Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Purpose: This study aimed to assess the feasibility of ultrashort echo time (UTE)-T2* mapping in comparison with T2 mapping for quantitative evaluation of meniscal degeneration. Materials and Methods: This study included 208 menisci of 99 patients (59 women and 40 men, median age 52 years old [16–80 years]) who underwent knee MRI with both standard T2 mapping and UTE-T2* mapping sequences. A radiologist reviewed the images and graded meniscal degeneration according to the morphologic criteria on T2-weighted and proton density-weighted sequences. Manually drawn regions of interest were placed along the outline and hyperintensity subregion within the meniscus, and in the same location on midsagittal images of each T2 and UTE-T2* sequence. Meniscal T2 and T2* values (T2m and T2*m) as well as T2 and T2* values of hyperintensity subregions (T2h, T2*h) were calculated. Results: There was a strong correlation between T2m, T2*m, T2h, and T2*h, and morphological grades (correlation coefficient 0.793–0.943, 95% CI). On morphologic analysis, 50, 52, 50, and 56 menisci were graded as 0, 1, 2, and 3, respectively. T2m, T2*m, T2h, and T2*h were found to be significantly different in all the grades and tended to be higher in the more degraded meniscus (p < 0.001 for both). Mean T2m was 10.78 ± 2.91 ms, 15.81 ± 2.99 ms, 20.26 ± 3.19 ms, and 30.80 ± 7.38 ms and mean T2*m was 7.10 ± 1.12 ms, 9.64 ± 1.27 ms, 12.01 ± 1.58 ms, and 18.98 ± 4.67 ms for grades 0, 1, 2, and 3, respectively. Mean T2h was 20.05 ± 3.67 ms, 24.39 ± 4.73 ms, and 38.92 ± 9.49 ms and mean T2*h was 10.94 ± 1.65 ms, 13.67 ± 2.41 ms, and 22.36 ± 5.20 ms for grades 1, 2, and 3, respectively. Conclusion UTE-T2* mapping was feasible for quantitative evaluation of meniscal degeneration in patients. With a few improvements UTE-T2* mapping is a potential substitute for the standard T2 mapping, with improved efficacy.

Objectives: The Korea Centers for Disease Control and Prevention has published “A Guideline for Unknown Disease Outbreaks (UDO).” The aim of this report was to introduce tabletop exercises (TTX) to prepare for UDO in the future. Methods: The UDO Laboratory Analyses Task Force in Korea Centers for Disease Control and Prevention in April 2018, assigned unknown diseases into 5 syndromes, designed an algorithm for diagnosis, and made a panel list for diagnosis by exclusion. Using the guidelines and laboratory analyses for UDO, TTX were introduced. Results: Since September 9th , 2018, the UDO Laboratory Analyses Task Force has been preparing TTX based on a scenario of an outbreak caused by a novel coronavirus. In December 2019, through TTX, individual missions, epidemiological investigations, sample treatments, diagnosis by exclusions, and next generation sequencing analysis were discussed, and a novel coronavirus was identified as the causal pathogen. Conclusion Guideline and laboratory analyses for UDO successfully applied in TTX. Conclusions drawn from TTX could be applied effectively in the analyses for the initial response to COVID-19, an ongoing epidemic of 2019 - 2020. Therefore, TTX should continuously be conducted for the response and preparation against UDO.

