PDTC improves cognitive impairment in LPS-induced ARDS by regulating miR-181c/NF-κB axis-mediated neuroinflammation.

BACKGROUND: Cognitive impairment is a severe complication of acute respiratory distress syndrome (ARDS). Emerging studies have revealed the effects of pyrrolidine dithiocarbamate (PDTC) on improving surgery-induced cognitive impairment. The major aim of the study was to investigate whether PDTC protected against ARDS-induced cognitive dysfunction and to identify the underlying mechanisms involved. METHODS: The rat model of ARDS was established by intratracheal instillation of lipopolysaccharide (LPS), followed by treatment with PDTC. The cognitive function of rats was analyzed by the Morris Water Maze, and pro-inflammatory cytokines were assessed by quantitative real-time PCR, enzyme-linked immunosorbent assay, and western blot assays. A dual-luciferase reporter gene assay was performed to identify the relationship between miR-181c and its target gene, TAK1 binding protein 2 (TAB2). RESULTS: The results showed that PDTC improved cognitive impairment and alleviated neuroinflammation in the hippocampus in LPS-induced ARDS model. Furthermore, we demonstrated that miR-181c expression was downregulated in the hippocampus of the ARDS rats, which was restored by PDTC treatment. In vitro studies showed that miR-181c alleviated LPS-induced pro-inflammatory response by inhibiting TAB2, a critical molecule in the nuclear factor (NF)-κB signaling pathway. CONCLUSION: PDTC improves cognitive impairment in LPS-induced ARDS by regulating miR-181c/NF-κB axis-mediated neuroinflammation, providing a potential opportunity for the treatment of this disease.

[Curcumin alleviates nuclear factor-κB/NOD-like receptor protein 3 mediated renal injury caused by acute respiratory distress syndrome through reducing mitochondrial oxidative stress].

OBJECTIVE: To evaluate the effect of curcumin on renal mitochondrial oxidative stress, nuclear factor-κB/NOD-like receptor protein 3 (NF-κB/NLRP3) inflammatory body signaling pathway and tissue cell injury in rats with acute respiratory distress syndrome (ARDS). METHODS: A total of 24 specific pathogen free (SPF)-grade healthy male Sprague-Dawley (SD) rats were randomly divided into control group, ARDS model group, and low-dose and high-dose curcumin groups, with 6 rats in each group. The ARDS rat model was reproduced by intratracheal administration of lipopolysaccharide (LPS) at 4 mg/kg via aerosol inhalation. The control group was given 2 mL/kg of normal saline. The low-dose and high-dose curcumin groups were administered 100 mg/kg or 200 mg/kg curcumin by gavage 24 hours after model reproduction, once a day. The control group and ARDS model group were given an equivalent amount of normal saline. After 7 days, blood samples were collected from the inferior vena cava, and the levels of neutrophil gelatinase-associated lipocalin (NGAL) in serum were determined by enzyme-linked immunosorbent assay (ELISA). The rats were sacrificed, and kidney tissues were collected. Reactive oxygen species (ROS) levels were determined by ELISA, superoxide dismutase (SOD) activity was detected using the xanthine oxidase method, and malondialdehyde (MDA) levels were determined by colorimetric method. The protein expressions of hypoxia-inducible factor-1α (HIF-1α), caspase-3, NF-κB p65, and Toll-like receptor 4 (TLR4) were detected by Western blotting. The mRNA expressions of HIF-1α, NLRP3, and interleukin-1ß (IL-1ß) were detected by reverse transcription-polymerase chain reaction (RT-PCR). Renal cell apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL). The morphological changes in renal tubular epithelial cells and mitochondria were observed under a transmission electron microscope. RESULTS: Compared with the control group, the ARDS model group exhibited kidney oxidative stress and inflammatory response, significantly elevated serum levels of kidney injury biomarker NGAL, activated NF-κB/NLRP3 inflammasome signaling pathway, increased kidney tissue cell apoptosis rate, and renal tubular epithelial cell damage and mitochondrial integrity destruction under transmission electron microscopy, indicating successful induction of kidney injury. Following curcumin intervention, the injury to renal tubular epithelial cells and mitochondria in the rats was significantly mitigated, along with a noticeable reduction in oxidative stress, inhibition of the NF-κB/NLRP3 inflammasome signaling pathway, and a significant decrease in kidney tissue cell apoptosis rate, demonstrating a certain dose-dependency. Compared with the ARDS model group, the high-dose curcumin group exhibited significantly reduced serum NGAL levels and kidney tissue MDA and ROS levels [NGAL (µg/L): 13.8±1.7 vs. 29.6±2.7, MDA (nmol/g): 115±18 vs. 300±47, ROS (kU/L): 75±19 vs. 260±15, all P < 0.05], significantly down-regulated protein expressions of HIF-1α, caspase-3, NF-κB p65, and TLR4 in the kidney tissue [HIF-1α protein (HIF-1α/ß-actin): 0.515±0.064 vs. 0.888±0.055, caspase-3 protein (caspase-3/ß-actin): 0.549±0.105 vs. 0.958±0.054, NF-κB p65 protein (NF-κB p65/ß-actin): 0.428±0.166 vs. 0.900±0.059, TLR4 protein (TLR4/ß-actin): 0.683±0.048 vs. 1.093±0.097, all P < 0.05], and significantly down-regulated mRNA expressions of HIF-1α, NLRP3, and IL-1ß [HIF-1α mRNA (2-ΔΔCt): 2.90±0.39 vs. 9.49±1.87, NLRP3 mRNA (2-ΔΔCt): 2.07±0.21 vs. 6.13±1.32, IL-1ß mRNA (2-ΔΔCt): 1.43±0.24 vs. 3.95±0.51, all P < 0.05], and significantly decreased kidney tissue cell apoptosis rate [(4.36±0.92)% vs. (27.75±8.31)%, P < 0.05], and significantly increased SOD activity (kU/g: 648±34 vs. 430±47, P < 0.05). CONCLUSIONS: Curcumin can alleviate kidney injury in ARDS rats, and its mechanism may be related to the increasing in SOD activity, reduction of oxidative stress, and inhibition of the activation of the NF-κB/NLRP3 inflammasome signaling pathway.

