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The primary cause of mortality among patients with cancer is the progression of the tumor, better known as cancer invasion and metastasis. Cancer progression involves a series of biologically important steps in which the cross-talk between cancer cells and the cells in the surrounding environment is positioned as an important issue. Notably, angiogenesis is a key tumorigenic phenomenon for cancer progression. Cancer-related extracellular vesicles (EVs) commonly contribute to the modulation of a microenvironment favorable to cancer cells through their function of cell-to-cell communication. Vascular-related cells such as endothelial cells (ECs) and platelets activated by cancer cells and cancer-derived EVs develop procoagulant and proinflammatory statuses, which help excite the tumor environment, and play major roles in tumor progression, including in tumor extravasation, tumor cell microthrombi formation, platelet aggregation, and metastasis. In particular, cancer-derived EVs influence ECs, which then play multiple roles such as contributing to tumor angiogenesis, loss of endothelial vascular barrier by binding to ECs, and the subsequent endothelial-to-mesenchymal transition, i.e., extracellular matrix remodeling. Thus, cell-to-cell communication between cancer cells and ECs via EVs may be an important target for controlling cancer progression. This review describes the current knowledge regarding the involvement of EVs, especially exosomes derived from cancer cells, in EC-related cancer progression.

Tumor progression involves a series of biologically important steps in which the crosstalk between cancer cells and the surrounding environment is an important issue. Angiogenesis is a key tumorigenic phenomenon for cancer progression. Tumor-related extracellular vesicles (EVs) modulate the tumor microenvironment (TME) through cell-to-cell communication. Tumor cells in a hypoxic TME release more EVs than cells in a normoxic environment due to uncontrollable tumor proliferation. Tumor-derived EVs in the TME influence endothelial cells (ECs), which then play multiple roles, contributing to tumor angiogenesis, loss of the endothelial vascular barrier by binding to ECs, and subsequent endothelial-to-mesenchymal transition. In contrast, they also indirectly induce tumor angiogenesis through the phenotype switching of various cells into cancer-associated fibroblasts, the activation of tumor-associated ECs and platelets, and remodeling of the extracellular matrix. Here, we review current knowledge regarding the involvement of EVs in tumor vascular-related cancer progression.

BackgroundLittle is known about whether patients with complete congenital stationary night blindness (CSNB) maintain visual function throughout their lifetime. The purpose of this report was to describe clinical and genetic features of an elderly female patient with complete CSNB that we followed for 5 years.MethodsMolecular genetic analysis using whole-exome sequencing (WES) was performed to detect disease-causing variants. We performed a comprehensive ophthalmic examination including full-field electroretinography (ERG).ResultsIn the patient, WES identified two novel variants (c.1034delT; p.Phe345SerfsTer16 and c.1880T>A; p.Met627Lys) in the TRPM1 gene. Her unaffected daughter has one of the variants. The patient reported that her visual acuity has remained unchanged since elementary school. At the age of 68 years old, fundus and fundus autofluorescence imaging showed no remarkable findings except for mild myopic changes. Goldmann perimetry showed preserved visual fields with all V-4e, I-4e, I-3e and I-2e isopters. Optical coherence tomography demonstrated preserved retinal thickness and lamination. Rod ERG showed no response; bright-flash ERG showed an electronegative configuration with minimally reduced a-waves, and cone and 30-Hz flicker ERG showed minimally reduced responses. Overall, the ERG findings of ON bipolar pathway dysfunction were consistent with complete CSNB.ConclusionsThis is the oldest reported patient with complete CSNB and biallelic TRPM1 variants. Our ophthalmic findings suggest that some patients with TRPM1-related CSNB may exhibit preserved retinal function later in life.

INTRODUCTION: Abdominal compartment syndrome (ACS) is a serious complication that can occur after endovascular aneurysm repair (EVAR) for ruptured abdominal aortic aneurysm (rAAA). Prompt recognition and appropriate management are crucial to improve patient outcomes.CASE PRESENTATION: An octogenarian with an 11-cm rAAA underwent emergent EVAR due to cardiovascular instability. Postoperatively, the patient developed ACS, necessitating open abdominal management (OAM) due to intestinal edema and retroperitoneal hematoma. Despite multiple surgical interventions, including aneurysmorrhaphy and removal of retroperitoneal hematoma, the patient experienced prolonged difficulty in abdominal closure. The following procedures were attempted for abdominal closure: 1) Dissection of skin and subcutaneous tissues from the rectus sheath on both sides. 2) Release of the external oblique muscle from the anterior layer of the rectus by longitudinally cutting the superficial fascia. 3) Closure of both rectus sheaths with horizontal mattress sutures and negative pressure wound therapy (NPWT). On POD 20, fluid accumulation from bleeding complicated abdominal closure. However, the abdominal wall was successfully closed by achieving hemostasis and using NPWT. Despite these efforts, the patient developed multiple organ failure, including respiratory and renal failure. Sepsis ultimately led to the patient's death on the 80th POD.CONCLUSIONS: ACS following EVAR for rAAA significantly impacts patient prognosis. Specific techniques for abdominal closure, as described in this case, may help minimize the duration of OAM in challenging cases.

