1.Impaired Osteogenesis in Human Induced Pluripotent Stem Cells with Acetaldehyde Dehydrogenase 2 Mutations
Jooyoung LIM ; Heeju HAN ; Se In JUNG ; Yeri Alice RIM ; Ji Hyeon JU
International Journal of Stem Cells 2024;17(3):284-297
		                        		
		                        			
		                        			 Acetaldehyde dehydrogenase 2 (ALDH2) is the second enzyme involved in the breakdown of acetaldehyde into acetic acid during the process of alcohol metabolism. Roughly 40% of East Asians carry one or two ALDH2*2 alleles, and the presence of ALDH2 genetic mutations in individuals may affect the bone remodeling cycle owing to accumulation of acetaldehyde in the body. In this study, we investigated the effects of ALDH2 mutations on bone remodeling. In this study, we examined the effects of ALDH2 polymorphisms on in vitro osteogensis using human induced pluripotent stem cells (hiPSCs). We differentiated wild-type (ALDH2*1/*1-) and ALDH2*1/*2-genotyped hiPSCs into osteoblasts (OBs) and confirmed their OB characteristics. Acetaldehyde was administered to confirm the impact caused by the mutation during OB differentiation. Calcium deposits formed during osteogenesis were significantly decreased in ALDH2*1/*2 OBs. The expression of osteogenic markers were also decreased in acetaldehyde-treated OBs differentiated from the ALDH2*1/*2 hiPSCs. Furthermore, the impact of ALDH2 polymorphism and acetaldehyde-induced stress on inflammatory factors such as 4-hydroxynonenal and tumor necrosis factor α was confirmed. Our findings suggest that individuals with ALDH2 deficiency may face challenges in acetaldehyde breakdown, rendering them susceptible to disturbances in normal bone remodeling therefore, caution should be exercised regarding alcohol consumption. In this proof-of-concept study, we were able to suggest these findings as a result of a disease-in-a-dish concept using hiPSCs derived from individuals bearing a certain mutation. This study also shows the potential of patient-derived hiPSCs for disease modeling with a specific condition. 
		                        		
		                        		
		                        		
		                        	
2.Interfissural Fixation of the Right Middle Lobe after VideoAssisted Thoracic Surgery Right Upper Lobectomy: Bronchial Anatomical Changes and Efficacy in Preventing Torsion
Dong Jae HAN ; You Jung OK ; Se Jin OH ; Jae-Sung CHOI ; Yong Won SEONG ; Hyeon Jong MOON
Journal of Chest Surgery 2024;57(5):477-483
		                        		
		                        			 Background:
		                        			Torsion of the right middle lobe following right upper lobectomy is a rare but potentially fatal complication. To prevent this, fixation of the right middle lobe has been suggested. This study was performed to examine the impact of right middle lobe fixation on postoperative outcomes and bronchial changes. 
		                        		
		                        			Methods:
		                        			We enrolled patients who underwent curative-intent video-assisted thoracic surgery (VATS) right upper lobectomy for lung cancer from 2019 to 2022. Participants were grouped based on whether they did or did not receive right middle lobe fixation.Bronchial angles were measured using preoperative and postoperative chest computed tomography images, and postoperative outcomes and bronchial changes were compared between the 2 groups. 
		                        		
		                        			Results:
		                        			The study included a total of 50 patients, with 17 (34%) undergoing right middle lobe fixation. All procedures were performed using VATS. No significant differences between groups were observed in preoperative characteristics or postoperative outcomes.After surgery, both groups exhibited a significant increase in the right bronchus intermedius angle and a significant decrease in the branch angle. The postoperative right bronchus intermedius angle was significantly larger in the group without right middle lobe fixation compared to the group with fixation (47.38°±10.98° vs. 39.41°±9.21°, p=0.014). Three cases of atelectasis occurred in the group that did not undergo fixation while no cases were observed in the fixation group; however, this difference was not statistically significant. 
		                        		
