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Background Papillary breast lesions (PBLs) comprise diverse entities from benign and atypical lesions to malignant tumors. Although PBLs are characterized by a papillary growth pattern, it is challenging to achieve high diagnostic accuracy and reproducibility. Thus, we investigated the diagnostic reproducibility of PBLs in core needle biopsy (CNB) specimens with World Health Organization (WHO) classification. Methods Diagnostic reproducibility was assessed using interobserver variability (kappa value, κ) and agreement rate in the pathologic diagnosis of 60 PBL cases on CNB among 20 breast pathologists affiliated with 20 medical institutions in Korea. This analysis was performed using hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for cytokeratin 5 (CK5) and p63. The pathologic diagnosis of PBLs was based on WHO classification, which was used to establish simple classifications (4-tier, 3-tier, and 2-tier). Results On WHO classification, H&E staining exhibited ‘fair agreement’ (κ = 0.21) with a 47.0% agreement rate. Simple classifications presented improvement in interobserver variability and agreement rate. IHC staining increased the kappa value and agreement rate in all the classifications. Despite IHC staining, the encapsulated/solid papillary carcinoma (EPC/SPC) subgroup (κ = 0.16) exhibited lower agreement compared to the non-EPC/SPC subgroup (κ = 0.35) with WHO classification, which was similar to the results of any other classification systems. Conclusions Although the use of IHC staining for CK5 and p63 increased the diagnostic agreement of PBLs in CNB specimens, WHO classification exhibited a higher discordance rate compared to any other classifications. Therefore, this result warrants further intensive consensus studies to improve the diagnostic reproducibility of PBLs with WHO classification.

Abstract Background Histologic grade is the most important predictor of the clinical outcome of non-muscle invasive (Ta, T1) papillary urothelial carcinoma (NMIPUCa), but its ambiguous criteria diminish its power to predict recurrence/progression for individual patients. We attempted to find an objective and reproducible histologic predictor of NMIPUCa that correlates well with the clinical outcome. Methods A total of 296 PUCas were collected from the Departments of Surgical Pathology of 11 institutions in South Korea. The clinical outcome was grouped into no event (NE), recurrence (R), and progression (P) categories. All 25 histological parameters were numerically redefined. The clinical pathology of each case was reviewed individually by 11 pathologists from 11 institutions based on the 2004 WHO criteria and afterwards blindly evaluated by two participants, based on our proposed parameters. Univariate and multivariate logistic regression analyses were performed using the R software package. Results The level of mitoses was the most reliable parameter for predicting the clinical outcome. We propose a four-tiered grading system based on mitotic count (> 10/10 high-power fields), nuclear pleomorphism (smallest-to-largest ratio of tumor nuclei >20), presence of divergent histology, and capillary proliferation (> 20 capillary lumina per papillary core). Conclusions The level of mitoses at the initial bladder biopsy and transurethral resection (TUR) specimen appeared to be an independent predictor of the Ta PUCa outcome. Other parameters include the number of mitoses, nuclear pleomorphism, divergent histology, and capillary proliferation within the fibrovascular core. These findings may improve selection of patients for a therapeutic strategy as compared to previous grading systems.

Objective: Hairy and enhancer of split-1 (HES-1), which is a downstream target of the Notch signaling pathway, has been linked to KRAS mutations. HES-1 has been proposed as harboring oncogenic activity in colorectal cancer but has not been investigated in adenocarcinoma of the small intestine, where the drivers of oncogenesis are not as well-understood.Materials and Methods: To investigate the clinicopathologic and prognostic implications of HES-1, HES-1 immunohistochemical expression was analyzed in digital images along with clinicopathological variables, including survival and KRAS genotype, in 185 small intestinal adenocarcinomas.Results: The loss of HES-1 expression (HES-1Loss) was observed in 38.4% (71/185) of the patients, and was associated with higher pT category (P = 0.018), pancreatic invasion (P = 0.005), high grade (P = 0.043), and non-tubular histology (P = 0.004). Specifically, in tumors with mutant KRAS (KRASMT), HES-1Loss was related to proximal location (P = 0.024), high T and N categories (P = 0.005 and 0.047, respectively), and pancreatic invasion (P = 0.004). Patients with HES-1Loss showed worse overall survival compared to those with intact HES-1 (HES-1Intact) (P = 0.013). Patients with HES-1Loss/KRASMT (median, 17.3 months) had significantly worse outcomes than those with HES-1Intact/KRASWT (39.9 months), HES-1Intact/KRASMT (47.6 month), and HES-1Loss/KRASWT (36.2 months; P = 0.010). By multivariate analysis, HES-1Loss (hazard ratio = 1.55, 95% confidence interval (CI), 1.07–2.26; P = 0.022) remained an independent prognostic factor.Conclusion: HES-1expression can be used as a potential prognostic marker and may aid in the management of patients with small intestinal adenocarcinomas.

