Targeting tumour surface collage with hydrogel probe: a new strategy to enhance intraoperative imaging sensitivity and stability of bladder cancer.

PURPOSE: The incomplete resection of non-muscle invasive bladder cancer (NMIBC) augments the risk of disease recurrence. Imaging-guided surgery by molecular probes represents a pivotal strategy for mitigating postoperative recurrence. Traditional optical molecular probes, primarily composed of antibodies/peptides targeting tumour cells and fluorescent groups, are challenged by the high heterogeneity of NMIBC cells, leading to inadequate probe sensitivity. We have developed a collagen-adhesive probe (CA-P) to target the collagen within the tumour microenvironment, aiming to address the issue of insufficient imaging sensitivity. METHODS: The distribution characteristics of collagen in animal bladder cancer models and human bladder cancer tissues were explored. The synthesis and properties of CA-P were validated. In animal models, the imaging performance of CA-P was tested and compared with our previously reported near-infrared probe PLSWT7-DMI. The clinical translational potential of CA-P was assessed using human ex vivo bladder tissues. RESULTS: The distribution of collagen on the surface of tumour cells is distinct from its expression in normal urothelium. In vitro studies have demonstrated the ability of the CA-P to undergo a "sol-gel" transition upon interaction with collagen. In animal models and human ex vivo bladder specimens, CA-P exhibits superior imaging performance compared to PLSWT7-DMI. The sensitivity of this probe is 94.1%, with a specificity of 81%. CONCLUSION: CA-P demonstrates the capability to overcome tumour cell heterogeneity and enhance imaging sensitivity, exhibiting favorable imaging outcomes in preclinical models. These findings provide a theoretical basis for the application of CA-P in intraoperative navigation for NMIBC.

Viral infection and glioma: a meta-analysis of prognosis.

BACKGROUND: Glioma is the most common primary brain tumor, occurring due to the carcinogenesis of glial cells in the brain and spinal cord. Many aspects of the mechanism of its tumorigenesis remain unknown. The relationship between viral infection and glioma is one of the most important research aspects in this field. Currently, there is a lack of systematic reviews and meta-analyses to evaluate the effect of viral infection on the prognosis of glioma patients. The purpose of this study was to evaluate the relationship between viral infection and the prognosis of glioma patients, aimed at evaluating the prognostic value of the detection of viral infection. METHODS: Through careful and comprehensive retrieval of results from the PubMed, Embase, and Cochrane databases, eligible articles were selected strictly according to the inclusion and exclusion criteria. The regional sources, detection methods, detection indicators, patient survival, and other data from the samples in the papers were extracted, and the integrated analysis was conducted using Stata 15.1. We conducted a subgroup analysis of the relationship between the degree of infection and prognosis in cytomegalovirus (CMV) patients. RESULTS: A total of 11 studies were included in the analysis. Among them, 7 studies involved the relationship between CMV infection and the prognosis of patients with glioma, 2 studies involved human papillomavirus (HPV), 2 studies involved human herpesvirus-6 (HHV-6), and one study involved simian virus 40 (SV40), woolly monkey sarcoma virus (WMSV) and human endogenous retrovirus K113 (HERV-K113). In the CMV study, the pooled Hazard ratio (HR) of Overall survival (OS) was 1.024 (CI: 0.698-1.501), with a P value of 0.905. The pooled HR of Progression free survival (PFS) was 1.067 (CI: 0.770-1.478), with a P value of 0.697. The pooled HR value of low-degree infection versus high-degree infection was 1.476 (CI: 0.799-2.727), with a P value of 0.213. In the HPV study, the pooled HR of OS was 1.467 (CI: 0.552-3.901), with a P value of 0.443. CONCLUSION: CMV infection has no significant effect on the prognosis of glioma patients. Using the IEA as the detection index, the degree of CMV infection was found to have a significant impact on the prognosis of glioma patients; it was not found to possess a significant prognostic value after the integration of different indicators. Neither HPV nor HHV-6 infection has a significant effect on the prognosis of glioma patients. SV40 and WMSV infection are associated with poor prognosis in patients with low-grade glioma. TRIAL REGISTRATION: This meta-analysis registered in https://www.crd.york.ac.uk/PROSPERO/, PROSPERO ID: CRD42019127648.

