Xinxin Yang

Objective: To develop and validate a non-invasive urine-based TWIST1 methylation-specific qPCR assay for bladder cancer (BC) diagnosis and surveillance, addressing the clinical need for a reliable alternative to invasive cystoscopy.Methods: This multicenter study included a three-phase design. The discovery phase identified hypermethylated CpG sites within the TWIST1 promoter in matched BC/normal tissue samples (n=6). A targeted qMSP assay was developed and subsequently validated in a training cohort (n=728) and an independent multicenter validation cohort (n=1,233).Results: The assay demonstrated 87.8% sensitivity and 90.7% specificity in the training cohort. Validation confirmed 88.2% sensitivity and 86.8% specificity for primary BC. Sensitivity remained high across tumor stages: 81.3% (Ta), 94.2% (T1), and 100.0% (T2–4). Muscle-invasive and high-grade tumors showed higher sensitivity (97.1% and 95.6%, respectively). Specificity was 91.7% in healthy controls but lower in upper tract urothelial carcinomas. The assay exhibited high agreement with pyrosequencing (99.2% concordance), with a detection limit of 5% and low variability (CV<10%).Conclusion: The urinary TWIST1 methylation qPCR assay is a clinically robust, non-invasive tool for BC diagnosis and recurrence monitoring. It shows high accuracy across disease stages and may help reduce the need for repeated cystoscopy. However, its performance in distinguishing BC from upper tract tumors warrants further study.

Purpose To develop an explainable radio-pathomic graph deep-learning (RPGDL) system for multiscale spatial-contextual modeling of intratumoral heterogeneity (ITH) and evaluate its performance for the prediction of pathologic complete response (pCR) to neoadjuvant therapy (NAT) in breast cancer (BC). Materials and Methods The RPGDL system was developed from dual-center retrospective analysis of patients with biopsy-proven invasive BC (May 2018–August 2024). For each tumor, individual radiomic and pathomic graphs were generated from pretherapeutic MRI and hematoxylin and eosin-stained biopsy slide images, respectively. These graphs were then processed by three distinct graph neural networks (GNNs): radiomic, pathomic, and radio-pathomic GNNs. GNN performance was assessed with the area under the receiver operating characteristic curve (AUC), net reclassification index (NRI), and integrated discrimination improvement (IDI). A multifaceted approach was used to explain the GNNs’ predictions. Results The training/external test set included 582/468 patients from Centers I/II (mean ages, 52 ± 9/50 ± 10 years). The radiomic GNN achieved AUCs of 0.89 (95% CI 0.85–0.93, training) and 0.84 (95% CI 0.80–0.89, external test); the pathomic GNN achieved AUCs of 0.87 (95% CI 0.83–0.91, training) and 0.83 (95% CI 0.78– 0.88, external test), with no significant difference between them ( P >.05). The radio-pathomic GNN outperformed both single-modality GNNs (AUC [95% CI], 0.95 [0.92–0.98]/0.91 [0.87–0.94]; training/external test; P <.05; NRI and IDI confirmed). Pathomic graphs dominated probability increases for pCR predictions; while radiomic graphs drove probability decreases for non-pCR predictions. Multifaceted analyses verified GNNs’ explainability. Conclusion The developed RPGDL system enabled multiscale spatial-contextual ITH modeling for highperformance, explainable prediction of pCR to NAT in BC. ©RSNA, 2026

Background: Depression is a prevalent psychiatric disorder with high long‐term morbidities, recurrences, and mortalities. Despite extensive research efforts spanning decades, the cellular and molecular mechanisms of depression remain largely unknown. What's more, about one third of patients do not have effective anti‐depressant therapies, so there is an urgent need to uncover more mechanisms to guide the development of novel therapeutic strategies. Adenosine triphosphate (ATP) plays an important role in maintaining ion gradients essential for neuronal activities, as well as in the transport and release of neurotransmitters. Additionally, ATP could also participate in signaling pathways following the activation of postsynaptic receptors. By searching the website PubMed for articles about “ATP and depression” especially focusing on the role of extracellular ATP (eATP) in depression in the last 5 years, we found that numerous studies have implied that the insufficient ATP release from astrocytes could lead to depression and exogenous supply of eATP or endogenously stimulating the release of ATP from astrocytes could alleviate depression, highlighting the potential therapeutic role of eATP in alleviating depression. Aim: Currently, there are few reviews discussing the relationship between eATP and depression. Therefore, the aim of our review is to conclude the role of eATP in depression, especially focusing on the evidence and mechanisms of eATP in alleviating depression. Conclusion: We will provide insights into the prospects of leveraging eATP as a novel avenue for the treatment of depression.

