Synthetic approaches and clinical application of representative small-molecule inhibitors of phosphodiesterase.

Phosphodiesterases (PDEs) constitute a family of enzymes that play a pivotal role in the regulation of intracellular levels of cyclic nucleotides, including cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Dysregulation of PDE activity has been implicated in diverse pathological conditions encompassing cardiovascular disorders, pulmonary diseases, and neurological disorders. Small-molecule inhibitors targeting PDEs have emerged as promising therapeutic agents for the treatment of these ailments, some of which have been approved for their clinical use. Despite their success, challenges such as resistance mechanisms and off-target effects persist, urging continuous research for the development of next-generation PDE inhibitors. The objective of this review is to provide an overview of the synthesis and clinical application of representative approved small-molecule PDE inhibitors, with the aim of offering guidance for further advancements in the development of novel PDE inhibitors.

Synthetic routes and clinical application of new drugs approved by EMA during 2023.

In 2023, the European Medicines Agency (EMA) granted approval to 77 new molecular entities (NMEs), consisting of 45 new chemical entities (NCEs) and 32 new biological entities (NBEs). These pharmacological agents encompass a broad spectrum of therapeutic domains, including oncology, cardiology, dermatology, diagnostic medicine, endocrinology, gastroenterology and hepatology, metabolic disorders, and neurology. Among the 77 approved pharmaceuticals, three received accelerated review status, and 17 (22 %) were granted orphan drug designation for the treatment of rare diseases. This review provides an overview of the clinical applications and synthetic routes of 42 newly approved NCEs by the EMA in 2023. The objective is to offer a comprehensive understanding of the synthetic approaches used in the development of these drug molecules, thereby inspiring the creation of novel, efficient, and applicable synthetic methodologies.

Investigation into the potential mechanism and therapeutic targets of Cangzhu Erchen decoction for the treatment of chronic obstructive pulmonary disease based on bioinformatics and network pharmacology.

This study aimed to elucidate the molecular mechanisms underlying the therapeutic effects of Cangzhu Erchen decoction (CZECD) in the treatment of chronic obstructive pulmonary disease (COPD) using microarray analysis, network pharmacology, and molecular docking. The active components and candidate targets of CZECD were obtained using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Swiss Target Prediction. COPD-related targets were collected from 5 databases. Access to drug-disease interface targets in the Venny platform. The Cytoscape program and the STRING database were used for protein-protein interaction analysis and subsequent core target screening. The DAVID database was used for Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes enrichment pathway analysis, while AutoDockTools was used for molecular docking to confirm binding affinity between drugs and key targets. A total of 140 compounds from CZECD and 5100 COPD-related targets were identified. SRC, PIK3CA, STAT3, PIK3R1, AKT1, HSP90AA1, PIK3CB, GRB2, PIK3CD, and MAPK1 were identified as the major targets of CZECD in its anti-COPD activity. GO and Kyoto Encyclopedia of Genes and Genomes enrichment studies revealed that CZECD mainly affects biological processes such as protein phosphorylation, xenobiotic response, positive regulation of the MAPK cascade, and inflammatory responses. Cancer, PI3K/AKT, and MAPK were the key pathways mediating these effects. The positive association between the core targets and the compounds was further validated by molecular docking. CZECD exerts its therapeutic role in COPD mainly through multiple compounds, targets, and pathways.

From lab to clinic: The discovery and optimization journey of PI3K inhibitors.

PI3K inhibitors have emerged as promising therapeutic agents due to their critical role in various cellular processes, particularly in cancer, where the PI3K pathway is frequently dysregulated. This review explores the evolutionary path of PI3K inhibitors from laboratory discovery to clinical application. The journey begins with early laboratory investigations into PI3K signaling and inhibitor development, highlighting fundamental discoveries that laid the foundation for subsequent advancements. Optimization strategies, including medicinal chemistry approaches and structural modifications, are scrutinized for their contributions to enhancing inhibitor potency, selectivity, and pharmacokinetic properties. The translation from preclinical studies to clinical trials is examined, emphasizing pivotal trials that evaluated efficacy and safety profiles. Challenges encountered during clinical development are critically assessed. Finally, the review discusses ongoing research directions and prospects for PI3K inhibitors, underscoring these agents' continuous evolution and therapeutic potential.

