Cardiac arrest (CA) is an acute critical illness with the high occurrence in the world. The directions of cardiopulmonary resuscitation (CPR) development are to improve CA patients' survival rate and to decrease the poor prognosis. β-blockers can selectively block the neurotransmitter or receptor agonists. They offer beneficial pharmacological properties and have been widely used in the treatment of cardiovascular diseases. Based on the search result of the domestic and foreign medical databases, the usage of β-blockers including clinical research, animal experiments and clinical work of CPR patients was summarized. Finally, the CPR research progress of β-blockers in recent years was reviewed in the article.

Heat stroke (HS) is a life-threatening illness characterized by core body temperatures above 40 ℃ coupled with central nervous system (CNS) dysfunction, including delirium, convulsions, and/or coma. Its morbidity has increased dramatically in the past few decades. Multiple organ dysfunction syndrome (MODS) is not only the most serious complication of HS, but also the leading cause of deaths. Understanding the pathogenesis, characteristic and advancement pattern of MODS caused by HS will have a profound effect on the clinical treatment, research and mortality decrease. The pathogenesis, injury characteristic of each system and organ, and treatment methods were summarized in this review so as to deepen the clinical recognition of this disease.

Sepsis is a life-threatening organ dysfunction caused by dysregulated host responses to infection. Despite decades of research, it remains the leading cause of death in intensive care units (ICUs). None of the current treatment, including antibiotics, organ protection and liquid resuscitation, is specifically effective for sepsis. Immunosuppression is one of the currently accepted pathogenesis and immunotherapy is one of the hot spot of current sepsis research. Immune related treatments include restricting the release of pathogen toxin and its removal, controlling the excessive inflammatory reaction and apoptosis inhibition, etc. Numerous pre-clinical studies using immunomodulatory agents such as interleukin-7 (IL-7), anti-programmed cell death-1 (PD-1) antibody and others, have demonstrated reversal of T cell dysfunction and improved survival resulting from reviewing recent advances in immunotherapy of sepsis. Therefore, immunotherapy may be a new way of sepsis treatment.

The mechanism of long chain non-coding RNA (lncRNA) is diverse. LncRNA can regulate the expression of genes at multiple levels and is closely related to some pathological process, such as tumor formation, viral replication, inflammatory damage, etc. The abnormal expression of lncRNA is involved in the patho-physiological changes of the disease, and plays a key role in many links, such as the stability of mRNA, the regulation of translation level, protein transport, RNA processing and modification, and so on. The development of sepsis inflammatory injury is a complex process involving multiple genes and pathways, in which the abnormal structure and expression of many encoding genes or non-coding genes exist.This paper review the research progress on lncRNA in the regulation of chondriokinesis, pro-inflammatory cytokines, calcium ion transport, nuclear factor-κB (NF-κB) in signal pathway and other inflammatory lesions, which may provide a new method for the diagnosis and treatment of sepsis.

Objective To explore the application value of control chart in the management of nosocomial infection in intensive care unit (ICU) by using quality control chart to monitor the infectionsin ICU.Methods From October 2011 to June 2016, ventilator-associated pneumonia (VAP), central line-associated bloodstream infection (CLABSI) and catheter-associated urinary tract infection (CAUTI), namely the three catheters, occurred in ICU of the Affiliated Hospital of Guizhou Medical University were monitored and recorded monthly, then the data was imput into the Excel, and the data was analyzed using SPSS. According to the properties of the data, control chart was derived for monitoring nosocomial infections, finding out problems and for taking actions on time.Results From October 2011 to June 2016, the numbers of new patients in ICU were 23-103 cases per month and the median was 45.00 (39.00, 55.50) cases per month. The numbers of new VAP patients were 0-7 cases per month which median was 3.00 (1.00, 4.00) cases per month and the VAP rates were 0-22.58 cases per 1000 ventilation-days which median was 8.62 (3.28, 12.10) cases per 1000 ventilation-days. The numbers of new CLABSI patients were 0-3 cases per month which median was 0.00 (0.00, 1.00) cases per month and the CLABSI rates were 0-14.82 cases per 1000 catheter-days which median was 0.00 (0.00, 5.38) cases per 1000 catheter-days. The numbers of new CAUTI patients were 0-8 cases per month which median was 1.00 (0.00, 2.00) cases per month and the CAUTI rates were 0-14.06 cases per 1000 catheter-days which median was 3.02 (0.00, 5.86) cases per 1000 catheter-days. 57 points of the three catheter-associated infections incidences were continuously monitored monthly, in which some data points overstepped the warning limit, only 1 CAUTI infection incidence overstepped the control limit, the other monthly three catheter-associated infections incidences were in the control range and had no abnormal arrangement occurred, so all of them were in a controlled state. By using the control chart, the situation of nosocomial infections were analyzed scientifically and intuitively, the existing problems were discussed in time, the improvement programs were made, and the three catheter-associated infections were in a controlled state.Conclusion Control chart has the characteristics of simple operation, intuitive results, and finding problems on time, so it can be used in daily monitoring of nosocomial infection and is worthy of generalization.

