Gastrointestinal malignant tumors are common worldwide,particularly gastric cancer(GC)and colorectal cancer(CRC),with complex and not fully understood molecular mechanisms behind their occurrence and progression.Treatment typically involves a comprehensive approach centered on surgery,which,despite achieving good outcomes,still faces challenges due to high recurrence rates and low survival rates impacting patient health.N6-methyladenosine(m6A)is the most abundant internal modification in mRNAs and plays a crucial role in regulating RNA post-transcriptional modifications and downstream functions.Fat mass and obesity-associated protein(FTO)was the first identified m6A demethylase capable of removing dynamic,reversible m6A modifications.During the development of gastrointestinal malignancies,FTO regulates the expression of specific genes,affecting tumor cell proliferation and metastasis;modulates the expression of tumor-related cytokines and immune-related molecules,influencing the tumor microenvironment;and plays a significant role in sensitivity and resistance to chemotherapy.FTO is upregulated in most types of GC,indicating poor prognosis.High FTO expression enhances GC cell migration and invasion,increases chemoresistance,promotes tumor stem cell proliferation and differentiation,and inhibits apoptosis,thus facilitating GC progression.In CRC,many studies show that FTO is upregulated in tissues and cells,promoting CRC progression by enhancing cell proliferation,migration,invasion,and resistance to chemotherapy.Low FTO expression can also elevate m6Am levels in CRC cell cytoplasmic mRNA,promoting tumor stem cell proliferation,differentiation,tumor formation,and increasing resistance.In contrast,high FTO expression inhibits tumor stem cell proliferation and differentiation.FTO is also upregulated in other gastrointestinal tumors like pancreatic and esophageal cancers,where high expression promotes progression and indicates poor prognosis.FTO has both promoting and inhibitory effects on liver and biliary malignancies.As research confirms FTO's widespread oncogenic role in the gastrointestinal tract,developing FTO inhibitors and related drugs offers new avenues for treating gastrointestinal malignancies.Currently identified agents like CS1,omeprazole,and mupirocin significantly inhibit CRC and GC progression by directly or indirectly suppressing FTO.Tumors can evade immune surveillance through FTO-mediated mechanisms,suggesting that blocking FTO-mediated immune escape and enhancing the antitumor effects of immune cells could provide treatment options for gastrointestinal malignancies.Targeting FTO in combination with immunotherapy to inhibit GC and CRC growth and metastasis and reduce resistance presents broad therapeutic prospects.

Objective:To investigate the risk factors for the occurrence and poor in-hospital prognosis in patients with peripartum cardiomyopathy (PPCM).Methods:The clinical data of 35 patients with PPCM and 35 healthy pregnant women in Xuanwu Hospital, Capital Medical University and Beijing Friendship Hospital Affiliated to Capital Medical University from January 2003 to January 2022 were retrospectively analyzed. The personal histories, laboratory examination, imaging examination, cardiac function outcome, etc were collected. According to the left ventricular ejection fraction (LVEF) at discharge, the patients with PPCM were divided into in-hospital recovery group (LVEF≥50%, 18 cases) and prolonged disease group (LVEF<50%, 17 cases). Multivariate Logistic regression analysis was used to analyze independent risk factors of poor in-hospital prognosis in patients with PPCM.Results:Among 35 patients with PPCM, the age was (29.81 ± 5.37) years old, 17 cases (48.57%) complicated with gestational hypertension, 6 cases (17.14%) complicated with gestational diabetes mellitus, 24 cases (68.57%) of New York Heart Association (NYHA) cardiac function classification was Ⅲ to Ⅳ class, and 4 cases died (11.43%). The gestational age in patients with PPCM was significantly shorter than that in healthy pregnant women: (36.26 ± 4.27) weeks vs. (38.54 ± 4.59) weeks, the rates of multiple pregnancy and gestational hypertension were significantly higher than those in healthy pregnant women: 17.14% (6/35) vs. 2.86% (1/35) and 48.57% (17/35) vs. 11.43% (4/35), and there were statistical differences ( P<0.05 or <0.01). Compared with hospital recovery group, the patients in protracted disease group had shorter gestational age, larger left ventricular end-diastolic diameter, higher serum creatinine, C-reactive protein and amino-terminal pro-brain natriuretic peptide (NT-proBNP), worse NYHA cardiac function classification, and there were statistical differences ( P<0.05 or <0.01); but there were no statistical difference in LVEF at the first diagnosis and troponin I between two groups ( P>0.05). Multivariate Logistic regression analysis result showed that elevated creatinine was an independent risk factor for poor in-hospital prognosis in patients with PPCM ( OR = 4.554, 95% CI 1.536 to 13.684, P = 0.018). Conclusions:The gestational hypertension may be a risk factor for PPCM. The gestational hypertension, earlier onset time, enlarged left ventricular end-diastolic diameter, high NT-proBNP, high C-reactive protein, high creatinine and high cardiac function NYHA classification may be risk factors for poor in-hospital prognosis in patients with PPCM; and elevated creatinine is an independent risk factor for poor in-hospital prognosis in patients with PPCM.

