Primate-Specific DAZ Regulates Translation of Cell Proliferation-Related mRNAs and is Essential for Maintenance of Spermatogonia.

Primate-specific DAZ (deleted in azoospermia) has evolved in the azoospermia factor c (AZFc) locus on the Y chromosome. Loss of DAZ is associated with azoospermia in patients with deletion of the AZFc region (AZFc_del). However, the molecular mechanisms of DAZ in spermatogenesis remain uncertain. In this study, the molecular mechanism of DAZ is identified, which is unknown since it is identified 40 years ago because of the lack of a suitable model. Using clinical samples and cell models, it is shown that DAZ plays an important role in spermatogenesis and that loss of DAZ is associated with defective proliferation of c-KIT-positive spermatogonia in patients with AZFc_del. Mechanistically, it is shown that knockdown of DAZ significantly downregulated global translation and subsequently decreased cell proliferation. Furthermore, DAZ interacted with PABPC1 via the DAZ repeat domain to regulate global translation. DAZ targeted mRNAs that are involved in cell proliferation and cell cycle phase transition. These findings indicate that DAZ is a master translational regulator and essential for the maintenance of spermatogonia. Loss of DAZ may result in defective proliferation of c-KIT-positive spermatogonia and spermatogenic failure.

CDDO, an Anti-Inflammatory and Antioxidant Compound, Attenuates Vasospasm and Neuronal Cell Apoptosis in Rats Subjected to Experimental Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) is a type of stroke caused by bleeding into the subarachnoid space. SAH is a medical emergency and requires prompt treatment to prevent complications such as seizures, stroke, or other brain damage. Treatment options may include surgery, medication, or a combination of both. 2-Cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO), a compound with anti-inflammatory and antioxidant properties, is currently being investigated as a potential treatment for various diseases, including chronic kidney disease and pulmonary arterial hypertension. In this study, the effects of CDDO on rats subjected to SAH were evaluated. Male Sprague-Dawley rats were divided into four groups (n = 6/group): (1) control group, (2) SAH group, (3) SAH + low-dose CDDO (10 mg/kg injected into the subarachnoid space at 24 h after SAH) group, and (4) SAH + high-dose CDDO (20 mg/kg) group. CDDO improved SAH-induced poor neurological outcomes and reduced vasospasm in the basal artery following SAH. It also decreased the SAH-induced expression of proinflammatory cytokines such as TNF-α, IL-1ß, and IL-6 in both the cerebrospinal fluid and serum samples as determined by ELISA. A Western blot analysis confirmed an increase in the p-NF-κB protein level after SAH, but it was significantly decreased with CDDO intervention. Immunofluorescence staining highlighted the proliferation of microglia and astrocytes as well as apoptosis of the neuronal cells after SAH, and treatment with CDDO markedly reduced the proliferation of these glial cells and apoptosis of the neuronal cells. The early administration of CDDO after SAH may effectively mitigate neuronal apoptosis and vasospasm by suppressing inflammation.

Verbascoside inhibits oral squamous cell carcinoma cell proliferation, migration, and invasion by the methyltransferase 3-mediated microRNA-31-5p/homeodomain interacting protein kinase 2 axis.

