The polymerase 1 and transcript release factor (PTRF)-cytoplasmic phospholipase A2 (cPLA2) phospholipid remodeling pathway facilitates tumor proliferation in glioma. Nevertheless, blockade of this pathway leads to the excessive activation of oncogenic receptors on the plasma membrane and subsequent drug resistance. Here, CD26/dipeptidyl peptidase 4 (DPP4) was identified through screening of CRISPR/Cas9 libraries. Suppressing PTRF-cPLA2 signaling resulted in the activation of the epidermal growth factor receptor (EGFR) pathway through phosphatidylcholine and lysophosphatidylcholine remodeling, which ultimately increased DPP4 transcription. In turn, DPP4 interacted with EGFR and prevented its ubiquitination. Linagliptin, a DPP4 inhibitor, facilitated the degradation of EGFR by blocking its interaction with DPP4. When combined with the cPLA2 inhibitor AACOCF3, it exhibited synergistic effects and led to a decrease in energy metabolism in glioblastoma cells. Subsequent in vivo investigations provided further evidence of a synergistic impact of linagliptin by augmenting the sensitivity of AACOCF3 and strengthening the efficacy of temozolomide. DPP4 serves as a novel target and establishes a constructive feedback loop with EGFR. Linagliptin is a potent inhibitor that promotes EGFR degradation by blocking the DPP4-EGFR interaction. This study presents innovative approaches for treating glioma by combining linagliptin with AACOCF3 and temozolomide.

Objective: To investigate cardiovascular disease (CVD) prevention status among residents with intra-urban migration in Central China, so as to provide insights into targeted prevention and control of CVD. Methods: Basic data of residents aged 35 to 75 years who participated in Early Screening and Comprehensive Intervention Project for CVD high-risk populations in Central China from September 2015 to August 2020 were collected. According to birth place, type of registered residence and current residence, residents were divided into four groups: local residents in old urban area, local residents in new urban area, other urban migrants and other rural migrants. The status of CVD primary and secondary prevention, were analysed by using a robust Poisson regression model. Results: A total of 76 513 residents were recruited, including 29 420 males (38.45%) and 47 093 females (61.55%), and had a mean age of (56.36±9.84) years. There were 45 087 (58.93%) local residents in old urban area, 23 868 (31.19%) local residents in new urban area, 5 668 (7.41%) other urban migrants and 1 890 (2.47%) other rural migrants. After adjusting for variables such as age, gender and educational level, the results of robust Poisson regression analysis showed that compared with local residents in old urban area, local residents in new urban area had lower compliance rates of non- or moderate-drinking (RR=0.987, 95%CI: 0.975-1.000) and healthy diet (RR=0.535, 95%CI: 0.365-0.782), lower proportion of using aspirin as primary prevention in CVD high-risk population (RR=0.616, 95%CI: 0.511-0.741), lower awareness (RR=0.873, 95%CI: 0.782-0.974) and control rates (RR=0.730, 95%CI: 0.627-0.849) of hypertension; other urban migrants had higher compliance rate of non-smoking (RR=1.045, 95%CI: 1.017-1.075); other rural migrants had lower proportion of using aspirin as primary prevention in CVD high-risk population (RR=0.826, 95%CI: 0.707-0.966). Conclusion The CVD primaryprevention among local residents in new urban area is relatively poor among four groups of residents in Central China, and key interventions are needed.

BACKGROUND: With age and blood pressure increasing, the damaged elastic membrane induced by degenerative vascular matrix results in calcium and collagen deposition, and finally expanded large arteries and aortas are easy to cause arteriosclerosis. OBJECTIVE: To compare the rheological properties of the common carotid artery in the youth and elderly, thus providing a basis for the study on the pathogenesis of atherosclerosis of the common carotid artery. METHODS: Common carotid arteries were respectively removed from the young and elderly cadavers. Ten samples from each group were randomly selected, and subjected to stress relaxation and creep tests. Meanwhile, one sample from each group was selected for histological observation. RESULTS AND CONCLUSION: The stress at 7200 s in the young group was significantly decreased compared with the elderly group (P < 0.05). The strain at 7200 s in the young group was significantly increased compared with the elderly group (P < 0.05). Scanning electron microscope observed that in the elderly group, there were lipid plaques and foam cell accumulation; the internal elastic lamina and middle elastic plate presented with degeneration, rupture and disintegration; and there were abundant plaques and inflammatory cells in the intimal and media, which characterized as atherosclerosis. While no lipid plaques were found in the young group. These results indicate that the elastic fibers and collagen fibers in the common carotid artery arrange in disorder as age increases, and the rheological properties are also changed.