The Ly-6 and uPAR (LU) domain-containing proteins represent a large family of cell-surface markers. In particular, mouse Ly-6A/Sca-1 is a widely used marker for various stem cells; however, its human ortholog is missing. In this study, based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins, we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1. This gene, hereby named LY6A, reversely overlaps with a lncRNA gene in the majority of exonic sequences. We found that LY6A is aberrantly expressed in pituitary tumors, but not in normal pituitary tissues, and may contribute to tumorigenesis. Similar to mouse Ly-6A/Sca-1, human LY6A is also upregulated by interferon, suggesting a conserved transcriptional regulatory mechanism between humans and mice. We cloned the full-length LY6A cDNA, whose encoded protein sequence, domain architecture, and exon-intron structures are all well conserved with mouse Ly-6A/Sca-1. Ectopic expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell membrane. Collectively, these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms.
Humans ; Membrane Proteins/genetics* ; Pituitary Neoplasms/genetics* ; Biomarkers

Objective:To compare the influence of single and staged percutaneous coronary intervention (PCI) on long-term prognosis in patients with multi-vessel coronary artery disease.Methods:Using prospective research methods, 1 832 patients with multi-vessel coronary artery disease from January to December 2013 in Fuwai Hospital, Chinese Academy of Medical Sciences were selected. According to the time of PCI, the patients were divided into single PCI group (1 218 cases) and staged PCI group (614 cases). The patients were followed up for 2 years, the primary endpoint was major cardiovascular and cerebrovascular event (MACCE), including target vessel-related myocardial infarction (TV-MI), target vessel-related revascularization (TVR), cardiogenic death and stroke, and the secondary endpoint was stent thrombosis. The propensity score matching (PSM) was applied to balance the discrepancies between 2 groups, and the baseline and follow-up data were compared. The Kaplan-Meier survival curves were drawn to evaluate the survival rates events; multifactor Cox proportional risk regression was used to analyze whether staged PCI was an independent risk factor for the endpoint events.Results:The in-hospital stay, duration of procedure and synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score in single PCI group were significantly lower than those in staged PCI group: (5.54±3.09) d vs. (9.50±4.06) d, (43.12±28.55) min vs. (79.54±44.35) min, (14.04±7.63) scores vs. (18.51±7.79) scores, and there were statistical differences ( P<0.01); there were no statistical difference in complete revascularization rate and SYNTAX score after PCI between 2 groups ( P>0.05). Based on 2-year follow-up, the incidences of TV-MI and stent thrombosis in staged PCI group were significantly higher than those in single PCI group: 2.1% (13/614) vs. 0.5% (6/1 218) and 2.0% (12/614) vs. 0.4% (5/1 218), and there were statistical differences ( P<0.01). Kaplan-Meier survival curves analysis results showed that the event-free survival rates of TV-MI and stent thrombosis in single PCI group were better than those in staged PCI group (99.5% vs. 97.9% and 99.6% vs. 98.0%, P<0.01). Multifactor Cox proportional risk regression analysis results showed that staged PCI was an independent risk factor for stent thrombosis ( HR = 3.91, 95% CI 1.25 to 12.18, P = 0.019). After PSM, the incidences of TV-MI and stent thrombosis in staged PCI group were significantly higher than those in single PCI group: 2.1% (13/614) vs. 0.7% (4/614) and 2.0% (12/614) vs. 0.5% (3/614), and there were statistical differences ( P<0.05); Kaplan-Meier survival curve analysis results showed that the event-free survival rates of TV-MI and stent thrombosis in single PCI group were significantly higher than those in staged PCI group: (99.3% vs. 97.9% and 99.5% vs. 98.0%, P<0.05); multifactor Cox proportional risk regression analysis results showed that staged PCI was not an independent risk factor of stent thrombosis ( HR = 2.29, 95% CI 0.58 to 9.00, P = 0.234). Both before and after PSM, there were no evidences for interaction between the type of angina pectoris and staged PCI ( P>0.05). Conclusions:Although a seemingly increase exists in the incidence of TV-MI and stent thrombosis in the staged PCI group, staged PCI is an independent risk factor neither for MACCE and its components, nor for stent thrombosis. In addition single PCI reduces the in-hospital days and duration of PCI procedure, which may be a relatively reasonable approach to clinical practice.

