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1.
Asian Journal of Andrology ; (6): 217-222, 2023.
Article in English | WPRIM | ID: wpr-971029

ABSTRACT

The Prostate Imaging Reporting and Data System (PI-RADS) has good ability to identify the nature of lesions on prostate magnetic resonance imaging (MRI). However, some lesions are still reported as PI-RADS 4 and 5 but are biopsy-proven benign. Herein, we aimed to summarize the reasons for the negative prostate biopsy of patients who were assessed as PI-RADS 4 and 5 by biparameter MRI. We retrospectively sorted out the prostate MRI, treatment, and follow-up results of patients who underwent a biparameter MRI examination of the prostate in The First Affiliated Hospital of Nanjing Medical University (Nanjing, China) from August 2019 to June 2021 with PI-RADS 4 and 5 but a negative biopsy. We focused on reviewing the MRI characteristics. A total of 467 patients underwent transperineal prostate biopsy. Among them, biopsy pathology of 93 cases were negative. After follow-up, 90 patients were ruled out of prostate cancer. Among the 90 cases, 40 were considered to be overestimated PI-RADS after review. A total of 22 cases were transition zone (TZ) lesions with regular appearance and clear boundaries, and 3 cases were symmetrical lesions. Among 15 cases, the TZ nodules penetrated the peripheral zone (PZ) and were mistaken for the origin of PZ. A total of 17 cases of lesions were difficult to distinguish from prostate cancer. Among them, 5 cases were granulomatous inflammation (1 case of prostate tuberculosis). A total of 33 cases were ambiguous lesions, whose performance was between PI-RADS 3 and 4. In summary, the reasons for "false-positive MRI diagnosis" included PI-RADS overestimation, ambiguous images giving higher PI-RADS, diseases that were really difficult to distinguish, and missed lesion in the initial biopsy; and the first two accounted for the most.


Subject(s)
Male , Humans , Prostatic Neoplasms/pathology , Magnetic Resonance Imaging/methods , Retrospective Studies , Image-Guided Biopsy/methods , Prostate/pathology
2.
Asian Journal of Andrology ; (6): 287-295, 2023.
Article in English | WPRIM | ID: wpr-981942

ABSTRACT

Most prostate cancers initially respond to androgen deprivation therapy (ADT). With the long-term application of ADT, localized prostate cancer will progress to castration-resistant prostate cancer (CRPC), metastatic CRPC (mCRPC), and neuroendocrine prostate cancer (NEPC), and the transcriptional network shifted. Forkhead box protein A1 (FOXA1) may play a key role in this process through multiple mechanisms. To better understand the role of FOXA1 in prostate cancer, we review the interplay among FOXA1-targeted genes, modulators of FOXA1, and FOXA1 with a particular emphasis on androgen receptor (AR) function. Furthermore, we discuss the distinct role of FOXA1 mutations in prostate cancer and clinical significance of FOXA1. We summarize possible regulation pathways of FOXA1 in different stages of prostate cancer. We focus on links between FOXA1 and AR, which may play different roles in various types of prostate cancer. Finally, we discuss FOXA1 mutation and its clinical significance in prostate cancer. FOXA1 regulates the development of prostate cancer through various pathways, and it could be a biomarker for mCRPC and NEPC. Future efforts need to focus on mechanisms underlying mutation of FOXA1 in advanced prostate cancer. We believe that FOXA1 would be a prognostic marker and therapeutic target in prostate cancer.


Subject(s)
Humans , Male , Androgen Antagonists/therapeutic use , Androgens/metabolism , Hepatocyte Nuclear Factor 3-alpha/metabolism , Mutation , Prostatic Neoplasms, Castration-Resistant/drug therapy , Receptors, Androgen/metabolism
3.
Asian Journal of Andrology ; (6): 687-694, 2023.
Article in English | WPRIM | ID: wpr-1009793

ABSTRACT

Recent studies revealed the relationship among homologous recombination repair (HRR), androgen receptor (AR), and poly(adenosine diphosphate-ribose) polymerase (PARP); however, the synergy between anti-androgen enzalutamide (ENZ) and PARP inhibitor olaparib (OLA) remains unclear. Here, we showed that the synergistic effect of ENZ and OLA significantly reduced proliferation and induced apoptosis in AR-positive prostate cancer cell lines. Next-generation sequencing followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed the significant effects of ENZ plus OLA on nonhomologous end joining (NHEJ) and apoptosis pathways. ENZ combined with OLA synergistically inhibited the NHEJ pathway by repressing DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and X-ray repair cross complementing 4 (XRCC4). Moreover, our data showed that ENZ could enhance the response of prostate cancer cells to the combination therapy by reversing the anti-apoptotic effect of OLA through the downregulation of anti-apoptotic gene insulin-like growth factor 1 receptor ( IGF1R ) and the upregulation of pro-apoptotic gene death-associated protein kinase 1 ( DAPK1 ). Collectively, our results suggested that ENZ combined with OLA can promote prostate cancer cell apoptosis by multiple pathways other than inducing HRR defects, providing evidence for the combined use of ENZ and OLA in prostate cancer regardless of HRR gene mutation status.


