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Cancer cell heterogeneity is a serious problem in the control of tumor progression because it can cause chemoresistance and metastasis. Heterogeneity can be generated by various mechanisms, including genetic evolution of cancer cells, cancer stem cells (CSCs), and niche heterogeneity. Because the genetic heterogeneity of CSCs has been poorly characterized, the genetic mutation status of CSCs was examined using Exome-Seq and RNA-Seq data of liver cancer.Here we show that different surface markers for liver cancer stem cells (LCSCs) showed a unique propensity for genetic mutations. Cluster of differentiation 133 (CD133)-positive cells showed frequent mutations in the IRF2, BAP1, and ERBB3 genes. However, leucine-rich repeat-containing G protein-coupled receptor 5-positive cells showed frequent mutations in the CTNNB1, RELN, and ROBO1 genes. In addition, some genetic mutations were frequently observed irrespective of the surface markers for LCSCs. BAP1 mutations was frequently observed in CD133-, CD24-, CD13-, CD90-, epithelial cell adhesion molecule-, or keratin 19-positive LCSCs. ASXL2, ERBB3, IRF2, TLX3, CPS1, and NFATC2 mutations were observed in more than three types of LCSCs, suggesting that common mechanisms for the development of these LCSCs. The present study provides genetic heterogeneity depending on the surface markers for LCSCs. The genetic heterogeneity of LCSCs should be considered in the development of LCSC-targeting therapeutics.
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Objective@#This study investigated whether sleep and stress mutually interact to induce changes in white matter integrity. @*Methods@#Diffusion tensor imaging (DTI) was conducted on 36 participants (male=22, female=14; mean age=38.33±12.78 years). Participants were divided into three groups depending on their sleep quality and stress levels: poor sleepers with stress, poor sleepers without stress, and good sleepers. Sleep quality and stress level were evaluated using the Pittsburgh Sleep Quality Index and the Life Experiences Survey, respectively. Fractional anisotropy (FA) values were calculated employing DTI tractography. @*Results@#After controlling for age and sex, poor sleepers with stress exhibited a lower FA of the left inferior cerebellar peduncle (ICP) than did poor sleepers without stress (t=2.81, p=0.02). Poor sleepers without stress showed a higher FA of the right middle longitudinal fasciculus (MdLF) than did good sleepers (t=3.35, p=0.006). @*Conclusion@#The current study reports the effects of sleep, stress, and their interaction on the white matter integrities of the ICP and MdLF. ICP change seems to be associated with sleep disturbances related to stress, while MdLF change would be associated with sleep disturbances unrelated to stress.
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Objectives@#Suicide is the major public mental health concerns all over the world. The comparison of suicide attempters and suicide completers could be the fundamental evidence for the suicide prevention. The aim of this study is to explore the differences between suicide attempters and suicide completers in terms of the stressors, suicide methods, and psychiatric diagnosis. @*Methods@#Two types of secondary data were collected for the analyses. Data of the suicide attempters (n = 680) were gathered by intensive reviewing the medical records of Samsung Medical Center, Seoul, Republic of Korea. Data of suicide completers (n = 11,722) were collected by the psychological autopsy data which were gathered by Korean Foundation for Suicide Prevention. Suicidal methods, psychiatric disorders and stressors before suicidal attempt were compared between suicide attempter and completers. @*Results@#Suicide completers were older and male predominant compared to suicidal attempt. Hanging or gas intoxication were more commonly used in the suicide completion, while wrist cutting or drug intoxication were more common in suicide attempters. All types of stressors were found to be high in suicide completers than suicide attempters. However, the proportion of economic and physical stress were greater in suicide completers, while the proportion of family stress were greater in suicide attempters. According to the recorded diagnoses, the rates of depressive disorders, sleep-wake disorders, substance-related disorders were higher in suicide completers, while the rates of anxiety disorders and trauma- and stressor-related disorders, bipolar and related disorders and somatic symptom disorders were higher in suicide attempters. However, after controlling the gender and age, there were no significant differences in diagnosis between suicide attempters and suicide completers. @*Conclusion@#These findings implicate that suicide attempters and completers differed in suicide methods and type of stress. The results suggests that economic stressors, physical illness might raise the risk of suicide completion.
