Maintenance use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) and prostate cancer risk

Background: Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) may have a preventive effect against prostate cancer. However, evidence is limited and still controversial, especially considering non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs). Methods: Swedish nationwide population-based cohort study including all long-term (>= 180 days) adult male users of aspirin (n = 419,931) or NSAIDs (n = 223,437) followed from the first dispense date until the first cancer diagnosis, death or 31 December 2012, whichever occurred first. The risk of prostate cancer was measured as standardized incidence ratios (SIR) and 95% confidence intervals (CI), assessing duration of use, age and concomitant statins intake, comparing to the general male background population of the same age in Sweden. Results: The overall SIR suggests that maintenance use of aspirin decreases the risk of prostate cancer (SIR = 0.87, 95% CI 0.85-0.88), in particular if used >= 5 years (SIR = 0.31, 95% CI 0.30-0.32). The overall risk was decreased (SIR = 0.87, 95% CI 0.85-0.90) among other NSAIDs users, and again in particular among longer-term users (>= 3 years) with SIR = 0.58 (95% CI 0.53-0.63). When statins users were excluded from all aspirin users, there was no remaining association with prostate cancer (SIR = 0.99, 95% CI 0.96-1.02), only if taken >= 5 years (SIR = 0.31, 95% CI 0.29-0.34). For non-aspirin NSAIDs users, the protective effect remained after exclusion of statins users (SIR = 0.92, 95% CI 0.88-0.95). Conclusions: This population-based cohort study provides evidence for a protective effect of aspirin and other NSAIDs against prostate cancer, in particular for longer durations of use, yet concomitant use of statins strongly influences the risk among aspirin users

A study of two major challenges in prostate cancer : effective chemo-prevention and overcoming resistance to hormonal and chemotherapy

For men, over the course of a lifetime the risk of developing prostate cancer is 1 in 9. Both the illness itself and treatment affect quality of life in multiple aspects, including urinary problems, pain, and sexual dysfunction. Current clinical challenges in this field include: inevitable drug resistance to treatments, lack of accurate diagnostic and prognostic biomarkers, as well as no common chemoprevention strategies. The aim of this thesis is therefore to identify transcript alternations associated with drug resistance (Study I and Study II), to evaluate potential drug targets for prostate cancer treatment (Study III), and to estimate the preventive effect of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) against prostate cancer (Study IV). Castration resistance and docetaxel resistance are two significant issues that arise during prostate cancer disease progression. We employed next generation RNA sequencing technology to compare hormone-resistant (Study II) and docetaxel-resistant (Study I) vs respective sensitive cell lines, aiming to discover a potential drug target with the capability of prolonging the duration of hormone and docetaxel treatments before the cancer cells becoming resistant. The results showed that a variety of transcript alterations were obtained during resistance development, including mutations, altered gene expressions, and fusion transcripts. These alterations might be associated with drug resistance in prostate cancer. As a rationale for Study III, we hypothesized that proteins that have never been reported as mutated in prostate cancer might play an important role in cancer progression through their essential function of maintaining cellular stability in cancer cells. Upon mutation, these genes would induce severe cellular instability such that the cells could not survive, and these cells would be erased through natural selection during cancer growth. In Study III, we therefore evaluated a non-mutated protein in prostate cancer, GPR89A, as a potential drug target with possible anti-cancer function. Low-dose aspirin has been recommended by the U.S. Preventive Services Task Force (USPSTF) to prevent cardiovascular disease and colorectal cancer. However, results published in scientific studies are controversial regarding prostate cancer. In Study IV, we assessed whether maintenance use of aspirin or other NSAIDs could reduce the risk of prostate cancer. Based on data from the Swedish Cancer Register, the Swedish Prescribed Drug Register and the Swedish Causes of Death Register (2005-2012), we conducted a nationwide cohort study and found a protective effect of aspirin and other NSAIDs against prostate cancer, especially after long-term intake. In sum, this thesis identified or assessed alternative methods against prostate cancer through exploring molecular approaches to develop more effective treatment methods, and by attempting to reduce the prevalence of cancer cases through chemoprevention

Room-temperature ammonia sensor based on ZnO nanorods deposited on ST-cut quartz surface acoustic wave devices

Using a seed layer-free hydrothermal method, ZnO nanorods (NRs) were deposited on ST-cut quartz surface acoustic wave (SAW) devices of ammonia sensing at room-temperature. For a comparison, a ZnO film layer of 30 nm thick was also coated onto ST-cut quartz SAW device using a sol–gel and spin-coating technique. The ammonia sensing results showed that the sensitivity, repeatability and stability of the ZnO NRs coated SAW device were superior to those of the ZnO film coated SAW device due to the large surface-to-volume ratio of the ZnO NRs

Surface acoustic wave ammonia sensor based on SiO2-SnO2 composite film operated at room temperature

Sensitive thin film layers of SnO2, SiO2 and SiO2-SnO2 were deposited on a SAW resonator using sol-gel method and spin coating techniques. Their ammonia-sensing performance operated at room temperature was characterized and their sensing mechanisms were comprehensively studied. When exposed to ammonia, the sensors made of SnO2 and SiO2-SnO2 films exhibit positive frequency shifts, whereas the SiO2 film sensors exhibit a negative frequency shift. The positive frequency shift is related to the dehydration and condensation of hydroxyl groups, which make the films stiffer and lighter. The negative frequency shift is mainly caused by the increase of mass loading due to the adsorption of ammonia. The gas sensor based on SiO2-SnO2 film shows a positive frequency shift of 631 Hz when it is exposed to ammonia with a low concentration of 3 ppm, and it also shows good repeatability and stability, as well as a good selectivity to ammonia compared with gases of C6H14, C2H5OH, C3H6O, CO, H2, NO2, and CH4

Room temperature magnetic phase transition in an electrically-tuned van der Waals ferromagnet

Finding tunable van der Waals (vdW) ferromagnets that operate at above room temperature is an important research focus in physics and materials science. Most vdW magnets are only intrinsically magnetic far below room temperature and magnetism with square-shaped hysteresis at room-temperature has yet to be observed. Here, we report magnetism in a quasi-2D magnet Cr1.2Te2 observed at room temperature (290 K). This magnetism was tuned via a protonic gate with an electron doping concentration up to 3.8 * 10^21 cm^-3. We observed non-monotonic evolutions in both coercivity and anomalous Hall resistivity. Under increased electron doping, the coercivities and anomalous Hall effects (AHEs) vanished, indicating a doping-induced magnetic phase transition. This occurred up to room temperature. DFT calculations showed the formation of an antiferromagnetic (AFM) phase caused by the intercalation of protons which induced significant electron doping in the Cr1.2Te2. The tunability of the magnetic properties and phase in room temperature magnetic vdW Cr1.2Te2 is a significant step towards practical spintronic devices.Comment: 18 pages, 4 figure

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke

Importance It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023.InterventionsEligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability.Trial RegistrationChiCTR.org.cn Identifier: ChiCTR210005172