1.The research progress on NAMPT in malignant tumors
Practical Oncology Journal 2016;30(2):158-161
Nicotinamide phosphoribosyltransferase( NAMPT) is the rate-limiting enzyme that catalyzes the first step in Nicotinamide adenine dinucleotide( NAD) biosynthesis and regulates biological processes such as metab-olism,growth and apoptosis of cells.In the past few years,a large number of studies have found that expression level of NAMPT is increased in a variety of malignancies,which is associated with the progression and treatment of malig-nant tumors.The research of the mechanism of NAMPT in malignant tumors and molecule inhibitors of the NAMPT have brought new hope and prospect for the treatment of malignant tumors.This article makes a brief review of NAMPT research status in malignant tumors.
2.Learning from Neijing to Explore the TCM Name and Pathogensis of Hypertension
Guanghao LI ; Lin SHEN ; Duan ZHOU
Journal of Zhejiang Chinese Medical University 2014;(2):134-136
[Objective]Discussion on TCM name and pathogenesis of hypertension. [Method]To further explore and analyze the TCM name, location as wel as pathogenssis of hypertension after learning“Neijing”. [Result]Hypertension corresponding TCM diseases should be the veins bulge from“Neijing”. The location of the disease is heart,while it relates to internal organs. The main pathogenesis is that heart commanding blood abnormality. [Conclusion ]The traditional classical dialectical mode from the liver treatment of hypertension should be changed,the clinical treatment of hypertension is due to the heart according to the theory of pathogenesis which the heart commands blood vessels.Seeking the key reason is important to differential treatment of hypertension.
3.Study of commercial strategies of biomedical engineering scientific Achievements transfer in military universities
Xueqi LI ; Jianqi WANG ; Erping LUO ; Guanghao SHEN ; Jiaxue QI
Chinese Medical Equipment Journal 2004;0(08):-
In this paper,the low rate of commercial of biomedical engineering scientific achievements transfer in military universities was discussed in detail.The main problems were analyzed.The commercial strategies of biomedical engineering scientific achievements transfer inmilitary universities were propound.
4.Analysis of prostatic fluid cytology in patients with elevated PSA
Xin CHEN ; Yuefeng LI ; Ping WANG ; Dongmin YUE ; Qing YE ; Zhuo YANG ; Weiqing ZANG ; Guanghao WANG ; Xiaoguang QU ; Fujin GAO
Chinese Journal of Urology 2012;33(2):123-126
ObjectiveTo study the value of the exfoliative cytology of prostatic fluid obtained from patients with elevated PSA in prostate cancer diagnosis.MethodsProstatic fluid was obtained from 130 patients with elevated PSA before prostate biopsy and then the Wright's stain and cytological class were done.Each cytological class and patient's age,PSA,total prostate volume,prostatic fluid volume and the number of leukocyte in the prostatic fluid were recorded.The relationship of leukocyte number and patient's age,PSA and prostate volume was analyzed by Spearman correlation test.ResultsProstate biopsy pathology results showed that there were 77 (59.2%) cancer cases and 53 (40.8%) non-cancer cases.Patient numbers in cytological class 1 to 5 were 28 (21.5%),32 (24.6%),22 (16.9%),36 (27.7%),12(9.2%),respectively.The prostate fluid cytology had a specificity of 100% and high sensitivity of 62.5%(10/16) in patients with PSA≥20 μg/L.PSA value had significant difference between class 1,2,3,4and 5.Significant correlation was found among the prostatic fluid volume,total leukocyte number and prostate volume.Prostate volume,leukycyte density and total leukycyte number was significant higher in noncancer patients than in prostate cancer patients.ConclusionsThe exfoliative cytology of prostatic fluid is a valuable method in detecting prostate cancer,particularly in patients with high PSA levels.It has the advantages of non-invasion and less injury than prostate biopsy.There is a relationship between elevated PSA value and high leukocyte numbers.
