The Impact and Implications of the Flexner Report on Medical Education in Korea.

The recent debate surrounding the expansion of enrollment in Korean medical schools has reignited interest in the Flexner Report, published in the United States in 1910. Historically, medical education in the United States transitioned from small proprietary schools to university-affiliated institutions, emphasizing basic science and clinical experience. The Flexner Report advocated for scientific medicine and led to significant reforms in medical education, including standardization of curricula and strengthened admission requirements. The influence of this report extended to Korean medical education, shaping its curriculum, accreditation system, and emphasis on academic excellence. The expansion of medical school enrollment has led to a crucial dilemma. Should we prioritize the training of physicians who provide practical medical services or continue to emphasize academic medicine as we do now? There has been insufficient discussion of the individualized curricula, necessary investments, and societal efforts to accommodate these changes. It is imperative to move beyond mere enrollment expansion debates and collectively determine the future trajectory of Korean medical education, devising actionable plans to achieve overarching goals.

Subtyping of Performance Trajectory During Medical School, Medical Internship, and the First Year of Residency in Training Physicians: A Longitudinal Cohort Study.

BACKGROUND: Developmental trajectories of clinical skills in training physicians vary among tasks and show interindividual differences. This study examined the predictors of medical internship performance and residency entrance and found subtypes of performance trajectory in training physicians. METHODS: This retrospective cohort study involved 888 training physicians who completed a medical internship between 2015 and 2019. After the internship, 627 physicians applied for residency training between 2016 and 2020. Finally, 160 of them completed their first-year residency in internal medicine, surgery, pediatrics, and psychiatry departments between 2016 and 2020. Pearson's correlation coefficients of internship performance and first year-residency performance (n = 160) were calculated. Latent profile analysis identified performance trajectory subtypes according to medical school grade point average (GPA), internship performance, English proficiency, and residency selection procedures. Multivariate logistic regression models of residency acceptance (n = 627) and performance in the top 30%/lower 10% in the first year of residency were also constructed. RESULTS: Medical internship performance showed a significant positive correlation with the medical school GPA (r = 0.194) and the written score for the medical licensing examination (r = 0.125). Higher scores in the interview (adjusted odds ratio [aOR], 2.57) and written examination (aOR, 1.45) of residency selection procedures and higher medical internship performance (aOR, 1.19) were associated with a higher chance of residency acceptance. The latent profile analyses identified three training physician subgroups: average performance, consistently high performance (top 30%), and adaptation to changes (lowest 10%). Higher scores in the interview for residency selection (aOR, 1.35) and lower scores for medical internship performance (aOR, 0.79) were associated with a higher chance of performing in the top 30% or lowest 10% in the first year of residency, respectively. CONCLUSION: Performance in the interview and medical internship predicted being among the top 30% and lowest 10% of performers in the first year of residency training, respectively. Individualized educational programs to enhance the prospect of trainees becoming high-functioning physicians are needed.

Impact of a game-based interprofessional education program on medical students' perceptions: a text network analysis using essays.

BACKGROUND: The increasing complexity of the healthcare environment and the necessity of multidisciplinary teamwork have highlighted the importance of interprofessional education (IPE). IPE aims to enhance the quality of patient care through collaborative education involving various healthcare professionals, such as doctors, nurses, and pharmacists. This study sought to analyze how game-based IPE activities influence students' perceptions and reflective thinking. It also aimed to identify the shifts in perception and effectiveness caused by this educational approach. METHODS: The study is based on a game-based IPE program conducted at University A, involving medical and nursing students in structured learning and team-based activities. Data were collected using essays written by the students after they had participated in IPE activities. Text network analysis was conducted by extracting key terms, performing centrality analysis, and visualizing topic modeling to identify changes in students' perceptions and reflective thinking. RESULTS: Keywords such as "patient," "thought," "group," "doctor," "nurse," and "communication" played a crucial role in the network, indicating that students prioritized enhancing their communication and problem-solving skills within the educational environment. The topic modeling results identified three main topics, each demonstrating the positive influence of game-based collaborative activities, interprofessional perspectives, and interdisciplinary educational experiences on students. Topic 3 (interdisciplinary educational experience) acted as a significant mediator connecting Topic 1 (game-based collaborative activity experience) and Topic 2 (interprofessional perspectives). CONCLUSION: This study demonstrates that game-based IPE activities are an effective educational approach for enhancing students' team building skills, particularly communication and interprofessional perspectives. Based on these findings, future IPE programs should focus on creating collaborative learning environments, strengthening communication skills, and promoting interdisciplinary education. The findings provide essential insights for educational designers and medical educators to enhance the effectiveness of IPE programs. Future research should assess the long-term impacts of game-based IPE on clinical practice, patient outcomes, and participants' professional development.