Context.--The tumor-host interaction in the tumor microenvironment (TME) affects the prognosis of patients with malignant tumors. TME assessed via tumor budding (BD) and tumor-infiltrating lymphocyte (TIL) had a prognostic impact in patients with nonampullary small intestinal and colorectal carcinomas. In ampullary carcinoma (AC), MUC5AC was recently revealed as a significant prognosticator, but studies about the TME have not been conducted. Objective.--To assess TME-based prognostic risk in AC. Design.--We generated a collective TME risk index based on high-grade BD at the invasive front (BD3) and high density of stromal-TIL (.5%) in 64 surgically resected ACs. We evaluated its predictive values for overall survival (OS) and recurrence-free survival (RFS). We also investigated the relationship of TME to MUC5AC expression. Results.--TME prognostic risk index was classified into low-risk (BDLow/TILHigh; 26 of 64; 41%), intermediate-risk (BDLow/TILLow or BDHigh/TILHigh; 23; 36%), and high-risk (BDHigh/TILLow; 15; 23%) groups. Higher TME prognostic risk was associated with higher tumor grade (P ¼ .03), lymphovascular invasion (P ¼ .05), and MUC5AC immunopositivity (P ¼ .02). TME prognostic risk index displayed better predictive ability for both OS (53.9 versus 46.1 versus 42.2) and RFS (24.8 versus 16.9 versus 15.3) than BD or TIL alone. In multivariate analysis, TME prognostic risk index was an independent prognosticator for OS (P = .003) and RFS (P = .03). Conclusions.--TME risk index in combination with BD and TIL was a stronger predictor of prognostic risk stratification than either BD or TIL alone for both OS and RFS in patients with AC. MUC5AC may modulate the interaction between tumor cells and immunity toward enhancing invasiveness in TME. [ABSTRACT FROM AUTHOR]

Abstract Direct formic acid fuel cells (DFAFCs) stand out for portable electronic devices owing to their ease of handling, abundant fuel availability, and high theoretical open circuit potential. However, the practical application of DFAFCs is hindered by the unsatisfactory performance of electrocatalysts for the sluggish anodic formic acid oxidation reaction (FAOR). Palladium (Pd) based nanomaterials have shown promise for FAOR due to their highly selective reaction mechanism, but maintaining high electrocatalytic durability remains challenging. In this study, a novel Pd‐based electrocatalyst (UiO‐Pd‐E) is reported with exceptional durability and activity for FAOR, which can be attributed to the Pd nanoparticles encapsulated within a carbon framework where concurrent chemical alloying of Pd and Zr occurs. Further, the UiO‐Pd‐E demonstrates noteworthy multifunctionality in various electrochemical reactions including electrocatalytic ethanol oxidation reaction (EOR) and oxygen reduction reaction (ORR) in addition to the FAOR, highlighting its practical potentials.

Purpose To investigate the correlation between computer-aided diagnosis (CAD) parameters in 3-tesla (T) MRI and pathologic immunohistochemical (IHC) markers in invasive carcinoma of no special type (NST). Materials and Methods A total of 94 female who were diagnosed with NST carcinoma and underwent 3T MRI using CAD, from January 2018 to April 2019, were included. The relationship between angiovolume, curve peak, and early and late profiles of dynamic enhancement from CAD with pathologic IHC markers and molecular subtypes were retrospectively investigated using Dwass, Steel, Critchlow-Fligner multiple comparison analysis, and univariate binary logistic regression analysis. Results In NST carcinoma, a higher angiovolume was observed in tumors of higher nuclear and histologic grades and in lymph node (LN) (+), estrogen receptor (ER) (-), progesterone receptor (PR) (-), human epidermal growth factor 2 (HER2) (+), and Ki-67 (+) tumors. A high rate of delayed washout and a low rate of delayed persistence were observed in Ki-67 (+) tumors. In the binary logistic regression analysis of NST carcinoma, a high angiovolume was significantly associated with a high nuclear and histologic grade, LN (+), ER (-), PR (-), HER2 (+) status, and non-luminal subtypes. A high rate of washout and a low rate of persistence were also significantly correlated with the Ki-67 (+) status. Conclusion Angiovolume and delayed washout/persistent rate from CAD parameters in contrast enhanced breast MRI correlated with predictive IHC markers. These results suggest that CAD parameters could be used as clinical prognostic, predictive factors. [ABSTRACT FROM AUTHOR]