JNK-IN-8 treatment improves ARDS-induced cognitive impairment by inhibiting JNK/NF-κB-mediated NLRP3 inflammasome.

PURPOSE: Cognitive impairment is a critical complication of acute respiratory distress syndrome (ARDS). However, effective interventions are lacking. Growing evidence demonstrates that c-Jun N-terminal kinase (JNK)-mediated neuroinflammation is involved in the development of ARDS. Therefore, we hypothesized that the JNK pathway is involved in ARDS-induced cognitive impairment. METHODS: An in vivo rat model of ARDS was established by treating it with lipopolysaccharide. The cognitive function was assessed by behavioral tests. The levels of pro-inflammatory cytokines, JNK and NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) were analyzed by enzyme-linked immunosorbent assay, western blot, or immunohistochemical analysis. RESULTS: We found that JNK inhibitor 8 (JNK-IN-8) alleviated cognitive impairment, neuroinflammation, and NLRP3 inflammasome activation in the ARDS rat model. Additionally, an in vivo study showed that the protective effect of JNK-IN-8 on cognitive impairment was blocked by nigericin, an NLRP3 activator. CONCLUSIONS: Our data suggest that JNK-IN-8 treatment improves ARDS-induced cognitive impairment by inhibiting the JNK/nuclear factor-κB-mediated NLRP3 inflammasome.

Theacrine alleviates sepsis-induced acute kidney injury by repressing the activation of NLRP3/Caspase-1 inflammasome.

Acute kidney injury (AKI) is a frequent and serious complication of sepsis, which results in a rapid decline of kidney function. Currently, there are no curative therapies for AKI. Theacrine is a purine alkaloid and exerts significant role in regulating inflammation, oxidative stress, and mood elevation. The study aims to evaluate the biological role and potential mechanism of theacrine in septic AKI. The murine and cellular models of septic AKI were established in lipopolysaccharide (LPS)-treated C57BL/6 mice and HK-2 cells, respectively. The effect of theacrine on alleviating septic AKI was assessed after pretreatment with theacrine in vivo and in vitro. We found that theacrine treatment significantly alleviated LPS-induced kidney injury, as evidenced by decreased levels of kidney injury markers (blood urea nitrogen and creatinine), inflammatory factors (IL-1ß and IL-18), and cell apoptosis in vivo and in vitro. Mechanistically, theacrine markedly repressed the activation of NOD-like receptor (NLR) pyrin domain-containing protein 3 (NLRP3)inflammasome. As expected, MCC950 (a specific inhibitor of NLRP3) treatment also decreased LPS-induced production of IL-18 and IL-1ß and cell apoptosis in HK-2 cells. More important, Nigericin sodiumsalt (a NLRP3 agonist) damaged the effect of theacrine on repressing kidney injury markers (blood urea nitrogen and creatinine), pro-inflammatory cytokines (IL-18 and IL-1ß), and cell apoptosis. Taken together, these results demonstrate that theacrine alleviates septic AKI, at least in part by repressing the activation of NLRP3 inflammasome.