OBJECTIVE: The study aimed to investigate the effects of verbascoside on oral squamous cell carcinoma (OSCC) cellular behaviors and underlying molecular mechanisms. DESIGN: For this purpose, SCC9 and UM1 cell lines were treated with verbascoside, and their biological behaviors, including proliferation, migration, and invasion, were evaluated using cell counting kit-8, 5-Ethynyl-2'-deoxyuridine, and Transwell assays. The expression of methyltransferase-3 (METTL3), microRNA (miR)- 31-5p, and homeodomain interacting protein kinase-2 (HIPK2) were examined using quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between METTL3 and miR-31-5p was evaluated by RNA immunoprecipitation and methylated RNA immunoprecipitation, while the interaction between miR-31-5p and HIPK2 was evaluated by dual-luciferase reporter analysis. RESULTS: The results indicated inhibition of OSCC cell proliferation, migration, and invasion post verbascoside treatment. Similarly, METTL3 was upregulated in OSCC cells and was inhibited post-verbascoside treatment. Overexpressing METTL3 promoted the cellular processes. Moreover, miR-31-5p was upregulated in OSCC cells, where METTL3 facilitated the processing of miR-31-5p in an N6-methyladenosine (m6A)-dependent manner. The HIPK2 served as miR-31-5p target, where overexpressing miR-31-5p or HIPK2 knockdown reversed the suppression of verbascoside-induced biological behaviors. CONCLUSIONS: Verbascoside inhibited the progression of OSCC by inhibiting the METTL3-regulated miR-31-5p/HIPK2 axis. These findings suggested that verbascoside might be an effective drug for OSCC therapy.

Characterization of gene regulatory networks underlying key properties in human hematopoietic stem cell ontogeny.

Human hematopoiesis starts at early yolk sac and undergoes site- and stage-specific changes over development. The intrinsic mechanism underlying property changes in hematopoiesis ontogeny remains poorly understood. Here, we analyzed single-cell transcriptome of human primary hematopoietic stem/progenitor cells (HSPCs) at different developmental stages, including yolk-sac (YS), AGM, fetal liver (FL), umbilical cord blood (UCB) and adult peripheral blood (PB) mobilized HSPCs. These stage-specific HSPCs display differential intrinsic properties, such as metabolism, self-renewal, differentiating potentialities etc. We then generated highly co-related gene regulatory network (GRNs) modules underlying the differential HSC key properties. Particularly, we identified GRNs and key regulators controlling lymphoid potentiality, self-renewal as well as aerobic respiration in human HSCs. Introducing selected regulators promotes key HSC functions in HSPCs derived from human pluripotent stem cells. Therefore, GRNs underlying key intrinsic properties of human HSCs provide a valuable guide to generate fully functional HSCs in vitro.

Health care-associated infections after surgical treatment of ruptured intracranial aneurysms.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) is catastrophic, and microsurgery for ruptured intracranial aneurysms is one of the preventive modalities for rebleeding. However, patients remain at high risk of medical morbidities after surgery, one of the most important of which is health care-associated infections (HAIs). We analyzed the incidence and risk factors of HAIs, as well as their association with the outcomes after surgical treatment of ruptured aneurysms. METHODS: We retrospectively enrolled 607 patients with SAH who had undergone surgery for intracranial aneurysms. Information was retrieved from the database using codes of the International Classification of Diseases, Ninth Revision, Clinical Modification. RESULTS: Of the 607 patients, 203 were male and 404 were female. HAIs occurred in 113 patients, accounting for 18.6 % of the population. The independent risk factors for HAIs included age ((p = 0.035), hypertension ((p = 0.042), convulsion ((p = 0.023), external ventricular drain ((p = 0.035), ventricular shunt ((p = 0.033), and blood transfusion ((p = 0.001). The mean length of hospital stay was 25.3 ± 18.2 and 18.8 ± 15.3 days for patients with and without HAIs, respectively ((p = 0.001). The in-hospital mortality rates were 11.5 % in the HAIs group, and 14.0 % in the non-HAIs group ((p = 0.490). CONCLUSION: HAIs are a frequent complication in patients with SAH who underwent surgery for ruptured intracranial aneurysms. The length of hospital stay is remarkably longer for patients with HAIs, and to recognize and reduce the modifiable risks should be implemented to improve the quality of patient care.

Infection may play an important role in the pathogenesis of alveolar osteonecrosis following facial herpes zoster: a case report and literature review.