* Context.--The roles of the gallbladder and cystic duct (CD) invasions in distal bile duct carcinoma (DBDC) have not been well elucidated. Objective.--To define the characteristics and prognostic significance of gallbladder or CD invasions in patients with DBDC. Design.--Organ invasion patterns with clinicopathologic features were assessed in 258 resected DBDCs. Results.--CD invasions (N = 31) were associated with frequent concomitant pancreatic and/or duodenal invasions (23 of 31, 74%) and showed stromal infiltration (16 of 31, 52%) and intraductal cancerization (15 of 31, 48%) patterns. In only 2 cases, invasions with intraductal cancerization were observed in the gallbladder neck. Conversely, all pancreatic (N = 175) and duodenal (83) invasions developed through stromal infiltration. CD invasions were associated with larger tumor size (P = .001), bile duct margin positivity (P = .001), perineural invasions (P = .04), and higher N categories (P = .007). Patients with pancreatic or duodenal invasions had significantly lower survival rates than those without pancreatic (median, 31.0 versus 93.9 months) or duodenal (27.5 versus 56.8 months, P < .001, both) invasions. However, those with gallbladder or CD invasions did not have different survival times (P = .13). Patients with concomitant gallbladder/CD and pancreatic/duodenal invasions demonstrated significantly lower survival rates than those without organ invasions (P < .001). Conclusions.--Gallbladder invasions were rare in DBDCs as neck invasions with intraductal cancerization. CD invasions occurred by stromal infiltrations and intraductal cancerization, whereas all pancreatic and duodenal invasions had stromal infiltration patterns. Gallbladder and/or CD invasions did not affect survival rates of patients with DBDC, while pancreatic and duodenal invasions affected survival rates. Therefore, these differences in survival rates may originate from the different invasive patterns of DBDCs. [ABSTRACT FROM AUTHOR]

Purpose To investigate the correlation of the strain elasticity of breast cancer with histologic features, immunohistochemical markers and molecular subtypes that are known to be factors related to prognosis. Materials and Methods B-mode ultrasound and strain elastography were performed in 123 patients (mean age, 53.4; range, 28–82) with invasive ductal carcinoma (IDC) (mean size, 1.54 cm; range, 0.4–7.0 cm). Histologic grade, lymph node (LN) status, lymphovascular invasion, immunohistochemical biomarkers [estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2), CK5/6, epidermal growth factor receptor, and Ki-67] and molecular subtypes were determined from surgical pathology reports. The relationships between these factors and elasticity scores were evaluated. Results LN involvement was associated with a higher elasticity score which was statistically significant (p = 0.042). The tumor size, lymphovascular invasion, histologic grades, immunohistochemical markers and molecular subtypes had no significant correlation with the elasticity score (p > 0.05 for all). However, the IDCs with larger size and a positive lymphovascular invasion tended to have higher elasticity scores. Furthermore, higher histologic grade cancers and the HER2 overexpression-type tended to have lower elasticity scores. Conclusion The elasticity score of IDC had a significant correlation with LN involvement but no statistically significant correlation with the histologic features, immunohistochemical markers or molecular subtypes. [ABSTRACT FROM AUTHOR]

Purpose T category of the eighth edition of the American Joint Committee on Cancer (AJCC) staging system for distal bile duct carcinoma (DBDC) was changed to include tumor invasion depth measurement, while the N category adopted a 3-tier classification system based on the number of metastatic nodes. Materials and Methods To validate cancer staging, a total of 200 surgically resected DBDCs were staged and compared according to the seventh and eighth editions. Results T categories included T1 (n=37, 18.5%), T2 (n=114, 57.0%), and T3 (n=49, 24.5%). N categories included N0 (n=133, 66.5%), N1 (n=50, 25.0%), and N2 (n=17, 8.5%). Stage groupings included I (n=33, 16.5%), II (n=150, 75.0%), and III (n=17, 8.5%). The overall 5-year survival rates (5-YSRs) of T1, T2, and T3 were 59.3%, 42.4%, and 12.2%, respectively. T category could discriminate patient survival by both pairwise (T1 and T2, p=0.011,T2 and T3, p < 0.001) and overall (p < 0.001) comparisons. The overall 5-YSRs of N0, N1, and N2 were 47.3%, 17.0%, and 14.7%, respectively. N category could partly discriminate patient survival by both pairwise (N0 and N1, p < 0.001,N1 and N2, p=0.579) and overall (p < 0.001) comparisons. The overall 5-YSRs of stages I, II, and III were 59.0%, 35.4%, and 14.7%, respectively. Stages could distinguish patient survival by both pairwise (I and II, p=0.002,II and III, p=0.015) and overall (p < 0.001) comparisons. On multivariate analyses, T and N categories (p=0.014 and p=0.029) and pancreatic invasion (p=0.006) remained significant prognostic factors. Conclusion The T and N categories of the eighth edition AJCC staging system for DBDC accurately predict patient prognosis. [ABSTRACT FROM AUTHOR]