Integrated multiomic analysis reveals disulfidptosis subtypes in glioblastoma: implications for immunotherapy, targeted therapy, and chemotherapy.

Introduction: Glioblastoma (GBM) presents significant challenges due to its malignancy and limited treatment options. Precision treatment requires subtyping patients based on prognosis. Disulfidptosis, a novel cell death mechanism, is linked to aberrant glucose metabolism and disulfide stress, particularly in tumors expressing high levels of SLC7A11. The exploration of disulfidptosis may provide a new perspective for precise diagnosis and treatment of glioblastoma. Methods: Transcriptome sequencing was conducted on samples from GBM patients treated at Tiantan Hospital (January 2022 - December 2023). Data from CGGA and TCGA databases were collected. Consensus clustering based on disulfidptosis features categorized GBM patients into two subtypes (DRGclusters). Tumor immune microenvironment, response to immunotherapy, and drug sensitivity were analyzed. An 8-gene disulfidptosis-based subtype predictor was developed using LASSO machine learning algorithm and validated on CGGA dataset. Results: Patients in DRGcluster A exhibited improved overall survival (OS) compared to DRGcluster B. DRGcluster subtypes showed differences in tumor immune microenvironment and response to immunotherapy. The predictor effectively stratified patients into high and low-risk groups. Significant differences in IC50 values for chemotherapy and targeted therapy were observed between risk groups. Discussion: Disulfidptosis-based classification offers promise as a prognostic predictor for GBM. It provides insights into tumor immune microenvironment and response to therapy. The predictor aids in patient stratification and personalized treatment selection, potentially improving outcomes for GBM patients.

UTRN as a potential biomarker in breast cancer: a comprehensive bioinformatics and in vitro study.

Utrophin (UTRN), known as a tumor suppressor, potentially regulates tumor development and the immune microenvironment. However, its impact on breast cancer's development and treatment remains unstudied. We conducted a thorough examination of UTRN using both bioinformatic and in vitro experiments in this study. We discovered UTRN expression decreased in breast cancer compared to standard samples. High UTRN expression correlated with better prognosis. Drug sensitivity tests and RT-qPCR assays revealed UTRN's pivotal role in tamoxifen resistance. Furthermore, the Kruskal-Wallis rank test indicated UTRN's potential as a valuable diagnostic biomarker for breast cancer and its utility in detecting T stage of breast cancer. Additionally, our results demonstrated UTRN's close association with immune cells, inhibitors, stimulators, receptors, and chemokines in breast cancer (BRCA). This research provides a novel perspective on UTRN's role in breast cancer's prognostic and therapeutic value. Low UTRN expression may contribute to tamoxifen resistance and a poor prognosis. Specifically, UTRN can improve clinical decision-making and raise the diagnosis accuracy of breast cancer.

Honokiol in glioblastoma recurrence: a case report.

Glioblastoma is the most common and aggressive primary tumor in the central nervous system. There is no standard of care for patients with recurrent GBM. Honokiol is a pleiotropic lignan and has the potential to be a potent and safe anticancer agent in human GBM when it is encapsulated by liposomes. We report an efficient and safe response to three phases of treatment with liposomal honokiol in a patient with recurrent glioblastoma.

Is extremely low frequency pulsed electromagnetic fields applicable to gliomas? A literature review of the underlying mechanisms and application of extremely low frequency pulsed electromagnetic fields.

