Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

Ferroptosis is a programmed cell death depends on iron and lipid peroxidation,which has been recognized as the key pathogenic factor for the occurrence of various diseases in recent years,especially playing a significant role in neurodegenerative diseases.Ferroptosis triggers lipid peroxidation and oxidative stress in neuronal cells,leading to neuronal damage and death,thereby accelerating disease progression.Hydrogen sulfide,as an endogenous gaseous signaling molecule,exhibits multiple protective effects,including anti-inflammatory,antioxidant,and anti-ferroptosis properties.Hydrogen sulfide can effectively inhibit the occurrence of ferroptosis through various mechanisms,such as regulating iron metabolism,inhibiting lipid peroxidation,and enhancing the activity of antioxidant enzymes,thereby slowing down the progression of neurodegenerative diseases.This article reviews the related research progress on hydrogen sulfide and ferroptosis and ferroptosis-mediated neurodegenerative diseases,and analyzes the underlying mechanisms,aims to provide new insights and theoretical foundations for the treatment of neurodegenerative diseases.

Aim To investigate the regulatory mecha-nisms of donepezil on the expression and enzymatic ac-tivity of cytochrome P450 3A4(CYP3A4),elucidate the synergistic impact of hypoxia on CYP3A4 function,and reveal its potential association with drug-induced cardiotoxicity,particularly QT interval prolongation.Methods Western blot,co-immunoprecipitation,and gene knockdown techniques were employed to evaluate the effects of donepezil and hypoxia on CYP3A4 pro-tein expression.CYP3A4 enzymatic activity was as-sessed using an in vitro incubation system with rat liver microsomes combined with high-performance liquid chromatography(HPLC),and the half-maximal inhib-itory concentration(IC50)was determined.Results Donepezil(10 μmol·L-1)and hypoxia reduced CYP3A4 protein expression to 31.75％and 45.90％of the control levels,respectively.Both interventions activated the gp78-mediated ubiquitin-proteasome path-way,significantly increasing CYP3A4 ubiquitination levels by 2.1-fold compared to the control group,thereby promoting proteasomal degradation.Donepezil inhibited CYP3A4 enzyme activity with an IC50 of 83.4μmol·L-1,and hypoxia synergistically enhanced this inhibitory effect,reducing the IC50 to 20.79 μmol·L-1.Conclusion Donepezil downregulates CYP3A4 function through dual mechanisms involving ubiquitin-mediated proteasomal degradation and direct enzymatic inhibition.Hypoxia potentiates this effect,leading to impaired metabolism of CYP3A4 substrate drugs,ele-vated plasma drug concentrations(1.6-2.3-fold in-crease compared to normal metabolic conditions),and an increased risk of QT interval prolongation and other forms of cardiotoxicity.

Under the new situation of establishing the new standard system for pharmaceutical packaging materials in the 2025 edition of the Chinese Pharmacopoeia and promulgating the appendix on pharmaceutical packaging ma-terials in the Good Manufacturing Practice for Drugs,it is urgently necessary to introduce relevant standards for quality agreements on pharmaceutical packaging materials.This article focuses on analyzing the development of group standards for pharmaceutical packaging materials under the new situation,the role and significance of quality agreements for pharmaceutical packaging materials,as well as the interpretation of key parts of the"Guidelines for the Management of Quality Agreements for Pharmaceutical Packaging Materials",in order to help enterprises quick-ly shift from the original"standard-only"approach to strengthening the quality management of the entire product life cycle through quality agreements.

Sacubitril valsartan sodium tablets are a novel supramolecular co-crystal drug that combines the dual effects of angiotensin receptor blockade and neprilysin inhibitor.It has shown broad application prospects in heart failure,hypertension,maintaining water sodium balance in the body,and protecting target organs,etc.It is a major breakthrough in cardiovascular treatment drugs in recent years.It is clinically used in China for chronic heart failure in adult patients with reduced ejection fraction and primary hypertension.In recent years,pharmaceutical co-crystals has become a hot topic in the research of crystalline drugs,and sacubitril valsartan sodium tablets,as a marketed co-crystal drug,have attracted industry attention.This article summarizes the characteristics of sacubitril valsartan sodium co-crystal drug,the application and approval cases through relevant literature investigation,and discussses pharmaceutical research of the formulation,in order to provide some references for the research and development of generic drugs.

Ferroptosis is a programmed cell death depends on iron and lipid peroxidation,which has been recognized as the key pathogenic factor for the occurrence of various diseases in recent years,especially playing a significant role in neurodegenerative diseases.Ferroptosis triggers lipid peroxidation and oxidative stress in neuronal cells,leading to neuronal damage and death,thereby accelerating disease progression.Hydrogen sulfide,as an endogenous gaseous signaling molecule,exhibits multiple protective effects,including anti-inflammatory,antioxidant,and anti-ferroptosis properties.Hydrogen sulfide can effectively inhibit the occurrence of ferroptosis through various mechanisms,such as regulating iron metabolism,inhibiting lipid peroxidation,and enhancing the activity of antioxidant enzymes,thereby slowing down the progression of neurodegenerative diseases.This article reviews the related research progress on hydrogen sulfide and ferroptosis and ferroptosis-mediated neurodegenerative diseases,and analyzes the underlying mechanisms,aims to provide new insights and theoretical foundations for the treatment of neurodegenerative diseases.

