Molecular basis of CX-5461-induced DNA damage response in primary vascular smooth muscle cells.

Our previous studies have shown that the novel selective RNA polymerase I inhibitor CX-5461 suppresses proliferation of vascular smooth muscle cells, mainly by inducing DNA damage response (DDR), including activations of ataxia telangiectasia mutated (ATM)/ATM and Rad3-related (ATR) and p53. Currently, there is no information about the molecular mechanism(s) underlying CX-5461-induced DDR in vascular cells, while the results obtained in cancer cells and immortalized cell lines are controversial. In this study, we examined the responses of various DDR pathways to CX-5461 treatment in primary aortic smooth muscle cells isolated from normal adult Sprague Dawley rats. We demonstrated that CX-5461-induced DDR was not associated with activations of the nucleotide excision repair, DNA mismatch repair, or the non-homologous end joining pathways, while the homologous recombination pathway was activated. However, the alkaline comet assay did not show massive DNA double strand breaks in CX-5461-treated cells. Instead, CX-5461-induced DDR appeared to be related to induction of DNA replication stress, which was not attributable to increased formation of G-quadruplex or R-loop structures, but might be explained by the increased replication-transcription conflict. CX-5461-induced DDR was not exclusively confined to rDNA within the nucleolar compartment; the extra-nucleolar DDR might represent a distinct secondary response related to the downregulated Rad51 expression in CX-5461-treated cells. In summary, we suggest that DNA replication stress may be the primary molecular event leading to downstream ATM/ATR and p53 activations in CX-5461-treated vascular smooth muscle cells. Our results provide further insights into the molecular basis of the beneficial effects of CX-5461 in proliferative vascular diseases.

Percutaneous Endoscope-assisted Visualized Implantation of Puncture Cylindrical Electrodes for Spinal Cord Stimulation: A Cadaveric Feasibility Study.

BACKGROUND: Spinal cord stimulation is an established technique wherein diverse electrode types are strategically implanted within the spinal epidural space for neuromodulation. Traditional percutaneous puncture cylindrical electrodes (PEs) are predominantly implanted by interventionalists utilizing a percutaneous technique under the monitor of radiation, which is a nonvisualized procedure. OBJECTIVE: Our study aimed to assess the feasibility of percutaneous endoscope-assisted visualized implantation approach for PEs, delineating its specific merits and demerits compared to the traditional method. STUDY DESIGN: Laboratory study with Institutional Review Board Number B2023-056SETTING: Clinical Anatomy Research Center, Fudan University. METHODS: Eight freshly procured adult cadavers (4 women and 4 men) were operated on in this study. They were divided into either Group A or Group B, each encompassing 4 cadavers. Group A was subjected to endoscope-assisted PEs implantation, whereas Group B followed the conventional PEs implantation route.In both groups the operative time of introducer needles placement (OTNP), total operative time (TOT), fluoroscopy time of introducer needles placement (FTNP), and total fluoroscopy time (TFT) were documented and analyzed. Furthermore, the precise positioning of the PEs and any ensuing complications were systematically examined. RESULTS: Both Group A and Group B successfully executed all predetermined surgical steps. A total of 16 PEs were implanted (dual electrodes in each cadaver): 8 using the percutaneous endoscope-assisted visualized approach (Group A) and 8 via the traditional methodology (Group B). Group A's mean ± SD durations for OTNP, TOT, FTNP, and TFT were 10.25 ± 1.03 minutes, 31.63 ± 5.87 minutes, 4.58 ± 1.35 seconds, and 43.73 ± 14.46 seconds, respectively. In contrast, Group B exhibited mean ± SD times of 11.55 ± 2.81 minutes, 44.75 ± 7.85 minutes, 23.53 ± 4.16 seconds, and 66.30 ± 6.35 seconds for the same metrics. No discernible statistical difference in OTNP and TOT emerged between the groups. However, Group A demonstrated reduced durations for both FTNP and TFT compared to Group B. The optimal position of the PEs was verified via fluoroscopy, with no recorded instances of dura rupture. These outcomes suggest that this endoscope-assisted technique neither increases surgical time nor compromises efficacy. Instead, it leads to a marked reduction in fluoroscopic duration relative to the traditional methodology. LIMITATIONS: Anatomical study on a human cadaver, the quantity of cadavers, and the procedure's steep learning curve. CONCLUSION: With the assistance of percutaneous spinal endoscopy, introducer needles can be punctured through the ligamentum flavum at the anticipated interlaminar window locus under direct visualization, improving the convenience of the puncture and reducing fluoroscopic exposure. It is a viable alternative for surgeons from diverse training backgrounds to implant PEs, particularly benefiting those well-versed in endoscopic spine surgery techniques.

