With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.

DNA origami is a powerful technique for generating nanostructures with dynamic properties and intelligent controllability. The precise geometric shapes, high programmability, and excellent biocompatibility make DNA origami nanostructures an emerging drug delivery vehicle. The shape, size of the carrier material, as well as the loading and release of drugs are important factors affecting the bioavailability of drugs. This paper focuses on the controllable design of DNA origami nanostructures, efficient drug loading, and intelligent drug release. It summarizes the cutting-edge applications of DNA origami technology in biomedicine, and discusses areas where researchers can contribute to further advancing the clinical application of DNA origami carriers.

This study using maltodextrin as raw material, 1%-5% polyvinylpyrrolidone K30 as template agent, 1%-5% ammonium bicarbonate as pore-forming agent, curcumin and ibuprofen as model drugs. Porous maltodextrin was prepared by template and pore-forming agent methods, respectively. The structure and drug delivery behavior of porous maltodextrin prepared by different technologies were comprehensively characterized. The results showed that the porous maltodextrin prepared by pore-forming agent method had larger specific surface area (6.449 4 m²·g^-1) and pore size (32.804 2 nm), which was significantly better than that by template agent method (3.670 2 m²·g^-1, 15.278 5 nm). The adsorption kinetics between porous maltodextrin prepared by pore-forming agent method and curcumin were suitable for quasi-first order adsorption kinetic model, and that between porous maltodextrin and ibuprofen were suitable for quasi-second order adsorption kinetic model. While the adsorption kinetics between porous maltodextrin prepared by template agent method and two model drugs were both suitable for the quasi-first order adsorption kinetic model. In addition, the dissolution behavior analysis showed that the porous maltodextrin prepared by the two technologies can significantly improve the dissolution behavior of insoluble drugs, and the drug release was both carried out by diffusion mechanism, which suitable for the Peppas kinetic release model, but the porous maltodextrin prepared by template agent method had a faster release rate. The change of nozzle diameter had no significant effect on the adsorption process and drug release behavior of porous maltodextrin. In conclusion, the porous maltodextrins prepared by two different technologies were both beneficial to the delivery of insoluble drugs, and the template agent method was the best for delivery of insoluble drugs. This study can provide theoretical basis for the preparation of porous particles, promote the application of porous particles in insoluble drugs, and improve the bioavailability of insoluble drugs.

Objective To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine(MDMA)and its metabolite 4,5-methylene dioxy amphetamine(MDA)in rats af-ter single and continuous administration of MDMA,providing reference data for the forensic identifica-tion of MDMA.Methods A total of 24 rats in the single administration group were randomly divided into 5,10 and 20 mg/kg experimental groups and the control group,with 6 rats in each group.The ex-perimental group was given intraperitoneal injection of MDMA,and the control group was given intraperi-toneal injection of the same volume of normal saline as the experimental group.The amount of 0.5 mL blood was collected from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.In the continuous administration group,24 rats were randomly divided into the experi-mental group(18 rats)and the control group(6 rats).The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5,7,9,11,13,15,17 mg/kg per day,respectively,while the control group was given the same volume of normal saline as the experimental group by in-traperitoneal injection.On the eighth day,the experimental rats were randomly divided into 5,10 and 20 mg/kg dose groups,with 6 rats in each group.MDMA was injected intraperitoneally,and the con-trol group was injected intraperitoneally with the same volume of normal saline as the experimental group.On the eighth day,0.5 mL of blood was taken from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels,and statistical software was employed for data analysis.Results In the single-administration group,peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration,respectively,with the largest detection time limit of 12 h.In the continuous administration group,peak concentrations were reached at 30 min and 1.5 h af-ter administration,respectively,with the largest detection time limit of 10 h.Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows:T=10.362C-1.183,R2=0.974 6;T=7.397 3C-0.694,R2=0.961 5(T:injection time;C:concentration ratio of MDMA to MDA in plasma).Conclusions The toxicokinetic data of MDMA and its metabolite MDA in rats,obtained through single and continuous administration,including peak concentration,peak time,detection time limit,and the relationship between concentration ratio and administration time,provide a theoretical and data foundation for relevant forensic identification.

