BACKGROUND/OBJECTIVES: Orostachys japonicus A. Berger (O. japonicus) is a perennial herb belonging to the Crassulaceae family that has been traditionally used to treat inflammation, fever, and poisoning. Although studies on the anticancer activity of O. japonicus have been conducted, its effect on virus-induced cancers has yet to be elucidated.MATERIALS/METHODS: In the present study, we investigated the effects and mechanisms of action of the ethyl acetate fraction of O. japonicus extract (E-OJ) on the viability and apoptosis of HeLa cervical cancer cells. RESULTS: The effect of E-OJ on HeLa cells was compared to that of kaempferol, quercetin, and gallic acid, which are components of O. japonicus. Treatment with E-OJ induced a concentration-dependent decrease in cell viability, as confirmed by MTS assay. Pretreatment with a broad-spectrum caspase inhibitor resulted in the recovery of cell viability. Western blot analysis was conducted to determine whether the induction of apoptosis was caspasedependent. E-OJ induced apoptosis by increasing Bax/Bcl-2 ratio. Furthermore, it modulated the levels of cleaved caspase-3, -8, and -9, indicative of an impact on both the intrinsic and extrinsic pathways of apoptosis. Pretreatment with caspase inhibitors reduced caspase activity. CONCLUSION These results suggest that the anticancer activity of O. japonicus is mediated by caspases, resulting in a decrease in the viability of HeLa cells.

BACKGROUND/OBJECTIVES: Orostachys japonicus A. Berger (O. japonicus) is a perennial herb belonging to the Crassulaceae family that has been traditionally used to treat inflammation, fever, and poisoning. Although studies on the anticancer activity of O. japonicus have been conducted, its effect on virus-induced cancers has yet to be elucidated.MATERIALS/METHODS: In the present study, we investigated the effects and mechanisms of action of the ethyl acetate fraction of O. japonicus extract (E-OJ) on the viability and apoptosis of HeLa cervical cancer cells. RESULTS: The effect of E-OJ on HeLa cells was compared to that of kaempferol, quercetin, and gallic acid, which are components of O. japonicus. Treatment with E-OJ induced a concentration-dependent decrease in cell viability, as confirmed by MTS assay. Pretreatment with a broad-spectrum caspase inhibitor resulted in the recovery of cell viability. Western blot analysis was conducted to determine whether the induction of apoptosis was caspasedependent. E-OJ induced apoptosis by increasing Bax/Bcl-2 ratio. Furthermore, it modulated the levels of cleaved caspase-3, -8, and -9, indicative of an impact on both the intrinsic and extrinsic pathways of apoptosis. Pretreatment with caspase inhibitors reduced caspase activity. CONCLUSION These results suggest that the anticancer activity of O. japonicus is mediated by caspases, resulting in a decrease in the viability of HeLa cells.

Radiofrequency ablation (RFA) is a minimally invasive treatment modality used as an alternative to surgery in patients with benign thyroid nodules, recurrent thyroid cancers (RTCs), and primary thyroid microcarcinomas. The Korean Society of Thyroid Radiology (KSThR) initially developed recommendations for the optimal use of RFA for thyroid tumors in 2009 and revised them in 2012 and 2017. As new meaningful evidence has accumulated since 2017 and in response to a growing global interest in the use of RFA for treating malignant thyroid lesions, the task force committee members of the KSThR decided to update the guidelines on the use of RFA for the management of RTCs based on a comprehensive analysis of current literature and expert consensus.

Objective: Deficits in social cognition (mentalization) and other cognitive deficits have been reported in patients with major depressive disorder (MDD) and may influence treatment response. This study examined the impact of cognitive function on treatment response of patients with MDD after 8 weeks of medication and whether the impact was mediated by mentalization. Methods: Cognitive function (memory, attention, executive function, processing speed) and mentalization were measured in 28 patients with MDD at baseline using neuropsychological tests and self-report scales. The treatment response was defined as the rate of improvement in symptom severity and global function. Results: Multiple regression analyses, controlling for mentalization and cognitive function, separately revealed that delayed recall was a negative predictor of functional improvement after 8 weeks of treatment, while mentalization was a positive predictor. A single mediation model using PROCESS macro showed that delayed recall and Digit Span backward indirectly affected functional improvement, mediated by mentalization. When age at onset was controlled for as a covariate, the mediating effect lost significance, and the direct effect of delayed recall on functional improvement was still significant. Conclusion Despite the small sample size, our results provide evidence that patients with MDD and low memory (delayed recall) at baseline may benefit more from short-term pharmacological treatments.