Objective To investigate the changes of neutrophil extracellular traps (NETs) level in plasma of sepsis patients and judge its clinical value for early diagnosing of sepsis.Methods A prospective observational study was conducted. The patients after surgery aged > 18 years and expected to stay in the ICU > 24 hours admitted to intensive care unit (ICU) of the First Affiliated Hospital of China Medical University from November 2014 to February 2015 were enrolled. According to the criteria of sepsis diagnosis in 1991, patients were divided into non-sepsis group and sepsis group. The healthy people who taken a physical examination were enrolled in the healthy control group. 3 mL peripheral venous blood was collected at 1 hour after admission to ICU. A fasting blood was collected in the healthy control group in the morning. The plasma free DNA (cf-DNA/NETs) was determined by using the fluorescence microplate reader, white blood cell (WBC), neutrophil ratio (NEU), procalcitonin (PCT), C-reactiveprotein (CRP) in peripheral blood of the patients were detected, and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) scores were calculated. The correlation between plasma NETs and the risk factors in sepsis patients was analyzed by Spearman correlation analysis. The value of cf-DNA/NETs and WBC level in the diagnosis of sepsis was analyzed by using the receiver operating characteristic curve (ROC).Results Twenty-three sepsis patients, 20 non-sepsis patients, and 22 healthy persons were enrolled. There were no differences in baseline variables including gender and age among three groups, which indicated baseline data equalization. The plasma concentration of cf-DNA/NETs in sepsis group was significantly higher than that in non-sepsis group and healthy control group (μg/L: 453.44±185.37 vs. 188.35±29.66, 203.83±43.25, bothP < 0.05),and there was no significant difference between last two groups (P > 0.05). WBC, NEU, PCT, CRP, APACHE Ⅱ and SOFA score in sepsis group were significantly higher than those of non-sepsis group [WBC (×109/L): 9.52±5.51 vs. 5.97±2.28, NEU: 0.787±0.110 vs. 0.655±0.067, PCT (mg/L): 7.14 (3.60, 13.29) vs. 6.07 (3.57, 7.91), CRP (mg/L): 64.44±13.14 vs. 27.00±19.47, APACHE Ⅱ: 10.25±4.92 vs. 6.00±1.22, SOFA: 6.0±5.1 vs. 5.0±1.2, allP < 0.05]. Correlation analysis showed that the level of NETs had no obvious correlation with gender, age, WBC, NEU, PCT, CRP, APACHE Ⅱ and SOFA scores (r value was 0.322, 0.262, 0.194, 0.312, 0.227, 0.454, 0.433, 0.333, respectively, allP > 0.05). The area under the ROC curve (AUC) of plasma cf-DNA/NETs for the diagnosis of sepsis was 0.981. When the cut-off valueof plasma cf-DNA/NETs was > 257.96μg/L, the sensitivity was 91.3%, specialty was 95.2%, and Youden index was 0.865. AUC of WBC in the diagnosis of sepsis was 0.663. When the cut-off value of WBC was > 6.0×109/L, the sensitivity was 78.3% and specificity was 25.0%.Conclusion The plasma cf-DNA/NETs levels increased significantly in sepsis patients. In the diagnosis of sepsis, plasma NETs levels had better advantages over WBC. NETs can be used as a biomarker for early diagnosis of sepsis.

