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*

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.

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 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.

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 provide reference for perfecting prescription circulation service and related platforms construction and improving online medical service level. METHODS A questionnaire was designed after literature review and consulting expert opinions. Patients who had received prescription circulation service in the prescription circulation platform of a Grade-A third-class hospital in Sichuan Province from November 22， 2019 to May 2022 were randomly selected， and the knowledge， attitude and practice of prescription circulation service were investigated by questionnaires， which were sent through telephone contact and short message. RESULTS A total of 285 patients were investigated， and the number of effective responses was 200. Most of the surveyed patients in prescription circulation service for 1-5 times in the past year （129 cases， 64.50%）； 77.0% of the patients had a “general understanding” or “no understanding” of prescription circulation services， and the main prescription circulation services they received were online consultation service （169 cases， 84.50%） and drug delivery service （106 cases， 53.00%）. The average waiting time and expected waiting time were 1-5 min. The services with the largest number of demand （145 cases， 72.50%） and the highest demand （3.585 points） were drug delivery services. Most of the respondents’ willingness to pay was “general willingness” （83 cases， 41.50%）， and most of the patients were willing to pay less than or equal to 5 yuan per time （92 cases， 46.00%）. Totally 73.0% of the surveyed patients were “satisfied” or “relatively satisfied” with the prescription transfer service. The results of univariate analysis showed that the main factors influencing patients’ satisfaction with prescription circulation service were service awareness， service waiting time， patients’ demand satisfaction and patients’ willingness to pay. CONCLUSIONS The surveyed patients are generally satisfied with prescription circulation service， and the service content with high satisfaction is drug distribution service， and patients are willing to pay a lower price for prescription circulation service. It is suggested that relevant departments should strengthen the publicity of prescription circulation service， improve the content of prescription circulation service and reduce the payment price of prescription circulation service， so as to improve the operation efficiency of Chinese medical system while facilitating patients.

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.

Objective:To establish an intelligent registration algorithm under the framework of original-mirror alignment algorithm to construct three-dimensional (3D) facial midsagittal plane automatically. Dynamic Graph Registration Network (DGRNet) was established to realize the intelligent registration, in order to provide a reference for clinical digital design and analysis.Methods:Two hundred clinical patients without significant facial deformities were collected from October 2020 to October 2022 at Peking University School and Hospital of Stomatology. The DGRNet consists of constructing the feature vectors of key points in point original and mirror point clouds (X, Y), obtaining the correspondence of key points, and calculating the rotation and translation by singular value decomposition. Original and mirror point clouds were registrated and united. The principal component analysis (PCA) algorithm was used to obtain the DGRNet alignment midsagittal plane. The model was evaluated based on the coefficient of determination (R 2) index for the translation and rotation matrix of test set. The angle error was evaluated on the 3D facial midsagittal plane constructed by the DGRNet alignment midsagittal plane and the iterative closet point (ICP) alignment midsagittal plane for 50 cases of clinical facial data. Results:The average angle error of the DGRNet alignment midsagittal plane and ICP alignment midsagittal plane was 1.05°±0.56°, and the minimum angle error was only 0.13°. The successful detection rate was 78% (39/50) within 1.50° and 90% (45/50) within 2.00°.Conclusions:This study proposes a new solution for the construction of 3D facial midsagittal plane based on the DGRNet alignment method with intelligent registration, which can improve the efficiency and effectiveness of treatment to some extent.

Objective:To evaluate the safety and efficacy of intra-arterial tirofiban infusion during endovascular reperfusion therapy in patients with acute cardiogenic cerebral embolism.Methods:Clinical data of 72 patients with acute cardiogenic cerebral embolism caused by large artery occlusion were retrospectively analyzed in Department of Neurology, Strategic Support Force Medical Center from August 2015 to August 2020.Among those, 52 patients were treated with intra-arterial tirofiban, the other 20 patients were treated with control medication. The baseline characteristics, modified thrombolysis in cerebral infarction (mTICI) score of responsible vessels, modified Rankin scale (mRS) score 90 days after operation, incidence of symptomatic intracranial hemorrhage and mortality were evaluated and compared in two groups.Results:The proportion of effective recanalization of the offending vessels (mTICI≥2b) in tirofiban group was higher than that in control group (92.3% vs. 75.0%), but the difference was not statistically significant ( P=0.104). At 90 days after operation, the rate of patients with good prognosis (mRS≤2) in tirofiban group (61.5%) was significantly higher than that in control group (35.0%) ( P<0.05). The incidence of symptomatic intracranial hemorrhage and mortality were comparable between the two groups ( P>0.05). Conclusion:Intra-arterial tirofiban infusion in patients with acute cardiogenic cerebral embolism is effective and feasible, which improves the prognosis without increasing the risk of intracranial bleeding complications.

To explore the technical process and the therapeutic effect of using sequential surgical guide with independent intellectual property rights assisting immediate implantation and restoration of the full arch, with the support from the periodontal splint for mobile supporting teeth, patients with severe periodontitis who planned to undergo immediate full arch implantation were recruited from August 2019 to December 2020 at the Department of Prosthodontics, Department of Periodontology, Department of Implantology and First Clinical Division, Peking University School and Hospital of Stomatology. Through the procedure of collecting preoperative maxillofacial data, making systematic diagnostic design, making periodontal splints fixation, producing surgical guide, and carrying out guided surgery for full arch immediate implantation, eight cases were included. By registering the postoperative cone-beam CT (CBCT) with the preoperative data, the difference between the actual three-dimensional position of the implants and the virtual design was observed, and the accuracy of the implant placement position guided by the sequential guide was statistically analyzed using SPSS 25.0 software. Analysis indicators include coronal and apical global displacement, coronal horizontal and vertical displacement, apical horizontal and vertical displacement, and angular deviation. Results revealed that the 8 patients [2 males and 6 females, aged (49.0±9.3) years (38-65 years)] of recruited cases included 7 cases of maxilla and 1 cases of mandible. A total of 48 implants, of which 44 implants were placed upright and 4 were placed tilted, 16 implants in the anterior region and 32 implants in the posterior region. No guide plate fracture or damage to important anatomical structures were reported. The overall displacement at the coronal point [(0.83±0.48) mm] and the global displacement at the apical point [(1.36±0.57) mm] were within the clinically acceptable safety range, and the horizontal displacement and vertical displacement at the coronal point, horizontal displacement and vertical displacement at the apical point, and the angle deviation of implants axial have no statistic significant difference in the anterior and posterior region ( P>0.05). Periodontal splints combined with sequential surgical guides to assist patients with severe periodontitis for immediate full arch implantation and immediate restoration can expand the indications of guide assisted implant surgery. It meets the safety requirements in clinical applications.