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.

AIM To investigate the variation rules of main secondary metabolites in Hedysari Radix before and after rubbing strip.METHODS UPLC-MS/MS was adopted in the content determination of formononetin,ononin,calycosin,calycosin-7-glucoside,medicarpin,genistein,luteolin,liquiritigenin,isoliquiritigenin,vanillic acid,ferulic acid,γ-aminobutyric acid,adenosine and betaine,after which cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were used for chemical pattern recognition to explore differential components.RESULTS After rubbing strip,formononetin,calycosin,liquiritigenin and γ-aminobutynic acid demonstrated increased contents,along with decreased contents of ononin,calycosin-7-glucoside and vanillic acid.The samples with and without rubbing strip were clustered into two types,calycosin-7-glucoside,formononetin,γ-aminobutynic acid,vanillic acid,calycosin-7-glucoside and formononetin were differential components.CONCLUSION This experiment clarifies the differences of chemical constituents in Hedysari Radix before and after rubbing strip,which can provide a reference for the research on rubbing strip mechanism of other medicinal materials.

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.

Objective:To select chest CT image patterns for the diagnosis of pneumoconiosis and establish a method for determining the profusion of circular small shadows in chest CT.Methods:In April 2021, 66 cases of occupational pneumoconiosis patients with digital radiography (DR) chest radiographs and chest CT imaging data with circular small shadow as the main manifestations were selected as the study objects. 1.5 mm and 5 mm chest CT axial images, 1 mm and 5 mm chest CT coronal multi-plane recombination (MPR) images, and 5 mm chest CT coronal maximum intensity projection (MIP) images were used to observe the different characteristics of pneumoconiosis patients, and were compared and analyzed with DR chest radiographs to establish the experimental chest CT standards. The consistency of the profusion results between the experimental chest CT standards and GBZ 70-2015 Diagnosis of Occupational Pneumoconiosis was verified.Results:All the 66 objects were male, including 33 cases of stage Ⅰ pneumoconiosis, 17 cases of stage Ⅱ pneumoconiosis and 16 cases of stage Ⅲ pneumoconiosis. By observing five chest CT images of 66 objects, we found that chest CT images of different modes could clearly display and identify abnormal images such as small circular shadow, large shadow, small shadow aggregation, honeycomb glass shadow, flake glass shadow, uniform low-profusion glass shadow, mesh glass shadow, cable shadow, linear shadow, subpleural spinous shadow, subpleural nodules, various kinds of emphysema and lung texture distortion and fracture. Small shadow aggregation was usually accompanied by the appearance of large shadow. The vascular shadows in 5 mm CT images had good ductility, and small nodules were easy to distinguish. The coronal MIP image of 5 mm chest CT used edge enhancement technology, which was prone to small shadow fusion and fibrotic shadow fusion. The coronal MPR image of 5 mm chest CT was highly consistent with the DR chest radiographs in terms of the integrity of film reading. GBZ 70-2015 standard was used to compare the profusion of DR chest radiographs and 5 mm chest CT coronal MPR images of 66 objects, and the consistency test Kappa=0.64. GBZ 70-2015 standard and experimental chest CT standard were used to compare the profusion results of DR chest radiographs and 5 mm chest CT coronal MPR images of 66 objects, respectively, and the consistency test Kappa=0.80, with high consistency.Conclusion:5 mm coronal MPR image is suitable for chest CT imaging in the diagnosis of pneumoconiosis. Following the selection path and method of GBZ 70-2015 profusion criterion, the established experimental chest CT standard in determining the profusion of small circular shadows in 5 mm coronal MPR images of chest CT with pneumoconiosis has a high consistency with GBZ 70-2015 standard.

