Efficacy and safety of sivelestat sodium in patients with sepsis / 中华危重病急救医学

Objective:To investigate the efficacy and safety of sivelestat sodium in patients with sepsis.Methods:The clinical data of 141 adult patients with sepsis admitted to the intensive care unit (ICU) of the First Affiliated Hospital of Zhengzhou University from January 1, 2019 to January 1, 2022 were retrospectively analyzed. The patients were divided into the sivelestat sodium group ( n = 70) and the control group ( n = 71) according to whether they received sivelestat sodium or not. The efficacy indexes included oxygenation index, procalcitonin (PCT), C-reactive protein (CRP), white blood count (WBC), sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) before and after 7 days of treatment, as well as ventilator supporting time, the length of ICU stay, the length of hospital stay and ICU mortality. The safety indicators included platelet count (PLT) and liver and kidney function. Results:There were no significant differences in age, gender, underlying diseases, infection site, basic drugs, etiology, oxygenation index, biochemical indexes, SOFA and APACHE Ⅱ scores between the two groups. Compared with the control group, the oxygenation index in 7 days was significantly increased [mmHg (1 mmHg ≈ 0.133 kPa): 233.5 (181.0, 278.0) vs. 202.0 (153.0, 243.0), P < 0.01], the levels of PCT, CRP, alanine aminotransferase (ALT) and APACHE Ⅱ score were significantly decreased in the sivelestat sodium group [PCT (μg/L): 0.87 (0.41, 1.61) vs. 1.53 (0.56, 5.33), CRP (mg/L): 64.12 (19.61, 150.86) vs. 107.20 (50.30, 173.00), ALT (U/L): 25.0 (15.0, 43.0) vs. 31.0 (20.0, 65.0), APACHE Ⅱ: 14 (11, 18) vs. 16 (13, 21), all P < 0.05]. However, there were no significant differences in SOFA, WBC, serum creatinine (SCr), PLT, total bilirubin (TBil), aspartate aminotransferase (AST) in 7 days between the sivelestat sodium group and the control group [SOFA: 6.5 (5.0, 10.0) vs. 7.0 (5.0, 10.0), WBC (×10 9/L): 10.5 (8.2, 14.7) vs. 10.5 (7.2, 15.2), SCr (μmol/L): 76.0 (50.0, 124.1) vs. 84.0 (59.0, 129.0), PLT (×10 9/L): 127.5 (59.8, 212.3) vs. 121.0 (55.0, 211.0), TBil (μmol/L): 16.8 (10.0, 32.1) vs. 16.6 (8.4, 26.9), AST (U/L): 31.5 (22.0, 62.3) vs. 37.0 (24.0, 63.0), all P > 0.05]. The ventilator supporting time and the length of ICU stay in the sivelestat sodium group were significantly shorter than those in control group [ventilator supporting time (hours): 147.50 (86.83, 220.00) vs. 182.00 (100.00, 360.00), the length of ICU stay (days): 12.5 (9.0, 18.3) vs. 16.0 (11.0, 23.0), both P < 0.05]. However, there were no significant differences in the length of hospital stay and ICU mortality between the sivelestat sodium group and the control group [the length of hospital stay (days): 20.0 (11.0, 27.3) vs. 13.0 (11.0, 21.0), ICU mortality: 17.1% (12/70) vs. 14.1% (10/71), both P > 0.05]. Conclusions:Sivelestat sodium is safe and effective in patients with sepsis. It can improve the oxygenation index and APACHE Ⅱ score, reduce the levels of PCT and CRP, shorten ventilator supporting time and the length of ICU stay. No adverse reactions such as liver and kidney function injury and platelet abnormality are observed.

Chinese consensus guidelines for therapeutic drug monitoring of polymyxin B, endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.

Positive effects of Xuebijing injection on intestinal microbiota and metabolite spectrum in septic rats / 中华危重病急救医学

OBJECTIVE@#To explore the effect of Xuebijing injection on inflammation in sepsis by regulating intestinal microbiota and its metabolites.@*METHODS@#A total of 45 male Sprague-Dawley (SD) rats were randomly divided into Sham operation group (Sham group), cecal ligation and perforation (CLP) induced sepsis group (CLP group), and Xuebijing intervention group (XBJ group, 4 mL/kg Xuebijing injection was injected intraperitoneally at 1 hour after CLP), with 15 rats in each group. The survival of rats was observed at 24 hours after operation and sacrificed. Feces were collected for 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS) analysis.@*RESULTS@#At 24 hours after operation, all rats in the Sham group survived, the mortality of rats in the XBJ group was lower than that in the CLP group [47% (7/15) vs. 60% (9/15), P > 0.05]. Compared with the Sham group, the diversity of gut microbiota in the CLP group decreased, the dominant flora changed, and the abundance of inflammation-related flora increased. Xuebijing improved the changes in gut microbiota caused by sepsis, and α diversity showed an increasing trend (Ace index: 406.0±22.5 vs. 363.2±38.2, Chao1 index: 409.7±21.8 vs. 362.4±42.5, both P > 0.05). Restrictive constrained principal coordinate analysis (cPCoA) showed a high similarity in gut microbiota among the same group of rats. The CLP group was dominated by Bacteroidetes, while the Sham and XBJ groups were dominated by Firmicutes. In addition, compared with the CLP group, Xuebijing treatment increased the abundance of beneficial bacteria in septic rats, such as Verrucomicrobia, Akkermansia and Lactobacillus. LC-MS and orthogonal partial least squares discriminant analysis (OPLS-DA) showed that there were 12 main differential metabolites among the three groups, and there were certain correlations between these metabolites, which were related to amino acid and lipid metabolism. Correlation analysis showed a significant correlation between changes in metabolites and microbial communities.@*CONCLUSIONS@#Xuebijing can improve the survival rate of septic rats, regulate the composition of intestinal flora and related metabolites, which provides a new pathophysiological mechanism for Xuebijing in the treatment of sepsis.

