Deep learning-based multimodal image analysis predicts bone cement leakage during percutaneous kyphoplasty: protocol for model development, and validation by prospective and external datasets.

Background: Bone cement leakage (BCL) is one of the most prevalent complications of percutaneous kyphoplasty (PKP) for treating osteoporotic vertebral compression fracture (OVCF), which may result in severe secondary complications and poor outcomes. Previous studies employed several traditional machine learning (ML) models to predict BCL preoperatively, but effective and intelligent methods to bridge the distance between current models and real-life clinical applications remain lacking. Methods: We will develop a deep learning (DL)-based prediction model that directly analyzes preoperative computed tomography (CT) and magnetic resonance imaging (MRI) of patients with OVCF to accurately predict BCL occurrence and classification during PKP. This retrospective study includes a retrospective internal dataset for DL model training and validation, a prospective internal dataset, and a cross-center external dataset for model testing. We will evaluate not only model's predictive performance, but also its reliability by calculating its consistency with reference standards and comparing it with that of clinician prediction. Discussion: The model holds an imperative clinical significance. Clinicians can formulate more targeted treatment strategies to minimize the incidence of BCL, thereby improving clinical outcomes by preoperatively identifying patients at high risk for each BCL subtype. In particular, the model holds great potential to be extended and applied in remote areas where medical resources are relatively scarce so that more patients can benefit from quality perioperative evaluation and management strategies. Moreover, the model will efficiently promote information sharing and decision-making between clinicians and patients, thereby increasing the overall quality of healthcare services.

Chinese Public Attitudes and Opinions on Health Policies During Public Health Emergencies: Sentiment and Topic Analysis.

BACKGROUND: By the end of 2021, the new wave of COVID-19 sparked by the Omicron variant spread rapidly due to its highly contagious nature, affecting more than 170 countries worldwide. Nucleic acid testing became the gold standard for diagnosing novel coronavirus infections. As of July 2022, numerous cities and regions in China have implemented regular nucleic acid testing policies, which have had a significant impact on socioeconomics and people's lives. This policy has garnered widespread attention on social media platforms. OBJECTIVE: This study took the newly issued regular nucleic acid testing policy during the COVID-19 pandemic as an example to explore the sentiment responses and fluctuations of netizens toward new policies during public health emergencies. It aimed to propose strategies for managing public opinion on the internet and provide recommendations for policy making and public opinion control. METHODS: We collected blog posts related to nucleic acid testing on Weibo from April 1, 2022, to July 31, 2022. We used the topic modeling technique latent Dirichlet allocation (LDA) to identify the most common topics posted by users. We used Bidirectional Encoder Representations from Transformers (BERT) to calculate the sentiment score of each post. We used an autoregressive integrated moving average (ARIMA) model to examine the relationship between sentiment scores and changes over time. We compared the differences in sentiment scores across various topics, as well as the changes in sentiment before and after the announcement of the nucleic acid price reduction policy (May 22) and the lifting of the lockdown policy in Shanghai (June 1). RESULTS: We collected a total of 463,566 Weibo posts, with an average of 3799.72 (SD 1296.06) posts published daily. The LDA topic extraction identified 8 topics, with the most numerous being the Shanghai outbreak, nucleic acid testing price, and transportation. The average sentiment score of the posts was 0.64 (SD 0.31), indicating a predominance of positive sentiment. For all topics, posts with positive sentiment consistently outnumbered those with negative sentiment (χ27=24,844.4, P<.001). The sentiment scores of posts related to "nucleic acid testing price" decreased after May 22 compared with before (t120=3.882, P<.001). Similarly, the sentiment scores of posts related to the "Shanghai outbreak" decreased after June 1 compared with before (t120=11.943, P<.001). CONCLUSIONS: During public health emergencies, the topics of public concern were diverse. Public sentiment toward the regular nucleic acid testing policy was generally positive, but fluctuations occurred following the announcement of key policies. To understand the primary concerns of the public, the government needs to monitor social media posts by citizens. By promptly sharing information on media platforms and engaging in effective communication, the government can bridge the information gap between the public and government agencies, fostering a positive public opinion environment.