Components, Formulations, Deliveries, and Combinations of Tumor Vaccines.

Tumor vaccines, an important part of immunotherapy, prevent cancer or kill existing tumor cells by activating or restoring the body's own immune system. Currently, various formulations of tumor vaccines have been developed, including cell vaccines, tumor cell membrane vaccines, tumor DNA vaccines, tumor mRNA vaccines, tumor polypeptide vaccines, virus-vectored tumor vaccines, and tumor-in-situ vaccines. There are also multiple delivery systems for tumor vaccines, such as liposomes, cell membrane vesicles, viruses, exosomes, and emulsions. In addition, to decrease the risk of tumor immune escape and immune tolerance that may exist with a single tumor vaccine, combination therapy of tumor vaccines with radiotherapy, chemotherapy, immune checkpoint inhibitors, cytokines, CAR-T therapy, or photoimmunotherapy is an effective strategy. Given the critical role of tumor vaccines in immunotherapy, here, we look back to the history of tumor vaccines, and we discuss the antigens, adjuvants, formulations, delivery systems, mechanisms, combination therapy, and future directions of tumor vaccines.

Cell Membrane Engineered Polypeptide Nanonets Mimicking Macrophage Aggregates for Enhanced Antibacterial Treatment.

Drug-resistant bacterial infections and their lipopolysaccharide-related inflammatory complications continue to pose significant challenges in traditional treatments. Inspired by the rapid initiation of resident macrophages to form aggregates for efficient antibacterial action, this study proposes a multifunctional and enhanced antibacterial strategy through the construction of novel biomimetic cell membrane polypeptide nanonets (R-DPB-TA-Ce). The design involves the fusion of end-terminal lipidated polypeptides containing side-chain cationic boronic acid groups (DNPLBA) with cell membrane intercalation engineering (R-DPB), followed by coordination with the tannic acid-cerium complex (TA-Ce) to assemble into a biomimetic nanonet through boronic acid-polyphenol-metal ion interactions. In addition to the ability of RAW 264.7 macrophages cell membrane components' (R) ability to neutralize lipopolysaccharide (LPS), R-DPB-TA-Ce demonstrated enhanced capture of bacteria and its LPS, leveraging nanoconfinement-enhanced multiple interactions based on the boronic acid-polyphenol nanonets skeleton combined with polysaccharide. Utilizing these advantages, indocyanine green (ICG) is further employed as a model drug for delivery, showcasing the exceptional treatment effect of R-DPB-TA-Ce as a new biomimetic assembled drug delivery system in antibacterial, anti-inflammatory, and wound healing promotion. Thus, this strategy of mimicking macrophage aggregates is anticipated to be further applicable to various types of cell membrane engineering for enhanced antibacterial treatment.

Polycyclic Aromatic Hydrocarbons' Impact on Crops and Occurrence, Sources, and Detection Methods in Food: A Review.