Background E-cigarettes are steadily gaining popularity in Korea. However, the characteristics of e-cigarette smokers, especially nicotine dependence and stress susceptibility, have not been evaluated in comparison to those of nonsmokers or combustible cigarette smokers in Korea. Methods In this study, 28,059 participants from the Korea National Health and Nutrition Examination Survey (2013–2017) were classified into the following three groups: non-smokers, smokers (current smokers and ex-smokers of combustible cigarettes only), and e-smokers (current smokers and ex-smokers of e-cigarettes regardless of combustible cigarette use). Results Among the participants, 16,980 (60.5%), 9,247 (33.0%), and 1,832 (6.4%) subjects were non-smokers, smokers, and e-smokers, respectively. E-smokers were younger, more educated, and had a higher household income than nonsmokers or smokers. The number of e-smokers who smoked within 5 minutes of waking up (31.5% vs. 19.8%, p

ObjectiveWe aimed to evaluate the effectiveness of cervical pessary for extending twin pregnancy in women with a short cervix.MethodsBetween January 2014 and March 2019, the use of a cervical pessary for twin pregnancy in women with a cervical length of ≤15 mm was investigated between 16 and 28 weeks of gestation. We included women with a shortened cervix after a cerclage procedure and visible fetal membranes and cervical dilatation. Thirteen patients underwent pessary insertion and were matched with a control group of 15 patients. Pregnancy and neonatal outcomes were compared between the groups. We excluded women with major fetal anomalies discovered before or after birth and known placenta previa.ResultsWomen who underwent pessary insertion were diagnosed with a short cervix (0.65±0.47 vs. 0.66±0.51 cm in the pessary and control groups, respectively; P=0.957) at a gestational age similar to that of the controls (23.29 vs. 25.14 weeks, P=0.294). There was no significant difference in gestational age at delivery between them (33.29 vs. 27.29 weeks in the pessary and control groups, respectively, P=0.058). The pessary group had a longer interval between the diagnosis and delivery than the control group (60.7±28.3 vs. 22.6±24.5 days, P=0.001). The number of adverse neonatal outcomes was significantly lower in the pessary group (n=7; 28.0%) than in the control group (n=14; 58.3%; P=0.032).ConclusionThe use of a cervical pessary may prolong gestation in twin pregnancies in women with an extremely short cervix until viable gestational age.

Cigarette smoke (CS) is the major factor in the development of chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide. Furthermore, although Camellia sinensis (CN) has been known as an anti-inflammatory material, the effect of CN has not yet been known on pulmonary inflammation in COPD. Thus, we investigated the protective effects of Camellia sinensis L. extract (CLE) against pulmonary inflammation in porcine pancreas elastase (PPE) and a cigarette smoke extract (CSE)-induced COPD mouse model. Oral administration of CLE suppressed the symptoms such as infiltration of immune cells, cytokines/chemokines secretion, mucus hypersecretion, and injuries of the lung parenchyma. Increased inflammatory responses in COPD are mediated by various immune cells such as airway epithelial cells, neutrophils, and alveolar macrophages. Thus, we investigated the effect and mechanisms of CLE in H292, HL-60, and MH-S cells. The CLE inhibited the expression of IL-6, IL-8, MUC5AC and MUC5B on CSE/LPS-stimulated H292 cells and also suppressed the formation of neutrophil extracellular traps and secretion of neutrophil elastase by inhibiting reactive oxygen species in PMA-induced HL-60 cells. In particular, the CLE suppressed the release of cytokines and chemokines caused by activating the nuclear factor kappa-light-chain-enhancer of activated B via the activation of nuclear factor erythroid-2-related factor 2 and the heme oxygenase-1 pathway in CSE/LPS-stimulated MH-S cells. Therefore, we suggest that the CLE administration be the effective approach for treating or preventing chronic pulmonary diseases such as COPD induced by CS.

A fibro-osseous pseudotumor is a rare ossifying soft tissue lesion, which is thought to be a reactive rather than a neoplastic lesion, developing due to repeated trauma. The lesion mostly occurs in the subcutaneous tissue of the proximal phalanx of the digit and predominantly affects young adults, with a slight predominance in females. The clinicopathological features can mimic those of malignant soft tissue lesions, and diagnosis can be difficult. Less is known about the radiological appearance of the lesion, including magnetic resonance imaging (MRI) features, than about histological signs. Here, we report radiological findings, including MRI features, of a fibro-osseous pseudotumor of the digit in a young female. [ABSTRACT FROM AUTHOR]

Cigarette smoke (CS) is the main cause of chronic obstructive pulmonary disease (COPD), and continuous CS exposure causes lung inflammation and deterioration. To investigate the protective effects of Artemisia gmelinii against lung inflammation in this study, cigarette smoke extract (CSE)/lipopolysaccharide (LPS)-treated alveolar macrophages (AMs) and mice stimulated with CSE/porcine pancreas elastase (PPE) were used. Artemisia gmelinii ethanol extract (AGE) was effective in decreasing the levels of cytokines, chemokine, inducible nitric oxide synthase, and cyclooxygenase-2 by inhibiting mitogen-activated protein (MAP) kinases/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway in AMs. Additionally, oral administration of AGE suppressed inflammatory cells’ infiltration and secretion of inflammatory cytokines, chemokines, matrix metallopeptidase 9, and neutrophil extracellular traps in bronchoalveolar lavage fluid from the COPD model. Moreover, the obstruction of small airways, the destruction of the lung parenchyma, and expression of IL-6, TNF-α, IL-1β, and MIP-2 were suppressed by inhibiting NF-κB activation in the lung tissues of the AGE group. These effects are associated with scopolin, chlorogenic acid, hyperoside, 3,4-di-O-caffeoylquinic acid, 3,5-di-O-caffeoylquinic acid, and 4,5-di-O-caffeoylquinic acid, which are the main components of AGE. These data demonstrate the mitigation effect of AGE on lung inflammation via inhibition of MAPK and NF-κB pathways, suggesting that AGE may be instrumental in improving respiratory and lung health.