The relationship between the lipid profiles and inflammation in patients with sepsis / 中华危重病急救医学

Objective:To explore the relationship between the changes in the lipid profiles and the intensity of inflammatory response and disease severity in patients with sepsis, in order to find a biomarker that can quickly evaluate the condition and prognosis of sepsis.Methods:A retrospective analysis was performed on 449 patients with sepsis admitted to department of critical care medicine of the First Affiliated Hospital of Zhengzhou University from October 2019 to May 2021, and 355 patients without sepsis hospitalized in the same period served as the control. The general demographic data, blood lipid and other clinical indicators within 24 hours after admission were collected and compared between the two groups. Bivariate correlation study was used to analyze the relationship between blood lipid levels and inflammation indicators and severity of illness in patients with sepsis. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of each blood lipid component on the 28-day mortality of patients with sepsis. According to the results of ROC curve analysis, the blood lipids were divided into two groups with different levels, and the Kaplan-Meier survival curve was used to compare the cumulative survival rates of the two groups without end-point event (the 28-day mortality was the end-point event).Results:Compared with non-septic patients, the levels of plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were significantly lower in patients with sepsis [TC (mmol/L): 2.93±1.33 vs. 4.01±1.14, HDL-C (mmol/L): 0.78±0.47 vs. 1.16±0.40, LDL-C (mmol/L): 1.53±1.00 vs. 2.71±0.98, all P < 0.05]. In patients with sepsis, plasma cholesterol levels were correlated with the degree of inflammation and severity of the disease to varying degrees, but the HDL-C had the strongest correlation with interleukin-6 (IL-6; r = -0.551, P = 0.000), procalcitonin (PCT, r = -0.598, P = 0.000), sequential organ failure assessment (SOFA; r = -0.285, P = 0.000). The ROC curve analysis showed that among all blood lipid components, HDL-C had the highest predictive value for 28-day mortality of sepsis patients, and the area under the ROC curve (AUC) was 0.718, when the best cut-off value was 0.69 mmol/L, the sensitivity and specificity were 67.3% and 65.2% respectively, and the positive predictive value and negative predictive value were 60.6% and 71.5% respectively. According to Kaplan-Meier survival curve analysis, the mortality of sepsis patients with HDL-C ≤ 0.69 mmol/L was significantly higher than the patients with HDL-C > 0.69 mmol/L, and the difference was statistically significant ( P < 0.000 1). In addition, the 28-day mortality [59.73% (135/226) vs. 28.70% (64/223)], the incidence of multiple organ dysfunction [41.15% (93/226) vs. 31.84% (71/223)], the probability of requiring mechanical ventilation and vasoactive drugs [mechanical ventilation: 56.64% (128/226) vs. 46.18% (103/223); vasoactive drugs: 54.42% (123/226) vs. 38.57% (86/223)], the positive rate of microbial culture [45.58% (103/226) vs. 35.43% (79/223)], and the probability of drug-resistant bacteria [19.91% (45/226) vs. 10.31% (23/223)] in the low HDL-C group of sepsis patients were all higher than the high HDL-C group, the differences were statistically significant (all P < 0.05). Conclusions:Plasma cholesterol levels, especially the HDL-C levels, can well reflect the intensity of inflammation and the severity of the disease in patients with sepsis. And the HDL-C levels can be used as a good biomarker for predicting the short-term prognosis of sepsis.

Analysis of the changes in intestinal microecology in the early stage of sepsis rat based on 16S rDNA sequencing / 中华危重病急救医学

Objective:To investigate the changes of intestinal microecology in the early stage of sepsis rat model by 16S rDNA sequencing.Methods:Sixty male Sprague-Dawley (SD) rats were randomly divided into cecal ligation and puncture (CLP) group and sham operation group (Sham group), with 30 rats in each group. In the CLP group, sepsis rat model was reproduced by CLP method; the rats in the Sham group only underwent laparotomy without CLP. At 24 hours after the operation, the intestinal feces and serum samples of 8 rats in each group were collected. The survival rate of the rest rats was observed until the 7th day. The level of serum tumor necrosis factor-α (TNF-α) was detected by enzyme-linked immunosorbent assay (ELISA). Intestinal feces were sequenced by 16S rDNA sequencing technology. The operational taxonomic unit (OTU) data obtained after sequence comparison and clustering was used for α diversity and β diversity analysis, principal coordinate analysis and linear discriminant analysis effect size analysis (LEfSe) to observe the changes of intestinal microecology in early sepsis rats and excavate the marker flora.Results:At 24 hours after the reproduction of the model, the rats in the CLP group showed shortness of breath, scattered hair and other manifestations, and the level of serum TNF-α increased significantly as compared with that in the Sham group (ng/L: 43.95±9.05 vs. 11.08±3.27, P < 0.01). On the 7th day after modeling, the cumulative survival rate of the Sham group was 100%, while that of the CLP group was 31.82%. Diversity analysis showed that there was no significant difference in α diversity parameter between the Sham group and the CLP group (number of species: 520.00±52.15 vs. 492.25±86.61, Chao1 richness estimator: 707.25±65.69 vs. 668.93±96.50, Shannon index: 5.74±0.42 vs. 5.79±0.91, Simpson index: 0.93±0.03 vs. 0.94±0.05, all P > 0.05). However, the β diversity analysis showed that the difference between groups was greater than that within groups whether weighted according to OTU or not (abundance weighted matrix: R = 0.23, P = 0.04; abundance unweighted matrix: R = 0.32, P = 0.01). At the phylum level, the abundance of Proteobacteria and Candidatus_sacchari in the CLP group increased significantly as compared with the Sham group [18.100% (15.271%, 26.665%) vs. 6.974% (2.854%, 9.764%), 0.125% (0.027%, 0.159%)% vs. 0.018% (0.008%, 0.021%), both P < 0.05]. At the genus level, the abundance of opportunistic pathogen including Helicobacter, Ruthenium, Streptococcus, Clostridium ⅩⅧ in the CLP group was significantly higher than that in the Sham group [5.090% (1.812%, 6.598%) vs. 0.083% (0.034%, 0.198%), 0.244% (0.116%, 0.330%) vs. 0.016% (0.008%, 0.029%), 0.006% (0.003%, 0.010%) vs. 0.001% (0%, 0.003%), 0.094% (0.035%, 0.430%) vs. 0.007% (0.003%, 0.030%), all P < 0.05], and the abundance of probiotics such as Alloprevotella and Romboustia was significantly lower than that in the Sham group [7.345% (3.662%, 11.546%) vs. 22.504% (14.403%, 26.928%), 0.113% (0.047%, 0.196%) vs. 1.229% (0.809%, 2.29%), both P < 0.01]. LEfSe analysis showed that the probiotics belonging to Firmicutes were significantly enriched in the Sham group, and Romboustia was the most significantly enriched species. Opportunistic pathogens such as Helicobacter, Streptococcus and Clostridium ⅩⅧ were significantly enriched in the CLP group, Helicobacter_NGSU_ 2015 was the most significantly enriched species. Conclusion:In the early stage of sepsis, the intestinal microbiota structure of rats is significantly changed, which mainly shows that the abundance of Alloprevotella and other probiotics is significantly reduced, while that of Helicobacter and other opportunistic pathogens is significantly increased.

