We observed that treatment with dimethyl α-ketoglutarate (DMK) increased the amount of intracellular α-ketoglutarate significantly more than that of α-ketoglutarate in HaCaT cells. DMK also increased the level of intracellular 4-hydroxyproline and promoted the production of collagen in HaCaT cells. In addition, DMK decreased the production of collagenase and elastase and downregulated the expression of selected matrix metalloproteinases (MMPs), such as MMP-1, MMP-9, MMP-10, and MMP-12, via transcriptional inhibition. The inhibition of MMPs by DMK was mediated by the suppression of the IL-1 signaling cascade, leading to the attenuation of ERK1/2 phosphorylation and AP-1 transactivation. Our study results illustrate that DMK, an alkylated derivative of α-ketoglutarate, increased the level of 4-hydroxyproline, promoted the production of collagen, and inhibited the expression of selected MMPs by affecting the IL-1 cascade and AP-1 transactivation in HaCaT cells. The results suggest that DMK might be useful as an anti-wrinkle ingredient.

Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disease characterized by spiking fever, arthralgia, skin rashes, and hyperferritinemia. The rash is usually salmon-colored, non-itchy, accompanied by fever, and disappears with an improvement of fever. However, in some cases, the rash persisted regardless of fever. Here, we present a case of AOSD with an atypical persistent rash that showed histological findings resembling those of neutrophilic urticarial dermatosis. The patient was a 60-year-old woman with high fever, arthralgia, and a persistent flagellated skin rash. Despite systemic steroid treatment, the patient developed a serious complication: macrophage activation syndrome. Since this case presented with an atypical persistent rash with histological resemblance to neutrophilic urticarial dermatosis, we report its contribution to the further study of AOSD.

Background and Objectives: We evaluated the effect of adipose-derived stem cell-derived conditioned medium (ADSC-CM) on the renal function of rats with renal ischemia-reperfusion injury (IRI)-induced acute kidney injury. Methods: and Results: Forty male Sprague‐Dawley rats were randomly divided into four groups: sham, nephrectomy control, IRI control, ADSC-CM. The ADSC-CM was prepared using the three-dimensional spheroid culture system and injected into renal parenchyme. The renal function of the rats was evaluated 28 days before and 1, 2, 3, 4, 7, and 14 days after surgical procedures. The rats were sacrificed 14 days after surgical procedures, and kidney tissues were collected for histological examination. The renal parenchymal injection of ADSC-CM significantly reduced the serum blood urea nitrogen and creatinine levels compared with the IRI control group on days 1, 2, 3, and 4 after IRI. The renal parenchymal injection of ADSC-CM significantly increased the level of creatinine clearance compared with the IRI control group 1 day after IRI. Collagen content was significantly lower in the ADSC-CM group than in the IRI control group in the cortex and medulla. Apoptosis was significantly decreased, and proliferation was significantly increased in the ADSC-CM group compared to the IRI control group in the cortex and medulla. The expressions of anti-oxidative makers were higher in the ADSC-CM group than in the IRI control group in the cortex and medulla. Conclusions The renal function was effectively rescued through the renal parenchymal injection of ADSC-CM prepared using a three-dimensional spheroid culture system.

Background: /Aim: Radiotherapy (RT) is an effective local treatment for hepatocellular carcinoma (HCC). However, whether additional RT is safe and effective in patients with advanced HCC receiving atezolizumab plus bevacizumab remains unclear. This retrospective cohort study aimed to evaluate the feasibility of additional RT in these patients. Methods: Between March and October 2021, we retrospectively analyzed seven patients with advanced HCC who received RT during treatment with atezolizumab plus bevacizumab. The median prescribed RT dose was 35 Gy (range, 33–66). Freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) after RT were analyzed. Results: The median follow-up duration after RT was 14.2 months (range, 10.0–18.6). Of the seven patients, disease progression was noted in six (85.7%), the sites of disease progression were local in two (28.6%), intrahepatic in four (57.1%), and extrahepatic in four (57.1%). The median time of FFLP was not reached, and PFS and OS times were 4.0 (95% confidence interval [CI], 3.6–4.5) and 14.8% (95% CI, 12.5–17.2) months, respectively. The 1-year FFLP, PFS, and OS rates were 60% (95% CI, 43.8–76.2), 0%, and 85.7% (95% CI, 75.9–95.5), respectively. Grade 3 or higher hematologic adverse events (AEs) were not observed, but grade 3 nonhematologic AEs unrelated to RT were observed in one patient. Conclusions The addition of RT may be feasible in patients with advanced HCC treated with atezolizumab plus bevacizumab. However, further studies are required to validate these findings.

