Objective To construct a glioma microfluidic chip model to simulate tumor microenvironment for evaluating the medicinal efficacy of anti-glioma traditional Chinese medicines. Methods Glioblastoma cells U251 were seeded into microfluidic chips with different culture modes, and the cell viability and tumour microenvironment within the constructed model were characterized. Fluorescence staining was used to evaluate the effects of the positive drugs temozolomide （TMZ） and docetaxel （DOC） on the cell activity and apoptosis within the model, which was applied to evaluate the medicinal efficacy of the extracts of the herb Scutellaria barbata on gliomas. Results The cells in the constructed U251 microfluidic chip model displayed high viability and were able to mimic the hypoxic microenvironment of tumor to a certain extent. The viability of the U251 cells in the microfluidic chips decreased with the increasing of the concentration of the positive drug, and the viability of the 3D cultured U251 cells was higher than that in the 2D condition （P<0.05）. The intracellular mitochondrial membrane potential decreased with the increasing of the concentration of the positive drug. And the 2 mg/ml Scutellaria barbata extract killed U251 cells to a certain extent and reduced the mitochondrial membrane potential of the cells in the model. Conclusion This study successfully constructed a microfluidic chip model of glioma that could effectively simulate the tumor microenvironment and rapidly evaluate the anti-tumor medicinal efficacy, which provided a new strategy for the medicinal efficacy evaluation and active components screening of anti-glioma traditional Chinese medicines.

Objective To evaluate the efficacy of Puerariae lobatae radix （PLR） and Anemarrhenae Rhizoma （AR） in preventing and treating Alzheimer’s disease （AD） and explore its potential mechanism of action by LC-MS serum metabolomics strategy. Methods The AD rat model was established by administering aluminum chloride （AlCl₃） and D-galactose （D-gal） for 20 weeks. The traditional Chinese medicine intervention group was given the PLR, AR, and PLR-AR extracts for 8 weeks by gavage. The model effect and efficacy were evaluated by Morris water maze test and biochemical indicators including SOD, NO, and MDA; Metabolomics research based on the UHPLC-Q/TOF-MS method was conducted, and relevant metabolic pathways were analyzed through the MetaboAnalyst online website. Results The learning and memory abilities of AD model rats were significantly decreased compared with the control group, and the levels of oxidative stress and lipid peroxides were significantly increased （P<0.05）, while the SOD content was decreased considerably （P<0.01）. The learning and memory abilities of AD model rats were improved, oxidative stress and lipid peroxidation levels were reversed, and serum SOD content was increased significantly after the intervention of PLR-AR, with better effects than single drugs. Through metabolomics, 70 differential metabolites were identified between the AD model group and the control group, mainly involving 10 pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, and unsaturated fatty acid biosynthesis, et.al. The intervention of PLR-AR could adjust 47 metabolites, with 20 metabolites showing significant differences （P<0.05）. The significantly adjusted metabolites involve 6 pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis, et al. Conclusion The combination of PLR and AR could significantly improve the learning and memory abilities of AD rat models. The mechanism may be related to the improvement of oxidative stress and lipid peroxidation levels, the increase of serum SOD content, and the regulation of phenylalanine, tyrosine, and tryptophan biosynthesis pathways.

Objectives:To investigate the association between normal-weight central obesity with new-onset cardiovascular disease and all-cause mortality risk. Methods:A prospective cohort study was conducted,selecting a total of 93885 participants from the Kailuan Study who had their first physical examination in 2006-2007.According to waist circumference (central obesity:male waist circumference ≥90 cm,female waist circumference ≥85 cm;no central obesity:male waist circumference<90 cm,female waist circumference<85 cm) and body mass index (BMI,normal weight:18.5 kg/m2≤BMI<24.0 kg/m2;overweight/obesity:BMI ≥24.0 kg/m2),the participants were divided into 4 groups:normal weight no central obesity group (G1 group),normal weight central obesity group (G2 group),overweight/obesity no central obesity group (G3 group) and overweight/central obesity group (G4 group);Using the Kaplan-Meier method,the cumulative incidence of new-onset cardiovascular diseases (including hemorrhagic stroke,ischemic stroke and myocardial infarction) and all-cause mortality in different groups was calculated,and the Log-rank test was used for intergroup comparisons.Furthermore,the associations between the different groups and the risk of new-onset cardiovascular diseases and all-cause mortality were analyzed using the multivariate Cox proportional hazard regression model. Results:After a median follow-up of 14.97 (14.55,15.17) years,the cumulative incidence of new-onset cardiovascular diseases in G1 group,G2 group,G3 group and G4 group was 7.62％,10.84％,8.67％,12.91％ respectively (log-rank P<0.05) and the cumulative incidence of all-cause mortality was 12.83％,19.72％,10.65％,16.33％ respectively (log-rank P<0.01).After adjusting for confounding factors,Cox regression analysis showed that the HR (95％CI) of new-onset cardiovascular diseases in G2 group,G3 group and G4 group were 1.14 (1.04-1.25),1.07 (1.01-1.14),1.27 (1.21-1.34),respectively compared with G1 group (all P<0.05).The HR (95％CI) of all-cause mortality were 1.06 (1.00-1.14),0.90 (0.85-0.95),0.97 (0.93-1.01) compared with G1 group,and P values were 0.07,<0.01,0.15,respectively.The results of sensitivity analysis were consistent with the above major studies after excluding overweight/obesity and cancer participants during follow-up. Conclusions:Normal-weight central obesity increases the risk of new-onset cardiovascular diseases and all-cause mortality.

