Targeting Mitochondria-Inflammation Circuit by ß-Hydroxybutyrate Mitigates HFpEF.

RATIONALE: Over 50% of patients with heart failure have preserved ejection fraction (HFpEF), rather than reduced ejection fraction. Complexity of its pathophysiology and the lack of animal models hamper the development of effective therapy for HFpEF. OBJECTIVE: This study was designed to investigate the metabolic mechanisms of HFpEF and test therapeutic interventions using a novel animal model. METHODS AND RESULTS: By combining the age, long-term high-fat diet, and desoxycorticosterone pivalate challenge in a mouse model, we were able to recapture the myriad features of HFpEF. In these mice, mitochondrial hyperacetylation exacerbated while increasing ketone body availability rescued the phenotypes. The HFpEF mice exhibited overproduction of IL (interleukin)-1ß/IL-18 and tissue fibrosis due to increased assembly of NLPR3 inflammasome on hyperacetylated mitochondria. Increasing ß-hydroxybutyrate level attenuated NLPR3 inflammasome formation and antagonized proinflammatory cytokine-triggered mitochondrial dysfunction and fibrosis. Moreover, ß-hydroxybutyrate downregulated the acetyl-CoA pool and mitochondrial acetylation, partially via activation of CS (citrate synthase) and inhibition of fatty acid uptake. CONCLUSIONS: Therefore, we identify the interplay of mitochondrial hyperacetylation and inflammation as a key driver in HFpEF pathogenesis, which can be ameliorated by promoting ß-hydroxybutyrate abundance.

Efficacy of prolonged intravenous lidocaine infusion for postoperative movement-evoked pain following hepatectomy: a double-blinded, randomised, placebo-controlled trial.

BACKGROUND: The analgesic effect of intravenous lidocaine varies with the duration of lidocaine infusion and surgery type. We tested the hypothesis that prolonged lidocaine infusion alleviates postoperative pain in patients recovering from hepatectomy over the first 3 postoperative days. METHODS: Patients undergoing elective hepatectomy were randomly assigned to receive prolonged i.v. lidocaine treatment or placebo. The primary outcome was incidence of moderate-to-severe movement-evoked pain at 24 h postoperatively. The secondary outcomes included incidence of moderate-to-severe pain during movement and at rest throughout the first 3 postoperative days, postoperative opioid consumption, and pulmonary complications. Plasma lidocaine concentration was also monitored. RESULTS: We enrolled 260 subjects. Intravenous lidocaine lowered the incidence of moderate-to-severe movement-evoked pain at 24 h and 48 h postoperatively (47.7% vs 67.7%, P=0.001; 38.5% vs 58.5%, P=0.001) and reduced movement-evoked pain scores (3.7 [1.7] vs 4.2 [1.6]; mean difference 0.5 [95% confidence interval {CI}: 0.1-0.9]; P=0.018) and morphine equivalent consumption (47.2 [16.7] mg vs 52.6 [19.2] mg; mean difference 5.4 mg [95% CI: 1.0-9.8]; P=0.016) at 24 h postoperatively. Lidocaine also lowered the incidence of postoperative pulmonary complications (23.1% vs 38.5%; P=0.007). Median plasma lidocaine concentrations were 1.5, 1.9, and 1.1 µg ml-1 (inter-quartile ranges: 1.1-2.1, 1.4-2.6, and 0.8-1.6, respectively) after bolus injection, at the end of the surgery, and 24 h postoperatively. CONCLUSIONS: Prolonged intravenous lidocaine infusion reduced the incidence of moderate-to-severe movement-evoked pain for 48 h after hepatectomy. However, the reduction in pain scores and opioid consumption by lidocaine was below the minimal clinically important difference. CLINICAL TRIAL REGISTRATION: NCT04295330.