Objective To detect the changes in vertebral marrow fat fraction (MFF) using T2 *-corrected water-fat MRI and to analyze the relationships between MFF with bone biomarkers of non-dialysis chronic kidney disease (CKD).Methods 78 CKD patients were divided into five groups according to the eGFR and underwent water/fat MRI to obtain MFF.The reliability of MFF measurements by two radiologists was assessed with intra-class correlation coefficient (ICC).Serum calcium,phosphorus,alkaline phosphatase,osteocalcin,intact parathyroid hormone and 25(OH)D3 were determined.Results Mean CV for MFF measurements reproducibility was 2.37％.The inter-observer agreement for MFF was excellent (ICC=0.901).The ICC for each intra-observer agreement was excellent (ICC=0.959 and 0.948,respectively).There were statistical differences in MFF among five groups of CKD.Changes of MFF were earlier than those of serum calcium,phosphorus,parathyroid hormone,alkaline phosphatase and osteocalcin.MFF was positively correlated with serum phosphorus (r =3.011,P =0.003),parathyroid hormone (r=3.852,P＜0.001),and negatively associated with calcium (r=-2.767,P=0.017),25(OH)D3 (r=6.032,P＜0.001),eGFR (r=-5.104,P＜0.001),respectively.Multivariable regression analysis showed MFF was negatively correlated with 25(OH)D3(Sβ=-0.343)and eGFR(S(S=-0.284,P＜0.001).Conclusion CKD patients had higher marrow fat.T2 *-corrected water fat MRI could serve as a useful tool to quantify marrow fat content for CKD patients.

OBJECTIVES: To explore the genetic variation sites of caveolin （CAV） and their correlation with sudden unexplained death （SUD）. METHODS: The blood samples were collected from SUD group （71 cases）, coronary artery disease （CAD） group （62 cases） and control group （60 cases）, respectively. The genome DNA were extracted and sequencing was performed directly by amplifying gene coding region and exon-intron splicing region of CAV1 and CAV3 using PCR. The type of heritable variation of CVA was confirmed and statistical analysis was performed. RESULTS: A total of 4 variation sites that maybe significative were identified in SUD group, and two were newfound which were CAV1： c.45C>T （T15T） and CAV1：c.512G>A （R171H）, and two were SNP loci which were CAV1：c.246C>T （rs35242077） and CAV3：c.99C>T （rs1008642） and had significant difference （P<0.05） in allele and genotype frequencies between SUD and control groups. Forementioned variation sites were not found in CAD group. CONCLUSIONS The variants of CAV1 and CAV3 may be correlated with a part of SUD group.
Caveolins/genetics* ; Coronary Artery Disease ; Death, Sudden/etiology* ; Exons ; Genotype ; Humans ; Male ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide

OBJECTIVE:To extract and identify the volatile components of the roots of Polyalthia nemoralis,and to evaluate its biological activity in vitro. METHODS:Supercritical CO2 extraction (SFE-CO2) was performed to extract volatile compounds from the roots of P. nemoralis,and the volatile components were separated and determined by GC-MS. Human hepatic cancer Huh-7 cells were cultured with 0(blank control),5,10,20,30,40 and 50 μg(medicinal material)/ml extract for 24 h,and then MTT assay was used to detect the inhibitory effect of the extracts on cells. Relative cell viability and IC50 were calculated. The an-ti-bacterial activities of extract to Staphylococcus aureus,Methicillin-resistant Staphylococcus aureus,Enterococcus faecalis and oth-er strain were determined by Kirby-bauer method and broth dilution method. RESULTS:Forty compounds were identified from the SFE-CO2 extracts from the roots of P. nemoralis. The main constituents were(Z,Z,Z)-9,12,15-octa-decatrien-1-ol,glycerin,cinna-maldehyde,n-hexadecanoic acid and eugenol. Compared with blank control group,SFE-CO2 extracts from the roots of P. nemoralis 5 μg(medicinal material)/ml and above showed significant inhibitory effect on cell growth(P<0.05),and the inhibitory effect was strengthened as the concentration of extracts increased,IC50 values was 5.2 μg(medicinal material)/ml. However,the supercritical extract didn't showed antibacterial activity against three microorganisms in 2 kinds of antibacterial tests. CONCLUSIONS:SFE-CO2 and GC-MS method can effectively extract and identify volatile components of the roots of P. nemoralis,and supercritical extracts can inhibit the viability of cells but have no antibacterial activity.