Gliomas refer to a group of complicated human brain tumors with a low 5-year survival rate and limited therapeutic options. Extremely low-frequency pulsed electromagnetic field (ELF-PEMF) is a specific magnetic field featuring almost no side effects. However, the application of ELF-PEMF in the treatment of gliomas is rare. This review summarizes five significant underlying mechanisms including calcium ions, autophagy, apoptosis, angiogenesis, and reactive oxygen species, and applications of ELF-PEMF in glioma treatment from a clinical practice perspective. In addition, the prospects of ELF-PEMF in combination with conventional therapy for the treatment of gliomas are reviewed. This review benefits any specialists, especially oncologists, interested in this new therapy because it can help treat patients with gliomas properly.

Molecular profile reveals immune-associated markers of medulloblastoma for different subtypes.

Medulloblastoma, a common pediatric malignant tumor, has been recognized to have four molecular subgroups [wingless (WNT), sonic hedgehog (SHH), group 3, group 4], which are defined by the characteristic gene transcriptomic and DNA methylomic profiles, and has distinct clinical features within each subgroup. The tumor immune microenvironment is integral in tumor initiation and progression and might be associated with therapeutic responses. However, to date, the immune infiltrative landscape of medulloblastoma has not yet been elucidated. Thus, we proposed MethylCIBERSORT to estimate the degree of immune cell infiltration and weighted correlation network analysis (WGCNA) to find modules of highly correlated genes. Synthesizing the hub genes in the protein-protein interaction (PPI) network and modules of the co-expression network, we identify three candidate biomarkers [GRB2-associated-binding protein 1 (GAB1), Abelson 1 (ABL1), and CXC motif chemokine receptor type 4 (CXCR4)] via the molecular profiles of medulloblastoma. Given this, we investigated the correlation between these three immune hub genes and immune checkpoint blockade response and the potential of drug prediction further. In addition, this study demonstrated a higher presence of endothelial cells and infiltrating immune cells in Group 3 tumor bulk. The above results will be conducive to better comprehending the immune-related pathogenesis and treatment of medulloblastoma.

A Novel Classification of Glioma Subgroup, Which Is Highly Correlated With the Clinical Characteristics and Tumor Tissue Characteristics, Based on the Expression Levels of Gß and Gγ Genes.

PURPOSE: Glioma is a classical type of primary brain tumors that is most common seen in adults, and its high heterogeneity used to be a reference standard for subgroup classification. Glioma has been diagnosed based on histopathology, grade, and molecular markers including IDH mutation, chromosome 1p/19q loss, and H3K27M mutation. This subgroup classification cannot fully meet the current needs of clinicians and researchers. We, therefore, present a new subgroup classification for glioma based on the expression levels of Gß and Gγ genes to complement studies on glioma and Gßγ subunits, and to support clinicians to assess a patient's tumor status. METHODS: Glioma samples retrieved from the CGGA database and the TCGA database. We clustered the gliomas into different groups by using expression values of Gß and Gγ genes extracted from RNA sequencing data. The Kaplan-Meier method with a two-sided log-rank test was adopted to compare the OS of the patients between GNB2 group and non-GNB2 group. Univariate Cox regression analysis was referred to in order to investigate the prognostic role of each Gß and Gγ genes. KEGG and ssGSEA analysis were applied to identify highly activated pathways. The "estimate" package, "GSVA" package, and the online analytical tools CIBERSORTx were employed to evaluate immune cell infiltration in glioma samples. RESULTS: Three subgroups were identified. Each subgroup had its own specific pathway activation pattern and other biological characteristics. High M2 cell infiltration was observed in the GNB2 subgroup. Different subgroups displayed different sensitivities to chemotherapeutics. GNB2 subgroup predicted poor survival in patients with gliomas, especially in patients with LGG with mutation IDH and non-codeleted 1p19q. CONCLUSION: The subgroup classification we proposed has great application value. It can be used to select chemotherapeutic drugs and the prognosis of patients with target gliomas. The unique relationships between subgroups and tumor-related pathways are worthy of further investigation to identify therapeutic Gßγ heterodimer targets.

