Currently, transcatheter intervention is the preferred treatment for patients with anatomically suitable atrial septal defects. However, the use of nickel-titanium alloy occluders in interventional procedures results in lifelong presence of the implant in the body, leading to complications such as metal allergies and arrhythmias in some patients. To overcome the short-term and long-term complications associated with the presence of metal, and to avoid radiation exposure and metal toxicity, this paper reports a case of successful transcatheter closure of atrial septal defect in a pediatric patient with metal allergies using fully biodegradable occluder under ultrasound guidance, achieving excellent results by interventional therapy.

Continuous manufacturing, as an innovative pharmaceutical production model, offers advantages such as high production efficiency and ease of control compared to traditional batch production, aligning with the future trend of drug production moving toward greater efficiency and intelligence. However, the development of continuous manufacturing technology in wet granulation has been slow. On one hand, this is closely related to its high technical complexity, substantial equipment investment costs, and stringent process control requirements. On the other hand, the long-term use of the traditional batch production model has created strong path dependence, and the lack of mature standardized processes further increases the difficulty of technological transformation. To promote the deep integration of wet granulation technology with continuous manufacturing, this review systematically outlines the current application of wet granulation in continuous manufacturing. It focuses on the development of key technologies such as online detection, process modeling, and process scale-up, with the aim of providing a reference for process innovation and application in wet granulation.
Drug Compounding/instrumentation* ; Technology, Pharmaceutical/methods* ; Drugs, Chinese Herbal/chemistry* ; Models, Theoretical

PURPOSE: Intertrochanteric fracture (ITF) classification is crucial for surgical decision-making. However, orthopedic trauma surgeons have shown lower accuracy in ITF classification than expected. The objective of this study was to utilize an artificial intelligence (AI) method to improve the accuracy of ITF classification. METHODS: We trained a network called YOLOX-SwinT, which is based on the You Only Look Once X (YOLOX) object detection network with Swin Transformer (SwinT) as the backbone architecture, using 762 radiographic ITF examinations as the training set. Subsequently, we recruited 5 senior orthopedic trauma surgeons (SOTS) and 5 junior orthopedic trauma surgeons (JOTS) to classify the 85 original images in the test set, as well as the images with the prediction results of the network model in sequence. Statistical analysis was performed using the SPSS 20.0 (IBM Corp., Armonk, NY, USA) to compare the differences among the SOTS, JOTS, SOTS + AI, JOTS + AI, SOTS + JOTS, and SOTS + JOTS + AI groups. All images were classified according to the AO/OTA 2018 classification system by 2 experienced trauma surgeons and verified by another expert in this field. Based on the actual clinical needs, after discussion, we integrated 8 subgroups into 5 new subgroups, and the dataset was divided into training, validation, and test sets by the ratio of 8:1:1. RESULTS: The mean average precision at the intersection over union (IoU) of 0.5 (mAP50) for subgroup detection reached 90.29%. The classification accuracy values of SOTS, JOTS, SOTS + AI, and JOTS + AI groups were 56.24% ± 4.02%, 35.29% ± 18.07%, 79.53% ± 7.14%, and 71.53% ± 5.22%, respectively. The paired t-test results showed that the difference between the SOTS and SOTS + AI groups was statistically significant, as well as the difference between the JOTS and JOTS + AI groups, and the SOTS + JOTS and SOTS + JOTS + AI groups. Moreover, the difference between the SOTS + JOTS and SOTS + JOTS + AI groups in each subgroup was statistically significant, with all p < 0.05. The independent samples t-test results showed that the difference between the SOTS and JOTS groups was statistically significant, while the difference between the SOTS + AI and JOTS + AI groups was not statistically significant. With the assistance of AI, the subgroup classification accuracy of both SOTS and JOTS was significantly improved, and JOTS achieved the same level as SOTS. CONCLUSION In conclusion, the YOLOX-SwinT network algorithm enhances the accuracy of AO/OTA subgroups classification of ITF by orthopedic trauma surgeons.
Humans ; Hip Fractures/diagnostic imaging* ; Orthopedic Surgeons ; Algorithms ; Artificial Intelligence