ObjectiveTo evaluate the potential effects of previous abdominal surgery on post-operative outcome and incidence of complications after total laparoscopic hysterectomy (TLH).MethodsBetween June 2008 and December 2016, 331 patients who underwent TLH were retrospectively reviewed. Participating patients were divided into 2 groups according to previous abdominal surgery. We compared the 2 groups based on estimated blood loss, operation time, hospital stay, surgery-related complications, and conversion to laparotomy rates.ResultsGroup 1 included patients without a history of abdominal surgery (n=186), group 2 included patients with a history of abdominal surgery (n=145). The complication rate was 3.2% in group 1 and 2.8% in group 2. Other post-operative outcome and complications such as estimated blood loss, hospital stay and conversion to laparotomy rates did not differ significantly between groups. Adhesiolysis was significantly more common in group 2 (P

Chronic airway exposure to harmful substances, such as deleterious gases, cigarette smoke (CS), and particulate matter, triggers chronic obstructive pulmonary disease (COPD), characterized by impaired lung function and unbridled immune responses. Emerging epigenomic and genomic evidence suggests that excessive recruitment of alveolar macrophages and neutrophils contributes to COPD pathogenesis by producing various inflammatory mediators, such as reactive oxygen species (ROS), neutrophil elastase, interleukin (IL) 6, and IL8. Recent studies showed that Epilobium species attenuated ROS, myeloperoxidase, and inflammatory cytokine production in murine and human innate immune cells. Although the Epilobium genus exerts anti-inflammatory, antioxidant, and antimicrobial effects, the question of whether the Epilobium species regulate lung inflammation and innate immune response in COPD has not been investigated. In this study, Epilobium pyrricholophum extract (EPE) suppressed inflammatory cell recruitment and clinical symptoms in porcine pancreatic elastase and CS extract-induced COPD mice. In addition, EPE attenuated inflammatory gene expression by suppressing MAPKs and NFκB activity. Furthermore, UPLC-Q-TOF MS analyses revealed the anti-inflammatory effects of the identified phytochemical constituents of EPE. Collectively, our studies revealed that EPE represses the innate immune response and inflammatory gene expression in COPD pathogenesis in mice. These findings provide insights into new therapeutic approaches for treating COPD.

Primary squamous cell carcinoma of the thyroid gland is very rare and its histogenesis is poorly defined so far. Although there have been some cases of squamous cell carcinoma with variant types of papillary thyroid carcinoma (PTC), the present case is the first primary squamous cell carcinoma with classic PTC to be reported. A 43-year-old woman presented with a 20 year history of neck mass. Neck ultrasound indicated a 6 × 4 × 3 cm large mass. The patient underwent total thyroidectomy. Histopathology indicated a well-differentiated squamous cell carcinoma and squamous metaplasia in conjunction with classic PTC. On immunohistochemistry cytokeratin 7 was positive in papillary carcinoma and squamous metaplasia, thyroglobulin was positive only in papillary carcinoma, and p63 was positive in squamous metaplasia and squamous cell carcinoma. Postoperatively, the patient received 59.4 Gy adjuvant radiotherapy, hormonal therapy and radioactive iodine therapy. At 8 months after surgery the patient remained disease free. [ABSTRACT FROM AUTHOR]

We investigated signal transducer and activator of transcription-5 (STAT5) activation status in renal cell carcinoma (RCC) and the role of transforming growth factor-β (TGF-β) in the process. Twenty normal and RCC tissues were obtained from radical nephrectomy specimens for the assessment of expressions of phosphorylated STAT5 (p-STAT5) and TGF-β1 (Western blot) and for localization and assessment of their relationship (immunohistochemical and immunofluorescence stains). By using four RCC cell lines and four primary cultured cells, the effect of TGF-β1 and/or interleukin-2 (IL-2) on the expressions of p-STAT5 were analyzed. In RCC samples, expression of p-STAT5 was significantly reduced while expression of TGF-β was enhanced compared with normal kidney tissues ( P < 0.001 and P = 0.003, respectively). P-STAT5 was observed almost exclusively in the nuclei of normal kidney tissues while TGF-β was identified in the cytoplasm of cells of both tissues reflecting the Western results. In both RCC cell lines and cells from primary cultures, treatment with TGF-β or antibody did not significantly alter STAT5 activation. However, TGF-β significantly suppressed IL-2-induced STAT5 activation, whereas anti-TGF-β antibodies enhanced IL-2-induced STAT5 further. STAT5 activation is suppressed in RCC compared with normal renal parenchyma. It may be attributed to the RCC-derived TGF-β which also interferes with IL-2-induced STAT5 pathway activation. [ABSTRACT FROM AUTHOR]