Prostate cancer microenvironment: multidimensional regulation of immune cells, vascular system, stromal cells, and microbiota.

BACKGROUND: Prostate cancer (PCa) is one of the most prevalent malignancies in males worldwide. Increasing research attention has focused on the PCa microenvironment, which plays a crucial role in tumor progression and therapy resistance. This review aims to provide a comprehensive overview of the key components of the PCa microenvironment, including immune cells, vascular systems, stromal cells, and microbiota, and explore their implications for diagnosis and treatment. METHODS: Keywords such as "prostate cancer", "tumor microenvironment", "immune cells", "vascular system", "stromal cells", and "microbiota" were used for literature retrieval through online databases including PubMed and Web of Science. Studies related to the PCa microenvironment were selected, with a particular focus on those discussing the roles of immune cells, vascular systems, stromal cells, and microbiota in the development, progression, and treatment of PCa. The selection criteria prioritized peer-reviewed articles published in the last five years, aiming to summarize and analyze the latest research advancements and clinical relevance regarding the PCa microenvironment. RESULTS: The PCa microenvironment is highly complex and dynamic, with immune cells contributing to immunosuppressive conditions, stromal cells promoting tumor growth, and microbiota potentially affecting androgen metabolism. Vascular systems support angiogenesis, which fosters tumor expansion. Understanding these components offers insight into the mechanisms driving PCa progression and opens avenues for novel therapeutic strategies targeting the tumor microenvironment. CONCLUSIONS: A deeper understanding of the PCa microenvironment is crucial for advancing diagnostic techniques and developing precision therapies. This review highlights the potential of targeting the microenvironment to improve patient outcomes, emphasizing its significance in the broader context of PCa research and treatment innovation.

CYP1B1 promotes PARPi-resistance via histone H1.4 interaction and increased chromatin accessibility in ovarian cancer.

INTRODUCTION: Ovarian cancer is the most lethal gynecological cancer and presents significant therapeutic challenges. The discovery of synthetic lethality between PARP inhibitors (PARPi) and homologous recombination deficiency marked a new era in treating BRCA1/2-mutated tumors. However, PARPi resistance remains a major clinical challenge. METHODS: RNA sequencing was used to identify genes altered by PARPi treatment and LC-MS was used to detect proteins interacting with CYP1B1. Resistance mechanisms were explored through ATAC-seq and gene expression manipulation. Additional techniques, including micrococcal nuclease digestion assays, DAPI staining, and fluorescence microscopy, were used to assess changes in nuclear morphology and chromatin accessibility. RESULTS: The gradual exposure of Olaparib has developed a PARPi-resistant cell line, A2780-OlaR, which exhibits significant upregulation of CYP1B1 at both RNA and protein levels. Down-regulating CYP1B1 expression or using specific inhibitors decreased the cellular response to Olaparib. Linker histone H1.4 was identified as associated with CYP1B1. ATAC-seq showed differential chromatin accessibility between A2780-OlaR and parental cells, indicating that the downregulation of H1.4 was associated with increased chromatin accessibility and higher cell viability after Olaparib treatment. CONCLUSION: Our findings reveal a novel role for CYP1B1 in driving PARPi resistance through distinct molecular mechanisms in A2780-OlaR. This study highlights the importance of chromatin accessibility in PARPi efficacy and suggests the CYP1B1/H1.4 axis as a promising therapeutic target for overcoming drug resistance in ovarian cancer, offering potentially therapeutic benefits.

Clinical outcomes of percutaneous transforaminal endoscopic decompression for the treatment of degenerative lumbar scoliosis associated with spinal stenosis in elderly individuals: a matched comparison study.