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

OBJECTIVE To statistically analyze and detect signals for the adverse drug reactions(ADRs)related to tigecycline based on the ADR spontaneous reporting system,so as to provide reference for the prevention of medi-cation risks of tigecycline.METHODS ADR reports of tigecycline were extracted from the ADR spontaneous repor-ting system of the hospital from Oct.2013 to Mar.2024.Statistical analysis was conducted by Microsoft Excel and Free Statistics 2.1.1.The data mining and analysis were performed using the reporting odds ratio(ROR),the proportional reporting ratio(PRR)and the composite criteria of UK Medicines and Healthcare products Regulato-ry Agency(MHRA).RESULTS Among the 574 ADR reports with tigecycline as the primarily suspected drug,elderly patients accounted for over 50％.The ADRs mainly occurred within one week after medication administra-tion,involving 12 organ systems and 57 adverse reaction signals.Through comprehensive analysis using three methods,20 positive risk signals related to tigecycline were identified,mainly affecting the gastrointestinal system,hepatobiliary system and hematological system.The top 5 frequent ADR signals were nausea,vomiting,diarrhea,thrombocytopenia and hyperbilirubinemia.According to the ROR method,the top five ranked ADR sig-nals were hyperbilirubinemia(ROR=330.55),hepatocellular injury(ROR=110.22),elevated amylase(ROR=78.90),cholestasis(ROR=73.32),and decreased fibrinogen(ROR=43.65).CONCLUSIONS The adverse reac-tions of tigecycline mainly occur during the initial stage of medication,and special caution is required when used in elderly patients.High-intensity risk signals for ADRs are hyperbilirubinemia,liver injury,and others related to hematological system and gastrointestinal system.Close monitoring of these ADRs and timely intervention are necessary during medication.

OBJECTIVE To statistically analyze and detect signals for the adverse drug reactions(ADRs)related to tigecycline based on the ADR spontaneous reporting system,so as to provide reference for the prevention of medi-cation risks of tigecycline.METHODS ADR reports of tigecycline were extracted from the ADR spontaneous repor-ting system of the hospital from Oct.2013 to Mar.2024.Statistical analysis was conducted by Microsoft Excel and Free Statistics 2.1.1.The data mining and analysis were performed using the reporting odds ratio(ROR),the proportional reporting ratio(PRR)and the composite criteria of UK Medicines and Healthcare products Regulato-ry Agency(MHRA).RESULTS Among the 574 ADR reports with tigecycline as the primarily suspected drug,elderly patients accounted for over 50％.The ADRs mainly occurred within one week after medication administra-tion,involving 12 organ systems and 57 adverse reaction signals.Through comprehensive analysis using three methods,20 positive risk signals related to tigecycline were identified,mainly affecting the gastrointestinal system,hepatobiliary system and hematological system.The top 5 frequent ADR signals were nausea,vomiting,diarrhea,thrombocytopenia and hyperbilirubinemia.According to the ROR method,the top five ranked ADR sig-nals were hyperbilirubinemia(ROR=330.55),hepatocellular injury(ROR=110.22),elevated amylase(ROR=78.90),cholestasis(ROR=73.32),and decreased fibrinogen(ROR=43.65).CONCLUSIONS The adverse reac-tions of tigecycline mainly occur during the initial stage of medication,and special caution is required when used in elderly patients.High-intensity risk signals for ADRs are hyperbilirubinemia,liver injury,and others related to hematological system and gastrointestinal system.Close monitoring of these ADRs and timely intervention are necessary during medication.

Interferon regulatory factor 4(IRF4)plays an important role in B-cell development and differentiation.Large B-cell lymphoma with IRF4 gene rearrangement(LBCL-IRF4)is a germinal center derived mature B-cell lym-phoma,initially classified as a special provisional type of follicular lymphoma.With advancing research and under-standing,LBCL-IRF4 has been shown to differ from classic follicular lymphoma(cFL),pediatric follicular lymphoma(PTFL)and diffuse large B-cell lymphoma(DLBCL).The latest fifth edition of the World Health Organization(WHO)classification of hematopoietic and lymphoid tissue tumors has officially classified this tumor as a distinct type under large B cell lymphoma.To gain a more comprehensive understanding of this tumor,this paper reviews the re-search progress on the clinicopathological and molecular genetic characteristics of LBCL-IRF4.

Interferon regulatory factor 4(IRF4)plays an important role in B-cell development and differentiation.Large B-cell lymphoma with IRF4 gene rearrangement(LBCL-IRF4)is a germinal center derived mature B-cell lym-phoma,initially classified as a special provisional type of follicular lymphoma.With advancing research and under-standing,LBCL-IRF4 has been shown to differ from classic follicular lymphoma(cFL),pediatric follicular lymphoma(PTFL)and diffuse large B-cell lymphoma(DLBCL).The latest fifth edition of the World Health Organization(WHO)classification of hematopoietic and lymphoid tissue tumors has officially classified this tumor as a distinct type under large B cell lymphoma.To gain a more comprehensive understanding of this tumor,this paper reviews the re-search progress on the clinicopathological and molecular genetic characteristics of LBCL-IRF4.

