Achievements of PVS (Primo Vascular System) Research from a Historical Perspective.

The purpose of this paper is to compare the biological research carried out in North Korea with the modern outcomes in the same field, from a historical perspective. In the 1960s, the group led by Bong-Han Kim asserted the existence of a fundamental circulatory system in the human body. Their findings were introduced in five papers as well as in the newspaper Rodong Sinmun. The size of the group, the range of equipment, and their findings expanded gradually, and the final paper on blood cells would be only published one of over sixty papers reported at that time. In the five papers, some unclear and inconsistent contents were found. Meanwhile, in the 2000s, PVS (primo vascular system) researchers have published over one hundred papers to prove the existence of this novel system. Some trends have emerged in approximately sixty papers as follows: The research on the identification of the anatomical and histological characteristics has gradually expanded to encompass the system's own functioning. Also, new visual results (e.g. before and after dyeing, and its comparison with blood clots) and the exploration of possible medical applications (e.g. cancer metastasis channels or stem cells location) have been proposed. However, it is difficult to identify papers which comprehensively represented the elements claimed by Bong-Han Kim's group. In addition, papers have been published more in alternative or Oriental medicine journals than in Western biomedical journals. It seems necessary to report more existence of the system in one laboratory animal and in more influential journals.

Hypo-trimethylation of Histone H3 Lysine 4 and Hyper-tri/dimethylation of Histone H3 Lysine 27 as Epigenetic Markers of Poor Prognosis in Patients with Primary Central Nervous System Lymphoma.

PURPOSE: This study aimed to investigate the methylation status of major histone modification sites in primary central nervous system lymphoma (PCNSL) samples and examine their prognostic roles in patients with PCNSL. MATERIALS AND METHODS: Between 2007 and 2020, 87 patients were histopathologically diagnosed with PCNSL. We performed immunohistochemical staining of the formalin-fixed paraffin-embedded samples of PCNSL for major histone modification sites, such as H3K4, H3K9, H3K27, H3K14, and H3K36. After detection of meaningful methylation sites, we examined histone modification enzymes that induce methylation or demethylation at each site using immunohistochemical staining. The meaningful immunoreactivity was validated by western blotting using fresh tissue of PCNSL. RESULTS: More frequent recurrences were found in hypomethylation of H3K4me3 (p=0.004) and hypermethylation of H3K27me2 (p<0.001) and H3K27me3 (p=0.002). These factors were also statistically related to short PFS and overall survival in the univariate and multivariate analyses. Next, histone modification enzymes inducing the demethylation of H3K4 (lysine-specific demethylase-1/2 and Jumonji AT-rich interactive domain [JARID] 1A-D]) and methylation of H3K27 (enhancer of zeste homolog [EZH]-1/2) were immu- nohistochemically stained. Among them, the immunoreactivity of JARID1A inversely associated with the methylation status of H3K4me3 (R2=-1.431), and immunoreactivity of EZH2 was directly associated with the methylation status of H3K27me2 (R2=0.667) and H3K27me3 (R2=0.604). These results were validated by western blotting in fresh PCNSL samples. CONCLUSION: Our study suggests that hypomethylation of H3K4me3 and hypermethylation of H3K27me2 and H3K27me3 could be associated with poor outcomes in patients with PCNSL and that these relationships are modified by JARID1A and EZH2.

Association of Aortic Arch Calcification on Chest X-ray with Procedural Thromboembolism after Mechanical Thrombectomy for Acute Ischemic Stroke.

Background and Objective: Procedural thromboembolism after a mechanical thrombectomy (MT) for an acute ischemic stroke (AIS) has rarely been studied. It may occur from the artery-to-artery embolization of atherosclerotic plaque in the aortic arch. We investigated the relationship between aortic arch calcification (AoAC) on a chest X-ray and procedural thromboembolism on diffusion-weighted imaging (DWI) after an MT. Materials and Methods: From January 2017 to December 2020, 131 patients underwent DWI within two days following an MT for an AIS. Procedural thromboembolism was defined as new DWI-positive lesions in other territories from the occluded artery on DWI within two days after MT. Results: Procedural thromboembolism was observed in 30 (22.9%) patients. Procedural thromboembolism was associated with old age (72.3 ± 9.44 vs. 65.7 ± 12.8 years, p = 0.003), a longer procedural time (77.6 ± 37.6 vs. 60.1 ± 29.7 min, p = 0.024), and AoAC (calcification (73.3%) vs. no calcification (29.7%), p < 0.001). Multivariable logistic regression analysis showed that procedural thromboembolism was independently associated with AoAC (adjusted odds ratio (OR): 6.107, adjusted 95% confidence interval (CI): 2.374-15.705, p < 0.001) and a longer procedural time (adjusted OR: 1.015, adjusted 95% CI: 1.001-1.030, p = 0.031). Conclusions: Procedural thromboembolism after an MT for an AIS was related to AoAC on a chest X-ray and a longer procedural time. Our results suggest that although rapid recanalization is the most crucial goal of an MT for an AIS, the importance of the careful advance of the guiding catheter through the aortic arch should not be underestimated to reduce the risk of procedural thromboembolism, especially in patients with AoAC on a chest X-ray.