MicroRNAs as Diagnostic Biomarkers in Primary Central Nervous System Lymphoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Diagnosing primary central nervous system lymphoma (PCNSL) remains a challenge. MicroRNAs (miRNAs) are promising noninvasive markers for the identification of PCNSL. The present study aims to assess the diagnostic value of miRNAs for PCNSL patients as biomarkers. METHODS: We systematically searched PubMed, Embase, and the Cochrane library from inception to January 31, 2021. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), together with the summary receiver operator characteristic (SROC) curve, and the area under the SROC curve (AUC) value were used to estimate the overall diagnostic performance. We used Q statistic and I2 to test heterogeneity and used subgroup analyses to investigate the source of heterogeneity. The statistical analyses were independently performed by two investigators using Stata 14.0 and Revman 5.3. RESULTS: In total, 11 studies from 6 records were included in the current meta-analysis with 281 PCNSL patients and 367 controls. Our statistical analysis demonstrated that the pooled sensitivity, specificity, PLR, NLR, DOR, and AUC were 0.91 (95% CI 0.84-0.95), 0.88 (95% CI 0.84-0.91), 7.48 (95% CI 5.71-9.78), 0.11 (95% CI 0.06-0.19), 70 (95% CI 35-142), and 0.90 (95% CI 0.87-0.92), respectively. The studies had substantial heterogeneity (I2 = 54%, 95% CI 0-100). Two subgroup analyses were conducted based on the type of specimen and miRNAs profiled. CONCLUSIONS: This meta-analysis indicated that miRNAs were suitable as noninvasive diagnostic biomarkers for PCNSL with high accuracy. In addition, both cerebrospinal fluid-based and blood-based miRNAs assays for PCNSL detection were considered reliable for clinical application. MicroRNA-21 assays also seemed to be more accurate in the diagnosis of PCNSL. Good quality studies with large samples should be conducted to verify our results.

Social Policy Responses to the Covid-19 Crisis in China in 2020.

The 2020 coronavirus pandemic has catapulted China into a serious social and political crisis. This article focuses upon how Chinese social policy has responded to the Covid-19 crisis. It reveals that the Chinese welfare state has woven a comprehensive social safety net to mitigate the social suffering of Chinese society in the mid- and post-crisis periods. Different types of social policy programs have been combined and synthesized, including social insurance, social assistance, and social welfare arrangements. Facing the challenges of the new risks caused by the pandemic, the collaboration of the Chinese state and intermediary social welfare organizations has played a crucial role in providing both cash benefits and social services (benefits in kind). For the first time, social policy in China has acted as a major player for coping with the negative outcomes of a pandemic. This article concludes that the pandemic-related crisis has justified an interventionist approach and logic, driven by the state's welfare system, which favors a model of "big government". However, this model also requires justification and legitimation.

Trauma and pulmonary thromboembolism: an experimental study on their correlation.

OBJECTIVE: To investigate the correlation between trauma and pulmonary thromboembolism. METHODS: Comminuted fractures and extensive soft-tissue contusion at both hind limbs were made by a falling weight from a height in 16 rabbits. Lung perfusion scanning was performed to obtain the radioactivity counts before trauma, at 1 h, 48 h and 96 h after trauma. All the data were divided into 4 groups based on the above 4 time points. The rabbits were sacrificed when positive findings on the pulmonary perfusion scanning appeared. Their lungs were harvested to be paraffin-embedded and stained with hematoxylin-erosin method for histological examination of thromboembolism. The randomized block design ANOVA and the method of least significant difference (LSD) were used for statistical analysis of the radioactivity counts. RESULTS: The histological findings showed that pulmonary embolism developed in 6 of the 16 rabbits (37.5%). Five of the 6 pulmonary embolism rabbits presented neither clinical symptoms nor positive pulmonary embolism manifestations in the lung perfusion scanning. A significant difference was found in lung perfusion radioactivity between the pre-traumatic, post-traumatic 1h groups and post-traumatic 48 h and 96 h groups(P less than 0.05). CONCLUSIONS: Fractures of the hind limbs accompanied with extensive soft-tissue contusion may cause pulmonary micro-embolism that is not sensitive to lung perfusion scanning and tends to have no clinical symptoms. Pulmonary embolism development may take more than two days after trauma.

