Cytochrome P450 is a superfamily of metabolic enzymes and many of its members show tight correlation to the development of a variety of tumors.Cytochrome P450s are becoming novel research targets for personalized diagnosis and treatment because of its specialized enzymatic activity.This paper reviews the research progress and development of the cytochrome P 450 family in cancer field ,introduces the applications of cytochrome P 450 in clinical diagnosis and personalized medicine , looks into prospect research and application trend.

Clinical laboratory undergraduate program was switched from medicine to medical technology,the changes of personnel training program compel universities to adjust the curriculum system.Six domestic known as 211 universities who have laboratory and biology undergraduate programs were scrutinized and compared.Overall,the proportion of general courses covers 30％ of the credit hours in both clinical laboratory and biology programs.Ratio of these general education curriculums to professional core courses is as high as 1.90∶1 in clinical laboratory program.Also,there were very strong medical features and very weak medical technology characteristics in the basic course in clinical laboratory program.It suggested that the curriculum system nowadays cant conform to the new personnel training objective.A novel system from abroad should be adopted to optimize clinical laboratory program accord with the principles and concepts of wide caliber training model.

OBJECTIVETo study the expression of tumorigenesis-related stem cell markers Lgr5 and CD44 in different pathological types of intestinal polyps and their clinical significance in predicting tumorigenesis.

METHODSA total of 145 cases of colorectal polyps, adenomas and cancer tissues were obtained by colonoscopy biopsy. Immunohistochemistry was employed to detect the expression of Lgr5 and CD44 to analyze their relationship with the occurrence and prognosis of colon and rectal cancer.

RESULTSThe expression of CD44 in colon cancer tissue was 95.65%, significantly higher than that in normal mucosa (5%), inflammatory hyperplastic polyps (22.58%), tubular adenomatous polyps (55.26%) and villous polyps (75.76%) (P<0.05). The expression of Lgr5 in colorectal cancer was up to 95.65% while negative in normal colorectal tissue and was 16.12% in inflammatory hyperplastic tissues (P<0.05). The expression rate of Lgr5 was 86.84% in tubular adenoma and 93.94% in villous polyps, both comparable with that in colon cancer (P>0.05). Correlation analysis indicated that the expression of CD44 and Lgr5 were positively correlated with the progression of intestinal polyp tumorigenesis (rs=0.69377, P<0.0001; rs=0.81637, P<0.0001).

CONCLUSIONLgr5 and CD44 are highly expressed in colorectal cancer tissues in close correlation with the clinical and pathological features. The expression profiles of Lgr5 and CD44 represent a distinct feature to differentiate colorectal cancer from normal intestinal mucosa. Lgr5 is more closely correlated with tumor progression of polyps than CD44. This means detecting of the expression of Lgr 5 together with CD44 is important and necessary in clinical diagnosis of patients with early stage colorectal diseases such as polyps and their canceration.

Adult ; Aged ; Colorectal Neoplasms ; metabolism ; pathology ; Female ; Humans ; Hyaluronan Receptors ; metabolism ; Intestinal Polyps ; metabolism ; pathology ; Male ; Middle Aged ; Prognosis ; Receptors, G-Protein-Coupled ; metabolism ; Young Adult

