Sepsis is currently the leading cause of death in the intensive care unit, and its survivors also experience long-term immunosuppression and high rates of recurrent infections. At present, the clinical treatment of sepsis is still based on antibiotics, intravenous rehydration, and vasopressors, and there is no targeted drug treatment. However, as the rate of antibiotic resistance continues to increase, immunotherapy is highly anticipated as a new treatment. Patients with sepsis are often accompanied by acute leukocyte immune dysfunction and immunosuppression, which may be an important risk factor for the increasing morbidity and mortality of patients. Targeted inhibition of specific cell surface inhibitory immune checkpoint receptors and ligands, such as programmed death receptor-1 (PD-1), programmed death-ligand 1 (PD-L1), and other targets, can improve the host’s resistance to infection. In this paper, the research progress of PD-1 and PD-L1 in the immune response to sepsis was summarized to provide a theoretical basis for their further application in the treatment of sepsis in the future.

Sepsis is a common disease in intensive care units (ICU), and the resulted multi-organ dysfunction syndrome (MODS) is the main cause of death in patients with severe sepsis. The cardiovascular system is one of the most important target organ for sepsis. The severity of cardiac dysfunction is closely related to the clinical prognosis of patients with sepsis. Studies have reported that various cytokines are expressed during sepsis. They have influence on myocardial contractile function, mitochondrial function and self-regulation. Where after, it will induce cardiomyocyte apoptosis, which can lead to myocardial dysfunction. In this article, the pathogenesis of sepsis-induced myocardial dysfunction (SIMD) were reviewed to further clarify the pathogenesis of SIMD, and provide theoretical basis for subsequent research.

Objective: To investigate the effect of estrogen on expression of the cysteine-rich secretory protein containing LCCL domain 2 (CRISPLD2) in myocardium of lipopolysaccharide (LPS)-induced mice model of sepsis. Methods: Totally 12 female and 12 male Balb/c mice of specific pathogen-free (SPF) level with 7 weeks were served as objectives. The female and male mice were randomly divided into model groups and control groups, respectively, with 6 mice in each group. The model of sepsis was reproduced by intraperitoneal injection of 10% LPS (5 mg/kg), and the mice in control groups were injected with the same volume of normal saline. The general condition of mice during experiment was observed at 24 hours after injection. All the mice were sacrificed and the heart was harvested after collecting the whole blood. The concentration of estrogen in serum was determined by double antibody sandwich enzyme linked immunosorbent assay (ELISA). The myocardial tissue homogenate was prepared at the same time, and the total protein was extracted. The expression level of CRISPLD2 was determined by Western Blot. Pearson correlation analysis was used to analyze the bivariate correlation. Results: All of the experimental mice survived at 24 hours after injection. The mice in the model groups showed disorder and gray signs of body hair, with diarrhea and decreased appetite. No significant abnormality was observed in the control groups. There was no significant difference in the body weight or concentration of estrogen in serum between model and control group of both female and male mice [body weight (g): 24.6±1.8 vs. 24.5±1.3 in male mice, 18.0±0.8 vs. 17.5±1.1 in female mice; estrogen (ng/L): 11.93±2.59 vs. 12.17±3.87 in male mice, 28.20±5.75 vs. 29.82±6.10 in female mice, all P > 0.05]. There was no statistical difference in the expression of CRISPLD2 in myocardium between male control mice and female control mice (gray value: 1.02±0.19 vs. 1.00±0.11, P > 0.05). No significant difference in the expression of CRISPLD2 in myocardium was found between female sepsis mice and female control mice (gray value: 1.05±0.13 vs. 1.00±0.11, P > 0.05). The expression of CRISPLD2 in myocardium of male sepsis mice was significantly lower than that of male control mice (gray value: 0.29±0.08 vs. 1.02±0.19, P < 0.01), and it was significantly lower than that of female sepsis mice (P < 0.01). It was shown by correlation analysis that the expression level of CRISPLD2 in myocardium of sepsis mice was significantly correlated with serum estrogen concentration [R² = 0.736, 95% confidence interval (95%CI) = 0.560-0.960, P < 0.001]. Conclusions In female mice with sepsis, the expression of CRISPLD2 is comparable to that of female healthy mice. It is suggested that estrogen can maintain the expression of CRISPLD2 in LPS-induced septic mice at the normal level.