PURPOSE: This retrospective cohort study evaluated the efficacy and safety of percutaneous transforaminal endoscopic decompression (PTED) in elderly patients with degenerative lumbar scoliosis (DLS) associated with lumbar spinal stenosis (LSS). STUDY DESIGN: A matched comparison study. METHODS: In total, 97 patients with DLS associated with LSS who underwent PTED under local anesthesia between 2016 and 2021 were retrospectively analyzed. Using the inclusion and exclusion criteria, 24 patients aged ≥ 80 years were screened and included in the study group. Then, 24 patients aged 50-80 years were matched according to gender, date of surgery, and surgical levels were included in the control group. Clinical outcomes such as the visual analog scale (VAS) score, Oswestry Disability Index (ODI) score, modified MacNab criteria, radiological parameters, and complications were assessed. The independent sample t-test, Pearson's chi-square test and Fisher's exact test were used to compare the parameters between the study and control groups. RESULTS: The study group had significantly higher mean American Society of Anesthesiologists classification and age-adjusted Charlson Comorbidity Index scores than the control group (2.42 ± 0.72) vs. 5.25 ± 1.03 and 1.67 ± 0.76 vs. 3.17 ± 2.10, respectively). The VAS scores for pain in two legs and back and ODI scores significantly improved at two weeks after surgery and at the final followup (p < 0.05). The study group had higher back pain VAS and ODI scores than the control group at the final followup (p < 0.05). In addition, the complication and patient satisfaction rates were similar between the two groups (p > 0.05). The overall radiological parameters were comparable between the two groups, and there was no significant deterioration in coronal imbalance or loss of disc height between the two groups. CONCLUSION: Elderly patients (aged ≥ 80 years) with DLS associated with LSS are less fit and have a greater number of comorbidities. However, they can achieve satisfactory outcomes with PTED, which are comparable to those of patients < 80 years. PTED under local anesthesia can also be an efficient alternative to conventional open lumbar decompression surgery for treating elderly patients with comorbidities.

Ethanol extract of Vanilla planifolia stems reduces PAK6 expression and induces cell death in glioblastoma cells.

Glioblastoma multiforme (GBM) is a malignant tumour with a poor prognosis. Therefore, potential treatment strategies and novel therapeutic targets have gained increased attention. Our data showed that the ethanol extract of Vanilla planifolia stem (VAS) significantly decreased the viability and the colony formation of GBM cells. Moreover, VAS induced the cleavage of MAP1LC3, a marker of autophagy. Further RNA-seq and bioinformatic analysis revealed 4248 differentially expressed genes (DEGs) between VAS-treated GBM cells and the control cells. Protein-protein interactions between DEGs with fold changes less than -3 and more than 5 were further analysed, and we found that 16 and 9 hub DEGs, respectively, were correlated with other DEGs. Further qPCR experiments confirmed that 14 hub DEGs was significantly downregulated and 9 hub DEGs was significantly upregulated. In addition, another significantly downregulated DEG, p21-activated kinase 6 (PAK6), was correlated with the overall survival of GBM patients. Further validation experiments confirmed that VAS significantly reduced the mRNA and protein expression of PAK6, which led to the abolition of cell viability and colony formation. These findings demonstrated that VAS reduced cell viability, suppressed colony formation and induced autophagy and revealed PAK6 and other DEGs as potential therapeutic targets for GBM treatment.

Efficacy of selenium supplementation for patients with Graves' hyperthyroidism during methimazole treatment: protocol for a systematic review and meta-analysis.

