Development and Effectiveness Verification of Metaverse Cognitive Therapy Contents for MCI Patients.

It is very important to prevent dementia by intervening in advance in the stage of mild cognitive impairment, which is the pre-stage of dementia. Recently, cognitive therapy research using metaverse has been on the rise. We propose a way to utilize metaverse cognitive therapy content as a non-drug treatment method of mild cognitive impairment patients. This paper shows the results of clinical trials using metaverse cognitive therapy contents developed by us. We collected data from MCI patient groups and normal groups through MMSE-KC tests and in-content data collection systems. We conducted paired t-tests and repeat measurement ANOVA based on the collected data. The results of this study show how metaverse cognitive therapy content affects MCI patients, and suggest various factors to be considered when creating functional content.

Everolimus Plus Ku0063794 Regimen Promotes Anticancer Effects against Hepatocellular Carcinoma Cells through the Paradoxical Inhibition of Autophagy.

PURPOSE: Everolimus only inhibits mammalian target of rapamycin complex 1 (mTORC1), whereas Ku0063794 inhibits both mTORC1 and mTORC2. Although they have similar anticancer effects, their combination has a synergistic effect against hepatocellular carcinoma (HCC) cells. We aimed to determine the mechanism underlying the synergistic effects of everolimus and Ku0063794 associated with autophagy in HCC cells. MATERIALS AND METHODS: We compared the effects of everolimus and Ku0063794, individually or in combination, on both the in vitro and in vivo models of HCCs. RESULTS: HepG2 cells treated with both agents had significantly lower rates of cell proliferation and higher apoptosis than the individual monotherapies (p < 0.05). Autophagic studies consistently indicated that, unlike the monotherapies, the combination therapy significantly reduced autophagy (p < 0.05). Autophagic blockage directly promoted the pro-apoptotic effects of combination therapy, suggesting autophagy as the survival mechanism of HCC cells. Unlike the monotherapies, combination therapy showed the potential to inhibit sirtuin 1 (SIRT1), the positive regulator of autophagy. SIRT1 overexpression abrogated the autophagy-inhibiting and pro-apoptotic effects of combination therapy. In a nude mouse xenograft model, the shrinkage of tumors was more prominent in mice treated with combination therapy than in mice treated with the respective monotherapies (p < 0.05). The immunohistochemical and immunofluorescence stains of the tumor obtained from the xenograft model showed that combination therapy had the potential of reducing autophagy and promoting apoptosis. CONCLUSION: The combination of everolimus and Ku0063794 potentiates anticancer effects on HCCs through a decrease in autophagy, which is prompted by SIRT1 downregulation.

HSP90 inhibitor 17-DMAG exerts anticancer effects against gastric cancer cells principally by altering oxidant-antioxidant balance.

Heat shock protein 90 (HSP90) stabilizes numerous oncoproteins and, therefore, its inhibition has emerged as a promising antineoplastic strategy for diverse malignancies. In this study, we determined the therapeutic effects and mechanisms of action of a specific HSP90 inhibitor, 17-dimethylamino-ethylamino-17-demethoxygeldanamycin (17-DMAG), in gastric cancer cell lines (AGS, SNU-1, and KATO-III), patient-derived tissues, and a mouse xenograft model. 17-DMAG exerted anticancer effects against gastric cancer cells, manifested by significantly decreased proliferation rates (P < 0.05) and increased expression of apoptotic markers. Flow cytometry using dichlorofluorescein (DCF) diacetate revealed that 17-DMAG dose-dependently increases reactive oxygen species (ROS) levels in gastric cancer cells. Inhibition of ROS by N-acetyl-L-cysteine (NAC) abrogated the proapoptotic effects of 17-DMAG, as demonstrated by the decreased expression of proapoptotic proteins. In addition, 17-DMAG dose- and time-dependently reduced the expression of antioxidants such as catalase and glutathione peroxidase (GPx). Moreover, 17-DMAG reduced the expression of nuclear respiratory factor (NRF)-1 and NRF-2, and prevented them from migrating from the cytoplasm to the nucleus dose-dependently. Finally, in a nude mouse xenograft model, the shrinkage of tumors was more prominent in mice treated with 17-DMAG than in control mice (P < 0.05). Taken altogether, our results suggest that 17-DMAG exerts potent antineoplastic activity against gastric cancer cells primarily by promoting ROS generation and suppressing antioxidant enzyme activities.

Determination of optimized oxygen partial pressure to maximize the liver regenerative potential of the secretome obtained from adipose-derived stem cells.

