Ischemic stroke (IS) ranks as a leading cause of death and disability globally. The blood-brain barrier (BBB) poses significant challenges for effective drug delivery to brain tissues. Recent decades have seen the development of targeted nanomedicine and biomimetic technologies, sparking substantial interest in biomimetic drug delivery systems for treating IS. These systems are devised by utilizing or replicating natural cells and their derivatives, offering promising new pathways for detection and transport across the BBB. Their multifunctionality and high biocompatibility make them effective treatment options for IS. In addition, the incorporation of engineering techniques has provided these biomimetic drug delivery systems with active targeting capabilities, enhancing the accumulation of therapeutic agents in ischemic tissues and specific cell types. This improvement boosts drug transport and therapeutic efficacy. However, it is crucial to thoroughly understand the advantages and limitations of various engineering strategies employed in constructing biomimetic delivery systems. Selecting appropriate construction methods based on the characteristics of the disease is vital to achieving optimal treatment outcomes. This review summarizes recent advancements in three types of engineered biomimetic drug delivery systems, developed from natural cells and their derivatives, for treating IS. It also discusses their effectiveness in application and potential challenges in future clinical translation.
Humans ; Drug Delivery Systems/methods* ; Ischemic Stroke/drug therapy* ; Animals ; Blood-Brain Barrier/metabolism* ; Stroke/drug therapy*

AIM:To investigate the protective mechanism of calycosin(CA)on renal structure and antioxi-dant capacity in acute kidney injury(AKI)mice.METHODS:Thirty male C57BL/6J mice were allocated into control group,model group,and treatment group.The treatment group was further subdivided into low-dose CA,middle-dose CA,and high-dose CA groups,receiving 5 mg/kg,10 mg/kg,and 20 mg/kg CA solution by gavage for 6 days.After the pre-treatment phase,both the model and treatment groups were administered an intraperitoneal injection of 20 mg/kg of cis-platin(CDDP)to induce AKI modeling.Specimens from the mice were collected 72 hours post-modeling for further analy-sis.The body weight and the mean mass of both kidneys were assessed.Serum creatinine(SCr)and blood urea nitrogen(BUN)levels were assessed to evaluate kidney function.Kidney pathology was assessed with periodic acid-Schiff(PAS)staining,while protein levels of superoxide dismutase 1(SOD1),SOD2,glutathione peroxidase 1(GPX1),and catalase were evaluated using Western blot and immunohistochemistry assay.RESULTS:Compared with the control group,the model group exhibited a substantial reduction in body mass,a significant increase in the mean mass of bilateral kidneys,and elevated levels of SCr and BUN,indicating impaired renal function(P<0.01).PAS staining revealed pronounced structural damage to the glomeruli and renal tubules,with widespread appearance of tubular casts in model group.The re-sults of Western blot and immunohistochemical staining demonstrated significantly reduced expression of antioxidant en-zymes SOD1,SOD2,GPX1,and catalase(P<0.05).The body weight of mice in the low-dose and middle-dose CA groups exhibited a significant increase than those in the model group,and the kidney weights of mice in Low-dose,middle-dose,and high-dose CA groups were significantly lower than those of mice in the model group(P<0.05).Additionally,SCr and BUN levels were significantly reduced(P<0.01).PAS staining indicated obvious recovery of glomeruli and renal tubules after CA treatment.SOD1 and GPX1 levels were elevated in the middle-dose and high-dose CA groups,and SOD2 and catalase levels were significantly higher in the middle-dose CA group(P<0.05),compared with model group.CON-CLUSION:CA can alleviate CDDP-induced kidney injury in AKI mice by enhancing the expression of antioxidant enzymes SOD1,SOD2,GPX1,and catalase.

