Selecting the initial antipsychotic dose is a high-impact decision in acute schizophrenia.A randomized study found that starting lurasidone at 80 mg/day for 1 week(then flexible titration)produced earlier reductions i...Selecting the initial antipsychotic dose is a high-impact decision in acute schizophrenia.A randomized study found that starting lurasidone at 80 mg/day for 1 week(then flexible titration)produced earlier reductions in Positive and Negative Syndrome Scale positive symptoms than 40 mg/day,without higher discontinuations for adverse events or a metabolic penalty over 6 weeks.These data support an individualized approach:Start at 80 mg/day when rapid control of positive symptoms or agitation is needed and tolerance permits;start at 40 mg/day when akathisia risk or patient preference argues for caution,with a planned day-7 review for up-titration.The open-label design,dose convergence after week 1,and the lack of stratified randomization limit attribution of longer-term advantages to starting dose.Even so,the trial reframes initial dose as a modifiable lever for the early course rather than a one-size-fits-all rule and warrants confirmation in larger,double-blind randomized trials.展开更多
Waste glass fibers were used as the main raw materials to prepare foamed glass-ceramics with 0-14 wt%H_(3)BO_(3)as a flux agent.The effects of H_(3)BO_(3)on the crystallization process,foaming behavior,and physical pr...Waste glass fibers were used as the main raw materials to prepare foamed glass-ceramics with 0-14 wt%H_(3)BO_(3)as a flux agent.The effects of H_(3)BO_(3)on the crystallization process,foaming behavior,and physical properties of CaO-MgO-Al_(2)O_(3)-SiO_(2)foamed glass-ceramics were investigated.The results showed that the main crystalline phase of the foamed glass-ceramics was anorthite with diopside as a minor crystalline phase,which exhibited a typical surface crystallization process.The addition of H_(3)BO_(3)modified the surface of glass powders and inhibited crystal precipitation obviously.The low melting point of H_(3)BO_(3)and the decrease of crystallinity jointly promoted the growth of pores,resulting in a reduction of bulk density and an increase in porosity.The compressive strength and thermal conductivity of the samples were linearly related to the bulk density.In particular,the sample added with 10 wt%H_(3)BO_(3)exhibited excellent properties,possessing a low coefficient of thermal conductivity 0.081 W/(m·K)and relatively high compressive strength 3.36 MPa.展开更多
Objective:To study the potential of Pituranthos chloranthus essential oil(PC)as a chemoprotective agent.Methods:In the in vitro study,cell proliferation were determined in CT26,SW620,and SW480 cells.Cells were exposed...Objective:To study the potential of Pituranthos chloranthus essential oil(PC)as a chemoprotective agent.Methods:In the in vitro study,cell proliferation were determined in CT26,SW620,and SW480 cells.Cells were exposed to in creasing concentrations of PC(0,6.25,12.5,25,50,100,and 200μg/mL).Combination index was calculated by applying the Chou-Talalay method,apoptopsis was analyzed by annexin V/propidium iodide staining,reactive oxygen species accumulation,and theΔψm drop were also assessed.In the in vivo study,mice were divided into 5 groups:the normal control group,the CT26 tumor-bearing group,the CT26 tumor-bearing mice+PC group,the CT26 tumor-bearing mice+cisplatin group,and the CT26 tumor-bearing mice+cisplatin+PC group.Organ coefficients and tumor volume were calculated.Alanine aminotransferase,aspartate aminotransferase,creatinine,and tumor necrosis factor-αlevels were assessed.Results:Cisplatin with PC induced a synergistic effect,allowing for reduced cisplatin dose while maintaining the same therapeutic efficacy.PC-cisplatin combinations inhibited cell viability by significantly inducing apoptosis,increasing reactive oxygen species accumulation and reducing mitochondrial membrane potential.Co-treatment with cisplatin and PC restored organ coefficients,reduced tumor volume,and alleviated nephrotoxicity in CT26 tumor-bearing mice by restoring kidney function markers and ameliorating kidney inflammation status.Conclusions:PC shows a chemoprotective potential by enhancing the antitumor effect of cisplatin while alleviating its side effects.展开更多
BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithel...BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithelial cells has a causal role leading to infiltration of neutrophils into the colonic mucosa and subsequent development of UC.This evidence-based mechanism identifies hydrogen peroxide as a therapeutic target for reducing agents in the treatment of UC.CASE SUMMARY Presented is a 41-year-old female with a 26-year history of refractory UC.Having developed steroid dependence and never achieving complete remission on treatment by conventional and advanced therapies,she began treatment with oral R-dihydrolipoic acid(RDLA),a lipid-soluble reducing agent with intracellular site of action.Within a week,rectal bleeding ceased.She was asymptomatic for three years until a highly stressful experience,when she noticed blood in her stool.RDLA was discontinued,and she began treatment with oral sodium thiosulfate pentahydrate(STS),a reducing agent with extracellular site of action.After a week,rectal bleeding ceased,and she resumed oral RDLA and discontinued STS.To date,she remains asymptomatic with normal stool calprotectin while on RDLA.CONCLUSION STS and RDLA are reducing agents that serve as highly effective and safe therapy for the induction and maintenance of remission in UC,even in patients refractory or poorly controlled by conventional and advanced therapies.Should preliminary findings be validated by subsequent clinical trials,the use of reducing agents could potentially prevent thousands of colectomies and represent a paradigm shift in the treatment of UC.展开更多
Owing to the emergence of drug resistance and high morbidity,the need for novel antiviral drugs with novel targets is highly sought after.Marine-derived compounds mostly possess potent antiviral activity and serve as ...Owing to the emergence of drug resistance and high morbidity,the need for novel antiviral drugs with novel targets is highly sought after.Marine-derived compounds mostly possess potent antiviral activity and serve as a primary source for developing novel antiviral drugs,making the rapid discovery and evaluation of marine antiviral agents particularly crucial.Thus,future research should place greater emphasis on the identification of novel antiviral targets through the combination of artificial intelligence(AI)and structural pharmacology,as well as expanding the marine resource and target databases.展开更多
针对体系优化存在的体系建模困难、难以量化反映体系效能问题,本文在深入分析武器装备体系结构基础上,通过基于Agent的建模和图示评审技术(graphical evaluation and review technique,GERT)构建具有自学习机制的体系A-GERT网络,实现体...针对体系优化存在的体系建模困难、难以量化反映体系效能问题,本文在深入分析武器装备体系结构基础上,通过基于Agent的建模和图示评审技术(graphical evaluation and review technique,GERT)构建具有自学习机制的体系A-GERT网络,实现体系效能优化。其次,基于矩母函数与梅森公式给出了体系作战链/网任务成功概率和作战效能的计算方法和证明,并在深刻剖析体系组成单元贡献的基础上,借助合作博弈的利益公平分配思想,提出了基于Shapley值的体系组成单元期望贡献评估模型。然后,基于马尔可夫过程理论,提出了基于组成单元贡献的A-GERT网络体系效能优化算法。最后结合实例研究,说明了所提模型的可行性和有效性。展开更多
文摘Selecting the initial antipsychotic dose is a high-impact decision in acute schizophrenia.A randomized study found that starting lurasidone at 80 mg/day for 1 week(then flexible titration)produced earlier reductions in Positive and Negative Syndrome Scale positive symptoms than 40 mg/day,without higher discontinuations for adverse events or a metabolic penalty over 6 weeks.These data support an individualized approach:Start at 80 mg/day when rapid control of positive symptoms or agitation is needed and tolerance permits;start at 40 mg/day when akathisia risk or patient preference argues for caution,with a planned day-7 review for up-titration.The open-label design,dose convergence after week 1,and the lack of stratified randomization limit attribution of longer-term advantages to starting dose.Even so,the trial reframes initial dose as a modifiable lever for the early course rather than a one-size-fits-all rule and warrants confirmation in larger,double-blind randomized trials.
基金Funded by Shandong Provincial Youth Innovation Team Development Plan of Colleges and Universities(No.2022KJ100)National Natural Science Foundation of China(No.52172019)。
文摘Waste glass fibers were used as the main raw materials to prepare foamed glass-ceramics with 0-14 wt%H_(3)BO_(3)as a flux agent.The effects of H_(3)BO_(3)on the crystallization process,foaming behavior,and physical properties of CaO-MgO-Al_(2)O_(3)-SiO_(2)foamed glass-ceramics were investigated.The results showed that the main crystalline phase of the foamed glass-ceramics was anorthite with diopside as a minor crystalline phase,which exhibited a typical surface crystallization process.The addition of H_(3)BO_(3)modified the surface of glass powders and inhibited crystal precipitation obviously.The low melting point of H_(3)BO_(3)and the decrease of crystallinity jointly promoted the growth of pores,resulting in a reduction of bulk density and an increase in porosity.The compressive strength and thermal conductivity of the samples were linearly related to the bulk density.In particular,the sample added with 10 wt%H_(3)BO_(3)exhibited excellent properties,possessing a low coefficient of thermal conductivity 0.081 W/(m·K)and relatively high compressive strength 3.36 MPa.
