Fe(III)/peroxymonosulfate oxidation system for the degradation of rhein, a toxic component abundance in rhubarb residue.

Rhubarb is widely used in health care, but causing a great amount of rhein-containing herbal residue. Rhein with several toxicities might pollute environment, damage ecology and even hazard human health if left untreated. In this study, the degradation effects of bisulfite- (BS) and peroxymonosulfate- (PMS) based oxidation systems on rhein in rhubarb residue were compared and investigated. The effects of BS and PMS with two valence states of ferric ion (Fe) on the degradation of rhein in rhubarb residue were optimized for the selection of optimal oxidation system. The influences of reaction temperature, reaction time and initial pH on the removal of rhein under the optimal oxidation system were evaluated. The chemical profiles of rhubarb residue with and without oxidation process were compared by UPLC-QTOF-MS/MS, and the degradation effects were investigated by PLS-DA and S plot/OPLS-DA analysis. The results manifested that PMS showed relative higher efficiency than BS on the degradation of rhein. Moreover, Fe(III) promoted the degradation effect of PMS, demonstrated that Fe(III)/PMS is the optimal oxidation system to degrade rhein in rhubarb residue. Further studies indicated that the degradation of rhein by the Fe(III)/PMS oxidation system was accelerated with the prolong of reaction time and the elevation of reaction temperature, and also affected by the initial pH. More importantly, Fe(III)/PMS oxidation system could degrade rhein in rhubarb residue completely under the optimal conditions. In conclusion, Fe(III)/PMS oxidation system is a feasible method to treat rhein in rhubarb residue.

Delirium in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: a multicentre randomised trial.

BACKGROUND: Delirium is a common and disturbing postoperative complication that might be ameliorated by propofol-based anaesthesia. We therefore tested the primary hypothesis that there is less delirium after propofol-based than after sevoflurane-based anaesthesia within 7 days of major cancer surgery. METHODS: This multicentre randomised trial was conducted in 14 tertiary care hospitals in China. Patients aged 65-90 yr undergoing major cancer surgery were randomised to either propofol-based anaesthesia or to sevoflurane-based anaesthesia. The primary endpoint was the incidence of delirium within 7 postoperative days. RESULTS: A total of 1228 subjects were enrolled and randomised, with 1195 subjects included in the modified intention-to-treat analysis (mean age 71 yr; 422 [35%] women); one subject died before delirium assessment. Delirium occurred in 8.4% (50/597) of subjects given propofol-based anaesthesia vs 12.4% (74/597) of subjects given sevoflurane-based anaesthesia (relative risk 0.68 [95% confidence interval {CI}: 0.48-0.95]; P=0.023; adjusted relative risk 0.59 [95% CI: 0.39-0.90]; P=0.014). Delirium reduction mainly occurred on the first day after surgery, with a prevalence of 5.4% (32/597) with propofol anaesthesia vs 10.7% (64/597) with sevoflurane anaesthesia (relative risk 0.50 [95% CI: 0.33-0.75]; P=0.001). Secondary endpoints, including ICU admission, postoperative duration of hospitalisation, major complications within 30 days, cognitive function at 30 days and 3 yr, and safety outcomes, did not differ significantly between groups. CONCLUSIONS: Delirium was a third less common after propofol than sevoflurane anaesthesia in older patients having major cancer surgery. Clinicians might therefore reasonably select propofol-based anaesthesia in patients at high risk of postoperative delirium. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IPR-15006209) and ClinicalTrials.gov (NCT02662257).

Long-term survival in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: follow-up of a multicentre randomised trial.