Subject(s)
Male , Humans , Prostatic Neoplasms, Castration-Resistant/genetics , Drug Resistance, Neoplasm/genetics , Cell Line, Tumor , Receptors, Androgen/genetics , Nitriles , Apoptosis
4.
Journal of Peking University(Health Sciences) ; (6): 394-399, 2022.
Article in Chinese | WPRIM | ID: wpr-940980

ABSTRACT

OBJECTIVE@#To explore whether WNT signaling pathway genes were associated with non-syndromic oral clefts (NSOC) based on haplotypes analyses among 1 008 Chinese NSOC case-parent trios.@*METHODS@#The genome-wide association study (GWAS) data of 806 Chinese non-syndromic cleft lip with or without cleft palate (NSCL/P) trios and 202 Chinese non-syndromic cleft palate (NSCP) case-parent trios were drawn from the International Consortium to Identify Genes and Interactions Controlling Oral Clefts (ICOCs) study GWAS data set, whose Chinese study population were recruited from four provinces in China, namely Taiwan, Shandong, Hubei, and Sichuan provinces. The process of DNA genotyping was conducted by the Center for Inherited Disease Research in the Johns Hopkins University, using Illumina Human610-Quad v.1_B Bead Chip. The method of sliding windows was used to determine the haplotypes for analyses, including 2 SNPs haplotypes and 3 SNPs haplotypes. Haplotypes with a frequency lower than 1% were excluded for further analyses. To further assess the association between haplotypes and NSOC risks, and the transmission disequilibrium test (TDT) was performed. The Bonferroni method was adopted to correct multiple tests in the study, with which the threshold of statistical significance level was set as P < 0.05 divided by the number of tests, e.g P < 3.47×10-4 in the current stu-dy. All the statistical analyses were performed by using plink (v1.07).@*RESULTS@#After quality control, a total of 144 single nucleotide polymorphisms (SNPs) mapped in seven genes in WNT signaling pathway were included for the analyses among the 806 Chinese NSCL/P trios and 202 Chinese NSCP trios. A total of 1 042 haplotypes with frequency higher than 1% were included for NSCL/P analyses and another 1 057 haplotypes with frequency higher than 1% were included for NSCP analyses. Results from the TDT analyses showed that a total of 69 haplotypes were nominally associated with the NSCL/P risk among Chinese (P < 0.05). Another 34 haplotypes showed nominal significant association with the NSCP risk among Chinese (P < 0.05). However, none of these haplotypes reached pre-defined statistical significance level after Bonferroni correction (P>3.47×10-4).@*CONCLUSION@#This study failed to observe any statistically significant associations between haplotypes of seven WNT signaling pathway genes and the risk of NSOC among Chinese. Further studies are warranted to replicate the findings here.


Subject(s)
Humans , Cleft Lip/genetics , Cleft Palate/genetics , Genetic Predisposition to Disease , Genome-Wide Association Study , Genotype , Haplotypes , Polymorphism, Single Nucleotide , Wnt Signaling Pathway/genetics
5.
Chinese Journal of Thoracic and Cardiovascular Surgery ; (12): 404-409, 2021.
Article in Chinese | WPRIM | ID: wpr-912295