Bisecting N-acetylglucosamine(GlcNAc),a GlcNAc linked to the core β-mannose resi-due via a β1,4 linkage,is a special type of N-glycosylation that has been reported to be involved in various biological processes,such as cell adhesion and fetal development.This N-glycan structure is abundant in human trophoblasts,which is postulated to be resistant to natural killer cell-mediated cytotoxicity,enabling a mother to nourish a fetus without rejection.In this study,we hypothesized that the human amniotic membrane,which serves as the last barrier for the fetus,may also express bisected-type glycans.To test this hypothesis,glycomic analysis of the human amniotic membrane was performed,and bisected N-glycans were detected.Furthermore,our pro-teomic data,which have been previously employed to explore human missing proteins,were ana-lyzed and the presence of bisecting GlcNAc-modified peptides was confirmed.A total of 41 glycoproteins with 43 glycopeptides were found to possess a bisecting GlcNAc,and 25 of these gly-coproteins were reported to exhibit this type of modification for the first time.These results provide insights into the potential roles of bisecting GlcNAc modification in the human amniotic membrane,and can be beneficial to functional studies on glycoproteins with bisecting GlcNAc modifications and functional studies on immune suppression in human placenta.

Objective To explore the predictive value of CT image texture analysis for early enlargement of hypertensive intracerebral hemorrhage.Methods One hundred and eight patients with hypertensive intracerebral hemorrhage were divided into enlarged hematoma group (positive group)and non-enlarged hematoma group (negative group),according to whether the volume of hematoma on 24 h follow up CT scan was more than 30% or 6 mL of the baseline CT.Phillis Radiomics Tool V93 software was used to segment the hematoma on CT plain scan images of two groups,four features of first-order and three of gray-level co-occurrence matrix (GLCM),thirteen of gray-level size zone matricx (GLSZM)and eleven of gray-level run-length matricx (GLRLM)were obtained.The differences of thirty-one texture features between the two groups were compared.The ROC curves of the features with statistical differences were analyzed.The independent predictors of early enlargement of intracerebral hemorrhage were screened by Logistic multivariate regression model.Results Among the one hundred and eight patients,twenty-eight were positive group and eighty were negative group.Skewness and long run low gray-level emphasis (LRLGE)in positive group were significantly higher than those in negative group (P＜0.05).There was no significant difference in the remaining twenty-nine features between the two groups (P＞0.05).ROC curve analysis showed that the AUC of Skewness,LRLGE and their combined diagnosis were 0.634,0.814 and 0.828,respectively.The independent variables were screened by stepwise regression analysis.The LRLGE (OR＝1.238,95%CI＝1.009－1.51 9,P＜0.05)was selected as the regression model, suggesting that LRLGE was an independent predictor of the early enlargement of intracerebral hemorrhage.Conclusion Texture analysis of CT images is helpful to predict the early enlargement of hypertensive intracerebral hemorrhage,and LRLGE based on GLRLM algorithm can be used as an independent predictor.

Objective ToassessthevalueofGdGEOBGDTPAenhancedT1ρimaginginevaluatingtheseverityandinflammation gradeinnonalcoholicsteatohepatitis(NASH)rabbitsmodel.Methods NASH modelswereestablishedin26adultrabbitsbyfeeding withthehighGfat,highGcholesteroldietinavarieddurations (0,4,8,12 weeks).T1ρ,T1ρinthehepatobiliaryphase (HBP)and changeofT1ρ(Δ%)werecomparedamongthedifferentgroupswhichweredeterminedbydifferentnonGalcoholicfattyliverdisease activityscore(NAS)andinflammationgrades.SpearmancorrelationanalysiswasusedtoassessthecorrelationsofT1ρ,T1ρ(HBP) withNASscoresandinflammationgrades.ROCcurvewasperformedtoevaluatethediagnosticvalueofT1ρ,T1ρ(HBP)inpredicting NASHandadvancedinflammation.Results T1ρandT1ρ(HBP)werepositivelyassociatedwithNASandinflammationscores.The differencesofT1ρ(HBP)amongNASH,nonalcoholicfattyliver(NAFL)andnormalliverwerestatisticallysignificant(P＜0.05). T1ρ(HBP)wassignificantlydifferentintherabbitswithgrade3inflammationfromintherabbitswithgrade0,grade1andgrade2 inflammation (P＜0.05).AUCsofT1ρandT1ρ(HBP)fordifferentiatingNASH were0.849and0.949,respectively.AUCofT1ρand T1ρGHBPfordiagnosinggrade2andgrade3inflammationwere0.925and0.922,respectively.Fibrosisandinflammationwerethe mainindependentfactorsaffectingT1(HBP).Conclusion GdGEOBGDTPAenhancedT1ρimagingcanreflecttheseverityofNASH anddegreeofinflammation.T1ρ(HBP)mightbeamoresuperiornoninvasiveimagingbiomarkerthannonGenhancedT1ρforassessmentof NASHactivityandinflammationgrading.