Appropriate Duration of Perioperative Intravenous Administration of Lidocaine to Provide Satisfactory Analgesia for Adult Patients Undergoing Colorectal Surgery: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Perioperative lidocaine infusion has been reported to alleviate pain intensity after colorectal surgery. However, there is no consensus on whether prolonged lidocaine infusion is more effective than short lidocaine infusion. This meta-analysis aimed to determine an appropriate duration of lidocaine infusion in patients undergoing colorectal surgery. METHODS: We searched the PubMed, EMBASE, Web of Science, and Cochrane Library databases to identify articles published before December 17, 2021. Randomized controlled trials comparing intravenous lidocaine with placebo for pain relief in patients undergoing colorectal surgery were included. The primary outcome was pain scores (visual analog scale [VAS], 0-10 cm) at 24 hours postoperatively at rest and on movement. Secondary outcomes included pain scores at 12, 48, and 72 hours postoperatively, analgesic consumption (mg), gastrointestinal function return (hour), length of hospital stay (days), and incidence of complications. According to the duration of lidocaine infusion, studies were grouped into infusion for at least 24 hours (prolonged lidocaine infusion) and less than 24 hours (short lidocaine infusion) to assess the impact of lidocaine infusion duration on the outcomes of interests. Quantitative analyses were performed using a random effects model. RESULTS: Eleven studies with 548 patients were included. Five studies used prolonged lidocaine infusion, while 6 studies used short lidocaine infusion. Prolonged lidocaine infusion reduced postoperative pain scores versus placebo at 24 hours at rest (mean difference [MD], -0.91 cm; 95% confidence interval [CI], -1.54 to -0.28; P = .02) and on movement (MD, -1.69 cm; 95% CI, -2.15 to -1.22; P < .001), while short lidocaine infusion showed no benefit. Compared with placebo, prolonged lidocaine infusion reduced pain scores at 12 hours at rest and at 12 and 48 hours on movement, but short lidocaine infusion did not. However, there was no significant difference in pain scores between the prolonged and short lidocaine infusion groups at these time points. Compared with placebo, prolonged lidocaine infusion shortened the length of hospital stay (MD, -1.30 days; 95% CI, -1.72 to -0.88; P < .001) and time to first postoperative defecation (MD, -12.51 hours; 95% CI, -22.67 to -2.34; P = .02). There were no differences between groups regarding the other outcomes. CONCLUSIONS: The analgesic effect of intravenous lidocaine may depend on the duration of infusion, and our results suggest that lidocaine infusion should be administered for at least 24 hours after colorectal surgery. Since overall evidence quality was low, further high-quality, large-sample trials are needed to explore an optimal lidocaine infusion strategy in patients undergoing colorectal surgery.

Anaesthetic considerations in Shrinking Man syndrome: two case reports.

BACKGROUND: Shrinking Man syndrome (SMS) is a rare but often serious complication of dialysis-dependent end-stage renal disease, characterized by significant loss of height, bone pain, bone deformity, and skin itching. Patients with SMS always have abnormal facial changes and cardiovascular system damage (manifested by hypertension, hypotension, cardiovascular calcification, and valvular heart disease), which pose a great challenge to anaesthesiologists. The purpose of this report is to describe our anaesthetic experience regarding two patients with SMS combined with alterations of the airway and cardiovascular system. CASE PRESENTATION: We describe two cases of SMS treated at West China Hospital, a tertiary care centre in Chengdu, China. All cases met the diagnostic criteria, which comprised 1) dialysis-dependent end-stage renal disease, 2) loss of height, and 3) bone pain and bone deformity. One patient had an anticipated difficult airway and moderate-to-severe mitral stenosis. The other patient presented with significant hypotension. Anaesthetic considerations included awake fibreoptic bronchoscopy-assisted tracheal intubation, real-time transoesophageal echocardiogram monitoring and individualized blood pressure management strategies. CONCLUSION: This case series highlights the importance of adequate preoperative assessment and preparation, as well as individualized anaesthetic management, in patients with SMS.

[Effect of Pp2cm Gene Silencing on Mouse Macrophage Resistance Against Staphylococcus aureus Infection via TLR Pathway].

Objective: To investigate the effect of silencing protein phosphatase 2cm ( Pp2cm) gene on the expression of inflammatory factors in macrophages infected with Staphylococcus aureus ( S. aureus) and the mechanisms involved. Methods: The effects of Pp2cm knockdown on inflammatory factors, proliferation, apoptosis, and Toll-like receptor (TLR) signaling were analyzed in RAW 264.7 cells, a murine macrophage cell line, transfected with adenovirus (Ad). The cells were divided into four groups, including Ad-Ctrl group, Ad- Pp2cm group, Ad-Ctrl+ S. aureus group and Ad- Pp2cm+ S. aureus group. Cell transfection was achieved by separately introducing control adenovirus (Ad-Ctrl) or adenovirus targeting the Pp2cm gene (Ad- Pp2cm) and inflammation or the absence of inflammation was induced by applying or not applying S. aureus. The expression of tumor necrosis factor-alpha ( TNF-α), interleukin-1ß ( IL-1 ß), TLR2, TLR4, Toll-like receptor adaptor protein ( Tirap) and myeloid differentiation factor 88 ( Myd88) was determined by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). PP2Cm protein expression was determined by Western blot. Cell proliferation was determined by cell counting kit-8 (CCK-8) assay and cell apoptosis was measured by flow cytometry. Results: The expression of Pp2cmgene and PP2Cm protein was downregulated in the Ad- Pp2cm group when compared to the Ad-Ctrl group, with the diference showing statistical significance ( P<0.05). When compared to those of the Ad-Ctrl+ S. aureus group, macrophages in the Ad- Pp2cm+ S. aureus group showed significantly increase in the TNF- α and IL-1 ß gene levels ( P<0.01). Furthermore, the Ad- Pp2cm group demonstrated elevated gene expression levels of TLR2, TLR4, Tirap and Myd88 in macrophages when compared to the Ad-Ctrl group, with the difference showing statistical significance ( P<0.05). There were no statistically significant differences in cell apoptosis and proliferation between the Ad-Ctrl and Ad- Pp2cm groups. Conclusions: Silencing Pp2cm gene promotes the inflammatory response of macrophages to S. aureus infection. Moreover, the TLR pathway plays an important role in the inflammatory activation of macrophages.

