Research status of CHEK2 gene and breast cancer / 中国医师杂志

At present, breast cancer is one of the main causes of death for women in the world. In recent years, the incidence rate of breast cancer in China has also been rising. Existing studies have shown that the most fully studied gene for breast cancer susceptibility is breast cancer susceptibility gene 1/2 (BRCA1/2), and other genes related to the increased risk of breast cancer have also been confirmed, including cell-cycle-checkpoint kinase gene 2 (CHEK2), which is a tumor suppressor gene encoding serine/Threonine kinase CHEK2. The gene is involved in DNA repair, cell cycle regulation, apoptosis and other DNA damage response pathways. This article reviews the research status of CHEK2 gene and its important role in the prevention, diagnosis and treatment of breast cancer.

Research progress of p53 protein in the development mechanism of triple negative breast cancer / 中国医师杂志

Tumor suppressor gene p53 plays an important role in regulating cell cycle, controlling apoptosis and repairing damaged DNA. Mutation of this gene is closely related to the occurrence, development and drug resistance of various tumors. The mutant p53 protein is closely related to the growth and metastasis of triple negative breast cancer (TNBC) with higher malignancy and higher risk of metastasis. This paper expounds the mechanism of p53 protein participating in the occurrence, development and metastasis of TNBC, introduces the effect of interfering with mouse dual-microbody gene 2 (MDM2), activated T cell nuclear factor 1 (NFAT1) and other proteins on p53, as well as small molecular targeted drugs closely related to p53 protein, and provides a new direction and theoretical basis for targeted treatment of TNBC.

Comparative analysis of clinicopathological and mammographic findings between ductal carcinoma in situ with microinvasion and ductal carcinoma in situ / 中华放射学杂志

Objective:To comparative analyze mammographic and clinicopathological findings of ductal carcinoma in situ (DCIS) and DCIS with microinvasion (DCISM), and to investigate the predictive factors for DCISM.Methods:A total of 626 patients with DCISM and DCIS confirmed by surgery and pathology in the Affiliated Hospital of Qingdao University from January 2016 to July 2020 were collected and underwent preoperative mammography. The X-ray findings of DCISM and DCIS patients were classified and diagnosed according to the Breast Imaging Reporting and Data System (BI-RADS) criteria. The differences in clinicopathological and radiographic findings between DCISM and DCIS patients were analyzed using χ 2 test or Fisher exact test. The risk factors of DCISM were evaluated by using univariate and multivariate binary logistic regression analysis. Results:Among the 626 cases, 171 were diagnosed as DCISM, 455 were diagnosed as DCIS. Large diameter (≥2.7 cm), high nuclear grade, comedo type, axillary lymph node metastasis, high Ki67 proliferation index, negativity of estrogen receptor and progesterone receptor were found to be predictors of DCISM in the univariate analysis (all P<0.05). And large diameter (≥2.7 cm)(OR 2.229,95% CI 1.505-3.301, P<0.001), high nuclear grade(OR 1.711,95%CI 1.018-2.875, P=0.043) and axillary lymph node metastasis(OR 4.140,95% CI 1.342-12.773, P=0.013) were found to be independent predictors of DCISM in the multivariate analysis (all P<0.05). Mammographically, the lesion types, the presence and distribution of calcification were statistically significant between DCIS and DCISM patients (χ 2=17.42, 9.65, 9.10, P<0.05). Up to 17.6% (80/455) of DCIS were occult leisions, and DCISM showed more lesions with calcification in mass, asymmetry, and architectural distortion (49.1%, 84/171). Grouped calcifications were usually associated with DCIS (41.5%, 120/289), while regional calcification were commonly found in DCISM (35.9%, 47/131). Conclusions:Lesions with calcification and regional calcification were more likely associated with DCISM on mammography. Large diameter (≥2.7 cm), high nuclear grade and axillary lymph node metastasis were found to be independent predictors of DCISM.