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The purpose of this study was to redesign a problem-based learning (PBL) curriculum and compare the differences between the previous and redesigned PBL based on the results of course satisfaction and student assessments. The PBL was redesigned using curriculum design guidelines (including revisions of curriculum objectives, learning components, learning environments, and assessment methods) that were developed based on previous studies and evaluation results. A comparative study was employed using course satisfaction surveys from the previous and redesigned curricula, and a total of 45 students participated. We also compared student assessment results from concept mapping, learning issue reports, modified essay questions, and reflection journals. We identified four key findings. First, we explored the possibility that the redesigned PBL could be implemented by student facilitators without professors as tutors. Second, the redesigned PBL fostered group dynamics that facilitated developing communication skills and collaborative learning through small-group discussions. Third, the new learning elements added in the redesigned PBL made a meaningful contribution to enhancing students’ clinical reasoning based on hypothetico-deductive reasoning. Fourth, concept maps in redesigned PBL contained more complex and various nodes and connections, and the levels of the nodes were more appropriate. The implications of this study can provide meaningful preliminary information for redesigning PBL curricula for medical students to develop their essential competencies through PBL.
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Background and Objectives@#In patients with atrial fibrillation (AF), females taking vitamin K antagonist are at higher risk of stroke or systemic embolism (SSE), bleeding and all-cause death than males. This study investigated the relationship between sex and adverse clinical events in a contemporary AF patient cohort taking anticoagulation. @*Methods@#This prospective multicenter AF registry study comprised 6,067 patients with AF (mean age, 70±9 years; men, 59%) with intermediate to high risk of stroke (CHA 2 DS 2-VAscore ≥1) and receiving oral anticoagulation therapy. Adverse clinical outcomes, including SSE, bleeding, death were evaluated in patients stratified by sex and anticoagulation patterns. @*Results@#Women were older and used more direct oral anticoagulants (85% vs. 78%, p<0.001) than men. During a median (25 the and 75 the percentiles) follow-up of 30 (24, 38) months, the incidence rate and risk of SSE (0.7 in women vs. 0.7 in men per 100 person-years) and major bleeding (0.1 in women vs. 0.1 in men per 100 person-years) were not different between the sexes. However, women had a lower all-cause death rate (0.4 in women vs. 0.6 in men per 100 person-years, hazard ratio: 0.48, 95% confidence interval: 0.25–0.91, p=0.025) than men. @*Conclusions@#In contemporary anticoagulation for AF, SSE and major bleeding risks did not differ between sexes. However, women showed a lower risk of all-cause death rate than men, indicating that the use of oral anticoagulants for treating AF in females does not appear to be a risk factor for adverse clinical events.
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Purpose@#To identify clinical factors associated with the early reduction of corneal sensitivity (CS) in patients with herpes zoster ophthalmicus (HZO). @*Methods@#Total 30 subjects were divided into two groups according to the occurrence of an early reduction of CS (group 1, normal CS; group 2, decreased CS). The demographics, ocular manifestations of HZO, and the ocular surface parameters were compared between two groups. Then, the relative risks of variables were analyzed to expect the early decrease of CS by HZO using logistic regression analysis. @*Results@#Among total 30 subjects, the CS decreased in 10 subjects (3.2 ± 1.4 cm, group 2) and the other 20 subjects revealed normal CS (6.0 ± 0.0 cm, group 1). The age was higher in the group 2 (67.0 ± 16.6 years) than in group 1 (48.0 ± 17.6 years, p = 0.013), but sex and the comorbidity of diabetes mellitus was not difference between groups. The presence of corneal punctate epithelial erosions was a single factor among the ocular manifestations of HZO, which discriminated group 1 (5%) and group 2 (60%, p = 0.002). The ocular surface staining scores (i.e., National Eye Institute scores and Sjögren’s International Collaborative Clinical Alliance ocular surface score) were higher in group 2 (p = 0.001 and p = 0.021, respectively) than in group 1. The existence of corneal punctate epithelial erosions revealed as a sole risk factor for the early reduction of CS (odds ratio = 33.085; p = 0.016). @*Conclusions@#It is necessary to pay attention to the possible occurrence of neurotrophic keratopathy especially in older patients with HZO showing an initial presence of corneal punctate epithelial erosions.