Objective To investigate the effects of long non-coding RNA FGD5-AS1 on the proliferation,migration,and invasion of pituitary adenoma(PA)cells,and to analyze its potential mechanism of action.Methods Human PA cell lines HPAs,RC-4BC,HP75,and human astrocyte cell line NHA were cultured in vitro.The expression levels of FGD5-AS1 and miR-15a in the above cell lines were detected by RT-PCR.HP75 cells in the logarithmic growth phase were randomly divided into the silencing group and the negative control group.The silencing group was transfected with shRNA-FGD5-AS1,while the negative control group was transfected with shRNA-NC.The expression levels of FGD5-AS1 and miR-15a in the two groups of cells were detected by RT-PCR.The proliferation,migration and invasion abilities of the two groups of cells were determined by CCK-8 assay,wound healing assay,and Transwell assay.The expression of proteins related to the Wnt/β-catenin signaling pathway in the two groups of cells was detected by Western blot.The targeting relationship between FGD5-AS1 and miR-15a was verified by dual-luciferase reporter gene assay.Results Compared with the NHA cell,the expression level of FGD5-AS1 was significantly increased in the HPAs,RC-4BC,and HP75 cells((P<0.05),whereas the expression level of miR-15a was significantly decreased(P<0.05).Compared with the negative control group,the expression level of FGD5-AS1 was decreased(P<0.05),the expression level of miR-15a was increased(P<0.05),the OD value was decreased(P<0.05),the migration and invasion abilities of cells were reduced(P<0.05),and the expression of Wnt3a and β-catenin proteins was decreased in the silencing group of HP75 cells(P<0.05).FGD5-AS1 could specifically bind to miR-15a,leading to a decrease in cell luciferase activity(P<0.05).Conclusion FGD5-AS1 is overexpressed in PA cells,and silencing FGD5-AS1 can inhibit the proliferation,migration,and invasion of PA cells,and the mechanism is related to its targeted regulation of miR-15a.

Aim To investigate the regulatory mecha-nisms of donepezil on the expression and enzymatic ac-tivity of cytochrome P450 3A4(CYP3A4),elucidate the synergistic impact of hypoxia on CYP3A4 function,and reveal its potential association with drug-induced cardiotoxicity,particularly QT interval prolongation.Methods Western blot,co-immunoprecipitation,and gene knockdown techniques were employed to evaluate the effects of donepezil and hypoxia on CYP3A4 pro-tein expression.CYP3A4 enzymatic activity was as-sessed using an in vitro incubation system with rat liver microsomes combined with high-performance liquid chromatography(HPLC),and the half-maximal inhib-itory concentration(IC50)was determined.Results Donepezil(10 μmol·L-1)and hypoxia reduced CYP3A4 protein expression to 31.75％and 45.90％of the control levels,respectively.Both interventions activated the gp78-mediated ubiquitin-proteasome path-way,significantly increasing CYP3A4 ubiquitination levels by 2.1-fold compared to the control group,thereby promoting proteasomal degradation.Donepezil inhibited CYP3A4 enzyme activity with an IC50 of 83.4μmol·L-1,and hypoxia synergistically enhanced this inhibitory effect,reducing the IC50 to 20.79 μmol·L-1.Conclusion Donepezil downregulates CYP3A4 function through dual mechanisms involving ubiquitin-mediated proteasomal degradation and direct enzymatic inhibition.Hypoxia potentiates this effect,leading to impaired metabolism of CYP3A4 substrate drugs,ele-vated plasma drug concentrations(1.6-2.3-fold in-crease compared to normal metabolic conditions),and an increased risk of QT interval prolongation and other forms of cardiotoxicity.

Under the new situation of establishing the new standard system for pharmaceutical packaging materials in the 2025 edition of the Chinese Pharmacopoeia and promulgating the appendix on pharmaceutical packaging ma-terials in the Good Manufacturing Practice for Drugs,it is urgently necessary to introduce relevant standards for quality agreements on pharmaceutical packaging materials.This article focuses on analyzing the development of group standards for pharmaceutical packaging materials under the new situation,the role and significance of quality agreements for pharmaceutical packaging materials,as well as the interpretation of key parts of the"Guidelines for the Management of Quality Agreements for Pharmaceutical Packaging Materials",in order to help enterprises quick-ly shift from the original"standard-only"approach to strengthening the quality management of the entire product life cycle through quality agreements.

Core competitiveness of medical colleges and universities refers to their unique advantages and abilities in teaching,research and serving society compared to other colleges.As an important part of core competitiveness of medical colleges,teachers'teaching ability directly affects students'learning effect and quality training,and also relates to overall promotion process of core com-petitiveness of medical colleges.From perspective of core competitiveness of medical colleges,this paper analyzes and combs develop-ment of teachers'teaching ability from theoretical definition of core competitiveness of medical colleges,finds bottleneck of improving teachers'teaching ability,and puts forward suggestions for improving teachers'teaching ability in medical colleges,so as to improve teachers'teaching ability in medical colleges.