Curcumin alleviates nuclear factor-κB/NOD-like receptor protein 3 mediated renal injury caused by acute respiratory distress syndrome through reducing mitochondrial oxidative stress / 中华危重病急救医学

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-1β (IL-1β) 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/β-actin): 0.515±0.064 vs. 0.888±0.055, caspase-3 protein (caspase-3/β-actin): 0.549±0.105 vs. 0.958±0.054, NF-κB p65 protein (NF-κB p65/β-actin): 0.428±0.166 vs. 0.900±0.059, TLR4 protein (TLR4/β-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-1β [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-1β 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.

Effect of curcumin on renal fibrosis induced by acute respiratory distress syndrome in rats / 中华急诊医学杂志

Objective:To investigate the effect of curcumin on renal fibrosis in lipopolysaccharide (LPS) induced acute respiratory distress syndrome (ARDS) in adult SD rats.Methods:Twenty-four male SD rats were randomly (random number) divided into four groups: control group, ARDS group, low dose group, and high dose group ( n=6 per group). In the control group, the rats were given atomization intratracheal of standard saline 2 mL/kg; in the ARDS group, low-dose group, and high-dose group, the rats were given atomization intratracheal of 4 mg/kg LPS; in the low-dose group, the rats were given curcumin 100 mg/d by the oral administration, and in the high-dose group, the rats were given curcumin or 200 mg/d respectively. After seven days, the rats were sacrificed. The superoxide dismutase (SOD) activity and the content of malondialdehyde (MDA) and glutathione (GSH) in renal tissue were detected by colorimetric assay. Nuclear factor kappa-B p65 (NF-κB p65) and transforming growth factor-β1 (TGF-β1) were detected by Western blot. The expression of interleukin-6 (IL-6) mRNA, proline hydroxylase 3 (PHD3) mRNA, vascular endothelial growth factor (VEGF) mRNA and erythropoietin receptor (EPOR) mRNA were detected by quantitative real-time PCR (qRT-PCR). HE staining and Masson staining were used to assess pathological damage. One-way analysis of variance was used for comparison among multiple groups and SNK method was used for comparison between two groups. Results:Compared with the control group, the SOD activity and GSH content in the ARDS group, low-dose group, and high-dose group were significantly decreased (all P<0.05); the protein expression levels of MDA, NF-κB p65, and TGF-β1 were increased significantly, and IL-6 mRNA, PHD3 mRNA, VEGF mRNA, and EPOR mRNA were significantly upregulated (all P<0.05). HE staining showed inflammatory cell infiltration, and fibrogenesis in kidney tissue, and Masson staining showed deposition of collangen-like substance. Compared with the ARDS group, SOD activity and GSH content were increased, while the protein expression of NF-κB p65 and TGF-β1, IL-6 mRNA, PHD3 mRNA, VEGF mRNA, and EPOR mRNA were decreased significantly in the low-dose group and high-dose group (all P<0.05). Curcumin therapy reduced inflammatory cellular infiltration, and the deposition of collagen-like substance in kidney tissue. Compared with the low-dose group, SOD activity and GSH content were increased in the high-dose group (all P<0.05), and the protein expression of NF-κB p65 and TGF-β1, IL-6 mRNA, PHD3 mRNA, VEGF mRNA, and EPOR mRNA were decreased significantly in the high-dose group (all P<0.05). The high-dose group exhibited a significant reduction in edema, and a decrease of the deposition of collagen-like substance in kidney tissue. Conclusions:Curcumin can inhibit the development of renal fibrosis induced by acute respiratory distress syndrome in rats, and its mechanism may be related to inhibiting the expression of inflammatory factors and enhancing hypoxia tolerance.

Application of folding transfer shelf in the transportation of critically ill patients / 中华危重病急救医学

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.

Relationship between albumin supply and prognosis in mechanically ventilated patients: a retrospective analysis / 中华危重病急救医学

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].@*Conclusion@#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.

Relationship between albumin supply and prognosis in mechanically ventilated patients: a retrospective analysis / 中华危重病急救医学

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]. Conclusion Under the condition of standard enteral nutritional calories, increased ofthe albumin supply can improve the clinical nutritional status of patients with mechanical ventilation, shorten mechanical ventilation time and hospital stay.