Tannic acid coating gauze immobilized with thrombin with ultra-high coagulation activity and antimicrobial property for uncontrollable hemorrhage.

Rapid and safe hemostasis is crucial for the survival of bleeding patients in prehospital care. It is urgent to develop high performance hemostatic material to control the massive hemorrhage in the military field and accidental trauma. In this work, an efficient protein hemostat of thrombin was immobilized onto commercial gauze, which was mediated by self-polymerization and anchoring of tannic acid (TA). Through TA treatment, the efficient immobilization of thrombin was achieved, preserving both the biological activity of thrombin and the physical properties of the dressing, including absorbency, breathability, and mechanical performance. Moreover, in the presence of TA coating and thrombin, Gau@TA/Thr could obviously shortened clotting time and enriched blood components such as plasma proteins, platelets, and red blood cells, thereby exhibiting an enhanced in vitro coagulation effect. In SD rat liver volume defect and artery transection hemorrhage models, Gau@TA/Thr still had outstanding hemostatic performance. Besides, the Gau@TA/Thr gauze had inherent antibacterial property and demonstrated excellent biocompatibility. All results suggested that Gau@TA/Thr would be a potential candidate for treating uncontrollable hemorrhage in prehospital care.

Segmentation Guided Crossing Dual Decoding Generative Adversarial Network for Synthesizing Contrast-Enhanced Computed Tomography Images.

Although contrast-enhanced computed tomography (CE-CT) images significantly improve the accuracy of diagnosing focal liver lesions (FLLs), the administration of contrast agents imposes a considerable physical burden on patients. The utilization of generative models to synthesize CE-CT images from non-contrasted CT images offers a promising solution. However, existing image synthesis models tend to overlook the importance of critical regions, inevitably reducing their effectiveness in downstream tasks. To overcome this challenge, we propose an innovative CE-CT image synthesis model called Segmentation Guided Crossing Dual Decoding Generative Adversarial Network (SGCDD-GAN). Specifically, the SGCDD-GAN involves a crossing dual decoding generator including an attention decoder and an improved transformation decoder. The attention decoder is designed to highlight some critical regions within the abdominal cavity, while the improved transformation decoder is responsible for synthesizing CE-CT images. These two decoders are interconnected using a crossing technique to enhance each other's capabilities. Furthermore, we employ a multi-task learning strategy to guide the generator to focus more on the lesion area. To evaluate the performance of proposed SGCDD-GAN, we test it on an in-house CE-CT dataset. In both CE-CT image synthesis tasks-namely, synthesizing ART images and synthesizing PV images-the proposed SGCDD-GAN demonstrates superior performance metrics across the entire image and liver region, including SSIM, PSNR, MSE, and PCC scores. Furthermore, CE-CT images synthetized from our SGCDD-GAN achieve remarkable accuracy rates of 82.68%, 94.11%, and 94.11% in a deep learning-based FLLs classification task, along with a pilot assessment conducted by two radiologists.

Interleukin-1 increases SERPINE1 expression in human granulosa-lutein cell via P50/P52 signaling pathways.

It has been reported that immune factors are associated with the occurrence of polycystic ovary syndrome (PCOS). Interleukin-1 (IL-1) is a member of the interleukin family that widely participates in the regulation of the inflammatory response in the immune system. In addition, it has been reported that aberrant IL-1 accumulation in serum is associated with the occurrence of PCOS. However, little is known about how IL-1 participates in the pathogenesis of PCOS. In the present study, we demonstrated that the immune microenvironment was altered in follicular fluid from PCOS patients and that the expression levels of two IL-1 cytokines, IL-1α and IL-1ß were increased. Transcriptome analysis revealed that IL-1α and IL-1ß treatment induced primary human granulosa-lutein (hGL) cell inflammatory response and increased the expression of serpin family E member 1 (SERPINE1). Mechanistically, we demonstrated that IL-1α and IL-1ß upregulated SERPINE1 expression through IL-1R1-mediated activation of downstream P50 and P52 signaling pathways in human granulosa cells. Our study highlighted the role of immune state changes in the occurrence of PCOS and provided new insight into the treatment of patients with IL-1-induced ovarian function disorders.