Objective To explore the influencing factors of cognitive impairment in non-dialysis patients with chronic kidney disease(CKD).Methods A total of 60 hospitalized non-dialysis patients with CKD in the Department of Nephrology of Northern Jiangsu People's Hospital Affiliated to Yangzhou University from September 2022 to September 2023 were enrolled as research objects.According to the estimated glomerular filtration rate(eGFR),they were divided into stage 1 to 2 of CKD group[eGFR ≥60 mL/(min·1.73 m2)]with 23 cases,the stage 3 of CKD group[eGFR 30～＜60 mL/(min·1.73 m2)]with 20 cases,and stage 4 to 5 of CKD group[eGFR＜30 mL/(min·1.73 m2)]with 17 cases.The Montreal Cognitive Assessment Scale(MoCA)was used to evaluate the cognitive function of the patients.Basic data and common clinical laboratory in-dicators on hospital admission were collected to analyze the differences in cognitive function levels under different renal function statuses and to explore the influencing factors of cognitive impairment.Results The incidence rates of cognitive impairment in the stage 1 to 2 of CKD group,stage 3 of CKD group,and stage 4 to 5 of CKD group were 47.8％,85.0％,and 94.1％respectively,the median MoCA scored 26,24 and 20 respectively,with statistically significant between-group differ-ences(P＜0.05).Cognitive function was significantly negatively correlated with age(r=-0.634,P＜0.001),blood urea nitrogen(BUN)(r=-0.574,P＜0.001),serum creatinine(Cr)(r=-0.417,P＜0.001),cystatin C(Cys-C)(r=-0.327,P=0.011),serum β2-microglobulin(β2-MG)(r=-0.259,P=0.046),and N-terminal pro-brain natriuretic peptide(NT-proBNP)(r=-0.474,P＜0.001),and was significantly positively correlated with hemoglobin(HB)(r=0.401,P=0.001)and eGFR(r=0.485,P＜0.001).Multivariate Logistic regression analysis showed that age(P=0.006)and NT-proBNP(P=0.041)were influencing factors of cognitive im-pairment in non-dialysis patients with CKD.Receiver operating characteristic(ROC)curve analysis showed that the area under the curve(AUC),sensitivity,and specificity of age for prediction were 0.860,0.864 and 0.812 respectively,the AUC,sensitivity,and specificity of NT-proBNP for pre-diction were 0.808,0.795 and 0.875 respectively,and the combined prediction of age and NT-proBNP had an AUC,sensitivity,and specificity of 0.893,0.955,and 0.750,respectively.Conclusion As renal function deteriorates,the incidence rate and severity of cognitive impairment in non-dialysis patients with CKD tend to increase.Advanced age,renal function deterioration,high NT-proBNP level,and anemia are associated with the occurrence of cognitive impairment in non-di-alysis patients with CKD,among which age and NT-proBNP are influencing factors for cognitive im-pairment.

Objective To investigate the biomechanical characteristics of clear aligners combined with Class Ⅱelastics during retraction of upper anterior teeth,and compare the differences between two traction methods.Methods A case with a molar distal relationship and extraction of four first premolars was selected.The finite element method was applied to analyze tooth displacement,force distribution,and periodontal ligament(PDL)stress during 0.2 mm en-masse retraction of the anterior teeth.Three working conditions were defined:en-masse retraction without elastics(Condition 1),120 g Class Ⅱ elastics with aligner-cut hooks on upper canines and lower first molars(Condition 2),120 g Class Ⅱ elastics with aligner windows and bonded buttons on upper canines and lower first molars(Condition 3).Results Class Ⅱ elastics significantly enhanced lingual movement of the upper anterior teeth and mesial movement of the lower posterior teeth,while reducing mesial movement of the upper posterior teeth and lingual movement of the lower anterior teeth.In the transverse direction,the forces exerted on the teeth in all three conditions were minimal.In the sagittal direction,in Condition 2,the mesial force of the upper posterior teeth was effectively reduced by an average of 0.13 N,and the mesial force of the lower posterior teeth was increased by an average of 0.31 N.In Condition 3,the distal force of the upper canine teeth and the mesial force of the lower first molar were significantly increased by 0.40 N and 1.14 N,respectively.In the vertical direction,In condition 2,the average extrusive force of the upper teeth and the extrusive force of the lower molars were increased by 0.22 N and 0.20 N,respectively.In Condition 3,the upper canine extrusive force was increased by 0.91 N,while the lower molar intrusive force and the second molar extrusive force were reduced by 0.27 N and 0.25 N,respectively.The PDL stress distribution in the three conditions was generally similar.In Condition 3,the maximum principal stress distribution area on the lower first molars expanded slightly,but the magnitude did not increase significantly.Conclusions Condition 2 optimized the lower posterior teeth mesialization through balanced force distribution and protected the upper posterior teeth anchorage.Condition 3 significantly increased extrusive and distal forces on the upper canines and mesial forces on the lower first molars but did not substantially elevate periodontal risks for these teeth.