ABSTRACT

Objective:To analyse the effect of preoperative renal function classification on early outcomes for patients with acute type A aortic dissection(AAAD) and to estimate the risk factors of postoperative major adverse events.Methods:From January 2012 to December 2019, 226 patients with AAAD who underwent total arch replacement at our institution were retrospectively analysed, including 146 males and 80 females, aged(54.4±12.5) years old. Stages of preoperative renal function were defined as follows: Normal[estimated glomerular ltration rate(eGFR)≥90 ml·min -1·1.73 m -2, 68 cases], Mild(eGFR 60-89 ml·min -1·1.73 m -2, 73 cases); Moderate(eGFR 30-59 ml·min -1·1.73 m -2, 57 cases), Severe(eGFR<30 ml·min -1·1.73 m -2, 28 cases). The independent risk factors for postoperative death were analyzed by logistic regression analysis. The area under the receiver operating characteristic curve was used to assess the efficiency of eGFR for predicting the postoperative hemodialysis. Results:In-hospital death occurred in 24(10.6%) cases. Major complications included postoperative hemodialysis in 49(21.7%) cases, stroke in 19(8.4%) cases and tracheotomy in 15(6.6%) cases. The best cut-off value of the eGFR for predicting postoperative hemodialysis was 36.5 ml·min -1·1.73 m -2(area under the receiver operating characteristic curve was 0.793). The following variables were found to be risk factors of in-hospital mortality in multivariate logistic regression analysis: serum creatinine, eGFR<30 ml·min -1·1.73 m -2, neural malperfusion, bowel malperfusion, postoperative stroke and hemodialysis. Conclusion:Total arch replacement can be safely performed in patients with AAAD and mild renal dysfunction. Preoperative renal dysfunction is a risk factor for postoperative hemodialysis, and eGFR is useful for predicting the requirement for hemodialysis after total arch replacement. The severity of preoperative renal dysfunction could greatly influence the outcomes after total arch replacement for AAAD. More importance should be attached to the assessment of preoperative renal function during clinical risk assessment.

6.
Journal of Peking University(Health Sciences) ; (6): 815-820, 2020.
Article in Chinese | WPRIM | ID: wpr-942080

ABSTRACT

OBJECTIVE@#In this study, we used genome-wide association study (GWAS) data to explore whether WNT pathway genes were associated with non-syndromic oral clefts (NSOC) considering gene-gene interaction and gene-environment interaction.@*METHODS@#We conducted the analysis using 806 non-syndromic cleft lip with or without cleft palate (NSCL/P) case-parent trios and 202 non-syndromic cleft palate (NSCP) case-parent trios among Chinese populations selected from an international consortium established for a GWAS of non-syndromic oral clefts. Genotype data and maternal environmental exposures were collected through DNA samples and questionnaires. Conditional Logistic regression models were adopted to explore gene-gene interaction and gene-environment in teraction using trio package in R software. The threshold of significance level was set as 3.47×10-4 using Bonferroni correction.@*RESULTS@#A total of 144 single nucleotide polymorphisms (SNPs) in seven genes passed the quality control process in NSCL/P trios and NSCP trios, respectively. Totally six pairs of SNPs interactions showed statistically significant SNP-SNP interaction (P < 3.47×10-4) after Bonferroni correction, which were rs7618735 (WNT5A) and rs10848543 (WNT5B), rs631948 (WNT11) and rs556874 (WNT5A), and rs631948 (WNT11) and rs472631 (WNT5A) among NSCL/P trios; rs589149 (WNT11) and rs4765834 (WNT5B), rs1402704 (WNT11) and rs358792 (WNT5A), and rs1402704 (WNT11) and rs358793 (WNT5A) among NSCP trios, respectively. In addition, no significant result was found for gene-environment interaction analysis in both of the NSCL/P trios and NSCP trios.@*CONCLUSION@#Though this study failed to detect significant association based on gene-environment interactions of seven WNT pathway genes and the risk of NSOC, WNT pathway genes may influence the risk of NSOC through potential gene-gene interaction.


Subject(s)
Humans , Asian People/genetics , Cleft Lip/genetics , Cleft Palate/genetics , Genome-Wide Association Study , Wnt Signaling Pathway/genetics
7.
Journal of Peking University(Health Sciences) ; (6): 809-814, 2020.
Article in Chinese | WPRIM | ID: wpr-942079