[Fire dragon cupping in prevention and treatment of chemotherapy-induced nausea and vomiting in breast cancer: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy and safety of fire dragon cupping in prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) in breast cancer. METHODS: Sixty breast cancer patients receiving medium-high emetogenic chemotherapy regimen were randomly divided into an observation group (30 cases, 3 cases dropped out) and a control group (30 cases, 3 cases dropped out). In both groups, 5 mg tropisetron hydrochloride was given intravenously on the day of chemotherapy and 1st to 3rd days after chemotherapy. In the observation group, fire dragon cupping on the abdomen was applied on 1st, 3rd and 5th days after chemotherapy. The incidence of nausea, vomiting, loss of appetite, abdominal pain, abdominal distension, the severity of nausea, vomiting on 1st to 6th days after chemotherapy, and the duration of nausea, vomiting, loss of appetite were observed in the two groups. The self-rating anxiety scale (SAS) score, general comfort questionnaire scale (GCQ) score before and after treatment and remedy antiemetic medication were observed in the two groups, and the safety was evaluated. RESULTS: On 2nd to 6th days after chemotherapy, the number of patients with nausea, loss of appetite and abdominal distension and nausea scores in the observation group were lower than those in the control group (P<0.05). On 1st to 3rd days after chemotherapy, the number of patients with vomiting and vomiting scores in the observation group were lower than those in the control group (P<0.05). The duration of nausea, vomiting and loss of appetite in the observation group were shorter than those in the control group (P<0.05). In the observation group, there was no significant difference in SAS and GCQ scores before and after treatment (P>0.05). After treatment, the GCQ score in the control group was decreased compared with that before treatment (P<0.05). After treatment, there was no significant difference in SAS and GCQ scores between the two groups (P>0.05). There was no significant difference in the number of patients using remedy medication between the two groups (P>0.05). No adverse reaction occurred during treatment in both groups. CONCLUSION: Fire dragon cupping can effectively reduce the incidence of nausea, vomiting, loss of appetite and the severity of nausea, vomiting related to chemotherapy in breast cancer, and improve patient comfort, and have good safety.

A novel fatty acid metabolism-related signature identifies MUC4 as a novel therapy target for esophageal squamous cell carcinoma.

Fatty acid metabolism has been identified as an emerging hallmark of cancer, which was closely associated with cancer prognosis. Whether fatty acid metabolism-related genes (FMGs) signature play a more crucial role in biological behavior of esophageal squamous cell carcinoma (ESCC) prognosis remains unknown. Thus, we aimed to identify a reliable FMGs signature for assisting treatment decisions and prognosis evaluation of ESCC. In the present study, we conducted consensus clustering analysis on 259 publicly available ESCC samples. The clinical information was downloaded from The Cancer Genome Atlas (TCGA, 80 ESCC samples) and Gene Expression Omnibus (GEO) database (GSE53625, 179 ESCC samples). A consensus clustering arithmetic was used to determine the FMGs molecular subtypes, and survival outcomes and immune features were evaluated among the different subtypes. Kaplan-Meier analysis and the receiver operating characteristic (ROC) was applied to evaluate the reliability of the risk model in training cohort, validation cohort and all cohorts. A nomogram to predict patients' 1-year, 3-year and 5-year survival rate was also studied. Finally, CCK-8 assay, wound healing assay, and transwell assay were implemented to evaluate the inherent mechanisms of FMGs for tumorigenesis in ESCC. Two subtypes were identified by consensus clustering, of which cluster 2 is preferentially associated with poor prognosis, lower immune cell infiltration. A fatty acid (FA) metabolism-related risk model containing eight genes (FZD10, TACSTD2, MUC4, PDLIM1, PRSS12, BAALC, DNAJA2 and ALOX12B) was established. High-risk group patients displayed worse survival, higher stromal, immune and ESTIMATE scores than in the low-risk group. Moreover, a nomogram revealed good predictive ability of clinical outcomes in ESCC patients. The results of qRT-PCR analysis revealed that the MUC4 and BAALC had high expression level, and FZD10, PDLIM1, TACSTD2, ALOX12B had low expression level in ESCC cells. In vitro, silencing MUC4 remarkably inhibited ESCC cell proliferation, invasion and migration. Our study fills the gap of FMGs signature in predicting the prognosis of ESCC patients. These findings revealed that cluster subtypes and risk model of FMGs had effects on survival prediction, and were expected to be the potential promising targets for ESCC.

