50 Years of Bong-Han Theory and 10 Years of Primo Vascular System

The primo vascular system (PVS) was first introduced by Bong-Han Kim via his five research reports. Among these the third report was most extensive and conclusive in terms of the PVS anatomy and physiology relating to the acupuncture meridians. His study results, unfortunately, were not reproduced by other scientists because he did not describe the materials and methods in detail. In 2002, a research team in Seoul National University reinitiated the PVS research, confirmed the existence of PVS in various organs, and discovered new characteristics of PVS. Two important examples are as follows: PVS was found in the adipose tissue and around cancer tissues. In parallel to these new findings, new methods for observing and identifying PVS were developed. Studies on the cell and material content inside the PVS, including the immune function cells and stem cells, are being progressed. In this review, Bong-Han Kim’s study results in his third report are summarized, and the new results after him are briefly reviewed. In the last section, the obstacles in finding the PVS in the skin as an anatomical structure of acupuncture meridian are discussed

Association of serum adipocytokine levels with cardiac autonomic neuropathy in type 2 diabetic patients

<p>Abstract</p> <p>Background</p> <p>Cardiac autonomic neuropathy (CAN) is a common complication of diabetes associated with poor prognosis. In addition, the autonomic imbalance is associated with cardiovascular disease (CVD) in diabetes. It is thought that adipocytokines contribute to the increased risk of vascular complications in patients with type 2 diabetes mellitus (T2DM). However, literature data on the association between CAN with adipocytokines such as leptin, tumor necrosis factor-alpha (TNF-alpha), adiponectin in subjects with T2DM is limited.</p> <p>Therefore, in the present study, we examined the relationship between fasting serum leptin, TNF- alpha and adiponectin and CAN in Korean T2DM patients.</p> <p>Methods</p> <p>A total of 142 T2DM patients (94 males, 48 females) were recruited. CAN was assessed by the five tests according to the Ewing's protocol and the time and frequency domain of the heart rate variability (HRV) was evaluated. Serum TNF-alpha and adiponectin levels were measured using enzyme-linked immunosorbent assay and serum leptin levels were measured using radioimmunoassay.</p> <p>Results</p> <p>Although, the mean levels of leptin, TNF-alpha and adiponectin were not significantly different between the groups with and without CAN, the levels of leptin and adiponectin had a tendency to increase as the score of CAN increased (p = 0.05, p = 0.036). Serum leptin levels demonstrated a negative correlation with low frequency (LF) in the upright position (p = 0.037). Regarding TNF-alpha, a significant negative correlation was observed with SDNN and RMSSD in the upright position (p = 0.023, p = 0.019). Adiponectin levels were not related to any HRV parameters. Multivariate logistic regression analysis demonstrated that the odds of CAN increased with a longer duration of diabetes (1.25, [1.07-1.47]) and higher homeostatic model of assessment-insulin resistance (HOMA-IR) (5.47, [1.8-16.5]). The relative risks for the presence of CAN were 14.1 and 51.6 for the adiponectin 2^nd, 3^rdtertiles when compared with first tertile (p-value for trend = 0.022).</p> <p>Conclusions</p> <p>In the present study, the higher serum adiponectin levels and HOMA-IR were associated with an increased risk for the presence of CAN. Also, the CAN score correlated with the serum adiponectin. Serum adipocytokines such as leptin and TNF-alpha were significantly correlated with parameters of HRV, representative markers of CAN. Future prospective studies with larger number of patients are required to establish a direct relationship between plasma adipocytokine concentrations and the development or severity of CAN.</p

Educational Inequalities in Self-Rated Health in Europe and South Korea

While numerous comparative works on the magnitude of health inequalities in Europe have been conducted, there is a paucity of research that encompasses non-European nations such as Asian countries. This study was conducted to compare Europe and Korea in terms of educational health inequalities, with poor self-rated health (SRH) as the outcome variable. The European Union Statistics on Income and Living Conditions and the Korea National Health and Nutrition Examination Survey in 2017 were used (31 countries). Adult men and women aged 20+ years were included (207,245 men and 238,007 women). The age-standardized, sex-specific prevalence of poor SRH by educational level was computed. The slope index of inequality (SII) and relative index of inequality (RII) were calculated. The prevalence of poor SRH was higher in Korea than in other countries for both low/middle- and highly educated individuals. Among highly educated Koreans, the proportion of less healthy women was higher than that of less healthy men. Korea’s SII was the highest for men (15.7%) and the ninth-highest for women (10.4%). In contrast, Korea’s RII was the third-lowest for men (3.27), and the lowest among women (1.98). This high-SII–low-RII mix seems to have been generated by the high level of baseline poor SRH