Needs Assessment for the Development of Training Curricula for Internal Medicine Residents.

BACKGROUND: Patient-centered outcomes can be achieved when common core and specialist competencies are achieved in a balanced manner. This study was conducted to assess the need to fill the gap between the defined competencies and learners' achievement, in order to improve the internal medicine (IM) training education curriculum for promoting patient-centered outcomes. METHODS: A cross-sectional online survey was conducted. The participants were 202 IM specialists who obtained board certification in 2020-2021. We developed a questionnaire to investigate the self-evaluation of common core competencies and achievement level of IM essential competencies. For analysis, frequency tests, paired t-test, Borich priority formula, and χ² were performed. RESULTS: In common core competencies, IM specialists recognized that their achievement levels in all competency categories were lower than their importance level (P < 0.001), and the highest educational demands were related to self-management. They assessed their five essential procedure skill levels as novice or advanced beginner status. The achievement level for the essential symptoms and signs that IM specialists should be able to manage was predominantly competent level. However, on average, 34.9% answered that they had never assessed during training for essential skills, and 29.7% answered the same for essential symptoms and signs. CONCLUSION: We identified the priorities of core competencies, the level of achievement in essential procedures and patient care with essential symptoms and signs for IM training, and the related educational methods and assessment status. This study is expected to be used as basic data for developing and revising IM training educational curriculum.

Development and Evaluation of an Inter-professional Education Course at a Medical School in Korea.

BACKGROUND: Interprofessional collaborative practice (IPCP) is emphasized in medical care for patient safety. As patient care is provided by teams, interprofessional competence is required to ensure the quality and safety of care and should be taught as early as possible. In this study, we introduced a 2-week interprofessional education (IPE) curriculum and attempted to describe and evaluate its effectiveness among medical students. METHODS: We developed a 2-week IPE course and gave it to third- or fourth-year medical students (n = 166) from 2018 to 2019. The curriculum was composed of interactive lectures, discussions, small-group discussions, and simulation and was given to diverse medical students. Students were asked to report their satisfaction with the IPE program, write a reflection paper, and complete readiness for interprofessional learning scale (RIPLS) questionnaires before, immediately after, and 4 months after the curriculum. We also obtained 360° evaluations of the students by other health professionals 1 year after the training. RESULTS: The IPE program changed students' attitudes about interprofessional learning, from less favorable to more favorable. The 360° evaluation by nurses revealed that students became more favored as teammates (overall satisfaction with them as teammates increased from 3.1/5 to 3.4/5) compared to medical interns before IPE training, and complaints from nurses about medical interns were significantly less frequent 1 year after the training. CONCLUSION: The IPE program was effective in preparing medical students for team based collaborative practice even though it was short and exposed once in the curriculum. Further extension to other medical schools is recommended.

Erratum: Correction of Text and Table in the Article "Establishing a Patient-centered Longitudinal Integrated Clerkship: Early Results from a Single Institution".

This corrects the article on p. e419 in vol. 35, PMID: 33372421.

Establishing a Patient-centered Longitudinal Integrated Clerkship: Early Results from a Single Institution.