INTRODUCTION: Thromboangiitis obliterans (TAO) has become increasingly uncommon in Japan due to declining smoking prevalence. However, in advanced cases with severely compromised distal vasculature, achieving durable limb salvage remains a formidable surgical challenge.CASE PRESENTATION: A 51-year-old man with a 12-year history of TAO presented with rest pain and a necrotic ulcer on the 2nd toe. He had recently ceased smoking after a 31-year history. Imaging demonstrated complete occlusion of the popliteal and tibial arteries, with foot perfusion reliant on corkscrew collaterals. The ankle-brachial index was 0.43, and skin perfusion pressure (SPP) was critically low. A severely diseased plantar artery was identified as a potential distal target. Given the high risk of graft failure, a hybrid strategy combining in situ bypass and surgical distal venous arterialization (DVA) was preoperatively planned. To mitigate perioperative vasospasm, a lumbar sympathetic block was administered 1 week prior to surgery. An in situ bypass using the ipsilateral great saphenous vein was constructed from the superficial femoral artery to the plantar artery. DVA was established via retrograde puncture of the plantar vein, balloon angioplasty for valve sites, and end-to-side anastomosis to the bypass graft. Early duplex ultrasonography revealed anastomotic stenosis at the DVA site as well as stenosis at valve sites, both of which were successfully managed with a single endovascular procedure. The toe stump healed completely within 3 months. The graft remained patent for 2 years, and SPP was preserved even after graft occlusion. Notably, graft failure coincided with DVA occlusion, suggesting its critical role in maintaining flow. At 42 months postoperatively, the patient remained ulcer-free with favorable perfusion, pain-free ambulation, and full return to work.CONCLUSIONS: Preoperatively planned surgical DVA, in conjunction with sympathetic modulation and timely postoperative intervention, may offer a durable limb salvage strategy in advanced TAO with limited distal targets.

Nucleic acid drugs, such as siRNAs, antisense oligonucleotides, and miRNAs, exert their therapeutic effects by causing genetic changes in cells. However, there are various limitations in their delivery to target organs and cells, making their application to cancer treatment difficult. Extracellular vesicles (EVs) are lipid bilayer particles that are released from most cells, are stable in the blood, and have low immunogenicity. Methods using EVs to deliver nucleic acid drugs to target organs are rapidly being developed that take advantage of these properties. There are two main methods for loading nucleic acid drugs into EVs. One is to genetically engineer the parent cell and load the target gene into the EV, and the other is to isolate EVs and then load them with the nucleic acid drug. Target organ delivery methods include passive targeting using the enhanced permeation and retention effect of EVs and active targeting in which EVs are modified with antibodies, peptides, or aptamers to enhance their accumulation in tumors. In this review, we summarize the advantages of EVs as a drug delivery system for nucleic acid drugs, the methods of loading nucleic acid drugs into EVs, and the targeting of EVs to target organs.

Objectives: Patients with chronic limb-threatening ischemia (CLTI) represent a high-risk cohort for cardiac surgery due to the systemic atherosclerotic burden and frailty. This study aimed to evaluate the short- and mid-term prognoses of CLTI patients undergoing open cardiac surgery and to assess the prognostic utility of four risk scoring systems: Japan SCORE, SPINACH SCORE, Clinical Frailty Scale (CFS), and Geriatric Nutritional Risk Index (GNRI). Methods: We retrospectively analyzed 44 patients with CLTI who underwent open cardiac surgery between 2014 and 2023. Thirty-day and 1-year mortality were assessed. Patients were stratified using ROC-derived cutoffs for each scoring system. Kaplan–Meier survival curves and time-dependent ROC analyses were used to evaluate predictive performance over time. Results: Thirty-day mortality was significantly associated with a higher Japan SCORE; survivors had significantly lower scores than non-survivors (5.5% vs. 25.8%, p < 0.05). One-year mortality was significantly associated with nutritional status, as survivors showed a significantly higher GNRI than non-survivors (92.0 vs. 86.0, p < 0.05). Time-dependent ROC analysis revealed that the GNRI and SPINACH SCORE’s sustained prognostic accuracy beyond 1 year. Calibration plots showed good agreement between predicted and observed probabilities for the SPINACH SCORE and GNRI, while decision curve analysis (DCA) demonstrated that these two models provided greater net clinical benefit across a range of thresholds, particularly in the 5–20% range. Conclusions: Japan SCORE is effective for short-term risk prediction, while SPINACH SCORE and GNRI offer superior prognostic value for mid-term outcomes. These scoring systems may support preoperative risk stratification and decision-making in CLTI patients undergoing cardiac surgery.