Allergic diseases, including atopic dermatitis (AD), induce type 2 helper T (Th2) cell-dominant immune responses. Miquelianin (quercetin 3-O-glucuronide, MQL) is an active compound in Rosae multiflorae fructus extract with anti-allergic properties. Here, we investigate the anti-allergic effects of MQL in an ovalbumin (OVA)-induced Th2-dominant mouse model and the associated mechanisms. Oral MQL suppressed cytokine and IL-2 production and proliferation of Th2 cells and upregulated heme oxygenase-1 (HO-1) in splenocytes. Ex vivo MQL suppressed Th1- and Th2-related immune responses by inhibiting CD4+ T cell proliferation, and upregulated HO-1 in CD4+ T cells by activating C-Raf–ERK1/2–Nrf2 pathway via induction of reactive oxygen species generation. In a trimellitic anhydride-induced AD-like mouse model, both topical and oral MQL ameliorated AD symptoms by suppressing Th2 immune responses. Our results suggest that MQL is a potential therapeutic agent for CD4+ T cell-mediated diseases, including allergic diseases.

Purpose: The purpose of this study was to identify personal, contextual, and cognitive factors influencing the career preparation behavior of Korean nursing students. In this study, an examination was done of the fitness of a path model for the relationship among these factors based on the social cognitive career theory. Methods: The participants were 413 nursing students in South Korea. Data were collected using self-report questionnaires that included self-esteem, social support, self-efficacy, outcome expectation, career decision level, and career preparation behavior. Data were analyzed using descriptive statistics, Pearson correlation analysis, and path analysis. Results: The factors influencing career preparation behavior were self-efficacy, career decision level, self-esteem, outcome expectation, and social support. The factors influencing career decision level were self-efficacy, outcome expectation, self-esteem, and social support. Conclusion: The findings indicate that self-efficacy is an important factor influencing the career behavior of Korean nursing students. Nurse educators should consider personal, contextual, and cognitive factors of nursing students and develop systemic career guidance programs to help nursing students' career preparation behavior.

Atopic dermatitis (AD) is a common inflammatory skin disease predominately related to Type 2 helper T (Th2) immune responses. In this study, we investigated whether piperine is able to improve AD symptoms using a trimellitic anhydride (TMA)-induced AD-like mouse model. Topical treatment with piperine reduced ear swelling (ear thickness and epidermal thickness) induced by TMA exposure. Furthermore, piperine inhibited pro-inflammatory cytokines such as TNF-α and IL-1β in mouse ears, compared with the TMA-induced AD group. In measuring allergic immune responses in draining lymph nodes (dLNs), we found that IL-4 secretion, GATA3 mRNA level, and STAT6 phosphorylation were suppressed by piperine treatment. In an ex vivo study, piperine also inhibited the phosphorylation of STAT6 on the CD4+ T cells isolated from splenocytes of BALB/c mice, and piperine suppressed IL-4-induced CCL26 mRNA expression and STAT6 phosphorylation in human keratinocytes resulting in the inhibition of infiltration of CCR3+ cells into inflammatory lesions. These results demonstrate that piperine could ameliorate AD symptoms through suppression of Th2-mediated immune responses, including the STAT6/GATA3/IL-4 signaling pathway. Therefore, we suggest that piperine is an excellent candidate as an inhibitor of STAT6 and may help to improve AD symptoms.

Purpose: This study was conducted to develop and test a hypothetical model to predict health outcomes in young people with type 2 diabetes. Methods: Data were collected from 190 adults aged 23–45 with type 2 diabetes mellitus who visited the endocrinology outpatient department of the two university hospitals in South Korea from November 2, 2012 to March 7, 2013. Data collection used the structured questionnaires and patient medical records. The descriptive and correlation statistics were analyzed using PASW 18.0 and structural equation modeling procedure was performed using the AMOS 18.0 program. Results: The fit of the hypothetical model was appropriate with the ratio of the chi-square statistic to degrees of freedom at 17.00, goodness-of-fit index at .975, adjusted goodness-of-fit index at .930, root mean square error of approximation at .061, normed fit index at .926, Turker-Lewis index at .929, comparative fit index at .966. Behavioral skills were a critical factor that directly affects self-management behaviors. Through behavioral skills, motivation had a statistically significant indirect effect on self-management behavior. Self-management behavior had a statistically significant direct effect on health outcome. Through self-management behavior, behavioral skills had a statistically significant indirect effect on health outcome. These variables explained 17.9% of the total variance for the health outcome in young people with type 2 diabetes. Conclusions: The results suggest that self-management behavior could be improved through nursing interventions promoting personal motivation (positive attitude), social motivation (social support), and behavioral skills (self efficacy), which can result in better health outcomes for young people with type 2 diabetes.