Objective To investigate the biomechanical characteristics of clear aligners combined with Class Ⅱelastics during retraction of upper anterior teeth,and compare the differences between two traction methods.Methods A case with a molar distal relationship and extraction of four first premolars was selected.The finite element method was applied to analyze tooth displacement,force distribution,and periodontal ligament(PDL)stress during 0.2 mm en-masse retraction of the anterior teeth.Three working conditions were defined:en-masse retraction without elastics(Condition 1),120 g Class Ⅱ elastics with aligner-cut hooks on upper canines and lower first molars(Condition 2),120 g Class Ⅱ elastics with aligner windows and bonded buttons on upper canines and lower first molars(Condition 3).Results Class Ⅱ elastics significantly enhanced lingual movement of the upper anterior teeth and mesial movement of the lower posterior teeth,while reducing mesial movement of the upper posterior teeth and lingual movement of the lower anterior teeth.In the transverse direction,the forces exerted on the teeth in all three conditions were minimal.In the sagittal direction,in Condition 2,the mesial force of the upper posterior teeth was effectively reduced by an average of 0.13 N,and the mesial force of the lower posterior teeth was increased by an average of 0.31 N.In Condition 3,the distal force of the upper canine teeth and the mesial force of the lower first molar were significantly increased by 0.40 N and 1.14 N,respectively.In the vertical direction,In condition 2,the average extrusive force of the upper teeth and the extrusive force of the lower molars were increased by 0.22 N and 0.20 N,respectively.In Condition 3,the upper canine extrusive force was increased by 0.91 N,while the lower molar intrusive force and the second molar extrusive force were reduced by 0.27 N and 0.25 N,respectively.The PDL stress distribution in the three conditions was generally similar.In Condition 3,the maximum principal stress distribution area on the lower first molars expanded slightly,but the magnitude did not increase significantly.Conclusions Condition 2 optimized the lower posterior teeth mesialization through balanced force distribution and protected the upper posterior teeth anchorage.Condition 3 significantly increased extrusive and distal forces on the upper canines and mesial forces on the lower first molars but did not substantially elevate periodontal risks for these teeth.