BACKGROUND: Longitudinal integrated clerkships (LICs) have been adopted by medical schools to overcome the limitations of traditional block clerkship rotations and to promote continuity of care. In 2018, Seoul National University College of Medicine introduced a patient-centered LIC program as part of a new curriculum in parallel with traditional block rotation clerkships. The purpose of this study was to present the patient-centered LIC program and to investigate its educational effects. METHODS: In 2018 and 2019, a total of 298 third-year medical students participated in the LIC program. We divided the students into groups of eight, which were organized into corresponding discussion classes. Throughout the academic year, students followed up patients by interviewing them at the hospital or reviewing their electric medical records. Discussion classes on set topics were held seven times per year with facilitators and clinical faculites. Students completed a course evaluation questionnaire at the end of the academic year. The questionnaire included 22 items measured on a 5-point scale and two open-ended questions asking about the benefits and limitations of the program. The items covered three domains: student experience, satisfaction, and self-assessment. Final reflective essays were collected as both student assessments and data for qualitative analysis. RESULTS: During the study period, the overall experience of the students improved. We increased the number of faculty members and patients and decreased the number of students in each discussion class. We also provided additional feedback through an e-portfolio. Students' satisfaction changed positively. Compared to the rotational clerkship, students answered that the LIC provided additional help in learning the two core competencies. During the first 2 years of the program, the percentage of students who answered that the program was more helpful than the rotational clerkship increased from 23.7% to 46.4% for continuity of care (P < 0.001), and from 20.5% to 50.7% for patient-centered care (P < 0.001). CONCLUSION: Our patient-centered LIC, in parallel with traditional block rotation clerkships, had a positive effect on students' experience of continuity of care and patient-centered care.

Implementing Competency-Based Medical Education in Internal Medicine Residency Training Program: the Process and Impact on Residents' Satisfaction.

BACKGROUND: Graduate medical education is shifting from the traditional apprenticeship model to a competency-driven model. Here we describe the design and implementation of competency-based medical education (CBME) in an internal medicine residency program, and report satisfaction survey results. METHODS: We redesigned the residency curriculum as CBME to be resident-centred, systematic, focused on general internal medicine, to provide experience in various care setting, and work-based assessment. In the second year of this CBME transition, we surveyed residents' overall satisfaction using 5-point Likert scale. Feedback on their training program was also analysed. RESULTS: The overall satisfaction score was 3.24 and thirteen residents (61.9%) answered that the preceptor's practical training in an educational atmosphere and improvement through training were the merits of the training program. However, residents complained about the working condition such as work overload. CONCLUSION: With the CBME implementation, most residents expressed satisfaction with the hospital's educational environment but they suffered from overwork. Further efforts to improve the educational program and environment are warranted.

Deliberate Practice as an Effective Remediation Strategy for Underperforming Medical Students Focused on Clinical Skills: a Prospective Longitudinal Study.

BACKGROUND: It is critical to develop remedial education for underperforming medical students, but little is known about how to create an effective remediation program. Deliberate practice (DP) is a structured and reflective activity that is designed to optimize performance. Here we applied the concept of DP to create remedial education to improve the clinical practices of medical students. We also analyzed the effectiveness of the remediation program. METHODS: Based on the expert performance approach of DP, we designed a 4-week remedial program for clinical performance that included feedback and reflection. There were 74 student participants in this program from 2014 to 2017. Their clinical performance was re-evaluated after completion, and changes in their clinical performance scores were analyzed. RESULTS: Students who completed the remediation program showed significant improvements in clinical performance scores (P < 0.001). Most students found the program to be instructive and helpful for improving their clinical performance. They reported that role play with peers was the most helpful for improving their skills. CONCLUSION: The DP-based remediation program improved the clinical performance of failing medical students. This remediation program should continue to be offered to underperforming students to ensure that medical school graduates are competent.

Improving disclosure of medical error through educational program as a first step toward patient safety.

BACKGROUND: Although physicians believe that medical errors should be disclosed to patients and their families, they often hesitate to do so. In this study, we assessed the effectiveness of an education program for medical error disclosure. METHODS: In 2015, six medical interns and 79 fourth-year medical students participated in this study. The education program included practice of error disclosure using a standardized patient scenario, feedback, and short didactic sessions. Participant performance was evaluated with a previously developed rating scale that measures error disclosure performance on five specific component skills. Following education program, we surveyed participant perceptions of medical error disclosure with varying severity of error outcome and their satisfaction with the education program using a 5-point Likert scale. We also surveyed the change of attitude or confidence of participants after education program. RESULTS: The performance score was not significantly different between medical interns and medical students (p = 0.840). Following the education program, 65% of participants said that they had become more confident in coping with medical errors, and most participants (79.7%) were satisfied with the education program. They also indicated that they felt a greater duty to disclose medical errors and deliver an apology when the medical error outcome is more severe. CONCLUSIONS: An education program for disclosing medical errors was helpful in improving confidence in medical error disclosure. Extending the program to more diverse scenarios and a more diverse group of physicians is needed.