AIM To establish an UPLC-MS/MS method for simultaneous content determination of protocatechuic acid,epicatechin,chlorogenic acid,quercitrin,gaultherin and gaultheroside A in Gaultheria leucocarpa var.yunnanensis.METHODS The analysis was performed on a 40℃thermostatic Waters BEH C18 column(100 mm×2.1 mm,1.7 μm),with the mobile phase comprising of water(containing 0.1%formic acid)-acetonitrile(containing 0.1%formic acid)flowing at 0.3 mL/min in a gradient elution manner,and electron spray inoization source was adopted in positive and negative ion scanning with multiple reaction monitoring(MRM)mode.Hierarchical cluster analysis(HCA)and principal component analysis(PCA)was used to screen important components that affect the quality of medicinal materials.RESULTS Six constituents showed good linear relationships within their own ranges(R2≥0.998 2),whose average recoveries were 98.76%-101.88%with the RSDs of 1.0%-2.5%.The constituents of G.leucocarpa in the roots and aerial parts were quite different.Gaultherin,epicatechin and protocatechuic acid may be the quality mark constituents of G.leucocarpa.CONCLUSION This accurate and efficient method can be used for the quality control of G.leucocarpa.

Objective To investigate the effect of respiratory training based on core stability training on feedforward control in pa-tients with chronic nonspecific low back pain(CNLBP). Methods A total of 60 patients with CNLBP in Jiaxing Second Hospital from January,2022 to March,2023 were ran-domly divided into control group(n=30)and experimental group(n=30).Both groups received health educa-tion,physical factor therapy and core stability training,while the experimental group received respiratory training in addition,for four weeks.Visual Analogue Scale(VAS)score,Japanese Orthopaedic Association low back pain(JOA)score and Oswestry Dysfunction Index(ODI)were compared between two groups before and after treat-ment,while surface electromyography was used to detect the root mean square(RMS)and integrated electromy-ography(iEMG)of transversus abdominis,multifidus and triceps(movement muscles),and the activation se-quence and relative activation time of transversus abdominis,multifidus and triceps were calculated. Results After treatment,the scores of VAS,JOA and ODI improved significantly in both groups(|t|>8.515,P<0.001),and the scores were better in the experimental group than in the control group(|t|>2.089,P<0.05).RMS and iEMG of transversus abdominis and multifidus improved significantly after treatment in both groups(|t|>18.831,P<0.001),and were significantly better in the experimental group(|t|>3.481,P<0.05).The transversus abdominis and multifidus in both groups were activated before the movement muscles,and the relative activation time of transversus abdominis and multifidus increased in negative(|t|>48.115,P<0.001),the experimental group being better(|t|>3.229,P<0.05). Conclusion Combination of core stability training and respiratory training is beneficial in reducing the pain of patients with CNLBP,reducing the lumbar dysfunction,improving the order of muscle activation,and strengthening feed-forward control.

Purpose::The toughest challenge in pedestrian traffic accident identification lies in ascertaining injury manners. This study aimed to systematically simulate and parameterize 3 types of craniocerebral injury including impact injury, fall injury, and run-over injury, to compare the injury response outcomes of different injury manners.Methods::Based on the total human model for safety (THUMS) and its enhanced human model THUMS-hollow structures, a total of 84 simulations with 3 injury manners, different loading directions, and loading velocities were conducted. Von Mises stress, intracranial pressure, maximum principal strain, cumulative strain damage measure, shear stress, and cranial strain were employed to analyze the injury response of all areas of the brain. To examine the association between injury conditions and injury consequences, correlation analysis, principal component analysis, linear regression, and stepwise linear regression were utilized.Results::There is a significant correlation observed between each criterion of skull and brain injury ( p < 0.01 in all Pearson correlation analysis results). A 2-phase increase of cranio-cerebral stress and strain as impact speed increases. In high-speed impact (> 40 km/h), the Von Mises stress on the skull was with a high possibility exceed the threshold for skull fracture (100 MPa). When falling and making temporal and occipital contact with the ground, the opposite side of the impacted area experiences higher frequency stress concentration than contact at other conditions. Run-over injuries tend to have a more comprehensive craniocerebral injury, with greater overall deformation due to more adequate kinetic energy conduction. The mean value of maximum principal strain of brain and Von Mises stress of cranium at run-over condition are 1.39 and 403.8 MPa, while they were 1.31, 94.11 MPa and 0.64, 120.5 MPa for the impact and fall conditions, respectively. The impact velocity also plays a significant role in craniocerebral injury in impact and fall loading conditions (the p of all F-test < 0.05). A regression equation of the craniocerebral injury manners in pedestrian accidents was established. Conclusion::The study distinguished the craniocerebral injuries caused in different manners, elucidated the biomechanical mechanisms of craniocerebral injury, and provided a biomechanical foundation for the identification of craniocerebral injury in legal contexts.

