Papillary vitreous detachment as a possible accomplice in non-arteritic anterior ischaemic optic neuropathy.

AIM: To evaluate the role of papillary vitreous detachment in the pathogenesis of non-arteritic anterior ischaemic optic neuropathy (NAION) by comparing the features of vitreopapillary interface between NAION patients and normal individuals. METHODS: This study included 22 acute NAION patients (25 eyes), 21 non-acute NAION patients (23 eyes) and 23 normal individuals (34 eyes). All study participants underwent swept-source optical coherence tomography to assess the vitreopapillary interface, peripapillary wrinkles and peripapillary superficial vessel protrusion. The statistical correlations between peripapillary superficial vessel protrusion measurements and NAION were analysed. Two NAION patients underwent standard pars plana vitrectomy. RESULTS: Incomplete papillary vitreous detachment was noted in all acute NAION patients. The prevalence of peripapillary wrinkles was 68% (17/25), 30% (7/23) and 0% (0/34), and the prevalence of peripapillary superficial vessel protrusion was 44% (11/25), 91% (21/23) and 0% (0/34) in the acute, non-acute NAION and control groups, respectively. The prevalence of peripapillary superficial vessel protrusion was 88.9% in the eyes without retinal nerve fibre layer thinning. Furthermore, the number of peripapillary superficial vessel protrusions in the superior quadrant was significantly higher than that in the other quadrants in eyes with NAION, consistent with the more damaged visual field defect regions. Peripapillary wrinkles and visual field defects in two patients with NAION were significantly attenuated within 1 week and 1 month after the release of vitreous connections, respectively. CONCLUSION: Peripapillary wrinkles and superficial vessel protrusion may be signs of papillary vitreous detachment-related traction in NAION. Papillary vitreous detachment may play an important role in NAION pathogenesis.

[Predictive value of postoperative serum procalcitonin concentration for moderate to severe acute respiratory distress syndrome in patients undergoing cardiopulmonary bypass surgery].

OBJECTIVE: To explore the changes of serum procalcitonin (PCT) level in patients with moderate and severe acute respiratory distress syndrome (ARDS) after cardiac surgery under cardiopulmonary bypass (CPB), and try to find out the best cut-off of PCT to predict the progression to moderate and severe ARDS. METHODS: Medical records of patients undergoing cardiac surgery with CPB in Fujian Provincial Hospital from January 2017 to December 2019 were retrospectively analyzed. Adult patients who were admitted in intensive care unit (ICU) for more than 1 day and had PCT values on the first postoperative day were enrolled. Clinical data such as patient demographics, past history, diagnosis, and New York Heart Association (HYHA) classification, and the operation mode, procedure duration, CPB duration, aortic clamp duration, intraoperative fluid balance, calculation of 24 hours postoperative fluid balance and vasoactive-inotropic score (VIS); 24 hours postoperative C-reactive protein (CRP), N-terminal B-type natriuretic peptide precursor (NT-proBNP) and PCT levels were collected. Two clinicians independently made the diagnosis of ARDS according to the Berlin definition, and the diagnosis was established only in patients with a consistent diagnosis. The differences in each parameter were compared between patients with moderate to severe ARDS and those without or with mild ARDS. Analysis of the ability of PCT to predict moderate to severe ARDS was evaluated by receiver operator characteristic curve (ROC curve). Multivariate Logistic regression was conducted to determine the risk factors of the development of moderate to severe ARDS. RESULTS: 108 patients were finally enrolled, including 37 patients with mild ARDS (34.3%), 35 patients with moderate ARDS (32.4%), 2 patients with severe ARDS (1.9%), and 34 patients without ARDS. Compared with patients with no or mild ARDS, patients with moderate to severe ARDS were older (years old: 58.5±11.1 vs. 52.8±14.8, P < 0.05), with a higher proportion of combined hypertension [45.9% (17/37) vs. 25.4% (18/71), P < 0.05], longer operative time (minutes: 363.2±120.6 vs. 313.5±97.6, P < 0.05), and higher mortality (8.1% vs. 0, P < 0.05), but there were no differences in the VIS score, incidence of acute renal failure (ARF), CPB duration, aortic clamp duration, and intraoperative bleeding, transfusion volume, and fluid balance between the two groups. Serum PCT and NT-proBNP levels in patients with moderate to severe ARDS at postoperative day 1 were significantly higher than those in patients with no or mild ARDS [PCT (µg/L): 16.33 (6.96, 32.56) vs. 2.21 (0.80, 5.76), NT-proBNP (ng/L): 2 405.0 (1 543.0, 6 456.5) vs. 1 680.0 (1 388.0, 4 667.0), both P < 0.05]. ROC curve analysis showed that the area under the curve (AUC) for PCT to predict the occurrence of moderate to severe ARDS was 0.827 [95% confidence interval (95%CI) was 0.739-0.915, P < 0.05]. When PCT cut-off value was 7.165 µg/L, the sensitivity was 75.7% and the specificity was 84.5%, for differentiating patients who developed moderate to severe ARDS from who did not. Multivariate Logistic regression showed that age and the elevated PCT concentration were independent risk factors for the development of moderate to severe ARDS [age: odds ratio (OR) = 1.105, 95%CI was 1.037-1.177, P = 0.002; PCT: OR = 48.286, 95%CI was 10.282-226.753, P < 0.001]. CONCLUSIONS: Patients with moderate to severe ARDS undergoing CPB cardiac surgery have a higher serum concentration of PCT than patients with no or mild ARDS. Serum PCT level may be a promising biomarker to predict the development of moderate to severe ARDS, the cut-off value is 7.165 µg/L.