Mitochondrial protein hyperacetylation underpins heart failure with preserved ejection fraction in mice.

Over 50% of patients with heart failure have preserved ejection fraction (HFpEF), rather than reduced ejection fraction (HFrEF). The prevalence of HFpEF continues to increase, while the pathogenic mechanisms underlying HFpEF remain largely elusive and evidence-based therapies are still lacking. This study was designed to investigate the metabolic signature of HFpEF and test the potential therapeutic intervention in a mouse model. By utilizing a "3-Hit" HFpEF mouse model, we observed a global protein hyperacetylation in the HFpEF hearts as compared to the pressure overload-induced HFrEF and adult/aged non-heart failure (NHF) hearts. Acetylome analysis identified that a large proportion of the hyperacetylated proteins (74%) specific to the HFpEF hearts are in mitochondria, and enriched in tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS), and fatty acid oxidation. Further study showed that the elevated protein acetylation in the HFpEF hearts was correlated with reduced NAD+/NADH ratio, impaired mitochondrial function, and depleted TCA cycle metabolites. Normalization of NAD+/NADH ratio by supplementation of nicotinamide riboside (NR) for 30 days downregulated the acetylation level, improved mitochondrial function and ameliorated HFpEF phenotypes. Therefore, our study identified a distinct protein acetylation pattern in the HFpEF hearts, and proposed NR as a promising agent in lowering acetylation and mitigating HFpEF phenotypes in mice.

Antibacterial activity of essential oils extracted from the unique Chinese spices cassia bark, bay fruits and cloves.

Spices are widely used in daily life such as diet and have certain activity. Especially in China, spices have been mainly used as condiments for thousands of years in order to improve the sensory quality of food; in addition, they and their derivatives can also be used as preservatives. In this study, three spices with unique Chinese characteristics widely used were selected: cassia bark (bark of Cinnamomum camphora Presl), bay fruits (Laurus nobilis), and cloves (Syzygiumaromaticum). The main components and antibacterial ability of these three spices were analyzed by simulated extraction method. Through headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC-MS) analysis, it was determined that the main active compounds in the essential oils of cassia bark, bay fruits and cloves were cinnamaldehyde (78.11%), cinnamaldehyde (61.78%) and eugenol (75.23%), respectively. The agar plate diffusion test and the simulated food culture medium experiment confirmed that the essential oils extracted from the three flavors have antibacterial effects on Listeria monocytogenes, Listeria innocua, Listeria welshimeri, Listeria ivanovii, Listeria grayi and Vibrio parahaemolyticus. The antibacterial activity of different strains has different optimal extraction conditions. Generally speaking, cinnamon essential oil has the strongest antibacterial activity, while laurel fruit has the lowest antibacterial activity. The study proved the antibacterial activity of these three Chinese-specific spices and provided some new ideas and methods for the subsequent research and preparation of natural food additives and food antibacterial agents.

Comparison of an in-house hybrid DIR method to NiftyReg on CBCT and CT images for head and neck cancer.