MAP7 drives EMT and cisplatin resistance in ovarian cancer via wnt/ß-catenin signaling.

Methods: Our approach encompasses analyzing MAP7's expression levels across various datasets and clinical specimens, evaluating its association with patient outcomes, and probing its influence on ovarian cancer cell dynamics such as proliferation, migration, invasion, and apoptosis. Results: We have identified significant upregulation of MAP7 in ovarian cancer tissues, which correlates with advanced disease stages, higher pathological grades, and unfavorable prognoses. Functionally, the inhibition of MAP7 suppresses cancer cell proliferation, migration, and invasion while promoting apoptosis. Notably, the silencing of MAP7 attenuates the epithelial-mesenchymal transition (EMT) and disrupts Wnt/ß-catenin pathway signaling-two critical processes implicated in metastasis and chemoresistance. In cisplatin-resistant A2780-DDP cells, the downregulation of MAP7 effectively reverses their resistance to cisplatin. Furthermore, the nuclear localization of MAP7 in these cells underscores its pivotal role in driving cisplatin resistance by modulating the transcriptional regulation and interaction dynamics of ß-catenin. Conclusion: Our findings position MAP7 as a pivotal element in ovarian cancer advancement and cisplatin resistance, primarily through its modulation of EMT and the Wnt/ß-catenin pathway. Its association with poor clinical outcomes underscores its potential as both a prognostic marker and a therapeutic target. Strategies aimed at MAP7 could represent a new frontier in combating chemotherapy resistance in ovarian cancer, emphasizing its significance in crafting complementary treatments for this disease.

Multitask deep learning for prediction of microvascular invasion and recurrence-free survival in hepatocellular carcinoma based on MRI images.

BACKGROUND AND AIMS: Accurate preoperative prediction of microvascular invasion (MVI) and recurrence-free survival (RFS) is vital for personalised hepatocellular carcinoma (HCC) management. We developed a multitask deep learning model to predict MVI and RFS using preoperative MRI scans. METHODS: Utilising a retrospective dataset of 725 HCC patients from seven institutions, we developed and validated a multitask deep learning model focused on predicting MVI and RFS. The model employs a transformer architecture to extract critical features from preoperative MRI scans. It was trained on a set of 234 patients and internally validated on a set of 58 patients. External validation was performed using three independent sets (n = 212, 111, 110). RESULTS: The multitask deep learning model yielded high MVI prediction accuracy, with AUC values of 0.918 for the training set and 0.800 for the internal test set. In external test sets, AUC values were 0.837, 0.815 and 0.800. Radiologists' sensitivity and inter-rater agreement for MVI prediction improved significantly when integrated with the model. For RFS, the model achieved C-index values of 0.763 in the training set and ranged between 0.628 and 0.728 in external test sets. Notably, PA-TACE improved RFS only in patients predicted to have high MVI risk and low survival scores (p < .001). CONCLUSIONS: Our deep learning model allows accurate MVI and survival prediction in HCC patients. Prospective studies are warranted to assess the clinical utility of this model in guiding personalised treatment in conjunction with clinical criteria.

Imaging Features of Biliary Adenofibroma With Malignant Transformation: A Case Report and Literature Review.

Biliary adenofibroma (BAF) is a rare benign tumor, but it has the potential for malignant transformation. The differentiation between benign and malignant forms of BAF before surgery is of great importance for clinical decision-making. We report a case of BAF with invasive carcinoma. The patient did not present any clinical symptoms but had a history of hepatitis B virus infection for more than twenty years. Magnetic resonance imaging (MRI) revealed a solid and cystic 4 cm mass in segment II of the liver exhibiting hypointense signals on T1-weighted images and intermediate-to-high intensity signals on T2-weighted images. Enhancement scanning revealed markedly rim-like enhancement on the arterial phase, with the left inter-hepatic artery as the tumor-feeding artery, and wash-out on the venous and delayed phases. To the best of our knowledge, BAF with invasive carcinoma is uncommon. Preoperative qualitative diagnosis based on imaging features can achieve the maximum benefit for patients.