BACKGROUND: Experimental evidence indicates that i.v. anaesthesia might reduce cancer recurrence compared with volatile anaesthesia, but clinical information is observational only. We therefore tested the primary hypothesis that propofol-based anaesthesia improves survival over 3 or more years after potentially curative major cancer surgery. METHODS: This was a long-term follow-up of a multicentre randomised trial in 14 tertiary hospitals in China. We enrolled 1228 patients aged 65-90 yr who were scheduled for major cancer surgery. They were randomised to either propofol-based i.v. anaesthesia or to sevoflurane-based inhalational anaesthesia. The primary endpoint was overall survival after surgery. Secondary endpoints included recurrence-free and event-free survival. RESULTS: Amongst subjects randomised, 1195 (mean age 72 yr; 773 [65%] male) were included in the modified intention-to-treat analysis. At the end of follow-up (median 43 months), there were 188 deaths amongst 598 patients (31%) assigned to propofol-based anaesthesia compared with 175 deaths amongst 597 patients (29%) assigned to sevoflurane-based anaesthesia; adjusted hazard ratio 1.02; 95% confidence interval (CI): 0.83-1.26; P=0.834. Recurrence-free survival was 223/598 (37%) in patients given propofol anaesthesia vs 206/597 (35%) given sevoflurane anaesthesia; adjusted hazard ratio 1.07; 95% CI: 0.89-1.30; P=0.465. Event-free survival was 294/598 (49%) in patients given propofol anaesthesia vs 274/597 (46%) given sevoflurane anaesthesia; adjusted hazard ratio 1.09; 95% CI 0.93 to 1.29; P=0.298. CONCLUSIONS: Long-term survival after major cancer surgery was similar with i.v. and volatile anaesthesia. Propofol-based iv. anaesthesia should not be used for cancer surgery with the expectation that it will improve overall or cancer-specific survival. CLINICAL TRIAL REGISTRATIONS: ChiCTR-IPR-15006209; NCT02660411.

Necrostatin-1 attenuates Caspase-1-dependent pyroptosis induced by the RIPK1/ZBP1 pathway in ventilator-induced lung injury.

BACKGROUND: Ventilator-induced lung injury (VILI) is a complex pathophysiological process leading to acute respiratory distress syndrome (ARDS) and poor outcomes in affected patients. As a form of programmed cell death, pyroptosis is proposed to play an important role in the development of ARDS. Here we investigated whether treating mice with the specific RIPK1 inhibitor Necrostatin-1 (Nec-1) before mechanical ventilation could inhibit pyroptosis and alleviate lung injury in a mouse model. METHODOLOGYS: Anesthetized C57BL/6J mice received a transtracheal injection of Nec-1 (5 mg/kg) or vehicle (DMSO) 30 min before the experiment which was ventilated for up to 4 h. Lung damage was assessed macroscopically and histologically with oedema measured as the wet/dry ratio of lung tissues. The release of inflammatory mediators into bronchoalveolar lavage fluid (BALF) was assessed by ELISA measurements of TNF-α,interleukin-1ß (IL-1ß), and IL-6. The expression of RIPK1, ZBP1, caspase-1, and activated (cleaved) caspase-1 were analyzed using western blot and immunohistochemistry, and the levels of gasdermin-D (GSDMD) and IL-1ß were analyzed by immunofluorescence staining. RESULTS: High tidal ventilation produced time-dependent inflammation and lung injury in mice which could be significantly reduced by pretreatment with Nec-1. Notably, Nec-1 reduced the expression of key pyroptosis mediator proteins in lung tissues exposed to mechanical ventilation, including caspase-1, cleaved caspase-1, and GSDMD together with inhibiting the release of inflammatory cytokines. CONCLUSION: Nec-1 pretreatment alleviates pulmonary inflammatory responses and protects the lung from mechanical ventilation damage. The beneficial effects were mediated at least in part by inhibiting caspase-1-dependent pyroptosis through the RIPK1/ZBP1 pathway.

Subclassification of patients with solitary hepatocellular carcinoma based on post-hepatectomy survival: a large retrospective study.

Official guidelines group together all cases of solitary hepatocellular carcinoma (HCC) without macroscopic vascular invasion, regardless of tumor size. Here, we examined whether this is justified based on overall survival (OS) after hepatic resection (HR). Patients with newly diagnosed solitary HCC treated by initial HR from January 2004 to October 2013 were classified into six groups based on tumor size (in 2-cm increments). Combining adjacent categories with similar OS led to three groups: ≤5 cm (n = 426), >5 and ≤8 cm (n = 229), and >8 cm (n = 202). Among all patients, median survival time was 62 months, and OS was 95 % at 1 year, 73 % at 3 years, and 54 % at 5 years. Patients in the ≤5 cm group showed significantly higher OS (P < 0.001) and lower tumor recurrence (P = 0.004) than those in the >5 and ≤8 cm group, who in turn showed significantly higher OS (P = 0.003) and lower tumor recurrence (P = 0.021) than those in the >8 cm group. Our results suggest that patients with solitary HCC should be subclassified based on tumor size for more accurate prognosis. We propose defining solitary HCC tumors >5 and ≤8 cm as "large" and tumors >8 cm as "huge".