Optimization of central venous pressure during the perioperative period is associated with improved prognosis of high-risk operation patients.

Background: While central venous pressure (CVP) measurement is used to guide fluid management for high-risk surgical patients during the perioperative period, its relationship to patient prognosis is unknown. Methods: This single-center, retrospective observational study enrolled patients undergoing high-risk surgery from February 1, 2014 to November 31, 2020, who were admitted to the surgical intensive care unit (ICU) directly after surgery. Patients were divided into the following three groups according to the first CVP measurement (CVP1) after admission to the ICU: low, CVP1 <8 mmHg; moderate, 8 mmHg≤ CVP1 ≤ 12 mmHg; and high, CVP1 >12 mmHg. Perioperative fluid balance, 28-day mortality, length of stay in the ICU, and hospitalization and surgical complications were compared across groups. Results: Of the 775 high-risk surgical patients enrolled in the study, 228 were included in the analysis. Median (interquartile range) positive fluid balance during surgery was lowest in the low CVP1 group and highest in the high CVP1 group (low CVP1: 770 [410, 1205] mL; moderate CVP1: 1070 [685, 1500] mL; high CVP1: 1570 [1008, 2000] mL; all P <0.001). The volume of positive fluid balance during the perioperative period was correlated with CVP1 (r=0.336, P <0.001). The partial arterial pressure of oxygen(PaO2)/fraction of inspired oxygen(FiO2) ratio was significantly lower in the high CVP1 group than in the low and moderate CVP1 groups (low CVP1: 400.0 [299.5, 443.3] mmHg; moderate CVP1: 362.5 [330.0, 434.9] mmHg; high CVP1: 335.3 [254.0, 363.5] mmHg; all P <0.001). The incidence of postoperative acute kidney injury (AKI) was lowest in the moderate CVP1 group (low CVP1: 9.2%; moderate CVP1: 2.7%; high CVP1: 16.0%; P=0.007). The proportion of patients receiving renal replacement therapy was highest in the high CVP1 group (low CVP1: 1.5%; moderate CVP1: 0.9%; high CVP1: 10.0%; P=0.014). Logistic regression analysis showed that intraoperative hypotension and CVP1 >12 mmHg were risk factors for AKI within 72 h after surgery (adjusted odds ratio[aOR]=3.875, 95% confidence interval[CI]: 1.378-10.900, P=0.010 and aOR=1.147, 95%CI: 1.006-1.309, P=0.041). Conclusions: CVP that is either too high or too low increases the incidence of postoperative AKI. Sequential fluid therapy based on CVP after patients are transferred to the ICU post-surgery does not reduce the risk of organ dysfunction caused by an excessive amount of intraoperative fluid. However, CVP can be used as a safety limit indicator for perioperative fluid management in high-risk surgical patients.

The role of optical coherence tomography angiography in distinguishing ischemic versus non-ischemic central retinal vein occlusion.