BACKGROUND: Herpes zoster (HZ) is one of the most common skin diseases caused by viruses. Facial HZ develops when the varicella-zoster virus affects the trigeminal nerve, and alveolar osteonecrosis is a rare complication. However, the exact pathogenesis of postherpetic alveolar osteonecrosis remains unclear. CASE DESCRIPTION: We encountered a patient who presented to the dermatology clinic with facial HZ and tooth exfoliation in the upper right jaw, and panoramic radiography revealed decreased bone density and poor alveolar socket healing in his right maxilla. Biopsy of the alveolar process revealed fragments of nonvital lamellar bone, which were devoid of osteoblasts and osteocytes and were surrounded by numerous neutrophils and bacterial aggregates. Thus, the diagnosis of alveolar osteonecrosis following facial HZ was confirmed. He then underwent resection of the osteonecrotic tissue. The pathological findings of postoperative tissue were similar to those of previous biopsies. Varicella-zoster virus and multiple types of bacteria were detected through next-generation sequencing, and the species of bacteria were consistent with the results of bacterial culture. Antibiotics and valaciclovir were administered during the perioperative period. The patient showed good recovery at the 9-month follow-up. CONCLUSIONS: The coexistence of bacterial and viral infection may play an important role in the pathogenesis of alveolar osteonecrosis following HZ. To our knowledge, we are the first to directly explore microbial pathogens in a case of postherpetic alveolar osteonecrosis through next-generation sequencing and bacterial culture. We recommend that oral examinations be carefully conducted for patients who are diagnosed with facial HZ, even if their facial rashes have faded away. We suggest that a prolonged and full-dose antiviral therapy course may be beneficial for the treatment of facial HZ with intraoral lesions. The implementation of dental preventive measures should be considered for patients with facial HZ. The application of antibiotics and excision of necrotic bone may reduce the abundance of bacteria in lesions and improve wound healing.

Clinical risk prediction model and external validation of positive surgical margin in laparoscopic radical prostatectomy based on MRI lesion location.

OBJECTIVE: To clarify the composition of lesions in different magnetic resonance imaging (MRI) partitions of positive surgical margins (PSM) after laparoscopic radical prostatectomy, explore the influence of lesion location on PSM, and construct a clinical prediction model to predict the risk of PSM. MATERIALS AND METHODS: This retrospective cohort study included 309 patients who underwent laparoscopic radical prostatectomy from 2018 to 2021 in our center was performed. 129 patients who met the same criteria from January to September 2022 were external validation cohorts. RESULTS: The incidence of PSM in transition zone (TZ) lesions was higher than that in peripheral zone (PZ) lesions. The incidence of PSM in the middle PZ was lower than that in other regions. Prostate specific antigen (PSA), clinical T-stage, the number of positive cores, international society of urological pathology (ISUP) grade (biopsy), MRI lesion location, extracapsular extension, seminal vesicle invasion (SVI), pseudo-capsule invasion (PCI), long diameter of lesions, lesion volume, lesion volume ratio, PSA density were related to PSM. MRI lesion location and PCI were independent risk factors for PSM. Least absolute shrinkage and selection operator (LASSO) regression was used to construct a clinical prediction model for PSM, including five variables: the number of positive cores, SVI, MRI lesion location, long diameter of lesions, and PSA. CONCLUSION: The positive rate of surgical margin in middle PZ was significantly lower than that in other regions, and MRI lesion location was an independent risk factor for PSM.

MYC overexpression in natural killer cell lymphoma: prognostic and therapeutic implications.