Polycyclic aromatic hydrocarbons (PAHs) represent a category of persistent organic pollutants that pose a global concern in the realm of food safety due to their recognized carcinogenic properties in humans. Food can be contaminated with PAHs that are present in water, air, or soil, or during food processing and cooking. The wide and varied sources of PAHs contribute to their persistent contamination of food, leading to their accumulation within these products. As a result, monitoring of the levels of PAHs in food is necessary to guarantee the safety of food products as well as the public health. This review paper attempts to give its readers an overview of the impact of PAHs on crops, their occurrence and sources, and the methodologies employed for the sample preparation and detection of PAHs in food. In addition, possible directions for future research are proposed. The objective is to provide references for the monitoring, prevention, and in-depth exploration of PAHs in food.

Neutrophil Extracellular Traps-Inspired Bismuth-Based Polypeptide Nanonets for Synergetic Treatment of Bacterial Infections.

Excessive use of antibiotics and the formation of bacterial biofilms can lead to persistent infections caused by drug-resistant bacteria, rendering ineffective immune responses and even life-threatening. There is an urgent need to explore synergistic antibacterial therapies across all stages of infection. Drawing inspiration from the antibacterial properties of neutrophil extracellular traps (NETs) and integrating the bacterial biofilm dispersal mechanism involving boronic acid-catechol interaction, the multifunctional bismuth-based polypeptide nanonets (PLBA-Bi-Fe-TA) are developed. These nanonets are designed to capture bacteria through a coordination complex involving cationic polypeptides (PLBA) with boronic acid-functionalized side chains, alongside metal ions (bismuth (Bi) and iron (Fe)), and tannic acid (TA). Leveraging the nanoconfinement-enhanced high-contact network-driven multiple efficiency, PLBA-Bi-Fe-TA demonstrates the excellent ability to swiftly capture bacteria and their extracellular polysaccharides. This interaction culminates in the formation of a highly hydrophilic complex, effectively enabling the rapid inhibition and dispersion of antibiotic-resistant bacterial biofilms, while Fe-TA shows mild photothermal ability to further assist fluffy mature biofilm. In addition, Bi is beneficial to regulate the polarization of macrophages to pro-inflammatory phenotype to further kill escaping biofilm bacteria. In summary, this novel approach offers a promising bionic optimization strategy for treating bacterial-associated infections at all stages through synergetic treatment.

Deciphering the progression of fine-needle aspiration: A bibliometric analysis of thyroid nodule research.

This study aims to dissect the evolution and pivotal shifts in Fine-Needle Aspiration (FNA) research for thyroid nodules over the past 2 decades, focusing on delineating key technological advancements and their impact on clinical practice. A comprehensive bibliometric analysis was conducted on 5418 publications from the Web of Science Core Collection database (2000-2023). Publications were rigorously selected based on their contributions to the advancement of FNA techniques and their influence on thyroid nodule management practices. Our analysis uncovered significant breakthroughs, most notably the incorporation of ultrasound and molecular diagnostics in FNA, which have markedly elevated diagnostic accuracy. A pivotal shift was identified towards minimally invasive post-FNA treatments, such as Radiofrequency Ablation, attributable to these diagnostic advancements. Additionally, the emergence of AI-assisted cytology represents a frontier in precision diagnostics, promising enhanced disease identification. The geographical analysis pinpointed the United States, Italy, and China as key contributors, with the United States leading in both publication volume and citation impact. This bibliometric analysis sheds light on the transformative progression in FNA practices for thyroid nodules, characterized by innovative diagnostic technologies and a trend towards patient-centric treatment approaches. The findings underscore the need for further research into AI integration and global practice standardization. Future explorations should focus on the practical application of these advancements in diverse healthcare settings and their implications for global thyroid nodule management.

Predictive value of positive lymph node ratio in patients with locally advanced gastric remnant cancer.

