Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.

Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.

Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.

Background: Alcoholic liver disease (ALD) includes a wide clinical spectrum from acute alcoholic hepatitis to severe cirrhosis and/or hepatocellular carcinoma. Until now, there has been no report revealing the bleeding tendency of ALD compared to other diseases in liver transplantation (LT). Thus, we analyzed blood loss and transfusion amounts during operation according to the etiologies of liver disease and model for end-stage liver disease (MELD) score. Methods: Out of 874 recipients who underwent LT, a total of 146 patients were excluded by our exclusion criteria. We compared 728 recipients’ baseline characteristics, operation time, blood loss, and transfusion amounts between ALD and nonALD according to MELD score. Results: The number of patients in the ALD group was 130 (17.9%), and 598 (82.1%) in the non-ALD group. The ALD group showed younger age, higher MELD score, and a higher proportion of deceased donor LT than the non-ALD group. Intraoperative blood loss and transfusions of red blood cells (RBCs), fresh frozen plasma, and platelets were significantly higher in the ALD group. When stratified by MELD score (cut-off: 20), ALD patients in both high and low MELD subgroups demonstrated greater blood loss and RBC transfusion requirements, even when international normalized ratio and platelet counts were similar. In multivariate logistic regression analysis, ALD was a significant risk factor for massive transfusion (odds ratio 1.813, 95% confidence interval 1.158–2.840, p=0.009). Conclusion The ALD group showed increased bleeding tendency than the non-ALD group during LT, irrespective of MELD score. This suggests that transplant surgeons should anticipate greater blood loss and ensure adequate transfusion resources during LT for ALD patients.

Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents.. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients’ values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.

Background and Objectives: Cognitive behavioral therapy (CBT) is a treatment option for subjective tinnitus. There are many reports on its clinical efficacy, but the protocol has not been well established. The purpose of this study was to set an outpatient-based CBT protocol and evaluate its clinical efficacy for tinnitus.Subjects and Method A total of 85 chronic tinnitus patients was assessed in this prospective study. After evaluating for eligibility, 30 patients completed CBT based on a protocol of 5 weekly sessions in an outpatient setting. Therapeutic efficacy was assessed by Tinnitus Handicap Inventory (THI) questionnaires and visual analogue scale (VAS) for tinnitus. The initial scores were compared with the final scores, which were assessed a month after the fifth CBT session. Results: The results showed that CBT reduced THI and VAS scores significantly (p<0.05). Conclusion The results of the study suggest that an outpatient-based CBT protocol can be clinically beneficial for patients with tinnitus.

Obstructive sleep apnea (OSA) is a common disorder characterized by upper airway obstruction during sleep. To reduce the morbidity of OSA, sleep specialists have explored various methods of managing the condition, including manifold positive airway pressure (PAP) techniques and surgical procedures. Nasal obstruction can cause significant discomfort during sleep, and it is likely that improving nasal obstruction would enhance the quality of life and PAP compliance of OSA patients. Many reliable studies have offered evidence to support this assumption. However, few comprehensive guidelines for managing OSA through nasal surgery encompass all this evidence. In order to address this gap, the Korean Society of Otorhinolaryngology-Head and Neck Surgery (KORL-HNS) and the Korean Society of Sleep and Breathing designated a guideline development group (GDG) to develop recommendations for nasal surgery in OSA patients. Several databases, including OVID Medline, Embase, the Cochrane Library, and KoreaMed, were searched to identify all relevant papers using a predefined search strategy. The types of nasal surgery included septoplasty, turbinate surgery, nasal valve surgery, septorhinoplasty, and endoscopic sinus surgery. When insufficient evidence was found, the GDG sought expert opinions and attempted to fill the evidence gap. Evidence-based recommendations for practice were ranked according to the American College of Physicians’ grading system. The GDG developed 10 key action statements with supporting text to support them. Three statements are ranked as strong recommendations, three are only recommendations, and four can be considered options. The GDG hopes that this clinical practice guideline will help physicians make optimal decisions when caring for OSA patients. Conversely, the statements in this guideline are not intended to limit or restrict physicians’ care based on their experience and assessment of individual patients.