ABSTRACT

OBJECTIVE@#Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect, affecting 1.4 per 1 000 live births, and multiple genetic and environmental risk factors influencing its risk. All the known genetic risk factors accounted for a small proportion of the heritability. Several authors have suggested parent-of-origin effects (PoO) may play an important role in the etiology of this complex and heterogeneous malformation. To clarify the genetic association between PTCH1, PTCH2, SHH and SMO in hedgehog (HH) pathway and NSCL/P, as well as testing for potential PoO effects in Chinese case-parent trios.@*METHODS@#We tested for transmission disequilibrium tests (TDT) and PoO effects using 83 common single nucleotide polymorphic (SNP) markers of HH pathway genes from 806 NSCL/P case-parent trios. These trios were drawn from an international consortium established for a genome-wide association studies (GWAS) of non-syndromic oral clefts of multiple ethnicities. DNA samples were collected from each trio. Single marker and haplotype based analysis were performed both in TDT tests and PoO effects. SNPs were excluded if they (ⅰ) had a call rate of < 95%, (ⅱ) had a minor allele frequency (MAF) of < 0.05, (ⅲ) had Mendelian errors over all trios of >5%, (ⅳ) had a genotype distribution in the parents that deviated from the Hardy-Weinberg equilibrium (HWE) (<i>P</i> < 0.000 1). The process was done using Plink (version 1.07, <a href="http://pngu.mgh.harvard.edu/~purcell/plink/data.shtml" target="_blank">http://pngu.mgh.harvard.edu/~purcell/plink/data.shtml</a>). TDT test was performed in Plink v1.07. A log-linear model was used to explore PoO effects using Haplin v6.2.1 as implemented in R package v3.4.2. Significance level was assessed using the Bonferroni correction.@*RESULTS@#A total of 18 SNPs were dropped due to low MAF, thus leaving 65 SNPs available for the analysis. Thus the Bonferroni threshold was 7.7×10-4 (0.05/65). Nominal significant association with NSCL/P was found at a SNP (rs4448343 in PTCH1, P=0.023) and six haplotypes (rs10512249-rs4448343, rs1461208-rs7786445, rs10512249-rs4448343, rs16909865-rs10512249-rs4448343, rs1461208-rs7786445-rs12698335, and rs288756-rs288758-rs1151790, P < 0.05). A total of six haplotypes (rs288765-rs1233563, rs12537550-rs11765352, rs872723-rs288765-rs1233563, rs288765-rs1233563-rs288756, rs6459952-rs12537550-rs11765352, and rs12537550-rs11765352-rs6971211) showed PoO effect (P < 0.05). None of the results remained significant after the Bonferroni correction (P>7.7×10-4).@*CONCLUSION@#Neither significant association between SNPs within HH pathway and the risk of NSCL/P nor PoO effects was seen in this study.


Subject(s)
Humans , Asian People , Cleft Lip/genetics , Cleft Palate/genetics , Genome-Wide Association Study , Hedgehog Proteins/genetics , Patched-2 Receptor , Smoothened Receptor
8.
Journal of Sun Yat-sen University(Medical Sciences) ; (6): 211-218, 2019.
Article in Chinese | WPRIM | ID: wpr-817733

ABSTRACT

@#【Objective】 To investigate the relationship between the expression of PRDX3 (thioredoxin-dependent peroxide reductase)and the occurrence and development of ccRCC (clear cell renal cell carcinoma). 【Methods】 The expression of PRDX3 was first verified in 16 cases of ccRCC tissues and adjacent normal tissues. In the present study , according to the PRDX3 over-expression level,we established the stable PRDX3 overexpression cell lines and knockdown cell lines in 786-O cell lines. We detected the growth rate of tumor cells after overexpression and knockdown of PRDX3. Interaction proteins with PRDX3 were searched by anti-flag pull-down test combined with LC- MS/MS technique. The interaction between PRDX3 and PRDX1(peroxiredoxin 1)was preliminarily explored.【Results】The western blot results showed that PRDX3 were down- regulated in 14 out of 16 ccRCC tissue samples about 1.78 times. Stable PRDX3 overexpression and knockdown cell lines and those control group were successfully established[786O- PRDX3(+)and 786O- PRDX3(-),786O- PRDX3 KN and 786O- PRDX3 NCi]. PRDX3 expression in 786O- PRDX3(+)was 2.1 times higher than 786O- PRDX3(-)at mRNA level and 1.8 times at protein level. PRDX3 expression in 786O- PRDX3 KN was 0.48 times lower than 786O-PRDX3 NCi at mRNA level and 0.51 times at protein level. The cell growth rate of 786O-PRDX3 (+)cell lines was significantly lower than that of 786O-PRDX3(-). Meanwhile ,there was no significant difference in 786O-PRDX3 KN and NCi cell lines. Pull-down results shows that PRDX3 may interact with PRDX1 through disulfide bond and the binding sites of those two proteins were identified respectively.【Conclusion】PRDX3 was down- regulated expression in renal clear cell carcinoma and the interaction with PRDX1 may be involved in the occurrence and development of tumor. Increasing the expression level of PRDX3 can significantly reduce the growth rate of tumor cells. Based on PRDX3 ,it is possible to develop targeted drugs for treating renal clear cell carcinoma.