Efficacy of triclosan-coated sutures for reducing risk of surgical site infection in adults: a meta-analysis of randomized clinical trials.

BACKGROUND: Surgical site infection (SSI) is the third most frequent type of nosocomial infections. Triclosan-coated sutures are often used to reduce the risk of SSI, but studies examining this have given conflicting results. Therefore, this meta-analysis was performed to assess the efficacy of triclosan-coated sutures for reducing risk of SSI in adults. METHODS: PubMed, EMBASE, Google Scholar, and ClinicalTrials.gov were searched to identify randomized clinical trials evaluating triclosan-coated sutures for preventing SSI on patients 18 y or older. RESULTS: Thirteen randomized clinical trials involving 5256 participants were included. Triclosan-coated sutures were associated with lower risk of SSI than uncoated sutures across all surgeries (risk ratio [RR] 0.76, 95% confidence interval [CI] 0.65-0.88, P < 0.001). Similar proportions of patients experienced wound dehiscence with either type of suture (RR 0.97, 95% CI 0.49-1.89, P = 0.92). Subgroup analysis showed lower risk of SSI with triclosan-coated sutures in abdominal surgeries (RR 0.70, 95% CI 0.50-0.99, P = 0.04) and group with prophylactic antibiotic (RR 0.79, 95% CI 0.63-0.99, P = 0.04). However, such risk reduction was not observed in cardiac surgeries, breast surgeries, or group without prophylactic antibiotic. CONCLUSIONS: Triclosan-coated sutures can decrease the incidence of SSI in abdominal surgeries and might not interfere with wound healing process. Nevertheless, further studies are needed to examine whether triclosan-coated sutures are effective at preventing SSI in non-abdominal surgeries and to further study the interaction of antibiotic prophylaxis with triclosan-coated sutures.

Zoledronate for metastatic bone disease and pain: a meta-analysis of randomized clinical trials.

BACKGROUND: Randomized controlled trials (RCTs) have reported different results when using zoledronate to treat skeletal-related events (SREs) and bone pain in patients with metastatic bone disease (MBD), and few have looked at the risks and benefits of long-term use of the drug. This meta-analysis aimed to investigate the efficacy and safety of zoledronate to treat MBD in the short and long-term. METHODS: PubMed, EMBASE, and the Cochrane Library were searched to identify RCTs evaluating zoledronate for MBD. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated. RESULTS: Twelve RCTs involving 4,450 patients were included in the meta-analysis. Zoledronate decreased the risk of developing SREs compared with placebo (RR 0.75, 95% CI 0.69 to 0.81, P < 0.001). Zoledronate consistently reduced the brief pain inventory (BPI) below baseline compared with placebo at 3, 12, and 24 months. In addition, the likelihood of experiencing a bone pain event was significantly lower in the zoledronate group than in the placebo group (RR 0.83, 95% CI 0.76 to 0.89, P < 0.001). While the two groups did not differ significantly in the incidence of nausea(RR = 1.07, 95% CI 0.96 to 1.19, P = 0.250), emesis (RR 0.94, 95% CI 0.81 to 1.09, P = 0.420), or adverse renal events (RR 1.41, 95% CI 0.94 to 2.11, P = 0.09), the zoledronate group showed a significantly higher relative risk of pyrexia (RR 1.43, 95% CI 1.20 to 1.70, P < 0.001), fatigue (RR 1.26, 95% CI 1.10 to 1.43, P < 0.001), and anemia (RR 1.33, 95% CI 1.14 to 1.55, P < 0.001). CONCLUSION: Compared to placebo, zoledronate significantly reduced the incidence of bone pain and SREs in patients with MBD for periods as long as 24 months. In addition, zoledronate is generally well tolerated over this long period.

