Comparison of prognosis between extracorporeal CPR and conventional CPR for patients in cardiac arrest: a systematic review and meta-analysis.

AIM: Compared to the conventional cardiopulmonary resuscitation (CCPR), potential benefits of extracorporeal cardiopulmonary resuscitation (ECPR) for patients with cardiac arrest (CA) are still controversial. We aimed to determine whether ECPR can improve the prognosis of CA patients compared with CCPR. METHODS: We systematically searched PubMed, EMBASE, and Cochrane Library from database's inception to July 2023 to identify randomized controlled trials (RCTs) or cohort studies that compared ECPR with CCPR in adults (aged ≥ 16 years) with out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA). This meta-analysis was performed using a random-effects model. Two researchers independently reviewed the relevance of the study, extracted data, and evaluated the quality of the included literature. The primary outcome was short-term (from hospital discharge to one month after cardiac arrest) and long-term (≥ 90 days after cardiac arrest) survival with favorable neurological status (defined as cerebral performance category scores 1 or 2). Secondary outcomes included survival at 1 months, 3-6 months, and 1 year after cardiac arrest. RESULTS: The meta-analysis included 3 RCTs and 14 cohort studies involving 167,728 patients. We found that ECPR can significantly improve good neurological prognosis (RR 1.82, 95%CI 1.42-2.34, I2 = 41%) and survival rate (RR 1.51, 95%CI 1.20-1.89, I2 = 62%). In addition, the results showed that ECPR had different effects on favorable neurological status in patients with OHCA (short-term: RR 1.50, 95%CI 0.98- 2.29, I2 = 55%; long-term: RR 1.95, 95% CI 1.06-3.59, I2 = 11%). However, ECPR had significantly better effects on neurological status than CCPR in patients with IHCA (short-term: RR 2.18, 95%CI 1.24- 3.81, I2 = 9%; long-term: RR 2.17, 95% CI 1.19-3.94, I2 = 0%). CONCLUSIONS: This meta-analysis indicated that ECPR had significantly better effects on good neurological prognosis and survival rate than CCPR, especially in patients with IHCA. However, more high-quality studies are needed to explore the role of ECPR in patients with OHCA.

Effects of endovascular and surface cooling on resuscitation in patients with cardiac arrest and a comparison of effectiveness, stability, and safety: a systematic review and meta-analysis.

OBJECTIVES: This study conducted a meta-analysis to assess the effectiveness, stability, and safety of mild therapeutic hypothermia (TH) induced by endovascular cooling (EC) and surface cooling (SC) and its effect on ICU, survival rate, and neurological function integrity in adult CA patients. METHODS: We developed inclusion criteria, intervention protocols, results, and data collection. The results included outcomes during target temperature management as well as ICU stay, survival rate, and neurological functional integrity. The characteristics of the included population and each study were analyzed. RESULTS: Four thousand nine hundred thirteen participants met the inclusion criteria. Those receiving EC had a better cooling efficiency (cooling rates MD = 0.31[0.13, 0.50], p < 0.01; induced cooling times MD = - 90.45[- 167.57, - 13.33], p = 0.02; patients achieving the target temperature RR = 1.60[1.19, 2.15], p < 0.01) and thermal stability during the maintenance phase (maintenance time MD = 2.35[1.22, 3.48], p < 0.01; temperature fluctuation MD = - 0.68[- 1.03, - 0.33], p < 0.01; overcooling RR = 0.33[0.23, 0.49], p < 0.01). There were no differences in ICU survival rate (RR = 1.22[0.98, 1.52], p = 0.07, I2 = 0%) and hospital survival rate (RR = 1.02 [0.96, 1.09], p = 0.46, I2 = 0%), but EC reduced the length of stay in ICU (MD = - 1.83[- 3.45, - 0.21], p = 0.03, I2 = 49%) and improved outcome of favorable neurological function at discharge (RR = 1.15[1.04, 1.28], p < 0.01, I2 = 0%). EC may delay the hypothermia initiation time, and there was no significant difference between the two cooling methods in the time from the start of patients' cardiac arrest to achieve the target temperature (MD = - 46.64[- 175.86, 82.58]). EC was superior to non-ArcticSun in terms of cooling efficiency. Although there was no statistical difference in ICU survival rate, ICU length of stay, and hospitalization survival rate, in comparison to non-ArcticSun, EC improved rates of neurologically intact survival (RR = 1.16 [1.01, 1.35], p = 0.04, I2 = 0%). CONCLUSIONS: Among adult patients receiving cardiopulmonary resuscitation, although there is no significant difference between the two cooling methods in the time from the start of cardiac arrest to achieve the target temperature, the faster cooling rate and more stable cooling process in EC shorten patients' ICU hospitalization time and help more patients obtain good neurological prognosis compared with patients receiving SC. Meanwhile, although EC has no significant difference in patient outcomes compared with ArcticSun, EC has improved rates of neurologically intact survival.

A meta-analysis of the resuscitative effects of mechanical and manual chest compression in out-of-hospital cardiac arrest patients.