Metabonomics research of gabex mesylate on septic-induced acute lung injury in rats / 中华急诊医学杂志

Objectve:To study the effect of gabexate mesylate (GM) on acute lung injury (ALI) in septic rats based on metabonomics.Methods:Fifty-seven SD rats were randomly(random number) divided into three groups: sham operation group (SC group), cecal ligation puncture induced septic ALI group (CLP group), and intraperitoneal administration of GM at 1 h after CLP (CLP-GM group). Twenty-four h after the experiment, the survival of rats in the SC, CLP and CLP-GM groups was observed, the lung tissue was collected for HE staining to observe the pathological changes, and the plasma was collected for metabonomics detection to analyze the characteristics of metabolites.Results:Compared with the SC group, the infiltration of inflammatory cells in the lung tissue of rats in the CLP groupincreased significantly, and the metabolic profile of plasma changed significantly. However, the pathological and metabonomic characteristics of the CLP-GM group showed that the above changes were reversed after the application of GM. Twelve major differential metabolites were found in plasma. The metabolic pathways involved in the disorder included biosynthesis of phenylalanine, tyrosine and tryptophan, phenylalanine metabolism and sphingolipid metabolism.Conclusions:GM may improve septic ALI by regulating amino acid metabolism, sphingolipid metabolism and other metabolic pathways.

Prognostic value of high density lipoprotein level in patients with streptococcal bloodstream infection / 中华急诊医学杂志

Objective:Investigate the prognostic value of high density lipoprotein (HDL) level in patients with streptococcal bloodstream infection.Methods:A total of 698 patients with streptococcal bloodstream infection admitted to the First Affiliated Hospital of Zhengzhou University from January 2015 to December 2019 were enrolled. Serum lipid and other clinical data of patients with positive blood culture within 48 h were recorded. The patients were followed up by telephone from January to March in 2020, and the end-point events were recorded, which were all-cause death 60 days after the diagnosis of streptococcal bloodstream infection. The patients were divided into two groups according to the levels of HDL: low HDL group (HDL ≤0.84 mmol/L) and high HDL group (HDL > 0.84 mmol/L). Univariate and multivariate Cox regression analysis were used to analyze the 60-day prognostic factors of patients with streptococcus bloodstream infection. The receiver operating characteristic (ROC) curve was used to explore predictive value of HDL level for 60-day prognosis of patients. Kaplan-Meier survival curve was used to compare the cumulative survival of patients with different HDL levels.Results:(1) A total of 491 patients were enrolled according to the inclusion criteria, and 461 patients were followed up successfully, with a follow-up rate of 93.89%. There were 373 survival patients and 88 death patients at 60 days, with a 60-day mortality rate of 19.09% (88/461). (2) There were significant differences in age, total cholesterol (TC), HDL, low density lipoprotein (LDL), platelets, albumin, fibrinogen, triglyceride (TG), creatinine, alanine aminotransferase, aspartate aminotransferase, white blood cell, PCT, total bilirubin, direct bilirubin, and respiratory failure and shock between the survival group and death group. (3) Multivariate Cox regression analysis showed that HDL ( RR=1.922, 95% CI: 1.186-3.117, P=0.008), aspartate aminotransferase ( RR=1.953, 95% CI: 1.233-3.094, P=0.004), shock ( RR=15.196, 95% CI: 6.953-33.211, P< 0.001), and respiratory failure ( RR=9.509, 95% CI: 4.232-21.367, P < 0.001) were independent risk factors for 60-day mortality of patients with streptococcal bloodstream infection. (4) The ROC curve analysis showed that HDL alone had a certain value in predicting the 60-day prognosis of patients with streptococcal bloodstream infection. The area under ROC curve (AUC) was 0.602, and the AUC of the combined predictive value of HDL, aspartate aminotransferase, shock and respiratory failure was 0.960, with a sensitivity of 92% and a specificity of 92%. (5) Kaplan-Meier survival curve analysis showed that the cumulative survival rate of patients without endpoint event in the HDL > 0.84 mmol/L group was higher than that in the HDL ≤ 0.84 mmol/L group, but without statistically significant difference (Log-Rank test: χ20.843, P<0.358). Conclusions:Patients with low HDL level of streptococcal bloodstream infection have an increased risk of 60-day death. HDL is an independent risk factor for 60-day death in patients with streptococcal bloodstream infection, and can be used as an indicator to evaluate the prognosis of patients with streptococcal bloodstream infection.

