criteria were included for meta-analysis. RESULTS: Thirty-seven articles reporting 35 unique cohorts were eligible. In 29 studies that enrolled 58,140 consecutive patients, the pooled incidence of postoperative AKI was 8.0% (95% confidence interval [CI]: 6.2-10.0). The incidence was 3.8 (2.0-6.2) % after sublobar resection, 6.7 (4.1-9.9) % after lobectomy, 12.1 (8.1-16.6) % after bilobectomy/pneumonectomy, and 10.5 (5.6-16.7) % after esophagectomy. Considerable heterogeneity in reported incidences of AKI was observed across studies. Short-term mortality was higher (unadjusted risk ratio: 5.07, 95% CI: 2.99-8.60) and length of hospital stay was longer (weighted mean difference: 3.53, 95% CI: 2.56-4.49, d) in patients with postoperative AKI (11 studies, 28,480 patients). Several risk factors for AKI after thoracic surgery were identified. CONCLUSIONS: AKI occurs frequently after general thoracic surgery and is associated with increased short-term mortality and length of hospital stay. For patients undergoing general thoracic surgery, AKI may be an important postoperative complication that needs early risk evaluation and mitigation.


Subject(s)
Acute Kidney Injury , Thoracic Surgery , Thoracic Surgical Procedures , Humans , Thoracic Surgical Procedures/adverse effects , Pneumonectomy , Risk Factors , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Postoperative Complications/epidemiology , Postoperative Complications/etiology
7.
Cell Rep Med ; 4(3): 100979, 2023 03 21.
Article in English | MEDLINE | ID: mdl-36948152

ABSTRACT

There are significant differences in the susceptibility of populations to intestinal ischemia/reperfusion (I/R), but the underlying mechanisms remain elusive. Here, we show that mice exhibit significant differences in susceptibility to I/R-induced enterogenic sepsis. Notably, the milnacipran (MC) content in the enterogenic-sepsis-tolerant mice is significantly higher. We also reveal that the pre-operative fecal MC content in cardiopulmonary bypass patients, including those with intestinal I/R injury, is associated with susceptibility to post-operative gastrointestinal injury. We reveal that MC attenuates mouse I/R injury in wild-type mice but not in intestinal epithelial aryl hydrocarbon receptor (AHR) gene conditional knockout mice (AHRflox/flox) or IL-22 gene deletion mice (IL-22-/-). Collectively, our results suggest that gut microbiota affects susceptibility to I/R-induced enterogenic sepsis and that gut microbiota-derived MC plays a pivotal role in tolerance to intestinal I/R in an AHR/ILC3/IL-22 signaling-dependent manner, revealing the pathological mechanism, potential prevention and treatment drugs, and treatment strategies for intestinal I/R.


Subject(s)
Gastrointestinal Microbiome , Reperfusion Injury , Mice , Animals , Reperfusion Injury/drug therapy , Reperfusion Injury/pathology , Signal Transduction , Mice, Knockout , Ischemia
8.
Int Urol Nephrol ; 55(10): 2647-2656, 2023 Oct.
Article in English | MEDLINE | ID: mdl-36964822

ABSTRACT

PURPOSE: To examine the relationship between Neutrophil-Lymphocyte Ratio (NLR) and Acute Kidney Injury (AKI) in patients undergoing noncardiac surgery, and subgroup analysis was performed for different types of non-cardiac surgery. METHODS: The present retrospective cohort study included 10,159 adult patients who underwent major noncardiac surgery at Nanfang Hospital, Southern Medical University, between 2008 and 2018. Postoperative AKI was defined as an increase in serum creatinine level of at least 0.3 mg/dl within 48 h, or 1.5 times higher than baseline within 7 days postoperatively according to the Kidney Disease Improving Global Outcome. The correlation between preoperative NLR and postoperative AKI was determined by stepwise multivariate logistic regression analysis, and the predictive value of NLR was evaluated by the receiver operating characteristics curve (ROC) analysis. RESULTS: Four hundred and eighty-five (4.77%) patients developed AKI postoperatively. Preoperative NLR was independently associated with postoperative AKI in all patients undergoing non-cardiac surgery (Odds ratio [OR], 1.03; 95% confidence interval [CI], 1.00-1.06). The optimal cut-off value of NLR was 2.12 according ROC analysis. The OR and 95% CI of AKI for NLR > 2.12 was 1.48 (1.21-1.81) compared with NLR ≤ 2.12. In addition, the positive association was mainly shown in patients undergone digestive system surgery with a cut-off value of 2.12 but not in neurological and musculoskeletal system surgeries. CONCLUSION: The present study confirmed the association of preoperative NLR with postoperative AKI in digestive system surgical patients. A NLR value of 2.12 may be a useful cut-off to evaluate the risk of AKI.