OBJECTIVES: To evaluate the resuscitative effects of mechanical and manual chest compression in patients with out-of-hospital cardiac arrest (OHCA). METHODS: All randomized controlled and cohort studies comparing the effects of mechanical compression and manual compression on cardiopulmonary resuscitation in OHCA patients were retrieved from the Cochrane Library, PubMed, EMBASE, and Ovid databases from the date of their establishment to January 14, 2019. The included outcomes were as follows: the return of spontaneous circulation (ROSC) rate, the rate of survival to hospital admission, the rate of survival to hospital discharge, and neurological function. After evaluating the quality of the studies and summarizing the results, RevMan5.3 software was used for the meta-analysis. RESULTS: In total, 15 studies (9 randomized controlled trials and 6 cohort studies) were included. The results of the meta-analysis showed that there were no significant differences in the resuscitative effects of mechanical and manual chest compression in terms of the ROSC rate, the rate of survival to hospital admission and survival to hospital discharge, and neurological function in OHCA patients (ROSC: RCT: OR = 1.12, 95% CI (0.90, 1.39), P = 0.31; cohort study: OR = 1.08, 95% CI (0.85, 1.36), P = 0.54; survival to hospital admission: RCT: OR = 0.95, 95% CI (0.75, 1.20), P = 0.64; cohort study: OR = 0.98 95% CI (0.79, 1.20), P = 0.82; survival to hospital discharge: RCT: OR = 0.87, 95% CI (0.68, 1.10), P = 0.24; cohort study: OR = 0.78, 95% CI (0.53, 1.16), P = 0.22; Cerebral Performance Category (CPC) score: RCT: OR = 0.88, 95% CI (0.64, 1.20), P = 0.41; cohort study: OR = 0.68, 95% CI (0.34, 1.37), P = 0.28). When the mechanical compression group was divided into Lucas and Autopulse subgroups, the Lucas subgroup showed no difference from the manual compression group in ROSC, survival to admission, survival to discharge, and CPC scores; the Autopulse subgroup showed no difference from the manual compression subgroup in ROSC, survival to discharge, and CPC scores. CONCLUSION: There were no significant differences in resuscitative effects between mechanical and manual chest compression in OHCA patients. To ensure the quality of CPR, we suggest that manual chest compression be applied in the early stage of CPR for OHCA patients, while mechanical compression can be used as part of advanced life support in the late stage.

[Protective effect and mechanism of quercetin on acute liver injury induced by diquat poisoning in mice].

OBJECTIVE: To investigate the protective effect of quercetin (QR) on acute liver injury induced by diquat (DQ) poisoning in mice and its mechanism. METHODS: Eighty healthy male C57BL/6 mice with SPF grade were randomly divided into control group, DQ model group, QR treatment group, and QR control group, with 20 mice in each group. The DQ poisoning model was established by a one-time intraperitoneal injection of DQ solution (40 mg/kg); the control and QR control groups received equivalent amounts of distilled water through intraperitoneal injection. Four hours after modeling, the QR treatment group and the QR control group received 0.5 mL QR solution (50 mg/kg) through gavage. Meanwhile, an equivalent amount of distilled water was given orally to the control group and the DQ model group. The treatments above were administered once daily for seven consecutive days. Afterwards, the mice were anesthetized, blood and liver tissues were collected for following tests: changes in the structure of mice liver tissue were observed using transmission electron microscopy; the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected using enzyme linked immunosorbent assay (ELISA); the levels of glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) in liver tissues were measured using the water-soluble tetrazolium-1 (WST-1) method, the thiobarbituric acid (TBA) method, and enzymatic methods, respectively; the protein expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and activated caspase-9 in liver tissues were detected using Western blotting. RESULTS: Severe mitochondrial damage was observed in the liver tissues of mice in the DQ model group using transmission electron microscopy, yet mitochondrial damage in the QR treatment group showed significant alleviation. Compared to the control group, the DQ model group had significantly increased levels of MDA in liver tissue, serum AST, and ALT, yet had significantly decreased levels of GSH and SOD in liver tissue. In comparison to the DQ model group, the QR treatment group exhibited significant reductions in serum levels of ALT and AST, as well as MDA levels in liver tissue [ALT (U/L): 52.60±6.44 vs. 95.70±8.00, AST (U/L): 170.45±19.33 vs. 251.10±13.09, MDA (nmol/mg): 12.63±3.41 vs. 18.04±3.72], and notable increases in GSH and SOD levels in liver tissue [GSH (µmol/mg): 39.49±6.33 vs. 20.26±3.96, SOD (U/mg): 121.40±11.75 vs. 81.67±10.01], all the differences were statistically significant (all P < 0.01). Western blotting results indicated that the protein expressions of Nrf2 and HO-1 in liver tissues of the DQ model group were significantly decreased compared to the control group. On the other hand, the protein expressions of Keap1 and activated caspase-9 were conspicuously higher when compared to the control group. In comparison to the DQ model group, the QR treatment group showed a significant increase in the protein expressions of Nrf2 and HO-1 in liver tissues (Nrf2/ß-actin: 1.17±0.08 vs. 0.92±0.45, HO-1/ß-actin: 1.53±0.17 vs. 0.84±0.09). By contrast, there was a notable decrease in the protein expressions of Keap1 and activated caspase-9 (Keap1/ß-actin: 0.48±0.06 vs. 1.22±0.09, activated caspase-9/ß-actin: 1.17±0.12 vs. 1.59±0.30), the differences were statistically significant (all P < 0.01). CONCLUSIONS: QR may reduce acute liver injury induced by DQ poisoning in mice via activating Keap1/Nrf2 signaling pathway.