Objective: To evaluate the relationship between platelet distribution width(PDW) and the extent of coronary artery disease and 2-year outcome in patients received percutaneous coronary artery intervention(PCI) because of stable coronary artery disease(SCAD). Methods: We consecutively enrolled 4 293 patients who received PCI because of SCAD in Fuwai Hospital from Jan 2013 to Dec 2013, patients were followed up for 2 years. Patients were divided into three groups according to tertiles values of PDW as follows: PDW≤11.4%(1 402 patients), 11.4%12.9% (1 450 patients). Major adverse cardiovascular and cerebrovascular events (MACCE) were defined as the occurrence of death, myocardial infarction, target vessel revascularization, intra stent thrombosis and stroke during follow-up. Multivariable logistic regression was used to evaluate the relationship between PDW and the extent of CAD. Multivariable Cox regression was used to evaluate the relationship between PDW and prognosis of SCAD patients. Results: PDW was associated with diabetes mellitus, body mass index, red cell distribution width, mean platelet volume (MPV), platelet counts and glycosylated haemoglobin (P<0.05), but not associated with age, sex, estimated glomerular filtration rate (P>0.05). PDW was not correlated with the extent of CAD(P=0.990), SYNTAX score(P=0.721), no-reflow phenomenon after PCI(P=0.978). Multivariable logistic regression also showed no relationship between PDW and extent of CAD (OR=0.994, 95%CI 0.961-1.029, P=0.73). PDW was found to be an independent risk factor of 2-year cardiac death (HR=1.242, 95%CI 1.031-1.497, P=0.022), but was not an independent risk factor of all-cause death and MACCE. Conclusions PDW is not related with the extent of coronary artery disease. PDW is an independent risk factor of 2-year cardiac death, but is not an independent risk factor of all-cause death and MACCE in this patient cohort.

Objective:To investigate the effects of icaritin(ICT)on the proliferation and osteogenic differentiation of rat bone mar-row stromal cells(rBMSCs).Methods:rBMSCs were cultured from the bone marrow of SD rats and identified by multilineage differ-entiation assays.3,6 and 9 days after the treatment of rBMSCs of passage 4 by ICT at 1 0 -9 ,1 0 -8 ,1 0 -7 ,1 0 -6 and 1 0 -5 mol/L re-spectively,the proliferation and differentiation of the cells were examined by cck-8 and alkaline phosphatase (ALP)activity assay kit respectively.The calcium nodule formation was observed by alizarin red(AR)staining 21 days after 1 0 -9 mol/L ICT treatment. Results:Primary rBMSCs showed the typical spindle-like shape with attachment growth.rBMSCs could be induced to osteogenic and adipogenic differentiation.The proliferation of rBMSCs was inhibited but ALP activity was enhanced by ICT.1 0 -9 mol/L ICT in-cresed calcium nodule formation.Conclusion:ICT can dose-dependently inhibit the proliferation,but promote the osteogenic differ-entiation of rBMSCs.

Objective: To explore aspirin resistance (AR) phenomenon in patients with coronary artery disease (CAD) for secondary prevention and to study the relationships between AR and COX1, COX2, TBXA2R gene polymorphisms. Methods: A total of 2881 CAD patients taken aspirin (100 mg/day) in 7 consecutive days were enrolled. Among them, 2 groups were established as AR group, n=166 and Control group, n=200 aspirin sensitive patients. Platelet aggregation function was induced by arachidonic acid (AA), COX1, COX2 and TBXA2R gene polymorphisms were examined by polymerase chain reaction-restricted fragment length polymorphisms (PCR-RFLP) method. Results: The occurrence rate of AR was 5.76% (166/2881). There were 8 tagSNPs locus in 3 genes as in COX1:(rs3842788), (rs4273915), (rs7866582); in: COX2 (rs3218625); in TBXA2R: (rs2238630), (rs2238631), (rs2238633), (rs3786989). The frequencies of wild type, heterozygous genotype and homozygous genotype were similar between 2 groups. Conclusion: The incidence rate of AR is not high in CHD patients with regular aspirin medication; single nucleotide gene polymorphisms of COX1, COX2 and TBXA2R have no obvious correlation to AR.