Objective:To select chest CT image patterns for the diagnosis of pneumoconiosis and establish a method for determining the profusion of circular small shadows in chest CT.Methods:In April 2021, 66 cases of occupational pneumoconiosis patients with digital radiography (DR) chest radiographs and chest CT imaging data with circular small shadow as the main manifestations were selected as the study objects. 1.5 mm and 5 mm chest CT axial images, 1 mm and 5 mm chest CT coronal multi-plane recombination (MPR) images, and 5 mm chest CT coronal maximum intensity projection (MIP) images were used to observe the different characteristics of pneumoconiosis patients, and were compared and analyzed with DR chest radiographs to establish the experimental chest CT standards. The consistency of the profusion results between the experimental chest CT standards and GBZ 70-2015 Diagnosis of Occupational Pneumoconiosis was verified.Results:All the 66 objects were male, including 33 cases of stage Ⅰ pneumoconiosis, 17 cases of stage Ⅱ pneumoconiosis and 16 cases of stage Ⅲ pneumoconiosis. By observing five chest CT images of 66 objects, we found that chest CT images of different modes could clearly display and identify abnormal images such as small circular shadow, large shadow, small shadow aggregation, honeycomb glass shadow, flake glass shadow, uniform low-profusion glass shadow, mesh glass shadow, cable shadow, linear shadow, subpleural spinous shadow, subpleural nodules, various kinds of emphysema and lung texture distortion and fracture. Small shadow aggregation was usually accompanied by the appearance of large shadow. The vascular shadows in 5 mm CT images had good ductility, and small nodules were easy to distinguish. The coronal MIP image of 5 mm chest CT used edge enhancement technology, which was prone to small shadow fusion and fibrotic shadow fusion. The coronal MPR image of 5 mm chest CT was highly consistent with the DR chest radiographs in terms of the integrity of film reading. GBZ 70-2015 standard was used to compare the profusion of DR chest radiographs and 5 mm chest CT coronal MPR images of 66 objects, and the consistency test Kappa=0.64. GBZ 70-2015 standard and experimental chest CT standard were used to compare the profusion results of DR chest radiographs and 5 mm chest CT coronal MPR images of 66 objects, respectively, and the consistency test Kappa=0.80, with high consistency.Conclusion:5 mm coronal MPR image is suitable for chest CT imaging in the diagnosis of pneumoconiosis. Following the selection path and method of GBZ 70-2015 profusion criterion, the established experimental chest CT standard in determining the profusion of small circular shadows in 5 mm coronal MPR images of chest CT with pneumoconiosis has a high consistency with GBZ 70-2015 standard.

Objective:To fabricate the composite scaffolds for bone regeneration with silk fibroin (SF), bacterial cellulose nanofibers (BCNR) and hydroxyapatite (HAp) and evaluate their osteogenic activity.Methods:HAp particles, BCNR and bone morphogenetic protein-2 (BMP2) were added into SF aqueous solution in turn, poured into molds of different sizes after being mixed evenly and processed at -25 ℃ for 24 hours to obtain frozen molds, and the composite scaffolds were frozen-dried by freezing-drying machine. The composite scaffolds with different mass ratios of SF and BCNR were divided into groups A (2∶1), B (4∶1) and C (6∶1), and the inactive composite scaffolds without BMP2 fell into group D. The surface morphology and pore structure of the scaffolds were detected by scanning electron microscopy. The porosity of the scaffolds was measured by mercury intrusion porosimeter. The stress-strain curve was obtained by using the universal material testing machine to compress the scaffolds, with which their compressive strength and Young′s modulus were analyzed. Immortalized mouse embryonic fibroblasts (iMEF) were inoculated on the composite scaffolds of group A, B, C and D. At 4 and 8 days after cell inoculation, the proportion of alive and dead cells in each group was detected by cell survival/death