Histiocytic necrotizing lymphadenitis with hemophagocytic lymphohistiocytosis in adults: A single-center analysis of 5 cases.

BACKGROUND: Histiocytic necrotizing lymphadenitis (HNL) is a self-limited inflammatory disease of unknown pathogenesis. A very small fraction of patients with HNL could develop hemophagocytic lymphohistiocytosis (HLH), a hyperinflammatory disorder. These patients are diagnosed as HNL with HLH (HNL-HLH). HNL-HLH in the pediatric population has been systemically studied, however, the clinical, laboratory, and radiological features and outcomes of adult patients with HNL-HLH remain to be explored. We aimed to explore the clinical, laboratory, and radiological features and outcomes of adult patients with HNL-HLH. METHODS: We collected the clinical data of patients with HNL-HLH admitted to the First Affiliated Hospital of Nanjing Medical University from October 2010 to June 2015. All the patients underwent lymph node biopsy and have a pathological diagnosis of HNL. The age, gender, clinical presentation, lymph node signs, laboratory findings and imaging data, and pathological findings of the patients were collected. RESULTS: In this study, we reported five adult patients with HNL-HLH. All five patients showed enlarged lymph nodes and prolonged fever. Laboratory findings were consistent with the diagnosis of HLH. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) showed enlarged lymph nodes with increased FDG uptake and splenic hypermetabolism could be present. All the patients responded well to corticosteroids and had a good prognosis. Two of the five patients were diagnosed with systemic lupus erythematosus during the follow-up. CONCLUSIONS: Our study demonstrated that adult patients with HNL-HLH showed distinct clinical, laboratory, and radiological features. And the prognosis is good and patients could be managed with steroids and supportive care.

MSPA-DLA++: A Multi-Scale Phase Attention Deep Layer Aggregation for Lesion Detection in Multi-Phase CT Images.

Object detection using convolutional neural networks (CNNs) has achieved high performance and achieved state-of-the-art results with natural images. Compared to natural images, medical images present several challenges for lesion detection. First, the sizes of lesions vary tremendously, from several millimeters to several centimeters. Scale variations significantly affect lesion detection accuracy, especially for the detection of small lesions. Moreover, the effective extraction of temporal and spatial features from multi-phase CT images is also an important issue. In this paper, we propose a group-based deep layer aggregation method with multiphase attention for liver lesion detection in multi-phase CT images. The method, which is called MSPA-DLA++, is a backbone feature extraction network for anchor-free liver lesion detection in multi-phase CT images that addresses scale variations and extracts hidden features from such images. The effectiveness of the proposed method is demonstrated on public datasets (LiTS2017) and our private multiphase dataset. The results of the experiments show that MSPA-DLA++ can improve upon the performance of state-of-the-art networks by approximately 3.7%.

Ferroptosis: a new mechanism of traditional Chinese medicine for cancer treatment.

Ferroptosis, distinct from apoptosis, is a novel cellular death pathway characterized by the build-up of lipid peroxidation and reactive oxygen species (ROS) derived from lipids within cells. Recent studies demonstrated the efficacy of ferroptosis inducers in targeting malignant cells, thereby establishing a promising avenue for combating cancer. Traditional Chinese medicine (TCM) has a long history of use and is widely used in cancer treatment. TCM takes a holistic approach, viewing the patient as a system and utilizing herbal formulas to address complex diseases such as cancer. Recent TCM studies have elucidated the molecular mechanisms underlying ferroptosis induction during cancer treatment. These studies have identified numerous plant metabolites and derivatives that target multiple pathways and molecular targets. TCM can induce ferroptosis in tumor cells through various regulatory mechanisms, such as amino acid, iron, and lipid metabolism pathways, which may provide novel therapeutic strategies for apoptosis-resistant cancer treatment. TCM also influence anticancer immunotherapy via ferroptosis. This review comprehensively elucidates the molecular mechanisms underlying ferroptosis, highlights the pivotal regulatory genes involved in orchestrating this process, evaluates the advancements made in TCM research pertaining to ferroptosis, and provides theoretical insights into the induction of ferroptosis in tumors using botanical drugs.

