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Objectives: Temozolomide (TMZ) is one of the most commonly used clinical drugs for glioblastoma (GBM) treatment, but its drug sensitivity needs to be improved.Gamabufotalin (CS-6), the primary component of the traditional Chinese medicine "ChanSu," was shown to have strong anti-cancer activity. However, more efforts should be directed towards reducing its toxicity or effective treatment doses.Methods: Target fishing experiment, Western blotting, PCR, confocal immunofluorescence and molecular cloning techniques were performed to search for possible downstream signalling pathways. In addition, GBM xenografts were used to further determine the potential molecular mechanisms of the synergistic effects of CS-6 and TMZ in vivo. Results: Mechanistic research revealed a negative feedback loop between ATP1A3and AQP4 through which CS-6 inhibited GBM growth and mediated the synergistic treatment effect of CS-6 and TMZ. In addition, by mutating potential amino acid residues of ATP1A3, which were predicted by modelling and docking to interact with CS-6, we demonstrated that abrogating hydrogen bonding of the amino acid Thr794 interferes with the activation of ATP1A3 by CS-6 and that the Thr794Ala mutation directly affects the synergistic treatment efficacy of CS-6 and TMZ. Conclusions:As the main potential target of CS-6, ATP1A3 activation critically depends on the hydrogen bonding of Thr794 with CS-6. The combination of CS-6 and TMZ could significantly reduce the therapeutic doses and promote the anti-cancer efficacy of CS-6/TMZ monotherapy.

Background Ovarian cancer (OC) is a major cause of cancer-related deaths among women. The aim of this study was to estimate and report data on the current burden of ovarian cancer worldwide over the past 30 years. Method Based on the data provided by GBD 2019, we collected and interpreted the disease data of ovarian cancer by incidence, mortality, disability-adjusted life-years (DALYs), and used corresponding age-standardized rates as indicators. Also, we categorized the data by attributed risk factors and captured deaths due to high fasting plasma glucose, occupational exposure to asbestos and high body-mass index, respectively. All outcomes in the study were reported using mean values and corresponding 95% uncertainty intervals (95% UI). Results Globally, there were 294422 (260649 to 329727) incident cases in 2019, and the number of deaths and DALYs were 198412 (175357 to 217665) and 5.36 million (4.69 to 5.95). The overall burden was on the rise, with a percentage change of 107.8% (76.1 to 135.7%) for new cases, 103.8% (75.7 to 126.4%) for deaths and 96.1% (65.0 to 120.5%) for DALYs. Whereas the age-standardized rates kept stable during 1990–2019. The burden of ovarian cancer increased with age. and showed a totally different trends among SDI regions. Although high SDI region had the declining rates, the burden of ovarian cancer remained stable in high-middle and low SDI regions, and the middle and low-middle SDI areas showed increasing trends. High fasting plasma glucose was estimated to be the most important attributable risk factor for ovarian cancer deaths globally, with a percentage change of deaths of 7.9% (1.6 to 18.3%), followed by occupational exposure to asbestos and high body mass index. Conclusions Although the age-standardized rates of ovarian cancer didn’t significantly change at the global level, the burden still increased, especially in areas on the lower end of the SDI range. Also, the disease burden due to different attributable risk factors showed heterogeneous, and it became more severe with age.

Background:To analyze and predict the possibility of post-operative recurrence in non-functioning pituitary adenoma (NFPA) patients, we investigated the clinical factors leading to tumor recurrence and built a nomogram predictive model based on these risk factors.Methods: A single-center retrospective study was performed. A total of 145 NFPA patients who underwent surgical treatment at Shenzhen People's Hospital from September 2013 to January 2019 were selected. Among them, 52 patients were diagnosed with recurrence of NFPA according to follow-up investigations.Binary logistic regression analysis was used to determine the significant risk factors. A nomogram model was then built to predict recurrence using these factors. Results:The univariate analysis and the binary logistic regression analysis showed that age, tumor size, cavernous invasion, sphenoid sinus invasion, and surgical extension were significant factors affecting tumor recurrence. We then built a nomogram model to predict post-operative recurrence in NFPA patients using these factors. The correlation analysis indicated that sphenoid sinus invasion [hazard ratio (HR) =13.14, 95%

This study evaluated the association between inflammatory diets as measured by the dietary inflammatory index (DII), and inflammation biomarkers, and the development of preeclampsia among the Chinese population. We followed the reporting guidelines of the STROBE statement for observational studies. A total of 466 preeclampsia cases aged over 18 years were recruited between March 2016 and June 2019, and 466 healthy controls were 1:1 ratio matched by age (± 3 years), week of gestation (± 1 week), and gestational diabetes mellitus. The energy-adjusted DII (E-DII) was computed based on dietary intake assessed using a 79-item semiquantitative food frequency questionnaire (FFQ). Inflammatory biomarkers were analyzed by ELISA kits. The mean E-DII scores were -0.65 ± 1.58 for cases and -1.19 ± 1.47 for controls (P value <0.001). E-DII scores positively correlated with IFN-γ (r s = 0.194, P value = 0.001) and IL-4 (r s = 0.135, P value = 0.021). After multivariable adjustment, E-DII scores were positively related to preeclampsia risk (P trend <0.001). The highest tertile of E-DII was 2.18 times the lowest tertiles (95% CI = 1.52, 3.13). The odds of preeclampsia increased by 30% (95% CI= 18%, 43%, P value <0.001) for each E-DII score increase. The preeclampsia risk was positively associated with IL-2 (OR = 1.07, 95% CI = 1.03, 1.11), IL-4 (OR = 1.26, 95% CI = 1.03, 1.54) and TGF-β (OR = 1.17, 95% CI = 1.06, 1.29). Therefore, proinflammatory diets, corresponding to higher IL-2, IL-4 and TGF-β levels, were associated with increased preeclampsia risk.

The fluorescent probe has become an important method for accurate detection of H 2 O 2 , with advantages of simple operation, high sensitivity, good selectivity, and real-time dynamic monitoring. This paper reviews the research progress in organic small-molecule fluorescent probe H 2 O 2 detection methods that are based on different recognition reactions. In addition, the application prospect of fluorescent probes in the detection of trace H 2 O 2 is anticipated.