Objective To research the action mechanism of Chinese FormulaXuetongling on MDA-MB-231 human breast cancer cell invasion.Methods Transwell Invasion assay was applied to investigate the inhibitory effects on cancer cell invasion ofXuetongling extract in different concentrations;MMP-9 secretion activity was detected by zymography assay after the treatment of XTL extract in MDA-MB-231;Western blot was used to detect the effect of XTL extract on MMP-9 protein expression in MDA-MB-231.ResultsXuetongling extract in different concentrations significantly suppressed the cell invasion, MMP-9 secretion and MMP-9 protein expression in dose dependent manner.Conclusion The inhibitory effect ofXuetongling on MDA-MB-231 cell invasion may be due to the down-regulation of both MMP-9 secretion and MMP-9 protein expression.

Objective: To compare the effectiveness of qualitative and quantitative fecal immunochemical tests (FIT) in identifying colorectal cancer, so as to provide insights into perfecting screening strategies for colorectal cancer. Methods: Participants in the Colorectal Cancer Screening Program for Key Populations in Zhejiang Province from May 2020 to December 2021 were recruited, and their demographic information, lifestyle and disease history were collected through a questionnaire survey. Qualitative or quantitative FIT along with a questionnaire-based risk assessment were employed as the initial screening tests. Individuals who were positive in any FIT or had high-risk assessment results were required to attend a subsequent colonoscopy examination. The positive rate, detection rate of colorectal cancer, positive predictive value and number of colonoscopies required were compared between qualitative and quantitative FITs, and stratified analyses by gender and age were conducted. Results: Totally 4 099 769 participants were included. The qualitative FIT group included 3 574 917 individuals, yielding a positive rate of 11.35%, a detection rate of 1.19%, a positive predictive value of 0.48% and 83.84 colonoscopies required to detect one cancer case. The quantitative FIT group involved 524 852 individuals, yielding a positive rate of 6.70%, a detection rate of 2.31%, a positive predictive value of 1.01% and 43.23 colonoscopies required to detect one cancer case. The quantitative FIT group showed significantly higher detection rate of colorectal cancer, higher positive predictive value and less number of colonoscopies required compared to the qualitative FIT group (all P<0.05). The same results were obtained after stratification by gender and age. Conclusion Compared to qualitative FIT, quantitative FIT improves the detection of colorectal cancer and reduces the workload of colonoscopy examinations, making it more suitable for colorectal cancer screening in large-scale populations.

OBJECTIVETo investigate the impact of high-dose microbubbles induced by high mechanical index myocardial contrast echocardiography (MCE) on vascular permeability and its recovery time in rats.

METHODSThirty male Wistar rats were randomized into 4 MCE groups (groups A-D) and a control group. In the MCE groups, Evans blue was injected at 10 s before MCE (A), immediately after the end of MCE (B), and at 5 min (C) and 20 min after the end of MCE (D). In the control group, the microbubbles and Evans blue were injected at the end of a 5-min ultrasound exposure. All the rats were sacrificed 5 min after Evans blue injection, and the content of Evans blue in the myocardium and the percentage of Evans blue leakage area were determined.

RESULTSThe percentage of Evans blue leakage area in groups A, B and C were significantly higher than that in the control group (P<0.05), while the percentage was similar between group D and the control group (P>0.05). Evans blue contents in groups A and B were significantly higher than that in the control group (P<0.05), but groups C and D showed comparable contents with the control group E (P>0.05). No significant changes of the heart rates and premature beat number were observed during and after MCE in these groups (P>0.05).

CONCLUSIONHigh mechanical index MCE and a high contrast dose may induce increased microvascular leakage in rats, and the vascular permeability can recover in 20 min after MCE.

Animals ; Capillary Permeability ; drug effects ; Contrast Media ; pharmacology ; Coronary Vessels ; physiopathology ; Echocardiography ; Male ; Microbubbles ; Rats ; Rats, Wistar

Objective:To study the specific mechanism of LINC01018 involved in the pathogenesis of colon cancer.Methods:The expression of LINC01018 in colon cancer tissues and cells and normal colon tissues and cells were detected by real time fluorescence quantitative polymerase chain reaction (qRT-PCR). HT-29 cell line which overexpresses LINC01018 stably was established. RNA binding protein immunoprecipitation (RIP) assay was used to detect the interaction between LINC01018 and E2F1 protein. Dual luciferase assay was used to detect the regulatory effect of E2F1 on CDK6 promoter. The expression of E2F1 or CDK6 was up-regulated in HT-29 cell line which overexpresses LINC01018, then the proliferation, invasion and migration of HT-29 cells and the expression of CDK6 and matrix metalloproteinase-2 (MMP-2) in HT-29 cells were detected by cell counting method (CCK-8) assay, Transwell assay and Western blot.Results:The expression of LINC01018 was abnormally low in colon cancer tissues and cells. The result of RIP assay showed that LINC01018 interacted with E2F1 protein. The result of dual luciferase assay showed that E2F1 protein could enhance the efficiency of CDK6 promoter, and E2F1 had a positive regulatory effect on CDK6. Overexpression of LINC01018 could attenuate the positive regulatory effect of E2F1 on CDK6. Up-regulation of E2F1 or CDK6 expression could attenuate the effects of LINC01018 overexpression on the proliferation, invasion, migration and expression of CDK6 and MMP-2 in HT-29 cells.Conclusions:The expression of LINC01018 was abnormally low in colon cancer tissues and cells. LINC01018 may regulate the proliferation, invasion and migration of HT-29 cells through E2F1/CDK6/MMP-2 axis, and participate in the pathogenesis of colon cancer.

Gene editing tools with nucleases as the main component have now implemented programmable targeted mutagenesis or insertion or deletion of mammalian genomes.From zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), CRISPR/Cas system to safer and more accurate Cas9 fusion protein gene editing tools and other nuclease gene editing tools, this paper systematically describes the development and evolution of gene editing, with detailed introduction to the development and optimization of next-generation gene editing tools, and a prospect of the clinical application of and challenges for gene editing tools.

Objective:To evaluate biological dose and retrospective biodosimetry of a case of large area back skin injury caused by suspected interventional procedure.Methods:Peripheral blood from the patient was collected at about 7 months after interventional procedure, and the chromosomal aberrations in peripheral blood cells were analyzed to evaluate the retrospective biodosimetry using the correction factor of dose estimation, Dolphin′s model and Qdr method, respectively. Results:Based on the amounts of semi-automated dic and manually detected dic plus ring, the whole-body average absorbed dose of the victim was estimated to be 0.68-0.95 Gy by four different dose response curves. Over dispersion of dic or dic plus ring was also detected, and the efficiency of dose assessment was obviously increased using dic semi-automatic detection. Based on three different retrospective biodosimetry models, the estimated average absorbed dose was further corrected to be between 1.80-2.86 Gy, which was consistent with clinical diagnosis of degree Ⅳ radiation skin injury.Conclusions:A case of suspected radiation skin injury was confirmed by chromosomal aberration analysis and it’s biodosimetry was reconstructed, suggesting that the unstable chromosomal aberration analysis may be applicable to assess the retrospective biodosimetry of non-uniform local radiation exposure.