INTRODUCTION: To observe macular microvascular changes in patients with ischemic and non-ischemic central retinal vein occlusion (CRVO) by optical coherence tomography angiography (OCTA), and explore the value of OCTA in differentiating ischemic and non-ischemic CRVO. METHODS: Cross sectional study. Fifty patients diagnosed as CRVO with macular edema were included. Macular edema in all patients were regressive after three consecutive anti-VEGF treatment. Patients were divided into ischemic and non-ischemic group according to ultra-wide-angle fundus fluorescein angiography (UWFFA). All patients underwent BCVA, IOP, color fundus photography, UWFFA and OCTA. The following parameters were measured: (1) Vessel density (VD): superficial and deep whole VD (SVD, DVD), superficial and deep central fovea VD (SFVD, DFVD), superficial and deep parafoveal VD (SPFVD, DPFVD); (2) Central foveal retinal thickness (CRT); (3) Area of foveal avascular zone (FAZ), perimeter of FAZ (PERIM), avascular index of FAZ (AI) and VD within a width of 300 microns around the FAZ region (FD-300). Comparison between ischemic and non-ischemic group was performed by two independent sample t-tests. Receiver operating characteristic (ROC) curve analysis was used to measure the area under the curve (AUC) of VD for predicting ischemic CRVO. RESULTS: There were no significant differences in IOP, SFVD, DFVD and CRT between ischemic and non-ischemic group, and significant differences in age, BCVA, SVD, SPFVD, DVD, DPFVD, FAZ area, PERIM, AI and FD-300 between ischemic and non-ischemic group. ROC curve analysis showed AUC of DVD and DPFVD in predicting ischemic CRVO was highest (0.962). the threshold was 38.40%, and the sensitivity was 100%, but the specificity of DVD (92.3%) was significantly higher than that of DPFVD (84.6%). Therefore, DVD ≤ 38.40% can be used as the best threshold for determining ischemic CRVO. CONCLUSION: OCTA can quantitatively evaluate the macular microvascular structure of CRVO, which is helpful to distinguish ischemic from non-ischemic CRVO.

Identification of Diagnostic Signatures and Immune Cell Infiltration Characteristics in Rheumatoid Arthritis by Integrating Bioinformatic Analysis and Machine-Learning Strategies.

Background: Rheumatoid arthritis (RA) refers to an autoimmune rheumatic disease that imposes a huge burden on patients and society. Early RA diagnosis is critical to preventing disease progression and selecting optimal therapeutic strategies more effectively. In the present study, the aim was at examining RA's diagnostic signatures and the effect of immune cell infiltration in this pathology. Methods: Gene Expression Omnibus (GEO) database provided three datasets of gene expressions. Firstly, this study adopted R software for identifying differentially expressed genes (DEGs) and conducting functional correlation analyses. Subsequently, we integrated bioinformatic analysis and machine-learning strategies for screening and determining RA's diagnostic signatures and further verify by qRT-PCR. The diagnostic values were assessed through receiver operating characteristic (ROC) curves. Moreover, this study employed cell-type identification by estimating relative subsets of RNA transcript (CIBERSORT) website for assessing the inflammatory state of RA, and an investigation was conducted on the relationship of diagnostic signatures and infiltrating immune cells. Results: On the whole, 54 robust DEGs received the recognition. Lymphocyte-specific protein 1 (LSP1), Granulysin (GNLY), and Mesenchymal homobox 2 (MEOX2) (AUC = 0.955) were regarded as RA's diagnostic markers and showed their statistically significant difference by qRT-PCR. As indicated from the immune cell infiltration analysis, resting NK cells, neutrophils, activated NK cells, T cells CD8, memory B cells, and M0 macrophages may be involved in the development of RA. Additionally, all diagnostic signatures might be different degrees of correlation with immune cells. Conclusions: In conclusion, LSP1, GNLY, and MEOX2 are likely to be available in terms of diagnosing and treating RA, and the infiltration of immune cells mentioned above may critically impact RA development and occurrence.

Performance of Lactate and CO2-Derived Parameters in Predicting Major Postoperative Complications After Cardiac Surgery With Cardiopulmonary Bypass: Protocol of a Diagnostic Accuracy Study.

Background: CO2-derived parameters are increasingly used to identify either low-flow status or anaerobic metabolism in shock resuscitation. However, the performance of CO2-derived parameters in cardiac surgical patients is poorly understood. This study aims to compare the performance of lactate and CO2-derived parameters in predicting major postoperative complications after cardiac surgery with cardiopulmonary bypass. Methods: This is a prospective, single-center, diagnostic accuracy study. All patients who receive elective cardiac surgery involving cardiopulmonary bypass will be screened for study eligibility. Blood samples will be taken for the calculation of CO2-derived parameters, including the venous-arterial difference in CO2 partial pressure (PCO2 gap), venous-arterial difference in CO2 content to arterial-venous O2 content ratio (Cv-aCO2/Ca-vO2), and venous-arterial difference in CO2 partial pressure to arterial-venous O2 content ratio (Pv-aCO2/Ca-vO2) at ICU admission, and 3, 6, and 12 h later. Baseline, perioperative data will be collected daily for 7 days; patients will be followed up for 28 days to collect outcome data. The primary endpoint is the occurrence of major postoperative complications. Receiver-operating characteristics (ROC) curve analysis will be carried out to assess the predictive performance of lactate and CO2-derived parameters. The performance of the ROC curves will be compared. Discussion: The performance of lactate and CO2-derived parameters in predicting major postoperative complications will be investigated in the non-sepsis population, which has not been extensively investigated. Our study will compare the two surrogates of respiratory quotient directly, which is an important strength. Trial Registration: ChiCTR, ChiCTR2000029365. Registered January 26th, 2020, http://www.chictr.org.cn/showproj.aspx?proj=48744.

