Nonparametric Bayesian modeling for hazard functions in spatial survival data

Yena Jeon,Yongku Kim 한국데이터정보과학회 2022 한국데이터정보과학회지 Vol.33 No.6

Geranylnaringenin (CG902) inhibits constitutive and inducible STAT3 activation through the activation of SHP-2 tyrosine phosphatase

Jin, Yena,Yoon, Yae Jin,Jeon, Yoon Jung,Choi, Jiyeon,Lee, Yu-Jin,Lee, Joonku,Choi, Sangho,Nash, Oyekanmi,Han, Dong Cho,Kwon, Byoung-Mog Pergamon Press 2017 Biochemical pharmacology Vol.142 No.-

<P><B>Abstract</B></P> <P>The roles and significance of signal transducer and activator of transcription 3 (STAT3) in human cancers have been extensively studied and STAT3 is a promising therapeutic target for cancer drug discovery. During the screening of natural products to identify STAT3 inhibitors, we identified geranylnaringenin (CG902), which decreased luciferase activity in a dose-dependent manner. CG902 specifically inhibited STAT3 phosphorylation at Tyr-705 in DU145 prostate cancer cells and decreased the expression levels of STAT3 target genes, such as cyclin D1, cyclin A, and survivin. Notably, the knockdown of the SHP-2 gene by small interfering RNA suppressed the ability of CG902 to inhibit STAT3 activation and CG902 activated the phosphatase activity of SHP-2 through direct interaction with SHP-2 and induced the phosphorylation of SHP-2. The interactions between CG902 and SHP-2 were confirmed by pull-down assay using biotinylated CG902. The interactions were also further validated by the drug affinity responsive target stability (DARTS) and cellular thermal shift assay (CETSA). The inhibitory effect of CG902 on cell growth was confirmed using the DU145 mouse xenograft model. We propose that CG902 inhibits STAT3 activity through a mechanism that involves the interactions between CG902 and SHP-2, and the phosphorylation of SHP-2, which leads to SHP-2 activation in DU145 cells. CG902 is the first compound to regulate STAT3 activity via the modulation of SHP-2 activity, and our results suggest that CG902 is a novel inhibitor of the STAT3 pathway and an activator of SHP-2, and may be a useful lead molecule for the development of a therapeutic STAT3 inhibitor.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

연안-해양 공간을 중심으로 한 수소경제 구현

전형모(Hyongmo Jeon),이지원(Jiwon Lee),박예나(Yena Park) 한국해양환경·에너지학회 2019 한국해양환경·에너지학회 학술대회논문집 Vol.2019 No.11

Beta-Lactam Plus Macrolide for Patients Hospitalized With Community-Acquired Pneumonia: Difference Between Autumn and Spring

Kim Yoonjung,Jeon Yena,Kwon Ki Tae,Bae Sohyun,Hwang Soyoon,Chang Hyun-Ha,Kim Shin-Woo,Lee Won Kee,Yang Ki-Hwa,Shin Ji-Hyeon,Shim Eun-Kyung 대한의학회 2022 Journal of Korean medical science Vol.37 No.45

Background: The 2017 Korean guideline on community-acquired pneumonia (CAP) recommended beta-lactam plus macrolide combination therapy for patients hospitalized with severe pneumonia, and beta-lactam monotherapy for mild-to-moderate pneumonia. However, antibiotic treatment regimen for mild-to-moderate CAP has never been evaluated for Korean patients. Methods: In this retrospective cohort study, study patients were selected from three evaluation periods (October 1 to December 31, 2014; April 1 to June 30, 2016; October 1 to December 31, 2017) of the National Quality Assessment Program for CAP management and the National Health Insurance data on the selected patients was extracted from 1 year before the first patient enrollment and 1 year after the last patient enrollment at each evaluation period for the analysis of risk adjustment and outcomes. The survival rates between beta-lactam plus macrolide (BM) groups and beta-lactam monotherapy (B) were compared using a Kaplan-Meier survival analysis after propensity score matching by age, gender, confusion, urea, respiratory rate, blood pressure at age of 65 years or older (CURB-65), and Charlson comorbidity index for risk adjustment. The differences between autumn and spring season were also evaluated. Results: A total of 30,053 patients were enrolled. Mean age and the male-to-female ratio were 64.7 ± 18.4 and 14,197:15,856, respectively. After matching, 2,397 patients in each group were analyzed. The 30-day survival rates did not differ between the BM and B groups (97.3% vs. 96.5%, P = 0.081). In patients with CURB-65 ≥ 2, the 30-day survival rate was higher in the BM than in the B group (93.7% vs. 91.0%, P = 0.044). Among patients with CURB-65 ≥ 2, the 30-day survival rate was higher in the BM than in the B group (93.3% vs. 88.5%, P = 0.009) during autumn season, which was not observed during spring (94.2% vs. 94.1%, P = 0.986). Conclusion: Beta-lactam plus macrolide combination therapy shows potential as an empirical therapy for CAP with CURB-65 ≥ 2, especially in autumn.