OBJECTIVE: To investigate the effect of estrogen on expression of the cysteine-rich secretory protein containing LCCL domain 2 (CRISPLD2) in myocardium of lipopolysaccharide (LPS)-induced mice model of sepsis. METHODS: Totally 12 female and 12 male Balb/c mice of specific pathogen-free (SPF) level with 7 weeks were served as objectives. The female and male mice were randomly divided into model groups and control groups, respectively, with 6 mice in each group. The model of sepsis was reproduced by intraperitoneal injection of 10% LPS (5 mg/kg), and the mice in control groups were injected with the same volume of normal saline. The general condition of mice during experiment was observed at 24 hours after injection. All the mice were sacrificed and the heart was harvested after collecting the whole blood. The concentration of estrogen in serum was determined by double antibody sandwich enzyme linked immunosorbent assay (ELISA). The myocardial tissue homogenate was prepared at the same time, and the total protein was extracted. The expression level of CRISPLD2 was determined by Western Blot. Pearson correlation analysis was used to analyze the bivariate correlation. RESULTS: All of the experimental mice survived at 24 hours after injection. The mice in the model groups showed disorder and gray signs of body hair, with diarrhea and decreased appetite. No significant abnormality was observed in the control groups. There was no significant difference in the body weight or concentration of estrogen in serum between model and control group of both female and male mice [body weight (g): 24.6±1.8 vs. 24.5±1.3 in male mice, 18.0±0.8 vs. 17.5±1.1 in female mice; estrogen (ng/L): 11.93±2.59 vs. 12.17±3.87 in male mice, 28.20±5.75 vs. 29.82±6.10 in female mice, all P > 0.05]. There was no statistical difference in the expression of CRISPLD2 in myocardium between male control mice and female control mice (gray value: 1.02±0.19 vs. 1.00±0.11, P > 0.05). No significant difference in the expression of CRISPLD2 in myocardium was found between female sepsis mice and female control mice (gray value: 1.05±0.13 vs. 1.00±0.11, P > 0.05). The expression of CRISPLD2 in myocardium of male sepsis mice was significantly lower than that of male control mice (gray value: 0.29±0.08 vs. 1.02±0.19, P < 0.01), and it was significantly lower than that of female sepsis mice (P < 0.01). It was shown by correlation analysis that the expression level of CRISPLD2 in myocardium of sepsis mice was significantly correlated with serum estrogen concentration [R² = 0.736, 95% confidence interval (95%CI) = 0.560-0.960, P < 0.001]. CONCLUSIONS In female mice with sepsis, the expression of CRISPLD2 is comparable to that of female healthy mice. It is suggested that estrogen can maintain the expression of CRISPLD2 in LPS-induced septic mice at the normal level.
Animals ; Cysteine ; Estrogens ; Female ; Lipopolysaccharides ; Male ; Mice ; Myocardium ; 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 observe the effects of vaporized perfluorocarbon (PFC) combined with exogenous pulmonary surfactant (PS) inhalation on rabbit models of acute lung injury (ALI).Methods Thirty-two New Zealand rabbits were randomly divided into four groups: ALI group, combination treatment group, PFC group, and PS group (each groupn = 8 rabbits). The rabbit model of ALI was induced by the whole lung normal saline lavage. After modeling, in the combined group, 3 mL/kg vaporized perfluorooctyl bromide/dipalmitoylphosphatidylcholine (PFOB/DPPC) emulsion was inhaled, the rabbits in PFC and PS groups were treated with vaporized PFOB emulsion and vaporized DPPC emulsion 3 mL/kg inhalation respectively, and in the ALI group was given the same amount of vaporized normal saline inhalation. In each group, before modeling for 30 minutes (basic value), after modeling for 1 hour and after treatment at 0 minute, 30 minutes, 2 hours, 4 hours, the respiratory rate (RR), oxygenation index (OI), dynamic lung compliance (Cdyn) were observed, and the lung coefficient (LI) and lung permeability index (LPI) were calculated; the levels of serum tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured by double antibody sandwich enzyme-linked immunosorbent assay (ELISA); the lung tissue was collected and the lung pathological changes were observed under macroscopic and microscopic observation.Results Aftermodeling, the levels of OI, Cdyn were quickly lowered, RR became significantly elevated, and there were obvious edema, hemorrhage and exudation in lung tissue of ALI group. The levels of OI were significantly increased in combined group and PFC group compared with the level in ALI group after treatment at 0 minute initially [mmHg (1 mmHg = 0.133 kPa): 231.0±16.7, 221.4±19.0 vs. 189.5±21.0, both P < 0.05], while the level of OI in PS group was increased significantly until 4 hours after treatment, being higher than that in ALI group (mmHg: 297.0±20.7 vs. 243.3±36.7,P < 0.05); RR was decreased significantly in combined treatment group at 30 minutes after treatment compared with that in ALI group (bpm: 151.1±13.3 vs. 178.5±32.0,P < 0.05), while the RR in PFC group and PS group were not increased significantly until 4 hours after treatment being higher than that in ALI group (bpm: 129.3±14.3, 133.1±13.9 vs. 157.5±32.5, bothP < 0.05). Compared to ALI group, the three treatment groups resulted in significant improvement in Cdyn right at 0 minute (mL/cmH2O: 1.64±0.10, 1.45±0.10, 1.43±0.09 vs. 0.57±0.05, allP < 0.05), their LPI, LI and inflammatory cytokines were significantly decreased [LPI (×10-5): 4.21±0.42, 4.76±0.55, 4.87±0.49 vs. 5.56±0.52, LI: 8.04±0.58, 8.90±0.88, 9.22±0.71 vs. 10.85±0.73, TNF-α (ng/L): 50.05±4.91, 56.18±5.54, 63.60±5.96 vs. 73.60±5.27, IL-1β (ng/L): 34.27±4.55, 40.29±5.03, 48.13±6.38 vs. 54.71±4.26, allP<0.05], and pulmonary edema, congestion and inflammatory cell infiltration were obviously ameliorated (pathological scores: 3.74±0.58, 4.50±0.75, 5.29±0.72 vs. 6.13±0.72, P < 0.05). Cdyn levels were increased significantly in combined treatment group at 0 minute, 30 minutes, 4 hours after treatment compared with thosein PFC and PS group, but there were no significant differences between PFC and PS group. Levels of LI, LPI, inflammatory factors and pathological scores were decreased significantly in combined treatment group compared with those in PFC and PS group, the degrees of improvement of inflammatory factors and pathological scores in PFC group were more obvious than those in PS group (allP < 0.05).Conclusions PFOB combined with DPPC inhalation can provide greater oxygen delivery, reduce the pro-inflammatory cytokines, supplement PS and influence its distribution on the surface of lung, which might lead to a marked and sustained improvement in oxygenation, pulmonary function and amelioration of lung edema and inflammatory reaction in saline lavage induced lung injury of rabbits.