Could clinical experience during clerkship enhance students' clinical performance?

BACKGROUND: Medical students learn and practice various clinical skills during clinical clerkship. Patient encounters are important for developing clinical thinking, communication skills, and professional attitude. We investigated whether the amount of clinical experience during clerkship correlated with students' clinical competency and students' perception of effectiveness of their clerkship on it. METHODS: Fourth year medical students undertook the Objective Structured Clinical Examinations (OSCE) in August 2012. Students provided the number of patients for whom they took medical histories or performed physical examinations during clerkship and provided feedback as to whether or not the clinical clerkship was helpful in preparing OSCE. The correlation between the OSCE score and number of patients was analyzed. RESULTS: One hundred thirty students completed the questionnaire (86.6%). OSCE scores correlated with the total number of patients encountered for physical examinations (correlation coefficient, 0.274; p = 0.0105). Cumulative 3-year GPAs were positively correlated with OSCE scores (correlation coefficient, 0.330; p = 0.0001). Most (92.3%) answered that their clinical clerkship was helpful in preparing them for the OSCE; however, only 20% felt that their clinical clerkship was most helpful. Others felt that role playing (38.46%) or the guide book (33.84%) was most helpful. CONCLUSIONS: The amount of clinical experience during the students' clerkship had a small but positive relationship with students' clinical performance. Further research to elucidate the influence of clinical experience on clinical competency is needed.

Guggulsterone attenuates activation and survival of hepatic stellate cell by inhibiting nuclear factor kappa B activation and inducing apoptosis.

BACKGROUND AND AIM: Liver fibrosis is associated with the deposition of the extracellular matrix, and hepatic stellate cells (HSCs) are the major source of these matrix proteins. Guggulsterone has recently been shown to induce apoptosis in several cell lines. Thus, the aim of this study was to evaluate whether guggulsterone has antifibrotic activities by reducing the activation and survival of HSCs. METHODS: Apoptotic and fibrosis-related signaling pathways and nuclear factor kappa B (NF-κB) activity were explored in LX-2 cells, an immortalized human HSC line, and in a mice model of liver fibrosis. RESULTS: Guggulsterone suppressed LX-2 cell growth in a dose- and activation-dependent manner. This growth suppression was due to the induction of HSC apoptosis, which was mediated by the activation of c-Jun N-terminal kinase and mitochondrial apoptotic signaling. Additionally, guggulsterone regulated phosphorylation of Akt and adenosine monophosphate-activated protein kinase, which were subsequently proven responsible for the guggulsterone-induced HSC growth suppression. Guggulsterone inhibited NF-κB activation in LX-2 cells, which is one of the major mediators in HSC activation. Indeed, guggulsterone decreased collagen α1 synthesis and α-smooth muscle actin expression in these cells. Compared with the control mice or mice treated with a low dose of guggulsterone, high dose of guggulsterone significantly decreased the extent of collagen deposition and the percentage of activated HSCs undergoing apoptosis. CONCLUSIONS: These results demonstrate that guggulsterone suppressed HSC activation and survival by inhibiting NF-κB activation and inducing apoptosis. Therefore, guggulsterone may be useful as an antifibrotic agent in chronic liver diseases.

Effect of enhanced analytic reasoning on diagnostic accuracy: a randomized controlled study.

BACKGROUND: Diagnostic error can be caused by several types of cognitive bias, which may be reversed by enhancing analytic reasoning. AIMS: To evaluate whether enhancing analytic reasoning can increase diagnostic accuracy in objective structured clinical examination (OSCE) in medical students. METHODS: All fourth-year medical students, randomly assigned to the analytic reasoning or control groups, undertook the OSCE with four cases using standardized patients. The analytic reasoning group was requested to list differential diagnoses and findings compatible or not compatible with each diagnosis prior to providing a diagnosis, while the control group provided a diagnosis without these processes. Mean diagnostic accuracy scores (perfect score, 4.0) from four cases of OSCE were compared between the two groups. RESULTS: One hundred forty-five students were randomly assigned to the analytic reasoning group (n = 65) or the control group (n = 80). The baseline characteristics, including grade point average and the scores from each patient encounter, were comparable between groups. Mean diagnostic accuracy scores were significantly higher in the analytic reasoning group than in the control group (3.40 ± 0.66 versus 3.05 ± 0.98; p = 0.011). CONCLUSION: Enhancement of analytic reasoning may improve diagnostic accuracy in novice doctors.