Background and objective Pemetrexed have been approved for the treatment of patients affected by advanced non-small cell lung cancner (NSCLC) in progression after first-line chemotherapy. We evaluated the activity and feasibility of pemetrexed in previously treated NSCLC. Methods Patients with histologically or cytologically confirmed NSCLC were evaluated from April 2007 to March 2009. The patients had relapsed or progressed after prior chemotherapy treatment. Pemetrexed (500 mg/m2) was administered intravenously once every 3 weeks after progression to prior chemotherapy. The tumor response was evaluated according to RECIST criteria by chest CT at every 2 cycles of chemotherapy. Results A total 61 patients were eligible for analysis. Performance status of them (100%) was over 2. The response rate and disease control rate were 14.7% and 37.7% respectively. Non-squamous cell carcinoma histology was significantly associated with a superior response rate (P=0.045) and disease control rate (P=0.008). The median survival time and the median progression free survival (PFS) time were 6.11 months and 2.17 months, respectively. Comparing the efficacy of pemetrexed in these two settings [second-line versus (12/61) more than third (49/61)], there was no significant difference in regard to median survival (11.18 months vs 11.46 months, P=0.922,5), but PFS was more longer in third- or further-line groups than second-line group (1.39 months vs 2.25 months, P=0.015,

Presents the case of a 20-year-old Korean man diagnosed with diffuse large B-cell lymphoma with Homer-Wright-type Rosette formation. Medical history of the patient; Results of examination by light microscopy; Immunohistochemistry technique for tumor diagnosis; Considerations in the diagnosis of soft tissue tumors.

A 81-year-old man was referred for respiratory failure by emergency medical technicians. He admitted at intensive care unit for ventilator treatment. Several hours before admission, he took sildenafil 100 mg for erectile dysfunction without prescription. The episodes of hemoptysis occurred several hours later. Computed tomography revealed multifocal diffuse ground-glass attenuation in both lungs. And the more we performed bronchoalveolar lavage, the more the color of it was turned into red. We treated him with empirical antibiotics and tranexamic acid, and hemoptysis was stopped in one day after admission. But in the 5th admission day, he died from sepsis combined with pneumonia caused by Acinetobacter baumannii abruptly.

BackgroundGallbladder cancer (GBC) has a poor prognosis. Although complete surgical resection is the only successful approach for improving survival, additional therapeutic modalities are required for recurrent or surgically unresectable GBCs.Materials and MethodsTo determine the expression status of HER2 and the mismatch repair (MMR) proteins MLH1, MSH2, MSH6, and PMS2, immunohistochemical staining of MMR proteins and HER2 was carried out in 216 surgically resected GBCs. HER2 labeling was scored by adopting a scoring system for gastric carcinomas. Tissues scoring 0 to 2+ were defined as HER2 negative, whereas those scoring 3+ were regarded as HER2-positive. In addition, silver in situ hybridization and microsatellite instability (MSI) analysis were conducted to confirm HER2 amplification and MSI, respectively.ResultsThree of 216 GBCs (1.3%) showed MMR protein deficiency. All three observed MSI cases exhibited dual loss of MSH2 and MSH6 protein expression. However, no cases showed loss of either MLH1 or PMS2 expression. No association was observed between MMR protein deficiency and other clinicopathological factors. HER2 amplification was noted in 30 (13.9%) GBCs and associated with Crohn-like lymphoid reaction (P = 0.023). No survival difference was observed based on HER2 overexpression or HER2 amplification status.ConclusionMMR protein deficiency and HER2 overexpression were observed in a small subset (1.3% and 13.9%, respectively) of GBCs without simultaneous occurrence of deficient MMR protein expression and HER2 overexpression. The presence of Crohn-like lymphoid reaction may help identify cases with HER2 amplification, by using hematoxylin-stained slides. Although the proportion of MMR protein-deficient- and HER2-overexpressing GBCs was small, applying immunotherapy to MMR protein-deficient GBCs and herceptin to HER2-overexpressing GBCs may provide alternative treatment options for patients with GBC.