Proteomic Analysis of Plasma sEVs Reveals That TNFAIP8 Is a New Biomarker of Cell Proliferation in Diabetic Retinopathy.

Small extracellular vesicles (sEVs) derived from the plasma have been increasingly recognized as important vehicles of intercellular communication and potential sources of new biomarkers for multiple diseases. In this study, proteomic profiles of plasma sEVs from normal subjects and diabetic patients with or without diabetic retinopathy (DR) were systematically compared using iTRAQ-based quantitative proteomics. Among a total of 901 identified proteins in plasma sEVs (false discovery rate (FDR) < 1%), 90 proteins were found to have significantly changed levels in DR. Based on the findings from the proteomic analysis, the role of tumor necrosis factor-α-induced protein 8 (TNFAIP8) in promoting human retinal microvascular endothelial cell (HRMEC) proliferation was investigated. The enzyme-linked immunosorbent assay (ELISA) showed that TNFAIP8 levels in plasma sEVs and vitreous are elevated in DR, whereas not statistically different in large EVs (lEVs) and plasma. In addition, in vitro experiments demonstrated that 4-hydroxynonenal (4-HNE) increased the expression of TNFAIP8 in HRMECs. TNFAIP8 significantly increased HRMECs cell viability and promote cell migration and tube formation, and the depletion of TNFAIP8 impaired HRMEC proliferation. We demonstrated that TNFAIP8 in plasma sEVs could be used as a potential biomarker of DR. Functional studies suggested that TNFAIP8 might be an important mediator of angiogenesis in DR.

The effect of musical interventions in improving short-term pain outcomes following total knee replacement: a meta-analysis and systematic review.

BACKGROUND: A growing number of patients continue to receive total knee replacement (TKR) surgery. Nevertheless, such surgeries result in moderate to severe postoperative pain and difficulty in managing it. Musical interventions are regarded as a type of multimodal analgesia, achieving beneficial results in other clinical treatments. This study aims to evaluate the effect of musical interventions in improving short-term pain outcomes following TKR in order to determine a more reasonable and standard way of delivering musical intervention. METHODS: A systematic search was conducted to identify available and relevant randomized controlled trials (RCTs) regarding musical interventions compared against non-musical interventions in patients treated with TKR in Embase, MEDLINE, Cochrane Library, Web of Science, CNKI, and Wanfang Med Online up to 8 January 2020. The authors independently assessed study eligibility and risk of bias and collected the outcomes of interest to analyze. The statistical analysis was conducted using the Review Manager (RevMan) version 5.30 software. RESULTS: Eight RCTs comprised of 555 patients satisfied the inclusion criteria and were enrolled in the present study. The results showed no significant difference between the music and control groups in pain of the visual analog scale (VAS), during postoperative recovery room, back to the ward after surgery; anxiety degree of VAS; heart rate; respiratory rate; oxygen saturation; blood pressure, systolic blood pressure, and diastolic blood pressure. Nevertheless, significant differences were observed between the two groups in average increase in continuous passive motion (CPM) angles and LF/HF ratio (one kind index of heart rate variability). CONCLUSIONS: Musical interventions fail to demonstrate an obvious effect in improving short-term pain outcomes following TKR. A reasonable standardization of musical interventions, including musical type, outcome measures used, outcomes measured, duration, timing and headphones or players, may improve pain outcomes with certain advantages and should be further explored after TKR.

Network pharmacology-based prediction of the active ingredients and mechanism of Shen Gui capsule for application to coronary heart disease.

BACKGROUND: Shen Gui capsule (SGC) is a new national drug in China that is widely used in clinical practice and has significant therapeutic effects on coronary heart disease (CHD). However, its active ingredients and mechanism of action for treating coronary heart disease remain unknown. Therefore, the purpose of this paper is to systematically explore the mechanism and efficacy of SGC in the "multicomponent-multitarget- multipathway" treatment for CHD using network pharmacology technology. METHODS: The potential active ingredients of SGC were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and screened by pharmacokinetic parameters. Their possible targets were predicted using the TCMSP and DrugBank database. The CHD-related targets were identified from Comparative Toxicogenomics Database (CTD), UniProt, and PharmGKB database. The compound-target-disease network was constructed using Cytoscape for visualization. Additionally, the protein functional annotation and identification of signaling pathways of potential targets were performed by Gene Ontology (GO) and KEGG enrichment analysis using the Metascape platform. RESULTS: The 61 active ingredients of SGC were found to regulate neuroactive ligand-receptor interaction, fluid shear stress and atherosclerosis, estrogen signaling pathway and other pathways through 62 targets. SGC is involved in regulating the circulatory system, nervous system and immune system and other aspects of the body, and thus plays a significant role in the treatment of CHD and its complications, showing the mechanism of SGC's "multicomponent, multitarget, and multipathway" prevention and treatment of CHD. In addition, three predictive components were first found to have potential biological activity by this method. CONCLUSION: The studies we have performed successfully predict the effective components and potential targets of SGC in the prevention and treatment of CHD, which helped to systematically clarify its mechanism of action and provided a direction for future research on the modern mechanism of SGC in the treatment of CHD.