BACKGROUND: Traditional lymph node stage (N stage) has limitations in advanced gastric remnant cancer (GRC) patients; therefore, establishing a new predictive stage is necessary. AIM: To explore the predictive value of positive lymph node ratio (LNR) according to clinicopathological characteristics and prognosis of locally advanced GRC. METHODS: Seventy-four patients who underwent radical gastrectomy and lymphadenectomy for locally advanced GRC were retrospectively reviewed. The relationship between LNR and clinicopathological characteristics was analyzed. The survival analysis was performed using Kaplan-Meier survival curves and Cox regression model. RESULTS: Number of metastatic LNs, tumor diameter, depth of tumor invasion, Borrmann type, serum tumor biomarkers, and tumor-node-metastasis (TNM) stage were correlated with LNR stage and N stage. Univariate analysis revealed that the factors affecting survival included tumor diameter, anemia, serum tumor biomarkers, vascular or neural invasion, combined resection, LNR stage, N stage, and TNM stage (all P < 0.05). The median survival time for those with LNR0, LNR1, LNR2 and LNR3 stage were 61, 31, 23 and 17 mo, respectively, and the differences were significant (P = 0.000). Anemia, tumor biomarkers and LNR stage were independent prognostic factors for survival in multivariable analysis (all P < 0.05). CONCLUSION: The new LNR stage is uniquely based on number of metastatic LNs, with significant prognostic value for locally advanced GRC, and could better differentiate overall survival, compared with N stage.

Endoscopic Supracerebellar Infratentorial Transpineal Approach for Posterior-Medial Thalamic Lesions: Surgical Technique and Clinical Experience.

BACKGROUND AND OBJECTIVES: Accessing lesions in the posterior-medial thalamus can be challenging because of their deep location and intricate neurovascular anatomy. This study aims to describe the techniques and feasibility of the endoscopic supracerebellar infratentorial transpineal approach for treating posterior-medial thalamus lesions. METHODS: We reviewed and analyzed the clinical outcomes and endoscopic surgical experience of 11 patients with posterior-medial thalamic lesions. The first 4 cases used the endoscopic midline supracerebellar infratentorial transpineal approach, whereas the subsequent 7 cases used the endoscopic contralateral paramedian supracerebellar infratentorial transpineal approach. All cases involved the upward transposition of the pineal gland to access the posterior-medial thalamus. The extent of resection and the endoscopic techniques were the main focus of analysis. Neurological examinations and MRI/computed tomography follow-up were conducted for 3-12 months after surgery. RESULTS: The pathology of the group included 6 gliomas, 1 cavernous malformation, 1 inflammation, 1 melanoma, and 2 hematomas. All 11 patients achieved gross total resection (6 patients, 54.5%) or subtotal resection (5 patients, 45.5%) with no new neurological deficits. Most patients (9 patients, 81.8%) experienced improvement in Karnofsky Performance Status after surgery. Postoperative hydrocephalus occurred in 2 patients (18.2%) and was relieved by endoscopic third ventriculostomy. CONCLUSION: The endoscopic supracerebellar infratentorial transpineal approach is an effective approach for removing posterior-medial thalamic lesions that require access through the third ventricle surfaces of the thalamus. The endoscopic contralateral paramedian supracerebellar infratentorial transpineal approach provides a more superior and lateral view of the posterior-medial thalamic lesions.

Potentiating Immunogenic Cell Death in Cold Tumor with Functional Living Materials of FeAu-Methylene Blue Composites.