[Application of folding transfer shelf in the transportation of critically ill patients].

OBJECTIVE: To explore the application of folding transfer shelf in the transportation of critically ill patients. METHODS: Patients transferred from the emergency department to the intensive care unit (ICU) admitted to the First Hospital of Jiaxing from January 1st to December 31st in 2019 were enrolled. The patients were divided into study group and control group by whether or not using the self-developed folding transfer shelf. The incidence of adverse events, the stability rate of vital signs and the transport time were compared between the two group. RESULTS: A total of 437 patients were enrolled in the study, with 222 in the study group (which used the self-developed folding transfer shelf) and 215 in the control group (which used the conventional stretcher). The baseline data such as gender, age, disease status and disease severity were balanced between the two groups. The stability rate of vital signs in the study group was higher than that in the control group (89.19% vs. 82.33%, P < 0.05). The transfer time in the study group was shorter than that in the control group (minutes: 6.39±1.35 vs. 7.61±1.34, P < 0.01). The total incidence of adverse transport events in the study group was lower than that in the control group (2.25% vs. 10.23%, P < 0.01). The incidence of miscarriage of emergent materials and instrument falling in the study group were lower than those in the control group (0% vs. 2.79%, 0% vs. 2.33%, both P < 0.05). CONCLUSIONS: The folding transfer shelf could reduce the transport risk of critical ill patients, especially the risk of miscarriage and falling of rescue instrument. The application of folding transfer shelf could regulate the management of transport, keep the vital signs of patients stable during transport, shorten the transport time, and facilitate an efficient and high-quality transport.

Dynamic assessment of lung injury by ultrasound in patients with acute paraquat poisoning.

OBJECTIVE: To investigate the value of ultrasound in the dynamic assessment of lung injury after acute paraquat poisoning. METHODS: A prospective observational study was performed on patients with paraquat poisoning from admission to day 28 or discharge. Ultrasound assessment of the lungs was performtyed every 48 hours. The correlation of the lung ultrasound score (LUS) with other indicators was analyzed. RESULTS: Twenty-six patients were enrolled, with an average age of 46 ± 16 years. The average toxic dose was 95 ± 51 mL. The intensive care unit (ICU) stay averaged 9 ± 8 days, and the 28-day mortality was 88.5%. There was a significant negative correlation between LUS and oxygenation index (rho = -0.896) and a significant positive correlation between LUS and carbon dioxide concentration (rho = 0.567). Lung ultrasound and computed tomography imaging correlated closely. CONCLUSION: Lung ultrasound can reflect changes in lung status in patients with paraquat poisoning and can be used to evaluate lung injury in these patients. Trial registration: ChiCTR, ChiCTR-DDD-16010211. Registered 21 December 2016, http://www.chictr.org.cn/listbycreater.aspx .

Prognostic Value of Prolonged Feeding Intolerance in Predicting All-Cause Mortality in Critically Ill Patients: A Multicenter, Prospective, Observational Study.

BACKGROUND: The 2012 European Society of Intensive Care Medicine (ESICM) guidelines provided a clear definition of feeding intolerance (FI). The study aimed to investigate the association between FI based on the current ESICM definition and clinical outcome and to further explore the effect of the duration of FI on mortality. METHODS: Adult patients from 14 general intensive care units (ICUs) with an expected ICU stay ≥24 hours were prospectively studied. Based on FI duration in the first week of admission to the ICU, FI was categorized as 7-day persistent feeding tolerance (FT), delayed FT, delayed FI, and 7-day persistent FI. The primary outcomes were 28-day and 60-day all-cause mortality. RESULTS: Of 499 patients, the prevalence of 3-day and 7-day persistent FI was 39.2% (n = 196) and 25.4% (n = 106), respectively. The patients with 3-day FT had lower risk of 28-day and 60-day mortality rates and higher prevalence in ventilator weaning and vasoactive medication on the seventh day of ICU admission than those with 3-day FI. Three-day FI remained an independent predictor for 60-day mortality. In a subgroup analysis including 418 patients with 7-day survival, compared with those with 7-day persistent FT, the odds ratios of 60-day mortality were 1.67, 1.97, and 2.62 in the patients with delayed FT, delayed FI, and 7-day persistent FI, respectively. CONCLUSION: FI was associated with increased mortality and longer duration of mechanical ventilation and vasoactive support. Prolonged or relapsing FI represented an incremental risk of adverse outcomes in critically ill patients.