Elderly kidney transplant recipients have favorable outcomes but increased infection-related mortality

임정훈,Lee Ga Young,Jeon Yena,Jung Hee-Yeon,Choi Ji Young,CHO, JANG-HEE,Park Sun Hee,김용림,Kim Hyung-Kee,Huh Seung,유은상,Won Dong Il,Kim Chan-Duck 대한신장학회 2022 Kidney Research and Clinical Practice Vol.41 No.3

Background: The number of elderly patients with end-stage kidney disease has been increasing, but the outcomes of kidney transplants (KT) remain poorly understood in elderly patients. Therefore, we evaluated the clinical outcomes of elderly KT recipients and analyzed the impact of elderly donors. Methods: This retrospective cohort study included patients who underwent KT between 2000 and 2019. KT recipients were divided into four groups according to a combination of recipient and donor age (≥60 or <60 years); elderly recipients: old-to-old (n = 46) and young-to-old (n = 83); young recipients: old-to-young (n = 98) and young-to-young (n = 796). We compared the risks of mortality, graft failure, and acute rejection between groups using Cox regression analysis. Results: The incidence of delayed graft function, graft failure, and acute rejection was not different among groups. Annual mean tacrolimus trough level was not lower in elderly recipients than young recipients during 10-year follow-up. Mortality was significantly higher in elderly recipients (p = 0.001), particularly infection-related mortality (p < 0.001). In multivariable Cox regression analysis, old-toold and young-to-old groups had increased risk of mortality (adjusted hazard ratio [aHR], 2.89; 95% confidence interval [CI], 1.14– 7.32; p = 0.03; aHR, 3.06; 95% CI, 1.51–6.20; p = 0.002). However, graft failure and acute rejection risks were not increased in elderly recipients. Conclusion: In elderly recipients, graft survival and acute rejection-free survival were not inferior to those of young recipients. However, mortality, especially risk of infection-related death, was increased in elderly recipients. Thus, low immunosuppression intensity might help decrease mortality in elderly recipients.

Pretransplant C-reactive protein-to-albumin ratio predicts mortality in kidney transplant recipients: a retrospective cohort study

Kwon Jae Wan,Jeon Yena,Jung Hee-Yeon,최지영,박선희,김찬덕,김용림,Hwang Deokbi,윤우성,김형기,허승,유은상,원동일,조장희,임정훈 대한이식학회 2023 Korean Journal of Transplantation Vol.37 No.1

Background: The C-reactive protein (CRP)-to-albumin ratio (CAR) is a more effective prognostic indicator than CRP or albumin alone in various diseases. This study aimed to evaluate the predictive value of the CAR for mortality in kidney transplant recipients (KTRs). Methods: A total of 924 patients who underwent their f irst kidney transplantation at Kyungpook National University Hospital during 2006–2020 were enrolled and classified into quartile (Q) groups according to their pretransplant CAR values. A Cox regression analysis was conducted to analyze the hazard ratios (HRs) of mortality. Results: Fifty-nine patients died during the posttransplant period (mean, 85.2±44.2 months). All-cause mortality (Q1, 3.0%; Q2, 4.8%; Q3, 7.8%; Q4, 10.0%; P for trend <0.001) and infection-related mortality increased linearly with an increase in CAR (P for trend=0.004). The Q3 and Q4 had higher risks of all-cause mortality than Q1 after adjusting for confounding factors (Q3: adjusted HR [aHR] 2.49, 95% confidence interval [CI] 1.04–5.99, P=0.041; Q4: aHR 3.09, 95% CI 1.31–7.27, P=0.010). Q4 was also independently associated with infection-related mortality (aHR 5.83, 95% CI 1.27–26.8, P=0.023). The area under the curve of the CAR for all-cause and infection-related mortality was higher than that of CRP or albumin alone. There was no association between CAR and death-censored graft failure or acute rejection. Conclusions: A higher pretransplant CAR increases the risk of posttransplant mortality, particularly infection-related, in KTRs. Pretransplant CAR can be an effective and easily accessible predictor of posttransplant mortality.