The current clinical management of Extranodal NK/T-cell lymphoma (ENKTL) primarily depends on conventional chemotherapy and radiotherapy, underscoring the need for innovative therapeutic strategies. This study explores the clinical significance and therapeutic implication of c-MYC (MYC) in ENKTL. Initially, we identified MYC protein overexpression in approximately 75% of cases within a large cohort of 111 patients. MYC overexpression was strongly correlated with lymphoma cell proliferation and poor clinical outcomes. Intriguingly, integrating MYC expression into the PINK-E prognostic model significantly enhanced its predictive power. Subsequently, we implemented MYC knockdown (KD) in NK malignancy cell lines with MYC overexpression, resulting in significant viability reduction. RNA-sequencing (RNA-seq) used to determine MYC function revealed a high overlap with canonical MYC-regulated genes and enrichment in metabolism and cell cycle regulation. Integrative analysis of the RNA-seq data upon MYC KD with gene expression profiles of primary ENKTL cases identified a subset of genes closely associated with MYC overexpression. Among these, CDK4 emerged as a potential therapeutic target, and its inhibition not only abrogated MYC function but also decreased MYC expression in NK malignancy cells. Furthermore, the clinical-grade CDK4/6 inhibitor palbociclib exhibited a potent anti-tumor effect in xenograft mouse models, especially when combined with gemcitabine. In summary, our study firmly establishes MYC as an oncogene with prognostic significance in ENKTL and highlights CDK4 inhibition as a promising therapeutic strategy for treating ENKTL with MYC overexpression.

A fluorescence detection method for postharvest tomato epidermal defects based on improved YOLOv5m.

BACKGROUND: Tomato quality visual grading is greatly affected by the problems of smooth skin, uneven illumination and invisible defects that are difficult to identify. The realization of intelligent detection of postharvest epidermal defects is conducive to further improving the economic value of postharvest tomatoes. RESULTS: An image acquisition device that utilizes fluorescence technology has been designed to capture a dataset of tomato skin defects, encompassing categories such as rot defects, crack defects and imperceptible defects. The YOLOv5m model was improved by introducing Convolutional Block Attention Module and replacing part of the convolution kernels in the backbone network with Switchable Atrous Convolution. The results of comparison experiments and ablation experiments show that the Precision, Recall and mean Average Precision of the improved YOLOv5m model were 89.93%, 82.33% and 87.57%, which are higher than YOLOv5m, Faster R-CNN and YOLOv7, and the average detection time was reduced by 47.04 ms picture-1. CONCLUSION: The present study utilizes fluorescence imaging and an improved YOLOv5m model to detect tomato epidermal defects, resulting in better identification of imperceptible defects and detection of multiple categories of defects. This provides strong technical support for intelligent detection and quality grading of tomatoes. © 2024 Society of Chemical Industry.

Advancements in Uric Acid Stone Detection: Integrating Deep Learning with CT Imaging and Clinical Assessments in the Upper Urinary Tract.

The incidence of urinary tract stones is increasing worldwide, with a notably high recurrence rate. Among upper urinary tract stones, a significant proportion comprises uric acid stones. This study aims to rapid and reliable identification of uric acid stones in the upper urethra by gathering comprehensive biochemical profiles, urinalysis, and CT scan data from 276 patients diagnosed with kidney and ureteral stones. Leveraging machine learning techniques, the goal is to establish multiple predictive models that can accurately identify uric acid stones.

KIF5B plays important roles in dendritic spine plasticity and dendritic localization of PSD95 and FMRP in the mouse cortex in vivo.

Kinesin 1 (KIF5) is one major type of motor protein in neurons, but its members' function in the intact brain remains less studied. Using in vivo two-photon imaging, we find that conditional knockout of Kif5b (KIF5B cKO) in CaMKIIα-Cre-expressing neurons shows heightened turnover and lower stability of dendritic spines in layer 2/3 pyramidal neurons with reduced spine postsynaptic density protein 95 acquisition in the mouse cortex. Furthermore, the RNA-binding protein fragile X mental retardation protein (FMRP) is translocated to the proximity of newly formed spines several hours before the spine formation events in vivo in control mice, but this preceding transport of FMRP is abolished in KIF5B cKO mice. We further find that FMRP is localized closer to newly formed spines after fear extinction, but this learning-dependent localization is disrupted in KIF5B cKO mice. Our findings provide the crucial in vivo evidence that KIF5B is involved in the dendritic targeting of synaptic proteins that underlies dendritic spine plasticity.