Knowledge, attitudes, practices, and self-efficacy of the Chinese public regarding cardiopulmonary resuscitation: an online cross-sectional survey.

Objective: To evaluate the current status of Chinese public's knowledge, attitudes, practices (KAP) and self-efficacy regarding cardiopulmonary resuscitation (CPR), and to analyze the factors that influence KAP and self-efficacy. Methods: An online cross-sectional survey was conducted from February to June 2022 in Mainland China via a self-designed self-filled questionnaire. Potential participants were recruited through WeChat by convenience sampling and snowball sampling methods. Descriptive and quantitative analyses were used for statistical analysis. Results: The survey included 4,450 participants from 31 provinces, autonomous regions, or municipalities across Mainland China, aged 18 or above. The public's average understanding (clear and very clear) of the knowledge regarding CPR was 67.4% (3,000/4,450), with an average proportion of positive attitudes at 96.8% (4,308/4,450). In practice, the average proportion of good practices was 92.8% (4,130/4,450), while the percentage of good self-efficacy averaged at 58.9% (2,621/4,450), only 42.4% (1,885/4,450) of the participants had confidence in the correct use of automated external defibrillator (AED). Pearson correlation analysis showed a significantly positive correlation among knowledge, attitude, practice, and self-efficacy (p < 0.01). Multiple linear regression analysis revealed that several factors have a significant influence on the public's CPR KAP and self-efficacy, including ever having received CPR training (p < 0.001), hearing about AED (p < 0.001), performing CPR on others (p < 0.001), hearing about CPR (p < 0.001), occupation (p < 0.001), personal health status (p < 0.001), education level (p < 0.001), gender (p < 0.001), and encountering someone in need of CPR (p = 0.021). Conclusion: The Chinese public demonstrates good knowledge of CPR, positive attitude, and high willingness to perform CPR. However, there is still room for improvement in the mastery of some professional knowledge points related to CPR and AED. It should be noted that knowledge, attitude, practice, and self-efficacy are interrelated and influence each other. Factors such as prior CPR training, hearing about AED, having performed CPR before, hearing about CPR, occupation, personal health status, education level, gender, and having encountered someone in need of CPR have a significant impact on the public's KAP and self-efficacy.

A typically progressive dissection of the internal carotid artery with recurrent hiccups: A case report with continuous 2-year data recording.

Patients with internal carotid artery dissection (ICAD) usually report headache, neck pain, Horner's syndrome, and ischemic stroke. Because the posterior cranial nerve is involved, some patients may show different forms of posterior cranial nerve paralysis. There have been no reports of patients with ICAD showing repeated hiccups. Here, to help clinicians identify ICAD early and gain a better understanding of the atypical manifestations of the disease, we report an atypical case of recurrent hiccup symptoms caused by ICAD.

[Protective effect of metformin on pulmonary fibrosis caused by paraquat through activating AMP-activated protein kinase pathway].

OBJECTIVE: To observe whether metformin (MET) inhibits transforming growth factor-ß1 (TGF-ß1)/Smad3 signaling pathway by activating adenosine activated protein kinase (AMPK), so as to alleviate the pulmonary fibrosis caused by paraquat (PQ) poisoning in mice. METHODS: Male C57BL/6J mice were randomly divided into the Control group, PQ poisoning model group (PQ group), MET intervention group (PQ+MET group), AMPK agonist group (PQ+AICAR group), and AMPK inhibitor group (PQ+MET+CC group), according to a random number table method. A mouse model of PQ poisoning was established by one-time peritoneal injection of 1 mL PQ solution (20 mg/kg). The Control group was injected with the same volume of normal saline. After 2 hours of modeling, the PQ+MET group was given 2 mL of 200 mg/kg MET solution by gavage, the PQ+AICAR group was given 2 mL of 200 mg/kg AICAR solution by intraperitoneal injection, the PQ+MET+CC group was given 2 mL of 200 mg/kg MET solution by gavage and then 1 mL complex C (CC) solution (20 mg/kg) was intraperitoneally injected, the Control group and PQ group were given 2 mL of normal saline by gavage. The intervention was given once a day for 21 consecutive days. The 21-day survival rate of ten mice in each group was calculated, and the lung tissues of remaining mice were collected at 21 days after modeling. The pathological changes of lung tissues were observed under light microscope after hematoxylin-eosin (HE) staining and Masson staining, and the degree of pulmonary fibrosis was evaluated by Ashcroft score. The content of hydroxyproline in lung tissue and oxidative stress indicators such as malondialdehyde (MDA) and superoxide dismutase (SOD) were detected. The protein expressions of E-cadherin, α-smooth muscle actin (α-SMA), phosphorylated AMPK (p-AMPK), TGF-ß1 and phosphorylated Smad3 (p-Smad3) in lung tissue were detected by Western blotting. RESULTS: Compared with the Control group, the 21 days survival rate was significantly reduced, lung fibrosis and Ashcroft score were significantly increased in PQ group. In addition, the content of hydroxyproline, MDA and the protein expressions of α-SMA, TGF-ß1 and p-Smad3 in lung tissue were significantly increased, while the activity of SOD and the protein expressions of E-cadherin and p-AMPK were significantly decreased in PQ group. Compared with the PQ group, the 21 days survival rates of mice were significantly improved in the PQ+MET group and PQ+AICAR group (70%, 60% vs. 20%, both P < 0.05). The degree of pulmonary fibrosis and the Ashcroft score were significantly reduced (1.50±0.55, 2.00±0.63 vs. 6.67±0.52, both P < 0.05). The content of hydroxyproline and MDA in lung tissue, as well as α-SMA, TGF-ß1 and p-Smad3 protein expressions were significantly reduced [hydroxyproline (mg/L): 2.03±0.11, 3.00±0.85 vs. 4.92±0.65, MDA (kU/g): 2.06±1.48, 2.10±1.80 vs. 4.06±1.33, α-SMA/GAPDH: 0.23±0.06, 0.16±0.06 vs. 1.00±0.09, TGF-ß1/GAPDH: 0.28±0.03, 0.53±0.05 vs. 0.92±0.06 p-Smad3/GAPDH: 0.52±0.04, 0.69±0.06 vs. 1.11±0.10, all P < 0.05], SOD activity and the protein expressions of E-cadherin and p-AMPK were significantly increased [SOD (µmol/g): 39.76±1.35, 33.03±1.28 vs. 20.08±1.79, E-cadherin/GAPDH: 0.91±0.08, 0.72±0.08 vs. 0.26±0.04, p-AMPK/GAPDH: 0.62±0.04, 0.60±0.01 vs. 0.20±0.04, all P < 0.05]. However, these protective effects of MET were inhibited by the addition of AMPK inhibitor CC solution. CONCLUSIONS: MET can effectively alleviate the degree of pulmonary fibrosis in mice poisoned with PQ, and its mechanism may be related to the activation of AMPK and inhibition of TGF-ß1/Smad3 signaling pathway, which can be inhibited by AMPK inhibitor CC.