Ensuring reproducibility and ethics in animal experiments reporting in Korea using the ARRIVE guideline.

The aim of this study is to evaluate the reporting quality of animal experiments in Korea using the Animals in Research: Reporting In Vivo Experiments (ARRIVE) guideline developed in 2010 to overcome the reproducibility problem and to encourage compliance with replacement, refinement and reduction of animals in research (3R's principle). We reviewed 50 papers published by a Korean research group from 2013 to 2016 and scored the conformity with the 20-items ARRIVE guideline. The median conformity score was 39.50%. For more precise evaluation, the 20 items were subdivided into 57 sub-items. Among the sub-items, status of experimental animals, housing and husbandry were described under the average level. Microenvironment sub-items, such as enrichment, bedding material, cage type, number of companions, scored under 10%. Although statistical methods used for the studies were given in most publications (84%), sample size calculation and statistical assumption were rarely described. Most publications mentioned the IACUC approval, but only 8% mentioned welfare-related assessments and interventions, and only 4% mentioned any implications of experimental methods or findings for 3R. We may recommend the revision of the present IACUC proposal to collect more detailed information and improving educational program for animal researchers according to the ARRIVE guideline.

Essential Experimental Methods for Identifying Bonghan Systems as a Basis for Korean Medicine: Focusing on Visual Materials from Original Papers and Modern Outcomes.

In the 1960s, through studies on Korean Medicine, Bonghan Kim proposed the Bonghan systems (BS) as the anatomical reality of the acupuncture meridians based on various experimental data. Since 2002, several groups, mainly led by a team at Seoul National University, who renamed the BS as the primo vascular system (PVS), have published around 70 papers showing biological structures corresponding to the BS. However, it is still difficult for other researchers to find them, especially under the skin, which Bonghan Kim first reported as acupuncture points, due to similar-looking biological tissues, for example, the lymphatic vessels, and such artifacts as blood clots or fascia debris. To solve these drawbacks, we examined the main methods for identifying the BS by comparing the original papers with the modern outcomes in terms of the common physical/chemical characteristics of the BS. In addition, effective methods of staining and microscopic observations discovered by modern teams are synthetically explained using visual materials such as diagrams and photos. Through the essentially organized methods in this review paper, we suggest that one can find the BS under the skin as putative acupuncture points by tracing the intraexternal BS, from which a new Korean Medicine will be born.

Evidence for novel age-dependent network structures as a putative primo vascular network in the dura mater of the rat brain.

With chromium-hematoxylin staining, we found evidence for the existence of novel age-dependent network structures in the dura mater of rat brains. Under stereomicroscopy, we noticed that chromium-hematoxylin-stained threadlike structures, which were barely observable in 1-week-old rats, were networked in specific areas of the brain, for example, the lateral lobes and the cerebella, in 4-week-old rats. In 7-week-old rats, those structures were found to have become larger and better networked. With phase contrast microscopy, we found that in 1-week-old rats, chromium-hematoxylin-stained granules were scattered in the same areas of the brain in which the network structures would later be observed in the 4- and 7-week-old rats. Such age-dependent network structures were examined by using optical and transmission electron microscopy, and the following results were obtained. The scattered granules fused into networks with increasing age. Cross-sections of the age-dependent network structures demonstrated heavily-stained basophilic substructures. Transmission electron microscopy revealed the basophilic substructures to be clusters with high electron densities consisting of nanosized particles. We report these data as evidence for the existence of age-dependent network structures in the dura mater, we discuss their putative functions of age-dependent network structures beyond the general concept of the dura mater as a supporting matrix.

Formative research on the primo vascular system and acceptance by the korean scientific community: the gap between creative basic science and practical convergence technology.

The purpose of this study was to trace the formative process of primo vascular system (PVS) research over the past decade and to describe the characteristics of the Korean scientific community. By publishing approximately 30 papers in journals ranking in the Science Citation Index (Expanded), the PVS research team actively convinced domestic and international scientists of the anatomical existence of the PVS and its possible application to Korean and Western medicine. In addition, by sharing the PVS observation technique, the team promoted the dissemination and further pursuit of the research. In 2012, however, PVS researchers performed smaller scale research without advancing to a higher level as compared to the early days. The main reasons were found to be the Korean Research and Development policy of supporting creative, small-scale basic research and applied research of Western scientific fields that promised potentially greater success on an extensive scale; the indifference concerning, and the disbelief in, the existence of a new circulatory system were shown by the Western medical community. In addition, the Oriental medical community was apathetic about working with the PVS team. Professors Kwang-Sup Soh and Byung-Cheon Lee were the prime movers of PVS research under difficult conditions. Spurred by their belief in the existence and significance of the PVS, they continued with their research despite insufficient experimental data. The Korean scientific community is not ready to promote the Korea-oriented creative field of the PVS team.