Transforming growth factor-ß1 attenuates inflammation and lung injury with regulating immune function in ventilator-induced lung injury mice.

Ventilator-induced lung injury (VILI) is a lung injury induced or aggravated by mechanical ventilation. Transforming growth factor (TGF)-ß1 is a cytokine that mediates immune function, enabling inflammatory attenuation and tissue repair. Here, we hypothesized that it plays an important role in the attenuation of VILI and inflammation. Ventilation with high tidal volume was performed on C57BL/6 mice to establish a VILI model. After 4 h of ventilation, mice were sacrificed (end of ventilation [EOV]) or extubated for resuscitation at 4 h (post-ventilation 4 h [PV4h]), 8 h (PV8h) and 24 h post-ventilation (PV1d). Recombinant mouse TGF-ß1 (rTGF-ß1) and the neutralization antibody of TGF-ß1 (nTAb) were used in vivo to examine the effect of TGF-ß1 on immune function and inflammatory attenuation in VILI mice. Lung injury was exacerbated at the same trend as the interleukin (IL)-1ß level, peaking at PV1d, whereas IL-6 and tumor necrosis factor (TNF)-α levels gradually reduced. Most active phagosomes, swollen round mitochondria, and cavitating lamellar bodies were observed at PV4h. The CD4+ T cells were significantly increased from PV4h to PV1d, and the CD8a + T cells were higher in the PV4h and PV1d groups; furthermore, the mice in the PV8h group showed highest proportion of CD4+CD8a+ T cells and CD4+/CD8a+ ratio. CD19 + and CD5 + CD19 + B cells in VILI mice began to increase at PV1d. The pulmonary expression of latent and monomer TGF-ß1 increased at PV4h and PV8h. Treatment of rTGF-ß1 only induced high expression of latent and monomer TGF-ß1 at EOV to decrease pulmonary levels of IL-1ß, IL-6, and TNF-α; however, lung injury attenuated from EOV to PV1d. TGF-ß1 induced the delayed elevation of CD4+/CD8a+ T cells ratio and activation of pulmonary CD4+CD8a+ double-positive T cells under certain conditions. Elastic fibers and celluloses, although relatively less proteoglycan, were observed with the overexpression of TGF-ß1 at PV4h and PV8h. In conclusion, TGF-ß1 attenuates the inflammatory response and lung injury of VILI via immune function regulation.

Primer exchange reaction-amplified protein-nucleic acid interactions for ultrasensitive and specific microRNA detection.

Protein-nucleic acid interactions are not only fundamental to genetic regulation and cellular metabolism, but molecular basis to artificial biosensors. However, such interactions are generally weak and dynamic, making their specific and sensitive quantitative detection challenging. By using primer exchange reaction (PER)-amplified protein-nucleic acid interactions, we here design a universal and ultrasensitive electrochemical sensor to quantify microRNAs (miRNAs) in blood. This PER-miR sensor leverages specific recognition between S9.6 antibodies and miRNA/DNA hybrids to couple with PER-derived multi-enzyme catalysis for ultrasensitive miRNA detection. Surface binding kinetic analysis shows a rational Kd (8.9 nM) between the miRNA/DNA heteroduplex and electrode-attached S9.6 antibody. Based on such a favorable affinity, the programmable PER amplification enables the sensor to detect target miRNAs with sensitivity up to 90.5 aM, three orders of magnitude higher than that without PER in routine design, and with specificity of single-base resolution. Furthermore, the PER-miR sensor allows detecting multiple miRNAs in parallel, measuring target miRNA in lysates across four types of cell lines, and differentiating tumor patients from healthy individuals by directly analyzing the human blood samples (n = 40). These advantages make the sensor a promising tool to enable quantitative sensing of biomolecular interactions and precision diagnostics.

A resorufin-based fluorescence probe for visualizing biogenic amines in cells and zebrafish.

