Tao Wu’s research while affiliated with Nanchang University and other places

3559 Background: Circulating tumor DNA (ctDNA) has shown potential in predicting the efficacy of neoadjuvant treatment for colorectal cancer (CRC). However, evidence is limited for patients with deficient mismatch repair (dMMR) / microsatellite instability-high (MSI-H) CRC, who respond well to immunotherapy. This study explores an optimal ctDNA-guided neoadjuvant immunotherapy (nIT) strategy in locally advanced CRC (LACRC) patients with dMMR/MSI-H. Methods: We conducted a single-center, open-label, phase 2 trial named WINDOW involving dMMR/MSI-H LACRC patients. Patients received the anti-PD-1 antibody tislelizumab every three weeks. ctDNA was monitored at baseline, after 2, 4, 5, or even 6 to 8 cycles, and during post-watch-and-wait (W&W) or post-surgery periods using the Signatera platform. Starting from the 4th cycle, patients with two consecutive ctDNA-negative results were eligible for the W&W approach. Those who did not achieve ctDNA-negative or turned positive during follow-up continued immunotherapy. Surgery was performed for patients not meeting W&W criteria by the 8th cycle. The primary endpoint was the complete response (CR) rate, including ctDNA-negative clinical complete response (cCR) and pathological complete response (pCR). The trial is registered at ClinicalTrials.gov (NCT06477991). Results: From January 2023 to May 2024, 24 patients with stage II-III dMMR/MSI-H CRC were enrolled, including 18 with colon cancer and 6 with rectal cancer. At baseline, all patients had detectable ctDNA. After nIT, 87.5% (21/24) achieved two consecutive ctDNA-negative results. Among the remaining three, two underwent surgery due to sustained ctDNA-positivity (both TRG3), while one showed continuous ctDNA decrease despite obstruction and achieved pCR. One patient required emergency surgery for perforation (confirmed as pCR), while 20 were managed with the W&W strategy. Of these, 90% (18/20) achieved ctDNA negativity after two cycles, and 95% (19/20) after five cycles of nIT. With a median follow-up of 20.3 months (range: 8.7–25.0 months), none experienced recurrence, resulting in an overall CR rate of 91.7% (22/24). Notably, if ctDNA remained positive after the 5th cycle, the CR rate was only 25% (1/4), while it reached 100% (20/20) if ctDNA became negative. From the perspective of organ preservation, only 45.5% (10/22) of patients avoided surgery based on imaging alone; however, with ctDNA-guided management, 83.3% (20/24) avoided surgery. Conclusions: NIT demonstrates high efficacy in dMMR/MSI-H LACRC. The ctDNA-guided W&W strategy significantly improves organ preservation rates. Monitoring ctDNA negativity after the 5th cycle of nIT is a crucial marker of high CR rates, suggesting this cycle may represent the optimal monitoring window during nIT. Clinical trial information: NCT06477991 .

Objective The purpose of this study was to investigate the role of ⁶⁸Ga-labeled prostate specific membrane antigen HBED-CC (⁶⁸Ga-PSMA-11) PET/MRI in primary staging and to evaluate the relationship between PSMA-derived parameters and clinicopathological characteristics in newly diagnosed prostate cancer (PCa). Materials and methods This study reports the findings from 72 patients newly diagnosed with primary PCa, all of whom underwent ⁶⁸Ga-PSMA-11 PET/MRI scans. Calculated the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ⁶⁸Ga-PSMA-11 PET/MRI for T, N, M staging, respectively. The maximum standardized uptake value (SUVmax), PSMA-tumor volume (PSMA-TVp), and total lesion-PSMA (TL-PSMAp) of primary lesion, PSMA-TV of total lesions (PSMA-TVt), and TL-PSMA of total lesions (TL-PSMAt) were measured, and Spearman correlation analysis was performed to assess their correlation with baseline prostate-specific antigen (PSA). Non-parametric Mann–Whitney U test was conducted to assess the difference of PSMA-derived parameters among clinicopathological characteristics of PCa. Receiver operating characteristic (ROC) curve was used to evaluate the performance of PSMA-derived parameters in diagnosing the clinicopathological characteristics of PCa. Results The overall accuracy of ⁶⁸Ga-PSMA-11 PET/MRI in detecting T staging of PCa was 80.7%. Diagnostic accuracy for T2a, T2b, T2c, T3a, and T3b were 94.2%, 92.3%, 90.4%, 90.4%, and 94.2%, respectively. Diagnostic accuracy for N and M staging were 96.1% and 97.2% based on patients-level, respectively. There were significant correlation between the SUVmax, PSMA-TVp, TL-PSMAp, PSMA-TVt, TL-PSMAt and baseline PSA values. Significant differences were observed in SUVmax, PSMA-TVp, TL-PSMAp, PSMA-TVt, and TL-PSMAt between T3 and T2 staging. Statistical differences were observed in SUVmax, TL-PSMAp, PSMA-TVt, and TL-PSMAt between Gleason Score (GS) > 7 and GS ≤ 7, as well as positive and negative regional lymph node metastasis. TL-PSMAt show the highest value in assessing clinicopathological characteristics. Conclusions ⁶⁸Ga-PSMA-11 PET/MRI can provide accurate TNM staging for PCa, particularly in local staging. TL-PSMAt accurately evaluate overall tumor burden and aids in diagnosing clinicopathological characteristics in mid-to-late-stage patients, outperforming SUVmax.