The fellow eye effect of unilateral intravitreal conbercept injections in eyes with diabetic macular edema.

AIMS: To investigate whether intravitreal conbercept injection affects contralateral untreated eyes in bilateral diabetic macular edema (DME) patients. METHODS: In this retrospective study, 15 patients (30 eyes) with type 2 diabetes were followed after bilateral DME diagnosis in the Department of Ophthalmology, Peking Union Medical College Hospital from 2015 to 2018. Patients underwent examinations including best corrected visual acuity (BCVA), slit-lamp microscopy, indirect ophthalmoscope, color fundus photography, fundus fluorescein angiography, optical coherence tomography, and glycated hemoglobin (HbA1c). Each patient received conbercept (0.5 mg) intravitreally in the severe eye. Nonparametric Wilcoxon signed-rank tests and Pearson's correlation coefficient were used to assess changes in BCVA and central retinal thickness (CRT) and relations between BCVA changes in treated and untreated eyes, respectively. RESULTS: The mean follow-up time was 10.60 ± 2.29 months, and the mean injection number of 15 treated eyes was 9.13 ± 0.68. HbA1c remained below 10% during treatment with no significant changes between the initial and final visits (7.81 ± 1.17 vs 7.62 ± 1.19%) (P = 0.576). In untreated eyes, CRT significantly decreased from the initial to final visits (368.93 ± 125.45 vs 306.27 ± 89.70 µm) (P = 0.028). In untreated eyes, BCVA showed no significant difference between the initial and final visits (0.38 ± 0.30 vs 0.40 ± 0.30 logMAR) (P = 0.937), but BCVA changes in treated and untreated eyes were positively correlated (r = 0.527, P = 0.044). CONCLUSIONS: Intravitreal conbercept injection results in decreased CRT and increased BCVA in untreated eyes, which is consistent with the changes in treated eyes for patients with bilateral DME.

SRV2 promotes mitochondrial fission and Mst1-Drp1 signaling in LPS-induced septic cardiomyopathy.

Mitochondrial fission is associated with cardiomyocyte death and myocardial depression, and suppressor of ras val-2 (SRV2) is a newly discovered pro-fission protein. In this study, we examined the mechanisms of SRV2-mediated mitochondrial fission in septic cardiomyopathy. Western blotting, ELISA, and immunofluorescence were used to evaluate mitochondrial function, oxidative balance, energy metabolism and caspase-related death, and siRNA and adenoviruses were used to perform loss- and gain-of-function assays. Our results demonstrated that increased SRV2 expression promotes, while SRV2 knockdown attenuates, cardiomyocyte death in LPS-induced septic cardiomyopathy. Mechanistically, SRV2 activation promoted mitochondrial fission and physiological abnormalities by upregulating oxidative injury, ATP depletion, and caspase-9-related apoptosis. Our results also demonstrated that SRV2 promotes mitochondrial fission via a Mst1-Drp1 axis. SRV2 knockdown decreased Mst1 and Drp1 levels, while Mst1 overexpression abolished the mitochondrial protection and cardiomyocyte survival-promoting effects of SRV2 knockdown. SRV2 is thus a key novel promotor of mitochondrial fission and Mst1-Drp1 axis activity in septic cardiomyopathy.

Resveratrol Protects the Myocardium in Sepsis by Activating the Phosphatidylinositol 3-Kinases (PI3K)/AKT/Mammalian Target of Rapamycin (mTOR) Pathway and Inhibiting the Nuclear Factor-κB (NF-κB) Signaling Pathway.