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Liver fibrosis is part of the wound healing process to help the liver recover from the injuries caused by various liver-damaging insults. However, liver fibrosis often progresses to life-threatening cirrhosis and hepatocellular carcinoma. To overcome the limitations of current in vivo liver fibrosis models for studying the pathophysiology of liver fibrosis and establishing effective treatment strategies, we developed a new mouse model of liver fibrosis using polyhexamethylene guanidine phosphate (PHMG-p), a humidifier sterilizer known to induce lung fibrosis in humans. Male C57/BL6 mice were intraperitoneally injected with PHMG-p (0.03% and 0.1%) twice a week for 5 weeks. Subsequently, liver tissues were examined histologically and RNA-sequencing was performed to evaluate the expression of key genes and pathways affected by PHMG-p. PHMG-p injection resulted in body weight loss of ~15% and worsening of physical condition. Necropsy revealed diffuse fibrotic lesions in the liver with no effect on the lungs. Histology, collagen staining, immunohistochemistry for smooth muscle actin and collagen, and polymerase chain reaction analysis of fibrotic genes revealed that PHMG-p induced liver fibrosis in the peri-central, peri-portal, and capsule regions. RNA-sequencing revealed that PHMG-p affected several pathways associated with human liver fibrosis, especially with upregulation of lumican and IRAK3, and downregulation of GSTp1 and GSTp2, which are closely involved in liver fibrosis pathogenesis. Collectively we demonstrated that the PHMG-p-induced liver fibrosis model can be employed to study human liver fibrosis.
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Purpose@#To report a case of refractory recurrent corneal erosion that occurred after Descemet’s stripping automated endothelial keratoplasty (DSAEK) in iridocorneal endothelial syndrome.Case summary: A 62-year-old male patient with iridocorneal endothelial syndrome planned to undergo ultrathin DSAEK. At the surgery, corneal epithelial debridement was performed using a No. 15 blade to enhance the surgical field visibility. Three corneal venting incisions were made before graft insertion in the recipient eye. The corneal epithelium was healed at postoperative 1 week. However, the epithelium detached at 2 weeks postoperatively. The loosened epithelium was peeled off, and a therapeutic bandage contact lens was applied. Thereafter, the corneal epithelial detachment did not improve, despite repeated corneal epithelial debridement, prolonged therapeutic bandage contact lens wear, applications of 5% sodium chloride eyedrops and autoserum eyedrops, and intake of doxycycline, steroids, and valaciclovir. Anterior stromal puncture was performed three times, and the corneal epithelium eventually attached at postoperative 8 weeks. Although recurrent corneal erosion was not observed at postoperative 10 weeks, acute graft rejection occurred but improved with immunosuppressive treatment. The corrected visual acuity was 0.8 after cataract surgery, which was performed at 1 year after DSAEK. @*Conclusions@#Refractory recurrent corneal erosion may occur after DSAEK surgery. In such a case, an aggressive treatment including the repeated anterior stromal puncture technique may be helpful.
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Purpose@#We report a case of adult-onset atypical Stevens-Johnson syndrome (SJS) in which only the oral and ocular mucosae were involved, without skin lesions. Case summary: A 33-year-old man was referred to our institute with recent severe oral mucositis and bilateral conjunctival hyperemia and pseudomembrane formation, which occurred 5 days after taking cold medicine, including a non-steroidal anti-inflammatory drug, acetaminophen and cefaclor, for pharyngitis with fever. At the initial visit, the patient had an epithelial defect of the bulbar and tarsal conjunctiva in both eyes. Conservative treatment using topical eye drops was started, with suspicion of atypical SJS. In addition, HLA-A alleles were typed to assess possible genetic susceptibility to the relevant drugs, and HLA-A*11:01 and HLA-A*31:01 alleles were confirmed. Immunoglobulin (Ig) G against Mycoplasma pneumoniae was positive and IgM was negative at 10 months after the initial onset of disease. One year after the disease onset, autologous serum eye drops, oral and topical steroids, 0.1% cyclosporine eye drops, and antibiotic eye drops were maintained and the corneal and conjunctival erosions were much improved. @*Conclusions@#Although atypical SJS is very rare, it is important to suspect it early by taking a history of any preceding medication or possible concurrent mycoplasma pneumonia, because atypical SJS may affect the oral and ocular mucosae without skin lesions.