Downregulation of homeobox A1 in human granulosa cells is involved in diminished ovarian reserve through promoting cell apoptosis and mitochondrial dysfunction.

Granulosa cell apoptosis contributes to the occurrence of diminished ovarian reserve (DOR). HOXA1, belonging to the HOX gene family, is involved in regulating cancer cell apoptosis. However, whether HOXA1 participates in the granulosa cell apoptosis in DOR patients remains to be elucidated. In the current study, we demonstrated the differential transcriptomic landscape of granulosa cells in DOR patients compared to that in the controls and identified decreased expression of the HOXA1 gene. Meanwhile, we found that HOXA1 was a gonadotropin-response gene, in which FSH could promote its expression, whereas LH inhibited HOXA1 expression in human granulosa cells. CCK-8 assay, flow cytometry and TUNEL staining results showed that inhibition of endogenous HOXA1 expression promoted human granulosa cell apoptosis. Moreover, knockdown of HOXA1 increased Bax while reducing Bcl2 protein expression. Furthermore, we found a total of 947 differentially expressed genes (DEGs), including 426 upregulated genes and 521 downregulated genes using transcriptome sequencing technology. Enrichment analysis results showed that the DEGs were involved in apoptosis and mitochondrial function-related signaling pathways. Knockdown of HOXA1 impaired mitochondrial functions, exhibiting increased reactive oxygen species (ROS) and cytoplasmic Ca2+ levels, decreased mitochondrial membrane potential, ATP production and mitochondrial DNA (mtDNA) copy number, and abnormal mitochondrial cristae. Our findings demonstrated that aberrantly reduced HOXA1 expression induced granulosa cell apoptosis in DOR patients and impaired mitochondrial function, which highlighted the potential role of HOXA1 in the occurrence of DOR and provided new insight for the treatment of DOR.

Natural isoflavone glabridin targets PI3Kγ as an adjuvant to increase the sensitivity of MDA-MB-231 to tamoxifen and DU145 to paclitaxel.

Glabridin is a natural isoflavone with estrogen receptor agonism and significant anti-tumor activity. Additionally, glabridin has a regulation effect on PI3K/AKT/mTOR pathway, but its exact target remains unclear. In this study, we evaluated the antitumor activity of glabridin against breast cancer and prostate cancer cells, and further clarified its targeting to PI3K. We found that glabridin could significantly inhibit the cell viability of human breast cancer and prostate cancer cell lines. It induced caspase activation cascade and cell apoptosis through decreasing the mitochondrial transmembrane potential and increasing the intracellular reactive oxygen species (ROS). Moreover, glabridin could attenuate epithelial-mesenchymal transition (EMT) progression by inhibiting cell migration. PharmMapper calculation showed that PI3Kγ might be the most potential target protein because of the highest Normal Fit score (0.9735) and z'-score (0.9797). Molecular docking and bio-layer interferometry (BLI) analysis further demonstrated the PI3Kγ targeting of glabridin. In vivo experiments showed that glabridin can effectively inhibit the tumor growth of breast cancer xenograft model, and does not show obvious hepatorenal toxicity. Moreover, glabridin could effectively promote the anti-proliferation and pro-apoptotic effects of tamoxifen on MDA-MB-231 cell and taxol on DU145 cell. Elucidating the targeting of glabridin to PI3K may lay a theoretical foundation for the structural derivatization of glabridin, which is expected to greatly promote the application and development of glabridin in the field of cancer therapy.

Deep Learning Radiomics Model of Dynamic Contrast-Enhanced MRI for Evaluating Vessels Encapsulating Tumor Clusters and Prognosis in Hepatocellular Carcinoma.