Trends in life expectancy among medical aid beneficiaries and National Health Insurance beneficiaries in Korea between 2004 and 2017

Background Medical Aid beneficiaries in Korea are more likely to have poor health status and to receive insufficient healthcare services, but their life expectancy has not been compared with that of National Health Insurance beneficiaries. Methods We used the National Health Information Database in Korea to obtain aggregate data on the numbers of population and deaths according to calendar year (2004 to 2017), sex, age group, and insurance eligibility (Medical Aid or National Health Insurance). Between 2004 and 2017, a summed total of 697,503,634 subjects (combining numbers of subjects for 14 years) and 3,536,778 deaths, including 22,417,216 Medical Aid beneficiaries and 499,604 associated deaths, were used to construct annual abridged life tables. Results In 2017, the life expectancy of Medical Aid beneficiaries was 70.9 years, while that of National Health Insurance beneficiaries was 83.7 years. Between 2004 and 2017, life expectancy for Medical Aid beneficiaries increased by 8.7 years in men and 6.1 years in women, while life expectancy for National Health Insurance beneficiaries increased by 5.2 years in men and 4.5 years in women. The life expectancy difference between National Health Insurance beneficiaries and Medical Aid beneficiaries was especially great among men across all study periods. The life expectancy difference was 15.8 years for men and 8.9 years for women in 2017. Conclusions The life expectancy of Medical Aid beneficiaries was shorter than that of National Health Insurance beneficiaries. The government should implement policies to deliver more adequate health care to Medical Aid beneficiaries.This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI18C0446). The funding body did not have any role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript

Differential associations of central and brachial blood pressure with carotid atherosclerosis and microvascular complications in patients with type 2 diabetes

BACKGROUND: We examined the relationship between central blood pressure (BP), brachial BP with carotid atherosclerosis and microvascular complications in type 2 diabetes mellitus (T2DM). METHODS: We recruited 201 patients who were evaluated for central BP, brachial BP, carotid ultrasonography, brachial-ankle pulse wave velocity (baPWV), ankle-brachial index (ABI) and microvascular complications. Central BP were calculated using a radial automated tonometric system. RESULTS: Agreement between central BP and brachial BP was very strong (concordance correlation coefficient between central and brachial SBP = 0.889, between central and brachial PP = 0.816). Central pulse pressure (PP) was correlated with mean carotid intima-media thickness (CIMT), baPWV and ABI, whereas brachial PP was borderline significantly correlated with CIMT. The prevalence of nephropathy(DN) and retinopathy(DR) according to the brachial PP tertiles increased, the prevalences of microvascular complications were not different across central PP tertiles. In multivariate analysis, the relative risks (RRs) for the presence of DR were 1.2 and 4.6 for the brachial PP tertiles 2 and 3 when compared with the first tertile. Also, the RRs for the presence of DN were 1.02 and 3 for the brachial PP tertiles 2 and 3 when compared with the first tertile. CONCLUSIONS: Agreement of central BP and brachial BP was very strong. Nonetheless, this study showed that higher brachial PP levels are associated with increased probability for the presence of microvascular complications such as DR/DN. However, there are no associations with central SBP and central PP with microvascular complications. Central BP levels than brachial BP are correlated with surrogate marker of macrovascular complications

Effect of rhBMP-2 applied with a 3D-printed titanium implant on new bone formation in rabbit calvarium

Objective: This study sought to compare the biocompatibility of a three-dimensional (3D)-printed titanium implant with a conventional machined titanium product, as well as the effect of such implant applied with recombinant human Bone Morphogenetic Protein Type 2 (rhBMP-2) for guided bone regeneration.&nbsp;Methodology: Disk-shaped titanium specimens fabricated either by the conventional machining technique or by the 3D-printing technique were compared by MC3T3-E1 cells cytotoxicity assay. New bone formation was evaluated using a rapid prototype titanium cap applied to the calvaria of 10 rabbits, which were divided into two groups: one including an atelopeptide collagen plug on one side of the cap (group I) and the other including a plug with rhBMP-2 on the other side (group II). At six and 12 weeks after euthanasia, rabbits calvaria underwent morphometric analysis through radiological and histological examination.&nbsp;Results: Through the cytotoxicity assay, we identified a significantly higher number of MC3T3-E1 cells in the 3D-printed specimen when compared to the machined specimen after 48 hours of culture. Moreover, morphometric analysis indicated significantly greater bone formation at week 12 on the side where rhBMP-2 was applied when evaluating the upper portion immediately below the ca p. Conclusion: The results suggest that 3D-printed titanium implant applied with rhBMP-2 enables new bone formation

