Exploring the impact of N4-acetylcytidine modification in RNA on non-neoplastic disease: unveiling its role in pathogenesis and therapeutic opportunities.

RNA modifications include not only methylation modifications, such as m6A, but also acetylation modifications, which constitute a complex interaction involving "writers," "readers," and "erasers" that play crucial roles in growth, genetics, and disease. N4-acetylcytidine (ac4C) is an ancient and highly conserved RNA modification that plays a profound role in the pathogenesis of a wide range of diseases. This review provides insights into the functional impact of ac4C modifications in disease and introduces new perspectives for disease treatment. These studies provide important insights into the biological functions of post-transcriptional RNA modifications and their potential roles in disease mechanisms, offering new perspectives and strategies for disease treatment.

A Retrospective Study Comparing Pharmacomechanical Thrombectomy with Catheter-Directed Thrombolysis for Acute Deep Venous Thrombosis.

BACKGROUND: This study aims to conduct a comparative analysis of the clinical efficacy and safety between pharmacomechanical thrombectomy (PMT) and catheter-directed thrombolysis (CDT) in the context of acute lower-extremity deep venous thrombosis (LEDVT). METHODS: A retrospective review of our institution's patient database spanning from February 2011 to December 2019 was performed to identify cases of acute LEDVT. The patients were categorized into 2 distinct groups based on the thrombolytic interventions administered: the PMT group, specifically denoting PMT with AngioJet in our investigation, and the CDT group. Comprehensive data sets encompassing patient demographics, risk factors, procedural specifics, thrombolysis grading, and complications were collected. Subsequent follow-up evaluations at the 2-year mark posttreatment included assessments of postthrombotic syndrome (PTS) and the quality of life. RESULTS: Among the 348 patients identified (mean age: 50.12 ± 15.87 years; 194 females), 200 underwent CDT during the early stage (2011 to 2017), while 148 received PMT between 2017 and 2019. Baseline data between the 2 groups exhibited no statistically significant differences. Thrombus scores significantly decreased in both cohorts posttherapy (each P < 0.001).Patients subjected to PMT demonstrated higher thrombolysis rates (77.35 ± 9.44% vs. 50.85 ± 6.72%), reduced administration of the thrombolytic agent urokinase [20 (20€20) vs. 350 (263€416), P < 0.001], larger limb circumference differences (above the knee: 6.03 ± 1.76 cm vs. 4.51 ± 1.82 cm, P < 0.001; below the knee: 2.90 ± 1.16 cm vs. 2.51 ± 0.90 cm, P < 0.001), and shorter lengths of stay (7.19 ± 3.11 days vs. 12.33 ± 4.77 days, P < 0.001). However, the PMT group exhibited a higher decline in hemoglobin levels (13.41 ± 10.59 g/L vs. 10.88 ± 11.41 g/L, P = 0.038) and an increase in creatinine levels [9.58 (2.32€15.82) umol/L vs. 4.53 (2.87€6.08) umol/L, P < 0.001] compared to the CDT group. No statistically significant differences were observed in the numbers of balloon angioplasty, stent implantation (each P > 0.050), and minor and major complications between the 2 groups. At the 1-year follow-up, PTS occurred in 13.51% of the PMT group compared to 26% of the CDT group (P = 0.025), with a higher incidence of moderate-severe PTS in the CDT group (8% vs. 2.7%, P = 0.036). At the 2-year follow-up, PTS was observed in 16.2% of the PMT group and 31.5% in the CDT group, P = 0.004. Preoperative and postoperative D-values of 36-Item Short Form Health Survey (SF-36) Physical Component Summary and SF-36 Mental Component Summary showed no statistically significant between-group differences. CONCLUSIONS: In our institutional experience, both PMT and CDT have proven to be effective and safe therapeutic approaches for managing acute LEDVT. PMT, in particular, demonstrated superior efficacy in achieving thrombosis resolution and mitigating the risk of PTS, affirming its role as a favorable intervention in this clinical context.

The external jugular vein is a feasible and safe alternative access for retrieval of inferior vena cava filter.

PURPOSE: The purpose is to analyze whether the external jugular vein (EJV) is a feasible and safe alternative access for the retrieval IVCFs designed for the jugular approach. METHODS: This study was designed as a nonrandomized, controlled study. The patients were divided into two groups: the IJV or EJV access groups. All operations were performed by the vascular surgery team. The main outcome was the technical success rate. The secondary outcomes included (1) the IVCF retrieval rate; (2) the time required to puncture the access vein (min); (3) the number of punctures required for access, and other aspects. RESULTS: A total of 119 patients were recruited for IVCF retrieval. Seventeen patients refused to join this trial, leaving 58 patients in the IJV group and 44 patients in the EJV group. In the IJV group, technical success was not achieved in one patient who started in the EJV group and was transferred to the IJV group. There was no significant difference in age, comorbidities, or technical success rate between the two groups. Significant differences were observed in puncture time (min), number of punctures, and inadvertent puncture of the carotid artery. All of the patients were discharged 1 or 2 days after the operation. CONCLUSION: EJV is safe and feasible alternative access for the retrieval of IVCFs that are designed for jugular approaches.