Auricular vagus nerve stimulation (aVNS) is one of the promising neuromodulation techniques due to its non-invasiveness, convenience, and effectiveness. aVNS has been suggested as a potential treatment for neurodegenerative diseases showing impaired cerebrospinal fluid (CSF) dynamics. Improving CSF flow has been proposed as a key mechanism of the therapeutic effect on neurodegenerative diseases. However, aVNS parameters have been set empirically and the effective parameter that maximize the effect remains elusive. Here we show that 30 minutes of low-frequency aVNS increased arterial vasomotion events and enhanced cortical CSF influx along the branches of middle cerebral arteries. By using in vivo two photon imaging or widefield fluorescence microscopy with plasma and CSF tracers for visualizing blood vessels and perivascular spaces, arterial vasomotion and cortical CSF influx dynamics were acquired. The low-frequency (2 Hz) aVNS, but not middleand high-frequency (40 and 100 Hz) aVNS, significantly increased the number of vasomotion events compared to the sham group. Accordingly, in the CSF imaging, 2 Hz of aVNS markedly enhanced the CSF influx. Our findings demonstrate that lowfrequency aVNS is the effective parameter in respect to modulating vasomotion and CSF influx, resulting in brain clearance effect.

Background: Primary Merkel cell carcinoma of the salivary gland is currently not listed in the World Health Organization classification. However, cases of Merkel cell type neuroendocrine carcinomas of the salivary gland with perinuclear cytokeratin 20 positivity have been intermittently reported. We here investigated the clinicopathologic features of additional cases. Methods: Data of four cases of Merkel cell type small cell neuroendocrine carcinoma of the salivary gland were retrieved. To confirm the tumors’ primary nature, clinical records and pathologic materials were reviewed. Optimal immunohistochemical staining was performed to support the diagnosis. Results: All tumors were located in the parotid gland. Possibilities of metastasis were excluded in all cases through a meticulous clinicopathological review. Tumor histology was consistent with the diagnosis of small cell neuroendocrine carcinoma. Tumors’ immunohistochemical phenotypes were consistent with Merkel cell carcinoma, including Merkel cell polyomavirus large T antigen positivity in two of the four cases. Conclusions Merkel cell carcinomas can originate in salivary glands and are partly associated with Merkel cell polyomavirus infection as in cutaneous Merkel cell carcinomas.

Background: Complete revascularization has demonstrated better outcomes in patients with acute myocardial infarction (AMI) and multivessel disease. However, in the case of left main (LM) culprit lesion AMI with multivessel disease, there is limited evidence to suggest that complete revascularization is better. Methods: We reviewed 16,831 patients in the Korea Acute Myocardial Infarction Registry who were treated from July 2016 to June 2020, and 399 patients were enrolled with LM culprit lesion AMI treated with percutaneous coronary intervention. We categorized the patients as those treated with complete revascularization (n=295) or incomplete revascularization (n=104). The study endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, myocardial infarction, ischemia-driven revascularization, stent thrombosis, and stroke. We performed propensity score matching (PSM) and analyzed the incidence of MACCE at 1 year. Results: After PSM, the two groups were well balanced. There was no significant difference between the two groups in MACCE at 1 year (12.1% vs. 15.2%; hazard ratio, 1.28; 95% confidence interval, 0.60–2.74; p=0.524) after PSM. The components of MACCE and major bleeding were also not significantly different. Conclusion There was no significant difference in clinical outcomes between the groups treated with complete or incomplete revascularization for LM culprit lesion AMI with multivessel disease.