5.The effect of human islet amyloid polypeptide on autophagy in murine INS-1 cells and potential mechanisms
Guanghao XIA ; Yujing JIN ; Jinfeng XIAO ; Xiaotong LI ; Tiehong ZHU
Chinese Journal of Internal Medicine 2018;57(9):667-673
Objective The aims of the study were to investigate the effects of human islet amyloid polypeptide (hIAPP) on autophagy in INS-1 cells and its underlying mechanism,and to explore the role of autophagy in hIAPP-induced cytotoxicity and oxidative stress.Methods INS-1 cells were treated with hIAPP (10 μmol/L) for 24 h in the presence or absence of N-acetyl-L-cysteine (NAC),compound C,5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) and 3-methyladenine (3-MA),respectively.Transmission electron microscopy was used to observe the number of autophagosome in cells.Cell viability was determined by methyl thiazolyl tetrazolium (MTT) test.2',7'-dichlorofluorescin diacetate (DCFH-DA) assay was used to measure the relative levels of reactive oxygen species (ROS).Western blot was used to detect expression of adenosine monophosphate-activated protein kinase (AMPK) and autophagic markers p62 and microtubule associated protein 1 light chain3 (LC3).Results Treatment of INS-1 cells with hIAPP resulted in a significant increase in the number of autophagosomes and the expression of LC3-Ⅱ/LC3-Ⅰ (both P<0.05).Meanwhile,treatment of INS-1 cells with hIAPP enhanced the level of ROS to 1.76 times of control cells (P<0.01).Co-treatment with NAC,an antioxidant,inhibited hIAPP-induced ROS generation,and the expression of LC3-Ⅱ/LC3-Ⅰ and p-AMPK in the INS-1 cells (all P<0.05).Pretreatment of INS-1 cells with AMPK inhibitor compound C suppressed hIAPP and AICAR,an activator of AMPK,induced expression of LC3-Ⅱ/LC3-Ⅰ and p-AMPK (all P<0.05).Autophagic inhibitor 3-MA and compound C aggravated the hIAPP-induced cell death and ROS generation in INS-1 cells (All P<0.05).The cytotoxic effects of hIAPP were significantly attenuated by co-treatment with AICAR (P<0.05).Conclusion Autophagy may act as an adaptive mechanism to alleviate hIAPP-induced oxidative damage and toxicity in INS-1 cells.
6.Therapeutic effect of emergency PCI combined ticagrelor on patients with acute STEMI and its influ— ence on TNF—α level
Wang ZHENG ; Bing DENG ; Lin SHEN ; Nuo TANG ; Guanghao LI ; Yu LIU
Chinese Journal of cardiovascular Rehabilitation Medicine 2019;28(2):177-180
Objective :To explore therapeutic effect of emergency percutaneous coronary intervention (PCI) combined ticagrelor on patients with acute ST elevation myocardial infarction (STEMI ) and its influence on level of tumor necrosis factor (TNF)—α.Methods : A total of 98 patients with acute STEMI treated in our hospital from Jan 2016 to Jan 2017 were selected .Patients were randomly and equally divided into clopidogrel group and ticagrelor group , each group received corresponding medication before PCI .LVEF ,LVEDd ,TNF—α level before and one month after treatment and TIMI grade before and after PCI ,recanalization time ,postoperative corrected TIMI frame (CTFC) , percentages of thrombus aspiration ,auxiliary IABP and no—reflow ,and incidence of adverse events during six—month follow—up after PCI were observed and compared between two groups .Results : Compared with before PCI and treatment ,there were significant rise in LVEF on one month after treatment and TIMI grade after PCI ,and signifi—cant reductions in LVEDd and TNF—α level in two groups on one month after treatment , P=0.001 all.Compared with clopidogrel group on one month after treatment ,there was significant rise in LVEF [ (49.80 ± 4.17 )% vs. (57.32 ± 5.10)%] ,and significant reductions in LVEDd [ (57. 94 ± 4. 70) mm vs .(47.11 ± 3.49) mm] ,TNF—α level [ (17. 82 ± 2.84) pg/ml vs .(8.40 ± 2. 04 ) pg/ml] and postoperative percentage of no—reflow (24.44% vs. 4.44%) in ticagrelor group , P<0. 01 all ,there were no significant difference in other operative related indexes be—tween two groups , P>0.05 all.After six—month follow—up ,incidence rate of composite endpoint events in ticagrelor group was significantly lower than that of clopidogrel group (11. 11% vs.31. 11%) , P=0.021 ,there were no sig—nificant difference in percentages of in—stent thrombus ,infarct related artery revascularization and recurrent unsta—ble angina pectoris between two groups , P>0.05 all .Conclusion : Short—term therapeutic effect of emergency PCI combined ticagrelor is significant .It can significantly improve prognosis ,which is worth extending .