BACKGROUND Sepsis combined with myocardial injury is an important cause of septic shock and multiple organ failure. However, the molecular mechanism of sepsis-induced myocardial dysfunction has not yet been thoroughly studied. Resveratrol has been an important research topic due its organ-protection function, but the specific mechanism is unclear. The purpose of this study was to explore the mechanism of organ injury in sepsis and to investigate the molecular mechanism of resveratrol in myocardial protection in sepsis. MATERIAL AND METHODS A classical Sprague-Dawley rat model of sepsis peritonitis was constructed for further experiments. The PI3K inhibitor LY294002 and resveratrol were used to intervene in a rat model of cardiomyopathy. HE staining was used to observe pathological changes. Cardiomyocyte apoptosis was detected by TUNEL assay. Western blot analysis was used to detect the level of maker proteins. RESULTS The PI3K inhibitors could promote cardiac abnormalities and apoptosis, but resveratrol showed the opposite effect. The upregulation function of the PI3K inhibitor on the expression of NF-kappaB, IL-6, IL-1ß, and TLR4 in LPS rats was not obvious, but the expression of TNF-a in LPS+LY294002 rats was increased by 22.85% compared with that in LPS rats (P<0.05). Compared with the LPS group, the expression of NF-kappaB, TNF-alpha, IL-6, IL-1ß, and TLR4 in the LPS+resveratrol group was decreased. The expression of p-PI3K, p-AKT, and p-mTOR in LPS+LY294002 was reduced. The expression p-PI3K, p-AKT, and p-mTOR in the myocardium of the LPS+resveratrol group was increased. CONCLUSIONS Resveratrol can protect the myocardium in sepsis by activating the PI3K/AKT/mTOR signaling pathway and inhibiting the NF-kappaB signaling pathway and related inflammatory factors.

Sepsis-related myocardial injury is associated with Mst1 upregulation, mitochondrial dysfunction and the Drp1/F-actin signaling pathway.

LPS-induced septic cardiomyopathy has been found to be connected with mitochondrial stress through unknown mechanisms. Mitochondrial fission is an early event in mitochondrial dysfunction. The aim of our study was to determine the role and regulatory mechanism of mitochondrial fission in the progression of LPS-induced septic cardiomyopathy, with a particular focus on Mst1 and F-actin. Our data demonstrated that Mst1 expression was rapidly upregulated in LPS-treated hearts and that increased Mst1 promoted cardiomyocyte death by inducing mitochondrial stress. Mechanistically, elevated expression of Mst1 upregulated Drp1, and the latter initiated mitochondrial fission. Excessive mitochondrial fission caused mitochondrial oxidative injury, mitochondrial membrane potential reduction, mitochondrial proapoptotic element translocation into the cytoplasm/nucleus, mitochondrial energy dysfunction and mitochondrial apoptosis activation. Inhibition of mitochondrial fission sustained mitochondrial function and favored cardiomyocyte survival. Furthermore, we identified F-actin degradation as an apparent downstream event of mitochondrial fission activation in the context of LPS-induced septic cardiomyopathy. Stabilization of F-actin attenuated fission-mediated cardiomyocyte death. Altogether, our results define the Mst1/Drp1/mitochondrial fission/F-actin axis as a new signaling pathway that mediates LPS-related septic cardiomyopathy by inducing mitochondrial stress and cardiomyocyte death. Therefore, Mst1 expression, mitochondrial fission modification and F-actin stabilization may serve as potential therapeutic targets for sepsis-related myocardial injury.

Impact of CYP2A6 gene polymorphism on the pharmacokinetics of dexmedetomidine for premedication.

BACKGROUND: Dexmedetomidine is a widely used sedative in clinic, which is mainly metabolized by cytochrome P450 2A6 (CYP2A6). Dexmedetomidine was rarely reported for off-label usage of premedication, but lacking relevant pharmacokinetic investigations. Therefore, our study determined the dexmedetomidine pharmacokinetics of CYP2A6*4 allele in Chinese patients pretreated with dexmedetomidine whose mutation frequency of CYP2A6*4 are high, in order to provide clinical references. METHODS: Thirty-one elective surgery patients received premedication with 0.5 µg/kg dexmedetomidine via intravenous pump. Their plasma concentrations at multiple time-points and polymorphism of CYP2A6*4 were determined and statistically analyzed. RESULTS: 9 patients were *1/*4 or *4/*4, and 22 patients were *1/*1. The main pharmacokinetic parameters were area under curve (AUC) 1396.19 ± 332.47h· ng· l-1, peak blood concentration (Cmax) 495.50 ± 104.90ng· l-1, distribution volume (V) 0.68 ± 0.20 L/kg, clearance (CL) 0.38 ± 0.11 L/h/kg, distribution half-life (t1/2α) 0.05 ± 0.01h, elimination half-life (t1/2ß) 2.53 ± 0.04h. No significant pharmacokinetic differences were found among CYP2A6*1/*1, *1/*4, and *4/*4 patients. CONCLUSIONS: In Chinese patients pretreated with dexmedetomidine, T1/2ß was consistent with that published, but T1/2α, V and Cl were lower. It was unnecessary to consider the mutation when developing the precision regimen of dexmedetomidine.

NF­κB regulates HSF1 and c­Jun activation in heat stress­induced intestinal epithelial cell apoptosis.