9.
Chinese Journal of Epidemiology ; (12): 670-675, 2019.
Article in Chinese | WPRIM | ID: wpr-805451

ABSTRACT

Objective@#Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect with its genetic evidence widely explored. This study explored the potential the parent-of-origin (PoO) effect of WNT pathway on the risks of NSCL/P, using a case-parent trio design.@*Methods@#Data on the single nucleotide polymorphism (SNP) of WNT genes were selected from a genome-wide association study (GWAS). A total of 806 Chinese non-syndromic cleft lip patients, with or without cleft palate (NSCL/P) case-parent trios, were gathered from an international consortium. PoO effect of WNT pathway genes and its haplotypes were explored by log-linear models. Additional Wald tests were performed to assess: a) the heterogeneity of PoO effect between different maternal exposures, b) the interaction between PoO effect, c) maternal exposure to environmental tobacco smoke (ETS), and d) multivitamin supplementation during pregnancy. The threshold for statistical significance was adjusted as 3.47×10-4, according to Bonferroni correction.@*Results@#After quality control, a total of 144 SNPs within seven genes were included for analyses, among which 8 SNPs were of potential PoO effect (P<0.05). However, none of them achieved the statistical significance after Bonferroni correction. The haplotype rs4074668-rs12725747 (T-A) on WNT9A showed significant PoO effect, based on the haplotype test for PoO (P=2.74×10-4). In addition, no statistically significant interaction was found in further exploration of this haplotype under environmental exposures as ETS or multivitamin supplementation.@*Conclusions@#Genes in the WNT pathway may influence the NSCL/P risks through the potential PoO effect. Particularly, the haplotype rs4074668-rs12725747 (T-A) on WNT9A presented significant PoO effect on NSCL/P, statistically. From this current study, findings on WNT pathway related risks among the NSCL/P, need to be further validated by independent samples in the future.

10.
Journal of Peking University(Health Sciences) ; (6): 564-570, 2019.
Article in Chinese | WPRIM | ID: wpr-941850

ABSTRACT

OBJECTIVE@#To explore the association between SPRY gene family and the risk of non-syndromic oral clefts among Chinese populations, in respect of single nucleotide polymorphisms (SNPs) association and parent-of-origin effects.@*METHODS@#Based on case-parent design, this study used the data of SPRY gene family in a next generation sequencing study of 183 non-syndromic cleft lip with or without cleft palate (NSCL/P) case-parent trios (549 participants) recruited from 2016 to 2018, to analyze the effects of SNP association and parent-of-origin. The sequencing study adopted a two-stage design. In the first stage, whole exome sequencing was conducted among 24 NSCL/P trios with family history to explore potential signals. Then in the second stage, another 159 NSCL/P trios were used as validation samples to verify the signals found in the first stage. The data of general information, disease features and parental environmental exposures for participants were collected through questionnaires. Blood samples were collected from each participant for DNA extraction and sequencing. Transmission disequilibrium tests (TDT) were conducted to test for the association between SNPs and NSCL/P, while Z score tests were applied to analyze parent-of-origin effects. The analyses were performed using Plink (v1.07). TRIO package in R (v3.5.1). Besides, famSKAT analyses were conducted in the first stage to combine the effect of SNPs located on the same gene, using famSKAT package in R(V3.5.1). Bonferroni method was adopted to correct multiple tests in the second stage.@*RESULTS@#Twenty-two SNPs in SPRY gene family were included for analyses after the quality control process in the first stage. Based on the variants annotation, functional prediction and statistical analysis, rs1298215244 (SPRY1) and rs504122 (SPRY2) were included in the second verification stage. TDTs in the verification stage revealed that rs1298215244: T>C, rs504122: G>C and rs504122: G>T were associated with the risk of NSCL/P after Bonferroni corrections, where rs504122: G>T was a rare variation. Although the test for parent-of-origin effect of rs1298215244: T>C reached nominal significance level, no SNP showed significant association with NSCL/P through parent-of-origin effect after Bonferroni corrections.@*CONCLUSION@#This study found that SNPs (including both common and rare variants) among the SPRY gene family were associated with the risk of NSCL/P among Chinese populations. This study failed to detect parent-of-origin effects among the SPRY gene family.


Subject(s)
Humans , Cleft Lip , Cleft Palate , Genome-Wide Association Study , Genotype , High-Throughput Nucleotide Sequencing , Intracellular Signaling Peptides and Proteins , Membrane Proteins , Polymorphism, Single Nucleotide , Risk Factors
11.
Journal of Experimental Hematology ; (6): 1626-1631, 2018.
Article in Chinese | WPRIM | ID: wpr-773045

ABSTRACT

OBJECTIVE@#To study the promoting-apoptosis effect of HDAC6 on the human leukemia cells and its mechanism.@*METHODS@#The siRNA interference technology was used to inhibit the expression of HDAC6 gene, the RT-PCR and Western blot were used to detect the expression of HDAC6 and related signal pathway proteins respectively, the flow cytometry and Hoechest staining were used to detect the apoptosis and morphology changes of K562 cells.@*RESULTS@#Compared with the periphal blood monocyte and bone marrow stromal cells of healthy volunteers, the expression level of HDAC6 in leukemia cell lines was up-regulated significantly(P<0.05); the flow cytometry and Hoechest staining showed that after interference of HDAC6 gene, the apoptosis of K562 cells increased, moreover the cell morphology was changed; the Western blot detection showed that the interfering HDAC6 increased BAX/BCL-2 ratio and cleaved caspase 3 expression, and activated the MAPK, ATK, ERK signaling pathway.@*CONCLUSION@#The interferance of HDAC6 can promote the K562 cell apoptosis, its mechanism may relate with activation of MAPK signaling pathway.