Subject(s)
Acute Kidney Injury , Neutrophils , Adult , Humans , Retrospective Studies , Lymphocytes , ROC Curve , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology , Postoperative Complications/etiology , Risk Factors
9.
J Med Virol ; 95(1): e28267, 2023 01.
Article in English | MEDLINE | ID: mdl-36319439

ABSTRACT

BACKGROUND: Myocardial injury is a major complication of sepsis and a key factor affecting prognosis. Therefore, early and accurate diagnosis and timely management of sepsis-induced cardiomyopathy (SICM) are of great significance for the prevention and treatment of sepsis. The gut microbiota has been shown to be closely associated with sepsis or myocardial injury, but the association between the gut microbiota and SICM is not fully understood. This study aimed to explore the link between gut microbiota composition and SICM. METHODS: A case-control and single-center study of clinical features and gut microbiota profiles by Metagenome and Virome was conducted in SICM patients (n = 15) and sepsis-uninduced cardiomyopathy patients (SNICM, n = 16). RESULTS: Compared with SNICM patients, SICM patients showed significant myocardial injury and higher 28-day mortality, SOFA scores, lactate levels, and infection levels on admission. Meanwhile, differences in the composition of gut bacteria, archaea, fungi, and viruses were analyzed between the two groups. Differential gut bacteria or viruses were found to have a good predictive effect on SICM. Furthermore, gut bacteria and viruses that differed between the two groups were strongly related. The abundance of Cronobacter and Cronobacter phage was higher in the SICM group than in the SNICM group, and the receiver operating characteristic curve showed that Cronobacter and Cronobacter phage both had a good predictive effect on SICM. CONCLUSIONS: SICM patients may have specific gut microbiota signatures, and Cronobacter and Cronobacter phages have a good ability to identify and diagnose SICM.


Subject(s)
Bacteriophages , Cardiomyopathies , Gastrointestinal Microbiome , Sepsis , Humans , Case-Control Studies , Dysbiosis/complications , Cardiomyopathies/etiology , Bacteria/genetics , Sepsis/complications
10.
Ann Transl Med ; 10(21): 1161, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36467356

ABSTRACT

Background: Intestinal ischemia-reperfusion (I/R) injury is a serious condition with unacceptable mortality rates. Our previous study revealed a protective effect of dexmedetomidine (DEX) on intestinal I/R injury, but its underlying mechanism remains unclear. Gut microbiota imbalance is associated with the progression of I/R injury. We hypothesized that DEX would attenuate intestinal I/R injury via modulating gut microbiota. Methods: An I/R injury model was established in C57BL/6 mice in the presence or absence of DEX preconditioning. Some mice were treated with antibiotics to deplete intestinal bacteria. Fecal microbiota transplantation (FMT) was performed by transplanting the feces of DEX-pretreated mice into a new batch of I/R mice. We analyzed the expression of Bacteroidetes and Firmicutes in feces, survival rate, and inflammatory cytokines. Results: DEX reversed I/R-induced bacterial abnormalities by increasing the ratio of Firmicutes to Bacteroidetes [DEX + I/R 3.02±0.36 vs. normal saline (NS) + I/R 0.82±0.15; 95% CI: 0.80-3.60; P<0.05] and was accompanied by increased 72-hour survival (0.40±0.16 vs. 0.10±0.09; P<0.05). The protective effect of DEX did not significantly differ from that of DEX + antibiotics. Furthermore, the bacteria of the DEX-pretreated mice decreased the release of inflammatory factors. Conclusions: This study revealed that DEX can alleviate intestinal I/R injury through a microbiota-related mechanism, providing a potential avenue for the management of intestinal I/R injury.