Therapeutic and adverse effects of adrenaline on patients who suffer out-of-hospital cardiac arrest: a systematic review and meta-analysis.

OBJECTIVE: The efficacy and safety of epinephrine in patients with out-of-hospital cardiac arrest (OHCA) remains controversial. The meta-analysis was used to comprehensively appraise the influence of epinephrine in OHCA patients. METHODS: We searched all randomized controlled and cohort studies published by PubMed, EMBASE, and Cochrane Library from the inception to August 2022 on the prognostic impact of epinephrine on patients with OHCA. Survival to discharge was the primary outcome, while the return of spontaneous circulation (ROSC) and favorable neurological outcome were secondary outcomes. RESULTS: The meta-analysis included 18 studies involving 863,952 patients. OHCA patients with adrenaline had an observably improved chance of ROSC (RR 2.81; 95% CI 2.21-3.57; P = 0.001) in randomized controlled studies, but the difference in survival to discharge (RR 1.27; 95% CI 0.58-2.78; P = 0.55) and favorable neurological outcomes (RR 1.21; 95% CI 0.90-1.62; P = 0.21) between the two groups was not statistically significant. In cohort studies, the rate of ROSC (RR 1.62; 95% CI 1.14-2.30; P = 0.007) increased significantly with the adrenaline group, while survival to discharge (RR 0.73; 95% CI 0.55-0.98; P = 0.03) and favorable cerebral function (RR 0.42; 95% CI 0.30-0.58; P = 0.001) were lower than the non-adrenaline group. CONCLUSION: We found that both the randomized controlled trials (RCTs) and cohort studies showed that adrenaline increased ROSC in OHCA patients. However, they were unable to agree on a long-term prognosis. The cohort studies showed that adrenaline had an adverse effect on the long-term prognosis of OHCA patients (discharge survival rate and good neurological prognosis), but adrenaline had no adverse effect in the RCTs. In addition to the differences in research methods, there are also some potential confounding factors in the included studies. Therefore, more high-quality studies are needed to fully confirm the effect of adrenaline on the long-term results of OHCA.

[Research progress of S-nitrosoglutathione reductase inhibitors in the regulation of cerebral injury after cardiac arrest-cardiopulmonary resuscitation].

The cerebral ischemia-reperfusion injury (CIRI) after the cardiac arrest (CA)-cardiopulmonary resuscitation (CPR) was a complex pathophysiology process. Nitric oxide (NO) is a small molecule that mediates cell signal transduction in vivo and plays an important role in the regulation of brain function during ischemia/reperfusion (I/R). S-nitrosoglutathione reductase (GSNOR) inhibitor can regulate the synthesis and release of NO in vivo and has a protective effect on CIRI. Therefore, early administration of GSNOR to CA-CPR patients could be the main treatment method to improve the prognosis of those patients. A large number of studies have been done to improve the prognosis of CA-CPR in recent years. In order to provide reference for further research on the treatment and brain protection of CIRI after CA-CPR, the article reviewed the main mechanisms of brain injury after CA-CPR, the protective effect and mechanism of NO on cerebral I/R injury, the production and regulation of NO, in vivo, and the protective effect of GSNOR inhibitors on CIRI, especially the research progress of GSNOR inhibitors.

[Research progress on the relationship between diquat poisoning and nuclear factor E2-related factor 2 signaling pathway].

Since the production and use of paraquat was banned in China in 2016, the use of diquat (DQ) has been increasing and the clinical cases of DQ poisoning have also shown an increasing trend every year. The treatment of DQ poisoning is a worldwide medical problem, and there is no specific antidote. Studies have found that oxidative stress, lipid peroxidation, neurotoxicity, reproductive and developmental toxicity play an important role in DQ poisoning. Nuclear factor E2-related factor 2 (Nrf2) can inhibit oxidative stress, lipid peroxidation and inflammation by regulating the protein expression of upstream and downstream signaling molecules. Therefore, the role of Nrf2 signaling pathway in the poisoning and treatment of DQ has become a hot spot of attention for emergency critical care researchers in recent years. This paper reviews the relationship between Nrf2 signal pathway and DQ poisoning, in order to provide a theoretical basis for improving the treatment strategy for DQ poisoning.