Objective To study the changes of PI3K/Akt/GSK3β signaling pathway during resuscitation with neck cooling in order to explore the relationship between the protective effect of neck cooling and the phosphorylation of PI3K/Akt and GSK3β.Methods Thirty rabbits were randomly(random number) divided into five groups, and models of cadiac arrest were induced by ventricular fibrillation(VF, the positive electrode in the right ventricle and negative pole on the apex of heart) for 4 min.In sham group,a electrode was placed into right ventricle without electric current conducted, and CA was not induced.The rabbits were sacrificed and specimens were taken at 24 hours after modeling.In normothermia treat group(NT group),resuscitation was carried out to restoration of spontaneous circulation(ROSC),and the rabbits were sacrificed and specimens were taken at 24 hours after modeling.In intra-arrest therapeutic hypothermia group (IATH group), rapid neck cooling was initiated at the same time with CPR,and the target brain temperature was set at 34 ℃ maintained for 4 hours after ROSC.Rabbits were sacrificed and specimens were taken at 24 hours after modeling.In recovery period cooling + LY294002 group(PATH+LY294002 group), LY294002 was injected intra-ventricularly at 20 minutes before resuscitation.Rapid neck cooling was started at the same time with CPR,and the target brain temperature was set at 34 ℃ maintained for 4 hours after ROSC.The rabbits were sacrificed and specimens were taken at 24 hours after modeling.In post-arrest therapeutic hypothermia group (PATH group), rapid neck cooling was begun after CPR for 1 hour,and the target brain temperature was set at 34 ℃ maintained for 4 hours after ROSC.The rabbits were sacrificed and specimens were taken at 24 hours after modeling.Animals were sacrificed by using overdose anesthetic drug.Western blot was used to detect the level of Akt p-Akt GSK-3β p-GSK-3β (ser9) protein, and TUNEL was used to observe apoptosis of tissues in each group.Multiple comparisons were performed with one-way analysis of variance (ANOVA).Results Compared with Sham group, Akt (Thr-308) phosphorylation (P-AKT) and P-GSK-3β levels in the brain neuron cytoplasm in 24 hours after CPR resuscitation in NT group was significantly reduced, and showed a gradual reduction trend (P<0.05);the P-AKT and P-GSK-3β levels in the brain neuron cytoplasm in 24 hours after CPR resuscitation in IATH group were significantly enhanced compared with NT group (P<0.05);the levels of these two kinds of protein at one hour after resuscitation in PATH group were significantly enhanced compared with NT group (P<0.05), but lower in IATH group.Intra-ventricularly injection of LY294002 made the effect of hypothermia lost, indicating that LY294002 inhibited the phosphorylation of Akt.Apoptosis cells were significantly reduced in IATH group and normothermia theatment group compared with PATH group and LY294002 group(P<0.05).Conclusions Neck cooling can reduce apoptosis in rabbit brain cells after recovery, and the protective effect on brain is best in intra-arrest therapeutic hypothermia group.LY294002 specifically block the PI3K/Akt pathway, and the protective effect of cooling on the brain can be abolished,indicating hypothermia protects the neurological function via activation of PI3K/Akt pathway.Neck cooling protects the neurological function by activating PI3K/Akt/GSK-3β, promoting the Akt activation, and increasing the expression of P-GSK3β.Specific Akt inhibitor LY294002 inhibits Akt phosphorylation of brain tissue recovery and further inhibit the phosphorylation of GSK-3β, thus abolishing protective effect of cooling on neurological function.