INTRODUCTION: The most common cause of hyperthyroidism, Graves' disease is a common organ-specific autoimmune disease. Selenium is an essential trace element of the human body that is mainly concentrated in the thyroid gland and is involved in the synthesis and metabolism of thyroid hormones. Most studies have shown that the level of selenium is closely related to the occurrence and development of thyroid diseases, and selenium supplementation can help improve thyroid function. This study aims to evaluate the efficacy of selenium supplementation for patients with Graves' hyperthyroidism during methimazole treatment. METHODS AND ANALYSIS: We will search the electronic databases including PubMed, Web of Science, Embase, the Cochrane Library, China National Knowledge Infrastructure, Wanfang Data and Chinese Biomedical Literature, and the time was deadline to December 2023. To evaluate the efficacy of methimazole combined with selenium supplementation in the treatment of Graves' hyperthyroidism, randomised controlled trials will be included. The Cochrane Collaboration's risk of bias tool will be used to assess the quality of all included studies, and the baseline data of all the studies are extracted by the authors. A random-effects model or a fixed-effects model is used to analyse the outcomes. The primary outcomes are the levels of selenium, triiodothyronine, free thyroxine and thyroid-stimulating hormone (TSH), whereas the secondary outcomes include TSH receptor antibody, thyroid peroxidase antibody and thyroglobulin antibody. ETHICS AND DISSEMINATION: Ethics approval is not required since no original data will be collected. The results of this study will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023410999.

The mechanism of action and chemical synthesis of FDA newly approved drug molecules.

In 2023, the U.S. Food and Drug Administration has approved 29 small molecule drugs. These newly approved small molecule drugs possess the distinct scaffolds, thereby exhibiting diverse mechanisms of action and binding modalities. Moreover, the marketed drugs have always been an important source of new drug development and creative inspiration, thereby fostering analogous endeavors in drug discovery that potentially extend to the diverse clinical indications. Therefore, conducting a comprehensive evaluation of drug approval experience and associated information will facilitate the expedited identification of highly potent drug molecules. In this review, we comprehensively summarized the relevant information regarding the clinical applications, mechanisms of action and chemical synthesis of 29 small molecule drugs, with the aim of providing a promising structural basis and design inspiration for pharmaceutical chemists.

Effects of AI-2 quorum sensing related luxS gene on Streptococcus suis formatting monosaccharide metabolism-dependent biofilm.

Biofilm is the primary cause of persistent infections caused by Streptococcus suis (S. suis). Metabolism and AI-2 quorum sensing are intricately linked to S. suis biofilm formation. Although the role of the AI-2 quorum sensing luxS gene in S. suis biofilm has been reported, its specific regulatory mechanism remains unclear. This study explored the differences in biofilm formation and monosaccharide metabolism among the wild type (WT), luxS mutant (ΔluxS) and complement strain (CΔluxS), and Galleria mellonella larvae were used to access the effect of luxS gene deletion on the virulence of S. suis in different monosaccharide medias. The results indicated that deletion of the luxS gene further compromised the monosaccharide metabolism of S. suis, impacting its growth in media with fructose, galactose, rhamnose, and mannose as the sole carbon sources. However, no significant impact was observed in media with glucose and N-acetylglucosamine. This deletion also weakened EPS synthesis, thereby diminishing the biofilm formation capacity of S. suis. Additionally, the downregulation of adhesion gene expression due to luxS gene deletion was found to be independent of the monosaccharide medias of S. suis.

Natural Products on Inflammatory Bowel Disease: Role of Gut Microbes.

Inflammatory bowel disease (IBD) refers to long-term medical conditions that involve inflammation of the digestive tract, and the global incidence and prevalence of IBD are on the rise. Gut microbes play an important role in maintaining the intestinal health of the host, and the occurrence, development, and therapeutic effects of IBD are closely related to the structural and functional changes of gut microbes. Published studies have shown that the natural products from traditional Chinese medicine have direct or indirect regulatory impacts on the composition and metabolism of the gut microbes. In this review, we summarize the research progress of several groups of natural products, i.e., flavonoids, alkaloids, saponins, polysaccharides, polyphenols, and terpenoids, for the therapeutic activities in relieving IBD symptoms. The role of gut microbes and their intestinal metabolites in managing the IBD is presented, with focusing on the mechanism of action of those natural products. Traditional Chinese medicine alleviated IBD symptoms by regulating gut microbes, providing important theoretical and practical basis for the treatment of variable inflammatory intestinal diseases.

