Novel lactylation-related signature to predict prognosis for pancreatic adenocarcinoma

BACKGROUND Lactate,previously considered a metabolic byproduct,is pivotal in cancer progression and maintaining the immunosuppressive tumor microenvironment.Further investigations confirmed that lactate is a primary regulator,introducing recently described post-translational modifications of histone and non-histone proteins,termed lysine lactylation.Pancreatic adenocarcinomas are characterized by increased glycolysis and lactate accumulation.However,our understanding of lactylation-related genes in pancreatic adenocarcinomas remains limited.AIM To construct a novel lactylation-related gene signature to predict the survival of patients with pancreatic cancer.METHODS RNA-seq and clinical data of pancreatic adenocarcinoma(PDAC)were obtained from the GTEx(Genotype-Tissue Expression)and TCGA(The Cancer Genome Atlas)databases via Xena Explorer,and GSE62452 datasets from GEO.Data on lactylation-related genes were obtained from publicly available sources.Differential expressed genes(DEGs)were acquired by using R package“DESeq2”in R.Univariate COX regression analysis,LASSO Cox and multivariate Cox regressions were produced to construct the lactylation-related prognostic model.Further analyses,including functional enrichment,ESTIMATE,and CIBERSORT,were performed to analyze immune status and treatment responses in patients with pancreatic cancer.PDAC and normal human cell lines were subjected to western blot analysis under lactic acid intervention;two PDAC cell lines with the most pronounced lactylation were selected.Subsequently,RT-PCR was employed to assess the expression of LRGs genes;SLC16A1,which showed the highest expression,was selected for further investigation.SLC16A1-mediated lactylation was analyzed by immunofluorescence,lactate production analysis,colony formation,transwell,and wound healing assays to investigate its role in promoting the proliferation and migration of PDAC cells.In vivo validation was performed using an established tumor model.RESULTS In this study,we successfully identified 10 differentially expressed lactylation-related genes(LRGs)with prognostic value.Subsequently,a lactylation-related signature was developed based on five OS-related lactylationrelated genes(SLC16A1,HLA-DRB1,KCNN4,KIF23,and HPDL)using Lasso Cox hazard regression analysis.Subsequently,we evaluated the clinical significance of the lactylation-related genes in pancreatic adenocarcinoma.A comprehensive examination of infiltrating immune cells and tumor mutation burden was conducted across different subgroups.Furthermore,we demonstrated that SLC16A1 modulates lactylation in pancreatic cancer cells through lactate transport.Both in vivo and in vitro experiments showed that decreasing SLC16A1 Level and its lactylation significantly inhibited tumor progression,indicating the potential of targeting the SLC16A1/Lactylation-associated signaling pathway as a therapeutic strategy against pancreatic adenocarcinoma.CONCLUSION We constructed a novel lactylation-related prognostic signature to predict OS,immune status,and treatment response of patients with pancreatic adenocarcinoma,providing new strategic directions and antitumor immunotherapies.

Feasibility and efficacy of endoscopic purse-string suture-assisted closure for mucosal defects induced by endoscopic manipulations

BACKGROUND Large or transmural defects induced by gastrointestinal endoscopic manipulations are difficult to close,although complete closure is recommended for better recovery.Endoscopic purse-string assisted suturing(EPSS)has been used in clinical practice and has proven to be an effective and safe technique for the closure of large mucosal defects.However,details regarding the efficacy of endoscopic pre-purse-string suture(P-EPSS)are unknown,especially that it offers several advantages over conventional EPSS(C-EPSS).AIM To elucidate the outcomes of EPSS-assisted closure in different clinical situations,and evaluate the efficacy of P-EPSS.METHODS This retrospective observational study included a total of 180 patients who underwent closure assisted by P-EPSS(n=63)or C-EPSS(n=117)between July 2014 and June 2020.The P-EPSS and C-EPSS groups were compared and the intergroup differences in aspects such as the lesion size,location,and morphology,incidence of complete closure,intraoperative perforation,and delayed adverse events were evaluated.Data on the features and clinical course of cases with adverse events were collected for further analysis.RESULTS Patients with lesion size larger than 3 cm,lesions located at the fundus of stomach,or submucosal tumors originating from the deep mucosa were more likely to undergo P-EPSS-assisted closure.The P-EPSS group showed a significantly higher proportion of intraoperative perforation(56%vs 17%)and a much shorter procedure time(9.06±6.14 min vs 14.84±7.25 min).Among adverse events,the incidence of delayed perforation(5%vs 4%;P=0.82)and delayed bleeding(3%vs 4%;P=0.96)did not differ significantly between the groups.Multivariate analysis revealed that lesions with incomplete closure[odds ratio(OR)=21.33;95%confidence interval(CI):5.45-83.45;P<0.01]or size greater than 3 cm(OR=3.14;95%CI:1.08-9.18;P=0.039)showed a statistical tendency to result in an increase in delayed adverse events.CONCLUSION The present study revealed that EPSS could achieve secure complete closure of mucosal defect.PEPSS could shorten the procedure and yield complete closure of mucosal defects.Rather than closure-type selection,incomplete closure or lesion size larger than 3 cm were associated with worse outcomes.

Potential use of actigraphy to measure sleep in monkeys: comparison with behavioral analysis from videography

DEAR EDITOR,Since the epoch-making observations of circadian rhythm in Mimosaceae plants,sleep has been investigated for centuries(de Mairan,1729;Du Monceau,1758).As a natural and reversible state,sleep is marked by reduced responsiveness to external stimuli,relative inactivity,and loss of consciousness.Although reduced responsiveness could potentially introduce significant danger to survival,nearly all animals in nature sleep.

Measurement of Mucosal Thickness in Denture-bearing Area of Edentulous Mandible

Background： The thickness of the alveolar mucosa influences the probability of the occurrence of denture-induced irritations. Thick denture-supporting tissues offer relief from mucosal tenderness and ulcers; however, the uniformity of the thickness across the entire mandibular alveolar mucosa cannot be accurately determined in edentulous patients. This study aimed to assess the mucosal thickness of the denture-bearing area in the edentulous mandible. Methods： Twenty-seven edentulous patients underwent cone-beam computed tomography scanning, wherein the patients wore a record base to retract soft tissues away from the alveolar mucosa. The measured regions were the central incisor （1C）, lateral incisor （1L）, canine （Ca）, first premolar （P 1）, second premolar （P2）, first molar （M 1）, and second molar （M2） regions. The thickness was measured in the alveolar ridge crest （T）, buccal （B1-B4）, and lingual （L I-L4） alveolar ridge mucosa. The average thickness of the mucosa at buccal sides （B） and lingual sides （L） were also assessed. Results： The differences in the mucosal thickness between the left and right sides were not significant. In the Ca-M2 regions, T was the thickest, and L3 was the thinnest of all the measured points in the same regions. L was significantly less than B in posterior regions （P 〈 0.01 ）. On the other hand, M2 at L4 was thinnest of all the measured regions from Ca to M2 （P 〈 0.01）, and was thicker than IC, IL, P1, and P2 at B2. Conclusions： Since the mucosal thickness of denture-bearing area in the edentulous mandible is not uniform; the tissue surface of the denture base or custom tray should be selectively relieved, which may reduce the risk of denture-induced irritations.