OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

Clinical trials represent a pivotal stage in the development of pharmaceutical drugs. Nevertheless， given the unique characteristics of traditional Chinese medicine （TCM） and the diagnostic and treatment principle of syndrome differentiation and treatment in TCM， the clinical evaluation techniques and methods that can comprehensively reflect the characteristics of TCM and are tailored to its specificities are still in need of refinement and innovation. This paper systematically summarizes the key techniques and methods for designing and evaluating the clinical research on the treatment of the spleen and stomach diseases with TCM from three aspects including clinical research design， evaluation， and platform construction， compares domestic and international research landscapes， and proposes for future directions. It is suggested that a multidimensional evaluation system integrating modern medicine and TCM theory should be established， and further innovation is needed in TCM research design and methodologies， leveraging intelligent devices and technologies powered by next-generation information technology to transform clinical data into high-quality TCM evidence. Moreover， standardized and shared platforms for TCM clinical data should be accelerated， so as to provide references for the design， implementation， and evaluation of future clinical research on the treatment of the spleen and stomach diseases with TCM.

Chimeric antigen receptor (CAR) cell therapy offers promising new avenues for the treatment of hepatocellular carcinoma. However, several challenges hinder its full potential. Firstly, the high heterogeneity of hepatocellular carcinoma results in a lack of ideal targets, complica-ting the ability of CAR cells to specifically recognize and effectively eliminate tumor cells. Secondly, the immunosuppressive microenvironment of hepatocellular carcinoma, characterized by regulatory T cells and myeloid-derived suppressor cells, diminishes the efficacy of CAR cell therapy, further affecting treatment efficacy. Additionally, safety concerns such as cytokine release syndrome and neurotoxicity remain significant obstacles to clinical application. Finally, the high cost and complex manufacturing processes involved in CAR cell therapy present major barriers to its widespread use. Future research should focus on optimizing target selection, particularly by identifying hepato-cellular carcinoma specific molecular markers; improving CAR cells resilience in immunosuppre-ssive environments; enhancing safety protocols; and streamlining production methods to reduce costs. Addressing these critical issues will facilitate the broader application of CAR cell therapy in hepatocellular carcinoma and other solid tumors, paving the way for a paradigm shift in cancer treatment. Based on relevant literature and combined it with clinical practice, the authors explore the prospects and challenges of CAR cell therapy for the treatment of hepatocellular carcinoma, aiming to provide new ideas for its clinical application.

Objective To observe the value of global and contextual dual attention U-Net model for segmenting thoracic and lumbar vertebrae in spinal sagittal X-ray images.Methods Totally 600 spinal sagittal X-ray images of 600 patients with adolescent idiopathic scoliosis were retrospectively enrolled.The images were preprocessed,and T4-T12 and L1-L5 were manually annotated as reference standards.The global attention refinement(GAR)module and attention-based atrous spatial pyramid pooling(A-ASPP)module were added to U-Net model,fivefold cross validation method was used for training and validation,and its performance for segmenting sagittal X-ray images was analyzed,and compared with pyramid scene parsing network(PSPNet),visual geometry group(VGG)-UNet and DeepLabv3+.Results The precision,sensitivity and Dice similarity coefficient of global and contextual dual attention U-Net model for segmenting thoracic and lumbar vertebrae in spinal sagittal X-ray images was 90.58％,89.51％,and 90.20％,respectively,which were superior to PSPNet,VGG-UNet and DeepLabv3+.The loss function and mean intersection over union curves showed that it converged quickly and had good generalization ability.Conclusion The global and contextual dual attention U-Net model could effectively segment thoracic and lumbar vertebrae in spinal sagittal X-ray images.

Objective To observe the value of global and contextual dual attention U-Net model for segmenting thoracic and lumbar vertebrae in spinal sagittal X-ray images.Methods Totally 600 spinal sagittal X-ray images of 600 patients with adolescent idiopathic scoliosis were retrospectively enrolled.The images were preprocessed,and T4-T12 and L1-L5 were manually annotated as reference standards.The global attention refinement(GAR)module and attention-based atrous spatial pyramid pooling(A-ASPP)module were added to U-Net model,fivefold cross validation method was used for training and validation,and its performance for segmenting sagittal X-ray images was analyzed,and compared with pyramid scene parsing network(PSPNet),visual geometry group(VGG)-UNet and DeepLabv3+.Results The precision,sensitivity and Dice similarity coefficient of global and contextual dual attention U-Net model for segmenting thoracic and lumbar vertebrae in spinal sagittal X-ray images was 90.58％,89.51％,and 90.20％,respectively,which were superior to PSPNet,VGG-UNet and DeepLabv3+.The loss function and mean intersection over union curves showed that it converged quickly and had good generalization ability.Conclusion The global and contextual dual attention U-Net model could effectively segment thoracic and lumbar vertebrae in spinal sagittal X-ray images.

Chimeric antigen receptor (CAR) cell therapy offers promising new avenues for the treatment of hepatocellular carcinoma. However, several challenges hinder its full potential. Firstly, the high heterogeneity of hepatocellular carcinoma results in a lack of ideal targets, complica-ting the ability of CAR cells to specifically recognize and effectively eliminate tumor cells. Secondly, the immunosuppressive microenvironment of hepatocellular carcinoma, characterized by regulatory T cells and myeloid-derived suppressor cells, diminishes the efficacy of CAR cell therapy, further affecting treatment efficacy. Additionally, safety concerns such as cytokine release syndrome and neurotoxicity remain significant obstacles to clinical application. Finally, the high cost and complex manufacturing processes involved in CAR cell therapy present major barriers to its widespread use. Future research should focus on optimizing target selection, particularly by identifying hepato-cellular carcinoma specific molecular markers; improving CAR cells resilience in immunosuppre-ssive environments; enhancing safety protocols; and streamlining production methods to reduce costs. Addressing these critical issues will facilitate the broader application of CAR cell therapy in hepatocellular carcinoma and other solid tumors, paving the way for a paradigm shift in cancer treatment. Based on relevant literature and combined it with clinical practice, the authors explore the prospects and challenges of CAR cell therapy for the treatment of hepatocellular carcinoma, aiming to provide new ideas for its clinical application.