BACKGROUND: Vessels encapsulating tumor cluster (VETC) is a critical prognostic factor and therapeutic predictor of hepatocellular carcinoma (HCC). However, noninvasive evaluation of VETC remains challenging. PURPOSE: To develop and validate a deep learning radiomic (DLR) model of dynamic contrast-enhanced MRI (DCE-MRI) for the preoperative discrimination of VETC and prognosis of HCC. STUDY TYPE: Retrospective. POPULATION: A total of 221 patients with histologically confirmed HCC and stratified this cohort into training set (n = 154) and time-independent validation set (n = 67). FIELD STRENGTH/SEQUENCE: A 1.5 T and 3.0 T; DCE imaging with T1-weighted three-dimensional fast spoiled gradient echo. ASSESSMENT: Histological specimens were used to evaluate VETC status. VETC+ cases had a visible pattern (≥5% tumor area), while cases without any pattern were VETC-. The regions of intratumor and peritumor were segmented manually in the arterial, portal-venous and delayed phase (AP, PP, and DP, respectively) of DCE-MRI and reproducibility of segmentation was evaluated. Deep neural network and machine learning (ML) classifiers (logistic regression, decision tree, random forest, SVM, KNN, and Bayes) were used to develop nine DLR, 54 ML and clinical-radiological (CR) models based on AP, PP, and DP of DCE-MRI for evaluating VETC status and association with recurrence. STATISTICAL TESTS: The Fleiss kappa, intraclass correlation coefficient, receiver operating characteristic curve, area under the curve (AUC), Delong test and Kaplan-Meier survival analysis. P value <0.05 was considered as statistical significance. RESULTS: Pathological VETC+ were confirmed in 68 patients (training set: 46, validation set: 22). In the validation set, DLR model based on peritumor PP (peri-PP) phase had the best performance (AUC: 0.844) in comparison to CR (AUC: 0.591) and ML (AUC: 0.672) models. Significant differences in recurrence rates between peri-PP DLR model-predicted VETC+ and VETC- status were found. DATA CONCLUSIONS: The DLR model provides a noninvasive method to discriminate VETC status and prognosis of HCC patients preoperatively. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 2.

Effectiveness and safety analysis of titanium mesh grafting versus bone grafting in the treatment of spinal Tuberculosis: a systematic review and meta-analysis.

BACKGROUND: To systematically assess the safety and effectiveness of titanium mesh grafting compared with bone grafting in the treatment of spinal tuberculosis. METHODS: Electronic databases, including PubMed, Embase, Web of Science, and Cochrane Library, were searched from their inception until April 2023. The outcome indicators for patients treated with titanium mesh grafting or bone grafting for spinal tuberculosis include surgical duration, intraoperative blood loss, graft fusion time, American Spinal Injury Association (ASIA) Spinal Cord Injury Grade E assessment, VAS score, lumbar pain score, post-graft kyphotic angle, and postoperative complications. The Newcastle-Ottawa Scale (NOS) and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach were used for quality assessment and evidence grading of clinical studies. Funnel plots and Begg's test were employed for bias assessment. RESULTS: A total of 8 studies were finally included, comprising 523 patients, with 267 cases of titanium mesh fixation and 256 cases of bone grafting. The meta-analysis showed no significant statistical differences in surgical duration (Weighted Mean Difference (WMD) = -7.20, 95% Confidence Interval (CI): -28.06 to 13.67, P = 0.499), intraoperative blood loss (WMD = 16.22, 95% CI: -40.62 to 73.06, P = 0.576), graft fusion time (WMD = 0.97, 95% CI: -0.88 to 2.81, P = 0.304), ASIA Spinal Cord Injury Grade E assessment (Relative Risk (RR) = 1.03, 95% CI: 0.97 to 1.09, P = 0.346), and overall complications (RR = 0.87, 95% CI: 0.49 to 1.55, P = 0.643). Differences in VAS score, ODI lumbar pain score, and post-graft kyphotic angle between the titanium mesh grafting group and the bone grafting group were not significant within the 95% CI range. The rate of postoperative implant subsidence was slightly lower in bone grafting than in titanium mesh grafting (RR = 9.30, 95% CI: 1.05 to 82.22, P = 0.045). CONCLUSIONS: Both bone grafting and titanium mesh grafting are effective and safe for the surgery, with no significant statistical differences in the results. Considering the limitations of the present study, large-scale randomized controlled trials are warranted to further verify the reliability of this finding.