Mycophenolic Acid Trough Concentration and Dose Are Associated with Hematologic Abnormalities but Not Rejection in Kidney Transplant Recipients

Jung Hee-Yeon,Lee Sukyung,Jeon Yena,Choi Ji-Young,Cho Jang-Hee,Park Sun-Hee,Kim Yong-Lim,Kim Hyung-Kee,Huh Seung,Won Dong Il,김찬덕 대한의학회 2020 Journal of Korean medical science Vol.35 No.24

Background: Little is known regarding the safe fixed dose of mycophenolic acid (MPA) for preventing biopsy-proven acute rejection (BPAR) in kidney transplant recipients (KTRs). We investigated the correlation of MPA trough concentration (MPA C0) and dose with renal transplant outcomes and adverse events. Methods: This study included 79 consecutive KTRs who received MPA with tacrolimus (TAC) and corticosteroids. The MPA C0 of all the enrolled KTRs was measured, which was determined monthly by using particle-enhanced turbidimetric inhibition immunoassay for 12 months, and clinical data were collected at each time point. The clinical endpoints included BPAR, any cytopenia, and BK or cytomegalovirus infections. Results: No differences in MPA C0 and dose were observed between KTRs with or without BPAR or viral infections under statistically comparable TAC concentrations. MPA C0 was significantly higher in patients with leukopenia (P = 0.021) and anemia (P = 0.002) compared with those without cytopenia. The MPA dose was significantly higher in patients with thrombocytopenia (P = 0.002) compared with those without thrombocytopenia. MPA C0 ≥ 3.5 µg/mL was an independent risk factor for leukopenia (adjusted odds ratio [AOR], 3.80; 95% confidence interval [CI], 1.24–11.64; P = 0.019) and anemia (AOR, 5.90; 95% CI, 1.27–27.51; P = 0.024). An MPA dose greater than the mean value of 1,188.8 mg/day was an independent risk factor for thrombocytopenia (AOR, 3.83; 95% CI, 1.15–12.78; P = 0.029). However, an MPA dose less than the mean value of 1,137.3 mg/day did not increase the risk of BPAR. Conclusion: Either a higher MPA C0 or dose is associated with an increased risk of cytopenia, but neither a lower MPA C0 nor dose is associated with BPAR within the first year of transplantation. Hence, a reduced MPA dose with TAC and corticosteroids might be safe in terms of reducing hematologic abnormalities without causing rejection.

Histopathologic and clinicopathologic classifications of antineutrophil cytoplasmic antibody-associated glomerulonephritis: a validation study in a Korean cohort

( Jeong-hoon Lim ),( Man-hoon Han ),( Yong-jin Kim ),( Yena Jeon ),( Hee-yeon Jung ),( Ji-young Choi ),( Jang-hee Cho ),( Chan-duck Kim ),( Yong-lim Kim ),( Hajeong Lee ),( Dong Ki Kim ),( Kyung Chul 대한신장학회 2021 Kidney Research and Clinical Practice Vol.40 No.1

Background: Antineutrophil cytoplasmic antibodies (ANCA)-associated glomerulonephritis (AAGN) is a common cause of rapidly progressive glomerulonephritis and requires prompt and proper immunosuppressive therapy to improve renal prognosis. This study aimed to evaluate the predictive value of two different classifications for renal outcomes in Korean AAGN patients. Methods: Ninety-two patients who were diagnosed with AAGN at two tertiary hospitals between 2004 and 2018 were retrospectively analyzed retrospectively. The histopathologic classification according to glomerular pathology and the clinicopathologic classification according to normal glomeruli ratio, degree of interstitial fibrosis/tubular atrophy, and baseline renal function were evaluated using the Cox proportional hazards model. Results: Forty-five patients (48.9%) progressed to end-stage kidney disease (ESKD) during the observation period. The mean age was 61.0 ± 15.3 years, and most patients had myeloperoxidase-ANCA (93.5%). In the histopathologic classification, the best renal survival occurred in the focal class, whereas the sclerotic class had the worst renal survival (sclerotic class vs. focal class; adjusted hazard ratio [aHR], 5.05; 95% confidence interval [CI], 1.32-19.31; p = 0.018). The mixed class had intermediate renal outcomes (mixed class vs. focal class; aHR, 4.23; 95% CI, 1.23-14.58; p = 0.022). In the clinicopathologic classification, the high-risk group had poor renal outcomes compared with the low-risk group (aHR, 6.56; 95% CI, 1.25-34.26; p = 0.026), but renal outcomes did not differ between the low- and medium-risk groups. Conclusion: In Korean AAGN patients, histopathologic and clinicopathologic classifications had predictive value for renal outcomes, especially in the sclerotic class or the high-risk group with higher risk of progression to ESKD despite treatment.

