Specific sensitivity of the skin to ultraviolet B (UVB) rays is one of the mechanisms responsible for widespread skin damage. This study tested whether 1,3,5-trihydroxybenzene (THB), a compound abundant in marine products, might inhibit UVB radiationinduced NADPH oxidase 4 (NOX4) in both human HaCaT keratinocytes and mouse dorsal skin and explore its cytoprotective mechanism. The mechanism of action was determined using western blotting, immunocytochemistry, NADP + /NADPH assay, reactive oxygen species (ROS) detection, and cell viability assay. THB attenuated UVB-induced NOX4 expression both in vitro and in vivo, and suppressed UVB-induced ROS generation via NADP + production, resulting in increased cell viability with decreased apoptosis. THB also reduced the expression of UVB-induced phosphorylated AMP-activated protein kinase (AMPK) and phosphorylated c-Jun N-terminal kinase (JNK). THB suppressed UVB-induced NOX4 expression and ROS generation by inhibiting AMPK and JNK signaling pathways, thereby inhibiting cellular damage. These results showed that THB could be developed as a UV protectant.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Background: For acute ischemic stroke (AIS) patients with history of prior stroke (PS) and diabetes mellitus (DM), intravenous recombinant tissue plasminogen activator (IV-tPA) therapy in the 3- to 4.5-hour window is off-label in Korea. This study aimed to assess the safety and efficacy of IV-tPA in these patients. Methods: Using data from a prospective multicenter stroke registry between January 2009 and March 2021, we identified AIS patients who received IV-tPA in the 3- to 4.5-hour window, and compared the outcomes of symptomatic intracranial hemorrhage (SICH), 3-month mortality, 3-month modified Rankin Scale (mRS) score 0-1 and 3-month mRS distribution between patients with both PS and DM (PS/DM, n=56) versus those with neither PS nor DM, or with only one (non-PS/DM, n=927). Results: The PS/DM group versus the non-PS/DM group was more likely to have a prior disability, hypertension, hyperlipidemia, coronary heart disease and less likely to have atrial fibrillation. The PS/DM and the non-PS/DM groups had comparable rates of SICH (0% vs. 1.7%; p>0.999) and 3-month mortality (10.7% vs. 10.2%; p=0.9112). The rate of 3-month mRS 0-1 was non-significantly lower in the PS/DM group than in the non-PS/DM group (30.4% vs. 40.7%; adjusted odds ratio [95% confidence interval], 0.81 [0.41-1.59]). Conclusions In the 3- to 4.5-hour window, AIS patients with PS/DM, as compared to those with non-PS/DM, might benefit less from IV-tPA. However, given the similar risks of SICH and mortality, IV-tPA in the late time window could be considered in patients with both PS and DM.

OBJECTIVE: To analyze the complications of percutaneous transthoracic needle biopsy using CT-based imaging modalities for needle guidance in comparison with fluoroscopy in a large retrospective cohort. MATERIALS AND METHODS: This study was approved by multiple Institutional Review Boards and the requirement for informed consent was waived. We retrospectively included 10568 biopsies from eight referral hospitals from 2010 through 2014. In univariate and multivariate logistic analyses, 3 CT-based guidance modalities (CT, CT fluoroscopy, and cone-beam CT) were compared with fluoroscopy in terms of the risk of pneumothorax, pneumothorax requiring chest tube insertion, and hemoptysis, with adjustment for other risk factors. RESULTS: Pneumothorax occurred in 2298 of the 10568 biopsies (21.7%). Tube insertion was required after 316 biopsies (3.0%), and hemoptysis occurred in 550 cases (5.2%). In the multivariate analysis, pneumothorax was more frequently detected with CT {odds ratio (OR), 2.752 (95% confidence interval [CI], 2.325–3.258), p < 0.001}, CT fluoroscopy (OR, 1.440 [95% CI, 1.176–1.762], p < 0.001), and cone-beam CT (OR, 2.906 [95% CI, 2.235–3.779], p < 0.001), but no significant relationship was found for pneumothorax requiring chest tube insertion (p = 0.497, p = 0.222, and p = 0.216, respectively). The incidence of hemoptysis was significantly lower under CT (OR, 0.348 [95% CI, 0.247–0.491], p < 0.001), CT fluoroscopy (OR, 0.594 [95% CI, 0.419–0.843], p = 0.004), and cone-beam CT (OR, 0.479 [95% CI, 0.317–0.724], p < 0.001) guidance. CONCLUSION: Hemoptysis occurred less frequently with CT-based guidance modalities in comparison with fluoroscopy. Although pneumothorax requiring chest tube insertion showed a similar incidence, pneumothorax was more frequently detected using CT-based guidance modalities.
Biopsy ; Biopsy, Needle ; Chest Tubes ; Cohort Studies ; Cone-Beam Computed Tomography ; Ethics Committees, Research ; Fluoroscopy ; Hemoptysis ; Image-Guided Biopsy ; Incidence ; Informed Consent ; Lung Neoplasms ; Multivariate Analysis ; Needles ; Pneumothorax ; Referral and Consultation ; Retrospective Studies ; Risk Factors

On page 323, the grant number was incorrectly numbered as HI15C1234. The correct number is HI15C3390.

