New findings on CD16brightCD62Ldim neutrophil subtypes in sepsis-associated ARDS: an observational clinical study.

Background: The CD16brightCD62Ldim neutrophil subtype is a recently identified neutrophil subtype. The aim of this study was to evaluate changes of peripheral blood CD16brightCD62Ldim neutrophils in patients with sepsis-associated ARDS. Methods: We prospectively recruited adult patients with sepsis-associated ARDS in the intensive care unit (ICU). Patient demographic data, medical history information, and laboratory data were collected within 48 hours of enrollment, and flow cytometry was applied to analyze the CD16brightCD62Ldim neutrophil subtype in the patients' peripheral blood. Multifactor COX regression models were used to analyze factors affecting prognosis, and Spearman correlation coefficients were used to analyze clinical and laboratory indicators affecting complications of infection. Results: Of the 40 patients, 9 patients died by the 28-day follow-up, indicating a mortality rate of 22.5%. Patients in the nonsurvival group had higher CD16brightCD62Ldim neutrophil levels. Patients with sepsis-associated ARDS who had a baseline proportion of CD16brightCD62Ldim neutrophil subtypes to total neutrophils in peripheral blood >3.73% had significantly higher 28-day mortality, while patients with CD16brightCD62Ldim neutrophil subtypes counts >2.62×109/L were also associated with significantly higher 28-day mortality. The percentage of the CD16brightCD62Ldim neutrophil subtype (HR=5.305, 95% CI 1.986-14.165, p=0.001) and IL-8 (HR=3.852, 95% CI 1.561-9.508, p=0.003) were independent risk factors for the development of infectious complications in patients with sepsis-related ARDS. The percentage of CD16brightCD62Ldim neutrophil subtypes predicted an AUC of 0.806 (95% CI 0.147-0.964, P=0.003) for the development of infectious complications, and 0.742 (95% CI 0.589-0.895, P=0.029) for the prediction of death within 28 days. Conclusion: We identified for the first time that CD16brightCD62Ldim neutrophils are elevated in patients with sepsis-associated ARDS and are associated with infectious complications and poor prognosis. The percentage of CD16brightCD62Ldim neutrophil subtypes may serve as a predictor of the development of infectious complications in patients with ARDS.

LncRNA LUADT1 is Upregulated in Mantle Cell Lymphoma and Modulates TRIM11 by Sponging miR-24-3p to Inhibit Cell Apoptosis.

The microRNA MiR-24-3p suppresses cancer progression by targeting TRIM11. The long noncoding RNA LUADT1 has been reported to promote lung adenocarcinoma proliferation. We found LUADT1 may form base pairing with miR-24-3p. This study aimed to explore the interactions among LUADT1, miR-24-3p, and TRIM11 in mantle cell lymphoma (MCL). Our study recruited 40 MCL patients and 40 healthy volunteers. Tumor tissues were collected from 40 newly diagnosed MCL patients and embedded in paraffin wax. B lymphocytes were isolated from all tissue samples by using CD19+ magnetic beads and DETACHaBEAD CD19. Human MCL cell line Grante-519 and JeKo-1 were transfected with LUADT1 and TRIM11 expression vectors, microRNA mimics or inhibitors. Then, quantitative polymerase chain reaction and Western blot were used to detect the level of relative messenger RNA and protein expression, respectively. Flow cytometry was performed to detect the apoptosis rate. LUADT1 and miR-24-3p were upregulated while TRIM11 was downregulated in MCL both in tissues and cell lines compared with hyperplastic lymphadenitis and peripheral lymphocyte cells. Bioinformatics analysis showed that LUADT1 may bind miR-24-3p, which can target TRIM11. Correlation analysis showed that LUADT1 was not significantly correlated with miR-24-3p. However, it was positively and significantly correlated with TRIM11. In MCL cells, LUADT1 overexpression led to upregulated TRIM11, whereas miR-24-3p overexpression led to downregulated TRIM11. Cell apoptosis analysis showed that LU-ADT1, miR-24-3p inhibitor and TRIM11 overexpression led to decreased apoptotic rate of MCL cells, whereas miR-24-3p overexpression led to an increased apoptotic rate of MCL cells. In addition, miR-24-3p overexpression attenuated the effects of LUADT1 overexpression. Therefore, LUADT1 was upregulated in MCL and could modulate TRIM11 by sponging miR-24-3p to inhibit cancer cell apoptosis.

Are you using the third definition to diagnose sepsis in clinic?-A survey among Chinese intensivists.