Heat stress may induce intestinal epithelial cell apoptosis; however, the molecular mechanisms have not yet been identified. The present study used IEC­6 rat small intestinal epithelial cells to investigate heat stress­induced production of reactive oxygen species (ROS), which may be involved in nuclear factor (NF)­κB activation during heat stress. IEC­6 cells were transfected with NF­κB p65­specific small interfering RNA (siRNA), and observed a significant increase in cell apoptosis and caspase­3 cleavage; however, in cells transfected with adenovirus that constitutively overexpressed p65, the opposite results were obtained. Furthermore, p65 knockdown increased the heat stress­induced expression and activity of heat shock transcription factor 1 (HSF1); conversely, p65 overexpression slightly decreased HSF1 activity. The levels of heat stress­induced c­Jun phosphorylation were also examined: Knockdown of p65 resulted in a reduction of c­Jun phosphorylation, whereas p65 overexpression resulted in increased phosphorylation. Furthermore, siRNA­mediated knockdown of HSF1 in IEC­6 cells significantly increased heat stress­induced apoptosis. Cells pretreated with c­Jun peptide, an inhibitor of c­Jun activation, exhibited a significant reduction in apoptosis. These findings indicated that heat stress stimulation in IEC­6 cells induced the pro­apoptotic role of NF­κB by regulating HSF1 and c­Jun activation.

[Risk factors for acute respiratory distress syndrome following surgeries for pediatric critical and complex congenital heart disease].

OBJECTIVE: To explore the risk factors for acute respiratory distress syndrome (ARDS) in children receiving surgeries for critical and complex congenital heart disease (CCHD). METHODS: According to the 2011's Berlin definition of ARDS, the clinical data were collected from 75 children without ARDS (group I) and 80 children with ARDS (group II) following surgeries for CCHD performed in the Department of Cardiac Surgery of our hospital from January, 2009 to May, 2014. Univariate analyses and logistic regression were used to analyze the risk factors contributing to the occurrence of ARDS following the surgeries. RESULTS: In the 80 patients who developed ARDS postoperatively in group II, 27 had mild ARDS, 25 had moderate ARDS, and 28 had severe ARDS; death occurred in 17 (21%) cases. Univariate analyses showed that 23 parameters were significantly different between groups I and II (P<0.05), including weight; preoperative PCO2, left ventricular ejection fraction, pulmonary artery pressure, pulmonary infection, and coagulation abnormalities; early postoperative serum globulin; intraoperative aortic cross clamp (ACC) time; cardiopulmonary bypass (CPB) time; operation time; blood loss and blood transfusion amount intraoperatively and during the first 8 h after operation; lactic acid level immediately after the operation and its maximum increasing rate within 24 h postoperatively; postoperative serum levels of albumin and creatinine; serum levels of B-type natriuretic peptide, procalcitonin, C-reactive protein, and prealbumin 24 h after operation; and age. Logistic regression analyses showed that intraoperative ACC time, CPB time, the maximum increasing rate of lactic acid within 24 h after operation, serum procalcitonin 24 h after operation and intraoperative blood loss were independent risk factors for postoperative ARDS. CONCLUSION: The risk factors of ARDS identified in these children can predict the occurrence of ARDS following the surgeries and timely interventions can improve the success rate in treatment of postoperative ARDS in children with CCHD.

Lung-protective Ventilation in Patients with Brain Injury: A Multicenter Cross-sectional Study and Questionnaire Survey in China.

BACKGROUND: Over the years, the mechanical ventilation (MV) strategy has changed worldwide. The aim of the present study was to describe the ventilation practices, particularly lung-protective ventilation (LPV), among brain-injured patients in China. METHODS: This study was a multicenter, 1-day, cross-sectional study in 47 Intensive Care Units (ICUs) across China. Mechanically ventilated patients (18 years and older) with brain injury in a participating ICU during the time of the study, including traumatic brain injury, stroke, postoperation with intracranial tumor, hypoxic-ischemic encephalopathy, intracranial infection, and idiopathic epilepsy, were enrolled. Demographic data, primary diagnoses, indications for MV, MV modes and settings, and prognoses on the 60th day were collected. Multivariable logistic analysis was used to assess factors that might affect the use of LPV. RESULTS: A total of 104 patients were enrolled in the present study, 87 (83.7%) of whom were identified with severe brain injury based on a Glasgow Coma Scale ≤8 points. Synchronized intermittent mandatory ventilation (SIMV) was the most frequent ventilator mode, accounting for 46.2% of the entire cohort. The median tidal volume was set to 8.0 ml/kg (interquartile range [IQR], 7.0-8.9 ml/kg) of the predicted body weight; 50 (48.1%) patients received LPV. The median positive end-expiratory pressure (PEEP) was set to 5 cmH2O (IQR, 5-6 cmH2O). No PEEP values were higher than 10 cmH2O. Compared with partially mandatory ventilation, supportive and spontaneous ventilation practices were associated with LPV. There were no significant differences in mortality and MV duration between patients subjected to LPV and those were not. CONCLUSIONS: Among brain-injured patients in China, SIMV was the most frequent ventilation mode. Nearly one-half of the brain-injured patients received LPV. Patients under supportive and spontaneous ventilation were more likely to receive LPV. TRIAL REGISTRATION: ClinicalTrials.org NCT02517073 https://clinicaltrials.gov/ct2/show/NCT02517073.

