Objective To investigate the renal protective effect of antivenom therapy assisted with hyperbaric oxygen(HBO) in agkistrodon acutus poisoning rat.Methods Ninety-six healthy adult male SpragueDawley rats were randomized into the control group(group A),snake venom poisoning group(group B),antivenom treatment group(group C) and antivenom+ HBO treatment group(group D),24 cases in each group.The group B,C and D were injected with agkistrodon acutus toxin 0.8 × LD50 (LD50 =1.594 mg/kg) by tail vein for establishing the poisoning model.The renal tissue pathological changes after agkistrodon acutus poisoning were observed.In the antivenom treatment group,antivenom(0.8 ×＜ 78 U/kg) was injected by tail vein after successfully constructing model,the group D was given once HBO treatment at 0,4,11 23 h after antivenom injection,while the group A was not given any treatment.Results The rats appeared obvious poisoning symptoms after snake venom intravenous injection.Compared with the group B,therat renal function and coagulation functions in the group C and D were significant improved,more over the group D was better than the group C(P＜0.05).The rats of the group B appeared glomerular hemorrhage,renal capsule expansion,different degrees of congestion in peripheral blood capillaries,renal tubular cavity dilation,cellular fatness,falling of brush border,vacuolation of renal tubular epithelial cells and inflammary cells infiltration in renal interstitial tissue.Along with time lapse,the renal hemorrhage was decreased and inflammatory cells infiltration was increased.The abovelesions in the group C and D were significantly improved.Conclusion The Agkistrodon acutus poisoning can lead to renal damage in rats;the antivenom treatment assisted with HBO has the protective effect on renal injury in agkistrodon acutus poisoning rat,moreover early adopting has better protective effect.

Acute respiratory distress syndrome (ARDS) is considered to be a pulmonary manifestation of systemic inflammatory response syndrome (SIRS), often occurring as a complication of disease, and worsening the prognosis of patients. In recent years, the incidence of trauma has increased year by year. Severe trauma can lead to SIRS, which is one of the common risk factors of ARDS. The spleen is the largest peripheral immune organ of the body, containing a large number of immune cells and secreting inflammatory factors. The inflammatory factors play an important role in the formation of traumatic ARDS. In recent years, the benefits of treating ARDS by inhibiting spleen-induced inflammatory response have gradually been discovered, providing new ideas for the treatment of ARDS. Therefore, the research status of spleen-mediated inflammatory response in traumatic ARDS is of great significance for the prevention and treatment of traumatic ARDS. This article reports the spleen-mediated systemic inflammatory response, the role of inflammatory mediators in the development of ARDS, and the current state of research on ARDS treatment to explore new approaches to the prevention and treatment of traumatic ARDS.

Traumatic brain injury (TBI) is one of the diseases with high morbidity,mortality,and disability,which seriously endangers human health.Primary and secondary injuries caused by TBI are cascade reaction of various pathophysiological interactions.Because of its many injury factors and complex mechanisms,the treatment and therapeutic effect of TBI are limited at present.In recent years,animal experiments and clinical studies have shown that stem cell therapy could alleviate TBI-mediated neurological damage to a certain extent.Therefore,activation of endogenous neural cells response and transplantation of exogenous stem cells may be new strategies for TBI treatment.This article reviews the research progress of activation of endogenous neural cells response and transplantation of exogenous stem cells after TBI,and focuses on the therapeutic effects and possible mechanisms of stem cell transplantation in TBI treatment.