Biogenic amines (BAs) are a family of nitrogen-bearing natural organic molecules with at least one primary amine, which play an important role in living organisms. Elevated concentration of BAs may cause neuron disorder, Parkinson's disease and many other diseases. Therefore, it is essential to monitor BAs in living organisms. Herein, we reported a resorufin-based fluorescence probe for sensing of various BAs. Upon nucleophilic substitution reaction with BAs, the probe released resorufin, affording to strong fluorescence emission at 592 nm with rapid response (<8 min), good selectivity and a low detection limit (LOD = 0.47 µM). The probe has low cytotoxicity and good membrane permeability, and has been successfully used to visualize BAs in living cells and zebrafish with good performance.

The Effectiveness and Safety of General and Spinal Anesthesia on Systemic Inflammatory Response in Patients with Tumor-Type Total Knee Arthroplasty.

BACKGROUND: The anesthesia procedure in tumor-type total knee arthroplasty (TKA) may contribute to systemic inflammatory response. Therefore, we aim to investigate the effectiveness and safety of general and spinal anesthesia in patients with tumor-type TKA. PATIENTS AND METHODS: Twenty-five patients with tumors around the knee undergoing primary unilateral TKA were randomly divided into the general anesthesia group (n = 13) and spinal anesthesia group (n = 12). Knee joint HSS scores and Western Ontario and McMaster University osteoarthritis index (WOMAC osteoarthritis) were recorded before surgery and 12 months after surgery. Visual analogue scale, C-reactive protein (CPR), tumor necrosis factor-α (TNF-α), and interleukin-8 (IL-8) concentration were measured preoperatively (T0), on the day of the operation (T1), and on the first day (T2) after the operation. Complications in the two groups were recorded. RESULTS: The operative time, intraoperative blood loss, postoperative drainage, tourniquet time, and complication rate were not significantly different between the general anesthesia and spinal anesthesia groups (all p > 0.05). There were no significant differences in CPR (7.6 ± 3.1, 8.1 ± 4.1, 91.3 ± 24.2 vs. 7.1 ± 2.9, 7.6 ± 3.8, 85.1 ± 19.3 pg/mL, respectively), IL-8 (12.2 ± 6.6, 13.4 ± 7.3, 19.2 ± 10.5 vs. 11.9 ± 5.7, 12.9 ± 8.6, 22.2 ± 12.4 pg/mL, respectively), and TNF-α (2.5 ± 1.7, 2.2 ± 1.9, 2.8 ± 2.1 vs. 2.4 ± 1.3, 2.7 ± 2.1, 2.9 ± 1.6 pg/mL, respectively) between the two groups at T0, T1, and T2 (all p > 0.05). There were no statistical differences in pre- and postoperative HSS knee scores (39.78 ± 11.3, 90.24 ± 15.3 vs. 42.68 ± 12.5, 91.21 ± 16.3) and WOMAC indexes (49.89 ± 7.9, 25.12 ± 6.2 vs. 51.3 ± 8.3, 23.15 ± 5.3) between the two groups (p > 0.05). CONCLUSION: General anesthesia and spinal anesthesia in patients with tumor-type TKA had the same effectiveness and safety.

Transversus Abdominis Plane Block versus Wound Infiltration with Conventional Local Anesthetics in Adult Patients Underwent Surgery: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: How to effectively control the postoperative pain of patients is extremely important to clinicians. Transversus abdominis plane (TAP) block is a novel analgesic method reported to greatly decrease postoperative pain. However, in many areas, there still exists a phenomenon of surgeons using wound infiltration (WI) with conventional local anesthetics (not liposome anesthetics) as the main means to decrease postoperative pain because of traditional wisdom or convenience. Here, we compared the analgesic effectiveness of the two different methods to determine which method is more suitable for adult patients. Materials and methods. A systematic review and meta-analysis of randomized controlled trials (RCTs) comparing TAP block and WI without liposome anesthetics in adult patients were performed. Frequently used databases were extensively searched. The main outcomes were postoperative pain scores in different situations (at rest or during movement) and the time until the first use of rescue analgesics. The secondary outcomes were postoperative nausea and vomiting (PONV) incidence and patient satisfaction scores. RESULTS: Fifteen studies with 983 participants met the inclusion criteria and were included in the present study. The heterogeneity in the final analysis regarding the pain score was low to moderate. The major results of the sensitivity analysis were stable. WI had the same analgesic effect as TAP block only at the one-hour postoperative time point (mean difference = -0.32, 95% confidence interval (-0.87, 0.24), P = 0.26) and was associated with a shorter time until the first rescue analgesic and poorer patient satisfaction. CONCLUSION: TAP block results in a more effective and steady analgesic effect than WI with conventional local anesthetics in adult patients from the early postoperative period and obtains higher patient satisfaction.