staining; the cell counting kit-8 (CCK-8) was used to detect cell proliferation activity in each group; the positive staining cells were detected in each group by alkaline phosphatase (ALP) staining; the ALP activity was observed in each group with ALP activity detection. A total of 15 female SD rats were selected to establish osteogenesis models with ectopic muscle bag. The composite scaffolds implanted with different SF/BCNR mass ratios and the inactive composite scaffolds without BMP2 fell into group A′ (2∶1), B′ (4∶1), C′ (6∶1) and D′ respectively, and a sham operation group was set at the same time, with 3 rats in each groups. In the sham operation group, the muscle bag and skin were sutured without scaffold implantation after the incision of skin, the blunt separation of the quadriceps muscle, and the formation of muscle bag in the muscle. In the other four groups, the corresponding scaffolds were implanted in the muscle bag and the muscle bag and skin were sutured. X-ray examination was performed at 2 and 4 weeks after operation to observe the osteogenesis in each group. At 4 weeks after operation, the implanted scaffolds and tissue complexes were collected by pathological tissue sectioning, HE staining and Masson staining, and for observing the osteogenesis by in each group. Immunohistochemical staining was also performed on the tissue sections to observe the expression of osteogenic markers type I collagen (COL1) and osteopontin (OPN) in each group.Results:Scanning electron microscopy showed that the lamellar and micropore structures of group B were more regular and uniform than those of groups A and C. The porosity rate analysis showed that the porosity rates of groups B and C were (89.752±1.866)% and (84.257±1.013)% respectively, higher than that of group A [(81.171±1.268)%] ( P<0.05 or 0.01), with the porosity rate of group C lower than that of group B ( P<0.01). The mechanical property test showed that the compressive strengths of groups B and C were (0.373±0.009)MPa and (0.403±0.017)MPa respectively, higher than that of group A [(0.044±0.003)MPa] ( P<0.01), and the Young′s moduli of groups B and C were (7.413±0.094)MPa and (9.515±0.615)MPa respectively, higher than that of group A [(1.881±0.036)MPa] ( P<0.01), with the compressive strength and Young′s modulus of group C higher than those of group B ( P<0.05 or 0.01). The cell survival/death staining showed that the number of dead cells of group B was significantly smaller than that of groups A, C and D at 4 days after cell inoculation, and that group B had the most living cells and the fewest dead cells at 8 days after cell inoculation. The results of CCK-8 experiment showed that at 4 days after cell inoculation, the cell proliferation activity of groups A and B was 0.474±0.009 and 0.545±0.018 respectively, higher than 0.394±0.016 of group D ( P<0.01); the cell proliferation activity of group C was 0.419±0.005, with no significant difference from that of group D ( P>0.05), while the cell proliferation activity of groups A and C were both lower than that of group B ( P<0.01). At 8 days after cell inoculation, the cell proliferation activity of group B was 1.290±0.021, higher than 1.047±0.011 of group D ( P<0.01); the cell proliferation activity of group C was 0.794±0.032, lower than that of group D ( P<0.01); the cell proliferation activity of group A was 1.086±0.020, with no significant difference from that of group D ( P>0.05); the cell proliferation activity of groups A and C was lower than that of group B ( P<0.01). At 4 and 8 days after cell inoculation, ALP staining showed that more positive cells were found in groups A, B and C when compared with group D, and more positive cells were found in group B than in groups A and C. At 4 days after cell inoculation, the ALP activity detection showed that the ALP activity of groups A, B and C was 1.399±0.071, 1.934±0.011 and 1.565±0.034 respectively, higher than 0.082±0.003 of group D ( P<0.01), while the ALP activity of groups A and C was lower than that of group B ( P<0.01). At 8 days after cell inoculation, the cell activity of groups A, B