Correlation analysis between ATM gene polymorphism and susceptibility of sporadic breast cancer / 中国医师杂志

Objective:To analyze the relationship between ataxia telangiectasia mutated (ATM) single nucleotide polymorphism (SNP) at rs1801516 and rs1800054 and sporadic breast cancer (SBC) in Inner Mongolia.Methods:A total of 102 patients with SBC (72 Han and 30 Mongolian) who were admitted to the Affiliated Hospital of Inner Mongolia Medical University from January 2018 to September 2019 were prospectively collected as case group and 102 healthy women (72 Han and 30 Mongolian) during the same period as control group. 2 ml of venous blood was collected to extract DNA. According to the Single Nucleotide Polymorphism Database (dbSNP), the highly polymorphic sites rs1801516 and rs1800054 of ATM gene were selected. The polymerase chain reaction (PCR) and direct sequencing were used to detect the polymorphism of the two sites, and the correlation between the single nucleotide polymorphism of the two sites and the susceptibility of SBC in Inner Mongolia was analyzed. The potential association between clinicopathological factors and ATM gene polymorphism in patients with SBC in Inner Mongolia were explored.Results:GG, GA and AA genotypes were detected in rs1801516 locus of ATM gene. Only CC genotype was detected in the rs1800054 locus of ATM gene. There was no significant difference in the distribution of genotype frequency and allele frequency between Mongolian breast cancer group and Han breast cancer group, Mongolian control group and Han control group, Mongolian breast cancer group and Mongolian control group, Han breast cancer group and Han control group (all P>0.05). Logistic regression analysis showed that allele G was the susceptibility gene of SBC in Inner Mongolia ( OR: 1.775, 95% CI: 1.04-3.03, P=0.04). ATM rs1801516 polymorphism may be associated with increased risk of breast cancer in patients with mass diameter ≤2 cm and/or without lymph node metastasis (all P<0.05). Conclusions:The polymorphism of ATM gene rs1801516 and rs1800054 may not be significantly correlated with the risk of SBC in Inner Mongolia. The rs1801516 locus may be associated with increased risk of breast cancer in patients with mass diameter ≤2 cm and/or without lymph node metastasis. Gene G may be one of the susceptible genes of SBC in Inner Mongolia.

Bovine viral diarrhea virus NS4B protein interacts with 2CARD of MDA5 domain and negatively regulates the RLR-mediated IFN-ß production.

Bovine viral diarrhea virus (BVDV) is an important member of the family Flaviviridae and often causes immunosuppression. Previous studies have suggested that BVDV envelope protein Erns and the nonstructural autoprotease Npro can inhibit host innate immune responses. Herein, we found that BVDV NS4B, as a nonstructural protein necessary for replication, is involved in antagonizing the main RNA virus sensing pathway. Overexpression of BVDV NS4B protein significantly inhibited Sendai virus (SeV)-induced interferon-ß promoter activity, IFN-ß mRNA and IFN regulatory factor 3 (IRF3) phosphorylation levels. We also discovered that BVDV NS4B protein significantly inhibited RIG-I like receptor (RLRs)-mediated interferon-ß (IFN-ß) promoter activity and endogenous MDA5 mRNA levels. In addition, the BVDV NS4B protein directly interacts with N-terminal CARDs of MDA5, and co-localized with MDA5 or MDA5-2CARD in the cytoplasm. In summary, the results of this study indicate that the BVDV NS4B protein acts as an interferon-ß antagonist through inhibiting the MDA5-mediated signal transduction pathway. Our study provides an in-depth understanding of the molecular mechanisms of BVDV evading the host's natural immune response.