Low immunogenicity, absence of tumor-infiltrating lymphocytes and immunosuppressive microenvironment of immune cold tumors are the main bottlenecks leading to unfavorable prognosis. Here, an integrated tumor bioimaging and multimodal therapeutic strategy is developed, which converts immune cold into hot by modulating oxidative stress levels, enhancing photo-killing efficacy, inducing immunogenic cell death and inhibiting the immune checkpoint. On that occasion, the unique tumor microenvironment can be harnessed to biosynthesize in situ self-assembly iron complexes and fluorescent gold nanoclusters from metal ions Fe(II) and Au(III) for active targeting and real-time visualization of the tumors, simultaneously regulating reactive oxygen species levels within tumors via peroxidase-like activity. Furthermore, methylene blue (MB)-mediated photodynamic therapy promotes the release of damage-associated molecular patterns (DAMPs), which acts as in situ tumor vaccine and further induces dendritic cells maturation, augments the infiltration of antitumor T cells and significantly impedes the primary tumor growth and proliferation. More strikingly, by synergizing with the programmed cell death receptor-1 (PD-1) checkpoint inhibitor, the immunosuppressive microenvironment is remodeled and the survival time of model mice is prolonged. In summary, this paradigm utilizes the tumor-specific microenvironment to boost robust and durable systemic antitumor immunity, providing a novel opportunity for precision cancer theranostics.

Analysis of Diffusion-Weighted and T2-Weighted Imaging in the Prediction of Distinct Granulation Patterns of Somatotroph Adenomas.

OBJECTIVE: The heterogeneity of the somatotroph adenomas, especially for sparsely granulated (SG) and densely granulated (DG) subtypes, has attracted great attention in identifying their imaging biomarker. The purpose of the current study was to compare the diagnostic performance of diffusion-weighted and T2-weighted magnetic resonance imaging (MRI) sequences for preoperatively distinguishing the granulation patterns of somatotroph adenomas. METHODS: Thirty-two patients with a clinical diagnosis of somatotroph adenomas from October 2018 to March 2023 were included in this study. Coronal diffusion-weighted imaging (DWI) and T2-weighted MRI sequence data were collected from 3.0T MRI and compared between SG and DG groups. The immunohistochemistry was used to confirm the electron microscopy pathologic subtypes and Ki67 expression levels of somatotroph adenomas postoperatively. RESULTS: Patients in the SG group had significantly higher signal intensity (SI) ratio of DWI (rDWI) (P < 0.001), lower SI ratio of apparent diffusion coefficient (rADC) (P < 0.001), and higher SI ratio of T2-weighted imaging (P = 0.011). The combined diagnosis index of rDWI and rADC had the highest diagnostic efficiency in predicting SG adenomas (sensitivity, 93.3%; specificity, 88.2%; P < 0.001). The rDWI and rADC values had positive and negative correlations with the Ki67 index and tumor maximum diameter, respectively. Lower rADC×103 was an independent predictor for SG adenomas. CONCLUSIONS: Our results indicated that compared with previously used T2-weighted imaging, the DWI sequence, especially the combined diagnosis index of rDWI and rADC, could more efficiently distinguish the granulation patterns of somatotroph adenomas preoperatively.

Implantation of Surgical Paddle Electrodes Using Percutaneous Biportal-Endoscopic Technique for Spinal Cord Stimulation: An Anatomical Feasibility Study in Human Cadavers.

BACKGROUND: Spinal cord stimulation is a technique in which different types of electrodes are placed in the spinal epidural space for neuromodulation. Surgical paddle electrodes (SEs) are usually implanted by a surgeon by performing open surgery with laminectomy. Recent advances in endoscopic spine surgery provide another option for minimally invasive SE implantation. OBJECTIVES: This anatomical study aims to examine the feasibility of implanting SEs in thoracic and cervical spine segments, discussing the specific advantages and disadvantages compared with previously reported methods. STUDY DESIGN: Laboratory study with Institutional Review Board No B2023-056. METHODS: Four fresh adult cadavers (2 women, 2 men) were operated on in this study. The posterior unilateral biportal endoscopic surgical approach, the accessibility to the intraspinal epidural space, and the technical possibilities and limitations of implantation of SEs were evaluated, as well as the surgical duration and complications. RESULTS: All the planned steps of the operation were successfully accomplished in all 4 cadavers. A total of 8 electrodes were successfully implanted through the working portal. Among them, 4 were located in the cervical segment and 4 in the thoracic segment. The proper position of the electrodes was also verified by fluoroscopy. No rupture of dura occurred during the operation. Except for the first cadaver, the duration of surgery did not exceed 1 hour. LIMITATIONS: Anatomical study on human cadavers, the quantity of cadavers, and the steep learning curve. CONCLUSIONS: The results of this anatomical study show that the SEs can be satisfactorily implanted in cervical and thoracic segments using the unilateral biportal endoscopic technique.