Subject(s)
Humans , Apoptosis , Cell Proliferation , Down-Regulation , Histone Deacetylase 6 , K562 Cells , Leukemia , RNA, Small Interfering
12.
International Eye Science ; (12): 1440-1442, 2018.
Article in Chinese | WPRIM | ID: wpr-731253

ABSTRACT

@#AIM:To investigate the correlation of serum miR-146a with nuclear factor-κB(NF-κB)and vascular endothelial growth factor(VEGF)in diabetic retinopathy patients. <p>METHODS: A total of 100 patients with T2DM treated in our hospital from July 2016 to December 2017 were assigned into T2DM patients with DR(DR group, <i>n</i>=32)and T2DM patients without DR(T2DM group, <i>n</i>=68). Thirty healthy volunteers were selected as control group. Real-time PCR was used to examine the expression of miR-146a. Enzyme linked immunosorbent assay was used to detect the levels of NF-κB and VEGF. The correlation between miR-146a and NF-κB and VEGF was analyzed. <p>RESULTS: Compared with the control group, HbA1c in T2DM group and DR group increased(<i>t</i>=6.822, 5.709; <i>P</i><0.001), FBG increased(<i>t</i>=8.889, 7.923; <i>P</i><0.001), 2hPBG increased(<i>t</i>=6.646, 5.514; <i>P</i><0.001). Compared with T2DM group, the duration of diabetes in DR group was longer(<i>t</i>=2.431, <i>P</i>=0.017). Compared with the control group, serum miR-146a in T2DM and group DR significantly decreased(<i>t</i>=3.967, 7.169; <i>P</i><0.001), and the DR group was lower than that in the T2DM group(<i>t</i>=4.444, <i>P</i><0.001). Compared with the control group, the serum NF-κB in the T2DM and DR group increased significantly(<i>t</i>=6.063, 14.851; <i>P</i><0.001), VEGF increased significantly(<i>t</i>=7.613, 12.943; <i>P</i><0.001), NF-κB and VEGF in DR group were larger than those in T2DM group(<i>t</i>=11.406, 7.560; <i>P</i><0.001). Pearson analysis showed that miR-146a was negatively correlated with NF-κB and VEGF(<i>r</i>=-0.503, -0.574; <i>P</i><0.05). <p>CONCLUSION: The serum miR-146a in DR patients significantly decreased, the NF-κB and VEGF significantly increased. MiR-146a may be involved in the pathogenesis of DR by mediating inflammatory reaction and vascular proliferation.

13.
Chinese Journal of Epidemiology ; (12): 1402-1407, 2018.
Article in Chinese | WPRIM | ID: wpr-738159

ABSTRACT

Objective To describe the study design,the characteristics of participants as well as the pedigrees included in the baseline survey of Fujian Tulou Family Cohort Study.Methods Fujian Tulou Family Cohort Study was a prospective open cohort study with a biological sample bank.A baseline survey was conducted in Tulou areas of Nanjing county in Fujian province from 2015 to 2018,including questionnaire survey,physical and biochemical indicators examinations,and blood sample collection in adults aged ≥ 18 years.In addition,family relationship of the participants was also recorded.The pedigree information of the juveniles under 18 years old were also collected.Results The baseline survey included 2 727 individuals in two clans,of whom 2 373 (87.0%) were adults,and 2 126 participants completed questionnaires,physical examinations and biochemical tests.The average age of the 2 126 participants was (57.9 ± 13.3) years,with 39.4% being males.The current smoking rates in male and female participants were 41.2% and 2.1%,respectively.The corresponding rates of current alcohol consumption were 19.0% and 2.6%.For common chronic diseases,the prevalence rates were 51.3% for hypertension,9.7% for diabetes and 26.7% for hyperlipemia according to the self-reported disease diagnoses,health examination results and biochemical examination results in class 1Ⅱor Ⅲ hospitals.Based on the family relationship information and genealogical data,710 pedigrees were finally identified,consisting of 5 087 family members.The numbers of five,four,three,and two generations pedigrees were 3,88,238 and 381,respectively.The pairs of the first to the fifth degree relatives were 12 039,2 662,1 511,202 and 31,respectively.Conclusion The establishment of Fujian Tulou Family Cohort provides valuable resources for exploring the genetic risk factors,environmental risk factors and gene-environment interactions contributing to the risk of common chronic diseases.