The role of KLF4 in LPS induced cardiomyocyte injury / 中华急诊医学杂志

Objective:To investigate the role of KLF4 in lipopolysaccharide induced cardiomyocyte injury.Methods:Primary rat cardiomyocytes were isolated and cultured, and randomly divided into 5 groups: control group, negative control (NC), LPS group, KLF4 overexpression group, KLF4 overexpression+LPS group. MTT method was used to detect cell activity, ROS, SOD 2, GPX and MDA were detected by kit, TNFa, IL-1 β and IL-6 were detected by ELISA. TUNEL staining was used to detect apoptosis. The protein levels of TLR4 and Nrf2 were detected by Western blot.Results:The expression of KLF4 in cardiomyocytes was significantly higher than that in the NC group ( P<0.001). The cell activity of LPS group was significantly lower than that of NC group ( P < 0.001), and that of KLF4 overexpression +LPS group was higher than that of LPS group ( P<0.001). The levels of TNFa, IL-1 β and IL-6 in LPS group were significantly higher than those in the NC group ( P<0.0001), and the levels of TNFa, IL-1 β and IL-6 in KLF4 overexpression +LPS group were lower than those in LPS group ( P<0.0001). The levels of ROS and MDA in LPS group were significantly higher than those in the control group, while the activities of SOD2 and GPX were lower than those in the NC group ( P<0.0001); the levels of ROS and MDA in KLF4 overexpression +LPS group were lower than those in LPS group, while the activities of SOD2 and GPX were higher than those in LPS group ( P<0.0001). The number of apoptosis in LPS group was significantly higher than that in the NC group, and that in KLF4 overexpression +LPS group was lower than that in LPS group ( P< 0.001). The level of TLR4 wan higher and Nrf2 protein in the nucleus of LPS group was lower than that of the NC group. The level of TLR4 was lower and Nrf2 protein in the nucleus of KLF4 overexpression+LPS group was significantly higher than that of LPS group ( P < 0.001). Conclusions:KLF4 can alleviate LPS induced cardiomyocyte injury by regulating TLR4 and NRF2 signals.

Evidence-based nursing expert consensus on adult bedside ultrasound / 中华危重病急救医学

Bedside ultrasound plays an important role in the evaluation of critically ill patients. In order to standardize the application of bedside ultrasound, Chinese Research Hospital Association of Critical Care Medicine and Nursing Research Group of Chinese Research Hospital Association of Critical Care Medicine organized the experts in related fields in China to analyze, discuss and summarize the following contents: ① bedside ultrasound assessment of lungs; ② bedside ultrasound -guided nutrition tube placement; ③ bedside ultrasound assessment of gastric residual volume; ④ bedside ultrasound -guided endovascular catheterization. Finally, the Evidence-based nursing expert consensus on adult bedside ultrasound was formulated.

Nationwide survey on clinical treatment of coronavirus disease 2019 in 9 provinces and municipalities / 中华危重病急救医学

Objective:To investigate the clinical treatment and assess the knowledge and use of the coronavirus disease 2019 (COVID-19) treatment plan issued by the nation.Methods:A nationwide questionnaire survey on line was administered to medical staffs involved in COVID-19 treatment on February 28th, 2020. The questionnaire included drug treatment, respiratory support therapy, sedation and analgesia, continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO), etc.Results:There were 1 103 respondents, of whom 699 (504 doctors and 195 nurses) participated in the treatment of COVID-19. Finally, 432 doctors and 170 nurses from 9 provinces submitted valid questionnaires. The results of the questionnaire surveys of doctors and nurses were basically the same. Considering that doctors dominated in the diagnosis and treatment of COVID-19, the results of the questionnaires of doctors were mainly analyzed. The doctors participating in the survey were mainly from Hubei (29.2%), followed by Henan (24.5%), Guizhou (22.7%), and Guangxi (14.6%), etc. 55.4% of the doctors came from tertiary three hospitals, and most of them have senior titles (56.4%). 232 doctors (53.7%) participated in the treatment of mild COVID-19, and 200 doctors (46.3%) participated in the treatment of severe and critically ill patients. More than 95% of the doctors expressed that they would carry out antiviral treatment for patients with COVID-19 regardless of disease severity. The main antiviral drugs included α-interferon (69.5%), lopinavir/ritonavir (65.0%), abidol (60.0%), and ribavirin (55.7%). The choice of antiviral drugs was highly consistent with the national treatment programs of COVID-19. At the same time, 95.5% of doctors would routinely prescribe antibiotics to severe and critically ill patients. 94.0% of doctors agreed to prescribe low-dose glucocorticoid therapy to severe and critically ill patients. About 2/3 of doctors would perform lung recruitment or prone position treatment for critical patients with invasive ventilation. 79.0% of doctors preferred to use deep sedation for patients with invasive ventilation. About 1/3 of doctors believed that CRRT should be initiated early, and nearly 1/3 of doctors suggested that ECMO should be used more aggressively in critically ill patients.Conclusions:Medical staffs are familiar with the national treatment plan of COVID-19 and willing to follow it. However, as a new disease, we have limited knowledge about COVID-19 and there are still many controversies. Further practical training is needed to make clinicians more aware of the disease, and more evidence-based evidence is needed to guide clinical treatment.