Objective To investigate the osteogenic properties of a methacrylated gelatin(GelMA)/bone marrow mesenchymal stem cells(BMSCs)composite hydrogel applied to the skull defect area of rats and to provide an experi-mental basis for the development of bone regeneration biomaterials.Methods This study was approved by the Animal Ethics Committee of Nanjing University.A novel photocurable composite biohydrogel was developed by constructing photoinitiators[lthium phenyl(2,4,6-trimethylbenzoyl)phosphinate,LAP],GelMA,and BMSCs.The surface morphology and elemental composition of the gel were examined using scanning electron microscopy(SEM)and energy-dispersive X-ray spectroscopy(EDX).The compressive strength of the gel was evaluated using an electronic universal testing ma-chine.After in vitro culture for 1,2,and 5 days,the proliferation of the BMSCs in the hydrogels was assessed using a CCK-8 assay,and their survival and morphology were examined through confocal microscopy.A 5 mm critical bone de-ficiency model was generated in a rat skull.The group receiving composite hydrogel treatment was referred to as the Gel-MA/BMSCs group,whereas the untreated group served as the control group.At the 4th and 8th weeks,micro-CT scans were taken to measure the bone defect area and new bone index,while at the 8th week,skull samples from the defect ar-ea were subjected to H&E staining,van Gieson staining,and Goldner staining to evaluate the quality of bone regenera-tion and new bone formation.Results SEM observed that the solidified GelMA showed a 3D spongy gel network with uniform morphology,the porosity of GelMA was 73.41％and the pore size of GelMA was(28.75±7.13)μm.EDX results showed that C and O were evenly distributed in the network macroporous structure of hydrogel.The hydrogel compres-sion strength was 152 kPa.On the 5th day of GelMA/BMSCs culture,the cellular morphology transitioned from oval to spindle shaped under microscopic observation,accompanied by a significant increase in cell proliferation(159.4％,as determined by the CCK-8 assay).At 4 weeks after surgery,a 3D reconstructed micro-CT image revealed a minimal re-duction in bone defect size within the control group and abundant new bone formation in the GelMA/BMSCs group.At 8 weeks after surgery,no significant changes were observed in the control group's bone defect area,with only limited evi-dence of new bone growth;however,substantial healing of skull defects was evident in the GelMA/BMSCs group.Quan-titative analysis at both the 4-and 8-week examinations indicated significant improvements in the new bone volume(BV),new bone volume/total bone volume(BV/TV),bone surface(BS),and bone surface/total bone volume(BS/TV)in the GelMA/BMSCs group compared to those in the control group(P＜0.05).Histological staining showed continuous and dense formation of bone tissue within the defects in the GelMA/BMSCs group and only sporadic formation of new bone,primarily consisting of fibrous connective tissue,at the defect edge in the control group.Conclusion Photocur-ing hydrogel-based stem cell therapy exhibits favorable biosafety profiles and has potential for clinical application by inducing new bone formation and promoting maturation within rat skull defects.

Non-communicable diseases(NCDs),including cardiovascular diseases,cancer,metabolic diseases,and skeletal diseases,pose significant challenges to public health worldwide.The complex pathogenesis of these diseases is closely linked to oxidative stress and inflammatory damage.Nuclear factor erythroid 2-related factor 2(Nrf2),a critical transcription factor,plays an important role in regulating antioxidant and anti-inflammatory responses to protect the cells from oxidative damage and inflammation-mediated injury.Therefore,Nrf2-targeting therapies hold promise for preventing and treating NCDs.Quercetin(Que)is a widely available flavonoid that has significant antioxidant and anti-inflammatory properties.It modulates the Nrf2 signaling pathway to ameliorate oxidative stress and inflammation.Que modulates mitochondrial function,apoptosis,autophagy,and cell damage biomarkers to regulate oxidative stress and inflammation,highlighting its efficacy as a therapeutic agent against NCDs.Here,we discussed,for the first time,the close association between NCD pathogenesis and the Nrf2 signaling pathway,involved in neurodegenerative diseases(NDDs),cardiovascular disease,cancers,organ damage,and bone damage.Furthermore,we reviewed the availability,pharmacokinetics,pharmaceutics,and therapeutic applica-tions of Que in treating NCDs.In addition,we focused on the challenges and prospects for its clinical use.Que represents a promising candidate for the treatment of NCDs due to its Nrf2-targeting properties.