Ewing sarcoma/primitive neuroectodermal tumor (ES/ PNET) most commonly occurs in the soft tissues of the extremities and the paravertebral areas. To our knowledge, no case of PNET has been reported in the gallbladder to date. We report a case of PNET of the gallbladder occur- ring in a 53-year-old woman. Microscopically, the monotonous small round cells with a formation of Homer-Wright rosettes showed intense membranous positive immunoreactivity for MIC2/CD99, as well as for neuron-specific enolase and synaptophysin. Other small round cell tumors, such as lymphoma, rhabdomyosarcoma, or melanoma, were excluded in light of negative immunoreactivity for leukocyte common antigen, desmin, and S100. The diagnosis of PNET was rendered based on the characteristic morphology and immunohistochemical findings, despite an absence of chromosomal translocations, such as t(11; 22)(q24;q12) and t(21 ;22)(q22;q12). [ABSTRACT FROM AUTHOR]

The detection of high-risk human papillomavirus (HR-HPV) is important for early diagnosis of precancerous cervical lesion. The distribution of HR-HPV genotypes in East Asia is different from that in Western countries. HR-HPVs non-16/18 including HPV-58 are highly prevalent in East Asia. Thus, a variety of HPV tests that could identify individual genotypes have been widely used. HPV 9G DNA is a deoxyribonucleic acid-based chip test, while PANArray HPV chip is a peptide nucleic acid-based array. We compared the analytic performance of these two chips for detecting and genotyping HR-HPV using 356 liquid-based cytology specimens and evaluated their diagnostic accuracies based on direct sequencing. For identifying HR-HPV, PANArray HPV and HPV 9G DNA chips agreed with each other for 85.1% of samples. Overall strength of agreement between the two tests was substantial (k = 0.68). Specifically, these two tests almost perfectly agreed for detecting several types of HR-HPV, including HPV-16, -18, -35, -52, -58, and -59 (k>0.81 for all). According to direct sequencing, PANArray HPV produced consistently higher sensitivities for detecting HR-HPV than HPV 9G DNA for either overall or individual genotypes of HR-HPV. Sensitivities and specificities for detecting HPV-58 were perfect (100%) with PANArray HPV. In conclusion, PANArray HPV is more effective than HPV 9G DNA in detecting HR-HPV. It is more useful for regions with high prevalent HPV-58 infection.

Basaloid squamous cell carcinoma (BSCC) is often founded in the head and neck region. However, BSCC in the sinonasal tract is rare. We report here on the case of a 58-yr-old woman who presented with nasal obstruction and epistaxis. Computed tomography and examination of the nasal cavity revealed a tumor mass that originated from the right inferior turbinate with erosion of the nasal floor. The tumor that was attached to the inferior turbinate, the lateral nasal wall and the eroded right side hard palate, and so all this was resected. Histopathologic examination of the excised tumor confirmed BSCC in the nasal cavity. We report here on a nasal cavity BSCC that was treated with partial maxillectomy only.

Cancer-testis antigens (CTAs) are potential targets for cancer immunotherapy. Many CTAs are located on the X chromosome and are epigenetically regulated. Loss of X chromosome inactivation (XCI) is observed in breast and ovarian cancers and is thought to be related to the overexpression of CTAs. We investigated the relation between expression of CTAs and loss of XCI in endometrial cancer.We used data generated by The Cancer Genome Atlas Genome Data Analysis Centers and data for Xist knockout mice available at the Gene Expression Omnibus.The status of XCI was estimated by methylation status, and deletion or gain of the X chromosome. The endometrial cancers were classified into the following three groups: preserved inactivated X chromosome (Xi) (n = 281), partial reactivation of Xi (n = 52), and two copies of active X group (n = 38). Loss of XCI was more common in serous adenocarcinoma. Expression of CTAs increased in endometrial cancer with loss of XCI, which was accompanied by global hypomethylation. Expression of CTAs did not increase in Xist knockout mice.Loss of XCI is common in serous adenocarcinoma. Global hypomethylation, and not loss of XCI, is the main mechanism of overexpression of CTAs.

Detecting high-risk (HR) HPV is important for clinical management of women with persistent HPV-positive and Pap-negative results. The Cobas 4800 HPV test is the first FDA-approved HPV DNA test that can be used alone as a first-line screening tool. The HPV 9G DNA chip test is a PCR-based DNA microarray assay. We evaluated the patients of consecutive HPV-positivity on HPV 9G DNA chip test without cytologic abnormalities. We then compared the performances of HPV 9G DNA chip and the Cobas 4800 HPV tests for detecting HR HPV with each other and confirmed HPV genotyping using direct sequencing. All 214 liquid-based cytology specimens were collected from 100 women with consecutive HPV-positive and Pap-negative results on the HPV 9G DNA chip test between May 2012 and Dec 2013, but only 180 specimens were available for comparing HPV test results. The HPV 9G DNA chip and the Cobas 4800 HPV tests agreed with each other in 81.7% of the samples, and the concordance rate was greater than 97.2% for detecting HPV-16 or -18. For HR genotypes other than HPV types 16 and 18, the two tests agreed for 81.1% of the samples. The sensitivity of both assays for detecting HR HPV was 100%, regardless of HR genotypes. The HPV 9G DNA chip test may be as effective as the Cobas 4800 HPV test in detecting HR HPV, and has a similar ability to identify HPV-16 and -18.