Pulmonary embolism (PE) refers to the endogenous or exogenous emboli blocking pulmonary trunk or branches, causing clinical and pathophysiological syndrome of pulmonary circulation disorder, the incidence rate is high. Sometimes PE patients were lack of specific symptoms and signs, or without any symptoms, which often result in misdiagnosis, un-timely diagnosis, and the delay of treatment. A PE case with syncope, vomiting and shock, which was proved to be pulmonary artery trunk and branch wide embolism later, was presented so as to improve the understanding of the disease.

Objective To investigate the epidemiological characteristics of traumatic cervical spinal cord injury (TCSCI) in ICU.Method The data of patients with TCSCI admitted from October 2010 to March 2016 in the intensive care unit were retrospectively studied.The general epidemiological data included:gender,age,marital status,occupation,cause of injury,injury severity,injured segment (ASIA grade),and complications were collected.Results There were 109 patients identified to have TCSCI with mean age of 53.72 ± 14.86 years (25.69％ patients in the range of 60-69 years old).The male to female ratio was 9:1,and the most were married.The majority of individuals were retired (30.27％),and the main causes of injury were traffic accidents and tumble.The C5 segment of the spine was the most vulnerable to be injured,and then the C4 segment was the nest in turn.There were up to 30.28％ patients suffered from multiple injuries,and 26.61％ patients also had a craniocerebral injury.Bedsore and respiratory system complications were the two leading complications,and 83 patients suffered from at least one system dysfunction with respiratory dysfunction accounted for 98.79％ and circulatory dysfunction accounted for 65.06％.Fifty-one patients presented more than two system dysfunctions (46.79％).Twenty patients (18.35％) died.Conclusion Patients with TCSCI in ICU presented specially characteristic features.Traffic accidents were the main cause of TCSCI,and fall accidents were one of the main causes in the elderly.The mortality of TCSCI was high,especially in males.The complication rate was relatively high and the most common complications were water and electrolyte disturbance and respiratory dysfunction.Multiple organ dysfunction incidences might be associated with the ASIA grades.

The successful establishment of animal models of cardiac arrest-cardiopulmonary resuscitation (CA-CPR) undoubtedly provided an important basis for exploring the method of cardiopulmonary resuscitation (CPR) and advanced cardiovascular life support (ACLS). However, pathophysiology varied with the etiology of cardiac arrest (CA). Therefore, preparation of similar animal models according to etiology was the basis for pathophysiological changes research. Compared with other animals, the rabbits had both the advantages of large and small animals, so they became common research object for the CA-CPR model. This paper reviewed the common methods of animal models of CA-CPR in rabbits. In this review, the methods, criteria, advantages, disadvantages and precautions of each model were analyzed, which would provide useful reference for CPR researchers.