AIM:To investigate the protective mechanism of calycosin(CA)on renal structure and antioxi-dant capacity in acute kidney injury(AKI)mice.METHODS:Thirty male C57BL/6J mice were allocated into control group,model group,and treatment group.The treatment group was further subdivided into low-dose CA,middle-dose CA,and high-dose CA groups,receiving 5 mg/kg,10 mg/kg,and 20 mg/kg CA solution by gavage for 6 days.After the pre-treatment phase,both the model and treatment groups were administered an intraperitoneal injection of 20 mg/kg of cis-platin(CDDP)to induce AKI modeling.Specimens from the mice were collected 72 hours post-modeling for further analy-sis.The body weight and the mean mass of both kidneys were assessed.Serum creatinine(SCr)and blood urea nitrogen(BUN)levels were assessed to evaluate kidney function.Kidney pathology was assessed with periodic acid-Schiff(PAS)staining,while protein levels of superoxide dismutase 1(SOD1),SOD2,glutathione peroxidase 1(GPX1),and catalase were evaluated using Western blot and immunohistochemistry assay.RESULTS:Compared with the control group,the model group exhibited a substantial reduction in body mass,a significant increase in the mean mass of bilateral kidneys,and elevated levels of SCr and BUN,indicating impaired renal function(P<0.01).PAS staining revealed pronounced structural damage to the glomeruli and renal tubules,with widespread appearance of tubular casts in model group.The re-sults of Western blot and immunohistochemical staining demonstrated significantly reduced expression of antioxidant en-zymes SOD1,SOD2,GPX1,and catalase(P<0.05).The body weight of mice in the low-dose and middle-dose CA groups exhibited a significant increase than those in the model group,and the kidney weights of mice in Low-dose,middle-dose,and high-dose CA groups were significantly lower than those of mice in the model group(P<0.05).Additionally,SCr and BUN levels were significantly reduced(P<0.01).PAS staining indicated obvious recovery of glomeruli and renal tubules after CA treatment.SOD1 and GPX1 levels were elevated in the middle-dose and high-dose CA groups,and SOD2 and catalase levels were significantly higher in the middle-dose CA group(P<0.05),compared with model group.CON-CLUSION:CA can alleviate CDDP-induced kidney injury in AKI mice by enhancing the expression of antioxidant enzymes SOD1,SOD2,GPX1,and catalase.

Objective:To develop an efficient and robust method based on three dimensional facial landmarks for evaluating chin region asymmetry at the soft tissue level and to compare it with the tradi-tional mirror-overlap analysis method in order to test its availability.Methods:Standard symmetrical face was used for mental tubercle coordinate transformation so as to filter soft tissue three dimensional spatial angle and construct corresponding three dimensional spatial angle wireframe template.Ten patients aged 12-32 years with clinical chin region asymmetry diagnosis at the Department of Orthodontics of Peking University Hospital of Stomatology from November 2020 to November 2021 were randomly selected.Three dimensional soft tissue face scan data of the patients were collected by three dimensional face scanner and the landmark points were automatically determined by the Meshmonk non-rigid registration algorithm pro-gram,and in this way,the asymmetric three dimensional spatial angle wireframe template and corre-sponding spatial angle parameters were generated.Mirror-overlap analysis of face scan data was also per-formed in Geomagic Studio 2015 software and deviation color maps were generated.This study took mirror-overlap analysis as the gold standard method,the response rate of chin region asymmetry was eva-luated by the outcomes of the mirror-overlap analysis and three dimensional spatial angle wireframe tem-plate analysis.Results:Nine three dimensional spatial angle indicators were selected through coordinate transformation,and the response rate was calculated using mirror-overlap analysis as the gold standard method.Among these ten selected patients,the response rate of the total chin region asymmetry was 90％(9/10).Using the deviation value of mirror-overlap analysis as a reference,the response rate of chin region asymmetry in the X dimension was 86％,the response rate of chin region asymmetry in the Y dimension was 89％,and the response rate of chin region asymmetry in the Z dimension was 100％.Conclusion:The three dimensional soft tissue spatial angle wireframe template proposed in this study has some feasibility in evaluating chin region asymmetry at the soft tissue level,and its ability to recognize asymmetry separately in the three dimensional direction is better than the mirror-overlap analysis method,and the indicators recognition rate still needs to be further improved.

In the field of dental aesthetics,digital aesthetic design plays a crucial role in helping dentists to predict treatment outcomes vis-ually,as well as in enhancing the consistency of knowledge and understanding of aesthetic goals between dentists and patients.It serves as the foundation for achieving ideal aesthetic effects.However,there is no clear standard for this digital process currently in China and abroad.Many dentists lack of systematic understanding of how to carry out digital aesthetic design for treatment.To establish standardized processes for dental aesthetic design and to improve the homogeneity of treatment outcomes,Chinese Society of Digital Dental Industry(CSD-DI)convened domestic experts in related field to compile this consensus.This article elaborates on the key aspects of digital aesthetic data collection,integration steps,and the digital aesthetic design process.It also formulates a decision tree for dental aesthetics at macro level and outlines corresponding workflows for various clinical scenarios,serving as a reference for clinicians.