and C was 2.602±0.055, 3.216±0.092 and 2.145±0.170 respectively, higher than 0.101±0.001 of group D ( P<0.01), while the ALP activity of groups A and C was lower than that of group B ( P<0.01). X-ray examination results showed that at 2 weeks after operation, no obvious osteogenesis was observed in the sham operation group, group D′, A′ and C′, while it was observed in group B′. At 4 weeks after operation, obvious osteogenesis was observed in group A′, B′ and C′, with significantly more osteogenesis in group B′ than in the other two groups, while there was no obvious osteogenesis in the sham operation group and group D′. At 4 weeks after operation, the HE staining and Masson staining showed that a large number of uniformly distributed new bone tissue was formed in group B′, while only a small amount of new bone tissue was found locally in groups A′ and C′, and only part of new tissue was found to grow in group D′ with no obvious new bone tissue observed. The maturity of new bone tissue formed in group B′ was higher than that in group A′ and C′. Immunohistochemical staining showed more COL1 and OPN positive staining in group B′ when compared with groups A′ and C′. The expression intensity analysis of COL1 and OPN showed that in groups A′, B′ and C′, the expression intensity of COL1 was 2.822±0.384, 22.810±2.435 and 12.480±0.912 respectively and the expression intensity of OPN was 1.545±0.081, 5.374±0.121 and 2.246±0.116 respectively, with higher expression intensity of COL1 and OPN in groups B′ and C′ than that in group A′ ( P<0.01) and lower expression intensity of COL1 and OPN in group C′ than that in B′ group ( P<0.01). Conclusions:The composite scaffold for bone regeneration is successfully fabricated with SF, BCNR and HAp. The composite scaffold with a mass ratio of SF to BCNR of 4∶1 has uniform pore structure, high porosity, good mechanical properties and biocompatibility, excellent pro-osteogenic properties in vitro, as well as excellent osteo-inductivity and osteo-conductivity.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To evaluate the performance of our self-developed deep learning (DL) model which was designed to automatically classify the knee X-ray images into one non-surgical category and 4 surgical categories, including non-surgical knees (NSK), high tibial osteotomy (HTO), total knee arthroplasty (TKA), unicompartmental knee arthroplasty (UKA), and tibial plateau fracture fixation with an internal fixation plate (TPFF).Methods:The knee X-ray images were collected of the patients who had undergone knee joint surgery at Department of Orthopaedics, Fuzhou Second General Hospital from January 2017 to December 2022. On the Baidu EasyDL AI platform, a multi-class object recognition DL model was built using the You Only Look Once (YOLO) algorithm. The model was trained on a dataset of 1,281 knee anteroposterior X-ray images (including NSK, HTO, TKA, UKA, and TPFF) to generate a DL model which was able to automatically recognize and classify the knee X-ray images. The reliability of the model classification performance was evaluated by analyzing the 5 indicators [accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV)] using a test set of 450 knee anteroposterior X-ray images with the above 5 categories. The receiver operating characteristic curve was plotted and the area under the curve (AUC) was calculated to further quantify the classification performance of the model.Results:In the test set, on the whole, the model achieved an accuracy of 97.0%, a sensitivity of 92.4%, a specificity of 98.1%, a PPV of 92.4%, and a NPV of 98.1%, an AUC of 0.947, indicating a high reliability in classifying various categories. The model showed a best performance for TKA, with the 5 indicators being 99.1%, 99.0%, 99.1%, 97.1% and 99.7%. The model showed a slightly lower sensitivity for TPFF and HTO (87.0% and 86.0%, respectively).Conclusion:A successful DL model has been developed which can automatically classify the knee X-ray images into non-surgical and surgical categories due to its satisfactory performance, particularly in accuracy and AUC.