Objective To explore the method and performance of using multiple indices to diagnose sepsis and to predict the prognosis of severe ill patients.Methods Critically ill patients at first admission to intensive care unit (ICU) of Changzheng Hospital, Second Military Medical University, from January 2014 to September 2015 were enrolled if the following conditions were satisfied: ① patients were 18-75 years old;② the length of ICU stay was more than 24 hours; ③ All records of the patients were available. Data of the patients was collected by searching the electronic medical record system. Logistic regression model was formulated to create the new combined predictive indicator and the receiver operating characteristic (ROC) curve for the new predictive indicator was built. The area under the ROC curve (AUC) for both the new indicator and original ones were compared. The optimal cut-off point was obtained where the Youden index reached the maximum value. Diagnostic parameters such as sensitivity, specificity and predictive accuracy were also calculated for comparison. Finally, individual values were substituted into the equation to test the performance in predicting clinical outcomes.Results A total of 362 patients (218 males and 144 females) were enrolled in our study and 66 patients died. The average age was (48.3±19.3) years old. ① For the predictive model only containing categorical covariants [including procalcitonin (PCT), lipopolysaccharide (LPS), infection, white blood cells count (WBC) and fever], increased PCT, increased WBC and fever were demonstrated to be independent risk factors for sepsis in the logistic equation. The AUC for the new combined predictive indicator was higher than that of any other indictor, including PCT, LPS, infection, WBC and fever (0.930 vs. 0.661, 0.503, 0.570, 0.837, 0.800). The optimal cut-off value for the new combined predictive indicator was 0.518. Using the new indicator to diagnose sepsis, the sensitivity, specificity and diagnostic accuracy rate were 78.00%, 93.36% and 87.47%, respectively. One patient was randomly selected, and the clinical data was substituted into the probability equation for prediction. The calculated value was 0.015, which was less than the cut-off value (0.518), indicating that the prognosis was non-sepsis at an accuracy of 87.47%. ② For the predictive model only containing continuous covariants, the logistic model which combined acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score and sequential organ failure assessment (SOFA) score to predict in-hospital death events, both APACHE Ⅱ score and SOFA score were independent risk factors for death. The AUC for the new predictive indicator was higher than that of APACHE Ⅱ score and SOFA score (0.834 vs. 0.812, 0.813). The optimal cut-off value for the new combined predictive indicator in predicting in-hospital death events was 0.236, and the corresponding sensitivity, specificity and diagnostic accuracy for the combined predictive indicator were 73.12%, 76.51% and 75.70%, respectively. One patient was randomly selected, and the APACHE Ⅱscore and SOFA score was substituted into the probability equation for prediction. The calculated value was 0.570, which was higher than the cut-off value (0.236), indicating that the death prognosis at an accuracy of 75.70%.Conclusion The combined predictive indicator, which is formulated by logistic regression models, is superior toany single indicator in predicting sepsis or in-hospital death events.