Clinical impact of type 2 diabetes mellitus on outcomes after one-lung ventilation during thoracic surgery: a retrospective cohort study.

BACKGROUND: The preoperative presence of diabetes mellitus (DM) has been recently demonstrated to be a risk factor for adverse events after thoracic surgery. However, the specific effects of presence of DM preoperatively on thoracic surgery is not known. This study aimed to investigate the association between preoperative DM and clinical outcomes and the short-term survival rates after thoracic surgery. METHODS: In this retrospective, observational, and matched-pair analysis study, patients receiving thoracic surgery from a tertiary university hospital in 2 consecutive years were grouped as either type 2 DM (T2DM) or controlled within the first 24 hours after surgery. Multivariate Cox regression was conducted to investigate the impact of T2DM within the first 24 hours of admission on in-intensive care unit (ICU) and hospital survival. RESULTS: Among the included thoracic patients, 41 (8.4%) had T2DM and 450 (91.6%) did not have T2DM. In the single-factor analyses, T2DM patients were shown to have a higher preoperative white blood cells (WBCs) count, increased release of immunoglobulin A, complement C3 and C4, impaired kidney function with high level of urea, and low expression of alanine aminotransferase (ALT) and monoamine oxidase (MAO). In multivariate analyses, the preoperative urea level was associated with a low-grade risk of dying for the ICU survival time. In contrast, preoperative complement C3 level favored a positive contribution in-ICU survival. Besides the complement C3 level, immunoglobulin A level remained a positive contribution in regression models of hospital survival. CONCLUSIONS: Pre-admission T2DM was not associated with an increased in-ICU and hospital mortality among patients with thoracic surgery. Furthermore, they were accompanied by impaired kidney function, activated inflammation and liver function.

Effects of erector spinae plane block on postoperative pain and side-effects in adult patients underwent surgery: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Recently, the effects of erector spinae plane block on postoperative pain have become increasingly controversial. This meta-analysis compared the effects of ESP block versus placebo on postoperative analgesia and side effects to determine whether the new technique is a reliable alternative for pain management. METHODS: PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang Database were searched for clinical studies investigating the analgesic effect of ESP block versus placebo. The primary outcomes included the visual analogue scale (VAS) at rest and during movement, as well as the postoperative morphine consumption in 24 h, and the secondary outcome was the rate of postoperative nausea and vomiting (PONV). The choice of using the fixed or random-effects model depended on whether the heterogeneity tested by I2 statistic was more than 50%. Seeking sources of heterogeneity and exploring the effect of clinical details on the final result were performed by subgroup analysis. Additionally, the test for stability of the pooled result was realized by sensitivity analysis. Finally, we evaluated the quality of the evidence for the outcomes. STATA 13.0 software was selected as the main analysis software in the meta-analysis. RESULTS: Eighteen randomized controlled trials (RCTs) comprising 1041 patients were reviewed. This meta-analysis showed that ESP block could significantly reduce patients' pain scores at 1 h, 6 h, 12 h, and 24 h after surgery at rest or during movement; 24-h postoperative morphine consumption; and the incidence of PONV. CONCLUSIONS: ESP block as a novel technique exhibited superior postoperative analgesic effects, reducing the postoperative complications in spinal, thoracic, and abdominal surgeries during the early postoperative period. However, as a new nerve block technique, numerous large-sized RCTs are needed for further research.

Mitophagy-Mediated mtDNA Release Aggravates Stretching-Induced Inflammation and Lung Epithelial Cell Injury via the TLR9/MyD88/NF-κB Pathway.