An in-house hybrid deformable image registration (DIR) method, which combines free-form deformation (FFD) and the viscous fluid registration method, is proposed. Its results on the planning computed tomography (CT) and the day 1 treatment cone-beam CT (CBCT) image from 68 head and neck cancer patients are compared with the results of NiftyReg, which uses B-spline FFD alone. Several similarity metrics, the target registration error (TRE) of annotated points, as well as the Dice similarity coefficient (DSC) and Hausdorff distance (HD) of the propagated organs at risk are employed to analyze their registration accuracy. According to quantitative analysis on mutual information, normalized cross-correlation, and the absolute pixel value differences, the results of the proposed DIR are more similar to the CBCT images than the NiftyReg results. Smaller TRE of the annotated points is observed in the proposed method, and the overall mean TRE for the proposed method and NiftyReg was 2.34 and 2.98 mm, respectively (p < 0.001). The mean DSC in the larynx, spinal cord, oral cavity, mandible, and parotid given by the proposed method ranged from 0.78 to 0.91, significantly higher than the NiftyReg results (ranging from 0.77 to 0.90), and the HD was significantly lower compared to NiftyReg. Furthermore, the proposed method did not suffer from unrealistic deformations as the NiftyReg did in the visual evaluation. Meanwhile, the execution time of the proposed method was much higher than NiftyReg (96.98 ± 11.88 s vs. 4.60 ± 0.49 s). In conclusion, the in-house hybrid method gave better accuracy and more stable performance than NiftyReg.

TLR4 is required for macrophage efferocytosis during resolution of ventilator-induced lung injury.

Mechanical ventilation is a life-sustaining therapy for patients with respiratory failure but can cause further lung damage known as ventilator-induced lung injury (VILI). However, the intrinsic molecular mechanisms underlying recovery of VILI remain unknown. Phagocytosis of apoptotic cells (also known as efferocytosis) is a key mechanism orchestrating successful resolution of inflammation. Here we show the positive regulation of macrophage Toll-like receptor (TLR) 4 in efferocytosis and resolution of VILI. Mice were depleted of alveolar macrophages and then subjected to injurious ventilation (tidal volume, 20 mL/kg) for 4 h. On day 1 after mechanical ventilation, Tlr4+/+ or Tlr4-/- bone marrow-derived macrophages (BMDMs) were intratracheally administered to alveolar macrophage-depleted mice. We observed that mice depleted of alveolar macrophages exhibited defective resolution of neutrophilic inflammation, exuded protein, lung edema, and lung tissue injury after ventilation, whereas these delayed responses were reversed by administration of Tlr4+/+ BMDMs. Importantly, these proresolving effects by Tlr4+/+ BMDMs were abolished in mice receiving Tlr4-/- BMDMs. The number of macrophages containing apoptotic cells or bodies in bronchoalveolar lavage fluid was much less in mice receiving Tlr4-/- BMDMs than that in those receiving Tlr4+/+ BMDMs. Macrophage TLR4 deletion facilitated a disintegrin and metalloprotease 17 maturation and enhanced Mer cleavage in response to mechanical ventilation. Heat shock protein 70 dramatically increased Mer tyrosine kinase surface expression, phagocytosis of apoptotic neutrophils, and rescued the inflammatory phenotype in alveolar macrophage-depleted mice receiving Tlr4+/+ BMDMs, but not Tlr4-/- BMDMs. Our results suggest that macrophage TLR4 promotes resolution of VILI via modulation of Mer-mediated efferocytosis.

The GTPase Rab1 Is Required for NLRP3 Inflammasome Activation and Inflammatory Lung Injury.

Uncontrolled inflammatory response during sepsis predominantly contributes to the development of multiorgan failure and lethality. However, the cellular and molecular mechanisms for excessive production and release of proinflammatory cytokines are not clearly defined. In this study, we show the crucial role of the GTPase Ras-related protein in brain (Rab)1a in regulating the nucleotide binding domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation and lung inflammatory injury. Expression of dominant negative Rab1 N124I plasmid in bone marrow-derived macrophages prevented the release of IL-1ß and IL-18, NLRP3 inflammasome activation, production of pro-IL-1ß and pro-IL-18, and attenuated TLR4 surface expression and NF-кB activation induced by bacterial LPS and ATP compared with control cells. In alveolar macrophage-depleted mice challenged with cecal ligation and puncture, pulmonary transplantation of Rab1a-inactivated macrophages by expression of Rab1 N124I plasmid dramatically reduced the release of IL-1ß and IL-18, neutrophil count in bronchoalveolar lavage fluid, and inflammatory lung injury. Rab1a activity was elevated in alveolar macrophages from septic patients and positively associated with severity of sepsis and respiratory dysfunction. Thus, inhibition of Rab1a activity in macrophages resulting in the suppression of NLRP3 inflammasome activation may be a promising target for the treatment of patients with sepsis.

Extubation in the operating room results in fewer composite mechanical ventilation-related adverse outcomes in patients after liver transplantation: a retrospective cohort study.