OBJECTIVE To explore the effect and mechanism of Huiyang Shengji Decoction on wound healing in mice with dia-betic yin syndrome.METHODS SPF C57BL/6 mice were selected,and 24 diabetic ulcer models were established by intraperitoneal injection of streptozotocin and skin defect method.The mice were randomly divided into model group,low-dose,medium-dose and high-dose Huiyang Shengji Decoction groups,with 6 mice in each group.Six mice were selected to establish a common wound model as the blank group.The blank group and model group were treated with distilled water by intragastric administration every day,and the Huiyang Shengji Decoction groups were treated with Huiyang Shengji Decoction by intragastric administration every day.The wounds were photographed every day,and the wound healing rate was recorded.HE staining was used to observe the growth of granulation tis-sue in the wounds.Western blot was used to detect the expression of Axl,Tyro3 and Mertk proteins related to wound efferocytosis.Im-munohistochemistry was used to detect the expression of CD11c in wound tissue.qPCR was used to detect the mRNA expression of TNF-α,IL-1β,IL-10 and TGF-β1 in the wounds.TUNEL staining was used to calculate the number of apoptotic cells(AC)in the wounds.Mouse primary bone marrow dendritic cells(BMDC)were resuspended in 1640 medium containing 10%blank serum or 5%,10%,and 20%Huiyang Shengji Decoction-containing serum.After culturing in a cell culture incubator at 37℃and 5%CO2 for 24 h,the wound endocytosis-related receptors were detected by Western blot.BMDC and AC were co-cultured in vitro,and the phag-ocytic rate of BMDC phagocytosis of AC was detected by flow cytometry.RESULTS The wound healing in each dose group of Huiyang Shengji Decoction was significantly faster than that in the model group(P<0.05).Compared with the model group,the protein expres-sion of Axl and Tyro3 in the wound tissue of mice in the high dose group of Huiyang Shengji Decoction was significantly increased(P<0.01,P<0.000 1),and there was no significant difference in the expression of Mertk protein in the wound tissue of mice in the low,medium and high dose groups(P>0.05).The Huiyang Shengji Decoction significantly inhibited the expression of IL-1β and TNF-α mRNA in the wound tissue(P<0.05),promoted the expression of TGF-β1 and IL-10 mRNA(P<0.05),and the number of AC in the wound after treatment with Huiyang Shengji Decoction was less than that in the model group(P<0.05).In the in vitro experiment,compared with the model group,the protein expression of Axl and Mertk in BMDC in the 20%Huiyang Shengji Decoction-containing serum group was significantly increased(P<0.01,P<0.001),and the protein expression of Tyro3 in the 5%,10%,and 20%Huiy-ang Shengji Decoction-containing serum groups was higher than that in the model group(P<0.01,P<0.001).The phagocytic rate of AC in the Huiyang Shengji Decoction group was higher than that in the model group(P<0.05).CONCLUSION Huiyang Shengji Decoction can enhance the efferocytosis function of dendritic cells(DC),reduce AC aggregation in the wound,promote the disappear-ance of wound inflammation and tissue repair,and accelerate the healing of skin wounds.

Iron overload is strongly associated with heart disease. Ferroptosis is a new form of regulated cell death indicated in cardiac ischemia-reperfusion (I/R) injury. However, the specific molecular mechanism of myocardial injury caused by iron overload in the heart is still unclear, and the involvement of ferroptosis in iron overload-induced myocardial injury is not fully understood. In this study, we observed that ferroptosis participated in developing of iron overload and I/R-induced cardiomyopathy. Mechanistically, we discovered that Parkin inhibited iron overload-induced ferroptosis in cardiomyocytes by promoting the ubiquitination of long-chain acyl-CoA synthetase 4 (ACSL4), a crucial protein involved in ferroptosis-related lipid metabolism pathways. Additionally, we identified p53 as a transcription factor that transcriptionally suppressed Parkin expression in iron-overloaded cardiomyocytes, thereby regulating iron overload-induced ferroptosis. In animal studies, cardiac-specific Parkin knockout mice (Myh6-CreER ^T2 /Parkin ^fl/fl ) fed a high-iron diet presented more severe myocardial damage, and the high iron levels exacerbated myocardial I/R injury. However, the ferroptosis inhibitor Fer-1 significantly suppressed iron overload-induced ferroptosis and myocardial I/R injury. Moreover, Parkin effectively protected against impaired mitochondrial function and prevented iron overload-induced mitochondrial lipid peroxidation. These findings unveil a novel regulatory pathway involving p53-Parkin-ACSL4 in heart disease by inhibiting of ferroptosis.

BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo . Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p , and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p , miR-29a-3p , PIK3R1 , and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1 , PIK3R1 , and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS The POU2F1 - miR-29b-3p / miR-29a-3p-PIK3R1 / PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
MicroRNAs/metabolism* ; Humans ; Stomach Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement/physiology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Animals ; Mice ; Octamer Transcription Factor-1/metabolism* ; Mice, Nude ; Class Ia Phosphatidylinositol 3-Kinase/metabolism* ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic/genetics* ; Male ; Immunohistochemistry ; Female

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.