BACKGROUND: In animal models of ventilation-induced lung injury, mitophagy triggers mitochondria damage and the release of mitochondrial (mt) DNA, which activates inflammation. However, the mechanism of this process is unclear. METHODS: A model of cyclic stretching (CS)-induced lung epithelial cell injury was established. The genetic intervention of phosphatase and tensin homolog-induced kinase 1 (PINK1) expression via lentivirus transfection was used to identify the relationship between PINK1-mediated mitophagy and mtDNA release in stretching-induced inflammatory response and injury. Pharmacological inhabitation of Toll-like receptor 9 (TLR9) and myeloid differentiation factor 88 (MyD88) expression was performed via their related inhibitors, while pre-treatment of exogenous mtDNA was used to verify the role of mtDNA in stretching-induced inflammatory response and injury. RESULTS: Using a cell culture model of CS, we found that knocking down PINK1 in lung epithelial cells reduced mitophagy activation and mtDNA release, leading to milder inflammatory response and injury; conversely, up-regulating PINK1 exacerbated stretching-induced inflammation and injury, and similar effects were observed by upregulating TLR9 to induce expression of MyD88 and nuclear factor-κB (NF-κB)/p65. Down-regulating MyD88 protected lung epithelial cells from stretching injury and decreased NF-κB/p65 expression. CONCLUSION: These findings suggest that PINK1-dependent mitophagy and associated TLR9 activation is indeed a major factor in stretch-induced cell injury via a mechanism in which released mtDNA activates TLR9 and thereby the MyD88/NF-κB pathway. Inhibiting this process may be a therapeutic approach to prevent inflammation and cell injury in patients on mechanical ventilation.

Inhibition of p38 MAPK Mitigates Lung Ischemia Reperfusion Injury by Reducing Blood-Air Barrier Hyperpermeability.

Background: Lung ischemia reperfusion injury (LIRI) is a complex pathophysiological process activated by lung transplantation and acute lung injury. The p38 mitogen-activated protein kinase (MAPK) is involved in breakdown of the endothelial barrier during LIRI, but the mechanism is still unclear. Therefore, we investigated the function of p38 MAPK in LIRI in vivo and in vitro. Methods: Sprague-Dawley rats were subjected to ischemia reperfusion with or without pretreatment with a p38 MAPK inhibitor. Lung injury was assessed using hematoxylin and eosin staining, and pulmonary blood-air barrier permeability was evaluated using Evans blue staining. A rat pulmonary microvascular endothelial cell line was infected with lentiviral expressing short hairpin (sh)RNA targeting p38 MAPK and then cells were subjected to oxygen/glucose deprivation and reoxygenation (OGD/R). Markers of endothelial destruction were measured by western blot and immunofluorescence. Results: In vivo LIRI models showed structural changes indicative of lung injury and hyperpermeability of the blood-air barrier. Inhibiting p38 MAPK mitigated these effects. Oxygen/glucose deprivation and reoxygenation promoted hyperpermeability of the endothelial barrier in vitro, but knockdown of p38 MAPK attenuated cell injury; maintained endothelial barrier integrity; and partially reversed injury-induced downregulation of permeability protein AQP1, endothelial protective protein eNOS, and junction proteins ZO-1 and VE-cadherin while downregulating ICAM-1, a protein involved in destroying the endothelial barrier, and ET-1, a protein involved in endothelial dysfunction. Conclusion: Inhibition of p38 MAPK alleviates LIRI by decreasing blood-air hyperpermeability. Blocking p38 MAPK may be an effective treatment against acute lung injury.

Necroptosis in pulmonary macrophages mediates lipopolysaccharide-induced lung inflammatory injury by activating ZBP-1.