Background and Objectives: We compared the efficacy and safety of human bone marrow-derived mesenchymal stem cells (hBMSC), delivered at different doses and via different injection routes in an animal model of chronic kidney disease. Methods: and Results: A total of ninety 12-week-old rats underwent 5/6 nephrectomy and randomized among nine groups: sham, renal artery control (RA-C), tail vein control (TV-C), renal artery low dose (RA-LD) (0.5×10 6 cells), renal artery moderate dose (RA-MD) (1.0×10 6 cells), renal artery high dose (RA-HD) (2.0×10 6 cells), tail vein low dose (TV-LD) (0.5×10 6 cells), tail vein moderate dose (TV-MD) (1.0×10 6 cells), and tail vein high dose (TV-HD) (2.0×10 6 cells). Renal function and mortality of rats were evaluated after hBMSC injection. Serum blood urea nitrogen was significantly lower in the TV-HD group at 2 weeks (p＜0.01), 16 weeks (p＜0.05), and 24 weeks (p＜0.01) than in the TV-C group, as determined by one-way ANOVA. Serum creatinine was significantly lower in the TV-HD group at 24 weeks (p＜0.05). At 8 weeks, creatinine clearance was significantly higher in the TV-MD and TV-HD groups (p＜0.01, p＜0.05) than in the TV-C group. In the safety evaluation, we observed no significant difference among the groups. Conclusions Our findings confirm the efficacy and safety of high dose (2×10 6 cells) injection of hBMSC via the tail vein.

Background: Thiazolidinediones (TZDs) have been associated with various safety concerns including weight gain, bladder cancer, and congestive heart failure (CHF). This study evaluated the efficacy and safety of lobeglitazone, a novel TZD in patients with type 2 diabetes mellitus (T2DM) in real practice. Methods: In this non-interventional, multi-center, retrospective, and observational study conducted at 15 tertiary or secondary referral hospitals in Korea, a total of 2,228 patients with T2DM who received lobeglitazone 0.5 mg for more than 1 year were enrolled. Results: Overall adverse events (AEs) occurred in 381 patients (17.10%) including edema in 1.97% (n=44). Cerebrovascular and cardiovascular diseases were identified in 0.81% (n=18) and 0.81% (n=18), respectively. One case of CHF was reported as an AE. Edema occurred in 1.97% (n=44) of patients. Hypoglycemia occurred in 2.47% (n=55) of patients. Fracture occurred in 1.17% (n=26) of all patients. Lobeglitazone significantly decreased HbA1c level, resulting in a mean treatment difference of -1.05%± 1.35% (P<0.001), and decreased total cholesterol, triglyceride, and low-density lipoprotein cholesterol. However, it increased high-density lipoprotein cholesterol, regardless of statin administration. The patients who received lobeglitazone 0.5 mg showed an apparent reduction in glycosylated hemoglobin (HbA1c) from baseline during the first 6 months of treatment. The HbA1c levels remained stable between months 6 and 42. Conclusion Lobeglitazone has long-term safety profile, good glycemic-lowering effect and long-term durability of glycemic control in real-world clinical settings.

Purpose: This study aimed to identify the occupational performance and development needs, and specifically the priority needs, of general hospital nurses according to their career levels so as to help create an effective nursing management competency development program. Methods: This is a cross-sectional study conducted with 203 nurses working at three advanced general hospitals in G metropolitan city and C province. The participants completed a questionnaire about behavioral indicators which measured their nursing management performance and development needs. Their career levels were divided into four. Data were analyzed using t-test, ANOVA, Borich need, and the Locus for Focus model. Results: The mean levels of nursing management performance and competency development needs were 2.78±0.75 and 4.07±0.58, respectively. There was a significant difference in nursing management performance and development needs according to career level (F=6.18, p<.001, F=12.35, p<.001). Priority need analysis showed that level 1, level 2, level 3, level 4 nurses had higher demands for self-development and adaptation to new changes/organizationursing work performance and information management role/creativity development, respectively. Conclusion The findings provide a basis for training systems that differentiate between contents and degrees of nursing management competency based on career level to develop nursing human resources.

Background: Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate- and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy. Methods: This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 μIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 μIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The follow-up period is 5 years. Conclusion The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.

Background: Remdesivir is widely used for the treatment of coronavirus disease 2019 (COVID-19), but controversies regarding its efficacy still remain. Methods: A retrospective cohort study was conducted to evaluate the effect of remdesivir on clinical and virologic outcomes of severe COVID-19 patients from June to July 2020. Primary clinical endpoints included clinical recovery, additional mechanical ventilator (MV) support, and duration of oxygen or MV support. Viral load reduction by hospital day (HD) 15 was evaluated by calculating changes in cycle threshold (Ct) values. Results: A total of 86 severe COVID-19 patients were evaluated including 48 remdesivirtreated patients. Baseline characteristics were not significantly different between the two groups. Remdesivir was administered an average of 7.42 days from symptom onset. The proportions of clinical recovery of the remdesivir and supportive care group at HD 14 (56.3% and 39.5%) and HD 28 (87.5% and 78.9%) were not statistically different. The proportion of patients requiring MV support by HD 28 was significantly lower in the remdesivir group than in the supportive care group (22.9% vs. 44.7%, P = 0.032), and MV duration was significantly shorter in the remdesivir group (average, 1.97 vs. 5.37 days; P = 0.017). Analysis of upper respiratory tract specimens demonstrated that increases of Ct value from HD 1–5 to 11–15 were significantly greater in the remdesivir group than the supportive care group (average, 10.19 vs. 5.36; P = 0.007), and the slope of the Ct value increase was also significantly steeper in the remdesivir group (average, 5.10 vs. 2.68; P = 0.007). Conclusion The remdesivir group showed clinical and virologic benefit in terms of MV requirement and viral load reduction, supporting remdesivir treatment for severe COVID-19.