Deep learning-based bronchial tree-guided semi-automatic segmentation of pulmonary segments in computed tomography images.

Background: Pulmonary segments are valuable because they can provide more precise localization and intricate details of lung cancer than lung lobes. With advances in precision therapy, there is an increasing demand for the identification and visualization of pulmonary segments in computed tomography (CT) images to aid in the precise treatment of lung cancer. This study aimed to integrate multiple deep-learning models to accurately segment pulmonary segments in CT images using a bronchial tree (BT)-based approach. Methods: The proposed segmentation method for pulmonary segments using the BT-based approach comprised the following five essential steps: (I) segmentation of the lung using a U-Net (R231) (public access) model; (II) segmentation of the lobes using a V-Net (self-developed) model; (III) segmentation of the airway using a combination of a differential geometric approach method and a BronchiNet (public access) model; (IV) labeling of the BT branches based on anatomical position; and (V) segmentation of the pulmonary segments based on the distance of each voxel to the labeled BT branches. This five-step process was applied to 14 high-resolution breath-hold CT images and compared against manual segmentations for evaluation. Results: For the lung segmentation, the lung mask had a mean dice similarity coefficient (DSC) of 0.98±0.03. For the lobe segmentation, the V-Net model had a mean DSC of 0.94±0.06. For the airway segmentation, the average total length of the segmented airway trees per image scan was 1,902.8±502.1 mm, and the average number of the maximum airway tree generations was 8.5±1.3. For the segmentation of the pulmonary segments, the proposed method had a DSC of 0.73±0.11 and a mean surface distance of 6.1±2.9 mm. Conclusions: This study demonstrated the feasibility of combining multiple deep-learning models for the auxiliary segmentation of pulmonary segments on CT images using a BT-based approach. The results highlighted the potential of the BT-based method for the semi-automatic segmentation of the pulmonary segment.

Clinical significance of serum high sensitive C-reactive protein/albumin ratio in primary prostate biopsy.

Objective: The purpose of this study was to investigate the clinical significance of serum high sensitive C-reactive protein/albumin ratio in primary prostate biopsy. Methods: Retrospective analysis was done on the clinical data of 1679 patients who had their first transrectal or perineal prostate biopsy at our situation from 2010 to 2018. Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) were the pathologic diagnoses in 819 and 860 cases, respectively. A comparison was made between the HAR differences between PCa and BPH patients as well as the positive prostate biopsy rate differences between groups with increased and normal HAR. The results of the prostate biopsy were examined using logistic regression, and a model for predicting prostate cancer was created. The receiver characteristic curve (ROC) was used to determine the model's prediction effectiveness. The clinical models integrated into HAR were evaluated for their potential to increase classification efficacy using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). According to the Gleason score (GS) categorization system, prostate cancer patients were separated into low, middle, and high GS groups. The differences in HAR between the various groups were then compared. The prevalence of high GSPCa and metastatic PCa in normal populations and the prevalence of higher HAR in prostate cancer patients were compared using the chi-square test. Result: Patients with PCa had a median HAR (upper quartile to lower quartile) of 0.0379 (10-3), patients with BPH had a median HAR (0.0137 (10-3)), and the difference was statistically significant (p<0.05). Patients with increased HAR and the normal group, respectively, had positive prostate biopsy rates of 52% (435/839)and 46% (384/840), and the difference was statistically significant (p<0.05). Logistic regression analysis showed that HAR (OR=3.391, 95%CI 2.082 ~ 4.977, P < 0.05), PSA density (PSAD) (OR=7.248, 95%CI 5.005 ~ 10.495, P < 0.05) and age (OR=1.076, 95%CI 1.056 ~ 1.096, P < 0.05) was an independent predictor of prostate biopsy results. Two prediction models are built: a clinical model based on age and PSAD, and a prediction model that adds HAR to the clinical model. The two models' ROC had area under the curves (AUC) of 0.814 (95%CI 0.78-0.83) and 0.815 (95%CI 0.79-0.84), respectively. When compared to a single blood total PSA (tPSA) with an AUC of 0.746 (95%CI 0.718-0.774), they were all superior. Nevertheless, there was no statistically significant difference (p<0.05) between the two models. We assessed the prediction model integrated into HAR's capacity to increase classification efficiency using NRI and IDI, and we discovered that NRI>0, IDI>0, and the difference was statistically significant (P>0.05).There was a statistically significant difference in HAR between various GS groups for individuals who had prostate cancer as a consequence of biopsy (p<0.05). The incidence of high GS and metastatic patients was statistically significantly greater (p<0.05) in the HAR elevated group (90.1%and 39.3%, respectively) than in the HAR normal group (84.4% and 12.0%). Conclusion: Prostate biopsy results that were positive were impacted by HAR, an independent factor that increased with the rate of PCa discovery. Patients with elevated HAR had a greater risk of high GS as well as metastatic PCa among those with recently diagnosed prostate cancer through prostate biopsy.