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Purpose@#To report a case with bilateral circumscribed posterior keratoconus with different results of refractive error between eyes after cataract surgery. Case summary: A 57-year-old man was referred for decreased vision and suspected keratoconus in both eyes. The corrected visual acuity was 0.04 in the right eye and 0.2 in the left eye. On slit-lamp microscopy and anterior-segment optical coherence tomography (AS-OCT) examination, the excavation of the posterior corneal surface was observed in the central area of the right eye and in the mid-to-inferior area of the left eye. Considering the posterior corneal refractive power measured within the 8-mm zone on AS-OCT, we expected the postoperative hyperopic shift in the refractive error of 2.61 diopters (D) in the right eye and 2.17 D in the left eye. Accordingly, the adjusted predicted refractive error was determined as -0.68 D in the right eye and -1.06 D in the left eye, based on the Barrett Universal II formula. The postoperative values of the spherical equivalent by manifest refraction was -1.0 D in the right eye and -3.0 D in the left eye at 1 month, which was close to the predicted target in the right eye, but myopic by approximately 2.0 D in the left eye, compared to the predicted values. @*Conclusions@#In patients with bilateral circumscribed posterior keratoconus, the location, depth, and area of the excavation of the posterior corneal surface should be considered independently in both eyes to calculate the intraocular lens power more accurately.
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Purpose@#To report a case of conjunctival xanthoma occurring at the plica semilunaris.Case summary: A 39-year-old female with no specific medical history visited our hospital due to a recent incidental detection of a painless mass in the nasal conjunctiva of her right eye. Slit-lamp bio-microscopic examination revealed a yellowish movable oval mass with inner semi-translucency in the temporal area of the plica semilunaris. The vertical length of the mass was approximately 8 mm. It was well-demarcated at its temporal border; however, the nasal border was obscured behind the plica semilunaris. Considering a possible conjunctival reactive lymphoid hyperplasia, topical and systemic steroids as well as oral doxycycline were administrated for 1 week; however, the lesion showed no improvement. An excisional biopsy was performed; pathological diagnosis indicated conjunctival xanthoma. The patient’s blood lipid profile was within the normal range. @*Conclusion@#Conjunctival xanthoma can develop near the plica semilunaris. Because it is difficult to distinguish xanthoma from other diseases including orbital fat prolapse or lymphoproliferative disease, rapid biopsy would be helpful for an early diagnosis.
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Background@#Non-obstetric surgery during pregnancy is associated with adverse obstetric and fetal outcomes. The aim of this study was to investigate the risk of adverse pregnancy outcomes for women who underwent non-obstetric pelvic surgery during pregnancy compared with that of women that did not undergo surgery. @*Methods@#Study data from women who gave birth in Korea were collected from the Korea National Health Insurance claims database between 2006 and 2016. We identified pregnant women who underwent abdominal non-obstetric pelvic surgery by laparoscopy or laparotomy from the database. Pregnancy outcomes including preterm birth, low birth weight (LBW), cesarean section (C/S), gestational hypertension, gestational diabetes, and postpartum hemorrhage were identified. The adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the pregnancy outcomes were estimated by multivariate regression models. @*Results@#Data from 4,439,778 women were collected for this study. From 2006–2016, 9,417 women from the initial cohort underwent non-obstetric pelvic surgery (adnexal mass resection, appendectomy) during pregnancy. Multivariate logistic regression analysis indicated that preterm birth (HR, 2.01; 95% CI, 1.81–2.23), LBW (HR, 1.62; 95% CI, 1.46– 1.79), C/S (HR, 1.13; 95% CI, 1.08–1.18), and gestational hypertension (HR, 1.35; 95% CI, 1.18–1.55) were significantly more frequent in women who underwent non-obstetric surgery during pregnancy compared to pregnant women who did not undergo surgery. When the laparoscopic and laparotomy groups were compared for risk of fetal outcomes, the risk of LBW was significantly decreased in laparoscopic adnexal resection during pregnancy compared to laparotomy (odds ratio, 0.62; 95% CI, 0.40–0.95). @*Conclusion@#Non-obstetric pelvic surgery during pregnancy was associated with a higher risk of preterm birth, LBW, gestational hypertension, placenta previa, placental abruption, and C/S. Although the benefits and safety of laparoscopy during pregnancy appear similar to those of laparotomy in regard to pregnancy outcomes, laparoscopic adnexal mass resection was associated with a lower risk of LBW.