Objective:To study the effect of programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) regulating dendritic cells (DC) on the immune status of sepsis, and analyze the effect of PD-1/PD-L1 on prognosis.Methods:Twenty-five patients with sepsis in the intensive care unit (ICU) of the Affiliated Hospital of Zunyi Medical University from October 2018 to September 2019 were collected and followed up for 28 days. According to the 28-day survival of patients, patients were divided into survival group and death group. Among them, 10 cases were in the survival group and 15 cases were in the death group. Simultaneously, 20 healthy subjects in our hospital during the same period served as the healthy control group. Peripheral blood of patients with sepsis was taken within 24 hours after diagnosis, and the healthy control group was taken at the time of enrollment. Flow cytometry was used to detect the proportion of CD4 +T and CD8 +T cells, the ratio of T cell subsets (CD4/CD8), the expression of PD-1 on CD4 +T and CD8 +T cells, and the expression of PD-L1 and CD86 in DC. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of interleukin-10 (IL-10) and tumor necrosis factor-α(TNF-α) in serum. Spearman correlation analysis was used to analyze the correlation between CD11c +PD-L1 and CD4 +PD-1, CD8 +PD-1, TNF-α, DC, CD11c +CD86, T cell subpopulation ratio, CD4 +T cells, CD8 +T cells, and IL-10. Binary Logistic regression was used to analyze the risk factors affecting the death of patients with sepsis, and receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of independent risk factors on the prognosis of patients. Results:The scores of acute physiology and chronic health evaluationⅡ (APACHEⅡ) and sequential organ failure assessment (SOFA) in the death group were higher than that in the survival group (APACHEⅡ score: 27.0±7.3 vs. 17.0±3.9, SOFA score: 15.1±4.1 vs. 10.7±2.7, both P < 0.05). The ratio of T cell subsets in the survival group and the death group was less than 1, the death group was lower than that in the survival group (CD4/CD8: 0.54±0.15 vs. 0.79±0.09, P < 0.05), and the ratio of T cell subsets in the healthy control group was greater than 1. Compared with healthy control group, the levels of CD4 +T cells, CD8 +T cells, CD11c +DC, CD11c +CD86, IL-10 and TNF-α in survival group and death group were significantly decreased, the level of CD4 +PD-1, CD8 +PD-1, CD11c +PD-L1 were significantly increased, and the changes in the above indicators in the death group were significant compared with the survival group [CD4 +T cells: 0.14±0.07 vs. 0.22±0.08, CD8 +T cells: 0.24±0.07 vs. 0.28±0.10, CD11c +DC: 0.84±0.14 vs. 0.93±0.03, CD11c +CD86: (58.83±20.77)% vs. (78.24±9.39)%, IL-10 (ng/L): 34.22±13.98 vs. 18.49±5.55, TNF-α(ng/L): 95.30±29.33 vs. 67.00±20.16, CD4 +PD-1: (39.58±10.08)% vs. (27.03±6.35)%, CD8 +PD-1: (38.77±11.91)% vs. (29.15±8.37)%, CD11c +PD-L1: (21.13±11.54)% vs. (12.11± 8.34)%, all P < 0.05]. Spearman correlation analysis showed that CD11c +PD-L1 was positively correlated with CD4 +PD-1, CD8 +PD-1, and IL-10 ( r values were 0.748, 0.713, 0.898, all P < 0.05), while was negatively correlated with DC, CD11c +CD86, T cell subpopulation ratio, CD4 +T cells, CD8 +T cells, and TNF-α( r values were -0.587, -0.906, -0.840, -0.706, -0.513, -0.820, all P < 0.05). Multivariate binary Logistic regression analysis showed that CD4 +T PD-1 was an independent risk factor for the prognosis of sepsis patients [odds ratio ( OR) = 1.463, 95% confidence interval (95% CI) = 1.032-2.074, P = 0.033]. ROC curve analysis showed that CD4 +TPD-1 had certain predictive value for the prognosis of patients with sepsis [area under ROC curve (AUC) = 0.857, 95% CI was 0.709-1.000, P < 0.01). When the best predictive value was 34.48%, the sensitivity, specificity, and accuracy were 66.7%, 90.0%, and 85.7% respectively. Conclusions:Up-regulation of PD-1/PD-L1 in peripheral blood could inhibit the activation and proliferation of DC, affect the activation of T cells, and induce immunosuppressive state. PD-1/PD-L1 can reflect the immune status of patients with sepsis. The expression of PD-1 on CD4 +T cells may have important significance for the evaluation of prognosis.

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) is widely used for targeted genomic and epigenomic modifications and imaging in cells and organisms, and holds tremendous promise in clinical applications. The efficiency and accuracy of the technology are partly determined by the target binding affinity and residence time of Cas9-single-guide RNA (sgRNA) at a given site. However, little attention has been paid to the effect of target binding affinity and residence duration on the repair of Cas9-induced DNA double-strand breaks (DSBs). We propose that the choice of DSB repair pathway may be altered by variation in the binding affinity and residence duration of Cas9-sgRNA at the cleaved target, contributing to significantly heterogeneous mutations in CRISPR/Cas9 genome editing. Here, we discuss the effect of Cas9-sgRNA target binding and residence on the choice of DSB repair pathway in CRISPR/Cas9 genome editing, and the opportunity this presents to optimize Cas9-based technology.