Large-scale generation of IL-12 secreting macrophages from human pluripotent stem cells for cancer therapy.

Genetically engineered macrophages (GEMs) have emerged as an appealing strategy to treat cancers, but they are largely impeded by the cell availability and technical challenges in gene transfer. Here, we develop an efficient approach to generate large-scale macrophages from human induced pluripotent stem cells (hiPSCs). Starting with 1 T150 dish of 106 hiPSCs, more than 109 mature macrophages (iMacs) could be generated within 1 month. The generated iMacs exhibit typical macrophage properties such as phagocytosis and polarization. We then generate hiPSCs integrated with an IL-12 expression cassette in the AAVS1 locus to produce iMacs secreting IL-12, a strong proimmunity cytokine. hiPSC-derived iMacs_IL-12 prevent cytotoxic T cell exhaustion and activate T cells to kill different cancer cells. Furthermore, iMacs_IL-12 display strong antitumor effects in a T cell-dependent manner in subcutaneously or systemically xenografted mice of human lung cancer. Therefore, we provide an off-the-shelf strategy to produce large-scale GEMs for cancer therapy.

Structure Guided Discovery of Novel Pan Metallo-ß-Lactamase Inhibitors with Improved Gram-Negative Bacterial Cell Penetration.

The use of ß-lactam (BL) and ß-lactamase inhibitor combination to overcome BL antibiotic resistance has been validated through clinically approved drug products. However, unmet medical needs still exist for the treatment of infections caused by Gram-negative (GN) bacteria expressing metallo-ß-lactamases. Previously, we reported our effort to discover pan inhibitors of three main families in this class: IMP, VIM, and NDM. Herein, we describe our work to improve the GN coverage spectrum in combination with imipenem and relebactam. This was achieved through structure- and property-based optimization to tackle the GN cell penetration and efflux challenges. A significant discovery was made that inhibition of both VIM alleles, VIM-1 and VIM-2, is essential for broad GN coverage, especially against VIM-producing P. aeruginosa. In addition, pharmacokinetics and nonclinical safety profiles were investigated for select compounds. Key findings from this drug discovery campaign laid the foundation for further lead optimization toward identification of preclinical candidates.

Cost-effectiveness analysis of different anesthesia strategies for transperineal MRI/US fusion prostate biopsy.

ABSTRACT: This study aims to conduct a cost-effectiveness analysis of three different anesthesia strategies, namely chatting while under local anesthesia (Chat-LA), total intravenous anesthesia (TIVA), and general anesthesia with laryngeal mask airway (GA-LMA), employed in transperineal magnetic resonance imaging (MRI)/ultrasound (US) fusion prostate biopsy (TP-MUF-PB). A retrospective study was conducted involving 1202 patients who underwent TP-MUF-PB from June 2016 to April 2023 at The First Affiliated Hospital of Soochow University (Suzhou, China). Clinical data and outcomes, including total costs, complications, and quality-adjusted life years (QALYs), were compared. Probability sensitivity and subgroup analyses were also performed. Chat-LA was found to be the most cost-effective option, outperforming both TIVA and GA-LMA. However, subgroup analyses revealed that in younger patients (under 65 years old) and those with smaller prostate volumes (<40 ml), TIVA emerged as a more cost-effective strategy. While Chat-LA may generally be the most cost-effective and safer anesthesia method for TP-MUF-PB, personalization of anesthesia strategies is crucial, considering specific patient demographics such as age and prostate volume.

