Ischemic stroke is a cerebrovascular disease associated with high mortality and disability rates. Since the inflammation and immune response play a central role in driving ischemic damage, it becomes essential to modu...Ischemic stroke is a cerebrovascular disease associated with high mortality and disability rates. Since the inflammation and immune response play a central role in driving ischemic damage, it becomes essential to modulate excessive inflammatory reactions to promote cell survival and facilitate tissue repair around the injury site. Various cell types are involved in the inflammatory response, including microglia, astrocytes, and neutrophils, each exhibiting distinct phenotypic profiles upon stimulation. They display either proinflammatory or anti-inflammatory states, a phenomenon known as ‘cell polarization.’ There are two cell polarization therapy strategies. The first involves inducing cells into a neuroprotective phenotype in vitro, then reintroducing them autologously. The second approach utilizes small molecular substances to directly affect cells in vivo. In this review, we elucidate the polarization dynamics of the three reactive cell populations(microglia, astrocytes, and neutrophils) in the context of ischemic stroke, and provide a comprehensive summary of the molecular mechanisms involved in their phenotypic switching. By unraveling the complexity of cell polarization, we hope to offer insights for future research on neuroinflammation and novel therapeutic strategies for ischemic stroke.展开更多
Background:LY01005(Goserelin acetate sustained-release microsphere injection)is a modified gonadotropin-releasing hormone(GnRH)agonist injected monthly.This phase III trial study aimed to evaluated the efficacy and sa...Background:LY01005(Goserelin acetate sustained-release microsphere injection)is a modified gonadotropin-releasing hormone(GnRH)agonist injected monthly.This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer.Methods:We conducted a randomized controlled,open-label,non-inferiority trial across 49 sites in China.This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections.The primary efficacy endpoints were the percentage of patients with testosterone suppression≤50 ng/dL at day 29 and the cumulative probability of testosterone≤50 ng/dL from day 29 to 85.Non-inferiority was prespecified at a margin of-10%.Secondary endpoints included significant castration(≤20 ng/dL),testosterone surge within 72 h following repeated dosing,and changes in luteinizing hormone,follicle-stimulating hormone,and prostate specific antigen levels.Results:On day 29,in the LY01005 and goserelin implant groups,testosterone concentrations fell below medical-castration levels in 99.3%(142/143)and 100%(140/140)of patients,respectively,with a difference of-0.7%(95%confidence interval[CI],-3.9%to 2.0%)between the two groups.The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3%and 97.8%,respectively,with a between-group difference of 1.5%(95%CI,-1.3%to 4.4%).Both results met the criterion for non-inferiority.Secondary endpoints were similar between groups.Both treatments were well-tolerated.LY01005 was associated with fewer injection-site reactions than the goserelin implant(0%vs.1.4%[2/145]).Conclusion:LY01005 is as effective as goserelin implants in reducing testosterone to castration levels,with a similar safety profile.Trial registration:ClinicalTrials.gov,NCT04563936.展开更多
Yttrium is a main kind of rare earth elements（REEs） with wide applications in modern industry and farming. Phosphorus, an essential element of algae, is used as the nutrients and also one of the main factors of eutr...Yttrium is a main kind of rare earth elements（REEs） with wide applications in modern industry and farming. Phosphorus, an essential element of algae, is used as the nutrients and also one of the main factors of eutrophication. To investigate the effects of yttrium and phosphorus on Microcystis aeruginosa（M. aeruginosa）, the growth and physiological changes were studied by lab cultured experiments. In the experiment, exogenous yttrium was tested by a concentration gradient（0.0, 0.1, 0.3, 0.5, 1.0 mg/L）,meanwhile, phosphorus was tested by three concentrations（0.0, 0.02, 0.2 mg/L）. The results show that the contents of chlorophyll a（chl-a） and soluble protein increase compared with the control and they have certain correlation with algal cells density. The growth status of algae is stimulated by initial yttrium concentration 〈0.3 and 0.2 mg/L phosphorus, while it is inhabited by 0.5 and 1.0 mg/L yttrium. Besides,the activity of superoxide dismutase（SOD） of algae increases with addition of yttrium dose（0-0.3 mg/L）when phosphorus dose is 0.2 mg/L. Furthermore, when yttrium dose is 0.5 and 1.0 mg/L, the vitality of SOD presents a sharp decline. The malondialdehyde（MDA） contents increase with time and addition of yttrium dose, 0.2 mg/L phosphorus weakens the accumulation of MDA.展开更多