The activation of pyrin domain-containing-3 (NLRP3) inflammasome in macrophages is a risk factor accelerating the progression of atherosclerosis (AS). Here, the function of pellino 1 (Peli1) in regulating the activation of NLRP3 inflammasome during the development of AS was investigated. Our results showed that Y-box binding protein 1 (YB-1) knockdown could inhibit the progression of AS in vivo, and YB-1 silencing repressed oxidized low-density lipoprotein (ox-LDL)-mediated lipid accumulation and inflammation in macrophages by inactivating NLRP3 inflammasome. E3 ubiquitination ligase Peli1 mediated ubiquitination-dependent degradation of YB-1 during AS progression. Moreover, it was found that YTH domain-containing 2 (YTHDC2) recognized methyltransferase-like 3 (METTL3)-mediated Peli1 N6-methyladenosine (m⁶A) modification and mediated Peli1 mRNA degradation. Rescue studies revealed that YB-1 upregulation abrogated the repressive effect of Peli1 upregulation on AS progression both in vitro and in vivo. Taken together, Peli1, regulated by m⁶A modification, inhibited YB-1-mediated activation of NLRP3 inflammasome in macrophages by promoting YB-1 ubiquitination to suppress the progression of AS.

Purpose: To evaluate the long-term efficacy and safety of secukinumab in pediatric patients with generalized pustular psoriasis (GPP). Materials and methods: A retrospective study was conducted from July 2021 to July 2024, including 10 children with GPP. Patients were divided into two age groups: children aged 0–3 years received 75 mg of secukinumab, while those aged 3–12 years received 150 mg. Secukinumab was administered subcutaneously at weeks 0, 1, 2, 3, and 4, followed by maintenance every 4 weeks. Treatment response was evaluated using the Generalized Pustular Psoriasis Area and Severity Index (GPPASI), Japanese Dermatological Association (JDA) score, and Infants’/Children’s Dermatology Life Quality Index (IDLQI/CDLQI). Results: By week 1, all patients achieved GPPASI-50 and mild JDA scores. By week 2, eight patients reached GPPASI-100, and nine achieved JDA scores of 0/1. Between weeks 12 and 70, all patients maintained GPPASI-100 and JDA scores of 0. Minimal relapses occurred in four patients, and one experienced five flares. The mean IDLQI/CDLQI improved from 21.8 at baseline to 0.4 by week 4, with sustained improvements throughout. Conclusions: Secukinumab demonstrated long-term efficacy and safety in pediatric GPP, significantly improving clinical outcomes and quality of life, with no serious adverse events reported.