7.Multi-omics Analysis of Primary Cell Culture Models Reveals Genetic and Epigenetic Basis of Intratumoral Phenotypic Diversity
Liu SIXUE ; Yang ZUYU ; Li GUANGHAO ; Li CHUNYAN ; Luo YANTING ; Gong QIANG ; Wu XIN ; Li TAO ; Zhang ZHIQIAN ; Xing BAOCAI ; Xu XIAOLAN ; Lu XUEMEI
Genomics, Proteomics & Bioinformatics 2019;17(6):576-589
Uncovering the functionally essential variations related to tumorigenesis and tumor pro-gression from cancer genomics data is still challenging due to the genetic diversity among patients, and extensive inter-and intra-tumoral heterogeneity at different levels of gene expression regulation, including but not limited to the genomic, epigenomic, and transcriptional levels. To minimize the impact of germline genetic heterogeneities, in this study, we establish multiple primary cultures from the primary and recurrent tumors of a single patient with hepatocellular carcinoma (HCC). Multi-omics sequencing was performed for these cultures that encompass the diversity of tumor cells from the same patient. Variations in the genome sequence, epigenetic modification, and gene expression are used to infer the phylogenetic relationships of these cell cultures. We find the discrepancy among the relationships revealed by single nucleotide variations (SNVs) and transcriptional/epigenomic pro-files from the cell cultures. We fail to find overlap between sample-specific mutated genes and differ-entially expressed genes (DEGs), suggesting that most of the heterogeneous SNVs among tumor stages or lineages of the patient are functionally insignificant. Moreover, copy number alterations (CNAs) and DNA methylation variation within gene bodies, rather than promoters, are significantly correlated with gene expression variability among these cell cultures. Pathway analysis of CNA/DNA methylation-related genes indicates that a single cell clone from the recurrent tumor exhibits distinct cellular characteristics and tumorigenicity, and such an observation is further confirmed by cellular experiments both in vitro and in vivo. Our systematic analysis reveals that CNAs and epigenomic changes, rather than SNVs, are more likely to contribute to the phenotypic diversity among subpop-ulations in the tumor. These findings suggest that new therapeutic strategies targeting gene dosage and epigenetic modification should be considered in personalized cancer medicine. This culture model may be applied to the further identification of plausible determinants of cancer metastasis and relapse.
8.Factors influencing recurrence and survival after resection of intrahepatic cholangiocarcinoma
Peng LI ; Ruizhao QI ; Lingxiang YU ; Hui REN ; Qian CAO ; Guanghao DIAO ; Muyi YANG ; Dexi ZHAO ; Yu ZHANG ; Zhaohai WANG
Chinese Journal of Hepatobiliary Surgery 2022;28(4):270-274
Objective:To analyze the factors influencing prognosis of intrahepatic cholangiocarcinoma (ICC) after surgical resection.Methods:The clinical data of patients diagnosed with ICC and who underwent surgical resection from December 2015 to December 2019 at the Fifth Medical Center of PLA General Hospital were retrospectively analyzed. Of 39 patients who were included in this study, there were 23 males and 16 females, with age of (54.1±7.2) years old. The body mass index, hepatitis B virus infection status, tumor diameter, degree of differentiation, microvascular tumor thrombus, lymph node metastasis, and serum levels of carbohydrate antigen 19-9 (CA19-9) were analyzed as risk factors affecting postoperative recurrence and survival.Results:The median times to recurrence were significantly better in patients with a tumour length <5 cm (11 vs. 5 months), patients without microvascular tumor thrombus (54 vs. 6 months) and patients without lymph node metastasis (8 vs. 5 months) (all P<0.05). The median survival of patients with CA19-9≥100 U/ml was significantly shorter than that of patients with CA19-9<100 U/ml, (9 vs. 27 months, P<0.05). Tumor diameter>5 cm, microvascular tumor thrombus, lymph node metastasis, and CA19-9 ≥100 U/ml are risk factors affecting the recurrence time after ICC resection, CA19-9 ≥100 U/ml is a risk factor affecting survival time after ICC resection. Conclusion:Tumor diameter, microvascular tumor thrombus, lymph node metastasis and CA19-9 can be used to estimate the risk of ICC recurrence, and CA19-9 level can be used to estimate postoperative survival of ICC patients after resection.