Fimasartan, a new angiotensin II receptor antagonist, reduces myocyte damage and stabilizes atherosclerotic plaque through its anti-inflammatory effect in animal studies. We investigated the protective effects of pretreatment with fimasartan on ischemia-reperfusion injury (IRI) in a mouse model of ischemic renal damage. C57BL/6 mice were pretreated with or without 5 (IR-F5) or 10 (IR-F10) mg/kg/day fimasartan for 3 days. Renal ischemia was induced by clamping bilateral renal vascular pedicles for 30 min. Histology, pro-inflammatory cytokines, and apoptosis assays were evaluated 24 h after IRI. Compared to the untreated group, blood urea nitrogen and serum creatinine levels were significantly lower in the IR-F10 group. IR-F10 kidneys showed less tubular necrosis and interstitial fibrosis than untreated kidneys. The expression of F4/80, a macrophage infiltration marker, and tumor necrosis factor (TNF)-α, decreased in the IR-F10 group. High-dose fimasartan treatment attenuated the upregulation of TNF-α, interleukin (IL)-1β, and IL-6 in ischemic kidneys. Fewer TUNEL positive cells were observed in IR-F10 compared to control mice. Fimasartan caused a significant decrease in caspase-3 activity and the level of Bax, and increased the Bcl-2 level. Fimasartan preserved renal function and tubular architecture from IRI in a mouse ischemic renal injury model. Fimasartan also attenuated upregulation of inflammatory cytokines and decreased apoptosis of renal tubular cells. Our results suggest that fimasartan inhibited the process of tubular injury by preventing apoptosis induced by the inflammatory pathway.
Animals ; Apoptosis* ; Blood Urea Nitrogen ; Caspase 3 ; Constriction ; Creatinine ; Cytokines ; Fibrosis ; In Situ Nick-End Labeling ; Interleukin-6 ; Interleukins ; Ischemia ; Kidney ; Macrophages ; Mice ; Muscle Cells ; Necrosis ; Plaque, Atherosclerotic ; Receptors, Angiotensin ; Reperfusion Injury* ; Tumor Necrosis Factor-alpha ; Up-Regulation

PURPOSE: To evaluate the therapeutic effect of human embryonic stem cell (hESC)-derived multipotent mesenchymal stem cells (M-MSCs) on ketamine-induced cystitis (KC) in rats. METHODS: To induce KC, 10-week-old female rats were injected with 25-mg/kg ketamine hydrochloride twice weekly for 12 weeks. In the sham group, phosphate buffered saline (PBS) was injected instead of ketamine. One week after the final injection of ketamine, the indicated doses (0.25, 0.5, and 1×106 cells) of M-MSCs (KC+M-MSC group) or PBS vehicle (KC group) were directly injected into the bladder wall. One week after M-MSC injection, the therapeutic outcomes were evaluated via cystometry, histological analyses, and measurement of gene expression. Next, we compared the efficacy of M-MSCs at a low dose (1×105 cells) to that of an identical dose of adult bone marrow (BM)-derived MSCs. RESULTS: Rats in the KC group exhibited increased voiding frequency and reduced bladder capacity compared to rats of the sham group. However, these parameters recovered after transplantation of M-MSCs at all doses tested. KC bladders exhibited markedly increased mast cell infiltration, apoptosis, and tissue fibrosis. Administration of M-MSCs significantly reversed these characteristic histological alterations. Gene expression analyses indicated that several genes associated with tissue fibrosis were markedly upregulated in KC bladders. However the expression of these genes was significantly suppressed by the administration of M-MSCs. Importantly, M-MSCs ameliorated bladder deterioration in KC rats after injection of a low dose (1×105) of cells, at which point BM-derived MSCs did not substantially improve bladder function. CONCLUSIONS: This study demonstrates for the first time the therapeutic efficacy of hESC-derived M-MSCs on KC in rats. M-MSCs restored bladder function more effectively than did BM-derived MSCs, protecting against abnormal changes including mast cell infiltration, apoptosis and fibrotic damage.
Adult ; Animals ; Apoptosis ; Bone Marrow ; Cystitis ; Female ; Fibrosis ; Gene Expression ; Human Embryonic Stem Cells ; Humans ; Ketamine ; Mast Cells ; Mesenchymal Stromal Cells ; Multipotent Stem Cells ; Pelvic Pain ; Rats ; Urinary Bladder