BACKGROUND: To investigate the effect of extubation in the operating room (OR) on mechanical ventilation-related adverse outcomes in patients who undergo liver transplantation. METHODS: Patients who underwent liver transplantation between January 2016 and December 2019 were included. According to the timing of extubation, patients were divided into OR extubation group and intensive care unit (ICU) extubation group. The propensity score was used to match OR extubation group and ICU extubation group at a 1:2 ratio by demographical and clinical covariates. The primary outcome was a composite of mechanical ventilation-related adverse outcomes, including 30-day all-cause mortality, in-hospital acute kidney injury (stage 2 or 3), and in-hospital moderate to severe pulmonary complications. Secondary outcomes included in-hospital moderate to severe infectious complications, unplanned reintubation rates, ICU and postoperative hospital lengths of stay, and total hospital cost. RESULTS: A total of 438 patients were enrolled. After propensity score matching, 94 patients were in OR extubation group and 148 patients were in ICU extubation group. Incidence of the composite mechanical ventilation-related adverse outcomes was significantly lower in OR extubation group than ICU extubation group, even after adjusting for confounding factors (19.1% vs. 31.8%; Odds Ratio, 0.509; 95% Confidence Index [CI], 0.274-0.946; P=0.031). The duration of ICU stay was much shorter in OR extubation group than ICU extubation group (median 4, Interquartile range [IQR] (3 ~ 6) vs. median 6, IQR (4 ~ 8); P<0.001). Meanwhile, extubation in the OR led to a significant reduction of total hospital cost compared with extubation in the ICU (median 3.9, IQR (3.5 ~ 4.6) 10000 US dollars vs. median 4.1, IQR (3.8 ~ 5.1) 10000 US dollars; P=0.021). However, there were no statistically significant differences in moderate to severe infectious complications, unplanned reintubation rates, and the length of postoperative hospital stay between groups. CONCLUSIONS: Among patients who underwent liver transplantation, extubation in the OR compared with extubation in the ICU, significantly reduced the primary composite outcome of 30-day all-cause mortality, in-hospital acute kidney injury (stage 2 or 3), or in-hospital moderate to severe pulmonary complications. TRIAL REGISTRATION: The trial was registered at www.clinicaltrials.gov with registration number NCT04261816. Retrospectively registered on 1st February 2020.

Neuroprotective effects of an engineered commensal bacterium in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine Parkinson disease mouse model via producing glucagon-like peptide-1.

While glucagon-like peptide-1 (GLP-1) was reported to have a positive impact on Parkinson disease, it is extremely short half-life greatly hindered its clinical use. In this study, the mouse strain MG1363-pMG36e-GLP-1 was engineered to continuously express GLP-1 to treat Parkinson disease in a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated Parkinson disease model. In our study, oral supplementation with MG1363-pMG36e-GLP-1 significantly (p < 0.05) reduced MPTP-induced locomotor impairments, increased tyrosine hydroxylase-positive neurons, suppressed microglia and astrocyte activation, and down-regulated expression of several inflammation-related molecules. In addition, MG1363-pMG36e-GLP-1 significantly (p < 0.01) reduced intestinal pathogen Enterobacteriaceae and markedly enhanced the number of probiotic Lactobacillus and Akkermansia. These data suggest that MG1363-pMG36e-GLP-1 could be a novel therapeutic means for Parkinson disease.

A randomized, double-blind, placebo-controlled trial of probiotics to reduce the severity of oral mucositis induced by chemoradiotherapy for patients with nasopharyngeal carcinoma.

BACKGROUND: The objective of this study was to evaluate the effect of a probiotic combination on the severity of oral mucositis (OM), which is a common, unpreventable complication induced by radiochemotherapy in patients with nasopharyngeal carcinoma who undergo concurrent radiochemotherapy (CCRT). METHODS: Eligible patients (n = 99) with locally advanced nasopharyngeal carcinoma who were undergoing CCRT were randomly assigned (2:1) to receive a probiotic combination or placebo during radiochemotherapy, and the incidence of severe OM (grade 3 or higher) was the primary endpoint. RESULTS: Patients taking the probiotic combination showed a significant reduction in the severity of OM. The incidences of grade 0, 1, 2, and 3 OM in the placebo group and the probiotic combination group were 0% and 12.07%, 0% and 55.17%, 54.29% and 17.24%, and 45.71% and 15.52%, respectively. Furthermore, CCRT greatly lowered the number of immune cells, whereas the probiotic combination markedly lowered the reduction rates of CD4+ T cells (76.59% vs 52.85%; P < .05), CD8+ T cells (62.94% vs 29.76%; P < .05), and CD3+ T cells (69.72% vs 45.49%; P < .05) in an A-CCRT-P (after treatment with radiotherapy plus chemotherapy plus the probiotic combination) group. High-throughput sequencing results indicated that CCRT had obviously disturbed the intestinal diversity of patients in an A-CCRT (after treatment with radiotherapy plus chemotherapy plus a placebo) group, whereas the probiotic combination distinctly restored the microbial diversity in the A-CCRT-P group toward that of healthy people and a B-CCRT-P (before the treatment of radiotherapy plus chemotherapy plus the probiotic combination) group. CONCLUSIONS: A probiotic combination significantly enhances the immune response of patients and reduces the severity of OM through modification of gut microbiota.