Human Amnion-Derived MSCs Alleviate Acute Lung Injury and Hinder Pulmonary Fibrosis Caused by Paraquat in Rats.

Methods: First, the purity of hAD-MSCs was determined by morphological observation and FCM, and the effects on the survival of paraquat-poisoned Sprague-Dawley rats were observed. All rats were randomly divided into three groups, defined as the sham control group (n = 8), model group (n = 15), and hAD-MSC-transplanted group (n = 17). Pneumonocyte damage and inflammatory cell infiltration were investigated in the three groups of rats, untreated control, paraquat only, and paraquat+hAD-MSC transplanted, using H&E staining. Fibrosis was investigated in three groups of rats using Masson's trichrome staining and Sirius red staining. The profibrotic factor TGF-ß1, the composition of fibrotic collagen HYP, and the hAD-MSC-secreted immunosuppressive factor HLA-G5 in serum were investigated in the three groups of rats using ELISA. Furthermore, the distribution of hAD-MSCs was investigated in the three groups of rats using immunohistochemistry and hematoxylin staining. Results: The hAD-MSCs exhibited typical hallmarks of MSCs, improved the state of being and survival of paraquat-poisoned rats, reduced both lung injury and inflammation, and inhibited the progression of pulmonary fibrosis by decreasing the deposition of collagen and the secretion of both TGF-ß1 and HYP. The hAD-MSCs could survive in damaged lungs and secreted appropriate amounts of HLA-G5 into the serum. Conclusion: The obtained results indicate that hAD-MSCs used to treat paraquat-induced lung injury may work through anti-inflammatory and immunosuppressive pathways and the downregulation of profibrotic elements. This study suggests that the transplantation of hAD-MSCs is a promising therapeutic approach for the treatment of paraquat-intoxicated patients.

Effects of Different Hypothermia on the Results of Cardiopulmonary Resuscitation in a Cardiac Arrest Rat Model.

Objective: To investigate the optimal temperature of hypothermia treatment in rats with cardiac arrest caused by ventricular fibrillation (VF) after the return of spontaneous circulation (ROSC). Methods: A total of forty-eight male Sprague-Dawley rats were induced by VF through the guidewire with a maximum of 5 mA current and untreated for 8 min. Cardiopulmonary resuscitation (CPR) was performed for 8 min followed by defibrillation (DF). Resuscitated rats were then randomized into the normothermia (37°C) group, milder (35°C) group, mild (33°C) group, or moderate (28°C) group. Hypothermia was immediately induced with surface cooling. The target temperature was maintained for 4 h before rewarming to 37 ± 0.5°C. Moreover, at the end of the 4 h, a rat in each group was randomly selected to be sacrificed for the cerebral cortex electron microscopy observation (n = 1). The other resuscitated animals were observed for up to 72 h after ROSC (n = 7). Left ventricular ejection fraction (LVEF) and left ventricular end diastolic volume (LVEDV) were measured. Survival time, survival rate, and neurological deficit score (NDS) were recorded for 72 h. Results: During hypothermia, higher LVEF was observed in the hypothermia groups when compared with normothermia group (35°C vs. 37°C, p < 0.05, 33°C and 28°C vs. 37°C, p < 0.01). Among the hypothermia groups, LVEF was higher in the 28°C group than that of 35°C (p < 0.05). However, both the heart rate (HR) (p < 0.01) and LVEDV (28°C vs. 35°C, p < 0.01, 28°C vs. 37°C and 33°C, p < 0.05) were lowest in the 28°C group when compared with the other groups. There were no significant differences of LVEF and LVEDV between the group 35°C and 33°C (p > 0.05). After rewarming, the LVEF of 35°C group was higher than that of group 37°C, 33°C, and 28°C (35°C vs. 37°C and 28°C, p < 0.01, 35°C vs. 33°C, p < 0.05). Group 35°C and 33°C resulted in longer survival (p < 0.01), higher survival rate (p < 0.01), and lower NDS (35°C vs. 37°C and 28°C, p < 0.01, 33°C vs. 37°C and 28°C, p < 0.05) compared with the group 37°C and 28°C. The extent of damage to cerebral cortex cells in group of 35°C and 33°C was lighter than that in group of 37°C and 28°C. The 35°C group spent less time in the process of cooling and rewarming than the group 33°C and 28°C (p < 0.01). Conclusions: An almost equal protective effect of milder hypothermia (35°C) and mild hypothermia (33°C) in cardiac arrest (CA) rats was achieved with more predominant effect than moderate hypothermia (28°C) and normothermia (37°C). More importantly, shorter time spent in cooling and rewarming was required in the 35°C group, indicating its potential clinical application. These findings support the possible use of milder hypothermia (35°C) as a therapeutic agent for postresuscitation.

[Advances in the study of optimum chest compression point for adult cardiopulmonary resuscitation].