BACKGROUND: Bile acids have anti-cancer properties in a certain types of cancers. We determined anticancer activity and its underlying molecular mechanism of ursodeoxycholic acid (UDCA) in human DU145 prostate cancer cells. METHODS: Cell viability was measured with an MTT assay. UDCA-induced apoptosis was determined with flow cytometric analysis. The expression levels of apoptosis-related signaling proteins were examined with Western blotting. RESULTS: UDCA treatment significantly inhibited cell growth of DU145 in a dose-dependent manner. It induced cellular shrinkage and cytoplasmic blebs and accumulated the cells with sub-G1 DNA contents. Moreover, UDCA activated caspase 8, suggesting that UDCA-induced apoptosis is associated with extrinsic pathway. Consistent to this finding, UDCA increased the expressions of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor, death receptor 4 (DR4) and death receptor 5 (DR5), and TRAIL augmented the UDCA-induced cell death in DU145 cells. In addition, UDCA also increased the expressions of Bax and cytochrome c and decreased the expression of Bcl-xL in DU145 cells. This finding suggests that UDCA-induced apoptosis may be involved in intrinsic pathway. CONCLUSIONS: UDCA induces apoptosis via extrinsic pathway as well as intrinsic pathway in DU145 prostate cancer cells. UDCA may be a promising anti-cancer agent against prostate cancer.
Apoptosis* ; Bile Acids and Salts ; Blister ; Blotting, Western ; Caspase 8 ; Cell Death ; Cell Survival ; Cytochromes c ; Cytoplasm ; DNA ; Humans ; Necrosis ; Prostate* ; Prostatic Neoplasms* ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; Ursodeoxycholic Acid*

This study explored epidemiological trends in trichomoniasis in Daegu, South Korea. Wet mount microscopy, PCR, and multiplex PCR were used to test for Trichomonas vaginalis in vaginal swab samples obtained from 621 women visiting 2 clinics in Daegu. Of the 621 women tested, microscopy detected T. vaginalis in 4 (0.6%) patients, PCR detected T. vaginalis in 19 (3.0%) patients, and multiplex PCR detected T. vaginalis in 12 (1.9%) patients. Testing via PCR demonstrated high sensitivity and high negative predictive value for T. vaginalis. Among the 19 women who tested positive for T. vaginalis according to PCR, 94.7% (18/19) reported vaginal signs and symptoms. Notably, more than 50% of T. vaginalis infections occurred in females younger than 30 years old, and 58% were unmarried. Multiplex PCR, which simultaneously detects pathogens from various sexually transmitted infections, revealed that 91.7% (11/12) of patients were infected with 2 or more pathogens. Mycoplasma hominis was the most prevalent co-infection pathogen with T. vaginalis, followed by Ureaplasma urealyticum and Chlamydia trachomatis. Our results indicate that PCR and multiplex PCR are the most sensitive tools for T. vaginalis diagnosis, rather than microscopy which has been routinely used to detect T. vaginalis infections in South Korea. Therefore, clinicians should take note of the high prevalence of T. vaginalis infections among adolescent and young women in order to prevent persistent infection and transmission of this disease.
Adolescent ; Adult ; Ambulatory Care Facilities/statistics & numerical data ; Female ; Humans ; Microscopy/standards ; Middle Aged ; Multiplex Polymerase Chain Reaction/standards ; Polymerase Chain Reaction/standards ; Predictive Value of Tests ; Prevalence ; Republic of Korea/epidemiology ; Sensitivity and Specificity ; Trichomonas Infections/*epidemiology/prevention & control ; Trichomonas vaginalis/physiology ; Vaginal Smears/standards ; Young Adult