Background: Acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) are closely related to the regulation of learning and memory. Nevertheless, whether sevoflurane has influence on cognition through regulating the expression of AChE and ChAT remains unclear.Methods: Aging rat model was established by subcutaneously injection of D‐galactose for 6 consecutive weeks. To determine the role of AChE and ChAT in sevoflurane‐induced cognitive impairment, the Morris water maze (MWM) was used to assess the cognitive and memory function after sevoflurane exposure. Then, the variations of AChE and ChAT was detected by western blotting analysis and quantitative real‐time polymerase chain reaction (qRT‐PCR) respectively.Results: Our result indicated that aging model rats had showed cognition decline at 2 hours and 1week after exposure to sevoflurane. Moreover, the expression of AChE and ChAT enhanced in rats that had inhaled sevoflurane. Interestingly, our study also found that the increase of oxygen concentration had a positive impact on the gene expression of ChAT.Conclusion: We have identified that the overexpression of AChE and ChAT improved significantly cognitive function after sevoflurane exposure.

INPLASY2020110070 Efficacy and safety of pasireotide for Cushing’s disease: A protocol for systematic review and meta-analysis Keywords: pasireotide; Cushing’s disease; protocol; systematic review; meta-analysis. Download PDF – 2020110070

Purpose: Infection with human papillomavirus (HPV) has been indicated to be a important risk factor for oropharyngeal squamous cell carcinoma (OPSCC). Primary ciliogenesis defects contribute to tumorigenesis, and OFD1 at centriolar satellites is a crucial suppressor of primary ciliogenesis. To identify novel markers associated with HPV-induced carcinogenesis, the interactions between HPV infection and primary ciliogenesis in the tumorigenesis and progression of OPSCC were investigated in this study. Patients and Methods: The 1530 OPSCC patients recruited in this research were treated from 2000 to 2017. Immunohistochemistry and RT-PCR were performed on tissue samples to compare the expression of p16, TSLP, TGFβ 1, IFNγ, OFD1, and their relationship with clinical characteristics of patients. Results: We speculate that the positive expression of p16 is related to early primary OPSCC, and the survival rate of p16 positive patients after radiotherapy and surgery is higher. Expression of TSLP on dendritic cells in HPV-positive OPSCC correlated with the expression of OFD1. HPV-positive OPSCC showed increased expression of OFD1 combined with reduced ciliogenesis. Hence, TSLP induced by HPV infection may reduce the invasive potential of OPSCC cells by promoting OFD1 expression, thereby inhibiting primary ciliogenesis. Conclusion: Our study demonstrated that HPV may be related to the progression of OPSCC by regulating OFD1 expression and primary ciliogenesis, making this protein a potential therapeutic target.

The ultimate goal of phototherapy based on nanoparticles, such as photothermal therapy (PTT) which generates heat and photodynamic therapy (PDT) which not only generates reactive oxygen species (ROS) but also induces a variety of anti-tumor immunity, is to kill tumors. In addition, due to strong efficacy in clinical treatment with minimal invasion and negligible side effects, it has received extensive attention and research in recent years. In this paper, the generations of nanomaterials in PTT and PDT are described separately. In clinical application, according to the different combination pathway of nanoparticles, it can be used to treat different diseases such as tumors, melanoma, rheumatoid and so on. In this paper, the mechanism of pathological treatment is described in detail in terms of inducing apoptosis of cancer cells by ROS produced by PDT, immunogenic cell death to provoke the maturation of dendritic cells, which in turn activate production of CD4+ T cells, CD8+T cells and memory T cells, as well as inhibiting heat shock protein (HSPs), STAT3 signal pathway and so on.

Background: Human papillomavirus (HPV) is a high-risk etiological factor for cervical and ovarian carcinomas. p16 protein can be used as a surrogate biomarker for HPV infection in high-risk tumors. A strong correlation between HPV infection and programmed death ligand 1 (PD-L1) protein expression has consistently been reported. Objective: Given this background, this study investigates the prevalence, prognostic and clinicopathologic features of HPV-related epithelial ovarian cancer (EOC) for the last 10 years in Northeast China to elucidate the involvement of p16 in the PD-L1 protein expression, tumorigenesis, and progression of EOC. Methods: Specimens from 310 patients diagnosed with EOC collected from 2006 to 2016 were analyzed by polymerase chain reaction (PCR) for HPV DNA, and overexpression of p16 by immunohistochemistry was also evaluated. Statistical analysis was performed to estimate the significant difference between HPV positive and negative patients, the correlation among HPV state, p16 and PD-L1 expression, and clinical presentation. Results: Overexpression of p16 protein and HPV DNA were present in 100 (32.3%) of the 310 cases, and correlated with high PD-L1 expression. There was a good concordance between HPV positivity, p16 protein overexpression and PD-L1 expression. The etiological fraction of HPV in EOC is substantially higher in Northeast China than other cohorts previously reported. Conclusion: Our study demonstrates that HPV infection and p16 overexpression is significantly associated with PD-LI expression in EOC, through the cooperative roles of dendritic cells (DCs) and IFN-γ, which may represent a promising strategy for therapeutic intervention in EOC.