Objective To investigate the suppressive effect of carbon monoxide-releasing molecule Ⅱ (CORM-2) on LPS induced platelet α-granule exocytosis in sepsis via soluble N-ethylmaleimide-sensitive factor attached protein receptor/mammalian uncoordinated 18b (SNARE/Munc18b) complex formation.Methods Blood was collected from healthy volunteers' cubital vein, then platelets were isolated by differential centrifugation. Platelets were randomly divided into 5 groups. The control group did not undergo any treatment, the LPS group received 10 mg/L LPS simulation, the CORM-2 group and iCORM-2 group underwent LPS simulation and immediate administration of CORM-2 (10μmol/L and 50μmol/L) or iCORM-2 (50μmol/L), respectively. Samples were incubated in a CO2-incubator at 37 ℃, 95% humidity, and 5% CO2. Platelet α-granule contents were detected by using standard enzyme linked immunosorbent assay (ELISA), including platelet factor 4 (PF4), platelet derived growth factor-BB (PDGF-BB), and matrix metalloproteinase-2 (MMP-2). The expression of P-selectin was detected by flow cytometer. Transmission electron microscope and immunofluorescence microscope was used to assess platelet α-granules distribution. Expressions of Munc18b and SNARE proteins including vesicle-associated membrane protein-8 (VAMP-8), synaptosomal-associated protein-23 (SNAP-23) and syntaxin-11 (STX-11) were detected by Western Bolt. The SNARE/Munc18b complex formation was detected by immunoprecipitation.Results Compared with the control group, levels of PF4, PDGF-BB, MMP-2 and P-selectinin LPS-induced platelets were found to markedly elevated, while CORM-2 (10μmol/L and 50μmol/L) could decrease platelet α-granule contents exocytosis: [PF4 (μg/L): 7.69±0.58, 6.03±0.71 vs. 10.13±0.82; PDGF-BB (μg/L): 112.71±1.79, 102.91±5.86 vs. 128.78±1.39; MMP-2 (ng/L): 32.94±2.73, 27.58±3.36 vs. 53.26±1.21; P-selectin: (17.14±0.57)%, (15.35±0.68)% vs. (23.78±0.62)%; allP < 0.01]. Transmission electron microscope and immunofluorescence microscope showed that the extent of platelet α-granules assembled to platelet plasma membrane was significantly decreased following CORM-2 treatment. Compared with the control group, the expressions of Munc18b and SNARE proteins and SNARE/Munc18b complex formation in LPS-stimulated platelets were significantly increased, while CORM-2 (10μmol/L and 50μmol/L) inhibited these elevations (Munc18b/GAPDH: 0.80±0.08, 0.69±0.01 vs. 0.99±0.09; VAMP-8/GAPDH: 0.72±0.09, 0.50±0.12 vs. 1.18±0.14; SNAP-23/GAPDH: 1.18±0.22, 0.63±0.10 vs. 1.90±0.08; STX-11/GAPDH: 0.76±0.02, 0.57±0.08 vs. 1.16±0.23; VAMP-8/ Munc18b: 0.65±0.09, 0.53±0.07 vs. 1.21±0.20; SNAP-23/Munc18b: 0.85±0.07, 0.55±0.09 vs. 1.26±0.08; STX-11/ Munc18b: 0.78±0.05, 0.61±0.10 vs. 1.39±0.16; allP < 0.01). Above all, the data showed a dose dependent change.Conclusion We could suggest that CORM-2 suppressed α-granule exocytosis in LPS-stimulated platelets and the potential mechanisms might involve SNARE/Munc18b complex formation.

Objective To explore the effect of toll-like receptor 4 (TLR4), myeloid differentiation protein-2 (MD2), and stromal interaction molecular 1 (STIM1) for regulating human vascular endothelial calcium overload injury and inflammatory reaction induced by bacterial endotoxin (LPS).Methods Human umbilical vein endothelial cells (HUVECs) were cultured in Dulbecco's modification of Eagle's medium (DMEM). ① The levels of TLR4, MD2 and nuclear factor-κB (NF-κB) were detected by reverse transcriotion-polymerase chain reaction (RT-PCR) before and 0.5, 1, 6, 12, 24 hours after LPS stimulation. ② Intracellular calcium peak level was detected by confocal following probe fluo-3 AM loading in HUVEC cells induced with LPS and transfected by psiSTIM or psiTLR. ③ MD2, STIM1 or NF-κB protein level was detected by immunoprecipitation (IP) and immuno-blotting in HUVEC cells which were transfected by TLR4 inhibited expression (psiTLR) for 12 hours and followed by LPS stimulation for 6 hours. ④ HUVEC cells were randomly divided into 6 groups: control group, LPS group, PDTC 0.1 mg/L group, PDTC 1 mg/L group, psiTLR 1 h group and psiTLR 12 h group. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were detected by enzyme linked immunosorbent assay (ELISA) in supernatant. The mRNA levels of STIM1 and NF-κB were detected by RT-PCR.Results ① The mRNA levels of TLR4, MD2, and NF-κB gradually increased after LPS induction and peaked at 6 hours (2-ΔΔCt: 23.52±2.88, 17.43±3.43, 18.13±2.99, respectively), which were statistically significant before the stimulation with LPS (2-ΔΔCt: 7.02±2.81, 5.19±3.22, 8.11±1.42, allP < 0.05). ② Extracellular calcium influx in LPS group was increased significantly higher than control group (nmol/L: 108.13±22.33 vs. 41.57±13.19, P < 0.01). Extracellular calcium influx in psiSTIM+LPS group (nmol/L: 62.61±14.12 vs. 108.13±22.33,P < 0.05) and psiTLR+LPS group (nmol/L: 50.78±8.05 vs. 109.43±20.21,P < 0.01) were both suppressed as compared with LPS group. While extracellular calcium peak level in psiTLR+psiSTIM+LPS group further decreased (nmol/L: 39.31±6.42 vs. 109.43±20.21,P < 0.01). ③ MD2 protein but not STIM1 or NF-κB can be detected in anti-TLR4 precipitates in control (ctrl-) by immunoprecipitation. MD2 protein level increased in anti-TLR4 precipitates in LPS group (ctrl+) and was suppressed in TLR4 inhibiting group (psiTLR). ④ The levels of TNF-α in PDTC 1mg/L group were significantly lower than those of LPS group (ng/L: 0.60±0.24 vs. 1.77±0.66,P < 0.01). The levels of IL-6 in PDTC 0.1 mg/L, 1 mg/L group and psiTLR 12 h group decreased significantly lower than that of LPS group (ng/L: 232.10±63.54, 134.32±37.23, 284.23±56.14 vs. 510.22±89.23, allP < 0.05). Compared to LPS group, the mRNA levels of NF-κB and STIM1 were obviously inhibited in PDTC1 mg/L group and psiTLR 12 h group [NF-κB mRNA (2-ΔΔCt): 17.22±2.35, 13.24±3.54 vs. 30.16±2.06; STIM1 mRNA (2-ΔΔCt): 12.57±2.43, 12.21±2.46 vs. 25.12±2.02, allP < 0.05]. Conclusions TLR4, MD2, NF-κB signal and SOC calcium channel STIM1 mediate LPS induced-calcium influx and inflammatory mediators level in HUVEC cells. Extracellular calcium overload and inflammatory response by endotoxin induction can be effectively inhibited by down-regulation of TLR4, NF-κB and/or STIM1.