11.
Anesth Analg ; 135(6): e48-e49, 2022 12 01.
Article in English | MEDLINE | ID: mdl-36384020
13.
Front Cell Infect Microbiol ; 12: 857035, 2022.
Article in English | MEDLINE | ID: mdl-35372123

ABSTRACT

Objective: Sepsis-induced myocardial dysfunction (SIMD) seriously affects the evolution and prognosis of the sepsis patient. The gut microbiota has been confirmed to play an important role in sepsis or cardiovascular diseases, but the changes and roles of the gut microbiota in SIMD have not been reported yet. This study aims to assess the compositions of the gut microbiota in sepsis or septic patients with or without myocardial injury and to find the relationship between the gut microbiota and SIMD. Methods: The prospective, observational, and 1:1 matched case-control study was conducted to observe gut microbiota profiles from patients with SIMD (n = 18) and matched non-SIMD (NSIMD) patients (n = 18) by 16S rRNA gene sequencing. Then the relationship between the relative abundance of microbial taxa and clinical indicators and clinical outcomes related to SIMD was analyzed. The receiver operating characteristic (ROC) curves were used to evaluate the predictive efficiencies of the varied gut microbiota to SIMD. Results: SIMD was associated with poor outcomes in sepsis patients. The beta-diversity of the gut microbiota was significantly different between the SIMD patients and NSIMD subjects. The gut microbiota profiles in different levels significantly differed between the two groups. Additionally, the abundance of some microbes (Klebsiella variicola, Enterobacteriaceae, and Bacteroides vulgatus) was correlated with clinical indicators and clinical outcomes. Notably, ROC analysis indicated that K. variicola may be a potential biomarker of SIMD. Conclusion: Our study indicates that SIMD patients may have a particular gut microbiota signature and that the gut microbiota might be a potential diagnostic marker for evaluating the risk of developing SIMD.


Subject(s)
Sepsis , Shock, Septic , Case-Control Studies , Dysbiosis/complications , Humans , Prospective Studies , RNA, Ribosomal, 16S/genetics , Sepsis/complications , Shock, Septic/complications
15.
Anesth Analg ; 134(4): 699-709, 2022 04 01.
Article in English | MEDLINE | ID: mdl-34403381

ABSTRACT

BACKGROUND: Evidence suggests a potential relationship between gut microbiota and chronic postoperative pain (CPP). This study aimed to explore the predictive and preventive potential of preoperative gut microbiota in CPP in breast cancer survivors. METHODS: In the clinical experiments, we designed a nested case-control study to compared preoperative gut microbiota of breast cancer survivors with and without CPP using 16s rRNA sequencing. The primary outcome was clinically meaningful pain in or around the operative area 3 months after surgery. Logistic prediction models based on previously identified risk factors for CPP in breast cancer survivors were tested with and without differential bacteria to evaluate the model's potential for improvement with the addition of gut microbiota information. In the animal experiments, preoperative fecal microbiota was transplanted from patients with and without CPP to mice, and a spared nerve injury (SNI) model was used to mimic neuropathic pain in CPP. Mechanical hyperalgesia and the expression of markers of spinal microglia and peroxisome proliferator-activated receptor-γ (PPAR-γ) were assessed. RESULTS: Sixty-six CPP patients and 66 matched controls were analyzed. Preoperative gut microbiota composition was significantly different in the 2 groups at phylus, family, and genera levels. The discrimination of the clinical prediction model (determined by area under the receiver operating characteristic curve) improved by 0.039 and 0.099 after the involvement of differential gut microbiota at the family and genus levels, respectively. After fecal microbiota transplantation (FMT), "CPP microbiota" recipient mice exhibited significantly increased mechanical hyperalgesia and decreased expression of Ppar-γ and arginase-1 (Arg-1) in the spinal cord. CONCLUSIONS: Preoperative gut microbiota has the potential to predict and prevent the development of CPP and plays a causal role in its development via the PPAR-γ-microglia pathway in the spinal cord. Thus, it could be targeted to develop a prevention strategy for CPP in breast cancer survivors.


Subject(s)
Breast Neoplasms , Cancer Survivors , Gastrointestinal Microbiome , Animals , Breast Neoplasms/surgery , Case-Control Studies , Female , Humans , Hyperalgesia , Mice , Models, Statistical , Pain, Postoperative/diagnosis , Pain, Postoperative/etiology , Pain, Postoperative/prevention & control , Peroxisome Proliferator-Activated Receptors , Prognosis , RNA, Ribosomal, 16S/genetics
16.
Front Immunol ; 12: 704836, 2021.
Article in English | MEDLINE | ID: mdl-34650552