Blocking transforming growth factor-beta receptor signaling down-regulates transforming growth factor-beta1 autoproduction in keloid fibroblasts.

OBJECTIVE: To study transforming growth factor-beta1 (TGF-beta1) autoproduction in keloid fibroblasts and the regulation effect of blocking TGF-beta intracellular signaling on rhTGF-beta1 autoproduction. METHODS: Keloid fibroblasts cultured in vitro were treated with either rhTGF-beta1 (5 ng/ml) or recombinant adenovirus containing a truncated type II TGF-beta receptor gene (50 pfu/cell). Their effects of regulating gene expression of TGF-beta1 and its receptor I and II were observed with Northern blot. RESULTS: rhTGF-beta1 up-regulated the gene expression of TGF-beta1 and receptor I, but not receptor II. Over-expression of the truncated receptor II down-regulated the gene expression of TGF-beta1 and its receptor I, but not receptor II. CONCLUSIONS: TGF-beta1 autoproduction was observed in keloid fibroblasts. Over-expression of the truncated TGFbeta receptor II decreased TGF-beta1 autoproduction via blocking TGF-beta receptor signaling.

[The experimental study of creating a new rat scarring model by inserting absorbable gelatin sponge into rats' excisional wounds].

OBJECTIVE: To explore the possibility of creating a rat new scar model by inserting gelatin sponge into rat excisional wounds. METHODS: Two full-thickness wounds were created in each of total 49 SD rats. In the Experimental group (n = 19), a regular incisional wound (1 cm) was created on the left side, and an excisional wound of 1.0 cm x 0.2 cm was created on the right side with a gelatin sponge inserted. In control 1 group (n = 15), an excisional wound with sponge insertion was created on both sides of rats. In control 2 group (n = 15), two excisional wounds were created on both sides, and only one side wounds were inserted with a sponge. Animals were sacrificed at various time points for different examinations. RESULTS: The wound/scar width increased 4 - 11 times in inserted wounds than in regular incisional wounds (P < 0.01), with an obvious delay of epithelialization. No difference in wound/scar width was found in both sides of wounds of control 1 group at various locations. In contrast to the linear scar of sponge-inserted wounds, contracted and irregular scar was found in non-inserted wounds of control 2 group. CONCLUSIONS: Gelatin sponge insertion can create a thick linear scar in rat wounds, and thus provides a new model for scar research.

[Overexpression of truncated type II transforming growth factor-beta receptor in dermal fibroblasts].

OBJECTIVE: To study the effect of overexpression of truncated type II TGF-beta receptor on transforming growth factor-beta 1(TGF-beta 1) autoproduction in normal dermal fibroblasts. METHODS: In vitro cultured dermal fibroblasts were treated with recombinant human TGF-beta 1(rhTGF-beta 1) (5 ng/ml) or recombinant adenovirus containing truncated type II TGF-beta receptor gene (50 pfu/cell). Their effects on regulating gene expression of TGF-beta 1 were observed with Northern blotting. RESULTS: rhTGF-beta 1 up-regulated the gene expression of TGF-beta 1 and type I procollagen. Overexpression of truncated receptor II down-regulated the gene expression of TGF-beta 1. CONCLUSION: Overexpression of the truncated TGF-beta receptor II decreases TGF-beta 1 autoproduction via blocking TGF-beta receptor signal. The results may provided a new strategy for scar gene therapy.