A comprehensive review of new small molecule drugs approved by the FDA in 2022: Advance and prospect.

In 2022, the U.S. Food and Drug Administration approved a total of 16 marketing applications for small molecule drugs, which not only provided dominant scaffolds but also introduced novel mechanisms of action and clinical indications. The successful cases provide valuable information for optimizing efficacy and enhancing pharmacokinetic properties through strategies like macrocyclization, bioequivalent group utilization, prodrug synthesis, and conformation restriction. Therefore, gaining an in-depth understanding of the design principles and strategies underlying these drugs will greatly facilitate the development of new therapeutic agents. This review focuses on the research and development process of these newly approved small molecule drugs including drug design, structural modification, and improvement of pharmacokinetic properties to inspire future research in this field.

Discovery of novel pyrazolo[1,5-a]pyrimidine derivatives as potent reversal agents against ABCB1-mediated multidrug resistance.

The P-glycoprotein (ABCB1)-mediated multidrug resistance (MDR) has emerged as a significant impediment to the efficacy of cancer chemotherapy in clinical therapy, which could promote the development of effective agents for MDR reversal. In this work, we reported the exploration of novel pyrazolo [1,5-a]pyrimidine derivatives as potent reversal agents capable of enhancing the sensitivity of ABCB1-mediated MDR MCF-7/ADR cells to paclitaxel (PTX). Among them, compound 16q remarkably increased the sensitivity of MCF-7/ADR cells to PTX at 5 µM (IC50 = 27.00 nM, RF = 247.40) and 10 µM (IC50 = 10.07 nM, RF = 663.44). Compound 16q could effectively bind and stabilize ABCB1, and does not affect the expression and subcellular localization of ABCB1 in MCF-7/ADR cells. Compound 16q inhibited the function of ABCB1, thereby increasing PTX accumulation, and interrupting the accumulation and efflux of the ABCB1-mediated Rh123, thus resulting in exhibiting good reversal effects. In addition, due to the potent reversal effects of compound 16q, the abilities of PTX to inhibit tubulin depolymerization, and induce cell cycle arrest and apoptosis in MCF-7/ADR cells under low-dose conditions were restored. These results indicate that compound 16q might be a promising potent reversal agent capable of revising ABCB1-mediated MDR, and pyrazolo [1,5-a]pyrimidine might represent a novel scaffold for the discovery of new ABCB1-mediated MDR reversal agents.

Deep learning assisted segmentation of the lumbar intervertebral disc: a systematic review and meta-analysis.

BACKGROUND: In recent years, deep learning (DL) technology has been increasingly used for the diagnosis and treatment of lumbar intervertebral disc (IVD) degeneration. This study aims to evaluate the performance of DL technology for IVD segmentation in magnetic resonance (MR) images and explore improvement strategies. METHODS: We developed a PRISMA systematic review protocol and systematically reviewed studies that used DL algorithm frameworks to perform IVD segmentation based on MR images published up to April 10, 2024. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess methodological quality, and the pooled dice similarity coefficient (DSC) score and Intersection over Union (IoU) were calculated to evaluate segmentation performance. RESULTS: 45 studies were included in this systematic review, of which 16 provided complete segmentation performance data and were included in the quantitative meta-analysis. The results indicated that DL models showed satisfactory IVD segmentation performance, with a pooled DSC of 0.900 (95% confidence interval [CI]: 0.887-0.914) and IoU of 0.863 (95% CI: 0.730-0.995). However, the subgroup analysis did not show significant effects of factors on IVD segmentation performance, including network dimensionality, algorithm type, publication year, number of patients, scanning direction, data augmentation, and cross-validation. CONCLUSIONS: This study highlights the potential of DL technology in IVD segmentation and its further applications. However, due to the heterogeneity in algorithm frameworks and result reporting of the included studies, the conclusions should be interpreted with caution. Future research should focus on training generalized models on large-scale datasets to enhance their clinical application.