ABSTRACT

Intestinal ischemia/reperfusion (I/R) injury is a grave condition with high morbidity and mortality. We previously confirmed that intestinal I/R induces intestinal flora disorders and changes in metabolites, but the role of different metabolites in intestinal I/R injury is currently unclear. Based on targeted metabolic sequencing, pravastatin (PA) was determined to be a metabolite of the gut microbiota. Further, intestinal I/R model mice were established through superior mesenteric artery obstruction. In addition, a co-culture model of small intestinal organoids and type II innate lymphoid cells (ILC2s) was subjected to hypoxia/reoxygenation (H/R) to simulate an intestinal I/R model. Moreover, correlation analysis between the PA level in preoperative feces of patients undergoing cardiopulmonary bypass and the indices of postoperative intestinal I/R injury was carried out. IL-33-deficient mice, ILC2-deleted mice, and anti-IL-13 neutralizing antibodies were also used to explore the potential mechanism through which PA attenuates intestinal I/R injury. We demonstrated that PA levels in the preoperative stool of patients undergoing cardiopulmonary bypass were negatively correlated with the indices of postoperative intestinal I/R injury. Furthermore, PA alleviated intestinal I/R injury and improved the survival of mice. We further showed that PA promotes IL-13 release from ILC2s by activating IL-33/ST2 signaling to attenuate intestinal I/R injury. In addition, IL-13 promoted the self-renewal of intestinal stem cells by activating Notch1 and Wnt signals. Overall, results indicated that the gut microbial metabolite PA can attenuate intestinal I/R injury by promoting the release of IL-13 from ILC2s via IL-33/ST2 signaling, revealing a novel mechanism of and therapeutic strategy for intestinal I/R injury.


Subject(s)
Gastrointestinal Microbiome/immunology , Immunity, Innate , Interleukin-1 Receptor-Like 1 Protein/immunology , Interleukin-13/immunology , Interleukin-33/immunology , Intestinal Diseases/immunology , Lymphocytes/immunology , Pravastatin/immunology , Animals , Disease Models, Animal , Humans , Interleukin-1 Receptor-Like 1 Protein/genetics , Interleukin-13/genetics , Interleukin-33/genetics , Intestinal Diseases/genetics , Male , Mice , Mice, Knockout , Reperfusion Injury
17.
J Leukoc Biol ; 110(6): 1131-1142, 2021 12.
Article in English | MEDLINE | ID: mdl-34402106

ABSTRACT

Traumatic spinal cord injury (SCI) is a devastating condition marked by permanent motor, sensory, and autonomic dysfunction, in which the inflammatory response serves an important and preventable role. High mobility group box-1 (HMGB1) is a potent regulator of inflammation in numerous acute and chronic inflammatory conditions.; however, the role of HMGB1 in SCI remains unclear. The present study aimed to characterize the temporal dynamics of HMGB1 release after SCI, to investigate the role of spinal microglia activation in mediating the effects of HMGB1 on SCI, and to explore the therapeutic potential of intrathecal anti-HMGB1 polyclonal antibody on alleviating SCI. The present study demonstrated that HMGB1 expression was increased immediately after traumatic injury of a primary spinal neuron culture. It was found that neutralizing HMGB1 significantly ameliorated SCI pathogenesis and hind limb paralysis. Moreover, the levels of a number of pro-inflammatory cytokines in the SCI lesion were reduced when local HMGB1 was blocked by anti-HMGB1 antibody. In addition, the injured neuron-derived conditioned medium increased TNF-α secretion and the NF-κB pathway in the BV2 microglia cell line via HMGB1. Collectively, these results indicated that HMGB1 served an important role in SCI inflammation and suggested the therapeutic potential of an anti-HMGB1 antibody for SCI.


Subject(s)
HMGB1 Protein/immunology , HMGB1 Protein/metabolism , Spinal Cord Injuries/immunology , Spinal Cord Injuries/metabolism , Animals , Cytokines/biosynthesis , Female , Inflammation/immunology , Inflammation/metabolism , Microglia/metabolism , Rats , Rats, Sprague-Dawley
18.
Clin Exp Pharmacol Physiol ; 48(9): 1203-1214, 2021 09.
Article in English | MEDLINE | ID: mdl-34042207