Value of serum cholinesterase in the prognosis of septic shock / 中华危重病急救医学

Objective:To investigate the relationship between serum cholinesterase (SChE) level and the prognosis of patients with septic shock (SS).Methods:A total of 594 patients with SS admitted to the First Affiliated Hospital of Zhengzhou University from June 2013 to June 2017 were enrolled. General data such as gender, age, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score were recorded as well as routine blood test, procalcitonin (PCT), hepatic function, renal function, coagulation function and blood gas analysis parameters within 48 hours of SS diagnosis. The patients were followed by telephone from September to October in 2019, and the outcome was recorded. The primary outcome was all-cause death 28 days after discharge. The secondary outcomes were all-cause death in intensive care unit (ICU) and 2 years after discharge, and the length of ICU stay. The patients were divided into two groups according to prognosis of 28 days: the survival group and the death group. The clinical data of the two groups were compared. Multivariate Cox regression analysis was used to screen prognostic risk factors of 28 days in patients with SS. The receiver operating characteristic (ROC) curve was used to explore predictive value of liver function parameter SChE for 28-day prognosis of patients with SS. The patients were divided into two groups according to the levels of SChE: the low SChE group (SChE ≤ 4 000 U/L) and the normal SChE group (SChE > 4 000 U/L). Kaplan-Meier survival curves were used to compare the cumulative survival rates without endpoint event of patients with different SChE levels.Results:A total of 385 patients with SS were enrolled according to the inclusion and exclusion criteria, and a total of 356 patients were followed up successfully, with a follow-up rate of 92.5% (356/385). There were 142 survival patients and 214 death patients at 28 days, with a 28-day mortality rate of 60.1% (214/356). There were 116 survival patients and 240 death patients at 2 years, with a 2-year mortality rate of 67.4% (240/356). Compared with the 28-day survival group, the patients in the death group were older and had higher APACHEⅡ score, partial hepatic and renal function parameters, higher level of blood lactate (Lac) and lower levels of white blood cell count (WBC), platelet count (PLT) and SChE with statistically significant differences. Multivariate Cox regression analysis showed that the age [relative risk ( RR) = 1.444, 95% confidence interval (95% CI) was 1.090-1.914, P = 0.010], APACHEⅡ score ( RR = 2.249, 95% CI was 1.688-2.997, P = 0.000), SChE ( RR = 1.469, 95% CI was 1.057-2.043, P = 0.022), and Lac ( RR = 2.190, 95% CI was 1.636-2.931, P = 0.000) were independent risk factors for 28-day mortality of patients with SS. The ROC curve analysis showed that SChE had a weak prognostic value for 28-day prognosis of patients with SS [the area under ROC curve (AUC) was 0.574]. However, the combined predictive value of SChE, APACHEⅡ score and Lac was greater than APACHEⅡ score or Lac alone for prediction (AUC: 0.807 vs. 0.785, 0.697), with a sensitivity of 79.9% and a specificity of 68.5%. Compared with the normal SChE group ( n = 88), the 28-day mortality of patients in the low SChE group ( n = 268) was significantly increased [63.1% (169/268) vs. 51.1% (45/88), P < 0.05], but ICU mortality [59.7% (160/268) vs. 48.9% (43/88)], 2-year mortality [69.8% (187/268) vs. 60.2% (53/88)] or the length of ICU stay [days: 4 (2, 7) vs. 5 (2, 9)] between the two groups showed no statistical significance (all P > 0.05). Kaplan-Meier survival curve analysis showed that the cumulative survival rate without endpoint event of patients in the low SChE group was significantly lower than that in the normal SChE group (Log-Rank test: χ 2 = 5.852, P = 0.016). Conclusions:Increased risk of 28-day mortality in patients with SS whose SChE is below normal. The level of SChE is an independent risk factor for 28-day death in SS patients, and it is one of the indicators to evaluate the short-term prognosis of patients with SS.

A report on the follow-up of 14 patients with familial thallium poisoning after 9 years / 中华急诊医学杂志

Objective:To investigate the recovery of patients with acute thallium poisoning after 9 years.Methods:A group of 14 patients with familial thallium poisoning who were admitted to our hospital in 2010 were followed up for 9 years.Results:Among the 14 patients with acute thallium poisoning, one patient died on the 14th day after poisoning, and all the other survivors were followed up 9 years later. The general condition of all the patients was significantly better than that of poisoning 9 years ago. The alopecia of all cases disappeared, the newborn hair grew normally, without gastrointestinal symptoms, numbness, pain in the limbs and mental symptoms. All the patients returned to normal intelligence and physical strength and had a normal life. One patient (No. 5) gave birth to 2 children successively after discharge. The first child was 6 years old and the second child was 2 years old. Both growth and intelligence were not different from those of the same age. Currently, the third pregnancy was more than 7 months. No.6 and No.10 patients were poisoned in their teenage and were currently all studying in university. No.6 patient suffered from Hashimoto's thyroiditis 7 years after poisoning, and he has been taking thiamazole tablets for two years. Poisoned infants, No.7, 8 ,11 and 12, were school-age children with normal growth, mental development and excellent academic performance. Among the 13 surviving patients, blood and urine samples from No. 1, No. 3, and No. 4 patients were collected, and no thallium concentration was detected, and biochemical examina-tion and neurological examination were all normal.Conclusions:Patients with acute thallium poisoning have a favorable prognosis according to the follow-up after 9 years. All patients have no obvious sequelae and have normal labor ability. Young women have normal fertility, and children have normal growth and mental development.