The association between feeding intolerance and clinical outcome in critically ill patients admitted to ICU: a multi-center prospective, observational study / 中华急诊医学杂志

Objective To investigate the prevalence of feeding intolerance (FI),and to explore the FI within 7 days of ICU admission in association with clinical outcome in critically ill patients.Methods The adult patients from 14 general ICUs in Zhejiang Province with an expected admission to ICU for at least 24h were recruited from March 2014 to August 2014,and all clinical,laboratory,and survival data were prospectively collected.The AGI (acute gastrointestinal injury) grade was daily assessed based on gastrointestinal (GI) symptoms,feeding details and organ dysfunction within the first week of ICU stay.The intra-abdominal pressures (IAP) was measured using AbViser device.Results Of 550 patients enrolled,418 were assessed in GI symptoms and feeding details within 7 days of ICU stay.The mean age and SOFA score were (65.1 ± 18.3) years and (8.96 ±4.10),respectively.Of them,355 patients (84.9％) were under mechanical ventilation support,and 37 (8.85％) received renal replacement therapy.The mean length of time for enteral feeding was (30.8 ±26.2) h,and the prevalence of FI on the 3rd and 7th day of ICU stay accounted for 39.2％ and 25.4％,respectively.Compared to those with FI within 7 days of ICU stay,the patients without FI had higher rate of successively weaning from mechanical ventilation (21.3％ vs.5.7％,P =0.003) and higher rate of withdrawal of vasoactive medication (45.5％ vs.20.0％,P =0.037),as well as lower mortality rate of 28-day (24.4％ vs.38.7％,P =0.004) and 60-day (29.6％ vs.44.3％,P =0.005).In multivariate Cox regression model with adjustment for age,sex,participant center,serum creatinine and lactate,AGI grade on the first day of ICU stay,and comorbidities,the FI within 7 days of ICU stay (x2 ≥ 7.24,P ＜ 0.01) remained to be independent predictors for 60-day mortality.After further adjusted for SOFA score,the FI within 7 days of ICU stay (HR =1.71,95％ CI:1.18-2.49;P =0.006) and AGI grade on the first day of ICU stay (HR =1.33,95 ％ CI:1.07-1.65;P =0.009) could provide independent prognostic values of 60-day mortality.Conclusions There is high rate of FI occurred within 7 days of ICU stay,and is significantly associated with worse outcome.In addition,this study also provides evidence to further support that measurement of gastrointestinal dysfunction could increase value of SOFA score in outcome prediction for the risk of 60-day mortality.

Clinical assessment of pelvic external fixation in hemodynamically unstable patients with pelvic fracture / 中国医师进修杂志

Objective To evaluate the clinical effect of emergency pelvic external fixation in hemodynamically unstable patients with pelvic fracture.Methods The clinical data of 56 hemodynamically unstable patients with pelvic fracture from January 2008 to December 2013 were selected.The changes of hemoglobin,mean arterial pressure,heart rate,serum lactate,urine volume,norepinephrine dosage before and after surgery for 24 h were compared and analyzed.Results Compared with those before surgery,the levels of hemoglobin,mean arterial pressure,serum lactate,urine volume,heart rate after surgery for 24 h were significantly improved:(109 ± 12) g/L vs.(69 ±22) g/L,(87.8 ±6.5) mmHg (1 mmHg =0.133 kPa) vs.(55.8 ± 7.7) mmHg,(6.3 ± 5.1) mmol/L vs.(10.8 ± 6.6) mmol/L,(35.9 ± 9.9) ml/h vs.(17.6 ± 8.4) ml/h,(84.2 ± 15.4) times/min vs.(146.4 ± 12.1) times/min,and the norepinephrine dosage was significantly reduced:(0.8 ± 0.2) μ g/ (kg· min) vs.(2.2 ± 0.8) μ g/ (kg· min).The differences had statistical significance (P ＜ 0.05 or ＜ 0.01).Conclusion Bedside pelvic external fixation can rapidly improve shock symptom in hemodynamically unstable patients with pelvic fracture,which is safe and efficient.