Inactivation of Rab11a GTPase in Macrophages Facilitates Phagocytosis of Apoptotic Neutrophils.

The timely and efficient clearance of apoptotic neutrophils by macrophages (efferocytosis) is required for the resolution of inflammation and tissue repair, but the regulatory mechanisms remain unclear. In this study, we investigated the role of the small GTPase Ras-related protein in brain (Rab)11a in regulating efferocytosis, and on this basis the resolution of inflammatory lung injury. We observed that apoptotic neutrophil feeding induced a rapid loss of Rab11a activity in bone marrow-derived macrophages and found that depletion of Rab11a in macrophages by small interfering RNA dramatically increased the phagocytosis of apoptotic neutrophils compared with control cells. Additionally, overexpression of wild-type Rab11a inhibited macrophage efferocytosis, whereas overexpression of dominant-negative Rab11a (Rab11a S25N) increased the clearance of apoptotic neutrophils. Rab11a knockdown also increased the surface level of CD36 in macrophages, but it reduced cell surface expression of a disintegrin and metalloproteinase (ADAM) 17. Depletion of ADAM17 rescued the decreased surface CD36 expression found in macrophages overexpressing wild-type Rab11a. Also, blockade of CD36 abolished the augmented efferocytosis seen in Rab11a-depleted macrophages. In mice challenged with endotoxin, intratracheal instillation of Rab11a-depleted macrophages reduced neutrophil count in bronchoalveolar lavage fluid, increased the number of macrophages containing apoptotic neutrophils, and prevented inflammatory lung injury. Thus, Rab11a inactivation in macrophages as a result of apoptotic cell binding initiates phagocytosis of apoptotic neutrophils via the modulation of ADAM17-mediated CD36 cell surface expression. Our results raise the possibility that inhibition of Rab11a activity in macrophages is a promising strategy for activating the resolution of inflammatory lung injury.

Point-of-care ultrasound defines gastric content in elective surgical patients with type 2 diabetes mellitus: a prospective cohort study.

BACKGROUND: Delayed gastric emptying and the resultant "full stomach" is the most important risk factor for perioperative pulmonary aspiration. Using point-of-care gastric sonography, we aimed to investigate the prevalence of full stomach and its risk factors in elective surgical patients with type 2 diabetes. METHODS: Type 2 diabetic and non-diabetic elective surgical patients were included from July 2017 to April 2018 in a 1:1 ratio. The study was retrospectively registered at July 2017, after enrollment of the first participant. Gastric ultrasound was performed 2 h after ingesting clear fluid or 6 h after a light meal. Full stomach was defined by the presence of gastric content in both semi-recumbent and right lateral decubitus positions. For patients with full or intermediate stomach, consecutive ultrasound scan was performed until empty stomach was detected. Logistic regression analyses were used to identify risk factors associated with full stomach. RESULTS: Fifty-two type 2 diabetic and fifty non-diabetic patients were analyzed. The prevalence of full stomach was 48.1% (25/52) in diabetic patients, with 44.0% for 2-h fast after clear fluid and 51.9% for 6-h fast after a light meal, significantly higher than 8% (4/50) in non-diabetic patients (P = 0.000). The average time to empty stomach in diabetic patients was 146.50 ± 40.91 mins for clear liquid and 426.50 ± 45.25 mins for light meal, respectively. Further analysis indicated that presence of diabetes-related eye disease was an independent risk factor of full stomach in diabetic patients (OR = 4.83, P = 0.010). CONCLUSIONS: Almost half of type 2 diabetic patients have a full stomach following the current preoperative fasting guideline. Preoperative ultrasound assessment of gastric content in type 2 diabetic patients is suggested, especially for those with diabetes -related eye disease. TRIAL REGISTRATION: The trial was registered at www.clinicaltrials.gov with registration number NCT03217630 . Retrospectively registered on 14th July 2017.