The Roles of FHL3 in Cancer.

The four and a half LIM domain protein 3, also named the LIM-protein FHL3, belongs to the LIM-only family. Based on the special structure of LIM-only proteins, FHL3 can perform significant functions in muscle proliferation and cardiovascular diseases by regulating cell growth and signal transduction. In recent years, there has been increasing evidence of a relation between FHLs and tumor biology, since FHL3 is often overexpressed or downregulated in different cancers. On the one hand, FHL3 can function as a tumor suppressor and influence the expression of downstream genes. On the other hand, FHL3 can also play a role as an oncoprotein in some cancers to promote tumor progression via phosphorylation. Thus, FHL3 is proposed to have a dual effect on cancer progression, reflecting its complex roles in cancer. This review focuses on the roles of FHL3 in cancer progression and discusses the interaction of FHL3 with other proteins and transcription factors. Finally, the clinical significance of FHL3 for the treatment of cancers is discussed.

Endovascular removal of a misplaced ureteral stent in the vena cava: a complication of ultrasound-guided percutaneous nephrolithotomy.

Intravascular migration of a double J stent into the inferior vena cava is an uncommon complication. Active prevention, timely diagnosis, and early intervention are crucial for this complication. Intravascular interventional therapy is relatively easy, less traumatic, and has a high success rate. It can be used to select patients for intravascular ectopic DJS treatment.

Treatment of Extracranial Carotid Artery Aneurysm: Fifteen Years' Experience at a Single Institution.

BACKGROUND: The purpose of this study is to record our institution's experience in the management of extracranial carotid artery aneurysms (ECCAs) over the past 15 years. METHODS: A retrospective chart review was performed on consecutive patients with ECCAs from April 2003 to December 2017. Outpatient and inpatient clinic charts were reviewed. All the patients were treated by open surgery between 2003 and 2008. For other patients, the treatment methods included open surgery, endovascular surgery, and hybrid operations which were dependent on the aneurysm anatomy, as well as conservative management. In open series, a carotid shunt was applied and transcranial color Doppler was selectively used for intraoperative monitoring of cerebral blood flow. The resected aneurysm sacs were tested with hematoxylin and eosin stains. Each case was reexamined one month after the patients were discharged from the hospital. A questionnaire survey, a clinical examination, and duplex ultrasonography or computed tomography angiography imaging were carried out. The patients were then reexamined three and six months after surgery and then annually. RESULTS: Thirty ECCAs were treated in 30 patients-14 men and 16 women, with a mean age of 54 ± 13 years. Four types of carotid aneurysms were identified: type I, II, III, and V, with 17, 3, 1, and 9 patients, respectively. From 2003 to 2008, there were eight patients (type I: seven; type II: one), and all were treated by open surgery and one suffered transient cranial nerve palsy. From 2009 to 2017, two patients were treated with conservative management, ten were treated with open surgery, nine were treated with endovascular surgery, and one was treated with hybrid operation. Among the patients who were treated with open surgery, two suffered neck hematoma. All patients recovered well without complications in the endovascular surgery group. Twenty-seven patients presented for follow-up and without contralateral aneurysms or other complications. CONCLUSIONS: The optimal treatment of ECCAs is dependent on the morphology of the carotid artery and properties of aneurysms. Open surgical repair is a suitable and safe procedure for type I ECCAs when the aneurysms are concomitant with kinking in the internal carotid artery. Endovascular treatment is an effective alternative to open surgery for false ECCA repair.

The Treatment of Infected Femoral Artery Pseudoaneurysms Secondary to Drug Abuse: 11 Years of Experience at a Single Institution.

