Objective To compare the clinicopathological characteristics between primary and contralateral cancers in patients with metachronous bilateral breast cancer (MBBC) who carried a BRCA1/2 germline pathogenic variant. Methods A total of 496 BRCA1/2 carriers with primary unilateral breast cancer were included (196 with BRCA1 and 300 with BRCA2). Clinicopathological information of patients was collected, and the median follow-up for the entire cohort was 10.4 years (0.4-20.8 years). Results Among all patients, 31 (15.8%) of the 196 BRCA1 carriers and 49 (16.3%) of the 300 BRCA2 carriers had MBBC, respectively. Among the 31 BRCA1 carriers who developed MBBC, the proportion of triple-negative breast cancer (TNBC) in primary cancer and contralateral cancer was 61.3% and 67.7%, respectively. If the primary cancer of BRCA1-mutated MBBC was TNBC, the probability of the contralateral breast cancer with TNBC was 89.5% (17/19), which was significantly higher than that if the primary cancer was non-TNBC (33.3%, 4/12) (P=0.004). Among the 49 BRCA2 carriers who developed MBBC, the predominant molecular phenotype of the primary and contralateral cancers was HR+ & HER2- (77.6% and 67.3%, respectively; P=0.53). Conclusion Approximately 60% of BRCA1 carriers exhibit TNBC. If a BRCA1 carrier with a TNBC primary breast cancer had an MBBC, the probability of the contralateral breast cancer being TNBC phenotype is almost 89.5%.

Objective:To investigate the correlations of stable chronic obstructive pulmonary disease(COPD)with inositol 1, 4, 5-trisphosphate 3-kinase C(ITPKC)and phospholipase C-like 1 protein(PLCL1)single nucleotide polymorphisms(SNPs)in the Han elderly population in Ningxia.Methods:A case-control study was conducted.A total of 250 elderly patients with stable COPD were enrolled and divided into the COPD-related pulmonary hypertension(PH)group(n=103)and the COPD non-PH group(n=147). During the same period, 127 healthy elderly Han subjects were included as the control group.The ITPKC gene SNPs and the PLCL1 gene SNP were detected, and differences in alleles and genotype frequencies were compared between the groups.Results:The allele and genotype frequency distributions of rs2288450 and rs9789480 showed statistical differences between the COPD group and the control group(χ 2=6.09, 5.18, 30.14 and 32.89, P=0.048, 0.020, <0.001, <0.001). There was no difference in the allele and genotype frequency distributions of the ITPKC gene SNPs rs2290692 and rs17713068 between the control group and the COPD group(all P>0.05). The allele and genotype frequency distributions of rs9789480 showed differences between the COPD non-PH group and the COPD-PH group(χ 2=94.50 and 72.76, both P<0.001). There was no significant difference in the allele and genotype frequency distributions of rs2290692, rs17713068, rs2288450 between the COPD-PH group and the COPD non-PH group(all P>0.05). Conclusions:The ITPKC gene SNP rs2288450 CA and AA genotypes and A allele can reduce the incidence of COPD and may be a protective factor for COPD in the elderly.The PLCL1 gene SNP rs9789480 CA and AA genotypes and A allele can reduce the incidence of COPD and COPD-PH and may be a protective factor for COPD and COPD-PH in the elderly.

Objective:To study the effect of p38 mitogen-activated protein kinase (MAPK) gene silencing on expression of apoptotic genes and oncogenes in hepatocytes treated with PM 2.5. Methods:From June to September 2019, according to the p38MAPK gene mRNA sequence provided by GenBank, three interfering sequences were designed and synthesized, ligated into PLVX-shRNA2-puro after annealing, and the recombinant lentiviral vector was transfected into L02 hepatocytes. The p38MAPK silencing cells were identified by real-time fluorescent quantitative PCR and western blotting. The normal L02 cells and p38MAPK silencing cells were treated with 50 μg/mL PM 2.5 water soluble solution, 10 μmol/L positive control Cr 6+, and a blank control group was set up, the treatment time was 24 h. The mRNA levels of oncogenes (c-fos, c-myc, k-ras) , tumor suppressor gene (p53) and apoptotic genes (Caspase-3, Caspase-8, Caspase-9) were detected by real-time PCR. The protein levels of oncogenes and apoptotic genes were detected by Western blotting. Results:The expression levels of p38MAPK mRNA and protein in p38MAPK gene silencing cells were significantly lower than those in L02 hepatocytes ( P<0.05) , and the p38MAPK gene silencing cell line was successfully constructed. Compared with the blank control group, the expression levels of the oncogenes c-fos, c-myc, k-ras and the apoptosis genes Caspase-3, Caspase-8 and Caspase-9 increased, the expression level of tumor suppressor gene p53 decreased in the L02 hepatocyte group treated with PM 2.5 water soluble matter, and the differences were statistically significant ( P<0.05) . Compared with the L02 hepatocytes group treated with PM 2.5 water soluble matter, the expression levels of the oncogenes c-fos, c-myc, k-ras and apoptosis genes Caspase-3, Caspase-8 and Caspase-9 decreased, the expression level of tumor suppressor gene p53 increased in the p38MAPK gene silencing cells group treated with PM 2.5 water soluble matter, and the differences were statistically significant ( P<0.05) . Conclusion:PM 2.5 has effects on the expression of oncogenes, tumor suppressor genes and apoptotic genes in L02 hepatocytes, while p38MAPK gene silencing can inhibit the effects of PM 2.5 on L02 hepatocytes.