Preoperative education with image illustrations enhances the effect of tetracaine mucilage in alleviating postoperative catheter-related bladder discomfort: a prospective, randomized, controlled study.

BACKGROUND: Catheter-related bladder discomfort (CRBD), secondary to catheterization of urinary bladder is distressing. The aim of this study was to assess the efficacy of preoperative education on CRBD with image illustration for alleviating CRBD. METHODS: Sixty adult male patients, undergoing elective colonal and rectal surgery, were randomized to receive tetracaine mucilage instilled into the urethra and applied to the catheter (tetracain group), or receive tetracaine mucilage in combination with image illustration on CRBD (image group) before urethral catheterization. The incidence and severity of CRBD were assessed at 0.5, 1, 2, and 6 h after patients' extubation. The severity of postoperative pain, incidence of postoperative agitation and other adverse events were also recorded. RESULTS: Patients in image group reported remarkably less CRBD than those in tetracaine group at 0.5,1, 2 and 6 h after extubation (20, 20, 6.7 and 6.7% v.s. 60, 73.3, 53.3 and 53.3%, respectively, P<0.01). Severe CRBD was not reported in either group. However, the incidence of moderate CRBD was significantly lower in image group, with 6.7% at 1 h and thereafter none occurred, compared to 6.7% at 0.5 h, and increasing to 20% at 1 h, 2 h and 6 h in tetracaine group, respectively. Moreover, patients in image group suffered less moderate to severe postoperative pain than that of tetracaine group (13.3% v.s. 40.0% at 1 h, P = 0.039, 33.3% v.s. 60% at 2 h and 6 h, P = 0.038). CONCLUSIONS: Preoperative education on uretheral catheterization via image illustrations could enhance the effect of tetracaine mucilage in reducing both the incidence and severity of CRBD. TRIAL REGISTRATION: The trial was registered at www,clinicaltrials.gov with registration number NCT03199105 (retrospectively registered). Date of trial registration which is "June 26, 2017".

Vasopressors induce passive pulmonary hypertension by blood redistribution from systemic to pulmonary circulation.

Vasopressors are widely used in resuscitation, ventricular failure, and sepsis, and often induce pulmonary hypertension with undefined mechanisms. We hypothesize that vasopressor-induced pulmonary hypertension is caused by increased pulmonary blood volume and tested this hypothesis in dogs under general anesthesia. In normal hearts (model 1), phenylephrine (2.5 µg/kg/min) transiently increased right but decreased left cardiac output, associated with increased pulmonary blood volume (63% ± 11.8, P = 0.007) and pressures in the left atrium, pulmonary capillary, and pulmonary artery. However, the trans-pulmonary gradient and pulmonary vascular resistance remained stable. These changes were absent after decreasing blood volume or during right cardiac dysfunction to reduce pulmonary blood volume (model 2). During double-ventricle bypass (model 3), phenylephrine (1, 2.5 and 10 µg/kg/min) only slightly induced pulmonary vasoconstriction. Vasopressin (1U and 2U) dose-dependently increased pulmonary artery pressure (52 ± 8.4 and 71 ± 10.3%), but did not cause pulmonary vasoconstriction in normally beating hearts (model 1). Pulmonary artery and left atrial pressures increased during left ventricle dysfunction (model 4), and further increased after phenylephrine injection by 31 ± 5.6 and 43 ± 7.5%, respectively. In conclusion, vasopressors increased blood volume in the lung with minimal pulmonary vasoconstriction. Thus, this pulmonary hypertension is similar to the hemodynamic pattern observed in left heart diseases and is passive, due to redistribution of blood from systemic to pulmonary circulation. Understanding the underlying mechanisms may improve clinical management of patients who are taking vasopressors, especially those with coexisting heart disease.

6-Gingerol protects intestinal barrier from ischemia/reperfusion-induced damage via inhibition of p38 MAPK to NF-κB signalling.