Genetic Counseling ; United States

BACKGROUND:Studies have found that glucagon-like peptide-1 and its analogues have a significant neuroprotective effect,and some drugs have been applied to the clinical stage Ⅲ study of Alzheimer's disease.However,the mechanism of its neuroprotective effect is still unclear,which needs to be further explored and clarified. OBJECTIVE:To screen out the genes related to the pathogenesis of Alzheimer's disease and the related targets of semaglutide for the treatment of Alzheimer's disease based on bioinformatics and network pharmacology analyses,to identify the potential target genes by comprehensive analysis of the two and to verify them at the cellular level. METHODS:Using DisGeNET database,differentially expressed genes between Alzheimer's disease patients and healthy population were screened out.The chemical structure formula and two-dimensional structure diagram of semaglutide were obtained using PubChem online database.GO/KEGG enrichment analysis was performed using DAVID online database.A protein-protein interaction network was constructed by using the STRING database.The HPA database was used to determine the distribution characteristics of the target proteins in various human tissues.Finally,western blot was used to detect relevant protein expression in HT22 cells after semaglutide intervention. RESULTS AND CONCLUSION:With the dataset in DisGeNET database,3 374 differentially expressed genes between Alzheimer's disease patients and healthy people were obtained,and meanwhile,101 target genes of semaglutide potential drugs were obtained.There were 23 intersection genes between them.Ten key genes were identified based on the protein-protein interaction network,which were silent information regulator 1(SIRT1),CASP9,CCND1,CASP1,KEAP1,DLG4,CASP4,GRB2,GRIA1,and EDNRA.The results of GO gene functional annotation analysis of key genes showed that the positive regulatory activity of cysteine endopeptidase,the positive regulation of proteolysis,and the positive regulation of cysteine endopeptidase involved the cytoplasmic part of the apoptotic activity process;AMPA glutamate receptor complex,inflammatory complex,CARD domain binding,cysteine endopeptidase activity,and cysteine endopeptidase activity were involved in the apoptotic process.The results of KEGG signaling pathway analysis indicated that colorectal cancer,non-small cell carcinoma,and endometrial carcinoma were related to immune infiltration,inflammation and autophagic apoptosis.In addition,according to the association ranking of key genes and their distribution in different tissues of HPA online database,SIRT1 was identified as the most significant differential gene.The expression level of SIRT1 protein was significantly down-regulated in HT22 cells after β-amyloid protein 1-42 treatment,but it could be significantly increased after being treated with semaglutide.To conclude,SIRT1 may be a target gene for semaglutide in the treatment of Alzheimer's disease.

Objective:To investigate the influencing factors for total number, total volume, and total iron burden of cerebral microbleeds (CMBs) and the relationship between CMBs with cognitive impairment in end-stage renal disease (ESRD) using semi-automatic quantitative susceptibility mapping (QSM).Methods:The study was a cross-sectional study. Clinical and imaging data of 46 ESRD patients with≥1 CMBs who attended Tianjin First Central Hospital from November 2018 to August 2022 were retrospectively analyzed. There were 26 males and 20 females, aged 42-75 years. All patients underwent susceptibility-weighted imaging (SWI) scanning, then SWI data was post-processed to obtain QSM. The semi-automatic dynamic programming algorithm was used to get the volume and mean susceptibility value of each CMB by sketching the boundary of CMBs. The CMBs iron load total volume were calculated. Stepwise linear regression analysis was used to explore independent influencing factors for the number, total volume, and total iron burden of CMBs in ESRD patients. Partial correlation analysis was used to explore the relationship between CMBs and cognitive impairment with the other signs of cerebral small vessel diseases as covariates.Results:In patients with ESRD, CMBs were located in the frontal lobe in 19 cases, parietal lobe in 9 cases, temporal lobe in 19 cases, occipital lobe in 14 cases, basal ganglia in 27 cases, dorsal thalamus in 15 cases, centrum semiovale in 14 cases, cerebellum in 14 cases, and brainstem in 13 cases. C-reactive protein levels (95% CI 101.81-157.85, r=0.96, P=0.001) and creatinine levels (95% CI 5.32-29.61, r=0.71, P=0.010) were influencing factors for the total iron burden of CMBs. C-reactive protein levels (95% CI 0.72-1.15, r=0.99, P=0.001) and creatinine levels (95% CI 0.03-0.22, r=0.89, P=0.014) were influencing factors for the total volume of CMBs. C-reactive protein levels (95% CI 0.10-0.12, r=0.96, P=0.001) and alkaline phosphatase levels (95% CI 0.16-0.38, r=0.59, P=0.001) were influencing factors for the number of CMBs. The total volume ( r=-0.61, P=0.009) and total iron burden ( r=-0.71, P=0.002) of CMBs in the frontal lobe were negatively correlated with cognitive function. However, although the number of CMBs in the frontal lobe was negatively correlated with cognitive function, the statistics analysis was insignificant ( r=-0.53, P=0.063). Conclusions:C-reactive protein and creatinine are influencing factors for CMBs′ total volume and total iron burden; C-reactive protein levels and alkaline phosphatase are influencing factors for the number of CMBs. The total iron burden and total volume of CMBs in the frontal lobe may be the biomarkers of cognitive impairment in patients with end-stage renal disease.