Chest compressions are a key component of cardiopulmonary resuscitation (CPR). The determination of the optimal compression point (OCP) in adult CPR is an indispensable critical factor for high quality chest compressions (CCs). At present, the OCP for adult CPR is still controversial, which still needs further research and discussion. To provide theoretical reference for determining the OCP, this paper reviews the research progress of the OCP of adult CPR from the development process of compression point and hemodynamic mechanism, so as to improve the quality of CCs and the outcome of cardiac arrest (CA) patients.

[Progress in the study of pulmonary fibrosis signaling pathways caused by paraquat poisoning].

Paraquat is a quaternary ammonium herbicide, which can be distributed in lung, liver, kidney, heart, brain and other organs through blood circulation, leading to multiple organ failure, especially lung injury. Due to the lack of effective treatment methods and specific antidotes, the prognosis of most patients with paraquat poisoning is very poor. The treatment of paraquat poisoning was a big problem for emergency doctors. Previous studies have found that pulmonary fibrosis caused by paraquat poisoning is closely related to a variety of pathological processes, such as oxidative stress, inflammatory reaction, mitochondrial damage, imbalance of extracellular matrixproduction (ECM) and degradation, which involve the activation or inhibition of various signaling pathways. In recent years, many researchers focused on clarifying the mechanism of paraquat induced pulmonary fibrosis, and some signaling pathways related to paraquat poisoning leading to pulmonary fibrosis have been found. A large number of studies have found that adenosine monophosphate activated protein kinase (AMPK) related signaling pathway, transforming growth factor-ß/Smad (TGF-ß/Smad) signaling pathway, mitogen-activated protein kinase (MAPK) related signaling pathway, Ras homolog gene/Rho associated kinases (Ras/ROCK) and Wnt/ß-catenin signal pathways are closely related to paraquat induced pulmonary fibrosis. In this paper, we reviewed signaling pathways related to paraquat induced pulmonary fibrosis, in order to provide more ideas for the clinical treatment of paraquat induced pulmonary fibrosis.

An interpretable machine learning model based on a quick pre-screening system enables accurate deterioration risk prediction for COVID-19.

A high-performing interpretable model is proposed to predict the risk of deterioration in coronavirus disease 2019 (COVID-19) patients. The model was developed using a cohort of 3028 patients diagnosed with COVID-19 and exhibiting common clinical symptoms that were internally verified (AUC 0.8517, 95% CI 0.8433, 0.8601). A total of 15 high risk factors for deterioration and their approximate warning ranges were identified. This included prothrombin time (PT), prothrombin activity, lactate dehydrogenase, international normalized ratio, heart rate, body-mass index (BMI), D-dimer, creatine kinase, hematocrit, urine specific gravity, magnesium, globulin, activated partial thromboplastin time, lymphocyte count (L%), and platelet count. Four of these indicators (PT, heart rate, BMI, HCT) and comorbidities were selected for a streamlined combination of indicators to produce faster results. The resulting model showed good predictive performance (AUC 0.7941 95% CI 0.7926, 0.8151). A website for quick pre-screening online was also developed as part of the study.

Metformin Activates the Protective Effects of the AMPK Pathway in Acute Lung Injury Caused by Paraquat Poisoning.

OBJECTIVE: To observe whether metformin (MET) plays a protective role in acute lung injury (ALI) induced by paraquat (PQ) poisoning in rats by activating the AMPK/NF-κB signaling pathway. METHODS: PQ exposure was used to construct a rat model of ALI and a model of acute type II alveolar epithelial cell (RLE-6TN) injury, and MET intervention was performed. Rat lung tissue samples were collected to evaluate pathological changes in rat lung tissue, the oxidation index, and inflammatory factors; cell viability was detected by CCK-8 assays, and the protein expression levels of phospho-AMPK and phospho-NF-κBp65 in rat lung tissue and RLE-6TN cells were observed by Western blotting. RESULTS: Compared with the PQ group, the MET treatment group showed significantly (1) reduced lung wet/dry ratio (W/D: 4.67 ± 0.31 vs. 5.45 ± 0.40, P < 0.001), (2) reduced pathological changes in lung tissue, (3) decreased MDA levels (nmol/mg prot: 2.70 ± 0.19 vs. 3.08 ± 0.15, P < 0.001) and increased SOD and GSH-Px activities (U/mg prot: 76.17 ± 5.22 vs. 45.23 ± 6.58, 30.40 ± 2.84 vs. 21.00 ± 3.20; all P < 0.001) in lung tissue homogenate, (4) reduced levels of IL-1ß, IL-6, and TNF-α in lung tissue homogenates (pg/mL: 47.87 ± 5.06 vs. 66.77 ± 6.55; 93.03 ± 7.41 vs. 107.39 ± 9.81; 75.73 ± 6.08 vs. 89.12 ± 8.94; all P < 0.001), (5) increased activity of RLE-6TN cells (%: 0.69 ± 0.09, 0.76 ± 0.06, and 0.58 ± 0.03 vs. 0.50 ± 0.05; all P < 0.05), (6) decreased protein levels of phospho-NF-κBp65 in lung homogenates and RLE-6TN cells (p-NF-κB/NF-κB: 0.47 ± 0.09 vs. 0.81 ± 0.13; 0.26 ± 0.07 vs. 0.79 ± 0.13; all P < 0.01), and (7) upregulated protein expression of phospho-AMPK in lung homogenates and RLE-6TN cells (p-AMPK/AMPK: 0.88 ± 0.05 vs. 0.36 ± 0.12; 0.93 ± 0.03 vs. 0.56 ± 0.15; all P < 0.01). After the addition of the AMPK inhibitor Compound C (Com C), the protein expression levels of phospho-AMPK and phospho-NF-κBp65 returned to baseline. CONCLUSION: MET can effectively alleviate ALI induced by paraquat poisoning and increase the viability of cells exposed to paraquat. The mechanism may be related to the activation of the AMPK/NF-κB pathway, downregulation of inflammatory mediators such as IL-6 and TNF-α, and upregulation of the SOD and GSH-Px oxidation index, and these effects can be inhibited by the AMPK inhibitor Com C.