Intestinal ischemia reperfusion (I/R) injury caused by severe trauma, intestinal obstruction, and operation is one of the tough challenges in clinic. 6-Gingerol (6G), a main active ingredient of ginger, is found to have anti-microbial, anti-inflammatory, anti-oxidative, and anti-cancer activities. The present study was designed to characterize the potential protective effects of 6G on rat intestinal I/R injury and reveal the correlated mechanisms. Rat intestinal I/R model was established with clamping the superior mesenteric artery (SMA) and 6G was intragastrically administered for three consecutive days before I/R injury. Caco-2 and IEC-6 cells were incubated under hypoxia/reoxygenation (H/R) conditions to simulate I/R injury in vitro. The results showed that 6G significantly alleviated intestinal injury in I/R injured rats by reducing the generation of oxidative stress and inhibiting p38 MAPK signaling pathway. 6G significantly reduced MDA level and increased the levels of SOD, GSH, and GSH-Px in I/R injured intestinal tissues. 6G significantly decreased the production of proinflammatory cytokines including TNF-α, IL-1ß, and IL-6, and inhibited the expression of inflammatory mediators iNOS/NO in I/R injured intestinal tissues. The impaired intestinal barrier function was restored by using 6G in I/R injured rats and in both Caco-2 and IEC-6 cells characterized by inhibiting p38 MAPK phosphorylation, nuclear translocation of NF-κB, and expression of myosin light chain kinase (MLCK) protein. 6G also reduced the generation of reactive oxygen species (ROS) in both Caco-2 and IEC-6 cells. In vitro transfection of p38 MAPK siRNA mitigated the impact of 6G on NF-κB and MLCK expression, and the results further corroborated the protective effects of 6G on intestinal I/R injury by repressing p38 MAPK signaling. In conclusion, the present study suggests that 6G exerts protective effects against I/R-induced intestinal mucosa injury by inhibiting the formation of ROS and p38 MAPK activation, providing novel insights into the mechanisms of this therapeutic candidate for the treatment of intestinal injury.

Ameliorative effects of atractylodin on intestinal inflammation and co-occurring dysmotility in both constipation and diarrhea prominent rats.

Intestinal disorders often co-occur with inflammation and dysmotility. However, drugs which simultaneously improve intestinal inflammation and co-occurring dysmotility are rarely reported. Atractylodin, a widely used herbal medicine, is used to treat digestive disorders. The present study was designed to characterize the effects of atractylodin on amelioration of both jejunal inflammation and the co-occurring dysmotility in both constipation-prominent (CP) and diarrhea-prominent (DP) rats. The results indicated that atractylodin reduced proinflammatory cytokines TNF-α, IL-1ß, and IL-6 in the plasma and inhibited the expression of inflammatory mediators iNOS and NF-kappa B in jejunal segments in both CP and DP rats. The results indicated that atractylodin exerted stimulatory effects and inhibitory effects on the contractility of jejunal segments isolated from CP and DP rats respectively, showing a contractile-state-dependent regulation. Atractylodin-induced contractile-state-dependent regulation was also observed by using rat jejunal segments in low and high contractile states respectively (5 pairs of low/high contractile states). Atractylodin up-regulated the decreased phosphorylation of 20 kDa myosin light chain, protein contents of myosin light chain kinase (MLCK), and MLCK mRNA expression in jejunal segments of CP rats and down-regulated those increased parameters in DP rats. Taken together, atractylodin alleviated rat jejunal inflammation and exerted contractile-state-dependent regulation on the contractility of jejunal segments isolated from CP and DP rats respectively, suggesting the potential clinical implication for ameliorating intestinal inflammation and co-occurring dysmotility.

Evaluation of the Antioxidative, Antibacterial, and Anti-Inflammatory Effects of the Aloe Fermentation Supernatant Containing Lactobacillus plantarum HM218749.1.

Little work is done to develop Aloe vera (AV) using probiotics. To explore the potential benefits, the antioxidant effects and the antibacterial effects on foodborne pathogens of Aloe fermentation supernatant were evaluated in vitro. Our results indicated that the Aloe fermentation supernatant fermented by Lactobacillus plantarum HM218749.1 had very strong scavenging capacities of the DPPH (86%), O2 (•-) (85%), (•)OH (76%), and Fe(2+) chelation (82%) and reducing powers (242.5 mg/L), and the inhibition zones for Salmonella typhimurium, Salmonella enteritidis, Shigella flexneri, Escherichia coli, Listeria monocytogenes, S. dysenteriae 301, Staphylococcus aureus Cowan1, and Propionibacterium acnes were 16, 15, 19, 20, 21, 20, and 27 mm. Moreover, the low concentration of Aloe fermentation supernatant had significantly reduced the production of IL-1ß, TNF-α, and IL-6 in both mRNA and protein levels (P < 0.01). Therefore, the Aloe fermentation supernatant can be used as functional beverage or cosmetic ingredients to guard human intestinal health, delaying senescence, and prevent chronic diseases.