[Relationship between albumin supply and prognosis in mechanically ventilated patients: a retrospective analysis].

OBJECTIVE: To investigate the relationship between enteral nutrient albumin supply and prognosis in patients with mechanical ventilation. METHODS: The clinical data of 418 mechanically ventilated patients receiving enteral nutrition support treatment in intensive care unit (ICU) of the First Hospital of Jiaxing from January 2016 to June 2019 were retrospectively analyzed. According to whether the daily albumin supply was up to standard, the patients were divided into the standard group (albumin supply was ≥ 1.2 g×kg-1×d-1) and the non-standard group (albumin supply was < 1.2 g×kg-1×d-1). Prealbumin, transferrin levels before and after treatment, 28-day mortality, mechanical ventilation time and the length of ICU stay were compared between the two groups. RESULTS: A total of 418 patients were included, including 225 in the standard group and 193 in the non-standard group. There were no significant differences in gender, age and disease composition between the two groups, and the baseline data were comparable. There was no significant difference in daily calories between the standard group and the non-standard group (kJ/d: 119.73±31.55 vs. 110.05±28.98, P > 0.05), but the daily albumin supply of the standard group was significantly higher than that of the non-qualified group (g×kg-1×d-1: 1.38±0.83 vs. 0.95±0.75, P < 0.05). There was no significant difference in the levels of prealbumin, transferrin between the two groups before treatment. The levels of prealbumin, transferrin in standard group and non-standard group were significantly higher after treatment than before [prealbumin (mg/L): 188.53±69.25 vs. 119.44±57.62, 145.18±56.92 vs. 108.81±69.50; transferrin (g/L): 2.99±0.87 vs. 1.85±0.76, 2.09±0.81 vs. 1.52±0.76, all P < 0.05]. Moreover, prealbumin and transferring in the standard group were further improved than the non-standard group [prealbumin (mg/L): 188.53±69.25 vs. 145.18±56.92, transferrin (g/L): 2.99±0.87 vs. 2.09±0.81, both P < 0.05]. In addition, mechanical ventilation time, the length of ICU stay of the standard group were significantly shorter than those of the non-standard group (hours: 147.2±7.5 vs. 216.6±8.2, 198.8±9.5 vs. 295.4±8.9, both P < 0.05), but there was no statistically significant difference in 28-day mortality [11.56% (26/225) vs. 15.03% (29/193), P > 0.05]. CONCLUSIONS: Under the condition of standard enteral nutritional calories, increased of the albumin supply can improve the clinical nutritional status of patients with mechanical ventilation, shorten mechanical ventilation time and hospital stay.

Severity of acute gastrointestinal injury grade is a predictor of all-cause mortality in critically ill patients: a multicenter, prospective, observational study.