Objective:To study the effect of p38 mitogen-activated protein kinase (MAPK) gene silencing on expression of apoptotic genes and oncogenes in hepatocytes treated with PM 2.5. Methods:From June to September 2019, according to the p38MAPK gene mRNA sequence provided by GenBank, three interfering sequences were designed and synthesized, ligated into PLVX-shRNA2-puro after annealing, and the recombinant lentiviral vector was transfected into L02 hepatocytes. The p38MAPK silencing cells were identified by real-time fluorescent quantitative PCR and western blotting. The normal L02 cells and p38MAPK silencing cells were treated with 50 μg/mL PM 2.5 water soluble solution, 10 μmol/L positive control Cr 6+, and a blank control group was set up, the treatment time was 24 h. The mRNA levels of oncogenes (c-fos, c-myc, k-ras) , tumor suppressor gene (p53) and apoptotic genes (Caspase-3, Caspase-8, Caspase-9) were detected by real-time PCR. The protein levels of oncogenes and apoptotic genes were detected by Western blotting. Results:The expression levels of p38MAPK mRNA and protein in p38MAPK gene silencing cells were significantly lower than those in L02 hepatocytes ( P<0.05) , and the p38MAPK gene silencing cell line was successfully constructed. Compared with the blank control group, the expression levels of the oncogenes c-fos, c-myc, k-ras and the apoptosis genes Caspase-3, Caspase-8 and Caspase-9 increased, the expression level of tumor suppressor gene p53 decreased in the L02 hepatocyte group treated with PM 2.5 water soluble matter, and the differences were statistically significant ( P<0.05) . Compared with the L02 hepatocytes group treated with PM 2.5 water soluble matter, the expression levels of the oncogenes c-fos, c-myc, k-ras and apoptosis genes Caspase-3, Caspase-8 and Caspase-9 decreased, the expression level of tumor suppressor gene p53 increased in the p38MAPK gene silencing cells group treated with PM 2.5 water soluble matter, and the differences were statistically significant ( P<0.05) . Conclusion:PM 2.5 has effects on the expression of oncogenes, tumor suppressor genes and apoptotic genes in L02 hepatocytes, while p38MAPK gene silencing can inhibit the effects of PM 2.5 on L02 hepatocytes.

OBJECTIVETo observe the clinical efficacy differences between different needling methods for dry eye syndrome.

METHODSSixty patients of dry eye syndrome were randomly divided into an observation group and a control group, 30 cases (60 eyes) in each group. Shangjingming (Extra), Xiajingming (Extra), Tongziliao (GB 1), Cuanzhu (BL 2), Fengchi (GB 20), Hegu (LI 4), Sanyinjiao (SP 6), Taixi (KI 3) and Taichong (LR 3) were selected in the two groups. The control group was treated with conventional acupuncture, while the observation group was treated with guiding-acupuncture. Electroacupuncture (EA) was used at bilateral Tongziliao (GB1) and Cuanzhu (BL 2), 30 min per treatment. The treatment was given three times per week. Totally 1-month treatment (12 treatments) was given. The eye symptom score, breakup time of tear film (BUT), Schirmer Ⅰ test (SⅠT) and visual analogue scale (VAS) score were compared before and after treatment in the two groups. The clinical efficacy was compared between the two groups.

RESULTSCompared before treatment, the eye symptom score, BUT, SⅠT and VAS score were improved after treatment in the two groups (all<0.001); the improvements of eye symptom score and SⅠT in the observation group were superior to those in the control group (both<0.05). The differences of BUT and VSA score between the two groups were not significant (both>0.05). The total effective rate was 86.7% (52/60) in the observation group, which was superior to 73.3% (44/60) in the control group (<0.05). .

CONCLUSIONThe conventional EA and guiding-acupuncture combined with EA are both effective for dry eye syndrome, and the efficacy of guiding-acupuncture combined with EA is superior to that of conventional EA.