Objective To study the predicting value of four different scoring systems such as the acute physiology and chronichealth evaluation Ⅱ (APACHE Ⅱ) score, sequential organ failure assessment (SOFA) score, quick SOFA (qSOFA) score and systemic inflammatory response syndrome (SIRS) score for the prognosis of septic patients. Methods A retrospective analysis were conducted. Septic patients in intensive care unit (ICU) of the First People's Hospital of Chenzhou form July 1st, 2012 to June 30th, 2016 were enrolled.Patients were divided into survival group and death group according to 28-day outcome. The difference of clinic data, the worst clinical index value within 24 hours, whether mechanical ventilation performed on first day, length of stay in ICU, APACHE Ⅱ score, SOFA score, qSOFA score and SIRS score were compared between the two groups. The significant different factors of sepsis outcome in univariate analysis were analyzed by multiple logistic regression, and the ability of four scoring systems was tested by receiver operating characteristic (ROC) curve.Results 311 patients were enrolled in this study (221 survivals, 90 deaths, 28-day mortality rate 28.9%). Univariate analysis showed age, mechanical ventilation ratio, urine output, length of stay in ICU and the fastest heart beat rate (HR), the lowest systolic blood pressure (SBP), the lowest mean arterial pressure (MAP), HCO3-, minimum arterial blood oxygen partial pressure (PaO2), minimum oxygenation index (PaO2/FiO2), the maximum fraction of inspired oxygen (FiO2), Na+, the highest concentration of blood urea nitrogen (BUN), the highest concentration of serum creatinine (SCr), minimum concentration of plasma albumin (Alb), Glasgow coma score (GCS) score, APACHE Ⅱ score, SOFA score, qSOFA score, within 24 hours after diagnosis were significantly different between two groups (allP < 0.05). Multiple logistic regression showed age [odds ratio (OR) = 1.388, 95% confidence interval (95%CI) = 1.074-1.794,P = 0.012], PaO2/FiO2 (OR = 0.459, 95%CI = 0.259-0.812,P = 0.007), concentration of plasma Alb (OR = 0.523, 95%CI = 0.303-0.903,P = 0.020), GCS score (OR = 0.541, 95%CI = 0.303-0.967,P = 0.038) and SOFA scores (OR = 3.189, 95%CI = 1.813-5.610,P = 0.000) were independent risk factors for sepsis outcome. ROC curve test showed the APACHE Ⅱ score, SOFA score and qSOFA score had the ability to predict the outcome in critical ill patients with sepsis, the SOFA score of the most powerful, the area under the ROC curve (AUC) was 0.700,when the cut-off value was 7.5 points, the sensitivity was 73.3% and specificity was 58.8%.Conclusions APACHE Ⅱ score, SOFA score and qSOFA score have the predictive properties for septic patients. SOFA score is an independent prognostic risk factor of sepsis, while qSOFA score can be widely used in clinical practice as the advantage of quick evaluating.