RIT1 regulates mitosis and promotes proliferation by interacting with SMC3 and PDS5 in hepatocellular carcinoma.

BACKGROUND: As a small G protein of Ras family, Ras-like-without-CAAX-1 (RIT1) plays a critical role in various tumors. Our previous study has demonstrated the involvement of RIT1 in promoting malignant progression of hepatocellular carcinoma (HCC). However, its underlying mechanism remains unclear. METHODS: Gene set enrichment analysis (GSEA) was conducted in the TCGA LIHC cohort to investigate the underlying biological mechanism of RIT1. Live cell imaging, immunofluorescence (IF) and flow cytometry assays were used to verify biological function of RIT1 in HCC mitosis. Subcutaneous xenografting of human HCC cells in BALB/c nude mice was utilized to assess tumor proliferation in vivo. RNA-seq, co-immunoprecipitation (Co-IP), mass spectrometry analyses, western blot and IF assays were employed to elucidate the mechanisms by which RIT1 regulates mitosis and promotes proliferation in HCC. RESULTS: Our findings demonstrate that RIT1 plays a crucial role in regulating mitosis in HCC. Knockdown of RIT1 disrupts cell division, leading to G2/M phase arrest, mitotic catastrophe, and apoptosis in HCC cells. SMC3 is found to interact with RIT1 and knockdown of SMC3 attenuates the proliferative effects mediated by RIT1 both in vitro and in vivo. Mechanistically, RIT1 protects and maintains SMC3 acetylation by binding to SMC3 and PDS5 during mitosis, thereby promoting rapid cell division and proliferation in HCC. Notably, we have observed an upregulation of SMC3 expression in HCC tissues, which is associated with poor patient survival and promotion of HCC cell proliferation. Furthermore, there is a significant positive correlation between the expression levels of RIT1, SMC3, and PDS5. Importantly, HCC patients with high expression of both RIT1 and SMC3 exhibit worse prognosis compared to those with high RIT1 but low SMC3 expression. CONCLUSIONS: Our findings underscore the crucial role of RIT1 in regulating mitosis in HCC and further demonstrate its potential as a promising therapeutic target for HCC treatment.

Phenotypic and genetic dissection of the contents of important metallic elements in hybrid rice grown in cadmium-contaminated paddy fields.

Rice (Oryza sativa L.) is a staple food that feeds over half of the world's population, and the contents of metallic elements in rice grain play important roles in human nutrition. In this study, the contents of important metallic elements were determined by ICP-OES, and included cadmium (Cd), zinc (Zn), manganese (Mn), copper (Cu), iron (Fe), nickel (Ni), calcium (Ca), and magnesium (Mg) in brown rice, in the first node from the top (Node 1), in the second node from the top (Node 2), and in roots of 55 hybrids and their parental lines. The heritability of metallic element contents (MECs), the general combining ability (GCA) for MEC, and the correlation between MECs in different organs/tissues of hybrids were also analyzed. The results indicated that: (1) there was a positive correlation between the contents of Cd and Zn in nodes and roots, but a negative correlation between the contents of Cd and Zn in brown rice of the hybrids(2) the GCA for MECs can be used to evaluate the ability of the parental lines to improve the metal contents in brown rice of the hybrids(3) the contents of Cd, Zn, Ca, and Mg in brown rice were mainly affected by additive genetic effects(4) the restorer lines R2292 and R2265 can be used to cultivate hybrids with high Zn and low Cd contents in the brown rice.