BACKGROUND: The purpose of our study is to analyze the methods of treating infected femoral artery pseudoaneurysms (IFAPs), and also to identify the most appropriate method, especially for patients with a long history of drug abuse. METHODS: A retrospective chart review of 88 consecutive IFAPs secondary to drug abuse between 2003 and 2014 was performed. Outpatient clinic charts were reviewed, as well as inpatient and anesthesia records. All patients had undergone a computer tomography angiography or contrast computer tomography to confirm their diagnosis. Routine blood tests were performed. The treatment methods included common femoral artery ligation (CFA) along with local debridement and drainage, direct oversewing, and amputation. A clamping test of the distal external iliac artery (EIA) or the common femoral artery was performed after vessel isolation, during which the oxygen saturation of the blood at the end of the affected limb was examined with a continuous pulse oximeter. Skin samples from affected limbs were tested with hematoxylin and eosin (HE) stain. RESULTS: There were a total of 88 patients, of which 79 and 9 came from emergency and outpatient, respectively. Acute hemorrhage at the injection site, pulsatile mass, septic syndrome, and necrosis were present in 65, 14, 8, and 1 patients, respectively. All patients experienced groin pain. Thigh or leg swelling was present in 63 patients. The drug injection history was a mean 6.9 ± 4.1 years. Seventy-four patients presented with anemia and 75 patients presented with hypoproteinemia. Hepatitis B, hepatitis C, syphilis, and HIV were found in 42, 57, 12, and 2 patients, respectively. One patient gave up the treatment. One patient was treated by amputation along with CFA ligation and local debridement because the limb was necrotic on admission. Three patients with short drug injection abuse history and local slight infection were treated by direct oversewing. Eighty-three patients, of which 27 had a drug injection history shorter than 5 years and 56 patients longer than 5 years, were treated by CFA ligation and local debridement. All patients' oxygen saturation of the affected limbs was higher than 90% after distal EIA clamping test and ligation, except the amputation patient. None of these required amputation. One patient, whose injection history was only half a year, underwent an operation for acute ischemic performance. Forty patients had differing degrees of lymph extravasations and were treated by injecting 70% methylated amine diatrizoate. HE stain showed that there were an abundant of microcirculation vessels in IFAP patients. The mean follow-up period was mean (26 ± 14) months from 3 months to 61 months. In the group with a history shorter than 5 years, 10 patients had mild claudication in the first 3 months and then relieved from 6 months. However, in patients with a history longer than 5 years, no case presented claudication. Many of them admitted to drug abuse after surgery and rehabilitation. CONCLUSIONS: The appropriate and tolerated treatment for most IFAP is arterial ligation, particularly in patients with an injected drug history longer than 5 years. Primary repair may be adopted for special IFAP patients with short drug injection history and limit infection to avoid severe ischemia complication. Medical staff should take strict precautions and protection measures.

Inhibition of development of experimental abdominal aortic aneurysm by c-jun N-terminal protein kinase inhibitor combined with lysyl oxidase gene modified smooth muscle progenitor cells.

Chronic inflammation, imbalance between the extracellular matrix synthesis and degradation, and loss of vascular smooth muscle cells (SMCs) contribute to the development of abdominal aortic aneurysm (AAA). The purpose of this study was to investigate the effect of the therapy with periaortic incubation of c-Jun N-terminal protein kinase inhibitor SP600125 infused from an osmotic pump and subadventitial injection of lysyl oxidase (LOX) gene modified autologous smooth muscle progenitor cells (SPCs) on treatment of AAA in a rabbit model. Obvious dilation of the abdominal aorta in the control group was caused by periaortic incubation of calcium chloride and elastase. But the progression of aortic dilation was significantly decreased after the treatment with SP600125 and LOX gene modified SPCs compared to the treatment with phosphate-buffered saline. This therapy could inhibit matrix metalloproteinases expression, enhance elastin synthesis, improve preservation of elastic laminar integrity, benefit SPCs survival and restore SMCs population. It seemed that this method might provide a novel therapeutic strategy to treat AAA.

Activating mutation (V617F) in the tyrosine kinase JAK2 is absent in locally-confined or castration-resistant prostate cancer.

BACKGROUND: Transcription factor Stat5a/b is highly critical for the viability of human prostate cancer cells in vitro and for prostate tumor growth in vivo. Stat5 is constitutively active in clinical prostate cancers but not in the normal human prostate epithelium. Moreover, Stat5a/b activation in prostate cancer is associated with high histological grade of prostate cancer. However, the molecular mechanisms underlying constitutive activation of Stat5a/b in prostate cancer are unclear. The receptor-associated tyrosine kinase Jak2 is a known key activator of Stat5a/b in prostate cancer cells in response to ligand stimulation. Recently, a single gain-of-function point mutation of JAK2 was described in myeloproliferative diseases leading to constitutive Jak2 kinase activity, subsequent Stat5a/b activation and involvement of V617F Jak2 in the pathogenesis of myeloproliferative disorders. MATERIALS AND METHODS: We determined whether JAK2 undergoes the V617F activating mutation during clinical progression of human prostate cancer using a highly sensitive assay (amplification refractory mutation system) and a unique material of fresh specimens from organ-confined or castration-resistant prostate cancers. RESULTS: The JAK2 V617F mutation was not found in any of the normal or malignant prostate samples analyzed in this study. CONCLUSIONS: Future work should focus on determining the molecular mechanisms other than V617F mutation of Jak2 resulting in continuous Stat5 activation in clinical prostate cancers.