ABSTRACT
ObjectiveAutonomic dysfunction is a common and serious complication in patients with early chronic kidney disease （CKD）. Sweat gland dysfunction is an initial sign of autonomic dysfunction. Electrochemical skin conductance （ESC） measurement by reverse iontophoresis and chronoamperometry to assess sweat gland function may detect patients with mild renal insufficiency in healthy population for early intervention and treatment to delay further deterioration of renal function. MethodsAn EZSCAN score （0~100） was calculated using a proprietary algorithm based on the chronoamperometry analysis. A total of 6 661 subjects who received physical examination from the physical examination center of the Second Affiliated Hospital of Zhejiang University School of Medicine from January to October 2020 were enrolled， including 2 075 （31.15%） subjects with reduced renal function （eGFR < 90 mL·min-1·1.73 m-2） as the case group and 4 586 （68.85%） subjects with normal renal function （90 mL·min-1·1.73 m-2≤ eGFR ≤120 mL·min-1·1.73 m-2） as the control group. Lasso regression was used to screen covariates， and the relationship between the risk score and eGFR was analyzed by loess curve and logistic regression. ResultsAfter multivariate adjustment， the risk score was correlated with the risk of eGFR decline. Compared with the group with the lowest risk value （Q1<24）， the OR（95%CI ）of Q2 （25-27）， Q3 （28-47）， and Q4 （48-75） were 1.85 （1.55， 2.21）， 2.53 （2.13， 3.00）， 2.49 （2.13， 2.93）， respectively. The maximum area under the ROC curve is 0.75（0.74，0.76）， the sensitivity is 73.98%， the specificity is 63%， the positive predictive value is 47.49%， the negative predictive value is 84.25%， and the Youden index is 0.369 72， the optimal cutoff value is 25. ConclusionsEZSCAN could be a useful screening tool to identify healthy individuals at increased risk of renal function decline， and the one with an EZSCAN score of more than 25% should undergo diagnostic laboratory testing.
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Aim To investigate the hepatotoxicity of rutecarpine(RUT)by using high-content screening technology.Methods HepG2 cells were exposed to different concentrations of RUT for different time, then cell viability was detected by MTT method.Cell count, nucleus injury, mitochondrial membrane potential(MMP), reactive oxygen species(ROS), internal flow of calcium, cell membrane integrity(DIR)were measured by high-content screening technology.The activation of MAPK, NF-κB and JAKs-STATs was assayed by high-content screening technology.The apoptosis was detected by flow cytometry.Results The viability was significantly reduced by 100 μmol·L-1 RUT(P<0.01)after HepG2 cell exposure to RUT for 24 h, the nuclear area decreased and the nuclear morphology was uneven, and after 48 h, the cell count was significantly reduced(P<0.01), the early apoptosis was detected(P<0.01).After HepG2 cell exposure to RUT for 6 h, the levels of ROS and internal flow of calcium significantly increased(P<0.01), and the cell membrane integrity was obviously damaged(P<0.01).After exposure to 100 μmol·L-1 RUT for 24 h, the phosphorylation of ERK, JNK, STAT3 and p38 significantly increased(P<0.01, P<0.05), but there was no significant change in total protein level.The expression of c-Jun and c-Fos was up-regulated at 3 h(P<0.01), and at 3h time point, the phosphorylation of NF-κB p65 significantly increased(P<0.01), but nuclear translocation was not significant.Conclusions Under certain conditions, RUT shows cytotoxicity on HepG2 cells, and its toxic mechanism is mainly related to injury caused by oxidative stress and inflammatory response.
ABSTRACT
Aim To investigate the hepatotoxicity of rutecarpine(RUT)by using high-content screening technology.Methods HepG2 cells were exposed to different concentrations of RUT for different time, then cell viability was detected by MTT method.Cell count, nucleus injury, mitochondrial membrane potential(MMP), reactive oxygen species(ROS), internal flow of calcium, cell membrane integrity(DIR)were measured by high-content screening technology.The activation of MAPK, NF-κB and JAKs-STATs was assayed by high-content screening technology.The apoptosis was detected by flow cytometry.Results The viability was significantly reduced by 100 μmol·L-1 RUT(P<0.01)after HepG2 cell exposure to RUT for 24 h, the nuclear area decreased and the nuclear morphology was uneven, and after 48 h, the cell count was significantly reduced(P<0.01), the early apoptosis was detected(P<0.01).After HepG2 cell exposure to RUT for 6 h, the levels of ROS and internal flow of calcium significantly increased(P<0.01), and the cell membrane integrity was obviously damaged(P<0.01).After exposure to 100 μmol·L-1 RUT for 24 h, the phosphorylation of ERK, JNK, STAT3 and p38 significantly increased(P<0.01, P<0.05), but there was no significant change in total protein level.The expression of c-Jun and c-Fos was up-regulated at 3 h(P<0.01), and at 3h time point, the phosphorylation of NF-κB p65 significantly increased(P<0.01), but nuclear translocation was not significant.Conclusions Under certain conditions, RUT shows cytotoxicity on HepG2 cells, and its toxic mechanism is mainly related to injury caused by oxidative stress and inflammatory response.