Interchain disulfide bonds in monoclonal antibodies may be reduced during large-scale mAb production using Chinese hamster ovary (CHO) cells. This reaction lowers the mAb product yield and purity; however, it may be prevented by screening cell lines that are unsusceptible to reduction and using them in mAb production. Antibody reduction susceptibility may be cell line-dependent. To the best of our knowledge, however, an efficient method of screening reduction-unsusceptible CHO cell lines has not been previously reported. Here, we report a novel screening method that can simultaneously detect and identify mAb reduction susceptibility in lysates containing ≤ 48 CHO cell lines. This evaluation system was equally effective and generated similar results at all culture scales, including 250 mL, 3 L, and 1000 L. Furthermore, we discovered that reduction-susceptible cell lines contained higher total intracellular nicotinamide adenine dinucleotide phosphate (NADPH) and NADP + concentrations than reduction-unsusceptible cell lines, regardless of whether they expressed immunoglobulin (Ig)G4 or IgG1. NADPH or NADP + supplementation in the lysate of reduction-unsusceptible cells resulted in mAb reduction. Application of the innovative CHO cell line screening approach could mitigate or prevent reductions in large-scale mAb generation from CHO cells.

The Hokkaido Eastern Iburi Earthquake (M = 6.7) occurred on Sep. 6, 2018 in the southern part of Central Hokkaido, Japan. Since Paleogene, this region has experienced the dextral oblique transpression between the Eurasia and North American (Okhotsk) Plates and the subsequent collision between the Northeast Japan Arc and the Kuril Arc due to the oblique subduction of the Pacific Plate. This earthquake occurred beneath the foreland fold-and-thrust belt of the Hidaka Collision zone developed by the collision process, and is characterized by its deep focal depth (~ 37 km) and complicated rupture process. The reanalyses of controlled source seismic data collected in the 1998–2000 Hokkaido Transect Project revealed the detailed structure beneath the fold-and-thrust belt, and its relationship with the aftershock activity of this earthquake. Our reflection processing using the CRS/MDRS stacking method imaged for the first time the lower crust and uppermost mantle structures of the Northeast Japan Arc underthrust beneath a thick (~ 5–10 km) sedimentary package of the fold-and-thrust belt. Based on the analysis of the refraction/wide-angle reflection data, the total thickness of this Northeast Japan Arc crust is only 16–22 km. The Moho is at depths of 26–28 km in the source region of the Hokkaido Eastern Iburi Earthquake. Our hypocenter determination using a 3D structure model shows that most of the aftershocks are distributed in a depth range of 7–45 km with steep geometry facing to the east. The seismic activity is quite low within the thick sediments of the fold–thrust belt, from which we find no indication on the relationship of this event with the shallow (< 10–15 km) and rather flat active faults developed in the fold-and-thrust belt. On the other hand, a number of aftershocks are distributed below the Moho. This high activity may be caused by the cold crust delaminated from the Kuril Arc side by the arc–arc collision, which prevents the thermal circulation and cools the forearc uppermost mantle to generate an environment more favorable for brittle fracture.

Background Malignant lymphoma rarely mimics an infected arterial aneurysm and a ruptured arterial aneurysm because of similar imaging findings, leading to misdiagnosis. The hematomas of ruptured aneurysms are radiologically difficult to distinguish from those of malignant lymphoma in emergency settings. Hence, a definitive diagnosis is crucial to avoid unnecessary surgery. Case presentation A man in his 80s with hematuria and shock vital had right internal iliac artery aneurysm (IIAA) and perianeurysmal fluid retention, which appeared to be a ruptured or an infected aneurysm. Treatment was initiated for infected IIAA instead of for ruptured IIAA. Systemic inflammatory response syndrome developed, and the infectious sources were assessed. Pacemaker lead and urinary tract infections were identified and treated; however, blood pressure was unstable. The aneurysm was treated with endovascular aortic aneurysm repair following antibiotic therapy; however, fluid retention increased, and inflammatory status and hematuria deteriorated. Open surgical conversion was performed to manage the infected lesions. Although an iliopsoas abscess was detected during surgery and nephrectomy and ureterectomy were performed to control the hematuria, analysis of the removed tissues led to the pathological diagnosis of diffuse large B-cell lymphoma (DLBCL). Conclusions We encountered a case of DLBCL with imaging findings mimicking an infected internal iliac artery aneurysm, and definitive diagnosis was made more than 2 months after the initial examination. Definitively diagnosing malignant lymphoma around an iliac artery aneurysm based merely on symptoms and imaging findings is extremely difficult. Thus, histological examination should be actively performed in atypical infected aneurysms.