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Purpose@#This study was designed to analyze the risk factors for poor survival after recurrence of hepatocellular carcinoma after liver transplantation. @*Methods@#Patients who underwent liver transplantation for hepatocellular carcinoma during the period of 2007 to 2018 were reviewed and patients who experienced recurrence were included. Multivariable Cox proportional hazard ratios were performed for potential risk factors for survival after recurrence. @*Results@#A total of 151 recipients experienced hepatocellular carcinoma recurrence after liver transplantation. The median of the recurrence-free period was 9.3 months (0.89–97.25 months). The median follow-up after recurrence was 13.4 months (0.59–118.28 months). One-, 3-, and 5-year survival after recurrence were 65.2%, 34.0% and 20.5%, respectively.Multivariable Cox analysis showed that, graft from living donor (hazard ratio [HR], 0.430; 95% confidence interval [CI], 0.210–0.882; P = 0.021), recurrence-free interval of ≥9 months (HR, 0.257; 95% CI, 0.164–0.403; P < 0.001), alphafetoprotein of ≥100 ng/mL at the time of recurrence (HR, 1.689; 95% CI, 1.059–2.695; P = 0.028), and recurrence in bone (HR, 2.304; 95% CI, 1.399–3.794; P = 0.001) and everolimus within 3 months after recurrence (HR, 0.354; 95% CI, 0.141–0.889; P = 0.027) were related to survival after recurrence. @*Conclusion@#Although survival was generally poor after recurrence of hepatocellular carcinoma in liver transplantation recipients, prolonged survival can be achieved in certain patients with better prognostic factors.
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Purpose@#We report a case of adult-onset atypical Stevens-Johnson syndrome (SJS) in which only the oral and ocular mucosae were involved, without skin lesions. Case summary: A 33-year-old man was referred to our institute with recent severe oral mucositis and bilateral conjunctival hyperemia and pseudomembrane formation, which occurred 5 days after taking cold medicine, including a non-steroidal anti-inflammatory drug, acetaminophen and cefaclor, for pharyngitis with fever. At the initial visit, the patient had an epithelial defect of the bulbar and tarsal conjunctiva in both eyes. Conservative treatment using topical eye drops was started, with suspicion of atypical SJS. In addition, HLA-A alleles were typed to assess possible genetic susceptibility to the relevant drugs, and HLA-A*11:01 and HLA-A*31:01 alleles were confirmed. Immunoglobulin (Ig) G against Mycoplasma pneumoniae was positive and IgM was negative at 10 months after the initial onset of disease. One year after the disease onset, autologous serum eye drops, oral and topical steroids, 0.1% cyclosporine eye drops, and antibiotic eye drops were maintained and the corneal and conjunctival erosions were much improved. @*Conclusions@#Although atypical SJS is very rare, it is important to suspect it early by taking a history of any preceding medication or possible concurrent mycoplasma pneumonia, because atypical SJS may affect the oral and ocular mucosae without skin lesions.