Seven years of painstaking efforts, strive to create the future: rapidly developed genernal intensive care unit of the First Affiliated Hospital of Zhengzhou University / 中华危重病急救医学

On?November?11,?2011,?under?the?development?concept?of?"becoming?bigger?and?stronger",?the?general?intensive?care?unit?(GICU)?of?the?First?Affiliated?Hospital?of?Zhengzhou?University?was?established?and?the?first?critically?ill?patient?was?admitted.?With?the?support?of?national?policy,?and?the?guidance?of?the?strategic?goal?of?"being?more?careful?and?more?superior,?and?pursuing?high?quality?and?sustainable?development",?GICU?has?developed?well.?By?2018,?there?are?two?wards?in?the?Heyi?district?and?Zhengdong?district,?which?consist?of?73?beds,?and?more?than?5?000?critically?ill?patients?are?admitted?to?GICU?annually.?Since?the?establishment?of?GICU?for?7?years,?we?have?published?more?than?70?academic?papers,?received?two?national?natural?science?funds?support,?and?won?the?second?prizes?of?scientific?and?technological?progress?in?Henan?Province?two?times.

Randomized controlled study of immune nutrition in patients with acute stress / 中华急诊医学杂志

Objective To explore the effects of immune-enhanced enteral nutrition support on the clinical outcome and nutritional status of patients with acute stress.Methods From December 2014 to August 2015,120 patients with acute stress were enrolled in this study in the First Affiliated Hospital of Zhengzhou University.The patients were randomly divided into the control group and the experimental group,60 cases in each group.Besides of medical treatment,the control group received routine enteral nutrition,while the experimental group received immune-enhanced nutrition for 8 days.The main parameters related to nutritional status,immune function,blood glucose,infection control of patients were collected.Results No significance of parameters listed above were observed between patients in the two groups at baseline.After intervention,the levels of prealbumin and lymphocyte counts in the experimental group were higher than those in the control group [(162.5±29.7) mg/L and (136.6±15.1) mg/ L,(1.86±0.9) × 109/L and (1.45±0.710) × 109/L,P=0.021 and P=0.012].The levels of C-reactive protein in the experimental group were lower than those in the control group [(47.2±22.1) mg/L and (82.6±13.4) mg/L,P--0.043].Moreover,the level of blood glucose in the experimental group was lower than that in the control group [(5.4±1.7) mmol/L and (6.6±3.5) mmol/L,P=0.009].The patients in the experimental group had better intestinal tolerance (8.3％ vs 25％,P=0.014) but lower mortality (6.7％ vs 20％,P=0.032) than those in the control group.Conclusions Immune-enhanced enteral nutrition can reduce level of blood glucose and alleviate inflammatory responses of patients with acute stress,thus improving intestinal tolerance,and reducing mortality.

The neural function repair and mechanism of (-)-epicatechin on murine traumatic brain injury / 中华急诊医学杂志

Objective To investigate whether (-)-epicatechin plays a role in neurological repair on traumatic brain injury in mice.Methods The mice model of traumatic brain injury was established by modified weight drop method.Experimental mice were randomly (random number) divided into the injury+ (Veh) group and the injury + (-)-epicatechin (EC) group.At 3 days after operation,the expression of IL-1β and TNF-α were detected.The number of necrotic cells of the lesion area was detected by PI staining.At 28 days after SCI,Morris Water Maze test was performed to observe the ability of spatial learning and memory in mice.The expression of neurotrophic factors BDNF and NGF were examined by qRT-PCR.The expression of NeuN was detected by immunofluorescence staining.EdU staining was used to observe the neurogenesis in the SGZ region.Results Compared with the Veh group,EC treated group showed better spatial learning and memory ability in time spent in correct quadrant at day 27 and 28 [24 d:(26.333±5.037)％ vs (26.583±5.802)％,P=0.938;25 d (33.300±4.724)％ vs (29.767±3.347)％.P=0.166;26 d:(41.017±7.246)％ vs (32.800±8.145)％,P=0.095;27 d:(48.017±7.424)％ vs (35.267±6.748)％,P=0.011;28 d:(51.617±9.017)％ vs (41.116±6.467)％,P=0.043] and in latency to platform at day 27 and 28 [24 d:(62.967±5.494) s vs (63.917±7.027) s,P=0.800;25 d:(50.533±10.305) s vs (57.217±13.085) s,P=0.349;26 d:(40.333± 10.526) s vs (50.133±11.039) s,P=0.147;27 d:(28.717±4.137) s vs (44.533±7.181) s,P=0.001;28 d:(21.950±6.889) s vs (37.567±5.974) s,P=0.002].There was a decreased expression of IL-lβ and TNF-α and increased level of neurotrophic factor BDNF and NGF after EC treatment in EC treatment group,compared to the veh treatment group [IL-1β and TNF-α:(42.690±3.057) ng/mL and (750.167±51.941) ng/mL vs (71.670±4.996) ng/mL and (1 085.167±68.535) ng/mL,P=0.000 6 and 0.003;BDNF and NGF:0.543±0.033 and 0.334±0.041 vs 0.756±0.088 and 0.514±0.047,P=0.048 and 0.017)].EC decreased the cell death near injury area (54.833±5.486 vs 74.000±5.323,P=0.031),increased NeuN positive cells (76.667±6.386 vs 42.167±5.237,P=0.002),and increased neurogenesis in SGZ area (12.667±0.760 vs 7.500±1.258,P=0.031).Conclusions (-)-Epicatechin plays an important role in functional recovery after traumatic brain injury in mice.The underlying mechanisms are closely related to inhibited inflammation,enhanced neurotrophic factors and improved neurogenesis.