Associations among the workplace violence, burnout, depressive symptoms, suicidality, and turnover intention in training physicians: a network analysis of nationwide survey.

Depression and anxiety are the most common mental disorders among physicians, who have a greater risk of suicide than those in other professional occupations. Relationships among a demanding workload, workplace violence, burnout, and intention to turnover have also been reported. The current study examined the principal components and propagating patterns of mental health and working environment interactions in training physicians. A total of 1981 training physicians completed online self-report questionnaires during September-October (midpoint of the training year) 2020. Regularized partial correlations in a mixed graphical model (MGM) and joint probability distributions (directed acyclic graph; DAG) were estimated for four subtypes of workplace violence (verbal abuse/physical violence perpetrated by clients/hospital staff), three burnout subdomains (Maslach Burnout Inventory), thoughts about quitting, and nine depressive symptoms, including suicidality, comprising the DSM-5 diagnostic criteria for major depressive disorder (assessed using the Patient Health Questionnaire-9). Thoughts of death/self-harm showed directional dependencies on the joint probability distributions of psychomotor agitation/retardation, concentration difficulty, self-reproach, and sadness in the DAG. In the MGM, a partial correlation with psychomotor agitation/retardation (r = 0.196) accounted for 56.5% of the variance in thoughts of death/self-harm. Partial correlations with concentration difficulties (r = 0.294), self-reproach (r = 0.257), changes in appetite (r = 0.184), and worker-on-worker physical violence (r = 0.240) in the MGM accounted for 54.4% of the variance in psychomotor agitation/retardation. Thoughts about quitting were partially correlated with and dependent upon the joint probability distributions of emotional exhaustion (r = 0.222), fatigue (r = 0.142), anhedonia (r = 0.178), and sadness (r = 0.237). In contrast, worker-on-worker (r = 0.417) and client-on-physician (r = 0.167) verbal abuse had regularized partial correlations with directional dependencies on thoughts about quitting. Organization-level interventions aiming to reduce the worker-on-worker violence and individual-level approaches of clinical screening program and psychiatric counseling clinic are required. Follow-up studies to verify the effectiveness of these interventions for training physicians are needed.

Prognostic implications of tumor vascularity and its relationship to cytokeratin 19 expression in patients with hepatocellular carcinoma.

OBJECTIVE: Although hepatocellular carcinoma (HCC) demonstrates characteristic hypervascularity, some HCCs have a hypovascular pattern on computed tomography (CT). Cytokeratin 19 (CK19) is a marker for the biliary phenotype reflecting a poor prognosis. We assessed the prognostic implications of tumor vascularity and its association with CK19 expression in HCC. METHODS: Patients that underwent surgical resection for HCC were included. Tumor vascularity was evaluated according to the arterial enhancement patterns on CT scans and CK19 expression was evaluated by using tissue microarray methods. RESULTS: One hundred and forty patients were included. Their median follow-up duration was 55.0 months, and 92 (65.7%) patients had tumor recurrence. Forty-five patients (30.6%) had hypovascular HCC at the time of diagnosis, and they showed a significantly higher CK19 expression rate (32.5% vs. 8.2%, P = 0.001) and earlier recurrence rate within 6 months (hazard ratio (HR), 2.301; P = 0.025) compared to the patients with hypervascular HCCs. Hypovascularity (HR, 1.694; P = 0.045) was an independent risk factor for short overall survival. CONCLUSIONS: Hypovascular HCCs were associated with early recurrence and short overall survival, and CK19 was more frequently expressed in hypovascular HCC than in hypervascular tumors. Therefore, tumor vascularity on CT images might be utilized in determining the prognosis of patients with HCCs.