		                        			Conclusion
		                        			Fixation of the right middle lobe reduced postoperative angulation of the right bronchus intermedius, which may help prevent postoperative atelectasis. 
		                        		
		                        		
		                        		
		                        	
3.Rituximab plus multiagent chemotherapy for newly diagnosed CD20-positive acute lymphoblastic leukemia: a prospective phase II study
Dong Won BAEK ; Han-Seung PARK ; Sang Kyun SOHN ; Dae Young KIM ; Inho KIM ; Jae-Sook AHN ; Young Rok DO ; Se Ryeon LEE ; Hyeon-Seok EOM ; Won-Sik LEE ; Sung-Hyun KIM ; Ho Sup LEE ; Yoo Jin LEE ; Joon Ho MOON ; Je-Hwan LEE ;
The Korean Journal of Internal Medicine 2023;38(5):734-746
		                        		
		                        			 Background/Aims:
		                        			We performed a prospective study to determine the efficacy and safety of rituximab including chemotherapy in CD20-positive acute lymphoblastic leukemia (ALL). 
		                        		
		                        			Methods:
		                        			Patients with newly diagnosed ALL, aged ≥ 15 years, were eligible for the study if their leukemic blast cells in bone marrow expressed CD20 ≥ 20% at the time of diagnosis. Patients received multiagent chemotherapy with rituximab. After achieving complete remission (CR), patients received five cycles of consolidation with concomitant rituximab. Rituximab was administered monthly from day 90 of transplantation for patients who received allogeneic hematopoietic cell transplantation. 
		                        		
		                        			Results:
		                        			In patients with Philadelphia (Ph)-negative ALL, 39 of 41 achieved CR (95.1%), the 2- and 4-year relapse-free survival (RFS) rates were 50.4% and 35.7%, and the 2- and 4-year overall survival (OS) rates were 51.5% and 43.2%, respectively. In the group with Ph-positive ALL, all 32 patients achieved CR, the 2- and 4-year RFS rates were 60.7% and 52.1%, and the 2- and 4-year OS rates were 73.3% and 52.3%, respectively. In the Ph-negative ALL group, patients with higher CD20 positivity experienced more favorable RFS (p < 0.001) and OS (p = 0.06) than those with lower CD20 positivity. Patients who received ≥ 2 cycles of rituximab after transplantation had significantly improved RFS (hazard ratio [HR], 0.31; p = 0.049) and OS (HR, 0.29; p = 0.021) compared with those who received < 2 cycles. 
		                        		
		                        			Conclusions
		                        			The addition of rituximab to conventional chemotherapy for CD20-positive ALL is effective and tolerable (Clinicaltrials. gov NCT01429610). 
		                        		
		                        		
		                        		
		                        	
4.Sinkihwan-gamibang ameliorates puromycin aminonucleoside-induced nephrotic syndrome.
Hyeon Kyoung LEE ; Youn Jae JANG ; Se Won NA ; Hye Yoom KIM ; Byung Hyuk HAN ; Yun Jung LEE ; Ho Sub LEE ; Jung Joo YOON ; Dae Gill KANG
Chinese Journal of Natural Medicines (English Ed.) 2022;20(3):177-184
		                        		
		                        			
		                        			Nephrotic syndrome (NS) is a kidney disease characterized by hypertriglyceridemia, massive proteinuria, hypo-albuminemia and peripheral edema. Sinkihwan-gamibang (SKHGMB) was recorded in a traditional Chinese medical book named "Bangyakhappyeon ()" and its three prescriptions Sinkihwan, Geumgwe-sinkihwan, and Jesaeng-sinkihwan belong to Gamibang. This study confirmed the effect of SKHGMB on renal dysfunction in an NS model induced by puromycin aminonucleoside (PAN). The experimental NS model was induced in male Sprague Dawley (SD) rats through injection of PAN (50 mg·kg-1)via the femoral vein. SKHGMB not only reduced the size of the kidneys increased due to PAN-induced NS, but also decreased proteinuria and ascites. In addition, SKHGMB significantly ameliorated creatinine clearance, creatinine, and blood urea nitrogen. SKHGMB relieved glomeruli dilation and tubules fibrosis in the glomeruli of the NS model. SKHGMB inhibited the protein and mRNA levels of the NLRP3 inflammasome including NLRP3, ASC, and pro-caspase-1 in NS rats. SKHGMB reduced the protein and mRNA levels of fibrosis regulators in NS rats. The results indicated that SKHGMB exerts protective effects against renal dysfunction by inhibiting of renal inflammation and fibrosis in NS rats.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Kidney
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Nephrotic Syndrome/drug therapy*
		                        			;
		                        		