Objective To explore the modal testing method for the three-axis manned centrifuge under elastic boundary conditions with considerations on its complicated structure and high rotational inertia.Methods Modal testing was carried out with a three-axis manned centrifuge under elastic boundary conditions as the subject and a force hammer as the excitation source according to GJB 2706A-2008 Modal tests method for spacecraft and GB/T 11349.3-1992 Experimental determination of mechnical mobility measurements using impact excitation.Four times of hammering were carried out at each excitation position,and the data of the four times of hammering underwent linear average computation.Data acquisition was implemented with a three-axis accelerometer and a 64-channel data collector,and the modal data were analyzed using a frequency response function based on the Test.Lab modal test and analysis software.Results The coherence coefficient of the excitation signal was not lower than 0.8 in the 30 Hz band;the first three orders of the system's intrinsic vibrations were all torsional vibrations,with the frequencies of 9.15,15.66 and 19.22 Hz,respectively;the first order frequency of the system was about 9.15 Hz for both Z18 and Z21 excitation positions,and each of the second and third order frequencies similar situations were observed for also had a roughly equal value for the two excitation positions.Conclusion The force hammer testing method is applicable for the modal testing of the three-axis manned centrifuge,ensuring equipment safety and subject comfort.Referen-ces are provided for the following structural optimization design.[Chinese Medical Equipment Journal,2024,45(8):38-43]

Objective To compare the efficacies of retrograde tibial nailing(RTN)versus minimally invasive percutaneous plate osteosynthesis(MIPPO)in the treatment of distal tibial fractures.Methods A retrospective analysis was conducted on the clinical data of 55 patients with distal tibial fractures who underwent surgery in our hospital.Patients were divided into two groups based on the different surgical methods,patients in the RTN group(n=25)were treated with RTN,and patients in the MIPPO group(n=30)were treated with MIPPO.The surgical parameters(operation time,intraoperative blood loss,intraoperative fluoroscopy times,and success rate of closed reduction),fracture healing time,ankle dorsiflexion range of motion and American Orthopaedic Foot and Ankle Society(AOFAS)ankle-hindfoot scores 6 months after operation and at the last follow-up,and the incidence of complications during perioperative period and follow-up were compared between the two groups.Results The operation time,intraoperative blood loss,and intraoperative fluoroscopy times in the RTN group were significantly shorter/less than those in the MIPPO group(P＜0.05).The ankle dorsiflexion range of motion and AOFAS ankle-hindfoot score 6 months after operation in the RTN group were significantly greater/higher than those in the MIPPO group(P＜0.05).There was no statistically significant difference in the fracture healing time,or ankle dorsiflexion range of motion and AOFAS ankle-hindfoot score at the last follow-up between the two groups(P＞0.05).The success rate of closed reduction in the RTN group was 72.00％,which was lower than that of 96.67％in the MIPPO group(P＜0.05).The incidence of soft tissue-related complications in the RTN group was signifi-cantly lower than that in the MIPPO group(P＜0.05),while there was no statistically significant difference in the overall incidence of complica-tions between the two groups(P＞0.05).Conclusion RTN is an effective minimally invasive surgical technique for the treatment of distal tibial fractures,characterized by minimal trauma,low incidence of soft tissue complications,and fast recovery of joint function compared with MIPPO.

"Rooted in agriculture,rural areas,and farmers;Focused on integration"is an important gripper for Henan College of Animal Husbandry Economics to serve the development of regional agricul-ture and animal husbandry industries for high-level application-oriented universities.The courses of bio-chemistry and molecular biology are the foundational courses for agricultural majors in our school,and are an important carrier for the integration of science and technology in the construction of new agricultural science.In order to achieve the ideological and political goals of the curriculum under the background of the new agricultural curriculum,the course team has built a training platform for students'"agriculture,rural areas,and farmers"sentiments from the aspects of disciplinary development history,practical appli-cation of agriculture,rural areas,alumni excellent cases,ecological civilization,professional ethics,and bioethics through the condensation of ideological and political cases;In the arrangements of ideological and political cases and practical project,industry development,agriculture,rural areas,teacher re-search,school enterprise cooperation projects,and student independent innovation projects were connect-ed and integrated to establish a"fusion"platform for student knowledge application,thereby achieving the sentiment cultivation of students'"rooted in agriculture,rural areas,and farmers"and the enhance-ment of their integration capability.During the teaching process,blended online and offline teaching was applied to transform single classroom teaching into full cycle participation in talent cultivation.By integra-ting ideological and political elements into online tasks before class and teaching in the"six stages"of class and the second classroom after class,ideological and political goals were achieved through challeng-ing,advanced,and innovative knowledge applications.Through curriculum reform,the employment rate of students in the frontline of agriculture,rural areas,and farmers has significantly increased,and their ability to solve the problems of agriculture,rural areas and farmers through disciplinary integration has been effectively improved.This has successfully enhanced their awareness of serving agriculture,rural ar-eas,and farmers,strengthened their professional thinking,and stimulated their endogenous motivation to use curriculum knowledge in practice.