[Protective effects of rhizoma paridis total saponins on septic rats].

OBJECTIVE: To investigate the protective effect of rhizoma paridis total saponins and its mechanism on septic rats. METHODS: Septic model was reproduced by cecal ligation and puncture (CLP) in Wistar rats. Rhizoma paridis total saponins was administered to observe its protective effects on septic rats. Blood was collected to determine serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta(IL-1 beta)levels at 2, 6, 12, 24 and 48 hours after operation by means of enzyme-linked immunosorbent assay (ELISA). The pathological changes of lung tissue were observed with light microscope at 72 hours after operation. The peritoneal macrophages (PMPhi) in rats were isolated and the release of TNF-alpha and IL-1 beta in PMPhi after exposure to lipopolysaccharide (LPS, 100 microg/L) were measured by ELISA. RESULTS: Mortality in the rhizoma paridis total saponins group was significantly lower than the CLP group (50.0% vs. 85.0%, P < 0.05). The levels of TNF-alpha and IL-1 beta in serum were significantly lower than those of the CLP group at the same time (P < 0.05 or P < 0.01). The degree of inflammatory injury to the lung was much milder than that in the CLP group. In the in vitro experiment, it was shown that rhizoma paridis total saponins in concentrations of 5, 10, 20 and 40 mg/L could inhibit remarkably the release of TNF-alpha and IL-1 beta from LPS-stimulated PMPhi of rats (all P < 0.01). The differences in TNF-alpha levels among the groups showed no statistically significant difference(all P > 0.05). The level of IL-1 beta in 5 mg/L group was significantly higher than that of the 10 mg/L group (P < 0.05), but showed no difference with those of 20 mg/L and 40 mg/L groups (both P > 0.05). CONCLUSION: Rhizoma paridis total saponins can protect the CLP rats by inhibiting the activation of rat PMPhi to release cytokines and ameliorating acute lung injury.

[Effects between chest-compression-only cardiopulmonary resuscitation and standard cardiopulmonary resuscitation for patients with out-of-hospital cardiac arrest: a Meta-analysis].

OBJECTIVE: To comprehensively evaluate and compare the resuscitation efficacy of chest-compression-only cardiopulmonary resuscitation (CCPR) and standard cardiopulmonary resuscitation (SCPR) for patients with out-of-hospital cardiac arrest (OHCA). METHODS: Databases such as PubMed, Embase, Ovid, Cochrane Library, Wanfang, CNKI, VIP, CBM were searched from the date of their foundation to March 2nd 2018, and the studies on the difference of effects between CCPR and SCPR for patients with OHCA were retrieved. The outcomes included the return of spontaneous circulation (ROSC) rate, survival to hospital discharge, neurological function completion rate. Two reviewers independently screened the literature meeting the inclusion criteria, independently collected information and evaluated the literature quality. Meta-analysis was conducted using RevMan 5.3 software, and sensitivity analysis was conducted by selecting model analysis method and removing single research method. Funnel plot was used to evaluate publication bias. RESULTS: A total of 10 cohort studies were included, including 174 163 patients with OHCA, of which 95 157 undergone CCPR and 79 006 undergone SCPR. The scores of the Newcastle-Ottawa scale (NOS) were 8-9, indicating that the quality of the literatures included was high. It was shown by the Meta-analysis that CCPR had the higher rate of survival to hospital discharge [relative risk (RR) = 1.04, 95% confidence interval (95%CI) = 1.00-1.08, P = 0.04] and neurological function completion (RR = 1.11, 95%CI = 1.06-1.17, P < 0.000 1) than SCPR, but there was no significant difference in ROSC rate between the two groups (RR = 1.01, 95%CI = 0.98-1.04, P = 0.52). In the subgroup, there was no statistical significance between CCPR and SCPR in the rate of survival to hospital discharge in cardiac OHCA patients (RR = 1.13, 95%CI = 0.82-1.57, P = 0.45). However, in non-cardiac OHCA group, SCPR showed more benefits than CCPR in improving the rate of survival to hospital discharge (RR = 0.88, 95%CI = 0.80-0.96, P = 0.004). The above analysis results were consistent in the fixed effect model and random effect model, indicating that the results were reliable and stable. It was shown by the funnel plot that most of the studies were left-right inverted funnel type, indicating a low publication bias. However, the bias could not be completely excluded due to the small number of included literatures. CONCLUSIONS: For patients without OHCA etiological classification, CCPR was not less than SCPR in improving ROSC rate, discharge survival rate and good neurological function, and CCPR was more advantageous in learning and the willingness of bystanders to implement. However, when non-cardiogenic OHCA could be identified, SCPR should be recommended when conditions permit.

[Protective effect of 5-aminosalicylic acid on the kidney of paraquat poisoning rats by Nrf2-ARE signal pathway].