		                        			Proteinuria/metabolism*
		                        			;
		                        		
		                        			Puromycin Aminonucleoside/toxicity*
		                        			;
		                        		
		                        			Rats
		                        			;
		                        		
		                        			Rats, Sprague-Dawley
		                        			
		                        		
		                        	
5.Pegfilgrastim Prophylaxis Is Effective in the Prevention of Febrile Neutropenia and Reduces Mortality in Patients Aged ≥ 75 Years with Diffuse Large B-Cell Lymphoma Treated with R-CHOP: A Prospective Cohort Study
Seong Hyun JEONG ; Seok Jin KIM ; Dok Hyun YOON ; Yong PARK ; Hye Jin KANG ; Youngil KOH ; Gyeong-Won LEE ; Won-Sik LEE ; Deok-Hwan YANG ; Young Rok DO ; Min Kyoung KIM ; Kwai Han YOO ; Yoon Seok CHOI ; Hwan Jung YUN ; Jun Ho YI ; Jae-Cheol JO ; Hyeon-Seok EOM ; Jae-Yong KWAK ; Ho-Jin SHIN ; Byeong Bae PARK ; Shin Young HYUN ; Seong Yoon YI ; Ji-Hyun KWON ; Sung Yong OH ; Hyo Jung KIM ; Byeong Seok SOHN ; Jong Ho WON ; Se-Hyung KIM ; Ho-Sup LEE ; Cheolwon SUH ; Won Seog KIM
Cancer Research and Treatment 2022;54(4):1268-1277
		                        		
		                        			 Purpose:
		                        			Febrile neutropenia (FN) can cause suboptimal treatment and treatment-related mortality (TRM) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP).  
		                        		
		                        			Materials and methods:
		                        			We conducted a prospective cohort study to evaluate the effectiveness of pegfilgrastim prophylaxis in DLBCL patients receiving R-CHOP, and we compared them with the PROCESS cohort (n=485).  
		                        		
		                        			Results:
		                        			Since January 2015, 986 patients with DLBCL were enrolled. Pegfilgrastim was administered at least once in 930 patients (94.3%), covering 90.3% of all cycles. FN developed in 137 patients (13.9%) in this cohort (23.7% in the PROCESS cohort, p<0.001), and 4.2% of all cycles (10.2% in the PROCESS cohort, p<0.001). Dose delay was less common (≥3 days: 18.1% vs. 23.7%, p=0.015; ≥5 days: 12.0% vs. 18.3%, p=0.023) in this cohort than in the PROCESS cohort. The incidence of TRM (3.2% vs. 5.6%, p=0.047) and infection-related death (1.8% vs. 4.5%, p=0.004) was lower in this cohort than in the PROCESS cohort. The 4-year overall survival (OS) and progression-free survival (PFS) rates of the two cohorts were not different (OS: 73.0% vs. 71.9%, p=0.545; PFS: 69.5% vs. 68.8%, p=0.616). However, in patients aged ≥75 years, the 4-year OS and PFS rates were higher in this cohort than in the PROCESS cohort (OS: 49.6% vs. 33.7%, p=0.032; PFS: 44.2% vs. 30.3% p=0.047).  
		                        		