Better short-term efficacy of treating severe flail chest with internal fixation surgery compared with conservative treatments.

BACKGROUND: The objective of the study is to provide evidence for selecting the best treatment approach for severe flail chest by comparing surgical and conservative treatments. METHODS: This is a retrospective study in which 32 patients with severe flail chest were treated in the Fujian Provincial Hospital (China) between July 2007 and July 2012 with surgical internal rib fixation (n = 17) or conservative treatments (n = 15). Mechanical ventilation time, intensive care unit (ICU) stay time, pulmonary infection, antibiotic treatment duration, acute physiology and chronic health evaluation II (APACHE II) scores 7 and 14 days after trauma, rate of tracheostomy, and rate of endotracheal re-intubation were compared. RESULTS: One patient died in the conservative treatment group. Better short-term outcomes were observed in the surgery group, such as total mechanical ventilation time (10.5 ± 3.7 vs. 13.7 ± 4.4 days, P = 0.03), ICU stay (15.9 ± 5.0 vs. 19.6 ± 5.0 days, P = 0.05), pulmonary infection rate (58.8 % vs. 93.3 %, P = 0.02), and APACHE II scores on the 14th day (6.5 ± 3.8 vs. 10.1 ± 4.7, P = 0.02). No difference was observed in the therapeutic time of antibiotics, rate of tracheostomy, and the rate of endotracheal re-intubation between the two groups. CONCLUSIONS: Results suggest that internal fixation surgery resulted in better outcomes in the management of severe flail chest compared with conservative treatments.

Emergence agitation during recovery from intracranial surgery under general anaesthesia: a protocol and statistical analysis plan for a prospective multicentre cohort study.

INTRODUCTION: Emergence agitation after intracranial surgery is an important clinical issue during anaesthesia recovery. The aim of this multicentre cohort study is to investigate the incidence of emergence agitation, identify the risk factors and determine clinical outcomes in adult patients after intracranial surgery under general anaesthesia. Additionally, we will deliberately clarify the relationship between postoperative pneumocephalus and agitation. METHODS AND ANALYSIS: The present study is a prospective multicentre cohort study. Five intensive care units (ICUs) in China will participate in the study. Consecutive adult patients admitted to the ICUs after intracranial surgery will be enrolled. Sedation-Agitation Scale (SAS) or Richmond Agitation-Sedation Scale (RASS) will be used to evaluate the patients 12 h after the enrolment. Agitation is defined as an SAS score of 5-7, or an RASS score of +2 to +4. According to the maximal SAS and RASS score, patients will be divided into two cohorts: the agitation group and the non-agitation group. Factors potentially related to emergence agitation will be collected at study entry, during anaesthesia and operation, during postoperative care. Univariate analyses between the agitation and the non-agitation groups will be performed. The stepwise backward logistic regression will be carried out to identify the independent predictors of agitation. Patients will be followed up for 72 h after the operation. Accidental self-extubation of the endotracheal tube and removal of other catheters will be documented. The use of sedatives and analgesics will be collected. ETHICS AND DISSEMINATION: Ethics approval has been obtained from each of five participating hospitals. Study findings will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT02318199.

Procalcitonin as a predictor of moderate to severe acute respiratory distress syndrome after cardiac surgery with cardiopulmonary bypass: a study protocol for a prospective cohort study.

INTRODUCTION: Procalcitonin (PCT) is activated during cardiopulmonary bypass (CPB) and may be a predictor of acute respiratory distress syndrome (ARDS). The objective of this study is to determine whether patients with different serum PCT concentrations exhibit different rates of developing moderate to severe ARDS. METHODS AND ANALYSIS: This is a prospective, single centre, observational cohort study. All patients admitted to the cardiosurgery department for cardiac surgery with CPB were screened for study eligibility. All eligible patients received a CPB procedure. Blood samples were obtained to determine white cell counts as well as N-terminal pro-B-type natriuretic peptide, C reactive protein and PCT levels. Patients were assigned to the PCT elevated cohort or the control cohort based on serum PCT concentrations on the first postoperative day with a cut-off value of 7.0 ng/mL. Data, including baseline, perioperative and outcome data, were collected daily for 7 days. The primary end point was the incidence of moderate to severe ARDS, which was diagnosed according to the Berlin definition. ETHICS AND DISSEMINATION: The study was approved by the Institutional Review Board of Fujian Provincial Hospital. Study findings are disseminated through peer-reviewed publications and conference presentations. STUDY REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-OCH-14005076).