Endogenous miRNA and K+ Co-Activated Dynamic Assembly of DNA Coacervates for Intracellular miRNA Imaging and Mitochondrial Intervention.

Intracellular dynamic assembly of DNA structures may be beneficial for the development of multifunctional nanoplatforms for the regulation of cell behaviors, providing new strategies for disease diagnosis and intervention. Herein, we propose the dynamic assembly of DNA coacervates in living cells triggered by miRNA-21 and K+, which can be used for both miRNA imaging and mitochondrial intervention. The rationale is that miRNA-21 can trigger the hybridization chain reaction to generate G-quadruplex precursors, and K+ can mediate the assembly of G-quadruplex-based coacervates, allowing the colorimetric detection of miRNA-21 ranging from 10 pM to 10 µM. Moreover, the as-formed DNA coacervates can specifically target mitochondria in MCF-7 breast cancer cells using the MCF-7 cell membrane as delivery carriers, which further act as an anionic shielding to inhibit communication between mitochondria and environments, with a significant inhibitory effect on ATP production and cellular migration behaviors. This work provides an ideal multifunctional nanoplatform for rationally interfering with cellular metabolism and migration behaviors through the dynamic assembly of DNA coacervates mediated by endogenous molecules, which has a large number of potential applications in the biomedical field, especially theranostics for cancer metastasis.

Role of endoscopic third ventriculostomy in patients undergoing resection of pulvinar area lesions: Preliminary clinical results.

BACKGROUND: Patients with pulvinar area lesions may develop hydrocephalus at any stage. The role of endoscopic third ventriculostomy (ETV) in this setting remains unclear. METHOD: We retrospectively enrolled 15 patients with a mean age of 43 years who underwent endoscopic resection of pulvinar area lesions using the supracerebellar infratentorial approach (SCITA). We compared the different modalities of hydrocephalus management and their outcomes. RESULTS: Nine of 15 patients (60.0%) had preoperative obstructive hydrocephalus. Five patients underwent ETV before tumor resection, and none developed postoperative hydrocephalus. Four patients underwent one-stage surgery for tumor removal, and one patient with a polymorphous low-grade neuroepithelial tumor of the young required postoperative ETV. Another patient with diffuse astrocytoma and hydrocephalus underwent concurrent lamina terminalis fenestration and endoscopic resection via the SCITA, which resulted in the resolution of hydrocephalus. The preoperative ETV group had no major postoperative complications, while the non-ETV group had three (0/5 vs. 3/4, P = 0.048). The ETV group also had a shorter intensive care unit stay; however, the difference was not significant (1.2 vs. 2.8; P = 0.188). ETV was effective in alleviating symptoms of postoperative hydrocephalus in patients with midbrain-invading tumors. CONCLUSION: Endoscopic surgery via the SCITA can address both tumor and hydrocephalus issues in some cases but has a higher surgical risk and postoperative hydrocephalus rate. Preoperative ETV can prevent these complications and improve postoperative outcomes.

Endoscopic far-lateral supracerebellar infratentorial approach for resection of dumbbell-shaped trigeminal schwannoma: surgical techniques and preliminary results.

BACKGROUND: Trigeminal schwannomas (TSs) are mostly benign tumors. However, dumbbell-shaped TSs are most challenging for surgeons and pose a high surgical risk. OBJECTIVE: We describe the technique of the purely endoscopic far-lateral supracerebellar infratentorial approach (EFL-SCITA) for removing dumbbell-shaped TSs and further discuss the feasibility of this approach and our experience. METHODS: EFL-SCITA was performed for resection of 5 TSs between January 2020 and March 2023. The entire procedure was performed endoscopically with the goal of total tumor resection. During the operation, the tumor was exposed in close proximity and multiple angles under the endoscope, and the peri-tumor nerves were carefully identified and protected, especially the normal trigeminal fiber bundles around the tumor. RESULTS: All the tumors of 5 patients involved the middle and posterior cranial fossa, of which total removal was achieved in 2 patients and near-total removal in 3 patients. The most common preoperative symptoms were relieved after surgery. Two patients had postoperative mild facial paralysis (House-Brackmann grade II), and 1 patient had abducens palsy; both recovered during the follow-up period. Two patients experienced new postoperative facial hypesthesia, and 1 experienced mastication weakness, which did not recover. There was no tumor recurrence or residual tumor growth during the follow-up period in any of the patients. CONCLUSION: EFL-SCITA is a new and effective alternative for the surgical treatment of TSs. For dumbbell-shaped TSs, this approach provides sufficient surgical field exposure and freedom of operation.