14.
Chinese Journal of Epidemiology ; (12): 387-390, 2018.
Article in Chinese | WPRIM | ID: wpr-737967

ABSTRACT

Non-syndromic oral clefts (NSOC) are among the most common birth defects.The prevalence of NSOC is 1.13-1.30 per 1 000 live births in China,which is higher than those in other major ethnic groups.The etiology of NSOC is complex and heterogeneous,which involves both genetic and environmental risk factors.Although genome-wide association studies have identified a number of risk loci,these loci can only account for a small proportion of the heritability of NSOC.The next-generation sequencing research provides new ideas for further exploring the genetic risk factors of NSOC.This paper summaries the progress in the next-generation sequencing research of NSOC.

15.
Chinese Journal of Epidemiology ; (12): 1402-1407, 2018.
Article in Chinese | WPRIM | ID: wpr-736691

ABSTRACT

Objective To describe the study design,the characteristics of participants as well as the pedigrees included in the baseline survey of Fujian Tulou Family Cohort Study.Methods Fujian Tulou Family Cohort Study was a prospective open cohort study with a biological sample bank.A baseline survey was conducted in Tulou areas of Nanjing county in Fujian province from 2015 to 2018,including questionnaire survey,physical and biochemical indicators examinations,and blood sample collection in adults aged ≥ 18 years.In addition,family relationship of the participants was also recorded.The pedigree information of the juveniles under 18 years old were also collected.Results The baseline survey included 2 727 individuals in two clans,of whom 2 373 (87.0%) were adults,and 2 126 participants completed questionnaires,physical examinations and biochemical tests.The average age of the 2 126 participants was (57.9 ± 13.3) years,with 39.4% being males.The current smoking rates in male and female participants were 41.2% and 2.1%,respectively.The corresponding rates of current alcohol consumption were 19.0% and 2.6%.For common chronic diseases,the prevalence rates were 51.3% for hypertension,9.7% for diabetes and 26.7% for hyperlipemia according to the self-reported disease diagnoses,health examination results and biochemical examination results in class 1Ⅱor Ⅲ hospitals.Based on the family relationship information and genealogical data,710 pedigrees were finally identified,consisting of 5 087 family members.The numbers of five,four,three,and two generations pedigrees were 3,88,238 and 381,respectively.The pairs of the first to the fifth degree relatives were 12 039,2 662,1 511,202 and 31,respectively.Conclusion The establishment of Fujian Tulou Family Cohort provides valuable resources for exploring the genetic risk factors,environmental risk factors and gene-environment interactions contributing to the risk of common chronic diseases.

16.
Chinese Journal of Epidemiology ; (12): 387-390, 2018.
Article in Chinese | WPRIM | ID: wpr-736499

ABSTRACT

Non-syndromic oral clefts (NSOC) are among the most common birth defects.The prevalence of NSOC is 1.13-1.30 per 1 000 live births in China,which is higher than those in other major ethnic groups.The etiology of NSOC is complex and heterogeneous,which involves both genetic and environmental risk factors.Although genome-wide association studies have identified a number of risk loci,these loci can only account for a small proportion of the heritability of NSOC.The next-generation sequencing research provides new ideas for further exploring the genetic risk factors of NSOC.This paper summaries the progress in the next-generation sequencing research of NSOC.

17.
Journal of Sun Yat-sen University(Medical Sciences) ; (6): 34-40, 2018.
Article in Chinese | WPRIM | ID: wpr-712910

ABSTRACT

[Objective]To investigate the effect of KIF23 gene expression on the proliferation,migration and invasion of human hepatocellular carcinoma HepG2 cells in vitro,and to explore the possible mechanism.[Methods]The KIF23 siRNA was transfected into HepG2 cells by lipofectamine 3000.The expression of KIF23 mRNA and protein in HepG2 cells was de-tected by qRT-PCR and Western blot.The effect of silencing KIF23 on the proliferation of HepG2 cells was studied by CCK-8 assay and plate clone formation assay.The tumor cell abilities of migration and invasion after transfection were measured by scratch assay and Transwell assay.The expression of protein kinase B(PKB/Akt)and phosphorylated Akt(p-Akt)protein in HepG2 cells transfected with KIF23-siRNA2 was detected by Western blot.[Results]KIF23-siRNA could effectively si-lence the expression of KIF23 mRNA and protein in HepG2 cells(P<0.01).The results of CCK-8 assay,plate clone forma-tion assay,scratch assay and Transwell assay demonstrated that the cell proliferation,migration and invasion ability of the KIF23-siRNA2 interference group were significantly inhibited,compared to the negative control group and the blank control group(P<0.05).The expression level of total Akt protein in HepG2 cells was not changed,but the expression level of phos-phorylated Akt protein was down-regulated(P<0.05).[Conclusions]KIF23 may promote the proliferation,migration and in-vasion of human hepatocellular carcinoma cells by activating Akt signal transduction pathway.KIF23 is expected to be a new target for gene therapy of hepatocellular carcinoma.