The effect of adipose-derived stem cells on the lung colonization, TNF-α and IL-4 in rats with LPS-induced acute lung injury / 中华急诊医学杂志

Objective To explore the effect of 5-ethynyl-2'-deoxyuridine (EdU) -labeled adipose-derived stem cells (ADSCs) on lung colonization, TNF-α and IL-4 in rats induced by lipopolysaccharide (LPS) with acute lung injury. Methods Thirty male Sprague-Dawley (SD) rats were randomly divided into the normal control group (n=10), LPS model group (n=10), and LPS+ADSCs intervention group (n=10). The ALI model rats were intraperitoneally injected with 8 mg/kg LPS, rats in the normal control group were intraperitoneally injected with 4 mL/kg physiological saline, and rats in the LPS+ADSCs group were intravenously injected with 300 μL ADSCs by tail vein after 30 minutes for the ALI model establishment, and rats in the normal control group and LPS group were intravenously injected with 300μL physiological saline by tail vein. The time of death in rats was observed, lung tissue and blood from left ventricular were collected, and the serum tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-4) were detected by Enzyme-linked immunosorbent assay (ELISA). Lung wet/dry weight (W/D) ratio was detected by thoracotomy, the pathological changes of lung tissue were observed under optical microscope, and the colonization of ADSCs in the lungs were observed under immunofluorescence microscopy. LSD-t method was used to compare between every two groups. Results There was no significant difference in mortality between the LPS group and LPS + ADSCs group (50％ vs. 70％, P> 0.05); EdU-labeled ADSCs were extensively colonized in the lungs by tail vein injection after 24 h; Compared with the normal control group, the lung injury of the LPS group was heavier, the ratio of lung W/D and TNF-α were significantly increased (all P< 0.01), and IL-4 level was significantly decreased (P< 0.01). Compared with the LPS model group, the degree of lung injury in the LPS + ADSCs group was significantly reduced, lung W/D ratio (5.57±0.27 vs. 5.98±0.28) and TNF-α level of blood [(41.51±4.14)ng/L vs. (45.52±3.74)ng/L] were significantly reduced (all P< 0.05), whereas the IL-4 levels were significantly increased [(7.01±1.11)pg/mL vs. (3.27±0.54)pg/mL, P< 0.05]. Conclusions EdU-labeled ADSCs could be colonized in the lungs of LPS-induced ALI rats, reduce the inflammatory response from TNF-α and improve the anti-inflammatory response from IL-4.

Transplantation of Wharton's jelly alleviates inflammatory response and depression after traumatic brain injury in mice / 中华急诊医学杂志

Objective To investigate the influence of Wharton's jelly (W J) transplant on brain inflammation and mood status in traumatic brain injury (TBI) mouse model.Methods The WJ was isolated from human umbilical cord and cultured,and the cell phenotype of P3 human umbilical cord mesenchymal stem cells was identified by flow cytometry.The animal model was established by modified weight drop method.Experimental mice were randomly(random number) divided into Veh(normal saline)and WJ transplantation groups.After 3 days,water content of damaged brain was detected.Elisa kit was used to detect the expression of IL-1β and TNF-αt.The expression of GFAP,Ibal and CD68 were detected by immunofluorescence.Het(hydroethidine) staining was used to detect reactive oxygen species (ROS) production.Neurologic deficit score was used to evaluate the motor function,sucrose preference test,tail suspension test and forced swim test were used to detect the depression of mice.The data were expressed in ((-x)±s) and analysed by SPSS 21.0 software.Two-way ANOVA with repeated measures design was used to compare difference bewteen two groups at multiple interval.Results Compared with Veh group,the mice in the WJ group had a better performance in NDS scored test(d 1:14.8± 1.169 vs.15.2+ 1.472);3d:(11.0±1.414 vs.13.5+1.225);7d:(9.5±1.517 vs.12.0±1.549);14d:(7.7±0.816 vs.10.5±1.643);21d:(6.5±0.547 vs.9.0±1.265);28d:(5.3+0.816 vs.7.8±1.169),P＜0.05].After TBI,WJ tissue transplantation increased sucrose preference index from (54.49±1.505)％ to (64.56±2.279)％ (P=0.004),decreased immobility time using tail suspension test from (144.7±5.493)s to (115.7±4.660)s (P＜0.01),and decreased immobility time using forced swim test from (260.3±4.558)s to (215.8±5.003)s (P=0.002).After WJ transplantation,brain water content was reduced from (84.48±1.802)％ to (75.58+1.559)％ (P=0.004),the expression of IL-1β and TNF-α near injury area also decreased(P=0.000 6 and 0.000 3),as well as the expression of ROS(P=0.020).The fluorescence intensity of activated astrocytes decreased from (2 906±431.591)to (165 8±312.912) (P=0.041),and the number of microglias and activated microglias were both reduced(P=0.049 and P＜0.01) after TBI.Conclusions Wharton's jelly alleviated the inflammation and depression in traumatic brain injured mice.

The role of terlipressin in treatment of septic shock: a single center randomized controlled double-blind clinical trial / 中华急诊医学杂志