Identification of the potential ferroptosis key genes in lung cancer with bone metastasis.

Background: To identify the potential key genes of ferroptosis in the pathogenesis of lung cancer with bone metastasis (LCBM) by bioinformatics analysis to provide new targets for treating LCBM and an indicator for early monitoring. Methods: We first obtained differentially expressed genes (DEGs) associated with ferroptosis from the Gene Expression Omnibus (GEO) database. MiRWalk 2.0 was used to predict the key microRNAs (miRNAs) and construct related gene-miRNA interaction networks. The functional enrichment analysis of key miRNAs was performed using the miEAA database. Finally, the clinical data of 105 lung cancer patients were retrospectively analyzed, and logistic regression analysis was conducted to assess the relationship between serum alkaline phosphatase (ALP), neuron-specific enolase (NSE), and bone metastasis in lung cancer patients, and a receiver operating characteristic (ROC) curve was drawn. Results: We identified 15 ferroptosis-related genes that were differentially expressed in lung cancer bone metastasis. GO and KEGG enrichment analyses suggested that these genes may affect the oxidative stress response, hypoxia response, rough endoplasmic reticulum, mitochondrial outer membrane, iron-sulfur cluster binding, virus receptor activity, central carbon metabolism in cancer, the interleukin-17 (IL-17) signaling pathway, and other aspects to participate in the occurrence and development of lung cancer bone metastasis. Among the 105 lung cancer patients included in the study, 39 cases had bone metastasis, and the incidence rate was 37.14%. A high Eastern Cooperative Oncology Group (ECOG) score and serum ALP and NSE overexpression were associated with bone metastasis in patients with lung cancer. By assessing the risk of bone metastasis in patients with lung cancer, we found that the Area Under Curves (AUCs) of serum ALP and NSE alone and combined were >0.70. Conclusions: The differentially expressed ferroptosis-related genes and predicted miRNA regulatory network in lung cancer bone metastasis and the related functional enrichment analysis provide new targets for the treatment of lung cancer bone metastasis. At the same time, from a serological perspective, it was found that early monitoring of serum ALP and NSE expression in patients with lung cancer could be considered to assess the risk of bone metastasis in the future.

HNF4A-BAP31-VDAC1 axis synchronously regulates cell proliferation and ferroptosis in gastric cancer.

B cell receptor associated protein 31 (BAP31) is closely associated with tumor progression, while the role and mechanism of BAP31 in gastric cancer (GC) remains unknown. This study explored that BAP31 was upregulated in GC tissues and high expression indicated poor survival of GC patients. BAP31 knockdown inhibited cell growth and induced G1/S arrest. Moreover, BAP31 attenuation increased the lipid peroxidation level of the membrane and facilitated cellular ferroptosis. Mechanistically, BAP31 regulated cell proliferation and ferroptosis by directly binding to VDAC1 and affected VDAC1 oligomerization and polyubiquitination. HNF4A was bound to BAP31 at the promoter and increased its transcription. Furthermore, knockdown of BAP31 inclined to make GC cells vulnerable to 5-FU and ferroptosis inducer, erastin, in vivo and in vitro. Our work suggests that BAP31 may serve as prognostic factor for gastric cancer and act as potential therapeutic strategy for gastric cancer.