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Purpose@#To report a case with bilateral circumscribed posterior keratoconus with different results of refractive error between eyes after cataract surgery. Case summary: A 57-year-old man was referred for decreased vision and suspected keratoconus in both eyes. The corrected visual acuity was 0.04 in the right eye and 0.2 in the left eye. On slit-lamp microscopy and anterior-segment optical coherence tomography (AS-OCT) examination, the excavation of the posterior corneal surface was observed in the central area of the right eye and in the mid-to-inferior area of the left eye. Considering the posterior corneal refractive power measured within the 8-mm zone on AS-OCT, we expected the postoperative hyperopic shift in the refractive error of 2.61 diopters (D) in the right eye and 2.17 D in the left eye. Accordingly, the adjusted predicted refractive error was determined as -0.68 D in the right eye and -1.06 D in the left eye, based on the Barrett Universal II formula. The postoperative values of the spherical equivalent by manifest refraction was -1.0 D in the right eye and -3.0 D in the left eye at 1 month, which was close to the predicted target in the right eye, but myopic by approximately 2.0 D in the left eye, compared to the predicted values. @*Conclusions@#In patients with bilateral circumscribed posterior keratoconus, the location, depth, and area of the excavation of the posterior corneal surface should be considered independently in both eyes to calculate the intraocular lens power more accurately.
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Purpose@#To report a case of conjunctival xanthoma occurring at the plica semilunaris.Case summary: A 39-year-old female with no specific medical history visited our hospital due to a recent incidental detection of a painless mass in the nasal conjunctiva of her right eye. Slit-lamp bio-microscopic examination revealed a yellowish movable oval mass with inner semi-translucency in the temporal area of the plica semilunaris. The vertical length of the mass was approximately 8 mm. It was well-demarcated at its temporal border; however, the nasal border was obscured behind the plica semilunaris. Considering a possible conjunctival reactive lymphoid hyperplasia, topical and systemic steroids as well as oral doxycycline were administrated for 1 week; however, the lesion showed no improvement. An excisional biopsy was performed; pathological diagnosis indicated conjunctival xanthoma. The patient’s blood lipid profile was within the normal range. @*Conclusion@#Conjunctival xanthoma can develop near the plica semilunaris. Because it is difficult to distinguish xanthoma from other diseases including orbital fat prolapse or lymphoproliferative disease, rapid biopsy would be helpful for an early diagnosis.
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Background@#Non-obstetric surgery during pregnancy is associated with adverse obstetric and fetal outcomes. The aim of this study was to investigate the risk of adverse pregnancy outcomes for women who underwent non-obstetric pelvic surgery during pregnancy compared with that of women that did not undergo surgery. @*Methods@#Study data from women who gave birth in Korea were collected from the Korea National Health Insurance claims database between 2006 and 2016. We identified pregnant women who underwent abdominal non-obstetric pelvic surgery by laparoscopy or laparotomy from the database. Pregnancy outcomes including preterm birth, low birth weight (LBW), cesarean section (C/S), gestational hypertension, gestational diabetes, and postpartum hemorrhage were identified. The adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the pregnancy outcomes were estimated by multivariate regression models. @*Results@#Data from 4,439,778 women were collected for this study. From 2006–2016, 9,417 women from the initial cohort underwent non-obstetric pelvic surgery (adnexal mass resection, appendectomy) during pregnancy. Multivariate logistic regression analysis indicated that preterm birth (HR, 2.01; 95% CI, 1.81–2.23), LBW (HR, 1.62; 95% CI, 1.46– 1.79), C/S (HR, 1.13; 95% CI, 1.08–1.18), and gestational hypertension (HR, 1.35; 95% CI, 1.18–1.55) were significantly more frequent in women who underwent non-obstetric surgery during pregnancy compared to pregnant women who did not undergo surgery. When the laparoscopic and laparotomy groups were compared for risk of fetal outcomes, the risk of LBW was significantly decreased in laparoscopic adnexal resection during pregnancy compared to laparotomy (odds ratio, 0.62; 95% CI, 0.40–0.95). @*Conclusion@#Non-obstetric pelvic surgery during pregnancy was associated with a higher risk of preterm birth, LBW, gestational hypertension, placenta previa, placental abruption, and C/S. Although the benefits and safety of laparoscopy during pregnancy appear similar to those of laparotomy in regard to pregnancy outcomes, laparoscopic adnexal mass resection was associated with a lower risk of LBW.