Shikonin from lithospermum erythrorhizon induces pyroptosis in trophoblast cells by activating the CTSB-NLRP3 inflammasome.

BACKGROUND: With the decline of global fertility, drug therapeutic of ectopic pregnancy is of great significance. Lithospermum erythrorhizon is using for embryo killing as herbal medicine. Shikonin is the critical nucleus of Lithospermum erythrorhizon; however, the mechanism is still unclear. The study aimed to explore the mechanism of shikonin against ectopic pregnancy. MATERIAL AND METHODS: In this study, we examined the viability and LDH release of HTR-8/SVneo cells by assays, observed pore formation in cell membranes by microscopy imaging and PI staining, and IL-1ß release by WB and ELISA assay kit. Then, we used network pharmacology to analyse the potential interaction between shikonin, ectopic pregnancy and pyroptosis and used molecular docking techniques to verify interactions between shikonin and core common targets. Finally, western blotting and immunofluorescence assay were used to explore the mechanism of shikonin-inducing pyroptosis of HTR-8/SVneo cells. RESULTS: Shikonin could cause a significant inhibition of HTR-8/SVneo cell viability in a concentration- and time-dependent manner. In HTR-8/SVneo cells, shikonin-induced cell swelling, bubble formation, an increase in the release of lactate dehydrogenase (LDH) and up-regulation of several pyroptosis-associated factors. And network pharmacology showed that The main targets of shikonin-ectopic pregnancy-pyroptosis were IL-1ß and caspase-1, and molecular docking results showed that shikonin can closely bind to IL-1ß, caspase-1 and GSDMD. Additionally, the necroptosis inhibitor GSK'872 could not suppress the expression of mature-IL-1ß and prevent the pyroptosis phenotype from developing. However, the nucleotide oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inhibitor MCC-950 could downregulate the expression of pyroptosis-associated factors and prevent the pyroptosis phenotype from developing. Shikonin led to an elevation in the expression of cathepsin B (CTSB), and the CTSB inhibitor CA-074 abolished pyroptosis induced by shikonin; however, the NLRP3 inhibitor MCC-950 could not inhibit the expression of CTSB. CONCLUSIONS: Our results suggest that shikonin activates CTSB to induce NLRP3-dependent pyroptosis in HTR-8/SVneo cells. This study has important clinical implications for the treatment of ectopic pregnancy.

Discovery of 1,2,4-Triazole-3-thione Derivatives as Potent and Selective DCN1 Inhibitors for Pathological Cardiac Fibrosis and Remodeling.

DCN1, a critical co-E3 ligase during the neddylation process, is overactivated in many diseases, such as cancers, heart failure as well as fibrotic diseases, and has been regarded as a new target for drug development. Herein, we designed and synthesized a new class of 1,2,4-triazole-3-thione-based DCN1 inhibitors based the hit HD1 identified from high-throughput screening and optimized through numerous structure-activity-relationship (SAR) explorations. HD2 (IC50= 2.96 nM) was finally identified and represented a highly potent and selective DCN1 inhibitor with favorable PK properties and low toxicity. Amazingly, HD2 effectively relieved Ang II/TGFß-induced cardiac fibroblast activation in vitro, and reduced ISO-induced cardiac fibrosis as well as remodeling in vivo, which was linked to the inhibition of cullin 3 neddylation and its substrate Nrf2 accumulation. Our findings unveil a novel 1,2,4-triazole-3-thione-based derivative HD2, which can be recognized as a promising lead compound targeting DCN1 for cardiac fibrosis and remodeling.

The recent advance and prospect of poly(ADP-ribose) polymerase inhibitors for the treatment of cancer.