		                        			Conclusion
		                        			Pegfilgrastim prophylaxis is effective in the prevention of FN and infection-related death in DLBCL patients receiving R-CHOP, and it also improves OS in patients aged ≥75 years.  
		                        		
		                        		
		                        		
		                        	
6.A Comparison of Drinking, Emotional Characteristics and Their Correlations between Patients with Alcohol Use Disorder with and without Criminal Record
Hyeon Soo JEONG ; Won Tan BYUN ; Young Min PARK ; Se Hoon KIM ; Hyun-Woo PARK ; Jae Woong JEONG ; Whi Gon KIM ; Sae Han JOO
Journal of the Korean Society of Biological Therapies in Psychiatry 2021;27(3):163-172
		                        		
		                        			 Objectives:
		                        			:In this study, socio-demographic, drinking and emotional characteristics, and their correlations were compared among patients with alcohol use disorder (AUD) according to the presence or absence of any type of criminal record. 
		                        		
		                        			Methods:
		                        			:Among patients admitted to the hospital with AUD, 27 with and 31 without criminal records were included. Socio-demographic data and drinking characteristics such as first drinking age, average daily alcohol consumption were collected. In addition, the severity of alcohol problems, the degree of change readiness for drinking alcohol, depressive symptoms, anxiety symptoms, and impulsivity were evaluated using scales and statistically analyzed. Pearson’s correlation test was applied to reveal the differences in correlation of the characteristics according to the presence or absence of criminal records. 
		                        		
		                        			Results:
		                        			:The first drinking age was significantly earlier in the AUD group with criminal records. Interestingly, the degree of change readiness regarding alcohol problem as shown in SOCRATES-K was significantly higher in the AUD group with criminal records. Anxiety symptoms were statistically significantly higher in the AUD group with criminal records. In AUD with criminal records, first drinking age negatively correlated with the degree of change readiness. In AUD without criminal records, first drinking age correlated negatively with the severity of alcohol problem, and the degree of change readiness, and the degree of change readiness negatively with age, and the degree of change readiness positively with the severity of alcohol problem. In Both groups, anxiety symptoms positively correlated with depressive symptoms. 
		                        		
		                        			Conclusions
		                        			:This study showed that AUD patients with criminal record had a faster first drinking age and the higher degree of change readiness regarding alcohol problem. Significantly higher symptoms of anxiety were also presented in AUD patients with criminal record than AUD patients who have no criminal records. Some differences were identified in correlations among characteristics between the two groups. 
		                        		
		                        		
		                        		
		                        	
7.Prognostic Value of Tumor Regression Grade on MR in Rectal Cancer: A Large-Scale, Single-Center Experience
Heera YOEN ; Hye Eun PARK ; Se Hyung KIM ; Jeong Hee YOON ; Bo Yun HUR ; Jae Seok BAE ; Jung Ho KIM ; Hyeon Jeong OH ; Joon Koo HAN
Korean Journal of Radiology 2020;21(9):1065-1076
		                        		
		                        			 Objective:
		                        			To determine the prognostic value of MRI-based tumor regression grading (mrTRG) in rectal cancer compared withpathological tumor regression grading (pTRG), and to assess the effect of diffusion-weighted imaging (DWI) on interobserveragreement for evaluating mrTRG. 
		                        		
		                        			Materials and Methods:
		                        			Between 2007 and 2016, we retrospectively enrolled 321 patients (male:female = 208:113; meanage, 60.2 years) with rectal cancer who underwent both pre-chemoradiotherapy (CRT) and post-CRT MRI. Two radiologistsindependently determined mrTRG using a 5-point grading system with and without DWI in a one-month interval. Two pathologistsgraded pTRG using a 5-point grading system in consensus. Kaplan-Meier estimation and Cox-proportional hazard models wereused for survival analysis. Cohen’s kappa analysis was used to determine interobserver agreement. 
		                        		