18.
Chinese Journal of Medical Science Research Management ; (4): 387-390, 2018.
Article in Chinese | WPRIM | ID: wpr-712316

ABSTRACT

Objective To enhance the recognition of the ethical principles and provide reference for the ethical review in medical research involving human subjects.Methods By summarizing the ethical review of the projects involving human subjects in past three years,analyzing common issues identified,and proposing the corresponding solutions.Results Conducting ethical review for research involving human subject according to ethical principles,is helpful for the protection of human subject,and also for the internationalization of medical research in China.Conclusions For the development of medical research in long term,the ethical review is necessary.All investigators need to improve their understandings and execute the ethical principles well in their research practice.

19.
Chinese Journal of Immunology ; (12): 1326-1330,1335, 2017.
Article in Chinese | WPRIM | ID: wpr-615171

ABSTRACT

Objective:To observe the effect of low-expression or over-expression of NUP88 gene on the proliferation and invasion ability of breast cancer cell line BT-20.Methods: NUP88 recombinant adenovirus expression vector and NUP88 RNAi adenovirus vector were transfected into breast cancer BT-20 cells to obtain BT-20 cells over-expressing NUP88 and BT-20 cells lower-expressing NUP88 and then detected the expression of NUP88 mRNA and NUP88 protein.After that,the apoptosis of BT-20 cells was detected by flow cytometry and the invasion and metastasis of BT-20 cells were detected by Transwell invasion assay.The expression of apoptosis protein and invasion and metastasis proteins were detected by Western blot.Results: BT-20 cell with the over expression levels of NUP88 mRNA and NUP88 protein and BT-20 cell with the low expression levels of NUP88 mRNA and NUP88 protein were structured.The over-expression of NUP88 gene led to proliferation rate and the number of invasive cells were significantly higher than BT-20 cells,apoptosis cells were significantly lower than BT-20 cells(P<0.05).However,the low-expression of NUP88 gene led to proliferation rate and the number of invasive cells were significantly lower than BT-20 cells,apoptosis cells was significantly higher than BT-20 cells(P<0.05).The over-expression of NUP88 gene led to Bcl-2 and β-catenin level were significantly higher than that of BT-20 cells,and Bax and E-cadherin level were significantly lower than that of BT-20 cells(P<0.05).However,the low-expression of NUP88 gene led to Bcl-2 and β-catenin level were significantly lower than that of BT-20 cells,and Bax and E-cadherin level were significantly higher than that of BT-20 cells(P<0.05).Conclusion: NUP88 gene regulates the proliferation and invasion and migration ability of breast cancer cells by regulating the expression of Bax,Bcl-2,E-cadherin and β-catenin.It has an important significance in the target treatment of breast cancer.

20.
Journal of Shanghai Jiaotong University(Medical Science) ; (12): 348-351, 2017.
Article in Chinese | WPRIM | ID: wpr-515260

ABSTRACT

Objective · To evaluate the surgical outcome of RPR composite technique for complex hypertrophic obstructive cardiomyopathy (HOCM). Methods · From June 2009 to December 2015, 9 complex HOCM patients received RPR procedure. There were 6 males and 3 females with age from 22 to 63 years old and the average age of (43±19) years old. Transthorax echocardiography (TTE) showed systolic anterior motion (SAM) and at least moderate mitral valve regurgitation (MR) in all patients before operations. Transesophageal echocardiography (TEE) was used to evaluate the results of procedures during operation. All the patients had been followed up since one week after operation and examined by TTE. Results · All the patients were discharged without complications. Intraoperative TEE indicated that left ventricular outflow tract pressure gradient (LVOTPG) significantly decreased from (92±14) mmHg before operation to (9±3) mmHg after operation (P<0.01). SAM in all the patients disappeared. One week after operation, TTE demonstrated remarkable reduction in the thickness of ventricular septum, LVOTPG and MR than those before operation (P<0.01). Mean follow-up was 26 months. All the patients became asymptomatic. LVOTPG remained low and MR remained mild. There were no deaths, reoperations, or any other adverse consequences. Conclusion · RPR technique is an effective surgical method to relieve LVOTO and MR of complex HOCM to lead a better life.

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