Value of digital breast tomosynthesis in diagnosis of radial lesions / 中华放射学杂志

Objective:To evaluate the diagnostic value of digital breast tomosynthesis (DBT) and digital mammography (DM) for radial lesions.Methods:The data of 76 patients (78 lesions) with radial lesions confirmed by operation and pathology on DBT between December 2016 and May 2020 in the Affiliated Hospital of Qingdao University were analyzed retrospectively. Taking pathological results as the gold standard, 78 lesions were divided into benign radial lesions ( n=46) and malignant radial lesions ( n=32), and their DBT features were compared. According to the standard of breast imaging report and data system (BI-RADS), the wheel-spoke structure, central density, overall size, central size and surrounding burr length of the two groups of radial lesions were compared on DBT. Results:The detection rates of DM and DBT for 78 radial lesions were 59.0% (46/78) and 100% (78/78), the difference had statistically significant ( P<0.05). The diagnostic accuracy rates of DM and DBT for 78 radial lesions was 65.2% (30/46) and 74.4% (58/78), the difference had no statistically significant ( P>0.05). The sensitivity, specificity, misdiagnosis rates, missed diagnosis rates of DM and DBT in the diagnosis of malignant radial lesions were 64.3%(18/28) and 84.4%(27/32), 66.7% (12/18) and 67.4%(31/46), 33.3%(6/18) and 32.6%(15/46), 35.7%(10/28) and 15.6%(5/32), respectively. The difference was not statistically significant ( P>0.05). There were significant differences in the overall size of lesions [18.0 (14.9, 29.2) mm, 26.5 (20.2, 34.9) mm], central size [3.5 (2.5, 4.5) mm, 4.5 (3.5, 5.5) mm] and peripheral burr length [(11±6) mm, (13±4) mm] between benign and malignant radial lesions on DBT ( P<0.05). When the central size of the lesion was 5 mm, there was significant difference in the distribution of benign and malignant radial lesions ( P<0.05), and when the overall size of the lesion was 2 cm, there was significant difference in the distribution of benign and malignant radial lesions ( P<0.05). Conclusion:DBT can improve the detection and diagnosis accuracy of radial lesions, and provide an important basis for clinicians to make surgical treatment decisions.

Analysis of Quality Status of National Medical Device Supervision and Inspection in 2019 / 中国医疗器械杂志

Summarize the quality status and variety quality change characteristics of the sampling products through the Summary and analysis, according to the results of the national medical device supervision and inspection in 2019. Put forward suggestions on the development of the medical device industry and supervisory measures. Thereby, further improve the level of the medical device and ensure the safety use of medical device.

miR-593 inhibits proliferation of colon cancer cells by down-regulating PLK1 / 南方医科大学学报

OBJECTIVE@#To explore the role of miR-593 in regulating the proliferation of colon cancer cells and the molecular mechanism.@*METHODS@#Bioinformatics analysis identified PLK1 as the possible target gene of miR-593. Luciferase assay was employed to verify the binding between miR-593 and PLK1, and qRT-PCR and Western blotting were used to verify that PLK1 was the direct target gene of miR-593. CCK-8 assay was performed to test the hypothesis that miR-593 inhibited the proliferation of colon cancer cells by targeting PLK1.@*RESULTS@#Luciferase assay identified the specific site of miR-593 binding with PLK1. Western blotting showed a significantly decreased expression of PLK1 in the colon cancer cells transfected with miR-593 mimics and an increased PLK1 expression in the cells transfected with the miR-593 inhibitor as compared with the control cells ( < 0.05). The results of qRT-PCR showed no significant differences in the expression levels of PLK1 among the cells with different treatments ( > 0.05). The cell proliferation assay showed opposite effects of miR-593 and PLK1 on the proliferation of colon cancer cells, and the effect of co-transfection with miR-593 mimic and a PLK1-overexpressing plasmid on the cell proliferation was between those in PLK1 over-expressing group and miR-593 mimic group.@*CONCLUSIONS@#miR-593 inhibits the proliferation of colon cancer cells by down-regulating PLK1 and plays the role as a tumor suppressor in colon cancer.

Association between Polymorphism of the BRCA2 Gene rs206115 Loci and Sporadic Breast Cancer / 中国医科大学学报

Objective To analyze the correlation between polymorphism of the BRCA2 gene rs206115 loci and sporadic breast cancer in Inner Mongolia. Methods We enrolled patients from the Affiliated Hospital of Inner Mongolia Medical University from December 2015 to December 2016 who underwent breast surgery and were confirmed by pathology, resulting in a total of 101 cases of primary sporadic breast cancer (case group) and benign breast diseases (control group). DNA was extracted from blood samples and analyzed using polymerase chain reaction (PCR) and direct sequencing methods for determining the BRCA2 gene rs206115 loci polymorphism. SPSS 17.0 was used for statistical analysis. Results In this experiment, regardless of whether the patients were Han or Mongolian, the rs206115 loci could be detected in 3 kinds of genotypes:AA, AG, and GG. The BRCA2 gene rs206115 locus gene polymorphism was not significantly different between the case and control groups (χ2=3.490, P = 0.175). The A allele frequency of the BRCA2 gene rs206115 loci in the case group was significantly increased compared to the control group (χ2=4.259, P = 0.039). Conclusion The A allele of rs206115 may be one of the susceptibility alleles in sporadic breast cancer in Mongolian and Han populations.