Chemotherapies are commonly used in cancer therapy, their applications are limited to low specificity, severe adverse reactions, and long-term medication-induced drug resistance. Poly(ADP-ribose) polymerase (PARP) inhibitors are a novel class of antitumor drugs developed to solve these intractable problems based on the mechanism of DNA damage repair, which have been widely applied in the treatment of ovarian cancer, breast cancer, and other cancers through inducing synthetic lethal effect and trapping PARP-DNA complex in BRCA gene mutated cancer cells. In recent years, PARP inhibitors have been widely used in combination with various first-line chemotherapy drugs, targeted drugs and immune checkpoint inhibitors to expand the scope of clinical application. However, the intricate mechanisms underlying the drug resistance to PARP inhibitors, including the restoration of homologous recombination, stabilization of DNA replication forks, overexpression of drug efflux protein, and epigenetic modifications pose great challenges and desirability in the development of novel PARP inhibitors. In this review, we will focus on the mechanism, structure-activity relationship, and multidrug resistance associated with the representative PARP inhibitors. Furthermore, we aim to provide insights into the development prospects and emerging trends to offer guidance for the clinical application and inspiration for the development of novel PARP inhibitors and degraders.

Percutaneous Transforaminal Endoscopic Discectomy for Adjacent Segment Disease versus Lumbar Disc Herniation in Elderly Patients.

Purpose: Percutaneous transforaminal endoscopic discectomy (PTED) was used as a minimally invasive treatment option for lumbar disc herniation (LDH). However, studies focusing on the clinical outcomes of PTED for elderly patients with adjacent segment disease (ASD) were limited. This study aims to compare the clinical outcomes of PTED between ASD and LDH in elderly patients. Patients and Methods: This retrospective study enrolled 39 patients with ASD and 39 patients with LDH. Both groups had undergone PTED in Beijing Chaoyang Hospital from July 4, 2016 to July 30, 2021. Visual analog scale for back pain (VAS-BP) and leg pain (VAS-LP) and Oswestry disability index (ODI) were used to value the clinical outcomes of patients preoperatively, immediately postoperatively, 12, and 24 months postoperatively, and at final follow-up. Patients' satisfaction was evaluated based on the MacNab criteria. Results: All operations were completed. The excellent or good clinical outcomes at final follow-up was demonstrated by 87.15% (34/39) and 89.74% (35/39) in ASD and non-ASD patients, respectively. Clinical improvement was observed immediately postoperatively in both groups and sustained stability during the postoperative follow-up. The ASD group demonstrated significantly longer hospital stays (p = 0.02) and operative time (p < 0.01) than the non-ASD group. Conclusion: PTED is an effective and minimally invasive treatment option for revision surgery of ASD, especially for elderly patients. However, the long-term prognosis of PTED treating ASD still needs further exploration.

Recompression after percutaneous transforaminal endoscopic decompression for degenerative lumbar spinal stenosis: risk factors and outcomes of two different reoperation procedures.

Purpose: To determine the risk factors for recompression after percutaneous transforaminal endoscopic decompression (PTED) for the treatment of degenerative lumbar spinal stenosis (DLSS) and compare the outcomes of PTED and posterior lumbar interbody fusion (PLIF) as revision surgery. Methods: We retrospectively evaluated 820 consecutive DLSS patients who underwent PTED at our institution. 26 patients developed postoperative recompression and underwent reoperation. In total, 208 patients with satisfactory clinical outcomes were enrolled in the control group. The demographic and imaging data of each patient were recorded. Univariate and multivariate analyses were performed to assess risk factors for recompression. Additionally, patients with recompression were divided into PTED and PLIF groups according to the reoperation procedure. The clinical outcomes of the two groups were compared using independent-sample t-tests. Results: The grade of surgical-level disc degeneration [odds ratio (OR): 2.551, p = 0.045] and the number of disc degeneration levels (OR: 11.985, p < 0.001) were independent risk factors for recompression after PTED. There was no significant difference in the visual analog score (VAS) and Oswestry disability index (ODI) two weeks postoperatively between the PTED and PLIF groups for surgical treatment. However, the mean VAS of back pain (14.1 vs. 20.5, p = 0.016) and ODI (16.0 vs. 21.8, p = 0.016) of patients in the PLIF group were smaller than those in the PTED group at the final follow-up. Conclusion: More severe degeneration and degenerated levels indicate a higher recompression rate after PTED. Although both PTED and PLIF could achieve immediate relief postoperatively in the treatment of recompression, the final follow-up results showed that the outcome of PLIF appeared better than that of PTED.