Objective: This study investigated how educational levels modify the relationship between the standard deviation of NN intervals (SDNN) of heart rate variability and the development of post-traumatic stress disorder (PTSD). Methods: Participants with physical injuries were enrolled from a trauma center and monitored over two years. Initial assessments included SDNN and educational attainment, along with socio-demographic and clinical variables. PTSD diagnoses were made at 3, 6, 12, and 24 months post-injury using the Clinician-Administered PTSD Scale for DSM-5.Logistic regression analyses were conducted. Results: Of the 538 participants, 58 (10.8%) developed PTSD during the follow-up period. A significant interaction effect was observed: lower SDNN was significantly linked to PTSD in individuals with higher education, but not in those with lower education. Conclusion The study identified education-dependent associations between SDNN and PTSD development, emphasizing the importance of tailored PTSD prevention strategies that consider both SDNN and educational levels.

Background/Aims: This study aimed to evaluate the performance of the Model for End-Stage Liver Disease (MELD) 3.0 for predicting mortality and liver-related complications compared with the Child-Pugh classification, albumin-bilirubin (ALBI) grade, the MELD, and the MELD sodium (MELDNa) score. Methods: We evaluated a multicenter retrospective cohort of incorporated patients with cirrhosis between 2013 and 2019. We conducted comparisons of the area under the receiver operating characteristic curve (AUROC) of the MELD3.0 and other models for predicting 3-month mortality. Additionally, we assessed the risk of cirrhosis-related complications according to the MELD3.0 score. Results: A total of 3,314 patients were included. The mean age was 55.9±11.3 years, and 70.2% of the patients were male. Within the initial 3 months, 220 patients (6.6%) died, and the MELD3.0had the best predictive performance among the tested models, with an AUROC of 0.851, outperforming the Child-Pugh classification, ALBI grade, MELD, and MELDNa. A high MELD3.0score was associated with an increased risk of mortality. Compared with that of the group with a MELD3.0 score <10 points, the adjusted hazard ratio of the group with a score of 10–20 pointswas 2.176, and that for the group with a score of ≥20 points was 4.892. Each 1-point increase inthe MELD3.0 score increased the risk of cirrhosis-related complications by 1.033-fold. The risk of hepatorenal syndrome showed the highest increase, with an adjusted hazard ratio of 1.149, followed by hepatic encephalopathy and ascites. Conclusions The MELD3.0 demonstrated robust prognostic performance in predicting mortality in patients with cirrhosis. Moreover, the MELD3.0 score was linked to cirrhosis-related complications, particularly those involving kidney function, such as hepatorenal syndrome and ascites.

Background/Aims: The Korean guidelines for Helicobacter pylori treatment were revised in 2020, however, the extent of adherence to these guidelines in clinical practice remains unclear. Herein, we initiated a prospective, nationwide, multicenter registry study in 2021 to evaluate the current management of H.pylori infection in Korea. Methods: This interim report describes the adherence to the revised guidelines and their impact on firstline eradication rates. Data on patient demographics, diagnoses, treatments, and eradication outcomes were collected using a web-based electronic case report form. Results: A total of 7,261 patients from 66 hospitals who received first-line treatment were analyzed.The modified intention-to-treat eradication rate for first-line treatment was 81.0%, with 80.4% of the prescriptions adhering to the revised guidelines. The most commonly prescribed regimen was the 14-day clarithromycin-based triple therapy (CTT; 42.0%), followed by tailored therapy (TT; 21.2%), 7-day CTT (14.1%), and 10-day concomitant therapy (CT; 10.1%). Time-trend analysis demonstrated significant increases in guideline adherence and the use of 10-day CT and TT, along with a decrease in the use of 7-day CTT (all p<0.001). Multivariate logistic regression analysis revealed that guideline adherence was significantly associated with first-line eradication success (odds ratio, 2.03; 95% confidence interval, 1.61 to 2.56; p<0.001). Conclusions The revised guidelines for the treatment of H. pylori infection have been increasingly adopted in routine clinical practice in Korea, which may have contributed to improved first-line eradication rates. Notably, the 14-day CTT, 10-day CT, and TT regimens are emerging as the preferred first-line treatment options among Korean physicians.