OBJECTIVE: To investigate the protective effect of 5-aminosalicylic acid (5-ASA) on renal injury poisoned by paraquat (PQ) in rats and its mechanism. METHODS: Twenty-four healthy clean male Sprague-Dawley (SD) rats were randomly divided into four groups: normal saline (NS) control group, 5-ASA control group, PQ model group and 5-ASA treatment group, with 6 rats in each group. The rat model of PQ poisoning was reproduced by intraperitoneal injection of 2% PQ solution 20 mg/kg, and the same volume of NS was given in NS control group and 5-ASA control group. Two hours later, the rats in 5-ASA control group and 5-ASA treatment group were intragastrically administered with 1 mL 5-ASA (75 mg/kg) for one time after NS or PQ administration, and those in NS control group and PQ model group were administered with 1 mL double distilled water. Behavioral changes were observed in rats. Then the rats were sacrificed at 24 hours after starting of the experiment for cardiac blood harvest which could be used to detect the biomarkers of renal injury and oxidative stress parameters. The kidney tissue was collected, and the hematein-eosin (HE) staining was conducted for observation of pathological changes in renal tissue, and protein expressions of Nrf2 and heme oxygenase-1 (HO-1) were determined by Western Blot. RESULTS: At 30 minutes after PQ poisoning, rats appeared obvious poisoning symptoms and signs. Twenty-four hours after PQ poisoned, hemocoel of glomerular capillary, swelling of renal tubular epithelial cell and serious micronecrosis appeared under the light microscope. Compared with NS control group, blood urea nitrogen (BUN), serum creatinine (SCr), superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT) and glutathione (GSH) levels were significantly abnormal in PQ model group, and Nrf2 and HO-1 protein expressions in renal tissue were increased. After administration of 5-ASA, the morphological changes and pathological damage were mitigated as compared with those of PQ model group, the levels of BUN, SCr and MDA were decreased significantly [BUN (mmol/L): 11.98±1.81 vs. 18.56±2.32, SCr (µmol/L): 30.67±2.31 vs. 43.67±9.02, MDA (µmol/L): 5.28±0.43 vs. 6.81±1.00], and the SOD activity, CAT and GSH contents were significantly increased [SOD (kU/L): 125.49±7.63 vs. 106.76±7.94, CAT (ng/L): 30.68±3.51 vs. 23.05±1.55, GSH (µmol/L): 3.81±0.44 vs. 3.14±0.17], while the protein expressions of Nrf2 and HO-1 were further increased [Nrf2 protein (gray value): 0.76±0.04 vs. 0.52±0.03, HO-1 protein (gray value): 0.56±0.02 vs. 0.31±0.02, all P < 0.05]. Only 5-ASA intervention had no significant effect on behavior, pathology, renal injury markers and oxidative stress parameters, but it could induce the expressions of Nrf2 and HO-1 protein in renal tissue, which were significantly higher than those of NS control group [Nrf2 protein (gray value): 0.78±0.02 vs. 0.41±0.04, HO-1 protein (gray value): 0.51±0.03 vs. 0.23±0.01, both P < 0.01]. CONCLUSIONS: 5-ASA attenuates the damage of acute renal injury (AKI) caused by PQ, which mechanism may be related with the activation of Nrf2-antioxidant response element (ARE) signaling pathway.

[Effect of methylene blue on traumatic shock in rabbits].

OBJECTIVE: To observe the effect of methylene blue (MB) on the changes in plasma nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and visceral pathologic changes in rabbits with traumatic shock. METHODS: Eighteen rabbits were randomly assigned into 3 groups (n=6): sham operation group, traumatic shock with normal saline (NS) resuscitation group (NS group), and traumatic shock with MB resuscitation group (MB group). In NS group and MB group, hemodynamics was monitored, and plasma contents of NO, TNF-alpha and IL-6 were determined before shock, after shock, after resuscitation, and 0.5, 2 and 4 hours after resuscitation. In sham operation control group, hemodynamics monitoring and plasma contents of NO, TNF-alpha and IL-6 were also determined. Tissue samples of the liver and intestine were obtained after experiments for microscopic examination. RESULTS: Compared with NS group, hemodynamics was stable in MB group. The levels of plasma NO in rabbits after traumatic shock were much higher than those of before shock. In NS group, the levels of plasma NO were progressively increased after resuscitation, reaching peak level at 0.5 hour after resuscitation, then decreased thereafter but still remaining higher than those of before shock. But in MB group, the levels of plasma NO after resuscitation were obviously decreased. In sham operation group, the levels of plasma NO showed no significant changes during the whole course. The levels of plasma TNF-alpha and IL-6 in rabbits after traumatic shock were much higher than those of before shock. But after intravenous administration of MB, the levels of plasma TNF-alpha and IL-6 after resuscitation showed no significant difference compared with the baseline levels. In sham operation group, the levels of plasma TNF-alpha and IL-6 showed no significant changes during the entire course. In NS group, the organs showed prominent pathologic changes. But in MB group, less pathologic changes in the organs were milder, and in sham operation group, there was no obvious pathologic changes in the organs. CONCLUSION: NO, TNF-alpha and IL-6 play important roles in the pathologic process of traumatic shock and the administration of MB after resuscitation can decrease the levels of plasma NO, TNF-alpha and IL-6, improve hemodynamics in traumatic shock, and protect the important organs.