OBJECTIVE: To measure the diagnostic accuracy of percutaneous transthoracic needle lung biopsies (PTNBs) on the basis of the intention-to-diagnose principle and identify risk factors for diagnostic failure of PTNBs in a multi-institutional setting. MATERIALS AND METHODS: A total of 9384 initial PTNBs performed in 9239 patients (mean patient age, 65 years [range, 20–99 years]) from January 2010 to December 2014 were included. The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PTNBs for diagnosis of malignancy were measured. The proportion of diagnostic failures was measured, and their risk factors were identified. RESULTS: The overall accuracy, sensitivity, specificity, PPV, and NPV were 91.1% (95% confidence interval [CI], 90.6–91.7%), 92.5% (95% CI, 91.9–93.1%), 86.5% (95% CI, 85.0–87.9%), 99.2% (95% CI, 99.0–99.4%), and 84.3% (95% CI, 82.7–85.8%), respectively. The proportion of diagnostic failures was 8.9% (831 of 9384; 95% CI, 8.3–9.4%). The independent risk factors for diagnostic failures were lesions ≤ 1 cm in size (adjusted odds ratio [AOR], 1.86; 95% CI, 1.23–2.81), lesion size 1.1–2 cm (1.75; 1.45–2.11), subsolid lesions (1.81; 1.32–2.49), use of fine needle aspiration only (2.43; 1.80–3.28), final diagnosis of benign lesions (2.18; 1.84–2.58), and final diagnosis of lymphomas (10.66; 6.21–18.30). Use of cone-beam CT (AOR, 0.31; 95% CI, 0.13–0.75) and conventional CT-guidance (0.55; 0.32–0.94) reduced diagnostic failures. CONCLUSION: The accuracy of PTNB for diagnosis of malignancy was fairly high in our large-scale multi-institutional cohort. The identified risk factors for diagnostic failure may help reduce diagnostic failure and interpret the biopsy results.
Biopsy ; Biopsy, Fine-Needle ; Cohort Studies ; Cone-Beam Computed Tomography ; Diagnosis ; Humans ; Image-Guided Biopsy ; Lung Neoplasms ; Lung ; Lymphoma ; Needles ; Odds Ratio ; Risk Factors ; Sensitivity and Specificity

BACKGROUND/AIMS: Fecal calprotectin (FC) is known to correlate with disease activity and can be used as a predictor for relapse or treatment response in inflammatory bowel disease (IBD). We evaluated the usefulness of FC as a biomarker for disease activity in patients with IBD using both enzyme-linked immunosorbent assay (ELISA) and a quantitative point-of-care test (QPOCT). METHODS: Fecal samples and medical records were collected from consecutive patients with IBD. FC levels were measured by both ELISA and QPOCT and patient medical records were reviewed for clinical, laboratory, and endoscopic data. RESULTS: Ninety-three patients with IBD were enrolled, 55 with ulcerative colitis (UC) and 38 with Crohn's disease (CD). The mean FC-ELISA levels were 906.3 ± 1,484.9 μg/g in UC and 1,054.1 ± 1,252.5 μg/g in CD. There was a strong correlation between FC-ELISA level and clinical activity indices (p < 0.05). FC-ELISA level was significantly lower in patients with mucosal healing (MH) compared to those without MH in UC (85.5 ± 55.6 μg/g vs. 1,503.7 ± 2,129.9 μg/g, p = 0.005). The results from the QPOCT corresponded well to those from ELISA. A cutoff value of 201.3 μg/g for FC-ELISA and 150.5 μg/g for FC-QPOCT predicted endoscopic inflammation (Mayo endoscopic subscore ≥ 1) in UC with a sensitivity of 81.8% and 85.8%, respectively, and a specificity of 100% for both. CONCLUSIONS: FC was strongly associated with disease activity indices, serologic markers, and endoscopic activity in patients with IBD. QPOCT can be used more conveniently than ELISA to assess FC in clinical practice.
Colitis, Ulcerative ; Crohn Disease ; Enzyme-Linked Immunosorbent Assay ; Humans ; Inflammation ; Inflammatory Bowel Diseases* ; Leukocyte L1 Antigen Complex* ; Medical Records ; Point-of-Care Systems ; Recurrence ; Sensitivity and Specificity