Dipyridyl pyrrolidine inhibits MDA-MB231 breast cancer cell cycle by inhibiting AKT-mTOR / 中国药科大学学报

@#To investigate the induction of cell cycle arrest of human breast cancer MDA-MB231 cells by Di-indolyl pyrrolidine(DIPRD), a pyrrolidine-derived spirooxindoles compounds. The cytotoxic effect of DIPRD on MDA-MB231 cells was detected by CCK-8 method. The cell cycle arrest of MDA-MB231 cells was detected by DAPI/EdU double-staining. Phosphorylation levels of AKT, mTOR, apoptosis-related proteins p53, MDM2, and DNA repair enzyme PARP levels were detected by Western blot. DIPRD inhibited the viability of MDA-MB231 cells by downregulating the number of EdU-positive cells, increase G1 phase and reduce cell number in S/G2 phase, down-regulated the p-AKT(Ser473), p-mTOR, p-p53, cyclin D1, CDK4, and the upregulated the p-AKT(Thr308), p-MDM2 and Cleaved-PARP levels were detected in a dose-dependent manner at 12. 5, 25, and 50 mg/mL. DIPRD may play a role in cell cycle arrest through AKT signaling pathway and induce cell apoptosis.

Comparison of diagnostic accuracy of digital breast tomosynthesis, digital mammography, and ultrasonography for the non-calcified ductal carcinoma in situ of the breast / 中华放射学杂志

Objective To compare the diagnostic value of digital breast tomosynthesis (DBT), digital mammography(DM),and ultrasonography(US)for the non-calcified ductal carcinoma in situ(DCIS) of the breast.Methods To retrospectively analyze the imaging and clinical data of ductal carcinoma in situ which was confirmed by surgical pathology and displayed as non-calcified lesions in mammography in 110 patients.DBT,DM and US were performed in all the 110 cases.The breast imaging report and data system (BI-RADS)classification and breast density classification were evaluated using the 5th edition of BI-RADS. In our study, BI-RADS 4B, 4C, and 5 were regarded to be in agreement with the pathologic findings, BI-RADS 1,2,3,and 4A were considered to be negative.BI-RADS c and d were classified as dense breasts, BI-RADS a and b were classified as fatty breasts.The imaging findings of the non-calcified ductal carcinoma in situ were evaluated.The differences in the detection rate and the diagnostic accuracy among the DBT,DM and US in all cases and in different breast density were compared using χ2 test. Results The detection rates of DBT,DM,and US for non-calcified DCIS in all cases were 84.5%(93/110),70.9%(78/110),95.5% (105/110).Pairwise comparisons among the three techniques showed statistically significant difference(P<0.05). The diagnostic accuracy of DBT, DM, and US were 70.0% (77/110), 44.5% (49/110), and 69.1% (76/110),respectively.The diagnostic accuracy of DBT and US were significantly higher than that of DM(P<0.01). Of the 110 patients, 89 patients were classified as dense breasts and non-dense breasts in the remaining 21 patients.The detection rates of DBT,DM,and US for non-calcified DCIS in dense breasts were 82.0%(73/89),65.2%(58/89),and 96.6%(86/89).Pairwise comparisons among the three techniques showed statistically significant difference(P<0.01).The diagnostic accuracy of DBT,DM,and US for non-calcified DCIS in dense breast were 65.2% (58/89), 38.2% (34/89) and 66.3% (59/89), respectively.The diagnostic accuracy of DBT and US were significantly higher than that of DM in dense breast(P<0.01).The detection rate and diagnostic accuracy for DBT,DM,and US in non-dense breasts were not statistically different(P>0.05).By DBT and DM,most cases of non-calcified DCIS presented as a mass lesion with an irregular shape, indistinct margin,and isodense composition.Conclusion US is more advantageous to the detection of the non-calcified DCIS and the non-calcified DCIS in the dense breast.

