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OBJECTIVE@#This study investigated how the natural phytophenol and potent SIRT1 activator resveratrol (RSV) regulate necroptosis during Vibrio vulnificus (V. vulnificus)-induced sepsis and the potential mechanism.@*METHODS@#The effect of RSV on V. vulnificus cytolysin (VVC)-induced necroptosis was analyzed in vitro using CCK-8 and Western blot assays. Enzyme-linked immunosorbent assays and quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry and survival analyses were performed to elucidate the effect and mechanism of RSV on necroptosis in a V. vulnificus-induced sepsis mouse model.@*RESULTS@#RSV relieved necroptosis induced by VVC in RAW264.7 and MLE12 cells. RSV also inhibited the inflammatory response, had a protective effect on histopathological changes, and reduced the expression level of the necroptosis indicator pMLKL in peritoneal macrophages, lung, spleen, and liver tissues of V. vulnificus-induced septic mice in vivo. Pretreatment with RSV downregulated the mRNA of the necroptosis indicator and protein expression in peritoneal macrophages and tissues of V. vulnificus-induced septic mice. RSV also improved the survival of V. vulnificus-induced septic mice.@*CONCLUSION@#Our findings collectively demonstrate that RSV prevented V. vulnificus-induced sepsis by attenuating necroptosis, highlighting its potency in the clinical management of V. vulnificus-induced sepsis.
Assuntos
Animais , Camundongos , Necroptose , Resveratrol/uso terapêutico , Vibrio vulnificus , Sepse/tratamento farmacológico , Western BlottingRESUMO
Background/Aims@#A high-quality sample allows for next-generation sequencing and the administration of more tailored precision medicine treatments. We aimed to evaluate whether heparinized wet suction can obtain higher quality samples than the standard dry-suction method during endoscopic ultrasound (EUS)-guided biopsy of pancreatic masses. @*Methods@#A prospective randomized crossover study was conducted. Patients with a solid pancreatic mass were randomly allocated to receive either heparinized wet suction first or dry suction first. For each method, two needle passes were made, followed by a switch to the other method for a total of four needle punctures. The primary outcome was the aggregated white tissue length. Histological blood contamination, diagnostic performance and adverse events were analyzed as secondary outcomes. In addition, the correlation between white tissue length and the extracted DNA amount was analyzed. @*Results@#A total of 50 patients were enrolled, and 200 specimens were acquired (100 with heparinized wet suction and 100 with dry suction), with one minor bleeding event. The heparinized wet suction approach yielded specimens with longer aggregated white tissue length (11.07 mm vs 7.96 mm, p=0.001) and less blood contamination (p=0.008). A trend towards decreasing tissue quality was observed for the 2nd pass of the dry-suction method, leading to decreased diagnostic sensitivity and accuracy, although the accumulated diagnostic performance was comparable between the two suction methods. The amount of extracted DNA correlated positively to the white tissue length (p=0.001, Spearman ̕s ρ=0.568). @*Conclusions@#Heparinized wet suction for EUS tissue acquisition of solid pancreatic masses can yield longer, bloodless, DNA-rich tissue without increasing the incidence of adverse events (ClinicalTrials.gov. identifier NCT04707560).
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Background/Aims@#Endoscopic ultrasonography (EUS)-guided tissue acquisition requires a long learning curve. We aimed to compare the skill maturation curves between fine needle aspiration (FNA) and biopsy (FNB) for tissue acquisition. @*Methods@#The initial 60 procedures performed by the trainee endosonographer (30 FNA vs. 30 FNB) were consecutively enrolled. The difference in procedure performance was compared between the two groups. Learning curves were assessed. Twenty additional cases were subsequently enrolled to assess the consistency of performance in the FNB group. @*Results@#The FNB group acquired larger tissue samples (2.35 vs. 0.70 mm2; p<0.001) with lower blood content (p=0.001) and higher tissue quality (p=0.017) compared with the FNA group. In addition, the FNB group required less needle pass to establish a diagnosis (2.43 vs. 2.97; p=0.006). A threshold diagnostic sensitivity of ≥80% was achieved after performing 10 FNB procedures. The number of needle passes significantly decreased after conducting 20 FNB procedures (1.80 vs. 2.70; p=0.041). The diagnostic sensitivity and number of needle passes remained the same in the subsequent FNB procedures. By contrast, this skill maturation phenomenon was not observed after performing 30 FNA procedures. @*Conclusions@#In EUS-guided tissue acquisition, the FNB needle was more efficient and thus shortened the learning curve of EUSguided tissue acquisition in trainee endosonographers.
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Background/Aims@#Endoscopic ultrasonography (EUS)-guided tissue acquisition requires a long learning curve. We aimed to compare the skill maturation curves between fine needle aspiration (FNA) and biopsy (FNB) for tissue acquisition. @*Methods@#The initial 60 procedures performed by the trainee endosonographer (30 FNA vs. 30 FNB) were consecutively enrolled. The difference in procedure performance was compared between the two groups. Learning curves were assessed. Twenty additional cases were subsequently enrolled to assess the consistency of performance in the FNB group. @*Results@#The FNB group acquired larger tissue samples (2.35 vs. 0.70 mm2; p<0.001) with lower blood content (p=0.001) and higher tissue quality (p=0.017) compared with the FNA group. In addition, the FNB group required less needle pass to establish a diagnosis (2.43 vs. 2.97; p=0.006). A threshold diagnostic sensitivity of ≥80% was achieved after performing 10 FNB procedures. The number of needle passes significantly decreased after conducting 20 FNB procedures (1.80 vs. 2.70; p=0.041). The diagnostic sensitivity and number of needle passes remained the same in the subsequent FNB procedures. By contrast, this skill maturation phenomenon was not observed after performing 30 FNA procedures. @*Conclusions@#In EUS-guided tissue acquisition, the FNB needle was more efficient and thus shortened the learning curve of EUSguided tissue acquisition in trainee endosonographers.