Comparison of three small-area mortality metrics according to urbanity in Korea: the standardized mortality ratio, comparative mortality figure, and life expectancy

Abstract Background This study aimed to compare three small-area level mortality metrics according to urbanity in Korea: the standardized mortality ratio (SMR), comparative mortality figure (CMF), and life expectancy (LE) by urbanity. Methods We utilized the National Health Information Database to obtain annual small-area level age-specific numbers of population and deaths in Korea between 2013 and 2017. First, differences in the SMR by urbanity were examined, assuming the same age-specific mortality rates in all small areas. Second, we explored the differences in ranking obtained using the three metrics (SMR, CMF, and LE). Third, the ratio of CMF to SMR by population was analyzed according to urbanity. Results We found that the age-specific population distributions in urbanized areas were similar, but rural areas had a relatively old population structure. The age-specific mortality ratio also differed by urbanity. Assuming the same rate of age-specific mortality across all small areas, we found that comparable median values in all areas. However, areas with a high SMR showed a strong predominance of metropolitan areas. The ranking by SMR differed markedly from the rankings by CMF and LE, especially in areas of high mortality, while the latter two metrics did not differ notably. The ratio of CMF to SMR showed larger variations in small areas in rural areas, particularly in those with small populations, than in metropolitan and urban areas. Conclusions In a comparison of multiple SMRs, bias could exist if the study areas have large differences in population structure. The use of CMF or LE should be considered for comparisons if it is possible to acquire age-specific mortality data for each small area

Unleashing the full potential of Hsp90 inhibitors as cancer therapeutics through simultaneous inactivation of Hsp90, Grp94, and TRAP1

Cancer therapeutics: Extending a drug&apos;s reach A new drug that blocks heat shock proteins (HSPs), helper proteins that are co-opted by cancer cells to promote tumor growth, shows promise for cancer treatment. Several drugs have targeted HSPs, since cancer cells are known to hijack these helper proteins to shield themselves from destruction by the body. However, the drugs have had limited success. Hye-Kyung Park and Byoung Heon Kang at Ulsan National Institutes of Science and Technology in South Korea and coworkers noticed that the drugs were not absorbed into mitochondria, a key cellular compartment, and HSPs in this compartment were therefore not being blocked. They identified a new HSP inhibitor that can reach every cellular compartment and inhibit all HSPs. Testing in mice showed that this inhibitor effectively triggered death of tumor cells, and therefore shows promise for anti-cancer therapy. The Hsp90 family proteins Hsp90, Grp94, and TRAP1 are present in the cell cytoplasm, endoplasmic reticulum, and mitochondria, respectively; all play important roles in tumorigenesis by regulating protein homeostasis in response to stress. Thus, simultaneous inhibition of all Hsp90 paralogs is a reasonable strategy for cancer therapy. However, since the existing pan-Hsp90 inhibitor does not accumulate in mitochondria, the potential anticancer activity of pan-Hsp90 inhibition has not yet been fully examined in vivo. Analysis of The Cancer Genome Atlas database revealed that all Hsp90 paralogs were upregulated in prostate cancer. Inactivation of all Hsp90 paralogs induced mitochondrial dysfunction, increased cytosolic calcium, and activated calcineurin. Active calcineurin blocked prosurvival heat shock responses upon Hsp90 inhibition by preventing nuclear translocation of HSF1. The purine scaffold derivative DN401 inhibited all Hsp90 paralogs simultaneously and showed stronger anticancer activity than other Hsp90 inhibitors. Pan-Hsp90 inhibition increased cytotoxicity and suppressed mechanisms that protect cancer cells, suggesting that it is a feasible strategy for the development of potent anticancer drugs. The mitochondria-permeable drug DN401 is a newly identified in vivo pan-Hsp90 inhibitor with potent anticancer activity