Effects of prone ventilation on extra pulmonary acute lung injury / 中国中西医结合急救杂志

Objective To investigate the effects and mechanism of prone ventilation in rats with lipopolysaccharide(LPS)-induced extra pulmonary acute lung injury(ALI). Methods Thirty-two male Sprague-Dawley(SD)rats were randomly divided into four groups:control group,ALI group,supine position group(ALIS group)and prone position group(ALIP group). The ALI animal model was reproduced by intra-peritoneal injection of LPS 6 mg/kg,and 2 mL/kg sterile saline was intra-peritoneally injected in control group. After 24 hours,the ALIS group and ALIP group were mechanically ventilated for 4 hours in supine and prone positions respectively. Arterial partial pressure of oxygen(PaO2),carbon dioxide partial pressure(PaCO2),wet to dry weight ratio of lung(W/D) were observed,and the levels of tumor necrosis factor-α(TNF-α),interleukins(IL-6,IL-10)in bronchoalveolar lavage fluid(BALF)were measured. The degrees of histopathological changes of lung were investigated and assessed under light microscope. Results Compared with control group,PaO2 was significantly lower in ALI,ALIS and ALIP groups〔mmHg(1 mmHg=0.133 kPa):68±7,82±8,93±7 vs. 116±7〕,and the PaCO2 in ALI and ALIS groups was obviously higher(mmHg:53±6,51±5 vs. 43±7,both P<0.05);lung W/D ratio as well as levels of TNF-α, IL-6 and IL-10 in BALF were significantly higher in ALI,ALIS and ALIP groups〔lung W/D ratio:5.11±0.32, 4.71±0.38,4.53±0.45 vs. 4.48±0.15,TNF-α(ng/L):548±82,431±64,347±53 vs. 162±16,IL-6(ng/L):772±119,587±178,490±139 vs. 127±16,IL-10(ng/L):211±43,295±36,352±59 vs. 104±31,all P<0.05〕. Compared with ALI group,PaO2 in ALIS and ALIP groups was significantly higher,and in ALIP group,PaCO2 was lower,lung W/D ratio,TNF-α and IL-6 in BALF were obviously lower,while IL-10 in BALF was obviously higher(all P<0.05). Compared with ALIS group,the changes in ALIP group were more significant(all P<0.05). Compared with ALIS group,under light microscope,it was shown that the hyper-inflated areas were less,normal and collapsed areas were greater on the ventral side,and the collapsed area was less and the normal ventilation area was greater on the dorsal side in ALIP group(all P<0.05). Conclusion In rats with LPS-induced extra pulmonary ALI,the prone ventilation can improve gas exchange,promote uniform distribution of ventilation,decrease pulmonary edema and in the mean time attenuate inflammatory response.

Effects of electroacupuncture on implementation of nasojejunal tube placement and enteral nutrition in neurosurgical patients in intensive care unit / 中华物理医学与康复杂志

Objective To investigate the effects of electroacupuncture (EA) on the implementation of blind nasojejunal (NJ) tube placement and enteral nutrition (EN) in neurosurgical severe coma patients in intensive care unit (ICU).Methods Seventy-nine neurosurgical severe coma patients admitted to ICU were randomly divided into conventional group (blind NJ tube placement,n =40) and EA group (NJ placement and EA,n =39).EA was performed after NJ tube placement at bilateral acupoints Zusanli (ST36) and Hegu (L14) points using EA treatment instrument.The impelling distance of NJ tube were measured and the success rate of NJ tube placement were calculated.The postoperative complications were observed.Results The difference of NJ tube impelling distances at the 24th,48th,and 72th hours after surgery in EA group were significant longer than that in conventional group (P ＜ 0.05).The success rates of NJ tube placement at the 24th and 72nd hours after surgery in EA group were significantly better than that in conventional group (P ＜ 0.05).Their EN calories qualifiedness rate in 72 hours also increased significantly compared with conventional group and the proportion of patients assisted with parenteral nutrition decreased (P ＜0.05).The postoperative complications including alimentary tract hemorrhage,vomiting,and abdominal distension decreased remarkably in EA group compared with conventional group (P ＜ 0.05).Conclusions EA stimulation at acupoints could promote the gastrointestinal peristalsis of neurosurgical severe coma patients and elevate the success rate of blind NJ tube placement,so it is beneficial for the implementation of early enteral nutrition (EEN).