基金funded by The Tunisian Ministry of Research and Higher Education.
文摘Objective:To study the potential of Pituranthos chloranthus essential oil(PC)as a chemoprotective agent.Methods:In the in vitro study,cell proliferation were determined in CT26,SW620,and SW480 cells.Cells were exposed to in creasing concentrations of PC(0,6.25,12.5,25,50,100,and 200μg/mL).Combination index was calculated by applying the Chou-Talalay method,apoptopsis was analyzed by annexin V/propidium iodide staining,reactive oxygen species accumulation,and theΔψm drop were also assessed.In the in vivo study,mice were divided into 5 groups:the normal control group,the CT26 tumor-bearing group,the CT26 tumor-bearing mice+PC group,the CT26 tumor-bearing mice+cisplatin group,and the CT26 tumor-bearing mice+cisplatin+PC group.Organ coefficients and tumor volume were calculated.Alanine aminotransferase,aspartate aminotransferase,creatinine,and tumor necrosis factor-αlevels were assessed.Results:Cisplatin with PC induced a synergistic effect,allowing for reduced cisplatin dose while maintaining the same therapeutic efficacy.PC-cisplatin combinations inhibited cell viability by significantly inducing apoptosis,increasing reactive oxygen species accumulation and reducing mitochondrial membrane potential.Co-treatment with cisplatin and PC restored organ coefficients,reduced tumor volume,and alleviated nephrotoxicity in CT26 tumor-bearing mice by restoring kidney function markers and ameliorating kidney inflammation status.Conclusions:PC shows a chemoprotective potential by enhancing the antitumor effect of cisplatin while alleviating its side effects.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithelial cells has a causal role leading to infiltration of neutrophils into the colonic mucosa and subsequent development of UC.This evidence-based mechanism identifies hydrogen peroxide as a therapeutic target for reducing agents in the treatment of UC.CASE SUMMARY Presented is a 41-year-old female with a 26-year history of refractory UC.Having developed steroid dependence and never achieving complete remission on treatment by conventional and advanced therapies,she began treatment with oral R-dihydrolipoic acid(RDLA),a lipid-soluble reducing agent with intracellular site of action.Within a week,rectal bleeding ceased.She was asymptomatic for three years until a highly stressful experience,when she noticed blood in her stool.RDLA was discontinued,and she began treatment with oral sodium thiosulfate pentahydrate(STS),a reducing agent with extracellular site of action.After a week,rectal bleeding ceased,and she resumed oral RDLA and discontinued STS.To date,she remains asymptomatic with normal stool calprotectin while on RDLA.CONCLUSION STS and RDLA are reducing agents that serve as highly effective and safe therapy for the induction and maintenance of remission in UC,even in patients refractory or poorly controlled by conventional and advanced therapies.Should preliminary findings be validated by subsequent clinical trials,the use of reducing agents could potentially prevent thousands of colectomies and represent a paradigm shift in the treatment of UC.
文摘Owing to the emergence of drug resistance and high morbidity,the need for novel antiviral drugs with novel targets is highly sought after.Marine-derived compounds mostly possess potent antiviral activity and serve as a primary source for developing novel antiviral drugs,making the rapid discovery and evaluation of marine antiviral agents particularly crucial.Thus,future research should place greater emphasis on the identification of novel antiviral targets through the combination of artificial intelligence(AI)and structural pharmacology,as well as expanding the marine resource and target databases.
文摘针对体系优化存在的体系建模困难、难以量化反映体系效能问题,本文在深入分析武器装备体系结构基础上,通过基于Agent的建模和图示评审技术(graphical evaluation and review technique,GERT)构建具有自学习机制的体系A-GERT网络,实现体系效能优化。其次,基于矩母函数与梅森公式给出了体系作战链/网任务成功概率和作战效能的计算方法和证明,并在深刻剖析体系组成单元贡献的基础上,借助合作博弈的利益公平分配思想,提出了基于Shapley值的体系组成单元期望贡献评估模型。然后,基于马尔可夫过程理论,提出了基于组成单元贡献的A-GERT网络体系效能优化算法。最后结合实例研究,说明了所提模型的可行性和有效性。
