Int J Med Sci
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The incidence of cutaneous melanoma (CM) increased since the 1970s, and also along with an unfavorable prognosis. CM patients have been verified benefits from immunotherapy, and granzymes (GZMs) comprise more than 90% of the cytolytic granules secreted by cytotoxic T lymphocytes and nature killer cell. Therefore, it is essential to evaluate the prognostic value of GZMs in CM. ⋯ A higher tumor mutation burden was observed in low-risk group, especially for the mutation of BRAF. The protect function of GZMK was confirmed by CM cell lines, overexpression of GZMK in A375 and G361 cells suppresses cell proliferation, migration, but not cell apoptosis. All in all, we revealed the prognostic value of GZMs in CM patients, which could also act as a predicted value for the selection of responders of anti-PD-1 immunotherapy.
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Background: Mucopolysaccharidoses (MPSs) are lysosomal storage disorders wherein glycosaminoglycans accumulate because the enzymes that degrade them are insufficient. The earliest symptoms, which are the main reasons for seeking consultation, are otorhinolaryngological and commonly occur in MPS I, II, IV, and VI. This retrospective study aimed to determine the occurrence of otorhinolaryngological manifestations in MPS patients in Taiwan and to analyze the prognosis of surgical intervention, including its effect on symptoms. ⋯ Moreover, 76% of the patients underwent ear, nose, and throat (ENT) surgery, including adenoidectomy, tonsillectomy, tympanostomy with ventilation tube insertion, tracheotomy, and supraglottoplasty. Conclusions: MPS patients had a high incidence of ENT problems. ENT surgery reduced the severity of hearing loss, degree of symptoms related to upper airway obstruction, and severity of respiratory tract and otological infections of patients with MPS.
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Focused ultrasound (FUS) is used to locally and transiently induce blood-brain barrier (BBB) permeability, allowing targeted drug delivery to the brain. The purpose of the current study is to evaluate the potential of Vasculotide to accelerate the recovery of the BBB following FUS disruption in the TgCRND8 mouse model of amyloidosis, characteristic of Alzheimer's disease (AD). Accelerating the restoration of the BBB post-FUS would represent an additional safety procedure, which could be beneficial for clinical applications. ⋯ BBB permeability was assessed by gadolinium up to 20-hours post-FUS, demonstrating 87% closure in Vasculotide treated TgCRND8 mice, as opposed to 52% in PBS treated TgCRND8 mice, 58% in PBS treated non-transgenic mice, and 74% in Vasculotide treated non-transgenic mice. In both TgCRND8 mice and non-transgenic littermates the BBB was impermeable to Evans blue dye at 24-hours post-FUS. Conclusion: Vasculotide reduces the pressure required for microbubble ultra-harmonic onset for FUS-induced BBB permeability and it accelerates BBB restoration in a mouse model of amyloidosis, suggesting its potential clinical utility to promote vascular health, plasticity and repair in AD.
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Background: We investigated the extent of growth of microorganisms with simultaneous administration of lipid emulsions with infusions for Total Parenteral Nutrition (TPN), assuming that the lipid emulsions contaminated with microorganisms are stagnant in a closed-type infusion device. We also investigated if bacterial growth can be prevented in the infusion device by flushing the inside of the infusion device with saline solution after the administration of lipid emulsion from the side tube in vitro setting. Methods: We made a preparation by adding Escherichia coli to the lipid emulsion and started the infusion simultaneously with the infusion solution for TPN and lipid emulsion with the piggyback method. ⋯ Conclusions: We found that if E. coli was present in the closed-type infusion device, it would multiply. We also found that the number of viable bacteria varied according to the variety and internal structure of the closed-type infusion device as well as the liquid volume used for flushing, although flushing can prevent the growth of microorganisms. Proper management and manipulation of infusion is required to prevent infection.
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Background: The cell division cycle-associated (CDCA) protein family plays a pivotal role in the regulation of the cell cycle during tumorigenesis and predicts the prognosis of tumors, but an analysis of these proteins in pancreatic adenocarcinoma (PAAD) is still lacking. Methods: Oncomine and GEPIA were used to observe the expression and prognostic value of eight CDCAs in pan-cancer. Univariate Cox analysis of single CDCAs and multivariate Cox analysis of all eight CDCAs were performed to evaluate the integrated prognostic value of CDCAs, and the results are displayed as hazard ratios (HRs) and 95% confidence intervals (95% CIs). ⋯ After comparing high- and low-risk groups separated by CDCA risk scores, the activated pathways were revealed and included the cell cycle, DNA repair, P53, MYC-targets, E2F-targets and PI3K pathways. Conclusion: CDCAs can predict the OS prognosis of PAAD patients. The cell cycle, DNA repair, E2F, P53 and PI3K signaling pathways, in which CDCAs are involved, impact the tumorigenesis of PAAD.