Our study examined the relationships and interactions among 30 genes related to the NOD-like receptor protein 3 (NLRP3) inflammasome. We identified 368 interconnections between these 30 genes, with NLRP3 participating in 38 interactions. The potential roles of these genes in atherosclerosis were evaluated based on protein–protein interaction networks and coexpression analysis. We identified differential expression in 20 genes, five of which were significantly upregulated: P2RX7, CASP1, CD36, GBP5, and PYCARD. We also observed a strong positive association between P2RX7 and PYCARD and as a notable negative association between RELA and CD36. Furthermore, our analysis revealed a clear association between the expression of inflammasome-associated genes and immune cell infiltration in disease specimens. To diagnose AS, a logistic regression model based on six inflammasome-related genes, achieved an Area under the curve of 0.996, indicating excellent diagnostic performance. Genomic enrichment analysis indicated that inflammasome-related genes were primarily involved in various pathways, such as hypertrophic cardiomyopathy and ribosomal function. To validate our findings, we confirmed the expression of risk genes in AS cells using qRT-PCR and Western blot techniques. Additionally, we observed a shift toward M2 polarization in THP-1 macrophages upon P2RX7 knockdown, further supporting our findings.

To assess knowledge, attitude, and practice (KAP) of stroke and thrombectomy among medical students in Henan, China. A cross-sectional study was conducted on medical students from 5 universities in Henan, China between June and September, 2022, using a self-administered questionnaire. A total of 1105 medical students [697 (62.1%) females] participated. Their mean KAP scores were 11.1 ± 2.90, 35.37 ± 4.94, and 21.48 ± 5.51 out of 14, 44, and 24, respectively. Structural equation modeling revealed that, age (estimate = 0.351, P = .005) and education (estimate = 0.370, P = .024) positively affected knowledge, while major (estimate = −0.128, P = .017), internship experience in neurosurgery or neurology (estimate = −1.321, P < .001), and family history of stroke (estimate = −0.557, P < .001) negatively influenced knowledge. Knowledge (estimate = 0.649, P < .001) and having seniors over the age of 60 at home (estimate = 1.228, P = .001) had positive effects on attitudes, while internship experience in neurosurgery or neurology (estimate = −0.471, P = .090) and family history of stroke (estimate = −0.596, P = .020) had negative impact on attitudes. Moreover, knowledge (estimate = 0.230, P < .001) and attitudes (estimate = 0.628, P < .001) positively influenced practices, whereas sex (estimate = −1.141, P < .001), internship experience in neurosurgery or neurology (estimate = −0.578, P = .025), and family history of stroke (estimate = −0.523, P = .027) negatively influenced practices. Medical students in Henan, China showed adequate knowledge, positive attitude, and proactive practice toward stroke and thrombectomy. Age, sex, education, major, internship experience in neurosurgery or neurology, family history of stroke, having seniors over the age of 60 at home might have impact on their KAP.

Mesenchymal stem cells (MSCs), as a stem cell type with multiple differentiation potentials and immune regulatory abilities, have shown broad prospects in the treatment of ischemic stroke in recent years. The main characteristics of MSCs include their self-renewal ability, differentiation potential for different types of cells, and the ability to secrete various bioactive factors such as cytokines, chemokines, and growth factors, which play a key role in tissue repair and regeneration. In the treatment of ischemic stroke, MSCs exert therapeutic effects through various mechanisms, including promoting vascular regeneration of damaged brain tissue, reducing inflammatory responses, and protecting neurons from damage caused by apoptosis. Research have shown that MSCs can promote the repair of ischemic areas by releasing neurotrophic factors and angiogenic factors, while inhibiting immune responses triggered by ischemia, thereby improving neurological function. With the in-depth study of its biological mechanism, MSCs have gradually shown good safety and effectiveness in clinical applications. Therefore, fully exploring and utilizing the potential of MSCs in the treatment of ischemic stroke may provide new ideas and solutions for future neural repair and regenerative medicine.