		                        			Results:
		                        			According to mrTRG on MRI with DWI, there were 6 mrTRG 1, 48 mrTRG 2, 109 mrTRG 3, 152 mrTRG 4, and 6 mrTRG 5.By pTRG, there were 7 pTRG 1, 59 pTRG 2, 180 pTRG 3, 73 pTRG 4, and 2 pTRG 5. A 5-year overall survival (OS) was significantlydifferent according to the 5-point grading mrTRG (p= 0.024) and pTRG (p= 0.038). The 5-year disease-free survival (DFS)was significantly different among the five mrTRG groups (p= 0.039), but not among the five pTRG groups (p= 0.072). OSand DFS were significantly different according to post-CRT MR variables: extramural venous invasion after CRT (hazard ratio= 2.259 for OS, hazard ratio = 5.011 for DFS) and extramesorectal lymph node (hazard ratio = 2.610 for DFS). For mrTRG, kvalue between the two radiologists was 0.309 (fair agreement) without DWI and slightly improved to 0.376 with DWI. 
		                        		
		                        			Conclusion
		                        			mrTRG may predict OS and DFS comparably or even better compared to pTRG. The addition of DWI on T2-weightedMRI may improve interobserver agreement on mrTRG. 
		                        		
		                        		
		                        		
		                        	
8.etection of infectious hypodermal and hematopoietic necrosis virus and white spot syndrome virus in whiteleg shrimp (Penaeus vannamei) imported from Vietnam to South Korea
Seul Chan PARK ; Seong-Kyoon CHOI ; Se-Hyeon HAN ; Song PARK ; Hye Jin JEON ; Seung Chan LEE ; Kyeong Yeon KIM ; Young Seo LEE ; Ji Hyung KIM ; Jee Eun HAN
Journal of Veterinary Science 2020;21(2):e31-
		                        		
		                        			
		                        			 n this study, whiteleg shrimp (Penaeus vannamei)  imported from Vietnam were collected from South Korean markets, and examined for 2 viruses: infectious hypodermal and hematopoietic necrosis virus (IHHNV, recently classified as decapod penstyldensovirus-1), and white spot syndrome virus (WSSV). Among 58 samples, we detected IHHNV in 23 samples and WSSV in 2 samples, using polymerase chain reaction and sequencing analyses.This is the first report of IHHNV and WSSV detection in imported shrimp, suggesting that greater awareness and stricter quarantine policies regarding viruses infecting shrimp imported to South Korea are required. 
		                        		
		                        		
		                        		
		                        	
9.Impact of Histologic Variants of Bladder Cancer on Oncology Outcome After Radical Cystectomy.
Jae Hyeon HAN ; Se Young CHOI ; Sangjun YOO ; Seung Hee BAEK ; Jeman RYU ; Yoon Soo KYUNG ; Wook NAM ; Won Chul LEE ; Dalsan YOU ; In Gab JEONG ; Bumsik HONG ; Hanjong AHN ; Choung Soo KIM
Korean Journal of Urological Oncology 2017;15(3):121-130
		                        		
		                        			
		                        			PURPOSE: To evaluate the oncological outcome of histologic variants in bladder cancer patients who underwent radical cystectomy. MATERIALS AND METHODS: We identified 393 bladder cancer patients who underwent radical cystectomy at single center between January 2007 and August 2014. Patients were divided into 4 groups according to histologic types: pure urothelial cell carcinoma (UC) and squamous, micropapillary, and other variants. Kaplan-Meier analysis was performed to assess recurrence-free (RFS) and overall survivals (OS). The patients were divided into those with pathologic stage and nodal status. RESULTS: Among 393 bladder cancer patients, squamous, micropapillary histologic variants were observed in 38 (9.7%), 26 (6.6%), respectively, whereas 39 had other variant types. Stage T3 cancer occurred in more patients with histologic variant compared with those with pure UC. Pathologic positive nodal status was also frequently found in the histologic variant groups. Subgroup analysis according to T stage and nodal status showed no significant difference in RFS and OS. On multivariate analysis, pathologic T stage (stage T2: hazard ratio [HR], 2.75; 95% confidence interval [CI], 1.34–5.63; p=0.005; stage ≥T3: HR, 3.20; 95% CI, 1.62–6.30; p=0.001) and nodal status (HR, 1.85; 95% CI, 1.05–2.56; p=0.028) were prognostic factors for RFS. CONCLUSIONS: In patients who underwent radical cystectomy, histologic variants were detected more often at advanced pathologic stage. Although histologic variants have been identified in the radical cystectomy specimen, treatment should be performed according to the pathologic stage.
		                        		