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Purpose@#This study was designed to analyze the risk factors for poor survival after recurrence of hepatocellular carcinoma after liver transplantation. @*Methods@#Patients who underwent liver transplantation for hepatocellular carcinoma during the period of 2007 to 2018 were reviewed and patients who experienced recurrence were included. Multivariable Cox proportional hazard ratios were performed for potential risk factors for survival after recurrence. @*Results@#A total of 151 recipients experienced hepatocellular carcinoma recurrence after liver transplantation. The median of the recurrence-free period was 9.3 months (0.89–97.25 months). The median follow-up after recurrence was 13.4 months (0.59–118.28 months). One-, 3-, and 5-year survival after recurrence were 65.2%, 34.0% and 20.5%, respectively.Multivariable Cox analysis showed that, graft from living donor (hazard ratio [HR], 0.430; 95% confidence interval [CI], 0.210–0.882; P = 0.021), recurrence-free interval of ≥9 months (HR, 0.257; 95% CI, 0.164–0.403; P < 0.001), alphafetoprotein of ≥100 ng/mL at the time of recurrence (HR, 1.689; 95% CI, 1.059–2.695; P = 0.028), and recurrence in bone (HR, 2.304; 95% CI, 1.399–3.794; P = 0.001) and everolimus within 3 months after recurrence (HR, 0.354; 95% CI, 0.141–0.889; P = 0.027) were related to survival after recurrence. @*Conclusion@#Although survival was generally poor after recurrence of hepatocellular carcinoma in liver transplantation recipients, prolonged survival can be achieved in certain patients with better prognostic factors.
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Over 30 million prescriptions of NSAIDs (non-steroidal anti-inflammatory drugs) are issued every year. Considering that these drugs are available without a prescription as over the counter (OTC) drugs, their use will be astronomical. With the increasing use of NSAIDs, their adverse effects are drawing attention. Especially, stomach bleeding, kidney toxicity, liver toxicity, and neurological toxicity are reported as common. Ibuprofen, one of the extensively used NSAIDs along with aspirin, can also induce liver toxicity, but few studies are addressing this point. Here we examined the liver toxicity of ibuprofen and investigated whether co-exposure to ethanol can manifest synergistic effects. We employed 2D and 3D cultured human hepatoma cells, HepG2 to examine the synergistic hepatotoxicity of ibuprofen and alcohol concerning cell viability, morphology, and histology of 3D spheroids. As a result, ibuprofen and alcohol provoked synergistic hepatotoxicity against hepatocytes, and their toxicity increased prominently in 3D culture upon extended exposure. Oxidative stress appeared to be the mechanisms underlying the synergistic toxicity of ibuprofen and alcohol as evidenced by increased production of ROS and expression of the endogenous antioxidant system. Collectively, this study has demonstrated that ibuprofen and EtOH can induce synergistic hepatotoxicity, providing a line of evidence for caution against the use of ibuprofen in combination with alcohol.
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Background@#Recent studies have revealed that particulate matter induces inflammation, oxidative stress, and several skin diseases. Experimental results have also shown that negative air ions are highly effective in removing particulate matter-induced inflammation. @*Objective@#The present study aimed to investigate whether negative air ions can inhibit inflammatory responses and reduce oxidative stress in HaCaT cells exposed to particulate matters. @*Methods@#HaCaT cells were treated with particulate matter in the presence or absence of negative air ions and the viability was evaluated by the MTT assay. Reactive oxygen species (ROS) generation was quantified by the dichlorodihydrofluorescein diacetate assay. The expression of genes and proteins was analyzed by real-time polymerase chain reaction and Western blot. Levels of inflammatory cytokines were quantified by enzyme-linked immunosorbent assay. @*Results@#Negative air ions were observed to downregulate the mRNA and protein levels of particulate matter-induced pro-inflammatory cytokines in HaCaT cells. In addition, negative air ion treatment suppressed particulate matter-induced intracellular ROS generation, p38 mitogen-activated protein kinase activation, and activator protein 1 (c-Fos and c-Jun) activation. @*Conclusion@#Our findings indicate that negative air ions exert anti-inflammatory and antioxidant effects in HaCaT cells exposed to particulate matter. Therefore, negative air ions can be used for the prevention and treatment of particulate matter-related inflammatory skin diseases.