基金supported by the National Natural Science Foundation of China, Nos.82201474 (to GL), 82071330 (to ZT), and 92148206 (to ZT)Key Research and Discovery Program of Hubei Province, No.2021BCA109 (to ZT)。
文摘Ischemic stroke is a cerebrovascular disease associated with high mortality and disability rates. Since the inflammation and immune response play a central role in driving ischemic damage, it becomes essential to modulate excessive inflammatory reactions to promote cell survival and facilitate tissue repair around the injury site. Various cell types are involved in the inflammatory response, including microglia, astrocytes, and neutrophils, each exhibiting distinct phenotypic profiles upon stimulation. They display either proinflammatory or anti-inflammatory states, a phenomenon known as ‘cell polarization.’ There are two cell polarization therapy strategies. The first involves inducing cells into a neuroprotective phenotype in vitro, then reintroducing them autologously. The second approach utilizes small molecular substances to directly affect cells in vivo. In this review, we elucidate the polarization dynamics of the three reactive cell populations(microglia, astrocytes, and neutrophils) in the context of ischemic stroke, and provide a comprehensive summary of the molecular mechanisms involved in their phenotypic switching. By unraveling the complexity of cell polarization, we hope to offer insights for future research on neuroinflammation and novel therapeutic strategies for ischemic stroke.
文摘Background:LY01005(Goserelin acetate sustained-release microsphere injection)is a modified gonadotropin-releasing hormone(GnRH)agonist injected monthly.This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer.Methods:We conducted a randomized controlled,open-label,non-inferiority trial across 49 sites in China.This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections.The primary efficacy endpoints were the percentage of patients with testosterone suppression≤50 ng/dL at day 29 and the cumulative probability of testosterone≤50 ng/dL from day 29 to 85.Non-inferiority was prespecified at a margin of-10%.Secondary endpoints included significant castration(≤20 ng/dL),testosterone surge within 72 h following repeated dosing,and changes in luteinizing hormone,follicle-stimulating hormone,and prostate specific antigen levels.Results:On day 29,in the LY01005 and goserelin implant groups,testosterone concentrations fell below medical-castration levels in 99.3%(142/143)and 100%(140/140)of patients,respectively,with a difference of-0.7%(95%confidence interval[CI],-3.9%to 2.0%)between the two groups.The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3%and 97.8%,respectively,with a between-group difference of 1.5%(95%CI,-1.3%to 4.4%).Both results met the criterion for non-inferiority.Secondary endpoints were similar between groups.Both treatments were well-tolerated.LY01005 was associated with fewer injection-site reactions than the goserelin implant(0%vs.1.4%[2/145]).Conclusion:LY01005 is as effective as goserelin implants in reducing testosterone to castration levels,with a similar safety profile.Trial registration:ClinicalTrials.gov,NCT04563936.
文摘Yttrium is a main kind of rare earth elements（REEs） with wide applications in modern industry and farming. Phosphorus, an essential element of algae, is used as the nutrients and also one of the main factors of eutrophication. To investigate the effects of yttrium and phosphorus on Microcystis aeruginosa（M. aeruginosa）, the growth and physiological changes were studied by lab cultured experiments. In the experiment, exogenous yttrium was tested by a concentration gradient（0.0, 0.1, 0.3, 0.5, 1.0 mg/L）,meanwhile, phosphorus was tested by three concentrations（0.0, 0.02, 0.2 mg/L）. The results show that the contents of chlorophyll a（chl-a） and soluble protein increase compared with the control and they have certain correlation with algal cells density. The growth status of algae is stimulated by initial yttrium concentration 〈0.3 and 0.2 mg/L phosphorus, while it is inhabited by 0.5 and 1.0 mg/L yttrium. Besides,the activity of superoxide dismutase（SOD） of algae increases with addition of yttrium dose（0-0.3 mg/L）when phosphorus dose is 0.2 mg/L. Furthermore, when yttrium dose is 0.5 and 1.0 mg/L, the vitality of SOD presents a sharp decline. The malondialdehyde（MDA） contents increase with time and addition of yttrium dose, 0.2 mg/L phosphorus weakens the accumulation of MDA.