Z-DNA combined protein-1 (ZBP-1), an important necroptosis regulator, activates necrosis-associated inflammation and immune response. Increased ZBP-1 expression in necroptosis-associated inflammation correlates with activation of receptor interacting protein kinase (RIPK1)/RIPK3 and nuclear factor (NF)-κB. Here we explored the role of ZBP-1-mediated necroptosis in lipopolysaccharide (LPS)-induced lung injury. Bone marrow-derived macrophages (BMDMs) transfected with a small interfering RNA against ZBP-1 or scrambled control RNA were administered to mice that had been depleted of alveolar macrophages (AMs). Then the animals were treated with E. coli LPS (2.0 mg/kg) or phosphate-buffered saline by intratracheal instillation for 48 h. LPS-induced lung inflammatory injury was verified, and the mRNA and protein expression of ZBP-1, RIPK1/RIPK3 and NF-κB in AMs were then assessed by Western blot and real time-quantitative polymerase chain reaction. In mechanistic studies in vitro, BMDM cultures were treated with different concentrations of LPS for 24 h, and the expression of ZBP-1, RIPK1/RIPK3 and NF-κB were assessed. LPS activated ZBP-1-mediated necroptosis, primarily in AMs. This activation and associated lung inflammatory injury were much weaker after AMs depletion or silencing of ZBP-1 in BMDMs, which correlated with down-regulation of RIPK1/RIPK3. These in vivo findings were confirmed in experiments with cultures of BMDMs. In conclusion, LPS induces lung inflammation and injury by activating ZBP-1-mediated necroptosis and release of pro-inflammatory cytokines by macrophages.

Non-intubated anesthesia in patients undergoing video-assisted thoracoscopic surgery: A systematic review and meta-analysis.

INTRODUCTION: Non-intubated anesthesia (NIA) has been proposed for video-assisted thoracoscopic surgery (VATS), although how the benefit-to-risk of NIA compares to that of intubated general anesthesia (IGA) for certain types of patients remains unclear. Therefore, the aim of the present meta-analysis was to understand whether NIA or IGA may be more beneficial for patients undergoing VATS. METHODS: A systematic search of Cochrane Library, Pubmed and Embase databases from 1968 to April 2019 was performed using predefined criteria. Studies comparing the effects of NIA or IGA for adult VATS patients were considered. The primary outcome measure was hospital stay. Pooled data were meta-analyzed using a random-effects model to determine the standard mean difference (SMD) with 95% confidence intervals (CI). RESULTS AND DISCUSSION: Twenty-eight studies with 2929 patients were included. The median age of participants was 56.8 years (range 21.9-76.4) and 1802 (61.5%) were male. Compared to IGA, NIA was associated with shorter hospital stay (SMD -0.57 days, 95%CI -0.78 to -0.36), lower estimated cost for hospitalization (SMD -2.83 US, 95% CI -4.33 to -1.34), shorter chest tube duration (SMD -0.32 days, 95% CI -0.47 to -0.17), and shorter postoperative fasting time (SMD, -2.76 days; 95% CI -2.98 to -2.54). NIA patients showed higher levels of total lymphocytes and natural killer cells and higher T helper/T suppressor cell ratio, but lower levels of interleukin (IL)-6, IL-8 and C-reactive protein (CRP). Moreover, NIA patients showed lower levels of fibrinogen, cortisol, procalcitonin and epinephrine. CONCLUSIONS: NIA enhances the recovery from VATS through attenuation of stress and inflammatory responses and stimulation of cellular immune function.

Conscious Sedation versus General Anesthesia for Patients with Acute Ischemic Stroke Undergoing Endovascular Therapy: A Systematic Review and Meta-Analysis.

The aim of this study is to compare the effect of conscious sedation (CS) with general anesthesia (GA) on clinical outcomes in patients with acute ischemic stroke (AIS) undergoing endovascular therapy (EVT). MEDLINE, EMBASE, and Cochrane Central Registers of Controlled Trials (from inception to July 2017) were searched for reports on CS and GA of AIS undergoing EVT. Two reviewers assessed the eligibility of the identified studies and extracted data. Data were analyzed using the fixed-effects model, and the sources of heterogeneity were explored by sensitive analysis. Trial sequential analysis was conducted to monitor boundaries for the limitation of global type I error, and GRADE system was demonstrated to evaluate the quality of evidence. A total of thirteen studies were finally identified. Pooled analysis of the incidence of mRS score ≦ 2 after hospital discharge and one or three months in the CS group was higher than that in the GA group. The all-causing mortality of AIS patients in the CS group was lower than that in the GA group. There were no differences in the proportion of IA rtPA and thrombolysis between the two groups. Compared with AIS patients receiving GA, the all-causing mortality in the AIS patients receiving CS was decreased, while incidence of mRS score ≦ 2 at hospital discharge and one or three months was increased.