BACKGROUND:There is currently no anatomic locking plate suitable for the anteromedial platform,so the medial locking plate of the tibial plateau is usually placed forward to fix anteromedial compression fractures caused by hyperextension varus injury.Due to the inability of the locking screw to achieve vertical fixation of the fracture line,coupled with the influence of the patellar ligament,the clinical results are still unsatisfactory. OBJECTIVE:To compare the biomechanical performance of a new type of plate with traditional internal fixation methods in treating hyperextension varus tibial plateau fractures through finite element analysis. METHODS:CT data of 20 cases of hyperextension varus tibial plateau fractures were collected,and their morphological characteristics,such as medial posterior tibial slope,the medial articular fracture angle,surface area,and anterior cortical height were measured.A 24-year-old male volunteer with a height of 175 cm and a weight of 65 kg was selected,and his tibial CT data were imported into Mimics 21.0 software to generate a 3D model.Then,internal fixation models were imported into SolidWorks 2017 software.New type of plate,medial locking plate,posterior medial locking plate,and 6.5 mm hollow screws fixed data models were established based on the measured morphological data.Ansys 17.0 software was used to load stress on the four fixation models and compare their biomechanical performance. RESULTS AND CONCLUSION:(1)With the increase of axial load,the peak stresses of different internal fixation models approximately increased proportionally.At 500 N,the peak stress values were as follows:screw group(6.973 7 MPa)

The intestine is the main site of oral drug absorption, and the epithelial cells of the intestine contain villi and microvilli, which promote secretion, cell adhesion, and absorption by increasing surface area and other factors. Traditional two-dimensional/three-dimensional (2D/3D) cell culture models and animal models have played an important role in studying drug absorption, but their application is limited due to the lack of sufficient predictability of human pharmacokinetics or ethical issues, etc. Therefore, mimicking the core structure and key functions of the human intestine based on in vitro live cells has been the focus of research on constructing a microfluidic chip-based intestinal model. The model is a microfluidic chip bionic system that simulates the complex microstructure, microenvironment, and physiological functions of the human intestine using microfabrication technology. Compared with 2D cell culture and animal experiments, the intestinal microarray model can effectively simulate the human in vivo environment and is more specific in drug screening. The research progress and applications in disease modeling, drug absorption and transport of intestinal microarray models and intestine-related multi-organ coupled microarray models at home and abroad were reviewed in this paper. The current challenges of intestinal chip simulating intestinal homeostasis and diseases were summarized，in order to provide reference for the further establishment of a more reliable in vitro intestinal chip model.

Objective To investigate the epidemiological characteristics of local visceral leishmaniasis in Beijing Municipality from 2021 to 2023, so as to provide insights into formulation of the visceral leishmaniasis control strategy. Methods Epidemiological data of visceral leishmaniasis cases reported in Beijing Municipality from 2021 to 2023 were collected from the National Health Informatization Disease Prevention and Control Information System, and the epidemiological characteristics of local visceral leishmaniasis cases were analyzed using a descriptive epidemiological method. In November 2021 and 2023, 50 to 100 permanent residents were voluntarily selected within a 100 meter radius of sites where patients lived or acquired Leishmania infections, and venous blood was sampled for anti-Leishmania antibody testing. Venous blood was sampled from dogs for anti-Leishmania antibody testing in natural villages where patients lived or acquired Leishmania infections, or in districts where Leishmania infected dogs were reported. In addition, sandflies were captured with CO₂ mosquito traps and fine mesh nets in natural villages where patients lived or acquired Leishmania infections from May to September, 2021 and 2023, for sandfly species identification. Results A total of 4 local visceral leishmaniasis cases were reported in Beijing Municipality from 2021 to 2023, with ages of 2 to 77 years, and acquiring Leishmania infections in Mentougou District (2 cases), Changping District (1 case), and Yanqing District (1 case). The anti-Leishmania antibody testing was all negative in 73 human blood samples and the sero-prevalence of anti-Leishmania antibody was 25.00% in 36 venous blood samples from domestic dogs in 2021, with a total of 4 520 Phlebotomus chinensis captured. The sero-prevalence of anti-Leishmania antibody was 0.51% in 198 human blood samples and 13.58% in 243 venous blood samples from domestic dogs in 2023, with 16.10%, 25.00%, 17.78% and 3.13% sero-prevalence in dogs sampled from Mentougou District, Changping District, Yanqing District and Haidian District, respectively (P = 0.011), while a total of 1 712 Ph. chinensis were captured, including 1 421 female sandflies (86.54%). Conclusions The prevalence of local visceral leishmaniasis was low in Beijing Municipality from 2021 to 2023; however, there is a risk of further spread in the epidemic foci. Intensified visceral leishmaniasis surveillance and control is recommended.