How to enhance students' learning in a patient-centered longitudinal integrated clerkship: factors associated with students' learning experiences.

PURPOSE: Longitudinal integrated clerkships (LICs) have been introduced in medical schools, as learning relationships with clinical faculty or peers are important components of medical education. The purpose of this study was to investigate the characteristics of student-faculty and student-student interactions in the LIC and to identify other factors related to whether students understood and acquired the program's main outcomes. METHODS: The study was conducted among the 149 third-year students who participated in the LIC in 2019. We divided the students into groups of eight. These groups were organized into corresponding discussion classes, during which students had discussions with clinical faculty members and peers and received feedback. Clinical faculty members and students were matched through an e-portfolio, where records were approved and feedback was given. A course evaluation questionnaire was completed and analysed. RESULTS: A total of 144 valid questionnaires were returned. Logistic regression analysis showed that relevant feedback in discussion classes (adjusted odds ratio [AOR], 5.071; p<0.001), frequency of e-portfolio feedback (AOR, 1.813; p=0.012), and motivation by e-portfolio feedback (AOR, 1.790; p=0.026) predicted a greater likelihood of understanding the continuity of the patient's medical experience. Relevant feedback from faculty members in discussion classes (AOR, 3.455; p<0.001) and frequency of e-portfolio feedback (AOR, 2.232; p<0.001) also predicted a greater likelihood of understanding the concept of patient-centered care. CONCLUSION: Student-faculty interactions, including relevant feedback in discusstion classes, frequency of e-portfolio feedback, and motivation by e-portfolio feedback were found to be important factors in the LIC program.

Serum HBsAg levels during peginterferon α-2a treatment with or without thymosin α-1 in HBeAg-positive chronic hepatitis B patients.

The importance of serum hepatitis B surface antigen (HBsAg) level as a surrogate marker for viral load and a predictor of treatment response remains unclear. The aim of this study was to investigate whether serum HBsAg correlates with serum hepatitis B virus (HBV) DNA during peginterferon (PEG-IFN) α-2a treatment (with or without thymosin α-1) in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients and whether it can predict treatment response. Sera from 37 HBeAg-positive chronic hepatitis B patients receiving 48-weeks PEG-IFN α-2a with (n = 20) or without (n = 17) an initial 12-weeks thymosin α-1 were obtained at baseline and at weeks 12, 24, 36, 48 (end of treatment), 56, 72, 84, and 96 (end of follow-up). Taqman HBV DNA tests (Roche) and Architect HBsAg QT (Abbott) were performed. There was a moderate correlation between the HBsAg and HBV DNA levels (r = 0.452, P < 0.001). Median HBsAg levels at baseline and at week 96 were 6,218 IU/ml and 4,038 IU/ml, respectively. The mean HBV DNA and alanine aminotransferase (ALT) levels were 7.48 log(10) IU/ml and 173 IU/L at baseline and 5.37 log(10) IU/ml and 102 IU/L at week 96, respectively. A decrease to <60% of baseline levels of HBsAg at week 12 was identified as an independent predictive factor for HBeAg seroconversion (OR = 45.7, P < 0.05) at week 96. Serum HBsAg levels may be helpful for predicting the response to PEG-IFN therapy in HBeAg-positive chronic hepatitis B patients.

Inhibition of hypoxia-inducible carbonic anhydrase-IX enhances hexokinase II inhibitor-induced hepatocellular carcinoma cell apoptosis.