The correlation between S186N gene polymorphism and the premature infants with respiratory distress syndrome in Mongolian and Han ethnic / 中华急诊医学杂志

Objective To study the correlation between pulmonary surfactant protein C exon5 area's gene polymorphism and the premature infants with respiratory distress syndrome (RDS) among Mongolian and Han ethnic in Inner Mongolia District. Methods Fifty unrelated Mongolian RDS premature infants (28 weeks ≤ gestational age <37 weeks) were recruited as study group (31 male and 19 female), and another 50 unrelated Han ethnic RDS premature infants (28 weeks ≤ gestational age<37 weeks) were enrolled at the same time, as control group (27 male and 23 female).Polymerase chain reaction was used for gene polymorphism analysis and gene detection technology was employed to determine the sequence of SP-C gene exon5 area, respectively. At last, the difference in genotype frequency of SP-C gene exon 5 area C. 715G>A(S186 N) was compared between two groups. Results There were three genotypes could be checked out from SP-C gene exon 5 area C. 715G>A(S 186N)locus; namely GG,AA,AG types, and in study group, genotype frequencies of these three genotypes were 28％, 62％ and 10％, respectively, and G allele frequency was 33％, and A allele frequency was 67％. Genotype frequencies in control group were 78％, 10％ and 12％, respectively, and G allele frequency was 84％, A allele frequency was 16％. The A allele genotype frequency in study group at SP-C exon 5 area C. 715G>A(S186N) significantly higher than that in control group. There was statistically significant difference in alleles variations between two groups (χ2 = 53.300, P＜ 0.05). Conclusions SP-C exon 5 area C. 715G>A(S 186N)locus polymorphism related to Inner Mongolia Mongolian premature RDS. Individuals carrying SP-C exon 5 area C. 715G>A (S186N) A alleles have higher risk of suffering from RDS.

Cloning and expression of Staphylococcus aureus surface protein Isdb and its immune experiment in mice / 生物工程学报

In order to characterize the immunogenicity and immunoprotection of the Staphylococcus aureus (S. aureus) surface Isdb, we amplified Isdb gene from S. aureus Wood46 strain. The isdb gene was subsequently inserted into pET32a(+) vector and the recombinant plasmid was transformed into E. coli strain BL21. The recombinant Isdb was expressed and purified. Then, we immunized mice with the purified recombinant protein. The antibody level was measured by enzyme-linked immunosorbent assay. Finally, immunized mice were challenged with S. aureus strains Wood46 and HLJ23-1. These results showed that isdb gene sequences were highly conserved, and the recombinant Isdb was successfully expressed. The antibody titer in the immunized groups was increased significantly (P < 0.05) compared with the control, the protective rate of Isdb protein inducted by challenge with the two S. aureus stains Wood46 and HLJ23-1 was 62.5% and 75%, respectively. These results showed that the Isdb protein had high immunogenicity and immunoprotective capacity.

Immunogenicity of Staphylococcus aureus recombinant clumping factor A / 生物工程学报

In order to characterize the immunogenicity and immunoprotection of the Staphylococcus aureus (S. aureus) surface protein Clumping factor A (ClfA), we amplified clfa genes from S. aureus Newman strain, Wood46 strain and HLJ23-1. The clfa gene from Newman strain was subsequently inserted into pQE-30 vector and the recombinant plasmid was transformed into Escherichia coli strain M15 (pREP4). The recombinant ClfA protein was expressed and purified. Then, we immunized mice with the purified recombinant protein. The antibody level and the concentration of cytokines were measured by enzyme-linked immunosorbent assay. Finally, immunized mice were challenged with S. aureus Newman, Wood46 and HLJ23-1. These results suggested that clfa gene sequences were highly conserved, and the recombinant ClfA was expressed correctly with good antigenicity. The antibody titer and the concentration of cytokines in the immunized groups increased significantly (P < 0.05) compared with control, and the mice in the immunized groups were protected against the challenge strains to some extent. These results showed that the ClfA had high immunogenicity and immunoprotective potential.