PURPOSE: There is no regimen that is strongly recommended for more than second-line treatment. We investigated the efficacy and safety of platinum/vinorelbine as more than second-line treatment. MATERIALS AND METHODS: We selected patients with advanced non-small cell lung cancer (NSCLC) who received treatment with platinum/vinorelbine at Chungnam National University Hospital from August 2001 to December 2013. The primary end point was the response rate, and secondary end points were progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: Thirty-five patients were enrolled. Response rate was 22.9% (complete response, 0 patients [0%]; partial response, eight patients [22.9%]; stable disease, 10 patients [28.6%]; progressive disease, 14 patients [40.0%]). A significantly higher response rate was observed for patients who had responded to previous chemotherapy than for those who did not (34.8% [8/23] vs. 0% [0/12], p=0.020). The median PFS was 4 months (range, 1 to 21 months). Patients with adenocarcinoma and non-smokers had a significantly longer PFS than patients with non-adenocarcinoma and smokers (5 months vs. 2 months, p=0.007; 4.5 months vs. 2 months, p=0.046, respectively). The median OS was 10 months (range, 1 to 41 months). Patients with good performance status and non-smokers had a significantly longer OS than patients with poor performance status and smokers (14 months vs. 4 months, p=0.02; 18.5 months vs. 6 months, p=0.049, respectively). The main serious adverse event (grade 3 or 4) was neutropenia (15 events, 13.3%) in a total of 113 cycles. CONCLUSION: Platinum/vinorelbine was effective as more than second-line chemotherapy, and the toxicity was tolerable, in patients with advanced NSCLC.
Adenocarcinoma ; Carcinoma, Non-Small-Cell Lung* ; Chungcheongnam-do ; Disease-Free Survival ; Drug Therapy* ; Humans ; Neutropenia

BACKGROUND: Cisplatin (cis-diaminedichloroplatinum, CDDP) is a widely used chemotherapeutic agent for the treatment of many cancers. However, initial resistance to CDDP is a serious problem in treating these cancers. Vitis coignetiae Pulliat (Meoru in Korea) have shown anti-nuclear factor kappa B and anti-epidermal growth factor receptor activities in cancer cells. METHODS: In this study, in order to seeking an approach to increase the anti-cancer effects of CDDP with natural products. Here, we investigated anthocyanins isolated from Vitis coignetiae Pulliat (anthocyanidins isolated from meoru, AIMs) can enhance anti-cancer effects of cisplatin (CDDP) in stomach cancer cells. The cell viability of SNU-1 and SNU-16 cells after treated with AIMs and CDDP were analyzed by MTT assay. The expressions of Akt and X-linked inhibitor of apoptosis protein (XIAP) proteins were examined by western blot in AIMs- and CDDP-treated cells. RESULTS: We found that AIMs enhanced anticancer effects of CDDP, which activity was additive but not synergistic. AIMs suppressed Akt activity of the cancer cells activated by CDDP. AIMs also suppressed in XIAP an anti-apoptotic protein. CONCLUSIONS: This study suggests that the anthocyanins isolated from fruits of Vitis coignetiae Pulliat enhanced anti-cancer effects of CDDP by inhibiting Akt activity activated by CDDP.
Anthocyanins* ; Biological Products ; Blotting, Western ; Cell Survival ; Cisplatin* ; Fruit* ; Humans* ; Stomach Neoplasms* ; Vitis* ; X-Linked Inhibitor of Apoptosis Protein

Thromboembolic events are rare among systemic complications of inflammatory bowel disease; however, they are a significant cause of mortality when they occur. Several reports have considered thromboembolic events in patients with ulcerative colitis presenting with venous or arterial thromboembolism, such as cerebral thrombosis, deep vein thrombosis, pulmonary thromboembolism, portal vein thrombosis, or mesenteric vein thrombosis. However, increased coagulability related to Crohn's disease is extremely rare compared with that of ulcerative colitis. We report a case of a 42-year-old man with complicated portal hypertension that occurred due to extensive portal vein and mesenteric vein thrombosis. He had a monozygotic twin brother who was also in remission with Crohn's disease. The patient showed protein C and protein S deficiencies; however, he recovered with early anticoagulation therapy.
Colitis, Ulcerative ; Crohn Disease ; Humans ; Hypertension, Portal ; Intracranial Thrombosis ; Mesenteric Veins ; Portal Vein ; Protein C ; Protein S ; Pulmonary Embolism ; Siblings ; Thromboembolism ; Thrombosis ; Twins, Monozygotic ; Venous Thromboembolism ; Venous Thrombosis