		                        		
		                        		
		                        			Cystectomy*
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Kaplan-Meier Estimate
		                        			;
		                        		
		                        			Multivariate Analysis
		                        			;
		                        		
		                        			Urinary Bladder Neoplasms*
		                        			;
		                        		
		                        			Urinary Bladder*
		                        			
		                        		
		                        	
10.Prognostic Factors for Recurrence and Progression in Korean Non-Muscle-Invasive Bladder Cancer Patients: A Retrospective, Multi-Institutional Study.
Hyung Suk KIM ; Ja Hyeon KU ; Se Joong KIM ; Sung Joon HONG ; Sung Hoo HONG ; Hong Sup KIM ; Tae Gyun KWON ; Jin Seon CHO ; Seong Soo JEON ; Kwan Joong JOO ; Han Jong AHN ; Hong Seok PARK ; Do Hwan SEONG ; Dong Deuk KWON ; Hyung Jin KIM ; Jae Sung LIM ; Hyung Lae LEE
Yonsei Medical Journal 2016;57(4):855-864
		                        		
		                        			
		                        			PURPOSE: To identify the prognostic factors related to tumor recurrence and progression in Korean patients with non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: Data were collected and analyzed for 2412 NMIBC patients from 15 centers who were initially diagnosed after transurethral resection of bladder tumor (TURBT) from January 2006 to December 2010. Using univariable and multivariable Cox proportional hazards models, the prognostic value of each variable was evaluated for the time to first recurrence and progression. RESULTS: With a median follow-up duration of 37 months, 866 patients (35.9%) experienced recurrence, and 137 (5.7%) experienced progression. Patients with recurrence had a median time to the first recurrence of 10 months. Multivariable analysis conducted in all patients revealed that preoperative positive urine cytology (PUC) was independently associated with worse recurrence-free survival [RFS; hazard ratio (HR) 1.56; p<0.001], and progression-free survival (PFS; HR 1.56; p=0.037). In particular, on multivariable analysis conducted for the high-risk group (T1 tumor/high-grade Ta tumor/carcinoma in situ), preoperative PUC was an independent predictor of worse RFS (HR 1.73; p<0.001) and PFS (HR 1.96; p=0.006). On multivariable analysis in patients with T1 high-grade (T1HG) cancer (n=684), better RFS (HR 0.75; p=0.033) and PFS (HR 0.33; p<0.001) were observed in association with the administration of intravesical Bacillus Calmette-Guérin (BCG) induction therapy. CONCLUSION: A preoperative PUC result may adversely affect RFS and PFS, particularly in high-risk NMIBC patients. Of particular note, intravesical BCG induction therapy should be administered as an adjunct to TURBT in order to improve RFS and PFS in patients with T1HG cancer.
		                        		
		                        		
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Carcinoma in Situ/*mortality/*pathology/therapy
		                        			;
		                        		
		                        			Disease Progression
		                        			;
		                        		
		                        			Disease-Free Survival
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Neoplasm Recurrence, Local/*mortality/*pathology
		                        			;
		                        		
		                        			Prognosis
		                        			;
		                        		
		                        			Proportional Hazards Models
		                        			;
		                        		
		                        			Republic of Korea
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Risk
		                        			;
		                        		
		                        			Urinary Bladder Neoplasms/*mortality/*pathology/therapy
		                        			
		                        		
		                        	
            
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