Objective:To explore the digital design and fabrication technology of personalized restorative matrix for dental filling, and to explore the feasibility of direct resin restoration for deep caries lesions in distal neck of mandibular second molar.Methods:For patients with deep caries lesions in the distal neck of the mandibular second molar who visited the Department of Cariology and Endodontology of Peking University School and Hospital of Stomatology from September 2023 to April 2024, after preparing the cavity and gingival retractor, a three-dimensional intraoral scanner was used to obtain three-dimensional data of the patient′s dentition. In the dental restoration computer-aided design software, the inlay function was used to generate the restored tooth morphology. The edge range of the personalized restorative matrix was drawn on the restored model by three-dimensional reverse engineering software to achieve edge sealing effect. The selected edge range data was processed with distal shelling to generate a digital model of a personalized restorative matrix with a thickness of 0.5 mm. A metal three-dimensional printer was used to fabricate the titanium alloy restorative matrix, and its application was completed in 10 clinical cases. The marginal adaptation and retention stability of the personalized restorative matrix were evaluated under a dental microscope, and forming effect evaluation was performed through immediate postoperative periapical radiographs.Results:The preliminary clinical application of the personalized restorative matrix fabricated using digital technology revealed that, in the treatment of 10 affected teeth, rubber dam isolation was successfully ensured, resulting in clinically effective direct resin composite restorations with optimal marginal adaptation and reasonable contours. Immediate postoperative periapical radiographs showed good convexity of the filling body, with no overhangs found. Both marginal adaptation and retention stability met the requirements of clinical treatment.Conclusions:The personalized restorative matrix designed in this study can solve the clinical problems of moisture separation and resin forming in the treatment of deep caries lesions in distal neck of the mandibular second molar, and can achieve stable and reliable adhesive restoration effects.

OBJECTIVE To explore the influential factors for “Internet +” prescription circulation and construction specifications of prescription circulation platform， so as to provide reference for the government to formulate relevant policies and standardized construction of prescription circulation platform. METHODS Stakeholders in the process of prescription circulation service in medical institutions in Sichuan province were selected to conduct key insider interviews， and grounded theory was used to analyze the data. RESULTS The influential factors of prescription circulation could be divided into three aspects： participant factor， administrative decision factor and information technology factor. The influential factors of prescription circulation mainly lay in pharmacy admission and withdrawal mechanism， medical insurance reimbursement service， supporting policies and pharmaceutical care ability. In terms of pharmacy admission and withdrawal mechanism， pharmacy qualification， pharmaceutical service personnel， drug allocation and distribution should be considered to unify pharmacy admission standards； in terms of medical insurance reimbursement service， it should actively connect with social pharmacies to realize the transfer of prescription medical insurance reimbursement from designated pharmacies； in terms of supporting policies， it should pay attention to the construction of the top-level design of prescription circulation； in terms of pharmaceutical care ability， regular training and assessment of licensed pharmacists should be performed in drug consultation， prescription review and other pharmaceutical care. CONCLUSIONS Participants have more influence on prescription circulation， and pharmacy admission and withdrawal mechanism and pharmaceutical care ability need to be improved. There are various types of prescription circulation platform construction， but each has its own advantages and disadvantages. It is suggested that relevant government departments should improve the access threshold of pharmacies， follow up medical insurance reimbursement services and supporting policies， and explore ways to improve pharmaceutical care capacity， leading and issuing relevant policies and measures to promote the prescription circulation service and make the “Internet +” prescription circulation develop in an orderly manner.