Poster Session:PS 1105 ; Gastroenterology (Gastrointestinal Tract) : Ischemic Proctitis in Patient with “Bowel Obsession Syndrome” : A Case Report

( Jun Hyung Park ),( Ji Young Park ),( Tae Joo Jeon ),( Tae Hoon Oh ),( Won Chang Shin ),( Tae Hwan Ha ),( Mi Jin Ryu ),( Seung Suk Baek ),( Yena Choi ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Ischemic proctitis is a rare clinical entity because the rectum is supplied by an extensive arterial network. In most cases of ischemic proctitis, it occurs postoperatively and often is associated with hemodynamic instability. We report here a patient diagnosed as ischemic proctitis result from unusual cause; bowel obsession syndrome. Case: A 49-year-old woman presented to the hospital with bloody stool and proctalgia for several months. She had psychiatric history of depression and obsessive compulsive disorder under treatment. From the age of 30, she had always felt fullness at the anal region and sense of obstruction with defecation, often resulting in excessive straining and need to digitally reduce the rectum to help push stool out of the rectum at least three times a day. Vital signs and laboratory test results were unremarkable. Rectal examination revealed palpable mass accompanied by tenderness. Colonoscopy showed large geographic ulcers covered with exudate and peripheral erythematous mucosa in the anterior rectal wall approximately 5 cm of the anal verge. The mucosa proximal to the ulcers was intact. Elective sigmoidoscopy 2 weeks later revealed a huge mass-like mucosa with edematous surface 5 cm above the anal verge. Histology of the biopsy specimen obtained from colonoscopy demonstrated focal loss of epithelial cells, superfi cial epithelial necrosis, destructions of vessels and thrombosis of the veins consistant with chronic ischemia. The patient was diagnosed with ischemic proctitis caused by high pressure within the rectum during defecation and persistant irritation of the rectum by enemas and fi ngers leading to mucosal ischemia. The patient received intravenously antibiotic agents and psychotherapy. She is steadily improving under long-term behavioral therapy.

Poster Session:PS 1147 ; Gastroenterology (Pancreatobilliary) : A Case of Pancreatic Adenocarcinoma Presenting as a Pancreatic Cystic Tumor

( June Min Sung ),( Ji Young Park ),( Tae Joo Jeon ),( Won Chang Shin ),( Mijin Ryu ),( Yena Choi ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Pancreatic adenocarcinoma occurs mainly in the form of a solid tumor, but when it is accompanied by cystic changes, several other conditions will have to be considered in the differential diagnosis. We present a case of a pancreatic cystic lesion accompanying pancreatic adenocarcinoma as a pseudocyst with chronic pancreatitis or mucinous cystic neoplasm (MCN). Case: A 63-year-old man presented to the hospital with left upper quadrant abdominal pain. The patient had consumed 80g of alcohol daily. On abdominal CT, a large 12cm cystic mass with peripheral enhancing wall arising from the tail of the pancreas was seen. On EUS, a huge cyst was shown well-defined unilocular lesion with an irregular solid component on the inside. EUS-guided FNA showed CEA>1000ng/mL, CA19-9>10,000U/mL and amylase 43U/L. Cytology showed the presence of atypical epithelial cells and polymorphonuclear cells; no tumor cells were observed. On history of alcohol abuse and CT fi ndings, the cystic mass was thought to be a pseudocyst with chronic pancreatitis. However, based on the fi ndings of EUS and cystic fi uid anaylsis, there was a probability that was a MCN even if MCN has a propensity to develop in women. The patient had a distal pancreatectomy, splenectomy and segmental resection of the adjacent colon. A cystic mass, 12x7 cm in size was attached to spleen and a segment of colon. On histopathological examination, the cystic mass was confi rmed to be pancreatic ductal adenocarcinoma with moderately differentiation (with cystic feature). The resection margin of pancreas was free of tumor. But the adjacent splenic capsule and colon showed the presence of malignant cells. After surgery, the patient was fi nally diagnosed as pancreatic ductal adenocarcinoma (T3N1M1, stage IV). In the fourth postoperative week, chemotherapy was initiated. The patient is currently on the treatment.