BACKGROUND: In 2012, the European Society of Intensive Care Medicine proposed a definition for acute gastrointestinal injury (AGI) based on current medical evidence and expert opinion. The aim of the present study was to evaluate the feasibility of using the current AGI grading system and to investigate the association between AGI severity grades with clinical outcome in critically ill patients. METHODS: Adult patients at 14 general intensive care units (ICUs) with an expected ICU stay ≥24 h were prospectively studied. The AGI grade was assessed daily on the basis of gastrointestinal (GI) symptoms, intra-abdominal pressures, and feeding intolerance (FI) in the first week of admission to the ICU. RESULTS: Among the 550 patients enrolled, 456 patients (82.9%) received mechanical ventilation, and 470 patients were identified for AGI. The distribution of the global AGI grade was 24.5% with grade I, 49.4% with grade II, 20.6% with grade III, and 5.5% with grade IV. AGI grading was positively correlated with 28- and 60-day mortality (P < 0.0001). Univariate Cox regression analysis showed that age, sepsis, diabetes mellitus, coronary artery disease, the use of vasoactive drugs, serum creatinine and lactate levels, mechanical ventilation, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and the global AGI grade were significantly (P ≤ 0.02) associated with 60-day mortality. In a multivariate analysis including these variables, diabetes mellitus (HR 1.43, 95% CI 1.03-1.87; P = 0.05), the use of vasoactive drugs (HR 1.56, 95% CI 1.12-2.11; P = 0.01), serum lactate (HR 1.15, 95% CI 1.06-1.24; P = 0.03), global AGI grade (HR 1.65, 95% CI 1.28-2.12; P = 0.008), and APACHE II score (HR 1.04, 95% CI 1.02-1.06; P < 0.001) were independently associated with 60-day mortality. In a subgroup analysis of 402 patients with 7-day survival, in addition to clinical predictors and the AGI grade on the first day of ICU stay, FI within the first week of ICU stay had an independent and incremental prognostic value for 60-day mortality (χ2 = 41.9 vs. 52.2, P = 0.007). CONCLUSIONS: The AGI grading scheme is useful for identifying the severity of GI dysfunction and could be used as a predictor of impaired outcomes. In addition, these results support the hypothesis that persistent FI within the first week of ICU stay is an independent determinant for mortality. TRIAL REGISTRATION: Chinese Clinical Trial Registry identifier: ChiCTR-OCS-13003824 . Registered on 29 September 2013.

Corrigendum: Photon-phonon Interaction in a Microfiber Induced by Optical and Electrostrictive Forces.

This corrects the article DOI: 10.1038/srep41849.

Photon-phonon Interaction in a Microfiber Induced by Optical and Electrostrictive Forces.

Stimulated Brillouin scattering (SBS) via electrostrictive force is a fundamental interaction between light and sound which limits the power in conventional optical fibers. The emergence of optical microfibers with subwavelength diameter, ultralight mass and an intense light field, provides a new platform for photon-phonon coupling, resulting in the radiation pressure mediated contribution of SBS. This study examines the optomechanical system in cylindrical coordinates, reveals the theoretically radiation pressure induced analogous, and demonstrates contrary effect compared with electrostrictive force in solid or hollow silica microfibers. The finding shows that the photon-phonon coupling, which is related to SBS, can be suppressed in a solid microfiber, and even be completely cancelled in a hollow microfiber.

Dynamic assessment of lung injury by ultrasound in a case with H7N9 influenza.

H7N9 influenza is a new emerging infection and has high mortality. Both chest radiography and computed tomography (CT) had some limitations in assessing such patients. We performed daily lung ultrasound in a patient with H7N9 influenza. Lung ultrasound and lung ultrasound score showed high consistency with CT and the progression of pneumonia. Ultrasound can be adjutant to chest radiography and CT in caring for patients with H7N9 influenza.

[The observations of curative efficacy of rhubarb combined with blood purification on treatment patients with severe acute organophosphorus pesticide poisoning].

OBJECTIVE: To observe the curative efficacy of rhubarb, montmorillonite powder combined with blood purification on treatment for patients with severe acute organophosphorus pesticide poisoning (AOPP). METHODS: 39 patients with AOPP were divided into treatment group (received the combined treatment of rhubarb, montmorillonite powder and blood purification on the basis of routine therapy, n = 21) and control group (only received the routine treatment because of financial difficulties or the will of family members, n = 18). The differences of clinical manifestations, curative effects and prognosis between two groups were compared. RESULTS: The time of consciousness recovery, the duration of mechanical ventilation and the length of stay in hospital in treatment group were (6.5 ± 1.3), (7.9 ± 2.0) and (13.1 ± 3.2) days, which were significantly shorter than those [(8.4 ± 2.4), (10.7 ± 2.9) and (16.5 ± 3.7) days] of control group (P < 0.05). In 5, 6 and 7 day after treatment,the cholinesterase (ChE) activities of treatment group were significantly higher than those of control group (P < 0.05). The total amount and using time of atropine and pyraloxime methylchloride in treatment group were significantly smaller and shorter than those in control group (P < 0.05). The death rate of treatment group was [19.0% (4/21)], which were significantly lower than that of control group [19.0% (4/21)] (P < 0.05). CONCLUSION: The combined treatment of rhubarb, montmorillonite powder and blood purification of the AOPP patients has a better curative effect.