9.Construction of prognostic model of head and neck squamous carcinoma with lymph node metastasis-related gene andanalysis of tumor immunity microenvironment
Guanghao ZHU ; Hui YAO ; Haopu LI ; Jingjie WANG ; Minhui ZHU ; Hongliang ZHENG
Chinese Archives of Otolaryngology-Head and Neck Surgery 2024;31(5):287-291
OBJECTIVE To identify the key genes associated with lymph node metastasis in head and neck squamous carcinoma(HNSCC)and construct a prognostic model based on The Cancer Genome Atlas(TCGA)database.METHODS Differentially expressed genes(DEGs)between tumor tissues and normal tissues in the HNSCC dataset in the TCGA database were screened by R software,and gene modules related to lymph node metastasis were screened by weighted gene co-expression network(weighted gene co-expression network analysis,WGCNA).Prognostic risk models were constructed by univariate cox regression and Lasso regression analyses.Survival analyses and ROC curves were performed to verify the Reliability of prognostic models.CIBERSORT,TIMER and ESTIMATE algorithms analysed the differences in the tumor micro environment(TME)of different risk groups.RESULTS There were 2 565 DEGs screened,and a set of gene modules highly correlated with disease prognosis and lymph node metastasis were obtained by WGCNA analysis,and correlation analysis verified that the expression of genes in this gene module was highly correlated with lymph node metastasis.Univariate cox regression and Lasso regression were used to identify 6 key prognostic genes:CDKN2A,CCNE2,KNSTRN,AURKA,KPNA2,and ORC1.A prognostic model was constructed based on the 6 genes,and survival analysis showed that the prognosis of the high-risk group was significantly worse than that of the low-risk group(P<0.0001).The ROC curves demonstrated the good predictive performance of this prognostic model.CIBERSORT analyses revealed differences in the immune microenvironment of tumors in different risk groups.CONCLUSION The 6 key prognostic genes screened were helpful in predicting the prognosis of HNSCC patients and were closely associated with the immune microenvironment of HNSCC,suggesting that they may serve as potential therapeutic targets.
10.MRI features of H3K27M mutant type and wild type astrocyte differentiated diffuse midline glioma in spinal cord
Haikuo WANG ; Jie ZHANG ; Yaowu ZHANG ; Guanghao ZHENG ; Junjie LI ; Yongzhi WANG ; Wenqing JIA
Chinese Journal of Medical Imaging Technology 2024;40(6):815-819
Objective To observe MRI features of H3K27M mutant type and wild type astrocyte differentiated diffuse midline glioma(DMG)in spinal cord.Methods Totally 91 patients with astrocyte differentiation diffuse midline glioma(DMG)in spinal cord confirmed by pathology were retrospectively enrolled and divided into mutant group(n=44)and wild group(n=47)according to H3K27M status.Clinical and MRI manifestations were compared between groups,and logistic regression analysis was used to screen the impact factors of H3K27M mutation.Results The incidence of peritumoral edema and spinal cord cavity in mutant group were lower than those in wild group(both P<0.05),while no significant difference of other parameters was found between groups(all P>0.05).All clinical and MRI parameters were included in logistic regression analysis,and the result showed that they were not influencing factors of H3K27M mutation(all P>0.05).Conclusion The incidence of peritumoral edema and spinal cord cavity in spinal cord H3K27M mutant type astrocyte differentiated DMG were lower than those of wild type,yet not sufficient to be regarded as impact factors for predicting H3K27M mutation of DMG.