The primary purpose of these research was to demonstrate the preventive effect of IMA on lipopolysaccharide (LPS)-induced inflammation in acute lung injury(ALI) mouse models and Human umbilical vascular endothelial cells (HUVECs). LPS stimulation for 24h to induce ALI and inflammation of cells. The pathological results of lungs was evaluated by W/D ratio, pulmonary vascular permeability measurement and immunohistochemistry of myeloperoxidase(MPO). Cell viability was measured using CCK8 assay. Expression of pro-inflammatory mediators was analyzed by RT-PCR and ELISA. The protein level was analyzed by Western blot. The structure of cell junction was detected by immunofluorescence. IMA dose-dependently improved pulmonary pathological damage induced by LPS, reduced the lung wet/dry weight ratio and MPO expression in lung tissue. IMA decreased bronchoalveolar lavage fluid (BALF) inflammatory cell count, as well as the release of tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemotactic protein 1 (MCP-1) in blood. Pretreatment with IMA in HUVECs significantly attenuated LPS-induced actin stress fiber formation and VE-cadherin disruption. In addition, IMA down-regulated the mRNA abundances of Vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), interleukin-1B (IL-1β), IL-6 and TNF-α expression, the phosphorylation of protein p-p65, p-IκBα, p-p38, p-ERK and p-JNK induced by LPS were attenuated after IMA treatment in vivo and in vitro. In summary, IMA modulate of NF-κB and MAPK signaling pathways as well as the production of pro-inflammatory cytokines to prevent cellular damage due to LPS infection. These results indicate that in the treatment of LPS-induced acute lung injury, IMA could be a potential modulator.
2Batch inconsistency is a major problem when applying LC-MS based untargeted 1 3 metabolomics in real-time analysis situation such as clinical diagnosis or health monitoring.
4And inefficiency of collecting MS2 is a major problem for metabolite identification. Here, we 1 5 developed a reference-feature based quantification and identification strategy (RFQI). In 1 6 RFQI, samples are individually profiled using a pre-fixed reference feature table.
7Quantification results show that RFQI improves features'overlap rate and reduce variance 1 8 across batches significantly in real-time-analysis mode, and can find more than 4-fold 1 9 numbers of features. Besides, RFQI collects MS2 from consecutive increasing samples for 2 0 metabolite identification of pre-fixed features, thus it can effectively compensate for the poor 2 1 efficiency of MS2 collection in data-dependent acquisition mode. In summary, RFQI can 2 2 make full advantage of consecutive increasing samples in real-time analysis situation, both for 2 3 quantification and identification. 2 4 Key words: batch effect, LC-MS based untargeted metabolomics, metabolite identification 2 5 2 6 2 7
Objective: Late post-pancreatoduodenectomy hemorrhage (LPPH) is associated with a significant increase in perioperative mortality. It is of great significance to explore effective treatment methods for severe LPPH patients.
Methods: Between 2014 and 2021, 224 pancreatoduodenectomies were performed, and 14 patients had a late hemorrhage (occurring >24 h postoperatively). The clinicopathological variables and treatments related to hemorrhage were investigated.
Results: Out of the 14 LPPH patients, 6 had grade B hemorrhage and 8 had grade C hemorrhage. There were 11 cases of comorbid pancreatic fistula, 5 cases of biliary fistula, and 7 cases of abdominal infection. The median time to first hemorrhage after surgery was 9 days. Of the 6 grade B LPPH patients, 4 underwent conservative treatment, 1 underwent transarterial embolization (TAE), and 1 underwent local suturing at the bleeding site for hemostasis. Of the 8 grade C LPPH patients, One patient without pancreatic fistula and abdominal infection was given conservative treatment after no bleeding was found by digital subtraction angiography examination. The other 7 patients had comorbid pancreatic fistula, of which 5 had comorbid abdominal infection, 3 had comorbid biliary fistula, and all 7 patients underwent total pancreatectomy of the residual pancreas. Three of these patients simultaneously underwent endovascular treatment. All patients recovered and were discharged, with a mortality of 0%.
Conclusion: Total pancreatectomy of the residual pancreas is safe and feasible in grade C LPPH patients with comorbid pancreatic fistula, biliary leakage, or abdominal infection.
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