Artificial intelligence automatic measurement technology of lumbosacral radiographic parameters.

Background: Currently, manual measurement of lumbosacral radiological parameters is time-consuming and laborious, and inevitably produces considerable variability. This study aimed to develop and evaluate a deep learning-based model for automatically measuring lumbosacral radiographic parameters on lateral lumbar radiographs. Methods: We retrospectively collected 1,240 lateral lumbar radiographs to train the model. The included images were randomly divided into training, validation, and test sets in a ratio of approximately 8:1:1 for model training, fine-tuning, and performance evaluation, respectively. The parameters measured in this study were lumbar lordosis (LL), sacral horizontal angle (SHA), intervertebral space angle (ISA) at L4-L5 and L5-S1 segments, and the percentage of lumbar spondylolisthesis (PLS) at L4-L5 and L5-S1 segments. The model identified key points using image segmentation results and calculated measurements. The average results of key points annotated by the three spine surgeons were used as the reference standard. The model's performance was evaluated using the percentage of correct key points (PCK), intra-class correlation coefficient (ICC), Pearson correlation coefficient (r), mean absolute error (MAE), root mean square error (RMSE), and box plots. Results: The model's mean differences from the reference standard for LL, SHA, ISA (L4-L5), ISA (L5-S1), PLS (L4-L5), and PLS (L5-S1) were 1.69°, 1.36°, 1.55°, 1.90°, 1.60%, and 2.43%, respectively. When compared with the reference standard, the measurements of the model had better correlation and consistency (LL, SHA, and ISA: ICC = 0.91-0.97, r = 0.91-0.96, MAE = 1.89-2.47, RMSE = 2.32-3.12; PLS: ICC = 0.90-0.92, r = 0.90-0.91, MAE = 1.95-2.93, RMSE = 2.52-3.70), and the differences between them were not statistically significant (p > 0.05). Conclusion: The model developed in this study could correctly identify key vertebral points on lateral lumbar radiographs and automatically calculate lumbosacral radiographic parameters. The measurement results of the model had good consistency and reliability compared to manual measurements. With additional training and optimization, this technology holds promise for future measurements in clinical practice and analysis of large datasets.

Targeting DNA methyltransferases for cancer therapy.

DNA methyltransferases (DNMTs) play a crucial role in genomic DNA methylation. In mammals, DNMTs regulate the dynamic patterns of DNA methylation in embryonic and adult cells. Abnormal functions of DNMTs are often indicative of cancers, including overall hypomethylation and partial hypermethylation of tumor suppressor genes (TSG), which accelerate the malignancy of tumors, worsen the condition of patients, and significantly exacerbate the difficulty of cancer treatment. Currently, nucleoside DNMT inhibitors such as Azacytidine and Decitabine have been approved by the FDA and EMA for the treatment of acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), and myelodysplastic syndrome (MDS). Therefore, targeting DNMTs is a very promising anti-tumor strategy. This review mainly summarizes the therapeutic effects of DNMT inhibitors on cancers. It aims to provide more possibilities for the treatment of cancers by discovering more DNMT inhibitors with high activity, high selectivity, and good drug-like properties in the future.