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The incidence of colorectal cancer is high threatening human health. About 60％～70％cases of CRC are derived from colorectal polyps, which can be treated by endoscopic electrotomy to prevent the possibility of canceration. Therefore, in the prevention and treatment of CRC, the role of screening is of great significance. CRC screening methods include the most commonly used fecal occult blood test ( FOBT ) and the more sensitive fecal immunochemical test (FIT), cost-effective fiber sigmoidoscopy and colonoscopy, CT colonoscopy (CTC), and fecal DNA testing and immature CRC hematology screening. In this paper, the CRC screening technologies were reviewed, including the principles, characteristics and the latest research progress to provide a theoretical basis for the application and development of CRC screening technology.
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Breast cancer is the most common malignant tumor in women. With the development of cell biology and molecular bio-technology, great progress has been made in the study of the pathogenesis of breast cancer. Familial breast cancer is closely related to the mutation of susceptible genes. Selected susceptible genes of breast cancer can be grouped into three categories: high-, medium-, and low-penetrance susceptible genes. The means of identifying the high-risk sites of pathogenic mutation and genetic polymorphism is the focus of research on the genetic predisposition of breast cancer.
ABSTRACT
Breast cancer is the first malignant tumor of women, and the incidence is still rising. Although the overall survival rate of breast cancer is high, the difference in prognosis is significant with different stage. Finding the patients at early stage and commencement of therapy timely by breast cancer screening is the key to reduce the incidence and improve the survival rate. At present, clinical breast examination, ultrasonography, mammography and MRI are still the most common methods for breast cancer screening, but in view of the specific technology and specific population it remains controversial as to which techniques are the best, especially the value of ultrasonography still needs to be confirmed in randomized clinical trials. With the constant improvement of technologies and programs, the breast cancer screening work will be more standardized and optimized.
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Traditional Chinese medicines (TCM) is one of the most important sources of new drugs.The rapid development of modern science and technology has brought new opportunities for TCM.Admittedly,new academic theory is getting into a golden period of innovation.Key technologies that enbody TCM features and adapt to modern drug-screening requirements are urgently needed.After five years' endeavor,the authors' group has made great progress in the new theories and methodologies for the discovery of bioactive compounds from TCM.In this review,a total of five key technologies:library-bioactivity-structure integration,biological and chemical fishing technology,ligand-and receptor-based virtual screening,profile-bioactivity relationship and the technology for discovering bioactive equivalent combinatorial components (BECCs),were introduced.In the text,several valuable demonstrations over the TCM-based drug discovery were provided,for uncovering the scientific basis of TCM and accelerating the process of TCM modernization.
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Anticancer targets of cryptotanshinone were evaluated and rapidly forecasted with PharmMapper, a reverse pharmacophore-based screening platform, as well as drug target databases, including PDTD, DrugBank and TTD. The pathway analyses for the collection of anticancer targets screened were carried out based on the KEGG pathway database, followed by the forecast of potential pharmacological activities and pathways of the effects of cryptotanshinone, and verification of some of the targets screened using whole cell tests. The results showed that a total of eight targets with anticancer potential were screened, including MAP2K1, RARα, RXRα, PDK1, CHK1, AR, Ang-1 R, and Kif11. These targets are mainly related to four aspects of the cancer growth: the cell cycle, angiogenesis, apoptosis, and androgen receptor. The cell tests showed that cryptotanshinone can inhibit the viability of human hepatoma cells SMMC-7721, which is related to the reduction of expression of MAP2K1 mRNA. This method provides a strong clue for the study of the anticancer effects and mechanisms of action of cryptotanshinone in the future.