ABSTRACT

One-lung ventilation (OLV), a common ventilation technique, is associated with perioperative lung injury, tightly connected with inflammatory responses. Dexmedetomidine has shown positive anti-inflammatory effects in lung tissues in pre-clinical models. This study investigated the efficacy of dexmedetomidine for suppressing inflammatory responses in patients requiring OLV. We searched PubMed, MEDLINE, Embase, Scopus, Ovid, and Cochrane Library for randomized controlled trials focusing on dexmedetomidine's anti-inflammatory effects on patients requiring OLV without any limitation on the year of publication or languages. 20 clinical trials were assessed with 870 patients in the dexmedetomidine group and 844 in the control group. Our meta-analysis investigated the anti-inflammatory property of dexmedetomidine perioperatively [T1 (30-min OLV), T2 (90-min OLV), T3 (end of surgery) and T4 (postoperative day 1)], demonstrating that dexmedetomidine's intraoperative administration resulted in a significant reduction in serum concentration of interleukin-6, tumor necrosis factor-α and other inflammatory cytokines perioperatively. By calculating specific I2 index, significant heterogeneity was observed on all occasions, with I2 index ranging from 95% to 99%. For IL-6 changes, sensitivity analysis showed that the exclusion of a single study led to a significant decrease of heterogeneity (96%-0%; p < 0.00001). Besides, pulmonary oxygenation was ameliorated in the dexmedetomidine group comparing with the control group. In conclusion, perioperative administration of dexmedetomidine can attenuate OLV induced inflammation, ameliorate pulmonary oxygenation, and may be conducive to a decreased occurrence of postoperative complications and better prognosis. However, the results should be prudently interpreted due to the evidence of heterogeneity and the limited number of studies.


Subject(s)
Lung Injury
19.
Scanning ; 2021: 5530788, 2021.
Article in English | MEDLINE | ID: mdl-34025899

ABSTRACT

Coating treatment plays an irreplaceable role in propelling the clinical application of magnesium alloys. This experiment was designed in order to observe the anticorrosion behavior of magnesium fluoride coating in rats. The MgF2 layer was prepared on the surface of AZ31 magnesium alloy in saturated NH4HF2 solution by microarc fluorination (MAF) at 190 V. The cross-sectional SEM, EDS, and XRD analysis indicated that the alloy surface was covered with MgF2. Meanwhile, SEM observation was used to compare the magnesium alloy samples before and after treatment, and it was found that the samples after coating were flatter and smoother. Two sets of experiments were carried out with the subjects, 6-week-old male rats. So that the untreated AZ31 samples and the microarc fluorinated AZ31 samples could be buried under the muscle layer individually. The volume changes and surface morphology of the corroded samples were monitored dynamically using micro-CT over a 16-week period in vivo. Comparison of results between the two sets of samples presented that the corrosion of the microarc fluoridated samples was much slower than that of the untreated ones. The MAF coating was shown to be effective in controlling the corrosion rate and progression of the magnesium alloy.


Subject(s)
Halogenation , Magnesium , Alloys , Animals , Coated Materials, Biocompatible , Corrosion , Cross-Sectional Studies , Male , Rats
20.
Scanning ; 2021: 5574946, 2021.
Article in English | MEDLINE | ID: mdl-34055130

ABSTRACT

In the ongoing research on the application of biodegradable materials, surface treatment of is considered to be a relatively effective solution to the excessive degradation rates of Mg alloys. In this study, to further optimize the proven effective surface coatings of fluoride, a low-voltage preparation fluorination method was used to achieve coating effectiveness under safer conditions. Optical observation, scanning electron microscopy (SEM), X-ray diffraction (XRD), energy-dispersive spectroscopy (EDS), and potential dynamic polarization (PDP) experiments were used for the analysis and evaluation. The coating characteristics of the MgF2 coatings treated in the 10-90 V voltage range, including the structure, chemical conformation, and electrochemical corrosion assessment, were fully defined. The anodic fluoridation results showed that a pore structure of 1-14 µm thickness was formed on the Mg alloy substrate, and the coating was composed of Mg fluoride. The results of immersion corrosion and electrochemical corrosion experiments showed that compared with pure Mg, anodic fluorinated samples below 40 V exhibited better corrosion resistance, the prepared MgF2 coating was more uniform, and the surface mostly exhibited point corrosion. When the voltage reached or exceeded 60 V, the prepared coating exhibited poor corrosion resistance, fracture, and protrusions. After corrosion, it mostly exhibited surface corrosion. The results indicate that idealized coatings can be obtained at relatively low and safe voltage ranges. This finding may enable more economical, environmentally friendly, and safe preparation of coatings.

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