BACKGROUND: Since sepsis-3 definition is more accurate and sensitive than previous sepsis definition, implementation the newest diagnosis criteria could definitely bring more benefit to sepsis patients. This study was done to identify the level of current intensivists' knowledge regarding the third international consensus definitions for sepsis and septic shock and its implementation for the diagnosis of sepsis among Chinese adult intensive care units (ICUs). METHODS: A nationwide survey amongst critical care physicians was designed. The questionnaires measured the understanding and the frequency of diagnosis of sepsis and septic shock according to the third international consensus definitions for sepsis and septic shock. One thousand random physician members of Chinese Society of Critical Care Medicine were involved in the survey. A 5-point Likert scale (totally understand, partially understand, understand, hardly understand, do not understand) was used to elicit answers about the degree of understanding the sepsis-3 definition. The other 5-point Likert scale (always, often, sometimes, rarely, never) was used to elicit answers about the frequency of diagnosing sepsis according to the sepsis-3 definition. RESULTS: There were 59 (16.1%) intensivists who could completely understand the sepsis-3 definition. Less practiced intensivists could understand the sepsis-3 definition better than more practiced intensivists (P<0.001). Intensivists from university teaching hospitals understand the sepsis-3 definition better than the intensivists from the community hospitals (P<0.001). Intensivists from small-sized ICUs understand the sepsis-3 definition better than intensivists from big-sized ICUs (P<0.001). There were 60 (16.4%) intensivists who always diagnose sepsis according to the sepsis-3 definition since sepsis-3 published. Less practiced intensivists prefer using the sepsis-3 definition to diagnose sepsis compared with more practiced intensivists (P<0.001). Intensivists from university teaching hospitals prefer using the sepsis-3 definition to diagnose sepsis compared with the intensivists from the community hospitals (P<0.001). Intensivists from small-sized ICUs prefer adapting sepsis-3 definition to diagnosis sepsis compared with intensivists from big-sized ICUs (P<0.001). CONCLUSIONS: In current China, the sepsis-3 definition is well understood and accepted by intensivists.

Effect of TrkB-PLC/IP3 pathway on intestinal inflammatory factors and enterocyte apoptosis in mice with colitis.

In this study, we aimed to explore the effect of TrkB-PLC/IP3 pathway on intestinal inflammatory factors and enterocyte apoptosis in mice with colitis. The mouse model of ulcerative colitis was established by medication, and 40 SPF C57BL/6J mice (8 weeks old) were randomly divided into normal group (healthy mice, n = 10), control group (sham-operated mice, n = 10), model group (model mice without any treatment, n = 10), and K252a group (model mice treated with 100 µmol/kg TrkB-PLC/IP3 pathway inhibitor for 5 days before clysis, n = 10). The results showed that mice in the model and K252a groups, as compared with normal and control groups, had no significant changes in the levels and protein expressions of serum tumor necrosis factor-α (TNF-α) and TNF-γ in the colon tissues (P>0.05), and had a significant increase in disease activity index, colon mucosa damage index, tissue damage index scores, and levels and protein expressions of serum interleukin-4 (IL-4) and IL-8, but had a significant decrease in the level and protein expression of serum IL-10 (P<0.05). Mice in the model and K252a groups showed blocked enterocyte cycle progression, elevated apoptosis ratio, and significantly increased mRNA and protein expressions of Caspase3, Bax, FasL, and Fas, but significantly reduced mRNA and protein expressions of p-TrkB, PLC-γ1, IP3, and Bcl-2 (P<0.05). Moreover, intestinal inflammation and apoptosis induced by colitis in the K252a group became more aggravated by inhibiting the activity of TrkB-PLC/IP3 pathway. In conclusion, inhibition of TrkB-PLC/IP3 pathway can increase the expression of intestinal inflammatory factors and promote enterocyte apoptosis in mice with colitis.

Berberine promotes nerve regeneration through IGFR­mediated JNK­AKT signal pathway.

Berberine presents therapeutic ability for various central nervous system disorders, including Alzheimer's disease and cerebral ischemia. The present study investigated the role of berberine in nerve regeneration and analyzed the potential mechanism mediated by berberine in hippocampal pyramidal neurons. Reverse transcription­quantitative poylmerase chain reaction, western blot, TUNEL assay and immunofluorescence were used to analyze the therapeutic effects of berberine on nerve regeneration. Berberine treatment increased growth and viability of hippocampal pyramidal neurons. Berberine treatment inhibited apoptosis of hippocampal pyramidal neurons and increased apoptosis regulator Bcl­2 and Bcl­w expression. Neuroinflammation of tumor necrosis factor α, interleukin (IL)1ß, IL6 levels and autophagy­related proteins microtubule­associated proteins 1A/1B light chain 3B, autophagy related 16 like 1 and autophagy related 7 were downregulated by berberine treatment in hippocampal pyramidal neurons. Notably, study has found that berberine increased insulin-like growth factor receptor (IGFR) and decreased c­Jun N­terminal kinase (JNK) and protein kinase B (AKT) expression in hippocampal pyramidal neurons. IGFR antagonist abolished berberine­increased growth of hippocampal pyramidal neurons. In conclusion, these results indicate that berberine can promote nerve regeneration through IGFR­mediated JNK­AKT signal pathway.