The study of cancer in patients treated with dialysis in Korea has not been reported. The aim of this study was to investigate the incidence and mortality of cancer among patients on dialysis in Korea. The study subjects were 106 cancer patients (2.3%) out of 4,562 end-stage renal disease (ESRD) patients maintained on hemodialysis (HD) or peritoneal dialysis (PD) at Yonsei University Health System from 1996 to 2005. We excluded patients in whom the diagnosis of cancer preceded dialysis or those who received renal allograft or started dialysis after renal allograft. Seventy- three (69%) of our subjects were male and 33 (31%) were female. The mean age at the time of cancer diagnosis was 57.9+/-11.7 yr. The mean time from the start of dialysis to the diagnosis of cancer was 75.2+/-63.9 months. The most common cancer site was gastrointestinal tract (GIT) (51%) followed by urinary tract (20%), lung (8%), and thyroid (7%). Sixty nine percent of the total mortality was due to cancer. The mean time from diagnosis to death was 2.9+/-2.5 yr. In ESRD patients with cancer, there were no significant differences in mortality rates by dialysis modality. In ESRD patients, the most common cancer was GIT cancer followed by urinary tract cancer. Therefore, careful surveillance of these cancers in ESRD patients is highly recommended.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Kidney Failure, Chronic/*complications/epidemiology/*therapy ; Korea ; Male ; Middle Aged ; Neoplasms/*complications/epidemiology ; *Peritoneal Dialysis ; Registries ; *Renal Dialysis ; Time Factors

PURPOSE: Renal artery stenosis (RAS) causes or deteriorates hypertension and/or renal insufficiency, and is known as a progressive disease. The aim of this study is to reveal the change of renal function after stenting for RAS. METHODS: We retrospectively analyzed 66 patients between 1999 and 2005 who had stenting for RAS. Renal function was assessed by modified MDRD equation. According to baseline glomerular filtration rate (GFR), patients were divided into subgroups with group A (n=37, GFR > or =60 mL/min/ 1.73m2) or group B (n=29, GFR <60 mL/min/1.73m2). Clinical parameters were compared between two groups. RESULTS: A total of 66 patients (male:female=37:29) were studied. The mean age was 61+/-12 years old and the mean follow-up duration was 54+/-27 months. Sixty-one (92.4%) patients had hypertension, 20 (30.3%) had diabetes, and 48 (73%) had unilateral RAS. Group B was older than group A (65+/-9 vs. 58+/-14 years old). The mean body mass index of group B was higher than that of group A. In group A, there was a decrease in the MDRD GFR (from 75+/-11 to 70+/-15 mL/min/1.73m2; p=0.038). In contrast, in group B there was no significant change in the MDRD GFR (from 48+/-9 to 48+/-15 mL/min/1.73m2). In group A and group B, renal function has been improved in 3% and 24%, and stabilized in 70% and 52%, respectively. CONCLUSION: Stenting for RAS has renal function preserving effect in patients with renal insufficiency. Therefore, stenting should be considered as a treatment modality in RAS patients even with deteriorated renal function.
Body Mass Index ; Constriction, Pathologic ; Follow-Up Studies ; Glomerular Filtration Rate ; Humans ; Hypertension ; Renal Artery ; Renal Artery Obstruction ; Renal Insufficiency ; Retrospective Studies ; Stents

BACKGROUND/AIMS: Our study aimed to evaluate the efficacy of MMF as compared with intravenous cyclophosphamide as induction therapy for proliferative lupus nephritis in Koreans. METHODS: Forty-three patients who were diagnosed with proliferative lupus nephritis (WHO Class III and IV) between Jan 2000 and Dec 2006 were included in this study. Nineteen patients were treated with oral MMF (initial dose: 1.0 g/day and then it was increased to 2.0 g/day) and 24 patients were treated with 0.75-1.0 g/m2 of monthly intravenous cyclophosphamide (CP) followed by subsequent treatment with oral corticosteroid (initial dose 1 mg/kg/day and then it was slowly tapered down) for 6 months. The demographic and laboratory findings, the response rate and the adverse events were reviewed retrospectively and these were compared between the two groups. RESULTS: A complete response occurred in 7 out of the 19 patients (36.8%) treated with MMF and in 8 out of the 24 patients (33.3%) treated with CP, and the difference was not significantly different between the two groups (p=0.66). A partial response was achieved in 52.6% and 45.8%, respectively. There were no significant differences of the laboratory findings such as serum albumin, C3, C4, the urine protein/creatinine ratio and serum creatinine after treatment for 6 months. In addition, both groups had similar rates of adverse events. CONCLUSIONS: Our study showed that for the treatment of lupus nephritis, MMF was as effective as IV cyclophosphamide with similar adverse events. This finding suggests that MMF could be an alternative treatment for active lupus nephritis as induction therapy.
Creatinine ; Cyclophosphamide ; Humans ; Lupus Nephritis ; Mycophenolic Acid ; Retrospective Studies ; Serum Albumin