Background: Current international guidelines recommend against deep sedation as it is associated with worse outcomes in the intensive care unit (ICU). However, in Korea the prevalence of deep sedation and its impact on patients in the ICU are not well known. Methods: From April 2020 to July 2021, a multicenter, prospective, longitudinal, noninterventional cohort study was performed in 20 Korean ICUs. Sedation depth extent was divided into light and deep using a mean Richmond Agitation–Sedation Scale value within the first 48 hours. Propensity score matching was used to balance covariables; the outcomes were compared between the two groups. Results: Overall, 631 patients (418 [66.2%] and 213 [33.8%] in the deep and light sedation groups, respectively) were included. Mortality rates were 14.1% and 8.4% in the deep and light sedation groups (P = 0.039), respectively. Kaplan-Meier estimates showed that time to extubation (P < 0.001), ICU length of stay (P = 0.005), and death P = 0.041) differed between the groups. After adjusting for confounders, early deep sedation was only associated with delayed time to extubation (hazard ratio [HR], 0.66; 95% confidence inter val [CI], 0.55– 0.80; P < 0.001). In the matched cohort, deep sedation remained significantly associated with delayed time to extubation (HR, 0.68; 95% 0.56–0.83; P < 0.001) but was not associated with ICU length of stay (HR, 0.94; 95% CI, 0.79–1.13; P = 0.500) and in-hospital mortality (HR, 1.19; 95% CI, 0.65–2.17; P = 0.582). Conclusion In many Korean ICUs, early deep sedation was highly prevalent in mechanically ventilated patients and was associated with delayed extubation, but not prolonged ICU stay or in-hospital death.

Background and Objectives: Tinnitus, although being a common chronic disease, can be an intractable disease that causes depression and insomnia. This study aimed to analyze the results of the Tinnitus Handicap Inventory (THI), Beck Depression Inventory (BDI), and Pittsburgh Sleep Quality Index (PSQI) questionnaire surveys before and after clonazepam therapy. In addition, we analyzed the association of three pre-treatment questionnaires and evaluated whether pre-treatment factors could predict the post-treatment THI index.Subjects and Method Patients were selected from those who visited a tertiary hospital from 2019 to 2021 for the treatment of chronic tinnitus they had for more than 3 months and who were over 20 years old. Patients were excluded from the study if they were diagnosed with acute sudden hearing loss, Meniere’s disease, brain/internal auditory canal tumors, or muscular/vascular tinnitus. The questionnaire surveys of THI, BDI, PSQI were conducted before and after 3 months of clonazepam therapy (Rivotril [Roche Inc.] 0.25 or 0.5 mg). Questionnaire scores were compared using the paired t-test. Multiple regression analysis was used to determine the relationships among the three questionnaires. Results: A total of 76 patients (38 males and 38 females) with the mean age of 57.2±9.01 years was analyzed. The average hearing threshold was 30.4±20.67 dB HL on the right and 31.7±17.06 dB HL on the left. The pre-treatment THI, BDI, and PSQI scores were 44.3±23.4, 7.96±2.36, and 6.85±4.68, respectively. The relationships between the THI and BDI and the THI and PSQI were significant (p=0.0027 and p<0.0001, respectively). The pre-THI score showed no significant association with age, sex, or hearing threshold (p=0.91, 0.85, and 0.23, respectively). The post-treatment THI score was 33.6±17.1, which was significantly lower than the pre-THI scores (p<0.0001). Post-BDI and post-PSQI were 7.38±2.25 and 4.04±3.20, respectively. Post-PSQI also significantly decreased compared with pre-PSQI (p=0.0002), but post-BDI did not significantly decrease (p=0.1231). In the THI survey, Question 7 (sleep disturbance) showed decrease the most, followed by Question 25 (unstable mood). The post-treatment THI could be predicted by using the formula, 0.7673+0.6947×pre-THI+0.3572×pre-PSQI. Conclusion The appropriate/optional use of clonazepam at low doses (0.25-0.5 mg) can significantly improve chronic tinnitus and sleep quality. Tinnitus was significantly associated with the scores of THI, BDI, PSQI and the usage of Clonazepam significantly reduced the THI and PSQI scores. However, clonazepam did not affect the BDI score.