Role of coagulation dysfunction in thrombocytopenia-related death in patients with septic shock / 中华危重病急救医学

OBJECTIVE@#To explore the effect of thrombocytopenia on the prognosis of patients with septic shock and its mechanism in leading to death.@*METHODS@#A retrospective case-control study was conducted. Patients with septic shock admitted to emergency intensive care unit (EICU) and intensive care unit (ICU) in Peking University People's Hospital from April 1, 2015 to January 31, 2023 were enrolled. Patients were divided into the thrombocytopenia group and the non-thrombocytopenia group, according to whether the minimum platelet count was less than 100×109/L within 24 hours after admission to ICU. The outcome index was the mortality during ICU stay. The baseline data, hospitalization information and laboratory test results of the two groups were compared, and the risk factors of in-hospital death were analyzed by Logistic regression, and the mediation effect was performed by Bootstrap method.@*RESULTS@#A total of 301 patients with septic shock were enrolled, of which 172 (57.1%) had thrombocytopenia and 129 (42.9%) did not. There were significant differences between the two groups in age, mortality, disseminated intravascular coagulation (DIC), continuous renal replacement therapy, and level of creatinine, urea nitrogen, total bilirubin, white blood cell count, lymphocyte count, prothrombin time (PT) and activated partial thromboplastin time (APTT). Univariate Logistic regression analysis showed thrombocytopenia [odds ratio (OR) = 4.478], continuous renal replacement therapy (OR = 4.601), DIC (OR = 6.248), serum creatinine (OR = 1.005), urea nitrogen (OR = 1.126), total bilirubin (OR = 1.006) and PT (OR = 1.126) were risk factors of death during hospitalization in patients with septic shock (all P < 0.05). Multivariate Logistic regression analysis showed that thrombocytopenia [OR = 3.338, 95% confidence interval (95%CI) was 1.910-5.834, P = 0.000], continuous renal replacement therapy (OR = 3.175, 95%CI was 1.576-6.395, P = 0.001) and PT (OR = 1.077, 95%CI was 1.011-1.147, P = 0.021) were independent risk factors for in-hospital mortality in patients with septic shock. Mediation analysis showed that 51% of the deaths due to thrombocytopenia in patients with septic shock were due to coagulopathy.@*CONCLUSIONS@#Thrombocytopenia is a powerful predictor of death in septic shock patients, and half of all thrombocytopenia-related deaths may be due to abnormal coagulation function.

Artemisinins inhibit oral candidiasis caused by Candida albicans through the repression on its hyphal development / 国际口腔科学杂志·英文版

Candida albicans is the most abundant fungal species in oral cavity. As a smart opportunistic pathogen, it increases the virulence by switching its forms from yeasts to hyphae and becomes the major pathogenic agent for oral candidiasis. However, the overuse of current clinical antifungals and lack of new types of drugs highlight the challenges in the antifungal treatments because of the drug resistance and side effects. Anti-virulence strategy is proved as a practical way to develop new types of anti-infective drugs. Here, seven artemisinins, including artemisinin, dihydroartemisinin, artemisinic acid, dihydroartemisinic acid, artesunate, artemether and arteether, were employed to target at the hyphal development, the most important virulence factor of C. albicans. Artemisinins failed to affect the growth, but significantly inhibited the hyphal development of C. albicans, including the clinical azole resistant isolates, and reduced their damage to oral epithelial cells, while arteether showed the strongest activities. The transcriptome suggested that arteether could affect the energy metabolism of C. albicans. Seven artemisinins were then proved to significantly inhibit the productions of ATP and cAMP, while reduced the hyphal inhibition on RAS1 overexpression strain indicating that artemisinins regulated the Ras1-cAMP-Efg1 pathway to inhibit the hyphal development. Importantly, arteether significantly inhibited the fungal burden and infections with no systemic toxicity in the murine oropharyngeal candidiasis models in vivo caused by both fluconazole sensitive and resistant strains. Our results for the first time indicated that artemisinins can be potential antifungal compounds against C. albicans infections by targeting at its hyphal development.