Objective To evaluate the efficacy and safety of terlipressin for septic shock.Methods A randomized double-blind placebo-controlled pilot study was carried out in the general ICU of the First Affiliated Hospital of Zhengzhou University from June 1st 2015 to May 31st 2016.The septic shock patients with a mean arterial pressure below 65 mmHg despite adequate volume resuscitation were enrolled.Patients were randomized (random number) to give continuous infusions of either terlipressin[0.6-2.6 μg/(kg·h)] or norepinephrine(7-30 μg/min).Open label norepinephrine or other catecholamines were additionally infused if the mean arterial pressure failed to reach 65 mmHg.Treatment was continued until shock corrected,death or withdrawn from this study.Correcting rate of shock was the primary end point,the secondary end points included open labeled norepinephrine requirements,the 28 d survival rate and adverse events.The quantitative data of the two groups were compared by t test or Wilcoxon rank sum test.The enumeration data were compared by chi square test or Fisher exact probability method,and the survival data were analyzed by Kaplan-Meier method.Results A total of 28 patients were enrolled.The full analysis set was 28,the per-protocol set was 25,and the safety set was 28.The key demographics and baseline characteristics were similar between the two groups(P＞0.05).The results for the per-protocol set were followed up.The correcting rate of shock between the two groups were similar at the end of treatment[81.82％(9/11)vs.57.14％(8/14),P=0.190].The open label norepinephrine requirements of the trial group and control group for the 0,6,12,24,48 h time point were 0.661,0.921,1.583,1.241,2.143,1.371,1.071,1.261,0.370,1.001 μg/(kg·min),respectively with no significant difference(P＞0.05).The 28 d survival rate of the trial group and control group were 63.64％(7/11)and 50.00％(7/14) respectively with no statistical significance(P＞0.05).There was no significant difference in 28 d survival analyzed using Kaplan-Meier plot between two groups(P=0.470).There were two patients with ischemia of fingers,one patient with hyponatraemia and one patient with ischemia of intestine accompanied by hyponatraemia occurred after treatment with terlipressin,and one patient with isehemia of fingers occurred after treatment with norepinephrine.The incidence of adverse event for the trial group and control group were 30.77％(4/13) and 6.67％(1/15) with no significant difference(P=0.122).Conclusions Terlipressin is an effective agent for treating septic shock.The total adverse event rate of terlipressin was similar to that ofnorepinephrine.

Evaluation of the effectiveness of comprehensive hypertension management in Zhengzhou / 中华健康管理学杂志

Objective To evaluate the effectiveness of a comprehensive hypertension management. Methods Hypertensive patients aged≥35 years in the Zhengfei community of Zhengzhou were selected. The patients were randomly assigned to the intervention and control groups. Those in intervention group received comprehensive hypertension management from October 2015 to September 2016,whereas those in the control group received the original management mode. Scales to assess blood pressure control, biochemical indexes, unhealthy lifestyle, and cardiovascular disease associated risk level were used to evaluate the effectiveness of the management modes.Results Each study groups had 1 051 patients.There were no significant differences in the baseline data of the two groups (P>0.05). At the end of 1 year of receiving the respective hypertension management modes, each group had 941 patients. Findings revealed that after receiving the comprehensive hypertension management mode, the systolic and diastolic blood pressure in the intervention group decreased by(9.87±7.38)mmHg(1 mmHg=0.133 kPa)and(6.33±4.14) mmHg,respectively.Those in the control group decreased by(7.01±6.02)mmHg and(4.52±3.59)mmHg, respectively,statistically significant differences in the extent of reduction of blood pressure between the two groups (P<0.05). Further, the fasting plasma glucose, postprandial blood glucose, low density lipoprotein, serum creatinine,and microalbuminuria levels in the intervention group were significantly lower than those in the control group(all P<0.05).However,the intervention group exhibited a significant increase in the high density lipoprotein level as compared to the control group(P<0.05).There were no significant differences in the total cholesterol,triglyceride,urinary creatinine levels,and body mass index between the two groups(P>0.05), although they had decreased in both groups. After the 1-year management, these proportions of smoking,heavy drinking,high salt diet and need to exercise were 10.0%,3.7%,20.1%,and 48.9% in the intervention group, and 15.3%, 10.0%, 29.0%, and 54.3% in the control group. The proportions were significantly different between the two groups (P<0.05). After the 1-year management, these proportions of low,moderate,and high risk of cardiovascular disease were 13.3%,33.5%,and 53.2% in the intervention group, and 11.2%, 30.1%, and 58.8% in the control group, respectively, with statistically significant differences between the two groups (P< 0.05). After the 1-year management, the proportion of treated, controlled, and control-treated hypertension using medication was 100%, 65.1%, and 75.3% in the intervention group, and 39.5%, 60.3%, and 70.0% in the control group, respectively, with statistically significant differences between the two groups (P< 0.05). Conclusion The comprehensive hypertension management mode was effective in significantly improving the blood pressure and health condition of hypertensive patients.

The early diagnosis value of electrocardiographic characteristics in acute embolism in the pulmonary trunk and the main pulmonary arteries / 中华急诊医学杂志

Objective To investigate the abnormal characteristics of electrocardiogram and its early diagnostic value in acute pulmonary embolism (PE) of different positions.Methods A total of 147 hospitalized patients of acute PE diagnosed by the pulmonary artery CT angiography (CTA) were enrolled in this study and divided into the following two groups:pulmonary trunk or main pulmonary artery (MPA) embolism (group A) and lobar artery or remote branch embolism (group B).ECG,D-dimer,BNP,cTnT were collected and determined,the varieties of abnormal ECG were counted.Then,the relationships between the severities of the PEs at different positions and the corresponding ECG abnormalities as well as the degree of right ventricular hypertrophy (RVH) were analyzed.Results There were significant differences in dyspnea,syncope,in-hospital mortality and the level of cTnT,BNP between the two groups (P ＜ 0.05).There were significant differences in the occurrence of SIQ Ⅲ T Ⅲ,right bundle branch block (RBBB),ST segment depression (STD) in leads Ⅲ and aVF,ST segment elevation (STE) in lead aVR,negative T waves (NTWs) in leads Ⅲ and aVF,STD in leads V1-V3/V6,and STE in leads V1-V3 in combination with STD in leads V4-V6 between the two groups (P ＜ 0.05).The proportion of RVH diagnosed via ECG has significantly different between the two groups.The result of correlation analysis showed that the incidence of pulmonary trunk or MPA embolism was significantly related to the number of ECG abnormalities (r =0.782,t =-7.086,P ＜ 0.05).Conclusions The number of abnormal ECGs increase and the RVH is more serious when PE occurring in pulmonary trunk as well as in the MPA,early recognition of electrocardiographic abnormalities is of greater value in the diagnosis of acute pulmonary trunk and MPA embolism.