AIM: The hypoxic condition within large or infiltrative hypovascular tumors produces intracellular acidification, which could activate many signaling pathways and augment cancer cell growth and invasion. Carbonic anhydrase-IX (CA-IX) is an enzyme lowering pH. This study is to examine whether hypoxia induces CA-IX in hepatocellular carcinoma (HCC) cells, and to evaluate its clinical implication in HCC patients. METHODS: Human HCC cell lines (Huh-7 and HepG2 cells) were used, and cell growth was assessed using MTS assay. CA-IX expression and apoptotic/kinase signaling were evaluated using immunoblotting. The cells were transfected with CA-IX-specific siRNA, or treated with its inhibitor 4-(2-aminoethyl) benzenesulfonamide (CAI#1), and/or the hexokinase II inhibitor, 3-bromopyruvate (3-BP). A clinic pathological analysis of 69 patients who underwent an HCC resection was performed using a tissue array. RESULTS: Incubation of HCC cells under hypoxia (1% O2, 5% CO2, 94% N2) for 36 h significantly increased CA-IX expression level. CAI#1 (400 µmol/L) or CA-IX siRNA (100 µmol/L) did not influence HCC cell growth and induce apoptosis. However, CAI#1 or CA-IX siRNA at these concentrations enhanced the apoptosis induced by 3-BP (100 µmol/L). This enhancement was attributed to increased ER stress and JNK activation, as compared with 3-BP alone. Furthermore, a clinic pathological analysis of 69 HCC patients revealed that tumor CA-IX intensity was inversely related to E-cadherin intensity. CONCLUSION: Inhibition of hypoxia-induced CA-IX enhances hexokinase II inhibitor-induced HCC apoptosis. Furthermore, CA-IX expression profiles may have prognostic implications in HCC patients. Thus, the inhibition of CA-IX, in combination with a hexokinase II inhibitor, may be therapeutically useful in patients with HCCs that are aggressively growing in a hypoxic environment.

Impact of COVID-19 on Lifestyle, Personal Attitudes, and Mental Health Among Korean Medical Students: Network Analysis of Associated Patterns.

The current COVID-19 pandemic have affected our daily lifestyle, pressed us with fear of infection, and thereby changed life satisfaction and mental health. The current study investigated influencing cascade of changes during the COVID-19 among the lifestyle, personal attitudes, and life (dis)satisfaction for medical students, using network-based approaches. This cross-sectional survey used self-reports of 454 medical students during June and July of 2020. Depressive mood, anxiety, and intention to drop out of school were observed in 11.9, 18.5, and 38.3% of medical students, respectively. Directed acyclic graph that estimated directional propagation of the COVID-19 in medical students' daily lives initiated from the perception of unexpected event, propagated to nervous and stressed feeling, trouble relaxing, feeling like a failure, and were followed by trouble concentrating, feeling loss of control for situation, and fear of infecting colleagues. These six features were also principal mediators within the intra-individual covariance networks comprised of changed lifestyle, personal attitude, and mental health at COVID-19 pandemic. Psychosocial supports targeting nervousness, trouble relaxing and concentrating, fear of spreading infection to colleagues, feelings of a failure or loss of situational control are required for better mental health of medical students during the COVID-19 pandemic.

Synergistic antifibrotic efficacy of statin and protein kinase C inhibitor in hepatic fibrosis.

Statin has antifibrotic efficacy in human fibrosing diseases, such as pulmonary and renal fibrosis, and is therefore implicated in hepatic fibrosis. However, statin can also activate protein kinase C (PKC), which augments hepatic fibrogenesis and is thereby likely to reduce the antifibrotic efficacy of statin. This study was designed to explore the hypothesis that simultaneous treatment with statin and PKC inhibitor may synergistically enhance antifibrotic efficacy in hepatic fibrosis. Hepatic fibrosis models were established in BALB/c mice by intraperitoneal injection of carbon tetrachloride or thioacetamide for 6 wk. Pravastatin and enzastaurin (PKC inhibitor) were administered by gavage for 5 wk. Cellular apoptosis was explored using 4',6-diamidino-2-phenylindole or terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end-labeling (TUNEL) staining and immunoblot analysis. Hepatic fibrosis and hepatic stellate cell (HSC) activation were assessed by morphometric analysis of histological findings and immunohistochemistry for alpha-smooth muscle actin. In vitro, the addition of PKC inhibitor significantly increased statin-induced LX-2 cell apoptosis by enhancing the activation of mitochondrial apoptotic signals. TUNEL-positive HSCs were significantly increased in mice treated with statin + PKC inhibitor compared with those in control or single compound-treated mice. The percentage of area occupied by activated HSCs and the extent of collagen deposition were significantly decreased in mice treated with statin + PKC inhibitor compared with those in control or statin-treated mice. In conclusion, simultaneous treatment with statin and PKC inhibitor synergistically enhanced the antifibrotic efficacy in both in vitro and in vivo models of hepatic fibrosis and may therefore have therapeutic implication for reducing hepatic fibrosis.