Photorhabdus virulence cassette promotes bacterial invasion into macrophages by activating NF-κB and MAPK signaling pathway / 生物工程学报

Photorhabdus is a Gram-negative bacterium from the family Enterobacteriaceae that lives in a symbiotic association with nematode or insects. In addition to the role of being insect pathogens, one species called Photorhabdus asymbiotica (Pa) causes human infection around the world. Nevertheless, how does this transkingdom infection occur remains elusive. Here we focus on one pathogenic determinant called Photorhabdus virulence cassette (PVC) that is founded in the Pa genome and many other pathogens. The RNA-seq and qPCR data showed that the NF-κB and MAPK pathways were drastically activated in the PVC-treated mammalian macrophages. Western blotting assays using samples treated with various inhibitors of the affected pathways confirmed the results we have observed for MAPK pathway previously. p65 translocation assays validated the NF-κB activation in the macrophages after PVC treatment. Moreover, the bacterial phagocytosis by macrophage was also promoted by PVC at the early stage, and this phagocytosis was inhibited by cytoskeleton inhibitors. Thus, the results indicated that PVC is involved in the bacterial invasion by activating NF-κB and MAPK signaling pathway, providing a new perspective for analyzing the pathogenicity of Pa in human infections.

High flow nasal cannula in patients after trachea extubation / 中华危重病急救医学

Acute respiratory failure (ARF) is one primary cause of intensive care unit (ICU) admittance, which is usually treated with intubation and mechanical ventilation in order to maintain a necessary ventilation and oxygenation function. After the remove of trachea tube, available oxygenation supports include nasal cannula, venturi mask, non-invasive ventilator and high flow nasal cannula (HFNC). In this articlewe reviewed the physiological mechanism related to HFNC therapy and trails about the application of HFNC in extubated patients. HFNC can provide well heated and humidified high flow gas with a high concentration of oxygen, which can improve the oxygenation and degree of comfort of patients after extubation. Furthermore, HFNC can improve the prognosis of these patients. However, HFNC has little influence on non-ventilation related factor and severe dysfunction of ventilation, so its indication and risk factor of treatment failure should be further evaluated with randomize controlled trials.

Association between the expression of ve-cadherin and mesentery microcirculation blood flow of sepsis CASP rats and its clinical significance / 国际外科学杂志

Objective To monitor the association between the expression of ve-cadherin and mesentery microcirculation blood flow of sepsis CASP rats,Analysis the relationship of each other.Methods Based on the standard criteria,we established sepsis CASP rats,and the rats were divided into several groups according to the gauge of the vein detained needle in the ascending colon,every group has six rats.The groups consisted of Sepsis A group 22 G(0.9 mm× 25 mm,33 ml/min),sepis B group 20 G(1.1 mm ×32 mm,54 ml/min),sepsis C group 18 G(1.3 mm ×32 mm,80 ml/min),sepsis D group 14 G(2.0 mm ×45 mm,270 ml/min),in addition we established the control group.Real-time observation was performed by microscope on the 6 h's blood velcocity of each sepsis CASP rats group.Then we applied the immunohistochemistry to quantitatively analyze the expression of ve-cadherin of each group.Results The blood velcocity of the mesentery microcirculation in control group was (583.21 ±52.39) μm/s,it was higher compared with the sepsis D group(213.30 ±52.39) μm/s (P ＜0.05),the blood velocity in sepsis A group was (482.71 ± 58.62) μm/s,higher compared with the sepsis D group(P ＜ 0.05).The score of the immunohistochemistry quantitative analysis of mesentery ve-cadherin in control group was 11.17 ±0.34,higher compared with the sepsis D group(5.43 ±0.43)(P ＜0.01).The score of sepsis A group was 10.07 ±0.30,higher compared with the sepsis D group(P＜0.05).Conclusions The expression of ve-cadherin of sepsis CASP rats had positive correlation with the blood velocity of the mesentery microcirculation of sepsis CASP rats,and it can indirectly reflect the degree of the sepsis.