BACKGROUND: A hypoxic-preconditioned secretome from stem cells reportedly promotes the functional and regenerative capacity of the liver more effectively than a control secretome. However, the optimum oxygen partial pressure (pO2) in the cell culture system that maximizes the therapeutic potential of the secretome has not yet been determined. METHODS: We first determined the cellular alterations in adipose tissue-derived stem cells (ASCs) cultured under different pO2 (21%, 10%, 5%, and 1%). Subsequently, partially hepatectomized mice were injected with the secretome of ASCs cultured under different pO2, and then sera and liver specimens were obtained for analyses. RESULTS: Of all AML12 cells cultured under different pO2, the AML12 cells cultured under 1% pO2 showed the highest mRNA expression of proliferation-associated markers (IL-6, HGF, and VEGF). In the cell proliferation assay, the AML12 cells cultured with the secretome of 1% pO2 showed the highest cell proliferation, followed by the cells cultured with the secretome of 21%, 10%, and 5% pO2, in that order. When injected into the partially hepatectomized mice, the 1% pO2 secretome most significantly increased the number of Ki67-positive cells, reduced serum levels of proinflammatory mediators (IL-6 and TNF-α), and reduced serum levels of liver transaminases. In addition, analysis of the liver specimens indicated that injection with the 1% pO2 secretome maximized the expression of the intermediate molecules of the PIP3/Akt and IL-6/STAT3 signaling pathways, all of which are known to promote liver regeneration. CONCLUSIONS: The data of this study suggest that the secretome of ASCs cultured under 1% pO2 has the highest liver reparative and regenerative potential of all the secretomes tested here.

Does Korea's current diagnosis-related group-based reimbursement system appropriately classify appendectomy patients?

PURPOSE: As several years have passed since the implementation of the Korean diagnosis-related group (DRG) payment system for appendicitis, its early outcomes should be assessed to determine if further improvements are warranted. METHODS: We retrospectively analyzed clinical data from Korean patients who underwent appendectomy, dividing the sample into 2 groups of those who received services before and after implementation of the DRG system. Based on the DRG code classification, patient data were collected including the amount of DRG reimbursement and the total in-patient costs. We subsequently performed univariate and multivariate analyses to identify independent factors contributing to higher total in-patient cost. RESULTS: Although implementation of the DRG system for appendicitis significantly reduced postoperative length of stay (2.8 ± 1.0 days vs. 3.4 ± 1.9 days, P < 0.001), it did not reduce total in-hospital cost. The independent factors related to total inhospital cost included patient age of 70 years or more (odds ratio [OR], 3.214; 95% confidence interval [CI], 1.769-5.840; P < 0.001) and operation time longer than 100 minutes (OR, 3.690; 95% CI, 2.007-6.599, P < 0.001). In addition, older patients (≥70 years) showed a nearly 10 times greater relative risk for having a comorbid condition (95% CI, 5.141-20.214; P < 0.001) and a 3.255 times greater relative risk for having higher total in-hospital cost (95% CI, 1.731-6.119, P < 0.001). CONCLUSION: It appears that older patients (>70 years) have greater comorbidities, which contribute to higher inpatient costs. Thus, our study suggests that patient age be considered as a DRG classification variable.

The feasibility of single-port laparoscopic appendectomy using a solo approach: a comparative study.

PURPOSE: To investigate the feasibility and safety of solo surgery with single-port laparoscopic appendectomy, which is termed herein solo-SPLA (solo-single-port laparoscopic appendectomy). METHODS: This study prospectively collected and retrospectively analyzed data from patients who had undergone either non-solo-SPLA (n = 150) or solo-SPLA (n = 150). Several devices were utilized for complete, skin-to-skin solo-SPSA, including a Lone Star Retractor System and an adjustable mechanical camera holder. RESULTS: Operating times were not significantly different between solo- and non-solo-SPLA (45.0 ± 21.0 minutes vs. 46.7 ± 26.1 minutes, P = 0.646). Most postoperative variables were also comparable between groups, including the necessity for intravenous analgesics (0.7 ± 1.2 ampules [solo-SPLA] vs. 0.9 ± 1.5 ampules [non-solo-SPLA], P = 0.092), time interval to gas passing (1.3 ± 1.0 days vs. 1.4 ± 1.0 days, P = 0.182), and the incidence of postoperative complications (4.0% vs. 8.7%, P = 0.153). Moreover, solo-SPLA effectively lowered the operating cost by reducing surgical personnel expenses. CONCLUSION: Solo-SPLA economized staff numbers and thus lowered hospital costs without lengthening of operating time. Therefore, solo-SPLA could be considered a safe and feasible alternative to non-solo-SPLA.