Chiral drugs are closely related to the safety and effectiveness of drug use.Most dihydropyridine drugs have chiral carbon atoms,which are used as racemes and produce stereoselective disposal characteristics after entering the body,and may affect the safety and effectiveness of drugs.Therefore,based on the chiral resolution and pharmacokinetic characteristics of this class of drugs,the selection rules of chiral HPLC and CE methods and in vivo analysis applications of this class of drugs in recent years were reviewed.The stereoselective pharmacokinetics of this class of drugs were listed and compared.It was found that some of these drugs had obvious differences in stereoselective pharmacokinetics,and the pharmacokinetics and toxicity in vivo were also different.

Cell metabolomics is an important branch of metabolomics, which could dynamically monitor cell response and metabolic changes after drugs acting on cells, and look for potential biomarkers. Cell metabolomics has been widely used in illustration of disease mechanism, evaluation of drug efficacy and development of new drug through elucidating the pathophysiological mechanism of the disease and the effect of drug treatment intervention. The researches process of cellular metabolomics and its application in central nervous system diseases were reviewed in order to provide theoretical basis for in-depth study of the pathogenesis and prevention and treatment of central nervous system diseases.

Accurate classification of the acetabular injuries and appropriate treatment plan are great challenges for orthopedic surgeons because of the irregular anatomical structure of the acetabulum and aggregation of important vessels and nerves around it. Letournel-Judet classification system has been widely applied to classify acetabular fractures. However, there are several limitations, including incomplete inclusion of fracture types, difficulty in understanding and insufficient guidance for surgical treatment, etc. Serious complications such as traumatic arthritis are common due to wrong classification and diagnosis and improper selection of surgical strategy, which brings a heavy burden to the society and families. Three-column classification, based on anatomic characteristics, has advantages of containing more fracture types and being easy to understand, etc. To solve the problems existing in the diagnosis and treatment process based on Letournel-Judet classification, achieve accurate diagnosis and treatment of patients with acetabular fractures, and obtain satisfactory prognosis, the Orthopedic Trauma Emergency Center of Third Hospital of Hebei Medical University and the Trauma Orthopedic Branch of the Chinese Orthopedic Association organized experts from relevant fields to formulate the Expert consensus on the accurate diagnosis and treatment of acetabular fractures based on three-column classification ( version 2023) in terms of principles of evidence-based medicine. Based on the three-column classification, 15 recommendations were proposed, covering the diagnosis, treatment, complication prevention and management, etc, so as to provide reference for accurate diagnosis and treatment of acetabular fractures.

Cell membrane affinity chromatography has been widely applied in membrane protein (MP)-targeted drug screening and interaction analysis. However, in current methods, the MP sources are derived from cell lines or recombinant protein expression, which are time-consuming for cell culture or purification, and also difficult to ensure the purity and consistent orientation of MPs in the chromatographic stationary phase. In this study, a novel in situ synthesis membrane protein affinity chromatography (iSMAC) method was developed utilizing cell-free protein expression (CFE) and covalent immobilized affinity chromatography, which achieved efficient in situ synthesis and unidirectional insertion of MPs into liposomes in the stationary phase. The advantages of iSMAC are: 1) There is no need to culture cells or prepare recombinant proteins; 2) Specific and purified MPs with stable and controllable content can be obtained within 2 h; 3) MPs maintain the transmembrane structure and a consistent orientation in the chromatographic stationary phase; 4) The flexible and personalized construction of cDNAs makes it possible to analyze drug binding sites. iSMAC was successfully applied to screen PDGFRβ inhibitors from Salvia miltiorrhiza and Schisandra chinensis. Micro columns prepared by in-situ synthesis maintain satisfactory analysis activity within 72 h. Two new PDGFRβ inhibitors, salvianolic acid B and gomisin D, were screened out with K _D values of 13.44 and 7.39 μmol/L, respectively. In vitro experiments confirmed that the two compounds decreased α-SMA and collagen Ӏ mRNA levels raised by TGF-β in HSC-T6 cells through regulating the phosphorylation of p38, AKT and ERK. In vivo, Sal B could also attenuate CCl₄-induced liver fibrosis by downregulating PDGFRβ downstream related protein levels. The iSMAC method can be applied to other general MPs, and provides a practical approach for the rapid preparation of MP-immobilized or other biological solid-phase materials.