Objective To evaluate the safety and efficacy of the combined treatment with an optimized intense pulsed light (IPL) and a non-ablative fractional laser (NAFL) for facial rejuvenation.Methods A prospective,split-face,randomized,controlled study was conducted.A total of 22 testees with facial photoaging,who aged from 35 to 55 years,were enrolled into this study from the Department of Dermatology of Peking University First Hospital between March and June in 2017.By a random number table,the two sides of each testee's face were randomized to receive combined treatment with optimized IPL immediately followed by non-ablative 1 565 nm Erbium:Glass fractional laser (combined treatment group) or non-ablative 1 565 nm Erbium:Glass fractional laser alone (NAFL group) once every month for 3 sessions.Before the treatment,60 and 90 days after the treatment (1 month after the second and third treatment respectively),photos of the treatment regions were taken,skin physiology parameters (including skin melanin,erythema indices,water content of the stratum corneum,transepidermal water loss [TEWL],skin flexibility and glossiness) were measured,and subjective and objective clinical evaluation was carried out.After each treatment,adverse reactions were assessed by two dermatologists independently,including facial erythema,swelling and crusting,desquamation,pigmentation and pains.Results During the treatment course,1 testee dropped out due to pains,another 1 testee dropped out for personal reasons,and 20 testees completed the treatment and follow-up.The combined treatment group showed significantly decreased melanin indices on days 60 and 90 (152.9 ± 36.9 and 155.0 ± 38.1,respectively) compared with that before the treatment (168.4 ± 41.3,F =5.321,P ＜ 0.05).On day 60,the melanin index was significantly lower in the combined treatment group than in the NAFL group (159.4 ± 35.3,P ＜ 0.05).However,the melanin indices on days 60 and 90 in the NAFL group (159.4 ± 35.3,156.7 ± 36.3) did not significantly differ from that before the treatment (165.9 ± 35.4,P ＞ 0.05).No significant difference was observed between the pre-and post-treatment erythema indices in either of the two groups (both P ＞ 0.05).The water content of the stratum corneum on days 60 and 90 significantly increased compared with that before the treatment in both the combined treatment group (F =21.795,P ＜ 0.001) and NAFL group (F =21.798,P ＜ 0.001),while the TEWL on days 60 and 90 significantly decreased compared with that before the treatment in both the combined treatment group (F =8.848,P =0.001) and NAFL group (F =5.833,P ＜ 0.05).However,there were no significant differences in either of the water content of the stratum corneum or TEWL on days 60 and 90 between the two groups (P ＞ 0.05).On days 60 and 90,the combined treatment group and NAFL group both showed significantly increased skin flexibility (P＜ 0.05,0.001,respectively) and glossiness (both P ＜ 0.001) compared with those before the treatment.On day 90,the skin glossiness in the combined treatment group was higher than that in the NAFL group (P ＜ 0.05).The short-term adverse reactions included transient pain,erythema and swelling which lasted 2-3 days,and slight desquamation.The main adverse reaction was mild local pigmentation,which lasted 2-3 months and then subsided gradually.Conclusion The 3 sessions of treatment with an optimized IPL immediately followed by a 1 565 nm NAFL is clinically superior to those with the NAFL alone for improving the facial pigmentation and skin glossiness,and the adverse reactions are usually transient and mild.

OBJECTIVETo study the potential association of DNA oxidation and DNA methylation, in vitro cultured cells were exposed to different doses of H2O2, 8-oxo-dG formation, cell DNA 5-mC contents were analyzed to explore the time- dose-response relationship of DNA oxidation and DNA methylation.

METHODSA549 cells were exposed to different doses of H2O2, 8-oxo-dG formation and cell genomic DNA 5-mC contents were analyzed by a high-performance liquid chromatography system and high performance capillary electrophoresis (HPCE), respectively.

RESULTSH2O2 induced the formation of 8-oxo-dG and 5-mC in different characteristics, it need at least 10 days for significant changes in the level of DNA methylation, whereas under the same conditions, changes in the level of DNA oxidation cast only 12 hours. H2O2 induced decreased levels of DNA methylation in A549 cells in a dose-dependent manner. In a certain range of time and dose, it showed a negative correlation between DNA oxidation and DNA methylation.

CONCLUSIONThe study suggests that oxidative DNA could lead to reduced levels of DNA methylation, DNA oxidation may affect the regulation of cellular methylation mechanisms, in the course of chemical mutagenesis, DNA oxidation may be an earlier important molecule event than DNA methylation.

Cell Line ; DNA ; chemistry ; DNA Damage ; DNA Methylation ; Deoxyguanosine ; analogs & derivatives ; chemistry ; Humans ; Hydrogen Peroxide ; toxicity ; Oxidative Stress