Transformable Supramolecular Self-Assembled Peptides for Cascade Self-Enhanced Ferroptosis Primed Cancer Immunotherapy.

Immunotherapy has received widespread attention for its effective and long-term tumor-eliminating ability. However, for immunogenic "cold" tumors, such as prostate cancer (PCa), the low immunogenicity of the tumor itself is a serious obstacle to efficacy. Here, this work reports a strategy to enhance PCa immunogenicity by triggering cascade self-enhanced ferroptosis in tumor cells, turning the tumor from "cold" to "hot". This work develops a transformable self-assembled peptide TEP-FFG-CRApY with alkaline phosphatase (ALP) responsiveness and glutathione peroxidase 4 (GPX4) protein targeting. TEP-FFG-CRApY self-assembles into nanoparticles under aqueous conditions and transforms into nanofibers in response to ALP during endosome/lysosome uptake into tumor cells, promoting lysosomal membrane permeabilization (LMP). On the one hand, the released TEP-FFG-CRAY nanofibers target GPX4 and selectively degrade the GPX4 protein under the light irradiation, inducing ferroptosis; on the other hand, the large amount of leaked Fe2+ further cascade to amplify the ferroptosis through the Fenton reaction. TEP-FFG-CRApY-induced immunogenic ferroptosis improves tumor cell immunogenicity by promoting the maturation of dendritic cells (DCs) and increasing intratumor T-cell infiltration. More importantly, recovered T cells further enhance ferroptosis by secreting large amounts of interferon-gamma (IFN-γ). This work provides a novel strategy for the molecular design of synergistic molecularly targeted therapy for immunogenic "cold" tumors.

Utilizing the International Normalized Ratio-Platelet Index for Predicting Hospital Outcomes After Spontaneous Supratentorial Intracerebral Hemorrhage.

OBJECTIVE: Spontaneous intracerebral hemorrhage (ICH) poses a public health issue due to its elevated mortality rates. The International Normalized Ratio-platelet index (INR-Plt index) has recently been recognized as a predictive factor for liver disease progression. The potential of applying the INR-Plt index in forecasting ICH prognosis presents an intriguing subject. This study endeavors to examine the correlation between the INR-Plt index and hospital outcomes in patients with spontaneous supratentorial ICH. METHODS: A retrospective examination of 283 adult ICH patients was undertaken. The INR-Plt index was computed using the formula: [INR/platelet counts (1000/µL)] × 100. The clinical outcomes evaluated consisted of mortality rates and the Modified Rankin Scale (mRS) at discharge. An unfavorable outcome was defined as an mRS score from 4 to 6. RESULTS: The study found a significant correlation between the INR-Plt index and hospital mortality (odds ratio: 4.31, 95% CI: 1.07-17.31, P = 0.04). There was a 43% rise in mortality risk for every 0.1 unit increase in the INR-Plt index. Kaplan-Meier survival curves illustrated a considerably lower survival rate at discharge for patients with an INR-Plt index >0.8 (log-rank test: P = 0.047). Regarding unfavorable outcomes, the INR-Plt index was not a significant factor according to logistic regression analyses. CONCLUSIONS: The INR-Plt index is a predictor of hospital mortality in patients with spontaneous supratentorial ICH. A higher INR-Plt index value is associated with an increased risk of mortality, underlining the potential usefulness of this composite index in guiding clinical decision-making and enabling risk stratification.