Study Design：A biomimetic intervertebral disc (IVD) scaffold was fabricated through the integration of magnetic resonance imaging (MRI) and 3D printing technology, and subsequently underwent in vitro experimentation. Objective：This study aimed to create a new IVD scaffold using MRI grayscale image analysis and GE-DLP technology to mimic the natural structure of the IVD for improved biomechanical performance and cell compatibility, potentially providing a new treatment option for IVD regeneration. Summary of Background Data: The IVD is a critical component of the spine, and its damage or degeneration can lead to severe back and neck pain. Current treatments provide symptomatic relief but do not address structural damage. Tissue engineering offers a promising alternative, with bio-scaffolds being a key element for IVD regeneration. Methods: In this study, we constructed a 3D model of the IVD from MRI scans of a healthy volunteer and processed the grayscale images to distinguish between tissue types. Exposure times were adjusted based on grayscale values, and GE-DLP technology was applied to fabricate the biomimetic IVD scaffold in a single integrated process using a bicomponent polymer network (BCN) hydrogel laden with nucleus pulposus stem cells (NPMSCs). The microstructure and porosity of the scaffold were analyzed using scanning electron microscopy (SEM), and the elastic modulus across the radial distribution was tested via nanoindentation. The biomechanical performance was evaluated using finite element analysis (FEA). For biocompatibility assessment, cytoskeleton staining was utilized to observe cell morphology, and cell viability was evaluated using Calcein/PI staining. Results: The biomimetic IVD scaffold exhibited gradient changes in elastic modulus and pore size, consistent with the ultrastructure and biomechanical characteristics of the natural IVD. FEA indicated that the scaffold's response in terms of displacement, strain, and stress closely resembled that of an actual IVD, particularly during simulations of left rotation and left lateral bending. SEM revealed a network structure of pores with varying sizes in different regions of the scaffold, which is crucial for cell adhesion and growth. The scaffold also demonstrated high biocompatibility, with cell survival rates maintained at a high level over a seven-day culture period. Conclusion: In this research, we have successfully engineered a novel biomimetic IVD scaffold with excellent static structural integrity and biomechanical performance by integrating MRI image analysis with GE-DLP technology. Level of Evidence: N/A

BACKGROUND Intracranial arterial narrowing is a significant factor leading to brief episodes of reduced blood flow to the brain, known as transient ischemic attacks, or full-blown strokes. While atherosclerosis is commonly associated with intracranial arterial narrowing, it is frequently of a non-atherosclerotic nature in younger patients. CASE SUMMARY Here, we present the case of a young stroke patient with narrowing of the middle cerebral artery (MCA), characterized as non-atherosclerotic lesions, who experienced an ischemic stroke despite receiving standard drug therapy. The patient underwent digital subtraction angiography (DSA) to assess the entire network of blood vessels in the brain, revealing significant narrowing (approximately 80%) in the M1 segment of the right MCA. Subsequently, the patient underwent Drug-Coated Balloon Angioplasty to treat the stenosis in the right MCA's M1 segment. Follow-up DSA confirmed the resolution of stenosis in this segment. Although the remaining branches showed satisfactory blood flow, the vessel wall exhibited irregularities. A review of DSA conducted six months later showed no evident stenosis in the right MCA, with a smooth vessel wall. CONCLUSION The use of drug-coated balloon angioplasty demonstrated favorable outcomes in repairing and reshaping the blood vessel wall in young patients. Therefore, it may be considered a promising treatment option for similar cases.

Background Colon adenocarcinoma (COAD) is one of the most common malignant tumors. The interplay involving ferroptosis between tumor and immune cells plays a crucial in cancer progression. However, the biological basis of this interplay in COAD development remains elusive. Methods Transcriptome data of COAD samples were obtained from The Cancer Genome Atlas and National Center for Biotechnology Information databases. Using single-sample gene set enrichment analysis, we calculated the ferroptosis score (FS) and immune cell infiltration levels for each sample, leveraging the expression levels of genes related to ferroptosis and various immune cell types. Samples with FSs greater than the 75th percentile were classified into the high-FS subgroup, while those below the 25th percentile were categorized as the low-FS subgroup. Moreover, tumor tissue samples and adjacent normal tissue samples were collected from twenty colon patients. Using real-time quantitative polymerase chain reaction, we validated the expression of certain genes in these samples. Results The COAD samples with high FSs experienced favorable survival probability and heightened sensitivity to anticancer drugs, with FSs negatively associated with the pathological stages. Moreover, the up-regulated genes in high-FS subgroup exhibited enrichment in immune-related pathways, suggesting a correlation between immunity and ferroptosis. Importantly, we discovered a key lncRNA-mRNA co-expression network linking tumor cell ferroptosis and immune infiltration (e.g., neutrophil) in the progression and classification of COAD. Further analysis identified several ferroptosis-related lncRNAs (e.g., RP11-399O19.9) within this network, indicating their potential roles in COAD progression and deserving in-depth study. Conclusions Our findings provide novel insights into the underlying biological basis, particularly involving lncRNAs, at gene expression level associated with ferroptosis in COAD and cancer therapy. Nevertheless, further analysis and validation are required to expand the findings.