Objective To preliminarily evaluate the safety and effectiveness of a novel non-implantable atrial shunt device based on radiofrequency ablation for the treatment of chronic heart failure(CHF).Methods This was a prospective single-arm study.From January 2023 to December 2023,five eligible CHF patients were consecutively enrolled at Beijing Anzhen Hospital,Capital Medical University,and underwent inter-atrial shunt using Shenzhen Betterway atrial shunt device.Pulmonary capillary wedge pressure(PCWP),right atrial pressure(RAP),pulmonary artery pressure(PAP),total pulmonary resistance(TPR),pulmonary vascular resistance(PVR),and pulmonary/systemic blood flow ratio(Qp/Qs)were measured using right heart catheterization before and immediately after procedure.Patients were followed up for 90 days,and echocardiography,right heart catheterization,and cardiac functional indicators were evaluated.The primary endpoint was procedural success.Secondary endpoints included clinical success,echocardiographic changes,6-minute walk distance(6MWD)changes,New York Heart Association(NYHA)class changes,Kansas city cardiomyopathy questionnaire(KCCQ)score changes,and amino-terminal probrain natriuretic peptide(NT-proBNP)level changes at 90 days.The safety endpoint was major cardiovascular and cerebrovascular adverse events and device-related adverse events.Results All five patients successfully achieved left-to-right atrial shunt.Compared with baseline,PCWP decreased significantly immediately after procedure in all five patients,with a procedural success rate of 100％.There were no significant changes in RAP,PAP,TPR,and PVR before and immediately after procedure.After 90 days follow-up,four patients had persistent left-to-right atrial shunt,and PCWP was significantly lower than baseline,with a clinical success rate of 80％.Compared with baseline,LVEF increased,left ventricular end-diastolic diameter decreased,and tricuspid annular plane systolic excursion and right ventricular fractional area change were not impaired in all five patients at 90 days.KCCQ scores and 6MWT improved,NT-proBNP decreased,and NYHA class did not change significantly.There were no deaths,rehospitalizations for heart failure,stroke-related adverse events,or device-related adverse events during the follow-up.Conclusions The novel non-implantable atrial shunt catheter can safely and effectively improve hemodynamic,echocardiographic,and cardiac functional indicators in patients with heart failure.However,larger-scale clinical studies are still needed to validate its long-term clinical effectiveness.

Objective:To investigate the distribution rules of artemisia pollen and the clinical sensitization characteristics of allergic rhinitis (AR) induced by artemisia pollen in three urban and rural areas of Inner Mongolia.Methods:From March to October 2019, in 3 central cities (Chifeng, Hohhot, Ordos) and rural areas of Inner Mongolia, an epidemiological investigation method combining multi-stage stratified random sampling and face-to-face questionnaire survey was adopted to screen suspected AR patients, and skin prick test (SPT) was applied for diagnosis. At the same time, pollen monitoring was carried out in 3 areas to analyze the distribution and clinical sensitization characteristics of artemisia pollen.SPSS26.0 statistical software was used to process all the data. Chi-square test was used to compare rates among different age, sex, region and nationality, Spearman test was used to describe correlation analysis, and pairwise comparison of positive rates among multiple samples was used Bonferroni method.Results:Among the 6 393 subjects, 1 093 cases were diagnosed with AR, and the prevalence of AR was 17.10% (1 093/6 393). Among them, pollen-induced allergic rhinitis, the prevalence of PiAR was 10.97% (701/6 393), accounting for 64.14%(701/1 093).The highest incidence was in the youth group (20-39 years old), accounting for 46.94% (329/701).The diagnosed prevalence was higher in females than in males (11.35% vs. 10.64%, χ2 value 12.304, P<0.001).The prevalence rate of ethnic minority was higher than that of Han nationality (13.01% vs. 10.65%, χ2 value 6.296, P=0.008).The prevalence in urban areas was also significantly higher than that in rural areas (18.40% vs. 5.50%, χ2 value 10.497, P<0.001).There was significant difference in prevalence rate among the three regions in Inner Mongolia (6.06% in Chifeng, 13.46% in Hohhot, 16.39% in Ordos, χ2 value 70.054, P<0.001).The main clinical symptoms of artemisia PiAR were sneezing (95.58%), nasal congestion (91.73%) and nasal itching (89.30%).Allergic conjunctivitis accounted for 79.60% (558/701), chronic sinusitis for 55.63% (390/701), asthma for 23.25% (163/701).The pattern of artemisia pollen sensitization was mainly multiple sensitization, and the frequency of clinical symptoms and clinical diseases induced by hypersensitization with other allergens accounted for more than that caused by single artemisia pollen. The spread period of Artemisia pollen in the three regions was from June to October, and the peak state was in August in summer. The peak time of clinical symptoms in artemisia PiAR patients was about 2 weeks earlier than the peak time of pollen concentration, and the two were significantly positively correlated ( R=0.7671, P<0.001). Conclusion:Artemisia pollens are the dominant pollens in late summer and early autumn in Inner Mongolia, and the prevalence of artemisia PiAR is high. Controlling the spread of Artemisia pollens is of great significance for the prevention and treatment of AR.